PMID- 27548512 TI - Emerging from the Unknown: Structural and Functional Features of Agnoprotein of Polyomaviruses by A. Sami Saribas, Pascale Coric, Anahit Hamazaspyan, William Davis, Rachael Axman, Martyn K. White, Magid Abou-Gharbia, Wayne Childers, Jon H. Condra, Serge Bouaziz and Mahmut Safak. PMID- 27548514 TI - The frontal executive function in exercise addicts, moderate exercisers, and exercise avoiders. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the frontal executive functions of exercise addicts, moderate exercisers, and exercise avoiders. We hypothesized that exercise addicts and avoiders would have poorer executive functions compared to moderate exercisers. METHODS: The Korean Exercise Addiction Scale was administrated to recruit participants. Electroencephalogram was recorded at the frontal scalp sites. RESULTS: The results showed that P3 and N2 latencies were shorter in the exercise addiction group than in the avoidance and moderate groups. Exercise addicts and moderate exercisers showed faster response time than exercise avoiders. DISCUSSION: P3 and N2 latencies and P3 and N2 amplitudes were discussed in terms of executive functions. SCIENTIFIC SIGNIFICANCE: This study showed that exercise addiction did not impair executive functions, but increased cognitive functioning. (Am J Addict 2016;25:466-471). PMID- 27548515 TI - Improved word comprehension in Global aphasia using a modified semantic feature analysis treatment. AB - Limited research has investigated treatment of single word comprehension in people with aphasia, despite numerous studies examining treatment of naming deficits. This study employed a single case experimental design to examine efficacy of a modified semantic feature analysis (SFA) therapy in improving word comprehension in an individual with Global aphasia, who presented with a semantically based comprehension impairment. Ten treatment sessions were conducted over a period of two weeks. Following therapy, the participant demonstrated improved comprehension of treatment items and generalisation to control items, measured by performance on a spoken word picture matching task. Improvements were also observed on other language assessments (e.g. subtests of WAB-R; PALPA subtest 47) and were largely maintained over a period of 12 weeks without further therapy. This study provides support for the efficacy of a modified SFA therapy in remediating single word comprehension in individuals with aphasia with a semantically based comprehension deficit. PMID- 27548516 TI - Substrate-Independent Growth of Atomically Precise Chiral Graphene Nanoribbons. AB - Contributing to the need for new graphene nanoribbon (GNR) structures that can be synthesized with atomic precision, we have designed a reactant that renders chiral (3,1)-GNRs after a multistep reaction including Ullmann coupling and cyclodehydrogenation. The nanoribbon synthesis has been successfully proven on different coinage metals, and the formation process, together with the fingerprints associated with each reaction step, has been studied by combining scanning tunneling microscopy, core-level spectroscopy, and density functional calculations. In addition to the GNR's chiral edge structure, the substantial GNR lengths achieved and the low processing temperature required to complete the reaction grant this reactant extremely interesting properties for potential applications. PMID- 27548517 TI - MiR-29a Regulates Radiosensitivity in Human Intestinal Cells by Targeting PTEN Gene. AB - Two major challenges encountered during radiotherapy for colorectal cancer (CRC) are radioresistance of tumor cells and damage to normal cells. An understanding of the mechanisms of radioresistance in CRC may lead to new strategies for overcoming obstacles to affective clinical therapy. In this study, the miR-29a expression was compared among four cell lines: the normal human intestinal epithelial crypt cell line, HIEC and three CRC cell lines, HT29, DLD-1 and HCT116. The roles of miR-29a in regulating cellular radiosensitivity were then investigated. The findings from this study showed that miR-29a mimic enhanced radioresistance in HIEC, HT29 and DLD-1 cells with low levels of intrinsic miR 29a. On the other hand, a miR-29a inhibitor significantly sensitized HCT116 cells with high levels of miR-29a after irradiation. Further studies indicated that PTEN was the direct functional target of miR-29a and was involved in radiosensitivity. MiR-29a could activate the PI3K/Akt signaling pathway through negatively regulated PTEN expression. In conclusion, miR-29a may regulate the radiosensitivity of intestinal cell lines by targeting the PTEN gene, which indicates miR-29a might serve as a novel approach to enhance radiosensitivity in CRC. PMID- 27548518 TI - Extrapolation Ionization Chamber Dosimetry of Fluorescent X-Ray Energies from 4.5 to 19.6 keV. AB - Characteristic X rays of energies less than approximately 20 keV are of interest in radiobiology and radiation oncology. There is evidence that these low-energy photons produce higher relative biological effectiveness (RBE) and lower oxygen enhancement ratio (OER) relative to higher energies. Lower energy X rays also offer the advantage of healthy tissue sparing beyond the target treatment depth. Electronic brachytherapy systems that can deliver characteristic and bremsstrahlung X rays of varying energy are in clinical use as well as under development. We performed low-energy extrapolation ionization chamber dosimetry using two methods: 1. the exposure-to-dose method; and 2. the Burlin theory method combined with the extrapolation chamber method of Klevenhagen. We investigated fluorescent X rays emitted from seven metals: titanium (Ti, Z = 22); chromium (Cr, Z = 24); iron (Fe, Z = 26); cobalt (Co, Z = 27); copper (Cu, Z = 29); zinc (Zn, Z = 30); and molybdenum (Mo, Z = 42). X rays were produced by irradiation of the metals with a 55 kVp, 45 mA silver anode spectrum. The data obtained were air kerma rate (cGy/min), and radiation dose rate (cGy/min) in phosphate-buffered saline (PBS) solution and water. Air kerma rates ranged from 3.55 +/- 0.10 to 14.36 +/- 0.39 cGy/min. Dose rates ranged from 3.85 +/- 0.10 to 16.96 +/- 0.46 cGy/min in PBS and 3.59 +/- 0.10 to 16.06 +/- 0.43 cGy/min in water. Dose-rate energy dependence of both models was examined by taking a ratio of measured to Monte Carlo calculated dose rates. Dosimetry method 1 exhibited a linear relationship across all energies with a slope of 0.0127 keV(-1) and R(2) of 0.9276. Method 2 exhibited a linear relationship across all energies with a slope of 0.0467 keV(-1) and R(2) of 0.9933. Method 1 or 2 may be used as a relative dosimetry system to derive dose rates to water by using a second reference ion chamber with a NIST-traceable calibration for the molybdenum spectrum. PMID- 27548519 TI - Lung-resident eosinophils represent a distinct regulatory eosinophil subset. AB - Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec 8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. PMID- 27548520 TI - Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. AB - Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus-infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ-GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH. PMID- 27548522 TI - Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis. PMID- 27548521 TI - A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution. AB - Dietary protein intake is linked to an increased incidence of type 2 diabetes (T2D). Although dietary protein dilution (DPD) can slow the progression of some aging-related disorders, whether this strategy affects the development and risk for obesity-associated metabolic disease such as T2D is unclear. Here, we determined that DPD in mice and humans increases serum markers of metabolic health. In lean mice, DPD promoted metabolic inefficiency by increasing carbohydrate and fat oxidation. In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21 expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response-driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency-induced liver NUPR1/FGF21 axis. PMID- 27548523 TI - beta1-Adrenergic receptor deficiency in ghrelin-expressing cells causes hypoglycemia in susceptible individuals. AB - Ghrelin is an orexigenic gastric peptide hormone secreted when caloric intake is limited. Ghrelin also regulates blood glucose, as emphasized by the hypoglycemia that is induced by caloric restriction in mouse models of deficient ghrelin signaling. Here, we hypothesized that activation of beta1-adrenergic receptors (beta1ARs) localized to ghrelin cells is required for caloric restriction associated ghrelin release and the ensuing protective glucoregulatory response. In mice lacking the beta1AR specifically in ghrelin-expressing cells, ghrelin secretion was markedly blunted, resulting in profound hypoglycemia and prevalent mortality upon severe caloric restriction. Replacement of ghrelin blocked the effects of caloric restriction in beta1AR-deficient mice. We also determined that treating calorically restricted juvenile WT mice with beta blockers led to reduced plasma ghrelin and hypoglycemia, the latter of which is similar to the life-threatening, fasting-induced hypoglycemia observed in infants treated with beta blockers. These findings highlight the critical functions of ghrelin in preventing hypoglycemia and promoting survival during severe caloric restriction and the requirement for ghrelin cell-expressed beta1ARs in these processes. Moreover, these results indicate a potential role for ghrelin in mediating beta blocker-associated hypoglycemia in susceptible individuals, such as young children. PMID- 27548524 TI - Reducing radiation-induced gastrointestinal toxicity - the role of the PHD/HIF axis. AB - Radiotherapy is an effective treatment strategy for cancer, but a significant proportion of patients experience radiation-induced toxicity due to damage to normal tissue in the irradiation field. The use of chemical or biological approaches aimed at reducing or preventing normal tissue toxicity induced by radiotherapy is a long-held goal. Hypoxia-inducible factors (HIFs) regulate the production of factors that may protect several cellular compartments affected by radiation-induced toxicity. Pharmacological inhibitors of prolyl hydroxylase domain-containing enzymes (PHDs), which result in stabilization of HIFs, have recently been proposed as a new class of radioprotectors. In this review, radiation-induced toxicity in the gastrointestinal (GI) tract and the main cellular compartments studied in this context will be discussed. The effects of PHD inhibition on GI radioprotection will be described in detail. PMID- 27548525 TI - A hidden residential cell in the lung. AB - Eosinophils are classically known as proinflammatory cells, as they are equipped with a variety of preformed cytotoxic mediators and have been shown to definitively contribute to asthma. The connection between eosinophils and asthma development has led to a new class of asthma therapeutics based on blocking eosinophils with humanized antibodies that neutralize IL-5, a potent eosinophil growth, activation, and survival factor. Yet, recent studies have led to an increasing appreciation that eosinophils have a variety of homeostatic functions, including immunomodulation. In this issue of the JCI, Mesnil et al. identify a notable population of lung-resident eosinophils and demonstrate that, compared with traditional eosinophils, these cells have distinct characteristics, including nuclear structure, surface markers, IL-5 independence, and immunoregulatory function that is capable of polarizing adaptive immune responses, at least in vitro. Thus, these results reinforce a key homeostatic role for this enigmatic cell population, particularly in residing and regulating immunity in the lung. PMID- 27548526 TI - Tie1: an orphan receptor provides context for angiopoietin-2/Tie2 signaling. AB - Angiopoietin-1/Tie2 (ANG1/Tie2) signaling is well documented as regulating angiogenesis and vessel maturation. This pathway is complicated by involvement of the orphan receptor Tie1, which has been implicated as both a positive and negative regulator of ANG1/Tie2 signaling, and ANG2, which can serve as both a Tie2 agonist and antagonist, depending on the context. Two papers in this issue of the JCI provide new insight into this complicated pathway. Korhonen et al. reveal that Tie1 acts to modulate the effects of ANG1 and ANG2 on Tie2 in vitro and in vivo. Kim et al. demonstrate that ANG2 acts as a Tie2 agonist in non pathological conditions, whereas in the setting of inflammation, ANG2 functions as a Tie2 antagonist and promotes vascular dysfunction. Both studies indicate that inflammation promotes cleavage of the ectodomain of Tie1 and that this cleavage event corresponds with the switch of ANG2 from a Tie2 agonist to an antagonist. The results of these studies lay the groundwork for future strategies to therapeutically exploit this pathway in diseases characterized by adverse vascular remodeling and increased permeability. PMID- 27548527 TI - BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models. AB - Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells. Mechanistically, the BET protein BRD4 directly regulated expression of the transcription factor BATF in CD8+ T cells, which was associated with differentiation of T cells into an effector memory phenotype. JQ1-treated T cells showed enhanced persistence and antitumor effects in murine T cell receptor and chimeric antigen receptor gene therapy models. Furthermore, we found that histone acetyltransferase p300 supported the recruitment of BRD4 to the BATF promoter region, and p300 inhibition similarly augmented antitumor effects of the adoptively transferred T cells. These results demonstrate that targeting the BRD4 p300 signaling cascade supports the generation of superior antitumor T cell grafts for adoptive immunotherapy. PMID- 27548528 TI - PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models. AB - Myotubular myopathy (MTM) is a devastating pediatric neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments. We have previously shown phosphatidylinositol-3-phosphate (PI3P) accumulation in animal models of MTM. Here, we tested the hypothesis that lowering PI3P levels may prevent or reverse the MTM disease process. To test this, we targeted class II and III PI3 kinases (PI3Ks) in an MTM1-deficient mouse model. Muscle-specific ablation of Pik3c2b, but not Pik3c3, resulted in complete prevention of the MTM phenotype, and postsymptomatic targeting promoted a striking rescue of disease. We confirmed this genetic interaction in zebrafish, and additionally showed that certain PI3K inhibitors prevented development of the zebrafish mtm phenotype. Finally, the PI3K inhibitor wortmannin improved motor function and prolonged lifespan of the Mtm1-deficient mice. In all, we have identified Pik3c2b as a genetic modifier of Mtm1 mutation and demonstrated that PIK3C2B inhibition is a potential treatment strategy for MTM. In addition, we set the groundwork for similar reciprocal inhibition approaches for treating other PIP metabolic disorders and highlight the importance of modifier gene pathways as therapeutic targets. PMID- 27548529 TI - Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation. AB - Angiopoietin-2 (ANG2) regulates blood vessel remodeling in many pathological conditions through differential effects on Tie2 signaling. While ANG2 competes with ANG1 to inhibit Tie2, it can paradoxically also promote Tie2 phosphorylation (p-Tie2). A related paradox is that both inactivation and overactivation of Tie2 can result in vascular remodeling. Here, we reconciled these opposing actions of ANG2 by manipulating conditions that govern its actions in the vasculature. ANG2 drove vascular remodeling during Mycoplasma pulmonis infection by acting as a Tie2 antagonist, which led to p-Tie2 suppression, forkhead box O1 (FOXO1) activation, increased ANG2 expression, and vessel leakiness. These changes were exaggerated by anti-Tie2 antibody, inhibition of PI3K signaling, or ANG2 overexpression and were reduced by anti-ANG2 antibody or exogenous ANG1. In contrast, under pathogen-free conditions, ANG2 drove vascular remodeling by acting as an agonist, promoting high p-Tie2, low FOXO1 activation, and no leakage. Tie1 activation was strong under pathogen-free conditions, but infection or TNF-alpha led to Tie1 inactivation by ectodomain cleavage and promoted the Tie2 antagonist action of ANG2. Together, these data indicate that ANG2 activation of Tie2 supports stable enlargement of normal nonleaky vessels, but reduction of Tie1 in inflammation leads to ANG2 antagonism of Tie2 and initiates a positive feedback loop wherein FOXO1-driven ANG2 expression promotes vascular remodeling and leakage. PMID- 27548531 TI - Reply to Letter: Spectral-domain optical coherence tomography as a potential biomarker in Huntington's disease. PMID- 27548530 TI - Tie1 controls angiopoietin function in vascular remodeling and inflammation. AB - The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a beta1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability. PMID- 27548532 TI - Identification of discrete epitopes of Ro52p200 and association with fetal cardiac conduction system manifestations in a rodent model. AB - Congenital heart block (CHB) is a potentially lethal condition characterized by a third-degree atrioventricular block (AVB). Despite anti-Ro52 antibodies being detected in nearly 90% of mothers of affected children, CHB occurs in only 1-2% of anti-Ro/Sjogren's-syndrome-related antigen A (SSA) autoantibody-positive pregnancies. Maternal antibodies have been suggested to bind molecules crucial to fetal cardiac function; however, it remains unknown whether a single antibody profile associates with CHB or whether several specificities and cross-reactive targets exist. Here, we aimed to define further the reactivity profile of CHB associated antibodies towards Ro52p200 (amino acid 200-239). We first analysed reactivity of a monoclonal anti-Ro52 antibody shown to induce AVB in rats (7.8C7) and of sera from anti-Ro52p200 antibody-positive mothers of children with CHB towards a panel of modified Ro52p200 peptides, and subsequently evaluated their potential to induce AVB in rats upon transfer during gestation. We observed that CHB maternal sera displayed a homogeneous reactivity profile targeting preferentially the C-terminal part of Ro52p200, in contrast to 7.8C7 that specifically bound the p200 N-terminal end. In particular, amino acid D233 appeared crucial to maternal antibody reactivity towards p200. Despite low to absent reactivity towards rat p200 and different binding profiles towards mutated rat peptides indicating recognition of different epitopes within Ro52p200, immunoglobulin (Ig)G purified from two mothers of children with CHB could induce AVB in rats. Our findings support the hypothesis that several fine antibody specificities and cross-targets may exist and contribute to CHB development in anti-Ro52 antibody-positive pregnancies. PMID- 27548533 TI - The Importance of Obligate Anaerobes and the Streptococcus anginosus Group in Pulmonary Abscess: A Clone Library Analysis Using Bronchoalveolar Lavage Fluid. AB - BACKGROUND: Appropriate antibiotic use reduces the mortality of patients with lung abscess; however, 40-60% of the bacterial etiologies in these patients have remained unknown with the culture methods. Obligate anaerobes and the Streptococcus anginosus group are common pathogens in lung abscess, but a precise evaluation of these bacteria by ordinary culture methods seems to be difficult due to upper respiratory tract contamination. OBJECTIVES: The aim of this study was to assess the microbiota of lung abscess by bronchoalveolar lavage fluid (BALF) using the molecular method in comparison to culture methods. METHODS: BALF samples obtained from the affected lesions and sputum samples of 59 patients with lung abscess were evaluated. The microbiota in BALF was analyzed according to the molecular method using the 16S ribosomal RNA gene. RESULTS: Fifty-six of the 59 BALF samples were positive in polymerase chain reaction analysis. Fusobacterium spp. (23.7%) were most frequently detected, followed by the S. anginosus group (15.3%), as the predominant phylotypes. Obligate anaerobes were detected in 42.4% of the BALF specimens as the predominant phylotypes, whereas the detection rate of obligate anaerobes was 13.6% by culture methods using BALF. In addition, the detection rate among those patients in whom the phylotype of obligate anaerobes was detected in >5% of the lung microbiota according to the molecular method was 86.5% in the 'mixed-bacterial' infection group. CONCLUSIONS: The findings by the molecular method suggest that obligate anaerobes play important roles in the pathogenesis of lung abscess and provide additional bacterial information regarding conventional culture methods. PMID- 27548535 TI - Getting Patients Walking: A Pilot Study of Mobilizing Older Adult Patients via a Nurse-Driven Intervention. AB - OBJECTIVES: To develop a system-based intervention including five components that target barriers to nurse-initiated patient ambulation. DESIGN: Pilot study of Mobilizing Older adult patients VIa a Nurse-driven intervention (MOVIN). SETTING: Twenty-six bed general medical unit. PARTICIPANTS: Nursing staff (registered nurses and certified nursing assistants) were recruited to participate in focus groups. MEASUREMENTS: Information on frequency and distance patients ambulated and nursing staff documentation of patient ambulation were retrieved from the electronic medical record. Regression discontinuity analysis was used to determine a difference between the preintervention and intervention periods in ambulation occurrence, ambulation distance, and percentage of numeric documentation of ambulation. Thematic analysis was used to analyze focus group interviews. RESULTS: A statistically significant increase in number of occurrences (t = 4.18, P = .001) and total distance (t = 2.75, P = .01) and a significantly higher positive slope in percentage of numeric documentation was found during the intervention than before the intervention. Thematic analysis identified three central categories (shifting ownership, feeling supported, making ambulation visible) that describe the effect of MOVIN on nursing staff behaviors and perceptions of the intervention. CONCLUSION: Decreasing loss of independent ambulation in hospitalized older adults requires new and innovative approaches to addressing barriers that prevent nurse-initiated patient ambulation. MOVIN is a promising system-based intervention to promoting patient ambulation and improving outcomes for hospitalized older adults. PMID- 27548536 TI - ANXIETY AND DEPRESSION DURING PREGNANCY AND TEMPERAMENT IN EARLY INFANCY: FINDINGS FROM A MULTI-ETHNIC, ASIAN, PROSPECTIVE BIRTH COHORT STUDY. AB - Maternal antenatal mood is associated with negative infant temperament. This link has not been substantiated in Asian populations. We evaluated the association between antenatal maternal mood and infant temperament among Asian mother-infant pairs. Antenatal maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987) and the State-Trait Anxiety Inventory (C. Spielberger, R. Gorsuch, R. Lushene, P. Vagg, & G. Jacobs, 1983), respectively, at 26 weeks of pregnancy and 3 months' postnatally. Infant temperament was evaluated with the Early Infant Temperament Questionnaire (B. Medoff-Cooper, W.B. Carey, & S.C. McDevitt, 1993) at 3 months. Factor analysis was performed to extract culturally relevant categories of temperamental traits. Linear regression was performed to examine the influences of antenatal maternal mood on the factor-model-derived infant temperament. Of the 609 mothers, 11% met risk criteria for depression, 17% for state-anxiety, and 19% for trait-anxiety during pregnancy. Factor analysis yielded three infant temperament factors: Emotionality and Attentional Regulation, Sensory Reactivity, and Regularity and Motor Expression, Cronbach's alphas = 0.613, 0.712, and 0.752, respectively. Maternal antenatal state-anxiety, p < .001, and trait anxiety, p = .005, were associated with negative emotionality and poor attentional regulation, especially among Chinese, whereas depression was not, p = .090. There was an association between maternal antenatal anxiety and negative infant temperamental traits in this Asian sample. PMID- 27548537 TI - Association of Ovary-Sparing Hysterectomy With Ovarian Reserve. PMID- 27548538 TI - In Reply. PMID- 27548539 TI - Umbilical Cord Venous Lactate for Predicting Arterial Lactic Acidemia and Neonatal Morbidity at Term. PMID- 27548540 TI - In Reply. PMID- 27548541 TI - From Gestational Hypertension and Preeclampsia to Atypical Hemolytic Uremic Syndrome. PMID- 27548542 TI - In Reply. PMID- 27548543 TI - Prevalence of Endometriosis During Abdominal or Laparoscopic Hysterectomy for Chronic Pelvic Pain. PMID- 27548548 TI - Practice Bulletin No 166 Summary : Thrombocytopenia in Pregnancy. AB - Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians because platelet counts are included with automated complete blood cell counts (CBCs) obtained during routine prenatal screening (1). Although most U.S. health care providers are trained using U.S. Conventional Units, most scientists, journals, and countries use Systeme International (SI) units. The laboratory results reported in U.S. Conventional Units can be converted to SI Units or vice versa by using a conversion factor. The conversion factor for platelet count results is 1.0 (ie, to convert from x 103/MUL, multiply by 1.0, to get x 109/L). Thrombocytopenia, defined as a platelet count of less than 150 x 109/L, is common and occurs in 7-12% of pregnancies (2, 3). Thrombocytopenia can result from a variety of physiologic or pathologic conditions, several of which are unique to pregnancy. Some causes of thrombocytopenia are serious medical disorders that have the potential for maternal and fetal morbidity. In contrast, other conditions, such as gestational thrombocytopenia, are benign and pose no maternal or fetal risks. Because of the increased recognition of maternal and fetal thrombocytopenia, there are numerous controversies about obstetric management of this condition. Clinicians must weigh the risks of maternal and fetal bleeding complications against the costs and morbidity of diagnostic tests and invasive interventions. PMID- 27548549 TI - Obstetric Care Consensus No 5 Summary: Severe Maternal Morbidity: Screening And Review. AB - This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review. PMID- 27548550 TI - Committee Opinion No 671 Summary: Perinatal Risks Associated With Assisted Reproductive Technology. AB - Over the past decades, the use of assisted reproductive technology (ART) has increased dramatically worldwide and has made pregnancy possible for many infertile couples. Although the perinatal risks that may be associated with ART and ovulation induction are much higher in multifetal gestations, even singletons achieved with ART and ovulation induction may be at higher risk than singletons from naturally occurring pregnancies. However, it remains unclear to what extent these associations might be related to the underlying cause(s) of infertility. Before initiating ART or ovulation induction procedures, obstetrician gynecologists and other health care providers should complete a thorough medical evaluation to ensure that patients are in good health and should counsel these women about the risks associated with treatment. Any maternal health problems or inherited conditions should be addressed. Couples at risk of passing genetic conditions on to their offspring, including those due to infertility-associated conditions, should be counseled appropriately. When a higher-order (triplet or more) multifetal pregnancy is encountered, the option of multifetal reduction should be discussed. In the case of a continuing higher-order multifetal pregnancy, ongoing obstetric care should be with an obstetrician-gynecologist or other obstetric care provider and at a facility capable of managing anticipated risks and outcomes. PMID- 27548551 TI - Committee Opinion No 672 Summary Clinical Challenges of Long-Acting Reversible Contraceptive Methods. AB - Long-acting reversible contraceptive methods are the most effective reversible contraceptives and have an excellent safety record. Although uncommon, possible long-acting reversible contraceptive complications should be included in the informed consent process. Obstetrician-gynecologists and other gynecologic care providers should understand the diagnosis and management of common clinical challenges. The American College of Obstetricians and Gynecologists recommends the algorithms included in this document for management of the most common clinical challenges. PMID- 27548552 TI - Committee Opinion No 673 Summary: Persistent Vulvar Pain. AB - Persistent vulvar pain is a complex disorder that frequently is frustrating to the patient and the clinician. It can be difficult to treat and rapid resolution is unusual, even with appropriate therapy. Vulvar pain can be caused by a specific disorder or it can be idiopathic. Idiopathic vulvar pain is classified as vulvodynia. Although optimal treatment remains unclear, consider an individualized, multidisciplinary approach to address all physical and emotional aspects possibly attributable to vulvodynia. Specialists who may need to be involved include sexual counselors, clinical psychologists, physical therapists, and pain specialists. Patients may perceive this approach to mean the practitioner does not believe their pain is "real"; thus, it is important to begin any treatment approach with a detailed discussion, including an explanation of the diagnosis and determination of realistic treatment goals. Future research should aim at evaluating a multimodal approach in the treatment of vulvodynia, along with more research on the etiologies of vulvodynia. PMID- 27548553 TI - Committee Opinion No 674 Summary: Guiding Principles for Privileging Of Innovative Procedures in Gynecologic Surgery. AB - New or emerging surgical procedures and technologies continue to be developed at a rapid rate and must be implemented safely into clinical practice. Additional privileging may be required if substantively new technical or cognitive skills are required to implement an innovative procedure or technology. Guiding principles for privileging should include cognitive and technical assessment to ensure appropriate patient selection and performance of the new procedure. Implementation also should include pertinent institutional and staff support as needed. A dynamic process for assessment and maintenance of current competency will enhance the safety of implementation and continued application of emerging procedures and technologies. The number of cases needed to demonstrate cognitive and technical proficiency will vary depending on many factors, including the health care provider's baseline expertise and technical acumen. PMID- 27548554 TI - Practice Bulletin No. 166: Thrombocytopenia in Pregnancy. AB - Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians because platelet counts are included with automated complete blood cell counts (CBCs) obtained during routine prenatal screening (). Although most U.S. health care providers are trained using U.S. Conventional Units, most scientists, journals, and countries use Systeme International (SI) units. The laboratory results reported in U.S. Conventional Units can be converted to SI Units or vice versa by using a conversion factor. The conversion factor for platelet count results is 1.0 (ie, to convert from x 103/uL, multiply by 1.0, to get x 109/L). Thrombocytopenia, defined as a platelet count of less than 150 x 109/L, is common and occurs in 7-12% of pregnancies (). Thrombocytopenia can result from a variety of physiologic or pathologic conditions, several of which are unique to pregnancy. Some causes of thrombocytopenia are serious medical disorders that have the potential for maternal and fetal morbidity. In contrast, other conditions, such as gestational thrombocytopenia, are benign and pose no maternal or fetal risks. Because of the increased recognition of maternal and fetal thrombocytopenia, there are numerous controversies about obstetric management of this condition. Clinicians must weigh the risks of maternal and fetal bleeding complications against the costs and morbidity of diagnostic tests and invasive interventions. PMID- 27548555 TI - Obstetric Care Consensus No. 5: Severe Maternal Morbidity: Screening and Review. AB - This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review. PMID- 27548556 TI - Committee Opinion No 671: Perinatal Risks Associated With Assisted Reproductive Technology. AB - Over the past decades, the use of assisted reproductive technology (ART) has increased dramatically worldwide and has made pregnancy possible for many infertile couples. Although the perinatal risks that may be associated with ART and ovulation induction are much higher in multifetal gestations, even singletons achieved with ART and ovulation induction may be at higher risk than singletons from naturally occurring pregnancies. However, it remains unclear to what extent these associations might be related to the underlying cause(s) of infertility. Before initiating ART or ovulation induction procedures, obstetrician gynecologists and other health care providers should complete a thorough medical evaluation to ensure that patients are in good health and should counsel these women about the risks associated with treatment. Any maternal health problems or inherited conditions should be addressed. Couples at risk of passing genetic conditions on to their offspring, including those due to infertility-associated conditions, should be counseled appropriately. When a higher-order (triplet or more) multifetal pregnancy is encountered, the option of multifetal reduction should be discussed. In the case of a continuing higher-order multifetal pregnancy, ongoing obstetric care should be with an obstetrician-gynecologist or other obstetric care provider and at a facility capable of managing anticipated risks and outcomes. PMID- 27548557 TI - Committee Opinion No 672: Clinical Challenges of Long-Acting Reversible Contraceptive Methods. AB - Long-acting reversible contraceptive methods are the most effective reversible contraceptives and have an excellent safety record. Although uncommon, possible long-acting reversible contraceptive complications should be included in the informed consent process. Obstetrician-gynecologists and other gynecologic care providers should understand the diagnosis and management of common clinical challenges. The American College of Obstetricians and Gynecologists recommends the algorithms included in this document for management of the most common clinical challenges. PMID- 27548558 TI - Committee Opinion No 673: Persistent Vulvar Pain. AB - Persistent vulvar pain is a complex disorder that frequently is frustrating to the patient and the clinician. It can be difficult to treat and rapid resolution is unusual, even with appropriate therapy. Vulvar pain can be caused by a specific disorder or it can be idiopathic. Idiopathic vulvar pain is classified as vulvodynia. Although optimal treatment remains unclear, consider an individualized, multidisciplinary approach to address all physical and emotional aspects possibly attributable to vulvodynia. Specialists who may need to be involved include sexual counselors, clinical psychologists, physical therapists, and pain specialists. Patients may perceive this approach to mean the practitioner does not believe their pain is "real"; thus, it is important to begin any treatment approach with a detailed discussion, including an explanation of the diagnosis and determination of realistic treatment goals. Future research should aim at evaluating a multimodal approach in the treatment of vulvodynia, along with more research on the etiologies of vulvodynia. PMID- 27548559 TI - Committee Opinion No. 674: Guiding Principles for Privileging of Innovative Procedures in Gynecologic Surgery. AB - New or emerging surgical procedures and technologies continue to be developed at a rapid rate and must be implemented safely into clinical practice. Additional privileging may be required if substantively new technical or cognitive skills are required to implement an innovative procedure or technology. Guiding principles for privileging should include cognitive and technical assessment to ensure appropriate patient selection and performance of the new procedure. Implementation also should include pertinent institutional and staff support as needed. A dynamic process for assessment and maintenance of current competency will enhance the safety of implementation and continued application of emerging procedures and technologies. The number of cases needed to demonstrate cognitive and technical proficiency will vary depending on many factors, including the health care provider's baseline expertise and technical acumen. PMID- 27548560 TI - Hit-to-Lead Optimization of a Novel Class of Potent, Broad-Spectrum Trypanosomacides. AB - The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be desired. Herein we report optimization of a novel class of N-(2 (2-phenylthiazol-4-yl)ethyl)amides, carbamates, and ureas, which rapidly, selectively, and potently kill both species of trypanosome. The mode of action of these compounds is unknown but does not involve CYP51 inhibition. They do, however, exhibit clear structure-activity relationships, consistent across both trypanosome species. Favorable physicochemical parameters place the best compounds in CNS drug-like chemical space but, as a class, they exhibit poor metabolic stability. One of the best compounds (64a) cleared all signs of T. cruzi infection in mice when CYP metabolism was inhibited, with sterile cure achieved in one mouse. This family of compounds thus shows significant promise for trypanosomiasis drug discovery. PMID- 27548561 TI - A validation of DCIS registration in a population-based breast cancer quality register and a study of treatment and prognosis for DCIS during 20 years. AB - AIMS: Sweden has a long history of population-based cancer registration. The aim of our study was to assess the validity of DCIS registration in a regional Breast Cancer Quality Register (BCQR) and to analyze trends in incidence, treatment and outcome of DCIS, over a 20-year period. MATERIAL AND METHODS: All patients with a diagnosis of primary DCIS reported in the BCQR of the Uppsala-Orebro healthcare region in Sweden 1992-2012 were included. Three hundred women were randomly selected and their medical records were compared to register data. The study period was divided into four time periods. RESULTS: A total of 2952 women were registered with a DCIS diagnosis. In the final validation cohort of 295 patients, 23 were found to have either recurrent DCIS or invasive breast cancer and eight had LCIS. The completeness and validity of key variables were 91-99%. Twenty of 31 local recurrences were registered (65%).The proportion of DCIS to all breast cancers was 9.5%. Tumor size increased over time. The frequency of mastectomy increased from 23.0% to 39.0%. The proportion of patients receiving radiotherapy after breast conserving surgery increased from 30.1% to 67.6%. The reported local recurrence rate was 9.7% after 10 years. Reported recurrences after BCS and mastectomy were 12.0 and 7.0%, respectively. The recurrence rate did not differ between women undergoing BCS with or without radiotherapy. CONCLUSION: Only 89.5% of reported DCIS was a primary pure DCIS. The completeness of primary treatment and tumor data was high. The proportion of reported local recurrences was disappointingly low, 65%. The proportion of DCIS was stable over time with a trend towards more intensified treatment. The reported recurrence rate was low independent of treatment and can reflect adequate patient selection, but also over treatment. Our results address the necessity to validate register data on a regular basis. PMID- 27548562 TI - Perception of Safety and Liking Associated to the Colour Intervention of Bike Lanes: Contribution from the Behavioural Sciences to Urban Design and Wellbeing. AB - The perception of colour and its subjective effects are key issues to designing safe and enjoyable bike lanes. This paper addresses the relationship between the colours of bike lane interventions-in particular pavement painting and intersection design-and the subjective evaluation of liking, visual saliency, and perceived safety related to such an intervention. Utilising images of three real bike lane intersections modified by software to change their colour (five in total), this study recruited 538 participants to assess their perception of all fifteen colour-design combinations. A multivariate analysis of covariance (MANCOVA) with the Bonferroni post hoc test was performed to assess the effect of the main conditions (colour and design) on the dependent variables (liking towards the intervention, level of visual saliency of the intersection, and perceived safety of the bike lane). The results showed that the colour red was more positively associated to the outcome variables, followed by yellow and blue. Additionally, it was observed that the effect of colour widely outweighs the effect of design, suggesting that the right choice and use of colour would increase the effectiveness on bike-lanes pavement interventions. Limitations and future directions are discussed. PMID- 27548563 TI - Role of gemfibrozil as an inhibitor of CYP2C8 and membrane transporters. AB - INTRODUCTION: Cytochrome P450 (CYP) 2C8 is a drug metabolizing enzyme of major importance. The lipid-lowering drug gemfibrozil has been identified as a strong inhibitor of CYP2C8 in vivo. This effect is due to mechanism-based inhibition of CYP2C8 by gemfibrozil 1-O-beta-glucuronide. In vivo, gemfibrozil is a fairly selective CYP2C8 inhibitor, which lacks significant inhibitory effect on other CYP enzymes. Gemfibrozil can, however, have a smaller but clinically meaningful inhibitory effect on membrane transporters, such as organic anion transporting polypeptide 1B1 and organic anion transporter 3. Areas covered: This review describes the inhibitory effects of gemfibrozil on CYP enzymes and membrane transporters. The clinical drug interactions caused by gemfibrozil and the different mechanisms contributing to the interactions are reviewed in detail. Expert opinion: Gemfibrozil is a useful probe inhibitor of CYP2C8 in vivo, but its effect on membrane transporters has to be taken into account in study design and interpretation. Moreover, gemfibrozil could be used to boost the pharmacokinetics of CYP2C8 substrate drugs. Identification of gemfibrozil 1-O beta-glucuronide as a potent mechanism-based inhibitor of CYP2C8 has led to recognition of glucuronide metabolites as perpetrators of drug-drug interactions. Recently, also acyl glucuronide metabolites of clopidogrel and deleobuvir have been shown to strongly inhibit CYP2C8. PMID- 27548564 TI - Factors Associated With Neurological Outcome After Childhood Stroke-Reply. PMID- 27548566 TI - Intramolecular Photocycloaddition Reactions of Arylcyclopropane Tethered 1 Cyanonaphthalenes. AB - Intramolecular photocycloaddition reactions of 1-cyanonaphthalenes bearing an arylcyclopropane containing side chain were investigated. Photoreactions of members of this family in which the arylcyclopropane moiety is bonded at the 2 position of the 1-cyanonaphthalene ring produce head-to-head and head-to-tail 1,2 [3+2] photocycloadducts. On the other hand, substances in this family containing an arylcyclopropane side chain linked to the 4-position of the cyanoarene ring undergo photoreactions to form [4+3] photocycloadducts along with novel nine membered ring products, which are produced by photochemically induced 10pi conrotatory ring opening of the initially formed intramolecular [3+2] cycloadducts. The results of solvent effects and fluorescence investigations along with those focusing on corresponding intermolecular photoreactions demonstrate that the photocycloadducts are formed predominantly through an intramolecular exciplex mechanism and that a photoinduced intramolecular electron transfer pathway via zwitterionic biradicals might be partly responsible for the process when CH3CN is the solvent. PMID- 27548567 TI - Branching Analysis of Multivalent Conjugates Using Size Exclusion Chromatography Multiangle Light Scattering. AB - Multivalent conjugates (MVCs) (conjugation of multiple proteins to a linear polymer chain) are powerful for improving the bioactivity and pharmacokinetics of a bioactive molecule. Since this effect is highly dependent upon the valency of the conjugated proteins, it is imperative to have a technique for analysis of the conjugation ratio. Studies of MVCs have used size exclusion chromatography multiangle light scattering (SEC-MALS), which allows for the separate and individual analysis of the protein and biopolymer components based on their specific refractive index increment and UV extinction coefficient constants to determine the number of proteins bound per biopolymer molecule. In this work, we have applied traditional branching analysis to the SEC-MALS data, with the primary assumption that the polymer backbone can be used as the linear counterpart. We demonstrated good agreement between the branching values and the valency determined by traditional analysis, demonstrating that branching analysis can be used as an alternative technique to approximate the valency of MVCs. The branching analysis method also provides a more complete picture of the distribution of the measured values, provides important branching information about the molecules, and lowers the cost and complexity of the characterization. However, since MVC molecules are both conjugate molecules and branched molecules, the most powerful approach to their characterization would be to use both traditional multivalent conjugate analysis and branching analysis in conjunction. PMID- 27548565 TI - H3K36 methyltransferases as cancer drug targets: rationale and perspectives for inhibitor development. AB - Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark regulating gene transcription, alternative splicing and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Structural studies of the catalytic SET domain of H3K36 KMTases have revealed intriguing opportunities for design of small molecule inhibitors. Nevertheless, potent inhibitors for most H3K36 KMTases have not yet been developed, underlining the challenges associated with this target class. As we now have strong evidence linking H3K36 KMTases to cancer, drug development efforts are predicted to yield novel compounds in the near future. PMID- 27548568 TI - Validation of Protein Knockout in Mutant Zebrafish Lines Using In Vitro Translation Assays. AB - Advances in genome-editing technology have made creation of zebrafish mutant lines accessible to the community. Experimental validation of protein knockout is a critical step in verifying null mutants, but this can be a difficult task. Absence of protein can be confirmed by Western blotting; however, this approach requires target-specific antibodies that are generally not available for zebrafish proteins. We address this issue using in vitro translation assays, a fast and standard procedure that can be easily implemented. PMID- 27548569 TI - Pressure Tuning of First Dimension Columns in Comprehensive Two-Dimensional Gas Chromatography. AB - The experimental approach and mechanism of pressure tuning (PT) are introduced for the first stage of a comprehensive two-dimensional gas chromatography (GC * GC) separation. The PT-GC * GC system incorporates a first dimension ((1)D) coupled column ensemble comprising a pair of (1)D columns ((1)D1 and (1)D2) connected via a microfluidic splitter device, allowing variable decompression of carrier gas across each (1)D column, and a conventional (2)D narrow bore column. By variation of junction pressure between the (1)D1 and (1)D2 columns, tunable total (1)D retentions of analytes are readily derived. Separations of a standard mixture comprising a number of different chemical classes (including alkanes, monoaromatics, alcohols, aldehydes, ketones, and esters) and Australian tea tree oil (TTO) were studied as practical examples of the PT-GC * GC system application. This illustrated the change of analyte retention time with experimental conditions depending on void time and retention on the different columns. In addition to void time change, variation of carrier gas relative decompression in the (1)D ensemble leads to tunable contribution of the (1)D1/(1)D2 columns that changes apparent polarity and selectivity of the ensemble. The resulting changes in (1)D elution order further altered elution temperature and thus retention of each analyte on the (2)D column in temperature programmed GC * GC. 2D orthogonality measurements were then conducted to evaluate overall separation performance under application of different (1)D junction pressure. As a result, distribution and selectivity of particular target compounds, monoterpenes, sesquiterpenes, and oxygenated terpenes in 2D space, and thus orthogonality, could be adequately tuned. This indicates the potential of PT GC * GC to be applicable for practical sample separation and provides a general approach to tune selectivity of target compounds. PMID- 27548570 TI - The safety and tolerability of the second-line injectable antituberculosis drugs in children. AB - INTRODUCTION: A growing number of children globally are being treated for multidrug-resistant tuberculosis (MDR-TB). The second-line injectable antituberculosis medications amikacin, kanamycin and capreomycin, traditionally a mainstay of MDR-TB treatment, cause important adverse effects including permanent sensorineural hearing loss, nephrotoxicity, electrolyte abnormalities, injection pain and local injection site complications. Areas covered: To characterize the safety and tolerability of the second-line injectables in children treated for MDR-TB, we reviewed data on the mechanism of injectable associated adverse effects, risk factors for their development, and the incidence of injectable associated adverse effects in adults and children treated for MDR-TB. Expert opinion: Despite a substantial evidence base in adults demonstrating the frequent and potentially serious adverse effects of second-line injectables, important knowledge gaps remain. Improved characterization of the incidence of injectable associated adverse effects will inform rational guidance on monitoring children with TB on injectables. Eliminating the need for injectables in MDR-TB treatment regimens is a high priority, and will rely on the use of novel antituberculosis TB drugs. Strategies to reduce the risk of adverse effects of injectables, if used, deserve evaluation. This includes evaluation of potentially otoprotective medications N-acetylcysteine or aspirin, high frequency hearing screening for earlier detection of ototoxicity and therapeutic drug monitoring. PMID- 27548571 TI - A Comparison of Mortality Following Emergency Laparotomy Between Populations From New York State and England. AB - OBJECTIVE: The aim of this study was to compare mortality following emergency laparotomy between populations from New York State and England. SUMMARY OF BACKGROUND DATA: Mortality following emergency surgery is a key quality improvement metric in both the United States and UK. Comparison of the all-cause 30-day mortality following emergency laparotomy between populations from New York State and England might identify factors that could improve care. METHODS: Patient demographics, in-hospital, and 30-day outcomes data were extracted from Hospital Episode Statistics (HES) in England and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients older than 18 years undergoing laparotomy for emergency open bowel surgery between April 2009 and March 2014. The primary outcome measure was all cause mortality within 30 days of the index laparotomy. Mixed-effects logistic regression was performed to model independent demographic variables against mortality. A one-to-one propensity score matched dataset was created to compare the odd ratios of mortality between the 2 populations. RESULTS: Overall, 137,869 patient records, 85,286 (61.9%) from England and 52,583 (38.1%) from New York State, were extracted. Crude 30-day mortality for patients was significantly higher in the England compared with New York State [11,604 (13.6%) vs 3633 (6.9%) patients, P < 0.001]. Patients undergoing emergency laparotomy in England had significantly higher risk of mortality compared with those in New York State (odds ratio 2.35, confidence interval 2.24-2.46, P < 0.001). CONCLUSION: The risk of mortality at 30 days is higher following emergency laparotomy in England as compared with New York State despite similar patient groups. PMID- 27548572 TI - Hydration Dynamics of a Peripheral Membrane Protein. AB - Water dynamics in the hydration shell of the peripheral membrane protein annexin B12 were studied using MD simulations and Overhauser DNP-enhanced NMR. We show that retardation of water motions near phospholipid bilayers is extended by the presence of a membrane-bound protein, up to around 10 A above that protein. Near the membrane surface, electrostatic interactions with the lipid head groups strongly slow down water dynamics, whereas protein-induced water retardation is weaker and dominates only at distances beyond 10 A from the membrane surface. The results can be understood from a simple model based on additive contributions from the membrane and the protein to the activation free energy barriers of water diffusion next to the biomolecular surfaces. Furthermore, analysis of the intermolecular vibrations of the water network reveals that retarded water motions near the membrane shift the vibrational modes to higher frequencies, which we used to identify an entropy gradient from the membrane surface toward the bulk water. Our results have implications for processes that take place at lipid membrane surfaces, including molecular recognition, binding, and protein protein interactions. PMID- 27548573 TI - Medication Review After a Fracture-Absolutely Essential. PMID- 27548574 TI - Estimation of an accuracy index of a diagnostic biomarker when the reference biomarker is continuous and measured with error. AB - New biomarkers continue to be developed for the purpose of diagnosis, and their diagnostic performances are typically compared with an existing reference biomarker used for the same purpose. Considerable amounts of research have focused on receiver operating characteristic curves analysis when the reference biomarker is dichotomous. In the situation where the reference biomarker is measured on a continuous scale and dichotomization is not practically appealing, an index was proposed in the literature to measure the accuracy of a continuous biomarker, which is essentially a linear function of the popular Kendall's tau. We consider the issue of estimating such an accuracy index when the continuous reference biomarker is measured with errors. We first investigate the impact of measurement errors on the accuracy index, and then propose methods to correct for the bias due to measurement errors. Simulation results show the effectiveness of the proposed estimator in reducing biases. The methods are exemplified with hemoglobin A1c measurements obtained from both the central lab and a local lab to evaluate the accuracy of the mean data obtained from the metered blood glucose monitoring against the centrally measured hemoglobin A1c from a behavioral intervention study for families of youth with type 1 diabetes. PMID- 27548575 TI - Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. AB - Cerebral cavernous malformations (CCMs) are vascular malformations that affect the central nervous system and result in cerebral hemorrhage, seizure and stroke. CCMs arise from loss-of-function mutations in one of three genes: KRIT1 (also known as CCM1), CCM2 or PDCD10 (also known as CCM3). PDCD10 mutations in humans often result in a more severe form of the disease relative to mutations in the other two CCM genes, and PDCD10-knockout mice show severe defects, the mechanistic basis for which is unclear. We have recently reported that CCM3 regulates exocytosis mediated by the UNC13 family of exocytic regulatory proteins. Here, in investigating the role of endothelial cell exocytosis in CCM disease progression, we found that CCM3 suppresses UNC13B- and vesicle-associated membrane protein 3 (VAMP3)-dependent exocytosis of angiopoietin 2 (ANGPT2) in brain endothelial cells. CCM3 deficiency in endothelial cells augments the exocytosis and secretion of ANGPT2, which is associated with destabilized endothelial cell junctions, enlarged lumen formation and endothelial cell pericyte dissociation. UNC13B deficiency, which blunts ANGPT2 secretion from endothelial cells, or treatment with an ANGPT2-neutralizing antibody normalizes the defects in the brain and retina caused by endothelial-cell-specific CCM3 deficiency, including the disruption of endothelial cell junctions, vessel dilation and pericyte dissociation. Thus, enhanced secretion of ANGPT2 in endothelial cells contributes to the progression of CCM disease, providing a new therapeutic approach for treating this devastating pathology. PMID- 27548576 TI - 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice. AB - Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A-APC (Lys191 193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic and reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes and lethal body radiation. On the basis of proof-of-concept studies and an excellent safety profile in humans, 3K3A-APC has advanced to clinical trials as a neuroprotectant in ischemic stroke. Recently, 3K3A-APC has been shown to stimulate neuronal production by human neural stem and progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1 phosphate-receptor 1-Akt pathway, which suggests the potential for APC-based treatment as a strategy for structural repair in the human central nervous (CNS) system. Here we report that late postischemic treatment of mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration and improves functional recovery. Thus, 3K3A-APC-potentiated neuronal recruitment from engrafted NSCs might offer a new approach to the treatment of stroke and related neurological disorders. PMID- 27548577 TI - The contribution of posttraumatic stress disorder and mild traumatic brain injury to persistent post concussive symptoms following motor vehicle accidents. AB - OBJECTIVE: Persistent postconcussive symptoms (PPCS) are a set of physical, cognitive, emotional, and behavioral symptoms that often follow mild traumatic brain injury (mTBI). Some of these symptoms also occur in posttraumatic stress disorder (PTSD). The current study examined the unique contribution of mTBI and PTSD to PPCS. The roles of neurocognitive and motivational factors were also addressed. METHOD: Sixty one children and adolescents (ages 6-18), at least 3 months post motor vehicle accident (MVA), participated in the study. All participants were diagnosed with PTSD symptoms. Thirty three participants met mTBI criteria, and 28 did not. Standard instruments for assessment included a semistructured clinical interview, self-report questionnaires, and a neuropsychological evaluation. RESULTS: No differences were found between the mTBI and non-TBI groups on any of the emotional or neurocognitive measures, including PPCS symptoms. Multiple regression analyses revealed that emotional status, such as state anxiety and depression, were the best predictors of PPCS. Furthermore, hierarchical regression analyses revealed a double mediation model, in which suboptimal effort mediated the relationship between neurocognitive performance and PPCS, and emotional status mediated the relationship between suboptimal effort and PPCS. CONCLUSION: These findings underscore the importance of emotional status in the diagnosis of PPCS among children who suffer from PTSD. It is possible that PPCS reflect a more general expression of accident-related emotional distress, rather than being a direct result of the injury. (PsycINFO Database Record PMID- 27548578 TI - Dominant-side onset in Parkinson's disease and better motor performance? PMID- 27548579 TI - Static Compression Induces ECM Remodeling and Integrin alpha2beta1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model. AB - STUDY DESIGN: A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD. OBJECTIVE: The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD. SUMMARY OF BACKGROUND DATA: Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive. METHODS: Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed. RESULTS: In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin alpha2beta1 (upregulated) and alpha10beta1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin alpha1, alpha2, alpha11, and beta1 were upregulated, whereas alpha10 was downregulated. Similar activation of integrin signaling was observed. CONCLUSION: Static compression altered collagen and MMP expression, and promoted beta1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force. LEVEL OF EVIDENCE: N/A. PMID- 27548580 TI - Reoperation Rates After Single-level Lumbar Discectomy. AB - STUDY DESIGN: Retrospective analysis of national insurance billing database. OBJECTIVE: To examine trends in reoperation after single-level lumbar discectomy. SUMMARY OF BACKGROUND DATA: Lumbar discectomy is the most commonly performed procedure for treatment of radiculopathy caused by disc herniation. Randomized clinical trials have demonstrated the advantage of discectomy over nonsurgical treatment options, allowing for a more rapid reduction in symptoms. However, population-level data regarding reoperation after single level discectomy is limited. METHODS: Data were collected using the commercially available PearlDiver software for patients billed with the Current Procedural Terminology code for our index procedure, hemilaminotomy and removal of disc material, between January 2007 and September 2014. The index group was then followed for up to 4 years for recurrent lumbar surgery, including spinal fusion, laminectomy, and additional discectomy. RESULTS: Analysis of data obtained from 13,654 patient records revealed a rate of additional lumbar surgeries after single-level discectomy of 3.95% (539/13654) within 3 months and 12.2% (766/6274) within 4 years of the index procedure. Lumbar spinal fusion was performed on 5.9% (370/6274) of patients within 4 years. Patients who received a re-exploration discectomy within 2 years of the index procedure went on to receive lumbar fusion at a rate of 38.4% (48/125) within the 4 years after the re-exploration discectomy. The average additional cost of lumbar reoperation, as measured by insurance reimbursement, was approximately $11,161 per-patient per year. CONCLUSION: We report an overall 4-year reoperation rate of 12.2% after single-level discectomy. In addition, we report a rate of progression to lumbar fusion following re exploration discectomy of 38.4% within 4 years of reoperation. Further studies are needed regarding the best treatment algorithm in patients with reherniation or iatrogenic instability after lumbar discectomy. This study should enhance the shared decision making process by providing surgeons and patients with valuable data regarding the frequency and nature of reoperations after discectomy. LEVEL OF EVIDENCE: 3. PMID- 27548581 TI - Management of Spine Tuberculosis With Chemotherapy and Percutaneous Pedicle Screws in Adjacent Vertebrae: A Retrospective Study of 34 Cases. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: The objective of this study was to evaluate the efficacy of local chemotherapy combined with percutaneous pedicle screw in adjacent vertebra in the treatment of spine tuberculosis (TB). SUMMARY OF BACKGROUND DATA: Despite the increased treatment concepts and surgical methods, the management of TB, which is increasing in prevalence, remains challenging. Considerable complications existing in the conventional debridement surgery with TB spondylitis requires more attention. METHODS: A retrospective evaluation containing 34 cases of spinal TB (17 males, 17 females; average age 59 years; 14 thoracic TB, 11 thoracolumbar TB, nine lumbar TB) between April 2007 and August 2014 was conducted. All patients were treated with local chemotherapy combined with percutaneous pedicle screw in adjacent vertebrae. The ASIA grade, the Cobb angle, and complications were investigated. RESULTS: All the patients were followed with an average of 18 (range, 12-52) months and were successfully treated without radiculopathy or neurological complications, with 27 excellent and seven fair outcomes at the final follow-up. One case that developed serious abscess in the primary focus underwent anterior focus debridement and bone graft fusion and recovered to the grade of fine at the final following up. As for kyphotic deformity, there was no Cobb angle loss. No other obvious complications were observed in all the patients. CONCLUSION: Local chemotherapy combined with percutaneous pedicle screw in adjacent vertebrae seems an effective method to treat spine TB, with some advantages including smaller trauma, fine neurologic recovery, few complications, and no Cobb angle loss. LEVEL OF EVIDENCE: 3. PMID- 27548582 TI - One-Level Lumbar Degenerative Spondylolisthesis and Posterior Approach: Is Transforaminal Lateral Interbody Fusion Mandatory?: A Randomized Controlled Trial With 2-Year Follow-Up. AB - STUDY DESIGN: A monocentric open-label randomized controlled trial (MRCT). OBJECTIVE: Comparison of clinical and radiological outcomes between isolated instrumented posterior fusion (PLF) and associated instrumented posterior fusion and interbody fusion by transforaminal approach (PLF + TLIF) for patients suffering from one-level lumbar degenerative spondylolisthesis (DS) undergoing surgery. SUMMARY OF BACKGROUND DATA: DS is a common cause of symptomatic lumbar stenosis. PLF has shown better clinical outcome than decompression with noninstrumented posterolateral fusion. TLIF with interbody cage showed better fusion rate than PLF. There is a need for randomized controlled trials to compare PLF with and without TLIF as to clinical and radiological outcomes. METHODS: This is a MRCT comparing PLF and TLIF techniques in surgical treatment of DS. Sixty patients were included in a secured database from 2009 to 2011 and randomized into two groups: 30 PLF with posterior pedicle screws and intertransverse autologuous graft, and 30 TLIF in which an interbody fusion by transforaminal approach was added. Data included clinical (pain and disability), surgical (blood loss and operating time), and radiological (alignment and fusion) parameters at baseline and 2-year follow-up. Comparison was made by Student t test and Chi square test. RESULTS: There was a significant improvement in each group for pain and disability but no difference between the groups. Radiographic assessment showed better posterolateral fusion rate for TLIF without superiority in segmental lordosis improvement. A case of deformity cascade with spino-pelvic mismatch at baseline was noted in PLF. CONCLUSION: Posterior decompression and instrumented fusion is an efficient technique that proved its significant clinical benefit in the surgical treatment of DS. TLIF did not show its superiority neither in clinical nor alignment parameters despite a better fusion rate. These results suggest that TLIF is not mandatory in this specific indication. Sagittal alignment analysis by standing full-body images should be considered in DS care. LEVEL OF EVIDENCE: 2. PMID- 27548584 TI - Complications Associated With Epiphysiodesis for Management of Leg Length Discrepancy. AB - BACKGROUND: Epiphysiodesis is well-established surgical treatment for the management of leg length discrepancy (LLD) in children; however, a variety of complications may occur. This study evaluates the nature, rate, and potential risk factors of complications associated with epiphysiodesis in a large patient population treated in 1 institution. METHODS: We evaluated the medical and radiographic records of 863 children who had lower extremity epiphysiodesis to manage LLD between 1980 and 2011. RESULTS: Sixty patients (7.0%) incurred complications of some type. Twenty-three patients (2.7%) had perioperative complications unrelated to physeal growth; all resolved without surgical treatment. These included 2 patients with transient intraoperative complications (laryngospasm and allergic rash), 7 with transient neurological symptoms (5 cutaneous nerve dysesthesia or numbness and 2 peroneal nerve neuropathies), and 14 with postoperative knee stiffness which resolved with therapy. Thirty-seven patients (4.3%) developed physeal growth-related complications, including 6 patients who developed overcorrection of leg length inequality (3 had contralateral epiphysiodesis to prevent overcorrection, while 3 declined), and 31 patients who developed angular deformity and/or continued growth of the physis. Of these 31 patients, 15 had reexploration of the epiphysiodesis site, 6 underwent corrective osteotomy, while in 10, no treatment was undertaken. Compared with patients who did not develop angular deformity, these 31 patients had significantly greater LLD (5.6 vs. 3.7 cm, respectively, P<0.01), were younger (10.7 vs. 11.7 in girls; 12.4 vs. 13.5 in boys; P<0.01), and were more likely to have a congenital etiology for their LLD (P<0.01). CONCLUSIONS: Epiphysiodesis is a safe and effective procedure for the correction of leg length inequality. The rate of complications in this study was 7.0%, the most prevalent being the development of angular deformity. Congenital etiology, younger age, and larger limb length inequalities were risk factors for the development of angular deformity. Both surgeons and families should be aware of nature and rate of complications associated with epiphysiodesis. LEVEL OF EVIDENCE: Level IV. PMID- 27548583 TI - Tailoring Breast Cancer Screening Intervals by Breast Density and Risk for Women Aged 50 Years or Older: Collaborative Modeling of Screening Outcomes. AB - Background: Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits. Objective: To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer. Design: Collaborative simulation modeling using national incidence, breast density, and screening performance data. Setting: United States. Patients: Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0. Intervention: Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years). Measurements: Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost effectiveness, and ratio of false-positive results to breast cancer deaths averted. Results: Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained. Limitation: Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods. Conclusion: Average-risk women with low breast density undergoing triennial screening and higher-risk women with high breast density receiving annual screening will maintain a similar or better balance of benefits and harms than average-risk women receiving biennial screening. Primary Funding Source: National Cancer Institute. PMID- 27548585 TI - Management of Terminal Osseous Overgrowth of the Humerus With Simple Resection and Osteocartilaginous Grafts. AB - BACKGROUND: Osseous overgrowth is a common complication in children after humeral transcortical amputation. Capping tibial overgrowth with the proximal fibula has been shown to be the most effective treatment. However, best treatment practices are not clear for the humerus. We compared patients treated surgically for humeral osseous overgrowth with simple resection or autologous osteocartilaginous graft to determine if this treatment were as effective in the humerus as it has been in the tibia. METHODS: A retrospective review of humeral amputees from 1987 to 2011 at a pediatric hospital was performed. Patients with 2 years follow-up who underwent surgical treatment for established humeral overgrowth were included. Patients initially managed with simple resection were compared with those managed with autologous osteocartilaginous grafts. Descriptive statistics were calculated for demographic and outcome variables. T tests and chi tests were used to compare differences between groups. RESULTS: Eighteen humeri in 16 patients met inclusion criteria. Mean age at surgery was 8.3 (2.6 to 13.6) years and mean follow-up was 6.3 (1.5 to 10.4) years. Thirteen humeri underwent simple resection, with recurrent overgrowth in 9, and revision surgery in 8 at a mean 2.6 years. Five humeri were primarily managed with autologous osteocartilaginous grafts. Two developed non-overgrowth-related complications at 1 and 42 months. Including revision procedures after simple resection, 10 humeri were managed with autologous osteocartilaginous grafts. Thirty percent (3/10) required revision surgery; however, there were no cases of recurrent overgrowth. chi comparison showed lower rates of complications (P=0.004) and reoperation (P=0.012) with capping as compared with simple resection. CONCLUSIONS: Autologous osteocartilaginous capping of the humerus has a significantly lower rate of complications and reoperation compared with simple resection. However, the capping procedure has the potential for other complications related to difficulty with graft fixation. Surgeons should be aware that the outcomes are not as consistent as when the technique is applied to osseous overgrowth of the tibia and anticipate the possibilities of hardware prominence and difficulty with fixation. LEVEL OF EVIDENCE: Level 3-therapeutic-retrospective comparative. PMID- 27548586 TI - Strategic overview on the best treatment option for intrahepaitc hepatocellular carcinoma recurrence. AB - INTRODUCTION: The long-term survival after hepatectomy for HCC remains unsatisfactory because of the high incidence of recurrence. The cumulative 5-year recurrence rate ranged from 60-100% in previous studies and majority of them remains intrahepatic recurrence. The therapeutic modalities commonly used for primary tumors, including surgical resection, liver transplantation, TACE, local ablative therapy and radiotherapy have been used to treat recurrent tumors in the liver remnant and the outcomes with the heterogeneous therapeutic options are reviewed. It is important to note that the level of evidence for most therapeutic options is limited to cohort investigations with few RCTs and most were limited due to enrollment of various tumor stages and did not compare treatment modalities for specific tumor stages. AREAS COVERED: A literature search for recurrent HCC was performed using Medline and PubMed up to May 2016. Expert commentary: The long term survival results after re-resection for recurrent HCC were favourable and aggressive management of postoperative intrahepatic recurrence remains the most important strategy in prolonging the survival of patients after resection of HCC. PMID- 27548587 TI - Au-HKUST-1 Composite Nanocapsules: Synthesis with a Coordination Replication Strategy and Catalysis on CO Oxidation. AB - A novel coordination replication of Cu2O redox-template strategy is reported to efficiently fabricate Au-HKUST-1 composite nanocapsule, with a HKUST-1 sandwich shell and an embedded Au nanoparticles layer. The novel synthesis procedure involves forming Au nanoparticles on the surface of Cu2O, transforming partial Cu2O into HKUST-1 shell via coordination replication, and removing the residual Cu2O by acid. The as-prepared Au-HKUST-1 composite nanocapsules displayed high catalytic activity on CO oxidation. PMID- 27548588 TI - Screening of pigmented Bacillus aquimaris SH6 from the intestinal tracts of shrimp to develop a novel feed supplement for shrimp. AB - AIMS: To develop a novel feed supplement for shrimp using pigmented spore-forming bacterial strains isolated from their gastrointestinal tracts. METHODS AND RESULTS: Eight pigmented Bacillus strains were selected from the isolates based on high production of heat-stable spores, typical UV-Vis spectra of produced carotenoids (400-550 nm), and free radical scavenging activity of their extracts. Of the eight strains, the red-orange pigmented Bacillus aquimaris SH6 was selected because it showed the highest abundance in shrimp guts (70% population). Whiteleg shrimp (n = 30 per group) fed with SH6 spores, at >3 * 106 CFU g-1 pellet for 4 weeks had redder colour (score of 21-23 vs 20-22), 2.7-fold higher astaxanthin level (0.69 vs 0.25 MUg g-1 shrimp), 34% higher weight gain (7.18 vs 5.32 g shrimp-1 ), and 85% higher phenoloxidase activity (OD490 = 0.265 vs 0.143) than shrimp in the control group. CONCLUSIONS: The result supports the potential use of B. aquimaris SH6 as a feed supplement for promoting the colourization and weight gain, and for enhancing innate immunity of whiteleg shrimp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that carotenoids produced by B. aquimaris SH6 can be successfully absorbed and converted to astaxanthin in whiteleg shrimp. PMID- 27548589 TI - The energetic and carbon economic origins of leaf thermoregulation. AB - Leaf thermoregulation has been documented in a handful of studies, but the generality and origins of this pattern are unclear. We suggest that leaf thermoregulation is widespread in both space and time, and originates from the optimization of leaf traits to maximize leaf carbon gain across and within variable environments. Here we use global data for leaf temperatures, traits and photosynthesis to evaluate predictions from a novel theory of thermoregulation that synthesizes energy budget and carbon economics theories. Our results reveal that variation in leaf temperatures and physiological performance are tightly linked to leaf traits and carbon economics. The theory, parameterized with global averaged leaf traits and microclimate, predicts a moderate level of leaf thermoregulation across a broad air temperature gradient. These predictions are supported by independent data for diverse taxa spanning a global air temperature range of ~60 degrees C. Moreover, our theory predicts that net carbon assimilation can be maximized by means of a trade-off between leaf thermal stability and photosynthetic stability. This prediction is supported by globally distributed data for leaf thermal and photosynthetic traits. Our results demonstrate that the temperatures of plant tissues, and not just air, are vital to developing more accurate Earth system models. PMID- 27548591 TI - Increased Alignment in Preventive Services Recommendations for Children. PMID- 27548592 TI - Behavioral Disorders in Dementia: Appropriate Nondrug Interventions and Antipsychotic Use. AB - Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy. PMID- 27548593 TI - Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management. AB - Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient's family physician to improve chronic care as well as preventive health services. PMID- 27548594 TI - Failure to Thrive: A Practical Guide. AB - Children with very low weight for age or height and those who do not maintain an appropriate growth pattern may have failure to thrive (FTT), also known as weight faltering. If confirmed by repeated valid measurements, FTT should prompt a search for causes of undernutrition, including neglect, family food insecurity, and underlying medical conditions. Inadequate caloric intake is the most common cause of FTT, but inadequate nutrient absorption or increased metabolism is also possible. Difficulty attaining or maintaining appropriate weight is the first indication of FTT, and sustained undernutrition can impede appropriate height, head circumference, and the development of cognitive skills or immune function in extreme cases. Early identification and management of the issues causing undernutrition are critical. In most cases, an appropriate growth velocity can be established with outpatient management based on proper nutrition and family support. Primary care physicians can effectively treat most children with FTT, and subspecialist consultation or hospitalization is rarely indicated. PMID- 27548595 TI - Joint Pain and Fatigue: It Could Be Anything. PMID- 27548596 TI - Screening for Depression in Adults. PMID- 27548597 TI - Predicting Hospital Readmission. PMID- 27548598 TI - Alirocumab (Praluent) for Treatment of Hyperlipidemia. PMID- 27548599 TI - Foot Deformity at Time of Delivery in a Premature Infant. PMID- 27548604 TI - AAP Updates Recommendations for Routine Preventive Pediatric Health Care. AB - Run by Jan 2017. PMID- 27548605 TI - Screening for Depression in Adults: Recommendation Statement. PMID- 27548606 TI - Behavior Problems in a Family Member with Dementia. PMID- 27548607 TI - Failure to Thrive: What You Should Know. PMID- 27548608 TI - Lupus: What You Should Know. PMID- 27548609 TI - Association Between Drinking and Obesity in Pre- and Postmenopausal Women: Korea National Health and Nutrition Examination Survey 2010-2012. AB - BACKGROUND: Women are more vulnerable to the adverse effects of alcohol than men. The present study aimed to investigate the link between drinking and obesity in pre- and postmenopausal women in Korea. METHODS: We performed a cross-sectional study of 4374 premenopausal and 2927 postmenopausal women using a multistage probability cluster survey sample to produce nationally representative estimates. We assessed the subjects' alcohol drinking tendencies rates according to their drinking levels as well as Alcohol Use Disorders Identification Test (AUDIT); obesity was identified based on body mass index (BMI) >=25 kg/m2, waist circumference (WC) >=80 cm, and waist-to-height ratio (WHtR) >=50%. We performed t-tests and chi-square tests to assess the association between drinking and obesity. RESULTS: In premenopausal subjects, obesity indices increased significantly as alcohol consumption rose. Significant correlations between drinking level and obesity factors were found in premenopausal women after adjusting for age (odds ratios [ORs] for BMI, WC, and WHtR were 1.58 [1.08-2.31], 1.94 [1.11-3.00], and 1.80 [1.24-2.61], respectively). Furthermore, an AUDIT score of 20 or higher indicated a significantly higher likelihood of obesity (ORs for BMI, WC, and WHtR were 2.02 [1.18-3.46], 2.75 [1.70-4.87], and 2.86 [1.78 4.59], respectively). There was a significant correlation between AUDIT scores and obesity factors after adjusting for age, energy intake, fat intake, exercise, smoking, education, and income in premenopausal women (ORs for BMI and WHtR were 1.71 [0.85-3.47] and 1.73 [0.97-3.06], respectively). CONCLUSION: Our results suggest that alcohol is associated with a risk factor for obesity in premenopausal women. PMID- 27548610 TI - Scaffolds and Cell-Based Tissue Engineering for Blood Vessel Therapy. AB - The increasing morbidity of cardiovascular diseases in modern society has made it crucial to develop a small-caliber blood vessel. In the absence of appropriate autologous vascular grafts, an alternative prosthesis must be constructed for cardiovascular disease patients. The aim of this article is to describe the advances in making cell-seeded cardiovascular prostheses. It also discusses the combinations of types of scaffolds and cells, especially autologous stem cells, which are suitable for application in tissue-engineered vessels with the favorable properties of mechanical strength, antithrombogenicity, biocompliance, anti-inflammation, fatigue resistance and long-term durability. This article highlights the advancements in cellular tissue-engineered vessels in recent years. PMID- 27548611 TI - Effective one-pot multienzyme (OPME) synthesis of monotreme milk oligosaccharides and other sialosides containing 4-O-acetyl sialic acid. AB - A facile one-pot two-enzyme chemoenzymatic approach has been established for the gram (Neu4,5Ac2alpha3Lac, 1.33 g) and preparative scale (Neu4,5Ac2alpha3LNnT) synthesis of monotreme milk oligosaccharides. Other O-acetyl-5-N-acetylneuraminic acid (Neu4,5Ac2)- or 4-O-acetyl-5-N-glycolylneuraminic acid (Neu4Ac5Gc) containing alpha2-3-sialosides have also been synthesized in the preparative scale. Used as an effective probe, Neu4,5Ac2alpha3GalbetapNP was found to be a suitable substrate by human influenza A viruses but not bacterial sialidases. PMID- 27548612 TI - Low Exercise Capacity Increases the Risk of Low Cognitive Function in Healthy Young Men Born Preterm: A Population-Based Cohort Study. AB - BACKGROUND: Preterm birth is a risk factor for decreased exercise capacity and impaired cognitive functions in later life. The objective of this study was to disentangle the associations between preterm birth, physical fitness and cognitive performance in young adulthood. METHODS: This population-based cohort study included 218,802 young men born in Sweden 1973-1983. Data on birth characteristics was obtained from the Medical Birth Register and linked to exercise capacity assessed by ergometer cycling and cognitive tests performed at conscription for military service in 1993-2001. Cognitive performance was assessed using stanine (STAndard NINE) scores. The results were adjusted for socioeconomic factors. RESULTS: Exercise capacity was positively associated with cognitive performance across all gestational ages. The sub-group of men who were born extremely preterm (gestational age <28 weeks) and had low exercise capacity exhibited the lowest odds ratio (OR = 0.26, 95%CI:0.09-0.82) of having a cognitive function above the mean stanine score (2.9) for men born at term with normal birth weight. Men born extremely preterm with a high exercise capacity had similar or even higher ORs for cognitive function (OR = 0.59; 95% CI:0.35-0.99) than men born at term with low Wmax (OR = 0.57; 95% CI:0.55-0.59). CONCLUSIONS: Physical fitness is associated with higher cognitive function at all gestational ages, also in young men born extremely preterm. Targeting early physical exercise may be a possible intervention to enhance cognitive performance and educational achievements in populations at risk, such as childhood and adult survivors of preterm birth. PMID- 27548613 TI - Crystal Structure of C-Terminal Coiled-Coil Domain of SYCP1 Reveals Non-Canonical Anti-Parallel Dimeric Structure of Transverse Filament at the Synaptonemal Complex. AB - The synaptonemal complex protein 1 (SYCP1) is the main structural element of transverse filaments (TFs) of the synaptonemal complex (SC), which is a meiosis specific complex structure formed at the synapse of homologue chromosomes to hold them together. The N-terminal domain of SYCP1 is known to be located within the central elements (CEs), whereas the C-terminal domain is located toward lateral elements (LEs). SYCP1 is a well-known meiosis marker that is also known to be a prognostic marker in the early stage of several cancers including breast, gliomas, and ovarian cancers. The structure of SC, especially the TF structure formed mainly by SYCP1, remains unclear without any structural information. To elucidate a molecular basis of SC formation and function, we first solved the crystal structure of C-terminal coiled-coil domain of SYCP1. The coiled-coil domain of SYCP1 forms asymmetric, anti-parallel dimers in solution. PMID- 27548614 TI - Before-School Running/Walking Club and Student Physical Activity Levels: An Efficacy Study. AB - PURPOSE: Before-school programs, one of the least studied student-related comprehensive school physical activity program (CSPAP) components, may be a promising strategy to help youth meet the physical activity (PA) guidelines. This study's purpose was to examine: (a) how much PA children accrued during a before school running/walking club and during the school day, (b) whether children compensated for the PA accumulated in the before-school program by decreasing their school-day PA, and (c) potential sex and body mass index (BMI) differences. METHOD: An alternating treatments design with a baseline phase was first conducted at a private school (School A) and was subsequently replicated at a public school (School B). Participants (N = 88) were 3rd- and 4th-grade children. The before-school program involved a running/walking club that met twice per week (School A: 20 min; School B: 15 min). PA was measured using the NL-1000 pedometer. Data analysis included multilevel modeling and visual analysis. RESULTS: Children accumulated substantial amounts of PA in the before-school programs (School A: 1,731 steps, 10:02 moderate-to-vigorous PA minutes or 50% of program duration; School B: 1,502 steps, 8:30 moderate-to-vigorous PA minutes or 57% of program duration). Additionally, children did not compensate by decreasing their school-day PA on days they attended the before-school program. Sex differences were found in before-school program PA only for School B and in school-day PA for both schools. No BMI differences were found. CONCLUSIONS: Before-school programs, as part of CSPAPs, can help children increase their PA without resulting in decreased school-day PA and without taking time away from academics. PMID- 27548615 TI - Post-traumatic Stress Disorder, Bronchodilator Response, and Incident Asthma in World Trade Center Rescue and Recovery Workers. AB - RATIONALE: Post-traumatic stress disorder (PTSD) has been associated with asthma in cross-sectional studies. Whether PTSD leads to clinically significant bronchodilator response (BDR) or new-onset asthma is unknown. OBJECTIVES: We sought to determine the relationship between probable PTSD and both BDR and incident asthma in a high-risk cohort of World Trade Center workers in New York (NY). METHODS: This study was conducted on data from a high-risk cohort of 11,481 World Trade Center workers in New York, including 6,133 never smokers without a previous diagnosis of asthma. Of the 6,133 never smokers without asthma, 3,757 (61.3%) completed a follow-up visit several years later (mean = 4.95 yr, interquartile range = 3.74-5.90 yr). At the baseline visit, probable PTSD was defined as a score 44 points or greater in the PTSD Checklist questionnaire, and BDR was defined as both a change of 12% or greater and an increment of 200 ml or greater in FEV1 after bronchodilator administration. Incident asthma was defined as a self-report of new physician-diagnosed asthma after the baseline visit. Multivariable logistic regression was used for the analysis of probable PTSD and baseline BDR or incident asthma. Measurements and Main and Results: At baseline, probable PTSD was associated with BDR among all participants (adjusted odds ratio = 1.43; 95% confidence interval = 1.19-1.72), with similar results among never smokers without asthma. Among 3,757 never smokers, probable PTSD at baseline was associated with incident asthma, even after adjustment for baseline BDR (odds ratio = 2.41; 95% confidence interval = 1.85-3.13). This association remained significant in a confirmatory analysis after excluding 195 subjects with baseline BDR. CONCLUSIONS: In a cohort of adult workers exposed to a severe traumatic event, probable PTSD is significantly associated with BDR at baseline and predicts incident asthma. PMID- 27548616 TI - Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors. AB - Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123 specific CARs for treatment of CD123+ hematologic malignancies. PMID- 27548617 TI - Method Validation for Extraction of Nucleic Acids from Peripheral Whole Blood. AB - BACKGROUND: This article is the fifth in a series of publications providing formal method validation for biospecimen processing. We report the optimization and validation of methodology to obtain nucleic acids of sufficient quantity and quality from blood. METHODS: DNA was extracted using the Chemagic DNA Blood Kit on an MSM I. Extraction was optimized in terms of blood volume, elution buffer volume, and lysis conditions. The optimal protocol was validated for reproducibility, robustness (delay to buffy coat extraction, blood vs. buffy coat, and use of a magnetic rack), and performance (yield, purity, and concentration). RNA was extracted using a PAXgene Blood miRNA kit with a QiaCube. The protocol was validated for reproducibility, robustness (elution buffer, delay, and temperature before extraction), and performance (yield, purity, integrity, and miRNA content). Two platforms (QiaCube, Biorobot Universal) were further compared. RESULTS: For DNA extraction, a 4 mL blood sample, manual lysis, and 300 MUL elution buffer were found to be reproducible (CV <10% for DNA yield and A260 nm/A280 nm ratio) and robust (buffy coat vs. whole blood; immediate processing of buffy coat after lysis vs. storage for 1 week at 2-8 degrees C; and magnetic rack use). There was no difference between automated and manual lysis. RNA extracted with the PAXgene Blood miRNA kit on a QiaCube gave high yields and optimal reproducibility (low CV for RNA yield and integrity) with BR5 elution buffer (vs. water and TE). PAXgene tubes could be stored for up to 2 weeks at 2-8 degrees C. The Biorobot Universal System gave similar mean RNA yields with Qiacube and slightly lower but acceptable purity. CONCLUSIONS: We validated automated isolation of DNA with a Chemagic DNA Blood Kit on a magnetic bead-based MSM I, and of RNA with a PAXgene Blood miRNA kit on a silica membrane-based QiaCube or Biorobot (for low and high throughput, respectively). PMID- 27548619 TI - Outcome and Safety of Anterograde and Retrograde Single-Balloon Enteroscopy: Clinical Experience at a Tertiary Medical Center in Taiwan. AB - Single-balloon enteroscopy (SBE) is designed for identifying possible small bowel lesions with balloon-assisted enteroscopy that allows deep intubation of the intestine. However, data regarding the outcome and safety of SBE remain limited. We conducted this study to evaluate the outcome and safety of anterograde and retrograde SBE approaches. This retrospective review from a tertiary medical center in Taiwan included endoscopic reports and chart data from 128 patients with 200 anterograde and retrograde procedures from September 2009 to November 2014. In this study, the most common indication for both anterograde and retrograde SBE was obscure gastrointestinal bleeding (64.4% vs. 60.6%). There were no significant differences between anterograde and retrograde approaches in terms of the diagnostic yield (69.3% vs. 52.5%) and intervention rate (23.8% vs. 17.2%). The procedure time was shorter for anterograde SBE than for retrograde SBE (68.1 +/- 23.9 vs. 76.8 +/- 27.7 min, P = 0.018). In addition, among the subgroup of patients with obscure gastrointestinal bleeding, the most common etiologies for those in different age-groups were angiodysplasia (>= 65 years), non-specific ulcers (30-64 years), and Meckel's diverticulum (< 30 years). The major complication rate during the study was 1.5%; the rate of asymptomatic hyperamylasemia was higher for patients who underwent anterograde SBE than for those who underwent retrograde SBE (13.9% vs. 2%, P = 0.005). The outcome and safety of anterograde and retrograde SBE are similar. However, anterograde SBE has a shorter procedural time and a higher rate of asymptomatic hyperamylasemia. PMID- 27548618 TI - Liver Necrosis and Lethal Systemic Inflammation in a Murine Model of Rickettsia typhi Infection: Role of Neutrophils, Macrophages and NK Cells. AB - Rickettsia (R.) typhi is the causative agent of endemic typhus, an emerging febrile disease that is associated with complications such as pneumonia, encephalitis and liver dysfunction. To elucidate how innate immune mechanisms contribute to defense and pathology we here analyzed R. typhi infection of CB17 SCID mice that are congenic to BALB/c mice but lack adaptive immunity. CB17 SCID mice succumbed to R. typhi infection within 21 days and showed high bacterial load in spleen, brain, lung, and liver. Most evident pathological changes in R. typhi-infected CB17 SCID mice were massive liver necrosis and splenomegaly due to the disproportionate accumulation of neutrophils and macrophages (MPhi). Both neutrophils and MPhi infiltrated the liver and harbored R. typhi. Both cell populations expressed iNOS and produced reactive oxygen species (ROS) and, thus, exhibited an inflammatory and bactericidal phenotype. Surprisingly, depletion of neutrophils completely prevented liver necrosis but neither altered bacterial load nor protected CB17 SCID mice from death. Furthermore, the absence of neutrophils had no impact on the overwhelming systemic inflammatory response in these mice. This response was predominantly driven by activated MPhi and NK cells both of which expressed IFNgamma and is considered as the reason of death. Finally, we observed that iNOS expression by MPhi and neutrophils did not correlate with R. typhi uptake in vivo. Moreover, we demonstrate that MPhi hardly respond to R. typhi in vitro. These findings indicate that R. typhi enters MPhi and also neutrophils unrecognized and that activation of these cells is mediated by other mechanisms in the context of tissue damage in vivo. PMID- 27548620 TI - "Whosoever Looketh on a Person to Lust After Them": Religiosity, the Use of Mainstream and Nonmainstream Sexually Explicit Material, and Sexual Satisfaction in Heterosexual Men and Women. AB - While previous research has generally found that religiosity is associated with negative attitudes toward sexually explicit material (SEM) and a lower frequency of SEM use, no studies have examined the relationship between SEM type and religiosity. In addition, it is unknown how the interrelations between religiosity and type and frequency of SEM use influence the relationship between SEM use and sexual satisfaction. Here, associations among a multi-item religiosity scale (consisting of measures of self-reported faith in God, religious services attendance, and the religiosity of the respondent's social network), SEM use, type of preferred SEM, and sexual satisfaction were explored using a large online sample of Croatian adults (N = 2,580). In both men and women, religiosity was associated with less frequent SEM use and more SEM negative attitudes. Guilty feelings following SEM use and SEM-negative attitudes fully mediated the association between religiosity and SEM use among women and partially mediated the relationship for men. Religiosity was also negatively correlated with women's nonmainstream SEM use. For women, religiosity significantly moderated the association between SEM use and sexual satisfaction, as well as the relationship between nonmainstream SEM use and sexual satisfaction. In line with the erotic plasticity theory, the findings suggest that religiosity affects SEM use and related sexual satisfaction more substantially among women than men. PMID- 27548622 TI - Lithium-Ion-Battery Anode Materials with Improved Capacity from a Metal-Organic Framework. AB - We present a porous metal-organic framework (MOF) with remarkable thermal stability that exhibits a discharge capacity of 300 mAh g(-1) as an anode material for a lithium-ion battery. Pyrolysis of the obtained MOF gives an anode material with improved capacity (741 mAh g(-1)) and superior cyclic stability. PMID- 27548621 TI - Tumors Alter Inflammation and Impair Dermal Wound Healing in Female Mice. AB - Tissue repair is an integral component of cancer treatment (e.g., due to surgery, chemotherapy, radiation). Previous work has emphasized the immunosuppressive effects of tumors on adaptive immunity and has shown that surgery incites cancer metastases. However, the extent to which and how tumors may alter the clinically relevant innate immune process of wound healing remains an untapped potential area of improvement for treatment, quality of life, and ultimately, mortality of cancer patients. In this study, 3.5 mm full-thickness dermal excisional wounds were placed on the dorsum of immunocompetent female mice with and without non malignant flank AT-84 murine oral squamous cell carcinomas. Wound closure rate, inflammatory cell number and inflammatory signaling in wounds, and circulating myeloid cell concentrations were compared between tumor-bearing and tumor-free mice. Tumors delayed wound closure, suppressed inflammatory signaling, and altered myeloid cell trafficking in wounds. An in vitro scratch "wounding" assay of adult dermal fibroblasts treated with tumor cell-conditioned media supported the in vivo findings. This study demonstrates that tumors are sufficient to disrupt fundamental and clinically-relevant innate immune functions. The understanding of these underlying mechanisms provides potential for therapeutic interventions capable of improving the treatment of cancer while reducing morbidities and mortality. PMID- 27548623 TI - Cyber Victimization, Psychological Intimate Partner Violence, and Problematic Mental Health Outcomes Among First-Year College Students. AB - Both cyber victimization and psychological intimate partner violence (IPV) have been associated with negative mental health outcomes among adolescents and young adults. The present study examined relations among cyber victimization, psychological IPV, and mental health outcomes (depressive symptoms, antisocial behavior) among first-year college students. Consistent with polyvictimization theory, we hypothesized that cyber victimization and psychological IPV would be related to each other. We also hypothesized that each would uniquely contribute to depressive symptoms and antisocial behavior, after accounting for the other. Participants (N = 342, M age = 18.33 years; 50% male) completed questionnaires during a single lab visit. Results indicated that cyber victimization and psychological IPV were related to each other, and both contributed uniquely to depressive symptoms, but only cyber victimization contributed uniquely to antisocial behavior. Exploratory analyses indicated that experiencing both cyber victimization and psychological IPV was necessary for increased depressive symptoms and antisocial behavior. This study is the first to establish a unique relation between cyber victimization and mental health problems, after accounting for psychological IPV. The findings also suggest a need to consider multiple forms of victimization when considering relations between specific types of victimization and mental health problems. PMID- 27548624 TI - Barriers experienced by patients with multiple sclerosis in seeking care for lower urinary tract symptoms. AB - AIM: The Actionable Bladder Symptom and Screening Tool (ABSST) is used to identify multiple sclerosis (MS) patients in possible need of evaluation for urinary symptoms. The primary objective of this study was to identify barriers experienced by MS patients in seeking evaluation for urinary symptoms. We also assessed the utility of ABSST tool in identifying patients that will follow up with urologic evaluation. METHODS: This was a prospective observational study where 100 patients with MS were enrolled from an MS center. Patients completed demographic information, questions to assess barriers to care, a short form of the ABSST, and incontinence questionnaires. An ABSST score >3 met criteria for referral and evaluation. One year after enrollment, follow up calls assessed whether patients had seen a urinary specialist. RESULTS: The most common barriers to seeking care included "Doctor never referred" (16%) and "Doctor never asked" (13%). Thirty-eight percent (n = 8/21) of men stated "Doctor never referred" compared to 10% (n = 8/79) of women (P = 0.002). Twenty-seven patients had an ABSST Score >=3 and were more interested in seeing a specialist compared to those scoring <3 (88.9%, n = 24/27 vs. 26%, n = 19/73; P = <0.001). After 1 year, 70 patients were reached for follow up. A total of 57.9% (n = 11/19) patients who followed up for evaluation screened positive on the ABSST. CONCLUSIONS: The ABSST is a valuable tool to identify MS patients with urinary symptoms who will likely follow up for genitourinary evaluation. However, other barriers beyond awareness exist and prevent patients from being evaluated. PMID- 27548625 TI - Update on the effects of treatment with recombinant tissue-type plasminogen activator (rt-PA) in acute ischemic stroke. AB - INTRODUCTION: Acute ischemic stroke (AIS) represents a major cause of death and disability all over the world. The recommended therapy aims at dissolving the clot to re-establish quickly the blood flow to the brain and reduce neuronal injury. Intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) is clinically used with this goal. AREAS COVERED: A description of beneficial and detrimental effects of rt-PA treatment is addressed. An overview of new therapies against AIS, such as new thrombolytics, sonolysis and sonothrombolysis, endovascular procedures, and association therapies is provided. Updates on the pathophysiological process leading to intracranial hemorrhage (ICH) is also discussed. EXPERT OPINION: rt-PA treatment in AIS patients is beneficial to recovery outcomes. To weaken risks and improve benefits, it might be relevant to consider: i) a definitive identification of risk factors for symptomatic ICH; ii). a better organization of the health care system to reduce time-to-treatment and enhance discharge management. The pharmacological improvement of new thrombolytic drugs (such as tenecteplase and desmoteplase) targeting harmful and maximally exploiting beneficial effects might further reduce mortality and disability in AIS. PMID- 27548626 TI - Accelerated Amidization of Branched Poly(ethylenimine)/Poly(acrylic acid) Multilayer Films by Microwave Heating. AB - Chemical cross-linking of layer-by-layer assembled films promotes mechanical stability and robustness in a wide variety of environments, which can be a challenge for polyelectrolyte multilayers in saline environments or for multilayers made from weak polyelectrolytes in environments with extreme pHs. Heating branched poly(ethylenimine)/poly(acrylic acid) (BPEI/PAA) multilayers at sufficiently high temperatures drives amidization and dehydration to covalently cross-link the film, but this reaction is rather slow, typically requiring heating for hours for appreciable cross-linking to occur. Here, a more than one order of magnitude increase in the amidization kinetics is realized through microwave heating of BPEI/PAA multilayers on indium tin oxide (ITO)/glass substrates. The cross-linking reaction is tracked using infrared spectroscopic ellipsometry to monitor the development of the cross-linking products. For thick films (~1500 nm), gradients in cross-link density can be readily identified by infrared ellipsometry. Such gradients in cross-link density are driven by the temperature gradient developed by the localized heating of ITO by microwaves. This significant acceleration of reactions using microwaves to generate a well defined cross-link network as well as being a simple method for developing graded materials should open new applications for these polymer films and coatings. PMID- 27548627 TI - Fabrication of Novel Bioactive Cellulose-Based Films Derived from Caffeic Acid Phenethyl Ester-Loaded Nanoparticles via a Rapid Expansion Process: RESOLV. AB - Caffeic acid phenethyl ester (CAPE) nanoparticles (NPs) with an average size of ~40 nm obtained from TEM and binomial average sizes of ~90 and ~400 nm obtained from DLS were successfully produced by rapid expansion of subcritical solutions into liquid solvents (RESOLV). The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of CAPE and CAPE-NPs were determined by plate count method against 12 pathogenic and spoilage bacteria and 3 strains of yeast. Total phenolic content (TPC) and antioxidant activities of CAPE-NPs were quantified and subsequently investigated using two assays, including 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP). CAPE-NP-incorporated cellulose-based films were prepared and characterized. MICs and MBCs of CAPE-NPs against most bacteria and Candida albicans were 700 and 1400 MUg/mL, respectively. CAPE-NPs yielded a TPC value of 426.74 MUgGAE/mg and lower antioxidant activities than those of CAPE in ethanol (CAPE-EtOH), whereas BHT yielded lower FRAP than that of CAPE-NPs. The impregnation of CAPE into cellulose-based films was confirmed by FTIR spectra. Moreover, incorporation of only 0.5 wt % CAPE-NPs into the films resulted in an inhibitory effect against microorganisms. Fortunately, incorporation of higher concentration of CAPE-NPs-MC films led to a significantly higher antioxidant activity and vice versa. This indicated that CAPE-NPs significantly enhanced the antimicrobial and antioxidant activities of CAPE. The results show that the environmentally benign supercritical CO2 technique should be generally applicable to NP fabrication of other important bioactive ingredients, especially in liquid form. In addition, it is suggested that CAPE-NPs can be used to reduce the dosage of CAPE and improve their bioavailability and thus merit further investigation for bioactive packaging film and coating applications. PMID- 27548628 TI - Characteristics of Severe Retinopathy of Prematurity in Infants with Birth Weight above 1500 Grams at a Referral Center in Turkey. AB - PURPOSE: To demonstrate the clinical characteristics and treatment outcomes of severe retinopathy of prematurity (ROP) in preterm infants with birth weight (BW) above 1500 g in Turkey. METHODS: A retrospective review of 5920 ROP records was performed in Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital. The records were obtained from ROP treatment center of the same institute between 2011 and 2016. The data comprised the demographic and clinical characteristics including, gestational age, BW, systemic risk factors, zone and stage of ROP, ROP type, treatment modality, treatment outcomes and inborn/outborn status of the babies. RESULTS: A total of 36 infants (71 eyes) with severe ROP and BW> 1500 g were retrieved. There were 30 infants (83.3%) with type 1 ROP and 6 infants (16.7%) with aggressive posterior ROP (APROP). 3 infants (8.3%) were born at our hospital whereas 33 (91.7%) were referred from outer private neonatal intensive care unit (NICU) centers. Zone I APROP was detected during the initial screening. 21 infants (58.3%) underwent laser treatment while 15 (41.7%) received intravitreal bevacizumab (IVB) injections. No unfavorable structural outcome was observed following either treatment modality. CONCLUSION: Severe ROP may occur in heavier preterm infants. Laser treatment and IVB injections were useful in selected cases. Presence of APROP at first examination suggests an earlier screening in heavier babies. Standardization of private NICU centers as well as establishing a national ROP protocol is necessary in Turkey. PMID- 27548629 TI - Spinning Liquid Marble and Its Dual Applications as Microcentrifuge and Miniature Localized Viscometer. AB - Liquid marble offers an attractive droplet manipulation approach by isolating microdroplet in a nonstick encapsulating shell formed via the spontaneous coating of hydrophobic particles onto the liquid surface. While liquid marble prepared using magnetic nanoparticles enables precise spatiotemporal actuation of microdroplets, these manipulations are generally limited to simple and linear spatial maneuver of microdroplets. Herein, we demonstrate the unique and three dimensional spinning of microliter-sized liquid marble (LM) and its subsequent dual applications as (1) the world's smallest centrifuge and (2) a miniature and localized viscometer. Our LM is responsive to an applied rotating magnetic field, with its spinning speed programmable between 0 and 1300 rpm. This spinning generates an unprecedented centrifugal force of >2g in a LM of ~1 mm radius. Such centrifugal force facilitates an outward and radial hydrodynamic flow in the enclosed microdroplet, enabling LM to serve as a microcentrifuge for the sedimentation of nanoparticles with >85% separation efficiency. Furthermore, we apply spinning LM as an ultrasensitive spin-to-viscosity transducer to quantify the viscosity of the external suspended liquid in the relative viscosity (eta/etawater) range of 1-70 using <=1 mL liquid sample. Collectively, the ensemble of benefits offered by spinning LM creates enormous opportunities in the development of multifunctional micromagneto-mechanical devices as promising surface-sensitive microsensor, miniature centrifugal pump, and even microreactor with directed heat and mass transfer mechanism. PMID- 27548630 TI - Proper Use of Inflammatory Bowel Disease Drugs during Pregnancy. AB - Crohn's disease and ulcerative colitis, referred to as inflammatory bowel disease (IBD), are chronic, relapsing conditions. Patients are often diagnosed at a reproductive age, and therefore questions about fertility and reproductions often arise. Preconceptional counseling is the most important aspect in the management of IBD patients with a pregnancy wish. Patients should be counseled on the influence of IBD and IBD drugs on pregnancy. Most drugs are not related to adverse outcome while used during pregnancy. Active disease is related to adverse outcomes; therefore, it is of utmost importance to strive for remission before conception and during pregnancy. PMID- 27548631 TI - The Polarization of M2b Monocytes in Cultures of Burn Patient Peripheral CD14+ Cells Treated with a Selected Human CCL1 Antisense Oligodeoxynucleotide. AB - M2b macrophages (Mphi) play a major role in the increased susceptibility of subacutely burned patients, to sepsis stemming from enterococcal translocation. Certain opportunistic infections in severely burned mice have been controlled by murine CCL1 antisense oligodeoxynucleotide (ODN), a specific polarizer of mouse M2bMphi. In the present study, we have screened CCL1 antisense ODN, which is active against human M2bMphi. Among the 20 CCL1 antisense ODNs synthesized in our laboratory, HCA-11 was shown to be the most active polarizer for human CCL1+CD163+CD14+ cells. Burn patient CCL1+CD163+CD14+ cells (3 * 105 cells/mL) switched to quiescent CCL1-CD163-CD14+ cells within 48 h in cultures supplemented with 100 MUg/mL of HCA-11. After treatment with a 25 MUg/chimera dose of HCA-11, the bacterial growth was not observed in various organs of patient chimeras (gammaNSG mice inoculated with burn patient WBCs) infected with a lethal dose of Methicillin-resistant Staphylococcus aureus. The host antibacterial defenses against certain opportunistic pathogens should be improved in severely burned patients treated with a human CCL1 antisense ODN, HCA-11. PMID- 27548632 TI - Anal Human Papillomavirus Infection among HIV-Infected Men in Korea. AB - BACKGROUND: Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. METHODS: A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. RESULTS: A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. CONCLUSION: Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age. PMID- 27548633 TI - Nonmuscle Myosin IIA Regulates Platelet Contractile Forces Through Rho Kinase and Myosin Light-Chain Kinase. AB - Platelet contractile forces play a major role in clot retraction and help to hold hemostatic clots against the vessel wall. Platelet forces are produced by its cytoskeleton, which is composed of actin and nonmuscle myosin filaments. In this work, we studied the role of Rho kinase, myosin light-chain kinase, and myosin in the generation of contractile forces by using pharmacological inhibitors and arrays of flexible microposts to measure platelet forces. When platelets were seeded onto microposts, they formed aggregates on the tips of the microposts. Forces produced by the platelets in the aggregates were measured by quantifying the deflection of the microposts, which bent in proportion to the force of the platelets. Platelets were treated with small molecule inhibitors of myosin activity: Y-27632 to inhibit the Rho kinase (ROCK), ML-7 to inhibit myosin light chain kinase (MLCK), and blebbistatin to inhibit myosin ATPase activity. ROCK inhibition reduced platelet forces, demonstrating the importance of the assembly of actin and myosin phosphorylation in generating contractile forces. Similarly, MLCK inhibition caused weaker platelet forces, which verifies that myosin phosphorylation is needed for force generation in platelets. Platelets treated with blebbistatin also had weaker forces, which indicates that myosin's ATPase activity is necessary for platelet forces. Our studies demonstrate that myosin ATPase activity and the regulation of actin-myosin assembly by ROCK and MLCK are needed for the generation of platelet forces. Our findings illustrate and explain the importance of myosin for clot compaction in hemostasis and thrombosis. PMID- 27548634 TI - Concurrent Validity and Feasibility of Short Tests Currently Used to Measure Early Childhood Development in Large Scale Studies. AB - In low- and middle-income countries (LIMCs), measuring early childhood development (ECD) with standard tests in large scale surveys and evaluations of interventions is difficult and expensive. Multi-dimensional screeners and single domain tests ('short tests') are frequently used as alternatives. However, their validity in these circumstances is unknown. We examined the feasibility, reliability, and concurrent validity of three multi-dimensional screeners (Ages and Stages Questionnaires (ASQ-3), Denver Developmental Screening Test (Denver II), Battelle Developmental Inventory screener (BDI-2)) and two single-domain tests (MacArthur-Bates Short-Forms (SFI and SFII), WHO Motor Milestones (WHO Motor)) in 1,311 children 6-42 months in Bogota, Colombia. The scores were compared with those on the Bayley Scales of Infant and Toddler Development (Bayley-III), taken as the 'gold standard'. The Bayley-III was given at a center by psychologists; whereas the short tests were administered in the home by interviewers, as in a survey setting. Findings indicated good internal validity of all short tests except the ASQ-3. The BDI-2 took long to administer and was expensive, while the single-domain tests were quickest and cheapest and the Denver-II and ASQ-3 were intermediate. Concurrent validity of the multi dimensional tests' cognitive, language, and fine motor scales with the corresponding Bayley-III scale was low below 19 months. However, it increased with age, becoming moderate-to-high over 30 months. In contrast, gross motor scales' concurrence was high under 19 months and then decreased. Of the single domain tests, the WHO-Motor had high validity with gross motor under 16 months, and the SFI and SFII expressive scales showed moderate correlations with language under 30 months. Overall, the Denver-II was the most feasible and valid multi dimensional test and the ASQ-3 performed poorly under 31 months. By domain, gross motor development had the highest concurrence below 19 months, and language above. Predictive validity investigation is needed to further guide the choice of instruments for large scale studies. PMID- 27548635 TI - Mechanistic Investigations on the Photorearrangement Reactions of M(CO)4(CS) (M = Group 6 Metal). AB - The mechanisms for the photoisomerization reactions are studied theoretically at the M06-2X/Def2-TZVPD level of theory, using the five-coordinated M(CO)4(CS) (M = Cr, Mo, and W) complexes as model systems. This study provides the first theoretical evidence for the mechanisms of these photorearrangements of the five coordinated metal complexes. That is, the photoisomerization process is primary the axial to basal movement of CS. The model study demonstrates that the preferred reaction route for the photorearrangement reactions is as follows: reactant -> Franck-Condon region -> minimum (triplet) -> transition state (triplet) -> triplet/singlet intersystem crossing -> photoproduct. The theoretical results also show that the energy differences between the crucial points are quite small, which demonstrates that the CS group rotates easily to form the different conformations when the M(CO)4(CS) molecules have been photoirradiated. These photochemical mechanisms are consistent with the available experimental observations. PMID- 27548636 TI - Endodermal Cyst of the Third Nerve in a Child. AB - Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management. PMID- 27548637 TI - Therapeutic compliance with rivaroxaban in preventing stroke in patients with non valvular atrial fibrillation: CUMRIVAFA study. AB - OBJECTIVE: To assess compliance with treatment with rivaroxaban in patients with non-valvular atrial fibrillation. METHODS: Prospective, longitudinal, multicenter study, developed in 160 Spanish primary or specialized care centers. We included 412 patients treated with rivaroxaban, prescribed for stroke prevention. Three visits were conducted: baseline, 6 and 12 months. Compliance was measured by using electronic monitors (MEMSs) that use a digital record in the form of a microchip in the lid of the drug container that automatically controls its opening and registers the time and date of the opening. We calculated the average compliance percentage (CP), global and daily compliance. We considered compliance to be when CP was 80-100%. RESULTS: Three hundred and seventy patients ended the study (mean age 75.19, SD: 7.5 years). Global compliance was 84.1% (CI = 79.21 88.99%) and 80.3% (CI = 74.98-85.62%) after 6 and 12 months respectively. Daily compliance was 83.5% (CI = 78.53-88.57%) and 80% (CI = 74.65-85.35%) at 6 and 12 months. Significant differences in the CP between 6 and 12 months were observed. Global CP was 90.77% after 6 months and 89.65% at the end of the study. Daily CP was 90.14% and 87.66% at 6 and 12 months. There were significant CP differences between 6 and 12 months. Non-compliance was associated with a higher number of concomitant diseases, number of drugs taken and weight. CONCLUSIONS: The percentage of compliance with rivaroxaban was high. A profile of variables that need to be modified in current medical practice, associated with non-compliance, was detected. PMID- 27548638 TI - Methadone maintenance dose/weight ratio, long QTc, and EKG screening. AB - BACKGROUND AND OBJECTIVES: Electrocardiogram (EKG) monitoring during methadone maintenance treatment (MMT) has been recommended to prevent potentially fatal prolonged computed QT intervals (QTc). However, risk indicators for obtaining EKGs do not exist. This study assessed 23 variables that might help identify prolonged QTc during MMT. METHODS: EKGs concurrent with methadone serum levels were obtained from 69 veterans during a 5-year study, encompassing 302.8 person years. Two cardiologists hand-measured QT intervals, selecting each patient's longest QTc. QTc categories included: normal duration <440 ms; borderline duration of 440-469 ms; and abnormal duration >=470 ms. QTc's were compared with seven methadone parameters and 16 bio-psycho-social variables using two QTc cut offs (440 and 470 ms). RESULTS: Among the 69 patients, 19 had normal QTc's, 28 had borderline QTc's, and 22 had abnormal QTc's. Methadone dose/weight was moderately correlated with QTc, and independently associated with longer QTc at both 440 and 470 cut-offs. DISCUSSION AND CONCLUSION: Dose/weight >=.49 is useful for screening EKGs for QTc's >=440 cut-off. Dose/weight >=.65 produces high-yield abnormal QTc's >=470 cut-off. SCIENTIFIC SIGNIFICANCE: Methadone dose/weight provides moderately reliable thresholds for making routine screening decisions and urgent clinical decisions to obtain an EKG for prolonged QTc. (Am J Addict 2016;25:499-507). PMID- 27548639 TI - Silicon Nanoparticles with Surface Nitrogen: 90% Quantum Yield with Narrow Luminescence Bandwidth and the Ligand Structure Based Energy Law. AB - Silicon nanoparticles (NPs) have been widely accepted as an alternative material for typical quantum dots and commercial organic dyes in light-emitting and bioimaging applications owing to silicon's intrinsic merits of least toxicity, low cost, and high abundance. However, to date, how to improve Si nanoparticle photoluminescence (PL) performance (such as ultrahigh quantum yield, sharp emission peak, high stability) is still a major issue. Herein, we report surface nitrogen-capped Si NPs with PL quantum yield up to 90% and narrow PL bandwidth (full width at half-maximum (fwhm) ~ 40 nm), which can compete with commercial dyes and typical quantum dots. Comprehensive studies have been conducted to unveil the influence of particle size, structure, and amount of surface ligand on the PL of Si NPs. Especially, a general ligand-structure-based PL energy law for surface nitrogen-capped Si NPs is identified in both experimental and theoretical analyses, and the underlying PL mechanisms are further discussed. PMID- 27548641 TI - Lack of evidence of rotavirus-dependent molecular mimicry as a trigger of coeliac disease. AB - New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human-transglutaminase protein and the dodecapeptide (260-271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti-pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy-proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no-CD children and 107 blood donors. Using enzyme-linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A IgG antibodies against the synthetic peptides pVP7, the human transglutaminase derived peptide (476-487 aa) which shows a homology with VP7 protein and a control peptide. The triple-layered RV particles (TLPs) containing the VP7 protein and the double-layered RV-particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV-TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0.6, P = 0.1). Biopsy-proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non-specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD. PMID- 27548642 TI - Clickable Janus Particles. AB - Janus particles are colloidal analogues of molecular amphiphiles that can self assemble to form diverse suprastructures, exhibit motility under appropriate catalytic reactions, and strongly adsorb to fluid-fluid interfaces to stabilize multiphasic fluid mixtures. The chemistry of Janus particles is the fundamental parameter that controls their behavior and utility as colloid surfactants in bulk solution and at fluid interfaces. To enable their widespread utilization, scalable methods that allow for the synthesis of Janus particles with diverse chemical compositions and shapes are highly desirable. Here, we develop clickable Janus particles that can be modified through thiol-yne click reactions with commercially available thiols. Janus particles are modified to be amphiphilic by introducing either carboxyl, hydroxyl, or amine moieties. We also demonstrate that regulating the extent of the modification can be used to control the particle morphology, and thus the type of emulsion stabilized, as well as to fabricate composite Janus particles through sequential click reactions. Modifying Janus particles through thiol-yne click chemistry provides a fast-reacting, scalable synthesis method for the fabrication of diverse Janus particles. PMID- 27548643 TI - Ebola vaccines - Where are we? AB - The 2014-16 Ebola outbreak in West Africa has by far been the largest and most devastating Ebola outbreak so far. At the start of the epidemic only 2 Ebola DNA vaccine candidates had been tested in clinical trials and the correlate of protection in humans was unknown. International stakeholders coordinated by the World Health Organization agreed to fast-track the development of 2 Ebola vaccine candidates, based on adenovirus and vesicular stomatitis virus (VSV) vectors. Phase I and II clinical trials were initiated in the autumn of 2014 and found both vaccines to be acceptable for proceeding to phase III trials. Despite the epidemic waning in the spring of 2015, by July 2015 preliminary results from a phase III trial in Guinea proved the Ebola VSV vaccine to be effective. PMID- 27548644 TI - TRAJECTORIES OF CHANGE IN ATTACHMENT AND BIOBEHAVIORAL CATCH-UP AMONG HIGH-RISK MOTHERS: A RANDOMIZED CLINICAL TRIAL. AB - Using an intensive short-term longitudinal design, this study first examined whether there were significant differences in maternal sensitivity and intrusiveness after completion of Attachment and Biobehavioral Catch-up (ABC; Dozier & the Infant-Caregiver Project Lab, 2013) when compared to a control condition. The second aim was to explore the rate and shape of change in parenting behaviors. Participants were 24 mothers and their biological children, who were randomly assigned to ABC (n = 13) or a control condition (n = 11). A structured play assessment with each mother and her child was video-recorded prior to randomization into the study, before each intervention session, and at a follow-up visit. A total of 270 videos were coded for sensitivity and intrusiveness. Hierarchical linear growth models were used to estimate the total change in parenting qualities across the 10 intervention sessions when comparing ABC to a control condition. Piecewise hierarchical linear growth models were used to investigate patterns of change across the intervention for mothers within ABC. Mothers in the ABC condition showed greater increases in sensitivity and decreases in intrusiveness than mothers in the control condition. There was evidence for nonlinear patterns of change in sensitivity and intrusiveness among mothers in ABC. These results support the effectiveness of ABC in changing sensitivity quickly. PMID- 27548645 TI - A Bayesian hierarchical model for prediction of latent health states from multiple data sources with application to active surveillance of prostate cancer. AB - In this article, we present a Bayesian hierarchical model for predicting a latent health state from longitudinal clinical measurements. Model development is motivated by the need to integrate multiple sources of data to improve clinical decisions about whether to remove or irradiate a patient's prostate cancer. Existing modeling approaches are extended to accommodate measurement error in cancer state determinations based on biopsied tissue, clinical measurements possibly not missing at random, and informative partial observation of the true state. The proposed model enables estimation of whether an individual's underlying prostate cancer is aggressive, requiring surgery and/or radiation, or indolent, permitting continued surveillance. These individualized predictions can then be communicated to clinicians and patients to inform decision-making. We demonstrate the model with data from a cohort of low-risk prostate cancer patients at Johns Hopkins University and assess predictive accuracy among a subset for whom true cancer state is observed. Simulation studies confirm model performance and explore the impact of adjusting for informative missingness on true state predictions. R code is provided in an online supplement and at http://github.com/rycoley/prediction-prostate-surveillance. PMID- 27548646 TI - Long-Term Outcomes in Patients with Very-Early Onset Autosomal Dominant Polycystic Kidney Disease. AB - BACKGROUND: Long-term clinical outcomes in children with very-early onset (VEO; diagnosis in utero or within the first 18 months of life) autosomal dominant polycystic kidney disease (ADPKD) are currently not well understood. We conducted a longitudinal retrospective cohort study to assess the association between VEO status and adverse clinical outcomes. METHODS: Seventy patients with VEO-ADPKD matched (by year of birth, sex and race/ethnicity) to 70 patients with non-VEO ADPKD who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was VEO status, and outcomes were progression to end-stage renal disease (ESRD), development of hypertension, progression to estimated glomerular filtration rate (eGFR <90 ml/min/1.73 m2), glomerular hyperfiltration (eGFR >=140 ml/min/1.73 m2) and height-adjusted total kidney volume (htTKV) measured by MRI >=600 ml/m. RESULTS: Median follow-up was until 16.0 years of age. There were only 4 ESRD events during the follow-up period, all in the VEO group (p < 0.05). VEO patients were more likely to develop hypertension (hazard ratio, HR 3.15, 95% CI 1.86-5.34; p < 0.0001) and to progress to eGFR <90 ml/min/1.73 m2 (HR 1.97, 95% CI 1.01-3.84; p < 0.05) than non-VEO patients. There was no difference between groups in the development of glomerular hyperfiltration (HR 0.89, 95% CI 0.56-1.42; p = 0.62). There were only 7 patients who progressed to htTKV >=600 ml/m, 4 in the VEO group and 3 in the non-VEO group (p < 0.01). CONCLUSIONS: Several clinical outcomes are worse in patients with VEO-ADPKD compared to non-VEO ADPKD. Children with VEO ADPKD represent a particularly high-risk group of ADPKD patients. PMID- 27548647 TI - Insect Repellants During Pregnancy in the Era of the Zika Virus. AB - Health care providers must be equipped to provide appropriate advice to reproductive-aged patients for protection against the potentially devastating consequences of prenatal Zika virus exposure. The goal of this commentary is to summarize what is known about the safety and toxicity of N,N-diethyl-meta toluamide (DEET) as a topical insect repellant and the pyrethroid permethrin for treatment of fabric, endorsed in the fight against Zika virus. Reviews assessing the safety and toxicity of DEET conducted by the U.S. Environmental Protection Agency and the Canadian Pest Management Regulatory Agency conclude that DEET has low acute toxicity and does not appear to pose a significant health concern to humans when used as directed. Some experimental animal and limited epidemiologic data suggest that prenatal pyrethroid exposure may adversely affect learning and behavior, but this level of evidence pales in comparison to the known risks of Zika virus to the fetal brain. The available evidence has led to the strong recommendation by the Centers for Disease Control and Prevention for use of these products by pregnant women as personal protection against mosquito bites in the fight against Zika virus infection. This message has been affirmed by our obstetrics and gynecology professional organizations. Because Zika virus is unlikely to be the last disease requiring vector control, those with environmental health expertise must continue to join with infectious disease specialists to communicate the potential vulnerability of our youngest (fetuses, infants, and young children) to vector-borne disease, both to the disease itself and to the strategies employed to mitigate the spread of such disease. PMID- 27548648 TI - Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei. AB - Yakushinamides A (1) and B (2), prolyl amides of polyoxygenated fatty acids, have been isolated from the marine sponge Theonella swinhoei as inhibitors of HDACs and SIRTs. Their planar structures were determined by interpretation of the NMR data of the intact molecules and tandem FABMS data of the methanolysis products. For the assignment of the relative configurations of the three contiguous oxymethine carbons in 1 and 2, Kishi's universal NMR database was applied to the methanolysis products. During the assignments of relative configurations of the isolated 1-hydroxy-3-methyl moiety in 1 and the isolated 1-hydroxy-2-methyl moiety in 2, we found diagnostic NMR features to distinguish each pair of diastereomers. The absolute configurations of 1 and 2 were determined by a combination of the modified Mosher's method and Marfey's method. Although the modified Mosher's method was successfully applied to the methanolysis product of 1, this method gave an ambiguous result at C-20 when applied to the methanolysis product of 2, even after oxidative cleavage of the C-14 and C-15 bond. PMID- 27548649 TI - An orthopedist's guide to shoulder ultrasound: a systematic review of examination protocols. AB - BACKGROUND: The utilization of musculoskeletal ultrasound has expanded within the setting of the orthopedic clinic as a cost-effective, point-of-care diagnostic tool for shoulder pathology. In experienced hands, ultrasound exhibits capabilities equivalent to that of magnetic resonance imaging in the diagnosis of many shoulder diseases including full-thickness and partial-thickness rotator cuff tears. Although similarly effective in identifying additional shoulder disease processes, major obstacles to its widespread use include user dependence and intrinsic limitation to extra-articular diagnosis. OBJECTIVES: The purpose of this review is to present a step-by-step guide of how to perform a comprehensive shoulder examination and to discuss the appropriate use, economic benefit and implementation of ultrasound within the clinic. METHODS: A systematic search (June 2016) of PubMed, Scopus, and EMBASE databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for literature presenting shoulder ultrasound examination protocols. Included studies were peer-reviewed articles or academic society endorsed protocols presenting comprehensive sonographic examinations of the adult shoulder. Papers with limited or single structure examination descriptions, non English language, and publication dates before 1980 were excluded. Final papers meeting criteria were secondarily screened for publication after 2005 to reflect the current state of ultrasound imaging. RESULTS AND CONCLUSIONS: The search yielded 1,725 unique articles with 17 studies meeting final selection criteria. Information from identified studies was summarized to formulate a 4-part shoulder examination protocol, including steps most pertinent to orthopedic in-office diagnoses. In agreement with previous studies, the inexperienced orthopedic surgeon can be quickly trained to expert level proficiency in shoulder ultrasound diagnosis. Using an established protocol, a comprehensive, yet effective shoulder ultrasound examination can be performed within ten minutes. Further, ultrasound provides opportunity to off-set costs through the engagement of revenue generating activity for the orthopedic practice. PMID- 27548650 TI - Oxygen Desaturation Index Estimation through Unconstrained Cardiac Sympathetic Activity Assessment Using Three Ballistocardiographic Systems. AB - BACKGROUND: Nocturnal hypoxemia, characterized by abnormally low oxygen saturation levels in arterial blood during sleep, is a significant feature of various pathological conditions. The oxygen desaturation index, commonly used to evaluate the nocturnal hypoxemia severity, is acquired using nocturnal pulse oximetry that requires the overnight wear of a pulse oximeter probe. OBJECTIVES: This study aimed to suggest a method for the unconstrained estimation of the oxygen desaturation index. METHODS: We hypothesized that the severity of nocturnal hypoxemia would be positively associated with cardiac sympathetic activation during sleep. Unconstrained heart rate variability monitoring was conducted using three different ballistocardiographic systems to assess cardiac sympathetic activity. Overnight polysomnographic and ballistocardiographic recording pairs were collected from the 20 non-nocturnal hypoxemia (oxygen desaturation index <5 events/h) subjects and the 76 nocturnal hypoxemia patients. Among the 96 recording pairs, 48 were used as training data and the remaining 48 as test data. RESULTS: The regression analysis, performed using the low-frequency component of heart rate variability, exhibited a root mean square error of 3.33 events/h between the estimates and the reference values of the oxygen desaturation index. The nocturnal hypoxemia diagnostic performance produced by our method was presented with an average accuracy of 96.5% at oxygen desaturation index cutoffs of >=5, 15, and 30 events/h. CONCLUSIONS: Our method has the potential to serve as a complementary measure against the accidental slip-out of a pulse oximeter probe during nocturnal pulse oximetry. The independent application of our method could facilitate home-based long-term oxygen desaturation index monitoring. PMID- 27548651 TI - Myopathy in scleroderma and in other connective tissue diseases. AB - PURPOSE OF REVIEW: This review discusses the most updated literature of myopathy in scleroderma and other connective tissue diseases. RECENT FINDINGS: In the past year, studies have demonstrated that myopathy in scleroderma is associated with poor outcomes such as disability and mortality. In addition, muscle histopathology in scleroderma continues to reveal that it is a heterogeneous entity, and that necrosis and acute neurogenic atrophy may be a more prevalent histopathologic feature in muscle biopsies than previously reported. In other connective tissue diseases such as SLE, the onset of overlap myositis typically does not occur simultaneously as it does in scleroderma or rheumatoid arthritis. SUMMARY: Myopathy in scleroderma is heterogeneous and given that it is associated with poor outcomes, it is imperative that optimal diagnostic strategies and therapies including a classification criterion be developed. In other connective tissue diseases, such as rheumatoid arthritis and systemic lupus erythematosus, myopathy is even more poorly defined and requires more robust studies to clarify both the clinical features and muscle histopathology in this group. PMID- 27548653 TI - The role of myokines in muscle health and disease. AB - PURPOSE OF REVIEW: This article updates on the concept that muscle-derived cytokines (myokines) play important roles in muscle health and disease. RECENT FINDINGS: Interleukin-6 (IL-6) is released from normal skeletal muscle in response to exercise, mediating both anti-inflammatory responses and metabolic adaptations, actions contradictory to the prevailing view that IL-6 is a proinflammatory cytokine that is inducing and propagating disease. The anti inflammatory effects of IL-6 result from its trans-membrane signalling capability, via membrane-bound receptors, whereas its proinflammatory effects result instead from signalling via the soluble IL-6 receptor and gp130. IL-15 is elevated following exercise, promoting muscle fibre hypertrophy in some circumstances, while inducing fibre apoptosis in others. This functional divergence appears because of variations in expression of IL-15 receptor isoforms. Decorin, a recently described myokine, is also elevated following exercise in normal muscle, and promotes muscle fibre hypertrophy by competitively binding to, and thus inhibiting, myostatin, a negative regulator of muscle protein synthesis. Exercise-induced myostatin downregulation thus promotes muscle fibre growth, prompting recent trials of a biological myostatin inhibitor in inclusion body myositis. SUMMARY: Myokines appear to exert diverse beneficial effects, though their mechanistic roles in myositis and other myopathologies remain poorly understood. PMID- 27548652 TI - Aberrant immune response with consequent vascular and connective tissue remodeling - causal to scleroderma and associated syndromes such as Raynaud phenomenon and other fibrosing syndromes? AB - PURPOSE OF REVIEW: Scleroderma and other autoimmune-induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc) associated pulmonary hypertension, which remains a leading cause of death with only a 50-60% of 2-year survival rate. RECENT FINDINGS: Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During coevolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. SUMMARY: Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases. PMID- 27548654 TI - Creating a pro-active health care system to combat chronic diseases in Sri Lanka: the central role of preventive medicine and healthy lifestyle behaviors. AB - INTRODUCTION: The current burden and future escalating threat of chronic diseases, constitutes the major global public health challenge. In Sri Lanka, cardiovascular diseases account for the majority of annual deaths. Data from Sri Lanka also indicate a high incidence and prevalence of pre-diabetes and diabetes; 1 in 5 adults have elevated blood sugar in Sri Lanka. It is well established that chronic diseases share four primary behavioral risk factors: 1) tobacco use; 2) unhealthy diet; 3) physical inactivity; and 4) harmful use of alcohol. AREAS COVERED: Evidence has convincingly shown that replacing these behavioral risk factors with the converse, healthy lifestyle characteristics, decrease the risk of poor outcomes associated with chronic disease by 60 to 80%. In essence, prevention or reversal of these behavioral risk factors with effective healthy lifestyle programing and interventions is the solution to the current chronic disease crisis. Expert commentary: Healthy lifestyle is medicine with global applicability, including Sri Lanka and the rest of the South Asia region. This policy statement will discuss the chronic disease crisis in Sri Lanka, its current policies and action implemented to promote healthy lifestyles, and further recommendations on preventive medicine and healthy lifestyle initiatives that are needed to move forward. PMID- 27548656 TI - Recently discovered EZH2 and EHMT2 (G9a) inhibitors. AB - Methyltransferase enzymes are promising epigenetic oncotargets. Recent efforts toward the development of inhibitors of two methyltransferases, EZH2 and G9a, as potential anticancer therapies are reviewed with a focus on the structure activity relationships of compounds published from 2012. Benzamide-substituted 2 pyridones are still by far the most popular selective EZH2 inhibitor class but alternative classes are now being reported. There are now three EZH2 inhibitors in clinical development with the first responses in lymphoma patients with tazemetostat. Potent inhibitors of G9a are also published but no examples have yet reached the clinic. Dual blockage of EZH2-G9a is exemplified by one series of compounds. We conclude this review by presenting the three clinical stage compounds with the first clinical response data. PMID- 27548655 TI - Heterogeneity in Suspected Non-Alzheimer Disease Pathophysiology Among Clinically Normal Older Individuals. AB - Importance: A substantial proportion of clinically normal (CN) older individuals are classified as having suspected non-Alzheimer disease pathophysiology (SNAP), defined as biomarker negative for beta-amyloid (Abeta-) but positive for neurodegeneration (ND+). The etiology of SNAP in this population remains unclear. Objective: To determine whether CN individuals with SNAP show evidence of early Alzheimer disease (AD) processes (ie, elevated tau levels and/or increased risk for cognitive decline). Design, Setting, and Participants: This longitudinal observational study performed in an academic medical center included 247 CN participants from the Harvard Aging Brain Study. Participants were classified into preclinical AD stages using measures of Abeta (Pittsburgh Compound B [PIB] labeled positron emission tomography) and ND (hippocampal volume or cortical glucose metabolism from AD-vulnerable regions). Classifications included stages 0 (Abeta-/ND-), 1 (Abeta+/ND-), and 2 (Abeta+/ND+) and SNAP (Abeta-/ND+). Continuous levels of PiB and ND, tau levels in the medial and inferior temporal lobes, and longitudinal cognition were examined. Data collection began in 2010 and is ongoing. Data were analyzed from 2015 to 2016. Main Outcomes and Measures: Evidence of amyloid-independent tau deposition and/or cognitive decline. Results: Of the 247 participants (142 women [57.5%]; 105 men [42.5%]; mean age, 74 [range, 63-90] years), 64 (25.9%) were classified as having SNAP. Compared with the stage 0 group, the SNAP group was not more likely to have subthreshold PiB values (higher values within the Abeta- range), suggesting that misclassification due to the PiB cutoff was not a prominent contributor to this group (mean [SD] distribution volume ratio, 1.08 [0.05] for the SNAP group; 1.09 [0.05] for the stage 1 group). Tau levels in the medial and inferior temporal lobes were indistinguishable between the SNAP and stage 0 groups (entorhinal cortex, beta = 0.005 [SE, 0.036]; parahippocampal gyrus, beta = -0.001 [SE, 0.027]; and inferior temporal lobe, beta = -0.004 [SE, 0.027]; P >= .88) and were lower in the SNAP group compared with the stage 2 group (entorhinal cortex, beta = -0.125 [SE, 0.041]; parahippocampal gyrus, beta = -0.074 [SE, 0.030]; and inferior temporal lobe, beta = -0.083 [SE, 0.031]; P <= .02). The stage 2 group demonstrated greater cognitive decline compared with all other groups (stage 0, beta = -0.239 [SE, 0.042]; stage 1, beta = -0.242 [SE, 0.051]; and SNAP, beta = -0.157 [SE, 0.044]; P <= .001), whereas the SNAP group showed a diminished practice effect over time compared with the stage 0 group (beta = -0.082 [SE, 0.037]; P = .03). Conclusions and Relevance: In this study, clinically normal adults with SNAP did not exhibit evidence of elevated tau levels, which suggests that this biomarker construct does not represent amyloid-independent tauopathy. At the group level, individuals with SNAP did not show cognitive decline but did show a diminished practice effect. SNAP is likely heterogeneous, with a subset of this group at elevated risk for short-term decline. Future refinement of biomarkers will be necessary to subclassify this group and determine the biological correlates of ND markers among Abeta- CN individuals. PMID- 27548657 TI - Effective Chirality Transfer in [3+2] Reaction between Allenyl-Rhodium and Enal: Mechanistic Study Based on DFT Calculations. AB - Theoretical calculation was performed to study the chirality transfer in a newly reported intramolecular [3+2] cycloaddition of enal and alleno rhodium species, generated in situ from an enynol precursor. [3.3.0] bicyclic system which contains two bridgehead quaternary carbons that can be achieved, the chirality of which are controlled by those of the starting material, and the product stereoselectivity is only determined by the alpha-position of the acetylene moiety. Density functional theory calculations predicted that only the cis [3.3.0] bicyclic product could be generated, regardless of either erythro or threo substrate, which was also confirmed by experimental observations. PMID- 27548659 TI - Fluorine and Gold: A Fruitful Partnership. AB - Gold-catalyzed reactions have witnessed an exponential growth in the past decade. When the unique modes of activation exhibited by gold species meet species with either fluorinated building blocks or fluorinating reagents, new opportunities arise for the development of new methodologies in fluoroorganic chemistry. Indeed, gold and fluorine truly formed a very fruitful partnership, and different types of reactivity emerged from their combination. This review gives an overview of such endeavors. The special properties imparted by fluorine to organic molecules have been exploited in gold-catalyzed processes, allowing for the generation of unprecedented fluorinated chemical entities. Thus, the interaction of gold salts with fluorinated building blocks has been revised. In a second section, recent developments in gold-catalyzed nucleophilic fluorinations have been covered. The development of new gold catalysts that stabilize the Au-F bond as well as recent mechanistic studies in the field raised the interest of these types of methodologies for the generation of new C-F bonds. The use of electrophilic fluorine sources enabled new modes of gold catalysis. The incorporation of Selectfluor as an external oxidant constituted a new paradigm in gold chemistry, incorporating the elusive Au(I)/Au(III) redox couple in gold catalyzed transformations. This strategy provided access to both new fluorinated chemical entities and nonfluorinated derivatives by means of coupling reactions. Those topics have been reviewed in the last two sections. PMID- 27548658 TI - Diagnosis and Characters of Non-Specific Low Back Pain in Japan: The Yamaguchi Low Back Pain Study. AB - STUDY DESIGN: Cross sectional data from the Yamaguchi low back pain study conducted in Yamaguchi prefecture, Japan, was used for this analysis. METHODS: A total of 320 patients were recruited from walk-in orthopedic clinics in Yamaguchi Prefecture, Japan. Patients visited the clinics primarily for low back pain (LBP) and sought treatment between April and May 2015. A self-questionnaire was completed by patients, while radiographic testing and neurological and physical examination was performed by the orthopedist in each hospital. The cause and characters of LBP was determined following examination of the data, regional anesthesia and block injection. RESULTS: 'Specific LBP' was diagnosed in 250 (78%) patients and non-diagnosable, 'non-specific LBP' in 70 (22%) patients. The VAS scores of patients were: LBP, 5.8+/-0.18; leg pain, 2.9+/-0.18 and the intensity of leg numbness was 1.9+/-0.16. Item scores for SF-8 were: general health, 46.6+/-0.40; physical function, 43.5+/-0.51; physical limitations, 42.8+/ 0.53; body pain, 42.1+/-0.52; vitality, 48.4+/-0.37; social function, 46.9+/ 0.53; emotional problems, 48.9+/-0.43; mental health, 46.9+/-0.43. CONCLUSIONS: The incidence of non-specific LBP in Japan was lower than previous reports from western countries, presumably because of variation in the diagnosis of LBP between different health care systems. In Japan, 78% of cases were classified as 'specific LBP' by orthopedists. Identification of the definitive cause of LBP should help to improve the quality of LBP treatment. PMID- 27548660 TI - Simultaneous Use of Intravenous Lipid Emulsion and Plasma Exchange Therapies in Multiple Drug Toxicity. AB - OBJECTIVE: The aim of this study was to highlight the use of combined intravenous lipid emulsion (ILE) and plasma exchange (PE) therapies in multidrug toxicity. CLINICAL PRESENTATION AND INTERVENTION: A 45-year-old woman who attempted suicide by ingesting large quantities of amisulpride (28 g), diazepam (250 mg), valsartan (2,240 mg), aripiprazole (45 mg) and paliperidone (21 mg) was taken to the hospital of Adnan Menderes University School of Medicine. Upon arrival, she exhibited signs of cardiotoxicity and severe depression of the central nervous and respiratory systems. She was treated successfully with ILE for 4 h and PE therapy for 36 h, consecutively. She was discharged on the fourth day of hospitalization having fully recovered. CONCLUSION: The patient was successfully treated with the combination of ILE and PE. PMID- 27548661 TI - STIGMA AROUND HIV IN DENTAL CARE: PATIENTS' EXPERIENCES. AB - Tooth decay and other oral diseases can be highly prevalent among people living with HIV/AIDS (PLWHA). Even though dental professionals are trained to provide equal and non-judgemental services to all, intentional or unintentional biases may exist with regard to PLWHA. We conducted qualitative descriptive research using individual interviews to explore the experiences of PLWHA accessing dental care services in Vancouver, Canada. We interviewed 25 PLWHA, aged 23-67 years; 21 were men and 60% reported fair or poor oral health. Thematic analysis showed evidence of both self-stigma and public stigma with the following themes: fear, self-stigma and dental care; overcoming past offences during encounters with dental care professionals; resilience and reconciliation to achieve quality care for all; and current encounters with dental care providers. Stigma attached to PLWHA is detrimental to oral care. The social awareness of dental professionals must be enhanced, so that they can provide the highest quality care to this vulnerable population. PMID- 27548662 TI - COMPLICATIONS OF ORAL AND MAXILLOFACIAL SURGERY UNDER GENERAL ANESTHESIA IN TUBE FED CHILDREN: A RETROSPECTIVE ANALYSIS. AB - PURPOSE: To assess morbidity and mortality associated with oral and maxillofacial surgery procedures requiring general anesthesia among children with aspiration tendency requiring enteral feeding. MATERIAL AND METHODS: A retrospective chart review was conducted of children surgically treated under general anesthesia by the oral and maxillofacial surgery service at the Hospital for Sick Children in Toronto, Canada. Medical and dental records over a 9-year period (January 1, 2000 to January 1, 2010) were reviewed. Data were collected on demographics, primary illness, coexisting medical conditions, procedures performed, medications administered, type of airway management used, duration of general anesthesia, American Society of Anesthesiologists' physical status classification and adverse events. RESULTS: During the period reviewed, 28 children underwent 35 oral and maxillofacial surgery procedures under general anesthesia. The mean patient age was 12 years (range 4-17 years). No deaths occurred. Of the 35 surgeries, 10 (29%) were associated with at least 1adverse event. Adverse events included 1incident of respiratory distress, 2incidents of fever, 5incidents of bleeding, 1incident of seizure and 4incidents of oxygen saturation below 90% for more than 30s. CONCLUSIONS: Children with a history of aspiration tendency that necessitates enteral feeding, who undergo oral and maxillofacial surgery under general anesthesia, are at increased risk of morbidity. Before initiating treatment, the surgeon and parents or guardians of such children should carefully consider these risks compared with the anticipated benefit of surgery. PMID- 27548663 TI - FLUORIDATION EXPOSURE STATUS BASED ON LOCATION OF DATA COLLECTION IN THE CANADIAN HEALTH MEASURES SURVEY: IS IT VALID? AB - BACKGROUND: Statistics Canada's population health surveys may be an important source of up-to-date evidence on fluoridation and population oral health. The objective of this study was to examine the validity of a geographic measure of fluoridation from a national survey (based on site of data collection), by comparing it with estimates of fluoride level from urine samples. METHODS: The data source is the environmental urine subsample (n=2563) from Cycle 2 (2009 2011) of the Canadian Health Measures Survey. Mean comparison and multivariable linear regression were used to examine whether urinary fluoride levels differed between respondents classified as "fluoridated" versus "non-fluoridated" based on data collection site. RESULTS: Respondents who attended data collection sites classified as fluoridated had significantly higher mean urinary fluoride levels than those who attended sites classified as non-fluoridated. This effect was robust to adjustment for covariates and was somewhat stronger among an "exposed" subpopulation (defined based on tap water consumption and residential history) compared with a non-exposed subpopulation. No apparent added value was associated with using a more precise geographic indicator based on home postal code. CONCLUSIONS: Fluoridation status based on data collection site seems crude, but is actually reasonably accurate compared with fluoride level in urine, in the context of a large national Canadian survey of urban and rural residents. Although findings are of limited use for individual-level risk assessment, they may be of interest to dental public health researchers and to those engaged in public health surveillance, because they inform efficient and readily available options for monitoring fluoridation status in populations. PMID- 27548664 TI - CAREER PLANS OF GRADUATES OF A CANADIAN DENTAL SCHOOL: PRELIMINARY REPORT OF A 5 YEAR SURVEY. AB - OBJECTIVE: Comprehensive data on the characteristics and opinions of graduating dental students in Canada are lacking. Specifically, only minimal information is available on graduates' immediate career plans and factors that may influence their decisions regarding these plans. Our aim was to gather such data to allow better understanding of this issue and improve the design of future studies on this topic. METHODS: The Career Development Committee at the school of dentistry, University of Alberta, designed a short survey to be administered to graduating students over 5 years to gain insight into their immediate career plans and opinions on career services at the school. Preliminary results from 2012-2014 are reported here. RESULTS: With a response rate of close to 90% (n = 99/111), the data reveal considerable differences in immediate career plans between the surveyed students and those in other schools in Canada and the United States. Of the students, 89% were planning to work in a general dental practice and only 9% were planning to enroll in advanced education, including general practice residency training. CONCLUSION: More research is needed to better understand the factors affecting career path decisions of students. PMID- 27548665 TI - EVIDENCE OF EPSTEIN-BARR VIRUS ASSOCIATION WITH HEAD AND NECK CANCERS: A REVIEW. AB - Epstein-Barr virus (EBV) is ubiquitous: over 90% of the adult population is infected with this virus. EBV is capable of infecting both B lymphocytes and epithelial cells throughout the body including the head and neck region. Transmission occurs mainly by exchange of saliva. The infection is asymptomatic or mild in children but, in adolescents and young adults, it causes infectious mononucleosis, a self-limiting disease characterized by lethargy, sore throat, fever and lymphadenopathy. Once established, the virus often remains latent and people become lifelong carriers without experiencing disease. However, in some people, the latent virus is capable of causing malignant tumours, such as nasopharyngeal carcinoma and various B- and T-cell lymphomas, at sites including the head, neck and oropharyngeal region. As lymphoma is the second-most common malignant disease of the head, neck and oral region after squamous cell carcinoma, oral health care workers including dentists and specialists have a responsibility to carry out a thorough clinical examination of this anatomical region with a view to identifying and diagnosing lesions that may represent lymphomas. Early detection allows early treatment resulting in better prognosis. The focus of this review is on the morphology, transmission and carcinogenic properties of EBV and clinical and diagnostic aspects of a range of EBV associated malignancies occurring in the head, neck and oral region. As carcinogenic agents, viruses contribute to a significant proportion of the global cancer burden: approximately 15% of all human cancers, worldwide, are attributable to viruses.1,2 Serologic and epidemiologic studies are providing mounting evidence of an etiologic association between viruses and head and neck malignancies.3 To update oral and maxillofacial surgeons and oral medicine specialists and raise awareness of this association, we recently reviewed the evidence of the etiologic role of human papillomavirus in oral disease.4 In this paper, we review the current state of knowledge of the association of Epstein Barr virus (EBV) with malignant diseases in the head and neck region. PMID- 27548666 TI - TREATING EARLY CHILDHOOD CARIES UNDER GENERAL ANESTHESIA: A NATIONAL REVIEW OF CANADIAN DATA. AB - INTRODUCTION: Many Canadian children are affected by early childhood caries (ECC) and require treatment under general anesthesia. The purpose of this study was to determine the burden of day surgery for children with ECC in Canada. METHODS: Day surgery abstracts for children 6 years of age with ECC were extracted from the Canadian Institute for Health Information Discharge Abstract Database and National Ambulatory Care Reporting System for 4 years, 2010/11 to 2013/14. All provinces and territories participated except Quebec. Variables considered included sex, age, proportion of immigrants in the neighbourhood, Aboriginal concentration, material deprivation index and rurality. Rates were calculated for the pooled 4-year cohort. RESULTS: The overall rate of dental surgery to treat ECC was 12.1 per 1000 children 12-59 months of age, accounting for 31.0% of all day surgeries performed on this age group in Canada. Rates of dental surgery for children from neighbourhoods with a high proportion of Aboriginal people were 7.8 times those for children living in areas with a low proportion (84.5 vs. 10.9 per 1000). For children from rural regions of Canada, rates were 3.2 times those of urban dwelling children (31.2 vs. 9.8 per 1000). Children from the least-affluent regions had dental surgery rates 3.7 times higher than those from the most affluent communities (25.7 vs. 6.9 per 1000). Total hospital-associated costs of treating ECC under general anesthesia averaged $21184545 annually. CONCLUSION: Dental surgery for ECC is far too common and occurs more often among children from the least-affluent households, rural regions and communities with a high proportion of Aboriginal people. Dental surgery rates can serve as an important population health indicator. PMID- 27548667 TI - HOW DO I MANAGE A PATIENT WITH LATERAL LUXATION OF A PERMANENT INCISOR? PMID- 27548668 TI - FEASIBILITY OF IMPLEMENTING A COMMUNITY-BASED ORAL HEALTH EDUCATIONAL TOOL FOR NEWCOMERS IN ALBERTA: PERSPECTIVES OF FRONTLINE COMMUNITY LEADERS. PMID- 27548669 TI - ORAL HEALTH STATUS OF IMMIGRANT AND REFUGEE CHILDREN IN NORTH AMERICA: A SCOPING REVIEW. AB - OBJECTIVES: The aim of this scoping review was to assess the oral health status of the children of refugees and immigrants ("newcomers"); the barriers to appropriate oral health care and use of dental services; and clinical and behavioural interventions for this population in North America. METHODS: Explicit inclusion and exclusion criteria were used in searching electronic databases to identify North American studies between 2007 and 2014 that reported oral health status, behaviours and environment of children of newcomers. Additional studies from 1995-2008 were found in a recently published review. Pertinent data from all selected studies were summarized. RESULTS: Overall, 32 relevant North American studies were identified. In general, children of newcomers exhibit poorer oral health compared with their non-newcomer counterparts. This population faces language, cultural and financial barriers that, consequently, limit their access to and use of dental services. Intervention programs, such as educational courses and counseling, targeting newcomer parents or their children are helpful in improving the oral health status of this population. CONCLUSIONS: Children of newcomers are suffering from poor oral health and face several barriers to use of dental care services. The disparity in dental caries between children of newcomers and their counterparts can be reduced by improving their parents' literacy in the official language(s) and educating parents regarding good oral health practices. An appropriate oral health policy remains crucial for marginalized populations in general and newcomer children in particular. PMID- 27548670 TI - PRACTICE PROFILE OF PERIODONTISTS IN CANADA: A NATIONAL SURVEY. AB - OBJECTIVE: To document the profile of periodontists in private practice in Canada in terms of services provided and referral patterns. METHODS: An online survey consisted on 45 questions in 3 categories: demographics, referral patterns and periodontal procedures performed. The sampling frame consisted of all active members of the Canadian Academy of Periodontology (n= 280). Letters and email containing links to the online survey were used to invite participants and to send reminders to non-respondents on days 7, 21 and 49. RESULTS: The response rate was 164/280 (58.6%); 135 respondents completed the entire survey. Of the respondents who noticed changes in referral dynamics in the last 10 years (68.1%), most (61.9%) perceived an overall decrease in the number of referrals, and 74.0% reported that general dentists were referring patients later in the disease progression. The most common referrals (71.6%) were for limited treatment. Most respondents placed dental implants (93.7%) and performed maxillary sinus lifts (81.6%). All performed surgical debridement, esthetic and prerestorative crown lengthening and connective tissue grafts. Only 13.7% provided photodynamic therapy. Fewer years in practice (<20 years), more recent graduation (after 1990) and younger age (<45 years) were correlated with greater use of single-implant placement, sinus lifts and procedures requiring intravenous sedation. Men were more likely than women to use lasers (p=0.020). CONCLUSION: Periodontal specialists perceived a change in referral dynamics over the last 10 years with most reporting both a decrease in number and delayed timing of referrals. Practice patterns have changed, with younger periodontists performing more advanced surgical procedures. These findings may guide periodontal residency programs and create awareness among general dentists of the role of the periodontist and their repertoire of treatment options. PMID- 27548671 TI - WORK PATTERN DIFFERENCES BETWEEN MALE AND FEMALE ORTHODONTISTS IN CANADA. AB - OBJECTIVE: To examine sex-specific differences in the demographics and work patterns of Canadian orthodontists. METHODS: Questionnaires were mailed and emailed to a random sample of 384 orthodontists: 289 men and 95 women. Questions regarding work patterns and personal demographics were created and results were compared by sex. RESULTS: The response rate was 53.9%. The demographics and work patterns for male and female orthodontists were similar for most variables. Women were found to be 6 years younger; have 6 fewer years of work experience; expect to retire earlier; be more often married to a professional in full-time employment; and be more likely to take a leave of absence during their career than their male colleagues. Age significantly affected the number of hours worked per week and number of phase II starts per year; both variables increased with increasing age until approximately 50 years, after which they decreased with age. Having children did not significantly affect any of the analyzed variables. CONCLUSIONS: As the practice of female orthodontists was not found to be substantially different from that of men, it is not possible to speculate whether the increasing number of women specializing in orthodontics will provoke a significant change in the profession. As this is the first survey of its kind in Canada, these results may be used as a reference for future comparisons to determine work patterns and trends in the orthodontic workforce. PMID- 27548672 TI - THE INFLUENCE OF SYSTEMIC MEDICATIONS ON OSSEOINTEGRATION OF DENTAL IMPLANTS. AB - Dental implants are routinely used to treat edentulism. Their success depends on osseointegration, the direct functional and structural interlocking of implant and bone. The osseointegration mechanism is similar to bone remodeling and healing. Thus, chronic use of systemic medications that can interfere with bone turnover and healing may affect osseointegration, resulting in premature implant loss. The aim of this narrative review is to analyze the reported effects of systemic medications on osseointegration. PMID- 27548673 TI - Gut-Liver Interactions: Full of New Excitements. PMID- 27548674 TI - Improved Simulation of Electrodiffusion in the Node of Ranvier by Mesh Adaptation. AB - In neural structures with complex geometries, numerical resolution of the Poisson Nernst-Planck (PNP) equations is necessary to accurately model electrodiffusion. This formalism allows one to describe ionic concentrations and the electric field (even away from the membrane) with arbitrary spatial and temporal resolution which is impossible to achieve with models relying on cable theory. However, solving the PNP equations on complex geometries involves handling intricate numerical difficulties related either to the spatial discretization, temporal discretization or the resolution of the linearized systems, often requiring large computational resources which have limited the use of this approach. In the present paper, we investigate the best ways to use the finite elements method (FEM) to solve the PNP equations on domains with discontinuous properties (such as occur at the membrane-cytoplasm interface). 1) Using a simple 2D geometry to allow comparison with analytical solution, we show that mesh adaptation is a very (if not the most) efficient way to obtain accurate solutions while limiting the computational efforts, 2) We use mesh adaptation in a 3D model of a node of Ranvier to reveal details of the solution which are nearly impossible to resolve with other modelling techniques. For instance, we exhibit a non linear distribution of the electric potential within the membrane due to the non uniform width of the myelin and investigate its impact on the spatial profile of the electric field in the Debye layer. PMID- 27548675 TI - The Gene Encoding Dihydroflavonol 4-Reductase Is a Candidate for the anthocyaninless Locus of Rapid Cycling Brassica rapa (Fast Plants Type). AB - Rapid cycling Brassica rapa, also known as Wisconsin Fast Plants, are a widely used organism in both K-12 and college science education. They are an excellent system for genetics laboratory instruction because it is very easy to conduct genetic crosses with this organism, there are numerous seed stocks with variation in both Mendelian and quantitative traits, they have a short generation time, and there is a wealth of educational materials for instructors using them. Their main deficiency for genetics education is that none of the genetic variation in RCBr has yet been characterized at the molecular level. Here we present the first molecular characterization of a gene responsible for a trait in Fast Plants. The trait under study is purple/nonpurple variation due to the anthocyaninless locus, which is one of the Mendelian traits most frequently used for genetics education with this organism. We present evidence that the DFR gene, which encodes dihyroflavonol 4-reductase, is the candidate gene for the anthocyaninless (ANL) locus in RCBr. DFR shows complete linkage with ANL in genetic crosses with a total of 948 informative chromosomes, and strains with the recessive nonpurple phenotype have a transposon-related insertion in the DFR which is predicted to disrupt gene function. PMID- 27548676 TI - Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days. AB - Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines. PMID- 27548677 TI - Virus-Like Nanoparticle Vaccine Confers Protection against Toxoplasma gondii. AB - The inner membrane complex (IMC) of Toxoplasma gondii as a peripheral membrane system has unique and critical roles in parasite replication, motility and invasion. Disruption of IMC sub-compartment protein produces a severe defect in T. gondii endodyogeny, the form of internal cell budding. In this study, we generated T. gondii virus-like particle particles (VLPs) containing proteins derived from IMC, and investigated their efficacy as a vaccine in mice. VLP vaccination induced Toxoplasma gondii-specific total IgG, IgG1 and IgG2a antibody responses in the sera and IgA antibody responses in the feces. Upon challenge infection with a lethal dose of T. gondii (ME49), all vaccinated mice survived, whereas all naive control mice died. Vaccinated mice showed significantly reduced cyst load and cyst size in the brain. VLP vaccination also induced IgA and IgG antibody responses in feces and intestines, and antibody-secreting plasma cells, mixed Th1/Th2 cytokines and CD4+/CD8+ T cells from spleen. Taken together, these results indicate that non-replicating VLPs containing inner membrane complex of T. gondii represent a promising strategy for the development of a safe and effective vaccine to control the spread of Toxoplasma gondii infection. PMID- 27548678 TI - Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands. AB - BACKGROUND: In response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1 15 years in selected communities in Choiseul and Western Provinces. METHODOLOGY AND PRINCIPAL FINDINGS: We conducted a post-vaccination campaign, household-level survey about knowledge, attitudes, and practices regarding diarrhea and cholera in areas targeted and not targeted for cholera vaccination. Respondents in vaccinated areas were more likely to have received cholera education in the previous 6 months (33% v. 9%; p = 0.04), to know signs and symptoms (64% vs. 22%; p = 0.02) and treatment (96% vs. 50%; p = 0.02) of cholera, and to be aware of cholera vaccine (48% vs. 14%; p = 0.02). There were no differences in water, sanitation, and hygiene practices. CONCLUSIONS: This pre-emptive OCV campaign in a cholera-naive community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities. PMID- 27548679 TI - Gastroprotection with proton-pump inhibitors in high-risk cardiovascular patients: who to target and for how long? PMID- 27548680 TI - Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data. AB - The neurotransmitter dopamine is heavily implicated in intracranial self stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS. PMID- 27548681 TI - Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans. AB - Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported "liking" the MA-paired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies. PMID- 27548682 TI - Environmental Transmission of the Gut Symbiont Burkholderia to Phloem-Feeding Blissus insularis. AB - The plant-phloem-feeding Blissus insularis possesses specialized midgut crypts, which harbor a dense population of the exocellular bacterial symbiont Burkholderia. Most individual B. insularis harbor a single Burkholderia ribotype in their midgut crypts; however, a diverse Burkholderia community exists within a host population. To understand the mechanism underlying the consistent occurrence of various Burkholderia in B. insularis and their specific association, we investigated potential gut symbiont transmission routes. PCR amplification detected a low titer of Burkholderia in adult reproductive tracts; however, fluorescence in situ hybridization assays failed to produce detectable signals in these tracts. Furthermore, no Burkholderia-specific PCR signals were detected in eggs and neonates, suggesting that it is unlikely that B. insularis prenatally transmits gut symbionts via ovarioles. In rearing experiments, most nymphs reared on St. Augustinegrass treated with cultured Burkholderia harbored the cultured Burkholderia strains. Burkholderia was detected in the untreated host grass of B. insularis, and most nymphs reared on untreated grass harbored a Burkholderia ribotype that was closely related to a plant-associated Burkholderia strain. These findings revealed that B. insularis neonates acquired Burkholderia primarily from the environment (i.e., plants and soils), even though the possibility of acquisition via egg surface cannot be excluded. In addition, our study explains how the diverse Burkholderia symbiont community in B. insularis populations can be maintained. PMID- 27548683 TI - Identification of the Asymptomatic Patient With Severe Mitral Regurgitation: Discrepancy Between Research and Clinical Practice. AB - Organic mitral regurgitation (MR) is a common disorder, and because of the increase in population and its aging, the occurrence of MR is steadily increasing. Current guideline recommendations on the management of asymptomatic severe MR are conflicting and based solely on registries or nonrandomized trials in expert heart valve clinics, resulting in a lack of evidence for the best treatment strategy. In this review, we will evaluate the latest evidence on diagnostic approaches and treatment strategies for asymptomatic patients without a clear indication for surgical intervention. Implications for management in daily practice are discussed, including an update on the diagnostic approaches that are currently available for the evaluation of MR. For optimal care, it is important that every severe MR patient, including the unidentified patient, is referred to a specialized heart team and is assessed on an individual basis according to the guideline recommendations, experience of the surgical center, and the patient's characteristics and preferences. Screening and diagnostic approaches need to be performed on the basis of standardized protocols and strict criteria. In addition, specialized valve centers must meet the surgical criteria to guarantee high reparability rates in asymptomatic patients. Awareness among cardiologists and cardiothoracic surgeons, improved guidelines adherence, and a systematic approach, including strict criteria in the management of asymptomatic patients with severe organic MR, will ensure reliable and applicable results in research and daily clinical practice. PMID- 27548684 TI - Hypertension in the Kidney Transplant Recipient: Overview of Pathogenesis, Clinical Assessment, and Treatment. AB - Cardiovascular disease is the leading cause of death in patients with chronic renal disease and the most common cause of death and allograft loss among kidney transplant recipients. Transplant patients often have multiple cardiovascular risk factors antedating transplantation. Among the most prominent is hypertension (HTN), which affects at least 90% of transplant patients. Uncontrolled HTN is an independent risk factor for allograft loss. The etiology of HTN in transplant recipients is complex and multifactorial, including the use of essential immunosuppressive medications. Post-transplant HTN management requires a systematic and individualized approach with nonpharmacologic and pharmacologic therapies. There is no single ideal agent or treatment algorithm. Patients should regularly monitor and record their blood pressure at home. Often, multiple antihypertensive drugs are needed to achieve a goal blood pressure of 120-140/70 90 mm Hg. As transplant recipients commonly must take 8 to 12 different medications daily, adherence must be continually encouraged and monitored. Special attention must be paid to potential drug side effects and drug interactions with immunosuppressive medications. PMID- 27548685 TI - Enhanced External Counterpulsation Therapy: Past, Present, and Future. AB - External counterpulsation therapy was first developed over half a century ago as a resuscitative tool to support the failing heart and was based on hemodynamic principles of the intraaortic balloon pump. Over the course of last few decades, it has evolved into the modern enhanced external counterpulsation (EECP) therapy, which has proven to be a safe, effective, and low-cost noninvasive treatment for patients with debilitating angina and chronic heart failure who are poor candidates for revascularization procedures and have suboptimal results from other therapies. Numerous studies have shown EECP to be efficacious in patients with chronic angina, with its effects lasting for several years after completion of therapy. Besides being safe in patients with coexisting left ventricular dysfunction, there is emerging evidence that EECP therapy may result in improvement in exercise capacity and oxygen consumption in heart failure patients. Several mechanisms have been postulated to explain the therapeutic effects of EECP, including improvement in endothelial function, promotion of angiogenesis and new collaterals, reduction in atherosclerotic burden, improvement in ventricular function, and peripheral training effects analogous to that of exercise. With greater understanding of these complex mechanisms, possible applications of EECP have broadened in recent years, with its use being studied in conditions like hepatorenal syndrome, erectile dysfunction, and restless leg syndrome. This review article offers a historical perspective on the origins of EECP, an overview of our current understanding of its physiological effects, and a glimpse at its future utilization in clinical practice. PMID- 27548686 TI - Reversal Agents for Direct Oral Anticoagulants: Understanding New and Upcoming Options. AB - Direct oral anticoagulants (DOACs), originally developed as an alternative for vitamin K antagonists, are shifting the landscape of antithrombotic therapy. DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban offer enhancements in safety, convenience, and efficacy compared with warfarin. However, as choices for oral anticoagulation therapy have increased, so has the need for effectual antidotes before urgent surgical procedures and for the reversal of serious adverse events caused by DOACs. To date, one antidote has been FDA approved in the United States for the reversal of dabigatran, and two antidotes are undergoing phase 2and 3clinical trials. This review will summarize currently available and developing data for DOAC antidotes: idarucizumab, exanet alfa, and ciraparantag. PMID- 27548687 TI - Patiromer: The First Potassium Binder Approved in Over 50 Years. AB - For over 50 years, there have been limited options for the management of hyperkalemia, especially among patients with chronic kidney disease (CKD), diabetic nephropathy, hypertension, and heart failure, who were receiving concomitant renin-angiotensin-aldosterone system (RAAS) inhibitor therapy. Hyperkalemia is a potential, life-threatening electrolyte abnormality that frequently challenges clinicians from maximizing the mortality benefit and organ protective properties of RAAS inhibitors especially in CKD and heart failure populations. Patiromer is a novel nonabsorbed, cation-exchange polymer that binds and exchanges potassium for calcium, predominantly in the gastrointestinal tract. It has demonstrated potassium-lowering effects in normo- or hyperkalemic patients on concomitant RAAS inhibitors with heart failure, diabetic nephropathy, and CKD, in the PEARL-HF, AMETHYST-DN, and OPAL-HK studies, respectively. Across all studies, it appears to be generally effective and well tolerated, with adverse events predominantly gastrointestinal in nature. Additional investigational studies are needed to explore its use for an extended duration of treatment and in larger patient populations, as well as exploring drug-drug interactions. Overall, patiromer demonstrates a promising role in the chronic management of hyperkalemia that will allow optimization of RAAS inhibitor therapy, thus delaying progression of CKD and improving the mortality benefit in heart failure patients. PMID- 27548688 TI - High-Intensity Interval Training Versus Moderate-Intensity Continuous Training in the Prevention/Management of Cardiovascular Disease. AB - Moderate-intensity continuous training (MICT) has long been considered the most effective exercise treatment modality for the prevention and management of cardiovascular disease (CVD), but more recently high-intensity interval training (HIIT) has been viewed as a potential alternative to MICT in accruing such benefits. HIIT was initially found to induce significant improvements in numerous physiological and health-related indices, to a similar if not superior extent to MICT. Since then, many studies have attempted to explore the potential clinical utility of HIIT, relative to MICT, with respect to treating numerous cardiovascular conditions, such as coronary artery disease, heart failure, stroke, and hypertension. Despite this, however, the efficacy of HIIT in reversing the specific symptoms and risk factors of these cardiovascular pathologies is not well understood. HIIT is often perceived as very strenuous, which could render it unsafe for those at risk of or afflicted with CVD, but these issues are also yet to be reviewed. Furthermore, the optimal HIIT protocol for each of the CVD cohorts has not been established. Thus, the purpose of this review article is to (1) evaluate the efficacy of HIIT relative to MICT in the prevention and management of cardiovascular conditions, and (2) explore any potential safety issues surrounding the suitability and/or tolerability of HIIT for patients with CVD, and the potential optimal prescriptive variables of HIIT for application in the clinical environment. PMID- 27548689 TI - Electronic Cigarettes: Questions in the Mist. AB - In many parts of the world, electronic cigarettes (ECs) are marketed as a tool to assist users in attempts to quit smoking and are perceived to be a safer alternative to tobacco cigarettes. Numerous studies have suggested ECs may not be effective in achieving this goal and that the illusive "safety" of ECs can be enticing to consumers. The composition of the liquid solutions vaporized by these devices has not been fully disclosed and may not contain the actual advertised ingredients in the fractions reported. As this market has developed largely outside the oversight of an appropriate regulatory body, we are left to evaluate how ECs as a form of nicotine replacement therapy fit in the existing regulatory framework of conventional cigarettes and what the role of nicotine is in our society. PMID- 27548690 TI - Beta-Blocker Management of Cocaine-Induced Chest Pain. PMID- 27548691 TI - Wearable Cardioverter Defibrillators. AB - The use of implantable cardioverter defibrillators (ICD) has favorably impacted the prevention and treatment of sudden cardiac death (SCD) associated with ventricular arrhythmias. However, there are situations where an ICD cannot be immediately implanted, even though the patient is at high risk for SCD. The wearable cardioverter defibrillator (WCD) is a unique technology that can bridge this gap for patients. The WCD has been demonstrated to terminate ventricular tachycardia/fibrillation if worn and used correctly. With proper training, it is relatively easy to put on, maintain, and use. Most patients are compliant and are able to consistently wear the device. The WCD negates the infection risk or procedural complications associated with insertion and possible extraction of leads, as with an ICD. In terms of primary prevention of ventricular tachycardia/fibrillation in patients with a left ventricular ejection fraction <=35%, prospective, randomized studies evaluating the survival of patients utilizing the WCD will need to be performed before evidenced-based criteria for its use can be established. On the basis of current data, WCD use for those awaiting heart transplant, for those with ICD indications status post-ICD explant, and for high-risk SCD patients with possible reversible cardiomyopathy appears to be a reasonable approach on the basis of current data. PMID- 27548692 TI - Emerging Therapies for Inflammatory Bowel Diseases. AB - BACKGROUND: The past decade has seen important advances in the management of chronic inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis. The development of TNF antagonists, the recognition of interrupting lymphocyte trafficking as an effective treatment strategy, confirmation of the value of combination therapy, and the need, particularly in CD, for the treatment of high-risk patients early in the disease course are all fundamental concepts upon which the next generation of IBD treatment algorithms will be built. Emerging concepts that will continue to evolve and shape the field include an increased emphasis on personalized medicine (right drug, right dose, right time) and the development of new therapeutic classes. In this article, we review the clinical data and provide some insights into recent data regarding IBD therapies. KEY MESSAGES: In this article, we review the mechanism of action and data for novel therapies in IBD with particular focus on the evidence for agents targeting leukocyte trafficking, cytokine signaling, including interleukin-12/23 and the Janus kinase-signal transducers/activators of transcription pathway, and the emergence of antisense therapy for the treatment of IBD. CONCLUSIONS: Multiple new therapies are emerging for IBD; however, the potential positioning of these agents in treatment algorithms is difficult to predict in the absence of comparative effectiveness studies. PMID- 27548693 TI - Predictors of functional dependency in Parkinson's disease. AB - BACKGROUND: Functional dependency, the need for help in basic activities of daily living, is an important patient-oriented outcome. We aimed to describe the development of dependency in Parkinson's disease (PD) and identify independent prognostic factors for this outcome. METHODS: We analyzed data from the Parkinsonism Incidence in North-East Scotland (PINE) study, a prospective, community-based incident cohort of PD with ongoing follow-up. We described the development of dependency defined by a Schwab & England score of < 80% and a Barthel Index of <19. We identified the baseline predictors of dependency using multivariable Cox regression. RESULTS: In 198 patients with PD, the rate of development of dependency was 14 per 100 person years. Older age at diagnosis (hazard ratio for 10-year increase 2.23 [95% confidence interval 1.66-2.98]), greater smoking history (hazard ratio for 10-pack-year increase, 1.15 [1.04 1.26]), more severe axial impairment (hazard ratio for 5-point increase in sum of axial items from UPDRS scale, 1.78 [1.30-2.44]), and lower MMSE score (hazard ratio 0.88 [0.79-0.98]) were independently associated with a higher risk of dependency as defined by Schwab & England. Only older age (hazard ratio for 10 year increase 1.35 [1.04-1.76]) and severity of axial impairment (hazard ratio for 5-point increase 1.85 [1.31-2.62]) were associated with a higher risk of dependency as defined by the Barthel Index. Sex, deprivation, comorbidity, overall UPDRS motor score, and disease stage were not independently associated with dependency. CONCLUSION: This is the first community-based study of dependency in PD. There was a high rate of dependency development. Older age, more smoking, more axial impairment, and poorer cognition were independent predictors. (c) 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID- 27548694 TI - Posaconazole Therapeutic Drug Monitoring in a Regional Hospital Setting. AB - BACKGROUND: Posaconazole therapeutic drug monitoring (TDM) is recommended to promote effective antifungal prophylaxis, but its utility has yet to be optimized. Breakthrough invasive fungal infections have been reported with serum concentrations <700 mcg/L, but there is little evidence to determine the optimal serum concentration for efficacy or concentrations associated with toxicity. Challenges for effective monitoring are greater in settings without posaconazole TDM facilities because of the long turnaround time before receipt of results. METHODS: Thirty-eight TDM episodes were performed on 18 patients in a regional center in Australia during a 30-month period. Australian guidelines recommend a trough serum concentration of >=700 mcg/L. The response to concentrations below the recommendation threshold (700 mcg/L), the final serum plasma concentration for each patient, and the appropriateness of TDM were evaluated. RESULTS: A total of 19 (50%) concentrations were recorded to be < 700 mcg/L. Of these 19 concentrations, the drug dose was increased on only 4 occasions. Eleven of 18 patients (61%) had initial concentrations <700 mcg/L, with only 3 (27%) among those achieving final concentration >= 700 mcg/L; 5 patients with initial concentrations <700 mcg/L did not have any further TDM testing. Nine of the 18 (50%) patients had a final concentration <700 mcg/L. Five of 7 (71%) patients with initial concentrations >=700 mcg/L had further TDM with no reasoning documented. CONCLUSIONS: The results demonstrate a lack of confidence and consistency in ordering, interpreting, and following up posaconazole concentrations. Therefore, the use of TDM should be carefully considered, especially in regional centers. Such settings should consider the practicalities of posaconazole TDM and try to improve the process to ensure consistency and optimization of patient care. PMID- 27548695 TI - Marginal Structural Models to Assess Delays in Second-Line HIV Treatment Initiation in South Africa. AB - BACKGROUND: South African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure. METHODS: We include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second-line. RESULTS: 5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1-8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment <=100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6-12 months vs. 0-1.5 months = 1.47 (95% CI: 0.94-2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3-6 months vs. 0-1.5 months = 2.13 (95% CI: 1.01 4.47)). CONCLUSIONS: Even small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly. PMID- 27548696 TI - Redox-Active Esters in Fe-Catalyzed C-C Coupling. AB - Cross-couplings of alkyl halides and organometallic species based on single electron transfer using Ni and Fe catalyst systems have been studied extensively, and separately, for decades. Here we demonstrate the first couplings of redox active esters (both isolated and derived in situ from carboxylic acids) with organozinc and organomagnesium species using an Fe-based catalyst system originally developed for alkyl halides. This work is placed in context by showing a direct comparison with a Ni catalyst for >40 examples spanning a range of primary, secondary, and tertiary substrates. This new C-C coupling is scalable and sustainable, and it exhibits a number of clear advantages in several cases over its Ni-based counterpart. PMID- 27548697 TI - Breast Cancer Screening Interval: Risk Level May Matter. PMID- 27548699 TI - Emergency Department Use and Hospital Admissions Among Patients With End-Stage Renal Disease in the United States. PMID- 27548698 TI - One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections. AB - Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one tube-only standardized SDM approach that generates comprehensive collections of amino acid substitution variants, including scanning- and single site-multiple mutations. The approach combines unified mutagenic primer design with the mixing of multiple distinct primer pairs and/or plasmid templates to increase the yield of a single inverse-PCR mutagenesis reaction. Also, a user-friendly program for automatic design of standardized primers for Ala-scanning mutagenesis is made available. Experimental results were compared with a modeling approach together with stochastic simulation data. For single site-multiple mutagenesis purposes and for simultaneous mutagenesis in different plasmid backgrounds, combination of primer sets and/or plasmid templates in a single reaction tube yielded the distinct mutations in a stochastic fashion. For scanning mutagenesis, we found that a combination of overlapping primer sets in a single PCR reaction allowed the yield of different individual mutations, although this yield did not necessarily follow a stochastic trend. Double mutants were generated when the overlap of primer pairs was below 60%. Our results illustrate that one-tube-only SDM effectively reduces the number of reactions required in large-scale mutagenesis strategies, facilitating the generation of comprehensive collections of protein variants suitable for functional analysis. PMID- 27548700 TI - Comprehensive in Vitro Analysis of Acyltransferase Domain Exchanges in Modular Polyketide Synthases and Its Application for Short-Chain Ketone Production. AB - Type I modular polyketide synthases (PKSs) are polymerases that utilize acyl-CoAs as substrates. Each polyketide elongation reaction is catalyzed by a set of protein domains called a module. Each module usually contains an acyltransferase (AT) domain, which determines the specific acyl-CoA incorporated into each condensation reaction. Although a successful exchange of individual AT domains can lead to the biosynthesis of a large variety of novel compounds, hybrid PKS modules often show significantly decreased activities. Using monomodular PKSs as models, we have systematically analyzed the segments of AT domains and associated linkers in AT exchanges in vitro and have identified the boundaries within a module that can be used to exchange AT domains while maintaining protein stability and enzyme activity. Importantly, the optimized domain boundary is highly conserved, which facilitates AT domain replacements in most type I PKS modules. To further demonstrate the utility of the optimized AT domain boundary, we have constructed hybrid PKSs to produce industrially important short-chain ketones. Our in vitro and in vivo analysis demonstrated production of predicted ketones without significant loss of activities of the hybrid enzymes. These results greatly enhance the mechanistic understanding of PKS modules and prove the benefit of using engineered PKSs as a synthetic biology tool for chemical production. PMID- 27548701 TI - Flexible shrinkage estimation of subgroup effects through Dirichlet process priors. AB - The paradigm shift towards precision medicine reignited interest in determining whether there are differential treatment effects in subgroups of trial participants. Intrinsic to this problem is that any assessment of a differential treatment effect is predicated on being able to estimate the treatment response accurately while satisfying constraints of balancing the risk of overlooking an important subgroup with the potential to make a decision based on a false discovery. While shrinkage models have been widely used to improve accuracy of subgroup parameter estimates by leveraging the relationship between them, there is still a possibility that it can lead to excessively conservative or anti conservative results. This can possibly be due to the use of the normal distribution as prior, which forces outlying subjects to have their means over shrunk towards the population mean, and the data from such subjects may be excessively influential in estimation of both the overall mean response and the mean response for each subgroup, or a model misspecification due to unaccounted variation or clustering. To address this issue, we investigate the use of nonparametric Bayes, particularly Dirichlet process priors, to create a flexible shrinkage model. This model represents uncertainty in the prior distribution for the overall response while accommodating heterogeneity among individual subgroups. We simulated data to compare estimates when there is no differential subgroup effect and when there is a differential subgroup effect. In either of these scenarios, the flexible shrinkage model does not force estimates to shrink excessively when similarity of treatment effects is not supported but still retains the attractiveness of improved precision given by the narrower credible intervals. We also applied the same method to a dataset based on trials conducted for an antimicrobial therapy on several related indications. PMID- 27548702 TI - Rivaroxaban in Chronic Hemodialysis Patients: Clarification of an Editorial Error. PMID- 27548703 TI - Endobronchial Ultrasound Bronchoscopy to the Heart of the Matter. AB - Endobronchial ultrasound has been one of the success stories of the last decade, and the utility of the procedure continues to expand. Originally, it was developed for the staging and diagnosis of lung cancer, but its use rapidly expanded to other malignancies and even benign disease. We present the case of a patient originally referred with suspected endocarditis who was found to have a mass involving the right ventricle and the pulmonary outflow tract. Endobronchial ultrasound-guided biopsy was used to obtain a tissue diagnosis from the cardiac mass. PMID- 27548704 TI - Electron-Beam-Induced Antiphase Boundary Reconstructions in a ZrO2-LSMO Pillar Matrix System. AB - The availability of aberration correctors for the probe-forming lenses makes simultaneous modification and characterization of materials down to atomic scale inside a transmission electron microscopy (TEM) realizable. In this work, we report on the electron-beam-induced reconstructions of three types of antiphase boundaries (APBs) in a probe-aberration-corrected TEM. With the utilization of high-angle annular dark-field scanning transmission electron microscopy (STEM), annular bright-field STEM, and electron energy-loss spectroscopy, the motion of both heavy element Mn and light element O atomic columns under moderate electron beam irradiation are revealed at atomic resolution. Besides, Mn segregated in the APBs was observed to have reduced valence states which can be directly correlated with oxygen loss. Charge states of the APBs are finally discussed on the basis of these experimental results. This study provides support for the design of radiation-engineering solid-oxide fuel cell materials. PMID- 27548705 TI - Melt-driven mechanochemical phase transformations in moderately exothermic powder mixtures. AB - Usually, mechanochemical reactions between solid phases are either gradual (by deformation-induced mixing), or self-propagating (by exothermic chemical reaction). Here, by means of a systematic kinetic analysis of the Bi-Te system reacting to Bi2Te3, we establish a third possibility: if one or more of the powder reactants has a low melting point and low thermal effusivity, it is possible that local melting can occur from deformation-induced heating. The presence of hot liquid then triggers chemical mixing locally. The molten events are constrained to individual particles, making them distinct from self propagating reactions, and occur much faster than conventional gradual reactions. We show that the mechanism is applicable to a broad variety of materials systems, many of which have important functional properties. This mechanistic picture offers a new perspective as compared to conventional, gradual mechanochemical synthesis, where thermal effects are generally ignored. PMID- 27548706 TI - Fracture in sheets draped on curved surfaces. AB - Conforming materials to rigid substrates with Gaussian curvature-positive for spheres and negative for saddles-has proven a versatile tool to guide the self assembly of defects such as scars, pleats, folds, blisters, and liquid crystal ripples. Here, we show how curvature can likewise be used to control material failure and guide the paths of cracks. In our experiments, and unlike in previous studies on cracked plates and shells, we constrained flat elastic sheets to adopt fixed curvature profiles. This constraint provides a geometric tool for controlling fracture behaviour: curvature can stimulate or suppress the growth of cracks and steer or arrest their propagation. A simple analytical model captures crack behaviour at the onset of propagation, while a two-dimensional phase-field model with an added curvature term successfully captures the crack's path. Because the curvature-induced stresses are independent of material parameters for isotropic, brittle media, our results apply across scales. PMID- 27548707 TI - Transcription upregulation via force-induced direct stretching of chromatin. AB - Mechanical forces play critical roles in the function of living cells. However, the underlying mechanisms of how forces influence nuclear events remain elusive. Here, we show that chromatin deformation as well as force-induced transcription of a green fluorescent protein (GFP)-tagged bacterial-chromosome dihydrofolate reductase (DHFR) transgene can be visualized in a living cell by using three dimensional magnetic twisting cytometry to apply local stresses on the cell surface via an Arg-Gly-Asp-coated magnetic bead. Chromatin stretching depended on loading direction. DHFR transcription upregulation was sensitive to load direction and proportional to the magnitude of chromatin stretching. Disrupting filamentous actin or inhibiting actomyosin contraction abrogated or attenuated force-induced DHFR transcription, whereas activating endogenous contraction upregulated force-induced DHFR transcription. Our findings suggest that local stresses applied to integrins propagate from the tensed actin cytoskeleton to the LINC complex and then through lamina-chromatin interactions to directly stretch chromatin and upregulate transcription. PMID- 27548708 TI - Linear topology in amorphous metal oxide electrochromic networks obtained via low temperature solution processing. AB - Amorphous transition metal oxides are recognized as leading candidates for electrochromic window coatings that can dynamically modulate solar irradiation and improve building energy efficiency. However, their thin films are normally prepared by energy-intensive sputtering techniques or high-temperature solution methods, which increase manufacturing cost and complexity. Here, we report on a room-temperature solution process to fabricate electrochromic films of niobium oxide glass (NbOx) and 'nanocrystal-in-glass' composites (that is, tin-doped indium oxide (ITO) nanocrystals embedded in NbOx glass) via acid-catalysed condensation of polyniobate clusters. A combination of X-ray scattering and spectroscopic characterization with complementary simulations reveals that this strategy leads to a unique one-dimensional chain-like NbOx structure, which significantly enhances the electrochromic performance, compared to a typical three-dimensional NbOx network obtained from conventional high-temperature thermal processing. In addition, we show how self-assembled ITO-in-NbOx composite films can be successfully integrated into high-performance flexible electrochromic devices. PMID- 27548709 TI - Fiber Network Models Predict Enhanced Cell Mechanosensing on Fibrous Gels. AB - The propagation of mechanical signals through nonlinear fibrous tissues is much more extensive than through continuous synthetic hydrogels. Results from recent studies indicate that increased mechanical propagation arises from the fibrous nature of the material rather than the strain-stiffening property. The relative importance of different parameters of the fibrous network structure to this propagation, however, remains unclear. In this work, we directly compared the mechanical response of substrates of varying thickness subjected to a constant cell traction force using either a nonfibrous strain-stiffening continuum-based model or a volume-averaged fiber network model consisting of two different types of fiber network structures: one with low fiber connectivity (growth networks) and one with high fiber connectivity (Delaunay networks). The growth network fiber models predicted a greater propagation of substrate displacements through the model and a greater sensitivity to gel thickness compared to the more connected Delaunay networks and the nonlinear continuum model. Detailed analysis of the results indicates that rotational freedom of the fibers in a network with low fiber connectivity is critically important for enhanced, long-range mechanosensing. Our findings demonstrate the utility of multiscale models in predicting cells mechanosensing on fibrous gels, and they provide a more complete understanding of how cell traction forces propagate through fibrous tissues, which has implications for the design of engineered tissues and the stem cell niche. PMID- 27548710 TI - 14-3-3zeta Mediates Tau Aggregation in Human Neuroblastoma M17 Cells. AB - Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3zeta is bound to tau in the PHFs and when incubated in vitro with 14-3-3zeta, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445-6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3beta or PKA does not cause tau aggregation, but promotes 14-3-3zeta-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3zeta-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3zeta and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3zeta-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3zeta. PMID- 27548711 TI - Manipulating the sequence of food ingestion improves glycemic control in type 2 diabetic patients under free-living conditions. AB - Lipid and protein ingested before carbohydrate reduce postprandial hyperglycemia. We tested feasibility, safety and clinical efficacy of manipulating the sequence of nutrient ingestion in patients with type 2 diabetes (T2D). After a 4-week run in, 17 T2D patients were randomized to either a control diet (CD) or to an experimental diet (ED) allowing the consumption of high-carbohydrate foods only after high-protein and high-fat foods at each main meal (lunch+dinner). Both diets were accurately followed and neutral on arterial blood pressure, plasma lipids and indices of hepatic and kidney function. After 8 weeks, in spite of a similar reduction of body weight (ED -1.9 95% confidence interval (-3.4/-0.4)kg, P<0.03; CD -2.0 (-3.6/-0.5)kg, P<0.02) and waist circumference (ED -2.9 (-4.3/ 1.5)cm, P<0.002; CD -3.3 (-5.9/-0.7)cm, P<0.02), the ED only was associated with significant reductions of HbA1c (-0.3 (-0.50/-0.02)%, P<0.04), fasting plasma glucose (-1.0 (-1.8/-0.3)mmol l(-1), P<0.01), postprandial glucose excursions (lunch -1.8 (-3.2/-0.4)mmol l(-1), P<0.01; dinner: -1.0 (-1.9/-0.1)mmol l(-1), P<0.04) and other indices of glucose variability (s.d.: -0.5 (-0.7/-0.2)mmol l( 1), P<0.02; Coefficient of variation: -6.6 (-10.4/-2.7)%, P<0.02). When compared with the CD, the ED was associated with lower post-lunch glucose excursions (P<0.02) and lower glucose coefficients of variation (P<0.05). Manipulating the sequence of nutrient ingestion might reveal a rapid, feasible, economic and safe strategy for optimizing glucose control in T2D. PMID- 27548712 TI - Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood. AB - OBJECTIVES: In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM. METHODS: In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry - BORIS who were ?18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l(-1)) and WHO (6.1 mmol l(-1)). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l(-1)). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry. RESULTS: The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52-46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87-7.45) compared with those who had fasting glucose levels <5.6 mmol l(-1). A fasting glucose level of 5.6-6.0 mmol l(-1), that is, the IFG interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84 3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50-6.52). More severe degree of obesity also increased the future T2DM risk. CONCLUSION: IFG according to WHO and elevated HbA1c (39-48 mmol l(-1)), but not the additional fasting glucose interval added by ADA (5.6-6.0 mmol l(-1)), can be considered as prediabetes in the obese pediatric population in Sweden. PMID- 27548713 TI - Ligand "Brackets" for Ga-Ga Bond. AB - The reactivity of digallane (dpp-Bian)Ga-Ga(dpp-Bian) (1) (dpp-Bian = 1,2 bis[(2,6-diisopropylphenyl)imino]acenaphthene) toward acenaphthenequinone (AcQ), sulfur dioxide, and azobenzene was investigated. The reaction of 1 with AcQ in 1:1 molar ratio proceeds via two-electron reduction of AcQ to give (dpp Bian)Ga(MU2-AcQ)Ga(dpp-Bian) (2), in which diolate [AcQ](2-) acts as "bracket" for the Ga-Ga bond. The interaction of 1 with AcQ in 1:2 molar ratio proceeds with an oxidation of the both dpp-Bian ligands as well as of the Ga-Ga bond to give (dpp-Bian)Ga(MU2-AcQ)2Ga(dpp-Bian) (3). At 330 K in toluene complex 2 decomposes to give compounds 3 and 1. The reaction of complex 2 with atmospheric oxygen results in oxidation of a Ga-Ga bond and affords (dpp-Bian)Ga(MU2-AcQ)(MU2 O)Ga(dpp-Bian) (4). The reaction of digallane 1 with SO2 produces, depending on the ratio (1:2 or 1:4), dithionites (dpp-Bian)Ga(MU2-O2S-SO2)Ga(dpp-Bian) (5) and (dpp-Bian)Ga(MU2-O2S-SO2)2Ga(dpp-Bian) (6). In compound 5 the Ga-Ga bond is preserved and supported by dithionite dianionic bracket. In compound 6 the gallium centers are bridged by two dithionite ligands. Both 5 and 6 consist of dpp-Bian radical anionic ligands. Four-electron reduction of azobenzene with 1 mol equiv of digallane 1 leads to complex (dpp-Bian)Ga(MU2-NPh)2Ga(dpp-Bian) (7). Paramagnetic compounds 2-7 were characterized by electron spin resonance spectroscopy, and their molecular structures were established by single-crystal X ray analysis. Magnetic behavior of compounds 2, 5, and 6 was investigated by superconducting quantum interference device technique in the range of 2-295 K. PMID- 27548715 TI - When emotion and expression diverge: The social costs of Parkinson's disease. AB - INTRODUCTION: Patients with Parkinson's disease (PD) are perceived more negatively than their healthy peers, yet it remains unclear what factors contribute to this negative social perception. METHOD: Based on a cohort of 17 PD patients and 20 healthy controls, we assessed how naive raters judge the emotion and emotional intensity displayed in dynamic facial expressions as adults with and without PD watched emotionally evocative films (Experiment 1), and how age matched peers naive to patients' disease status judge their social desirability along various dimensions from audiovisual stimuli (interview excerpts) recorded after certain films (Experiment 2). RESULTS: In Experiment 1, participants with PD were rated as significantly more facially expressive than healthy controls; moreover, ratings demonstrated that PD patients were routinely mistaken for experiencing a negative emotion, whereas controls were rated as displaying a more positive emotion than they reported feeling. In Experiment 2, results showed that age-peers rated PD patients as significantly less socially desirable than control participants. Specifically, PD patients were rated as less involved, interested, friendly, intelligent, optimistic, attentive, and physically attractive than healthy controls. CONCLUSIONS: Taken together, our results point to a disconnect between how PD patients report feeling and attributions that others make about their emotions and social characteristics, underlining significant social challenges of the disease. In particular, changes in the ability to modulate the expression of negative emotions may contribute to the negative social impressions that many PD patients face. PMID- 27548714 TI - Framing Young Childrens Oral Health: A Participatory Action Research Project. AB - BACKGROUND AND OBJECTIVES: Despite the widespread acknowledgement of the importance of childhood oral health, little progress has been made in preventing early childhood caries. Limited information exists regarding specific daily-life and community-related factors that impede optimal oral hygiene, diet, care, and ultimately oral health for children. We sought to understand what parents of young children consider important and potentially modifiable factors and resources influencing their children's oral health, within the contexts of the family and the community. METHODS: This qualitative study employed Photovoice among 10 English-speaking parents of infants and toddlers who were clients of an urban WIC clinic in North Carolina. The primary research question was: "What do you consider as important behaviors, as well as family and community resources to prevent cavities among young children?" Five group sessions were conducted and they were recorded, transcribed verbatim and analyzed using qualitative research methodology. Inductive analyses were based on analytical summaries, double coding, and summary matrices and were done using Atlas.ti.7.5.9 software. FINDINGS: Good oral health was associated with avoidance of problems or restorations for the participants. Financial constraints affected healthy food and beverage choices, as well as access to oral health care. Time constraints and occasional frustration related to children's oral hygiene emerged as additional barriers. Establishment of rules/routines and commitment to them was a successful strategy to promote their children's oral health, as well as modeling of older siblings, cooperation among caregivers and peer support. Community programs and organizations, social hubs including playgrounds, grocery stores and social media emerged as promising avenues for gaining support and sharing resources. CONCLUSIONS: Low-income parents of young children are faced with daily life struggles that interfere with oral health and care. Financial constraints are pervasive, but parents identified several strategies involving home care and community agents that can be helpful. Future interventions aimed to improve children's oral health must take into consideration the role of families and the communities in which they live. PMID- 27548716 TI - The development of agents targeting the BCR-ABL tyrosine kinase as Philadelphia chromosome-positive acute lymphoblastic leukemia treatment. AB - INTRODUCTION: In Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL. Furthermore, this paper highlights the impact of this knowledge on the development of a targeted therapy approach in Ph+ ALL and the obstacles for the successful treatment with these drugs. Expert opinion: Identifying key components involved in disease pathogenesis may lead to new approaches that might overcome resistance mediated to the BCR-ABL TKIs. In a near future, the authors believe that monoclonal antibodies and immunotherapy should also be combined with TKIs and up front chemotherapy for the successful treatment of ALL. PMID- 27548719 TI - Isolating the Photovoltaic Junction: Atomic Layer Deposited TiO2-RuO2 Alloy Schottky Contacts for Silicon Photoanodes. AB - We synthesized nanoscale TiO2-RuO2 alloys by atomic layer deposition (ALD) that possess a high work function and are highly conductive. As such, they function as good Schottky contacts to extract photogenerated holes from n-type silicon while simultaneously interfacing with water oxidation catalysts. The ratio of TiO2 to RuO2 can be precisely controlled by the number of ALD cycles for each precursor. Increasing the composition above 16% Ru sets the electronic conductivity and the metal work function. No significant Ohmic loss for hole transport is measured as film thickness increases from 3 to 45 nm for alloy compositions >= 16% Ru. Silicon photoanodes with a 2 nm SiO2 layer that are coated by these alloy Schottky contacts having compositions in the range of 13-46% Ru exhibit average photovoltages of 525 mV, with a maximum photovoltage of 570 mV achieved. Depositing TiO2-RuO2 alloys on nSi sets a high effective work function for the Schottky junction with the semiconductor substrate, thus generating a large photovoltage that is isolated from the properties of an overlying oxygen evolution catalyst or protection layer. PMID- 27548720 TI - Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction. AB - BACKGROUND: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). KEY MESSAGES: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease. CONCLUSIONS: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies. PMID- 27548721 TI - Well-Being and Institutional Care in Older Adults: Cross-Sectional and Time Effects of Provided and Received Support. AB - BACKGROUND: The aim of the study was to examine the cross-sectional and longitudinal effects of provided and received support on older adults' subjective well-being (positive affect and depression) and to examine whether being a recipient of institutional care moderates these effects. METHODS: Social support (provided and received), positive affect, and depressive symptoms were assessed twice (at baseline and 1 month later) for 277 older adults (age 77.39 +/- 9.20 years, 67.50% women, 65% residents of an institutional care facility). FINDINGS: Two structural equation models were analyzed: cross-sectional (at baseline) and longitudinal (after 1 month). The first model revealed a significant positive relationship between providing and receiving support and positive affect, and a negative relationship between receiving support and depression. However, being a recipient of institutional care appeared to be a significant moderator in the longitudinal model. Specifically, the findings indicated effects of both providing and receiving support on positive affect but only for noninstitutionalized older adults. DISCUSSION: Although both types of support may be beneficial for older adults, their effects depend on the nature of social exchange and the dimensions of well-being. This suggests that such factors should be systematically investigated in future research. PMID- 27548723 TI - The Post-Embargo Open Access Citation Advantage: It Exists (Probably), Its Modest (Usually), and the Rich Get Richer (of Course). AB - Many studies show that open access (OA) articles-articles from scholarly journals made freely available to readers without requiring subscription fees-are downloaded, and presumably read, more often than closed access/subscription-only articles. Assertions that OA articles are also cited more often generate more controversy. Confounding factors (authors may self-select only the best articles to make OA; absence of an appropriate control group of non-OA articles with which to compare citation figures; conflation of pre-publication vs. published/publisher versions of articles, etc.) make demonstrating a real citation difference difficult. This study addresses those factors and shows that an open access citation advantage as high as 19% exists, even when articles are embargoed during some or all of their prime citation years. Not surprisingly, better (defined as above median) articles gain more when made OA. PMID- 27548722 TI - The Proprotein Convertase Furin Contributes to Rhabdomyosarcoma Malignancy by Promoting Vascularization, Migration and Invasion. AB - The proprotein convertase (PC) furin cleaves precursor proteins, an important step in the activation of many cancer-associated proteins. Substrates of furin and furin-like PCs play a role in proliferation, metastasis and invasion. Some of them are involved in the progression of the pediatric soft tissue sarcoma rhabdomyosarcoma (RMS). In this study, we show that PCs, and in particular furin, are expressed in RMS cell lines. To investigate the functional role of furin, we generated RMS cell lines with modulated furin activity. Silencing or stable inhibition of furin delayed tumor growth in Rh30 and RD xenografts in vivo, and was correlated with lower microvessel density. Reduced furin activity also decreased migration and invasion abilities in vitro, and inhibition of furin in RMS cells diminished processing of IGF1R, VEGF-C, PDGF-B and MT1-MMP, leading to lower levels of mature proteins. Furthermore, we found that furin activity is required for proper IGF signaling in RMS cells, as furin silencing resulted in reduced phosphorylation of Akt upon IGF1 stimulation. Taken together, our results suggest that furin plays an important role in the malignant phenotype of RMS cells by activating proteins involved in tumor growth and vascularization, metastasis and invasion. PMID- 27548724 TI - Any Future for Fecal Microbiota Transplantation as Treatment Strategy for Inflammatory Bowel Diseases? AB - Fecal microbiota transplantation (FMT) is a novel therapeutic procedure aiming at restoring a normal intestinal microbiota by application of fecal microorganisms from a healthy subject into the gastrointestinal tract of a patient. FMT is the most effective treatment for recurrent Clostridium difficile infections (CDI). These infections also occur in patients with inflammatory bowel diseases (IBDs), where case series demonstrated a successful treatment of CDI by FMT in 83-92% of patients. The effect of FMT on the activity of IBD has mainly been investigated in ulcerative colitis (UC) patients, including 3 randomized controlled trials. So far, 2 randomized controlled trials showed a superiority of FMT compared to placebo in inducing remission in UC, while 1 study found no significant difference to placebo. The variation in response to FMT between these studies as well as in the uncontrolled trials might be explained by many differences in the way of FMT application, patient pretreatment and patient and donor selection. The data for the use of FMT in Crohn's disease and pouchitis are sparse; currently, no conclusion can be drawn regarding the effectiveness of FMT in these indications. It needs to be noted that cases of IBD activation after FMT have been reported. So far, FMT can only be recommended to be used for the treatment of concomitant CDI in IBD in clinical practice. For treating IBD irrespective of CDI, FMT should be only used in clinical trials. Current forms of FMT, especially protocols using repeated application, are very time and personnel consuming. Future trends are the use of defined stable microbiota preparations, in particular oral preparations, which will enable better and larger controlled trails for investigating FMT in IBD. PMID- 27548726 TI - Theory of solid effect and cross effect dynamic nuclear polarization with half integer high-spin metal polarizing agents in rotating solids. AB - Dynamic nuclear polarization (DNP) is a powerful method to enhance sensitivity especially of solid-state magic-angle spinning (MAS) NMR by up to several orders of magnitude. The increased interest both from a practical as well as theoretical viewpoint has spawned several fields of active research such as the development of new polarizing agents with improved or unique properties and description of the underlying DNP mechanisms such as solid effect (SE) and cross effect (CE). Even though a novel class of unique polarizing agents based on high-spin metal ions such as Gd(iii) and Mn(ii) has already been utilized for MAS DNP a theoretical description of the involved DNP mechanism is still incomplete. Here, we review several aspects of DNP-relevant electron-paramagnetic resonance (EPR) properties of the general class of these half-integer high-spin metal ions with isotropic Zeeman interaction but significant zero-field splitting (ZFS). While the SE can be relatively easily described similar to that of a S = 1/2 system and is assumed to be effective only for polarizing agents featuring a narrow central EPR transitions (i.e., mS = -1/2 -> +1/2) with respect to the nuclear Larmor frequency, the CE between two high-spin ions requires a more detailed theoretical investigation due to a multitude of possible transitions and matching conditions. This is especially interesting in light of recent understanding of CE being induced by MAS-driven level anti-crossings (LACs) between dipolar-coupled electron spins. We discuss the requirements of such CE-enabling LACs to occur due to anisotropy of ZFS, the expected adiabaticity, and the resulting possibilities of high-spin metal ion pairs to act as polarizing agents for DNP. This theoretical description serves as a framework for a detailed experimental study published directly following this work. PMID- 27548725 TI - More Than a Touch of Gray: Embracing Uncertainty in the Intensive Care Unit. PMID- 27548727 TI - A Prospective Blinded Comparison of Video Capsule Endoscopy Versus Computed Tomography Enterography in Potential Small Bowel Bleeding: Clinical Utility of Computed Tomography Enterography. AB - GOALS: To compare the efficacy of video capsule endoscopy (VCE) with computed tomography enterography (CTE) in potential small bowel (SB) bleeding, and to identify factors predictive of a high diagnostic yield for CTE. BACKGROUND: In potential SB bleeding, CTE potentially detects some lesions missed by VCE, but few data have determined its clinical utility. STUDY: Consecutive patients with potential SB bleeding were prospectively enrolled. All underwent VCE and CTE within a 1-week interval. Definitive diagnoses were made by surgery or enteroscopy, except when a strategy of VCE and conservative management was suitable. The diagnostic yields and sensitivities of each investigation were measured. RESULTS: Fifty-two patients were recruited (41 with overt and 11 with occult bleeding); 36 received a definitive diagnosis. The diagnostic yields and sensitivities of VCE and CTE were 59.6% and 30.8% (P=0.004), and 72.2% and 44.4% (P=0.052), respectively. The combined sensitivity of VCE and CTE (88.9%) was significantly greater than VCE (P=0.03) or CTE (P<0.01) alone. VCE was better for ulcers, enteritis, and angiodysplasia, whereas CTE was better for tumors and Meckel diverticula. Age below 40 years and severe bleeding were associated with a higher diagnostic yield for CTE [odds ratios (95% confidence interval)=7.3 (1.04 51.4), P=0.046 and 6.1 (1.4-25.5), P=0.014, respectively]. CONCLUSIONS: Both investigations complement each other in the diagnosis of potential SB bleeding. CTE should be considered when VCE is negative. Age below 40 years and severe bleeding were independent predictors of a higher diagnostic yield for CTE. PMID- 27548728 TI - The Symptoms Related to Irritable Bowel Syndrome and Organic Disease. PMID- 27548729 TI - Use of Wireless Capsule Endoscopy for the Diagnosis and Grading of Esophageal Varices in Patients With Portal Hypertension: A Systematic Review and Meta Analysis. AB - INTRODUCTION: Esophageal variceal bleeding is a severe complication of portal hypertension with significant morbidity and mortality. Although traditional screening and grading of esophageal varices has been performed by endogastroduodenoscopy (EGD), wireless video capsule endoscopy provides a minimally invasive alternative that may improve screening and surveillance compliance. AIM OF THE STUDY: The aim of the study was to perform a systematic review and structured meta-analysis of all eligible studies to evaluate the efficacy of wireless capsule endoscopy for screening and diagnosis of esophageal varices among patients with portal hypertension. METHODS: Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through December 2015. Bivariate and hierarchical models were used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence region. Bias of included studies was assessed using the quality assessment of diagnostic accuracy studies-2. RESULTS: Seventeen studies from 2005 to 2015 were included in this meta-analysis (n=1328). The diagnostic accuracy of wireless capsule endoscopy in the diagnosis of esophageal varices was 90% [95% confidence interval (CI), 0.88-0.93]. The diagnostic pooled sensitivity and specificity were 83% (95% CI, 0.76-0.89) and 85% (95% CI, 0.75-0.91), respectively. The diagnostic accuracy of wireless capsule endoscopy for the grading of medium to large varices was 92% (95% CI, 0.90-0.94). The pooled sensitivity and specificity were 72% (95% CI, 0.54-0.85) and 91% (95% CI, 0.86-0.94), respectively, for the grading of medium to large varices. The use of capsule demonstrated only mild adverse events. A sensitivity analysis limited to only high quality studies revealed similar results. DISCUSSION: Wireless esophageal capsule endoscopy is well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension. The sensitivity of capsule endoscopy is not currently sufficient to replace EGD as a first exploration in these patients, but given its high accuracy, it may have a role in cases of refusal or contraindication to EGD. PMID- 27548730 TI - Endoscopic Management of Pancreatic Fluid Collections. AB - Pancreatic fluid collections (PFCs) may develop due to inflammation secondary to acute and/or chronic pancreatitis, trauma, surgery, or obstruction from solid or cystic neoplasms. PFCs can be drained percutaneously, surgically, or endoscopically with endoscopic ultrasound-guided cyst gastrostomy and/or transpapillary drainage through endoscopic retrograde cholangiopancreatography. There has been a paradigm shift in the endoscopic management of PFCs in the past few years with newer techniques including utilization of self-expanding metal stents and multiport devices. This review is a comprehensive update on the classification of PFC, indications for drainage, optimal approach, and techniques. PMID- 27548731 TI - Chronic Abdominal Wall Pain: An Under-Recognized Diagnosis Leading to Unnecessary Testing. AB - Chronic abdominal wall pain (CAWP) refers to a condition wherein pain originates from the abdominal wall itself rather than the underlying viscera. According to various estimates, 10% to 30% of patients with chronic abdominal pain are eventually diagnosed with CAWP, usually after expensive testing has failed to uncover another etiology. The most common cause of CAWP is anterior cutaneous nerve entrapment syndrome. The diagnosis of CAWP is made using an oft-forgotten physical examination finding known as Carnett's sign, where focal abdominal tenderness is either the same or worsened during contraction of the abdominal musculature. CAWP can be confirmed by response to trigger point injection of local anesthetic. Once diagnosis is made, treatment ranges from conservative management to trigger point injection and in refractory cases, even surgery. This review provides an overview of CAWP, discusses the cost and implications of a missed diagnosis, compares somatic versus visceral innervation, describes the pathophysiology of nerve entrapment, and reviews the evidence behind available treatment modalities. PMID- 27548732 TI - The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial. AB - BACKGROUND AND AIMS: Patients with fibromyalgia frequently present with symptoms similar to those experienced by patients with gluten-related disorders, raising the possibility that a subgroup of these patients could be experiencing underlying gluten sensitivity. This study aimed to evaluate the effects of a gluten-free diet (GFD) compared with a hypocaloric diet (HCD) among patients with fibromyalgia. METHODS: Adult patients diagnosed with fibromyalgia were randomly allocated to receive a GFD or a HCD over a 24-week period. The primary outcome measure was the change in the number of gluten sensitivity symptoms. The following secondary outcomes were evaluated: body mass index, Revised Fibromyalgia Impact Questionnaire, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Beck Depression Inventory-II, State-Trait Anxiety Inventory, Short Form Health Survey, Patient Global Impression Scale of Severity, Patient Global Impression Scale of Improvement, and adverse events. RESULTS: Seventy-five subjects were randomly allocated to receive either a GFD (n=35) or an HCD (n=40). The least squares mean change in the total number of gluten sensitivity symptoms from baseline did not differ significantly between the GFD and HCD groups ( 2.44+/-0.40 for the GFD; -2.10+/-0.37 for the HCD; P=0.343). Similarly, the 2 dietary interventions did not differ in any of the remaining measured secondary outcomes. Both dietary interventions were well tolerated. CONCLUSIONS: Both dietary interventions were associated with similar beneficial outcomes in reducing gluten sensitivity symptoms and other secondary outcomes. However, despite its specificity, GFD was not superior to HCD in reducing the number of gluten sensitivity symptoms or secondary outcomes. PMID- 27548733 TI - Extrapancreatic Necrosis in Acute Pancreatitis. PMID- 27548734 TI - Use of Sofosbuvir-Based Treatment of Chronic Hepatitis C in Liver Transplant Recipients on Hemodialysis. AB - BACKGROUND: The use of direct acting agents has changed the management paradigm of hepatitis C (HCV) in liver transplant (LT) recipients. However, the appropriate antiviral regimen in LT recipients on hemodialysis (HD) remains unclear. METHODS: We retrospectively evaluated the safety and efficacy of sofosbuvir-based LT recipients on HD followed at the University of California Los Angeles. RESULTS: Twelve LT recipients on HD were treated for recurrent HCV with sofosbuvir-based therapy. Indications for antiviral therapy included fibrosing cholestatic hepatitis, symptomatic cryoglobulinemia, and recurrent HCV. The causes of renal failure included hepatorenal syndrome, acute tubular necrosis and cryoglobulinemia. Of those who were not on dialysis at the time of transplantation, the mean creatinine (+/-SD) was 1.7 (+/-0.8) mg/dL. The mean age (+/-SD) of the cohort was 62.2 (+/-6.0) years. Most recipients were male (67%) and infected with genotype 1 (83%). Baseline alanine aminotransferase, total bilirubin, hemoglobin and HCV RNA values (+/-SD) were 53.2 (+/-59.4) IU/L, 3.2 (+/-5.5) mg/dL, 10.5 (+/-1.8) g/dL, and 30,499,500 (+/-29,655,754) IU/mL. HCV RNA levels were undetectable in all recipients at the end of therapy. The trough mean (+/-SD) hemoglobin of patients on treatment and on HD was 8.4 (+/-2.3). The sustained viral response was 58% (7/12), and the overall patient survival was 42%. All the deaths occurred a mean (+/-SD) after 5.4 (+/-3.6) months after treatment was completed. CONCLUSIONS: All patients achieved viral suppression from therapy, and over half the recipients achieved a sustained virological response. A high mortality underscores the necessity of starting antiviral treatment sooner in LT recipients and the need for larger cohort studies. PMID- 27548735 TI - Sedation and Afternoon Placement of the 48-Hour Wireless Ambulatory pH Capsule Results in More Reflux on the First Day. AB - BACKGROUND: A 48-hour wireless capsule results often vary from the first to second day. Previous investigations comparing discrepant acid reflux readings have yielded variable results. In this study we investigated differences in data obtained on day 1 versus day 2, and the effect of time of capsule placement on discrepancies. METHODS: We performed a retrospective cohort study. Patients undergoing a 48-hour wireless capsule study between January 2012 through November 2013 were eligible for inclusion. We collected reflux data for each patient and calculated the proportion of patients in four groups based on abnormal DeMeester score groups (+/+, -/+, +/-, -/-). We placed patients into morning placement or afternoon placement categories and calculated the proportions of patients with various DeMeester score discrepancies. KEY RESULTS: This study evaluated 229 patients. The mean day 1 DeMeester score was 28.38 and the mean day 2 DeMeester score was 23.24 (P<0.0001). The mean day 1 DeMeester score in the morning group was 24.9 and 31.7 in the afternoon group (P<0.05). The mean total DeMeester score in the morning placement group was 23.1 and 30.6 in the afternoon group (P<0.05). Twenty-five percent of afternoon patients had a +day 1/-day 2 DeMeester discordance, whereas only 12% of morning placement patients had this discordance (P=0.26). CONCLUSIONS: Afternoon capsule placement is associated with a significantly increased amount of acid reflux on day 1. Approximately 10% of 48 hour esophageal wireless monitoring studies may falsely overestimate reflux when the capsule is placed in the afternoon. Capsule placement should ideally be performed in the morning. PMID- 27548736 TI - Moving Beyond Univariate Post-Hoc Testing in Exercise Science: A Primer on Descriptive Discriminate Analysis. AB - : There has been a recent call to improve data reporting in kinesiology journals, including the appropriate use of univariate and multivariate analysis techniques. For example, a multivariate analysis of variance (MANOVA) with univariate post hocs and a Bonferroni correction is frequently used to investigate group differences on multiple dependent variables. However, this univariate approach decreases power, increases the risk for Type 1 error, and contradicts the rationale for conducting multivariate tests in the first place. PURPOSE: The purpose of this study was to provide a user-friendly primer on conducting descriptive discriminant analysis (DDA), which is a post-hoc strategy to MANOVA that takes into account the complex relationships among multiple dependent variables. METHOD: A real-world example using the Statistical Package for the Social Sciences syntax and data from 1,095 middle school students on their body composition and body image are provided to explain and interpret the results from DDA. RESULTS: While univariate post hocs increased the risk for Type 1 error to 76%, the DDA identified which dependent variables contributed to group differences and which groups were different from each other. For example, students in the very lean and Healthy Fitness Zone categories for body mass index experienced less pressure to lose weight, more satisfaction with their body, and higher physical self-concept than the Needs Improvement Zone groups. However, perceived pressure to gain weight did not contribute to group differences because it was a suppressor variable. CONCLUSION: Researchers are encouraged to use DDA when investigating group differences on multiple correlated dependent variables to determine which variables contributed to group differences. PMID- 27548737 TI - Long noncoding RNAs to predict survival in acute myeloid leukemia: a step toward personalized medicine? PMID- 27548740 TI - Outcome of Benign Acute Childhood Myositis: The Experience of 2 Large Tertiary Care Pediatric Hospitals. AB - OBJECTIVE: The aims of the study were to determine the evolution of benign acute childhood myositis in children and to assess the relationship between creatine phosphokinase (CPK) values and myoglobinuria. STUDY DESIGN: A retrospective study of patients with benign acute childhood myositis seen in 2 tertiary care university-affiliated pediatric hospitals during overlapping 4-year periods. METHODS: Demographic data, historical details, clinical, and laboratory results were extracted from the charts of children younger than 16 years with a CPK greater than 3 times normal. Complications, treatments, and outcomes were recorded. RESULTS: Fifty-four children were included, 43 (80%) were male, and mean age was 7.3 years (median [range], 6 [3-16] years), none showed abnormal neurological findings, manifested hematuria, or developed renal failure. Mean CPK level at presentation was 1872 IU/L (range, 511-8086 IU/L). None developed renal failure, and there were no adverse outcomes on follow-up. CONCLUSIONS: Acute childhood myositis is a predominantly benign disease. Neurological examination is usually normal and rhabdomyolysis is rare. Although severe pathological comorbid conditions must be excluded, a complete history and examination, coupled with simple blood and urine tests, can help minimize unnecessary diagnostic investigations. PMID- 27548738 TI - West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1 2B Polymorphisms. AB - West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3 249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells. PMID- 27548741 TI - Peer-Reviewed Journal Publication of Abstracts Presented at an International Emergency Medicine Scientific Meeting: Outcomes and Comparison With the Previous Meeting. AB - Scientific presentations at professional organization meetings have long been recognized as a method of providing up-to-date and novel information to both the medical and scientific community. After abstract presentation at a medical conference, the subsequent publication rate of full-text articles is variable, and few studies have examined this topic with respect to international emergency medicine conferences. This study's goals were to determine the publication rate of articles resulting from abstracts presented at the 12th International Conference on Emergency Medicine 2008 in San Francisco, Calif, and to compare this with data from the previous International Conference on Emergency Medicine 2006 conference in Halifax, Nova Scotia, Canada. We found a reduction in publication rate from 33.2% in 2006 to 22.8% in 2008 and that the host country furnished a greater proportion of the abstracts. It would be interesting to examine how these potential trends played out over more extended periods. PMID- 27548739 TI - Renal ischemia and reperfusion assessment with three-dimensional hyperpolarized 13 C,15 N2-urea. AB - PURPOSE: The aim of this work was to investigate whether hyperpolarized 13 C,15 N2 -urea can be used as an imaging marker of renal injury in renal unilateral ischemic reperfusion injury (IRI), given that urea is correlated with the renal osmotic gradient, which describes the renal function. METHODS: Hyperpolarized three-dimensional balanced steady-state 13 C magnetic resonance imaging (MRI) experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements were performed in rats subjected to unilateral renal ischemia for 60-minute and 24-hour reperfusion. RESULTS: We revealed a significant reduction in the intrarenal gradient in the ischemic kidney in agreement with cortical injury markers neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, as well as functional kidney parameters. CONCLUSION: Hyperpolarized functional 13 C,15 N2 urea MRI can be used to successfully detect changes in the intrarenal urea gradient post-IRI, thereby enabling in vivo monitoring of the intrarenal functional status in the rat kidney. Magn Reson Med 76:1524-1530, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27548742 TI - Retropharyngeal Abscess and Mediastinitis in a Well-Appearing Infant With Prolonged Fever. AB - Fever is a common presenting chief complaint in the pediatric emergency department. We report the case of a well-appearing 11-month-old female with 2 weeks of daily fevers who was found to have an extensive retropharyngeal abscess with mediastinal and extrapleural extension. We review the literature on retropharyngeal abscesses and mediastinitis in children and note that this patient is unusual as she presented with such extensive disease with minimal symptoms. This case demonstrates the importance of a thorough history and broad differential diagnosis when evaluating children presenting prolonged fevers. PMID- 27548743 TI - Cross-sectional Survey of Canadian Pediatric Critical Care Transport. AB - OBJECTIVES: This study aimed to better understand the unique aspects of pediatric critical care transport programs across Canada by characterizing the current workforce of each transport program. METHODS: A cross-sectional questionnaire was sent to the 13 medical directors of Canada's pediatric critical care transport teams, and to 2 nonhospital-affiliated transport services. If a children's hospital did not have a dedicated team for pediatric transport, the regional transport team providing this service was identified. RESULTS: Eight of the 13 pediatric intensive care units surveyed have unit-based pediatric transport teams. The median annual transport volume for the 8 hospital-based teams was 371 (range, 45-2300) with a total of 5686 patients being transported annually. Among patients transported by the 8 teams, 45% (2579 patients) were pediatric patients (older than 28 days and younger than 18 years) and 40% (1022 patients) of the pediatric patients were admitted to the pediatric intensive care units. Eighty eight percent of the responding teams also transported neonates (older than 28 days), and 38% transported premature infants.A team composition of registered nurse-respiratory therapist-physician was used by 6/13 teams (75%); however, it accounted for only a small proportion of the transports for most of the teams (median, 2%; range, 2%-100%).The average transport time from dispatch (from team home site) to arrival at receiving facility was reported by 6 teams, and has a median of 195 minutes (range, 90-360 minutes). The median distance from home site to the farthest referral site in the catchment area was 700 km (range, 15-2500 km). CONCLUSIONS: This is the first Canadian nationwide study of pediatric critical care transport programs. It revealed a complexity and variability in transport team demographics, transport volume, team composition, and decision making process. PMID- 27548744 TI - Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: a mathematical model. AB - Despite tremendous advances in the field of tissue engineering, a number of obstacles remain that hinder its successful translation to the clinic. One challenge that relates to the use of cells encapsulated in a hydrogel is identifying a hydrogel design that can provide an appropriate environment for cells to successfully synthesize and deposit new matrix molecules while providing a mechanical support that can resist physiological loads at the early stage of implementation. A solution to this problem has been to balance tissue growth and hydrogel degradation. However, identifying this balance is difficult due to the complexity of coupling diffusion, deposition, and degradation mechanisms. Very little is known about the complex behavior of these mechanisms, emphasizing the need for a rigorous mathematical approach that can assist and guide experimental advances. To address this issue, this paper discusses a model for interstitial growth based on mixture theory, that can capture the coupling between cell mediated hydrogel degradation (i.e., hydrogels containing enzyme-sensitive crosslinks) and the transport of extracellular matrix (ECM) molecules released by encapsulated cells within a hydrogel. Taking cartilage tissue engineering as an example, the model investigates the role of enzymatic degradation on ECM diffusion and its impact on two important outcomes: the extent of ECM transport (and deposition) and the evolution of the hydrogel's mechanical integrity. Numerical results based on finite element analysis show that if properly tuned, enzymatic degradation yields the appearance of a highly localized degradation front propagating away from the cell, which can be immediately followed by a front of growing neotissue. We show that this situation is key to maintaining mechanical properties (e.g., stiffness) while allowing for deposition of new ECM molecules. Overall, our study suggests a hydrogel design that could enable successful tissue engineering (e.g., of cartilage, bone, etc.) where mechanical integrity is important. PMID- 27548745 TI - Genetic moderation of transactional relations between parenting practices and child self-regulation. AB - The present study addressed the ways in which parent and child dopamine D4 receptor (DRD4) genotypes jointly moderate the transactional relations between parenting practices and child self-regulation. African American children (N = 309) and their parents provided longitudinal data spanning child ages 11 to 15 years and a saliva sample from which variation at DRD4 was genotyped. Based on the differential susceptibility perspective, this study examined moderation effects of DRD4 status on (a) the extent to which parenting practices affect child self-regulation and (b) the extent to which child self-regulation, as an environmental influence on the parent, affects parenting behavior. Results indicated that responsive-supportive parenting interacted with children's DRD4 status to influence increases in child self-regulation. Also, child self regulation interacted with parent's DRD4 status to predict changes in parenting practices. Both Gene * Environment effects conformed to a differential susceptibility model in which parents' and children's DRD4 genes operated to increase environmental sensitivity "for better and for worse." (PsycINFO Database Record PMID- 27548746 TI - Mansoins C-F, Oligomeric Flavonoid Glucosides Isolated from Mansoa hirsuta Fruits with Potential Anti-inflammatory Activity. AB - Continued investigation of the polyphenolic pool of the fruits of Mansoa hirsuta afforded four additional members of the new class of glucosylated oligomeric flavonoids comprising a flavanone core linked to 1,3-diarylpropane C6-C3-C6 units. The structures and absolute configurations of mansoins C-F (3-6) were established by analysis of NMR and electronic circular dichroism data. Mansoin C (3) was identified as a diglucosylated heterodimer, whereas mansoins D (4), E (5), and F (6) were identified as triglucosylated heterotrimers, isomeric with mansoin A (1). Mansoin F (6) inhibited TNF-alpha release by lipopolysaccharide stimulated THP-1 cells (IC50 of 19.3 +/- 1.3 MUM) and, as with mansoin A (1), reduced the phosphorylation levels of p-65-NF-kappaB, when assayed at 50 MUM. These results indicate that the potential anti-inflammatory properties of mansoin F (6) are probably due to inhibition of the NF-kappaB pathway and inhibition of TNF-alpha release. PMID- 27548747 TI - Highly efficient gene tagging in the bryophyte Physcomitrella patens using the tobacco (Nicotiana tabacum) Tnt1 retrotransposon. AB - Because of its highly efficient homologous recombination, the moss Physcomitrella patens is a model organism particularly suited for reverse genetics, but this inherent characteristic limits forward genetic approaches. Here, we show that the tobacco (Nicotiana tabacum) retrotransposon Tnt1 efficiently transposes in P. patens, being the first retrotransposon from a vascular plant reported to transpose in a bryophyte. Tnt1 has a remarkable preference for insertion into genic regions, which makes it particularly suited for gene mutation. In order to stabilize Tnt1 insertions and make it easier to select for insertional mutants, we have developed a two-component system where a mini-Tnt1 with a retrotransposition selectable marker can only transpose when Tnt1 proteins are co expressed from a separate expression unit. We present a new tool with which to produce insertional mutants in P. patens in a rapid and straightforward manner that complements the existing molecular and genetic toolkit for this model species. PMID- 27548748 TI - Are we being drowned by overhydration advice on the Internet? AB - OBJECTIVE: Because inappropriate recommendations about hydration during exercise appear widespread and potentially dangerous, we assessed the quality of a sampling of information currently available to the public on the Internet. METHODS: Internet searches using the Google search engine were conducted using the terms "hydration," "hydration guidelines," "drinking fluids" and "drinking guidelines" combined with "and exercise." From the first 50 websites for each search phrase, duplicates were removed yielding 141 unique websites that were categorized by source and examined for specific hydration related information and recommendations. RESULTS: Correct endorsement was as follows (reported as percent endorsing the concept relative to the number of websites addressing the issue): some weight loss should be expected during exercise (69.5% of 95), fluid consumption during exercise should be based upon thirst (7.3% of 110), electrolyte intake is not generally necessary during exercise (10.4% of 106), dehydration is not generally a cause of heat illness (3.4% of 58) or exercise associated muscle cramping (2.4% of 42), exercise-associated muscle cramping is not generally related to electrolyte loss (0.0% of 16), and overhydration is a risk for hyponatremia (100.0% of 61). Comparison of website information from medical or scientific sources with that from other sources revealed no differences (p = 0.4 to 1.0) in the frequency of correct endorsement of the examined criteria. CONCLUSION: Prevalent misinformation on the Internet about hydration needs during exercise and the contribution of hydration status to the development of heat illness and muscle cramping fosters overhydration. In general, those websites that should be most trusted by the public were no better than other websites at providing accurate information, and the potential risk of hyponatremia from overhydration was noted by less than half the websites. Since deaths from exercise-associated hyponatremia should be preventable through avoidance of overhydration, dissemination of a more appropriate hydration message is important. PMID- 27548749 TI - Commentary on "A Tandem Cycling Program: Feasibility and Physical Performance Outcomes in People With Parkinson Disease". PMID- 27548750 TI - Relationship Between Walking Capacity, Biopsychosocial Factors, Self-efficacy, and Walking Activity in Persons Poststroke. AB - BACKGROUND/PURPOSE: Many factors appear to be related to physical activity after stroke, yet it is unclear how these factors interact and which ones might be the best predictors. Therefore, the purpose of this study was twofold: (1) to examine the relationship between walking capacity and walking activity, and (2) to investigate how biopsychosocial factors and self-efficacy relate to walking activity, above and beyond walking capacity impairment poststroke. METHODS: Individuals greater than 3 months poststroke (n = 55) completed the Yesavage Geriatric Depression Scale (GDS), Fatigue Severity Scale (FSS), Modified Cumulative Illness Rating (MCIR) Scale, Walk 12, Activities-Specific Balance Confidence (ABC) Scale, Functional Gait Assessment (FGA), and oxygen consumption testing. Walking activity data were collected via a StepWatch Activity Monitor. Predictors were grouped into 3 constructs: (1) walking capacity: oxygen consumption and FGA; (2) biopsychosocial: GDS, FSS, and MCIR; (3) self-efficacy: Walk 12 and ABC. Moderated sequential regression models were used to examine what factors best predicted walking activity. RESULTS: Walking capacity explained 35.9% (P < 0.001) of the variance in walking activity. Self-efficacy (DeltaR = 0.15, P < 0.001) and the interaction between the FGA*ABC (DeltaR = 0.047, P < 0.001) significantly increased the variability explained. The FGA (beta = 0.37, P = 0.01), MCIR (beta = -0.26, P = 0.01), and Walk 12 (beta = -0.45, P = 0.00) were each individually significantly associated with walking activity. DISCUSSION AND CONCLUSION: Although measures of walking capacity and self-efficacy significantly contributed to "real-world" walking activity, balance self-efficacy moderated the relationship between walking capacity and walking activity. Improving balance self-efficacy may augment walking capacity and translate to improved walking activity poststroke.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A139). PMID- 27548751 TI - Synthesis and Single-Molecule Conductances of Neutral and Cationic Indenofluorene Extended Tetrathiafulvalenes: Kondo Effect Molecules. AB - Development of molecules that can switch between redox states with paired and unpaired electrons is important for molecular electronics and spintronics. In this work, a selection of redox-active indenofluorene-extended tetrathiafulvalenes (IF-TTFs) with thioacetate end groups was prepared from a readily obtainable dibromo-functionalized IF-TTF building block using palladium catalyzed cross-coupling reactions, such as the Suzuki reaction. The end groups served as electrode anchoring groups for single-molecule conductance studies, and the molecules were subjected to mechanically controlled break-junction measurements with gold contacts and to low-bias charge transport measurements in gated three-terminal electromigration junctions. The neutral molecules showed clear conductance signatures, and somewhat surprisingly, we found that a meta meta anchoring configuration gave a higher conductance than a para-meta configuration. We explain this behavior by "through-space" coupling between the gold electrode and the phenyl on which the anchoring group is attached. Upon charging the molecule in a gated junction, we found reproducibly a Kondo effect (zero-bias conductance) attributed to a net spin. Ready generation of radical cations was supported by cyclic voltammetry measurements, revealing stepwise formation of radical cation and dication species in solution. The first oxidation event was accompanied by association reactions as the appearance of the first oxidation peak was strongly concentration dependent. PMID- 27548752 TI - HPV vaccine uptake in a school-located vaccination program. AB - Previous research has implied that while parents may be willing to have their adolescents receive some recommended vaccines via school-located vaccination program (SLVP), they were less likely to agree to the HPV vaccine being administered via SLVP. During an SLVP in a large urban area, 86% of those participating in the program received an HPV vaccine. PMID- 27548753 TI - Correlates of Strengthening Lessons from HIV/AIDS Treatment and Care Services in Ethiopia Perceived Access and Implications for Health System. AB - BACKGROUND: Access to healthcare is an important public health concept and has been traditionally measured by using population level parameters, such as availability, distribution and proximity of the health facilities in relation to the population. However, client based factors such as their expectations, experiences and perceptions which impact their evaluations of health care access were not well studied and integrated into health policy frameworks and implementation programs. OBJECTIVE: This study aimed to investigate factors associated with perceived access to HIV/AIDS Treatment and care services in Wolaita Zone, Ethiopia. METHODS: A cross-sectional survey was conducted on 492 people living with HIV, with 411 using ART and 81 using pre-ART services accessed at six public sector health facilities from November 2014 to March 2015. Data were analyzed using the ologit function of STATA. The variables explored consisted of socio-demographic and health characteristics, type of health facility, type of care, distance, waiting time, healthcare responsiveness, transportation convenience, satisfaction with service, quality of care, financial fairness, out of pocket expenses and HIV disclosure. RESULTS: Of the 492 participants, 294 (59.8%) were females and 198 (40.2%) were males, with a mean age of 38.8 years. 23.0% and 12.2% believed they had 'good' or 'very good' access respectively, and 64.8% indicated lower ratings. In the multivariate analysis, distance from the health facility, type of care, HIV clinical stage, out of pocket expenses, employment status, type of care, HIV disclosure and perceived transportation score were not associated with the perceived access (PA). With a unit increment in satisfaction, perceived quality of care, health system responsiveness, transportation convenience and perceived financial fairness scores, the odds of providing higher rating of PA increased by 29.0% (p<0.001), 6.0%(p<0.01), 100.0% (p<0.001), 9.0% (p<0.05) and 6.0% (p<0.05) respectively. CONCLUSION: Perceived quality of care, health system responsiveness, perceived financial fairness, transportation convenience and satisfaction with services were correlates of perceived access and affected healthcare performance. Interventions targeted at improving access to HIV/AIDS treatment and care services should address these factors. Further studies may be needed to confirm the findings. PMID- 27548754 TI - Expanding Synthesizable Space of Disubstituted 1,2,4-Oxadiazoles. AB - One-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and nitriles was optimized to parallel chemistry. The method was validated on a 141 member library; the desired products were recovered with a high success rate and in moderate yields. Practical application of the approach was demonstrated in the synthesis of bioactive compound pifexole and agonists of free fatty acid receptor 1. A library of 4 948 100 synthesizable drug-like 3,5-disubstituted 1,2,4-oxadiazoles was enumerated based on the method and available validated reagents. PMID- 27548755 TI - (15)N Heteronuclear Chemical Exchange Saturation Transfer MRI. AB - A two-step heteronuclear enhancement approach was combined with chemical exchange saturation transfer (CEST) to magnify (15)N MRI signal of molecules through indirect detection via water protons. Previous CEST studies have been limited to radiofrequency (rf) saturation transfer or excitation transfer employing protons. Here, the signal of (15)N is detected indirectly through the water signal by first inverting selectively protons that are scalar-coupled to (15)N in the urea molecule, followed by chemical exchange of the amide proton to bulk water. In addition to providing a small sensitivity enhancement, this approach can be used to monitor the exchange rates and thus the pH sensitivity of the participating (15)N-bound protons. PMID- 27548757 TI - Analgesic effect of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain. AB - The objective of the present study was to assess the benefits of 1-week repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain (LBP). The visual analogue scale (VAS), Short Form McGill pain questionnaire (SF-MPQ), and Short Form 36 Health Survey were used to evaluate the effect of this treatment. Eighty-two patients diagnosed with LBP were divided randomly into three groups: rTMS-treated group, sham group, and physical therapy treated group. We observed a significant reduction in VAS and SF-MPQ scores in the rTMS-treated group, but not in the sham group. Moreover, patients who received rTMS had a lower mean pain score than patients treated with physical therapy. Our study suggests that rTMS produces safe, significant, and long-term relief in patients with LBP without evident side effects. This study shows for the first time that long-term repeated sessions of rTMS decrease pain perception of LBP. Bioelectromagnetics. 37:527-535, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27548758 TI - Body Temperature Regulation in Hot Environments. AB - Organisms in hot environments will not be able to passively dissipate metabolically generated heat. Instead, they have to revert to evaporative cooling, a process that is energetically expensive and promotes excessive water loss. To alleviate these costs, birds in captivity let their body temperature increase, thereby entering a state of hyperthermia. Here we explore the use of hyperthermia in wild birds captured during the hot and dry season in central Nigeria. We found pronounced hyperthermia in several species with the highest body temperatures close to predicted lethal levels. Furthermore, birds let their body temperature increase in direct relation to ambient temperatures, increasing body temperature by 0.22 degrees C for each degree of increased ambient temperature. Thus to offset the costs of thermoregulation in ambient temperatures above the upper critical temperature, birds are willing to let their body temperatures increase by up to 5 degrees C above normal temperatures. This flexibility in body temperature may be an important mechanism for birds to adjust to predicted increasing ambient temperatures in the future. PMID- 27548756 TI - Longitudinal beta-Amyloid Deposition and Hippocampal Volume in Preclinical Alzheimer Disease and Suspected Non-Alzheimer Disease Pathophysiology. AB - Importance: Preclinical Alzheimer disease (AD) can be staged using a 2-factor model denoting the presence or absence of beta-amyloid (Abeta+/-) and neurodegeneration (ND+/-). The association of these stages with longitudinal biomarker outcomes is unknown. Objective: To examine whether longitudinal Abeta accumulation and hippocampal atrophy differ based on initial preclinical staging. Design, Setting, and Participants: This longitudinal population-based cohort study used data collected at the Knight Alzheimer Disease Research Center, Washington University, St Louis, Missouri, from December 1, 2006, to June 31, 2015. Cognitively normal older adults (n = 174) were recruited from the longitudinal Adult Children Study and Healthy Aging and Senile Dementia Study at the Knight Alzheimer Disease Research Center. At baseline, all participants had magnetic resonance imaging (MRI) scans, positron emission tomography (PET) scans with carbon 11-labeled Pittsburgh Compound B (PiB), and cerebrospinal fluid assays of tau and phosphorylated tau (ptau) acquired within 12 months. Using the baseline biomarkers, individuals were classified into preclinical stage 0 (Abeta /ND-), 1 (Abeta+/ND-), or 2+ (Abeta+/ND+) or suspected non-AD pathophysiology (SNAP; Abeta-/ND+). Main Outcomes and Measures: Subsequent longitudinal accumulation of Abeta assessed with PiB PET and loss of hippocampal volume assessed with MRI in each group. Results: Among the 174 participants (81 men [46.6%]; 93 women [53.4%]; mean [SD] age, 65.7 [8.9] years), a proportion (14% 17%) of individuals with neurodegeneration alone (SNAP) later demonstrated Abeta+. The rates of Abeta accumulation and loss of hippocampal volume in individuals with SNAP were indistinguishable from those without any pathologic features at baseline (for Abeta accumulation: when hippocampal volume was used to define ND, t = 0.00 [P > .99]; when tau and ptau were used to define ND, t = 0.02 [P = .98]; for loss of hippocampal volume: when hippocampal volume was used to define ND, t = -1.34 [P = .18]; when tau and ptau were used to define ND, t = 0.84 [P = .40]). Later preclinical stages (stages 1 and 2+) had elevated Abeta accumulation. Using hippocampal volume to define ND, individuals with stage 1 had accelerated Abeta accumulation relative to stage 0 (t = 11.06; P < .001), stage 2+ (t = 2.10; P = .04), and SNAP (t = 9.32; P < .001), and those with stage 2+ had accelerated Abeta accumulation relative to stage 0 (t = 4.38; P < .001) and SNAP (t = 4.08; P < .001). When ND was defined using tau and ptau, individuals with stage 2+ had accelerated Abeta accumulation relative to stage 0 (t = 4.96) and SNAP (t = 4.06), and those with stage 1 had accelerated Abeta accumulation relative to stage 0 (t = 8.44) and SNAP (t = 6.61) (P < .001 for all comparisons). When ND was defined using cerebrospinal fluid biomarkers, individuals with stage 2+ had accelerated hippocampal atrophy relative to stage 0 (t = -3.41; P < .001), stage 1 (t = -2.48; P = .03), and SNAP (t = -2.26; P = .03). Conclusions and Relevance: More advanced preclinical stages of AD have greater longitudinal Abeta accumulation. SNAP appears most likely to capture inherent individual variability in brain structure or to represent comorbid pathologic features rather than early emerging AD. Low hippocampal volumes or elevated levels of tau or ptau in isolation may not accurately represent ongoing neurodegenerative processes. PMID- 27548759 TI - Itch and systemic sclerosis: frequency, clinical characteristics and consequences. PMID- 27548760 TI - Predictors of benzodiazepine use among parents of children with cancer: a cross sectional study from Lebanon. PMID- 27548761 TI - An Ir/Zn Dual Catalysis for Enantio- and Diastereodivergent alpha-Allylation of alpha-Hydroxyketones. AB - An Ir/Zn dual catalysis has been developed for the enantio- and diastereodivergent alpha-allylation of unprotected alpha-hydroxyketones under mild conditions, in the absence of any additional base. The cooperative action of a chiral iridium complex derived from phosphoramidites and a chiral Zn-ProPhenol complex is most likely responsible for its high reactivity, excellent enantioselectivity (up to >99% ee), and good diastereoselectivity (up to >20:1 dr). All four product stereoisomers could be prepared from the same set of starting materials and under identical conditions by simple selection of appropriate catalyst combinations. PMID- 27548762 TI - Immersive Interprofessional Education Using an Evidence-Based Practice Course. AB - Beyond medical knowledge and clinical skills, physician assistant curricula must include instruction in collaborative, interprofessional, patient-centered, evidence-based practice (EBP). Development and implementation of interprofessional education (IPE) are challenging. This article describes a replicable model for an interprofessional graduate-level course that incorporates both exposure and immersion, allowing students to develop and demonstrate the Interprofessional Education Collaborative's 38 core competencies for interprofessional, collaborative decision making and problem solving while also acquiring functional skills in EBP. Pre- and postcourse surveys demonstrated both improved student self-confidence with EBP skills and appreciation for an interprofessional approach to patient care. Barriers to, and facilitators of, development and implementation of IPE courses, as well as effective IPE strategies and tools, are discussed. PMID- 27548763 TI - Hosting Global Visitors Seeking Information About the US Physician Assistant Career. PMID- 27548764 TI - Electronic Health Records: Practice for Competence in Clinical Environments. PMID- 27548765 TI - Expanding the Nanoarchitectural Diversity Through Aromatic Di- and Tri-Peptide Coassembly: Nanostructures and Molecular Mechanisms. AB - Molecular self-assembly is pivotal for the formation of ordered nanostructures, yet the structural diversity obtained by the use of a single type of building block is limited. Multicomponent coassembly, utilized to expand the architectural space, is principally based on empirical observations rather than rational design. Here we report large-scale molecular dynamics simulations of the coassembly of diphenylalanine (FF) and triphenylalanine (FFF) peptides at various mass ratios. Our simulations show that FF and FFF can co-organize into both canonical and noncanonical assemblies. Strikingly, toroid nanostructures, which were rarely observed for the extensively studied FF or FFF, are often seen in the FF-FFF coassembly simulations and later corroborated by scanning electron microscopy. Our simulations demonstrate a wide ratio-dependent variation of nanostructure morphologies including hollow and solid assemblies, much richer than those formed by each individual moiety. The hollow-solid structural transformation displays a discontinuous transition feature, and the toroids appear to be an obligatory intermediate for the structural transition. Interaction analysis reveals that the hollow-solid structural transition is mostly dominated by FF-FFF interactions, while the nanotoroid formation is determined by the competition between FF-water and FFF-water interactions. This study provides both structural and mechanistic insights into the coassembly of FF and FFF peptides, thus offering a molecular basis for the rational design of bionanomaterials utilizing peptide coassembly. PMID- 27548767 TI - Dominant-side onset in Parkinson's disease and better motor performance? PMID- 27548766 TI - Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial. AB - Importance: The efficacy of folic acid therapy on renal outcomes has not been previously investigated in populations without folic acid fortification. Objective: To test whether treatment with enalapril and folic acid is more effective in slowing renal function decline than enalapril alone across a spectrum of renal function at baseline from normal to moderate chronic kidney disease (CKD) among Chinese adults with hypertension. Design, Setting, and Participants: In this substudy of eligible China Stroke Primary Prevention Trial (CSPPT), 15 104 participants with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 or greater, including 1671 patients with CKD, were recruited from 20 communities in Jiangsu province in China. Interventions: Participants were randomized to receive a single tablet daily containing 10 mg enalapril and 0.8 mg folic acid (n = 7545) or 10 mg enalapril alone (n = 7559). Main Outcomes and Measures: The primary outcome was the progression of CKD, defined as a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73 m2 if the baseline eGFR was 60 mL/min/1.73 m2 or more, or a decrease in eGFR of 50% or more if the baseline eGFR was less than 60 mL/min/1.73 m2; or end-stage renal disease. Secondary outcomes included a composite of the primary outcome and all cause death, rapid decline in renal function, and rate of eGFR decline. Results: Overall, 15 104 Chinese adults with a mean (range) age of 60 (45-75) years were recruited; median follow-up was 4.4 years. There were 164 and 132 primary events in the enalapril group and the enalapril-folic acid group, respectively. Compared with the enalapril group, the enalapril-folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year; P = .02). Among the participants with CKD at baseline, folic acid therapy resulted in a significant reduction in the risks for the primary event (OR, 0.44; 95% CI, 0.26-0.75), rapid decline in renal function (OR, 0.67; 95% CI, 0.47-0.96) and the composite event (OR, 0.62; 95% CI, 0.43-0.90), and a 44% slower decline in renal function (0.96% vs 1.72% per year, P < .001). Among those without CKD at baseline, there was no between-group difference in the primary end point. Conclusions and Relevance: Enalapril-folic acid therapy, compared with enalapril alone, can significantly delay the progression of CKD among patients with mild-to-moderate CKD. Trial Registration: clinicaltrials.gov Identifier: NCT00794885. PMID- 27548768 TI - Survival and Growth of Listeria monocytogenes on Fresh-Cut "Athena" and "Rocky Ford" Cantaloupes During Storage at 4 degrees C and 10 degrees C. AB - Cantaloupes, marketed as "Rocky Ford," were implicated in the U.S. multistate outbreak of listeriosis in 2011, which caused multiple fatalities. Listeria monocytogenes can survive on whole cantaloupes and can be transferred to the flesh of melons. The growth of L. monocytogenes on fresh-cut "Athena" and "Rocky Ford" cantaloupe cultivars during refrigerated storage was evaluated. Fresh-cut cubes (16.4 cm3) from field-grown cantaloupes were each inoculated with 5 log10 CFU/mL of a multi-strain mixture of L. monocytogenes and stored at 4 degrees C or 10 degrees C. Inoculated fresh-cut cubes were also: (1) continuously stored at 4 degrees C for 3 days; (2) temperature-abused (TA: 25 degrees C for 4 h) on day 0; or (3) stored at 4 degrees C for 24 h, exposed to TA on day 1, and subsequently stored at 4 degrees C until day 3. L. monocytogenes populations on fresh-cut melons continuously stored at 4 degrees C or 10 degrees C were enumerated on selected days for up to 15 days and after each TA event. Brix values for each cantaloupe variety were determined. L. monocytogenes populations on fresh-cut cantaloupe cubes stored at 4 degrees C increased by 1.0 and 3.0 log10 CFU/cube by day 7 and 15, respectively, whereas those stored at 10 degrees C increased by 3.0 log10 CFU/cube by day 7. Populations of L. monocytogenes on fresh-cut cantaloupes stored at 10 degrees C were significantly (p < 0.05) greater than those stored at 4 degrees C during the study. L. monocytogenes showed similar growth on fresh-cut "Athena" and "Rocky Ford" cubes, even though "Athena" cubes had significantly higher Brix values than the "Rocky Ford" fruit. L. monocytogenes populations on fresh-cut cantaloupes exposed to TA on day 1 and then refrigerated were significantly greater (0.74 log10 CFU) than those stored continuously at 4 degrees C for 3 days. Storage at 10 degrees C or exposure to TA events promoted growth of L. monocytogenes on fresh-cut cantaloupe during refrigerated storage. PMID- 27548769 TI - Relationship of oscillating and average components of laser Doppler flowmetry signal. AB - Signals from laser Doppler flowmeters widely used in intravital studies of skin blood flow include, along with a slowly varying average component, an oscillating part. However, in most clinical studies, pulsations are usually smoothed by data preprocessing and only the mean blood flow is analyzed. To reveal the relationship between average and oscillating perfusion components measured by a laser Doppler flowmeter, we examined the microvascular response to the contralateral cold pressor test recorded at two different sites of the hand: dorsal part of the arm and finger pad. Such a protocol makes it possible to provide a wide range of perfusion. The average perfusion always decreases during cooling, while the oscillating component demonstrates a differently directed response. The wavelet analysis of laser Doppler flowmetry (LDF) signals shows that the pulsatile component is nonlinearly related to the average perfusion. Under low perfusion, the amplitude of pulsations is proportional to its mean value, but, as perfusion increases, the amplitude of pulsations becomes lower. The type of response is defined by the basal perfusion and the degree of vasoconstriction caused by cooling. Interpretation of the results is complicated by the nonlinear transfer function of the LDF device, the contribution of which is studied using artificial examples. PMID- 27548770 TI - Navigation of a robot-integrated fluorescence laparoscope in preoperative SPECT/CT and intraoperative freehand SPECT imaging data: a phantom study. AB - Robot-assisted laparoscopic surgery is becoming an established technique for prostatectomy and is increasingly being explored for other types of cancer. Linking intraoperative imaging techniques, such as fluorescence guidance, with the three-dimensional insights provided by preoperative imaging remains a challenge. Navigation technologies may provide a solution, especially when directly linked to both the robotic setup and the fluorescence laparoscope. We evaluated the feasibility of such a setup. Preoperative single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) or intraoperative freehand SPECT (fhSPECT) scans were used to navigate an optically tracked robot integrated fluorescence laparoscope via an augmented reality overlay in the laparoscopic video feed. The navigation accuracy was evaluated in soft tissue phantoms, followed by studies in a human-like torso phantom. Navigation accuracies found for SPECT/CT-based navigation were 2.25 mm (coronal) and 2.08 mm (sagittal). For fhSPECT-based navigation, these were 1.92 mm (coronal) and 2.83 mm (sagittal). All errors remained below the <1-cm detection limit for fluorescence imaging, allowing refinement of the navigation process using fluorescence findings. The phantom experiments performed suggest that SPECT-based navigation of the robot-integrated fluorescence laparoscope is feasible and may aid fluorescence-guided surgery procedures. PMID- 27548771 TI - Near-infrared indocyanine dye permits real-time characterization of both venous and lymphatic circulation. AB - We investigated the optical properties of a near-infrared (NIR) fluorochrome, di beta-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve. PMID- 27548772 TI - Combined photoacoustic, pulse-echo laser ultrasound, and speed-of-sound imaging using integrating optical detection. AB - A purely optical setup for the coregistration of photoacoustic (PA), ultrasound (US), and speed-of-sound (SOS) section images is presented. It extends a previously developed method for simultaneous PA and laser-US (LUS) pulse-echo imaging with a LUS transmission imaging setup providing two-dimensional (2-D) SOS maps. For transmission imaging, the sound waves traversing the investigated object are generated instantaneously by illuminating optically absorbing targets that are arranged at various distances in front of the sample. All signals are recorded by an optical beam which is part of a Mach-Zehnder interferometer that integrates the acoustic field along its path. Due to the cascaded arrangement of LUS sources, a single-recorded signal yields information for a projection of the SOS distribution. After collection of data from all directions, an inverse Radon transform is applied to this set of projections to obtain a 2-D SOS image. The setup is characterized and its performance is tested on phantom experiments. In addition to providing additional contrast, it is also shown that the resolution of the coregistered PA and LUS images can be improved by implementing the knowledge of the SOS distribution in the reconstruction. PMID- 27548773 TI - Experimental validation of tangential resolution improvement in photoacoustic tomography using modified delay-and-sum reconstruction algorithm. AB - For a circular scanning geometry in photoacoustic tomography, the axial/radial resolution is spatially invariant and is not affected by the ultrasound transducer (UST, detector) aperture. However, the tangential resolution is dependent on the detector aperture size and it varies spatially. Many techniques were proposed to improve the tangential resolution, such as attaching a concave lens in front of the nonfocused transducer or using a virtual point detector. Both of these methods have difficulties. Therefore, a modified delay-and-sum reconstruction algorithm has been proposed which can be used together with a standard ultrasound detector (nonfocused) to improve the tangential resolution. In this work, we validate the modified delay-and-sum algorithm experimentally for both flat and cylindrically focused USTs. More than threefold improvement in tangential resolution is observed. It is also shown that the object shape is recovered with this modified algorithm, which is very helpful for diagnosis and treatment purposes. PMID- 27548774 TI - Fiber Bragg grating sensor-based communication assistance device. AB - Improvements in emergency medicine in the form of efficient life supporting systems and intensive care have increased the survival rate in critically injured patients; however, in some cases, severe brain and spinal cord injuries can result in a locked-in syndrome or other forms of paralysis, and communication with these patients may become restricted or impossible. The present study proposes a noninvasive, real-time communication assistive methodology for those with restricted communication ability, employing a fiber Bragg grating (FBG) sensor. The communication assistive methodology comprises a breath pattern analyzer using an FBG sensor, which acquires the exhalation force that is converted into strain variations on a cantilever. The FBG breath pattern analyzer along with specific breath patterns, which are programmed to give specific audio output commands, constitutes the proposed fiber Bragg grating sensor-based communication assistive device. The basic communication can be carried out by instructing the patients with restricted communication ability to perform the specific breath patterns. The present approach is intended to be an alternative to the common approach of brain-computer interface in which an instrument is utilized for learning of brain responses. PMID- 27548775 TI - Aptamer-based fiber sensor for thrombin detection. AB - The detection of thrombin based on aptamer binding is studied using two different optical fiber-based configurations: long period gratings coated with a thin layer of titanium dioxide and surface plasmon resonance devices in optical fibers coated with a multilayer of gold and titanium dioxide. These structures are functionalized and the performance to detect thrombin in the range 10 to 100 nM is compared in transmission mode. The sensitivity to the surrounding refractive index (RI) of the plasmonic device is higher than 3100 nm RIU-1 in the RI range 1.335 to 1.355, a factor of 20 greater than the sensitivity of the coated grating. The detection of 10 nM of thrombin was accomplished with a wavelength shift of 3.5 nm and a resolution of 0.54 nM. PMID- 27548776 TI - Low-level laser therapy induces an upregulation of collagen gene expression during the initial process of bone healing: a microarray analysis. AB - This study investigates the histological modifications produced by low level laser therapy (LLLT) on the first day of bone repair, as well as evaluates the LLLT effects on collagen expression on the site of a fracture. Twenty Wistar rats were distributed into a control group (CG) and a laser group (LG). Laser irradiation of Ga-Al-As laser 830 nm, 30 mW, 94 s, 2.8 J was performed in five sessions. Animals were euthanized on day 5 postsurgery. Histopathological analysis showed that LLLT was able to increase deposition of granulation tissue and newly formed bone at the site of the injury. In addition, picrosirius analysis showed that collagen fiber organization in the LG was enhanced compared to CG. Microarray analysis demonstrated that LLLT produced an upregulation type I collagen (COL-I). Immunohistochemical analysis revealed that the subjects that were treated presented a higher immunoexpression of COL-I. Our findings indicated that LLLT improves bone healing by producing a significant increase in the expression of collagen genes. PMID- 27548777 TI - Beyond the Bedroom: Cognitive, Affective, and Behavioral Responses to Partner Touch in Women With and Without Sexual Problems. AB - Women with female sexual problems (FSP) are more likely than unaffected women to demonstrate negative appraisals, negative affect, and avoidance of sexual activity. Research suggests affected women also experience negative affect and avoidance in response to intimate partner contact for fear it will lead to sex. This online study examined whether women with FSP (N = 157) and without FSP (N = 129) exhibited different perceptions, affective reactions, and behavioral responses to hypothetical touch occurring outside sexual activity. Women (Mage = 30.70; SD = 6.66) were randomly assigned to one of three conditions representing hypothetical interactions with their partner (affectionate, sexual, or no touch), and answered questions about their perceptions of their partner's sexual intentions and their own anticipated negative affect and behavioral avoidance. Women with FSP reported higher perceptions of sexual intent, negative affect, and avoidance in the sexual touch condition, and higher negative affect in the affectionate touch condition, than women without FSP. Results highlight that women with FSP have more negative reactions to partners' hypothetical affectionate and sexual touch than women without FSP. Interventions for FSP may benefit from targeting women's perceptions, affective reactions, and behavioral reactions to partner touch when it occurs outside of explicitly sexual contexts. PMID- 27548778 TI - The European Board of Anaesthesiology recommendations for safe medication practice: First update. AB - These European Board of Anaesthesiology (EBA) recommendations for safe medication practice replace the first edition of the EBA recommendations published in 2011. They were updated because evidence from critical incident reporting systems continues to show that medication errors remain a major safety issue in anaesthesia, intensive care, emergency medicine and pain medicine, and there is an ongoing need for relevant up-to-date clinical guidance for practising anaesthesiologists. The recommendations are based on evidence wherever possible, with a focus on patient safety, and are primarily aimed at anaesthesiologists practising in Europe, although many will be applicable elsewhere. They emphasise the importance of correct labelling practice and the value of incident reporting so that lessons can be learned, risks reduced and a safety culture developed. PMID- 27548779 TI - Rapid Thermostabilization of Bacillus thuringiensis Serovar Konkukian 97-27 Dehydroshikimate Dehydratase through a Structure-Based Enzyme Design and Whole Cell Activity Assay. AB - Thermostabilization of an enzyme with complete retention of catalytic efficiency was demonstrated on recombinant 3-dehydroshikimate dehydratase (DHSase or wtAsbF) from Bacillus thuringiensis serovar konkukian 97-27 (hereafter, B. thuringiensis 97-27). The wtAsbF is relatively unstable at 37 degrees C, in vitro (t1/237 = 15 min), in the absence of divalent metal. We adopted a structure-based design to identify stabilizing mutations and created a combinatorial library based upon predicted mutations at specific locations on the enzyme surface. A diversified asbF library (~2000 variants) was expressed in E. coli harboring a green fluorescent protein (GFP) reporter system linked to the product of wtAsbF activity (3,4-dihydroxybenzoate, DHB). Mutations detrimental to DHSase function were rapidly eliminated using a high throughput fluorescence activated cell sorting (FACS) approach. After a single sorting round and heat screen at 50 degrees C, a triple AsbF mutant (Mut1), T61N, H135Y, and H257P, was isolated and characterized. The half-life of Mut1 at 37 degrees C was >10-fold higher than the wtAsbF (t1/237 = 169 min). Further, the second-order rate constants for both wtAsbF and Mut1 were approximately equal (9.9 * 105 M-1 s-1, 7.8 * 105 M-1 s-1, respectively), thus demonstrating protein thermostability did not come at the expense of enzyme thermophilicity. In addition, in vivo overexpression of Mut1 in E. coli resulted in a ~60-fold increase in functional enzyme when compared to the wild-type enzyme under the identical expression conditions. Finally, overexpression of the thermostable AsbF resulted in an approximate 80-120% increase in DHB accumulation in the media relative to the wild-type enzyme. PMID- 27548781 TI - Validity of the Jump-and-Reach Test in Subelite Adolescent Handball Players. AB - Muehlbauer, T, Pabst, J, Granacher, U, and Busch, D. Validity of the jump-and reach test in subelite adolescent handball players. J Strength Cond Res 31(5): 1282-1289, 2017-The primary purpose of this study was to examine concurrent validity of the jump-and-reach (JaR) test using the Vertec system and a criterion device (i.e., Optojump system). In separate subanalyses, we investigated the influence of gym floor condition and athletes' sex on the validity of vertical jump height. Four hundred forty subelite adolescent female (n = 222, mean age: 14 +/- 1 year, age range: 13-15 years) and male (n = 218, mean age: 15 +/- 1 year, age range: 14-16 years) handball players performed the JaR test in gyms with region or point elastic floors. Maximal vertical jump height was simultaneously assessed using the Vertec and the Optojump systems. In general, significantly higher jump heights were obtained for the Vertec compared with the Optojump system (11.2 cm, Delta31%, Cohen's d = 2.58). The subanalyses revealed significantly larger jump heights for the Vertec compared with the Optojump system irrespective of gym floor condition and players' sex. The association between Optojump- and Vertec-derived vertical jump heights amounted to rP = 0.84, with a coefficient of determination (R) of 0.71. The subanalyses indicated significantly larger correlations in males (rP = 0.75, R = 0.56) than in females (rP = 0.63, R = 0.40). Yet, correlations were not significantly different between region (rP = 0.83, R = 0.69) as opposed to point elastic floor (rP = 0.87, R = 0.76). Our findings indicate that the 2 apparatuses cannot be used interchangeably. Consequently, gym floor and sex-specific regression equations were provided to estimate true (Optojump system) vertical jump height from Vertec derived data. PMID- 27548780 TI - Cyclic Dipeptide Shuttles as a Novel Skin Penetration Enhancement Approach: Preliminary Evaluation with Diclofenac. AB - This study demonstrates the effectiveness of a peptide shuttle in delivering diclofenac into and through human epidermis. Diclofenac was conjugated to a novel phenylalanyl-N-methyl-naphthalenylalanine-derived diketopiperazine (DKP) shuttle and to TAT (a classical cell penetrating peptide), and topically applied to human epidermis in vitro. DKP and TAT effectively permeated into and through human epidermis. When conjugated to diclofenac, both DKP and TAT enhanced delivery into and through human epidermis, though DKP was significantly more effective. Penetration of diclofenac through human epidermis (to receptor) was increased by conjugation to the peptide shuttle and cell penetrating peptide with enhancement of 6x by DKP-diclofenac and 3x by TAT-diclofenac. In addition, the amount of diclofenac retained within the epidermis was significantly increased by peptide conjugation. COX-2 inhibition activity of diclofenac was retained when conjugated to DKP. Our study suggests that the peptide shuttle approach may offer a new strategy for targeted delivery of small therapeutic and diagnostic molecules to the skin. PMID- 27548782 TI - Reliability of Triaxial Accelerometry for Measuring Load in Men's Collegiate Ice Hockey. AB - Van Iterson, EH, Fitzgerald, JS, Dietz, CC, Snyder, EM, and Peterson, BJ. Reliability of triaxial accelerometry for measuring load in men's collegiate ice hockey. J Strength Cond Res 31(5): 1305-1312, 2017-Wearable microsensor technology incorporating triaxial accelerometry is used to quantify an index of mechanical stress associated with sport-specific movements termed PlayerLoad. The test-retest reliability of PlayerLoad in the environmental setting of ice hockey is unknown. The primary aim of this study was to quantify the test-retest reliability of PlayerLoad in ice hockey players during performance of tasks simulating game conditions. Division I collegiate male ice hockey players (N = 8) wore Catapult Optimeye S5 monitors during repeat performance of 9 ice hockey tasks simulating game conditions. Ordered ice hockey tasks during repeated bouts included acceleration (forward or backward), 60% top-speed, top-speed (forward or backward), repeated shift circuit, ice coasting, slap shot, and bench sitting. Coefficient of variation (CV), intraclass correlation coefficient (ICC), and minimum difference (MD) were used to assess PlayerLoad reliability. Test-retest CVs and ICCs of PlayerLoad were as follows: 8.6% and 0.54 for forward acceleration, 13.8% and 0.78 for backward acceleration, 2.2% and 0.96 for 60% top speed, 7.5% and 0.79 for forward top-speed, 2.8% and 0.96 for backward top-speed, 26.6% and 0.95 for repeated shift test, 3.9% and 0.68 for slap shot, 3.7% and 0.98 for coasting, and 4.1% and 0.98 for bench sitting, respectively. Raw differences between bouts were not significant for ice hockey tasks (p > 0.05). For each task, between-bout raw differences were lower vs. MD: 0.06 vs. 0.35 (forward acceleration), 0.07 vs. 0.36 (backward acceleration), 0.00 vs. 0.06 (60% top-speed), 0.03 vs. 0.20 (forward top-speed), 0.02 vs. 0.09 (backward top speed), 0.18 vs. 0.64 (repeated shift test), 0.02 vs. 0.10 (slap shot), 0.00 vs. 0.10 (coasting), and 0.01 vs. 0.11 (bench sitting), respectively. These data suggest that PlayerLoad demonstrates moderate-to-large test-retest reliability in the environmental setting of male Division I collegiate ice hockey. Without previously testing reliability, these data are important as PlayerLoad is routinely quantified in male collegiate ice hockey to assess on ice physical activity. PMID- 27548784 TI - Acute Kinematic and Kinetic Adaptations to Wearable Resistance During Sprint Acceleration. AB - Macadam, P, Simperingham, KD, and Cronin, JB. Acute kinematic and kinetic adaptations to wearable resistance during sprint acceleration. J Strength Cond Res 31(5): 1297-1304, 2017-Wearable resistance (WR) in the form of weighted vests and shorts enables movement-specific sprint running to be performed under load. The purpose of this study was to determine the acute changes in kinematics and kinetics when an additional load equivalent to 3% body mass (BM) was attached to the anterior or posterior surface of the lower limbs during sprint running. Nineteen male rugby athletes (age: 19.7 +/- 2.3 years; body mass: 96.1 +/- 16.5 kg; height: 181 +/- 6.5 cm) volunteered to participate in the study. Subjects performed six 20 m sprints in a randomized fashion wearing no resistance or 3%BM affixed to the anterior (quadriceps and tibialis anterior) or posterior (hamstring and gastrocnemius) surface of the lower limbs (2 sprints per condition). Optojump and radar were used to quantify sprint times, horizontal velocity, contact and flight times, and step length and frequency. A repeated measures analysis of variance with post hoc contrasts was used to determine differences (p <= 0.05) between conditions. No significant differences were found between the anterior and posterior WR conditions in any of the variables of interest. There was no significant change in sprint times over the initial 10 m, however, the 10-20 m split times were significantly slower (-2.2 to -2.9%) for the WR conditions compared with the unloaded sprints. A significant change in the relative force-velocity (F-v) slope (-10.5 to -10.9%) and theoretical maximum velocity (V0) (-5.4 to -6.5%) was found, whereas a nonsignificant increase in theoretical maximum force (F0) (4.9-5.2%) occurred. Wearable resistance of 3%BM may be a suitable training modality to enhance sprint acceleration performance by overloading the athlete without negatively affecting sprint running technique. PMID- 27548785 TI - Sex and Weight Category Differences in Time-Motion Analysis of Elite Judo Athletes: Implications for Assessment and Training. AB - Sterkowicz-Przybycien, K, Miarka, B, and Fukuda, DH. Sex and weight category differences in time-motion analysis of elite judo athletes: implications for assessment and training. J Strength Cond Res 31(3): 817-825, 2017-The purpose of this investigation was to support training program development through the comparison of combat and pause phases during elite male and female judo competition in athletes of varying weight categories. A total of 1,411 video recorded judo matches between athletes who qualified for the 2012 Olympic Games were analyzed. Within the matches, 111,203 competitive situations were categorized as combat (with subphases of approach, gripping, attack, defense, and groundwork) or pause phases. Time-motion analysis data were compared between extra light, light, middle, and heavyweight categories for men and women. Median times varied between sex and weight category groups for individual combat (23.9 28.5 seconds), pause (4.0-8.8 seconds), and combat subphases (p <= 0.05). Sex based differences in accumulated combat and combat subphase times were primarily found in the middleweight athletes. Heavyweight female athletes had longer accumulated groundwork and pause times, extra lightweight women had greater groundwork time, and both extra light and lightweight women had shorter accumulated attack times compared with their male counterparts. No differences between men and women were found for the time to complete an individual combat action; however, the pause phase and most of the combat subphases displayed differences. The lightest and heaviest judo athletes displayed unique characteristics compared with athletes in the other weight categories, particularly in the attack, defense, groundwork, and pause phases. These results have important implications related to training program design and support the need for the development of normative data for male and female judo athletes of varying weight categories. PMID- 27548786 TI - Hydration Status, Executive Function, and Response to Orthostatism After a 118-km Mountain Race: Are They Interrelated? AB - Martinez-Navarro, I, Chiva-Bartoll, O, Hernando, B, Collado, E, Porcar, V, and Hernando, C. Hydration status, executive function and response to orthostatism after a 118-km mountain race: are they interrelated? J Strength Cond Res 32(2): 441-449, 2018-The present study aimed to explore whether blood pressure (BP) and heart rate (HR) variability (HRV) responsiveness to orthostatism, jointly with executive function (EF) performance, was diminished after an ultra-endurance mountain race. Besides, we wanted to assess whether hydration status was related to either performance or the abovementioned alterations. Fifty recreational ultra endurance athletes participating in the Penyagolosa Trails CSP115 race (118 km and a total positive elevation of 5,439 m) were evaluated before and after the competition. The HRV and BP were measured in response to an orthostatic challenge. The EF was evaluated using the color-word interference task of the Stroop test. Body mass (BM) and urine specific gravity (USG) changes were used to assess hydration status. The HRV and BP responsiveness to orthostatism was diminished after the race. Besides, a significant BM loss of 3.51 +/- 2.03% was recorded. Conversely, EF and USG showed no significant changes from prerace to postrace. Eventually, BM loss was inversely related to finishing time (r = -0.34) and postrace orthostatic HR and EF were positively associated (r = 0.60). The USG and BM loss appear to provide different insights into hydration status, and our results challenge the well-established criteria that BM losses >2% are detrimental to performance. Coaches are advised to consider athletes' performance level when interpreting their BM changes during an ultra-endurance competition. Similarly, coaches should be aware that increased vulnerability to orthostatism is a common phenomenon after ultra-endurance races, and diminished HR responsiveness to orthostatism could constitute a practical indicator of EF worsening. PMID- 27548787 TI - High-Intensity Interval Cycling Exercise on Wave Reflection and Pulse Wave Velocity. AB - Kingsley, JD, Tai, YL, Vaughan, J, and Mayo, X. High-intensity interval cycling exercise on wave reflection and pulse wave velocity. J Strength Cond Res 31(5): 1313-1320, 2017-The purpose of this study was to assess the effects of high intensity exercise on wave reflection and aortic stiffness. Nine young, healthy men (mean +/- SD: age: 22 +/- 2 years) participated in the study. The high intensity interval cycling exercise consisted of 3 sets of Wingate Anaerobic Tests (WATs) with 7.5% of bodyweight as resistance and 2 minutes of rest between each set. Measurements were taken at rest and 1 minute after completion of the WATs. Brachial and aortic blood pressures, as well as wave reflection characteristics, were measured through pulse wave analysis. Aortic stiffness was assessed through carotid-femoral pulse wave velocity (cfPWV). A repeated-measures analysis of variance was used to investigate the effects of the WATs on blood pressure and vascular function across time. There was no change in brachial or aortic systolic pressure from rest to recovery. There was a significant (p <= 0.05) decrease in brachial diastolic pressure (rest: 73 +/- 6 mm Hg; recovery: 67 +/- 9 mm Hg) and aortic diastolic pressure (rest: 75 +/- 6 mm Hg; recovery: 70 +/ 9 mm Hg) from rest to recovery. In addition, there was no significant change in the augmentation index (rest: 111.4 +/- 6.5%; recovery: 109.8 +/- 5.8%, p = 0.65) from rest to recovery. However, there was a significant (p <= 0.05) increase in the augmentation index normalized at 75 b.min (rest: 3.29 +/- 9.82; recovery 21.21 +/- 10.87) during recovery compared with rest. There was no change in cfPWV (rest: 5.3 +/- 0.8 m.s; recovery: 5.7 +/- 0.5m.s; p = 0.09) in response to the WAT. These data demonstrate that high-intensity interval cycling exercise with short rest periods has a nonsignificant effect on vascular function. PMID- 27548791 TI - A 2-Month Linear Periodized Resistance Exercise Training Improved Musculoskeletal Fitness and Specific Conditioning of Navy Cadets. AB - Vantarakis, A, Chatzinikolaou, A, Avloniti, A, Vezos, N, Douroudos, II, Draganidis, D, Jamurtas, AZeta, Kambas, A, Kalligeros, S, and Fatouros, IG. A 2 month linear periodized resistance exercise training improved musculoskeletal fitness and specific conditioning of navy cadets. J Strength Cond Res 31(5): 1362 1370, 2017-Major objectives of army and navy training are the development of readiness, performance, and injury prevention. Numerous studies have examined the effect of specific strength training (ST) programs on performance of Special Forces and military personnel. Although navy personnel have to address on-board conditions that require the development of strength, agility, speed, and task specific endurance, there is no information regarding the effects of ST on navy specific performance. Therefore, the purpose of this study was to investigate the effect of an 8-week ST on performance of navy cadets. Thirty-one cadets of the Hellenic Naval Academy volunteered to participate and were randomly assigned in 2 groups. Cadets in the Experimental Group participated in a linear periodized ST program in addition to their daily training schedule. Cadets in the control group participated only in pre- and post-measurements. Anthropometrics, maximal oxygen consumption, oxygen consumption during a Navy Obstacle Course (NOC), maximum strength in bench press and squat exercises, hand grip strength, repetitions in push-ups and abdominal test, time to complete a 30-m sprint, and time to complete NOC were measured before and after the intervention. A 2-way repeated-measures analysis of variance showed that ST induced favorable changes in bench press and squat 1 repetition maximum, push-ups, abdominal crunches, time to complete 30-m distance, and time to complete the NOC. These results indicate that an additional ST may induce positive alterations on readiness and performance of navy cadets. The study has the approval of university's institutional review board and ethical committee. PMID- 27548792 TI - Physical Demands of Representative Match-Play in Adolescent Rugby Union. AB - Read, DB, Jones, B, Phibbs, PJ, Roe, GAB, Darrall-Jones, J, Weakley, JJS, and Till, K. Physical demands of representative match-play in adolescent rugby union. J Strength Cond Res 31(5): 1290-1296, 2017-The purpose of this study was to quantify the physical demands of representative adolescent rugby union match-play and investigate the difference between playing positions and age groups. Players (n = 112) were classified into 6 groups by playing position (forwards and backs) and age group (U16, U18, and U20). The physical demands were measured using microsensor-based technology and analyzed using magnitude-based inferences to assess practical importance. Backs had a greater relative distance (except U16s) and a greater high-speed running distance per minute than forwards, with the magnitude of difference between the positions becoming larger in older age groups. Forwards had higher values of PlayerLoad (PL) per minute (accumulated accelerations from the 3 axes of movement) and PL slow per minute (accumulated accelerations from the 3 axes of movement where velocity is <2 m.s) than backs at all age groups. Relative distance, low-, and high-speed running per minute all had a trend to be lower in older age groups for both positions. PlayerLoad per minute was greater in U18 than that in U16 and U20 for both positions. PlayerLoad slow per minute was greater for older age groups besides the U18 and U20 comparisons, which were unclear. The contrasts in physical demands experienced by different positions reinforce the need for greater exposure to sprinting and collision-based activity for backs and forwards, respectively. Given PL metrics peak at U18 and locomotor demands seem to be lower in older ages, the demands of representative adolescent rugby union do not seem to be greater at U20 as expected. PMID- 27548794 TI - The Effects of Caffeine on Arousal, Response Time, Accuracy, and Performance in Division I Collegiate Fencers. AB - Doyle, TP, Lutz, RS, Pellegrino, JK, Sanders, DJ, and Arent, SM. The effects of caffeine on arousal, response time, accuracy, and performance in Division I collegiate fencers. J Strength Cond Res 30(11): 3228-3235, 2016-Caffeine has displayed ergogenic effects on aerobic performance. However, sports requiring precision and quick reaction may also be impacted by central nervous system arousal because of caffeine consumption. The purpose of this study was to assess the effects of caffeine on arousal, response time (RT), and accuracy during a simulated fencing practice. Using a randomized, within-subjects, placebo controlled, double-blind design, Division I male and female college fencers (N = 13; 69.1 +/- 3.5 kg) were administered caffeine doses of 0, 1.5, 3.0, 4.5, 6.0, or 7.5 mg.kg during separate testing days. Performance was assessed via RT and accuracy to a 4-choice reaction task. A total of 25 trials were performed each day using a random 2- to 8-s delay between trials. Arousal was assessed using the activation-deactivation adjective check list. Results of repeated-measures multivariate analysis of variance revealed a significant dose effect (p = 0.02) on performance. Follow-up analyses indicated this was due to a significant effect for RT (p = 0.03), with the dose-response curve exhibiting a quadratic relationship. Response time was significantly faster (p < 0.01) for the 1.5, 3.0, and 6.0 mg.kg conditions than for the placebo condition. Results also indicated a significant dose effect for composite RT + accuracy performance (p < 0.01). The dose-response curve was again quadratic, with performance beginning to deteriorate at 7.5 mg.kg. Energetic arousal, tiredness, tension, and calmness all significantly changed as a function of caffeine dose (p <= 0.05). Based on these results, caffeine improves RT and overall performance in fencers, particularly as doses increase up to 4.5-6.0 mg.kg. Above this level, performance begins to deteriorate, consistent with an "inverted-U" model of arousal and performance. PMID- 27548797 TI - Isometric Midthigh Pull Reliability and Relationship to Deadlift One Repetition Maximum. AB - De Witt, JK, English, KL, Crowell, JB, Kalogera, KL, Guilliams, ME, Nieschwitz, BE, Hanson, AM, and Ploutz-Snyder, LL. Isometric midthigh pull reliability and relationship to deadlift one repetition maximum. J Strength Cond Res 32(2): 528 533, 2018-The purpose of this investigation was to examine the reliability of the isometric midthigh pull (IMTP) and the relationship between IMTP peak force and deadlift 1 repetition maximum (1RM). Nine subjects (5 men and 4 women; 40.6 +/- 8.0 years; 1.72 +/- 0.10 m; 75.6 +/- 13.4 kg) participated in this study. Isometric midthigh pull and deadlift 1RM were both performed during 2 testing sessions. For IMTP, peak force and peak rate of force development (RFD) were determined, in addition to RFD at 30 ms, 50 ms, 90 ms, 150 ms, 200 ms, and 250 ms after initiation of the pull. Intraclass correlation coefficients (ICCs) were calculated to evaluate the reliability of IMTP measures. Pearson product-moment correlations and linear regression were used to determine associations between IMTP and deadlift 1RM. Isometric midthigh pull peak force was reproducible both within (ICC = 0.98 and 0.97) and between sessions (ICC = 0.89) and significantly correlated with deadlift 1RM (r = 0.88, p <= 0.05), but intermediate force outputs and RFD were not. Lack of associations between RFD and deadlift 1RM indicate that the ability to create explosive force may be independent of the ability to create maximal force. The strong relationship between IMTP peak force and deadlift 1RM was present regardless of which IMTP repetition across the 2 sessions was examined. Peak force generated during IMTP is a reliable method to assess full body maximal strength. A single IMTP repetition, provided adequate familiarization and warm-up, correlates strongly with deadlift 1RM. Practitioners can use the IMTP test as a method to estimate maximal deadlift strength in a quick and potentially less provocative manner than traditional 1RM testing. PMID- 27548798 TI - Acute Effects of Static vs. Ballistic Stretching on Strength and Muscular Fatigue Between Ballet Dancers and Resistance-Trained Women. AB - Lima, CD, Brown, LE, Wong, MA, Leyva, WD, Pinto, RS, Cadore, EL, and Ruas, CV. Acute effects of static vs. ballistic stretching on strength and muscular fatigue between ballet dancers and resistance-trained women. J Strength Cond Res 30(11): 3220-3227, 2016-Stretching is used to increase joint range of motion, but the acute effects can decrease muscle strength. However, this may depend on the population or mode of stretching. The purpose of this study was to compare the acute effects of static vs. ballistic stretching on strength and muscular fatigue between ballet dancers and resistance-trained women. Fifteen resistance-trained women (age 23.8 +/- 1.80 years, mass 67.47 +/- 7.77 kg, height 168.30 +/- 5.53 cm) and 12 ballet dancers (age 22.8 +/- 3.04 years, mass 58.67 +/- 5.65 kg, height 168.00 +/- 7.69 cm) performed 5 days of testing. The first day was control (no stretching), whereas the other 4 days were static or ballistic stretching in a counterbalanced order. Range of motion, strength, and fatigue tests were also performed. Both groups demonstrated a significant decrease in hamstrings strength after static (102.71 +/- 2.67 N.m) and ballistic stretching (99.49 +/- 2.61 N.m) compared with control (113.059 +/- 3.25 N.m), with no changes in quadriceps strength. For fatigue, only ballet dancers demonstrated a decrease from control (71.79 +/- 4.88%) to ballistic (65.65 +/- 8.19%), but no difference with static (65.01 +/- 12.29%). These findings suggest that stretching decreases hamstrings strength similarly in ballet dancers and resistance-trained women, with no differences between modes of stretching. However, ballistic stretching only decreased muscular fatigue in ballet dancers, but not in resistance-trained women. Therefore, no stretching should be performed before strength performance. However, ballistic stretching may decrease acute muscular fatigue in ballet dancers. PMID- 27548799 TI - Nonlinear Analysis of an Unstable Bench Press Bar Path and Muscle Activation. AB - Lawrence, MA, Leib, DJ, Ostrowski, SJ, and Carlson, LA. Nonlinear analysis of an unstable bench press bar path and muscle activation. J Strength Cond Res 31(5): 1206-1211, 2017-Unstable resistance exercises are typically performed to improve the ability of stabilizing muscles to maintain joint integrity under a load. The purpose of this study was to examine the effects of an unstable load (as provided by a flexible barbell and a load suspended by elastic bands) on the bar path, the primary musculature, and stabilizing musculature while bench pressing using nonlinear analyses. Fifteen resistance-trained men (age 24.2 +/- 2.7 years, mass 84.1 +/- 12.0 kg, height 1.77 +/- 0.05 m, 9.9 +/- 3.4 years of lifting experience, and bench press 1 repetition maximum (RM) 107.5 +/- 25.9 kg) volunteered for this study. Subjects pressed 2 sets of 5 repetitions in both stable (total load 75% 1RM) and unstable (total load 60% 1RM) conditions using a standard barbell and a flexible Earthquake bar, respectively. Surface electromyography was used to detect muscle activity of primary movers (pectoralis major, anterior deltoid, and triceps) and bar stabilizing musculature (latissimus dorsi, middle and posterior deltoid, biceps brachii, and upper trapezius). During the unstable condition, the bar moved in more ways and was less predictable in the mediolateral and anteroposterior directions. However, the muscle activation patterns of all muscles were more constrained with the unstable barbell. These findings suggest that the unstable condition was more challenging to control, but subjects controlled the instability by contracting their muscles in a more stable pattern or "staying tight" throughout the exercise. PMID- 27548800 TI - The Effect of Glycation on Epidermal Lipid Content, Its Metabolism and Change in Barrier Function. AB - BACKGROUND/AIMS: Advanced glycation end products, which are linked to both aging and hyperglycemia, cause marked functional and structural alterations in human skin. Though it is well known that the metabolism of glucose is closely associated with that of fatty acid (FA), sharing the same energy-yielding reaction pathways as glucose, its effect on the epidermis has been unclear so far. METHODS: Content of ceramides, cholesterol and FA in a reconstructed epidermal model glycated by glyoxal was analyzed by high-performance thin-layer chromatography. FA species extracted from HaCaT keratinocytes was determined by gas chromatography/mass spectrometry. Regulation of FA synthesis was analyzed by real-time PCR. For physiological analysis, excised mouse skin was glycated using a vertical diffusion cell and used for the evaluation of barrier function by transepidermal water loss measurement and observation of penetration of sodium fluorescein. RESULTS: Saturated FA content was significantly increased in glycated epidermis, and glycation upregulated mRNA expression of FA elongases 2 and 3 and FA synthase in HaCaT cells. Further, both inside-out and outside-in barriers were disrupted in glycated excised skin. CONCLUSION: Biological and physical change in the epidermis, especially upregulation of FA synthesis by glycation, contributed to barrier disruption, and inhibiting glycation may offer an effective treatment option for aged or glycated skin. PMID- 27548801 TI - Non-prescription sale and dispensing of antibiotics in community pharmacies in Zambia. AB - BACKGROUND: In Zambia, antibiotics are categorized as prescription-only medicines. Antibiotics dispensed without a prescription pose a public health threat, which is a concern. Consequently, the aim is to ascertain the extent of non-prescription sales and dispensing of antibiotics in community pharmacies in Zambia. METHODS: The practice of non-prescription sale and dispensing were assessed in 73 randomly selected community retail pharmacies, using a structured interviewer-administered questionnaire with simulated case scenarios. RESULTS: Majority (97%) stated that clients frequently requested non-prescribed antibiotics. Interviewees usually asked clients' indications (94%), counselled on dosing (96%) and suggested changes to antibiotic choices (97%). All (100%) dispensed non-prescribed antibiotics. Commonly dispensed antibiotics included amoxicillin (52%), cotrimoxazole (25%) and metronidazole (23%). Non-prescription sale and dispensing of antibiotics was significantly associated with interviewees' professional qualification in four out of five simulations. CONCLUSION: Non-prescription sale and dispensing of antibiotics is widespread in Zambia. Concerted public and professional interventions are needed coupled with stronger regulatory enforcement to reduce this. PMID- 27548802 TI - A melanin-bleaching methodology for molecular and histopathological analysis of formalin-fixed paraffin-embedded tissue. AB - Removal of excessive melanin from heavily pigmented formalin-fixed paraffin embedded (FFPE) melanoma tissues is essential for histomorphological and molecular diagnostic assessments. Although there have been efforts to address this issue, current methodologies remain complex and time-consuming, and are not suitable for multiple molecular applications. Herein, we have developed a robust and rapid melanin-bleaching methodology for FFPE tissue specimens. Our approach is based on quick bleaching (15 min) at high temperature (80 degrees C) with 0.5% diluted hydrogen peroxide (H2O2) in Tris-HCl, PBS, or Tris/Tricine/SDS buffer. Immunostaining for Ki-67 and HMB45 was enhanced by bleaching with 0.5% H2O2 in Tris/Tricine/SDS and Tris-HCl, respectively. In addition to histopathological applications, our approach also facilitates recovery of protein and nucleic acid from archival melanin-rich FFPE tissue sections. Protein extracted from bleached FFPE tissues was compatible with western blotting using anti-human GAPDH and AKT antibodies. Our bleaching condition significantly improved RNA quality compared with unbleached tissues without compromising the yield. Notably, the RNA/DNA obtained from bleached tissues was suitable for end point PCR and real-time quantitative RT-PCR. In conclusion, this improved melanin bleaching method enhances and simplifies immunostaining procedures, and facilitates the use of melanin-rich FFPE tissues for histomorphological and PCR amplification-based molecular assays. PMID- 27548803 TI - Isolation and characterization of hepatic mast cells from cholestatic rats. AB - Mast cells (MCs) are immune cells that release histamine and other mediators. MC number increases after bile duct ligation (BDL) and blocking mast cell-derived histamine decreases biliary proliferation. We aimed to isolate and characterize MCs from cholestatic livers. Rats were subjected to BDL starting at 6 h and up to 14 days. MC infiltration was evaluated by toluidine blue. BDL rats were perfused using standard collagenase perfusion. Following enzymatic digestion, tissue was passed through a fine gauge needle. Suspensions were incubated with MAb AA4, washed and incubated with goat anti-mouse-coated Dynal beads. MCs were stained with toluidine blue, and in isolated MCs the expression of FCERI and MC proteases was measured. The expression of histidine decarboxylase, histamine receptors, VEGF receptors, and TIE 1 and 2 was evaluated by qPCR. Histamine and VEGF-A secretion was measured in MC supernatants. MC purity was evaluated by CK-19, CK 8, albumin, VAP-1, and alpha-SMA expression. In vitro, cholangiocytes and HSCs were treated with isolated MC supernatants from BDL rats treated with either NaCl or cromolyn sodium (to block MC histamine release) and biliary proliferation and hepatic fibrosis were measured. MCs infiltrate the liver and surround bile ducts starting at day 2. We isolated a virtually pure preparation of mature, functional MCs. TEM images reveal distinct secretory granules and isolated MCs secrete histamine. MCs express FCERI, chymase, tryptase, RMCP-I, and RMCP-II, but were virtually void of other cell markers. Biliary proliferation and fibrosis increased following treatment with MC supernatants from BDL rats+NaCl and these parameters decreased in cells treated with MC supernatants from BDL+cromolyn sodium. In conclusion, we have isolated and characterized MCs from cholestatic livers. MCs regulate cholestatic liver injury and hepatic fibrosis. This tool provides a better understanding of the paracrine influence of mast cells on biliary/liver pathologies. PMID- 27548804 TI - The effect of fluoride on the structure, function, and proteome of a renal epithelial cell monolayer. AB - High concentrations of fluoride in the body may cause toxic effects. Here, we investigated the effects of fluoride on the structure, function, and proteome of a cortical collecting duct epithelium in vitro. Kidney tubule cells (M-1) were chosen because the concentration of fluoride in the kidney is 4-5-fold higher than that in plasma. Mouse M-1 cell monolayers were incubated in fluoride containing media, and the amiloride-sensitive short-circuit current and transepithelial resistance were measured. The Young's modulus of the epithelium was determined using atomic force microscopy, and the effect of fluoride on epithelial structure was assessed using scanning and transmission electron microscopy, and immunofluorescence. Differences in the expression of membrane proteins were evaluated using proteomics and bioinformatics. Fluoride exposure reduced both transepithelial Na+ transport and resistance. The IC50 for fluoride was ~300 uM for both effects, and the half-times for the decays of ion transport and resistance were 8.4 h and 3.6 days, respectively. Fluoride treatment did not affect the sensitivity of Na+ transport to amiloride. The Young's modulus of the epithelium was also unaffected by fluoride; however, the functional effects of fluoride were accompanied by marked structural effects. Proteomic analysis revealed changes in expression of a number of proteins, and particularly mitochondrial proteins. Treatment with fluoride had profound effects on the structure, function and proteome of a model cortical collecting duct epithelium. Significantly, however, these effects were produced only at concentrations considerably higher than those likely to be encountered in vivo. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1455-1467, 2017. PMID- 27548805 TI - Comparing diagnostic tests on benefit-risk. AB - Comparing diagnostic tests on accuracy alone can be inconclusive. For example, a test may have better sensitivity than another test yet worse specificity. Comparing tests on benefit risk may be more conclusive because clinical consequences of diagnostic error are considered. For benefit-risk evaluation, we propose diagnostic yield, the expected distribution of subjects with true positive, false positive, true negative, and false negative test results in a hypothetical population. We construct a table of diagnostic yield that includes the number of false positive subjects experiencing adverse consequences from unnecessary work-up. We then develop a decision theory for evaluating tests. The theory provides additional interpretation to quantities in the diagnostic yield table. It also indicates that the expected utility of a test relative to a perfect test is a weighted accuracy measure, the average of sensitivity and specificity weighted for prevalence and relative importance of false positive and false negative testing errors, also interpretable as the cost-benefit ratio of treating non-diseased and diseased subjects. We propose plots of diagnostic yield, weighted accuracy, and relative net benefit of tests as functions of prevalence or cost-benefit ratio. Concepts are illustrated with hypothetical screening tests for colorectal cancer with test positive subjects being referred to colonoscopy. PMID- 27548806 TI - The Kaiser Permanente Northern California Adult Member Health Survey. AB - INTRODUCTION: The Kaiser Permanente Northern California (KPNC) Member Health Survey (MHS) is used to describe sociodemographic and health-related characteristics of the adult membership of this large, integrated health care delivery system to monitor trends over time, identify health disparities, and conduct research. OBJECTIVE: To provide an overview of the KPNC MHS and share findings that illustrate how survey statistics and data have been and can be used for research and programmatic purposes. METHODS: The MHS is a large-scale, institutional review board-approved survey of English-speaking KPNC adult members. The confidential survey has been conducted by mail triennially starting in 1993 with independent age-sex and geographically stratified random samples, with an option for online completion starting in 2005. The full survey sample and survey data are linkable at the individual level to Health Plan and geocoded data. Respondents are assigned weighting factors for their survey year and additional weighting factors for analysis of pooled survey data. RESULTS: Statistics from the 1999, 2002, 2005, 2008, and 2011 surveys show trends in sociodemographic and health-related characteristics and access to the Internet and e-mail for the adult membership aged 25 to 79 years and for 6 age-sex subgroups. Pooled data from the 2008 and 2011 surveys show many significant differences in these characteristics across the 5 largest race/ethnic groups in KPNC (non-Hispanic whites, blacks, Latinos, Filipinos, and Chinese). CONCLUSION: The KPNC MHS has yielded unique insights and provides an opportunity for researchers and public health organizations outside of KPNC to leverage our survey-generated statistics and collaborate on epidemiologic and health services research studies. PMID- 27548808 TI - Large-Scale Spinning of Silver Nanofibers as Flexible and Reliable Conductors. AB - Conducting metal nanowires can be assembled into thin films for flexible electronics and optoelectronics applications including transparent electrodes, nanocircuits, and electronic skin, however, the junction resistances and low aspect ratios still limit its performance. Herein we report high-quality silver nanofibers (AgNFs) synthesized by a gas-assistant solution spinning method. Compared with traditional Ag nanowires that usually have lengths below 100 MUm, AgNFs are infinitely long and can be easily assembled into large-scale 2D and 3D flexible conductors with fused junctions between nanofibers. The AgNF networks showed high transparency, low sheet resistance (e. g, 6 Omega sq(-1) at ~97% transparency), and high flexibility as transparent electrodes, whereas the 3D AgNF sponge could be used as a deformable and robust 3D conductor. PMID- 27548807 TI - Shrinkage-mediated imaging of entire organs and organisms using uDISCO. AB - Recent tissue-clearing approaches have become important alternatives to standard histology approaches. However, light scattering in thick tissues and the size restrictions on samples that can be imaged with standard light-sheet microscopy pose limitations for analyzing large samples such as an entire rodent body. We developed 'ultimate DISCO' (uDISCO) clearing to overcome these limitations in volumetric imaging. uDISCO preserves fluorescent proteins over months and renders intact organs and rodent bodies transparent while reducing their size up to 65%. We used uDISCO to image neuronal connections and vasculature from head to toe over 7 cm and to perform unbiased screening of transplanted stem cells within the entire body of adult mice. uDISCO is compatible with diverse labeling methods and archival human tissue, and it can readily be used in various biomedical applications to study organization of large organ systems throughout entire organisms. PMID- 27548810 TI - Omitted Financial Disclosure and Typos. PMID- 27548809 TI - A Small-Molecule Inhibitor of Lin28. AB - New discoveries in RNA biology underscore a need for chemical tools to clarify their roles in pathophysiological mechanisms. In certain cancers, synthesis of the let-7 microRNA tumor suppressor is blocked by an RNA binding protein (RBP) Lin28, which docks onto a conserved sequence in let-7 precursor RNA molecules and prevents their maturation. Thus, the Lin28/let-7 interaction might be an attractive drug target, if not for the well-known difficulty in targeting RNA protein interactions with drugs. Here, we describe a protein/RNA FRET assay using a GFP-Lin28 donor and a black-hole quencher (BHQ)-labeled let-7 acceptor, a fluorescent protein/quencher combination which is rarely used in screening despite favorable spectral properties. We tested 16 000 molecules and identified N-methyl-N-[3-(3-methyl[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl]acetamide, which blocked the Lin28/let-7 interaction, rescued let-7 processing and function in Lin28-expressing cancer cells, induced differentiation of mouse embryonic stem cells, and reduced tumor-sphere formation by 22Rv1 and Huh7 cells. A biotinylated derivative captured Lin28 from cell lysates consistent with an on-target mechanism in cells, though the compound also showed some activity against bromodomains in selectivity assays. The Lin28/let-7 axis is presently of high interest not only for its role as a bistable switch in stem-cell biology but also because of its prominent roles in numerous diseases. We anticipate that much can be learned from the use of this first reported small molecule antagonist of Lin28, including the potential of the Lin28/let-7 interaction as a new drug target for selected cancers. Furthermore, this approach to assay development may be used to identify antagonists of other RBP/RNA interactions suspected to be operative in pathophysiological mechanisms. PMID- 27548811 TI - Sulfone-Rhodamines: A New Class of Near-Infrared Fluorescent Dyes for Bioimaging. AB - Given the wavelength dependence of tissue transparency and the requirement for sufficiently low background autofluorescence, the development of fluorescent dyes with excitation and emission maxima beyond 700 nm is highly desired, but it is a challenging task. Herein, a new class of fluorescent dyes, named sulfone rhodamines (SO2Rs), was developed on the basis of the one-atom replacement of the rhodamine 10-position O atom by a sulfone group. Such a modification makes their absorption and emission maxima surprisingly reach up to 700-710 and 728-752 nm, respectively, much longer than their O-, C-, and Si-rhodamine analogs, due to the unusual d*-pi* conjugation. Among these dyes, SO2R4 and SO2R5, bearing disubstituted meso-phenyl groups, show the greatest potentials for bioimaging applications in view of their wide pH range of application, high photostability, and big extinction coefficients and fluorescence quantum yields. They could quickly penetrate cells to give stable NIR fluorescence, even after continuous irradiation by a semiconductor laser, making them suitable candidates for time lapse and long-term bioimaging applications. Moreover, they could specifically localize in lysosomes independent of alkylmorpholine targeted group, thus avoiding the problematic alkalization effect suffered by most LysoTrackers. Further imaging assays of frozen slices of rat kidney reveal that their tissue imaging depth is suprior to the widely used NIR labeling agent Cy5.5. PMID- 27548812 TI - IDH1/2 Mutants Inhibit TET-Promoted Oxidation of RNA 5mC to 5hmC. AB - TETs (TET1/2/3) play critical roles in multi cellular processes through DNA demethylation driven by oxidation of DNA 5mdC to 5hmdC. Interestingly, recent studies indicated that TETs also oxidate RNA 5mC to 5hmC. However, little is known about the distribution of RNA 5hmC and the regulatory mechanism of RNA 5hmC in human. Here, we show that 5hmC is enriched in mRNA, and IDH1/2 mutants inhibit TET-promoted oxidation of RNA 5mC to 5hmC. Since IDH1/2 mutations have been described to block the DNA oxidative activity of TETs, we hypothesized that IDH1/2 mutations might also inhibit the RNA oxidative activity of TETs. To evaluate the role of IDH1/2 mutations in RNA 5hmC, TETs with/without IDH1/2 mutants were overexpressed in human HEK293 cells. Resultant DNA and RNA were digested and analyzed by triple-quadrupole LC mass spectrometer. DNA 5hmdC and RNA 5hmC modifications were quantified with external calibration curves of appropriate standards. It was found that compared with total RNA (5hmC/C: less than 2 X 10-7), mRNA showed much higher 5hmC level (5hmC/C: ~7 X 10-6). Further study indicated that IDH1/2 mutants showed significant ability to inhibit TET promoted RNA5hmC. Consistent with this result, overexpression of IDH1/2 mutants also inhibited TET catalytic domain-promoted oxidation of RNA. In this study, we show not only the enrichment of 5hmC in mRNA, but also a regulatory mechanism of RNA 5hmC-IDH1/2 mutations inhibit TET-promoted RNA 5hmC, which suggests an involvement of IDH1/2 mutations in tumorigenesis through the deregulation of RNA biology. PMID- 27548814 TI - Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype. AB - Neuroendocrine tumors (NETs), which can have survival rates as low as 4%, currently have limited therapeutic interventions available highlighting the dire need for the identification of novel biological targets for use as new potential drug targets. One such potential target is retinoblastoma-binding protein 2 (RBP2), an H3K4 demethylase whose overexpression has been linked to cancer formation and metastasis in non-endocrine tumor types. We measured RBP2 mRNA and protein levels in enteropancreatic NETs by measuring RBP2 in matched human normal and NET tissue samples. Further, proliferation, migration, invasion and colony formation assays were performed in the physiologically relevant NET cell lines betalox5, H727 and QGP-1 to understand the role of RBP2 and its demethylase activity on end points of tumorigenesis. Our data indicate a strong correlation between RBP2 mRNA and protein expression in NET specimens. RBP2 was overexpressed relative to tissue-matched normal controls in 80% of the human tumors measured. In vitro studies showed RBP2 overexpression significantly increased proliferation, migration, invasion and colony formation, whereas knockdown significantly decreases the same parameters in a demethylase-independent manner. The cell cycle inhibitors p21 and p57 decreased with RBP2 overexpression and increased upon its depletion, suggesting a regulatory role for RBP2 in cellular proliferation. Taken together, our results support the hypothesis that the aberrant overexpression of RBP2 is a frequent contributing factor to tumor formation and metastasis in enteropancreatic NETs. PMID- 27548813 TI - Molecular, Structural and Immunological Characterization of Der p 18, a Chitinase Like House Dust Mite Allergen. AB - BACKGROUND: The house dust mite (HDM) allergen Der p 18 belongs to the glycoside hydrolase family 18 chitinases. The relevance of Der p 18 for house dust mite allergic patients has only been partly investigated. OBJECTIVE: To perform a detailed characterization of Der p 18 on a molecular, structural and immunological level. METHODS: Der p 18 was expressed in E. coli, purified to homogeneity, tested for chitin-binding activity and its secondary structure was analyzed by circular dichroism. Der p 18-specific IgG antibodies were produced in rabbits to localize the allergen in mites using immunogold electron microscopy and to search for cross-reactive allergens in other allergen sources (i.e. mites, crustacea, mollusca and insects). IgE reactivity of rDer p 18 was tested with sera from clinically well characterized HDM-allergic patients (n = 98) and its allergenic activity was analyzed in basophil activation experiments. RESULTS: Recombinant Der p 18 was expressed and purified as a folded, biologically active protein. It shows weak chitin-binding activity and partial cross-reactivity with Der f 18 from D. farinae but not with proteins from the other tested allergen sources. The allergen was mainly localized in the peritrophic matrix of the HDM gut and to a lower extent in fecal pellets. Der p 18 reacted with IgE from 10% of mite allergic patients from Austria and showed allergenic activity when tested for basophil activation in Der p 18-sensitized patients. CONCLUSION: Der p 18 is a rather genus-specific minor allergen with weak chitin-binding activity but exhibits allergenic activity and therefore should be included in diagnostic test panels for HDM allergy. PMID- 27548815 TI - Minimum information required for a DMET experiment reporting. AB - AIM: To provide pharmacogenomics reporting guidelines, the information and tools required for reporting to public omic databases. MATERIAL & METHODS: For effective DMET data interpretation, sharing, interoperability, reproducibility and reporting, we propose the Minimum Information required for a DMET Experiment (MIDE) reporting. RESULTS: MIDE provides reporting guidelines and describes the information required for reporting, data storage and data sharing in the form of XML. CONCLUSION: The MIDE guidelines will benefit the scientific community with pharmacogenomics experiments, including reporting pharmacogenomics data from other technology platforms, with the tools that will ease and automate the generation of such reports using the standardized MIDE XML schema, facilitating the sharing, dissemination, reanalysis of datasets through accessible and transparent pharmacogenomics data reporting. PMID- 27548816 TI - Critical reflections on the currently leading definition of sustainable employability. AB - Sustainable employability (SE) is an important topic as it deals with employees' abilities to function adequately at work and in the labor market throughout their working lives. However, until now there has been only one attempt to define SE in the international literature (1). This first definition is a valuable contribution to the field as it rightfully describes SE as a multidimensional concept, recognizes the importance of both employee and work characteristics, and acknowledges the inherently longitudinal nature of SE. Despite these merits, we argue that this definition of SE has some serious omissions that are important in capturing SE comprehensively. Specifically, we argue that the definition could be improved in various ways, namely, it should: (i) clarify which aspects of employment constitute someone's SE; (ii) not counterintuitively treat SE as a characteristic of both the job and the employee simultaneously; (iii) not be based on the insufficiently tested assumption that achieving value in work inherently leads to SE; (iv) be formulated in a way that SE can also apply to unemployed individuals; and (v) adequately specify how the inherently longitudinal dimension of SE should be addressed. We would like to contribute to the discussion by providing guidelines for a new adjusted definition of SE that could facilitate further research on this important concept and its determinants. Introduction SE is a topic of vital importance to individual employees, organizations and society alike. It generally refers to employees' capacities to function in work throughout their working life. As participation in work is important for individuals, organizations, and society as a whole, individuals' ability to function in work is essential. For individuals, work provides meaning, financial security as well as social contacts. Organizations need productive employees to survive. Also from a societal perspective, it is important that as many people as possible participate in the labor market to maintain economic welfare (1). Moreover, as a consequence of population aging (2-6), longevity, rapid changes in technology (7, 8) and changes in the nature of work (1), both the need to promote sustainable employability of individuals in society and the complexity to succeed in doing so increase even further. Only recently, van der Klink et al provided the first definition of the concept in the international scientific literature (1, p74): "Sustainable employability means that throughout their working lives, workers can achieve tangible opportunities in the form of a set of capabilities. They also enjoy the necessary conditions that allow them to make a valuable contribution through their work, now and in the future, while safeguarding their health and welfare. This requires, on the one hand, a work context that facilitates this for them and, on the other, the attitude and motivation to exploit these opportunities." This definition is accompanied by an equally recent operationalization of SE as a set of capabilities (9). Moreover, the definition itself also appeared in an earlier Dutch publication (10), which other international publications about SE most commonly refer to [ie, in comparison with other definitions in the non-international (eg, Dutch) literature] (11-13). As mentioned, the present paper provides a critical reflection on van der Klink et al's aforementioned definition of SE (1). Merits Van der Klink et al's definition of SE (1) has three important merits. First, SE is seen as a multidimensional construct. It is presented as consisting of a broad set of opportunities for employees to create value for themselves and for their employer that cover various aspects of working. Moreover, the individual's health and well-being as well as attitudinal and motivational aspects are included in the definition as well. This acknowledgement of the multidimensionality of SE is favorable, as it illustrates the complexity of the construct and of what constitutes functioning in work. This is in accordance with the International Classification of Functioning, Disability and Health (ICF) (14), in which functioning is seen from three different perspectives (body, activities, and participation). The ICF underlines the multifaceted and complex nature of functioning in which disease, environmental factors, and personal factors play a role. Similarly, the multifaceted nature of functioning is also illustrated by the fact that different disciplines focus on different aspects to understand functioning at work (15, 16). Second, SE is (partially) defined as the degree to which (i) employees are able to work throughout their entire working lives, and (ii) their work context enables them to do so. This suggests that SE is a set of interacting characteristics of the employee and the work context that codetermine the opportunities and conditions affecting employees' capacity to participate in the labor market throughout their working lives. As such, the definition describes an equal responsibility for employee and employer to maintain the employee's ability to work. This could be considered as a great merit, as research shows how strongly an employee's ability to function is influenced by both the individual, work and work-contextual factors (17). Third, van der Klink et al's definition recognizes that SE is an inherently longitudinal construct as clearly embedded in the words "throughout their working lives". This is essential as "sustainable" necessarily implies a time dimension. Need for further development Despite the aforementioned merits, there are important needs for improvement of van der Klink et al's definition of SE. First, it is not immediately clear from the definition what particular element(s) of the work situation constitute(s) SE. The paper provides some clarity by equating SE with the capability set it propagates, as evidenced by these statements: "... in an accompanying paper also published in this issue, we report on the development and validation of a questionnaire that allows for the assessment of sustainable employability based on the concept of capability" (1, p72) and "This [capability] set, in our view, represents the best possible operationalization of sustainable employability" (1, p74). However, in the paper, SE is also referred to as being determined by a worker's capability: "this model holds that an individual's sustainable employability is determined by how he or she succeeds in converting resources into capabilities, and subsequently into work functioning, in such a way that values such as security, recognition and meaning are met"(1, p72). As it is not feasible that SE is predicted by itself in the form of a capability set, perhaps the capability set does not actually refer to SE itself but rather to a favorable employment situation that may cause SE. More clarity on this issue is needed. Second, the definition seems to treat SE as a characteristic of both the job and the individual at the same time. This is counterintuitive and problematic as the job and work context may predict an individual's ability to be sustainably employed, but they can never be aspects that are part of SE. Instead, employability is a characteristic of the individual alone. Of course the individual's ability to be employed does depend on work and work-contextual factors, but these should be predictors and not be embedded in the construct itself. For an adequate definition of SE, it is essential to disentangle these relationships between causes (employment) and effects (employability). Moreover, future approaches should treat SE as an individual characteristic that is an outcome of the complex interaction between other individual, work, and work contextual characteristics. Third, the definition and operationalization of SE assume that achieving value in work inherently predicts SE and that, therefore, SE can be conceptualized as achieving value in work. This is problematic, as before such claims can be made, such relationships need to be tested with SE as criterion. This is, however, impossible within the approach van der Klink et al provides. (1), as SE is equated with its predictor(s). Therefore, similar to the first conceptual issue, it seems unlikely that the capability set adequately reflects SE. Fourth, the definition by van der Klink et al (1) suggests that SE only applies to individuals who are employed. In the Abma et al publication (9), which accompanies van der Klink's definition paper as a validation paper, this is shown by the way in which capabilities are measured. Moreover, the definition also suggests this because individuals can only be considered to be sustainably employable if their work context enables them to achieve tangible opportunities. However, individuals who are not currently working can still be highly employable and even sustainably so, but just be between jobs. It is therefore not required for individuals to be enabled by their employer to be sustainably employable. Consequently, in line with our aforementioned points on improving the definition, being enabled by an employer to achieve value may be an important predictor of SE, but it is not necessarily part of SE itself. Moreover, future approaches to SE should define the concept in such a way that it is applicable to every individual regardless of employment status. Finally, the definition and operationalization of SE in the form of a capability set do not include any specification on how the longitudinal aspect of SE should be captured. The definition rightfully acknowledges the longitudinal dimension of SE, but its operationalization focuses solely on achieving value. Although achieving value at work may be an important predictor of SE, a complete operationalization and definition should include its longitudinal nature as well. Outlook In conclusion, while van der Klink et al's definition of SE (1) does have strong merits, it requires further improvement. The approach's main drawback is that capabilities seem more apt at describing a potentially important set of predictor(s) of SE than at capturing the construct itself. Either way, future developments in conceptualizing SE should build on the aforementioned merits, but also define SE in a way that (i) clearly labels which aspects of the employment situation constitute SE; (ii) explicitly separates causes and effects; (iii) treats SE as an individual characteristic that may be affected by other employment characteristics at the individual, work, and work-contextual levels; (iv) makes the concept applicable to any individual regardless of their employment status; and (v) clearly addresses the longitudinal nature of SE as embedded in the word "sustainable". These guidelines should not only enable the development of an appropriate definition of SE but also a conceptually sound way of measuring the construct. PMID- 27548817 TI - Fluorination methods for drug discovery and development. AB - INTRODUCTION: The pivotal role that the element fluorine plays in modulating the properties of bioactive molecules is reflected by the growth of its presence in approved drugs. In 1970, approximately 2% of drugs contained fluorine with this number rising to 25% by 2011. The synthetic chemistry regarding incorporation of fluorine into organic molecules has also evolved over this time with a paradigm shift from harsh, toxic, hazardous reagents utilized primarily by specialist vendors to new deoxyfluorination reagents and metal-mediated techniques capable of the precise introduction of fluorine into complex organic substrates under relatively mild conditions. AREAS COVERED: This review highlights the importance of fluorinated compounds in drug discovery, and provides an overview on the synthetic strategies and methodologies developed to access them both in discovery and development. EXPERT OPINION: The development of new reagents for the safe and precise regioselective fluorination of biologically relevant compounds particularly in drug discovery remains a contemporary challenge in organic chemistry. However, significant strides have been made with the development of new deoxyfluorination reagents and the emergence of practical metal-mediated fluorination techniques have enabled the goal of efficient late-stage fluorination of drug-like compounds to be realized, and the extension of these methods for PET-labelling is being investigated. PMID- 27548818 TI - Development and Validation of a Score to Predict Mortality in Children Undergoing Extracorporeal Membrane Oxygenation for Respiratory Failure: Pediatric Pulmonary Rescue With Extracorporeal Membrane Oxygenation Prediction Score. AB - OBJECTIVE: Our objective was to develop and validate a prognostic score for predicting mortality at the time of extracorporeal membrane oxygenation initiation for children with respiratory failure. Preextracorporeal membrane oxygenation mortality prediction is important for determining center-specific risk-adjusted outcomes and counseling families. DESIGN: Multivariable logistic regression of a large international cohort of pediatric extracorporeal membrane oxygenation patients. SETTING: Multi-institutional data. PATIENTS: Prognostic score development: A total of 4,352 children more than 7 days to less than 18 years old, with an initial extracorporeal membrane oxygenation run for respiratory failure reported to the Extracorporeal Life Support Organization's data registry during 2001-2013 were used for derivation (70%) and validation (30%). Bidirectional stepwise logistic regression was used to identify factors associated with mortality. Retained variables were assigned a score based on the odds of mortality with higher scores indicating greater mortality. External validation was accomplished using 2,007 patients from the Pediatric Health Information System dataset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction score included mode of extracorporeal membrane oxygenation; preextracorporeal membrane oxygenation mechanical ventilation more than 14 days; preextracorporeal membrane oxygenation severity of hypoxia; primary pulmonary diagnostic categories including, asthma, aspiration, respiratory syncytial virus, sepsis-induced respiratory failure, pertussis, and "other"; and preextracorporeal membrane oxygenation comorbid conditions of cardiac arrest, cancer, renal and liver dysfunction. The area under the receiver operating characteristic curve for internal and external validation datasets were 0.69 (95% CI, 0.67-0.71) and 0.66 (95% CI, 0.63-0.69). CONCLUSIONS: Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction is a validated tool for predicting in-hospital mortality among children with respiratory failure receiving extracorporeal membrane oxygenation support. PMID- 27548819 TI - Systemic Adenosine Triphosphate Impairs Neutrophil Chemotaxis and Host Defense in Sepsis. AB - OBJECTIVE: Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding of the underlying pathophysiology of sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels that fuel autocrine feedback via purinergic receptors. In the current study, we examined the roles of endogenous and systemic adenosine triphosphate on polymorphonuclear neutrophil activation and host defense in sepsis. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Preclinical academic research laboratory. SUBJECTS: Wild-type C57BL/6 mice, pannexin-1 knockout mice, and healthy human subjects used to obtain polymorphonuclear neutrophils for in vitro studies. INTERVENTIONS: Wild-type and pannexin-1 knockout mice were treated with suramin or apyrase to block the endogenous or systemic effects of adenosine triphosphate. Mice were subjected to cecal ligation and puncture and polymorphonuclear neutrophil activation (CD11b integrin expression), organ (liver) injury (plasma aspartate aminotransferase), bacterial spread, and survival were monitored. Human polymorphonuclear neutrophils were used to study the effect of systemic adenosine triphosphate and apyrase on chemotaxis. MEASUREMENTS AND MAIN RESULTS: Inhibiting endogenous adenosine triphosphate reduced polymorphonuclear neutrophil activation and organ injury, but increased the spread of bacteria and mortality in sepsis. By contrast, removal of systemic adenosine triphosphate improved bacterial clearance and survival in sepsis by improving polymorphonuclear neutrophil chemotaxis. CONCLUSIONS: Systemic adenosine triphosphate impairs polymorphonuclear neutrophil functions by disrupting the endogenous purinergic signaling mechanisms that regulate cell activation and chemotaxis. Removal of systemic adenosine triphosphate improves polymorphonuclear neutrophil function and host defenses, making this a promising new treatment strategy for sepsis. PMID- 27548820 TI - Vascular Endothelial Growth Factor Up-regulation in Human Amniotic Fluid Stem Cell Enhances Nephroprotection After Ischemia-Reperfusion Injury in the Rat. AB - OBJECTIVE: To evaluate if the up-regulation of vascular endothelial growth factor strengthens the protective effect of amniotic fluid stem cells in a renal ischemia-reperfusion injury model. DESIGN: Randomized animal study. SETTINGS: University research laboratory. SUBJECTS: A total of 40 males 12-week-old Wistar rats were subjected to ischemia-reperfusion and assigned to four groups: amniotic fluid stem cells, vascular endothelial growth factor-amniotic fluid stem cells in two different doses, and vehicle. Ten animals were used as sham-controls. INTERVENTION: Six hours after induction of renal ischemia-reperfusion injury, amniotic fluid stem cells, vascular endothelial growth factor-amniotic fluid stem cells in two different doses, or vehicle were injected intraarterially. MEASUREMENTS AND MAIN RESULTS: Analyses were performed at 24 hours, 48 hours, and 2 months after treatment. Outcome measures included serum creatinine, urine microprotenuira, and immunohistomorphometric analyses. Vascular endothelial growth factor-amniotic fluid stem cells induced a significantly higher nephroprotection than amniotic fluid stem cells. This effect was mediated mainly by immunomodulation, which led to lower macrophage infiltration and higher presence of regulatory T cell after ischemia-reperfusion injury. At medium term, it inhibited the progression toward chronic kidney disease. Vascular endothelial growth factor-amniotic fluid stem cells can worsen the ischemia-reperfusion injury when delivered in a high dose. CONCLUSIONS: Up-regulation of vascular endothelial growth factor enhances the therapeutic effect of human amniotic fluid stem cells in rats with renal ischemia-reperfusion injury, mainly by mitogenic, angiogenic, and anti-inflammatory mechanisms. PMID- 27548821 TI - Serum Uric Acid Exhibits Inverse Relationship with Estimated Glomerular Filtration Rate. AB - BACKGROUND: In this study, we investigated the relationship between serum uric acid (SUA) and renal function in a unique patient cohort wherein SUA levels fluctuate during the course of standard care. METHODS: Correlation coefficients between SUA and serum creatinine (SCr) and kinetic estimated GFR (KeGFR) were retrospectively investigated in acute myeloid leukemia (AML) patients, and statistically significant and clinically relevant determinants were studied in multiple regression models. RESULTS: One hundred and twenty-six patients were included in the analysis. Baseline SUA was associated with an increased risk for acute kidney injury (AKI; OR 1.27, 95% CI 1.1-1.5, p = 0.003) and laboratory tumor lysis syndrome (OR 1.26, 95% CI 1.1-1.5, p = 0.005). Prophylactic uric acid lowering therapy and hydration resulted in lower SUA values from baseline in 88.1% of the patients, the lowest values were observed on post-induction day 1 (20.4% reduction). Significant linear correlations were observed between SUA and SCr (r = 0.35, p < 0.001) values with a significant inverse correlation between SUA and KeGFR on day 1 (r = -0.33, p < 0.001) that persisted through day 4. By subgroup analysis, patients with primary AML (r = -0.49, p < 0.001), baseline SUA >5.5 mg/dl (r = -0.41, p = 0.002) and baseline eGFR >60 ml/min/1.73 m2 (r = 0.51, p < 0.001) demonstrated robust relationships between SUA and KeGFR. The relationship was more robust when the groups were combined (primary AML plus baseline SUA >5.5 mg/dl plus baseline eGFR >60 ml/min/1.73 m2, r = -0.52, p < 0.001). CONCLUSION: The demonstration of linear relationship between SUA and SCr and inverse relationship between SUA and KeGFR reinforces the emerging translational physiological evidence regarding the role of uric acid in AKI. PMID- 27548822 TI - Extrahepatic Diseases and NAFLD: The Triangular Relationship between NAFLD, Type 2-Diabetes and Dysbiosis. AB - Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases from simple steatosis with hepatic lipid accumulation to end-stage liver disease with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Recent data from the USA showed that in 2013, NAFLD was the second most frequent indication for liver transplantation behind hepatitis C. Since there are now effective treatments for hepatitis C and there is currently no licensed treatment for NAFLD, it has been predicted that over the next 10-15 years, NAFLD will replace hepatitis C as the most frequent indication for liver transplantation. Besides, increasing the risk of hepatocellular carcinoma and end-stage liver disease, it has recently become clear that NAFLD also increases risk of extrahepatic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, cardiac diseases and chronic kidney disease, to name but a few. Of each of these extrahepatic diseases, the evidence to date suggests that NAFLD is a strong risk factor for T2DM. When NAFLD occurs in combination with obesity and insulin resistance (as it frequently does), there is a marked increase in risk of incident T2DM with possible synergism occurring between liver fat accumulation, insulin resistance and obesity to further increase risk of development of T2DM. Thus, there is a reciprocal relationship between NAFLD as a risk factor for T2DM, and T2DM as a risk factor for liver disease progression in NAFLD. Moreover, recent evidence now points to the importance of perturbation of the intestinal microbiota (dysbiosis) in both T2DM and NAFLD. Consequently, there is a triangular relationship between dysbiosis and T2DM and NAFLD. This review will focus on T2DM as a key extrahepatic complication of NAFLD and will describe and discuss the triangular relationship between dysbiosis and T2DM and NAFLD and the factors and potential mechanisms underpinning this relationship. PMID- 27548823 TI - The biology of environmental stress: molecular biomarkers in Sydney rock oysters (Saccostrea glomerata). AB - This review describes our recent work on environmental stress in Sydney rock oysters, focusing on the identification of molecular biomarkers for ecotoxicological analysis. We begin by describing the environmental pressures facing coastal estuaries in Australia, with particular reference to Sydney Harbour. After providing that context, we summarise our transcriptional and proteomic analyses of Sydney rock oysters responding to chemical contamination and other forms of environmental stress. This work has shown that the intracellular processes of oysters are highly responsive to environmental threats. Our data agree with the broader literature, which suggests that there is a highly conserved intracellular stress response in oysters involving a limited number of biological processes. We conclude that many effective molecular markers for environmental biomonitoring are likely to lie within these biological pathways. PMID- 27548824 TI - Refolding of Aggregation-Prone ScFv Antibody Fragments Assisted by Hydrophobically Modified Poly(sodium acrylate) Derivatives. AB - ScFv antibody fragments are a promising alternative to full-length antibodies for both therapeutic and diagnosis applications. They can be overexpressed in bacteria, which enables easy large scale production. Since scFv are artificial constructs, they are poorly soluble and prone to aggregation, which makes them difficult to manipulate and to refold. Here, stabilization and refolding of scFv fragments from urea-unfolded solutions are reported based on the use of micromolar amounts of polymers playing the role of artificial chaperons. Using fluorescence correlation spectroscopy, the size and aggregation number of complexes of scFv with unmodified or hydrophobically modified poly(sodium acrylate) are determined. The evolution of the secondary structure along the refolding procedure, in the presence or absence of 0.4 m l-arginine at scFv:polymer < 1:5 (w/w), is determined by high-sensitivity synchrotron-radiation circular dichroism. Measurements reveal that refolding in the presence of polymers yields native-like secondary structure, though a different folding pathway can be followed compared to refolding in the absence of polymer. This is the first report on the use of macromolecular additives to assist refolding of a multidomain protein of therapeutic interest. PMID- 27548825 TI - Utilizing selection biomarkers in clinical trials: is this the future of drug development? PMID- 27548826 TI - A Systematic Review of the Effectiveness of Tongue Lip Adhesion in Improving Airway Obstruction in Children With Pierre Robin Sequence. AB - BACKGROUND: Tongue-lip adhesion (TLA) involves surgically tethering the tongue forward to the lower lip and is a technique to relieve airway obstruction caused by glossoptosis and retrognathia. The purpose of the present study was to evaluate the effectiveness of TLA for the treatment of airway compromise in patients with Pierre Robin sequence (PRS). METHODS: A comprehensive literature review was performed. Inclusion criteria consisted of patients having undergone isolated tongue lip adhesion and results that included airway outcome. Selected manuscripts were analyzed with regards to patient demographics, principle diagnosis, pre and postintervention airway status, and complications. RESULTS: Thirteen manuscripts met inclusion criteria, yielding 268 patients with PRS who underwent TLA. The mean age at the time of procedure was 30.5 days. Tongue lip adhesion proved to be successful in relieving airway obstruction caused by PRS in 81.3% (n = 218) of patients. Nonsyndromic patients benefited from a higher success rate as compared with the syndromic cohort (91.5% and 79.8% respectively, P = 0.0361). Eight patients who were initially successfully managed with TLA required a repeat procedure due to dehiscence. CONCLUSIONS: Tongue-lip adhesion is a safe and effective technique and is associated with lower morbidity and mortality as compared with mandibular distraction osteogenesis and tracheostomy and should be considered in patients with PRS who fail conservative management. The greater success and lower complication rates in nonsyndromic patients reinforce the importance of proper patient selection and consideration of other techniques such as mandibular distraction osteogenesis should be given in patients with associated syndromic diagnoses. PMID- 27548827 TI - Commentary on: Utility of Prophylactic Antibiotics in Nonoperative Facial Fractures. PMID- 27548828 TI - Resorbable Mesh as a Containment System in Mandibular Reconstruction. AB - The recent advances seen in computer technologies and biomaterials have changed the approach to craniomaxillofacial surgery. In this report, the authors describe the technique of using a resorbable containment system for bone graft in a large mandibular reconstruction patient. The authors provide a patient report with a 1 year follow-up. PMID- 27548831 TI - Simultaneous Computer-Aided Design/Computer-Aided Manufacture Bimaxillary Orthognathic Surgery and Mandibular Reconstruction Using Selective-Laser Sintered Titanium Implant. AB - This patient report describes simultaneous bimaxillary orthognathic surgery and mandibular reconstruction by means of three-dimensional (3D) planning, 3D printed biocompatible surgical wafers, and 3D selective-laser sintered titanium implant. A 26-year-old male patient presented with a left mandibular defect secondary to trauma. The whole body of the mandible on the left hand side was deficient with a narrow connection with the remaining left condyle. He had undergone orthodontic treatment for 18 months and was ready to undergo bimaxillary orthognathic surgery. Advanced cranio-maxillofacial software was used in processing his cone beam computer tomography scan data, and e-casts of his upper and lower dental arches. Bimaxillary surgery was planned with Le Fort 1 maxillary impaction and mandibular advancement to achieve a class 1 incisor relationship. Intermediate and final surgical wafers were designed following the planned movements and printed using biocompatible resin. The deficient left side of the mandible was reconstructed by means of mirror imaging the contra-lateral right side into the deficient left side with the aim of restoring normal facial symmetry. Biomedical software was then used in designing a reconstruction plate that connected the condylar head and the mandible following the planned bimaxillary surgery and mandibular continuity symmetry reconstruction. The plate was printed in titanium following state-of the-art selective laser sintering technology. The bimaxillary surgery and mandibular reconstruction were done simultaneously as planned along with an iliac-crest bone graft. This patient confirms the advantages of 3D computer-aided design/computer-aided manufacture technologies in optimizing clinical outcomes for cranio-maxillofacial reconstruction, especially when conducting two simultaneous clinical procedures. PMID- 27548832 TI - Micromarsupialization: A Minimally Invasive Alternative for Treatment of a Large Oral Ranula. PMID- 27548833 TI - Effect of Osteoporosis on Bone Density of Orthognathic Osteotomy Sites in Maxillofacial Region. AB - OBJECTIVES: The aims of this study were to investigate the availability of Hounsfield unit (HU) measurement of computed tomography (CT) in evaluating the bone density of certain sites by comparing bone density between CT and dual energy x-ray absorptiometry (DEXA), and to evaluate the effects of osteoporosis on osteotomy sites in orthognathic surgery. METHODS: This retrospective study included 80 patients who had undergone both facial CT and DEXA at our hospital. We selected 7 regions of interest from among the osteotomy sites in bimaxillary orthognathic surgery. The patients were assigned to either the normal (control) group (n = 40) or the abnormal group (n = 40), and HU values were measured in each region of interest. RESULTS: There were statistically significant differences in the mean HU values between 2 groups at all the osteotomy sites in the maxilla and mandible, with the normal group showing higher values than the abnormal group (P < 0.05). In addition, there was a significant positive correlation between T-scores obtained with DEXA and the HU values on CT at the osteotomy sites (P < 0.01). Multiple regression analysis indicated that the abnormal group was more negatively associated with 6 osteotomy sites except for 1 maxillary area, as compared with the normal group. CONCLUSIONS: Measurement of HU values on CT can be valuable in assessing bone density of the maxilla and mandible. It is suggested that osteoporosis may affect bone density at the osteotomy sites in orthognathic surgery, and the preoperative measurement of HU values might be useful in predicting unfavorable fracture or the risks involved in such surgery. PMID- 27548834 TI - Investigational and experimental drugs for intraocular pressure reduction in ocular hypertension and glaucoma. AB - INTRODUCTION: Intraocular pressure (IOP) is the most significant modifiable risk factor to prevent onset or progression of glaucoma. Glaucoma prevalence continues to increase, emphasizing the need for improved ocular hypotensive treatment options. To try to improve on both tolerance and IOP control of currently available therapies, different receptors or mechanisms are being explored to reduce IOP more effectively and to improve tolerance. AREAS COVERED: We review synthetic topical and oral drugs in early development for the management of ocular hypertension and glaucoma. EXPERT OPINION: New therapeutic agents for IOP control have been discovered; some appear to be reasonably tolerated. IOP reduction may be limited with some agents, but other benefits although unproven may compensate for this, such as less ocular surface disease, enhanced neuro protection or increased ocular blood flow. Further product development promises improved treatment options for ocular hypertensives and glaucoma sufferers. PMID- 27548835 TI - Dopamine dysfunction in 22q11 deletion syndrome: possible cause of motor symptoms. AB - 22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS. PMID- 27548837 TI - Extension of influenza immunization program to children in England - Future plans. PMID- 27548836 TI - (2 + 1)D-CAIPIRINHA accelerated MR spectroscopic imaging of the brain at 7T. AB - PURPOSE: To compare a new parallel imaging (PI) method for multislice proton magnetic resonance spectroscopic imaging (1 H-MRSI), termed (2 + 1)D-CAIPIRINHA, with two standard PI methods: 2D-GRAPPA and 2D-CAIPIRINHA at 7 Tesla (T). METHODS: (2 + 1)D-CAIPIRINHA is a combination of 2D-CAIPIRINHA and slice CAIPIRINHA. Eight healthy volunteers were measured on a 7T MR scanner using a 32 channel head coil. The best undersampling patterns were estimated for all three PI methods. The artifact powers, g-factors, Cramer-Rao lower bounds (CRLB), and root mean square errors (RMSE) were compared quantitatively among the three PI methods. Metabolic maps and spectra were compared qualitatively. RESULTS: (2 + 1)D-CAIPIRINHA allows acceleration in three spatial dimensions in contrast to 2D GRAPPA and 2D-CAIPIRINHA. Thus, this sequence significantly decreased the RMSE of the metabolic maps by 12.1 and 6.9%, on average, for 4 < R < 11, compared with 2D GRAPPA and 2D-CAIPIRINHA, respectively. The artifact power was 22.6 and 8.4% lower, and the CRLB were 3.4 and 0.6% lower, respectively. CONCLUSION: (2 + 1) CAIPIRINHA can be implemented for multislice MRSI in the brain, enabling higher accelerations than possible with two-dimensional (2D) parallel imaging methods. An eight-fold acceleration was still feasible in vivo with negligible PI artifacts with lipid decontamination, thus decreasing the measurement time from 120 to 15 min for a 64 * 64 * 4 matrix. Magn Reson Med 78:429-440, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. PMID- 27548838 TI - Epigenetic-induced alterations in sex-ratios in response to climate change: An epigenetic trap? AB - We hypothesize that under the predicted scenario of climate change epigenetically mediated environmental sex determination could become an epigenetic trap. Epigenetically regulated environmental sex determination is a mechanism by which species can modulate their breeding strategies to accommodate environmental change. Growing evidence suggests that epigenetic mechanisms may play a key role in phenotypic plasticity and in the rapid adaptation of species to environmental change, through the capacity of organisms to maintain a non-genetic plastic memory of the environmental and ecological conditions experienced by their parents. However, inherited epigenetic variation could also be maladaptive, becoming an epigenetic trap. This is because environmental sex determination can alter sex ratios by increasing the survival of one of the sexes at the expense of negative fitness consequences for the other, which could lead not only to the collapse of natural populations, but also have an impact in farmed animal and plant species. PMID- 27548839 TI - Qigong/tai chi for sleep and fatigue in prostate cancer patients undergoing radiotherapy: a randomized controlled trial. AB - OBJECTIVES: Sleep disturbances and fatigue are common in prostate cancer patients undergoing radiotherapy. Prior research suggests mind-body techniques may improve these outcomes. We conducted a randomized controlled trial of qigong/tai chi (QGTC) in men with prostate cancer undergoing radiotherapy. METHODS: Men with prostate cancer starting definitive radiation were randomized to 1 of 3 groups: (1) QGTC; (2) light exercise (LE); or (3) waiting list control. Sleep disturbances (Pittsburgh Sleep Quality Index) and fatigue (Brief Fatigue Inventory) were assessed at baseline, midway through radiotherapy (T2), during the last week of radiotherapy (T3), and at 1 (T4) and 3 months (T5) after the end of radiotherapy. Patients in the QGTC and LE groups attended three 40-minute classes per week throughout radiotherapy. RESULTS: Ninety patients were randomized to the 3 groups (QGTC = 26; LE = 26; waiting list control = 24). The QGTC group reported longer sleep duration midway through radiotherapy (QGTC = 7.01 h; LE = 6.42; WL = 6.50; P = .05), but this difference did not persist over time. There were no group differences in other domains of sleep or fatigue. Exploratory analyses conducted to examine the effect of health-related quality of life (Expanded Prostate Cancer Index Composite and American Urological Association Symptom score) on sleep and fatigue showed significant correlations across multiple domains. CONCLUSIONS: Qigong/tai chi during radiation for prostate cancer resulted in superior sleep duration midway through radiation, but this effect was not durable, and there were no differences in other domains of sleep or fatigue. Exploratory analysis demonstrated that both sleep and fatigue were highly correlated with prostate cancer-related physical symptoms. Future mind-body intervention studies should incorporate multimodal therapy focused on improving physical symptoms in this population. PMID- 27548840 TI - Key components and potential benefits of a comprehensive approach to women's musculoskeletal health. AB - Over the last 40 years there has been a significant increase in the number of female athletes, as well as a rise in musculoskeletal injuries observed in women. There is sufficient evidence from past medical research identifying various musculoskeletal injuries and conditions that more commonly affect women, such as osteoarthritis, osteoporosis, stress fractures, and anterior cruciate ligament tears. Several women's sports medicine and musculoskeletal health programs have been developed throughout the United States in an attempt to provide more tailored care to the female athlete. The goal of a comprehensive approach to women's musculoskeletal health is to create an interdisciplinary team to facilitate treatment for a variety of injuries and related conditions. This manuscript outlines the musculoskeletal conditions that commonly affect women and highlights the various etiologies of these sex disparities. We discuss the role of interdisciplinary women's musculoskeletal health and sports medicine programs, and define the potential benefits of such an approach. Future studies should focus on assessing the outcomes of multidisciplinary women's sports medicine programs as current literature in this area is lacking. PMID- 27548841 TI - Predicting Risk of Ischemic or Bleeding Events After Percutaneous Coronary Intervention. PMID- 27548842 TI - Ondansetron in acute food protein-induced enterocolitis syndrome, a retrospective case-control study. AB - BACKGROUND: Therapy for moderate to severe acute food protein-induced enterocolitis syndrome (FPIES) typically consists of intravenous fluids and corticosteroids (traditional therapy). Ondansetron has been suggested as an adjunctive treatment. We aimed to evaluate the efficacy of the parenteral (intravenous or intramuscular) ondansetron vs traditional therapy to resolve the symptoms of acute FPIES. METHODS: Cases of FPIES who had a positive oral food challenge (OFC) were retrospectively examined at two major hospitals over a two year period (Rome, Italy; and Sydney, Australia). The efficacy of therapy, based on the percentage of cases who stopped vomiting, was compared in cases who received parenteral ondansetron and in cases who received traditional therapy or no pharmacological therapy. RESULTS: A total of 66 patients were included: 37 had parenteral ondansetron, 14 were treated with traditional therapy, and 15 did not receive any pharmacological therapy. Nineteen percentage of children treated with ondansetron continued vomiting after the administration of the therapy vs 93% of children who received traditional therapy (P < 0.05, relative risk = 0.2). Children who received ondansetron or no therapy were less likely to require an admission overnight compared with those who received traditional therapy (P < 0.05). CONCLUSIONS: Parenteral ondansetron is significantly more effective than traditional therapy in resolving acute symptoms of FPIES. The relative risk = 0.2 greatly reduces the bias linked to the lack of randomization. These findings suggest an effective treatment for vomiting in positive FPIES OFCs and allow for more confidence in performing OFCs. PMID- 27548844 TI - Professor Jules Traeger: A Giant in Nephrology and Transplantation. PMID- 27548843 TI - Patterns of Prescription Drug Use Before and After Fragility Fracture. AB - Importance: Patients who have a fragility fracture are at high risk for subsequent fractures. Prescription drugs represent 1 factor that could be modified to reduce the risk of subsequent fracture. Objective: To describe the use of prescription drugs associated with fracture risk before and after fragility fracture. Design, Setting, and Participants: Retrospective cohort study conducted between February 2015 and March 2016 using a 40% random sample of Medicare beneficiaries from 2007 through 2011 in general communities throughout the United States. A total of 168 133 community-dwelling Medicare beneficiaries who survived a fracture of the hip, shoulder, or wrist were included. Cohort members were required to be enrolled in fee-for-service Medicare with drug coverage (Parts A, B, and D) and to be community dwelling for at least 30 days in the immediate 4-month postfracture period. Exposures: Prescription drug use during the 4-month period before and after a fragility fracture. Main Outcomes and Measures: Prescription fills for drug classes associated with increased fracture risk were measured using Part D retail pharmacy claims. These were divided into 3 categories: drugs that increase fall risk; drugs that decrease bone density; and drugs with unclear fracture risk mechanism. Drugs that increase bone density were also tracked. Results: A total of 168 133 patients with a fragility fracture (141 569 women; 84.2%) met the inclusion criteria for this study; 91.8% were white. Across all fracture types, the mean (SD) age was 80.0 (7.7) years, and 53.2% of the fracture cohort was hospitalized at the time of the index fracture, although this varied significantly depending on fracture type (100% of hip fractures, 8.2% of wrist fractures, and 15.0% of shoulder fractures). The frequency of discharge to an institution for rehabilitation following hospitalization also varied by fracture type, but the mean (SD) duration of acute rehabilitation did not: 28.1 (19.8) days. Most patients were exposed to at least 1 nonopiate drug associated with increased fracture risk in the 4 months before fracture (77.1% of hip, 74.1% of wrist, and 75.9% of shoulder fractures). Approximately 7% of these patients discontinued this drug exposure after the fracture, but this was offset by new users after fracture. Consequently, the proportion of the cohort exposed following fracture was unchanged (80.5%, 74.3%, and 76.9% for hip, wrist, and shoulder, respectively). There was no change in the average number of fracture-associated drugs used. This same pattern of use before and after fracture was observed across all 3 drug mechanism categories. Use of drugs to strengthen bone density was uncommon (<=25%) both before and after fracture. Conclusions and Relevance: Exposure to prescription drugs associated with fracture risk is infrequently reduced following fragility fracture occurrence. While some patients eliminate their exposure to drugs associated with fracture, an equal number initiate new high risk drugs. This pattern suggests there is a missed opportunity to modify at least one factor contributing to secondary fractures. PMID- 27548845 TI - Six-Month Urinary CCL2 and CXCL10 Levels Predict Long-term Renal Allograft Outcome. AB - BACKGROUND: Early prognostic markers that identify high-risk patients could lead to increased surveillance, personalized immunosuppression, and improved long-term outcomes. The goal of this study was to validate 6-month urinary chemokine ligand 2 (CCL2) as a noninvasive predictor of long-term outcomes and compare it with 6 month urinary CXCL10. METHODS: A prospective, observational renal transplant cohort (n = 185; minimum, 5-year follow-up) was evaluated. The primary composite outcome included 1 or more: allograft loss, renal function decline (>20% decrease estimated glomerular filtration rate between 6 months and last follow-up), and biopsy-proven rejection after 6 months. CCL2/CXCL10 are reported in relation to urine creatinine (ng/mmol). RESULTS: Fifty-two patients (52/185, 28%) reached the primary outcome at a median 6.0 years, and their urinary CCL2:Cr was significantly higher compared with patients with stable allograft function (median [interquartile range], 38.6 ng/mmol [19.7-72.5] vs 25.9 ng/mmol [16.1 45.8], P = 0.009). Low urinary CCL2:Cr (<=70.0 ng/mmol) was associated with 88% 5 year event-free survival compared with 50% with high urinary CCL2:Cr (P < 0.0001). In a multivariate Cox-regression model, the only independent predictors of the primary outcome were high CCL2:Cr (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 1.33-5.73) and CXCL10:Cr (HR, 2.35; 95% CI, 1.23-4.88; both P = 0.009). Urinary CCL2:Cr/CXCL10:Cr area under the curves were 0.62 (P = 0.001)/0.63 (P = 0.03), respectively. Time-to-endpoint analysis according to combined high or low urinary chemokines demonstrates that endpoint-free survival depends on the overall early chemokine burden. CONCLUSIONS: This study confirms that urinary CCL2:Cr is an independent predictor of long-term allograft outcomes. Urinary CCL2:Cr/CXCL10:Cr alone have similar prognostic performance, but when both are elevated, this suggests a worse prognosis. Therefore, urinary chemokines may be a useful tool for timely identification of high-risk patients. PMID- 27548846 TI - Antithymocyte Globulin is Associated With a Lower Incidence of De Novo Donor Specific Antibodies in Moderately Sensitized Renal Transplant Recipients: Erratum. PMID- 27548847 TI - Targeted Antifungal Prophylaxis in Heart Transplant Recipients: Erratum. PMID- 27548848 TI - Prevalence and Risk Factors of Noncontrolled and Resistant Arterial Hypertension in Renal Transplant Recipients: Erratum. PMID- 27548849 TI - Longitudinal changes in CSF alpha-synuclein species reflect Parkinson's disease progression. AB - BACKGROUND: Parkinson's disease (PD) diagnosis is mainly based on clinical criteria, with a high risk of misdiagnosis. The identification of reliable biomarkers for disease diagnosis and progression has a key role for developing disease-modifying therapies. In this article, we investigated the longitudinal changes of CSF alpha-synuclein species in early PD patients and explored the potential use of these species as surrogate biomarkers for PD progression. METHODS: We used our newly developed enzyme-linked immunosorbent assay systems for measuring different forms of alpha-synuclein, such as oligomeric-alpha synuclein, phosphorylated-alpha-synuclein at serine 129, or total-alpha-synuclein in CSF from the longitudinal Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study cohort (n = 121). CSF Alzheimer's disease biomarkers (total tau, phosphorylated-tau, Abeta40 , and Abeta42 ) were also measured for this cohort. RESULTS: Interestingly, total-alpha-synuclein and oligomeric-alpha synuclein levels significantly increased during the 2-year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study follow-up period, whereas phosphorylated-alpha-synuclein at serine 129 levels showed a longitudinal decrease. We have also noted an association between a change of the oligomeric alpha-synuclein/total-alpha-synuclein ratio and a worsening of motor signs, in particular in the postural-instability and gait-difficulty dominant PD group. A strong positive correlation between the changes in CSF total-alpha-synuclein and oligomeric-alpha-synuclein during the 2-year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study was also noted (r = 0.84, P < .001). CONCLUSION: Our data show that CSF alpha-synuclein species have a dynamic pattern along the course of the disease, supporting their possible role as progression biomarkers for PD and their link with PD clinical phenotypes. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27548850 TI - Body Image, Food Addiction, Depression, and Body Mass Index in University Students. AB - The relationship between body image, depression, food addiction and body mass index (BMI) and differences in these variables due to gender and field of education have not been studied extensively. This study was conducted on a total of 793 university students (20.19 +/- 1.90 years). The Beck Depression Inventory, Yale Food Addiction, and Body Image Scale were used. It was determined that body image scores of females and individuals enrolled in health sciences programs were lower compared to those of males and those enrolled in the social sciences. There was a negative relationship between body image and depression and food addiction scores. There was a positive relationship between food addiction and depression scores, in addition to a positive relationship between food addiction and BMI. PMID- 27548853 TI - No P Please. PMID- 27548854 TI - Erratum. PMID- 27548855 TI - Client-Centered Advocacy: Every Occupational Therapy Practitioner's Responsibility to Understand Medical Necessity. AB - Occupational therapy practitioners must advocate for clients in multiple ways. The Occupational Therapy Practice Framework: Domain and Process as well as the Occupational Therapy Code of Ethics lend support to advocacy. Recognizing one's responsibility to provide advocacy for clients is different from knowing how to provide that advocacy. One aspect of health care affected by the Patient Protection and Affordable Care Act (ACA) is the definition and implementation of medical necessity. This article outlines some major concepts around medical necessity, particularly in relation to the passage of the ACA, and outlines guidance on how to advocate effectively to meet both individual and community needs. PMID- 27548856 TI - Promoting Health, Well-Being, and Quality of Life for Children Who Are Overweight or Obese and Their Families. AB - Obesity is a complex, multidimensional challenge that compromises occupational participation for children and families. Children who are overweight or obese are at serious risk for being stigmatized, bullied, or marginalized, and they often are medically compromised. They cope daily with occupational participation issues at home, in school, on playgrounds, and in their communities. Prevention and health promotion assessment and intervention in occupational therapy are imperative for the profession to make a significant and sustainable difference in the lives of these children and families. Innovative client- and occupation centered programming promotes health, well-being, and quality of life for this population. It is incumbent upon occupational therapy practitioners to prevent occupational marginalization, deprivation, and alienation while promoting occupational justice for children who are overweight or obese. PMID- 27548857 TI - Occupational Therapy Wellness Program: Youth and Parent Perspectives. AB - OBJECTIVE: In this study, we explored the impact of an occupational therapy wellness program on daily habits and routines through the perspectives of youth and their parents. METHOD: Data were collected through semistructured interviews with children and their parents, the Pizzi Healthy Weight Management Assessment((c)), and program activities. RESULTS: Three themes emerged from the interviews: Program Impact, Lessons Learned, and Time as a Barrier to Health. The most common areas that both youth and parents wanted to change were time spent watching television and play, fun, and leisure time. Analysis of activity pie charts indicated that the youth considerably increased active time in their daily routines from Week 1 to Week 6 of the program. CONCLUSION: An occupational therapy program focused on health and wellness may help youth and their parents be more mindful of their daily activities and make health behavior changes. PMID- 27548858 TI - Interventions to Promote Diabetes Self-Management in Children and Youth: A Scoping Review. AB - As children and youth with diabetes grow up, they become increasingly responsible for controlling and monitoring their condition. We conducted a scoping review to explore the research literature on self-management interventions for children and youth with diabetes. Eleven studies met the inclusion criteria. Some of the studies reviewed combined the participant population so that children with Type 1 as well as children with Type 2 diabetes were included. The majority of the studies focused on children age 14 yr or older and provided self-management education, self-management support, or both. Parent involvement was a key component of the majority of the interventions, and the use of technology was evident in 3 studies. The findings highlight factors that occupational therapy practitioners should consider when working with pediatric diabetes teams to select self-management interventions. PMID- 27548859 TI - Impact of a Child-Based Health Promotion Service-Learning Project on the Growth of Occupational Therapy Students. AB - This phenomenological study revealed the lived experiences of occupational therapy students as they embarked on a semester-long volunteer health promotion service-learning project during their entry-level master's program. Data analysis extrapolated themes from student journals, transcriptions of pre- and postinterviews, and field notes. Student roles were exemplified by what students wanted to learn, what they actually learned, and the unexpected benefits they experienced. In particular, issues with teaming, interprofessional development, and time management were discovered. The findings add to the growing literature about the benefits of service learning as a teaching strategy and how it facilitates mindfulness of community service, communication, and clinical reasoning of future therapists. Implications for learning and practice are discussed. PMID- 27548860 TI - Exploratory Study of the Clinical Utility of the Pizzi Healthy Weight Management Assessment (PHWMA) Among Burmese High School Students. AB - OBJECTIVE: Immigrant youth in the United States are at greater risk for weight management problems than non-Hispanic White youth. We used the Pizzi Healthy Weight Management Assessment (PHWMA) to capture data on health perceptions and weight management behaviors among adolescent Burmese refugees. METHOD: We conducted a retrospective descriptive study of 20 Burmese refugee high school students. RESULTS: The results captured an understanding of health perceptions and weight management behaviors of the program participants. The PHWMA was found to be a valid and reliable tool for use by occupational therapy practitioners. CONCLUSION: Findings from this study can inform program development and evaluation in outreach efforts to enhance minority youths' health and well-being. PMID- 27548861 TI - Health-Promoting Physical Activity of Children Who Use Assistive Mobility Devices: A Scoping Review. AB - Children with physical disabilities who use assistive mobility devices (AMDs) are at risk for obesity and other secondary health conditions. Habitual physical activity is one lifestyle factor that may prevent obesity and contribute to overall health, and an active lifestyle in childhood improves prospects for lifelong healthy behaviors. Child, family, and environmental facilitators and barriers influence health-promoting physical activity (HPPA) for children without disabilities, but comparable models and levels of understanding for children who use AMDs are lacking. In this scoping review, we identified a similar set of child, family, and environmental facilitators and barriers relevant to HPPA participation among children who use AMDs. Noted gaps in the literature included limited reporting of AMD use, inconsistent HPPA definitions, and inadequate measurement tools for children who are nonambulatory. The identified child, family, and environmental factors provide a framework for occupational therapy practitioners and interprofessional teams to develop HPPA opportunities and interventions for an underserved population. PMID- 27548862 TI - Relationship Between Physical Activity and Overweight and Obesity in Children: Findings From the 2012 National Health and Nutrition Examination Survey National Youth Fitness Survey. AB - OBJECTIVE: This study examined the relationship between childhood obesity and overweight and functional activity and its enjoyment. METHOD: A cross-sectional design was used to analyze data from the 2012 National Health and Nutrition Examination Survey National Youth Fitness Survey. Multivariate logistic regression models were used. RESULTS: Data for 1,640 children ages 3-15 yr were retrieved. Physical activity was negatively associated with risk of obesity (odds ratio [OR] = 0.93; 95% confidence interval [CI] [0.87, 0.98]). Although children who were obese and overweight were more likely to have functional limitations (ORs = 1.58-1.61), their enjoyment of physical activity participation was not significantly different from that of the healthy-weight group. CONCLUSION: Physical activity lowered the risk of obesity. Children who were obese had functional limitations compared with healthy-weight children, but both groups enjoyed physical activity equally. Future studies are needed to determine barriers to participation among these children in recreation and sporting activities. PMID- 27548863 TI - Sensory Patterns, Obesity, and Physical Activity Participation of Children With Autism Spectrum Disorder. AB - Obesity is a public health concern for the population in general and for children with autism spectrum disorder (ASD) specifically. The purpose of this study was to understand relationships between sensory patterns, obesity, and physical activity engagement of children with ASD (N = 77) sampled from a specialized community-based swimming program. This retrospective correlational study analyzed program data. Results show that almost half (42.2%) of the children were overweight or obese, and sensory avoiding behaviors were related to higher body mass index (BMI). Children participated in few formal and informal physically active recreation activities. Sensory seeking behaviors were associated with increased participation in informal activities, and higher BMI was associated with less participation in both formal and informal activities. Practitioners should consider sensory processing patterns and BMI when developing community based programs to promote physical activity of children with ASD. PMID- 27548864 TI - Benefits of a Culturally Tailored Health Promotion Program for Latino Youth With Disabilities and Their Families. AB - Little research is available about youth with disabilities, who experience numerous inequalities in health outcomes compared with youth without disabilities. Youth with disabilities experience many environmental and attitudinal barriers in maintaining healthy lifestyles, which put them at risk for obesity. Strong evidence has suggested that obesity rates are higher among youth with disabilities than among their nondisabled peers. The purpose of this study was to implement and examine the benefits of a culturally tailored healthy lifestyles program for Latino youth with disabilities and their families. Several cultural adaptations were made to align with the target population's cultural norms. Seventeen Latino families identified 67 behaviors they wanted to change or new habits they wanted to establish. The postassessment data showed that several family routines improved, and families reported engaging in many of the healthy habits they had identified for themselves. Implications of culturally appropriate and accessible programming are discussed. PMID- 27548865 TI - Effectiveness of a Sensory-Enriched Early Intervention Group Program for Children With Developmental Disabilities. AB - OBJECTIVE: The study's objective was to evaluate the effectiveness of the Interdisciplinary Sensory-Enriched Early Intervention (ISEEI) group program for children with developmental delays. METHOD: We conducted a retrospective chart review of 63 children ages 18-36 mo who participated in ISEEI. We evaluated participants with the Bayley Scales of Infant and Toddler Development III (Bayley III) and the Infant/Toddler Sensory Profile (ITSP) at enrollment and after 3-9 mo. We conducted a paired t test to examine changes in the Bayley-III between pre and posttests. RESULTS: At enrollment, 70% of children presented atypical scores in two or more areas of sensory processing in the ITSP. Results revealed that children with sensory processing difficulties demonstrated significant improvement in all areas of development except fine motor skills; children without sensory processing difficulties showed significant improvement in language and cognition. CONCLUSION: The ISEEI group program is an effective method to ameliorate developmental delays. PMID- 27548866 TI - Guided Imagery and Stress in Pregnant Adolescents. AB - OBJECTIVE: We examined the effects of a guided imagery intervention on perceived stress in pregnant adolescents. METHOD: Thirty-five pregnant adolescents recruited from a local alternative education program participated in a guided imagery intervention. Participants listened to a pregnancy-specific guided imagery recording on four separate occasions during their pregnancies. Perceived stress was measured immediately before and after each session using the Perceived Stress Measure-9 (PSM-9). RESULTS: Participants' pre- and postsession PSM-9 scores for three of the four sessions demonstrated a significant reduction in stress. Participants' baseline stress levels also decreased significantly across the four listening sessions. The greatest reductions in stress within and between sessions occurred in the early sessions, with effects diminishing over time. CONCLUSION: Pregnant teens experienced initial short- and long-term stress reduction during a guided imagery intervention, supporting the use of guided imagery to reduce stress in pregnant adolescents. PMID- 27548868 TI - Family-Centered Management of Sensory Challenges of Children With Autism: Single Case Experimental Design. AB - We explored the effectiveness of a sensory-based, family-centered coaching approach to changing problematic routines for young children with autism. Three mothers of young children with autism, atypical sensory processing, and global developmental delay each participated in a single-case experimental ABA design study. Mothers selected a problematic daily routine linked to sensory challenges as the focus of four intervention sessions provided in the home. Changes in mothers' perceptions of the children's behavior were the primary outcome, measured daily on a visual analog scale. Visual and descriptive analyses were undertaken. The sensory-based, family-centered coaching approach showed promise for changing sensory-related problem behaviors of young children with autism, but the degree and maintenance of the intervention effect varied among participants. PMID- 27548867 TI - Therapeutic Taping for Scapular Stabilization in Children With Brachial Plexus Birth Palsy. AB - OBJECTIVE: In this study, we aimed to assess whether therapeutic taping for scapular stabilization affected scapulothoracic, glenohumeral, and humerothoracic joint function in children with brachial plexus birth palsy and scapular winging. METHOD: Motion capture data were collected with and without therapeutic taping to assist the middle and lower trapezius in seven positions for 26 children. Data were compared with one-way multivariate analyses of variance. RESULTS: With therapeutic taping, scapular winging decreased considerably in all positions except abduction. Additionally, there were increased glenohumeral cross-body adduction and internal rotation angles in four positions. The only change in humerothoracic function was an increase of 3 degrees of external rotation in the external rotation position. CONCLUSION: Therapeutic taping for scapular stabilization resulted in a small but statistically significant decrease in scapular winging. Overall performance of positions was largely unchanged. The increased glenohumeral joint angles with therapeutic taping may be beneficial for joint development; however, the long-term impact remains unknown. PMID- 27548869 TI - Occupational Therapy Education Research: Results of a National Survey. AB - OBJECTIVE: Despite a strong tradition of education scholarship in occupational therapy, no systematic evaluation of the amount and nature of research in this arena, or its associated challenges, has been conducted. This study examined the scope and range of education-focused research conducted in Canada and identified perceived supports and barriers for this area of inquiry. METHOD: An online survey was sent to faculty of all 14 Canadian occupational therapy programs. Descriptive statistics were used to summarize areas of study focus, and qualitative thematic analysis captured respondents' perceptions of personal and environmental factors influencing their engagement in education research. RESULTS: Respondents (n = 47) reported engagement in education scholarship spanning more than 20 focus areas, often with limited resources. CONCLUSION: Strategies are proposed to promote the viability of education research in occupational therapy and to improve resources and other supports for this type of research. PMID- 27548870 TI - Social Participation in Schools: A Survey of Occupational Therapy Practitioners. AB - OBJECTIVE: We sought to identify strategies and practices that school-based occupational therapy practitioners use in addressing social participation, their perceptions of competence, and factors influencing their strategies and practices. METHOD: Surveys were sent to 500 randomly selected members of the American Occupational Therapy Association's Early Intervention and School Special Interest Section; 112 usable surveys were received from 36 states. RESULTS: Respondents reported focusing on internal client factors when addressing social participation. Fewer than half (46.5%) indicated that they understood their role (mean [M] = 4.23, standard deviation [SD] = 1.22), and 57.1% desired greater understanding or ability (M = 4.64, SD = 1.29). Differences were found based on years of experience, service delivery model used, and services provided by diagnosis category. CONCLUSION: School-based occupational therapy practitioners may need to expand their current practices in addressing student social participation. Findings may be used to develop interventions to address this area of practice. PMID- 27548871 TI - Interrater Reliability of the Revised Cognitive Performance Test (CPT): Assessing Cognition in People With Neurocognitive Disorders. AB - The rigor of occupation-based standardized assessments that rely on observational scoring procedures depends on proven reliability among test administrators. This study measured interrater reliability of the Cognitive Performance Test (CPT), a standardized, occupation-based assessment that measures cognitive-functional capacity in older adults with neurocognitive disorders. To capture a range of experience among test administrators, two sets of raters-four expert and three novice-scored video recordings of 10 patients administered the CPT. Interrater reliability results were strong among all raters (intraclass correlation coefficient [ICC] = .93), with expert raters (ICC = .97) yielding higher coefficients than novice raters (ICC = .93). Spearman's rho correlation coefficients were high among all raters (rs = .92-1.00). Practitioners can be confident that results of the CPT give accurate and consistent information to the health care team, family members, and patients when administered with fidelity using standardized protocols. PMID- 27548872 TI - Occupational Therapy Home Modification Assessment and Intervention. AB - Evidence Connection articles describe a clinical application of a systematic review developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice (EBP) Project. This Evidence Connection provides a case report of a client referred to occupational therapy for home modification assessment and intervention, applying the evidence from the systematic review of home modifications conducted in conjunction with the EBP Project. The client received in-home occupational therapy after side effects of liver disease resulted in increased falls within her home. PMID- 27548874 TI - Modified Primary Urethral Realignment Under Flexible Urethroscope. AB - OBJECTIVE: To assess the clinical significance of flexible endoscopic realignment in the treatment of posterior urethral disruption in comparison to the traditional open realignment method. METHODS: A total of 58 patients suffering posterior urethral disruption were enrolled into the current study from January 2003 to May 2009. Of them, 23 patients (Group A) were treated with modified technique of urethral realignment under flexible urethroscopy and 35 patients (Group B) received conventional open realignment. RESULTS: Either procedure was successfully performed in both groups. However, the operation time was significantly shorter in Group A (29.1 +/- 9.5 min) than that in Group B (58.1 +/ 11.2 min, p < 0.001). Also, patients in Group A had a significantly decreased incidence of stricture (4 of 23 cases in Group A versus 15 of 35 cases in Group B, p = 0.043) and formation of false urethra (0 of 23 cases in Group A versus 7 of 35 cases in Group B, p = 0.035). Prevalence of secondary urethroplasty was less in Group A (1/23) compared to Group B (8/35), but there was no statistical difference (p = 0.057). In addition, there was no significant difference in morbidity of urinary infection, incidence of incontinence, and impotence between the two groups (p > 0.05). CONCLUSION: Compared to the traditional open realignment, the new technique of urethral realignment under flexible endoscope has the advantage of short operation time, minimally invasive and less complications. PMID- 27548875 TI - The effects of music listening interventions on cognition and mood post-stroke: a systematic review. AB - INTRODUCTION: Music listening may have beneficial psychological effects but there has been no comprehensive synthesis of the available data describing efficacy of music listening in stroke. Areas covered: We performed a systematic review examining the effects of music listening interventions on cognition and mood post stroke. We found five published trials (n = 169 participants) and four ongoing trials. All studies demonstrated benefits of music listening on at least one measure of cognition or mood. Heterogeneity precluded meta-analysis and all included studies had potential risk of bias. Common reporting or methodological issues including lack of blinding, lack of detail on the intervention and safety reporting. Expert commentary: It is too early to recommend music listening as routine treatment post-stroke, available studies have been under-powered and at risk of bias. Accepting these caveats, music listening may have beneficial effects on both mood and cognition and we await the results of ongoing controlled studies. PMID- 27548876 TI - Why Cholesterol Testing in Children and Adolescents Matters. PMID- 27548877 TI - Radiographic Evaluation of Valvular Heart Disease With Computed Tomography and Magnetic Resonance Correlation. AB - Valvular heart disease is a group of complex entities with varying etiologies and clinical presentations. There are a number of imaging tools available to supplement clinical evaluation of suspected valvular heart disease, with echocardiography being the most common and clinically established, and more recent emergence of computed tomography and magnetic resonance imaging as additional supportive techniques. Yet even with these newer and more sophisticated modalities, chest radiography remains one of the earliest and most common diagnostic examinations performed during the triage of patients with suspected cardiac dysfunction. Recognizing the anatomic and pathologic features of cardiac radiography including the heart's adaptation to varying hemodynamic changes can provide clues to the radiologist regarding the underlying etiology. In this article, we will elucidate several principles relating to chamber modifications in response to pressure and volume overload as well as radiographic appearances associated with pulmonary fluid status and cardiac dysfunction. We will also present a pattern approach to optimize analysis of the chest radiograph for valvular heart disease, which will help guide the radiologist down a differential diagnostic pathway and create a more meaningful clinical report. PMID- 27548878 TI - Switching on electrocatalytic activity in solid oxide cells. AB - Solid oxide cells (SOCs) can operate with high efficiency in two ways-as fuel cells, oxidizing a fuel to produce electricity, and as electrolysis cells, electrolysing water to produce hydrogen and oxygen gases. Ideally, SOCs should perform well, be durable and be inexpensive, but there are often competitive tensions, meaning that, for example, performance is achieved at the expense of durability. SOCs consist of porous electrodes-the fuel and air electrodes separated by a dense electrolyte. In terms of the electrodes, the greatest challenge is to deliver high, long-lasting electrocatalytic activity while ensuring cost- and time-efficient manufacture. This has typically been achieved through lengthy and intricate ex situ procedures. These often require dedicated precursors and equipment; moreover, although the degradation of such electrodes associated with their reversible operation can be mitigated, they are susceptible to many other forms of degradation. An alternative is to grow appropriate electrode nanoarchitectures under operationally relevant conditions, for example, via redox exsolution. Here we describe the growth of a finely dispersed array of anchored metal nanoparticles on an oxide electrode through electrochemical poling of a SOC at 2 volts for a few seconds. These electrode structures perform well as both fuel cells and electrolysis cells (for example, at 900 degrees C they deliver 2 watts per square centimetre of power in humidified hydrogen gas, and a current of 2.75 amps per square centimetre at 1.3 volts in 50% water/nitrogen gas). The nanostructures and corresponding electrochemical activity do not degrade in 150 hours of testing. These results not only prove that in operando methods can yield emergent nanomaterials, which in turn deliver exceptional performance, but also offer proof of concept that electrolysis and fuel cells can be unified in a single, high-performance, versatile and easily manufactured device. This opens up the possibility of simple, almost instantaneous production of highly active nanostructures for reinvigorating SOCs during operation. PMID- 27548879 TI - Barriers to the Role of the Head Athletic Trainer for Women in National Collegiate Athletic Association Division II and III Settings. AB - CONTEXT: Very few women assume the role of head athletic trainer (AT). Reasons for this disparity include discrimination, motherhood, and a lack of interest in the position. However, data suggest that more women seek the head AT position in National Collegiate Athletic Association Division II and III settings. OBJECTIVE: To examine the barriers female ATs face as they transition to the role of head AT. DESIGN: Qualitative study. SETTING: Divisions II and III. PATIENTS OR OTHER PARTICIPANTS: In total, 77 female ATs participated in our study. Our participants (38 +/- 9 years old) were employed as head ATs at the Division II or III level. DATA COLLECTION AND ANALYSIS: We conducted online interviews with all participants. They journaled their reflections to a series of open-ended questions pertaining to their experiences as head ATs. Data were analyzed following a general inductive approach. Credibility was secured by peer review and researcher triangulation. RESULTS: Organizational and personal factors emerged as the 2 major themes that described challenges for women assuming the role of the head AT. Organizational barriers were defined by gender stereotyping and the "good old boys" network. Personal influences included a lack of leadership aspirations, motherhood and family, and a lack of mentors. CONCLUSIONS: Female ATs working in Divisions II or III experienced similar barriers to assuming the role of the head AT as those working in the Division I setting. Stereotyping still exists within collegiate athletics, which limits the number of women in higher-ranking positions; however, a lack of desire to assume a higher position and the desire to balance work and home inhibit some women from moving up. PMID- 27548880 TI - Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder. AB - Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto-striato-thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting-state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small-world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109-119, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27548881 TI - The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery. AB - INTRODUCTION: The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic. PMID- 27548882 TI - European Expert Consensus Paper on the implementation of Article 14 of the WHO Framework Convention on Tobacco Control. AB - On 24 November 2015, under the auspices of the European Policy Roundtable on Smoking Cessation, 15 experts on tobacco control and dependence from across the European Union, chaired by Professor Luke Clancy, met in Oslo, Norway, to discuss the implementation of the Tobacco Products Directive and the WHO Framework Convention on Tobacco Control, namely Article 14. On the occasion of the 10th anniversary of the Framework Convention on Tobacco Control, this paper reports the consensus reached by all Roundtable participants on the need to further advance the availability and access to services to support cessation of tobacco use. The implementation of services to support cessation of tobacco use in line with Article 14 can and should be significantly improved to protect the health of European citizens. The meeting was initiated and funded by Pfizer. PMID- 27548883 TI - Reply to letter: Nonmotor symptoms in subjects without evidence of dopaminergic deficits. PMID- 27548884 TI - Bilateral Anterior Knee Pain in a High School Cross-Country Runner: An Atypical Etiology. AB - Anterior knee pain is a common complaint found in distance runners, and can be the end result of a variety of benign processes. A 17-year-old female cross country runner presented to a sports medicine clinic with insidious onset of bilateral patellofemoral pain (PFP). In the workup of the significant quadriceps weakness discovered on her initial examination, a principal contributing cause of her PFP, she was found to have a form of spinal muscular atrophy, an uncommon neurodegenerative disease that typically requires multidisciplinary medical care. Her case provides a good example for clinicians to consider, at times, an in depth assessment of the root causes of benign conditions. PMID- 27548885 TI - Performance measures for upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. PMID- 27548886 TI - The effect of dietary intake of coenzyme Q10 on skin parameters and condition: Results of a randomised, placebo-controlled, double-blind study. AB - Coenzyme Q10 (CoQ10) is a natural constituent of foods and is also often used in both functional foods and supplements. In addition, it is a common ingredient of cosmetics where it is believed to reduce the signs of skin ageing. However, the existing data about the effect of dietary intake of CoQ10 on skin parameters and condition are scarce. To gain an insight into this issue, we conducted a double blind, placebo-controlled experiment with 33 healthy subjects. Our objective was to investigate the effects of 12 weeks of daily supplementation with 50 and 150 mg of CoQ10 on skin parameters and condition. Study was conducted with a water soluble form of CoQ10 with superior bioavailability (Q10Vital(r) ). While the results of some previous in vitro studies showed possible protection in UVB response, we did not observe significant changes in the minimal erythema dose (MED). On the other hand, the intake of CoQ10 limited seasonal deterioration of viscoelasticity and reduced some visible signs of ageing. We determined significantly reduced wrinkles and microrelief lines, and improved skin smoothness. Supplementation with CoQ10 did not significantly affect skin hydration and dermis thickness. (c) 2016 BioFactors, 43(1):132-140, 2017. PMID- 27548887 TI - Bacteriuria increases the risk of edematous attacks in hereditary angioedema with C1-inhibitor deficiency. AB - Urinary tract infections are considered among the most common infectious disorders in humans. Various infections may have a role in inducing HAE attacks. Our study intended to evaluate bacteriuria in the urinalysis of patients with C1 INH-HAE. Urine specimens contributed by 139 patients with C1-INH-HAE at the annual control visits were studied retrospectively for microorganisms. We analyzed the presence of bacteriuria in relation to the clinical symptoms. Taking into account three randomly selected urine specimens, we found that the cumulative number of edematous attacks was higher in patients with bacteriuria than in those without (P = 0.019, P = 0.022, P = 0.014). Considering the same patients, attack number was significantly higher (14.51 vs 8.63) in patients with bacteriuria than in those without (P < 0.0001). In patients with bacteriuria, we found a higher incidence of edema formation during the year before evaluation, which may suggest the triggering role of bacteriuria in the occurrence of edematous episodes. PMID- 27548888 TI - Intraocular Pressure Changes and Relationship With Corneal Biomechanics After SMILE and FS-LASIK. AB - PURPOSE: The purpose of this article was to evaluate intraocular pressure (IOP) changes and investigate the relationship with corneal biomechanics after small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). METHODS: A total of 193 eyes of 193 patients who underwent SMILE and FS-LASIK procedures were included in this retrospective study. Data were collected preoperatively and postoperatively, including Goldmann correlated IOP (IOPg), corneal-compensated IOP (IOPcc), corneal hysteresis (CH), and corneal resistance factor (CRF) by ocular response analyzer, noncontact intraocular pressure (IOPNCT) by noncontact tonometer, and Ehlers, Shah, Dresden, Kohlhaas, Orssengo/Pye by the Pentacam corrected system. Changes in both groups and differences between groups were evaluated. Multiple linear regression models were constructed to explore factors influencing IOP changes. RESULTS: In SMILE, the IOPg, IOPcc, IOPNCT, and Kohlhaas decreased significantly at 1 month postoperatively (P < 0.01), whereas with the Ehlers formula they significantly increased (P < 0.01). IOPs decreased at 3 and 6 months compared with all preoperative values except Ehlers values (P < 0.01), but there was no significant difference between 3 and 6 months (P > 0.05). In FS-LASIK, the IOPg, IOPcc, and IOPNCT decreased significantly at 1 month (P < 0.01), whereas in the Ehlers and Shah formulas they significantly increased (P < 0.01). Compared with preoperative values, the IOPs decreased at 3 and 6 months except in the Ehlers and Shah formulas (P < 0.01). Only IOPg and IOPcc differed between 3 and 6 months (P < 0.05). The Ehlers and Shah formulas were closer to the preoperative IOP for both groups, with variation approximately 1 mm Hg at 6 months postoperatively. Preoperative IOP, postoperative corneal resistance factor, corneal hysteresis, and flat keratometry were enrolled into the regression equations. CONCLUSIONS: IOP underestimation after SMILE or FS-LASIK was related to corneal biomechanics as well as preoperative IOP and flat keratometry. IOP after SMILE seem to remain more stable. Accordingly, the Ehlers and Shah formulas were closer to the preoperative IOP. It may be useful to estimate future IOP with the best-fit models after surgery. PMID- 27548889 TI - Intereye Difference in the Microstructure of Parapapillary Atrophy in Unilateral Primary Open-Angle Glaucoma. AB - PURPOSE: To investigate intereye differences in the parapapillary atrophy (PPA) microstructure in unilateral primary open-angle glaucoma (POAG). METHODS: Bilateral optic nerves from 172 unilateral POAG patients having clinical PPA shown in infrared fundus imaging were scanned using spectral-domain optical coherence tomography (SD-OCT). Based on the extent of Bruch's membrane (BM) within the PPA area, the PPA was divided into beta-zone (area with BM) and gamma zone (area devoid of BM). The width of each type of PPA and disc tilt angle were measured in radial B-scan images. Disc tilt ratio and torsion degree were determined using the radial B-scan and infrared fundus images. Measurements were compared between the glaucomatous and contralateral healthy eyes, and the factors associated with the presence of glaucoma were determined. RESULTS: The width of beta-zone was larger in glaucomatous eyes compared with the contralateral healthy eyes (283.67 +/- 157.45 vs. 214.42 +/- 145.39 MUm, P < 0.001), whereas there were no significant intereye differences in the gamma-zone width (P = 0.392). Eyes with POAG had a larger beta-zone width (P < 0.001), and larger tilt angle (P = 0.032) compared with the contralateral healthy eyes. In multivariate regression analysis, larger beta-zone width (P < 0.001), and lower IOP (P = 0.001) were revealed as significant factors associated with the presence of glaucoma. CONCLUSIONS: The beta-zone width was revealed as a significant lateralizing factor for unilateral POAG, whereas the gamma-zone was not associated with the presence of glaucoma. PMID- 27548890 TI - Glaucoma Diagnostic Ability of the New Circumpapillary Retinal Nerve Fiber Layer Thickness Analysis Based on Bruch's Membrane Opening. AB - PURPOSE: To compare the diagnostic ability of the new spectral-domain optical coherence tomography (SD-OCT) algorithm for measuring circumpapillary retinal nerve fiber layer (RNFL) thickness centered on Bruch's membrane opening (BMO), with the conventional circumpapillary RNFL thickness measurement centered on the optic disc. METHODS: In 75 eyes with primary open-angle glaucoma (POAG) and 71 healthy control eyes, circumpapillary RNFL thickness was measured with SD-OCT, first by centering the scan circle on the optic disc (RNFLDi), and then on the BMO (RNFLBMO). Difference between the topographic profiles of RNFLDi and RNFLBMO was compared and factors influencing any discrepancies between methods were investigated. Glaucoma diagnostic abilities of each method were assessed using the areas under receiver operating characteristic curve (AUCs). RESULTS: Axial length did not differ between POAG and healthy eyes. A longer axial length and larger width of externally oblique border tissue (BT) associated with tilted optic disc were the two major factors influencing discrepancies between RNFLBMO and RNFLDi (both P < 0.001). Compared with RNFLBMO, RNFLDi tended to result in a thinner nasal RNFL in eyes with externally oblique BT, while RNFLBMO and RNFLDi were comparable in eyes without externally oblique BT. The glaucoma diagnostic capabilities were generally comparable, but RNFLBMO was superior to RNFLDi in eyes having a larger width (>250 MUm) of externally oblique BT (AUC = 0.933 vs. 0.843, respectively, P = 0.027). CONCLUSIONS: The new circumpapillary RNFL scanning algorithm centered on BMO may provide a more reliable RNFL profile in eyes with tilted optic discs, with a largely comparable glaucoma diagnostic ability to the conventional algorithm. PMID- 27548892 TI - Erratum. PMID- 27548891 TI - MicroRNA Expression Profile in Conjunctival Melanoma. AB - PURPOSE: Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and prognostic microRNA (miRNA) in CM and to compare the miRNA profile with that of MM. METHODS: Using microarray analysis (Affymetrix) we determined the miRNA expression profile in 40 CMs compared with 7 normal conjunctival samples. Changes in miRNA expression were associated with T stage, local recurrence, metastasis, and mortality. Furthermore, the expression of six fresh frozen tissue samples of CM was compared with that of four laryngeal and sinonasal MM. RESULTS: Our analysis revealed 24 upregulated and 1 downregulated miRNA in CM; several of these miRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated miRNAs specific for stage T1 and stage-T2 CM, whose expression was associated with increased tumor thickness (P = 0.007), and two upregulated miRNAs (miR-3687 and miR-3916) associated with an increased risk of local recurrence. No stage T3-specific miRNAs were identified. CONCLUSIONS: We identified differentially expressed and potentially prognostic miRNAs in CM. Furthermore, the miRNA expression pattern of CM resembled that in MM. The identification of these differentially expressed miRNAs provides an entry point for future functional studies of miRNAs as prognostic or therapeutic targets in CM and highlights the resemblance between CM, MM, and cutaneous melanoma. PMID- 27548893 TI - Concerning Manuscript "Deficient Binocular Combination of Second-Order Stimuli in Amblyopia". PMID- 27548894 TI - Author Response: Concerning Manuscript "Deficient Binocular Combination of Second Order Stimuli in Amblyopia". PMID- 27548895 TI - Perceptual Learning in Children With Infantile Nystagmus: Effects on Visual Performance. AB - PURPOSE: To evaluate whether computerized training with a crowded or uncrowded letter-discrimination task reduces visual impairment (VI) in 6- to 11-year-old children with infantile nystagmus (IN) who suffer from increased foveal crowding, reduced visual acuity, and reduced stereopsis. METHODS: Thirty-six children with IN were included. Eighteen had idiopathic IN and 18 had oculocutaneous albinism. These children were divided in two training groups matched on age and diagnosis: a crowded training group (n = 18) and an uncrowded training group (n = 18). Training occurred two times per week during 5 weeks (3500 trials per training). Eleven age-matched children with normal vision were included to assess baseline differences in task performance and test-retest learning. Main outcome measures were task-specific performance, distance and near visual acuity (DVA and NVA), intensity and extent of (foveal) crowding at 5 m and 40 cm, and stereopsis. RESULTS: Training resulted in task-specific improvements. Both training groups also showed uncrowded and crowded DVA improvements (0.10 +/- 0.02 and 0.11 +/- 0.02 logMAR) and improved stereopsis (670 +/- 249"). Crowded NVA improved only in the crowded training group (0.15 +/- 0.02 logMAR), which was also the only group showing a reduction in near crowding intensity (0.08 +/- 0.03 logMAR). Effects were not due to test-retest learning. CONCLUSIONS: Perceptual learning with or without distractors reduces the extent of crowding and improves visual acuity in children with IN. Training with distractors improves near vision more than training with single optotypes. Perceptual learning also transfers to DVA and NVA under uncrowded and crowded conditions and even stereopsis. Learning curves indicated that improvements may be larger after longer training. PMID- 27548896 TI - Perceptual Learning in Children With Infantile Nystagmus: Effects on 2D Oculomotor Behavior. AB - PURPOSE: To determine changes in oculomotor behavior after 10 sessions of perceptual learning on a letter discrimination task in children with infantile nystagmus (IN). METHODS: Children with IN (18 children with idiopathic IN and 18 with oculocutaneous albinism accompanied by IN) aged 6 to 11 years were divided into two training groups matched on diagnosis: an uncrowded training group (n = 18) and a crowded training group (n = 18). Target letters always appeared briefly (500 ms) at an eccentric location, forcing subjects to quickly redirect their gaze. Training occurred twice per week for 5 consecutive weeks (3500 trials total). Norm data and test-retest values were collected from children with normal vision (n = 11). Outcome measures were: nystagmus characteristics (amplitude, frequency, intensity, and the expanded nystagmus acuity function); fixation stability (the bivariate contour ellipse area and foveation time); and saccadic eye movements (latencies and accuracy) made during a simple saccade task and a crowded letter-identification task. RESULTS: After training, saccadic responses of children with IN improved on the saccade task (latencies decreased by 14 +/- 4 ms and gains increased by 0.03 +/- 0.01), but not on the crowded letter task. There were also no training-induced changes in nystagmus characteristics and fixation stability. Although children with normal vision had shorter latencies in the saccade task (47 +/- 14 ms at baseline), test-retest changes in their saccade gains and latencies were almost equal to the training effects observed in children with IN. CONCLUSIONS: Our results suggest that the improvement in visual performance after perceptual learning in children with IN is primarily due to improved sensory processing rather than improved two-dimensional oculomotor behavior. PMID- 27548897 TI - Perceptual Learning in Children With Infantile Nystagmus: Effects on Reading Performance. AB - PURPOSE: Perceptual learning improves visual acuity and reduces crowding in children with infantile nystagmus (IN). Here, we compare reading performance of 6 to 11-year-old children with IN with normal controls, and evaluate whether perceptual learning improves their reading. METHODS: Children with IN were divided in two training groups: a crowded training group (n = 18; albinism: n = 8; idiopathic IN: n = 10) and an uncrowded training group (n = 17; albinism: n = 9; idiopathic IN: n = 8). Also 11 children with normal vision participated. Outcome measures were: reading acuity (the smallest readable font size), maximum reading speed, critical print size (font size below which reading is suboptimal), and acuity reserve (difference between reading acuity and critical print size). We used multiple regression analyses to test if these reading parameters were related to the children's uncrowded distance acuity and/or crowding scores. RESULTS: Reading acuity and critical print size were 0.65 +/- 0.04 and 0.69 +/- 0.08 log units larger for children with IN than for children with normal vision. Maximum reading speed and acuity reserve did not differ between these groups. After training, reading acuity improved by 0.12 +/- 0.02 logMAR and critical print size improved by 0.11 +/- 0.04 logMAR in both IN training groups. The changes in reading acuity, critical print size, and acuity reserve of children with IN were tightly related to changes in their uncrowded distance acuity and the changes in magnitude and extent of crowding. CONCLUSIONS: Our findings are the first to show that visual acuity is not the only factor that restricts reading in children with IN, but that crowding also limits their reading performance. By targeting both of these spatial bottlenecks in children with IN, our perceptual learning paradigms significantly improved their reading acuity and critical print size. This shows that perceptual learning can effectively transfer to reading. PMID- 27548898 TI - Depression in Visual Impairment Trial (DEPVIT): A Randomized Clinical Trial of Depression Treatments in People With Low Vision. AB - PURPOSE: The purpose of this study was to compare two interventions for depression, problem solving treatment (PST) and referral to the patient's physician, with a waiting-list control group in people with sight loss and depressive symptoms. METHODS: This was an assessor-masked, exploratory, multicenter, randomized clinical trial, with concurrent economic analysis. Of 1008 consecutive attendees at 14 low-vision rehabilitation centers in Britain, 43% (n = 430) screened positive for depressive symptoms on the Geriatric Depression Scale and 85 of these attendees participated in the trial. Eligible participants were randomized in the ratio 1:1:1 to PST, referral to their physician, or a waiting-list control arm. PST is a manualized talking intervention delivered by a trained therapist who teaches people over six to eight sessions to implement a seven-step method for solving their problems. Referral to the physician involved sending a referral letter to the person's physician, encouraging him or her to consider treatment according to the stepped care protocol recommended by the U.K.'s National Institute of Health and Care Excellence. The primary outcome was change in depressive symptoms (6 months after baseline) as determined by the Beck Depression Inventory. RESULTS: At 6 months, Beck Depression Inventory scores reduced by 1.05 (SD 8.85), 2.11 (SD 7.60), and 2.68 (SD 7.93) in the waiting-list control, referral, and PST arms, respectively. The cost per patient of the PST intervention was L1176 in Wales and L1296 in London. CONCLUSIONS: Depressive symptoms improved most in the PST group and least in the control group. However, the change was small and the uncertainty of the measurements relatively large. PMID- 27548899 TI - Identification of Novel Mutations in the LRR-Cap Domain of C21orf2 in Japanese Patients With Retinitis Pigmentosa and Cone-Rod Dystrophy. AB - PURPOSE: C21orf2 encodes a ciliary protein related to syndromic and nonsyndromic retinal degeneration. The purpose of this study was to identify novel mutations of C21orf2 associated with syndromic autosomal recessive retinitis pigmentosa (arRP) and autosomal recessive cone-rod dystrophy (arCRD) by using whole exome sequencing of a Japanese cohort. METHODS: Whole exome sequencing was performed on DNA from affected and healthy members from 147 families with retinal degenerations. Identified nonsense and missense mutations were further restricted by using the reported single nucleotide variation frequencies and inherited patterns. The effect of the mutations was examined by in vitro assays. RESULTS: Novel mutations in C21orf2 were found in Japanese patients with arRP with skeletal defects or arCRD. Compound heterozygous mutations, from one family (p.V111M and p.Y107H), and a homozygous mutation, from another family (p.Y107C), were all located in the leucine-rich repeat C-terminal domain required for protein stabilization. C21orf2 was expressed in the retina through the developing to the mature stage, and the protein localized to the photoreceptor cilia in the adult retina. In vitro expression showed reduced levels and affected localizations of mutated protein products compared to the wild type. CONCLUSIONS: The identified C21orf2 mutations decreased protein stability and affected cytoplasmic localization of C21orf2. Since C21orf2 was required for ciliogenesis, our data suggested that reduced levels of functional C21orf2 induced photoreceptor degradation through abnormal cilia formation, leading to arRP or arCRD in the retina. PMID- 27548900 TI - Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes. AB - PURPOSE: Recent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce inflammatory changes in nearby cells. METHODS: Laser capture microdissection was used to isolate the outer retina (photoreceptors) from the inner retina in nondiabetic and diabetic mice. Diabetes-induced changes in the expression of inflammatory targets were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. Cell culture experiments were carried out to determine if photoreceptors in vitro and ex vivo release soluble mediators that can stimulate nearby cells. Photoreceptor contribution to leukocyte-mediated endothelial cell death was tested using coculture models. RESULTS: Messenger ribonucleic acid and protein expression levels for inflammatory proteins intercellular adhesion molecule 1 (ICAM1), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) were increased in photoreceptors cells in diabetes. In vitro and ex vivo studies show that photoreceptor cells in elevated glucose release mediators that can induce tumor necrosis factor-alpha in leukocytes and endothelial cells, but not in glia. The soluble mediators released by photoreceptor cells in elevated glucose are regulated by transforming growth factor beta-activated kinase 1 and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling. In contrast to enhanced leukocyte-mediated killing of endothelial cells by leukocytes from wild type diabetic mice, leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill endothelial cells. CONCLUSIONS: These data indicate that photoreceptor cells are a source of inflammatory proteins in diabetes, and their release of soluble mediators can contribute to the death of retinal capillaries in diabetes. PMID- 27548901 TI - Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes. AB - PURPOSE: Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin-/- and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. METHODS: Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. RESULTS: Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. CONCLUSIONS: Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID- 27548902 TI - Association Between Aqueous Flare and Epiretinal Membrane in Retinitis Pigmentosa. AB - PURPOSE: Epiretinal membrane (ERM) is a frequent macular complication in patients with retinitis pigmentosa (RP). The etiology of ERM formation in RP is largely unknown. The purpose of this study was to investigate the association between aqueous flare, a surrogate index of intraocular inflammation, and ERM secondary to RP. METHODS: We retrospectively studied a total of 206 eyes of 117 patients who were diagnosed with typical RP. Aqueous flare values were measured consecutively in 2012 and 2013 using a laser flare cell meter. Spectral-domain optical coherence tomography images and fundus photographs taken on the same day of the aqueous flare measurements were analyzed for ERM detection. RESULTS: The mean values of aqueous flare, age, and frequency of male sex were significantly higher in the RP patients with ERM compared with the RP patients without ERM (P < 0.0001, P = 0.007, and P = 0.004, respectively). After adjustment for age and sex, the eyes in the highest quartile of aqueous flare had significantly higher odds of having ERM than those in the lowest quartile (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.04-6.93), and the linear trend across flare levels was significant (P = 0.005). In addition, each 1-log-transformed increase in flare values was associated with an elevation of the likelihood of having ERM (OR, 2.59; 95% CI, 1.33-5.06). CONCLUSIONS: Our analysis demonstrated that elevated aqueous flare is associated with ERM secondary to RP, suggesting that inflammation may be implicated in the pathogenesis of ERM formation in RP. PMID- 27548903 TI - Lessons to Be Learned From the UK Junior Doctors' Strike. PMID- 27548904 TI - Click Synthesis, Aggregation-Induced Emission and Chirality, Circularly Polarized Luminescence, and Helical Self-Assembly of a Leucine-Containing Silole. AB - By introducing chiral leucine pendants to silole scaffold, leucine-containing silole (Silole-Leu) is synthesized and it is endowed with not only aggregation induced emission and circular dichroism, but excellent chiral polarized luminescence as well. Silole-Leu also has the capacity to self-assemble into nano/micro helical luminescent fibers and the dimension of the fibers can be tuned by adjusting the ratio and volume of mixed solvents for evaporation as revealed by atomic force microscope, scanning electron microscope, and fluorescence microscope. The characteristic helicity of microfibers is directly visualized for the first time by using fluorescence microscope. PMID- 27548905 TI - Medial Longitudinal Arch Angle Presents Significant Differences Between Foot Types: A Biplane Fluoroscopy Study. AB - The structure of the medial longitudinal arch (MLA) affects the foot's overall function and its ability to dissipate plantar pressure forces. Previous research on the MLA includes measuring the calcaneal-first metatarsal angle using a static sagittal plane radiograph, a dynamic height-to-length ratio using marker clusters with a multisegment foot model, and a contained angle using single point markers with a multisegment foot model. The objective of this study was to use biplane fluoroscopy to measure a contained MLA angle between foot types: pes planus (low arch), pes cavus (high arch), and normal arch. Fifteen participants completed the study, five from each foot type. Markerless fluoroscopic radiostereometric analysis (fRSA) was used with a three-dimensional model of the foot bones and manually matching those bones to a pair of two-dimensional radiographic images during midstance of gait. Statistically significant differences were found between barefoot arch angles of the normal and pes cavus foot types (p = 0.036), as well as between the pes cavus and pes planus foot types (p = 0.004). Dynamic walking also resulted in a statistically significant finding compared to the static standing trials (p = 0.014). These results support the classification of individuals following a physical assessment by a foot specialist for those with pes cavus and planus foot types. The differences between static and dynamic kinematic measurements were also supported using this novel method. PMID- 27548906 TI - Infection-induced behavioural changes reduce connectivity and the potential for disease spread in wild mice contact networks. AB - Infection may modify the behaviour of the host and of its conspecifics in a group, potentially altering social connectivity. Because many infectious diseases are transmitted through social contact, social connectivity changes can impact transmission dynamics. Previous approaches to understanding disease transmission dynamics in wild populations were limited in their ability to disentangle different factors that determine the outcome of disease outbreaks. Here we ask how social connectivity is affected by infection and how this relationship impacts disease transmission dynamics. We experimentally manipulated disease status of wild house mice using an immune challenge and monitored social interactions within this free-living population before and after manipulation using automated tracking. The immune-challenged animals showed reduced connectivity to their social groups, which happened as a function of their own behaviour, rather than through conspecific avoidance. We incorporated these disease-induced changes of social connectivity among individuals into models of disease outbreaks over the empirically-derived networks. The models revealed that changes in host behaviour frequently resulted in the disease being contained to very few animals, as opposed to becoming widespread. Our results highlight the importance of considering the role that behavioural alterations during infection can have on social dynamics when evaluating the potential for disease outbreaks. PMID- 27548907 TI - Cell-Mediated Proteolytic Release of Growth Factors from Poly(Ethylene Glycol) Matrices. AB - Engineering in vitro tissue mimetics that resemble the corresponding living tissues requires the 3D arrangement of tissue progenitor cells and their differentiation by localized growth factor (GF) signaling cues. Recent technological advances open a large field of possibilities for the creation of complex GF arrangements. Additionally, cell-instructive biomaterials, which bind GFs by various mechanisms and release them with different kinetics depending on binding affinity, have become available. This paper describes the development of a matrix metalloproteinase (MMP)-degradable streptavidin-based linker module, which allows the release of immobilized GFs from synthetic biomimetic poly(ethylene glycol) hydrogels independently of the hydrogel degradation. The MMP-sensitive streptavidin linker is shown to efficiently bind biotinylated molecules, and as proof of concept, bone morphogenetic protein-2 (BMP-2) delivery via the MMP-degradable linker is used to induce osteogenic differentiation in C2C12 cells and mesenchymal stem cells. The results show a significantly increased net effect of proteolytically releasable BMP-2 in comparison to stably immobilized and soluble BMP-2. This study indicates that a GF delivery system directly responsive to cellular activity can have important implications for the synthesis of tissue mimetics and regenerative medicine, as it can influence the availability, the localization of effects, as well as efficacy of employed GFs. PMID- 27548908 TI - Support stance in carers of adults with eating disorders: Factors associated with collaborative versus directive approaches. AB - : The support provided by family and friends is integral to patient motivation and clinical outcomes across health care populations. However, little is known about factors that promote or interfere with the type of support offered. OBJECTIVE: This research examined factors associated with collaborative versus directive support among carers of adults with eating disorders. METHOD: Participants were mothers, fathers, partners, friends, and siblings (N = 141) of eating disorder patients in hospital or residential treatment. Two methodologies were used to assess directive and collaborative support stance: a questionnaire of support behaviors and coded responses to clinical vignettes. Measures of interpersonal functioning, psychiatric distress, caregiving experience, and closeness with their loved one were also completed. RESULTS: Although carers rated a collaborative stance as more helpful than a directive stance, 60% of responses to the clinical vignettes were directive. Across both methodologies, collaborative support behaviors were associated with beliefs about helpful support and with a less vindictive and cold interpersonal style. Whereas use of a directive support stance was exclusively associated with negative caregiving experiences, collaborative responses were associated with both positive and negative experiences. DISCUSSION: Although the benefits of collaborative support have been well established, this is the first study to examine factors associated with the use of support stance. Findings suggest a number of ways to help carers create and maintain collaborative relationships, including addressing beliefs and interpersonal style and capitalizing on both positive and negative experiences with their loved one. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:498-505). PMID- 27548909 TI - Association between glycaemic control and common infections in people with Type 2 diabetes: a cohort study. AB - AIM: To investigate the impact of glycaemic control on infection incidence in people with Type 2 diabetes. METHODS: We compared infection rates during 2014 in people with Type 2 diabetes and people without diabetes in a large primary care cohort in the UK (the Royal College of General Practitioners Research and Surveillance Centre database). We performed multilevel logistic regression to investigate the impact of Type 2 diabetes on presentation with infection, and the effect of glycaemic control on presentation with upper respiratory tract infections, bronchitis, influenza-like illness, pneumonia, intestinal infectious diseases, herpes simplex, skin and soft tissue infections, urinary tract infections, and genital and perineal infections. People with Type 2 diabetes were stratified by good [HbA1c < 53 mmol/mol (< 7%)], moderate [HbA1c 53-69 mmol/mol (7-8.5%)] and poor [HbA1c > 69 mmol/mol (> 8.5%)] glycaemic control using their most recent HbA1c concentration. Infection incidence was adjusted for important sociodemographic factors and patient comorbidities. RESULTS: We identified 34 278 people with Type 2 diabetes and 613 052 people without diabetes for comparison. The incidence of infections was higher in people with Type 2 diabetes for all infections except herpes simplex. Worsening glycaemic control was associated with increased incidence of bronchitis, pneumonia, skin and soft tissue infections, urinary tract infections, and genital and perineal infections, but not with upper respiratory tract infections, influenza-like illness, intestinal infectious diseases or herpes simplex. CONCLUSIONS: Almost all infections analysed were more common in people with Type 2 diabetes. Infections that are most commonly of bacterial, fungal or yeast origin were more frequent in people with worse glycaemic control. PMID- 27548910 TI - Is Neuromuscular Blocker Necessary in Pediatric Patients Undergoing Laparoscopic Inguinal Hernia Repair with Percutaneous Internal Ring Suturing? AB - Purpose The aim of this study is to evaluate operating conditions during general anesthesia with or without neuromuscular blocker (NMB) in patients undergoing percutaneous internal ring suturing (PIRS). Materials and Methods In this study, 40 patients, with American Society of Anesthesiologists I and II between the ages of 1 and 12 years, were randomly assigned to two groups to receive muscle relaxant with endotracheal tube (ETT) (ETT group) or without muscle relaxant with supreme laryngeal mask airway (sLMA) (LMA group). Anesthesia was maintained with sevoflurane in oxygen (Fio 2 0.3-0.5), thiopental sodium, fentanyl, and rocuronium in ETT group. In LMA group, same protocol was used without rocuronium. Heart rate, blood pressure, peak airway pressure, end-tidal carbon dioxide (EtCO2), and Spo 2 were recorded before and during pneumoperitoneum maintained at a pressure of 8 to 10 mm Hg. Duration of surgery, recovery time, anesthetic time, and grade of quality view were also recorded. Airway problems (cough, hoarseness, laryngospasm, and aspiration) were recorded. Results In LMA group, there was a statistically significant reduction in recovery time versus ETT group (11.6 +/- 4.08 vs. 17.15 +/- 5.32 minutes; p = 0,001). There were no statistically significant differences grade of quality view between the two groups (p = 0.548). There were no statistically significant differences in oxygen saturation (Spo 2), peak airway pressure, and EtCO2 between the two groups before or during insufflation (p > 0.05). Postoperative airway complications were significantly more prevalent in the ETT group. There was no case of inadequate ventilation, regurgitation, or aspiration recorded. Conclusion sLMA is safe and suitable alternative to ETT and NMB is not necessary in general anesthesia with sLMA, pediatric patients undergoing laparoscopic hernia repair with PIRS. PMID- 27548911 TI - Focused Update on Duration of Dual Antiplatelet Therapy for Patients With Coronary Artery Disease. PMID- 27548912 TI - An unembalmed cadaveric preparation for simulating pleural effusion: A pilot study of chest percussion involving medical students. AB - Cadaveric simulations are an effective way to add clinical context to an anatomy course. In this study, unembalmed (fresh) cadavers were uniquely prepared to simulate pleural effusion to teach chest percussion and review thoracic anatomy. Thirty first-year medical students were assigned to either an intervention (Group A) or control group (Group B). Group A received hands-on training with the cadaveric simulations. They were instructed on how to palpate bony landmarks for identifying the diaphragm and lobes of the lungs, as well as on how to properly perform chest percussion to detect abnormal fluid in the pleural space. Students in Group B practiced on each other. Students in Group A benefited from the training in several ways. They had more confidence in their percussive technique (A = mean 4.3/5.0, B = 2.9/5.0), ability to count the ribs on an intact body (A = mean 4.0/5.0, B = 3.0/5.0), and ability to identify the lobes of the lungs on an intact body (A = mean 3.8/5.0, B = 2.3/5.0). They also demonstrated a greater ability to locate the diaphragm on an intact body (A = 100%, B = 60%) and detect abnormal pleural fluid (A = 93%, B = 53%) with greater confidence (A = mean 3.7/5.0, B = 2.5/5.0). Finally, the hands-on training with the unembalmed cadavers created more excitement around learning in Group A compared with Group B. This study shows that simulating pleural effusion in an unembalmed cadaver is a useful way to enhance anatomy education. Anat Sci Educ 10: 160-169. (c) 2016 American Association of Anatomists. PMID- 27548913 TI - Sex hormones establish a reserve pool of adult muscle stem cells. AB - Quiescent satellite cells, known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle following injury throughout life. Although they mainly originate from multipotent stem/progenitor cells of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb 1 (Mib1) expression in myofibres at puberty, which activates Notch signalling in cycling juvenile satellite cells and causes them to be converted into adult quiescent satellite cells. Myofibres lacking Mib1 fail to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Our findings reveal that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofibre niche. Moreover, the same axis regulates the re-establishment of quiescent satellite cell populations following injury. Our data show that sex hormones establish adult quiescent satellite cell populations by regulating the myofibre niche at puberty and re-establish them during regeneration. PMID- 27548914 TI - A single dividing cell population with imbalanced fate drives oesophageal tumour growth. AB - Understanding the cellular mechanisms of tumour growth is key for designing rational anticancer treatment. Here we used genetic lineage tracing to quantify cell behaviour during neoplastic transformation in a model of oesophageal carcinogenesis. We found that cell behaviour was convergent across premalignant tumours, which contained a single proliferating cell population. The rate of cell division was not significantly different in the lesions and the surrounding epithelium. However, dividing tumour cells had a uniform, small bias in cell fate so that, on average, slightly more dividing than non-dividing daughter cells were generated at each round of cell division. In invasive cancers induced by Kras(G12D) expression, dividing cell fate became more strongly biased towards producing dividing over non-dividing cells in a subset of clones. These observations argue that agents that restore the balance of cell fate may prove effective in checking tumour growth, whereas those targeting cycling cells may show little selectivity. PMID- 27548917 TI - Simple and Reliable Fabrication of Bioinspired Mushroom-Shaped Micropillars with Precisely Controlled Tip Geometries. AB - We present a simple yet scalable method with detailed process protocols for fabricating dry adhesives with mushroom-shaped micropillars of controlled tip geometries. The method involves using photo-lithography with a bilayer stack combining SU-8 and lift-off resist, and subsequent replica molding process. This approach utilizes widely used and commercially available materials and can thus be used to generate mushroom-shaped micropillars with precisely controlled tip diameters and thicknesses in a simple, reproducible, and cost-effective manner. The fabricated mushroom-shaped micropillar arrays exhibited highly different tendencies in adhesion strength and repeatability depending on tip geometries, such as tip diameter and thickness, thereby demonstrating the importance of precise tunability of tip geometry of micropillars. The fabricated dry adhesives with optimized tip geometries not only exhibited strong pull-off strength of up to ~34.8 N cm(-2) on the Si surface but also showed high durability. By contrast, dry adhesives with nonoptimized tips displayed low pull-off strength of ~3.6 N cm(-2) and poor durability. PMID- 27548915 TI - Melanoma miRNA trafficking controls tumour primary niche formation. AB - Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialized in releasing pigment vesicles, termed melanosomes. In melanoma in situ, we found melanosome markers in distal fibroblasts before melanoma invasion. The melanosomes carry microRNAs into primary fibroblasts triggering changes, including increased proliferation, migration and pro-inflammatory gene expression, all known features of cancer associated fibroblasts (CAFs). Specifically, melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signalling activation, which reciprocally encourages melanoma growth. Melanosome release inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest an opportunity to block melanoma invasion by preventing the formation of the dermal tumour niche. PMID- 27548918 TI - The current state of diagnostics for meningitis and encephalitis. PMID- 27548916 TI - Kank2 activates talin, reduces force transduction across integrins and induces central adhesion formation. AB - Integrin-based adhesions play critical roles in cell migration. Talin activates integrins and flexibly connects integrins to the actomyosin cytoskeleton, thereby serving as a 'molecular clutch' that transmits forces to the extracellular matrix to drive cell migration. Here we identify the evolutionarily conserved Kank protein family as novel components of focal adhesions (FAs). Kank proteins accumulate at the lateral border of FAs, which we term the FA belt, and in central sliding adhesions, where they directly bind the talin rod domain through the Kank amino-terminal (KN) motif and induce talin and integrin activation. In addition, Kank proteins diminish the talin-actomyosin linkage, which curbs force transmission across integrins, leading to reduced integrin-ligand bond strength, slippage between integrin and ligand, central adhesion formation and sliding, and reduced cell migration speed. Our data identify Kank proteins as talin activators that decrease the grip between the integrin-talin complex and actomyosin to regulate cell migration velocity. PMID- 27548920 TI - Clinical applications of NGS in nucleic acid testing. PMID- 27548919 TI - An overview of HIV and HCV viral load monitoring. PMID- 27548921 TI - The role of laboratory diagnostics in patient management for Graves' disease. PMID- 27548922 TI - Automated analyzers add efficiency to laboratory testing. PMID- 27548923 TI - Diagnostics, over-testing, and patient-centered care. PMID- 27548924 TI - CLIA and regulatory readiness: How can your lab always be ready?. PMID- 27548925 TI - Getting ready for your laboratory inspection. PMID- 27548926 TI - Time for a urinalysis renaissance? The oldest lab test is receiving new attention and applications. PMID- 27548927 TI - Urine studies yield valuable diagnostic insights. PMID- 27548928 TI - What's your lab's strategy? AB - Important strategic choices cascade throughout a laboratory. Senior management should create a document that answers each of the five key questions explained on page 60. Once this has been detailed in writing, it remains important to disseminate the basics to all employees so they are singing the same tune. A useful way to accomplish this is through a coherent strategy statement that specifies three components: 1) objectives; 2) scope; and 3) advantages. Commercial and hospital outreach labs should be in business to win. It all starts with a definition of what winning looks like. To "participate" in your market contributes to mediocrity-and it's self-defeating. With no clear strategic direction of where-to-play and how-to-win choices that associate with the aspiration, a mission or vision statement can be frustrating rather than inspiring for employees. Articulate it plainly and concisely for everybody. With a care-fully prepared and designed strategy, you will be on your way to winning in the zero-sum game! PMID- 27548929 TI - Lipemia and hyperleukocytosis can lead to CBC errors. PMID- 27548930 TI - Recent FDA action against Zika test further validates concerns over proposed LDP regulations. PMID- 27548931 TI - Next generation sequencing paired with data analysis provides accurate pathogen identification. PMID- 27548932 TI - APPROVED: New Antimicrobial Stewardship Standard. PMID- 27548933 TI - Safety Focus: Capturing Medical Device UDIs in the Electronic Medical Record. PMID- 27548934 TI - Standards Changes for Providers of Diagnostic Imaging Services. PMID- 27548935 TI - Consistent Interpretation. PMID- 27548936 TI - [Chemical Characteristics of Particulate Matters and Trajectory Influence on Air Quality in Shanghai During the Heavy Haze Episode in December, 2013]. AB - Intensive haze shrouded central and eastern parts of China in Dec. 2013. In this study, the mass concentrations of gaseous and particulate pollutants, and also the chemical compositions of fine particulate matters were obtained based on in situ measurement in Shanghai urban area. The characteristics of PM2.5 were investigated during different pollution episodes, including dust, haze, fog-haze and long-rang transport episodes. The results showed that pollution was most serious during the fog-haze episode, during which the maximum daily mass concentrations of PM10 and PM2.5 reached 536 microg x m(-3) and 411 microg x m( 3), respectively. During the fog-haze episode, the ratio of PM2.5 to PM10 was over 76.7%, suggesting that high humidity enhanced the secondary formation of NO3 , SO4(2-) and NH4+ in PM2.5. Highest concentration of Ca2+ in PM2.5 occurred during the dust episode and the proportion of primary components in PM2.5 increased obviously. Highest concentration of SO2- was observed in PM25 during the long-range transport episode, with a fast growth rate. Meanwhile, the trajectories reaching Shanghai urban area and cluster analysis during different pollution episodes were simulated by HYSPLIT model. Combined with observation data of PM2.5 in Shanghai urban area, chemical characteristics of PM2.5 in different clusters and potential source apportionment of various pollution episodes were also studied in this study. The result revealed that the air trajectories could be grouped into six clusters based on their spatial similarities. Among these clusters, cluster6 which moved fast was associated with clean air. Cluster2 and cluster3 originating from Mongolia region had strong correlations to dust pollution, along with low PM2.5/PM10 ratio and high concentration of Ca2+ in PM2.5. Compared with other clusters, cluster5 and cluster4 with slow moving speed were more favorable for reactions between particulate species and formation of secondary pollutants during transport. Additionally, the stagnant weather condition under these two clusters with high water vapor when passing over the East China Sea further led to the aggravation of atmospheric pollution in Shanghai. PMID- 27548937 TI - [Analysis of Single Particle Aging and Mixing State at an Agriculture Site (Quzhou) in the North China Plain in Summer Using a Single Particle Aerosol Mass Spectrometer]. AB - To characterize the size distribution and chemical ompsitins f abiet prtices t a agicuturesit intheNorh o Chinese Plain, a single particle aerosol mass spectrometer (SPAMS) was deployed from June 30 to July 8, 2013. A total of 230,152 particles in the size range of 0.2-2.0 pm were chemically analyzed with both positive and negative ion spectra. The results revealed that aerosol could he classified into eight dominant groups, including elemental carbon (EC, 55.5%), organic carbon (OC, 10.7%), alkalis (Na-K, 17.4%), other metals (1.7%), Fe-rich (6.3%), Pb-rich (3.1%), dust (4.8%), and other (0.8%). The observed eight types of particles contained secondary components such as 46NO2-, 62NO3-, 96SO3-, 96SO4 , 97HSO4-, showing that they probably went through different aging processes. The analysis of particle size distribution showed that 700-800 nm was the peak value of all particles, and that dust and Fe particles were mainly in the coarse size range. EC particles subtype group research revealed EC particles tended to be aging with the above mentioned secondary ions and eventually led to a particle type conversion from EC to the less aging ECN and the more serious aging ECS, the diurnal variation of which was obviously negatively correlated, and there was a possibility of forming OC/EC mixture with the adsorption of secondary organic matter on EC surface. PMID- 27548938 TI - [Investigation of Aerosol Mixed State and CCN Activity in Nanjing]. AB - During 11-18 September 2014, the size-resolved aerosol Cloud Condensation Nuclei (CCN) activity and mixing state were measured using Cloud Condensation Nuclei Counter (CCNC), Aerosol Particle Mass (APM) and Scanning Mobility Particle Sizer (SMPS). The results showed that aerosols mainly existed as an internal mixture. For 76, 111, 138 and 181 nm particles, black carbon (BC) accounted for 5.4%, 10%, l0.7% and 6.7% of the particle mass, but as high as 51%, 57%, 70% and 59% of the particle number concentrations, respectively, suggesting that BC was a type of important condensation nuclei in the atmosphere and made significant contributions to particle numbers. The occasionally observed external mixtures were mainly present in 111 and 138 nm particles. The critical supersaturation was 0.25%, 0.13%, 0.06% and 0.015% for 76, 111, 138 and 181 nm particles, respectively. Precipitation and haze had significant effects on the particle CCN activity. The hygroscopicity parameter K was 0.37, 0.29 and 0.39 in rainy, clear and hazy days, respectively. Particle density and CCN activity were impacted by chemical compositions. Compared with clear days, higher contents of inorganic salts and lower contents of organics were found on hazy days, accompanied by lower particle density and higher CCN activity. PMID- 27548939 TI - [Characteristics of Number Concentration Size Distributions of Aerosols Under Processes in Beijing]. AB - The aerosol number concentration size distributions were measured by a Wide-Range Particle Spectrometer (WPS-1000XP) at an urban site of Beijing from 2012 to 2014; and the characteristics of the size distributions in different seasons and weather conditions were discussed. The results showed that the daily average number concentration of Aitken mode aerosols was highest in the spring and lowest in the autumn; the daily average number concentration of accumulation mode aerosols was bigher in the spring and winter, while lowest in summer; and the average concentration of coarse mode was highest during the winter. The Aitken mode particles had the most significant diurnal variations resulted from the traffic sources and the summer photochemical reactions. In the spring, autumn and winter, the number concentrations of accumulation mode of the nighttime was higher than that of the daytime. The coarse mode particles did not have obvious diurnal variation. During the heavy pollution process, the accumulation mode aerosols played a decisive role in PM2.5 concentrations and was usually removed by the north wind. The precipitation could effectively eliminate the coarse mode particles, but it bad no obvious effect on the accumulation mode particles under small speed wind and zero speed wind. During the dust process, the concentrations of coarse mode particles increased significantly, while the accumulation mode aerosol concentration was obviously decreased. PMID- 27548940 TI - [Temporal and Spatial Distribution Characteristics of PM2.5 in Chongqing Urban Areas]. AB - To explore the diurnal and seasonal characteristics of PM25, hourly PM25 concentration data ol It tixed monitoring sites in Chongqing urban area were collected continuously from June 2014 to May 2015. The result showed that: (1) the seasonal concentration of PM2.5 in different seasons decreased in the order of winter, autumn, spring and summer (P < 0.05), which were 100.2 microg x m(-3), 66.1 microg x m(-3), 45.9 microg x m(-3) and 33.4 microg x m(-3), respectively. (2) Monthly average concentrations of PM2.5 showed a single-peak curve, and the peaks of which occurred in January (P < 0.05, 120.8 microg x m(-3)). (3) For the whole year, daily variation of PM2.5 showed a jaggies curve. (4) Diurnal average concentrations of PM2.5 showed an obviously bimodal curve in winter, autumn and spring, hut it was less obvious in summer. (5) Daily PM25 concentration was significantly positively correlated with SO2, NO2 and CO (P < 0.01), indicating that the concentrations of SO2, NO2 and CO had a significant impact on the concentration of PMID- 27548941 TI - [Comparison of Monitoring Methods of Organic Carbon and Element Carbon in Atmospheric Fine Particles]. AB - Accurate measurement of organic carbon (OC) and elemental carbon (EC) in atmospheric fine particulate is an important scientific basis for studying the formation and source apportionment of carbonaceous aerosol. The selection of different analysis programs will lead to difference in the OC and EC concentrations, and further result in the misjudgment of the results. The OC and EC concentrations observed using three temperature protocols including RT-Quartz ( R) , NIOSH 5040 (N) and Fast-TC (F) were compared and analyzed in combination with the degree of air pollution in Beijing. The results showed that there was no significant difference in the TC (TC = OC + EC), OC and EC concentrations observed using R, N and F protocols and certain deviation was found among the TC (TC = OC + EC) , OC and EC concentrations. For TC, the results observed using R protocol were 5% lower than those using N protocol; hut 1% higher than those using F protocol. For OC, the results obtained using R were 9% lower than those using N protocol and 1% higher than those using F protocol. For EC, the results obtained using R were 20% higher than those using N protocol and 11% lower than those using F protocol. The variation coefficients for TC, OC and EC obtained based on R protocol were less than the other two temperature protocols under different air quality degrees. The slopes of regression curves of TC, OC and EC between on-line analysis using R protocol and off-line analysis were 1.21,1. 14 and 1.35, respectively. The correlation coefficients of TC, OC and EC were 0.99, 0.99 and 0.98, respectively. In contrast with the Black carbon ( BC) concentrations monitored by multi-angle absorption spectrophotometer (MAAP), the EC concentrations measured by on-line OC/EC analyzer using R protocol were obviously lower. When the BC concentrations were less than or equal to 8 gg*m3, the EC/BC ratio was 0.39. While the EC/BC ratio was 0.88, when the BC concentrations were greater than 8 ggm3. The variation trends of EC and BC concentrations were similar, while systematic error existed between the results obtained using those two instruments. PMID- 27548942 TI - [Residue Characteristics of Perfluorinated Compounds in the Atmosphere of Shenzhen]. AB - In order to explore the residual characteristics of perfluorinated compounds (PFCs) in the atmosphere of Shenzhen, passive air samplers consisting of polyurethane foam (PUF) disks impregnated with XAD-4 power were deployed at 12 sites in Shenzhen from November 2014 to February 2015. Seven volatile and fifteen ionic PFCs were analyzed. The results indicated that SigmaPFCs concentration ranged from 23.7 pg x m(-3) to 157 pg x m(-3) (mean: 79.0 pg x m(-3)), dominated by volatile PFCs, with 8:2 FTOITI, 6:2 FTOH, PFPeA, PFOA being the dominant compounds. The spatial distribution of volatile and ionic PFCs concentrations was the same, displaying the characteristic of "the northwest being higher than the southeast ". Furthermore, the concentrations of 6:2 FTOHs, 8:2 FTOHs, PFPeA, PFHxA and PFOA had positive correlations with PM2.5 and PM10 (P < 0.05, P < 0.01) and were more positively correlated with the levels of PM10 than those of PM2.5. PMID- 27548943 TI - [Monitoring Atmospheric CO2 and delta(13)C (CO2) Background Levels at Shangdianzi Station in Beijing, China]. AB - The study presented time series of atmospheric CO2 concentrations from flask sampling at SDZ regional station in Beijing during 2007 and 2013, together with delta(13)CO2) values during 2009 and 2013. The "representative data" of CO2 and delta(13)C (CO2) were selected from the complete data for further analysis. Annual CO2 concentrations increased from 385.6 x 10(-6) in 2007 to 398.1 x 10(-6) in 2013, with an average growth rate of 2.0 x 10(-6) a(-1), while the delta(13)C values decreased from -8.38% per hundred in 2009 to -8.52% per hundred in 2013, with a mean growth rate of -0.03% per hundred x a(-1). The absolute increase of CO2 from 2007 to 2008 reached the lowest level during 2007 and 2013, possibly due to relatively less carbon emissions during the 2008 Olympic Games period. The peak-to-peak amplitudes of atmospheric CO2 and delta(13)C seasonal variations were 23. 9 x 10 -6 and 1. 03%o, respectively. The isotopic signatures of CO2 sources/sinks were also discussed in this study. The delta8 value for heating season I (Jan. 01-Mar. 14) was -21.30% per hundred, while -25.39% per hundred for heating season 11 (Nov. 15-Dec.31) , and for vegetative season (Mar. 15-Nov. 14) the delta(bio) value was estimated to be -21.28% per hundred, likely suggesting the significant impact of fossil fuel and corn straw combustions during winter heating season and biological activities during vegetative season. PMID- 27548944 TI - [Concentration and Size Distribution of Bioaerosols in Indoor Environment of University Dormitory During the Plum Rain Period]. AB - Bioaerosols of university dormitory can spread through air and cause a potential health risk for student staying in indoor environment. To quantify the characteristics of bioaerosols in indoor environment of university dormitory, concentration and size distribution of culturable bioaerosols were detected during the plum rain period, the correlations of culturable bioaerosol with concentration of particulate matter, the ambient temperature and relative humidity were analyzed using Spearman's correlation coefficient and finally the changes of size distribution of culturable bioaerosol caused by activities of students were detected. The results showed that the mean concentrations of culturable airborne bacteria and fungi were (2133 +/- 1617) CFUm' and (3111 +/- 2202) CFU x m(-3). The concentrations of culturable airborne bacteria and fungi exhibited negative correlation with PM1, PM2.5, and PM10, respectively. The respirable fractions of bacteria exhibited positive correlation with PM2.5, and the respirable fractions of fungi exhibited significant positive correlation with PM10. Ambient temperature had positive correlation with culturable airborne bacteria and fungi, and relative humidity had negative correlation with culturable airborne bacteria and fungi. In the afternoon, concentrations of culturable airborne fungi in indoor environment of university dormitory significantly increased, and the size distribution of culturable hioaerosols was different in the morning and afternoon. PMID- 27548945 TI - [Air Microbial Pollution and Health Risk of Urban Black Odorous Water]. AB - Aiming at the possihle air microbial pollution of urban black odorous water the contamination characteristics of bacteria, fungi and total microbe as well as health risks of different types of population within certain distance from the urban black odorous water were studied. The results showed that hbcteria and fungi pollution was primary within offshore 200 m; under near calm condition, there was an aggregation phenomenon of microorganisms within offshore 20 m; the concentrations of bacteria, fungi and total microbe were the highest in the morning, the middle at noon, and the lowest in the afternoon; within offshore 200 m, the width of black odorous water was significantly correlated with the concentrations of bacteria, fungi and total microorganisms; the microbial health risk of residents mainly existed in the offshore 100 m range; at the same offshore distance, the short-term exposure health risk to children was the greatest, followed by women, men to a minimum. PMID- 27548946 TI - [Particle Size Distribution, Seasonal Variation Characteristics and Human Exposure Assessment of Heavy Metals in Typical Settled Dust from Beijing]. AB - Four types of dust from dormitories, offices, hotels and roads in Beijing were collected and fractionated into 9 fractions, respectively. Totally 36 samples were obtained and analyzed for heavy metals including Cu, Zn, Cr, Pb, Cd and Ni. Particle size distributions of those heavy metals in these four types of dust were investigated and the influencing mechanisms were discussed. Distribution patterns of the same heavy metal in different types of dust showed various characteristics. Also different metals in the same type of dust represented different distribution patterns. Heavy metals in road dust tended to concentrate in finer particles. Two offices from the same building, located in Beijing, China, were selected to study the seasonality of heavy metals in dust. Dust sampling from Office A was conducted at weekly intervals between March 2012 and August 2012, while dust from Office B was sampled fortnightly from March 2012 to December 2012. Generally, levels of all heavy metals remained stable among different seasons, however, Cr and Pb represented more significant fluctuations than other four heavy metals. Based on the geo-accumulation index method, the pollution of Zn, Cu and Pb was more serious in the investigated samples, and dust from offices and hotels were moderately polluted by Zn. According to the risk assessment results, the carcinogenic health risks of the six heavy metals in the four types of dust were negligible. PMID- 27548947 TI - [Distribution Characteristics and Source Analysis of Polycyclic Aromatic Hydrocarbons (PAHs) in Surface Dust of Xi'an City, China]. AB - A total of 58 surface dust samples were collected from Xi'an city. The concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) were analyzed by gas chromatography with a flame ionization detector (GC-FID). At the same time, the distribution and sources of PAHs in surface dust were studied. The results showed that the concentrations of individual PAH ranged from 14.69 to 6370. 48 microg x kg(-1), and the total concentrations of 16 PAHs (?16 PAHs) ranged from 5039.67 to 47,738.50 microg x kg(-1), with a mean of 13,845.82 microg x kg(-1). Compared to the Y PAHs levels of other cities, the ?16 PAHs in surface dust of Xi'an belonged to a relatively higher level. PAHs in surface dust were mainly dominated by high molecular weight PAHs with 4-6 rings and the concentration of 7 carcinogenic PAHs (1 CPAHs) accounted for 46.08% of 3 16PAHs. The mean of ?16 PAHs in surface dust had the highest concentration at industrial area; followed by the educational area, traffic area, business and traffic area; residential area and parks showed relatively lower concentration. The average content of ?16 PAHs in surface dust presented an increasing trend along the main urban area--the second ring road--the third ring road. ?16 PAHs in surface dust had higher concentrations at the industrial areas of the east and west suburbs of Xi'an, the south suburb and the north section of the second ring road; ?16 PAHs concentrations in the main urban area, north suburb and southeast part of Xi'an were relatively lower. The results of ratio, cluster analysis and principal component analysis showed that PAHs in surface dust were mainly originated from the combustion of fossil fuels and coal combustion. Among them, diesel combustion reached 36.07%, gasoline combustion accounted for 32.31%, and coal combustion was resposbe for 23.40% PMID- 27548948 TI - [Toluene, Benzene and Acetone Adsorption by Activated Carbon Coated with PDMS]. AB - To improve the adsorption selectivity of volatile organic compounds ( VOCs) , activated carbon ( AC) was modified by polydimethylsiloxane (PDMS) and characterized by BET analysis and Boehm titration. Dynamic adsorption column experiments were conducted and Yoon-Neslon(Y-N) model was used to identify adsorption effect for toluene, beuzene and acetone on AC when relative humidity was 0%, 50% and 90%, respectively. The results showed that the BET area, micropore volume and surface functional groups decreased with the PDMS modification, and surface hydrophobicity of the modified AC was enhanced leading to a lower water adsorption capacity. The results of dynamic adsorption showed that the adsorption kinetics and capacity of Bare-AC decreased with the increase of relative humidity, and the adsorption capacities of PDMS coated AC were 1.86 times (toluene) and 1.92 times (benzene) higher than those of Bare-AC, while a significant improvement of adsorption capacity for acetone was not observed. These findings suggest that polarity of molecule can be an important influencing factor for adsorption on hydrophobic surface developed by PDMS. PMID- 27548949 TI - [Distribution Characteristics, Sources and Pollution Assessment of Trace Elements in Surficial Sediments of the Coastal Wetlands, Northeastern Hainan Island]. AB - Totally 128 surficial sediments samples were collected from the coastal wetlands, northeastern Hainan Island and analyzed for their concentrations of 14 elements including Al2O3, Fe2O3, MnO, Cu, Ni, Sr, Zn, V, Pb, Cr, Zr, As, Cd and Hg, TOC and grain sizes. The mean concentrations of trace metals V, Cr, Ni, Cu, Zn, As, Pb, Cd and Hg were (40.13 +/- 32.65), (35.92 +/- 26.90), (13.03 +/- 11.46), (11.56 +/- 10.27)-, (48.75 +/- 27.00), (5.48 +/- 1.60), ( 18.70 +/- 8.66), (0.054 +/- 0.045 ), (0.050 +/- 0.050) microg x g(-1), respectively, which were much lower than those in Pearl River Estuary, Yangzi River Estuary, Bohai Bay, upper crust and average shale. The average concentrations of Sr and Zr were much higher, reaching up to (1253.60 +/- 1649.58) microg x g(-1) and (372.40 +/- 516.49) microg x g(-1), respectively. The spatial distribution patterns of Al2O3, Fe2O3, MnO, Cu, Ni, Zn, V, Pb, Cr, Cd and Hg concentrations were the same as each other except for those of As, Sr and Zr. Generally, relatively high concentrations of these elements only appeared in the Haikou Bay, Nandu estuary, Dongzhai Harbor, Qinglan Harbor and Xiaohai in study area. The factor analysis revealed that the trace elements Al2O3 Fe2O3, MnO, Cu, Ni, Zn, V, Pb, Cr and part of Hg were mainly originated from the rock material by natural weathering processes, while the Cd and a part of Hg were from the biological source controlled by TOC. As and part of MnO were influenced by anthropogenic source, especially by aquacultures. Zr and some MnO were derived from heavy minerals dominated by the coarse grain of sediments. In contrast to the ERL, ERM and the results of enrichment factors (EF) , the environment of study area was good in general and the degree of contamination by trace elements was low on the whole. However, there are still some places where anthropogenic input have caused serious enrichments of trace elements and the occasional adverse effect on benthic organism induced by Ni could probably occur in 22% areas of all the sampling stations. PMID- 27548950 TI - [Heavy Metals Accmultio in the Caofeidian Reclamation Soils: Indicated by Soil Magnetic Susceptibility]. AB - The environmental magnetism method has been widely applied to identify soil heavy metal pollution, which is characterized by simplicity, efficiency, non destructivity and sensitivity. The present study used magnetic susceptibility to assess the accumulation of heavy metals in soils of the Caofeidian industrial zone which is a typical reclamation area in northern China. The study area was divided into three sub-zones based on the function, including industrial zone, living zone, natural tidal flat and wetland. A total of 35 topsoil samples (0-10 cm) and 3 soil profiles were collected from the three sub-zones. Magnetic susceptibility (X(lf)), iron oxide (Fe2O3) contents and heavy metals contents (Cr, Ni, Cu, Zn, As, Pb, Mn and V) of the samples were analyzed. The results showed that X(lf) values and heavy metals contents exhibited higher spatial variability in the top soil of the industrial zone, indicating the severe impacts of industrial activities. In the soil profiles of the industrial and living zones, all heavy metals were enriched to different degrees in the upper layer (0 20 cm). However, there was no significant change of heavy metal contents in the soil profiles of tidal flat which was far from the industrial area. The X(lf) value was significantly (P < 0.01) positively correlated with the contents of Fe2O3, Ni, Cu, As and V in the industrial top soil. This indicated that X(lf) could be used as an indicator for heavy metal accumulation in the industrial zone. However, the X(lf) value was not suitable to be an indicator to show the heavy metal accumulation in the soils of living zone and natural tidal flat. This might be associated with the different sources of magnetic materials among the different sub-zones and the special characteristics of the soils in the tidal flat and wetland. PMID- 27548951 TI - [Characteristics of Stable Isotopes in Precipitation and Their Moisture Sources in Mengzi Region, Southern Yunnan]. AB - The deltaD and delta18O values in precpitation have disciplinary variations, and they have close connections with meteorological parameters and moisture sources. Based on the continuously collected precipitation samples in Mengzi from Jan. 2009 to Dec. 2011, the reanalysis data from the European Centre for Medium-Range Weather Forecasts (ECMWF) and the National Centre for Environmental Prediction/National Centre for Atmospheric Research (NCEP/NCAR), and the Hybrid Single-Particle Lagrangian Integrated Trajectory for 4.8 (HYSPLIT_4.8) model, we analyzed the variations of deltaD and delta18O in precipitation at synoptic scale in Mengzi, and the relations between delta18O in precipitation and air temperature, delta18O in precipitation and amount, delta18O in precipitation and wind speed, delta18O in precipitation and moisture sources. The results showed that the variations of deltaD and delta18O values in precipitation exhibited remarkable seasonal variability. The stable isotopic values in precipitation were higher during dry season than those during wet season. The relations between delta18O in precipitation and air temperature, delta18O in precipitation and amount indicated significant negative correlations. However, it exhibited significant positive correlation between precipitation delta18O and wind speed at different pressure levels (300 hPa, 500 hPa, 700 hPa, and 800 hPa), and this result indicated that the wind speed was an important influencing factor for the variations of precipitation delta18O. With the increasing rainfall levels, the intercept and slope of meteoric water line also increased, and this phenomenon suggested that there was a secondary evaporation effect under sub-cloud in stable isotopes of precipitation. The backward trajectory model showed that the main moisture sources during dry season came from the westerly and the inland. However, during wet season, the remote ocean vapor was the main moisture source in Mengzi, and the delta18O values in precipitation were much lower during typhoon period. PMID- 27548952 TI - [GIS Spatial Distribution and Ecological Risk Assessment of Heavy Metals in Surface Sediments of Shallow Lakes in Jiangsu Province]. AB - To understand pollution of heavy metals in surface sediments of shallow lakes, surface sediments samples of 11 lakes in Jiangsu province were collected to determine the content of six heavy metals including As, Cr, Cu, Pb, Zn and Ni. GIS was used to analyze the spatial distribution of heavy metals, and geological accumulation index (Igeo), modified contamination index (mCd) pollution load index (PLI) and potential ecological risk index (RI) were used to evaluate heavy metal contamination in the sediments. The results showed that: in the lakes' surface sediments, the average content of As, Cu, Zn, Cr, Pb, Ni in multiples of soil background of Jiangsu province were 1.74-3.85, 0.65-2.66, 0.48-3.56, 0.43 1.52, 0.02-1.49 and 0.12-1.42. According to the evaluation results of Igeo and RI, As, which had high degree of enrichment and great potential ecological risk, was the main pollutant, followed by Cu, and pollution of the rest of heavy metals was relatively light. Combining the results of several evaluation methods, in surface sediments of Sanjiu Lake, Gaoyou Lake and Shaobo Lake, these heavy metals had the most serious pollution, the maximum pollution loading and moderate potential ecological risk; in surface sediments of Gehu Lake, Baima Lake and Hongze Lake, some regions were polluted by certain metals, the overall trend of pollution was aggravating, the pollution loading was large, and the potential ecological risk reached moderate; in the other 5 lakes, the risk of sediments polluted by heavy metals, as well as the pollution loading, was small, and the overall was not polluted. PMID- 27548953 TI - [Microcosm Simulation Study and Methylmercury Forming Mechanism at Landscape Water of City]. AB - Mercury is harmful to the environment, which has gradually become one of the research hotspots. Sediments, as a main repository of pollutants, have an important impact on water quality and the internal organisms, which deserves our research. In this paper, we focused on Hefei landscape water sediment and tried to investigate the status of inorganic mercury and methylmercury pollutions in the sediment. To study the conversion process from inorganic mercury to methylmercury and their enrichment levels and mechanism, we established the ecological chain of "sediment-water-grass-fish" through analog microcosm examination. The results were as follows: from ten water and sediment samples in Hefei landscape water sediment, we found that the contents of inorganic mercury and methylmercury ranged 11.74-13.12 ug . kg-1 and 0.37-2.23 ug . kg-1, respectively. The microcosm examination showed that: with increasing culture time, inorganic mercury in sediments gradually decreased. There was a phenomenon that the content of methylmercury increased at first and then decreased to reach the balance later. Both the inorganic mercury and methylmercury in water change showed an increasing trend. The enrichment contents of inorganic mercury in Egeria densa Planch, and golden mandarin fish (Siniperca scherzeri Steindachner) were low while their enrichment of methylmercury could he great. In addition, we found that both the bioaccumulation ability and the enrichment coefficient of methylmercury in the body of golden mandarin fish were the maximum during the same period. PMID- 27548954 TI - [Seasonal Stratification and the Response of Water Quality of a Temperate Reservoir--Zhoucun Reservoir in North of China]. AB - In order to reveal the seasonal stratification and the response of water quality of a temperate reservoir Zhoucun Reservoir in North of China. The physical, chemical and phytoplankton indexes were continuously monitored from July 2014 to June 2015. The results showed that the thermal stratification was monomictic, which lasted from April to October. The thermal stratification played an important role in the change of water environment. The hypoxia in the bottom water caused hy thermal stratification led to the release of nutrients and reductants from sediment. During the stratification period, the mean concentrations of total nitrogen, total phosphorus, manganese and sulfide were 1.18, 0.11, 0.47 and 0.48 mg . L-1, respectively. The vertical distribution of phytoplankton was significantly influenced by water temperature stratification. During the thermal stratification period, phytoplankton abundance was higher and the average phytoplankton ahundance was 16.35 x 106 cells . L-1 in the upper water of the reservoir, while remained at low levels at the bottom. PMID- 27548955 TI - [Hydrochemical Characteristics of Snow Meltwater and River Water During Snow melting Period in the Headwaters of the Ertis River, Xinjiang]. AB - To analyze the hydrochemical characteristics of river water and snow meltwater during snow-melting period in the Kayiertesi River, the headwaters of the Ertis River, samples of river water and meltwater were collected every day during March and April, 2014. Furthermore, the combination of descriptive statistics, Gibbs Figure and Piper Triangular diagrams of anions and cations were used for hydrochemical analyses. The results showed that the major ion compositions and hydrochemical types were significantly different between river water and snow meltwater. The total dissolved solid (TDS) in the river water ranged from 24.9 to 50.3 mg . L-1. The major cations of river water were Ca2+ and Na+, accounting for 61% and 17% of the total cation equivalent concentration, respectively. Meanwhile, HCO3- constituted about 95% of the total anions concentration. The hydrochemical type of river water was HCO3--Ca2+. The chemical composition of river water samples located in the middle with a deviation to left of Gibbs model, indicating that the major chemical process of river water was controlled by rock weath ring and precipitation but rock weathering played a more important role. PMID- 27548956 TI - [Relationship Between the Phytoplankton Distribution and Environmental Factors in Fenhe Scenic Spot of Taiyuan]. AB - In order to explore the structural characteristics of phytoplankton community and the water quality and the water quality of the Fenhe scenic spot in Taiyuan, the species composition and the biomass of phytoplankton as well as their correlation with the environmental factors were monitored. The survey selected 9 sampling sites along the up and lower reaches in Fenhe scenic spot of Taiyuan, from Chaicun Bridge to Xiangyun Bridge. During the wet season (June-Octoher) in 2014, specimens were collected, qualitative and quantitative investigation on the algae and monitoring on physicochemical indexes of the water were studied. Meanwhile, the water quality was analyzed and evaluated combining all the physicochemical indexes and cell density. Correlation analysis and RDA were conducted to analyze the relationship of algal community structure and the environmental factors. The main results showed that the dominant phytoplanktons were Cyanophyta, Chlorophyta and Bacillariophyta. The algal biomass first increased and then reduced during the wet season, and the maximum value of hiomass occurred in July. There were many differences among different sampling points. The cell densities of phytoplankton were much higher in three central areas than the other sampling sites. Physical and chemical factors showed a variation tendency in time and space. Based on the results of RDA hetween phytoplankton cell densities and the physic-chemical parameters, the cell densities and the physic..chemical parameters had different correlations. The total cell density had significant positive correlation with dissolved oxygen, and negative correlation with COD. There were extremely significant positive correlations between diatom cell densities and water temperature, air temperature. But the diatom cell density was obviously negatively correlated with COD. It was distinct that the functions of the environment factors were different in temporal and spatial distrihution. The state index of comprehensive nutrition indicated that the total nitrogen content was beyond the standard in all sampling sites during the whole wet season. The water quality varied from oligotrophic to light eutrophic. PMID- 27548957 TI - [Distribution Characteristics of Nitrifiers and Denitrifiers in the River Sediments of Tongling City]. AB - Rivers in mining areas were influenced by contaminants such as nitrogen, phosphorus and organic matter due to domestic and agricultural wastewater discharge in addition to pollutants caused by mining activities. In this study, surface sediment samples of rivers in Tongling city were collected to address the effect of season and pollution type on the abundance of nitrifiers and denitrifiers using quantitative polymerase chain reaction (QPCR) technique targeting at the ammonia monooxygenase (amoA) and nitrite reductase (nir) genes. The results showed that the average ahundance of ammonia oxidizing archaea (AGA) (ranging from 1.74 x 105 to 1.45 x 108 copies . g-1) was 4.39 times that of ammonia oxidizing hacteria (AGH) (ranging from 1.39 x 105 to 3.39 x 107 copies . g-1); and the average abundance of nirK gene (ranging from 4.45 x 106 to 1.51 x 108 copies . g) was almost a thirtieth part of nirS gene (ranging from 1.69 x 107 to 8.55 x 109 copies . g-1). The abundance of AOA was higher in spring and autumn, and lower in summer and winter. And sediment AOB abundance was higher in spring and winter than in summer and autumn. Meanwhile, the abundance of nir genes was in the order of spring (nirS )/autumn (nirK) > summer > winter > autumn (nirS )/spring (nirK). Moreover, the abundance of bacterial and archaeal arnoA and nirS genes in sediments influenced by mine pollution was generally higher than that in sediments influenced by agricultural non-point pollution, whereas the abundance of nirK gene showed an opposite trend. PMID- 27548958 TI - [Contribution of Base Flow to Total Nitrogen Loading in Subtropical Agricultural Catchments]. AB - With the fast development of economics and improvement of people's living standard, non-point source pollution of the agricultural catchments in subtropical China has become more and more severe, where water quality deterioration has become a main barrier for sustainable development and ecological restoration. The process of ecohydrology in catchment is greatly influenced by the process of base flow in channel. This study selected the Tuojia and Jianshan catchments located in Changsha County, Hunan Province, to quantify and compare the contribution of base flow to total nitrogen (TN) loading from January 2011 to December 2013, through field observation and model estimation. The results suggested that the Tuojia catchment with higher intensity of rice agriculture had the greater volume of base flow, higher average flow-weighted TN concentration in base flow, and greater monthly TN loading via base flow [15.2 mm . month-1, 4.14 mg . L-1 and 0.54 kg . (hm2 . month)-1, respectively] than those in the Jianshan catchment with lower intensity [11.4 mm . month-1, 1.72 mg . L-1 and 0.20 kg . (hm2 . month)-1, respectively]. The base flow contribution to TN loading showed an apparently seasonal pattern. During rice-growing seasons, the contributions of base flow to TN loading were 23.2% and 18.6% in the Tuojia and Jianshan catchments, respectively, lower than those in the fallow seasons (46.9% and 40.0% correspondingly. These results suggested that rice agriculture increased the contribution of base flow in the fallow season to TN loading. Therefore, to alleviate the suffering of non-point source pollution in the rice agriculture catchments, reasonable management measure of rice fields should be implemented to decrease contrihution of base flow to TN loading. PMID- 27548959 TI - [Characteristics and Transport Patterns of Ammonia, Nitrites, Nitrates and Inorganic Nitrogen Flux at Epikarst Springs and a Subterranean Stream in Nanshan, Chongqing]. AB - In a karst groundwater system, it develops complex multiple flows because of its special geological structure and unique physical patterns of aquifers. In order to investigate the characteristics and transport patterns of ammonia, nitrite and nitrate in epikarst water and subterranean stream, the water samples were collected monthly in a fast-urbanizing karst region. The results showed distinctive characteristics of three forms of inorganic nitrogen. The concentration of inorganic nitrogen was stable in the epikarst water while it was fluctuant in the subterranean stream. Epikarst water was less affected by rainfall and sewage compared with subterranean stream. In epikarst water, the nitrate concentration was much higher than the ammonia concentration. Dissolved inorganic nitrogen, mainly from non-point source pollution related to agricultural activities, passed in and out of the epikarst water based on a series of physical; chemical and biological processes in the epikarst zone, such as ammonification, adsorption and nitrification. On the contrary, subterranean stream showed a result of NH4+-N > NO3--N in dry seasons and NO3--N > NH4+-N in rainy seasons. This can be due to the fact that sanitary and industrial sewage flowed into subterranean river through sinkholes, fissures and grikes in dry season. Dissolved inorganic nitrogen in subterranean river was mainly from the non-point source pollution in wet season. Non-point source pollutants entered into subterranean water by two transport ways, one by penetration along with vadose flow through fissures and grikes, and the other by conduit flow through sinkholes from the surface runoff, soil water flow and epikarst flow. The export flux of DIN was 56.05 kg . (hm2 . a)-1, and NH4+-N and NO3--N accounted for 46.03% and 52.51%, respectively. The contributions of point-source pollution and non point-source pollution to the export flux of DIN were 25.08% and 74.92%, respectively, based on run-off division method. PMID- 27548960 TI - [Pollution Characteristics and Evaluation of Nitrogen, Phosphorus and Organic Matter in Sediments of Shanmei Reservoir in Fujian, China]. AB - In order to illuminate pollutants distribution characteristics in sediment of Shanmei Reservoir, sediment samples at 47 sampling stations were collected (include 8 column samples), and concentrations of total nitrogen, total phosphorus and organic matter in the sediment of each station were measured. C/N and the correlation of TN, TP and OM were also analyzed. Finally, pollution assessment for contaminated layer sediments was conducted. The results showed that the average contents of TN, TP and OM (mass fraction) were 1,180 mg . kg-1, 642 mg . kg-1 and 3.30% in the contaminated layer of sediments. Concentrations of total nitrogen and total phosphorus were low and stable at the depth of the normal layer. C/N of the contaminated layer of sediments was much higher than those in normal lakes, which showed that large part of OM came from natural land based sources. Besides, a small part of OM came from phytoplankton, zooplankton and algae. Any two of TN,TP and OM were significantly correlated. This result showed that most of the nitrogen and phosphorus were in the organic form, and they came from similar sources. Evaluation results showed that both organic index and organic nitrogen belonged to the clean category. TP was at a moderate pollution level but not far from the category of heavy pollution. PMID- 27548961 TI - [Effect of Elodea nuttallii-immobilized Nitrogen Cycling Bacteria on Nitrogen Removal Mechanism in an Inflow River, Gonghu Bay]. AB - Undisturbed sediment cores and surface water from Qinshui River in Gonghu Bay were collected to carry out a simulation experiment in our laboratory. The remediation effect of Elodea nuttallii-Immobilized Nitrogen Cycling Bacteria (INCB) was applied in the polluted inflow river. The denitrification rate, ANAMMOX rate and nitrogen microorganism diversity were measured by 15N isotope pairing technology and high-throughput sequencing technology based on 16S rRNA. The TN, NH4+-N, NO3--N concentrations were reduced by 72.03%, 46.67% and 76.65% in the treatment with addition of Elodea nuttallii and INCB in our laboratory experiment. Meanwhile, denitrification bacteria and ANAMMOX bacteria had synergistic effect with each other. The denitrification and ANAMMOX rates were increased by 165 umol (m2 . h)-1 and 269.7 umol . (m2 . h)-1, respectively. The diversities of denitrification and ANAMMOX bacteria also increased in our experiment. From the level of major phylum, Proteobacteria, Planctomycetes, Acidobbacteria and Bacteroidetes all increased significantly. The results showed that the Elodea nuttallii-INCB assemblage technology could increase the bio diversity of nitrogen cycling bacteria and promote the ability of nitrogen removal in Qinshui River. PMID- 27548962 TI - [Spatial and Temporal Distribution Characteristics of Different Forms of Phosphorus in Three Sorts of Rivers around Lake Taihu]. AB - Different forms of phosphorus from the upper reaches of river to lower reaches of river in nine rivers were analyzed to clarify the pollution characteristics of industrial effluent, agriculture effluent and sanitary wastewater to Lake Taihu in February (low water period), May (average water period) and August (abundant water period) of 2009. The results showed that total phosphorus (TP) dissolved total phosphorus (DTP) and soluble reactive phosphorus ( SRP) mass concentration all showed decreasing trend while enzymatic phosphorus (EHP) mass concentration increased with the increase of algal biomass from low water period to abundant water period. Mass concentrations of several forms of phosphorus were all the highest in the rivers impacted by sanitary wastewater, but sanitary wastewater's self-purification capabity from the upper reaches of river to lower reaches of river was the best, and the pollution to Lake Taihu was the lowest. Pollution from rivers impacted by industrial effluent was the highest. Mass concentration of EHP was higher than that of SRP in most cases, so EHP played an important role in Cyanbacterial harmful algal blooms events in Lake Taihu. PMID- 27548963 TI - [Distribution of Phosphorus Forms in the Overlying Water Under Disturbance with the Addition of Algae]. AB - Distribution of different phosphorus (P) forms in the overlying water and the contribution of different algae to the P disappearance were investigated under disturbance with the addition of algae (Microcystis aeruginosa and Selenastrum capricornutum, respectively). The sediments and overlying water were taken from Meiliang Bay in Taihu Lake. The results showed that the concentrations of total P (TP), dissolved total P (DTP), dissolved inorganic P (DIP) and biavailable P (BAP) decreased with and without disturbance. The uptake of DTP and DIP by Microcystis aeruginosa was better than that of Selenastrum capricornutum under the disturbance, but it was the opposite without the disturbance. The disappearance of P in the overlying water was attributed completely to the physico-chemical adsorption of the suspended solids and the uptake of algae. But the contribution of suspended solids and algae depended on the disturbance. The contribution of Microcystis aeruginosa and Selenastrum capricornutum to DTP and DIP absorption was about 60% without disturbance. However, the value was reduced to 40% (Microcystis aeruginosa) and 25% ( Selenastrum capricornutum) under the disturbance. Under the disturbance and the action of algae, the distribution of sedimentary P forms changed. NH4 Cl-P and Ca-P release and Fe/Al-P increase were observed with and without disturbance. The decrease of NH4 Cl-P and Ca-P and the increase of Fe/Al-P were more obvious with disturbance than without disturbance. Selenastrum capricornutum was favor of the release of Ca-P and the formation of Fe/Al-P. PMID- 27548964 TI - [Impacts of Sediment Disturbance on the Distribution of Suspended Particle Size and Phosphorus]. AB - To clarify the influence of the sediments disturbance on the particle size distribution of suspended solids, and the influence of particle distribution on the forms of dissolved phosphorous in the overlaying water, the sediments and overlying water from Meiliang Bay, Taihu Lake, were used to conduct the indoor simulation experiments to investigate the particle size of suspended solids according to the Ubbelobde particle size criteria and the distribution of phosphorus compounds in the overlying water under the disturbance circumstances. The results indicated that the average proportions of small (0-10 microm), middle (10-20 microm) and large (> or = 20 microm) diameter particles presented different trends of increasing, decreasing and staying stable, respectively. It indicated the possible transformation of particle size of suspended solids from small-middle diameter to large diameter. In addition, the data of DTP/TP and DIP/TP showed a periodical variation with the corresponding periodical variety of particle diameter in suspended solids, while ns obvious variety of DTP and DIP was observed. It suggested that disturbance enhanced the ability of phosphorus immobilization by suspended solids. On the other band, the percentages of DTP in TP and DIP in TP were 19% and 13% under the disturbance, respectively, and they were obviously lower than those (DTP/TP, 80% and DIP/TP, 69% ) in the control. It indicated that tbs transformation of particle size of suspended solids from small middle diameter to large diameter due to disturbance was in favor of tbe adsorption and sedimentation of dissolved phosphorus. Accordingly, the formation of particle phosphorus was enhanced. Therefore, it delayed the development of eutrophication in the water body. PMID- 27548965 TI - [Effect of Zirconium Modified Kaolin-Based Cap on Migration and Transformation of Phosphorus Between Sediment and Overlying Water]. AB - In this study, microcosm incubation experiments were conducted to investigate the effect of zirconium modified kaolin (ZrMK)-based cap on the migration and transformation of phosphorus (P) between sediments collected from a heavily polluted river and overlying waters under anaerobic conditions. The results showed that a large amount of P was released from the sediments into the overlying water column under anaerobic conditions, and the overwhelming majority of P in the overlying water existed in the form of phosphate. The flux of P from the anaerobic sediments was slightly reduced by the kaolin-based cap, while significantly reduced by the ZrMK-based cap. Sequential extraction of P from the kaolin-based cap at the end of incubation experiments suggested that 29% of P adsorbed by kaolin existed as the bicarbonate-dithionite extracted P (BD-P), and 63% of adsorbed P existed as the residual P (Res-P). Sequential extraction of P from the ZrMK-based cap at the end of incubation experiments suggested that 90% of P adsorbed by ZrMK existed as the NaOH extractable P (NaOH-P) and Res-P, which were unlikely to be released under anaerobic conditions. Compared with no capping, sediments capping with ZrMK did not promote BD-P release from the sediments under anaerobic conditions, but promoted the formation of NaOH-P in the sediments. X-ray photoelectron spectroscopy (XPS) and solid state 31P nuclear magnetic resonance (NMR) analyses of ZrMK-based caps before and after sediment incubation experiments indicated that the adsorption of P by the ZrMK-based caps followed the ligand exchange and inner-sphere complexing mechanism. Results of this work indicate that ZrMK is a promising active capping material for controlling P release from sediments in heavily polluted rivers. PMID- 27548966 TI - [Toxicity of 4-Chlorophenol Solution Under Electrochemical Reduction-oxidation Process]. AB - The Pd-Fe/graphene multi-functional catalytic cathode was prepared by UV-assisted photocatalytic reduction. The catalytic cathode and a Ti/IrO2/RuO2 anode consisting of both three-electrode system (two cathodes) and two-electrode system (one cathode) were designed for the degradation of 4-chlorophenol in aid of olectrochemical reducing and oxidizing processes. The concentrations of the intermediates and products were monitored by high performance liquid chromatography (HPLC), total organic carbon (TOC), and ion chromatography (IC). The theoretical toxicity was calculated according to the formula. The actual toxicity of the solution during the degradation process was detected using the luminescent bacteria. The comparison of the actual toxicity and theoretical toxicity was performed to analyze the trend of the two systems. The results showed that the toxicity of the solution in anode compartment first increased and then decreased, but the toxicity in cathode compartment decreased during the whole degradation for both systems. This trend could be attributed to the intermediate formed, benzoquinone. Through the analysis of correlation, the correlation coefficient was 1 of the theoretical toxicity and actual toxicity at the level of P = 0.01, which indicated the result of toxicity was reliable. The toxicity of three-electrode system was lower than that of two-electrode system after 120 mm. The three-electrode system was considered to be better than the two electrode system. Therefore, the detection of actual toxicity in electrochemical reducing and oxidizing process for the degradation of chlorophenols in the actual industry has wide application prospect. PMID- 27548967 TI - [Removal and Recycle of Phosphor from Water Using Magnetic Core/Shell Structured Fe3O4 @ SiO2Nanoparticles Functionalized with Hydrous Aluminum Oxide]. AB - A novel magnetic core/shell structured nano-particle Fe3O4@ SiO2phosphor-removal ahsorbent functionalized with hydrous aluminum oxides (Fe3O4@ SiO2@ Al2O3. nH2O) was synthesized. Fe3O4@ SiO2@ Al2O3. nH2O was characterized by XRD, TEM, VSM and BET nitrogen adsorption experiment. The XRD and TEM results demonstrated the presence of the core/shell structure, with saturated magnetization and specific surface area of 56.00 emu . g-1 and 47.27 m2 . g-1, respectively. In batch phosphor adsorption experiment, the Langmuir adsorption maximum capacity was 12.90 mg . g-1 and nearly 96% phosphor could be rapidly removed within a contact time of 40 mm. Adsorption of phosphor on Fe3O4@ SiO2@ Al2O3 . nH2O was highly dependent on pH condition, and the favored pH range was 5-9 in which the phosphor removal rate was above 90%. In the treatment of sewage water, the recommended dosage was 1.25 kg . t-1. In 5 cycles of adsorption-regeneration-desorption experiment, over 90% of the adsorbed phosphor could be desorbed with 1 mol . L-1 NaOH, and Fe3O4@ SiO2@ Al2O3. nH2O could be reused after regeneration by pH adjustment with slightly decreased phosphor removal rate with increasing recycling number, which proved the recyclability of Fe3O4@ SiO2@ Al2O3. nH2O and thereby its potential in recycling of phosphor resources. PMID- 27548968 TI - [Occurrence and Removal of Polycyclic Aromatic Hydrocarbons and Their Derivatives in Typical Wastewater Treatment Plants in Beijing]. AB - Substituted polycyclic aromatic hydrocarbons (SPAHs) can be emitted to the environment not only through the incomplete combustion, but also through the transformation from parent polycyclic aromatic hydrocarbons (PAHs) by photo chemical and biological processes. The toxicities of some SPAHs are higher than their corresponding PAHs. Samples were collected from the wastewater treatment plants in Beijing. Three types of SPAHs, including oxy-PAHs (OPAHs), methyl-PAHs (MPAHs) and nitro-PAHs (NPAHs), as well as 16 PAHs were analyzed, in order to study the occurrence and behavior of these compounds during the wastewater biological treatment process. MPAHs, OPAHs and PAHs were detected in the influent and effluent, but no NPAHs. The concentrations of PAHs in the influent in both the aquatic and particulate phases ranged from 1.94 to 4.34 ug . L-1, and SPAHs from 1.16 to 2.20 ug . L-1. The concentrations of PAHs in the effluent were between 0.77 and 0.98 ug . L-1, and SPAHs from 0.39 to 0.45 ug . L-1. The concentrations of the MPAHs were lower than their corresponding PAHs, while OPAHs were higher. The removal efficiencies of all the compounds ranged from 53% to 83%. PAHs and SPAHs were mainly removed by adsorption and biodegradation during the activated sludge treatment processes. Some OPAHs could be transformed from PAHs, and could be accumulated. The PAHs were mainly originated from incomplete combustion of wood and coal, and some from combustion of petroleum, while only a little from the discharge of petroleum. The concentrations of PAHs and SPAHs in the effluent were higher in autumn than summer and winter. Most of the SPAHs and PAHs were discharged to the agriculture area through the river-water irrigation, which might pose potential risk to the humans. As a result, it is necessary to upgrade the wastewater treatment process to improve the removal efficiency of PAHs and SPAHs. PMID- 27548969 TI - [Spectral Characteristics of Dissolved Organic Matters in Reject Water from Wastewater Treatment Plants]. AB - Reject water generated from sludge thickening, dewatering and stabilization process contains high-content and complex dissolved organic matters (DOM). The spectral characteristics of DOM in the reject water were investigated by three dimensional excitation-emission matrix and Fourier transform infrared spectroscopy. Fluorescent DOM (FDOM) from reject water were decomposed into six components by parallel factor analysis, the protein-like C1 (275/355 nm), C4 (235/350 nm) and C6 (275/305 nm) and the humic-like C2 (250, 340/440 nm) , C3 (320/380 nm) and CS (250/465 nm). Soluble COD in the sludge thickening reject water was positively correlated with all the three humic-like substances at P < 0.01 level, and was insignificantly influenced by protein-like substances. The tryptophan-like C1, C4 and humic-like CS increased in the centrifugal dewatering reject water (CDRW). FDOM in the advanced dewatering reject water (ADRW) were significantly different from those of other reject water in fluorescence peak locations and intensities, and humic-like C3 and tyrosine-like C6 in the DOM were 15.63 and 7.30 times higher than those in CDRW. Compared to sludge thickening reject water, infrared peaks related to polysaccharide and humic substances in CDRW were enhanced and massive proteins were released into ADRW. DOM structures in ADRW were changed owing to the complexation between metals and both humic substances and proteins. PMID- 27548970 TI - [Feasibility and Economic Analysis of Denitrification of Photovoltaic Wastewater Containing High Fluorine]. AB - In order to reduce acid and alkali dosing in wastewater treatment process of polycrystalline silicon by using denitrification after fluoride removal. This experiment studied the feasibility of first removing nitrogen using the denitrification process by start-up denitrifying reactor before fluoride removal. The results showed that the F- concentration in the waste water to had a certain influence on the denitrification. When the concentration of F- was controlled to about 750 mg . L-1, the activity of denitrifying bacteria was not significantly influenced; when the concentration of F- continued to increase, the denitrification efficiency of denitrifying sludge gradually reduced. In wastewater treatment of polycrystalline silicon, if the concentration of F- was kept below 800 mg . L-1, the denitrification performance of denitrifying sludge was not obviously affected. After 93 d operation, the total nitrogen in effluent was stabilized below 50 mg . L-1, the total nitrogen removal efficiency reached 90%, and the removal rate reached 5 kg . (m3 . d)-1. The calculation result showed, compared with the conventional denitrification process after fluoride removal, the proposed process could save about 70% of acid and 100% of alkali dosing, greatly reducing the cost of wastewater treatment. PMID- 27548971 TI - [Quick Start-up and Sustaining of Shortcut Nitrification in Continuous Flow Reactor]. AB - How to achieve fast and stable startup of shortcut nitrification has a very important practical value for treatment of low C/N ratio wastewater. Thus, the quick start-up and sustaining of shortcut nitrification were investigated in continuous flow reactor targeting at the current situation of urban wastewater treatment plant using a continuous flow process. The results showed that quick start-up of shortcut nitrification could be successfully achieved in a continuous flow reactor after 60 days' operation with intermittent aeration and controlling of three stages of stop/aeration time (15 min/45 min, 45 min/45 min and 30 min/30 min). The nitrification rates could reach 90% or 95% respectively, while influent ammonia concentrations were 50 or 100 mg . L-1 with stop/aeration time of 30 min/30 min. In addition, intermittent aeration could inhibit the activity of nitrite oxidizing bacteria (NOB), while short hydraulic retention time (HRT) may wash out NOB. And a combined use of both measures was beneficial to sustain shortcut nitrification. PMID- 27548972 TI - [Performance Recoverability of Denitrifying Granular Sludge Under the Stressing Effect of Nanoscale Zero-valent Iron]. AB - To explore the potential stressing effect of nanoscale zero-valent iron (nZVI) on denitrifying granular sludge (DGS), the evolution of DGS denitrifying performance under different C/N ratios was investigated in this study, by carrying out batch tests of eight successive periods with the nZVI shock-loading. The results showed that the specific denitrification rate of u value decreased when the nZVI dosage was higher than 5 mg . L-1. Meanwhile, a positive correlation between the inhibition ratio (IR) of u value and substrate C/N ratios or nZVI dosage was observed. When the nZVI dosage reached 100 mg . L-1, both extracellular protein and polysaccharides concentrations decreased obviously. It would be beneficial to promote the recovery of DGS denitrifying activity and reduce the COD demanding to remove unit mass of nitrate, by increasing external carbon source with C/N ratios of higher than 4. On the basis of Freundlich and Langmuir adsorption isotherms, when higher C/N ratio was provided, stronger bioadsorption of nZVI would be achieved. During the recovery period, a significant improvement of DCS denitrifying performance under the high C/N ratio was expected, due to the continuous washout of total iron in sludge phase (Qe), while the u value would reach or approach the one of the control group when Qe was lower than 0.4 mg . g 1. PMID- 27548973 TI - [Effect of Low-concentration Ciprofloxacin on the Nitrification and Nitrifying Microorganisms of Biofilms in Biological Aerated Filter]. AB - Effect of low-concentration ciprofloxacin (CIP) on nitrification and nitrifying microorganisms of biofilms was studied in biological aerated filters (BAF). Quantitative PCR (qPCR) was used to determine the abundance variance of four ciprofloxacin resistance genes (CIP-ARGs) during nitrification in biofilms. The correlations between the abundances of CIP-ARGs and nitrifying microorganisms were also discussed. The results showed that CIP had little influence on the ammonium oxidation process of biofilm microorganisms, whereas inhibition of the nitrite oxidation process was found. The quantitative results of ammonium oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) including Nitrobacter and Nitrospira indicated that the inhibition on the transformation of nitrite was resulted from the inhibition on Nitrobacter and Nitrospira. In addition, little influence of CIP on the relative abundance of aac and qepA in biofilms was found, but the influence on parC and oqxB was great. The abundance of Nitrotacter exhibited significant positive correlation with the abundance of parC. Similar significant correlation was also found between the abundances of Nitrospira and oqxB. It could be speculated that the genetic elements of different nitrifying microorganisms in biofilms possibly carried CIP-ARGs. PMID- 27548974 TI - [Optimization Study on the Nitrogen and Phosphorus Removal of Modified Two- sludge System Under the Condition of Low Carbon Source]. AB - This paper explored the method of resolving insufficient carbon source in urban sewage by comparing and analyzing denitrification and phosphorus removal (NPR) effect between modified two-sludge system and traditional anaerobic-aerobic anoxic process under the condition of low carbon source wastewater. The modified two-sludge system was the experimental reactor, which was optimized by adding two stages of micro-aeration (aeration rate 0.5 L . mm-1) in the anoxic period of the original two-sludge system, and multi-stage anaerobic-aerobic-anoxic SBR was the control reactor. When the influent COD, ammonia nitrogen, SOP concentration were respectively 200, 35, 10 mg . L-1, the NPR effect of the experimental reactor was hetter than that of thecontrol reactor with the removal efficiency of TN being 94.8% vs 60.9%, and TP removal being 96.5% vs 75%, respectively. The effluent SOP, ammonia, TN concentration of the experimental reactor were 0.35, 0.50, 1.82 mg . L-1, respectively, which could fully meet the first class of A standard of the Pollutants Emission Standard of Urban Wastewater Treatment Firm (GB 18918 2002). Using the optimized treatment process, the largest amounts of nitrogen and phosphorus removal per unit carbon source (as COD) were 0.17 g . g-1 and 0.048 g . g-1 respectively, which could furthest solve the lower carbon concentration in current municipal wastewater. PMID- 27548975 TI - [Effects of Short-time Conservation Tillage Managements on Greenhouse Gases Emissions from Soybean-Winter Wheat Rotation System]. AB - Field experiments including one soybean growing season and one winter-wheat growing season were adopted. The experimental field was divided into four equal area sub-blocks which differed from each other only in tillage managements, which were conventional tillage (T) , no-tillage with no straw cover ( NT) , conventional tillage with straw cover (TS) , and no-tillage with straw cover (NTS). CO2 and N2O emission fluxes from soil-crop system were measured by static chamber-gas chromatograph technique. The results showed that: compared with T, in the soybean growing season, NTS significantly increased the cumulative amount of CO2 (CAC) from soil-soybean system by 27.9% (P = 0.045) during the flowering podding stage, while NT significantly declined CAC by 28.9% (P = 0.043) during the grain filling-maturity stage. Compared with T, NT significantly declined the cumulative amount of N2O (CAN) by 28.3% (P = 0.042) during the grain filling maturity stage. In the winter-wheat growing season, compared with T, TS and NT significantly declined CAC by 24.3% (P = 0.032) and 36.0% (P = 0.041) during the elongation-booting stage, and also declined CAC by 26.8% (P = 0.027) and 33.1% (P = 0.038) during the maturity stage. During the turning-green stage, compared with T treatment, NT, NTS, and TS treatments had no significant effect on CAN, while NTS significant declined CAN by 42.0% (P = 0.035) compared with NT. Our findings suggested that conservation tillage managements had a more significant impact on CO2 emission than 20 emission from soil-crop system. PMID- 27548976 TI - [Diurnal and Seasonal Dynamic Variation of Soil Respiration and Its Influencing Factors of Different Fenced Enclosure Years in Desert Steppec]. AB - The fenced measures could improve the ecological environment of degraded grassland, it's a main measure for restoration of degraded grassland vegetation in China. Soil respiration (Rs) is an important component of an ecosystem's carbon cycle and the main pathway for carbon moving from the ecosystem to the atmosphere. In order to explore soil respiration characteristics and influencing factors of the different fenced years in arid desert grassland, we continuously observed Rs rate and environmental factors in the growing season of fenced enclosure 11a, 7a and no fenced (CK) desert steppe in Ningxia. The results showed that: (1) Both the diurnal andseasonal variations of Rs rate showed a single asymmetric peak changing in fenced enclosure of 11 years, 7 years, CK desert steppe. On the daily scale, the maximum and minimum values of Rs rate were found in the periods of 12:00-16:00 and 00:00-06:00,respectively. On the seasonal variation scale, the maximum value of Rs rate occurred in August with suitable precipitation and temperature conditions. And the Rs rate of the growing season of different fenced enclosure years was in the order of 11a [0.143 g . (m2 . h) 1] > 7a [0.138 g . (m2 . h)-1] > CK [0.106 g . (m2 - h)-1]. (2) According to statistical analysis, it indicated that R2 rate had a significant exponential positive relationship with air and soil temperature in fenced enclosure of 11 years, 7 years, CK desert steppe (P < 0.01). The order of the correlation of Rs rate and temperature was shown as soil surface temperature (R2: 0.408-0.413) > air temperature (R2: 0.355-0.376) > 5-20 cm soil temperature (R2: 0.263-0.394). The temperature sensitivity coefficient Q, increased gradually with the soil depth, and Q1, of different fenced enclosure years was showed as 11 a (2.728) > 7a (2.436) > CK (2.086). (3) A significant quadratic function model (P < 0.05) was observed for the relationship between Rs rate and relative air humidity, soil moisture content of fenced enclosure 11a, 7a and CK desert steppe in the whole growing season. Rs rate had a significant linear negative correlation with air carbon dioxide concentration (P < 0.01), a linear positive correlation with the windspeed (P < 0.05), and a significant weak linear positive correlation with light intensity (P < 0.01). (4) It showed that Rs increasedwith increasing fenced closure years in arid desert steppe, and temperature sensitivity coefficient Q10 also increased with increasing fenced enclosure years. To sum up, 0-20 cm soil temperature and moisture were the main influencing factors of soil respiration of desert steppe. This study has important implications to understand the role that different fenced enclosure years play in carbon emission. Such information will lay a foundation for assessing carbon source or carbon sequestration of different fenced enclosure years in desert steppe. Therefore, our research results have important function for better managing grassland in desert steppe in Ningxia and other arid and semiarid areas of North China. PMID- 27548977 TI - [Correlation Among Soil Organic Carbon, Soil Inorganic Carbon and the Environmental Factors in a Typical Oasis in the Southern Edge of the Tarim Basin]. AB - We analyzed the differentiation among the environmental factors and soil organic/inorganic carbon contents of irrigated desert soil, brown desert soil, saline soil and aeolian sandy soil by classical statistics methods, and studied the correlation between soil carbon contents and the environmental factor by redundancy analysis (RDA) in a typical oasis of Yutian in the southern edge of the Tarim Basin. The results showed that the average contents of soil organic carbon and soil inorganic carbon were 2.51 g . kg-1 and 25.63 g . kg-1 respectively. The soil organic carbon content of the irrigated desert soil was significantly higher than those of brown desert soil, saline soil and aeolian sandy soil, while the inorganic carbon content of aeolian sandy soil was significantly higher than those of other soil types. The soil moisture and nutrient content were the highest in the irrigated desert soil and the lowest in the aeolian sandy sail. All soil types had high degree of salinization except the irrigated desert soil. The RDA results showed that the impacts of environmental factors on soil carbon contents ranked in order of importance were total nitrogen > available phosphorus > soil moisture > ground water depth > available potassium > pH > total salt. The soil carbon contents correlated extremely significantly with total nitrogen, available phosphorus, soil moisture and ground water depth (P < 0.01), and it correlated significantly with available potassium and pH (P < 0.05). There was no significant correlation between soil carbon contents and other environmental factors (P > 0.05). PMID- 27548978 TI - [Effects of Low-Molecular-Weight Organic Acids on the Speciation of Pb in Purple Soil and Soil Solution]. AB - Lead (Pb) in purple soil was selected as the research target, using one-step extraction method with 0.01 mol . L-1 sodium nitrate as the background electrolyte to study the release effect of citric acid (CA), tartaric acid (TA) and acetic acid (AC) with different concentrations. Sequential extraction and geochemical model (Visual Minteq v3.0) were applied to analyze and predict the speciation of Pb in soil solid phase and soil solution phase. Then the ebvironmental implications and risks of low-molecule weight organic acid (LMWOA) on soil Pb were analyzed. The results indicated that all three types of LMWOA increased the desorption capacity of Pb in purple soil, and the effect followed the descending order of CA > TA > AC. After the action of LMWOAs, the exchangeable Pb increased; the carbonate-bound Pb and Fe-Mn oxide bound Pb dropped in soil solid phase. Organic bound Pb was the main speciation in soil solution phase, accounting for 45.16%-75.05%. The following speciation of Pb in soil solution was free Pb, accounting for 22.71%-50.25%. For CA and TA treatments, free Pb ions and inorganic bound Pb in soil solution increased with increasing LMWOAs concentration, while organic bound Pb suffered a decrease in this process. An opposite trend for AC treatment was observed compared with CA and TA treatments. Overall, LMWOAs boosted the bioavailability of Pb in purple soil and had a potential risk to contaminate underground water. Among the three LMWOAs in this study, CA had the largest potential to activate soil Pb. PMID- 27548979 TI - [Phytoremediation of Petroleum Contaminated Soils with Iris pseudacorus L. and the Metabolic Analysis in Roots]. AB - In this study, we performed a greenhouse pot-culture experiment to investigate the potential of a wild ornamental plant Iris pseudacorus L. in remediating petroleum contaminated soils from the Dagang Oilfield in Tianjin, China. The results suggested that Iris pseudacorus L. had great resistance to <= 40,000 mg . kg(-1 of total petroleum hydrocarbons (TPHs). The removal rate of TPHs with concentrations of 10,000 mg . kg-1, 20,000 mg . kg-1 and 40,000 mg . kg-1 in soils by Iris pseudacorus L. was 42.1%, 33.1% 31.2%, respectively, much higher than those in the corresponding controls (31.8%, 21.3% 11.9%, respectively) (P < 0.05). The root specific surface area of Iris pseudacorus L. was determined by the root scanner. The results suggested that TPHs with concentrations of 10,000 mg . kg-1, 20,000 mg . kg-1 and 40,000 mg . kg-1 in soils increased the root specific surface area comparing with the controls. Additionally, the metabolic analysis showed that root metabolism changed to different degrees under the stress of TPHs, and the levels or species of metabolites had a significant change (P < 0.001). Furthermore, the results showed that 5 of 11 metabolites (VIP value > 1.2) with the root specific surface area from the PLS-DA model analysis, including ethanedioic acid, lactic acid, 2-butenedioic acid, phosphate and propanedioic acid, were positively correlated with the root specific surface area, but the others, gluconic acid, uridine, butanoic acid, maltose, 9,12 octadecadienoic acid, phenylalanine, were negatively correlated with it. In conclusion, using Iris pseudacorus L. to remediate petroleum contaminated soils is feasible, and the metabolic analysis in roots is useful to better understand the metabolic response of plants exposure to petroleum contaminated soils, and then reveals its remediated mechanisms. PMID- 27548980 TI - [Oxidation Process of Dissolvable Sulfide by Manganite and Its Influencing Factors]. AB - As one of the manganese oxides, which are easily generated and widely distributed in supergene environment, manganite participates in the oxidation of dissolvable sulfide (S2-), and affects the migration, transformation, and the fate of sulfides. In the present work, the redox mechanism was studied by determining the intermediates, and the influence of initial pH and oxygen atmosphere on the processes were studied. The chemical composition, crystal structures and micromorphologies were characterized by XRD, FTIR and TEM. The concentration of S2- and its oxidation products were analyzed using spectrophotometer, high performance liquid chromatograph and ion chromatograph. The results indicated that elemental sulfur was formed as the major oxidation product of S2- oxidation, and decreased pH could accelerate the oxidation rate of S2- in the initial stage, however, there was no significant influence on final products. Elemental S could be further oxidized to S2O32- when the reaction system was bubbled with oxygen, and manganite exhibited excellent catalytic performance and chemical stability during the oxidation of dissolvable sulfide by oxygen. After reaction of more than 10 h, the crystal structure of manganite remained stable. PMID- 27548981 TI - [Screening and Enzyme Production Characteristics of Thermophilic Cellulase producing Strains]. AB - A total of 6 thermophilic cellulase-producing strainswere isolated from organic garden waste mixed chicken composting at thermophilic period. These isolates were identified as Streptomyces thermoviolaceus, S. thermodiastaticus, S. thermocarboxydus, S. albidoflavus, S. thermovulgaris and Brevibacillus borstelensis through 16S rRNA gene sequence alignment and phylogenetic tree analysis. The cellulose-degrading microbial community has been investigated in few researches so far both at home and abroad. In this study, the mixed strains M 1 was made up of the 6 cellulose-decomposing microorganisms. The CMCase activity of the mixed strains M- 1 was stronger than any of the 6 single strains. Production of CMCase from mixed strains M-1 was studied by optimizing different physico-chemical parameters. The Maximum CMCase production (135.9 U . mL-1) of strains M-1 was achieved at 45 degrees C in a liquid medium (pH 4) inoculated with 1% (volume fraction), containing a mixture of wheat bran and starch, corn flour and KNO3. After optimization of separation conditions, CMCase production capacity was improved by 1.8 times. PMID- 27548982 TI - [Development of Determination Method of Fluoroquinolone Antibiotics in Sludge Based on Solid Phase Extraction and HPLC-Fluorescence Detection Analysis]. AB - Fluoroquinolone antibiotics (FQs), as the common pharmaceuticals and personal care products (PPCPs), are widespread in the environment. FQs contained in wastewater would be ultimately enriched in sludge, posing a potential threat to the consequent sludge utilization. To optimize the analytical method applicable to the determination of FQs in sludge, the authors selected ofloxacin (OFL), norfioxacin (NOR), ciprofloxacin (CIP) and lomefloxacin (LOM) as the target FQs, and established a method which was based on cell lysis, FQs extraction with triethylamine/methanol/water solution, Solid Phase Extraction (SPE) and HPLC Fluorescence Detection (FLD) determination. After the investigation, phosphoric acid-triethylamine was decided to be the buffer salt, and methanol was chosen as the organic mobile phase. The gradient fluorescence scanning strategy was proved to be necessary for the optimal detection as well. Furthermore, by the designed orthogonal experiments, the effects of the extraction materials, pH, and the eluents on the efficiency of SPE extraction were evaluated, by which the optimal extraction conditions were determined. As a result, FQs in liquid samples could be analyzed by utilizing HLB extraction cartridge, and the recovery rates of the four FQs were in the range of 82%-103%. As for solid samples, the recovery rates of the four FQs contained reached up to 71%-101%. Finally, the adsorptivity of the sludge from the different tanks ( anaerobic, anoxic and oxic tanks) was investigated, showing gradual decrease in the adsorption capacity, but all adsorbed over 90% of the EQs. This conclusion also confirmed that 50% removal of FQs in the domestic wastewater treatment plant was realized by sludge adsorption. PMID- 27548983 TI - [Distribution and Risk Assessment of Sulfonamides Antibiotics in Soil and Vegetables from Feedlot Livestock]. AB - Soil and vegetable samples were collected from 13 different livestock farms of different sizes in Xinxiang of China, and the residues of three sulfonamides including sulfadiazine, sulfamonomethoxine, and sulfamethoxazole were analyzed by HPLC with a fluorimetric detector, The results indicated that the total concentration ranges of the three sulfonamides in soil and vegetable were 7.60 176.26 ug . kg-1 and ND-32, 70 ug . kg-1, respectively. The mean concentrations were 70.73 ug . kg-1 and 7.08 ug . kg-1 for soil and vegetables. The residue levels in soil were all lower than the ecotoxic effect trigger value (100 ug . kg 1) set by the Veterinary Medicine International Coordination Commission, indicating the low risk for organisms in soil. The concentrations of three sulfonamides varied significantly in different kinds of vegetables and were all lower than the acceptable daily intake values [50 ug . (kg .d)-1] set by Joint FAO/WHO Expert CommIttee on Food Additives. But we cannot neglect the potential ecotoxicity and resistance for human via food chain. PMID- 27548984 TI - [Influence of Four Kinds of PPCPs on Micronucleus Rate of the Root-Tip Cells of Vicia-faba and Garlic]. AB - In order to determine the degree of biological genetic injury induced by PPCPs, the genotoxic effects of the doxycycline (DOX), ciprofloxacin (CIP), triclocarban (TCC) and carbamazepine (CBZ) in the concentration range of 12.5-100 mg . L-1 were studied using micronucleus rate and micronucleus index of Vicia-fabe and garlic. The results showed that: (1) When the Vicia-faba root- tip cells were exposed to DOX, CIP, TCC and CBZ, micronucleus rates were higher than 1.67 0/00 (CK1), it was significantly different from that of the control group (P < 0.05), and the micronucleus index was even greater than 3.5; With the increasing concentrations of the PPCPs, the micronucleus rates first increased and then decreased. (2) When the garlic root tip cells were exposed to DOX, CIP, TCC and CBZ respectively, the micronucleus rates were less than those of the Vicia-faba, while in most treatments significantly higher than that of the control group (0.670/00). The micronucleus index was higher than 3.5 in the groups exposed to CIP with concentrations of 25, 50, 100 mg . L-1 and TCC and CBZ with concentrations of 25 mg . L-1; With the increase of exposure concentrations, the micronucleus rate showed a trend of first increasing and then decreasing as well. (3) Under the same experimental conditions, the cells micronucleus rates of the garlic cells caused by the four tested compounds were significantly lower than those of Vicia-faba. (4) The micronucleus index of the root tip cells of Vicia faba and garlic treated with the four kinds of compounds followed the order of CIP > CBZ > TCC > DOX. These results demonstrated that the four compounds caused biological genetic injury to root-tip cells of Vicia-faba and garlic, and the genetic damage caused to garlic was significantly lower than that to Vicia-faba. The damages caused by the four kinds of different compounds were also different. PMID- 27548985 TI - [Environmental Behaviors and Ecotoxicology of the Emerging Contaminants Polyhalogenated Carbazoles]. AB - Polyhalogenated carbazoles (PHCs), with a complex chemical structure similar to polychlorinated dibenzofurans, are a class of emerging environmental organic contaminants. There are 135 congeners for PHCs with a pure halogenation. Most of PHCs are not man-made products. Although PHCs in the environment were firstly discovered in the 1980s, these emerging halogenated compounds were not seriously considered until recent years. Recently, more than 20 PHCs have been detected in sediment and soil samples. In addition, studies have shown that PHCs exhibited dioxin-like toxicity and were persistent and bioaccumulative. Therefore, it is very important to understand the distribution, origins and ecotoxicology of PHCs for a better assessment of their environmental risks. To date, research on the environmental behaviors of PHCs is relatively limited and warrants further investigations. In this review, the environmental distribution, source, analytical methods and toxicity of PHCs were summarized and future research needs were outlined. PMID- 27548986 TI - [Classification of Priority Area for Soil Environmental Protection Around Water Sources: Method Proposed and Case Demonstration]. AB - Based on comprehensive consideration of soil environmental quality, pollution status of river, environmental vulnerability and the stress of pollution sources, a technical method was established for classification of priority area of soil environmental protection around the river-style water sources. Shunde channel as an important drinking water sources of Foshan City, Guangdong province, was studied as a case, of which the classification evaluation system was set up. In detail, several evaluation factors were selected according to the local conditions of nature, society and economy, including the pollution degree of heavy metals in soil and sediment, soil characteristics, groundwater sensitivity, vegetation coverage, the type and location of pollution sources. Data information was mainly obtained by means of field survey, sampling analysis, and remote sensing interpretation. Afterwards, Analytical Hierarchy Process (AHP) was adopted to decide the weight of each factor. The basic spatial data layers were set up respectively and overlaid based on the weighted summation assessment model in Geographical Information System (GIS), resulting in a classification map of soil environmental protection level in priority area of Shunde channel. Accordingly, the area was classified to three levels named as polluted zone, risky zone and safe zone, which respectively accounted for 6.37%, 60.90% and 32.73% of the whole study area. Polluted zone and risky zone were mainly distributed in Lecong, Longjiang and Leliu towns, with pollutants mainly resulted from the long-term development of aquaculture and the industries containing furniture, plastic constructional materials and textile and clothing. In accordance with the main pollution sources of soil, targeted and differentiated strategies were put forward. The newly established evaluation method could be referenced for the protection and sustainable utilization of soil environment around the water sources. PMID- 27548987 TI - [Not Available]. PMID- 27548988 TI - [HEALTH, WELLBEING AND CONVIVIALITY OF THE ELDERLY. THE PORTUGUESE, SPANISH AND EUROPEAN SITUATION]. AB - OBJECTIVE: To characterize the specificities of aging in Portugal and Spain, in contrast to the reality of nineteen countries of the European Union. METHODOLOGY: The senior condition is characterized in different dimensions: health status, the level of wellbeing, conviviality and sense of loneliness. For that we have analyzed the results of the European Social Survey, round 5. RESULTS: In Portugal, compared to Spain, it has been identified in the elderly population: greater financial difficulties, poorer perceived health status and wellbeing but, simultaneously, less limitation in performing activities of daily life. Respecting to con- viviality, Portugal and Spain are distinct from other populations of the European reality analyzed, with a high frequency of con- vivial activities. CONCLUSION: In conclusion it was found the existence of national characteristics that suggest the existence of social and cultural factors that determine the experience of aging. PMID- 27548989 TI - [EMOTIONAL DISORDERS IN CHILDREN VICTIMS OF NATURAL DISASTERS]. AB - The effects of disasters on physical health tend to be well-known, with short, medium and long term sequelae. On the other hand, not always is have recognized in the same way the effects on mental health, despite having shown that, in situations of disaster or catastrophe there is a psychological signs of suffering increase and increases to a certain extent the psychiatric morbidity and other problem social. It is estimated that between a third and half of the exposed population, it suffers from some psychological manifestation. It has been erroneously thought that children and adolescents, not suffering with the same intensity of especially traumatic situations. In fact it was presumed, given their reactions so different from that of adults, had some protection. Currently, this has denied and minors are considered to be a group of high risk in cases of disasters and emergencies. Investigations carried out, demonstrate that in children and adolescents, the psychological sequels tend to be frequent and affect directly to the physical, mental and social development. Natural disasters are unexpected situations that will produce a serie of emotional reactions of diverse severity in their survivors, especially children, one of the most vulnerable groups due to a less understanding of what happened and difficulty expressing what they feel, having a personality still developing, and so directly affecting their physical, mental and social development. Therefore suffering the emotional scars, they will take longer to resolve and have a lifetime to live with them. These consequences should be treated by a corresponding community nurse and sometimes, depending on the severity and persistence (more than 3 months), a referral will be made to a qualified mental health professional, taking into account a number of recommendation and assesment canons. Parents or tutors with health professionals have an important role in the recovery of their children and their reactions will be very influenced by these firts. In recent years the interest has increased by the impact of the disaster on the mental health of affected populations and currently has become evident the need for a comprehensive approach that transcends disease care and repair of material damage. PMID- 27548990 TI - [TECHNOPATHOLOGY: THE NEW EPIDEMIC OF THE 21ST CENTURY]. AB - The new technologies have brought with them a change in the way of communication. The access to information through the Internet is continuous, to the point that, in some cases, it has become into an addiction. Through this article, we would try to analyze from the biologic point of view as the psychological and social ones, the pathologies that have emerged due to the excessive use of the ICTs. PMID- 27548991 TI - [THE GIFT OF THE APPLICATION OF REIKI THERAPY IN CANCER PATIENTS]. AB - Pain is one of the most feared symptoms of cancer. Bad pain not properly relieved contributes to the suffering of the patient and family. This may encourage them to seek additional complementary and alternative therapies, such as the one in our literature review. Reiki is understood as a healing method that uses universal energy to achieve balance and harmony of body, mind and soul, through the laying on of hands. Reiki is a relatively new the rapyin relation to the relief of the symptoms of cancer. In fact, there are still a few articles in this field. Currently, the authors explore the evidence on the effectiveness of Reiki in relation to cancer pain and symptom control. Due to the increased interest deposited in Reiki by the health professionals--especially for oncology professionals--to relieve the symptoms of cancer, there has been a synthesis of recent studies to provide the evidence so far. After our literature review, we can conclude that there is insufficient evidence on the effectiveness of Reiki in relieving the cancer's symptoms due to the small sample size used, the paucity of studies and the abandonment of the study participants and others. PMID- 27548992 TI - [CONSEQUENCES OF FALLS IN A GERIATRIC NURSING CENTER FOR VALID. DESCRIPTIVE STUDY]. AB - OBJECTIVE: To address the immediate consequences produced in the falls suffered by valid institutionalized elderly population' in the last twelve months. METHOD: A cross sectional study, by personal interview. Simple random sampling was performed. The study area corresponded to a private nursing home. The measuring instruments used in the study were the Mini Mental State Examination Lobo (MEC 35, 1979) to initially assess the level of cognitive development elderly study participants, and the WHO questionnaire for the study of falls in the elder 1989. RESULTS: Of the 21 drops produced in the last twelve months was found that 61.9% of falls were female, compared to 38.1% who relapsed in males. 52.4% of falls are not caused any consequences. 28.6% of falls caused superficial injuries and/or bruises, while the proportion of fractures corresponded to 19% for both sexes. Most of the falls did not produce immediate consequences whose percentage was 52.4% of cases. Second are superficial wounds and/or bruises with 28.6% and finally fractures with a ratio of 19%. CONCLUSIONS: The investigators considered the necessity of involvement of health professionals and the implementation ofpreventive strategies that can reduce the prevalence of falls. Thiswill successfully improve the quality of life of the elderly. PMID- 27548994 TI - [Not Available]. PMID- 27548993 TI - [AVOID COMMON MISTAKES IN REALIZATION OF A ELECTROCARDIOGRAM]. AB - INTRODUCTION: The electrocardiogram (ECG) is a noninvasive technique to perform simple, economical, reproducible and provides valuable information that can be used to make the diagnosis of the patient and to guide clinical decisions. It is a diagnostic test used frequently as it can be done quickly, since it is done with a laptop and generally is always possible implementation in any field either primary care, specialty outpatient care. The diagnosis made by the ECG is considered valid in clinical practice, but is only effective if the electrodes are placed in the correct anatomical locations, if the hoses are properly attached to the electrodes, the registry maintains a good quality (the filters are used appropriate, interference and electrical noise are avoided) and ECG compares made by the same registration system (ECG 5 or 10 lead) for determining evolutionary changes (to determine changes in the ST segment during myocardial ischemia or assess the changes caused by reperfusion therapies). OBJECTIVE: To review the most common errors in electrocardiography, which are related to inappropriate placements of shunts, cross or exchange of patch cords limb leads, records of poor quality and comparisons of ECG serials made with different acquisition systems (10 vs 5 lead). CONCLUSIONS: We make the recommendations to prevent and avoid these scams that can lead to diagnosis and treatment with adverse outcomes for the patient. PMID- 27548995 TI - Elevating glucose and insulin secretion by carbohydrate formulation diets in late lactation to improve post-weaning fertility in primiparous sows. AB - Primiparous (P1) sows commonly lose excessive body reserves to meet energy requirements for maintenance and milk production during lactation, and consequently, post-weaning reproductive performance may be compromised. The present studies determined whether ad libitum feeding a glucogenic carbohydrate diet (CHO) during late lactation could stimulate insulin and glucose secretion (experiment 1) and improve subsequent litter size (experiment 2). For experiment 1, 15 P1 sows, and for experiment 2, 99 P1 sows (198.5 +/- 2.7 kg) were allocated randomly according to suckled litter size (>=10 piglets), either to a CHO diet (14.3 MJ DE/kg, 19.8% crude protein) or a standard lactation diet (control; 14.2 DE MJ/kg, 19.5% crude protein) at 8 days before weaning. The CHO diet aimed to provide glucogenic content (extruded wheat, dextrose and sugar) as energy sources instead of fat sources without changing total dietary energy. Pre-prandial plasma glucose and insulin concentrations were not influenced by treatments. However, post-prandial plasma glucose and insulin concentrations and their peaks were both higher (p < .05) compared to the control treatment. Body weight loss during lactation was relatively low at 3%-4% for both treatments and did not differ between control and CHO treatments (-7.6 +/- 1.6 vs -5.4 +/- 1.2 kg; p > .05). Second litter size was not influenced by diet (p > .05), but the weaning-to mating interval was shorter in CHO sows (p < .05). This study demonstrates that providing an enriched CHO diet in late lactation did influence post-weaning follicle growth but did not improve subsequent litter size. This may be due to the primiparous sows in this study not experiencing severe negative energy balance and there was no second litter syndrome in this farm which limited the ability of diet to improve sow fertility. PMID- 27548996 TI - Self-rated health and cancer risk - a prospective cohort study among Danish women. AB - BACKGROUND: Self-rated health (SRH) has been shown to be a strong predictor of mortality from a number of major chronic diseases, however, the association with cancer remains unclear. The aim of this study was to investigate a possible association between change in SRH and cancer incidence. MATERIALS AND METHODS: SRH and information on lifestyle and other risk factors were obtained for 13-636 women in the Danish Nurse Cohort. Cancers that developed during 12 years of follow-up were identified in the National Patient Registry. An association between SRH and cancer was examined in a Cox proportional hazards model with adjustment for age, smoking, alcohol, marital status, physical activity, body mass index and estrogen replacement therapy. RESULTS: No significant association was found between SRH and overall cancer incidence in the age-adjusted Cox proportional hazards model (1.04; 95% CI 0.93-1.16), even after adjustment for potential confounding factors (HR 1.08; 95% CI 0.96-1.21). Likewise, there was no significant association between SRH and breast cancer (HR 1.09; 95% CI 0.89 1.33), lung cancer (HR 1.03; 95% CI 0.71-1.49) or colon cancer (HR 1.08; 95% CI 0.75-1.54). CONCLUSION: SRH is not significantly associated with the incidence of all cancers or breast, lung or colon cancer among Danish female nurses. Women who reported a decrease in SRH between 1993 and 1999 had the same risk for cancer as those who reported unchanged or improved SRH. PMID- 27548997 TI - Beneficial effects of neuropeptide galanin on reinstatement of exercise-induced somatic and psychological trauma. AB - Galanin is a versatile neuropeptide that is distinctly upregulated by exercise in exercise-related tissues. Although benefits from exercise-induced upregulation of this peptide have been identified, many issues require additional exploration. This Review summarizes the information currently available on the relationship between galanin and exercise-induced physical and psychological damage. On the one hand, body movement, exercise damage, and exercise-induced stress and pain significantly increase local and circulatory galanin levels. On the other hand, galanin plays an exercise-protective role to inhibit the flexor reflex and prevent excessive movement of skeletal muscles through enhancing response threshold and reducing acetylcholine release. Additionally, elevated galanin levels can boost repair of the exercise-induced damage in exercise-related tissues, including peripheral nerve, skeletal muscle, blood vessel, skin, bone, articulation, and ligament. Moreover, elevated galanin levels may serve as effective signals to buffer sport-induced stress and pain via inhibiting nociceptive signal transmission and enhancing pain threshold. This Review deepens our understanding of the profitable roles of galanin in exercise protection, exercise injury repair, and exercise-induced stress and pain. Galanin and its agonists may be used to develop a novel preventive and therapeutic strategy to prevent and treat exercise-induced somatic and psychological trauma. (c) 2016 Wiley Periodicals, Inc. PMID- 27548998 TI - New approach in the treatment of refractory vitiligo: CO2 laser combined with betamethasone and salicylic acid solution. AB - The aim of this study is to evaluate the use of fractional carbon dioxide laser (CO2 ) with betamethasone and salicylic acid solution in the treatment of patients with refractory vitiligo in hands. Each hand of the patient was randomly assigned to one of two groups: lesion treated with fractional carbon dioxide laser associated with betamethasone and salicylic acid solution administration or lesion treated only with betamethasone and salicylic acid solution. We conclude that combined treatment with fractional carbon dioxide laser and betamethasone associated with salicylic acid solution could effectively and safely be used in the treatment of refractory vitiligo. PMID- 27548999 TI - Fate of Plutonium at a Former Nuclear Testing Site in Australia. AB - A series of the British nuclear tests conducted on mainland Australia between 1953 and 1963 dispersed long-lived radioactivity and nuclear weapons debris including plutonium (Pu), the legacy of which is a long-lasting source of radioactive contamination to the surrounding biosphere. A reliable assessment of the environmental impact of Pu contaminants and their implications for human health requires an understanding of their physical/chemical characteristics at the molecular scale. In this study, we identify the chemical form of the Pu remaining in the local soils at the Taranaki site, one of the former nuclear testing sites at Maralinga, South Australia. We herein reveal direct spectroscopic evidence that the Pu legacy remaining at the site exists as particulates of Pu(IV) oxyhydroxide compounds, a very concentrated and low soluble form of Pu, which will serve as ongoing radioactive sources far into the future. Gamma-ray spectrometry and X-ray fluorescence analysis on a collected Pu particle indicate that the Pu in the particle originated in the so-called "Minor trials" that involved the dispersal of weapon components by highly explosive chemicals, not in the nuclear explosion tests called "Major trials". A comprehensive analysis of the data acquired from X-ray fluorescence mapping (XFM), X-ray absorption near-edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) suggests that the collected Pu particle forms a "core-shell" structure with the Pu(IV) oxyhydroxide core surrounded by an external layer containing Ca, Fe, and U, which further helps us to deduce a possible scenario of the physical/chemical transformation of the original Pu materials dispersed in the semiarid environment at Maralinga more than 50 years ago. These findings also highlight the importance of the comprehensive physical/chemical characterization of Pu contaminants for reliable environmental- and radiotoxicological assessment. PMID- 27549000 TI - The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection. AB - BACKGROUND: Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy. AIM: To investigate the efficacy, tolerability and potential for drug-drug interactions (DDIs) of IFN-free treatment in patients aged >=65 years in a large real-world cohort. METHODS: A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir +/-ribavirin; daclatasvir/sofosbuvir +/-ribavirin; paritaprevir/ombitasvir +/-dasabuvir +/-ribavirin or simeprevir/sofosbuvir +/ ribavirin in genotype 1/4, and daclatasvir/sofosbuvir +/-ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged >=65 years (n = 137) of whom 41 patients were >=75 years. RESULTS: Sustained virological response rates were 98% and 91% in patients aged >=65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients >=65 years with cirrhosis (median, three per patient; range, 0-10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.). CONCLUSIONS: Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided. PMID- 27549001 TI - A Selection for Assembly Reveals That a Single Amino Acid Mutant of the Bacteriophage MS2 Coat Protein Forms a Smaller Virus-like Particle. AB - Virus-like particles are used to encapsulate drugs, imaging agents, enzymes, and other biologically active molecules in order to enhance their function. However, the size of most virus-like particles is inflexible, precluding the design of appropriately sized containers for different applications. Here, we describe a chromatographic selection for virus-like particle assembly. Using this selection, we identified a single amino acid substitution to the coat protein of bacteriophage MS2 that mediates a uniform switch in particle geometry from T = 3 to T = 1 icosahedral symmetry. The resulting smaller particle retains the ability to be disassembled and reassembled in vitro and to be chemically modified to load cargo into its interior cavity. The pair of 27 and 17 nm MS2 particles will allow direct examination of the effect of size on function in established applications of virus-like particles, including drug delivery and imaging. PMID- 27549002 TI - [Not Available]. PMID- 27549003 TI - [Not Available]. PMID- 27549004 TI - [Morbus Bowen under forste fingers negl]. PMID- 27549005 TI - [Methaemoglobinaemia induced by ingestion of alkyl nitrite, "poppers"]. AB - We present a case report of an 18-year-old male who was referred to the emergency department with evidence of methaemoglobinaemia. He presented with classic symptoms with peripheral cyanosis and hypoxia. Arterial blood gas showed a methaemoglobin level of 36%. This was caused by ingestion of alkyl nitrate, a widespread party drug called "poppers". When inhaled it causes euphoria, reduced pain and relaxation of the anal sphincter, but oral use may induce life threatening methaemoglobinaemia. The treatment of choice is the antidote methylene blue. After treatment the patient regained full recovery and was discharged on the following day. We discuss classic symptoms, diagnosis and treatment of intoxication with methylene blue. PMID- 27549006 TI - [Acute dyspnoea triggered by spontaneous pneumothorax in a pregnant woman with pulmonary agenesis]. AB - A 29-year-old pregnant woman was admitted to hospital with chest pain and dyspnoea. A thoracal computed tomography (CT) was performed to rule out pulmonary embolism, and it revealed a left-sided pneumothorax, which was treated with tube thoracostomy. Three days after discharge she was readmitted with spontaneous pressure pneumothorax. Her clinical condition did not improve, and a pulmonary scintigraphy and a new thoracal CT showed unilateral right pulmonary agenesis. Pulmonary agenesis is very rare in adulthood, and in this case it was complicated with spontaneous pneumothorax. PMID- 27549007 TI - [Neuralgic amyotrophy is an overlooked diagnosis by sudden onset of shoulder pain]. AB - Neuralgic amyotrophy (NA) is characterized by sudden onset of severe pain in the shoulder/upper arm and muscle amyotrophy. Up to 60% of patients with NA are misdiagnosed as having shoulder joint pathology or cervical pathology. We report a case of a 13-year-old girl diagnosed with the hereditary form of NA (HNA). Array comparative genomic hybridization showed a maternally inherited duplication of 1.5 Mb including the entire SEPT9-gene. The girl was treated with non steroidal anti-inflammatory drugs, corticosteroids and physiotherapy. Individuals with HNA should avoid extreme muscle activity and severe cold, as this may trigger attacks. PMID- 27549008 TI - A closure relation to molecular theory of solvation for macromolecules. AB - We propose a closure to the integral equations of molecular theory of solvation, particularly suitable for polar and charged macromolecules in electrolyte solution. This includes such systems as oligomeric polyelectrolytes at a finite concentration in aqueous and various non-aqueous solutions, as well as drug-like compounds in solution. The new closure by Kobryn, Gusarov, and Kovalenko (KGK closure) imposes the mean spherical approximation (MSA) almost everywhere in the solvation shell but levels out the density distribution function to zero (with the continuity at joint boundaries) inside the repulsive core and in the spatial regions of strong density depletion emerging due to molecular associative interactions. Similarly to MSA, the KGK closure reduces the problem to a linear equation for the direct correlation function which is predefined analytically on most of the solvation shells and has to be determined numerically on a relatively small (three-dimensional) domain of strong depletion, typically within the repulsive core. The KGK closure leads to the solvation free energy in the form of the Gaussian fluctuation (GF) functional. We first test the performance of the KGK closure coupled to the reference interaction site model (RISM) integral equations on the examples of Lennard-Jones liquids, polar and nonpolar molecular solvents, including water, and aqueous solutions of simple ions. The solvation structure, solvation chemical potential, and compressibility obtained from RISM with the KGK closure favorably compare to the results of the hypernetted chain (HNC) and Kovalenko-Hirata (KH) closures, including their combination with the GF solvation free energy. We then use the KGK closure coupled to RISM to obtain the solvation structure and thermodynamics of oligomeric polyelectrolytes and drug like compounds at a finite concentration in electrolyte solution, for which no convergence is obtained with other closures. For comparison, we calculate their solvation structure from molecular dynamics (MD) simulations. We further couple the 3D-RISM integral equation with the 3D-version of the KGK closure, and solve it for molecular mixtures as well as oligomeric polyelectrolytes and drug-like molecules in electrolyte solutions. PMID- 27549009 TI - Medical improvisation training to enhance the antenatal counseling skills of neonatologists and neonatal fellows: a pilot study. AB - INTRODUCTION: Neonatologists must be skilled at providing antenatal counseling to expectant parents of premature infants at the limits of viability. We conducted a medical improvisation workshop with the objective of enhancing antenatal counseling skills. METHODS: Pre- and postworkshop questionnaires were collected to examine the impact of the training. A follow-up survey was distributed 3 months after the workshop to examine the impact of the training on antenatal counseling skills. RESULTS: Nine neonatologists and three neonatal fellows participated in the workshop. Participants reported the skills learned in the workshop could enhance the quality of antenatal counseling. On follow-up survey, 90% of subjects reported improvements in the quality of their antenatal counseling. DISCUSSION: Participation in a medical improvisation workshop resulted in enhancements of self-perceived antenatal counseling skills. Medical improvisation training may provide a feasible and effective method of communication training for neonatologists. Further research into this innovative method are needed. PMID- 27549011 TI - Clinical findings in a patient with FARS2 mutations and early-infantile encephalopathy with epilepsy. AB - The FARS2 gene encodes the mitochondrial phenylalanyl-tRNA synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14, a clinical condition characterized by infantile onset epilepsy and encephalopathy. Mutations in FARS2 have been reported in only few patients, but a detailed description of seizures, electroencephalographic patterns, magnetic resonance imaging findings, and long-term follow-up is still needed. We provide a clinical report of a child with FARS2-related disease manifesting drug-resistant infantile spasms associated with focal seizures. By comparative genomic hybridization analysis we identified a heterozygous microdeletion in the short arm of chromosome 6, inherited from the mother, that encompasses the first coding exon of FARS2. By sequencing of the FARS2 gene we identified a variant c.1156C>G; p.(R386G), inherited from the father. By using standard spectrophotometric techniques in skin fibroblasts, we found a combined abnormality of complexes I and IV of the mitochondrial respiratory chain. The main clinical features of the patient included axial hypotonia, mild distal hypertonia, and psychomotor delay. The magnetic resonance imaging showed microcephaly, frontal cerebral atrophy, and signal changes of dentate nuclei. At the age of 3 years and 6 months, the patient was still under treatment with vigabatrin and he has been seizure free for the last 23 months. (c) 2016 Wiley Periodicals, Inc. PMID- 27549012 TI - Spontaneous separation of large-spin Fermi gas in the harmonic trap: a density functional study. AB - The component separation of the trapped large-spin Fermi gas is studied within density functional theory. The ground state and ferromagnetic transition in the gas, with and without the spin mixing collision, are calculated. In the absence of spin mixing, two patterns of separation are observed as the interaction between atoms increases, whereas only one of them corresponds to a ferromagnetic transition. The phase diagram suggests that the pattern which the system chooses depends on the interaction strength in the collision channels. With the presence of spin mixing, the distribution of phase region changes because of the interplay between different collision channels. Specifically, the spin exchange benefits the FM transition, while it suppresses the component separation of CS-II pattern. PMID- 27549013 TI - Real-World Assessment of Acute Left Ventricular Lead Implant Success and Complication Rates: Results from the Attain Success Clinical Trial. AB - BACKGROUND: Left ventricular lead (LVL) implant success rates have historically ranged between 70.5% and 95.5%. To date, there are few large studies that evaluate LVL implant success utilizing a single family of delivery catheters and leads. The Attain Success study was a prospective nonrandomized multicenter global study with the main objectives of assessing single-system LVL implant success and complication rates. METHODS: Patients undergoing cardiac resynchronization therapy implantation were eligible for enrollment. There was no prespecified level of experience for investigator participation. LVL implant success and complication rates were assessed though 3 months of follow-up. RESULTS: A total of 2,014 patients (69.1 +/- 12.0 years, 71% male and 38% atrial fibrillation) were enrolled from 114 centers with a follow-up of 3.5 +/- 2.1 months. Coronary sinus cannulation success rate was 96.4% with Attain Family delivery catheters. Implant success rate for Attain Family leads using Attain Family catheters was 94.0%; overall LVL implant success rate was 97.1%. Median procedure time was 4 minutes for cannulation and 9 minutes for LVL placement. Median fluoroscopy time was 17 minutes and median contrast used was 25 cc. There were 55 catheter or LVL-related complications in 53 subjects; the majority were LVL dislodgements (34, 1.7%) and extracardiac stimulation (11, 0.5%). The Kaplan Meier estimate of the 3-month complication probability was 2.6%. CONCLUSION: This study represents the largest prospective evaluation of LVL implantation to date, revealing a high LVL implant success rate and low complication rate using a single family of leads and delivery catheters. PMID- 27549014 TI - Editorial Comment to Postoperative infectious complications in patients undergoing holmium laser enucleation of the prostate: Risk factors and microbiological analysis. PMID- 27549015 TI - Improving Care Transitions Management: Examining the Role of Accountable Care Organization Participation and Expanded Electronic Health Record Functionality. AB - OBJECTIVE: Examine the extent to which physician organization participation in an accountable care organization (ACO) and electronic health record (EHR) functionality are associated with greater adoption of care transition management (CTM) processes. DATA SOURCES/STUDY SETTING: A total of 1,398 physician organizations from the third National Study of Physician Organization survey (NSPO3), a nationally representative sample of medical practices in the United States (January 2012-May 2013). STUDY DESIGN: We used data from the third National Study of Physician Organization survey (NSPO3) to assess medical practice characteristics, including CTM processes, ACO participation, EHR functionality, practice type, organization size, ownership, public reporting, and pay-for-performance participation. DATA COLLECTION/EXTRACTION METHODS: Multivariate linear regression models estimated the extent to which ACO participation and EHR functionality were associated with greater CTM capabilities, controlling for practice size, ownership, public reporting, and pay for-performance participation. PRINCIPAL FINDINGS: Approximately half (52.4 percent) of medical practices had a formal program for managing care transitions in place. In adjusted analyses, ACO participation (p < .001) and EHR functionality (p < .001) were independently associated with greater use of CTM processes among medical practices. CONCLUSIONS: The growth of ACOs and similar provider risk-bearing arrangements across the country may improve the management of care transitions by physician organizations. PMID- 27549016 TI - Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis. AB - Propensity score methods are used to reduce the effects of observed confounding when using observational data to estimate the effects of treatments or exposures. A popular method of using the propensity score is inverse probability of treatment weighting (IPTW). When using this method, a weight is calculated for each subject that is equal to the inverse of the probability of receiving the treatment that was actually received. These weights are then incorporated into the analyses to minimize the effects of observed confounding. Previous research has found that these methods result in unbiased estimation when estimating the effect of treatment on survival outcomes. However, conventional methods of variance estimation were shown to result in biased estimates of standard error. In this study, we conducted an extensive set of Monte Carlo simulations to examine different methods of variance estimation when using a weighted Cox proportional hazards model to estimate the effect of treatment. We considered three variance estimation methods: (i) a naive model-based variance estimator; (ii) a robust sandwich-type variance estimator; and (iii) a bootstrap variance estimator. We considered estimation of both the average treatment effect and the average treatment effect in the treated. We found that the use of a bootstrap estimator resulted in approximately correct estimates of standard errors and confidence intervals with the correct coverage rates. The other estimators resulted in biased estimates of standard errors and confidence intervals with incorrect coverage rates. Our simulations were informed by a case study examining the effect of statin prescribing on mortality. (c) 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID- 27549018 TI - Using holistic interpretive synthesis to create practice-relevant guidance for person-centred fundamental care delivered by nurses. AB - Nursing policy and healthcare reform are focusing on two, interconnected areas: person-centred care and fundamental care. Each initiative emphasises a positive nurse-patient relationship. For these initiatives to work, nurses require guidance for how they can best develop and maintain relationships with their patients in practice. Although empirical evidence on the nurse-patient relationship is increasing, findings derived from this research are not readily or easily transferable to the complexities and diversities of nursing practice. This study describes a novel methodological approach, called holistic interpretive synthesis (HIS), for interpreting empirical research findings to create practice-relevant recommendations for nurses. Using HIS, umbrella review findings on the nurse-patient relationship are interpreted through the lens of the Fundamentals of Care Framework. The recommendations for the nurse-patient relationship created through this approach can be used by nurses to establish, maintain and evaluate therapeutic relationships with patients to deliver person centred fundamental care. Future research should evaluate the validity and impact of these recommendations and test the feasibility of using HIS for other areas of nursing practice and further refine the approach. PMID- 27549019 TI - Discovery of Fe-Ce Oxide/BiVO4 Photoanodes through Combinatorial Exploration of Ni-Fe-Co-Ce Oxide Coatings. AB - An efficient photoanode is a prerequisite for a viable solar fuels technology. The challenges to realizing an efficient photoanode include the integration of a semiconductor light absorber and a metal oxide electrocatalyst to optimize corrosion protection, light trapping, hole transport, and photocarrier recombination sites. To efficiently explore metal oxide coatings, we employ a high-throughput methodology wherein a uniform BiVO4 film is coated with 858 unique metal oxide coatings covering a range of metal oxide loadings and the full (Ni-Fe-Co-Ce)Ox pseudoquaternary composition space. Photoelectrochemical characterization of the photoanodes reveals that specific combinations of metal oxide composition and loading provide up to a 13-fold increase in the maximum photoelectrochemical power generation for oxygen evolution in pH 13 electrolyte. Through mining of the high-throughput data we identify composition regions that form improved interfaces with BiVO4. Of particular note, integrated photoanodes with catalyst compositions in the range Fe(0.4-0.6)Ce(0.6-0.4)Ox exhibit high interface quality and excellent photoelectrochemical power conversion. Scaled-up inkjet-printed electrodes and photoanodic electrodeposition of this composition on BiVO4 confirms the discovery and the synthesis-independent interface improvement of (Fe-Ce)Ox coatings on BiVO4. PMID- 27549017 TI - Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses. AB - Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge. PMID- 27549020 TI - Improving access to medicines for non-communicable diseases in rural India: a mixed methods study protocol using quasi-experimental design. AB - BACKGROUND: India has the distinction of financing its healthcare mainly through out-of-pocket expenses by individual families contributing to catastrophic health expenditure and impoverishment. Nearly 70 % of the expenditure is on medicines purchased at private pharmacies. Patients with chronic ailments are especially affected, as they often need lifelong medicines. Over the past years in India, there have been several efforts to improve drug availability at government primary health centres. In this study, we aim to understand health system factors that affect utilisation and access to generic medicines for people with non communicable diseases. METHODS: This study aims to understand if (and how) a package of interventions targeting primary health centres and community participation platforms affect utilisation and access to generic medicines for people with non-communicable diseases in the current district context in India. This study will employ a quasi-experimental design and a qualitative theory driven approach. PHCs will be randomly assigned to one of three arms of the intervention. In one arm, PHCs will receive inputs to optimise service delivery for non-communicable diseases, while the second arm will receive an additional package of interventions to strengthen community participation platforms for improving non-communicable disease care. The third arm will be the control. We will conduct household and facility surveys, before and after the intervention and will estimate the effect of the intervention by difference-in-difference analysis. Sample size for measuring effects was calculated based on obtaining at least 30 households for each primary health centre spread across three distance based clusters. Primary outcomes include availability and utilisation of medicines at primary health centres and out-of-pocket expenditure for medicines by non-communicable disease households. Focus group discussions with patients and in-depth interviews with health workers will also be conducted. Qualitative and process documentation data will be used to explain how the intervention could have worked. DISCUSSION: By taking into consideration several health system building blocks and trying to understand how they interact, our study aims to generate evidence for health planners on how to optimise health services to improve access to medicines. TRIAL REGISTRATION: Protocol registered on Clinical Trials Registry of India with registration identifier number CTRI/2015/03/005640 on 17(th) March 2015. PMID- 27549021 TI - C-H Bond Activation/Arylation Catalyzed by Arene-Ruthenium-Aniline Complexes in Water. AB - Water-soluble arene-ruthenium complexes coordinated with readily available aniline-based ligands were successfully employed as highly active catalysts in the C-H bond activation and arylation of 2-phenylpyridine with aryl halides in water. A variety of (hetero)aryl halides were also used for the ortho-C-H bond arylation of 2-phenylpyridine to afford the corresponding ortho- monoarylated products as major products in moderate to good yields. Our investigations, including time-scaled NMR spectroscopy and mass spectrometry studies, evidenced that the coordinating aniline-based ligands, having varying electronic and steric properties, had a significant influence on the catalytic activity of the resulting arene-ruthenium-aniline-based complexes. Moreover, mass spectrometry identification of the cycloruthenated species, {(eta6 -arene)Ru(kappa2 -C,N phenylpyridine)}+ , and several ligand-coordinated cycloruthenated species, such as [(eta6 -arene)Ru(4-methylaniline)(kappa2 -C,N-phenylpyridine)]+ , found during the reaction of 2-phenylpyridine with the arene-ruthenium-aniline complexes further authenticated the crucial roles of these species in the observed highly active and tuned catalyst. At last, the structures of a few of the active catalysts were also confirmed by single-crystal X-ray diffraction studies. PMID- 27549022 TI - Fear of Negative Evaluation Moderates the Effect of Subliminal Fear Priming on Rejection of Unfair Offers in the Ultimatum Game. AB - The purpose of this study was to examine whether the tendency to fear negative evaluation moderates the effect of fear emotion on the rejection of unfair offers in the ultimatum game (UG). A photograph of a fearful face or landscape was displayed subliminally (i.e., for 10 ms) before the proposer's offer in the UG was presented to participants. We used the Fear of Negative Evaluation Scale (FNES) to measure participants' anxiety regarding negative evaluations from others. Results showed a significant interaction between FNES and condition (fearful face vs. landscape) in relation to the rejection of an unfair offer. Furthermore, the mean rejection rate of an unfair offer was significantly higher in the fearful face condition relative to that in the landscape condition among participants whose FNES scores were higher than the median; however, this difference was not observed in participants whose FNES scores were lower than the median. These results suggest that fear of negative evaluation moderates the effect of subliminal fear priming on the rejection of unfair offers in the UG, and that negative emotion induced by unconscious stimuli enhances rejection of these unfair offers. PMID- 27549023 TI - Does poor ovarian response to gonadotrophins predict early menopause? A retrospective cohort study with minimum of 10-year follow-up. AB - One in 10 women reach menopause before they are 45 years of age, and 1 in 100 before 40. In most cases, poor ovarian response to gonadotrophins is a result of poor ovarian reserve. An early menopause is associated with long-term health risks. Identifying women at risk may allow appropriate measures to be instigated early. Women aged <40 years treated in the Aberdeen Fertility Centre between 1998 and 2002 were identified. Those with poor response to an age appropriate dose of gonadotrophins (obtaining <=3 eggs or had cycle cancelled) after exclusion of hypothalamic insufficiency, or whose cycle was cancelled due to poor response were age matched with good responders (6-15 eggs). In this retrospective cohort study, women who have had IVF at least 10 years ago (157 poor responders and 314 good responders) were sent a postal questionnaire to determine age at menopause. A total of 219 women (64 poor responders, 155 good responders) returned their questionnaires. Poor responders were more likely to have premature menopause (3% vs. 0%; p = .024). A higher proportion of poor responders experienced early menopause (11% vs. 3%; p = .044). Despite being the first study with a 10-year follow-up, this study is limited to one centre and has a small number of women reaching premature menopause. Poor response to gonadotrophins in the context of IVF treatment is a marker of reduced ovarian reserve and is associated with early menopause. Results of this study underline the need for larger studies with long term follow-up. PMID- 27549024 TI - Spinal epidural haematoma following thrombolysis for acute ischaemic stroke in patient within 48h of emergency lumbar microdiscectomy. AB - The ideal regimen and the optimal starting point for thromboembolic prophylaxis in spinal procedures remain unclear. We report a case of postoperative spinal epidural haematoma following thrombolysis for stroke in patient within 48 h of emergency lumbar microdiscectomy. Thrombolysis should be considered in patients with spinal surgery who developed arterial cerebral thrombosis. PMID- 27549025 TI - Enhanced angiogenesis, hypoxia and neutrophil recruitment during Myc-induced liver tumorigenesis in zebrafish. AB - Angiogenesis, hypoxia and immune cells are important components in tumor microenvironment affecting tumor growth. Here we employed a zebrafish liver tumor model to investigate the effect of Myc expression on angiogenesis, hypoxia and tumor-infiltrated neutrophils during the tumor initiation stage. We found that induced Myc expression in the liver caused a dramatic increase of liver size with neoplastic features. The tumorigenic liver was accompanied by enhanced angiogenesis and inhibition of angiogenesis by an inhibitor (SU5416 or sunitinib) hindered the tumorigenic growth, suggesting an essential role of angiogenesis in tumorigenic growth of liver tumor in this zebrafish model. Myc induction also caused hypoxia, which could be further enhanced by hypoxia activator, ML228, to lead to a further enlargement of tumorigenic liver. Furthermore, Myc overexpression incurred an increase of liver-infiltrated neutrophils and the increase could be suppressed by angiogenesis inhibitors or by morpholino knockdown inhibition of neutrophil differentiation, leading to a suppression of growth of tumorigenic livers. Finally, the enhanced angiogenesis, hypoxia and tumor-infiltrated neutrophils by Myc overexpression were validated by RT-qPCR examination of expression of relevant biomarker genes. In sum, the current study demonstrated that the Myc-induced liver tumor model in zebrafish provides an excellent platform for study of tumor microenvironment. PMID- 27549027 TI - Nano electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA) of liposomes: applicability of the technique for nano vesicle batch control. AB - Liposomes are biodegradable nanoparticle vesicles consisting of a lipid bilayer encapsulating an aqueous core. Entrapped cargo material is shielded from the extra-vesicular medium and sustained release of encapsulated material can be achieved. However, application of liposomes as nano-carriers demands their characterization concerning size and size distribution, particle-number concentration, occurrence of vesicle building blocks in solution and determination of the resulting vesicle encapsulation capacity. These questions can be targeted via gas-phase electrophoretic mobility molecular analysis (GEMMA) based on a nano electrospray (nES) charge-reduction source. This instrument separates single-charged nanoparticles in the gas-phase according to size in a high-laminar sheath-flow by means of an orthogonal, tunable electric field. nES GEMMA analysis enables to confirm liposome integrity after passage through the instrument (in combination with atomic force microscopy) as well as to exclude vesicle aggregation. Additionally, nanoparticle diameters at peak apexes and size distribution data are obtained. Differences of hydrodynamic and dry particle diameter values, as well as the effect of number- and mass-based concentration data analysis on obtained liposome diameters are shown. Furthermore, the repeatability of liposome preparation is studied, especially upon incorporation of PEGylated lipids in the bilayer. Finally, the instruments applicability to monitor mechanical stress applied to vesicles is demonstrated. PMID- 27549028 TI - Technology Based Treatment for UreteroPelvic Junction Obstruction. AB - Surgical management of ureteropelvic junction obstruction (UPJO) has historically been performed with open pyeloplasty. With the advent of endourology, laparoscopy, and robotics, minimally-invasive techniques have been described and accepted as alternatives to open surgery. Each of these approaches has its own advantages and disadvantages, equipment needs, degree of invasiveness, and experience of the treating urologist. Advocates and critics have their own say as to their preferred technique. In this article, we review the chronological evolution of these techniques and discuss their current role in the management of UPJO. PMID- 27549026 TI - The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases. AB - Rheumatoid arthritis affects nearly 1% of the world's population and is a debilitating autoimmune condition that can result in joint destruction. During the past decade, inflammatory functions have been described for signalling molecules classically involved in apoptotic and non-apoptotic death pathways, including, but not limited to, Toll-like receptor signalling, inflammasome activation, cytokine production, macrophage polarization and antigen citrullination. In light of these remarkable advances in the understanding of inflammatory mechanisms of the death machinery, this Review provides a snapshot of the available evidence implicating death pathways, especially within the phagocyte populations of the innate immune system, in the perpetuation of rheumatoid arthritis and other rheumatic diseases. Elevated levels of signalling mediators of both extrinsic and intrinsic apoptosis, as well as the autophagy, are observed in the joints of patients with rheumatoid arthritis. Furthermore, risk polymorphisms are present in signalling molecules of the extrinsic apoptotic and autophagy death pathways. Although research into the mechanisms underlying these pathways has made considerable progress, this Review highlights areas where further investigation is particularly needed. This exploration is critical, as new discoveries in this field could lead to the development of novel therapies for rheumatoid arthritis and other rheumatic diseases. PMID- 27549029 TI - Racial and Ethnic Differences in Initiation and Discontinuation of Antidementia Drugs by Medicare Beneficiaries. AB - OBJECTIVES: To examine racial and ethnic differences in initiation and time to discontinuation of antidementia medication in Medicare beneficiaries. DESIGN: Retrospective cohort study. SETTING: Secondary analysis of 2009-10 enrollment, claims, and Part D prescription data for a 10% national sample of U.S. Medicare fee-for-service beneficiaries. PARTICIPANTS: Beneficiaries aged 65 and older with Alzheimer's disease or related dementia (ADRD) before 2009 and no fills for antidementia medications in the first half of 2009 (N = 84,043). MEASUREMENTS: Initiation was defined as having one or more fills for antidementia medication in the second half of 2009 and discontinuation as a gap in coverage of 30 days or more during the year after initiation. The Andersen Behavioral Model was used to guide covariate selection. RESULTS: Overall, 3,481 (4.1%) of previous nonusers initiated antidementia medication in the second half of 2009. Of those initiating one drug class (acetylcholinesterase inhibitors (AChEIs) or memantine), 9% later added the other class, and 2% switched classes. Of initiators, 23% discontinued within 1 month, and 62% discontinued within 1 year. Hispanic beneficiaries were more likely than white beneficiaries to initiate (adjusted odds ratio = 1.25, 95% confidence interval (CI) = 1.10-1.41). Black and white beneficiaries did not differ in likelihood of initiation. Hispanic (adjusted hazard ratio (aHR) = 1.56, 95% CI = 1.34-1.82) and black (aHR = 1.25, 95% CI = 1.08-1.44) beneficiaries discontinued at a faster rate than white beneficiaries. CONCLUSION: Initiation of antidementia medications was no different in black and white beneficiaries and more likely in Hispanic beneficiaries; black and Hispanic beneficiaries discontinued at a faster rate. More research into reasons explaining these differences is needed. PMID- 27549030 TI - Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential. AB - A species that requires sexual reproduction but cannot reproduce is doomed to extinction. The important increasing loss of species emphasizes the ecological significance of elucidating the effects of environmental stressors, such as pesticides, on reproduction. Despite its special reproductive behavior, the honey bee was selected as a relevant and integrative environmental model because of its constant and diverse exposure to many stressors due to foraging activity. The widely used insecticide Fipronil, the use of which is controversial because of its adverse effects on honey bees, was chosen to expose captive drones in hives via syrup contaminated at 0.1 MUg/L and gathered by foragers. Such environmental exposure led to decreased spermatozoa concentration and sperm viability coupled with an increased sperm metabolic rate, resulting in drone fertility impairment. Subsequently, unexposed queens inseminated with such sperm exhibited fewer spermatozoa with lower viability in their spermatheca, leaving no doubt about the detrimental consequences for the reproductive potential of queens, which are key for colony sustainability. These findings suggest that pesticides could contribute to declining honey bee populations through fertility impairment, as exemplified by Fipronil. More broadly, reproductive disorders should be taken into consideration when investigating the decline of other species. PMID- 27549032 TI - Dietary advice on prescription: experiences with a weight reduction programme. AB - AIMS AND OBJECTIVES: To describe overweight persons' experiences with weight reduction and participation in the dietary advice on prescription. BACKGROUND: Approximately 20% of overweight individuals are able to successfully lose weight. Experiences from earlier weight reduction programmes indicate that those who succeed typically manage to avoid overeating to handle stress and have high motivation to lose weight. Those who fail have low self-control and engage in negative health behaviours such as eating when experiencing negative emotions and stress. DESIGN: The study used a descriptive qualitative design and was conducted at a Primary Health Care Centre in south-west Sweden. METHODS: The first nineteen study participants who completed the weight reduction programme in two years responded in writing to five open questions about their experiences with the programme. Data were analysed using inductive content analysis. RESULTS: The participants appreciated the face-to-face meetings with the nurse because they felt seen and listened to during these sessions. They also felt their life situations and self-discipline had an impact on how well they were able to follow the programme. Dietary advice on prescription advice was considered to be helpful for achieving behavioural changes and losing weight. People who succeeded in sustainably losing weight described the importance of support from partners or close friends. CONCLUSIONS: To achieve sustainable weight reduction, it is important to individualise the programme in order to address each person's life situation and the unique difficulties they may encounter. RELEVANCE TO CLINICAL PRACTICE: Motivational interviewing appears to be a good technique for developing a successful relationship between the nurse and the patient. The dietary advice on prescription advice was perceived to be a good way to improve food habits and can easily be used at many Primary Health Care Centres. Patient's partners should also be offered the opportunity to participate in the programme. PMID- 27549031 TI - Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-1. AB - Skeletal muscle atrophy, referred to as sarcopenia, is often observed in chronic kidney disease (CKD) patients, especially in patients who are undergoing hemodialysis. The purpose of this study was to determine whether uremic toxins are involved in CKD-related skeletal muscle atrophy. Among six protein-bound uremic toxins, indole containing compounds, indoxyl sulfate (IS) significantly inhibited proliferation and myotube formation in C2C12 myoblast cells. IS increased the factors related to skeletal muscle breakdown, such as reactive oxygen species (ROS) and inflammatory cytokines (TNF-alpha, IL-6 and TGF-beta1) in C2C12 cells. IS also enhanced the production of muscle atrophy-related genes, myostatin and atrogin-1. These effects induced by IS were suppressed in the presence of an antioxidant or inhibitors of the organic anion transporter and aryl hydrocarbon receptor. The administered IS was distributed to skeletal muscle and induced superoxide production in half-nephrectomized (1/2 Nx) mice. The chronic administration of IS significantly reduced the body weights accompanied by skeletal muscle weight loss. Similar to the in vitro data, IS induced the expression of myostatin and atrogin-1 in addition to increasing the production of inflammatory cytokines by enhancing oxidative stress in skeletal muscle. These data suggest that IS has the potential to accelerate skeletal muscle atrophy by inducing oxidative stress-mediated myostatin and atrogin-1 expression. PMID- 27549033 TI - High time-resolved elemental components in fine and coarse particles in the Pearl River Delta region of Southern China: Dynamic variations and effects of meteorology. AB - Hourly-resolved PM2.5 and PM10-2.5 samples were collected in the industrial city Foshan in the Pearl River Delta region, China. The samples were subsequently analyzed for elemental components and black carbon (BC). A key purpose of the study was to understand the composition of particulate matter (PM) at high-time resolution in a polluted urban atmosphere to identify key components contributing to extreme PM concentration events and examine the diurnal chemical concentration patterns for air quality management purposes. It was found that BC and S concentrations dominated in the fine mode, while elements with mostly crustal and oceanic origins such as Si, Ca, Al and Cl were found in the coarse size fraction. Most of the elements showed strong diurnal variations. S did not show clear diurnal variations, suggesting regional rather than local origin. Based on empirical orthogonal functions (EOF) method, 3 forcing factors were identified contributing to the extreme events of PM2.5 and selected elements, i.e., urban direct emissions, wet deposition and a combination of coarse mode sources. Conditional probability functions (CPF) were performed using wind profiles and elemental concentrations. The CPF results showed that BC and elemental Cl, K, Fe, Cu and Zn in the fine mode were mostly from the northwest, indicating that industrial emissions and combustion were the main sources. For elements in the coarse mode, Si, Al, K, Ca, Fe and Ti showed similar patterns, suggesting same sources such as local soil dust/construction activities. Coarse elemental Cl was mostly from the south and southeast, implying the influence of marine aerosol sources. For other trace elements, we found vanadium (V) in fine PM was mainly from the sources located to the southeast of the measuring site. Combined with CPF results of S and V in fine PM, we concluded shipping emissions were likely an important elemental emission source. PMID- 27549034 TI - Comparison of double-balloon and single-balloon enteroscope for therapeutic endoscopic retrograde cholangiography after Roux-en-Y small bowel surgery. AB - BACKGROUND: Roux-en-Y reconstructive surgery excludes the biliopancreatic system from conventional endoscopic access. Balloon-assisted enteroscopy allows therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in these patients, avoiding rescue surgery. The objective of the current study is to compare success and complication rate of double-balloon (DBE) and single-balloon enteroscope (SBE) to perform ERCP in Roux-en-Y patients. METHODS: Seventy three Roux-en-Y patients with suspected biliary tract pathology underwent balloon assisted enteroscopy in a tertiary-care center. Retrospective analysis of 95 consecutive therapeutic ERCP procedures was performed to define and compare success and complication rate of DBE and SBE. RESULTS: Male-female ratio was 28/45 with a mean age of 58 +/- 2 years. 30 (32 %) procedures were performed with DBE and 65 (68 %) with SBE. Overall ERCP success rate was 73 % for DBE and 75 % for SBE (P = 0.831). Failure was due to inability to reach or cannulate the intact papilla or bilioenteric anastomosis. Success rate was significantly higher when performed at the bilioenteric anastomosis (80 % success in 56 procedures) or at the intact papilla in short-limb Roux-en-Y (80 % in 15 procedures) as compared to the intact papilla in long-limb (58 % in 24 procedures; P = 0.040). Adverse event rates were 10 % (DBE) and 8 % (SBE) (P = 0.707) and mostly dealt with conservatively. CONCLUSIONS: ERCP after Roux-en-Y altered small bowel anatomy is feasible and safe using both DBE and SBE. Both techniques are equally competent with high success rates and acceptable adverse events rates. ERCP at the level of the intact papilla in long limb Roux-en-Y is less successful as compared to short limb or bilioenteric anastomosis. PMID- 27549035 TI - The infralimbic and prelimbic cortices contribute to the inhibitory control of cocaine-seeking behavior during a discriminative stimulus task in rats. AB - The infralimbic and prelimbic (IL and PL, respectively) regions of the medial prefrontal cortex regulate the control of drug-seeking behavior. However, their roles in cocaine seeking in a discriminative stimulus (DS)-based self administration task are unclear. To address this issue, male Sprague Dawley rats were trained on a DS task in which, on a trial-by-trial basis, a DS+ indicated that a lever press would produce a cocaine infusion, whereas a distinct DS- indicated that a lever press would produce nothing. IL and PL inactivation via GABA receptor activation decreased performance accuracy and disinhibited behavioral responding on DS- trials, resulting in greater lever pressing during the DS- presentation. This was accompanied by a decrease in cocaine infusions obtained, a finding confirmed in a subsequent experiment using a standard FR1 cocaine self-administration paradigm. We repeated the DS study using a food reward and found that inactivation of each region decreased performance accuracy but had no effect on the total number of food pellets earned. Additional experiments with the cocaine DS task found that dopamine receptor blockade in the IL, but not PL, reduced performance accuracy and disinhibited behavioral responding on DS- trials, whereas AMPA receptor blockade in the IL and PL had no effect on performance accuracy. These findings strongly suggest that, in a DS based self-administration task in which rats must actively decide whether to engage in lever pressing (DS+) or withhold lever pressing (DS-) on a trial-by trial basis, both the IL and PL contribute to the inhibitory control of drug seeking behavior. PMID- 27549073 TI - Associations Between Serum Inflammatory Markers and Hippocampal Volume in a Community Sample. AB - OBJECTIVES: To quantify associations between inflammatory biomarkers and hippocampal volume (HV) and to examine effect modification according to sex, race, and age. DESIGN: Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized beta-coefficients adjusted for age, sex, race, and education. SETTING: Community cohorts in Jackson, Mississippi and Rochester, Minnesota. PARTICIPANTS: The Genetic Epidemiology Network of Arteriopathy study. MEASUREMENTS: C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors 1 (sTNFR 1) and 2 (sTNFR-2) from peripheral blood were measured in a sample of 773 non Hispanic whites (61% women, aged 60.2 +/- 9.8) and 514 African Americans (70% women, aged 63.9 +/- 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. RESULTS: In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation (SD) increase in sTNFR-1 was associated with 59.1 mm(3) (95% confidence interval (CI) = -101.4 to -16.7 mm(3) ) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm(3) (95% CI = -92.2 to -5.3 mm(3) ) smaller HV. Relationships were stronger for sTNFR-2 in men (HV = -116.6 mm(3) for each SD increase, 95% CI = -201.0 to -32.1) than women (HV = -26.0 per SD increase, 95% CI = -72.4-20.5) and sTNFR-1 in non-Hispanic whites (HV = -84.7 mm(3) per SD increase, 95% CI = -142.2 to -27.1) than African Americans (HV = 14.1 mm(3) per SD increase, 95% CI = -78.3-50.1). Associations between IL-6 or CRP and HV were not supported. CONCLUSION: Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late life cognitive impairment. PMID- 27549074 TI - An Evaluation and Ranking of Children's Hospital Websites in the United States. AB - BACKGROUND: Children's hospitals are faced with the rising need for technological innovation. Their prospective health care consumers, who increasingly depend on the Web and social media for communication and consumer engagement, drive this need. As patients and family members navigate the Web presence of hospitals, it is important for these specialized organizations to present themselves and their services efficiently. OBJECTIVE: The purpose of this study was to evaluate the website content of children's hospitals in order to identify opportunities to improve website design and create benchmarks to judge improvement. METHODS: All websites associated with a children's hospital were identified using a census list of all children's hospitals in the United States. In March of 2014, each website and its social media were evaluated using a Web crawler that provided a 5 dimensional assessment that included website accessibility, marketing, content, technology, and usability. The 5-dimensional assessment was scored on a scale ranging from 0 to 10 with positive findings rated higher on the scale. Websites were ranked by individual dimensions as well as according to their average ranking across all dimensions. RESULTS: Mean scores of 153 websites ranged from 5.05 to 8.23 across all 5 dimensions. Results revealed that no website scored a perfect 10 on any dimension and that room exists for meaningful improvement. CONCLUSIONS: Study findings allow for the establishment of baseline benchmarks for tracking future website and social media improvements and display the need for enhanced Web-based consumer engagement for children's hospitals. PMID- 27549075 TI - A new phase modulated binomial-like selective-inversion sequence for solvent signal suppression in NMR. AB - A new 8-pulse Phase Modulated binomial-like selective inversion pulse sequence, dubbed '8PM', was developed by optimizing the nutation and phase angles of the constituent radio-frequency pulses so that the inversion profile resembled a target profile. Suppression profiles were obtained for both the 8PM and W5 based excitation sculpting sequences with equal inter-pulse delays. Significant distortions were observed in both profiles because of the offset effect of the radio frequency pulses. These distortions were successfully reduced by adjusting the inter-pulse delays. With adjusted inter-pulse delays, the 8PM and W5 based excitation sculpting sequences were tested on an aqueous lysozyme solution. The 8 PM based sequence provided higher suppression selectivity than the W5 based sequence. Two-dimensional nuclear Overhauser effect spectroscopy experiments were also performed on the lysozyme sample with 8PM and W5 based water signal suppression. The 8PM based suppression provided a spectrum with significantly increased (~ doubled) cross-peak intensity around the suppressed water resonance compared to the W5 based suppression. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27549076 TI - Computerized test versus personal interview as admission methods for graduate nursing studies: A retrospective cohort study. AB - The purpose of this study was to compare the predictive validity, economic efficiency, and faculty staff satisfaction of a computerized test versus a personal interview as admission methods for graduate nursing studies. A mixed method study was designed, including cross-sectional and retrospective cohorts, interviews, and cost analysis. One hundred and thirty-four students in the Master of Nursing program participated. The success of students in required core courses was similar in both admission method groups. The personal interview method was found to be a significant predictor of success, with cognitive variables the only significant contributors to the model. Higher satisfaction levels were reported with the computerized test compared with the personal interview method. The cost of the personal interview method, in annual hourly work, was 2.28 times higher than the computerized test. These findings may promote discussion regarding the cost benefit of the personal interview as an admission method for advanced academic studies in healthcare professions. PMID- 27549077 TI - Gastric carcinoma in canines and humans, a review. AB - Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC. PMID- 27549078 TI - Correction: Chiral sensing of amino acids and proteins chelating with Eu(III) complexes by Raman optical activity spectroscopy. AB - Correction for 'Chiral sensing of amino acids and proteins chelating with Eu(III) complexes by Raman optical activity spectroscopy' by Tao Wu et al., Phys. Chem. Chem. Phys., 2016, DOI: 10.1039/c6cp03968e. PMID- 27549079 TI - Diagnostic performance of molecular and conventional methods for identification of dermatophyte species from clinically infected Arabian horses in Egypt. AB - BACKGROUND: Rapid and accurate identification of dermatophytes is crucial for the effective control of disease outbreaks. Current methods based on culture and microscopic characteristics may require weeks before positive identification is made. OBJECTIVES: To (i) identify the most common pathogenic dermatophytes affecting Arabian horses; (ii) compare the performance of direct microscopy (DM), culture, PCR using hair samples (PCRhair ) and PCR based on culture isolates (PCRculture ) for the diagnosis of dermatophytosis. METHODS: Samples of hair and crusts of skin lesions from Arabian horses were collected on a monthly basis by scraping skin of affected horses. Samples were divided into three portions: the first portion was used for microscopic examination, the second for culture and the third portion for PCR amplification of intergenic spacer (ITS) regions. RESULTS: Out of 200 horses examined, 70 (35%) showed cutaneous lesions characteristic of dermatophytosis. DM revealed that 70.4% were positive for fungal elements and 85.7% were culture positive. The identified species were Microsporum canis, Trichophyton verrucosum, T. mentagrophytes var. mentagrophytes and M. equinum. Among 25 selected samples, 64, 92, 91.3 and 52% were positive for dermatophytes, as determined by DM, culture, PCRculture and PCRhair , respectively. CONCLUSIONS: The dermatophytes M. canis, T. verrucosum, T. mentagrophytes var. mentagrophytes and M. equinum were the most common cause of dermatophytosis in Arabian horses. Although the number of samples was small, the ITS-based PCR may be a useful diagnostic tool when combined with culture. PMID- 27549080 TI - Computational quality control tools for mass spectrometry proteomics. AB - As mass-spectrometry-based proteomics has matured during the past decade, a growing emphasis has been placed on quality control. For this purpose, multiple computational quality control tools have been introduced. These tools generate a set of metrics that can be used to assess the quality of a mass spectrometry experiment. Here we review which types of quality control metrics can be generated, and how they can be used to monitor both intra- and inter-experiment performances. We discuss the principal computational tools for quality control and list their main characteristics and applicability. As most of these tools have specific use cases, it is not straightforward to compare their performances. For this survey, we used different sets of quality control metrics derived from information at various stages in a mass spectrometry process and evaluated their effectiveness at capturing qualitative information about an experiment using a supervised learning approach. Furthermore, we discuss currently available algorithmic solutions that enable the usage of these quality control metrics for decision-making. PMID- 27549082 TI - The effect of question order on evaluations of test performance: Can the bias dissolve? AB - Question difficulty order has been shown to affect students' global postdictions of test performance. We attempted to eliminate the bias by letting participants experience the question order manipulation multiple times. In all three experiments, participants answered general knowledge questions and self-evaluated their performance. In Experiment 1, participants studied questions and answers in easy-hard or hard-easy question order prior to taking a test in the same order. In Experiment 2, participants took the same test twice in the opposite question order (easy-hard then hard-easy, or hard-easy then easy-hard). In Experiment 3, participants took two different tests in the opposite question order (easy-hard then hard-easy, or hard-easy then easy-hard). In all three experiments, we were unable to eliminate the bias, which suggests that repeated exposure is insufficient to overcome a strong initial anchor. PMID- 27549081 TI - Novel cationic peptide TP359 down-regulates the expression of outer membrane biogenesis genes in Pseudomonas aeruginosa: a potential TP359 anti-microbial mechanism. AB - BACKGROUND: Antimicrobial peptides (AMPs) are a class of antimicrobial agents with broad-spectrum activities. Several reports indicate that cationic AMPs bind to the negatively charged bacterial membrane causing membrane depolarization and damage. However, membrane depolarization and damage may be insufficient to elicit cell death, thereby suggesting that other mechanism(s) of action could be involved in this phenomenon. In this study, we investigated the antimicrobial activity of a novel antimicrobial peptide, TP359, against two strains of Pseudomonas aeruginosa, as well as its possible mechanisms of action. RESULTS: TP359 proved to be bactericidal against P. aeruginosa as confirmed by the reduced bacteria counts, membrane damage and cytoplasmic membrane depolarization. In addition, it was non-toxic to mouse J774 macrophages and human lung A549 epithelial cells. Electron microscopy analysis showed TP359 bactericidal effects by structural changes of the bacteria from viable rod-shaped cells to those with cell membrane damages, proceeding into the efflux of cytoplasmic contents and emergence of ghost cells. Gene expression analysis on the effects of TP359 on outer membrane biogenesis genes underscored marked down-regulation, particularly of oprF, which encodes a major structural and outer membrane porin (OprF) in both strains studied, indicating that the peptide may cause deregulation of outer membrane genes and reduced structural stability which could lead to cell death. CONCLUSION: Our data shows that TP359 has potent antimicrobial activity against P aeruginosa. The correlation between membrane damage, depolarization and reduced expression of outer membrane biogenesis genes, particularly oprF may suggest the bactericidal mechanism of action of the TP359 peptide. PMID- 27549083 TI - Salivary and serum adiponectin and C-reactive protein levels in acute myocardial infarction related to body mass index and oral health. AB - BACKGROUND AND OBJECTIVE: Adiponectin is produced by adipose cells and is considered an anti-inflammatory molecule. In contrast, C-reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk. MATERIAL AND METHODS: This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be affected by both the body mass index and oral health characteristics of the individuals. RESULTS: Significantly lower adiponectin levels were observed in the serum of patients with AMI. Serum adiponectin in both groups and salivary adiponectin in patients with AMI decreased with increasing body mass index. Oral health was significantly worse in patients with AMI, and both serum and salivary adiponectin were elevated with better oral health in control subjects. Serum CRP levels were increased in patients with AMI regardless of their oral health, and both serum and salivary CRP were significantly elevated in S-T wave elevated patients with MI. CONCLUSIONS: These initial data provide evidence relating obesity and oral health to salivary and serum analyte levels that occur in association with cardiac events. Relationships have been described between CVD risk and periodontal disease. Additionally, various systemic inflammatory biomarkers appear to reflect both the CVD risk and the extent/severity of periodontitis. Our findings indicated that oral health and obesity contribute to altering levels of these salivary and serum analytes in association with cardiac events. The potential that serum and/or salivary biomarkers could aid in evaluating CVD risk requires knowledge regarding how the oral health of the individual would impact the effectiveness of these biological measures. PMID- 27549084 TI - Color radiography in lung nodule detection and characterization: comparison with conventional gray scale radiography. AB - BACKGROUND: To compare the capability of lung nodule detection and characterization between dual-energy radiography with color-representation (DCR) and conventional gray scale chest radiography (GSR). METHODS: A total of 130 paired chest radiographs (DCR and GSR) obtained from 65 patients (14 with normal scans and 51 with pulmonary nodules) were evaluated. After analysis, 45 non calcified and 21 calcified nodules were identified. DCR was obtained by adding color space within material-decomposed data (blue for high attenuation and red for low attenuation) and by compounding the manipulated data to one color image. Three radiologists marked suggested nodules on radiographic images and assessed the level of confidence of lesion presence and probability of nodule calcification by using a nine-point rating scale. The jackknife active free response receiver operating characteristics (JAFROC) analysis was used to evaluate lesion detectability, and multi-reader multi-case receiver operating characteristics (MRMC ROC) analysis was used for the evaluation of the accuracy of nodule calcification prediction. RESULTS: Figures of merit (FOM) from JAFROC was 0.807 for DCR and 0.811 for GSR, respectively; nodule detectability was not significantly different between DCR and GSR (p = 0.93). Areas under curve (AUC) from MRMC ROC were 0.944 for DCR and 0.828 for GSR, respectively; performance of DCR in predicting lung nodule calcification was significantly higher than that of GSR (p = 0.04). CONCLUSIONS: DCR showed similar performance in terms of lung nodule detection compared with GSR. However, DCR does provide a significant benefit in predicting the presence of nodule calcification. PMID- 27549085 TI - Differential impact of student behaviours on group interaction and collaborative learning: medical students' and tutors' perspectives. AB - BACKGROUND: Collaboration is of increasing importance in medical education and medical practice. Students' and tutors' perceptions about small group learning are valuable to inform the development of strategies to promote group dynamics and collaborative learning. This study investigated medical students' and tutors' views on competencies and behaviours which promote effective learning and interaction in small group settings. METHODS: This study was conducted at UNSW Australia. Five focus group discussions were conducted with first and second year medical students and eight small group tutors were interviewed. Data were transcribed verbatim and thematic analysis was conducted. RESULTS: Students and tutors identified a range of behaviours that influenced collaborative learning. The main themes that emerged included: respectfulness; dominance, strong opinions and openness; constructiveness of feedback; active listening and contribution; goal orientation; acceptance of roles and responsibilities; engagement and enthusiasm; preparedness; self- awareness and positive personal attributes. An important finding was that some of these student behaviours were found to have a differential impact on group interaction compared with collaborative learning. This information could be used to promote higher quality learning in small groups. CONCLUSION: This study has identified medical students' and tutors' perceptions regarding interactional behaviours in small groups, as well as behaviours which lead to more effective learning in those settings. This information could be used to promote learning in small groups. PMID- 27549086 TI - How do social activities mitigate informal caregivers' psychological distress? Evidence from a nine-year panel survey in Japan. AB - BACKGROUND: It is well known that informal caregiving negatively affects caregivers' mental health, while social activities improve mental health outcomes among middle-aged and elderly individuals. The goal of the present study was to examine how participation in social activities affected the trajectory of an informal caregiver's psychological distress. METHODS: We used the data from a nationwide nine-wave panel survey of the middle-aged individuals (aged 50-59 years at baseline) in Japan conducted in 2005-13 (N = 24,193 individuals;12,352 women and 11,841 men), mainly focusing on the respondents beginning to provide informal caregiving during the survey period. We employed linear mixed-effects models to explain how the trajectory of psychological distress, measured by Kessler 6 (K6) scores, was associated with caregiving commencement and duration, as well as social activity participation. RESULTS: Participation in social activities was associated with mitigated K6 scores at caregiving commencement by 66.2 and 58.2 % for women and men, respectively. After caregiving started, participation in social activities reduced the average rise in K6 scores, per year, by 65.6 and 89.6 % for women and men, respectively. We observed similar results when focusing on participation before caregiving commencement to avoid endogeneity problems. CONCLUSION: Results suggest that participation in social activities can alleviate caregivers' psychological distress. Policy measures to support social activities are recommended for the health and well-being of current and potential caregivers. PMID- 27549087 TI - Improving diagnosis of inherited peripheral neuropathies through gene panel analysis. AB - BACKGROUND: Inherited peripheral neuropathies (IPN) are the most common inherited neurological condition. It represents a highly heterogeneous group, both clinically and genetically. Targeted disease specific gene panel massively parallel sequencing (MPS) seems to be a useful tool in diagnosis of disorders with high genetic heterogeneity. METHODS: In our study, we have designed, validated and updated our own custom gene panel of all known genes associated with IPN. One hundred and ninety-eight patients have been tested so far. Only patients in whom mutations in more common causes or relevant genes have already been excluded were enrolled. Five consecutive panel designs were prepared according to recent literature search, the last one covering ninety-three genes. Each patient was tested only once. All data were evaluated with at least two different pipelines. RESULTS: In summary, causative mutation has been found in fifty-one patients (26 %). The results were inconclusive in thirty-one (16 %) patients. No variants of likely significance to IPN were found in one hundred and sixteen (58 %) patients. CONCLUSION: MPS gene panel enables testing of all known IPN causes at once with high coverage and at an affordable cost making it truly a method of choice also in IPN. Gene panel testing results in several interesting results and findings. PMID- 27549089 TI - Historical, morphological and clinical overview of placental site trophoblastic tumors: from bench to bedside. AB - INTRODUCTION: Placental site trophoblastic tumor (PSTT) is a form of gestational trophoblastic disease that originates from the implantation of an intermediate trophoblast. It was described for the first time by Von F. Marchand in 1895 as belonging to chorioepithelioma sui generis, a pathological condition with many variations and a progressive degree of malignancy. METHODS: We have conducted a literature review in MEDLINE about epidemiology, etiopathogenesis and clinical features of PSTT. Moreover, a case that occurred in our institution was reported. RESULTS: Our research has highlighted that existing published data about PSTT are not uniform. The number of cases described in the literature has updated and the clinical features of selected "case series" of patients diagnosed with PSTT were showed. The etiopathogenesis was discussed. It was noted that current prognostic factors still allow important information regarding PSTT to be obtained, albeit fragmentary. CONCLUSIONS: The lack of uniformity in data collection seen so far has limited full knowledge of PSTT. For this reason, we suggest a model (PSTT model) that collects and unifies PSTT evidence as this would be useful to identify worldwide precise prognostic factors, which are still lacking. When PSTT is diagnosed, the proper procedure seems to be total hysterectomy, with sampling of pelvic lymph nodes and ovarian conservation. For advanced-stage diseases, (stage III and IV) a combination of surgery and polychemotherapy is suggested. PMID- 27549088 TI - Actions of the antihistaminergic clemastine on presymptomatic SOD1-G93A mice ameliorate ALS disease progression. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a disease with a strong neuroinflammatory component sustained by activated microglia contributing to motoneuron death. However, how to successfully balance neuroprotective versus neurotoxic actions by the use of antinflammatory agents is still under scrutiny. We have recently shown that the antihistamine clemastine, an FDA-approved drug, can influence the M1/M2 switch occurring in SOD1-G93A ALS microglia. METHODS: Here, we have chronically treated female SOD1-G93A mice with clemastine, evaluated disease progression and performed mice lumbar spinal cord analysis at symptomatic and end stage of the disease. Moreover, we have studied the mechanism of action of clemastine in primary adult spinal SOD1-G93A microglia cultures and in NSC-G93A motor neuron-like cells. RESULTS: We found that a short treatment with clemastine (50 mg/kg) from asymptomatic (postnatal day 40) to symptomatic phase (postnatal day 120) significantly delayed disease onset and extended the survival of SOD1-G93A mice by about 10 %. Under these conditions, clemastine induced protection of motor neurons, modulation of inflammatory parameters, reduction of SOD1 protein levels and SQSTM1/p62 autophagic marker, when analysed immediately at the end of the treatment (postnatal day 120). A long treatment with clemastine (from asymptomatic until the end stage) instead failed to ameliorate ALS disease progression. At the end stage of the disease, we found that clemastine short treatment decreased microgliosis and SOD1 protein and increased LC3-II autophagic marker, while the long treatment produced opposite effects. Finally, in spinal microglia cultures from symptomatic SOD1-G93A mice clemastine activated inflammatory parameters, stimulated autophagic flux via the mTOR signalling pathway and decreased SOD1 levels. Modulation of autophagy was also demonstrated in NSC34 SOD1-G93A motor neuron-like cells. CONCLUSIONS: By gaining insights into the ameliorating actions of an antihistaminergic compound in ALS disease, our findings might represent an exploitable therapeutic approach for familial forms of ALS. PMID- 27549090 TI - Hypoxia-induced regulation of placental REDD1 and mTOR was impaired in a rat model of estrogen-induced cholestasis. AB - PURPOSE: Hypoxia inducible factor-1alpha (HIF-1alpha), regulated in development and DNA damage response-1 (REDD1), and mammalian target of rapamycin (mTOR) play distinct roles in response to hypoxia. The aim of this study was to evaluate whether the HIF-1alpha-REDD1-mTOR-mediated hypoxic stress response also operates normally in estrogen-induced cholestasis. METHODS: Pregnant rats were administered with ethinylestradiol (EE) to induce cholestasis and then were subjected to feto-placental ischemia reperfusion (IR); as controls, one group received neither EE nor IR, and another two groups received only EE or IR. RESULTS: Giving rats either EE alone or IR alone increased placental levels of HIF-1alpha, REDD1, glucose transporter-1 (GLUT1), and phosphoglycerate kinase-1 (PGK1), and decreased placental mTOR and lactic dehydrogenase A (LDHA) expression compared with the control rats. Subjecting EE-treated rats to IR did not further alter placental levels of REDD1 or mTOR, while it did elevate placental HIF 1alpha, GLUT1, and PGK1 expression, and decline LDHA expression. By contrast, mRNA levels did not differ significantly among the four groups for any of the proteins analyzed. CONCLUSIONS: This study manifested that placental HIF-1alpha and its downstream glucose metabolism effectors can effectively react to hypoxia in EE-induced cholestasis rats. However, hypoxia-induced REDD1 and mTOR alternation, which responds efficiently in normal placentas, was impaired in EE induced cholestasis placentas. PMID- 27549091 TI - Gonadotropin-releasing hormone agonist with add-back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis. AB - PURPOSE: This study was performed to compare the efficacy and tolerability of GnRH agonist with add-back therapy versus dienogest treatment for preventing pelvic pain recurrence after laparoscopic surgery for endometriosis. METHODS: Sixty-four reproductive-aged women who underwent laparoscopic surgery for endometriosis received post-operative medical treatment with either GnRH agonist plus 17beta-estradiol and norethisterone acetate (n = 28) or dienogest (n = 36) for 6 months. The pre- to post-treatment changes in pain were assessed using a visual analogue scale, and changes in quality-of-life and menopausal symptoms were measured by questionnaire. RESULTS: Visual analogue scale pain score decreased significantly for both treatments with no significant differences between groups. Neither physical, psychological, social, and environmental components of quality-of-life nor menopausal rating scale score were significantly different between the two groups. Bone mineral density at the lumbar spine declined significantly in both treatment groups (-2.5 % for GnRH agonist plus add-back and -2.3 % for dienogest), with no significant difference between the two groups. CONCLUSION: GnRH agonist and add-back therapy using 17beta-estradiol and norethisterone acetate are as effective and tolerable as dienogest for the prevention of pelvic pain recurrence after laparoscopic surgery for endometriosis. PMID- 27549092 TI - Prognostic factors in endometrial clear cell carcinoma. AB - OBJECTIVE: To document the experience regarding patients treated for endometrial clear cell carcinoma (ECCC), with reference to clinical, biochemical, histopathologic, and prognostic features. MATERIAL AND METHODS: Twenty-six ECCC patients, diagnosed and treated between 2008 and 2014, were reviewed retrospectively. From the hospital records, all data related to patients' demographic, clinical, biochemical, and histopathologic assessments and adjuvant therapy adjustments were evaluated. Disease-free survival (DFS), overall survival (OS), and 5-year cumulative survival rates (CSR) were estimated as well as prognostic factors associated with OS. RESULTS: The median follow-up time was 22.7 months, and the mean age at diagnosis was 64.0 years. Fourteen (53.8 %) women had early stage and 12 (46.2 %) women had advanced-stage disease. There were 17 (65.3 %) patients with pure clear cell carcinoma and 8 (30.7 %) patients with mixed histology on the hysterectomy specimen. Extra-uterine disease occurred more frequently in patients with pure ECCC and elevated CA-125 concentrations. Seventeen (65.3 %) patients received adjuvant platinum and taxane chemotherapy with (n: 13/17, 76.4 %) or without radiotherapy in the form of external beam radiotherapy (ERT) and/or vaginal brachytherapy (BRT). The rest of the patients (n: 9/26, 34.6 %), who had tumor with no or limited myometrial invasion without LVSI, impaired general health status, and non-compliance-to-post-operative treatment proposal received no adjuvant therapy. The mean DFS and OS were 49.54 and 50.01 months, respectively, with the 5-year CSR of 46.4 %. The mean OS was significantly shorter in patients with higher pre-operative CA-125 values, >2 cm tumor diameter, myometrial invasion >=1/2, cervical involvement, uterine serosal and/or adnexal invasion, lymph node metastasis, and, thus, with advanced-stage disease. Uterine serosal invasion was the only significant prognostic factor associated with OS in the multivariate analysis. CONCLUSION: Increased pre operative serum CA-125 levels are associated with advanced-stage disease, and uterine serosal involvement is a significant prognostic factor associated with OS in women with ECCC. PMID- 27549093 TI - Effect of glenoid concavity loss on shoulder stability- a case report in a professional wrestler. AB - BACKGROUND: Current glenoid defect measurement techniques only quantify bone loss in terms of defect diameter or surface. However, the glenoid depth plays an important role in shoulder stabilization by means of concavity compression. CASE PRESENTATION: We present a case of a professional wrestler who suffered from anterior shoulder instability after sustaining a bony Bankart lesion without loss of glenoid surface area but flattening of the concavity due to medialization of the fragment. The patient's glenoid concavity was reconstructed arthroscopically by reduction and percutaneous screw fixation of the bony fragment along with a capsulo-ligamentous shift. Changes of the glenoid concavity with according alterations in the Bony Shoulder Stability Ratio (BSSR) were analyzed on pre-op, post-op, and follow-up CT scans. Postoperative CT scans revealed a deepened concavity (3.3 mm) and improved BSSR (46.1 %) compared to pre-op scans (0.7 mm; 11.3 %). Follow-up CT scans showed a slight remodeling of the glenoid concavity (3.2 mm) with steady BSSR (44.7 %). CONCLUSION: This case shows that the passive stabilizing effect of the glenoid can be compromised by loss of concavity despite the absence of loss of articular surface. Therefore, addressing the concavity loss and resulting reduction of the BSSR is recommended in these cases. Bony Bankart repair was successful in restoring the BSSR of the patients shoulder as determined by mathematical calculations based on CT scans. PMID- 27549094 TI - Diagnostic value of 3.0T (1)H MRS with choline-containing compounds ratio (?CCC) in primary malignant hepatic tumors. AB - BACKGROUND: The purpose of this study was to investigate the diagnostic value of 3.0-T (1)H magnetic resonance spectroscopy ((1)H MRS) in primary malignant hepatic tumors and to compare the effects of (1)H MRS on the diagnostic accuracy of liver-occupying lesions between junior and experienced radiologists. METHODS: This study included 50 healthy volunteers and 40 consecutive patients (50 lesions). Informed consent was obtained from each subject. Images were obtained on clinical whole-body 3.0-T MR system. Point -Resolved Spectroscopy was used to obtain the spectroscopy image. All conventional images were reviewed blindly by junior radiologist and experienced radiologist, respectively. The choline containing compounds peak area (CCC-A) was measured with SAGE software, and the choline-containing compound ratio (?CCC) was calculated. The efficacy of CCC-A and ?CCC in the diagnosis of primary malignant hepatic tumors was determined by plotting receiver operating characteristic (ROC) curves. We also compared the effects of MRS on the diagnostic accuracy of liver-occupying lesions with junior and experienced radiologist. RESULTS: A significant increase in mean CCC-A was observed in malignant tumors compared with benign tumors. The ROC curve showed ?CCC had a high discriminatory ability in diagnosing primary malignant hepatic tumors with a sensitivity and specificity of 94.3 and 93.3 %, respectively. The ?CCC area under the curve (AUC) was 0.97 that was larger than that of both junior and experienced radiologist, while the significantly statistical difference was only obtained between ?CCC and junior radiologist (P = 0.01). CONCLUSION: (1)H MRS with ?CCC demonstrates good efficacy in diagnosing primary malignant hepatic tumors. The technique improves the accuracy of diagnosing liver-occupying lesions, particularly for junior radiologists. PMID- 27549095 TI - Spatiotemporal analysis of dengue fever in Nepal from 2010 to 2014. AB - BACKGROUND: Due to recent emergence, dengue is becoming one of the major public health problems in Nepal. The numbers of reported dengue cases in general and the area with reported dengue cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of dengue have not been investigated yet. This study aims to fill this gap by analyzing spatiotemporal patterns based on monthly surveillance data aggregated at district. METHODS: Dengue cases from 2010 to 2014 at district level were collected from the Nepal government's health and mapping agencies respectively. GeoDa software was used to map crude incidence, excess hazard and spatially smoothed incidence. Cluster analysis was performed in SaTScan software to explore spatiotemporal clusters of dengue during the above-mentioned time period. RESULTS: Spatiotemporal distribution of dengue fever in Nepal from 2010 to 2014 was mapped at district level in terms of crude incidence, excess risk and spatially smoothed incidence. Results show that the distribution of dengue fever was not random but clustered in space and time. Chitwan district was identified as the most likely cluster and Jhapa district was the first secondary cluster in both spatial and spatiotemporal scan. July to September of 2010 was identified as a significant temporal cluster. CONCLUSION: This study assessed and mapped for the first time the spatiotemporal pattern of dengue fever in Nepal. Two districts namely Chitwan and Jhapa were found highly affected by dengue fever. The current study also demonstrated the importance of geospatial approach in epidemiological research. The initial result on dengue patterns and risk of this study may assist institutions and policy makers to develop better preventive strategies. PMID- 27549096 TI - Poorly controlled gout: who is doing poorly? AB - Gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals, is commonly seen in primary care and specialist clinics. In recent years, there has been a resurgence of interest in gout due to advances in therapies and the understanding of pathophysiology, with new guidelines being published by international bodies. However, there is still a gap between the goals of treatment and actual day-to-day practice. Barriers that result in poorly controlled gout include patient factors such as lack of understanding of the disease, stigma and nonadherence to treatment, as well as physician factors such as knowledge gaps, inadequate use of allopurinol and lack of ownership of the disease. The medical profession needs to do more to bridge the gap through physician and patient education, identification of treatment targets with appropriate use of drugs, and dissemination of guidelines. PMID- 27549097 TI - Alzheimer's Drug Discovery Maze: A Snap View of the Past Decade's Diverse Pharmacological Targets for the Disorder. AB - The discovery of disease modifying anti-Alzheimer's molecules continues to be dared by: disease target multiplicity, downstream neurodegenerative biochemistry complexities, and genotype implications. A confluence of the above ingredients has contributed to a pipeline of creative molecules that regrettably underperform in clinical trials. Thus far, only five palliative pharmacotherapeutic agents, that is, four acetylcholine potentiating agents and an N-methyl-D-aspartate (NMDA) antagonist are clinically available. In this review we collectively describe the currently suggested targetable pathways for designing anti Alzheimer's agents (palliative and/or disease modifying). We are prompted to contribute in this manner out of a desire to simplify and consolidate, to a certain extent, the divergent target literature on Alzheimer's drug discovery. We herein provide a summary update and perspective on realized and potentially druggable pharmacological targets for this CNS disorder. This article covers mostly the 2005-2015 medicinal chemistry/pharmacological/biological literature space on the subject. PMID- 27549098 TI - Discovery and Development of Topoisomerase Inhibitors as Anticancer Agents. AB - As one of the leading causes of deaths worldwide, cancer is posing threat despite efforts being taken to develop effective anticancer drugs. There is an increase in number of chemotherapy treatments due to growing number of manifestations causing increasing toxicities of cytotoxic agents. Almost all the anticancer agents available till date have one or the other side effects. Topoisomerases are the attractive targets to develop effective anticancer agents. There has been development of many topoisomerase inhibitors till date and has shown good anticancer activity but their side effects outnumber their anticancer potential. Hence, there is an urgent need to develop effective therapeutic agents with fewer side effects. This review deals with design and development aspect of topoisomerase inhibitors as exciting novel anticancer agents. The emphasis has been laid in particular on the new potential heterocyles as TOP inhibitors in the field of medicinal chemistry. The review discusses about the topoisomerase poisons, TOP1 suppressors, TOP inhibitors and Dual TOP 1/2 inhibitors. PMID- 27549099 TI - Talking to the dead: using Post-mortem data in the assessment of stress in tiger sharks (Galeocerdo cuvier) (Peron and Lesueur, 1822). AB - Sharks are very sensitive to stress and prone to a high mortality rate after capture. Since approximately 50 million of sharks are caught as bycatch every year, and current recommendations to reduce the impact of commercial fishing strongly support immediate release, it is imperative to better understand post release mortality caused by the stress of capture and handling. Blood samples allow the assessment of stress levels which are valuable tools to reduce mortality in commercial, recreational and scientific fishing, being essential for the improvement in those conservation measures. Biochemical analyses are widely used for sharks as stress indicators, with secondary plasma parameters (lactate, glucose and ions) being the most often employed assays. However, it is virtually impossible to determine baseline plasma parameters in free-ranging sharks, since blood withdrawal involves animal capture and restrain, which are stressful procedures. This study aims at analyzing secondary parameters of five healthy tiger sharks captured with circular hooks and handlines in Fernando de Noronha (Northeastern Brazil) and comparing them with secondary parameters of three dead tiger sharks caught off Recife (also Northeastern Brazil). The results showed that the analysis of some plasma constituents in dead animals may be an efficient tool to assess stress and lethality. However, traditional parameters such as glucose and calcium, need to be used with caution. The results also demonstrated the extreme importance of urea and phosphorus for assessing stress response and mortality in tiger sharks, both parameters frequently neglected and of utmost importance for shark's homeostasis. PMID- 27549100 TI - Findings of ulceration and severe stricture on MRE can predict prognosis of Crohn's disease in patients treated with anti-TNF treatment. AB - BACKGROUND: MR enterography (MRE) is useful for evaluating transmural lesions and extra-intestinal complications of Crohn's disease (CD). The aim of this study was to prospectively evaluate whether MRE could detect severe strictures and inflammatory lesions in patients who lost the responsiveness to anti-TNF treatment and whether MRE could predict prognosis of CD patients with clinical remission. PATIENTS AND METHODS: MRE were conducted in 50 patients who were treated with infliximab or adalimumab. The main aims of this study were as follows; (1) to compare the rates of CD lesions of the patients with clinical remission and active disease at the baseline and (2) to assess the MRE findings that were predictors of clinical recurrence among patients with clinical remission at the baseline. RESULTS: The MRE detection rates of markedly increased contrast uptake, severe strictures, and the presence of ulcers were significantly higher in patients with Crohn Disease Activity Index >=150 than in patients with clinical remission. Over a mean follow-up of 18.2 months, the absence of ulceration (p = 0.001) or severe stricture (p = 0.01) prolonged clinical recurrence among patients with clinical remission at baseline. Expected duration of recurrence significantly prolonged in patients with total magnetic resonance index of activity (MaRIA) <36.3 [29.8 months (95% CI 23.7-35.9)] than in patients with total MaRIA >=36.3 (13.9 months (95% CI 7.7-20.1). A cut-off value of total MaRIA score of 36.3 had a sensitivity of 75% and specificity of 70% for predicting recurrence. CONCLUSION: Findings of ulceration and severe stricture on MRE predict prognosis of CD patients who were treated with anti-TNF treatment. MRE might be useful for making treatment decisions in patients who lost the effectiveness of medical treatments. PMID- 27549101 TI - Frequency and reasons for extra sequences in clinical abdominal MRI examinations. AB - PURPOSE: The purpose of the study was to identify the frequency and reasons for extra sequences in clinical liver MRI and MRCP examinations. METHODS: A total of 250 consecutive liver MRI and 250 consecutive MRCP examinations performed at a single institution were reviewed. Extra sequences performed in comparison with our standard institutional protocol were identified. Reasons for the extra sequences were identified. Overall trends were assessed. RESULTS: In significantly greater fractions of exams (p = 0.009-0.030), MRCP had >=1 extra sequence (40.8% vs. 29.2%) and >=2 extra sequences (16.0% vs. 5.6%) in comparison with the institutional protocol than did liver MRI. The average number of extra sequences was significantly higher (p = 0.004) for MRCP (0.73 +/- 1.2) than liver MRI (0.44 +/- 0.88). Reasons for extra sequences were as follows: sequence repeated for patient motion (33.8% for liver MRI; 31.9% for MRCP); sequence repeated for anatomic coverage (24.3% for liver MRI; 19.8% for MRCP); sequence added by the radiologist (15.3% for liver MRI; 33.0% for MRCP); sequence repeated for other reason (17.1% for liver MRI; 12.6% for MRCP); and sequence added by the technologist (5.4% for liver MRI; 2.7% for MRCP). The most commonly repeated sequence due to motion was the axial fat-saturated turbo spin-echo T2-weighted sequence for both liver MRI and MRCP (54.7% and 29.3% of sequences repeated due to motion, respectively). CONCLUSION: For liver MRI and MRCP exams, sequences were most often repeated due to motion artifact (most often occurring on TSE T2WI), and sequences were most often added by the radiologist. The findings may help guide sequence optimization, quality improvement initiatives, and standardization of operations, for improving efficiency in abdominal MRI workflow. PMID- 27549102 TI - Author's reply to da Mota and Marocolo: "The Effects of Ischemic Preconditioning on Human Exercise Performance: a Counterpoint". PMID- 27549103 TI - Authors' Reply to Wang: "On Magnetic Resonance Imaging of Intervertebral Disc Ageing". PMID- 27549104 TI - Prevalence of sleep-disordered breathing in acute coronary syndrome: a systemic review and meta-analysis. AB - PURPOSE: This study aimed to review the literature on the prevalence of sleep disordered breathing (SDB) in patients with acute coronary syndrome (ACS). METHODS: Relevant studies were searched on PubMed, EMBASE, and Cochrane Library through December 2014. Data were extracted using standardized forms. Pooled prevalence of all SDB (apnea-hypopnea index (AHI) > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30) in ACS patients was calculated using DerSimonian-Laird random-effects model. Sensitivity analysis was performed based on races and diagnostic methods of SDB. RESULTS: A total of 32 studies were included in the present meta-analysis, examining 3360 patients. The meta-analysis indicated that pooled prevalence of all SDB (AHI > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30) in ACS patients were 69 % (95 % confidence interval (CI) = 61, 77 %), 43 % (95 % CI = 36, 49 %), and 25 % (95 % CI = 17, 33 %), respectively. Sensitivity analysis indicated that the pooled prevalence of SDB in Western population was similar to that in Asian population. However, diagnostic methods of SDB seemed to have various impacts on the prevalence of all SDB (AHI > 5), moderate-to-severe SDB (AHI > 15), and severe SDB (AHI > 30). CONCLUSIONS: High prevalence of all SDB, moderate-to-severe SDB, and severe SDB was found in ACS patients. It is clinically important to screen for SDB in patients with ACS. PMID- 27549105 TI - Examining the Prevalence Rates of Preexisting Maternal Medical Conditions and Pregnancy Complications by Source: Evidence to Inform Maternal and Child Research. AB - Objectives We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research. Methods Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic (k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS. Results GHD was under-ascertained on birth certificates (5.7 %) and more frequently indicated by maternal report (11 %) and discharge data (8.2 %). PROM was indicated more on birth certificates (7.4 %) than maternal report (4.5 %) or discharge data (5.7 %). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor (kappa < 0.4) to moderate (0.4 <= kappa < 0.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment (kappa = 0.79, 95 % CI 0.74, 0.85). Conclusions for Practice Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life course. PMID- 27549106 TI - Human barrier models for the in vitro assessment of drug delivery. AB - In vitro test systems gain increasing importance in preclinical studies to increase the predictivity and reduce animal testing. Of special interest herein are barrier tissues that guard into the human body. These barriers are formed by highly specialized tissues such as the skin, the airways, and the intestine. However, to recapitulate these tissues, researchers are currently restricted by a lack of suitable supporting scaffolds. In this study, we present biological scaffolds based on decellularized porcine gut segments that offer a natural environment for cell growth and differentiation. Employing these scaffolds, human barrier models of the skin, the airways, and the intestine that mimic the natural histological architecture of the respective tissue are generated. These models show tissue specific barrier properties, such as the stratification of the skin, the mucociliary phenotype of the airways, and polarization of the intestinal epithelium. To investigate the transport characteristics of the intestinal test system, we incubated the tissue models with fluorescein (P app <1 * 106 cm/s), propranolol (P app >7 * 106 cm/s), and rhodamin123 (ratio 2.45). The here presented biological scaffolds facilitate the in vitro generation of human barrier models that might represent useful tools for drug delivery studies. PMID- 27549107 TI - In vitro bioassay model for screening non-viral neurotrophic factor gene delivery systems for glaucoma treatment. AB - The feasibility of a two-layer contact-independent 3D neuronal co-culture model to test the bioactivity of brain-derived neurotrophic factor (BDNF), produced by non-virally transfected A7 astrocytes (trA7), on neurite growth in a second cell population of SH-SY5Y (CRL-2266) neuroblastoma cells with (oxSH-SY5Y) or without oxidative damage (SH-SY5Y) was evaluated. Transfection of A7 astrocytes was carried out with BDNF-encoding plasmid using K2(r) nanoparticle gene delivery system (K2-NPs). The physicochemical characteristics of K2-NPs, transfection efficiency, and BDNF production were evaluated using dynamic light scattering, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), respectively. Neurite counts and length measurements were performed after anti-neuron-specific beta-III tubulin antibody immunostaining using confocal laser scanning microscopy. Transfection efficiency of A7 astrocytes by K2-NPs (diameter 83.9 +/- 0.4 nm, zeta potential +57.3 +/- 2.8 mV) was 39.5 +/- 4.6 % with cell viability of 73 +/- 2 %. BDNF levels produced were 3750.8 +/- 251.1, 9052.6 +/- 1391.2, and 10,367.1 +/- 390.8 pg/mL at 24, 48, and 72 h, respectively. The increased number of neurites with higher neurite lengths confirmed the bioactivity of BDNF secreted from the transfected A7 astrocytes over 72 h. Neurite count comparisons showed that both trA7/oxSH-SY5Y and trA7/SH-SY5Y consistently produced higher neurite counts compared to A7/oxSH-SY5Y and oxSH-SY5Y only experimental conditions. The results of this study demonstrate that neurite outgrowth quantitation in astrocyte-SH-SY5Y cell co-culture is a suitable bioassay model for evaluating non-viral gene delivery systems. Furthermore, it also demonstrates a proof-of-concept for nanoparticle-based neurotrophic factor gene delivery to astrocytes and stimulation of neurite outgrowth. PMID- 27549108 TI - Bloodstream infections caused by Escherichia coli producing AmpC beta-lactamases: epidemiology and clinical features. AB - The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC beta-lactamases (AmpC-Ec-BSI). In a multi-centre case-control study, all third-generation cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla AmpC (bla ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla AmpC (bla c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla ac-AmpC and six were bla c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p < 0.05) and presented more intrinsic and extrinsic risk factors. At least one risk factor was present in 94.1 % of cases vs. 41.7 % of controls (p = 0.002). Severity and length of stay (LOS) were higher among cases (mean Pitt Score 2.6 vs. 0.38 in controls, p = 0.03; LOS 17.5 days vs. 6 in controls, p = 0.02). Inappropriate empirical therapy (IET) was administered to 70.6 % of cases and 23.5 % of controls (p < 0.003). No differences were found in terms of cure rate at the 14th day and mortality. Bloodstream infections due to AmpC-Ec (mostly plasmid-mediated) are infrequent in our area. AmpC-Ec-BSI affects mainly patients with intrinsic risk factors and those with previous antibiotic exposure. A high proportion received IET. PMID- 27549109 TI - Direct matrix-assisted laser desorption ionisation time-of-flight mass spectrometry identification of mycobacteria from colonies. AB - Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) identification of mycobacteria requires a standard acetonitrile/formic acid pre-MALDI-TOF-MS. We prospectively compared this standard protocol with direct deposit with matrix for the identification of mycobacteria cultured on solid media. We first verified that Mycobacterium tuberculosis was killed after it was mixed with matrix. Then, 111 Mycobacterium isolates previously identified by partial rpoB gene sequencing were tested in parallel by the two protocols. An identification score >1.7 was obtained in 86/111 (77.5 %) isolates after protein extraction versus 97/111 (87.4 %) isolates after direct deposit (p = 0.039, Chi-squared test). In a third step, we determined that direct deposit achieved identification for as few as 2.104 M. tuberculosis organisms. In a fourth step, we evaluated direct deposit of one colony for 116 solid medium-cultured clinical isolates finally identified as representative of 12 species (63.8 % M. tuberculosis). For 114/116 (98.3 %) isolates with an identification score >1.2, the MALDI-TOF-MS identification was in complete agreement with the reference rpoB gene sequencing identification. One isolate with a MALDI-TOF-MS identification score of 1.22 for M. fortuitum was identified as M. avium by partial rpoB gene sequencing. One other isolate with a MALDI-TOF-MS identification score of 1.22 for M. tuberculosis was identified as M. tuberculosis by genotyping. All the original MALDI-TOF-MS spectra reported here have been deposited in a public database. Direct deposit of one colony on a MALDI-TOF-MS plate allows for an accurate identification of mycobacteria for an identification score >1.3. PMID- 27549110 TI - Taking Telemedicine to the Next Level in Diabetes Population Management: a Review of the Endo ECHO Model. AB - Worldwide increases in diabetes prevalence in the face of limited medical resources have prompted international interest in innovative healthcare delivery models. Project ECHO (Extension for Community Healthcare Outcomes) is a "telementoring" program which has been shown to increase capacity for complex disease management in medically underserved regions. In contrast to a traditional telemedicine model which might connect a specialist with one patient, the ECHO model allows for multiple patients to benefit simultaneously by building new expertise. We recently applied the ECHO model to improve health outcomes of patients with complex diabetes (Endo ECHO) living in rural New Mexico. We describe the design of the Endo ECHO intervention and a 4-year, prospective program evaluation assessing health outcomes, utilization patterns, and cost effectiveness. The Endo ECHO evaluation will demonstrate whether and to what extent this intervention improves outcomes for patients with complex diabetes living in rural New Mexico, and will serve as proof-of-concept for academic medical centers wishing to replicate the model in underserved regions around the world. PMID- 27549111 TI - QTL analysis for chalkiness of rice and fine mapping of a candidate gene for qACE9. AB - BACKGROUND: An ideal appearance is of commercial value for rice varieties. Chalkiness is one of the most important appearance quality indicators. Therefore, clarification of the heredity of chalkiness and its molecular mechanisms will contribute to reduction of rice chalkiness. Although a number of QTLs related to chalkiness were mapped, few of them have been cloned so far. RESULTS: In this study, using recombinant inbred lines (RILs) of PA64s and 9311, we identified 19 QTLs associated with chalkiness on chromosomes 1, 4, 6, 7, 9 and 12, which accounted for 5.1 to 30.6 % of phenotypic variations. A novel major QTL qACE9 for the area of chalky endosperm (ACE) was detected in Hainan and Hangzhou, both mapped in the overlapping region on chromosome 9. It was further fine mapped to an interval of 22 kb between two insertion-deletion (InDel) markers IND9-4 and IND9-5 using a BC4F2 population. Gene prediction analysis identified five putative genes, among which only one gene (OsAPS1), whose product involved in starch synthesis, was detected two nucleotide substitutions causing amino acid change between the parents. Significant difference was found in apparent amylose content (AAC) between NILqACE9 and 9311. And starch granules were round and loosely packed in NILqACE9 compared with 9311 by scanning electron microscopy (SEM) analysis. CONCLUSIONS: OsAPS1 was selected as a novel candidate gene for fine-mapped qACE9. The candidate gene not only plays a critical role during starch synthesis in endosperm, but also determines the area of chalky endosperm in rice. Further cloning of the QTL will facilitate the improvement of quality in hybrid rice. PMID- 27549112 TI - Epigenetic mutagen as histone modulator can be detected by yeast flocculation. AB - We have previously reported that flocculation of a yeast co-transformed with the human DNA methyltransferase 1 (DNMT1) and DNMT3B genes was inhibited by DNMT inhibitors. It is well known that epigenetic mutagens can disturb nucleosome positioning via DNA methylation and/or histone modification. In this study we first examined the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the flocculation level of yeast. TSA dose-dependently promoted the flocculation exhibited by the yeast transformed with the DNMT genes or empty vectors. Furthermore, TSA induced the expression of the flocculin-encoding gene FLO1 The anthracene-derived alizarin, a natural madder root dye, has a potential for carcinogenesis promotion; however, the mode of action has not been elucidated. It is considered that epigenetic changes can promote cancer. Alizarin but not anthracene enhanced the flocculation level of the yeast. Similar to TSA, alizarin also upregulated FLO1 mRNA. Surprisingly, western blotting indicated that alizarin, but not anthracene, reduced the level of histone H3 in yeast, and alizarin-treated cells frequently displayed abnormally shaped nuclei. These findings suggest that alizarin uniquely influences nucleosome structure. Taken together with our previous findings, this study suggests that the DNMT gene transformed yeast strains are a useful tool for screening various classes of epigenetic mutagens. PMID- 27549113 TI - Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation. AB - Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1beta (IL-1beta) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3* per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R dependent pulmonary inflammation with airway hyperreactivity in mice. PMID- 27549114 TI - Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury. AB - Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110gamma, phospho-Akt, phospho-NF-kappaB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-kappaB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury. PMID- 27549115 TI - RNA-Seq reveals virus-virus and virus-plant interactions in nature. AB - As research on plant viruses has focused mainly on crop diseases, little is known about these viruses in natural environments. To understand the ecology of viruses in natural systems, comprehensive information on virus-virus and virus-host interactions is required. We applied RNA-Seq to plants from a natural population of Arabidopsis halleri subsp. gemmifera to simultaneously determine the presence/absence of all sequence-reported viruses, identify novel viruses and quantify the host transcriptome. By introducing the criteria of read number and genome coverage, we detected infections by Turnip mosaic virus (TuMV), Cucumber mosaic virus and Brassica yellows virus Active TuMV replication was observed by ultramicroscopy. De novo assembly further identified a novel partitivirus, Arabidopsis halleri partitivirus 1 Interestingly, virus reads reached a maximum level that was equivalent to that of the host's total mRNA, although asymptomatic infection was common. AhgAGO2, a key gene in host defence systems, was upregulated in TuMV-infected plants. Multiple infection was frequent in TuMV infected leaves, suggesting that TuMV facilitates multiple infection, probably by suppressing host RNA silencing. Revealing hidden plant-virus interactions in nature can enhance our understanding of biological interactions and may have agricultural applications. PMID- 27549116 TI - Soil and leaf litter metaproteomics-a brief guideline from sampling to understanding. AB - The increasing application of soil metaproteomics is providing unprecedented, in depth characterization of the composition and functionality of in situ microbial communities. Despite recent advances in high-resolution mass spectrometry, soil metaproteomics still suffers from a lack of effective and reproducible protein extraction protocols and standardized data analyses. This review discusses the opportunities and limitations of selected techniques in soil-, and leaf litter metaproteomics, and presents a step-by-step guideline on their application, covering sampling, sample preparation, extraction and data evaluation strategies. In addition, we present recent applications of soil metaproteomics and discuss how such approaches, linking phylogenetics and functionality, can help gain deeper insights into terrestrial microbial ecology. Finally, we strongly recommend that to maximize the insights environmental metaproteomics may provide, such methods should be employed within a holistic experimental approach considering relevant aboveground and belowground ecosystem parameters. PMID- 27549117 TI - Structural Basis of Intracellular TGF-beta Signaling: Receptors and Smads. AB - Stimulation of the transforming growth factor beta (TGF-beta) family receptors activates an intracellular phosphorylation-dependent signaling cascade that culminates in Smad transcriptional activation and turnover. Structural studies have identified a number of allosteric mechanisms that control the localization, conformation, and oligomeric state of the receptors and Smads. Such mechanisms dictate the ordered binding of substrate and adaptor proteins that determine the directionality of the signaling process. Activation of the pathway has been illustrated by the various structures of the receptor-activated Smads (R-Smads) with SARA, Smad4, and YAP, respectively, whereas mechanisms of down-regulation have been elucidated by the structural complexes of FKBP12, Ski, and Smurf1. Interesting parallels have emerged between the R-Smads and the Forkhead associated (FHA) and interferon regulatory factor (IRF)-associated domains, as well as the Hippo pathway. However, important questions remain as to the mechanism of Smad-independent signaling. PMID- 27549120 TI - Nested partially latent class models for dependent binary data; estimating disease etiology. AB - The Pneumonia Etiology Research for Child Health (PERCH) study seeks to use modern measurement technology to infer the causes of pneumonia for which gold standard evidence is unavailable. Based on case-control data, the article describes a latent variable model designed to infer the etiology distribution for the population of cases, and for an individual case given her measurements. We assume each observation is drawn from a mixture model for which each component represents one disease class. The model conisidered here addresses a major limitation of the traditional latent class approach by taking account of residual dependence among multivariate binary outcomes given disease class, hence reducing estimation bias, retaining efficiency and offering more valid inference. Such "local dependence" on each subject is induced in the model by nesting latent subclasses within each disease class. Measurement precision and covariation can be estimated using the control sample for whom the class is known. In a Bayesian framework, we use stick-breaking priors on the subclass indicators for model averaged inference across different numbers of subclasses. Assessment of model fit and individual diagnosis are done using posterior samples drawn by Gibbs sampling. We demonstrate the utility of the method on simulated and on the motivating PERCH data. PMID- 27549119 TI - Systematic review of management strategies to control chronic wasting disease in wild deer populations in North America. AB - BACKGROUND: Chronic wasting disease (CWD) is a contagious, fatal prion disease affecting cervids in a growing number of regions across North America. Projected deer population declines and concern about potential spread of CWD to other species warrant strategies to manage this disease. Control efforts to date have been largely unsuccessful, resulting in continuing spread and increasing prevalence. This systematic review summarizes peer-reviewed published reports describing field-applicable CWD control strategies in wild deer populations in North America using systematic review methods. Ten databases were searched for peer-reviewed literature. Following deduplication, relevance screening, full-text appraisal, subject matter expert review and qualitative data extraction, nine references were included describing four distinct management strategies. RESULTS: Six of the nine studies used predictive modeling to evaluate control strategies. All six demonstrated one or more interventions to be effective but results were dependant on parameters and assumptions used in the model. Three found preferential removal of CWD infected deer to be effective in reducing CWD prevalence; one model evaluated a test and slaughter strategy, the other selective removal of infected deer by predators and the third evaluated increased harvest of the sex with highest prevalence (males). Three models evaluated non selective harvest of deer. There were only three reports that examined primary data collected as part of observational studies. Two of these studies supported the effectiveness of intensive non-selective culling; the third study did not find a difference between areas that were subjected to culling and those that were not. Seven of the nine studies were conducted in the United States. CONCLUSIONS: This review highlights the paucity of evaluated, field-applicable control strategies for CWD in wild deer populations. Knowledge gaps in the complex epidemiology of CWD and the intricacies inherent to prion diseases currently pose significant challenges to effective control of this disease in wild deer in North America. PMID- 27549121 TI - Nonparametric overdose control with late-onset toxicity in phase I clinical trials. AB - Under the framework of Bayesian model selection, we propose a nonparametric overdose control (NOC) design for dose finding in phase I clinical trials. Each dose assignment is guided via a feasibility bound, which thereby can control the number of patients allocated to excessively toxic dose levels. Several aspects of the NOC design are explored, including the coherence property in dose assignment, calibration of design parameters, and selection of the maximum tolerated dose (MTD). We further propose a fractional NOC (fNOC) design in conjunction with a so called fractional imputation approach, to account for late-onset toxicity outcomes. Extensive simulation studies have been conducted to show that both the NOC and fNOC designs have robust and satisfactory finite-sample performance compared with the existing dose-finding designs. The proposed methods also possess several desirable properties: treating patients more safely and also neutralizing the aggressive escalation to overly toxic doses when the toxicity outcomes are late-onset. The fNOC design is exemplified with a real cancer phase I trial. PMID- 27549118 TI - Aggregation and Prion-Like Properties of Misfolded Tumor Suppressors: Is Cancer a Prion Disease? AB - Prion diseases are disorders that share several characteristics that are typical of many neurodegenerative diseases. Recently, several studies have extended the prion concept to pathological aggregation in malignant tumors involving misfolded p53, a tumor-suppressor protein. The aggregation of p53 and its coaggregation with p53 family members, p63 and p73, have been shown. Certain p53 mutants exert a dominant-negative regulatory effect on wild-type (WT) p53. The basis for this dominant-negative effect is that amyloid-like mutant p53 converts WT p53 into an aggregated species, leading to a gain-of-function (GoF) phenotype and the loss of its tumor-suppressor function. Recently, it was shown that p53 aggregates can be internalized by cells and can coaggregate with endogenous p53, corroborating the prion-like properties of p53 aggregates. The prion-like behavior of oncogenic p53 mutants provides an explanation for its dominant-negative and GoF properties, including the high metastatic potential of cancer cells carrying p53 mutations. The inhibition of p53 aggregation appears to represent a promising target for therapeutic intervention in patients with malignant tumors. PMID- 27549122 TI - Integrative clustering of multi-level omics data for disease subtype discovery using sequential double regularization. AB - With the rapid advances in technologies of microarray and massively parallel sequencing, data of multiple omics sources from a large patient cohort are now frequently seen in many consortium studies. Effective multi-level omics data integration has brought new statistical challenges. One important biological objective of such integrative analysis is to cluster patients in order to identify clinically relevant disease subtypes, which will form basis for tailored treatment and personalized medicine. Several methods have been proposed in the literature for this purpose, including the popular iCluster method used in many cancer applications. When clustering high-dimensional omics data, effective feature selection is critical for better clustering accuracy and biological interpretation. It is also common that a portion of "scattered samples" has patterns distinct from all major clusters and should not be assigned into any cluster as they may represent a rare disease subcategory or be in transition between disease subtypes. In this paper, we firstly propose to improve feature selection of the iCluster factor model by an overlapping sparse group lasso penalty on the omics features using prior knowledge of inter-omics regulatory flows. We then perform regularization over samples to allow clustering with scattered samples and generate tight clusters. The proposed group structured tight iCluster method will be evaluated by two real breast cancer examples and simulations to demonstrate its improved clustering accuracy, biological interpretation, and ability to generate coherent tight clusters. PMID- 27549124 TI - Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas. AB - Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2. T cells engineered to express a third-generation GD2-CAR incorporating the 14g2a-scFv with the CD28, OX40, and CD3zeta signaling domains (14g2a.CD28.OX40.zeta) mediated efficient and comparable lysis of both GD2+ sarcoma and neuroblastoma cell lines in vitro However, in xenograft models, GD2 CAR T cells had no antitumor effect against GD2+ sarcoma, despite effectively controlling GD2+ neuroblastoma. We observed that pediatric sarcoma xenografts, but not neuroblastoma xenografts, induced large populations of monocytic and granulocytic murine myeloid-derived suppressor cells (MDSC) that inhibited human CAR T-cell responses in vitro Treatment of sarcoma-bearing mice with all-trans retinoic acid (ATRA) largely eradicated monocytic MDSCs and diminished the suppressive capacity of granulocytic MDSCs. Combined therapy using GD2-CAR T cells plus ATRA significantly improved antitumor efficacy against sarcoma xenografts. We conclude that retinoids provide a clinically accessible class of agents capable of diminishing the suppressive effects of MDSCs, and that co administration of retinoids may enhance the efficacy of CAR therapies targeting solid tumors. Cancer Immunol Res; 4(10); 869-80. (c)2016 AACR. PMID- 27549123 TI - VEGF Neutralization Plus CTLA-4 Blockade Alters Soluble and Cellular Factors Associated with Enhancing Lymphocyte Infiltration and Humoral Recognition in Melanoma. AB - Immune recognition of tumor targets by specific cytotoxic lymphocytes is essential for the effective rejection of tumors. A phase I clinical trial of ipilimumab (an antibody that blocks CTLA-4 function) in combination with bevacizumab (an antibody that inhibits angiogenesis) in patients with metastatic melanoma found favorable clinical outcomes were associated with increased tumor endothelial activation and lymphocyte infiltration. To better understand the underlying mechanisms, we sought features and factors that changed as a function of treatment in patients. Ipilimumab plus bevacizumab (Ipi-Bev) increased tumor vascular expression of ICAM1 and VCAM1. Treatment also altered concentrations of many circulating cytokines and chemokines, including increases of CXCL10, IL1alpha, TNFalpha, CXCL1, IFNalpha2, and IL8, with decreases in VEGF-A in most patients. IL1alpha and TNFalpha induced expression of E-selectin, CXCL1, and VCAM1 on melanoma tumor-associated endothelial cells (TEC) in vitro and promoted adhesion of activated T cells onto TEC. VEGFA inhibited TNFalpha-induced expression of ICAM1 and VCAM1 and T-cell adhesion, which was blocked by bevacizumab. CXCL10 promoted T-cell migration across TEC in vitro, was frequently expressed by melanoma cells, and was upregulated in a subset of tumors in treated patients. Robust upregulation of CXCL10 in tumors was accompanied by increased T cell infiltration. Ipi-Bev also augmented humoral immune responses recognizing targets in melanoma, tumor endothelial, and tumor mesenchymal stem cells. Our findings suggest that Ipi-Bev therapy augments immune recognition in the tumor microenvironment through enhancing lymphocyte infiltration and antibody responses. IL1alpha, TNFalpha, and CXCL10, together with VEGF neutralization, contribute to Ipi-Bev-induced melanoma immune recognition. Cancer Immunol Res; 4(10); 858-68. (c)2016 AACR. PMID- 27549125 TI - The clinical value of adipokines in predicting the severity and outcome of acute pancreatitis. AB - BACKGROUND: Recent data shows that patients with severe acute pancreatic might benefit from early intensive therapy, enteral nutrition and timely transfer to specialized centers. The early prophylactic use of antibiotics in AP remains controversial. The role and need for new markers in stratification of acute pancreatitis is also uncertain. This study aims to evaluate the prognostic usefulness of adipokines in prediction of the severity and outcome of acute pancreatitis (AP). METHODS: Prospective study was conducted in four clinical centers. The diagnosis and severity assessment of AP was established according to the revised 2012 Atlanta classification. Adipokines, IL-6 and CRP levels were measured at admission and on 3rd day of hospital stay and compared with the control group. The predictive accuracy of each marker was measured by area under the receiver operating curve. RESULTS: Forty healthy controls and 102 patients were enrolled in to the study. Twenty seven (26.5 %) patients had mild, 55 (53.9 %) - moderate and 20 (19.6 %) - severe AP. Only resistin (cut-off value 13.7 ng/ml) and IL-6 (cut-off value 473.4 pg/ml) were reliable early markers of SAP. IL-6 with cut-off value of 157.0 pg/ml was a predictor of necrosis. The peripancreatic necrosis volume of 112.5 ml was a marker of SAP and 433.0 ml cut off value could be used to predict the need of interventions. CONCLUSIONS: The prognostic value of adipokines in AP is limited. Only admission resistin levels could serve as an early predictor for SAP. The Lithuanian Regional Ethics Committee approved the study protocol (permission No. L-12-02/1/2/3/4) and all the patients and the control group provided written informed consent. PMID- 27549126 TI - Probing the functional impact of sub-retinal prosthesis. AB - Retinal prostheses are promising tools for recovering visual functions in blind patients but, unfortunately, with still poor gains in visual acuity. Improving their resolution is thus a key challenge that warrants understanding its origin through appropriate animal models. Here, we provide a systematic comparison between visual and prosthetic activations of the rat primary visual cortex (V1). We established a precise V1 mapping as a functional benchmark to demonstrate that sub-retinal implants activate V1 at the appropriate position, scalable to a wide range of visual luminance, but with an aspect-ratio and an extent much larger than expected. Such distorted activation profile can be accounted for by the existence of two sources of diffusion, passive diffusion and activation of ganglion cells' axons en passant. Reverse-engineered electrical pulses based on impedance spectroscopy is the only solution we tested that decreases the extent and aspect-ratio, providing a promising solution for clinical applications. PMID- 27549127 TI - A new motor synergy that serves the needs of oculomotor and eye lid systems while keeping the downtime of vision minimal. AB - The purpose of blinks is to keep the eyes hydrated and to protect them. Blinks are rarely noticed by the subject as blink-induced alterations of visual input are blanked out without jeopardizing the perception of visual continuity, features blinks share with saccades. Although not perceived, the blink-induced disconnection from the visual environment leads to a loss of information. Therefore there is critical need to minimize it. Here we demonstrate evidence for a new type of eye movement serving a distinct oculomotor demand, namely the resetting of eye torsion, likewise inevitably causing a loss of visual information. By integrating this eye movement into blinks, the inevitable down times of vision associated with each of the two behaviors are synchronized and the overall downtime minimized. PMID- 27549128 TI - An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican family. AB - BACKGROUND: Niemann-Pick disease type C (NP-C) is a fatal lysosomal neurodegenerative and neurovisceral disease. It is caused by defects in intracellular lipid trafficking, which lead to the accumulation of lipids and glycosphingolipids within the endosomes and lysosomes of affected individuals. Pathogenic variants of the NPC1 or NPC2 genes yield highly variable phenotypes with a time course that ranges from fetal onset (i.e., hydrops fetalis) to progressive dementia in adults. NP-C is typically inherited in an autosomal recessive manner. To our knowledge, no previous report has identified germline mosaicism as an inheritance mechanism in NP-C. CASE PRESENTATION: We report the case of a male Mexican patient with "variant" filipin staining and a juvenile form of NP-C attributed to compound heterozygosity for two previously reported pathogenic variants of NPC1: c.[1042C>T];[2780C>T] or p.[Arg348*];[Ala927Val]. The proband's mother and healthy sister were heterozygous carriers of the c.2780C > T (exon 18) and c.1042C > T (exon 8) variants, respectively. However, direct sequencing of exons 8 and 18 of NPC1 revealed no mutation in genomic DNA obtained from the father's peripheral blood. DNA profiling ruled out the possibility of non-paternity. We were unable to obtain a sperm sample to demonstrate paternal gonadal mosaicism. NPC1 haplotype analysis using 20 linked single nucleotide variants failed to yield sufficient information to document a p.(Arg348*) NPC1 pathogenic variant-associated haplotype in the family. CONCLUSIONS: We propose that this case of NP-C involves paternal germline mosaicism. To the best of our knowledge, this has not previously been reported in NP-C. PMID- 27549129 TI - Analysis on the situation of subjective well-being and its influencing factors in patients with ankylosing spondylitis. AB - BACKGROUND: To examine the subjective well-being (SWB) in patients with ankylosing spondylitis (AS) compared with the healthy controls, and to explore the associations between SWB and demographic characteristics, disease-specific variables in AS patients. METHODS: SWB was assessed with General Well-Being Schedule (GWBS) in 200 AS patients and 210 healthy controls. Comparisons among subgroups were performed to investigate how certain aspects operate as favorable or adverse factors in influencing SWB in the patients with AS. RESULTS: Both men and women with AS reported significantly impaired SWB on all scales of the GWBS except for the Control (O) scale. The results revealed that better sleep, lower disease activity and more family care predicted higher SWB. In AS patients, positive attitude towards therapy prospect was significantly associated with higher SWB. Therapy prospect refers to the hope of patients about the disease treatment. CONCLUSIONS: Compared with general population, SWB might be affected by the onset of AS. There are significant associations between SWB and sleep quality, BASDAI, APGAR, therapy prospect. PMID- 27549130 TI - Visualizing complex processes using a cognitive-mapping tool to support the learning of clinical reasoning. AB - BACKGROUND: Practical experience with clinical cases has played an important role in supporting the learning of clinical reasoning. However, learning through practical experience involves complex processes difficult to be captured by students. This study aimed to examine the effects of a computer-based cognitive mapping approach that helps students to externalize the reasoning process and the knowledge underlying the reasoning process when they work with clinical cases. A comparison between the cognitive-mapping approach and the verbal-text approach was made by analyzing their effects on learning outcomes. METHODS: Fifty-two third-year or higher students from two medical schools participated in the study. Students in the experimental group used the computer-base cognitive-mapping approach, while the control group used the verbal-text approach, to make sense of their thinking and actions when they worked with four simulated cases over 4 weeks. For each case, students in both groups reported their reasoning process (involving data capture, hypotheses formulation, and reasoning with justifications) and the underlying knowledge (involving identified concepts and the relationships between the concepts) using the given approach. RESULTS: The learning products (cognitive maps or verbal text) revealed that students in the cognitive-mapping group outperformed those in the verbal-text group in the reasoning process, but not in making sense of the knowledge underlying the reasoning process. No significant differences were found in a knowledge posttest between the two groups. CONCLUSIONS: The computer-based cognitive-mapping approach has shown a promising advantage over the verbal-text approach in improving students' reasoning performance. Further studies are needed to examine the effects of the cognitive-mapping approach in improving the construction of subject-matter knowledge on the basis of practical experience. PMID- 27549131 TI - Fractalkine shedding is mediated by p38 and the ADAM10 protease under pro inflammatory conditions in human astrocytes. AB - BACKGROUND: The fractalkine (CX3CR1) ligand is expressed in astrocytes and reported to be neuroprotective. When cleaved from the membrane, soluble fractalkine (sCX3CL1) activates the receptor CX3CR1. Although somewhat controversial, CX3CR1 is reported to be expressed in neurons and microglia. The membrane-bound form of CX3CL1 additionally acts as an adhesion molecule for microglia and infiltrating white blood cells. Much research has been done on the role of fractalkine in neuronal cells; however, little is known about the regulation of the CX3CL1 ligand in astrocytes. METHODS: The mechanisms involved in the up-regulation and cleavage of CX3CL1 from human astrocytes were investigated using immunocytochemistry, Q-PCR and ELISA. All statistical analysis was performed using GraphPad Prism 5. RESULTS: A combination of ADAM17 (TACE) and ADAM10 protease inhibitors was found to attenuate IL-1beta-, TNF-alpha- and IFN gamma-induced sCX3CL1 levels in astrocytes. A specific ADAM10 (but not ADAM17) inhibitor also attenuated these effects, suggesting ADAM10 proteases induce release of sCX3CL1 from stimulated human astrocytes. A p38 MAPK inhibitor also attenuated the levels of sCX3CL1 upon treatment with IL-1beta, TNF-alpha or IFN gamma. In addition, an IKKbeta inhibitor significantly reduced the levels of sCX3CL1 induced by IL-1beta or TNF-alpha in a concentration-dependent manner, suggesting a role for the NF-kB pathway. CONCLUSIONS: In conclusion, this study shows that the release of soluble astrocytic fractalkine is regulated by ADAM10 proteases with p38 MAPK also playing a role in the fractalkine shedding event. These findings are important for understanding the role of CX3CL1 in healthy and stimulated astrocytes and may benefit our understanding of this pathway in neuro inflammatory and neurodegenerative diseases. PMID- 27549132 TI - Variations in the metabolome in response to disease activity of rheumatoid arthritis. AB - BACKGROUND: Anti-Tumor Necrosis Factor (TNF) therapies are able to control rheumatoid arthritis (RA) disease activity and limit structural damage. Yet no predictive factor of response to anti-TNF has been identified. Metabolomic profile is known to vary in response to different inflammatory rheumatisms so determining it could substantially improve diagnosis and, consequently, prognosis. The aim of this study was to use mass spectrometry to determine whether there is variation in the metabolome in patients treated with anti-TNF and whether any particular metabolomic profile can serve as a predictor of therapeutic response. METHODS: Blood samples were analyzed in 140 patients with active RA before initiation of anti-TNF treatment and after 6 months of Anti-TNF treatment (100 good responders and 40 non-responders). Plasma was deproteinized, extracted and analyzed by reverse-phase chromatography-QToF mass spectrometry. Extracted and normalized ions were tested by univariate and ANOVA analysis followed by partial least-squares regression-discriminant analysis (PLS-DA). Orthogonal Signal Correction (OSC) was also used to filter data from unwanted non related effects. Disease activity scores (DAS 28) obtained at 6 months were correlated with metabolome variation findings to identify a metabolite that is predictive of therapeutic response to anti-TNF. RESULTS: After 6 months of anti TNF therapy, 100 patients rated as good responders and 40 patients as non responders according to EULAR criteria. Metabolomic investigations suggested two different metabolic fingerprints splitting the good-responders group and the non responders group, without differences in anti-TNF therapies. Univariate analysis revealed 24 significant ions in positive mode (p < 0.05) and 31 significant ions in negative mode (p < 0.05). Once intersected with PLS results, only 35 ions remained. Carbohydrate derivates emerged as strong candidate determinants of therapeutic response. CONCLUSIONS: This is the first study describing metabolic profiling in response to anti-TNF treatments using plasma samples. The study highlighted two different metabolic profiles splitting good responders from non responders. PMID- 27549133 TI - Deliberate or unintended: Intentions modulate empathic responses to others' economic payoffs in social interactions. AB - Previous studies examining empathy have revealed the neural substrates of how the physical pain of others is represented in the human brain. However, little is known about the empathic modulation of behavioral and neural responses to others' economic payoffs, especially in the social context. In the present study, we engaged participants in a revised Dictator Game as observers who observe the powerless players receiving varied offers proposed by the dominant players, establishing the link between empathy and fairness perception. Results showed that unfair division schemes elicited a more pronounced FRN than fair ones only if a human agent proposed the initial offer. In addition, observers sacrificed their own payments to adjust unfair proposals, especially when a human agent proposed the offer. Thus, results of the current study demonstrated that perceived intention modulates behavioral and neural responses to others' economic payoffs in social interactions. PMID- 27549134 TI - Retrofit Weight-Loss Outcomes at 6, 12, and 24 Months and Characteristics of 12 Month High Performers: A Retrospective Analysis. AB - BACKGROUND: Obesity is the leading cause of preventable death costing the health care system billions of dollars. Combining self-monitoring technology with personalized behavior change strategies results in clinically significant weight loss. However, there is a lack of real-world outcomes in commercial weight-loss program research. OBJECTIVE: Retrofit is a personalized weight management and disease-prevention solution. This study aimed to report Retrofit's weight-loss outcomes at 6, 12, and 24 months and characterize behaviors, age, and sex of high performing participants who achieved weight loss of 10% or greater at 12 months. METHODS: A retrospective analysis was performed from 2011 to 2014 using 2720 participants enrolled in a Retrofit weight-loss program. Participants had a starting body mass index (BMI) of >25 kg/m2 and were at least 18 years of age. Weight measurements were assessed at 6, 12, and 24 months in the program to evaluate change in body weight, BMI, and percentage of participants who achieved 5% or greater weight loss. A secondary analysis characterized high-performing participants who lost >=10% of their starting weight (n=238). Characterized behaviors were evaluated, including self-monitoring through weigh-ins, number of days wearing an activity tracker, daily step count average, and engagement through coaching conversations via Web-based messages, and number of coaching sessions attended. RESULTS: Average weight loss at 6 months was -5.55% for male and -4.86% for female participants. Male and female participants had an average weight loss of -6.28% and -5.37% at 12 months, respectively. Average weight loss at 24 months was -5.03% and -3.15% for males and females, respectively. Behaviors of high-performing participants were assessed at 12 months. Number of weigh-ins were greater in high-performing male (197.3 times vs 165.4 times, P=.001) and female participants (222 times vs 167 times, P<.001) compared with remaining participants. Total activity tracker days and average steps per day were greater in high-performing females (304.7 vs 266.6 days, P<.001; 8380.9 vs 7059.7 steps, P<.001, respectively) and males (297.1 vs 255.3 days, P<.001; 9099.3 vs 8251.4 steps, P=.008, respectively). High-performing female participants had significantly more coaching conversations via Web-based messages than remaining female participants (341.4 vs 301.1, P=.03), as well as more days with at least one such electronic message (118 vs 108 days, P=.03). High-performing male participants displayed similar behavior. CONCLUSIONS: Participants on the Retrofit program lost an average of -5.21% at 6 months, -5.83% at 12 months, and 4.09% at 24 months. High-performing participants show greater adherence to self monitoring behaviors of weighing in, number of days wearing an activity tracker, and average number of steps per day. Female high performers have higher coaching engagement through conversation days and total number of coaching conversations. PMID- 27549135 TI - Smoking on the margins: a comprehensive analysis of a municipal outdoor smoke free policy. AB - BACKGROUND: This study examined the formulation, adoption, and implementation of a ban on smoking in the parks and beaches in Vancouver, Canada. METHODS: Informed by Critical Multiplism, we explored the policy adoption process, support for and compliance with a local bylaw prohibiting smoking in parks and on beaches, experiences with enforcement, and potential health equity issues through a series of qualitative and quantitative studies. RESULTS: Findings suggest that there was unanimous support for the introduction of the bylaw among policy makers, as well as a high degree of positive public support. We observed that smoking initially declined following the ban's implementation, but that smoking practices vary in parks by location. We also found evidence of different levels of enforcement and compliance between settings, and between different populations of park and beach users. CONCLUSIONS: Overall success with the implementation of the bylaw is tempered by potential increases in health inequities because of variable enforcement of the ban; greatest levels of smoking appear to continue to occur in the least advantaged areas of the city. Jurisdictions developing such policies need to consider how to allocate sufficient resources to enhance voluntary compliance and ensure that such bylaws do not contribute to health inequities. PMID- 27549136 TI - A simplified approach to haemoptysis. AB - Haemoptysis is commonly seen in the healthcare setting. It can lead to life threatening complications and therefore requires careful evaluation of the severity and status of the patient. Common causes of haemoptysis can be broadly grouped into five main categories: infective, neoplastic, vascular, autoimmune and drug-related. Detailed history-taking and careful physical examination are necessary to provide a diagnosis and assess the patient's haemodynamic status. Physicians must have a clear understanding of the criteria for further investigations and the need for a specialist or inpatient referral for management. PMID- 27549137 TI - DNA barcoding and surveillance sampling strategies for Culicoides biting midges (Diptera: Ceratopogonidae) in southern India. AB - BACKGROUND: Culicoides spp. biting midges transmit bluetongue virus (BTV), the aetiological agent of bluetongue (BT), an economically important disease of ruminants. In southern India, hyperendemic outbreaks of BT exert high cost to subsistence farmers in the region, impacting on sheep production. Effective Culicoides spp. monitoring methods coupled with accurate species identification can accelerate responses for minimising BT outbreaks. Here, we assessed the utility of sampling methods and DNA barcoding for detection and identification of Culicoides spp. in southern India, in order to provide an informed basis for future monitoring of their populations in the region. METHODS: Culicoides spp. collected from Tamil Nadu and Karnataka were used to construct a framework for future morphological identification in surveillance, based on sequence comparison of the DNA barcode region of the mitochondrial cytochrome c oxidase I (COI) gene and achieving quality standards defined by the Barcode of Life initiative. Pairwise catches of Culicoides spp. were compared in diversity and abundance between green (570 nm) and ultraviolet (UV) (390 nm) light emitting diode (LED) suction traps at a single site in Chennai, Tamil Nadu over 20 nights of sampling in November 2013. RESULTS: DNA barcode sequences of Culicoides spp. were mostly congruent both with existing DNA barcode data from other countries and with morphological identification of major vector species. However, sequence differences symptomatic of cryptic species diversity were present in some groups which require further investigation. While the diversity of species collected by the UV LED Center for Disease Control (CDC) trap did not significantly vary from that collected by the green LED CDC trap, the UV CDC significantly outperformed the green LED CDC trap with regard to the number of Culicoides individuals collected. CONCLUSIONS: Morphological identification of the majority of potential vector species of Culicoides spp. samples within southern India appears relatively robust; however, potential cryptic species diversity was present in some groups requiring further investigation. The UV LED CDC trap is recommended for surveillance of Culicoides in southern India. PMID- 27549139 TI - Episomal Lentiviral Vector-Mediated miR-145 Overexpression Inhibits Proliferation and Induces Apoptosis of Human Esophageal Carcinomas Cells. AB - BACKGROUND: Gene therapy is a promising approach for the treatment of various cancers. However, most viral vectors used for this purpose carry risks, including potential integration into the host genome. OBJECTIVE: We addressed this issue in the present study by constructing an episomal lentiviral vector using the . interferon matrix attachment region to express the microRNA -145(miR-145), and examining the effect of miR-145 overexpression on human esophageal carcinomas (EC) cells. Some recent relevant patents are also discussed. METHOD: Expression levels of miR-145 and the marker protein enhanced green fluorescent protein (EGFP) in infected ECA109 and EC9706 human esophageal carcinoma cells were detected by quantitative PCR and flow cytometry, respectively. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 and flow cytometry, respectively. Plasmid rescue experiments and fluorescence in situ hybridization were used to determine the episomal status of the transfected vector. RESULTS: We found that EGFP and miR-145 were highly expressed in EC cells, and miR-145 overexpression inhibited cell proliferation and induced apoptosis. Moreover, the lentiviral vector did not integrate into the host genome, but was maintained episomally at lower copy numbers. CONCLUSION: Taken together, our results demonstrate that miR-145-expressing episomal lentiviral vectors are a promising tool for gene therapy in the treatment of EC. PMID- 27549138 TI - The influence of weight and gender on intestinal bacterial community of wild largemouth bronze gudgeon (Coreius guichenoti, 1874). AB - BACKGROUND: Largemouth bronze gudgeon (Coreius guichenoti) is of economic importance in China, distributed in upstream regions of the Yangtze River in China. But it has recently dramatically declined and is close to elimination. However, there is little knowing about the character of its intestinal microbiota. This study was conducted to elucidate the intestinal microbiota of wild largemouth bronze gudgeon with different body weight and gender. RESULTS: Thirty wild largemouth bronze gudgeon were measured for body length and body weight, and identified for male and female according to gonadal development, and thereafter the intestinal microbiota's were assessed by MiSeq sequencing of 16S rRNA genes. The results revealed that phyla Proteobacteria and Tenericutes were dominant in wild largemouth bronze gudgeon intestine independent of the body weight. Shannon's and Inverse Simpson's diversity indexes were significant (P < 0.05) different between male and female fish. The phylum profile in the intestine of male fish revealed that phylum Proteobacteria was dominant, in contrast to female fish where five phyla Tenericutes, Proteobacteria, Firmicutes, Fusobacteria and Spirochaetes were dominant. The genus profile revealed that genera Shewanella and Unclassified bacteria were dominant in male fish, while genus Mycoplasma was dominant in female fish. CONCLUSIONS: Our results revealed that the intestinal microbial community of wild largemouth bronze gudgeon was dominated by the phyla Proteobacteria and Tenericutes regardless of the different body weight, but the communities are significant different between male and female fish. These results provide a theoretical basis to understand the biological mechanisms relevant to the protection of the endangered fish species. PMID- 27549140 TI - A novel multiplex assay for simultaneous quantification of total and S129 phosphorylated human alpha-synuclein. AB - BACKGROUND: Alpha-synuclein (asyn) has been shown to play an important role in the neuropathology of Parkinson's disease (PD). In the diseased brain, classic intraneuronal inclusions called Lewy bodies contain abnormal formations of asyn protein which is mostly phosphorylated at serine 129 (pS129 asyn). This suggests that post-translational modifications may play a role in the pathogenic process. To date, several uniplex assays have been developed in order to quantify asyn not only in the brain but also in cerebrospinal fluid and blood samples in order to correlate asyn levels to disease severity and progression. Notably, only four assays have been established to measure pS129 asyn specifically and none provide simultaneous readout of the total and pS129 species. Therefore, we developed a sensitive high-throughput duplex assay quantifying total and pS129 human asyn (h asyn) in the same well hence improving accuracy as well as saving time, consumables and samples. RESULTS: Using our newly established duplex assay we measured total and pS129 h-asyn in vitro showing that polo-like kinase 2 (PLK2) can phosphorylate asyn up to 41 % in HEK293 cells and in vivo the same kinase phosphorylated h-asyn up to 17 % in rat ventral midbrain neurons. Interestingly, no increase in phosphorylation was observed when PLK2 and h-asyn were co expressed in rat striatal neurons. Furthermore, using this assay we investigated h-asyn levels in brain tissue samples from patients with PD as well as PD dementia and found significant differences in pS129 h-asyn levels not only between disease tissue and healthy control samples but also between the two distinct disease states especially in hippocampal tissue samples. CONCLUSIONS: These results demonstrate that our duplex assay for simultaneous quantification is a useful tool to study h-asyn phosphorylation events in biospecimens and will be helpful in studies investigating the precise causative link between post translational modification of h-asyn and PD pathology. PMID- 27549142 TI - Fetal macrosomia as a risk factor for shoulder dystocia during vacuum extraction. AB - OBJECTIVE: Vacuum extraction of a macrosomic fetus is considered a risk factor for shoulder dystocia (SD). We evaluated maternal and fetal outcomes following vacuum extraction of macrosomic infants. METHODS: A retrospective cohort study conducted in two large teaching hospitals. All deliveries of macrosomic infants by vacuum extraction and vaginal delivery were compared. The primary outcome measure was SD. Secondary outcome measures were severe perineal lacerations and postpartum hemorrhage. For statistical analysis, we used McNemar's test and chi2 or Fisher's exact tests. Odds ratios were analyzed via a logistic regression model. RESULTS: From 2003 to 2013, there were 6019 (5.45%) deliveries of macrosomic fetuses, and 230 (0.21%) were delivered by vacuum extraction. There were 23 (10%) and seven (3.04%) cases of SD in the study and control groups, respectively. The risk of SD was significantly higher in the study group (p > 0.05). We found a significant association between SD and vacuum delivery [p = 0.003; OR = 3.54 (95% CI: 1.49-8.42)]. The composite adverse neonatal outcome rate was 6.5% (15/230) and 1.7% (4/230) in the study and control groups, respectively (p = 0.009). CONCLUSION: Vacuum extraction of a macrosomic infant is a risk factor for shoulder dystocia but not for postpartum hemorrhage or severe vaginal tears. PMID- 27549141 TI - Identification of bacterial contaminants in polyherbal medicines used for the treatment of tuberculosis in Amatole District of the Eastern Cape Province, South Africa, using rapid 16S rRNA technique. AB - BACKGROUND: Polyherbal medicines are used for the treatment of many diseases in many African and Asian communities. With the increasing use of these remedies, several investigations have shown that they are associated with a broad variety of residues and contaminants. This study investigates the presence of bacteria in the polyherbal medicines used for the treatment of tuberculosis (TB) in the Eastern Cape Province of South Africa. METHODS: Bacterial DNA was extracted from the polyherbal medicines, and a fragment of the bacterial 16S rRNA gene was amplified by PCR with universal primers 27F and 518R. The amplicons were visualised on agarose gel electrophoresis, followed by end repair and adaptor ligation. They were further purified and quantified using Library Preparation kit NEBNext(r) UltraT DNA Library Prep Kit for Illumina, and the amplicons were run on illumina's MiSeq platform. RESULTS: Different bacterial species were identified in all each of the polyherbal medicines. Generally, the most prominent and common bacteria recovered from all the samples were Bacillus sp., Enterobacter sp., Klebsiella sp., Rahnella sp., Paenibacillus sp., Clostridium sp. and Pantoea sp. Others are Pseudomonas sp., Raoultella ornithinolytica, Salmonella enterica and Eubacterium moniliforme. CONCLUSIONS: This study, thus, revealed the presence of pathogenic and non-pathogenic bacteria in the polyherbal medicines used for the treatment of tuberculosis in the study area. The implications of the findings are discussed in relation to the health care of the patients of tuberculosis in the study area, having in mind that they are immunocompromised individuals. PMID- 27549143 TI - Design, Synthesis and Evaluation of the Antidepressant and Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles. AB - BACKGROUND: Epilepsy and depression are two of the common diseases seriously threatening life and health of human. A shared neurobiological substrate led to the bidirectional relationship and high comorbid occurrence of the two disorders. Recently, an increasing number of patients with epilepsy (PWE) require some form of antidepressant medication. However, most of the available antidepressants are inadequate for PWE for some reasons. So, the search for novel and increasingly effective drugs with anticonvulsant and antidepressant activities is necessary. METHODS: A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles (5a p) were designed and synthesized. Their anticonvulsant activities were evaluated using maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. Their antidepressant activities were screened with the forced swimming test (FST). RESULTS: All the compounds showed anti-MES activities in different degree, among which 5g and 5j were the most promising one with ED50 value of 31.7 and 12.7 mg/kg, respectively. What's more, 5g and 5j also exhibited nice anti-scPTZ activities and low neurotoxicity. Interestingly, these compounds also showed good antidepressant activities in FST. And the efficacy of 5g were also confirmed by a tail suspension test and a open field test. The pretreatment of thiosemicarbazide (an inhibitor of gamma- aminobutyric acid synthesis enzyme) significantly increased the ED50 of 5g in MES and reversed the reductions in the immobility time of 5g in FST. CONCLUSION: Triazole-containing benzo[d]oxazole is a good skeleton to develop compounds with both anticonvulsant and antidepressant activities. We have got the compound 5g, which display remarkable antidepressant and anticonvulsant activities, and the GABAergic system was involved in the action mechanism of 5g. PMID- 27549144 TI - Role of KCa3.1 Channels in CNS Diseases: A Concise Review. AB - KCa3.1 protein is part of a heterotetrameric voltage-independent potassium channel, the activity of which depends on the intracellular calcium binding to calmodulin. KCa3.1 is immensely significant in regulating immune responses and primarily expressed in cells of hematopoietic lineage. It is one of the attractive pharmacological targets that are known to inhibit neuroinflammation. KCa3.1 blockers mediate neuroprotection through multiple mechanisms, such as by targeting microglia-mediated neuronal killing. KCa3.1 modulators may provide alternative treatment options for neurological disorders like ischemic stroke, Alzheimer disease, glioblastoma multiforme, multiple sclerosis and spinal cord injury. This review is an attempt to draw attention towards KCa3.1 channel, which was never exploited to its full potential as a viable therapeutic candidate against various neurological disorders. PMID- 27549145 TI - Effectiveness of a tailored return to work program for cancer survivors with job loss: results of a randomized controlled trial. AB - BACKGROUND: Up to 53% of cancer survivors (CSs) experiences job loss during or after treatment. To support CSs with job loss in the Netherlands, a tailored return to work (RTW) program was developed. The objective of this study was to assess the effectiveness of the program on duration until sustainable RTW in CSs with job loss. MATERIAL AND METHODS: This study employed a two-armed (intervention/control) randomized controlled design with one-year follow-up. The primary outcome measure was duration until sustainable RTW. The secondary outcome measures were: rate of RTW, fatigue, quality of life, and participation in society. Descriptive analyses, Kaplan-Meier estimators and Cox regression analyses were conducted. RESULTS: Participants (N = 171) had a mean age of 48.4 years (SD = 8.6). The majority was female (69%) and breast cancer survivor (40%). The crude hazard ratio (HR) for duration until sustainable RTW was 0.86 (95% CI 0.46-1.62; p = 0.642). In the adjusted model, the intervention group had a slight, but statistically non-significant, improvement in duration until sustainable RTW compared to the control group (HR 1.16; 95% CI 0.59-2.31; p = 0.663). The program did not have any significant effects on secondary outcome measures. CONCLUSION: As the tailored RTW program did not demonstrate a statistically significant effect on duration until sustainable RTW in CSs with job loss, implementation of the program in its current form is not recommended. PMID- 27549146 TI - Super-resolution imaging for monitoring cytoskeleton dynamics. AB - The cytoskeleton is a key cellular structure that is important in the control of cellular movement, structure, and sensing. To successfully image the individual cytoskeleton components, high resolution and super-resolution fluorescence imaging methods are needed. This review covers the three basic cytoskeletal elements and the relative benefits and drawbacks of fixed versus live cell imaging before moving on to recent studies using high resolution and super resolution techniques. The techniques covered include the near-diffraction limited imaging methods of confocal microscopy and TIRF microscopy and the super resolution fluorescence imaging methods of STORM, PALM, and STED. PMID- 27549147 TI - Non-convulsive status epilepticus in a patient with carbon-monoxide poisoning treated with hyperbaric oxygen therapy. AB - The presentation of carbon monoxide poisoning is non-specific and highly variable. Hyperbaric oxygen therapy is used for the treatment of this condition. Various reports show the occurrence of self-limiting seizures after carbon monoxide poisoning and as a consequence of hyperbaric oxygen therapy. Contrary to the seizures, status epilepticus has been rarely observed in these conditions. The exact pathophysiology underlying seizures and status epilepticus associated with carbon monoxide poisoning and hyperbaric oxygen therapy is not really clear, and some elements appear to be common to both conditions. We describe a case of non-convulsive status epilepticus in a patient with carbon monoxide poisoning treated with hyperbaric oxygen therapy. The mechanism, MRI findings and implications are discussed. PMID- 27549148 TI - Fetal development of the corpus callosum: Insights from a 3T DTI and tractography study in a patient with segmental callosal agenesis. AB - Commissural embryology mechanisms are not yet completely understood. The study and comprehension of callosal dysgenesis can provide remarkable insights into embryonic or fetal commissural development. The diffusion tensor imaging (DTI) technique allows the in vivo analyses of the white-matter microstructure and is a valid tool to clarify the disturbances of brain connections in patients with dysgenesis of the corpus callosum (CC). The segmental callosal agenesis (SCAG) is a rare partial agenesis of the corpus callosum (ACC). In a newborn with SCAG the DTI and tractography analyses proved that the CC was made of two separate segments consisting respectively of the ventral part in the genu and body of the CC, connecting the frontal lobes, and the dorsal part in the CC splenium and the attached hippocampal commissure (HC), connecting the parietal lobes and the fornix. These findings support the embryological thesis of a separated origin of the ventral and the dorsal parts of the CC. PMID- 27549150 TI - Accuracy of SWI sequences compared to T2*-weighted gradient echo sequences in the detection of cerebral cavernous malformations in the familial form. AB - PURPOSE: The purpose of this study was to assess the accuracy of susceptibility weighted imaging (SWI), compared with T2*-weighted gradient echo (GRE) imaging in assessing cerebral cavernous malformations. MATERIALS AND METHODS: We retrospectively evaluated 21 patients with a familial form of cavernous malformation. Magnetic resonance (MR) protocol included non-enhanced and contrast enhanced fast-spin echo (FSE) T1-weighted sequences, FSE T2-weighted sequences, fluid-attenuated inversion-recovery (FLAIR), GRE T2*-weighted and SWI sequences. Images were reviewed in consensus by two expert neuroradiologists to assess the location, number, size and conspicuity of the lesions on T2*-weighted GRE and SWI sequences. Statistical differences in the number, size and conspicuity of the lesions seen on the SWI images and the T2*-weighted GRE images were assessed with the nonparametric Wilcoxon signed rank test. RESULTS: The number of cavernous malformations was significantly higher (p < .001) on the SWI images (n = 152) than on T2*-weighted GRE images (n = 56). Lesion size was significantly higher (p < .001) on SWI images (mean: 0.4 cm, SD +/- 0.55) than on T2*-weighted GRE sequences (mean: 0.2 cm, SD +/- 0.51) and the differences were statistically significant (p < .001). Lesion conspicuity was significant higher (p < .001) on SWI than on T2*-weighted GRE images. In one patient who underwent a 2-month follow-up for the onset of neurologic symptoms related to cerebral hemorrhage, a cerebral hematoma was identified at the site of a cerebral cavernous malformation that was demonstrated only on the SWI images in the previous MR examination. CONCLUSIONS: The SWI sequence, being more sensitive to substances which distort the local magnetic field than the GRE T2*W sequence, showed a higher sensitivity in identifying cerebral cavernous malformations. Thus, routine clinical neuroimaging protocol should contain SWI sequences to evaluate patients with (or suspected) cerebral cavernous malformations. PMID- 27549151 TI - Brain MRI findings in two Turkish pediatric patients with aspartylglucosaminuria. AB - Aspartylglucosaminuria is a rare lysosomal storage disorder that occurs as a result of a deficiency of the aspartylglucosaminidase enzyme. Because the disease is commonly referred to as the Finnish disease heritage, it is underdiagnosed outside of Finland. To date, only three Turkish patients are described in the literature. Here we describe the clinical and brain magnetic resonance imaging findings in two Turkish cousins with aspartylglucosaminuria, which can raise the suspicion of this rare disease in clinical practice. PMID- 27549149 TI - Post-ischaemic hyperperfusion in traumatic middle cerebral artery dissection detected by arterial spin labelling of magnetic resonance imaging. AB - We report a patient with a traumatic middle cerebral artery dissection, which showed hyperperfusion in the territory supplied by the left middle cerebral artery. A 45-year-old man experienced speech disturbance and motor weakness in his right hemibody on the day following mild head trauma. His symptoms worsened on the fourth day. Magnetic resonance imaging showed narrowing in the left M1 portion of the middle cerebral artery. Angiography showed narrowing and dilatation in the left middle cerebral artery trunk. The lesion was diagnosed as a dissection of the middle cerebral artery. Arterial spin labelling of magnetic resonance imaging and single photon emission computed tomography showed increased cerebral blood flow in the left temporal region compared with the right. The patient was treated conservatively and the symptoms gradually improved. The hyperperfusion observed on arterial spin labelling and single photon emission computed tomography gradually improved and disappeared on the 25th day. This is the first reported case of traumatic middle cerebral artery dissection, which showed post-ischaemic hyperperfusion in the territory of the affected artery. To detect hyperperfusion in the brain, arterial spin labelling is a useful technique. PMID- 27549152 TI - Dural arteriovenous fistula of the craniocervical junction manifesting as cerebellar haemorrhage. AB - We report a rare case of dural arteriovenous fistula at the craniocervical junction manifesting as cerebellar haemorrhage, which posed a diagnostic challenge for physicians. A 77-year-old woman with no history of arterial hypertension presented to our Emergency Department with dizziness, and imaging studies revealed a small cerebellar haemorrhage. She was diagnosed with hypertensive intracerebral haemorrhage and conservatively treated. Four months later, she developed subarachnoid haemorrhage, and imaging studies revealed dural arteriovenous fistula at the left C1 dural sleeve. Disruption of a distended cerebellar vein due to venous hypertension by dural arteriovenous fistula was considered to be responsible for intracerebral haemorrhage and subarachnoid haemorrhage. Dural arteriovenous fistula was cured following surgical ligation of a feeding artery and a draining vein. The present case was educational in that effort to identify the cause of bleeding using vascular imaging studies may be important in patients with seemingly typical hypertensive intracerebral haemorrhage, particularly in those without a past history of arterial hypertension. PMID- 27549153 TI - Prevalence of hepatitis B and clinical outcomes in inflammatory bowel disease patients in a viral-endemic region. AB - BACKGROUND: Little is known of the prevalence of hepatitis B virus (HBV) infection and its effect on choice of therapy and disease course in patients with inflammatory bowel disease (IBD). We assessed the prevalence of HBV in Hong Kong as well as determinants of altered transaminases, effects of HBV infection on therapeutic strategy and clinical course in IBD. METHODS: In this retrospective cohort, hepatitis B surface antigen (HBsAg), liver function tests, and IBD disease characteristics were recorded. Logistic regression was used to identify factors associated with altered transaminases. RESULTS: Four hundred six IBD patients were recruited. HBV infection was found in 5.7 % patients in Hong Kong. The use of steroids (OR, 2.52; p = 0.010) and a previous history of surgery (OR 2.33; p = 0.026) were associated with altered transaminases in IBD. There was no significant difference in disease control and use of IBD medication between HBsAg positive and HBsAg-negative IBD patients. CONCLUSION: The prevalence of HBV among patients with IBD in Hong Kong (5.7 %) is similar to that of general population (~7 %). There was no difference in disease control and use of IBD medication between subjects with or without HBV. PMID- 27549154 TI - Tailored parameter optimization methods for ordinary differential equation models with steady-state constraints. AB - BACKGROUND: Ordinary differential equation (ODE) models are widely used to describe (bio-)chemical and biological processes. To enhance the predictive power of these models, their unknown parameters are estimated from experimental data. These experimental data are mostly collected in perturbation experiments, in which the processes are pushed out of steady state by applying a stimulus. The information that the initial condition is a steady state of the unperturbed process provides valuable information, as it restricts the dynamics of the process and thereby the parameters. However, implementing steady-state constraints in the optimization often results in convergence problems. RESULTS: In this manuscript, we propose two new methods for solving optimization problems with steady-state constraints. The first method exploits ideas from optimization algorithms on manifolds and introduces a retraction operator, essentially reducing the dimension of the optimization problem. The second method is based on the continuous analogue of the optimization problem. This continuous analogue is an ODE whose equilibrium points are the optima of the constrained optimization problem. This equivalence enables the use of adaptive numerical methods for solving optimization problems with steady-state constraints. Both methods are tailored to the problem structure and exploit the local geometry of the steady state manifold and its stability properties. A parameterization of the steady state manifold is not required. The efficiency and reliability of the proposed methods is evaluated using one toy example and two applications. The first application example uses published data while the second uses a novel dataset for Raf/MEK/ERK signaling. The proposed methods demonstrated better convergence properties than state-of-the-art methods employed in systems and computational biology. Furthermore, the average computation time per converged start is significantly lower. In addition to the theoretical results, the analysis of the dataset for Raf/MEK/ERK signaling provides novel biological insights regarding the existence of feedback regulation. CONCLUSION: Many optimization problems considered in systems and computational biology are subject to steady-state constraints. While most optimization methods have convergence problems if these steady-state constraints are highly nonlinear, the methods presented recover the convergence properties of optimizers which can exploit an analytical expression for the parameter-dependent steady state. This renders them an excellent alternative to methods which are currently employed in systems and computational biology. PMID- 27549155 TI - The comparison of perioperative outcomes of robot-assisted and open partial nephrectomy: a systematic review and meta-analysis. AB - BACKGROUND: Robot-assisted partial nephrectomy (RAPN) has been widely used worldwide, to determine whether RAPN is a safe and effective alternative to open partial nephrectomy (OPN) via the comparison of RANP and OPN. METHODS: A comprehensive literature search was performed within the databases including PubMed, Cochrane Library, and Embase updated on 30 September 2015. Summary data with their corresponding 95 % confidence intervals (CIs) were calculated using a random effects or fixed effects model. Heterogeneity and publication bias were also evaluated. RESULTS: A total of 16 comparative studies including 3024 cases were used for this meta-analysis. There are no significant differences in the demographic characteristic between the two groups, but the age was lower and the tumor size was smaller for the RAPN group. RAPN had a longer operative time and warm ischemia time but which showed less estimated blood loss, hospital stay, and perioperative complications. No differences existed in the margin status, the change of glomerular filtration rate, transfusion rate, and conversion rate between the two groups. There was no significant publication bias. CONCLUSIONS: RAPN offered a lower rate of perioperative complications, less estimated blood loss, and shorter length of hospital stay than OPN, suggesting that RAPN can be an effective alternative to OPN. Well-designed prospective randomized controlled trials will be helpful in validating our findings. PMID- 27549156 TI - The influence of travel time on emergency obstetric care seeking behavior in the urban poor of Bangladesh: a GIS study. AB - BACKGROUND: Availability of Emergency Obstetric Care (EmOC) is crucial to avert maternal death due to life-threatening complications potentially arising during delivery. Research on the determinants of utilization of EmOC has neglected urban settings, where traffic congestion can pose a significant barrier to the access of EmOC facilities, particularly for the urban poor due to costly and limited transportation options. This study investigates the impact of travel time to EmOC facilities on the utilization of facility-based delivery services among mothers living in urban poor settlements in Sylhet, Bangladesh. METHODS: A cross sectional EmOC health-seeking behavior survey from 39 poor urban clusters was geo spatially linked to a comprehensive geo-referenced dataset of EmOC facility locations. Geo-spatial techniques and logistic regression were then applied to quantify the impact of travel time on place of delivery (EmOC facility or home), while controlling for confounding socio-cultural and economic factors. RESULTS: Increasing travel time to the nearest EmOC facility is found to act as a strong deterrent to seeking care for the urban poor in Sylhet. Logistic regression results indicate that a 5-min increase in travel time to the nearest EmOC facility is associated with a 30 % decrease (0.655 odds ratio, 95 % CI: 0.529 0.811) in the likelihood of delivery at an EmOC facility rather than at home. Moreover, the impact of travel time varies substantially between public, NGO and private facilities. A 5-min increase in travel time from a private EmOC facility is associated with a 32.9 % decrease in the likelihood of delivering at a private facility, while for public and Non-Government Organizations (NGO) EmOC facilities, the impact is lower (28.2 and 28.6 % decrease respectively). Other strong determinants of delivery at an EmOC facility are the use of antenatal care and mother's formal education, while Muslim mothers are found to be more likely to deliver at home. CONCLUSIONS: Geospatial evidence points to the need to strengthen referral and emergency transport systems in order to reduce urban travel time, and establish or relocate EmOC facilities closer to where the poor reside. However, female education and antenatal care coverage remain the most important determinants of facility delivery. PMID- 27549157 TI - External Comparison of Recent Predictive Nomograms for Stone-Free Rate Using Retrograde Flexible Ureteroscopy with Laser Lithotripsy. AB - OBJECTIVE: To assess and compare the applicability of the Resorlu-Unsal Stone Score (RUSS) and the Modified Seoul National University Renal Stone Complexity (S ReSC) score for flexible ureterorenoscopy (f-URS). PATIENTS AND METHODS: We retrospectively analyzed the hospital files of 719 patients who had been treated with f-URS for kidney stone at two referral centers between July 2012 and December 2015. The RUSS and Modified S-ReSC scores were calculated by the same surgeon for each patient by using imaging methods and were compared as to their predictive capability for postoperative success. RESULTS: A total of 339 patients (168 men and 171 women) with a mean age of 46.5 +/- 16.1 (range:1-86) years and a mean body mass index of 27.1 +/- 4.1 (range: 12.8-38.5) were included in the study. The mean stone size was 14.4 +/- 5.4 (4-40) mm, and the mean stone surface area was 145.3 +/- 76.8 (20-658) mm2. The overall stone-free rate was 70.1%. The mean scores were 0.5 +/- 0.7 and 1.8 +/- 1.1 for the RUSS and Modified S-ReSC, respectively. In the logistic regression analysis, musculoskeletal deformity, stone size, and the RUSS were identified as independent predictive factors affecting stone-free status (p: 0, p: 0.014, p: 0.048, respectively). Among these parameters, the RUSS had the highest predictive capability (area under curve value 0.65, [95% confidence interval 589, 721]). CONCLUSIONS: Stone size, presence of musculoskeletal abnormalities, and the RUSS score are important factors affecting SF status after f-URS. Despite the RUSS being an independent predictive factor for SF status, more comprehensive systems with higher predictive capability are needed for clinical usage and academic reporting. PMID- 27549158 TI - Pedagogical monitoring as a tool to reduce dropout in distance learning in family health. AB - BACKGROUND: This paper presents the results of a study of the Monsys monitoring system, an educational support tool designed to prevent and control the dropout rate in a distance learning course in family health. Developed by UNA-SUS/UFMA, Monsys was created to enable data mining in the virtual learning environment known as Moodle. METHODS: This is an exploratory study using documentary and bibliographic research and analysis of the Monsys database. Two classes (2010 and 2011) were selected as research subjects, one with Monsys intervention and the other without. The samples were matched (using a ration of 1:1) by gender, age, marital status, graduation year, previous graduation status, location and profession. Statistical analysis was performed using the chi-square test and a multivariate logistic regression model with a 5 % significance level. RESULTS: The findings show that the dropout rate in the class in which Monsys was not employed (2010) was 43.2 %. However, the dropout rate in the class of 2011, in which the tool was employed as a pedagogical team aid, was 30.6 %. After statistical adjustment, the Monsys monitoring system remained in correlation with the course completion variable (adjusted OR = 1.74, IC95% = 1.17-2.59; p = 0.005), suggesting that the use of the Monsys tool, isolated to the adjusted variables, can enhance the likelihood that students will complete the course. Using the chi-square test, a profile analysis of students revealed a higher completion rate among women (67.7 %) than men (52.2 %). Analysis of age demonstrated that students between 40 and 49 years dropped out the least (32.1 %) and, with regard to professional training, nurses have the lowest dropout rates (36.3 %). CONCLUSIONS: The use of Monsys significantly reduced the dropout, with results showing greater association between the variables denoting presence of the monitoring system and female gender. PMID- 27549159 TI - Clinics in diagnostic imaging (169). Intermuscular lipoma in the thenar eminence of the right hand. AB - A 54-year-old woman presented with a large mass on her right hand that was progressively enlarging over a period of a few years. She had cosmetic concerns about the enlarging mass and experienced interference with routine activity. Physical examination revealed a soft, mobile, non-tender, lobulated mass with well-defined margins. Magnetic resonance imaging showed the soft lump to be a lipomatous mass in the deep palmar space of the hand, which was subsequently surgically resected. The imaging features of deep palmar lipomas of the hand and other common benign lesions at this location are discussed. PMID- 27549160 TI - Comparing the MRI-based Goutallier Classification to an experimental quantitative MR spectroscopic fat measurement of the supraspinatus muscle. AB - BACKGROUND: The Goutallier Classification is a semi quantitative classification system to determine the amount of fatty degeneration in rotator cuff muscles. Although initially proposed for axial computer tomography scans it is currently applied to magnet-resonance-imaging-scans. The role for its clinical use is controversial, as the reliability of the classification has been shown to be inconsistent. The purpose of this study was to compare the semi quantitative MRI based Goutallier Classification applied by 5 different raters to experimental MR spectroscopic quantitative fat measurement in order to determine the correlation between this classification system and the true extent of fatty degeneration shown by spectroscopy. METHODS: MRI-scans of 42 patients with rotator cuff tears were examined by 5 shoulder surgeons and were graduated according to the MRI based Goutallier Classification proposed by Fuchs et al. Additionally the fat/water ratio was measured with MR spectroscopy using the experimental SPLASH technique. The semi quantitative grading according to the Goutallier Classification was statistically correlated with the quantitative measured fat/water ratio using Spearman's rank correlation. RESULTS: Statistical analysis of the data revealed only fair correlation of the Goutallier Classification system and the quantitative fat/water ratio with R = 0.35 (p < 0.05). By dichotomizing the scale the correlation was 0.72. The interobserver and intraobserver reliabilities were substantial with R = 0.62 and R = 0.74 (p < 0.01). CONCLUSION: The correlation between the semi quantitative MRI based Goutallier Classification system and MR spectroscopic fat measurement is weak. As an adequate estimation of fatty degeneration based on standard MRI may not be possible, quantitative methods need to be considered in order to increase diagnostic safety and thus provide patients with ideal care in regard to the amount of fatty degeneration. Spectroscopic MR measurement may increase the accuracy of the Goutallier classification and thus improve the prediction of clinical results after rotator cuff repair. However, these techniques are currently only available in an experimental setting. PMID- 27549161 TI - Class I PI3K inhibitor ZSTK474 mediates a shift in microglial/macrophage phenotype and inhibits inflammatory response in mice with cerebral ischemia/reperfusion injury. AB - BACKGROUND: Microglia/macrophages play a critical role in the inflammatory and immune processes of cerebral ischemia/reperfusion injury. Since microglia/macrophages can reversibly shift their phenotype toward either a "detrimental" or a "restorative" state in the injured central nervous system (CNS), compounds mediate that shift which could inhibit inflammation and restore the ability to alleviate cerebral ischemia/reperfusion injury would have therapeutic potential. METHODS: Transient middle cerebral artery occlusion was induced in male C57BL/6 mice. Mice were randomly separated into a sham-operated group, a control group, and a ZSTK474-treated group. We investigated the effect of ZSTK474 by assessing neurological deficits, infarct volume, and histopathological changes. We then determined the potential mechanism by immunofluorescent staining, quantitative real-time polymerase chain reaction (PCR), and Western blot analysis. The Tukey's test or Mann-Whitney U test was used to compare differences among the groups. RESULTS: ZSTK474 alleviated neurological deficits and reduced infarct volume in the cerebral ischemia/reperfusion injury model. Presumably, ZSTK474 shifted the phenotype of microglia/macrophages to a restorative state, since this treatment decreased the secretion of pro-inflammatory factors and advanced the secretion of anti inflammatory factors. These neuroprotective properties of ZSTK474 may be mediated by the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway. CONCLUSIONS: ZSTK474 can mediate a shift in microglia/macrophage phenotype and inhibit the inflammatory response in cerebral ischemia reperfusion injury of mice. These effects appeared to ensue via the PI3K/AKT/mTORC1 pathway. Therefore, ZSTK474 may represent a therapeutic intervention with potential for circumventing the catastrophic aftermath of ischemic stroke. PMID- 27549163 TI - Community perceptions and practices of treatment seeking for childhood pneumonia: a mixed methods study in a rural district, Ghana. AB - BACKGROUND: The World Health Organization recommends community case management of malaria and pneumonia for reduction of under-five mortality in developing countries. Caregivers' perception and understanding of the illness influences the care a sick child receives. Studies in Ghana and elsewhere have routinely shown adequate recognition of malaria by caregivers. Similarly, evidence from Asia and some African countries have shown adequate knowledge on pneumonia. However, in Ghana, little has been documented about community awareness, knowledge, perceptions and management of childhood pneumonia particularly in the Dangme West district. Therefore this formative study was conducted to determine community perceptions of pneumonia for the purpose of informing the design and implementation of context specific health communication strategies to promote early and appropriate care seeking behaviour for childhood pneumonia. METHODS: A mixed method approach was adopted. Data were obtained from structured interviews (N = 501) and eight focus group discussions made up of 56 caregivers of under fives and eight community Key Informants. Descriptive and inference statistics were used for the quantitative data and grounded theory to guide the analysis of the qualitative data. RESULTS: Two-thirds of the respondents had never heard the name pneumonia. Most respondents did not know about the signs and symptoms of pneumonia. For the few who have heard about pneumonia, causes were largely attributed to coming into contact with cold temperature in various forms. Management practices mostly were self-treatment with home remedies and allopathic care. CONCLUSION: The low awareness and inadequate recognition of pneumonia implies that affected children may not receive prompt and appropriate treatment as their caregivers may misdiagnose the illness. Adequate measures need to be taken to create the needed awareness to improve care seeking behaviour. PMID- 27549162 TI - A review of visceral leishmaniasis during the conflict in South Sudan and the consequences for East African countries. AB - BACKGROUND: Visceral leishmaniasis (VL), caused predominantly by Leishmania donovani and transmitted by both Phlebotomus orientalis and Phlebotomus martini, is highly endemic in East Africa where approximately 30 thousands VL cases are reported annually. The largest numbers of cases are found in Sudan - where Phlebotomus orientalis proliferate in Acacia forests especially on Sudan's eastern border with Ethiopia, followed by South Sudan, Ethiopia, Somalia, Kenya and Uganda. Long-standing civil war and unrest is a dominant determinant of VL in East African countries. Here we attempt to identify the correlation between VL epidemics and civil unrest. OBJECTIVE AND METHODOLOGY: In this review, literature published between 1955 and 2016 have been gathered from MSF, UNICEF, OCHA, UNHCR, PubMed and Google Scholar to analyse the correlation between conflict and human suffering from VL, which is especially apparent in South Sudan. FINDINGS: Waves of forced migration as a consequence of civil wars between 1983 and 2005 have resulted in massive and lethal epidemics in southern Sudan. Following a comprehensive peace agreement, but especially with increased allocation of resources for disease treatment and prevention in 2011, cases of VL declined reaching the lowest levels after South Sudan declared independence. However, in the latest epidemic that began in 2014 after the onset of a civil war in South Sudan, more than 1.5 million displaced refugees have migrated internally to states highly endemic for VL, while 800,000 have fled to neighboring countries. CONCLUSION: We find a strong relationship between civil unrest and VL epidemics which tend to occur among immunologically naive migrants entering VL-endemic areas and when Leishmania-infected individuals migrate to new areas and establish additional foci of disease. Further complicating factors in East Africa's VL epidemics include severe lack of access to diagnosis and treatment, HIV/AIDS co infection, food insecurity and malnutrition. Moreover, cases of post-kala-azar dermal leishmaniasis (PKDL) can serve as important reservoirs of anthroponotic Leishmania parasites. PMID- 27549164 TI - Vortexes tune the chirality of graphene oxide and its non-covalent hosts. AB - Graphene oxide (GO) is one of the most appealing bidimensional materials able to interact non-covalently with achiral molecules and to act as chiral inducers. Vortexes can tune chirality and, consequently transfer a specific handedness to non-covalent host molecules, either when dispersed in water or when deposited on a solid surface. PMID- 27549165 TI - A case of U-47700 overdose with laboratory confirmation and metabolite identification. AB - CONTEXT: The opioid epidemic has included use of traditional drugs and recently newer synthetics. It is critically important to recognize and identify these new drugs both clinically and through appropriately designed toxicology testing. There is little available information on a synthetic gaining popularity, U-47700. CASE DETAILS: A 23-year-old female presented after using "U4" by nasal insufflation and injection. She was cyanotic with respiratory depression and responded to naloxone in the field. She was found to have non cardiogenic pulmonary edema and hemoptysis which improved with BiPAP. Urine and serum samples were analyzed using mass spectrometry, confirming 3,4-dichloro-N-[(1R,2R)-2 (dimethylamino)cyclohexyl]-N-methylbenzamide or U-47700. The sample was further analyzed elucidating metabolism specifics. Drug and metabolite concentrations were subsequently measured in both serum and urine. The parent compound of U 47700 was detected at 394 ng/mL and 228 ng/mL in serum and urine, respectively. Metabolites detected in appreciable amounts included the desmethyl (1964 ng/mL in urine), bisdesmethyl (618 ng/mL), desmethyl hydroxy (447 ng/mL), and bisdesmethyl hydroxy forms (247 ng/mL) of U-47700. DISCUSSION: U-47700 is a potent MU-opioid receptor agonist and has recently been used recreationally, contributing to hospitalizations and likely deaths in the community. This is a case report describing an exposure to U-47700 with subsequent laboratory analysis. Based upon this one case, parent U-47700 appear to be an appropriate marker of use in a serum sample. However, demethylated metabolites appear dominant as urinary markers of U-47700 use. PMID- 27549166 TI - Commentary: Fatal French Clinical Trial: What Can We Learn from What Went Wrong? PMID- 27549167 TI - Editorial: Combining Forces to Improve Alzheimer's Disease Drug Discovery: The Symptomatic Battle. PMID- 27549168 TI - Conclusive Article: Sorting the Good from the Bad: The Different Approaches to Predict Cognitive Properties of New Symptomatic Drug Candidates for Neurodegenerative Diseases in Early Development. PMID- 27549169 TI - Dendritic Cells Are Dispensable for T Cell Priming and Control of Acute Lymphocytic Choriomeningitis Virus Infection. AB - Dendritic cells (DCs) are considered to be the major APCs with potent activity for priming of naive CD4 and CD8 T cells. However, T cell priming can also be achieved by other APCs including macrophages, B cells, or even nonhematopoietic cell types. Systemic low-dose infection of mice with lymphocytic choriomeningitis virus (LCMV) results in massive expansion of virus-specific CD4 and CD8 T cells. To determine the role of DCs as APCs and source of type I IFNs in this infection model, we used DeltaDC mice in which DCs are constitutively ablated because of expression of the diphtheria toxin alpha subunit within developing DCs. DeltaDC mice showed lower serum concentrations of IFN-beta and IL-12p40, but normal IFN alpha levels during the first days postinfection. No differences were found for proliferation of transferred TCR-transgenic cells during the early phase of infection, suggesting that T cell priming occurred with the same efficiency in wild-type and DeltaDC mice. Expansion and cytokine expression of endogenous LCMV specific T cells was comparable between wild-type and DeltaDC mice during primary infection and upon rechallenge of memory mice. In both strains of infected mice the viral load was reduced below the limit of detection with the same kinetic. Further, germinal center formation and LCMV-specific Ab responses were not impaired in DeltaDC mice. This indicates that DCs are dispensable as APCs for protective immunity against LCMV infection. PMID- 27549170 TI - The Lymphatic Immune Response Induced by the Adjuvant AS01: A Comparison of Intramuscular and Subcutaneous Immunization Routes. AB - The liposome-based adjuvant AS01 incorporates two immune stimulants, 3-O-desacyl 4'-monophosphoryl lipid A and the saponin QS-21. AS01 is under investigation for use in several vaccines in clinical development. i.m. injection of AS01 enhances immune cell activation and dendritic cell (DC) Ag presentation in the local muscle-draining lymph node. However, cellular and Ag trafficking in the lymphatic vessels that connect an i.m. injection site with the local lymph node has not been investigated. The objectives of this study were: 1) to quantify the in vivo cellular immune response induced by AS01 in an outbred ovine model, 2) to develop a lymphatic cannulation model that directly collects lymphatic fluid draining the muscle, and 3) to investigate the function of immune cells entering and exiting the lymphatic compartments after s.c. or i.m. vaccination with AS01 administered with hepatitis B surface Ag (HBsAg). We show that HBsAg-AS01 induces a distinct immunogenic cellular signature within the blood and draining lymphatics following both immunization routes. We reveal that MHCII(high) migratory DCs, neutrophils, and monocytes can acquire Ag within muscle and s.c. afferent lymph, and that HBsAg-AS01 uniquely induces the selective migration of Ag-positive neutrophils, monocytes, and an MHCII(high) DC-like cell type out of the lymph node via the efferent lymphatics that may enhance Ag-specific immunity. We report the characterization of the immune response in the lymphatic network after i.m. and s.c. injection of a clinically relevant vaccine, all in real time using a dose and volume comparable with that administered in humans. PMID- 27549171 TI - ERbeta-Dependent Direct Suppression of Human and Murine Th17 Cells and Treatment of Established Central Nervous System Autoimmunity by a Neurosteroid. AB - Multiple sclerosis (MS), an autoimmune disease of the CNS, is mediated by autoreactive Th cells. A previous study showed that the neurosteroid dehydroepiandrosterone (DHEA), when administered preclinically, could suppress progression of relapsing-remitting experimental autoimmune encephalomyelitis (EAE). However, the effects of DHEA on human or murine pathogenic immune cells, such as Th17, were unknown. In addition, effects of this neurosteroid on symptomatic disease, as well as the receptors involved, had not been investigated. In this study, we show that DHEA suppressed peripheral responses from patients with MS and reversed established paralysis and CNS inflammation in four different EAE models, including the 2D2 TCR-transgenic mouse model. DHEA directly inhibited human and murine Th17 cells, inducing IL-10-producing regulatory T cells. Administration of DHEA in symptomatic mice induced regulatory CD4(+) T cells that were suppressive in an IL-10-dependent manner. Expression of the estrogen receptor beta by CD4(+) T cells was necessary for DHEA-mediated EAE amelioration, as well as for direct downregulation of Th17 responses. TGF-beta1 as well as aryl hydrocarbon receptor activation was necessary for the expansion of IL-10-producing T cells by DHEA. Thus, our studies demonstrate that compounds that inhibit pathogenic Th17 responses and expand functional regulatory cells could serve as therapeutic agents for autoimmune diseases, such as MS. PMID- 27549172 TI - Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties. AB - Extracellular RNA (exRNA) has been characterized as a molecular alarm signal upon cellular stress or tissue injury and to exert biological functions as a proinflammatory, prothrombotic, and vessel permeability-regulating factor. In this study, we investigated the contribution of exRNA and its antagonist RNase1 in a chronic inflammatory joint disease, rheumatoid arthritis (RA). Upon immunohistochemical inspection of RA, osteoarthritis (OA), and psoriatic arthritis synovium, exRNA was detectable only in the RA synovial lining layer, whereas extracellular DNA was detectable in various areas of synovial tissue. In vitro, exRNA (150-5000 nt) was released by RA synovial fibroblasts (RASF) under hypoxic conditions but not under normoxia or TNF-alpha treatment. RNase activity was increased in synovial fluid from RA and OA patients compared with psoriatic arthritis patients, whereas RNase activity of RASF and OASF cultures was not altered by hypoxia. Reduction of exRNA by RNase1 treatment decreased adhesion of RASF to cartilage, but it had no influence on their cell proliferation or adhesion to endothelial cells. In vivo, treatment with RNase1 reduced RASF invasion into coimplanted cartilage in the SCID mouse model of RA. We also analyzed the expression of neuropilins in synovial tissue and SF, as they may interact with vascular endothelial growth factor signaling and exRNA. The data support the concepts that the exRNA/RNase1 system participates in RA pathophysiology and that RASF are influenced by exRNA in a prodestructive manner. PMID- 27549173 TI - Differential Production of Type I IFN Determines the Reciprocal Levels of IL-10 and Proinflammatory Cytokines Produced by C57BL/6 and BALB/c Macrophages. AB - Pattern recognition receptors detect microbial products and induce cytokines, which shape the immunological response. IL-12, TNF-alpha, and IL-1beta are proinflammatory cytokines, which are essential for resistance against infection, but when produced at high levels they may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine, which dampens proinflammatory responses, but it can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. In this study, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF-alpha, and IL-1beta, but high levels of IL-10, in response to TLR4 and TLR2 ligands LPS and Pam3CSK4, as well as Burkholderia pseudomallei, a Gram-negative bacterium that activates TLR2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN and ERK1/2 dependent, but IL-27-independent, mechanism. Enhanced type I IFN expression in LPS-stimulated C57BL/6 macrophages was accompanied by increased STAT1 and IFN regulatory factor 3 activation. Furthermore, type I IFN contributed to differential IL-1beta and IL-12 production in B. pseudomallei and LPS-stimulated C57BL/6 and BALB/c macrophages via both IL-10-dependent and -independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host. PMID- 27549174 TI - Lymphotoxin beta Receptor Controls T Cell Progenitor Entry to the Thymus. AB - The recruitment of lymphoid progenitors to the thymus is essential to sustain T cell production throughout life. Importantly, it also limits T lineage regeneration following bone marrow transplantation, and so contributes to the secondary immunodeficiency that is caused by delayed immune reconstitution. Despite this significance, the mechanisms that control thymus colonization are poorly understood. In this study, we show that in both the steady-state and after bone marrow transplant, lymphotoxin beta receptor (LTbetaR) controls entry of T cell progenitors to the thymus. We show that this requirement maps to thymic stroma, further underlining the key importance of this TNFR superfamily member in regulation of thymic microenvironments. Importantly, analysis of the requirement for LTbetaR in relationship to known regulators of thymus seeding suggests that it acts independently of its regulation of thymus-homing chemokines. Rather, we show that LTbetaR differentially regulates intrathymic expression of adhesion molecules known to play a role in T cell progenitor entry to the thymus. Finally, Ab-mediated in vivo LTbetaR stimulation following bone marrow transplant enhances initial thymus recovery and boosts donor-derived T cell numbers, which correlates with increased adhesion molecule expression by thymic stroma. Collectively, we reveal a novel link between LTbetaR and thymic stromal cells in thymus colonization, and highlight its potential as an immunotherapeutic target to boost T cell reconstitution after transplantation. PMID- 27549175 TI - Timing of Radioactive Iodine Administration Does Not Influence Outcomes in Patients with Differentiated Thyroid Carcinoma. AB - BACKGROUND: Radioactive iodine (RAI) is widely used in the management of differentiated thyroid cancer (DTC). The impact of the time interval between total thyroidectomy (TT) and RAI administration on disease outcome remains controversial. The objective of the present study was to evaluate the impact of the time interval between TT and RAI. METHODS: This study evaluated a cohort of DTC patients who received RAI therapy for whom data on disease status were available. Patients were allocated to one of two groups, according to the time interval between TT and RAI. "Disease-free" was defined as no clinical, imaging, or biochemical evidence of thyroid cancer. RESULTS: The study included 545 individuals. The TNM stages were: 322 (59.1%) patients in Stage I, 62 (11.4%) in Stage II, 65 (11.9%) in Stage III, and 82 (15.0%) in Stage IV. The median time interval between TT and RAI was six months (P25-75: 3-10 months). Patients were allocated to one of two groups according to RAI timing administration: group A <=6 months after TT (median 3 months; n = 295), or group B >6 months after TT (median 10.5 months; n = 250). There were no differences for sex, histological type, tumor size, distant metastasis, or RAI dose between the groups (p > 0.1). Patients in group B were older (47.1 vs. 43.1 years; p = 0.02), had less cervical metastasis (73.6% vs. 59.3%; p = 0.002), and were more commonly classified as low ATA risk (48.0% vs. 36.6%; p = 0.027). One year after initial therapy, 59.3% and 65.6% of patients in groups A and B, respectively, were considered disease-free (p = 0.15). Remarkably, the percentage of patients classified as disease-free was similar, even when analyzing a subgroup of high-risk patients (n = 72; 9.5% vs. 10.0%; p = 1.0). These findings did not change after a median of six years of follow-up. Accordingly, further analysis by multiple logistic regression showed that timing of RAI was not associated with persistent disease (relative risk 0.97 [confidence interval 0.80-1.19]). CONCLUSIONS: Timing of RAI does not seem to interfere with the disease outcomes in DTC and can therefore be safely planned while taking into account the health system logistics. PMID- 27549176 TI - Performance and prognostic utility of the 92-gene assay in the molecular subclassification of ampullary adenocarcinoma. AB - BACKGROUND: Ampullary adenocarcinoma is a rare gastrointestinal cancer associated with diverse outcomes due to clinical and pathological heterogeneity. Standardized methods to better prognosticate and inform therapeutic selection for ampullary adenocarcinoma are needed. This study explored the novel use and potential prognostic utility of a 92-gene cancer classifier in ampullary adenocarcinomas. METHODS: In this prospectively-defined, blinded study of ampullary adenocarcinoma [N =54; stage T3 or higher (57 %); Grade III (44 %); Node positive (55 %)], the performance of a 92-gene classifier was examined to predict the ampullary subtype that was derived from histomorphological examination of resected ampullary samples. Outcome data for relapse-free survival (RFS) and overall survival (OS) were plotted to compare the prognostic utility of histological subtyping, histomolecular phenotyping, and the 92-gene classifier. Multivariate analysis was used to determine clinicopathological variables that were independently associated with overall survival. RESULTS: The 92-gene classifier demonstrated sensitivities and specificities of 85 % [95 % CI, 66-94] and 68 % [95 % CI, 48-84] and 64 % [95 % CI, 46-79] and 88 % [95 % CI, 70-98] for the pancreaticobiliary and intestinal histological subtypes, respectively. For the 92-gene classifier, improved outcomes were observed for the intestine versus the pancreaticobiliary prediction (median OS 108.1 v 36.4 months; HR, 2.17; 95 % CI, 0.98 to 4.79; P = 0.05). Similar results were seen for ampullary adenocarcinoma stratification by histological subtype (P = 0.04) and histomolecular phenotype (P = 0.02). Within poorly differentiated ampullary adenocarcinomas only the 92-gene classifier demonstrated statistically significant differences in RFS and OS (P < 0.05). CONCLUSIONS: Prognostic stratification of ampullary adenocarcinoma was similar for the 92-gene classifier, histological subtype, and histomolecular phenotype. The 92-gene classifier provides an unbiased standardized molecular-based approach to stratify ampullary tumors. PMID- 27549177 TI - Assigning breed origin to alleles in crossbred animals. AB - BACKGROUND: For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. RESULTS: The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. CONCLUSIONS: The BOA approach accurately assigns breed origin to alleles of crossbred animals, even if their pedigree is not recorded. PMID- 27549178 TI - Noninvasive ventilation with helmet versus control strategy in patients with acute respiratory failure: a systematic review and meta-analysis of controlled studies. AB - BACKGROUND: Noninvasive ventilation (NIV) has proved to be a useful technique for breathing support. However, complications, discomfort, and failure of NIV were commonly caused by the mask. Therefore, the helmet was developed to improve performance and reduce complications; however, there has been no conclusive results on its effect until now. Thus, we performed a systematic review and meta analysis to investigate the effect of NIV with a helmet versus the control strategy in patients with acute respiratory failure (ARF). METHODS: We searched Cochrane Library, PubMed, Ovid, and Embase databases and bibliographies of relevant articles published before June 2016. Randomized and case-control studies that adopted the helmet as an NIV interface and compared it with another interface were included. The primary outcomes were hospital mortality, intubation rate, and complications. The secondary outcomes included the length of intensive care unit (ICU) stay, gas exchange, and respiratory rate. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by the Mantel-Haenszel method and mean difference by the inverse variance method in a fixed effect model or random effects model according to the heterogeneity. RESULTS: A total of 11 studies involving 621 patients were included. The overall hospital mortality was 17.53 % in the helmet NIV group versus 30.67 % in the control group. Use of the helmet was associated with lower hospital mortality (OR 0.43, 95 % CI 0.26 to 0.69, p = 0.0005), intubation rate (OR 0.32, 95 % CI 0.21 to 0.47, P < 0.00001), and complications (OR 0.6, 95 % CI 0.4 to 0.92, P = 0.02). In contrast, there was no significant difference in gas exchange and ICU stay (P >0.05). Subgroup analysis found the helmet reduced mortality mainly in hypoxemic ARF patients (P < 0.05) and a lower intubation rate was shown in randomized trials; fewer complications caused by the helmet might be restricted to case-control trials. Additionally, the effect of the helmet on PaCO2 was influenced by type of ARF and ventilation mode (P <0.00001). CONCLUSION: NIV with a helmet was associated with reduced hospital mortality and intubation requirement. The helmet was as effective as the mask in gas exchange with no additional advantage. Large randomized controlled trials are needed to provide more robust evidence. PMID- 27549179 TI - Maternal hyperglycemia during labor and related immediate post-partum maternal and perinatal outcomes at the Yaounde Central Hospital, Cameroon. AB - BACKGROUND: Data on the prevalence and complications of gestational diabetes are very scarce in Cameroon. The aim of this study was to evaluate the uptake of screening for gestational diabetes and assess the immediate post-partum outcome of hyperglycemic parturient mothers and perinatal outcome of their babies. METHODS: A prospective cohort study was held at the Maternity of the Yaounde Central Hospital from March to June 2013. One hundred volunteer women in labor without overt diabetes mellitus and having fasted for 8 to 12 h were recruited. No intervention was given. A clinical examination was done and capillary glucose recorded. Parturient women were categorized into two groups (hyperglycemic and non-hyperglycemic subjects) based on glycemia results interpreted according to the International Association of Diabetes and Pregnancy Study Groups. Mothers' clinical examination was repeated and neonates examined immediately after delivery. Perinatal outcomes associated with maternal hyperglycemia during labor were assessed using relative risks. A p value <0.05 was considered statistically significant. RESULTS: One hundred women with a mean age of 27 (SD 6) years were recruited. Of them, 22 (22 %) had already been screened for gestational diabetes at baseline. Thirty-one (31 %) were diagnosed with hyperglycemia during labor, and this condition was highly associated with macrosomia in neonates (RR = 8.9, 95 % CI 2.70-29.32; p < 0.001). Other complications associated with maternal hyperglycemia during labor were perineal tears, cesarean section, and intrauterine fetal death, though the association was not statistically significant. CONCLUSIONS: The main finding of this study is that maternal hyperglycemia during labor is highly associated with macrosomia in neonates. About a third of mothers were concerned with hyperglycemia during labor, and gestational diabetes was insufficiently screened in this series. PMID- 27549181 TI - Malignant pancreatic serous cystic neoplasms: systematic review with a new case. AB - BACKGROUND: This study analyzes the clinicopathologic and radiologic characteristics of malignant serous cystic neoplasm (SCN) of the pancreas through systematic review and an institutional case report. METHODS: A comprehensive literature search was performed in the MEDLINE database to identify studies on malignant SCNs of the pancreas that had detailed clinicopathologic and radiologic information. A computerized systematic search of our institutional database was also performed to identify cases of malignant SCN for addition to the systematic review. Using the final included cases, we analyzed the clinicopathologic and radiologic features of malignant SCNs of the pancreas. RESULTS: A review of 136 candidate articles identified 26 studies with 26 cases that had detailed clinical information. Our institutional data search added one case. The systematic review of the 27 cases revealed that primary tumors (mean diameter 10.2 +/- 4.0 cm) mainly involved the body and tail of the pancreas (n = 16) and frequently invaded adjacent organs (n = 19). Distant metastases occurred in 14 patients (synchronous, n = 5; metachronous, n = 8; both, n = 1), most commonly in the liver (n = 13). Imaging features of malignant SCNs of the pancreas were identical to the benign counterpart, except local invasion or distant metastases. The prognosis was excellent in that 17 were alive at the time of writing with a median follow-up period of 2 years. CONCLUSIONS: The malignant potential of SCNs of the pancreas should be considered in the diagnosis and management of patients with pancreatic SCNs. PMID- 27549182 TI - Inferring extrinsic noise from single-cell gene expression data using approximate Bayesian computation. AB - BACKGROUND: Gene expression is known to be an intrinsically stochastic process which can involve single-digit numbers of mRNA molecules in a cell at any given time. The modelling of such processes calls for the use of exact stochastic simulation methods, most notably the Gillespie algorithm. However, this stochasticity, also termed "intrinsic noise", does not account for all the variability between genetically identical cells growing in a homogeneous environment. Despite substantial experimental efforts, determining appropriate model parameters continues to be a challenge. Methods based on approximate Bayesian computation can be used to obtain posterior parameter distributions given the observed data. However, such inference procedures require large numbers of simulations of the model and exact stochastic simulation is computationally costly. In this work we focus on the specific case of trying to infer model parameters describing reaction rates and extrinsic noise on the basis of measurements of molecule numbers in individual cells at a given time point. RESULTS: To make the problem computationally tractable we develop an exact, model specific, stochastic simulation algorithm for the commonly used two-state model of gene expression. This algorithm relies on certain assumptions and favourable properties of the model to forgo the simulation of the whole temporal trajectory of protein numbers in the system, instead returning only the number of protein and mRNA molecules present in the system at a specified time point. The computational gain is proportional to the number of protein molecules created in the system and becomes significant for systems involving hundreds or thousands of protein molecules. CONCLUSIONS: We employ this simulation algorithm with approximate Bayesian computation to jointly infer the model's rate and noise parameters from published gene expression data. Our analysis indicates that for most genes the extrinsic contributions to noise will be small to moderate but certainly are non-negligible. PMID- 27549180 TI - Neuroprotective effect of nerolidol against neuroinflammation and oxidative stress induced by rotenone. AB - BACKGROUND: Parkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60. The etiology of the disease is unknown; however, accumulating evidence suggests that mitochondrial defects, oxidative stress, and neuroinflammation play important roles in developing the disease. Current medications for PD can only improve its symptoms, but are unable to halt its progressive nature. Although many therapeutic approaches are available, new drugs are urgently needed for the treatment of PD. Thus, the present study was undertaken to investigate the neuroprotective potential of nerolidol, a sesquiterpene alcohol, on a rotenone-induced experimental model of PD, where male Wistar rats intraperitoneally received rotenone (ROT) at a dose of 2.5 mg/kg of body weight once daily for 4 weeks. RESULTS: Nerolidol, which has antioxidant and anti-inflammatory properties, was injected intraperitoneally at 50 mg/kg of body weight, once daily for 4 weeks, and at 30 min prior to ROT administration. ROT administration significantly reduced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of the antioxidant tripeptide glutathione (GSH). Moreover, ROT increased the levels of the lipid peroxidation product malondialdehyde (MDA), proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and inflammatory mediators (COX-2 and iNOS) in rat brain tissues. Immunostaining of brain tissue sections revealed a significant increase in the number of activated astrocytes (GFAP) and microglia (Iba-1), along with the concomitant loss of dopamine (DA) neurons in the substantia nigra pars compacta and dopaminergic nerve fibers in the striatum of ROT-treated rats. As expected, nerolidol supplementation to ROT-injected rats significantly increased the level of SOD, CAT, and GSH, and decreased the level of MDA. Nerolidol also inhibited the release of proinflammatory cytokines and inflammatory mediators. Finally, nerolidol treatment prevented ROT-induced glial cell activation and the loss of dopaminergic neurons and nerve fibers, and ultimately attenuated ROT induced dopaminergic neurodegeneration. CONCLUSION: Our findings are the first to show that the neuroprotective effect of nerolidol is mediated through its anti oxidant and anti-inflammatory activities, which strongly supports its therapeutic potential for the treatment of PD. PMID- 27549184 TI - Cu-Catalyzed Three-Component Coupling of Aryne, Alkyne, and Benzenesulfonothioate: Modular Synthesis of o-Alkynyl Arylsulfides. AB - A copper-catalyzed three-component coupling reaction of in situ formed arynes, terminal alkynes, and benzenesulfonothioates is described. This reaction provides an efficient modular synthesis of o-alkynyl arylsulfides from easily available starting materials. This process involves one C-S bond and one C-C bond formation in one pot. PMID- 27549185 TI - Knowledge, attitudes and practices regarding HIV/AIDS among senior secondary school students in Fako Division, South West Region, Cameroon. AB - BACKGROUND: Knowledge, attitudes and practices (KAPs) regarding HIV/AIDS is one of the corner stones in the fight against the disease. Youths are most vulnerable to infection because they engage in risky practices due to a lack of adequate information. Thus, evaluating their KAPs will help in designing appropriate prevention strategies. This study was aimed at assessing the KAPs of senior secondary school students in Fako Division, Cameroon, on HIV/AIDS. METHODS: This was a cross-sectional study carried out on 464 students aged 13-25 years, selected by systematic quota random sampling from some secondary schools in Fako, from April to June 2014, to evaluate their KAPs regarding HIV/AIDS. Participants were drawn from one secondary school in each of the four health districts in Fako. Pre-tested questionnaires were administered to the students to obtain information about their KAPs on HIV/AIDS. Data were analyzed using SPSS version 20.0. RESULTS: All respondents were aware of HIV/AIDS. Sources of information varied, the most common being sex education in school. The majority of participants demonstrated an adequate understanding of HIV transmission and prevention. However, misconceptions about routes of transmission were observed in 3.4 to 23.3 % of respondents. Risky behaviors were found among participants as about 60 % practice safe sex and 40 % reported not to. Up to 196 (42.2 %) respondents had a history of sexual intercourse of which 108 (56.25 %) had used a condom during their last three sexual encounters. About half of the respondents had negative views about HIV infected people. Students with medium (34.3 %) and high (62.1 %) levels of knowledge were more likely to display positive attitudes Although statistically not significant, we found that as knowledge increased the ability of respondents to report safer sex decreased (95 % CI, P = 0.922). CONCLUSIONS: Students had a satisfactory level of knowledge on HIV/AIDS prevention. Those with adequate knowledge were more likely to display positive attitudes towards PLHIV. Having adequate knowledge did not imply engaging in safe practices. This study none-the-less highlighted some misconceptions about HIV transmission, intolerant and discriminatory attitudes towards PLHIV, and risky sexual practices among study participants which can be corrected by reinforcing sex education curriculum as sex education in school was their main source of information on HIV/AIDS. PMID- 27549183 TI - Metachronous bladder metastases of a type 2 papillary renal cell carcinoma: a case report and review of the literature. AB - BACKGROUND: Renal cell carcinoma developing metastases in the bladder is rare. Bladder metastasis due to a papillary type of renal cell carcinoma is rarer. Such metastases could be synchronous or metachronous. CASE PRESENTATION: Here we present a 55-year-old female patient with haematuria who underwent left nephro ureterectomy for a suspected urothelial tumour. Histopathology revealed it to be a type 2 papillary renal cell carcinoma. Eighteen months later, she developed metachronous bladder metastasis of the papillary renal cell carcinoma which was treated with total cystectomy. Currently, she is on interferon therapy. CONCLUSIONS: These bladder metastases from renal cell carcinoma could be due to drop metastases, lymphatic spread or haematogenous spread. The exact mechanism in a given case appears to be unpredictable. PMID- 27549186 TI - Development of Xe and Kr empirical potentials for CeO2, ThO2, UO2 and PuO2, combining DFT with high temperature MD. AB - The development of embedded atom method (EAM) many-body potentials for actinide oxides and associated mixed oxide (MOX) systems has motivated the development of a complementary parameter set for gas-actinide and gas-oxygen interactions. A comprehensive set of density functional theory (DFT) calculations were used to study Xe and Kr incorporation at a number of sites in CeO2, ThO2, UO2 and PuO2. These structures were used to fit a potential, which was used to generate molecular dynamics (MD) configurations incorporating Xe and Kr at 300 K, 1500 K, 3000 K and 5000 K. Subsequent matching to the forces predicted by DFT for these MD configurations was used to refine the potential set. This fitting approach ensured weighted fitting to configurations that are thermodynamically significant over a broad temperature range, while avoiding computationally expensive DFT-MD calculations. The resultant gas potentials were validated against DFT trapping energies and are suitable for simulating combinations of Xe and Kr in solid solutions of CeO2, ThO2, UO2 and PuO2, providing a powerful tool for the atomistic simulation of conventional nuclear reactor fuel UO2 as well as advanced MOX fuels. PMID- 27549187 TI - Humanitarian Assistance and Disaster Relief mission by a tripartite medical team led by the Singapore Armed Forces after the 2015 Nepal earthquake. AB - INTRODUCTION: This study aimed to report the injury or disease patterns, challenges, key observations, and recommendations by the Singapore Armed Forces (SAF) team that embarked on an Humanitarian Assistance and Disaster Relief (HADR) mission in the aftermath of the April 2015 Nepal earthquake. METHODS: The SAF medical team that provided HADR assistance to Nepal consisted of personnel from the SAF, Singaporecs Ministry of Health and the Royal Brunei Armed Forces. Upon arrival in Kathmandu, Nepal, the SAF medical team was assigned to the Gokarna district by the local health authorities. In addition to providing primary healthcare, the medical facility was equipped to perform resuscitation and minor procedures. We also assembled mobile medical teams (MMTs) that travelled to various remote areas of the country to deliver medical aid. RESULTS: A total of 3,014 patients were managed by the SAF medical team. Of these patients, 1,286 (42.7%) were men. 574 (19.0%) patients sustained earthquake-related injuries or illnesses, while 2,440 (81.0%) sustained non-earthquake-related injuries or illnesses. The team treated a total of 447 (77.9%) adults and 127 (22.1%) paediatric patients with earthquake-related injuries or illnesses. A significant number of patients developed exacerbations of underlying medical conditions. 2,161 (71.7%) patients were treated in our main facility in Gokarna, while 853 patients (28.3%) were treated by our MMTs. CONCLUSION: The ability to transport healthcare personnel and essential medical equipment within a short time allowed the SAF medical team to provide crucial medical care in the aftermath of the 2015 Nepal earthquake. PMID- 27549190 TI - Applicability of the theory of planned behavior in explaining the general practitioners eLearning use in continuing medical education. AB - BACKGROUND: General practitioners (GP) update their knowledge and skills by participating in continuing medical education (CME) programs either in a traditional or an e-Learning format. GPs' beliefs about electronic format of CME have been studied but without an explicit theoretical framework which makes the findings difficult to interpret. In other health disciplines, researchers used theory of planned behavior (TPB) to predict user's behavior. METHODS: In this study, an instrument was developed to investigate GPs' intention to use e Learning in CME based on TPB. The goodness of fit of TPB was measured using confirmatory factor analysis and the relationship between latent variables was assessed using structural equation modeling. RESULTS: A total of 148 GPs participated in the study. Most of the items in the questionnaire related well to the TPB theoretical constructs, and the model had good fitness. The perceived behavioral control and attitudinal constructs were included, and the subjective norms construct was excluded from the structural model. The developed questionnaire could explain 66 % of the GPs' intention variance. CONCLUSIONS: The TPB could be used as a model to construct instruments that investigate GPs' intention to participate in e-Learning programs in CME. The findings from the study will encourage CME managers and researchers to explore the developed instrument as a mean to explain and improve the GPs' intentions to use eLearning in CME. PMID- 27549189 TI - Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity. AB - BACKGROUND: Histone deacetylase inhibitors (HDACi) exert multiple cytotoxic actions on cancer cells. Currently, different synthetic HDACi are in clinical use or clinical trials; nevertheless, since both pro-invasive and anti-invasive activities have been described, there is some controversy about the effect of HDACi on melanoma cells. METHODS: Matrigel and Collagen invasion assays were performed to evaluate the effect of several HDACi (Butyrate, Trichostatin A, Valproic acid and Vorinostat) on two human melanoma cell line invasion (A375 and HT-144). The expression of N- and E-Cadherin and the activity of the RhoA GTPase were analyzed to elucidate the mechanisms involved in the HDACi activity. RESULTS: HDACi showed a pro-invasive effect on melanoma cells in vitro. This effect was accompanied by an up-regulation of N-cadherin expression and an inhibition of RhoA activity. Moreover, the down-regulation of N-cadherin through blocking antibodies or siRNA abrogated the pro-invasive effect of the HDACi and, additionally, the inhibition of the Rho/ROCK pathway led to an increase of melanoma cell invasion similar to that observed with the HDACi treatments. CONCLUSION: These results suggest a role of N-cadherin and RhoA in HDACi induced invasion and call into question the suitability of some HDACi as antitumor agents for melanoma patients. PMID- 27549188 TI - Delayed hemobilia due to hepatic artery pseudo-aneurysm: a pitfall of laparoscopic cholecystectomy. AB - BACKGROUND: Hepatic artery pseudoaneurysm as a complication of laparoscopic cholecystectomy is considered a rare, potentially life threatening condition. CASE PRESENTATION: We report a case of late onset hemobilia presenting 8 months following elective laparoscopic cholecystectomy with complex biliary and vascular injury. The patient was treated surgically with primary repair of the aneurysm and hepaticojujenostomy. CONCLUSION: A high index of suspicion should be raised when encountering a patient with massive upper GI bleeding and a previous history of hepatobiliary manipulation or surgery regardless of postoperative period. PMID- 27549191 TI - Insight on the larval habitat of Afrotropical Culicoides Latreille (Diptera: Ceratopogonidae) in the Niayes area of Senegal, West Africa. AB - BACKGROUND: Certain biting midges species of the genus Culicoides (Diptera: Ceratopogonidae) are vectors of virus to livestock worldwide. Culicoides larval ecology has remained overlooked because of difficulties to identify breeding sites, methodological constraints to collect samples and lack of morphological tools to identify field-collected individuals to the species level. After the 2007 unforeseen outbreaks of African horse sickness virus (AHSV) in Senegal (West Africa), there is a need to identify suitable and productive larval habitats in horse farms for the main Culicoides species to evaluate the implementation of vector control measures or preventive actions. METHODS: We investigate twelve putative larval habitats (habitat types) of Culicoides inside and outside of three horse farms in the Niayes area of Senegal using a combination of flotation and emergence methods during four collection sessions. RESULTS: Among the three studied horse farms, three habitat types were found positive for Culicoides larvae: pond edge, lake edge and puddle edge. A total of 1420 Culicoides individuals (519?/901?) belonging to ten species emerged from the substrate samples. Culicoides oxystoma (40 %), C. similis (25 %) and C. nivosus (24 %) were the most abundant species and emerged from the three habitat types while C. kingi (5 %) was only retrieved from lake edges and one male emerged from puddle edge. Culicoides imicola (1.7 %) was found in low numbers and retrieved only from pond and puddle edges. CONCLUSIONS: Larval habitats identified were not species specific. All positive larval habitats were found outside the horse farms. This study provides original baseline information on larval habitats of Culicoides species in Senegal in an area endemic for AHSV, in particular for species of interest in animal health. These data will serve as a point of reference for future investigations on larval ecology and larval control measures. PMID- 27549192 TI - Mutagenesis of N-terminal residues of feline foamy virus Gag reveals entirely distinct functions during capsid formation, particle assembly, Gag processing and budding. AB - BACKGROUND: Foamy viruses (FVs) of the Spumaretrovirinae subfamily are distinct retroviruses, with many features of their molecular biology and replication strategy clearly different from those of the Orthoretroviruses, such as human immunodeficiency, murine leukemia, and human T cell lymphotropic viruses. The FV Gag N-terminal region is responsible for capsid formation and particle budding via interaction with Env. However, the critical residues or motifs in this region and their functional interaction are currently ill-defined, especially in non primate FVs. RESULTS: Mutagenesis of N-terminal Gag residues of feline FV (FFV) reveals key residues essential for either capsid assembly and/or viral budding via interaction with the FFV Env leader protein (Elp). In an in vitro Gag-Elp interaction screen, Gag mutations abolishing particle assembly also interfered with Elp binding, indicating that Gag assembly is a prerequisite for this highly specific interaction. Gradient sedimentation analyses of cytosolic proteins indicate that wild-type Gag is mostly assembled into virus capsids. Moreover, proteolytic processing of Gag correlates with capsid assembly and is mostly, if not completely, independent from particle budding. In addition, Gag processing correlates with the presence of packaging-competent FFV genomic RNA suggesting that Pol encapsidation via genomic RNA is a prerequisite for Gag processing. Though an appended heterogeneous myristoylation signal rescues Gag particle budding of mutants unable to form capsids or defective in interacting with Elp, it fails to generate infectious particles that co-package Pol, as evidenced by a lack of Gag processing. CONCLUSIONS: Changes in proteolytic Gag processing, intracellular capsid assembly, particle budding and infectivity of defined N terminal Gag mutants highlight their essential, distinct and only partially overlapping roles during viral assembly and budding. Discussion of these findings will be based on a recent model developed for Gag-Elp interactions in prototype FV. PMID- 27549193 TI - Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. AB - BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER . CONCLUSIONS: We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies. PMID- 27549195 TI - Self-assembled sulfur/reduced graphene oxide nanoribbon paper as a free-standing electrode for high performance lithium-sulfur batteries. AB - Flexible, interconnected sulfur/reduced graphene oxide nanoribbon paper (S/RGONRP) is synthesized through S2- reduction and evaporation induced self assembly processes. The in situ formed sulfur atoms chemically bonded with the surface of reduced graphene oxide nanoribbons and were physically trapped by the compact assembly, which make the hybrid a suitable cathode material for lithium sulfur batteries. PMID- 27549194 TI - Additive methods for genomic signatures. AB - BACKGROUND: Studies exploring the potential of Chaos Game Representations (CGR) of genomic sequences to act as "genomic signatures" (to be species- and genome specific) showed that CGR patterns of nuclear and organellar DNA sequences of the same organism can be very different. While the hypothesis that CGRs of mitochondrial DNA sequences can act as genomic signatures was validated for a snapshot of all sequenced mitochondrial genomes available in the NCBI GenBank sequence database, to our knowledge no such extensive analysis of CGRs of nuclear DNA sequences exists to date. RESULTS: We analyzed an extensive dataset, totalling 1.45 gigabase pairs, of nuclear/nucleoid genomic sequences (nDNA) from 42 different organisms, spanning all major kingdoms of life. Our computational experiments indicate that CGR signatures of nDNA of two different origins cannot always be differentiated, especially if they originate from closely-related species such as H. sapiens and P. troglodytes or E. coli and E. fergusonii. To address this issue, we propose the general concept of additive DNA signature of a set (collection) of DNA sequences. One particular instance, the composite DNA signature, combines information from nDNA fragments and organellar (mitochondrial, chloroplast, or plasmid) genomes. We demonstrate that, in this dataset, composite DNA signatures originating from two different organisms can be differentiated in all cases, including those where the use of CGR signatures of nDNA failed or was inconclusive. Another instance, the assembled DNA signature, combines information from many short DNA subfragments (e.g., 100 basepairs) of a given DNA fragment, to produce its signature. We show that an assembled DNA signature has the same distinguishing power as a conventionally computed CGR signature, while using shorter contiguous sequences and potentially less sequence information. CONCLUSIONS: Our results suggest that, while CGR signatures of nDNA cannot always play the role of genomic signatures, composite and assembled DNA signatures (separately or in combination) could potentially be used instead. Such additive signatures could be used, e.g., with raw unassembled next-generation sequencing (NGS) read data, when high-quality sequencing data is not available, or to complement information obtained by other methods of species identification or classification. PMID- 27549197 TI - Developmental and Evolutionary Origins of the Amniote Phallus. AB - An intromittent phallus is used for sperm transfer in most amniote taxa; however, there is extensive variation in external genital morphology within and among the major amniote clades. Amniote phalluses vary in number (paired, single, or rudimentary), spermatic canal morphology (closed tube or open sulcus), and mode of transition between resting and tumescent states (inflation, rotation, eversion, or muscle relaxation). In a phylogenetic context, these varying adult anatomies preclude a clear interpretation for the evolutionary history of amniote external genitalia; as such, multiple hypotheses have been presented for the origin(s) of the amniote phallus. In combination with historic embryological studies, recent comparative developmental analyses have uncovered evidence that, despite extensive morphological variation in adult anatomy, embryonic patterning of the external genitalia is similar among amniotes and begins with emergence of paired swellings adjacent to the cloaca. External genital development in mammals, squamates (lizards, snakes, and amphisbaenians), Rhyncocephalians (tuataras), turtles, crocodilians (alligators, crocodiles, and gharials), and birds proceeds by iterative sequences of budding and fusion events, initiated by emergence of paired swellings adjacent to the embryonic cloaca. Conservation of the embryonic origins, morphogenetic processes, and molecular genetic mechanisms involved in external genital development across Amniota supports derivation from the common ancestor of amniotes, and suggests that lineage-specific divergence of later patterning events underlies the variation observed in extant adult amniote phallus morphology. PMID- 27549196 TI - Arabidopsis protein disulfide isomerase-8 is a type I endoplasmic reticulum transmembrane protein with thiol-disulfide oxidase activity. AB - BACKGROUND: In eukaryotes, classical protein disulfide isomerases (PDIs) facilitate the oxidative folding of nascent secretory proteins in the endoplasmic reticulum by catalyzing the formation, breakage, and rearrangement of disulfide bonds. Terrestrial plants encode six structurally distinct subfamilies of PDIs. The novel PDI-B subfamily is unique to terrestrial plants, and in Arabidopsis is represented by a single member, PDI8. Unlike classical PDIs, which lack transmembrane domains (TMDs), PDI8 is unique in that it has a C-terminal TMD and a single N-terminal thioredoxin domain (instead of two). No PDI8 isoforms have been experimentally characterized to date. Here we describe the characterization of the membrane orientation, expression, sub-cellular localization, and biochemical function of this novel member of the PDI family. RESULTS: Histochemical staining of plants harboring a PDI8 promoter:beta-glucuronidase (GUS) fusion revealed that the PDI8 promoter is highly active in young, expanding leaves, the guard cells of cotyledons, and in the vasculature of several organs, including roots, leaves, cotyledons, and flowers. Immunoelectron microscopy studies using a PDI8-specific antibody on root and shoot apical cells revealed that PDI8 localizes to the endoplasmic reticulum (ER). Transient expression of two PDI8 fusions to green fluorescent protein (spGFP-PDI8 and PDI8-GFP-KKED) in leaf mesophyll protoplasts also resulted in labeling of the ER. Protease protection immunoblot analysis indicated that PDI8 is a type I membrane protein, with its catalytic domain facing the ER lumen. The lumenal portion of PDI8 was able to functionally complement the loss of the prokaryotic protein foldase, disulfide oxidase (DsbA), as demonstrated by the reconstitution of periplasmic alkaline phosphatase in Escherichia coli. CONCLUSION: The results indicate that PDI8 is a type I transmembrane protein with its catalytic domain facing the lumen of the ER and functions in the oxidation of cysteines to produce disulfide bonds. It likely plays a role in folding newly-synthesized secretory proteins as they translocate across the ER membrane into the lumen. These foundational results open the door to identifying the substrates of PDI8 to enable a more thorough understanding of its function in plants. PMID- 27549198 TI - A Comparison of Resources for the Annotation of a De Novo Assembled Transcriptome in the Molting Gland (Y-Organ) of the Blackback Land Crab, Gecarcinus lateralis. AB - Next-generation sequencing technologies are revolutionizing crustacean biology. De novo assembly of RNA sequencing (RNA-seq) data allows researchers to catalog and quantify genes expressed in tissues of a species that lacks a complete genome sequence. RNA-seq has become an important tool for understanding phenotypic plasticity and the responses of organisms to environmental cues. However, there are challenges with identification of assembled contiguous sequences (contigs) without a reference genome. Thus, the selection of resources for annotating contigs is critical for the downstream analysis of gene functions. A de novo assembled transcriptome of the Gecarcinus lateralis molting gland, or Y-organ (YO), was used to compare two functional annotation packages, Trinotate and Blast2GO. The assembled transcriptome contained 229,278 contigs derived from YOs from animals in intermolt, premolt (early, mid, and late), and postmolt stages. Gene identification using BLAST against four databases and functional annotation using Gene Ontologies were conducted. The analysis revealed two major limitations of de novo assembly: (1) assembly using Trinity generates redundant contigs and (2) transcripts that encode protein isoforms are not distinguished with current computational tools. It is recommended that the NCBI Non-Redundant, SwissProt, TrEMBL, and Uniref90 databases be used to maximize gene identification. Trinotate is preferred for assigning functions to identified genes, as the package uses multiple databases for annotation. The differences between packages to generate Gene Ontology (GO) terms are attributed to the databases used for inputs: Trinotate uses both Pfam and BLAST databases, while Blast2GO uses only the BLAST database. InterProScan was used to verify the GO terms assigned via BLAST. A comprehensive annotation of de novo assembled transcriptome is necessary for the downstream analysis of differentially expressed transcripts in the YO over the molt cycle. PMID- 27549199 TI - Modeling the Importance of Sample Size in Relation to Error in MHC-Based Mate Choice Studies on Natural Populations. AB - Understanding the genetic basis of mate choice in natural populations is a challenging undertaking. Mechanistic investigations of neural and genetic exemplars must be interpreted in the context of population-level effects, and complex demographic and ecological processes that may mask MHC-based mate-choice effects. This is particularly exacerbated in highly polymorphic MHC-based mate choice studies, which require a large sample size to sufficiently characterize an allele distribution in a population, and typically yield small effect sizes. A careful consideration of sample size, statistical power, and effect size is therefore critical for correctly interpreting conclusions in this field. To address these concerns, we used Monte Carlo randomization tests to investigate the effects of sample size on a simulated population of breeding organisms with intermediate MHC polymorphism. We illustrate the impact of sample size on error rates and effect sizes, and highlight the potential for incorrect conclusions in the existing literature. PMID- 27549200 TI - Examining the Effects of Chromatic Aberration, Object Distance, and Eye Shape on Image-Formation in the Mirror-Based Eyes of the Bay Scallop Argopecten irradians. AB - The eyes of scallops form images using a concave spherical mirror and contain two separate retinas, one layered on top of the other. Behavioral and electrophysiological studies indicate that the images formed by these eyes have angular resolutions of about 2 degrees . Based on previous ray-tracing models, it has been thought that the more distal of the two retinas lies near the focal point of the mirror and that the proximal retina, positioned closer to the mirror at the back of the eye, receives light that is out-of-focus. Here, we propose three mechanisms through which both retinas may receive focused light: (1) chromatic aberration produced by the lens may cause the focal points for longer and shorter wavelengths to fall near the distal and proximal retinas, respectively; (2) focused light from near and far objects may fall on the distal and proximal retinas, respectively; and (3) the eyes of scallops may be dynamic structures that change shape to determine which retina receives focused light. To test our hypotheses, we used optical coherence tomography (OCT), a method of near infrared optical depth-ranging, to acquire virtual cross-sections of live, intact eyes from the bay scallop Argopecten irradians Next, we used a custom-built ray tracing model to estimate the qualities of the images that fall on an eye's distal and proximal retinas as functions of the wavelengths of light entering the eye (400-700 nm), object distances (0.01-1 m), and the overall shape of the eye. When we assume 550 nm wavelength light and object distances greater than 0.01 m, our model predicts that the angular resolutions of the distal and proximal retinas are 2 degrees and 7 degrees , respectively. Our model also predicts that neither chromatic aberration nor differences in object distance lead to focused light falling on the distal and proximal retinas simultaneously. However, if scallops can manipulate the shapes of their eyes, perhaps through muscle contractions, we speculate that they may be able to influence the qualities of the images that fall on their proximal retinas and-to a lesser extent-those that fall on their distal retinas as well. PMID- 27549201 TI - Energetics of Sensing and Communication in Electric Fish: A Blessing and a Curse in the Anthropocene? AB - Weakly electric freshwater fish use self-generated electric fields to image their worlds and communicate in the darkness of night and turbid waters. This active sensory/communication modality evolved independently in the freshwaters of South America and Africa, where hundreds of electric fish species are broadly and abundantly distributed. The adaptive advantages of the sensory capacity to forage and communicate in visually-unfavorable environments and outside the detection of visually-guided predators likely contributed to the broad success of these clades across a variety of Afrotropical and neotropical habitats. Here we consider the potentially high and limiting metabolic costs of the active sensory and communication signals that define the gymnotiform weakly electric fish of South America. Recent evidence from two well-studied species suggests that the metabolic costs of electrogenesis can be quite high, sometimes exceeding one fourth of these fishes' daily energy budget. Supporting such an energetically expensive system has shaped a number of cellular, endocrine, and behavioral adaptations to restrain the metabolic costs of electrogenesis in general or in response to metabolic stress. Despite a suite of adaptations supporting electrogenesis, these weakly electric fish are vulnerable to metabolic stresses such as hypoxia and food restriction. In these conditions, fish reduce signal amplitude presumably as a function of absolute energy shortfall or as a proactive means to conserve energy. In either case, reducing signal amplitude compromises both sensory and communication performance. Such outcomes suggest that the higher metabolic cost of active sensing and communication in weakly electric fish compared with the sensory and communication systems in other neotropical fish might mean that weakly electric fish are disproportionately susceptible to harm from anthropogenic disturbances of neotropical aquatic habitats. Fully evaluating this possibility, however, will require broad comparative studies of metabolic energetics across the diverse clades of gymnotiform electric fish and in comparison to other nonelectric neotropical fishes. PMID- 27549202 TI - Environmental Adaptation, Phenotypic Plasticity, and Associative Learning in Insects: The Desert Locust as a Case Study. AB - The ability to learn and store information should be adapted to the environment in which animals operate to confer a selective advantage. Yet the relationship between learning, memory, and the environment is poorly understood, and further complicated by phenotypic plasticity caused by the very environment in which learning and memory need to operate. Many insect species show polyphenism, an extreme form of phenotypic plasticity, allowing them to occupy distinct environments by producing two or more alternative phenotypes. Yet how the learning and memories capabilities of these alternative phenotypes are adapted to their specific environments remains unknown for most polyphenic insect species. The desert locust can exist as one of two extreme phenotypes or phases, solitarious and gregarious. Recent studies of associative food-odor learning in this locust have shown that aversive but not appetitive learning differs between phases. Furthermore, switching from the solitarious to the gregarious phase (gregarization) prevents locusts acquiring new learned aversions, enabling them to convert an aversive memory formed in the solitarious phase to an appetitive one in the gregarious phase. This conversion provides a neuroecological mechanism that matches key changes in the behavioral environments of the two phases. These findings emphasize the importance of understanding the neural mechanisms that generate ecologically relevant behaviors and the interactions between different forms of behavioral plasticity. PMID- 27549203 TI - Exploring the prevalence and variance of cognitive impairment, pain, neuropsychiatric symptoms and ADL dependency among persons living in nursing homes; a cross-sectional study. AB - BACKGROUND: Earlier studies in nursing homes show a high prevalence of cognitive impairment, dependency in activities of daily living (ADL), pain, and neuropsychiatric symptoms among residents. The aim of this study was to explore the prevalence of the above among residents in a nationally representative sample of Swedish nursing homes, and to investigate whether pain and neuropsychiatric symptoms differ in relation to gender, cognitive function, ADL-capacity, type of nursing-home unit and length of stay. METHODS: Cross-sectional data from 188 randomly selected nursing homes were collected. A total of 4831 residents were assessed for cognitive and ADL function, pain and neuropsychiatric symptoms. Data were analysed using descriptive statistics and the chi-square test. RESULTS: The results show the following: the prevalence of cognitive impairment was 67 %, 56 % of residents were ADL-dependent, 48 % exhibited pain and 92 % exhibited neuropsychiatric symptoms. The prevalence of pain did not differ significantly between male and female residents, but pain was more prevalent among cognitively impaired and ADL-dependent residents. Pain prevalence was not significantly different between residents in special care units for people with dementia (SCU) and general units, or between shorter-and longer-stay residents. Furthermore, the prevalence of neuropsychiatric symptoms did not differ significantly between male and female residents, between ADL capacities or in relation to length of stay. However, residents with cognitive impairment and residents in SCUs had a significantly higher prevalence of neuropsychiatric symptoms than residents without cognitive impairment and residents in general units. CONCLUSIONS: The prevalence rates ascertained in this study could contribute to a greater understanding of the needs of nursing-home residents, and may provide nursing home staff and managers with trustworthy assessment scales and benchmark values for further quality assessment purposes, clinical development work and initiating future nursing assessments. PMID- 27549204 TI - Facile Synthesis of Boron-Doped rGO as Cathode Material for High Energy Li-O2 Batteries. AB - To improve the electrochemical performance of the high energy Li-O2 batteries, it is important to design and construct a suitable and effective oxygen-breathing cathode. Herein, a three-dimensional (3D) porous boron-doped reduction graphite oxide (B-rGO) material with a hierarchical structure has been prepared by a facile freeze-drying method. In this design, boric acid as the boron source helps to form the 3D porous structure, owing to its cross-linking and pore-forming function. This architecture facilitates the rapid oxygen diffusion and electrolyte penetration in the electrode. Meanwhile, the boron-oxygen functional groups linking to the carbon surface or edge serve as additional reaction sites to activate the ORR process. It is vital that boron atoms have been doped into the carbon lattices to greatly activate the electrons in the carbon pi system, which is beneficial for fast charge under large current densities. Density functional theory calculation demonstrates that B-rGO exhibits much stronger interactions with Li5O6 clusters, so that B-rGO more effectively activates Li-O bonds to decompose Li2O2 during charge than rGO does. With B-rGO as a catalytic substrate, the Li-O2 battery achieves a high discharge capacity and excellent rate capability. Moreover, catalysts could be added into the B-rGO substrate to further lower the overpotential and enhance the cycling performance in future. PMID- 27549205 TI - Hypoxia and its implications in rheumatoid arthritis. AB - Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process. PMID- 27549206 TI - The indirect association of job strain with long-term sickness absence through bullying: a mediation analysis using structural equation modeling. AB - BACKGROUND: In this longitudinal study the complex interplay between both job strain and bullying in relation to sickness absence was investigated. Following the "work environment hypothesis", which establishes several work characteristics as antecedents of bullying, we assumed that job strain, conceptualized by the Job Demand-Control model, has an indirect relation with long-term sickness absence through bullying. METHODS: The sample consisted of 2983 Belgian workers, aged 30 to 55 years, who participated in the Belstress III study. They completed a survey, including the Job Content Questionnaire and a bullying inventory, at baseline. Their sickness absence figures were registered during 1 year follow-up. Long-term sickness absence was defined as at least 15 consecutive days. A mediation analysis, using structural equation modeling, was performed to examine the indirect association of job strain through bullying with long-term sickness absence. The full structural model was adjusted for several possible confounders: age, gender, occupational group, educational level, company, smoking habits, alcohol use, body mass index, self-rated health, baseline long-term sickness absence and neuroticism. RESULTS: The results support the hypothesis: a significant indirect association of job strain with long-term sickness absence through bullying was observed, suggesting that bullying is an intermediate variable between job strain and long-term sickness absence. No evidence for the reversed pathway of an indirect association of bullying through job strain was found. CONCLUSIONS: Bullying was observed as a mediating variable in the relation between job strain and sickness absence. The results suggest that exposure to job strain may create circumstances in which a worker risks to become a target of bullying. Our findings are generally in line with the work environment hypothesis, which emphasizes the importance of organizational work factors in the origin of bullying. This study highlights that remodeling jobs to reduce job strain may be important in the prevention of bullying and subsequent sickness absence. PMID- 27549209 TI - Erratum to: Leishmania infantum-specific production of IFN-gamma and IL-10 in stimulated blood from dogs with clinical leishmaniosis. PMID- 27549208 TI - Motivation and incentive preferences of community health officers in Ghana: an economic behavioral experiment approach. AB - BACKGROUND: Health worker shortage in rural areas is one of the biggest problems of the health sector in Ghana and many developing countries. This may be due to fewer incentives and support systems available to attract and retain health workers at the rural level. This study explored the willingness of community health officers (CHOs) to accept and hold rural and community job postings in Ghana. METHODS: A discrete choice experiment was used to estimate the motivation and incentive preferences of CHOs in Ghana. All CHOs working in three Health and Demographic Surveillance System sites in Ghana, 200 in total, were interviewed between December 2012 and January 2013. Respondents were asked to choose from choice sets of job preferences. Four mixed logit models were used for the estimation. The first model considered (a) only the main effect. The other models included interaction terms for (b) gender, (c) number of children under 5 in the household, and (d) years worked at the same community. Moreover, a choice probability simulation was performed. RESULTS: Mixed logit analyses of the data project a shorter time frame before study leave as the most important motivation for most CHOs (beta 2.03; 95 % CI 1.69 to 2.36). This is also confirmed by the largest simulated choice probability (29.1 %). The interaction effect of the number of children was significant for education allowance for children (beta 0.58; 95 % CI 0.24 to 0.93), salary increase (beta 0.35; 95 % CI 0.03 to 0.67), and housing provision (beta 0.16; 95 % CI -0.02 to 0.60). Male CHOs had a high affinity for early opportunity to go on study leave (beta 0.78; 95 % CI -0.06 to 1.62). CHOs who had worked at the same place for a long time greatly valued salary increase (beta 0.28; 95 % CI 0.09 to 0.47). CONCLUSIONS: To reduce health worker shortage in rural settings, policymakers could provide "needs-specific" motivational packages. They should include career development opportunities such as shorter period of work before study leave and financial policy in the form of salary increase to recruit and retain them. PMID- 27549210 TI - Subinhibitory concentrations of phloretin repress the virulence of Salmonella typhimurium and protect against Salmonella typhimurium infection. AB - Phloretin, a natural component of many fruits, exhibits anti-virulence effects and provides a new alternative to counter bacterial infection. The aim of this study was to determine the effect of subinhibitory concentrations of phloretin on the virulence of Salmonella typhimurium. At concentrations where growth of Salmonella was not inhibited, phloretin significantly inhibited bacteria biofilm formation and motility. Subinhibitory concentrations of phloretin repressed eight genes involved in the Salmonella pathogenicity island 1 and 3 genes involved in flagella production. Furthermore, subinhibitory concentrations of phloretin inhibited the adhesion and invasion of Salmonella in IEC-6 cells and reduced the LDH levels of S. typhimurium-infected IEC-6 cells. Additionally, phloretin significantly decreased the cecum bacterial loads of the mice infected with live S. typhimurium containing subinhibitory concentrations of phloretin by gavage. These results suggested that subinhibitory concentrations of phloretin attenuate the virulence of S. typhimurium and protect against S. typhimurium infection. PMID- 27549211 TI - Rhl quorum sensing affects the virulence potential of Pseudomonas aeruginosa in an experimental urinary tract infection. AB - Pseudomonas aeruginosa quorum sensing systems (QSS) las, rhl and PQS play a significant role in pathogenicity. Although multiple studies have explored the role of the las QSS in various types of infections, including urinary tract infections (UTIs), the role of the rhl QSS is still poorly understood. In this study, an attempt was made to explore the role of the rhl QSS in the pathogenesis of UTI. The wild-type strain P. aeruginosa PAO1 and its isogenic rhl QSS mutant strains, PDO-100 and PDO-111, were used. Strains were studied for the expression of extra-cellular virulence factors and the ability to induce experimental UTI in a mouse model. Evaluation was based on in vitro estimation of virulence factors (elastase, protease, rhamnolipid) and in vivo bacteriological and histopathological analysis of renal and bladder tissue. The cytokine levels were determined in the renal tissue of infected mice. Wild-type PAO1 showed the highest level of virulence traits. The tissue bacteriology and histopathology were indicative of establishment of UTI. The level of inflammatory cytokines was consistent with the bacteriology and pathology results. The rhl QSS mutant strains showed significantly reduced pathogenicity. On supplementation with C4 homoserine lactone, strain PDO-100 showed a significant increase in pathogenicity. The results indicate that the rhl QSS affects the virulence potential of P. aeruginosa and that, despite the presence of the las QSS, mutant strains exhibited reduced pathology. Therefore, the rhl QSS may be exploited in more detail for future drug intervention tactics. PMID- 27549212 TI - Comparison of the clinical performance of i-gel, LMA Supreme and LMA ProSeal in elective surgery. AB - INTRODUCTION: The LMA SupremeTM, i-gel(r) and LMA ProSealTM are second-generation supraglottic airway devices. We tested the hypothesis that these devices differ in performance when used for spontaneous ventilation during anaesthesia. METHODS: 150 patients who underwent general anaesthesia for elective surgery were randomly allocated into three groups. Data was collected on oropharyngeal leak pressures, ease and duration of device insertion, ease of gastric tube insertion, and airway safety. RESULTS: Leak pressure, our primary outcome measure, was found to be higher for the i-gel than the Supreme and ProSeal (mean +/- standard error of the mean: 27.31 +/- 0.92 cmH2O, 23.60 +/- 0.70 cmH2O and 24.44 +/- 0.70 cmH2O, respectively; p = 0.003). Devices were inserted on the first attempt for 90%, 82% and 72% of patients in the i-gel, Supreme and ProSeal groups, respectively (p = 0.105); mean device placement times were 23.58 seconds, 25.10 seconds and 26.34 seconds, respectively (p = 0.477). Gastric tubes were inserted on the first attempt in 100% of patients in the Supreme group, and 94% of patients in the i gel and ProSeal groups (p = 0.100). There was blood staining on removal in 9 (18%) patients in each of the Supreme and ProSeal groups, with none in the i-gel group (p = 0.007). The incidence of postoperative sore throat, dysphagia and hoarseness was lowest for the i-gel. CONCLUSION: The three devices were comparable in terms of ease and duration of placement, but the i-gel had higher initial oropharyngeal leak pressure and lower airway morbidity compared with the ProSeal and Supreme. PMID- 27549213 TI - Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis. AB - Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93-80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage. PMID- 27549214 TI - Impact of surgical timing on the outcome of anterior cruciate ligament reconstruction. AB - PURPOSE: The purpose of the present study is the comparison of acute ACL reconstruction with or without meniscus repair within 48 h after injury and a delayed surgery during the inflammation-free interval. It was hypothesized that acute ACL reconstruction results in inferior patient reported outcomes and higher frequency of range of motion deficits. METHODS: The effect of acute (within 48 h) and delayed (during the inflammation-free interval) ACL surgery was prospectively studied on 160 consecutive patients with ACL injury between January 2010 and December 2011. Subgroup analyses were performed to evaluate patients with an additional meniscus repair separately from isolated ACL surgeries. During the study period, partial meniscectomies were recorded to evaluate time dependent meniscus reparability. Patient reported outcomes, objective IKDC and manual stability measurements were documented during the 24-month follow-up period. The Pearson Chi-squared test was used to evaluate objective outcome measures. The Mann-Whitney U test was performed to analyse the results of patient reported outcomes. Statistical significance was set at p < 0.05. RESULTS: For patients who underwent isolated ACL reconstruction, no statistical significant difference was observed at any time point regarding objective and subjective outcome measures. Significantly fewer patients who underwent acute combined ACL reconstruction and meniscus repair had an extension deficit between 3 degrees and 5 degrees at 12 months following surgery (3.7 vs. 22.2 %, p < 0.05). No difference regarding cyclops removal, re-injury of ACL or meniscus was found between the two surgical timing groups. Further, surgical timing did not influence the reparability of the meniscus. CONCLUSION: An acute ACL reconstruction within 48 h is preferable in highly active patients or competitive athletes. LEVEL OF EVIDENCE: Prospective cohort study, Level II. PMID- 27549215 TI - The sex-dependent role of the glucocorticoid receptor in depression: variations in the NR3C1 gene are associated with major depressive disorder in women but not in men. AB - Genetic variations in the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) have been associated with maladaptive stress responses and major depressive disorder (MDD). In a case-control study design, we examined whether single nucleotide polymorphisms (SNPs) and haploid genotype (haplotype) associations of MR gene NR3C2, GR gene NR3C1 and genes of GR chaperone molecules FK506 binding protein 5 (FKBP5) and corticotrophin-releasing hormone receptor 1 (CRHR1) differed between healthy subjects (n = 634) and inpatients with major depressive disorder (n = 412). All analyses were conducted for women and men separately. After conservative correction of Type-I-error to obtain reliable p values, one SNP in the NR3C1 gene, namely rs6195, showed a significant association with the presence of a major depression (p = 0.048) in females. In contrast, NR3C2, FKBP5 and CRHR1 polymorphisms were not significantly associated with MDD. No haplotype effects could be identified. Our results support the notion of an association between variants of GR-related genes in women and the pathophysiology of depression: females suffering from MDD showed a more than three times higher frequency of the T/C polymorphism compared to controls, which thus seems to increase the vulnerability to depression in females. PMID- 27549217 TI - Training demands on clerk burnout: determining whether achievement goal motivation orientations matter. AB - BACKGROUND: In the education field, learning experiences are considered learners' properties and are viewed as a key determinant in explaining learners' learning processes, especially for training novices such as clerks with varying levels of commitment to the medical profession. This study explored whether clerks' achievement goal motivation orientations might buffer the negative well-being to a certain extent, considering their training demands during clinical training. METHODS: Ninety-four clerks at a tertiary medical center were longitudinally traced during their 2-year clerkship spanning from September 2013 to April 2015. Web-based, validated, structured, self-administered questionnaires were used to evaluate the clerks' properties of achievement goal motivation orientation and personal background at the beginning of the clerkship. Regular surveys were conducted to evaluate their perceptions of training demands and burnout at each specialty rotation. Overall, 2230 responses were analyzed, and linear mixed effects models were used to examine the repeated measures of the clerks. RESULTS: The results revealed that higher perceived psychological and physical demands of training were related to higher perceived burnout during the 2-year clerkship. Although both the clerks' task and ego orientations were related to reduced burnout (direct effects), only task orientation was indicated to exert a buffering effect on their perception of physical demands on burnout in the 1st year of the clerkship. CONCLUSIONS: Considering the negative effects of training demands (psychological and physical), we observed a limited effect of the task achievement motivation orientation of medical students; therefore, additional studies might focus on strategies to facilitate medical students in clerkships in addressing both the psychological and physical demands inherent in training workplaces to improve their learning experience and well-being. PMID- 27549216 TI - Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder. AB - Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders. PMID- 27549218 TI - Molecular cloning and characterization of a flavonoid-O-methyltransferase with broad substrate specificity and regioselectivity from Citrus depressa. AB - BACKGROUND: Flavonoids are secondary metabolites that play significant roles in plant cells. In particular, polymethoxy flavonoids (PMFs), including nobiletin, have been reported to exhibit various health-supporting properties such as anticancer, anti-inflammatory, and anti-pathogenic properties. However, it is difficult to utilize PMFs for medicinal and dietary use because plant cells contain small amounts of these compounds. Biosynthesis of PMFs in plant cells is carried out by the methylation of hydroxyl groups of flavonoids by O methyltransferases (FOMT), and many kinds of FOMTs with different levels of substrate specificity and regioselectivity are cooperatively involved in this biosynthesis. RESULTS: In this study, we isolated five genes encoding FOMT (CdFOMT1, 3, 4, 5, and 6) from Citrus depressa, which is known to accumulate nobiletin in the peels of its fruits. The genes encoded Mg(2+)-independent O methyltransferases and showed high amino acid sequence similarity (60-95 %) with higher plant flavonoid O-methyltransferases. One of these genes is CdFOMT5, which was successfully expressed as a soluble homodimer enzyme in Escherichia coli. The molecular mass of the recombinant CdFOMT5 subunit was 42.0 kDa including a 6* histidine tag. The enzyme exhibited O-methyltransferase activity for quercetin, naringenin, (-)-epicatechin, and equol using S-adenosyl-L-methionine (SAM) as a methyl donor, and its optimal pH and temperature were pH 7.0 and 45 degrees C, respectively. The recombinant CdFOMT5 demonstrated methylation activity for the 3 , 5-, 6-, and 7-hydroxyl groups of flavones, and 3,3',5,7-tetra-O-methylated quercetin was synthesized from quercetin as a final product of the whole cell reaction system. Thus, CdFOMT5 is a O-methyltransferase possessing a broad range of substrate specificity and regioselectivity for flavonoids. CONCLUSIONS: Five FOMT genes were isolated from C. depressa, and their nucleotide sequences were determined. CdFOMT5 was successfully expressed in E. coli cells, and the enzymatic properties of the recombinant protein were characterized. Recombinant CdFOMT5 indicated O-methyltransferase activity for many flavonoids and a broad regioselectivity for quercetin as a substrate. Whole-cell biocatalysis using CdFOMT5 expressed in E. coli cells was performed using quercetin as a substrate, and 3,3',5,7-tetramethylated quercetin was obtained as the final product. PMID- 27549221 TI - A highly aluminum-doped beta-isomer Keggin-type tungstoaluminate. AB - A trialuminum-substituted beta-isomer Keggin-type tungstoaluminate was synthesized and characterized, in which the pure metal-oxygen cluster [AlW8.5Al0.5{Al(OH2)}3(OH)3O34](6.5-) consists of three kinds of aluminum sites: the central Al(1), the doped Al(5), and the substituted Al(2) and Al(3) centers. PMID- 27549219 TI - The prevalence of human papillomavirus infections and associated risk factors in men-who-have-sex-with-men in Cape Town, South Africa. AB - BACKGROUND: We investigated the prevalence of human papillomavirus (HPV) infection and associated behavioural risk factors in men-who-have-sex-with-men (MSM) attending a clinical service in Cape Town, South Africa. METHODS: MSM were enrolled at the Ivan Toms Centre for Men's Health in Cape Town. A psychosocial and sexual behavioral risk questionnaire was completed for each participant and urine, oro-pharyngeal and anal swabs were collected for HPV testing using the Linear Array HPV Genotyping Test. Logistic regression analyses were performed to determine sexual risk factors associated with HPV infection at the three anatomical sites. RESULTS: The median age of all 200 participants was 32 years (IQR 26-39.5), of which 31.0 % were black, 31.5 % mixed race/coloured and 35.5 % white. The majority of the participants (73.0 %) had completed high school, 42.0 % had a tertiary level qualification and 69.0 % were employed. HPV genotypes were detected in 72.8 % [95 % CI: 65.9-79.0 %], 11.5 % [95 % CI: 7.4-16.8 %] and 15.3 % [95 % CI: 10.5-21.2 %] of anal, oro-pharyngeal and urine specimens, respectively. Prevalence of high-risk (HR)-HPV types was 57.6 % [95 % CI: 50.3 64.7 %] in anal samples, 7.5 % [95 % CI: 4.3-12.1 %] in oro-pharyngeal samples and 7.9 % [95 % CI: 4.5-12.7 %] in urine, with HPV-16 being the most common HR HPV type detected at all sites. HPV-6/11/16/18 was detected in 40.3 % [95 % CI: 33.3-47.6 %], 4.5 % [95 % CI: 2.1-8.4 %] and 3.2 % [95 % CI: 1.2-6.8 %] of anal, oro-pharyngeal and urine samples, respectively. Multiple HPV types were more common in the anal canal of MSM while single HPV types constituted the majority of HPV infections in the oropharynx and urine. Among the 88 MSM (44.0 %) that were HIV positive, 91.8 % [95 % CI: 83.8-96.6 %] had an anal HPV infection, 81.2 % [95 % CI: 71.2-88.8 %] had anal HR-HPV and 85.9 % [95 % CI: 76.6-92.5 %] had multiple anal HPV types. Having sex with men only, engaging in group sex in lifetime, living with HIV and practising receptive anal intercourse were the only factors independently associated with having any anal HPV infection. CONCLUSIONS: Anal HPV infections were common among MSM in Cape Town with the highest HPV burden among HIV co-infected MSM, men who have sex with men only and those that practiced receptive anal intercourse. Behavioural intervention strategies and the possible roll-out of HPV vaccines among all boys are urgently needed to address the high prevalence of HPV and HIV co-infections among MSM in South Africa. PMID- 27549220 TI - Dietary patterns associated with body mass index (BMI) and lifestyle in Mexican adolescents. AB - BACKGROUND: The objetive in this study is to determine the relationship between dietary patterns, BMI, type 2 diabetes mellitus family history (T2DMFH) and some lifestyle variables such as smoking and skipping breakfast in a Mexican adolescent population. METHODS: Cross-sectional, observational, analytical study.Subjetcts: 14-16 years old male and female adolescents (n 373). A previously validated food frequency questionnaire (FFQ) was used and dietary patterns were derived using principal component analysis (PCA). Scores for dietary patterns were categorized by tertiles. RESULTS: Three major dietary patterns that explained 47 % of variance were found: westernized, high in protein/fat and prudent pattern. Subjects at the highest tertile of prudent pattern had lower BMI. And was also associated with less T2DMFH and less smoking habit when compared with the lowest tertile. We found a positive correlation between BMI and high scores for westernized and high in protein/fat pattern CONCLUSIONS: Dietary patterns of adolescents are a public health concern because there is a direct association between inadequate diet at this early age and obesity. PMID- 27549222 TI - The dorsal nerve of the clitoris in relation to urinary incontinence sling procedures. AB - INTRODUCTION AND HYPOTHESIS: To avoid injury to the perineal branches of the pudendal nerve during urinary incontinence sling procedures, a thorough knowledge of the course of these nerve branches is essential. The dorsal nerve of the clitoris (DNC) may be at risk when performing the retropubic (tension-free vaginal tape) procedure as well as the inside-out and outside-in transobturator tape procedures. The purpose of this study was to identify the anatomical relationships of the DNC to the tapes placed during the procedures mentioned and to determine the influence of body variations. METHODS: In this cadaveric study, the body mass index (cBMI) of unembalmed cadavers was determined. Suburethral tape procedures were performed by a registered urologist and gynecologist on a sample of 15 female cadavers; six retropubic, seven inside-out and nine outside in transobturator tapes were inserted. After embalmment, dissections were performed and the distances between the DNC and the tapes measured. RESULTS: In general the trajectory of the outside-in tape was closer to the DNC than that of the other tapes. cBMI was weakly and nonsignificantly correlated with the distance between the trajectory of the tape and the DNC for the inside-out tape and the tension-free vaginal tape, but not for the outside-in tape. CONCLUSIONS: The findings suggest that the DNC is less likely to be injured during the inside out tape procedure than during the outside-in procedure, regardless of BMI. Future studies on larger samples are desirable to confirm these findings. PMID- 27549223 TI - Complications and reoperations after laparoscopic sacrocolpopexy with a mean follow-up of 4 years. AB - INTRODUCTION AND HYPOTHESIS: There is a lack of knowledge concerning long-term reoperation and complications after laparoscopic sacrocolpopexy (LSCP). We analyzed the rates and indications and potential risk factors for reoperation after LSCP in a large series of consecutive patients. METHODS: This was a single center, retrospective study including all patients who underwent LSCP between 2003 and 2013. Data regarding pelvic organ prolapse (POP), surgical modalities and perioperative complications were collected. Patients were then contacted by telephone or postal letter in 2014. The main outcome criteria were grade III Dindo classification complications: reoperation for POP recurrence, mesh complications, and urinary incontinence (UI). RESULTS: Between January 2003 and December 2013, a total of 464 consecutive patients (mean age, 59 years) underwent LSCP. Almost all (99.1 %) patients presented with POP >= grade 3 (POP-Q classification). Long-term evaluations were completed for 391 (84.1 %) patients. The median follow-up was 53.5 +/- 28.2 months. The global reoperation rate was 12.5 %. The main reoperation indications were UI-related surgery in 21 patients (5.5 %), POP recurrence surgery in 20 patients (5.1 %), and mesh-related surgery in 11 patients (2.8 %). Multivariate analysis showed that older age at the time of initial surgery and concomitant subtotal hysterectomy were significant protective factors against global reoperation (HR = 0.606, CI 95 % [0.451-0.815] and 0.367, CI 95 % [0.193-0.698] respectively) and reduced the risk of POP recurrence surgery. CONCLUSION: Prolapse recurrence and mesh-related surgery occurred in 5.1 and 2.8 % of patients respectively, 4 years after laparoscopic sacrocolpopexy. Age and concomitant subtotal hysterectomy could play a role in the incidence of long-term reoperation. PMID- 27549224 TI - Correlation of bladder wall thickness and treatment success in types of urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: The aim of the study was to investigate the correlation between mean bladder wall thickness (BWT) and treatment success in patients diagnosed with urinary incontinence, based on urodynamic test results. METHODS: In this prospective study, patient urinary incontinence type was identified using urodynamic tests. Patients (N = 125) were categorized into three groups: urodynamic stress incontinence (SUI), detrusor over-activity (DO) and mixed urinary incontinence. Measurements from the bladder dome, anterior wall and trigone were averaged to calculate BWT. Student's t test and Mann-Whitney U test were used to compare pre-treatment BWT. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for BWT to predict treatment success. RESULTS: Mean pre-treatment BWT significantly differed between success and non-success groups for each urinary incontinence type (p value for the SUI, DO and MUI groups was 0.043, 0.001 and 0.002 respectively). Using ROC curves to anticipate the treatment success, a threshold was calculated for mean pre-treatment BWT; 5.05 mm for SUI (sensitivity 74 %, specificity 66 %, positive predictive value [PPV] 85 %, negative predictive value [NPV] 50 %), 4.98 mm for DO (sensitivity 73 %, specificity 92 %, PPV 95 %, NPV 63 %) and 5.31 mm for mixed type (sensitivity 88 %, specificity 73 %, PPV 79 %, NPV 85 %). CONCLUSIONS: The study results suggest a significant relationship between the pre-treatment BWT and the success of urinary incontinence treatment. The mean BWT may be used as a benchmark in assessing the responsiveness to treatment of urinary incontinence types. PMID- 27549225 TI - Transvaginal mesh: a historical review and update of the current state of affairs in the United States. AB - INTRODUCTION: Transvaginal mesh usage has been at the forefront of popular media and academic debate for the past 10 years. Several US Food and Drug Administration (FDA) communications, society statements, and research articles have been written in an attempt to define and articulate the classification system, safety data, and efficacy of this approach to transvaginal surgery. In this review, we explore the history of transvaginal mesh surgery for pelvic organ prolapse (POP), review FDA and society statements, and research current practice in the United States. METHODS: We searched the English language literature using PubMed for articles related to safety and monitoring of transvaginal mesh and reviewed all FDA publication and notices and gynecology and urogynecology society statements on its use in the United States. We then reviewed 22 articles and grouped them into several sections. RESULTS: Mesh used to augment transvaginal repair of POP was introduced in the United States in 2005 without clinical safety and efficacy data. In the subsequent years of use, both major and minor complications were increasingly reported, leading to several FDA notifications and warnings. The type of mesh used, reporting and classifications systems, and provider usage has varied widely over time. CONCLUSION: We present a historical review of transvaginal mesh use for pelvic organ prolapse in the United States from 2005 to 2016. There continues to be heated debate among practitioners about balancing the efficacy of mesh use to decrease recurrent prolapse and complications. Research into safety and efficacy, along with tighter FDA regulations, is ongoing. PMID- 27549226 TI - Impact of MPH programs: contributing to health system strengthening in low- and middle-income countries? AB - BACKGROUND: The "health workforce" crisis has led to an increased interest in health professional education, including MPH programs. Recently, it was questioned whether training of mid- to higher level cadres in public health prepared graduates with competencies to strengthen health systems in low- and middle-income countries. Measuring educational impact has been notoriously difficult; therefore, innovative methods for measuring the outcome and impact of MPH programs were sought. Impact was conceptualized as "impact on workplace" and "impact on society," which entailed studying how these competencies were enacted and to what effect within the context of the graduates' workplaces, as well as on societal health. METHODS: This is part of a larger six-country mixed method study; in this paper, the focus is on the qualitative findings of two English language programs, one a distance MPH program offered from South Africa, the other a residential program in the Netherlands. Both offer MPH training to students from a diversity of countries. In-depth interviews were conducted with 10 graduates (per program), working in low- and middle-income health systems, their peers, and their supervisors. RESULTS: Impact on the workplace was reported as considerable by graduates and peers as well as supervisors and included changes in management and leadership: promotion to a leadership position as well as expanded or revitalized management roles were reported by many participants. The development of leadership capacity was highly valued amongst many graduates, and this capacity was cited by a number of supervisors and peers. Wider impact in the workplace took the form of introducing workplace innovations such as setting up an AIDS and addiction research center and research involvement; teaching and training, advocacy, and community engagement were other ways in which graduates' influence reached a wider target grouping. Beyond the workplace, an intersectoral approach, national reach through policy advisory roles to Ministries of Health, policy development, and capacity building, was reported. Work conditions and context influenced conduciveness for innovation and the extent to which graduates were able to have effect. Self-selection of graduates and their role in selecting peers and supervisors may have resulted in some bias, some graduates could not be traced, and social acceptability bias may have influenced findings. CONCLUSIONS: There was considerable impact at many levels; graduates were perceived to be able to contribute significantly to their workplaces and often had influence at the national level. Much of the impact described was in line with public health educational aims. The qualitative method study revealed more in-depth understanding of graduates' impact as well as their career pathways. PMID- 27549227 TI - Prevention and management of vision loss relating to facial filler injections. AB - INTRODUCTION: With the increased use of filler and fat injections for aesthetic purposes, there has been a corresponding increase in the incidence of complications. Vision loss as an uncommon but devastating vascular side effect of filler injections was the focus of this paper. METHODS: A review committee, consisting of plastic surgeons, aesthetic medical practitioners, ophthalmologists and dermatologists from Singapore, was convened by the Society of Aesthetic Medicine (Singapore) to review and recommend methods for the prevention and management of vision loss secondary to filler injections. RESULTS: The committee agreed that prevention through proper understanding of facial anatomy and good injection techniques was of foremost importance. The committee acknowledged that there is currently no standard management for these cases. Based on existing knowledge, injectors may follow a proposed course of action, which can be divided into immediate, definitive and supportive. The goals were to reduce intraocular pressure, dislodge the embolus to a more peripheral location, remove or reverse central ischaemia, preserve residual retinal function, and prevent the deterioration of vision. Dissolving a hyaluronic acid embolus remains a controversial option. It is proposed that injectors must be trained to recognise symptoms, institute immediate actions and refer patients without delay to dedicated specialists for definitive and supportive management. CONCLUSIONS: Steps to prevent and manage vision loss based on current evidence and best clinical practices are outlined in this paper. Empirical referral to any emergency department or untrained doctors may lead to inordinate delays and poor outcomes for the affected eye. PMID- 27549228 TI - Performance of stented biological valves for right ventricular outflow tract reconstruction. AB - OBJECTIVES: This retrospective single-centre review presents mid- and long-term results of stented biological valves (SBVs) in the pulmonary position. METHODS: Fifty-two SBVs (17 Carpentier-Edwards Supraannular; 13 Carpentier-Edwards Perimount; 12 St. Jude Medical Trifecta; 4 Sorin Mitroflow; 4 Sorin Soprano; 2 Sorin More) were implanted between 2000 and 2015. The median valve size, patient age and weight were 23 mm (range 19-27), 22.8 years (range 5-77) and 62.0 kg (range 14-110), respectively. The main cardiac diagnosis was tetralogy of Fallot in 26 patients (50%). Forty-four patients (85%) had previous cardiac surgery; 12 patients (23%) had previous conduit or biological valve replacement. Valve degeneration was defined as a valvular peak pressure gradient >50 mmHg or pulmonary valve regurgitation more than moderate. RESULTS: The mean follow-up was 7.9 +/- 5.5 years. Two patients died after 5.8 and 6.1 years of causes not related to SBVs. Eleven SBVs (21%) had to be replaced surgically (n = 6) or interventionally (n = 5) after 9.0 +/- 4.1 years due to valve degeneration (n = 8), endocarditis (n = 2) or right ventricular dysfunction (n = 1). The rates of freedom from valve replacement were 100%, 92% [95% confidence interval (CI) 79 97], 81% (CI 64-91) and 60% (CI 40-78) after 1, 5, 10 and 15 years, respectively. Successful interventional valve-in-valve implantation resulted in 100% freedom from surgical valve replacement in all patients older than 19.1 years. Multivariate analysis identified patient age <19.1 years (P = 0.007) as a risk factor for earlier valve degeneration. CONCLUSIONS: SBVs in the pulmonary position showed encouraging long-term results in mature patients. The design of SBVs enables interventional valve implantation, postponing the need for reoperation. PMID- 27549229 TI - Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury. AB - Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA) pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor beta (RXRbeta), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRbeta, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ MSCs + T3 (p <= 0.05). The same trend was also resulted for the levels of TNF alpha and IL-6 at four days after ischemia (p <= 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines. PMID- 27549230 TI - SHIVA - a web application for drug resistance and tropism testing in HIV. AB - BACKGROUND: Drug resistance testing is mandatory in antiretroviral therapy in human immunodeficiency virus (HIV) infected patients for successful treatment. The emergence of resistances against antiretroviral agents remains the major obstacle in inhibition of viral replication and thus to control infection. Due to the high mutation rate the virus is able to adapt rapidly under drug pressure leading to the evolution of resistant variants and finally to therapy failure. RESULTS: We developed a web service for drug resistance prediction of commonly used drugs in antiretroviral therapy, i.e., protease inhibitors (PIs), reverse transcriptase inhibitors (NRTIs and NNRTIs), and integrase inhibitors (INIs), but also for the novel drug class of maturation inhibitors. Furthermore, co-receptor tropism (CCR5 or CXCR4) can be predicted as well, which is essential for treatment with entry inhibitors, such as Maraviroc. Currently, SHIVA provides 24 prediction models for several drug classes. SHIVA can be used with single RNA/DNA or amino acid sequences, but also with large amounts of next-generation sequencing data and allows prediction of a user specified selection of drugs simultaneously. Prediction results are provided as clinical reports which are sent via email to the user. CONCLUSIONS: SHIVA represents a novel high performing alternative for hitherto developed drug resistance testing approaches able to process data derived from next-generation sequencing technologies. SHIVA is publicly available via a user-friendly web interface. PMID- 27549231 TI - Depth-dependence and monthly variability of charophyte biomass production: consequences for the precipitation of calcium carbonate in a shallow Chara-lake. AB - The month-to-month variability of biomass and CaCO3 precipitation by dense charophyte beds was studied in a shallow Chara-lake at two depths, 1 and 3 m. Charophyte dry weights (d.w.), the percentage contribution of calcium carbonate to the dry weight and the precipitation of CaCO3 per 1 m2 were analysed from May to October 2011. Physical-chemical parameters of water were also measured for the same sample locations. The mean dry weight and calcium carbonate precipitation were significantly higher at 1 m than at 3 m. The highest measured charophyte dry weight (exceeding 2000 g m-2) was noted at 1 m depth in September, and the highest CaCO3 content in the d.w. (exceeding 80 % of d.w.) was observed at 3 m depth in August. The highest CaCO3 precipitation per 1 m2 exceeded 1695 g at 1 m depth in August. Significant differences in photosynthetically active radiation (PAR) were found between 1 and 3 m depths; there were no significant differences between depths for other water properties. At both sampling depths, there were distinct correlations between the d.w., CaCO3 content and precipitation and water properties. In addition to PAR, the water temperature and magnesium and calcium ion concentrations were among the most significant determinants of CaCO3 content and d.w. The results show that light availability seems to be the major factor in determining charophyte biomass in a typical, undisturbed Chara-lake. The study results are discussed in light of the role of charophyte vegetation in whole ecosystem functioning, with a particular focus on sedimentary processes and the biogeochemical cycle within the littoral zone. PMID- 27549232 TI - Bioavailability evaluation, uptake of heavy metals and potential health risks via dietary exposure in urban-industrial areas. AB - A verity of human activities i.e. urbanization and industrialization have been resulted serious environmental contaminations by heavy metals in all over the world. The settlement of populations in urban and nearby industrial areas for economic development has significant share in their exposure to these metallic contaminants. Depending on the nature and type of the pollutants, targeted urban industrial environments can have harmful and chronic health risk impacts on exposed local inhabitants and may require detoxification, healing and remedial therapy. Consequently, environmental monitoring as well as human health risk assessments of urban environments under industrial influence are key dominant features. We believe this work will provide new insights into the studies of metals exposure and associated health risks in emerging industrials cities of developing countries. Present study aimed to study the bioavailability of metals, quantify the changeability in soil and vegetable metal concentrations and estimation of human health risks via dietary exposure, focusing on urban industrial environment. Soil and vegetable samples were collected in six random sites within the urban, periurban and industrial areas and analyzed for metal concentrations. In addition, risk assessment model proposed by US-EPA was employed to estimate the potential health risk of heavy metals via dietary intake. Results indicated that the heavy metal concentrations were noteworthy in periurban and urban-industrial areas. However, contamination levels varied with the type of vegetable, and the point source pollution such as traffic, urban wastes and industrial effluent. According to the estimated THQ and HI values for non-carcinogenic risk, little or no negative impact of heavy metals was observed on local inhabitants. However, the concentrations of Cr, Cd, Pb and Ni were nearly closed to the permissible limits described by US-EPA in urban-industrial areas. Conclusively, some efficient remedial strategies should be focus to overcome the increasing levels of Cr, Cd, Pb and Ni in this study area to protect the health of local inhabitants. PMID- 27549234 TI - Survey and research frame for ground sediment. PMID- 27549233 TI - Catalase and ascorbate peroxidase-representative H2O2-detoxifying heme enzymes in plants. AB - Plants have to counteract unavoidable stress-caused anomalies such as oxidative stress to sustain their lives and serve heterotrophic organisms including humans. Among major enzymatic antioxidants, catalase (CAT; EC 1.11.1.6) and ascorbate peroxidase (APX; EC 1.11.1.11) are representative heme enzymes meant for metabolizing stress-provoked reactive oxygen species (ROS; such as H2O2) and controlling their potential impacts on cellular metabolism and functions. CAT mainly occurs in peroxisomes and catalyzes the dismutation reaction without requiring any reductant; whereas, APX has a higher affinity for H2O2 and utilizes ascorbate (AsA) as specific electron donor for the reduction of H2O2 into H2O in organelles including chloroplasts, cytosol, mitochondria, and peroxisomes. Literature is extensive on the glutathione-associated H2O2-metabolizing systems in plants. However, discussion is meager or scattered in the literature available on the biochemical and genomic characterization as well as techniques for the assays of CAT and APX and their modulation in plants under abiotic stresses. This paper aims (a) to introduce oxidative stress-causative factors and highlights their relationship with abiotic stresses in plants; (b) to overview structure, occurrence, and significance of CAT and APX in plants; PMID- 27549236 TI - Erratum to: Concentrations and identification of culturable airborne fungi in underground stations of the Seoul metro. PMID- 27549235 TI - Tracing lead contamination in foods in the city of Kolkata, India. AB - Lead isotopic ratios (LIR) of eight common food items, street dust, coal, diesel, sediments, lead ore and rainwater from India have been reported for the first time in this paper. This study characterized the source and extent of lead pollution in the different foodstuff consumed in Kolkata, a major metropolis of eastern India. The atmospheric lead input to the food items, sold openly in busy roadside markets of the city, has been quantified. The mean 207/206 and 208/206 LIRs of the eight food items ranged from 0.8847 to 0.8924 and 2.145 to 2.167, respectively. Diesel had the highest mean 207/206 and 208/206 values of 0.9015 and 2.1869, respectively, apart from the lead ore. The food items had a mean lead concentration between 3.78 and 43.35 mg kg-1. The two ratio scatter plots of all the different environmental matrices were spread linearly between the uncontaminated Ichapur sediment and diesel. The 207/206 LIRs of the coal with a mean of 0.8777 did not fall in the linear trend, while the street dust and food samples overlapped strongly. The rainwater sample had a 207/206 LIR of 0.9007. Contaminated sediments in Dhapa, the repository of the city's municipal garbage, had a mean 207/206 LIR of 0.8658. The corresponding value obtained from the sewage-fed vegetable grown there was 0.8058. The present study indicated that diesel was one of the main contributor to Pb pollution. The atmospheric lead contribution to the food items was in the range of 68.48-86.66 %. PMID- 27549237 TI - Quality, Freedom and Equity: the Proposition of Educational Management in China. PMID- 27549238 TI - Assessment of arsenic in colostrum and cord serum and risk exposure to neonates from an island population in China. AB - Arsenic (As) has been proven to be highly toxic to humans, but limited attention has focused on exposure levels and potential risks to mother-neonate pairs of coastal populations. This study was conducted by examining the As concentration in colostrum and umbilical cord serum collected from 106 mother-neonate pairs living on Shengsi Island, facing the Yangtze River estuary and Hangzhou Bay in China. Average concentrations of total As in colostrum and cord serum were 18.51 +/- 7.00 and 19.83 +/- 10.50 MUg L-1. One-way ANOVA analysis showed delivered ages and source of drinking water played significant roles in influencing the maternal exposure patterns. Correlation analysis indicated a significantly positive association between As concentrations in colostrum and cord serum. Multivariable linear regression models adjusted for other confounders clarified the dose-response relationship with a coefficient value of 0.23 and a 95 % confidence interval of (0.006, 0.492); p < 0.05. The calculated daily intake of total As for neonates through breastfeeding was in the range from 0.413 to 3.65 MUg kg-1 body weight, and colostrum As, especially the most toxic species, inorganic arsenic (iAs), would pose a risk to neonates. PMID- 27549239 TI - HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription. AB - BACKGROUND: Correct disassembly of the HIV-1 capsid shell, called uncoating, is increasingly recognised as central for multiple steps during retroviral replication. However, the timing, localisation and mechanism of uncoating are poorly understood and progress in this area is hampered by difficulties in measuring the process. Previous work suggested that uncoating occurs soon after entry of the viral core into the cell, but recent studies report later uncoating, at or in the nucleus. Furthermore, inhibiting reverse transcription delays uncoating, linking these processes. RESULTS: Here, we have used a combined approach of experimental interrogation of viral mutants and mathematical modelling to investigate the timing of uncoating with respect to reverse transcription. By developing a minimal, testable, model and employing multiple uncoating assays to overcome the disadvantages of each single assay, we find that uncoating is not concomitant with the initiation of reverse transcription. Instead, uncoating appears to be triggered once reverse transcription reaches a certain stage, namely shortly after first strand transfer. CONCLUSIONS: Using multiple approaches, we have identified a point during reverse transcription that induces uncoating of the HIV-1 CA shell. We propose that uncoating initiates after the first strand transfer of reverse transcription. PMID- 27549241 TI - Use of a Dose-Response Model to Study Temporal Trends in Spatial Exposure to Coxiella burnetii: Analysis of a Multiyear Outbreak of Q Fever. AB - The Netherlands underwent a large Q fever outbreak between 2007 and 2009. In this paper, we study spatial and temporal Coxiella burnetii exposure trends during this large outbreak as well as validate outcomes against other published studies and provide evidence to support hypotheses on the causes of the outbreak. To achieve this, we develop a framework using a dose-response model to translate acute Q fever case incidence into exposure estimates. More specifically, we incorporate a geostatistical model that accounts for spatial and temporal correlation of exposure estimates from a human Q fever dose-response model to quantify exposure trends during the outbreak. The 2051 cases, with the corresponding age, gender and residential addresses, reside in the region with the highest attack rates during the outbreak in the Netherlands between 2006 and 2009. We conclude that the multiyear outbreak in the Netherlands is caused by sustained release of infectious bacteria from the same sources, which suggests that earlier implementation of interventions may have prevented many of the cases. The model predicts the risk of infection and acute symptomatic Q fever from multiple exposure sources during a multiple-year outbreak providing a robust, evidence-based methodology to support decision-making and intervention design. PMID- 27549240 TI - Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy. AB - BACKGROUND: Interleukin 12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects in animal tumor models. A combined approach using Paclitaxel and platinum-based doublet chemotherapy is the most commonly used backbone regimen for treating lung cancer. Despite numerous studies regarding the anti-tumor effects of IL-12 and the widespread use of conventional chemotherapy, few direct comparisons of IL-12 and conventional chemotherapy in the treatment of lung cancer have been performed. METHODS: We compared IL-12 to paclitaxel and cisplatin doublet chemotherapy in terms of efficacy against lung cancer in mouse models. The antitumor effect was measured by survival assays, histological analyses and imaging analyses. The cytokine levels were assessed using enzyme linked immunosorbent assay (ELISA) and flow cytometry (FACS). The spleen sizes were measured. CD31, CD105 and Vascular endothelial growth factor receptor 3 (VEGFR3) were analyzed using immunofluorescence. Matrix metalloprotein 9 (MMP-9) and cadherin 1 (CDH1) transcript levels were measured by quantitative PCR. Tumor cells apoptosis were examined by Tunel assay. RESULTS: The results showed that IL-12 treatment inhibited lung tumor growth, resulting in the long term survival of lung cancer-bearing mice. Further examination revealed that IL 12 rapidly activated NK cells to secrete IFN-gamma, resulting in the inhibition of tumor angiogenesis. In contrast, paclitaxel and cisplatin doublet chemotherapy did not show the expected efficacy in orthotopic lung cancer models; the IFN gamma levels were not increased after this treatment, and the number of peripheral lymphocytes was reduced. CONCLUSION: Together, these animal model data indicate that IL-12 shows a better curative effect than PTX + CDDP doublet chemotherapy. PMID- 27549242 TI - Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial. AB - BACKGROUND: REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline alpha-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed. METHODS: An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93). RESULTS: The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391-0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285-0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232-0.926); P = 0.0263]. CONCLUSIONS: In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347. PMID- 27549243 TI - Clinical importance of cine-MRI assessment of small bowel motility in patients with chronic intestinal pseudo-obstruction: a retrospective study of 33 patients. AB - BACKGROUND: Although chronic intestinal pseudo-obstruction (CIPO) is a rare and extremely severe functional digestive disorder, its clinical course and severity show various patterns. We assessed small bowel peristalsis in CIPO patients using cine-MRI (video-motion MRI) and their clinical characteristics to evaluate the clinical importance of performing cine-MRI in patients with this intractable disease. METHODS: The medical records of 131 patients referred to our institution with a suspected diagnosis of CIPO between 2010 and 2015 were retrospectively evaluated. Thirty-three patients (22 female/11 male; age range 16-79 years) who met the criteria for CIPO and underwent cine-MRI were enrolled. Mean luminal diameter (MLD), contraction ratio (CR), and contraction cycle (CC) were determined and compared with these parameters in healthy volunteers. Clinical outcomes in patients with CIPO were also evaluated. RESULTS: The median follow-up time was 25.2 months (range, 1-65 months). Of the 33 patients with CIPO, 23 (70 %) showed apparently disturbed small intestinal peristalsis, whereas 10 (30 %) did not. The percentage of patients requiring intravenous alimentation was significantly higher (p = 0.03), and the mean serum albumin level was significantly lower (p = 0.04), in patients with than without impaired small intestinal peristalsis. Although both cine-MRI and CT findings in the latter ten cases were within the normal range, MLD and CR differed significantly from healthy volunteers. CONCLUSIONS: Cine-MRI is useful in predicting severe clinical features in patients with CIPO, and in detecting slightly impaired small contractility that cannot be detected on CT. PMID- 27549245 TI - Leprosy treatment during pregnancy and breastfeeding: A case report and brief review of literature. AB - Leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to Mycobacterium leprae. It is now infrequent in Europe and is rarely reported during pregnancy. Leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. Therefore, it is important to treat leprosy during pregnancy. This article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug therapy during pregnancy and breastfeeding. The patient delivered a healthy baby girl without perinatal complications, and the infant's growth and development were normal during the 1-year follow-up period. Multidrug therapy consisting of dapsone, rifampicine, and clofazimine is highly effective for people with leprosy and considered safe, both for the mother and the child. Antileprosy drugs are excreted into human milk but there is no report of adverse effects except for skin discoloration of the infant due to clofazimine. Multidrug therapy for leprosy patients should be continued unchanged during pregnancy and breastfeeding. PMID- 27549247 TI - A Dicobalt Complex with an Unsymmetrical Quinonoid Bridge Isolated in Three Units of Charge: A Combined Structural, (Spectro)electrochemical, Magnetic and Spectroscopic Study. AB - Quinonoid ligands are excellent bridges for generating redox-rich dinuclear assemblies. A large majority of these bridges are symmetrically substituted, with examples of unsymmetrically substituted quinonoid bridges being extremely rare. We present here a dicobalt complex in its various redox states with an unsymmetrically substituted quinonoid bridging ligand. Two homovalent forms and one mixed-valent form have been isolated and characterized by single crystal X ray diffraction. The complex displays a large comproportionation constant for the mixed-valent state which is three orders of magnitude higher than that observed for the analogous complex with a symmetrically substituted bridge. Results from electrochemistry, UV/Vis/NIR spectroelectrochemistry, SQUID magnetometry, multi frequency EPR spectroscopy and FIR spectroscopy are used to probe the electronic structures of these complexes. FIR provides direct evidence of exchange coupling. The results presented here display the advantages of using an unsymmetrically substituted bridge: site specific redox chemistry, high thermodynamic stabilization of the mixed-valent form, isolation and crystallization of various redox forms of the complex. This work represents an important step on the way to generating heterodinuclear complexes for use in cooperative catalysis. PMID- 27549301 TI - Editorial Comment to Local recurrence of renal cell carcinoma that simulated multiple renal arteriovenous fistulas after laparoscopic partial nephrectomy: Report of a rare case. PMID- 27549244 TI - Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference. AB - BACKGROUND: Blood tests of liver injury are less well validated in non-alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS: We pre-included new NAFLD patients with biopsy and blood tests from a single-centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary-ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864-0.892) for FibroTest and fibrosis stages, 0.846 (0.830-0.862) for ActiTest and activity grades, and 0.822 (0.804-0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820-0.852; P = 0.0001), FIB4 (0.845; 0.829-0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850-0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non-invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis. PMID- 27549246 TI - Urine metabolomic profiling of children with respiratory tract infections in the emergency department: a pilot study. AB - BACKGROUND: Clinicians lack objective tests to help determine the severity of bronchiolitis or to distinguish a viral from bacterial causes of respiratory distress. We hypothesized that children with respiratory syncytial virus (RSV) infection would have a different metabolomic profile compared to those with bacterial infection or healthy controls, and this might also vary with bronchiolitis severity. METHODS: Clinical information and urine-based metabolomic data were collected from healthy age-matched children (n = 37) and those admitted to hospital with a proven infection (RSV n = 55; Non-RSV viral n = 16; bacterial n = 24). Nuclear magnetic resonance (NMR) measured 86 metabolites per urine sample. Partial least squares discriminant analysis (PLS-DA) was performed to create models of separation. RESULTS: Using a combination of metabolites, a strong PLS-DA model (R2 = 0.86, Q2 = 0.76) was created differentiating healthy children from those with RSV infection. This model had over 90 % accuracy in classifying blinded infants with similar illness severity. Two other models differentiated length of hospitalization and viral versus bacterial infection. CONCLUSION: While the sample sizes remain small, this is the first report suggesting that metabolomic analysis of urine samples has the potential to become a diagnostic aid. Future studies with larger sample sizes are required to validate the utility of metabolomics in pediatric patients with respiratory distress. PMID- 27549303 TI - LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5. AB - Lacticin Q is an unmodified leaderless bacteriocin produced by Lactococcus lactis QU 5. It has been revealed that the production and self-immunity of lacticin Q are facilitated by a gene cluster lnqQBCDEF The gene for a putative TetR-family transcriptional regulator, termed lnqR, was found nearby the lnqQBCDEF cluster, but its involvement in lacticin Q biosynthesis remained unknown. In this study, we created an LnqR-overexpressing QU 5 recombinant by using lactococcal constitutive promoter P32 The recombinant QU 5 showed enhanced production of and self-immunity to lacticin Q. RT-PCR analysis has revealed that an overexpression of LnqR increases the amounts of lnqQBCDEF transcripts, and these six genes are transcribed as an operon in a single transcriptional unit. Interestingly, LnqR expression and thus lacticin Q production by L. lactis QU 5 was found temperature dependent, while LnzR, an LnqR-homologue, in L. lactis QU 14 was expressed in a similar but not identical manner to LnqR, resulting in dissimilar bacteriocin productivities by these strains. This report demonstrates LnqR as the first TetR family transcriptional regulator involved in LAB bacteriocin biosynthesis and that, as an exceptional case of TetR-family regulators, LnqR positively regulates the transcription of these biosynthetic genes. PMID- 27549304 TI - Zika virus: from pathogenesis to disease control. AB - Zika virus is a mosquito-borne flavivirus discovered in Uganda in 1947. The virus has emerged in recent years and spread in the Pacific Area and the Americas, where it has caused large human outbreaks. The factors involved in the virus's emergence are still unknown, but probably include its introduction in naive environments characterised by the presence of high densities of competent Aedes spp. mosquitoes and susceptible human hosts in urban areas. Unique features of Zika virus infection are sexual and transplacental transmission and associated neurological morbidities, i.e. Guillain-Barre syndrome and fetal microcephaly. Diagnosis relies on the detection of viral nucleic acids in biological samples, while detection of a specific antibody response may be inconclusive because of the broad cross-reactivity of antibodies among flaviviruses. Experimental studies have clarified some mechanisms of Zika virus pathogenesis and have identified potential targets for antiviral drugs. In animal models, the virus can infect and efficiently replicate in the placenta and in the brain, and induce fetal demise or neural damage, recapitulating human diseases. These animal models have been used to evaluate candidate vaccines and promising results have been obtained. PMID- 27549302 TI - Upregulation of RGS2: a new mechanism for pirfenidone amelioration of pulmonary fibrosis. AB - BACKGROUND: Pirfenidone was recently approved for treatment of idiopathic pulmonary fibrosis. However, the therapeutic dose of pirfenidone is very high, causing side effects that limit its doses and therapeutic effectiveness. Understanding the molecular mechanisms of action of pirfenidone could improve its safety and efficacy. Because activated fibroblasts are critical effector cells associated with the progression of fibrosis, this study investigated the genes that change expression rapidly in response to pirfenidone treatment of pulmonary fibroblasts and explored their contributions to the anti-fibrotic effects of pirfenidone. METHODS: We used the GeneChip microarray to screen for genes that were rapidly up-regulated upon exposure of human lung fibroblast cells to pirfenidone, with confirmation for specific genes by real-time PCR and western blots. Biochemical and functional analyses were used to establish their anti fibrotic effects in cellular and animal models of pulmonary fibrosis. RESULTS: We identified Regulator of G-protein Signaling 2 (RGS2) as an early pirfenidone induced gene. Treatment with pirfenidone significantly increased RGS2 mRNA and protein expression in both a human fetal lung fibroblast cell line and primary pulmonary fibroblasts isolated from patients without or with idiopathic pulmonary fibrosis. Pirfenidone treatment or direct overexpression of recombinant RGS2 in human lung fibroblasts inhibited the profibrotic effects of thrombin, whereas loss of RGS2 exacerbated bleomycin-induced pulmonary fibrosis and mortality in mice. Pirfenidone treatment reduced bleomycin-induced pulmonary fibrosis in wild type but not RGS2 knockout mice. CONCLUSIONS: Endogenous RGS2 exhibits anti fibrotic functions. Upregulated RGS2 contributes significantly to the anti fibrotic effects of pirfenidone. PMID- 27549305 TI - Gay Male Only-Children: Evidence for Low Birth Weight and High Maternal Miscarriage Rates. AB - Recent findings suggest that there may be a maternal immune response underpinning the etiology of sexual orientation of gay male only-children. This maternal immune response appears to be distinct from that which is purported to explain the classic fraternal birth order effect found in studies of male sexual orientation. We tested two predictions related to the hypothesized maternal immune response in mothers of gay male only-children: (1) elevated fetal loss among mothers who have had gay male only-children and (2) lower birth weight in gay male only-children. Mothers of at least one gay son (n = 54) and mothers of heterosexual son(s) (n = 72) self-reported their pregnancy histories, including the birth weights of newborns and number of fetal losses (e.g., miscarriages). Mothers of gay male only-children (n = 8) reported significantly greater fetal loss compared with mothers of males with four other sibship compositions (gay with no older brothers, gay with older brothers, heterosexual only-children, heterosexual with siblings) (n = 118). Also, firstborn gay male only-children (n = 4) had a significantly lower birth weight than firstborn children in the four other sibship compositions (n = 59). Duration of pregnancy was not significantly different among the groups of firstborn children in the birth weight analyses. Thus, this study found further support for a distinct pattern of maternal immune response implicated in the etiology of male sexual orientation. Mechanisms that may underlie this potential second type of maternal immune response are discussed. PMID- 27549306 TI - The Puzzle of Male Chronophilias. AB - In this article, I return to the idea that pedophilia, a sexual interest in prepubescent children, can be considered a sexual orientation for age, in conjunction with the much more widely acknowledged and discussed sexual orientation for gender. Here, I broaden the scope to consider other chronophilias, referring to paraphilias for age/maturity categories other than young sexually mature adults. The puzzle of chronophilias includes questions about etiology and course, how chronophilias are related to each other, and what they can tell us about how human (male) sexuality is organized. In this article, I briefly review research on nepiophilia (infant/toddlers), pedophilia (prepubescent children), hebephilia (pubescent children), ephebophilia (postpubescent, sexually maturing adolescents), teleiophilia (young sexually mature adults, typically 20s and 30s), mesophilia (middle-aged adults, typically 40s and 50s), and gerontophilia (elderly adults, typically 60s and older) in the context of a multidimensional sexual orientations framework. Relevant research, limitations, and testable hypotheses for future work are identified. PMID- 27549308 TI - Validation of the CLL-IPI and comparison with the MDACC prognostic index in newly diagnosed patients. PMID- 27549307 TI - Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. AB - Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice. PMID- 27549309 TI - The relationship between maternal self-efficacy, compliance and outcome in a trial of vitamin D supplementation in pregnancy. AB - : In a randomised controlled trial of vitamin D during pregnancy, we demonstrated that women with lower self-efficacy were more likely to experience practical problems with taking the trial medication and that this was associated with lower compliance and achieved 25(OH)-vitamin D concentrations. INTRODUCTION: The relationship between self-efficacy (the belief that one can carry out a behaviour), compliance with study protocol and outcome was explored within a randomised, double-blind, placebo-controlled trial of vitamin D supplementation in pregnancy. METHODS: In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial, women with circulating plasma 25(OH)-vitamin D of 25-100 nmol/l in early pregnancy were randomised to either 1000 IU cholecalciferol/day or matched placebo from 14 weeks until delivery. Circulating 25(OH)-vitamin D concentrations were assessed at 14 and 34 weeks' gestation. A sequential sub-sample completed Schwarzer's General Self-Efficacy Scale at 14 and 34 weeks and the Problematic Experiences of Therapy Scale at 34 weeks. Women were interviewed about their experiences of the trial and interview transcripts analysed thematically. RESULTS: In 203 women, those with higher self-efficacy were less likely to experience practical problems taking the study medication (odds ratio (OR) 0.81 (95 % confidence interval (CI) 0.69-0.95), p = 0.01). Over half reported practical problems associated with poorer compliance with the protocol requiring women to take the medication daily. Compliance in women who experienced practical problems was 94 % compared with 98 % for those with no problems (p < 0.001). Poorer compliance was also associated with lower concentrations of 25(OH)-D in late pregnancy in the treatment group (beta = 0.54 nmol/l (95 % CI 0.18-0.89), p = 0.003). Thematic analysis suggested common difficulties were remembering to take the medication every day and swallowing the large capsules. CONCLUSIONS: These findings suggest that differences in self-efficacy influence trial outcomes. Such information may help clinicians anticipate responses to routine vitamin D supplementation in pregnancy and identify those who may need more support to comply. TRIAL REGISTRATION: ISRCTN82927713, registered 11/04/2008. PMID- 27549310 TI - Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and Mechanisms of Resistance. AB - Lincosamides, streptogramins, phenicols, and pleuromutilins (LSPPs) represent four structurally different classes of antimicrobial agents that inhibit bacterial protein synthesis by binding to particular sites on the 50S ribosomal subunit of the ribosomes. Members of all four classes are used for different purposes in human and veterinary medicine in various countries worldwide. Bacteria have developed ways and means to escape the inhibitory effects of LSPP antimicrobial agents by enzymatic inactivation, active export, or modification of the target sites of the agents. This review provides a comprehensive overview of the mode of action of LSPP antimicrobial agents as well as of the mutations and resistance genes known to confer resistance to these agents in various bacteria of human and animal origin. PMID- 27549312 TI - A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein. AB - BACKGROUND: CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions. RESULTS: We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size. CONCLUSIONS: This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses. PMID- 27549311 TI - p53 and the Carcinogenicity of Chronic Inflammation. AB - Chronic inflammation is a major cancer predisposition factor. Constitutive activation of the inflammation-driving NF-kappaB pathway commonly observed in cancer or developed in normal tissues because of persistent infections or endogenous tissue irritating factors, including products of secretion by senescent cells accumulating with age, markedly represses p53 functions. In its turn, p53 acts as a suppressor of inflammation helping to keep it within safe limits. The antagonistic relationship between p53 and NF-kappaB is controlled by multiple mechanisms and reflects cardinal differences in organismal responses to intrinsic and extrinsic cell stresses driven by these two transcription factors, respectively. This provides an opportunity for developing drugs to treat diseases associated with inappropriate activity of either p53 or NF-kappaB through targeting the opposing pathway. Several drug candidates of this kind are currently in clinical testing. These include anticancer small molecules capable of simultaneous suppression of p53 and activation of NF-kappaB and NF-kappaB activating biologics that counteract p53-mediated pathologies associated with systemic genotoxic stresses such as acute radiation syndrome and side effects of cancer treatment. PMID- 27549313 TI - Protective effect of sevoflurane preconditioning on ischemia-reperfusion injury in patients undergoing reconstructive plastic surgery with microsurgical flap, a randomized controlled trial. AB - BACKGROUND: In many clinical conditions that involve free flaps and tissue transplantations the possibility of minimizing ischemia-reperfusion injury can be a determinant factor for the success of the surgery itself. We hypothesize that preconditioning with sevoflurane is a protective factor against ischemia reperfusion injury. METHODS: In this randomized controlled trial, patients ASA I II undergoing breast reconstruction with deep inferior epigastric perforator flaps were allocated into two groups and analyzed: group BAL included patients who received balanced anesthesia with sevoflurane for 30 min before removal of the flap and throughout the surgery. The TCI group included patients who received a total intravenous anesthesia with propofol and remifentanil. We evaluated regional tissue oximetry at the end of the surgery and at 4, 12 and 20 h after surgery. Other assessed parameters were: blood lactate clearance, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, creatine phosphokinase. RESULTS: In total 54 patients, twenty-seven per group, were analyzed. There was a significant increase of the average value of regional tissue oximetry measured 4 h after surgery in the BAL group compared to the TCI group: BAL: 84.05 % (8.96 SD); TCI : 76.17 % (12.92 SD) (P = 0.03), but not at the other time frames. The creatine phosphokinase value was significantly lower in the BAL group at the end of surgery, but not at the other time-frames. There were no significant differences in blood levels of other markers. CONCLUSIONS: From our results, the positive preconditioning impact of sevoflurane on ischemia reperfusion injury in patients undergoing free flap surgery is expressed in the early postoperative hours, but it does not persist in the long-term. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01905501 . Registered July 18, 2013. PMID- 27549314 TI - Immunological evaluation of personalized peptide vaccination for patients with histologically unfavorable carcinoma of unknown primary site. AB - The immunological characteristics of carcinoma of unknown primary site (CUP) are not well established due to inclusion of heterogeneous types of metastatic tumors with the absence of any detectable primary site. We evaluated the immune responses in patients with histologically unfavorable CUP during personalized peptide vaccination (PPV). Ten patients with histologically unfavorable CUP who had been treated by PPV after chemotherapy failure were analyzed. In PPV treatment, up to four human leukocyte antigen-matched peptides of a total 31 peptides were selected according to preexisting host immunity before vaccination and administered subcutaneously. Peptides derived from the Lck antigen were most often chosen for use among all patients. CTL responses were increased in 8 of the 10 and 5 of the five patients tested at the end of the first and second PPV cycles, respectively. Increases in humoral responses after vaccination, including IgG, IgG1, IgG3, IgA, and IgM, were observed against not only the vaccinated peptides but also the non-vaccinated peptides. Severe adverse events due to PPV were not observed. Median overall survival was 13.9 months (95 % CI 4.0-22.5 months). PPV activated both cellular and humoral immune responses to short peptides derived from CTL epitopes in the majority of CUP patients. PPV with Lck derived peptides may be a feasible, new treatment modality for histologically unfavorable CUP patients due to its safety and strong ability to boost immune responses, although its clinical efficacy remains to be investigated in larger scale trials. PMID- 27549315 TI - Glycosphingolipid dynamics in human embryonic stem cell and cancer: their characterization and biomedical implications. AB - Glycosphingolipids (GSLs) are composed of complex glycans linked to sphingosines and various fatty acid chains. Antibodies against several GSLs designated as stage-specific embryonic antigens (SSEAs), have been widely used to characterize differentiation of embryonic stem (ES) cells. In view of the cross-reactivities of these antibodies with multiple glycans, a few laboratories have employed advanced mass spectrometry (MS) technologies to define the dynamic changes of surface GSLs upon ES differentiation. However, the amphiphilic nature and heterogeneity of GSLs make them difficult to decipher. In our studies, systematic survey of GSL expression profiles in human ES cells and differentiated derivatives was conducted, primarily with matrix-assisted laser desorption/ionization MS (MALDI-MS) and MS/MS analyses. In addition to the well known ES-specific markers, SSEA-3 and SSEA-4, several previously undisclosed globo- and lacto-series GSLs, including Gb4Cer, Lc4Cer, fucosyl Lc4Cer, Globo H, and disialyl Gb5Cer were identified in the undifferentiated human ES and induced pluripotent stem cells. Furthermore, during differentiation to embryoid body outgrowth, the core structures of GSLs switched from globo- and lacto- to ganglio series. Lineage-specific differentiation was also marked by alterations of specific GSLs. During differentiation into neural progenitors, core structures shifted to primarily ganglio-series dominated by GD3. GSL patterns shifted to prominent expression of Gb4Cer with little SSEA-3 and- 4 or GD3 during endodermal differentiation. Several issues relevant to MS analysis and novel GSLs in ES cells were discussed. Finally, unique GSL signatures in ES and cancer cells are exploited in glycan-targeted anti-cancer immunotherapy and their mechanistic investigations were discussed using anti-GD2 mAb and Globo H as examples. PMID- 27549317 TI - Erratum to: Characterization of Pharmacokinetics in the Gottingen Minipig with Reference Human Drugs: An In Vitro and In Vivo Approach. PMID- 27549316 TI - Orthostatic hypotension: prevalence and associated risk factors among the ambulatory elderly in an Asian population. AB - INTRODUCTION: The prevalence of orthostatic hypotension (OH) among the elderly population in Singapore, as defined by a decline in blood pressure upon a change in position, is not well-established. Studies associate OH with clinically significant outcomes such as falls. This study aims to determine the prevalence of OH among elderly patients attending a public primary care clinic (polyclinic) for chronic disease management, and examine the relationships between postulated risk factors and OH. METHODS: Patients aged >= 65 years attending a typical polyclinic in Geylang were identified and targeted for recruitment at the study site. A questionnaire on symptoms and postulated risk factors was administered, followed by supine and standing blood pressure measurements. Cross-sectional analysis was performed with independent sample t-test for continuous data and chi square test for categorical data. Prevalence rate ratios with 95% confidence interval were calculated for the latter. RESULTS: A total of 364 multiethnic patients participated in the study. The prevalence of OH was 11.0%. Older age, comorbidities such as cardiac failure and kidney disease, being physically inactive at work, fatigue, self-reported dizziness in the past year, and the use of loop diuretics were found to be significantly associated with OH. CONCLUSION: About one in ten elderly patients at a local polyclinic was affected by OH, which was associated with multiple factors. Some of these factors are modifiable and can be addressed to reduce the incidence of OH. PMID- 27549319 TI - Digitally deconvolving the tumor microenvironment. AB - Understanding a tumor's complex cellular heterogeneity will be crucial for the development of better treatment strategies. A new study suggests a novel method for the in silico dissociation of solid tumors and presents novel insights that have implications for immunotherapy in cancer.Please see the related Research article: www.dx.doi.org/10.1186/s13059-016-1028-7 . PMID- 27549318 TI - Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs. AB - Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stressors, predisposing to major adverse clinical outcomes, including hospitalization, institutionalization, disability, and death in the general population of older adults. As the proportion of older adults living with HIV increases in the era of antiretroviral therapy, frailty is increasingly recognized to be of significant clinical and public health relevance to the HIV-infected population. This article reviews current knowledge on the epidemiology and biology of frailty and its potential role as a target for reducing disparities in outcomes in HIV; conceptual frameworks and current approaches to frailty measurement; existing data on frailty interventions; and important areas for future research focus necessary to develop and advance effective strategies to prevent or ameliorate frailty and its marked adverse consequences among people living with HIV. PMID- 27549324 TI - Selected Abstracts from XXXIII National Congress of the Italian Society of Hypertension (SIIA), Florence, 6-8 October 2016. PMID- 27549323 TI - Mapping of fiber quality QTLs reveals useful variation and footprints of cotton domestication using introgression lines. AB - Fiber quality improvement is a driving force for further cotton domestication and breeding. Here, QTLs for fiber quality were mapped in 115 introgression lines (ILs) first developed from two intraspecific populations of cultivated and feral cotton landraces. A total of 60 QTLs were found, which explained 2.03-16.85% of the phenotypic variance found in fiber quality traits. A total of 36 markers were associated with five fiber traits, 33 of which were found to be associated with QTLs in multiple environments. In addition, nine pairs of common QTLs were identified; namely, one pair of QTLs for fiber elongation, three pairs for fiber length, three pairs for fiber strength and two pairs for micronaire (qMICs). All common QTLs had additive effects in the same direction in both IL populations. We also found five QTL clusters, allowing cotton breeders to focus their efforts on regions of QTLs with the highest percentages of phenotypic variance. Our results also reveal footprints of domestication; for example, fourteen QTLs with positive effects were found to have remained in modern cultivars during domestication, and two negative qMICs that had never been reported before were found, suggesting that the qMICs regions may be eliminated during artificial selection. PMID- 27549325 TI - High-Definition Video Telescope-Assisted Ventral Slot Decompression Surgery for Cervical Intervertebral Disc Herniation in 30 Dogs. AB - OBJECTIVE: To describe the use of a video telescope operating monitor (VITOMTM) for ventral slot decompression and to report its clinical applications using preoperative and postoperative computed tomography (CT) myelography. STUDY DESIGN: Prospective case series. ANIMALS: Consecutive dogs presented with cervical intervertebral disc disease requiring surgical decompression (n = 30). METHODS: Demographic data, preoperative neurological status, localization and lateralization of the compression, total operative time, surgical complications, ventral slot size and orientation, hospitalization time, and postoperative outcome were recorded. Preoperative and postoperative spinal cord area at the compression site and ratios of compressed to normal spinal cord area were calculated by CT myelography. RESULTS: French Bulldogs were the most common breed of dogs (n = 15; 50%) and neck pain was the most common neurological sign (n = 18; 60%). Postoperative CT myelography confirmed that spinal cord decompression, postoperative spinal cord area, and the ratios of compressed to normal spinal cord area improved significantly compared with preoperative measurements (P = .01). Sinus bleeding occurred in 20% of dogs. The mean ratios (+/- SD) of ventral slot length and width compared with vertebral body length and width were 0.21 +/- 0.08 and 0.31 +/- 0.07, respectively. The mean postoperative hospitalization time was 3.0 +/- 0.6 days and all dogs showed clinical improvement and an excellent outcome. CONCLUSION: The VITOMTM ventral slot decompression technique was fast and easy to perform. It allowed a minimally invasive approach with a small ventral slot while improving spinal cord visualization. The results of this study support the use of the VITOMTM technique in spinal veterinary surgery. PMID- 27549326 TI - Positive selection on panpulmonate mitogenomes provide new clues on adaptations to terrestrial life. AB - BACKGROUND: Transitions from marine to intertidal and terrestrial habitats resulted in a significant adaptive radiation within the Panpulmonata (Gastropoda: Heterobranchia). This clade comprises several groups that invaded the land realm independently and in different time periods, e.g., Ellobioidea, Systellomatophora, and Stylommatophora. Thus, mitochondrial genomes of panpulmonate gastropods are promising to screen for adaptive molecular signatures related to land invasions. RESULTS: We obtained three complete mitochondrial genomes of terrestrial panpulmonates, i.e., the ellobiid Carychium tridentatum, and the stylommatophorans Arion rufus and Helicella itala. Our dataset consisted of 50 mitogenomes comprising almost all major panpulmonate lineages. The phylogenetic tree based on mitochondrial genes supports the monophyly of the clade Panpulmonata. Terrestrial lineages were sampled from Ellobioidea (1 sp.) and Stylommatophora (9 spp.). The branch-site test of positive selection detected significant non-synonymous changes in the terrestrial branches leading to Carychium (Ellobiodea) and Stylommatophora. These convergent changes occurred in the cob and nad5 genes (OXPHOS complex III and I, respectively). CONCLUSIONS: The convergence of the non-synonymous changes in cob and nad5 suggest possible ancient episodes of positive selection related to adaptations to non-marine habitats. The positively selected sites in our data are in agreement with previous results in vertebrates suggesting a general pattern of adaptation to the new metabolic requirements. The demand for energy due to the colonization of land (for example, to move and sustain the body mass in the new habitat) and the necessity to tolerate new conditions of abiotic stress may have changed the physiological constraints in the early terrestrial panpulmonates and triggered adaptations at the mitochondrial level. PMID- 27549327 TI - Misoprostol Vaginal Insert in Labor Induction: A Cost-Consequences Model for 5 European Countries-An Economic Evaluation Supported with Literature Review and Retrospective Data Collection. AB - INTRODUCTION: The present study aimed to assess the costs and consequences of using an innovative medical technology, misoprostol vaginal insert (MVI), for the induction of labor (IOL), in place of alternative technologies used as a standard of care. METHODS: This was a retrospective study on cost and resource utilization connected with economic model development. Target population were women with an unfavorable cervix, from 36 weeks of gestation, for whom IOL is clinically indicated. Data on costs and resources was gathered via a dedicated questionnaire, delivered to clinical experts in five EU countries. The five countries participating in the project and providing completed questionnaires were Austria, Poland, Romania, Russia and Slovakia. A targeted literature review in Medline and Cochrane was conducted to identify randomized clinical trials meeting inclusion criteria and to obtain relative effectiveness data on MVI and the alternative technologies. A hospital perspective was considered as most relevant for the study. The economic model was developed to connect data on clinical effectiveness and safety from randomized clinical trials with real life data from local clinical practice. RESULTS: The use of MVI in most scenarios was related to a reduced consumption of hospital staff time and reduced length of patients' stay in hospital wards, leading to lower total costs with MVI when compared to local comparators. CONCLUSIONS: IOL with the use of MVI generated savings from a hospital perspective in most countries and scenarios, in comparison to alternative technologies. FUNDING: Sponsorship, article processing charges, and the open access charge for this study were funded by Ferring Pharmaceuticals Poland. PMID- 27549328 TI - Attitudes towards human papillomavirus vaccination among African parents in a city in the north of England: a qualitative study. AB - BACKGROUND: Human papillomavirus (HPV) is sexually transmitted and has been conclusively linked to cervical cancer and genital warts. Cervical cancer is attributed to approximately 1100 deaths annually in UK, and is the second most common female cancer globally. It has been suggested that black African women are more predisposed to HPV infection and cervical cancer. A vaccine has been developed to reduce HPV infection, and in the UK, has been offered to 12-13 year old adolescent girls through schools as part of their childhood immunization programme since 2008. Upon programme initiation, it was noted that vaccine uptake was lower in schools where girls from ethnic minority groups were proportionately higher. The study's objectives were to explore factors influencing UK based African parents' acceptance or decline of the HPV vaccine, whether fathers and mothers share similar views pertaining to vaccination and any interfamily tensions resulting from differing views. METHODS: A qualitative study was conducted with five African couples residing in north England. Face to face semi structured interviews were carried out. Participants were parents to at least one daughter aged between 8 and 14 years. Recruitment was done through purposive sampling using snowballing. RESULTS: HPV and cervical cancer awareness was generally low, with awareness lower in fathers. HPV vaccination was generally unacceptable among the participants, with fear of promiscuity, infertility and concerns that it's still a new vaccine with yet unknown side effects cited as reasons for vaccine decline. There was HPV risk denial as religion and good cultural upbringing seemed to result in low risk perceptions, with HPV and cervical cancer generally perceived as a white person's disease. Religious values and cultural norms influenced vaccine decision-making, with fathers acting as the ultimate decision makers. Current information about why the vaccine is necessary was generally misunderstood. CONCLUSION: Tailored information addressing religious and cultural concerns may improve vaccine acceptability in African parents. PMID- 27549329 TI - Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection. AB - BACKGROUND: Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. METHODS: A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. RESULTS: The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B.) abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine disease underreporting. We found no studies of disease incidence estimates or disease control efforts. CONCLUSION: The risk for re-emergence and transmission of brucellosis is evident as a result of the co-existence of animal husbandry activities and social-cultural activities that promote brucellosis transmission. Well-designed countrywide, evidence-based, and multidisciplinary studies of brucellosis at the human/livestock/wildlife interface are needed. These could help to generate reliable frequency and potential impact estimates, to identify Brucella reservoirs, and to propose control strategies of proven efficacy. PMID- 27549330 TI - Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes. METHODS: The expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2-3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies. RESULTS: Positive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells' motility and growth ability. Knock down of EIF5A2 in NPC cells decreased the cell's motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu. CONCLUSIONS: Our findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress. PMID- 27549331 TI - Definitive chemoradiotherapy for squamous head and neck cancer: cisplatin versus carboplatin? A meta-analysis. AB - AIM: Concomitant chemoradiotherapy (with cisplatin or carboplatin) is an option of definitive treatment for squamous head and neck cancer. We aimed to perform a meta-analysis comparing those two platinum agents. MATERIALS & METHODS: We carried out a systematic search on English literature between 1990 and 17 April 2015 according to the Cochrane review guidelines. RESULTS: Five of 60 studies fulfilled inclusion criteria with 491 patients. There was no difference in response rate. Cisplatin tends to be more active systemically than carboplatin, without statistically significance; 5-year survival rate: 30 and 27%, respectively (p = 0.33). CONCLUSION: Despite the trend to improved outcomes in using cisplatin, carboplatin is also active and can be a reasonable option to treat patients. PMID- 27549332 TI - Laser may reduce recurrence rate in pilonidal sinus disease by reducing captured occipital hair. PMID- 27549333 TI - Solvent type influences bond strength to air or blot-dried dentin. AB - BACKGROUND: Air-drying of etched and rinsed dentin surface may force the exposed collagen fibrils to collapse. Blot-drying is an alternative method to wipe the excess water from the dentin surface without compromising the monomer penetration. Contemporary total etch adhesives contain ethanol/water or acetone as solvent in which resin monomers are dissolved. Solvent type of the adhesive system has an important role in bonding to dentin. An adhesive containing tertiary butanol as an alternative solvent has been in the market. Purpose of this study is to determine the shear bond strengths of three total-etch adhesives with different solvents (acetone, ethanol or tertiary butanol) applied to air or blot dried moist dentin. METHODS: Sixty extracted non-carious human third molars were divided into three main groups according to solvent content of the adhesives [acetone based - One Step (OS, Bisco, IL, USA); ethanol/water based - Optibond Solo Plus (OB, Kerr, CA, USA); and tertiary butanol based - XP Bond (XP, Caulk/Dentsply, DE, USA)]. Each main group was divided into two groups according to drying methods (blot or air) (n = 10). Shear bond strengths (SBS) were measured. Data were analyzed by Student's t test and Tukey HSD test (p < 0,05). RESULTS: XP showed highest SBS values in both drying methods applied (p < 0.05). Drying method did not influence the SBS in OS and OB (p > 0.05). XP-blot produced significantly higher SBS than XP-air (p < 0.05). CONCLUSIONS: Tertiary butanol based adhesive showed higher bond strength values than ethanol or acetone based adhesives. Blot drying of dentin improved the bond strength values of tertiary butanol based adhesive. Further research is necessary to determine in vivo and in vitro performance of tertiary butanol based adhesives. PMID- 27549334 TI - Pediatric bone tumors in Germany from 1987 to 2011: incidence rates, time trends and survival. AB - BACKGROUND: Malignant bone tumors are a rare group of childhood cancer. MATERIALS AND METHODS: This study describes incidence rates, survival probabilities, and time trends for 1831 children below 15 years of age with a bone tumor registered at the population-based German Childhood Cancer Registry between 1987 and 2011. RESULTS: Overall age-standardized annual incidence rate (ASR) was 5.5 per million. Osteosarcomas (ASR 2.8) and Ewing tumors (ASR 2.6) were the most frequent diagnostic groups. The incidence of bone tumors overall tended to increase slightly over time by 0.7% each year on average. Thirty-nine of the bone tumor cases reported were subsequent primaries and not included into the survival analysis. Survival probabilities remained largely constant. DISCUSSION: Possibly survival was largely constant because chemotherapy has not changed much over time. Overall, the results are similar to other results reported from Europe. PMID- 27549335 TI - Continuous spinal labor analgesia for two deliveries in a parturient with severe subvalvular aortic stenosis. AB - Various degrees of left ventricular outflow tract (LVOT) obstruction have been seen in patients with subvalvular aortic stenosis (SAS). Regional analgesia during labor for parturients with SAS is relatively contraindicated because it has a potential risk for hemodynamic instability due to sympathetic blockade as a result of vasodilation by local anesthetics. We thought continuous spinal analgesia (CSA) using an opioid and minimal doses of local anesthetic could provide more stable hemodynamic status. We demonstrate the management of a 28 year-old pregnant patient with SAS who received CSA for her two deliveries. For her first delivery (peak pressure gradient (?P) between LV and aorta was approximately 55 mmHg), intrathecal fentanyl was used as a basal infusion, but we needed a small amount of bupivacaine to provide supplemental intrathecal analgesia as labor progressed. Although there were mild fluctuations in hemodynamics, she was asymptomatic. For her second delivery (?P between LV and aorta was approximately 90 mmHg), minimal doses of continuous bupivacaine were used as a basal infusion. For her additional analgesic requests, bolus co administration of fentanyl was effective. There were no fluctuations in her hemodynamics. Although her SAS in her second pregnancy was more severe than in the first, her hemodynamics exhibited less fluctuation during the second delivery with this method. In conclusion, CSA using fentanyl combined with minimal doses of bupivacaine provided satisfactory analgesia and stable hemodynamics in parturient with severe SAS. PMID- 27549336 TI - The effects of intensive care environment on postoperative nightmare. AB - PURPOSE: We retrospectively investigated the incidence of postoperative nightmares and evaluated the impact of postoperative intensive care on the incidence of during subsequent hospital stay. To reduce the effect of selection bias, we compared the incidence of nightmares in propensity-matched pairs with postoperative management in ICUs or in surgical wards. METHODS: This is a retrospective review of an institutional registry containing 21,606 anesthesia cases and was conducted with ethics board approval. Outcomes of surgical patients treated in ICUs and in postsurgical wards (ICU admission vs non ICU admission) were compared first for nightmares using the initial 12,508 patients. To avoid channeling bias, propensity score analysis was used to generate a set of matched cases (ICU admission) and controls (non ICU admission), yielding 642 matched patient pairs. The incidence rate of nightmares was compared as the primary outcome. RESULTS: Before adjusting patients' characteristics, ICU environment exposure increased the incidence of nightmares compared with non-ICU environment during subsequent hospital stay [ICU vs non-ICU: 101/718 (12.3 %) vs 1147/10,542 (9.81 %)]. The odds ratio (95 % CIs) for ICU was 1.29 (1.03-1.61) for nightmares (p = 0.022). After propensity score matching, however, an equal rate of nightmares occurred in the ICU environment exposure compared to the non-ICU environment [ICU vs non-ICU: 81/561 (12.6 %) vs 73/569 (11.4 %)]. The odds ratio and 95 % CIs for ICU were 1.13 (0.80-1.58) for nightmares (p = 0.54). CONCLUSIONS: The incidence of nightmares did not become more evident during subsequent hospital stay after ICU environment exposure. PMID- 27549337 TI - Racial Differences in Hospitalizations of Dying Medicare-Medicaid Dually Eligible Nursing Home Residents. AB - OBJECTIVES: To examine whether racial differences in end-of-life (EOL) hospitalizations vary according to the presence of advance directives, specifically do-not-hospitalize (DNH) orders, and individual cognitive status in nursing home (NH) residents. DESIGN: National data, including Medicare data and Minimum Data Set (MDS) 2.0, between January 1, 2007, and September 30, 2010, were linked. EOL hospitalizations were hospitalizations in the last 30 days of life. Linear probability models with an interaction term (between race and DNH) and NH fixed-effects were estimated. The analyses were stratified according to cognitive status. SETTING: Nursing homes in the United States. PARTICIPANTS: Dually eligible Medicare-Medicaid decedents enrolled in Medicare fee-for-service plans and long-stay NH residents (in NHs >= 90 days before death) (N = 394,948). MEASUREMENTS: Racial difference in EOL hospitalizations from a NH. RESULTS: End of-life hospitalization rate was 31.7% for whites and 42.8% for blacks. For participants without DNH orders, adjusted probability of EOL hospitalization was higher for blacks than for whites: 2.7 percentage points in those with moderate cognitive impairment (P < .001) and 4.7 percentage points in those with severe cognitive impairment (P < .001). For those with DNH orders, adjusted racial differences in EOL hospitalization were not statistically significant in those with moderate (P = .25) or severe (P = .93) cognitive impairment, but blacks had a higher probability of EOL hospitalization than whites if they had relatively intact cognitive status. CONCLUSION: Racial differences in EOL hospitalization varied with DNH orders and cognitive status in dying residents. Future research is necessary to understand the reasons behind these variations. PMID- 27549338 TI - High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons. AB - Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1(ARH)) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1(ARH) neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1(ARH) neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1(ARH) neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1(ARH) neurons. We propose that Kiss1(ARH) neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. PMID- 27549339 TI - Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. AB - The FDA approved drug rapamycin increases lifespan in rodents and delays age related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome. PMID- 27549340 TI - Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. AB - Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density. PMID- 27549341 TI - Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer. AB - Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 postmenopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected 2 h after exemestane dosing at a 1- or 3-month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) single nucleotide polymorphism (SNP) would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates. CYP3A4*22 was associated with a 54% greater exemestane concentration (P<0.01). Concentration was greater in patients who reported White race, had elevated aminotransferases, renal insufficiency, lower body mass index and had not received chemotherapy (all P<0.05), and CYP3A4*22 maintained significance after adjustment for covariates (P<0.01). These genetic and clinical predictors of exemestane concentration may be useful for treatment individualization in patients with breast cancer. PMID- 27549344 TI - Structural, Electronic, and Optical Properties of BiOX1-xYx (X, Y = F, Cl, Br, and I) Solid Solutions from DFT Calculations. AB - Six BiOX1-xYx (X, Y = F, Cl, Br, and I) solid solutions have been systematically investigated by density functional theory calculations. BiOCl1-xBrx, BiOBr1-xIx, and BiOCl1-xIx solid solutions have very small bowing parameters; as such, some of their properties increase almost linearly with increasing x. For BiOF1-xYx solid solutions, the bowing parameters are very large and it is extremely difficult to fit the related calculated data by a single equation. Consequently, BiOX1-xYx (X, Y = Cl, Br, and I) solid solutions are highly miscible, while BiOF1 xYx (Y = Cl, Br, and I) solid solutions are partially miscible. In other words, BiOF1-xYx solid solutions have miscibility gaps or high miscibility temperature, resulting in phase separation and F/Y inhomogeneity. Comparison and analysis of the calculated results and the related physical-chemical properties with different halogen compositions indicates that the parameters of BiOX1-xYx solid solutions are determined by the differences of the physical-chemical properties of the two halogen compositions. In this way, the large deviation of some BiOX1 xYx solid solutions from Vegard's law observed in experiments can be explained. Moreover, the composition ratio of BiOX1-xYx solid solutions can be measured or monitored using optical measurements. PMID- 27549342 TI - HIV-1 Tat protein vaccination in mice infected with Mycobacterium tuberculosis is safe, immunogenic and reduces bacterial lung pathology. AB - BACKGROUND: The therapeutic HIV-1 Tat protein vaccine is in advanced clinical development. Tuberculosis, the main AIDS co-infection, is highly endemic in areas where AIDS prevention through vaccination is needed. However, safety and immunogenicity of Tat vaccination in the course of Mycobacterium tuberculosis (Mtb) infection is still unknown and it prevents the possibility to administer the vaccine to Mtb-infected individuals. We addressed the interplay and effects of Tat vaccination on Mtb infection in immunocompetent mice. METHODS: C57BL/6 mice were vaccinated or not with Bacillus Calmette-Guerin (BCG), the current tuberculosis vaccine, and after 5 weeks were infected with Mtb by intravenous route. The Tat protein was injected intradermally at 1, 2 and 4 weeks after Mtb challenge. Eight weeks after Mtb infection, all mice were sacrificed, and both the degree of pathology and immune responses to Mtb and Tat were evaluated. As additional control, some mice were either vaccinated or not with BCG, were not challenged with Mtb, but received the Tat protein. Statistical significances were evaluated by one-way or two-way ANOVA and Tukey's multiple comparisons post-test. RESULTS: In the lungs of Mtb-infected mice, Tat-vaccine did not favour Mtb replication and indeed reduced both area of cellular infiltration and protein levels of Interferon-gamma, Chemokine (C-C motif) ligand-4 and Interleukin-1beta, pathological events triggered by Mtb-infection. Moreover, the protection against Mtb infection conferred by BCG remained good after Tat protein treatment. In spleen cells of Mtb-infected mice, Tat vaccination enhanced Mtb-specific Interferon-gamma and Interleukin-17 responses, which may have a protective role. Of note, Mtb infection reduced, but did not suppress, the development of anti-Tat antibodies, required for Tat vaccine efficacy and the titer of anti-Tat IgG was potentiated by BCG vaccination in Mtb-free mice. In general, Tat treatment was well tolerated in both Mtb-infected and Mtb-free mice. CONCLUSIONS: Tat protein vaccine, administered in Mtb-infected mice with a protocol resembling that used in the clinical trials, was safe, immunogenic, limited the lung Mtb-associated immunopathology and did not abrogate the protective efficacy of BCG. These data provide preliminary evidence for a safe use of Tat vaccine in people vaccinated with BCG and/or suffering from tuberculosis. PMID- 27549345 TI - Application of a Web-Enabled Leg Training System for the Objective Monitoring and Quantitative Analysis of Exercise-Induced Fatigue. AB - BACKGROUND: Sustained cardiac rehabilitation is the key intervention in the prevention and treatment of many human diseases. However, implementation of exercise programs can be challenging because of early fatigability in patients with chronic diseases, overweight individuals, and aged people. Current methods of fatigability assessment are based on subjective self-reporting such as rating of perceived exertion or require specialized laboratory conditions and sophisticated equipment. A practical approach allowing objective measurement of exercise-induced fatigue would be useful for the optimization of sustained delivery of cardiac rehabilitation to improve patient outcomes. OBJECTIVES: The objective of this study is to develop and validate an innovative approach, allowing for the objective assessment of exercise-induced fatigue using the Web enabled leg rehabilitation system. METHODS: MedExercise training devices were equipped with wireless temperature sensors in order to monitor their usage by temperature rise in the resistance unit (Delta t degrees ). Since Delta t degrees correlated with the intensity and duration of exercise, this parameter was used to characterize participants' leg work output (LWO). Personal smart devices such as laptop computers with wireless gateways and relevant software were used for monitoring of self-control training. Connection of smart devices to the Internet and cloud-based software allowed remote monitoring of LWO in participants training at home. Heart rates (HRs) were measured by fingertip pulse oximeters simultaneously with Delta t degrees in 7 healthy volunteers. RESULTS: Exercise-induced fatigue manifested as the decline of LWO and/or rising HR, which could be observed in real-time. Conversely, training at the steady-state LWO and HR for the entire duration of exercise bout was considered as fatigue-free. The amounts of recommended daily physical activity were expressed as the individual Delta t degrees values reached during 30-minute fatigue-free exercise of moderate intensity resulting in a mean of 8.1 degrees C (SD 1.5 degrees C, N=7). These Delta t degrees values were applied as the thresholds for sending automatic notifications upon taking the personalized LWO doses by self-control training at home. While the mean time of taking LWO doses was 30.3 (SD 4.1) minutes (n=25), analysis of times required to reach the same Delta t degrees by the same participant revealed that longer durations were due to fatigability, manifesting as reduced LWO at the later stages of training bouts. Typically, exercising in the afternoons associated with no fatigue, although longer durations of evening sessions suggested a diurnal fatigability pattern. CONCLUSIONS: This pilot study demonstrated the feasibility of objective monitoring of fatigue development in real-time and online as well as retrospective fatigability quantification by the duration of training bouts to reach the same exercise dose. This simple method of leg training at home accompanied by routine fatigue monitoring might be useful for the optimization of exercise interventions in primary care and special populations. PMID- 27549346 TI - Comparison of Monofractal, Multifractal and gray level Co-occurrence matrix algorithms in analysis of Breast tumor microscopic images for prognosis of distant metastasis risk. AB - Breast cancer prognosis is a subject undergoing intense study due to its high clinical relevance for effective therapeutic management and a great patient interest in disease progression. Prognostic value of fractal and gray level co occurrence matrix texture analysis algorithms has been previously established on tumour histology images, but without any direct performance comparison. Therefore, this study was designed to compare the prognostic power of the monofractal, multifractal and co-occurrence algorithms on the same set of images. The investigation was retrospective, with 51 patients selected on account of non metastatic IBC diagnosis, stage IIIB. Image analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Bootstrap-corrected Cox proportional hazards regression P-values indicated a significant association with metastasis outcome of at least one of the features within each group. AUC values were far better for co-occurrence (0.66-0.77) then for fractal features (0.60-0.64). Correction by the split-sample cross-validation likewise indicated the generalizability only for the co-occurrence features, with their classification accuracies ranging between 67 and 72 %, while accuracies of monofractal and multifractal features were reduced to nearly random 52-55 %. These findings indicate for the first time that the prognostic value of texture analysis of tumour histology is less dependent on the morphological complexity of the image as measured by fractal analysis, but predominantly on the spatial distribution of the gray pixel intensities as calculated by the co-occurrence features. PMID- 27549347 TI - Role of the metal cation types around VO4 groups on the nonlinear optical behavior of materials: experimental and theoretical analysis. AB - In order to explore new NLO crystals with superior performances, it is greatly desirable to understand the intrinsic relationship between the macroscopic optical properties and microscopic structural features in crystals. A novel mechanism for nonlinear optical (NLO) effects of vanadate crystals, Li3VO4, KCd4(VO4)3 and Ca3(VO4)2 with distorted (VO4)(3-) groups, has been investigated. Experiments related to the synthesis and structures were determined. In addition, infrared and UV-Vis-NIR diffuse reflectance spectroscopy, as well as electronic band structure calculations, were performed on the reported materials. A comprehensive analysis for the structure-property relationship is given by combining the experimental measurements, the electronic structure calculations and the SHG-weighted electron density to the linear and NLO properties. It was found that the contribution of the (VO4)(3-) anionic group to the second harmonic generation (SHG) response was the dominant anionic group, which plays a vital role to the SHG effects in Li3VO4, KCd4(VO4)3 and Ca3(VO4)2. It was also concluded that the metal cation types and coordination around VO4 groups, the distorted and parallel oriented VO4 tetrahedron decided the SHG coefficient values. PMID- 27549348 TI - Incidence of chloramphenicol use and the effect on corneal scrape results in bacterial keratitis. PMID- 27549349 TI - Supramolecular Scaffold for Tailoring the Two-Dimensional Assembly of Functional Molecular Units into Organic Thin Films. AB - Tailoring structurally anisotropic molecular assemblies while controlling their orientation on solid substrates is an important subject for advanced technologies that use organic thin films. Here we report a supramolecular scaffold based on tripodal triptycene assemblies, which enables functional molecular units to assemble into a highly oriented, multilayered two-dimensional (2D) structure on solid substrates. The triptycene building block carries an ethynyl group and three flexible side chains at the 10- and 1,8,13-positions, respectively. These bridgehead-substituted tripodal triptycenes self-assembled on solid substrates to form a well-defined "2D hexagonal + 1D lamellar" structure, which developed parallel to the surface of the substrates. Remarkably, the assembling properties of the triptycene building blocks, particularly for a derivative with tri(oxyethylene)-containing side chains, were not impaired when the alkyne terminal was functionalized with a large molecular unit such as C60, which is comparable in diameter to the triptycene framework. Consequently, thin films with a multilayered 2D assembly of the C60 unit were obtained. Flash-photolysis time resolved microwave conductivity (FP-TRMC) measurements revealed that the C60 film exhibits highly anisotropic charge-transport properties. Bridgehead-substituted tripodal triptycenes may provide a versatile supramolecular scaffold for tailoring the 2D assembly of molecular units into a highly oriented thin film, and in turn for exploiting the full potential of anisotropic molecular functions. PMID- 27549343 TI - Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ~one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2)=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data. PMID- 27549350 TI - Variant rs10911021 that associates with coronary heart disease in type 2 diabetes, is associated with lower concentrations of circulating HDL cholesterol and large HDL particles but not with amino acids. AB - AIMS: An intergenic locus on chromosome 1 (lead SNP rs10911021) was previously associated with coronary heart disease (CHD) in type 2 diabetes (T2D). Using data from the UCLEB consortium we investigated the relationship between rs10911021 and CHD in T2D, whether rs10911021 was associated with levels of amino acids involved in the gamma-glutamyl cycle or any conventional risk factors (CRFs) for CHD in the T2D participants. METHODS: Four UCLEB studies (n = 6531) had rs10911021 imputation, CHD in T2D, CRF and metabolomics data determined using a nuclear magnetic resonance based platform. RESULTS: The expected direction of effect between rs10911021 and CHD in T2D was observed (1377 no CHD/160 CHD; minor allele OR 0.80, 95 % CI 0.60-1.06) although this was not statistically significant (p = 0.13). No association between rs10911021 and CHD was seen in non-T2D participants (11218 no CHD/1274 CHD; minor allele OR 1.00 95 % CIs 0.92-1.10). In T2D participants, while no associations were observed between rs10911021 and the nine amino acids measured, rs10911021 was associated with HDL-cholesterol (p = 0.0005) but the minor "protective" allele was associated with lower levels (-0.034 mmol/l per allele). Focusing more closely on the HDL-cholesterol subclasses measured, we observed that rs10911021 was associated with six large HDL particle measures in T2D (all p < 0.001). No significant associations were seen in non-T2D subjects. CONCLUSIONS: Our findings are consistent with a true association between rs10911021 and CHD in T2D. The protective minor allele was associated with lower HDL-cholesterol and reductions in HDL particle traits. Our results indicate a complex relationship between rs10911021 and CHD in T2D. PMID- 27549351 TI - Examining how p16(INK4a) expression levels are linked to handgrip strength in the elderly. AB - Although many studies have shown that p16(INK4a) is more highly expressed in the human body during senescence, studies on its relevance to handgrip strength among old adults, are relatively sparse. We enrolled 205 community-dwelling old adults aged 65 years and older without specific medical conditions. Handgrip strength of the dominant hand was measured. Low handgrip strength was defined as the lowest quartile of handgrip strength among the participants. RNA was extracted from peripheral white blood cells. Use quantitative polymerase chain reaction to estimate the p16(INK4a) mRNA expression level. The average handgrip strength was 25.22 +/- 8.98 kg, and gender difference was observed. In the linear regression model, the p16(INK4a) mRNA expression level was significantly negatively associated with handgrip strength in men but not in women. The beta coefficient, representing the change of handgrip strength for each increment in the p16(INK4a) mRNA expression level, was -0.208 (p = 0.024) among old men. The negative association remained after additional covariates adjustment. In the multiple logistic regression model among old men, the odds ratio (OR) of low handgrip strength was 1.246 (p = 0.032). In this study, we observed the p16(INK4a) mRNA expression level was negative associated with handgrip strength among community dwelling old men. PMID- 27549352 TI - Deep vein thrombosis in arthroscopic surgery and chemoprophylaxis recommendation in an Asian population. AB - INTRODUCTION: There are currently no guidelines supporting the use of routine chemoprophylaxis to prevent deep vein thrombosis (DVT) in arthroscopic surgery. Studies and meta-analysis show opposing views on its routine use in arthroscopy. This study aimed to examine the incidence of DVT in a prospective cohort of knee arthroscopy and knee arthroplasty patients, and to analyse the risk factors contributing to DVT. METHODS: All patients scheduled to undergo knee arthroscopy or arthroplasty over a two-year period were included. A standardised regimen of postoperative mechanical prophylaxis and rehabilitation was applied to all patients. Only patients who were postoperatively symptomatic were referred for ultrasonography. DVT incidence was calculated, and univariate and multivariate analyses of the risk factors were performed. RESULTS: The overall incidence of DVT was 0.5% among the 1,410 arthroscopy patients and 3.1% among the 802 arthroplasty patients. The incidence of proximal DVT among the arthroscopy and arthroplasty patients was 0.4% and 1.1%, respectively. Multivariate analysis showed that age was the only significant predictor of DVT incidence. Using the receiver operating characteristic method, the cut-off age for the arthroscopy and arthroplasty patients was 52 years, while that for the arthroscopy patients only was 40 years (increased risk of DVT: 5.46 and 6.44 times, respectively; negative predictive value: 99.7% and 99.8%, respectively). CONCLUSION: DVT incidence among Asian arthroplasty and arthroscopy patients remains low, even without chemoprophylaxis. Since age was found to be a significant risk factor for DVT, DVT prophylaxis can be considered for patients in high-risk age groups. PMID- 27549353 TI - Evaluation of Pax5 expression and comparison with BLA.36 and CD79alphacy in feline non-Hodgkin lymphoma. AB - Paired box gene 5 (Pax5) is a widely used B-cell marker for human and canine non Hodgkin's lymphoma (nHL); however, in the literature there is only one case report using Pax5 in a cat B-cell lymphoma. The purposes of this study were to investigate the expression and detection of B-cell specific activator protein (BSAP) using a monoclonal anti-Pax5 antibody in feline nHL (FnHL) tissue samples to evaluate its diagnostic relevance as a B-cell marker. A total of 45 FnHL samples in 45 cats were evaluated. B-cell lymphoma was the most common immunophenotype (51.1%) for all the samples and T-cell the most common immunophenotype (64.3%) for the gastrointestinal (GI) form. Pax5 stained 82.6% of all B-cell lymphomas and no expression was found in any of the T-cell lymphomas. Anti-Pax5 antibody staining in FnHL is similar to that reported in human and canine counterparts and may offer an excellent B-cell marker in cats. PMID- 27549354 TI - The glycemic response to fibre rich foods and their relationship with gastric emptying and motor functions: an MRI study. AB - The chief motor functions of human stomach, namely receiving, storing, mixing and emptying, influence the absorption of ingested food and hence determine the glycemic response to the meal. However, among these functions, the gastric emptying pattern of the stomach is essentially regulated by the meal characteristics such as particle size, volume, nutrient composition and viscosity. Understanding the complex relationship between the stomach motor functions and the physicochemical characteristics of meal on glycemic control needs more attention in the formulation of functional foods. Hence, the objective of this study is to employ the magnetic resonance imaging (MRI) technique in ten healthy human volunteers to elucidate the relationship between the motor functions of the stomach and the glycemic response to fibre rich foods. For this, wheat and oat based breakfast meals were selected as fibre rich foods with low (0.042 Pa s) and high (0.266 Pa s) viscosity, respectively. Although wheat meal had a lower viscosity compared to oatmeal, the gastric emptying was found to be delayed for the former due to its high caloric density. This was reflected in the glycemic response as well, with wheat meal having a lower area under the curve (AUC) value than oatmeal. The antral contraction frequency is significantly reduced (P < 0.05) with delayed gastric emptying in the case of high nutrient wheat meal. Overall, the study demonstrated the synergistic effect of gastric emptying, stomach motor functions and physicochemical characteristics of food on the glycemic response to a meal. This information will aid in the development of functional foods with specific end applications. PMID- 27549356 TI - Prostate cancer: Targeting the ribosome in advanced disease. PMID- 27549355 TI - Integration and utilization of modern technologies in nephrolithiasis research. AB - Nephrolithiasis, or stones, is one of the oldest urological diseases, with descriptions and treatment strategies dating back to ancient times. Despite the enormous number of patients affected by stones, a surprising lack of conceptual understanding of many aspects of this disease still exists. This lack of understanding includes mechanisms of stone formation and retention, the clinical relevance of different stone compositions and that of formation patterns and associated pathological features to the overall course of the condition. Fortunately, a number of new tools are available to assist in answering such questions. New renal endoscopes enable kidney visualization in much higher definition than was previously possible, while micro-CT imaging is the optimal technique for assessment of stone microstructure and mineral composition in a nondestructive fashion. Together, these tools have the potential to provide novel insights into the aetiology of stone formation that might unlock new prevention and treatment strategies, and enable more effective management of patients with nephrolithiasis. PMID- 27549357 TI - Sexual dysfunction: Young at heart? ED linked to CVD. PMID- 27549359 TI - Prostate cancer: Fitting to overcome enzalutamide resistance. PMID- 27549360 TI - Urinary incontinence: Pacing bladder electrical activity. PMID- 27549358 TI - Simulation-based training and assessment in urological surgery. AB - Simulation has become widely accepted as a supplementary method of training. Within urology, the greatest number of procedure-specific models and subsequent validation studies have been carried out in the field of endourology. Many generic-skills simulators have been created for laparoscopic and robot-assisted surgery, but only a limited number of procedure-specific models are available. By contrast, open urological simulation has only seen a handful of validated models. Of the available modalities, virtual reality (VR) simulators are most commonly used for endourology and robotic surgery training, the former also employing many high-fidelity bench models. Smaller dry-lab and ex vivo animal models have been used for laparoscopic and robotic training, whereas live animals and human cadavers are widely used for full procedural training. Newer concepts such as augmented-reality (AR) models and patient-specific simulators have also been introduced. Several curricula, including one recommended within, have been produced, incorporating various different training modalities and nontechnical skills training techniques. Such curricula and validated models should be used in a structured fashion to supplement operating room training. PMID- 27549361 TI - A new era of Asian urology: a SWOT analysis. AB - Economic prosperity and increasing connectivity have made Asia an emerging centre of growth in health care, including in the field of urology. Large and varied patient populations, the availability of a trained workforce, the use of English as a common communication language, and overall low costs have contributed to this change. Rapid growth of regional urological associations and journals has fuelled the aspirations and abilities of Asian urologists to not only keep abreast of but often lead the change in urological disease management. Asian urology has immense potential to expand in areas in which it currently lags behind, the most important being research. The increasing ability to travel aids in developing networks for collaboration. However, Asian urologists will need to look at sustainable models of engagement and temper the need for short-term results if these opportunities are to reach their maximal potential. PMID- 27549362 TI - Redesigning a Participatory Health Study for a French Industrial Context. AB - The Marseille, France, metropolitan area is home to a heavily concentrated industrial region directly adjacent to residential communities. These towns have been subjected to a wide variety of social science and public health studies, but residents continue to have many questions about health concerns for which they currently have primarily anecdotal evidence. Reflecting on our in-progress research in two of these towns, we argue that community-based participatory research that draws from both social science and public health science can be successfully adapted to the French political and cultural context and is key for developing environmental health research that is relevant for community residents and local leaders. Understanding and working within the customs of the local values and practices culture is critical for community-based participatory research regardless of location but is particularly paramount when working in non United States contexts, since local values and practices will shape the particular techniques used within the community-based participatory research framework. PMID- 27549363 TI - The Effect of Fatigue and Fatigue Intensity on Exercise Tolerance in Moderate COPD. AB - INTRODUCTION: Fatigue is one of the most disabling symptoms in COPD, but little is known about the impact of fatigue on functional disability. We explored the impact of fatigue and fatigue intensity on exercise tolerance after adjusting for other factors using multivariate analysis and compared it to that of dyspnoea. METHODS: A total of 119 patients with mainly moderate-severe stable COPD (38 % women, mean age 66 years) were enrolled. We used the Medical Research Council dyspnoea scores (MRC), Manchester COPD fatigue scale (MCFS) and its three dimensions, Borg scales for fatigue and dyspnoea, six-minute walk distance (6MWD), St George's Respiratory Questionnaire, the BODE index, and the Centre for Epidemiological Study on Depression scale (CES-D), and we measured spirometry, blood gases, systemic inflammatory markers and fat-free mass index (FFMI). RESULTS: Fatigue measured using the MCFS was associated with 6MWD and explained 22 % of the variability in 6MWD (p < 0.001). Fatigue remained associated with 6MWD after adjusting for MRC dyspnoea, FFMI and FEV1, FVC, PaO2, PaCO2, CES-D, TNF-alpha, smoking status, age and gender. We found that 33, 50 and 23 % of patients reported an increase by 2 scores on Borg scales for fatigue, dyspnoea or both at the end of the 6MWT. Fatigue scores (both before and after the 6MWT) were negatively correlated with 6MWD after adjusting for FEV1, FFMI, CES-D score and age (p = 0.007 and 0.001, respectively). CONCLUSION: In moderate stable COPD, fatigue may be a central driver of functional disability, to the same extent as dyspnoea. PMID- 27549365 TI - Health effects of 'Juntos', a conditional cash transfer programme in Peru. AB - In some countries, conditional cash transfer (CCT) programmes show an impact on maternal and child health. Juntos, the CCT programme in Peru, has been evaluated several times operationally, but seldom for maternal and child health outcomes. The objective of this study is to evaluate the impact of Juntos on children under 6 years, pregnant women and mothers of children under 17 years. Outcomes evaluated included (1) anaemia in women and children; (2) acute malnutrition in children; (3) post-partum complications in mothers; and (4) underweight and overweight in mothers. We identified Juntos eligible respondents from the Demographic and Health Surveys of Peru for years 2007 to 2013. Propensity score matching was used to identify comparable treatment and control groups, including eligible respondents enrolled in Juntos vs. those not enrolled in Juntos (individual-level analysis), as well as eligible respondents living in Juntos districts vs. those not residing in Juntos districts (district-level analysis). We then used generalized linear models to estimate prevalence ratios. Individual level analysis showed that Juntos reduced underweight in women (PR:0.39, 95%CI:0.18 - 0.85) and anaemia in children (PR:0.93, 95%CI:0.86 - 1.00). In the district level analysis, the programme was associated with a reduction of overweight in women (PR:0.94, 95%CI:0.90 - 0.98) and acute malnutrition in children (PR:0.49, 95%CI:0.32 - 0.73), but an increase in the prevalence of anaemia in children (PR:1.09, 95%CI:1.01 - 1.17). We found that Juntos had an effect on maternal and child health indicators, but further studies are required to overcome some limitations encountered here. PMID- 27549364 TI - Prescription reporting with immediate medication utilization mapping (PRIMUM): development of an alert to improve narcotic prescribing. AB - BACKGROUND: Prescription narcotic overdoses and abuse have reached alarming numbers. To address this epidemic, integrated clinical decision support within the electronic medical record (EMR) to impact prescribing behavior was developed and tested. METHODS: A multidisciplinary Expert Panel identified risk factors for misuse, abuse, or diversion of opioids or benzodiazepines through literature reviews and consensus building for inclusion in a rule within the EMR. We ran the rule "silently" to test the rule and collect baseline data. RESULTS: Five criteria were programmed to trigger the alert; based on data collected during a "silent" phase, thresholds for triggers were modified. The alert would have fired in 21.75 % of prescribing encounters (1.30 % of all encounters; n = 9998), suggesting the alert will have a low prescriber burden yet capture a significant number of at-risk patients. CONCLUSIONS: While the use of the EMR to provide clinical decision support is not new, utilizing it to develop and test an intervention is novel. We successfully built an alert system to address narcotic prescribing by providing critical, objective information at the point of care. The silent phase data were useful to appropriately tune the alert and obtain support for widespread implementation. Future healthcare initiatives can utilize similar methodology to collect data prospectively via the electronic medical record to inform the development, delivery, and evaluation of interventions. PMID- 27549366 TI - A survey of metabolic changes in potato leaves by NMR-based metabolic profiling in relation to resistance to late blight disease under field conditions. AB - Non-targeted nuclear magnetic resonance (NMR)-based metabolic profiling was applied to potato leaves to survey metabolic changes associated with late blight resistance under field conditions. Potato plants were grown in an experimental field, and the compound leaves with no visible symptoms were collected from 20 cultivars/lines at two sampling time points: (i) the time of initial presentation of symptoms in susceptible cultivars and (ii) 12 days before this initiation. 1 H NMR spectra of the foliar metabolites soluble in deuterium oxide- or methanol-d4 based buffers were measured and used for multivariate analysis. Principal component analysis for six cultivars at symptom initiation showed a class separation corresponding to their levels of late blight resistance. This separation was primarily explained by higher levels of malic acid, methanol, and rutin and a lower level of sucrose in the resistant cultivars than in the susceptible ones. Partial least squares regression revealed that the levels of these metabolites were strongly associated with the disease severity measured in this study under field conditions. These associations were observed only for the leaves harvested at the symptom initiation stage, but not for those collected 12 days beforehand. Subsequently, a simple, alternative enzymatic assay for l-malic acid was used to estimate late blight resistance, as a model for applying the potential metabolic marker obtained. This study demonstrated the potential of metabolomics for field-grown plants in combination with targeted methods for quantifying marker levels, moving towards marker-assisted screening of new cultivars with durable late blight resistance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27549367 TI - Metformin - a potentially effective drug for gestational diabetes mellitus: a systematic review and meta-analysis. AB - Metformin has been gradually used in the management of gestational diabetes mellitus (GDM). In order to prove the safety and efficacy of metformin used in pregnancy, we searched several databases for the reports of randomized trials comparing insulin and metformin used in GDM and conducted a meta-analysis. Data showed the rates of neonatal large for gestational age, cesarean section, neonatal respiratory distress and preterm birth were similar in both groups. Maternal glycated hemoglobin-% at gestational week 36-37 was significantly lower in metformin group, indicating good glycemic control of metformin. Maternal weight gain since enrollment to gestational week 36-37 was also lower in metformin group, making metformin worth using even when metformin is insufficient and supplementary insulin is needed. Data also showed that metformin significantly reduced the gestational hypertension complications in GDM patients, probably by reducing the endothelial activation and maternal inflammatory response of insulin resistance. Although metformin can cross the placenta, it is less likely to cause severe neonatal hypoglycemia compared with insulin since it neither stimulates pancreatic insulin release nor increases circulating insulin levels. According to most maternal and neonatal outcomes, metformin is an effective and safe alternative to insulin for GDM patients. PMID- 27549368 TI - Risk of Malignancy in Thyroid Nodules with Non-Diagnostic Fine-Needle Aspiration: A Retrospective Cohort Study. AB - BACKGROUND: Fine-needle aspiration (FNA) of thyroid nodules is commonly performed, and despite the use of ultrasound (US) guidance, the rate of non diagnostic FNAs is still significant. The risk of malignancy of thyroid nodules with a non-diagnostic FNA is not clearly defined. However, most studies exclude the majority of patients without a repeat biopsy or surgery, thus increasing the likelihood of selection bias. The aims of this study were to determine the malignancy risk in nodules with an initial non-diagnostic FNA, and to identify the factors associated with malignancy. METHODS: This was a retrospective cohort study of patients with thyroid nodules who underwent US-guided FNA between 2004 and 2010 and had a non-diagnostic result. Patients were followed until confirmatory diagnosis of the nature of the nodule was made. The outcome of malignant or benign disease was based on one of the following: (i) final surgical pathology following thyroidectomy; (ii) repeat biopsy; (iii) clinically, based on repeat ultrasound performed at least three years following biopsy; or (iv) report of thyroid status for patients without follow-up visits contacted by mail. RESULTS: There were 699 nodules from 665 patients included. The mean age was 59 +/- 15 years, and 71.7% were women. There was complete follow-up of 495 nodules. After a median follow-up of 2.7 years, thyroid cancer was found in 15 nodules. The prevalence of malignancy was 3% (15/495). The presence of nodular calcifications was the strongest predictor of thyroid malignancy (odds ratio 5.03 [confidence interval 1.8-14.7]). Initial nodule size was inversely associated with malignancy (odds ratio 0.55 [confidence interval 0.28-0.93]). However, the 193 patients without follow-up had smaller nodules compared with those included in the analysis. None of the patients with repeatedly non-diagnostic results were diagnosed with thyroid cancer at follow-up. CONCLUSION: The prevalence of thyroid cancer in nodules with non-diagnostic results is lower than the malignancy rate in thyroid nodules in general, but not negligible. They should be followed as per guidelines with heightened suspicion for nodules containing calcifications. Nodules with repeatedly non-diagnostic FNA results especially in the absence of calcifications have a low risk of malignancy and may be observed. PMID- 27549369 TI - The potential impact of bone tissue engineering in the clinic. AB - Bone tissue engineering (BTE) intends to restore structural support for movement and mineral homeostasis, and assist in hematopoiesis and the protective functions of bone in traumatic, degenerative, cancer, or congenital malformation. While much effort has been put into BTE, very little of this research has been translated to the clinic. In this review, we discuss current regenerative medicine and restorative strategies that utilize tissue engineering approaches to address bone defects within a clinical setting. These approaches involve the primary components of tissue engineering: cells, growth factors and biomaterials discussed briefly in light of their clinical relevance. This review also presents upcoming advanced approaches for BTE applications and suggests a probable workpath for translation from the laboratory to the clinic. PMID- 27549370 TI - Transcription-coupled repair: an update. AB - Nucleotide excision repair (NER) is a versatile pathway that removes helix distorting DNA lesions from the genomes of organisms across the evolutionary scale, from bacteria to humans. The serial steps in NER involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. Transcription-coupled repair (TCR) is a subpathway of NER dedicated to the repair of lesions that, by virtue of their location on the transcribed strands of active genes, encumber elongation by RNA polymerases. In this review, I report on recent findings that contribute to the elucidation of TCR mechanisms in the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae and human cells. I review general models for the biochemical pathways and how and when cells might choose to utilize TCR or other pathways for repair or bypass of transcription-blocking DNA alterations. PMID- 27549372 TI - A highly efficient Li2O2 oxidation system in Li-O2 batteries. AB - A novel indirect charging system that uses a redox mediator was demonstrated for Li-O2 batteries. 4-Methoxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl (MeO-TEMPO) was applied as a mediator to enable the oxidation of Li2O2, even though Li2O2 is electrochemically isolated. This system promotes the oxidation of Li2O2 without parasitic reactions attributed to electrochemical charging and reduces the charging time. PMID- 27549371 TI - Higher Order Chromatin Modulator Cohesin SA1 Is an Early Biomarker for Colon Carcinogenesis: Race-Specific Implications. AB - Alterations in high order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer. Cohesins are a family of proteins that modulate high-order chromatin, although the role in colorectal cancer remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in colorectal cancer biology and as a biomarker focusing in particular on the increased incidence/mortality of colorectal cancer among African-Americans. Immunohistochemistry on tissue arrays revealed dramatically decreased SA1 expression in both adenomas (62%; P = 0.001) and adenocarcinomas (75%; P = 0.0001). RT-PCR performed in endoscopically normal rectal biopsies (n = 78) revealed a profound decrease in SA1 expression in adenoma-harboring patients (field carcinogenesis) compared with those who were neoplasia-free (47%; P = 0.03). From a racial perspective, colorectal cancer tissues from Caucasians had 56% higher SA1 expression than in African-Americans. This was mirrored in field carcinogenesis where healthy Caucasians expressed more SA1 at baseline compared with matched African-American subjects (73%; P = 0.003). However, as a biomarker for colorectal cancer risk, the diagnostic performance as assessed by area under ROC curve was greater in African-Americans (AUROC = 0.724) than in Caucasians (AUROC = 0.585). From a biologic perspective, SA1 modulation of high-order chromatin was demonstrated with both biophotonic (nanocytology) and chromatin accessibility [micrococcal nuclease (MNase)] assays in SA1-knockdown HT29 colorectal cancer cells. The functional consequences were underscored by increased proliferation (WST-1; P = 0.0002, colony formation; P = 0.001) in the SA1-knockdown HT29 cells. These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis and as a risk stratification biomarker giving potential insights into biologic basis of racial disparities in colorectal cancer. Cancer Prev Res; 9(11); 844-54. (c)2016 AACR. PMID- 27549373 TI - Endoscopic valve therapy for emphysema: Patient selection as the Holy Grail to success. PMID- 27549374 TI - Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users. AB - Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts structural and functional changes in the human brain. These changes have profound implications for our understanding of the neuropharmacology of cannabis and its effects on cognition, mental health and the brain. PMID- 27549376 TI - Targeting Mitochondria in Cardiovascular Diseases. AB - BACKGROUND: Cardiovascular diseases (CVDs) are one of the main factors responsible for human morbidity and mortality. Since mitochondria play a critical role in the regulation of cardiac tissue homeostasis, this organelle is a critical target for the protective effects of several pharmaceuticals. Although specific mitochondria-targeted antioxidants and some pharmacological agents are described as potential cardioprotective agents, there are still a few effective mitochondrial therapies for the treatment of CVDs. Agents which have potential cardioprotective effects by directly targeting mitochondria in vitro and in vivo are still in pre-clinical or clinical trials, hence their widespread use in the clinic is still far. Also, some of these agents have a decreased bioavailability or show some intrinsic toxicity, which also limits their working mitochondrial concentrations. METHODS: By initially using PubMed specific queries for literature search, we review here cardiac mitochondrial effects of specific targeted and non-targeted antioxidants and pharmacological agents, including MitoE, MitoQ, MitoSNO, Mito-TEMPOL, SkQ1, SkQR1, carvedilol, trimetazidine, ranolazine, diazoxide and propofol. RESULTS: The present review emphasizes new mitochondrial-targeting strategies which have emerged to address difficulties arising from current approaches. We also describe the strengths and weaknesses of these cardioprotective approaches. CONCLUSION: Although effective therapies to target mitochondria in the context of CVDs are not under widespread clinical use, the new strategies proposed constitute a real promise for the development of therapies which may effectively prevent CVDs in the near future. PMID- 27549375 TI - Pharmacological Treatment of Cannabis-Related Disorders: A Narrative Review. AB - BACKGROUND: Cannabis is the most widely used illicit psychoactive substance world wide, yet no medication is approved for the treatment of intoxication, withdrawal, or cannabis use disorder (CUD). OBJECTIVE: To comprehensively review the current state of knowledge. METHOD: Search of the PubMed electronic data base and review of reference lists of relevant articles to identify controlled clinical trials of pharmacological treatment. RESULTS: The search identified 4 trials for specific intoxication symptoms (none for global intoxication), 7 trials for withdrawal, and 12 phase II trials for CUD. One or two trials each suggest that propranolol is effective for some intoxication symptoms, antipsychotics for cannabis-induced psychosis, and dronabinol (synthetic THC) and gabapentin for cannabis withdrawal. Of 10 medications and one medication combination studied in 12 trials for CUD, only two medications were effective (in single trials): gabapentin and Nacetylcysteine (in adolescents). Not effective were dronabinol and several antidepressants, anticonvulsants, and antianxiety medications. Three trials of antidepressants for CUD with comorbid depression gave inconsistent results. A trial of atomoxetine for CUD with comorbid ADHD showed no efficacy. Five trials of second-generation antipsychotics for CUD with comorbid schizophrenia showed none better than any other. CONCLUSION: Further research is needed to confirm the efficacy of gabapentin for withdrawal and gabapentin and N-acetylcysteine for CUD and to develop new medications for all 3 cannabis-related disorders. PMID- 27549377 TI - Effects of Blood Pressure Control in Cardiovascular Prevention. AB - BACKGROUND: High blood pressure is the main risk factor worldwide for mortality and morbidity. Subjects with uncontrolled hypertension increased in the last decades. METHODS: This review is based on the material searched for and obtained via MEDLINE and PubMed up to June 2016. The search terms used were "hypertension, blood pressure control" in combination with "pathophysiology, lifestyle, antihypertensive drugs, target organ damage, target values and comorbidity". RESULTS: This narrative review focused its attention on the diagnosis, the pathophysiology, the clinical consequences of arterial hypertension, and on the factors that must be considered for a better blood pressure control. In fact, the attainment of an adequate blood pressure control is a challenge at both a population and an individual level. CONCLUSION: The review will discuss the best strategy to reduce uncontrolled hypertension and cardiovascular events in hypertensive patients identifying the main conditions which determine and maintain uncontrolled hypertension also highlighting the new possible strategies for a better blood pressure control and including the results of very recent multicenter randomized controlled trials. PMID- 27549378 TI - Cholesterol Lowering Therapy: Treat to Target or Reduce the Global Risk? The Unresolved Problem of Residual Risk. AB - BACKGROUND: Atherosclerotic Cardiovascular Disease (ASCVD) is the first cause of death in Western Countries. Several risk factors contribute to generate atherosclerosis and the preventive therapeutic approaches, in particular statin therapy, reduce the mortality. However, the residual risk in statin treated patients remains significant, despite reaching the low density lipoproteins cholesterol (LDL-C) goals. METHODS: we reviewed the literature published in PUB MED to discuss the role of residual dyslipidemia in particular high density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and lipoprotein(a) [Lp(a)], genetic factors, suboptimal implementation of lifestyle therapy, mood disorders associated to low compliance to application of evidence-based therapies or related to ASCVD. RESULTS: we summarized the current knowledge on the topic, evidencing its contradictory aspects. CONCLUSION: HDL-C is an important biomarker for predicting cardiovascular risk, but the classical HDL hypothesis is no longer correct and it is now being replaced by the HDL function hypothesis, thought more studies are needed to validate it. The connection between cardiovascular risk and levels of TGs is not so definite. APOE genotype and Lp(a) levels are two genetics factors associated to CV risk. Healthy lifestyle with particular dietetic factors, connected to psychological aspects, are very important for the optimal control of the global risk. PMID- 27549379 TI - Cardiovascular Prevention in Obese Patients. AB - BACKGROUND: The World Health Organization has emphasized that an increased body mass index (BMI) is a major risk factor for non-communicable diseases (NCDs) such as cardiovascular disease (CVD) together with diabetes, musculoskeletal disorders and some cancers. The American Heart Association had already identified obesity as an independent risk factor in 1995. There is a significantly increased risk of CVD independently of other traditional risk factors (age, sex, physical activity, smoking, blood pressure and cholesterol levels) for patients fulfilling BMI criteria of moderate overweight, which increases with the diagnosis of obesity. Thus, both overweight and obesity are major risk factors for type 2 diabetes (T2D), hypertension, and atherogenic dyslipidemia, among others. These diseases, when clustered, form the metabolic syndrome, a condition with exponential risk for CVD as compared with its isolated components. In this scenario, obesity emerges as a major public health challenge due to its huge clinical implications, taxing not only individuals but also health-care systems and society at large. METHODS: The present review focuses on: i) the link between dysfunctional fat excess and CVD; ii) the apparent controversies surrounding the obesity paradox as well as the concept of metabolically healthy obesity; iii) the known beneficial effects following weight loss; and iv) available strategies to treat obesity in order to ameliorate cardiovascular risk, which include lifestyle interventions, drug therapy, endoscopic and surgical procedures. CONCLUSION: Obesity is a highly heterogeneous disease that requires customized recommendations. Weight loss in different degrees is attainable via diverse procedures reducing morbidity and mortality while improving psychological well-being and social function. Therapeutic strategies should be tailored to the patient's characteristics and need a long-term personal commitment to change. PMID- 27549380 TI - Targeting Inflammation in Primary Cardiovascular Prevention. AB - BACKGROUND: In the last decade, the development of anti-inflammatory strategies emerged as new trend in cardiovascular (CV) pharmacotherapy. Anti-inflammatory properties have been previously identified in different classes of drugs used in primary CV prevention. However, the extent to which the modification of inflammatory profile contributes in determining CV outcome remains controversial. METHODS: Focusing on potential beneficial effects in primary prevention, this narrative review provides a comprehensive and critical analysis of randomized clinical trials testing anti-inflammatory treatments in CV disease. RESULTS: As upstream regulator of the hepatic production of C-reactive protein, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1 pathways early emerged as potential targets for CV prevention. More recently, additional strategies targeting lipoprotein-associated phospholipase A2, pro-protein convertase subtilisin/kexin type 9, and intracellular pathways (such as p38 MAPK and different isoforms of NADPH oxidase) have been tested. CONCLUSION: Conflicting results emerged from clinical trials, emphasized the need to characterize the inflammatory profile of the patients, to minimize the heterogeneity of study populations and to clarify the true value of CRP as specific biomarker of atherosclerosis-related inflammation. PMID- 27549381 TI - Braddock-Carey syndrome: A 21q22 contiguous gene syndrome encompassing RUNX1. AB - In 1994, Braddock and Carey first reported two unrelated girls with a new multiple malformation syndrome. The primary features included Pierre Robin sequence, persistent neonatal-onset thrombocytopenia, agenesis of the corpus callosum, a distinctive facies, enamel hypoplasia, and severe developmental delay. Since that time, there have been multiple other reported patients with a similar phenotype. In addition, several reports of thrombocytopenia and developmental delay have been documented in association with deletions in the Down syndrome critical region at 21q22. The similarity of the reported cases with deletions involving 21q22 with the clinical presentation of the two patients with Braddock-Carey syndrome resulted in a reinvestigation of the genetic etiology of these two patients 20 years after the original study. This investigation provides evidence that the etiology of this and other "Fanconi-like" disorders represent a newly recognized contiguous gene deletion syndrome involving 21q22 and specifically, the RUNX1 gene. (c) 2016 Wiley Periodicals, Inc. PMID- 27549382 TI - Cost effectiveness of a multi-component school-based physical activity intervention targeting adolescents: the 'Physical Activity 4 Everyone' cluster randomized trial. AB - BACKGROUND: Few school-based interventions have been successful in reducing physical activity decline and preventing overweight and obesity in adolescent populations. As a result, few cost effectiveness analyses have been reported. The aim of this paper is to report the cost and cost effectiveness of the Physical Activity 4 Everyone (PA4E1) intervention which was a multi-component intervention implemented in secondary schools located in low-income communities. Cost effectiveness was assessed using both the physical activity and weight status trial outcomes. METHODS: Intervention and Study Design: The PA4E1 cluster randomised controlled trial was implemented in 10 Australian secondary schools (5 intervention: 5 control) and consisted of intervention schools receiving seven physical activity promotion strategies and six additional strategies that supported school implementation of the intervention components. Costs associated with physical activity strategies, and intervention implementation strategies within the five intervention schools were estimated and compared to the costs of usual physical activity practices of schools in the control group. The total cost of implementing the intervention was estimated from a societal perspective, based on the number of enrolled students in the target grade at the start of the intervention (Grade 7, n = 837). Economic Outcomes: The economic analysis outcomes were cost and incremental cost effectiveness ratios for the following: minutes of moderate-to-vigorous physical activity (MVPA) per day gained, MET hours gained per person/day; Body Mass Index (BMI) unit avoided; and 10% reduction in BMI z-score. RESULTS: The intervention cost AUD $329,952 over 24 months, or AUD$394 per student in the intervention group. This resulted in a cost effectiveness ratio of AUD$56 ($35-$147) per additional minute of MVPA, AUD$1 ($0.6-$2.7) per MET hour gained per person per day, AUD$1408 ($788-$6,570) per BMI unit avoided, and AUD$563 ($282-$3,942) per 10% reduction in BMI z-score. CONCLUSION: PA4E1 is a cost effective intervention for increasing the physical activity levels and reducing unhealthy weight gain in adolescence, a period in which physical activity typically declines. Additional modelling could explore the potential economic impact of the intervention on morbidity and mortality. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000382875. PMID- 27549384 TI - Chemometrics for ion mobility spectrometry data: recent advances and future prospects. AB - Historically, advances in the field of ion mobility spectrometry have been hindered by the variation in measured signals between instruments developed by different research laboratories or manufacturers. This has triggered the development and application of chemometric techniques able to reveal and analyze precious information content of ion mobility spectra. Recent advances in multidimensional coupling of ion mobility spectrometry to chromatography and mass spectrometry has created new, unique challenges for data processing, yielding high-dimensional, megavariate datasets. In this paper, a complete overview of available chemometric techniques used in the analysis of ion mobility spectrometry data is given. We describe the current state-of-the-art of ion mobility spectrometry data analysis comprising datasets with different complexities and two different scopes of data analysis, i.e. targeted and non targeted analyte analyses. Two main steps of data analysis are considered: data preprocessing and pattern recognition. A detailed description of recent advances in chemometric techniques is provided for these steps, together with a list of interesting applications. We demonstrate that chemometric techniques have a significant contribution to the recent and great expansion of ion mobility spectrometry technology into different application fields. We conclude that well thought out, comprehensive data analysis strategies are currently emerging, including several chemometric techniques and addressing different data challenges. In our opinion, this trend will continue in the near future, stimulating developments in ion mobility spectrometry instrumentation even further. PMID- 27549383 TI - Chronic periodontitis can affect the levels of potential oral cancer salivary mRNA biomarkers. AB - BACKGROUND AND OBJECTIVE: More than 100 salivary constituents have been found to show levels significantly different in patients with oral squamous cell carcinoma (OSCC) from those found in healthy controls, and therefore have been suggested to be potential salivary biomarkers for OSCC detection. However, many of these potential OSCC salivary biomarkers are also involved in chronic inflammation, and whether the levels of these biomarkers could be affected by the presence of chronic periodontitis was not known. The objective of this pilot study was therefore to measure the levels of seven previously reported potential OSCC salivary mRNA biomarkers in patients with chronic periodontitis and compare them to levels found in patients with OSCC and healthy controls. The seven salivary mRNAs were interleukin (IL)-8, IL-1beta, dual specificity phosphatase 1, H3 histone family 3A, ornithine decarboxylase antizyme 1, S100 calcium-binding protein P (S100P) and spermidine/spermine N1-acetyltransferase 1. MATERIAL AND METHODS: Unstimulated whole saliva samples were collected from a total of 105 human subjects from the following four study groups: OSCC; CPNS (chronic periodontitis, moderate to severe degree, non-smokers); CPS (chronic periodontitis, moderate to severe degree, smokers); and healthy controls. Levels of each mRNA in patient groups (OSCC or chronic periodontitis) relative to the healthy controls were determined by a pre-amplification reverse transcription quantitative polymerase chain reaction approach with nested gene-specific primers. Results were recorded and analyzed by the Bio-Rad CFX96 Real-Time System. Mean fold changes between each pair of patient vs. control groups were analyzed by the Mann-Whitney U-test with Bonferroni corrections. RESULTS: Only S100P showed significantly higher levels in patients with OSCC compared to both patients with CPNS (p = 0.003) and CPS (p = 0.007). The difference in S100P levels between patients with OSCC and healthy controls was also marginally significant (p = 0.009). There was no significant difference in the levels of salivary IL-8, IL-1beta and dual specificity phosphatase 1 mRNAs between patients with OSCC and patients with CPNS (p = 0.510, 0.058 and 0.078, respectively); no significant difference in levels of salivary ornithine decarboxylase antizyme 1 and spermine N1-acetyltransferase mRNAs between patients with OSCC and patients with CPS (p = 0.318 and 0.764, respectively); and no significant difference in levels of the H3 histone family 3A mRNA between patients with OSCC and either CPS (p = 0.449) or healthy controls (p = 0.107). CONCLUSIONS: Salivary S100P mRNA could be a reliable biomarker for OSCC detection, regardless of the presence of chronic periodontitis. The presence of chronic periodontitis could significantly affect the levels of the other six mRNAs, and negatively influence reliability for using them as biomarkers for oral cancer detection. PMID- 27549385 TI - An Alternative to the Wire Scalpel for Nasolabial Fold Subcision: A Preliminary Study Using a Tuohy Epidural Needle and Vicryl Sutures. AB - BACKGROUND: Subcision techniques involving wire scalpels are used to correct prominent nasolabial folds, depressed scars, and wrinkles. However, these instruments are not universally available. METHODS: We devised a substitute device, consisting of a Tuohy epidural needle and Vicryl sutures, which are easily accessible and inexpensive. We used these novel devices to perform nasolabial fold subcisions in six female patients (mean age 43 years, range 28-65 years) The follow-up period ranged from 4 to 11 months (mean 7 months). RESULTS: Favorable results were obtained for five of six patients, with minimal complications. CONCLUSION: Our subcision technique, employing Tuohy epidural needles and vicryl sutures, was an easy and useful substitute for the use of wire scalpels for improving prominent nasolabial folds. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27549386 TI - A high resolution map of the Arabidopsis thaliana developmental transcriptome based on RNA-seq profiling. AB - Arabidopsis thaliana is a long established model species for plant molecular biology, genetics and genomics, and studies of A. thaliana gene function provide the basis for formulating hypotheses and designing experiments involving other plants, including economically important species. A comprehensive understanding of the A. thaliana genome and a detailed and accurate understanding of the expression of its associated genes is therefore of great importance for both fundamental research and practical applications. Such goal is reliant on the development of new genetic and genomic resources, involving new methods of data acquisition and analysis. We present here the genome-wide analysis of A. thaliana gene expression profiles across different organs and developmental stages using high-throughput transcriptome sequencing. The expression of 25 706 protein-coding genes, as well as their stability and their spatiotemporal specificity, was assessed in 79 organs and developmental stages. A search for alternative splicing events identified 37 873 previously unreported splice junctions, approximately 30% of them occurred in intergenic regions. These potentially represent novel spliced genes that are not included in the TAIR10 database. These data are housed in an open-access web-based database, TraVA (Transcriptome Variation Analysis, http://travadb.org/), which allows visualization and analysis of gene expression profiles and differential gene expression between organs and developmental stages. PMID- 27549388 TI - Differences in Multitask Resource Reallocation After Change in Task Values. AB - OBJECTIVE: The objective was to characterize multitask resource reallocation strategies when managing subtasks with various assigned values. BACKGROUND: When solving a resource conflict in multitasking, Salvucci and Taatgen predict a globally rational strategy will be followed that favors the most urgent subtask and optimizes global performance. However, Katidioti and Taatgen identified a locally rational strategy that optimizes only a subcomponent of the whole task, leading to detrimental consequences on global performance. Moreover, the question remains open whether expertise would have an impact on the choice of the strategy. METHOD: We adopted a multitask environment used for pilot selection with a change in emphasis on two out of four subtasks while all subtasks had to be maintained over a minimum performance. A laboratory eye-tracking study contrasted 20 recently selected pilot students considered as experienced with this task and 15 university students considered as novices. RESULTS: When two subtasks were emphasized, novices focused their resources particularly on one high-value subtask and failed to prevent both low-value subtasks falling below minimum performance. On the contrary, experienced people delayed the processing of one low-value subtask but managed to optimize global performance. CONCLUSION: In a multitasking environment where some subtasks are emphasized, novices follow a locally rational strategy whereas experienced participants follow a globally rational strategy. APPLICATION: During complex training, trainees are only able to adjust their resource allocation strategy to subtask emphasis changes once they are familiar with the multitasking environment. PMID- 27549387 TI - The neuromuscular effects of rocuronium under sevoflurane-remifentanil or propofol-remifentanil anesthesia: a randomized clinical comparative study in an Asian population. AB - BACKGROUND: We conducted a prospective, randomized, multicenter study to evaluate the differences in the blocking effect of different doses of rocuronium between sevoflurane- or propofol-remifentanil anesthesia in an Asian population. METHODS: A total of 368 ASA I-II patients was enrolled. Anesthesia was induced with 2.0 mg/kg propofol and 0.1 MUg/kg/min remifentanil (TIVA) or 5.0 vol.% sevoflurane with 0.1 MUg/kg/min remifentanil (SEVO). Tracheal intubation was facilitated at 180 s after the administration of rocuronium at 0.3, 0.6, or 0.9 mg/kg and then intubation condition was evaluated. The time to maximum block and recovery profile were monitored by TOF stimulation of the ulnar nerve and by recording the adductor pollicis response using acceleromyography. RESULTS: The numbers of patients with clinically acceptable intubation conditions were 41, 82, and 97 % (TIVA) and 34, 85, and 90 % (SEVO) at each dose of rocuronium, respectively. There were no significant differences in the time to maximum block between groups at each rocuronium dose. There were significant differences in the recovery to a train-of-four ratio of 90 % between the groups: 42.7 (19.5), 74.8 (29.9), and 118.4 (35.1) min (TIVA) and 66.5 (39.3), 110.2 (43.5), and 144.4 (57.5) min (SEVO) at 0.3, 0.6, and 0.9 mg/kg, respectively (P < 0.001). CONCLUSIONS: There are no significant differences in intubation conditions between propofol remifentanil and sevoflurane-remifentanil anesthesia at the same dose of rocuronium. The type of anesthetic does not significantly influence the time to maximum block by rocuronium. Rocuronium at a dose of 0.9 mg/kg should be used for better intubation conditions with both anesthesia regimens in an Asian population. TRIAL REGISTRATION: UMIN-CTR Clinical Trial ( http://www.umin.ac.jp/ctr/index.htm ; UMIN#000007289 ; date of registration 14(th) February 2012). PMID- 27549389 TI - Team Training for Dynamic Cross-Functional Teams in Aviation: Behavioral, Cognitive, and Performance Outcomes. AB - OBJECTIVE: This study evaluates the effectiveness of a training program designed to improve cross-functional coordination in airline operations. BACKGROUND: Teamwork across professional specializations is essential for safe and efficient airline operations, but aviation education primarily emphasizes positional knowledge and skill. Although crew resource management training is commonly used to provide some degree of teamwork training, it is generally focused on specific specializations, and little training is provided in coordination across specializations. METHOD: The current study describes and evaluates a multifaceted training program designed to enhance teamwork and team performance of cross functional teams within a simulated airline flight operations center. The training included a variety of components: orientation training, position specific declarative knowledge training, position-specific procedural knowledge training, a series of high-fidelity team simulations, and a series of after action reviews. RESULTS: Following training, participants demonstrated more effective teamwork, development of transactive memory, and more effective team performance. CONCLUSION: Multifaceted team training that incorporates positional training and team interaction in complex realistic situations and followed by after-action reviews can facilitate teamwork and team performance. APPLICATION: Team training programs, such as the one described here, have potential to improve the training of aviation professionals. These techniques can be applied to other contexts where multidisciplinary teams and multiteam systems work to perform highly interdependent activities. PMID- 27549390 TI - Precision breeding for RNAi suppression of a major 4-coumarate:coenzyme A ligase gene improves cell wall saccharification from field grown sugarcane. AB - Sugarcane (Saccharum spp. hybrids) is a major feedstock for commercial bioethanol production. The recent integration of conversion technologies that utilize lignocellulosic sugarcane residues as well as sucrose from stem internodes has elevated bioethanol yields. RNAi suppression of lignin biosynthetic enzymes is a successful strategy to improve the saccharification of lignocellulosic biomass. 4 coumarate:coenzyme A ligase (4CL) is a key enzyme in the biosynthesis of phenylpropanoid metabolites, such as lignin and flavonoids. Identifying a major 4CL involved in lignin biosynthesis among multiple isoforms with functional divergence is key to manipulate lignin biosynthesis. In this study, two full length 4CL genes (Sh4CL1 and Sh4CL2) were isolated and characterized in sugarcane. Phylogenetic, expression and RNA interference (RNAi) analysis confirmed that Sh4CL1 is a major lignin biosynthetic gene. An intragenic precision breeding strategy may facilitate the regulatory approval of the genetically improved events and was used for RNAi suppression of Sh4CL1. Both, the RNAi inducing cassette and the expression cassette for the mutated ALS selection marker consisted entirely of DNA sequences from sugarcane or the sexually compatible species Sorghum bicolor. Field grown sugarcane with intragenic RNAi suppression of Sh4CL1 resulted in reduction of the total lignin content by up to 16.5 % along with altered monolignol ratios without reduction in biomass yield. Mature, field grown, intragenic sugarcane events displayed 52-76 % improved saccharification efficiency of lignocellulosic biomass compared to wild type (WT) controls. This demonstrates for the first time that an intragenic approach can add significant value to lignocellulosic feedstocks for biofuel and biochemical production. PMID- 27549392 TI - Colour coded warnings on how medicines affect driving do not work, study shows. PMID- 27549391 TI - Diagnostic Criteria, Classification and Treatment Goals in Multiple Sclerosis: The Chronicles of Time and Space. AB - Multiple sclerosis (MS) is one of the most diverse human diseases. Since its first description by Charcot in the nineteenth century, the diagnostic criteria, clinical course classification, and treatment goals for MS have been constantly revised and updated to improve diagnostic accuracy, physician communication, and clinical trial design. These changes have improved the clinical outcomes and quality of life for patients with the disease. Recent technological and research breakthroughs will almost certainly further change how we diagnose, classify, and treat MS in the future. In this review, we summarize the key events in the history of MS, explain the reasoning behind the current criteria for MS diagnosis, classification, and treatment, and provide suggestions for further improvements that will keep enhancing the clinical practice of MS. PMID- 27549393 TI - Detecting Protein-Glycolipid Interactions Using Glycomicelles and CaR-ESI-MS. AB - This study reports on the use of the catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay, combined with glycomicelles, as a method for detecting specific interactions between water-soluble proteins and glycolipids (GLs) in aqueous solution. The B subunit homopentamers of cholera toxin (CTB5) and Shiga toxin type 1 B (Stx1B5) and the gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, and GD2 served as model systems for this study. The CTB5 exhibits broad specificity for gangliosides and binds to GM1, GM2, GM3, GD1a, GD1b, and GT1b; Stx1B5 does not recognize gangliosides. The CaR-ESI-MS assay was used to analyze solutions of CTB5 or Stx1B5 and individual gangliosides (GM1, GM2, GM3, GD1a, GD1b, GT1b, and GD2) or mixtures thereof. The high affinity interaction of CTB5 with GM1 was successfully detected. However, the apparent affinity, as determined from the mass spectra, is significantly lower than that of the corresponding pentasaccharide or when GM1 is presented in model membranes such as nanodiscs. Interactions between CTB5 and the low affinity gangliosides GD1a, GD1b, and GT1b, as well as GD2, which served as a negative control, were detected; no binding of CTB5 to GM2 or GM3 was observed. The CaR-ESI-MS results obtained for Stx1B5 reveal that nonspecific protein-ganglioside binding can occur during the ESI process, although the extent of binding varies between gangliosides. Consequently, interactions detected for CTB5 with GD1a, GD1b, and GT1b are likely nonspecific in origin. Taken together, these results reveal that the CaR-ESI-MS/glycomicelle approach for detecting protein-GL interactions is prone to false positives and false negatives and must be used with caution. Graphical Abstract . PMID- 27549394 TI - Influence of the Laser Spot Size, Focal Beam Profile, and Tissue Type on the Lipid Signals Obtained by MALDI-MS Imaging in Oversampling Mode. AB - To improve the lateral resolution in matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) beyond the dimensions of the focal laser spot oversampling techniques are employed. However, few data are available on the effect of the laser spot size and its focal beam profile on the ion signals recorded in oversampling mode. To investigate these dependencies, we produced 2 times six spots with dimensions between ~30 and 200 MUm. By optional use of a fundamental beam shaper, square flat-top and Gaussian beam profiles were compared. MALDI-MSI data were collected using a fixed pixel size of 20 MUm and both pixel-by-pixel and continuous raster oversampling modes on a QSTAR mass spectrometer. Coronal mouse brain sections coated with 2,5-dihydroxybenzoic acid matrix were used as primary test systems. Sizably higher phospholipid ion signals were produced with laser spots exceeding a dimension of ~100 MUm, although the same amount of material was essentially ablated from the 20 MUm-wide oversampling pixel at all spot size settings. Only on white matter areas of the brain these effects were less apparent to absent. Scanning electron microscopy images showed that these findings can presumably be attributed to different matrix morphologies depending on tissue type. We propose that a transition in the material ejection mechanisms from a molecular desorption at large to ablation at smaller spot sizes and a concomitant reduction in ion yields may be responsible for the observed spot size effects. The combined results indicate a complex interplay between tissue type, matrix crystallization, and laser-derived desorption/ablation and finally analyte ionization. Graphical Abstract ?. PMID- 27549395 TI - Activation of Smad2 but not Smad3 is required to mediate TGF-beta signaling during axolotl limb regeneration. AB - Axolotls are unique among vertebrates in their ability to regenerate tissues, such as limbs, tail and skin. The axolotl limb is the most studied regenerating structure. The process is well characterized morphologically; however, it is not well understood at the molecular level. We demonstrate that TGF-beta1 is highly upregulated during regeneration and that TGF-beta signaling is necessary for the regenerative process. We show that the basement membrane is not prematurely formed in animals treated with the TGF-beta antagonist SB-431542. More importantly, Smad2 and Smad3 are differentially regulated post-translationally during the preparation phase of limb regeneration. Using specific antagonists for Smad2 and Smad3 we demonstrate that Smad2 is responsible for the action of TGF beta during regeneration, whereas Smad3 is not required. Smad2 target genes (Mmp2 and Mmp9) are inhibited in SB-431542-treated limbs, whereas non-canonical TGF beta targets (e.g. Mmp13) are unaffected. This is the first study to show that Smad2 and Smad3 are differentially regulated during regeneration and places Smad2 at the heart of TGF-beta signaling supporting the regenerative process. PMID- 27549396 TI - Primary and metastatic tumor dormancy as a result of population heterogeneity. AB - Existence of tumor dormancy, or cancer without disease, is supported both by autopsy studies that indicate presence of microscopic tumors in men and women who die of trauma (primary dormancy), and by long periods of latency between excision of primary tumors and disease recurrence (metastatic dormancy). Within dormant tumors, two general mechanisms underlying the dynamics are recognized, namely, the population existing at limited carrying capacity (tumor mass dormancy), and solitary cell dormancy, characterized by long periods of quiescence marked by cell cycle arrest. Here we focus on mechanisms that precede the avascular tumor reaching its carrying capacity, and propose that dynamics consistent with tumor dormancy and subsequent escape from it can be accounted for with simple models that take into account population heterogeneity. We evaluate parametrically heterogeneous Malthusian, logistic and Allee growth models and show that 1) time to escape from tumor dormancy is driven by the initial distribution of cell clones in the population and 2) escape from dormancy is accompanied by a large increase in variance, as well as the expected value of fitness-determining parameters. Based on our results, we propose that parametrically heterogeneous logistic model would be most likely to account for primary tumor dormancy, while distributed Allee model would be most appropriate for metastatic dormancy. We conclude with a discussion of dormancy as a stage within a larger context of cancer as a systemic disease. REVIEWERS: This article was reviewed by Heiko Enderling and Marek Kimmel. PMID- 27549397 TI - Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis. AB - Addiction is characterized by drug craving, compulsive drug taking and relapse, which is attributed to aberrant neuroadaptation in brain regions implicated in drug addiction, induced by changes in gene and protein expression in these regions after chronic drug exposure. Accumulating evidence suggests that the dorsal hippocampus (DH) plays an important role in mediating drug-seeking and drug-taking behavior and relapse. However, the molecular mechanisms underlying these effects of the DH are unclear. In the present study, we employed a label free quantitative proteomic approach to analyze the proteins altered in the DH of heroin self-administering rats. A total of 4015 proteins were quantified with high confidence, and 361 proteins showed significant differences compared with the saline control group. Among them, cyclin-dependent kinase 5 (CDK5) and ras homolog family member B (RhoB) were up-regulated in rats with a history of extended access to heroin. Functionally, inhibition of CDK5 in the DH enhanced heroin self-administration, indicating that CDK5 signaling in the DH acts as a homeostatic compensatory mechanism to limit heroin-taking behavior, whereas blockade of the Rho-Rho kinase (ROCK) pathway attenuated context-induced heroin relapse, indicating that RhoB signaling in the DH is required for the retrieval (recall) of addiction memory. Our findings suggest that manipulation of CDK5 signaling in the DH may be essential in determining vulnerability to opiate taking, whereas manipulation of RhoB signaling in the DH may be essential in determining vulnerability to relapse. Overall, the present study suggests that the DH can exert dissociative effects on heroin addiction through CDK5 and RhoB signaling. PMID- 27549398 TI - JAGS Evolves: Creating a Proactive Forum. PMID- 27549399 TI - New Psychoactive Substances (NPS) - the Hydra monster of recreational drugs. PMID- 27549400 TI - Enhanced photoelectric conversion efficiency of dye sensitized solar cells via the incorporation of one dimensional luminescent BaWO4:Eu(3+) nanowires. AB - One dimensional hierarchical BaWO4:Eu(3+) nanowires have been prepared via a hydrothermal method for the first time. The obtained BaWO4:Eu(3+) nanowires are not only a promising down-conversion luminescence material, but also can be used to improve the efficiency of dye sensitized solar cells, resulting an efficiency of 7.66%, which is a noticeable enhancement of 15% compared to the cell without BaWO4:Eu(3+) nanowires. We suggest that the enhancement of the efficiencies of the TiO2-BaWO4:Eu(3+) composite cells was mainly related to the light scattering of BaWO4:Eu(3+). PMID- 27549401 TI - Fabrication of pristine Mn2O3 and Ag-Mn2O3 composite thin films by AACVD for photoelectrochemical water splitting. AB - Pristine Mn2O3 and Ag-Mn2O3 composite thin films have been developed on fluorine doped tin oxide (FTO) coated glass substrates at 450 degrees C by aerosol assisted chemical vapor deposition (AACVD) using a methanol solution of a 1 : 2 mixture of acetatoargentate(i), Ag(CH3COO), and a newly synthesized manganese complex, [Mn(dmae)2(TFA)4] (1) (dmae = N,N-dimethylaminoethanolate, TFA = trifluoroacetate). The phase purity and stoichiometric composition of the films were investigated by X-ray diffraction (XRD) and Raman spectroscopy techniques. Energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) analyses revealed a Ag to Mn ratio of 1 : 2 and further confirmed the uniform dispersion of Ag nanoparticles into the Mn2O3 structure. Optical studies showed a direct band gap of 2.0 eV for the pristine Mn2O3 film that was lowered to 1.8 eV for Ag Mn2O3 due to the plasmonic interaction of Ag with Mn2O3. The Ag-Mn2O3 composite film displayed enhanced photocatalytic activity in photoelectrochemical (PEC) water splitting and yielded a photocurrent of 3 mA cm(-2) at 0.7 V versus Ag/AgCl which was 1.6 times higher than a pristine Mn2O3 film alone, under AM 1.5 G illumination (100 mW cm(-2)). The high PEC efficiency is mainly due to the plasmonic effect of Ag nanoparticles, which enhances the visible light absorption, efficient electron-hole separation and high carrier mobility of the Ag-Mn2O3 photoelectrode. The charge carrier density of Ag-Mn2O3 is two times higher than the pristine Mn2O3 as calculated by the Mott-Schottky plot. Based on the PEC studies a mechanism is proposed to elucidate the high activity of Ag Mn2O3 in PEC water splitting. PMID- 27549403 TI - Requirements of Resident Scholarly Activity. PMID- 27549402 TI - Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice. AB - Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning. PMID- 27549404 TI - Antibiotic resistance: mitigation opportunities in livestock sector development. PMID- 27549405 TI - First insights into the nature and evolution of antisense transcription in nematodes. AB - BACKGROUND: The development of multicellular organisms is coordinated by various gene regulatory mechanisms that ensure correct spatio-temporal patterns of gene expression. Recently, the role of antisense transcription in gene regulation has moved into focus of research. To characterize genome-wide patterns of antisense transcription and to study their evolutionary conservation, we sequenced a strand specific RNA-seq library of the nematode Pristionchus pacificus. RESULTS: We identified 1112 antisense configurations of which the largest group represents 465 antisense transcripts (ASTs) that are fully embedded in introns of their host genes. We find that most ASTs show homology to protein-coding genes and are overrepresented in proteomic data. Together with the finding, that expression levels of ASTs and host genes are uncorrelated, this indicates that most ASTs in P. pacificus do not represent non-coding RNAs and do not exhibit regulatory functions on their host genes. We studied the evolution of antisense gene pairs across 20 nematode genomes, showing that the majority of pairs is lineage specific and even the highly conserved vps-4, ddx-27, and sel-2 loci show abundant structural changes including duplications, deletions, intron gains and loss of antisense transcription. In contrast, host genes in general, are remarkably conserved and encode exceptionally long introns leading to unusually large blocks of conserved synteny. CONCLUSIONS: Our study has shown that in P. pacificus antisense transcription as such does not define non-coding RNAs but is rather a feature of highly conserved genes with long introns. We hypothesize that the presence of regulatory elements imposes evolutionary constraint on the intron length, but simultaneously, their large size makes them a likely target for translocation of genomic elements including protein-coding genes that eventually end up as ASTs. PMID- 27549407 TI - Copper(I)-Catalyzed Three-Component Click/Alkynylation: One-Pot Synthesis of 5 Alkynyl-1,2,3-triazoles. AB - A copper(I)-catalyzed tandem CuAAC/alkynylation reaction of various alkynes, organic azides, and bromoalkynes to provide rapid access to 5-alkynyl-1,2,3 triazoles has been developed. The reaction proceeded via a copper-catalyzed alkyne azide cycloaddition followed by interception of the in situ formed cuprate triazole intermediate with bromoalkyne. This reaction offers a new method to afford fully substituted triazoles in high yields with complete regioselectivity under mild reaction conditions. PMID- 27549406 TI - Effect of diagnostic delay on survival in patients with colorectal cancer: a retrospective cohort study. AB - BACKGROUND: Disparate and contradictory results make studies necessary to investigate in more depth the relationship between diagnostic delay and survival in colorectal cancer (CRC) patients. The aim of this study is to analyse the relationship between the interval from first symptom to diagnosis (SDI) and survival in CRC. METHODS: Retrospective study of n = 942 CRC patients. SDI was calculated as the time from the diagnosis of cancer and the first symptoms of CRC. Cox regression was used to estimate five-year mortality hazard ratios as a function of SDI, adjusting for age and gender. SDI was modelled according to SDI quartiles and as a continuous variable using penalized splines. RESULTS: Median SDI was 3.4 months. SDI was not associated with stage at diagnosis (Stage I = 3.6 months, Stage II-III = 3.4, Stage IV = 3.2; p = 0.728). Shorter SDIs corresponded to patients with abdominal pain (2.8 months), and longer SDIs to patients with muchorrhage (5.2 months) and rectal tenesmus (4.4 months). Adjusting for age and gender, in rectum cancers, patients within the first SDI quartile had lower survival (p = 0.003), while in colon cancer no significant differences were found (p = 0.282). These results do not change after adjusting for TNM stage. The splines regression analysis revealed that, for rectum cancer, 5-year mortality progressively increases for SDIs lower than the median (3.7 months) and decreases as the delay increases until approximately 8 months. In colon cancer, no significant relationship was found between SDI and survival. CONCLUSIONS: Short diagnostic intervals are significantly associated with higher mortality in rectal but not in colon cancers, even though a borderline significant effect is also observed in colon cancer. Longer diagnostic intervals seemed not to be associated with poorer survival. Other factors than diagnostic delay should be taken into account to explain this "waiting-time paradox". PMID- 27549408 TI - Antidiarrheal activity of 80 % methanol extract of the aerial part of Ajuga remota Benth (Lamiaceae) in mice. AB - BACKGROUND: In the Ethiopian traditional medicine, the aerial part of Ajuga remota Benth is used in the treatment of diarrhea. There are different mechanisms by which Ajuga remota may have antidiarrheal effect. Some of the possible mechanisms are through its anthelmintic and antibacterial activity. The present study aimed to evaluate whether the antidiarrheal effect of the plant also include antimotility and antisecretory effect using 80 % methanol extract of A. remota (MEAR). METHODS: The MEAR was administered at doses of 200, 400, 600 and 800 mg/kg to four groups of mice (six animals per group) orally in castor oil diarrhea model. The effect of the extract on enteropooling and gastrointestinal transit model was also evaluated using the same grouping and dosing. Two other groups, one as control and the other as standard (loperamide 5 mg/kg) were used for comparison with the treatment groups. RESULTS: The extract at the doses of 400, 600, and 800 mg/kg produced a dose-dependent and significant inhibition both on the frequency and onset of diarrhea. The percentage purging frequency was 53.4, 66.7, 79.6, and 66.7 % (p < 0.001) at three doses of MEAR (400, 600, and 800 mg/kg) and with loperamide (5 mg/kg), respectively. The percentage inhibition in intestinal fluid accumulation was 42.5, 62.1, and 74.2 % (p < 0.001) at the doses of 400, 600 and 800 mg/kg of MEAR, respectively. The MEAR also inhibited the intestinal transit of charcoal meal in a dose dependent manner both in the normal and castor oil induced intestinal transit. CONCLUSION: This study has shown that the 80 % methanol extract of A. remota contains pharmacologically active substances with significant antimotility and antisecretory effect contributing for its antidiarrheal activity. PMID- 27549409 TI - Erratum to: Control of flowering time and spike development in cereals: the earliness per se Eps-1 region in wheat, rice, and Brachypodium. PMID- 27549410 TI - The entangled history of animal and plant microRNAs. AB - MicroRNAs (miRNAs) are small RNAs (sRNAs) that regulate gene expression in development and adaptive responses to the environment. The early days in the sRNA field was one of the most exciting and promising moments in modern biology, attracting large investments to the understanding of the underlining mechanisms and their applications, such as in gene therapy. miRNAs and other sRNAs have since been extensively studied in animals and plants, and are currently well established as an important part of most gene regulatory processes in animals and as master regulators in plants. Here, this review presents the critical discoveries and early misconceptions that shaped our current understanding of RNA silencing by miRNAs in most eukaryotes, with a focus on plant miRNAs. The presentation and language used are simple to facilitate a clear comprehension by researchers and students from various backgrounds. Hence, this is a valuable teaching tool and should also draw attention to the discovery processes themselves, such that scientists from various fields can gain insights from the successful and rapidly evolving miRNA field. PMID- 27549411 TI - Reduction of chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low risk patients. AB - BACKGROUND: Anti-viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis. AIM: To examine the effects of treatment on HCC incidence in CHB with and without cirrhosis, after adjustment for background risks. METHODS: A total of 2255 CHB patients from a US cohort (973 received anti-viral therapy) and 3653 patients from the community-based Taiwanese REVEAL-HBV study, none of whom received treatment. We used Cox proportional hazard models to calculate the risk of developing HCC after adjustment with the previously validated REACH-B risk score. RESULTS: We found 273 incident cases of HCC. After adjustment, therapy lowered the risk of HCC development in the US treated cohort when compared to the US untreated cohort (HR 0.31; 95% CI: 0.15-0.66; P = 0.002). HCC risk reduction was also confirmed when compared to the REVEAL cohort (HR 0.22; 95% CI: 0.12 0.40; P < 0.001). Each REACH-B point was associated with a 53% increased risk of HCC (HR 1.53; 95% CI 1.46-1.59; P < 0.001). We found a significant statistical reduction in HCC incidence with therapy regardless of gender, age, cirrhosis status, HBeAg serology, alanine aminotransferase level, REACH-B score or treatment medication. Therapy was beneficial to those with mildly- to moderately elevated HBV DNA levels (>2000 IU/mL) and of even greater benefit to those with levels >200 000 IU/mL. CONCLUSION: After adjustment for background risk, anti viral therapy was associated with a significant reduction in HCC incidence in both community and real-life clinical cohorts, including in those patients previously thought to be at low risk. PMID- 27549412 TI - Ocular manifestations in leukemia and myeloproliferative disorders and their association with hematological parameters. AB - OBJECTIVES: To study the ocular manifestations in patients diagnosed with leukemia or myeloproliferative disorders and to derive an association between the ocular manifestations and hematological parameters of the patients. MATERIALS AND METHODS: This observational and descriptive study was conducted in a Tertiary Care Center of Dehradun, North India over a period of 1 year. All the diagnosed cases of leukemia and myeloproliferative diseases attending the Oncology Department were included. Patients underwent a detailed ocular examination. The hematological parameters were also recorded including hemoglobin (Hb), total leukocyte count (TLC), and platelet count. RESULTS: The study included 102 patients out of which, there were 66 males (64.7%), and 36 were females (35.3%) with an age range of 5-80 years. A total of forty patients showed ocular manifestations (39.3%). Extraocular manifestations were seen in 10.8% patients while intraocular manifestations were noted in 45.1% patients of acute leukemia and 7.7% patients of chronic leukemia. These ocular manifestations showed a significant association with low Hb (P = 0.000), raised TLC (P = 0.004), and low platelet count (P = 0.000). The most common ocular manifestation was intraretinal hemorrhages followed by roth spots. Among acute myeloid leukemia patients (23.5%), the presence of intraretinal hemorrhages was significantly associated with low Hb (Mann-Whitney U-test = 25.000, P = 0.007). The patients of acute lymphoblastic leukemia (25.4%) showed significant association between intraretinal hemorrhages and low platelet count (Mann-Whitney U-test = 44.000, P = 0.046) and roth spots with low Hb (Mann-Whitney U-test = 11.000, P = 0.000). Ocular manifestations were more commonly seen in acute leukemias as compared to chronic leukemias. CONCLUSION: Ocular examination is recommended in all leukemic patients as ocular manifestations may go unnoticed, most patients being asymptomatic and could be an early sign of worsening of disease. PMID- 27549413 TI - Extending otology services to rural settings: Value of endoscopic ear surgery. AB - INTRODUCTION: Few centers, mainly located in urban settings offer otological surgical services, yet majority of patients requiring these services are rural based and are generally unable to access these centers with resulting disease chronicity and complications. This paper aims to describe the access of otological surgical services by a rural population. METHODOLOGY: This is a retrospective study of patients who accessed otological services at three secondary health institutions and one tertiary referral institution. All patients requiring ear surgery over a 4-year period were studied. The initial 2 years without ear endoscopic surgery was compared with the 2 years when ear endoscopic surgery was introduced. Hospital records were studied and relevant data were extracted. RESULTS: Six hundred and nine ears required surgery over 4 years. Age ranged from 3 to 62 years, with a ratio of 1.4 males: 1 female. During the initial 2 years, all patients were referred from the three secondary health institutions to the urban-based tertiary institution for microscopic ear surgery, 94% failed to proceed on the referral. In the second 2 years, 34% were considered suitable for endoscopic ear surgery, of which 78% accepted and had surgery within the locality. Of the 66% referred, only 5% proceeded on the referral. CONCLUSION: With operator training and investment in portable ear endoscopy set, bulk of ear surgery needing magnification can be treated in the rural setting. This represents a most feasible means of extending the service to the targeted population. PMID- 27549414 TI - Colonoscopy at a tertiary healthcare facility in Southwest Nigeria: Spectrum of indications and colonic abnormalities. AB - BACKGROUND AND AIM: Colonoscopy is considered the gold standard for diagnosing structural colonic diseases. It is safe and effective both for diagnosis and therapeutic interventions. This study was carried out to evaluate the pattern of indications and spectrum of colonic disease at a tertiary healthcare facility in Southwest Nigeria. PATIENTS AND METHODS: All consenting patients who were referred for colonoscopy were recruited into the study. A proforma was used to record information such as biodata of the patients, indications for the procedure, and the findings at colonoscopy. RESULTS: There were 250 patients, comprising 130 (52.0%) males and 120 (48.0%) females, with a male to female ratio of 1.1:1. The mean age of the patients was 57.9 +/- 14.2 years with a range of 15 90 years. The most common indication for colonoscopy was hematochezia 85 (34.0%), others were abdominal pain 46 (18.4%), suspected colonic cancer 27 (10.8%), constipation 27 (10.8%), and chronic diarrhea 22 (8.8%). Sixty-five (26%) patients had normal colonoscopy while various abnormalities were detected in 185 (74%) patients. The most common abnormalities were colonic polyps (23.2%), hemorrhoids (20.8%), diverticulosis (14.8%), colorectal tumor (12.1%), and colitis (4.0%). CONCLUSION: Colonoscopy is an effective means of diagnosing colonic diseases and that the diagnostic yield could be high if the indication were appropriate. The most common indication in our practice was hematochezia, and the most frequent diagnosis was colonic polyps. PMID- 27549415 TI - Induction to delivery interval using transcervical Foley catheter plus oxytocin and vaginal misoprostol: A comparative study at Aminu Kano Teaching Hospital, Kano, Nigeria. AB - BACKGROUND: Induction of labor (IOL) is an artificial initiation of labor before its spontaneous onset for the purpose of delivery of the fetoplacental unit. Many factors are associated with its success in postdatism. OBJECTIVE: To compare the induction delivery intervals using transcervical Foley catheter plus oxytocin and vaginal misoprostol, and to identify the factors associated with successful induction among postdate singleton multiparae. MATERIALS AND METHODS: The study was a prospective randomized controlled trial of singleton multiparous pregnant women. They were randomized into two groups, one group for intravaginal misoprostol and the other group for transcervical Foley catheter insertion as a method of cervical ripening and IOL. The data were analyzed using SPSS version 17 computer software (SPSS Inc., IL, Chicago, USA). Comparisons of categorical variables were done using Chi-squared test, with P < 0.05 considered as significant. Student's t-test was used for continuous variables. RESULTS: The incidence of postdatism was found to be 136 (13.1%). The mean induction delivery time interval was shorter in the misoprostol group 70 (5.54 +/- 1.8 h) than in the Foley catheter oxytocin infusion group 66 (6.65 +/- 1.7 h) (P = 0.035). There was, however, no statistically significant difference in the maternal and neonatal outcomes when these two agents were used for cervical ripening and IOL. Higher parity and higher Bishop's score were the factors found to be associated with high success rate of IOL (P < 0.001). CONCLUSION: Vaginal misoprostol resulted in shorter induction delivery time interval as compared to transcervical Foley catheter. High parity and high Bishop's scores were the factors found to be associated with the success of IOL. PMID- 27549416 TI - Prestroke treatment of stroke risk factors: A cross-sectional survey in central Nigeria. AB - BACKGROUND: Stroke can be prevented with treatments targeted at hypertension, diabetes mellitus, hyperlipidemia and atrial fibrillation, but this is often hampered by under-diagnosis and under-treatment of those risk factors. The magnitude of this problem is not well-studied in sub-Saharan Africa. MATERIALS AND METHODS: We conducted a cross-sectional survey of stroke patients at a tertiary hospital during January 2010 to July 2013 to determine patient awareness of a pre-existing stroke risk factor and prior use of anti-hypertensive, anti diabetic, antiplatelet and lipid-lowering agents. We also investigated whether gender and school education influenced patient awareness and treatment of a stroke risk factor prior to stroke. RESULTS: Three hundred and sixty nine stroke patients presented during the study period, of which 344 eligible subjects were studied. Mean age at presentation (+/-SD) was 55.8 +/- 13.7 years, and was not different for men and women. Hypertension, hyperlipidemia, diabetes and atrial fibrillation were prevalent among 83.7%, 26.5%, 25.6% and 9.6% patients respectively. Awareness was high for pre-existing diabetes (81.8%) and hypertension (76.7%), but not for hyperlipidemia (26.4%) and atrial fibrillation (15.2%). Men were better educated than women (p = 0.002), and had better awareness for hyperlipidemia (37.3% versus 13.5%; p = 0.009). Men were also more likely to take drug treatments for a stroke risk factor, but the differences were significant. CONCLUSIONS: A high rate of under-diagnosis and under-treatment of hypertension, hyperlipidemia and atrial fibrillation contributes to the stroke burden in sub-Saharan Africa, especially among women. Public health measures including mass media campaigns could help reduce the burden of stroke. PMID- 27549417 TI - Epidemiology of congenital anomalies of the central nervous system in children in Enugu, Nigeria: A retrospective study. AB - BACKGROUND: Congenital anomalies, including those of the central nervous system (CNS), are among the leading causes of morbidity, mortality, and fetal loss. OBJECTIVE: To determine the prevalence and associated factors of CNS congenital anomalies in children. METHODS: A cross-sectional retrospective study of children managed with CNS anomalies was undertaken. Relevant clinical data of identified cases based on standard case definitions were retrieved from their case record files. Data were analyzed using SPSS 20.0 while the level of statistical significance was set at P < 0.05. RESULTS: Seventy-two cases of CNS anomalies were identified over the period under review; out of 7329 total pediatric admissions giving a prevalence of 0.98%. Spina bifida cystica, 49 (68.0%) was the most common of the five anomalies seen followed by congenital hydrocephalus 11 (15.3%). Fifty-seven (79.2%) of the mothers did not take periconceptional folic acid supplementation (P < 0.05) whereas 25 (34.7%), 6 (8.3%), and 1 (1.4%) reported history of febrile illness in the first trimester of pregnancy, alcohol use, and diabetes mellitus in pregnancy, respectively. Majority of the cases of spina bifida cystica (30 [61.2%]) seen had corrective surgeries while the overall case fatality rate was 1 (1.4%). CONCLUSIONS: Spina bifida cystica was the most common anomaly of the CNS seen in this study and majority of the mothers of affected children did not take periconceptional folic acid supplementation (P < 0.05). Efforts should be made to create awareness and apply adequate preventive health education models including the use of periconceptional folic acid supplementation as well as the provision of access to standard prenatal care to at risk mothers. PMID- 27549418 TI - Antiphospholipid antibodies among pregnant women with recurrent fetal wastage in a tertiary hospital in Northern Nigeria. AB - CONTEXT: The association between antiphospholipid antibodies (APAs) and pregnancy loss has been established and now considered as a treatable cause of pregnancy loss. Data on the prevalence of APA in patients with recurrent pregnancy loss are scarce in our environment. AIMS: To determine the prevalence of APA in pregnant women with and without recurrent fetal wastage. SETTINGS AND DESIGN: Antenatal clinic of Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. A cross section analytical study. SUBJECTS AND METHODS: Eighty-five antenatal patients with recurrent fetal loss (cases) and an equal number of antenatal patients without recurrent fetal loss (control) matched for age were studied. Their sociodemographic data obtained and blood samples analyzed for lupus anticoagulant (LA) using activated partial thromboplastin time, direct Russel's viper venom time, hexagonal phospholipids, and IgG anticardiolipin antibody (ACA) using enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS USED: Data were analyzed with Statistical Package for Social Sciences (version 17) by univariate analysis and Chi-square test. RESULTS: The age range of the patients was 18-42 years with a median of 30 years. The prevalence of APA was 14.1% and 4.7% among the cases and controls, respectively. The prevalence of LA was 7.1% and 1.2% among the cases and controls, respectively, whereas ACA was 8.2% and 3.5%, respectively. However, one of the cases was positive for both APA and ACA, giving a prevalence of 1.2%. CONCLUSIONS: The prevalence of APA among antenatal patients with recurrent pregnancy loss was, at least, 3 times higher than that of normal antenatal clients. APA should be included in the investigation protocol of women with recurrent fetal wastages in our setting. PMID- 27549419 TI - Cognitive function assessment in patients with end- stage renal disease in Nigeria: A single center experience. AB - AIM: The purpose of this comparative study was to evaluate cognitive function in end-stage renal disease (ESRD) patients in comparison with age, sex, and level of education-matched control. MATERIALS AND METHODS: This is a cross-sectional study involving 80 ESRD patients receiving maintenance hemodialysis treatment and recruited conservatively at the nephrology unit of our hospital. Eighty apparently healthy control, that were matched with the patients for age, sex and education, were also recruited. Following exclusion of depression and severe functional disability, a computer-assisted neuropsychological test, the FePsy, was used to assess memory, psychomotor speed, concentration and attention using simple auditory and visual reaction time tasks, recognition memory tests (RMTs), finger tapping task, and binary choice task (BCT) for both the ESRD patients and controls. RESULTS: ESRD patients performed worse on simple auditory and visual reaction time tasks (P < 0.05), RMTs (P < 0.05), finger tapping task (P < 0.05), BCT, and computerized visual search task (P < 0.05). CONCLUSION: Performance in memory, psychomotor tasks, concentration, and attention tasks were found to be reduced among patients with ESRD compared with age, sex and level of education matched control. PMID- 27549420 TI - Establishing in-hospital geriatrics services in Africa: Insights from the University of Benin Teaching Hospital geriatrics project. AB - BACKGROUND: Unawareness of the peculiar healthcare needs of the elderly and resource constraints may be some reasons why until recently, Nigerian hospitals have not been equipped with the human and infrastructural resources required to meet older adults' special healthcare needs. There is paucity of specialized health services for the elderly in Africa. Nigeria, with a population of over 170 million, did not have any healthcare facility with dedicated services for the elderly until 2012. The University of Benin Teaching Hospital (UBTH) in Nigeria was established in 1973 and created its geriatrics unit in October 2013. A prepared environment and trained interdisciplinary teams are pivotal in providing effective healthcare services for the elderly. The ongoing UBTH geriatrics project aims to provide specialized interdisciplinary health services to older adults and to provide training and continuing professional development in geriatrics for healthcare staff. In developing our inpatient services, we adopted the acute care for elders (ACE) model and worked in tandem with the "ABCs" of implementing ACE units. RESULTS: In the face of limited resources, it was possible to establish a functional geriatrics unit with a trained interdisciplinary team. Family participation is central in our practice. Since October 2013, residents and house officers in internal medicine have been undertaking 4- and 12-weekly rotations, respectively. There is also a robust academic program, which includes once-weekly geriatric pharmacotherapy seminars, once-weekly interdisciplinary seminars, and 2-weekly journal club meetings alternating with seminars on geriatric assessment tools. CONCLUSIONS: It is possible to establish geriatric services and achieve best practices in resource limited settings by investing on improving available human resources and infrastructure. We also make recommendations for setting up similar services in other parts of Africa. PMID- 27549421 TI - Call for global vaccine instead of Helicobacter pylori blind antibiotic therapy. PMID- 27549422 TI - A rapid and versatile method for the isolation, purification and cryogenic storage of Schwann cells from adult rodent nerves. AB - We herein developed a protocol for the rapid procurement of adult nerve-derived Schwann cells (SCs) that was optimized to implement an immediate enzymatic dissociation of fresh nerve tissue while maintaining high cell viability, improving yields and minimizing fibroblast and myelin contamination. This protocol introduces: (1) an efficient method for enzymatic cell release immediately after removal of the epineurium and extensive teasing of the nerve fibers; (2) an adaptable drop-plating method for selective cell attachment, removal of myelin debris, and expansion of the initial SC population in chemically defined medium; (3) a magnetic-activated cell sorting purification protocol for rapid and effective fibroblast elimination; and (4) an optional step of cryopreservation for the storage of the excess of cells. Highly proliferative SC cultures devoid of myelin and fibroblast growth were obtained within three days of nerve processing. Characterization of the initial, expanded, and cryopreserved cell products confirmed maintenance of SC identity, viability and growth rates throughout the process. Most importantly, SCs retained their sensitivity to mitogens and potential for differentiation even after cryopreservation. To conclude, this easy-to-implement and clinically relevant protocol allows for the preparation of expandable homogeneous SC cultures while minimizing time, manipulation of the cells, and exposure to culture variables. PMID- 27549424 TI - CD4+ cell-derived interleukin-17 in a model of dysregulated, Borrelia-induced arthritis. AB - Lyme borreliosis, which is caused in the United States by the spirochete Borrelia burgdorferi, may manifest as different arrays of signs, symptoms and severities between infected individuals. Recent studies have indicated that particularly severe forms of Lyme borreliosis in humans are associated with an increased Th17 response. Here, we hypothesized that a murine model combining the dysregulated immune response of an environment lacking interleukin-10 (IL-10) with a robust T cell-driven inflammatory response would reflect arthritis associated with the production of IL-17 by CD4+ cells. We demonstrate that IL-10 regulates the production of IL-17 by Borrelia-primed CD4+ cells early after interaction with Lyme spirochetes in vitro and that infection of Borrelia-primed mice with B. burgdorferi leads to significant production of IL-17 that contributes to the development of severe arthritis. These results extend our previous findings by demonstrating that a dysregulated adaptive immune response to Lyme spirochetes can contribute to severe, Th17-associated arthritis. These findings may lead to therapeutic measures for individuals with particularly severe symptoms of Lyme borreliosis. PMID- 27549423 TI - 16S rRNA analysis provides evidence of biofilms on all components of three infected periprosthetic knees including permanent braided suture. AB - Bacterial biofilms are the main etiological agent of periprosthetic joint infections (PJI); however, it is unclear if biofilms colonize one or multiple components. Because biofilms can colonize a variety of surfaces, we hypothesized that biofilms would be present on all components. 16S ribosomal RNA (rRNA) gene sequencing analysis was used to identify bacteria recovered from individual components and non-absorbable suture material recovered from three PJI total knee revision cases. Bray-Curtis non-metric multidimensional scaling analysis revealed no significant differences in similarity when factoring component, material type, or suture versus non-suture material, but did reveal significant differences in organism profile between patients (P < 0.001) and negative controls (P < 0.001). Confocal microscopy and a novel agar encasement culturing method also confirmed biofilm growth on a subset of components. While 16S sequencing suggested that the microbiology was more complex than revealed by culture contaminating, bacterial DNA generates a risk of false positives. This report highlights that biofilm bacteria may colonize all infected prosthetic components including braided suture material, and provides further evidence that clinical culture can fail to sufficiently identify the full pathogen profile in PJI cases. PMID- 27549425 TI - Guidelines in review: Comparison of the 2014 ACC/AHA guidelines on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery and the 2014 ESC/ESA guidelines on noncardiac surgery: Cardiovascular assessment and management. PMID- 27549426 TI - 2014 ESC/ESA guidelines on noncardiac surgery: Cardiovascular assessment and management : Are the differences clinically relevant? The USA perspective. PMID- 27549427 TI - Assessment of the area at risk after acute myocardial infarction using 123I-MIBG SPECT: Comparison with the angiographic APPROACH-score. AB - BACKGROUND: Assessment of the area at risk (AAR) associated with an acute myocardial infarction is crucial for evaluating prevention and revascularization strategies. The aim of this study was to evaluate whether 123I metaiodobenzylguanidine (123I-MIBG) single-photon emission computed tomography (SPECT) provides a more widely available assessment of anatomical AAR than the established anatomical angiographic methods. METHODS: Seventy patients with ST segment elevation acute myocardial infarction (STEMI) underwent coronary angiography with percutaneous coronary intervention and subsequent 123I-MIBG myocardial scintigraphy with left myocardial relative radiotracer uptake evaluation 12 +/- 10 days after STEMI. Patients were divided into two groups depending on whether the culprit artery was occluded (50 patients) or sub occluded (20 patients). Two scores were calculated as a percentage of the left ventricular myocardium surface, the first using a standard 17-segment summed rest score derived from the relative quantitative evaluation of 123I-MIBG myocardial uptake (MAR) and the second using the modified APPROACH-score (ApAR). RESULTS: For the patients with occluded artery, this study showed a high correlation between MAR and the angiographic score (Pearson r = .762 and P < .0001). For the patients with sub-occluded artery, for which the ApAR is not reliable, this study showed no correlation between MAR and the angiographic score (Pearson r = .18 and P = 0.45). CONCLUSIONS: 123I-MIBG myocardial scintigraphy provides ARR assessment similar to that of ApAR in patients with a single occluded coronary artery. However, MAR differs from ApAR when angiographic scores are known to be inaccurate (sub-occluded culprit artery) or impossible to use. Further studies are needed to evaluate the potential clinical interest of 123I-MIBG SPECT as an alternative for area at risk assessment after STEMI even when the culprit artery is sub-occluded or when the angiographic scores cannot be used. PMID- 27549428 TI - Serum neutrophil gelatinase-associated lipocalin and resistin are associated with dengue infection in adults. AB - BACKGROUND: Dengue is a major health problem in tropical areas, including Taiwan. Dengue virus infection affects various types of cells and results in elevation of serum inflammatory molecules. Because these molecules may be associated with dengue virus infection, the aim of this study was to identify novel molecules in febrile patients with dengue infection. In addition, we determined whether these molecules were correlated with the count of leukocytes and platelets. METHODS: Febrile adults (Age >18 years old) who presented to the emergency department and were confirmed dengue virus infection were enrolled in this study. Serum from dengue patients and healthy controls was collected and serum level of sepsis associated inflammatory molecules was measured by Luminex assay. RESULTS: Elevated level of macrophage migration inhibitory factor, soluble vascular cell adhesion molecule-1, sFasL, resistin and interferon-gamma were detected in patients' serum. Higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and resistin were detected in dengue patients with normal leukocyte count and all dengue patients, respectively. Furthermore, the serum level of NGAL, but not resistin, was correlated with cell count in dengue patients. CONCLUSION: Our results revealed that resistin and NGAL are novel dengue-associated molecules. These results may help elucidate the regulatory mechanisms of anti-dengue immune responses. PMID- 27549429 TI - Retrospective analysis of the impact of increasing access to long acting reversible contraceptives in a commercially insured population. AB - BACKGROUND: Unintended pregnancies have been shown to be associated with high costs for the healthcare system, among other adverse impacts, but could still account for up to 51 % of pregnancies in the US. Improvements in contraception among women are needed. Long acting reversible contraceptives (LARCs), which have proved their safety and efficacy, have been found to significantly decrease the risk of unintended pregnancy. Yet they are still marginally employed. This study aims at investigating the evolution of LARC use over 15 years and at assessing the impact of the introduction of newer LARCs on LARC use relative to all contraceptive use. METHODS: This retrospective study identified women with LARC or short acting reversible contraceptive (SARC) claims from a US insurance claims database (01/1999-03/2014). Yearly proportions of LARC users relative to all contraceptive users were reported. Generalized estimating equation models were used to assess the impact of user characteristics, such as age group (15-17, 18 24, 25-34, and 35-44), and of time periods related to the introduction of new LARCs (01/2001: Mirena, 07/2006: Implanon, 01/2013: Skyla) on LARC use. RESULTS: A total of 1,040,978 women were selected. LARC use increased yearly from 0.6 % (1999) to 16.6 % (2013) among contraceptive users. Time periods associated with the introduction of a newer LARC were significant predictors of LARC use; women in 2006-2012 and 2013-2014 were respectively 3.7-fold (95 % CI:3.57-3.74) and 6.6 fold (95 % CI:6.43-6.80) more likely to use LARCs over SARCs relative to women in 2001-2006. The increase in LARC use was especially pronounced in young women. Compared to women aged 18-24 in 2001-2006, women aged 18-24 in 2006-2012 and 2013 2014 were respectively 6.4-fold (95 % CI:5.91-6.86) and 14.7-fold (95 % CI:13.59 15.89) more likely to use LARCs over SARCs. CONCLUSIONS: This broadly representative commercial claim-based study showed that the proportion of privately insured women of childbearing age using LARCs increased over time and that the introduction of newer LARCs corresponded with significant increases in overall LARC use. Future research is needed to assess LARC use in uninsured or publicly-insured populations. PMID- 27549430 TI - Acute kidney injury following ingestion of plate developer (sodium metasilicate): a case report. AB - BACKGROUND: Plate developer is a chemical used in the printing industry and is a corrosive alkaline agent containing sodium metasilicate as the main substance. Plate developer poisoning is rare. Literature search revealed only a single case report of fatal sodium metasilicate poisoning (Z Rechtsmed 94(3):245-250, 1985). There are no reports of acute kidney injury related to ingestion of sodium metasilicate containing substances. CASE REPORT: A 52-year-old Sri Lankan male with a history of hypertension and affective disorder presented following ingestion of about 150 ml of plate developer solution. He developed severe upper airway obstruction due to laryngeal edema and underwent tracheostomy. While in the ward he developed features of acute kidney injury with high serum creatinine levels and persistent hyperkalemia which necessitated temporary haemodialysis. Because of the corrosive effect, he developed severe inflammation of the upper gastro intestinal tract with narrowing of esophagus and pyloric region, requiring feeding jejunostomy. He died while waiting for the surgery for pyloric stenosis. CONCLUSIONS: Acute kidney injury is a potential treatable complication of plate developer poisoning other than its complications related to corrosive effects. Regular monitoring of renal functions in such a patient would be useful for early recognition of acute kidney injury. PMID- 27549431 TI - A nurse-coordinated model of care versus usual care for chronic kidney disease: meta-analysis. AB - AIM: To investigate whether a nurse-led care was more beneficial for implementing chronic kidney disease guidelines and improved multiple risk factors compared with the usual care. BACKGROUND: Several independent clinical trials have been carried out to demonstrate the efficiency of a nurse-led care to improve the outcomes for patients with chronic kidney disease and address the risk factors for renal function decline. However, their results and conclusions were inconsistent. METHODS: A meta-analysis was carried out on September 2015 based on previous studies that evaluated the efficiency of nurse-led care model for patients with chronic kidney disease. Following quality appraisal, four randomised clinical trials that allocated patients with chronic kidney disease to usual care and nurse-coordinated care were included. Primary outcomes, such as kidney failure and cardiovascular events, were analysed. RESULTS: Compared with the usual care group, a nurse-coordinated care model reduced the risks of composite death, decreased the occurrence rate of end-stage renal disease and doubled serum creatinine. On the contrary, a slight propulsive effect of nurse led interventional care occurred on acute myocardial infarction and heart failure. LIMITATIONS: Only five studies were included and conducted nonstandard evaluating endpoints, causing fewer studies were categorised in each outcome events in this meta-analysis, subsequently leading to heterogeneity and less persuasive. CONCLUSIONS: Intensive interventions delivered by nurse coordinators are expected to benefit patients to attain longer life expectancy and higher life quality as well as to improve controlling risk factors implicated in chronic kidney disease progression. RELEVANCE TO CLINICAL PRACTICE: More government and hospitals should modify the traditional nursing routine based on this study, providing a more intensive nurse-coaching care model for patients with chronic kidney disease, even aged or other chronic diseases, which shall further help to better control the risk factors and delay disease progression. PMID- 27549432 TI - Azobenzene-derived tris-beta-diketonate lanthanide complexes: reversible trans-to cis photoisomerization in solution and solid state. AB - Novel azobenzene-derived beta-diketonates (4,4,5,5,6,6,6-heptafluoro-1-azobenzene 1,3-hexanedione (LA), 4,4,5,5,6,6,6-heptafluoro-1-(4-dimethylamino)azobenzene-1,3 hexanedione (LB)) were designed and their complexes with lanthanide cations (La(3+), Eu(3+), Gd(3+), Yb(3+)) were prepared and characterized by (1)H NMR, FT IR, and elemental analysis. Three of the complexes were crystallized successfully and identified by X-ray diffraction. It was significant to find that LA showed remarkably reversible trans-to-cis isomerization properties, however, LB, bearing an electron donor compared with LA, slowed down the isomerization to an extent. The presence of Ln(iii) enhanced the reversible trans-to-cis isomerization properties of both LA and LB a little upon photoirradiation in organic solvents, and amazingly increased the fatigue resistance. In addition, the complexes doped in polymethyl methacrylate (PMMA) films produced a similar phenomenon as well as when in solution. Theoretical calculations based on time dependent density functional theory (TD-DFT) were performed for geometry optimization and to determine the excitation energies of LA and LB to gain further insight into the electronic structure of the complexes, and the data were consistent with the experimental results. The excellent reversible photoisomerization properties of the newly designed Ln(iii) complexes can offer important advantages that will help with the further study of these materials to reach their full potential in applications such as molecular switching devices. PMID- 27549433 TI - Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease: A nationwide population-based cohort study. AB - OBJECTIVE: Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate the association between PID and risk of borderline ovarian tumors. METHODS: Using various nationwide Danish registries we identified all women in Denmark during 1978-2012, who were born during 1940-1970 (n=1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. RESULTS: A history of PID was associated with an increased risk of borderline ovarian tumors (HR=1.39; 95% CI: 1.19-1.61). However, histotype specific analyses revealed significant variation in risk as PID was only associated with an increased risk of serous borderline tumors (HR=1.85; 95% CI: 1.52-2.24), but not with mucinous borderline tumors (HR=1.06; 95% CI: 0.83-1.35). CONCLUSIONS: PID is associated with an increased risk of serous borderline tumors. Further research on the potential underlying biological mechanisms and on the identification of the subset of women with PID who are at increased risk of serous borderline tumors is warranted. PMID- 27549434 TI - Investigation of suitable starting doses of narrowband UVB in Asian vitiligo patients: a pilot study. AB - BACKGROUND: Phototherapy is the preferred treatment modality for active and generalized vitiligo. One of the widely accepted consensus on starting dose of phototherapy is using a uniform dose of 280 mJ/cm2 regardless of patients' Fitzpatrick skin phototype (SPT). However, in many clinical experiences with Asian vitiligo patients, the protocol seems suboptimal. OBJECTIVE: To gather more evidence on establishing a higher starting dosage for Asian vitiligo patients undergoing phototherapy. METHODS: We enrolled generalized vitiligo patients with lesions sized adequate enough for phototest. Minimal erythema dose (MED) of vitiligo lesion and non-lesion was measured along with melanin index (MI). RESULTS: Relatively, a wide range of MED and MI was observed even among patients with similar SPT. The range of MED for lesional skin was 300-700 mJ/cm2 and the MED for non-lesion was 500-800 mJ/cm2 . Correlation was noted between lesional MED and non-lesional MI (Spearman correlation, rho = 0.664 [P < 0.036]) and mean lesional MED was approximately 65% of mean non-lesional MED. CONCLUSION: Results from phototest and tolerability of patients to doses higher than 280 mJ/cm2 may indicate that higher starting doses might be appropriate for Asian vitiligo patients. PMID- 27549435 TI - The economic value of INTUITY in aortic valve replacement. AB - OBJECTIVE: The recent development of the EDWARDS INTUITY EliteTM (EIE) valve system enables the rapid deployment of a prosthetic surgical heart valve in an aortic valve replacement (AVR) procedure via both the minimally invasive (MISAVR) and conventional (CAVR) approaches. In order to understand its economic value, this study performed a cost evaluation of the EIE valve system used in a MIS rapid-deployment approach (MIS-RDAVR) vs MISAVR and CAVR, respectively, compared to standard prosthetic aortic valves. METHODS: A simulation model was developed using TreeAge (and validated with MS Excel) to compare the inpatient utilization and complication costs for each treatment arm. Thirty-day clinical end-points for the MIS-RDAVR (mortality and complications) were taken from the TRANSFORM trial; and a best evidence review of the published literature was used for the MISAVR and CAVR approaches. Studies were pooled and parameter estimates were weighted by sample size in order to compare the TRANSFORM patients. Cost data (2016 USD) were taken from the Premier database. Incremental cost and cost-effectiveness was assessed and one-way/probabilistic sensitivity analyses performed to gauge the robustness of the results. RESULTS: MIS-RDAVR costs $2,621 less than CAVR and had lower mortality rates, making it a superior (dominant) technology relative to CAVR. MIS-RDAVR costs $4,560 more than MISAVR, but was associated with an additional 0.20 life years-per-patient. This implies a cost-effectiveness ratio of $22,903 per-life-year-gained. Thus, MIS-RDAVR is cost-effective compared to MISAVR. CONCLUSIONS: The EIE valve system deployed in a MIS approach appears to be a cost-effective technology compared to MISAVR and CAVR. When compared to CAVR it may achieve cost savings as well. These results suggest that MIS-RDAVR confers superior economic value compared to both standard MISAVR and CAVR via lowered key complication rates (re-operation, renal complications, wound infection, TIA, endocarditis) and utilization (cross-clamp time, hospital ward days). PMID- 27549436 TI - Nucleophilic Aromatic Substitution on Pentafluorophenyl-Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy. AB - The application of porphyrinoids in biomedical fields, such as photodynamic therapy (PDT), requires the introduction of functional groups to tune their solubility for the biological environment and to allow a coupling to other active moieties or carrier systems. A valuable motif in this regard is the pentafluorophenyl (PFP) substituent, which can easily undergo a regiospecific nucleophilic replacement (SN Ar) of its para-fluorine atom by a number of nucleophiles. Here, it is shown that, instead of amino-substitution on the final porphyrinoid or BODIPY (boron dipyrromethene), the precursor 5-(PFP)-dipyrrane can be modified with amines (or alcohols). These dipyrranes were transformed into amino-substituted BODIPYs. Condensation of these dipyrranes with aldehydes gave access to trans-A2 B2 -porphyrins and trans-A2 B-corroles. By using pentafluorobenzaldehyde, it was possible to introduce another para-fluorine atom, which enabled the synthesis of multifunctionalized tetrapyrroles. Furthermore, alkoxy- and amino-substituted dipyrranes were applied to the synthesis of A3 B3 hexaphyrins. The polar porphyrins that were prepared by using this method exhibited in vitro PDT activity against several tumor cell lines. PMID- 27549437 TI - Pseudomonas fluorescens C7R12 type III secretion system impacts mycorrhization of Medicago truncatula and associated microbial communities. AB - Type three secretion systems (T3SSs) mediate cell-to-cell interactions between Gram-negative bacteria and eukaryotes. We hypothesized that fluorescent pseudomonads harboring T3SS (T3SS+) would be beneficial to arbuscular mycorrhizal symbiosis because non-pathogenic fluorescent pseudomonads have been previously shown to be much more abundant in mycorrhizal than in non-mycorrhizal roots. We tested this hypothesis by comparing mycorrhization and the associated rhizosphere microbial communities of Medicago truncatula grown in a non-sterile soil inoculated with either the T3SS+ mycorrhiza helper bacterium Pseudomonas fluorescens (C7R12) or a T3SS- mutant of the strain. Results showed that the bacterial secretion system was responsible for the promotion of mycorrhization because root colonization by arbuscular mycorrhizal fungi was not promoted by the T3SS- mutant. The observed T3SS-mediated promotion of mycorrhization was associated with changes in the rhizosphere bacterial communities and the increased occurrence of Claroidoglomeraceae within the intraradical arbuscular mycorrhizal fungi. Furthermore, both pseudomonad strains promoted the host-free growth of a model arbuscular mycorrhizal fungus in vitro, suggesting that T3SS mediated promotion of mycorrhization occurs during plant-fungal interactions rather than during the pre-symbiotic phase of fungal growth. Taken together, these data provide evidence for the involvement of T3SS in promoting arbuscular mycorrhization by a model fluorescent pseudomonad and suggest the implication of interactions between the bacterium and mycorrhizas. PMID- 27549438 TI - Monitoring CO2 emissions to gain a dynamic view of carbon allocation to arbuscular mycorrhizal fungi. AB - Quantification of carbon (C) fluxes in mycorrhizal plants is one of the important yet little explored tasks of mycorrhizal physiology and ecology. 13CO2 pulse chase labelling experiments are increasingly being used to track the fate of C in these plant-microbial symbioses. Nevertheless, continuous monitoring of both the below- and aboveground CO2 emissions remains a challenge, although it is necessary to establish the full C budget of mycorrhizal plants. Here, a novel CO2 collection system is presented which allows assessment of gaseous CO2 emissions (including isotopic composition of their C) from both belowground and shoot compartments. This system then is used to quantify the allocation of recently fixed C in mycorrhizal versus nonmycorrhizal Medicago truncatula plants with comparable biomass and mineral nutrition. Using this system, we confirmed substantially greater belowground C drain in mycorrhizal versus nonmycorrhizal plants, with the belowground CO2 emissions showing large variation because of fluctuating environmental conditions in the glasshouse. Based on the assembled 13C budget, the C allocation to the mycorrhizal fungus was between 2.3% (increased 13C allocation to mycorrhizal substrate) and 2.9% (reduction of 13C allocation to mycorrhizal shoots) of the plant gross photosynthetic production. Although the C allocation to shoot respiration (measured during one night only) did not differ between the mycorrhizal and nonmycorrhizal plants under our experimental conditions, it presented a substantial part (~10%) of the plant C budget, comparable to the amount of CO2 released belowground. These results advocate quantification of both above- and belowground CO2 emissions in future studies. PMID- 27549440 TI - Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32-q27.2. AB - Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32. PMID- 27549439 TI - An assessment of ectomycorrhizal fungal communities in Tasmanian temperate high altitude Eucalyptus delegatensis forest reveals a dominance of the Cortinariaceae. AB - Fungal diversity of Australian eucalypt forests remains underexplored. We investigated the ectomycorrhizal (EcM) fungal community characteristics of declining temperate eucalypt forests in Tasmania. Within this context, we explored the diversity of EcM fungi of two forest types in the northern highlands in the east and west of the island. We hypothesised that EcM fungal community richness and composition would differ between forest type but that the Cortinariaceae would be the dominant family irrespective of forest type. We proposed that EcM richness would be greater in the wet sclerophyll forest than the dry sclerophyll forest type. Using both sporocarps and EcM fungi from root tips amplified by PCR and sequenced in the rDNA ITS region, 175 EcM operational taxonomic units were identified of which 97 belonged to the Cortinariaceae. The Cortinariaceae were the most diverse family, in both the above and below ground communities. Three distinct fungal assemblages occurred within the wet and dry sclerophyll forest types and two geographic regions that were studied, although this pattern did not remain when only the root tip data were analysed. EcM sporocarp richness was unusually higher than root tip richness and EcM richness did not significantly differ among forest types. The results are discussed in relation to the importance of the Cortinariaceae and the drivers of EcM fungal community composition within these forests. PMID- 27549441 TI - Effects of nitrogen availability on polymalic acid biosynthesis in the yeast-like fungus Aureobasidium pullulans. AB - BACKGROUND: Polymalic acid (PMA) is a novel polyester polymer that has been broadly used in the medical and food industries. Its monomer, L-malic acid, is also a potential C4 platform chemical. However, little is known about the mechanism of PMA biosynthesis in the yeast-like fungus, Aureobasidium pullulans. In this study, the effects of different nitrogen concentration on cell growth and PMA biosynthesis were investigated via comparative transcriptomics and proteomics analyses, and a related signaling pathway was also evaluated. RESULTS: A high final PMA titer of 44.00 +/- 3.65 g/L (49.9 +/- 4.14 g/L of malic acid after hydrolysis) was achieved in a 5-L fermentor under low nitrogen concentration (2 g/L of NH4NO3), which was 18.3 % higher yield than that obtained under high nitrogen concentration (10 g/L of NH4NO3). Comparative transcriptomics profiling revealed that a set of genes, related to the ribosome, ribosome biogenesis, proteasome, and nitrogen metabolism, were significantly up- or down-regulated under nitrogen sufficient conditions, which could be regulated by the TOR signaling pathway. Fourteen protein spots were identified via proteomics analysis, and were found to be associated with cell division and growth, energy metabolism, and the glycolytic pathway. qRT-PCR further confirmed that the expression levels of key genes involved in the PMA biosynthetic pathway (GLK, CS, FUM, DAT, and MCL) and the TOR signaling pathway (GS, TOR1, Tap42, and Gat1) were upregulated due to nitrogen limitation. Under rapamycin stress, PMA biosynthesis was obviously inhibited in a dose-dependent manner, and the transcription levels of TOR1, MCL, and DAT were also downregulated. CONCLUSIONS: The level of nitrogen could regulate cell growth and PMA biosynthesis. Low concentration of nitrogen was beneficial for PMA biosynthesis, which could upregulate the expression of key genes involved in the PMA biosynthesis pathway. Cell growth and PMA biosynthesis might be mediated by the TOR signaling pathway in response to nitrogen. This study will help us to deeply understand the molecular mechanisms of PMA biosynthesis, and to develop an effective process for the production of PMA and malic acid chemicals. PMID- 27549442 TI - Decreasing Malpractice Claims by Reducing Preventable Perinatal Harm. AB - OBJECTIVE: To evaluate the association of improved patient safety practices with medical malpractice claims and costs in the perinatal units of acute care hospitals. DATA SOURCES: Malpractice and harm data from participating hospitals; litigation records and medical malpractice claims data from American Excess Insurance Exchange, RRG, whose data are managed by Premier Insurance Management Services, Inc. (owned by Premier Inc., a health care improvement company). STUDY DESIGN: A quasi-experimental prospective design to compare baseline and postintervention data. Statistical significance tests for differences were performed using chi-square, Wilcoxon signed-rank test, and t-test. DATA COLLECTION: Claims data were collected and evaluated by experienced senior claims managers through on-site claim audits to evaluate claim frequency, severity, and financial information. Data were provided to the analyzing institution through confidentiality contracts. PRINCIPAL FINDINGS: There is a significant reduction in the number of perinatal malpractice claims paid, losses paid, and indemnity payments (43.9 percent, 77.6 percent, and 84.6 percent, respectively) following interventions to improve perinatal patient safety and reduce perinatal harm. This compares with no significant reductions in the nonperinatal claims in the same hospitals during the same time period. CONCLUSIONS: The number of perinatal malpractice claims and dollar amount of claims payments decreased significantly in the participating hospitals, while there was no significant decrease in nonperinatal malpractice claims activity in the same hospitals. PMID- 27549443 TI - Undergraduate leadership education for dentistry: preparing for practice. PMID- 27549444 TI - Efficiency-Enhanced Planar Perovskite Solar Cells via an Isopropanol/Ethanol Mixed Solvent Process. AB - Solution processable perovskite solar cells traditionally employed isopropanol as the solvent of CH3NH3I in a two-step method. One of the largest issues of this technique is the uncontrollable morphology of the perovskite film. In this study, a homogeneous and dense PbI2 film was prepared by introducing DMSO as an additive into DMF and then reacting the mixture with CH3NH3I dissolved in an isopropanol/ethanol solvent to fabricate high-quality perovskite films. Results revealed that ethanol played a crucial role on morphology and components of perovskite films. When the ratio of isopropanol to ethanol was optimized, a power conversion efficiency of 15.76% was achieved, which was on average ~50% higher than that of PSCs without DMSO and ethanol processing. PMID- 27549494 TI - End-of-Life Discussions with Older Adults. AB - OBJECTIVES: To determine the prevalence of end-of-life (EOL) conversations with older adults. DESIGN: National Health and Aging Trends Study (NHATS), a prospective, longitudinal survey of Medicare beneficiaries. SETTING: Nationally representative. PARTICIPANTS: A sample drawn from Wave 2 of the NHATS. MEASUREMENTS: The main outcome was the report of an EOL planning discussion, based upon the participant's response to the question "Have you talked to anyone about the types of medical treatment you would want or not want if you became seriously ill in the future?" RESULTS: Sixty-one percent of the sample (n = 1,993 individuals, weighted n = 11,123,910) responded that they had discussed EOL treatment preferences with someone. In multivariate regression, factors associated with reporting an EOL discussion included being younger (adjusted odds ratio (AOR) = 1.70, 95% confidence interval (CI) = 1.17-2.47), having more education (high school degree: AOR = 1.45, 95% CI = 1.02-2.07; some college: AOR = 2.03, 95% CI = 1.40-2.95), and having multiple chronic conditions (AOR = 1.25, 95% CI = 1.01-1.55). Black race was associated with lower odds of reporting a discussion (AOR = 0.46, 95% CI = 0.33-0.65). CONCLUSION: Forty percent of a nationally representative sample of Medicare beneficiaries had not discussed their preferences regarding EOL medical treatment. Promoting these conversations in clinical and nonclinical settings will be important to ensure that health care is delivered to individuals in a person-centered manner. PMID- 27549495 TI - Forensic Application of Palatal Rugae in Dental Identification. AB - INTRODUCTION: The palatal rugae are anatomical folds or wrinkles located on the anterior third of the palate behind the incisive papilla on each side of the palatal raphe. The rugae patterns have been studied for various purposes mainly in the field of anthropology, comparative anatomy, genetics, prosthodontics, orthodontics and forensic odontology. This study is aimed to determine the difference in number and pattern of palatal rugae in males and females. METHODS: This is a prospective study in which maxillary impressions of 50 volunteers, 25 males and 25 females were taken and the casts prepared. The boundaries of the rugae were marked with a HB pencil and were observed with a magnifying glass following the classification used by Kapali, et al, (1997). Association between rugae number and sex and rugae shape and sex were tested using two sample unpaired t test. RESULTS: The study revealed significant difference in the pattern of converge rugae which were found to be higher in females than males, however, no statistical significant difference was found in the number of rugae between the two sexes. CONCLUSIONS: The rugae pattern can be an additional method of differentiation between the males and females in conjunction with the other methods used in forensic sciences. PMID- 27549496 TI - Treatment of Chronic Venous Ulcers Using New Four Layers Compressive Bandage Dressing. AB - INTRODUCTION: Lower-extremity ulcers represent the largest group of ulcers presenting to an outpatient department. It is a cumbersome, difficult to treat disease, which causes high morbidity and huge cost for the patient and healthcare system. Current standard treatment includes compression therapy. However, majority of patients need long term treatment with minimal efficacy. Aim of our study is to evaluate efficacy of four layers compressive bandages for the management of chronic venous ulcers. METHODS: In Group A, we have prospectively included 20 patients with chronic venous ulcers on lower limbs for four layers hosiery bandage using Velfour bandage. Other 15 patients, Group B, were treated with conventional wound dressing. Velfour and crepe bandage were done once weekly for three weeks. RESULTS: DVT was cause of chronic venous ulcer in 70% patient in group A and in 73.3% in Group B. Majority of patients were having left sided chronic venous ulcers. The mean duration of the ulcers was 15.6 vs 10.86 months (group A vs. group B). At the end of 3rd week, in 55% wounds in Group A were healed except few big and deep wounds remained. Most of these wounds also became smaller with minimal discharge. Size of wounds significantly decreased in Group A vs. Group B patients (0.7+/-0.81 cm vs. 1.73+/-0.77 cm, p<0.00031). However, cost of treatment in group A remained higher than group B. CONCLUSIONS: Our study has shown that four layer compressive bandage using Velfour is an easy, effective, and reproducible method of treatment for the chronic venous ulcer. PMID- 27549497 TI - Clinicopathological Pattern of Penile Cancer in a Tertiary Care Centre in Nepal. AB - INTRODUCTION: Carcinoma of penis is an uncommon entity. The higher incidence in developing country may be because of poor hygiene, less common practice of circumcision and unsafe sexual practice. Timely diagnosis and intervention gives the patient a chance of cure. Data on penile cancer is sparse from Nepal so treatment of penile cancer in our centre is presented here. METHODS: This was a retrospective cross-sectional study done at Urology unit of Department of Surgery of Tribhuvan University Teaching Hospital, Nepal from November, 2007 to December, 2013. Data was retrieved from case records and those with penile carcinoma were included. Patient demographics, lesion characteristics, mode of treatment with outcome measures were noted and analyzed. RESULTS: Total 17 patients underwent treatment for primary penile lesion. Mean age of the patients was 51.5 years. Penile growth was the most frequent presentation with five patients coming with more than one symptom. The most common site was over glans of penis (n=13) with the mean size of 3.55 cm. Partial penectomy was offered in 16 with one patient undergoing circumcision only. Inguinal lymph node dissection was done in four patients. Squamous cell carcinoma was the histological diagnosis in 15 patients. CONCLUSIONS: Penile carcinoma is primarily a disease of old. Growth over glans penis is the most common presentation and partial penectomy is feasible in most of the patients to allow oncological cure while preserving the organ for its native function. PMID- 27549498 TI - Aerobic Bacteria in the Diaphragmatic Portion of Stethoscope of Medical Professionals of Tertiary Care Hospital. AB - INTRODUCTION: Hospital environment is a reservoir of wide varieties of microorganisms which are frequently reported colonizing in medical equipment. Stethoscopes are essential tools and of universal use in the medical profession, which might be a source of spreading nosocomial infections. This research project was conducted with an aim to assess the presence of aerobic bacteria in the stethoscope of the medical doctors working at Patan Hospital and students of Patan Academy of Health Sciences. METHODS: It is a cross sectional study based on structured questionnaire and sample assessment from the stethoscope of doctors and students of Patan Hospital and Patan Academy of Health Sciences. The stethescopes used by the doctors of five major departments of Patan Hospital and students of clinical years were included in this study. RESULTS: Total of 99 stethoscope owned by different level of professionals (positions) and different departments were examined for bacterial contamination. Out of them, 36 were found to be considerably contaminated. Single strain of bacteria was grown from a single stethoscope. Among them 34 were Gram positive and remaining were Gram negative. Out of 34 gram postive bacteria, 29 were identified as Staphylococcus aureus, six were identified as Coagulase Negative Staphylococcus and remaining were Gram positive bacilli. CONCLUSIONS: There is presence of aerobic bacteria in diaphragmatic portion of stethoscope of medical professional of which the gram positives were the commonest. PMID- 27549499 TI - Does Tranexamic Acid Reduce Perioperative Bleeding in Short Segment Pedicle Screw Fixation in Thoracolumbar Spine Fractures? AB - INTRODUCTION: Blood loss with spinal surgery is common potential cause of morbidity and often requires blood transfusion. Tranexamic acid (TXA), is effective in reducing bleeding in patients undergoing knee arthroplasty. TXA used in spine surgery studies have included different cases leading to inconsistence of surgical procedures. Purpose of this prospective observational study was to examine effect of TXA decreasing bleeding in short segment pedicle screw fixation for thoracolumbar fractures. METHODS: 38 patients' undergoing short segment pedicle screw for thoracolumbar fractures were enrolled in study from July 2011 to August 2013. There were 28 male and 10 female patients, with an average age of 36.5 years. Patients received 10 mg/kg of TXA or a control 30 minutes intravenously before skin incision and 3 hours post-operative and oral medication for three days. Intraoperative bleeding was estimated by weighing surgical sponges, blood collected by suction container and by subtracting all irrigation fluid. Postoperative bleeding was measured from volume in vacuum drainage bag. RESULTS: Twenty (20) patients were in control group and eighteen(18) to TXA group. There were no statistical differences between groups in terms of age, gender, co-morbidities, and operating time, preoperative Hemoglobin, PT and INR. Intra-operative bleeding in TXA group was significant than in control group. Post operative drainage and Hemoglobin in first 48 h was reduced compared with placebo in TXA group. Need for post-operative transfusion was nil in TXA group. CONCLUSIONS: Administration of TXA before surgery significantly reduces perioperative bleeding in patients undergoing short segment pedicle screw fixation for thoracolumbar spine fractures. PMID- 27549500 TI - Estimation of Physiological Cost Index as an Energy Expenditure Index using MacGregor's Equation. AB - INTRODUCTION: Physical activity and energy expenditure can be quantified by measuring heart rate, oxygen uptake and respiratory quotient. The Physiological Cost Index (PCI) proposed by MacGregor is a simple and straightforward method to estimate the energy expenditure index. Here, we aim to estimate the energy expenditure among young Asian population using MacGregor's equation. METHODS: A total of 50 young randomly selected healthy females performed 50m, 100m and 150m walking test at their self-selected preferred speed. The physiological cost index values for 100 m walk at speeds slower and faster than the preferred speed were also obtained. The physiological cost index during exercise was calculated using MacGregor's equation considering heart rate and speed of walking over the varying distances. RESULTS: The PCI values on three different distances are consistent during self selected preferred speed. The PCI estimation on second and third tests for all three distances walked consistently reproducible. However for each distance walked, the first test the PCI was significantly higher than the second and third test values. The PCI values increased significantly when subjects walked either slower (p = 0.02) or faster (p = 0.001) than their normal preferred speed. CONCLUSION: The physiological cost index values were similar for varying distances walks. The PCI was the least at the preferred speed of walking and increased when the subjects either walked slower or faster than the preferred speed. The first estimation was higher than subsequent estimations. PMID- 27549501 TI - Length of Stay of Orthopaedic Inpatients at a Teaching Hospital in Eastern Part of Nepal. AB - INTRODUCTION: This study aimed to analyze the average length of stay of all inpatients in the department of Orthopaedics and to compare the variations in hospital stay between age, gender, traumatic and non-traumatic co-morbidities and modality of payment. METHODS: This hospital based retrospective descriptive epidemiological study was based on patients discharged from a tertiary level health care center of eastern Nepal. Registry data of 1 year was used to calculate length of stay and analyze the variations. RESULTS: Average length of stay was 10.5 days. It was 10.7 days for males and 10.1 days for females. It was 10.12 days for patients paying themselves for their treatment whereas 14.98 days for patients receiving reimbursement (third party payment). CONCLUSIONS: Average length of stay was more in elderly and patients of trauma (longest in pelvis injury). It was 1.5 times longer for patients receiving reimbursement for treatment. PMID- 27549502 TI - Relationship of Oxygen Saturation with Neonatal and Maternal factors in Vaginal and Cesarean Deliveries. AB - INTRODUCTION: Hypoxemia is the major cause of neonatal morbidity and mortality. The study aims to determine the influence of birth weight, Apgar score, gestation age, body mass index and hemoglobin of mother on levels of SpO2 in healthy newborns born vaginally and through cesarean section. METHODS: A hospital Based, observational study conducted in Department of Pediatrics, Universal College of Medical Sciences-Teaching Hospital, Bhairahawa, Lumbini, Nepal; on 49 vaginal and 49 cesarean deliveries with Apgar Score >= 6. SpO2 was estimated by pulse oximeter post-ductally between 1 to 30 minutes of birth. The observed SpO2 values were correlated with neonatal and maternal factors. RESULTS: Vaginal and Cesarean deliveries SpO2 were comparable for birth weight, gestational age, Apgar score of neonates, body mass index and hemoglobin of the mother. Birth weight in vaginally delivered babies and Apgar score in cesarean births showed significant change in SpO2 (P<0.05). At all points of time the SpO2 values were higher in neonates, born by cesarean than those born out of spontaneous vaginal deliveries (P<0.001). CONCLUSIONS: SpO2 levels in neonates born through cesarean section were higher in comparison to thoseborn by vaginal route. Birth weight and Apgar score had correlation with SpO2 in vaginal and cesarean births, respectively. PMID- 27549503 TI - Visualisation of Rouviere's Sulcus during Laparoscopic Cholecystectomy. AB - INTRODUCTION: Safe dissection of Calot's Triangle is important during the performance of laparascopic cholucystectomy. The purpose of the study is to determine the frequency of demonstrable Rouviere's sulcus in patients with symptomatic gall stones and its role in safe dissection in Calot's triangle. METHODS: This is a prospective descriptive study design done in Department of surgery, Kathmandu Medical College Teaching Hospital from Jan 2013 to Jan 2015. Patients who were posted for laparoscopic cholecystectomy were included. During laparoscopy, Rouviere's sulcus was noted in the operative note and classified according to following: Type I: Open type was defined as a cleft in which the right hepatic pedicle was visualized and the sulcus was opened throughout its length. Type II: if the sulcus was open only at its lateral end. Type III If the sulcus was open only at its medial end. Type IV: Fused type was defined as one in which the pedicle was not visualized. RESULTS: A total of 200 patients underwent laparoscopic cholecystectomy during period of 2 years. Out of which Rouviere's sulcus was visualized in 150 patients (75 %).Type I (open type) was commoner in 54%, type II in 12%, Type III in 9% and type IV (fused type) in 25%. CONCLUSION: Rouviere's Sulcus is an important extra biliary land mark for safe dissection of Calot's triangle during laparoscopic cholecystectomy. KEYWORDS: Rouviere's Sulcus, Laparoscopic cholecystectomy, Bile duct injury. PMID- 27549504 TI - Extracorporeal Irradiation in Malignant Bone Tumors. AB - Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en block removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation and re implantation back in the body. PMID- 27549505 TI - Conventional Brain MRI in Carbon Monoxide Poisoning. AB - Carbon monoxide poisoning is a common fatal condition which can have acute or chronic presentation with varying severity. It commonly involves globus pallidus and putamen but can involve other parts of brain. Conventional MRI using T1 weighted,T2 weighted and FLAIR sequences are helpful in determining the extent of damage to the brain. However, appropriate clinical and laboratory findings should supplement findings on imaging. PMID- 27549506 TI - Extra and Intra-articular Synovial Chondromatosis. AB - Synovial chondromatosis is not so rare intra-articular condition secondary to synovial metaplasia, that affects the knee joint. Extra-articular synovial chondromatosis however is an extremely rare condition that usually involves the synovial sheath or bursa of the foot or hand. We present two cases of synovial chondromatosis, one intra and one extra-articular. The first case was a 25 year old lady who presented with pain, swelling and restricted range of motion of left knee and was found to have an intra-articular synovial chondromatosis which was treated successfully by joint debridement. The second case was that of a 22 year old man who presented with right knee pain and was diagnosed to have an extra articular synovial chondromatosis of his right medial hamstring tendon sheath, excision of which resulted in complete relief of symptoms. PMID- 27549507 TI - Rational for Conducting PTSD Research and Challenges of Recruiting and Training Volunteers to Screen and Treat PTSD among the Nepal 2015 Earthquake Survivors. AB - Post-traumatic Stress Disorder (PTSD) is common psychiatric morbidity among earthquake survivors, and if untreated people suffer from it for years. Government of Nepal and NGOs provided various short-term mental health services to the victims of the 2015 earthquake in Nepal, but there was no plan or provision for long-term mental health problems. The prevalence of PTSD following natural disasters depends on various local factors requiring understanding and further investigation before identifying affordable evidence based interventions. This paper discusses the need for PTSD research among the survivors of the 2015 earthquake in Nepal, and describes the challenges and difficulties of recruiting and training PTSD volunteers. PMID- 27549508 TI - Influence of On-farm pig Salmonella status on Salmonella Shedding at Slaughter. AB - The risk of Salmonella shedding among pigs at slaughter with regard to their previous on-farm Salmonella status was assessed in a group of pigs from a farm from NE of Spain. A total of 202 pigs that had been serologically monitored monthly during the fattening period and from which mesenteric lymph nodes (MLN) and faecal (SFEC) samples were collected at slaughter for Salmonella isolation were included. A repeated-measures anova was used to assess the relationship between mean OD% values during the fattening period and sampling time and bacteriology on MLN and SFEC. Pigs were also grouped into four groups, that is pigs seronegative during the fattening period and Salmonella negative in MLN (group A; n = 69); pigs seronegative during the fattening period but Salmonella positive in MLN (B; n = 36); pigs seropositive at least once and Salmonella positive in MLN (C; n = 50); and pigs seropositive at least once but Salmonella negative in (D; n = 47). Pigs shedding at slaughter seroconverted much earlier and showed much higher mean OD% values than non-shedders pigs. The proportion of Salmonella shedders in groups A and D was high and similar (26.1% and 29.8%, respectively), but significantly lower than that for groups B and C. The odds of shedding Salmonella for groups B and C were 4.8 (95% CI = 1.5-15.5) and 20.9 (3.7 118) times higher, respectively, when compared to A. It was concluded that a large proportion of Salmonella seronegative pigs may shed Salmonella at slaughter, which would be likely associated to previous exposure with contaminated environments (i.e. transport and lairage). For pigs already infected at farm, the likelihood of shedding Salmonella was much higher and may depend on whether the bacterium has colonized the MLN or not. The odds of shedding Salmonella spp. were always much higher for pigs in which Salmonella was isolated from MLN. PMID- 27549509 TI - Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer. AB - BACKGROUND: Many patients with limited disease small cell lung cancer (LD SCLC) suffer from comorbidity. Not all patients with comorbidity are offered standard treatment, though there is little evidence for such a policy. The aim of this study was to investigate whether patients with comorbidity had inferior outcomes in a LD SCLC cohort. MATERIAL AND METHODS: We analyzed patients from a randomized study comparing two three-week schedules of thoracic radiotherapy (TRT) plus standard chemotherapy in LD SCLC. Patients were to receive four courses of cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). Responders received prophylactic cranial irradiation (PCI). Comorbidity was assessed using the Charlson Comorbidity Index (CCI), which rates conditions with increased one-year mortality. RESULTS: In total 157 patients were enrolled between May 2005 and January 2011. Median age was 63 years, 52% were men, 16% had performance status 2, and 72% stage III disease. Forty percent had no comorbidity; 34% had CCI-score 1; 15% CCI 2; and 11% CCI 3 5. There were no significant differences in completion rates of chemotherapy, TRT or PCI across CCI-scores; or any significant differences in the frequency of grade 3-5 toxicity (p = 0.49), treatment-related deaths (p = 0.36), response rates (p = 0.20), progression-free survival (p = 0.18) or overall survival (p = 0.09) between the CCI categories. CONCLUSION: Patients with comorbidity completed and tolerated chemo-radiotherapy as well as other patients. There were no significant differences in response rates, progression-free survival or overall survival - suggesting that comorbidity alone is not a reason to withhold standard therapy in LD SCLC. PMID- 27549510 TI - The burden of hypoxic-ischaemic encephalopathy in Malaysian neonatal intensive care units. AB - INTRODUCTION: This study aimed to determine the incidence of hypoxic-ischaemic encephalopathy (HIE) and predictors of HIE mortality in Malaysian neonatal intensive care units (NICUs). METHODS: This was a retrospective study of data from 37 NICUs in the Malaysian National Neonatal Registry in 2012. All newborns with gestational age >= 36 weeks, without major congenital malformations and fulfilling the criteria of HIE were included. RESULTS: There were 285,454 live births in these hospitals. HIE was reported in 919 newborns and 768 of them were inborn, with a HIE incidence of 2.59 per 1,000 live births/hospital (95% confidence interval [CI] 2.03, 3.14). A total of 144 (15.7%) affected newborns died. Logistic regression analysis showed that the significant predictors of death were: chest compression at birth (adjusted odds ratio [OR] 2.27, 95% CI 1.27, 4.05; p = 0.003), being outborn (adjusted OR 2.65, 95% CI 1.36, 5.13; p = 0.004), meconium aspiration syndrome (MAS) (adjusted OR 2.16, 95% CI 1.05, 4.47; p = 0.038), persistent pulmonary hypertension of the newborn (PPHN) (adjusted OR 4.39, 95% CI 1.85, 10.43; p = 0.001), sepsis (adjusted OR 4.46, 95% CI 1.38, 14.40; p = 0.013), pneumothorax (adjusted OR 4.77, 95% CI 1.76, 12.95; p = 0.002) and severe HIE (adjusted OR 42.41, 95% CI 18.55, 96.96; p < 0.0001). CONCLUSION: The incidence of HIE in Malaysian NICUs was similar to that reported in developed countries. Affected newborns with severe grade of HIE, chest compression at birth, MAS, PPHN, sepsis or pneumothorax, and those who were outborn were more likely to die before discharge. PMID- 27549511 TI - In Vitro Biomechanical Testing of the Tube Knot. AB - OBJECTIVE: To compare in vitro biomechanical properties of the tube knot (TB) to a crimp clamp (CC) system, and square knot (SQ) using 3 monofilament materials. STUDY DESIGN: In vitro biomechanical study. SAMPLE POPULATION: Suture loops (n=20 per material/knot construct). METHODS: Monotonic tensile loading (300 mm/min single pull to failure) was performed on knots tied using 3 knots (TB, 5-throw SQ, and CC system) with each of 3 materials (40# Securos(r) nylon, #2 polypropylene, and #2 nylon). Ultimate tensile strength, elongation, and stiffness were measured and compared by sequential 1- and 2-way ANOVA. RESULTS: Ultimate tensile strength was greatest with 40# nylon CC (mean +/- SD, 293.6 +/- 26.2 N), followed by TB (289.8 +/- 9.2 N) and SQ (252.2 +/- 8.5 N) with no significant difference between CC and TB. TB with #2 polypropylene (158.1 +/- 7.4 N) and #2 nylon (126.3 +/- 5.5 N) had significantly greater tensile strength than SQ with #2 polypropylene (143.6 +/- 5.3 N) and #2 nylon (110.7 +/- 6.2 N). Elongation at failure was significantly greater in 40# nylon TB (25.3 +/- 3.2 mm) and SQ (10.8 +/- 1.6 mm) compared to CC (5.3 +/- 1.0 mm). Both material and knotting method had an effect on ultimate tensile strength, elongation at failure, and stiffness, based on 2-way ANOVA. CONCLUSION: Ultimate tensile strength of TB was equivalent to that of CC; however, elongation at failure was greatest for TB, which may be of concern for clinical applications. PMID- 27549512 TI - Sleep Duration and the Risk of Fatty Liver Disease: A Systematic Review and Meta analysis. AB - Recent studies have reported inconsistent results on the association between sleep duration and the risk of fatty liver disease (FLD). Thus, we quantitatively evaluated this association by performing a systematic review and meta-analysis, based on a comprehensive electronic search in databases of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, Wanfangdata and Chinese National Knowledge Infrastructure (CNKI) (updated to April 2016). Multivariate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were extracted and pooled by using a random-effects model. Eight eligible studies involving 97,371 participants were included. We found that neither short nor long sleep duration was significantly related with FLD risk. For short sleep duration, the pooled OR was 1.17 (95% CI = 0.98-1.38), and for long sleep duration, the pooled OR was 1.01 (95% CI = 0.72 1.41). Subgroup analyses by sex, outcome, and exposure reference also did not identify any effect of sleep duration on FLD onset. In summary, our findings suggested that short or long sleep duration was not significantly associated with FLD risk. Further cohort studies with refined designs are still warranted to validate our results. PMID- 27549513 TI - Calibrating the taxonomy of a megadiverse insect family: 3000 DNA barcodes from geometrid type specimens (Lepidoptera, Geometridae). AB - It is essential that any DNA barcode reference library be based upon correctly identified specimens. The Barcode of Life Data Systems (BOLD) requires information such as images, geo-referencing, and details on the museum holding the voucher specimen for each barcode record to aid recognition of potential misidentifications. Nevertheless, there are misidentifications and incomplete identifications (e.g., to a genus or family) on BOLD, mainly for species from tropical regions. Unfortunately, experts are often unavailable to correct taxonomic assignments due to time constraints and the lack of specialists for many groups and regions. However, considerable progress could be made if barcode records were available for all type specimens. As a result of recent improvements in analytical protocols, it is now possible to recover barcode sequences from museum specimens that date to the start of taxonomic work in the 18th century. The present study discusses success in the recovery of DNA barcode sequences from 2805 type specimens of geometrid moths which represent 1965 species, corresponding to about 9% of the 23 000 described species in this family worldwide and including 1875 taxa represented by name-bearing types. Sequencing success was high (73% of specimens), even for specimens that were more than a century old. Several case studies are discussed to show the efficiency, reliability, and sustainability of this approach. PMID- 27549515 TI - Is the Future of Robotic Surgery Mirroring Aviation and the Glass Cockpit? PMID- 27549516 TI - The Neonatal Arterial Switch Operation: How I Teach It. PMID- 27549514 TI - Cinnamomi Cortex (Cinnamomum verum) Suppresses Testosterone-induced Benign Prostatic Hyperplasia by Regulating 5alpha-reductase. AB - Cinnamomi cortex (dried bark of Cinnamomum verum) is an important drug in Traditional Korean Medicine used to improve blood circulation and Yang Qi. Benign prostatic hyperplasia (BPH) is a common chronic disease in aging men. This study was conducted to determine the effect of Cinnamomi cortex water extract (CC) on BPH. BPH was induced by a pre-4-week daily injection of testosterone propionate (TP). Six weeks of further injection with (a) vehicle, (b) TP, (c) TP + CC, (d) TP + finasteride (Fi) was carried on. As a result, the prostate weight and prostatic index of the CC treatment group were reduced. Histological changes including epithelial thickness and lumen area were recovered as normal by CC treatment. The protein expressions of prostate specific antigen, estrogen receptor alpha (ERalpha), androgen receptor (AR), 5alpha-reductase (5AR), and steroid receptor coactivator 1 were suppressed by treatment of CC. Immunohistochemical assays supported the western blot results, as the expressions of AR and ERalpha were down-regulated by CC treatment as well. Further in vitro experiments showed CC was able to inhibit proliferation of RWPE-1 cells by suppressing 5AR and AR. These results all together suggest CC as a potential treatment for BPH. PMID- 27549517 TI - Sanctions for Research Misconduct in Cardiothoracic Surgery Journals. PMID- 27549518 TI - Invited Commentary. PMID- 27549519 TI - Invited Commentary. PMID- 27549520 TI - Invited Commentary. PMID- 27549521 TI - Invited Commentary. PMID- 27549522 TI - Invited Commentary. PMID- 27549523 TI - Invited Commentary. PMID- 27549524 TI - The First Repair of Cor Triatriatum. AB - This article describes the first patient treated surgically for cor triatriatum, and also describes preoperative testing, operative findings, and procedures, as well as follow-up. PMID- 27549525 TI - Reply. PMID- 27549526 TI - A Minimally Invasive Surgery for Thoracic Esophageal Diverticula. PMID- 27549527 TI - Biomechanics of the Thoracic Aorta: Complexity and Reliability. PMID- 27549528 TI - Reply. PMID- 27549529 TI - Does Neoadjuvant Chemotherapy Have a Role in Stage IIIA Lung Cancer Requiring Pneumonectomy? PMID- 27549530 TI - Reply. PMID- 27549531 TI - Reply. PMID- 27549532 TI - The Underrated Effect of Neoadjuvant Therapy Before Pneumonectomy for Stage IIIA Non-Small Cell Lung Cancer. PMID- 27549533 TI - Is Survival Affected by Nodal Upstaging After Lung Cancer Resection or Surgical Approach? PMID- 27549534 TI - Reply. PMID- 27549535 TI - Training for Thoracoscopic Lobectomy. PMID- 27549536 TI - A Permanent Epicardial Pacemaker Lead That Penetrated the Esophageal Wall 26 years After Implantation. AB - We treated a patient in whom a permanent epicardial pacemaker lead penetrated the esophageal wall 26 years after the index pacemaker implantation. A 28-year-old man with loss of appetite and weight loss underwent upper gastrointestinal endoscopy and was found to have a foreign body protruding into the esophagus. Computed tomography revealed an epicardial lead penetrating the esophageal wall. He had undergone pacemaker implantation with permanent epicardial leads when he was 2 years old. The lead was surgically removed. PMID- 27549537 TI - Extracorporeal Membrane Oxygenation Assisted Segmentectomy for Metachronous Lung Cancer After Pneumonectomy. AB - Advances in extracorporeal membrane oxygenation have enabled the facilitation of surgical intervention in patients who may otherwise be considered inoperable using conventional ventilation-for example, the resection of an early stage metachronous lung cancer in a patient who has previously undergone a pneumonectomy for a prior lung cancer. We present one such case: a 52-year-old man who underwent right lower lobe segmentectomy for a second primary lung cancer, 3 years after left pneumonectomy, using extracorporeal membrane oxygenation. To our knowledge, there are no published case reports describing the use of extracorporeal membrane oxygenation in resection of metachronous lung cancer after pneumonectomy. PMID- 27549538 TI - Penetrating Injury of the Heart From a Chronically Migrating Foreign Body. AB - A 46-year-old man experienced a remote unexpected lung injury with a sharp object. The object migrated over the years, penetrating the mediastinal structure, injuring the pericardium and the right-sided chambers of the heart. The injury was complicated by hemodynamic instability and pericardial tamponade. An emergent pericardiocentesis followed by thoracotomy, foreign body extraction, and puncture site closure. This is a very rare case of remote penetrating lung injury with a dormant course. PMID- 27549539 TI - Anomalous Feeding of the Left Upper Lobe. AB - We report the case of a 53-year-old woman who presented with massive hemoptysis. Computed tomographic angiography revealed an anomalous vessel arising from the abdominal aorta, coursing anteriorly and through the diaphragm, and feeding the left upper lobe. At operation the vessel was found to anastomose to the left upper lobe lingula, which contained multiple vascular abnormalities and arteriovenous fistulas. The vessel was ligated, and the affected portion of the left upper lobe was resected. Anomalous systemic arterial supply of an upper lobe is an especially rare form of a Pryce type 1 abnormality. Recognition of these unusual anatomic variants is crucial to successful treatment and avoidance of adverse events. PMID- 27549540 TI - Functional Benefits of Bilateral Emphysema Reduction Surgery in an Adolescent. AB - Acquired emphysema is a rare pathology in pediatrics. We report the case of a patient born at term with a neonatal respiratory distress, which had required mechanical ventilation. She developed gradually chronic obstructive pulmonary disease with severe emphysematous lesions, respiratory failure and functional impairments. Bilateral emphysema resection, performed at 16 years old, allowed major functional benefits at rest and during exercise. We present the results of respiratory functional evaluations, walk tests and maximal exercise tests (including measure of dynamic hyperinflation) before and after surgery, which highlights that surgery is a successful option in the treatment of compressive emphysema in childhood. PMID- 27549541 TI - Refractory Pulmonary Edema Caused by Late Pulmonary Vein Thrombosis After Lung Transplantation: A Rare Adverse Event. AB - After lung transplantation, pulmonary vein thrombosis is a rare, potentially life threatening adverse event arising at the pulmonary venous anastomosis that typically occurs early and presents as graft failure and hemodynamic compromise with an associated mortality of up to 40%. The incidence, presentation, outcomes, and treatment of late pulmonary vein thrombosis remain poorly defined. Management options include anticoagulant agents for asymptomatic clots, and thrombolytic agents or surgical thrombectomy for hemodynamically significant clots. We present a rare case highlighting a delayed presentation of pulmonary vein thrombosis occurring longer than 2 weeks after lung transplantation and manifesting clinically as graft failure secondary to refractory pulmonary edema. The patient was treated successfully with surgical thrombectomy and remains well. We recommend a high index of suspicion of pulmonary vein thrombosis when graft failure after lung transplantation occurs and is not responsive to conventional therapy, and consideration of investigation with transesophageal echocardiography or computed tomography with venous phase contrast in such patients even more than 2 weeks after lung transplantation. PMID- 27549542 TI - An Unusual Case of Needle Embolus Presenting With Delayed Spontaneous Pneumothorax. AB - We report the case of a 39-year-old man presenting with an acute right-sided traumatic pneumothorax secondary to migration of a hypodermic needle fractured during intravenous drug use. We discuss the unusual passage of this foreign body from the left groin to the right ventricular wall and into the mediastinum, ultimately presenting with a right pneumothorax 1 year later. PMID- 27549543 TI - Logistic ex Vivo Lung Perfusion for Hyperimmunized Patients. AB - Hyperimmunized patients have restricted access to lung transplantation because of the low rate of donor lung availability. Sensitization to human leukocyte antigen is associated with acute rejection, allograft dysfunction, and decreased survival. Prospective crossmatching could allow matching a lung graft with the recipient; however, such a strategy would increase graft ischemia, with a worse impact on the long-term results of lung transplantation. We used logistic ex vivo lung perfusion for 3 patients at the Foch Hospital while waiting for a negative result of the prospective crossmatching and then moved forward to lung transplantation. All patients are alive 3 years after bilateral lung transplantation. PMID- 27549544 TI - Left Atrial Appendage Aneurysm. AB - Left atrial appendage aneurysms (LAAA) are extremely rare. This condition is usually diagnosed incidentally or after the occurrence of thrombotic events or cardiac tachyarrhythmias in the second to fourth decades of life. It can predispose to hazardous adverse events, including atrial fibrillation, myocardial infarction, and systemic thromboembolism. We report a case of LAAA in a 68-year old woman presenting with atypical chest pain, exertional dyspnea, and episodes of sudden-onset palpitation. Aneurysmectomy with the patient under cardiac arrest with cardiopulmonary bypass was performed. In addition, we explore the diagnosis, management, and prognosis of this entity through a meticulous literature review. PMID- 27549545 TI - Transcatheter Valve-in-Valve: A Cautionary Tale. AB - Transcatheter aortic valve replacement (TAVR) by valve-in-valve (VIV) implantation is an alternative treatment for high-risk patients with a degenerating aortic bioprosthesis. We present a case of transapical TAVR VIV with a 29-mm Edwards SAPIEN XT (ESV) (Edwards Lifesciences, Irvine, CA) into a 29-mm Medtronic Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, MN) in which unanticipated dilatation of the Freestyle bioprosthesis resulted in intraprocedural embolization of the TAVR valve, necessitating urgent conversion to a conventional surgical aortic valve replacement (AVR). Our experience suggests that TAVR VIV with the 29-mm ESV in the setting of a degenerated 29-mm Freestyle stentless bioprosthesis must be undertaken with caution. PMID- 27549546 TI - Cardiac Paraganglioma Arising From the Right Atrioventricular Groove in a Paraganglioma-Pheochromocytoma Family Syndrome With Evidence of SDHB Gene Mutation: An Unusual Presentation. AB - Primary cardiac paragangliomas are extremely rare. Recently this neoplasm has been associated with a familiar syndrome as a result of mutation of genes that encode proteins in the mitochondrial complex II. We report a case of a 46-year old woman having cases of vertebral paraganglioma in her family showing an unusual anatomic and clinical presentation of cardiac paraganglioma and expressing a genetic mutation never associated before with cardiac localization of this neoplasm. PMID- 27549547 TI - A Rare Case of Mitral Valve Prolapse in Endomyocardial Fibrosis. AB - Mitral valve prolapse in endomyocardial fibrosis (EMF) is an unusual entity. Literature search reveals only 1 report of mitral valve prolapse assosiated with EMF. A 32-year-old woman, of African origin, who presented with features of right heart failure, was diagnosed to have mitral valve prolapse of rheumatic origin with severe mitral regurgitation and severe pulmonary hypertension (PAH). Intraoperative findings lead to the diagnosis of EMF. We report this rare case of mitral valve prolapse in EMF, in a geographical area where rheumatic heart disease is endemic, to showcase how a rare manifestation of EMF can be misdiagnosed as that of rheumatic heart disease. PMID- 27549548 TI - Pulmonary Valve Intimal Sarcoma. AB - Malignant cardiac tumors are very rare. They carry a high risk of morbidity and death. We present a case of malignant intimal sarcoma that originated from the pulmonary valve leaflet in a 72-year-old woman. The clinical presentation was gradual onset of shortness of breath and fatigue.We successfully removed the tumor, with pulmonary valve preservation. PMID- 27549549 TI - Minimally Invasive Periareolar Approach to Unroofed Coronary Sinus Atrial Septal Defect Repair. AB - Less invasive techniques are commonly used to treat patients with anatomically suitable secundum atrial septal defects; however, repair of more complex atrial septal defects are still performed through sternotomy. Cosmetically appealing periareolar incisions have been used in breast reconstructive surgery and may provide an esthetically superior alternative to the anterolateral minithoracotomy incision used in minimally invasive cardiac surgery. We describe a patient with an unroofed coronary sinus atrial septal defect who underwent successful minimally invasive, endoscopic repair of this defect with autologous pericardial baffle reconstruction of the coronary sinus roof and closure of the interatrial communication through a periareolar approach. PMID- 27549550 TI - Successful Re-Repeat Resection of Primary Left Atrial Sarcoma After Previous Tumor Resection and Cardiac Autotransplant Procedures. AB - Primary cardiac sarcomas are rare but aggressive tumors and can present a technical challenge with regard to surgical approach and resection. Complete surgical resection, when feasible, remains crucial for palliation of symptoms and for its role as the mainstay of cardiac sarcoma therapy. Surgical resection of recurrent cardiac sarcomas, though formidable, is technically feasible and may provide reasonable survival, especially when the recurrence is local and the metastatic load is limited. In this case report, we describe a successful third cardiac sarcoma resection procedure in a young patient with previous cardiac autotransplantation and excision of left atrial sarcoma. PMID- 27549551 TI - Accessory Liver in the Right Atrium: A Rare Cause of Syncope. AB - This report highlights the first case of complete resection of an accessory liver found embedded in the right atrium obstructing venous return to the heart, acutely reducing cardiac output, and producing recurrent syncopal episodes. PMID- 27549552 TI - Thoracic Endovascular Stent Graft Repair of Middle Aortic Syndrome. AB - Middle aortic syndrome is a rare disease defined as a segmental narrowing of the distal descending thoracic or abdominal aorta. A thoracoabdominal bypass or endovascular treatment is the choice of treatment. Endovascular therapy consists of a balloon dilatation and stent implantation. Recently, thoracic endovascular aortic repair has been widely used in a variety of aortic diseases. We report a case of middle aortic syndrome treated with a thoracic endovascular stent graft. PMID- 27549553 TI - Pulmonary Venous Obstruction From a Large Left Atrial Sarcoma: Resection Combined With Mitral Valve Bypass. AB - Cardiac sarcomas represent the majority of primary malignant cardiac tumors. They are usually located in the right atrium and are frequently angiosarcomas. We present a case of primary cardiac sarcoma originating from the left atrium in a 40-year-old woman that was treated with resection combined with mitral valve bypass. PMID- 27549554 TI - Modification of a Standard Thoracoabdominal Incision to Preserve Collaterals to Adamkiewicz Artery. AB - We report a case of a 35-year-old male who underwent thoracoabdominal aortic repair of a chronic dissecting aortic aneurysm, Crawford extent II. Preoperative computed tomography showed thrombosis of almost all intercostal arteries. Precise diagnostic assessment demonstrated the Adamkiewicz artery originating from the left lateral thoracic artery and subscapular artery, which would have been at risk after using a standard Stoney's incision, thus potentially causing paraplegia or paraparesis due to spinal cord ischemia. We modified the lateral thoracic incision anteriorly and successfully preserved the collateral arteries without impairing the spinal cord function. PMID- 27549555 TI - Successful Thrombectomy for an Idiopathic Floating Ascending Aortic Thrombus. AB - A mobile thrombus in an otherwise normal ascending aorta is rare, but it should be thoroughly searched for in patients with unexplained cerebral or peripheral embolism. We report the case of a 49-year-old man admitted for right lower quadrant abdominal pain secondary to embolic renal infarction. Echocardiography and computed tomography of the chest revealed a 2.5 cm * 1.5 cm hypermobile mass at the distal ascending aorta, which was otherwise normal. No hypercoagulable condition could be identified. The mass was successfully removed with the patient under deep hypothermic circulatory arrest and was confirmed to be a thrombus. The cause of this thrombus remains unknown. PMID- 27549556 TI - Concealed Left Ventricle to Right Atrium Fistula Complicating Infective Endocarditis. AB - We report a case of aortic prosthetic valve endocarditis presenting with subaortic stenosis without perivalvular leakage and vegetations in the left ventricular outflow and right atrium, the latter being attached to the atrioventricular septum. Intraoperatively, an abscess that had formed on the aortic annulus and perforated to the right atrium was unexpectedly found, the fistula being occluded by vegetations. Even when no left-to-right shunts are detected by imaging, vegetations adjacent to the atrioventricular septum may conceal a left ventricle-right atrium fistula, resulting in prosthetic valve endocarditis presenting clinically as subaortic stenosis without perivalvular leakage. PMID- 27549557 TI - Splenectomy and Valve Replacement in Patients With Infective Endocarditis and Splenic Abscesses. AB - In patients with infective endocarditis (IE), splenic involvement is a rare but well-known adverse event. The treatment of patients with IE and splenic abscesses is still challenging and controversial. We report 3 patients with IE and splenic abscesses who underwent successful valve replacement and splenectomy. Our experience confirms that in such a patient, a valve operation combined with splenectomy can be performed with excellent results during the same hospitalization. The timing of splenectomy and the type of surgical approach should be based mainly on the stability of a patient's hemodynamic condition. PMID- 27549558 TI - Bilateral Intralobar Pulmonary Sequestration With a Bridging Isthmus in a Young Adult. PMID- 27549559 TI - Aortic Dissection Type B Causing Esophageal Perforation. PMID- 27549560 TI - Contrast-Enhanced Transthoracic Aortic Ultrasonography for Endoleak Detection After Thoracic Endovascular Aortic Repair. PMID- 27549561 TI - Gigantic Saphenous Vein Graft Aneurysm Presenting as Pulsatile Anterior Chest Wall Mass. PMID- 27549562 TI - Easier Uniportal VATS Lobectomy Using a Clamp With a String and a U-shaped Direction Converter for Lung Traction. AB - Although uniportal video-assisted thoracoscopic surgery (UVATS) is associated with decreased pain and chest wall paresthesia, as well as better cosmesis, it has not been widely accepted by thoracic surgeons. This lack of acceptance is largely because instrument collisions are difficult to avoid when many instruments are crowded into a single incision. We designed a set of instruments, including a clamp with a string and a U-shaped direction converter for lung traction, to provide better exposure during UVATS for lobectomy without the need for an endograsper. By retracting from different directions and applying appropriate force on the lung hilum to keep the vessels and bronchus separated, we were able to reduce collisions among instruments and make UVATS for lobectomy easier. PMID- 27549563 TI - Premeasured Chordal Loops for Mitral Valve Repair. AB - Premeasured expanded polytetrafluoroethylene chordal loops with integrated sutures for attachment to the papillary muscle and leaflet edges facilitate correction of mitral valve prolapse. Configured as a group of 3 loops (length range 12 to 24 mm), the loops are attached to a pledget that is passed through the papillary muscle and tied. Each of the loops has 2 sutures with attached needles; these needles are passed through the free edge of the leaflet and then the sutures are tied to each other, securing the chordal loop to the leaflet. PMID- 27549564 TI - Use of the Rigid Table Mount System During Transcatheter Aortic Valve Replacement With the Direct Aortic Approach. AB - Although the direct aortic approach is one option in performing transcatheter aortic valve replacement, it is essential to keep a sheath manually in the same position during the procedure. Holding the sheath by hand is not ideal because of the relatively high dose of radiation to the person who holds the sheath. We here describe a unique way to keep the sheath firm with a table mount system. PMID- 27549565 TI - Novel Annular and Subvalvular Enlargement in Congenital Mitral Valve Replacement. AB - Reparative procedures are not always feasible in congenitally abnormal mitral valves. Mechanical prosthesis has been accepted as the choice for valve replacement in the pediatric population. This report describes a case of congenital mitral valve disease requiring mitral valve replacement. The infant's mitral valve annulus was not amenable to placement of the smallest available mechanical prosthesis. The approach used here for annular and subvalvular enlargement facilitated implantation of a larger prosthesis for congenital mitral valve replacement. Five-year outcomes in a single patient may indicate broader applicability and avoidance of patient-prosthesis mismatch. PMID- 27549566 TI - Robots drive the German radical prostatectomy market: a total population analysis from 2006 to 2013. AB - BACKGROUND: To assess trends in the distribution of patients for radical prostatectomy in Germany from 2006 to 2013 and the impact of robotic surgery on annual caseloads. We hypothesized that the advent of robotics and the establishment of certified prostate cancer centers caused centralization in the German radical prostatectomy market. METHODS: Using remote data processing we analyzed the nationwide German billing data from 2006 to 2013. We supplemented this database with additional hospital characteristics like the prostate cancer center certification status. Inclusion criteria were a prostate cancer diagnosis combined with radical prostatectomy. Hospitals with certification or a surgical robot in 2009 were defined as 'early' group. Linear covariant-analytic models were applied to describe trends over time. RESULTS: Annual radical prostatectomy numbers declined from 28 374 (2006) to 21 850 (2013). High-volume hospitals (?100 cases) decreased from 87 (22.0%) in 2006 to 43 (10.4%) in 2013. Low-volume hospitals (<50 cases) increased from 193 (48.7%) to 280 (67.4%). Mean radical prostatectomy caseloads of hospitals with early vs without certification declined from 155 to 130 vs 77 to 39 (P=0.021 for trend comparison). Early robotic hospitals maintained their volume >200 cases per year contrary to the overall trend (P<0.001 for trend comparison). A multivariate model for caseload numbers of 2013 indicated a robotic system to be the most important factor for higher caseloads (multiplication factor 7.3; 95% confidence interval: 6.6-8.0). A prostate cancer center certification (multiplication factor 1.6; 95% confidence interval: 1.50-1.59) had a much smaller impact. CONCLUSIONS: We found decentralization of radical prostatectomy in Germany. The driving force for this development might consist in the overall decline of radical prostatectomy numbers. The most important factor for achieving higher caseloads was the presence of a robotic system. In order to optimize outcomes of radical prostatectomy additional health policy measures might be necessary. PMID- 27549567 TI - Inhibitory mechanism of morin on alpha-glucosidase and its anti-glycation properties. AB - It is important to investigate the inhibition of alpha-glucosidase due to its correlation with type 2 diabetes. Morin was found to exert significant inhibition activity on alpha-glucosidase in a reversible mixed-type manner with an IC50 value of (4.48 +/- 0.04) MUM. Analyses of fluorescence and circular dichroism spectra indicated that the formation of the morin-alpha-glucosidase complex was driven mainly by hydrophobic forces and hydrogen bonding, and caused the conformational changes of alpha-glucosidase. The phase diagrams of fluorescence showed that the conformational change process was monophasic without intermediates. Molecular docking indicated that morin mainly interacted with amino acid residues located close to the active site of alpha-glucosidase, which may move to cover the active pocket to reduce the binding of the substrate and then inhibit the catalytic activity. Morin was also found to exhibit inhibition in the generation of advanced glycation end products which was related to the long term complications of diabetes. PMID- 27549568 TI - Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions. AB - Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis. This study aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). Microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of alpha-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, we identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, alpha SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice. In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN. PMID- 27549569 TI - Global threats from invasive alien species in the twenty-first century and national response capacities. AB - Invasive alien species (IAS) threaten human livelihoods and biodiversity globally. Increasing globalization facilitates IAS arrival, and environmental changes, including climate change, facilitate IAS establishment. Here we provide the first global, spatial analysis of the terrestrial threat from IAS in light of twenty-first century globalization and environmental change, and evaluate national capacities to prevent and manage species invasions. We find that one sixth of the global land surface is highly vulnerable to invasion, including substantial areas in developing economies and biodiversity hotspots. The dominant invasion vectors differ between high-income countries (imports, particularly of plants and pets) and low-income countries (air travel). Uniting data on the causes of introduction and establishment can improve early-warning and eradication schemes. Most countries have limited capacity to act against invasions. In particular, we reveal a clear need for proactive invasion strategies in areas with high poverty levels, high biodiversity and low historical levels of invasion. PMID- 27549570 TI - Effectiveness of a community-based nutrition programme to improve child growth in rural Ethiopia: a cluster randomized trial. AB - Few trials have shown that promoting complementary feeding among young children is effective in improving child linear growth in resource-challenged settings. We designed a community-based participatory nutrition promotion (CPNP) programme adapting a Positive Deviance/Hearth approach that engaged mothers in 2-week nutrition sessions using the principles of 'learning by doing' around child feeding. We aimed to test the effectiveness of the CPNP for improving child growth in rural Ethiopia. A cluster randomized trial was implemented by adding the CPNP to the existing government nutrition programmes (six clusters) vs. government programmes only (six clusters). A total of 1790 children aged 6 to 12 months (876 in the intervention and 914 in the control areas) were enrolled and assessed on anthropometry every 3 months for a year. Multi-level mixed-effect regression analysis of longitudinal outcome data (n = 1475) examined the programme impact on growth, adjusting for clustering and enrollment characteristics. Compared with children 6 to 24 months of age in the control area, those in the intervention area had a greater increase in z scores for length-for-age [difference (diff): 0.021 z score/month, 95% CI: 0.008, 0.034] and weight-for-length (diff: 0.042 z score/month, 95% CI: 0.024, 0.059). At the end of the 12-month follow-up, children in the intervention area showed an 8.1% (P = 0.02) and 6.3% (P = 0.046) lower prevalence of stunting and underweight, respectively, after controlling for differences in the prevalence at enrollment, compared with the control group. A novel CPNP programme was effective in improving child growth and reducing undernutrition in this setting. (c) 2016 John Wiley & Sons Ltd. PMID- 27549571 TI - Two-State Reactivity Mechanism of Benzene C-C Activation by Trinuclear Titanium Hydride. AB - The cleavage of inert C-C bonds is a central challenge in modern chemistry. Multinuclear transition metal complexes would be a desirable alternative because of the synergetic effect of multiple metal centers. In this work, carbon-carbon bond cleavage and rearrangement of benzene by a trinuclear titanium hydride were investigated using density functional theory. The reaction occurs via a novel "two-state reactivity" mechanism. The important elementary steps consist of hydride transfer, benzene coordination, dehydrogenation, oxidative addition, hydride-proton exchange, and reductive elimination. Most importantly, the ground state potential energy surface switches from nearly degenerate triplet and antiferromagnetic singlet states to a closed-shell singlet state in the dearomatization of benzene, which effectively decreases the activation barrier. Furthermore, the roles of the transition metal centers and hydrides were clarified. PMID- 27549572 TI - Supporting Women Planning a Vaginal Breech Birth: An International Survey. AB - OBJECTIVE: The aim of this study was to explore the experiences of women who planned a vaginal breech birth. METHOD: An online survey was developed consisting of questions regarding women's experiences surrounding planned vaginal breech birth. The survey was distributed between April 2014 and January 2015 to closed membership Facebook groups that had a consumer focus on vaginal breech birth. RESULTS: In total, 204 unique responses to the survey were obtained from women who had sought the option of a vaginal breech birth in a previous pregnancy. Most women (80.8%) stated that they were happy with the birth choices they made, and a significant proportion (89.4%) would attempt a vaginal breech birth in subsequent pregnancies. Less than half of women were formally referred to a clinician skilled in vaginal breech birth when their baby was diagnosed breech (41.8%), while the remainder sourced a clinician themselves. Half of the women felt supported by their care provider (56.7%) and less than half (42.3%) felt supported by family and friends. CONCLUSION: The women who responded to this international survey sought the option of a vaginal breech birth, were subsequently happy with this decision, and would attempt a vaginal breech birth in their next pregnancy. Access to vaginal breech birth is important for some women; however, this choice may be challenging to achieve. Consistent information and support from clinicians is important to assist decision-making. PMID- 27549573 TI - Introduction of New South Wales adult subcutaneous insulin-prescribing chart in a tertiary hospital: its impact on inpatient glycaemic control. AB - BACKGROUND: Erratic blood glucose levels (BGL) are commonly observed amongst patients with diabetes mellitus during hospital admission. Patients on insulin therapy often do not have their doses titrated adequately by their team doctors during admission, and insulin is well known to be a high-risk medication prone to administration error. AIM: To assess the impact of a state-wide adult subcutaneous insulin-prescribing chart (ASCIPC) on glycaemic control and insulin prescribing pattern in a tertiary hospital. METHODS: An audit on the clinical records of inpatients who were on subcutaneous insulin therapy in the first week of July 2014 (prior to ASCIPC, n = 56) and in the first week of July 2015 (10 months after introducing ASCIPC, n = 62) was conducted at Liverpool Hospital. RESULTS: Following the introduction of ASCIPC, fewer BGL readings were missed (9.1 vs 11.6%, P = 0.032), and medical officers were more likely to adjust insulin dosage (71.0 vs 42.6%, P = 0.002) when compared to baseline. Glycaemic control improved, with lower mean BGL (9.4 +/- 2.0 vs 10.4 +/- 2.6 mmol/L, P = 0.021) and a greater proportion of BGL within the normal range of 5-10 mmol/L (56.2 vs 47.7%, P = 0.041). Omission of insulin doses after ASCIPC remained common, with over 40% of patients having at least one dose of insulin omitted during the audit week. CONCLUSION: Our study showed that the introduction of ASCIPC had positive impacts on glycaemic management for patients on subcutaneous insulin therapy during admission. More work is required to reduce the rate of insulin omission and to improve further glycaemic control for inpatients. PMID- 27549574 TI - Fitting miniscleral contact lenses in Korean patients with keratoconus. AB - BACKGROUND: The aim was to evaluate the clinical results of fitting MSD miniscleral contact lenses (MSD; Happy Vision Corp, Anyang, Korea) in Korean patients with keratoconus. METHODS: This report presents a retrospective case review of 38 keratoconic patients fitted with MSD lenses. Visual acuity, comfort, mean wear time, final lens parameters, relationships between sagittal depth and topographic indices, success rate with the first lens ordered and adverse events were documented. RESULTS: The mean logMAR visual acuity was improved from 0.85 +/ 0.78 with glasses and 0.28 +/- 0.29 with corneal rigid gas-permeable lenses to 0.10 +/- 0.11 with miniscleral contact lenses. Ninety-seven per cent of patients found the miniscleral contact lenses to be comfortable and the mean daily wear time was 10.1 +/- 2.3 hours. The mean sagittal depth was 4.70 +/- 0.35 mm and there was no correlation between sagittal depth and topographic indices. An average of 3.4 trial lenses was needed to decide the ordered lens and 1.3 ordered lenses to achieve the optimal fitting. One patient discontinued the wear of the lenses after three months due to discomfort. CONCLUSION: The use of MSD miniscleral contact lenses is a good alternative for patients with keratoconus and for those who failed to respond to other types of lens rehabilitation that results in both successful visual outcome and comfort. PMID- 27549575 TI - Morphological and molecular identification of marine copepod Dioithona rigida Giesbrecht, 1896 (Crustacea:Cyclopoida) based on mitochondrial COI gene sequences, from Lakshadweep sea, India. AB - Morphological identification of the marine cyclopoid copepod Dioithona rigida in combination with sequencing a 645 bp fragment of mitochondrial cytochrome oxidase c subunit I (mtCOI) gene, collected from offshore waters of Kavarathi Island, Lakshadweep Sea, is presented in this study. Kiefer in 1935 classified Dioithona as a separate genus from Oithona. The main distinguishing characters observed in the collected samples, such as the presence of well-developed P5 with 2 setae, 5 segmented urosome, 12 segmented antennule, compact dagger-like setae on the inner margin of proximal segment of exopod ramus in P1-P4 and engorged portion of P1 bearing a spine, confirmed their morphology to D. rigida. A comparison of setal formulae of the exopod and endopod of D. rigida with those recorded previously by various authors are also presented here. Maximum likelihood Tree analysis exhibited the clustering of D. rigida sequences into a single clade (accession numbers KP972540.1-KR528588.1), which in contrast was 37-42% divergent from other Oithona species. Further intra-specific divergence values of 0-2% also confirmed the genetic identity of D. rigida species. Paracyclopina nana was selected as an out group displayed a diverged array. The present results distinctly differentiated D. rigida from other Oithona species. PMID- 27549576 TI - Not All Pericytes Are Born Equal: Pericytes from Human Adult Tissues Present Different Differentiation Properties. AB - Pericytes (PCs) have been recognized for a long time only as structural cells of the blood vessels. The identification of tight contacts with endothelial cells and the ability to interact with surrounding cells through paracrine signaling revealed additional functions of PCs in maintaining the homeostasis of the perivascular environment. PCs got the front page, in the late 1990s, after the identification and characterization of a new embryonic cell population, the mesoangioblasts, from which PCs present in the adult organism are thought to derive. From these studies, it was clear that PCs were also endowed with multipotent mesodermal abilities. Furthermore, their ability to cross the vascular wall and to reconstitute skeletal muscle tissue after systemic injection opened the way to a number of studies aimed to develop therapeutic protocols for a cell therapy of muscular dystrophy. This has resulted in a major effort to characterize pericytic cell populations from skeletal muscle and other adult tissues. Additional studies also addressed their relationship with other cells of the perivascular compartment and with mesenchymal stem cells. These data have provided initial evidence that PCs from different adult tissues might be endowed with distinctive differentiation abilities. This would suggest that the multipotent mesenchymal ability of PCs might be restrained within different tissues, likely depending on the specific cell renewal and repair requirements of each tissue. This review presents current knowledge on human PCs and highlights recent data on the differentiation properties of PCs isolated from different adult tissues. PMID- 27549578 TI - Probing and evaluating anion-pi interaction in meso-dinitrophenyl functionalized calix[4]pyrrole isomers. AB - We investigate anion-pi binding modes in a cis-isomer of 3,5-dinitrophenyl substituted calix[4]pyrrole with various anions via X-ray crystallographic analyses and compare its binding affinities with those of the corresponding trans isomer. Sandwich-type anion-pi interactions prove to not only enhancing anion binding abilities but also altering the anion-binding selectivity of the calix[4]pyrrole framework. PMID- 27549577 TI - Leptospiral renal colonization status in asymptomatic rural population of Tiruchirapalli district, Tamilnadu, India. AB - Humans are known to excrete leptospires in their urine after recovery from illness and there are reports showing development of asymptomatic leptospiruria in settings of high disease transmission. In this regard, we sought to evaluate the asymptomatic renal carriage status of humans in the highly endemic region of Tiruchirapalli district, Tamilnadu, India. A total of 245 asymptomatic participants were included. Urine and blood samples were collected and the extent of leptospiral infection was characterized by MAT, qPCR, 16S rRNA, and dot blot assay. The qPCR screening with urine DNA identified 129 (52.7%) positive samples further confirmed by nested PCR. The dot blot assay marked 30.2% (74/245) as true positives. The phylogenetic analysis showed the sequences to cluster with pathogenic Leptospira spp. Serological results showed 50 people with urine positivity to be negative for MAT and can probably be classified as 'asymptomatic individuals.' In conclusion, it can be speculated that in endemic regions there is a greater possibility of humans as maintenance host rather than incidental hosts. PMID- 27549579 TI - Recurrence rate and subjective symptoms after standardized (Hamburg protocol) phototherapeutic keratectomy on recurrent corneal erosions. AB - PURPOSE: To evaluate the objective and subjective outcome after phototherapeutic keratectomy (PTK) on recurrent corneal erosions (Hamburg protocol). METHODS: For the standardized PTK according to Hamburg protocol a manual abrasio corneae performed with 20 % alcohol is followed by an excimer ablation depth of >=15 MUm (group1 15 MUm; group 2 > 15 MUm ablation depth) and 7 mm optical zone. All patients (N = 48) were invited for follow-up examinations and the evaluation of changes concerning subjective symptoms. RESULTS: A significantly reduced subjective impairment of night vision, significantly less pain and less foreign body sensations (for all p < 0.05) were noted in 48 patients that met the inclusion criteria (26 women, 22 men). In the follow-up period an improvement of corrected distance visual acuities (cdva) from 0.80 to 1.08 (group 1) and from 0.58 to 0.99 (group 2) was demonstrated. CONCLUSION: PTK (Hamburg Schema) is a safe and effective procedure to reduce subjective symptoms and improve discomfort in recurrent corneal erosion. PMID- 27549580 TI - Concomitant 11p15.4-p15.5 duplication and terminal 22q13.33 deletion in a patient with features of Beckwith-Wiedemann syndrome. PMID- 27549581 TI - Impact of electronic medication reconciliation interventions on medication discrepancies at hospital transitions: a systematic review and meta-analysis. AB - BACKGROUND: Medication reconciliation has been identified as an important intervention to minimize the incidence of unintentional medication discrepancies at transitions in care. However, there is a lack of evidence for the impact of information technology on the rate and incidence of medication discrepancies identified during care transitions. This systematic review was thus, aimed to evaluate the impact of electronic medication reconciliation interventions on the occurrence of medication discrepancies at hospital transitions. METHODS: Systematic literature searches were performed in MEDLINE, PubMed, CINHAL, and EMBASE from inception to November, 2015. We included published studies in English that evaluated the effect of information technology on the incidence and rate of medication discrepancies compared with usual care. Cochrane's tools were used for assessment of the quality of included studies. We performed meta-analyses using random-effects models. RESULTS: Ten studies met our inclusion criteria; of which only one was a randomized controlled trial. Interventions were carried out at various hospital transitions (admission, 5; discharge, 2 and multiple transitions, 3 studies). Meta-analysis showed a significant reduction of 45 % in the proportion of medications with unintentional discrepancies after the use of electronic medication reconciliation (RR 0.55; 95 % CI 0.51 to 0.58). However, there was no significant reduction in either the proportion of patients with medication discrepancies or the mean number of discrepancies per patient. Drug omissions were the most common types of unintended discrepancies, and with an electronic tool a significant but heterogeneously distributed reduction of omission errors over the total number of medications reconciled have been observed (RR 0.20; 95 % CI 0.06 to 0.66). The clinical impact of unintended discrepancies was evaluated in five studies, and there was no potentially fatal error identified and most errors were minor in severity. CONCLUSION: Medication reconciliation supported by an electronic tool was able to minimize the incidence of medications with unintended discrepancy, mainly drug omissions. But, this did not consistently reduce other process outcomes, although there was a lack of rigorous design to conform these results. PMID- 27549582 TI - Black tea theaflavins attenuate Porphyromonas gingivalis virulence properties, modulate gingival keratinocyte tight junction integrity and exert anti inflammatory activity. AB - BACKGROUND AND OBJECTIVE: Over the last 10 years, bioactive plant food compounds have received considerable attention in regard to their beneficial effects against periodontal disease. In this study, we investigated the effects of black tea theaflavins (TFs) on the virulence properties of Porphyromonas gingivalis and gingival keratinocyte tight junction integrity. In addition, the effects of black tea TFs on the nuclear factor-kappaB (NF-kappaB) signaling pathway and proinflammatory cytokine/matrix metalloproteinase (MMP) secretion by monocytes/macrophages were assessed. MATERIAL AND METHODS: Virulence factor gene expression in P. gingivalis was investigated by quantitative real-time PCR. A fluorescence assay was used to determine P. gingivalis adherence to, and invasion of, a gingival keratinocyte monolayer. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. Proinflammatory cytokine and MMP secretion by P. gingivalis stimulated macrophages was quantified by ELISA. The U937-3xkappaB-LUC monocyte cell line transfected with a luciferase reporter gene was used to monitor NF kappaB activation. Gelatin degradation was monitored using a fluorogenic assay. RESULTS: Black tea TFs dose-dependently inhibited the expression of genes encoding the major virulence factors of P. gingivalis and attenuated its adherence to gingival keratinocytes. A treatment of gingival keratinocytes with black tea TFs significantly enhanced tight junction integrity and prevented P. gingivalis-mediated tight junction damage as well as bacterial invasion. Black tea TFs reduced the secretion of interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, chemokine (C-X-C) ligand 8, MMP-3, MMP-8 and MMP-9 by P. gingivalis stimulated macrophages and attenuated the P. gingivalis-mediated activation of the NF-kappaB signaling pathway. Lastly, black tea TFs inhibited gelatin degradation by MMP-9. CONCLUSION: This study provides clear evidence that black tea TFs represent promising multifunctional therapeutic agents for prevention and treatment of periodontal disease. PMID- 27549583 TI - Thin-layer voltammetry of soluble species on screen-printed electrodes: proof of concept. AB - Thin-layer diffusion conditions were accomplished on screen-printed electrodes by placing a controlled-weight onto the cast solution and allowing for its natural spreading. The restricted diffusive conditions were assessed by cyclic voltammetry at low voltage scan rates and electrochemical impedance spectroscopy. The relationship between the weight exerted over the drop and the thin-layer thickness achieved was determined, in such a way that the simple experimental set up designed for this work could be developed into a commercial device with variable control of the thin-layer conditions. The experimental results obtained resemble those reported for the voltammetric features of electroactive soluble species employing electrodes modified with carbon nanotubes or graphene layers, suggesting that the attainment of the benefits reported for these nanomaterials could be done simply by forcing the solution to spread over the screen-printed electrodic system to form a thin layer solution. The advantages of thin-layer voltammetry in the kinetic characterization of quasi-reversible and irreversible processes are highlighted. PMID- 27549584 TI - Effects of Sodium Restriction on Activation of the Renin-Angiotensin-Aldosterone System and Immune Indices During HIV Infection. AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients demonstrate increased activation of the renin-angiotensin-aldosterone system (RAAS). We evaluated changes in immune markers with physiological RAAS activation. METHODS: Immune activation markers were assessed serially in 18 HIV-infected and 7 non-HIV infected subjects consuming an ad libitum diet followed by a standardized low sodium diet. RESULTS: Levels of CCL-2 (P = .0004) and soluble CD163 (P = .0001) significantly increased with sodium restriction and RAAS activation, compared with levels in individuals with ad libitum sodium intake, among chronically treated HIV-infected subjects (mean duration of ART [+/-SEM], 11 +/- 1 years), but not among non-HIV-infected subjects of similar age and sex. CONCLUSIONS: Dietary sodium restriction, which activates RAAS, uniquely stimulates critical indices of immune activation during HIV infection. CLINICAL TRIALS REGISTRATION: NCT01407237. PMID- 27549586 TI - Evaluation of RealStar Reverse Transcription-Polymerase Chain Reaction Kits for Filovirus Detection in the Laboratory and Field. AB - BACKGROUND: Diagnosis of Ebola virus (EBOV) disease (EVD) requires laboratory testing. METHODS: The RealStar Filovirus Screen reverse transcription-polymerase chain reaction (RT-PCR) kit and the derived RealStar Zaire Ebolavirus RT-PCR kit were validated using in vitro transcripts, supernatant of infected cell cultures, and clinical specimens from patients with EVD. RESULTS: The Filovirus Screen kit detected EBOV, Sudan virus, Tai Forest virus, Bundibugyo virus, Reston virus, and Marburg virus and differentiated between the genera Ebolavirus and Marburgvirus The amount of filovirus RNA that could be detected with a probability of 95% ranged from 11 to 67 RNA copies/reaction on a LightCycler 480 II. The Zaire Ebolavirus kit is based on the Filovirus Screen kit but was optimized for detection of EBOV. It has an improved signal-to-noise ratio at low EBOV RNA concentrations and is somewhat more sensitive than the Filovirus kit. Both kits show significantly lower analytical sensitivity on a SmartCycler II. Clinical evaluation revealed that the SmartCycler II, compared with other real-time PCR platforms, decreases the clinical sensitivity of the Filovirus Screen kit to diagnose EVD at an early stage. CONCLUSIONS: The Filovirus Screen kit detects all human-pathogenic filoviruses with good analytical sensitivity if performed on an appropriate real-time PCR platform. High analytical sensitivity is important for early diagnosis of EVD. PMID- 27549585 TI - Metalloproteinases and Brain Arterial Remodeling Among Individuals With and Those Without HIV Infection. AB - BACKGROUND: This study tests the hypothesis that increased elastolytic activity is associated differentially with dolichoectasia in individuals with and those without human immunodeficiency virus (HIV) infection. METHODS: Large arteries from 84 autopsied brains from HIV-positive individuals and 78 autopsied brains from HIV-negative individuals were stained for metalloproteinase 2 (MMP-2), MMP 3, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, CD68, and caspase 3. Average pixel intensity was automatically obtained and categorized as high, moderate, or low. Dolichoectasia was defined as a lumen to wall ratio >=95th percentile. RESULTS: High MMP-9 staining alone (P = .001) or coexistent with low TIMP-2 staining was associated with dolichoectasia only in HIV-negative individuals (P = <.001). In HIV-positive individuals, MMP-9 was associated with dolichoectasia only when coexpressed with caspase 3 (P = .01). Thinning of the media was associated with CD68 staining (P = <.001) in HIV-negative individuals, while caspase 3 was associated with a thinner media only in HIV-positive individuals (P = .01). Media thickness modified the association between lumen to wall ratio and MMP expression. CONCLUSIONS: A role for MMP/TIMP balance in dolichoectasia appears more prominent in HIV-negative individuals, while apoptosis, mediated by caspase 3, is the most important determinant of media thinning in HIV-infected individuals. Furthermore, apoptosis and media thickness appear to mediate the effects of MMP in the HIV-infected population. PMID- 27549587 TI - Cerebroplacental ratio in pregnancies complicated by gestational diabetes mellitus. AB - OBJECTIVE: To assess the relationship between the cerebroplacental ratio (CPR) and intrapartum and perinatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). METHODS: This was a retrospective cohort study of women with a non-anomalous singleton pregnancy diagnosed with GDM who delivered at Mater Mothers' Hospital between 2007 and 2015. CPR was measured in 1089 cases between 34 + 0 and 36 + 6 weeks' gestation. CPR values were compared between groups categorized according to GDM treatment (by diet, oral hypoglycemic agent (OHA) or insulin). The association between CPR and intrapartum and perinatal outcomes was evaluated. RESULTS: No difference in CPR was observed between treatment groups. Fetuses with CPR < 10th centile were significantly more likely to have adverse composite perinatal outcome (odds ratio (OR) = 2.93 (95% CI, 1.95 4.40)), preterm delivery and low birth weight than fetuses with CPR >= 10th centile (all P < 0.001). These associations were present regardless of the type of GDM treatment. Fetuses of women with insulin-controlled GDM had poorer neonatal outcomes than did fetuses of women treated with OHA or dietary control alone. The risk of adverse outcome was significantly increased in the insulin treated group (OR = 1.75 (95% CI, 1.34-2.28); P < 0.001), which also had higher rates of preterm delivery and higher birth weight. CONCLUSION: Regardless of the type of treatment, a low CPR is associated with poorer neonatal outcome in women with GDM. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27549588 TI - A systematic review of the prevalence of sedentary behavior during the after school period among children aged 5-18 years. AB - BACKGROUND: Independent of physical activity levels, youth sedentary behaviors (SB) have negative health outcomes. SB prevalence estimates during discretionary periods of the day (e.g., after-school), inform the need for targeted period specific interventions. This systematic review aimed to determine children's and adolescents' SB prevalence during the after-school period. METHODS: A computerized search was conducted in October 2015 (analysed November 2015). Inclusion criteria were: published in a peer-reviewed English journal; participants aged 5-18 years; measured overall after-school sedentary time (ST) objectively, and/or specific after-school SBs (e.g., TV viewing) objectively or subjectively; and provided the percentage of the after-school period spent in ST/SB or duration of behavior and period to calculate this. Where possible, findings were analyzed by location (e.g., after-school care/'other' locations). The PRISMA guidelines were followed. RESULTS: Twenty-nine studies were included: 24 included children (<=12 years), four assessed adolescents (>12 years) and one included both; 20 assessed ST and nine assessed SB. On average, children spent 41% and 51% of the after-school period in ST when at after-school care and other locations respectively. Adolescents spent 57% of the after-school period in ST. SBs that children and adolescents perform include: TV viewing (20% of the period), non-screen based SB (including homework; 20%), screen-based SB (including TV viewing; 18%), homework/academics (13%), motorised transport (12%), social SB (9%), and screen-based SB (excluding TV viewing; 6%). CONCLUSION: Children spent up to half of the after-school period in ST and this is higher among adolescents. A variety of screen- and non-screen based SBs are performed after school, providing key targets for interventions. TRIAL REGISTRATION: PROSPERO registration number CRD42015010437. PMID- 27549589 TI - Demographic and Cognitive Profile of Individuals Seeking a Diagnosis of Autism Spectrum Disorder in Adulthood. AB - Little is known about ageing with autism spectrum disorder (ASD). We examined the characteristics of adults referred to a specialist diagnostic centre for assessment of possible ASD, 100 of whom received an ASD diagnosis and 46 did not. Few demographic differences were noted between the groups. Comorbid psychiatric disorders were high in individuals with ASD (58 %) and non-ASD (59 %). Individuals who received an ASD diagnosis had higher self-rated severity of ASD traits than non-ASD individuals. Within the ASD group, older age was associated with higher ratings of ASD traits and better cognitive performance. One interpretation is that general cognitive ability and the development of coping strategies across the lifespan, do not necessarily reduce ASD traits but may mitigate their effects. PMID- 27549590 TI - Protocol of the "As du Coeur" study: a randomized controlled trial on physical activity maintenance in cardiovascular patients. AB - BACKGROUND: Although the benefits of supervised physical activity programs in cardiac rehabilitation have been well documented, the amount of physical activity often drops quickly after the end of the supervised period. This trial (registered as ISRCTN77313697 ) will evaluate the effectiveness of an experimental intervention based on habit formation theory applied to physical activity maintenance. METHODS/DESIGN: Cardiovascular patients (N = 56) will be individually randomized into two groups. Two supervised physical activity (SPA) sessions per week will be offered to the first group for 20 weeks. Progressively autonomous physical activity (PAPA) will be offered to the second group as follows: 10 weeks of the same supervised program as the SPA group followed by 10 more weeks in which one supervised session will be replaced by a strategy to build and sustain the habit of autonomous practice of physical activity. The primary outcome is the amount of physical activity measured by the International Physical Activity Questionnaire (IPAQ; Craig et al., Med Sci Sport Exercises 35(8):1381-95, 2003). To compensate for the limited capacity to recruit subjects, multiple IPAQ measurements will be made (at T0, T5, T7, T9 and T12 months after the start of the intervention) and analyzed using the mixed model approach. We will also assess changes in physical and physiological indicators, automaticity of the physical activity behavior, motivation and quality of life. Last, we will assess the cost-effectiveness for each type of program. DISCUSSION: If proven to be effective, the PAPA intervention, which requires fewer supervised sessions, should provide a cost-effective solution to the problem of physical activity maintenance in cardiac rehabilitation. PMID- 27549592 TI - Is the Reluctance for the Implantation of Right Kidneys Justified? PMID- 27549591 TI - Nicotine self-administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats. AB - Nicotine, a major psychoactive component of tobacco smoke, alters gamma aminobutyric acid (GABA) modulation of dopamine neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self-administer intravenous nicotine (0.03 mg/kg/infusion) for 21 days in 1-hour daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 minutes or 72 hours after the last session, immunofluorescence measurements for PNNs, PRV and c-Fos were conducted. In VTA, nicotine self-administration reduced the number of PRV+ cells surrounded by PNNs at 45 minutes, as well as reducing the intensity of PNNs, suggesting a remodeling of GABA interneurons in this region; the number of PRV+ cells surrounded by PNNs was also reduced at 72 hours. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC) but not in medial prefrontal cortex (prelimbic or infralimbic), 45 minutes after the last session; PNNs were not detected in nucleus accumbens (shell or core). The reduction of PNNs in VTA and OFC was unrelated to c-Fos + cells, as the percent of wisteria floribunda agglutinin + cells co-expressing c-Fos was decreased in OFC but not in VTA. Thus, nicotine self-administration remodeled PNNs surrounding GABA interneurons in VTA and its indirect connections to OFC, suggesting a new possible molecular target where nicotine-induced neuroplasticity takes place. PNN manipulations may prevent or reverse the different stages of tobacco addiction. PMID- 27549593 TI - Benefit to Perform Indocyanine Green Clearance Test: Reply. PMID- 27549594 TI - Metabolic Surgery for Diabetes Treatment: Sleeve Gastrectomy or Gastric Bypass? AB - BACKGROUND: Bariatric surgery has gained reputation for its metabolic effect and is increasingly being performed to treat type 2 diabetes mellitus (T2DM). However, there is still a gray area regarding the choice of surgical procedure according to patient characteristics due to inadequate evidences, so far. We aim to compare the efficacy of two most commonly performed bariatric/metabolic surgeries, sleeve gastrectomy (SG) and gastric bypass (GB) with regard to remission of T2DM after surgery. METHODS: Outcomes of 579 (349 female and 230 male) patients who had undergone SG (109) or GB (470) for the treatment of T2DM with 1-year follow-up were assessed. The remission of T2DM after SG or GB surgery was evaluated in matched groups using the ABCD scoring system. The ABCD score is composed of the age, BMI, C-peptide levels and duration of T2DM (years). RESULTS: The weight loss of the SG patient at 1 year after surgery was similar to the GB patients [26.3 (1.1) vs. 32.6 (1.2) %; p = 0.258]. The mean BMI decreased from 35.7 (7.2) to 28.3 (3.7) Kg/m2 in SG patients at 1 year after surgery and decreased from 36.9 (7.2) to 26.7 (4.5) Kg/m2 in the GB patients. The mean HbA1c decreased from 8.8 to 6.1 % of the SG group and from 8.6 to 5.9 % of the GB group. Sixty-one (56.0 %) patients of the SG group and 300 (63.8 %) of the GB group achieved complete remission of T2DM (HbA1c < 6.0 %) at 1 year after surgery without statistical difference. However, GB exhibited significantly better glycemic control than the SG surgery in groups stratified by different ABCD score. At 5 year after surgery, GB had a better remission of T2DM than SG (53.1 vs. 35.3 %; p = 0.055). CONCLUSIONS: In conclusion, although both SG and GB are effective metabolic surgery, GB carries a higher power on T2DM remission than SG. ABCD score is useful in T2DM patient classification and selection for different procedures. PMID- 27549596 TI - Suturing Global Surgery into Global Health. PMID- 27549595 TI - Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer. AB - BACKGROUND: While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC). METHODS: Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age. RESULTS: The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p <= 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 >= 50 who also had lymph node metastasis. CONCLUSIONS: Examining an "all comer" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship. PMID- 27549597 TI - A Majority of Admitted Patients With Ruptured Abdominal Aortic Aneurysm Undergo and Survive Corrective Treatment: A Population-Based Retrospective Cohort Study. AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is an asymptomatic, potentially lethal condition predominantly found in elderly. The mortality is 100 % if rupture occurs and left untreated, but even in treated patients the mortality is substantial. Female sex and treatment with open repair rather than endovascular aortic repair (EVAR) have been reported to negatively affect outcome. The objective was to describe the contemporary care and outcome of all treated and untreated patients with ruptured AAA (rAAA) admitted to hospital. METHOD: Population-based retrospective investigation, including all patients admitted to the emergency departments within Stockholm County diagnosed with rAAA 2009-2013. All identified patients' charts (n = 297) were analyzed; the study cohort includes 283 verified patients. RESULTS: Men were in majority [214 (76 %), 69 (24 %) women] and were younger than women (78 vs 82 years, p < 0.001). A majority of patients were treated (212/283, 75 %), a similar proportion of women and men. Untreated patients had a higher mean age (84 vs 77 years, p < 0.001). The proportion treated with EVAR was 27 %, and they were older than OR treated (79 vs 76 years, p = 0.043). Forty-seven percentage of patients admitted with rAAA survived 30 days, and 62 % of treated patients survived 30 days. The 30-day mortality for women and men was similar. CONCLUSIONS: Our results and other contemporary series show a shift toward a higher rate of treated patients with rAAA, and improving outcomes, similar for women and men. The increased use of EVAR contributes to this improvement in short-term outcome. High age influences the willingness to treat patients with rAAA. PMID- 27549598 TI - Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach. AB - BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (<=3; 3 10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma. PMID- 27549600 TI - Utility of antenatal clinical factors for prediction of postpartum outcomes in women with gestational diabetes mellitus (GDM). AB - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with life-long increased risk of type 2 diabetes: affected women are advised to undergo oral glucose tolerance testing (OGTT) at 6-12 weeks postpartum, then glucose screening every 1-3 years. AIMS: We investigated whether in women with GDM, antenatal clinical factors predicted postpartum abnormal glucose tolerance and compliance with screening. MATERIALS AND METHODS: In women with GDM delivering 2007 to mid 2009 in a single hospital, antenatal/obstetric data and glucose tests at 6-12 weeks postpartum and during 5.5 years post-pregnancy were retrospectively collected. Predictors of return for testing and abnormal glucose tolerance were identified using multivariate analysis. RESULTS: Of 165 women, 117 (70.9%) returned for 6-12 week postpartum OGTT: 23 (19.6%) were abnormal. Smoking and parity, independent of socioeconomic status, were associated with non-return for testing. Fasting glucose >=5.4 mmol/L on pregnancy OGTT predicted both non-return for testing and abnormal OGTT. During 5.5 years post-pregnancy, 148 (89.7%) women accessed glucose screening: nine (6.1%) developed diabetes, 33 (22.3%) had impaired fasting glucose / impaired glucose tolerance. Predictors of abnormal glucose tolerance were fasting glucose >=5.4 mmol/L and 2-h glucose >=9.3 mmol/L on pregnancy OGTT (~2.5-fold increased risk), and polycystic ovary syndrome (~3.4 fold increased risk). Risk score calculation, based on combined antenatal factors, did not improve predictions. CONCLUSIONS: Antenatal clinical factors were modestly predictive of return for testing and abnormal glucose tolerance post-pregnancy in women with GDM. Risk score calculations were ineffective in predicting outcomes: risk scores developed in other populations require validation. Ongoing glucose screening is indicated for all women with GDM. PMID- 27549601 TI - Identifying and Predicting Distinct Patterns of Implementation in a School-Wide Behavior Support Framework. AB - The purpose of this study was to examine the extent to which distinct patterns of fidelity of implementation emerged for 5331 schools over a 5-year course of implementing school-wide positive behavioral interventions and supports (SWPBIS). We used latent class analysis to classify schools based on their likelihood of implementing SWPBIS with fidelity each year, then assessed school and district predictors of classifications. A four-class solution fit the model well, with two patterns of sustained implementation (Sustainers and Slow Starters) and two patterns of practice abandonment (Late Abandoners and Rapid Abandoners). Significant predictors of group membership included grade levels served, enrollment, proportion of schools implementing SWPBIS in the district ("critical mass"), and size of the implementation cohort ("community of practice"). Elementary schools, larger schools, schools in districts with more schools already implementing SWPBIS, and those starting within a larger initial district cohort were more likely to be in the sustaining classes. Results are discussed in terms of understanding patterns of implementation in schools to enhance sustained implementation of school practices. PMID- 27549599 TI - Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations. AB - BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal pathway developed to overcome the deleterious effect of perioperative stress after major surgery. In colorectal surgery, ERAS pathways reduced perioperative morbidity, hospital stay and costs. Similar concept should be applied for liver surgery. This study presents the specific ERAS Society recommendations for liver surgery based on the best available evidence and on expert consensus. METHODS: A systematic review was performed on ERAS for liver surgery by searching EMBASE and Medline. Five independent reviewers selected relevant articles. Quality of randomized trials was assessed according to the Jadad score and CONSORT statement. The level of evidence for each item was determined using the GRADE system. The Delphi method was used to validate the final recommendations. RESULTS: A total of 157 full texts were screened. Thirty-seven articles were included in the systematic review, and 16 of the 23 standard ERAS items were studied specifically for liver surgery. Consensus was reached among experts after 3 rounds. Prophylactic nasogastric intubation and prophylactic abdominal drainage should be omitted. The use of postoperative oral laxatives and minimally invasive surgery results in a quicker bowel recovery and shorter hospital stay. Goal directed fluid therapy with maintenance of a low intraoperative central venous pressure induces faster recovery. Early oral intake and mobilization are recommended. There is no evidence to prefer epidural to other types of analgesia. CONCLUSIONS: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol. PMID- 27549602 TI - A Web-Based Intervention to Reduce Indoor Tanning Motivations in Adolescents: a Randomized Controlled Trial. AB - Youthful indoor tanning as few as ten sessions can increase the risk of melanoma by two to four times with each additional session adding another 2 % to the risk. Recent research estimates that indoor tanning can be linked to approximately 450,000 cases of skin cancer annually in the USA, Europe, and Australia. Despite these risks, indoor tanning remains popular with adolescents. This study tested the efficacy of a web-based skin cancer prevention intervention designed to reduce indoor tanning motivations in adolescent females. A nationally representative sample of 443 female teens was enrolled from an online panel into a two-arm, parallel group design, randomized controlled trial. Treatment participants received an appearance-focused intervention grounded in established health behavior change models. Controls viewed a teen alcohol prevention website. Outcome variables included willingness and intentions to indoor tan, willingness to sunless tan, and measures of indoor tanning attitudes and beliefs. The intervention decreased willingness and intentions to indoor tan and increased sunless tanning willingness relative to controls. We also examined indirect mechanisms of change through intervening variables (e.g., indoor tanning attitudes, norms, positive and negative expectancies) using the product of coefficient approach. The web-based intervention demonstrated efficacy in changing adolescent indoor tanning motivations and improving their orientation toward healthier alternatives. Results from the intervening variable analyses give guidance to future adolescent skin cancer prevention interventions. PMID- 27549603 TI - Methemoglobin measurements are underestimated by the Radical 7 co-oximeter: experience from a series of moderate to severe propanil poisonings. AB - INTRODUCTION: In Asia methemoglobinemia (MetHb) is commonly caused through self poisoning with the pesticide propranil. MetHb can cause hypoxia, coma and death, but usually responds to methylene blue. It is therefore vital to have accurate methods to measure blood MetHb to guide appropriate treatments. The gold standard to measure MetHb utilizes a spectrophotometer, but recent bedside tests have been developed e.g., pulse co-oximeter probe and blood color chart. METHODS: Nine propanil poisoned patients had data collected from hospitals in Sri Lanka during 2008. Several MetHb readings were taken from each patient from admission up to 50 hours using spectrophotometry (Unico UV-Vis model no. 2800), pulse co-oximetry (Radical-7, Masimo, CA), and color chart. RESULTS: The co-oximeter underestimated the MetHb percentage when compared with spectrophotometry and the color chart, especially when the average MetHb was greater than 20%. The color chart demonstrated acceptable accuracy compared with formal spectrophotometry with the majority of values showing no more than 10% difference. CONCLUSION: This small cohort highlights the potential for extreme inaccuracy of the Radical-7 co oximeter, especially with a MetHb greater than 20%. Pulse co-oximeters should be required to be validated for the complete range of MetHb prior to regulatory approval. PMID- 27549604 TI - Benzodiazepine Misuse in the Elderly: Risk Factors, Consequences, and Management. AB - Benzodiazepine (BZD) inappropriate use (i.e., misuse and overuse) is a worldwide public health problem. Despite current knowledge about increased sensitivity to side effects in the elderly, that should lead to more caution, only a third of BZD prescriptions in this age group are considered appropriate. The most frequent inadequate situations are excessive duration and/or dosage of a medical prescription or self-medication, especially in a context where it would be contraindicated, e.g., long-acting BZD in the elderly. Polypharmacy and comorbidities are major risk factors. Consequences of BZD inappropriate use are falls, delirium and other cognitive dysfunction, acute respiratory failure, car accidents, dependence, and withdrawal symptoms. An emerging concern is a potentially increased risk of dementia. Contrary to most clinicians' belief, discontinuation of chronic BZD use in elderly patients is feasible, with adequate psychotherapeutic or pharmacological strategies, and can lead to long-term abstinence. Brief cognitive therapy mostly relies on psychoeducation and motivational enhancement and is particularly useful in this context. Further research is needed, notably in three areas: (1) assessing the impact of public health programs to prevent BZD inappropriate use in the elderly, (2) developing alternative strategies to treat anxiety and insomnia in elderly patients, and (3) exploring the association between chronic BZD use and dementia. PMID- 27549606 TI - A reach-to-touch investigation on the nature of reading in the Stroop task. AB - In a Stroop task, participants can be presented with a color name printed in color and need to classify the print color while ignoring the word. The Stroop effect is typically calculated as the difference in mean response time (RT) between congruent (e.g., the word RED printed in red) and incongruent (GREEN in red) trials. Delta plots compare not just mean performance, but the entire RT distributions of congruent and incongruent conditions. However, both mean RT and delta plots have some limitations. Arm-reaching trajectories allow a more continuous measure for assessing the time course of the Stroop effect. We compared arm movements to congruent and incongruent stimuli in a standard Stroop task and a control task that encourages processing of each and every word. The Stroop effect emerged over time in the control task, but not in the standard Stroop, suggesting words may be processed differently in the two tasks. PMID- 27549607 TI - Factors Associated With Black Men's Preference for Health Information. AB - Black men are less likely to seek routine health care examinations or preventative care compared with their racial/ethnic and gender counterparts. Because of Black men's limited engagement with the health system, Black men's preference to receive health information is unclear. Guided by a revised version of the Andersen Healthcare Utilization Model, the aim of the study is to examine factors associated with Black men's preference for informal or formal health information. Findings from the study demonstrate that financial barriers to care (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43-0.98) and higher income (OR = 2.44, 95% CI = 1.49-4.00) were most predictive of using a formal source for health information. Furthermore, age (OR = 1.02, 95% CI = 1.01-1.03) and having a college education (OR = 0.44, 95% CI = 0.26-0.76) were associated with using a formal place for health information. Interestingly, health care discrimination was not associated with preferred source or place for health information. Results from the study suggest that predisposing and enabling factors are most salient to the use of formal sources of health information among Black men. PMID- 27549605 TI - Can Neuroimaging Provide Reliable Biomarkers for Obsessive-Compulsive Disorder? A Narrative Review. AB - In this integrative review, we discuss findings supporting the use neuroimaging biomarkers in the diagnosis and treatment of obsessive-compulsive disorder (OCD). To do so, we have selected the most recent studies that attempted to identify the underlying pathogenic process associated with OCD and whether they provide useful information to predict clinical features, natural history or treatment responses. Studies using functional magnetic resonance (fMRI), voxel-based morphometry (VBM), diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in OCD patients are generally supportive of an expanded version of the earlier cortico-striatal-thalamus-cortical (CSTC) model of OCD. Although it is still unclear whether this information will be incorporated into the daily clinical practice (due to current conceptual approaches to mental illness), statistical techniques, such as pattern recognition methods, appear promising in identifying OCD patients and predicting their outcomes. PMID- 27549608 TI - Comparison of Orthodontics-First and Surgery-First Approach in Positional Changes of the Condyle After Mandibular Setback Surgery Using Three-Dimensional Analysis. AB - PURPOSE: To examine and compare the 3-dimensional (3D) postoperative changes of the condylar position after mandibular setback surgery using the orthodontics first approach (OFA) and surgery-first approach (SFA). MATERIALS AND METHODS: This retrospective cohort study included patients who had undergone bilateral sagittal split ramus osteotomy for mandibular prognathism using OFA or SFA. Computed tomography images were obtained and analyzed preoperatively (T0), postoperatively (T1), and at the 6-month follow-up visit (T2). The bodily shift of the condylar center and rotational movement of the condylar head were measured using the 3D coordinate system between each time point and compared between the OFA and SFA groups. Repeated measures analysis of variance with a Bonferroni post hoc test was used to compare the time course changes of the condylar position for the 2 surgical-orthodontic approaches. RESULTS: A total of 55 patients (mean age 21.9 years; 31 males, 24 females) were evaluated. Of the 55 patients, 29 had undergone OFA and 26, SFA. In both groups, the condyle showed perioperative lateral and inferior displacement with inward rotation, followed by returning to its preoperative position during the 6 months postoperatively. No significant difference was found between the 2 groups in the time course change of the condylar position. CONCLUSIONS: Regardless of the timing of the operation (OFA vs SFA), the perioperative and postoperative changes of the condylar position after mandibular setback surgery are equivalent. PMID- 27549609 TI - NHS must do more to tackle white male dominance of leadership roles, Labour Party says. PMID- 27549610 TI - A selective fluorescent sensor for Zn(2+) based on aggregation-induced emission (AIE) activity and metal chelating ability of bis(2-pyridyl)diphenylethylene. AB - Polypyridyl ethylenes have been prepared as heterocyclic analogues of tetraphenylethylene. In addition to conventional AIE effects, a derivative possessing a 1,1-bis(2-pyridyl)ethylene fragment displays Zn(2+)-selective enhanced fluorescence in aqueous solution, in contrast to the behavior of isomeric bis(3- and 4-pyridyl)ethylenes. The Zn(2+)-sensing capability of this material is attributed to formation of chelated Zn(2+)-bis(pyridyl) complexes and is supported by the X-ray crystal structure of a bis(2-pyridyl)ethylene-Zn(OAc)2 complex. PMID- 27549611 TI - Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma. AB - Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro. PMID- 27549613 TI - Current evidence does not support the widespread use of collaborative care for PTSD, but it is limited by not evaluating context. PMID- 27549612 TI - Should tissue structure suppress or amplify selection to minimize cancer risk? AB - BACKGROUND: It has been frequently argued that tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical structure of tissues with high cell turnover, where a small number of tissue specific stem cells produces a large number of specialized progeny during multiple differentiation steps. Another well known mechanism is the spatial organization of stem cell populations and it is thought that this organization suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. RESULTS: We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organization of a cancer suppressing tissue architecture and should be taken into account in arguments for the evolution of such tissues. CONCLUSION: We show that for systems that are composed of few cells reflecting the typical organization of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special tissue structures that can suppress most types of non-neutral mutations simultaneously. REVIEWERS: This article was reviewed by Benjamin Allen, Andreas Deutsch and Ignacio Rodriguez-Brenes. For the full reviews, please go to the Reviewers' comments section. PMID- 27549614 TI - Annulation of o-Quinodimethanes through N-Heterocyclic Carbene Catalysis for the Synthesis of 1-Isochromanones. AB - The activation of 2-(bromomethyl)benzaldehydes using N-heterocyclic carbenes represents a novel approach to the generation of o-quinodimethane (o-QDM) intermediates. Coupling with ketones such as phenylglyoxylates, isatins, or trifluoromethyl ketones via [4 + 2] annulation gives access to functionalized 1 isochromanones. PMID- 27549616 TI - Restingomyces, a new sequestrate genus from the Brazilian Atlantic rainforest that is phylogenetically related to early-diverging taxa in Trappeaceae (Phallales). AB - Restingomyces reticulatus gen. et sp. nov. is a recently discovered false truffle species from Atlantic "restinga" rainforest in northeastern Brazil. Molecular and morphological characters separate this new sequestrate species from other described taxa in the order Phallales (Phallomycetidae, Basidiomycota). In our phylogenetic analysis based on nuc 28S rDNA and atp6, R. reticulatus forms a sister clade to Trappea darkeri and Phallobata alba, with the three taxa forming the earliest diverging lineage within Phallales. Morphological and molecular data warrant the recognition of the new genus and species, described here, and we also amend the taxonomic description for the family Trappeaceae. PMID- 27549617 TI - Phylogeny of Fomitopsis pinicola: a species complex. AB - Fungal species with a broad distribution may exhibit considerable genetic variation over their geographic ranges. Variation may develop among populations based on geographic isolation, lack of migration, and genetic drift, though this genetic variation may not always be evident when examining phenotypic characters. Fomitopsis pinicola is an abundant saprotrophic fungus found on decaying logs throughout temperate regions of the Northern Hemisphere. Phylogenetic studies have addressed the relationship of F. pinicola to other wood-rotting fungi, but pan-continental variation within F. pinicola has not been addressed using molecular data. While forms found growing on hardwood and softwood hosts exhibit variation in habit and appearance, it is unknown if these forms are genetically distinct. In this study, we generated DNA sequences of the nuc rDNA internal transcribed spacers (ITS), the TEF1 gene encoding translation elongation factor 1 alpha, and the RPB2 gene encoding the second largest subunit of RNA polymerase II for collections across all major geographic regions where this fungus occurs, with a primary focus on North America. We used Bayesian and maximum likelihood analyses and evaluated the gene trees within the species tree using coalescent methods to elucidate evolutionarily independent lineages. We find that F. pinicola sensu lato encompasses four well-supported, congruent clades: a European clade, southwestern US clade, and two sympatric northern North American clades. Each clade represents distinct species according to phylogenetic and population genetic species concepts. Morphological data currently available for F. pinicola do not delimit these species, and three of the species are not specific to either hardwood or softwood trees. Originally described from Europe, F. pinicola appears to be restricted to Eurasia. Based on DNA data obtained from an isotype, one well defined and widespread clade found only in North America represents the recently described Fomitopsis ochracea The remaining two North American clades represent previously undescribed species. PMID- 27549615 TI - Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. RESULTS: We performed a linear mixed-model (LMM) analysis using 16 variably affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. CONCLUSIONS: The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes. PMID- 27549618 TI - Two new Lactarius species from a subtropical cloud forest in eastern Mexico. AB - Two species of Lactarius from the subtropical montane cloud forest of central Veracruz are described as new. Both species are placed in subgenus Lactarius based on an accurate study of macro- and micromorphological features and supported by molecular phylogenetic analyses of a single nuc rDNA ITS1-5.8S-ITS2 (ITS), a concatenated ITS, D1, and D2 domains of nuc 28S rDNA (28S), and part of the second largest subunit of the RNA polymerase II (rpb2) (6-7 region) sequence datasets. In the phylogenetic reconstruction presented, the two species appear nested in two clearly distinct, well supported clades that reveal their phylogenetic position among members of subgenus Lactarius (= subg. Piperites s. auct.), a complex group of which a worldwide phylogeny requires further study. According to field observations, both taxa are possible ectomycorrhizal associates of Quercus spp. and one of Fagus grandifolia var. mexicana Taxonomic descriptions based on the study of specimens gathered during fieldwork from 2012 to 2014 are presented. Descriptions are accompanied with illustrations of macro and micromorphological characters and a discussion of related species is provided. PMID- 27549619 TI - Curvularia malina sp. nov. incites a new disease of warm-season turfgrasses in the southeastern United States. AB - A novel species of Curvularia was identified as a foliar pathogen of Cynodon dactylon (bermudagrass) and Zoysia matrella (zoysiagrass), two important warm season turfgrasses in the southeastern United States. Field symptoms were conspicuous chocolate brown to black spots in turf of both species on golf course putting greens and fairways. Leaves of plants within these spots exhibited prominent, black eyespot lesions from which a darkly pigmented fungus was consistently isolated. The fungus produced gray- to black-olivaceous mycelium within 10 d on potato dextrose agar at 25 C but never produced conidia despite numerous attempts to induce them. Field symptoms were reproduced in inoculated plants of both grasses, and re-isolation of the pathogen from symptomatic tissues confirmed its pathogenicity in fulfillment of Koch's postulates. A phylogenetic analysis was performed using sequence markers of internal nuclear ribosomal transcribed spacer region (ITS), glyceralde-hyde-3-phosphate dehydrogenase (GPD1) and translation elongation factor 1-alpha (TEF 1). The concatenated phylogenetic tree showed strong support for a new species within Curvularia that is distinctly divergent from other Curvularia spp. Therefore, the darkly pigmented pathogen of warm-season turfgrasses is described and illustrated as a new species, Curvularia malina. PMID- 27549620 TI - Cortinarius subgenus Callistei in North America and Europe-type studies, diversity, and distribution of species. AB - Five species of Cortinarius subgenus Callistei, are recognized in Europe and North America. Cortinarius callisteus, C. infucatus, and C. neocallisteus sp. nov. have a broad distribution, extending from western North America to Europe. Cortinarius tofaceus is known from eastern North America and Europe, while C. callistei sp. is known only from one locality in Sweden. All five species are primarily associated with coniferous trees. Previously the species were included either in subgenus Leprocybe or subgenus Cortinarius, but recently they have been separated into subgenus Callistei based on molecular data. Type specimens of the names associated with this subgenus were studied and a neotype proposed for C. tofaceus and an epitype for C. infucatus Barcodes for the species are deposited in RefSeq and UNITE. PMID- 27549621 TI - Multilocus phylogenetic reconstruction of the Clavariaceae (Agaricales) reveals polyphyly of agaricoid members. AB - The genus Camarophyllopsis contains species with lamellate (agaricoid) basidiomes in the family Clavariaceae (Agaricales), a group otherwise dominated by club-like (clavarioid) or branched (coralloid) forms. Previous studies have suggested that species classified in Camarophyllopsis occur in two independent lineages. We reconstructed a multilocus phylogeny of the Clavaria-Camarophyllopsis-Clavicorona clade in the Clavariaceae using RNA polymerase II second largest subunit (rpb2), nuclear ribosomal 28S, and nuclear ribosomal ITS1-5.8S-ITS2 regions data and detected three independent groups of agaricoid fungi, including the genera Camarophyllopsis, Hodophilus, and Lamelloclavaria gen. nov, which distinctly differ in their pileipellis structure. In all, nine major lineages within the Clavaria-Camarophyllopsis-Clavicorona clade were recovered: Clavaria sensu stricto, Camarophyllopsis sensu stricto, Hodophilus, the Clavaria pullei clade, the Clavaria fumosa clade, Lamelloclavaria gen. nov., the Clavaria atrofusca clade, Holocoryne (= Clavaria sect. Holocoryne), and Clavicorona Clavaria is paraphyletic and represented by five clades. Additional gene sampling is necessary to determine and confirm relatedness of these lineages before splitting Clavaria into additional genera. PMID- 27549622 TI - Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy in a patient with recurrent breast cancer: a case report. AB - BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare complication of advanced cancer, is histologically characterized by tumor embolisms and fibrocellular intimal proliferation of small pulmonary arteries and arterioles. PTTM usually has an extremely poor prognosis, and antemortem diagnosis is very difficult. CASE PRESENTATION: A 65-year-old woman with a 5-year history of clinical stage IIA (T2N0M0) invasive ductal carcinoma of the left breast was hospitalized for worsening shortness of breath, hemoptysis, and cough since 2 months. She had previously received neoadjuvant chemotherapy and left mastectomy. Because the cancer cells were positive for human epidermal growth factor receptor 2 (HER2), four cycles of trastuzumab had been administered as adjuvant chemotherapy. On admission, chest computed tomography (CT) showed peripheral consolidations in both the lower lobes and a mediastinal mass. Specimens obtained on video-assisted thoracoscopic surgical biopsy revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi, recanalization, and infarction in the left lower lobe, as well as metastasis to the mediastinal pleura. Immunohistochemical staining of the tumor cells revealed positivity for HER2, and a diagnosis of recurrent breast cancer with PTTM was made. Four cycles of trastuzumab resulted in rapid improvement of her symptoms and CT findings of peripheral consolidations and the mediastinal mass. CONCLUSION: An antemortem diagnosis of PTTM was made in a patient with HER2 positive recurrent breast cancer. Trastuzumab was effective for not only breast cancer but also PTTM. PMID- 27549623 TI - Receiver operating characteristics of impulse oscillometry parameters for predicting obstructive sleep apnea in preobese and obese snorers. AB - BACKGROUND: Inability to maintain upper-airway patency during sleep is a cause of obstructive sleep apnea (OSA) and its sequelae. The associated syndrome (OSAS) is common in obese populations, currently, nocturnal polysomnography is the gold standard for diagnosing this conditions, but the diagnostic procedures are expensive and time-consuming. Therefore, identification of new markers of OSAS would be useful. This study aims to examine the receiver operating characteristics of impulse oscillometry (IOS) parameters for the prediction of OSAS in preobese and obese snoring patients. METHODS: In total, 230 patients with normal spirometric values were included in this cross-sectional study. Full laboratory polysomnography was performed and IOS measurements were determined in sitting and supine positions to obtain respiratory impedance (Zrs), resistance (Rrs), and reactance (Xrs) parameters. The respiratory resistance at zero frequency (Rrs0) was extrapolated by linear regression analysis of Rrs versus low oscillatory-frequencies and its inverse, respiratory conductance (Grs), was calculated. RESULTS: In both the sitting and supine positions Rrs0, Zrs, and Rrs at five oscillatory-frequencies (Hz) and Grs, the reciprocal of Zrs5 (Gz), and Xrs at 5 Hz all had significant positive or negative correlations with OSAS severity as defined by the Respiratory disturbance index (RDI). The correlation coefficients between Rrs0, Zrs5, Rrs5, Grs, Gz, Xrs5 measured in the supine and RDI were 0.425, 0.395, 0.378, -0.425, -0.395, and -0.517, respectively (all p < 0.001). The receiver operating characteristics curves showed that Xrs at 5 Hz (reactance) in the supine position was the best for predicting OSAS with a sensitivity of 73 % and specificity of 84 % at the optimal cut-off point of -0.23 (kPa s L(-1)). The other parameters also showed acceptable discriminating power. A logistic-regression model based on respiratory function abnormalities revealed that reactance combined with patient sex and lung volume yielded a specificity of 83.3 % with a sensitivity of 76.8 % for indicating OSAS. CONCLUSION: Respiratory resistance and reactance measured by IOS are abnormal in preobese and obese OSAS patients, and these parameters are moderate to closely correlated with OSAS severity. IOS might be a useful screening tool for detecting OSAS in clinic based populations. PMID- 27549624 TI - Multiple cellular effects of leaf extracts from Parinari curatellifolia. AB - BACKGROUND: Parinari curatellifolia is a prominent plant in folk medicine in Sub Saharan Africa. The plant decoctions are used to treat various ailments, including the treatment of cancer, pneumonia, fever, microbial infections and anti-inflammation. The aims of the study were to investigate the effects of P. curatellifolia leaf extracts on cell inflammatory and proliferative activity. METHODS: Parinari curatellifolia fresh leaves were collected from Centenary in Mashonaland Central Province of Zimbabwe. Plant extracts were prepared using methanol, water, acetone and ethanol. Firstly, the effects of the extracts were determined on xanthine oxidase activity. Kinetic constants were determined for the extracts that showed inhibitory effects. Then the effects of Parinari curatellifolia water extract on LPS, menadione and hydrogen peroxide-activated nitric oxide production in RAW 264.7 cells was determined by quantifying the amount of nitrites formed. Finally, the effects of P. curatellifolia on the proliferation of Jurkat-T cells as well as its modulation of cisplatin-induced cell- cytotoxicity was investigated on a Jurkat human T-cell lymphoma cell line. RESULTS: There was significant XO inhibitory activity by the ethanol and methanol extracts at 15.6 MUg/ml and 3.9 MUg/ml respectively. The IC50 determination for allopurinol, ethanol extract and methanol extract were 0.43 MUg/ml, 1.38 MUg/ml and 2.19 MUg/ml respectively. The kinetic results showed that the ethanol and methanol extracts were allosteric inhibitors of XO. The water extract of P. curatellifolia inhibited NO production in RAW cells when LPS was used as an activator. P. curatellifolia and cisplatin showed dose-dependent cytotoxicity on Jurkat-T cells. Isolated DNA from the cells showed that there was DNA cleavage on cells exposed to P. curatellifolia indicating that apoptosis may be a mechanism by which P. curatellifolia exerts its cytotoxicity on Jurkat-T cells. CONCLUSIONS: These results scientifically support the use of P. curatellifolia leaf extracts in the management of pain, inflammatory and neoplastic conditions. P. curatellifolia thus has multiple biological effects, thus, validating its use in traditional medical uses. PMID- 27549625 TI - Fourth cranial nerve: surgical anatomy in the subtemporal transtentorial approach and in the pretemporal combined inter-intradural approach through the fronto temporo-orbito-zygomatic craniotomy. A cadaveric study. AB - Despite the recent progress in surgical technology in the last decades, the surgical treatment of skull base lesions still remains a challenge. The purpose of this study was to assess the anatomy of the tentorial and cavernous segment of the fourth cranial nerve as it appears in two different surgical approaches to the skull base: subtemporal transtentorial approach and pretemporal fronto-orbito zygomatic approach. Four human cadaveric fixed heads were used for the dissection. Using both sides of each cadaveric head, we made 16 dissections: 8 with subtemporal transtentorial technique and 8 with pretemporal fronto-orbito zygomatic approach. The first segment that extends from the initial point of contact of the fourth cranial nerve with the tentorium (point Q) to its point of entry into its dural channel (point D) presents an average length of 13.5 mm with an extremely wide range and varying between 3.20 and 9.3 mm. The segment 2, which extends from point D to the point of entry into the lateral wall of the cavernous sinus, presents a lesser interindividual variability (mean 10.4 mm, range 15.1 5.9 mm). A precise knowledge of the surgical anatomy of the fourth cranial nerve and its neurovascular relationships is essential to safely approach. The recognition of some anatomical landmarks allows to treat pathologies located in regions of difficult surgical access even when there is an important subversion of the anatomy. PMID- 27549626 TI - The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study. AB - BACKGROUND: The effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010 2011 seasonal inactivated influenza vaccination in children. METHODS: From October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination ( )/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+). RESULTS: Among the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9-18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1-7 year-old age group, there was no significant difference between the two groups. CONCLUSIONS: Previous H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older children. PMID- 27549627 TI - Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells. AB - BACKGROUND: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells. METHODS: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells. RESULTS: We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development. CONCLUSIONS: Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer. PMID- 27549629 TI - [Policy recommendations for the implementation of fall and fracture prevention in community-dwelling older persons]. AB - Several factors impede the implementation of effective strategies for fall and fracture prevention. The Centre of Expertise for Fall & Fracture prevention Flanders organized a symposium, "Implementation of fall en fracture prevention in older people", with the aim to elaborate on the facilitation of effective strategies for falls and fall-related injuries in community-dwelling older people in Flanders. This article summarizes the main bottlenecks for implementation and provides recommendations for optimizing dissemination and implementation. PMID- 27549628 TI - Extended N-terminal region of the essential phosphorelay signaling protein Ypd1 from Cryptococcus neoformans contributes to structural stability, phosphostability and binding of calcium ions. AB - Rapid response to external stimuli is crucial for survival and proliferation of microorganisms. Pathogenic fungi employ histidine-to-aspartate multistep phosphorelay systems to respond to environmental stress, progress through developmental stages and to produce virulence factors. Because these His-to-Asp phosphorelay systems are not found in humans, they are potential targets for the development of new antifungal therapies. Here we report the characterization of the histidine phosphotransfer (HPt) protein Ypd1 from the human fungal pathogen Cryptococcus neoformans Results from this study demonstrate that CnYpd1 indeed functions as a phosphorelay protein in vitro, and that H138 is confirmed as the site of phosphorylation. We found that CnYpd1 exhibits unique characteristics in comparison to other histidine phosphotransfer proteins, such as an extended N terminal amino acid sequence, which we find contributes to structural integrity, a longer phosphorylated life time and the ability to bind calcium ions. PMID- 27549630 TI - Acute hemichorea in a newly diagnosed type II diabetes patient: a diagnostic challenge in resource-limited setting: a case report. AB - BACKGROUND: Chorea is a rare complication of uncontrolled type II diabetes. We report for the first time in Tanzania a case of type II diabetes presenting with a hyperglycaemia-induced hemichorea. CASE PRESENTATION: A 58-year-old Tanzanian chagga by tribe with a body mass index of 28 kg/m(2) and newly diagnosed type II diabetes presented with polydipsia and involuntary movements of the right upper limb for 4 days. His plasma glucose was 549 mg/dl and glycated haemoglobin was 18.9 %. His movements were exaggerated by attempts to use his right hand. The rest of his neurological assessment was unremarkable. Other laboratory findings including calcium were within the normal range. A computed tomography scan of the brain was essentially normal except for age-related atrophy. There was no significant ketonuria on urine dipstick testing. We treated the patient's hyperglycaemia with intravenous insulin and the dystonia disappeared within 5 days. CONCLUSION: Hemichorea is among the rare complications of hyperglycaemia induced involuntary movements. Hyperglycaemia should be considered as a differential diagnosis for patients with type II diabetes mellitus presenting with hemichorea upon clinical assessment. PMID- 27549631 TI - Improved Sanitation Facilities are Associated with Higher Body Mass Index and Higher Hemoglobin Concentration Among Rural Cambodian Women in the First Trimester of Pregnancy. AB - Multiple factors contribute to undernutrition in Cambodian women. Our aim was to determine if type of household sanitation facility was associated with body mass index (BMI) and hemoglobin (Hb) concentration among pregnant women. Women (N = 544) from 75 villages in Kampong Chhnang Province had their height, weight, and Hb measured (HemoCue Hb 201+) in the first trimester. Sociodemographic and household characteristics were collected. Multivariable linear and logistic regression models were used for analyses. Approximately 40% (N = 221) of women reported primarily using an 'improved' sanitation facility (closed pit latrine) and ~60% (N = 323) used 'non-improved' facilities (open defecation). Mean +/- standard deviation (SD) BMI was higher among women with improved versus non improved facilities (19.9 +/- 3.0 kg/m2 versus 19.4 +/- 2.3 kg/m2; P = 0.01). Mean +/- SD Hb concentration was also higher among women with improved versus non improved facilities (118 +/- 12 g/L versus 114 +/- 14 g/L; P = 0.001). Anemia prevalence (Hb < 110 g/L) was higher among women with non-improved facilities (34% versus 25%; P = 0.04). An improved sanitation facility was a positive predictor of BMI (beta = 0.57 kg/m2; 95% confidence interval [CI] = 0.10, 1.04) and Hb concentration (beta = 2.94 g/L; 95% CI = 0.53, 5.35), adjusting for age, parity, household size, village, gestation week, source of drinking water, and iron folic acid supplementation. Poor sanitation was associated with lower BMI and Hb concentration among pregnant Cambodian women. This warrants multisectoral approaches involving the health, nutrition, water, and sanitation sectors to effectively improve maternal health in Cambodia. PMID- 27549632 TI - Exclusive Breastfeeding and Clinical Malaria Risk in 6-Month-Old Infants: A Cross Sectional Study from Kinshasa, Democratic Republic of the Congo. AB - The World Health Organization recommends exclusive breastfeeding (EBF) for the first 6 months of life. However, the effect of EBF on malaria risk remains unclear. In the present study, 137 EBF infants and 358 non-EBF infants from the Democratic Republic of the Congo were assessed for fever and malaria infections by polymerase chain reaction, at 6 months of age. EBF was associated with a reduced risk of clinical malaria (odds ratio = 0.13; 95% confidence interval = 0.00-0.80), suggesting a protective effect of EBF against malaria. PMID- 27549633 TI - Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil. AB - We evaluated the efficacy of chloroquine and primaquine on uncomplicated Plasmodium vivax malaria in Cruzeiro do Sul, Brazil, in 2014. Patients >= 5 years of age with either fever or history of fever, and laboratory-confirmed P. vivax monoinfection received chloroquine (total dose = 25 mg/kg) and primaquine (total dose = 3.5 mg/kg), and were followed up for 168 days (24 weeks). We used microsatellite genotyping to differentiate recurrent infections caused by heterologous parasites from those caused by homologous ones. No new P. vivax episode occurred by Day 28 among 119 enrolled patients, leading to Day 28, with adequate clinical and parasitological response (ACPR) of 100% (95% confidence interval [CI] = 96.7-100%). Twenty-eight P. vivax episodes occurred by Day 168, with uncorrected ACPR of 69.9% (95% CI = 59.5-79.0%). Fifteen of these episodes were caused by either homologous haplotypes or haplotypes that could not be determined. Excluding the 13 recurrent episodes caused by heterologous parasites, Day 168 microsatellite-corrected ACPR was estimated at 81.2% (95% CI = 71.0 89.1%). Chloroquine and primaquine remain efficacious to treat acute uncomplicated P. vivax infection, but moderate recurrence rates were observed within 24 weeks of follow-up. PMID- 27549634 TI - Successful Treatment of Cutaneous Leishmaniasis with Topical Paramomycin in a Child After Treatment Failure with Systemic Fluconazole. AB - It is challenging to find safe, nonscarring and noninvasive treatment of facial cutaneous leishmaniasis (CL) in children. Herein, we report a child with CL from a region endemic for Leishmania tropica, whose lesion persisted after treatment with oral fluconazole but responded to topical paromomycin. Paromomycin should be considered early for treatment of Old World CL and is a well-tolerated and effective mode of therapy for facial lesions. PMID- 27549636 TI - Development of Two FhSAP2 Recombinant-Based Assays for Immunodiagnosis of Human Chronic Fascioliasis. AB - In the United States, infection with Fasciola hepatica has been identified as an emerging disease, primarily in immigrants, refugees, and travelers. The laboratory test of choice for diagnosis of fascioliasis is detection of disease specific antibodies, most commonly uses excretory-secretory antigens for detection of IgG antibodies. Recently, recombinant proteins such as F. hepatica antigen (FhSAP2) have been used to detect IgG antibodies. The glutathione S transferase (GST)-FhSAP2 recombinant antigen was used to develop Western blot (WB) and fluorescent bead-based (Luminex) assays to detect F. hepatica total IgG and IgG4 antibodies. The sensitivity and specificity of GST-FhSAP2 total IgG and IgG4 WB were similar at 94% and 98%, respectively. For the IgG Luminex assay, the sensitivity and specificity were 94% and 97%, and for the IgG4, the values were 100% and 99%, respectively. In conclusion, the GST-FhSAP2 antigen performs well in several assay formats and can be used for clinical diagnosis. PMID- 27549635 TI - West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia. AB - In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites. PMID- 27549637 TI - Clinical Features of Human Immunodeficiency Virus-Infected Patients Presenting with Cholera in Port-au-Prince, Haiti. AB - Human immunodeficiency virus (HIV) infection has been postulated to alter the natural history of cholera, including increased susceptibility to infection, severity of illness, and chronic carriage of Vibrio cholerae Haiti has a generalized HIV epidemic with an adult HIV prevalence of 1.9% and recently suffered a cholera epidemic. We conducted a prospective study at the cholera treatment center (CTC) of GHESKIO in Haiti to characterize the coinfection. Adults admitted at the CTC for acute diarrhea were invited to participate in the study. Vital signs, frequency, and volume of stools and/or vomiting were monitored, and single-dose doxycycline was administered. After counseling, participants were screened for HIV by enzyme-linked immunosorbent assay and for cholera by culture. Of 729 adults admitted to the CTC, 99 (13.6%) had HIV infection, and 457 (63%) had culture-confirmed cholera. HIV prevalence was three times higher in patients without cholera (23%, 63/272) than in those with culture confirmed cholera (7.9%, 36/457). HIV prevalence in patients with culture confirmed cholera (7.9%) was four times higher than the adult prevalence in Port au-Prince (1.9%). Of the 36 HIV-infected patients with cholera, 25 (69%) had moderate/severe dehydration versus 302/421 (72%) in the HIV negative. Of 30 HIV infected patients with weekly stool cultures performed after discharge, 29 (97%) were negative at week 1. Of 50 HIV-negative patients with weekly stool cultures, 49 (98%) were negative at week 1. In countries with endemic HIV infection, clinicians should consider screening patients presenting with suspected cholera for HIV coinfection. PMID- 27549638 TI - Significance of Echogenic Snow Sign as an Ultrasonography Finding for Diagnosis of Urogenital Schistosomiasis. AB - Urogenital schistosomiasis (UGS) is one of the important neglected tropical diseases, which requires global elimination programs. It is primarily diagnosed by urine microscopy (UM), but its sensitivity is not satisfactory. Ultrasonography (US) is an alternative screening method of UGS. The present study investigated the diagnostic feasibility of new criteria including echogenic snow sign, innumerable scattered small echogenic foci floating in bladder lumen, for UGS in White Nile State, Republic of Sudan, 2013-2014. A total of 1,462 participants were screened by US or UM, and 948 by both. The 948 subjects were 1 80 years of age, 485 (51.2%) of them were boys or men, and 648 (68.4%) were less than 15 years of age. Eggs were detected from 133 (14.0%) by UM. The US findings of bladder wall thickening, polypoid mass, and ureter dilatation were regarded as positive for UGS following the World Health Organization (WHO) guidelines. Of the 948 subjects, 155 (16.4%) were positive for US by the WHO criteria. The echogenic snow sign was detected in 75 participants, and was most frequently observed in age group of 10-14. It was more commonly observed in UM-positive participants (35/133; 26.3%) than in UM-negative participants (40/815; 4.9%), and the difference was statistically significant with an odds ratio of 6.92 (4.20-11.41). When the echogenic snow was added to the WHO criteria, 42 participants were additionally revealed to have UGS-related morbidity, reaching a total of 198 (20.9%) participants. The echogenic snow sign can be suggested as a new finding to the criteria of US for UGS. PMID- 27549639 TI - Identification of Interictal Epileptic Networks from Dense-EEG. AB - Epilepsy is a network disease. The epileptic network usually involves spatially distributed brain regions. In this context, noninvasive M/EEG source connectivity is an emerging technique to identify functional brain networks at cortical level from noninvasive recordings. In this paper, we analyze the effect of the two key factors involved in EEG source connectivity processing: (i) the algorithm used in the solution of the EEG inverse problem and (ii) the method used in the estimation of the functional connectivity. We evaluate four inverse solutions algorithms (dSPM, wMNE, sLORETA and cMEM) and four connectivity measures (r 2, h 2, PLV, and MI) on data simulated from a combined biophysical/physiological model to generate realistic interictal epileptic spikes reflected in scalp EEG. We use a new network-based similarity index to compare between the network identified by each of the inverse/connectivity combination and the original network generated in the model. The method will be also applied on real data recorded from one epileptic patient who underwent a full presurgical evaluation for drug-resistant focal epilepsy. In simulated data, results revealed that the selection of the inverse/connectivity combination has a significant impact on the identified networks. Results suggested that nonlinear methods (nonlinear correlation coefficient, phase synchronization and mutual information) for measuring the connectivity are more efficient than the linear one (the cross correlation coefficient). The wMNE inverse solution showed higher performance than dSPM, cMEM and sLORETA. In real data, the combination (wMNE/PLV) led to a very good matching between the interictal epileptic network identified from noninvasive EEG recordings and the network obtained from connectivity analysis of intracerebral EEG recordings. These results suggest that source connectivity method, when appropriately configured, is able to extract highly relevant diagnostic information about networks involved in interictal epileptic spikes from non invasive dense-EEG data. PMID- 27549640 TI - Optically pumped subwavelength-scale metallodielectric nanopatch resonators. AB - We discuss subwavelength-scale semiconductor metal-optic resonators placed on the metal substrate with various top metal plate sizes. Albeit with large optical losses, addition of metal layers converts a leaky semiconductor nano-block into a highly-confined optical cavity. Optically pumped lasing action is observed with the extended top metal layer that can significantly suppress the radiation losses. Careful investigation of self-heating effects during the optical carrier injection process shows the importance of temperature-dependent material properties in the laser rate equation model and the overall laser performances. PMID- 27549641 TI - Co-Editors' Notes 29:2. PMID- 27549642 TI - Developing and pilot testing of a tool for "clinicosocial case study" assessment of community medicine residents. AB - BACKGROUND: Practical and clinical skills teaching should constitute a core part of the postgraduate curriculum of Community Medicine. The clinicosocial case study is a method to enhance learners' skills but there is no generally accepted organized system of formative assessment and structured feedback to guide students. A new tool based on the principles of mini-Clinical Evaluation Exercise (mini CEX) was developed and pilot tested as a 'clinicosocial case study' assessment of community medicine residents with feedback as a core component. METHODS: Ten core domains of clinicosocial skills were identified after reviewing the relevant literature and input from local experts in community medicine and medical education. We pilot tested the tool with eight faculty members to assess five residents during clinicosocial case presentations on a variety of topics. Kappa statistic and Bland Altman plots were used to assess agreement between faculty members' average assessment scores. Cronbach's alpha was used to test the internal consistency with faculty members as domains. RESULTS: All 95% confidence limits using the Bland-Altman method were within the predetermined limit of 2 points. The overall Kappa between two faculty members was fair ranging from 0.2 to 0.3. Qualitative feedback revealed that both faculty and residents were enthusiastic about the process but faculty suggested further standardization, while residents suggested streamlining of the process. DISCUSSION: This new assessment tool is available for objective and unbiased assessment of residents through 'clinicosocial case study,' which enriches learning through comprehensive feedback. Further validation in different settings is needed. PMID- 27549643 TI - Factors influencing medical students' self-assessment of examination performance accuracy: A United Arab Emirates study. AB - BACKGROUND: Assessment of one's academic capabilities is essential to being an effective, self-directed, life-long learner. The primary objective of this study was to analyze self-assessment accuracy of medical students attending the College of Medicine and Health Sciences, United Arab Emirates University, by examining their ability to assess their own performance on an MCQ examination. METHODS: 1 st and 2 nd year medical students (n = 235) self-assessed pre and post examination performance were compared with objectively measured scores (actual examination performance). Associations between accuracy of score prediction (pre and post assessment), and students' gender, year of education, perceived preparation, confidence and anxiety were also determined. RESULTS: Expected mark correlated significantly with objectively assessed marks (r = 0.407; P < 0.01) but with low predictability (R 2 = 0.166). The average objectively determined mark was 69% and the average expected mark was equivalent to 83%; indicating that students significantly overestimate their examination performance. Self-assessed pre-examination score range was significantly different between males and females (P < 0.05) with females expecting higher marks. Preparation and confidence correlated significantly with actual examination score (P < 0.05; r = 0.459 and 0.569 respectively). DISCUSSION: Gender, self-reported preparation and confidence are associated with self-assessment accuracy. Findings reinforce existing evidence indicating that medical students are poor self-assessors. There are potentially multiple explanations for misjudgment of this multidimensional construct that require further investigation and change in learning cultures. The study offers clear targets for change aimed at optimizing self-assessment capabilities. PMID- 27549644 TI - Reducing the physician workforce crisis: Career choice and graduate medical education reform in an emerging Arab country. AB - BACKGROUND: In today's interdependent world, issues of physician shortages, skill imbalances and maldistribution affect all countries. In the United Arab Emirates (UAE), a nation that has historically imported its physician manpower, there is sustained investment in educational infrastructure to meet the population's healthcare needs. However, policy development and workforce planning are often hampered by limited data regarding the career choice of physicians-in-training. The purpose of this study was to determine the specialty career choice of applicants to postgraduate training programs in the UAE and factors that influence their decisions, in an effort to inform educational and health policy reform. To our knowledge, this is the first study of career preferences for UAE residency applicants. METHODS: All applicants to residency programs in the UAE in 2013 were given an electronic questionnaire, which collected demographic data, specialty preference, and factors that affected their choice. Differences were calculated using the t-test statistic. RESULTS: Of 512 applicants, 378 participated (74%). The most preferred residency programs included internal medicine, pediatrics, emergency medicine and family medicine. A variety of clinical experience, academic reputation of the hospital, and international accreditation were leading determinants of career choice. Potential future income was not a significant contributing factor. DISCUSSION: Applicants to UAE residency programs predominantly selected primary care careers, with the exception of obstetrics. The results of this study can serve as a springboard for curricular and policy changes throughout the continuum of medical education, with the ultimate goal of training future generations of primary care clinicians who can meet the country's healthcare needs. As 65% of respondents trained in medical schools outside of the UAE, our results may be indicative of medical student career choice in countries throughout the Arab world. PMID- 27549646 TI - Using scientific inquiry to increase knowledge of vaccine theory and infectious diseases. AB - BACKGROUND: The aim of this study was to design and evaluate a laboratory activity based on scientific inquiry to educate first-year pharmacy students in the U.S. about vaccination theory and the attributes of common pathogens. METHODS: The laboratory activity had two principal sections. The first consisted of an interactive game during which students rolled a die to determine outcomes based on a set of pre-determined criteria. In the second section, students generated and tested hypotheses about vaccine theory using a computer simulation that modeled disease transmission within a large population. In each section students were asked to evaluate epidemiological data and make inferences pertinent to vaccination effectiveness. RESULTS: Mean scores on a knowledge-based assessment given immediately before and immediately after the activity increased from 46% to 71%. DISCUSSION: A laboratory activity designed to stimulate scientific inquiry within pharmacy students enabled them to increase their knowledge of common vaccines and infectious diseases. PMID- 27549645 TI - Teaching tobacco cessation to large student cohorts through train-the-trainers and problem based learning strategies. AB - BACKGROUND: Smoking is a leading cause of preventable deaths worldwide. Graduates of medical schools receive limited training on tobacco cessation and are ill equipped to treat tobacco dependence. In this paper, we describe and present evidence from an educational intervention based on a train-the-trainers model and problem-based learning strategy aimed to educate a large number of first-year medical students on tobacco-related issues. METHODS: A survey assessing students' knowledge, attitudes and beliefs was conducted before and after educational intervention. Tobacco experts from the faculty staff, who are trained problem based learning tutors, served as facilitators in the problem-based learning setting with 1000 medical students. RESULTS: Significant changes in knowledge and beliefs were observed. Items such as need for further training in cessation, importance, and effectiveness of brief advice showed significant variations after the educational intervention. DISCUSSION: Educational intervention based on a train-the-trainers and problem-based learning approaches are feasible and effective to educate a large cohort of first-year medical students in tobacco issues. Further research is needed to find out whether this intervention improves overall patient care management. PMID- 27549647 TI - Medical students' epistemological beliefs: Implications for curriculum. AB - BACKGROUND: Epistemological beliefs have a pervasive influence on learning and practice. Understanding these beliefs and how they develop, could play an important role in medical student training and shape later clinical practice. METHODS: The epistemological beliefs of first-year medical students from an Australian and Malaysian university were explored using a domain-specific instrument. RESULTS: There were significant differences between the disciplinary epistemological beliefs of Australian and Malaysian medical students across many items, and two specific factors (Certainty of Knowledge and Justification for Knowing). DISCUSSION: These findings have potential implications for teaching in biomedical disciplines and adaptation of Western curriculum innovations in Eastern educational contexts. Further work is needed to confirm and understand any epistemological differences and subsequent implications for learning and teaching in medicine. PMID- 27549648 TI - A medical school's approach to meeting the challenges of interdisciplinary global health education for resident physicians. AB - BACKGROUND: Following a similar trend among United States (US) medical students, US resident physicians are increasingly interested in pursuing global health education. Largely, residency education has lagged behind in addressing this demand. Time and curriculum requirements make meeting this need challenging. The Office of International Activities (OIA) at University of North Carolina-Chapel Hill (UNC-CH) was founded to provide support to students and residents in the area global health. In order to more fully understand resident physicians' attitudes and educational needs, a survey of incoming residents was undertaken. METHODS: The OIA administered a survey for incoming first-year residents of all specialties in July 2012. The survey was administered over one month using Qualtrics(r) and the response rate was 60%. RESULTS: Although 42% of residents had had an international experience during medical school, only 36% reported they felt prepared to address issues of international public health, including travel medicine and immigrant health. Significant barriers to involvement in global health opportunities in residency education were identified, including lack of time, finances and mentorship. DISCUSSION: As has been previously documented for global health education for medical students, this study's residents saw significant barriers to international electives during residency, including lack of elective time, finances and family responsibilities. In response to the survey results, an interdisciplinary educational initiative was developed at our school. This included obtaining buy-in from core residency leadership, establishing a pathway to arrange experiences, competitive scholarships for travel, and initiation of interdisciplinary educational opportunities. Results may serve as a useful model for other academic centers in developed countries. PMID- 27549649 TI - Reflective learning in community-based dental education. AB - BACKGROUND: Community-based dental education (CBDE) is the implementation of dental education in a specific social context, which shifts a substantial part of dental clinical education from dental teaching institutional clinics to mainly public health settings. Dental students gain additional value from CBDE when they are guided through a reflective process of learning. We propose some key elements to the existing CBDE program that support meaningful personal learning experiences. METHODS: Dental rotations of 'externships' in community-based clinical settings (CBCS) are year-long community-based placements and have proven to be strong learning environments where students develop good communication skills and better clinical reasoning and management skills. We look at the characteristics of CBDE and how the social and personal context provided in communities enhances dental education. RESULTS: Meaningfulness is created by the authentic context, which develops over a period of time. Structured reflection assignments and methods are suggested as key elements in the existing CBDE program. Strategies to enrich community-based learning experiences for dental students include: Photographic documentation; written narratives; critical incident reports; and mentored post-experiential small group discussions. A directed process of reflection is suggested as a way to increase the impact of the community learning experiences. DISCUSSION: We suggest key elements to the existing CBDE module so that the context-rich environment of CBDE allows for meaningful relations and experiences for dental students and enhanced learning. PMID- 27549650 TI - Lessons learned from the disruption of dental training of Malaysian students studying in Egypt during the Arab spring. AB - BACKGROUND: Political crisis and worsening security situation in Egypt in late 2013 resulted in Malaysian students who were pursuing their dental education in Egypt being recalled home to Malaysia. The Ministry of Higher Education in Malaysia took steps to integrate these students into public and private universities in Malaysia. METHODS: We used a questionnaire and informal interviews to learn from students returning from Egypt about their experiences transitioning from dental schools in Egypt to Malaysia. RESULTS: We discuss the challenges students faced with regards to credit transfer, pastoral care, the differences in the curriculum between the dental faculties of the two nations, and the financial implications of this disruption of their training. DISCUSSION: We live in a fragile world where similar political situations will surely arise again. The approaches used by the Malaysian government and the lessons learned from these students may help others. The perspectives of these students may help educators reintegrate expatriate students who are displaced by political instability back into the education system of their own countries. PMID- 27549651 TI - Educating medical students about military health: Perspectives from a multidisciplinary lecture initiative. AB - BACKGROUND: Medical student education on military health topics is critical in ensuring optimal future care for military service members and their families. METHODS: Keck School of Medicine of the University of Southern California (Keck SOM) students were invited to participate in an anonymous, voluntary, online survey ("Pre") rating their level of interest, awareness, exposure and comfort with military health issues on a 5-point Likert scale. A student-organized program of four voluntary lectures discussing military health-related topics was then implemented. Students were invited to re-take the survey ("Post") and also indicate which, if any, lectures they had attended. RESULTS: 230 students completed the "Pre" survey. A statistically significant deviation in responses was observed in all four questions, showing high interest (mean: 3.19 +/- 1.20, P = 0.002), low awareness (mean: 2.52 +/- 1.15, P < 0.001), low comfort (mean: 2.66 +/- 1.11, P < 0.001), and low exposure (mean: 1.80 +/- 0.95, P < 0.001) to military health issues. 132 students completed the "Post" survey, including 37 lecture attendees and 95 non-attendees. A statistically significant difference in the level of interest (P < 0.05) and exposure (P < 0.05) was observed between these groups. DISCUSSION: Medical schools that lack military health curricula may underprepare students to care for military-affiliated patients. Student-led programs can help introduce this topic before formalized curricula are instituted. PMID- 27549652 TI - A comparison of medical students', residents' and tutors' attitudes towards communication skills learning. AB - BACKGROUND: The consensus about the importance of communication skills in patient care does not guarantee that students and faculty perceive the usefulness of these skills. This study evaluated and compared medical students', residents' and tutors' attitudes towards learning communication skills, and examined the association with gender and year of residency. METHODS: We conducted a cross sectional survey with 492 participants (282 second-year students, 131 residents and 79 tutors). They completed the Communication Skills Attitude Scale (CSAS) and demographic/educational information. RESULTS: In general, participants showed positive attitudes towards learning communication skills. Medical students, residents and tutors did not differ on the Positive Attitudes Scale (CSAS-PAS). Residents scored higher than medical students on the Negative Attitudes Scale (CSAS-NAS) (P < 0.01). Females showed higher scores on the CSAS-PAS (P < 0.05) and lower scores on the CSAS-NAS (P < 0.01) than males in all subsamples. The effect sizes were medium. There were no significant differences according to year of residency. DISCUSSION: Medical students, residents and tutors consider training in communication skills an essential component for clinical practice and they agree about the need to learn these communication skills. Attention should be paid to measuring attitudes at all three levels of medical education in the design of communication skills courses. PMID- 27549653 TI - How do medical student journals fare? A global survey of journals run by medical students. AB - Medical students have made significant contributions to the medical and scientific fields in the past. Today, medical students still contribute to biomedical research; however, they often face disappointment from journals when trying to publish their findings. This led to the development of medical student journals, which take a more "student-friendly" approach. This article reviews the current medical student journals published in English and sheds light on current trends and challenges. PMID- 27549654 TI - Which peer teaching methods do medical students prefer? AB - BACKGROUND: The beneficial effects of peer teaching in medical education have been well-described in the literature. However, it is unclear whether students prefer to be taught by peers in small or large group settings. This study's aim was to identify differences in medical students' preferences and perceptions of small-group versus large-group peer teaching. METHODS: Questionnaires were administered to medical students in Year 3 and Year 4 (first 2 years of clinical training) at one institution in the United Kingdom to identify their experiences and perceptions of small-and large-group peer teaching. For this study, small group peer teaching was defined as a tutorial, or similar, taught by peer tutor to a group of 5 students or less. Large-group peer teaching was defined as a lecture, or similar, taught by peer tutors to a group of more than 20 students. RESULTS: Seventy-three students (81% response rate) completed the questionnaires (54% males; median age of 23). Nearly 55% of respondents reported prior exposure to small-group peer teaching but a larger proportion of respondents (86%) had previously attended large-group peer teaching. Of all valid responses, 49% did not have a preference of peer teaching method while 47% preferred small-group peer teaching. The majority of Year 3 students preferred small-group peer teaching to no preference (62.5% vs 37.5%, Fisher's exact test; P = 0.035) whereas most Year 4 students did not report a particular preference. Likert-scale responses showed that the majority of students held negative perceptions about large-group peer teaching, in comparison with small-group peer teaching, with respect to (1) interactivity, (2) a comfortable environment to ask questions, and (3) feedback received. DISCUSSION: Most respondents in this study did not report a preference for small-versus large-group settings when taught by peers. More Year 3 respondents were likely to prefer small-group peer teaching as opposed to Year 4 respondents. PMID- 27549655 TI - Implementing a centralized institutional peer tutoring program. AB - BACKGROUND: Peer tutoring has been found to be beneficial to both students and peer tutors in health sciences education programs. This article describes the implementation of a centralized, institutional peer tutoring program at the University of Mississippi Medical Center, an academic health science center in the U.S. The Program: This multispecialty peer tutoring program paired students experiencing academic difficulties with peer tutors who showed prior academic success, professionalism and effective communication skills. The program allowed students and peer tutors to coordinate their own tutoring services. PROGRAM EVALUATION: Evaluations by both students and peer tutors showed satisfaction with the program. RECOMMENDATIONS: Recommendations for developing and implementing an effective peer tutoring program are presented, including utilization of an online system, consistent program policy with high professionalism expectations, funding, program evaluation and data tracking. PMID- 27549656 TI - Self-directed learning modules of CT scan images to improve students' perception of gross anatomy. AB - BACKGROUND: A contemporary anatomy curriculum that aims to be clinically relevant requires medical students to be introduced to radiological anatomy in the preclinical years. Ideally, the curriculum should also support self-directed learning, a habit best instilled early. Based on these educational requirements, we designed an interesting and clinically-meaningful program of self-learning modules in radiological anatomy to augment students' learning of gross anatomy. The program is guided by current theories of learning, which emphasize an individualized learning pace for students. METHODS: This program uses enlarged computerized tomography (CT) scan images and associated resource materials. Scans are posted on the first day of the week in a public area for students to review on their own time. On the second day penciled outlines of important structures are provided to help students identify structures, and students are encouraged to discuss the images with faculty. On the last day of the week the identity of the structures are revealed to students. RESULTS: An open-ended questionnaire used to evaluate the program revealed that 95.5% of students used the program and a great majority recommended the program should be continued for future students. DISCUSSION: The present program enhances learning of gross anatomical relations through having students use visual clues in logically interpreting unlabeled CT scans in an organized and sequential way. The program promotes self-directed learning. In addition to its use with preclinical students, the modules might also help students in the clinical phase of the curriculum bolster their knowledge of spatial anatomy. PMID- 27549657 TI - Simulation and lessons learned from the Ebola epidemic. PMID- 27549658 TI - Community medicine teaching for paramedical courses in India: Does the curriculum for medical laboratory technology course need a revision? PMID- 27549659 TI - Understanding culture in higher education in Thailand. PMID- 27549660 TI - The use of a "rim cutter" device and a flanged cup for improving the mantle of the acetabular component of a cemented Exeter total hip arthroplasty. AB - A retrospective study was performed to evaluate the cement mantle in two groups of patients treated with the acetabular components of cemented Exeter total hip arthroplasties (THAs). Two groups of 20 patients were compared: Group 1 received non-flanged acetabular cemented cups (Contemporary, Stryker) and Group 2 received flanged acetabular cemented cups (X3 Rim Fit, Stryker). Cups in Group 2 were implanted after using a rim cutter device. Group 2 showed better penetration of cement in zone 1 (10.76 mm compared with 2.93 mm; p = 0.008) and a thicker cement mantle in zone 1 (3.57 mm compared with 2.89 mm; p = 0.04). More cups in Group 2 had a cement mantle thickness less than 3 mm (30 % in Group 1 compared with 70 % in Group 2; p = 0.0039). No other radiological differences were observed. These results favor the use of a rim cutter device and flanged cup to improve the cement mantle for the acetabular components of cemented Exeter THAs. However, the improvements were less than expected. In view of the results of previous studies, further research is therefore needed to assess the value of this approach in improving the acetabular cement mantle. PMID- 27549661 TI - The effect of sublaminar wires on the rib hump deformity during scoliosis correction manoeuvres. AB - INTRODUCTION: During thoracic curve correction, the tightening of the sublaminar wires through concavity creates a medial and a dorsal translation of the spine. However, little is known about the effect of the sublaminar wires on the axial plane. METHODS: This is prospective case series analysis of 30 consecutive surgical patients with main thoracic adolescent idiopathic scoliosis. All of the patients were fused with hybrid instrumentation (apical concavity-sublaminar wires) and differential rod contouring (over-kyphosis concavity/under-kyphosis convexity). The degrees of the rib hump were measured with a scoliometer placed at the apex of the deformity at five different times: (1) preoperatively through the Adam's test, and during surgery (sterilised scoliometer), (2) with the patient lying prone, (3) after the Ponte osteotomies, (4) after the apical sublaminar tightening, and (5) after convexity apical derotation and compression manoeuvres. RESULTS: (1) Preoperatively, the Adam's test was 16.3 degrees +/- 4.6. (2) Lying prone and under general anaesthesia, it decreased to 11.4 degrees +/- 3.9. (3) After exposure and Ponte osteotomies, it was 7.1 degrees +/- 4. (4) After the wire tightening, it was 10.8 degrees +/- 4.7. (5) After the convexity manoeuvres, it was 4.8 degrees +/- 3.7. The degrees of the rib hump final correction were 11.6 degrees +/- 4 (70 % correction). The tightening of the sublaminar wires increased the rib hump by 3.5 degrees . CONCLUSIONS: The sublaminar wire tightening towards the concave rod seemed to create an effect opposite of the desired effect, increasing the apical rotation and the thoracic rib hump deformity. Convexity manoeuvres (apical screw derotation and compression) are necessary and must be coupled with an under-bending of the convex rod to neutralise this effect. PMID- 27549663 TI - Mesenchymal stromal cells: properties and role in management of cutaneous diseases. AB - This review describes the current understanding and the potential use of mesenchymal stromal cells (MSCs) in cell-based therapies for clinical management of difficult wounds and other dermatoses. MSCs have been shown to possess many advantageous properties that make them a promising therapeutic modality in dermatology still under investigation. In fact, MSCs' ability to promote wound healing through its paracrine function and pro-angiogenic properties have generated increasing interest for treating acute and chronic wounds. There is also great interest in utilizing MSCs' immunological characteristics for therapeutic use especially for patients with debilitating systemic autoimmune and inflammatory skin conditions who have failed other therapies. Its role in aesthetics has also been explored with clinical data showing improvement of acne scars and wrinkles from photoaging. Clinical trials are underway investigating the safety and efficacy of MSCs in the treatment of different skin conditions such as acute burns, diabetic and venous stasis ulcers, epidermolysis bullosa and systemic sclerosis, among others. We anticipate that as our understanding of the characteristics and function of MSCs grow, so will its role in cell-based treatments of dermatological conditions. PMID- 27549664 TI - Influence of External Pressure on the Performance of Quantum Dot Solar Cells. AB - We report the influence of post-treatment via the external pressure on the device performance of quantum dot (QD) solar cells. The structural analysis together with optical and electrical characterization on QD solids reveal that the external pressure compacts QD active layers by removing the mesoscopic voids and enhances the charge carrier transport along QD solids, leading to significant increase in JSC of QD solar cells. Increasing the external pressure, by contrast, accompanies reduction in FF and VOC, yielding the trade-off relationship among JSC and FF and VOC in PCE of devices. Optimization at the external pressure in the present study at 1.4-1.6 MPa enables us to achieve over 10% increase in PCE of QD solar cells. The approach and results show that the control over the organization of QDs is the key for the charge transport properties in ensemble and also offer simple yet effective mean to enhance the electrical performance of transistors and solar cells using QDs. PMID- 27549662 TI - Functional genomic analyses of Enterobacter, Anopheles and Plasmodium reciprocal interactions that impact vector competence. AB - BACKGROUND: Malaria exerts a tremendous socioeconomic impact worldwide despite current control efforts, and novel disease transmission-blocking strategies are urgently needed. The Enterobacter bacterium Esp_Z, which is naturally harboured in the mosquito midgut, can inhibit the development of Plasmodium parasites prior to their invasion of the midgut epithelium through a mechanism that involves oxidative stress. Here, a multifaceted approach is used to study the tripartite interactions between the mosquito, Esp_Z and Plasmodium, towards addressing the feasibility of using sugar-baited exposure of mosquitoes to the Esp_Z bacterium for interruption of malaria transmission. METHODS: The ability of Esp_Z to colonize Anopheles gambiae midguts harbouring microbiota derived from wild mosquitoes was determined by qPCR. Upon introduction of Esp_Z via nectar feeding, the permissiveness of colonized mosquitoes to Plasmodium falciparum infection was determined, as well as the impact of Esp_Z on mosquito fitness parameters, such as longevity, number of eggs laid and number of larvae hatched. The genome of Esp_Z was sequenced, and transcriptome analyses were performed to identify bacterial genes that are important for colonization of the mosquito midgut, as well as for ROS-production. A gene expression analysis of members of the oxidative defence pathway of Plasmodium berghei was also conducted to assess the parasite's oxidative defence response to Esp_Z exposure. RESULTS: Esp_Z persisted for up to 4 days in the An. gambiae midgut after introduction via nectar feeding, and was able to significantly inhibit Plasmodium sporogonic development. Introduction of this bacterium did not adversely affect mosquito fitness. Candidate genes involved in the selection of a better fit Esp_Z to the mosquito midgut environment and in its ability to condition oxidative status of its surroundings were identified, and parasite expression data indicated that Esp_Z is able to induce a partial and temporary shutdown of the ookinetes antioxidant response. CONCLUSIONS: Esp_Z is capable of inhibiting sporogonic development of Plasmodium in the presence of the mosquito's native microbiota without affecting mosquito fitness. Several candidate bacterial genes are likely mediating midgut colonization and ROS production, and inhibition of Plasmodium development appears to involve a shutdown of the parasite's oxidative defence system. A better understanding of the complex reciprocal tripartite interactions can facilitate the development and optimization of an Esp_Z-based malaria control strategy. PMID- 27549666 TI - Moyamoya Disease: A Review of Clinical Research. AB - About 5 decades have passed since the concept of moyamoya disease (MMD) was established in Japan. In that time, many clinical MMD studies have been performed from several different points of view, such as epidemiology, pathophysiology, surgical procedures, and prognosis. In addition, rapid developments in MMD genetic analysis have occurred. In light of all this activity, clinicians must continually update their knowledge of MMD in order to improve the prognosis of MMD patients. In this review article, we summarize the clinical MMD studies and introduce cutting-edge findings regarding MMD. PMID- 27549665 TI - Is population flow an unintended consequence of alcohol management plans? AB - AIMS AND OBJECTIVES: The aim of this study was to gauge whether, and to what extent, population flow occurred as a result of the implementation of alcohol management plans in Indigenous communities. BACKGROUND: Alcohol management plans involving carriage limits and dry places were introduced into 15 Queensland Indigenous communities between 2002-2004. Controls on alcohol availability were further tightened between 2008-2010, seeing the closure of eight mainly remote community taverns/canteens. DESIGN: A retrospective observational study was undertaken using data from the Queensland Injury Surveillance Unit. METHODS: Population flow was measured by changing patterns of alcohol-related injuries in a mining region near dry Indigenous communities following the introduction of alcohol management plans and a control mining region distant from Indigenous communities with alcohol management plans. Data were analysed using descriptive and inferential statistics. Logistic regression was used for the comparison of the characteristics between the emergency department presentations. The rates of alcohol-related injury presentations per 1000/population were calculated and age standardised to the Australian population. RESULTS: Between the five-year periods 2003-2007 and 2008-2012, alcohol-related injury presentations to the Mount Isa emergency department trebled from an age-adjusted average annual rate of 9.5/1000 in the region's population to 27.1/1000 population. In the control region, alcohol-related emergency department injury presentations did not increase to the same degree with age-adjusted average annual rates of 1.42/1000 and 2.21/1000, respectively. CONCLUSIONS: The 10-year pattern of emergency department presentations for alcohol-related injuries increased significantly in the Mount Isa region compared with the control region. Further research should investigate the impacts of population flow related to Indigenous community alcohol management plans. RELEVANCE TO CLINICAL PRACTICE: Although initiatives such as alcohol management plans have been implemented to reduce alcohol use and related consequences in Indigenous communities, there needs to be a greater consideration of the impact of these policies in nearby towns in the future. PMID- 27549667 TI - The Usefulness of CT-Diffusion Weighted Image Mismatch in Patients with Mild to Moderate Traumatic Brain Injury. AB - Traumatic brain injury (TBI) has a complex and heterogeneous pathology. It is frequently difficult to predict the neurological deterioration of patients with TBI, and unpredictable change may occur even when TBI is mild to moderate. When computed tomography (CT) findings are considered to be inconsistent with the traumatic origin or with the neurological deterioration of patients observed on admission, magnetic resonance imaging (MRI) is employed based on the standards of our ethical committee. In this retrospective study, we compared CT and diffusion weighted imaging (DWI) of patients with mild to moderate TBI in the very acute phase. When the high-intensity lesions on DWI are larger than the high-density lesions on CT images, we defined the imaging finding as a 'CT-DWI mismatch'. Between January 2010 and December 2013, 92 patients were inspected using both CT and MRI at admission, and we detected a CT-DWI mismatch in 35 patients. CT-DWI mismatch was 92.6% (95% confidence interval 79.8-97.9) sensitive and 84.6% (95% confidence interval 79.3-86.3) specific for the prediction of enlargement of the hemorrhagic lesions on repeat CT. CT-DWI mismatch is considered to be useful as one of the predictors of the enlargement of hemorrhagic lesions in patients with mild to moderate TBI. PMID- 27549668 TI - Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation. AB - Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p< 0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation. PMID- 27549669 TI - Validity of Mothers' Reports of Children's Weight in Japan. AB - Estimation methods for pediatric weight have not been evaluated for Japanese children. This study aimed to assess the accuracy of mothers' reports of their children's weight in Japan. We also evaluated potential alternatives to the estimation of weight, including the Broselow tape (BT), Advanced Pediatric Life Support (APLS), and Park's formulae. We prospectively collected cross-sectional data on a convenience sample of 237 children aged less than 10 years who presented to a general pediatric outpatient clinic with their mothers. Each weight estimation method was evaluated using Bland- Altman plots and by calculating the proportion within 10% and 20% of the measured weight. Mothers' reports of weight were the most accurate method, with 94.9% within 10% of the measured weight, the lowest mean difference (0.27kg), and the shortest 95% limit of agreement (-1.4 to 1.9kg). The BT was the most reliable alternative, followed by APLS and Park's formulae. Mothers' reports of their children 's weight are more accurate than other weight estimation methods. When no report of a child's weight by the mother is available, BT is the best alternative. When an aged-based formula is the only option, the APLS formula is preferred. PMID- 27549670 TI - A Diagnostic Algorithm for Eosinophilic Granulomatosis with Polyangiitis Initially Diagnosed as Lumbar Disc Hernia or Lumbar Spinal Stenosis: Personal Experience and Review of the Literature. AB - Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic vasculitis and is difficult to diagnose. EGPA has a number of symptoms including peripheral dysesthesia caused by mononeuropathy multiplex, which is similar to radiculopathy due to lumbar disc hernia or lumbar spinal stenosis. Therefore, EGPA patients with mononeuropathy multiplex often visit orthopedic clinics, but orthopedic doctors and spine neurosurgeons have limited experience in diagnosing EGPA because of its rarity. We report a consecutive series of patients who were initially diagnosed as having lumbar disc hernia or lumbar spinal stenosis by at least 2 medical institutions from March 2006 to April 2013 but whose final diagnosis was EGPA. All patients had past histories of asthma or eosinophilic pneumonia, and four out of five had peripheral edema. Laboratory data showed abnormally increased eosinophil counts, and nerve conduction studies of all patients revealed axonal damage patterns. All patients recovered from paralysis to a functional level after high-dose steroid treatment. We shortened the duration of diagnosis from 49 days to one day by adopting a diagnostic algorithm after experiencing the first case. PMID- 27549671 TI - Erythroblastosis of the Donor Twin of Twin Anemia-Polycythemia Sequence. AB - Twin anemia-polycythemia sequence (TAPS) is a group of disorders in monochorionic twins characterized by a large intertwin hemoglobin difference without amniotic fluid discordance. Reticulocyte count is used to diagnose this condition, but little is known about the role of erythroblasts, which are the prior stage of reticulocytes. In the present case of TAPS, the 25-yr-old Japanese mother showed no signs of oligohydramnios or polyhydramnios throughout gestation. The twins were born at 36 weeks and 6 days, weighing 2,648g and 1,994g. The intertwin hemoglobin difference in umbilical cord blood was (21.1-5.0=) 16.1g/dL and the donor twin showed signs of chronic anemia, including myocardial hypertrophy and pericardial effusion. Erythroblastosis of the donor twin was prolonged (53,088.5, 42,114.8 and 44,217.9/MUL on days 0, 1 and 2, respectively). Erythroblastosis, which indicates chronic anemia, is also a good diagnostic indicator of TAPS. PMID- 27549672 TI - Heerfordt's Syndrome Associated with a High Fever and Elevation of TNF-alpha. AB - Heerfordt's syndrome is a rare manifestation of sarcoidosis and is defined as a combination of facial palsy, parotid swelling, and uveitis, associated with a low grade fever. We report a case of Heerfordt's syndrome presenting with a high fever and increased serum tumor necrosis factor alpha (TNF-alpha) levels. The patient had facial palsy, parotid swelling, uveitis, and swelling of the right supraclavicular and hilar lymph nodes. Corticosteroid therapy was initiated, and her symptoms soon resolved completely, in tandem with a decrease in TNF-alpha serum levels. PMID- 27549673 TI - A Rare Case of Diffuse Large B-cell Lymphoma in a Patient with IgG4-Related Autoimmune Pancreatitis. AB - A 61-year-old Japanese man with IgG4-related autoimmune pancreatitis was referred to our hospital because of perspiration during food intake. Abdominal computed tomography (CT) with contrast media revealed multiple mesenteric lymphadenopathies. An open surgical abdominal biopsy and subsequent histopathological analysis revealed abnormally large lymphoid cells that were negative for CD3, CD5, and c-myc and positive for CD20 and bcl-2, leading to a diagnosis of diffuse large B-cell lymphoma. Here, we discuss the risk of malignancies, particularly malignant lymphoma in patients with IgG4-related disease. The importance of pathological analysis to reach the appropriate diagnosis in such cases should be emphasized. PMID- 27549674 TI - A Case of Focal Bone Marrow Reconversion Mimicking Bone Metastasis: The Value of 111Indium Chloride. AB - We present a case of a 66-year-old man with esophageal carcinoma. 18Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for evaluating distant metastasis and staging revealed 18F-FDG uptake in the third lumbar vertebra and other vertebrae. Magnetic resonance imaging could not differentiate bone metastases from benign bone lesions. We considered the possibility of bone marrow reconversion. 111Indium chloride (111In-Cl3) scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) revealed erythroid bone marrow components in the bone lesions. The diagnosis of bone marrow reconversion was pathologically confirmed by a bone biopsy of the third lumbar vertebra. The patient underwent esophagectomy and has remained disease-free in the 2 years since. To the best of our knowledge, this is the first report to describe the usefulness of 111In-Cl3 with SPECT/CT for the diagnosis of bone marrow reconversion. PMID- 27549675 TI - Autologous Blood Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation. AB - Temporomandibular joint (TMJ) dislocation can occur during daily activities and negatively affect a patient's quality of life. Although both nonsurgical and surgical techniques have been used to treat recurrent TMJ dislocation, the former is not always successful and the latter, although having a high success rate, is invasive and requires hospitalization. Recently, autologous blood injection has been used to treat recurrent TMJ dislocation. However, this technique is not yet widely used in clinical practice. We designed this study to obtain further information as to efficacy, safety and stability of autologous blood injection for recurrent TMJ dislocation. PMID- 27549676 TI - The Efficacy of Rituximab in High-risk Renal Transplant Recipients. AB - Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients. PMID- 27549677 TI - A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis. AB - Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants. PMID- 27549678 TI - Safety of Percutaneous Cryoablation in Patients with Painful Bone and Soft Tissue Tumors: A Single Center Prospective Study (SCIRO-1502). AB - This single center prospective study is being conducted to evaluate the safety of the cryoablation for patients with pathologically diagnosed painful bone and soft tissue tumors. Enrollment of 10 patients is planned over the 3-year recruitment period. Patients have related local pain after receiving medications or external radiation therapies will be included in this study. Cryoablation will be percutaneously performed under imaging guidance, and a temperature sensor will be used during treatment as necessary. The primary endpoint is prevalence of severe adverse events within 4 weeks after therapy. The secondary endpoint is effectiveness 4 weeks after the procedure. PMID- 27549679 TI - An Open-Label Feasibility Trial of Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depressive Episodes. AB - Repetitive transcranial magnetic stimulation (rTMS) has been reported to be a new treatment option for treatment-resistant depression. In Japan, there has been limited research into its feasibility, efficacy, and tolerability. We have launched a trial of rTMS for treating medication-resistant major depressive disorder and bipolar depression. We are investigating low-frequency rTMS to the right dorsolateral prefrontal cortex and traditional high-frequency rTMS to the left dorsolateral prefrontal cortex, in 20 patients. The primary outcome of the study is the treatment completion rate. This study will provide new data on the usefulness of rTMS for treatment-resistant depression in Japan. PMID- 27549680 TI - Efficacy and Safety of Endoscopic Ultrasound-guided Ethanol Ablation Therapy for Pancreatic Neuroendocrine Tumors. AB - Recently, endoscopic ultrasonography (EUS)-guided ethanol ablation for small pancreatic neuroendocrine tumors (p-NETs) has been reported. However, the efficacy and safety of the technique remain unclear. We have launched a prospective pilot study of EUS-guided ethanol ablation for p-NETs. The major eligibility criteria are the presence of a pathologically diagnosed grade (G) 1 or G2 p-NET, a tumor size of 2cm, and being a poor candidate for surgery. A total of 5 patients will be treated. The primary endpoint will be the complete ablation rate at 1 month after treatment. PMID- 27549681 TI - Single Center Prospective Phase II Trial of CT-guided Radiofrequency Ablation for Pulmonary Metastases from Colorectal Cancer (SCIRO-1401). AB - The present single center prospective phase II clinical trial is designed to evaluate the efficacy and safety of percutaneous radiofrequency (RF) ablation for colorectal lung metastases. Patients who have colorectal lung metastases without extrapulmonary metastases are included in this study. The primary endpoint is 3 year overall survival (OS) after RF ablation. The secondary endpoints are the prevalence of adverse events within 4 weeks, local tumor progression rate, 1- and 5-year OS, cause-specific survival, and relapse-free survival. The recruitment of patients commenced in July 2014, and the enrolment of 45 patients is intended over the 3 years of study period. PMID- 27549682 TI - Diagnosing Pancreatic Tumors Using Contrast-enhanced Harmonic Endoscopic Ultrasonography with Sonazoid. AB - Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with contrast agent enabled us to assess the hemodynamics closely, despite limited data in pancreatic tumors. We have initiated a prospective, single arm, and non randomized study to clarify the accuracy and safety of CH-EUS with Sonazoid and time-intensity curve (TIC) analysis for diagnosing benign or malignant pancreatic tumors. A total of 200 patients will undergo CH-EUS and TIC analysis. Receiver operating characteristic (ROC) analysis will be used to determine the optimal parameter cutoff values for TIC analysis. This will clarify whether CH-EUS and TIC can further improve the diagnosis of pancreatic tumors over conventional EUS. PMID- 27549683 TI - Study about the Efficacy of Metformin to Immune Function in Cancer Patients. AB - A study to evaluate the effect of metformin on the immune system was commenced in July 2014. Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and previous studies have reported that metformin has an anti-tumor effect. The aim of this study is to evaluate the efficacy of metformin on the immune system in human cancer patients in vivo. The primary outcome parameter will be the rate change in the population of CD8+ T cells, which produce multiple cytokines. PMID- 27549684 TI - Viral bronchiolitis. AB - Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure. PMID- 27549685 TI - Neonatal clavicle fracture in cesarean delivery: incidence and risk factors. AB - BACKGROUND: Neonatal clavicle fracture in cesarean delivery is rare and has not been extensively studied. METHODS: We performed a retrospective review of cesarean deliveries with neonatal clavicle fracture during a 12-year period. Maternal and neonatal factors as well as surgical factors related to cesarean delivery for the fracture were determined and compared to the control group to analyze their significance. RESULTS: Among a total 89 367 deliveries during the study period, 36 286 babies were born via cesarean section. Nineteen cases of clavicle fractures in cesarean section were identified (0.05% of total live births via cesarean section). In the analysis of maternal and neonatal risk factors, birthweight, birthweight >= 4000 g and maternal age were significantly associated with clavicle fracture in cesarean section. However, clavicle fractures were not correlated with the selected surgical factors such as indication for cesarean section, skin incision to delivery time and incision type of skin and uterus. Logistic regression analysis showed that birthweight was the major risk factor for clavicle fracture. CONCLUSION: Clavicle fractures complicated 0.05% of cesarean deliveries. The main risk factor related to a clavicle fracture in cesarean section was the birthweight of an infant. As reported in previous studies associated with vaginal delivery, clavicle fracture is considered to be an unavoidable event and may not be eliminated, even in cesarean delivery. PMID- 27549686 TI - Complications of subdural and depth electrodes in 269 patients undergoing 317 procedures for invasive monitoring in epilepsy. AB - OBJECTIVE: Intracranial monitoring is fundamental to epilepsy surgery, with reported complication rates of 3-17%. We aimed to assess the differences in complication rates between subdural and depth electrodes. METHODS: We conducted a retrospective review of 317 electrode implantation procedures. All documented abnormal postoperative findings were recorded in our study. Those that resulted in a significant alteration of treatment course, including neurologic deficit, long-term medication use, reoperation, or hospital readmission, were deemed clinically significant. When possible, findings were attributed to a particular electrode type based on relative location to each electrode. RESULTS: Postoperative abnormalities were associated with SDE placement in 152 (47.9%) procedures and 40 (25.2%) DE placements (p < 0.001). Twenty-nine (9.1%) clinically significant complications were seen in the subdural electrode (SDE) group compared to 10 associated with DEs (6.3%, p = 0.37). SDEs were associated with increased rates of any postoperative hemorrhage (p < 0.001) or extraaxial collection (p = 0.007). Subdural grid placement was associated with an increased risk of any extraaxial collection (odds ratio [OR 2.42), as well as clinically significant collections (OR 9.47). Previous craniotomy was found to be associated with any abnormal postoperative finding (OR 1.71) as well as radiographic hemorrhage (OR 1.99). Concurrent resection is also associated with abnormal findings (OR 1.83) and extraaxial collections (OR 2.37). The overall complication rate was 9.1%, with 13 procedures (4.1%) resulting in neurologic deficit. However, only two patients (0.6%) had permanent neurologic sequelae resulting from lead placement. SIGNIFICANCE: Subdural electrodes appear to have an increased rate of abnormal postoperative findings, including hemorrhage and extraaxial collections; however, there was no difference in clinically significant findings. Subdural grids also appear to be associated with symptomatic extraaxial collections, and previous craniotomy increases the risk of hemorrhage. Overall, intracranial monitoring remains a safe and effective procedure for localization of operative seizure foci. Patient selection and risk education for various modalities is an essential aspect of preoperative evaluation. PMID- 27549687 TI - Potential Effect of Substituting Estimated Glomerular Filtration Rate for Estimated Creatinine Clearance for Dosing of Direct Oral Anticoagulants. AB - OBJECTIVES: To determine the potential effect of substituting glomerular filtration rate (GFR) estimates for renal clearance estimated using the Cockcroft Gault method (CrCL-CG) to calculate direct oral anticoagulant (DOAC) dosing. DESIGN: Simulation and retrospective data analysis. SETTING: Community, academic institution, nursing home. PARTICIPANTS: Noninstitutionalized individuals aged 19 to 80 from the National Health and Nutrition Examination Survey (NHANES) (2011/12) (n = 4,687) and medically stable research participants aged 25 to 105 (n = 208). MEASUREMENTS: Age, height, weight, sex, race, serum creatinine, CrCL CG, and GFR (according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations). Outcome measures were dosing errors if GFR were to be substituted for CrCL-CG. RESULTS: Renal clearance estimates according to all methods were highly correlated (P < .001), although at lower clearances, substitution of GFR estimates for CrCL-CG resulted in failure to recognize needs for dose reductions of rivaroxaban or edoxaban in 28% of NHANES subjects and 47% to 56% of research subjects. At a CrCL-CG of less than 30 mL/min, GFR estimates missed indicated dosage reductions for dabigatran in 18% to 21% of NHANES subjects and 57% to 86% of research subjects. Age and weight contributed to differences between renal clearance estimates (P < .001), but correction of GFR for body surface area (BSA) did not reduce dosing errors. At a CrCL-CG greater than 95 mL/min, edoxaban is not recommended, and GFR esimates misclassified 24% of NHANES and 39% of research subjects. Correction for BSA reduced misclassification to 7% for NHANES and 14% in research subjects. CONCLUSION: Substitution of GFR estimates for estimated CrCl can lead to failure to recognize indications for reducing DOAC dose and potentially higher bleeding rates than in randomized trials. PMID- 27549729 TI - Undergraduate experience and self-assessed confidence in paediatric dentistry at the University of Jordan Dental School. AB - INTRODUCTION: The aims of the study were to audit the number and types of clinical procedures completed by the undergraduate dental students in the paediatric dentistry course at the University of Jordan Dental School and to present data on self-reported confidence in a variety of aspects of paediatric dentistry. MATERIALS AND METHODS: A retrospective audit of clinical logbooks for the entire class of 120 dental students in their fifth clinical year was performed. Key clinical procedures performed in the paediatric clinics were recorded including treatment performed on both primary and permanent teeth. Students were requested to complete an anonymous questionnaire to assess confidence related to six activities using a visual analogue scale (VAS). RESULTS: All students performed restorations in primary teeth with the majority providing approximal restorations (91%), pit and fissure restorations (89%) followed by stainless steel crowns (81%). In addition, all students performed a pulpotomy for a primary tooth, extraction of a primary tooth and fissure sealants. Only a quarter of the students treated a traumatised incisor. Students considered themselves most confident (VAS >= 7) in performing operative dentistry, examination, diagnosis and treatment planning and providing preventive therapy. They were least confident in the management of dento-alveolar trauma (VAS = 3.8). CONCLUSION: Students at the University of Jordan Dental School were found to have good experience of clinical paediatric operative dentistry with the majority performing pulp therapy, preformed crowns and extractions. Deficiencies have been reported in student exposure to dental trauma, and these are being addressed. PMID- 27549730 TI - Protein Losing Enteropathy After Cardiac Transplantation Successfully Treated by Stent Implantation. AB - Protein losing enteropathy (PLE) is a severe consequence of Fontan physiology that sometimes requires heart transplantation for definitive treatment. We describe transplant refractory PLE in a patient with heterotaxia and complex systemic and hepatic venous connections, successfully treated by transcatheter relief of multiple venous obstructions. PMID- 27549731 TI - Extracorporeal Life Support in Multisystem Smooth Muscle Dysfunction Syndrome. AB - We describe an infant with congenital mydriasis, patent ductus arteriosus (PDA), pulmonary hypertension, and cystic lung disease. She had all the major components of multisystemic smooth muscle dysfunction syndrome. Due to progressive respiratory deterioration, she required surgical PDA interruption, extracorporeal life support, and subsequent prolonged respiratory support. Genetic testing revealed ACTA2 R179H mutation and cystic lung disease on biopsy. PMID- 27549732 TI - Incidental Finding of Right Coronary Artery to Pulmonary Artery Fistula During Surgical Repair of Aortic Arch Atresia in Turner Syndrome. AB - Aortic arch atresia has not been associated with coronary anomalies. We present a unique case of a patient with Turner syndrome and aortic arch atresia with the incidental finding of a right coronary artery to pulmonary artery fistula at the time of surgical repair. PMID- 27549733 TI - Absent Pulmonary Valve Syndrome With Tricuspid Atresia, Ventricular Septal Defect, and Aneurysmal Dilated Pulmonary Artery: A Case Report of Successful Fontan Completion. AB - Of the associated cardiac defects with absent pulmonary valve, the combination of tricuspid atresia, ventricular septal defect, and aneurysmal dilatation of the pulmonary arteries is very rare. We report the case of a low-birth-weight girl (2,282 g) with this anomaly, which was prenatally diagnosed. Fontan completion was successfully achieved at 16 months of age, following staged palliative procedures including banding of the main pulmonary trunk and plication of the aneurysmal dilated central pulmonary artery. PMID- 27549734 TI - A Rare Cause of Pediatric Stroke. AB - We describe a case of sudden-onset left-sided hemiparesis and dysarthria in a five-year-old boy. Acute vascular malformation bleeding or ischemic stroke was suspected. Neurological examination three weeks after the initial event revealed mild residual facial paresis. Brain angiography ruled out a vascular malformation. A work-up echocardiogram revealed a 4-cm left atrial mass compatible with cardiac myxoma. Urgent surgical resection of the mass under cardiopulmonary bypass confirmed the diagnosis. Uneventful recovery followed surgical resection. In this report, we present a partially embolized left atrial myxoma that caused an acute ischemic stroke, which is rarely considered and encountered in the pediatric population. PMID- 27549735 TI - A population-based study of cellular markers in R-CHOP treated diffuse large B cell lymphoma patients. AB - AIM: To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP. PATIENTS AND METHODS: The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012. RESULTS: Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa) >= 2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa >=2 (p = 0.002), Ki-67 >= 70% (p = 0.04) and p53 overexpression >=50% (p = 0.02) were associated with inferior LSS and OS. Co expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p = 0.0002), OS (p = 0.009) and PFS (p = 0.03). In addition, triple expression of MYC, BCL-2 and BCL 6, also correlated with a significantly inferior LSS (p = 0.02). CONCLUSION: Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression. PMID- 27549736 TI - Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma. AB - The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 * 10(-6), P = 0.028 and P = 3.2 * 10(-5)) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis. PMID- 27549737 TI - Barcoding lichen-forming fungi using 454 pyrosequencing is challenged by artifactual and biological sequence variation. AB - Although lichens (lichen-forming fungi) play an important role in the ecological integrity of many vulnerable landscapes, only a minority of lichen-forming fungi have been barcoded out of the currently accepted ~18 000 species. Regular Sanger sequencing can be problematic when analyzing lichens since saprophytic, endophytic, and parasitic fungi live intimately admixed, resulting in low-quality sequencing reads. Here, high-throughput, long-read 454 pyrosequencing in a GS FLX+ System was tested to barcode the fungal partner of 100 epiphytic lichen species from Switzerland using fungal-specific primers when amplifying the full internal transcribed spacer region (ITS). The present study shows the potential of DNA barcoding using pyrosequencing, in that the expected lichen fungus was successfully sequenced for all samples except one. Alignment solutions such as BLAST were found to be largely adequate for the generated long reads. In addition, the NCBI nucleotide database-currently the most complete database for lichen-forming fungi-can be used as a reference database when identifying common species, since the majority of analyzed lichens were identified correctly to the species or at least to the genus level. However, several issues were encountered, including a high sequencing error rate, multiple ITS versions in a genome (incomplete concerted evolution), and in some samples the presence of mixed lichen-forming fungi (possible lichen chimeras). PMID- 27549738 TI - TGF-beta/BAMBI pathway dysfunction contributes to peripheral Th17/Treg imbalance in chronic obstructive pulmonary disease. AB - BMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor beta (TGF-beta) signaling. Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated. In this study, we investigated whether TGF-beta/BAMBI pathway is associated with COPD. Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients. Elevated Th17/Treg ratios, and increased levels of BAMBI protein and mRNA (in plasma and CD4(+) T cells respectively), were observed in COPD compared with HC and HS. BAMBI expression was first observed on human CD4(+) T cells, with a typical membrane-bound pattern. The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-beta1 levels and Th17/Treg ratio. Together, an impaired TGF-beta/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD. PMID- 27549739 TI - Pseudomonas spp. diversity is negatively associated with suppression of the wheat take-all pathogen. AB - Biodiversity and ecosystem functioning research typically shows positive diversity- productivity relationships. However, local increases in species richness can increase competition within trophic levels, reducing the efficacy of intertrophic level population control. Pseudomonas spp. are a dominant group of soil bacteria that play key roles in plant growth promotion and control of crop fungal pathogens. Here we show that Pseudomonas spp. richness is positively correlated with take-all disease in wheat and with yield losses of ~3 t/ha in the field. We modeled the interactions between Pseudomonas and the take-all pathogen in abstract experimental microcosms, and show that increased bacterial genotypic richness escalates bacterial antagonism and decreases the ability of the bacterial community to inhibit growth of the take-all pathogen. Future work is required to determine the generality of these negative biodiversity effects on different media and directly at infection zones on root surfaces. However, the increase in competition between bacteria at high genotypic richness and the potential loss of fungal biocontrol activity highlights an important mechanism to explain the negative Pseudomonas diversity-wheat yield relationship we observed in the field. Together our results suggest that the effect of biodiversity on ecosystem functioning can depend on both the function and trophic level of interest. PMID- 27549740 TI - Food protein-based phytosterol nanoparticles: fabrication and characterization. AB - The development of food-grade (nano)particles as a delivery system for poorly water soluble bioactives has recently attracted increasing attention. This work is an attempt to fabricate food protein-based nanoparticles as delivery systems for improving the water dispersion and bioaccessibility of phytosterols (PS) by an emulsification-evaporation method. The fabricated PS nanoparticles were characterized in terms of particle size, encapsulation efficiency (EE%) and loading amount (LA), and xi-potential. Among all the test proteins, including soy protein isolate (SPI), whey protein concentrate (WPC) and sodium caseinate (SC), SC was confirmed to be the most suitable protein for the PS nano-formulation. Besides the type of protein, the particle size, EE% and LA of PS in the nanoparticles varied with the applied protein concentration in the aqueous phase and organic volume fraction. The freeze-dried PS nanoparticles with SC exhibited good water re-dispersion behavior and low crystallinity of PS. The LA of PS in the nanoparticles decreased upon storage, especially at high temperatures (e.g., >25 degrees C). The PS in the fabricated nanoparticles exhibited much better bioaccessibility than free PS. The findings would be of relevance for the fabrication of food-grade colloidal phytosterols, with great potential to be applied in functional food formulations. PMID- 27549741 TI - Clear cell adenocarcinoma of the cervix in a ten-year-old girl without prenatal diethylstilbestrol exposure. PMID- 27549743 TI - Corrigendum: The Cipher Code of Simple Sequence Repeats in "Vampire Pathogens". PMID- 27549744 TI - Garenoxacin pharmacokinetics in patients undergoing maintenance hemodialysis. AB - INTRODUCTION: Studies on the pharmacokinetics of the antibiotic garenoxacin (GRNX) in patients with renal insufficiency are lacking. In this study, we attempted to ascertain the appropriate dose of GRNX in patients undergoing maintenance hemodialysis (MH) based on pharmacokinetic parameters and clinical outcomes. METHODS: Six male patients with infections who were undergoing MH received 200 mg GRNX once daily. Blood samples were taken before and at 1, 2, 4, 6, 12, and 24 hours after GRNX administration. Plasma GRNX concentrations were measured using high-performance liquid chromatography. FINDINGS: The mean maximum plasma concentration (Cmax ) was 3.00 +/- 1.12 ug/mL, time to maximum plasma concentration (Tmax ) was 3.0 +/- 2.0 hours, and area under the curve for 24 hours (AUC0-24 ) was 40.7 +/- 16.7 ug.h/mL. The half-life (T1/2 ) of GRNX could not be calculated because plasma concentrations remained high 24 hours after administration. Cmax was strongly associated with the GRNX dose per kilogram body weight (r = 0.85, P = 0.03). Clinically, fever resolved within 3 days of GRNX administration and C-reactive protein levels returned to normal 14 days after administration. One patient experienced temporary increases in serum transaminase levels. DISCUSSION: MH patients receiving 200 mg GRNX once daily for infection showed a reduced Cmax but similar AUC0-24 compared with healthy individuals. While this study evaluated the effect of GRNX treatment, further research is needed to assess the accumulation of GRNX and the impact of continuous administration on its pharmacokinetics, as well as to prevent the development of resistant mutants. PMID- 27549742 TI - Topology and structure of an engineered human cohesin complex bound to Pds5B. AB - The cohesin subunits Smc1, Smc3 and Scc1 form large tripartite rings which mediate sister chromatid cohesion and chromatin structure. These are thought to entrap DNA with the help of the associated proteins SA1/2 and Pds5A/B. Structural information is available for parts of cohesin, but analyses of entire cohesin complexes are limited by their flexibility. Here we generated a more rigid 'bonsai' cohesin by truncating the coiled coils of Smc1 and Smc3 and used single particle electron microscopy, chemical crosslinking-mass spectrometry and in silico modelling to generate three-dimensional models of cohesin bound to Pds5B. The HEAT-repeat protein Pds5B forms a curved structure around the nucleotide binding domains of Smc1 and Smc3 and bridges the Smc3-Scc1 and SA1-Scc1 interfaces. These results indicate that Pds5B forms an integral part of the cohesin ring by contacting all other cohesin subunits, a property that may reflect the complex role of Pds5 proteins in controlling cohesin-DNA interactions. PMID- 27549745 TI - Mechanistic Insights into Ring Cleavage and Contraction of Benzene over a Titanium Hydride Cluster. AB - Carbon-carbon bond cleavage of benzene by transition metals is of great fundamental interest and practical importance, as this transformation is involved in the production of fuels and other important chemicals in the industrial hydrocracking of naphtha on solid catalysts. Although this transformation is thought to rely on cooperation of multiple metal sites, molecular-level information on the reaction mechanism has remained scarce to date. Here, we report the DFT studies of the ring cleavage and contraction of benzene by a molecular trinuclear titanium hydride cluster. Our studies suggest that the reaction is initiated by benzene coordination, followed by H2 release, C6H6 hydrometalation, repeated C-C and C-H bond cleavage and formation to give a MeC5H4 unit, and insertion of a Ti atom into the MeC5H4 unit with release of H2 to give a metallacycle product. The C-C bond cleavage and ring contraction of toluene can also occur in a similar fashion, though some details are different due to the presence of the methyl substituent. Obviously, the facile release of H2 from the metal hydride cluster to provide electrons and to alter the charge population at the metal centers, in combination with the flexible metal-hydride connections and dynamic redox behavior of the trimetallic framework, has enabled this unusual transformation to occur. This work has not only provided unprecedented insights into the activation and transformation of benzene over a multimetallic framework but it may also offer help in the design of new molecular catalysts for the activation and transformation of inactive aromatics. PMID- 27549746 TI - Prevalence and prognosis of hypoglycaemia in patients receiving maintenance dialysis. AB - BACKGROUND: End-stage renal disease is a common predisposing condition for the development of hypoglycaemia. AIM: To determine the effect of hypoglycaemia on the mortality of patients undergoing maintenance dialysis. METHODS: Retrospective and descriptive analyses were performed in five dialysis centres in the Republic of Korea between June 2002 and August 2008. We enrolled 1685 patients who had undergone dialysis for at least 1 month. RESULTS: We identified 453 episodes of hypoglycaemia in 256 of 1685 patients (15.2%); 189 patients (73.8%) had diabetes, whereas the other patients did not. The occurrence of hypoglycaemia in patients receiving dialysis appeared to be a life-threatening complication because 27.0% of patients died within two days of the onset of a hypoglycaemic episode. Older age, low serum albumin levels and infections were independent risk factors for total mortality in these patients. Furthermore, the absence of diabetes, age and serum glucose levels were independent factors associated with early mortality within two days of the development of hypoglycaemia. CONCLUSION: Although several factors were associated with mortality, the degree of hypoglycaemia, absence of diabetes and old age were associated with early mortality. Elderly hypoglycaemic patients, especially those without diabetes, should be closely monitored. PMID- 27549747 TI - Amplitude of accommodation in an 11- to 17-year-old Iranian population. AB - PURPOSE: The aim was to determine normal values of accommodative amplitude (AA) during adolescence in Iran. METHODS: In this cross-sectional study, sampling was done from high school students in Kermanshah in 2015 through a multi-stage cluster sampling method and selected students were invited to participate in the study. Examinations were performed on-site at each sampled high school. All students had visual acuity and refractive examination followed by measurement of AA. Accommodative amplitude was tested with Donder's push-up method using a Royal Air Force (RAF) near point rule. RESULTS: Of the 1,070 selected students, 901 were included in the study and their mean age was 14.4 +/- 1.7 years. Mean AA in this study was 11.53 +/- 3.02 D (range: 5.00-28.50 D). Mean AA was 15.33 D in 11 year-olds and significantly decreased with age, until it reached 10.40 D in the 17-year-old age group. Mean AA in boys and girls were 10.09 +/- 2.48 D and 11.65 +/- 3.03 D, respectively. Based on the multiple linear regression model, younger age (coefficient = -0.774) and female gender (coefficient = 1.060) significantly associated with AA. CONCLUSION: This study showed that the AA in Iranian teenagers is lower than that calculated with Hofstetter's formula. It is important to take account of this point when making diagnostic and therapeutic decisions. PMID- 27549748 TI - Structure and variation of the Fringillidae (Aves: Passeriformes) mitochondrial DNA control region and their phylogenetic relationship. AB - The control region is the major noncoding segment of animal mitochondrial DNA. To infer the structure and variation of Fringillidae mitochondrial DNA control region, the entire control region sequences of 25 species were analyzed. The length of the control region sequences was very conserved (1230 +/- 18) and can be separated into three domains. The frequency of both substitutions and gaps was highest in the third domain and lowest in the central region. The control region has the same flanking gene order from tRNAGlu to tRNAPhe. Genetic distances between species ranged from 1.80% (between Carduelis pinus and Carduelis spinus) to 25.34% (between Carduelis sinica and Coccothraustes vespertinus). The average genetic distances among the species within the genera varied from 5.11% (Leucosticte) to 14.31% (Carpodacus). The average genetic distances showed insignificantly negative correlation with ts/tv. Domain III is the most variable of the three domains among all the genera. The control region of Fringillidae contains a putative TAS element and the highly conserved CSB-1, and F, E, D, C boxes. However, neither CSB-2 nor CSB-3 could be unambiguously identified in the Fringillidae. The maximum likelihood method was used to construct a phylogenetic tree. Control region analysis demonstrated that some currently recognized genera may be polyphyletic, including Carpodacus, Carduelis and Serinus. PMID- 27549749 TI - Congenital bicuspid pulmonary valve. An uncommon impede for Ross procedure. AB - We report a case of successful heterograft aortic valve replacement following an impede Ross procedure in a 48-year-old man presenting with a congenital bicuspid pulmonary valve. The patient was admitted for aortic valve stenosis that required an aortic valve replacement (AVR). Owing to his young age and reluctance to long term anticoagulation therapy, it was decided to do an AVR by pulmonary autograft. During surgery, the anatomical unsuitability of the graft was discovered leading to the procedure's readjustment. PMID- 27549750 TI - Langmuir-Blodgett films of salophen-based metallosurfactants as surface pretreatment coatings for corrosion mitigation. AB - Salophen-based metallosurfactants are successfully used as pretreatment LB films for corrosion mitigation in acidic and saline media. Passivation of electron transfer is clearly demonstrated in gold electrodes, while 99.5% iron substrates treated with such films show up to an impressive 30% corrosion mitigation. PMID- 27549751 TI - Comparison of patient perceptions of Telehealth-supported and specialist nursing interventions for early stage COPD: a qualitative study. AB - BACKGROUND: The increasing prevalence and associated cost of treating Chronic Obstructive Pulmonary Disease (COPD) is unsustainable, and focus is needed on self-management and prevention of hospital admissions. Telehealth monitoring of patients' vital signs allows clinicians to prioritise their workload and enables patients to take more responsibility for their health. This paper reports the results of a qualitative study embedded within a feasibility and pilot Randomised Controlled Trial (RCT) of Telehealth-supported care within a community-based COPD supported-discharge service. The aim of the study was to qualitatively explore the experiences of patients with COPD who had received either a Telehealth supported or a specialist nursing intervention following their discharge from hospital after an admission for a COPD exacerbation. METHODS: Patients were invited to either participate in semi-structured interviews or to complete a semi structured self-administered questionnaire on completion of the intervention. Nine patients were interviewed (67 % female) and seventeen patients completed the questionnaires. In addition, three clinicians responsible for the delivery of both interventions were interviewed to obtain their perspectives on the new services. RESULTS: Seven underlying themes emerged from the patient interviews and were further explored in the questionnaires: (1) patient demographics; (2) information received by the participants; (3) installation of the Telehealth technology; (4) Telehealth service functionality; (5) visits; (6) service withdrawal; and (7) service perceptions. Recipients of both services reported feelings of safety derived from the delivery of an integrated, community-based service. CONCLUSIONS: Although recipients of the Telehealth service received 50 % fewer home visits from the clinicians than recipients of a more traditional community-based nursing intervention, the patients were enthusiastic about the service, with some describing it as the best service they had ever received. This suggests that a Telehealth intervention is an acceptable alternative to a more traditional home nursing visit model for monitoring community-based patients with COPD following their discharge from hospital. TRIAL REGISTRATION: Current Controlled Trials ISRCTN68856013. PMID- 27549752 TI - The expression patterns of aquaporin 9, vacuolar H+-ATPase, and cytokeratin 5 in the epididymis of the common vampire bat. AB - Desmodus rotundus is a vampire bat species that inhabits Latin America. Some basic aspects of this species' biology are still unknown, as the histophysiological characteristics of the male reproductive tract. Our study has focused on its epididymis, which is an important organ for performing a variety of functions, especially the sperm maturation and storage. The aim of this study was to identify principal, narrow, clear, and basal cells using cell-specific markers such as aquaporin 9 (AQP9), vacuolar H+-ATPase (V-ATPase), and cytokeratin 5 (KRT5). Principal cells were labeled by AQP9 from initial segment to cauda region in their stereocilia. They were shown with a columnar shape, whereas V-ATPase-rich cells were identified with a goblet-shaped body along the entire epididymis, including the initial segment, which were named as clear cells. Pencil-shaped V-ATPase-rich cells (narrow cells) were not detected in the initial segment of the bat epididymis, unlike in the rodent. Basal cells were labeled by KRT5 and were located at the basal portion of the epithelium forming a dense network. However, no basal cells with a luminal-reaching body extension were observed in the bat epididymis. In summary, epithelial cells were identified by their specific markers in the vampire bat epididymis. Principal and basal cells were labeled by AQP9 and KRT5, respectively. Narrow cells were not observed in the vampire bat epididymis, whereas clear cells were identified by V-ATPase labeling along the entire duct in a goblet-shaped body. In addition, no luminal reaching basal cells were observed in the vampire bat epididymis. PMID- 27549753 TI - Erythropoietin Treatment in Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - OBJECTIVE: Erythropoietin (EPO) for treating acute ischemic stroke (AIS) has been investigated in many studies. However, the evidence was inconsistent. Thus, a systematic review and metaanalysis were performed to elucidate the role of EPO in treating patients with AIS. METHODS: Two electronic databases (PubMed and EMBASE) were used. 30-day NIHSS measures primary outcome while all-cause mortality in the follow up and 90-day Barthel Index were regarded as secondary outcome. Results are presented as relative risk (RR), standardized mean difference (SMD) and 95% confidence intervals (CI). We employed Stata software to perform the meta analysis. RESULTS: Four randomized controlled trials (RCTs) involving 784 patients were contained in this metaanalysis. The total combined results on 30 day NIHSS were (SMD = -0.52, 95% CI: -1.39, 0.34) with random-effects model and sensitivity analysis showed a significant difference after excluding the Ehrenreich 2009 trial. The total combined secondary measured results were (RR=1.72, 95% CI: 1.10, 2.70) and (SMD = 0.01, 95% CI: -0.14, 0.16) for all-cause mortality and 90-day Barthel Index. In the subgroup analysis by using recombinant tissue plasminogen activator (rtPA) earlier, the rtPA group showed increased all cause mortality with the result of (RR = 1.92, 95% CI: 1.04, 3.52), but not in non-rtPA group. CONCLUSION: To our systematic review and meta-analysis, we didn't recommend EPO administration for patients with AIS, especially with the combination of rtPA. Large RCTs are warranted to examine EPO efficacy in AIS patients in the future. PMID- 27549754 TI - Eosinophils, probiotics, and the microbiome. AB - There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored. PMID- 27549756 TI - Protein Termini. AB - Since the first and the last residues of a protein have peculiar properties, unique amongst all residues, they have been analyzed repeatedly during the last decades. In this brief review, I try to summarize, besides the biochemical roles, the five features that have attracted most attention: (i) the Euclidean distance between the N- and C-termini and its relevance to protein folding, (ii) the reason why the termini are solvent exposed, (iii) the backbone conformation of the termini, (iv) the amino acid composition of the termini, and (v) the role of the termini in protein crystallization. Each of these five issues, which deserve attention nowadays thanks to the availability of massive amounts of data, is accompanied by my personal outlook of the research in the field. PMID- 27549755 TI - Prospective evaluation of an automated method to identify patients with severe sepsis or septic shock in the emergency department. AB - BACKGROUND: Sepsis is an often-fatal syndrome resulting from severe infection. Rapid identification and treatment are critical for septic patients. We therefore developed a probabilistic model to identify septic patients in the emergency department (ED). We aimed to produce a model that identifies 80 % of sepsis patients, with no more than 15 false positive alerts per day, within one hour of ED admission, using routine clinical data. METHODS: We developed the model using retrospective data for 132,748 ED encounters (549 septic), with manual chart review to confirm cases of severe sepsis or septic shock from January 2006 through December 2008. A naive Bayes model was used to select model features, starting with clinician-proposed candidate variables, which were then used to calculate the probability of sepsis. We evaluated the accuracy of the resulting model in 93,733 ED encounters from April 2009 through June 2010. RESULTS: The final model included mean blood pressure, temperature, age, heart rate, and white blood cell count. The area under the receiver operating characteristic curve (AUC) for the continuous predictor model was 0.953. The binary alert achieved 76.4 % sensitivity with a false positive rate of 4.7 %. CONCLUSIONS: We developed and validated a probabilistic model to identify sepsis early in an ED encounter. Despite changes in process, organizational focus, and the H1N1 influenza pandemic, our model performed adequately in our validation cohort, suggesting that it will be generalizable. PMID- 27549757 TI - Lesion of the rostromedial tegmental nucleus increases voluntary ethanol consumption and accelerates extinction of ethanol-induced conditioned taste aversion. AB - RATIONALE: Ethanol has rewarding and aversive properties, and the balance of these properties influences voluntary ethanol consumption. Preclinical and clinical evidence show that the aversive properties of ethanol limit intake. The neural circuits underlying ethanol-induced aversion learning are not fully understood. We have previously shown that the lateral habenula (LHb), a region critical for aversive conditioning, plays an important role in ethanol-directed behaviors. However, the neurocircuitry through which LHb exerts its actions is unknown. OBJECTIVE: In the present study, we investigate a role for the rostromedial tegmental nucleus (RMTg), a major LHb projection target, in regulating ethanol-directed behaviors. METHODS: Rats received either sham or RMTg lesions and were studied during voluntary ethanol consumption; operant ethanol self-administration, extinction, and yohimbine-induced reinstatement of ethanol seeking; and ethanol-induced conditioned taste aversion (CTA). RESULTS: RMTg lesions increased voluntary ethanol consumption and accelerated extinction of ethanol-induced CTA. CONCLUSIONS: The RMTg plays an important role in regulating voluntary ethanol consumption, possibly by mediating ethanol-induced aversive conditioning. PMID- 27549758 TI - Distinct neuronal patterns of positive and negative moral processing in psychopathy. AB - Psychopathy is a disorder characterized by severe and frequent moral violations in multiple domains of life. Numerous studies have shown psychopathy-related limbic brain abnormalities during moral processing; however, these studies only examined negatively valenced moral stimuli. Here, we aimed to replicate prior psychopathy research on negative moral judgments and to extend this work by examining psychopathy-related abnormalities in the processing of controversial moral stimuli and positive moral processing. Incarcerated adult males (N = 245) completed a functional magnetic resonance imaging protocol on a mobile imaging system stationed at the prison. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R). Participants were then shown words describing three types of moral stimuli: wrong (e.g., stealing), not wrong (e.g., charity), and controversial (e.g., euthanasia). Participants rated each stimulus as either wrong or not wrong. PCL-R total scores were correlated with not wrong behavioral responses to wrong moral stimuli, and were inversely related to hemodynamic activity in the anterior cingulate cortex in the contrast of wrong > not wrong. In the controversial > noncontroversial comparison, psychopathy was inversely associated with activity in the temporal parietal junction and dorsolateral prefrontal cortex. These results indicate that psychopathy-related abnormalities are observed during the processing of complex, negative, and positive moral stimuli. PMID- 27549759 TI - Phenotypic and metabolic features of mouse diaphragm and gastrocnemius muscles in chronic lung carcinogenesis: influence of underlying emphysema. AB - BACKGROUND: Muscle wasting negatively impacts the progress of chronic diseases such as lung cancer (LC) and emphysema, which are in turn interrelated. OBJECTIVES: We hypothesized that muscle atrophy and body weight loss may develop in an experimental mouse model of lung carcinogenesis, that the profile of alterations in muscle fiber phenotype (fiber type composition and morphometry, muscle structural alterations, and nuclear apoptosis), and in muscle metabolism are similar in both respiratory and limb muscles of the tumor-bearing mice, and that the presence of underlying emphysema may influence those events. METHODS: Diaphragm and gastrocnemius muscles of mice with urethane-induced lung cancer (LC U) with and without elastase-induced emphysema (E-U) and non-exposed controls (N = 8/group) were studied: fiber type composition, morphometry, muscle abnormalities, apoptotic nuclei (immunohistochemistry), and proteolytic and autophagy markers (immunoblotting) at 20- and 35-week exposure times. In the latter cohort, structural contractile proteins, creatine kinase (CK), peroxisome proliferator-activated receptor (PPAR) expression, oxidative stress, and inflammation were also measured. Body and muscle weights were quantified (baseline, during follow-up, and sacrifice). RESULTS: Compared to controls, in U and E-U mice, whole body, diaphragm and gastrocnemius weights were reduced. Additionally, both in diaphragm and gastrocnemius, muscle fiber cross-sectional areas were smaller, structural abnormalities, autophagy and apoptotic nuclei were increased, while levels of actin, myosin, CK, PPARs, and antioxidants were decreased, and muscle proteolytic markers did not vary among groups. CONCLUSIONS: In this model of lung carcinogenesis with and without emphysema, reduced body weight gain and muscle atrophy were observed in respiratory and limb muscles of mice after 20- and 35-week exposure times most likely through increased nuclear apoptosis and autophagy. Underlying emphysema induced a larger reduction in the size of slow- and fast-twitch fibers in the diaphragm of U and E-U mice probably as a result of the greater inspiratory burden imposed onto this muscle. PMID- 27549760 TI - Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis. AB - PURPOSE: The purpose of this study was to evaluate the best protocol to prepare endometrium for frozen embryo replacement (FER) cycles. METHODS: This study is a systematic review and meta-analysis. Following PubMed and OvidSP search, a total of 1166 studies published after 1990 were identified following removal of duplicates. Following exclusion of studies not matching our inclusion criteria, a total of 33 studies were analyzed. Primary outcome measure was live birth. The following protocols, including true natural cycle (tNC), modified natural cycle (mNC), artificial cycle (AC) with or without suppression, and mild ovarian stimulation (OS) with gonadotropin (Gn) or aromatase inhibitor (AI), were compared. RESULTS: No statistically significant difference for both clinical pregnancy and live birth was noted between tNC and mNC groups. When tNC and AC without suppression groups are compared, there was a statistically significant difference in clinical pregnancy rate in favor of tNC, whereas it failed to reach statistical significance for live birth. When tNC and AC with suppression groups are compared, there was a statistically significant difference in live birth rate favoring the latter. Similar pregnancy outcome was noted among mNC versus AC with or without suppression groups. Similarly, no difference in clinical pregnancy and live birth was noted when ACs with or without suppression groups are compared. CONCLUSIONS: There is no consistent superiority of any endometrial preparation for FER. However, mNC has several advantages (being patient-friendly; yielding at least equivalent or better pregnancy rates when compared with tNC and AC with or without suppression; may not require LPS). Mild OS with Gn or AI may be promising. PMID- 27549761 TI - A predictive bone drilling force model for haptic rendering with experimental validation using fresh cadaveric bone. AB - PURPOSE: Bone drilling simulators with virtual and haptic feedback provide a safe, cost-effective and repeatable alternative to traditional surgical training methods. To develop such a simulator, accurate haptic rendering based on a force model is required to feedback bone drilling forces based on user input. Current predictive bone drilling force models based on bovine bones with various drilling conditions and parameters are not representative of the bone drilling process in bone surgery. The objective of this study was to provide a bone drilling force model for haptic rendering based on calibration and validation experiments in fresh cadaveric bones with different bone densities. METHODS: Using a commonly used drill bit geometry (2 mm diameter), feed rates (20-60 mm/min) and spindle speeds (4000-6000 rpm) in orthognathic surgeries, the bone drilling forces of specimens from two groups were measured and the calibration coefficients of the specific normal and frictional pressures were determined. RESULTS: The comparison of the predicted forces and the measured forces from validation experiments with a large range of feed rates and spindle speeds demonstrates that the proposed bone drilling forces can predict the trends and average forces well. CONCLUSION: The presented bone drilling force model can be used for haptic rendering in surgical simulators. PMID- 27549763 TI - Disease modifying therapies for relapsing multiple sclerosis. AB - Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed. PMID- 27549762 TI - The role of cell location and spatial gradients in the evolutionary dynamics of colon and intestinal crypts. AB - BACKGROUND: Colon and intestinal crypts serve as an important model system for adult stem cell proliferation and differentiation. We develop a spatial stochastic model to study the rate of somatic evolution in a normal crypt, focusing on the production of two-hit mutants that inactivate a tumor suppressor gene. We investigate the effect of cell division pattern along the crypt on mutant production, assuming that the division rate of each cell depends on its location. RESULTS: We find that higher probability of division at the bottom of the crypt, where the stem cells are located, leads to a higher rate of double-hit mutant production. The optimal case for delaying mutations occurs when most of the cell divisions happen at the top of the crypt. We further consider an optimization problem where the "evolutionary" penalty for double-hit mutant generation is complemented with a "functional" penalty that assures that fully differentiated cells at the top of the crypt cannot divide. CONCLUSION: The trade off between the two types of objectives leads to the selection of an intermediate division pattern, where the cells in the middle of the crypt divide with the highest rate. This matches the pattern of cell divisions obtained experimentally in murine crypts. REVIEWERS: This article was reviewed by David Axelrod (nominated by an Editorial Board member, Marek Kimmel), Yang Kuang and Anna Marciniak-Czochra. For the full reviews, please go to the Reviewers' comments section. PMID- 27549764 TI - Homeostatic dynamics, hysteresis and synchronization in a low-dimensional model of burst suppression. AB - Burst suppression, a pattern of the electroencephalogram characterized by quasi periodic alternation of high-voltage activity (burst) and isoelectric silence (suppression), is typically associated with states of unconsciousness, such as in deep general anesthesia and certain etiologies of coma. Recent computational models for burst suppression have attributed the slow (up to tens of seconds) time-scale of burst termination and re-initiation to cycling in supportive physiological process, such as cerebral metabolism. That is, activity-dependent substrate ('energy') depletion during bursts, followed by substrate recovery during suppression. Such a model falls into the category of a fast-slow dynamical system, commonly used to describe neuronal bursting more generally. Here, following this basic paradigm, we develop a low dimensional mean field model for burst suppression that adds several new features and capabilities to previous models. Most notably, this new model includes explicit homeostatic interactions wherein the rates of substrate recovery are tied to neuronal activity in a supply demand loop, creating a physiologically consistent, reciprocal interaction between the neural and substrate processes. We develop formal analysis of the model dynamics, showing, in particular, the capability of the model to produce burst-like activity as a consequence of neuronal downregulation only, without any direct perturbation to the substrate dynamics. Further, we use a synchronization analysis to contrast different mechanisms for spatially local versus global bursting. The analysis performed generates characterizations that are consistent with experimental observations of spatiotemporal features such as burst onset, duration, and spatial organization and, moreover, generates predictions regarding the presence of bistability and hysteresis in the underlying system. Thus, the model provides new dynamical insight into the mechanisms of burst suppression and, moreover, a tractable platform for more detailed future characterizations. PMID- 27549765 TI - Metabolomic biosignature differentiates melancholic depressive patients from healthy controls. AB - BACKGROUND: Major depressive disorder (MDD) is a heterogeneous disease at the level of clinical symptoms, and this heterogeneity is likely reflected at the level of biology. Two clinical subtypes within MDD that have garnered interest are "melancholic depression" and "anxious depression". Metabolomics enables us to characterize hundreds of small molecules that comprise the metabolome, and recent work suggests the blood metabolome may be able to inform treatment decisions for MDD, however work is at an early stage. Here we examine a metabolomics data set to (1) test whether clinically homogenous MDD subtypes are also more biologically homogeneous, and hence more predictiable, (2) devise a robust machine learning framework that preserves biological meaning, and (3) describe the metabolomic biosignature for melancholic depression. RESULTS: With the proposed computational system we achieves around 80 % classification accuracy, sensitivity and specificity for melancholic depression, but only ~72 % for anxious depression or MDD, suggesting the blood metabolome contains more information about melancholic depression.. We develop an ensemble feature selection framework (EFSF) in which features are first clustered, and learning then takes place on the cluster centroids, retaining information about correlated features during the feature selection process rather than discarding them as most machine learning methods will do. Analysis of the most discriminative feature clusters revealed differences in metabolic classes such as amino acids and lipids as well as pathways studied extensively in MDD such as the activation of cortisol in chronic stress. CONCLUSIONS: We find the greater clinical homogeneity does indeed lead to better prediction based on biological measurements in the case of melancholic depression. Melancholic depression is shown to be associated with changes in amino acids, catecholamines, lipids, stress hormones, and immune-related metabolites. The proposed computational framework can be adapted to analyze data from many other biomedical applications where the data has similar characteristics. PMID- 27549766 TI - Age-related differences in ocular biometry in adult Korean population. AB - BACKGROUND: To evaluate the relationship between age, axial length (AL), anterior chamber depth (ACD) and corneal steepness (K) in patients with cataract. METHODS: In this retrospective study, medical records of 800 patients (800 eyes) who were diagnosed with cataract and received preoperative ophthalmologic examination were reviewed. Data including age, gender and ocular biometric data including AL, ACD and K were collected and analyzed using univariate and multivariate analyses. RESULTS: Univariate analysis showed increased age has significant correlation with shorter AL (P < 0.001), shallower ACD (P < 0.001) and steeper K (P < 0.001). K value has a negative correlation with AL (P < 0.001). In multivariate analysis, increasing age has a significant association with shorter AL (P < 0.001) and ACD (P < 0.001), although the association between age and K was not significant (P = 0.398). Negative correlation between AL and K remained significant in multivariate analysis (P < 0.001). CONCLUSION: In patients with cataract, older age had significant association with shorter AL and ACD. AL and K had negative correlation. PMID- 27549767 TI - Conservation in the phylum of the local homology of apolipoproteins with the thyroid hormone plasma carriers. AB - Thyroxine-binding globulin (TBG), transthyretin (TTR), albumin (HSA), plus other plasmatic proteins, which include apolipoproteins, can bind and transport thyroid hormones (TH). In 1994, a 5-residue motif (Y, L/I/M, X, X, V/L/I) conserved in human TBG, TTR, HSA, and human and animal apolipoproteins was identified. Recently, we noticed that a number of residues upstream and downstream that motif are also conserved.We tested in silico the conservation of this larger motif in the many additional animal sequences of TH plasma carriers discovered after 1994. To this aim, we searched for the occurrence of the "new" motif in human and animal apolipoprotein and non-apolipoprotein TH-binding plasmatic proteins, and in a group of randomly selected proteins (2918 sequences from 56 species) not known as TH binders.Our results confirm the conservation of the "new" motif, associated with TH binding, in a total of 426 sequences analyzed (220 belonging to 169 apolipoproteins from 69 species, 206 belonging to 123 nonapolipoproteins from 54 species). Additionally, we found that within such conserved segments some differences between groups of TH plasma carriers exist. Interestingly, number and type of differences appear related to the affinity of each carrier for thyroid hormones. No occurrence of the motif was found in control proteins (alpha- and beta-tubulin, eosinophil cationic protein, endothelin-1, -2 and -3, IgG receptor, tropomyosin, Wnt inhibitory factor 1, erythropoietin, insulin and haptoglobin).Maintenance of a TH-binding domain in apolipoproteins throughout the phylum should be not less important that maintenance of the lipid binding domain. PMID- 27549768 TI - Management of Narcolepsy. AB - OPINION STATEMENT: Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms. We recommend that medications and guidelines in NT2 should be the same as for NT1 (except for cataplexy), but the benefit risk ratio should be reassessed regularly. The main symptom in both diseases is a disabling excessive daytime sleepiness (EDS). First-line medications should be stimulants such as modafinil, armodafinil, or sodium oxybate, second-line methylphenidate and pitolisant, where available, and amphetamines as third-line therapy. Sodium oxybate has the advantage to be also effective to manage the fragmented nocturnal sleep, another common symptom in NT1. We advise to wait a few weeks with a stimulant drug before starting an anticataplectic treatment in NT1, except for severe cataplexy. Furthermore, cataplexy treatment should not be systematic. First-line strategy is the use of sodium oxybate, the only drug approved for cataplexy and EDS in adults. However, antidepressant agents such as venlafaxine are also commonly used, with few adverse effects and a good efficacy, although based on expert consensus only. A clinically relevant tool is required to quantify the severity of narcolepsy, subjective symptoms, and their consequences, to monitor the treatment efficacy, and to finally optimize narcolepsy management. In the future, Hcrt replacement or Hcrt agonists will certainly be options to treat NT1, but for now the different peptides do not cross easily the blood brain barrier. Immune-based therapies are other possibilities in NT1, at disease onset, with already some successful attempts to slow down or stop the autoimmune process. PMID- 27549769 TI - Bo-Gan-Whan regulates proliferation and migration of vascular smooth muscle cells. AB - BACKGROUND: Bo-Gan-Whan (BGH), a Korean polyherbal medicine, is used as a hepatoprotective drug. It has six natural sources, and has been demonstrated to have anti-oxidative, anti-cancer, and anti-inflammatory properties; however, its effect on vascular diseases remains unclear. METHODS: Cell viability and proliferation assays were employed using an EZ-Cytox Cell Viability Assay Kit. Platelet-derived growth factor (PDGF)-BB-induced vascular smooth muscle cell (VSMC) migration was measured by scratch wound healing assay and Boyden chamber assay. The expression levels of the phosphorylated signaling proteins relevant to proliferation, including extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) were determined by western blot analysis. Chromatogram and mass analysis were employed by Ultra Performance Liquid Chromatography (UPLC) system. Cell prolife ration and migration were also explored using the PDGF-BB-induced aortic sprout assay. RESULTS: BGH (100-500 MUg/mL) significantly inhibited the proliferation and migration of PDGF-BB stimulated VSMCs through the reduced phosphorylation of ERK1/2 and p38 MAPK in comparison to untreated PDGF-BB-stimulated VSMC. Moreover, we identified the paeoniflorin as the major composition of BGH. CONCLUSIONS: We suggest that BGH may have an anti-atherosclerosis effect by inhibiting the proliferation and migration of PDGF-BB-stimulated VSMCs through down-regulation of ERK1/2 and p38 MAPK phosphorylation. PMID- 27549770 TI - Chromosomer: a reference-based genome arrangement tool for producing draft chromosome sequences. AB - BACKGROUND: As the number of sequenced genomes rapidly increases, chromosome assembly is becoming an even more crucial step of any genome study. Since de novo chromosome assemblies are confounded by repeat-mediated artifacts, reference assisted assemblies that use comparative inference have become widely used, prompting the development of several reference-assisted assembly programs for prokaryotic and eukaryotic genomes. FINDINGS: We developed Chromosomer - a reference-based genome arrangement tool, which rapidly builds chromosomes from genome contigs or scaffolds using their alignments to a reference genome of a closely related species. Chromosomer does not require mate-pair libraries and it offers a number of auxiliary tools that implement common operations accompanying the genome assembly process. CONCLUSIONS: Despite implementing a straightforward alignment-based approach, Chromosomer is a useful tool for genomic analysis of species without chromosome maps. Putative chromosome assemblies by Chromosomer can be used in comparative genomic analysis, genomic variation assessment, potential linkage group inference and other kinds of analysis involving contig or scaffold mapping to a high-quality assembly. PMID- 27549772 TI - Palliative surgery for colorectal cancer with peritoneal metastasis: a propensity score matching analysis. AB - PURPOSE: Peritoneal metastasis (PM) in patients with colorectal cancer (CRC) is associated with poor prognosis. We conducted this study to assess whether palliative resection (PR) of the primary tumor improved the overall survival (OS) of patients with PM-CRC. METHODS: We analyzed retrospectively, data collected prospectively from patients with CRC. PM was categorized into three subgroups according to the Japanese classification of PM. A propensity-score model was used to compare the outcomes of patients who underwent PR (PR group) and those who did not [non-resection (NR) group]. RESULTS: Among 1909 patients with metastatic CRC, 309 (16 %) had only peritoneal metastases and 255 of these patients who underwent palliative surgery (R2) were the subjects of our analysis: 161 in the PR group and 94 in the NR group. Median OS was significantly longer in the PR group than in the NR group (23 vs. 11 months, P < 0.001). Patients in the PR group had less extensive PM and a higher rate of receiving palliative chemotherapy than those in the NR group (P < 0.001). In a Cox multivariate analysis of 69 propensity-score matched pairs, PR resulted in significantly longer OS than NR (hazard ratio 0.496, 95 % confidence interval 0.268-0.919, P = 0.025). CONCLUSIONS: Our results show that PR resulted in better OS than NR for patients with PM-CRC, when their overall condition permitted a more aggressive approach. PMID- 27549771 TI - Endometriosis and mammographic density measurements in the Nurses' Health Study II. AB - PURPOSE: Endometriosis and mammographic density have been hypothesized to be influenced by sex steroid hormonal exposures in adolescence and early adulthood. We investigated the association between endometriosis and mammographic density, a consistent and independent risk factor for breast cancer. METHODS: We conducted a cross-sectional analysis among 1,581 pre- and postmenopausal women not previously diagnosed with breast cancer in the Nurses' Health Study II cohort. We measured average percent mammographic density and absolute dense and non-dense breast area using a validated computer-assisted method. Multivariable linear regression was used to estimate the association between endometriosis and mammographic density among pre- and postmenopausal women separately. RESULTS: Among premenopausal women, average percent mammographic density was 43.1 % among women with endometriosis (n = 91) and 40.5 % among women without endometriosis (n = 1,150). Endometriosis was not associated significantly with mammographic density among premenopausal (% difference = 2.00 percentage points 95 % CI -1.33, 5.33) or among postmenopausal women (% difference = -0.89 percentage points 95 % CI -5.10, 3.33). Among premenopausal women, there was heterogeneity by BMI at age 18 (p value = 0.003), with a suggested association among those who were lean at age 18 (BMI < 20.6 kg/m(2)) (% difference = 3.74 percentage points 95 % CI -0.29, 7.78). CONCLUSION: Endometriosis was not found to be associated with overall measurements of mammographic density. PMID- 27549773 TI - Laparoscopic proximal gastrectomy for early gastric cancer. AB - The incidence of proximal early gastric cancer (EGC) is increasing, and while laparoscopic proximal gastrectomy (LPG) has been performed as a surgical option, it is not yet the standard treatment, because there is no established common reconstruction method following proximal gastrectomy (PG). We reviewed the English-language literature to clarify the current status and problems associated with LPG in treating proximal EGC. This procedure is considered indicated for EGC located in the upper third of the stomach with clinical T1N0, but not when it can be treated endoscopically. No operative mortality or conversion to open surgery was reported in our review, suggesting that this procedure is technically feasible. The most frequent postoperative complication involved problems with anastomoses, possibly caused by the technical complexity of the reconstruction. Although various reconstruction methods following open PG (OPG) and LPG have been reported, there is no standard reconstruction method. Well-designed multicenter, randomized, controlled, prospective trials to evaluate the various reconstruction methods are necessary. PMID- 27549774 TI - Treatment of tailgut cysts by extended distal rectal segmental resection with rectoanal anastomosis. AB - PURPOSE: Complete surgical resection is the treatment of choice for tailgut cysts, because of their malignant potential and tendency to regrow if incompletely resected. We report our experience of treating patients with tailgut cysts, and discuss diagnostics, surgical approaches, and follow-up. METHODS: We performed extended distal rectal segmental resection of the tailgut cyst, with rectoanal anastomosis. We report the clinical, radiological, pathological, and surgical findings, describe the procedures performed, and summarize follow-up data. RESULTS: Two patients underwent en-bloc resection of a tailgut cyst, the adjacent part of the levator muscle, and the distal rectal segment, followed by an end-to-end rectoanal anastomosis. There was no evidence of anastomotic leakage postoperatively. At the time of writing, our patients were relapse-free with no, or non-limiting, symptoms of anal incontinence, respectively. CONCLUSIONS: This surgical approach appears to have a low complication rate and good recovery outcomes. Moreover, as the sphincter is preserved, so is the postoperative anorectal function. This approach could result in a low recurrence rate. PMID- 27549775 TI - Necessity for autologous blood storage and transfusion in patients undergoing pancreatoduodenectomy. AB - PURPOSE: To establish which patients undergoing pancreaticoduodenectomy (PD) need autologous blood storage and transfusion. METHODS: Autologous blood was collected and stored for 69 patients scheduled to undergo PD, and not used in 50 patients. Based on the use of the deposited autologous blood and the estimated postoperative hemoglobin (Hb) level when blood was not deposited, we divided the patients into a "transfusion necessary" group and a "transfusion unnecessary" group. By comparing the two groups, we proposed a method of scoring to predict the necessity for storing autologous blood. RESULTS: The "transfusion necessary" group comprised 6 patients (2 who received homologous blood transfusion and 4 with an estimated postoperative Hb of <8.0 g/dL) and the "transfusion unnecessary" group comprised 63 patients (24 whose autologous blood was discarded and 39 with an estimated Hb >=8.0 g/dL). By analyzing the differences between the groups, including the preoperative hemoglobin level and the need for portal vein resection, we devised a scoring system to predict the necessity of collecting autologous blood. The scoring significantly correlated with the proportion of patients who did not require autologous blood storage and transfusion. CONCLUSIONS: Not all patients benefited from autologous blood storage and transfusion. Our scoring system proved useful for identifying which patients required autologous blood storage and transfusion during PD. PMID- 27549776 TI - Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma. AB - PURPOSES: We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. METHODS: The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n = 51), single- (n = 69), double- (n = 31), and triple-positive (n = 9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. RESULTS: The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11 % (P = 0.02), and 94, 88, 67, and 37 % (P < 0.001), respectively. The 2-year local recurrence rates were 6.5, 0, 41.2, and 61.9 %, respectively (P < 0.001). Multivariate analysis revealed that a double- or triple-positive pre-treatment tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95 % confidence interval (CI) 2.44-12.33, P < 0.001] and overall survival (HR 4.21, 95 % CI 1.89-9.37, P < 0.001). CONCLUSION: RFA may not be suitable for patients with HCC who have pre-treatment expression of >=two of these tumor markers. PMID- 27549777 TI - High serum levels of interleukin-6 in patients with advanced or metastatic colorectal cancer: the effect on the outcome and the response to chemotherapy plus bevacizumab. AB - PURPOSE: We evaluated the relationship of the pretreatment serum IL-6 levels with the outcome and treatment response in patients with advanced or metastatic colorectal cancer (CRC) who underwent bevacizumab-containing chemotherapy. METHODS: In this retrospective study, the pretreatment serum IL-6 and plasma vascular endothelial growth factor (VEGF) levels were measured in 113 patients with metastatic CRC. The cut-off values for these measurements, as determined by a receiver operating characteristic curve analysis, were 4.3 and 66 pg/mL, respectively. The median follow-up period was 19 months (range 1-40 months). Sixty-three patients had primary cancer, and 38 had a metachronous recurrence. Thirty patients underwent curative resection, and 71 underwent chemotherapy, 53 of whom received bevacizumab-containing chemotherapy. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier and multivariate Cox proportional hazards regression analyses. RESULTS: The plasma VEGF levels and positive KRAS mutation status were not associated with the outcomes. However, high serum IL-6 levels were significantly associated with poorer OS and PFS in comparison to low serum IL-6 levels. A Cox proportional hazards regression analysis showed that high serum IL-6 levels were an independent risk factor for a poor outcome. CONCLUSION: In patients with metastatic CRC, high pretreatment serum IL-6 levels were associated with a poor outcome and bevacizumab resistance. PMID- 27549779 TI - Adult ADHD Self-Report Scale: Comprehensive Psychometric Study in a Spanish SUD Sample. AB - OBJECTIVE: The purpose of this study is to provide reliability and validity evidence of the Adult Self-Report Scale (ASRS) scores on different versions and scoring procedures in a Spanish substance use disorder (SUD) sample. METHOD: The sample was made up of 170 outpatients diagnosed with SUD. The ASRS, the Mini International Neuropsychiatric Interview (MINI), and the Substance Dependence Severity Scale were administered. RESULTS: The results of the confirmatory factor analysis (CFA) showed adequate fit to the structure proposed by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) in the 18-item version. On the screening scale, best fit was found for a model with two correlated factors (inattention and hyperactivity). The exploratory factor analysis (EFA) showed that the ADHD items converge and are differentiated from symptoms of withdrawal. The regression analyses showed that severity of dependence is explained by the ASRS scores. CONCLUSION: Both versions of the ASRS showed adequate psychometric properties. The polytomous or dichotomous score is relevant in patient classification. PMID- 27549780 TI - Gender Differences in the Relationship Between Changes in ADHD Symptoms, Executive Functions, and Self- and Parent-Report Depression Symptoms in Boys and Girls With ADHD: A 2-Year Follow-Up Study. AB - OBJECTIVE: This study was conducted to investigate the association between changes in ADHD symptoms, executive functions (EFs), and depression symptoms in girls and boys with ADHD over a 2-year period. METHOD: Thirty-six girls and 39 boys with ADHD, 18 typically developing (TD) girls and 29 TD boys (ages 9-16) were included. Assessments of EFs, ADHD symptoms, and self- and parent-report of depression symptoms were carried out. RESULTS: For girls, a reduction of inattention symptoms was associated with a decline in parent-rated depression symptoms. A reduction in hyperactivity/impulsivity was associated with a reduction in self-rated depression symptoms in boys, and an increase in girls. A reduction in inattention symptoms was associated with a modest increase in self rated depression symptoms in both boys and girls. CONCLUSION: Gathering information from both the parents and the child with ADHD is important in determining how gender may be influencing symptom profiles. PMID- 27549778 TI - Investigation of mechanisms of bendiocarb resistance in Anopheles gambiae populations from the city of Yaounde, Cameroon. AB - BACKGROUND: Resistance to the carbamate insecticide bendiocarb is emerging in Anopheles gambiae populations from the city of Yaounde in Cameroon. However, the molecular basis of this resistance remains uncharacterized. The present study objective is to investigate mechanisms promoting resistance to bendiocarb in An. gambiae populations from Yaounde. METHODS: The level of susceptibility of An. gambiae s.l. to bendiocarb 0.1 % was assessed from 2010 to 2013 using bioassays. Mosquitoes resistant to bendiocarb, unexposed and susceptible mosquitoes were screened for the presence of the Ace-1(R) mutation using TaqMan assays. Microarray analyses were performed to assess the pattern of genes differentially expressed between resistant, unexposed and susceptible. RESULTS: Bendiocarb resistance was more prevalent in mosquitoes originating from cultivated sites compared to those from polluted and unpolluted sites. Both An. gambiae and Anopheles coluzzii were found to display resistance to bendiocarb. No G119S mutation was detected suggesting that resistance was mainly metabolic. Microarray analysis revealed the over-expression of several cytochrome P450 s genes including cyp6z3, cyp6z1, cyp12f2, cyp6m3 and cyp6p4. Gene ontology (GO) enrichment analysis supported the detoxification role of cytochrome P450 s with several GO terms associated with P450 activity significantly enriched in resistant samples. Other detoxification genes included UDP-glucosyl transferases, glutathione-S transferases and ABC transporters. CONCLUSION: The study highlights the probable implication of metabolic mechanisms in bendiocarb resistance in An. gambiae populations from Yaounde and stresses the need for further studies leading to functional validation of detoxification genes involved in this resistance. PMID- 27549781 TI - Demographic Differences in Disruptive Mood Dysregulation Disorder Symptoms in ADHD, Autism, and General Population Samples. AB - OBJECTIVE: Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) disruptive mood dysregulation disorder (DMDD) is a controversial new diagnosis. No studies have investigated DMDD symptoms (irritable-angry mood and temper outbursts) and demographics in general population and psychiatric samples. METHOD: Maternal ratings of DMDD symptoms and diagnoses, age, gender, IQ, race, and parent occupation were analyzed in general population (n = 665, 6-12 years) and psychiatric samples (n = 2,256, 2-16 years). RESULTS: Percentage of school age children with DMDD symptoms were 9% general population, 12% ADHD-I, 39% ADHD C, and 43% autism. Male, nonprofessional parent, and autism with IQ > 80 were associated with increasing DMDD symptoms, but demographics together explained only 2% to 3% of the DMDD score variance. CONCLUSION: Demographics contributed little to the presence of DMDD symptoms in all groups, whereas oppositional defiant disorder (ODD) explained most of the variance. Almost all children with DMDD symptoms had ODD suggesting that DMDD may not be distinct from ODD. PMID- 27549782 TI - Long-term integrated telerehabilitation of COPD Patients: a multicentre randomised controlled trial (iTrain). AB - BACKGROUND: Pulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic obstructive pulmonary disease (COPD). However, available resources are often limited, and many patients bear with poor availability of programmes. Sustaining PR benefits and regular exercise over the long term is difficult without any exercise maintenance strategy. In contrast to traditional centre-based PR programmes, telerehabilitation may promote more effective integration of exercise routines into daily life over the longer term and broaden its applicability and availability. A few studies showed promising results for telerehabilitation, but mostly with short-term interventions. The aim of this study is to compare long-term telerehabilitation with unsupervised exercise training at home and with standard care. METHODS/DESIGN: An international multicentre randomised controlled trial conducted across sites in three countries will recruit 120 patients with COPD. Participants will be randomly assigned to telerehabilitation, treadmill and control, and followed up for 2 years. The telerehabilitation intervention consists of individualised exercise training at home on a treadmill, telemonitoring by a physiotherapist via videoconferencing using a tablet computer, and self-management via a customised website. Patients in the treadmill arm are provided with a treadmill only to perform unsupervised exercise training at home. Patients in the control arm are offered standard care. The primary outcome is the combined number of hospitalisations and emergency department presentations. Secondary outcomes include changes in health status, quality of life, anxiety and depression, self efficacy, subjective impression of change, physical performance, level of physical activity, and personal experiences in telerehabilitation. DISCUSSION: This trial will provide evidence on whether long-term telerehabilitation represents a cost-effective strategy for the follow-up of patients with COPD. The delivery of telerehabilitation services will also broaden the availability of PR and maintenance strategies, especially to those living in remote areas and with no access to centre-based exercise programmes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02258646 . PMID- 27549783 TI - Ultrastructural and molecular characterization of diversity among small araphid diatoms all lacking rimoportulae. I. Five new genera, eight new species. AB - Pennate diatoms are important contributors to primary production in freshwater and marine habitats. But the extent of their diversity, ecology, and evolution is still largely unknown. This is particularly evident among the clades of pennate diatoms without raphe slits, whose diversity is likely underestimated due to their small size and features that can be difficult to discern under light microscopy. In this study, we described five new araphid genera with eight new species based on morphological observations (light and electron microscopy) and molecular data (nuclear-encoded small subunit ribosomal RNA and chloroplast encoded rbcL and psbC): Serratifera varisterna, Hendeyella rhombica, H. dimeregrammopsis, H. lineata, Psammotaenia lanceolata, Castoridens striata, C. hyalina, and Cratericulifera shandongensis. We also transferred Dimeregramma dubium to Hendeyella dubia. Phylogenetic analysis of the molecular data revealed that all the newly established taxa fell into a monophyletic group, with Fragilariforma virescens located at the base. The group was composed by two subclades: one comprising Castoridens, Cratericulifera, and Plagiostriata, and the larger including also the rest of the new genera plus some of the smallest known diatoms, such as Nanofrustulum, Opephora, Pseudostaurosira, Staurosirella, and Staurosira with a high level of support. This study enhances the general knowledge on the phylogeny and biodiversity of a group of small araphid diatoms that have been generally poorly described both by electron microscopy and DNA sequence data. PMID- 27549784 TI - One-step nucleic acid amplification (OSNA): where do we go with it? AB - The one-step nucleic acid amplification (OSNA) assay was initially developed for the intraoperative assessment of sentinel lymph node metastases in breast cancer. This assay measures cytokeratin 19 (CK19) mRNA copy number and is widely used in hospitals. The results of the IBCSG 23-01, ACOSOG Z0011, and AMAROS trials demonstrated that no further axillary dissection is required for patients with sentinel lymph nodes that tested positive for cancer, which has led to a decreasing trend in the need for intraoperative assessment of lymph nodes. Here, I review studies relevant to OSNA and discuss perspectives on future applications of OSNA in cancer surgery. The studies reviewed were identified by carrying out a search on PubMed for all articles pertaining to OSNA and published prior to the end of June 2016 using the keywords "OSNA" or "one-step nucleic acid amplification" in the title or abstract. Method comparison studies between OSNA and pathological assessment for the detection of lymph node metastasis in breast cancer revealed that in a pooled assessment OSNA had a high specificity (94.8 %), high concordant rate (93.8 %), and a negative predictive value (97.6 %). Similar results have been found for gastric, colorectal, and lung cancers in multicenter studies. These results demonstrate that OSNA can serve as an alternative method to pathological assessment for examining lymph node metastasis. Multicenter prospective studies with a large sample size are needed to definitively reveal the superiority of OSNA over pathological assessment to predict prognosis. Technical refinements to improve the assay are essential to its further development as a new standard for testing in place of pathological examination. PMID- 27549785 TI - Effect of the timing of best tumor shrinkage on survival of patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitor therapy. AB - BACKGROUND: To evaluate the association between the timing of best tumor shrinkage (bTS) and metastatic renal cell carcinoma (mRCC) patient survival after first-line tyrosine kinase inhibitor (TKI) therapy. METHODS: The tumors of 91 patients with mRCC showed a response to TKIs. None of the patients had received prior cytokine therapy. The magnitude of bTS was categorized according to the Response Evaluation Criteria in Solid Tumors v. 1.1. The patients were divided into two subgroups according to the timing of bTS: early responders (<=3 months) and late responders (>3 months). Overall survival (OS) and progression-free survival (PFS) after first-line TKI therapy were evaluated, and factors predicting survival were examined. RESULTS: Sunitinib, sorafenib, and pazopanib were used in 62, 25, and 4 responders, respectively. In total, 52 (57.1 %) and 39 (42.9 %) patients were early and late responders, respectively. Early responders had significantly lower PFS compared to late responders (median survival, 11.4 vs. 19.1 months; log-rank test, p = 0.0263), although there were no significant differences in the OS of early and late responders (27.0 vs. 30.1 months, p = 0.306). Multivariate analyses revealed that the timing of bTS was an independent predictor of PFS and OS (PFS, hazard ratio 4.09, p < 0.0001; OS, hazard ratio 2.32, p = 0.0107). CONCLUSION: The timing of bTS was an independent predictor of survival in patients with mRCC who received first-line TKIs. PMID- 27549786 TI - Investigating Patterns of Participation in an Online Support Group for Problem Drinking: a Social Network Analysis. AB - PURPOSE: This study contributes to emerging literature on online health networks by modeling communication patterns between members of a moderated online support group for problem drinking. Using social network analysis, we described members' patterns of joint participation in threads, parsing out the role of site moderators, and explored differences in member characteristics by network position. METHODS: Posts made to the online support group of Alcohol Help Centre during 2013 were structured as a two-mode network of members (n = 205) connected via threads (n = 506). Metrics included degree centrality, clique membership, and tie strength. RESULTS: The network consisted of one component and no cliques of members, although most made few posts and a small number communicated only with the site's moderators. Highly active members were older and tended to have started posting prior to 2013. The distribution of members across threads varied from threads containing posts by one member to others that connected multiple members. Moderators accounted for sizable proportions of the connectivity between both members and threads. CONCLUSIONS: After 5 years of operation, the AHC online support group appears to be fairly cohesive and stable, in the sense that there were no isolated subnetworks comprised of specific types of members or devoted to specific topics. Participation and connectedness at the member-level was varied, however, and tended to be low on average. The moderators were among the most central in the network, although there were also members who emerged as central and dedicated contributors to the online discussions across topics. Study findings highlight a number of areas for consideration by online support group developers and managers. PMID- 27549787 TI - Economic assessment of US physician participation in short-term medical missions. AB - BACKGROUND: Short term medical missions (STMMs) are a form of unregulated and unsanctioned, grass roots, direct medical service aid from wealthier countries to low and middle income countries. The US leads the world in STMM activity. The magnitude of monetary and man power inputs towards STMMs is not clear. The objective of this study is to estimate the prevalence of physician participation in STMMs from the US and the related expenditures of cash and resources. METHODS: An online survey solicited information on physician participation in STMMs. Responses regarding costs were aggregated to estimate individual and global expenditures. RESULTS: Sample statistics from 601 respondent physicians indicate an increasing participation by US physicians in STMMs. Including opportunity cost, average total economic inputs for an individual physician pursuing an STMM exceed $11,000. Composite expenditures for STMM deployment from the US are estimated at near $3.7 billion annually and the resource investment equates with nearly 5800 physician fulltime equivalents. CONCLUSIONS: STMM participation and mission numbers have been increasing in the millennium. The aggregate costs are material when benchmarked against formal US aid transfers. Understanding the drivers of physician volunteerism in this activity is thereby worthy of study and relevant to future policy deliberation. PMID- 27549788 TI - Prevalence and factors associated with nontuberculous mycobacteria in non-cystic fibrosis bronchiectasis: a multicenter observational study. AB - BACKGROUND: Data on the prevalence of and factors associated with nontuberculous mycobacteria (NTM) in patients with non-cystic fibrosis (CF) bronchiectasis are limited. Our aim was to determine the prevalence and factors associated with isolation of NTM in this population. METHODS: We performed a multicenter observational study of historical cohorts comprising consecutive patients with non-CF bronchiectasis and at least 2 sputum samples cultured for mycobacteria over a period of 5 years. RESULTS: The study population included 218 adult patients (61.9 % women) with a mean (SD) age of 55.7 (16) years and a mean (SD) of 5.1 (3.3) cultures/patient. NTM was isolated from sputum in 18 patients (8.3 %). Of these, 5 patients (28 %) met the American Thoracic Society criteria for NTM disease. Mycobacterium avium complex was the most frequently isolated microorganism (9 patients, 4.1 %). The variables independently associated with isolation of NTM were FVC >= 75 % predicted (OR, 4.84; 95 % CI 1.47 to 15.9; p < 0.05), age >= 50 years (OR, 4.74; 95 % CI 1.25 to 17.97; p < 0.05), and body mass index (BMI) <= 23 kg/m(2) (OR, 2.97; 95 % CI 1.03-8.58; p < 0.05). Patients with these three characteristics had a 40 % probability of having at least one isolation of NMT. CONCLUSIONS: A significant number of patients with non-CF bronchiectasis are positive for the isolation of NTM. M. avium complex is the most frequently isolated mycobacteria. FVC >= 75 % predicted, age >= 50 years, and a BMI <= 23 kg/m(2) were independently associated with the presence of NTM in patients with non-CF bronchiectasis. PMID- 27549790 TI - Positive Illusions in the Academic Context: A Longitudinal Study of Academic Self Enhancement in College. AB - In the present research, we examined academic self-enhancement in students (N = 264) followed longitudinally through 4 years of college. We used social comparison (i.e., better-than-average ratings) and self-insight (i.e., criterion based) approaches to assess the degree to which students self-enhanced in their self-perceptions of academic ability, with SAT scores, high school grade point average (GPA), and college GPA used as criterion measures. We also examined ethnic variability in academic self-enhancement. We found that academic self enhancement (a) increased or decreased over the 4 years of college, depending on its operationalization, (b) tended to be adaptive according to social comparison indices, and (c) demonstrated a trajectory that differed by ethnicity, but ethnicity did not moderate the effect of academic self-enhancement on outcomes. We discuss the implications of the findings for debates about the adaptive value of self-enhancement, the magnitude of cultural differences, and how best to conceptualize and operationalize the construct. PMID- 27549791 TI - Comment on: Should functionality and activities of daily living be considered aside from mortality in the management of hip fractures? PMID- 27549789 TI - The role of Epac in the heart. AB - As one of the most important second messengers, 3',5'-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have since disclosed its important functions in various tissues in the body. Recently, observations of genetically manipulated mice in various pathogenic models have begun to reveal the in vivo significance of previous in vitro or cellular-level findings. Here, we focused on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. Accordingly, developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases. PMID- 27549792 TI - Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis. AB - : The goal of this prospective study was to assess non-steroidal anti inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10-20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease. TRIAL REGISTRATION NUMBER: DRKS00004940. PMID- 27549793 TI - Effects of China's New Rural Cooperative Medical Scheme on reducing medical impoverishment in rural Yanbian: An alternative approach. AB - BACKGROUD: This study aimed to measure the poverty head count ratio and poverty gap of rural Yanbian in order to examine whether China's New Rural Cooperative Medical Scheme has alleviated its medical impoverishment and to compare the results of this alternative approach with those of a World Bank approach. METHODS: This cross-sectional study was based on a stratified random sample survey of 1,987 households and 6,135 individuals conducted in 2008 across eight counties in Yanbian Korean Autonomous Prefecture, Jilin province, China. A new approach was developed to define and identify medical impoverishment. The poverty head count ratio, relative poverty gap, and average poverty gap were used to measure medical impoverishment. Changes in medical impoverishment after the reimbursement under the New Rural Cooperative Medical Scheme were also examined. RESULTS: The government-run New Rural Cooperative Medical Scheme reduced the number of medically impoverished households by 24.6 %, as well as the relative and average gaps by 37.3 % and 38.9 %, respectively. CONCLUSIONS: China's New Rural Cooperative Medical Scheme has certain positive but limited effects on alleviating medical impoverishment in rural Yanbian regardless of how medical impoverishment is defined and measured. More governmental and private-sector efforts should therefore be encouraged to further improve the system in terms of financing, operation, and reimbursement policy. PMID- 27549794 TI - Transcriptome comparison reveals key candidate genes in response to vernalization of Oriental lily. AB - BACKGROUND: Oriental hybrid lily 'Sorbonne', a very important cut flower for lily, is enjoyed great popularity in the world, but it must experience a period of low winter temperature to initiate or accelerate the flowering process. To gain a better understanding of the temperature signaling pathway and the molecular metabolic reactions involved in the vernalization response, a genome wide transcriptional analysis using RNA-Seq was performed. RESULTS: 188,447,956 sequencing reads was assembled into 66,327 unigenes and showed similarity to known proteins in the Swiss-Prot protein database, and 2,893, 30,406 and 60,737 unigenes aligned to existing sequences in the KEGG, COG, and GO databases. Based on qRT-PCR results, we studied the expression of three signal regulation pathways genes-the plant hormones signal transduction (LoAP2, LoIAA1, LoARF10), the DNA methylation (LoCMT, LoFLD), and vernalizatin pathway (LoFLC, LoVRN1, LoVRN2, LoFT, LoSOC1, LoLFY, LoSVP) in the immature flower buds of Oriental hybrid lily. In addition, we identified two vernalizaiton-related genes (LoSVP and LoVRN1) from the cDNA library, which appear to be promising candidates for playing key roles in the development and response of flowering in Oriental lily plants, and LoSVP had a function in delaying flowering but LoVRN1could promote flowering early. CONCLUSIONS: We collected a sample for transcriptome sequencing and comparison when the bulb's apical meristem was in the time of floral transition when the apical meristem had not converted into the morphological differentiation process, which helped to obtain more genes playing key roles in the floral induction pathways. The upstream and downstream relationship between different genes were forecasted by the analysis of genes' expression levels in a wide range of time. Future research that is targeted towards how genes interact on each other, which will promote establishing and perfecting the molecular mechanisms of floral induction pathway by vernalization. PMID- 27549795 TI - Study of the degradation of a multidrug transporter using a non-radioactive pulse chase method. AB - Proteins are constantly synthesized and degraded in living cells during their growth and division, often in response to metabolic and environmental conditions. The synthesis and breakdown of proteins under different conditions reveal information about their mechanism of function. The metabolic incorporation of non natural amino acid azidohomoalanine (AHA) and subsequent labeling via click chemistry emerged as a non-radioactive strategy useful in the determination of protein kinetics and turnover. We used the method to monitor the degradation of two proteins involved in the multidrug efflux in Escherichia coli, the inner membrane transporter AcrB and its functional partner membrane fusion protein AcrA. Together they form a functional complex with an outer membrane channel TolC to actively transport various small molecule compounds out of E. coli cells. We found that both AcrA and AcrB lasted for approximately 6 days in live E. coli cells, and the stability of AcrB depended on the presence of AcrA but not on active efflux. These results lead to new insight into the multidrug resistance in Gram-negative bacteria conferred by efflux. PMID- 27549796 TI - Intact lipid imaging of mouse brain samples: MALDI, nanoparticle-laser desorption ionization, and 40 keV argon cluster secondary ion mass spectrometry. AB - We have investigated the capability of nanoparticle-assisted laser desorption ionization mass spectrometry (NP-LDI MS), matrix-assisted laser desorption ionization (MALDI) MS, and gas cluster ion beam secondary ion mass spectrometry (GCIB SIMS) to provide maximum information available in lipid analysis and imaging of mouse brain tissue. The use of Au nanoparticles deposited as a matrix for NP-LDI MS is compared to MALDI and SIMS analysis of mouse brain tissue and allows selective detection and imaging of groups of lipid molecular ion species localizing in the white matter differently from those observed using conventional MALDI with improved imaging potential. We demonstrate that high-energy (40 keV) GCIB SIMS can act as a semi-soft ionization method to extend the useful mass range of SIMS imaging to analyze and image intact lipids in biological samples, closing the gap between conventional SIMS and MALDI techniques. The GCIB SIMS allowed the detection of more intact lipid compounds in the mouse brain compared to MALDI with regular organic matrices. The 40 keV GCIB SIMS also produced peaks observed in the NP-LDI analysis, and these peaks were strongly enhanced in intensity by exposure of the sample to trifluororacetic acid (TFA) vapor prior to analysis. These MS techniques for imaging of different types of lipids create a potential overlap and cross point that can enhance the information for imaging lipids in biological tissue sections. Graphical abstract Schematic of mass spectral imaging of a mouse brain tissue using GCIB-SIMS and MALDI techniques. PMID- 27549797 TI - A novel chiral stationary phase HPLC-MS/MS method to discriminate between enzymatic oxidation and auto-oxidation of phosphatidylcholine. AB - To elucidate the role of enzymatic lipid peroxidation in disease pathogenesis and in food deterioration, we recently achieved stereoselective analysis of phosphatidylcholine hydroperoxide (PCOOH) possessing 13S-hydroperoxy-9Z,11E octadecadienoic acid (13(S)-9Z,11E-HPODE) using HPLC-MS/MS with a CHIRALPAK OP (+) column. Because enzymatic oxidation progresses concurrently with auto oxidation, we need to distinguish them further. Here, we attempted such an analysis. First, we used lipoxygenase, linoleic acid, and lysophosphatidylcholine (LPC) to synthesize the enzymatic oxidation product 13(S)-9Z,11E-HPODE PC, and the auto-oxidation products 13(RS)-9Z,11E-HPODE PC and 13(RS)-9E,11E-HPODE PC, which were used as standards to test the ability of various columns to separate the enzymatic oxidation product from auto-oxidation products. Separation was achieved by connecting in series two columns with different properties: CHIRALPAK OP (+) and CHIRALPAK IB-3. The CHIRALPAK OP (+) column separated 13(R)-9Z,11E HPODE PC and 13(S)-9Z,11E-HPODE PC, whereas CHIRALPAK IB-3 enabled separation of 13(S)-9Z,11E-HPODE PC and 13(RS)-9E,11E-HPODE PC. The results for the analysis of both enzymatically oxidized and auto-oxidized lecithin (an important phospholipid mixture in vivo and in food) indicate that our method would be useful for distinguishing enzymatic oxidation and auto-oxidation reactions. Such information will be invaluable for elucidating the involvement of PCOOH in disease pathogenesis and in food deterioration. PMID- 27549801 TI - Ethics Across the Curriculum: Prospects for Broader (and Deeper) Teaching and Learning in Research and Engineering Ethics. AB - The movements to teach the responsible conduct of research (RCR) and engineering ethics at technological universities are often unacknowledged aspects of the ethics across the curriculum (EAC) movement and could benefit from explicit alliances with it. Remarkably, however, not nearly as much scholarly attention has been devoted to EAC as to RCR or to engineering ethics, and RCR and engineering ethics educational efforts are not always presented as facets of EAC. The emergence of EAC efforts at two different institutions-the Illinois Institute of Technology and Utah Valley University (UVU)-provide counter examples. The remarkably successful UVU initiative gave birth to EAC as a scholarly movement and to the associated Society for Ethics Across the Curriculum. EAC initiatives at the Colorado School of Mines, however, point up continuing institutional resistances to EAC. Finally, comparative reflection on successes and failures can draw some lessons for the future. One suggestion is that increasing demands for accountability and pedagogical research into what works in teaching and learning offers special opportunities. PMID- 27549798 TI - Absenteeism due to mental health problems and systems for return to work: an internet-based unmatched case-control study. AB - PURPOSE: The aim of this study was to investigate the risk factors for absenteeism due to mental health problems with regard to company characteristics and systems for return to work in Japan. METHODS: This was an Internet-based unmatched case-control study. Two hundred and fifty-eight workers who experienced over 28 days of sick leave due to mental health problems (cases) and 258 workers who have not taken sick leave (controls) were recruited. Company characteristics and the awareness and presence of systems for return to work were analysed as indicators of absenteeism. RESULTS: A total of 501 workers were included in the analysis. Females were less likely to experience absenteeism when adjustments were made for both the awareness and presence of systems [odds ratio (OR) = 0.51 and 0.41, respectively]. Large companies showed an increased risk of having absentee workers than small companies. The awareness of a gradual resumption system and the presence of a sick pay system were related to absenteeism (OR = 2.75 and 2.40, respectively). CONCLUSIONS: The awareness and presence of systems for return to work are related to the long-term absenteeism. The predictors of sex and company size are also related to the experience of the long-term absenteeism. To understand the effect of systems for return to work on absenteeism due to mental problems, further studies are needed. PMID- 27549802 TI - High-quality genome assembly of channel catfish, Ictalurus punctatus. AB - BACKGROUND: The channel catfish (Ictalurus punctatus), a species native to North America, is one of the most important commercial freshwater fish in the world, especially in the United States' aquaculture industry. Since its introduction into China in 1984, both cultivation area and yield of this species have been dramatically increased such that China is now the leading producer of channel catfish. To aid genomic research in this species, data sets such as genetic linkage groups, long-insert libraries, physical maps, bacterial artificial clones (BAC) end sequences (BES), transcriptome assemblies, and reference genome sequences have been generated. Here, using diverse assembly methods, we provide a comparable high-quality genome assembly for a channel catfish from a breeding stock inbred in China for more than three generations, which was originally imported to China from North America. FINDINGS: Approximately 201.6 gigabases (Gb) of genome reads were sequenced by the Illumina HiSeq 2000 platform. Subsequently, we generated high quality, cost-effective and easily assembled sequences of the channel catfish genome with a scaffold N50 of 7.2 Mb and 95.6 % completeness. We also predicted that the channel catfish genome contains 21,556 protein-coding genes and 275.3 Mb (megabase pairs) of repetitive sequences. CONCLUSIONS: We report a high-quality genome assembly of the channel catfish, which is comparable to a recent report of the "Coco" channel catfish. These generated genome data could be used as an initial platform for molecular breeding to obtain novel catfish varieties using genomic approaches. PMID- 27549803 TI - The case-crossover design via penalized regression. AB - BACKGROUND: The case-crossover design is an attractive alternative to the classical case-control design which can be used to study the onset of acute events if the risk factors of interest vary in time. By comparing exposures within cases at different time periods, the case-crossover design does not rely on control subjects which can be difficult to acquire. However, using the standard method of maximum likelihood, resulting risk estimates can be heavily biased when the prevalence to risk factors is very low (or very high). METHODS: To overcome the problem of low risk factor prevalences, penalized conditional logistic regression via the lasso (least absolute shrinkage and selection operator) has been proposed in the literature as well as related methods such as the Firth correction. We apply and compare several penalized regression approaches in the context of a case-crossover analysis of the European Study of Severe Cutaneous Adverse Reactions (EuroSCAR; 1997-2001). RESULTS: Out of 30 drugs, standard methods only correctly classified 17 drugs (including some highly implausible risk estimates), while penalized methods correctly classified 22 drugs. CONCLUSION: Penalized methods generally yield better risk classifications and much more plausible risk estimates for the EuroSCAR study than standard methods. As these novel techniques can be easily implemented using available R packages, we encourage routine use of penalized conditional logistic regression for case-crossover data. PMID- 27549805 TI - Tribunal orders university to release data from PACE chronic fatigue study. PMID- 27549804 TI - Improved border sharpness of post-infarct scar by a novel self-navigated free breathing high-resolution 3D whole-heart inversion recovery magnetic resonance approach. AB - The border zone of post-infarction myocardial scar as identified by late gadolinium enhancement (LGE) has been identified as a substrate for arrhythmias and consequently, high-resolution 3D scar information is potentially useful for planning of electrophysiological interventions. This study evaluates the performance of a novel high-resolution 3D self-navigated free-breathing inversion recovery magnetic resonance pulse sequence (3D-SN-LGE) vs. conventional 2D breath hold LGE (2D-LGE) with regard to sharpness of borders (SBorder) of post infarction scar. Patients with post-infarction scar underwent two magnetic resonance examinations for conventional 2D-LGE and high-resolution 3D-SN-LGE acquisitions (both 15 min after 0.2 mmol/kg Gadobutrol IV) at 1.5T. In the prototype 3D-SN-LGE sequence, each ECG-triggered radial steady-state-free precession read-out segment is preceded by a non-slice-selective inversion pulse. Scar volume and SBorder were assessed on 2D-LGE and matching reconstructed high resolution 3D-SN-LGE short-axis slices. In 16 patients (four females, 58 +/- 10y) all scars visualized by 2D-LGE could be identified on 3D-SN-LGE (time between 2D LGE and 3D-SN-LGE 48 +/- 53 days). A good agreement of scar volume by 3D-SN-LGE vs. 2D-LGE was found (Bland-Altman: -3.7 +/- 3.4 ml, correlation: r = 0.987, p < 0.001) with a small difference in scar volume (20.5 (15.8, 35.2) ml vs. 24.5 (20.0, 41.9)) ml, respectively, p = 0.002] and a good intra- and interobserver variability (1.1 +/- 4.1 and -1.1 +/- 11.9 ml, respectively). SBorder of border "scar to non-infarcted myocardium" was superior on 3D-SN-LGE vs. 2D-LGE: 0.180 +/ 0.044 vs. 0.083 +/- 0.038, p < 0.001. Detection and quantification of myocardial scar by 3D-SN-LGE is feasible and accurate in comparison to 2D-LGE. The high spatial resolution of the 3D sequence improves delineation of scar borders. PMID- 27549807 TI - Current Therapeutics, Their Problems and Thiol Metabolism as Potential Drug Targets in Leishmaniasis. AB - Leishmaniasis is one of the six diseases regarded most neglected by World Health Organization which is predominant in developing countries. Clinically, among the different forms of leishmaniasis, visceral leishmaniasis is the most fatal, serious disease, in which several organs of the body such as liver and spleen are affected. A limited number of drugs against leishmaniasis are available for the treatment and also, no suitable vaccine is available for the control of leishmaniasis. However, the drugs currently used for the treatment of leishmaniasis have serious side effects as well as drug resistance issues. Therefore, search for alternative drugs to treat leishmaniasis is widely pursued; often targeting the metabolic pathways of Leishmania which are either absent or different from the mammalian host and involved in survival, pathogenesis and drug resistance of parasite. Herein, we review the aspects of chemotherapy of leishmaniasis by synthetic and natural drugs, their mechanism of action, pharmacokinetics and involvement in the development of drug resistance. Furthermore, regulatory role of trypanothione as key molecule for redox homeostasis via antioxidant enzymes and proteins like tryparedoxin, tryparedoxin peroxidase, superoxide dismutase, and ascorbate peroxidase are presented. We have comprehensively discussed thiol metabolism as drug target and its role in parasite survival. PMID- 27549806 TI - Axl signaling induces development of natural killer cells in vitro and in vivo. AB - Natural killer (NK) cells have been well known to play a critical role in innate immunity, but they are also capable of regulating adaptive immunity through the induction of T cell-mediated memory response and B cell-mediated autoimmune response. NK cells are differentiated from hematopoietic stem cells (HSCs) in the bone marrow (BM), and a series of surface molecules are expressed on NK cells in a differentiation stage-specific manner. Axl receptor tyrosine kinase is originally identified as homeostatic regulators for antigen-presenting cells, and its ligand, growth-arrest-specific gene 6 (Gas6), has been reported to promote cell survival, proliferation, and migration, but their regulatory role in the development and effector function of NK cells is not yet fully understood. In this study, to investigate whether Axl is required for the regulation of NK cell development, the expression of mature NK (mNK) cell-specific receptors and NK cell-associated genes was analyzed in the differentiated HSCs-derived NK cells in vitro and the NK cells harvested from Axl-/- mice. We found that agonistic anti Axl antibody or recombinant Gas6 specifically upregulated the expression of mNK cell-specific receptors, such as LY49A, Ly49G2, Ly49C/F/I, NKG2A/C/E (1.5- to 3.5 fold increase), and NK cell-associated genes, such as IL-2Rbeta (2.3- or 2.4-fold increase), Perforin (4.1- or 2.1-fold increase), IL-15Ralpha (2.14- or 2.04-fold increase), and IFN-gamma (3.3- or 2.8-fold increase) compared to each isotype control, whereas it was abrogated by treatment of Axl-Ig. Anti-Axl antibody or rGas6 also induced a 2.5- or 1.9-fold increase in the proliferation of developing NK cells compared to each control, respectively. mNK cell populations expressing mNK cell-specific receptors were reduced about twofold in NK cells differentiated from HSCs of Axl-/- mice compared with those of wild-type mice. Furthermore, the triggering of Axl signaling by agonistic anti-Axl antibody promoted the cytolytic activity (1.5- to 1.9-fold increase) against target tumor cells. In B16F10 melanoma-bearing mice, the number of metastatic colonies was decreased by 83 % by the administration of mNK cells treated with anti-Axl antibody compared to control Ig. These data suggest that Axl plays an essential role in the regulation of NK cell development as well as NK effector function. PMID- 27549808 TI - Extracellular expression of glutamate decarboxylase B in Escherichia coli to improve gamma-aminobutyric acid production. AB - Escherichia coli overexpressing glutamate decarboxylase GadB can produce gamma aminobutyric acid with addition of monosodium glutamate. The yield and productivity of gamma-aminobutyric acid might be significantly improved if the overexpressed GadB in E. coli cells can be excreted outside, where it can directly transforms monosodium glutamate to gamma-aminobutyric acid. In this study, GadB was fused to signal peptides TorA or PelB, respectively, and overexpressed in E. coli BL21(DE3). It was found that TorA could facilitate GadB secretion much better than PelB. Conditions for GadB secretion and gamma aminobutyric acid production were optimized in E. coli BL21(DE3)/pET20b-torA gadB, leading the secretion of more than half of the overexpressed GadB. Fed batch fermentation for GadB expression and gamma-aminobutyric acid production of BL21(DE3)/pET20b-torA-gadB was sequentially performed in one fermenter; 264.4 and 313.1 g/L gamma-aminobutyric acid were obtained with addition of monosodium glutamate after 36 and 72 h, respectively. PMID- 27549809 TI - Left and right ventricular dyssynchrony and strains from cardiovascular magnetic resonance feature tracking do not predict deterioration of ventricular function in patients with repaired tetralogy of Fallot. AB - BACKGROUND: Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF. METHODS: A database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, >6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and RV peak global longitudinal strains. Three outcomes were defined, whose changes were assessed over time: RV end-diastolic volume, and RV and LV ejection fraction. Multivariate linear mixed models were fit to investigate relationships of outcomes to predictors and ten potential baseline confounders. RESULTS: One hundred fifty-three patients with rTOF (23 +/- 14 years, 50 % male) were included. The mean follow-up duration between the first and last CMR was 2.9 +/- 1.3 years. After adjustment for confounders, none of the 7 primary predictors were significantly associated with change over time in the 3 outcome variables. Only 1-17 % of the variability in the change over time in the outcome variables was explained by the baseline predictors and potential confounders. CONCLUSIONS: In patients with repaired tetralogy of Fallot, ventricular dyssynchrony and global strain derived from cine CMR were not significantly related to changes in ventricular size and function over time. The ability to predict deterioration in ventricular function in patients with rTOF using current methods is limited. PMID- 27549810 TI - A reverse factual analysis of the association between smoking and memory decline in China. AB - BACKGROUND: Whether smoking accelerates memory recession has been a topic of significant research. However, randomised controlled trials are not easy to carry out, and does not comply with the ethics of research. And observation method which based on the most readily observed data is easy to draw the wrong conclusions without adjustment. The memory difference between smokers and non smokers may not really represent the real differences between their memories. METHODS: In response to these limitations, we adopt propensity score method to match the samples and solve the estimated selection bias and confounding bias on elderlies aged 60 years and over based on Chinese Longitudinal Healthy Longevity Survey (2011) data. The respondents are divided into non-smokers, people who used to smoke but not now, and people who used to smoke and still now. To balance the similarity between different groups on their propensity score weighted distributions of pretreatment covariates, we use generalized boosted models to estimate the multiply treatment propensity scores. RESULTS: The results show that compared with non-smokers, people who used to smoke and still now respectively have a decrease 0.0283, 0.0735, 0.0091 on self-evaluation memory, daily living activities, and cognitive function. People who used to smoke but not now have a decrease 0.0224 on daily living activities, while have an increase 0.0054 and 0.0104 on self-evaluation memory, and cognitive function. CONCLUSION: The PSM has considerable utility to control pre-treatment imbalances on observed covariates in non-randomised or observational data. PMID- 27549812 TI - Changing roles of academic societies due to globalization. AB - Because of the globalization of environment around the academic society, the expected roles have changed significantly. In this short communication, we present the current situation in our international activities of the Japan Radiological Society, particularly in the academic activities and clinical practice. Establishing and reinforcing international network is one process of their promotion. PMID- 27549811 TI - Managing chronic widespread pain in primary care: a qualitative study of patient perspectives and implications for treatment delivery. AB - BACKGROUND: Clinical guidelines recommend a combination of physical, pharmacological and psychological treatments for chronic widespread pain, but published accounts of treatment acceptability are lacking. METHODS: Semi structured interviews (n = 44) nested within a randomised controlled trial comparing the clinical and cost effectiveness of prescribed exercise, cognitive behavioural therapy (CBT), and combined exercise and CBT to treatment as usual for adults with chronic widespread pain. RESULTS: Three main themes emerged from the data: i) the illness context (how people experience chronic pain and associated health services); ii) the identity context (how people react to their symptoms and accommodate these within themselves) and iii) the intervention context (the extent and manner by which the trial interventions models aligned with these responses). Referral to a prescribed exercise programme resonated most closely with participants' tendency to attribute pain to a structural or mechanical defect. Psychological therapy brought with it connotations of social judgement, deviance and stigma. Experience of psychological therapy often exceeded expectation. Participants who engaged in cognitive reflection and behavioural adaptation reported an upward identity shift independent of increased physical exercise behaviour. CONCLUSIONS: A logical rationale for a health intervention is in itself insufficient to ensure uptake and participation. Potential differences in treatment meaning emphasise the importance of acknowledging different phases of illness acceptance and of providing the most appropriate treatment option for the stage of reconciliation. Health service providers must not only understand people's own perceptions of chronic widespread pain but also the broader spheres of influence in which this pain is experienced. PMID- 27549813 TI - Interaction with specific HSP90 residues as a scoring function: validation in the D3R Grand Challenge 2015. AB - Here is reported the development of a novel scoring function that performs remarkably well at identifying the native binding pose of a subset of HSP90 inhibitors containing aminopyrimidine or resorcinol based scaffolds. This scoring function is called PocketScore, and consists of the interaction energy between a ligand and three residues in the binding pocket: Asp93, Thr184 and a water molecule. We integrated PocketScore into a molecular docking workflow, and used it to participate in the Drug Design Data Resource (D3R) Grand Challenge 2015 (GC2015). PocketScore was able to rank 180 molecules of the GC2015 according to their binding affinity with satisfactory performance. These results indicate that the specific residues considered by PocketScore are determinant to properly model the interaction between HSP90 and its subset of inhibitors containing aminopyrimidine or resorcinol based scaffolds. Moreover, the development of PocketScore aimed at improving docking power while neglecting the prediction of binding affinities, suggesting that accurate identification of native binding poses is a determinant factor for the performance of virtual screens. PMID- 27549814 TI - Azahar: a PyMOL plugin for construction, visualization and analysis of glycan molecules. AB - Glycans are key molecules in many physiological and pathological processes. As with other molecules, like proteins, visualization of the 3D structures of glycans adds valuable information for understanding their biological function. Hence, here we introduce Azahar, a computing environment for the creation, visualization and analysis of glycan molecules. Azahar is implemented in Python and works as a plugin for the well known PyMOL package (Schrodinger in The PyMOL molecular graphics system, version 1.3r1, 2010). Besides the already available visualization and analysis options provided by PyMOL, Azahar includes 3 cartoon like representations and tools for 3D structure caracterization such as a comformational search using a Monte Carlo with minimization routine and also tools to analyse single glycans or trajectories/ensembles including the calculation of radius of gyration, Ramachandran plots and hydrogen bonds. Azahar is freely available to download from http://www.pymolwiki.org/index.php/Azahar and the source code is available at https://github.com/agustinaarroyuelo/Azahar . PMID- 27549815 TI - Ganoderic Acid A Targeting beta-Catenin in Wnt Signaling Pathway: In Silico and In Vitro Study. AB - Wnt signaling pathways are the group of signaling transduction controlling the embryonic development, cell proliferation, cell migration, cell fate specification, and body axis pattern. Nuclear accumulation of beta-catenin in Wnt signaling is a widely recognized marker of poor cancer prognosis which regulates fat and glucose metabolism. Ganoderic acid is a triterpene isolated from fungus Ganoderma lucidum renowned for its pharmacological effects. The present study revealed the mechanistic study of beta-catenin with 50 isoforms of ganoderic acid by molecular docking using Maestro 9.6 (Schrodinger Inc) in Wnt signaling pathway. Molecular docking reveals the binding interaction of beta-catenin and ganoderic acid A with GScore (-9.44), kcal/mol, lipophilic EvdW (-2.86), electro (-0.72), Glide emodel (-50.401), MM-GBSA (-87.441), H bond (-1.91) with Lys 180 and Asn 220 residues involved in hydrogen bonding. Qikprop analyzed the absorption, distribution, metabolism, excretion, and toxicity and confirmed that most of the isoforms satisfies Lipinski rule but needs little modifications in their structure. The ganoderic acid A is the best-docked isoforms which inhibits the proliferation, viability, and intracellular ROS of pancreatic cancer RIN-5F cells in a dose-dependent manner. PMID- 27549856 TI - Argininemia as a cause of severe chronic stunting in a low-resource developing country setting: a case report. AB - BACKGROUND: Argininemia is rare inborn error of metabolism which, when untreated, presents in late infancy with growth delay and developmental regression. In developed countries, argininemia is diagnosed early by newborn screening and is treated immediately with a protein-restricted diet. In developing countries, diagnosis may be delayed by the assumption that stunting is related to malnutrition alone. CASE PRESENTATION: We describe the diagnosis and treatment of argininemia in a 60-month-old Kaqchikel Maya girl in rural Guatemala. The patient initially presented with severe stunting and developmental regression. The initial diagnosis of argininemia was made by a screening test in dried blood spots and confirmed with urine and serum amino acid profiles. The patient was treated with a low-protein diet using locally available foods, leading to significant improvement in her growth and development. CONCLUSIONS: This case demonstrates that the identification, diagnosis and treatment of IEM in developing countries are increasingly feasible, as well as ethically imperative. Providers working with malnourished children in developing countries should suspect IEM in malnourished children who do not respond to standard therapies. PMID- 27549857 TI - Author's reply. PMID- 27549858 TI - Perspectives in Medicinal Chemistry. PMID- 27549859 TI - Editorial (Thematic Issue: Heat Shock Proteins in Disease - From Molecular Mechanisms to Therapeutics). PMID- 27549861 TI - Genetics and molecular mapping of resistance to Plasmodiophora brassicae pathotypes 2, 3, 5, 6, and 8 in rutabaga (Brassica napus var. napobrassica). AB - Clubroot disease, caused by Plasmodiophora brassicae, is a threat to the production of Brassica crops including oilseed B. napus. In Canada, several pathotypes of this pathogen, such as pathotypes 2, 3, 5, 6, and 8, were identified, and resistance to these pathotypes was found in a rutabaga (B. napus var. napobrassica) genotype. In this paper, we report the genetic basis and molecular mapping of this resistance by use of F2, backcross (BC1), and doubled haploid (DH) populations generated from crossing of this rutabaga line to a susceptible spring B. napus canola line. The F1, F2, and BC1 populations were evaluated for resistance to pathotype 3, and the DH population was evaluated for resistance to pathotypes 2, 3, 5, 6, and 8. A 3:1 segregation in F2 and a 1:1 segregation in BC1 were found for resistance to pathotype 3, and a 1:1 segregation was found in the DH population for resistance to all pathotypes. Molecular mapping by using the DH population identified a genomic region on chromosome A8 carrying resistance to all five pathotypes. This suggests that a single gene or a cluster of genes, located in this genomic region, is involved in the control of resistance to these pathotypes. PMID- 27549860 TI - Optimal treatment and stochastic modeling of heterogeneous tumors. AB - In this work we review past articles that have mathematically studied cancer heterogeneity and the impact of this heterogeneity on the structure of optimal therapy. We look at past works on modeling how heterogeneous tumors respond to radiotherapy, and take a particularly close look at how the optimal radiotherapy schedule is modified by the presence of heterogeneity. In addition, we review past works on the study of optimal chemotherapy when dealing with heterogeneous tumors. REVIEWERS: This article was reviewed by Thomas McDonald, David Axelrod, and Leonid Hanin. PMID- 27549862 TI - Episiotomy and the risk of severe perineal injuries among Korean women. AB - PURPOSE: We examined the frequency of severe perineal injuries according to the use of episiotomy in vaginal deliveries of Korean women. MATERIALS AND METHODS: This is a retrospective cohort study in which 358 consecutive parturients were included. Women were divided into episiotomy (n = 115) and no episiotomy (n = 243) groups. The main outcome was the occurrence of severe (third or fourth degree) perineal injuries. Delivery records and medical documents were reviewed to collect the data. Parametric and nonparametric tests were used as appropriate. RESULTS: There were no significant differences in the frequency of severe perineal injuries between two groups (6.1% (7/115) in episiotomy versus 3.7% (9/243) in no episiotomy group, p = 0.308). Anterior perineal laceration was more frequent (40.3% (98/243) vs. 18.3% (21/115), p < 0.001), but intact perineum was found in 15.6% (38/243) of women in no episiotomy group. Logistic regression analysis was performed to evaluate independent risk factors in the occurrence of severe perineal injuries including maternal age, parity, performance of episiotomy, head position at delivery, length of second stage of labor, birth weight, head circumference, and the use of vacuum during delivery. Only birthweight was a significant factor in predicting severe perineal injuries, and performance of episiotomy did not increase nor decrease the risk of severe perineal injury. CONCLUSIONS: There was no difference in the occurrence of severe perineal injuries according to the use of episiotomy. PMID- 27549863 TI - Asymmetric Mannich Reaction of Isatin-Based Ketimines with alpha Diazomethylphosphonates Catalyzed by Chiral Silver Phosphate. AB - An efficient asymmetric Mannich reaction of isatin-based ketimines with alpha diazomethylphosphonates has been developed using a chiral binaphthanol-derived silver phosphate as the catalyst. This reaction allowed the construction of a series of chiral oxindoles bearing a quaternary stereocenter and amino group at the C3 position with up to 95% yields and 99% ee. Those products could be further transformed into promising densely functionalized compounds by merging of the oxindole and beta-aminophosphonate. PMID- 27549864 TI - Complicated malaria symptoms associated with Plasmodium vivax among patients visiting health facilities in Mendi town, Northwest Ethiopia. AB - BACKGROUND: Malaria is still a major health problem in some parts of the world. Plasmodium falciparum is the common pathogenic parasite and is responsible for majority of malaria associated deaths. Recently the other benign parasite, P. vivax, is reported to cause life threatening severe malaria complications. Thus, this study was aimed to assess incidence of severe malaria symptoms caused by P. vivax parasite in some malaria endemic areas of Ethiopia. MATERIALS AND METHODS: Presumptive malaria patients (all age groups) seeking medication at the selected health facilities in Mendi town, Northwest Ethiopia, were recruited for the study. Socio-demographic, clinical and parasitological characteristics were assessed following standard procedures. Data was analyzed using descriptive statistics, chi-square test and relative risk. RESULTS: Of the 384 patients enrolled in the study for P. vivax mono-infection, 55 (14.3 %) of them were fulfilled at least one of the WHO criteria for severe malaria indicators. Some of these clinical manifestations were: prostration 14 (25.45 %), persistent vomiting 9 (16.36 %), respiratory distress 6 (10.9 %), hypoglycemia 5 (9.1 %), hyperpyrexia 8 (14.5 %), and severe anemia 13 (23.63 %). Differences in parasite load did not affect the frequency of some severe malaria symptoms. However, severe anemia, prostration, and persistent vomiting were significantly affected (P < 0.05) by relatively higher load of parasitemia, (OR = 3.8, 95 % CI, 1.1 13.7; OR = 4.4, 95 % CI, 1.4-13.9; and OR = 7, 95 % CI, 1.8-27.4) respectively. CONCLUSION: P.vivax associated severe malaria symptoms observed in this study is supportive evidence for the notion that P.vivax is no longer benign parasite but rather virulent. Thus, to meet international and regional targets of malaria eradication, a holistic prevention and control approaches should be designed. PMID- 27549866 TI - Metastatic tubercular abscess associated with bone and lymph node involvement. PMID- 27549865 TI - Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome. AB - Recent evidence has shown that the sperm epigenome is vulnerable to dynamic modifications arising from a variety of paternal environment exposures and that this legacy can serve as an important determinant of intergenerational inheritance. It has been postulated that such exchange is communicated to maturing spermatozoa via the transfer of small non-protein-coding RNAs (sRNAs) in a mechanism mediated by epididymosomes; small membrane bound vesicles released by the soma of the male reproductive tract (epididymis). Here we confirm that mouse epididymosomes encapsulate an impressive cargo of >350 microRNAs (miRNAs), a developmentally important sRNA class, the majority (~60%) of which are also represented by the miRNA signature of spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma. We also documented substantial changes in the epididymosome miRNA cargo, including significant fold changes in almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNA species between mouse epididymosomes and spermatozoa to afford novel insight into a mechanism of intercellular communication by which the sRNA payload of sperm can be selectively modified during their post-testicular maturation. PMID- 27549867 TI - Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open label, evaluator-blinded study. AB - BACKGROUND: Finasteride and dutasteride are inhibitors of the enzyme 5-alpha reductase which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride inhibits both type I and type II 5-alpha-reductase while finasteride inhibits only the type II enzyme. As both isoenzymes are present in hair follicles, it is likely that dutasteride is more effective than finasteride. AIMS: To compare the efficacy, safety and tolerability of dutasteride and finasteride in men with androgenetic alopecia. METHODS: Men with androgenetic alopecia between 18 and 40 years of age were randomized to receive 0.5 mg dutasteride or 1 mg finasteride daily for 24 weeks. The primary efficacy variables were hair counts (thick and thin) in the target area from modified phototrichograms and global photography evaluation by blinded and non-blinded investigators. The secondary efficacy variable was subjective assessment using a preset questionnaire. Patients were assessed monthly for side effects. RESULTS: Ninety men with androgenetic alopecia were recruited. The increase in total hair count per cm[2] representing new growth was significantly higher in dutasteride group (baseline- 223 hair; at 24 weeks- 246 hair) compared to finasteride group (baseline- 227 hair; at 24 weeks- 231 hair). The decrease in thin hair count per cm[2] suggestive of reversal of miniaturization was significantly higher in dutasteride group (baseline- 65 hair; at 24 weeks- 57 hair) compared to finasteride group (baseline- 67 hair; at 24 weeks- 66 hair). Both the groups showed a similar side effect profile with sexual dysfunction being the most common and reversible side effect. LIMITATIONS: Limitations include the short duration of the study (6 months), the small sample size and the fact that it was an open-label study. CONCLUSIONS: Dutasteride was shown to be more efficacious than finasteride and the side-effect profiles were comparable. PMID- 27549868 TI - Aplasia cutis congenita, group 5 without fetus papyraceus in two newborns. PMID- 27549869 TI - Pyoderma gangrenosum: A clinico-epidemiological study. AB - BACKGROUND: Pyoderma gangrenosum is a neutrophilic dermatosis of unknown etiology, with inconstant systemic associations and a variable prognosis. AIMS: To study the clinical features and systemic associations of pyoderma gangrenosum and its response to treatment. METHODS: All patients diagnosed to have pyoderma gangrenosum at the dermatology department of the Government Medical College, Kozhikode, from January 01, 2005 to December 31, 2014 were included in this prospective study. RESULTS: During the 10-year study period, 61 patients were diagnosed to have pyoderma gangrenosum. A male predilection was noted. The most common clinical type was ulcerative pyoderma gangrenosum (90.2%). More than 60% of patients had lesions confined to the legs; 78.7% had a single lesion and 27.9% had systemic associations. Most patients required systemic steroids. Patients with disease resistant to steroid therapy were treated with intravenous immunoglobulin G and split-thickness skin grafts under immunosuppression induced by dexamethasone pulse therapy. All except one patient attained complete disease resolution. LIMITATIONS: The main limitation of our study was the small sample size. CONCLUSIONS: The male predilection documented by us was contrary to most previous studies. We found split-thickness skin graft to be a useful option in resistant cases. More prospective studies may enable the formulation of better diagnostic criteria for pyoderma gangrenosum and improve its management. PMID- 27549870 TI - The effect of statins on severity of psoriasis: A systematic review. AB - BACKGROUND: Psoriasis is becoming increasingly recognized as a chronic systemic inflammatory disease. Statins are generally well-tolerated drugs with pleiotropic effects including decreasing inflammation and may have the potential to reduce psoriasis severity. AIMS: To examine whether oral statins reduce the severity of psoriatic skin disease. METHODS: We searched MEDLINE, EMBASE and adapted for Google Scholar, Cochrane Central Register for Controlled Trials and Clinical trials.gov to January 6, 2016. We primarily examined randomized controlled trials that assessed the change in PASI score over a follow-up period of at least 8 weeks, for participants with an established diagnosis of psoriasis taking an oral statin versus placebo or other active treatment. Beyond this, we also examined other interventional studies that investigated the effect of statins on psoriasis severity using other designs. We extracted efficacy and adverse event data. The two study authors examined issues of study quality and study inclusion independently. RESULTS: Three studies were identified which measured the change in psoriasis severity using PASI, comparing statin with placebo or standard therapy alone in a prospective, randomized study design; these showed conflicting results. However, among the excluded studies, majority of which used a single arm, non-placebo controlled study design, most showed an improvement in PASI scores after statin use. LIMITATIONS: Included studies were of limited sample size and quality. They were not amenable to pooled analysis. CONCLUSIONS: This review highlights the paucity of high quality, randomized, double-blinded, placebo-controlled trials investigating the effects of statins on psoriasis severity using clinically objective measures. There is insufficient evidence that the use of oral statins as an adjunctive therapy can reduce the severity of psoriasis. PMID- 27549871 TI - Multiple hyperpigmented patches in Waardenburg syndrome type 1: An unusual presentation. PMID- 27549872 TI - Bottom-up fabrication of artery-mimicking tubular co-cultures in collagen-based microchannel scaffolds. AB - We developed a robust bottom-up approach to construct open-ended, tubular co culture constructs that simulate the human vascular morphology and microenvironment. By design, these three-dimensional artificial vessels mimic the basic architecture of an artery: a collagen-rich extracellular matrix (as the tunica externa), smooth muscle cells (SMCs) (as the tunica media), and an endothelial cell (EC) lining (as the tunica interna). A versatile needle-based fabrication technique was employed to achieve controllable arterial layouts within a PDMS-hosted collagen microchannel scaffold (330 +/- 10 MUm in diameter): (direct co-culture) a SMC/EC bilayer to follow the structure of an arteriole-like segment; and (encapsulated co-culture) a lateral SMC multilayer covered by an EC monolayer lining to simulate the architecture of a larger artery. Optical and fluorescence microscopy images clearly evidenced the progressive cell elongation and sprouting behavior of SMCs and ECs along the collagen gel contour and within the gel matrix under static co-culture conditions. The progressive cell growth patterns effectively led to the formation of a tubular co-culture with an internal endothelial lining expressing prominent CD31 (cluster of differentiation 31) intercellular junction markers. During a 4-day static maturation period, the artery constructs showed modest alteration in the luminal diameters (i.e. less than 10% changes from the initial measurements). This argues in favor of stable and predictable arterial architecture achieved via the proposed fabrication protocols. Both co-culture models showed a high glucose metabolic rate during the initial proliferation phase, followed by a temporary quiescent (and thus, mature) stage. These proof-of-concept models with a controllable architecture create an important foundation for advanced vessel manipulations such as the integration of relevant physiological functionality or remodeling into a vascular disease mimicking tissue. PMID- 27549874 TI - Preventing Diabetic Retinopathy Progression. PMID- 27549873 TI - Hip fracture incidence 2003-2013 and projected cases until 2050 in Austria: a population-based study. AB - OBJECTIVES: Elevated hip fracture incidence is a major public health problem looming to aggravate in industrialized countries due to demographic developments. We report hip fracture incidence and expected future cases from Vorarlberg, the westernmost province of Austria, results potentially representative of Central European populations. METHODS: Crude and standardized hip fracture incidence rates in Vorarlberg 2003-2013 are reported. Based on the age-specific incidence in 2013 or trends 2003-2013, we predict hip fractures till 2050. RESULTS: Female age-standardized hip fracture incidence decreased 2005-2013, whereas for men, the trend was rather unclear. Uncorrected forecasts indicate that by 2050, female and male cases will each have more than doubled from 2015 in all demographic core scenarios. Corrected by incidence trends before 2013, cases are expected to drop among women but rise among men. CONCLUSIONS: We anticipate rising hip fracture numbers in Vorarlberg within the next decades, unless prevention programs that presumably account for decreasing incidence rates, particularly among women since 2005, take further effect to counteract the predicted steady increase due to demographic changes. Concomitantly, augmented endeavors to target the male population by these programs are needed. PMID- 27549875 TI - Bevacizumab for Retinopathy of Prematurity: Treatment When Pathology Is Embedded in a Normally Developing Vascular System. PMID- 27549876 TI - Eyelid Merkel Cell Carcinoma. PMID- 27549877 TI - Giant Eyelid Molluscum Contagiosum in a Child with AIDS. PMID- 27549878 TI - Ocular Manifestation of Leukemia Cutis. PMID- 27549880 TI - Corneal Leukoma with Features of Both Sclerocornea and Peter's Anomaly. PMID- 27549879 TI - Optical Coherence Tomography Angiography Findings in Coats' Disease. PMID- 27549881 TI - In the Fold of a Macular Hole. PMID- 27549882 TI - Free-Floating Pigmented Vitreous Cyst: Optical Coherence Tomography Findings. PMID- 27549883 TI - Corrigendum. PMID- 27549884 TI - Corrigendum. PMID- 27549885 TI - Reply. PMID- 27549886 TI - Re: Kang et al.: Discrepancy in subfoveal choroidal thickness in healthy adults with isometropia (Ophthalmology 2015;122:2363-4). PMID- 27549887 TI - Re: Kuang et al.: Estimating lead time gained by optical coherence topography in detecting glaucoma before development of visual field defects (Ophthalmology 2015;122:2002-9). PMID- 27549888 TI - Re: Baskaran et al.: Anterior segment imaging predicts incident gonioscopic angle closure (Ophthalmology 2015;122:2380-2). PMID- 27549889 TI - Reply. PMID- 27549890 TI - Re: Shorstein et al.: Comparative effectiveness of three prophylactic strategies to prevent clinical macular edema after phacoemulsification surgery (Ophthalmology 2015;122:2450-6). PMID- 27549891 TI - Re: Wang et al.: Comparison of newer intraocular lens power calculation methods for eyes after corneal refractive surgery (Ophthalmology 2015;122:2443-9). PMID- 27549892 TI - Reply. PMID- 27549893 TI - Reply. PMID- 27549894 TI - Diagnostic conundrums in antenatal presentation of a skeletal dysplasia with description of a heterozygous C-propeptide mutation in COL1A1 associated with a severe presentation of osteogenesis imperfecta. AB - Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis. It is important to make a diagnosis in antenatal presentation of skeletal dysplasias to inform diagnosis, predict prognosis, provide accurate recurrence risks, and options for prenatal genetic testing in future pregnancies. Prenatal ultrasound scanning is a useful tool to detect several skeletal dysplasias and sonographic measurements serve as reliable indicators of lethality. The lethality depends on various factors including gestational age at which features are identified, size of the chest and progression of malformations. Although, it is important to type the skeletal presentation as accurately as possible, this is not always possible in an antenatal presentation and it is important to acknowledge this uncertainty. In the case of a live birth, it is always important to reassess the infant. Osteogenesis imperfecta (OI) is a heterogeneous group of disorders characterized by fragile bones. Here, we report an infant with severe OI born following a twin pregnancy in whom the bone disease is caused by a heterozygous pathogenic mutation, c.4160C >T, p.(Ala1387Val) located in the C-propeptide region of COL1A1. An assumption of lethality antenatally complicated his management in early life. We discuss this patient with particular emphasis on the neonatal presentation of a severe skeletal dysplasia and the lessons that may be learned in such situations. (c) 2016 Wiley Periodicals, Inc. PMID- 27549895 TI - The role of traditional health practitioners in Rural KwaZulu-Natal, South Africa: generic or mode specific? AB - BACKGROUND: Traditional health practitioners (THPs) play a vital role in the health care of the majority of the South African population and elsewhere on the African continent. However, many studies have challenged the role of THPs in health care. Concerns raised in the literature include the rationale, safety and effectiveness of traditional health practices and methods, as well as what informs them. This paper explores the processes followed in becoming a traditional healer and how these processes are related to THP roles. METHODS: A qualitative research design was adopted, using four repeat group discussions with nine THPs, as part of a larger qualitative study conducted within the HIV Treatment as Prevention trial in rural South Africa. THPs were sampled through the local THP association and snowballing techniques. Data collection approaches included photo-voice and community walks. The role identity theory and content analysis were used to explore the data following transcription and translation. RESULTS: In the context of rural Northern KwaZulu-Natal, three types of THPs were identified: 1) Isangoma (diviner); 2) Inyanga (one who focuses on traditional medical remedies) and 3) Umthandazi (faith healer). Findings revealed that THPs are called by ancestors to become healers and/or go through an intensive process of learning about traditional medicines including plant, animal or mineral substances to provide health care. Some THPs identified themselves primarily as one type of healer, while most occupied multiple healing categories, that is, they practiced across different healing types. Our study also demonstrates that THPs fulfil roles that are not specific to the type of healer they are, these include services that go beyond the uses of herbs for physical illnesses or divination. CONCLUSIONS: THPs serve roles which include, but are not limited to, being custodians of traditional African religion and customs, educators about culture, counsellors, mediators and spiritual protectors. THPs' mode specific roles are influenced by the processes by which they become healers. However, whichever type of healer they identified as, most THPs used similar, generic methods and practices to focus on the physical, spiritual, cultural, psychological, emotional and social elements of illness. PMID- 27549896 TI - The information filter: how dentists use diet diary information to give patients clear and simple advice. AB - OBJECTIVES: Diet diaries are recommended for dentists to monitor children's sugar consumption. Diaries provide multifaceted dietary information, but patients respond better to simpler advice. We explore how dentists integrate information from diet diaries to deliver useable advice to patients. METHODS: As part of a questionnaire study of general dental practitioners (GDPs) in Northwest England, we asked dentists to specify the advice they would give a hypothetical patient based upon a diet diary case vignette. A sequential mixed method approach was used for data analysis: an initial inductive content analysis (ICA) to develop coding system to capture the complexity of dietary assessment and delivered advice. Using these codes, a quantitative analysis was conducted to examine correspondences between identified dietary problems and advice given. From these correspondences, we inferred how dentists reduced problems to give simple advice. RESULTS: A total of 229 dentists' responses were analysed. ICA on 40 questionnaires identified two distinctive approaches of developing diet advice: a summative (summary of issues into an all-encompassing message) and a selective approach (selection of a main message approach). In the quantitative analysis of all responses, raw frequencies indicated that dentists saw more problems than they advised on and provided highly specific advice on a restricted number of problems (e.g. not eating sugars before bedtime 50.7% or harmful items 42.4%, rather than simply reducing the amount of sugar 9.2%). Binary logistic regression models indicate that dentists provided specific advice that was tailored to the key problems that they identified. CONCLUSION: Dentists provided specific recommendations to address what they felt were key problems, whilst not intervening to address other problems that they may have felt less pressing. PMID- 27549897 TI - A rapid, instrument-free, sample-to-result nucleic acid amplification test. AB - The prototype demonstrated here is the first fully integrated sample-to-result diagnostic platform for performing nucleic acid amplification tests that requires no permanent instrument or manual sample processing. The multiplexable autonomous disposable nucleic acid amplification test (MAD NAAT) is based on two-dimensional paper networks, which enable sensitive chemical detection normally reserved for laboratories to be carried out anywhere by untrained users. All reagents are stored dry in the disposable test device and are rehydrated by stored buffer. The paper network is physically multiplexed to allow independent isothermal amplification of multiple targets; each amplification reaction is also chemically multiplexed with an internal amplification control. The total test time is less than one hour. The MAD NAAT prototype was used to characterize a set of human nasal swab specimens pre-screened for methicillin-resistant Staphylococcus aureus (MRSA) bacteria. With qPCR as the quantitative reference method, the lowest input copy number in the range where the MAD NAAT prototype consistently detected MRSA in these specimens was ~5 * 10(3) genomic copies (~600 genomic copies per biplexed amplification reaction). PMID- 27549899 TI - Living with traumatic brain injury in a rural setting: supports and barriers across the continuum of care. AB - PURPOSE: Traumatic brain injury (TBI) is prevalent in Kentucky and comes with a high cost in care and quality of life for individuals and caregivers affected. Many people living with the condition of TBI have unmet needs. Research among people living with TBI in rural areas is limited. The purposes of this study were to (1) increase understanding of the lived experience of people with TBI and caregivers in rural regions of Kentucky across the continuum of their care and (2) provide their perspectives on barriers and facilitators of optimal function and well-being. METHODS: A qualitative descriptive interview study was conducted by a multidisciplinary team. Content analysis was completed with data-derived coding and iterative modifications to analysis, coalescing codes into categories and themes. RESULTS: Thirteen people with TBI and six caregivers participated in the interview. Categories that emerged in analysis included the experiences under each locus of care; themes included relationships, functional competence, and participation in meaningful activity. CONCLUSION: Relationships represented both barriers and facilitators of well-being. Major unmet needs persisted in terms of medical problems, support for caregivers, community linkages, and participation in meaningful activities. Recommendations are made regarding avenues for addressing unmet needs. Implications for Rehabilitation People with TBI are living with chronic conditions and may need intensive rehabilitation after the injury and intermittent rehabilitation throughout life to develop and maintain functional competence. Rehabilitation providers need to understand the unique aspects of the rural home environment to which a patient will be discharged (e.g., mountainous terrain, lack of transportation, dimensions of home) and communicate with rural providers directly. Rehabilitation providers need additional focus on improving patient's and caregiver's abilities to advocate for themselves. Patients with TBI should be referred to vocational rehabilitation as soon as possible to make the transition to meaningful activity at home more of a possibility. PMID- 27549900 TI - Characterization of a monocyanide model of FeFe hydrogenases - highlighting the importance of the bridgehead nitrogen for catalysis. AB - An azadithiolate bridged monocyanide derivative [Fe2(adt)(CO)5(CN)]- of [Fe2(adt)(CO)4(CN)2]2- has been prepared and extensively characterized as a model of the [FeFe]-hydrogenase active site, using a combination of FTIR spectroscopy, electrochemical methods and catalytic assays with chemical reductants. The presence of two basic nitrogen sites opens up multiple protonation pathways, enabling catalytic proton reduction. To our knowledge [Fe2(adt)(CO)5(CN)]- represents the first example of a cyanide containing [FeFe]-hydrogenase active site mimic capable of catalytic H2 formation in aqueous media. PMID- 27549901 TI - Comparison of oral steroids with tonsillectomy plus steroid pulse therapy in patients with IgA nephropathy. AB - BACKGROUND: Treatment of IgA nephropathy (IgAN) in Japan has recently changed, from oral prednisolone (oPSL) to tonsillectomy plus steroid pulse (TSP) therapy. However, a few studies have compared their efficacy and safety. METHODS: IgAN patients diagnosed in our institution between 1991 and 2013, treated with TSP or oPSL, aged >=16 years, with >=1 g/day proteinuria, and estimated glomerular filtration rate (eGFR) >=30 ml/min/1.73 m2, and no other renal disease were selected. Baseline clinical and histological findings, clinical outcomes, and adverse events were compared. Clinical remission (CR) was defined as <0.3 g/day proteinuria and <5 urinary red blood cells per high-powered field. RESULTS: Sixty six patients were identified; after propensity score adjustment, 26 patients were selected in each group. CR rates were significantly higher at 12 (30.8 % vs. 3.9 %), 36 (47.3 % vs. 7.9 %), and 72 (57.8 % vs. 20.1 %) months (p < 0.01), and the renal survival rate, defined as the development of a 25 % reduction from baseline eGFR, was significantly higher at 12 (96.2 % vs. 69.2 %), 36 (96.2 % vs. 61.5 %), and 72 (96.2 % vs. 41.0 %) months in the TSP than the oPSL group (p < 0.001). Multivariate analysis showed that TSP was the only independent factor associated with CR (hazard ratio, 3.58; 95 % confidence interval, 1.32-10.91, p = 0.01). The number of patients with adverse events was significant lower in TSP group than in oPSL group (11.5 % vs. 34.6 %, p = 0.04). CONCLUSIONS: CR rates are higher; protection of renal function and prevention from adverse events were superior with TSP than with oPSL in patients with IgAN and moderate-to-severe proteinuria. PMID- 27549903 TI - Hip and knee replacement-do we need to bother about psychiatry? PMID- 27549902 TI - Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect. AB - Drug addiction is a chronic brain disorder characterized by the compulsive repeated use of drugs. The reinforcing effect of repeated use of drugs on reward plays an important role in morphine-induced addictive behaviors. The nucleus accumbens (NAc) is an important site where morphine treatment produces its reinforcing effect on reward. However, how morphine treatment produces its reinforcing effect on reward in the NAc remains to be clarified. In the present study, we studied the influence of morphine treatment on the effects of DA and observed whether morphine treatment could directly change glutamatergic synaptic transmission in the NAc. We also explored the functional significance of morphine induced potentiation of glutamatergic synaptic transmission in the NAc at behavioral level. Our results show that (1) morphine treatment removes the inhibitory effect of DA on glutamatergic input onto NAc neurons; (2) morphine treatment potentiates glutamatergic input onto NAc neurons, especially the one from the basolateral amygdala (BLA) to the NAc; (3) blockade of glutamatergic synaptic transmission in the NAc or ablation of projection neurons from BLA to NAc significantly decreases morphine treatment-induced increase in locomotor activity. These results suggest that morphine treatment enhances glutamatergic input onto neurons of the NAc via both disinhibitory and stimulating effect and therefore increases locomotor activity. PMID- 27549905 TI - Factors influencing the fabrication of albumin-bound drug nanoparticles (ABDns): Part II. Albumin-bound carbamazepine nanoparticles (ABCns). AB - Carbamazepine (CBZ) is a BCS Class II drug with poor solubility profile. In order to improve the physicochemical properties of CBZ, albumin (HSA)-bound CBZ nanoparticles (ABCns) were prepared. Drug-loading studies indicated that monomeric ABCns can be fabricated by self-assembly of anhydrous form III of CBZ and HSA in molar ratios of 1:1 or 2:1 within 0.5 h in phosphate buffer pH 7.4 with particle size in the range of 10-20 nm. Approximately 73-76% of the CBZ was encapsulated within HSA and 20-40% CBZ was released from the ABCns over 8 days. In conclusion, novel ABCns can be fabricated with sustained-release of CBZ for over 8 days which can significantly improve the physicochemical profile of CBZ. PMID- 27549904 TI - General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis. AB - OBJECTIVE: Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. STUDY DESIGN: Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. METHODS: Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. RESULTS: Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. CONCLUSION: Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. LEVEL OF EVIDENCE: 3b. Laryngoscope, 2016 127:296-302, 2017. PMID- 27549906 TI - Seizure-related modulation of systemic arterial blood pressure in focal epilepsy. AB - OBJECTIVE: Cardiorespiratory function alterations are commonly observed with epileptic seizures and may lead to syncope and sudden unexpected death in epilepsy (SUDEP). Although most previous research has focused on controlling heart rate (HR) and respiration, little is known about seizure-related regulation of systemic blood pressure (BP). Herein, we have investigated whether the periictal modulation of systemic BP and HR depends on seizure characteristics. METHODS: Systemic arterial BP, HR, and peripheral capillary oxygen saturation (SPO2 ) were continuously and noninvasively monitored using the ccNexfin device in those epilepsy patients undergoing video-electroencephalography (EEG) telemetry. Data are given as mean +/- standard deviation (SD). RESULTS: Forty five seizures in 37 patients were included. In focal seizures (FS, n = 35), the mean arterial BP (MAP) increased by 33 +/- 35% and the HR by 53 +/- 44%, whereas the SPO2 remained unaltered. The MAP and HR increases were significantly greater in FS with alterations in consciousness than in those without. For those FS that evolved to bilateral convulsive seizures (BCS, n = 10), all of the ictal recordings were compromised by artifacts. However, 2 min after seizure cessation, the MAP was enhanced by only 16 +/- 14% and returned to a baseline slightly below preictal levels after 5 min, whereas the HR was increased by 77 +/- 33% and remained elevated throughout the postictal phase. SIGNIFICANCE: Periictal regulation of systemic BP and HR displays distinct patterns depending on the type of seizure with focal onset. These changes were unrelated to alterations in SPO2 . The potential clinical implications of these findings are discussed in the article. PMID- 27549908 TI - Trends and outcomes of chronic kidney disease in intensive care: a 5-year study. AB - BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing in Australia and is independently associated with a higher risk of hospitalisation and death. Australian data may be useful in guiding improved hospital management of this growing cohort of patients. AIM: To assess and compare the trends and outcomes of CKD patients requiring hospital and intensive care unit (ICU) admission at a tertiary referral hospital and state public hospitals. METHODS: We conducted a retrospective analysis of all acute care admissions to St Vincent's Hospital Melbourne and all Victorian public hospitals using the Victorian Admitted Episodes Data Set (VAED) for the years 2010-2014 to determine CKD prevalence, demographic and outcome associations. The Elixhauser ICD-10 comorbidity classification of renal failure was used to identify CKD (ElixRF). Chi-squared test, Kruskal-Wallis test and logistic regression were used for analysis. RESULTS: A total of 101 817 patients was included from our institution, with 6.4% classified as having ElixRF. ELixRF increased from 5.2% in 2010 to 8.6% in 2014 for all hospital admissions and from 8.3% to 13.3% for ICU admissions. ElixRF was associated with longer hospital and ICU length of stay, male gender, older age, higher comorbidity and independently with increased mortality. The VAED contained 2 044 507 episodes for the same period with similar trends and associations. CONCLUSIONS: CKD prevalence amongst patients admitted to hospital and ICU is increasing and is associated with worse outcomes. ElixRF may be a useful administrative flag for nephrologist involvement in care and for prompting consideration of advanced care planning. PMID- 27549910 TI - Electrochemical Catalyst-Support Effects and Their Stabilizing Role for IrOx Nanoparticle Catalysts during the Oxygen Evolution Reaction. AB - Redox-active support materials can help reduce the noble-metal loading of a solid chemical catalyst while offering electronic catalyst-support interactions beneficial for catalyst durability. This is well known in heterogeneous gas-phase catalysis but much less discussed for electrocatalysis at electrified liquid solid interfaces. Here, we demonstrate experimental evidence for electronic catalyst-support interactions in electrochemical environments and study their role and contribution to the corrosion stability of catalyst/support couples. Electrochemically oxidized Ir oxide nanoparticles, supported on high surface area carbons and oxides, were selected as model catalyst/support systems for the electrocatalytic oxygen evolution reaction (OER). First, the electronic, chemical, and structural state of the catalyst/support couple was compared using XANES, EXAFS, TEM, and depth-resolved XPS. While carbon-supported oxidized Ir particle showed exclusively the redox state (+4), the Ir/IrOx/ATO system exhibited evidence of metal/metal-oxide support interactions (MMOSI) that stabilized the metal particles on antimony-doped tin oxide (ATO) in sustained lower Ir oxidation states (Ir(3.2+)). At the same time, the growth of higher valent Ir oxide layers that compromise catalyst stability was suppressed. Then the electrochemical stability and the charge-transfer kinetics of the electrocatalysts were evaluated under constant current and constant potential conditions, where the analysis of the metal dissolution confirmed that the ATO support mitigates Ir(z+) dissolution thanks to a stronger MMOSI effect. Our findings raise the possibility that MMOSI effects in electrochemistry-largely neglected in the past-may be more important for a detailed understanding of the durability of oxide-supported nanoparticle OER catalysts than previously thought. PMID- 27549909 TI - Drug dispensings among elderly in the year before colon cancer diagnosis versus matched cancer-free controls. AB - WHAT IS KNOWN AND OBJECTIVE: The concomitant use of multiple drugs is common among the general population of elderly. The aim of this study was to provide an overview of which drugs are dispensed to elderly in the year before colon cancer diagnosis and to compare this with cancer-free controls. METHODS: Data from the Eindhoven Cancer Registry were linked to the PHARMO Database Network. Patients with colon cancer aged >=70 years were included and matched with controls on gender, year of birth and postal code. Proportions of cases and controls with >=1 dispensing of each WHO ATC-2-level drug during the total year and during each quarter of the year were calculated and differences between cases and controls tested. RESULTS AND DISCUSSION: Proportion of cases with >=1 drug dispensing was highest for drugs for constipation (cases vs. controls 58% vs. 10%), antithrombotics (42% vs. 33%), drugs for acid-related disorders (35% vs. 22%), antibacterials (34% vs. 24%), agents acting on the renin-angiotensin system (33% vs. 27%), beta-blockers (33% vs. 23%), lipid-modifying agents (29% vs. 22%), diuretics (29% vs. 21%), psycholeptics (25% vs. 18%) and antianaemics (23% vs. 6%). The proportion of cases with >=1 drug dispensing increased from the first to the last quarter of the year for drugs for constipation (7%-53%), drugs for acid related disorders (16%-27%), antibacterials (12%-16%), beta-blockers (26%-28%), psycholeptics (15%-19%) and antianaemics (6%-18%). Elevated proportions of cases with >=1 drug dispensing for several drugs are mostly related to comorbidity, although increasing proportions of cases with >=1 drug dispensing for certain drugs during the year can be attributed to the incidence of colon cancer. WHAT IS NEW AND CONCLUSION: We have provided insight into which drugs are commonly used in the year preceding colon cancer diagnosis. This may trigger general practitioners and medical specialists to further evaluate the patient. PMID- 27549907 TI - Glucose enhances indolic glucosinolate biosynthesis without reducing primary sulfur assimilation. AB - The effect of glucose as a signaling molecule on induction of aliphatic glucosinolate biosynthesis was reported in our former study. Here, we further investigated the regulatory mechanism of indolic glucosinolate biosynthesis by glucose in Arabidopsis. Glucose exerted a positive influence on indolic glucosinolate biosynthesis, which was demonstrated by induced accumulation of indolic glucosinolates and enhanced expression of related genes upon glucose treatment. Genetic analysis revealed that MYB34 and MYB51 were crucial in maintaining the basal indolic glucosinolate accumulation, with MYB34 being pivotal in response to glucose signaling. The increased accumulation of indolic glucosinolates and mRNA levels of MYB34, MYB51, and MYB122 caused by glucose were inhibited in the gin2-1 mutant, suggesting an important role of HXK1 in glucose mediated induction of indolic glucosinolate biosynthesis. In contrast to what was known on the function of ABI5 in glucose-mediated aliphatic glucosinolate biosynthesis, ABI5 was not required for glucose-induced indolic glucosinolate accumulation. In addition, our results also indicated that glucose-induced glucosinolate accumulation was due to enhanced sulfur assimilation instead of directed sulfur partitioning into glucosinolate biosynthesis. Thus, our data provide new insights into molecular mechanisms underlying glucose-regulated glucosinolate biosynthesis. PMID- 27549911 TI - Cross-border collaboration for neglected tropical disease efforts-Lessons learned from onchocerciasis control and elimination in the Mano River Union (West Africa). AB - Diseases don't respect borders, so efforts to control and eliminate diseases must also be flexible and adaptable enough to effectively reach the populations that live in the areas around national frontiers. Onchocerciasis, commonly known as river blindness is a tropical disease that has historically affected millions of people in 35 countries in Africa and Latin America. In Africa, programs and partnerships to address river blindness through mass drug administration have been active for more than 25 years. While in many cases the disease is found in isolated foci that fall entirely within national boundaries, the geographic scope of many affected areas crosses country borders. National river blindness programs are the responsibility of each nation's Ministry of Health, so in cross-border situations there is a need for effective country-country collaboration. Cross border collaboration for onchocerciasis control efforts in the countries of the Mano River Basin illustrates the positive impact of a creative model, and offers lessons for expanded application for onchocerciasis elimination as well as other neglected tropical disease (NTD) control and elimination programs. PMID- 27549912 TI - Quenching of pH-Responsive Luminescence of a Benzoindolizine Sensor by an Ultrafast Hydrogen Shift. AB - Fluorescent-sensor design requires consideration of how photochemical dynamics control properties of a sensing state. Transient absorption (TA) spectroscopy reveals an ultrafast net [1,3]-hydrogen shift following excitation of a protonated methoxy benzoindolizine (bzi) sensor in solution. These photochemical dynamics explain a quenched pH-responsive fluorescence shift and dramatically reduced fluorescence quantum yield relative to other (e. g. methyl) bzi compounds that do not tautomerize. Calculations predict the energetic and structural feasibility for rearrangement in protonated bzi compounds, such that interaction between the pi-network and strongly electron-donating methoxyl must lower the barrier for suprafacial H or H+ shift across an allylic moiety. As bzi compounds broadly exhibit pH-responsive emission shifts, chemical interactions that modulate this electronic interaction and suppress tautomerization could be used to facilitate binding- or surface-specific acid-responsive sensing. PMID- 27549913 TI - Low-dose 5-fluorouracil in combination with salicylic acid for the treatment of actinic keratoses on the hands and/or forearms - results of a non-interventional study. AB - BACKGROUND: As an in situ carcinoma, actinic keratoses should be treated early. Previous studies on the efficacy of a low-dose 0.5% 5-fluorouracil solution in combination with 10% salicylic acid (low-dose 5-FU/SA) are mostly related to lesions appearing on the head and face. In contrast, actinic keratoses (AK) lesions of the upper extremities are considered to be difficult to treat. OBJECTIVE: The efficacy of low-dose 5-FU/SA in the treatment of actinic keratoses on the hands and/or forearms was studied for the first time in this non interventional study (NIS) under practical conditions in a large patient population. In addition to the clinical course during therapy and a follow-up period, the length of application and adherence were documented. METHODS: As part of this NIS, 649 patients with AK were treated at 207 centres with low-dose 5 FU/SA. The data of the study were recorded at baseline, optionally during an intermediate examination, at the end of therapy and during a final assessment. RESULTS: The average number of AK lesions decreased during the entire observation period by 92%. Side-effects were documented only rarely in the form of local skin reactions (2%). The attending physicians assessed the efficacy, tolerability and safety of the therapy as being predominantly very good or good (in each case >=90%). CONCLUSION: AK lesions on the hands and/or forearms were effectively treated with low-dose 5-FU/SA under routine conditions in dermatological practice and the treatment was well tolerated. PMID- 27549914 TI - Dyspnea in Community-Dwelling Older Persons: A Multifactorial Geriatric Health Condition. AB - OBJECTIVES: To evaluate the associations between a broad array of cardiorespiratory and noncardiorespiratory impairments and dyspnea in older persons. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study. PARTICIPANTS: Community-dwelling persons (N = 4,413; mean age 72.6, 57.1% female, 4.5% African American, 27.2% =2) and several impairments, including those established using spirometry (forced expiratory volume in 1 second (FEV1 )), maximal inspiratory pressure (respiratory muscle strength), echocardiography, ankle-brachial index, blood pressure, whole-body muscle mass (bioelectrical impedance), single chair stand (lower extremity function), grip strength, serum hemoglobin and creatinine, Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Mental State Examination, medication use, and body mass index (BMI). RESULTS: In a multivariable logistic regression model, impairments that had strong associations with moderate to severe dyspnea were FEV1 less than the lower limit of normal (adjusted odds ratio (aOR) = 2.88, 95% confidence interval (CI) = 2.37-3.49), left ventricular ejection fraction less than 45% (aOR = 2.12, 95% CI = 1.43, 3.16), unable to perform a single chair stand (aOR = 2.10, 95% CI = 1.61-2.73), depressive symptoms (CES-D score >=16; aOR = 2.02, 95% CI = 1.26-3.23), and obesity (BMI >=30; aOR = 2.07, 95% CI = 1.67-2.55). Impairments with modest but still statistically significant associations with moderate to severe dyspnea included respiratory muscle weakness, diastolic cardiac dysfunction, grip weakness, anxiety symptoms, and use of cardiovascular and psychoactive medications (aORs = 1.31-1.71). CONCLUSION: In community-dwelling older persons, several cardiorespiratory and noncardiorespiratory impairments were significantly associated with moderate to severe dyspnea, akin to a multifactorial geriatric health condition. PMID- 27549915 TI - Do left hand reaction time advantages depend on localising unpredictable targets? AB - Asymmetries in hand movements have routinely been attributed to properties of the two cerebral hemispheres. In right-handed participants, the non-dominant left hand tends to have shorter reaction times, with the dominant right hand achieving shorter movement durations as well as higher peak velocities. The root cause of the surprising left hand RT effect has been debated, largely in the context of right hemisphere specialisation in attention, visuospatial abilities, or "premotor" processes. Mieschke et al. (Brain Cognit 45:1, 2001) and Barthelemy and Boulinguez ( Behav Brain Res 133:1, 2002) both tried to dissociate "premotor" processes explaining the left hand RT advantage, using reaching paradigms where at least one condition required target detection, but no visually guided aiming movement. Unfortunately, the studies obtained conflicting results and conclusions. In the present study, we attempted to re-examine this kind of paradigm with methodological improvements, such as using a task with higher visuospatial demands. Our results demonstrate that whilst RTs are longer as movement complexity increases across three conditions, the left hand RT advantage is present across all conditions-and no significant interaction between hand and condition was found. No significant hand differences were found in peak velocity or duration. These results suggest that the left hand RT advantage cannot be due to movement planning advantages of the right hemisphere, and instead should be attributed to sustained attention/vigilance lateralisation to the right cerebral hemisphere. PMID- 27549916 TI - Genome-wide identification, phylogeny and expressional profiles of mitogen activated protein kinase kinase kinase (MAPKKK) gene family in bread wheat (Triticum aestivum L.). AB - BACKGROUND: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are the important components of MAPK cascades, which play the crucial role in plant growth and development as well as in response to diverse stresses. Although this family has been systematically studied in many plant species, little is known about MAPKKK genes in wheat (Triticum aestivum L.), especially those involved in the regulatory network of stress processes. RESULTS: In this study, we identified 155 wheat MAPKKK genes through a genome-wide search method based on the latest available wheat genome information, of which 29 belonged to MEKK, 11 to ZIK and 115 to Raf subfamily, respectively. Then, chromosome localization, gene structure and conserved protein motifs and phylogenetic relationship as well as regulatory network of these TaMAPKKKs were systematically investigated and results supported the prediction. Furthermore, a total of 11 homologous groups between A, B and D sub-genome and 24 duplication pairs among them were detected, which contributed to the expansion of wheat MAPKKK gene family. Finally, the expression profiles of these MAPKKKs during development and under different abiotic stresses were investigated using the RNA-seq data. Additionally, 10 tissue-specific and 4 salt responsive TaMAPKKK genes were selected to validate their expression level through qRT-PCR analysis. CONCLUSIONS: This study for the first time reported the genome organization, evolutionary features and expression profiles of the wheat MAPKKK gene family, which laid the foundation for further functional analysis of wheat MAPKKK genes, and contributed to better understanding the roles and regulatory mechanism of MAPKKKs in wheat. PMID- 27549917 TI - Risk of Respiratory Distress Syndrome and Efficacy of Glucocorticoids: Are They the Same in the Normally Grown and Growth-Restricted Infant? AB - Administration of glucocorticoids (GCs) to women at risk of preterm delivery reduces the newborn's risk of respiratory distress syndrome (RDS) by 35% to 40%; however, not all infants respond to this treatment. Fetal growth restriction (FGR) increases the risk of prematurity, perinatal morbidity, and mortality. This review aims to synthesize current evidence reporting the difference in RDS risk between FGR and normally grown infants (Question 1) and whether antenatal GC administration reduces the risk of RDS morbidity in FGR infants (Question 2). Systematic searches were performed, and after screening, a total of 27 and 9 citations were eligible for inclusion for Questions 1 and 2, respectively. In order to answer the two questions, odds ratios and 95% confidence intervals were calculated for all studies. The evidence was equivocal for a difference in risk of RDS in FGR compared with normally grown infants. Despite antenatal GC administration, there was evidence suggesting that the risk of RDS persists in FGR infants. The range of risk of RDS morbidity observed between studies is likely influenced by the definitions (RDS and FGR), gestational age, and small sample sizes of FGR infants evaluated. In addition, RDS morbidity may be related to the heterogeneous nature of FGR etiologies (including maternal, placental, and/or fetal factors). Further understanding of RDS morbidity and responsiveness to current treatments in FGR infants at a range of gestational ages, larger sample sizes, and stratification according to the specific etiology of FGR, may lead to improved respiratory outcomes at birth in this obstetric subpopulation. PMID- 27549918 TI - Regional variation in the use of 1A status exceptions for pediatric heart transplant candidates: is this equitable? AB - The use of status exceptions (SE) was recently publicized as a strategy to reduce waitlist times for children awaiting heart transplant (HTx). The aim of this study was to assess SE use across UNOS regions and compare survival in patients listed using a SE to those listed by standard criteria. The OPTN database was queried for all pediatric patients listed for HTx (2000-2014). SE use was compared across UNOS regions. Survival curves were generated and compared using the log-rank test. 1A SE use is uncommon, being utilized in 108 of 4587 pediatric 1A listings (2.4%). There is significant variability in SE use across UNOS regions (0.7%-16.4% of 1A listings, P < .001). Waitlist survival is significantly higher in candidates listed using a 1A SE compared to those listed by standard criteria (P = .001) and is similar to 1B listings. Regional variation in 1A SE use has the potential to introduce bias into a system designed to be equitable. Waitlist survival in patients listed using a SE is similar to those listed status 1B, suggesting these patients may not require 1A status. Careful review of pediatric heart allocation policies is needed to optimize patient outcomes and ensure a fair and unbiased allocation system. PMID- 27549919 TI - Social Justice: A Concept Analysis. AB - Social justice is presented frequently as a core or shared value at the very foundation of nursing practice. Despite its acceptance as a core value, its use is varied and there has been inherent difficulty in establishing a definitive explanation for what is meant by social justice. As such, a clearly defined meaning for the concept of social justice does not exist in contemporary nursing literature. Following the method outlined by Walker and Avant, an analysis of the concept of social justice provides clarity to the meaning of social justice as it is used within the nursing profession, in academia, education, and practice. PMID- 27549920 TI - Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: A retrospective cohort study using a Japanese hospital database. AB - AIMS/INTRODUCTION: In treatment algorithms of type 2 diabetes mellitus in Western countries, biguanides are recommended as first-line agents. In Japan, various oral hypoglycemic agents (OHAs) are available, but prescription patterns are unclear. MATERIALS AND METHODS: Data of 7,108 and 2,655 type 2 diabetes mellitus patients in study 1 and study 2, respectively, were extracted from the Medical Data Vision database (2008-2013). Cardiovascular disease history was not considered in study 1, but was in study 2. Initial choice of OHA, adherence to its use, effect on glycated hemoglobin levels for 2 years and the second choice of OHA were investigated. RESULTS: In study 1, alpha-glucosidase inhibitor, glinide and thiazolidinedione were preferentially medicated in relatively lower glycated hemoglobin cases compared with other OHAs. The two most prevalent first prescriptions of OHAs were biguanides and dipeptidyl peptidase-4 inhibitors, and the greatest adherence was for alpha-glucosidase inhibitors. In patients treated continuously with a single OHA for 2 years, improvement in glycated hemoglobin levels was greatest for dipeptidyl peptidase-4 inhibitors. As a second OHA added to the first OHA during the first 2 years, dipeptidyl peptidase-4 inhibitors were chosen most often, especially if a biguanide was the first OHA. In study 2, targeting patients with a cardiovascular disease history, a similar tendency to study 1 was observed in the first choice of OHA, adherence and the second choice of OHA. CONCLUSIONS: Even in Japanese type 2 diabetes mellitus patients, a Western algorithm seems to be respected to some degree. The OHA choice does not seem to be affected by a cardiovascular disease history. PMID- 27549921 TI - The economic evaluation of human papillomavirus vaccination strategies against cervical cancer in women in Lao PDR: a mathematical modelling approach. AB - BACKGROUND: Cervical cancer, a preventable disease, is the third leading cause of cancer morbidity and mortality in the Lao People's Democratic Republic (Lao PDR). Since many cervical cancers are linked to human papilloma virus (HPV) infection, vaccination against this virus may lead to a reduction in these types of cancer. The study described here is the first to compare the cost-effectiveness of different HPV vaccination options in Lao PDR. METHODS: A dynamic compartment model was created. The model included routine screening activities already in place, as well as theoretical interventions that included a 10-year old girl-only vaccination programme combined with/without a 10-year old boy vaccination programme and/or a catch-up component. The simulation was run over 100 years. In base case analyses, we assumed 70 % vaccination coverage with lifelong protection and 100 % efficacy against HPV types 16/18. The outcomes of interest were the incremental cost per Disability-Adjusted Life Year (DALY) averted. RESULTS: In base case analyses, according to the WHO definition of cost-effectiveness thresholds, vaccinating 10-year-old girls was very cost-effective. Adding a catch up vaccination element for females aged 11-25 years was also very cost-effective, costing 1559 international dollars (I$) per DALY averted. Increasing the age limit of the catch-up vaccination component to 75 years old showed that this remained a cost-effective option (I$ 5840 per DALY averted). Adding a vaccination programme for 10-year-old boys was not found to be cost-effective unless a short time simulation (30 years or less) was considered, along with a catch-up vaccination component for both males and females. CONCLUSIONS: Adding a catch-up female vaccination component is more attractive than adding a 10-year-old boy vaccination component. PMID- 27549922 TI - Association between hepatitis C virus infection and Parkinson's disease. PMID- 27549923 TI - Adding sweet potato vines improve the quality of rice straw silage. AB - Rice straw and sweet potato vines are the main by-products of agricultural crops, and their disposal creates problems for the environment in the south of China. In order to establish an easy method for making rice straw silage successfully, experiments were conduct to evaluate fermentation quality and nutritive value of rice straw silages ensiled with or without sweet potato vine. Paddy rice straw (PR) and upland rice straw (UP) were ensiled alone or with sweet potato vines (SP) by a ratio of 1:1 (fresh matter basis), over 3 years. Compared with rice straw silages ensiled alone, the mixed-material silages (PR + SP, UR + SP) showed higher fermentation quality with lower propionic acid content and NH3 -N ratio of total N, and higher (P < 0.05) concentrations of lactic acid and acetic acid, resulting in decrease (P < 0.05) of dry matter loss and higher (P < 0.05) in vitro ruminal dry matter digestion. When the fermentation quality, chemical composition and in vitro rumen fermentation characteristics were considered, ensiling would be an effective way of utilization of rice straw and sweet potato vines in the regions where rice and sweet potato are harvested at same season, and the sweet potato vines have the potential to improve rice straw fermentation quality with low water soluble carbohydrate content in south of China. PMID- 27549924 TI - Interaction of polyethyleneimine-anchored copper(II) complexes with tRNA studied by spectroscopy methods and biological activities. AB - Ultraviolet-visible, emission and circular dichroism spectroscopic methods were used in transfer RNA (tRNA) interaction studies performed for polyethyleneimine copper(II) complexes [Cu(phen)(l-Tyr)BPEI]ClO4 (where phen =1,10-phenanthroline, l-Tyr = l-tyrosine and BPEI = branched polyethyleneimine) with various degrees of coordination (x = 0.059, 0.149, 0.182) in the polymer chain. The results indicated that polyethyleneimine-copper(II) complexes bind with tRNA mostly through surface binding, although other binding modes, such as hydrogen bonding and van der Waals interactions, might also be present. Dye-exclusion, sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of a polyethyleneimine-copper(II) complex with a higher degree of coordination against different cancer cell lines proved that the complex exhibited cytotoxic specificity and a significant cancer cell inhibition rate. Antimicrobial screening showed activity against some human pathogens. PMID- 27549925 TI - Accuracy of first-trimester combined test in screening for trisomies 21, 18 and 13. AB - OBJECTIVE: To examine the diagnostic accuracy of a previously developed model for the first-trimester combined test in screening for trisomies 21, 18 and 13. METHODS: This was a prospective validation study of screening for trisomies 21, 18 and 13 by assessment of a combination of maternal age, fetal nuchal translucency, fetal heart rate and serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation in 108 982 singleton pregnancies undergoing routine care in three maternity hospitals. A previously published algorithm was used to calculate patient-specific risks for trisomy 21, 18 and 13 in each patient. The detection rate (DR) and false-positive rate (FPR) at estimated risk cut-offs from 1 in 2 to 1 in 1000 were determined. The proportions of trisomies detected were compared to their expected values in different risk groups. RESULTS: In the study population, there were 108 112 (99.2%) cases with normal fetal karyotype or birth of a phenotypically normal neonate and 870 (0.8%) cases with abnormal karyotype, including trisomy 21 (n = 432), trisomy 18 (n = 166), trisomy 13 (n = 56), monosomy X (n = 63), triploidy (n = 35) or other aneuploidy (n = 118). The screen positive rates, standardized according to the maternal age distribution in England and Wales in 2011, of fetuses with abnormal or normal karyotype were compatible with those predicted from the previous model; at a risk cut-off of 1 in 100, the FPR was about 4% and the DRs for trisomies 21, 18 and 13 were 90%, 97% and 92%, respectively. There was evidence that the algorithm overestimated risk. This could, to some degree, reflect under-ascertainment in pregnancies ending in miscarriage or stillbirth. CONCLUSION: In a prospective validation study, the first-trimester combined test detected 90%, 97% and 92% of trisomies 21, 18 and 13, respectively, as well as > 95% of cases of monosomy X and triploidies and > 50% of other chromosomal abnormalities, at a FPR of 4%. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27549926 TI - Chirality imprinting and direct asymmetric reaction screening using a stereodynamic Bronsted/Lewis acid receptor. AB - Molecular recognition, activation and dynamic self-assembly with Bronsted and Lewis acids play a central role across the chemical sciences including catalysis, crystal engineering, supramolecular architectures and drug design. Despite this general advance, the utilization of the corresponding binding motifs for fast and robust quantitative chemosensing of chiral compounds in a complicate matrix has remained challenging. Here we show that a stereodynamic probe carrying complementary boronic acid and urea units achieves this goal with hydroxy carboxylic acids. Synergistic dual-site binding and instantaneous chirality imprinting result in characteristic ultraviolet and CD readouts that allow instantaneous determination of the absolute configuration, enantiomeric excess and concentration of the target compound even in complex mixtures. The robustness and practicality of this strategy for high-throughput screening purposes is demonstrated. Comprehensive sensing of only 0.5 mg of a crude reaction mixture of an asymmetric reduction eliminates cumbersome work-up protocols and minimizes analysis time, labour and waste production. PMID- 27549927 TI - On-Fly Femtosecond-Laser Fabrication of Self-Organized Plasmonic Nanotextures for Chemo- and Biosensing Applications. AB - Surface-enhanced Raman scattering (SERS) and surface-enhanced photoluminescence (SEPL) are emerging as versatile widespread methods for biological, chemical, and physical characterization in close proximity of nanostructured surfaces of plasmonic materials. Meanwhile, single-step, facile, cheap, and green technologies for large-scale fabrication of efficient SERS or SEPL substrates, routinely demonstrating both broad plasmonic response and high enhancement characteristics, are still missing. In this research, single-pulse spallative micron-size craters in a thick Ag film with their internal nanotexture in the form of nanosized tips are for the first time shown to demonstrate strong polarization-dependent enhancement of SEPL and SERS responses from a nanometer thick covering Rhodamine 6G layer with average enhancement factors of 40 and 2 * 10(6), respectively. Additionally, the first detailed experimental study is reported for physical processes, underlying the formation mechanisms of ablative nanotextures on such "thick" metal films. Such mechanisms demonstrate a complex "hybrid" fluence-dependent ablation character-appearance of spallative craters, typical for bulk material, at low fluences and formation of upright standing nanotips (frozen nanojets), usually associated with thin-film ablation, in the crater centers at higher fluences. Moreover, special emphasis was made on the possibility to reshape the nanotopography of such spallative craters through multipulse laser-induced merging of their small nanotips into larger ones. The presented approach holds promise to be one of the cheapest and easiest-to implement ways to mass-fabricate various efficient spallation-nanotextured single element plasmonic substrates for routine chemo- and biosensing, using MHz repetition-rate femtosecond fiber laser sources with multiplexed laser-beams. PMID- 27549928 TI - Fast, vacancy-free climb of prismatic dislocation loops in bcc metals. AB - Vacancy-mediated climb models cannot account for the fast, direct coalescence of dislocation loops seen experimentally. An alternative mechanism, self climb, allows prismatic dislocation loops to move away from their glide surface via pipe diffusion around the loop perimeter, independent of any vacancy atmosphere. Despite the known importance of self climb, theoretical models require a typically unknown activation energy, hindering implementation in materials modeling. Here, extensive molecular statics calculations of pipe diffusion processes around irregular prismatic loops are used to map the energy landscape for self climb in iron and tungsten, finding a simple, material independent energy model after normalizing by the vacancy migration barrier. Kinetic Monte Carlo simulations yield a self climb activation energy of 2 (2.5) times the vacancy migration barrier for 1/2<111> (<100>) dislocation loops. Dislocation dynamics simulations allowing self climb and glide show quantitative agreement with transmission electron microscopy observations of climbing prismatic loops in iron and tungsten, confirming that this novel form of vacancy-free climb is many orders of magnitude faster than what is predicted by traditional climb models. Self climb significantly influences the coarsening rate of defect networks, with important implications for post-irradiation annealing. PMID- 27549982 TI - Thirty-one psychoactive plants exempted from New Zealand's Psychoactive Substances Act 2013. PMID- 27549931 TI - Person-directed, non-pharmacological interventions for sleepiness at work and sleep disturbances caused by shift work. AB - BACKGROUND: Shift work is often associated with sleepiness and sleep disorders. Person-directed, non-pharmacological interventions may positively influence the impact of shift work on sleep, thereby improving workers' well-being, safety, and health. OBJECTIVES: To assess the effects of person-directed, non-pharmacological interventions for reducing sleepiness at work and improving the length and quality of sleep between shifts for shift workers. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase, Web of Knowledge, ProQuest, PsycINFO, OpenGrey, and OSH-UPDATE from inception to August 2015. We also screened reference lists and conference proceedings and searched the World Health Organization (WHO) Trial register. We contacted experts to obtain unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) (including cross-over designs) that investigated the effect of any person-directed, non-pharmacological intervention on sleepiness on-shift or sleep length and sleep quality off-shift in shift workers who also work nights. DATA COLLECTION AND ANALYSIS: At least two authors screened titles and abstracts for relevant studies, extracted data, and assessed risk of bias. We contacted authors to obtain missing information. We conducted meta-analyses when pooling of studies was possible. MAIN RESULTS: We included 17 relevant trials (with 556 review-relevant participants) which we categorised into three types of interventions: (1) various exposures to bright light (n = 10); (2) various opportunities for napping (n = 4); and (3) other interventions, such as physical exercise or sleep education (n = 3). In most instances, the studies were too heterogeneous to pool. Most of the comparisons yielded low to very low quality evidence. Only one comparison provided moderate quality evidence. Overall, the included studies' results were inconclusive. We present the results regarding sleepiness below. Bright light Combining two comparable studies (with 184 participants altogether) that investigated the effect of bright light during the night on sleepiness during a shift, revealed a mean reduction 0.83 score points of sleepiness (measured via the Stanford Sleepiness Scale (SSS) (95% confidence interval (CI) -1.3 to -0.36, very low quality evidence). Another trial did not find a significant difference in overall sleepiness on another sleepiness scale (16 participants, low quality evidence).Bright light during the night plus sunglasses at dawn did not significantly influence sleepiness compared to normal light (1 study, 17 participants, assessment via reaction time, very low quality evidence).Bright light during the day shift did not significantly reduce sleepiness during the day compared to normal light (1 trial, 61 participants, subjective assessment, low quality evidence) or compared to normal light plus placebo capsule (1 trial, 12 participants, assessment via reaction time, very low quality evidence). Napping during the night shiftA meta-analysis on a single nap opportunity and the effect on the mean reaction time as a surrogate for sleepiness, resulted in a 11.87 ms reduction (95% CI 31.94 to -8.2, very low quality evidence). Two other studies also reported statistically non-significant decreases in reaction time (1 study seven participants; 1 study 49 participants, very low quality evidence).A two-nap opportunity resulted in a statistically non significant increase of sleepiness (subjective assessment) in one study (mean difference (MD) 2.32, 95% CI -24.74 to 29.38, 1 study, 15 participants, low quality evidence). Other interventionsPhysical exercise and sleep education interventions showed promise, but sufficient data to draw conclusions are lacking. AUTHORS' CONCLUSIONS: Given the methodological diversity of the included studies, in terms of interventions, settings, and assessment tools, their limited reporting and the very low to low quality of the evidence they present, it is not possible to determine whether shift workers' sleepiness can be reduced or if their sleep length or quality can be improved with these interventions.We need better and adequately powered RCTs of the effect of bright light, and naps, either on their own or together and other non-pharmacological interventions that also consider shift workers' chronobiology on the investigated sleep parameters. PMID- 27549930 TI - 3D microtumors in vitro supported by perfused vascular networks. AB - There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This "organs-on chips" approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This "tumor-on-a-chip" platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID- 27549929 TI - Cognitive deficits caused by a disease-mutation in the alpha3 Na(+)/K(+)-ATPase isoform. AB - The Na(+)/K(+)-ATPases maintain Na(+) and K(+) electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na(+)/K(+)-ATPase alpha3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the alpha3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (alpha3(+/D801Y)) was generated. The alpha3(+/D801Y) mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the alpha3(+/D801Y) mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na(+)/K(+) ATPase alpha3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission. PMID- 27549983 TI - Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels. AB - There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of glioblastoma TICs required for drug discovery and development. In this paper we report a new method that encapsulates patient-derived primary glioblastoma TICs and grows them in 3 dimension thermoreversible hydrogels. Our method allows long-term culture (~50 days, 10 passages tested, accumulative ~>10(10)-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 * 10(7) cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery. PMID- 27549984 TI - Soil bacterial and fungal community dynamics in relation to Panax notoginseng death rate in a continuous cropping system. AB - Notoginseng (Panax notoginseng), a valuable herbal medicine, has high death rates in continuous cropping systems. Variation in the soil microbial community is considered the primary cause of notoginseng mortality, although the taxa responsible for crop failure remains unidentified. This study used high throughput sequencing methods to characterize changes in the microbial community and screen microbial taxa related to the death rate. Fungal diversity significantly decreased in soils cropped with notoginseng for three years. The death rate and the fungal diversity were significantly negatively correlated, suggesting that fungal diversity might be a potential bioindicator of soil health. Positive correlation coefficients revealed that Burkholderiales, Syntrophobacteraceae, Myrmecridium, Phaeosphaeria, Fusarium, and Phoma were better adapted to colonization of diseased plants. The relative abundance of Fusarium oxysporum (R = 0.841, P < 0.05) and Phaeosphaeria rousseliana (R = 0.830, P < 0.05) were positively associated with the death rate. F. oxysporum was a pathogen of notoginseng root-rot that caused seedling death. Negative correlation coefficients indicated that Thermogemmatisporaceae, Actinosynnemataceae, Hydnodontaceae, Herpotrichiellaceae, and Coniosporium might be antagonists of pathogens, and the relative abundance of Coniosporium perforans was negatively correlated with the death rate. Our findings provide a dynamic overview of the microbial community and present a clear scope for screening beneficial microbes and pathogens of notoginseng. PMID- 27549986 TI - Selective Oxidative Decarbonylative Cleavage of Unstrained C(sp(3))-C(sp(2)) Bond: Synthesis of Substituted Benzoxazinones. AB - A transition metal (TM)-free practical synthesis of biologically relevant benzoxazinones has been established via a selective oxidative decarbonylative cleavage of an unstrained C(sp(3))-C(sp(2)) bond employing iodine, sodium bicarbonate, and (t)butyl hydroperoxide in DMSO at 95 degrees C. Control experiments and Density Functional Theory (DFT) calculations suggest that the reaction involves a [1,5]H shift and extrusion of CO gas as the key steps. The extrusion of CO has also been established using PMA-PdCl2. PMID- 27549985 TI - Maternal anemia effects during pregnancy on male and female fetuses: are there any differences? AB - OBJECTIVE: Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. STUDY DESIGN: A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb <= 11 g/dl and Group B (n = 975) with Hb >= 11,1 g/dl. RESULTS: Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). CONCLUSION: Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome. PMID- 27549987 TI - Translation and Reimbursement: The Twin Challenges for Cell and Gene Therapies Reflections of an Ex-Regulator. PMID- 27549988 TI - Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell induced vaso-occlusion. AB - Sevuparin is a novel drug candidate in phase II development as a treatment for vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). As a heparin-derived polysaccharide, sevuparin has been designed to retain anti adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Here, we demonstrate that sevuparin inhibits the adhesion of human sickle red blood cells (SS-RBCs) to stimulated cultured endothelial cells in vitro. Importantly, sevuparin prevents vaso-occlusion and normalizes blood flow in an in vivo mouse model of SCD vaso occlusion. Analyses by surface plasmon resonance (SPR) and fluorescence correlation spectroscopy (FCS) demonstrate that sevuparin binds to P- and L selectins, thrombospondin, fibronectin and von Willebrand factor, all of which are thought to contribute to vaso-occlusion in SCD. Despite low anticoagulation activity, sevuparin has anti-adhesive efficacy similar to the low molecular weight heparin tinzaparin both in vitro and in vivo. These results suggest that the anti-adhesive properties rather than the anticoagulant effects of heparinoids are critical for the treatment of vaso-occlusion in SCD. Therefore, sevuparin is now being evaluated in SCD patients hospitalized for treatment of VOC. PMID- 27549989 TI - A Resident-led Initiative Improves Screening and Treatment for Vitamin D Deficiency in Patients with Hip Fractures. AB - BACKGROUND: Acute hip fractures carry a high risk of morbidity and are associated with low vitamin D levels. Improvements in screening and treating low vitamin D levels may lead to lower fall rates and a lower likelihood of additional fragility fractures. However, patients with low vitamin D levels often remain unassessed and untreated, even after they experience these fractures. QUESTIONS/PURPOSES: We wished to determine whether a resident-led initiative can improve (1) screening for and (2) treatment of vitamin D deficiency in patients with acute hip fractures. METHODS: Our department initiated a housestaff-led, quality improvement project focused on screening and treating vitamin D deficiency in patients with acute hip fractures. Screening encompassed checking serum 25-hydroxyvitamin D level during the acute hospitalization, and treating was defined as starting supplementation before discharge when the serum 25 hydroxyvitamin D level was less than 30 ng/mL. To evaluate the efficacy of this program, an administrative database identified 283 patients treated surgically for an acute hip fracture between July 2010 and June 2014. This period included 2 years before program initiation (Year 1, n = 65 patients; Year 2, n = 61 patients), the initial program year (Year 3, n = 66 patients), and the subsequent program year (Year 4, n = 91 patients). Followup was extended to 6 weeks after treatment with 9.2% (26/282) of patients lost to followup. Eight patients were excluded owing to documented intolerance of vitamin D supplementation. There were no differences regarding patient demographics, fracture type, or treatment rendered across these 4 years. The primary endpoints were the proportion of patients screened and treated for vitamin D deficiency. The secondary endpoint was the continuation of vitamin D supplementation at the patient's 6 week followup, according to the patient's medication list at that visit. This analysis included all patients, assuming those lost to followup had not continued supplementation. ANOVA and chi-square tests were used to evaluate the differences in demographic data and in screening and treating rates. RESULTS: Screening for vitamin D deficiency improved after initiation of the resident-led quality improvement program, with screening performed for 31% of patients in Year 1 (20/65; odds ratio [OR], 0.44; 95% CI, 0.26-0.75), 20% of patients in Year 2 (12/61; OR, 0.24; 95% CI, 0.13-0.46), 46% of patients in Year 3 (30/66; OR, 0.83; 95% CI, 0.51-1.35), and 88% of patients in Year 4 (80/91; OR, 7.27; 95% CI, 3.87 13.7) (p < 0.001). Vitamin D supplementation was initiated for 33% of patients in Year 1 (21/63; OR, 0.5; 95% CI, 0.30-0.84), 28% in Year 2 (17/61; OR, 0.39; 95% CI, 0.22-0.68), 50% in Year 3 (32/64; OR,1.00; 95% CI, 0.61-1.63), and 76% in Year 4 (65/86; OR, 3.10; 95% CI, 1.89-5.06) (p < 0.001). At early postoperative followup, we saw substantial improvement in the proportion of patients who continued receiving vitamin D supplementation: Year 1, 12% (8/64; OR, 0.14; 95% CI, 0.07-0.30); Year 2, 15% (9/61; OR, 0.17; 95% CI, 0.09-0.35); Year 3, 26% (16/64; OR, 0.33; 95% CI, 0.19-0.59); and Year 4, 46% (40/86; OR, 0.87; 95% CI, 0.57-1.33) (p < 0.001). CONCLUSIONS: Implementation of a resident-led quality improvement program resulted in higher rates of screening and treating vitamin D deficiency for patients with acute hip fractures. Housestaff-based initiatives may be an effective way to improve care processes that target improvements in bone health. PMID- 27549990 TI - Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model? AB - BACKGROUND: Polyetheretherketone (PEEK) has a wide range of clinical applications but does not directly bond to bone. Bulk incorporation of osteoconductive materials including hydroxyapatite (HA) into the PEEK matrix is a potential solution to address the formation of a fibrous tissue layer between PEEK and bone and has not been tested. QUESTIONS/PURPOSES: Using in vivo ovine animal models, we asked: (1) Does PEEK-HA improve cortical and cancellous bone ongrowth compared with PEEK? (2) Does PEEK-HA improve bone ongrowth and fusion outcome in a more challenging functional ovine cervical fusion model? METHODS: The in vivo responses of PEEK-HA Enhanced and PEEK-OPTIMA(r) Natural were evaluated for bone ongrowth in the form of dowels implanted in the cancellous and cortical bone of adult sheep and examined at 4 and 12 weeks as well as interbody cervical fusion at 6, 12, and 26 weeks. The bone-implant interface was evaluated with radiographic and histologic endpoints for a qualitative assessment of direct bone contact of an intervening fibrous tissue later. Gamma-irradiated cortical allograft cages were evaluated as well. RESULTS: Incorporating HA into the PEEK matrix resulted in more direct bone apposition as opposed to the fibrous tissue interface with PEEK alone in the bone ongrowth as well as interbody cervical fusions. No adverse reactions were found at the implant-bone interface for either material. Radiography and histology revealed resorption and fracture of the allograft devices in vivo. CONCLUSIONS: Incorporating HA into PEEK provides a more favorable environment than PEEK alone for bone ongrowth. Cervical fusion was improved with PEEK-HA compared with PEEK alone as well as allograft bone interbody devices. CLINICAL RELEVANCE: Improving the bone-implant interface with a PEEK device by incorporating HA may improve interbody fusion results and requires further clinical studies. PMID- 27549991 TI - Population cardiovascular health and urban environments: the Heart Healthy Hoods exploratory study in Madrid, Spain. AB - BACKGROUND: Our aim is to conduct an exploratory study to provide an in-depth characterization of a neighborhood's social and physical environment in relation to cardiovascular health. A mixed-methods approach was used to better understand the food, alcohol, tobacco and physical activity domains of the urban environment. METHODS: We conducted this study in an area of 16,000 residents in Madrid (Spain). We obtained cardiovascular health and risk factors data from all residents aged 45 and above using Electronic Health Records from the Madrid Primary Health Care System. We used several quantitative audit tools to assess: the type and location of food outlets and healthy food availability; tobacco and alcohol points of sale; walkability of all streets and use of parks and public spaces. We also conducted 11 qualitative interviews with key informants to help understanding the relationships between urban environment and cardiovascular behaviors. We integrated quantitative and qualitative data following a mixed methods merging approach. RESULTS: Electronic Health Records of the entire population of the area showed similar prevalence of risk factors compared to the rest of Madrid/Spain (prevalence of diabetes: 12 %, hypertension: 34 %, dyslipidemia: 32 %, smoking: 10 %, obesity: 20 %). The food environment was very dense, with many small stores (n = 44) and a large food market with 112 stalls. Residents highlighted the importance of these small stores for buying healthy foods. Alcohol and tobacco environments were also very dense (n = 91 and 64, respectively), dominated by bars and restaurants (n = 53) that also acted as food services. Neighbors emphasized the importance of drinking as a socialization mechanism. Public open spaces were mostly used by seniors that remarked the importance of accessibility to these spaces and the availability of destinations to walk to. CONCLUSION: This experience allowed testing and refining measurement tools, drawn from epidemiology, geography, sociology and anthropology, to better understand the urban environment in relation to cardiovascular health. PMID- 27549992 TI - Perceived Walking Speed, Measured Tandem Walk, Incident Stroke, and Mortality in Older Latino Adults: A Prospective Cohort Study. AB - Background: Walking speed is associated with functional status and all-cause mortality. Yet the relationship between walking speed and stroke, also a leading cause of disability, remains poorly understood, especially in older Latino adults who suffer from a significant burden of stroke. Methods: A total of 1,486 stroke free participants from the Sacramento Area Latino Study on Aging, aged 60 and older at baseline in 1998-1999, were followed annually through 2010. Participants reported their usual walking speed outdoors which was classified into slow, medium, or fast. We also assessed timed tandem walk ability (unable or eight or more errors vs less than eight errors). We ascertained three incident stroke endpoints: total stroke, nonfatal stroke, and fatal stroke. Using Cox proportional hazards models, we estimated hazard ratios (HRs) for stroke at different walking speed and timed tandem walk categories. Results: Over an average of 6 years of follow-up (SD = 2.8), the incidence rate of total strokes was 23.2/1,000 person-years for slow walkers compared to 15.6/1,000 person-years for medium walkers, and 7.6/1,000 person-years for fast walkers. In Cox models adjusted for sociodemographics, cardiovascular risk, cognition and functional status, and self-rated health, the hazard of total stroke was 31% lower for medium walkers (HR: 0.69, 95% confidence interval [CI]: 0.47, 1.02) and 56% lower for fast walkers (HR: 0.44, 95% CI: 0.24, 0.82) compared with slow walkers. We found similar associations with timed tandem walk ability (fully adjusted HR: 0.66, 95% CI: 0.45, 0.98). Conclusions: Our findings suggest perceived walking speed captures more than self-rated health alone and is a strong risk factor for stroke risk in Latino older adults. PMID- 27549993 TI - Greater body mass index is related to greater self-identified cold tolerance and greater insensible body mass loss. AB - BACKGROUND: Insensible body mass loss (IBL) from the human body continuously occurs, which is an important component in body heat exchange. The purpose of this study was to examine the relevance of IBL to anthropometric characteristics and self-identified thermal tolerance. METHODS: A total of 289 healthy young Korean males were chosen and sorted into the following three groups: heat tolerable only (HTO, N = 79), cold tolerable only (CTO, N = 104), neither heat nor cold tolerable (NHC, N = 106). They weighed before and after a 30-min rest under lightly clothed condition at an air temperature of 23 +/- 1 degrees C with a relative humidity 55 +/- 5 %RH. RESULTS: (1) The IBL of 289 males had a mean of 90 +/- 75 g h(-1) (48 +/- 40 g h(-1) m(-2)); (2) No significant difference in IBL among the three groups were found; (3) Significant differences in body weight and body mass index (BMI) among three groups were found (P < 0.05), but insignificance was found for height (P = 0.726) or body surface area (P = 0.059); (4) CTO was approximately 4.1 kg heavier in body weight (P < 0.05) and higher in BMI (P < 0.01) than in HTO; (5) Only for the group CTO, IBL (g h(-1)) showed a positive relationship to BMI (P < 0.05, R (2) = 0.056), but there was no relationship between IBL and body surface area. CONCLUSIONS: For healthy young males within normal anthropometric ranges in Korea, IBL was positively related to BMI, and individuals with greater BMI showed greater self-identified cold tolerance, but no direct relationship was found between IBL and self-identified cold tolerance. This suggests that body physique (e.g., BMI) could be an explanatory factor between insensible body heat loss and subjective cognition on cold tolerance. PMID- 27549994 TI - The 100th Anniversary of the American Board of Ophthalmology. AB - This is a special year for the American Board of Ophthalmology (ABO) as we celebrate 100 years of board certification. To mark this occasion, this supplement is being published, which provides an update on initial and continuous certification provided by the ABO. This editorial highlights a variety of changes in physician self-regulation through board certification. PMID- 27549995 TI - The American Academy of Ophthalmology and the Formation of the American Board of Ophthalmology. AB - At the turn of the 20th century, the American Academy of Ophthalmology and Otolaryngology joined the American Ophthalmological Society and the Section on Ophthalmology of the American Medical Association to form America's first board for the certification of medical specialists, the American Board of Ophthalmology. Academy leaders helped pave the way for the development of rigorous standards for the training of ophthalmologists and pushed for the advancement of excellence within the profession. PMID- 27549996 TI - The Evolution of the American Board of Ophthalmology Written Qualifying Examination. AB - Since the inception of board certification in ophthalmology in 1916, a written assessment of candidates' knowledge base has been an integral part of the certification process. Although the committee structure and technique for writing examination questions has evolved over the past 100 years, the written qualifying examination remains an essential tool for assessing the competency of physicians entering the workforce. To develop a fair and valid examination, the American Board of Ophthalmology builds examination questions using evidence-based, peer reviewed literature and adheres to accepted psychometric assessment standards. PMID- 27549997 TI - History of the American Board of Ophthalmology Oral Examination. AB - The oral examination has been an integral part of certification by the American Board of Ophthalmology (ABO) since its founding in 1916. An overview is provided regarding the history, evolution, and application of new technology for the oral examination. This part of the certifying process allows the ABO to assess candidates for a variety of competencies, including communication skills and professionalism. PMID- 27549998 TI - Excellence in Ophthalmology: Continuous Certification. AB - Over the course of a century, American medical specialty boards including the American Board of Ophthalmology (ABO) have developed significant expertise in assessing physician competence on completion of postgraduate training and, more recently, in defining appropriate criteria for continuous learning and quality improvement in practicing physicians. This article explores why maintaining career-long excellence is an evolving challenge, but one that is at the heart of the ABO's mission to protect the public by improving patient care. PMID- 27549999 TI - The History and Founding Organizations of the American Board of Ophthalmology. AB - In the early 1900s, ophthalmologists became the first group of American physicians to lead the call for the establishment of higher standards in the practice of medicine. This movement for excellence in practice evolved into a program of board certification through the creation of what is today the American Board of Ophthalmology (ABO). Three organizations-the American Ophthalmological Society, the Section on Ophthalmology of the American Medical Association, and the American Academy of Ophthalmology and Otolaryngology-are credited as the founders of the ABO. Representatives from these organizations were charged with overseeing the development of board certification programs from the ABO's inception in 1916 through 1982, when it became a fully autonomous organization. PMID- 27550000 TI - The Red Badge. AB - This article discusses the experience of progressing from a young ophthalmic resident to a full-time professional and, ultimately, to service on the American Board of Ophthalmology. PMID- 27550001 TI - A Century of Board Directors. AB - The selection of directors of the American Board of Ophthalmology (ABO) initially was carried out by the 3 founding organizations of the ABO: the American Medical Association, the American Ophthalmological Society, and the American Academy of Ophthalmology and Otolaryngology. Since 1982, the ABO has chosen its own directors and, in 2001, began adding public directors. It is only in recent years that women comprise an increasing proportion of ABO directors. PMID- 27550002 TI - The American Board of Ophthalmology Tie. AB - This article discusses the efforts of the American Board of Ophthalmology (ABO) to recognize and celebrate the contributions of its volunteers to certification programs and processes. In recognition of service to the ABO, all directors and examiners received ties for men and scarves for women bearing the ABO logo and colors. This article briefly describes the rationale and the importance of these articles for those who receive them. PMID- 27550003 TI - The History, Role, and Value of Public Directors on Certifying Boards: The American Board of Ophthalmology Experience. AB - The mission of the American Board of Ophthalmology (ABO) is to serve the public by improving the quality of ophthalmic practice through a continuing certification process that fosters excellence and encourages continual learning. Since 2001, achieving this mission has been enhanced by including public directors in the ABO governance. We review the evolution of including nonprofessional members on the governing boards of professional regulatory and self-regulatory organizations generally, provide history about the incorporation of non-professional public directors into the governance structure of the American Board of Medical Specialties and the ABO, and offer insights about the perceived impact of public directors on the ABO. PMID- 27550004 TI - Building a Culture of Safety in Ophthalmology. AB - Patient safety focused on a reduction in both procedural and diagnostic error is the number one concern of the United States healthcare system in the 21st century. The American Board of Ophthalmology has a longstanding interest in patient safety, and in 2015, teamed with the American Academy of Ophthalmology to convene all ophthalmology subspecialties and other prominent national organizations to address patient safety in ophthalmology. This article reviews the topic and highlights concerns for ophthalmologists. PMID- 27550005 TI - Measurement, Certification, and Quality: Meeting Enduring Challenges with Modern Tools. AB - The author, a former chair of the ABIM, describes the challenges that the board certification enterprise is experiencing as medicine shifts from being a paper based to a digital industry. While there are clearly threats to board certification, he argues that boards can remain highly relevant if they focus on areas in which they can make unique contributions, such as the measurement of cognitive skills, diagnostic accuracy, "keeping up," and procedural skills. PMID- 27550006 TI - Board Certification: The Global Perspective. AB - This article reviews globalization of quality standards in medicine, with emphasis on accreditation and certification. In conjunction with the 100th anniversary of the American Board of Ophthalmology, the author explores globalization movements, standards of quality, expectations of others seeking certification, the American Board of Medical Specialties (ABMS) International, interrelationships with the ABMS, and considerations both pragmatic and philosophical in addressing globalization of standards. PMID- 27550007 TI - Board Certification: Going Back to the Future. AB - The authors present snapshots of board certification in 1916, the year that the American Board of Ophthalmology was founded, 60 years later in 1976 as periodic recertification emerged, and speculation about what certification might look like in 2036. The concept of board certification and continuous certification in the medical specialties took shape at the beginning of the 20th century with the convergence of a new system of assessment, the emergence of certifying boards, and the creation of the American Board of Medical Specialties (ABMS). The importance of self-regulation is emphasized as are the principles underlying board certification and the standards that guide it to support its continued relevance as a valued credential and symbol of the highest standard in the practice of medicine. PMID- 27550008 TI - Creation of the American Board of Ophthalmology: The Role of the American Ophthalmological Society. AB - The American Ophthalmological Society (AOS) is 1 of the 3 founding organizations of the American Board of Ophthalmology (ABO), in addition to the Section on Ophthalmology of the American Medical Association and the American Academy of Ophthalmology and Otolaryngology. The early history of the AOS and its role in the founding of the ABO are addressed in this article. PMID- 27550010 TI - Profile: John Carwadine Pearson. PMID- 27550009 TI - Creation of the American Board of Ophthalmology: The Role of the American Medical Association. AB - In the early 20th century, the American Medical Association (AMA), specifically its Section on Ophthalmology, played a central role in the founding of America's first medical specialty board, the American Board of Ophthalmology. With the American Ophthalmological Society and the American Academy of Ophthalmology and Otolaryngology, the AMA's contributions to the formation of the American Board of Ophthalmology led to the establishment of sound educational standards for practicing ophthalmologists and helped to advance the culture of medical excellence within the profession that is synonymous with board certification today. PMID- 27550013 TI - Liver diseases: what is known so far about the therapy with human amniotic membrane? AB - Liver, the largest intern organ of the human body, is responsible for several vital tasks such as digestive and excretory functions, as well as for nutrients storage and metabolic functions, synthesis of new molecules and purification of toxic chemicals. Cirrhosis, fibrosis and hepatocellular carcinoma are the most prevalent liver diseases. Despite all the studies performed so far, treatment options for these diseases are very limited. For this reason, it is urgent to find effective therapies for these pathologies. Several studies have been performed during the last decade about the possible application of human amniotic membrane in hepatic diseases therapy. Promising results about human amniotic membrane or its derived cells, in vitro and in vivo, applications in fibrosis, cirrhosis and hepatocellular carcinoma were already published. Since it is an attractive study area, it is becoming a dynamic scientific subject. However, the action mechanisms of human amniotic membrane and its derived cells in hepatic diseases therapy must be precisely known in order that this promising therapy could be clinically used. PMID- 27550014 TI - Novel 3D scaffold with enhanced physical and cell response properties for bone tissue regeneration, fabricated by patterned electrospinning/electrospraying. AB - Developing three dimensional scaffolds mimicking the nanoscale structure of native extracellular matrix is a key parameter in tissue regeneration. In this study, we aimed to introduce a novel 3D structures composed of nanofibers (NF) and micro particles (MP) and compare their efficiency with 2D nanofibrous scaffold. The conventional nanofibrous PCL scaffolds are 2D mats fabricated by the electrospinning technique, whereas the NF/MP and patterned NF/MP PCL scaffolds are three dimensional structures fabricated by a modified electrospinning/electrospraying technique. The mentioned method was carried out by varying the electrospinning solution parameters and use of a metal mesh as the collector. Detailed fabrication process and morphological properties of the fabricated structures is discussed and porosity, pore size and PBS solution absorption value of the prepared structures are reported. Compared with the 2D structure, 3D scaffolds possessed enhanced porosity and pore size which led to the significant increase in their water uptake capacity. In vitro cell experiments were carried out on the prepared structures by the use of MG-63 osteosarcoma cell line. The fabricated 3D structures offered significantly increased cell attachment, spread and diffusion which were confirmed by SEM analysis. In vitro cytocompatibility assessed by MTT colorimetric assay indicated a continuous cell proliferation over 21 days on the innovative 3D structure, while on 2D mat cell proliferation stopped at early time points. Enhanced osteogenic differentiation of the seeded MG-63 cells on 3D scaffold was confirmed by the remarkable ALP activity together with increased and accelerated calcium deposition on this structure compared to 2D mat. Massive and well distributed bone minerals formed on patterned 3D structure were shown by EDX analysis. In comparison between NF/MP quasi-3D and Patterned NF/MP 3D scaffolds, patterned structures proceeded in all of the above properties. As such, the innovative Patterned NF/MP 3D scaffold could be considered as a proper bone graft substitute for bone tissue regeneration. PMID- 27550016 TI - Miniaturized soft bio-hybrid robotics: a step forward into healthcare applications. AB - Soft robotics is an emerging discipline that employs soft flexible materials such as fluids, gels and elastomers in order to enhance the use of robotics in healthcare applications. Compared to their rigid counterparts, soft robotic systems have flexible and rheological properties that are closely related to biological systems, thus allowing the development of adaptive and flexible interactions with complex dynamic environments. With new technologies arising in bioengineering, the integration of living cells into soft robotic systems offers the possibility of accomplishing multiple complex functions such as sensing and actuating upon external stimuli. These emerging bio-hybrid systems are showing promising outcomes and opening up new avenues in the field of soft robotics for applications in healthcare and other fields. PMID- 27550015 TI - Resting-state test-retest reliability of a priori defined canonical networks over different preprocessing steps. AB - Resting-state functional connectivity analysis has become a widely used method for the investigation of human brain connectivity and pathology. The measurement of neuronal activity by functional MRI, however, is impeded by various nuisance signals that reduce the stability of functional connectivity. Several methods exist to address this predicament, but little consensus has yet been reached on the most appropriate approach. Given the crucial importance of reliability for the development of clinical applications, we here investigated the effect of various confound removal approaches on the test-retest reliability of functional connectivity estimates in two previously defined functional brain networks. Our results showed that gray matter masking improved the reliability of connectivity estimates, whereas denoising based on principal components analysis reduced it. We additionally observed that refraining from using any correction for global signals provided the best test-retest reliability, but failed to reproduce anti correlations between what have been previously described as antagonistic networks. This suggests that improved reliability can come at the expense of potentially poorer biological validity. Consistent with this, we observed that reliability was proportional to the retained variance, which presumably included structured noise, such as reliable nuisance signals (for instance, noise induced by cardiac processes). We conclude that compromises are necessary between maximizing test-retest reliability and removing variance that may be attributable to non-neuronal sources. PMID- 27550017 TI - Aqueous extract from the Withania somnifera leaves as a potential anti neuroinflammatory agent: a mechanistic study. AB - BACKGROUND: Microglial-mediated neuroinflammation is a key factor underlying the pathogenesis of various neurodegenerative diseases and also an important target for the development of the neuroinflammation-targeted therapeutics. Conventionally, the nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed, but they are associated with long-term potential risks. Natural products are the cornerstone of modern therapeutics, and Ashwagandha is one such plant which is well known for its immunomodulatory properties in Ayurveda. METHODS: The current study was aimed to investigate the anti-neuroinflammatory potential of Ashwagandha (Withania somnifera) leaf water extract (ASH-WEX) and one of its active chloroform fraction (fraction IV (FIV)) using beta-amyloid and lipopolysaccharide (LPS)-stimulated primary microglial cells and BV-2 microglial cell line. Iba-1 and alpha-tubulin immunocytochemistry was done to study the LPS- and beta-amyloid-induced morphological changes in microglial cells. Inflammatory molecules (NFkB, AP1), oxidative stress proteins (HSP 70, mortalin), apoptotic markers (Bcl-xl, PARP), cell cycle regulatory proteins (PCNA, Cyclin D1), and MHC II expression were analyzed by Western blotting. Mitotracker and CellRox Staining, Sandwich ELISA, and Gelatin Zymography were done to investigate ROS, pro-inflammatory cytokines, and matrix metalloproteinase production, respectively. Ashwagandha effect on microglial proliferation, migration, and its apoptosis-inducing potential was studied by cell cycle analysis, migration assay, and Annexin-V FITC assay, respectively. RESULTS: ASH-WEX and FIV pretreatment was seen to suppress the proliferation of activated microglia by causing cell cycle arrest at Go/G1 and G2/M phase along with decrease in cell cycle regulatory protein expression such as PCNA and Cyclin D1. Inhibition of microglial activation was revealed by their morphology and downregulated expression of microglial activation markers like MHC II and Iba-1. Both the extracts attenuated the TNF-alpha, IL-1beta, IL-6, RNS, and ROS production via downregulating the expression of inflammatory proteins like NFkB and AP1. ASH-WEX and FIV also restricted the migration of activated microglia by downregulating metalloproteinase expression. Controlled proliferation rate was also accompanied by apoptosis of activated microglia. ASH-WEX and FIV were screened and found to possess Withaferin A and Withanone as active phytochemicals. CONCLUSIONS: The current data suggests that ASH-WEX and FIV inhibit microglial activation and migration and may prove to be a potential therapeutic candidate for the suppression of neuroinflammation in the treatment of neurodegenerative diseases. PMID- 27550019 TI - Do marginalized neighbourhoods have less healthy retail food environments? An analysis using Bayesian spatial latent factor and hurdle models. AB - BACKGROUND: Findings of whether marginalized neighbourhoods have less healthy retail food environments (RFE) are mixed across countries, in part because inconsistent approaches have been used to characterize RFE 'healthfulness' and marginalization, and researchers have used non-spatial statistical methods to respond to this ultimately spatial issue. METHODS: This study uses in-store features to categorize healthy and less healthy food outlets. Bayesian spatial hierarchical models are applied to explore the association between marginalization dimensions and RFE healthfulness (i.e., relative healthy food access that modelled via a probability distribution) at various geographical scales. Marginalization dimensions are derived from a spatial latent factor model. Zero-inflation occurring at the walkable-distance scale is accounted for with a spatial hurdle model. RESULTS: Neighbourhoods with higher residential instability, material deprivation, and population density are more likely to have access to healthy food outlets within a walkable distance from a binary 'have' or 'not have' access perspective. At the walkable distance scale however, materially deprived neighbourhoods are found to have less healthy RFE (lower relative healthy food access). CONCLUSION: Food intervention programs should be developed for striking the balance between healthy and less healthy food access in the study region as well as improving opportunities for residents to buy and consume foods consistent with dietary recommendations. PMID- 27550020 TI - The problematic use of Information and Communication Technologies (ICT) in adolescents by the cross sectional JOITIC study. AB - BACKGROUND: The emerging field of Information and Communications Technology (ICT) has brought about new interaction styles. Its excessive use may lead to addictive behaviours. The objective is to determine the prevalence of the problematic use of ICT such as Internet, mobile phones and video games, among adolescents enrolled in mandatory Secondary Education (ESO in Spanish) and to examine associated factors. METHODS: Cross sectional, multi-centric descriptive study. POPULATION: 5538 students enrolled in years one to four of ESO at 28 schools in the Valles Occidental region (Barcelona, Spain). DATA COLLECTION: self administered socio-demographic and ICT access questionnaire, and validated questionnaires on experiences related to the use of the Internet, mobile phones and video games (CERI, CERM, CERV). RESULTS: Questionnaires were collected from 5,538 adolescents between the ages of 12 and 20 (77.3 % of the total response), 48.6 % were females. Problematic use of the Internet was observed in 13.6 % of the surveyed individuals; problematic use of mobile phones in 2.4 % and problematic use in video games in 6.2 %. Problematic Internet use was associated with female students, tobacco consumption, a background of binge drinking, the use of cannabis or other drugs, poor academic performance, poor family relationships and an intensive use of the computer. Factors associated with the problematic use of mobile phones were the consumption of other drugs and an intensive use of these devices. Frequent problems with video game use have been associated with male students, the consumption of other drugs, poor academic performance, poor family relationships and an intensive use of these games. CONCLUSIONS: This study offers information on the prevalence of addictive behaviours of the Internet, mobile phones and video game use. The problematic use of these ICT devices has been related to the consumption of drugs, poor academic performance and poor family relationships. This intensive use may constitute a risk marker for ICT addiction. PMID- 27550021 TI - The Absorb bioresorbable vascular scaffold for the treatment of coronary artery disease. AB - INTRODUCTION: Every decade the field of interventional cardiology is revolutionized by new technology. The fully bioresorbable everolimus-eluting scaffold (ABSORB BVS) technology would preserve the benefits of metallic stents by sealing balloon-induced dissections, avoiding elastic recoil and vessel occlusion. The polymeric scaffold would be resorbed to restore the natural integrity of the vessel, superseding the consequence of the permanent presence of a foreign body in the coronary artery. AREAS COVERED: This technology evaluation focuses on the clinical evidence for the use of bioresorbable everolimus-eluting scaffold for the treatment of coronary artery disease. EXPERT OPINION: The current generation of the bioresorbable scaffold has structural and mechanical limitations that might preclude the widespread use in clinical practice. The strut thickness (150 um) limits deliverability and creates laminar flow disruptions that might be the nidus of an increased rate of scaffold thrombosis. In the next generation of bioresorbable scaffolds, the resorption process should be faster and in particular, strut thickness must be reduced. This will probably represent a significant step forward in an attempt to increase the efficacy and safety profile of the device and achieve a similar performance with the current generation drug-eluting stent even in complex scenarios. PMID- 27550023 TI - Fewer people are quitting smoking, say NHS stop smoking services. PMID- 27550022 TI - The effect of patient anxiety and depression on motion during myocardial perfusion SPECT imaging. AB - BACKGROUND: Patient motion during myocardial perfusion SPECT imaging (MPI) may be triggered by a patient's physical and/or psychological discomfort. The aim of this study was to investigate the impact of state anxiety (patient's reaction to exam-related stress), trait anxiety (patient's personality characteristic) and depression on patient motion during MPI. METHODS: All patients that underwent MPI in our department in a six-month period were prospectively enrolled. One hundred eighty-three patients (45 females; 138 males) filled in the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI), along with a short questionnaire regarding their age, height and weight, level of education in years, occupation, and marital status. Cardiovascular and other co-morbidity factors were also evaluated. Through inspection of raw data on cinematic display, the presence or absence of patient motion was registered and classified into mild, moderate and severe, for both phases involved in image acquisition. RESULTS: The correlation of patient motion in the stress and delay phases of MPI and each of the other variables was investigated and the corresponding Pearson's coefficients of association were calculated. The anxiety-motion (r = 0.43, P < 0.0001) and depression-motion (r = 0.32, P < 0.0001) correlation results were moderately strong and statistically significant for the female but not the male patients. All the other variables did not demonstrate any association with motion in MPI, except a weak correlation between age and motion in females (r = 0.23, P < 0.001). CONCLUSIONS: The relationship between anxiety-motion and depression motion identified in female patients represents the first supporting evidence of psychological discomfort as predisposing factor for patient motion during MPI. PMID- 27550040 TI - Which level is responsible for gluteal pain in lumbar disc hernia? AB - BACKGROUND: There are many different reasons why patients could be experiencing pain in the gluteal area. Previous studies have shown an association between radicular low back pain (LBP) and gluteal pain (GP). Studies locating the specific level responsible for gluteal pain in lumbar disc hernias have rarely been reported. METHODS: All patients with lumbar disc herniation (LDH) in the Kanghua hospital from 2010 to 2014 were recruited. All patients underwent a lumbar spine MRI to clarify their LDH diagnosis, and patients were allocated to a GP group and a non-GP group. To determine the cause and effect relationship between LDH and GP, all of the patients were subjected to percutaneous endoscopic lumbar discectomy (PELD). RESULTS: A total of 286 cases were included according to the inclusive criteria, with 168 cases in the GP group and 118 cases in the non-GP group. Of these, in the GP group, 159 cases involved the L4/5 level and 9 cases involved the L5/S1 level, while in the non-GP group, 43 cases involved the L4/5 level and 48 cases involved the L5/S1 level. PELD was performed in both groups. Gluteal pain gradually disappeared after surgery in all of the patients. Gluteal pain recrudesced in a patient with recurrent disc herniation (L4/5). CONCLUSIONS: As a clinical finding, gluteal pain is related to low lumbar disc hernia. The L4/5 level is the main level responsible for gluteal pain in lumbar disc hernia. No patients with gluteal pain exhibited involvement at the L3/4 level. PMID- 27550041 TI - Site-specific glycosylation of donkey milk lactoferrin investigated by high resolution mass spectrometry. AB - A comprehensive monosaccharide composition of the N-glycans of donkey milk lactoferrin, isolated by ion exchange chromatography from an individual milk sample, was obtained by means of chymotryptic digestion, TiO2 and HILIC enrichment, reversed-phase high-performance liquid chromatography, electrospray mass spectrometry, and high collision dissociation fragmentation. The results obtained allowed identifying 26 different glycan structures, including high mannose, complex and hybrid N-glycans, linked to the protein backbone via an amide bond to asparagine residues located at the positions 137, 281 and 476. Altogether, the N-glycan structures determined revealed that most of the N glycans identified in donkey milk lactoferrin are neutral complex/hybrid. Indeed, 10 neutral non-fucosylated complex/hybrid N-glycans and 4 neutral fucosylated complex/hybrid N-glycans were found. In addition, two high mannose N-glycans, four sialylated fucosylated complex N-glycans and six sialylated non-fucosylated complex N-glycans, one of which containing N-glycolylneuraminic acid (Neu5Gc), were found. A comparison of the monosaccharide composition of the N-glycans of donkey milk lactoferrin with respect to that of human, bovine and goat milk lactoferrin is reported. Data are available via ProteomeXchange with identifier PXD004289. PMID- 27550043 TI - Spinal nerve defects in mouse embryos prenatally exposed to valproic acid. AB - To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day 8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6-10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects. Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells, which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence would be useful to examine the effects of valproic acid on the somitogenesis and morphogenesis of somite-associated structures. PMID- 27550042 TI - Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations. AB - BACKGROUND: A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through in silico studies. RESULTS: To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use. CONCLUSIONS: Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome, i.e., extinction of sensitive cells and selection of highly resistant cells. Also, our mathematical results formalise the idea that the use of cytotoxic agents at high doses can act as a double-edged sword by promoting the outgrowth of drug resistant cellular clones. Overall, our theoretical work offers a formal basis for the development of anti-cancer therapeutic protocols that go beyond the 'maximum-tolerated-dose paradigm', as they may be more effective than traditional protocols at keeping the size of cancer cell populations under control while avoiding the expansion of drug tolerant clones. REVIEWERS: This article was reviewed by Angela Pisco, Sebastien Benzekry and Heiko Enderling. PMID- 27550044 TI - Health Promotion Board-Ministry of Health Clinical Practice Guidelines: Obesity. PMID- 27550045 TI - [Infected osteosynthesis]. AB - BACKGROUND: Infections after osteosynthesis are a feared complication of the surgical treatment of fractures and should be dealt with by a multidisciplinary team. In addition to the surgeon, also included in this multidisciplinary team are a specialist for infectious diseases, a microbiologist, a radiologist and often a plastic surgeon. This review article describes the current knowledge on the pathogenesis, diagnostics, classification and treatment. The aim is to demonstrate some basic rules in the treatment of infections associated with implants and to show potential therpeutic approaches. MATERIAL AND METHODS: The principles of diagnostics and combined surgical and antibiotic treatment are presented based on the current specialist literature. RESULTS: With the help of a team approach the goals of treatment of an infected osteosynthesis, i.e. fracture healing, return to function and eradication of infection can be achieved. While the osteosynthesis material can usually be retained in acute infections, it is better to remove the infected hardware in chronic infections as eradication of the mature biofilm is no longer possible. DISCUSSION: With adequate local wound debridement, the use of local and systemic antibiotics, as indicated by the specialist for infectious diseases and appropriate soft tissue coverage and wound closure, acute as well as chronic infections can be successfully treated. Nowadays, the surgeon has many different options for the management of bone defects. Depending on the anatomical location and the size of the defect a variety of techniques ranging from acute shortening to the Masquelet technique up to the Ilizarov distraction technique are available. These techniques should be combined with local bactericidal treatment. PMID- 27550046 TI - A Rare Case of Angioleiomyoma Arising in the Subglottic Area to Upper Trachea of a Patient with Underlying Asthma. AB - Angioleiomyoma is a rare disease that is histologically characterized by smooth muscle cells arranged around vascular spaces. Although angioleiomyomas occur rarely in the head and neck region, they can cause various symptoms according the site involved. Here, we present a 44-year-old male patient with a 15-year history of asthma, who presented with recent onset of chest discomfort, globus sensation and throat pain. Medication was not effective in relieving his symptoms, and further evaluation revealed a polypoid ovoid mass, almost obstructing the airway at the border of the larynx and upper trachea on chest computed tomography. The mass was completely resected via a rigid bronchoscopy procedure. Histopathologic examination revealed that the excised mass was angioleiomyoma, which was immunohistochemically positive for smooth muscle actin and negative for desmin. PMID- 27550047 TI - Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation. AB - BACKGROUND: A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B cell lymphomas (DLBCLs). METHODS: The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs. RESULTS: The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression. CONCLUSIONS: HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome. PMID- 27550048 TI - Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma. AB - BACKGROUND: There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. METHODS: We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. RESULTS: From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. CONCLUSIONS: Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma. PMID- 27550049 TI - A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome. AB - We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1-7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations. PMID- 27550050 TI - Influence of Ultraviolet/Ozonolysis Treatment of Nanocarbon Filler on the Electrical Resistivity of Epoxy Composites. AB - In the present work, we have investigated concentration and temperature dependences of electrical conductivity of graphite nanoplatelets/epoxy resin composites. The content of nanocarbon filler is varied from 0.01 to 0.05 volume fraction. Before incorporation into the epoxy resin, the graphite nanoplatelets were subjected to ultraviolet ozone treatment at 20-min ultraviolet exposure. The electric resistance of the samples was measured by two- or four-probe method and teraohmmeter E6-13. Several characterization techniques were employed to identify the mechanisms behind the improvements in the electrical properties, including SEM and FTIR spectrum analysis.It is established that the changes of the relative intensities of the bands in FTIR spectra indicate the destruction of the carboxyl group -COOH and group -OH. Electrical conductivity of composites has percolation character and graphite nanoplatelets (ultraviolet ozone treatment for 20 min) addition which leads to a decrease of percolation threshold 0.005 volume fraction and increase values of electrical conductivity (by 2-3 orders of magnitude) above the percolation threshold in comparison with composite materials-graphite nanoplatelets/epoxy resin. The changes of the value and behavior of temperature dependences of the electrical resistivity of epoxy composites with ultraviolet/ozone-treated graphite nanoparticles have been analyzed within the model of effective electrical conductivity. The model takes into account the own electrical conductivity of the filler and the value of contact electric resistance between the filler particles of the formation of continuous conductive pathways. PMID- 27550051 TI - Electronic Structures of Silicene Nanoribbons: Two-Edge-Chemistry Modification and First-Principles Study. AB - In this paper, we investigate the structural and electronic properties of zigzag silicene nanoribbons (ZSiNRs) with edge-chemistry modified by H, F, OH, and O, using the ab initio density functional theory method and local spin-density approximation. Three kinds of spin polarized configurations are considered: nonspin polarization (NM), ferromagnetic spin coupling for all electrons (FM), ferromagnetic ordering along each edge, and antiparallel spin orientation between the two edges (AFM). The H, F, and OH groups modified 8-ZSiNRs have the AFM ground state. The directly edge oxidized (O1) ZSiNRs yield the same energy and band structure for NM, FM, and AFM configurations, owning to the same s p (2) hybridization. And replacing the Si atoms on the two edges with O atoms (O2) yields FM ground state. The edge-chemistry-modified ZSiNRs all exhibit metallic band structures. And the modifications introduce special edge state strongly localized at the Si atoms in the edge, except for the O1 form. The modification of the zigzag edges of silicene nanoribbons is a key issue to apply the silicene into the field effect transistors (FETs) and gives more necessity to better understand the experimental findings. PMID- 27550052 TI - Sustained, Controlled and Stimuli-Responsive Drug Release Systems Based on Nanoporous Anodic Alumina with Layer-by-Layer Polyelectrolyte. AB - Controlled drug delivery systems are an encouraging solution to some drug disadvantages such as reduced solubility, deprived biodistribution, tissue damage, fast breakdown of the drug, cytotoxicity, or side effects. Self-ordered nanoporous anodic alumina is an auspicious material for drug delivery due to its biocompatibility, stability, and controllable pore geometry. Its use in drug delivery applications has been explored in several fields, including therapeutic devices for bone and dental tissue engineering, coronary stent implants, and carriers for transplanted cells. In this work, we have created and analyzed a stimuli-responsive drug delivery system based on layer-by-layer pH-responsive polyelectrolyte and nanoporous anodic alumina. The results demonstrate that it is possible to control the drug release using a polyelectrolyte multilayer coating that will act as a gate. PMID- 27550053 TI - Beta-Blockers are Associated with Decreased In-Hospital Mortality and Stroke in Acute Decompensated Heart Failure: Findings from a Retrospective Analysis of a 22 Year Registry in the Middle East (1991-2013). AB - BACKGROUND: Beta-blockers reduce mortality in chronic heart failure. OBJECTIVES: To study intra-hospital mortality and adverse cardiovascular (CV) outcomes in relation to beta-blockade therapy in acute decompensated heart failure. METHODS: We retrospectively analyzed a 22-year registry of acute decompensated heart failure (ADHF) in the Middle East. RESULTS: Out of the total 8066 patients admitted for ADHF, 1242(15.4%) were on beta-blockers on admission. Among those, beta-blockers were discontinued in 26.5%. Despite the existence of less CV comorbidities in patients not treated by beta-blockers, in-hospital mortality and stroke/transient ischemic attacks rates were higher in those patients compared with patients on beta-blockers on admission (14.4 vs. 3.6%, p=0.001, 0.6 vs. 0.1%, p=0.02; respectively). Additionally, continuation of beta-blockers during acute decompensation was associated with less mortality risk (p=0.001). The use of beta-blockers on admission and discharge increased significantly with time whereas in-hospital mortality decreased (p=0.001). Nevertheless, admission year was not a predictor of reduced mortality in patients treated with beta-blockers on admission (OR 0.93, 95% CI [0.56-1.54], p=0.77). CONCLUSION: Previous beta blockade therapy in patients presenting with ADHF decreases intra-hospital mortality and the incidence of CV events and stroke/transient ischemic attacks. Moreover, nonwithdrawal of beta-blockers during hospitalization has a favorable outcome. PMID- 27550054 TI - Type 2 Diabetes Mellitus and the Elderly: An Update on Drugs Used to Treat Glycaemia. AB - Type 2 Diabetes Mellitus (T2DM) and its complications are more prevalent in the elderly. As the general population worldwide is ageing, effective and safe treatment of older T2DM patients is becoming more important in clinical practice. Elderly T2DM patients should be carefully evaluated for functional, mental, geriatric and medical disorders before the initiation of antidiabetic drug therapy and regularly monitored thereafter. Treatment strategy and goals should be individualized based on patient comorbidities and drug pharmacokinetic and pharmacodynamic properties. This narrative review discusses the use of antidiabetic drugs in the elderly T2DM population. PMID- 27550056 TI - Transition in Infant and Young Child Feeding Practices in India. AB - INTRODUCTION: Optimal infant and young child feeding, which includes initiation of breastfeeding within one hour of birth, exclusive breastfeeding for first six months, age appropriate complementary feeding after six months along with continued breastfeeding for 2 years and beyond, is a public health intervention to prevent child morbidity, mortality and malnutrition [1]. In India, even though institutional delivery rates are increasing, only 44% women are able to breastfeed their babies within one hour of delivery. While 65% children are exclusively breast fed for the first six months, the median duration of breastfeeding is 24.4 months and complementary feeding rates are 50%. To achieve optimal IYCF practices, each woman should have access to a community based IYCF counseling support system. Efforts are therefore needed to upgrade skill based training of health workers and revive and update the Baby Friendly Hospital Initiative (BFHI). To promote and sustain breastfeeding amongst working women, it is essential to ensure adequate maternity leave, creches at work place, flexible working hours, and provision of physical space for breast feeding at work place. It is imperative to also create public awareness about the dangers of bottle and formula feeding and to provide accurate information on the appropriate complementary food to be given to infants. CONCLUSION: In conclusion, India needs to make serious efforts to overcome malnutrition with not only prioritized IYCF policies but also their effective implementation in place. PMID- 27550055 TI - Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus? AB - OBJECTIVE: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients. PATIENTS AND METHODS: 353 patients with diabetes (DM) were recruited (age: 60.2+/-7.4 years; female: 57.2%; BMI: 29.3+/-2.1 kg/m2; DM duration: 15.6+/-9.9 years; HbA1c: 7.8+/-1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test. RESULTS: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (y=0.004, p=0.563), 30/15 ratio (y=0.282, p=0.357), Valsalva ratio (y=-0.058, p=0.436) and orthostatic hypotension (y=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006). CONCLUSION: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM associated complications by initiating early treatment. PMID- 27550057 TI - Evaluation of the immunomodulatory effects of a South African commercial traditional immune booster in human peripheral blood mononuclear cells. AB - BACKGROUND: With the burden of HIV and AIDS still very high, South Africa has seen an increase in commercial traditional medicines claiming to have immune enhancing effects. Because of lack of regulation of the traditional medicine sector, these products have proliferated. This study aimed to evaluate the immunomodulatory effects of uMakhonya(r), a commercial traditional immune booster, using various models of normal human peripheral blood mononuclear cells (PBMCs). METHODS: Immunosuppressed, mitogen-, and peptidoglycan (PG)-stimulated PBMCs were treated with various doses of uMakhonya(r) and incubated for 24 h. The treated and control samples were analyzed for cytotoxicity, secretion of 12 different inflammatory cytokines, soluble interleukin-2 receptor (sIL-2R) levels, and nitric oxide (NO) secretion. RESULTS: In cytotoxicity assays, uMakhonya(r) induced dose-dependent cytotoxic effects in all three models, with IC50 values of 512.08, 500, and 487.91 MUg/mL for immunosuppressed, phytohaemagglutinin (PHA)-, and PG from Staphylococcus. aureus (PG-S. aureus)-stimulated PBMCs, respectively. UMakhonya(r) at 100 and 10 MUg/mL induced a significant (p < 0.05) increase in the secretion of IL-1alpha, IL-1beta, IL-6, IL-10, tumor necrosis factor alpha (TNF)-alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in cyclosporine-, immunosuppressed, and PHA-stimulated PBMCs. In the same samples, there was a significant increase (p < 0.05) in sIL-2R concentration, which correlated with an increase in the secretion of inflammatory cytokines. In PBMCs stimulated with PG-S. aureus, uMakhonya(r) at doses of 100 and 10 MUg/mL significantly (p < 0.05) suppressed the secretion of inflammatory cytokines, especially IL-1beta and TNF-alpha. PG-S. aureus-stimulated PBMCs also showed a significant decrease (p < 0.05) in sIL-2R concentration when compared to control samples. UMakhonya(r) insignificantly (p > 0.05) decreased NO levels in PBMCs after PG-S. aureus stimulation. CONCLUSIONS: These results showed that uMakhonya(r) can induce both pro-inflammatory and anti-inflammatory effects depending on the initial stimuli applied to immune cells. PMID- 27550058 TI - Implant survival of the most common cemented total hip devices from the Nordic Arthroplasty Register Association database. AB - Background and purpose - According to previous Nordic Arthroplasty Register Association (NARA) data, the 10-year implant survival of cemented total hip arthroplasties (THAs) is 94% in patients aged 65-74 and 96% in patients aged 75 or more. Here we report a brand-level comparison of cemented THA based on the NARA database, which has not been done previously. Patients and methods - We determined the rate of implant survival of the 9 most common cemented THAs in the NARA database. We used Kaplan-Meier analysis with 95% CI to study implant survival at 10 and 15 years, and Cox multiple regression to assess survival and hazard ratios (HRs), with revision for any reason as endpoint and with adjustment for age, sex, diagnosis, and femoral head material. Results - Spectron EF THA (89.9% (CI: 89.3-90.5)) and Elite THA (89.8% (CI: 89.0-90.6)) had the lowest 10 year survivorship. Lubinus (95.7% survival, CI: 95.5-95.9), MS 30 (96.6%, CI: 95.8-97.4), and C-stem THA (95.8%, CI: 94.8-96.8) had a 10-year survivorship of at least 95%. Lubinus (revision risk (RR) = 0.77, CI: 0.73-0.81), Muller (RR =0.83, CI: 0.70-0.99), MS-30 (RR =0.73, CI: 0.63-0.86), C-stem (RR =0.70, CI: 0.55-0.90), and Exeter Duration THA (RR =0.84, CI: 0.77-0.90) had a lower risk of revision than Charnley THA, the reference implant. Interpretation - The Spectron EF THA and the Elite THA had a lower implant survival than the Charnley, Exeter, and Lubinus THAs. Implant survival of the Muller, MS 30, CPT, and C-stem THAs was above the acceptable limit for 10-year survival. PMID- 27550059 TI - Predictive model for early math skills based on structural equations. AB - Early math skills are determined by higher cognitive processes that are particularly important for acquiring and developing skills during a child's early education. Such processes could be a critical target for identifying students at risk for math learning difficulties. Few studies have considered the use of a structural equation method to rationalize these relations. Participating in this study were 207 preschool students ages 59 to 72 months, 108 boys and 99 girls. Performance with respect to early math skills, early literacy, general intelligence, working memory, and short-term memory was assessed. A structural equation model explaining 64.3% of the variance in early math skills was applied. Early literacy exhibited the highest statistical significance (beta = 0.443, p < 0.05), followed by intelligence (beta = 0.286, p < 0.05), working memory (beta = 0.220, p < 0.05), and short-term memory (beta = 0.213, p < 0.05). Correlations between the independent variables were also significant (p < 0.05). According to the results, cognitive variables should be included in remedial intervention programs. PMID- 27550060 TI - Effectiveness of golimumab for rheumatoid arthritis in patients with an inadequate response to tocilizumab. AB - OBJECTIVES: Several biological disease-modifying antirheumatic drugs (bDMARDs) are currently available for the treatment of rheumatoid arthritis (RA). Increasing evidence indicates that second-line bDMARDs are effective for inadequate responders to first-line bDMARDs. However, all previous studies investigated the use of tumor necrosis factor inhibitors (TNFi) as a first-line bDMARD, while investigated the efficacy of second-line bDMARDs after the use of tocilizumab (TCZ), a non-TNFi, as a first-line bDMARD. Thus, we investigated the efficacy of golimumab (GLM) as a second-line bDMARD after treatment with TCZ as a first-line bDMARD. METHODS: The final study population consisted of 26 patients (inadequate responders to TCZ; TCZ group) with moderate or high disease activity (DAS28-ESR >=3.2) at week 24 of treatment with TCZ as a first-line bDMARD or whose DAS28-ESR score worsened after starting TCZ treatment. These patients could be followed for another 52 weeks or more after the subsequent switch to GLM treatment. For comparison, 19 patients treated with TNFi as a first-line bDMARD and inadequate response to TNFi (TNFi group) were included. RESULTS: The DAS28 ESR score at week 52 after the start of treatment with GLM improved significantly compared with baseline in the TCZ and TNFi groups. However, the TCZ group showed significantly better improvement. Patients in both groups had significantly improved treatment outcomes according to European League Against Rheumatism response criteria, but there was no statistically significant difference among them. The retention rate at week 52 after the start of treatment with GLM was significantly higher in the TCZ group than in the TNFi group (81% vs. 68%, respectively). In addition, no difference was found in the progression of bone destruction determined by the change in van der Heijde modified total Sharp scoring system scores between groups. CONCLUSIONS: GLM was an effective therapeutic option for inadequate responders to TCZ. PMID- 27550061 TI - Baby Boomers and the Long-Term Transformation of Retirement and Volunteering: Evidence for a Policy Paradigm Shift. AB - In this article, we analyze two predictions about baby boomers that have contributed to the current policy paradigm: that the boomers will reinvent retirement, and that they have the potential to engage in higher levels of formal volunteering than previous generations. Empirical evidence from various studies and surveys do not support this paradigm. In fact, the data lead to the conclusion that baby boomers are neither initiating the reinvention of retirement, nor are they the initiators of a surge in volunteerism. Instead, they are part of an ongoing evolution of retirement and volunteerism begun by their parents' generation. We propose several assumptions to construct an alternative policy paradigm: Baby boomers need to be recognized as a diverse age cohort whose engagement is multi-faceted. Volunteer recruitment and oversight require creative approaches which focus on the communal and membership aspects of volunteering rather than focusing on volunteering as unpaid "work." PMID- 27550062 TI - Understanding Hearing Loss and Barriers to Hearing Health Care Among Korean American Older Adults: A Focus Group Study. AB - Hearing loss is associated with an accelerated decline in social, cognitive, and physical functioning among older adults. However, little is known about its impact and barriers to hearing health care in any ethnic minorities. The aim of this study was to explore experiences related to hearing loss and barriers to hearing health care among older Korean Americans (KAs). We conducted four focus groups with 19 older KAs with hearing loss and four communication partners. Qualitative content analysis revealed four themes: (a) impact of hearing loss, (b) self-perception of hearing loss, (c) coping strategies for hearing loss, and (d) barriers to hearing health care (price, language, lack of collaborative communications, perceptions about hearing aids, and lack of knowledge). Older KAs were significantly impacted by hearing loss but tended not to seek care due to multiple factors. Culturally tailored hearing interventions are urgently needed to promote hearing health in the KA community. PMID- 27550063 TI - Palladium-Assisted Cleavage of Peptides and Proteins Containing a Backbone with Thiazolidine Linkage. AB - The design and synthesis of biomolecules that are responsive to external stimuli is of great interest in various research areas, such as in the preparation of smart biomaterial and chemical biology. Polypeptide backbone disassembly as a response to a particular stimulus is of interest, as it leads to a complete loss of the protein tertiary structure and, as a result, to a loss of function. In this study, a strategy based on palladium-assisted efficient cleavage of backbone thiazolidine linkage in peptides and proteins was developed. Using a fluorescence based assay, encompassing ubiquitinated peptide with a quenching florescence pair, it was possible to optimize the cleavage step after rapid screening of various conditions, such as the type of metal complexes and reaction additives. The optimized conditions prompted fast cleavage of the thiazolidine linkage. The straightforward introduction of a backbone thiazolidine linkage in peptide and proteins coupled with the chemical methods used offers new opportunities in controlling macromolecule function and might, with the aid of cellular protein delivery methods, be applied in cellular settings. PMID- 27550066 TI - Can curative antivirals benefit porphyria cutanea tarda in hepatitis C patients? PMID- 27550064 TI - Charge and spin transport in single and packed ruthenium-terpyridine molecular devices: Insight from first-principles calculations. AB - Using first-principles calculations, we study the electronic and transport properties of rutheniumterpyridine molecules sandwiched between two Au(111) electrodes. We analyse both single and packed molecular devices, more amenable to scaling and realistic integration approaches. The devices display all together robust negative differential resistance features at low bias voltages. Remarkably, the electrical control of the spin transport in the studied systems implies a subtle distribution of the magnetisation density within the biased devices and highlights the key role of the Au(111) electrical contacts. PMID- 27550065 TI - Expression and Role of PAICS, a De Novo Purine Biosynthetic Gene in Prostate Cancer. AB - BACKGROUND: Our goal was to investigate de novo purine biosynthetic gene PAICS expression and evaluate its role in prostate cancer progression. METHODS: Next generation sequencing, qRTPCR and immunoblot analysis revealed an elevated expression of a de novo purine biosynthetic gene, Phosphoribosylaminoimidazole Carboxylase, Phosphoribosylaminoimidazole Succinocarboxamide Synthetase (PAICS) in a progressive manner in prostate cancer. Functional analyses were performed using prostate cancer cell lines- DU145, PC3, LnCaP, and VCaP. The oncogenic properties of PAICS were studied both by transient and stable knockdown strategies, in vivo chicken chorioallantoic membrane (CAM) and murine xenograft models. Effect of BET bromodomain inhibitor JQ1 on the expression level of PAICS was also studied. RESULTS: Molecular staging of prostate cancer is important factor in effective diagnosis, prognosis and therapy. In this study, we identified a de novo purine biosynthetic gene; PAICS is overexpressed in PCa and its expression correlated with disease aggressiveness. Through several in vitro and in vivo functional studies, we show that PAICS is necessary for proliferation and invasion in prostate cancer cells. We identified JQ1, a BET bromodomain inhibitor previously implicated in regulating MYC expression and demonstrated role in prostate cancer, abrogates PAICS expression in several prostate cancer cells. Furthermore, we observe loss of MYC occupancy on PAICS promoter in presence of JQ1. CONCLUSIONS: Here, we report that evaluation of PAICS in prostate cancer progression and its role in prostate cancer cell proliferation and invasion and suggest it as a valid therapeutic target. We suggest JQ1, a BET domain inhibitor, as possible therapeutic option in targeting PAICS in prostate cancer. Prostate 77:10-21, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27550067 TI - Immediate nipple reconstruction with a C-V flap and areolar reconstruction with an autograft of the ipsilateral areola. AB - BACKGROUND: The authors report a new nipple-areolar complex (NAC) reconstruction technique using an autograft of the ipsilateral areola for breast cancer with nipple invasion. METHODS: A total of 43 patients with breast cancer involving nipple invasion underwent oncoplastic surgery with NAC reconstruction. The nipple was reconstructed with a C-V flap, and the areola was autografted onto the new areola bed after the ipsilateral areola was confirmed to be tumour-free. The cosmetic results were self-evaluated by the patients after chemotherapy or radiotherapy according to a 4-point scoring system. RESULTS: Overall satisfaction with the cosmetic result was assessed as follows: excellent (n = 14), good (n = 19), fair (n = 7) or poor (n = 3). Oncological evaluation revealed no cases of local recurrence and five cases of distant metastasis. CONCLUSION: The immediate NAC reconstruction technique involving a C-V flap and autografting of the ipsilateral areola is a feasible method for obtaining realistic areolar reconstruction. PMID- 27550068 TI - Alzheimer's Disease Biomarker Profile in Cerebrospinal Fluid of Individuals with Immune-Mediated Encephalitis. PMID- 27550069 TI - Effect of Contralateral Medial Olivocochlear Feedback on Perceptual Estimates of Cochlear Gain and Compression. AB - The active cochlear mechanism amplifies responses to low-intensity sounds, compresses the range of input sound intensities to a smaller output range, and increases cochlear frequency selectivity. The gain of the active mechanism can be modulated by the medial olivocochlear (MOC) efferent system, creating the possibility of top-down control at the earliest level of auditory processing. In humans, MOC function has mostly been measured by the suppression of otoacoustic emissions (OAEs), typically as a result of MOC activation by a contralateral elicitor sound. The exact relationship between OAE suppression and cochlear gain reduction, however, remains unclear. Here, we measured the effect of a contralateral MOC elicitor on perceptual estimates of cochlear gain and compression, obtained using the established temporal masking curve (TMC) method. The measurements were taken at a signal frequency of 2 kHz and compared with measurements of click-evoked OAE suppression. The elicitor was a broadband noise, set to a sound pressure level of 54 dB to avoid triggering the middle ear muscle reflex. Despite its low level, the elicitor had a significant effect on the TMCs, consistent with a reduction in cochlear gain. The amount of gain reduction was estimated as 4.4 dB on average, corresponding to around 18 % of the without elicitor gain. As a result, the compression exponent increased from 0.18 to 0.27. PMID- 27550070 TI - Rab24 interacts with the Rab7/Rab interacting lysosomal protein complex to regulate endosomal degradation. AB - Endocytosis is a multistep process engaged in extracellular molecules internalization. Several proteins including the Rab GTPases family coordinate the endocytic pathway. The small GTPase Rab7 is present in late endosome (LE) compartments being a marker of endosome maturation. The Rab interacting lysosomal protein (RILP) is a downstream effector of Rab7 that recruits the functional dynein/dynactin motor complex to late compartments. In the present study, we have found Rab24 as a component of the endosome-lysosome degradative pathway. Rab24 is an atypical protein of the Rab GTPase family, which has been attributed a function in vesicle trafficking and autophagosome maturation. Using a model of transiently expressed proteins in K562 cells, we found that Rab24 co-localizes in vesicular structures labeled with Rab7 and LAMP1. Moreover, using a dominant negative mutant of Rab24 or a siRNA-Rab24 we showed that the distribution of Rab7 in vesicles depends on a functional Rab24 to allow DQ-BSA protein degradation. Additionally, by immunoprecipitation and pull down assays, we have demonstrated that Rab24 interacts with Rab7 and RILP. Interestingly, overexpression of the Vps41 subunit from the homotypic fusion and protein-sorting (HOPS) complex hampered the co-localization of Rab24 with RILP or with the lysosomal GTPase Arl8b, suggesting that Vps41 would affect the Rab24/RILP association. In summary, our data strongly support the hypothesis that Rab24 forms a complex with Rab7 and RILP on the membranes of late compartments. Our work provides new insights into the molecular function of Rab24 in the last steps of the endosomal degradative pathway. PMID- 27550071 TI - Influential journals in health research: a bibliometric study. AB - BACKGROUND: There is a wide range of intellectual work written about health research, which has been shaped by the evolution of diseases. This study aims to identify the leading journals over the last 25 years (1990-2014) according to a wide range of bibliometric indicators. METHODS: The study develops a bibliometric overview of all the journals that are currently indexed in Web of Science (WoS) database in any of the four categories connected to health research. The work classifies health research in nine subfields: Public Health, Environmental and Occupational Health, Health Management and Economics, Health Promotion and Health Behavior, Epidemiology, Health Policy and Services, Medicine, Health Informatics, Engineering and Technology, and Primary Care. RESULTS: The results indicate a wide dispersion between categories being the American Journal of Epidemiology, Environmental Health Perspectives, American Journal of Public Health, and Social Science & Medicine, the journals that have received the highest number of citations over the last 25 years. According to other indicators such as the h index and the citations per paper, some other journals such as the Annual Review of Public Health and Medical Care, obtain better results which show the wide diversity and profiles of outlets available in the scientific community. The results are grouped and studied according to the nine subfields in order to identify the leading journals in each specific sub discipline of health. CONCLUSIONS: The work identifies the leading journals in health research through a bibliometric approach. The analysis shows a deep overview of the results of health journals. It is worth noting that many journals have entered the WoS database during the last years, in many cases to fill some specific niche that has emerged in the literature, although the most popular ones have been in the database for a long time. PMID- 27550072 TI - The Role of Preoperative Magnetic Resonance Imaging in the Assessment and Surgical Treatment of Interval and Screen-Detected Breast Cancer in Older Women. AB - We describe the relationship between preoperative magnetic resonance imaging (MRI) and the utilization of additional imaging, biopsy, and primary surgical treatment for subgroups of women with interval versus screen-detected breast cancer. We determined the proportion of women receiving additional breast imaging or biopsy and type of primary surgical treatment, stratified by use of preoperative MRI, separately for both groups. Using Breast Cancer Surveillance Consortium (BCSC) data, we identified a cohort of women age 66 and older with an interval or screen-detected breast cancer diagnosis between 2005 and 2010. Using logistic regression, we explored associations between primary surgical treatment type and preoperative MRI use for interval and screen-detected cancers. There were 204 women with an interval cancer and 1,254 with a screen-detected cancer. The interval cancer group was more likely to receive preoperative MRI (21% versus 13%). In both groups, women receiving MRI were more likely to receive additional imaging and/or biopsy. Receipt of MRI was not associated with increased odds of mastectomy (OR = 0.99, 95% CI: 0.67-1.50), while interval cancer diagnosis was associated with significantly higher odds of mastectomy (OR = 1.64, 95% CI: 1.11 2.42). Older women with interval cancer were more likely than women with a screen detected cancer to have preoperative MRI, however, those with an interval cancer had 64% higher odds of mastectomy regardless of receipt of MRI. Given women with interval cancer are reported to have a worse prognosis, more research is needed to understand effectiveness of imaging modalities and treatment consequences within this group. PMID- 27550073 TI - Genome-wide identification and characterization of long non-coding RNAs in developmental skeletal muscle of fetal goat. AB - BACKGROUND: Long non-coding RNAs (lncRNAs) have been studied extensively over the past few years. Large numbers of lncRNAs have been identified in mouse, rat, and human, and some of them have been shown to play important roles in muscle development and myogenesis. However, there are few reports on the characterization of lncRNAs covering all the development stages of skeletal muscle in livestock. RESULTS: RNA libraries constructed from developing longissimus dorsi muscle of fetal (45, 60, and 105 days of gestation) and postnatal (3 days after birth) goat (Capra hircus) were sequenced. A total of 1,034,049,894 clean reads were generated. Among them, 3981 lncRNA transcripts corresponding to 2739 lncRNA genes were identified, including 3515 intergenic lncRNAs and 466 anti-sense lncRNAs. Notably, in pairwise comparisons between the libraries of skeletal muscle at the different development stages, a total of 577 transcripts were differentially expressed (P < 0.05) which were validated by qPCR using randomly selected six lncRNA genes. The identified goat lncRNAs shared some characteristics, such as fewer exons and shorter length, with the lncRNAs in other mammals. We also found 1153 lncRNAs genes were neighbored 1455 protein coding genes (<10 kb upstream and downstream) and functionally enriched in transcriptional regulation and development-related processes, indicating they may be in cis-regulatory relationships. Additionally, Pearson's correlation coefficients of co-expression levels suggested 1737 lncRNAs and 19,422 mRNAs were possibly in trans-regulatory relationships (r > 0.95 or r < -0.95). These co expressed mRNAs were enriched in development-related biological processes such as muscle system processes, regulation of cell growth, muscle cell development, regulation of transcription, and embryonic morphogenesis. CONCLUSIONS: This study provides a catalog of goat muscle-related lncRNAs, and will contribute to a fuller understanding of the molecular mechanism underpinning muscle development in mammals. PMID- 27550074 TI - Shock Wave-Induced Damage and Poration in Eukaryotic Cell Membranes. AB - Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for a variety of drug delivery applications. However, the mechanisms involved in shock wave-mediated membrane permeabilization are still poorly understood. In this study, the effects on both the permeability and the ultrastructural features of two human cell lineages were investigated after the application of underwater shock waves in vitro. Scanning Electron Microscopy of cells derived from a human embryo kidney (HEK)-293 and Michigan Cancer Foundation (MCF)-7 cells, an immortalized culture derived from human breast adenocarcinoma, showed a small amount of microvilli (as compared to control cells), the presence of hole-like structures, and a decrease in cell size after shock wave exposure. Interestingly, these effects were accompanied by the permeabilization of acid and macromolecular dyes and gene transfection. Trypan blue exclusion assays indicated that cell membranes were porated during shock wave treatment but resealed after a few seconds. Deformations of the cell membrane lasted for at least 5 min, allowing their observation in fixed cells. For each cell line, different shock wave parameters were needed to achieve cell membrane poration. This difference was correlated to successful gene transfection by shock waves. Our results demonstrate, for the first time, that shock waves induce transient micro- and submicrosized deformations at the cell membrane, leading to cell transfection and cell survival. They also indicate that ultrastructural analyses of cell surfaces may constitute a useful way to match the use of shock waves to different cells and settings. PMID- 27550075 TI - Commentary: Rethinking fast and slow based on a critique of reaction-time reverse inference. PMID- 27550076 TI - Gender effect on driving cessation in pre-dementia and dementia phases: results of the 3C population-based study. AB - OBJECTIVES: Aging entails deterioration in sensory, physical, and cognitive functions, raising doubt in the driving capacity of older drivers, especially when the deficits are severe, as in dementia. Many older drivers, especially women, adapt their driving habits in order to compensate for these deficits and eventually stop driving. The present prospective study assessed driving cessation in men and women throughout the dementia process, including a 2-year pre-dementia phase. METHODS: The study was based on a three-city cohort of subjects who were aged 65 years and older in 2000 and followed for more than 10 years. Active dementia detection was conducted at each follow-up. The probability of driving cessation was assessed in men and women during the 2-year pre-dementia phase and until 5 years after diagnosis. RESULTS: In the 2-year pre-dementia phase, both men and women ceased driving earlier than drivers with no central nervous system pathology (p < 0,001), and women ceased driving earlier than men. A total of 45% of men and 74% of women had already ceased driving at dementia diagnosis. In contrast, the probability of cessation within 3 years after diagnosis was similar between men and women. CONCLUSION: The study showed that, in this French urban population, few demented drivers, especially women, were still driving after diagnosis. Those who continued to drive 3 years after the diagnosis all had Alzheimer-type dementia. There is certainly a need for physicians to help these drivers to adapt their driving activity to their deficits and to prepare them to stop driving. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27550077 TI - Integration of diffusion of innovation theory into diabetes care. PMID- 27550083 TI - Orange-red emitting europium doped strontium ortho-silicate phosphor prepared by a solid state reaction method. AB - In the present article we report europium-doped strontium ortho-silicates, namely Sr2 SiO4 :xEu3+ (x = 1.0, 1.5, 2.0, 2.5 or 3.0 mol%) phosphors, prepared by solid state reaction method. The crystal structures of the sintered phosphors were consistent with orthorhombic crystallography with a Pmna space group. The chemical compositions of the sintered phosphors were confirmed by energy dispersive X-ray spectroscopy (EDS). Thermoluminescence (TL) kinetic parameters such as activation energy, order of kinetics and frequency factors were calculated by the peak shape method. Orange-red emission originating from the 5 D0 -7 FJ (J = 0, 1, 2, 3) transitions of Eu3+ ions could clearly be observed after samples were excited at 395 nm. The combination of these emissions constituted orange-red light as indicated on the Commission Internationale de l'Eclairage (CIE) chromaticity diagram. Mechanoluminescence (ML) intensity of the prepared phosphor increased linearly with increasing impact velocity of the moving piston that suggests that these phosphors can also be used as sensors to detect the stress of an object. Thus, the present investigation indicates that the piezo-electricity was responsible for producing ML in the prepared phosphor. PMID- 27550078 TI - In vivo diffusion-tensor MRI of the human heart on a 3 tesla clinical scanner: An optimized second order (M2) motion compensated diffusion-preparation approach. AB - PURPOSE: To optimize a diffusion-prepared balanced steady-state free precession cardiac MRI (CMR) technique to perform diffusion-tensor CMR (DT-CMR) in humans on a 3 Tesla clinical scanner METHODS: A previously developed second order motion compensated (M2) diffusion-preparation scheme was significantly shortened (40%) yielding sufficient signal-to-noise ratio for DT-CMR imaging. In 20 healthy volunteers and 3 heart failure (HF) patients, DT-CMR was performed comparing no motion compensation (M0), first order motion compensation (M1), and the optimized M2. Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and HA transmural slope (HATS) were calculated. Reproducibility and success rate (SR) were investigated. RESULTS: M2-derived left ventricular (LV) MD, FA, and HATS (1.4 +/- 0.2 MUm2 /ms, 0.28 +/- 0.06, -1.0 +/- 0.2 degrees /%trans) were significantly (P < 0.001) less than M1 (1.8 +/- 0.3 MUm2 /ms, 0.46 +/- 0.14, -0.1 +/- 0.3 degrees /%trans) and M0 (4.8 +/- 1.0 MUm2 /ms, 0.70 +/- 0.14, 0.1 +/- 0.3 degrees /%trans) indicating less motion corruption and yielding values more consistent with previous literature. M2-derived DT-CMR parameters had higher reproducible (ICC > 0.85) and SR (82%) than M1 (ICC = 0.20-0.85; SR = 37%) and M0 (ICC = 0.20-0.30; SR = 11%). M2 DT-CMR was able to yield HA maps with smooth transmural transition from endocardium to epicardium. CONCLUSION: The proposed M2 DT-CMR reproducibly yielded bulk motion robust estimations of mean LV MD, FA, HA, and HATS on a 3T clinical scanner. Magn Reson Med 76:1354-1363, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27550085 TI - A lifestyle intervention in primary care prevents deterioration of insulin resistance in patients with impaired glucose tolerance: A randomised controlled trial. AB - AIMS: We hypothesised that the expected increase in insulin resistance over three years' time in individuals with impaired glucose tolerance (IGT) and/or impaired fasting glucose could be attenuated by an intervention with focus on physical activity in ordinary primary care. METHODS: We conducted a randomised controlled trial with 96 participants over three years. Examination of the participants included anthropometric measures, blood pressure, body weight and height, blood samples, an oral glucose tolerance test, and questionnaires about diet and lifestyle. The study subjects were randomised to either an intense intervention with information, group sessions, referral to physical activity and a step counter ( n = 31), a less intense intervention without the group sessions ( n = 35), or care as usual group (CAUG) ( n = 30). Differences between the groups were analysed with general linear models adjusted for age, gender, baseline values and time in the intervention. RESULTS: Individual insulin resistance increased in the CAUG. Due to having a similar effect, we combined the two intervention groups into a combined intervention group (CIG; n = 66) in the analyses. In individuals with IGT, the increase in the homeostatic model assessment-insulin resistance differed significantly between those in the CAUG and the CIG (Delta = 0.8; CI: 0.1-1.6; p = 0.034). Likewise, diastolic blood pressure decreased more in the CIG than in the CAUG (Delta = 5.1; CI: 0.1-10.0; p = 0.047). A total of 17 individuals developed Type 2 diabetes, 23% were in the CIG and 33% in the CAUG; so there was a 32% reduced risk in the intervention group. CONCLUSIONS: A lifestyle intervention focused on physical activity is feasible in ordinary primary care and prevents deterioration in insulin sensitivity in individuals with IGT over a three-year period. PMID- 27550084 TI - Access to timely formal dementia care in Europe: protocol of the Actifcare (ACcess to Timely Formal Care) study. AB - BACKGROUND: Previous findings indicate that people with dementia and their informal carers experience difficulties accessing and using formal care services due to a mismatch between needs and service use. This mismatch causes overall dissatisfaction and is a waste of the scarce financial care resources. This article presents the background and methods of the Actifcare (ACcess to Timely Formal Care) project. This is a European study aiming at best-practice development in finding timely access to formal care for community-dwelling people with dementia and their informal carers. There are five main objectives: 1) Explore predisposing and enabling factors associated with the use of formal care, 2) Explore the association between the use of formal care, needs and quality of life and 3) Compare these across European countries, 4) Understand the costs and consequences of formal care services utilization in people with unmet needs, 5) Determine the major costs and quality of life drivers and their relationship with formal care services across European countries. METHODS: In a longitudinal cohort study conducted in eight European countries approximately 450 people with dementia and informal carers will be assessed three times in 1 year (baseline, 6 and 12 months). In this year we will closely monitor the process of finding access to formal care. Data on service use, quality of life and needs will be collected. DISCUSSION: The results of Actifcare are expected to reveal best practices in organizing formal care. Knowledge about enabling and predisposing factors regarding access to care services, as well as its costs and consequences, can advance the state of the art in health systems research into pathways to dementia care, in order to benefit people with dementia and their informal carers. PMID- 27550086 TI - Multi-spectroscopic and voltammetric evidences for binding, conformational changes of bovine serum albumin with thiamine. AB - The interaction between thiamine hydrochloride (TA) and bovine serum albumin (BSA) was investigated by fluorescence, FTIR, UV-vis spectroscopic and cyclic voltammetric techniques under optimised physiological condition. The fluorescence intensity of BSA is gradually decreased upon addition of TA due to the formation of a BSA-TA complex. The binding parameters were evaluated and their behaviour at different temperatures was analysed. The quenching constants (Ksv) obtained were 2.6 * 104, 2.2 * 104 and 2.0 * 104 L mol-1 at 288, 298 and 308 K, respectively. The binding mechanism was static-type quenching. The values of DeltaH degrees and DeltaS degrees were found to be 26.87 kJ mol-1 and 21.3 J K-1 mol-1, and indicated that electrostatic interaction was the principal intermolecular force. The changes in the secondary structure of BSA upon interaction with TA were confirmed by synchronous and 3-D spectral results. Site probe studies reveal that TA is located in site I of BSA. The effects of some common metal ions on binding of BSA-TA complex were also investigated. PMID- 27550087 TI - Multitask learning improves prediction of cancer drug sensitivity. AB - Precision oncology seeks to predict the best therapeutic option for individual patients based on the molecular characteristics of their tumors. To assess the preclinical feasibility of drug sensitivity prediction, several studies have measured drug responses for cytotoxic and targeted therapies across large collections of genomically and transcriptomically characterized cancer cell lines and trained predictive models using standard methods like elastic net regression. Here we use existing drug response data sets to demonstrate that multitask learning across drugs strongly improves the accuracy and interpretability of drug prediction models. Our method uses trace norm regularization with a highly efficient ADMM (alternating direction method of multipliers) optimization algorithm that readily scales to large data sets. We anticipate that our approach will enhance efforts to exploit growing drug response compendia in order to advance personalized therapy. PMID- 27550088 TI - Obtaining More Accurate Signals: Spatiotemporal Imaging of Cancer Sites Enabled by a Photoactivatable Aptamer-Based Strategy. AB - Early cancer diagnosis is of great significance to relative cancer prevention and clinical therapy, and it is crucial to efficiently recognize cancerous tumor sites at the molecular level. Herein, we proposed a versatile and efficient strategy based on aptamer recognition and photoactivation imaging for cancer diagnosis. This is the first time that a visible light-controlled photoactivatable aptamer-based platform has been applied for cancer diagnosis. The photoactivatable aptamer-based strategy can accurately detect nucleolin overexpressed tumor cells and can be used for highly selective cancer cell screening and tissue imaging. This strategy is available for both formalin-fixed paraffin-embedded tissue specimens and frozen sections. Moreover, the photoactivation techniques showed great progress in more accurate and persistent imaging to the use of traditional fluorophores. Significantly, the application of this strategy can produce the same accurate results in tissue specimen analysis as with classical hematoxylin-eosin staining and immunohistochemical technology. PMID- 27550089 TI - Sphenofrontal distance in euploid and aneuploid fetuses. AB - OBJECTIVE: To examine the sphenofrontal distance (SFD) in a large series of aneuploid fetuses in the second and third trimesters and compare findings with those of a euploid population. METHODS: The database at our unit was searched to identify pregnancies with a diagnosis of trisomy 21, 18 or 13, triploidy or Turner syndrome after 15 weeks' gestation. Stored ultrasound images obtained between 19 and 22 weeks were reviewed. For the normal population, two euploid fetuses matched for gestational age were selected randomly for each aneuploid case. The SFD was measured from the anterior edge of the sphenoid bone to the lowest posterior edge of the frontal bone using on-screen calipers. The SFD measurement was parallel to the long axis of the maxilla. If the sphenoid bone did not extend superiorly enough for direct measurement of the SFD, a tangential line was drawn at the anterior wall of the sphenoid bone and extended cranially. In these cases, the distance between the extended line and the frontal bone was measured. One operator measured the SFD twice and was blinded to the results and karyotype. RESULTS: The study population consisted of 591 pregnancies: 394 euploid fetuses, 122 fetuses with trisomy 21, 45 with trisomy 18, 16 with trisomy 13, eight with Turner syndrome and six with triploidy. For both euploid and aneuploid groups, mean gestational age at examination was 22.8 (range: euploid, 15.0-40.7; aneuploid, 15.0-40.3) weeks. For euploid fetuses, mean SFD was 1.27 cm and measurements ranged from 0.53 cm to 2.56 cm. SFD was significantly dependent on gestational age (SFD = 0.138 + 0.005 * gestational age, P < 0.001, r = 0.802). Mean SFD was significantly smaller in each aneuploid group compared with the euploid population (trisomies 21, 18 and 13: all P < 0.001; triploidy: P = 0.026; Turner syndrome: P = 0.047). For 32 (26.2%), nine (20.0%) and six (37.5%) fetuses with trisomy 21, 18 and 13, respectively, SFD was < 5th percentile. Only one (12.5%) fetus with Turner syndrome and none with triploidy had SFD < 5th percentile. CONCLUSION: In aneuploid fetuses, the SFD is smaller than in their euploid counterparts. However, for a false-positive rate of 5%, the detection rate of trisomy 21 is only 26%. Therefore, using the method we have proposed, it is unlikely that this marker will play a major role in second- and third trimester screening for aneuploidy. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27550091 TI - Hybrid bio-photo-electro-chemical cells for solar water splitting. AB - Photoelectrochemical water splitting uses solar power to decompose water to hydrogen and oxygen. Here we show how the photocatalytic activity of thylakoid membranes leads to overall water splitting in a bio-photo-electro-chemical (BPEC) cell via a simple process. Thylakoids extracted from spinach are introduced into a BPEC cell containing buffer solution with ferricyanide. Upon solar-simulated illumination, water oxidation takes place and electrons are shuttled by the ferri/ferrocyanide redox couple from the thylakoids to a transparent electrode serving as the anode, yielding a photocurrent density of 0.5 mA cm(-2). Hydrogen evolution occurs at the cathode at a bias as low as 0.8 V. A tandem cell comprising the BPEC cell and a Si photovoltaic module achieves overall water splitting with solar to hydrogen efficiency of 0.3%. These results demonstrate the promise of combining natural photosynthetic membranes and man-made photovoltaic cells in order to convert solar power into hydrogen fuel. PMID- 27550090 TI - Functions of interleukin-34 and its emerging association with rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic, synovial inflammation affecting multiple joints, finally leading to extra-articular lesions for which limited effective treatment options are currently available. Interleukin-34 (IL-34), recently discovered as the second colony-stimulating factor-1 receptor (CSF-1R) ligand, is a newly discovered cytokine. Accumulating evidence has disclosed crucial roles of IL-34 in the proliferation and differentiation of mononuclear phagocyte lineage cells, osteoclastogenesis and inflammation. Recently, IL-34 was detected at high levels in patients with active RA and in experimental models of inflammatory arthritis. Blockade of functional IL-34 with a specific monoclonal antibody can reduce the severity of inflammatory arthritis, suggesting that targeting IL-34 or its receptors may constitute a novel therapeutic strategy for autoimmune diseases such as RA. Here, we have comprehensively discussed the structure and biological functions of IL-34, and reviewed recent advances in our understanding of the emerging role of IL-34 in the development of RA as well as its potential utility as a therapeutic target. PMID- 27550092 TI - Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage. AB - Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients. PMID- 27550093 TI - Staircase Quantum Dots Configuration in Nanowires for Optimized Thermoelectric Power. AB - The performance of thermoelectric energy harvesters can be improved by nanostructures that exploit inelastic transport processes. One prototype is the three-terminal hopping thermoelectric device where electron hopping between quantum-dots are driven by hot phonons. Such three-terminal hopping thermoelectric devices have potential in achieving high efficiency or power via inelastic transport and without relying on heavy-elements or toxic compounds. We show in this work how output power of the device can be optimized via tuning the number and energy configuration of the quantum-dots embedded in parallel nanowires. We find that the staircase energy configuration with constant energy step can improve the power factor over a serial connection of a single pair of quantum-dots. Moreover, for a fixed energy-step, there is an optimal length for the nanowire. Similarly for a fixed number of quantum-dots there is an optimal energy-step for the output power. Our results are important for future developments of high-performance nanostructured thermoelectric devices. PMID- 27550094 TI - Evaluating Exercise Prescription and Instructional Methods Used in Tai Chi Studies Aimed at Improving Balance in Older Adults: A Systematic Review. AB - OBJECTIVES: To develop an evaluation instrument to determine to what extent Tai Chi interventions aimed at improving the balance of older adults disclosed their exercise prescription (Ex Rx ) and instructional methods and met best-practice exercise recommendations for balance improvement. DESIGN: Review. SETTING: PubMed, Scopus, and CINAHL databases were searched from their inception until August 22, 2014. PARTICIPANTS: Adults aged 60 and older without debilitating disease. MEASUREMENTS: Three electronic databases were searched to identify randomized controlled trials (RCTs) of Tai Chi interventions aimed at improving balance in older adults without severe debilitating diseases. Three Ex Rx (frequency, time, intervention length) and 10 instructional (e.g., style, number of forms) methods of the included RCTs were evaluated. RESULTS: Twenty-seven interventions were identified from 26 RCTs. On average, Tai Chi was performed for a mean 56.5 +/- 14.4 minutes per session for 2.8 +/- 1.4 sessions per week for 19.7 +/- 12.7 weeks. Most interventions reported all three Ex Rx methods items, with a mean reporting rate of 92.6 +/- 19.2%. For the 10 instructional methods items, the mean reporting rate was 41.1 +/- 18.0%, significantly lower than for the Ex Rx methods items (P < .001). Fewer than half of the interventions reported unsupervised practice (15%), progression (22%), or the use of breathing (30%) and relaxation (15%) techniques. The instructional methods items most important for targeting Tai Chi practice to improve balance were not routinely disclosed, with only 15% reporting names of forms and 52% reporting movement principles. CONCLUSION: Most Tai Chi interventions disclosed their Ex Rx methods yet routinely failed to report instructional methods. To increase the effectiveness of Tai Chi to improve balance in older adults, future RCTs should disclose their Ex Rx and instructional methods, especially methods that target balance. PMID- 27550143 TI - Re-purposing anticoagulation clinics: expanding access to opioid agonist therapy in primary care settings. PMID- 27550144 TI - ADP-ribosylation Factor-related Protein 1 Interacts with NS5A and Regulates Hepatitis C Virus Propagation. AB - The life cycle of hepatitis C virus (HCV) is tightly coupled to the lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have previously screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet (LD) formation using cell culture-grown HCV (HCVcc)-infected cells. In this study, we selected and characterized the gene encoding ADP-ribosylation factor-related protein 1 (ARFRP1). ARFRP1 is essential for LD growth and is involved in the regulation of lipolysis. siRNA-mediated knockdown of ARFRP1 significantly inhibited HCV replication in both subgenomic replicon cells and HCVcc-infected cells. ARFRP1 interacted with NS5A and NS5A partially colocalized with LD. Silencing of ARFRP1 abrogated HCV-induced LD growth and viral protein expressions. Moreover, ARFRP1 recruited synaptosomal-associated protein 23 (SNAP23) to sites in close proximity to LDs in HCV-infected cells. Silencing of ARFRP1 ablated relocalization of SNAP23 to LD. These data indicate that HCV regulates ARFRP1 for LD growth to facilitate viral propagation and thus ARFRP1 may be a potential target for antiviral therapy. PMID- 27550146 TI - Kidney Donor Profile Index: Can it be extrapolated to our enviroment? PMID- 27550145 TI - High-Density Recombinant Adeno-Associated Viral Particles are Competent Vectors for In Vivo Transduction. AB - Recombinant adeno-associated viral (rAAV) vectors have recently achieved clinical successes in human gene therapy. However, the commonly observed, heavier particles found in rAAV preparations have traditionally been ignored due to their reported low in vitro transduction efficiency. In this study, the biological properties of regular and high-density rAAV serotype 8 vectors, rAAVRD and rAAVHD, were systemically compared. Results demonstrated that both rAAVRD and rAAVHD exhibited similar DNA packaging profiles, while rAAVHD capsids contained fewer VP1 and VP2 proteins, indicating that the rAAVHD particles contained a higher DNA/protein ratio than that of rAAVRD particles. Dynamic light scattering and transmission electron microscopy data revealed that the diameter of rAAVHD was smaller than that of rAAVRD. In vitro, rAAVHD was two- to fourfold less efficient in transduction compared with rAAVRD. However, the transduction performance of rAAVHD and rAAVRD was similar in vivo. No significant difference in neutralizing antibody formation against rAAVRD and rAAVHD was observed, suggesting that the surface epitopes of rAAVRD and rAAVHD are congruent. In summary, the results of this study demonstrate that rAAVRD and rAAVHD are equally competent for in vivo transduction, despite their difference in vitro. Therefore, the use of rAAVHD vectors in human gene therapy should be further evaluated. PMID- 27550148 TI - Guideline choice for CTG analysis influences first caesarean decision. AB - OBJECTIVE: To compare intrapartum cardiotocography (CTG) analysis in case of first caesarean section (CS) for non-reassuring CTG according to international guidelines. METHODS: Four ObGyns retrospectively analysed first CS for non reassuring CTG during labour blind to neonatal outcome. CTG were analysed according to French National College of Obstetricians and Gynaecologists (CNGOF) and to the FIGO guidelines. First, CTG analysis was done without obstetrical context, then secondly, it was given. ObGyns stated if CS was justified or not. Inter-operator ObGyn agreement was analysed. RESULTS: Among 587 CS, 100 women met the inclusion criteria with a first CS for non-reassuring CTG. The overall inter observer agreement was low but fair. ObGyns were significantly more concordant using the FIGO than the CNGOF guidelines (kappa coefficient = 0.331 [0.27-0.39] versus 0.209 [0.16-0.26] p < 0.001). Without obstetrical context 70% of CS were considered as unjustified. This rate decreased to 16% with the knowledge of the obstetrical context and the use of a classification (p < 0.001). Two-third of the unjustified CS were carried out during night hours (p = 0.026). CONCLUSION: The FIGO guidelines are more reproducible than CNGOF guidelines. The overall inter observer agreement was low but fair. The guideline choice could have an impact on first CS decision. PMID- 27550147 TI - Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth. AB - Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID- 27550149 TI - Copper(i)-catalyzed radical decarboxylative imidation of carboxylic acids with N fluoroarylsulfonimides. AB - An efficient copper-catalyzed radical decarboxylative imidation reaction is presented. This strategy is carried out through the copper(i)-catalyzed decarboxylative C(sp(3))-N and C(sp(2))-N coupling of carboxylic acids with N fluoroarylsulfonimides. The reaction shows good functional group tolerance and it provides a new approach for decarboxylative imidation. Preliminary mechanistic studies of this transformation suggest an involvement of N-centered radical species. PMID- 27550151 TI - Short Synthesis of Sulfur Analogues of Polyaromatic Hydrocarbons through Three Palladium-Catalyzed C-H Bond Arylations. AB - An expeditious synthesis of a wide range of phenanthro[9,10-b]thiophene derivatives, which are a class of polyaromatic hydrocarbon (PAH) containing a sulfur atom, is reported. The synthetic scheme involves only two operations from commercially available thiophenes, 2-bromobenzenesulfonyl chlorides and aryl bromides. In the first step, palladium-catalyzed desulfitative arylation using 2 bromobenzenesulfonyl chlorides allows the synthesis of thiophene derivatives, which are substituted at the C4 position by an aryl group containing an ortho bromo substituent. Then, a palladium-catalyzed one-pot cascade intermolecular C5 arylation of thiophene using aryl bromides followed by intramolecular arylation led to the corresponding phenanthro[9,10-b]thiophenes in a single operation. In addition, PAHs containing two or three sulfur atoms, as well as both sulfur and nitrogen atoms, were also designed by this strategy. PMID- 27550150 TI - Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma. AB - Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients. PMID- 27550152 TI - The Pharmacology and Toxicology of the 'Holy Trinity'. AB - Combining opioids with benzodiazepines and skeletal muscle relaxants ('The Holy Trinity') has been reported to potentiate the 'high'. Through unique interactions with colocalized MU-opioid and GABAA receptors, the combined use of these agents induces a synergistic increase in dopamine in the nucleus accumbens (NAc) and depression of respiration. The inhibition of GABA release mediated by MU1 -opioid receptor activation results in a subsequent increase in dopamine in the NAc. Benzodiazepines activate the GABAA R to suppress respiration in the medullary respiratory centres. The skeletal muscle relaxant, carisoprodol, appears to bind to a unique binding domain within the GABAA R to further enhance the respiratory depressant effects of the benzodiazepines. Therefore, the opioids, the benzodiazepines and carisoprodol alone or in combination are capable of inducing respiratory depression. Current guidelines for opioid prescribing recommend against the concomitant use of benzodiazepines but do not recognize the potential risk associated with the addition of skeletal muscle relaxants. PMID- 27550153 TI - Young people who are being bullied - do they want general practice support? AB - BACKGROUND: Childhood bullying is a major risk factor for health, education and social relationships, with effects persisting into adulthood. It affects half of all children at some point, with 10-14 % experiencing bullying that lasts for years. With the advent of cyberbullying, it can happen at all times and places. There have been calls for GPs to take a more active role in identifying and supporting young people who are being bullied. This paper explores young people's and parents' opinions about whether general practice should be involved in identifying and supporting young people who are being bullied. METHODS: Two hundred six young people (85.9 % female, mean +/- sd age 16.2 +/- 3.2 years) and 44 parents were recruited through established bullying charity websites and their social media channels to complete an online questionnaire comprising multiple choice questions and unlimited narrative responses. Questionnaire responses were analysed by age and gender using descriptive statistics. A descriptive analysis of the narrative responses was undertaken and key themes identified. RESULTS: Young people (90.8 %) and parents (88.7 %) thought it was important for GPs to be better able to recognise and help young people who are being bullied. Most recognised the link between bullying and health. The doctor's independence was seen as advantageous. Young people preferred completing a screening questionnaire to disclose experience of being bullied than being asked directly. They expressed concerns about how questions would be asked and whether information would be shared with parents/guardians. Parents were supportive of the use of a screening questionnaire, and most expected their child's disclosure to be shared with them. CONCLUSION: Young people and parents recruited through anti-bullying websites and social media would welcome greater GP involvement in identifying and supporting young people who are being bullied and their families, provided it is offered in a caring, compassionate and confidential manner. PMID- 27550154 TI - Analysis of 22 Elements in Milk, Feed, and Water of Dairy Cow, Goat, and Buffalo from Different Regions of China. AB - The objectives of this study were to measure the concentrations of elements in raw milk by inductively coupled plasma-mass spectrometry (ICP-MS) and evaluate differences in element concentrations among animal species and regions of China. Furthermore, drinking water and feed samples were analyzed to investigate whether the element concentrations in raw milk are correlated with those in water and feed. All samples were analyzed by ICP-MS following microwave-assisted acid digestion. The mean recovery of the elements was 98.7 % from milk, 103.7 % from water, and 93.3 % from a certified reference material (cabbage). Principal component analysis results revealed that element concentrations differed among animal species and regions. Correlation analysis showed that trace elements Mn, Fe, Ni, Ga, Se, Sr, Cs, U in water and Co, Ni, Cu, Se, U in feed were significantly correlated with those in milk (p < 0.05). Toxic and potential toxic elements Cr, As, Cd, Tl, Pb in water and Al, Cr, As, Hg, Tl in feed were significantly correlated with those in milk (p < 0.05). Results of correlation analysis revealed that elements in water and feed might contribute to the elements in milk. PMID- 27550155 TI - Clinical and Pathologic Features of a Suspected Selenium Deficiency in Captive Plains Zebras. AB - Previous studies have shown that selenium (Se) deficiency is associated with nutritional myopathy, known as white muscle disease (WMD), in horses. However, correlations between Se deficiency and clinical findings, such as hematologic biochemical values and pathological features, have not been evaluated in captive plains zebras. The purpose of the present study was to investigate the clinical and pathologic features that may be caused by a Se deficiency in the captive plains zebra. Clinical findings, feed analyses, hematologic biochemical analyses, response to treatment, and pathologic examination were assessed in six affected plains zebras. The dietary concentration of Se in feed was also tested. Sudden death occurred in two cases during the first day of the onset of symptoms. Two zebras died at 4 days and two zebras survived after treatment. The clinical signs in affected animals were characterized by general weakness, astasia, and abnormal postural positions. The Se concentration in hay from the breeding stable was low, based on the reference value. Glutathione peroxidase (GSH-Px) activity was lower compared with the equine reference value. Multiple areas of subcutaneous steatitis and pale skeletal muscle and myocardium were revealed at gross necropsy. Degeneration and necrosis of myocardial and skeletal muscles, as well as congestion of the liver, lung, and kidney were found via histopathological examination. No suspected bacterial infections were found. Feed analyses, response to treatment, serum GSH-Px activity, and pathological features suggest that Se deficiency may have caused the disease in the six affected captive plains zebra. PMID- 27550158 TI - Fighting cytomegalovirus-caused diseases: the immunologic approach. PMID- 27550156 TI - Selenium Alleviates Oxidative Stress and Lung Damage Induced by Aluminum Chloride in Adult Rats: Biochemical and Histological Approach. AB - Our study pertains to the potential ability of selenium, used as a nutritional supplement, to alleviate oxidative stress induced by aluminum chloride in the lung tissue. Rats have received during 21 days either aluminum chloride (AlCl3) (400 ppm) via drinking water, AlCl3 associated with Na2SeO3 (0.5 mg/kg of diet), or only Na2SeO3. Exposure of rats to AlCl3 induced lung oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. An alteration of lactate dehydrogenase activities and antioxidant redox status, enzymatic (catalase, superoxide dismutase, and glutathione peroxidase), and non enzymatic (non-protein thiols, glutathione, metallothionein, and vitamin C) was also observed. These biochemical modifications were substantiated by histopathological data showing alveolar edema, a large number of hemosiderin laden macrophages, and emphysema. Se supplementation attenuated the levels of oxidative stress by restoring antioxidant state and improved lung histological damage. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing lung damage. PMID- 27550159 TI - Parental hopes, interventions, and survival of neonates with trisomy 13 and trisomy 18. AB - Trisomy 13 and 18 are life-limiting conditions for which a palliative approach is frequently recommended. The objective of this study was to examine parental goals/decisions, the length of life of their child and factors associated with survival. Parents of children who lived with trisomy 13 or 18 that were part of English-speaking social networks were invited to participate in a questionnaire study. Participants answered questions about their hopes/goals, decisions regarding neonatal interventions, and the duration of their children's lives. The participants were 332 parents who answered questions about their 272 children (87% response rate based on site visits; 67% on invitations sent). When parents were asked about their hope after the diagnosis, the main themes invoked by parents were the following: meet their child alive (80% of parents with a prenatal diagnosis), spend some time as a family (72%), bring their child home (52%), and give their child a good life (66%). Parents wanted to give them a chance, but also reported their fears were medical complexity, pain and/or life in the hospital (61%). Healthcare providers recommended comfort care at birth to all parents. Life-sustaining interventions "as for any other child" was chosen as a plan of care by 25% of parents. Of the 216 children with full trisomy, 69% were discharged home after birth and 40% lived >1 y. The presence of a prenatal diagnosis was the strongest independent factor negatively associated with longevity: 36% of children with a prenatal diagnosis lived <24 hr and 47% were discharged home compared to 1% and 87%, respectively for children with a postnatal diagnosis (P < 0.01). Male gender, low-birth weight, and cardiac and/or cerebral anomaly were also associated with decreased survival (P < 0.05). After a prenatal diagnosis, palliative care at birth consisted of limited interventions, whereas after a postnatal diagnosis (median age of 6 days) it consisted of various interventions, including oxygen, ventilation, tube feeding and intravenous fluids, complicating the analysis. In conclusion, the goals of parents of children with trisomy 13 or 18 were to meet their child, be discharged home and be a family. Having a postnatal diagnosis was the independent factor most associated with these goals. Children with a postnatal diagnosis were treated "as any other children" until the diagnosis, which may give them a survival advantage, independent of palliative care. Rigorous transparency regarding specific interventions and outcomes may help personalize care for these children. (c) 2016 Wiley Periodicals, Inc. PMID- 27550160 TI - Impacts of Rotation Schemes on Ground-Dwelling Beneficial Arthropods. AB - Crop rotation alters agroecosystem diversity temporally, and increasing the number of crops in rotation schemes can increase crop yields and reduce reliance on pesticides. We hypothesized that increasing the number of crops in annual rotation schemes would positively affect ground-dwelling beneficial arthropod communities. During 2012 and 2013, pitfall traps were used to measure activity density and diversity of ground-dwelling communities within three previously established, long-term crop rotation studies located in Wisconsin and Illinois. Rotation schemes sampled included continuous corn, a 2-yr annual rotation of corn and soybean, and a 3-yr annual rotation of corn, soybean, and wheat. Insects captured were identified to family, and non-insect arthropods were identified to class, order, or family, depending upon the taxa. Beneficial arthropods captured included natural enemies, granivores, and detritivores. The beneficial community from continuous corn plots was significantly more diverse compared with the community in the 2-yr rotation, whereas the community in the 3-yr rotation did not differ from either rotation scheme. The activity-density of the total community and any individual taxa did not differ among rotation schemes in either corn or soybean. Crop species within all three rotation schemes were annual crops, and are associated with agricultural practices that make infield habitat subject to anthropogenic disturbances and temporally unstable. Habitat instability and disturbance can limit the effectiveness and retention of beneficial arthropods, including natural enemies, granivores, and detritivores. Increasing non-crop and perennial species within landscapes in conjunction with more diverse rotation schemes may increase the effect of biological control of pests by natural enemies. PMID- 27550161 TI - Transgenic Expression of a Viral Cystatin Gene CpBV-CST1 in Tobacco Confers Insect Resistance. AB - A viral gene, CpBV-CST1, was identified from a polydnavirus Cotesia plutellae bracovirus (CpBV). Its protein product was significantly toxic to lepidopteran insects. This study generated a transgenic tobacco plant expressing CpBV-CST1 Expression of transgene CpBV-CST1 was confirmed in T1 generation (second generation after transgenesis) in both mRNA and protein levels. Young larvae of Spodoptera exigua (Hubner) suffered high mortalities after feeding on transgenic tobacco. All 10 T1 transgenic tobacco plants had no significant variation in speed-to-kill. In order to further explore insect resistance of these transgenic tobaccos, bioassays were performed by assessing antixenosis and antibiosis. S. exigua larvae significantly avoided T1 plants in a choice test. Larvae fed with T1 plant exhibited significant decrease in protease activity in the midgut due to consuming CpBV-CST1 protein produced by the transgenic plant. Furthermore, the transgenic tobacco exhibited similar insect resistance to other tobacco-infesting insects, including a leaf-feeding insect, Helicoverpa assulta, and a sap-feeding insect, Myzus persicae These results demonstrate that a viral cystatin gene can be used to develop insect-resistant transgenic plant, suggesting a prospective possibility of expanding the current transgenic approach to high-valued crops. PMID- 27550162 TI - The Impact of Tropical Peat Fire on Termite Assemblage in Sumatra, Indonesia: Reduced Complexity of Community Structure and Survival Strategies. AB - Tropical peat swamp forests in Southeast Asia account for approximately 72% of global peatland. However, extensive forest exploitation following peat drainage for agricultural expansion has been leading to catastrophic peat fires. In this study, we compared the termite assemblage in burnt and unburnt peats in Sumatra, Indonesia. We also identified which taxonomic group is particularly resistant to fire disturbance and the traits that correlate with its persistence in fire impacted peatlands. Overall, the termite species richness in fire-impacted peats was up to 40% lower than that of the total species found in peat swamp forests. Although the estimated species richness values in fire-impacted peats and peat swamp forests were not significantly different, fire changed termite community structure significantly. Only termites of the family Rhinotermitidae survived in the fire event, whereas members of the Termitidae that were reportedly resilient to fire and open habitats elsewhere disappeared during the fire events. The rhinotermitids found in the burnt sites were exclusively wood nesters. This suggests that the desiccation tolerance of termites in open habitat is not the simple underlying survival strategy, but tree branches and barks might have provided a refuge from heat during fire. The result also suggests that the high similarity in species composition in recently burnt peats and long burnt peats implies low species turnover. Thus, regardless of how much time had passed since the fire-impacted peats were abandoned or cultivated, the increase in habitat complexity did not favor colonization by the forest-dependent group. PMID- 27550163 TI - Shifts in Plant Assemblages Reduce the Richness of Galling Insects Across Edge Affected Habitats in the Atlantic Forest. AB - Impacts of habitat loss and fragmentation on specialist herbivores have been rarely addressed. Here we examine the structure of plant and galling insect assemblages in a fragmented landscape of the Atlantic forest to verify a potential impoverishment of these assemblages mediated by edge effects. Saplings and galling insects were recorded once within a 0.1-ha area at habitat level, covering forest interior stands, forest edges, and small fragments. A total of 1,769 saplings from 219 tree species were recorded across all three habitats, with differences in terms of sapling abundance and species richness. Additionally, edge-affected habitats exhibited reduced richness of both host plant and galling insects at plot and habitat spatial scale. Attack levels also differed among forest types at habitat spatial scale (21.1% of attacked stems in forest interior, 12.4% in small fragments but only 8.5% in forest edges). Plot ordination resulted in three clearly segregated clusters: one formed by forest interior, one by small fragments, and another formed by edge plots. Finally, the indicator species analysis identified seven and one indicator plant species in forest interior and edge-affected habitats, respectively. Consequently, edge effects lead to formation of distinct taxonomic groups and also an impoverished assemblage of plants and galling insects at multiple spatial scales. The results of the present study indicate that fragmentation-related changes in plant assemblages can have a cascade effects on specialist herbivores. Accordingly, hyperfragmented landscapes may not be able to retain an expressive portion of tropical biodiversity. PMID- 27550165 TI - Carcass Age and Reproductive Costs for Nicrophorus orbicollis (Coleoptera: Silphidae). AB - The life history costs of living in microbially dense environments can be high. To assess the importance of these costs for natural selection, it is necessary to know how costs vary with environmental conditions. Adult burying beetles prepare vertebrate carcasses of varying age and states of deterioration as a resource for their young. In the present study, Nicrophorus orbicollis Say females were presented with either fresh or aged (80 h) large carcasses (30-39 g) to examine effects on their lifetime reproductive success (four reproductive attempts) and survival. Reproductive success and survival were also measured for female offspring that developed on fresh and aged carcasses. Carcass age had no measurable effect on lifetime reproductive output or life span of either parents or their adult offspring. In a separate experiment using medium-sized carcasses (22-24 g), the reproductive performance of females in a single reproductive attempt was negatively affected by carcass age (13.9% less brood mass). The results suggest that the costs of using a single older carcass are relatively minor when measured over a lifetime. Alternative costs of using older carcasses and explanations for the complex antimicrobial traits of burying beetles are discussed. PMID- 27550164 TI - Frugivory by Brown Marmorated Stink Bug (Hemiptera: Pentatomidae) Alters Blueberry Fruit Chemistry and Preference by Conspecifics. AB - The brown marmorated stink bug, Halyomorpha halys (Stal), is an invasive pest from Asia that feeds on many agricultural crops in the United States, including blueberries. Yet, the effects of H. halys feeding on fruit chemistry and induced resistance to insects remain unknown. Here we hypothesized that frugivory by H. halys changes fruit chemical composition, which in turn affects insect feeding behavior. In field experiments, blueberry fruit was either mechanically injured or injured by 0 (control), 2, 5, or 10 H. halys Total soluble solids ( degrees Brix) and anthocyanin and phenolic content in injured and uninjured fruits, as well as their effects on feeding behavior by conspecifics, were measured subsequently in the laboratory. Results showed lower degrees Brix values in injured fruit as compared with uninjured fruit. Fruit injured by 2 and 5 H. halys also had 32 and 20% higher total phenolics, respectively, than the uninjured controls. The proportions of the anthocyanins derived from delphinidin, cyanidin, and petunidin increased, whereas those from malvidin decreased, in fruit after mechanical wounding and frugivory by H. halys In dual-choice tests, H. halys fed more often on uninjured fruit than those previously injured by conspecifics. These results show that frugivory by H. halys reduces the amounts of soluble solids, alters anthocyanin ratios, and increases levels of phenolics, and, as a result, injured fruits were a less preferred food source for conspecifics. To our knowledge, this is the first study to investigate the effects of frugivory on fruit chemistry and induced fruit resistance against a fruit-eating herbivore. PMID- 27550166 TI - Assessment of a Cross-Vane Trap as a Tool for Sampling the Invasive Megacopta cribraria (Hemiptera: Plataspidae) in Soybean with Associated Evaluations of Female Reproductive Status. AB - Megacopta cribraria (F.) (Hemiptera: Plataspidae) is an established pest of soybean, Glycine max (L.) Merrill, in the southeastern United States. Populations of this pest in soybean are typically estimated using sweep nets, a time consuming procedure. Cross-vane traps may provide an alternative to using sweep nets. The relationship between trap and sweep-net sampling, and the effect of distance from field edges on M. cribraria densities were studied in 2013 and 2014. Adults were detected in the traps up to 3 wk before they were present in the sweep-net samples. Adults and nymphs collected from trap and sweep-net sampling decreased from the field edge toward the field interior. Across all dates and distances, there was a strong positive association between the two sampling methods (r = 0.60), but only 36% of location analyses by week showed significant association. Females collected using both sampling methods were dissected and rated based on egg development. Female populations of all reproductive maturities dispersed into soybean, but proportions varied with sampling method. Results provide a foundation for work into understanding dispersal cues, with implications for management in soybean. Cross-vane traps may serve as an early-season tool to monitor populations, but more studies are needed before robust sampling recommendations can be defined. PMID- 27550167 TI - AthMethPre: a web server for the prediction and query of mRNA m6A sites in Arabidopsis thaliana. AB - N6-Methyladenosine (m6A) is the most prevalent and abundant modification in mRNA that has been linked to many key biological processes. High-throughput experiments have generated m6A-peaks across the transcriptome of A. thaliana, but the specific methylated sites were not assigned, which impedes the understanding of m6A functions in plants. Therefore, computational prediction of mRNA m6A sites becomes emergently important. Here, we present a method to predict the m6A sites for A. thaliana mRNA sequence(s). To predict the m6A sites of an mRNA sequence, we employed the support vector machine to build a classifier using the features of the positional flanking nucleotide sequence and position-independent k-mer nucleotide spectrum. Our method achieved good performance and was applied to a web server to provide service for the prediction of A. thaliana m6A sites. The server also provides a comprehensive database of predicted transcriptome-wide m6A sites and curated m6A-seq peaks from the literature for query and visualization. The AthMethPre web server is the first web server that provides a user-friendly tool for the prediction and query of A. thaliana mRNA m6A sites, which is freely accessible for public use at . PMID- 27550168 TI - Analysing Cytochrome c Aggregation and Fibrillation upon Interaction with Acetonitrile: an in Vitro Study. AB - The propensity of native state to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. Our study was focused at analyzing the aggregation and fibrillation tendency of cytochrome c in presence of an organic solvent i.e. acetonitrile. In vitro analysis revealed that the interaction of cytochrome c with acetonitrile facilitated the oligomerization of cytochrome c via the passage through an intermediate state which was obtained at 20 % v/v concentration of acetonitrile featured by a sharp hike in the ANS fluorescence intensity with a blue shift of 20 nm compared to the native state. Oligomers and fibrils were formed at 40 and 50 % v/v concentration respectively as indicated by a significant hike in the ThT fluorescence intensity, red shift of 55 nm in congo red binding assay and an increase in absorbance at 350 nm. They possess beta sheet structure as evident from appearance of peak at 217 nm. Finally, authenticity of oligomeric and fibrillar species was confirmed by TEM imaging which revealed bead like aggregates and a meshwork of thread like fibrils respectively. It could be suggested that the fibrillation of bovine cytchrome c could serve as a model protein to unravel the general aggregation and fibrillation pattern of heme proteins. Graphical abstract ?. PMID- 27550169 TI - Clinicopathological and molecular study of primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoma. AB - BACKGROUND: Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma (CD4+ PCSM-TCL) is a rare lymphoproliferative disorder with a favorable prognosis. Distinguishing it from other cutaneous lymphomas is often a challenge. METHODS: We retrospectively collected CD4+PCSM-TCL cases from two centers (MD Anderson Cancer Center, USA and University of Milan, Italy) and evaluated their clinicopathological features. Array-comparative genomic hybridization (aCGH) analysis was performed on 11 cases. RESULTS: A total of 62 patients were identified. Single lesions were the most common clinical presentations (79%). Five patients (8%) showed multiple MF-like plaques. All patients' disease had an indolent course. The infiltrate was nodular and diffuse, multinodular or superficial but in all cases, it was characterized by small/medium pleomorphic CD4+/CD279(PD1+) lymphocytes grouped in clusters and 'pseudorosettes' around B cells. aCGH analysis showed no significant genomic abnormalities. Single lesions were mainly treated with surgical excision (91%) and/or radiotherapy (95%) with low rate of relapse (12%). For multiple lesions, topical steroids, nitrogen mustard and phototherapy were mainly used but the rate of relapse was high (69%). CONCLUSIONS: CD4+PCSM-TCL is characterized by heterogeneous clinical presentations. The arrangement of atypical cells in clusters or pseudorosettes is a useful criterion for diagnosis. The absence of significant genomic alterations is in agreement with its indolent behavior. PMID- 27550172 TI - Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant: a case report. AB - BACKGROUND: Ganciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them. CASE PRESENTATION: We treated an extremely premature female infant with postnatal cytomegalovirus infection with intravenous administration of ganciclovir since 49 days of life (postmenstrual age of 31 weeks). After ganciclovir treatment was initiated at a dose of 5 mg/kg every 12 h, cytomegalovirus loads in the peripheral blood were markedly decreased. However, since plasma ganciclovir trough level was too high, the interval was extended to every 24 h. Subsequently, the trough level and the estimated 12-h area under the concentration-time curve (AUC0-12) were decreased from 3.5 mg/L to 0.3 mg/L and 53.9 mg . h/L to 19.2 mg . h/L, respectively, resulting in an exacerbation of viremia and clinical condition. Adjustment of dosing interval from 24 h to 12 h led to a peak level of 4.2 mg/L, trough level of 1.1 mg/L, and AUC0-12 of 31.8 mg . h/L, resulting in a marked suppression of viral load. CONCLUSIONS: Monitoring the therapeutic drug levels and cytomegalovirus loads is useful in obtaining a proper treatment effect and preventing overdosage during ganciclovir therapy in premature infants with postnatal cytomegalovirus infection. PMID- 27550173 TI - Cuprizone demyelination induces a unique inflammatory response in the subventricular zone. AB - BACKGROUND: Cuprizone leads to demyelination of the corpus callosum (CC) and activates progenitor cells in the adjacent subventricular zone (SVZ), a stem cell niche which contributes to remyelination. The healthy SVZ contains semi-activated microglia and constitutively expresses the pro-inflammatory molecule galectin-3 (Gal-3) suggesting the niche uniquely regulates inflammation. METHODS: We studied the inflammatory response to cuprizone in the SVZ and CC in Gal-3 knockout mice using immunohistochemistry and with the in vitro neurosphere assay. RESULTS: Cuprizone caused loss of myelin basic protein (MBP) immunofluorescence in the CC suggesting demyelination. Cuprizone increased the density of CD45+/Iba1+ microglial cells and also increased Gal-3 expression in the CC. Surprisingly, the number of Gal-3+ and CD45+ cells decreased in the SVZ after cuprizone, suggesting inflammation was selectively reduced therein. Inflammation can regulate SVZ proliferation and indeed the number of phosphohistone H3+ (PHi3+) cells decreased in the SVZ but increased in the CC in both genotypes after cuprizone treatment. BrdU+ SVZ cell numbers also decreased in the SVZ after cuprizone, and this effect was significantly greater at 3 weeks in Gal-3 (-/-) mice compared to WT, suggesting Gal-3 normally limits SVZ cell emigration following cuprizone treatment. CONCLUSIONS: This study reveals a uniquely regulated inflammatory response in the SVZ and shows that Gal-3 participates in remyelination in the cuprizone model. This contrasts with more severe models of demyelination which induce SVZ inflammation and suggests the extent of demyelination affects the SVZ neurogenic response. PMID- 27550174 TI - Novel regulations of MEF2-A, MEF2-D, and CACNA1S in the functional incompetence of adipose-derived mesenchymal stem cells by induced indoxyl sulfate in chronic kidney disease. AB - Indoxyl sulfate (IS) is a digestive intermediate product that is a known indicator of chronic kidney disease. Its toxicity has also been suggested to accelerate chronic kidney disease. Recently, mesenchymal stem cells (MSCs) have been confirmed as a potential treatment in kidney regeneration. To determine the universal alteration in gene expression, we combined high-throughput microarray technology and in vitro culture of adipose-derived mesenchymal stem cells at different doses of IS (20, 40, 60 mg/l). We found that indoxyl sulfate has a remarkable interconnection with stem cell and calcium/calmodulin-dependent kinase pathways. In vitro results showed that indoxyl sulfate exerts anti-proliferation and anti-migration effects on ADMSCs. In addition, IS effects lead to increase in apoptotic cells and cells arrested at the G1 phase. Moreover, MEF2-A, MEF2-D and CACNA1S expression significantly decreased after indoxyl sulfate treatment. It can be speculated that following treatment with indoxyl sulfate, the function of ADMSCs is decreased and ADMSCs' ability to support renal tubule regeneration in chronic kidney disease patients may be lower. PMID- 27550176 TI - Practice-Based Research Networks: Integrating Clinical Data for Improved Pharmacoepidemiology. AB - Pharmacovigilance is concerned with the detection, assessment, understanding, and prevention of adverse reactions to medicines. It is helpful to prevent undesired harm sustained by the patient due to inappropriate or unsafe use of medicinal agents. As the use of drugs and polypharmacy increase in prevalence, pharmacovigilance gains relevance and momentum. Practice-based research networks have the potential to enhance health research by promoting earlier detection of adverse events at a decreased level of cost. This article explores the recent evidence of an improved benefit of administering non-steroidal antiinflammatory drugs (NSAIDs) in the fasting state, and authors propose that an improved pharmacovigilance system is both needed and feasible provided records are adapted to a nationwide integration of pharmacoepidemiology data. PMID- 27550175 TI - Validity of data collected in BIOREG, the Austrian register for biological treatment in rheumatology: current practice of bDMARD therapy in rheumatoid arthritis in Austria. AB - BACKGROUND: The purpose of the present study was to check the validity of data collected in BIOREG, the Austrian register for biological treatment in rheumatology, and to elucidate eventual differences with respect to disease activity (DA) in patients with rheumatoid arthritis (RA) on established biological DMARDs (bDMARDs) before inclusion into the register (EST) and beginners at the time point of inclusion (NEW) after 1 year of treatment. METHODS: RA patients with a complete follow-up of 1 year in BIOREG were divided into EST and NEW and compared with respect to DA, remission rates, concomitant synthetic DMARDs (csDMARDs) and glucocorticoid therapy (GC) at baseline and after 1-year follow-up. Safety concerns are listed. Descriptive statistics are applied. RESULTS: For 346 RA patients (284 EST, 62 NEW) out of 970 RA patients included into BIOREG, a full data set for a 1-year follow-up was available. No differences in DA were observed after 1 year as expressed by DAS28 or RADAI-5, and small differences as expressed by remission rates according to DAS28, RADAI-5 or Boolean criteria (namely approximately 1/2, 1/3 to 1/4 and 1/4 to 1/5 of the patients respectively). Sixty-four adverse events (AEs) were noted in 56 (20 %) of EST and 20 in 19 (31 %) of NEW patients. Malignancy occurred in four patients. After 1 year, 48 % of EST patients but only 16 % of NEW patients were on bDMARD monotherapy. CONCLUSION: Regarding DA, the date collected in BIOREG appeared to be valid. After 1 year of bDMARD therapy, all patients, whether EST or NEW, achieved a similar level of DA. AEs occurred more frequently during the early phase of bDMARD treatment. Austrian rheumatologists initiate bDMARD therapy in patients with lower disease levels than in other European countries, leading to high remission rates. PMID- 27550177 TI - Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a "real-world" observational study in the United States. AB - BACKGROUND: Limited data are available about the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVES: To compare the major bleeding risk among newly anticoagulated non-valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States. METHODS AND RESULTS: A retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan((r)) Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12-3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26-3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94-3.10, P=.079) had a non-significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30-0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91-1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64-1.21, P=.446) had a non-significant major bleeding risk vs warfarin. CONCLUSION: Among newly anticoagulated NVAF patients in the real-world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings. PMID- 27550178 TI - PAtCh-Cap: input strategy for improving analysis of ChIP-exo data sets and beyond. AB - Recently, a number of advances have been implemented into the core ChIP-seq (chromatin immunoprecipitation coupled with next-generation sequencing) methodology to streamline the process, reduce costs or improve data resolution. Several of these emerging ChIP-based methods perform additional chemical steps on bead-bound immunoprecipitated chromatin, posing a challenge for generating similarly treated input controls required for artifact removal during bioinformatics analyses. Here we present a versatile method for producing technique-specific input controls for ChIP-based methods that utilize additional bead-bound processing steps. This reported method, termed protein attached chromatin capture (PAtCh-Cap), relies on the non-specific capture of chromatin bound proteins via their carboxylate groups, leaving the DNA accessible for subsequent chemical treatments in parallel with chromatin separately immunoprecipitated for the target protein. Application of this input strategy not only significantly enhanced artifact removal from ChIP-exo data, increasing confidence in peak identification and allowing for de novo motif searching, but also afforded discovery of a novel CTCF binding motif. PMID- 27550179 TI - Crossover-site sequence and DNA torsional stress control strand interchanges by the Bxb1 site-specific serine recombinase. AB - DNA segment exchange by site-specific serine recombinases (SRs) is thought to proceed by rigid-body rotation of the two halves of the synaptic complex, following the cleavages that create the two pairs of exchangeable ends. It remains unresolved how the amount of rotation occurring between cleavage and religation is controlled. We report single-DNA experiments for Bxb1 integrase, a model SR, where dynamics of individual synapses were observed, using relaxation of supercoiling to report on cleavage and rotation events. Relaxation events often consist of multiple rotations, with the number of rotations per relaxation event and rotation velocity sensitive to DNA sequence at the center of the recombination crossover site, torsional stress and salt concentration. Bulk and single-DNA experiments indicate that the thermodynamic stability of the annealed, but cleaved, crossover sites controls ligation efficiency of recombinant and parental synaptic complexes, regulating the number of rotations during a breakage religation cycle. The outcome is consistent with a 'controlled rotation' model analogous to that observed for type IB topoisomerases, with religation probability varying in accord with DNA base-pairing free energies at the crossover site. Significantly, we find no evidence for a special regulatory mechanism favoring ligation and product release after a single 180 degrees rotation. PMID- 27550180 TI - Mitochondrial DNA exhibits resistance to induced point and deletion mutations. AB - The accumulation of somatic mitochondrial DNA (mtDNA) mutations contributes to the pathogenesis of human disease. Currently, mitochondrial mutations are largely considered results of inaccurate processing of its heavily damaged genome. However, mainly from a lack of methods to monitor mtDNA mutations with sufficient sensitivity and accuracy, a link between mtDNA damage and mutation has not been established. To test the hypothesis that mtDNA-damaging agents induce mtDNA mutations, we exposed MutaTMMouse mice to benzo[a]pyrene (B[a]P) or N-ethyl-N nitrosourea (ENU), daily for 28 consecutive days, and quantified mtDNA point and deletion mutations in bone marrow and liver using our newly developed Digital Random Mutation Capture (dRMC) and Digital Deletion Detection (3D) assays. Surprisingly, our results demonstrate mutagen treatment did not increase mitochondrial point or deletion mutation frequencies, despite evidence both compounds increase nuclear DNA mutations and demonstrated B[a]P adduct formation in mtDNA. These findings contradict models of mtDNA mutagenesis that assert the elevated rate of mtDNA mutation stems from damage sensitivity and abridged repair capacity. Rather, our results demonstrate induced mtDNA damage does not readily convert into mutation. These findings suggest robust mitochondrial damage responses repress induced mutations after mutagen exposure. PMID- 27550181 TI - Multipronged regulatory functions of a novel endonuclease (TieA) from Helicobacter pylori. AB - Helicobacter pylori portrays a classical paradigm of persistent bacterial infections. A well balanced homeostasis of bacterial effector functions and host responses is purported to be the key in achieving long term colonization in specific hosts. H. pylori nucleases have been shown to assist in natural transformation, but their role in virulence and colonization remains elusive. Therefore, it is imperative to understand the involvement of these nucleases in the pathogenesis of H. pylori Here, we report the multifaceted role of a TNFR-1 interacting endonuclease A (TieA) from H. pylori. tieA expression is differentially regulated in response to environmental stress and post adherence to gastric epithelial cells. Studies with isogenic knockouts of tieA revealed it to be a secretory protein which translocates into the host gastric epithelial cells independent of a type IV secretion system, gets phosphorylated by DNA-PK kinase and auto-phosphorylates as serine kinase. Furthermore, TieA binds to and cleaves DNA in a non-specific manner and promotes Fas mediated apoptosis in AGS cells. Additionally, TieA induced pro-inflammatory cytokine secretion via activation of transcription factor AP-1 and signaled through MAP kinase pathway. Collectively, TieA with its multipronged and moonlighting functions could facilitate H. pylori in maintaining a balance of bacterial adaptation, and elimination by the host responses. PMID- 27550182 TI - Characteristics of bone turnover markers in rapidly destructive coxopathy. AB - The purpose of this study was to clarify bone turnover marker levels in rapidly destructive coxopathy (RDC). Twenty patients with RDC (mean age, 72 +/- 11 years; 3 men, 17 postmenopausal women), 111 with osteoarthritis (OA) (age, 60 +/- 10 years; 15 men, 13 premenopausal women, 83 postmenopausal women), and 18 with osteonecrosis of femoral head (ON) (55 +/- 14 years; 11 men, 3 premenopausal women, 4 postmenopausal women), and 100 patients with femoral neck fracture (FNF) (81 +/- 10 years; 27 men, 73 postmenopausal women) were included. Serum tartrate resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), matrix metalloproteinase-3 (MMP-3) levels, and bone mineral density (BMD) of proximal femur and lumbar spine were investigated. TRACP-5b levels were significantly higher in RDC than in OA and ON, whereas BAP levels were higher in RDC than in OA (P < 0.05). MMP-3 levels were higher in RDC and ON than in OA (P < 0.05). TRACP 5b were higher in RDC than OA (P < 0.05) and FNF (P < 0.05) in performing propensity score matching; there were no differences in BMD between RDC and OA. TRACP-5b showed the largest area under the curve (AUC, 0.82) according to receiver operating characteristic (ROC) curve analysis for diagnosing RDC against OA and ON. AUCs of BAP and MMP-3 were 0.78 and 0.74. The respective sensitivities and specificities were 70.0 % and 85.3 % for TRACP-5b (cutoff, 623 mU/dl), 95.0 % and 57.1 % for BAP (13.8 U/l), and 70.0 % and 76.4 % for MMP-3 (52.7 ng/ml). The lack of differences in BMD suggested that high bone turnover marker levels may reflect osteoclast cell activation in RDC hips. Serum TRACP-5b and BAP could be RDC markers. PMID- 27550183 TI - Improving access to exercise training programs for patients with serious mental illness. AB - In a recent issue of this journal, Pratt et al report on an important new position statement by the Society of Behavioral Medicine and the American College of Sports Medicine to improve access to exercise programming as a treatment for patients treated in community mental health settings. If implemented, these recommendations could greatly expand access to these services and improve outcomes for patients treated in community mental health settings. PMID- 27550184 TI - Evaluation of the anti-fatigue effects of a traditional herbal drug, Gongjin-dan, under insufficient sleep conditions: study protocol for a randomised controlled trial. AB - BACKGROUND: Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans. METHODS/DESIGN: To investigate the anti fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase. DISCUSSION: This study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue. TRIAL REGISTRATION: Korean National Clinical Trial Registry CRIS; KCT0001681 , registered on 29 October 2015. PMID- 27550186 TI - Hemodynamic changes in cortical sensorimotor systems following hand and orofacial motor tasks and pulsed pneumotactile stimulation. AB - We performed a functional near-infrared spectroscopy (fNIRS) study of the evoked hemodynamic responses seen in hand and face sensorimotor cortical representations during (1) active motor tasks and (2) pulsed pneumotactile stimulation. Contralateral fNIRS measurements were performed on 22 healthy adult participants using a block paradigm that consisted of repetitive right hand and right oral angle somatosensory stimulation using a pulsed pneumotactile array stimulator, and repetitive right-hand grip compression and bilabial compressions on strain gages. Results revealed significant oxyhemoglobin (HbO) modulation across stimulus conditions in corresponding somatotopic cortical regions. Of the 22 participants, 86% exhibited a decreased HbO response during at least one of the stimulus conditions, which may be indicative of cortical steal, or hypo oxygenation occurring in channels adjacent to the primary areas of activation. Across all conditions, 56% of participants' HbO responses were positive and 44% were negative. Hemodynamic responses most likely differed across hand and face motor and somatosensory cortical regions due to differences in regional arterial/venous anatomy, cortical vascular beds, extent and orientation of somatotopy, task dynamics, and mechanoreceptor typing in hand and face. The combination of optical imaging and task conditions allowed for non-invasive examination of hemodynamic changes in somatosensory and motor cortices using natural, pneumatic stimulation of glabrous hand and hairy skin of the lower face and functionally relevant and measurable motor tasks involving the same structures. PMID- 27550187 TI - Piscinibacter defluvii sp. nov., isolated from a sewage treatment plant, and emended description of the genus Piscinibacter Stackebrandt et al. 2009. AB - A Gram-staining-negative, strictly aerobic bacterium, designated SH-1T, was isolated from activated sludge in Korea. Cells were motile rods with a single polar flagellum, showing oxidase-positive and catalase-negative activities. Growth was observed at 25-40 degrees C (optimum, 37 degrees C), pH 6.0-9.5 (optimum, pH 7.0) and with 0-0.5 % (w/v) NaCl (optimum, 0 %). Strain SH-1T contained summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0, C12 : 0, summed feature 8 (comprising C18 : 1omega7c and/or C18 : 1omega6c) and C10 : 0 3-OH as the major fatty acids and ubiquinone-8 as the sole isoprenoid quinone. Phosphatidylethanolamine was the major polar lipid, and diphosphatidylglycerol, phosphatidylglycerol, one aminophospholipid, one phospholipid, five unidentified aminolipids and two unidentified lipids were also detected as the minor polar lipids. The predominant polyamines were 2 hydroxyputrescine, cadaverine and putrescine. The DNA G+C content was 69.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SH-1T formed a tight phyletic lineage with Piscinibacter aquaticus IMCC1728T with a 98.3 % sequence similarity. However, the DNA-DNA relatedness value between strain SH-1T and the type strain of P. aquaticus was 38.0+/-1.8 %. On the basis of phenotypic, chemotaxonomic and molecular properties, it is clear that strain SH 1T represents a novel species of the genus Piscinibacter, for which the name Piscinibacter defluvii sp. nov. is proposed. The type strain is SH-1T (=KACC 18594T=JCM 31230T). An emended description of the genus Piscinibacter is also proposed. PMID- 27550185 TI - Evaluation of left atrial function in patients with iron-deficiency anemia by two dimensional speckle tracking echocardiography. AB - BACKGROUND: Iron-deficiency anemia (IDA) is a global health problem and a common medical condition that can be seen in everyday clinical practice. And two dimensional speckle tracking echocardiography (2D-STE) has been reported very useful in evaluating left atrial (LA) function, as well as left ventricular (LV) function. The aim of our study is to evaluate the LA function in patients with IDA by 2D-STE. METHODS: 65 patients with IDA were selected. This group of patients was then divided into two groups according to the degree of hemoglobin: group B (Hb > 90 g/L) and group C (Hb60 ~ 90 g/L). Another 30 healthy people were also selected as control group A. Conventional echocardiography parameters, such as left atrial diameter (LAD), peak E and A of mitralis (E, A), E/A, end diastolic thickness of ventricular septum (IVST d), end-diastolic thickness of LV posterior wall (PWTd) and left ventricular end-diastolic dimension (LVDd) were obtained from these three groups. Left atrial minimum volume (LAVmin), left atrial pre-atrial contraction volume (LAVp) and left atrial maximum volume (LAVmax) were measured by Simpson's rule, whereas left atrial active ejection fraction (LAAEF) and left atrial passive ejection fraction (LAPEF) were obtained from calculation. Two-dimensional images were acquired from apical four-chamber view and two-chamber view to store images for offline analysis. The global peak atrial longitudinal strain and strain rate of systolic LV (GLSs, GLSRs) as well as early and late diastolic LV strain rate (GLSRe, GLSRa) curves of LA were acquired in each LA segment from basal segment to top segment of LA by 2D-STE. RESULTS: Compared with group A, there were no differences between group B and group A (all P > 0.05). The LAAEF and GLSRa were significantly higher in group C compared with those of group A and group B (all P < 0.01). The LAPEF, GLSs, GLSRs and GLSRe were significantly lower in group C compared with those of group A and group B (all P < 0.01). CONCLUSIONS: 2D-STE could evaluate the LA function in patients with IDA. PMID- 27550188 TI - Role of anxiety and brooding in specificity of autobiographical recall. AB - Overgeneral schemas and lack of autobiographical memory (AM) specificity about our past experiences can predict mood disturbance. Rumination, functional avoidance and executive processes are the main explanatory variables of such overgenerality. However, in non-clinical samples, rumination predicts overgenerality most consistently after the induction of dysphoric mood. Anxiety also activates rumination. Furthermore, anxiety predicts memory performance and has effects on mood which are independent of the effects of rumination. So, what might be the role of anxiety in autobiographical memory performance? A sample of 210 voluntary participants reported measures of autobiographical memory, anxiety, rumination (brooding and reflection), functional avoidance and executive functions (semantic and phonetic verbal fluency task). Autobiographical performance (specificity) was negatively associated with brooding and age and positively with phonetic verbal fluency but not with functional avoidance and anxiety. However, anxiety and brooding were positively correlated even after controlling for depression scores. Moreover, using structural equation modeling, anxiety showed a significant indirect effect on autobiographical specificity through brooding rumination. These results suggest a possible association of anxiety with autobiographical recall through brooding rumination. PMID- 27550189 TI - [Erratum to: Flight and migration. A challenge for medicine in Germany]. PMID- 27550190 TI - Subsidence of total ankle component associated with deterioration of an ankle scale in non-inflammatory arthritis but not in rheumatoid arthritis. AB - OBJECTIVES: Modern three-component total ankle arthroplasty (TAA) has favorable clinical results and survival rates. However, radiographic deterioration and worsening of clinical symptoms may occur in patients with rheumatoid arthritis (RA) or non-inflammatory arthritis (NA). The associations between outcomes and clinical and radiological factors are not clear. We compared midterm clinical and radiographic outcomes after TAA between patients with RA and those with NA. METHODS: Twenty-six TAAs were performed using a three-component prosthesis, the FINE Total Ankle System during the study period. Fourteen TAAs with 11 RA patients undergoing primary TAA were compared with twelve TAAs with 12 NA patients. Clinical and radiographic outcomes were evaluated before and after operation, and at the final follow-up. RESULTS: The Japanese Society for Surgery of the Foot (JSSF) scale improved significantly following TAA in both groups (p = 0.0039 and 0.0156, respectively). Tibial subsidence, talar subsidence and age were significantly associated with postoperative JSSF score only in the NA group (p = 0.0027, 0.0017 and p < 0.0001, respectively). Stepwise regression analysis showed that talar subsidence was an independent predictor of a worse JSSF score in the NA group (F = 10.3). CONCLUSIONS: The final clinical outcome was negatively influenced by talar subsidence in patients with NA, but not in those with RA. PMID- 27550191 TI - Elucidating Proton Involvement in the Rate-Determining Step for Pt/Pd-Based and Non-Precious-Metal Oxygen Reduction Reaction Catalysts Using the Kinetic Isotope Effect. AB - The development of non-precious-metal (NPM) catalysts to replace the Pt alloys currently used in fuel cells to facilitate the oxygen reduction reaction (ORR) is a vital step in the widespread utilization of fuel cells. Currently, the ORR mechanism for NPM catalysts is not well understood, prohibiting the design and preparation of improved NPM catalysts. We conducted a kinetic isotope effect (KIE) study to identify the rate-determining step (RDS) of this intricate electrocatalytic reaction involving multiple proton-coupled electron transfer (PCET) processes. We observed a KIE of about 2 for the ORR catalyzed by a NPM catalyst, which demonstrates that for these electrocatalysts protons are involved in the RDS during ORR. These results contribute to a more complete understanding of the ORR mechanism and suggest that the design of future NPM catalysts must include careful consideration of the role of protons during ORR. PMID- 27550192 TI - David Oliver: Wishful thinking won't save the NHS. PMID- 27550194 TI - Molecular E(CN)3 (E=Sb, Bi) Species Synthesized from Ionic Liquids as Solvates. AB - The heavy pnictogen tricyanides, E(CN)3 (E=Sb, Bi), were synthesized from EF3 and Me3 SiCN in ionic liquids, for example, 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIm][OTf]), which prevents the oligomerization of the molecular E(CN)3 species by formation of [BMIm][E(CN)3 (OTf)] salts in solution. Recrystallization of [BMIm][E(CN)3 (OTf)] from THF led to the isolation and full characterization of the molecular species E(CN)3 ?2 THF. PMID- 27550193 TI - High-fat diet disrupts metabolism in two generations of rats in a parent-of origin specific manner. AB - Experimental and epidemiological evidence demonstrate that ancestral diet might contribute towards offspring health. This suggests that nutrition may be able to modify genetic or epigenetic information carried by germ cells (GCs). To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). At 19 weeks, founders (F0) were bred with controls, establishing the F1 generation. HFD resulted in 9.7% and 14.7% increased weight gain in male and female F0 respectively. F1 offspring of HFD mothers and F1 daughters of HFD-fed fathers had increased weight gain compared to controls. F1 rats were bred with controls at 19 weeks to generate F2 offspring. F2 male offspring derived from HFD-fed maternal grandfathers exhibited increased adiposity, plasma leptin and luteinising hormone to testosterone ratio. Despite transmission via the founding male germline, we did not find significant changes in the F0 intra-testicular GC transcriptome. Thus, HFD consumption by maternal grandfathers results in a disrupted metabolic and reproductive hormone phenotype in grandsons in the absence of detectable changes in the intra-testicular GC transcriptome. PMID- 27550195 TI - Introduction of H-antigens into oligosaccharides and sugar chains of glycoproteins using highly efficient 1,2-alpha-l-fucosynthase. AB - Fucalpha1-2 Gal linkages, or H-antigens, constitute histo-blood group antigens and are involved in various physiological processes. In addition, recent studies have shown that the H-antigen-containing glycans play an important role, not only in establishing harmonious relationship between gut microbes and the host, but also in preventing gut dysbiosis-related diseases. Therefore, development of an efficient method for introducing Fuc residue at Gal residue at the nonreducing end of glycans via alpha-(1->2) linkage is desired for research as well as medicinal purposes. In this study, we succeeded in derivatizing inverting 1,2 alpha-l-fucosidase (AfcA) into a highly efficient 1,2-alpha-l-fucosynthase. The synthase specifically synthesized H type 1-, type 2-, type 3- and type 4-chain containing oligosaccharides with yields of 57-75% based on acceptor depletion. The synthase was also able to specifically introduce Fuc residues into Lewis a/x antigens to produce Lewis b/y antigens, with yields of 43% and 62%, respectively. In addition, the enzyme efficiently introduced H-antigens into sugar chains of porcine gastric mucins, as revealed by lectin blotting and mass spectroscopy analysis of the sugars. Detailed acceptor specificity analysis using various monosaccharides and oligosaccharides unraveled unique substrate recognition feature of this synthase at the subsite (+1), which can be explained by our previous X-ray crystallographic study of AfcA. These results show that the synthase developed in this study could serve as an alternative to other H-antigen synthesis methods involving alpha-1,2-fucosyltransferases and retaining alpha fucosidase. PMID- 27550196 TI - Modification of linear (beta1->3)-linked gluco-oligosaccharides with a novel recombinant beta-glucosyltransferase (trans-beta-glucosidase) enzyme from Bradyrhizobium diazoefficiens. AB - Recently, we have shown that glycoside hydrolases enzymes of family GH17 from proteobacteria (genera Pseudomonas, Azotobacter) catalyze elongation transfer reactions with laminari-oligosaccharides generating (beta1->3) linkages preferably and to a lesser extent (beta1->6) or (beta1->4) linkages. In the present study, the cloning and characterization of the gene encoding the structurally very similar GH17 domain of the NdvB enzyme from Bradyrhizobium diazoefficiens, designated Glt20, as well as its catalytic properties are described. The Glt20 enzyme was strikingly different from the previously investigated bacterial GH17 enzymes, both regarding substrate specificity and product formation. The Azotobacter and Pseudomonas enzymes cleaved the donor laminari-oligosaccharide substrates three or four moieties from the non-reducing end, generating linear oligosaccharides. In contrast, the Glt20 enzyme cleaved donor laminari-oligosaccharide substrates two glucose moieties from the reducing end, releasing laminaribiose and transferring the remainder to laminari oligosaccharide acceptor substrates creating only (beta1->3)(beta1->6) branching points. This enables Glt20 to transfer larger oligosaccharide chains than the other type of bacterial enzymes previously described, and helps explain the biologically significant formation of cyclic beta-glucans in B. diazoefficiens. PMID- 27550197 TI - Transcript Levels of Androgen Receptor Variant 7 and Ubiquitin-Conjugating Enzyme 2C in Hormone Sensitive Prostate Cancer and Castration-Resistant Prostate Cancer. AB - PURPOSE: This study is designed to identify the androgen receptor variant 7 (AR V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy. METHODS: We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC. We examined associations between mRNA expression of AR-V7 and clinicopathologic factors. Furthermore, to identify other potential genes involved in the development of CRPC, RNA sequencing was conducted, using paired prostate cancer (PCa) tissues obtained immediately prior to treatment and at the time of therapeutic resistance. RESULTS: A total of 13 HSPC patients and three CRPC patients were enrolled. Neither a high Gleason score (score of 8 and 9) nor a high risk of PCa (a high risk of locally advanced PCa according to NCCN guidelines) was correlated with mRNA expression of AR-V7 in HSPC (P = 0.153 and P = 0.215). The mRNA expression of AR-FL, but not AR-V7, was significantly associated with the mRNA expression of UBE2C level in HSPC (P = 0.007). However, increased expression of AR-V7, not AR-FL, paralleled increased expression of UBE2C in the CRPC specimens (P = 0.03). AR-V7 expression status before ADT was likely related to shorter CRPC development in patients treating ADT. The result of the RNA-sequencing analysis using serial samples from the same patient before and after castration demonstrated an increased level of the PI3K regulatory subunit 1 (P = 0.018). CONCLUSION: Our study revealed the role of UBE2C as a marker of the androgen signaling pathway in PCa. Differential gene expression analysis using serial samples from the same patient before and after castration revealed potential genes and pathways involved in development of CRPC. Further studies are needed to determine whether these genes and pathways are potential therapeutic target for CRPC. Prostate 77:60-71, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27550198 TI - Site Directed Mutagenesis of Dextransucrase DsrM from Weissella cibaria: Transformation to a Reuteransucrase. AB - Glucansucrases produce alpha-glucans and gluco-oligosaccharides; the linkage type and molecular weight of glucans impacts their functionality. This study compared the catalytic specificities of dextransucrase DsrM from Weissella cibaria 10M and derivatives of this enzymes with GtfA from Lactobacillus reuteri TMW1.656. The N variable region, which is dispensable for GtfA activity, was essential for DsrM activity. Parallel amino acid substitutions in DsrM-DeltaS and GtfA-DeltaN indicated that the acceptor binding site residues determining the linkage type differ in these enzymes. DsrM-V583P:V586I had comparable enzyme activity as the respective GtfA derivative but did not increase the proportion of alpha-(1->4) linkages. DsrM-S622N had low enzyme activity and an unaltered proportion of alpha (1->4) linkages while the analogous GtfA-S1062N maintained enzyme activity but increased the proportion of alpha-(1->4) linkages. This study of dextransucrase from Weissella spp. thus elucidated differences between glucansucrases and will facilitate study of the structure-function relationships of dextran and isomalto oligosaccharides. PMID- 27550199 TI - New Screening Criteria Setting on Evaluation of Cytochrome P450 Induction Using HepaRG Cells with Multiplex Branched DNA Technologies in Early Drug Discovery. AB - BACKGROUND: Cytochrome P450 (CYP) enzymes are induced by some therapeutic drugs, leading to interactions reducing drug plasma concentrations. Recently, an assessment of CYP induction using messenger RNA (mRNA) levels has shown advantages over measurement of enzymatic activity; it has a larger dynamic range of induction and enables us to measure the intrinsic induction potential of time dependent CYP inhibitors. In order to minimize the late-stage attrition of new chemical entities (NCE), it is important to evaluate CYP induction potency at mRNA levels in the early stage of drug development. OBJECTIVES: The aim of this study is to establish a new screening method to evaluate induction potency of CYP1A2, CYP2B6, and CYP3A4 at mRNA levels. METHODS: QuantiGene Plex 2.0 Assay using HepaRG cells. RESULTS: The results from our new CYP induction assay system corresponded well to the already reported results obtained by using human hepatocytes. The induction potency was evaluated by calculating the concentration of test compounds that gives 10% of positive control response (R10), which is measurable even when full dose-response curves cannot be obtained. Compared with the evaluation of CYP induction in human hepatocytes, the response at R10 in HepaRG cells suggested the possibility of exhibiting induction potency for corresponding CYPs. Interestingly, the results with our in-house 109 compounds showed that several compounds induced CYP1A2 or CYP2B6 expression without upregulation of CYP3A4. CONCLUSION: Our developed assay system, as well as the R10 value, is useful for evaluating the CYP induction potency of NCE in early drug discovery. PMID- 27550200 TI - Fungal vincristine from Eutypella spp - CrP14 isolated from Catharanthus roseus induces apoptosis in human squamous carcinoma cell line -A431. AB - BACKGROUND: Catharanthus roseus, a medicinal plant, is known to produce secondary metabolites, vincristine and vinblastine, which are terpenoid indole alkaloids. Previously we have reported that Eutypella spp - CrP14 isolated from stem cutting of this plant had shown significant antiproliferative activity when tested in vitro against HeLa cell line. The present study was conducted to identify the anticancer compound responsible for the anti-proliferative activity of the fungal extract and to evaluate its in vitro anticancer and apoptotic effects. METHODS: The anti-proliferative activity of the fungal anticancer compound, vincristine was analyzed by MTT assay against different cancer cell lines. We examined its efficacy of apoptotic induction on A431 cells. The parameters examined included cell cycle distribution, loss of mitochondrial membrane potential (MMP), DNA fragmentation and reactive oxygen species (ROS) generation. RESULTS: The presence of vincristine in fungal culture filtrate was confirmed through chromatographic and spectroscopic analyses, and the amount was estimated to be 53 +/- 5.0 MUg/l. The partially purified fungal vincristine had strong cytotoxic activity towards human squamous carcinoma cells - A431 in the MTT assay. Furthermore, we showed that the fungal vincristine was capable of inducing apoptosis in A431 cells through generation of reactive oxygen species and activation of the intrinsic pathway leading to loss of MMP. CONCLUSIONS: We have demonstrated for the first time that the vincristine from Eutypella spp - CrP14 is an efficient inducer of apoptosis in A431 cells, meriting its further evaluation in vivo. PMID- 27550201 TI - Xanthoma-like multiple yellowish nodular colloid degeneration on the face and scalp. PMID- 27550202 TI - The Role of Autophagy in Rheumatic Disease. AB - Autophagy is an evolutionarily conserved degradation process in triggered by metabolic stress or environmental changes. Autophagy involves formation of autophagosomes, which fuse with lysosomes and degrade encapsulated intracellular components, such as long-lived and misfolded proteins, as well as intracellular organelles. Autophagy has been implicated in a wide variety of physiological and pathological conditions, and was recently implicated in the regulation of immunity and inflammation. Rheumatic diseases are a group of disorders characterized by immune system malfunctions in which the body attacks its own tissues. These diseases can seriously threaten human health if untreated. Although the underlying pathophysiology of autoimmune diseases has not yet been fully elucidated, autophagy has been implicated in their progression. In this article, we review the basics of autophagy, and the functional role of autophagy in the pathogenesis of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Crohn's disease and ankylosing spondylitis (AS). Moreover, we reviewed the role of autophagy and autophagy-related genes (Atgs) in innate and adaptive immunity, as well as the pathogenic crosstalk between autophagy and apoptosis. Our findings should provide valuable insights into the role of autophagy in the pathogenesis of rheumatic diseases. In addition, identification of novel autophagy-associated target proteins may offer a promising target for drugs treating human rheumatic disorders. PMID- 27550203 TI - beta-cell differentiation status in type 2 diabetes. AB - Type 2 diabetes (T2D) affects 415 million people worldwide and is characterized by chronic hyperglycaemia and insulin resistance, progressing to insufficient insulin production, as a result of beta-cell failure. Over time, chronic hyperglycaemia can ultimately lead to loss of beta-cell function, leaving patients insulin-dependent. Until recently the loss of beta-cell mass seen in T2D was considered to be the result of increased rates of apoptosis; however, it has been proposed that apoptosis alone cannot account for the extent of beta-cell mass loss seen in the disease, and that a loss of function may also occur as a result of changes in beta-cell differentiation status. In the present review, we consider current knowledge of determinants of beta-cell fate in the context of understanding its relevance to disease process in T2D, and also the impact of a diabetogenic environment (hyperglycaemia, hypoxia, inflammation and dyslipidaemia) on the expression of genes involved in maintenance of beta-cell identity. We describe current knowledge of the impact of the diabetic microenvironment on gene regulatory processes such alternative splicing, the expression of disallowed genes and epigenetic modifications. Elucidating the molecular mechanisms that underpin changes to beta-cell differentiation status and the concomitant beta-cell failure offers potential treatment targets for the future management of patients with T2D. PMID- 27550204 TI - Effect of Frail Phenotype on Bone Mass and Vertebral Compression Fracture in Individuals Undergoing Dialysis. PMID- 27550205 TI - Middle ear polyps: results of traction avulsion after a lateral approach to the ear canal in 62 cats (2004-2014). AB - Objectives The objective of this study was to report the surgical outcome and complication rate of deep traction avulsion (TA) of feline aural inflammatory polyps after a lateral approach (LA) to the ear canal. Methods This was a retrospective analysis of data retrieved from an electronic database of 62 cats treated with TA after an LA (TALA) for removal of ear canal polyps. Long-term outcome was assessed via a telephone questionnaire survey with the owners. Results Domestic shorthair cats (48%) and Maine Coons (37%) were over represented. The most common presenting clinical signs were otorrhoea, ear scratching and head shaking. Video-otoscopic examination confirmed a polypous mass in the ear canal in all patients. All 62 cats underwent TALA, with a mean surgical time of 33 mins for experienced surgeons (n = 4) and 48 mins (n = 12) for less experienced surgeons. The recurrence rate of polyp regrowth for experienced surgeons was 14.3% vs 35% for the less experienced surgeons. Postoperative complications included Horner's syndrome (11.5%) and facial nerve paralysis (3%). Otitis interna was not observed. Conclusions and relevance A lateral approach to the ear canal in combination with deep TA of an aural inflammatory polyp is an effective first-line technique that results in a low recurrence and complication rate. PMID- 27550206 TI - Male Mondor's Disease is a Rare Entity. PMID- 27550207 TI - Comparative Analysis of Deoxynivalenol Biosynthesis Related Gene Expression among Different Chemotypes of Fusarium graminearum in Spring Wheat. AB - Fusarium mycotoxins, deoxynivalenol (DON) and nivalenol (NIV) act as virulence factors and are essential for symptom development after initial infection in wheat. To date, 16 genes have been identified in the DON biosynthesis pathway. However, a comparative gene expression analysis in different chemotypes of Fusarium graminearum in response to Fusarium head blight infection remains to be explored. Therefore, in this study, nine genes that involved in trichothecene biosynthesis were analyzed among 3-acetyldeoxynivalenol (3-ADON), 15 acetyldeoxynivalenol (15-ADON) and nivalenol producing F. graminearum strains in a time course study. Quantitative reverse transcription polymerase chain reaction revealed that the expression of all examined TRI gene transcripts initiated at 2 days post-inoculation (dpi), peaked at three to four dpi and gradually decreased at seven dpi. The early induction of TRI genes indicates that presence of high levels of TRI gene transcripts at early stages is important to initiate the biosynthetic pathway of DON and NIV. Comparison of gene expression among the three chemotypes showed that relative expression of TRI genes was higher in 3 ADON producing strains compared with 15-ADON and NIV strains. Comparatively higher levels of gene expression may contribute to the higher levels of DON produced by 3-ADON strains in infected grains. PMID- 27550208 TI - Identification of Bremia lactucae and Oidium neolycopersici proteins extracted for intact spore MALDI mass spectrometric biotyping. AB - Several proteomic approaches were applied to identify protein markers providing typical signals during intact cell/spore (IC/IS) MALDI-TOF MS of two plant pathogens, namely Bremia lactucae (a downy mildew) and Oidium neolycopersici (a powdery mildew). First, proteins were extracted from intact spores of the microorganisms under conditions simulating their treatment prior to the mass spectrometric analysis. After a separation by electrophoresis and tryptic digestion, 198 and 140 proteins were identified in the B. lactucae and O. neolycopersici extracts, respectively. A large portion of them were found to be involved in the process of protein biosynthesis. For the first time, some proteins were assigned to characteristic signals in MS profiles of the investigated pathogens based on an agreement in the molecular mass. There were 9 and 10 proteins recognized, respectively, which could contribute significantly to the spectral patterns. These proteins were assigned tentatively to the following peaks in the MS profiles: (i) m/z 7828; 8593; 10 456; 11 312; 12 450; 12 763; 14 756 and 16 854 for B. lactucae; (ii) m/z 7709; 8895; 9504; 9952; 11 317; 14 082 and 14 839 for O. neolycopersici. We demonstrated the presence of ribosomal proteins and histones, which could be employed as markers in biotyping analyses for pathogen identification. PMID- 27550209 TI - Dietary Sodium Intake in Patients with Type 2 Diabetes Mellitus. PMID- 27550210 TI - Letter: Effects of Rebamipide on Gastrointestinal Symptoms in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2016;40:240-7). PMID- 27550211 TI - Response: Effects of Rebamipide on Gastrointestinal Symptoms in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2016;40:240-7). PMID- 27550212 TI - Multi-shot sensitivity-encoded diffusion data recovery using structured low-rank matrix completion (MUSSELS). AB - PURPOSE: To introduce a novel method for the recovery of multi-shot diffusion weighted (MS-DW) images from echo-planar imaging (EPI) acquisitions. METHODS: Current EPI-based MS-DW reconstruction methods rely on the explicit estimation of the motion-induced phase maps to recover artifact-free images. In the new formulation, the k-space data of the artifact-free DWI is recovered using a structured low-rank matrix completion scheme, which does not require explicit estimation of the phase maps. The structured matrix is obtained as the lifting of the multi-shot data. The smooth phase-modulations between shots manifest as null space vectors of this matrix, which implies that the structured matrix is low rank. The missing entries of the structured matrix are filled in using a nuclear norm minimization algorithm subject to the data-consistency. The formulation enables the natural introduction of smoothness regularization, thus enabling implicit motion-compensated recovery of the MS-DW data. RESULTS: Our experiments on in-vivo data show effective removal of artifacts arising from inter-shot motion using the proposed method. The method is shown to achieve better reconstruction than the conventional phase-based methods. CONCLUSION: We demonstrate the utility of the proposed method to effectively recover artifact free images from Cartesian fully/under-sampled and partial Fourier acquired data without the use of explicit phase estimates. Magn Reson Med 78:494-507, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27550213 TI - Elective or Emergency Use of Mechanical Circulatory Support Devices During Transcatheter Aortic Valve Replacement. AB - OBJECTIVE: Evaluate the use of mechanical circulatory support (MCS) devices in high-risk patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: The use of MCS devices in elderly patients with multiple comorbidities undergoing TAVR is underexplored. METHODS: All patients undergoing TAVR at a single tertiary academic center who required MCS during index procedure between 2008 and 2015 were included in a prospective database. RESULTS: MCS was used in 9.4% (54/577) of all TAVRs (n = 52 Edwards Sapien and n = 2 CoreValves) of which 68.5% (n = 37) were used as part of a planned strategy, and 31.5% (n = 17) were used in emergency "bail-out" situations. IABP was the most commonly used device (87%) followed by Impella and ECMO (6% each). Among the MCS group, 22% required cardiopulmonary resuscitation during the procedure (n = 4 elective [11%] vs. n = 8 emergent [47%]) and 15% upgrade to a second device (Impella or CPB after IABP; n = 5 elective [14%] vs. n = 3 emergent [18%]). Median duration of support was 1-day. Device related complications were low (4%). In-hospital mortality in this extremely high-risk population was 24% (13/54) (11% [4/37] for elective cases and 53% [9/17] for emergency cases). Cardiogenic shock (50%) was the most common cause of in-hospital death. Cumulative all-cause 1-year mortality was 35% (19/54) (19% 97/370 for elective and 71% [12/17] for emergency cases). CONCLUSION: Emergent use of MCS during TAVR in extremely high-risk population is associated with high short and long-term mortality rates. Early identification of patients at risk for hemodynamic compromise may rationalize elective utilization of MCS during TAVR. PMID- 27550214 TI - Post procedure headache in patients treated for neurovascular arteriovenous malformations and aneurysms using endovascular therapy. AB - BACKGROUND: Though endovascular therapy (EVT) is increasingly applied in the treatment of intracranial vascular lesions, little is known about the effect of EVT on post-procedure headache. We aimed to investigate the prevalence of headache in patients who have undergone EVT for cerebral arteriovenous malformations (AVMs) and aneurysms. METHODS: A total of 324 patients underwent EVT treatment for aneurysms and AVMs at the Danish National Hospital from January 2012 to December 2014. We applied strict exclusion criteria in order to minimize the effect of other factors on headache occurrence, e.g., craniotomy. Eligible subjects were phone-interviewed using a purpose-developed semi-structured questionnaire. Headaches were classified according to ICHD-III beta criteria. RESULTS: The 59 patients underwent treatment of aneurysms (n = 43), cranial dural fistulas (n = 11), and AVMs (n = 5). There was a significant increase in overall headache (p = 0.017) and tension-type headache (TTH) (p = 0.012) within the first 3 months after EVT compared to 1 month before EVT. However, at interview time (median 2.5 years post-EVT), the increase in overall headache, migraine, and tension-type headache was not statistically significant. A minority of patients experienced headaches for the first time within 3 months of their EVT (migraine 4, TTH 10). At interview time, 50 % of these new headaches still persisted. CONCLUSION: Our results suggest a temporary increase in headache in the first 3 months after EVT, which normalizes over time. Clinicians may use this knowledge to better inform their patients of functional outcomes after their EVT procedure. PMID- 27550215 TI - Programs of religious/spiritual support in hospitals - five "Whies" and five "Hows". AB - A contemporary orientation of the hospital experience model must encompass the clients' religious-spiritual dimension. The objective of this paper is to share a previous experience, highlighting at least five reasons hospitals should invest in this direction, and an equal number of steps required to achieve it. In the first part, the text discourses about five reasons to invest in religious spiritual support programs: 1. Religious-spiritual wellbeing is related to better health; 2. Religious-spiritual appreciation is a standard for hospital accreditation; 3. To undo religious-spiritual misunderstandings that can affect treatment; 4. Patients demand a religious-spiritual outlook from the institution; and 5. Costs may be reduced with religious-spiritual support. In the second part, the text suggests five steps to implement religious-spiritual support programs: 1. Deep institutional involvement; 2. Formal staff training; 3. Infrastructure and resources; 4. Adjustment of institutional politics; and 5. Agreement with religious-spiritual leaders. The authors hope the information compiled here can inspire hospitals to adopt actions toward optimization of the healing experience. PMID- 27550216 TI - Micellar liquid chromatographic determination of metformin hydrochloride using fluorimetric detection after pre-column derivatization: application to pharmacokinetic parameters in immediate and sustained release formulations. AB - An accurate and selective method using micellar liquid chromatography was developed to determine metformin hydrochloride both in its pharmaceutical dosage forms and human plasma. Separation was conducted using a Zorbax SB-Phenyl (250 * 4.6 mm id) stainless steel column at ambient temperature after pre-column derivatization with 9,10-phenanthraquinone. A mobile phase composed of 0.1 M sodium dodecyl sulfate, 10% 1-propanol and triethylamine (0.3%) in 0.02 M phosphoric acid, adjusted to pH 2.5, was used at a flow rate of 1 ml/min with fluorimetric detection at 450 nm after excitation at 306 nm. The proposed method showed high sensitivity with limit of quantification of 0.35 MUg/ml and limit of detection of 0.23 MUg/ml, being linear from 0.5 to 3.0 MUg/ml. Being highly sensitive, the method could be applied to spiked human plasma, and also to follow the pharmacokinetic parameters of the studied drug in healthy volunteers after administration of both its immediate and sustained release tablet formulations. Such procedures were carried out without any extraction steps, which improves the accuracy and precision of the proposed method when applied to human plasma. Detailed validation procedures were also carried out giving results in accordance with the comparison method. The proposed method has also the advantage of being environmentally safe, where the use of organic solvents is highly limited in comparison with other traditional chromatographic separation methods that depend mainly on a high proportion of organic modifiers. This concept, in turn, emphasizes the application of green chemistry in the analysis of pharmaceutical products. The simplicity, relatively low cost and short analysis time of the suggested method makes it a candidate for routine quality control work. PMID- 27550218 TI - Biological synthesis of nanosized sulfide semiconductors: current status and future prospects. AB - There have been extensive and comprehensive reviews in the field of metal sulfide precipitation in the context of environmental remediation. However, these works have focused mainly on the removal of metals from aqueous solutions-usually, metal-contaminated effluents-with less emphasis on the precipitation process and on the end-products, frequently centering on metal removal efficiencies. Recently, there has been an increasing interest not only in the possible beneficial effects of these bioremediation strategies for metal-rich effluents but also on the formed precipitates. These metal sulfide materials are of special relevance in industry, due to their optical, electronic, and mechanical properties. Hence, identifying new routes for synthesizing these materials, as well as developing methodologies allowing for the control of the shape and size of particulates, is of environmental, economic, and practical importance. Multiple studies have shown proof-of-concept for the biological synthesis of inorganic metallic sulfide nanoparticles (NPs), resorting to varied organisms or cell components, though this information has scarcely been structured and compiled in a systematic manner. In this review, we overview the biological synthesis methodologies of nanosized metal sulfides and the advantages of these strategies when compared to more conventional chemical routes. Furthermore, we highlight the possibility of the use of numerous organisms for the synthesis of different metal sulfide NPs, with emphasis on sulfate-reducing bacteria (SRB). Finally, we put in perspective the potential of these methodologies in the emerging research areas of biohydrometallurgy and nanobiotechnology for the uptake of metals in the form of metal sulfide nanoparticles. A more complete understanding of the principles underlying the (bio)chemistry of formation of solids in these conditions may lead to the large-scale production of such metal sulfides, while simultaneously allowing an enhanced control over the size and shape of these biogenic nanomaterials. PMID- 27550217 TI - Genome analysis and avirulence gene cloning using a high-density RADseq linkage map of the flax rust fungus, Melampsora lini. AB - BACKGROUND: Rust fungi are an important group of plant pathogens that cause devastating losses in agricultural, silvicultural and natural ecosystems. Plants can be protected from rust disease by resistance genes encoding receptors that trigger a highly effective defence response upon recognition of specific pathogen avirulence proteins. Identifying avirulence genes is crucial for understanding how virulence evolves in the field. RESULTS: To facilitate avirulence gene cloning in the flax rust fungus, Melampsora lini, we constructed a high-density genetic linkage map using single nucleotide polymorphisms detected in restriction site-associated DNA sequencing (RADseq) data. The map comprises 13,412 RADseq markers in 27 linkage groups that together span 5860 cM and contain 2756 recombination bins. The marker sequences were used to anchor 68.9 % of the M. lini genome assembly onto the genetic map. The map and anchored assembly were then used to: 1) show that M. lini has a high overall meiotic recombination rate, but recombination distribution is uneven and large coldspots exist; 2) show that substantial genome rearrangements have occurred in spontaneous loss-of-avirulence mutants; and 3) identify the AvrL2 and AvrM14 avirulence genes by map-based cloning. AvrM14 is a dual-specificity avirulence gene that encodes a predicted nudix hydrolase. AvrL2 is located in the region of the M. lini genome with the lowest recombination rate and encodes a small, highly-charged proline-rich protein. CONCLUSIONS: The M. lini high-density linkage map has greatly advanced our understanding of virulence mechanisms in this pathogen by providing novel insights into genome variability and enabling identification of two new avirulence genes. PMID- 27550219 TI - Opening the black box of transfer systems in public sector health services in a Western state in India. AB - BACKGROUND: Limited research on Posting and Transfer (P&T) policies and systems in the public sector health services and the reluctance for an open debate on the issue makes P&T as a black box. Limited research on P&T in India suggests that P&T policies and systems are either non-existent, weak, poorly implemented or characterized by corruption. Hence the current study aimed at opening the "black box" of P&T systems in public sector health services in India by assessing the implementation gaps between P&T policies and their actual implementation. METHODS: This was a qualitative study carried out in Department of Health, in a Western State in India. To understand the extant P&T policies, a systems map was first developed with the help of document review and Key Informant (KI) Interviews. Next systems audit was carried out to assess the actual implementation of transfer policies by interviewing Medical Officers (MOs), the group mainly affected by the P&T policies. Job histories were constructed from the interviews to understand transfer processes like frequencies of transfers and to assess if transfer rules were adhered. The analysis is based on a synthesis of document review, 19 in-depth interviews with MOs working with state health department and five in-depth interviews with Key Informants (KIs). Framework analysis approach was used to analyze data using NVIVO. RESULTS: The state has a generic transfer guideline applicable to all government officers but there is no specific transfer policy or guideline for government health personnel. The generic transfer guidelines are weakly implemented indicating a significant gap between policy and actual implementation. The formal transfer guidelines are undermined by a parallel system in which desirable posts are attained, retained or sometimes given up by the use of political connections and money. MOs' experiences of transfers were marked by perceptions of unfairness and irregularities reflected through interviews as well as the job histories. DISCUSSION: The generic transfer rules and ambiguity in how transfers are treated may explain the discrepancy between policy and implementation leading to systems abuse. This discrepancy could have negative influence on MOs' morale which could in turn affect distribution of MOs. Where possible, ambiguity in the rules should be avoided and a greater transparency on implementation of the transfer rules is needed. However, it may not be possible to make any significant improvements to P&T policies and how they are implemented until the external pressure that creates parallel systems is greatly reduced in translating HR policy into HR practice. CONCLUSIONS: Effective P&T policies and implementation may have important implications for organizational performance and may help to improve Human Resource (HR) policy and HR expertise. Also there is a greater need for transparency on implementation of the rules. However, it may not be possible to make any significant improvements to P&T policies and how they are implemented until the external pressure that creates parallel systems is greatly reduced. PMID- 27550220 TI - Congenital heart defects and left ventricular non-compaction in males with loss of-function variants in NONO. AB - BACKGROUND: The non-POU domain containing octamer-binding gene (NONO) is located on chromosome Xq13.1 and encodes a member of a small family of RNA-binding and DNA-binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Loss-of-function variants in NONO have been described as a cause of intellectual disability in males but have not been described in association with congenital heart defects or cardiomyopathy. In this article, we seek to further define the phenotypic consequences of NONO depletion in human subjects. METHODS: We searched a clinical database of over 6000 individuals referred for exome sequencing and over 60 000 individuals referred for CNV analysis. RESULTS: We identified two males with atrial and ventricular septal defects, left ventricular non-compaction (LVNC), developmental delay and intellectual disability, who harboured de novo, loss-of-function variants in NONO. We also identified a male infant with developmental delay, congenital brain anomalies and severe LVNC requiring cardiac transplantation, who inherited a single-gene deletion of NONO from his asymptomatic mother. CONCLUSIONS: We conclude that in addition to global developmental delay and intellectual disability, males with loss-of-function variants in NONO may also be predisposed to developing congenital heart defects and LVNC with the penetrance of these cardiac-related problems being influenced by genetic, epigenetic, environmental or stochastic factors. Brain imaging of males with NONO deficiency may reveal structural defects with abnormalities of the corpus callosum being the most common. Although dysmorphic features vary between affected individuals, relative macrocephaly is a common feature. PMID- 27550221 TI - Use of Bayesian Inference in Crystallographic Structure Refinement via Full Diffraction Profile Analysis. AB - A Bayesian inference method for refining crystallographic structures is presented. The distribution of model parameters is stochastically sampled using Markov chain Monte Carlo. Posterior probability distributions are constructed for all model parameters to properly quantify uncertainty by appropriately modeling the heteroskedasticity and correlation of the error structure. The proposed method is demonstrated by analyzing a National Institute of Standards and Technology silicon standard reference material. The results obtained by Bayesian inference are compared with those determined by Rietveld refinement. Posterior probability distributions of model parameters provide both estimates and uncertainties. The new method better estimates the true uncertainties in the model as compared to the Rietveld method. PMID- 27550222 TI - [Adjunctive corticosteroids for antimicrobial treatment]. PMID- 27550223 TI - [Adjunctive corticosteroid therapy for the treatment of keratitis should be assessed case by case]. PMID- 27550224 TI - [Diagnosis and treatment of episcleritis and scleritis]. AB - Episcleritis is a benign and self-limiting disease, often with a recurrent course, manifesting mainly in young adults. In less than a third of patients, an associated systemic disease can be found. In contrast, scleritis is observed mainly in patients between the 4th and 6th decade of life, may lead to severe ocular complications, and is often associated with a systemic rheumatological disease. Diffuse, nodular, and necrotizing forms of scleritis can be differentiated. Necrotizing and posterior scleritis have a higher risk of complications and worse visual outcome. In most cases, medical history and slit lamp examination allow differentiation of episcleritis and scleritis. Whereas episcleritis is treated mainly symptomatically with artificial tears, topical corticosteroids, and potentially with systemic nonsteroidal anti-inflammatory drugs, scleritis requires early and aggressive anti-inflammatory treatment in a stepwise approach. PMID- 27550226 TI - National survey of family physicians to define functional decline in elderly patients with minor trauma. AB - BACKGROUND: Failing to assess elderly patients for functional decline at the time around a minor injury may result in adverse health outcomes. This study was conducted to define what constitutes clinically significant functional decline and the sensitivity required for a clinical decision instrument to identify such functional decline after an injury in previously independent elderly patients. METHODS: After a thorough development process, a survey questionnaire was administered to a random sample of 178 family physicians. The surveys were distributed using a modified Dillman technique. RESULTS: From 143 eligible surveys, we received 67 completed surveys (response rate, 46.9 %). Respondents indicated that a drop of at least 3 points on the 28-point Older Americans Resources and Services (OARS) ADL Scale was considered clinically significant by 90 % of physicians. Ninety percent (90 %) of physicians would be satisfied with a sensitivity of 90 % or more for a clinical decision instrument to detect patients at risk of functional decline at 6 months following an injury. The majority of family physicians do not routinely assess the majority of the tasks on the OARS scale for injured elderly patients. CONCLUSIONS: A high proportion of physicians (90 %) would consider a drop of 3 points on the OARS ADL Scale as significant to define functional decline and would be satisfied with a sensitivity of 90 % for a clinical decision instrument to detect such a decline. Any instrument to identify patients at elevated risk for subsequent decline should consider these outcome measures to be clinically useful. PMID- 27550225 TI - Telomere shortening leads to an acceleration of synucleinopathy and impaired microglia response in a genetic mouse model. AB - Parkinson's disease is one of the most common neurodegenerative disorders of the elderly and ageing hence described to be a major risk factor. Telomere shortening as a result of the inability to fully replicate the ends of linear chromosomes is one of the hallmarks of ageing. The role of telomere dysfunction in neurological diseases and the ageing brain is not clarified and there is an ongoing discussion whether telomere shortening is linked to Parkinson's disease. Here we studied a mouse model of Parkinson's disease (Thy-1 [A30P] alpha-synuclein transgenic mouse model) in the background of telomere shortening (Terc knockout mouse model). alpha-synuclein transgenic mice with short telomeres (alphaSYN(tg/tg) G3Terc(-/ )) developed an accelerated disease with significantly decreased survival. This accelerated phenotype of mice with short telomeres was characterized by a declined motor performance and an increased formation of alpha-synuclein aggregates. Immunohistochemical analysis and mRNA expression studies revealed that the disease end-stage brain stem microglia showed an impaired response in alphaSYN(tg/tg) G3Terc(-/-) microglia animals. These results provide the first experimental data that telomere shortening accelerates alpha-synuclein pathology that is linked to limited microglia function in the brainstem. PMID- 27550227 TI - Effect and Safety of TNF Inhibitors in Immunoglobulin-Resistant Kawasaki Disease: a Meta-analysis. AB - Previous studies showed that tumor necrosis factor (TNF) inhibitors might decrease the rate of coronary artery abnormalities in pediatrics with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Therefore, we aimed to evaluate the effect and safety of TNF inhibitors in IVIG-resistant KD. We undertook a meta-analysis of clinical trials identified in systematic searches of PubMed, EMBASE, Cochrane Database, and Google scholar through May 2016. Five studies were included. Overall, rate of coronary artery aneurysm was comparable between groups (relative risk (RR), 1.05; 95 % confidence interval (95 % CI), 0.60 to 1.81; P = 0.87). No significant differences were recorded between groups in coronary artery Z scores (standardized mean difference (SMD), 0.27; 95 % CI, 0.30 to 0.85; P = 0.35). Meanwhile, TNF inhibitors were not associated with a significant decreased risk of treatment resistance compared with IVIG treatment (RR, 0.65; 95 % CI, 0.37 to 0.15; P = 0.14). However, days of fever was significantly reduced in the TNF inhibitor group (SMD, -0.66; 95 % CI, -0.90 to 0.41; P < 0.001). Additionally, risk of serious adverse events was similar between groups. Therefore, TNF inhibitors could shorten the duration of fever in IVIG-resistant KD. However, TNF inhibitors appear to have no cardioprotective effect in patients with IVIG-resistant KD. PMID- 27550228 TI - Immobilization of proline-specific endoprotease on nonporous silica nanoparticles functionalized with amino group. AB - Enzyme immobilization is believed to provide an excellent base for increasing environmental tolerance of enzyme and considerable period of time. In this work, a kind of nonporous silica nanoparticles functionalized with amino group was synthesized to immobilize proline-specific endoprotease (PSEP). PSEP is known to specifically cleave peptides (or esters) at the carboxyl side of proline, thus can prevent the formation of haze and prolong the shelf life of beer. After immobilization, the environmental tolerance (temperature and pH, respectively) was obviously improved, and the immobilized enzyme can retain above 90 % of its original activity after 6 uses. Moreover, the immobilized enzyme can effectively prevent the formation of chill-haze using fresh beer fermentation liquid. PMID- 27550229 TI - Prediction and inhibition of the N2O accumulation in the BioDeNO x process for NO x removal from flue gas. AB - BioDeNO x process, which combines the advantages of the chemical absorption and biological reduction processes, is regarded as a promising candidate for NO removal from the flue gas. In the BioDeNO x , N2O was accumulated in the process of the biological reduction of FeII(EDTA)-NO. In this work, the pathway of the FeII(EDTA)-NO reduction was investigated and a mathematic model was developed to evaluate and predict the accumulation of N2O. Furthermore, parametric tests such as the effects of the C/N ratio (molar ratio of carbon/nitrogen), electron donor, and sulfite concentrations on N2O accumulation were investigated. Experimental results revealed that N2O accumulation was inhibited with a high C/N ratio (2.4), sufficient electron donor, and a low sulfite concentration. In addition, compared with the inorganic electron donor (FeII(EDTA)), the organic electron donor (glucose) was beneficial for microorganism metabolism and N2O accumulation inhibition. This work will provide significant insight into the inhibition of N2O accumulation during the operation of BioDeNO x and advance this novel process for the industrial application. PMID- 27550230 TI - A rare cutaneous adnexal neoplasm: cystic panfolliculoma. AB - A cystic panfolliculoma is a benign follicular neoplasm which recapitulates several portions of the hair follicle. The patient was a 64-year-old Caucasian female who presented with a new growth on her right forearm. The lesion had slowly enlarged over the previous 11 months. She complained of it bleeding on several occasions and being very tender when touched. On exam was an 8 mm firm pink papule which appeared slightly eroded. The growth was excised in clinic. Histology showed a well-circumscribed neoplasm with foci of matrical, infundibular, inner and outer root sheath differentiation. A BerEp3 labeled focal areas of follicular germinative differentiation at the periphery of the proliferation. The lesion was narrowly excised in the available planes of section. The surgical site healed well and there are no residual symptoms from the tumor. PMID- 27550232 TI - Urinary L-FABP as a marker of vesicoureteral reflux in children: could it also have a protective effect on the kidney? AB - PURPOSE: Liver-type fatty acid-binding protein is a small cytoplasmic protein which is expressed in the human renal proximal tubular epithelium and synthesized in response to renal tubular injury. The aim of the present study was to investigate the importance of urinary liver-type fatty acid-binding protein levels in children who diagnosed with vesicoureteral reflux. METHODS: Fifty-six patients with vesicoureteral reflux and 51 healthy controls were enrolled to the study. The cases were divided into three groups as follows: group A-the controls, group B-the patients who had renal parenchymal scarring and group C-the patients who had no scarring. Urinary liver-type fatty acid-binding protein was measured by enzyme-linked immunosorbent assay method. Creatinine was measured by modified Jaffe method, protein was measured by turbidimetric method, and urine density was determined by using the "falling drop" procedure. RESULTS: Urinary liver-type fatty acid-binding protein and urinary liver-type fatty acid-binding protein/creatinine levels were significantly higher in the whole patient group than in the controls (p = 0.016, 0.006). Significant differences were also determined by comparing the three groups (p = 0.015, 0.014), and those levels were found as significantly higher in group C. CONCLUSION: Urinary liver-type fatty acid-binding protein was considered to be helpful for the diagnosis of vesicoureteral reflux, and also it might contribute to understand the mechanisms causing scar tissue formation especially for the patients who had vesicoureteral reflux. Further clinical and experimental investigations are required to elucidate in detail the physiology of liver-type fatty acid-binding protein. PMID- 27550231 TI - Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling. AB - Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects. PMID- 27550233 TI - Information needs of oncologists, general practitioners and other professionals caring for patients with cancer. AB - Oncology is a rapidly developing field with a growing number of publications every year. The main goal of this survey was to learn more about the information needs of oncologists and general practitioners. Data were collected using a standardised questionnaire developed in collaboration with the German Cancer Society (Deutsche Krebsgesellschaft) and the German Association of General Practitioners (Deutscher Hausarzteverband). A total of 495 questionnaires could be evaluated. Medical congresses were the preferred source of information for all participants. General practitioners preferred textbooks, while oncologists preferred journals and the Internet (all p < .001). Reasons for a lack of confidence during patient consultation were lack of time (60% of participants), lack of knowledge (61% of general practitioners and 26% of oncologists) and lack of data (>50%). Oncologists felt more confident in searching scientific databases than general practitioners did. Both groups required rapid access to transparent information. For general practitioners, reviews and comments by experts helped to put new information in the context of cancer treatment. Oncologists and general practitioners showed significantly different information needs and different ways to access specific information. In order to better integrate general practitioners while simultaneously serving the needs of oncologists, a database that is up to date, rapidly accessible and does not incur high costs would be helpful. PMID- 27550235 TI - ZnO Luminescence and scintillation studied via photoexcitation, X-ray excitation, and gamma-induced positron spectroscopy. AB - The luminescence and scintillation properties of ZnO single crystals were studied by photoluminescence and X-ray-induced luminescence (XRIL) techniques. XRIL allowed a direct comparison to be made between the near-band emission (NBE) and trap emissions providing insight into the carrier recombination efficiency in the ZnO crystals. It also provided bulk luminescence measurements that were not affected by surface states. The origin of a green emission, the dominant trap emission in ZnO, was then investigated by gamma-induced positron spectroscopy (GIPS) - a unique defect spectroscopy method that enables positron lifetime measurements to be made for a sample without contributions from positron annihilation in the source materials. The measurements showed a single positron decay curve with a 175 ps lifetime component that was attributed to Zn vacancies passivated by hydrogen. Both oxygen vacancies and hydrogen-decorated Zn vacancies were suggested to contribute to the green emission. By combining scintillation measurements with XRIL, the fast scintillation in ZnO crystals was found to be strongly correlated with the ratio between the defect luminescence and NBE. This study reports the first application of GIPS to semiconductors, and it reveals the great benefits of the XRIL technique for the study of emission and scintillation properties of materials. PMID- 27550234 TI - Heterogeneous reduction of carbon dioxide by hydride-terminated silicon nanocrystals. AB - Silicon constitutes 28% of the earth's mass. Its high abundance, lack of toxicity and low cost coupled with its electrical and optical properties, make silicon unique among the semiconductors for converting sunlight into electricity. In the quest for semiconductors that can make chemicals and fuels from sunlight and carbon dioxide, unfortunately the best performers are invariably made from rare and expensive elements. Here we report the observation that hydride-terminated silicon nanocrystals with average diameter 3.5 nm, denoted ncSi:H, can function as a single component heterogeneous reducing agent for converting gaseous carbon dioxide selectively to carbon monoxide, at a rate of hundreds of MUmol h(-1) g( 1). The large surface area, broadband visible to near infrared light harvesting and reducing power of SiH surface sites of ncSi:H, together play key roles in this conversion. Making use of the reducing power of nanostructured hydrides towards gaseous carbon dioxide is a conceptually distinct and commercially interesting strategy for making fuels directly from sunlight. PMID- 27550236 TI - Kuopio University Hospital Job Satisfaction Scale (KUHJSS): its validation in the Greek language. AB - AIM: Tauranslation and validation of the Kuopio University Hospital Job Satisfaction Scale. BACKGROUND: Nurses' job satisfaction is crucial for the smooth functioning of the health-care system. METHODS: A Greek translation of the scale was made and administered to 126 psychiatric nurses; 60 filled it out again after 15 days. The structural validity and internal consistency of the scale were also studied. Exploratory and confirmatory factor analyses were also conducted. RESULTS: A total of 69 (54.8%) of the participants were male and the majority (72.2%) were <40 years old. The exploratory factor analysis revealed a four factor scale: Leadership, Working environment, Motivating factors and Team spirit (Cronbach alpha: 0.71-0.88). These factors were not identical to the factors of the Finnish version of the scale. The four-factor model created marginally fits the data and exhibits far better indices. Pearson correlation and intraclass correlation coefficient were near to 1, indicating the scale's high reliability. CONCLUSIONS: The scale's properties were very satisfactory indicating that the scale is a reliable measure of job satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: The Greek version of the Kuopio University Hospital Job Satisfaction Scale can be recommended to measure nurses' job satisfaction in Cyprus and Greece. PMID- 27550237 TI - Synthesis of Vertically Standing MoS2 Triangles on SiC. AB - Layered material MoS2 has been attracting much attention due to its excellent electronical properties and catalytic property. Here we report the synthesis of vertically standing MoS2 triangles on silicon carbon(SiC), through a rapid sulfidation process. Such edge-terminated films are metastable structures of MoS2, which may find applications in FinFETs and catalytic reactions. We have confirmed the catalytic property in a hydrogen evolution reaction(HER). The Tafel slope is about 54mV/decade. PMID- 27550238 TI - Successful treatment with afatinib after gefitinib- and erlotinib-induced hepatotoxicity. AB - Clinical trials of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have shown that some patients receiving these agents develop severe hepatotoxicity that necessitates treatment cessation. Both drugs undergo extensive hepatic metabolism mediated predominantly by cytochrome P450 family enzymes. Afatinib is a second-generation, irreversible EGFR-TKI that competes with ATP for binding to EGFR and the related proteins HER2 and HER4 and whose major circulating metabolites are covalent drug-protein adducts. We here describe a patient with EGFR mutation-positive lung adenocarcinoma who developed severe hepatotoxicity during treatment first with gefitinib and then with erlotinib, but who was subsequently able to continue treatment with afatinib for at least 44 weeks with no evidence of hepatotoxicity or disease progression. As far as we are aware, this is the first report of successful treatment with afatinib after the development of high-grade hepatotoxicity during both gefitinib and erlotinib therapy. PMID- 27550239 TI - Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data. AB - BACKGROUND: In the UK, the standard of care for patients with multiple myeloma who received >=2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator). METHODS: Since an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan-Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted. RESULTS: For both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences. CONCLUSIONS: To our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma. PMID- 27550240 TI - Cost-Effectiveness of Non-Invasive and Non-Pharmacological Interventions for Low Back Pain: a Systematic Literature Review. AB - BACKGROUND: Low back pain (LBP) is a major health problem, having a substantial effect on peoples' quality of life and placing a significant economic burden on healthcare systems and, more broadly, societies. Many interventions to alleviate LBP are available but their cost effectiveness is unclear. OBJECTIVES: To identify, document and appraise studies reporting on the cost effectiveness of non-invasive and non-pharmacological treatment options for LBP. METHODS: Relevant studies were identified through systematic searches in bibliographic databases (EMBASE, MEDLINE, PsycINFO, Cochrane Library, CINAHL and the National Health Service Economic Evaluation Database), 'similar article' searches and reference list scanning. Study selection was carried out by three assessors, independently. Study quality was assessed using the Consensus on Health Economic Criteria checklist. Data were extracted using customized extraction forms. RESULTS: Thirty three studies were identified. Study interventions were categorised as: (1) combined physical exercise and psychological therapy, (2) physical exercise therapy only, (3) information and education, and (4) manual therapy. Interventions assessed within each category varied in terms of their components and delivery. In general, combined physical and psychological treatments, information and education interventions, and manual therapies appeared to be cost effective when compared with the study-specific comparators. There is inconsistent evidence around the cost effectiveness of physical exercise programmes as a whole, with yoga, but not group exercise, being cost effective. CONCLUSIONS: The identified evidence suggests that combined physical and psychological treatments, medical yoga, information and education programmes, spinal manipulation and acupuncture are likely to be cost-effective options for LBP. PMID- 27550241 TI - Have Nanoscience and Nanotechnology Delivered? PMID- 27550243 TI - Antibiotic stewardship for drug resistant tuberculosis. PMID- 27550244 TI - Epidemiology of Flexor Tendon Injuries of the Hand in a Northern Finnish Population. AB - BACKGROUND: Flexor tendon injuries cause significant morbidity in working-age population. The epidemiology of these injuries in adult population is not well known. The aim of this study was to describe the epidemiology of flexor tendon injuries in a Northern Finnish population. MATERIAL AND METHODS: Data on flexor tendon injuries, from 2004 to 2010, were retrieved from patient records from four hospitals, which offer surgical repair of the flexor tendon injuries in a well defined area in Northern Finland. The incidence of flexor tendon injury as well as the gender-specific incidence rates was calculated. Mechanism of injury, concomitant nerve injuries, and re-operations were also recorded. RESULTS: The incidence rate of flexor tendon injury was 7.0/100,000 person-years. The incidence was higher in men and inversely related to age. The most common finger to be affected was the fifth digit. In 37% of injuries also digital nerve was affected. The most common finger to have simultaneous digital nerve injury was the thumb. CONCLUSION: Flexor tendon laceration is a relatively rare injury. It predominantly affects working-aged young males and frequently includes a nerve injury, which requires microsurgical skills from the surgeon performing the repair. This study describes epidemiology of flexor tendon injuries and therefore helps planning the surgical and rehabilitation services needed to address this entity. PMID- 27550245 TI - Surgical Management of Fistula-in-ano Among Patients With Crohn's Disease: Analysis of Outcomes After Fistulotomy or Seton Placement-Single-Center Experience. AB - BACKGROUND AND AIM: Fistula-in-ano is a common problem among patients with Crohn's disease and carries significant morbidity. We aimed to study the outcomes of surgical treatment of fistula-in-ano after fistulotomy or seton placement in patients with perianal fistulizing Crohn's disease. MATERIAL AND METHODS: A retrospective observational study of 59 patients diagnosed with Crohn's disease, who were treated surgically for fistula-in-ano between 2010 and 2014 in our department. The assessment of disease complexity included a detailed physical examination, magnetic resonance imaging of the rectum, and examination under anesthesia. Outcomes for analysis included wound healing rate and postoperative incontinence. RESULTS: High transsphincteric fistula was found in 44% of the patients, while mid or low transsphincteric fistulas were found in 51%. Three women (5%) had a rectovaginal fistula. All patients with high transsphincteric fistulas were treated with loose seton placement. Patients with mid- or low-level transsphincteric fistula were offered either fistulotomy or seton placement based on the clinical evaluation. The mean follow-up duration was 1.6 +/- 1.1 years. In terms of recurrence, one patient treated with seton placement presented with recurrence 6 months after seton removal and one patient with fistulotomy failed to achieve wound healing. Minor incontinence was found in six patients treated with fistulotomy and in three patients treated with seton placement; however, this difference was not significant (chi-square = 1.723, df = 1, Monte-Carlo: p = 0.273). CONCLUSION: Fistulotomy could achieve good results in terms of wound healing and incontinence in strictly selected patients with Crohn's disease suffering from low-lying transsphincteric fistulae. For more high-lying or complicated fistulae, seton placement is more appropriate. For high transsphincteric fistulae, the only option is placement of loose seton. PMID- 27550292 TI - Slow versus rapid maxillary expansion in bilateral cleft lip and palate: a CBCT randomized clinical trial. AB - OBJECTIVES: The purpose of this "two-arm parallel" trial was to compare the orthopedic, dental, and alveolar bone plate changes of slow (SME) and rapid (RME) maxillary expansions in patients with complete bilateral cleft lip and palate (BCLP). MATERIAL AND METHODS: Forty-six patients with BCLP and maxillary arch constriction in the late mixed dentition were randomly and equally allocated into two groups. Computer-generated randomization was used. Allocation was concealed with sequentially, numbered, sealed, opaque envelopes. The SME and RME groups comprised patients treated with quad-helix and Haas/Hyrax-type expanders, respectively. Cone-beam computed tomography (CBCT) exams were performed before expansion and 4 to 6 months post-expansion. Nasal cavity width, maxillary width, alveolar crest width, arch width, palatal cleft width, inclination of posterior teeth, alveolar crest level, and buccal and lingual bone plate thickness were assessed. Blinding was applicable for outcome assessment only. Interphase and intergroup comparisons were performed using paired t tests and t tests, respectively (p < 0.05). RESULTS: SME and RME similarly promoted significant increase in all the maxillary transverse dimensions at molar and premolar regions with a decreasing expanding effect from the dental arch to the nasal cavity. Palatal cleft width had a significant increase in both groups. Significant buccal inclination of posterior teeth was only observed for RME. Additionally, both expansion procedures promoted a slight reduction of the alveolar crest level and the buccal bone plate thickness. CONCLUSIONS: No difference was found between the orthopedic, dental, and alveolar bone plate changes of SME and RME in children with BCLP. Both appliances produced significant skeletal transverse gains with negligible periodontal bone changes. Treatment time for SME, however, was longer than the observed for RME. CLINICAL RELEVANCE: SME and RME can be similarly indicated to correct maxillary arch constriction in patients with BCLP in the mixed dentition. PMID- 27550293 TI - Knowledge, opinions and practices of French general practitioners in the assessment of caries risk: results of a national survey. AB - OBJECTIVES: The objective of this study was to describe the knowledge, opinions and practices of French general dental practitioners with respect to caries risk assessment (CRA) through the use of a national questionnaire survey. MATERIALS AND METHODS: A postal questionnaire survey was applied to a simple random sample of dentists (n = 2000) in France. Descriptive and logistic regression analyses were performed. RESULTS: The response rate was 34.7 %. Of the respondents, 38.4 % reported that CRA was not part of their routine practice. Among those who claimed to use CRA only 4.5 % did so using a specific evaluation form. Responses showed that there is great variation among respondents with respect to the importance given to different factors to be considered for the development of a treatment plan in adults. Moreover, 32.3 % of respondents reported no regular scheduling of preventive care based on the caries risk of their patients. Nearly 12 % of respondents admitted they did not know exactly what minimal intervention in caries management involved. The results also showed that socio-demographic characteristics of the practitioner influence the use of CRA and other practice patterns. CONCLUSIONS: CRA has not widely entered clinical practice in France. CLINICAL RELEVANCE: This study, the first of its nature in France, shows the need to develop the use of CRA in daily dental practice in France. PMID- 27550294 TI - Impact of a 2-Week Oncology Placement on Medical Students' Perception of Cancer. AB - Statistics show that more than one in two people born after 1960 in the UK will develop cancer during their lifetime. However, a 2013 study found that only 36 % of UK medical schools offer dedicated clinical teaching in oncology. The aim of this study was to assess the views of medical students on five domains of oncology before and after their first clinical placement, to assess the impact, and to obtain students' views on the oncology curriculum. A 28-item questionnaire was developed to compare responses before and after the students' first 2-week clinical placement, and impact was measured as a positive or negative deviation from a baseline response. Students were asked about their career intentions and to evaluate their received teaching. Thirty-six (80 %) students responded to the questionnaire. The largest areas of change were identified in students' confidence in breaking bad news, recognising red flag symptoms, and awareness of the complications of cancer management. Following their placement, 19 students said they would consider a career in oncology, 14 said they would not, and 2 were undecided. Students stated that Maggie's Centre, a patient support facility, was the most useful learning experience. The evidence demonstrates that all students should experience oncology in a variety of settings to aid their learning. Student feedback and perception can help to guide and shape medical teaching. PMID- 27550295 TI - The successful use of tocilizumab as third-line biologic therapy in a case of refractory anti-synthetase syndrome. PMID- 27550297 TI - Interleukin 26 suppresses receptor activator of nuclear factor kappaB ligand induced osteoclastogenesis via down-regulation of nuclear factor of activated T cells, cytoplasmic 1 and nuclear factor kappaB activity. AB - OBJECTIVE: IL-26 has been shown to have high expression in RA. However, the effects of IL-26 on bone destruction in RA have not been evaluated. The aim of this study was to investigate the effects and mechanisms of IL-26 on RANK ligand (RANKL)-induced osteoclastogenesis. METHODS: We treated cells with IL-26 in RANKL induced oseteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay and F-actin ring formation. The mechanism of the inhibition was studied by biochemical analyses such as RT-PCR, immunofluorescence staining and immunoblotting. In addition, cell viability was determined by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: IL-26 inhibited RANKL-induced TRAP-positive multinucleated cells and inhibited RANKL induced nuclear factor kappaB (NF-kappaB) activation and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, IL-26 significantly inhibited the bone-resorbing activity and F actin ring formation ability of mature osteoclasts. Moreover, IL-26 suppressed RANKL-induced mitogen-activated protein kinase activation and NFATc1 downstream gene expression. CONCLUSION: We suggest that the inhibitory activity of IL-26 on osteoclastogenesis is via down-regulation of RANKL-induced NF-kappaB and NFATc1 expression. Our results suggest IL-26 as a possible new remedy against osteolytic bone destruction. PMID- 27550296 TI - Transforming growth factor beta activated kinase 1: a potential therapeutic target for rheumatic diseases. AB - Pro-inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha are central regulators of autoinflammatory diseases. While targeting these cytokines has proven to be a successful clinical strategy, the long-term challenges such as drug resistance, lack of efficacy and poor clinical outcomes in some patients are some of the limitations faced by these therapies. This has ignited strategies to reduce inflammation by potentially targeting a variety of molecules, including cell surface receptors, signalling proteins and/or transcription factors to minimize cytokine-induced inflammation and tissue injury. In this regard, transforming growth factor beta activated kinase 1 (TAK1) is activated in the inflammatory signal transduction pathways in response to IL-1beta, TNF-alpha or toll-like receptor stimulation. Because of its ideal position upstream of mitogen activated protein kinases and the IkappaB kinase complex in signalling cascades, targeting TAK1 may be an attractive strategy for treating diseases characterized by chronic inflammation. Here, we discuss the emerging role of TAK1 in mediating the IL-1beta, TNF-alpha and toll-like receptor mediated inflammatory responses in diseases such as RA, OA, gout and SS. We also review evidence suggesting that TAK1 inhibition may have potential therapeutic value. Finally, we focus on the current status of the development of TAK1 inhibitors and suggest further opportunities for testing TAK1 inhibitors in rheumatic diseases. PMID- 27550298 TI - Millet-seed conjunctival nodules. PMID- 27550299 TI - An easy prediction rule for diffuse cutaneous systemic sclerosis using only the timing and type of first symptoms and auto-antibodies: derivation and validation. AB - OBJECTIVE: DcSSc is associated with high morbidity related to widespread skin disease and poor prognosis due to earlier and more severe organ involvement. The objective of this study is to derive and validate a simple prediction rule for identifying patients at the time of initial diagnosis of SSc who are likely to progress to dcSSc. METHODS: The Nijmegen cohort consists of 619 SSc patients. Logistic regression was used for predictive modelling. A prediction rule was created by rounding regression coefficients. Patients were stratified as being at low risk (<1) or high risk (?1) of progression to dcSSc. Performance was analysed in 445 SSc patients from Madrid. RESULTS: One hundred and seventy-four out of 535 patients were classified as dcSSc. The final model consisted of gender, time between RP and non-RP, sclerodactyly (first non-Raynaud symptom) and SSc-specific auto-antibodies. The model performed well in the derivation cohort [area under the curve = 0.78 (95% CI: 0.74, 0.82)] and validation cohort [area under the curve = 0.78 (95% CI: 0.74, 0.83)]. At the optimal cut point (1) for the prediction rule, sensitivity was 87% and specificity 61% in the derivation cohort, compared with 78% and 65% in the validation cohort. Upon application of the prediction rule to 392 lcSSc patients at initial diagnosis, 32 out of 34 patients were correctly classified as dcSSc. CONCLUSION: A simple prediction rule was designed to attribute a low/high risk category for development of dcSSc.This method is suited for assigning intensified screening at the time of initial diagnosis of SSc to patients most at risk for dcSSc. It provides the opportunity for early identification of potential dcSSc patients for enrolment into clinical trials. PMID- 27550300 TI - Comment on: Rituximab in autoimmune connective tissue disease-associated interstitial lung disease: reply. PMID- 27550301 TI - Monotherapy with biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis. AB - Current EULAR guidelines state that biologic DMARD (bDMARD) therapy should be administered in combination with MTX or other conventional synthetic (cs) DMARD in RA. Nonetheless, a third of patients for whom a bDMARD agent is prescribed take it in the absence of concurrent csDMARD therapy. While the reasons underlying the low uptake of bDMARD-csDMARD combination therapy in clinical practice have not been well delineated, they may include poor adherence, contraindication to csDMARD therapy and adverse effects, as well as csDMARD withdrawal following remission. The challenges surrounding bDMARD therapy and the benefit/risk ratio of biologic monotherapy when compared with combination with a csDMARD will be discussed. We will provide insights into these important issues, as well as reviewing the evidence base differentiating biologic agents and exploring therapeutic options for patients with rheumatoid arthritis for whom csDMARD therapy is contraindicated or discontinued. PMID- 27550302 TI - Kidney disease in primary anti-phospholipid antibody syndrome. AB - APS is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for aPL. APS can be isolated (primary APS) or associated with other autoimmune diseases. The kidney is a major target organ in APS, and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal vasculature and renal veins). Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal involvement in patients with definite APS is treated with long-term anticoagulants as warfarin, but new treatments are being tried. The aim of this article is to review the links between primary APS and kidney disease. PMID- 27550303 TI - Comment on: rituximab in autoimmune connective tissue disease-associated interstitial lung disease. PMID- 27550304 TI - The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis. AB - OBJECTIVE: To explore the influence of TNF inhibitor (TNFi) therapy and rituximab (RTX) upon the incidence of cancer in patients with RA and prior malignancy. METHODS: The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi cohort, RTX cohort and synthetic DMARDs (sDMARD) cohort. RESULTS: We identified 425 patients with a prior malignancy from 18 000 RA patients in the study. Of these, 101 patients developed a new malignancy. The rates of incident malignancy were 33.3 events/1000 person-years (py) in the TNFi cohort, 24.7 events/1000 py in the RTX cohort and 53.8 events/1000 py in the sDMARD cohort. The age- and gender-adjusted hazard ratio was 0.55 (95% CI: 0.35, 0.86) for the TNFi cohort and 0.43 (95% CI: 0.10, 1.80) for the RTX cohort in comparison with the sDMARDs cohort. The 17.0% of patients in the sDMARDs cohort had a recurrence of the same cancer in comparison with the 12.8% and the 4.3% in the TNFi and RTX cohorts, respectively. CONCLUSIONS: Although numbers are still low, it seems that patients with RA and prior malignancy selected to receive either a TNFi or RTX in the UK do not have an increased risk of future incident malignancy. PMID- 27550305 TI - Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial. AB - BACKGROUND: Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. METHODS/DESIGN: We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. DISCUSSION: This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. TRIAL REGISTRATION: This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ). PMID- 27550306 TI - Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique. AB - OBJECTIVE: To investigate the associations between Alberta Stroke Program Early CT Score (ASPECTS) or distribution and sidedness of acute infarction and clinical outcomes following intervention with a direct aspiration first pass technique (ADAPT). METHODS: A review was performed of patients who had undergone thrombectomy with ADAPT for emergent large vessel occlusions of the middle cerebral artery (MCA) between December 2012 and May 2015. Preintervention CT scans were reviewed by a blinded radiologist to calculate ASPECTS and determine the distribution of infarction. Clinical outcomes were compared for subsets of patients depending upon ASPECTS and regional infarction distribution (cortical, subcortical, or both). RESULTS: One hundred and fifty-four patients (50% female, mean age 67) underwent thrombectomy using ADAPT for MCA emergent large vessel occlusion. The median presenting National Institute of Health Stroke Scale score was 15. Fifty-five per cent of patients had left-side occlusions. Similar good outcomes were achieved for patients with perfect and non-perfect ASPECTS (modified Rankin Scale (mRS) 0-2: 63% vs 51%, respectively; p=0.20). Similar outcomes were also achieved for patients with 'poor' ASPECTS (<=6) compared with those with ASPECTS >6 (mRS 0-2: 52% vs 53%, respectively; p=0.91). Regional distribution and sidedness of core infarction on preintervention CT also did not correlate with worse outcomes. CONCLUSIONS: Patients with moderate-sized core infarcts involving various distributions in either hemisphere can potentially achieve similar good outcomes compared with those with no core infarction at presentation. A treatment algorithm for acute ischemic stroke, which employs hardline ASPECTS thresholds or excludes patients with basal ganglia infarcts, might preclude patients who would potentially benefit from mechanical thrombectomy with ADAPT. PMID- 27550307 TI - Ultra-small Tetrametallic Pt-Pd-Rh-Ag Nanoframes with Tunable Behavior for Direct Formic Acid/Methanol Oxidation. AB - Reversible tuning of ultra-small multimetallic Pt-Pd-Rh-Ag nanoframes is achieved. These nanoframes showed tunable and reversible modes for the oxidation of small organic molecules by simply inducing segregation with adsorbates, such as SO42- and OH- . This is the first example of reversible segregation under electrocatalytic conditions in atomic-sized electrocatalysts. These nanoframes also showed a controllable activity and good stability for the oxidation of small organic molecules. PMID- 27550308 TI - With regard to the paper by Zannad et al. entitled Assessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment versus risk aversion. PMID- 27550310 TI - Perfusion computed tomography: 4 cm versus 8 cm coverage size in subjects with chronic carotid artery stenosis. AB - OBJECTIVE: The impact of coverage size on global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) parameters has not been investigated in patients with chronic carotid artery stenosis. METHODS: 63 patients with stenosis of >70% within a single internal carotid artery and neurological symptoms were randomly assigned to two well matched groups. Differences in CT perfusion scan over a 4 cm or 8 cm range of the brain were compared between the two groups. RESULTS: The CBF and CBV values were higher in the 4 cm coverage size than in the 8 cm coverage size (by 14.7 and 10.7% on the ipsilateral side and 17.2 and 7.8% on the contralateral side, respectively; all p < 0.001). The MTT value was higher in the 4 cm coverage size than in the 8 cm coverage size on the ipsilateral side (9.6%; p < 0.001). There was no difference between MTT values in the contralateral size. There were no differences between TTP values on the ipsilateral and contralateral sides. The relative indices rMTT and rTTP were higher in the 4 cm coverage size than in the 8 cm coverage size (8.2%, p < 0.001, and 1.1%, p < 0.005, respectively). CONCLUSION: Absolute CBF and CBV values and relative rMTT and rTTP indices in patients with low CBF and low CBV are highly dependent on coverage size. We recommend using a 4 cm coverage size to assess global cerebral perfusion parameters owing to better accuracy and quicker post-processing. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first article to compare the influence of 4 cm vs 8 cm coverage size on cerebral perfusion parameters such as CBF, CBV, MTT and TTP in subjects with chronic carotid artery stenosis. PMID- 27550309 TI - The cytochrome b Zn binding amino acid residue histidine 291 is essential for ubihydroquinone oxidation at the Qo site of bacterial cytochrome bc1. AB - The ubiquinol:cytochrome (cyt) c oxidoreductase (or cyt bc1) is an important membrane protein complex in photosynthetic and respiratory energy transduction. In bacteria such as Rhodobacter capsulatus it is constituted of three subunits: the iron-sulfur protein, cyt b and cyt c1, which form two catalytic domains, the Qo (hydroquinone (QH2) oxidation) and Qi (quinone (Q) reduction) sites. At the Qo site, the pathways of bifurcated electron transfers emanating from QH2 oxidation are known, but the associated proton release routes are not well defined. In energy transducing complexes, Zn2+ binding amino acid residues often correlate with proton uptake or release pathways. Earlier, using combined EXAFS and structural studies, we identified Zn coordinating residues of mitochondrial and bacterial cyt bc1. In this work, using the genetically tractable bacterial cyt bc1, we substituted each of the proposed Zn binding residues with non protonatable side chains. Among these mutants, only the His291Leu substitution destroyed almost completely the Qo site catalysis without perturbing significantly the redox properties of the cofactors or the assembly of the complex. In this mutant, which is unable to support photosynthetic growth, the bifurcated electron transfer reactions that result from QH2 oxidation at the Qo site, as well as the associated proton(s) release, were dramatically impaired. Based on these findings, on the putative role of His291 in liganding Zn, and on its solvent exposed and highly conserved position, we propose that His291 of cyt b is critical for proton release associated to QH2 oxidation at the Qo site of cyt bc1. PMID- 27550311 TI - Marinibaculum pumilum gen. nov., sp. nov., isolated from seawater. AB - A Gram-stain-negative, facultatively anaerobic, motile and rod-shaped strain, designed H2T, was isolated from the Western Pacific Ocean, and subjected to a taxonomic investigation using a polyphasic approach. Strain H2T grew at 15-40 degrees C and pH 6.0-9.0 (optimum 37 degrees C and pH 6.5), and with 1-10 % (w/v) NaCl (optimum 2 %). The predominant respiratory quinone was ubiquinone-10 (Q-10) and the major fatty acids identified were C19 : 0 cyclo omega8c, C18 : 1omega7c, C18 : 0 and 11-methyl-C18 : 1omega7c. The polar lipids of strain H2T consisted of phosphatidylglycerol, one unknown phospholipid, one unknown glycolipid and three unidentified aminolipids. The DNA G+C content was 75.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain H2T formed a distinct clade belong to the family Rhodospirillaceae within the Alphaproteobacteria. On the basis of morphological, physiological and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain H2T represents a novel species in a new genus in the family Rhodospirillaceae, for which the name Marinibaculumpumilum gen. nov., sp. nov. is proposed. The type strain of the type species is H2T(=MCCC 1K02279T=KCTC 42964T). PMID- 27550313 TI - Can hibernators sense and evade fires? Olfactory acuity and locomotor performance during deep torpor. AB - Increased habitat fragmentation, global warming and other human activities have caused a rise in the frequency of wildfires worldwide. To reduce the risks of uncontrollable fires, prescribed burns are generally conducted during the colder months of the year, a time when in many mammals torpor is expressed regularly. Torpor is crucial for energy conservation, but the low body temperatures (T b) are associated with a decreased responsiveness and torpid animals might therefore face an increased mortality risk during fires. We tested whether hibernators in deep torpor (a) can respond to the smell of smoke and (b) can climb to avoid fires at T bs below normothermic levels. Our data show that torpid eastern pygmy possums (Cercartetus nanus) are able to detect smoke and also can climb. All males aroused from torpor when the smoke stimulus was presented at an ambient temperature (T a) of 15 degrees C (T b ~18 degrees C), whereas females only raised their heads. The responses were less pronounced at T a 10 degrees C. The first coordinated movement of possums along a branch was observed at a mean T b of 15.6 degrees C, and animals were even able to climb their prehensile tail when they reached a mean T b of 24.4 degrees C. Our study shows that hibernators can sense smoke and move at low T b. However, our data also illustrate that at T b <=13 degrees C, C. nanus show decreased responsiveness and locomotor performance and highlight that prescribed burns during winter should be avoided on very cold days to allow torpid animals enough time to respond. PMID- 27550312 TI - HIV-1 Vpr reactivates latent HIV-1 provirus by inducing depletion of class I HDACs on chromatin. AB - HIV-1 Vpr is an accessory protein that induces proteasomal degradation of multiple proteins. We recently showed that Vpr targets class I HDACs on chromatin for proteasomal degradation. Here we show that Vpr induces degradation of HDAC1 and HDAC3 in HIV-1 latently infected J-Lat cells. Degradation of HDAC1 and HDAC3 was also observed on the HIV-1 LTR and as a result, markers of active transcription were recruited to the viral promoter and induced viral activation. Knockdown of HDAC1 and HDAC3 activated the latent HIV-1 provirus and complementation with HDAC3 inhibited Vpr-induced HIV-1 reactivation. Viral reactivation and degradation of HDAC1 and HDAC3 was conserved among Vpr proteins of HV-1 group M. Serum Vpr isolated from patients or the release of virion incorporated Vpr from viral lysates also activated HIV-1 in latently infected cell lines and PBMCs from HIV-1 infected patients. Our results indicate that Vpr counteracts HIV-1 latency by inducing proteasomal degradation of HDAC1 and 3 leading to reactivation of the viral promoter. PMID- 27550315 TI - Variation in the Presence of Simple Home Modifications of Older Americans: Findings from the National Health and Aging Trends Study. AB - OBJECTIVES: To investigate the association between sociodemographic and economic factors and the presence of simple home modifications (HMs) among older adults in the United States. DESIGN: Cross-sectional. SETTING: National Health and Aging Trends Study (2011, Round 1). PARTICIPANTS: Community-dwelling Medicare enrollees aged 65 and older (N = 6,628). MEASUREMENTS: The primary dependent variable was the reported presence or absence of simple HMs (grab bars in the shower or near the toilet, shower seats, raised toilet seats). RESULTS: Of the individuals sampled, 60.7% reported having at least one HM of interest. Black (odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.68-0.91) and Hispanic (OR = 0.60, 95% CI = 0.45-0.78) respondents were less likely than white, non-Hispanic respondents to have HMs. Those with more education (high school graduate: OR = 1.20, 95% CI = 1.01-1.42; >high school: OR = 1.36, 95% CI = 1.14-1.62) and larger social networks (>=4 people; OR = 1.46, 95% CI = 1.12-1.89) were more likely to have at least one HM, whereas being divorced (OR = 0.57, 95% CI = 0.43-0.74) was associated with lower likelihood. Income (OR = 1.01, 95% CI = 0.97-1.05), Medicaid enrollment (OR = 0.98, 95% CI = 0.77-1.25), and living alone (OR = 1.02, 95% CI = 0.85-1.23) were not significantly associated with the presence of HMs. CONCLUSION: Minorities, individuals with less education, and those with less social support are less likely to have HMs. Awareness of these disparities and the shortcomings of the HM delivery system is important to clinicians and policy makers who seek to prevent falls and facilitate aging in place for all older Americans. PMID- 27550314 TI - Ethanolic extract of Schizonepeta tenuifolia attenuates osteoclast formation and activation in vitro and protects against lipopolysaccharide-induced bone loss in vivo. AB - BACKGROUND: Excessive osteoclast activity is a major cause of metabolic bone disorders, such as osteopenia, rheumatoid arthritis, and osteoporosis. Thus, discovery of agents targeting osteoclast differentiation and bone resorption is important for development of novel treatments for bone diseases. It has been demonstrated that ethanolic extract of schizonepeta tenuifolia (EEST) has potent anti-oxidant and anti-inflammatory activities. However, the beneficial effects of EEST on bone metabolism have not been studied. Therefore, we intend to investigate the effects of EEST on osteoclast differentiation. METHODS: We examined the effects and mechanisms of action of the EEST on osteoclastogenesis in vitro in bone marrow macrophages (BMMs) stimulated with receptor activator of nuclear factor kappa-B ligand (RANKL) and in vivo using a mouse model of lipopolysaccharide (LPS)-induced bone destruction. RESULTS: We found that EEST inhibited phosphorylation of Akt and IkB at early stages of RANKL-induced osteoclastogenesis. Furthermore, EEST negatively controlled the transcription and translation levels of nuclear factor of activated T cells c1 (NFATc1) and the translation level of c-Fos at the final stage of osteoclast differentiation. Reflecting these effects, EEST blocked both filamentous actin (F-actin) ring formation and bone resorbing activity of mature osteoclasts in vitro. The inhibitory effects of EEST on osteoclast formation and activity were observed in an LPS-mediated bone erosion mouse model using micro-CT and histological analysis. CONCLUSIONS: EEST is a potential agent that is able to treat osteoclast related bone diseases, such as osteoporosis. PMID- 27550316 TI - Self-organized sorting limits behavioral variability in swarms. AB - Swarming is a phenomenon where collective motion arises from simple local interactions between typically identical individuals. Here, we investigate the effects of variability in behavior among the agents in finite swarms with both alignment and cohesive interactions. We show that swarming is abolished above a critical fraction of non-aligners who do not participate in alignment. In certain regimes, however, swarms above the critical threshold can dynamically reorganize and sort out excess non-aligners to maintain the average fraction close to the critical value. This persists even in swarms with a distribution of alignment interactions, suggesting a simple, robust and efficient mechanism that allows heterogeneously mixed populations to naturally regulate their composition and remain in a collective swarming state or even differentiate among behavioral phenotypes. We show that, for evolving swarms, this self-organized sorting behavior can couple to the evolutionary dynamics leading to new evolutionarily stable equilibrium populations set by the physical swarm parameters. PMID- 27550318 TI - New suturing technique for robotic-assisted vaginal cuff closure during single site hysterectomy. AB - To describe a simple and efficient technique for suturing the vaginal cuff in robotic-assisted single-site hysterectomy using barbed suture and a straight needle. Consecutive patients undergoing robotic-assisted single-site hysterectomy from February 2014 to August 2015 at Dong San Hospital, Keimyung University were included. Surgeons used two barbed sutures in a running fashion to close the vaginal cuff. A barbed suture was exclusively used with a straightened needle in upward direction from posterior vaginal cuff to anterior vaginal cuff which played a pivotal role for closure. A total of 100 patients underwent robotic assisted single-site hysterectomy. The total operation time was 132.5 min and vaginal cuff closure time was 12.0 min. There were no postoperative complications; vaginal cuff dehiscence, vaginal cuff infection, and vaginal bleeding that require surgical intervention or admission. The use of barbed suture with straightened needle to close the vaginal cuff in robotic-assisted single-site hysterectomy is easy to perform and demonstrates safety and efficacy. This technique offers secure, fast, and effective incision closure. PMID- 27550319 TI - Para-Nonylphenol Induces Apoptosis of U937 Human Monocyte Leukemia Cells in vitro. AB - BACKGROUND: Human autoimmune diseases are caused by a variety of factors, such as environmental chemicals, including para-nonylphenol. Macrophages play many critical roles in the regulation of immunity and the progression of autoimmune diseases. However, little information is available regarding the effects of para nonylphenol on cellular signaling pathways and the death of these cells in vitro. Here, we show that very high concentrations of para-nonylphenol (50-100 MUM) induce apoptosis in U937 human monocyte leukemia cells in a dose-dependent manner. METHODS: Cell viability was judged using the trypan blue exclusion method. FACS analysis for DNA fragmentation was conducted, cellular signaling pathways were evaluated using western blot analysis, and caspase activity was measured by using substrates. U937 cells were differentiated by PMA. RESULTS: Treatment with > 50 MUM para-nonylphenol induced apoptosis in U937 monocyte cells and MCF- 7 and MDA-MB231 human breast cancer cells. We found cytochrome c release from the mitochondria to the cytoplasm, DNA fragmentation, and decreased expression of anti-apoptotic protein Bcl-XL. Caspase 3 and 9 were induced, but caspase 1 and 3-inhibitor treatment suppressed apoptosis. Para-nonylphenol decreased the levels of activated AKT and increased the levels of activated JNK/SAPK at 15 min after treatment. Furthermore, with PMA treatment, U937 cells were differentiated into a macrophage-like phenotype and showed attenuated cell death against para-nonylphenol. CONCLUSION: As this assay system is simple and rapid, it may represent a useful artificial tool to clarify the signaling pathways of apoptotic cell death in human monocytes in vitro. PMID- 27550320 TI - Which ecological determinants influence Australian children's fruit and vegetable consumption? AB - This study investigated determinants of fruit and vegetable (F&V) consumption among regional and remote Western Australian (WA) children, using an Ecological Model of Health Behaviour. Semi-structured interviews were conducted with 20 key informants (Health Workers, Food Supply Workers, and School/Youth Workers) purposively sampled from across regional and remote WA. Interviews were transcribed, analysed thematically using QSR-NVivo 10 software, and embedded within an Ecological Model of Health Behaviour to demonstrate the multiple levels of influence on health. Key determinants of F&V consumption at the intrapersonal level included attitude and food literacy among children. Key interpersonal level determinants included role modelling and parental food literacy. Institutional determinants included health service provision, school nutrition education and food skill programs. F&V availability, community networks and health-promoting spaces were key themes affecting families at the community level. The public policy level influencer included implementation of a store policy within local food outlets. Study findings suggested participatory programs with an emphasis on parental involvement and role modelling could increase F&V intake among children living in regional and remote areas; while school curriculum linkages were essential for school-based programs. Policy makers should consider further investment in school food literacy programs and family programs that are delivered collaboratively. Further, support of local food supply options and support for healthy food policies in food outlets are critical next steps. This study contributes new knowledge to build the evidence base and facilitate the development of targeted strategies to increase consumption of F&V among children living in regional and remote areas. PMID- 27550321 TI - Cultural challenges when developing anti-tobacco messages for Indigenous Australians. AB - Recently, many programs have been funded to tackle Indigenous Australian smoking. This study assessed what challenges and unexpected responses could occur when developing anti-tobacco messages for Indigenous communities. A cross-sectional telephone survey of organizations involved in making anti-tobacco messages for the target population was conducted in 2012-2013. Open-ended questions explored cultural challenges to message development and unexpected outcomes. Responses were noted and these qualitative data were independently coded by two researchers using an inductive analysis. Non-parametric tests explored associations between organization orientation, whether target group feedback about messages was sought (pre-tests) and the presence of the above factors. The 47 organizations represented included: 22 Aboriginal Medical Services (AMS), 13 government organizations (GO), eight non-government organizations (NGO) and four universities. The response rate was 83%. Cultural challenges were reported equally by organizations oriented towards Aboriginal communities and those oriented towards the general population. Organizations conducting target group pre-tests of the messages were more likely to report cultural challenges (p = 0.002). Four main themes were revealed: the diversity of Aboriginal and Torres Strait Islander cultures; the selection of role models; conflicts and delays; and unexpected outcomes. Nearly 60% of organizations reported better-than-expected outcomes e.g. community appreciation and pride. A further 40% reported negative responses, e.g. messages being misunderstood or confronting. Cultural challenges and unexpected outcomes are reported by Australian organizations when developing anti-tobacco messages for Indigenous Australians warranting attention to improve the salience of anti-tobacco messages for Indigenous peoples.NB. In this paper, Indigenous Australians is a term used to refer to Aboriginal and Torres Strait Islander peoples, the first inhabitants of Australia. No offence is intended. The authors acknowledge and respect that Aboriginal and Torres Strait Islander people are diverse populations with different language and cultural groups. PMID- 27550322 TI - A ratiometric fluorescent sensor for the mitochondrial copper pool. AB - Copper plays a key role in the modulation of cellular function, defence, and growth. Here we present InCCu1, a ratiometric fluorescent sensor for mitochondrial copper, which changes from red to blue emission in the presence of Cu(i). Employing this probe in microscopy and flow cytometry, we show that cisplatin-treated cells have an impaired ability to accumulate copper in the mitochondria. PMID- 27550323 TI - Toward RNA Repair of Diamond Blackfan Anemia Hematopoietic Stem Cells. AB - Diamond blackfan anemia (DBA) is a well-known inherited bone marrow failure syndrome mostly caused by mutations in ribosomal protein (RP) genes but also rarely in the hematopoietic transcription factor gene, GATA1, or TSR2, a ribosomal protein (Rps26) chaperone gene. About 25% of patients have heterozygous mutations in the RPS19 gene, which leads to haploinsufficiency of Rps19 protein in most cases. However, some RPS19 missense mutations appear to act in a dominant negative fashion. DBA typically leads to a hypoplastic anemia that becomes apparent during the first year of life, and standard treatment includes steroids or red blood cell transfusions, each modality having attendant side effects. The only curative therapy is allogeneic stem-cell transplantation, but this option is limited to patients with a histocompatible donor. DBA-mutant embryonic, induced pluripotent, and hematopoietic stem cells all exhibit growth abnormalities that can be corrected by DNA gene transfer, suggesting the possibility of ex vivo autologous gene therapy. The authors have been interested in the application of spliceosome-mediated mRNA trans-splicing (SMaRT) technology to RNA repair of DBA stem cells. Compared with gene replacement or other RNA re-programming approaches, SMaRT has several potential advantages. First, delivery of the entire normal cDNA is unnecessary, thus minimizing the overall size of the construct for packaging into a viral delivery vector. Second, RNA transcription of the corrected gene relies on the cell's endogenous transcriptional, processing, and regulatory machinery, thereby ensuring faithful and contextual expression. Third, RNA trans-splicing employs the endogenous spliceosome enzymatic machinery present in nearly all cells. Fourth, RNA trans-splicing converts mutant transcripts into therapeutically useful mRNA, and thus may be capable of treating disorders caused by dominant negative mutations. This review critically assesses prospects for both gene and RNA repair in DBA stem cells. PMID- 27550324 TI - Distal clavicular osteolysis in adults: association with bench pressing intensity. AB - OBJECTIVES: To investigate the association between distal clavicular osteolysis (DCO) and bench pressing intensity. METHODS: From a retrospective review of MRI shoulder reports of individuals between 20 and 40 years of age, 262 male patients with DCO and 227 age-matched male patients without DCO were selected. All patients had completed a bench pressing questionnaire. The patients' bench pressing frequency (times per week), duration (years of bench pressing), bench pressing weight (maximum bench pressing weight with one repetition = 1RM) and the ratio of bench pressing weight to body weight were compared between both groups using Chi-square and Mann-Whitney tests. RESULTS: The results showed that 56 % (146/262) of patients with DCO were high-intensity bench pressers (1RM more than 1.5 times the body weight) compared to 6 % (14/227) in patients without DCO. High intensity bench pressing was a risk factor for DCO (OR = 19; 95 %CI = 11-35; p < 0.001). Low-intensity bench pressing (1RM less than 1.5 times the body weight) was not a risk factor for DCO (OR = 0.6; 95 % CI = 0.4-0.8). High frequency (>1*/week) and duration (>5 years) of bench pressing were risk factors. In bench pressers who suffered from DCO, the mean 1RM was 283 lbs (+/-SD 57) compared to 209 lbs (+/-SD 60) in bench pressers not affected by DCO (p < 0.001, Mann Whitney). CONCLUSIONS: High-intensity, but not low-intensity bench pressing is a risk factor for DCO. PMID- 27550326 TI - Students' educational experiences and interaction with residents on night shifts. AB - BACKGROUND: The purpose of this mixed-methods study was to investigate whether increased night shifts for students on paediatric rotations had any negative impact on their overall quality of educational experiences in light of the implementation of duty-hour restrictions. METHODS: Both quantitative and qualitative data were collected from 30 students on paediatric rotations during the academic year 2011/12. Students completed two questionnaires, one in response to their experiences during the day shifts and another in response to their experiences during the night shifts. Only 25 cases were retained for the final analyses. The non-parametric Wilcoxon signed-rank test was used to analyse the quantitative data, and constant comparative thematic analyses, as described by Creswell, were used to analyse the qualitative data. [Do] increased nights shifts for students ... [have] any negative impact on their overall quality of educational experiences[?] RESULTS: The results indicated that students' perceived quality of experiences during the night shifts was greater, compared with their day shifts. Students reported having more time to socialise during the night shifts. They further reported that informal ways of learning, such as impromptu teaching and spontaneous discussions on clinical problems, were more beneficial, and these often occurred in abundance during the night shifts as opposed to the scheduled didactic teaching sessions that occur during the day shifts. DISCUSSION: This study documented many unanticipated benefits of night shifts. The feeling of cohesiveness of the night team deserves further exploration, as this can be linked to better performance outcomes. More consideration should be given to implementing night shifts as a regular feature of clerkships. PMID- 27550328 TI - Kennel Club to review vet checks for German shepherd dogs. PMID- 27550325 TI - Factors related to non-compliance to HPV vaccination in Roraima-Brazil: a region with a high incidence of cervical cancer. AB - BACKGROUND: To evaluate the HPV vaccination coverage in Boa Vista, Roraima (Brazil) and to identify personal and socioeconomic factors related to non compliance to HPV vaccination. METHODS: A school-based, cross-sectional study was conducted by distributing a self-administered questionnaire to the parents or guardians of pre-adolescent girls. The questionnaire addressed compliance to, knowledge about and perception of HPV and the HPV vaccine. Between July and November 2015, 13 private and public schools were visited based on a random cluster sampling method. RESULTS: A total of 1337 questionnaires were distributed to all female students in the target age group, and 797 were completed and returned (the participation rate was 59.6 %). The vaccination coverage rate was 82.7 % and was higher among public school students than among private school students (84.1 % vs 56.3 %; p = 0.003). Most parents (60 %) incorrectly answered more than half of the questions related to HPV knowledge, and limited knowledge about HPV and the HPV vaccine correlated with lower compliance to vaccination (adjusted OR = 1.42; 95 % CI: 1.01 to 2.76). In the perception analysis, the belief that the HPV vaccine is important for the daughter was an important protective factor (adjusted OR = 0.62; 95 % CI: 0.23 to 0.93), and concern about adverse effects of the HPV vaccine was a risk factor for non-compliance (adjusted OR = 1.66; 95 % CI: 1.01 to 2.71). Family income, religion and education level of the parents or guardians did not correlate with compliance to vaccination. CONCLUSION: HPV vaccination coverage was high in Boa Vista, Brazil, but knowledge about the vaccine was deficient. This deficiency was associated with a distorted perception and was negatively associated with compliance to vaccination. Actions aimed at informing the public about the HPV vaccine, including its risks and benefits, are needed to attain higher vaccination coverage in Brazil. PMID- 27550329 TI - Non-stun slaughter: FSA gives reassurance on data collection. PMID- 27550330 TI - Vets flock to sheep health club events. PMID- 27550332 TI - Improving human health and equality through sustainable livestock. PMID- 27550333 TI - Raising the profession's profile. PMID- 27550331 TI - Research project aims to 'future-proof' sheep and goat farming. PMID- 27550334 TI - Tickborne fever associated with abortion outbreak in dairy cows. AB - Anaplasma phagocytophilum detected in aborting cows on rough grazingLead poisoning in bullocksPersistent bovine viral diarrhoea virus infection and colisepticaemia in a 20-hour-old calfAbortion due to bovine herpesvirus 1 in a four-year-old cowTickborne fever in lambsInfectious sinusitis due to Mycoplasma gallisepticum in pheasants These are among matters discussed in the disease surveillance report for May 2016 from SAC Consulting: Veterinary Services (SAC C VS). PMID- 27550335 TI - Chlamydiaceae: an update on nomenclature. PMID- 27550336 TI - Dearth of evidence for EBVM. PMID- 27550337 TI - Masters in clinical veterinary research. AB - A new masters qualification from the BSAVA aims to encourage and support clinical research in practice. As Frances Barr explains, it is aimed at those looking for a professional challenge. PMID- 27550339 TI - Functional effects of cold stimulation on taste perception in humans. AB - Thermal modulation of signaling pathways leads to excitation of taste receptor cells, but the underlying mechanisms remain unclear. Furthermore, it has long been known that there are contrast effects in various senses. In this study, we investigated cold-taste contrast and the relationship between taste and somatosensation. We lowered intraoral temperature using cold stimulus as a pretreatment, then returned to normal temperature in 249 healthy subjects, before administering room temperature taste-stimulating solutions to investigate changes in sensitivity to the four basic tastes (Sweet, Salt, Sour, and Bitter). Statistical comparisons of taste recognition thresholds before and after cold stimulus showed increased taste sensitivity for all four basic tastes. After categorizing different levels of pre-cold stimulus taste sensitivity into groups and comparing changes in sensitivity to the four basic tastes before and after stimulus, we found that the lower the sensitivity to the four basic tastes, the greater the increase in sensitivity induced by cold stimulus. These findings suggest that taste and low temperature send afferent signals which cause interaction in the afferent pathways between the peripheral and central nervous systems. Cold stimulus may offer one possible treatment strategy for dysgeusia. PMID- 27550338 TI - Amelogenesis imperfecta: review of diagnostic findings and treatment concepts. AB - Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option. PMID- 27550340 TI - Radiographic and functional outcomes after displaced intra-articular calcaneal fractures: a comparative cohort study among the traditional open technique (ORIF) and percutaneous surgical procedures (PS). AB - BACKGROUND: Open reduction with internal fixation (ORIF) and percutaneous surgery (PS) are the most common surgical procedures for the treatment of displaced intra articular calcaneal fractures. The purpose of this retrospective study was to compare the clinical and radiological results of these techniques and to verify the prognostic value of the radiographic measurement tools proposed in the literature. METHODS: A consecutive series of 104 calcaneal fractures was included in this analysis. Essex-Lopresti and Sanders classifications were used to evaluate the injuries, and their prognostic correlation was tested. Bohler's angle was measured pre- and postoperatively and evaluated as radiological outcome. Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society hindfoot scale (AOFAS), Maryland Foot Scale (MFS), 17-Foot Function Index (FFI), Short Form-36 (PCS), and a 10-point visual analogue scale (VAS). RESULTS: A total of 87 fractures (5 bilateral), 54 in males and 28 in females, were evaluated with a mean follow-up of 77.0 months. Overall mean age was 51.6 years old. The most frequent cause of trauma was a fall from a height. According to Essex-Lopresti, there were 58 joint depression fractures, 26 tongue, and 3 comminute. According to Sanders: 37 type II, 31 type III, and 19 type IV. Patients were divided into three groups according to surgical treatment: 19 in the ORIF group, 35 in the PS Screw group, and 33 in PS K-wire group. The ORIF group obtained significantly better results (82 AOFAS, 86 MFS, 19.6 FFI, 46.2 PCS, 8 VAS) with respect to the PS K-wire group (74 AOFAS, 76 MSF, 26.4 FFI, 40.8 PCS, 6 VAS). The PS Screw group obtained intermediate results (79 AOFAS, 82 MFS, 22.4 FFI, 41.6 PCS, 7 VAS). The restoration of the Bohler's angle was achieved most frequently (p = 0.02) in the ORIF group, without better clinical results. CONCLUSION: The results were best in the ORIF group, despite its risk of complications, inferior in the PS Screw group, however without statistical significance (p > 0.05), and worse in the PS K-wire group. Finally, our data confirmed the prognostic correlation between the two radiographic classifications used and the clinical outcomes. PMID- 27550341 TI - Impact of BNP level and peak VO2 on future heart failure events: comparison between sinus rhythm and atrial fibrillation. AB - This study aimed to examine the discrete impacts of peak oxygen consumption (VO2) and brain natriuretic peptide (BNP) levels on future heart failure (HF) events in sinus rhythm (SR) and atrial fibrillation (AF). A total of 1447 patients who underwent symptom-limited cardiopulmonary exercise testing and whose BNP values were determined simultaneously were analysed (SR, N = 1151 and AF, N = 296). HF events were defined as HF hospitalization or HF death. Over a mean follow-up period of 1472 days, 140 HF events were observed. A high BNP value (dichotomized by median value) was independently associated with HF events in SR (HR 8.08; 95 % CI 4.02-16.26; p < 0.0001), but not in AF patients (HR 1.97; 95 % CI 0.91-4.28; p = 0.087) with a significant interaction between the rhythms. By contrast, low peak VO2 was independently associated with HF events in both rhythms (AF; HR 5.81; 95 % CI 1.75-19.30; p = 0.004, SR; HR 2.04; 95 % CI 1.19-3.49; p = 0.009), with a marginal interaction between them. In bivariate Cox models, low-peak VO2 had much stronger predictive power for HF events than high-BNP in AF, whereas high-BNP was more powerful than low-peak VO2 in SR. The prognostic value of BNP and peak VO2 for future HF events seemed to be different between SR and AF. PMID- 27550342 TI - Stage-Specific Embryonic Antigen-1 (SSEA-1) Expression in Thyroid Tissues. AB - Stage-specific embryonic antigen-1 (SSEA-1), also known as CD15, is a member of a cluster of differentiation antigens that have been identified in various normal tissues and in different types of cancers including papillary and medullary thyroid carcinoma. SSEA-1 may be expressed in normal stem cells and cancer stem like cells. To evaluate the potential diagnostic and prognostic utility of SSEA-1 in thyroid tumors, we analyzed the expression of SSEA-1 in normal and neoplastic thyroid tissues by immunohistochemistry (IHC) using a tissue microarray with 158 different tissue cores. To evaluate the potential utility of SSEA-1 as a surface marker, we also assessed the expression of SSEA-1 in thyroid cell lines by flow cytometric analysis. SSEA-1 immunoreactivity was identified in malignant thyroid follicular epithelial cancers but not in the benign thyroid tissues. Anaplastic thyroid (ATC) (80 %) and conventional papillary thyroid carcinoma (PTC) (60.7 %) showed significantly higher percentage of cases that were SSEA-1 immunoreactive than follicular variant of papillary thyroid carcinoma (FVPTC) (20.6 %) and follicular carcinoma (FCA) (32.1 %). Flow cytometric analysis of cultured thyroid cell lines showed that a small subpopulation of ATC and PTC thyroid tumor cells had SSEA-1 immunoreactivity which may represent thyroid cancer stem-like cells. The ATC cells expressed more SSEA-1 immunoreactive cells than the PTC cell lines. Our findings suggest that expression of SSEA-1 immunoreactivity in thyroid neoplasms was associated with more aggressive thyroid carcinomas. SSEA-1 is a marker that detects malignant thyroid neoplasms in formalin-fixed paraffin embedded thyroid tissue sections and may be a useful marker for thyroid cancer stem-like cells. PMID- 27550343 TI - The natural history of preterm premature rupture of membranes in twin pregnancies. AB - OBJECTIVE: To compare the characteristics of preterm premature rupture of membranes (PPROM) between twin and singleton pregnancies. METHODS: This was a retrospective study of all women with twin and singleton pregnancies admitted with PPROM between 24-34 weeks of gestation. RESULTS: Overall 698 women with PPROM were eligible for the study: 101 (14.5%) twins and 597 (85.5%) singletons. Twins presented with PPROM at a more advanced gestational age compared with singletons (29.1 +/- 2.7 vs. 28.5 +/- 2.8 weeks, p = 0.03). The latency period was shorter in twins compared with singletons, especially for women presenting after 28 weeks of gestation (5.0 +/- 0.8 vs. 7.0 +/- 0.4 days, p = 0.01). Women with twins were more likely to deliver within 48 h (OR: 2.7; 95%CI: 1.7-4.2) and were less likely to deliver within 2-7 days (OR: 0.5; 95%CI: 0.3-0.9) following PPROM. The rate of clinical chorioamnionitis or placental abruption following PPROM was lower in twins compared with singletons (15.8% vs. 26.0%, p = 0.03). CONCLUSIONS: PPROM in twin pregnancies tends to occur at a more advanced gestational age, is associated with a shorter latency period and is less likely to be complicated by chorioamnionitis or placental abruption compared with singletons. This information may be useful for counseling and management decisions in cases of PPROM in women with twins. PMID- 27550344 TI - Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients. AB - Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (>=40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n = 6) and morbidly obese (n = 4) patients. The patients mean +/- standard deviation (SD) age, weight, and BMI were 54 +/- 15 years, 90 +/- 24 kg, and 31 +/- 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean +/- SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 +/- 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 +/- 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 +/- 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 +/- 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of >=2 mg/liter in patients with BMI of >30 kg/m2 A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter. PMID- 27550345 TI - Pulmonary Deposition and Elimination of Liposomal Amikacin for Inhalation and Effect on Macrophage Function after Administration in Rats. AB - Pulmonary nontuberculous mycobacterial (PNTM) infections represent a treatment challenge. Liposomal amikacin for inhalation (LAI) is a novel formulation currently in development for the treatment of PNTM infections. The pulmonary deposition and elimination of LAI and its effect on macrophage function were evaluated in a series of preclinical studies in healthy rats. The pulmonary deposition of LAI was evaluated in female rats (n = 76) treated with LAI by nebulizer at 10 mg/kg of body weight per day or 90 mg/kg per day for 27 days, followed by dosing of dually labeled LAI (LAI with a lipid label plus an amikacin label) on day 28 with subsequent lung histological and amikacin analyses. In a separate study for assessment of alveolar macrophage function, rats (n = 180) received daily treatment with LAI at 90 mg/kg per day or 1.5% saline over three 30-day treatment periods followed by 30-day recovery periods; phagocytic and Saccharomyces cerevisiae (yeast) killing capabilities and inflammatory mediator release were assessed at the end of each period. LAI demonstrated equal dose dependent deposition across all lung lobes and regions. Lipid and amikacin labels showed diffuse extracellular colocalization, followed by macrophage uptake and gradual amikacin elimination. Macrophages demonstrated accumulation of amikacin during treatment periods and nearly complete elimination during recovery periods. No evidence of an inflammatory response was seen. No differences in microsphere uptake or yeast killing were seen between LAI-treated and control macrophages. Neither LAI-treated nor control macrophages demonstrated constitutive inflammatory mediator release; however, both showed normal mediator release on lipopolysaccharide stimulation. LAI is readily taken up by macrophages in healthy rats without compromising macrophage function. PMID- 27550346 TI - Trivalency of a Nanobody Specific for the Human Respiratory Syncytial Virus Fusion Glycoprotein Drastically Enhances Virus Neutralization and Impacts Escape Mutant Selection. AB - ALX-0171 is a trivalent Nanobody derived from monovalent Nb017 that binds to antigenic site II of the human respiratory syncytial virus (hRSV) fusion (F) glycoprotein. ALX-0171 is about 6,000 to 10,000 times more potent than Nb017 in neutralization tests with strains of hRSV antigenic groups A and B. To explore the effect of this enhanced neutralization on escape mutant selection, viruses resistant to either ALX-0171 or Nb017 were isolated after serial passage of the hRSV Long strain in the presence of suboptimal concentrations of the respective Nanobodies. Resistant viruses emerged notably faster with Nb017 than with ALX 0171 and in both cases contained amino acid changes in antigenic site II of hRSV F. Detailed binding and neutralization analyses of these escape mutants as well as previously described mutants resistant to certain monoclonal antibodies (MAbs) offered a comprehensive description of site II mutations which are relevant for neutralization by MAbs and Nanobodies. Notably, ALX-0171 showed a sizeable neutralization potency with most escape mutants, even with some of those selected with the Nanobody, and these findings make ALX-0171 an attractive antiviral for treatment of hRSV infections. PMID- 27550347 TI - Activity of Tedizolid in Methicillin-Resistant Staphylococcus aureus Experimental Foreign Body-Associated Osteomyelitis. AB - We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 MUg/ml and 60 MUg . h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 MUg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin. PMID- 27550348 TI - Open-Label Study of Absorption and Clearance of 1% Voriconazole Eye Drops. AB - Twenty participants undergoing elective cataract surgery received 1% voriconazole eye drops (1 drop per eye) either 20, 40, 60, or 80 min before surgery. Median voriconazole concentrations of 1.9 to 3.2 mg/liter in aqueous humor samples were attained over the first 80 min, which were higher than in vitro MIC90 values for typical fungi that cause keratitis. PMID- 27550349 TI - Identification of Novel Cryptic Aminoglycoside Phosphotransferases in Pseudomonas aeruginosa. PMID- 27550350 TI - Transposon-Sequencing Analysis Unveils Novel Genes Involved in the Generation of Persister Cells in Uropathogenic Escherichia coli. AB - Persister cells are highly tolerant to different antibiotics and are associated with relapsing infections. In order to understand this phenomenon further, we exposed a transposon library to a lethal concentration of ampicillin, and mutants that survived were identified by transposon sequencing (Tn-Seq). We determined that mutations related to carbon metabolism, cell envelope (cell wall generation and membrane proteins), and stress response have a role in persister cell generation. PMID- 27550351 TI - Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation. AB - Ceftolozane-tazobactam has potent activity against Pseudomonas aeruginosa, a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for the ceftolozane component at 1.5 g and 3 g of ceftolozane-tazobactam q8h across a range of MICs using a primary threshold exposure of 60% free time above the MIC (fT>MIC). In these 20 adult CF patients, ceftolozane and tazobactam concentration data were best described by 2 compartment models, and ceftolozane clearance (CL) was significantly correlated with creatinine clearance (r = 0.71, P < 0.001). These data suggest that ceftolozane and tazobactam clearance estimates in CF patients are similar to those in adults without CF (ceftolozane CF CL, 4.76 +/- 1.13 liter/h; tazobactam CF CL, 20.51 +/- 4.41 liter/h). However, estimates of the volume of the central compartment (Vc) were lower than those for adults without CF (ceftolozane CF Vc, 7.51 +/- 2.05 liters; tazobactam CF Vc, 7.85 +/- 2.66 liters). Using a threshold of 60% fT>MIC, ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of >=90% at MICs up to 4 and 8 MUg/ml, respectively. Ceftolozane tazobactam at 3 g q8h was well tolerated. These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02421120.). PMID- 27550352 TI - Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein Based Cell-Cell Fusion Assay. AB - Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2. PMID- 27550353 TI - Sequence Type 48 Escherichia coli Carrying the blaCTX-M-1 IncI1/ST3 Plasmid in Drinking Water in France. AB - Drinking water has rarely been recognized as a source of antimicrobial resistance for humans, and only in low-income countries. Here, a sequence type 48 Escherichia coli isolate carrying the blaCTX-M-1 IncI1/ST3 plasmid was recovered from drinking water in France. This plasmid was similar to other blaCTX-M-1 IncI1/ST3 plasmids found previously in animals and humans. Our findings highlight the possible human transfer of extended-spectrum beta-lactamase (ESBL) genes through drinking water in high-income countries. PMID- 27550354 TI - Inhibitory Interaction Potential of 22 Antituberculosis Drugs on Organic Anion and Cation Transporters of the SLC22A Family. AB - Twenty-two currently marketed antituberculosis drugs were comprehensively evaluated for their inhibitory effect on organic anionic transporter (OAT)- and organic cation transporter (OCT)-mediated uptake using stably transfected HEK293 cells in vitro We observed moderate to strong inhibitory effects on OAT1- and OAT3-mediated para-aminohippurate (PAH) uptake and OCT1- and OCT2-mediated N methyl-4-phenylpylidinium acetate (MPP+) uptake. Ciprofloxacin, linezolid, para aminosalicylic acid (PAS), and rifampin were observed to have strong inhibitory effects, with the concentrations for a 50% inhibitory effect (IC50s) being 35.1, 31.1, 37.6, and 48.1 MUM, respectively, for OAT1 and >100, 21.9, 24.6, and 30.2 MUM, respectively, for OAT3. Similarly, pyrazinamide, rifabutin, and levofloxacin were observed to have inhibitory effects, with IC50 values being 36.5, 42.7, and 30.3 MUM, respectively, for OCT1 and with the IC50 value for PAS being 94.2 MUM for OCT2. In addition, we used zidovudine and metformin as clinically prescribed substrates of OATs and OCTs, respectively, and zidovudine and metformin uptake was also strongly inhibited by the antituberculosis drugs. Among the tested drugs, the highest drug-drug interaction (DDI) indexes were found for PAS, which were 9.3 to 13.9 for OAT1 and 12.0 to 17.7 for OAT3, and linezolid, which were 1.18 to 2.15 for OAT1 and 1.7 to 3.01 for OAT3. Similarly, the DDI indexes of pyrazinamide and levofloxacin were 0.57 and 0.30, respectively, for OCT1, and the DDI index of PAS was 3.8 for OCT2, suggesting a stronger possibility (DDI index value cutoff, >0.1) of in vivo DDIs. This is the first comprehensive report of the inhibitory potential of anti-TB drugs on OAT- and OCT-mediated uptake of prototype and clinically prescribed substrate drugs in vitro, providing an ability to predict DDIs between anti-TB drugs and other coprescribed drugs in clinical studies in vivo. PMID- 27550356 TI - In Vitro Bactericidal Activity of Trimethoprim-Sulfamethoxazole Alone and in Combination with Colistin against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates. AB - Trimethoprim-sulfamethoxazole alone and combined with colistin was tested in vitro against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections. PMID- 27550355 TI - Modulation of the Substitution Pattern of 5-Aryl-2-Aminoimidazoles Allows Fine Tuning of Their Antibiofilm Activity Spectrum and Toxicity. AB - We previously synthesized several series of compounds, based on the 5-aryl-2 aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1- and 2N-substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N substituted compounds were nontoxic and active against biofilms formed by Gram negative bacteria and C. albicans but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1 ,2N-disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity. PMID- 27550357 TI - Dual Targeting of Cell Wall Precursors by Teixobactin Leads to Cell Lysis. AB - Teixobactin represents the first member of a newly discovered class of antibiotics that act through inhibition of cell wall synthesis. Teixobactin binds multiple bactoprenol-coupled cell wall precursors, inhibiting both peptidoglycan and teichoic acid synthesis. Here, we show that the impressive bactericidal activity of teixobactin is due to the synergistic inhibition of both targets, resulting in cell wall damage, delocalization of autolysins, and subsequent cell lysis. We also find that teixobactin does not bind mature peptidoglycan, further increasing its activity at high cell densities and against vancomycin intermediate Staphylococcus aureus (VISA) isolates with thickened peptidoglycan layers. These findings add to the attractiveness of teixobactin as a potential therapeutic agent for the treatment of infection caused by antibiotic-resistant Gram-positive pathogens. PMID- 27550359 TI - Eravacycline Is Active against Bacterial Isolates Expressing the Polymyxin Resistance Gene mcr-1. PMID- 27550358 TI - Clarithromycin Suppresses Chloride Channel Accessory 1 and Inhibits Interleukin 13-Induced Goblet Cell Hyperplasia in Human Bronchial Epithelial Cells. AB - Activation of the interleukin-13 (IL-13) receptor leads to signal transducer and activator of transcription 6 (STAT6) activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF) and chloride channel accessory 1 (CLCA1), increasing secretion of the gel-forming mucin MUC5AC. Activation of the epidermal growth factor receptor (EGFR) also leads to MUC5AC production via extracellular signal-regulated kinase (ERK1/2). We examined the effect of clarithromycin IL-13 signaling leading to production. Normal human bronchial epithelial (NHBE) cells were grown for 14 days at an air-liquid interface (ALI) with IL-13 and/or clarithromycin. Histochemical analysis was performed using hematoxylin and eosin (HE) staining and MUC5AC immunostaining. MUC5AC, SPDEF, and CLCA1 mRNA expression were evaluated by real-time PCR. Western analysis was used to assess phosphorylation of STAT6 and ERK1/2. Clarithromycin decreased IL-13-induced goblet cell hyperplasia and MUC5AC mRNA expression in a dose-dependent manner. Clarithromycin decreased IL-13-stimulated SPDEF and CLCA1 mRNA expression in a dose-dependent manner, and at 32 MUg/ml CLCA1 was profoundly decreased (P < 0.001). Although clarithromycin had no effect on STAT6 phosphorylation induced by IL-13, it decreased constitutive phosphorylation of ERK1/2 (P < 0.05). PMID- 27550360 TI - Rapid Detection of FKS-Associated Echinocandin Resistance in Candida glabrata. AB - A novel and highly accurate diagnostic assay platform was established for rapid identification of FKS mutations associated with echinocandin resistance in Candida glabrata The assay platform uses allele-specific molecular beacon and DNA melt analysis following asymmetric PCR. A dual assay for FKS1 and FKS2 was developed to identify within 3 h the most common and clinically relevant resistance-associated mutations, including 8 FKS1 HS1 (wild type [WT], S629P, F625S, D632Y, D632E [T1896G], D632E [T1896A], I634V, and F625F) and 7 FKS2 HS1 (WT, F659del, F659S, F659V, F659L, S663P, and S663F) genotypes. A blinded panel of 188 C. glabrata clinical isolates was tested by both assays. The molecular diagnostic results from the dual assay were 100% concordant with data obtained from DNA sequencing. This platform has the potential to overcome the deficiencies of existing in vitro susceptibility-based assays to identify echinocandin resistant C. glabrata and holds promise as a surrogate diagnostic method to better direct echinocandin therapy. PMID- 27550361 TI - Early Bactericidal Activity of AZD5847 in Patients with Pulmonary Tuberculosis. AB - AZD5847 is an oxazolidinone antibiotic with in vitro activity against Mycobacterium tuberculosis The objective of this study was to evaluate the antimycobacterial activity, safety, and pharmacokinetics of AZD5847 in patients with pulmonary tuberculosis. Groups of 15 treatment-naive, sputum smear-positive adults with pulmonary tuberculosis were randomly assigned to receive AZD5847 at one of four doses (500 mg once daily, 500 mg twice daily, 1,200 mg once daily, and 800 mg twice daily) or daily standard chemotherapy. The primary efficacy endpoint was the mean daily rate of change in the log10 number of CFU of M. tuberculosis per milliliter of sputum, expressed as the change in log10 number of CFU per milliliter of sputum per day. The mean 14-day activity of the combination of isoniazid, rifampin, ethambutol, and pyrazinamide (-0.163 log10 CFU/ml sputum/day; 95% confidence interval [CI], -0.193, -0.133 log10 CFU/ml sputum/day) was consistent with that found in previous studies. AZD5847 at 500 mg twice daily significantly decreased the number of CFU on solid medium (-0.039; 95% CI, 0.069, -0.009; P = 0.0048). No bactericidal activity was detected at doses of AZD5847 of 500 mg once daily (mean early bactericidal activity [EBA], 0.02 [95% CI, -0.01, 0.05]), 1,200 mg once daily (mean EBA, 0.02 [95% CI, -0.01, 0.05]), and 800 mg twice daily (mean EBA, 0.02 [95% CI, -0.01, 0.05]). AZD5847 at doses of both 500 mg and 800 mg twice daily also showed an increase in the time to a positive culture in MGIT liquid culture medium. Two serious adverse events (grade 4 thrombocytopenia and grade 4 hyperbilirubinemia) occurred in patients receiving AZD5847 at higher doses. AZD5847 dosed twice daily kills tubercle bacilli in the sputum of patients with pulmonary tuberculosis and has modest early bactericidal activity. (This study has been registered at ClinicalTrials.gov under registration no. NCT01516203.). PMID- 27550362 TI - Systematic Review and Meta-analysis of the Pharmacokinetics of Benznidazole in the Treatment of Chagas Disease. AB - Chagas disease is a neglected parasitic illness affecting approximately 8 million people, predominantly in Latin America. Benznidazole is the drug of choice for treatment, although its availability has been limited. A paucity of knowledge of the pharmacokinetic properties of this drug has contributed to its limited availability in several jurisdictions. The objective of this study was to conduct a systematic literature review and a Bayesian meta-analysis of pharmacokinetic studies to improve estimates of the basic pharmacokinetic properties of benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO (Scientific Electronic Library Online) databases was conducted. Eligible studies reported patient-level data from single-100-mg-dose pharmacokinetic evaluations of benznidazole in adults or otherwise provided data relevant to the estimation of pharmacokinetic parameters which could be derived from such studies. A Bayesian hierarchical model was used for analysis. Secondary data (i.e., data from studies that did not include patient-level, single-100-mg-dose data) were used for the generation of empirical priors for the Bayesian analysis. The systematic search identified nine studies for inclusion. Nine pharmacokinetic parameters were estimated, including the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (Cmax), the time to Cmax, the elimination rate constant (kel), the absorption rate constant (Ka), the absorption and elimination half-lives, the apparent oral clearance, and the apparent oral volume of distribution. The results showed consistency across studies. AUC and Cmax were 51.31 mg . h/liter (95% credible interval [CrI], 45.01, 60.28 mg . h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter), respectively. Ka and kel were 1.16 h-1 (95% CrI, 0.59, 1.76 h-1) and 0.052 h-1 (95% CrI, 0.045, 0.059 h-1), respectively, with the corresponding absorption and elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI, 11.79, 15.42 h), respectively. The oral clearance and volume of distribution were 2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58, 42.17 liters), respectively. A Bayesian meta-analysis was used to improve the estimates of the standard pharmacokinetic parameters of benznidazole. These data can inform clinicians and policy makers as access to this drug increases. PMID- 27550364 TI - Emergence of NDM-5- and MCR-1-Producing Escherichia coli Clones ST648 and ST156 from a Single Muscovy Duck (Cairina moschata). AB - Two Escherichia coli clones (sequence type 648 [ST648] and ST156) that coproduce NDM-5 and MCR-1 were detected from a single fowl in China. The blaNDM-5 gene was found on the two indistinguishable IncX3 plasmids from the two different E. coli isolates, whereas the mcr-1 gene was located on IncHI2 and IncI2 plasmids, respectively, suggesting that blaNDM-5 and mcr-1 have spread in avian intestinal flora. Also, the two strains harbor blaTEM-1, blaCTX-M-55, fosA3, and aac(6')-Ib The multiresistant E. coli strains (especially the epidemic clone ST648) might raise a potential threat to human health via food chain transmission. PMID- 27550363 TI - Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection. AB - Despite current prophylactic strategies, sexually transmitted infections (STIs) remain significant contributors to global health challenges, spurring the development of new multipurpose delivery technologies to protect individuals from and treat virus infections. However, there are few methods currently available to prevent and no method to date that cures human immunodeficiency virus (HIV) infection or combinations of STIs. While current oral and topical preexposure prophylaxes have protected against HIV infection, they have primarily relied on antiretrovirals (ARVs) to inhibit infection. Yet continued challenges with ARVs include user adherence to daily treatment regimens and the potential toxicity and antiviral resistance associated with chronic use. The integration of new biological agents may avert some of these adverse effects while also providing new mechanisms to prevent infection. Of the biologic-based antivirals, griffithsin (GRFT) has demonstrated potent inhibition of HIV-1 (and a multitude of other viruses) by adhering to and inactivating HIV-1 immediately upon contact. In parallel with the development of GRFT, electrospun fibers (EFs) have emerged as a promising platform for the delivery of agents active against HIV infection. In the study described here, our goal was to extend the mechanistic diversity of active agents and electrospun fibers by incorporating the biologic GRFT on the EF surface rather than within the EFs to inactivate HIV prior to cellular entry. We fabricated and characterized GRFT-modified EFs (GRFT-EFs) with different surface modification densities of GRFT and demonstrated their safety and efficacy against HIV-1 infection in vitro We believe that EFs are a unique platform that may be enhanced by incorporation of additional antiviral agents to prevent STIs via multiple mechanisms. PMID- 27550366 TI - Differential frontal theta activity during cognitive and motor tasks. AB - The present study investigated psychophysiological differences between cognitive and motor tasks. Participants were 16 university students (male[Formula: see text][Formula: see text][Formula: see text]10, female[Formula: see text][Formula: see text][Formula: see text]6) aged between 24 to 31 years (mean[Formula: see text][Formula: see text][Formula: see text]27.6 years, SD[Formula: see text][Formula: see text] [Formula: see text] years). They were instructed to perform cognitive and motor tasks while their brain activity was simultaneously recorded using electroencephalography (EEG). A 3(task)[Formula: see text][Formula: see text][Formula: see text]8(area)[Formula: see text][Formula: see text][Formula: see text]4(bands) analysis of variance (ANOVA) was performed on theta, alpha and beta frequency bands. The results showed that the cognitive task resulted in a significantly higher spectral power in the theta band at frontal electrodes than did the motor task. This suggests that the frontal lobe might be engaged in problem solving, resulting in increased theta activity. However, there were no differences in alpha and beta activity between the two tasks. The present study provides psychophysiological evidence for classifying cognitive and motor tasks, which has been a controversial issue for task classifications in motor learning research. PMID- 27550365 TI - Alterations in the Emotional Regulation Process in Gambling Addiction: The Role of Anger and Alexithymia. AB - This study aims at the assessment of alexithymia and anger levels in 100 treatment-seeking pathological gamblers compared with controls, who were matched for age, gender and education. Furthermore a positive correlation between alexithymia, anger and severity of gambling disorder and a relationship between gambling behaviour and anger after controlling for alexithymia, are investigated. Finally the role that gender plays in anger in pathological gamblers was also evaluated. Psychological assessment includes the South Oaks Gambling Screen, State-Trait Anger Expression Inventory-2 and the twenty-item Toronto Alexithymia Scale. Statistical analysis of the results shows a higher level of anger in pathological gamblers than in controls, together with alterations in emotional processing. Severity of gambling behaviour positively correlates with alexithymia scores, state-anger and trait-anger. Moreover, a significant contribution of anger in predicting gambling behaviour was suggested after controlling for alexithymia. In conclusion, anger and alexithymia must be regarded as relevant components of the assessment of pathological gamblers, in order to select the best therapeutical strategies to prevent self-defeating behaviours and to reduce drop-out from treatments. PMID- 27550367 TI - Factors influencing participation in colorectal cancer screening-a qualitative study in an ethnic and socio-economically diverse inner city population. AB - BACKGROUND: Ethnic and socio-economic inequalities have been reported in the uptake of colorectal cancer (CRC) screening. This study aimed to explore the factors affecting CRC screening participation in an ethnically and socio economically diverse inner city population. METHODS: Semi-structured interviews were undertaken with 50 people aged 55-74 years, recruited from GP practices in south-east London. Participants were from Black African (n=13), Black Caribbean (n=15), White British (n=17), Black other (n=2) and White other (n=3) backgrounds. Participants' socio-economic status (SES) was assessed using a combined measure of educational attainment, housing tenure and car ownership. Participants' SES varied although there were more participants from less deprived backgrounds than those from more deprived backgrounds. The interview topic guide was informed by the Theoretical Domains Framework. Interviews were recorded, transcribed and analysed using framework analysis. FINDINGS: Lack of awareness of CRC screening was a barrier for all participants. There were also some notable group differences by ethnicity and SES. Cancer fear was a barrier for White British participants of varying SES. Misunderstanding instructions for completing the guaiac faecal occult blood test (gFOBt) was a barrier for people of low SES regardless of ethnicity. For Black African and Black Caribbean participants, of any SES, religious faith and a perceived civic duty to participate in screening encouraged participation. DISCUSSION AND CONCLUSIONS: This is the first study to provide detailed information on the separate views of Black African and Black Caribbean participants about screening. Consideration of ethnicity and SES together also allowed us to identify pertinent barriers for particular groups that can be targeted to improve access to screening for those who wish to take part. PMID- 27550368 TI - Multiple virus infection in a single strain of Fusarium poae shown by deep sequencing. AB - Many bands were detected on an electrophoretic profile of double-stranded (ds) RNA preparation from a single strain of Fusarium poae isolated from wheat. When the purified dsRNA sample was deep-sequenced by a next-generation sequencer, sixteen virus-like assembled contigs with predicted amino acid sequences showing homologies to respective viral RNA-dependent RNA polymerases (RdRps) were found by BLAST analysis. Fourteen out of sixteen sequences showed homologies to RdRps of known mycoviruses, that is, four mitoviruses, two narnaviruses, two partitiviruses, an alternavirus, a fusarivirus, a hypovirus, a victorivirus, and two unclassified mycoviruses, Sclerotinia sclerotiorum dsRNA mycovirus-L and Aspergillus foetidus slow virus 2, respectively. The other two putative viral RdRp sequences showed homologies to those of members of negative-stranded RNA viruses, the Ophiovirus and the Phlebovirus respectively, which mycoviruses had been not ever assigned to. Based on genome structure and phylogenetic analysis, both viruses were thought to be members of novel respective negative-stranded RNA virus groups. The presences of all sixteen viral RdRp sequences identified by BLAST analysis were confirmed by sequencing RT-PCR products generated from the starting dsRNA material using primers designed from the de novo assembled sequences of respective putative mycoviruses. Since the single strain of F. poae was considered to be multiply infected with mycoviruses from novel taxonomical groups in addition to many common mycoviruses, the RNA virome of the strain was found to be highly diverse. PMID- 27550369 TI - Low genetic diversity of Banana bunchy top virus, with a sub-regional pattern of variation, in Democratic Republic of Congo. AB - Banana bunchy top virus (BBTV), belonging to the genus Babuvirus, is the most devastating and widespread banana virus. Banana and plantain are major crops in terms of household income and food security in Democratic Republic of Congo (DRC). Despite the large area under banana and plantain cultivation in the country, before this study, the genetic characterization of BBTV isolates had only been undertaken for two provinces. In the study presented here, genetic variation in BBTV was assessed from 52 BBTV isolates collected in five out of 11 provinces in DRC (Bandundu, Bas-Congo, Katanga, Kinshasa and Kasai Oriental) and in two provinces using sequences previously described in databases. Full genome sequencing of DNA-R components was performed, revealing low genetic variation (98 100 % nucleotide identity) among the BBTV isolates detected. The phylogenetic analyses showed that all the DRC isolates were clustered in the South Pacific clade of BBTV. Based on the coding region for the replication initiator protein, haplotype diversity was estimated to be 0.944 +/- 0.013, with 30 haplotypes from 68 isolates in DRC. Such diversity shows a haplotype distribution mainly at the sub-regional level in DRC. In addition, the sequence determination from the whole genome of selected isolates confirmed low genetic variation among isolates from seven DRC provinces (97-100 % nucleotide identity). This study strengthened the hypothesis of a single BBTV introduction some time ago, followed by the spread of the virus in the country. PMID- 27550370 TI - Shedding light on the role of circadian disruption in breast cancer etiology. PMID- 27550372 TI - Is Dietary Red Meat Kidney Toxic? PMID- 27550371 TI - Tolerability and Safety Profile of Cariprazine in Treating Psychotic Disorders, Bipolar Disorder and Major Depressive Disorder: A Systematic Review with Meta Analysis of Randomized Controlled Trials. AB - BACKGROUND: Cariprazine is a novel antipsychotic agent recently approved for treating schizophrenia and bipolar mania in the USA. The sample sizes of published randomized controlled trials (RCTs) of the drug are small; previous meta-analyses included few RCTs and did not specifically investigate the tolerability/safety profile of cariprazine. OBJECTIVE: Our objective was to conduct a meta-analysis of published RCTs to systematically review the tolerability and safety of cariprazine versus placebo. METHODS: We searched the clinical trial registers (the metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform) and electronic databases (PubMed, Embase, PsycINFO and Cochrane library) up to June 2016 to identify phase II/III RCTs of cariprazine in patients with schizophrenia, bipolar disorder or major depressive disorder. We conducted a meta-analysis to investigate outcomes, including risks of discontinuation due to adverse events (AEs), extrapyramidal side effects (EPS) or related events, metabolic syndrome and cardiovascular-related events. RESULTS: We included nine RCTs, with a total of 4324 subjects. The risk of discontinuation due to AEs for cariprazine was similar to that for placebo (risk ratio [RR] 1.13, 95 % confidence interval [CI] 0.77-1.66). Cariprazine was associated with higher risks of EPS-related events than was placebo, including risk of akathisia (RR 3.92, 95 % CI 2.83-5.43), tremor (RR 2.41, 95 % CI 1.53-3.79) and restlessness (RR 2.17, 95 % CI 1.38-3.40). The cariprazine treatment group was more likely to have clinically significant weight gain (RR 1.68, 95 % CI 1.12-2.52). No statistically significant differences in results were found in other metabolic parameters or cardiovascular-related events. CONCLUSION: There was a statistically significant higher risk of EPS-related AEs and a slight increase in mean body weight with cariprazine. There were no statistically significant effects on prolactin level or cardiovascular parameters. EPSs were the main short term adverse reactions reported in the limited number of patients studied. Further clinical and post-marketing pharmacovigilance studies are needed to investigate the long-term safety of cariprazine. PMID- 27550373 TI - The Dok-3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor-independent manner. AB - The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by the virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here, we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells. In the absence of coreceptor ligation, SHIP translocates to sites of BCR activation through a concerted action of the protein adaptor unit Dok-3/Grb2 and phosphorylated BCR signaling components. Our data reveal auto-inhibitory SHIP activation by the activated BCR and suggest an unexpected negative-regulatory capacity of immunoreceptor tyrosine-based activation motifs in Igalpha and Igbeta. PMID- 27550374 TI - "It comes down to just how human someone can be": A qualitative study with young people from refugee backgrounds about their experiences of Australian mental health services. AB - While much literature documents the mental health needs of young people from refugee backgrounds, and the barriers they face in accessing mental health services, researchers have yet to document the perspectives of service users from this population about their contacts with clinicians and services. We therefore individually interviewed 16 young people (aged 18-25 years) who were refugees about their experiences of seeing mental health professionals. Participants were born in 9 different countries and had lived in Australia for an average of 5.2 years. They placed most emphasis on in-session factors, and particularly on interpersonal considerations. Among the main themes identified via thematic analysis were the practitioner's sensitivity to the young person's cultural background and to the stressors affecting him or her, including traumatic refugee experiences, and the therapeutic relationship-especially the qualities of trust, understanding, respect, and a caring connection. The participants had diverse reactions to treatment strategies. They emphasised the role of their preconceptions around mental health services, and called for systematic mental health awareness-raising for young people from refugee backgrounds. Implications for research, policy, and practice are discussed with a focus on findings that may guide efforts to improve service acceptability, accessibility, and effectiveness. In particular, there is a need for practitioners to attend to their clients' experiences of sessions, to adopt an attuned, contextualised, systemic approach, and especially to take a nuanced approach to cultural sensitivity. PMID- 27550375 TI - Force-field parameters for beryllium complexes in amorphous layers. AB - Unknown force-field parameters for metal organic beryllium complexes used in emitting and electron transporting layers of OLED structures are determined. These parameters can be used for the predictive atomistic simulations of the structure and properties of amorphous organic layers containing beryllium complexes. The parameters are found for the AMBER force field using a relaxed scan procedure and quantum-mechanical DFT calculations of potential energy curves for specific internal (angular) coordinates in a series of three Be complexes (Bebq2; Be(4-mpp)2; Bepp2). The obtained parameters are verified in calculations of some molecular and crystal structures available from either quantum-mechanical DFT calculations or experimental data. Graphical Abstract Beryllium complexes in amorphous layers?. PMID- 27550376 TI - What Is a Lactation Professional? PMID- 27550378 TI - Factors Associated with Infant Feeding Choices in the Adolescent Population. AB - BACKGROUND: Strong recommendations have been made for exclusive breastfeeding of infants for the first 6 months of life, with continuation throughout the first year. In an attempt to optimize support for breastfeeding, particular barriers in populations with decreased rates need to be analyzed. OBJECTIVE: This study aimed to determine if participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food voucher program, involvement of the infant's father, involvement of the adolescent mother's parents or other caregivers, and participation in early skin-to-skin contact after birth are associated with the decision to breastfeed or bottle feed among this adolescent population. METHODS: A retrospective chart review of 457 adolescent patients who delivered January 2010 through May 2013 at the University of Louisville Hospital was conducted. Nursing documentation was used to determine the patient's intention to breastfeed or bottle feed, participation in WIC, involvement of the infant's father, involvement of the patient's parents, and participation in early skin-to-skin contact after delivery. These factors were compared using Fisher exact test. RESULTS: Three hundred one adolescents reported a plan to breastfeed (65.9%) and 156 reported a plan to bottle feed (34.1%) when questioned pre delivery. There was no significant difference between the groups with respect to WIC participation or involvement of the infant's father. The bottle-feeding group had a significantly higher percentage who reported parental involvement (80.1% vs 67.8%, P = .0059). The breastfeeding group had a significantly higher percentage who participated in early skin-to-skin contact after birth (74.5% vs 58.1%, P = .0064). CONCLUSION: Involvement of the adolescent mothers' parents or caregivers was associated with the decision to bottle feed. Participation in early skin-to skin contact after birth was associated with the decision to breastfeed. PMID- 27550377 TI - Early Lactation and Infant Feeding Practices Differ by Maternal Gestational Diabetes History. AB - BACKGROUND: Detailed data on lactation practices by gestational diabetes mellitus (GDM) history are lacking, precluding potential explanations and targets for interventions to improve lactation intensity and duration and, ultimately, long term maternal and child health. OBJECTIVE: This study aimed to examine breastfeeding practices through 12 months postpartum by GDM history. METHODS: Women who delivered a singleton, liveborn infant at The Ohio State University Wexner Medical Center (Columbus, OH), in 2011 completed a postal questionnaire to assess lactation and infant feeding practices and difficulties. Bivariate and multivariate associations between GDM history and lactation and infant feeding practices were examined. RESULTS: The sample included 432 women (62% response rate), including 7.9% who had GDM during the index pregnancy. Women with GDM initiated breastfeeding (at-the-breast or pumping) as often as women without any diabetes but were more likely to report introduction of formula within the first 2 days of life (79.4% vs 53.8%, P < .01; adjusted odds ratio: 3.48; 95% confidence interval, 1.47-8.26). Women with GDM initiated pumping 4 days earlier than women without diabetes ( P < .05), which was confirmed in adjusted analyses. There was no difference in the proportion of women reporting breastfeeding difficulty (odds ratio: 2.08; 95% confidence interval, 0.78-5.52). However, there was a trend toward women with GDM reporting more formula feeding and less at-the breast feeding as strategies to address difficulty compared with women without diabetes. CONCLUSION: Additional research is needed to understand why women with GDM engage in different early lactation and infant feeding practices, and how best to promote and sustain breastfeeding among these women. PMID- 27550380 TI - Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small Molecule Inhibitor of Eg5. AB - Due to their fast and often reversible mode of action, small molecules are ideally suited to dissect biological processes. Yet, the validity of small molecule studies is intimately tied to the specificity of the applied compounds, thus imposing a great challenge to screens for novel inhibitors. Here, we applied a chemical-genetics approach to render kinesin motor proteins sensitive to inhibition by the well-characterized small molecule S-Trityl-l-cysteine (STLC). STLC specifically inhibits the kinesin Eg5 through binding to a known allosteric site within the motor domain. Transfer of this allosteric binding site into the motor domain of the human kinesins Kif3A and Kif4A sensitizes them towards STLC. Single-molecule microscopy analyses confirmed that STLC inhibits the movement of chimeric but not wild-type Kif4A along microtubules. Thus, our proof-of-concept study revealed that this chemical-genetic approach provides a powerful strategy to specifically inhibit kinesins in vitro for which small-molecule inhibitors are not yet available. PMID- 27550379 TI - Stakeholders' views on the ethical challenges of pragmatic trials investigating pharmaceutical drugs. AB - BACKGROUND: We explored the views of key stakeholders to identify the ethical challenges of pragmatic trials investigating pharmaceutical drugs. A secondary aim was to capture stakeholders' attitudes towards the implementation of pragmatic trials in the drug development process. METHODS: We conducted semistructured, in-depth interviews among individuals from different key stakeholder groups (academia and independent research institutions, the pharmaceutical industry, regulators, Health Technology Assessment (HTA) agencies and patients' organizations) through telephone or face-to-face sessions. Interviews were structured around the question "what challenges were experienced or perceived during the design, conduct and/or review of pragmatic trials." Respondents were additionally asked about their views on implementation of pragmatic trials in the drug development process. Thematic analysis was used to identify the ethically relevant features across data sets. RESULTS: We interviewed 34 stakeholders in 25 individual sessions and four group sessions. The four perceived challenges of ethical relevance were: (1) less controlled conditions creating safety concerns, (2) comparison with usual care potentially compromising clinical equipoise, (3) tailored or waivers of informed consent affecting patient autonomy, and (4) minimal interference with "real-world" practice reducing the knowledge value of trial results. CONCLUSIONS: We identified stakeholder concerns regarding risk assessment, use of suboptimal usual care as a comparator, tailoring of informed consent procedures and ensuring the social value of pragmatic trials. These concerns increased when respondents were asked about pragmatic trials conducted before market authorization. PMID- 27550381 TI - Entropic Phase Transitions with Stable Twisted Intermediates of Bio-Inspired Self Assembly. AB - Controlling the hierarchical process and capturing the intermediate stage underlying bio-inspired self-assembly are pivotal for understanding their aggregation mechanism and exploring possible applications. Here, the self assembly of a designed minimal lipopeptide was characterized, showing it to initially self-assemble to narrow nanotwists, which then ripen to wide nanotwists, and finally transit to hollow nanotubes. The supramolecular phase transitions were revealed to be driven by entropic hydrophobic interactions, rather than by the common mechanism of enthalpy-related contributions. The transformation dynamics were sufficiently slow to enable detection and characterization of each stage, thus inducing the stable and extensive distributions of twisted intermediates. The findings allow an in-depth understanding of the hierarchical self-association of bio-inspired building blocks and provide a new approach for the preparation of superstructures of unique morphologies. PMID- 27550382 TI - Interaction of gold nanoparticles and nickel(II) sulfate affects dendritic cell maturation. AB - Despite many investigations have focused on the pristine toxicity of gold nanoparticles (GNPs), little is known about the outcome of co-exposure and interaction of GNPs with heavy metals which can possibly detoxify or potentiate them. Here, the combined exposure of nickel (II) sulfate (NiSO4) and GNPs on the maturation response of dendritic cells (DCs) was explored. Exposure to GNPs or NiSO4 separately induced cell activation. When cells were exposed to a mixture of both, however, the observed cell activation pattern indicated a competitive rather than an additive effect of both inducers with levels similar to those induced by NiSO4 alone. Quantification of the GNP uptake by DCs demonstrated a significant decrease in intracellular gold content during co-incubation with NiSO4. An extensive physiochemical characterization was performed to determine the interaction between GNPs and NiSO4 in the complex physiological media using nanoparticle tracking analyses, disc centrifugation, UV-visible spectroscopy, ICP MS analyses, zeta potential measurements, electron microscopy, and proteomics. Although GNPs and NiSO4 did not directly interact with each other, the presence of NiSO4 in the physiological media resulted in changes in GNPs' charge and their associated protein corona (content and composition), which may contribute to a decreased cellular uptake of GNPs and sustaining the nickel-induced DC maturation. The presented results provide new insights in the interaction of heavy metals and NPs in complex physiological media. Moreover, this study highlights the necessity of mixture toxicology, since these combined exposures are highly relevant for human subjection to NPs and risk assessment of nanomaterials. PMID- 27550384 TI - Site-specific control of multiple mineralizations using a designed peptide and DNA. AB - We have developed a site-specific method for precipitating multiple inorganic compounds using target DNA and a designed peptide consisting of a peptide nucleic acid (PNA) sequence and an inorganic compound-precipitating sequence. This system for controlled site-specific precipitation represents a powerful tool for use in nanobiotechnology and materials science. PMID- 27550383 TI - Inhibition of endoplasmic reticulum stress improves coronary artery function in the spontaneously hypertensive rats. AB - Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of cardiovascular complications. However, the role and mechanisms of ER stress in hypertension remain unclear. Thus, we hypothesized that enhanced ER stress contributes to the maintenance of hypertension in spontaneously hypertensive rats (SHRs). Sixteen-week old male SHRs and Wistar Kyoto Rats (WKYs) were used in this study. The SHRs were treated with ER stress inhibitor (Tauroursodeoxycholic acid; TUDCA, 100 mg/kg/day) for two weeks. There was a decrease in systolic blood pressure in SHR treated with TUDCA. The pressure induced myogenic tone was significantly increased, whereas endothelium-dependent relaxation was significantly attenuated in SHR compared with WHY. Interestingly, treatment of ER stress inhibitor normalized myogenic responses and endothelium dependent relaxation in SHR. These data were associated with an increase in expression or phosphorylation of ER stress markers (Bip, ATF6, CHOP, IRE1, XBP1, PERK, and eIF2alpha) in SHRs, which were reduced by TUDCA treatment. Furthermore, phosphorylation of MLC20 was increased in SHRs, which was reduced by the treatment of TUDCA. Therefore, our results suggest that ER stress could be a potential target for hypertension. PMID- 27550385 TI - Preferences for long-term follow-up care in childhood cancer survivors. AB - Follow-up care is important for childhood cancer survivors to facilitate early detection and treatment of late effects. We aimed to describe preferences for different organisational aspects and models of follow-up care among Swiss childhood cancer survivors, and characteristics associated with preferences for different models. We contacted 720 survivors aged 18+ years, diagnosed with cancer after 1990 (age 0-16 years), registered in the Swiss Childhood Cancer Registry (SCCR), and Swiss resident, who previously participated in a baseline survey. They received questionnaires to assess attendance and preferences for follow-up (rated on 4-point scales, 0-3). Clinical information was available from the SCCR. Survivors (n = 314: response rate 43.6%; 47.8% still attended follow up) rated clinical reasons for follow-up higher than supportive reasons (p < .001). They rated checking for cancer recurrence (mean = 2.78, SD = 0.53) and knowing about risks for my children most important (mean = 2.22, SD = 0.83). They preferred to attend a children's hospital (mean = 1.94, SD = 1.11), adult hospital (mean = 1.86, SD = 0.98) or general practitioner (mean = 1.86, SD = 1.01) rather than a central specialised late effects clinic (mean = 1.25, SD = 1.06, p < .001), and be seen by paediatric (mean = 2.24, SD = 0.72) or medical oncologist (mean = 2.17, SD = 0.69). Survivors preferred decentralised clinic based follow-up, rather than one central specialised late effects clinic. Survivors' preferences should be considered to ensure future attendance. PMID- 27550386 TI - Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes. AB - AIMS: To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes. MATERIALS AND METHODS: In this single centre, double-blind trial, we randomized 50 obese adults without diabetes (aged 18-70 years; body mass index 30-45 kg/m2 ) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately. RESULTS: Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was -4.13 kg (95% confidence interval -6.44, -1.81; P < .001), which was mostly attributable to adipose tissue reduction without lean tissue change; 36.0% versus 4.2% of participants achieved >=5% body weight loss, respectively; and prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P < .01). The difference in SBP change for dapagliflozin/exenatide versus placebo was -6.7 mm Hg. As expected, nausea and injection-site reactions were more frequent with dapagliflozin/exenatide than with placebo. Only two and three participants, respectively, discontinued because of adverse events. CONCLUSIONS: Compared with placebo, dapagliflozin/exenatide dual therapy reduced body weight, frequency of prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes. PMID- 27550387 TI - [Anticonvulsant add-on therapy with Eslicarbazepine acetate : Results of the EPOS study in adults in Germany]. AB - BACKGROUND: Due to inadequate seizure control achieved with antiepileptic drug (AED) monotherapy and the considerable side effects at high required doses, patients with partial-onset seizures (POS) often require AED combination therapy. Eslicarbazepine acetate (ESL) is licensed as an add-on therapy for POS and has a favorable tolerability profile. OBJECTIVES: To investigate retention, utilization, reported efficacy, safety and tolerability as well as effects on health-related quality of life using ESL as an add-on treatment to an established monotherapy in a real-world adult population with POS in Germany. PATIENTS AND METHODS: A subgroup analysis was performed on the data derived from the German study sites that had participated in an international, non-interventional, open label study conducted in eight European countries (eslicarbazepine acetate in partial-onset seizures, EPOS). Adult patients with POS whose physician had decided to prescribe add-on treatment with ESL to an established monotherapy were followed over a total period of approximately six months (three visits: baseline and after periods of approximately three and six months). Data collection included patient retention, reported efficacy, safety and tolerability as well as quality of life (QOLIE-10). RESULTS AND DISCUSSION: The subgroup analysis included 104 patients which had been enrolled at 38 German study sites. After 6 months, retention of ESL add-on therapy was 86.5 %, with 44.7 % of patients reporting seizure freedom over the 3 months prior to this visit. The overall tolerability of ESL add-on therapy was favorable: 32 adverse events (AE) were reported in 20 patients (19.2 %), while only two events in two patients were considered serious. No new safety signals were detected. PMID- 27550388 TI - [Specialist Training in Psychiatry and Psychotherapy : Evaluation of the East Westphalia-Lippe Academy curriculum]. AB - BACKGROUND: Despite of the undisputed impact of education quality on becoming a specialist in psychiatry and psychotherapist, systematic studies in this field do not exist in Germany, apart from the evaluation of practical education by the medical councils. MATERIALS AND METHODS: The Akademie-OWL, an education union of psychiatric clinics in the East Westphalia region of Germany, has provided 12 item questionnaire-based routine evaluations of theoretical education seminars since 2009. Seminars are held by consultants of psychiatry and psychotherapy within six separate weeks over a period of four years. All lecturers receive feedback from the evaluation. The results of this ongoing evaluation are presented using a typical example and in an aggregated format as a time series on the basis of one global item. RESULTS: The data show that (1) the full range of a five-point Likert scale is used by the candidates, (2) psychiatric competences of the lecturers are more positively evaluated than their didactic competences, (3) neither within the four-years period of psychiatric education nor between different generations of candidates are systematic changes of evaluation results observed, and (4) minor to moderate differences of evaluation were observed between the different thematic fields of psychiatry and psychotherapy. DISCUSSION: These results indicate the need of more systematic education research on establishing valid and reliable specific instruments as well as the need of systematic training of didactic competences of teaching consultants. PMID- 27550389 TI - Graphene-multiferroic interfaces for spintronics applications. AB - Graphene and magnetoelectric multiferroics are promising materials for spintronic devices with high performance and low energy consumption. A very long spin diffusion length and high carrier mobility make graphene attractive for spintronics. The coupling between ferroelectricity and magnetism, which characterises magnetoelectrics, opens the way towards unique device architectures. In this work, we combine the features of both materials by investigating the interface between graphene and BaMnO3, a magnetoelectric multiferroic. We show that electron charge is transferred across the interface and magnetization is induced in the graphene sheet due to the strong interaction between C and Mn. Depending on the relative orientation of graphene and BaMnO3, a quasi-half-metal or a magnetic semiconductor can be obtained. A remarkably large proximity induced spin splitting of the Dirac cones (~300 meV) is achieved. We also show how doping with acceptors can make the high-mobility region of the electronic bands experimentally accessible. This suggests a series of possible applications in spintronics (e.g. spin filters, spin injectors) for hybrid organic-multiferroic materials and reveals hybrid organic-multiferroics as a new class of materials that may exhibit exotic phenomena such as the quantum anomalous Hall effect and a Rashba spin-orbit induced topological gap. PMID- 27550390 TI - Drill-specific head impact exposure in youth football practice. AB - OBJECTIVE Although 70% of football players in the United States are youth players (6-14 years old), most research on head impacts in football has focused on high school, collegiate, or professional populations. The objective of this study was to identify the specific activities associated with high-magnitude (acceleration > 40g) head impacts in youth football practices. METHODS A total of 34 players (mean age 9.9 +/- 0.6 years) on 2 youth teams were equipped with helmet-mounted accelerometer arrays that recorded head accelerations associated with impacts in practices and games. Videos of practices and games were used to verify all head impacts and identify specific drills associated with each head impact. RESULTS A total of 6813 impacts were recorded, of which 408 had accelerations exceeding 40g (6.0%). For each type of practice drill, impact rates were computed that accounted for the length of time that teams spent on each drill. The tackling drill King of the Circle had the highest impact rate (95% CI 25.6-68.3 impacts/hr). Impact rates for tackling drills (those conducted without a blocker [95% CI 14.7-21.9 impacts/hr] and those with a blocker [95% CI 10.5-23.1 impacts/hr]) did not differ from game impact rates (95% CI 14.2-21.6 impacts/hr). Tackling drills were observed to have a greater proportion (between 40% and 50%) of impacts exceeding 60g than games (25%). The teams in this study participated in tackling or blocking drills for only 22% of their overall practice times, but these drills were responsible for 86% of all practice impacts exceeding 40g. CONCLUSIONS In youth football, high-magnitude impacts occur more often in practices than games, and some practice drills are associated with higher impact rates and accelerations than others. To mitigate high-magnitude head impact exposure in youth football, practices should be modified to decrease the time spent in drills with high impact rates, potentially eliminating a drill such as King of the Circle altogether. PMID- 27550392 TI - Use and Interpretation of Propensity Scores in Aging Research: A Guide for Clinical Researchers. AB - Observational studies are an important source of evidence for evaluating treatment benefits and harms in older adults, but lack of comparability in the outcome risk factors between the treatment groups leads to confounding. Propensity score (PS) analysis is widely used in aging research to reduce confounding. Understanding the assumptions and pitfalls of common PS analysis methods is fundamental to applying and interpreting PS analysis. This review was developed based on a symposium of the American Geriatrics Society Annual Meeting on the use and interpretation of PS analysis in May 2014. PS analysis involves two steps: estimation of PS and estimation of the treatment effect using PS. Typically estimated from a logistic model, PS reflects the probability of receiving a treatment given observed characteristics of an individual. PS can be viewed as a summary score that contains information on multiple confounders and is used in matching, weighting, or stratification to achieve confounder balance between the treatment groups to estimate the treatment effect. Of these methods, matching and weighting generally reduce confounding more effectively than stratification. Although PS is often included as a covariate in the outcome regression model, this is no longer a best practice because of its sensitivity to modeling assumption. None of these methods reduce confounding by unmeasured variables. The rationale, best practices, and caveats in conducting PS analysis are explained in this review using a case study that examined the effective of angiotensin-converting enzyme inhibitors on mortality and hospitalization in older adults with heart failure. PMID- 27550393 TI - El Nino and coral larval dispersal across the eastern Pacific marine barrier. AB - More than 5,000 km separates the frequently disturbed coral reefs of the Eastern Tropical Pacific (ETP) from western sources of population replenishment. It has been hypothesized that El Nino events facilitate eastward dispersal across this East Pacific Barrier (EPB). Here we present a biophysical coral larval dispersal model driven by 14.5 years of high-resolution surface ocean current data including the extreme 1997-1998 El Nino. We find no eastward cross-EPB connections over this period, which implies that ETP coral populations decimated by the 1998 bleaching event can only have recovered from eastern Pacific sources, in congruence with genetic data. Instead, rare connections between eastern and central Pacific reefs are simulated in a westward direction. Significant complexity and variability in the surface flows transporting larvae mean that generalized upper-ocean circulation patterns are poor descriptors of inter regional connectivity, complicating the assessment of how climate change will impact coral gene flow Pacific wide. PMID- 27550394 TI - Coral reef soundscapes may not be detectable far from the reef. AB - Biological sounds produced on coral reefs may provide settlement cues to marine larvae. Sound fields are composed of pressure and particle motion, which is the back and forth movement of acoustic particles. Particle motion (i.e., not pressure) is the relevant acoustic stimulus for many, if not most, marine animals. However, there have been no field measurements of reef particle motion. To address this deficiency, both pressure and particle motion were recorded at a range of distances from one Hawaiian coral reef at dawn and mid-morning on three separate days. Sound pressure attenuated with distance from the reef at dawn. Similar trends were apparent for particle velocity but with considerable variability. In general, average sound levels were low and perhaps too faint to be used as an orientation cue except very close to the reef. However, individual transient sounds that exceeded the mean values, sometimes by up to an order of magnitude, might be detectable far from the reef, depending on the hearing abilities of the larva. If sound is not being used as a long-range cue, it might still be useful for habitat selection or other biological activities within a reef. PMID- 27550395 TI - Brain metastasis features and association with tumor epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung. AB - AIM: Epidermal growth factor receptor (EGFR) mutations are frequent in pulmonary adenocarcinoma patients. The association between tumor EGFR mutation and characteristics of brain metastasis (BM) is still unclear. METHODS: We retrospectively reviewed pulmonary adenocarcinoma patients with and without BMs, and characteristics of BM to analyze the association between tumor EGFR mutation and characteristics of BM. RESULTS: Of 374 cases, 239 had EGFR mutations; 69 had BM at initial diagnosis, and 82 with BMs after treatment. All eligible patients received EGFR-tyrosine kinase inhibitors treatment. Older patients (>=70 years old) were less likely to have BMs than younger patients (25.8% vs 48%, P < 0.001). Patients with higher N stage had higher proportion of BMs (P = 0.006). Patients with exon 19 deletion were more likely to have BMs than those without EGFR mutation (48.1% vs 34.1%, P = 0.021). Patients with exon 19 deletion didn't have significantly higher chance of BMs at initial diagnosis but had higher chance to develop BM after treatment than those without EGFR mutation (35.6% vs 21.2%, P = 0.019). Patients with exon 19 deletion survived longer than those without EGFR mutation (1-year survival rate 95.8% vs 78.7%, P = 0.003). Thus, longer survival may lead to higher proportion of BM occurrence in patients with exon 19 deletion than those without EGFR mutation. CONCLUSIONS: In pulmonary adenocarcinoma, there is no significant difference in frequency of BMs at initial diagnosis between patients with EGFR mutation and wild type. However, after treatment, patients with EGFR mutations are significantly more likely to develop BM. PMID- 27550396 TI - Combined spectroscopies and molecular docking approach to characterizing the binding interaction of enalapril with bovine serum albumin. AB - The binding interaction between bovine serum albumin (BSA) and enalapril (ENPL) at the imitated physiological conditions (pH = 7.4) was investigated using UV-vis absorption spectroscopy (UV-vis), fluorescence emission spectroscopy (FES), synchronous fluorescence spectroscopy (SFS), Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD) and molecular docking methods. It can be deduced from the experimental results from the steady-state fluorescence spectroscopic titration that the intrinsic BSA fluorescence quenching mechanism induced by ENPL is static quenching, based on the decrease in the BSA quenching constants in the presence of ENPL with increase in temperature and BSA quenching rates >1010 L mol-1 sec-1 . This result indicates that the ENPL-BSA complex is formed through an intermolecular interaction of ENPL with BSA. The main bonding forces for interaction of BSA and ENPL are van der Waal's forces and hydrogen bonding interaction based on negative values of Gibbs free energy change (DeltaG0 ), enthalpic change (DeltaH0 ) and entropic change (DeltaS0 ). The binding of ENPL with BSA is an enthalpy-driven process due to |DeltaH degrees | > |TDeltaS degrees | in the binding process. The results of competitive binding experiments and molecular docking confirm that ENPL binds in BSA sub-domain IIA (site I) and results in a slight change in BSA conformation, but BSA still retains its alpha helical secondary structure. PMID- 27550397 TI - Secukinumab for the treatment of psoriatic arthritis. AB - INTRODUCTION: Secukinumab (Cosentyx) is an interleukin-17A (IL-17A) inhibitor administered subcutaneously. Through 2016, it had received approval in a number of countries, including the USA, Japan and in the EU for the treatment of plaque psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS). AREAS COVERED: This review addresses the mechanism of action, efficacy and safety of secukinumab observed in clinical studies of patients with PsA. Data from recent studies of secukinumab in psoriasis, PsA and AS are included. Expert commentary: Secukinumab appears to be effective in improving various aspects of PsA, including improvements in psoriatic skin, enthesitis and dactylitis, as well as inhibition of the radiographic progression of peripheral arthritis. Secukinumab was in general well tolerated; the most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection. PMID- 27550399 TI - Safety ad efficacy of direct oral anticoagulants for extended treatment of venous thromboembolism. AB - Currently available anticoagulants have limitations for long-term treatment of venous thromboembolism (VTE). We have evaluated the efficacy and safety of direct oral anticoagulants (DOACs) for extended treatment of VTE. Four randomized controlled trials (RCTs) comparing DOACs (apixaban, rivaroxaban, and dabigatran) with placebo or warfarin for extended treatment of VTE were published. Primary efficacy outcome was recurrent VTE or VTE-related death, and primary safety outcome was major bleeding. DOACs significantly lower the risk of recurrent VTE or VTE-related death compared to placebo/warfarin, as well as all-cause mortality. Risk of major bleeding is not different with DOACs compared to placebo/warfarin. However, DOACs are associated with a significantly higher rate of the composite of major and clinically relevant bleeding compared to placebo. In conclusion, DOACs are effective and safe for the extended treatment of VTE, and may reduce the risk of all-cause mortality. PMID- 27550400 TI - Low-Dose Quinidine Effectively Reduced Shocks in Brugada Syndrome Patients with an Implantable Cardioverter Defibrillator: A Chinese Case Series Report. AB - BACKGROUND: Only implantable cardioverter defibrillators (ICD) have been proven to prevent sudden cardiac death (SCD) in patients with Brugada syndrome (BrS). However, ICD discharge, whether appropriate or inappropriate, leads to impaired quality of life and even increases rehospitalization. Quinidine might prevent the recurrence of ventricular arrhythmia (VA); however, the effect of low-dose quinidine for preventing spontaneous arrhythmias remains less clear. METHODS: In our cardiology center, 10 confirmed patients with BrS (all men, mean age 38.7 +/- 6.72 years) who underwent appropriate ICD shocks due to recurrent VAs were treated with quinidine (<=200 mg/day) and followed regularly. RESULTS: All the patients underwent ICD shocks due to ventricular tachycardia (VT)/ventricular fibrillation (VF) before taking quinidine. A 24-hour distribution of VT/VF demonstrated that most of the events occurred in the sleeping time from 22:00 to 8:00. Quinidine prevented recurrence of VAs in nine patients. The other one patient took quinidine discontinuously because of anxiety suffered from less episodes of VA, and after psychological guidance, he took quinidine 200 mg/day and experienced no VA episodes from then on. In our series, only one patient suffered leukopenia related to quinidine. No other side effect was observed. CONCLUSIONS: Quinidine with a very low dose (<=200 mg/day) well controlled VT/VF recurrence for a long-term period in Chinese patients with BrS. Administration (at 21:00) according to the circadian distribution of VT/VF episodes might increase the efficiency and improve the patient's tolerance. PMID- 27550398 TI - Informed Family Member Involvement to Improve the Quality of Dementia Care in Nursing Homes. AB - OBJECTIVES: To describe the extent to which nursing homes engaged families in antipsychotic initiation decisions in the year before surveyor guidance revisions were implemented. DESIGN: Mixed-methods study based on semistructured interviews. SETTING: U.S. nursing homes (N = 20) from five CMS regions (III, IV, VI, VIII, IX). PARTICIPANTS: Family members of nursing home residents (N = 41). MEASUREMENTS: Family member responses to closed- and open-ended questions regarding involvement in resident care and antipsychotic initiation. Two researchers used a content analytical approach to code open responses to themes of family involvement in behavior management, decision-making, knowledge of risks and benefits, and informed consent. RESULTS: Fifty-four percent of family members felt highly involved in decisions about behavior management. Forty-two percent recalled being asked how to manage resident behavior without medication, and 17% recalled receipt of information about antipsychotic risks and benefits. Sixty-six percent felt highly involved in the process of initiating antipsychotic medication; 24% reported being asked for input into the antipsychotic initiation decision and knowing before the antipsychotic was started. CONCLUSION: Under existing federal regulations but before guidance revisions were implemented in 2013, more than 40% of families reported being involved in nonpharmacological behavior management of family members, but fewer than one in four reported being involved throughout the entire antipsychotic prescribing process. Interventions that standardize family engagement and promote adherence to existing federal regulations are needed. This discussion builds on these findings to weigh the policy options of greater enforcement of existing regulations versus enactment of new legislation to address this challenging issue. PMID- 27550401 TI - A prediction model of survival for patients with bone metastasis from uterine cervical cancer. AB - OBJECTIVE: The aim of the study was to establish a predictive model of survival period after bone metastasis from cervical cancer. METHODS: A total of 54 patients with bone metastasis from cervical cancer were included in the study. Data at the time of bone metastasis diagnosis, which included presence of extraskeletal metastasis, performance status, history of any previous radiation or chemotherapy, the number of bone metastases, onset period, and treatment were collected. Survival data were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: The median survival period after diagnosis of bone metastasis was 22 weeks (5 months). The 26- and 52-week survival rates after bone metastasis were 36.5% and 15.4%, respectively. Cox regression analysis showed that extraskeletal metastasis (hazard ratio [HR], 6.1; 95% CI, 2.2 to 16.6), performance status of 3 to 4 (HR, 7.8; 95% CI, 3.3 to 18.2), previous radiation or chemotherapy (HR, 3.3; 95% CI, 1.4 to 7.8), multiple bone metastases (HR, 1.9; 95% CI, 1.0 to 3.5), and a bone metastasis-free interval of <12 months (HR, 2.5; 95% CI, 1.2 to 5.3) were significantly and independently related to poor survival. A prognostic score was calculated by adding the number of each significant factor. The 26-week survival rates after diagnosis of bone metastasis were 70.1% in the group with a score <=2, 46.7% in the group with a score of 3, and 12.5% in the group with a score >=4 (p<0.001). CONCLUSION: This scoring system provided useful prognostic information on survival of patients with bone metastasis of cervical cancer. PMID- 27550402 TI - Can human papillomavirus (HPV) genotyping classify non-16/18 high-risk HPV infection by risk stratification? AB - OBJECTIVE: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV 45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. METHODS: The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. RESULTS: Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for >=cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (-) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV 39/51/56/59/66/68 (+). The age-adjusted odds ratios for >=CIN 2 of the HPV 31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (-) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). CONCLUSION: The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion. PMID- 27550403 TI - Groin lymph node detection and sentinel lymph node biopsy in vulvar cancer. AB - OBJECTIVE: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. METHODS: Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis. RESULTS: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028). CONCLUSION: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer. PMID- 27550404 TI - Clinical significance of radiotherapy in patients with primary uterine carcinosarcoma: a multicenter retrospective study (KROG 13-08). AB - OBJECTIVE: To investigate the role of radiotherapy (RT) in patients who underwent hysterectomy for uterine carcinosarcoma (UCS). METHODS: Patients with the International Federation of Gynecology and Obstetrics stage I-IVa UCS who were treated between 1990 and 2012 were identified retrospectively in a multi institutional database. Of 235 identified patients, 97 (41.3%) received adjuvant RT. Twenty-two patients with a history of previous pelvic RT were analyzed separately. Survival outcomes were assessed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Patients with a previous history of pelvic RT had poor survival outcomes, and 72.6% of these patients experienced locoregional recurrence; however, none received RT after a diagnosis of UCS. Univariate analyses revealed that pelvic lymphadenectomy (PLND) and para-aortic lymph node sampling were significant factors for locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS). Among patients without previous pelvic RT, the percentage of locoregional failure was lower for those who received adjuvant RT than for those who did not (28.5% vs. 17.5%, p=0.107). Multivariate analysis revealed significant correlations between PLND and LRRFS, distant metastasis-free survival, and DFS. In subgroup analyses, RT significantly improved the 5-year LRRFS rate of patients who did not undergo PLND (52.7% vs. 18.7% for non-RT, p<0.001). CONCLUSION: Adjuvant RT decreased the risk of locoregional recurrence after hysterectomy for UCS, particularly in patients without surgical nodal staging. Given the poorer locoregional outcomes of patients previously subjected to pelvic RT, meticulous re-administration of RT might improve locoregional control while leading to less toxicity in these patients. PMID- 27550405 TI - Carcinoma of the cervix in elderly patients treated with radiotherapy: patterns of care and treatment outcomes. AB - OBJECTIVE: The aim of this analysis was to examine the management of cervix cancer in elderly patients referred for radiotherapy and the results of treatment in terms of overall survival (OS), relapse-free survival (RFS), and treatment related toxicities. METHODS: Patients were eligible if they were aged >=75 years, newly diagnosed with cervix cancer and referred for radiotherapy as part of their treatment. Patient details were retrieved from the gynaecology service database where clinical, histopathological treatment and follow-up data were prospectively collected. RESULTS: From 1998 to 2010, 126 patients aged >=75 years, met selection criteria. Median age was 81.5 years. Eighty-one patients had definitive radiotherapy, 10 received adjuvant radiotherapy and 35 had palliative radiotherapy. Seventy-one percent of patients had the International Federation of Gynecology and Obstetrics stage 1b-2b disease. Median follow-up was 37 months. OS and RFS at 3 years among those treated with curative intent were 66.6% and 75.9% respectively with majority of patients dying without any evidence of cervix cancer. Grade 2 or more late toxicities were: bladder 5%, bowel 11%, and vagina 27%. Eastern Cooperative Oncology Group (ECOG) status was a significant predictor of OS and RFS with each unit increment in ECOG score increased the risk of death by 1.69 times (p<0.001). CONCLUSION: Following appropriate patient selection, elderly patients treated curatively with radiotherapy for cervix cancer have good disease control. Palliative hypofractionated regimens are well tolerated in patients unsuitable for radical treatment. PMID- 27550407 TI - Protective and therapeutic effects of metformin on gynecologic cancers. PMID- 27550406 TI - Surgical therapy of vulvar cancer: how to choose the correct reconstruction? AB - OBJECTIVE: To create a comprehensive algorithmic approach to reconstruction after vulvar cancer ablative surgery, which includes both traditional and perforator flaps, evaluating anatomical subunits and shape of the defect. METHODS: We retrospectively reviewed 80 cases of reconstruction after vulvar cancer ablative surgery, performed between June 2006 and January 2016, transferring 101 flaps. We registered the possibility to achieve the complete wound closure, even in presence of very complex defects, and the postoperative complications. On the basis of these experience, analyzing the choices made and considering the complications, we developed an algorithm to help with the selection of the flap in vulvoperineal reconstruction after oncologic ablative surgery for vulvar cancer. RESULTS: We employed eight types of different flaps, including 54 traditional fasciocutaneous V-Y flaps, 23 rectus abdominis myocutaneous flaps, 11 anterolateral thigh flaps, three V-Y gracilis myocutaneous flaps, three free style perforators V-Y flaps from the inner thigh, two Limberg flaps, two lotus flaps, two deep inferior epigastric artery perforator flap, and one superficial circumflex iliac artery perforator flap. The structures most frequently involved in resection were vulva, perineum, mons pubis, groins, vagina, urethra and, more rarely, rectum, bladder, and lower abdominal wall. CONCLUSION: The algorithm we implemented can be a useful tool to help flap selection. The key points in the decision-making process are: anatomical subunits to be covered, overall shape and symmetry of the defect and some patient features such as skin laxity or previous radiotherapy. Perforator flaps, when feasible, must be considered standard in vulvoperineal reconstruction, although in some cases traditional flaps remain the best choice. PMID- 27550409 TI - Exchange of Partial Liver Transplantation Between Children with Different Non Cirrhotic Metabolic Liver Diseases: How Do We Arrive There? AB - Hepatic-based metabolic disorders are characterized by an enzyme deficiency expressed solely or mainly in the liver. They are divided into cirrhotic or non cirrhotic metabolic liver diseases (NCMLDs), and most of them can be treated by liver transplantation. Because the livers with NCMLDs are usually structurally and functionally normal, the primary aim of the liver graft is to support the deficient enzymes rather than maintaining liver functions. Hence, we hypothesize that the exchange of partial liver grafts by the technique of auxiliary partial orthotopic liver transplantation (APOLT) between patients with 2 different NCMLDs may be feasible to replace the deficient enzymes in each patient. This hypothesis is based on the following conditions: (i) the patients have no chance of undergoing timely liver transplantation, (ii) the symptoms of each NCMLD may be alleviated after exchanging partial liver grafts, and (iii) each graft is anatomically appropriate for APOLT. In addition, we evaluate it with a focus on selection of cases, designing of graft sizes, and surgical techniques for reciprocal APOLT. PMID- 27550408 TI - Distal pancreatectomy with splenectomy for the management of splenic hilum metastasis in cytoreductive surgery of epithelial ovarian cancer. AB - OBJECTIVE: Distal pancreatectomy with splenectomy may be required for optimal cytoreductive surgery in patients with epithelial ovarian cancer (EOC) metastasized to splenic hilum. This study evaluates the morbidity and treatment outcomes of the uncommon procedure in the management of advanced or recurrent EOC. METHODS: This study recruited 18 patients who underwent distal pancreatectomy with splenectomy during cytoreductive surgery of EOC. Their clinicopathological characteristics and follow-up data were retrospectively analyzed. RESULTS: All tumors were confirmed as high-grade serous carcinomas. The median diameter of metastatic tumors located in splenic hilum was 3.5 cm (range, 1 to 10 cm). Optimal cytoreduction was achieved in all patients. Eight patients (44.4%) suffered from postoperative complications. The morbidity associated with distal pancreatectomy and splenectomy included pancreatic leakage (22.2%), encapsulated effusion in the left upper quadrant (11.1%), intra-abdominal infection (11.1%), pleural effusion with or without pulmonary atelectasis (11.1%), intestinal obstruction (5.6%), pneumonia (5.6%), postoperative hemorrhage (5.6%), and pancreatic pseudocyst (5.6%). There was no perioperative mortality. The majority of complications were treated successfully with conservative management. During the median follow-up duration of 25 months, nine patients experienced recurrence, and three patients died of the disease. The 2 year progression-free survival and overall survival were 40.2% and 84.8%, respectively. CONCLUSION: The inclusion of distal pancreatectomy with splenectomy as part of cytoreduction for the management of ovarian cancer was associated with high morbidity; however, the majority of complications could be managed with conservative therapy. PMID- 27550410 TI - Clinicians underwhelmed by "watered down" childhood obesity strategy. PMID- 27550411 TI - Europe importation of Panton-Valentine leukocidin-positive Staphylococcus aureus: a case report of recurrent furunculosis. PMID- 27550412 TI - Efficient unified rare variant association test by modeling the population genetic distribution in case-control studies. AB - Recent advancements in next-generation DNA sequencing technologies have made it plausible to study the association of rare variants with complex diseases. Due to the low frequency, rare variants need to be aggregated in association tests to achieve adequate power with reasonable sample sizes. Hierarchical modeling/kernel machine methods have gained popularity among many available methods for testing a set of rare variants collectively. Here, we propose a new score statistic based on a hierarchical model by additionally modeling the distribution of rare variants under the case-control study design. Results from extensive simulation studies show that the proposed method strikes a balance between robustness and power and outperforms several popular rare-variant association tests. We demonstrate the performance of our method using the Dallas Heart Study. PMID- 27550413 TI - Low-frequency bias tone suppression of auditory-nerve responses to low-level clicks and tones. AB - We used low-frequency "bias" tones (BT's) to explore whether click and tone responses are affected in the same way by cochlear active processes. In nonlinear systems the responses to clicks are not always simply related to the responses to tones. Cochlear amplifier gain depends on the incremental slope of the outer-hair cell (OHC) stereocilia mechano-electric transduction (MET) function. BTs transiently change the operating-point of OHC MET channels and can suppress cochlear-amplifier gain by pushing OHC METs into low-slope saturation regions. BT effects on single auditory-nerve (AN) fibers have been studied on tone responses but not on click responses. We recorded from AN fibers in anesthetized cats and compared tone and click responses using 50 Hz BTs at 70-120 dB SPL to manipulate OHC stereocilia position. BTs can also excite and thereby obscure the BT suppression. We measured AN-fiber response synchrony to BTs alone so that we could exclude suppression measurements when the BT synchrony might obscure the suppression. BT suppression of low-level tone and click responses followed the traditional pattern of twice-a-BT-cycle suppression with more suppression at one phase than the other. The major suppression phases of most fibers were tightly grouped with little difference between click and tone suppressions, which is consistent with low-level click and tone responses being amplified in the same way. The data are also consistent with the operating point of the OHC MET function varying smoothly from symmetric in the base to offset in the apex, and, in contrast, with the IHC MET function being offset throughout the cochlea. As previously reported, bias-tones presented alone excited AN fibers at one or more phases, a phenomena termed "peak splitting" with most BT excitation phases ~1/4 cycle before or after the major suppression phase. We explain peak splitting as being due to distortion in multiple fluid drives to inner-hair-cell stereocilia. PMID- 27550414 TI - The assessment of safe nursing care: development and psychometric evaluation. AB - AIM: To develop an instrument for the assessment of safe nursing care (ASNC) within the Iranian context and psychometrically evaluate its reliability and validity. BACKGROUND: There is a need for a valid and reliable instrument to assess how nurses employ the components of safe nursing care in clinical practice in non-Western countries. METHOD: This methodological study was conducted in two phases: (1) a qualitative phase of instrument development, and (2) a quantitative phase of psychometric evaluation of the assessment of safe nursing care (ASNC). The instrument's content validity was assessed by experts in the field of safe nursing care. The reliability of this instrument was examined using internal consistency reliability and intra-rater reliability analysis. Exploratory factor analysis was then conducted to establish the instrument's initial construct validity. RESULTS: The instrument developed was a questionnaire with 32 items. The Cronbach's alpha of the scale was 0.92, and Intra-class Correlation Coefficient for intra-rater reliability was 0.78. Exploratory factor analysis resulted in a four-factor solution: (1) evaluation of nursing skills, (2) assessing the patient's psychological needs, (3) assessing the patient's physical need, and (4) Assessing nurses' teamwork. The four factors accounted for 63.54% of the observed variance. CONCLUSION: The ASNC can be applied to a wide variety of settings because of the broad range of methods utilised to generate items and domains, its comprehensive consideration of the principles of safe care, and its initial reliability and validity. IMPLICATIONS FOR NURSING MANAGEMENT: The ASNC can help nurse managers assess whether clinical nurses are prepared to apply their safe care skills in clinical practice. It can also be used by clinical nurses to assess their own and peers' practice to detect potential areas for improvement in nursing care and help nurse managers with planning appropriate quality improvement programmes. PMID- 27550415 TI - Social risk, stigma and space: key concepts for understanding HIV vulnerability among black men who have sex with men in New York City. AB - Black men who have sex with men in the USA face disproportionate incidence rates of HIV. This paper presents findings from an ethnographic study conducted in New York City that explored the structural and socio-cultural factors shaping men's sexual relationships with the goal of furthering understandings of their HIV related vulnerability. Methods included participant observation and in-depth interviews with 31 Black men who have sex with men (three times each) and 17 key informants. We found that HIV vulnerability is perceived as produced through structural inequalities including economic insecurity, housing instability, and stigma and discrimination. The theoretical concepts of social risk, intersectional stigma, and the social production of space are offered as lenses through which to analyse how structural inequalities shape HIV vulnerability. We found that social risk shaped HIV vulnerability by influencing men's decisions in four domains: 1) where to find sexual partners, 2) where to engage in sexual relationships, 3) what kinds of relationships to seek, and 4) whether to carry and to use condoms. Advancing conceptualisations of social risk, we show that intersectional stigma and the social production of space are key processes through which social risk generates HIV vulnerability among Black men who have sex with men. PMID- 27550416 TI - Modulation of IL-6 induced RANKL expression in arthritic synovium by a transcription factor SOX5. AB - Receptor activator of nuclear factor kappaB ligand (RANKL) is critically involved in bone erosion of rheumatoid arthritis (RA). We previously reported association between younger age at onset of RA and a RANKL promoter SNP that conferred an elevated promoter activity via binding to a transcription factor SOX5. Here we study the regulation of SOX5 levels in relation to RANKL expression in RA synovial fibroblasts (SF) and the development of bone erosion in the collagen induced arthritis (CIA) mouse. Our data indicated SOX5 levels were higher in synovium and synovial fluid from RA compared to osteoarthritis patients. Pro inflammatory cytokines upregulated SOX5 and RANKL expression in both primary RA SF and the rheumatoid synovial fibroblast cell line, MH7A. Overexpression of SOX5 resulted in significantly increased RANKL levels, while knockdown of SOX5 resulted in diminished IL-6 mediated RANKL upregulation in MH7A cells. Chromatin immunoprecipitation (ChIP) showed approximately 3-fold enrichment of RANKL specific DNA in anti-SOX5 immunoprecipitate in IL-6 treated MH7A cells as compared to untreated cells. Locally silencing SOX5 gene significantly diminished RANKL positive cells and bone erosion in CIA mice. These findings suggest SOX5 is an important regulator of IL-6-induced RANKL expression in RA SF. PMID- 27550417 TI - Serum Galanin Levels in Young Healthy Lean and Obese Non-Diabetic Men during an Oral Glucose Tolerance Test. AB - Galanin (GAL) is a neuropeptide involved in the homeostasis of energy metabolism. The objective of this study was to investigate the serum levels of GAL during an oral glucose tolerance test (OGTT) in lean and obese young men. This cross sectional study included 30 obese non-diabetic young men (median 22 years; mean BMI 37 kg/m(2)) and 30 healthy lean men (median 23 years; mean BMI 22 kg/m(2)). Serum GAL was determined during OGTT. The results of this study include that serum GAL levels showed a reduction during OGTT compared with basal levels in the lean subjects group. Conversely, serum GAL levels increased significantly during OGTT in obese subjects. Serum GAL levels were also higher in obese non-diabetic men compared with lean subjects during fasting and in every period of the OGTT (p < 0.001). Serum GAL levels were positively correlated with BMI, total fat, visceral fat, HOMA-IR, total cholesterol, triglycerides and Leptin. A multiple regression analysis revealed that serum insulin levels at 30, 60 and 120 minutes during the OGTT is the most predictive variable for serum GAL levels (p < 0.001). In conclusion, serum GAL levels are significantly higher in the obese group compared with lean subjects during an OGTT. PMID- 27550418 TI - Comparative assessment of arabin pessary, cervical cerclage and medical management for preterm birth prevention in high-risk pregnancies. AB - OBJECTIVE: This study aimed to compare the efficacy of combined use of Arabin pessary, cervical cerclage and progesterone with progesterone-only management of pregnant women at high risk of preterm birth. MATERIALS AND METHODS: The study included 203 pregnant women at high risk of preterm birth who were randomised to receive Arabin pessary (Group 1, n = 82) and progesterone, circular cervical cerclage and progesterone (Group 2, n = 121) or progesterone treatment only (Group3, controls, n = 50). Patients in the pessary and cerclage group also received progesterone. RESULTS: The use of Arabin pessary combined with progesterone resulted in a 2.5-fold decrease in the rate of vaginal dysbiosis in pregnancy (p = 0.015) and almost three-fold reduction in in the postpartum period (p = 0.037), combined with circular cervical cerclage and progesterone. Suture eruption was observed in 4.3% of women. In patients with abnormal placental location, placental migration was observed in 62.1% of patients in Group I, 52.1% in Group II and a significantly lower proportion of patients (14.0%) in Group III (p = 0.001). Bleeding during pregnancy was observed significantly more often in both comparison groups (p = 0.005). Incidence of intrapartum bleeding was 17.4% (p = 0.011) in Group II and 24.5% in Group III (p = 0.002). Intrapartum chorioamnionitis was observed in 4.3% of patients in Group II and 2.04% of patients in Group III. CONCLUSIONS: The use of Arabin pessary compbined with progesterone reduces the rate of infectious complications and bleeding during pregnancy and the postpartum period. PMID- 27550419 TI - Actinoplanes subglobosus sp. nov., isolated from mixed deciduous forest soil. AB - A novel filamentous bacterial strain, A-T 5400T, which developed subglobose sporangia at the end of sporangiophores on substrate mycelia, was isolated from mixed deciduous forest soil collected in Thailand. The taxonomic position of this micro-organism was described using a polyphasic approach. The 16S rRNA gene sequence and phylogenetic analysis indicated that strain A-T 5400T belonged to the genus Actinoplanes and was most closely related to 'Actinoplanes hulinensis' NEAU-M9 (98.82 % 16S rRNA gene sequence similarity) and Actinoplanes philippinensis NBRC 13878T (98.75 %). The DNA-DNA relatedness values that distinguished the novel strain from the closest species were below 70 %. The cell wall peptidoglycan contained meso-diaminopimelic acid. The whole-cell sugars were ribose, galactose, glucose and xylose. The predominant menaquinone was MK-9(H4). The diagnostic phospholipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. The predominant cellular fatty acids were unsaturated fatty acids C16 : 1, branched fatty acids iso-C16 : 0 and iso-C15 : 0. The G+C content of the genomic DNA was 71 mol%. Following evidence from phenotypic, chemotaxonomic and genotypic studies, the new isolate is proposed to represent a novel species of the genus Actinoplanes named Actinoplanes subglobosus sp. nov. The type strain is A-T 5400T (=BCC 42734T=TBRC 5832T=NBRC 109645T). PMID- 27550421 TI - Synergistic Effects of Social Isolation and Morphine Addiction on Reduced Neurogenesis and BDNF Levels and the Resultant Deficits in Cognition and Emotional State in Male Rats. AB - INTRODUCTION: Addiction to drugs of abuse is a devastating condition which results in deterioration of brain function. On the other hand, social isolation also produces cognitive deficits such as learning and memory impairment. This study was designed to evaluate the potential negative synergistic effects of social isolation and morphine addiction on brain functions. METHODS AND MATERIAL: One hundred and two Sprague-Dawley rats were randomly divided into four groups for assessing neurogenesis and behaviour: group-housed, isolated, morphine treated group-housed and morphine-treated isolated groups. Morphine- treated animals received BrdU (50 mg/kg; i.p.) and Morphine (0.75 mg/rat; i.p.) for 14 consecutive days, whereas, control rats received BrdU (50 mg/kg; i.p.) only. At the end of the study, Morris water maze and elevated plus maze tasks were performed to assess spatial working memory and anxiety levels, respectively. Furthermore, neurogenesis and BDNF levels were studied. RESULTS: Reference and working memory was markedly impaired in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Neurogenesis and BDNF levels were reduced in isolated and morphine treated isolated rats as compared to group-housed rats and morphine-treated group housed rats, respectively. Furthermore, rats in both isolated groups demonstrated low anxiety levels when compared to group housed groups. CONCLUSION: Isolation during addiction imparts devastating effects on brain. Thus, socialization of addicts can minimize addiction - induce cognitive deficits and improve neurogenesis. PMID- 27550422 TI - A symmetry breaking phase transition-triggered high-temperature solid-state quadratic nonlinear optical switch coupled with a switchable dielectric constant in an organic-inorganic hybrid compound. AB - An organic-inorganic hybrid compound, [NH3(CH2)5NH3]SbCl5, exhibits a switchable second harmonic generation (SHG) effect between SHG-OFF and SHG-ON states and tunable dielectric behaviors between high and low dielectric states, connected with the changes in the dynamics of 1,5-pentanediammonium cations during its centrosymmetric-to-noncentrosymmetric symmetry breaking phase transition at 365.4 K. PMID- 27550420 TI - 18F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with 18F-FDG and 11C-Methionine PET. AB - PURPOSE: The purpose of this study was to evaluate the usefulness of L-4-borono-2 18F-fluoro-phenylalanine (18F-FBPA) as a tumor-specific probe, in comparison to 18F-FDG and 11C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. METHODS: Cellular analyses of FBPA were performed to evaluate the transportablity and Km value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K1, k2) and maximum standardized uptake value (SUVmax). RESULTS: The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The Km value of 18F-FBPA for LAT1 (196.8 +/- 11.4 MUM) was dramatically lower than that for LAT2 (2813.8 +/- 574.5 MUM), suggesting the higher selectivity of 18F-FBPA for LAT1. K1 and k2 values were significantly smaller in 18F-FBPA PET (K1 = 0.04 +/- 0.01 ml/ccm/min and k2 = 0.07 +/- 0.01 /min) as compared to 11C-Met PET (0.22 +/- 0.09 and 0.52 +/- 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of 18F-FDG in the tumor and inflammatory lesions (7.2 +/- 2.1 and 4.6 +/- 0.63, respectively) as compared to both 18F-FBPA (3.2 +/- 0.40 and 1.9 +/- 0.19) and 11C-Met (3.4 +/- 0.43 and 1.6 +/- 0.11). No significant difference was observed between 18F-FBPA and 11C-Met in the static PET images. CONCLUSION: This study shows the utility of 18F-FBPA as a tumor specific probe of LAT1 with low accumulation in the inflammatory lesions. PMID- 27550423 TI - Prognostic and predictive values of diffusion and perfusion MRI in paediatric intracranial ependymomas in a large national study. AB - OBJECTIVE: To assess the relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) derived, respectively, from perfusion and diffusion pre-operative MRI of intracranial ependymomas and their predictive and prognostic values. METHODS: Pre-operative MRI and clinical data for intracranial ependymomas diagnosed between January 2000 and December 2013 were retrospectively retrieved from a web-based national database. MRI data included diffusion (62 patients) and perfusion (20 patients) MRI. Patient age, histopathological diagnosis, tumour location, ADC, relative ADC (rADC) and rCBV were considered as potential factors in a survival analysis. Survival rates were estimated using the Kaplan-Meier method. Univariate analyses were performed using the log-rank test to compare groups. We also performed a multivariate analysis, applying the Cox proportional hazards model. RESULTS: ADC and rADC values within hypointense regions differed significantly between grades II and III (p = 0.01). The 75th percentile of ADC within hypointense regions and the 25th percentile of rCBV within non-enhancing lesions were prognostic of disease-free survival (p = 0.004, p = 0.05). A significant correlation was found between the 75th percentile of rCBV and the 25th percentile of rADC (p = 0.01) in enhancing regions of grade-III tumours. CONCLUSION: Pre-operative rADC and rCBV could be used as prognostic factors for clinical outcome and to predict histological grade in paediatric ependymomas. ADVANCES IN KNOWLEDGE: Prognostic value of diffusion and perfusion MRI in paediatric ependymoma was found and may play a role in the prognostic classification of patients in order to design more tailored treatment strategies. PMID- 27550424 TI - Mechanisms for dehydrogenation and hydrogenation of N-heterocycles using PNP pincer-supported iron catalysts: a density functional study. AB - The catalytic dehydrogenation and hydrogenation of N-heterocycles have potential applications in organic hydrogen storage. Recently, Fe(HPNP)(CO)(H)(HBH3) (cp1) and Fe(HPNP)(CO)(H)(Br) (cp2), the iron(ii) complexes supported by bis(phosphino)amine pincer (Fe-PNP) (PNP = N(CH2CH2P(i)Pr2)2), have been reported to be the starting complexes which can catalyze the dehydrogenation and hydrogenation of N-heterocycles. The active species were proposed to be the trans dihydride complexes, Fe(HPNP)(CO)(H)2 (cp4) and Fe(PNP)(CO)(H) (cp3), which can be interconverted. Here, our density functional study revealed that the N heterocyclic substrate plays a role in the formation of cp4 from cp1, while the tert-butoxide base assists with the formation of cp3 from cp2. The mechanism for cp3 catalyzed dehydrogenation of a 1,2,3,4-tetrahydroquinoline (THQ) substrate to quinoline (Q) involves two main steps: (i) dehydrogenation of THQ to 3,4 dihydroquinoline (34DHQ) and (ii) dehydrogenation of 34DHQ to Q. In each dehydrogenation step, the proton is transferred from the substrate to the N of the PNP ligand of cp3. An ion-pair complex between Fe-PNP and the deprotonated substrate is then formed before the hydride at the adjacent C is transferred to Fe. Notably, the isomerization of 34DHQ to 14DHQ or 12DHQ is not necessary, as the bifunctionality of Fe-PNP in cp3 can stabilize the ion-pair complex and facilitate direct dehydrogenation of the C3-C4 bond in 34DHQ. On the other hand, the mechanism for hydrogenation of Q involves the initial formation of 14DHQ, which can easily isomerize to 34DHQ with the assistance of a tert-butoxide base. Finally, 34DHQ is dehydrogenated to THQ. As the overall energy barriers for cp3 catalyzed dehydrogenation of THQ (+27.6 kcal mol(-1)) and cp4 catalyzed hydrogenation of Q (+23.8 kcal mol(-1)) are only slightly different, reaction conditions can be conveniently adjusted to favor either the dehydrogenation or hydrogenation process. Insights into the role of metal-ligand cooperativity in Fe PNP complexes in promoting the dehydrogenation and the hydrogenation of N heterocycles should benefit the development of efficient catalysts for organic hydrogen storage. PMID- 27550426 TI - The antidepressant effect of ketamine: Mediated by AMPA receptors? PMID- 27550425 TI - Trends in the epidemiology of cardiovascular disease in the UK. AB - Cardiovascular disease (CVD) mortality in the UK is declining; however, CVD burden comes not only from deaths, but also from those living with the disease. This review uses national datasets with multiple years of data to present secular trends in mortality, morbidity, and treatment for all CVD and specific subtypes within the UK. We produced all-ages and premature age-standardised mortality rates by gender, standardised to the 2013 European Standard Population, using data from the national statistics agencies of the UK. We obtained data on hospital admissions from the National Health Service records, using the main diagnosis. Prevalence data come from the Quality and Outcome Framework and national surveys. Total CVD mortality declined by 68% between 1980 and 2013 in the UK. Similar decreases were seen for coronary heart disease and stroke. Coronary heart disease prevalence has remained constant at around 3% in England and 4% in Scotland, Wales, and Northern Ireland. Hospital admissions for all CVD increased by over 46 000 between 2010/2011 and 2013/2014, with more than 36 500 of these increased admissions for men. Hospital admission trends vary by country and CVD condition. CVD prescriptions and operations have increased over the last decade. CVD mortality has declined notably for both men and women while hospital admissions have increased. CVD prevalence shows little evidence of change. This review highlights that improvements in the burden of CVD have not occurred equally between the four constituent countries of the UK, or between men and women. PMID- 27550427 TI - Fabrication of Long-Term Underwater Superoleophobic Al Surfaces and Application on Underwater Lossless Manipulation of Non-Polar Organic Liquids. AB - Underwater superoleophobic surfaces have different applications in fields from oil/water separation to underwater lossless manipulation. This kind of surfaces can be easily transformed from superhydrophilic surfaces in air, which means the stability of superhydrophilicity in air determines the stability of underwater superoleophobicity. However, superhydrophilic surfaces fabricated by some existing methods easily become hydrophobic or superhydrophobic in air with time. Here, a facile method combined with electrochemical etching and boiling water immersion is developed to fabricate long-term underwater superoleophobic surfaces. The surface morphologies and chemical compositions are investigated. The results show that the electrochemically etched and boiling-water immersed Al surfaces have excellent long-term superhydrophilicity in air for over 1 year and boehmite plays an important role in maintaining long-term stability of wettability. Based on the fabricated underwater superoleophobic surfaces, a special method and device were developed to realize the underwater lossless manipulation of immiscible organic liquid droplets with a large volume. The capture and release of liquid droplets were realized by controlling the resultant force of the applied driving pressure, gravity and buoyancy. The research has potential application in research-fields such as the transfer of valuable reagents, accurate control of miniature chemical reactions, droplet-based reactors, and eliminates contamination of manipulator components. PMID- 27550428 TI - Synthesis and Antimicrobial Evaluation of (Z)-5-((3-phenyl-1H-pyrazol-4- yl)methylene)-2-thioxothiazolidin-4-one Derivatives. AB - BACKGROUND: An alarming increment in pathogenic resistance to existing anti microbial agents is a serious problem and the treatment of these bacterial infections is becoming increasingly challenging. Therefore, there is an urgent need to develop novel antimicrobial agents. OBJECTIVE: As a part of our ongoing studies toward the development of novel antibacterial agents, the synthesis and antibacterial activity of a series of (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene) 2-thioxothiazolidin-4-one derivatives will be discussed in this study. METHOD: (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives were designed, synthesized and evaluated for antibacterial activity. The structures were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. All of the synthesized compounds were evaluated in vitro using a 96-well microtiter plate and a serial dilution method to obtain their minimum inhibitory concentration (MIC) values against a variety of different strains, including multidrug-resistant clinical isolates. RESULTS: The antibacterial test in-vitro showed that most compounds in series 7 and 9 exhibited significant inhibitory activities against anaerobic bacteria (Streptococcus mutans) strains with a MIC value of 1 ug/mL. Compounds 7c and 9c showed the most potent activity against MRSA (3167 and 3506) with a minimum inhibitory concentration (MIC) value of 1 ug/mL, which is equivalent to moxifloxacin and greater than gatifloxacin, oxacillin and norfloxacin. Additionally, compound 9c showed potent antibacterial activity against Bacillus subtilis (aerobic bacteria) with a MIC value of 2 ug/mL. CONCLUSION: The work suggests that these type of rhodanine compounds had a better potent activity against MRSA compared with other perviously reported rhodanine derivatives, which might provide a valuable information for the development of new antibacterial agents against multidrug-resistant clinical isolates MRSA. PMID- 27550429 TI - Effectiveness of timely intraoperative iodine irrigation during cataract surgery. AB - PURPOSE: To determine the antiseptic efficacy of timely intraoperative iodine irrigation during cataract surgery. METHODS: A total of 198 eyes of 99 cataract surgery patients were studied. The eyes were randomly assigned to treatment with or without timely intraoperative iodine irrigation of the surgical field with an iodine compound equivalent to 0.33 % povidone-iodine. In eyes in the timely intraoperative iodine irrigation group, the ocular surface was irrigated twice intraoperatively-before the initial incision and before insertion of the intraocular lens (IOL). The efficacy of the antiseptic treatment was evaluated by culture tests using scrapings of the surface of the sclerocornea and conjunctiva to the left of the incision and by broad-range real-time PCR for bacterial 16S ribosomal DNA using scrapings from the right side of the incision. RESULTS: Following intraoperative application of the iodine, bacteria were not detected in cultures of the samples. For the control eyes without timely iodine irrigation, cultures of samples from five and two eyes were positive before the initial incision and before IOL insertion, respectively. The bacterial DNA copy number before the initial incision was 1.7 +/- 0.5 * 103, which was significantly lower than that of the control eyes (1.7 +/- 0.6 * 104). For both groups of eyes, the bacterial DNA copy number was significantly lower before the IOL insertion depending on the time course. When the antiseptic effect of the iodine irrigation and time course on bacterial DNA copy number was analyzed using generalized mixed linear regression, both were found to be significantly effective. No significant intraoperative epithelial defect was observed. The postoperative corneal endothelial cell count did not differ significantly between the two groups of eyes. CONCLUSIONS: Timely iodine irrigation can serve as a simple and useful adjunctive disinfection step in cataract surgery. PMID- 27550430 TI - Erratum to: Spinal dumbbell lipoblastoma: a case-based update. PMID- 27550431 TI - Erratum to: Intracranial germ cell tumors: a multi-institutional experience from three tertiary care centers in India. PMID- 27550432 TI - Intracranial abscess as a complication of X-linked agammaglobulinemia. PMID- 27550433 TI - Open and endoscopic excision of calvarial dermoid and epidermoid cysts: a single center experience on 128 consecutive cases. AB - OBJECTIVE: Dermoid and epidermoid cysts rank among the most common pediatric tumors. We analyzed the outcomes of surgical excision of dermal and epidermal inclusion cysts in a large consecutive series of children. METHODS: We retrospectively reviewed 128 consecutive children who underwent calvarial inclusion cyst resection between 2000 and 2010 at NYU Langone Medical Center. Demographic information, neurological exam, lesion location, lesion diameter, type of treatment, extent of resection, time of follow-up, and recurrence were collected. RESULTS: The cohort includes 67 girls (52.3 %) and 61 boys (47.7 %). Age at diagnosis ranged from birth to 6.5 years (mean of 1.2 years) with surgical intervention between 1 month and 20 years of age (1.5 +/- 2.1). Of the 128 patients, 107 underwent open resection. Surgical approach was determined by the senior surgeon. Location, postoperative cosmesis, and family preference were the determining factors. Endoscopic resection was favored with supraorbital and glabellar lesions (75 % endoscopic versus 25 % open) using a rigid scope via a single incision. Erosion of the outer table and involvement of the inner table was noted in 20 patients (15 %), 14 of which were reconstructed using a split thickness calvarial graft. These lesions were noted to be significantly larger than lesions where cranioplasty was not used (1.9 +/- 2.81 cm versus 1.23 +/- 0.98 cm, p = 0.022). Gross total resection was achieved in all cases. DISCUSSION: Complete removal and cure from dermoid and epidermoid inclusion cysts are possible. Complications are few. Endoscopic approaches are useful to improve cosmesis and limit tissue damage for lesions near the orbits. PMID- 27550434 TI - Global Health's Grand Challenge: A Healthy Planet and Healthy People. PMID- 27550435 TI - MUW researcher of the month. PMID- 27550436 TI - Short-term effect of aflibercept on visual acuity and central macular thickness in patients not responding to ranibizumab and bevacizumab. AB - PURPOSE: To analyze the clinical outcome of treatment with aflibercept in patients not responding to ranibizumab and bevacizumab. METHODS: Retrospective review of 32 eyes from 30 consecutive patients with choroidal neovascularization (CNV) who showed no response to treatment with ranibizumab or bevacizumab and were switched to aflibercept. Visual acuity, central macular thickness (CMT) and presence or absence of intraretinal or subretinal fluid were analyzed before switching to aflibercept, after each of three uploading dose injections of aflibercept and 6, 8 and 10 weeks after the third aflibercept injection. All eyes had previous ranibizumab injections and the mean number of previous injections was 14.75 (+/- 7.38). Mean duration of previous anti-vascular endothelial growth factor (VEGF) treatment was 38 months (+/- 27.35 months). RESULTS: Mean visual acuity before switching to aflibercept was 0.40 +/- 0.30 logMAR. After the third injection visual acuity was 0.3 +/- 0.3 logMAR and 10 weeks after the third injection it was 0.50 +/- 0.20 logMAR. No significant differences were seen during treatment and follow-up. The mean CMT was 394 +/- 118 um at baseline, at follow-up (first, second and third, group week 6, group week 8 and group week 10) it was 317 +/- 108 um, 301 +/- 99 um, 292 +/- 83 um, 270 +/- 78 um, 340 +/- 146 um and 377 +/- 92 um, respectively. Significant reductions in CMT were seen between the first and third follow-up injections and at group week 8. Of the patients 59.4 % were complete non-responders to aflibercept. CONCLUSION: Aflibercept results in improvement in CMT in non-responders to ranibizumab and bevacizumab as long as therapy is given continuously and can therefore be an alternative therapy. PMID- 27550437 TI - Lipid composition in a strain of Bacillus subtilis, a producer of iturin A lipopeptides that are active against uropathogenic bacteria. AB - Urinary tract infections are a common disease in humans. Therefore, new methods are needed to destroy biofilms that are formed by uropathogens. Iturin A lipopeptides (LPs) C14 and C15 are potent biosurfactants synthetized by the Bacillus subtilis I'1a strain. The biological activity of extracted LPs was confirmed by examining extracts from I'1a cultures against uropathogenic bacteria that had been isolated from biofilms on urinary catheters. Compared with cultures of DSM 3257, which produce surfactin at a relatively low level, the extract obtained from strain I'1a exhibited a greater inhibitory effect against both planktonic and sessile forms of Escherichia coli, Serratia marcescens, Enterobacter cloacae, Proteus mirabilis, Citrobacter freundii and Enterococcus faecalis. Moreover, cyclic LP biosurfactants may disturb the integrity of cytoplasmic membranes; therefore, we investigated the effects of synthetized LPs on fatty acids and phospholipids of B. subtilis. LPs and lipids were analyzed using GC-MS, LC-MS/MS and MALDI-TOF/TOF techniques. Compared with B. subtilis DSM 3257, membranes of the I'1a strain were characterized by an increased amount of anteiso fatty acids and a ten-fold higher ratio of phosphatidylglycerol (PG)-to phosphatidylethanolamine (PE). Interestingly, in cultures of B. subtilis DSM 3257 supplemented with LP extracts of the I'1a strain, the PG-to-PE ratio was fourfold higher, and the amount of anteiso fatty acids was also increased. PMID- 27550438 TI - [The proportion of unaccompanied refugee minors suffering from psychiatric disorders in Germany]. AB - Objective: This article is the first investigation into the proportion of unaccompanied refugee minors suffering from psychiatric disorders in Germany. Method: In a retrospective study done between 2013 and 2015, any refugees showing symptoms of a psychiatric disorder during their stay in a residential refugee center were referred to an Outpatient Department of Child and Adolescent Psychiatry for diagnostic assessment. To this end, special consultation hours were arranged. Besides the diagnoses, the number of emergency consultations occurring before and after the implementation of the special consultation hours was recorded. Results: Of the 75 refugee minors (75 %) referred, 56 were suffering from a psychiatric disorder, with posttraumatic stress disorder and depression being the most common diagnoses. Following implementation of the consultation hours, the number of refugee patients initially admitted in the Child and Adolescent Psychiatry on an emergency basis fell. Conclusions: Unaccompanied refugee minors are a highly vulnerable group that poses great challenges to clinical care. The implementation of special consultation hours is a constructive option for meeting these challenges. In particular, this special offer enables improvement of crisis management in the case of emergency consultations. PMID- 27550440 TI - National ADR Monitoring System in China. AB - It has been more than 25 years since an adverse drug reaction (ADR) monitoring agency was first established in China. In the past few years, the National ADR Monitoring System (NADRMS) has developed rapidly in the country. However, this system has not been reviewed in detail in the literature. Our aim was to demonstrate how individual case safety reports (ICSRs) are reported and evaluated and how data quality control is achieved in China. We also aimed to discuss the present status and future of NADRMS. We reviewed the relevant regulations and literature around ADR reporting in China. ADR report collection tools in China have gone through three phases, namely paper-based reporting, software-based reporting using standalone computers, and online reporting. Nowadays the online reporting system plays an important role in China and the number of ADR reports has rapidly increased. NADRMS is similar to most of the ADR reporting systems around the world, but also has its own unique characteristics such as four levels of monitoring agencies. In summary, there is still a long way to go for China to establish a high-level ADR monitoring system to ensure drug safety. PMID- 27550439 TI - Chronic and acute risk assessment of human exposed to novaluron-bifenthrin mixture in cabbage. AB - Based on the dissipation and residual level in cabbage determined by gas chromatography coupled with an electron capture detector (GC-ECD), chronic and acute risk assessments of the novaluron and bifenthrin were investigated. At different spiked levels, mean recoveries were between 81 and 108 % with relative standard deviations (RSDs) from 1.1 to 6.8 %. The limit of quantification (LOQ) was 0.01 mg kg(-1), and good linearity with correlation coefficient (>0.9997) were obtained. The half-lives of novaluron and bifenthrin in cabbage were in the range of 3.2~10 days. Based on the consumption data in China, the risk quotients (RQs) of novaluron and bifenthrin were all below 100 %. The chronic and acute risk of novaluron in cabbage was relatively low, while bifenthrin exerts higher acute risk to humans than chronic risk. The obtained results indicated that the use of novaluron-bifenthrin mixture does not seem to pose any chronic or acute risk to humans even if cabbages are consumed at high application dosages and short preharvest interval (PHI). PMID- 27550443 TI - Recognition of wake-sleep stage 1 multichannel eeg patterns using spectral entropy features for drowsiness detection. AB - Electroencephalographic (EEG) activity recorded during the entire sleep cycle reflects various complex processes associated with brain and exhibits a high degree of irregularity through various stages of sleep. The identification of transition from wakefulness to stage1 sleep is a challenging area of research for the biomedical community. In this paper, spectral entropy (SE) is used as a complexity measure to quantify irregularities in awake and stage1 sleep of 8 channel sleep EEG data from the polysomnographic recordings of ten healthy subjects. The SE measures of awake and stage1 sleep EEG data are estimated for each second and applied to a multilayer perceptron feed forward neural network (MLP-FF). The network is trained using back propagation algorithm for recognizing these two patterns. Initially, the MLP network is trained and tested for randomly chosen subject-wise combined datasets I and II and then for the combined large dataset III. In all cases, 60 % of the entire dataset is used for training while 20 % is used for testing and 20 % for validation. Results indicate that the MLP neural network learns with maximum testing accuracy of 95.9 % for dataset II. In the case of combined large dataset, the network performs with a maximum accuracy of 99.2 % with 100 hidden neurons. Results show that in channels O1, O2, F3 and F4 (A1, A2 as reference), the mean of the spectral entropy value is higher in awake state than in stage1 sleep indicating that the EEG becomes more regular and rhythmic as the subject attains stage1 sleep from wakefulness. However, in C3 and C4 the mean values of SE values are not very much discriminative of both groups. This may prove to be a very effective indicator for scoring the first two stages of sleep EEG and may be used to detect the transition from wakefulness to stage1 sleep. PMID- 27550442 TI - Comparison of composite prostate radiotherapy plan doses with dependent and independent boost phases. AB - Prostate cases commonly consist of dual phase planning with a primary plan followed by a boost. Traditionally, the boost phase is planned independently from the primary plan with the risk of generating hot or cold spots in the composite plan. Alternatively, boost phase can be planned taking into account the primary dose. The aim of this study was to compare the composite plans from independently and dependently planned boosts using dosimetric and radiobiological metrics. Ten consecutive prostate patients previously treated at our institution were used to conduct this study on the RaystationTM 4.0 treatment planning system. For each patient, two composite plans were developed: a primary plan with an independently planned boost and a primary plan with a dependently planned boost phase. The primary plan was prescribed to 54 Gy in 30 fractions to the primary planning target volume (PTV1) which includes prostate and seminal vesicles, while the boost phases were prescribed to 24 Gy in 12 fractions to the boost planning target volume (PTV2) that targets only the prostate. PTV coverage, max dose, median dose, target conformity, dose homogeneity, dose to OARs, and probabilities of benefit, injury, and complication-free tumor control (P+) were compared. Statistical significance was tested using either a 2-tailed Student's t-test or Wilcoxon signed-rank test. Dosimetrically, the composite plan with dependent boost phase exhibited smaller hotspots, lower maximum dose to the target without any significant change to normal tissue dose. Radiobiologically, for all but one patient, the percent difference in the P+ values between the two methods was not significant. A large percent difference in P+ value could be attributed to an inferior primary plan. The benefits of considering the dose in primary plan while planning the boost is not significant unless a poor primary plan was achieved. PMID- 27550441 TI - Prostheses size dependency of the mechanical response of the herniated human abdomen. AB - BACKGROUND: Hernia repairs still exhibit clinical complications, i.e. recurrence, discomfort and pain and mesh features are thought to be highly influent. The aim of this study is to evaluate the impact of the defect size and mesh type in an herniated abdominal wall using numerical models. METHODS: To do so, we have started from a FE model based on a real human abdomen geometry obtained by MRI, where we have provoked an incisional hernia of three different sizes. The surgical procedure was simulated by covering the hernia with a prostheses, and three surgical meshes with distinct mechanical properties were used for the hernia repair: an isotropic heavy-weight mesh (Surgipro @), a slightly anisotropic light-weight mesh (Optilene @) and a highly anisotropic medium-weight mesh (Infinit @). The mechanical response of the wall to a high intraabdominal pressure (corresponding to a coughing motion) was analyzed here. RESULTS: Our findings suggest that the anisotropy of the mesh becomes more relevant with the increase of the defect size. Additionally, according to our results Optilene @ showed the closest deformation to the natural distensibility of the abdomen while Infinit @ should be carefully used due to its excessive compliance. PMID- 27550444 TI - Mothering, Guiding, and Responding to Children: A Comparison of Women Abused and Not Abused by Intimate Partners. AB - Intimate partner violence (IPV) has many negative outcomes for women, children, and families. However, researchers have opposing perspectives and findings with respect to the effects on mothering for abused women. The assumption by some service providers that abused mothers are compromised in their parenting generally ignores the larger issue of male violence and women's and children's safety. The question examined in this study was whether there were differences in reported positive parenting responses with children between women who have experienced IPV and those who have not experienced IPV. The sample consisted of 1,211 mothers and came from two studies: The National Longitudinal Survey of Children and Youth, and The Healing Journey: A Longitudinal Study of Mothers Affected by Intimate Partner Violence. The Positive Interaction and Rational Parenting scales, adapted from Strayhorn and Weidman's Parenting Practices Scale, were used to measure parenting interactions. Bivariate correlations between the outcome variables and maternal age, maternal education, child age, and child sex were calculated to determine whether any of these variables were significantly related to the Positive Interaction Scale or Rational Parenting Scale. This was followed by ANCOVA to determine whether mothers who had experienced IPV differed in their scores on the two parenting scales from mothers who had not experienced IPV. Findings did not support the notion that abused women are compromised in their parenting responses with their children in regard to positive interactions and behavior management. Recommendations include a greater focus on the prevention of IPV, addressing the source of violence and providing appropriate support for mothers who experience IPV. PMID- 27550445 TI - eComment. Aneurysms of the pulmonary artery. PMID- 27550446 TI - eComment. The ways to increase the effectivity of pleurodesis. PMID- 27550448 TI - The Greater Genomic Landscape: The Heterogeneous Evolution of Cancer. AB - Results have historically shown a broad plasticity in the origin of tumors and their functions, with significant heterogeneity observed in both morphologies and functional capabilities. Largely unknown, however, are the mechanisms by which these variations occur and how these events influence tumor formation and behavior. Contemporary views on the origin of tumors focus mainly on the role of particular sets of driver transformations, mutational or epigenetic, with the occurrence of the observed heterogeneity as an accidental byproduct of oncogenesis. As such, we present a hypothesis that tumors form due to heterogeneous adaptive selection in response to environmental stress through intrinsic genomic sampling mechanisms. Specifically, we propose that eukaryotic cells intrinsically explore their available genomic information, the greater genomic landscape (GGL), in response to stress under normal conditions, long before the formation of a cancerous lesion. Finally, considering the influence of chromatin heterogeneity on the GGL, we propose a new class of compounds, chromatin-protective therapies (CPT), which target the physical variations in chromatin topology. In this approach, CPTs reduce the overall information space available to limit the formation of tumors or the development of drug-resistant phenotypes. Cancer Res; 76(19); 5605-9. (c)2016 AACR. PMID- 27550449 TI - Interleukin-30 Promotes Breast Cancer Growth and Progression. AB - The inflammatory tissue microenvironment that promotes the development of breast cancer is not fully understood. Here we report a role for elevated IL30 in supporting the breast cancer cell viability and invasive migration. IL30 was absent in normal mammary ducts, ductules, and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, IL30 was expressed frequently in breast cancer specimens where it was associated with triple-negative and HER2+ molecular subtypes. In stromal leukocytes found in primary tumors or tumor-draining lymph nodes, which included mainly CD14+ monocytes, CD68+ macrophages, and CD33+/CD11b+ myeloid cells, IL30 levels increased with disease stage and correlated with recurrence. A negative correlation was determined between IL30 expression by nodal stromal leukocytes and overall survival. In vitro studies showed that human recombinant IL30 upregulated expression of a pro-oncogenic program, including especially IL6 in both triple-negative and HER2+ breast cancer cells. In triple-negative breast cancer cells, IL30 boosted a broader program of proliferation, invasive migration, and an inflammatory milieu associated with KISS1-dependent metastasis. Silencing of STAT1/STAT3 signaling hindered the regulation of the primary growth and progression factors in breast cancer cells. IL30 administration in vivo fostered the growth of triple-negative breast cancer by promoting proliferation and vascular dissemination of cancer cells and the accumulation of intratumoral CD11b+/Gr1+ myeloid cell infiltrates. Overall, our results show how IL30 regulates breast cancer cell viability, migration, and gene expression to promote breast cancer growth and progression and its impact on patient outcome. Cancer Res; 76(21); 6218-29. (c)2016 AACR. PMID- 27550450 TI - Antitumor Properties of an IgG2-Enhanced Next-Generation MET Monoclonal Antibody That Degrades Wild-Type and Mutant MET Receptors. AB - A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14-mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb) that block MET-dependent signaling and tumor growth. In particular, the MET mAb KTN0073 and KTN0074 bind the Sema/PSI domain, at overlapping but distinct epitopes, preventing HGF interaction with MET and triggering receptor ubiquitination and degradation. Notably, both mAbs also triggered degradation of oncogenic MET exon 14 mutants, which propagate more durable MET signals due to a defect in receptor degradation. Mechanistic investigations showed that both mAbs engaged a pathway distinct from HGF-induced receptor degradation and protease mediated shedding, independently of signaling driven by the exon 14-encoded sequences in the intracellular juxtamembrane region of the MET receptor. Grafting the mAb variable regions onto the IgG2 constant region dramatically enhanced the tumor inhibitory activities of KTN0073 but not KTN0074, suggesting a specific influence of antibody isotype of the epitopes for these two MET mAbs. Overall, our results highlight KTN0073 as a novel IgG2-based MET mAb that acts through exon 14-independent mechanisms to degrade the MET receptor, potentially offering a therapeutic tool to treat a broader range of human tumors where MET is exon 14 mutated or amplified. Cancer Res; 76(19); 5788-97. (c)2016 AACR. PMID- 27550451 TI - Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells. AB - The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. (c)2016 AACR. PMID- 27550452 TI - Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming. AB - Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments. Moreover, the integrities of BATF-3-dependent dendritic cells specialized in crosspresentation/crosspriming of antigens to CD8+ T cells and of the type I IFN system were absolute requirements for the antitumor effects to occur. The irradiation regimen induced immune infiltrate changes in the irradiated and nonirradiated lesions featured by reductions in the total content of effector T cells, Tregs, and myeloid-derived suppressor cells, while effector T cells expressed more intracellular IFNgamma in both the irradiated and contralateral tumors. Importantly, 48 hours after irradiation, CD8+ TILs showed brighter expression of CD137 and PD1, thereby displaying more target molecules for the corresponding mAbs. Likewise, PD1 and CD137 were induced on tumor-infiltrating lymphocytes from surgically excised human carcinomas that were irradiated ex vivo These mechanisms involving crosspriming and CD8 T cells advocate clinical development of immunotherapy combinations with anti-PD1 plus anti-CD137 mAbs that can be synergistically accompanied by radiotherapy strategies, even if the disease is left outside the field of irradiation. Cancer Res; 76(20); 5994-6005. (c)2016 AACR. PMID- 27550453 TI - WWOX and p53 Dysregulation Synergize to Drive the Development of Osteosarcoma. AB - Osteosarcoma is a highly metastatic form of bone cancer in adolescents and young adults that is resistant to existing treatments. Development of an effective therapy has been hindered by very limited understanding of the mechanisms of osteosarcomagenesis. Here, we used genetically engineered mice to investigate the effects of deleting the tumor suppressor Wwox selectively in either osteoblast progenitors or mature osteoblasts. Mice with conditional deletion of Wwox in preosteoblasts (WwoxDeltaosx1) displayed a severe inhibition of osteogenesis accompanied by p53 upregulation, effects that were not observed in mice lacking Wwox in mature osteoblasts. Deletion of p53 in WwoxDeltaosx1 mice rescued the osteogenic defect. In addition, the Wwox;p53Deltaosx1 double knockout mice developed poorly differentiated osteosarcomas that resemble human osteosarcoma in histology, location, metastatic behavior, and gene expression. Strikingly, the development of osteosarcomas in these mice was greatly accelerated compared with mice lacking p53 only. In contrast, combined WWOX and p53 inactivation in mature osteoblasts did not accelerate osteosarcomagenesis compared with p53 inactivation alone. These findings provide evidence that a WWOX-p53 network regulates normal bone formation and that disruption of this network in osteoprogenitors results in accelerated osteosarcoma. The Wwox;p53Deltaosx1 double knockout establishes a new osteosarcoma model with significant advancement over existing models. Cancer Res; 76(20); 6107-17. (c)2016 AACR. PMID- 27550456 TI - [Philosophy of psychiatry]. PMID- 27550454 TI - INT6/EIF3E Controls the RNF8-Dependent Ubiquitylation Pathway and Facilitates DNA Double-Strand Break Repair in Human Cells. AB - Unrepaired DNA double-strand breaks (DSB) are the most destructive chromosomal lesions driving genomic instability, a core hallmark of cancer. Here, we identify the antioncogenic breast cancer factor INT6/EIF3E as an essential regulator of DSB repair that promotes homologous recombination (HR)-mediated repair and, to a lesser extent, nonhomologous end-joining repair. INT6 silencing impaired the accrual of the ubiquitin ligase RNF8 at DSBs and the formation of ubiquitin conjugates at DSB sites, especially Lys63-linked polyubiquitin chains, resulting in impaired recruitment of BRCA1, BRCA2, and RAD51, which are all involved in HR repair. In contrast, INT6 deficiency did not affect the accumulation of RNF168, 53BP1, or RPA at DSBs. In INT6-silenced cells, there was also an alteration in DNA damage-induced localization of MDC1, a key target for ATM phosphorylation, which is a prerequisite for RNF8 recruitment. The attenuated DNA damage localization of RNF8 resulting from INT6 depletion could be attributed to the defective retention of ATM previously reported by us. Our findings deepen insights into how INT6 protects against breast cancer by showing how it functions in DSB repair, with potential clinical implications for cancer therapy. Cancer Res; 76(20); 6054-65. (c)2016 AACR. PMID- 27550455 TI - The PARP Inhibitor AZD2461 Provides Insights into the Role of PARP3 Inhibition for Both Synthetic Lethality and Tolerability with Chemotherapy in Preclinical Models. AB - The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1 deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein, so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3 active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability. Cancer Res; 76(20); 6084-94. (c)2016 AACR. PMID- 27550457 TI - [Philosophy against psychiatry, right up against it]. AB - Since the early 1990s, there has been a tremendous new interest at the international level for researches at the crossroad between philosophy and psychiatry. This interest has been supported and quite stimulated by the foundation of a dedicated association, as well as by the establishment of a journal and the promotion of a new collection. My aim in this paper is to trace the origins of the so-called "new philosophy of psychiatry" field and to reconstruct its global intellectual dynamics during the past two decades. I try to identify, through the big diversity of the individual contributions, its dominant theoretical orientations but also what may appear as some of its philosophical blind spots. PMID- 27550458 TI - [On Michel Foucault's unpublished lectures on Ludwig Binswanger's existential analysis (Lille 1953-54)]. AB - This paper aims to analyze Michel Foucault's position toward phenomenological psychology and psychopathology during the 1950s, in light of the new documentary sources available today. Our investigation is especially focused on one of the courses given by Foucault at the University of Lille between 1952 and 1954, namely, the course on "Binswanger and phenomenology" (1953-54). The analysis of this course, which was conceived by Foucault within the context of a philosophical reflection on the anthropological problem of psychopathology, will finally allow us to re-ascribe Foucault the place he deserves in the field of "philosophy of psychiatry". PMID- 27550459 TI - [Philosophy of psychiatry and phenomenology of everyday life: The disruptions of ordinary experience in schizophrenia]. AB - The paper considers the philosophy of psychiatry from the perspective of everyday life, as a particular structure of experience. We outline some questions raised by disturbances typical of psychotic disorders with regard to a phenomenology of the everyday and common sense. As a link between philosophy and clinical psychopathology, this phenomenology implies a transcendental point of view, embedded in concrete and practical forms of ordinary experience, along with social norms. This opens the possibility of a mutual questioning between philosophy and psychiatry, drawing on its clinical, epistemological, and ethical dimensions. PMID- 27550460 TI - [Natural or interactive kinds? The transient mental disorders in Ian Hacking's lectures at the College de France (2000-2006)]. AB - The concepts developed by Ian Hacking during his lectures at the College de France (2000-2006) have provided an important contribution to the debates within the field of philosophy of psychiatry. Professor at the Chair of Philosophy and History of Scientific Concepts after Michel Foucault, Hacking is the author of a reflection on the classification of mental disorders, which arises from the problem of the natural kinds. In order to explain the case studies developed in Hacking's Paris lectures, we first go back to the definition of a series of concepts, then we discuss the status of his scientific metaphors. Finally we analyze the relationship between the notions, respectively, of "transient mental illness" and "culture-bound syndrome". We emphasize that the latter derives from the Canadian transcultural psychiatry. PMID- 27550462 TI - [Not Available]. PMID- 27550464 TI - [Not Available]. PMID- 27550461 TI - [The Research Domain Criteria (Rdoc), reductionism and clinical psychiatry]. AB - The focus of the advocates of the Research Domain Critria (RDoC) on faulty brain circuits has led some to suspect it of being a reductionist enterprise. And because RDoC will eventually impact clinical psychiatry, some have feared that it will transform clinical psychiatry in a mindless and applied neurobehavioral science. We argue that if RDoC is officially endorsing a kind of reductionism, the particular kind of reductionism it endorses is not suffering from the shortcomings of more classical forms of reductionism. Because of that, at least in principle, RDoC could enrich rather than impoverish clinical psychiatry. This paper raises few potential problems of the RDoC for clinical psychiatry caused by its implicit epistemological reductionism. PMID- 27550463 TI - [Where is going philosophy of psychiatry ?]. AB - This contribution provides a critical outline of the current trends in the field of "philosophy of psychiatry" by following their developments in the last decade. The first part of the paper focuses on the evolution of this field from a strictly conceptual approach to a perspective more attentive to the social, practical, and clinical dimension of psychiatry. The second part of the paper points out that the need of a mutual commitment of philosophy and psychiatry is perceived according to different ways by the countries involved in this research area. The paper deals especially with the case of France, where the enthusiasm for the "new philosophy of psychiatry" has not had the same impact on the philosophical scene as in the English speaking countries. In conclusion, the paper shows that the field of philosophy of psychiatry stands as a fertile ground for new forms of interaction between the analytic, and the continental philosophical traditions. This interaction takes place, more particularly, as regards such topics as normativity, language, and interpretation. PMID- 27550467 TI - Knowledge and Awareness of Sickle Cell Trait Among Young African American Adults. AB - Sickle cell trait (SCT) places individuals at risk of passing an abnormal hemoglobin gene to biological children and is associated with rare but serious complications. The present study sought to examine knowledge of SCT and awareness of personal trait status among 258 young African American adults. Participants were surveyed regarding demographics, medical history, and sources of sickle cell information before completing a trait knowledge questionnaire. Overall, participants possessed significant misinformation about the condition. Women and those who had learned about sickle cell from families displayed higher levels of knowledge. Most participants were uncertain of personal trait status, and many did not wish to be informed of it. Health care providers should be alert that individuals with SCT may be unaware of their condition and potential reproductive and health implications. Screening and reporting procedures should be examined to ensure individuals have access to and control of this vital health information. PMID- 27550466 TI - [Memory in disciplinary cultures and "sites" of memory in medicine : Maximilian Nitze (1848-1906) and the establishment of urology]. AB - The canon of material and immaterial references of the urological heritage must always be recognized as a part of a continous process of negotiation. Within German Urology the culture of remembrance on Maximilian Nitze reveals one of such processes. PMID- 27550468 TI - Cardiorespiratory Fitness, Adiposity, and Cardiometabolic Risk Factors in Schoolchildren: The FUPRECOL Study. AB - The aim of this study was to investigate the association between cardiorespiratory fitness (CRF) and cardiovascular risk factors (CVRF) in schoolchildren. A secondary aim was to evaluate the degree of association between overall and abdominal adiposity and CRF in a total of 1,875 children and adolescents attending public schools. We expressed CRF performance as the nearest stage (minute) completed and the estimated peak oxygen consumption. A CVRF ( Z score) was calculated and participants were divided into tertiles according to low and high levels of overall (sum of the skinfold thicknesses) and abdominal adiposity. Schoolchildren with a high-level of overall adiposity demonstrated significant differences in seven of the 10 variables analyzed (i.e., systolic and diastolic blood pressure, triglycerides, triglycerides/high density lipoproteins [HDL-c] ratio, total cholesterol, glucose, C-reactive protein [usCRP], HDL-c, low density lipoproteins [LDL-c], and cardiovascular risk score). Schoolchildren with high levels of both overall and abdominal adiposity and low CRF had the least favorable CVRF score. PMID- 27550470 TI - I'm Not Sure I Follow You Doctor .... PMID- 27550471 TI - Charge Spreading in Deep Eutectic Solvents. AB - Ab initio molecular dynamic simulations reveal significantly reduced ion charges in several choline-based deep eutectic solvents, which are cheap and eco-friendly alternatives to ionic liquids. Increasing hydrogen bond strength between the anion and the organic compound enhances charge spreading from the anion to the organic compound while the positive charge is stronger located at the cation. Nonetheless, the negative charge transferred from chloride to urea in choline chloride urea mixtures is negligible. Thus, it seems questionable if charge delocalization occurring through hydrogen bonding between the halide anion and the organic compound is responsible for the deep eutectic melting point. PMID- 27550469 TI - The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis. AB - Renal tubulointerstitial fibrosis (TIF) is the final pathway of various renal injuries that result in chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the regulation of cell proliferation, cell death, tissue regeneration, and tumorigenesis. Here, we report that the Hippo-Salvador pathway plays a role in disease development in patients with TIF and in a mouse model of TIF. Mice with tubular epithelial cell (TEC)-specific deletions of Sav1 (Salvador homolog 1) exhibited aggravated renal TIF, enhanced epithelial-mesenchymal transition-like phenotypic changes, apoptosis, and proliferation after unilateral ureteral obstruction (UUO). Moreover, Sav1 depletion in TECs increased transforming growth factor (TGF)-beta and activated beta-catenin expression after UUO, which likely accounts for the abovementioned enhanced TEC fibrotic phenotype. In addition, TAZ (transcriptional coactivator with PDZ-binding motif), a major downstream effector of the Hippo pathway, was significantly activated in Sav1-knockout mice in vivo. An in vitro study showed that TAZ directly regulates TGF-beta and TGF-beta receptor II expression. Collectively, our data indicate that the Hippo-Salvador pathway plays a role in the pathogenesis of TIF and that regulating this pathway may be a therapeutic strategy for reducing TIF. PMID- 27550472 TI - Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation. AB - Cisplatin (CP) is one of the most effective chemotherapeutic agents. Unfortunately, CP-induced nephrotoxicity hampered its use. This study aims to investigate the effect of vitamin E (Vit E) on CP-induced nephrotoxicity. Male white albino rats were divided to four group's six rats each and received either, 1% tween 80 in normal saline or Vit E (75 mg/kg) per day for 14 consecutive days or a single injection of CP (6 mg/kg) alone or CP (6 mg/kg) together with Vit E (75 mg/kg per day for 14 consecutive days). Five days after the CP injection, rats were euthanized; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly increased serum levels of creatinine and urea. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CP treatment. Vit E successfully lowered serum levels of urea and creatinine, enhanced creatinine clearance and diuresis, and normalized relative kidney/body weight. Furthermore, Vit E successfully normalized renal MDA and nitrite concentrations, elevated GSH level, and restored CAT and SOD activities in renal tissues. Histopathological examination of rat kidney revealed that Vit E significantly mitigated CP-induced renal damage. Importantly, administration of Vit E reduced kidney total platinum concentration indicating a role of platinum renal accumulation on the ability of Vit E to protect against CP nephrotoxicity. PMID- 27550473 TI - Fast determination of anthocyanins and free pelargonidin in fruits, fruit juices, and fruit wines by high-performance liquid chromatography using a core-shell column. AB - Anthocyanins are water-soluble pigments that are liable for colors ranging from red to blue of most fruits, vegetables, and flowers. A novel and fast method was developed for the determination of five anthocyanins and free pelargonidin by high-performance liquid chromatography coupled to photodiode array detection. A 10% formic acid and acetonitrile mixture was employed as mobile phase in the gradient elution mode. Mobile phase composition, column temperature, flow rate, injection volume, and column conditioning time were optimized by employing a stepwise strategy. Using a C18 core-shell column (100 * 4.6 mm, 2.7 MUm), the separation of six analytes was accomplished in less than 9.5 min with a run-to run analysis time of 19 min. The developed method was validated with respect to linearity (r > 0.9999), limit of detection, limit of quantification, intra /interday precision (<2%), accuracy (98.6-104.4%), and specificity. Afterwards, the method was applied to the determination of anthocyanins present in 15 different samples including fruits, fruit juices, and fruit wines. PMID- 27550474 TI - Launching a New Section 'Biomedical Engineering'. PMID- 27550475 TI - How to Act When Research Misconduct Is Not Detected by Software but Revealed by the Author of the Plagiarized Article. AB - The detection of plagiarism in scholarly articles is a complex process. It requires not just quantitative analysis with the similarity recording by anti plagiarism software but also assessment of the readers' opinion, pointing to the theft of ideas, methodologies, and graphics. In this article we describe a blatant case of plagiarism by Chinese authors, who copied a Russian article from a non-indexed and not widely visible Russian journal, and published their own report in English in an open-access journal indexed by Scopus and Web of Science and archived in PubMed Central. The details of copying in the translated English article were presented by the Russian author to the chief editor of the index journal, consultants from Scopus, anti-plagiarism experts, and the administrator of the Committee on Publication Ethics (COPE). The correspondents from Scopus and COPE pointed to the decisive role of the editors' of the English journal who may consider further actions if plagiarism is confirmed. After all, the chief editor of the English journal retracted the article on grounds of plagiarism and published a retraction note, although no details of the complexity of the case were reported. The case points to the need for combining anti-plagiarism efforts and actively seeking opinion of non-native English-speaking authors and readers who may spot intellectual theft which is not always detected by software. PMID- 27550476 TI - Dangerous Predatory Publishers Threaten Medical Research. AB - This article introduces predatory publishers in the context of biomedical sciences research. It describes the characteristics of predatory publishers, including spamming and using fake metrics, and it describes the problems they cause for science and universities. Predatory journals often fail to properly manage peer review, allowing pseudo-science to be published dressed up as authentic science. Academic evaluation is also affected, as some researchers take advantage of the quick, easy, and cheap publishing predatory journals provide. By understanding how predatory publishers operate, researchers can avoid becoming victimized by them. PMID- 27550477 TI - Peeled and Piled Volume Models of the Kidney that Show Actual Morphology. PMID- 27550479 TI - The Association between Inappropriate Weight Control Behaviors and Suicide Ideation and Attempt among Korean Adolescents. AB - Suicide is a leading cause of death among adolescents globally, and body weight is also a recognized reason for adolescent suicide. Therefore, we investigated the association between weight control behaviors (WCB) and suicide ideation and attempt, focusing on inappropriate weight control measures. We used data from the 2014 Korea Youth Risk Behavior Web-based Survey, representing a total of 35,224 boys and 34,361 girls aged 12 to 18 years. Adolescents were classified into groups based on WCB: appropriate WCB, inappropriate WCB, and no WCB. We performed logistic regression models to examine associations between WCB and suicide ideation and attempt, controlling for covariates. Both boys and girls with inappropriate WCB were more likely to report suicide ideation and attempt. Underweight and normal weight boys with inappropriate WCB were more likely to think or attempt suicide, and underweight girls with inappropriate WCB were also more likely to attempt suicide. Among five common WCB combinations, the combination of "regular exercise, fasting, eating less" was highly associated with suicide ideation and attempt. We confirmed that inappropriate WCB is associated with suicide ideation and attempt among Korean adolescents. Given the high incidence rate of suicide among adolescents and the adverse effect of inappropriate WCB, encouraging adolescents to control their weight in healthy ways is imperative. PMID- 27550478 TI - Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea. AB - Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population. PMID- 27550480 TI - Ossification of the Medial Clavicular Epiphysis on Chest Radiographs: Utility and Diagnostic Accuracy in Identifying Korean Adolescents and Young Adults under the Age of Majority. AB - The aim of our study was to evaluate the utility and diagnostic accuracy of the ossification grade of medial clavicular epiphysis on chest radiographs for identifying Korean adolescents and young adults under the age of majority. Overall, 1,151 patients (age, 16-30) without any systemic disease and who underwent chest radiography were included for ossification grading. Two radiologists independently classified the ossification of the medial clavicular epiphysis from chest radiographs into five grades. The age distribution and inter observer agreement on the ossification grade were assessed. The diagnostic accuracy of the averaged ossification grades for determining whether the patient is under the age of majority was analyzed by using receiver operating characteristic (ROC) curves. Two separate inexperienced radiologists assessed the ossification grade in a subgroup of the patients after reviewing the detailed descriptions and image atlases developed for ossification grading. The median value of the ossification grades increased with increasing age (from 16 to 30 years), and the trend was best fitted by a quadratic function (R-square, 0.978). The inter-observer agreements on the ossification grade were 0.420 (right) and 0.404 (left). The area under the ROC curve (AUC) was 0.922 (95% CI, 0.902-0.942). The averaged ossification scores of 2.62 and 4.37 provided 95% specificity for a person < 19 years of age and a person >= 19 years of age, respectively. A preliminary assessment by inexperienced radiologists resulted in an AUC of 0.860 (95% CI, 0.740-0.981). The age of majority in Korean adolescents and young adults can be estimated using chest radiographs. PMID- 27550481 TI - Characteristics of Workplace Injuries among Nineteen Thousand Korean Firefighters. AB - To determine the actual firefighter injury statistics in Korea, we conducted a survey on the nature of on-duty injuries among all male firefighters in Korea. We distributed questionnaires to all Korean male firefighters via email, and data from the 19,119 workers that responded were used for data analysis. The job types were categorized into fire suppression, emergency medical service (EMS) and officers. As estimated of age standardized injury prevalence per one thousand workers, 354 fire extinguishing personnel, 533 EMS workers, and 228 officers experienced one or more injuries during the previous 12 months. The odds ratio (95% confidence interval) of injuries was 1.86 (1.61-2.15) for fire suppression and 2.93 (2.51-3.42) for EMS personnel compared to officers after adjusting for age, marital status, smoking habit and career period. Age standardized absence days from work due to injuries per one thousand workers were 1,120, 1,337, and 676 for fire suppression, EMS and officers, respectively. Car accident (24.5%) was the most common cause and wound (42.3%) was the most common type of injuries. Our nationwide representative study showed that fire suppression and EMS workers are at greater risk of on-duty injuries compared to officers. We observed different injury characteristics compared to those reported in other countries. PMID- 27550482 TI - A Survey of Antimicrobial Stewardship Programs in Korea, 2015. AB - The study was conducted to evaluate the Antibiotic Stewardship Program (ASP) in Korean hospitals compared with the previous two surveys in 2006 and 2012. The information on ASPs was collected through an online-based survey sent by e-mail to 192 infectious diseases specialists in 101 Korean hospitals in September 2015. Fifty-four hospitals (53.5%, 54/101) responded to the online survey. One infectious diseases specialist was employed in 30 (55.6%) of the 54 hospitals, and they were in charge of ASPs in hospitals with the program. Fifty of the 54 hospitals (92.6%) had ASPs and the same number of hospitals was conducting a preauthorization-of-antibiotics-use program. Although most hospitals adopted preauthorization strategies for more antibiotics in 2015 than in 2012 (median 14 in 2015; 13 in 2012), a limited number of antibiotics were under control. The number of per oral and parenteral antibiotics available in hospitals in 2015 decreased compared to 2006 and 2012. The number of hospitals performing a retrospective or prospective qualitative drug use evaluation of antibiotic use increased from 2006 to 2015. Manpower in charge of antibiotic stewardship in most hospitals was still very limited and ASPs heavily depended on preauthorization-of antibiotics-use programs in this survey. In conclusion, there leaves much to be desired in ASPs in Korea in 2015. PMID- 27550483 TI - Immunoglobulin G Subclass Deficiencies in Adult Patients with Chronic Airway Diseases. AB - Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary immunodeficiency disease (PI) in adults. The biological significance of IgGSCD in patients with chronic airway diseases is controversial. We conducted a retrospective study to characterize the clinical features of IgGSCD in this population. This study examined the medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012. Subjects were classified according to the 10 warning signs developed by the Jeffrey Modell Foundation (JMF) and divided into two patient groups: group I (n = 17) met >= two JMF criteria, whereas group II (n = 42) met none. IgG3 deficiency was the most common subclass deficiency (88.1%), followed by IgG4 (15.3%). The most common infectious complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis. The numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, respectively). The follow-up mean forced expiratory volume (FEV1) level in group I was significantly lower than it was at baseline despite treatment of asthma or COPD (P = 0.036). In conclusion, IgGSCD is an important PI in the subset of patients with chronic airway diseases who had recurrent upper and lower respiratory infections as they presented with exacerbation-prone phenotypes, decline in lung function, and subsequently poor prognosis. PMID- 27550484 TI - Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study. AB - The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout. PMID- 27550485 TI - Prognostic Impact of Changes in Adipose Tissue Areas after Colectomy in Colorectal Cancer Patients. AB - There have been few studies assessing the changes in the body components of patients after colectomy in colorectal cancer (CRC). The purpose of this study was to verify the trends in the adipose tissue areas of CRC patients before and after surgery and to determine their clinical relevance. Computed tomography (CT) assessed subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas were recorded before and after curative resection in stage I to III CRC patients. Changes in the adipose tissue were assessed by calculating the difference in the adipose tissue area between preoperative CT and the most recent postoperative CT, which is disease-free state. Regarding obesity before surgery, there were no prognostic effect of body mass index (BMI), VAT and SAT, and 47.3% of patients had increases in VAT after colectomy. By multivariate analysis, adjusting sex, age, stage, differentiation, VAT change was the only obesity related factor to predict the prognosis, that patients who had increase in VAT after colectomy had better overall survival (HR, 0.557; 95% CI, 0.317-0.880) and disease-free survival (HR, 0.602; 95% CI, 0.391-0.927). BMI and SAT change had no significant association. In subgroup analysis of stage III CRC patients, VAT change had significance for prognosis only in patients who had adjuvant chemotherapy but not in those who did not receive postoperative chemotherapy. Increase in visceral adipose tissue after surgery is a favorable predictor of prognosis for CRC patients. PMID- 27550486 TI - Incidence, Survival and Prevalence Statistics of Classical Myeloproliferative Neoplasm in Korea. AB - The nationwide statistical analysis of each disease of classical myeloproliferative neoplasm (MPN) in Korea has not been reported yet. To this end, we have analyzed incidence rates, survival rates and treatment pattern of polycythemia vera (PV), primary myelofibrosis (MF) and essential thrombocythemia (ET) using Korea National Cancer Incidence Database (KNCIDB) and Health Insurance Review and Assessment Service (HIRA) database. Between 2003 and 2011, a total of 4,342 new cases of MPN were reported to the KNCIDB. ET was the most common, followed by MF and PV. The crude incidence rates for PV, MF, and ET have increased during the period, reaching 0.40, 0.15, and 0.84 per 100,000, respectively. Five-year relative survival rate of all MPN patients was 89.3%, with lowest relative survival rate with MF (53.1%). The prevalence of each disease estimated from HIRA data also increased during the study period. Notably, ET was found to be most prevalent. The prescription rate of hydroxyurea and phlebotomy to PV, MF and ET patients remained constant over the period, and the prescription rate of hydroxyurea was higher in patients with age over 60 years. This is the first Korean nationwide statistics of MPN, using central registry data. This set of data can be utilized to compare the Korean MPN status to international data and guidelines. PMID- 27550487 TI - Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer. AB - Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan 1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma. PMID- 27550488 TI - The Association between Trunk Body Composition and Spinal Bone Mineral Density in Korean Males versus Females: a Farmers' Cohort for Agricultural Work-Related Musculoskeletal Disorders (FARM) Study. AB - The purpose of this study was proposed to identify the association of trunk body composition with spinal bone mineral density (BMD) in Korean male and female farmers. A total of 523 Korean farmers (259 males, 44 premenopausal females, and 220 postmenopausal females) were recruited. Computed tomography scans were acquired at the mid-L4 vertebral level, and total trunk muscle mass (TMM, cm3), back muscle mass (BMM), and abdominal wall muscle mass (AMM), total trunk fat mass (TFM), visceral fat mass (VFM), and subcutaneous fat mass (SFM) were assessed. Spinal BMD (g/cm2) was estimated from dual-energy X-ray absorptiometry at the L4 level. In terms of muscle mass, spinal BMD was significantly correlated with all the components of the trunk muscle mass (r = 0.171-0.360; P < 0.05, P < 0.001) in female farmers, while only with AMM (r = 0.181; P < 0.01) in male farmers. In terms of fat mass, spinal BMD was significantly correlated with all components of the trunk fat mass (r = 0.142-0.424; P < 0.05, P < 0.001) in male and premenopausal female farmers, while only with VFM (r = 0.132; P < 0.05) in postmenopausal females. Adjusted multivariate regression analysis showed that AMM in male and post-menopausal female farmers was closely associated with spinal BMD. There may be positive associations between trunk muscle and fat mass and spinal BMD with sexual dimorphism, and abdominal wall muscle mass was an explanatory variable closely related to spinal BMD in Korean farmers. Registered at the Clinical Research Information Service (CRIS, http://cris.nih.go.kr), number KCT0000829. PMID- 27550489 TI - The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis. AB - Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics. PMID- 27550490 TI - The Clinical Outcomes of Lower Gastrointestinal Bleeding Are Not Better than Those of Upper Gastrointestinal Bleeding. AB - The incidence of lower gastrointestinal bleeding (LGIB) is increasing; however, predictors of outcomes for patients with LGIB are not as well defined as those for patients with upper gastrointestinal bleeding (UGIB). The aim of this study was to identify the clinical outcomes and the predictors of poor outcomes for patients with LGIB, compared to outcomes for patients with UGIB. We identified patients with LGIB or UGIB who underwent endoscopic procedures between July 2006 and February 2013. Propensity score matching was used to improve comparability between LGIB and UGIB groups. The clinical outcomes and predictors of 30-day rebleeding and mortality rate were analyzed between the two groups. In total, 601 patients with UGIB (n = 500) or LGIB (n = 101) were included in the study, and 202 patients with UGIB and 101 patients with LGIB were analyzed after 2:1 propensity score matching. The 30-day rebleeding and mortality rates were 9.9% and 4.5% for the UGIB group, and 16.8% and 5.0% for LGIB group, respectively. After logistic regression analysis, the Rockall score (P = 0.013) and C-reactive protein (CRP; P = 0.047) levels were significant predictors of 30-day mortality in patients with LGIB; however, we could not identify any predictors of rebleeding in patients with LGIB. The clinical outcomes for patients with LGIB are not better than clinical outcomes for patients with UGIB. The clinical Rockall score and serum CRP levels may be used to predict 30-day mortality in patients with LGIB. PMID- 27550491 TI - Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children. AB - We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 +/- 10.7 vs. 8.0 +/- 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID- 27550492 TI - Effect of Sleep Deprivation on the Male Reproductive System in Rats. AB - There has been no study reporting on the influence of sleep deprivation on the male reproductive system including sperm quality. In this study, we hypothesized that sleep deprivation could lead to adverse effect on the male reproductive system. The rats were divided into three groups: 1) control (home-cage, n = 10); 2) SD4 (sleep deprivation for 4 days, n = 10); and 3) SD7 (sleep deprivation for 7 days, n = 10). Sleep deprivation was performed by a modified multiple platform method. Sperm quality (sperm motion parameters and counts), hormone levels (corticosterone and testosterone), and the histopathology of testis were evaluated and compared between the three groups. A statistically significant reduction (P = 0.018) was observed in sperm motility in the SD7 group compared to those of the control group. However, there were no significant differences in other sperm motion parameters, or in sperm counts of the testis and cauda epididymis between three groups. Compared with the control group, the SD4 (P = 0.033) and SD7 (P = 0.002) groups exhibited significant increases of corticosterone levels, but significant decreases of testosterone levels were found in the SD4 (P = 0.001) and SD7 (P < 0.001) groups. Seminiferous tubular atrophy and/or spermatid retention was partially observed in the SD4 and SD7 groups, compared with the normal histopathology of the control group. Sleep deprivation may have an adverse effect on the male reproductive system in rats. PMID- 27550493 TI - The Change of Stretched Penile Length and Anthropometric Data in Korean Children Aged 0-14 Years: Comparative Study of Last 25 Years. AB - There has been a great improvement in height and weight of Korean children owing to economic development over the last 25 years. This study aimed to evaluate the penile length of Korean children today and to compare it with a previous Korean study reported in 1987. The cross-sectional study was conducted with 909 Korean boys aged 0-14 years who had been brought to outpatient clinics of five tertiary hospitals (Busan, Ulsan, and Changwon) between September 2013 and May 2015. The stretched penile length (SPL) was measured and the testicular size was measured using orchidometry (mL). Student's t-test or Mann-Whitney U test was used to compare the result of our study and the study reported in 1987. SPL of Korean children gradually increased from 4.1 +/- 0.8 cm at 0-1 year old to 9.6 +/- 3.0 cm at 13-14 years old, the most rapidly during the age of 13. While body weight and testicular size significantly increased from 1987 in most of age groups, there were no significant changes in SPL although there was in some age groups. Height decreased in the infants < 1 year old and increased in the children > 6 years old. With the great economic development over the last quarter century in Korea, height, body weight, and testicular size of children significantly increased but there was no significant change in SPL except penile growth pattern. PMID- 27550494 TI - Which Stratum of Urban Elderly Is Most Vulnerable for Dementia? AB - Many factors associated with a patient's lifestyle may disrupt timely access to dementia diagnosis and management. The aim of this study was to compare characteristics of lifestyle factors at the time of initial evaluation for dementia across degrees of dementia, and to identify risk factors relating to late detection of dementia, in order to understand the various lifestyle barriers to timely recognition of the disease. We reviewed medical records of 1,409 subjects who were diagnosed as dementia among 35,723 inhabitants of Gwangjin-gu. Dementia severity was divided into three degrees. Age, sex, education, income, smoking, heavy drinking, physical activity, religion, and living conditions were evaluated. There was a significantly greater proportion of individuals who were old age, female, less educated, who had never smoked or drank heavily, without physical activity, with no religious activity and living with family other than spouse in the severe dementia group. The lifestyle risks of late detection were old age, lower education, less social interactions, less physical activity or living with family. We can define this group of patients as the vulnerable stratum to dementia evaluation. Health policy or community health services might find ways to better engage patients in this vulnerable stratum to dementia. PMID- 27550495 TI - Effect of Brace to Osteoporotic Vertebral Fracture: a Meta-Analysis. AB - Brace is one of the most commonly used interventions to manage osteoporotic vertebral fracture. However, its authentic effectiveness remains unclear. The aim of this study was to investigate the efficacy of brace in patients with osteoporotic vertebral fractures. We conducted a literature review and meta analysis following the guideline and handbook of the Cochrane collaboration. Ten published articles were included in this study and data from 4 randomized controlled trials were analyzed. Low quality evidence proved using Spinomed brace could bring large and significant beneficial effect to patients with sub-acute osteoporotic vertebral fractures. Very low quality evidence proved no significant difference between Spinomed orthosis, rigid brace and soft brace when they were used in patients with acute fractures. Therefore, it might be applicable to recommend middle term use of Spinomed orthosis to patients with subacute fracture. In addition, this study emphasized the need for high quality randomized controlled trials. PMID- 27550496 TI - Decreased Lumbar Lordosis and Deficient Acetabular Coverage Are Risk Factors for Subchondral Insufficiency Fracture. AB - Subchondral insufficiency fracture (SIF) of the femoral head occurs in the elderly and recipients of organ transplantation. Osteoporosis and deficient lateral coverage of the acetabulum are known risk factors for SIF. There has been no study about relation between spinopelvic alignment and anterior acetabular coverage with SIF. We therefore asked whether a decrease of lumbar lordosis and a deficiency in the anterior acetabular coverage are risk factors. We investigated 37 patients with SIF. There were 33 women and 4 men, and their mean age was 71.5 years (59-85 years). These 37 patients were matched with 37 controls for gender, age, height, weight, body mass index and bone mineral density. We compared the lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope, acetabular index, acetabular roof angle, acetabular head index, anterior center-edge angle and lateral center-edge angle. Lumbar lordosis, pelvic tilt, sacral slope, lateral center edge angle, anterior center edge angle, acetabular index and acetabular head index were significantly different between SIF group and control group. Lumbar lordosis (OR = 1.11), lateral center edge angle (OR = 1.30) and anterior center edge angle (OR = 1.27) had significant associations in multivariate analysis. Decreased lumbar lordosis and deficient anterior coverage of the acetabulum are risk factors for SIF as well as decreased lateral coverage of the acetabulum. PMID- 27550497 TI - Reduced Mortality by Physician-Staffed HEMS Dispatch for Adult Blunt Trauma Patients in Korea. AB - The aim of this study was to investigate the efficiency of domestic physician staffed helicopter emergency medical service (HEMS) for the transport of patients with severe trauma to a hospital. The study included patients with blunt trauma who were transported to our hospital by physician-staffed HEMS (Group P; n = 100) or nonphysician-staffed HEMS (Group NP; n = 80). Basic patient characteristics, transport time, treatment procedures, and medical treatment outcomes assessed using the Trauma and Injury Severity Score (TRISS) were compared between groups. We also assessed patients who were transported to the hospital within 3 h of injury in Groups P (Group P3; n = 50) and NP (Group NP3; n = 74). The severity of injury was higher, transport time was longer, and time from hospital arrival to operation room transfer was shorter for Group P than for Group NP (P < 0.001). Although Group P patients exhibited better medical treatment outcomes compared with Group NP, the difference was not statistically significant (P = 0.134 vs. 0.730). However, the difference in outcomes was statistically significant between Groups P3 and NP3 (P = 0.035 vs. 0.546). Under the current domestic trauma patient transport system in South Korea, physician-staffed HEMS are expected to increase the survival of patients with severe trauma. In particular, better treatment outcomes are expected if dedicated trauma resuscitation teams actively intervene in the medical treatment process from the transport stage and if patients are transported to a hospital to receive definitive care within 3 hours of injury. PMID- 27550498 TI - Anaphylaxis to Polyethylene Glycol (Colyte(r)) in a Patient with Diverticulitis. AB - Polyethylene glycols (PEGs) are believed to be chemically inert agents, but larger PEG polymers could have immunogenicity. A 39-year-old man was referred to emergency room for loss of consciousness and dyspnea after taking of PEG-3350 (Colyte(r)). In laboratory findings, the initial serum tryptase level was increased to 91.9 mg/L (normal range: 0.00-11.40 mg/L) without any other laboratory abnormalities. The intradermal test with 10 mg/mL Colyte(r) showed a 5 * 5 mm wheal, but basophil activation and histamine releasability tests were negative. PEG-3350 is widely used as an osmotic laxative due to its lack of absorption from the gastrointestinal tract. However, the loss of mucosal integrity at gastrointestinal membrane such as diverticulitis may be a predisposing factor for anaphylaxis to Colyte(r). We report a case of anaphylaxis induced by the ingestion of PEG-3350 in a patient with diverticulitis which might be a risk factor of anaphylaxis. PMID- 27550499 TI - Hirayama Disease with Proximal Involvement. AB - Hirayama disease is a slowly progressing benign motor neuron disease that affects the distal upper limb. A 29-year-old man visited the hospital with a 1-year history of weakened left proximal upper limb. He was diagnosed with Hirayama disease 9 years ago, while there was no further progression of the muscle weakness afterward. Atrophy and weakness was detected in proximal upper limb muscles. Magnetic resonance imaging and somatosensory evoked potentials were normal. Needle electromyography showed abnormal findings in proximal upper limb muscles. Our patient had Hirayama disease involving the proximal portion through secondary progression. Clinical manifestation and accurate electromyography may be useful for diagnosis. Rare cases with progression patterns as described here are helpful and have clinical meaning for clinicians. PMID- 27550500 TI - Letter to the Editor: Chest Compression Rate, Rescuer's Fatigue and Patient's Survival. PMID- 27550501 TI - The Author's Response: Response to the Comment: Chest Compression Rate, Rescuer's Fatigue and Patient's Survival. PMID- 27550502 TI - Whole-cell Proteus mirabilis urease inhibition by aminophosphinates for the control of struvite formation. AB - The study evaluated the in vitro impact of a series of aminophosphinic urease inhibitors on Proteusmirabilis. The group of compounds comprised structurally diverse analogues of diamidophosphate built on an N-C-P scaffold. The influence of urease inhibition on urea-splitting activity was assessed by whole-cell pH static kinetic measurements. The potential to prevent struvite formation was determined by monitoring changes in pH and ionic composition of artificial urine medium during P. mirabilis growth. The most active compounds exhibited stronger positive effect on urine stability than the acknowledged inhibitor acetohydroxamic acid. The high anti-ureolytic and pH-stabilizing effect of urease inhibitors 4 and 14 was well correlated with their reported kinetic properties against pure urease from P. mirabilis (Ki values of 0.62+/-0.09 and 0.202+/-0.057 uM, respectively, compared to 5.7+/-0.4 uM for acetohydroxamic acid). The effect of repressed ureolysis upon the viability of Proteus cells was studied using MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] metabolic efficiency assay and LIVE/DEAD fluorescent staining. Most of the compounds caused whole-cell dehydrogenase activity loss; four structures (1, 2, 4 and 14) reduced the culture viability by nearly 70 % at 1 mM concentration. Results of dual fluorescent staining suggested that besides urea-splitting prevention, the structures additionally exerted an outer-membrane-destabilizing effect. PMID- 27550503 TI - Stearoyl-CoA desaturase-1 and adaptive stress signaling. AB - Stearoyl-CoA desaturase (SCD), the central enzyme in the biosynthesis of monounsaturated fatty acids, introduces a cis-Delta9 double bond into saturated fatty acids. SCD-1 has been proposed as promising target for the treatment of cancer, skin disorders and metabolic diseases, and strong efforts have been made during the last decade to develop clinical drug candidates. While the regulation and biological implications of SCD-1 have been extensively reviewed, the molecular mechanisms through which SCD-1 mediates cellular responses remained a mystery. An important aspect seems to be that SCD-1 induces adaptive stress signaling that maintains cellular persistence and fosters survival and cellular functionality under distinct pathological conditions. Here, we will first provide an overview about the function, regulation, structure and mechanism of SCD-1 and then focus on mitogenic and stress-related signal transduction pathways orchestrated by SCD-1. Moreover, we will discuss molecular mechanisms and potential lipid factors that link SCD-1 activity with initial signal transduction. PMID- 27550504 TI - Vascular Patency: A Biomarker and Clinical Target Quantified with High Resolution MRI and Novel Cellular Pathways. PMID- 27550505 TI - Successfully treated superficial basal cell carcinomas with ingenol mebutate 0.05% gel: Report of twenty cases. AB - Surgery is the therapy of choice in the guidelines to treat basal cell carcinomas (BCCs) but a variety of non-surgical options are available. The objective of this study is to evaluate the efficacy and safety of ingenol mebutate 0.05% gel for the treatment of superficial BCCs. We accepted twenty patients with superficial BCCs on the body and we treated them once daily for two consecutive days with ingenol mebutate 0.05% gel. We examined the lesions at the screening visit and after four days from the gel application to describe the local skin reaction due to the therapy. Then we followed the patients after two and six months from the first visit. All the lesions were clinically and dermoscopically documented with a digital camera and we used the LSR (local skin reaction) grading scale based on a 0-4 numerical index of severity with specific clinical parameters and a characteristic photographic image for each rating, to assess the local side effects related to the therapy. PMID- 27550506 TI - The development of healthcare use among a cohort of Finnish social assistance clients: testing the social selection hypothesis. AB - This article examines the association between healthcare use and receipt of social assistance. It focuses on asking to what extent the use of healthcare (seen as a proxy for health status) leads to social assistance. This is answered by describing the use of healthcare services among a cohort of Finnish social assistance clients before, during and after the first receipt of benefit by means of fixed-effects logistic regression. Using register data, the study follows a group of social assistance recipients from 2005 to 2011 and compares their use of healthcare to those not claiming social assistance during this same period and analyses how their use of health services develops over time. The results show that recipients use public healthcare clearly more than non-recipients, but they do so already prior to the first social assistance receipt. This partly confirms the social selection hypothesis according to which health problems lead to low income. However, the results do not exclude the existence of social causation. The causality is most likely bi-directional. The findings of the descriptive analyses are corroborated by a fixed-effects logistic regression analysis: the use of healthcare services increases the probability of receiving social assistance in the following month. PMID- 27550507 TI - Prenatal whole exome sequencing: the views of clinicians, scientists, genetic counsellors and patient representatives. AB - OBJECTIVE: Focus groups were conducted with individuals involved in prenatal diagnosis to determine their opinions relating to whole exome sequencing in fetuses with structural anomalies. METHOD: Five representatives of patient groups/charities (PRGs) and eight clinical professionals (CPs) participated. Three focus groups occurred (the two groups separately and then combined). Framework analysis was performed to elicit themes. A thematic coding frame was identified based on emerging themes. RESULTS: Seven main themes (consent, analysis, interpretation/reinterpretation of results, prenatal issues, uncertainty, incidental findings and information access) with subthemes emerged. The main themes were raised by both groups, apart from 'analysis', which was raised by CPs only. Some subthemes were raised by PRGs and CPs (with different perspectives). Others were raised either by PRGs or CPs, showing differences in patient/clinician agendas. CONCLUSIONS: Prenatal consent for whole exome sequencing is not a 'perfect' process, but consent takers should be fully educated regarding the test. PRGs highlighted issues involving access to results, feeling that women want to know all information. PRGs also felt that patients want reinterpretation of results over time, whilst CPs felt that interpretation should be performed at the point of testing only. (c) 2016 John Wiley & Sons, Ltd. PMID- 27550508 TI - Supermarkets criticise obesity strategy's lack of mandatory restrictions on sugar. PMID- 27550509 TI - Disrupted White Matter Microstructure and Mood Disorders after Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is associated with an elevated frequency of mood disorders that may, in part, be explained by changes in white-matter microstructure. This study is the first to examine the relationship between mood disorders and white-matter pathology in a sample of patients with mild to severe TBI using a standardized psychiatric interview. This study reports on a sub sample of 29 individuals recruited from a large prospective study that examined the evolution of psychiatric disorders following complicated, mild to severe TBI. Individuals with TBI were also compared with 23 healthy control participants. Individuals were invited to complete the Structured Clinical Interview for DSM-IV Disorders (SCID) to diagnose psychiatric disorders. Participants who developed a mood disorder within the first 3 years were categorized into a TBI-Mood group. Diffusion tensor tractography assessed white matter microstructure using atlas based tract-averaged and along-tract approaches. Fractional anisotropy (FA) was used as the measure of white-matter microstructure. TBI participants with and without a mood disorder did not differ in regard to injury severity and other background factors. Nevertheless, TBI participants diagnosed with a mood disorder displayed significantly lower tract-averaged FA values for the right arcuate fasciculus (p = 0.011), right inferior longitudinal fasciculus (p = 0.009), and anterior segments I (p = 0.0004) and II (p = 0.007) of the corpus callosum, as well as the left (p = 0.014) and right (p = 0.015) fronto-occipital longitudinal fasciculi. The pattern of white matter disruption identified in the current study provides further support for a neurobiological basis of post-TBI mood disorders. Greater understanding of individuals' underlying neuropathology may enable better characterization and prediction of mood disorders. Integration of neuropathology may also inform the potential efficacy of pharmacological and psychological interventions. PMID- 27550510 TI - Focal nodular hyperplasia: our experience of 53 Japanese cases. AB - PURPOSE: Contrast-enhanced ultrasound (CEUS) is a very sensitive diagnostic tool in characterizing liver tumors. It is especially useful in the diagnosis of focal nodular hyperplasia (FNH) of the liver. According to the previous reports, FNH is common in young women, and it is usually diagnosed by MRI. The majority of the previous reports come from European countries, and a very few studies of large series designed to describe the clinical features in Japanese patients have been reported. The aim of this study was to (a) describe the clinical features in 53 patients (59 lesions) diagnosed with CEUS and (b) compare the data with those from the previous reports. METHODS: The medical data from 53 patients diagnosed on the basis of typical CEUS findings at our institution and affiliated hospitals were reviewed, and their clinical data were analyzed. RESULTS: (1) The medical data from 53 cases showed a slight male predilection, with 30 male cases (57 %) and 23 female cases (43 %), although the occurrence in both sexes was equal. FNH cases were distributed throughout all generations in both sexes, mostly concentrated in the age of 30-60 years old, and metabolic cases were more common in men than in women (4 vs 0). (2) The lesions were small (mean: 23 mm) and distributed throughout the whole liver. (3) Lesion size was not influenced by age in either sex. (4) A rapid draining to the hepatic vein was recognized in five out of 59 lesions (8 %). CONCLUSIONS: Our data indicate that FNH occurs slightly more frequently in men than in women in Japan. It occurs also at any age in both sexes, but the mean lesion size was smaller in our series than in the previous reports. Metabolic disease was seen only in male FNH patients. A direct communication between the FNH lesion and the hepatic vein is diagnostically worth noting. PMID- 27550511 TI - Aortic events in a nationwide Marfan syndrome cohort. AB - BACKGROUND: Marfan syndrome is associated with morbidity and mortality due to aortic dilatation and dissection. Preventive aortic root replacement has been the standard treatment in Marfan syndrome patients with aortic dilatation. In this study, we present aortic event data from a nationwide Marfan syndrome cohort. METHOD: The nationwide cohort of Danish Marfan syndrome patients was established from the Danish National Patient Registry and the Cause of Death Register, where we retrieved information about aortic surgery and dissections. We associated aortic events with age, sex, and Marfan syndrome diagnosis prior or after the first aortic event. RESULTS: From the total cohort of 412 patients, 150 (36.4 %) had an aortic event. Fifty percent were event free at age 49.6. Eighty patients (53.3 %) had prophylactic surgery and seventy patients (46.7 %) a dissection. The yearly event rate was 0.02 events/year/patient in the period 1994-2014. Male patients had a significant higher risk of an aortic event at a younger age with a hazard ratio of 1.75 (CI 1.26-2.42, p = 0.001) compared with women. Fifty-three patients (12.9 %) were diagnosed with MFS after their first aortic event which primarily was aortic dissection [n = 44 (83.0 %)]. CONCLUSION: More than a third of MFS patients experienced an aortic event and male patients had significantly more aortic events than females. More than half of the total number of dissections was in patients undiagnosed with MFS at the time of their event. This emphasizes that diagnosing MFS is lifesaving and improves mortality risk by reducing the risk of aorta dissection. PMID- 27550512 TI - Echocardiographic correlates of left ventricular filling pressures and acute cardio-renal syndrome in ST segment elevation myocardial infarction patients. AB - OBJECTIVE: Increased transmitral flow velocity (E) to the early mitral annulus velocity (e') ratio (E/e'), signifying increased cardiac filling pressure, was previously found to be associated with deterioration of renal function in patients with congestive heart failure. No study, however, included patients with acute myocardial ischemia. We hypothesized that elevated E/e' ratio would be associated with an increased risk of acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). STUDY DESIGN AND METHODS: We conducted a retrospective study of 804 consecutive STEMI patients between June 2012 and December 2015 who underwent primary PCI and had a comprehensive echocardiographic examination performed within 72 h of hospital admission. Patients were stratified according to E/e' ratio above and <=15, and assessed for AKI using the KDIGO criteria, defined as either a serum creatinine rise >0.3 mg/dl, or an increase in serum creatinine >=1.5 times baseline. RESULTS: Patients with E/e' ratio >15 had lower left ventricular (LV) ejection fraction, higher systolic pulmonary artery pressures, as well as right atrial pressures, and demonstrated worse in-hospital outcomes. Patients with E/e' ratio >15 had more AKI complicating STEMI (27 vs. 7 %; p < 0.001). In multivariate logistic regression model, E/e' ratio >15 was independently associated with AKI (OR = 1.87, 95 % CI 0.99-3.52; p = 0.05). Other variables associated with AKI included diabetes, LV ejection fraction, and glomerular filtration rate. CONCLUSIONS: Among STEMI patients undergoing primary PCI, the early E/e' ratio >15 was associated with increased risk for AKI. PMID- 27550513 TI - Anaplastic Transformation of Papillary Thyroid Carcinoma Only Seen in Pleural Metastasis: A Case Report with Review of the Literature. AB - Anaplastic transformation of papillary thyroid carcinoma (PTC) at distant metastatic sites is extremely rare, and there have been fewer than 20 reported cases in the literature. A 61-year-old woman presented with 1-week history of dyspnea. Her past medical history was remarkable because, 19 years ago, she underwent nearly total thyroidectomy and radical neck dissection due to PTC. Computed tomography of the chest revealed a 1.7 cm nodule in the lung and diffuse pleural thickening. Gun biopsy of the lung nodule revealed metastatic PTC with typical histology. However, the pleural biopsy predominantly showed anaplastic pleomorphic and spindle sarcomatoid carcinoma with microscopic focus of PTC. Immunohistochemical results showed both anaplastic sarcomatoid and PTC components positive for TTF-1, galectin-3 and PAX-8, thus supporting anaplastic transformation of PTC at the metastatic site. Subsequently the patient received 1 cycle of cisplatin-based chemotherapy but died from the disease 4 months after diagnosis. Although it is rare, anaplastic transformation of PTC should be considered during differential diagnosis of patients who present with exclusive sarcomatoid morphology at metastatic sites and have a history of PTC. We report another case of anaplastic transformation of PTC, found at pleural metastasis, together with the immunohistochemical profile and a literature review. PMID- 27550515 TI - Seven Reasons Why I Am Bullish on the Future of Geriatrics in America: Urgency and Opportunity Converge in a Perfect Storm. PMID- 27550514 TI - A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes. AB - Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s. PMID- 27550516 TI - The Relationship Between Dietary Acculturation and Type 2 Diabetes Risk Among Asian Indians in the U.S. AB - Asian Indians have a high prevalence of type 2 diabetes in the U.S. (17.4-29 %). This study examined the relationship between dietary acculturation of Asian Indians in the U.S. and their future risk for type 2 diabetes. A validated Asian Indian Dietary Acculturation Measure (AIDAM) and the Finnish Diabetes Risk Score (FINDRISC) were completed by 153 Asian Indians in the U.S. via a cross-sectional web-survey. Correlations and relative risk ratios were used to examine the association between AIDAM and FINDRISC. A significantly larger proportion of Non Indian Oriented participants (44.7 %) had higher FINDRISC scores (scores 7-26) compared to the Asian Indian Oriented group (27.9 %) (p = .024), and also had increased relative predictive risk for type 2 diabetes (relative risk ratio = 1.6). A positive association between dietary acculturation and diabetes risk was evident in our sample, which highlights the importance of assessing dietary acculturation in non-native groups when investigating type 2 diabetes risk factors. PMID- 27550517 TI - PrP-containing aggresomes are cytosolic components of an ER quality control mechanism. AB - Limited detoxification capacity often directs aggregation-prone, potentially hazardous, misfolded proteins to be deposited in designated cytosolic compartments known as 'aggresomes'. The roles of aggresomes as cellular quality control centers, and the cellular origin of the deposits contained within these structures, remain to be characterized. Here, we utilized the observation that the prion protein (PrP, also known as PRNP) accumulates in aggresomes following the inhibition of folding chaperones, members of the cyclophilin family, to address these questions. We found that misfolded PrP molecules must pass through the endoplasmic reticulum (ER) in order to be deposited in aggresomes, that the Golgi plays no role in this process and that cytosolic PrP species are not deposited in pre-existing aggresomes. Prior to their deposition in the aggresome, PrP molecules lose the ER localization signal and have to acquire a GPI anchor. Our discoveries indicate that PrP aggresomes are cytosolic overflow deposition centers for the ER quality control mechanisms and highlight the importance of these structures for the maintenance of protein homeostasis within the ER. PMID- 27550518 TI - The microtubule-binding and coiled-coil domains of Kid are required to turn off the polar ejection force at anaphase. AB - Mitotic chromosomes move dynamically along the spindle microtubules using the forces generated by motor proteins such as chromokinesin Kid (also known as KIF22). Kid generates a polar ejection force and contributes to alignment of the chromosome arms during prometaphase and metaphase, whereas during anaphase, Kid contributes to chromosome compaction. How Kid is regulated and how this regulation is important for chromosome dynamics remains unclear. Here, we address these questions by expressing mutant forms of Kid in Kid-deficient cells. We demonstrate that Cdk1-mediated phosphorylation of Thr463 is required to generate the polar ejection force on Kid-binding chromosomes, whereas dephosphorylation of Thr463 prevents generation of the ejection force on such chromosomes. In addition to activation of the second microtubule-binding domain through dephosphorylation of Thr463, the coiled-coil domain is essential in suspending generation of the polar ejection force, preventing separated chromosomes from becoming recongressed during anaphase. We propose that phosphorylation of Thr463 switches the mitotic chromosome movement from an anti-poleward direction to a poleward direction by converting the Kid functional mode from polar-ejection-force-ON to -OFF during the metaphase-anaphase transition, and that both the second microtubule-binding domain and the coiled-coil domain are involved in this switching process. PMID- 27550519 TI - ARHGEF10 directs the localization of Rab8 to Rab6-positive executive vesicles. AB - The function of ARHGEF10, a known guanine nucleotide exchange factor (GEF) for RhoA with proposed roles in various diseases, is poorly understood. To understand the precise function of this protein, we raised a monoclonal antibody against ARHGEF10 and determined its localization in HeLa cells. ARHGEF10 was found to localize to vesicles containing Rab6 (of which there are three isoforms, Rab6a, Rab6b and Rab6c), Rab8 (of which there are two isoforms, Rab8a and Rab8b), and/or the secretion marker neuropeptide Y (NPY)-Venus in a Rab6-dependent manner. These vesicles were known to originate from the Golgi and contain secreted or membrane proteins. Ectopic expression of an N-terminal-truncated ARHGEF10 mutant led to the generation of large vesicle-like structures containing both Rab6 and Rab8. Additionally, small interfering (si)RNA-mediated knockdown of ARHGEF10 impaired the localization of Rab8 to these exocytotic vesicles. Furthermore, the invasiveness of MDA-MB231 cells was markedly decreased by knockdown of ARHGEF10, as well as of Rab8. From these results, we propose that ARHGEF10 acts in exocytosis and tumor invasion in a Rab8-dependent manner. PMID- 27550521 TI - Sodium in feline nutrition. AB - High sodium levels in cat food have been controversial for a long time. Nonetheless, high sodium levels are used to enhance water intake and urine volume, with the main objective of reducing the risk of urolithiasis. This article is a review of current evidence of the putative risks and benefits of high dietary sodium levels. Its secondary aim is to report a possible safe upper limit (SUL) for sodium intake. The first part of the manuscript is dedicated to sodium physiology, with a focus on the mechanisms of sodium homeostasis. In this respect, there is only few information regarding possible interactions with other minerals. Next, the authors address how sodium intake affects sodium balance; knowledge of these effects is critical to establish recommendations for sodium feed content. The authors then review the consequences of changes in sodium intake on feline health, including urolithiasis, blood pressure changes, cardiovascular alterations and kidney disease. According to recent, long-term studies, there is no evidence of any deleterious effect of dietary sodium levels as high as 740 mg/MJ metabolizable energy, which can therefore be considered the SUL based on current knowledge. PMID- 27550520 TI - Collective migration and cell jamming in asthma, cancer and development. AB - Collective cellular migration within the epithelial layer impacts upon development, wound healing and cancer invasion, but remains poorly understood. Prevailing conceptual frameworks tend to focus on the isolated role of each particular underlying factor - taken one at a time or at most a few at a time - and thus might not be tailored to describe a cellular collective that embodies a wide palette of physical and molecular interactions that are both strong and complex. To bridge this gap, we shift the spotlight to the emerging concept of cell jamming, which points to only a small set of parameters that govern when a cellular collective might jam and rigidify like a solid, or instead unjam and flow like a fluid. As gateways to cellular migration, the unjamming transition (UJT) and the epithelial-to-mesenchymal transition (EMT) share certain superficial similarities, but their congruence - or lack thereof - remains unclear. In this Commentary, we discuss aspects of cell jamming, its established role in human epithelial cell layers derived from the airways of non-asthmatic and asthmatic donors, and its speculative but emerging roles in development and cancer cell invasion. PMID- 27550522 TI - Application of novel quantitative techniques for fluorodeoxyglucose positron emission tomography/computed tomography in patients with non-small-cell lung cancer. AB - AIM: Flurodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is routinely used in non-small-cell lung cancer. This study aims to assess the prognostic value of quantitative FDG-PET/CT parameters including standard uptake value (SUV), metabolic tumor volume (MTV) and total lesional glycolysis (TLG) in non-small-cell lung cancer. METHODS: A retrospective review of 92 nonsurgical patients with pathologically confirmed stage I-III non-small cell lung cancers treated with radical dose radiotherapy (>=50 Gy) was conducted. Metabolically active tumor regions on FDG-PET/CT scans were contoured manually. SUV, MTV and TLG were calculated for primary, nodal and whole-body disease. Univariate and multivariate (adjusting for age, sex, disease stage and primary tumor size in centimeters) Cox regression modeling were performed to assess the association between these parameters and both overall and progression-free survival (PFS). RESULTS: On univariate analysis, overall survival (OS) was significantly associated with primary MTV (P = 0.03), whole-body MTV (P = 0.02), whole-body maximum SUV (P = 0.05) and whole-body TLG (P = 0.03). PFS was significantly associated with primary MTV (P = 0.01), primary TLG (P = 0.04), whole-body MTV (P < 0.01) and whole-body TLG (P = 0.01). On multivariate analysis, OS was significantly associated with whole-body MTV (P = 0.05). PFS was significantly associated with whole-body MTV (P = 0.02) and whole-body TLG (P = 0.05). CONCLUSIONS: Whole-body MTV was significantly associated with overall and PFS, and whole-body TLG was significantly associated with PFS on multivariate analysis. These two parameters may be significant prognostic factors independent of other factors such as stage. SUV was not significantly associated with survival on multivariate analysis. PMID- 27550523 TI - Identification and Characterization of Complex Glycosylated Peptides Presented by the MHC Class II Processing Pathway in Melanoma. AB - The MHC class II (MHCII) processing pathway presents peptides derived from exogenous or membrane-bound proteins to CD4+ T cells. Several studies have shown that glycopeptides are necessary to modulate CD4+ T cell recognition, though glycopeptide structures in these cases are generally unknown. Here, we present a total of 93 glycopeptides from three melanoma cell lines and one matched EBV transformed line with most found only in the melanoma cell lines. The glycosylation we detected was diverse and comprised 17 different glycoforms. We then used molecular modeling to demonstrate that complex glycopeptides are capable of binding the MHC and may interact with complementarity determining regions. Finally, we present the first evidence of disulfide-bonded peptides presented by MHCII. This is the first large scale study to sequence glyco- and disulfide bonded MHCII peptides from the surface of cancer cells and could represent a novel avenue of tumor activation and/or immunoevasion. PMID- 27550524 TI - Can we consider cesarean myomectomy as a safe procedure without long-term outcome? AB - AIM: To investigate short- and long-term outcomes in women undergoing cesarean myomectomy (CM). METHODS: This was a retrospective study that explored short-term outcomes of women, who underwent cesarean operations with or without myomectomies (CM controls) in a single tertiary center throughout a 6-year-period. For long term outcomes, the mean duration of follow-up was 6.3 +/- 1.0 years. RESULTS: There were no differences among the CM (n= 91) and control groups (n = 60) considering mean change in hemoglobin and hematocrit levels, hemorrhage, as well as requirement for blood transfusions with a slightly increased operative time. Multiple myomas, and cervical and cornual localization were associated with an increased drop of hemoglobin and hematocrit (p < 0.05). Subsequent pregnancy and recurrence rates were 35% (32/91) and 5.5% (5/91), respectively. Preterm delivery (n = 1, 3.1%), uterine dehiscence (n = 1, 3.1%), placenta previa (n = 1, 3.1%) and mild-to-severe post-CM adhesions (n = 8, 25%) were observed in subsequent pregnancies. Recurrence was identified in five of the nonpregnant (5.5%) women, and three of these (4.1%) underwent an additional major surgery. There was no recurrence in subsequent pregnancies. CONCLUSION: The recurrence of myoma was relatively low following CM. Subsequent pregnancy is protective for recurrence of myoma without increased adhesion formation and obstetric complications. PMID- 27550525 TI - N-Heteroarylation of Optically Pure alpha-Amino Esters using the Pd-PEPPSI IPentCl -o-picoline Pre-Catalyst. AB - A robust, mild, and efficient method for the Pd-catalyzed N-heteroarylation of optically pure alpha-amino esters was developed. Dichloro[1,3-bis(2,6-di-3 pentylphenyl)imidazol-2-ylidene](o-picoline)palladium(II) (Pd-PEPPSI-IPentCl -o picoline; PEPPSI=pyridine enhanced pre-catalyst preparation, stabilization, and initiation) was shown to effectively couple a variety of amino acids as the tert butyl ester with heteroaryl chlorides in high yields and with excellent stereoretention of the acidic proton adjacent to the ester. Control experiments revealed that racemization is base-mediated, with no evidence of Pd-mediated beta hydride elimination when using Pd-PEPPSI-IPentCl , and that racemization occurs only after the product is formed, that is, the non-arylated starting amino ester does not deprotonate under our reaction conditions. Studies also revealed that increasing the steric bulk of the ester moiety on the amino acid (e.g., ethyl to tert-butyl) drastically slows racemization of the product. PMID- 27550526 TI - Role of omentectomy as part of radical surgery for gastric cancer. AB - BACKGROUND: A complete omentectomy is recommended as part of radical (sub)total gastrectomy for gastric cancer, but there is little evidence to suggest any survival benefit. The aim of this study was to evaluate the incidence of, and risk factors for, metastases in the greater omentum in patients undergoing gastrectomy for gastric cancer. METHODS: This was a multicentre prospective cohort study (OMEGA trial) of consecutive patients with gastric cancer undergoing (sub)total gastrectomy with complete en bloc omentectomy and modified D2 lymphadenectomy. After resection, the omentum was separated from the gastrectomy specimen distal to the gastroepiploic vessels and sent separately for pathological examination. The primary endpoint was the presence of metastases in the greater omentum. RESULTS: Of 100 included patients, five (5.0 per cent) had metastases in the greater omentum. Pathology results showed advanced tumours in all five (pT4b N1 M1, pT4b N2 M1, ypT4a N1 M1, ypT3 N2 M0, ypT3 N3 M0). The resection was microscopically non-radical at the proximal (3) or distal (2) resection margin in all of these patients. Metastases in the greater omentum correlated significantly with a microscopically non-radical resection, tumour expansion in the oesophagus or duodenum, linitis plastica or a proximal gastric tumour with diameter of at least 5 cm, stage III-IV disease and (y)pM1 category. CONCLUSION: In resectable gastric cancer, the incidence of metastases in the greater omentum is low, and when present associated with advanced disease and non radical features. Thus, omentectomy as part of a radical gastrectomy may be omitted. REGISTRATION NUMBER: NCT02050659 ( http://www.clinicaltrials.gov). PMID- 27550527 TI - Obesity and posterior spinal fat content: impact on complications in non-complex lumbar spine surgery. AB - AIM: Obesity is increasing in prevalence across the world with a potentially very significant impact in spine surgery. This study aimed to characterise this in the setting of neurosurgical spine practise at a single centre in UK. Uniquely, we assess the contribution of posterior spinal fat content to intraoperative complications. MATERIALS AND METHODS: All cases of lumbar spine surgery in 1 year were investigated. Case note review was carried out documenting patient demographics, comorbidities, operative details, complications and length of stay. Ninety-four complete datasets were compiled from 128 cases. The posterior spinal fat content was recorded from T2-weighted MRI. Body mass index (BMI) was correlated with each measure using logistic multiple regression and contingency table analysis. RESULTS: Mean BMI was 28.3 (SD: 5.2) comprising one underweight (BMI <18.5), 26 normal weight (BMI: 18.5-24.9), 32 overweight (BMI >=25), 33 obese (BMI >=30) and two morbidly obese patients (BMI >=40). BMI (coefficient: 0.03, SE: 0.01, p = 0.005) and posterior spinal fat content (coefficient: 0.01, SE: 0.005, p = 0.042) correlated significantly with increasing length of stay. Procedure (p = 0.006) and complication rate (p = 0.010) also correlated with length of stay. Neither BMI nor posterior spinal fat content had a significant effect on the incidence of perioperative complications (p = 0.932, p = 0.742), operating time (p = 0.454, p = 0.748) or blood loss (p = 0.127, p = 0.692). There were three non-operative complications in the obese and overweight groups compared with none in the normal weight group, but this was not significant. Overall complication rate was 15%. CONCLUSION: Obesity and posterior spinal fat content correlate with the length of stay in simple spine surgery. There is a non significant trend towards increased non-operative complications in overweight and obese patients, which could reach significance with larger numbers and prospective data. Excess posterior spinal fat is not associated with increased operative complications, operating time or blood loss. PMID- 27550530 TI - CT Rounds Section to Begin September 2016. PMID- 27550528 TI - Sustaining hope and life courage in patients undergoing ovarian cancer surgery - the impact of care. AB - Ovarian cancer is the leading cause of death from a gynaecological malignancy in the Western World. To explore if experiences of physical comfort influenced hope and life courage during final diagnosis and early treatment, qualitative research interviews were performed with women undergoing surgery for ovarian cancer. By applying a phenomenological-hermeneutic methodology, the findings were systematically identified, put into meaning-structures, interpreted and critically discussed. The empirical material constituted a main theme concerning "Hope and life courage are created in the interplay between body and mind," where findings dealt with personal reflections and experiences in relation to the subthemes: "Experiencing discomfort," "The impact of care" and "Comfort and hope." The women's general health condition became impacted not only by their ovarian cancer disease but also by the treatment, and it was a main finding that sufficient symptom management combined with sensitive attention of the patient sustained her hope, life courage and action competences. Surgery constitutes an essential part of sufficient cancer treatment. However, the diagnostic and pre operative phase represents an insufficiently investigated area in cancer care. Improvements are therefore vital to reduce the disease burden, and improve patients' general health and quality of life, during and after treatment. PMID- 27550531 TI - Continuing Medical Education Activity in Echocardiography August 2016. PMID- 27550533 TI - Reply. PMID- 27550532 TI - Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic atherosclerotic thrombi and ulcers. AB - We present two cases in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of atherosclerotic disease in the aorta. In one patient, it identified additional atherosclerotic ulcers as well as thrombi within them which were missed by two dimensional (2D) TEE. In both cases, the size of the large mobile atherosclerotic plaque was underestimated by 2DTEE as compared with 3DTEE. Furthermore, 3DTEE provided volume quantification of the thrombi and ulcers which is not possible by 2DTEE. The echocardiographic findings of atherosclerotic plaques were confirmed by computed tomography in one patient and by surgery in the other. PMID- 27550535 TI - "Smart" drug loaded nanoparticle delivery from a self-healing hydrogel enabled by dynamic magnesium-biopolymer chemistry. AB - We report a strategy to generate a self-healing and pH responsive hydrogel network between drug-loaded nanoparticles and natural polysaccharides via magnesium-bisphosphonate ligand interactions. The injectable drug depot disassembles in a tumor-specific environment, providing localized uptake of the nanoparticles, which is highly appreciated in drug delivery applications and manufacturing of drug-loaded biomaterials using a syringe-based deposition technique. PMID- 27550534 TI - Single-electron Spin Resonance in a Quadruple Quantum Dot. AB - Electron spins in semiconductor quantum dots are good candidates of quantum bits for quantum information processing. Basic operations of the qubit have been realized in recent years: initialization, manipulation of single spins, two qubit entanglement operations, and readout. Now it becomes crucial to demonstrate scalability of this architecture by conducting spin operations on a scaled up system. Here, we demonstrate single-electron spin resonance in a quadruple quantum dot. A few-electron quadruple quantum dot is formed within a magnetic field gradient created by a micro-magnet. We oscillate the wave functions of the electrons in the quantum dots by applying microwave voltages and this induces electron spin resonance. The resonance energies of the four quantum dots are slightly different because of the stray field created by the micro-magnet and therefore frequency-resolved addressable control of each electron spin resonance is possible. PMID- 27550536 TI - Performing (heterosexual) femininity: female agency and role in sexual life and contraceptive use - a qualitative study in Australia. AB - Women's liberation and the sexual revolution have changed the social landscape for heterosexual women in the West over the past 50 years, but exploration of women's lived experiences of contraceptive use in the context of their sexual lives is comparatively recent. We conducted 94 in-depth open-ended interviews with women of reproductive age (16-49 years) living in New South Wales, Australia. Interviews were audio-recorded, transcribed verbatim and analysed using an inductive thematic approach. Four major themes are explored here: (1) what women do and do not do: unspoken gendered assumptions; (2) focus on partner's pleasure; (3) juggling responsibilities: sex as a chore; and (4) women's sexual motivations. Findings suggest sexual double standards and gender expectations continue to pervade women's sexual and contraceptive practices. We found that women performed their femininity by focusing on enabling their male partner's pleasure, while simultaneously ignoring their own sexual desires, wishes or interests. Accompanying new-found freedoms are new-found responsibilities, as women now add managing modern contraceptives and a good sex life to their list of tasks alongside paid employment, domestic labour and childrearing. Our research findings suggest that women may derive different pleasures from sex, including what we term 'connection pleasure'. PMID- 27550537 TI - Natural products for the management of xerostomia: a randomized, double-blinded, placebo-controlled clinical trial. AB - AIM: The aim of this study was to evaluate the clinical performance of lycopene enriched virgin olive oil in spray form used to treat patients with drug-induced xerostomia, comparing this with a placebo spray. MATERIALS AND METHODS: This double-blind, randomized clinical trial included elderly subjects with drug induced xerostomia (n = 60). Resting salivary flow was measured using the draining technique. The Xerostomia Inventory (XI) was used to assess symptoms and the Oral Health Impact Profile 14 (OHIP-14) to assess patient quality of life. Evaluations were made before and after 12 weeks of product/placebo application. RESULTS: Sixty patients took part in the study. Symptoms improved among the treatment group (n = 30) after 12 weeks in the following XI domains: 'Rate the difficulty you experience in speaking because of dryness' (P = 0.03); 'Rate how much saliva is in your mouth' (P = 0.03); and 'Rate the dryness of your lips' (P = 0.04). The placebo group (n = 30) underwent improvements in: 'Rate how much saliva is in your mouth' (P = 0.02) and 'Rate the dryness of your mouth' (P = 0.01). A significant improvement (P = 0.001) in oral-related quality of life (OHIP-14) was identified in the treatment group, while no significant differences were observed in the placebo group (P > 0.05). CONCLUSION: The topical application of lycopene-enriched virgin olive oil and its placebo counterpart improved xerostomia-related symptoms significantly (but not salivary flow rate) in patients with drug-induced xerostomia. PMID- 27550538 TI - Hydrodynamic interactions enhance gelation in dispersions of colloids with short ranged attraction and long-ranged repulsion. AB - We show that discrete element simulations of colloidal gelation must account for hydrodynamic interactions between suspended particles through investigation of gelation in a dispersion of colloids interacting pair-wise via short-ranged attraction and long-ranged repulsion (SALR). These dynamic simulations juxtapose self-assembly with and without hydrodynamic interactions between the particles. The long-ranged repulsion impacts the relative rates of coagulation and compaction of colloidal aggregates pre-gel, and introduces a surprising sensitivity to the nature of hydrodynamic interactions between the suspended colloids. For such SALR dispersions, we observe a significant disparity between the percolation boundaries predicted by simulations including and neglecting long ranged hydrodynamic interactions. Additionally, we find that the percolation boundaries predicted by simulations including hydrodynamic interactions agree well with those measured experimentally. Long-ranged repulsion promotes gelation via growth of anisotropic clusters regardless of the hydrodynamic model employed. However, differences between the models, which persist far from the percolation boundary, are apparent via measurements of the fractal dimension, local bond order parameters, and the collective relaxation dynamics. Notably, the growth of elongated clusters is augmented in simulations that incorporate long-ranged hydrodynamic interactions due to the anisotropic diffusion of elongated bodies at low Reynolds numbers, which favors percolation over a transition of anisotropic clusters to their more isotropic ground states. It is only in relatively dense suspensions that a combination of hydrodynamic screening and significantly faster aggregation combine to bring the two simulation methods into agreement. These results demonstrate the necessity of long-ranged hydrodynamic forces in discrete element simulations of heterogeneous gelation at the colloidal scale. PMID- 27550539 TI - Assessing the utility of autofluorescence-based pulmonary optical endomicroscopy to predict the malignant potential of solitary pulmonary nodules in humans. AB - Solitary pulmonary nodules are common, often incidental findings on chest CT scans. The investigation of pulmonary nodules is time-consuming and often leads to protracted follow-up with ongoing radiological surveillance, however, clinical calculators that assess the risk of the nodule being malignant exist to help in the stratification of patients. Furthermore recent advances in interventional pulmonology include the ability to both navigate to nodules and also to perform autofluorescence endomicroscopy. In this study we assessed the efficacy of incorporating additional information from label-free fibre-based optical endomicrosopy of the nodule on assessing risk of malignancy. Using image analysis and machine learning approaches, we find that this information does not yield any gain in predictive performance in a cohort of patients. Further advances with pulmonary endomicroscopy will require the addition of molecular tracers to improve information from this procedure. PMID- 27550540 TI - Kremen1 regulates mechanosensory hair cell development in the mammalian cochlea and the zebrafish lateral line. AB - Here we present spatio-temporal localization of Kremen1, a transmembrane receptor, in the mammalian cochlea, and investigate its role in the formation of sensory organs in mammal and fish model organisms. We show that Kremen1 is expressed in prosensory cells during cochlear development and in supporting cells of the adult mouse cochlea. Based on this expression pattern, we investigated whether Kremen1 functions to modulate cell fate decisions in the prosensory domain of the developing cochlea. We used gain and loss-of-function experiments to show that Kremen1 is sufficient to bias cells towards supporting cell fate, and is implicated in suppression of hair cell formation. In addition to our findings in the mouse cochlea, we examined the effects of over expression and loss of Kremen1 in the zebrafish lateral line. In agreement with our mouse data, we show that over expression of Kremen1 has a negative effect on the number of mechanosensory cells that form in the zebrafish neuromasts, and that fish lacking Kremen1 protein develop more hair cells per neuromast compared to wild type fish. Collectively, these data support an inhibitory role for Kremen1 in hair cell fate specification. PMID- 27550541 TI - Judging the animacy of words: The influence of typicality and age of acquisition in a semantic decision task. AB - The age at which members of a semantic category are learned (age of acquisition), the typicality they demonstrate within their corresponding category, and the semantic domain to which they belong (living, non-living) are known to influence the speed and accuracy of lexical/semantic processing. So far, only a few studies have looked at the origin of age of acquisition and its interdependence with typicality and semantic domain within the same experimental design. Twenty adult participants performed an animacy decision task in which nouns were classified according to their semantic domain as being living or non-living. Response times were influenced by the independent main effects of each parameter: typicality, age of acquisition, semantic domain, and frequency. However, there were no interactions. The results are discussed with respect to recent models concerning the origin of age of acquisition effects. PMID- 27550542 TI - Identity and sociocultural change: Comparing young indigenous people in Chiapas who have different sociodemographic trajectories. AB - One of the most commonly used distinctions in cross-cultural studies is the one between individualism and collectivism. One of the criticisms levelled at this distinction is that it fails to incorporate the differences that may exist when comparing people from a rural context with little formal education to people from the same group who live in an urban context where formal education is the norm. Bearing in mind these sociodemographic factors, we have compared the self concepts among 104 young indigenous people in Chiapas (Mexico), having divided them into three groups: "rural-traditional," "rural-urban" and "urban." These people's self-concepts were analysed using a task that contrasts personal self concept with social self-concept and a technique in which participants draw themselves along with the things and people they consider most important to them. The results reveal significant differences between the three groups. The personal categories are given a higher value in the "urban" group while the social categories score higher in the "rural-traditional" group. Regarding the results of the indigenous self-portraits, from the content analysis of the drawings, 16 categories emerged. These findings are discussed in the light of Greenfield's theory of social change and human development. PMID- 27550543 TI - Monolithic integration of room-temperature multifunctional BaTiO3-CoFe2O4 epitaxial heterostructures on Si(001). AB - The multifunctional (ferromagnetic and ferroelectric) response at room temperature that is elusive in single phase multiferroic materials can be achieved in a proper combination of ferroelectric perovskites and ferrimagnetic spinel oxides in horizontal heterostructures. In this work, lead-free CoFe2O4/BaTiO3 bilayers are integrated with Si(001) using LaNiO3/CeO2/YSZ as a tri-layer buffer. They present structural and functional properties close to those achieved on perovskite substrates: the bilayers are fully epitaxial with extremely flat surface, and exhibit robust ferromagnetism and ferroelectricity at room temperature. PMID- 27550544 TI - Daclatasvir: A Review in Chronic Hepatitis C. AB - The hepatitis C virus (HCV) NS5A replication complex inhibitor daclatasvir (Daklinza((r))) is indicated for use in combination with sofosbuvir, with or without ribavirin, in a pangenotypic all-oral regimen. In patients with chronic HCV genotype 1 or 3 infection without cirrhosis, a 12-week regimen of daclatasvir plus sofosbuvir achieved high sustained virological response rates 12 weeks' post treatment (SVR12), regardless of prior treatment experience, according to the results of the AI444040 and ALLY-3 trials. In the ALLY-3+ trial, high SVR12 rates were achieved with a 12- or 16-week regimen of daclatasvir plus sofosbuvir and ribavirin in patients with chronic HCV genotype 3 infection and advanced fibrosis or compensated cirrhosis. A daclatasvir plus sofosbuvir-based regimen demonstrated efficacy in patients with chronic HCV genotype 1, 3 or 4 infection and advanced cirrhosis or post-transplant recurrence in the ALLY-1 trial, and in patients co-infected with HCV genotype 1, 3 or 4 and HIV-1 in the ALLY-2 trial. Results of clinical trials were supported by real-world data from early-access programmes that included high numbers of patients who would have been excluded from phase 3 trials because of advanced disease and/or concomitant medical conditions. Daclatasvir plus sofosbuvir with or without ribavirin was generally well tolerated. In conclusion, an all-oral regimen comprising daclatasvir plus sofosbuvir with or without ribavirin is an important option for use in treatment naive or treatment-experienced patients with chronic HCV genotype 1, 3 or 4 infection, including in patients with advanced liver disease, post-transplant recurrence and HIV-1 co-infection. PMID- 27550545 TI - In-beam PET at clinical proton beams with pile-up rejection. AB - Positron emission tomography (PET) is a means of imaging the beta+-activity produced by the radiation field in ion beam therapy and therefore for treatment verification. Prompt gamma-rays that are emitted during beam application challenge the detectors and electronics of PET systems, since those are designed for low and medium count rates. Typical PET detectors operated according to a modified Anger principle suffer from multiple events at high rates. Therefore, in beam PET systems using such detectors rely on a synchronization of beam status and measurement to reject deteriorated data. In this work, a method for pile-up rejection is applied to conventional Anger logic block detectors. It allows for an in-beam data acquisition without further synchronization. Though cyclotrons produce a continuous wave beam, the radiation field shaping technique introduces breaks in the application. Time regimes mimicking synchrotrons as well as cyclotron based ones using double-scattering or pencil beam scanning field shaping at dose rates of 0.5, 1.0 and 2.0Gy/min were investigated. Two types of inhomogeneous phantoms were imaged. The first one simulates cavity structures, the other one mimics a static lung irradiation. It could be shown that, depending on the dose rate and the beam time structure, in-beam measurement including a few seconds decay time only, yield images which revealed all inhomogeneities in the phantoms. This technique can be the basis for the development of an in-beam PET system with traditional detectors and off-the-shelf electronics. PMID- 27550546 TI - Low Levels of MicroRNA-21 Are a Marker of Reduced Arterial Stiffness in Well Controlled Hypertension. AB - MicroRNAs (miRNAs) play a crucial role in myocardial and vascular remodeling and have emerged as potential diagnostic and prognostic biomarkers or as therapeutic targets. The authors aimed to investigate the expression profile of selected miRNAs in the peripheral blood of patients with well-controlled essential hypertension in relation to arterial stiffness. Expression levels of miRNAs miRNA 1, miRNA-133a, miRNA-26b, miRNA-208b, miRNA-499, and miRNA-21 in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Carotid-femoral pulse wave velocity (cfPWV) and carotid radial pulse wave velocity (crPWV) were evaluated at baseline and after 1 year of effective antihypertensive therapy. A total of 95 patients (50 men, mean age 62+/ 9 years) with well-controlled essential hypertension were included in the analysis. Only miRNA-21 was independently correlated with changes in both cfPWV and crPWV, independently of blood pressure levels (r=-0.56 and r=-0.46, respectively; P<.001 for both). Low levels of miRNA-21 are strongly associated with an improvement in arterial stiffness in patients with well-controlled essential hypertension, independently of their blood pressure levels. These data highlight the significance of miRNA-21 in vascular remodeling and its role as a potential prognostic marker and future therapeutic target. PMID- 27550547 TI - Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease. AB - Increasing evidence suggests a role of intestinal dysbiosis in obesity and non alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7alpha dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G-) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID- 27550548 TI - Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis. AB - BACKGROUND Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. MATERIAL AND METHODS The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. RESULTS While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. CONCLUSIONS Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID- 27550549 TI - Effect of Vildagliptin Versus Sulfonylurea in Muslim Patients with Type 2 Diabetes Fasting During Ramadan in Egypt: Results from VIRTUE Study. AB - INTRODUCTION: Fasting in patients with type 2 diabetes mellitus (T2DM) is associated with high risk of hypoglycemia. The aim of this study was to compare the effectiveness and safety of vildagliptin in T2DM patients fasting during Ramadan in a real-life setting in Egypt. METHODS: In this 16-week prospective and noninterventional study, data were collected up to 6 weeks before and after Ramadan fasting. Patients who had received vildagliptin or sulfonylurea (SU) either as dual therapy with metformin or as monotherapy were enrolled into the study. RESULTS: Two hundred fifty four patients were enrolled in the study, out of which 246 [121 (97.6%) treated with vildagliptin and 125 (99.2%) with SU] were included in the safety analysis set. A significantly lower proportion of patients experienced >=1 hypoglycemic event (HE) with vildagliptin as compared to those receiving SUs (1.7% vs. 19.2%, respectively; p < 0.001). No patient in either group reported a grade 2 HE. At week 16, mean change in HbA1c from baseline for vildagliptin and SU were -0.1% and +0.3%, respectively, with a between-treatment difference of -0.4% (p < 0.001). Mean change in body weight from baseline for vildagliptin and SU were -0.8 and -0.1 kg, with a between-treatment difference of -0.7 kg (p = 0.011). A higher proportion of SU-treated patients experienced adverse events compared to those treated with vildagliptin (23.2% vs. 5.8%, respectively), the primary reason being the high incidence of hypoglycemia in the SU group (n = 24, 19.2%). CONCLUSIONS: Treatment with vildagliptin was associated with lower incidence of hypoglycemia compared with SU and showed good glycemic and weight control in patients with T2DM fasting during Ramadan in a real-life setting in Egypt. FUNDING: Novartis Pharma AG. PMID- 27550550 TI - Patterns and Impact of Hypoglycemia, Hyperglycemia, and Glucose Variability on Inpatients with Insulin-Treated Cystic Fibrosis-Related Diabetes. AB - INTRODUCTION: Mortality in patients with cystic fibrosis-related diabetes (CFRD) is higher than that in patients with cystic fibrosis without diabetes. Hypoglycemia, hyperglycemia, and glucose variability confer excess mortality and morbidity in the general inpatient population with diabetes. METHODS: We investigated patterns of hypoglycemia and the association of hypoglycemia, hyperglycemia, and glucose variability with mortality and readmission rate in inpatients with CFRD. All capillary blood glucose (CBG) readings (measured using the Abbott Precision web system) of patients with insulin-treated CFRD measured within our health board between January 2009 and January 2015 were. Frequency and timing of hypoglycemia (<4 mmol/L) and was recorded. The effect of dysglycemia on readmission and mortality was investigated with survival analysis. RESULTS: Sixty six patients were included. A total of 22,711 CBG results were included in the initial analysis. Hypoglycemia was common with 1433 episodes (6.3%). Hypoglycemia ascertainment was highest between 2400 and 0600 h. Hypoglycemia was associated with a significantly higher rate of readmission or death over the 3.5-year follow up period (P = 0.03). There was no significant association between hyperglycemia or glucose variability and the rate of readmission and mortality. CONCLUSION: Among inpatients with CFRD hypoglycemia is common and is associated with an increased composite endpoint of readmission and death. As with previously reported trends in general inpatient population this group shows a peak incidence of hypoglycemic during the night. PMID- 27550551 TI - Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance. AB - Cation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins' proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human. PMID- 27550553 TI - Magnetically Assembled SERS Substrates Composed of Iron-Silver Nanoparticles Obtained by Laser Ablation in Liquid. AB - The widespread application of surface-enhanced Raman scattering (SERS) would benefit from simple and scalable self-assembly procedures for the realization of plasmonic arrays with a high density of electromagnetic hot-spots. To this aim, the exploitation of iron-doped silver nanoparticles (NPs) synthesized by laser ablation of a bulk bimetallic iron-silver target immersed in ethanol is described. The use of laser ablation in liquid is key to achieving bimetallic NPs in one step with a clean surface available for functionalization with the desired thiolated molecules. These iron-silver NPs show SERS performances, a ready response to external magnetic fields and complete flexibility in surface coating. All these characteristics were used for the magnetic assembly of plasmonic arrays which served as SERS substrates for the identification of molecules of analytical interest. The magnetic assembly of NPs allowed a 28-fold increase in the SERS signal of analytes compared to not-assembled NPs. The versatility of substrate preparation and the SERS performances were investigated as a function of NPs surface coating among different thiolated ligands. These results show a simple procedure to obtain magnetically assembled regenerable plasmonic arrays for repeated SERS investigation of different samples, and it can be of inspiration for the realization of other self-assembled and reconfigurable magnetic-plasmonic devices. PMID- 27550552 TI - Cognitive Behavioral Therapy for Insomnia in Older Veterans Using Nonclinician Sleep Coaches: Randomized Controlled Trial. AB - OBJECTIVES: To test a new cognitive behavioral therapy for insomnia (CBT-I) program designed for use by nonclinicians. DESIGN: Randomized controlled trial. SETTING: Department of Veterans Affairs healthcare system. PARTICIPANTS: Community-dwelling veterans aged 60 and older who met diagnostic criteria for insomnia of 3 months duration or longer (N = 159). INTERVENTION: Nonclinician "sleep coaches" delivered a five-session manual-based CBT-I program including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy (individually or in small groups), with weekly telephone behavioral sleep medicine supervision. Controls received five sessions of general sleep education. MEASUREMENTS: Primary outcomes, including self-reported (7-day sleep diary) sleep onset latency (SOL-D), wake after sleep onset (WASO-D), total wake time (TWT-D), and sleep efficiency (SE-D); Pittsburgh Sleep Quality Index (PSQI); and objective sleep efficiency (7-day wrist actigraphy, SE-A) were measured at baseline, at the posttreatment assessment, and at 6- and 12-month follow-up. Additional measures included the Insomnia Severity Index (ISI), depressive symptoms (Patient Health Questionnaire-9 (PHQ-9)), and quality of life (Medical Outcomes Study 12-item Short-form Survey version 2 (SF-12v2)). RESULTS: Intervention subjects had greater improvement than controls between the baseline and posttreatment assessments, the baseline and 6-month assessments, and the baseline and 12-month assessments in SOL-D (-23.4, -15.8, and -17.3 minutes, respectively), TWT-D ( 68.4, -37.0, and -30.9 minutes, respectively), SE-D (10.5%, 6.7%, and 5.4%, respectively), PSQI (-3.4, -2.4, and -2.1 in total score, respectively), and ISI (-4.5, -3.9, and -2.8 in total score, respectively) (all P < .05). There were no significant differences in SE-A, PHQ-9, or SF-12v2. CONCLUSION: Manual-based CBT I delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia. PMID- 27550554 TI - Genetic mapping of QTL for the sizes of eight consecutive leaves below the tassel in maize (Zea mays L.). AB - KEY MESSAGE: A set of RIL population was used to detect QTL associated with the sizes of eight consecutive leaves, across different environments, and ten QTL clusters were identified as main QTLs. One of the important parameters of the maize leaf architecture that affects light penetration into the canopy, leaf size, has long attracted breeders' attention for optimizing the plant type of maize and for maximizing the grain yield (GY). In this study, we used 253 RIL lines derived from a cross between B73 and SICAU1212 to investigate the leaf widths (LWs), leaf lengths (LLs), and leaf areas (LAs) of eight consecutive leaves of maize below the tassel and GY across different environments and to identify quantitative traits loci (QTLs) controlling the above-mentioned traits, using inclusive interval mapping for single-environment analysis plus a mixed model-based composite interval mapping for joint analysis. A total of 171 and 159 putative QTLs were detected through these two mapping methods, respectively. Single-environment mapping revealed that 39 stable QTLs explained more than 10 % of the phenotypic variance, and 35 of the 39 QTLs were also detected by joint analysis. In addition, joint analysis showed that nine of the 159 QTLs exhibited significant QTL * environment interaction and 15 significant epistatic interactions were identified. Approximately 47.17 % of the QTLs for leaf architectural traits in joint analysis were concentrated in ten main chromosomal regions, namely, bins 1.07, 2.02, 3.06, 4.09, 5.01, 5.02, 5.03-5.04, 5.07, 6.07, and 8.05. This study should provide a basis for further fine-mapping of these main genetic regions and improvement of maize leaf architecture. PMID- 27550555 TI - Caudal analgesia and cardiothoracic surgery: a look at postoperative pain scores in a pediatric population. AB - AIM: Caudal epidural anesthesia has been shown to reduce stress response and shorten the time to extubation in children after cardiac surgery. Combined with general anesthesia, regional anesthesia has been proven to be safe and efficacious in the pediatric population. It is not known, however, whether the use of caudal anesthesia actually reduces postoperative pain scores and decreases postoperative opioid use. METHODS: We retrospectively analyzed the charts of 199 children who underwent repair for atrial septal defect (ASD), ventricular septal defect (VSD), and Tetralogy of Fallot (TOF) at a major academic children's hospital between 2010 and 2013. RESULTS: Eighty-six patients underwent preoperative placement of caudal anesthesia (bupivacaine 0.25% 1 ml.kg-1 up to 20 ml + clonidine 2mcg.kg-1 + Duramorph 40 mcg.kg-1 up to 2.5 mg) and 113 patients did not have a caudal block. Postoperative cardiac intensive care pain scores were analyzed according to standard nurse-recorded patient-appropriate pain scales ranging from 0 to 10 (CRIES for neonates and FLACC for 2 months-7 years). There was no statistical difference between caudal and noncaudal groups with respect to postoperative pain scores or with postoperative opioid requirements. There was a statistical significance with regard to intraoperative opioid use as noncaudal patients invariably received more opioid during the procedure. CONCLUSION: Although regional anesthesia reduced intraoperative opioid usage, there was no difference in postoperative opioid usage or pain scores. PMID- 27550557 TI - High-performance liquid chromatography based chemical fingerprint analysis and chemometric approaches for the identification and distinction of three endangered Panax plants in Southeast Asia. AB - Among Panax genus, only three endangered species Panax notoginseng, P. vietnamensis, and P. stipuleanatus that have a similar morphology are mainly distributed in Southeast Asia. These three plants are usually misidentified or adulterated. To identify them well, their chemical chromatographic fingerprints were established by an effective high-performance liquid chromatography method. By comparing the chromatograms, the three Panax species could be distinguished easily using the 22 characteristic peaks. Besides, the data of the chromatographic fingerprints aided by chemometric approaches were applied for the identification and investigation the relationship of different samples and species. Using similarity analysis, the chemical components revealed higher similarity between P. vietnamensis and P. stipuleanatus. The results of hierarchical clustering analysis indicated that samples belonging to the same species could be clustered together. The result of principal component analysis was similar with hierarchical clustering analysis and the three principal components accounted for >80.5% of total variability. PMID- 27550556 TI - Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study. AB - Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here, we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n = 29) and without (FHD-, n = 21) a family history of developmental dyslexia. We further controlled for socioeconomic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior/middle frontal and right fusiform gyri in FHD- compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHD- children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models. PMID- 27550559 TI - Ethical Questions about Platelet Transfusions at the End of Life. AB - This case of platelet transfusion in palliative care illustrates a common dilemma in transfusion medicine: approval of the use of a scarce, yet potentially life saving, resource. As in this case, these decisions often involve seriously ill patients with acute needs and evolving goals of care. The use of resources to treat the patient at hand must be balanced against maintaining adequate resources to treat future patients. In this setting, the ethical principles of beneficence and social justice are in conflict. PMID- 27550558 TI - Diffusion imaging of cerebral diaschisis in childhood arterial ischemic stroke. AB - BACKGROUND: Diffusion-weighted imaging magnetic resonance imaging may detect changes in brain structures remote but connected to stroke consistent with neuropathological descriptions of diaschisis. Early diffusion-weighted imaging demonstrates restriction in corticospinal pathways after arterial ischemic stroke of all ages that correlates with motor outcome. AIM/HYPOTHESIS: We hypothesized that cerebral diaschisis is measurable in childhood arterial ischemic stroke and explored associations with outcome. METHODS: This sub-study of the validation of the Pediatric NIH Stroke Scale study prospectively enrolled children with acute arterial ischemic stroke and both acute and early follow-up (5-14 days) diffusion weighted imaging. Inclusion criteria were (1) unilateral middle cerebral artery arterial ischemic stroke, (2) acute and subacute diffusion-weighted imaging (b = 1000), and (3) 12 month neurological follow-up (Pediatric Stroke Outcome Measure). A validated method using ImageJ software quantified diffusion-weighted imaging diaschisis in anatomically connected structures. Diaschisis measures were corrected for infarct volume, compared to age, imaging timing, and outcomes (Chi square/Fisher, Mann-Whitney test). RESULTS: Nineteen children (53% male, median 8.1 years) had magnetic resonance imaging at medians of 21 and 168 h post-stroke onset. Diaschisis was common and evolved over time, observed in one (5%) on acute but eight (42%) by follow-up diffusion-weighted imaging. Thalamic and callosal diaschisis were most common (5, 26%). Estimates of perilesional diaschisis varied (54 +/- 18% of infarct volume). Children with diaschisis tended to be younger (7.02 +/- 5.4 vs. 11.82 +/- 4.3 years, p = 0.08). Total diaschisis score was associated with poor cognitive outcomes (p = 0.03). Corticospinal tract diaschisis was associated with motor outcome (p = 0.004). Method reliability was excellent. CONCLUSIONS: Diffusion-weighted imaging diaschisis occurs in childhood arterial ischemic stroke. Mistaking diaschisis for new areas of infarction carries important clinical implications. Improved recognition and study are required to establish clinical relevance. PMID- 27550560 TI - Is Consent to Autopsy Necessary? Cartesian Dualism in Medicine and Its Limitations. AB - When a hospitalization ends in death, a request for an autopsy can lead to an emotionally charged encounter between a physician and the deceased patient's family. A case is presented in which a cardiac surgeon, believing he might have made a mistake, requests an autopsy, but members of the deceased patient's family believe that she would not have wanted an autopsy performed. A central question discussed in this commentary is whether and when consent for autopsy is necessary. We discuss two theoretical frameworks that support differing views on this question. Beyond engaging this philosophical discussion, we also highlight a practical approach to discussing an autopsy with a grieving family by using the case presented. PMID- 27550561 TI - I Might Have Some Bad News: Disclosing Preliminary Pathology Results. AB - Cytopathology is a subspecialty of pathology in which pathologists frequently interact directly with patients. Often this interaction is in the context of fine needle aspiration (FNA) procedures performed at the bedside by the cytopathologist or by another clinician with the cytopathologist present. Patient requests for preliminary results in such settings raise fundamental questions about professional scope of practice and communication of uncertainty that apply not merely to pathologists but to all clinicians. In certain settings, cytopathologists may share preliminary diagnostic impressions directly with patients. Essential to these conversations is the need to articulate potential uncertainty about both the diagnosis and next steps. In addition, the involvement and notification of the referring physician is obligatory, both for care coordination and to ensure that patients receive a consistent message. PMID- 27550562 TI - Requests for VIP Treatment in Pathology: Implications for Social Justice and Systems-Based Practice. AB - Preferential treatment of patients whom we deem "very important" is a practice that is common in our health care system. The impact of this designation and the care that results is rarely studied or scrutinized. Although we assume that this type of treatment results in superior outcomes, this assumption can be wrong for a variety of reasons, which we discuss here. In addition to expressing unjust preferential treatment for some patients and not others, VIP medicine could compromise patient safety. PMID- 27550563 TI - Ordering Stains That Aren't Indicated. AB - The pathologist rarely interacts with patients face-to-face, but he or she nonetheless maintains a crucial relationship with the patient (i.e., the patient pathologist relationship). A more tangible relationship, the pathologist clinician relationship, is typically augmented by the patient-pathologist relationship, but at times the two distinct relationships are at odds, creating ethical dilemmas for the pathologist. This case study and discussion highlight some of these potential ethical questions and underscore the need for pathologists and clinicians to have cooperative, collaborative, and professional relationships. Pathologists should feel empowered to guide the clinician's use of appropriate clinical testing to ensure proper management of the patient and responsible use of health care resources. PMID- 27550564 TI - Improving Pathologists' Communication Skills. AB - The 2015 Institute of Medicine report on diagnostic error has placed a national spotlight on the importance of improving communication among clinicians and between clinicians and patients [1]. The report emphasizes the critical role that communication plays in patient safety and outlines ways that pathologists can support this process. Despite recognition of communication as an essential element in patient care, pathologists currently undergo limited (if any) formal training in communication skills. To address this gap, we at the University of Washington Medical Center developed communication training with the goal of establishing best practice procedures for effective pathology communication. The course includes lectures, role playing, and simulated clinician-pathologist interactions for training and evaluation of pathology communication performance. Providing communication training can help create reliable communication pathways that anticipate and address potential barriers and errors before they happen. PMID- 27550566 TI - Pathology Image-Sharing on Social Media: Recommendations for Protecting Privacy While Motivating Education. AB - There is a rising interest in the use of social media by pathologists. However, the use of pathology images on social media has been debated, particularly gross examination, autopsy, and dermatologic condition photographs. The immediacy of the interactions, increased interest from patients and patient groups, and fewer barriers to public discussion raise additional considerations to ensure patient privacy is protected. Yet these very features all add to the power of social media for educating other physicians and the nonmedical public about disease and for creating better understanding of the important role of pathologists in patient care. The professional and societal benefits are overwhelmingly positive, and we believe the potential for harm is minimal provided common sense and routine patient privacy principles are utilized. We lay out ethical and practical guidelines for pathologists who use social media professionally. PMID- 27550565 TI - Error Disclosure in Pathology and Laboratory Medicine: A Review of the Literature. AB - Since the 1990s, the fields of anatomic and clinical pathology have made strong commitments to improving patient safety, including the creation of formal and informal guidelines for assessing and reporting quality lapses. Unfortunately, some medical errors are inevitable. Patient safety experts advocate full and complete disclosure of all serious medical errors in an effort to preserve the patient-physician relationship and minimize the risk of harm to patients. While evidence suggests that most pathologists disclose serious medical errors, many do not disclose such errors to patients. A literature review of articles published on diagnostic error disclosure in pathology and laboratory medicine suggests that there are in fact persistent barriers to the disclosure of diagnostic errors that are specific to pathology. A number of these barriers are considered here, followed by recommendations for improving patient safety in pathology. PMID- 27550567 TI - Ethical Considerations about EHR-Mediated Results Disclosure and Pathology Information Presented via Patient Portals. AB - Electronic health records (EHR) now include patient portals where patients can obtain clinical reports, including notes, radiology reports, and laboratory/anatomic pathology results. Although portals increase patient access to information, no guidelines have been developed for hospitals about appropriate delays in posting different types of pathology reports to the EHR. Delays exist as a matter of policy to allow physicians time to answer questions and provide emotional support when discussing sensitive results with patients. Some types of results are more sensitive than others, however, including results of cancer, genetic, and HIV testing. Ethical questions about patient access to test results online are discussed. PMID- 27550568 TI - The Penetrating Gaze and the Decline of the Autopsy. AB - Understanding the decline in the autopsy rate can be furthered through analysis of Foucault's idea of the medical gaze and the ancient Greek idea of theoria. The medical gaze has shifted over time from the surface of the body to the inner organs to the cellular and subcellular levels. Physicians and loved ones of the deceased person are not likely to "gaze" at the same levels. Patients' loved ones might not theorize as physicians do; they have different interests, which suggest the need for more attention to informed consent for autopsies. Responding to this need should take priority over efforts to increase the autopsy rate, and it can also be seen as an opportunity to improve autopsy and autopsy consent practices. PMID- 27550569 TI - Public Figures, Professional Ethics, and the Media. AB - Death certificates and autopsy reports contain personal identifying information and clinical information protected under the Health Insurance Portability and Accountability Act (HIPAA) of 1996. These documents are used, for example, by the families of the deceased for settling estates, bereavement and closure, and genetic counseling of relatives. Insurance companies, public health and law enforcement officials, and the legal community also have legitimate claims to this information. Critical ethical questions have not yet been settled about whether and when this information should be public and under which circumstances making this kind of information public incurs benefits, harms, or both. Additional considerations include which organizations-the media, academic institutions, or government agencies, for example-are best suited to interpret these questions and respond to them. PMID- 27550570 TI - The Use of Visual Arts as a Window to Diagnosing Medical Pathologies. AB - Observation is a key step preceding diagnosis, prognostication, and treatment. Careful patient observation is a skill that is learned but rarely explicitly taught. Furthermore, proper clinical observation requires more than a glance; it requires attention to detail. In medical school, the art of learning to look can be taught using the medical humanities and especially visual arts such as paintings and film. Research shows that such training improves not only observation skills but also teamwork, listening skills, and reflective and analytical thinking. Overall, the use of visual arts in medical school curricula can build visual literacy: the capacity to identify and analyze facial features, emotions, and general bodily presentations, including contextual features such as clothing, hair, and body art. With the ability to formulate and convey a detailed "picture" of the patient, clinicians can integrate aesthetic and clinical knowledge, helping facilitate the diagnosing of medical pathologies. PMID- 27550572 TI - Decoupling strain and ligand effects in ternary nanoparticles for improved ORR electrocatalysis. AB - Ternary Pt-Au-M (M = 3d transition metal) nanoparticles show reduced OH adsorption energies and improved activity for the oxygen reduction reaction (ORR) compared to pure Pt nanoparticles, as obtained by density functional theory. The strain and ligand effects in nanoparticles are decoupled and correlated with the extended Pt(111) surface for benchmarking. The ternary metal in the core allows for tuning the catalytic activity through strain effects. Pt-Au-M for M = Cr, Mn, Co, Cu, Zn nanoparticles are of particular interest as they exhibit an optimal contribution of strain, ligand effects and stability. Good agreement is found with experimental studies showing increased activity of Pt-Au-Fe/Ni nanoparticles, and mid to late 3d transition metals are predicted to exhibit enhance activity and stability with respect to pure Pt nanoparticles. PMID- 27550573 TI - Correlation of autoantibodies against BP180/BP230 in response to topical corticosteroids in patients with bullous pemphigoid. AB - Topical steroids are effective in treating bullous pemphigoid (BP). Autoantibodies against BP180 are related to disease activity, but correlation of these autoantibodies with response to topical steroid therapy has not yet been clearly evaluated. We investigate the usefulness of close and early monitoring of autoantibodies against BP180 and BP230 for assessment of response to therapy and early detection of therapeutic failure in BP patients treated topically. In eight BP patients under treatment with topical or systemic steroid therapy we retrospectively evaluated clinical course and autoantibodies against BP180 and BP230 as well as indirect immunofluorescence titres (IIF). Data were included at diagnosis, during hospitalization and follow-ups. Autoantibodies against BP180 parallel disease activity in all topically and as well as systemically treated patients. Autoantibodies against BP230 correlated in five out of eight patients. Autoantibodies directed against BP180 and, to a lesser degree, against BP230 correlate with the clinical course of topically treated BP patients. Monitoring autoantibodies against BP180 is a useful tool to evaluate the efficacy of topical therapy in BP. PMID- 27550575 TI - Confounding effects of spatial variation on shifts in phenology. AB - Shifts in the timing of life history events have become an important source of information about how organisms are responding to climate change. Phenological data have generally been treated as purely temporal, with scant attention to the inherent spatial aspects of such data. However, phenological data are tied to a specific location, and considerations of sampling design, both over space and through time, can critically affect the patterns that emerge. Focusing on flowering phenology, we describe how purely spatial shifts, such as adding new study plots, or the colonization of a study plot by a new species, can masquerade as temporal shifts. Such shifts can look like responses to climate change but are not. Furthermore, the same aggregate phenological curves can be composed of individuals with either very different or very similar phenologies. We conclude with a set of recommendations to avoid ambiguities arising from the spatiotemporal duality of phenological data. PMID- 27550574 TI - Potential biocontrol actinobacteria: Rhizospheric isolates from the Argentine Pampas lowlands legumes. AB - Control of fungal plant diseases by using naturally occurring non-pathogenic microorganisms represents a promising approach to biocontrol agents. This study reports the isolation, characterization, and fungal antagonistic activity of actinobacteria from forage soils in the Flooding Pampa, Argentina. A total of 32 saprophytic strains of actinobacteria were obtained by different isolation methods from rhizospheric soil of Lotus tenuis growing in the Salado River Basin. Based on physiological traits, eight isolates were selected for their biocontrol related activities such as production of lytic extracellular enzymes, siderophores, hydrogen cyanide (HCN), and antagonistic activity against Cercospora sojina, Macrophomia phaseolina, Phomopsis sp., Fusarium oxysporum, and Fusarium verticilloides. These actinobacteria strains were characterized morphologically, physiologically, and identified by using molecular techniques. The characterization of biocontrol-related activities in vitro showed positive results for exoprotease, phospholipase, fungal growth inhibition, and siderophore production. However, none of the strains was positive for the production of hydrogen cyanide (HCN). Streptomyces sp. MM140 presented the highest index for biocontrol, and appear to be promising pathogenic fungi biocontrol agents. These results show the potential capacity of actinobacteria isolated from forage soils in the Argentine Pampas lowlands as promising biocontrol agents, and their future agronomic applications. PMID- 27550571 TI - Dermatological adverse events with taxane chemotherapy. AB - Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel. PMID- 27550576 TI - Risk factors for candidaemia in critically ill patients in intensive care units as compared to internal medicine wards. PMID- 27550614 TI - A cross-jurisdictional evaluation of insurance coverage among HIV care patients following the Affordable Care Act. AB - The impact of the Affordable Care Act (ACA) on HIV care patients, aged 18-64, was evaluated in three jurisdictions with Medicaid expansion (Chicago, New York State, and Washington) and three jurisdictions without Medicaid expansion (Georgia, Texas, and Virginia) using data from the Medical Monitoring Project. Multivariate regression models were used to evaluate insurance status that was reported pre- and post-ACA; self-reported impact of ACA on HIV care was explored with descriptive statistics. The likelihood of having insurance was significantly greater post-ACA compared to pre-ACA in Chicago (aRR = 1.33, 95%CI = 1.20, 1.47), Washington (aRR = 1.15, 95%CI = 1.08, 1.22), and Virginia (aRR = 1.14, 95%CI = 1.00, 1.29). In Washington and Chicago, the likelihood of being Medicaid-insured was greater post-ACA compared to pre-ACA implementation (Chicago: aRR = 1.25, 95%CI = 1.03,1.53; Washington: aRR = 1.66 95% CI = 1.30, 2.13). No other significant differences were observed. Only a subset of HIV care patients (range: 15-35%) reported a change in insurance that would have coincided with the implementation of ACA; and within this subset, a change in medical care costs was the most commonly noted issue. In conclusion, the influence of ACA on insurance coverage and other factors affecting HIV care likely varies by jurisdiction. PMID- 27550615 TI - Cholinergic System and Neuroinflammation: Implication in Multiple Sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) characterized by leucocytes infiltration, demyelination, axonal degeneration and neuronal death. Although the etiology of MS is still unkwon, inflammation and autoimmunity are considered to be key players of the disease. Nervous System: The severe alterations affecting the nervous system contribute to the motor and cognitive disabilities and are in large part dependent on severe inflammatory processes active in both central nervous system and immune system. Acetylcholine (ACh) appears to be involved in the modulation of central and peripheral inflammation. Immune cells as well as astrocytes and microglia respond to ACh stimuli by activation of cholinergic receptors. Muscarinic and nicotinic receptors differently contribute to the modulation of immunological and inflammatory processes stimulating pro- and anti inflammatory cytokines respectively. The role played by ACh in MS is not yet fully understood, although some results point to its involvement in different neurological disorders such as Alzheimer's disease and schizophrenia. CONCLUSION: In the present review we summarize the evidence indicating the correlation between nervous system dysfunction in MS, with inflammation and cholinergic system alterations. Experiments performed in MS animal models and analyses on biological fluids from MS patients such as blood, serum and cerebrospinal fluid suggest that cholinergic alterations may contribute to the dysregulated inflammatory processes of MS. Many current therapeutic approaches in MS are based on anti-inflammatory drugs. We also discuss how the use of cholinesterase inhibitors or ACh mimetics may represent a new interesting therapeutic approach in MS. PMID- 27550616 TI - On the complex structural diffusion of proton holes in nanoconfined alkaline solutions within slit pores. AB - The hydroxide anion OH(-)(aq) in homogeneous bulk water, that is, the solvated proton hole, is known to feature peculiar properties compared with excess protons solvated therein. In this work, it is disclosed that nanoconfinement of such alkaline aqueous solutions strongly affects the key structural and dynamical properties of OH(-)(aq) compared with the bulk limit. The combined effect of the preferred hypercoordinated solvation pattern of OH(-)(aq), its preferred perpendicular orientation relative to the confining surfaces, the pronounced layering of nanoconfined water and the topology of the hydrogen bond network required for proton hole transfer lead to major changes of the charge transport mechanism, in such a way that the proton hole migration mechanism depends exquisitely on the width of the confined space that hosts the water film. Moreover, the anionic Zundel complex, which is of transient nature in homogeneous bulk solutions, can be dynamically trapped as a shallow intermediate species by suitable nanoconfinement conditions. PMID- 27550617 TI - Invasive Scalp Melanoma: Role for Enhanced Detection Through Professional Training. AB - BACKGROUND: Scalp and neck melanomas (SNMs) have a relatively poor prognosis compared to other sites, and represent an anatomically challenging area for detection. The aim of this study was to identify the role of the hairdresser in detection of SNMs. METHODS: A tertiary surgical oncology institutional database was retrospectively reviewed for all patients undergoing resection of a scalp, posterior neck, or retro auricular invasive primary melanoma between 2008 and 2014. RESULTS: SNMs accounted for 128 melanoma patients during the study period, with median age 66 years, 88 % male, and median Breslow thickness 1.55 mm. Hairdressers detected 10 % of all SNMs, with hairdresser-detected SNMs presenting 13 years younger (53 vs. 66 years, P = 0.015), and with a trend towards lower Breslow depth (1.15 vs. 1.63) and more frequent discovery in AJCC Stage Ia or Ib (66.7 % vs. 44.8 %) than otherwise-detected SNMs. Women with SNMs were 1.8-fold more likely than men to have their SNMs detected by a hairdresser (P = 0.001), and presented at higher AJCC clinical stage than men and required wider surgical resection margins (P = 0.011). Women with hairdresser-detected SNMs were younger, with lower Breslow thickness and lower AJCC Clinical Stage than women with otherwise-detected SNM. CONCLUSION: This study suggests that hairdressers play a critical role in detection of invasive primary scalp and neck melanoma, accounting for 10 % of all melanomas referred to a tertiary surgical oncology center. Quality improvement initiatives aimed at increasing early detection of scalp and neck melanoma should include members of the cosmetology community. PMID- 27550618 TI - A Safe Method for Middle Colic Dissection and Ligation at its Origin in a Laparoscopic Extended Right Hemicolectomy. AB - BACKGROUND: Laparoscopic extended right hemicolectomy is regarded as one of the more difficult procedures in colorectal surgery due to the complexity of the dissection around the pancreatic neck to identify the origin of the middle colic artery.1 Proper identification and ligation of the middle colic artery at its origin is paramount to achieve complete mesocolic excision.2 , 3 We describe our technique of middle colic vessels dissection in a laparoscopic extended right hemicolectomy. METHODS: Our patient was a 58-year-old female with a stenosing transverse colon adenocarcinoma. The video highlights the key steps of a laparoscopic extended right hemicolectomy with special attention to the dissection and identification of the origin of the middle colic vessels at the pancreatic neck. We utilized a posterior-to-anterior approach for the dissection around the superior mesenteric pedicle. RESULTS: By carefully skeletonizing the pancreas from the body to the neck, the superior mesentery pedicle is isolated and skeletonized to identify the origin of the middle colic vessels. A posterior to-anterior approach is used to complete the skeletonisation before ligation of the middle colic vessels at its origin. Operative time was 288 min with an estimated blood loss of 40 ml. The patient recovered well without complications of pancreatitis and was discharged on postoperative day 5. Histology revealed a 4 cm moderately differentiated adenocarcinoma with 10 of 34 lymph nodes involved pT3N2b. CONCLUSIONS: With the increasing popularity of laparoscopic surgery, meticulous laparoscopic dissection of the middle colic vessels is feasible and safe and may potentially help to optimize oncological outcomes for laparoscopic extended right hemicolectomy. PMID- 27550619 TI - Effects of a Health and Social Collaborative Case Management Model on Health Outcomes of Family Caregivers of Frail Older Adults: Preliminary Data from a Pilot Randomized Controlled Trial. AB - Family caregiving is an important form of informal care provided to frail, community-dwelling older adults. This article describes a health and social collaborative case management (HSC-CM) model that aims to optimize the support given to caregivers of frail elderly adults. The model was characterized by a comprehensive assessment to identify the caregiver's needs; a case management approach to provide integrated, coordinated, continued care; and multidisciplinary group-based education customized to the caregiver's individualized needs. A pilot study using a randomized controlled trial study design was conducted to evaluate the effects of the HSC-CM on caregiver burden and health-related quality of life of family caregivers of frail elderly adults. Sixty family caregivers (mean age 61.3 +/- 15.5) of frail older adults recruited from a community center for elderly adults in Hong Kong were randomly assigned to receive a 16-week HSC-CM intervention or usual care. Case managers who conducted a comprehensive assessment of the care dyads to identify caregiver needs using a case management approach to optimize care coordination and continuity led the HSC CM. These case managers served as liaisons for multidisciplinary efforts to provide group-based education according to caregiver needs. Family caregivers who participated in the HSC-CM had significantly greater improvement on the Caregiver Burden Index (p = .03) and on the Medical Outcomes Study 36-item Short-Form Survey subscales, including vitality (p = .049), social role functioning (p = .047), and general well-being (p = .049). This study provides preliminary evidence indicating that client-centered care, a case management approach, and multidisciplinary support are crucial to an effective caregiving support initiative. A full-scale study is required to validate these findings. PMID- 27550620 TI - Chemodiversity of Ladder-Frame Prymnesin Polyethers in Prymnesium parvum. AB - Blooms of the microalga Prymnesium parvum cause devastating fish kills worldwide, which are suspected to be caused by the supersized ladder-frame polyether toxins prymnesin-1 and -2. These toxins have, however, only been detected from P. parvum in rare cases since they were originally described two decades ago. Here, we report the isolation and characterization of a novel B-type prymnesin, based on extensive analysis of 2D- and 3D-NMR data of natural as well as 90% (13)C enriched material. B-type prymnesins lack a complete 1,6-dioxadecalin core unit, which is replaced by a short acyclic C2 linkage compared to the structure of the original prymnesins. Comparison of the bioactivity of prymnesin-2 with prymnesin B1 in an RTgill-W1 cell line assay identified both compounds as toxic in the low nanomolar range. Chemical investigations by liquid chromatography high-resolution mass spectrometry (LC-HRMS) of 10 strains of P. parvum collected worldwide showed that only one strain produced the original prymnesin-1 and -2, whereas four strains produced the novel B-type prymnesin. In total 13 further prymnesin analogues differing in their core backbone and chlorination and glycosylation patterns could be tentatively detected by LC-MS/HRMS, including a likely C-type prymnesin in five strains. Altogether, our work indicates that evolution of prymnesins has yielded a diverse family of fish-killing toxins that occurs around the globe and has significant ecological and economic impact. PMID- 27550621 TI - Gut complex carbohydrates and intestinal microflora in broiler chickens fed with oregano (Origanum vulgare L.) aqueous extract and vitamin E. AB - One hundred and seventy one-day-old female broiler chicks were randomly divided into three groups fed with different dietary treatments: basal control diet (C); C supplemented (2 g/kg) with an oregano aqueous extract (O); C supplemented (150 mg/kg) with vitamin E (E). Growth performance was evaluated at 21 (T1) and 42 days (T2). On the same days, morphological, histochemical and microbiological analyses were performed. The O group showed the highest (p < 0.01) body weight at T1, while no differences were observed at T2. Light microscopic observation and conventional histochemistry showed no differences with regard to the two sampling times, whereas significant differences emerged among the treatments. The O treatment generally enhanced goblet cell reactivity more than both the C and E treatments. Coliform count was lower in the ileum tract of the O group at both T1 and T2 (p < 0.05) and increased with age in all groups. Escherichia coli showed the lowest values in the caecum of the O group (p < 0.001) at both sampling times. Enterococci, lactobacilli and staphylococci populations showed no differences among the different experimental groups in the caecum. In the ileum, the O group did not exhibit the sharp decline (p < 0.001) in the lactic acid bacteria population observed in the other two experimental groups. In conclusion, oregano aqueous extract supplementation seemed to elicit the best response among treatments, enabling better growth performance, enhancing both the quantity and quality of glycoconjugates involved in indirect defence actions and significantly reducing both the coliform and E. coli counts. PMID- 27550623 TI - Measurement of interleukin-6 (IL-6) and erythropoietin (EPO) in umbilical cords of preterm infants with intraventricular hemorrhage in two hospitals in Tehran. AB - BACKGROUND: Intraventricular hemorrhage (IVH) is an important cause of death in premature infants. This study aimed to assess the association of the umbilical cord plasma levels of interleukin-6 (IL-6) and erythropoietin (EPO) with the occurrence and severity of IVH in premature infants. METHODS: Fifty premature newborns of mothers with chorioamnionitis risk factor were selected via nonprobability sampling. The concentration of the cord plasma's IL-6 and erythropoietin were measured by enzyme-linked immunosorbent assay (ELISA) for 3 days. Finally, all samples underwent sonography for the diagnosis of IVH. Results analyzed statistically. RESULTS: Among the samples, 68.98% of them were diagnosed with IVH grade 1. The most severe IVH cases were detected on the second day. The mean and standard deviation of IL-6 level was 74.71 +/- 50.53 in the case group and 24.10 +/- 46.10 in the control group. There was a correlation between IL-6 levels and IVH (p = 0.0005). The mean and standard deviation of EPO level was 18.38 +/- 15.23 in the IVH group and 6.45 +/- 13.48 in samples without IVH. A correlation was detected between EPO level and IVH (p = 0.005). CONCLUSION: The concentration of IL-6 and EPO levels of the cord plasma was higher in the premature newborns with IVH. PMID- 27550622 TI - Dietary choline and betaine; associations with subclinical markers of cardiovascular disease risk and incidence of CVD, coronary heart disease and stroke: the Jackson Heart Study. AB - PURPOSE: Several mechanisms have been described through which dietary intake of choline and its derivative betaine may be associated in both directions with subclinical atherosclerosis. We assessed the association of dietary intake of choline and betaine with cardiovascular risk and markers of subclinical cardiovascular disease. METHODS: Data from 3924 Jackson Heart Study (JHS) African American participants with complete food frequency questionnaire at baseline and follow-up measurements of heart disease measures were used. Multivariable linear regression models were employed to assess associations between choline and betaine intake with carotid intima-media thickness, coronary artery calcium, abdominal aortic calcium and left ventricular mass. Cox proportional hazards regression models were used to estimate associations with time to incident coronary heart disease (CHD), ischemic stroke and cardiovascular disease (CVD). RESULTS: During an average nine years of follow-up, 124 incident CHD events, 75 incident stroke events and 153 incident CVD events were documented. In women, greater choline intake was associated with lower left ventricular mass (p = 0.0006 for trend across choline quartiles) and with abdominal aortic calcium score. Among all JHS participants, there was a statistically significant inverse association between dietary choline intake and incident stroke, beta = -0.33 (p = 0.04). Betaine intake was associated with greater risk of incident CHD when comparing the third quartile of intake with the lowest quartile of intake (HR 1.89, 95 % CI 1.14, 3.15). CONCLUSIONS: Among our African-American participants, higher dietary choline intake was associated with a lower risk of incident ischemic stroke, and thus putative dietary benefits. Higher dietary betaine intake was associated with a nonlinear higher risk of incident CHD. PMID- 27550624 TI - Long-term survival of patients undergoing liver resection for very large hepatocellular carcinomas. AB - BACKGROUND: This study aimed to assess long-term survival after liver resection for huge hepatocellular carcinoma (HCC). METHODS: Patients with stage I-III HCC who underwent hepatectomy from 2002 to 2010 were identified retrospectively from prospective national databases and followed until December 2012. Patients were assigned into four groups according to tumour size: less than 3.0 cm (small), 3.0 4.9 cm (medium), 5.0-10.0 cm (large) and over 10.0 cm (huge). The primary endpoint was overall survival. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. RESULTS: A total of 11 079 patients with HCC (mean(s.d.) age 59.7 (12.0) years) were eligible for this study. Median follow-up was 72.5 months. Patients with huge HCC had the worst prognosis; overall survival rates for patients with small, medium, large and huge HCC were 72.0, 62.1, 50.8 and 35.0 per cent respectively at 5 years, and 52.6, 41.8, 35.8 and less than 20.0 per cent at 10 years (P < 0.001). Multivariable analysis showed that tumour size affected long-term survival (hazard ratio (HR) 1.31, 1.55 and 2.38 for medium, large and huge HCC respectively versus small HCC). Prognostic factors for huge HCC were surgical margin larger than 0.2 cm (HR 0.70; P = 0.025), poor differentiation (HR 1.34; P = 0.004), multiple tumours (HR 1.64; P < 0.001), vascular invasion (HR 1.52; P = 0.008), cirrhosis (HR 1.37; P = 0.013) and the use of nucleoside analogues (HR 0.69; P = 0.004). CONCLUSION: Huge HCCs have a worse prognosis than smaller HCCs after liver resection. A wide resection margin and antiviral therapy with nucleoside analogues may be associated with favourable long-term survival. PMID- 27550625 TI - Longitudinal associations between micronutrient consumption and leukocyte telomere length. AB - BACKGROUND: There are few studies on the association between nutrient intake and telomere length, which may reflect cumulative oxidative stress and indicate biological ageing. In the present study, we evaluated longitudinal associations between the consumption of micronutrients, including antioxidant nutrients and B vitamins involved in one-carbon transfer pathways, and leukocyte telomere length (LTL). METHODS: The study included 1958 middle-aged and older Korean men and women (age range at baseline: 40-69 years) from a population-based cohort. We collected dietary information at baseline using a semiquantitative food frequency questionnaire (June 2001 to January 2003) and assessed the consumption of micronutrients, including vitamins A, B1 , B2 , B3 , B6 , B9 (folate), C and E, as well as calcium, phosphorus, potassium, iron and zinc. We measured LTL using a real-time polymerase chain reaction at the 10-year follow-up examination (February 2011 to November 2012). RESULTS: In the multiple regression model adjusted for potential confounders, LTL was positively associated with the consumption of vitamin C (P < 0.05), folate (P = 0.05) and potassium (P = 0.05) in all participants. In the age-stratified analysis, the association between the consumption of vitamin C (P < 0.01), folate (P < 0.05) and potassium (P < 0.05) with LTL was significant only among participants aged <50 years. CONCLUSIONS: Our findings suggest that the earlier consumption of vitamin C, folate and potassium, which are abundant in fruits and vegetables, can delay biological ageing in middle-aged and older adults. PMID- 27550626 TI - Using Integrative Data Analysis to Examine Changes in Alcohol Use and Changes in Sexual Risk Behavior Across Four Samples of STI Clinic Patients. AB - BACKGROUND: Patients in sexually transmitted infection (STI) clinics report high levels of alcohol use, which are associated with risky sexual behavior. However, no studies have examined how changes in alcohol use relate to changes in sexual risk behavior. PURPOSE: We used parallel process latent growth modeling to explore how changes in alcohol use related to changes in sexual behavior across four samples of clinic patients. METHODS: Patients participating in HIV prevention trials from urban clinics in the Northeastern and Midwestern USA (N = 3761, 59 % male, 72 % Black) completed measures at 3-month intervals over 9-12 months. Integrative data analysis was used to create composite measures of alcohol use across samples. Sexual risk measures were counts of partners and unprotected sex acts. Parallel process models tested whether alcohol use changes were correlated with changes in the number of partners and unprotected sex. RESULTS: Growth models with good fit showed decreases that slowed over time in sexual risk behaviors and alcohol use. Parallel process models showed positive correlations between levels of (rs = 0.17-0.40, ps < 0.001) and changes in (rs = 0.21-0.80, ps < 0.05) alcohol use and number of sexual partners across studies. There were strong associations between levels of (rs = 0.25-0.43, ps < 0.001) and changes in (rs = 0.24-0.57, ps < 0.01) alcohol use and unprotected sex in one study recruiting hazardous drinkers. CONCLUSIONS: Across four samples of clinic patients, reductions in alcohol use were associated with reductions in the number of sexual partners. HIV prevention interventions may be strengthened by addressing alcohol use. PMID- 27550627 TI - Epileptic seizures in anaplastic gangliogliomas. AB - AIM: Prevalence and predictors of epileptic seizures are unknown in the malignant variant of ganglioglioma. METHODS: In a retrospective exploratory dataset of 18 supratentorial anaplastic World Health Organization grade III gangliogliomas, we studied: (i) the prevalence and predictors of epileptic seizures at diagnosis; (ii) the evolution of seizures during tumor evolution; (iii) seizure control rates and predictors of epilepsy control after oncological treatments. RESULTS: Epileptic seizures prevalence progresses throughout the natural course of anaplastic gangliogliomas: 44% at imaging discovery, 67% at histopathological diagnosis, 69% following oncological treatment, 86% at tumor progression, and 100% at the end-of-life phase. The medical control of seizures and their refractory status worsened during the tumor's natural course: 25% of uncontrolled seizures at histopathological diagnosis, 40% following oncological treatment, 45.5% at tumor progression, and 45.5% at the end-of-life phase. Predictors of seizures at diagnosis appeared related to the tumor location (i.e. temporal and/or cortical involvement). Prognostic parameters of seizure control after first-line oncological treatment were temporal tumor location, eosinophilic granular bodies, TP53 mutation, and extent of resection. Prognostic parameters of seizure control at tumor progression were a history of epileptic seizures at diagnosis, seizure control after first-line oncological treatment, eosinophilic granular bodies, and TP53 mutation. CONCLUSION: Epileptic seizures are frequently observed in anaplastic gangliogliomas and both prevalence and medically refractory status worsen during the tumor's natural course. Both oncological and antiepileptic treatments should be employed to improve the control of epileptic seizures and the quality of life of patients harboring an anaplastic ganglioglioma. PMID- 27550628 TI - Framing moving and handling as a complex healthcare intervention within the acute care of older people with osteoporosis: a qualitative study. AB - AIMS AND OBJECTIVES: To investigate healthcare staff's views and experiences of caring for older hospitalised adults (aged 60+) with osteoporosis focusing on moving and handling. Specific objectives were to explore the composition of manual handling risk assessments and interventions in osteoporosis. BACKGROUND: Osteoporosis is a skeletal disease that reduces bone density and causes increased fracture risk. Incidence rises with age and osteoporotic fractures cause increased morbidity and mortality. It is a major global health problem. In the UK older hospitalised adults are normally screened for falls risk but not necessarily for osteoporosis. As presentation of osteoporosis is normally silent until fractures are evident, it is frequently undiagnosed. Healthcare staff's knowledge of osteoporosis is often suboptimal and specific manual handling implications are under-researched. DESIGN: An exploratory qualitative content analysis research design informed by critical realism. METHODS: The purposive sample comprised 26 nursing and allied health professionals. Semi-structured interviews addressed topics including knowledge of osteoporosis, implications for acute care, moving and handling and clinical guidelines. Qualitative content data analysis was used. RESULTS: Awareness of osteoporosis prevalence in older populations varies and implications for nursing are indistinct to nonspecialists. In-hospital fractures potentially linked to suboptimal moving and handling seemed rare, but prospective studies are needed. Categories of 'Understanding moving and handling as routine care or as a healthcare intervention', with further categories 'healthcare practitioners' capacities and capabilities for dealing with people with osteoporosis' and 'the structural and organisational context for moving and handling' are reported alongside safety, frailty and dependency dimensions. CONCLUSIONS: This study informs moving and handling in higher risk groups such as osteoporosis. Clinical knowledge/expertise is required when adapting generic manual handling guidelines to specific patients/contexts. Patients' experiences of moving and handling have received limited attention. RELEVANCE TO CLINICAL PRACTICE: Increased focus on musculoskeletal conditions and moving and handling implications is required. PMID- 27550629 TI - Researching Complex and Multi-Level Workplace Factors Affecting Disability and Prolonged Sickness Absence. AB - Purpose There is growing research evidence that workplace factors influence disability outcomes, but these variables reflect a variety of stakeholder perspectives, measurement tools, and methodologies. The goal of this article is to summarize existing research of workplace factors in relation to disability, compare this with employer discourse in the grey literature, and recommend future research priorities. Methods The authors participated in a year-long collaboration that ultimately led to an invited 3-day conference, "Improving Research of Employer Practices to Prevent Disability, held October 14-16, 2015, in Hopkinton, Massachusetts, USA. The collaboration included a topical review of the literature, group conference calls to identify key areas and challenges, drafting of initial documents, review of industry publications, and a conference presentation that included feedback from peer researchers and a question/answer session with a special panel of knowledge experts with direct employer experience. Results Predominant factors in the scientific literature were categorized as physical or psychosocial job demands, work organization and support, and workplace beliefs and attitudes. Employees experiencing musculoskeletal disorders in large organizations were the most frequently studied population. Research varied with respect to the basic unit of assessment (e.g., worker, supervisor, policy level) and whether assessments should be based on worker perceptions, written policies, or observable practices. The grey literature suggested that employers focus primarily on defining roles and responsibilities, standardizing management tools and procedures, being prompt and proactive, and attending to the individualized needs of workers. Industry publications reflected a high reliance of employers on a strict biomedical model in contrast to the more psychosocial framework that appears to guide research designs. Conclusion Assessing workplace factors at multiple levels, within small and medium-sized organizations, and at a more granular level may help to clarify generalizable concepts of organizational support that can be translated to specific employer strategies involving personnel, tools, and practices. PMID- 27550630 TI - Normal myocardial strain values using 2D speckle tracking echocardiography in healthy adults aged 20 to 72 years. AB - AIMS: Evaluation of left ventricular (LV) myocardial deformation by speckle tracking echocardiography (STE) is useful for clinical and research purposes. However, strain measurements depend on the used software. Normative data for QLAB 10 (Philips) are scarce. Additionally, little is known about the influence of anthropometric factors. We aimed to establish normal adult STE-derived strain and strain rate values and to evaluate associations with anthropometrics. METHODS: One hundred fifty-five healthy subjects aged 20 to 72 years (>=28 subjects per decile) were prospectively gathered and examined with electrocardiography and two dimensional echocardiography. With STE, we assessed peak systolic LV global longitudinal strain (GLS), segmental longitudinal strain, and strain rate from the three standard apical views. RESULTS: We included 147 healthy subjects (age 44.6+/-13.7 years, 50% female, GLS -20.8+/-2.0%). Men had significantly lower GLS than women (-20.1+/-1.8% vs -21.5+/-2.0%, P<.001). GLS was significantly lower in subjects with age above 55 years (P=.029), higher blood pressure (P<.001), higher body surface area (BSA, P<.001), larger LV end-systolic and end-diastolic volumes (both P<.001), lower LV ejection fraction (P<.001), and some indices of diastolic function. After multivariable regression analysis, the correlation with systolic blood pressure, E-wave, and LV end-systolic volume remained significant. The systolic strain rates of most segments correlated with BSA. CONCLUSIONS: Our study resulted in normative LV GLS values assessed with QLAB 10. Male sex, higher BSA, and higher blood pressure negatively influence GLS. Therefore, these factors should be taken into account for strain interpretation in clinical practice. PMID- 27550631 TI - One-Pot Synthesis of Fe(III)-Polydopamine Complex Nanospheres: Morphological Evolution, Mechanism, and Application of the Carbonized Hybrid Nanospheres in Catalysis and Zn-Air Battery. AB - We report one-pot synthesis of Fe(III)-polydopamine (PDA) complex nanospheres, their structures, morphology evolution, and underlying mechanism. The complex nanospheres were synthesized by introducing ferric ions into the reaction mixture used for polymerization of dopamine. It is verified that both the oxidative polymerization of dopamine and Fe(III)-PDA complexation contribute to the "polymerization" process, in which the ferric ions form coordination bonds with both oxygen and nitrogen, as indicated by X-ray absorption fine-structure spectroscopy. In the "polymerization" process, the morphology of the complex nanostructures is gradually transformed from sheetlike to spherical at the feed Fe(III)/dopamine molar ratio of 1/3. The final size of the complex spheres is much smaller than its neat PDA counterpart. At higher feed Fe(III)/dopamine molar ratios, the final morphology of the "polymerization" products is sheetlike. The results suggest that the formation of spherical morphology is likely to be driven by covalent polymerization-induced decrease of hydrophilic functional groups, which causes reself-assembly of the PDA oligomers to reduce surface area. We also demonstrate that this one-pot synthesis route for hybrid nanospheres enables the facile construction of carbonized PDA (C-PDA) nanospheres uniformly embedded with Fe3O4 nanoparticles of only 3-5 nm in size. The C-PDA/Fe3O4 nanospheres exhibit catalytic activity toward oxygen reduction reaction and deliver a stable discharge voltage for over 200 h when utilized as the cathode in a primary Zn-air battery and are also good recyclable catalyst supports. PMID- 27550632 TI - Floquet edge states in germanene nanoribbons. AB - We theoretically demonstrate versatile electronic properties of germanene monolayers under circularly, linearly, and elliptically polarized light. We show for the high frequency regime that the edge states can be controlled by tuning the amplitude of the light and by applying a static electric field. For circularly polarized light the band gap in one valley is reduced and in the other enhanced, enabling single valley edge states. For linearly polarized light spin split states are found for both valleys, being connected by time reversal symmetry. The effects of elliptically polarized light are similar to those of circularly polarized light. The transport properties of zigzag nanoribbons in the presence of disorder confirm a nontrivial nature of the edge states under circularly and elliptically polarized light. PMID- 27550633 TI - Fusion genes in solid tumors: the possibilities and the pitfalls. PMID- 27550635 TI - An efficient approach toward formation of polycyclic coumarin derivatives via carbocation-initiated [4+2] cycloaddition and atom-economical photo-irradiated cyclization. AB - Facile carbocation-initiated [4+2] cycloaddition of o-anisole-substituted propargyl silyl ethers and ynamides led to the formation of 4-vinylcoumarins. Subsequent intramolecular cyclization of 3-aryl-4-vinylcoumarins afforded polycyclic coumarin derivatives 11,12-dihydronaphtho[1,2-c]chromen-5-ones in excellent yields under mild photo-irradiated conditions established by fluorescence analysis-oriented screening. PMID- 27550634 TI - Evaluating Parents' Self-Efficacy for Diabetes Management in Pediatric Type 1 Diabetes. AB - Objective: To examine the factor structure and construct validity of the Maternal Self-Efficacy for Diabetes Management Scale (MSED) in 135 youth ( Mage = 13.50 +/- 1.83 years), with type 1 diabetes mellitus. Method: The study used exploratory factor analysis (EFA) to examine the factor structure and correlations to examine relationships among MSED factors and select parent and child diabetes-related health behaviors and outcomes. Results: EFA identified an 11-item three-factor solution (chi 2 (25, n = 133) = 40.22, p < .03, RMSEA = 0.07, CFI = 0.98, TLI = 0.97), with factors corresponding to parents' perceived ability to manage their child's diabetes (MSED-M), problem-solve issues surrounding glycemic control (MSED-P), and teach their child about diabetes care (MSED-T). Correlational analyses revealed significant associations between the MSED-M and MSED-T and parent-reported optimism and youth's diabetes-specific self efficacy. The MSED-T was also associated with glycated hemoglobin and self monitoring blood glucose. Conclusions: Results provide preliminary evidence for the reliability and validity of a three-factor solution of the MSED. PMID- 27550636 TI - Negative Outcomes of Poly(l-Lactic Acid) Fiber-Reinforced Scaffolds in an Ovine Total Meniscus Replacement Model. AB - Our objective was to test the efficacy of collagen-hyaluronan scaffolds reinforced with poly(l-lactic acid) (PLLA) fibers in an ovine total meniscus replacement model. Scaffolds were implanted into 9 sheep (n = 1 at 8 weeks, n = 2 at 16 weeks, n = 3 at both 24, 32 weeks) following total medial meniscectomy. From 16 weeks on, explants were characterized by confined compression creep, histological, and biochemical analyses. Articular surfaces were observed macroscopically and damage was ranked histologically using the Mankin score. At sacrifice, three of the nine PLLA scaffolds had completely ruptured, and the intact scaffolds experienced progressive shape changes and severe narrowing in the body region at 16, 24, and 32 weeks. Aggregate compressive modulus and permeability did not improve with time. Histological and biochemical analyses showed significantly less extracellular matrix and less matrix organization compared to native tissue. Osteophytes, bone erosion, and cartilage damage were observed, increasing with time postimplantation. A buildup of lactic acid and/or the rapid loss of scaffold mechanical integrity due to PLLA degradation are probable causes for the joint abnormalities observed in this study. These results are in sharp contrast to those of our previous successful total meniscus replacement studies using polyarylate [p(DTD DD)] fiber-reinforced scaffolds. This suggests that PLLA fiber as produced in this study cannot be used as reinforcement for a meniscus replacement scaffold. PMID- 27550638 TI - A block copolymer-templated construction approach for the creation of nano patterned polyelectrolyte multilayers and nanoscale objects. AB - A block copolymer-based assembly approach for the creation of nano-patterned polyelectrolyte multilayers over cm2-scale areas is presented. Up to 5 bi-layers were selectively assembled on top of specific nano-domains featuring different morphologies. The successful isolation of nanoscale objects corresponding in shape to the template features is also demonstrated. This methodology is applicable to different types of polyelectrolytes, and opens up a new dimension for layer-by-layer construction. PMID- 27550639 TI - Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase. AB - N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains. Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes. This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine N(epsilon)-acetyltransferase (KAT) activity to catalyze the acetylation of lysine epsilon-amine. Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA). The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the beta7-beta8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures. Remarkably, we found that the side-chain of Phe 34 can influence the position of the coenzyme, indicating a new regulatory mechanism involving enzyme, co-factor and substrates interactions. Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved beta3-beta4 long loop participates in the regulation of hNaa60 activity. PMID- 27550640 TI - Communicative functions of directional verbal probabilities: Speaker's choice, listener's inference, and reference points. AB - Verbal probabilities have directional communicative functions, and most can be categorized as positive (e.g., "it is likely") or negative (e.g., "it is doubtful"). We examined the communicative functions of verbal probabilities based on the reference point hypothesis According to this hypothesis, listeners are sensitive to and can infer a speaker's reference points based on the speaker's selected directionality. In four experiments (two of which examined speakers' choice of directionality and two of which examined listeners' inferences about a speaker's reference point), we found that listeners could make inferences about speakers' reference points based on the stated directionality of verbal probability. Thus, the directionality of verbal probabilities serves the communicative function of conveying information about a speaker's reference point. PMID- 27550642 TI - Molecular vibrational trapping revisited: a case study with D2. AB - The present theoretical study is concerned with the vibrational trapping or bond hardening, which is a well-known phenomenon predicted by a dressed state representation of small molecules like and in an intense laser field. This phenomenon is associated with a condition where the energy of the light induced, vibrational level coincides with one of the vibrational levels on the field-free potential curve, which at the same time maximizes the wave function overlap between these two levels. One-dimensional numerical simulations were performed to investigate this phenomenon in a more quantitative way than has been done previously by calculating the photodissociation probability of for a wide range of photon energy. The obtained results undoubtedly show that the nodal structure of the field-free vibrational wave functions plays a decisive role in the vibrational trapping, in addition to the current understanding of this phenomenon. PMID- 27550641 TI - A novel transcription factor-like gene SbSDR1 acts as a molecular switch and confers salt and osmotic endurance to transgenic tobacco. AB - A salt- and drought-responsive novel gene SbSDR1 is predominantly localised to the nucleus, up-regulated under abiotic stresses and is involved in the regulation of metabolic processes. SbSDR1 showed DNA-binding activity to genomic DNA, microarray analysis revealed the upregulation of host stress-responsive genes and the results suggest that SbSDR1 acts as a transcription factor. Overexpression of SbSDR1 did not affect the growth and yield of transgenic plants in non-stress conditions. Moreover, the overexpression of SbSDR1 stimulates the growth of plants and enhances their physiological status by modulating the physiology and inhibiting the accumulation of reactive oxygen species under salt and osmotic stress. Transgenic plants that overexpressed SbSDR1 had a higher relative water content, membrane integrity and concentration of proline and total soluble sugars, whereas they showed less electrolyte leakage and lipid peroxidation than wild type plants under stress conditions. In field conditions, SbSDR1 plants recovered from stress-induced injuries and could complete their life cycle. This study suggests that SbSDR1 functions as a molecular switch and contributes to salt and osmotic tolerance at different growth stages. Overall, SbSDR1 is a potential candidate to be used for engineering salt and drought tolerance in crops without adverse effects on growth and yield. PMID- 27550643 TI - Sociodemographic, psychosocial and physical health correlates of common mental disorder symptoms among mothers in Trinidad and Tobago: Examining ethnic variations. AB - Historical and cultural experiences have shaped the life experiences of cultural communities in Trinidad and Tobago. Using a cultural focus, the goal of this investigation was to examine ethnic variations both in the prevalence of common mental disorder (CMD) symptoms as well as in the associations between sociodemographic, psychosocial, physical health correlates and CMDs among mothers in Trinidad and Tobago. Participants included 1002 mothers (359 African-, 353 Indo- and 290 Mixed-Ethnic Trinidadian). Mean comparisons indicated similarities in the levels of depression, somatisation and anxiety across ethnic groups. The associations between physical ill health, experiences of pain and depression and between physical ill health and somatisation were stronger for Mixed-Ethnic Trinidadian than Indo-Trinidadian mothers. The relationship between early experiences of domestic violence and depression was stronger for Indo-Trinidadian than Mixed-Ethnic Trinidadian mothers. The associations between early experiences of domestic violence and depression and between experiences of pain and somatisation were stronger for African Trinidadian than Mixed-Ethnic Trinidadian mothers. Thus beyond the direct effects, mothers belonging to specific ethnic groups indicated greater or lesser vulnerabilities to CMDs depending on their exposure to specific correlates. Results have applicability for the development of culturally sensitive interventions for mothers experiencing CMDs. PMID- 27550644 TI - Respite needs of families receiving palliative care. AB - AIM: The care of a child with a life-limiting condition proves an emotional, physical and financial strain on the family that provides care for their child. Respite care is one way which allows carers to receive some relief and support in the context of this burden of care. The provision of and the requirements for respite in this context is poorly understood. This survey aims to describe the types of respite care families receive, the respite that they would ideally receive and the barriers that prevent this. METHODS: A cohort of 34 families cared for by the Paediatric Palliative Care Service in Queensland were approached to participate in a 20-question survey about their current respite preferences for future respite, with 20 surveys returned. RESULTS: Three of the families (15%) reported receiving no respite in the previous 12 months. Families who received respite received a combination of formal respite (a structured care provider) and informal respite (family or friends). Ten families (50%) reported that they would want the time of respite changed. Barriers to receiving adequate respite included complexity of care of the child, financial barriers and lack of a respite provider. CONCLUSIONS: There is disparate provision of respite care with the main perceived barrier to attaining 'ideal respite' being the lack of a provider able to meet the complex care needs of their child. The provision of respite across diversity in geography; medical condition; social and cultural needs remains a challenge. PMID- 27550645 TI - Risk of cancer in patients with polycystic kidney disease: a propensity-score matched analysis of a nationwide, population-based cohort study. AB - BACKGROUND: Data for the risk of any solid cancer in patients with polycystic kidney disease are scarce. Therefore, we did a nationwide cohort study in Taiwan to establish the risk of cancer in patients with polycystic kidney disease without either chronic kidney disease or end-stage renal disease. METHODS: From inpatient claims of the Taiwan National Health Insurance Research Database, we included patients aged 20 years and older and diagnosed with polycystic kidney disease between January, 1998 and December, 2010, in the polycystic kidney disease cohort. Patients with a history of cancer, a history of chronic kidney disease or of end-stage renal disease (recorded from the Registry of Catastrophic Illness Patient Database) were excluded. For each patient with polycystic kidney disease, one patient aged older than 20 years with no history of polycystic kidney disease or cancer was randomly selected from the National Health Insurance Research Database, matched 1:1 on the basis of the propensity score calculated by logistic regression, and was included in the control non-polycystic kidney disease cohort. The follow-up period for each patient was estimated from the index date to the date of diagnosis of cancer, or the patient was censored due to withdrawal from the insurance programme (eg, death, immigration, or imprisonment) or on Dec 31, 2011. The primary outcome of interest was a diagnosis of cancer during a 14-year follow-up period. The risk of cancer was represented as a hazard ratio (HR) calculated in Cox proportional hazard regression models. FINDINGS: 4346 patients with polycystic kidney disease and 4346 without were enrolled in the study. The median follow-up period in the polycystic kidney disease cohort was 3.72 years (IQR 1.25-7.31) and in the non-polycystic kidney disease cohort was 4.96 years (2.29-8.38). The overall incidence of cancer was higher in the polycystic kidney disease cohort than in the control cohort (20.1 [95% CI 18.3 21.9] per 1000 person-years vs 10.9 [10.1-11.8] per 1000 person-years; crude hazard ratio (HR) 1.77 [95% CI 1.52-2.07]; HR adjusted for age, sex, frequency of medical visits, and comorbidities was 1.83 [1.57-2.15]). The specific risks (adjusted subhazard ratios) were significantly higher in the polycystic kidney disease cohort than that in the non-polycystic kidney disease cohort for liver cancer (1.49 [95% CI 1.04-2.13]; p=0.030), colon cancer (1.63 [1.15-2.30]; p=0.006), and kidney cancer (2.45 [1.29-4.65]; p=0.006). INTERPRETATION: To our knowledge, this is the first report of the association of polycystic kidney disease without end-stage renal disease with the risk of liver, colon, and kidney cancer. Health-care professionals should be aware of this risk, when treating patients with polycystic kidney disease. FUNDING: Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence, Academia Sinica Taiwan Biobank, Stroke Biosignature Project, NRPB Stroke Clinical Trial Consortium, Tseng-Lien Lin Foundation, Taiwan Brain Disease Foundation, Katsuzo and Kiyo Aoshima Memorial Funds, China Medical University Hospital, and Taiwan Ministry of Education. PMID- 27550646 TI - Cancer overtakes heart disease as biggest killer in 12 countries. PMID- 27550647 TI - Cancer in patients with inherited ciliopathies: polycystic kidney disease. PMID- 27550648 TI - Masked Hypertension and Left Atrial Dysfunction: A Hidden Association. AB - Masked hypertension (MH) is a clinical condition that indicates normal values of clinic blood pressure (BP) but elevated 24-hour BP. The purpose of this study was to investigate the relationship between MH and left atrial (LA) phasic function evaluated by both the volumetric and speckle tracking method. This cross sectional study included 49 normotensive individuals, 50 patients with MH, and 70 untreated sustained hypertensive patients adjusted by age and sex. MH was diagnosed if clinic BP was normal and 24-hour BP was increased. LA reservoir function was lower in patients with MH and those with sustained hypertension compared with the normotensive group. LA conduit function gradually decreased, while LA booster pump function progressively increased, from normotension to sustained hypertension. Similar results were obtained by two-dimensional echocardiographic strain analysis. Independently of main clinic and echocardiographic characteristics, 24-hour systolic BP was associated with LA passive ejection fraction, LA total longitudinal strain, LA positive longitudinal strain, and LA stiffness index. In conclusion, MH is associated with impairment of LA phasic function and stiffness, and 24-hour systolic BP increment was closely related with LA remodeling. PMID- 27550649 TI - Transcriptome and proteome characterization of surface ectoderm cells differentiated from human iPSCs. AB - Surface ectoderm (SE) cells give rise to structures including the epidermis and ectodermal associated appendages such as hair, eye, and the mammary gland. In this study, we validate a protocol that utilizes BMP4 and the gamma-secretase inhibitor DAPT to induce SE differentiation from human induced pluripotent stem cells (hiPSCs). hiPSC-differentiated SE cells expressed markers suggesting their commitment to the SE lineage. Computational analyses using integrated quantitative transcriptomic and proteomic profiling reveal that TGFbeta superfamily signaling pathways are preferentially activated in SE cells compared with hiPSCs. SE differentiation can be enhanced by selectively blocking TGFbeta RI signaling. We also show that SE cells and neural ectoderm cells possess distinct gene expression patterns and signaling networks as indicated by functional Ingenuity Pathway Analysis. Our findings advance current understanding of early human SE cell development and pave the way for modeling of SE-derived tissue development, studying disease pathogenesis, and development of regenerative medicine approaches. PMID- 27550650 TI - Measurement of patient safety: a systematic review of the reliability and validity of adverse event detection with record review. AB - OBJECTIVES: Record review is the most used method to quantify patient safety. We systematically reviewed the reliability and validity of adverse event detection with record review. DESIGN: A systematic review of the literature. METHODS: We searched PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Library and from their inception through February 2015. We included all studies that aimed to describe the reliability and/or validity of record review. Two reviewers conducted data extraction. We pooled kappa values (kappa) and analysed the differences in subgroups according to number of reviewers, reviewer experience and training level, adjusted for the prevalence of adverse events. RESULTS: In 25 studies, the psychometric data of the Global Trigger Tool (GTT) and the Harvard Medical Practice Study (HMPS) were reported and 24 studies were included for statistical pooling. The inter-rater reliability of the GTT and HMPS showed a pooled kappa of 0.65 and 0.55, respectively. The inter-rater agreement was statistically significantly higher when the group of reviewers within a study consisted of a maximum five reviewers. We found no studies reporting on the validity of the GTT and HMPS. CONCLUSIONS: The reliability of record review is moderate to substantial and improved when a small group of reviewers carried out record review. The validity of the record review method has never been evaluated, while clinical data registries, autopsy or direct observations of patient care are potential reference methods that can be used to test concurrent validity. PMID- 27550651 TI - Regional trends in avoidable hospitalisations due to complications among population with diabetes in Finland in 1996-2011: a register-based cohort study. AB - OBJECTIVES: Diabetes requires continuous medical care including prevention of acute complications and risk reduction for long-term complications. Diabetic complications impose a substantial burden on public health and care delivery. We examined trends in regional differences in hospitalisations due to diabetes related complications among the total diabetes population in Finland. RESEARCH DESIGN: A longitudinal register-based cohort study 1996-2011 among a total population with diabetes in Finland. PARTICIPANTS: All persons with diabetes identified from several administrative registers in Finland in 1964-2011 and alive on 1 January 1996. OUTCOME MEASURES: We examined hospitalisations due to diabetes-related short-term and long-term complications, uncomplicated diabetes, myocardial infarction, stroke, lower extremity amputation and end-stage renal disease (ESRD). We calculated annual age-adjusted rates per 10 000 person years and the systematic component of variation. Multilevel models were used for studying time trends in regional variation. RESULTS: There was a steep decline in complication-related hospitalisation rates during the study period. The decline was relatively small in ESRD (30%), whereas rates of hospitalisations for short term and long-term complications as well as uncomplicated diabetes diminished by about 80%. The overall correlation between hospital district intercepts and slopes in time was -0.72 (p<0.001) among men and -0.99 (p<0.001) among women indicating diminishing variation. Diminishing variation was found in each of the complications studied. The variation was mainly distributed at the health centre level. CONCLUSIONS: Our study suggests that the prevention of complications among persons with diabetes has improved in Finland between 1996 and 2011. The results further suggest that the prevention of complications has become more uniform throughout the country. PMID- 27550653 TI - Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects. AB - PURPOSE: Several severe drug interactions have been reported when sildenafil, a potent drug for the treatment of erectile dysfunction, is co-administered with drugs or herbal remedies that inhibit cytochrome P450 (CYP) 3A4. This study evaluates the effects of two citrus fruit juices, lemon and Seville orange, on the pharmacokinetics of sildenafil in male healthy subjects following a single oral dose. METHODS: We conducted an open-label, three-way crossover study in nine healthy male volunteers. Participants received a single oral dose of sildenafil (50 mg) after pretreatment with 250 mL of either water (control), undiluted lemon juice, or Seville orange juice for 3 consecutive days. All subjects were monitored for adverse effects during the study period. Plasma samples were collected for 12 h after dosing and analyzed for sildenafil concentration. RESULTS: Compared with pretreatment with water, Seville orange juice significantly increased the area under the plasma concentration-time curve from time zero to infinity and the peak plasma concentration of sildenafil by 44 % (90 % confidence interval [CI] 30-60) and 18 % (90 % CI 108-129), respectively, without affecting the time to reach peak plasma concentration. Additionally, Seville orange juice significantly reduced the apparent oral clearance of sildenafil by 30 % (90 % CI 63-75) without affecting its elimination half-life. In contrast, lemon juice did not cause any significant alterations in the pharmacokinetics of sildenafil. There was no significant treatment-related adverse effects reported during the study. CONCLUSIONS: Although it is considered as a moderate CYP3A4 inhibitor, Seville orange only caused a mild increase in exposure to sildenafil after a single oral dose, without manifestation of any adverse effects. The enhanced bioavailability of sildenafil by Seville orange may be attributed to inhibition of its intestinal first-pass effect (CYP3A4 and or p glycoprotein). Lemon juice, in contrast, had no effects on the pharmacokinetics of sildenafil. PMID- 27550652 TI - Understanding the role of sleep in suicide risk: qualitative interview study. AB - OBJECTIVE: Sleep problems are associated with increased risk of suicide, independent of depression. This analysis explores narrative accounts of the role of sleep in relation to suicidal thoughts and behaviours. DESIGN: Qualitative study, based on in-depth semistructured interviews which were analysed with an inductive, latent thematic analysis. PARTICIPANTS: A maximum variation sample of 18 people with experience of a major depressive episode, and suicidal thoughts and behaviours. SETTING: Primary care, North West England. RESULTS: Respondents emphasised the importance of sleep for recovery and management of their mental well-being. Moreover, three inter-related pathways were identified, whereby beliefs about sleep contributed to suicidal thoughts and behaviours. First, being awake during the biological night heightened risk of suicidal behaviours, as this was perceived to be an opportune time for a suicide attempt due to the decreased chances that a friend of family member would intervene during a suicide attempt. Additionally, the reduction in available support at night added to suicide risk. Second, failure to achieve good sleep was perceived to make life harder through contributing to core features of depression, such as negative thinking, attention difficulties and inactivity. Third, sleep acted as an alternative to suicide, by providing an escape from problems, including mental health problems, in waking life. However, this desire to sleep to escape was associated with excessive daytime sleeping, which subsequently may reinforce disturbed sleeping patterns. CONCLUSIONS: Sleep problems should be an important treatment target when working with suicidal clients. More broadly, night-time service provision should be considered when developing suicide prevention initiatives. PMID- 27550654 TI - Characterization of the Biodistribution and Systemic Absorption of TT-173, a New Hemostatic Agent of Recombinant Human Tissue Factor, Using Radiolabeling with 18F. AB - BACKGROUND AND OBJECTIVES: TT-173 is the first topical hemostatic agent based on tissue factor. To prevent thromboembolic events and intravascular coagulation it is necessary to rule out the systemic absorption of new bioactive hemostats. Here, we radiolabeled TT-173 with [18F]SBF to characterize its systemic absorption and biodistribution. METHODS: A group of rats were administered intravenously with [18F]TT-173 and were subjected to a positron emission tomography study. A second group of animals received the [18F]TT-173 topically over a skin lesion in the flank. Topical absorption was quantified and the biodistribution patterns observed were compared. RESULTS: After topical application, low amounts of [18F]TT-173 were absorbed and distributed without relevant accumulation in any organ. On the other hand, after intravenous injection, [18F]TT-173 accumulated in lungs, liver and spleen, consistent with intravascular clot formation and the posterior capillary trapping and phagocytosis by the reticuloendothelial system. In both cases, a substantial concentration of radioactive product was found in urine consistent with renal excretion of degradation products of [18F]TT-173. CONCLUSIONS: After topical application, [18F]TT-173 did not show a significant systemic accumulation in animal organs. Minor radioactive concentration found in lungs, liver and spleen likely corresponds with fragments of the product without procoagulant activity. Radiolabeling with [18F]SFB enables the characterization of systemic absorption and biodistribution of new topical hemostats like TT-173. PMID- 27550655 TI - Multiple Dose Pharmacokinetics and Safety of Sulcardine Sulfate in Healthy Chinese Male Subjects: An Open-Label Phase I Clinical Study. AB - BACKGROUND: Sulcardine sulfate is a novel antiarrhythmic agent with mechanism of action as a multi-ion channel blocker. Preclinical studies in animal models have demonstrated that sulcardine sulfate is efficacious in atrial and ventricular arrhythmias, and consequently, leads to the prevention of sudden cardiac death. OBJECTIVES: This study was conducted in healthy Chinese male subjects to investigate the pharmacokinetic profile and safety of sulcardine sulfate after repeated oral dose administration at 200, 400, and 800 mg for 5 days. METHODS: Thirty-three male subjects were enrolled in this study. In the multiple dose phase, sulcardine sulfate was administered orally twice at the interval of q12 h since day 3. Sulcardine sulfate plasma concentration was determined using a validated LC-MS/MS method. Safety was assessed using clinical evaluation and AE monitoring. RESULTS: In this repeated dose study, pharmacokinetic parameters (C max, AUC(0-t), and C ss_av) increased with the increase in dose (the dose ratio of the three cohorts was 1:2:4, while the ratio of C max and AUC(0-t) at day 1 was around 1:4:9 and 1:4:6, respectively), but in a non-linear fashion. The accumulation ratio at steady state (AR) of 200, 400, and 800 mg dose level was 1.18, 1.69, and 2.13, respectively, indicating that sulcardine sulfate has a modest accumulation upon repeated dose administration. Monitoring of pre-dose plasma concentrations on days 6, 7, and 8 for each dose level indicated that steady state was achieved at day 6 after three-day repeated dosing. CONCLUSIONS: Pharmacokinetic characteristics of sulcardine sulfate were shown to be non linear, with the modest accumulation upon repeated dosing, and sulcardine sulfate was safe and well tolerated. PMID- 27550656 TI - Learning Specificity and Segmentation Strategies: Misconceptions Regarding Computerized-Cognitive Training Programs. PMID- 27550657 TI - [The Scaphoid bone]. PMID- 27550658 TI - Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4. AB - The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr(-/-) mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr(-/-) mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr(-/-) mice. Mechanistically, the heightened inflammation in Pxr(-/-) mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection. PMID- 27550659 TI - Left atrial volumetric assessment using a novel automated framework for 3D echocardiography: a multi-centre analysis. AB - Aims: This study aims at validating a software tool for automated segmentation and quantification of the left atrium (LA) from 3D echocardiography. Methods and results: The LA segmentation tool uses a dual-chamber model of the left side of the heart to automatically detect and track the atrio-ventricular plane and the LA endocardium in transthoracic 3D echocardiography. The tool was tested in a dataset of 121 ultrasound images from patients with several cardiovascular pathologies (in a multi-centre setting), and the resulting volumes were compared with those assessed manually by experts in a blinded analysis using conventional contouring. Bland-Altman analysis showed good agreement between the automated method and the manual references, with differences (mean +/- 1.96 SD) of 0.5 +/- 5.7 mL for LA minimum volume and -1.6 +/- 9.7 mL for LA maximum volume (comparable to the inter-observer variability of manual tracings). The automated tool required no user interaction in 93% of the recordings, while 4% required a single click and only 2% required contour adjustments, reducing considerably the amount of time and effort required for LA volumetric analysis. Conclusion: The automated tool was validated in a multi-centre setting, providing quantification of the LA volume over the cardiac cycle with minimal user interaction. The results of the automated analysis were in agreement with those estimated manually by experts. This study shows that such approach has clinical utility for the assessment of the LA morphology and function, automating and facilitating the time-consuming task of analysing 3D echocardiographic recordings. PMID- 27550660 TI - Prevalence of unrecognized myocardial infarction in a low-intermediate risk asymptomatic cohort and its relation to systemic atherosclerosis. AB - Aims: Unrecognized myocardial infarctions (UMIs) have been described in 19-30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI). Methods and results: A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of <20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid myocardium (n = 4), epicardium (n = 1), or right ventricular insertion points (n = 2). Those with UMI had a significantly higher BNP [median 116 (range 31-133) vs. 22.6 (5-175) pg/mL, P = 0.015], lower ejection fraction [54.6 (36-62) vs. 68.9 (38-89)%, P = 0.007], and larger end-systolic volume [36.3 (27-61) vs. 21.7 (5-65) mL/m2, P = 0.014]. Those with non-specific LGE had lower diastolic blood pressure [68 (54-70) vs. 72 (46-98) mmHg, P = 0.013] but no differences in their cardiac function. Conclusion: Despite previous reports describing high prevalence of UMI in older populations, in a predominantly middle-aged cohort, those who are of intermediate or low cardiovascular risk have a very low risk of having an unrecognized myocardial infarct. PMID- 27550661 TI - Liver fat is related to cardiovascular risk factors and subclinical vascular disease: the Rotterdam Study. AB - AIMS: Increasing evidence suggests involvement of the amount of liver fat in the development of cardiovascular disease. We investigated the relation of liver fat with cardiovascular risk factors and subclinical vascular disease in the general population. METHODS AND RESULTS: Between 2003 and 2006, 2351 persons from the population-based Rotterdam Study (mean age 69.6 +/- 6.7 years, 47.2% males) underwent non-enhanced computed tomography. We measured the mean liver attenuation value in Hounsfield units and quantified the following markers of subclinical vascular disease: epicardial fat volume and volumes of coronary (CAC), aortic (AAC), extracranial (ECAC), and intracranial carotid calcification (ICAC). Using linear regression, we investigated associations between traditional cardiovascular risk factors and mean liver attenuation. We also investigated relations of mean liver attenuation with markers of subclinical vascular disease, adjusting for cardiovascular risk factors. We found strong associations of waist circumference, diastolic blood pressure, and diabetes with lower mean liver attenuation [multivariable-adjusted beta per unit increase in waist circumference: -2.54 (95% CI: -3.10; -1.99); diastolic blood pressure: -0.52 (95% CI: -0.88; -0.17); and the presence of diabetes: -21.91 (95% CI: -31.76; 12.06)]. Moreover, we found that larger mean liver attenuation values were associated with smaller volumes of epicardial fat and CAC, independent of cardiovascular risk factors [beta per 1-SD increase in mean liver attenuation value: -0.05 (95% CI: -0.08; -0.02) and -0.05 (95% CI: -0.10; -0.01), respectively]. CONCLUSION: Larger amounts of liver fat are related to larger volumes of epicardial fat and CAC, independent of traditional cardiovascular risk factors, providing important novel insights into the role of liver fat as a marker of vascular disease. PMID- 27550662 TI - The power of ultrasound: treating secondary MR with sound waves. PMID- 27550663 TI - Interatrial dissociation in an unoperated patient confirmed by echocardiography. PMID- 27550665 TI - Multimodality imaging of a congenital diverticulum of the left ventricular outflow tract. PMID- 27550666 TI - Facing the research challenge. PMID- 27550664 TI - Comments on potential health effects of MRI-induced DNA lesions: quality is more important to consider than quantity. AB - Magnetic resonance imaging (MRI) is increasingly being used in cardiology to detect heart disease and guide therapy. It is mooted to be a safer alternative to imaging techniques, such as computed tomography (CT) or coronary angiographic imaging. However, there has recently been an increased interest in the potential long-term health risks of MRI, especially in the light of the controversy resulting from a small number of research studies reporting an increase in DNA damage following exposure, with calls to limit its use and avoid unnecessary examination, according to the precautionary principle. Overall the published data are somewhat limited and inconsistent; the ability of MRI to produce DNA lesions has yet to be robustly demonstrated and future experiments should be carefully designed to optimize sensitivity and benchmarked to validate and assess reproducibility. The majority of the current studies have focussed on the initial induction of DNA damage, and this has led to comparisons between the reported induction of gammaH2AX and implied double-strand break (DSB) yields produced following MRI with induction by imaging techniques using ionizing radiation. However, gammaH2AX is not only a marker of classical double-ended DSB, but also a marker of stalled replication forks and in certain circumstances stalled DNA transcription. Additionally, ionizing radiation is efficient at producing complex DNA damage, unique to ionizing radiation, with an associated reduction in repairability. Even if the fields associated with MRI are capable of producing DNA damage, the lesions produced will in general be simple, similar to those produced by endogenous processes. It is therefore inappropriate to try and infer cancer risk by simply comparing the yields of gammaH2AX foci or DNA lesions potentially produced by MRI to those produced by a given exposure of ionizing radiation, which will generally be more biologically effective and have a greater probability of leading to long-term health effects. As a result, it is important to concentrate on more relevant downstream end points (e.g. chromosome aberration production), along with potential mechanisms by which MRI may lead to DNA lesions. This could potentially involve a perturbation in homeostasis of oxidative stress, modifying the background rate of endogenous DNA damage induction. In summary, what the field needs at the moment is more research and less fear mongering. PMID- 27550703 TI - Selection of Temporal Lags When Modeling Economic and Financial Processes. AB - This paper suggests new nonparametric statistical tools and procedures for modeling linear and nonlinear univariate economic and financial processes. In particular, the tools presented help in selecting relevant lags in the model description of a general linear or nonlinear time series; that is, nonlinear models are not a restriction. The tests seem to be robust to the selection of free parameters. We also show that the test can be used as a diagnostic tool for well-defined models. PMID- 27550704 TI - Model Comparison for Abiotic versus Biotic Pollen Dispersal. AB - An agent-based model with a correlated random walk is used to explore pollination within a forest. For abiotic dispersal, say via the wind, we use a purely random walk where there is no correlation between consecutive steps and for biotic dispersal, say via insect, we use a moderate or highly correlated random walk. In particular, we examine the differences in a number of biological measurement between a purely random walk and a correlated random walk in terms of gene dispersal in low and high plant densities. PMID- 27550705 TI - Mother-Infant Verbal and Nonverbal Interaction as Predictor of Attachment: Nonlinear Dynamic Analyses. AB - This longitudinal study examined flexibility in early mother-infant interaction at the age of approximately 6 months (N=30) and whether flexibility indices predicted (in) secure child attachment at 15 months. Dyadic flexibility was measured using dynamic systems-based modelling of patterns during mother-child free play in terms of NDS variables derived from SSG: the propensity to change states (dynamic flexibility), number of states visited (diversity) and predictability (dispersion). Results showed significant discriminant functions on the attachment type groups, A, B & C, for the total grid, which included verbal and non-verbal, and for the reciprocal verbal region. Specifically, the prediction outcomes seem to work better in total grid for A-dyads and in the reciprocal verbal region for B and C-dyads. Diversity emerged as the most relevant index in dyadic flexibility: A-dyads showed the least diversity, distinguished them from B-dyads in the verbal regions, (both the reciprocal and non-reciprocal, 'child verbal-mother non-verbal' one), and, from C-dyads in the reciprocal non-verbal region. A-dyads showed remarkably low activity in the regions involving child verbal behavior, showing that children who became avoidant attached at 15 months of age, were mostly silent at approximately 6 months, when they interacted with their mothers. Findings in this study contribute to advancing conceptually informed measurement of dyadic interaction to provide a new perspective on maternal sensitivity and early markers of child insecure/secure attachment. PMID- 27550706 TI - Cognitive Workload and Fatigue in a Vigilance Dual Task: Miss Errors, False Alarms, and the Effect of Wearing Biometric Sensors While Working. AB - The effects of workload, fatigue, and practice on the performance of cognitive tasks are often intertwined. Previous research has shown that these influences can be separated with the two cusp catastrophe models. This study expanded an earlier investigation of the two models for workload and fatigue in a vigilance task to include a wider range of bifurcation variables that could affect the elasticity versus rigidity of the operator in response to workload and added performance variability resulting from fatigue. The study also responded to a concern in the literature that performance on cognitive tasks can be complicated by adaptive responses to artificial task situations and thus distort underlying cognitive events. Therefore, we also explored whether wearing biometric sensors, frequently used in workload studies, can affect performance dynamics. Participants were 279 undergraduates who responded to target stimuli that appeared on a simulated security camera display at three rates of speed while completing a secondary task. Participants worked alone, in pairs, or in pairs wearing GSR sensors. Results supported the efficacy of the two models and isolated the impact of wearing sensors on the fatigue process. The strongest control variables across both the workload and fatigue models were field independence, anxiety, indecisiveness, inflexibility, secondary task completion, working in pairs, and wearing the sensors. The contributing effect of wearing sensors could possibly extend to other types of wearable technologies. PMID- 27550707 TI - A Cusp Catastrophe Model for Team Learning, Team Potency and Team Culture. AB - This paper examines team learning behaviors within a nonlinear dynamical system (NDS) perspective. The present research is based on a sample of 36 project workgroups, where data were collected at two moments of their life cycle, with visual analogue scales. Using both the least squares method and maximum likelihood, it proposes a cusp catastrophe model for explaining team learning. The cusp model is superior to its linear alternatives and implements team culture as the asymmetry variable and team potency as bifurcation. The findings of cusp structure in the data support the existence of discontinuous shifts in learning behavior and furthermore a proposition that the punctuated equilibrium model (PEM) might be a reasonable model for describing group functioning, since it encompasses such sudden changes between distinct stages (attractors). A discussion on small group research is also provided by highlighting the nonlinear dynamics of team processes, along with further implications for research and practice. PMID- 27550708 TI - Computational Insight to Improve the Thermal Isomerisation Performance of Overcrowded Alkene-Based Molecular Motors through Structural Redesign. AB - Synthetic overcrowded alkene-based molecular motors achieve 360 degrees unidirectional rotary motion of one motor half (rotator) relative to the other (stator) through sequential photochemical and thermal isomerisation steps. In order to facilitate and expand the use of these motors for various applications, it is important to investigate ways to increase the rates and efficiencies of the reactions governing the rotary motion. Here, we use computational methods to explore whether the thermal isomerisation performance of some of the fastest available motors of this type can be further improved by reducing the sizes of the motor halves. Presenting three new redesigned motors that combine an indanylidene rotator with a cyclohexadiene, pyran or thiopyran stator, we first use multiconfigurational quantum chemical methods to verify that the photoisomerisations of these motors sustain unidirectional rotary motion. Then, by performing density functional calculations, we identify both stepwise and concerted mechanisms for the thermal isomerisations of the motors and show that the rate-determining free-energy barriers of these processes are up to 25 kJ mol 1 smaller than those of the original motors. Furthermore, the thermal isomerisations of the redesigned motors proceed in fewer steps. Altogether, the results suggest that the redesigned motors are useful templates for improving the thermal isomerisation performance of existing overcrowded alkene-based motors. PMID- 27550709 TI - Synergetic recognition and separation of kelthane and pyridaben base on magnetic molecularly imprinted polymer nanospheres. AB - We present novel magnetic composite nanospheres for the preparation of a nanoiron oxide/carbon dots/beta-cyclodextrin/molecularly imprinted polymer for the selective solid-phase extraction kelthane and pyridaben from vegetables. The molecularly imprinted polymer was synthesized on the surface of nano-iron oxide/carbon dots via a chemical polymerization procedure, where kelthane-beta cyclodextrin and pyridaben-beta-cyclodextrin inclusion complexes were used as template molecules, and their adsorption behavior was investigated in detail. Characterization analysis and binding experiments revealed that magnetic composite nanospheres had outstanding magnetic properties, a large adsorption capacity, and high competitive selectivity for kelthane and pyridaben. The magnetic composite nanospheres were employed as an adsorbent in solid-phase extraction for the determination of kelthane and pyridaben in vegetable samples. The recoveries of kelthane and pyridaben were 92.8-105.2 and 94.4-104.6%, respectively. PMID- 27550710 TI - Type D personality, illness perception, social support and quality of life in continuous ambulatory peritoneal dialysis patients. AB - The previous studies reported Type D was associated with poor quality of life (QoL), increased psychological distress, and impaired health status in cardiac patients. The aim of this study is to assess the relationships among Type D personality, illness perception, social support, and investigate the impact of Type D personality on QoL in continuous ambulatory peritoneal dialysis (CAPD) patients. Type D personality was assessed by the Chinese 14-item Type D Personality Scale (DS14). Illness perceptions were assessed using the Chinese version of the Brief Illness Perception Questionnaire (B-IPQ). Social support status was assessed by the well-validated social support rating scale (SSRS). Patients' QoL was assessed by using Medical Outcomes Short Form 36 (SF-36), respectively. The Type Ds had significantly lower objective support score (8.18 +/- 2.56 vs. 9.67 +/- 3.28, p = 0.0001), subjective support score (6.71 +/- 2.0 vs. 7.62 +/- 1.93, p = 0.0001) and utilization of social support score (6.76 +/- 2.0 vs. 7.61 +/- 1.94, p = 0.0001) than that of the non-type Ds. Type Ds believed their illness had much more serious consequences (7.67 +/- 2.64 vs. 6.27 +/- 3.45, p < 0.001), and experience much more symptoms that they attributed to their illness (6.65 +/- 2.54 vs. 7.31 +/- 2.36, p = 0.023). Significant differences were found between Type Ds and non-Type Ds in PCS (40.53 +/- 6.42 vs. 48.54 +/- 6.21 p < 0.001) and MCS (41.7 1 +/- 10.20 vs. 46.35 +/- 9.31, p = 0.012). The correlation analysis demonstrated that Type D was negatively associated with physical component score (PCS) (r = -0.29, p < 0.01), mental component score (MCS) (r = -0.31, p < 0.01), and social support (r = -0.24, p < 0.001). Using multiple linear regression analysis, we found that Type D personality was independently associated with PCS (beta = -0.32, p < 0.001) and MCS (beta = 0.24, p < 0.001). Type D personality was a predictor of poor QoL in CAPD patients. The current study is the first to identify a strong association among Type D, illness perceptions, social support and QoL in CAPD patients. The worse illness perceptions and lower social support level therefore represent possible mechanisms to explain the link between Type D and poor QoL in CAPD patients. PMID- 27550711 TI - Minocycline in leprosy patients with recent onset clinical nerve function impairment. AB - Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy. PMID- 27550712 TI - Synchrony and Defibrillation: What Is the Mechanism? PMID- 27550714 TI - Multiple cutaneous metastases as the first sign of mantle cell lymphoma associated with multiple HPV 52-positive squamous cell carcinomas of the skin. PMID- 27550713 TI - Myeloperoxidase Inhibition Increases Neurogenesis after Ischemic Stroke. AB - The relationship between inflammation and neurogenesis in stroke is currently not well understood. Focal ischemia enhances cell proliferation and neurogenesis in the neurogenic regions, including the subventricular zone (SVZ), dentate gyrus, as well as the non-neurogenic striatum, and cortex in the ischemic hemisphere. Myeloperoxidase (MPO) is a potent oxidizing enzyme secreted during inflammation by activated leukocytes, and its enzymatic activity is highly elevated after stroke. In this study, we investigated whether the inhibition of MPO activity by a specific irreversible inhibitor, 4-aminobenzoic acid hydrazide (ABAH) (MPO-/- mice) can increase neurogenesis after transient middle cerebral artery occlusion in mice. ABAH administration increased the number of proliferating bromodeoxyuridine (BrdU)-positive cells expressing markers for neural stems cells, astrocytes, neuroprogenitor cells (Nestin), and neuroblasts (doublecortin) in the ischemic SVZ, anterior SVZ, striatum, and cortex. MPO inhibition also increased levels of brain-derived neurotrophic factor, phosphorylation of cAMP response element-binding protein (Ser133), acetylated H3, and NeuN to promote neurogenesis in the ischemic SVZ. ABAH treatment also increased chemokine CXC receptor 4 expression in the ischemic SVZ. MPO-deficient mice treated with vehicle or ABAH both showed similar effects on the number of BrdU+ cells in the ischemic hemisphere, demonstrating that ABAH is specific to MPO. Taken together, our results underscore a detrimental role of MPO activity to postischemia neurogenesis and that a strategy to inhibit MPO activity can increase cell proliferation and improve neurogenesis after ischemic stroke. PMID- 27550715 TI - Evaluation of fetal cardiac valve anomalies by four-dimensional echocardiography with spatiotemporal image correlation (4DSTIC). AB - BACKGROUND: Prenatal diagnosis of cardiac valve anomalies challenged most screening sonographers. The purpose of the study was to evaluate the use of four dimensional echocardiography with spatiotemporal image correlation (4DSTIC) in detecting normal and abnormal fetal cardiac valves. METHODS: Forty-three cases of confirmed cardiac valve anomalies identified by two-dimensional echocardiography (2DE) were retrospectively reviewed in this study. Additional 121 confirmed normal fetuses were included as controls. Four-dimensional volumes were acquired from each fetus using a transverse sweep. Four-dimensional rendered images were retrieved from the volumes for each of the cardiac valves for the normal fetuses and for the intended valves for fetuses with valve malformations. RESULTS: The visualization rates of cardiac valves retrieved from 4D volumes in the normal fetuses ranged from 72.5% to 97.5% before 33 gestational weeks and from 46.3% to 80.5% in late pregnancy. Furthermore, 4D rendered images were successfully obtained in 38 of 43 (88.4%) fetuses with cardiac valve lesions. CONCLUSIONS: The 4D images and cine loops displayed the valves anatomy vividly in both normal and abnormal fetuses, including some subtle malformations which were not identified by traditional 2DE. The standardized protocol we propose herein was important in obtaining the 4D images from the volumes. The 4D modality allows a better visualization of fetal cardiac valves and should be considered a valuable addition to traditional 2DE imaging. PMID- 27550716 TI - An introduction to physiologically-based pharmacokinetic models. AB - Physiologically-based pharmacokinetic (PBPK) models represent drug kinetics in one or more 'real' organs (and hence require submodels of organs/tissues) and they describe 'whole-body' kinetics by joining together submodels with drug transport by blood flow as dictated by anatomy. They attempt to reproduce 'measureable' physiological and/or pharmacokinetic processes rather than more abstract rate constants and volumes. PBPK models may be built using a 'bottom-up' approach, where parameters are chosen from first principles, literature, or in vitro data as opposed to a 'top-down' approach, where all parameters are estimated from data. The basic principles of PBPK models are described, focusing on the equations for three individual organs: a single flow-limited compartment describing distribution only, a membrane-limited compartment describing distribution, and a single flow-limited compartment with elimination. These organ models are linked to make a basic three-compartment physiological model of the whole body. PBPK models are particularly suited to scaling kinetics across body size (e.g., adult to neonate) and species (e.g., animal to first-in-man) as physiology and pharmacology can be represented by independent parameters. Maturation models can be incorporated as for compartmental models. PBPK models are now available in commercial software packages, and are perhaps now more accessible than ever. Alternatively, even complex PBPK models can be represented in generic differential equation-solving software using the simple principles described here. The relative ease of constructing the code for PBPK models belies the most difficult aspect of their implementation-collecting, collating, and justifying the data used to parameterize the model. PMID- 27550717 TI - Effect of a dietary supplementation with linseed oil and selenium to growing rabbits on their productive performances, carcass traits and fresh and cooked meat quality. AB - The present experiment tested a dietary supplementation with linseed oil and selenium to growing rabbits. The basal diet (B) contained 3% sunflower oil, while it was substituted with 3% linseed oil in the experimental feed (S). The selenium (Se) content of the two diets was 0.10 vs. 0.46 mg/kg. Rabbits were fed with B diet from the age of 18 days. One group was fed with the B diet until 11 weeks of age (group B), whereas the experimental groups were fed with S diet for 1, 2, 3 or 4 weeks (groups S1, S2, S3 and S4, respectively), before slaughtering (11 weeks of age). Live performance and carcass traits of rabbits, fatty acid (FA) profile and selenium content of their hind leg (HL) and Longissimus thoracis et lumborum (LTL) meat were considered in this study. In addition, the effect of two different cooking methods on the nutritional value of the enriched HL meat was also assessed. The tested dietary supplementation only minimally affected the live performance and carcass traits of rabbits. The S supplementation significantly reduced the Sigma n-6 FA and increased the Sigma n-3 FA of the HL meat and LTL meat, compared to the B diet (p < 0.001); thus, n-6/n-3 ratio was improved (p < 0.001). In addition, HL meat and LTL meat of S fed rabbits were significantly enriched in Se reaching a twofold increase in both meat cuts (p < 0.01). Therefore, the S supplementation improved the functional value of the rabbit meat. The heat treatment affected cooking loss, Se and vitamin E contents as well as the oxidative status of the HL meat (p < 0.001), with the different cooking methods providing different results. In addition, even if the beneficial C20:5 n-3 and C22:6 n-3 decreased with cooking, the n-6/n-3 ratio remained unaffected. PMID- 27550718 TI - Oxaliplatin added to fluoropyrimidine for adjuvant treatment of colorectal cancer is associated with long-term impairment of peripheral nerve sensory function and quality of life. AB - BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) of acute and chronic type is well known, but long-term chronic type OIPN and its impact on quality of life (QoL) has not been extensively studied. Clinical experience indicates that oxaliplatin tolerance might vary with climate. MATERIAL AND METHODS: Patient reported chronic type OIPN and QoL among patients treated with oxaliplatin added to a fluoropyrimidine (Folfox or Capox) in the adjuvant setting of colorectal cancer (CRC) were assessed in a single center cross-sectional study by using the EORTC QLQ-CIPN20 and QLQ-C30 questionnaires. Comparison was made to patients treated with a fluoropyrimidine (5-FU or capecitabine) alone during the same time period. RESULTS: Of 161 patients being disease-free 1-8 years after stop of treatment and invited, 84% participated; 65 treated with oxaliplatin and 71 with a fluoropyrimidine alone. Mean cumulative oxaliplatin dose was 567 mg/m2 (55% of planned dose). Oxaliplatin-treated patients reported statistically and clinically significant worse sensory as well as motor scale scores, dominated by symptoms from the feet. Severe tingling and numbness in toes/feet was reported by 38% and 37%, respectively, by oxaliplatin-treated patients compared with 8% for both by fluoropyrimidine alone patients (p < 0.001). Subgroup analyses indicated no impact of gender, age, regimen, time since stop of treatment or cumulated oxaliplatin dose for severity of the chronic type OIPN. The oxaliplatin compared with the fluoropyrimidine group reported worse QoL scores throughout all domains, with statistically and clinically significant differences for role and social function, nausea/loss of appetite and financial problems. CONCLUSIONS: Oxaliplatin added to a fluoropyrimidine for adjuvant treatment of CRC in a country with subarctic climate is associated with long-term, seemingly chronic, sensory neuropathy and impairment of QoL. This should be taken into account in clinical decision making on oxaliplatin treatment in the adjuvant setting. PMID- 27550719 TI - Time-restricted feeding in young men performing resistance training: A randomized controlled trial. AB - A randomized controlled trial was conducted to examine eight weeks of resistance training (RT) with and without time-restricted feeding (TRF) in order to assess nutrient intake and changes in body composition and muscular strength in young recreationally active males. The TRF programme consisted of consuming all calories within a four-hour period of time for four days per week, but included no limitations on quantities or types of foods consumed. The RT programme was performed three days per week and consisted of alternating upper and lower body workouts. For each exercise, four sets leading to muscular failure between 8 and 12 repetitions were employed. Research visits were conducted at baseline, four, and eight weeks after study commencement. Measurements of total body composition by dual-energy X-ray absorptiometry and muscle cross-sectional area by ultrasound were obtained. Upper and lower body strength and endurance were assessed, and four-day dietary records were collected. TRF reduced energy intake by ~650 kcal per day of TRF, but did not affect total body composition within the duration of the study. Cross-sectional area of the biceps brachii and rectus femoris increased in both groups. Effect size data indicate a gain in lean soft tissue in the group that performed RT without TRF (+2.3 kg, d = 0.25). Upper and lower body strength and lower body muscular endurance increased in both groups, but effect sizes demonstrate greater improvements in the TRF group. Overall, TRF reduced energy intake and did not adversely affect lean mass retention or muscular improvements with short-term RT in young males. PMID- 27550720 TI - Photoionization-induced pi<-> H site switching dynamics in phenol(+)-Rg (Rg = Ar, Kr) dimers probed by picosecond time-resolved infrared spectroscopy. AB - The ionization-induced pi<-> H site switching reaction in phenol(+)-Rg (PhOH(+) Rg) dimers with Rg = Ar and Kr is traced in real time by picosecond time-resolved infrared (ps-TRIR) spectroscopy. The ps-TRIR spectra show the prompt appearance of the non-vanishing free OH stretching band upon resonant photoionization of the pi-bound neutral clusters, and the delayed appearance of the hydrogen-bonded (H bonded) OH stretching band. This result directly proves that the Rg ligand switches from the pi-bound site on the aromatic ring to the H-bonded site at the OH group by ionization. The subsequent H ->pi back reaction converges the dimer to a pi<-> H equilibrium. This result is in sharp contrast to the single-step pi > H forward reaction in the PhOH(+)-Ar2 trimer with 100% yield. The reaction mechanism and yield strongly depend on intracluster vibrational energy redistribution. A classical rate equation analysis for the time evolutions of the band intensities of the two vibrations results in similar estimates for the time constants of the pi-> H forward reaction of tau+ = 122 and 73 ps and the H ->pi back reaction of tau- = 155 and 188 ps for PhOH(+)-Ar and PhOH(+)-Kr, respectively. The one order of magnitude slower time constant in comparison to the PhOH(+)-Ar2 trimer (tau+ = 7 ps) is attributed to the decrease in density of states due to the absence of the second Ar in the dimer. The similar time constants for both PhOH(+)-Rg dimers are well rationalized by a classical interpretation based on the comparable potential energy surfaces, reaction pathways, and density of states arising from their similar intermolecular vibrational frequencies. PMID- 27550721 TI - Yield responses of wild C3 and C4 crop progenitors to subambient CO2 : a test for the role of CO2 limitation in the origin of agriculture. AB - Limitation of plant productivity by the low partial pressure of atmospheric CO2 (Ca ) experienced during the last glacial period is hypothesized to have been an important constraint on the origins of agriculture. In support of this hypothesis, previous work has shown that glacial Ca limits vegetative growth in the wild progenitors of both C3 and C4 founder crops. Here, we present data showing that glacial Ca also reduces grain yield in both crop types. We grew four wild progenitors of C3 (einkorn wheat and barley) and C4 crops (foxtail and broomcorn millets) at glacial and postglacial Ca , measuring grain yield and the morphological and physiological components contributing to these yield changes. The C3 species showed a significant increase in unthreshed grain yield of ~50% with the glacial to postglacial increase in Ca , which matched the stimulation of photosynthesis, suggesting that increases in photosynthesis are directly translated into yield at subambient levels of Ca . Increased yield was controlled by a higher rate of tillering, leading to a larger number of tillers bearing fertile spikes, and increases in seed number and size. The C4 species showed smaller, but significant, increases in grain yield of 10-15%, arising from larger seed numbers and sizes. Photosynthesis was enhanced by Ca in only one C4 species and the effect diminished during development, suggesting that an indirect mechanism mediated by plant water relations could also be playing a role in the yield increase. Interestingly, the C4 species at glacial Ca showed some evidence that photosynthetic capacity was upregulated to enhance carbon capture. Development under glacial Ca also impacted negatively on the subsequent germination and viability of seeds. These results suggest that the grain production of both C3 and C4 crop progenitors was limited by the atmospheric conditions of the last glacial period, with important implications for the origins of agriculture. PMID- 27550722 TI - Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection. AB - BACKGROUND: The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. METHODS: Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. RESULTS: Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7.8 per cent (20 of 256) in the IV-only group and 7.8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0.017). There were no differences in rates of incisional site infection (5.5 versus 5.9 per cent respectively), organ/space infection (2.3 versus 2.0 per cent) or other secondary endpoints between the two groups. CONCLUSION: Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 ( http://www.umin.ac.jp/ctr/). PMID- 27550724 TI - Molecular and ionic-scale chemical mechanisms behind the role of nitrocyl group in the electrochemical removal of heavy metals from sludge. AB - The chemical basis for improved removal rates of toxic heavy metals such as Zn and Cu from wastewater secondary sludge has been demonstrated in this study. Instead of using excess corrosive chemicals as the source of free nitrous acid (FNA) for improved solubility of heavy metals in the sludge (in order to enhance electrokinetics), an optimized use of aqua regia has been proposed as an alternative. Fragments of nitrocyl group originated from aqua regia are responsible for the disruption of biogenic mixed liquor volatile suspended solids (MLVSS) and this disruption resulted in enhanced removal of exposed and oxidized metal ions. A diversity of nitric oxide (NO), peroxy nitrous acid, and peroxy nitroso group are expected to be introduced in the mixed liquor by the aqua regia for enhanced electrochemical treatment. The effects of pectin as a post treatment on the Zn removal from sludge were also presented for the first time. Results revealed 63.6% Cu and 93.7% Zn removal efficiencies, as compared to 49% Cu and 74% Zn removal efficiencies reported in a recent study. Also, 93.3% reduction of time-to-filter (TTF), and 95 mL/g of sludge volume index (SVI) were reported. The total operating cost obtained was USD 1.972/wet ton. PMID- 27550723 TI - The Abuse Intervention Model: A Pragmatic Approach to Intervention for Elder Mistreatment. AB - Ten percent of older adults experience elder mistreatment, and it is much more common in older adults with dementia. It is associated with higher rates of psychological distress, hospitalization, and death and, in the United States, costs billions of dollars each year. Although elder mistreatment is relatively common and costly, it is estimated that fewer than 10% of instances of elder mistreatment are reported. Given these data, there is a great need for research on interventions to mitigate elder mistreatment and for a practical model or framework to use in approaching such interventions. Although many theories have been proposed, adapted, and applied to understand elder mistreatment, there has not been a simple, coherent framework of known risk factors of the victim, perpetrator, and environment that applies to all types of abuse. This article presents a new model to examine the multidimensional and complex relationships between risk factors. Theories of elder mistreatment, research on risk factors for elder mistreatment, and 10 years of experience of faculty and staff at an Elder Abuse Forensics Center who have investigated more than 1,000 cases of elder mistreatment inform this model. It is hoped that this model, the Abuse Intervention Model, will be used to study and intervene in elder mistreatment. PMID- 27550725 TI - Maternal creatine in pregnancy: a retrospective cohort study. AB - OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each MUmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations. PMID- 27550726 TI - The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis. AB - The ability to resist the killing effects of host antimicrobial peptides (AMPs) plays a vital role in the virulence of pathogens. The Brucella melitensis NI genome has a gene cluster that encodes ABC transport. In this study, we constructed yejA1, yejA2, yejB, yejE, yejF, and whole yej operon deletion mutants, none of which exhibited discernible growth defect in TSB or minimal medium. Unlike their parental strain, the mutants showed a significantly increased sensitivity to acidic stress. The NIDeltayejE and NIDeltayejABEF mutants were also more sensitive than B. melitensis NI to polymyxin B, and the expression of yej operon genes was induced by polymyxin B. Moreover, cell and mouse infection assays indicated that NIDeltayejE and NIDeltayejABEF have restricted invasion and replication abilities inside macrophages and are rapidly cleared from the spleens of infected mice. These findings indicate that the ABC transporter YejABEF is required for the virulence of Brucella, suggesting that resistance to host antimicrobials is a key mechanism for Brucella to persistently survive in vivo. This study provided insights that led us to further investigate the potential correlation of AMP resistance with the mechanisms of immune escape and persistent infection by pathogens. PMID- 27550727 TI - Remote site hemorrhage after intracranial surgeries: is it really benign? PMID- 27550728 TI - Can Triglyceride to High-Density Lipoprotein Cholesterol Ratio Be an Independent Predictor of Cardiovascular Events in Patients With Essential Hypertension? PMID- 27550729 TI - Low microsatellites used to investigate leopard genetic structure severely restricts the results by Ropiquet et al. (2015) to infer population structure for managers. AB - Low microsatellites used to investigate leopard genetic structure severely restricts the results by Ropiquet et al. (2015) to infer population structure for managers. PMID- 27550731 TI - Garcinol: A Magic Bullet of Amnesia for Maladaptive Memories? PMID- 27550730 TI - A First-in-Class Small-Molecule that Acts as a Dual Inhibitor of HDAC and PDE5 and that Rescues Hippocampal Synaptic Impairment in Alzheimer's Disease Mice. AB - The targeting of two independent but synergistic enzymatic activities, histone deacetylases (HDACs, class I and HDAC6) and phosphodiesterase 5 (PDE5), has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). Here we report the discovery of a new first-in-class small-molecule (CM-414) that acts as a dual inhibitor of PDE5 and HDACs. We have used this compound as a chemical probe to validate this systems therapeutics strategy, where an increase in the activation of cAMP/cGMP-responsive element binding protein (CREB) induced by PDE5 inhibition, combined with moderate HDAC class I inhibition, leads to efficient histone acetylation. This molecule rescued the impaired long-term potentiation evident in hippocampal slices from APP/PS1 mice. Chronic treatment of Tg2576 mice with CM-414 diminished brain Abeta and tau phosphorylation (pTau) levels, increased the inactive form of GSK3beta, reverted the decrease in dendritic spine density on hippocampal neurons, and reversed their cognitive deficits, at least in part by inducing the expression of genes related to synaptic transmission. Thus, CM-414 may serve as the starting point to discover balanced dual inhibitors with an optimal efficacy and safety profile for clinical testing on AD patients. PMID- 27550732 TI - Lisdexamfetamine Effects on Executive Activation and Neurochemistry in Menopausal Women with Executive Function Difficulties. AB - Many women with no history of executive dysfunction report difficulties in this domain during the menopause transition. Lisdexamfetamine (LDX) has been suggested to be a safe and effective treatment option for these women. However, the mechanism by which LDX improves executive functioning in these women is not known. Here we investigated the effects of LDX on brain activation and neurochemistry, hypothesizing that LDX would be associated with increased activation and decreased glutamate in executive regions. Fourteen women underwent multimodal neuroimaging at 7T at three time points in this baseline-corrected, double-blind, placebo-controlled, crossover study. Effects of LDX on symptom severity, blood-oxygen-level-dependent (BOLD) signal, and dorsolateral prefrontal cortex (DLPFC) glutamate+glutamine (Glx) were measured using a clinician administered questionnaire, fMRI during performance of a fractal n-back task, and 1H-MRS, respectively. The effect of treatment (LDX minus baseline vs placebo minus baseline) on these behavioral and neural markers of executive function was examined using repeated measures mixed effects models. LDX treatment was associated with decreased symptom severity, increased activation in the insula and DLPFC, and decreased DLPFC Glx. In addition, the magnitude of LDX-induced improvement in symptom severity predicted both direction and magnitude of LDX induced change in insular and DLPFC activation. Moreover, symptom severity was positively correlated with Glx concentration in the left DLPFC at baseline. These findings provide novel evidence that the neural mechanisms by which LDX acts to improve self-reported executive functioning in healthy menopausal women with midlife onset of executive difficulties include modulation of insular and DLPFC recruitment as well as decrease in DLPFC Glx concentration. PMID- 27550735 TI - Racial disparities in cervical length for prediction of preterm birth in a low risk population. AB - PURPOSE: Racial minorities experience higher rates of spontaneous preterm birth (sPTB). Our objective was to evaluate whether there are racial discrepancies in the incidence of second trimester short cervical length (<=25 mm). MATERIALS AND METHODS: Retrospective cohort of women with singleton gestations without prior sPTB undergoing universal second trimester transvaginal ultrasound cervical length (CL) screening between January 2012 and December 2013. Black women were compared to non-Hispanic white women. Our primary outcome was the incidence of CL <=25 mm. Secondary outcomes were incidence of PTB <=37 weeks, delivery mode, birth weight and neonatal intensive care unit (NICU) admission. RESULTS: Black women (n = 1092) differed from non-Hispanic white women (n = 659) with respect to maternal age (26.0 versus 30.7 years), gravidity (3.1 versus 2.1), prepregnancy BMI (29.6 versus 25.0 kg/m2), and smoking status (9.8% versus 16%), respectively (p < 0.001). Black women had higher incidence of CL <=25 mm (1.9% versus 0.6%; OR: 3.21 [1.1-9.4]), rates of sPTB (8.5% versus 4.4%; aOR: 1.95 [1.1-3.4]), incidence of low birthweight infants (<2500 g, 8.3% versus 5.6%; aOR 1.80 [1.1 3.0]) and were more likely to have their infants admitted to the NICU (16% versus 11%; OR: 1.52 [1.0-2.3]). CONCLUSIONS: Black women had a 2.8-fold increased risk of CL <=25 mm compared non-Hispanic white women in a low-risk population. PMID- 27550736 TI - Eye movement programming and reading accuracy. AB - Eye movements were measured during the silent reading of sentences to extract several oculomotor measures. Rather than each measure being examined independently, oculomotor responses were grouped into two types, the assumption being that the grouping would project onto underlying constructs. Properties of forward-directed movements were assumed to reflect the success with which linguistic information was acquired (acquisition), and corrective responses were assumed to reveal readers' responding to difficulties (correction). These two types of oculomotor responses were linked to indexes of reading accuracy (accuracy), which were obtained from separate materials so that eye movements with one set of materials could be used to predict reading accuracy for another set of materials. Path analyses indicated that correction, but not acquisition, was linked to accuracy. The additional clustering of acquisition, correction, and accuracy scores identified a group of readers with relatively low accuracy scores. These readers were typical in their acquisition of linguistic information but under-used corrective responding. PMID- 27550733 TI - Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment. AB - Biomarker, neuroimaging, and genetic findings implicate the serotonin transporter (SERT) in autism spectrum disorder (ASD). Previously, we found that adult male mice expressing the autism-associated SERT Ala56 variant have altered central serotonin (5-HT) system function, as well as elevated peripheral blood 5-HT levels. Early in gestation, before midbrain 5-HT projections have reached the cortex, peripheral sources supply 5-HT to the forebrain, suggesting that altered maternal or placenta 5-HT system function could impact the developing embryo. We therefore used different combinations of maternal and embryo SERT Ala56 genotypes to examine effects on blood, placenta and embryo serotonin levels and neurodevelopment at embryonic day E14.5, when peripheral sources of 5-HT predominate, and E18.5, when midbrain 5-HT projections have reached the forebrain. Maternal SERT Ala56 genotype was associated with decreased placenta and embryonic forebrain 5-HT levels at E14.5. Low 5-HT in the placenta persisted, but forebrain levels normalized by E18.5. Maternal SERT Ala56 genotype effects on forebrain 5-HT levels were accompanied by a broadening of 5-HT-sensitive thalamocortical axon projections. In contrast, no effect of embryo genotype was seen in concepti from heterozygous dams. Blood 5-HT levels were dynamic across pregnancy and were increased in SERT Ala56 dams at E14.5. Placenta RNA sequencing data at E14.5 indicated substantial impact of maternal SERT Ala56 genotype, with alterations in immune and metabolic-related pathways. Collectively, these findings indicate that maternal SERT function impacts offspring placental 5-HT levels, forebrain 5-HT levels, and neurodevelopment. PMID- 27550737 TI - Controlled Synthesis of Pt Nanowires with Ordered Large Mesopores for Methanol Oxidation Reaction. AB - Catalysts for methanol oxidation reaction (MOR) are at the heart of key green energy fuel cell technology. Nanostructured Pt materials are the most popular and effective catalysts for MOR. Controlling the morphology and structure of Pt nanomaterials can provide opportunities to greatly increase their activity and stability. Ordered nanoporous Pt nanowires with controlled large mesopores (15, 30 and 45 nm) are facilely fabricated by chemical reduction deposition from dual templates using porous anodic aluminum oxide (AAO) membranes with silica nanospheres self-assembled in the channels. The prepared mesoporous Pt nanowires are highly active and stable electrocatalysts for MOR. The mesoporous Pt nanowires with 15 nm mesopores exhibit a large electrochemically active surface area (ECSA, 40.5 m(2) g(-1)), a high mass activity (398 mA mg(-1)) and specific activity (0.98 mA cm(-2)), and a good If/Ib ratio (1.15), better than the other mesoporous Pt nanowires and the commercial Pt black catalyst. PMID- 27550734 TI - Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra. AB - The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n=13) and matched controls (n=12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n=4) or on medication (n=9); or (2) treatment response: treatment resistant (n=5) or treatment responsive (n=4). The combined schizophrenia group had higher TH and GAD67 protein levels than controls (an increase of 69.6%, P=0.01 and 19.5%, P=0.004, respectively). When subdivided by medication status, these increases were found in the on medication subjects (TH 88.3%, P=0.008; GAD67 40.6%, P=0.003). In contrast, unmedicated schizophrenia subjects had higher vGLUT2 levels than controls (an increase of 28.7%, P=0.041), but vGLUT2 levels were similar between medicated schizophrenia subjects and controls. Treatment-resistant subjects had significantly higher TH and GAD67 levels than controls (an increase of 121.0%, P=0.0003 and 58.7%, P=0.004, respectively). These data suggest increases in dopamine and GABA transmission in the SN in schizophrenia, with a potential relation to treatment and response. PMID- 27550738 TI - Cell-to-cell communication in guided bone regeneration: molecular and cellular mechanisms. AB - This overview provides insights into the molecular and cellular mechanisms involved in guided bone regeneration, in particular focusing on aspects presented in the 3D movie, Cell-To-Cell Communication in Guided Bone Regeneration. The information presented here is based almost exclusively on genetic mouse models in which single genes can be deleted or overexpressed, even in a specific cell type. This information needs to be extrapolated to humans and related to aspects relevant to graft consolidation under the clinical parameters of guided bone regeneration. The overview follows the ground tenor of the Cell-To-Cell Communication series and focuses on aspects of cell-to-cell communication in bone regeneration and guided bone regeneration. Here, we discuss (1) the role of inflammation during bone regeneration, including (2) the importance of the fibrin matrix, and (3) the pleiotropic functions of macrophages. We highlight (4) the origin of bone-forming osteoblasts and bone-resorbing osteoclasts as well as (5) what causes a progenitor cell to mature into an effector cell. (6) We touch on the complex bone adaptation and maintenance after graft consolidation and (7) how osteocytes control this process. Finally, we speculate on (8) how barrier membranes and the augmentation material can modulate graft consolidation. PMID- 27550739 TI - Creating opportunities for interdisciplinary collaboration and patient-centred care: how nurses, doctors, pharmacists and patients use communication strategies when managing medications in an acute hospital setting. AB - AIMS AND OBJECTIVES: This paper examines the communication strategies that nurses, doctors, pharmacists and patients use when managing medications. BACKGROUND: Patient-centred medication management is best accomplished through interdisciplinary practice. Effective communication about managing medications between clinicians and patients has a direct influence on patient outcomes. There is a lack of research that adopts a multidisciplinary approach and involves critical in-depth analysis of medication interactions among nurses, doctors, pharmacists and patients. DESIGN: A critical ethnographic approach with video reflexivity was adopted to capture communication strategies during medication activities in two general medical wards of an acute care hospital in Melbourne, Australia. METHODS: A mixed ethnographic approach combining participant observations, field interviews, video recordings and video reflexive focus groups and interviews was employed. Seventy-six nurses, 31 doctors, 1 pharmacist and 27 patients gave written consent to participate in the study. Data analysis was informed by Fairclough's critical discourse analytic framework. FINDINGS: Clinicians' use of communication strategies was demonstrated in their interpersonal, authoritative and instructive talk with patients. Doctors adopted the language discourse of normalisation to standardise patients' illness experiences. Nurses and pharmacists employed the language discourses of preparedness and scrutiny to ensure that patient safety was maintained. Patients took up the discourse of politeness to raise medication concerns and question treatment decisions made by doctors, in their attempts to challenge decision making about their health care treatment. In addition, the video method revealed clinicians' extensive use of body language in communication processes for medication management. CONCLUSIONS: The use of communication strategies by nurses, doctors, pharmacists and patients created opportunities for improved interdisciplinary collaboration and patient-centred medication management in an acute hospital setting. Language discourses shaped and were shaped by complex power relations between patients and clinicians and among clinicians themselves. RELEVANCE TO CLINICAL PRACTICE: Clinicians need to be encouraged to have regular conversations to talk about and challenge each other's practices. More emphasis should be placed on ensuring that patients are given opportunities to voice their concerns about how their medications are managed. PMID- 27550740 TI - Surface freezing and surface coverage as key factors for spontaneous formation of colloidal fibers in vacuum drying of colloidal suspensions. AB - In this study, we investigated vacuum drying of droplets of colloidal suspension. Because of the loss of the latent heat of vaporization, the drying droplet was cooled and then formed ice. Colloidal fibers consisting of packed particles spontaneously formed when the droplet froze from the gas-liquid interface. Conversely, we observed formation of sponge-like porous structures of particles when the whole droplet almost simultaneously froze. However, the freezing mode was not the only factor for formation of colloidal fibers. We found that the surface coverage of particles on the gas-liquid interface was also important. Owing to drying, some particles accumulated at the interface before freezing. When the surface coverage was higher than a threshold value, formation of fibers was severely restricted even in the surface freezing mode. Our results clearly show the important roles of surface freezing and the surface coverage of particles on the gas-liquid interface in formation of colloidal fibers. PMID- 27550742 TI - Interactions of Lipidic Cubic Phase Nanoparticles with Lipid Membranes. AB - The interactions of liquid-crystalline monoolein (GMO) cubic phase nanoparticles with various model lipid membranes spread at the air-solution interface by the Langmuir technique were investigated. Cubosomes have attracted attention as potential biocompatible drug delivery systems, and thus understanding their mode of interaction with membranes is of special interest. Cubosomes spreading at the air-water interface as well as interactions with a monolayer of 1, 2-dipalmitoyl sn-glycero-3-phosphocholine (DPPC) compressed to different surface pressures were studied by monitoring surface pressure-time dependencies at constant area. Progressive incorporation of the nanoparticles was shown to lead to mixed monolayer formation. The concentration of cubosomes influenced the mechanism of incorporation, as well as the fluidity and permeability of the resulting lipid membranes. Brewster angle microscopy images reflected the dependence of the monolayer structure on the cubosomes presence in the subphase. A parameter Csat was introduced to indicate the point of saturation of the lipid membrane with the cubosomal material. This parameter was found to depend on the surface pressure showing that the cubosomes disintegrate in prolonged contact with the membrane, filling available voids in the lipid membrane. At highest surface pressures when the layer is most compact, the penetration of cubosomal material is not possible and only some exchange with the membrane lipid becomes the route of including GMO into the layer. Finally, comparative studies of the interactions between lipids with various headgroup charges with cubosomes suggest that at high surface pressure an exchange of lipid component between the monolayer and the cubosome in its intact form may occur. PMID- 27550741 TI - Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease. AB - Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease like damage in rodent disease models and considered in clinical association studies in PD. PMID- 27550743 TI - Concentric Circular Grating Generated by the Patterning Trapping of Nanoparticles in an Optofluidic Chip. AB - Due to the field enhancement effect of the hollow-core metal-cladded optical waveguide chip, massive nanoparticles in a solvent are effectively trapped via exciting ultrahigh order modes. A concentric ring structure of the trapped nanoparticles is obtained since the excited modes are omnidirectional at small incident angle. During the process of solvent evaporation, the nanoparticles remain well trapped since the excitation condition of the optical modes is still valid, and a concentric circular grating consisting of deposited nanoparticles can be produced by this approach. Experiments via scanning electron microscopy, atomic force microscopy and diffraction of a probe laser confirmed the above hypothesis. This technique provides an alternative strategy to enable effective trapping of dielectric particles with low-intensity nonfocused illumination, and a better understanding of the correlation between the guided modes in an optical waveguide and the nanoparticles in a solvent. PMID- 27550744 TI - Nonthermal Plasma Synthesis of Nanocrystals: Fundamental Principles, Materials, and Applications. AB - Nonthermal plasmas have emerged as a viable synthesis technique for nanocrystal materials. Inherently solvent and ligand-free, nonthermal plasmas offer the ability to synthesize high purity nanocrystals of materials that require high synthesis temperatures. The nonequilibrium environment in nonthermal plasmas has a number of attractive attributes: energetic surface reactions selectively heat the nanoparticles to temperatures that can strongly exceed the gas temperature; charging of nanoparticles through plasma electrons reduces or eliminates nanoparticle agglomeration; and the large difference between the chemical potentials of the gaseous growth species and the species bound to the nanoparticle surfaces facilitates nanocrystal doping. This paper reviews the state of the art in nonthermal plasma synthesis of nanocrystals. It discusses the fundamentals of nanocrystal formation in plasmas, reviews practical implementations of plasma reactors, surveys the materials that have been produced with nonthermal plasmas and surface chemistries that have been developed, and provides an overview of applications of plasma-synthesized nanocrystals. PMID- 27550745 TI - Factors influencing sialocele or salivary fistula formation postparotidectomy. AB - BACKGROUND: Does the extent of parotidectomy or other patient or tumor characteristics influence the rate of sialocele/salivary fistula formation? METHODS: All patients who underwent parotidectomy at the University of Wisconsin from 1994 to 2013 were considered. Patients who developed a sialocele/salivary fistula were identified. Extent of dissection, age, sex, body mass index (BMI), volume of specimen, and rate of malignancy were examined. RESULTS: Seventy of 771 patients (9.1%) developed a sialocele/salivary fistula. Sixty-seven fistulae (96%) developed within 1 month and all resolved by 6 months. Age, sex, pathology, and BMI were not increased in the sialocele group. Inferior and middle superficial parotidectomy had a significantly higher rate of sialocele than other extents of dissection. Volume of tissue removed was not significantly different between dissection groups. CONCLUSION: Sialocele/salivary fistula is common postparotidectomy and is more likely with inferior and middle superficial parotidectomy. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 387-391, 2017. PMID- 27550746 TI - Computerised attention training for children with intellectual and developmental disabilities: a randomised controlled trial. AB - BACKGROUND: Children with intellectual and developmental disabilities (IDD) experience heightened attention difficulties which have been linked to poorer cognitive, academic and social outcomes. Although, increasing research has focused on the potential of computerised cognitive training in reducing attention problems, limited studies have assessed whether this intervention could be utilised for those with IDD. This study aimed to assess the efficacy of a computerised attention training programme in children with IDD. METHODS: In a double-blind randomised controlled trial, children (n = 76; IQ < 75) aged 4-11 years were assigned to an adaptive attention training condition or a nonadaptive control condition. Both conditions were completed at home over a 5-week period and consisted of 25 sessions, each of 20-min duration. Outcome measures (baseline, posttraining and 3-month follow-up) assessed core attention skills (selective attention, sustained attention and attentional control) and inattentive/hyperactive behaviour. RESULTS: Children in the attention training condition showed greater improvement in selective attention performance compared to children in the control condition (SMD = 0.24, 95% CI 0.02, 0.45). These improvements were maintained 3 months after training had ceased (SMD = 0.26, 95% CI 0.04, 0.48). The attention training programme was not effective in promoting improvements in sustained attention, attentional control or inattentive/hyperactive behaviours. CONCLUSIONS: The findings suggest that attention training may enhance some aspects of attention (selective attention) in children with IDD, but the small to medium effect sizes indicate that further refinement of the training programme is needed to promote larger, more global improvements. PMID- 27550747 TI - Suicidality and its determinants among Polish patients with epilepsy. AB - BACKGROUND AND PURPOSE: The aim of this study was to evaluate the prevalence of suicidal ideation among Polish patients with epilepsy and to assess the potential determinants of suicidality in this cohort. MATERIAL AND METHODS: The study comprised 301 patients with epilepsy seen in the tertiary epilepsy clinic. Patients' characteristics included demographic variables, epilepsy-related variables, as well as occurrence of comorbidities, ongoing use of any other medications, family history of epilepsy and/or depression. Beck Depression Inventory (BDI) was used to assess depressive symptoms, and question no. 9 of BDI was specifically used to reveal suicidality. RESULTS: Mean age of subjects was 35.5 years. 113 (37.5%) had frequent seizures and 96 patients (31.9%) had remission. BDI score>11 points (suggestive for depression) was found in 127 subjects. Suicidal ideation has been revealed in 30 (10.0%) out of 301 studied patients. Patients with suicidal ideation were older and more commonly reported frequent seizures. Almost all of them (93.3%) had clinically significant depressive symptoms (BDI score>11). Multivariate analysis revealed that severity of depressive symptoms (OR=1.16 per one-point increase in BDI score, 95% CI: 1.10 1.22, p<0.001) and the use of potentially depressogenic medication (OR=3.04, 95% CI: 1.04-8.89, p=0.04) were independent determinants of suicidality among studied patients. CONCLUSIONS: Suicidal ideations were revealed by about 10% of studied epileptic patients who visited tertiary center for epilepsy. Independent predictors of suicidality among studied patients included depression itself and the use of potentially depressogenic medication. PMID- 27550748 TI - New roles for CD14 and IL-beta linking inflammatory dendritic cells to IL-17 production in memory CD4+ T cells. AB - Interleukin (IL)-1beta has proven to be crucial in the differentiation of human and mouse Th17 cells. Although it has become evident that IL-1beta has potent IL 17-inducing effects on CD4+ T cells directly, it has not yet been explored whether IL-1beta can also prime dendritic cells (DCs) for a Th17 instruction program. Here, we show that human immature DCs exposed to IL-1beta promote IL-17 production in human memory CD4+ T cells. IL-1beta-primed DCs express high levels of CD14 that mediate IL-17 production through direct interaction with T cells. Moreover, culturing human CD4+CD45RO+ memory T cells with soluble CD14 is sufficient for the upregulation of retinoic acid-related orphan receptor-gamma thymus and IL-17 production. In addition, in a human in situ model using tissue resident skin DCs, upregulation of CD14 expression induced by IL-1beta on skin residents DCs promotes IL-17 production in memory T cells; strongly suggesting the in vivo relevance of this mechanism. Our findings uncover new roles for IL 1beta and CD14, and may therefore have important consequences for the development of new therapies for Th17-mediated autoimmune diseases and bacterial and fungal pathogenic infections. PMID- 27550751 TI - Effect of Primary Care Involvement on End-of-Life Care Outcomes: A Systematic Review. AB - OBJECTIVES: To investigate the relationship between primary care involvement in end-of-life (EOL) care and health and utilization outcomes. DESIGN: Systematic review using MEDLINE and Web of Science. SETTING: All English literature published between 1994 and August 31, 2014, that included terms related to primary care providers (PCPs), continuity of care, EOL care, and palliative care. PARTICIPANTS: Individuals receiving care from a PCP at the end of life. MEASUREMENTS: Study design, subject characteristics, study outcomes and results. RESULTS: Of 2,812 studies screened, 13 were included in this study. The studies were mostly conducted in the United States (n = 5) and Canada (n = 4) and analyzed data collected from 1989 to 2010. Almost all studies used different definitions of PCP involvement in care, but in general, individuals who received more care from PCPs were more likely to be discharged or die with supportive care (home or hospice) than those receiving less PCP care. A few studies indicated that individuals seeing a PCP were less likely to have hospital or emergency department admissions, although the evidence for this was mixed. Studies linking PCP involvement to resource use, symptom management, and survival had mixed results or showed no association. CONCLUSION: When PCPs are involved in EOL care, people are more likely to die out of the hospital. Thus, the relationship with the PCP may be particularly important in EOL care, because PCPs may help individual establish goals of care and determine treatment preferences. PMID- 27550750 TI - Traditional Breast Cancer Risk Factors in Filipina Americans Compared with Chinese and Japanese Americans in Los Angeles County. AB - BACKGROUND: Filipina Americans have one of the highest breast cancer incidence rates among Asian Americans for poorly understood reasons. METHODS: Breast cancer risk factors were investigated in a population-based study of Filipina (790 cases, 587 controls), Japanese (543 cases, 510 controls), and Chinese (913 cases, 904 controls) Americans. Cases were identified by the Los Angeles County Cancer Surveillance Program, and controls were matched to cases on age, ethnicity, and neighborhood. Multivariable conditional logistic regression was performed by Asian ethnicity. RESULTS: In Filipina, Chinese, and Japanese Americans, breast cancer risk decreased significantly with increasing parity (all Ptrend < 0.0001). Breast cancer risk increased with increasing quartiles of cumulative menstrual months in premenopausal (Ptrend = 0.019) and postmenopausal Filipina (Ptrend = 0.008), in premenopausal (Ptrend = 0.0003) but not postmenopausal Chinese (Ptrend = 0.79), and in neither premenopausal (Ptrend = 0.092) nor postmenopausal (Ptrend = 0.75) Japanese Americans. For postmenopausal Filipina and Japanese, greater weight gain since age 18 (Ptrend = 0.019 and 0.053, respectively), high current body mass index (both Ptrend < 0.01), and greater waist circumferences (both Ptrend < 0.04) were statistically significant; these associations were weaker for postmenopausal Chinese women. CONCLUSIONS: Cumulative menstrual months and body size factors were statistically significant risk factors for Filipina. Total menstrual months were associated with breast cancer among Chinese but not for Japanese, while body size factors were significantly associated with risk among Japanese but not among Chinese. IMPACT: Characterization of breast cancer risk factors in Filipina will help to generate hypotheses for their high breast cancer incidence. Cancer Epidemiol Biomarkers Prev; 25(12); 1572-86. (c)2016 AACR. PMID- 27550752 TI - Inputs to prefrontal cortex support visual recognition in the aging brain. AB - Predictive coding models of brain function propose that top-down cortical signals promote efficient neural codes by carrying predictions of upcoming sensory events. We hypothesized that older brains would employ these codes more prominently given their longer repertoire of sensory experience. We measured the connectivity underlying stimulus-evoked responses in cortical visual networks using electroencephalography and dynamic causal modeling and found that in young adults with reported normal or corrected-to-normal vision, signals propagated from early visual regions and reverberated along reciprocal connections to temporal, parietal and frontal cortices, while in contrast, the network was driven by both early visual and prefrontal inputs in older adults with reported normal or corrected-to-normal vision. Previously thought of as exceptions to the rule of bottom-up signal propagation, our results demonstrate a prominent role for prefrontal inputs in driving vision in aged brains in line with lifespan dependent predictive neural codes. PMID- 27550754 TI - Validation of the alternating conditional estimation algorithm for estimation of flexible extensions of Cox's proportional hazards model with nonlinear constraints on the parameters. AB - Standard optimization algorithms for maximizing likelihood may not be applicable to the estimation of those flexible multivariable models that are nonlinear in their parameters. For applications where the model's structure permits separating estimation of mutually exclusive subsets of parameters into distinct steps, we propose the alternating conditional estimation (ACE) algorithm. We validate the algorithm, in simulations, for estimation of two flexible extensions of Cox's proportional hazards model where the standard maximum partial likelihood estimation does not apply, with simultaneous modeling of (1) nonlinear and time dependent effects of continuous covariates on the hazard, and (2) nonlinear interaction and main effects of the same variable. We also apply the algorithm in real-life analyses to estimate nonlinear and time-dependent effects of prognostic factors for mortality in colon cancer. Analyses of both simulated and real-life data illustrate good statistical properties of the ACE algorithm and its ability to yield new potentially useful insights about the data structure. PMID- 27550749 TI - Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer. AB - BACKGROUND: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. METHODS: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. RESULTS: The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 * 10-17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44-1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10-1.39; P = 5.3 * 10-4). There was evidence of directional pleiotropy (P = 1.5 * 10-4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 * 10-4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. CONCLUSIONS: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. IMPACT: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503-10. (c)2016 AACR. PMID- 27550755 TI - Unpacking religious affiliation: Exploring associations between Christian children's religious cultural context, God image, and self-esteem across development. AB - In developmental research, religiousness is typically measured with omnibus affiliation or attendance variables that underspecify how the religious cultural contexts and experiences that affiliation represents influence developmental outcomes. This study explores associations between five aspects of a religious cultural context (family religiosity, religious schooling, church-based relationships with peers and adults, and view of God) in 844 seven- to 12-year old Christian children to examine how they differentially predict self-esteem. Results of a structural equation model (SEM) analysis indicated that God image and peer church relationships directly predicted self-esteem, whereas God image mediated the influence of adult church relationships and family religious practices on self-esteem. A multiple group SEM analysis met the criterion for weak, but not strong, evidence that self-esteem is more related to younger children's adult church relationships but older children's peer church relationships. God image tended to be more related to younger children's family religious practices but older children's adult church relationships. Implications for developmental researchers and practitioners are discussed. Statement of contribution What is already known on this subject? Religious affiliation is an omnibus variable representing multiple contexts of development. Self-esteem is an important outcome variable with different influences across development. Religious affiliation is associated with increased self-esteem. What does this study add? Children's experience in the contexts of religious affiliation influences development differently. It is not just affiliation, but specific religious contexts that influence children's self-esteem. The role of religious contexts in shaping children's self-esteem shifts across development. PMID- 27550756 TI - Terrestrial atmospheric responses on Svalbard to the 20 March 2015 Arctic total solar eclipse under extreme conditions. AB - This article reports on the near-surface atmospheric response at the High Arctic site of Svalbard, latitude 78 degrees N, as a result of abrupt changes in solar insolation during the 20 March 2015 equinox total solar eclipse and notifies the atmospheric science community of the availability of a rare dataset. Svalbard was central in the path of totality, and had completely clear skies. Measurements of shaded air temperature and atmospheric pressure show only weak, if any, responses to the reduced insolation. A minimum in the air temperature at 1.5 m above the ground occurred starting 2 min following the end of totality, though this drop was only slightly beyond the observed variability for the midday period. Eclipse produced variations in surface pressure, if present, were less than 0.3 hPa.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550757 TI - Coordinated weather balloon solar radiation measurements during a solar eclipse. AB - Solar eclipses provide a rapidly changing solar radiation environment. These changes can be studied using simple photodiode sensors, if the radiation reaching the sensors is unaffected by cloud. Transporting the sensors aloft using standard meteorological instrument packages modified to carry extra sensors, provides one promising but hitherto unexploited possibility for making solar eclipse radiation measurements. For the 20 March 2015 solar eclipse, a coordinated campaign of balloon-carried solar radiation measurements was undertaken from Reading (51.44 degrees N, 0.94 degrees W), Lerwick (60.15 degrees N, 1.13 degrees W) and Reykjavik (64.13 degrees N, 21.90 degrees W), straddling the path of the eclipse. The balloons reached sufficient altitude at the eclipse time for eclipse-induced variations in solar radiation and solar limb darkening to be measured above cloud. Because the sensor platforms were free to swing, techniques have been evaluated to correct the measurements for their changing orientation. In the swing-averaged technique, the mean value across a set of swings was used to approximate the radiation falling on a horizontal surface; in the swing-maximum technique, the direct beam was estimated by assuming that the maximum solar radiation during a swing occurs when the photodiode sensing surface becomes normal to the direction of the solar beam. Both approaches, essentially independent, give values that agree with theoretical expectations for the eclipse induced radiation changes.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550758 TI - Symbolism and discovery: eclipses in art. AB - There is a fascinating tradition of depicting solar eclipses in Western art, although these representations have changed over time. Eclipses have often been an important feature of Christian iconography, but valued as much for their biblical significance as for the splendour of the physical event. However, as Western culture passed through the Renaissance and Enlightenment the depictions of eclipses came to reflect new astronomical knowledge and a thirst for rational learning well beyond the confines of the church and other elites. Artists also played a surprisingly important role in helping scientists in the nineteenth century understand and record the full phenomena of an eclipse, even as the advent of photography also came to solve a number of scientific puzzles. In the most recent century, artists have responded to eclipses with symbolism, abstraction and playfulness.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550759 TI - Eclipse-induced wind changes over the British Isles on the 20 March 2015. AB - The British Isles benefits from dense meteorological observation networks, enabling insights into the still-unresolved effects of solar eclipse events on the near-surface wind field. The near-surface effects of the solar eclipse of 20 March 2015 are derived through comparison of output from the Met Office's operational weather forecast model (which is ignorant of the eclipse) with data from two meteorological networks: the Met Office's land surface station (MIDAS) network and a roadside measurement network operated by Vaisala. Synoptic evolution relative calculations reveal the cooling and increase in relative humidity almost universally attributed to eclipse events. In addition, a slackening of wind speeds by up to about 2 knots in already weak winds and backing in wind direction of about 20 degrees under clear skies across middle England are attributed to the eclipse event. The slackening of wind speed is consistent with the previously reported boundary layer stabilization during eclipse events. Wind direction changes have previously been attributed to a large scale 'eclipse-induced cold-cored cyclone', mountain slope flows, and changes in the strength of sea breezes. A new explanation is proposed here by analogy with nocturnal wind changes at sunset and shown to predict direction changes consistent with those observed.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550760 TI - Atmospheric changes from solar eclipses. AB - This article reviews atmospheric changes associated with 44 solar eclipses, beginning with the first quantitative results available, from 1834 (earlier qualitative accounts also exist). Eclipse meteorology attracted relatively few publications until the total solar eclipse of 16 February 1980, with the 11 August 1999 eclipse producing the most papers. Eclipses passing over populated areas such as Europe, China and India now regularly attract scientific attention, whereas atmospheric measurements of eclipses at remote locations remain rare. Many measurements and models have been used to exploit the uniquely predictable solar forcing provided by an eclipse. In this paper, we compile the available publications and review a subset of them chosen on the basis of importance and novelty. Beyond the obvious reduction in incoming solar radiation, atmospheric cooling from eclipses can induce dynamical changes. Observations and meteorological modelling provide evidence for the generation of a local eclipse circulation that may be the origin of the 'eclipse wind'. Gravity waves set up by the eclipse can, in principle, be detected as atmospheric pressure fluctuations, though theoretical predictions are limited, and many of the data are inconclusive. Eclipse events providing important early insights into the ionization of the upper atmosphere are also briefly reviewed.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550761 TI - The National Eclipse Weather Experiment: use and evaluation of a citizen science tool for schools outreach. AB - The National Eclipse Weather Experiment (NEWEx) was a citizen science project for atmospheric data collection from the partial solar eclipse of 20 March 20. Its role as a tool for schools outreach is discussed here, in seeking to bridge the gap between self-identification with the role of a scientist and engagement with science, technology, engineering and mathematics subjects. (The science data generated have had other uses beyond this, explored elsewhere.) We describe the design of webforms for weather data collection, and the use of several external partners for the dissemination of the project nationwide. We estimate that up to 3500 pupils and teachers took part in this experiment, through the 127 schools postcodes identified in the data submission. Further analysis revealed that 43.3% of the schools were primary schools and 35.4% were secondary. In total, 96.3% of participants reported themselves as 'captivated' or 'inspired' by NEWEx. We also found that 60% of the schools that took part in the experiment lie within the highest quintiles of engagement with higher education, which emphasizes the need for the scientific community to be creative when using citizen science projects to target hard-to-reach audiences.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550762 TI - Meteorological responses in the atmospheric boundary layer over southern England to the deep partial eclipse of 20 March 2015. AB - A wide range of surface and near-surface meteorological observations were made at the University of Reading's Atmospheric Observatory in central southern England (latitude 51.441 degrees N, longitude 0.938 degrees W, altitude 66 m above mean sea level) during the deep partial eclipse on the morning of 20 March 2015. Observations of temperature, humidity, radiation, wind speed and direction, and atmospheric pressure were made by computerized logging equipment at 1 Hz, supplemented by an automated cloud base recorder sampling at 1 min intervals and a high-resolution (approx. 10 m vertical interval) atmospheric sounding by radiosonde launched from the same location during the eclipse. Sources and details of each instrumental measurement are described briefly, followed by a summary of observed and derived measurements by meteorological parameter. Atmospheric boundary layer responses to the solar eclipse were muted owing to the heavily overcast conditions which prevailed at the observing location, but instrumental records of the event documented a large (approx. 80%) reduction in global solar radiation, a fall in air temperature of around 0.6 degrees C, a decrease in cloud base height, and a slight increase in atmospheric stability during the eclipse. Changes in surface atmospheric moisture content and barometric pressure were largely insignificant during the event.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550763 TI - On the detection and attribution of gravity waves generated by the 20 March 2015 solar eclipse. AB - Internal gravity waves are generated as adjustment radiation whenever a sudden change in forcing causes the atmosphere to depart from its large-scale balanced state. Such a forcing anomaly occurs during a solar eclipse, when the Moon's shadow cools part of the Earth's surface. The resulting atmospheric gravity waves are associated with pressure and temperature perturbations, which in principle are detectable both at the surface and aloft. In this study, surface pressure and temperature data from two UK sites at Reading and Lerwick are examined for eclipse-driven gravity wave perturbations during the 20 March 2015 solar eclipse over northwest Europe. Radiosonde wind data from the same two sites are also analysed using a moving parcel analysis method, to determine the periodicities of the waves aloft. On this occasion, the perturbations both at the surface and aloft are found not to be confidently attributable to eclipse-driven gravity waves. We conclude that the complex synoptic weather conditions over the UK at the time of this particular eclipse helped to mask any eclipse-driven gravity waves.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550764 TI - Satellite observations of surface temperature during the March 2015 total solar eclipse. AB - The behaviour of remotely sensed land surface temperatures (LSTs) from the spinning-enhanced visible and infrared imager (SEVIRI) during the total solar eclipse of 20 March 2015 is analysed over Europe. LST is found to drop by up to several degrees Celcius during the eclipse, with the minimum LST occurring just after the eclipse mid-point (median=+1.5 min). The drop in LST is typically larger than the drop in near-surface air temperatures reported elsewhere, and correlates with solar obscuration (r=-0.47; larger obscuration = larger LST drop), eclipse duration (r=-0.62; longer duration = larger LST drop) and time (r=+0.37; earlier eclipse = larger LST drop). Locally, the LST drop is also correlated with vegetation (up to r=+0.6), with smaller LST drops occurring over more vegetated surfaces. The LSTs at locations near the coast and at higher elevation are also less affected by the eclipse. This study covers the largest area and uses the most observations of eclipse-induced surface temperature drops to date, and is the first full characterization of satellite LST during an eclipse (known to the author). The methods described could be applied to Geostationary Operational Environmental Satellite (GOES) LST data over North America during the August 2017 total solar eclipse.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550765 TI - On the variability of near-surface screen temperature anomalies in the 20 March 2015 solar eclipse. AB - Near-surface air temperature (NSAT) anomalies during the 20 March 2015 solar eclipse are investigated at 266 UK sites, using operational data. The high density of observing sites, together with the wide range of ambient meteorological conditions, provided an unprecedented opportunity for analysis of the spatial variability of NSAT anomalies under relatively uniform eclipse conditions. Anomalies ranged from -0.03 degrees C to -4.23 degrees C (median 1.02 degrees C). The maximum (negative) anomaly lagged the maximum obscuration by 15 min on average. Cloud cover impacted strongly on NSAT anomalies, with larger anomalies in clear-sky situations (p<0.0001). Weaker, but statistically significant, correlations were found with wind speed (larger anomalies in weaker winds), proximity to coast (larger anomalies at inland sites), topography (larger anomalies in topographical low points) and land cover (larger anomalies over vegetated surfaces). In this mid-morning eclipse, the topographical influences on NSAT anomalies were apparently dominated by variations in residual nocturnal inversion strength, as suggested by significant correlations between post-sunrise temperature and NSAT anomaly at clear-sky sites (larger negative anomalies with lower post-sunrise temperatures). The largest NSAT anomaly occurred at a coastal site where flow transitioned from onshore to offshore during the eclipse, in a situation with large coastal temperature gradients associated with antecedent nocturnal cooling.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550766 TI - Using the ionospheric response to the solar eclipse on 20 March 2015 to detect spatial structure in the solar corona. AB - The total solar eclipse that occurred over the Arctic region on 20 March 2015 was seen as a partial eclipse over much of Europe. Observations of this eclipse were used to investigate the high time resolution (1 min) decay and recovery of the Earth's ionospheric E-region above the ionospheric monitoring station in Chilton, UK. At the altitude of this region (100 km), the maximum phase of the eclipse was 88.88% obscuration of the photosphere occurring at 9:29:41.5 UT. In comparison, the ionospheric response revealed a maximum obscuration of 66% (leaving a fraction, Phi, of uneclipsed radiation of 34+/-4%) occurring at 9:29 UT. The eclipse was re-created using data from the Solar Dynamics Observatory to estimate the fraction of radiation incident on the Earth's atmosphere throughout the eclipse from nine different emission wavelengths in the extreme ultraviolet (EUV) and X-ray spectrum. These emissions, having varying spatial distributions, were each obscured differently during the eclipse. Those wavelengths associated with coronal emissions (94, 211 and 335 A) most closely reproduced the time varying fraction of unobscured radiation observed in the ionosphere. These results could enable historic ionospheric eclipse measurements to be interpreted in terms of the distribution of EUV and X-ray emissions on the solar disc.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550767 TI - The National Eclipse Weather Experiment: an assessment of citizen scientist weather observations. AB - The National Eclipse Weather Experiment (NEWEx) was a citizen science project designed to assess the effects of the 20 March 2015 partial solar eclipse on the weather over the United Kingdom (UK). NEWEx had two principal objectives: to provide a spatial network of meteorological observations across the UK to aid the investigation of eclipse-induced weather changes, and to develop a nationwide public engagement activity-based participation of citizen scientists. In total, NEWEx collected 15 606 observations of air temperature, cloudiness and wind speed and direction from 309 locations across the UK, over a 3 h window spanning the eclipse period. The headline results were processed in near real time, immediately published online, and featured in UK national press articles on the day of the eclipse. Here, we describe the technical development of NEWEx and how the observations provided by the citizen scientists were analysed. By comparing the results of the NEWEx analyses with results from other investigations of the same eclipse using different observational networks, including measurements from the University of Reading's Atmospheric Observatory, we demonstrate that NEWEx provided a fair representation of the change in the UK meteorological conditions throughout the eclipse. Despite the simplicity of the approach adopted, robust reductions in both temperature and wind speed during the eclipse were observed.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550768 TI - The solar eclipse: a natural meteorological experiment. AB - A solar eclipse provides a well-characterized reduction in solar radiation, of calculable amount and duration. This captivating natural astronomical phenomenon is ideally suited to science outreach activities, but the predictability of the change in solar radiation also provides unusual conditions for assessing the atmospheric response to a known stimulus. Modern automatic observing networks used for weather forecasting and atmospheric research have dense spatial coverage, so the quantitative meteorological responses to an eclipse can now be evaluated with excellent space and time resolution. Numerical models representing the atmosphere at high spatial resolution can also be used to predict eclipse related changes and interpret the observations. Combining the models with measurements yields the elements of a controlled atmospheric experiment on a regional scale (10-1000 km), which is almost impossible to achieve by other means. This modern approach to 'eclipse meteorology' as identified here can ultimately improve weather prediction models and be used to plan for transient reductions in renewable electricity generation. During the 20 March 2015 eclipse, UK electrical energy demand increased by about 3 GWh (11 TJ) or about 4%, alongside reductions in the wind and photovoltaic electrical energy generation of 1.5 GWh (5.5 TJ).This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550769 TI - Meteorological effects of the solar eclipse of 20 March 2015: analysis of UK Met Office automatic weather station data and comparison with automatic weather station data from the Faroes and Iceland. AB - Here, we analyse high-frequency (1 min) surface air temperature, mean sea-level pressure (MSLP), wind speed and direction and cloud-cover data acquired during the solar eclipse of 20 March 2015 from 76 UK Met Office weather stations, and compare the results with those from 30 weather stations in the Faroe Islands and 148 stations in Iceland. There was a statistically significant mean UK temperature drop of 0.83+/-0.63 degrees C, which occurred over 39 min on average, and the minimum temperature lagged the peak of the eclipse by about 10 min. For a subset of 14 (16) relatively clear (cloudy) stations, the mean temperature drop was 0.91+/-0.78 (0.31+/-0.40) degrees C but the mean temperature drops for relatively calm and windy stations were almost identical. Mean wind speed dropped significantly by 9% on average during the first half of the eclipse. There was no discernible effect of the eclipse on the wind-direction or MSLP time series, and therefore we can discount any localized eclipse cyclone effect over Britain during this event. Similar changes in air temperature and wind speed are observed for Iceland, where conditions were generally clearer, but here too there was no evidence of an eclipse cyclone; in the Faroes, there was a much more muted meteorological signature.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550770 TI - Numerical simulations of the impact of the 20 March 2015 eclipse on UK weather. AB - Short lead-time forecasts using the operational United Kingdom variable resolution (UKV) configuration of the Met Office's numerical weather prediction model, with horizontal grid-length 1.5 km over the UK, with and without a representation of the 20 March 2015 eclipse, have been used to simulate the impact of the eclipse on UK weather. The major impact was surface-driven through changes to surface heat and moisture fluxes that changed the boundary-layer development. In cloud-free areas, the nocturnal stable boundary layer persisted or quickly re-established during the eclipse. Surface temperatures were reduced by 7-8 degrees C, near-surface air temperature by 1-3 degrees C, and near-surface winds were backed, typically by 20 degrees . Impacts on wind speed were small and variable, and would have been very difficult to detect. Smaller impacts occurred beneath cloud. However, the impact was enhanced because most of the incoming radiation that reached the surface was driving surface sensible heat flux rather than moisture flux, and the near-surface air temperature impact (0.5-1 degrees C) agrees reasonably well with observations. The modelled impact of the eclipse was substantially reduced in urban areas due to their large thermal inertia. Experience from other assessments of the model suggests that this lack of response may be exaggerated. Surface impacts propagated upwards and downstream with time, resulting in a complex pattern of response, though generally near surface temperature differences persisted for many hours after the eclipse. The impact on atmospheric pressure fields was insufficient to account for any significant perturbations to the wind field when compared with the direct impacts of surface stress and boundary-layer mixing.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550771 TI - Effects of the March 2015 solar eclipse on near-surface atmospheric electricity. AB - Measurements of atmospheric electrical and standard meteorological parameters were made at coastal and inland sites in southern England during the 20 March 2015 partial solar eclipse. Clear evidence of a reduction in air temperature resulting from the eclipse was found at both locations, despite one of them being overcast during the entire eclipse. The reduction in temperature was expected to affect the near-surface electric field (potential gradient (PG)) through a reduction in turbulent transfer of space charge. No such effect could be unambiguously confirmed, however, with variability in PG and air-Earth current during the eclipse being comparable to pre- and post-eclipse conditions. The already low solar radiation for this latitude, season and time of day was likely to have contributed to the reduced effect of the eclipse on atmospheric electricity through boundary layer stability. The absence of a reduction in mean PG shortly after time of maximum solar obscuration, as observed during eclipses at lower geomagnetic latitude, implied that there was no significant change in atmospheric ionization from cosmic rays above background variability. This finding was suggested to be due to the relative importance of cosmic rays of solar and galactic origin at geomagnetic mid-latitudes.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'. PMID- 27550772 TI - D6h -Au42 Isomer: A Golden Aromatic Toroid Involving Superatomic pi-Orbitals that Follow the Huckel (4n+2)pi rule. AB - Recently, it has been shown that the superatom concept is intimately connected to relevant tools of great chemical significance, such as the Lewis structure model and the VSEPR theory, which has been employed to understand hybridized and dimeric-like molecules. This suggests a potential rational construction of superatomic clusters mimicking more complex structures. Here, we extend another well-employed concept to the superatomic clusters, to construct a novel Au42 isomer with resemblance to cyclic aromatic molecules. It is shown that the Huckel (4n+2)pi rule is ready to be applied, predicting aromatic behavior latterly supported by the favorable evaluation of the induced shielding cone formation. The D6 h isomer of Au42 described here exhibits inherent characteristics mimicking aromatic hydrocarbon rings, displaying pi-superatomic orbitals and related properties. This new cluster is the first member of the superatomic clusters family to exhibit an aromatic pi-electron system. PMID- 27550773 TI - Metabolic Syndrome Patients Have Lower Levels of Adropin When Compared With Healthy Overweight/Obese and Lean Subjects. AB - Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, is a challenging public health issue. The aim of current study was to test the hypothesis that concentrations of plasma adropin and leptin differ between patients with MetS and comparable age- and sex-matched control groups. This case control study involved 153 subjects (51 per group). The study group included obese subjects with MetS and the two control groups included weight-matched subjects without MetS ("healthy": obese) and normal weight subjects without MetS. Body composition parameters were measured using bioelectrical impedance analysis. Plasma levels of adropin, leptin, and their ratio were measured. Leptin was significantly different between obese patients with/without MetS groups and normal weight subjects. Patients with MetS had higher levels of leptin (14 +/- 12.4) compared with those without MetS (11.2 +/- 9.3 vs. 7 +/- 7.1 obese and normal weight without MetS, respectively; p = .002). Compared with healthy obese and normal weight subjects, MetS subjects had lower levels of plasma adropin ( p < .001) and a lower plasma adropin to leptin ratio ( p < .001), which remained significant when adjusted for body fat mass by analysis of covariance ( p < .001). This study demonstrates low levels of adropin are correlated with MetS and hence identify it as a potentially protective agent against MetS development. Variation in adropin levels may partly explain the "healthy obese" phenomenon. PMID- 27550774 TI - Exploring Experiences and Perceptions of Older African American Males Aging With HIV in the Rural Southern United States. AB - The HIV (human immunodeficiency virus) epidemic in the United States remains a serious public health concern. Despite treatment and prevention efforts, approximately 50,000 new HIV cases are transmitted each year. Estimates indicate that 44% of all people diagnosed with HIV are living in the southern region of the United States. African Americans represent 13.2% of the United States population; however, 44% (19,540) of reported new HIV cases in 2014 were diagnosed within this ethnic group. The majority of cases were diagnosed in men (73%, 14,305). In the United States, it is estimated that 21% of adults living with HIV are 50 years or older. There exists limited data regarding how well African American men are aging with HIV disease. The purpose of this study was to explore the perceptions and experiences of older African American men living with HIV in rural Georgia. Data were collected from 35 older African American men living with HIV using focus groups and face-to-face personal interviews. Qualitative content analysis revealed six overlapping themes: (1) Stigma; (2) Doing Fine, Most of the Time; (3) Coping With Age-Related Diseases and HIV; (4) Self-Care; (5) Family Support; and (6) Access to Resources. The findings from this study provide new insights into the lives of rural HIV-infected African American men, expands our understanding of how they manage the disease, and why many return to or remain in rural communities. PMID- 27550775 TI - Evaluation of CROES Nephrolithometry Nomogram as a Preoperative Predictive System for Percutaneous Nephrolithotomy Outcomes. AB - PURPOSE: Scoring systems have been devised to predict outcomes of percutaneous nephrolithotomy (PCNL). CROES nephrolithometry nomogram (CNN) is the latest tool devised to predict stone-free rate (SFR). We aim to compare predictive accuracy of CNN against Guy stone score (GSS) for SFR and postoperative outcomes. MATERIALS AND METHODS: Between January 2013 and December 2015, 313 patients undergoing PCNL were analyzed for predictive accuracy of GSS, CNN, and stone burden (SB) for SFR, complications, operation time (OT), and length of hospitalization (LOH). We further stratified patients into risk groups based on CNN and GSS. RESULTS: Mean +/- standard deviation (SD) SB was 298.8 +/- 235.75 mm2. SB, GSS, and CNN (area under curve [AUC]: 0.662, 0.660, 0.673) were found to be predictors of SFR. However, predictability for complications was not as good (AUC: SB 0.583, GSS 0.554, CNN 0.580). Single implicated calix (Adj. OR 3.644; p = 0.027), absence of staghorn calculus (Adj. OR 3.091; p = 0.044), single stone (Adj. OR 3.855; p = 0.002), and single puncture (Adj. OR 2.309; p = 0.048) significantly predicted SFR on multivariate analysis. Charlson comorbidity index (CCI; p = 0.020) and staghorn calculus (p = 0.002) were independent predictors for complications on linear regression. SB and GSS independently predicted OT on multivariate analysis. SB and complications significantly predicted LOH, while GSS and CNN did not predict LOH. CNN offered better risk stratification for residual stones than GSS. CONCLUSION: CNN and GSS have good preoperative predictive accuracy for SFR. Number of implicated calices may affect SFR, and CCI affects complications. Studies should incorporate these factors in scoring systems and assess if predictability of PCNL outcomes improves. PMID- 27550777 TI - Effect of Applying Force to Self-Adhesive Electrodes on Transthoracic Impedance: Implications for Electrical Cardioversion. AB - BACKGROUND: Current guidelines disagree on the role for applying force to electrodes during electrical cardioversion (ECV) for atrial fibrillation, particularly when using self-adhesive pads. We evaluated the impact of this practice on transthoracic impedance (TTI) with varying force and in individuals with differing body mass indices (BMI). We additionally assessed whether specific prompts could improve physicians' ECV technique. METHODS: The study comprised three parts: (1) TTI was measured in 11 participants throughout the respiratory cycle and with variable force applied to self-adhesive electrodes in anteroposterior (AP) and anterolateral (AL) configurations. (2) Three participants in different BMI classes then had TTI measured with prespecified incremental force applied. (3) Ten blinded cardiology trainees simulated ECV on one participant with and without prompting (guideline reminders and force analogies) while force applied and TTI were measured. RESULTS: The AP approach was associated with 13% lower TTI than AL (P < 0.001). Strongly negative correlations were observed between force applied and TTI in the AL position, irrespective of BMI (P <= 0.003). In all cases, 80% of the total reduction in TTI observed was achieved with 8 kg-force (~80 N). All prompts resulted in significantly greater force applied and modest reductions in TTI. CONCLUSIONS: Applying force to self-adhesive electrodes reduces TTI and should be considered as a means of improving ECV success. Numerically greater mean force applied with a "push-up" force analogy suggests that "concrete" cues may be useful in improving ECV technique. PMID- 27550776 TI - Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample. AB - Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds (NAAc, N acetylaspartate plus N-acetyl-aspartyl-glutamate), a marker of neuronal viability, can be quantified with proton magnetic resonance spectroscopy (1H MRS). We used 1H-MRS imaging to assess Glx and NAAc, as well as total-choline (glycerophospho-choline plus phospho-choline), myo-inositol and total-creatine (creatine plus phosphocreatine) from an axial supraventricular slab of gray matter (GM, medial-frontal and medial-parietal) and white matter (WM, bilateral frontal and bilateral-parietal) voxels. Schizophrenia subjects (N = 104) and healthy controls (N = 97) with a broad age range (16 to 65) were studied. In schizophrenia, Glx was increased in GM (P < .001) and WM (P = .01), regardless of age. However, with greater age, NAAc increased in GM (P < .001) but decreased in WM (P < .001) in schizophrenia. In patients, total creatine decreased with age in WM (P < .001). Finally, overall cognitive score correlated positively with WM neurometabolites in controls but negatively in the schizophrenia group (NAAc, P < .001; and creatine [only younger], P < .001). We speculate the results support an ongoing process of increased glutamate metabolism in schizophrenia. Later in the illness, disease progression is suggested by increased cortical compaction without neuronal loss (elevated NAAc) and reduced axonal integrity (lower NAAc). Furthermore, this process is associated with fundamentally altered relationships between neurometabolite concentrations and cognitive function in schizophrenia. PMID- 27550778 TI - Right-sided endocarditis: eustachian valve and coronary sinus involvement. AB - Infective endocarditis in patients with intravenous drug use commonly involves right-sided heart valves. Eustachian valve (EV) endocarditis is not commonly seen given the valve's infrequent presence. Involvement of the coronary sinus (CS) with endocarditis is also an unusual finding. We present a case with echocardiographic findings consistent with EV endocarditis along with CS involvement, which appropriately responded to antibiotics. PMID- 27550779 TI - Characterizing Si:P quantum dot qubits with spin resonance techniques. AB - Quantum dots patterned by atomically precise placement of phosphorus donors in single crystal silicon have long spin lifetimes, advantages in addressability, large exchange tunability, and are readily available few-electron systems. To be utilized as quantum bits, it is important to non-invasively characterise these donor quantum dots post fabrication and extract the number of bound electron and nuclear spins as well as their locations. Here, we propose a metrology technique based on electron spin resonance (ESR) measurements with the on-chip circuitry already needed for qubit manipulation to obtain atomic scale information about donor quantum dots and their spin configurations. Using atomistic tight-binding technique and Hartree self-consistent field approximation, we show that the ESR transition frequencies are directly related to the number of donors, electrons, and their locations through the electron-nuclear hyperfine interaction. PMID- 27550780 TI - Identification of types of landings after blocking in volleyball associated with risk of ACL injury. AB - Landing with a low knee flexion angle after volleyball block jumps may be associated with an increased risk of anterior cruciate ligament (ACL) injury. The aim of the present study was to identify the types of volleyball landings after blocks where the knee flexion angle is found to be under a critical knee flexion angle value of 30 degrees at the instant of the first peak of the ground reaction force (GRF). Synchronized kinematic and kinetic data were collected for each trial. T-tests were used to determine if each knee flexion angle at the instant of the peak GRF was significantly different from the critical value of 30 degrees . A repeated measures ANOVA was used to compare knee flexion angle, time to first peak and the magnitude of the first peak of the resultant GRF and knee stiffness. Significantly lower knee flexion angles were found in the "go" landing (p = .01, ES = 0.6) and the "reverse" landing (p = .02, ES = 0.6) only. The results for knee flexion angle and GRF parameters indicated a significant difference between a "reverse" and "go" and other types of landings, except the "side stick" landing for GRF. The "reverse" and "go" landings may present a risk for ACL injury due to the single-leg landing of these activities that have an associated mediolateral movement. PMID- 27550782 TI - Resolution of nodulocystic acne with oral dapsone. PMID- 27550781 TI - Trends in all-cause five-year mortality after head and neck cancers diagnosed over a period of 33 years. Focus on estimated degree of association with human papillomavirus. AB - BACKGROUND: Factors influencing survival after head and neck cancer (HNC) include among others stage, age, and sex. More recently, human papillomavirus (HPV) positivity has been described as a favorable prognostic factor in relation to some HNCs. MATERIAL AND METHODS: In this nationwide register-based cohort study of all 20 925 individuals diagnosed with squamous cell carcinoma of the head and neck (HNSCC) in Denmark 1978-2010, we investigate secular trends in all-cause five-year mortality after HNSCC according to the anticipated degree of association with HPV using a Cox proportional hazards model. Furthermore, we examine whether any trend over time differed according to sex, stage, and age at diagnosis. RESULTS: All-cause five-year mortality after HNSCC has decreased over time. The greatest decrease was seen in the last decade (2000-2010) among patients with HNSCC at sites estimated to be strongly associated with HPV, i.e. the base of the tongue and the tonsils, where a 28% decrease per five years (e.g. HRbase of tongue/tonsils=0.72; 95% CI 0.64-0.81) was observed. When examining sex and age-specific time trends, the decrease in mortality was most pronounced among male patients and patients below 60 years at diagnosis. In contrast, no clear pattern was observed when examining five-year all-cause mortality trends according to stage. CONCLUSION: All-cause five-year mortality after HNSCC has decreased significantly in Denmark from 1978 to 2010, especially for HNSCCs at sites anticipated to be strongly associated with HPV, possibly due to an increasing proportion of HPV-positive HNSCCs. PMID- 27550783 TI - [Mobile applications for management of Type 2 diabetes]. AB - This literature review describes Type 2 diabetes applications with regard to purpose, effect, preferences and possibilities. Diabetes apps might have a positive effect on the health of a person with diabetes. Some studies have found improve-ments in HbA1c, body weight and health behaviour. Important is to personalise diabetes apps to the target group and involve the group actively in the development and testing of the app. More research on how diabetes apps can be implemented in the healthcare system is crucial. Current research is characterised by methodological challenges. PMID- 27550784 TI - [Immune checkpoint antibodies increase survival in patients with metastatic melanoma]. AB - The incidence of melanoma is rising and until recently, metastatic melanoma had a poor survival prognosis. Manipulation of two newly discovered immune pathways have shown impressive results. The first is treatment with anti-cytotoxic T lymphocyte-antigen (CTLA)-4 antibody which blocks the inhibitory receptor CTLA-4. The other is anti-programmed cell death (PD)-1 antibody which blocks the inhibitory receptor PD-1 on T-cells. Thereby, the T-cells are kept activated and able to attack cancer cells. PMID- 27550785 TI - [Treatment of constipation in palliative care patients is a challenge]. AB - The evidence for treatment of constipation in palliative care patients is poor. The condition of these patients is often complex, and results from studies performed in other patient groups cannot be extrapolated unconditionally. However, macrogol (polyethylene glycol), lactulose and sodium picosulphate seem to be well tolerated, and methylnaltrexone could be used in opioid-induced constipation, if the patients are not at risk from gastrointestinal perforation. The patients should be offered quiet and private surroundings, and attention should be payed to securing an optimal body position for defecation. PMID- 27550786 TI - [Stenafstobning af kateterspids ved Proteus mirabilis-infektion]. PMID- 27550787 TI - The impact of stratification by implausible energy reporting status on estimates of diet-health relationships. AB - The food frequency questionnaire (FFQ) is known to be prone to measurement error. Researchers have suggested excluding implausible energy reporters (IERs) of FFQ total energy when examining the relationship between a health outcome and FFQ reported intake to obtain less biased estimates of the effect of the error-prone measure of exposure; however, the statistical properties of stratifying by IER status have not been studied. Under certain assumptions, including nondifferential error, we show that when stratifying by IER status, the attenuation of the estimated relative risk in the stratified models will be either greater or less in both strata (implausible and plausible reporters) than for the nonstratified model, contrary to the common belief that the attenuation will be less among plausible reporters and greater among IERs. Whether there is more or less attenuation depends on the pairwise correlations between true exposure, observed exposure, and the stratification variable. Thus exclusion of IERs is inadvisable but stratification by IER status can sometimes help. We also address the case of differential error. Examples from the Observing Protein and Energy Nutrition Study and simulations illustrate these results. PMID- 27550788 TI - How to integrate quality improvement into GUM and HIV services. PMID- 27550789 TI - Building Materials from Colloidal Nanocrystal Arrays: Evolution of Structure, Composition, and Mechanical Properties upon the Removal of Ligands by O2 Plasma. AB - The mechanical properties of colloidal nanocrystal superlattices can be tailored through exposure to low-pressure plasma. The elastic modulus and hardness of the ligand-free 3.7 nm ZrO2 superlattice are found to be similar to bulk yttria stabilized tetragonal polycrystals of the same relative density but without any doping. PMID- 27550790 TI - Quantum dots protected from oxidative attack using alumina shells synthesized by atomic layer deposition. AB - Applications of luminescent quantum dots require the materials to be stable under a wide range of temperatures, photon fluxes and chemical environments. In this work, we demonstrate that Al2O3 shells synthesized by atomic layer deposition on films of CdTe quantum dots are effective to prevent chemical degradation for up to 17 hours under continuous illumination at 90 degrees C in ambient air. Control samples with no Al2O3 coating experienced extensive oxidation and severe quenching of the photoluminescence intensity under these conditions. PMID- 27550791 TI - Proteomic profiling of human plasma for cancer biomarker discovery. AB - Over the past decades, substantial advances have been made in both the early diagnosis and accurate prognosis of many cancers because of the impressive development of novel proteomic strategies. However, it remains difficult to standardize proteomic approaches. In addition, the heterogeneity of proteins in distinct tissues results in incomplete population of the whole proteome, which inevitably limits its clinical practice. As one of the most complex proteomes in the human body, the plasma proteome contains secreted proteins originating from multiple organs and tissues, making it a favorable matrix for comprehensive biomarker discovery. Here, we will discuss the roles of plasma proteome profiling in cancer biomarker discovery and validation, and highlight both the inherent advantages and disadvantages. Although several hurdles lay ahead, further advances in this technology will greatly increase our understanding of cancer biology, reveal new biomarkers and biomarker panels, and open a new avenue for more efficient early diagnosis and surveillance of cancer, leading toward personalized medicine. PMID- 27550793 TI - The photochemistry of sodium ion pump rhodopsin observed by watermarked femto- to submillisecond stimulated Raman spectroscopy. AB - Krokinobacter rhodopsin 2 (KR2) is a recently discovered light-driven Na(+) pump that holds significant promise for application as a neural silencer in optogenetics. KR2 transports Na(+) (in NaCl solution) or H(+) (in larger cation solution, e.g. in CsCl) during its photocycle. Here, we investigate the photochemistry of KR2 with the recently developed watermarked, baseline-free femto- to submillisecond transient stimulated Raman spectroscopy (TSRS), which enables us to investigate retinal chromophore dynamics in real time with high spectral resolution over a large time range. We propose a new photocycle from femtoseconds to submilliseconds: J (formed in ~200 fs) -> K (~3 ps) -> K/L1 (~20 ps) -> K/L2 (~30 ns) -> L/M (~20 MUs). KR2 binds a Na(+) ion that is not transported on the extracellular side, of which the function is unclear. We demonstrate with TSRS that for the D102N mutant in NaCl (with Na(+) unbound, Na(+) transport) and for WT KR2 in CsCl (with Na(+) unbound, H(+) transport), the extracellular Na(+) binding significantly influences the intermediate K/L/M state equilibrium on the photocycle, while the identity of the transported ion, Na(+) or H(+), does not affect the photocycle. Our findings will contribute to further elucidation of the molecular mechanisms of KR2. PMID- 27550792 TI - Self-administration of injectable contraceptives: a systematic review. AB - BACKGROUND: The contraceptive injectable is a safe and effective method that is used worldwide. With the variety of injectable delivery systems, there is potential for administration by the woman herself. Self-administration of the contraceptive injectable is the subject of this systematic review. OBJECTIVES: To assess how effective and safe the contraceptive injectable method is when women themselves perform/administer it, compared with when the usual healthcare providers administer it. SEARCH STRATEGY: We searched PubMed, Popline, Cochrane, CINAHL, and Embase for articles with subject headings or text words related to 'self-administration' and 'contraception'. SELECTION CRITERIA: Studies that compared the administration of the contraceptive injectable by the woman herself versus administration by the healthcare provider were included. Outcomes of interest were continuation rates, safety, and the women's overall satisfaction with the contraceptive provider and method. DATA COLLECTION AND ANALYSIS: We undertook data extraction, descriptive analysis, and assessment of risk of bias. MAIN RESULTS: Three studies met the inclusion criteria. The best available evidence shows that there may be little or no difference in continuation rates when women self-administer contraceptive injections (326 per 1000 women; 95% CI 192-554 per 1000 women) compared with administration by healthcare providers (304 per 1000 women). Safety was not estimable as no serious adverse events were reported in any of the studies. With regards to overall satisfaction towards the provider and the method, the effect of the intervention was uncertain. AUTHORS' CONCLUSIONS: Findings suggest that with appropriate information and training the provision of contraceptive injectables for the woman to self-administer at home can be an option in some contexts. TWEETABLE ABSTRACT: This review assessed the continuation rates and safety of self-administration of the contraceptive injection. PMID- 27550794 TI - Asymmetry in inward- and outward-affinity constant of transport explain unidirectional lysine flux in Saccharomyces cerevisiae. AB - The import of basic amino acids in Saccharomyces cerevisiae has been reported to be unidirectional, which is not typical of how secondary transporters work. Since studies of energy coupling and transport kinetics are complicated in vivo, we purified the major lysine transporter (Lyp1) of yeast and reconstituted the protein into lipid vesicles. We show that the Michaelis constant (KM) of transport from out-to-in is well in the millimolar range and at least 3 to 4 orders of magnitude higher than that of transport in the opposite direction, disfavoring the efflux of solute via Lyp1. We also find that at low values of the proton motive force, the transport by Lyp1 is comparatively slow. We benchmarked the properties of eukaryotic Lyp1 to that of the prokaryotic homologue LysP and find that LysP has a similar KM for transport from in-to-out and out-to-in, consistent with rapid influx and efflux. We thus explain the previously described unidirectional nature of lysine transport in S. cerevisiae by the extraordinary kinetics of Lyp1 and provide a mechanism and rationale for previous observations. The high asymmetry in transport together with secondary storage in the vacuole allow the cell to accumulate basic amino acids to very high levels. PMID- 27550795 TI - Increased discriminability of authenticity from multimodal laughter is driven by auditory information. AB - We present an investigation of the perception of authenticity in audiovisual laughter, in which we contrast spontaneous and volitional samples and examine the contributions of unimodal affective information to multimodal percepts. In a pilot study, we demonstrate that listeners perceive spontaneous laughs as more authentic than volitional ones, both in unimodal (audio-only, visual-only) and multimodal contexts (audiovisual). In the main experiment, we show that the discriminability of volitional and spontaneous laughter is enhanced for multimodal laughter. Analyses of relationships between affective ratings and the perception of authenticity show that, while both unimodal percepts significantly predict evaluations of audiovisual laughter, it is auditory affective cues that have the greater influence on multimodal percepts. We discuss differences and potential mismatches in emotion signalling through voices and faces, in the context of spontaneous and volitional behaviour, and highlight issues that should be addressed in future studies of dynamic multimodal emotion processing. PMID- 27550799 TI - Identifying the essential components of cultural competence in a Chinese nursing context: A qualitative study. AB - This qualitative study using semi-structured interviews was conducted to identify the essential components of cultural competence from the perspective of Chinese nurses. A purposive sample of 20 nurse experts, including senior clinical nurses, nurse administrators, and educators in transcultural nursing, was recruited. Using thematic analysis, four themes: awareness, attitudes, knowledge, and skills, with two subthemes for each, were identified. Notably, culture in China was understood in a broad way. The participants' responses focused upon demographic attributes, individuality, and efforts to facilitate quality care rather than on the cultural differences of ethnicity and race and developing the capacity to change discrimination or health disparities. A greater understanding of cultural competence in the Chinese nursing context, in which a dominant cultural group exists, is essential to facilitate the provision of culturally competent care to diverse populations. PMID- 27550796 TI - National study of the impact of patient information and involvement in decision making on immediate breast reconstruction rates. AB - BACKGROUND: Reconstructive alternatives should be discussed with women facing mastectomy for breast cancer. These include immediate and delayed reconstruction, which both have inherent advantages and disadvantages. Immediate reconstruction rates vary considerably in Swedish healthcare regions, and the aim of the study was to analyse reasons for this disparity. METHODS: All women who underwent mastectomy for primary breast cancer in Sweden in 2013 were included. Tumour data were retrieved from the Swedish National Breast Cancer Registry and from questionnaires regarding patient information and involvement in preoperative decision-making sent to women who were still alive in 2015. RESULTS: Of 2929 women who had undergone 2996 mastectomies, 2906 were still alive. The questionnaire response rate was 76.3 per cent. Immediate reconstruction rates varied regionally, between 3.0 and 26.4 per cent. Tumour characteristics impacted on reconstruction rates but did not explain regional differences. Patient participation in decision-making, availability of plastic surgery services and patient information, however, were independent predictors of immediate breast reconstruction, and varied significantly between regions. Even in younger patients with low-risk tumours, rates of patient information ranged between 34.3 and 83.3 per cent. CONCLUSION: Significant regional differences in immediate reconstruction rates were not explained by differences in tumour characteristics, but by disparities in patient information, availability of plastic surgery services and involvement in decision-making. PMID- 27550800 TI - Decatungstate acid improves the photo-induced electron lifetime and retards the recombination in dye sensitized solar cells. AB - Decatungstate acid (DA) was utilized to modify TiO2 in the photoanode of dye sensitized solar cells. The photo-induced electron lifetime was evidently improved and the recombination was greatly inhibited. DA can introduce levels of impurities and lower the Fermi level through a doping effect and thus increase the photocurrent. Moreover, the improved charge carrier density can be found through external electric field surface photovoltage and Mott-Schottky plots. A 22.94% enhancement in photocurrent was achieved with little degradation in photovoltage, leading to a 10.28% increase in optic-to-electric power conversion efficiency. PMID- 27550798 TI - High throughput cytotoxicity screening of anti-HER2 immunotoxins conjugated with antibody fragments from phage-displayed synthetic antibody libraries. AB - Immunotoxins are an important class of antibody-based therapeutics. The potency of the immunotoxins depends on the antibody fragments as the guiding modules targeting designated molecules on cell surfaces. Phage-displayed synthetic antibody scFv libraries provide abundant antibody fragment candidates as targeting modules for the immunoconjugates, but the discovery of optimally functional immunoconjugates is limited by the scFv-payload conjugation procedure. In this work, cytotoxicity screening of non-covalently assembled immunotoxins was developed in high throughput format to discover highly functional synthetic antibody fragments for delivering toxin payloads. The principles governing the efficiency of the antibodies as targeting modules have been elucidated from large volume of cytotoxicity data: (a) epitope and paratope of the antibody-based targeting module are major determinants for the potency of the immunotoxins; (b) immunotoxins with bivalent antibody-based targeting modules are generally superior in cytotoxic potency to those with corresponding monovalent targeting module; and (c) the potency of the immunotoxins is positively correlated with the densities of the cell surface antigen. These findings suggest that screening against the target cells with a large pool of antibodies from synthetic antibody libraries without the limitations of natural antibody responses can lead to optimal potency and minimal off-target toxicity of the immunoconjugates. PMID- 27550801 TI - Not Just Atypical Presentation, but Also Atypical Site: Tuberculosis in Elderly Adults. PMID- 27550802 TI - Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Associated with Myeloma and Syndrome of Inappropriate Antidiuretic Hormone Secretion in an Elderly Man. PMID- 27550803 TI - A novel fluorescence "on-off-on" chemosensor for Hg(2+)via a water-assistant blocking heavy atom effect. AB - Upper rim pyrene-functionalized hexahomotrioxacalix[3]arene L was synthesized via Click chemistry, and its fluorescence behaviors toward several common metal cations were investigated. L exhibited a significant fluorescence quenching response to Hg(2+) in CH3CN solution, which was unaffected by the coexistence of other competitive metal cations. Thus, L can be utilized as a highly selective and sensitive fluorescent chemosensor for Hg(2+) with a detection limit in the nM level. Interestingly, the quenched fluorescence emission can be successfully revived upon the addition of water. In this process, the heavy atom effect of Hg(2+) can be blocked by further coordination of a water molecule and resulted in the revival of the fluorescence emission of L/Hg(2+) complex. Particularly, other polar solvents such as CH3OH and CH3CH2OH also have the ability to revive the fluorescence emission of the L/Hg(2+) complex, but on a much smaller scale than observed for H2O. The heavy atom effect and blocking thereof were demonstrated within the same system by the use of a C3-symmetric homooxacalix[3]arene scaffold. The present studies provided further evidence for the blocking heavy atom effect. PMID- 27550804 TI - Changes in Characteristics and Practice Patterns of Ontario Psychiatrists. AB - OBJECTIVE: The objective of this study was to evaluate the changes in demographic, geographic, and practice characteristics of all Ontario psychiatrists between 2003 and 2013 and their implication for access to psychiatrists. METHODS: We included all psychiatrists who were clinically active in Ontario in any year from 2003 to 2013. For each psychiatrist, we reported age, sex, years since medical school graduation, geographic practice region, and practice characteristics such as total number of inpatients, outpatients, and outpatient visit frequencies. RESULTS: In 2013, there were 2070 psychiatrists, with nearly half (47%) more than 30 years since medical school graduation. Female psychiatrists comprised 41% of all psychiatrists in 2013 but 56% of all psychiatrists within 15 years of medical school graduation. Between 2003 and 2013, there was a 17% increase in the total number of psychiatrists, with the largest growth in psychiatrists occurring in the group more than 30 years from medical school graduation. Over these 11 years, the mean (SD) number of unique outpatients seen by a psychiatrist annually increased from 208 (228) to 249 (275) (19.5%; P = 0.001), with male psychiatrists, on average, seeing more outpatients annually than female psychiatrists. CONCLUSION: The number of outpatients seen by psychiatrists is slowly increasing. However, the large proportion of aging psychiatrists, the high concentration of psychiatrists in urban settings, and the increase in the number of female psychiatrists with smaller practices suggest that without radical changes to the way psychiatrists practice, access to psychiatrists will remain a challenge in Ontario. PMID- 27550805 TI - Analysis of Photoluminescence Thermal Quenching: Guidance for the Design of Highly Effective p-type Doping of Nitrides. AB - A contact-free diagnostic technique for examining position of the impurity energy level of p-type dopants in nitride semiconductors was proposed based on photoluminescence thermal quenching. The Mg ionization energy was extracted by the phenomenological rate-equation model we developed. The diagnostic technique and analysis model reported here are priorities for the design of highly effective p-doping of nitrides and could also be used to explain the abnormal and seldom analyzed low characteristic temperature T0 (about 100 K) of thermal quenching in p-type nitrides systems. An In-Mg co-doped GaN system is given as an example to prove the validity of our methods. Furthermore, a hole concentration as high as 1.94 * 10(18) cm(-3) was achieved through In-Mg co-doping, which is nearly one order of magnitude higher than typically obtained in our lab. PMID- 27550806 TI - A prospective population-based study, aiming to support decision-making in a follow-up programme for patients with cutaneous malignant melanoma, based on patterns of recurrence. AB - The incidence of malignant melanoma (MM) is steadily rising, with only a minor increase in mortality. At present, there is no consensus regarding recommendations for follow-up programmes for MM, and health care programmes currently involve different schedules. With increasing opportunities to administer successful treatment for early disseminated disease, it may be of interest to engage MM patients and/or relatives in self-control. The aim of the present study was to analyse both the time to, and the location of, the first metastatic lesion in order to provide help for the patient, relatives, and health professionals, and ensure better follow-up. Data from the Swedish Melanoma Register, pathology registers, and the Cause of Death Register were used. Patients from the south-east region diagnosed with primary cutaneous MM between 1993 and 2007 were selected and data were correlated to characteristics of the primary tumour. Metastases developed in 421 of the 2,910 patients with primary cutaneous MM in Stage I and II of the disease. Thirty-five percent of all recurrences were detected during the first year. Time to first metastasis to the skin and lymph nodes was almost identical. The vast majority of the recurrences were diagnosed at sites that were easily recognised by the patient and relatives; self-examination may therefore be a worthwhile approach. Our findings further indicate that the follow-up programme should focus on the first three years after diagnosis. PMID- 27550807 TI - Novel White Blood Cell Subtypes and Ratios in Patients With Essential Hypertension. PMID- 27550808 TI - Microglia-induced activation of non-canonical Wnt signaling aggravates neurodegeneration in demyelinating disorders. AB - Oligodendrocytes are myelinating cells of the central nervous system. Multiple sclerosis (MS) is a demyelinating disease characterized by both myelin loss and neuronal degeneration. However, the molecular mechanisms underlying neuronal degeneration in demyelinating disorders are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) demyelinating mouse model of MS, inflammatory microglia produce cytokines including interleukin-1beta (IL-1beta). Since microglia and non-canonical Wnt signaling components in neurons, such as the co-receptor Ror2, were observed in the spinal cord of EAE mice, we postulated that the interplay between activated microglia and spinal neurons under EAE conditions is mediated through non-canonical Wnt signaling. EAE treatment up regulated in vivo expression of non-canonical Wnt signaling components in spinal neurons through microglial activation. In accordance with the neuronal degeneration detected in the EAE spinal cord in vivo, co-culture of spinal neurons with microglia or the application of recombinant IL-1beta up-regulated non-canonical Wnt signaling, and induced neuronal cell death, which was suppressed by the inhibition of the Wnt-Ror2 pathway. Ectopic non-canonical Wnt signaling aggravated the demyelinating pathology in another MS mouse model due to Wnt5a-induced neurodegeneration. The linkage between activated microglia and neuronal Wnt-Ror2 signaling may provide a possible candidate target for therapeutic approaches to demyelinating disorders. PMID- 27550809 TI - The ribosome-associated Mba1 escorts Cox2 from insertion machinery to maturing assembly intermediates. AB - The three conserved core subunits of the cytochrome c oxidase are mitochondrial encoded in close to all eukaryotes. The Cox2 subunit spans the inner membrane twice, exposing N- and C-terminus into the intermembrane space. For this the N terminus is exported cotranslationally by Oxa1 and subsequently undergoes proteolytic maturation in Saccharomyces cerevisiae Little is known about the translocation of the C-terminus but Cox18 has been identified as a critical protein in this process. Here we find that the scaffold protein Cox20, which promotes processing of Cox2, is in complex with the ribosome-receptor Mba1 and translating mitochondrial ribosomes in a Cox2-dependent manner. The Mba1-Cox20 complex accumulates when export of the C-terminus of Cox2 is blocked by loss of the Cox18 protein. While Cox20 engages with Cox18, Mba1 is no longer present at this stage. Our analyses indicate that Cox20 associates with nascent Cox2 and Mba1 to promote Cox2 maturation cotranslationally. We suggest that Mba1 stabilizes the Cox20-ribosome complex and supports handover of Cox2 to the Cox18 tail export machinery. PMID- 27550810 TI - DEAD Box 1 Facilitates Removal of RNA and Homologous Recombination at DNA Double Strand Breaks. AB - Although RNA and RNA-binding proteins have been linked to double-strand breaks (DSBs), little is known regarding their roles in the cellular response to DSBs and, if any, in the repair process. Here, we provide direct evidence for the presence of RNA-DNA hybrids at DSBs and suggest that binding of RNA to DNA at DSBs may impact repair efficiency. Our data indicate that the RNA-unwinding protein DEAD box 1 (DDX1) is required for efficient DSB repair and cell survival after ionizing radiation (IR), with depletion of DDX1 resulting in reduced DSB repair by homologous recombination (HR). While DDX1 is not essential for end resection, a key step in homology-directed DSB repair, DDX1 is required for maintenance of the single-stranded DNA once generated by end resection. We show that transcription deregulation has a significant effect on DSB repair by HR in DDX1-depleted cells and that RNA-DNA duplexes are elevated at DSBs in DDX1 depleted cells. Based on our combined data, we propose a role for DDX1 in resolving RNA-DNA structures that accumulate at DSBs located at sites of active transcription. Our findings point to a previously uncharacterized requirement for clearing RNA at DSBs for efficient repair by HR. PMID- 27550812 TI - Non-transcriptional Function of FOXO1/DAF-16 Contributes to Translesion DNA Synthesis. AB - Forkhead box O (FOXO; DAF-16 in nematode) transcription factors activate a program of genes that control stress resistance, metabolism, and lifespan. Given the adverse impact of the stochastic DNA damage on organismal development and ageing, we examined the role of FOXO/DAF-16 in UV-induced DNA-damage response. Knockdown of FOXO1, but not FOXO3a, increases sensitivity to UV irradiation when exposed during S phase, suggesting a contribution of FOXO1 to translesion DNA synthesis (TLS), a replicative bypass of UV-induced DNA lesions. Actually, FOXO1 depletion results in a sustained activation of the ATR-Chk1 signaling and a reduction of PCNA monoubiquitination following UV irradiation. FOXO1 does not alter the expression of TLS-related genes but binds to the protein replication protein A (RPA1) that coats single-stranded DNA and acts as a scaffold for TLS. In Caenorhabditis elegans, daf-16 null mutants show UV-induced retardation in larval development and are rescued by overexpressing DAF-16 mutant lacking transactivation domain, but not substitution mutant unable to interact with RPA 1. Thus, our findings demonstrate that FOXO1/DAF-16 is a functional component in TLS independently of its transactivation activity. PMID- 27550811 TI - Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome. AB - Recognition of histone marks by reader modules is thought to be at the heart of epigenetic mechanisms. These protein domains are considered to function by targeting regulators to chromosomal loci carrying specific histone modifications. This is important for proper gene regulation as well as propagation of epigenetic information. The NuA4 acetyltransferase complex contains two of these reader modules, an H3K4me3-specific plant homeodomain (PHD) within the Yng2 subunit and an H3K36me2/3-specific chromodomain in the Eaf3 subunit. While each domain showed a close functional interaction with the respective histone mark that it recognizes, at the biochemical level, genetic level (as assessed with epistatic miniarray profile screens), and phenotypic level, cells with the combined loss of both readers showed greatly enhanced phenotypes. Chromatin immunoprecipitation coupled with next-generation sequencing experiments demonstrated that the Yng2 PHD specifically directs H4 acetylation near the transcription start site of highly expressed genes, while Eaf3 is important downstream on the body of the genes. Strikingly, the recruitment of the NuA4 complex to these loci was not significantly affected. Furthermore, RNA polymerase II occupancy was decreased only under conditions where both PHD and chromodomains were lost, generally in the second half of the gene coding regions. Altogether, these results argue that methylated histone reader modules in NuA4 are not responsible for its recruitment to the promoter or coding regions but, rather, are required to orient its acetyltransferase catalytic site to the methylated histone 3-bearing nucleosomes in the surrounding chromatin, cooperating to allow proper transition from transcription initiation to elongation. PMID- 27550814 TI - Role of Src family kinases in regulation of intestinal epithelial homeostasis. AB - Proper regulation of epithelial cell turnover is important for the structural integrity and homeostasis of various tissues including the intestine. Here we show that ablation of Csk, a negative regulator of Src family kinases (SFKs), specifically in intestinal epithelial cells (IECs) resulted in the development of hyperplasia throughout the intestinal epithelium of mice. Such conditional ablation of Csk also increased the proliferative activity and turnover of IECs, disturbed the differentiation of Paneth and goblet cells, reduced the number of intestinal stem cells, and attenuated the expression of Wnt target genes in the intestine. Moreover, the tyrosine phosphorylation of focal adhesion kinase (FAK) as well as the activity of both Rac and Yes-associated protein (YAP) were increased in intestinal crypts or organoids of the mutant mice, whereas inhibition of Rac or YAP activity rescued the mutant phenotypes. Our results thus suggest that SFKs promote the proliferation of IECs in intestinal crypts through activation of Rac or YAP, and that they thereby contribute to the proper regulation of IEC turnover and intestinal homeostasis. PMID- 27550816 TI - Oncogenes: piRNA flies in. PMID- 27550813 TI - Suppression of MicroRNA 200 Family Expression by Oncogenic KRAS Activation Promotes Cell Survival and Epithelial-Mesenchymal Transition in KRAS-Driven Cancer. AB - Oncogenic KRAS contributes to malignant transformation, antiapoptosis, and metastasis in multiple human cancers, such as lung, colon, and pancreatic cancers and melanoma. MicroRNAs (miRNAs) are endogenous 18- to 25-nucleotide noncoding small RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or inhibition of protein translation. In the present study, using array-based miRNA profiling in IMR90 and MCF10A cells expressing oncogenic KRAS, we identified that the expression of the microRNA 200 (mir-200) family was suppressed by KRAS activation and that this suppression was mediated by the transcription factors JUN and SP1 in addition to ZEB1. Restoration of mir 200 expression compromised KRAS-induced cellular transformation in vitro and tumor formation in vivo In addition, we found that enforced expression of mir-200 abrogated KRAS-induced resistance to apoptosis by directly targeting the antiapoptotic gene BCL2 Finally, mir-200 was able to antagonize the epithelial mesenchymal transition (EMT) driven by mutant KRAS. Collectively, our results suggest that repression of endogenous mir-200 expression is one of the important cellular responses to KRAS activation during tumor initiation and progression. PMID- 27550815 TI - Ethics in Numbers: Auditing Cleft Treatment in Mexico and Beyond. AB - Plastic surgeons around the globe are implementing projects that mix audit with medical research to ensure and improve the level of care offered to patients with cleft lip and palate. Drawing on recent literature on "audit culture" and the global growth of "performance indicators" as a form of governance, I demonstrate the conjugation of ethics and the production of numerical indicators in cleft treatment. By standardizing documentation, cleft treatment audit programs facilitate evidence-based medicine and a form of reflexive self-governance. However, the abstraction that accompanies standardization is amplified as corollary data practices travel. In emerging as the answer to improving treatment, these projects lock out the politico-economic factors that mediate medical care in resource poor settings. This danger is compounded by the tendency of numerical governance to replace political conversation with technocratic expertise. PMID- 27550817 TI - Metastasis: RIP endothelial cells. PMID- 27550818 TI - Leukaemia: Common driver gets new oncogenic mechanism. PMID- 27550822 TI - Multi-arm group sequential designs with a simultaneous stopping rule. AB - Multi-arm group sequential clinical trials are efficient designs to compare multiple treatments to a control. They allow one to test for treatment effects already in interim analyses and can have a lower average sample number than fixed sample designs. Their operating characteristics depend on the stopping rule: We consider simultaneous stopping, where the whole trial is stopped as soon as for any of the arms the null hypothesis of no treatment effect can be rejected, and separate stopping, where only recruitment to arms for which a significant treatment effect could be demonstrated is stopped, but the other arms are continued. For both stopping rules, the family-wise error rate can be controlled by the closed testing procedure applied to group sequential tests of intersection and elementary hypotheses. The group sequential boundaries for the separate stopping rule also control the family-wise error rate if the simultaneous stopping rule is applied. However, we show that for the simultaneous stopping rule, one can apply improved, less conservative stopping boundaries for local tests of elementary hypotheses. We derive corresponding improved Pocock and O'Brien type boundaries as well as optimized boundaries to maximize the power or average sample number and investigate the operating characteristics and small sample properties of the resulting designs. To control the power to reject at least one null hypothesis, the simultaneous stopping rule requires a lower average sample number than the separate stopping rule. This comes at the cost of a lower power to reject all null hypotheses. Some of this loss in power can be regained by applying the improved stopping boundaries for the simultaneous stopping rule. The procedures are illustrated with clinical trials in systemic sclerosis and narcolepsy. (c) 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID- 27550821 TI - COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy. AB - Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID- 27550819 TI - Engineered T cells: the promise and challenges of cancer immunotherapy. AB - The immune system evolved to distinguish non-self from self to protect the organism. As cancer is derived from our own cells, immune responses to dysregulated cell growth present a unique challenge. This is compounded by mechanisms of immune evasion and immunosuppression that develop in the tumour microenvironment. The modern genetic toolbox enables the adoptive transfer of engineered T cells to create enhanced anticancer immune functions where natural cancer-specific immune responses have failed. Genetically engineered T cells, so called 'living drugs', represent a new paradigm in anticancer therapy. Recent clinical trials using T cells engineered to express chimeric antigen receptors (CARs) or engineered T cell receptors (TCRs) have produced stunning results in patients with relapsed or refractory haematological malignancies. In this Review we describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail. PMID- 27550823 TI - Long non-coding RNAs in cancer metabolism. AB - Altered cellular metabolism is an emerging hallmark of cancer. Accumulating recent evidence links long non-coding RNAs (lncRNAs), a still poorly understood class of non-coding RNAs, to cancer metabolism. Here we review the emerging findings on the functions of lncRNAs in cancer metabolism, with particular emphasis on how lncRNAs regulate glucose and glutamine metabolism in cancer cells, discuss how lncRNAs regulate various aspects of cancer metabolism through their cross-talk with other macromolecules, explore the mechanistic conceptual framework of lncRNAs in reprogramming metabolism in cancers, and highlight the challenges in this field. A more in-depth understanding of lncRNAs in cancer metabolism may enable the development of novel and effective therapeutic strategies targeting cancer metabolism. PMID- 27550824 TI - Ice compresses aid the reduction of swelling and pain after scleral buckling surgery. AB - AIMS AND OBJECTIVES: To investigate the therapeutic effects of a local ice compress in alleviating eyelid swelling and errhysis and providing relief from pain after surgery. BACKGROUND: Eyelid swelling and pain are the most common postoperative symptoms after scleral buckling surgery. A local ice compress can reduce the severity of swelling, errhysis and pain after acute injury as well as after surgery. DESIGN: A retrospective study. METHODS: A total of 100 patients who had undergone scleral buckling surgery for retinal detachment were classified into an ice compress group or a control group. All patients received standard postoperative medical care: a 1% Tropicamide ophthalmic solution (Minims(r) Tropicamide; Bausch & Lomb, Surrey, UK), a 1% prednisolone acetate (Pred-Forte; Allergan, Irvine, CA, USA), an ophthalmic tobramycin 0.3%/dexamethasone 0.1% combination ointment (Tobradex(r) ; Alcon, Fort Worth, Texas, USA) and 0.5% Levofloxacin eye drops (Santen Pharmaceutical, Osaka, Japan), plus a homemade ice pack was placed over the operated eye of patients in the ice compress group for 30 minutes, three times a day for two consecutive postoperative days. RESULTS: The severity of swelling, pain and errhysis in the operated eyes was significantly lower in the ice compress group. CONCLUSIONS: The local ice compress therapy helped reduce swelling, errhysis and pain in the operated eye after scleral buckling surgery. RELEVANCE TO CLINICAL PRACTICE: Use of a local ice compress after scleral buckling surgery can reduce swelling and pain on operated eyes, providing greater comfort for patients. PMID- 27550820 TI - The biology and function of fibroblasts in cancer. AB - Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context dependent influence on cancer. PMID- 27550825 TI - Interactive effects of temperature and pCO2 on sponges: from the cradle to the grave. AB - As atmospheric CO2 concentrations rise, associated ocean warming (OW) and ocean acidification (OA) are predicted to cause declines in reef-building corals globally, shifting reefs from coral-dominated systems to those dominated by less sensitive species. Sponges are important structural and functional components of coral reef ecosystems, but despite increasing field-based evidence that sponges may be 'winners' in response to environmental degradation, our understanding of how they respond to the combined effects of OW and OA is limited. To determine the tolerance of adult sponges to climate change, four abundant Great Barrier Reef species were experimentally exposed to OW and OA levels predicted for 2100, under two CO2 Representative Concentration Pathways (RCPs). The impact of OW and OA on early life-history stages was also assessed for one of these species to provide a more holistic view of species impacts. All species were generally unaffected by conditions predicted under RCP6.0, although environmental conditions projected under RCP8.5 caused significant adverse effects: with elevated temperature decreasing the survival of all species, increasing levels of tissue necrosis and bleaching, elevating respiration rates and decreasing photosynthetic rates. OA alone had little adverse effect, even under RCP8.5 concentrations. Importantly, the interactive effect of OW and OA varied between species with different nutritional modes, with elevated pCO2 exacerbating temperature stress in heterotrophic species but mitigating temperature stress in phototrophic species. This antagonistic interaction was reflected by reduced mortality, necrosis and bleaching of phototrophic species in the highest OW/OA treatment. Survival and settlement success of Carteriospongia foliascens larvae were unaffected by experimental treatments, and juvenile sponges exhibited greater tolerance to OW than their adult counterparts. With elevated pCO2 providing phototrophic species with protection from elevated temperature, across different life stages, climate change may ultimately drive a shift in the composition of sponge assemblages towards a dominance of phototrophic species. PMID- 27550826 TI - Identification of a capsular variant and characterization of capsular acetylation in Klebsiella pneumoniae PLA-associated type K57. AB - Klebsiella pneumoniae can cause community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) is important for its virulence. Among 79 capsular (K) types discovered thus far, K57 is often associated with PLA. Here, we report the identification of a K57 variant. Cps gene locus sequencing revealed differences between the K57 reference strain 4425/51 (Ref-K57) and a variant, the PLA isolate A1142. While Ref-K57 cps contained orf13 encoding a putative acetyltransferase, the insertion of a putative transposase-encoding gene at this position was detected in A1142. This variation was detected in other K57 clinical strains. Biochemical analyses indicated that A1142 was deficient in CPS acetylation. Genetic replacement and complementation verified that orf13 was responsible for CPS acetylation. Acetylation increased CPS immunoreactivity to antiserum and enhanced K. pneumoniae induction of pro-inflammatory cytokines through JNK and MAPK signaling. While acetylation diminished the serum resistance of bacteria, it promoted adhesion to intestinal epithelial cells possibly via increasing production of type I fimbriae. In conclusion, acetylation-mediated capsular variation in K57 was observed. Capsular acetylation contributed to the variety and antigenic diversity of CPS, influenced its biological activities, and was involved in K. pneumoniae-host interactions. These findings have implications for vaccine design and pathogenicity of K. pneumoniae. PMID- 27550827 TI - Photonic microstructures for energy-generating clear glass and net-zero energy buildings. AB - Transparent energy-harvesting windows are emerging as practical building integrated photovoltaics (BIPV), capable of generating electricity while simultaneously reducing heating and cooling demands. By incorporating spectrally selective diffraction gratings as light deflecting structures of high visible transparency into lamination interlayers and using improved spectrally-selective thin-film coatings, most of the visible solar radiation can be transmitted through the glass windows with minimum attenuation. At the same time, the ultraviolet (UV) and a part of incident solar infrared (IR) radiation energy are converted and/or deflected geometrically towards the panel edge for collection by CuInSe2 solar cells. Experimental results show power conversion efficiencies in excess of 3.04% in 10 cm * 10 cm vertically-placed clear glass panels facing direct sunlight, and up to 2.08% in 50 cm * 50 cm installation-ready framed window systems. These results confirm the emergence of a new class of solar window system ready for industrial application. PMID- 27550829 TI - 'Changing colors' of third ventricular tumor in a young woman. PMID- 27550828 TI - Enriching preschool classrooms and home visits with evidence-based programming: sustained benefits for low-income children. AB - BACKGROUND: Growing up in poverty undermines healthy development, producing disparities in the cognitive and social-emotional skills that support early learning and mental health. Preschool and home-visiting interventions for low income children have the potential to build early cognitive and social-emotional skills, reducing the disparities in school readiness that perpetuate the cycle of poverty. However, longitudinal research suggests that the gains low-income children make during preschool interventions often fade at school entry and disappear by early elementary school. METHODS: In an effort to improve the benefits for low-income children, the REDI program enriched Head Start preschool classrooms (study one) and home visits (study two) with evidence-based programming, documenting positive intervention effects in two randomized trials. In this study, REDI participants were followed longitudinally, to evaluate the sustained impact of the classroom and home-visiting enrichments 3 years later, when children were in second grade. The combined sample included 556 children (55% European American, 25% African American, 19% Latino; 49% male): 288 children received the classroom intervention, 105 children received the classroom intervention plus the home-visiting intervention, and 173 children received usual practice Head Start. RESULTS: The classroom intervention led to sustained benefits in social-emotional skills, improving second grade classroom participation, student-teacher relationships, social competence, and peer relations. The coordinated home-visiting intervention produced additional benefits in child mental health (perceived social competence and peer relations) and cognitive skills (reading skills, academic performance). Significant effects ranged from 25% to 48% of a standard deviation, representing important effects of small to moderate magnitude relative to usual practice Head Start. CONCLUSIONS: Preschool classroom and home-visiting programs for low-income children can be improved with the use of evidence-based programming, reducing disparities and promoting complementary benefits that sustain in elementary school. PMID- 27550830 TI - Ternary Pd-Ni-P hybrid electrocatalysts derived from Pd-Ni core-shell nanoparticles with enhanced formic acid oxidation activity. AB - Ternary Pd-Ni-P hybrid electrocatalysts were synthesized through low temperature phosphidation of Pd-Ni core-shell nanoparticles. They show enhanced formic acid electro-oxidation activity compared to Pd, Pd-Ni and Pd-P nanoparticles, which is ascribed to the synergistic effect of the Ni and P components with Pd. PMID- 27550831 TI - Choosing between bad, worse and worst: what is the preferred mode of delivery for failure of the second stage of labor? AB - OBJECTIVE: To determine the preferred mode of delivery (vacuum, forceps or cesarean delivery) for second-stage dystocia. METHODS: Retrospective cohort study of women delivered by forceps, vacuum or cesarean delivery due to abnormalities of the second stage of labor. Primary outcome included neonatal and maternal composite adverse effects. RESULTS: A total of 547 women were included: 150 (27.4%) had forceps delivery, 200 (36.5%) had vacuum extraction, and 197 (36.1%) had cesarean section. The rate of neonatal composite outcome was significantly increased in vacuum extraction (27%) compared to forceps delivery (14.7%) or cesarean section (9.7%) (p < 0.001). There was no difference in the rate of maternal composite outcome among the groups. Both operative vaginal delivery modes were associated with significantly lower rate of postpartum infection compared to cesarean delivery (0% versus 3%, p = 0.004). CONCLUSION: Operative vaginal delivery was associated with reduced postpartum infection compared to cesarean section. Forceps delivery was associated with reduced risk for adverse neonatal outcome compared to vacuum extraction, with no increase in the risk of composite maternal complications. PMID- 27550832 TI - Genomewide analysis of bull sperm quality and fertility traits. AB - Because the priority of AI industry is to identify subfertile bulls, a predictive model that allowed for the prediction of 91% bulls of low fertility was implemented based on seminological (motility) parameters and DNA status assessed both as DNA fragmentation index (DFI) and by TUNEL assay using sperm of 105 Holstein-Friesian bulls (four batches per bull) selected based on in vivo estimated relative conception rates (ERCR). Thereafter, sperm quality and male fertility traits of bulls were explored by GWAS using a high-density (777K) Illumina chip. After data editing, 85 bulls and 591,988 SNPs were retained for GWAS. Of 12 SNPs with false discovery rate <0.2, four SNPs located on BTA28 and BTA18 were significantly associated (LD-adjusted Bonferroni <0.05) with the non compensatory sperm parameters DFI and TUNEL. Other SNPs of interest for potential association with TUNEL were found on BTA3, in the same chromosome where associations with non-compensatory in vivo bull fertility were already reported. Further suggestive SNPs for sperm membrane integrity were located on BTA28, the chromosome where QTL studies previously reported associations with sperm quality traits. Suggestive SNPs for ERCR were found on BTA18 in the vicinity of a site already associated with in vivo bull fertility. Additional SNPs associated with ERCR and sperm kinetic parameters were also identified. In contrast to other, but very few GWAS on fertility traits in bovine spermatozoa, which reported significant SNPs located on BTX, we have not identified SNPs of interest in this sexual chromosome. PMID- 27550833 TI - A microporous Cu-MOF with optimized open metal sites and pore spaces for high gas storage and active chemical fixation of CO2. AB - A microporous Cu-MOF with optimized open metal sites and pore space was constructed based on a designed bent ligand; it exhibits high-capacity multiple gas storage under atmospheric pressure and efficient catalytic activity for chemical fixation of CO2 under mild conditions. PMID- 27550834 TI - Compatibility of Radiofrequency Surgical Sponge Detection Technology with Cardiac Implantable Electronic Devices and Temporary Pacemakers. AB - BACKGROUND: Radiofrequency (RF) technology has improved detection of retained surgical sponges with a reported 100% sensitivity and specificity. However, the potential for interactions of the RF signals emitted by the detection system with cardiac implantable electronic devices (CIEDs) or temporary pacemakers may limit its use in those patients with these devices. This study investigated whether RF detection technology causes interference or clinically significant changes in the programmed settings of implanted pacemakers and defibrillators or temporary epicardial pacemakers. METHODS: Fifty patients who were scheduled either for CIED removal or placement of a temporary epicardial pacemaker (at the time of open heart surgery) were recruited for this study. Device settings and measurements from separate interrogations before and after scanning with the RF detection system were compared. For the temporary pacemakers, we observed for any changes in hemodynamics or signs of pacing interference. RESULTS: Twenty (40%) pacemakers, 20 (40%) implantable cardioverter defibrillators, and 10 (20%) temporary pacemakers were analyzed in this study. During scanning, no signal interference was detected in any permanent device, and there were no significant changes in programmed settings after scanning with the RF detection system. However, pacing inhibition was detected with temporary pacing systems when programmed to a synchronous mode (DDD). CONCLUSIONS: RF detection technology can be safely used to scan for retained surgical sponges in patients with permanent CIEDs and temporary pacemakers set to asynchronous mode. PMID- 27550835 TI - Manipulation of ubiquitin/SUMO pathways in human herpesviruses infection. AB - Post-translational modification of proteins with ubiquitin/small ubiquitin-like modifier (SUMO) molecules triggers multiple signaling pathways that are critical for many aspects of cellular physiology. Given that viruses hijack the biosynthetic and degradative systems of their host, it is not surprising that viruses encode proteins to manipulate the host's cellular machinery for ubiquitin/SUMO modification at multiple levels. Infection with a herpesvirus, among the most ubiquitous human DNA viruses, has been linked to many human diseases, including cancers. The interplay between human herpesviruses and the ubiquitylation/SUMOylation modification system has been extensively investigated in the past decade. In this review, we present an overview of recent advances to address how the ubiquitin/SUMO-modified system alters the latency and lytic replication of herpesvirus and how herpesviruses usurp the ubiquitin/SUMO pathways against the host's intrinsic and innate immune response to favor their pathogenesis. PMID- 27550836 TI - Data quality issues in proteomics - there are many paths to enlightenment. PMID- 27550837 TI - MiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemia. AB - Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1 positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis. In vivo, miR-146b overexpression in a TAL1 positive cell line extends mouse survival in a xenotransplant model of human T ALL. In contrast, knockdown of miR-146b-5p results in leukemia acceleration and decreased mouse overall survival, paralleled by faster tumor infiltration of the central nervous system. Our results suggest that miR-146b-5p is a functionally relevant microRNA gene in the context of T-ALL, whose negative regulation by TAL1 and possibly other oncogenes contributes to disease progression by modulating leukemia cell motility and disease aggressiveness. PMID- 27550839 TI - Resolution of inverse psoriasis after treatment with levodopa for Parkinson's disease. AB - Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous areas of the body. It has a prevalence of 2% worldwide. The usefulness of levodopa in psoriasis was discovered in 1970 but nowadays it is not a standard therapy for this condition. A 74-year-old woman was diagnosed with Parkinson's disease subsequent to the development of extensive inverse psoriasis. The skin lesions were resistant to classical topical and systemic medications. Treatment with levodopa was initiated in order to treat her neurological problem and progressive remission of the skin lesions was noted. We highlight the role of dopamine in the pathophysiology of this dermatosis. PMID- 27550838 TI - Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis. AB - BACKGROUND: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven. OBJECTIVES: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA). SEARCH STRATEGY: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour. SELECTION CRITERIA: We selected trials including pregnant women between 24 and 36(6/7) weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment. DATA COLLECTION AND ANALYSIS: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed. MAIN RESULTS: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) >= grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01). CONCLUSION: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice. TWEETABLE ABSTRACT: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation. PMID- 27550841 TI - What we're trying to solve: the back and forth of engaged interdisciplinary inquiry. AB - Interdisciplinary research assumes that teams of highly specialized scientists develop new knowledge by bridging their respective horizons. Nurse educators preparing nursing doctoral students to conduct interdisciplinary research need insight into how members of interdisciplinary research teams experience knowledge horizons in these complex contexts. Based on the work of the philosopher Bernard Lonergan, this pilot study uses Transcendental Method for Research with Human Subjects to explore interdisciplinary researchers' experiences with and attitudes toward interdisciplinary research. Results reveal the overarching conceptual category of "engaged interdisciplinary inquiry" which includes six themes: (i) valuing interdisciplinary engagement; (ii) direct engagement; (iii) interior engagement; (iv) disengagement; (v) facilitated engagement and (vi) engaged researcher development. Results also suggest engagement depends on vigorous "back and forth", or dialogue, with self and others, and demonstrate the study method is fruitful for cognitive inquiry. This pilot supports expanded study to inform preparation for and conduct of interdisciplinary research involving nurses and raises important questions about how the trend toward interdisciplinary research affects nursing science. PMID- 27550840 TI - Role of vocal tract characteristics in individual discrimination by Japanese macaques (Macaca fuscata). AB - The Japanese macaque (Macaca fuscata) exhibits a species-specific communication sound called the "coo call" to locate group members and maintain within-group contact. Monkeys have been demonstrated to be capable of discriminating between individuals based only on their voices, but there is still debate regarding how the fundamental frequencies (F0) and filter properties of the vocal tract characteristics (VTC) contribute to individual discrimination in nonhuman primates. This study was performed to investigate the acoustic keys used by Japanese macaques in individual discrimination. Two animals were trained with standard Go/NoGo operant conditioning to distinguish the coo calls of two unfamiliar monkeys. The subjects were required to continue depressing a lever until the stimulus changed from one monkey to the other. The test stimuli were synthesized by combining the F0s and VTC from each individual. Both subjects released the lever when the VTC changed, whereas they did not when the F0 changed. The reaction times to the test stimuli were not significantly different from that to the training stimuli that shared the same VTC. Our data suggest that vocal tract characteristics are important for the identification of individuals by Japanese macaques. PMID- 27550843 TI - Dysregulation of the glutamatergic receptors after antidepressant treatment in human neural progenitor cells. PMID- 27550842 TI - CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery. AB - The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery. PMID- 27550845 TI - Setting the System Boundaries of "Energy for Water" for Integrated Modeling. PMID- 27550846 TI - Orf virus interleukin-10 and vascular endothelial growth factor-E modulate gene expression in cultured equine dermal fibroblasts. AB - BACKGROUND: Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals. HYPOTHESIS/OBJECTIVES: The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression and behaviour in a manner conducive to healing. ANIMALS: Skin samples were harvested from the lateral thoracic wall of two healthy thoroughbred horses. METHODS: Equine dermal cells were isolated using a skin explant method and their phenotype assessed by immunofluorescence. Cells were treated with recombinant proteins, with or without inflammatory stimuli. Gene expression was examined using standard and quantitative reverse transcriptase PCR. Cell behaviour was evaluated in a scratch assay. RESULTS: Cultured cells were half vimentin(+ve) fibroblasts and half alpha smooth muscle actin(+ve) and vimentin(+ve) myofibroblasts. VEGF-E increased basal expression of IL-10 mRNA, whereas VEGF-A and collagenase-1 mRNA expression was increased by ovIL-10. In cells exposed to inflammatory stimulus, both treatments dampened tumour necrosis factor mRNA expression, and ovIL-10 exacerbated expression of monocyte chemoattractant protein. Neither viral protein influenced cell migration greatly. CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows that VEGF-E and ovIL-10 are active on equine dermal cells and exert anti inflammatory and anti-fibrotic effects that may enhance skin wound healing in horses. PMID- 27550844 TI - De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females. AB - Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family. PMID- 27550847 TI - Prevalence of Delirium in Older Medical Inpatients in Tanzania. PMID- 27550848 TI - Murine tribbles homolog 2 deficiency affects erythroid progenitor development and confers macrocytic anemia on mice. AB - Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the physiological function of Trib2 in hematopoietic system remains to be elucidated. Here, we report that Trib2 knockout (KO) mice manifest macrocytic anemia and increase of T lymphocytes. Although Trib2 deficient RBCs have similar half-life as the control RBCs, Trib2 KO mice are highly vulnerable to oxidant induced hemolysis. Endogenous Trib2 mRNA is expressed in early hematopoietic progenitors, erythroid precursors, and lymphoid lineages, but not in mature RBCs, myeloid progenitors and granulocytes. Consistently, flow cytometric analysis and in vitro colony forming assay revealed that deletion of Trib2 mainly affected erythroid lineage development, and had no effect on either granulocyte or megakaryocyte lineages in bone marrow. Furthermore, a genetic approach using double knockout of Trib2 and C/ebpalpha genes in mice suggested that Trib2 promotes erythropoiesis independent of C/ebpalpha proteins in vivo. Finally, ectopic expression of human Trib2 in zebrafish embryos resulted in increased expression of erythropoiesis-related genes and of hemoglobin. Taking all data together, our results suggest that Trib2 positively promotes early erythrocyte differentiation and is essential for tolerance to hemolysis. PMID- 27550849 TI - Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? AB - The incidence of differentiated thyroid cancer is increasing greatly in high income countries. Roughly 50% of this increase is attributable to the identification of intrathyroidal papillary thyroid microcarcinomas. Since mortality associated with these tumours remains low and stable, the increasing diagnosis has led to concerns about overdiagnosis and overtreatment. Management of papillary thyroid microcarcinomas should take into account the reported absence of mortality when diagnosed in the absence of lymph node metastases and distant metastases, as shown even in recent studies promoting active surveillance; a low recurrence rate of 1-5%; and the risk of permanent complications from surgery that cannot be decreased to less than 1-3%, even in high-volume tertiary care centres with experienced surgeons. On the basis of these data, active surveillance with curative intent, in which active treatment is delayed until the cancer shows signs of significant progression to avoid side effects of treatment, should be considered in properly selected patients. PMID- 27550851 TI - Haematological cancer: Carfilzomib is superior to bortezomib in rMM. PMID- 27550850 TI - Vitamin D Deficiency in Pediatric Fracture Patients: Prevalence, Risk Factors, and Vitamin D Supplementation. AB - OBJECTIVE: Although vitamin D levels are not routinely monitored in pediatric fracture patients, identification of children with a vitamin D deficiency may be clinically relevant because of the potential role of vitamin D in fracture healing. This study aimed to determine the prevalence of vitamin D deficiency in a pediatric fracture population and to identify risk factors for deficiency. METHODS: All pediatric patients (<18 years) who were treated for a fracture of the upper or lower extremity from September 2012 to October 2013 in the outpatient setting of a level one trauma center were included in this cross sectional study. Vitamin D deficiency was defined as a serum calcidiol <50 nmol/L. Potential risk factors for vitamin D deficiency were analysed using multivariable logistic regression analysis. RESULTS: A total of 108 boys (58%) and 79 girls, of a mean age 11.1 years (standard deviation 3.9), who had undergone 189 fractures were included in the study. Sixty-four children (34%) were vitamin D deficient. Of those with follow-up measurements, 74% were no longer deficient after supplementation. Vitamin D status did not influence the occurrence of complications during fracture treatment. Independent risk factors for vitamin D deficiency were older age, season (spring), and a non-Caucasian skin type. CONCLUSION: Clinicians who treat children with a fracture should inform patients and parents on vitamin D supplementation. Vitamin D measurement and supplementation may be needed for children with a non-Caucasian skin type or for those who present with a fracture during spring months. PMID- 27550852 TI - Correction regarding data on blinatumomab-associated seizures. PMID- 27550853 TI - Pancreatic cancer: Promise of doublet chemotherapy. PMID- 27550854 TI - Genetics: Surveillance effective for TP53-mutation carriers. PMID- 27550855 TI - Correction regarding data on blinatumomab-associated seizures. PMID- 27550856 TI - Sarcoma: Genetic determinants of sarcoma risk revealed. PMID- 27550858 TI - Somatic AKT1 mutations cause meningiomas colocalizing with a characteristic pattern of cranial hyperostosis. AB - Somatic genetic mutations in meningiomas are associated with histologic subtypes, anatomical location, and grade. Concomitant hyperostosis occurs with some meningiomas and the pathogenesis is not well understood. Cranial hyperostosis and meningiomas are common in patients with Proteus syndrome, which is caused by a somatic activating mutation in AKT1 c.49G>A. This same mutation has also been found in 6-9% of sporadic non-syndromic meningiomas. Sixty-one patients with Proteus syndrome meeting clinical diagnostic criteria were evaluated at the NIH from 1997 to 2014. Of these 61, 52 had a somatic activating mutation (c.49G>A, p.Glu17Lys) in AKT1 confirmed from affected tissue samples. Photographs, physical examination and/or autopsy, X-rays, CT, and/or MRI scan of the head were reviewed in 29/52 patients. Of the 29 patients, the most common intracranial tumor was meningioma, all co-localizing with cranial hyperostosis, and diagnosed at younger ages than typical for isolated, non-syndromic meningiomas. These patients had progressive cranial overgrowth that consisted primarily of diploic space expansion, and was characterized by unilateral, parasagittal, and frontal bone involvement. We hypothesize that sporadic meningothelial and transitional subtype meningiomas are a forme fruste or microform of Proteus syndrome, and activation of the AKT/PI3K pathway drives hyperostosis in both non-syndromic, and Proteus related meningiomas. (c) 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID- 27550857 TI - Does the mobilization of circulating tumour cells during cancer therapy cause metastasis? AB - Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumours, distant metastasis remains a very common - and usually fatal - mode of failure after attempted curative treatment. Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. Distant metastasis occurring after treatment can arise from previously undetected micrometastases or, alternatively, from persistent locoregional disease. Another possibility is that treatment itself might sometimes cause or promote metastasis. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumour cells (CTCs). High CTC numbers are associated with an unfavourable prognosis in many cancers. Radiotherapy and systemic antitumour therapies might also mobilize CTCs. We review the preclinical and clinical data concerning cancer treatments, CTC mobilization and other factors that might promote metastasis. Contemporary treatment regimens represent the best available curative options for patients who might otherwise die from locally confined, advanced-stage cancers; however, if such treatments can promote metastasis, this process must be understood and addressed therapeutically to improve patient survival. PMID- 27550859 TI - Prosteatotic and Protective Components in a Unique Model of Fatty Liver: Gut Microbiota and Suppressed Complement System. AB - Goose can develop severe hepatic steatosis without overt injury, thus it may serve as a unique model for uncovering how steatosis-related injury is prevented. To identify the markedly prosteatotic and protective mechanisms, we performed an integrated analysis of liver transcriptomes and gut microbial metagenomes using samples collected from overfed and normally-fed geese at different time points. The results indicated that the fatty liver transcriptome, initially featuring a 'metabolism' pathway, was later joined by 'cell growth and death' and 'immune diseases' pathways. Gut microbiota played a synergistic role in the liver response as microbial and hepatic genes affected by overfeeding shared multiple pathways. Remarkably, the complement system, an inflammatory component, was comprehensively suppressed in fatty liver, which was partially due to increased blood lactic acid from enriched Lactobacillus. Data from in vitro studies suggested that lactic acid suppressed TNFalpha via the HNF1alpha/C5 pathway. In conclusion, gut microbes and their hosts respond to excess energy influx as an organic whole, severe steatosis and related tolerance of goose liver may be partially attributable to gut microbiotic products and suppressed complement system, and lactic acid from gut microbiota participates in the suppression of hepatic TNFalpha/inflammation through the HNF1alpha/C5 pathway. PMID- 27550860 TI - Harnessing Defect-Tolerance at the Nanoscale: Highly Luminescent Lead Halide Perovskite Nanocrystals in Mesoporous Silica Matrixes. AB - Colloidal lead halide perovskite nanocrystals (NCs) have recently emerged as a novel class of bright emitters with pure colors spanning the entire visible spectral range. Contrary to conventional quantum dots, such as CdSe and InP NCs, perovskite NCs feature unusual, defect-tolerant photophysics. Specifically, surface dangling bonds and intrinsic point defects such as vacancies do not form midgap states, known to trap carriers and thereby quench photoluminescence (PL). Accordingly, perovskite NCs need not be electronically surface-passivated (with, for instance, ligands and wider-gap materials) and do not noticeably suffer from photo-oxidation. Novel opportunities for their preparation therefore can be envisaged. Herein, we show that the infiltration of perovskite precursor solutions into the pores of mesoporous silica, followed by drying, leads to the template-assisted formation of perovskite NCs. The most striking outcome of this simple methodology is very bright PL with quantum efficiencies exceeding 50%. This facile strategy can be applied to a large variety of perovskite compounds, hybrid and fully inorganic, with the general formula APbX3, where A is cesium (Cs), methylammonium (MA), or formamidinium (FA), and X is Cl, Br, I or a mixture thereof. The luminescent properties of the resulting templated NCs can be tuned by both quantum size effects as well as composition. Also exhibiting intrinsic haze due to scattering within the composite, such materials may find applications as replacements for conventional phosphors in liquid-crystal television display technologies and in related luminescence down-conversion-based devices. PMID- 27550861 TI - Coarse climate change projections for species living in a fine-scaled world. AB - Accurately predicting biological impacts of climate change is necessary to guide policy. However, the resolution of climate data could be affecting the accuracy of climate change impact assessments. Here, we review the spatial and temporal resolution of climate data used in impact assessments and demonstrate that these resolutions are often too coarse relative to biologically relevant scales. We then develop a framework that partitions climate into three important components: trend, variance, and autocorrelation. We apply this framework to map different global climate regimes and identify where coarse climate data is most and least likely to reduce the accuracy of impact assessments. We show that impact assessments for many large mammals and birds use climate data with a spatial resolution similar to the biologically relevant area encompassing population dynamics. Conversely, impact assessments for many small mammals, herpetofauna, and plants use climate data with a spatial resolution that is orders of magnitude larger than the area encompassing population dynamics. Most impact assessments also use climate data with a coarse temporal resolution. We suggest that climate data with a coarse spatial resolution is likely to reduce the accuracy of impact assessments the most in climates with high spatial trend and variance (e.g., much of western North and South America) and the least in climates with low spatial trend and variance (e.g., the Great Plains of the USA). Climate data with a coarse temporal resolution is likely to reduce the accuracy of impact assessments the most in the northern half of the northern hemisphere where temporal climatic variance is high. Our framework provides one way to identify where improving the resolution of climate data will have the largest impact on the accuracy of biological predictions under climate change. PMID- 27550862 TI - Response to Re: Incidence and risk factors for acute kidney injury after radical cystectomy. PMID- 27550863 TI - Data Quality Influences Observed Links Between Functional Connectivity and Behavior. AB - A growing field of research explores links between behavioral measures and functional connectivity (FC) assessed using resting-state functional magnetic resonance imaging. Recent studies suggest that measurement of these relationships may be corrupted by head motion artifact. Using data from the Human Connectome Project (HCP), we find that a surprising number of behavioral, demographic, and physiological measures (23 of 122), including fluid intelligence, reading ability, weight, and psychiatric diagnostic scales, correlate with head motion. We demonstrate that "trait" (across-subject) and "state" (across-day, within subject) effects of motion on FC are remarkably similar in HCP data, suggesting that state effects of motion could potentially mimic trait correlates of behavior. Thus, head motion is a likely source of systematic errors (bias) in the measurement of FC:behavior relationships. Next, we show that data cleaning strategies reduce the influence of head motion and substantially alter previously reported FC:behavior relationship. Our results suggest that spurious relationships mediated by head motion may be widespread in studies linking FC to behavior. PMID- 27550864 TI - Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits. AB - Subconvulsive hippocampal neural disinhibition, that is reduced GABAergic inhibition, has been implicated in neuropsychiatric disorders characterized by attentional and memory deficits, including schizophrenia and age-related cognitive decline. Considering that neural disinhibition may disrupt both intra hippocampal processing and processing in hippocampal projection sites, we hypothesized that hippocampal disinhibition disrupts hippocampus-dependent memory performance and, based on strong hippocampo-prefrontal connectivity, also prefrontal-dependent attention. In support of this hypothesis, we report that acute hippocampal disinhibition by microinfusion of the GABA-A receptor antagonist picrotoxin in rats impaired hippocampus-dependent everyday-type rapid place learning performance on the watermaze delayed-matching-to-place test and prefrontal-dependent attentional performance on the 5-choice-serial-reaction-time test, which does not normally require the hippocampus. For comparison, we also examined psychosis-related sensorimotor effects, using startle/prepulse inhibition (PPI) and locomotor testing. Hippocampal picrotoxin moderately increased locomotion and slightly reduced startle reactivity, without affecting PPI. In vivo electrophysiological recordings in the vicinity of the infusion site showed that picrotoxin mainly enhanced burst firing of hippocampal neurons. In conclusion, hippocampal neural disinhibition disrupts hippocampus-dependent memory performance and also manifests through deficits in not normally hippocampus-dependent attentional performance. These behavioral deficits may reflect a disrupted control of burst firing, which may disrupt hippocampal processing and cause aberrant drive to hippocampal projection sites. PMID- 27550865 TI - The Deceptively Simple N170 Reflects Network Information Processing Mechanisms Involving Visual Feature Coding and Transfer Across Hemispheres. AB - A key to understanding visual cognition is to determine "where", "when", and "how" brain responses reflect the processing of the specific visual features that modulate categorization behavior-the "what". The N170 is the earliest Event Related Potential (ERP) that preferentially responds to faces. Here, we demonstrate that a paradigmatic shift is necessary to interpret the N170 as the product of an information processing network that dynamically codes and transfers face features across hemispheres, rather than as a local stimulus-driven event. Reverse-correlation methods coupled with information-theoretic analyses revealed that visibility of the eyes influences face detection behavior. The N170 initially reflects coding of the behaviorally relevant eye contralateral to the sensor, followed by a causal communication of the other eye from the other hemisphere. These findings demonstrate that the deceptively simple N170 ERP hides a complex network information processing mechanism involving initial coding and subsequent cross-hemispheric transfer of visual features. PMID- 27550867 TI - Timing of White Matter Development Determines Cognitive Abilities at School Entry but Not in Late Adolescence. AB - The primary aim of this study was to investigate to what degree the age-related white matter development, here called "brain age", is associated with working memory (WM) and numeric abilities in 6-year-old children. We measured white matter development using diffusion tensor imaging to calculate fractional anisotropy (FA). A "brain age" model was created using multivariate statistics, which described association between FA and age in a sample of 6- to 20-year-old children. This age model was then applied to predict "brain age" in a second sample of 6-year-old children. The predicted brain age correlated with WM performance and numerical ability (NA) (P < 0.01, P < 0.05) in the 6-year-old children. More than 50% of the stable variance in WM performance was explained. We found that in children older than 13 years of age, this association between brain age and WM was no longer significant (P > 0.5). The results bear theoretical implications as they suggest that the variability in individual developmental timing strongly affects WM and NA at school start but badly predicts adolescent cognitive functioning. Furthermore, it bears practical implications as one may differentiate maturation lags from persistent low cognitive abilities in school children, complementing cognitive tests. PMID- 27550866 TI - Stimulus-Driven Reorienting Impairs Executive Control of Attention: Evidence for a Common Bottleneck in Anterior Insula. AB - A classical model of human attention holds that independent neural networks realize stimulus-driven reorienting and executive control of attention. Questioning full independence, the two functions do, however, engage overlapping networks with activations in cingulo-opercular regions such as anterior insula (AI) and a reverse pattern of activation (stimulus-driven reorienting), and deactivation (executive control) in temporoparietal junction (TPJ). To test for independent versus shared neural mechanisms underlying stimulus-driven and executive control of attention, we used fMRI and a task that isolates individual from concurrent demands in both functions. Results revealed super-additive increases of left AI activity and behavioral response costs under concurrent demands, suggesting a common bottleneck for stimulus-driven reorienting and executive control of attention. These increases were mirrored by non-additive decreases of activity in the default mode network (DMN), including posterior TPJ, regions where activity increased with off-task processes. The deactivations in posterior TPJ were spatially separated from stimulus-driven reorienting related activation in anterior TPJ, a differentiation that replicated in task-free resting state. Furthermore, functional connectivity indicated inhibitory coupling between posterior TPJ and AI during concurrent attention demands. These results demonstrate a role of AI in stimulus-driven and executive control of attention that involves down-regulation of internally directed processes in DMN. PMID- 27550869 TI - Physicochemical and Microstructural Characterization of Corn Starch Edible Films Obtained by a Combination of Extrusion Technology and Casting Technique. AB - Starch edible films (EFs) have been widely studied due to their potential in food preservation; however, their application is limited because of their poor mechanical and barrier properties. Because of that, the aim of this work was to use the extrusion technology (Ex T) as a pretreatment of casting technique to change the starch structure in order to obtain EFs with improved physicochemical properties. To this, corn starch and a mixture of plasticizers (sorbitol and glycerol, in different ratios) were processed in a twin screw extruder to generate the starch modification and subsequently casting technique was used for EFs formation. The best conditions of the Ex T and plasticizers concentration were obtained using response surface methodology. All the response variables evaluated, were affected significatively by the Plasticizers Ratio (Sorbitol:Glycerol) (PR (S:G)) and Extrusion Temperature (ET), while the Screw Speed (SS) did not show significant effect on any of these variables. The optimization study showed that the appropriate conditions to obtain EFs with the best mechanical and barrier properties were ET = 89 degrees C, SS = 66 rpm and PR (S:G) = 79.7:20.3. Once the best conditions were obtained, the optimal treatment was characterized according to its microstructural properties (X-ray diffraction, Scanning Electron Microscopy and Atomic Force Microscopy) to determine the damage caused in the starch during Ex T and casting technique. In conclusion, with the combination of Ex T and casting technique were obtained EFs with greater breaking strength and deformation, as well as lower water vapor permeability than those reported in the literature. PMID- 27550868 TI - Functional Network Dynamics of the Language System. AB - During linguistic processing, a set of brain regions on the lateral surfaces of the left frontal, temporal, and parietal cortices exhibit robust responses. These areas display highly correlated activity while a subject rests or performs a naturalistic language comprehension task, suggesting that they form an integrated functional system. Evidence suggests that this system is spatially and functionally distinct from other systems that support high-level cognition in humans. Yet, how different regions within this system might be recruited dynamically during task performance is not well understood. Here we use network methods, applied to fMRI data collected from 22 human subjects performing a language comprehension task, to reveal the dynamic nature of the language system. We observe the presence of a stable core of brain regions, predominantly located in the left hemisphere, that consistently coactivate with one another. We also observe the presence of a more flexible periphery of brain regions, predominantly located in the right hemisphere, that coactivate with different regions at different times. However, the language functional ROIs in the angular gyrus and the anterior temporal lobe were notable exceptions to this trend. By highlighting the temporal dimension of language processing, these results suggest a trade-off between a region's specialization and its capacity for flexible network reconfiguration. PMID- 27550870 TI - Efficacy of bimatoprost in the treatment of non-facial vitiligo. PMID- 27550871 TI - Direct Hyperbilirubinemia in an Infant. PMID- 27550872 TI - Synthetic Cannabinoid Exposure: A New Risk for Children? PMID- 27550873 TI - Pediatric Firework-Related Injuries Presenting to United States Emergency Departments, 1990-2014. AB - This study characterizes the epidemiology of nonfatal pediatric firework-related injuries in the United States among children and adolescents by analyzing data from the National Electronic Injury Surveillance System from 1990 through 2014. During this 25-year period, an estimated 136 991 (95% CI = 113 574-160 408) children <20 years old were treated in US emergency departments for firework related injuries. The annual injury rate decreased significantly by 30.4% during this period. Most of those injured were male (75.7%), mean patient age was 10.6 years, and 7.6% required hospital admission. The hands (30.0%) were the most commonly injured body region, followed by head and neck (22.2%), and eyes (21.5%). Sixty percent of injuries were burns. Injuries were most commonly associated with firecrackers (26.2%), aerial devices (16.3%), and sparklers (14.3%). Consumer fireworks pose a serious injury risk to pediatric users and bystanders, and families should be encouraged to attend public firework displays rather than use consumer fireworks. PMID- 27550874 TI - All-optical analog comparator. AB - An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID- 27550875 TI - Impact of Frailty on Cardiovascular Disease (and the Other Way Around). AB - Cardiovascular disesase has been identified as the most frequent cause of death, while frailty has been identified as one of geriatric giants characterized by decreased physiological reserves and increased vulnerability. Despite of aggressive treatment for cardiovascular diseases such as invasive methods,frail patients who undergo these procedures tend to experience undesirable effects compared to non frail patients. As the population of elderly patiens worldwide is growing larger, these issues lead to major health problems that we have to overcome. Association between frailty and cardiovascular disease is still debatable. Cardiovascular disease accelerates frailty. On the other hand, frail patients have higher risk of cardiac mortality and major cardiac events due to their complex health status. However, by doing good risk prediction and assessment, interventional treatment can be performed safely in selected older patients. To date, only a few studies have been conducted to investigate relationship between these two major health problems in elderly. Therefore, in this edition we highlight a study which investigate association between frailty and major adverse cardiac events in patients who underwent invasive intervention. Further researches are still needed to establish evidences between these two geriatric major health problems. PMID- 27550876 TI - The Effectiveness of a Three Day Course Antibiotic Post-urodynamic Study in Preventing Lower Urinary Tract Infection. AB - AIM: to evaluate the effect of a 3-day course antibiotic post-urodynamic study (UDS) to prevent urinary tract infection (UTI). METHODS: this was a randomized double blind clinical trial on the proportion of UTI in patients who received levofloxacin 500 mg once a day for 3 days after UDS compared to nontreated patients. The outcome of this study was the incidence of lower UTI in levofloxacin group and placebo group. Lower UTI was defined as patient with one or more clinical symptoms of lower UTI and one or more urinalysis parameter of UTI. Chi-square was used to evaluate the association between the lower UTI and treatment group. RESULTS: a total of 126 patients were enrolled in this study from two outpatient urology clinics in Jakarta: Cipto Mangunkusumo Hospital and Asri Hospital. Overall, 26 patients (20.6%) had UTI post UDS (8 out of 63 patients from levofloxacin arm (12.7%) and 18 out of 63 patients from placebo arm (28.6%); p=0.028). The most common isolate found was E. coli (n=18 patients; 69.2%). The most common indications to perform UDS were Lower Urinary Tract Symptoms (LUTS) with failure of therapy (n=43 patients; 25%), LUTS after invasive treatment (n=29 patients; 16.9%), and overactive bladder with failure of therapy (n=22 patients; 12.7%). CONCLUSION: the use of antibiotic post-UDS can prevent incidence of lower UTI. PMID- 27550877 TI - Impact of Frailty on the First 30 Days of Major Cardiac Events in Elderly Patients with Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention. AB - AIM: to obtain the proportion of frailty and the incidence of 30-day major adverse cardiovascular events (MACE) as well as to review the impact of frailty on the prognosis of elderly patients with coronary heart disease who underwent elective PCI. METHODS: this is a prospective cohort study to assess the frailty of elderly patients with coronary artery disease that underwent elective PCI in Cipto Mangunkusumo Hospital using the frailty phenotype criteria. They were subsequently followed-up for 30 days to see whether there was any MACE developed. RESULTS: there were 100 elderly patients with coronary artery disease who underwent elective PCI between September 2014 and June 2015. The mean age of patients was 66.95 (SD 4.875) years and 69% of the patients were males. Frailty was present in 61% of the patients. MACE were occurred in 8.19% of frail patients and 5.12% were occurred in non-frail patients. The association between frailty and MACE was demonstrated by the result of crude HR of 1.6 (CI 95% 0.31-8.24). In our study, the 30-day survival rate was 95% in frail patients and 98% in non frail patients. CONCLUSION: there is a 1.6-fold increased risk of 30-day MACE in elderly frail patients undergoing elective PCI; however, it is not statistically significant. PMID- 27550878 TI - Early Realignment Versus Delayed Urethroplasty in Management of Pelvic Fracture Urethral Injury: A Meta-analysis. AB - AIM: this meta-analysis study will evaluate the incidence of urethral stricture as a successfull parameter in the management of PFUI through early realignment, compared with delayed urethroplasty. Long-term complications such as erectile dysfunction and incontinence on both methods will also be evaluated. METHODS: online literature was sourced from Pubmed, Embase, Cochrane, and Google Scholar. The incidence of stricture was evaluated from the entire study group of ER and DU. Stricture of the urethra is diagnosed by the symptoms such as the obstruction that felt by the patient, uroflowmetry examination, and urine residual post micturition that supported by urethrography examination at regular interval. In some cases the incidence of stricture also diagnosed by urethroscopy. The patient is assessed as not having stricture when it is no longer needed to do urethral dilatation or advanced urethrotomy. The rate of incontinence was assessed subjectively from the patient's complaints. The erectile function assessed subjectively; decreased of tumesen's degree, reduced the duration of erection, and penetration failure diagnosed as erection dysfunction. The data were processed as dichotomy data to calculate the risk ratio using Review Manager 5.1. RESULTS: five relevant literatures reviewed in this study. The incidence of urethral strictures are statistically significant lower in early realignment group (RR=0.70, 95% CI 0.50-0.99, P<0.05). There were no statistically significant differences between both treatment groups on the incidence of erectile dysfunction (RR=0.72, 95% CI 0.39-1.34) nor the incidence of incontinence (RR=0.74, 95% CI 0.36-1.51). CONCLUSION: early realignment decrease the occurrence of stricture on PFUI treatment compared to delayed urethroplasty method. Between the two methos, the complications such as erectile dysfunction and incontinence; however, there was no significant difference. PMID- 27550879 TI - Low Plasma Atherogenic Index Associated with Poor Prognosis in Hospitalized Patients with Acute Myocardial Infarction. AB - AIM: the impact of atherogenic index of plasma (AIP), calculated as logarithmic of triglyceride:HDL ratio (log10.[TG:HDL]), on major adverse cardiovascular events (MACE) during acute myocardial infarction (AMI) has not been fully accepted. This study aims to investigate the role of AIP in predicting major adverse cardiovascular events following AMI during intensive care in the hospital. METHODS: this was a prospective cohort study. We enrolled subjects with AMI hospitalized in intensive coronary care unit at Dr. Sardjito General Hospital, Yogyakarta. The AIP was measured in fasting blood within 24 hours of hospital admission. The total cholesterol, LDL, HDL, and triglyceride (TG), were measured and AIP value was determined as log10.[TG:HDL]). Based on AIP value, subjects were allocated into low AIP (<0.24) and high AIP (0.24). The outcome of the study was major adverse cardiovascular events during hospitalization, i.e. multipart of all cause mortality, acute heart failure, cardiogenic shock, reinfarction, and rescucitated VT/VF. RESULTS: among 277 subjects, the high AIP group comprised 213 subjects (77%) and low AIP group comprised 64 subjects (33%). During intensive hospitalisation, 66 subjects (24%) developed MACE and 20 subjects (7%) developed fatal outcome (all cause mortality). The incidence of MACE tended to be higher in low AIP group, however its difference was not significant. The incidence of all cause mortality was significantly higher in low AIP group (14%) than in high AIP group (5%). Multivariable analysis showed that low AIP predicted all cause mortality independently with a risk ratio 3.71 (95% CI 1.26-10.97, p=0.02). CONCLUSION: low AIP value (<0.24) is an independent predictor for all cause mortality in patients with acute myocardial infarction undergoing intensive hospitalisation. PMID- 27550880 TI - Pain Reduction After Laser Acupuncture Treatment in Geriatric Patients with Knee Osteoarthritis: a Randomized Controlled Trial. AB - AIM: to compare the effectiveness of active laser acupuncture with placebo on reducing pain intensity and improving functional outcome in geriatric patients with knee osteoarthritis (OA). METHODS: a double-blind randomized controlled trial was conducted in geriatrics with knee OA at Medical Acupuncture Outpatient Clinic, Integrated Geriatric Outpatient Clinic, Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital, Jakarta, during May to October 2015. Sixty two patients with knee OA were randomly assigned into two groups: active laser acupuncture group or placebo laser acupuncture group. Interventions were carried out using a gallium aluminum arsenide laser device at the ST35 Dubi, ST36 Zusanli, SP9 Yinlingquan, GB34 Yanglingquan and EX - LE - 4 Neixiyan acupuncture points on the affected knee for ten sessions of treatment, i.e. twice a week. Patients were assessed using a visual analogue scale (VAS) and Lequesne index at baseline, after four sessions, after nine sessions and at 2 weeks after the treatment had been stopped. RESULTS: the VAS scores were significantly improved in the active laser acupuncture group compared to the placebo group. The evaluation of VAS scores was carried out after four treatment sessions (mean difference: 0.39; p<0.001), after nine treatment sessions (mean difference: 37.48; p<0.001) and at 2 weeks post intervention (mean difference: 39.15; p<0.001). The evaluation also showed significant improvement of Lequesne index after four treatment sessions (mean difference: 4.68; p<0.001), after nine treatment sessions (mean difference: 5.90; p<0.001) and at 2 weeks post intervention (mean difference: 6.48; p<0.001). CONCLUSION: active laser acupuncture is effective in reducing pain. PMID- 27550881 TI - The Proportion of Orthostatic Hypotension and Its Relationship with HbA1c Levels in Elderly Patients with Diabetes. AB - AIM: to obtain information on the proportion of orthostatic hypotension in elderly patients with diabetes and its relationship with HbA1c levels. METHODS: this is a cross-sectional study on 350 patients with diabetes mellitus (DM) aged 60 years old who sought treatment at outpatient clinic of Geriatry and Diabetes Division at Cipto Mangunkusumo Hospital between January and March 2016. Orthostatic hypotension was defined as a decrease in systolic blood pressure 20 mmHg and/or diastolic pressure 10 mmHg within 3 minutes after changing position from lying to standing. HbA1c levels was measured using Nycocard from Axis Shield. Chi square test was used for bivariate analysis and logistic regression was used for multivariate analysis against confounding variables. RESULTS: the proportion of orthostatic hypotension in elderly subjects with DM was 27.4%. Median of HbA1c levels was higher in subjects with than without orthostatic hypotension (7.6% vs. 7.1%; p<0.05). There was an association between HbA1c levels of 7.35% and the incidence of orthostatic hypotension (OR 1.987, 95% CI 1.2-3.2). The duration of having DM was a confounding variable. CONCLUSION: orthostatic hypotension is more common in elderly subjects with DM. There is an association between the incidence of orthostatic hypotension and increased HbA1c levels in elderly patients with diabetes mellitus. PMID- 27550882 TI - Obstructive Jaundice as a Complication of Macrocystic Serous Cystadenoma of the Pancreas. AB - Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Herein, we report on a 40-year-old woman diagnosed with macrocystic serous cystadenoma who presented with obstructive jaundice. A cystic lesion in the head and body of the pancreas was revealed by abdominal computed tomography. Intraoperative pancreatic cyst aspiration ruled out mucinous cystic neoplasm which has a malignant potential. The pancreatic cyst fluid cytology was basophilic amorph materials concluded as benign cystic lesion. Internal drainage was performed instead of pancreatic resection which showed good outcome. Biliary obstruction is a rare complication of serous cystadenoma. This case describes an unusual clinical presentation of macrocystic serous cystadenoma. PMID- 27550883 TI - Chemotherapy-induced Spontaneous Pneumothorax: Case Series. AB - We present 2 patients who developed spontaneous pneumothorax (SP) following rapid regression of lymphoma and rhabdomyosarcoma with lung metastases. Case 1, a 43 year old man was admitted to our hospital with dyspnea 10 days before admission. He denied any recent trauma or previous treatment for lung tuberculosis. Three weeks prior to admission, he received first cycle of CHOP for non-Hodgkin's lymphoma stage II BE. Chest X-ray consistent with right pneumothorax. After treatment with chest tube drainage for about 1 month, the patient recovered and chemotherapy could be continued without further complications. Case 2, a 35- year old man was admitted to other hospital with dyspnea and chest pain on day 4 after second cycle of systemic combined chemotherapy for rhabdomyosarcoma stage IV (lung metastases) with doxorubicin, ifosfamide, mesna, and dacarbazine. Chest X ray showed hydropneumothorax on right and left lung. After treatment with chest tube drainage about 2 weeks, the patient recovered and chemotherapy could be continued without further complications. The mechanism of pneumothorax following chemotherapy is not clearly understood yet, however, several hypotheses have been considered: 1) the rupture of a subpleural bulla after chemotherapy; 2) the rupture of an emphysematous bulla in an over expanded portion of the lung which is partially obstructed by a neoplasm; 3) tumor lyses or necrosis due to cytotoxic chemotherapy directly induces the formation of fistula. Dyspnea and chest pain suddenly appear during successful chemotherapy for metastatic chemosensitive tumors should alert the physician to the possibility of SP. The treatment is directed toward lung re-expansion. Chemotherapy induced pneumothorax should be considered as oncologic emergency. PMID- 27550884 TI - New Paradigm in Treating Cancer: Right on Target. AB - Cancer prevalence is increasing every year and now cancer is the third highest cause of death in developing countries. Effective anticancer treatment can prolong life and improve the patient's quality of life. Targeted therapy is a new therapeutic modality which targets specific molecules in the cancer cell and disrupts dysregulated signaling pathways involved in carcinogenesis. Since targeted therapy does not attack normal cells, its side effects are considered low compared to chemotherapy. More than 15 drugs have been approved for treatment in various human cancers. These drugs can largely be grouped into tyrosine kinase inhibitors and monoclonal antibodies. This review will focus on the most common agents within both groups. PMID- 27550885 TI - Improvement of Metabolic Parameters Resulted from Levothyroxine Therapy in Hypothyroid Type 2 Diabetes Mellitus Patient. AB - This is a case of 51 year-old woman with uncontrolled type 2 diabetes mellitus which was diagnosed 1.5 year earlier, obesity with body mass index 32.2 kg/m2, waist circumference of 113 cm, diffuse goiter with neck circumference 40 cm, and hypertension with blood pressure >140/90 mmHg. Since 6 months ago, she often seemed like having less concentration or daydreaming, chronic fatigue, depression, and low food intake. Her body weight had been increasing over time. Her hypothyroidism clinical scoring Billewicz and Zulewski criterias were 17 and 8 respectively, showing that she tended to experience hypothyroidism. From laboratory examination, fasting blood glucose was 216 mg/dL and 2-hour postprandial blood glucose was 320 mg/dL with level of HbA1c was 9.9%, triglyceride level was 486 mg/dL, HDL cholesterol 46 mg/dL, LDL cholesterol 157 mg/dL, and total cholesterol was 269 mg/dL. Thyroid ultrasound showed a diffuse goiter in both lobes of her thyroid gland. PMID- 27550886 TI - Colloids Versus Albumin in Large Volume Paracentesis to Prevent Circulatory Dysfunction: Evidence-based Case Report. AB - Large volume paracentesis may cause paracentesis induced circulatory dysfunction (PICD). Albumin is recommended to prevent this abnormality. Meanwhile, the price of albumin is too expensive and there should be another alternative that may prevent PICD. This report aimed to compare albumin to colloids in preventing PICD. Search strategy was done using PubMed, Scopus, Proquest, dan Academic Health Complete from EBSCO with keywords of "ascites", "albumin", "colloid", "dextran", "hydroxyethyl starch", "gelatin", and "paracentesis induced circulatory dysfunction". Articles was limited to randomized clinical trial and meta-analysis with clinical question of "In hepatic cirrhotic patient undergone large volume paracentesis, whether colloids were similar to albumin to prevent PICD". We found one meta-analysis and four randomized clinical trials (RCT). A meta analysis showed that albumin was still superior of which odds ratio 0.34 (0.23-0.51). Three RCTs showed the same results and one RCT showed albumin was not superior than colloids. We conclude that colloids could not constitute albumin to prevent PICD, but colloids still have a role in patient who undergone paracentesis less than five liters. PMID- 27550887 TI - Diagnosis and Management of Infections Caused by Enterobacteriaceae Producing Extended-Spectrum b-Lactamase. AB - Bacterial resistance to antibiotics is a serious problem worldwide that affect the increment of morbidity and mortality rate; Enterobacteriaceae producing ESBL is one of the causes. However, there are still limited information regarding diagnosis and management of ESBL-E infection. Detection of ESBL-E requires certain steps that are problematic and time consuming. Diagnosis and management of ESBL-E infection have become more and more challenging due to limited diagnostic method available and choice of antibiotics that may be used, along with growing subtyped of ESBL through various of mutations. This article is aimed to give an overview on current situation of ESBL-E infections, with a focus on diagnosis and management of such infection by reviewing several recent studies on related issue. PMID- 27550888 TI - Factors influencing intention to help and helping behaviour in witnesses of bullying in nursing settings. AB - The role played by witnesses of bullying in nursing settings remains little studied, despite their potential relevance in explaining the onset and development of bullying. The objective of this study was to develop a model to account for witnesses' intention to help and helping behaviour in response to bullying in a nursing setting. Three hundred and thirty-seven witnesses completed self-report measures of variables predicting intention to help and helping behaviour. A full structural model was constructed using structural equation modelling. The intention to help victims was elicited by tension, group identity, support to peers' initiative to intervene and absence of fear of retaliation. However, engagement in helping behaviour was only predicted by the absence of fear of retaliation. This study shows that witnesses of bullying in nursing settings do not remain impassive, but their experienced discomfort and intention to help victims is not sufficient to predict helping behaviour. Fear of possible retaliation if intervening in favour of victims constitutes a crucial factor explaining witnesses' hesitation to help victims. Several implications for the implementation of policies directed at eradicating bullying in nursing settings are discussed. PMID- 27550889 TI - Sibling sexual abuse: why don't we talk about it? AB - AIMS AND OBJECTIVES: To explore two hypotheses for explaining why there is little written about sibling sexual abuse and to raise awareness of the subject in order better to protect children and to facilitate sensitive patient care. BACKGROUND: While there is no universal agreement over its definition, sibling sexual abuse is acknowledged internationally as a prevalent form of child sexual abuse but tends not to be recognised by health professionals. It is also under-represented within the literature in comparison with other forms of intrafamilial sexual abuse. Understanding why this is may help to illuminate the potential barriers to effective professional responses. Two explanations which emerge strongly are the existence of a sibling incest taboo and a prevailing belief that sibling sexual behaviour is largely harmless. DESIGN: Discursive position paper. METHOD: The paper examines the two hypotheses through exploration of the extant literature on sibling incest and sibling sexual abuse. CONCLUSIONS: Sibling sexual abuse accounts for a significant minority of child sexual abuse and has the potential to be as harmful as sexual abuse by a parent. An abhorrence at the thought of sibling sexual activity and a prevailing view of its harmlessness may hinder nurses' detection of and appropriate responses to sibling sexual abuse, but do not provide convincing explanations for the dearth of literature. Instead, a deeply held perspective of sibling relationships as non-abusive offers a more profound explanation. RELEVANCE TO CLINICAL PRACTICE: A knowledge of sibling sexual abuse and its consequences are important both for the effective protection of children and the sensitive and appropriate treatment of patients who present with a variety of physical and mental health concerns. A perspective that sibling relationships are non-abusive provides a deeper level of understanding of the powerful obstacles to raising awareness of and responding appropriately to this form of abuse. PMID- 27550890 TI - Safety and Efficacy of Stosstherapy in Nutritional Rickets. AB - OBJECTIVE: Stosstherapy has been used since early 19th century for treating nutritional rickets. However, there are no clear cut guidelines for the biochemical monitoring of this treatment. Repeated blood tests at short intervals increase the cost of therapy and noncompliance. METHODS: A prospective study was conducted on 191 cases of nutritional rickets below 10 years of age to evaluate the effectivity of stosstherapy. All cases were treated with a single intramuscular injection of vitamin D (600.000 IU) along with oral calcium (50 mg/kg) and vitamin D (400 IU per day) until radiological resolution. Dietary modifications and adequate sunlight exposure were also recommended. RESULTS: The mean age of presentation was 2 years 9 months. Mean sunlight exposure was 17 minutes/week with 90% having low sunlight exposure (<30 minutes/week). Prolonged breast feeding (>6 months) was found in 93.7% of the cases. With treatment, the clinical features started resolving by 1 month with complete resolution of most of the features over a period of 1 year. By 6 months, all the study subjects had complete radiological resolution. Serum levels of calcium and alkaline phosphatase (ALP) were restored by 6 months in most cases while phosphate and vitamin D levels normalized by 6 weeks. CONCLUSION: Stosstherapy is a safe, cheap and effective method of treating nutritional rickets. Biochemical tests at initial presentation followed by vitamin D assay at 6 weeks and calcium, phosphate and ALP assays at 6 months is recommended in the monitoring of these patients. For regular monitoring, only ALP assay is recommended, provided one abstains from repeat injection of vitamin D based on high ALP levels. PMID- 27550891 TI - Pediatric multiple sclerosis: The 2015 Sydney Carter Award Lecture. PMID- 27550892 TI - Blue Consciousness. PMID- 27550893 TI - Transient deficits after inadvertent intrathecal trigger-point injection with lidocaine. PMID- 27550895 TI - Irena Hausmanowa-Petrusewicz, MD, PHD (1917-2015). PMID- 27550894 TI - The "seagull cry": An initial sign in a child with intracranial carotid stenosis. PMID- 27550896 TI - Cause of death and predictors of mortality in a community-based cohort of people with epilepsy. PMID- 27550897 TI - Clinical Reasoning: A 33-year-old man with cardiomyopathy and myopathy. PMID- 27550898 TI - Pearls & Oy-sters: Niemann-Pick disease type C in a 65-year-old patient. PMID- 27550899 TI - Teaching NeuroImages: Aphasia after infarction of the left pulvinar nucleus. PMID- 27550900 TI - Teaching NeuroImages: Usefulness of susceptibility-weighted sequences after traumatic brain injury. PMID- 27550901 TI - China's shift from population control to population quality: Implications for neurology. PMID- 27550902 TI - Coupling of Excitons and Discrete Acoustic Phonons in Vibrationally Isolated Quantum Emitters. AB - The photoluminescence emission by mesoscopic condensed matter is ultimately dictated by the fine-structure splitting of the fundamental exciton into optically allowed and dipole-forbidden states. In epitaxially grown semiconductor quantum dots, nonradiative equilibration between the fine-structure levels is mediated by bulk acoustic phonons, resulting in asymmetric spectral broadening of the excitonic luminescence. In isolated colloidal quantum dots, spatial confinement of the vibrational motion is expected to give rise to an interplay between the quantized electronic and phononic degrees of freedom. In most cases, however, zero-dimensional colloidal nanocrystals are strongly coupled to the substrate such that the charge relaxation processes are still effectively governed by the bulk properties. Here we show that encapsulation of single colloidal CdSe/CdS nanocrystals into individual organic polymer shells allows for systematic vibrational decoupling of the semiconductor nanospheres from the surroundings. In contrast to epitaxially grown quantum dots, simultaneous quantization of both electronic and vibrational degrees of freedom results in a series of strong and narrow acoustic phonon sidebands observed in the photoluminescence. Furthermore, an individual analysis of more than 200 compound particles reveals that enhancement or suppression of the radiative properties of the fundamental exciton is controlled by the interaction between fine-structure states via the discrete vibrational modes. For the first time, pronounced resonances in the scattering rate between the fine-structure states are directly observed, in good agreement with a quantum mechanical model. The unambiguous assignment of mediating acoustic modes to the observed scattering resonances complements the experimental findings. Thus, our results form an attractive basis for future studies on subterahertz quantum opto-mechanics and efficient laser cooling at the nanoscale. PMID- 27550903 TI - Intron Length Coevolution across Mammalian Genomes. AB - Although they do not contribute directly to the proteome, introns frequently contain regulatory elements and can extend the protein coding potential of the genome through alternative splicing. For some genes, the contribution of introns to the time required for transcription can also be functionally significant. We have previously shown that intron length in genes associated with developmental patterning is often highly conserved. In general, sets of genes that require precise coordination in the timing of their expression may be sensitive to changes in transcript length. A prediction of this hypothesis is that evolutionary changes in intron length, when they occur, may be correlated between sets of coordinately expressed genes. To test this hypothesis, we analyzed intron length coevolution in alignments from nine eutherian mammals. Overall, genes that belong to the same protein complex or that are coexpressed were significantly more likely to show evidence of intron length coevolution than matched, randomly sampled genes. Individually, protein complexes involved in the cell cycle showed the strongest evidence of coevolution of intron lengths and clusters of coexpressed genes enriched for cell cycle genes also showed significant evidence of intron length coevolution. Our results reveal a novel aspect of gene coevolution and provide a means to identify genes, protein complexes and biological processes that may be particularly sensitive to changes in transcriptional dynamics. PMID- 27550904 TI - The Effects of Population Size Histories on Estimates of Selection Coefficients from Time-Series Genetic Data. AB - Many approaches have been developed for inferring selection coefficients from time series data while accounting for genetic drift. These approaches have been motivated by the intuition that properly accounting for the population size history can significantly improve estimates of selective strengths. However, the improvement in inference accuracy that can be attained by modeling drift has not been characterized. Here, by comparing maximum likelihood estimates of selection coefficients that account for the true population size history with estimates that ignore drift by assuming allele frequencies evolve deterministically in a population of infinite size, we address the following questions: how much can modeling the population size history improve estimates of selection coefficients? How much can mis-inferred population sizes hurt inferences of selection coefficients? We conduct our analysis under the discrete Wright-Fisher model by deriving the exact probability of an allele frequency trajectory in a population of time-varying size and we replicate our results under the diffusion model. For both models, we find that ignoring drift leads to estimates of selection coefficients that are nearly as accurate as estimates that account for the true population history, even when population sizes are small and drift is high. This result is of interest because inference methods that ignore drift are widely used in evolutionary studies and can be many orders of magnitude faster than methods that account for population sizes. PMID- 27550905 TI - Yoga for metabolic syndrome: A systematic review and meta-analysis. AB - Background Metabolic syndrome is the most important risk factor for developing cardiovascular disease and type 2 diabetes. The aim of this review was to systematically assess and perform a meta-analysis of the effects of yoga on the parameters of metabolic syndrome. Methods MEDLINE/PubMed, Scopus, the Cochrane Central Register of Controlled Trials and IndMED were searched and screened from their inception through to 8 March 2016 for randomised controlled trials on yoga for patients with metabolic syndrome. Risk of bias was assessed using the Cochrane risk of bias tool. Results Seven trials with a total of 794 participants were included. No effects of yoga on resolution of metabolic syndrome, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and fasting plasma glucose were found, but yoga was superior to usual care for waist circumference (standardised mean difference (SMD) = -0.35; 95% confidence interval (CI) = -0.57 to -0.13; p < 0.01) and systolic blood pressure (SMD = 0.29; 95% CI = -0.51 to -0.07; p = 0.01). However, these effects were not robust against selection bias. No intervention-related adverse events were reported. Conclusion Based on the results of this meta-analysis, no recommendation can be made for or against yoga in order to influence the parameters of metabolic syndrome. Despite methodological drawbacks, and until further research is undertaken, yoga can be preliminarily considered as a safe and effective intervention for reducing waist circumference and systolic blood pressure in individuals with metabolic syndrome who are not adhering to conventional forms of exercise. PMID- 27550906 TI - Supervised exercise training in peripheral arterial disease increases vascular shear stress and profunda femoral artery diameter. AB - Background Arteriogenesis is promoted by flow- and pressure-related forces such as tangential wall stress and laminar shear stress. Exercise training (ET) is known to promote arteriogenesis in peripheral arterial disease (PAD) patients. It remains unclear whether supervised ET (SET) promotes arteriogenesis more efficiently than non-SET (nSET). Methods and results Forty PAD patients participated in a SET or nSET training programme ( n = 20 each) and were compared to 20 healthy individuals without any history of cardiovascular events. Femoral artery diameter, flow and velocity were measured by ultrasound. Tangential wall stress and laminar shear stress were calculated for femoral arteries. Follow-up was performed after a mean of 7.65 +/- 1.62 months. At follow-up, only the SET group showed a significant increase in lumen diameter of the profunda femoral artery ( p = 0.03), accompanied by an increase of tangential wall stress ( p = 0.002). Laminar shear stress decreased, but remained higher for the SET group compared to controls ( p < 0.01). Individual changes in walking distance were higher for SET patients ( p = 0.01) than nSET patients ( p = 0.07). Profunda femoral lumen diameter and tangential wall stress correlated directly with walking distance ( r = 0.446; p < 0.001), as well as with each other ( r = 0.743; p < 0.0001). Conclusions Our results indicate that SET promotes arteriogenesis more efficiently than nSET. Femoral lumen diameter and flow might help with the monitoring of ET efficiency and potential arteriogenesis. PMID- 27550907 TI - Association between carotid intima-media thickness and adiponectin in participants without diabetes or cardiovascular disease of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). AB - Objective The study assessed the association of adiponectin concentration with carotid intima-media thickness (CIMT) in middle-aged participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease. Design Cross-sectional analyses. Methods A sample of 687 individuals (35-54 years old) without diabetes or cardiovascular disease was stratified into two categories according to CIMT (< or >= 75th percentile). Traditional risk factors, C-reactive protein and adiponectin values were compared between categories by Student's t-test and frequencies by chi-square test. In linear regression models, associations of CIMT with adiponectin, adjusted for adiposity, blood pressure, C-reactive protein and homeostasis model assessment insulin resistance were tested. Mean CIMT values were compared across quartiles of adiponectin concentrations using analysis of variance. Results Three hundred and forty-one individuals (49.6%) were women and 130 (19.0%) had three traditional cardiovascular risk factors. Those with elevated CIMT (21.8%) had greater mean values of body mass index (26.2(3.8) vs. 27.7(4.0)kg/m2, p < 0.001), waist circumference (86.9(10.1) vs. 90.1(10.8) cm, p = 0.001), systolic blood pressure (116.2(13.6) vs.121.2(16.1) mmHg, p < 0.001), homeostasis model assessment index (1.4(0.9-2.4) vs. 1.8(1.1-2.9), p = 0.011), C-reactive protein (1.2 (0.6-2.6) vs. 1.4(0.8-3.2) mg/l, p = 0.054) and adiponectin (9.9 (6.0-14.7) vs. 8.9 (5.3-13.8) ug/ml, p = 0.002) levels than the counterpart, while plasma glucose and lipids were not different between groups. In the adjusted model, blood pressure (directly) and adiponectin (inversely) persisted associated with high CIMT. Mean CIMT was greater in the first quartile of adiponectin when compared with the other three quartiles ( p = 0.019). Conclusions Lower adiponectin levels together with higher blood pressure were independently associated with elevated CIMT. Adiponectin concentration may be an independent marker of early structural damage in individuals at low-to-moderate cardiovascular risk. PMID- 27550908 TI - Asbestos bodies in bronchoalveolar lavage in the 21st century: a time-trend analysis in a clinical population. AB - OBJECTIVES: Asbestos bodies (AB) in bronchoalveolar lavage (BAL) can be detected by light microscopy and their concentration is indicative of past cumulative asbestos exposure. We assessed clinical and exposure characteristics, as well as possible time trends, among patients in whom AB had been quantified in BAL. METHODS: BAL samples obtained from 578 participants between January 1997 and December 2014 were available for analysis. The processing of samples and the microscopic analysis were performed by a single expert and 76% of samples came from a single tertiary care hospital, allowing clinical and exposure data to be extracted from patient files. RESULTS: The study population (95% males) had a mean age of 62.5 (+/-12.4) years. AB were detected in 55.2% of the samples, giving a median concentration of 0.5 AB/mL (95th centile: 23.6 AB/mL; highest value: 164.5 AB/mL). The AB concentration exceeded 1 AB/mL in 39.4% and 5 AB/mL in 17.8%. A significant decrease from a geometric mean of 0.93 AB/mL in 1997 to 0.2 AB/mL in 2014 was apparent. High AB concentrations generally corresponded with occupations with (presumed) high asbestos exposure. AB concentrations were higher among patients with asbestosis and pleural plaques, when compared with other disease groups. Nevertheless, a substantial proportion of participants with likely exposure to asbestos did not exhibit high AB counts. CONCLUSIONS: This retrospective study of a large clinical population supports the value of counting AB in BAL as a complementary approach to assess past exposure to asbestos. PMID- 27550909 TI - Work injuries among migrant workers in Denmark. AB - OBJECTIVES: Work migration into Denmark has increased during the recent decades, especially after the enlargement of the European Union (EU) in 2004. Whether or not migrant workers experience more work injuries than the native workforce has been debated and results are conflicting, most likely due to methodological difficulties and cultural disparities. We set out to meet these challenges using population-based work injury registers, targeting a specific and representative region in Denmark. METHODS: This population-based study used data on work injuries from an emergency department (ED) and reported injuries from the ED's catchment area to the Danish Working Environment Authority during 11 years. We calculated incidences of work injury for groups of migrant workers compared with native Danes and adjusted incidence rate ratios based on information on the complete working population. RESULTS: The incidences of work injuries among migrant workers from the new EU countries and from the rest of the world were higher compared with Danish workers and workers from the old EU countries and other Western countries. Especially migrants older than 30 years and in low-risk industries were at higher risk. Workers who had migrated recently were at even higher risk. CONCLUSIONS: We found increased risk of work injuries among migrant workers. Studying migrants in registers is a methodological challenge as some migrants are not registered, for legal or illegal reasons; thus, only a selected group is studied, but this may most likely underestimate the risk. PMID- 27550910 TI - A Cross-National Comparison of Attributional Patterns Toward Students With and Without Learning Disabilities. AB - Claims of the importance of having positive perceptions and expectations of students with learning disabilities (LD) have been repeatedly made over recent years. This article aims to raise awareness of the importance of attributional beliefs in relation to the educational outcomes of students with LD in Australia and China. Australian and Chinese trainee teachers ( N = 240) who were at the end of their training were surveyed with vignettes and Likert-scale questions to ascertain their responses to students with and without LD. Overall, the findings suggest that Chinese trainee teachers' attributional pattern is more positive than that of their Australian counterparts. Implications and recommendations for research and practice are also presented. PMID- 27550911 TI - Poor Reliability of Wrist Blood Pressure Self-Measurement at Home: A Population Based Study. AB - The reliability of blood pressure measurement with wrist devices, which has not previously been assessed under real-life circumstances in general population, is dependent on correct positioning of the wrist device at heart level. We determined whether an error was present when blood pressure was self-measured at the wrist in 721 unselected subjects from the general population. After training, blood pressure was measured in the office and self-measured at home with an upper arm device (the UA-767 Plus) and a wrist device (the UB-542, not provided with a position sensor). The upper-arm-wrist blood pressure difference detected in the office was used as the reference measurement. The discrepancy between office and home differences was the home measurement error. In the office, systolic blood pressure was 2.5% lower at wrist than at arm (P=0.002), whereas at home, systolic and diastolic blood pressures were higher at wrist than at arm (+5.6% and +5.4%, respectively; P<0.0001 for both); 621 subjects had home measurement error of at least +/-5 mm Hg and 455 of at least +/-10 mm Hg (bad measurers). In multivariable linear regression, a lower cognitive pattern independently determined both the systolic and the diastolic home measurement error and a longer forearm the systolic error only. This was confirmed by logistic regression having bad measurers as dependent variable. The use of wrist devices for home self-measurement, therefore, leads to frequent detection of falsely elevated blood pressure values likely because of a poor memory and rendition of the instructions, leading to the wrong position of the wrist. PMID- 27550913 TI - An Ecosystem to Support Traditional Clinical Investigation: Lessons From Aging, Exercise, Blood Pressure, and Women. PMID- 27550912 TI - Developmental Programming of Hypertension: Physiological Mechanisms. PMID- 27550914 TI - The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial). AB - The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned "less tight" (target diastolic 100 mm Hg) and "tight" (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, -$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, -$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, -$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412. PMID- 27550915 TI - Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease. AB - Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49-7.7; P=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e' ratio (95% confidence interval, 1.0-16; P=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0-12; P=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD. PMID- 27550916 TI - Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice. AB - Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8+/-1.5 mm Hg in sham versus 96.6+/-6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model. PMID- 27550917 TI - A Disintegrin and Metalloprotease-17 Regulates Pressure Overload-Induced Myocardial Hypertrophy and Dysfunction Through Proteolytic Processing of Integrin beta1. AB - A disintegrin and metalloprotease-17 (ADAM17) belongs to a family of transmembrane enzymes, and it can mediate ectodomain shedding of several membrane bound molecules. ADAM17 levels are elevated in patients with hypertrophic and dilated cardiomyopathy; however, its direct role in hypertrophic cardiomyopathy is unknown. Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17(flox/flox)/alphaMHC-Cre; ADAM17(f/f)/Cre) and littermates with intact ADAM17 levels (ADAM17(f/f)) were subjected to cardiac pressure-overload by transverse aortic constriction. Cardiac function/architecture was assessed by echocardiography at 2 and 5 weeks post transverse aortic constriction. ADAM17 knockdown enhanced myocardial hypertrophy, fibrosis, more severe left ventricular dilation, and systolic dysfunction at 5 weeks post transverse aortic constriction. Pressure overload-induced upregulation of integrin beta1 was much greater with ADAM17 knockdown, concomitant with the greater activation of the focal adhesion kinase pathway, suggesting that integrin beta1 could be a substrate for ADAM17. ADAM17 knockdown did not alter other cardiomyocyte integrins, integrin alpha5 or alpha7, and HB-EGF (heparin-bound epidermal growth factor), another potential substrate for ADAM17, remained unaltered after pressure overload. ADAM17-mediated cleavage of integrin beta1 was confirmed by an in vitro assay. Intriguingly, ADAM17 knockdown did not affect the myocardial hypertrophy induced by a subpressor dose of angiotensin II, which occurs independent from the integrin beta1-mediated pathway. ADAM17-knockdown enhanced the hypertrophic response to cyclic mechanical stretching in neonatal rat cardiomyocytes. This study reports a novel cardioprotective function for ADAM17 in pressure overload cardiomyopathy, where loss of ADAM17 promotes hypertrophy by reducing the cleavage of cardiac integrin beta1, a novel substrate for ADAM17. This function of ADAM17 is selective for pressure overload-induced myocardial hypertrophy and dysfunction, and not agonist-induced hypertrophy. PMID- 27550918 TI - Rapid Early Growth May Modulate the Association Between Birth Weight and Blood Pressure at 5 Years in the EDEN Cohort Study. AB - Physiological evidence suggests that birth weight (BW) and postnatal growth affect blood pressure (BP) level, independently or in interaction. Their respective roles are difficult to disentangle in epidemiological studies, however, especially when adjusting for final weight. We assessed the portion of the effect of BW on BP at 5 years that was not attributable to postnatal growth and investigated potential interactions between BW and postnatal growth velocity at different time points in the EDEN mother-child study. Collecting a median of 19 weight measurements for each of the 1119 children who completed follow-up enabled us to model instantaneous growth velocity at any age. After computing a BP SD-score at 5 years, adjusted for age, sex, current body mass index, and height, we used multiple linear regression to study its association with age- and sex-specific BW z score, adjusting for several maternal and pregnancy risk factors. We tested interactions between BW categories (small-, appropriate-, and large-for-gestational-age) and weight growth velocities at different ages. The BW z score was negatively and significantly correlated with the systolic BP SD-score at the age of 5 years (r=-0.07, P=0.02). Interactions were found between BW categories and weight growth velocities from 1 to 4 months (P from 0.002 to 0.08) but not at older ages; specifically, children born small for gestational age with a fast weight growth velocity in their first few months of life had the highest absolute systolic BP and SD score values at 5 years. They may need monitoring for cardiovascular risks. PMID- 27550919 TI - Natural Killer Cell Reduction and Uteroplacental Vasculopathy. AB - Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen*male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth. PMID- 27550920 TI - Heteromerization Between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences. AB - Bradykinin B2 receptor (B2R) and angiotensin-(1-7) Mas receptor (MasR)-mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R-MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R-MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R-MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal-regulated kinase phosphorylation after angiotensin-(1-7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R-MasR but not in B2R-expressing cells. Angiotensin-(1-7) and bradykinin elicited antiproliferative effects only in cells expressing B2R-MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R-MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1-7) MasR-mediated effects. B2R-MasR heteromerization induces functional changes in the receptor that may lead to long lasting protective properties. PMID- 27550921 TI - Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening: The Maastricht Study. AB - Arterial stiffening, as characterized by an increase in carotid-femoral pulse wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (sbeta 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (sbeta 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus. PMID- 27550922 TI - Early Postmenopausal Phase Is Associated With Reduced Prostacyclin-Induced Vasodilation That Is Reversed by Exercise Training: The Copenhagen Women Study. AB - The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1+/-0.5 [mean+/-SE] years after final menstrual period) women only separated by 4 (50+/-0 versus 54+/-1) years of age were included. Before the training period, the vasodilator response to intra-arterial infusion of either the prostacyclin analog epoprostenol or acetylcholine was lower (~13% 41%; P<0.05) in the postmenopausal compared with the premenopausal women. Acetylcholine infusion induced a similar release of prostacyclin (6-keto prostaglandin F1a). To elucidate the role of vasoconstrictor prostanoids, acetylcholine infusion was combined with the cyclooxygenase inhibitor ketorolac and here the vascular response to acetylcholine was reduced to a similar extent in pre- and postmenopausal women. Exercise training increased (P<0.05) the vasodilator response to epoprostenol (~100%-150%) and acetylcholine (~100%-120%) infusion in the postmenopausal group. These findings demonstrate that the early postmenopausal phase is associated with a marked reduction in vascular function. Despite of a reduced sensitivity to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent postmenopausal women. PMID- 27550924 TI - Reply to: Danoprevir pharmacokinetic/viral kinetic model for treating chronic HCV - some considerations. PMID- 27550923 TI - Progression of Chronic Kidney Disease After Acute Kidney Injury: Role of Self Perpetuating Versus Hemodynamic-Induced Fibrosis. AB - The relative contribution of self-perpetuating versus hemodynamic-induced fibrosis to the progression of chronic kidney disease (CKD) after acute kidney injury (AKI) is unclear. In the present study, male Sprague-Dawley rats underwent right uninephrectomy and were instrumented with a blood pressure radiotelemeter. Two weeks later, separate groups of rats were subjected to 40 minutes renal ischemia-reperfusion or sham surgery and followed up for 4 or 16 weeks to determine the extent to which glomerulosclerosis and tubulointerstitial fibrosis as a result of the AKI-CKD transition (ie, at 4 weeks post AKI) change over time during the progression of CKD (ie, at 16 weeks post AKI). On average, tubulointerstitial fibrosis was ~3-fold lower (P<0.05), whereas glomerulosclerosis was ~6-fold higher (P<0.05) at 16 versus 4 weeks post AKI. At 16 weeks post AKI, marked tubulointerstitial fibrosis was only observed in rats exhibiting marked glomerulosclerosis, proteinuria, and kidney hypertrophy consistent with a hemodynamic pathogenesis of renal injury. Moreover, quantitative analysis between blood pressure and renal injury revealed a clear and modest blood pressure threshold (average 16-week systolic blood pressure of ~127 mm Hg) for the development of glomerulosclerosis. In summary, modest levels of blood pressure may be playing a substantial role in the progression of renal disease after AKI in settings of preexisting CKD associated with 50% loss of renal mass. In contrast, these data do not support a major role of self perpetuating tubulointerstitial fibrosis in the progression CKD after AKI in such settings. PMID- 27550926 TI - Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis. AB - The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori's trichrome, immunohistochemistry of collagen type I, TGF-beta1, beta-prolyl-4 hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-beta1 and beta-prolyl-4-hydroxylase and an increase of metalloproteinase -1, -2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis. PMID- 27550927 TI - Danoprevir pharmacokinetic/viral kinetic model for treating chronic HCV - some considerations. PMID- 27550928 TI - Os Trigonum Excision in Dancers via an Open Posteromedial Approach. AB - BACKGROUND: An os trigonum is a potential source of posterior ankle pain in dancers, often associated with flexor hallucis longus (FHL) pathology. Options for operative excision include open excision, subtalar arthroscopy, and posterior endoscopy. The purpose of this paper was to present a series of dancers who underwent excision of a symptomatic os trigonum via an open posteromedial approach. METHODS: This study is a retrospective case series of 40 ankles in 38 dancers who underwent os trigonum excision via an open posteromedial approach with FHL tenolysis between 2000 and 2013. All patients were interviewed and charts retrospectively analyzed. Collected variables included pre- and postoperative pain level, time to return to dance, and subjective satisfaction. The average age was 19.2 years; ballet was the primary dance form in 36 (95%) of patient-cases. Eight (20%) of the patient-cases were professional dancers, and 30 (75%) were students or preprofessional dancers. RESULTS: Average preoperative pain level was 7.7/10, which decreased to 0.6/10 postoperatively. Seventeen (42.5%) experienced concurrent preoperation-associated FHL symptomatology, all of whom experienced relief postoperatively. The average time to return to dance was 7.9 weeks, and time to pain-free dance was 17.7 weeks. Of the 37 patient-cases desiring to return to dance, 35 (94.6%) returned to their preoperative level of dance. There were no neurovascular or other major complications. Four (10%) had minor wound complications that resolved, and 38 cases (95%) considered the procedure a success. CONCLUSION: Open posteromedial excision of an os trigonum in dancers provided satisfactory pain relief, return to dance, and complication rates compared to other approaches, and allowed for identifying and treating any associated FHL pathology. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 27550925 TI - Original Research: Featured Article: Imatinib mesylate (Gleevec) inhibits Notch and c-Myc signaling: Five-day treatment permanently rescues mammary development. AB - Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment. In addition, these mice do not develop mammary tumors. We investigated the mechanism for Gleevec regulation of Notch signaling and found that Gleevec treatment results in a loss of Int3 protein but not of Int3 mRNA in HC11 mouse mammary epithelial cells expressing Int3. The addition of MG-132, a proteasome inhibitor, shows increased ubiquitination of Int3 in the presence of Gleevec. Thus, Gleevec affects the stability of Int3 by promoting the degradation of Int3 via E3 ubiquitin ligases targeting it for the proteasome degradation. Gleevec is a tyrosine kinase inhibitor that acts on c-Kit and PDGFR. Therefore, we investigated the downstream substrate kinase GSK3beta to ascertain the possible role that this kinase might play in the stability of Int3. Data show that Gleevec degradation of Int3 is GSK3beta dependent. We have expanded our study of the effects Gleevec has on tumorigenesis of other oncogenes. We have found that anchorage-independent growth of HC11-c-Myc cells as well as tumor growth in nude mice is inhibited by Gleevec treatment. As with Int3, Gleevec treatment appears to destabilize the c-Myc protein but not mRNA. These results indicate that Gleevec could be a potential therapeutic drug for patients bearing Notch4 and/or c-Myc positive breast carcinomas. PMID- 27550929 TI - Self-driven perfusion culture system using a paper-based double-layered scaffold. AB - Shear stress caused by fluid flow is known to promote tissue development from cells in vivo. Therefore, perfusion cultures have been studied to investigate the mechanisms involved and to fabricate engineered tissues in vitro, particularly those that include blood vessels. Microfluidic devices, which function with fine machinery of chambers and microsyringes for fluid flow and have small culture areas, are conventionally used for perfusion culture. In contrast, we have developed a self-driven perfusion culture system by using a paper-based double layered scaffold as the fundamental component. Gelatin microfibers were electrospun onto a paper material to prepare the scaffold system, in which the constant perfusion of the medium and the scaffold for cell adhesion/proliferation were functionally divided into a paper and a gelatin microfiber layer, respectively. By applying both the capillary action and siphon phenomenon of the paper-based scaffold, which bridged two medium chambers at different height levels, a self-driven medium flow was achieved and the flow rate was also stable, constant, and quantitatively controllable. Moreover, the culture area was enlargeable to the cm(2) scale. The endothelial cells cultivated on this system oriented along the medium-flow direction, suggesting that the shear stress caused by medium flow was effectively applied. This perfusion culture system is expected to be useful for fabricating three-dimensional and large engineered tissues in the future. PMID- 27550930 TI - Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C. AB - Native small intestine possesses distinct multi-scale structures (e.g., crypts, villi) not included in traditional 2D intestinal culture models for drug delivery and regenerative medicine. The known impact of structure on cell function motivates exploration of the influence of intestinal topography on the phenotype of cultured epithelial cells, but the irregular, macro- to submicron-scale features of native intestine are challenging to precisely replicate in cellular growth substrates. Herein, we utilized chemical vapor deposition of Parylene C on decellularized porcine small intestine to create polymeric intestinal replicas containing biomimetic irregular, multi-scale structures. These replicas were used as molds for polydimethylsiloxane (PDMS) growth substrates with macro to submicron intestinal topographical features. Resultant PDMS replicas exhibit multiscale resolution including macro- to micro-scale folds, crypt and villus structures, and submicron-scale features of the underlying basement membrane. After 10 d of human epithelial colorectal cell culture on PDMS substrates, the inclusion of biomimetic topographical features enhanced alkaline phosphatase expression 2.3-fold compared to flat controls, suggesting biomimetic topography is important in induced epithelial differentiation. This work presents a facile, inexpensive method for precisely replicating complex hierarchal features of native tissue, towards a new model for regenerative medicine and drug delivery for intestinal disorders and diseases. PMID- 27550931 TI - Vitamin D and Lung Infection. AB - Available data suggest that vitamin D plays a role in controlling inflammation in the lungs. However, to date vitamin D-induced production of cathelicidin has not been shown to have an effect on the burden of either viruses or bacteria. Future work should continue to determine the effects of vitamin D-regulated mechanisms in the lung and the possible role of cathelicidin against different pulmonary pathogens in vivo. PMID- 27550932 TI - Gene bb0318 Is Critical for the Oxidative Stress Response and Infectivity of Borrelia burgdorferi. AB - A greater understanding of the molecular mechanisms that Borrelia burgdorferi uses to survive during mammalian infection is critical for the development of novel diagnostic and therapeutic tools to improve the clinical management of Lyme disease. By use of an in vivo expression technology (IVET)-based approach to identify B. burgdorferi genes expressed in vivo, we discovered the bb0318 gene, which is thought to encode the ATPase component of a putative riboflavin ABC transport system. Riboflavin is a critical metabolite enabling all organisms to maintain redox homeostasis. B. burgdorferi appears to lack the metabolic capacity for de novo synthesis of riboflavin and so likely relies on scavenging riboflavin from the host environment. In this study, we sought to investigate the role of bb0318 in B. burgdorferi pathogenesis. No in vitro growth defect was observed for the Deltabb0318 clone. However, the mutant spirochetes displayed reduced levels of survival when exposed to exogenous hydrogen peroxide or murine macrophages. Spirochetes lacking bb0318 were found to have a 100-fold-higher 50% infectious dose than spirochetes containing bb0318 In addition, at a high inoculum dose, bb0318 was found to be important for effective spirochete dissemination to deep tissues for as long as 3 weeks postinoculation and to be critical for B. burgdorferi infection of mouse hearts. Together, these data implicate bb0318 in the oxidative stress response of B. burgdorferi and indicate the contribution of bb0318 to B. burgdorferi mammalian infectivity. PMID- 27550933 TI - Polysaccharide Capsule Composition of Pneumococcal Serotype 19A Subtypes Is Unaltered among Subtypes and Independent of the Nutritional Environment. AB - Serotype 19A strains have emerged as a cause of invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), and serotype 19A has now been included in the recent 13-valent vaccine (PCV13). Genetic analysis has revealed at least three different capsular serotype 19A subtypes, and nutritional environment-dependent variation of the 19A capsule structure has been reported. Pneumococcal vaccine effectiveness and serotyping accuracy might be impaired by structural differences in serotype 19A capsules. We therefore analyzed the distribution of 19A subtypes collected within a Swiss national surveillance program and determined capsule composition under different nutritional conditions with high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. After the introduction of PCV7, a significant relative increase of subtype 19A-II and decrease of 19A-I occurred. Chemical analyses showed no difference in the composition as well as the linkage of 19A subtype capsular saccharides grown in defined and undefined growth media, which is consistent with a trisaccharide repeat unit composed of rhamnose, N-acetyl-mannosamine, and glucose. In summary, our study suggests that no structural variance dependent of the nutritional environment or the subtype exists. The serotype 19A subtype shift observed after the introduction of the PCV7 can therefore not be explained by selection of a capsule structure variant. However, capsule composition analysis of emerging 19A clones is recommended in cases where there is no other explanation for a selective advantage, such as antibiotic resistance or loss or acquisition of other virulence factors. PMID- 27550934 TI - Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes. AB - Vibrio cholerae is an intestinal pathogen that causes the diarrheal disease cholera. Colonization of the intestine depends upon the expression of genes that allow V. cholerae to overcome host barriers, including low pH, bile acids, and the innate immune system. ToxR is a major contributor to this process. ToxR is a membrane-spanning transcription factor that coordinates gene expression in response to environmental cues. In previous work we showed that ToxR upregulated leuO expression in response to bile salts. LeuO is a LysR family transcription factor that contributes to acid tolerance, bile resistance, and biofilm formation in V. cholerae Here, we investigated the function of ToxR and LeuO in cationic antimicrobial peptide (CAMP) resistance. We report that ToxR and LeuO contribute to CAMP resistance by regulating carRS transcription. CarRS is a two-component regulatory system that positively regulates almEFG expression. AlmEFG confers CAMP resistance by glycinylation of lipid A. We found that the expression of carRS and almEFG and the polymyxin B MIC increased in mutants lacking toxRS or leuO Conversely, leuO overexpression decreased the polymyxin B MIC. Furthermore, we found that LeuO directly bound to the carRS promoter and that ToxR-dependent activation of leuO transcription regulated carRS transcription in response to bile salts. Our results suggest that LeuO functions downstream of ToxR to modulate carRS expression in response to environmental cues. This study extends the functional role of ToxR and LeuO in environmental adaptation to include cell surface remodeling and CAMP resistance. PMID- 27550940 TI - Identification of Pharmacodynamic Transcript Biomarkers in Response to FGFR Inhibition by AZD4547. AB - The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines. Consistent with known signaling pathways activated by FGFR, we identified transcript biomarkers downstream of the RAS-MAPK and PI3K/AKT pathways. Using different tumor cell lines in vitro and xenografts in vivo, we confirmed that some of these transcript biomarkers (DUSP6, ETV5, YPEL2) were modulated downstream of oncogenic FGFR1, 2, 3, whereas others showed selective modulation only by FGFR2 signaling (EGR1). These transcripts showed consistent time-dependent modulation, corresponding to the plasma exposure of AZD4547 and inhibition of phosphorylation of the downstream signaling molecules FRS2 or ERK. Combination of FGFR and AKT inhibition in an FGFR2-mutated endometrial cancer xenograft model enhanced modulation of transcript biomarkers from the PI3K/AKT pathway and tumor growth inhibition. These biomarkers were detected on the clinically validated nanoString platform. Taken together, these data identified novel dynamic transcript biomarkers of FGFR inhibition that were validated in a number of in vivo models, and which are more robustly modulated by FGFR inhibition than some conventional downstream signaling protein biomarkers. Mol Cancer Ther; 15(11); 2802-13. (c)2016 AACR. PMID- 27550935 TI - Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain. AB - Yersinia enterocolitica evades the immune response by injecting Yersinia outer proteins (Yops) into the cytosol of host cells. YopH is a tyrosine phosphatase critical for Yersinia virulence. However, the mucosal immune mechanisms subverted by YopH during in vivo orogastric infection with Y. enterocolitica remain elusive. The results of this study revealed neutrophil recruitment to Peyer's patches (PP) after infection with a YopH-deficient mutant strain (Y. enterocolitica DeltayopH). While the Y. enterocolitica wild-type (WT) strain in PP induced the major neutrophil chemoattractant CXCL1 mRNA and protein levels, infection with the Y. enterocolitica DeltayopH mutant strain exhibited a higher expression of the CXCL1 receptor, CXCR2, in blood neutrophils, leading to efficient neutrophil recruitment to the PP. In contrast, migration of neutrophils into PP was impaired upon infection with Y. enterocolitica WT strain. In vitro infection of blood neutrophils revealed the involvement of YopH in CXCR2 expression. Depletion of neutrophils during Y. enterocolitica DeltayopH infection raised the bacterial load in PP. Moreover, the clearance of WT Y. enterocolitica was improved when an equal mixture of Y. enterocolitica WT and Y. enterocolitica DeltayopH strains was used in infecting the mice. This study indicates that Y. enterocolitica prevents early neutrophil recruitment in the intestine and that the effector protein YopH plays an important role in the immune evasion mechanism. The findings highlight the potential use of the Y. enterocolitica YopH deficient strain as an oral vaccine carrier. PMID- 27550942 TI - TLR4-Dependent Claudin-1 Internalization and Secretagogue-Mediated Chloride Secretion Regulate Irinotecan-Induced Diarrhea. AB - We have previously shown increased intestinal permeability, to 4-kDa FITC dextran, in BALB/c mice treated with irinotecan. Importantly, genetic deletion of Toll-like receptor 4 (TLR4; Tlr4-/-) protected against loss of barrier function, indicating that TLR4 is critical in tight junction regulation. The current study aimed (i) to determine the molecular characteristics of intestinal tight junctions in wild-type and Tlr4-/- BALB/c mice and (ii) to characterize the secretory profile of the distal colon. Forty-two female wild-type and 42 Tlr4-/- BALB/c mice weighing between 18 and 25 g received a single 270 mg/kg [intraperitoneal (i.p.)] dose of irinotecan hydrochloride or vehicle control and were killed at 6, 24, 48, 72, and 96 hours. The secretory profile of the distal colon, following carbachol and forksolin, was assessed using Ussing chambers at all time points. Tight junction integrity was assessed at 24 hours, when peak intestinal permeability and diarrhea were reported, using immunofluorescence, Western blotting, and RT-PCR. Irinotecan caused internalization of claudin-1 with focal lesions of ZO-1 and occludin proteolysis in the ileum and colon of wild type mice. Tlr4-/- mice maintained phenotypically normal tight junctions. Baseline conductance, a measure of paracellular permeability, was increased in irinotecan-treated wild-type mice at 24 hours (53.19 +/- 6.46 S/cm2; P = 0.0008). No change was seen in Tlr4-/- mice. Increased carbachol-induced chloride secretion was seen in irinotecan-treated wild-type and Tlr4-/- mice at 24 hours (wild-type: 100.35 +/- 18.37 MUA/cm2; P = 0.022; Tlr4-/-: 102.72 +/- 18.80 MUA/cm2; P = 0.023). Results suggest that TLR4-dependent claudin-1 internalization and secondary anion secretion contribute to irinotecan-induced diarrhea. Mol Cancer Ther; 15(11); 2767-79. (c)2016 AACR. PMID- 27550943 TI - A Novel Polyphenol Conjugate Sensitizes Cisplatin-Resistant Head and Neck Cancer Cells to Cisplatin via Nrf2 Inhibition. AB - Many cancer cells show acquired resistance to chemotherapeutic agents, such as cisplatin. This is a major cause of cancer treatment failure, and novel agents to overcome resistance are thus urgently required. A novel synthetic polyphenol conjugate, (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP 23), selectively kills tumor cells via the reactive oxygen species (ROS)-mediated unfolded protein response. We investigated the ability of DPP-23 to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Cisplatin-resistant HNC cell lines and their parental and other HNC cell lines were used. The effects of cisplatin and DPP-23 were assessed alone and in combination in HNC and normal cells using cell viability, cell cycle, and cell death assays, by measuring glutathione (GSH), ROS, and protein levels, and via preclinical mouse studies. DPP-23 induced selective cell death in HNC cells, including cisplatin-resistant HNC cells, but spared normal cells, via cellular GSH depletion and ROS accumulation. The effect was blocked by the antioxidant N-acetyl-L-cysteine. DPP-23 activated p53 and its related cell death pathways via a robust accumulation of cellular ROS that involved inhibition of nuclear factor erythroid 2-related factor 2 antioxidant defense mechanisms. Thus, DPP-23 significantly overcame cisplatin resistance in HNC cells in vitro and in vivo As a promising anticancer strategy, ROS generation and subsequent selective cancer cell killing by DPP-23 might help to overcome cisplatin resistance in HNC. Mol Cancer Ther; 15(11); 2620-9. (c)2016 AACR. PMID- 27550941 TI - Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2. AB - Despite advances in targeted therapy, lung cancer remains the most common cause of cancer-related mortality in the United States. Chromosomal instability is a prominent feature in lung cancer and, because it rarely occurs in normal cells, it represents a potential therapeutic target. Our prior work discovered that lung cancer cells undergo anaphase catastrophe in response to inhibition of cyclin dependent kinase 2 (CDK2), followed by apoptosis and reduced growth. In this study, the effects and mechanisms of the multi-CDK inhibitor dinaciclib on lung cancer cells were investigated. We sought to determine the specificity of CDK dependent induction of anaphase catastrophe. Live cell imaging provided direct evidence that dinaciclib caused multipolar cell divisions resulting in extensive chromosome missegregation. Genetic knockdown of dinaciclib CDK targets revealed that repression of CDK2 and CDK1, but not CDK5 or CDK9, triggered anaphase catastrophe in lung cancer cells. Overexpression of CP110, which is a mediator of CDK2 inhibitor-induced anaphase catastrophe (and a CDK1 and 2 phosphorylation substrate), antagonized anaphase catastrophe and apoptosis following dinaciclib treatment. Consistent with our previous findings, acquisition of activated KRAS sensitized lung cancer cells to dinaciclib-mediated anaphase catastrophe and cell death. Combining dinaciclib with the mitotic inhibitor taxol augmented anaphase catastrophe induction and reduced cell viability of lung cancer cells. Thus, the multi-CDK inhibitor dinaciclib causes anaphase catastrophe in lung cancer cells and should be investigated as a potential therapeutic for wild-type and KRAS mutant lung cancer, individually or in combination with taxanes. Mol Cancer Ther; 15(11); 2758-66. (c)2016 AACR. PMID- 27550944 TI - The Discovery and Preclinical Development of ASG-5ME, an Antibody-Drug Conjugate Targeting SLC44A4-Positive Epithelial Tumors Including Pancreatic and Prostate Cancer. AB - Here, we report the development of an antibody-drug conjugate, ASG-5ME, which targets the solute carrier receptor SLC44A4. SLC44A4 is a member of a family of putative choline transporters that we show to be markedly upregulated in a variety of epithelial tumors, most notably prostate and pancreatic cancer. SLC44A4 is normally expressed on the apical surface of secretory epithelial cells, but in cancer we show expression is not restricted to the luminal surface in advanced and undifferentiated tumors. ASG-5ME consists of a human IgG2 anti SLC44A4 antibody conjugated through a cleavable linker to the microtubule disrupting agent monomethylauristatin E. It has potent antitumor activity in both cell line - and patient-derived xenograft models of pancreatic and prostate cancers. Combination studies with ASG-5ME and nab-paclitaxel demonstrated combination effect in both pancreatic and prostate tumor models. Altogether, the data presented here suggest that ASG-5ME may have the potential to offer a new therapeutic option for the treatment of pancreatic and prostate cancers. Mol Cancer Ther; 15(11); 2679-87. (c)2016 AACR. PMID- 27550945 TI - Differences in time-dependent mechanical properties between extruded and molded hydrogels. AB - The mechanical properties of hydrogels used in biomaterials and tissue engineering applications are critical determinants of their functionality. Despite the recent rise of additive manufacturing, and specifically extrusion based bioprinting, as a prominent biofabrication method, comprehensive studies investigating the mechanical behavior of extruded constructs remain lacking. To address this gap in knowledge, we compared the mechanical properties and swelling properties of crosslinked gelatin-based hydrogels prepared by conventional molding techniques or by 3D bioprinting using a BioBots Beta pneumatic extruder. A preliminary characterization of the impact of bioprinting parameters on construct properties revealed that both Young's modulus and optimal extruding pressure increased with polymer content, and that printing resolution increased with both printing speed and nozzle gauge. High viability (>95%) of encapsulated NIH 3T3 fibroblasts confirmed the cytocompatibility of the construct preparation process. Interestingly, the Young's moduli of extruded and molded constructs were not different, but extruded constructs did show increases in both the rate and extent of time-dependent mechanical behavior observed in creep. Despite similar polymer densities, extruded hydrogels showed greater swelling over time compared to molded hydrogels, suggesting that differences in creep behavior derived from differences in microstructure and fluid flow. Because of the crucial roles of time-dependent mechanical properties, fluid flow, and swelling properties on tissue and cell behavior, these findings highlight the need for greater consideration of the effects of the extrusion process on hydrogel properties. PMID- 27550946 TI - Three-dimensional bioprinting of cell-laden constructs with polycaprolactone protective layers for using various thermoplastic polymers. AB - Three-dimensional (3D) cell-printed constructs have been recognized as promising biological substitutes for tissue/organ regeneration. They provide tailored physical properties and biological cues via multi-material printing process. In particular, hybrid bioprinting, enabling to use biodegradable synthetic polymers as framework, has been an attractive method to support weak hydrogels. The constructs with controlled architecture and high shape fidelity were fabricated through this method, depositing spatial arrangement of multi-cell types into microscale constructs. Among biodegradable synthetic polymers, polycaprolactone (PCL) has been commonly chosen in fabrication of cell-printed constructs because of its low melting temperature of 60 degrees C to be dispensed with extrusion based bioprinting system. However, in addition to PCL, various synthetic polymers have been widely applied for tissue regeneration. These polymers have distinctive characteristics essential for tissue/organ regeneration. Nevertheless, it is difficult to use some polymers, such as poly (lactic-co-glycolic acid) (PLGA) and polylactic acid (PLA) with 3D bioprinting technology because of their high melting temperature to be dispensed, which can result in thermal damage to the cells in the printed constructs during the fabrication process. We present a novel bioprinting method to use various synthetic polymers in fabrication of cell printed constructs. PCL was introduced as a protective layer to prevent thermal damage caused by high temperature of polymers during fabrication. Remarkable improvement in cellular activities in the printed constructs with PCL layers was observed compared with the construct without PCL. This bioprinting method can be applied to fabricate more tissue-like constructs through the use of various biomaterials. PMID- 27550948 TI - Knowledge, Attitude and Practice Survey of Prescribing Opioids for Chronic Noncancer Pain in Taiwan-Comparison of Pain and Non-Pain Physicians. AB - BACKGROUND: Prescribing opioids for chronic noncancer pain (CNCP) has been strictly regulated in Taiwan. This study was undertaken to survey pain and non pain related physicians' knowledge, attitudes, and practices regarding prescribing opioids for CNCP. METHODS: A questionnaire survey was conducted in this comparison study. All 66 physicians who were treating officially registered CNCP outpatients were visited and completed anonymous questionnaires. The other physicians (anesthesiologists, oncologists, and non-pain physicians) were surveyed by a mailed questionnaire. RESULTS: A total of 266 (75%) questionnaires were received from 355 board-certified physicians. More CNCP physicians (81.8%) and anesthesiologists (69.7%) had received prior CNCP-related training courses than had oncologists (21.2%) and non-pain physicians (10.3%). Varied proportions of physicians by type were unfamiliar with the Taiwan opioid regulations (16.7 86.8%) and would accordingly skip or reduce dosage of opioid prescriptions (27.3 73.5%). In addition, non-pain physicians had a significantly lower knowledge level, more negative attitudes, and greater hesitation about prescribing opioids compared to the pain-related physicians (P < 0.001). CNCP physicians who had received CNCP-related training courses had a higher knowledge score than did those not receiving training (P = 0.002). Overall, the leading barriers for prescribing opioids were inadequate knowledge of pain management (76%), physician reluctance (73%), and family reluctance (78%). CONCLUSION: There are substantial knowledge gaps, negative attitudes, and hesitation toward prescribing long-term opioids for CNCP patients by physicians in Taiwan, suggesting that efforts are needed to improve postgraduate education regarding adequate opioid management for CNCP. PMID- 27550947 TI - A design concept of parallel elasticity extracted from biological muscles for engineered actuators. AB - Series elastic actuation that takes inspiration from biological muscle-tendon units has been extensively studied and used to address the challenges (e.g. energy efficiency, robustness) existing in purely stiff robots. However, there also exists another form of passive property in biological actuation, parallel elasticity within muscles themselves, and our knowledge of it is limited: for example, there is still no general design strategy for the elasticity profile. When we look at nature, on the other hand, there seems a universal agreement in biological systems: experimental evidence has suggested that a concave-upward elasticity behaviour is exhibited within the muscles of animals. Seeking to draw possible design clues for elasticity in parallel with actuators, we use a simplified joint model to investigate the mechanisms behind this biologically universal preference of muscles. Actuation of the model is identified from general biological joints and further reduced with a specific focus on muscle elasticity aspects, for the sake of easy implementation. By examining various elasticity scenarios, one without elasticity and three with elasticity of different profiles, we find that parallel elasticity generally exerts contradictory influences on energy efficiency and disturbance rejection, due to the mechanical impedance shift thus caused. The trade-off analysis between them also reveals that concave parallel elasticity is able to achieve a more advantageous balance than linear and convex ones. It is expected that the results could contribute to our further understanding of muscle elasticity and provide a theoretical guideline on how to properly design parallel elasticity behaviours for engineering systems such as artificial actuators and robotic joints. PMID- 27550949 TI - An Evidence-Based Review of the Efficacy of Perioperative Analgesic Techniques for Breast Cancer-Related Surgery. AB - Objective: To review the published evidence regarding perioperative analgesic techniques for breast cancer-related surgery. Design: Topical review. Methods: Randomized, controlled trials (RCTs) were selected for inclusion in the review. Also included were large prospective series providing estimates of potential risks and technical reports and small case series demonstrating a new technique or approaches of interest to clinicians. Results: A total of 514 abstracts were reviewed, with 284 studies meeting criteria for full review. The evidence regarding preemptive ketamine, scheduled opioids, perioperative non-steroidal anti-inflammatory drugs (NSAIDs), and intravenous lidocaine is mixed and deserves further investigation. There is strong evidence that both pregabalin and gabapentin provide analgesic benefits following breast surgery. There is minimal and conflicting data from high-quality randomized, controlled studies suggesting that directly infiltrating and/or infusing local anesthetic (liposome encapsulated or unencapsulated) into the surgical wound is a reliably effective analgesic. In contrast, there is a plethora of data demonstrating the potent analgesia, opioid sparing, and decreased opioid-related side effects from thoracic epidural infusion and both single-injection and continuous paravertebral nerve blocks (the latter two demonstrating decreased persistent post-surgical pain between 2.5 and 12 months). Techniques with limited-yet promising-data deserving additional investigation include brachial plexus blocks, cervical epidural infusion, interfascial plane blocks, and interpleural blocks. Conclusions: While there are currently multiple promising analgesic techniques for surgical procedures of the breast that deserve further study, the only modalities demonstrated to provide potent, consistent perioperative pain control are thoracic epidural infusion and paravertebral nerve blocks. PMID- 27550951 TI - Surgical Site Infections in Cancer Patients with Intrathecal Drug Delivery Devices. AB - Objectives: Our purpose was to determine the incidence of surgical site infection (SSI) in cancer patients receiving an intrathecal drug delivery system (IDDS) and compare that rate with the incidence of SSI in the general population receiving an IDDS or spinal cord stimulator. We attempted to describe risk factors for SSIs in cancer patients treated with IDDS in terms of exposure to cancer treatments. Design: Retrospective review. Setting: Large tertiary care center. Patients: Cancer patients receiving an IDDS in 2006-2013. Methods: The incidence of SSI was determined according to the US Centers for Disease Control and Prevention definition. Medication regimens and current cancer treatment were investigated to identify immunocompromised patients during IDDS placement. Microbacteriology, treatment, and overall outcomes were investigated. Results: Sixty-four patients had an IDDS implanted in 2006-2013. SSI developed in four patients (6.2%). All four patients had received chemotherapy or radiotherapy within three months before implantation. Three of the three were receiving dexamethasone, and three of the four required explantation of the IDDS. Conclusion: The incidence of SSI was at the upper end of the published infection rates for IDDS. The risk of SSI may be increased in this population because of factors that alter the patient's immune status, including concomitant corticosteroid use, radiotherapy near the SSI, and presence of immunomodulators. The identification and mitigation of certain risk factors for this population may prevent infection in future patients. PMID- 27550952 TI - Dexamethasone and Clonidine, but not Epinephrine, Prolong Duration of Ropivacaine Brachial Plexus Blocks, Cross-Sectional Analysis in Outpatient Surgery Setting. AB - Objective: The primary aim of this study is to determine the effect of adding dexamethasone, clonidine or both with and without epinephrine to ropivacaine and bupivacaine brachial plexus blocks. Design: Observational study of prospectively collected data. Setting: Single academic outpatient surgery center. Methods: We evaluated 5,515 patient entries who received brachial plexus block (BPB). Multiple, rescue, unsuccessful, and distal nerve blocks of the upper extremity were excluded. The duration was calculated from the time the block was performed until the resolution of the block by patient report. Block durations were compared using Analysis of Variance. Results: After exclusions, 3,706 nerve blocks were analyzed. The median concentration of ropivacaine used was 0.5%. Both clonidine and dexamethasone significantly increased block duration by 1.1 and 3.0 hours, respectively. Combining clonidine and dexamethasone with ropivacaine increased block duration by 6.2 hours (p<0.001) when compared to ropivacaine alone. Dexamethasone and Clonidine increased block duration by 5.2 hours (p<0.001) when compared to clonidine alone and by 3.2 hours (p<0.001) compared to dexamethasone alone. The addition of epinephrine to any of the adjuvants made no statistically significant difference to the duration of action except when it was added to dexamethasone. Summary: For brachial plexus blocks, epinephrine did not affect the duration of analgesia when added to ropivacaine. Epinephrine did not enhance the observed increase of block duration induced by clonidine or the combination of clonidine and dexamethasone. The most block duration enhancement was observed when combination of clonidine and dexamethasone were added to ropivacaine. PMID- 27550953 TI - A Phase II Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Lenalidomide in Lumbar Radicular Pain with a Long-Term Open-Label Extension Phase. AB - Objective: This phase II study assessed lenalidomide efficacy and safety. Design: Three-phase core study: 14-day prerandomization, 12-week treatment, and 52-week open-label extension. Setting: Fourteen US centers from July 2005 to July 2007. Subjects: Chronic lumbar radicular pain patients without history of nerve injury or deficit. Methods: Subjects were randomized (1:1) to double-blind treatment with lenalidomide 10 mg or placebo once daily for 12 weeks, followed by a 52-week open-label extension. A 12-week, single-center, randomized-withdrawal (1:2, lenalidomide:placebo), exploratory study with open-label extension was undertaken in 12 subjects from the core extension who were naive to neuropathic medications and with at least a two-point decrease from baseline average daily Pain Intensity Numerical Rating Scale score. Results: Of 180 subjects enrolled, 176 had at least one postbaseline measure; 132 completed the 12-week treatment phase. In the core study, no statistically significant difference in Pain Intensity-Numerical Rating Scale mean change (-0.02, P = 0.958) was observed at week 12 between lenalidomide and placebo; proportions achieving pain reduction at week 12 and other secondary measures were comparable between lenalidomide and placebo. In the exploratory study, week 12 mean changes in Pain Intensity-Numerical Rating Scale scores were -0.05 (lenalidomide: N = 3) and 2.11 (placebo: N = 8). Mean changes in Brief Pain Inventory-short form interference scores were -3.33 and 8.38, respectively; scores at six months were maintained or decreased in 10 of 12 subjects. Conclusions: While this study does not support lenalidomide use in an unselected lumbar radicular pain population, an immunomodulating agent may relieve pain in select subjects naive to neuropathic pain medications. : ClinicalTrials.gov identifier: NCT00120120. PMID- 27550956 TI - Radiofrequency Electrode Failure During a Percutaneous Cervical Cordotomy: Standard Testing Software Algorithms of Modern RF Machines May Fail to Detect Faults. PMID- 27550954 TI - Abuse Potential Study of ALO-02 (Extended-Release Oxycodone Surrounding Sequestered Naltrexone) Compared with Immediate-Release Oxycodone Administered Orally to Nondependent Recreational Opioid Users. AB - Objective: To evaluate the abuse potential of ALO-02, an abuse-deterrent formulation comprising pellets of extended-release oxycodone hydrochloride surrounding sequestered naltrexone hydrochloride. Design: Randomized, double blind, placebo-/active-controlled, 6-way crossover study, with naloxone challenge, drug discrimination, and treatment phases. Subjects: Nondependent, recreational opioid users. Methods: Oral administration of crushed and intact ALO 02, crushed immediate-release (IR) oxycodone, and placebo. Primary endpoints were Drug Liking and High measured on visual analog scales and reported as maximum effect (E max ) and area-under-the-effect-curve from 0 to 2 hours (AUE 0-2h ). Other pharmacodynamic, pharmacokinetic and safety assessments were included. Results: Drug Liking and High (E max ) for crushed oxycodone IR 40 mg were significantly higher compared with placebo, confirming study validity ( P < 0.0001). Drug Liking and High (E max, AUE 0-2h ) for crushed ALO-02 (40 mg/4.8 mg and 60 mg/7.2 mg) were significantly lower compared to corresponding doses of crushed oxycodone IR (40 and 60 mg; P < 0.0001). Likewise, Drug Liking and High (E max and AUE 0-2h ) for intact ALO-02 60 mg/7.2 mg were significantly lower compared with crushed oxycodone IR 60 mg ( P < 0.0001). Secondary pharmacodynamic endpoints and plasma concentrations of oxycodone and naltrexone were consistent with these results. Fewer participants experienced adverse events (AEs) after ALO-02 (crushed or intact: 71.1-91.9%) compared with crushed oxycodone IR (100%). Most common AEs following crushed ALO-02 and oxycodone IR were euphoric mood, pruritus, somnolence, and dizziness. Conclusions: The results suggest that ALO-02 (crushed or intact) has lower abuse potential than crushed oxycodone IR when administered orally in nondependent, recreational opioid users. PMID- 27550957 TI - Response to Letter by Hamilton et al. PMID- 27550958 TI - Improved Outcomes Associated with the Liberal Use of Thoracic Epidural Analgesia in Patients with Rib Fractures. AB - Objective: Each year, more than 150,000 patients with rib fractures are admitted to US trauma centers; as many as 10% die. Effective pain control is critical to survival. One way to manage pain is thoracic epidural analgesia. If this treatment reduces mortality, more frequent use may be indicated. Methods: We analyzed the patient registry of a level II trauma center. All patients admitted with one or more rib fractures (N = 1,347) were considered. Patients who were not candidates for epidural analgesia (N = 382) were eliminated. Mortality was assessed with binary logistic regressions. Results: Across the total population, mortality was 6.7%; incidence of pneumonia was 11.1%; mechanical ventilation was required in 23.8% of patients, for an average duration of 10.0 days; average stay in the hospital was 7.7 nights; and 49.7% of patients were admitted to the ICU for an average of 7.2 nights. Epidural analgesia was administered to 18.4% of patients. After matching samples for candidacy, patients who received epidurals were 3.7 years older, fractured 2.6 more ribs, had higher injury severity scores, and were more likely to present with bilateral fractures, flail segments, pulmonary contusions, hemothoraces, and pneumothoraces. Despite greater injury severity, mortality among these patients was lower (0.5%) than those who received alternative care (1.9%). Controlling for age, injury severity, and use of mechanical ventilation, epidural analgesia predicted a 97% reduction in mortality. Conclusion: Thoracic epidural analgesia associates with reduced mortality in rib fracture patients. Better care of this population is likely to be facilitated by more frequent reliance on this treatment. PMID- 27550959 TI - Effects of Testosterone Replacement on Pain Catastrophizing and Sleep Quality in Men with Opioid-Induced Androgen Deficiency. AB - Objective: The objective of this investigation was to determine the effects of testosterone administration on pain catastrophizing and sleep quality in adult men with opioid-induced androgen deficiency. Design: Sixty-two men aged 18-64 years using opioid analgesics for chronic non-cancer pain with total testosterone levels < 350 ng/dl were randomized to 14 weeks of transdermal testosterone gel or placebo gel daily. Total testosterone levels were measured by liquid chromatography mass spectrometry and free testosterone was calculated using the law of mass action equation. Outcomes were assessed by administering validated instruments such as Pain Catastrophizing Scale (PCS) and Insomnia Severity Index (ISI) at baseline and 14 weeks. Results: Baseline characteristics were similar between the two groups. Mean (SD) total testosterone concentrations increased from 223 +/- 86 to 775 +/- 555 ng/dl in the testosterone group, but did not meaningfully change in placebo group. Mean changes in PCS and ISI scores during intervention did not differ significantly between groups and were not related to changes in on-treatment serum testosterone concentrations. Conclusion: In this 14 week trial, testosterone administration in men with opioid-induced androgen deficiency was not associated with improvements in pain catastrophizing or sleep quality. PMID- 27550960 TI - Tunneling nanotubes spread fibrillar alpha-synuclein by intercellular trafficking of lysosomes. AB - Synucleinopathies such as Parkinson's disease are characterized by the pathological deposition of misfolded alpha-synuclein aggregates into inclusions throughout the central and peripheral nervous system. Mounting evidence suggests that intercellular propagation of alpha-synuclein aggregates may contribute to the neuropathology; however, the mechanism by which spread occurs is not fully understood. By using quantitative fluorescence microscopy with co-cultured neurons, here we show that alpha-synuclein fibrils efficiently transfer from donor to acceptor cells through tunneling nanotubes (TNTs) inside lysosomal vesicles. Following transfer through TNTs, alpha-synuclein fibrils are able to seed soluble alpha-synuclein aggregation in the cytosol of acceptor cells. We propose that donor cells overloaded with alpha-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. Our findings thus reveal a possible novel role of TNTs and lysosomes in the progression of synucleinopathies. PMID- 27550961 TI - Preclinical progress and first translational steps for a liposomal chemotherapy protocol against adrenocortical carcinoma. AB - Systemic therapy of adrenocortical carcinoma (ACC) is limited by heterogeneous tumor response and adverse effects. Recently, we demonstrated anti-tumor activity of LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin, mitotane), a liposomal variant of EDP-M (etoposide, doxorubicin, cisplatin, mitotane). To improve the therapeutic efficacy and off-target profiles of the clinical gold standard EDP-M, we investigated liposomal EDP-M regimens in different preclinical settings and in a small number of ACC patients with very advanced disease. Short- and long-term experiments were performed on two ACC models (SW-13 and SJ-ACC3) in vivo We evaluated the anti-tumoral effects and off-target profiles of EDP-M, LEDP M and a novel regimen L(l)EDP-M including liposomal etoposide. Furthermore, the role of plasma microRNA-210 as a therapeutic biomarker and first clinical data were assessed. Classical and liposomal protocols revealed anti-proliferative efficacy against SW-13 (EDP-M P < 0.01; LEDP-M: P < 0.001; L(l)EDP-M: P < 0.001 vs controls), whereas in SJ-ACC3, only EDP-M (P < 0.05 vs controls) was slightly effective. Long-term experiments in SW-13 demonstrated anti-tumor efficacy for all treatment schemes (EDP-M: P < 0.01, LEDP-M: P < 0.05, L(l)EDP-M P < 0.001 vs controls). The analysis of pre-defined criteria leading to study termination revealed significant differences for control (P < 0.0001) and EDP-M (P = 0.003) compared to L(l)EDP-M treatment. Raising its potential for therapy monitoring, we detected elevated levels of circulating microRNA-210 in SW-13 after LEDP-M treatment (P < 0.05). In contrast, no comparable effects were detectable for SJ ACC3. However, overall histological evaluation demonstrated improved off-target profiles following liposomal regimens. The first clinical data indicate improved tolerability of liposomal EDP-M, thus confirming our results. In summary, liposomal EDP-M regimens represent promising treatment options to improve clinical treatment of ACC. PMID- 27550963 TI - Defects in homologous recombination repair behind the human diseases: FA and HBOC. AB - Hereditary breast and ovarian cancer (HBOC) syndrome and a rare childhood disorder Fanconi anemia (FA) are caused by homologous recombination (HR) defects, and some of the causative genes overlap. Recent studies in this field have led to the exciting development of PARP inhibitors as novel cancer therapeutics and have clarified important mechanisms underlying genome instability and tumor suppression in HR-defective disorders. In this review, we provide an overview of the basic molecular mechanisms governing HR and DNA crosslink repair, highlighting BRCA2, and the intriguing relationship between HBOC and FA. PMID- 27550962 TI - Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk. AB - Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight. PMID- 27550964 TI - GPR41 modulates insulin secretion and gene expression in pancreatic beta-cells and modifies metabolic homeostasis in fed and fasting states. AB - Insulin secretion by pancreatic beta-cells is primarily regulated by glucose; however, hormones and additional nutrients, such as long-chain fatty acids, also play an important role in adjusting insulin output to physiologic needs. To examine the role of short-chain fatty acids (SCFAs) in beta-cell function, we analyzed mouse models of gain and loss of function of GPR41 (FFAR3), a receptor for SCFAs, vs. wild-type control mice. GPR41 gain of function [GPR41 overexpressing transgenic (41 Tg) model] and GPR41 loss of function [GPR41 knockout (KO 41) model] resulted in complementary changes in glucose tolerance, without significant effects on insulin sensitivity. KO 41 mice showed fasting hypoglycemia, which was consistent with increased basal and glucose-induced insulin secretion by islets in vitro Mirroring this, 41 Tg islets showed impaired glucose responsiveness in vitro Microarray analysis of islets from 41 Tg mice indicated significant alterations in gene expression patterns; several of the altered genes were chosen for further analysis and were also observed to change upon incubation of islets?? and cultured beta-cells with SCFAs in a GPR41 dependent manner. Taken together, our results indicate that GPR41 and its ligands, SCFAs, may play an important role in the fine-tuning of insulin secretion in fed and fasting states.-Veprik, A., Laufer, D., Weiss, S., Rubins, N., Walker, M. D. GPR41 modulates insulin secretion and gene expression in pancreatic beta-cells and modifies metabolic homeostasis in fed and fasting states. PMID- 27550966 TI - Randomized Trials to Evaluate Cardiovascular Safety of Antihyperglycemic Medications: A Worthwhile Effort? PMID- 27550965 TI - Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle. AB - Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2 methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 MUM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle. PMID- 27550967 TI - Cardioprotection: The Disconnect Between Bench and Bedside. PMID- 27550969 TI - Original Surgical Procedure for the Treatment of Protein-Losing Enteropathy in Fontan Patients: Report of Two Midterm Successes. PMID- 27550970 TI - Letter by Littmann Regarding Article, "Giant J Waves and ST-Segment Elevation Associated With Acute Gastric Distension". PMID- 27550971 TI - Response by Sharkey et al to Letter Regarding Article, "Giant J Waves and ST Segment Elevation Associated With Acute Gastric Distension". PMID- 27550968 TI - Trajectories of Cardiovascular Risk Factors and Incidence of Atrial Fibrillation Over a 25-Year Follow-Up: The ARIC Study (Atherosclerosis Risk in Communities). AB - BACKGROUND: Timing and trajectories of cardiovascular risk factor (CVRF) development in relation to atrial fibrillation (AF) have not been described previously. We assessed trajectories of CVRF and incidence of AF over 25 years in the ARIC study (Atherosclerosis Risk in Communities). METHODS: We assessed trajectories of CVRF in 2456 individuals with incident AF and 6414 matched control subjects. Subsequently, we determined the association of CVRF trajectories with the incidence of AF among 10 559 AF-free individuals (mean age, 67 years; 52% men; 20% blacks). Risk factors were measured during 5 examinations between 1987 and 2013. Cardiovascular events, including incident AF, were ascertained continuously. We modeled the prevalence of risk factors and cardiovascular outcomes in the period before and after AF diagnosis and the corresponding index date for control subjects using generalized estimating equations. Trajectories in risk factors were identified with latent mixture modeling. The risk of incident AF by trajectory group was examined with Cox models. RESULTS: The prevalence of stroke, myocardial infarction, and heart failure increased steeply during the time close to AF diagnosis. All CVRFs were elevated in AF cases compared with controls >15 years before diagnosis. We identified distinct trajectories for all the assessed CVRFs. In general, individuals with trajectories denoting long-term exposure to CVRFs had increased AF risk even after adjustment for single measurements of the CVRFs. CONCLUSIONS: AF patients have increased prevalence of CVRF many years before disease diagnosis. This analysis identified diverse trajectories in the prevalence of these risk factors, highlighting their different roles in AF pathogenesis. PMID- 27550972 TI - Correction to: Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. PMID- 27550973 TI - Correction to: On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF. PMID- 27550975 TI - Safe Sleep and Skin-to-Skin Care in the Neonatal Period for Healthy Term Newborns. AB - Skin-to-skin care (SSC) and rooming-in have become common practice in the newborn period for healthy newborns with the implementation of maternity care practices that support breastfeeding as delineated in the World Health Organization's "Ten Steps to Successful Breastfeeding." SSC and rooming-in are supported by evidence that indicates that the implementation of these practices increases overall and exclusive breastfeeding, safer and healthier transitions, and improved maternal infant bonding. In some cases, however, the practice of SSC and rooming-in may pose safety concerns, particularly with regard to sleep. There have been several recent case reports and case series of severe and sudden unexpected postnatal collapse in the neonatal period among otherwise healthy newborns and near fatal or fatal events related to sleep, suffocation, and falls from adult hospital beds. Although these are largely case reports, there are potential dangers of unobserved SSC immediately after birth and throughout the postpartum hospital period as well as with unobserved rooming-in for at-risk situations. Moreover, behaviors that are modeled in the hospital after birth, such as sleep position, are likely to influence sleeping practices after discharge. Hospitals and birthing centers have found it difficult to develop policies that will allow SSC and rooming-in to continue in a safe manner. This clinical report is intended for birthing centers and delivery hospitals caring for healthy newborns to assist in the establishment of appropriate SSC and safe sleep policies. PMID- 27550974 TI - Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association. AB - BACKGROUND: Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. METHODS AND RESULTS: For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. CONCLUSIONS: Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume <=25 g (100 cal or ~6 teaspoons) of added sugars per day and to avoid added sugars for children <2 years of age. Although added sugars most likely can be safely consumed in low amounts as part of a healthy diet, few children achieve such levels, making this an important public health target. PMID- 27550976 TI - Evaluation and Management of Children With Acute Mental Health or Behavioral Problems. Part II: Recognition of Clinically Challenging Mental Health Related Conditions Presenting With Medical or Uncertain Symptoms. PMID- 27550978 TI - Medication-Assisted Treatment of Adolescents With Opioid Use Disorders. AB - Opioid use disorder is a leading cause of morbidity and mortality among US youth. Effective treatments, both medications and substance use disorder counseling, are available but underused, and access to developmentally appropriate treatment is severely restricted for adolescents and young adults. Resources to disseminate available therapies and to develop new treatments specifically for this age group are needed to save and improve lives of youth with opioid addiction. PMID- 27550979 TI - Preventing Obesity and Eating Disorders in Adolescents. AB - Obesity and eating disorders (EDs) are both prevalent in adolescents. There are concerns that obesity prevention efforts may lead to the development of an ED. Most adolescents who develop an ED did not have obesity previously, but some teenagers, in an attempt to lose weight, may develop an ED. This clinical report addresses the interaction between obesity prevention and EDs in teenagers, provides the pediatrician with evidence-informed tools to identify behaviors that predispose to both obesity and EDs, and provides guidance about obesity and ED prevention messages. The focus should be on a healthy lifestyle rather than on weight. Evidence suggests that obesity prevention and treatment, if conducted correctly, do not predispose to EDs. PMID- 27550977 TI - Evaluation and Management of Children and Adolescents With Acute Mental Health or Behavioral Problems. Part I: Common Clinical Challenges of Patients With Mental Health and/or Behavioral Emergencies. PMID- 27550980 TI - Executive Summary: Evaluation and Management of Children and Adolescents With Acute Mental Health or Behavioral Problems. Part I: Common Clinical Challenges of Patients With Mental Health and/or Behavioral Emergencies. PMID- 27550981 TI - Parental Presence During Treatment of Ebola or Other Highly Consequential Infection. AB - This clinical report offers guidance to health care providers and hospitals on options to consider regarding parental presence at the bedside while caring for a child with suspected or proven Ebola virus disease (Ebola) or other highly consequential infection. Options are presented to help meet the needs of the patient and the family while also posing the least risk to providers and health care organizations. The optimal way to minimize risk is to limit contact between the person under investigation or treatment and family members/caregivers whenever possible while working to meet the emotional support needs of both patient and family. At times, caregiver presence may be deemed to be in the best interest of the patient, and in such situations, a strong effort should be made to limit potential risks of exposure to the caregiver, health care providers, and the community. The decision to allow parental/caregiver presence should be made in consultation with a team including an infectious diseases expert and state and/or local public health authorities and should involve consideration of many factors, depending on the stage of investigation and management, including (1) a careful history, physical examination, and investigations to elucidate the likelihood of the diagnosis of Ebola or other highly consequential infection; (2) ability of the facility to offer appropriate isolation for the person under investigation and family members and to manage Ebola; (3) ability to recognize and exclude people at increased risk of worse outcomes (eg, pregnant women); and (4) ability of parent/caregiver to follow instructions, including appropriate donning and doffing of personal protective equipment. PMID- 27550982 TI - Mind-Body Therapies in Children and Youth. AB - Mind-body therapies are popular and are ranked among the top 10 complementary and integrative medicine practices reportedly used by adults and children in the 2007 2012 National Health Interview Survey. A growing body of evidence supports the effectiveness and safety of mind-body therapies in pediatrics. This clinical report outlines popular mind-body therapies for children and youth and examines the best-available evidence for a variety of mind-body therapies and practices, including biofeedback, clinical hypnosis, guided imagery, meditation, and yoga. The report is intended to help health care professionals guide their patients to nonpharmacologic approaches to improve concentration, help decrease pain, control discomfort, or ease anxiety. PMID- 27550983 TI - Executive Summary: Evaluation and Management of Children With Acute Mental Health or Behavioral Problems. Part II: Recognition of Clinically Challenging Mental Health Related Conditions Presenting With Medical or Uncertain Symptoms. PMID- 27550984 TI - Child Restraint Use and Driver Screening in Fatal Crashes Involving Drugs and Alcohol. AB - BACKGROUND: There are reports that the incidence of alcohol-involved crashes has remained stable among fatally injured drivers while drug involvement has increased in recent years. METHODS: Data from the Fatality Analysis Reporting System (FARS) from 2010 to 2013 were used to examine drug and alcohol status of drivers (N = 10 864) of 4-wheeled passenger vehicles involved in a fatal crash while transporting a passenger aged 0 to 14 years (N = 17 179). Mixed effect multivariable logistic regression used SAS GLIMMIX to control for clustering. Odds ratios are reported with 95% confidence intervals (CIs). RESULTS: Only 28.9% of drivers were screened for both alcohol and drugs, and 56.7% were not tested for either. The total proportion of unrestrained child passengers increased nearly linearly by age. Findings ranged as high as 70% for 13- to 14-year-olds with drivers positive for drugs and alcohol. In multivariable adjusted models, inappropriate child seating with drivers who tested positive was as follows: alcohol, 1.30 (95% CI, 0.92-1.82); drugs, 1.54 (95% CI, 1.24-1.92); and for both drugs and alcohol, 1.88 (95% CI, 1.38-2.55). More than one-fourth were unrestrained with drivers positive for cannabis (27.7%). Overall mortality was approximately triple for unrestrained versus restrained (33.5% vs 11.5%; P < .0001) and was higher in front-seated than rear-seated passengers (40.7% vs 31.5%; P < .0001). CONCLUSIONS: Passengers were less likely to be appropriately seated and to be restrained when transported by a driver positive for drugs and alcohol, but this finding varied according to passenger age and drug/alcohol category. PMID- 27550985 TI - Industry Television Ratings for Violence, Sex, and Substance Use. AB - OBJECTIVE: To examine whether the industry-run television (TV) Parental Guidelines discriminate on violence, sexual behavior, alcohol use, and smoking in TV shows, to assess their usefulness for parents. METHODS: Seventeen TV shows (323 episodes and 9214 episode minutes) across several TV show rating categories (TVY7, TVPG, TV14, and TVMA) were evaluated. We content-coded the episodes, recording seconds of each risk behavior, and we rated the salience of violence in each one. Multilevel models were used to test for associations between TV rating categories and prevalence of risk behaviors across and within episodes or salience of violence. RESULTS: Every show had at least 1 risk behavior. Violence was pervasive, occurring in 70% of episodes overall and for 2.3 seconds per episode minute. Alcohol was also common (58% of shows, 2.3 seconds per minute), followed by sex (53% of episodes, 0.26 seconds per minute), and smoking (31% of shows, 0.54 seconds per minute). TV Parental Guidelines did not discriminate prevalence estimates of TV episode violence. Although TV-Y7 shows had significantly less substance use, other categories were poor at discriminating substance use, which was as common in TV-14 as TV-MA shows. Sex and gory violence were the only behaviors demonstrating a graded increase in prevalence and salience for older-child rating categories. CONCLUSIONS: TV Parental Guidelines ratings were ineffective in discriminating shows for 3 out of 4 behaviors studied. Even in shows rated for children as young as 7 years, violence was prevalent, prominent, and salient. TV ratings were most effective for identification of sexual behavior and gory violence. PMID- 27550986 TI - Post-exercise syncope: Wingate syncope test and visual-cognitive function. AB - Adequate cerebral perfusion is necessary to maintain consciousness in upright humans. Following maximal anaerobic exercise, cerebral perfusion can become compromised and result in syncope. It is unknown whether post-exercise reductions in cerebral perfusion can lead to visual-cognitive deficits prior to the onset of syncope, which would be of concern for emergency workers and warfighters, where critical decision making and intense physical activity are combined. Therefore, the purpose of this experiment was to determine if reductions in cerebral blood velocity, induced by maximal anaerobic exercise and head-up tilt, result in visual-cognitive deficits prior to the onset of syncope. Nineteen sedentary to recreationally active volunteers completed a symptom-limited 60 degrees head-up tilt for 16 min before and up to 16 min after a 60 sec Wingate test. Blood velocity of the middle cerebral artery was measured using transcranial Doppler ultrasound and a visual decision-reaction time test was assessed, with independent analysis of peripheral and central visual field responses. Cerebral blood velocity was 12.7 +/- 4.0% lower (mean +/- SE; P < 0.05) after exercise compared to pre-exercise. This was associated with a 63 +/- 29% increase (P < 0.05) in error rate for responses to cues provided to the peripheral visual field, without affecting central visual field error rates (P = 0.46) or decision reaction times for either visual field. These data suggest that the reduction in cerebral blood velocity following maximal anaerobic exercise contributes to visual-cognitive deficits in the peripheral visual field without an apparent affect to the central visual field. PMID- 27550987 TI - BMI1 is downregulated by the natural compound curcumin, but not by bisdemethoxycurcumin and dimethoxycurcumin. AB - The B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) locus encodes a 37-kD protein that is a key regulatory component of the polycomb regulatory complex 1 (PRC1). When overexpressed in various cancer types, the BMI1 protein induces cell growth and promotes tumor growth in vitro and in vivo. Curcumin, a major phytochemical in turmeric (Curcuma longa), inhibits the proliferation and survival of many types of cancer cells, both in vitro and in vivo, and has been reported to reduce BMI1 expression in breast cancer cells. In this study, effects of curcumin and two analogs (bisdemethoxycurcumin and dimethoxycurcumin) on BMI1 expression were evaluated in DLD-1 colorectal cancer cells. Bisdemethoxycurcumin (BDMC) is naturally occurring in turmeric, whereas dimethoxycurcumin (DMC) is a synthetic analog of curcumin. All three compounds reduced cell survival, but only the natural compound downregulated BMI1 protein expression; curcumin significantly reduced BMI1 levels more than bisdemethoxycurcumin and dimethoxycurcumin. In addition, curcumin and BDMC inhibit survival of the DLD-1 colorectal cancer cells by inducing apoptosis, whereas DMC inhibits survival by a mechanism other than apoptosis. PMID- 27550989 TI - The 2016 Garrod Lecture: The role of the healthcare epidemiologist in antimicrobial chemotherapy-a view from the USA. AB - Antimicrobial chemotherapy now spans 80 years and four generations. The healthcare epidemiologist has an important role to play in this field. Efforts focus in three areas: (i) minimizing the transmission of antimicrobial-resistant bacteria in healthcare settings (infection control); (ii) optimizing use of currently available antibacterial drugs (antibiotic stewardship); and (iii) recognizing and responding to opportunities for new drug development. For each area, the epidemiologist provides data that address four practical questions 'What is the problem?', 'What should be done?', 'Is it being done?' and 'Is it working?'. A team approach is crucial to acting on the epidemiological data. Examples are presented to illustrate different roles of the epidemiologist, and tools and measures that have been developed to address some problems of current importance. Monitoring of quality, integrity and security of data remains a major focus. The epidemiologist will continue to have a key role in antimicrobial chemotherapy. PMID- 27550988 TI - Acute resistance exercise-induced IGF1 expression and subsequent GLUT4 translocation. AB - Acute aerobic exercise (AE) is a major physiological stimulus for skeletal muscle glucose uptake through activation of 5' AMP-activated protein kinase (AMPK). However, the regulation of glucose uptake by acute resistance exercise (RE) remains unclear. To investigate the intracellular regulation of glucose uptake after acute RE versus acute AE, male Sprague-Dawley rats were divided into three groups: RE, AE, or nonexercise control. After fasting for 12 h overnight, the right gastrocnemius muscle in the RE group was exercised at maximum isometric contraction via percutaneous electrical stimulation (3 * 10 sec, 5 sets). The AE group ran on a treadmill (25 m/min, 60 min). Muscle samples were taken 0, 1, and 3 h after completion of the exercises. AMPK, Ca(2+)/calmodulin-dependent protein kinase II, and TBC1D1 phosphorylation were increased immediately after both forms of exercise and returned to baseline levels by 3 h. Muscle IGF1 expression was increased by RE but not AE, and maintained until 3 h after RE Additionally, Akt and AS160 phosphorylation were sustained for 3 h after RE, whereas they returned to baseline levels by 3 h after AE Similarly, GLUT4 translocation remained elevated 3 h after RE, although it returned to the baseline level by 3 h after AE Overall, this study showed that AMPK/TBC1D1 and IGF1/Akt/AS160 signaling were enhanced by acute RE, and that GLUT4 translocation after acute RE was more prolonged than after acute AE These results suggest that acute RE-induced increases in intramuscular IGF1 expression might be a distinct regulator of GLUT4 translocation. PMID- 27550990 TI - Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients. AB - Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%-60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors. PMID- 27550991 TI - ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. AB - The Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II: ). Real-time PCR is recommended for the routine diagnosis of PCP ( A-II: ). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value ( A II: ). Non-invasive specimens can be suitable alternatives ( B-II: ), acknowledging that PCP cannot be ruled out in case of a negative PCR result ( A II: ). Detecting beta-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP ( A-II: ). A negative serum beta-d-glucan result can exclude PCP in a patient at risk ( A-II: ), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks ( A-II: ). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended ( B-II: ) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies. PMID- 27550992 TI - ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. AB - The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen. PMID- 27550994 TI - Predictive Value of Positive Drug Screening Results in an Urban Outpatient Population. AB - Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results. We analyzed the results of confirmatory assays in an outpatient setting to determine the predictive value of presumptive positive urine drug screen results using an automated immunoassay for eight common drugs or drug classes. Positive predictive values (PPVs), in descending order, were as follows: cannabinoids (100%), cocaine (100%), opiates (86.8%), benzodiazepines (74.6%), oxycodone (67.6%), methadone (44.1%) and amphetamines (9.3%). The number of positive barbiturate results was too small to be included in the statistical analysis. PMID- 27550993 TI - ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV infected haematology patients. AB - The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis. PMID- 27550995 TI - Stability of 26 Sedative Hypnotics in Six Toxicological Matrices at Different Storage Conditions. AB - Forensic laboratories are challenged with backlogs that produce turnaround times that vary from days to months. Therefore, drug stability is important for interpretation in both antemortem (blood and urine) and postmortem (blood, brain, liver, stomach contents) cases. In this study, 23 benzodiazepines (2 hydroxyethylflurazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, alpha hydroxyalprazolam, alpha-hydroxytriazolam, alprazolam, bromazepam, chlordiazepoxide, clonazepam, demoxepam, desalkylflurazepam, diazepam, estazolam, flunitrazepam, flurazepam, lorazepam, midazolam, nitrazepam, nordiazepam, oxazepam, phenazepam, temazepam and triazolam) and three sedative hypnotics (zaleplon, zopiclone and zolpidem) were spiked into the six matrices at two different concentrations for each drug. The samples were stored in either a refrigerator (4 degrees C) or freezer (-20 degrees C) and analyzed in triplicate at various time intervals over an 8-month period using an SWGTOX validated method. The concentrations decreased over time regardless of the initial spiked concentration, and the storage conditions had little effect on the decrease of most drugs. Conversion from drug to metabolite was difficult to determine since all 26 drugs were present in each sample. Zopiclone and phenazepam were the least stable drugs; zopiclone was the only drug that completely disappeared in any matrix (both antemortem and postmortem blood). Urine was the most stable matrix with only phenazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, 2 hydroxyethylflurazepam, and zopiclone decreasing >20% over the 8 months in either storage condition. Postmortem blood, the least stable matrix, had only two drugs, zolpidem and bromazepam, decreasing <20% in the 8-month time period. Further experiments on stability of these drugs should be undertaken to remove the freeze thaw cycle effect and more thoroughly examining drug-metabolite conversion. PMID- 27550996 TI - Cytokinin Response Factor 6 Represses Cytokinin-Associated Genes during Oxidative Stress. AB - Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6 dependent genes and establishes a novel connection between cytokinin and oxidative stress response. PMID- 27550997 TI - Sporophyte Formation and Life Cycle Completion in Moss Requires Heterotrimeric G Proteins. AB - In this study, we report the functional characterization of heterotrimeric G proteins from a nonvascular plant, the moss Physcomitrella patens. In plants, G proteins have been characterized from only a few angiosperms to date, where their involvement has been shown during regulation of multiple signaling and developmental pathways affecting overall plant fitness. In addition to its unparalleled evolutionary position in the plant lineages, the P. patens genome also codes for a unique assortment of G-protein components, which includes two copies of Gbeta and Ggamma genes, but no canonical Galpha Instead, a single gene encoding an extra-large Galpha (XLG) protein exists in the P. patens genome. Here, we demonstrate that in P. patens the canonical Galpha is biochemically and functionally replaced by an XLG protein, which works in the same genetic pathway as one of the Gbeta proteins to control its development. Furthermore, the specific G-protein subunits in P. patens are essential for its life cycle completion. Deletion of the genomic locus of PpXLG or PpGbeta2 results in smaller, slower growing gametophores. Normal reproductive structures develop on these gametophores, but they are unable to form any sporophyte, the only diploid stage in the moss life cycle. Finally, the mutant phenotypes of DeltaPpXLG and DeltaPpGbeta2 can be complemented by the homologous genes from Arabidopsis, AtXLG2 and AtAGB1, respectively, suggesting an overall conservation of their function throughout the plant evolution. PMID- 27550998 TI - Systemic Induction of Photosynthesis via Illumination of the Shoot Apex Is Mediated Sequentially by Phytochrome B, Auxin and Hydrogen Peroxide in Tomato. AB - Systemic signaling of upper leaves promotes the induction of photosynthesis in lower leaves, allowing more efficient use of light flecks. However, the nature of the systemic signals has remained elusive. Here, we show that preillumination of the tomato (Solanum lycopersicum) shoot apex alone can accelerate photosynthetic induction in distal leaves and that this process is light quality dependent, where red light promotes and far-red light delays photosynthetic induction. Grafting the wild-type rootstock with a phytochome B (phyB) mutant scion compromised light-induced photosynthetic induction as well as auxin biosynthesis in the shoot apex, auxin signaling, and RESPIRATORY BURST OXIDASE HOMOLOG1 (RBOH1)-dependent hydrogen peroxide (H2O2) production in the systemic leaves. Light-induced systemic H2O2 production in the leaves of the rootstock also was absent in plants grafted with an auxin-resistant diageotropica (dgt) mutant scion. Cyclic electron flow around photosystem I and associated ATP production were increased in the systemic leaves by exposure of the apex to red light. This enhancement was compromised in the systemic leaves of the wild-type rootstock with phyB and dgt mutant scions and also in RBOH1-RNA interference leaves with the wild type as scion. Silencing of ORANGE RIPENING, which encodes NAD(P)H dehydrogenase, compromised the systemic induction of photosynthesis. Taken together, these results demonstrate that exposure to red light triggers phyB mediated auxin synthesis in the apex, leading to H2O2 generation in systemic leaves. Enhanced H2O2 levels in turn activate cyclic electron flow and ATP production, leading to a faster induction of photosynthetic CO2 assimilation in the systemic leaves, allowing plants better adaptation to the changing light environment. PMID- 27550999 TI - Therapeutic Inhibition of the MDM2-p53 Interaction Prevents Recurrence of Adenoid Cystic Carcinomas. AB - Purpose: Conventional chemotherapy has modest efficacy in advanced adenoid cystic carcinomas (ACC). Tumor recurrence is a major challenge in the management of ACC patients. Here, we evaluated the antitumor effect of a novel small-molecule inhibitor of the MDM2-p53 interaction (MI-773) combined with cisplatin in patient derived xenograft (PDX) ACC tumors.Experimental Design: Therapeutic strategies with MI-773 and/or cisplatin were evaluated in SCID mice harboring PDX ACC tumors (UM-PDX-HACC-5) and in low passage primary human ACC cells (UM-HACC-2A, -2B, -5, 6) in vitro The effect of therapy on the fraction of cancer stem cells (CSC) was determined by flow cytometry for ALDH activity and CD44 expression.Results: Combined therapy with MI-773 with cisplatin caused p53 activation, induction of apoptosis, and regression of ACC PDX tumors. Western blots revealed induction of MDM2, p53 and downstream p21 expression, and regulation of apoptosis-related proteins PUMA, BAX, Bcl-2, Bcl-xL, and active caspase-9 upon MI-773 treatment. Both single-agent MI-773 and MI-773 combined with cisplatin decreased the fraction of CSCs in PDX ACC tumors. Notably, neoadjuvant MI-773 and surgery eliminated tumor recurrences during a postsurgical follow-up of more than 300 days. In contrast, 62.5% of mice that received vehicle control presented with palpable tumor recurrences within this time period (P = 0.0097).Conclusions: Collectively, these data demonstrate that therapeutic inhibition of MDM2-p53 interaction by MI-773 decreased the CSC fraction, sensitized ACC xenograft tumors to cisplatin, and eliminated tumor recurrence. These results suggest that patients with ACC might benefit from the therapeutic inhibition of the MDM2-p53 interaction. Clin Cancer Res; 23(4); 1036-48. (c)2016 AACR. PMID- 27551001 TI - Biospecimen Complexity-the Next Challenge for Cancer Research Biobanks? AB - Purpose: Biospecimens (e.g., tissues, bloods, fluids) are critical for translational cancer research to generate the necessary knowledge to guide implementation of precision medicine. Rising demand and the need for higher quality biospecimens are already evident.Experimental Design: The recent increase in requirement for biospecimen complexity in terms of linked biospecimen types, multiple preservation formats, and longitudinal data was explored by assessing trends in cancer research publications from 2000 to 2014.Results: A PubMed search shows that there has been an increase in both raw numbers and the relative proportion (adjusted for total numbers of articles in each period) of the subgroups of articles typically associated with the use of biospecimens and both dense treatment and/or outcomes data and multiple biospecimen formats.Conclusions: Increasing biospecimen complexity is a largely unrecognized and new pressure on cancer research biobanks. New approaches to cancer biospecimen resources are needed such as the implementation of more efficient and dynamic consent mechanisms, stronger participant involvement in biobank governance, development of requirements for registration of collections, and models to establish stock targets for biobanks. In particular, the latter two approaches would enable funders to establish a better balance between biospecimen supply and research demand, reduce expenditure on duplicate collections, and encourage increased efficiency of biobanks to respond to the research need for more complex cases. This in turn would also enable biobanks to focus more on quality and standardization that are surely factors in the even more important arena of research reproducibility. Clin Cancer Res; 23(4); 894-8. (c)2016 AACR. PMID- 27551000 TI - A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia. AB - Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML).Results: A total of 99 patients received veliparib 10-100 mg orally twice daily on days 1-8, 1-14, or 1-21 along with continuous infusion topotecan 1.0-1.2 mg/m2/d + carboplatin 120-150 mg/m2/d on days 3-7. The MTD was veliparib 80 mg twice daily for up to 21 days with topotecan 1.2 mg/m2/d + carboplatin 150 mg/m2/d. Mucositis was dose limiting and correlated with high veliparib concentrations. The response rate was 33% overall (33/99: 14 CR, 11 CRi, 8 PR) but was 64% (14/22) for patients with antecedent or associated aggressive MPNs or CMML. Leukemias with baseline DNA repair defects, as evidenced by impaired DNA damage-induced FANCD2 monoubiquitination, had improved survival [HR = 0.56 (95% confidence interval, 0.27-0.92)]. A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX phosphorylation in CD34+ leukemia cells, with greater phosphorylation in cells from responders.Conclusions: The veliparib/topotecan/carboplatin combination warrants further investigation, particularly in patients with aggressive MPNs, CMML, and MPN- or CMML-related acute leukemias. Clin Cancer Res; 23(4); 899-907. (c)2016 AACR. PMID- 27551002 TI - Found in Translation: Maximizing the Clinical Relevance of Nonclinical Oncology Studies. AB - Purpose: The translation of nonclinical oncology studies is a subject of continuous debate. We propose that translational oncology studies need to optimize both pharmacokinetic (drug exposure) and pharmacodynamic (xenograft model) aspects. While improvements in pharmacodynamic translatability can be obtained by choosing cell lines or patient-derived xenograft models closer to the clinical indication, significant ambiguity and variability exists when optimizing the pharmacokinetic translation of small molecule and biotherapeutic agents.Experimental Design and Results: In this work, we propose a pharmacokinetic-based strategy to select nonclinical doses for approved drug molecules. We define a clinically relevant dose (CRD) as the dosing regimen in mice that most closely approximates the relevant pharmacokinetic metric in humans. Such metrics include area under the time-concentration curve and maximal or minimal concentrations within the dosing interval. The methodology is applied to six drugs, including targeted agents and chemotherapeutics, small and large molecules (erlotinib, dasatinib, vismodegib, trastuzumab, irinotecan, and capecitabine). The resulting efficacy response at the CRD is compared with clinical responses.Conclusions: We conclude that nonclinical studies designed with the appropriate CRDs of approved drug molecules will maximize the translatability of efficacy results, which is critical when testing approved and investigational agents in combination. Clin Cancer Res; 23(4); 1080-90. (c)2016 AACR. PMID- 27551004 TI - Correction. PMID- 27551005 TI - Zika Virus: From Obscurity to Potentially Devastating International Threat. PMID- 27551006 TI - CRISPR-Cas9 System: Opportunities and Concerns. PMID- 27551007 TI - Prevalence of Barriers and Facilitators to Enhancing Conservative Kidney Management for Older Adults in the Primary Care Setting. AB - BACKGROUND AND OBJECTIVES: Conservative management of adults with stage 5 CKD (eGFR<15 ml/min per 1.73 m2) is increasingly being provided in the primary care setting. We aimed to examine perceived barriers and facilitators for conservative management of older adults by primary care physicians. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In 2015, we conducted a cross-sectional, population based survey of all primary care physicians in Alberta, Canada. Eligible participants had experience caring for adults ages >=75 years old with stage 5 CKD not planning on initiating dialysis. Questionnaire items were on the basis of a qualitative descriptive study informed by the Behavior Change Wheel and tested for face and content validity. Physicians were contacted via postal mail and/or fax on the basis of a modified Dillman method. RESULTS: Four hundred nine eligible primary care physicians completed the questionnaire (9.6% response rate). The majority of respondents were men (61.6%), were ages 40-60 years old (62.6%), and practiced in a large/medium population center (68.0%). The most common barrier to providing conservative care in the primary care setting was the inability to access support to maintain patients in the home setting (39.1% of respondents; 95% confidence interval, 34.6% to 43.6%). The second most common barrier was working with nonphysician providers with limited kidney-specific clinical expertise (32.3%; 95% confidence interval, 28.0% to 36.7%). Primary care physicians indicated that the two most common strategies that would enhance their ability to provide conservative management would be the ability to use the telephone to contact a nephrologist or clinical staff from the conservative care clinic (86.9%; 95% confidence interval, 83.7% to 90.0% and 85.6%; 95% confidence interval, 82.4% to 88.9%, respectively). CONCLUSIONS: We identified important areas to inform clinical programs to reduce barriers and enhance facilitators to improve primary care physicians' provision of conservative kidney care. In particular, primary care physicians require additional resources for maintaining patients in their home and telephone access to nephrologists and conservative care specialists. PMID- 27551009 TI - Agar Bioassays for Antifungals in Combination Therapy. PMID- 27551008 TI - Successful Treatment of Bloodstream Infection Due to Metallo-beta-Lactamase Producing Stenotrophomonas maltophilia in a Renal Transplant Patient. AB - Stenotrophomonas maltophilia is an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-beta-lactamase-producing S. maltophilia refractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient's S. maltophilia isolate. PMID- 27551010 TI - Reply to "Agar Bioassays for Antifungals in Combination Therapy". PMID- 27551012 TI - Metastatic Breast Cancer With ESR1 Mutation: Clinical Management Considerations From the Molecular and Precision Medicine (MAP) Tumor Board at Massachusetts General Hospital. AB - : The last decade in oncology has witnessed impressive response rates with targeted therapies, largely because of collaborative efforts at understanding tumor biology and careful patient selection based on molecular fingerprinting of the tumor. Consequently, there has been a push toward routine molecular genotyping of tumors, and large precision medicine-based clinical trials have been launched to match therapy to the molecular alteration seen in a tumor. However, selecting the "right drug" for an individual patient in clinic is a complex decision-making process, including analytical interpretation of the report, consideration of the importance of the molecular alteration in driving growth of the tumor, tumor heterogeneity, the availability of a matched targeted therapy, efficacy and toxicity considerations of the targeted therapy (compared with standard therapy), and reimbursement issues. In this article, we review the key considerations involved in clinical decision making while reviewing a molecular genotyping report. We present the case of a 67-year-old postmenopausal female with metastatic estrogen receptor-positive (ER+) breast cancer, whose tumor progressed on multiple endocrine therapies. Molecular genotyping of the metastatic lesion revealed the presence of an ESR1 mutation (encoding p.Tyr537Asn), which was absent in the primary tumor. The same ESR1 mutation was also detected in circulating tumor DNA (ctDNA) extracted from her blood. The general approach for interpretation of genotyping results, the clinical significance of the specific mutation in the particular cancer, potential strategies to target the pathway, and implications for clinical practice are reviewed in this article. KEY POINTS: ER+ breast tumors are known to undergo genomic evolution during treatment with the acquisition of new mutations that confer resistance to treatment.ESR1 mutations in the ligand-binding domain of ER can lead to a ligand-independent, constitutively active form of ER and mediate resistance to aromatase inhibitors.ESR1 mutations may be detected by genomic sequencing of tissue biopsies of the metastatic tumor or by sequencing the circulating tumor cells or tumor DNA (ctDNA).Sequencing results may lead to a therapeutic "match" with an existing FDA-approved drug or match with an experimental agent that fits the clinical setting. PMID- 27551014 TI - A Touchy Subject: Can Physicians Improve Value by Discussing Costs and Clinical Benefits With Patients? PMID- 27551013 TI - Use and Yield of Baseline Imaging and Laboratory Testing in Stage II Breast Cancer. AB - BACKGROUND: Despite guideline recommendations, baseline laboratory testing and advanced imaging are widely ordered in clinical practice to stage asymptomatic patients with clinical stage II breast cancer (BC). MATERIALS AND METHODS: A retrospective study at two academic centers in Boston, Massachusetts, between 2006 and 2007 explored the use, results, and implications of laboratory tests, tumor markers, and imaging in patients with clinical stage II BC. RESULTS: Among 411 patients, 233 (57%) had liver function testing, 134 (33%) had tumor marker tests, and 237 (58%) had computed tomography (CT) as part of their initial diagnostic workup. Median age was 52 (range, 23-90 years). On multivariable analysis, young age, more advanced stage, and tumor subtype (human epidermal growth receptor-positive [HER2+] and triple-negative breast cancer [TNBC]) were significantly associated with baseline CT. The rate of detection of true metastatic disease with use of baseline staging imaging was 2.1% (95% confidence interval, 0.7%-5%). It was 2.2% (3 of 135) for estrogen receptor/progesterone receptor-positive disease, 1.9% (1 of 54) for HER2+ disease, and 2.1% (1 of 48) for TNBC. At 5 years of follow-up, 46 of 406 patients were diagnosed with metastatic breast cancer. Thirty-four of 46 (73.9%) who developed recurrent disease had imaging at their initial diagnosis, and of these, five had abnormalities on their initial imaging that was correlated with where they developed metastatic disease. CONCLUSION: In this cohort of women with stage II BC, staging imaging at diagnosis had a low yield in detecting distant metastases (2.1%). The detection rate was not higher with HER2+ disease or TNBC, despite the trend that patients with these subtypes were more likely to undergo imaging. IMPLICATIONS FOR PRACTICE: Despite guideline recommendations, asymptomatic patients with stage II breast cancer (BC) often undergo staging imaging with computed tomography, bone scanning, or positron emission tomography. Physicians have often reported that they order imaging despite recommendations because they believe that younger patients or patients with more aggressive BC phenotypes, such as human epidermal receptor 2-positive BC or triple-negative BC, benefit from staging imaging. In this cohort of women younger than those in prior studies, the yield of detecting distant metastatic disease in patients with clinical stage II BC was very low and the detection rate was not higher in the presence of HER2-positive or triple-negative BC. PMID- 27551015 TI - Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols. AB - The enzyme catalyzing the ring-contracting conversion of the flavanonol taxifolin to the auronol alphitonin in the course of flavonoid degradation by the human intestinal anaerobe Eubacterium ramulus was purified and characterized. It stereospecifically catalyzed the isomerization of (+)-taxifolin but not that of ( )-taxifolin. The Km for (+)-taxifolin was 6.4 +/- 0.8 MUM, and the Vmax was 108 +/- 4 MUmol min-1 (mg protein)-1 The enzyme also isomerized (+) dihydrokaempferol, another flavanonol, to maesopsin. Inspection of the encoding gene revealed its complete identity to that of the gene encoding chalcone isomerase (CHI) from E. ramulus Based on the reported X-ray crystal structure of CHI (M. Gall et al., Angew Chem Int Ed 53:1439-1442, 2014, http://dx.doi.org/10.1002/anie.201306952), docking experiments suggest the substrate binding mode of flavanonols and their stereospecific conversion. Mutation of the active-site histidine (His33) to alanine led to a complete loss of flavanonol isomerization by CHI, which indicates that His33 is also essential for this activity. His33 is proposed to mediate the stereospecific abstraction of a proton from the hydroxymethylene carbon of the flavanonol C-ring followed by ring opening and recyclization. A flavanonol-isomerizing enzyme was also identified in the flavonoid-converting bacterium Flavonifractor plautii based on its 50% sequence identity to the CHI from E. ramulus IMPORTANCE: Chalcone isomerase was known to be involved in flavone/flavanone conversion by the human intestinal bacterium E. ramulus Here we demonstrate that this enzyme moreover catalyzes a key step in the breakdown of flavonols/flavanonols. Thus, a single isomerase plays a dual role in the bacterial conversion of dietary bioactive flavonoids. The identification of a corresponding enzyme in the human intestinal bacterium F. plautii suggests a more widespread occurrence of this isomerase in flavonoid-degrading bacteria. PMID- 27551017 TI - Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7. AB - : Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. IMPORTANCE: Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1->RpoH2 >CrtE2 and RpoE2->RpoH1->CrtE2 cascades in A. brasilense It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. PMID- 27551016 TI - ZpdN, a Plasmid-Encoded Sigma Factor Homolog, Induces pBS32-Dependent Cell Death in Bacillus subtilis. AB - : The ancestral Bacillus subtilis strain 3610 contains an 84-kb plasmid called pBS32 that was lost during domestication of commonly used laboratory derivatives. Here we demonstrate that pBS32, normally present at 1 or 2 copies per cell, increases in copy number nearly 100-fold when cells are treated with the DNA damaging agent mitomycin C. Mitomycin C treatment also caused cell lysis dependent on pBS32-borne prophage genes. ZpdN, a sigma factor homolog encoded by pBS32, was required for the plasmid response to DNA damage, and artificial expression of ZpdN was sufficient to induce pBS32 hyperreplication and cell death. Plasmid DNA released by cell death was protected by the capsid protein ZpbH, suggesting that the plasmid was packaged into a phagelike particle. The putative particles were further indicated by CsCl sedimentation but were not observed by electron microscopy and were incapable of killing B. subtilis cells extracellularly. We hypothesize that pBS32-mediated cell death releases a phagelike particle that is defective and unstable. IMPORTANCE: Prophages are phage genomes stably integrated into the host bacterium's chromosome and less frequently are maintained as extrachromosomal plasmids. Here we report that the extrachromosomal plasmid pBS32 of Bacillus subtilis encodes a prophage that, when activated, kills the host. pBS32 also encodes both the sigma factor homolog ZpdN that is necessary and sufficient for prophage induction and the protein ComI, which is a potent inhibitor of DNA uptake by natural transformation. We provide evidence that the entire pBS32 sequence may be part of the prophage and thus that competence inhibition may be linked to lysogeny. PMID- 27551018 TI - Impact of LytR-CpsA-Psr Proteins on Cell Wall Biosynthesis in Corynebacterium glutamicum. AB - : Proteins of the LCP (LytR, CpsA, Psr) family have been shown to inherit important roles in bacterial cell wall biosynthesis. However, their exact function in the formation of the complex cell wall structures of the Corynebacteriales, including the prominent pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae, remains unclear. Here, we analyzed the role of the LCP proteins LcpA and LcpB of Corynebacterium glutamicum, both of which localize at regions of nascent cell wall biosynthesis. A strain lacking lcpB did not show any growth-related or morphological phenotype under the tested conditions. In contrast, conditional silencing of the essential lcpA gene resulted in severe growth defects and drastic morphological changes. Compared to the wild-type cell wall, the cell wall of this mutant contained significantly less mycolic acids and a reduced amount of arabinogalactan. In particular, rhamnose, a specific sugar component of the linker that connects arabinogalactan and peptidoglycan, was decreased. Complementation studies of the lcpA-silencing strain with several mutated and truncated LcpA variants suggested that both periplasmic domains are essential for function whereas the cytoplasmic N-terminal part is dispensable. Successful complementation experiments with proteins of M. tuberculosis and C. diphtheriae revealed a conserved function of LCP proteins in these species. Finally, pyrophosphatase activity of LcpA was shown in an in vitro assay. Taken together, our results suggest that LCP proteins are responsible for the transfer of arabinogalactan onto peptidoglycan in actinobacterial species and support a crucial function of a so-far-uncharacterized C-terminal domain (LytR_C domain) which is frequently found at the C terminus of the LCP domain in this prokaryotic phylum. IMPORTANCE: About one-third of the world's population is infected with Mycobacterium tuberculosis, and multiple-antibiotic resistance provokes the demand for novel antibiotics. The special cell wall architecture of Corynebacteriales is critical for treatments because it is either a direct target or a barrier that the drug has to cross. Here, we present the analysis of LcpA and LcpB of the closely related Corynebacterium glutamicum, the first of which is an essential protein involved in cell wall biogenesis. Our work provides a comprehensive characterization of the impact of LCP proteins on cell wall biogenesis in this medically and biotechnologically important class of bacteria. Special focus is set on the two periplasmic LcpA domains and their contributions to physiological function. PMID- 27551019 TI - Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli. AB - : Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrC lacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. IMPORTANCE: Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower-affinity mRNA targets, thus eliciting major shifts in the bacterial lifestyle. CsrB/C transcription and turnover are activated by carbon metabolism products (e.g., formate and acetate) and by a preferred carbon source (glucose), respectively. We show that cAMP-CRP, a mediator of classical catabolite repression, inhibits csrC transcription by binding to the upstream region of this gene and also inhibits csrB transcription, apparently indirectly. We propose that glucose availability activates pathways for both synthesis and turnover of CsrB/C, thus shaping the dynamics of global signaling in response to the nutritional environment by poising CsrB/C sRNA levels for rapid response. PMID- 27551020 TI - Neisseria gonorrhoeae Crippled Its Peptidoglycan Fragment Permease To Facilitate Toxic Peptidoglycan Monomer Release. AB - : Neisseria gonorrhoeae (gonococci) and Neisseria meningitidis (meningococci) are human pathogens that cause gonorrhea and meningococcal meningitis, respectively. Both N. gonorrhoeae and N. meningitidis release a number of small peptidoglycan (PG) fragments, including proinflammatory PG monomers, although N. meningitidis releases fewer PG monomers. The PG fragments released by N. gonorrhoeae and N. meningitidis are generated in the periplasm during cell wall remodeling, and a majority of these fragments are transported into the cytoplasm by an inner membrane permease, AmpG; however, a portion of the PG fragments are released into the extracellular environment through unknown mechanisms. We previously reported that the expression of meningococcal ampG in N. gonorrhoeae reduced PG monomer release by gonococci. This finding suggested that the efficiency of AmpG-mediated PG fragment recycling regulates the amount of PG fragments released into the extracellular milieu. We determined that three AmpG residues near the C-terminal end of the protein modulate AmpG's efficiency. We also investigated the association between PG fragment recycling and release in two species of human associated nonpathogenic Neisseria: N. sicca and N. mucosa Both N. sicca and N. mucosa release lower levels of PG fragments and are more efficient at recycling PG fragments than N. gonorrhoeae Our results suggest that N. gonorrhoeae has evolved to increase the amounts of toxic PG fragments released by reducing its PG recycling efficiency. IMPORTANCE: Neisseria gonorrhoeae and Neisseria meningitidis are human pathogens that cause highly inflammatory diseases, although N. meningitidis is also frequently found as a normal member of the nasopharyngeal microbiota. Nonpathogenic Neisseria, such as N. sicca and N. mucosa, also colonize the nasopharynx without causing disease. Although all four species release peptidoglycan fragments, N. gonorrhoeae is the least efficient at recycling and releases the largest amount of proinflammatory peptidoglycan monomers, partly due to differences in the recycling permease AmpG. Studying the interplay between bacterial physiology (peptidoglycan metabolism) and pathogenesis (release of toxic monomers) leads to an increased understanding of how different bacterial species maintain asymptomatic colonization or cause disease and may contribute to efforts to mitigate disease. PMID- 27551021 TI - The Coordinated Positive Regulation of Topoisomerase Genes Maintains Topological Homeostasis in Streptomyces coelicolor. AB - : Maintaining an optimal level of chromosomal supercoiling is critical for the progression of DNA replication and transcription. Moreover, changes in global supercoiling affect the expression of a large number of genes and play a fundamental role in adapting to stress. Topoisomerase I (TopA) and gyrase are key players in the regulation of bacterial chromosomal topology through their respective abilities to relax and compact DNA. Soil bacteria such as Streptomyces species, which grow as branched, multigenomic hyphae, are subject to environmental stresses that are associated with changes in chromosomal topology. The topological fluctuations modulate the transcriptional activity of a large number of genes and in Streptomyces are related to the production of antibiotics. To better understand the regulation of topological homeostasis in Streptomyces coelicolor, we investigated the interplay between the activities of the topoisomerase-encoding genes topA and gyrBA We show that the expression of both genes is supercoiling sensitive. Remarkably, increased chromosomal supercoiling induces the topA promoter but only slightly influences gyrBA transcription, while DNA relaxation affects the topA promoter only marginally but strongly activates the gyrBA operon. Moreover, we showed that exposure to elevated temperatures induces rapid relaxation, which results in changes in the levels of both topoisomerases. We therefore propose a unique mechanism of S. coelicolor chromosomal topology maintenance based on the supercoiling-dependent stimulation, rather than repression, of the transcription of both topoisomerase genes. These findings provide important insight into the maintenance of topological homeostasis in an industrially important antibiotic producer. IMPORTANCE: We describe the unique regulation of genes encoding two topoisomerases, topoisomerase I (TopA) and gyrase, in a model Streptomyces species. Our studies demonstrate the coordination of topoisomerase gene regulation, which is crucial for maintenance of topological homeostasis. Streptomyces species are producers of a plethora of biologically active secondary metabolites, including antibiotics, antitumor agents, and immunosuppressants. The significant regulatory factor controlling the secondary metabolism is the global chromosomal topology. Thus, the investigation of chromosomal topology homeostasis in Streptomyces strains is crucial for their use in industrial applications as producers of secondary metabolites. PMID- 27551023 TI - Diagnosis Threat and Injury Beliefs After Mild Traumatic Brain Injury. AB - BACKGROUND: Diagnosis threat is a psychosocial factor proposed to contribute to poor cognitive outcomes following mild traumatic brain injury (mTBI). The current research explored diagnosis threat impact on objective and subjective cognitive performance in a "high risk" population of athletes. Two possible moderators of diagnosis threat - injury beliefs and suggestibility - were also investigated. METHOD: Seventy-six participants with a history of mTBI were recruited through sports clubs and randomized to a months threat group (instructions drew attention to mTBI history) or a control group (no mention of mTBI). They completed a battery of neuropsychological tests and questionnaires regarding day-to-day cognitive abilities. Measures of depression, anxiety, illness beliefs and suggestibility were also collected. RESULTS: No significant group differences were found on any neuropsychological tasks, nor on self-report of cognitive difficulties. Illness beliefs were not found to play a moderating role in general, although the majority of the study sample did not report negative mTBI beliefs and expectations: concern about the consequences of injury was associated with weaker performance on one test, WAIS-III Digit Span performance. Suggestibility was also found to have a significant affect on this test. CONCLUSIONS: Diagnosis threat did not appear to have a marked affect on objective or subjective cognitive performance after mTBI in athletes. Differing injury beliefs between the study's athlete population and the general population is a possible explanation for different findings in the area. This and other sources of potential variation in the affect of diagnosis threat are discussed. PMID- 27551022 TI - Chromatin Immunoprecipitation Sequencing Technology Reveals Global Regulatory Roles of Low-Cell-Density Quorum-Sensing Regulator AphA in the Pathogen Vibrio alginolyticus. AB - : Quorum sensing (QS) is an important regulatory system in virulence expression and environmental adaptation in bacteria. The master QS regulators (MQSR) LuxR and AphA reciprocally control QS gene expression in vibrios. However, the molecular basis for the regulatory functions of AphA remains undefined. In this study, we characterized its regulatory roles in Vibrio alginolyticus, an important zoonotic pathogen causing diseases in marine animals as well as in humans. AphA is involved in the motility ability, biofilm formation, and in vivo survival of V. alginolyticus Specifically, AphA is expressed at low-cell-density growth phases. In addition, AphA negatively regulates the expression of the main virulence factor, alkaline serine protease (Asp), through LuxR. Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) detected 49 enriched loci harboring AphA-binding peaks across the V. alginolyticus genome. An AphA-specific binding motif was identified and further confirmed by electrophoretic mobility shift assay (EMSA) and mutagenesis analysis. A quantitative real-time PCR (qRT-PCR) assay further validated the regulation of AphA on these genes. AphA binds directly to the aphA promoter and negatively regulates its own expression. Moreover, AphA directly regulates genes encoding adenylate cyclase, anti-sigmaD, FabR, and the small RNA CsrB, revealing versatile regulatory roles of AphA in its physiology and virulence. Furthermore, our data indicated that AphA modulates motility through the coordinated function of LuxR and CsrB. Collectively, the findings of this work contribute to better understanding of the regulatory roles of AphA in QS and non-QS genes. IMPORTANCE: In this work, we determined that AphA, the master regulator of QS at low cell density, plays essential roles in expression of genes associated with physiology and virulence in V. alginolyticus, a Gram-negative pathogen for humans and marine animals. We further uncovered that 49 genes could be directly regulated by AphA and a 19-bp consensus binding sequence was identified. Among the 49 genes, the QS and other non-QS-associated genes were identified to be regulated by AphA. Besides, the small RNA CsrB was negatively regulated by AphA, and AphA regulate motility abilities through both CsrB and LuxR. Taken together, the findings of this study improve our understanding of the complex regulation network of AphA and QS. PMID- 27551025 TI - Automated Office Blood Pressure-Incorporating SPRINT Into Clinical Practice. PMID- 27551024 TI - Assessment of Healthcare Decision-making Capacity. AB - It is often necessary for neuropsychologists, clinical psychologists, and other healthcare professionals to assess an individual's capacity to consent to treatment related to healthcare. This task can be challenging and requires a delicate balance of both respect for individuals' autonomy, as well as the protection of individuals with diminished capacity to make an autonomous decision. The purpose of the present review is to provide an overview of the conceptual model of decisional capacity as well as a brief summary of some of the currently available instruments designed to help evaluate medical decision making. In addition, current empirical literature on the relationship between neuropsychological abilities and decision-making capacity is discussed and a brief set of recommendations is provided to further aid clinicians or consultants when they are required to complete the ethically important but difficult task of making determinations about healthcare decision-making capacity. PMID- 27551026 TI - Root biomass, turnover and net primary productivity of a coffee agroforestry system in Costa Rica: effects of soil depth, shade trees, distance to row and coffee age. AB - BACKGROUND AND AIMS: In Costa Rica, coffee (Coffea arabica) plants are often grown in agroforests. However, it is not known if shade-inducing trees reduce coffee plant biomass through root competition, and hence alter overall net primary productivity (NPP). We estimated biomass and NPP at the stand level, taking into account deep roots and the position of plants with regard to trees. METHODS: Stem growth and root biomass, turnover and decomposition were measured in mixed coffee/tree (Erythrina poeppigiana) plantations. Growth ring width and number at the stem base were estimated along with stem basal area on a range of plant sizes. Root biomass and fine root density were measured in trenches to a depth of 4 m. To take into account the below-ground heterogeneity of the agroforestry system, fine root turnover was measured by sequential soil coring (to a depth of 30 cm) over 1 year and at different locations (in full sun or under trees and in rows/inter-rows). Allometric relationships were used to calculate NPP of perennial components, which was then scaled up to the stand level. KEY RESULTS: Annual ring width at the stem base increased up to 2.5 mm yr 1 with plant age (over a 44-year period). Nearly all (92 %) coffee root biomass was located in the top 1.5 m, and only 8 % from 1.5 m to a depth of 4 m. Perennial woody root biomass was 16 t ha-1 and NPP of perennial roots was 1.3 t ha-1 yr-1 Fine root biomass (0-30 cm) was two-fold higher in the row compared with between rows. Fine root biomass was 2.29 t ha-1 (12 % of total root biomass) and NPP of fine roots was 2.96 t ha-1 yr-1 (69 % of total root NPP). Fine root turnover was 1.3 yr-1 and lifespan was 0.8 years. CONCLUSIONS: Coffee root systems comprised 49 % of the total plant biomass; such a high ratio is possibly a consequence of shoot pruning. There was no significant effect of trees on coffee fine root biomass, suggesting that coffee root systems are very competitive in the topsoil. PMID- 27551027 TI - Spatiotemporal heterogeneity in precipitation patterns explain population-level germination strategies in an edaphic specialist. AB - BACKGROUND AND AIMS: Many locally endemic species in biodiversity hotspots are restricted to edaphic conditions that are fixed in the landscape, limiting their potential to track climate change through dispersal. Instead, such species experience strong selection for germination strategies that can track suitable conditions through time. Germination strategies were compared among populations across the geographic range of a California vernal pool annual, Lasthenia fremontii Local germination strategies were tested to determine the associations with geographic variation in precipitation patterns. METHODS: This study evaluated patterns of seed germination, dormancy and mortality in response to simulated variation in the timing, amount and duration of the first autumn precipitation event using seeds from six populations that span a geographic gradient in precipitation. Next, it was tested whether the germination strategies of different populations can be predicted by historical precipitation patterns that characterize each site. KEY RESULTS: A significant positive relationship was observed between the historical variability in autumn precipitation and the extent of dormancy in a population. Marginal populations, with histories of the most extreme but constant autumn precipitation levels, expressed the lowest dormancy levels. Populations from sites with historically higher levels of autumn precipitation tended to germinate faster, but this tendency was not statistically significant. CONCLUSIONS: Germination in L. fremontii is cued by the onset of the first rains that characterize the beginning of winter in California's Great Central Valley. However, populations differ in how fast they germinate and the fraction of seeds that remain dormant when germination cues occur. The results suggest that seed dormancy may be a key trait for populations to track increasingly drier climates predicted by climate change models. However, the low dormancy and high mortality levels observed among seeds of the southernmost, driest populations make them most vulnerable to local extinction. PMID- 27551028 TI - Contrasting germination responses to vegetative canopies experienced in pre- vs. post-dispersal environments. AB - BACKGROUND: Seeds adjust their germination based on conditions experienced before and after dispersal. Post-dispersal cues are expected to be more accurate predictors of offspring environments, and thus offspring success, than pre dispersal cues. Therefore, germination responses to conditions experienced during seed maturation may be expected to be superseded by responses to conditions experienced during seed imbibition. In taxa of disturbed habitats, neighbours frequently reduce the performance of germinants. This leads to the hypotheses that a vegetative canopy will reduce germination in such taxa, and that a vegetative canopy experienced during seed imbibition will over-ride germination responses to a canopy experienced during seed maturation, since it is a more proximal cue of immediate competition. These hypotheses were tested here in Arabidopsis thaliana METHODS: Seeds were matured under a simulated canopy (green filter) or white light. Fresh (dormant) seeds were imbibed in the dark, white light or canopy at two temperatures (10 or 22 degrees C), and germination proportions were recorded. Germination was also recorded in after-ripened (less dormant) seeds that were induced into secondary dormancy and imbibed in the dark at each temperature, either with or without brief exposure to red and far-red light. KEY RESULTS: Unexpectedly, a maturation canopy expanded the conditions that elicited germination, even as seeds lost and regained dormancy. In contrast, an imbibition canopy impeded or had no effect on germination. Maturation under a canopy did not modify germination responses to red and far-red light. Seed maturation under a canopy masked genetic variation in germination. CONCLUSIONS: The results challenge the hypothesis that offspring will respond more strongly to their own environment than to that of their parents. The observed relaxation of germination requirements caused by a maturation canopy could be maladaptive for offspring by disrupting germination responses to light cues after dispersal. Alternatively, reduced germination requirements could be adaptive by allowing seeds to germinate faster and reduce competition in later stages even though competition is not yet present in the seedling environment. The masking of genetic variation by maturation under a canopy, moreover, could impede evolutionary responses to selection on germination. PMID- 27551030 TI - CMA GC: Seniors' health comes first for most Canadians. PMID- 27551029 TI - The influence of habitat on the evolution of plants: a case study across Saxifragales. AB - BACKGROUND AND AIMS: Organismal evolution tends to be closely associated with ecological conditions. However, the extent to which this association constrains adaptation or diversification into new habitats remains unclear. We studied habitat evolution in the hyper-diverse angiosperm clade Saxifragales. METHODS: We used species-level phylogenies for approx. 950 species to analyse the evolution of habitat shifts as well as their influence on plant diversification. We combined habitat characterization based on floristic assignments and state-of-the art phylogenetic comparative methods to estimate within- and across-habitat diversification patterns. KEY RESULTS: Our analyses showed that Saxifragales diversified into multiple habitats from a forest-inhabiting ancestor and that this diversification is governed by relatively rare habitat shifts. Lineages are likely to stay within inferred ancestral ecological conditions. Adaptation to some habitat types (e.g. aquatic, desert) may be canalizing events that lineages do not escape. Although associations between increased diversification rates and shifts in habitat preferences are occasionally observed, extreme macroevolutionary rates are closely associated with specific habitats. Lineages occurring in shrubland, and especially tundra and rock cliffs, exhibit comparatively high diversification, whereas forest, grassland, desert and aquatic habitats are associated with low diversification. CONCLUSIONS: The likelihood of occupation of new habitats appears to be asymmetric. Shifts to aquatic and desert habitats may be canalizing events. Other habitats, such as tundra, might act as evolutionary sources, while forests provide the only habitat seemingly colonized easily by lineages originating elsewhere. However, habitat shifts are very rare, and any major environmental alteration is expected to have dramatic evolutionary consequences. PMID- 27551032 TI - Misconduct saga rattles bone scientists. PMID- 27551031 TI - Palliative care for chronic illness: driving change. PMID- 27551033 TI - Repetitive transcranial magnetic stimulation: an emerging treatment for medication-resistant depression. PMID- 27551035 TI - Mycobacterium marinum infection with sporotrichoid spread from fish tank exposure. PMID- 27551034 TI - Association between resting heart rate and coronary artery disease, stroke, sudden death and noncardiovascular diseases: a meta-analysis. AB - BACKGROUND: Resting heart rate is linked to risk of coronary artery disease, stroke, sudden death and noncardiovascular diseases. We conducted a meta-analysis to assess these associations in general populations and in populations of patients with hypertension or diabetes mellitus. METHODS: We searched PubMed, Embase and MEDLINE from inception to Mar. 5, 2016. We used a random-effects model to combine study-specific relative risks (RRs). We used restricted cubic splines to assess the dose-response relation. RESULTS: We included 45 nonrandomized prospective cohort studies in the meta-analysis. The multivariable adjusted RR with an increment of 10 beats/min in resting heart rate was 1.12 (95% confidence interval [CI] 1.09-1.14) for coronary artery disease, 1.05 (95% CI 1.01-1.08) for stroke, 1.12 (95% CI 1.02-1.24) for sudden death, 1.16 (95% CI 1.12-1.21) for noncardiovascular diseases, 1.09 (95% CI 1.06-1.12) for all types of cancer and 1.25 (95% CI 1.17-1.34) for noncardiovascular diseases excluding cancer. All of these relations were linear. In an analysis by category of resting heart rate (< 60 [reference], 60-70, 70-80 and > 80 beats/min), the RRs were 0.99 (95% CI 0.93 1.04), 1.08 (95% CI 1.01-1.16) and 1.30 (95% CI 1.19-1.43), respectively, for coronary artery disease; 1.08 (95% CI 0.98-1.19), 1.11 (95% CI 0.98-1.25) and 1.08 (95% CI 0.93-1.25), respectively, for stroke; and 1.17 (95% CI 0.94-1.46), 1.31 (95% CI 1.12-1.54) and 1.57 (95% CI 1.39-1.77), respectively, for noncardiovascular diseases. After excluding studies involving patients with hypertension or diabetes, we obtained similar results for coronary artery disease, stroke and noncardiovascular diseases, but found no association with sudden death. INTERPRETATION: Resting heart rate was an independent predictor of coronary artery disease, stroke, sudden death and noncardiovascular diseases over all of the studies combined. When the analysis included only studies concerning general populations, resting heart rate was not associated with sudden death. PMID- 27551036 TI - Protecting the plain packaging consultation from tobacco industry interference. PMID- 27551037 TI - Canada's high drug prices under review. PMID- 27551038 TI - The Chlamydia pneumoniae Adhesin Pmp21 Forms Oligomers with Adhesive Properties. AB - Chlamydiae sp. are obligate intracellular pathogens that cause a variety of diseases in humans. The adhesion of Chlamydiae to the eukaryotic host cell is a pivotal step in pathogenesis. The adhesin family of polymorphic membrane proteins (Pmp) in Chlamydia pneumoniae consists of 21 members. Pmp21 binds to the epidermal growth factor receptor (EGFR). Pmps contain large numbers of FXXN (where X is any amino acid) and GGA(I/L/V) motifs. At least two of these motifs are crucial for adhesion by certain Pmp21 fragments. Here we describe how the two FXXN motifs in Pmp21-D (D-Wt), a domain of Pmp21, influence its self-interaction, folding, and adhesive capacities. Refolded D-Wt molecules form oligomers with high sedimentation values (8-85 S). These oligomers take the form of elongated protofibrils, which exhibit Thioflavin T fluorescence, like the amyloid protein fragment beta42. A mutant version of Pmp21-D (D-Mt), with FXXN motifs replaced by SXXV, shows a markedly reduced capacity to form oligomers. Secondary-structure assays revealed that monomers of both variants exist predominantly as random coils, whereas the oligomers form predominantly beta-sheets. Adhesion studies revealed that oligomers of D-Wt (D-Wt-O) mediate significantly enhanced binding to human epithelial cells relative to D-Mt-O and monomeric protein species. Moreover, D-Wt-O binds EGFR more efficiently than D-Wt monomers. Importantly, pretreatment of human cells with D-Wt-O reduces infectivity upon subsequent challenge with C. pneumoniae more effectively than all other protein species. Hence, the FXXN motif in D-Wt induces the formation of beta-sheet-rich oligomeric protofibrils, which are important for adhesion to, and subsequent infection of human cells. PMID- 27551039 TI - Functional Characterization of UDP-apiose Synthases from Bryophytes and Green Algae Provides Insight into the Appearance of Apiose-containing Glycans during Plant Evolution. AB - Apiose is a branched monosaccharide that is present in the cell wall pectic polysaccharides rhamnogalacturonan II and apiogalacturonan and in numerous plant secondary metabolites. These apiose-containing glycans are synthesized using UDP apiose as the donor. UDP-apiose (UDP-Api) together with UDP-xylose is formed from UDP-glucuronic acid (UDP-GlcA) by UDP-Api synthase (UAS). It was hypothesized that the ability to form Api distinguishes vascular plants from the avascular plants and green algae. UAS from several dicotyledonous plants has been characterized; however, it is not known if avascular plants or green algae produce this enzyme. Here we report the identification and functional characterization of UAS homologs from avascular plants (mosses, liverwort, and hornwort), from streptophyte green algae, and from a monocot (duckweed). The recombinant UAS homologs all form UDP-Api from UDP-glucuronic acid albeit in different amounts. Apiose was detected in aqueous methanolic extracts of these plants. Apiose was detected in duckweed cell walls but not in the walls of the avascular plants and algae. Overexpressing duckweed UAS in the moss Physcomitrella patens led to an increase in the amounts of aqueous methanol acetonitrile-soluble apiose but did not result in discernible amounts of cell wall-associated apiose. Thus, bryophytes and algae likely lack the glycosyltransferase machinery required to synthesize apiose-containing cell wall glycans. Nevertheless, these plants may have the ability to form apiosylated secondary metabolites. Our data are the first to provide evidence that the ability to form apiose existed prior to the appearance of rhamnogalacturonan II and apiogalacturonan and provide new insights into the evolution of apiose containing glycans. PMID- 27551040 TI - Hepatitis C Virus Nonstructural 5A Protein Interacts with Abelson Interactor 1 and Modulates Epidermal Growth Factor-mediated MEK/ERK Signaling Pathway. AB - The propagation of hepatitis C virus (HCV) is highly dependent on host cellular factors. To identify the cellular factors involved in HCV propagation, we have previously performed protein microarray assays using the HCV nonstructural 5A (NS5A) protein as a probe. Of ~9,000 host proteins immobilized in a microarray, ~90 cellular proteins were identified as HCV NS5A interacting partners. Of these candidates, we selected Abelson interactor 1 (Abi1) for further characterization. Binding of HCV NS5A to Abi1 was verified by both in vitro pulldown and coimmunoprecipitation assays. HCV NS5A interacted with Abi1 through regions I + II of Abi1 and domain I of NS5A. We further demonstrated that Abi1 colocalized with the HCV NS5A protein in the cytoplasm. We showed that NS5A inhibited epidermal growth factor-mediated ERK and Egr1 activations and this inhibitory activity of NS5A was nullified in Abi1-knockdown cells. Moreover, silencing of Abi1 expression impaired HCV replication, whereas overexpression of Abi1 promoted HCV propagation. Collectively, these data indicate that HCV exploits host Abi1 protein via NS5A to modulate MEK/ERK signaling pathway for its own propagation. PMID- 27551041 TI - Mutations in TrkA Causing Congenital Insensitivity to Pain with Anhidrosis (CIPA) Induce Misfolding, Aggregation, and Mutation-dependent Neurodegeneration by Dysfunction of the Autophagic Flux. AB - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder characterized by insensitivity to noxious stimuli and variable intellectual disability (ID) due to mutations in the NTRK1 gene encoding the NGF receptor TrkA. To get an insight in the effect of NTRK1 mutations in the cognitive phenotype we biochemically characterized three TrkA mutations identified in children diagnosed of CIPA with variable ID. These mutations are located in different domains of the protein; L213P in the extracellular domain, Delta736 in the kinase domain, and C300stop in the extracellular domain, a new mutation causing CIPA diagnosed in a Spanish teenager. We found that TrkA mutations induce misfolding, retention in the endoplasmic reticulum (ER), and aggregation in a mutation-dependent manner. The distinct mutations are degraded with a different kinetics by different ER quality control mechanisms; although C300stop is rapidly disposed by autophagy, Delta736 degradation is sensitive to the proteasome and to autophagy inhibitors, and L213P is a long-lived protein refractory to degradation. In addition L213P enhances the formation of autophagic vesicles triggering an increase in the autophagic flux with deleterious consequences. Mouse cortical neurons expressing L213P showed the accumulation of LC3-GFP positive puncta and dystrophic neurites. Our data suggest that TrkA misfolding and aggregation induced by some CIPA mutations disrupt the autophagy homeostasis causing neurodegeneration. We propose that distinct disease-causing mutations of TrkA generate different levels of cell toxicity, which may provide an explanation of the variable intellectual disability observed in CIPA patients. PMID- 27551042 TI - Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE. AB - Renal cells of the thick ascending limb (TAL) reabsorb NaCl via the apical Na+/K+/2Cl- co-transporter NKCC2. Trafficking of NKCC2 to the apical surface regulates NKCC2-mediated NaCl absorption and blood pressure. The molecular mechanisms by which NKCC2 reaches the apical surface and their role in renal function and maintenance of blood pressure are poorly characterized. Here we report that NKCC2 interacts with the vesicle fusion protein VAMP3, and they co localize at the TAL apical surface. We observed that silencing VAMP3 in vivo blocks constitutive NKCC2 exocytic delivery, decreasing the amount of NKCC2 at the TAL apical surface. VAMP3 is not required for cAMP-stimulated NKCC2 exocytic delivery. Additionally, genetic deletion of VAMP3 in mice decreased total expression of NKCC2 in the TAL and lowered blood pressure. Consistent with these results, urinary excretion of water and electrolytes was higher in VAMP3 knock out mice, which produced more diluted urine. We conclude that VAMP3 interacts with NKCC2 and mediates its constitutive exocytic delivery to the apical surface. Additionally, VAMP3 is required for normal NKCC2 expression, renal function, and blood pressure. PMID- 27551043 TI - The Steroid Hormone 20-Hydroxyecdysone Promotes the Cytoplasmic Localization of Yorkie to Suppress Cell Proliferation and Induce Apoptosis. AB - The transcriptional co-activator Yki (Yorkie), a member of the Hippo pathway, regulates cell proliferation or apoptosis, depending on its nuclear or cytoplasmic location. However, the upstream factors regulating the subcellular localization of Yki are unclear. We found that the steroid hormone 20 hydroxyecdysone (20E) induces phosphorylation of Yki, causing it to remain in the cytoplasm, where it promotes apoptosis in the midgut of the lepidopteran insect Helicoverpa armigera Yki is expressed in various tissues, with an increase in the epidermis and midgut during early metamorphic molting. Yki is localized mainly in the nucleus of feeding larval midgut cells but is mainly localized in the cytoplasm of metamorphic molting larval midgut cells. The knockdown of Yki in the feeding larvae promotes larval-pupal transition, midgut programmed cell death, and repressed IAP1 (inhibitor of apoptosis 1) expression. Knockdown of Yki in the epidermal cell line (HaEpi) induced increased activation of Caspase3/7. Overexpressed Yki in HaEpi cells was mainly localized in the nucleus and induced cell proliferation. 20E promotes the cytoplasmic localization of Yki, reducing the expression of the IAP1, resulting in apoptosis. 20E promotes cytoplasmic retention of Yki by increasing Yki phosphorylation levels and promoting the interaction between Yki and the adaptor protein 14-3-3-epsilon. This regulation of Yki suppresses cell proliferation and induces cell apoptosis. PMID- 27551044 TI - Pseudouridine in the Anticodon of Escherichia coli tRNATyr(QPsiA) Is Catalyzed by the Dual Specificity Enzyme RluF. AB - Pseudouridine is found in almost all cellular ribonucleic acids (RNAs). Of the multiple characteristics attributed to pseudouridine, making messenger RNAs (mRNAs) highly translatable and non-immunogenic is one such feature that directly implicates this modification in protein synthesis. We report the existence of pseudouridine in the anticodon of Escherichia coli tyrosine transfer RNAs (tRNAs) at position 35. Pseudouridine was verified by multiple detection methods, which include pseudouridine-specific chemical derivatization and gas phase dissociation of RNA during liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of total tRNA isolated from E. coli pseudouridine synthase knock-out mutants identified RluF as the enzyme responsible for this modification. Furthermore, the absence of this modification compromises the translational ability of a luciferase reporter gene coding sequence when it is preceded by multiple tyrosine codons. This effect has implications for the translation of mRNAs that are rich in tyrosine codons in bacterial expression systems. PMID- 27551045 TI - Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction. AB - Recently, we have shown that high fat diet (HFD) in vivo and in vitro generates metabolic memory by altering H3K36me2 and H3K27me3 on the promoter of FOXO1 (transcription factor of gluconeogenic genes) (Kumar, S., Pamulapati, H., and Tikoo, K. (2016) Mol. Cell. Endocrinol. 422, 233-242). Here we checked the hypothesis whether concomitant diet reversal and metformin could overcome HFD induced metabolic memory and renal damage. Male adult Sprague-Dawley rats were rendered insulin-resistant by feeding high fat diet for 16 weeks. Then the rats were subjected to diet reversal alone and along with metformin for 8 weeks. Biochemical and histological markers of insulin resistance and kidney function were measured. Blood pressure and in vivo vascular reactivity to angiotensin II (200 ng kg-1) were also checked. Diet reversal could improve lipid profile but could not prevent renal complications induced by HFD. Interestingly, metformin along with diet reversal restored the levels of blood glucose, triglycerides, cholesterol, blood urea nitrogen, and creatinine. In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1beta) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3). Metformin was effective in lowering elevated basal blood pressure and acute change in mean arterial pressure in response to angiotensin II (Ang II). It also attenuated tubulointerstitial fibrosis and glomerulosclerosis induced by HFD feeding in kidney. Here we report, for the first time, that metformin treatment overcomes metabolic memory and prevents HFD-induced renal damage. PMID- 27551047 TI - Severe Molecular Defects Exhibited by the R179H Mutation in Human Vascular Smooth Muscle alpha-Actin. AB - Mutations in vascular smooth muscle alpha-actin (SM alpha-actin), encoded by ACTA2, are the most common cause of familial thoracic aortic aneurysms that lead to dissection (TAAD). The R179H mutation has a poor patient prognosis and is unique in causing multisystemic smooth muscle dysfunction (Milewicz, D. M., Ostergaard, J. R., Ala-Kokko, L. M., Khan, N., Grange, D. K., Mendoza-Londono, R., Bradley, T. J., Olney, A. H., Ades, L., Maher, J. F., Guo, D., Buja, L. M., Kim, D., Hyland, J. C., and Regalado, E. S. (2010) Am. J. Med. Genet. A 152A, 2437-2443). Here, we characterize this mutation in expressed human SM alpha actin. R179H actin shows severe polymerization defects, with a 40-fold higher critical concentration for assembly than WT SM alpha-actin, driven by a high disassembly rate. The mutant filaments are more readily severed by cofilin. Both defects are attenuated by copolymerization with WT. The R179H monomer binds more tightly to profilin, and formin binding suppresses nucleation and slows polymerization rates. Linear filaments will thus not be readily formed, and cells expressing R179H actin will likely have increased levels of monomeric G-actin. The cotranscription factor myocardin-related transcription factor-A, which affects cellular phenotype, binds R179H actin with less cooperativity than WT actin. Smooth muscle myosin moves R179H filaments more slowly than WT, even when copolymerized with equimolar amounts of WT. The marked decrease in the ability to form filaments may contribute to the poor patient prognosis and explain why R179H disrupts even visceral smooth muscle cell function where the SM alpha-actin isoform is present in low amounts. The R179H mutation has the potential to affect actin structure and function in both the contractile domain of the cell and the more dynamic cytoskeletal pool of actin, both of which are required for contraction. PMID- 27551046 TI - Composition and Activity of the Non-canonical Gram-positive SecY2 Complex. AB - The accessory Sec system in Streptococcus gordonii DL1 is a specialized export system that transports a large serine-rich repeat protein, Hsa, to the bacterial surface. The system is composed of core proteins SecA2 and SecY2 and accessory Sec proteins Asp1-Asp5. Similar to canonical SecYEG, SecY2 forms a channel for translocation of the Hsa adhesin across the cytoplasmic membrane. Accessory Sec proteins Asp4 and Asp5 have been suggested to work alongside SecY2 to form the translocon, similar to the associated SecY, SecE, and SecG of the canonical system (SecYEG). To test this theory, S. gordonii secY2, asp4, and asp5 were co expressed in Escherichia coli The resultant complex was subsequently purified, and its composition was confirmed by mass spectrometry to be SecY2-Asp4-Asp5. Like SecYEG, the non-canonical complex activates the ATPase activity of the SecA motor (SecA2). This study also shows that Asp4 and Asp5 are necessary for optimal adhesion of S. gordonii to glycoproteins gp340 and fibronectin, known Hsa binding partners, as well as for early stage biofilm formation. This work opens new avenues for understanding the structure and function of the accessory Sec system. PMID- 27551048 TI - MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression. AB - Serum glucocorticoids play a critical role in synchronizing circadian rhythm in peripheral tissues, and multiple mechanisms regulate tissue sensitivity to glucocorticoids. In the skeleton, circadian rhythm helps coordinate bone formation and resorption. Circadian rhythm is regulated through transcriptional and post-transcriptional feedback loops that include microRNAs. How microRNAs regulate circadian rhythm in bone is unexplored. We show that in mouse calvaria, miR-433 displays robust circadian rhythm, peaking just after dark. In C3H/10T1/2 cells synchronized with a pulse of dexamethasone, inhibition of miR-433 using a tough decoy altered the period and amplitude of Per2 gene expression, suggesting that miR-433 regulates rhythm. Although miR-433 does not directly target the Per2 3'-UTR, it does target two rhythmically expressed genes in calvaria, Igf1 and Hif1alpha. miR-433 can target the glucocorticoid receptor; however, glucocorticoid receptor protein abundance was unaffected in miR-433 decoy cells. Rather, miR-433 inhibition dramatically enhanced glucocorticoid signaling due to increased nuclear receptor translocation, activating glucocorticoid receptor transcriptional targets. Last, in calvaria of transgenic mice expressing a miR 433 decoy in osteoblastic cells (Col3.6 promoter), the amplitude of Per2 and Bmal1 mRNA rhythm was increased, confirming that miR-433 regulates circadian rhythm. miR-433 was previously shown to target Runx2, and mRNA for Runx2 and its downstream target, osteocalcin, were also increased in miR-433 decoy mouse calvaria. We hypothesize that miR-433 helps maintain circadian rhythm in osteoblasts by regulating sensitivity to glucocorticoid receptor signaling. PMID- 27551050 TI - Pulmonary sarcoidosis or post-immunotherapy granulomatous reaction induced by the anti-PD-1 monoclonal antibody pembrolizumab: the terminology is not the key point. PMID- 27551049 TI - DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes: A MECHANISM PROMOTING GLUCOCORTICOID INSENSITIVITY. AB - Although the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, mediates dexamethasone-induced repression of MAPKs, 14 of 46 interleukin-1beta (IL1B) induced mRNAs were significantly enhanced by DUSP1 overexpression in pulmonary A549 cells. These include the interferon regulatory factor, IRF1, and the chemokine, CXCL10. Of these, DUSP1-enhanced mRNAs, 10 including CXCL10, were IRF1 dependent. MAPK inhibitors and DUSP1 overexpression prolonged IRF1 expression by elevating transcription and increasing IRF1 mRNA and protein stability. Conversely, DUSP1 silencing increased IL1B-induced MAPK phosphorylation while significantly reducing IRF1 protein expression at 4 h. This confirms a regulatory network whereby DUSP1 switches off MAPKs to maintain IRF1 expression. There was no repression of IRF1 expression by dexamethasone in primary human bronchial epithelial cells, and in A549 cells IL1B-induced IRF1 protein was only modestly and transiently repressed. Although dexamethasone did not repress IL1B-induced IRF1 protein expression at 4-6 h, silencing of IL1B plus dexamethasone-induced DUSP1 significantly reduced IRF1 expression. IL1B-induced expression of CXCL10 was largely insensitive to dexamethasone, whereas other DUSP1-enhanced, IRF1 dependent mRNAs showed various degrees of repression. With IL1B plus dexamethasone, CXCL10 expression was also IRF1-dependent, and expression was reduced by DUSP1 silencing. Thus, IL1B plus dexamethasone-induced DUSP1 maintains expression of IRF1 and the IRF1-dependent gene, CXCL10. This is supported by chromatin immunoprecipitation showing IRF1 recruitment to be essentially unaffected by dexamethasone at the CXCL10 promoter or at the promoters of more highly repressed IRF1-dependent genes. Since IRF1-dependent genes, such as CXCL10, are central to host defense, these data may help explain the reduced effectiveness of glucocorticoids during asthma exacerbations. PMID- 27551051 TI - Is it best to expect the worst? Influence of patients' side-effect expectations on endocrine treatment outcome in a 2-year prospective clinical cohort study. AB - BACKGROUND: This study aims to determine the role of patient expectations as potentially modifiable factor of side-effects, quality of life, and adherence to endocrine treatment of breast cancer. PATIENTS AND METHODS: A 2-year prospective clinical cohort study was conducted in routine primary care with postoperative patients with hormone-receptor-positive breast cancer, scheduled to start adjuvant endocrine treatment. Structured patient-reported assessments of side effects, side-effect expectations, quality of life, and adherence took place during the first week post-surgery and after 3 and 24 months of endocrine treatment. RESULTS: Of 111 enrolled patients, at 3 and 24 months, 107 and 88 patients, respectively, were assessed. After 2 years of endocrine treatment, patients reported high rates of side-effects (arthralgia: 71.3%, weight gain: 53.4%, hot flashes: 46.5%), including symptoms not directly attributable to the medication (breathing problems: 28.1%, dizziness: 25.6%). Pre-treatment expectations significantly predicted patient-reported long-term side-effects and quality of life in multivariate models controlling for relevant medical and psychological variables. Relative risk of side-effects after 2 years of endocrine treatment was higher in patients with high negative expectations at baseline than in those with low negative expectations (RR = 1.833, CI 95%, 1.032-3.256). A significant interaction confirmed this expectation effect to be particularly evident in patients with high side-effects at 3 months. Furthermore, baseline expectations were associated with adherence at 24 months (r = -0.25, P = 0.006). CONCLUSIONS: Expectations are a genuine factor of clinical outcome from endocrine treatment for breast cancer. Negative expectations increase the risk of treatment specific side-effects, nocebo side-effects, and non-adherence. Yet, controlled studies are needed to analyze potential causal relationships. Optimizing individual expectations might be a promising strategy to improve side-effect burden, quality of life, and adherence during longer-term drug intake. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02088710. PMID- 27551052 TI - A20 inhibition of STAT1 expression in myeloid cells: a novel endogenous regulatory mechanism preventing development of enthesitis. AB - OBJECTIVES: A20 is an important endogenous regulator of inflammation. Single nucleotide polymorphisms in A20 have been associated with various immune-mediated inflammatory diseases, and cell-specific deletion of A20 results in diverse inflammatory phenotypes. Our goal was to delineate the underlying mechanisms of joint inflammation in myeloid-specific A20-deficient mice (A20myelKO mice). METHODS: Inflammation in A20myelKO mice was assessed in a time-dependent manner. Western blot analysis and quantitative PCR analysis were performed on bone marrow derived macrophages from A20myelKO and littermate control mice to study the effect of A20 on STAT1/STAT3 expression and STAT1/STAT3-dependent gene transcription in myeloid cells. The in vivo role of Janus kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signalling in the development of enthesitis in A20myelKO mice was assessed following administration of a JAK inhibitor versus placebo control. RESULTS: Enthesitis was found to be an early inflammatory lesion in A20myelKO mice. A20 negatively modulated STAT1 dependent, but generally not STAT3-dependent gene transcription in myeloid cells by suppressing STAT1 but not STAT3 expression, both in unstimulated conditions and after interferon-gamma or interleukin-6 stimulation. The increase in STAT1 gene transcription in the absence of A20 was shown to be JAK-STAT-dependent. Moreover, JAK inhibition in vivo resulted in significant reduction of enthesitis, both clinically and histopathologically. CONCLUSIONS: Our data reveal an important and novel interplay between myeloid cells and tissue resident cells at entheseal sites that is regulated by A20. In the absence of A20, STAT1 but not STAT3 expression is enhanced leading to STAT1-dependent inflammation. Therefore, A20 acts as a novel endogenous regulator of STAT1 that prevents onset of enthesitis. PMID- 27551053 TI - Eph-mediated tyrosine phosphorylation of citron kinase controls abscission. AB - Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-known local cell-to-cell communication pathway, in cell division. We show that activation of Eph signaling in vitro leads to multinucleation and polyploidy, and we demonstrate that this is caused by alteration of the ultimate step of cytokinesis, abscission. Control of abscission requires Eph kinase activity, and Src and citron kinase (CitK) are downstream effectors in the Eph-induced signal transduction cascade. CitK is phosphorylated on tyrosines in neural progenitors in vivo, and Src kinase directly phosphorylates CitK. We have identified the specific tyrosine residues of CitK that are phosphorylated and show that tyrosine phosphorylation of CitK impairs cytokinesis. Finally, we show that, similar to CitK, Ephrin/Eph signaling controls neuronal ploidy in the developing neocortex. Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis. PMID- 27551054 TI - A PP2A-B55 recognition signal controls substrate dephosphorylation kinetics during mitotic exit. AB - PP2A-B55 is one of the major phosphatases regulating cell division. Despite its importance for temporal control during mitotic exit, how B55 substrates are recognized and differentially dephosphorylated is unclear. Using phosphoproteomics combined with kinetic modeling to extract B55-dependent rate constants, we have systematically identified B55 substrates and assigned their temporal order in mitotic exit. These substrates share a bipartite polybasic recognition determinant (BPR) flanking a Cdk1 phosphorylation site. Experiments and modeling show that dephosphorylation rate is encoded into B55 substrates, including its inhibitor ENSA, by cooperative action of basic residues within the BPR. A complementary acidic surface on B55 decodes this signal, supporting a cooperative electrostatic mechanism for substrate selection. A further level of specificity is encoded into B55 substrates because B55 displays selectivity for phosphothreonine. These simple biochemical properties, combined with feedback control of B55 activity by the phosphoserine-containing substrate/inhibitor ENSA, can help explain the temporal sequence of events during exit from mitosis. PMID- 27551055 TI - Molecular mechanism of central nervous system repair by the Drosophila NG2 homologue kon-tiki. AB - Neuron glia antigen 2 (NG2)-positive glia are repair cells that proliferate upon central nervous system (CNS) damage, promoting functional recovery. However, repair is limited because of the failure of the newly produced glial cells to differentiate. It is a key goal to discover how to regulate NG2 to enable glial proliferation and differentiation conducive to repair. Drosophila has an NG2 homologue called kon-tiki (kon), of unknown CNS function. We show that kon promotes repair and identify the underlying mechanism. Crush injury up-regulates kon expression downstream of Notch. Kon in turn induces glial proliferation and initiates glial differentiation by activating glial genes and prospero (pros). Two negative feedback loops with Notch and Pros allow Kon to drive the homeostatic regulation required for repair. By modulating Kon levels in glia, we could prevent or promote CNS repair. Thus, the functional links between Kon, Notch, and Pros are essential for, and can drive, repair. Analogous mechanisms could promote CNS repair in mammals. PMID- 27551056 TI - Septins promote macropinosome maturation and traffic to the lysosome by facilitating membrane fusion. AB - Macropinocytosis, the internalization of extracellular fluid and material by plasma membrane ruffles, is critical for antigen presentation, cell metabolism, and signaling. Macropinosomes mature through homotypic and heterotypic fusion with endosomes and ultimately merge with lysosomes. The molecular underpinnings of this clathrin-independent endocytic pathway are largely unknown. Here, we show that the filamentous septin GTPases associate preferentially with maturing macropinosomes in a phosphatidylinositol 3,5-bisphosphate-dependent manner and localize to their contact/fusion sites with macropinosomes/endosomes. Septin knockdown results in large clusters of docked macropinosomes, which persist longer and exhibit fewer fusion events. Septin depletion and overexpression down regulates and enhances, respectively, the delivery of fluid-phase cargo to lysosomes, without affecting Rab5 and Rab7 recruitment to macropinosomes/endosomes. In vitro reconstitution assays show that fusion of macropinosomes/endosomes is abrogated by septin immunodepletion and function blocking antibodies and is induced by recombinant septins in the absence of cytosol and polymerized actin. Thus, septins regulate fluid-phase cargo traffic to lysosomes by promoting macropinosome maturation and fusion with endosomes/lysosomes. PMID- 27551057 TI - Mitotic exit: Determining the PP2A dephosphorylation program. AB - In mitotic exit, proteins that were highly phosphorylated are sequentially targeted by the phosphatase PP2A-B55, but what underlies substrate selection is unclear. In this issue, Cundell et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201606033) identify the determinants of PP2A-B55's dephosphorylation program, thereby influencing spindle disassembly, nuclear envelope reformation, and cytokinesis. PMID- 27551059 TI - Cycling Rho for tissue contraction. AB - Cell contractility, driven by the RhoA GTPase, is a fundamental determinant of tissue morphogenesis. In this issue, Mason et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201603077) reveal that cyclic inactivation of RhoA, mediated by its antagonist, C-GAP, is essential for effective contractility to occur. PMID- 27551058 TI - RhoA GTPase inhibition organizes contraction during epithelial morphogenesis. AB - During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding. PMID- 27551060 TI - CRISPR-Cas9 nuclear dynamics and target recognition in living cells. AB - The bacterial CRISPR-Cas9 system has been repurposed for genome engineering, transcription modulation, and chromosome imaging in eukaryotic cells. However, the nuclear dynamics of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) guide RNAs and target interrogation are not well defined in living cells. Here, we deployed a dual-color CRISPR system to directly measure the stability of both Cas9 and guide RNA. We found that Cas9 is essential for guide RNA stability and that the nuclear Cas9-guide RNA complex levels limit the targeting efficiency. Fluorescence recovery after photobleaching measurements revealed that single mismatches in the guide RNA seed sequence reduce the target residence time from >3 h to as low as <2 min in a nucleotide identity- and position-dependent manner. We further show that the duration of target residence correlates with cleavage activity. These results reveal that CRISPR discriminates between genuine versus mismatched targets for genome editing via radical alterations in residence time. PMID- 27551062 TI - Predictors of fever-related admissions to a paediatric assessment unit, ward and reattendances in a South London emergency department: the CABIN 2 study. AB - OBJECTIVE: To explore the risk factors for ward and paediatric assessment unit (PAU) admissions from the emergency department (ED). DESIGN: Prospective observational study. SETTING AND PATIENTS: Febrile children attending a large tertiary care ED during the winter of 2014-2015. MAIN OUTCOME MEASURES: Ward and PAU admissions, National Institute for Health and Care Excellence (NICE) guidelines classification, reattendance to the ED within 28 days and antibiotic use. RESULTS: A total of 1097 children attending the children's ED with fever were analysed. Risk factors for PAU admission were tachycardia (RR=1.1, 95% CI (1 to 1.1)), ill-appearance (RR=2.2, 95% CI (1.2 to 4.2)), abnormal chest findings (RR=2.1, 95% CI (1.2 to 4.3)), categorised as NICE amber (RR 1.7 95% CI (1.2 to 2.5)). There was a 30% discordance between NICE categorisation at triage and statistical internal validation. Predictors of ward admission were a systemic (RR=6.9, 95% CI (2.4 to 19.8)) or gastrointestinal illness (RR=3.8, 95% (1.4 to 10.4)) and categorised as NICE Red (RR=5.9, 95% CI (2.2 to 15.3)). Only 51 children had probable bacterial pneumonia (4.6%), 52 children had a proven urinary tract infection (4.2%), with just 2 (0.2%) positive blood cultures out of 485 (44%) children who received an antibiotic. 15% of all children reattended by 28 days and were more likely to have been categorised as Amber and had investigations on initial visit. CONCLUSIONS: Risk factors for PAU and ward admissions are different in this setting with high reattendance rates and very low proportion of confirmed/probable serious bacterial infections. Future studies need to focus on reducing avoidable admissions and antibiotic treatment. PMID- 27551063 TI - miRNA-miRNA crosstalk: from genomics to phenomics. AB - The discovery of microRNA (miRNA)-miRNA crosstalk has greatly improved our understanding of complex gene regulatory networks in normal and disease-specific physiological conditions. Numerous approaches have been proposed for modeling miRNA-miRNA networks based on genomic sequences, miRNA-mRNA regulation, functional information and phenomics alone, or by integrating heterogeneous data. In addition, it is expected that miRNA-miRNA crosstalk can be reprogrammed in different tissues or specific diseases. Thus, transcriptome data have also been integrated to construct context-specific miRNA-miRNA networks. In this review, we summarize the state-of-the-art miRNA-miRNA network modeling methods, which range from genomics to phenomics, where we focus on the need to integrate heterogeneous types of omics data. Finally, we suggest future directions for studies of crosstalk of noncoding RNAs. This comprehensive summarization and discussion elucidated in this work provide constructive insights into miRNA-miRNA crosstalk. PMID- 27551061 TI - Eye-tracking-based assessment of cognitive function in low-resource settings. AB - BACKGROUND: Early development of neurocognitive functions in infants can be compromised by poverty, malnutrition and lack of adequate stimulation. Optimal management of neurodevelopmental problems in infants requires assessment tools that can be used early in life, and are objective and applicable across economic, cultural and educational settings. OBJECTIVE AND DESIGN: The present study examined the feasibility of infrared eye tracking as a novel and highly automated technique for assessing visual-orienting and sequence-learning abilities as well as attention to facial expressions in young (9-month-old) infants. Techniques piloted in a high-resource laboratory setting in Finland (N=39) were subsequently field-tested in a community health centre in rural Malawi (N=40). RESULTS: Parents' perception of the acceptability of the method (Finland 95%, Malawi 92%) and percentages of infants completing the whole eye-tracking test (Finland 95%, Malawi 90%) were high, and percentages of valid test trials (Finland 69-85%, Malawi 68-73%) satisfactory at both sites. Test completion rates were slightly higher for eye tracking (90%) than traditional observational tests (87%) in Malawi. The predicted response pattern indicative of specific cognitive function was replicated in Malawi, but Malawian infants exhibited lower response rates and slower processing speed across tasks. CONCLUSIONS: High test completion rates and the replication of the predicted test patterns in a novel environment in Malawi support the feasibility of eye tracking as a technique for assessing infant development in low-resource setting. Further research is needed to the test retest stability and predictive validity of the eye-tracking scores in low-income settings. PMID- 27551065 TI - Nutrition mediates the expression of cultivar-farmer conflict in a fungus-growing ant. AB - Attine ants evolved farming 55-60 My before humans. Although evolutionarily derived leafcutter ants achieved industrial-scale farming, extant species from basal attine genera continue to farm loosely domesticated fungal cultivars capable of pursuing independent reproductive interests. We used feeding experiments with the basal attine Mycocepurus smithii to test whether reproductive allocation conflicts between farmers and cultivars constrain crop yield, possibly explaining why their mutualism has remained limited in scale and productivity. Stoichiometric and geometric framework approaches showed that carbohydrate-rich substrates maximize growth of both edible hyphae and inedible mushrooms, but that modest protein provisioning can suppress mushroom formation. Worker foraging was consistent with maximizing long-term cultivar performance: ant farmers could neither increase carbohydrate provisioning without cultivars allocating the excess toward mushroom production, nor increase protein provisioning without compromising somatic cultivar growth. Our results confirm that phylogenetically basal attine farming has been very successful over evolutionary time, but that unresolved host-symbiont conflict may have precluded these wild-type symbioses from rising to ecological dominance. That status was achieved by the evolutionarily derived leafcutter ants following full domestication of a coevolving cultivar 30-35 Mya after the first attine ants committed to farming. PMID- 27551066 TI - Correction for Chahal et al., Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. PMID- 27551064 TI - Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer. AB - Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1 Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors. PMID- 27551067 TI - QnAs with Huda Y. Zoghbi. PMID- 27551068 TI - Bioelectric impact of pathological angiogenesis on vascular function. AB - Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis. PMID- 27551069 TI - Power in everyday life. AB - How does power manifest itself in everyday life? Using experience-sampling methodology, we investigated the prevalence, sources, and correlates of power in people's natural environments. Participants experienced power-relevant situations regularly, though not frequently. High power was not restricted to a limited few: almost half of the sample reported experiencing high-power positions. Positional power and subjective feelings of power were strongly related but had unique relations with several individual difference measures and independent effects on participants' affect, cognition, and interpersonal relations. Subjective feelings of power resulted more from within-participant situational fluctuation, such as the social roles participants held at different times, than from stable differences between people. Our data supported some theoretical predictions about power's effects on affect, cognition, and interpersonal relations, but qualified others, particularly highlighting the role of responsibility in power's effects. Although the power literature has focused on high power, we found stronger effects of low power than high power. PMID- 27551070 TI - Structural basis for the CsrA-dependent modulation of translation initiation by an ancient regulatory protein. AB - Regulation of translation is critical for maintaining cellular protein levels, and thus protein homeostasis. The conserved RNA-binding protein CsrA (also called RsmA; for carbon storage regulator and regulator of secondary metabolism, respectively; hereafter called CsrA) represents a well-characterized example of regulation at the level of translation initiation in bacteria. Binding of a CsrA homodimer to the 5'UTR of an mRNA occludes the Shine-Dalgarno sequence, blocking ribosome access for translation. Small noncoding RNAs (sRNAs) can competitively antagonize CsrA activity by a well-understood mechanism. However, the regulation of CsrA by the protein FliW is just emerging. FliW antagonizes the CsrA-dependent repression of translation of the flagellar filament protein, flagellin. Crystal structures of the FliW monomer reveal a novel, minimal beta-barrel-like fold. Structural analysis of the CsrA/FliW heterotetramer shows that FliW interacts with a C-terminal extension of CsrA. In contrast to the competitive regulation of CsrA by sRNAs, FliW allosterically antagonizes CsrA in a noncompetitive manner by excluding the 5'UTR from the CsrA-RNA binding site. Our phylogenetic analysis shows that the FliW-mediated regulation of CsrA regulation is the ancestral state in flagellated bacteria. We thus demonstrate fundamental mechanistic differences in the regulation of CsrA by sRNA in comparison with an ancient regulatory protein. PMID- 27551071 TI - Precision glycocalyx editing as a strategy for cancer immunotherapy. AB - Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. Here, we report the development of antibody sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx. We chemically fused a recombinant sialidase to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab through a C terminal aldehyde tag. The antibody-sialidase conjugate desialylated tumor cells in a HER2-dependent manner, reduced binding by natural killer (NK) cell inhibitory sialic acid-binding Ig-like lectin (Siglec) receptors, and enhanced binding to the NK-activating receptor natural killer group 2D (NKG2D). Sialidase conjugation to trastuzumab enhanced ADCC against tumor cells expressing moderate levels of HER2, suggesting a therapeutic strategy for cancer patients with lower HER2 levels or inherent trastuzumab resistance. Precision glycocalyx editing with antibody-enzyme conjugates is therefore a promising avenue for cancer immune therapy. PMID- 27551073 TI - Correction for Boothby et al., Evidence for extensive horizontal gene transfer from the draft genome of a tardigrade. PMID- 27551072 TI - Autophagy and ubiquitin-proteasome system contribute to sperm mitophagy after mammalian fertilization. AB - Maternal inheritance of mitochondria and mtDNA is a universal principle in human and animal development, guided by selective ubiquitin-dependent degradation of the sperm-borne mitochondria after fertilization. However, it is not clear how the 26S proteasome, the ubiquitin-dependent protease that is only capable of degrading one protein molecule at a time, can dispose of a whole sperm mitochondrial sheath. We hypothesized that the canonical ubiquitin-like autophagy receptors [sequestosome 1 (SQSTM1), microtubule-associated protein 1 light chain 3 (LC3), gamma-aminobutyric acid receptor-associated protein (GABARAP)] and the nontraditional mitophagy pathways involving ubiquitin-proteasome system and the ubiquitin-binding protein dislocase, valosin-containing protein (VCP), may act in concert during mammalian sperm mitophagy. We found that the SQSTM1, but not GABARAP or LC3, associated with sperm mitochondria after fertilization in pig and rhesus monkey zygotes. Three sperm mitochondrial proteins copurified with the recombinant, ubiquitin-associated domain of SQSTM1. The accumulation of GABARAP containing protein aggregates was observed in the vicinity of sperm mitochondrial sheaths in the zygotes and increased in the embryos treated with proteasomal inhibitor MG132, in which intact sperm mitochondrial sheaths were observed. Pharmacological inhibition of VCP significantly delayed the process of sperm mitophagy and completely prevented it when combined with microinjection of autophagy-targeting antibodies specific to SQSTM1 and/or GABARAP. Sperm mitophagy in higher mammals thus relies on a combined action of SQSTM1-dependent autophagy and VCP-mediated dislocation and presentation of ubiquitinated sperm mitochondrial proteins to the 26S proteasome, explaining how the whole sperm mitochondria are degraded inside the fertilized mammalian oocytes by a protein recycling system involved in degradation of single protein molecules. PMID- 27551074 TI - Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS. AB - Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons in the brain and spinal cord. It has been suggested that the toxicity of mutant SOD1 results from its misfolding and accumulation on the cytoplasmic faces of intracellular organelles, including the mitochondria and endoplasmic reticulum (ER) of ALS-affected tissues. Recently, macrophage migration inhibitory factor (MIF) was shown to directly inhibit the accumulation of misfolded SOD1 and its binding to intracellular membranes, but the role of endogenous MIF in modulating SOD1 misfolding in vivo remains unknown. To elucidate this role, we bred MIF-deficient mice with SOD1(G85R) mice, which express a dismutase-inactive mutant of SOD1 and are considered a model of familial ALS. We found that the accumulation of misfolded SOD1, its association with mitochondrial and ER membranes, and the levels of sedimentable insoluble SOD1 aggregates were significantly higher in the spinal cords of SOD1(G85R)-MIF( /-) mice than in their SOD1(G85R)-MIF(+/+) littermates. Moreover, increasing MIF expression in neuronal cultures inhibited the accumulation of misfolded SOD1 and rescued from mutant SOD1-induced cell death. In contrast, the complete elimination of endogenous MIF accelerated disease onset and late disease progression and shortened the lifespan of the SOD1(G85R) mutant mice. These findings indicate that MIF plays a significant role in the folding and misfolding of SOD1 in vivo, and they have implications for the potential therapeutic role of up-regulating MIF within the nervous system to modulate the selective accumulation of misfolded SOD1. PMID- 27551075 TI - How chimpanzees cooperate in a competitive world. AB - Our species is routinely depicted as unique in its ability to achieve cooperation, whereas our closest relative, the chimpanzee (Pan troglodytes), is often characterized as overly competitive. Human cooperation is assisted by the cost attached to competitive tendencies through enforcement mechanisms, such as punishment and partner choice. To examine if chimpanzees possess the same ability to mitigate competition, we set up a cooperative task in the presence of the entire group of 11 adults, which required two or three individuals to pull jointly to receive rewards. This open-group set-up provided ample opportunity for competition (e.g., freeloading, displacements) and aggression. Despite this unique set-up and initial competitiveness, cooperation prevailed in the end, being at least five times as common as competition. The chimpanzees performed 3,565 cooperative acts while using a variety of enforcement mechanisms to overcome competition and freeloading, as measured by (attempted) thefts of rewards. These mechanisms included direct protest by the target, third-party punishment in which dominant individuals intervened against freeloaders, and partner choice. There was a marked difference between freeloading and displacement; freeloading tended to elicit withdrawal and third-party interventions, whereas displacements were met with a higher rate of direct retaliation. Humans have shown similar responses in controlled experiments, suggesting shared mechanisms across the primates to mitigate competition for the sake of cooperation. PMID- 27551076 TI - Paradoxical signaling regulates structural plasticity in dendritic spines. AB - Transient spine enlargement (3- to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics. PMID- 27551078 TI - Regional scattering of primate subplate. PMID- 27551077 TI - 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53 compromised cells. AB - The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53's oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1(MET)(APR-246). PK11007 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells. PMID- 27551080 TI - Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2. AB - Export of LDL-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein Niemann-Pick C1 (NPC1) and a soluble protein, Niemann Pick C2 (NPC2). Mutations in the genes encoding these proteins lead to Niemann Pick disease type C (NPC). NPC2 binds to NPC1's second (middle), lumenally oriented domain (MLD) and transfers cholesterol to NPC1's N-terminal domain (NTD). Here, we report the 2.4-A resolution crystal structure of a complex of human NPC1-MLD and NPC2 bearing bound cholesterol-3-O-sulfate. NPC1-MLD uses two protruding loops to bind NPC2, analogous to its interaction with the primed Ebola virus glycoprotein. Docking of the NPC1-NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and NTD cholesterol binding pockets, supporting the "hydrophobic hand-off" cholesterol transfer model. PMID- 27551079 TI - pH determines the energetic efficiency of the cyanobacterial CO2 concentrating mechanism. AB - Many carbon-fixing bacteria rely on a CO2 concentrating mechanism (CCM) to elevate the CO2 concentration around the carboxylating enzyme ribulose bisphosphate carboxylase/oxygenase (RuBisCO). The CCM is postulated to simultaneously enhance the rate of carboxylation and minimize oxygenation, a competitive reaction with O2 also catalyzed by RuBisCO. To achieve this effect, the CCM combines two features: active transport of inorganic carbon into the cell and colocalization of carbonic anhydrase and RuBisCO inside proteinaceous microcompartments called carboxysomes. Understanding the significance of the various CCM components requires reconciling biochemical intuition with a quantitative description of the system. To this end, we have developed a mathematical model of the CCM to analyze its energetic costs and the inherent intertwining of physiology and pH. We find that intracellular pH greatly affects the cost of inorganic carbon accumulation. At low pH the inorganic carbon pool contains more of the highly cell-permeable H2CO3, necessitating a substantial expenditure of energy on transport to maintain internal inorganic carbon levels. An intracellular pH ~8 reduces leakage, making the CCM significantly more energetically efficient. This pH prediction coincides well with our measurement of intracellular pH in a model cyanobacterium. We also demonstrate that CO2 retention in the carboxysome is necessary, whereas selective uptake of HCO3 (-) into the carboxysome would not appreciably enhance energetic efficiency. Altogether, integration of pH produces a model that is quantitatively consistent with cyanobacterial physiology, emphasizing that pH cannot be neglected when describing biological systems interacting with inorganic carbon pools. PMID- 27551081 TI - Biophysical insight into mechanisms of sonoporation. AB - This study presents a unique approach to understanding the biophysical mechanisms of ultrasound-triggered cell membrane disruption (i.e., sonoporation). We report direct correlations between ultrasound-stimulated encapsulated microbubble oscillation physics and the resulting cellular membrane permeability by simultaneous microscopy of these two processes over their intrinsic physical timescales (microseconds for microbubble dynamics and seconds to minutes for local macromolecule uptake and cell membrane reorganization). We show that there exists a microbubble oscillation-induced shear-stress threshold, on the order of kilopascals, beyond which endothelial cellular membrane permeability increases. The shear-stress threshold exhibits an inverse square-root relation to the number of oscillation cycles and an approximately linear dependence on ultrasound frequency from 0.5 to 2 MHz. Further, via real-time 3D confocal microscopy measurements, our data provide evidence that a sonoporation event directly results in the immediate generation of membrane pores through both apical and basal cell membrane layers that reseal along their lateral area (resealing time of ~<2 min). Finally, we demonstrate the potential for sonoporation to indirectly initiate prolonged, intercellular gaps between adjacent, confluent cells (~>30-60 min). This real-time microscopic approach has provided insight into both the physical, cavitation-based mechanisms of sonoporation and the biophysical, cell membrane-based mechanisms by which microbubble acoustic behaviors cause acute and sustained enhancement of cellular and vascular permeability. PMID- 27551082 TI - Changes in active site histidine hydrogen bonding trigger cryptochrome activation. AB - Cryptochrome (CRY) is the principal light sensor of the insect circadian clock. Photoreduction of the Drosophila CRY (dCRY) flavin cofactor to the anionic semiquinone (ASQ) restructures a C-terminal tail helix (CTT) that otherwise inhibits interactions with targets that include the clock protein Timeless (TIM). All-atom molecular dynamics (MD) simulations indicate that flavin reduction destabilizes the CTT, which undergoes large-scale conformational changes (the CTT release) on short (25 ns) timescales. The CTT release correlates with the conformation and protonation state of conserved His378, which resides between the CTT and the flavin cofactor. Poisson-Boltzmann calculations indicate that flavin reduction substantially increases the His378 pKa Consistent with coupling between ASQ formation and His378 protonation, dCRY displays reduced photoreduction rates with increasing pH; however, His378Asn/Arg variants show no such pH dependence. Replica-exchange MD simulations also support CTT release mediated by changes in His378 hydrogen bonding and verify other responsive regions of the protein previously identified by proteolytic sensitivity assays. His378 dCRY variants show varying abilities to light-activate TIM and undergo self-degradation in cellular assays. Surprisingly, His378Arg/Lys variants do not degrade in light despite maintaining reactivity toward TIM, thereby implicating different conformational responses in these two functions. Thus, the dCRY photosensory mechanism involves flavin photoreduction coupled to protonation of His378, whose perturbed hydrogen-bonding pattern alters the CTT and surrounding regions. PMID- 27551083 TI - Caspase-1 clipping causes complications for alpha-synuclein. PMID- 27551084 TI - Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans. AB - Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal beta-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these beta-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state. PMID- 27551085 TI - Using the shortwave infrared to image middle ear pathologies. AB - Visualizing structures deep inside opaque biological tissues is one of the central challenges in biomedical imaging. Optical imaging with visible light provides high resolution and sensitivity; however, scattering and absorption of light by tissue limits the imaging depth to superficial features. Imaging with shortwave infrared light (SWIR, 1-2 MUm) shares many advantages of visible imaging, but light scattering in tissue is reduced, providing sufficient optical penetration depth to noninvasively interrogate subsurface tissue features. However, the clinical potential of this approach has been largely unexplored because suitable detectors, until recently, have been either unavailable or cost prohibitive. Here, taking advantage of newly available detector technology, we demonstrate the potential of SWIR light to improve diagnostics through the development of a medical otoscope for determining middle ear pathologies. We show that SWIR otoscopy has the potential to provide valuable diagnostic information complementary to that provided by visible pneumotoscopy. We show that in healthy adult human ears, deeper tissue penetration of SWIR light allows better visualization of middle ear structures through the tympanic membrane, including the ossicular chain, promontory, round window niche, and chorda tympani. In addition, we investigate the potential for detection of middle ear fluid, which has significant implications for diagnosing otitis media, the overdiagnosis of which is a primary factor in increased antibiotic resistance. Middle ear fluid shows strong light absorption between 1,400 and 1,550 nm, enabling straightforward fluid detection in a model using the SWIR otoscope. Moreover, our device is easily translatable to the clinic, as the ergonomics, visual output, and operation are similar to a conventional otoscope. PMID- 27551086 TI - Direct observation of aqueous secondary organic aerosol from biomass-burning emissions. AB - The mechanisms leading to the formation of secondary organic aerosol (SOA) are an important subject of ongoing research for both air quality and climate. Recent laboratory experiments suggest that reactions taking place in the atmospheric liquid phase represent a potentially significant source of SOA mass. Here, we report direct ambient observations of SOA mass formation from processing of biomass-burning emissions in the aqueous phase. Aqueous SOA (aqSOA) formation is observed both in fog water and in wet aerosol. The aqSOA from biomass burning contributes to the "brown" carbon (BrC) budget and exhibits light absorption wavelength dependence close to the upper bound of the values observed in laboratory experiments for fresh and processed biomass-burning emissions. We estimate that the aqSOA from residential wood combustion can account for up to 0.1-0.5 Tg of organic aerosol (OA) per y in Europe, equivalent to 4-20% of the total OA emissions. Our findings highlight the importance of aqSOA from anthropogenic emissions on air quality and climate. PMID- 27551087 TI - Semantic representations in the temporal pole predict false memories. AB - Recent advances in neuroscience have given us unprecedented insight into the neural mechanisms of false memory, showing that artificial memories can be inserted into the memory cells of the hippocampus in a way that is indistinguishable from true memories. However, this alone is not enough to explain how false memories can arise naturally in the course of our daily lives. Cognitive psychology has demonstrated that many instances of false memory, both in the laboratory and the real world, can be attributed to semantic interference. Whereas previous studies have found that a diverse set of regions show some involvement in semantic false memory, none have revealed the nature of the semantic representations underpinning the phenomenon. Here we use fMRI with representational similarity analysis to search for a neural code consistent with semantic false memory. We find clear evidence that false memories emerge from a similarity-based neural code in the temporal pole, a region that has been called the "semantic hub" of the brain. We further show that each individual has a partially unique semantic code within the temporal pole, and this unique code can predict idiosyncratic patterns of memory errors. Finally, we show that the same neural code can also predict variation in true-memory performance, consistent with an adaptive perspective on false memory. Taken together, our findings reveal the underlying structure of neural representations of semantic knowledge, and how this semantic structure can both enhance and distort our memories. PMID- 27551088 TI - Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding. AB - The pathogenesis of Klebsiella pneumonia is linked to the bacteria's ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K pneumonia biofilm development, and the expression of the genes encoding these proteins is activated by a 3',5'-cyclic diguanylic acid (c-di-GMP) regulated transcription factor, MrkH. To gain insight into MrkH function, we performed structural and biochemical analyses. Data revealed MrkH to be a monomer with a two-domain architecture consisting of a PilZ C-domain connected to an N domain that unexpectedly also harbors a PilZ-like fold. Comparison of apo- and c di-GMP-bound MrkH structures reveals a large 138 degrees interdomain rotation that is induced by binding an intercalated c-di-GMP dimer. c-di-GMP interacts with PilZ C-domain motifs 1 and 2 (RxxxR and D/NxSxxG) and a newly described c-di GMP-binding motif in the MrkH N domain. Strikingly, these c-di-GMP-binding motifs also stabilize an open state conformation in apo MrkH via contacts from the PilZ motif 1 to residues in the C-domain motif 2 and the c-di-GMP-binding N-domain motif. Use of the same regions in apo structure stabilization and c-di-GMP interaction allows distinction between the states. Indeed, domain reorientation by c-di-GMP complexation with MrkH, which leads to a highly compacted structure, suggests a mechanism by which the protein is activated to bind DNA. To our knowledge, MrkH represents the first instance of specific DNA binding mediated by PilZ domains. The MrkH structures also pave the way for the rational design of inhibitors that target K pneumonia biofilm formation. PMID- 27551089 TI - Climate-driven ground-level ozone extreme in the fall over the Southeast United States. AB - Ground-level ozone is adverse to human and vegetation health. High ground-level ozone concentrations usually occur over the United States in the summer, often referred to as the ozone season. However, observed monthly mean ozone concentrations in the southeastern United States were higher in October than July in 2010. The October ozone average in 2010 reached that of July in the past three decades (1980-2010). Our analysis shows that this extreme October ozone in 2010 over the Southeast is due in part to a dry and warm weather condition, which enhances photochemical production, air stagnation, and fire emissions. Observational evidence and modeling analysis also indicate that another significant contributor is enhanced emissions of biogenic isoprene, a major ozone precursor, from water-stressed plants under a dry and warm condition. The latter finding is corroborated by recent laboratory and field studies. This climate induced biogenic control also explains the puzzling fact that the two extremes of high October ozone both occurred in the 2000s when anthropogenic emissions were lower than the 1980s and 1990s, in contrast to the observed decreasing trend of July ozone in the region. The occurrences of a drying and warming fall, projected by climate models, will likely lead to more active photochemistry, enhanced biogenic isoprene and fire emissions, an extension of the ozone season from summer to fall, and an increase of secondary organic aerosols in the Southeast, posing challenges to regional air quality management. PMID- 27551090 TI - Light-driven carbon dioxide reduction to methane by nitrogenase in a photosynthetic bacterium. AB - Nitrogenase is an ATP-requiring enzyme capable of carrying out multielectron reductions of inert molecules. A purified remodeled nitrogenase containing two amino acid substitutions near the site of its FeMo cofactor was recently described as having the capacity to reduce carbon dioxide (CO2) to methane (CH4). Here, we developed the anoxygenic phototroph, Rhodopseudomonas palustris, as a biocatalyst capable of light-driven CO2 reduction to CH4 in vivo using this remodeled nitrogenase. Conversion of CO2 to CH4 by R. palustris required constitutive expression of nitrogenase, which was achieved by using a variant of the transcription factor NifA that is able to activate expression of nitrogenase under all growth conditions. Also, light was required for generation of ATP by cyclic photophosphorylation. CH4 production by R. palustris could be controlled by manipulating the distribution of electrons and energy available to nitrogenase. This work shows the feasibility of using microbes to generate hydrocarbons from CO2 in one enzymatic step using light energy. PMID- 27551091 TI - TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats. AB - The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24*Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins. The affinity for Sec23 is concentrated in the proline-rich domains (PRDs) of TANGO1 and cTAGE5, but Sec23 recognizes merely a PPP motif. The PRDs contain repeated PPP motifs separated by proline-rich linkers, so a single TANGO1/cTAGE5 receptor can bind multiple copies of coat protein in a close-packed array. We propose that TANGO1/cTAGE5 promotes the accretion of inner coat proteins to the helical lattice. Furthermore, we show that PPP motifs in the outer coat protein Sec31 also bind to Sec23, suggesting that stepwise COPII coat assembly will ultimately displace TANGO1/cTAGE5 and compartmentalize its operation to the base of the growing COPII tubule. PMID- 27551093 TI - Correction for AbouHaidar et al., Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt. PMID- 27551092 TI - Regulatory network analysis reveals novel regulators of seed desiccation tolerance in Arabidopsis thaliana. AB - Desiccation tolerance (DT) is a remarkable process that allows seeds in the dry state to remain viable for long periods of time that in some instances exceed 1,000 y. It has been postulated that seed DT evolved by rewiring the regulatory and signaling networks that controlled vegetative DT, which itself emerged as a crucial adaptive trait of early land plants. Understanding the networks that regulate seed desiccation tolerance in model plant systems would provide the tools to understand an evolutionary process that played a crucial role in the diversification of flowering plants. In this work, we used an integrated approach that included genomics, bioinformatics, metabolomics, and molecular genetics to identify and validate molecular networks that control the acquisition of DT in Arabidopsis seeds. Two DT-specific transcriptional subnetworks were identified related to storage of reserve compounds and cellular protection mechanisms that act downstream of the embryo development master regulators LEAFY COTYLEDON 1 and 2, FUSCA 3, and ABSCICIC ACID INSENSITIVE 3. Among the transcription factors identified as major nodes in the DT regulatory subnetworks, PLATZ1, PLATZ2, and AGL67 were confirmed by knockout mutants and overexpression in a desiccation intolerant mutant background to play an important role in seed DT. Additionally, we found that constitutive expression of PLATZ1 in WT plants confers partial DT in vegetative tissues. PMID- 27551094 TI - Self-regulation via neural simulation. AB - Can taking the perspective of other people modify our own affective responses to stimuli? To address this question, we examined the neurobiological mechanisms supporting the ability to take another person's perspective and thereby emotionally experience the world as they would. We measured participants' neural activity as they attempted to predict the emotional responses of two individuals that differed in terms of their proneness to experience negative affect. Results showed that behavioral and neural signatures of negative affect (amygdala activity and a distributed multivoxel pattern reflecting affective negativity) simulated the presumed affective state of the target person. Furthermore, the anterior medial prefrontal cortex (mPFC)-a region implicated in mental state inference-exhibited a perspective-dependent pattern of connectivity with the amygdala, and the multivoxel pattern of activity within the mPFC differentiated between the two targets. We discuss the implications of these findings for research on perspective-taking and self-regulation. PMID- 27551095 TI - Bird assemblage vulnerability depends on the diversity and biogeographic histories of islands. AB - Biodiversity is widely acknowledged to influence the magnitude and stability of a large array of ecosystem properties, with biodiverse systems thought to be more functionally robust. As such, diverse systems may be safer harbors for vulnerable species, resulting in a positive association between biodiversity and the collective vulnerability of species in an assemblage, or "assemblage vulnerability." We find that, for 35 islands across Northern Melanesia, bird assemblage vulnerability and biodiversity are positively associated. This relationship is highly contingent on Pleistocene connectivity, suggesting that biogeographic history-a factor often overlooked in biodiversity and ecosystem functioning studies-may influence contemporary ecological processes. In the face of biodiversity loss attributable to anthropogenic drivers, reduced ecosystem functioning may erode the safe harbors of vulnerable assemblages. Paradoxically, these results suggest that biodiverse systems, as more robust systems, may experience greater biodiversity loss over ecological time because they harbor more vulnerable species accumulated over evolutionary time. PMID- 27551096 TI - NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics. AB - Natural killer (NK) cells are known to be activated by Th1-type cytokines, such as IL-2, -12, or -18, and they secrete a large amount of IFN-gamma that accelerates Th1-type responses. However, the roles of NK cells in Th2-type responses have remained unclear. Because IL-4 acts as an initiator of Th2-type responses, we examined the characteristics of NK cells in mice overexpressing IL 4. In this study, we report that IL-4 overexpression induces distinctive characteristics of NK cells (B220(high)/CD11b(low)/IL-18Ralpha(low)), which are different from mature conventional NK (cNK) cells (B220(low)/CD11b(high)/IL 18Ralpha(high)). IL-4 overexpression induces proliferation of tissue-resident macrophages, which contributes to NK cell proliferation via production of IL-15. These IL-4-induced NK cells (IL4-NK cells) produce higher levels of IFN-gamma, IL 10, and GM-CSF, and exhibit high cytotoxicity compared with cNK cells. Furthermore, incubation of cNK cells with IL-15 and IL-4 alters their phenotype to that similar to IL4-NK cells. Finally, parasitic infection, which typically causes strong Th2-type responses, induces the development of NK cells with characteristics similar to IL4-NK cells. These IL4-NK-like cells do not develop in IL-4Ralpha KO mice by parasitic infection. Collectively, these results suggest a novel role of IL-4 in immune responses through the induction of the unique NK cells. PMID- 27551097 TI - Disulfide cross-linking influences symbiotic activities of nodule peptide NCR247. AB - Interactions of rhizobia with legumes establish the chronic intracellular infection that underlies symbiosis. Within nodules of inverted repeat-lacking clade (IRLC) legumes, rhizobia differentiate into nitrogen-fixing bacteroids. This terminal differentiation is driven by host nodule-specific cysteine-rich (NCR) peptides that orchestrate the adaptation of free-living bacteria into intracellular residents. Medicago truncatula encodes a family of >700 NCR peptides that have conserved cysteine motifs. NCR247 is a cationic peptide with four cysteines that can form two intramolecular disulfide bonds in the oxidized forms. This peptide affects Sinorhizobium meliloti transcription, translation, and cell division at low concentrations and is antimicrobial at higher concentrations. By preparing the three possible disulfide-cross-linked NCR247 regioisomers, the reduced peptide, and a variant lacking cysteines, we performed a systematic study of the effects of intramolecular disulfide cross-linking and cysteines on the activities of an NCR peptide. The relative activities of the five NCR247 variants differed strikingly among the various bioassays, suggesting that the NCR peptide-based language used by plants to control the development of their bacterial partners during symbiosis is even greater than previously recognized. These patterns indicate that certain NCR bioactivities require cysteines whereas others do not. The results also suggest that NCR247 may exert some of its effects within the cell envelope whereas other activities occur in the cytoplasm. BacA, a membrane protein that is critical for symbiosis, provides protection against all bactericidal forms of NCR247. Oxidative folding protects NCR247 from degradation by the symbiotically relevant metalloprotease HrrP (host range restriction peptidase), suggesting that disulfide bond formation may additionally stabilize NCR peptides during symbiosis. PMID- 27551098 TI - Stepwise metamorphosis of the tubeworm Hydroides elegans is mediated by a bacterial inducer and MAPK signaling. AB - Diverse animal taxa metamorphose between larval and juvenile phases in response to bacteria. Although bacteria-induced metamorphosis is widespread among metazoans, little is known about the molecular changes that occur in the animal upon stimulation by bacteria. Larvae of the tubeworm Hydroides elegans metamorphose in response to surface-bound Pseudoalteromonas luteoviolacea bacteria, producing ordered arrays of phage tail-like metamorphosis-associated contractile structures (MACs). Sequencing the Hydroides genome and transcripts during five developmental stages revealed that MACs induce the regulation of groups of genes important for tissue remodeling, innate immunity, and mitogen activated protein kinase (MAPK) signaling. Using two MAC mutations that block P. luteoviolacea from inducing settlement or metamorphosis and three MAPK inhibitors, we established a sequence of bacteria-induced metamorphic events: MACs induce larval settlement; then, particular properties of MACs encoded by a specific locus in P. luteoviolacea initiate cilia loss and activate metamorphosis associated transcription; finally, signaling through p38 and c-Jun N-terminal kinase (JNK) MAPK pathways alters gene expression and leads to morphological changes upon initiation of metamorphosis. Our results reveal that the intricate interaction between Hydroides and P. luteoviolacea can be dissected using genomic, genetic, and pharmacological tools. Hydroides' dependency on bacteria for metamorphosis highlights the importance of external stimuli to orchestrate animal development. The conservation of Hydroides genome content with distantly related deuterostomes (urchins, sea squirts, and humans) suggests that mechanisms of bacteria-induced metamorphosis in Hydroides may have conserved features in diverse animals. As a major biofouling agent, insight into the triggers of Hydroides metamorphosis might lead to practical strategies for fouling control. PMID- 27551099 TI - Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus. AB - Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF-PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF-PC LTD was observed. We reexamined slices obtained from these GluA2 K882A and GluA2 Delta7 knockin mutants at 3-6 mo of age. The conventional protocols of stimulation did not induce LTD in these mutant mice, as previously reported, but surprisingly, LTD was induced using certain modified protocols. Such modifications involved increases in the number of PF stimulation (from one to two or five), replacement of climbing fiber stimulation with somatic depolarization (50 ms), filling a patch pipette with a Cs(+)-based solution, or extension of the duration of conjunction. We also found that intracellular infusion of a selective PKCalpha inhibitor (Go6976) blocked LTD induction in the mutants, as in WT, suggesting that functional compensation occurred downstream of PKCalpha. The possibility that LTD in the mutants was caused by changes in membrane resistance, access resistance, or presynaptic property was excluded. The present results demonstrate that LTD is inducible by intensified conjunctive stimulations even in K882A and Delta7 mutants, indicating no contradiction against the LTD hypothesis of motor learning. PMID- 27551100 TI - Emergence of ion channel modal gating from independent subunit kinetics. AB - Many ion channels exhibit a slow stochastic switching between distinct modes of gating activity. This feature of channel behavior has pronounced implications for the dynamics of ionic currents and the signaling pathways that they regulate. A canonical example is the inositol 1,4,5-trisphosphate receptor (IP3R) channel, whose regulation of intracellular Ca(2+) concentration is essential for numerous cellular processes. However, the underlying biophysical mechanisms that give rise to modal gating in this and most other channels remain unknown. Although ion channels are composed of protein subunits, previous mathematical models of modal gating are coarse grained at the level of whole-channel states, limiting further dialogue between theory and experiment. Here we propose an origin for modal gating, by modeling the kinetics of ligand binding and conformational change in the IP3R at the subunit level. We find good agreement with experimental data over a wide range of ligand concentrations, accounting for equilibrium channel properties, transient responses to changing ligand conditions, and modal gating statistics. We show how this can be understood within a simple analytical framework and confirm our results with stochastic simulations. The model assumes that channel subunits are independent, demonstrating that cooperative binding or concerted conformational changes are not required for modal gating. Moreover, the model embodies a generally applicable principle: If a timescale separation exists in the kinetics of individual subunits, then modal gating can arise as an emergent property of channel behavior. PMID- 27551101 TI - Sandwich-structured polymer nanocomposites with high energy density and great charge-discharge efficiency at elevated temperatures. AB - The demand for a new generation of high-temperature dielectric materials toward capacitive energy storage has been driven by the rise of high-power applications such as electric vehicles, aircraft, and pulsed power systems where the power electronics are exposed to elevated temperatures. Polymer dielectrics are characterized by being lightweight, and their scalability, mechanical flexibility, high dielectric strength, and great reliability, but they are limited to relatively low operating temperatures. The existing polymer nanocomposite-based dielectrics with a limited energy density at high temperatures also present a major barrier to achieving significant reductions in size and weight of energy devices. Here we report the sandwich structures as an efficient route to high-temperature dielectric polymer nanocomposites that simultaneously possess high dielectric constant and low dielectric loss. In contrast to the conventional single-layer configuration, the rationally designed sandwich-structured polymer nanocomposites are capable of integrating the complementary properties of spatially organized multicomponents in a synergistic fashion to raise dielectric constant, and subsequently greatly improve discharged energy densities while retaining low loss and high charge-discharge efficiency at elevated temperatures. At 150 degrees C and 200 MV m(-1), an operating condition toward electric vehicle applications, the sandwich-structured polymer nanocomposites outperform the state-of-the-art polymer-based dielectrics in terms of energy density, power density, charge-discharge efficiency, and cyclability. The excellent dielectric and capacitive properties of the polymer nanocomposites may pave a way for widespread applications in modern electronics and power modules where harsh operating conditions are present. PMID- 27551102 TI - Reply to Smith: Electrorheological technology reduces the chocolate viscosity and fat level. PMID- 27551103 TI - Electrorheology and classical processing as routes to produce chocolate. PMID- 27551104 TI - Predicting the errors of predicted local backbone angles and non-local solvent- accessibilities of proteins by deep neural networks. AB - MOTIVATION: Backbone structures and solvent accessible surface area of proteins are benefited from continuous real value prediction because it removes the arbitrariness of defining boundary between different secondary-structure and solvent-accessibility states. However, lacking the confidence score for predicted values has limited their applications. Here we investigated whether or not we can make a reasonable prediction of absolute errors for predicted backbone torsion angles, Calpha-atom-based angles and torsion angles, solvent accessibility, contact numbers and half-sphere exposures by employing deep neural networks. RESULTS: We found that angle-based errors can be predicted most accurately with Spearman correlation coefficient (SPC) between predicted and actual errors at about 0.6. This is followed by solvent accessibility (SPC~0.5). The errors on contact-based structural properties are most difficult to predict (SPC between 0.2 and 0.3). We showed that predicted errors are significantly better error indicators than the average errors based on secondary-structure and amino-acid residue types. We further demonstrated the usefulness of predicted errors in model quality assessment. These error or confidence indictors are expected to be useful for prediction, assessment, and refinement of protein structures. AVAILABILITY AND IMPLEMENTATION: The method is available at http://sparks-lab.org as a part of SPIDER2 package. CONTACT: yuedong.yang@griffith.edu.au or yaoqi.zhou@griffith.edu.auSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27551105 TI - Integrating genomic information with protein sequence and 3D atomic level structure at the RCSB protein data bank. AB - : The Protein Data Bank (PDB) now contains more than 120,000 three-dimensional (3D) structures of biological macromolecules. To allow an interpretation of how PDB data relates to other publicly available annotations, we developed a novel data integration platform that maps 3D structural information across various datasets. This integration bridges from the human genome across protein sequence to 3D structure space. We developed novel software solutions for data management and visualization, while incorporating new libraries for web-based visualization using SVG graphics. AVAILABILITY AND IMPLEMENTATION: The new views are available from http://www.rcsb.org and software is available from https://github.com/rcsb/. CONTACT: andreas.prlic@rcsb.orgSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27551106 TI - PPI4DOCK: large scale assessment of the use of homology models in free docking over more than 1000 realistic targets. AB - MOTIVATION: Protein-protein docking methods are of great importance for understanding interactomes at the structural level. It has become increasingly appealing to use not only experimental structures but also homology models of unbound subunits as input for docking simulations. So far we are missing a large scale assessment of the success of rigid-body free docking methods on homology models. RESULTS: We explored how we could benefit from comparative modelling of unbound subunits to expand docking benchmark datasets. Starting from a collection of 3157 non-redundant, high X-ray resolution heterodimers, we developed the PPI4DOCK benchmark containing 1417 docking targets based on unbound homology models. Rigid-body docking by Zdock showed that for 1208 cases (85.2%), at least one correct decoy was generated, emphasizing the efficiency of rigid-body docking in generating correct assemblies. Overall, the PPI4DOCK benchmark contains a large set of realistic cases and provides new ground for assessing docking and scoring methodologies. AVAILABILITY AND IMPLEMENTATION: Benchmark sets can be downloaded from http://biodev.cea.fr/interevol/ppi4dock/ CONTACT: guerois@cea.frSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27551107 TI - Non-covalent forces tune the electron transfer complex between ferredoxin and sulfite reductase to optimize enzymatic activity. AB - Although electrostatic interactions between negatively charged ferredoxin (Fd) and positively charged sulfite reductase (SiR) have been predominantly highlighted to characterize complex formation, the detailed nature of intermolecular forces remains to be fully elucidated. We investigated interprotein forces for the formation of an electron transfer complex between Fd and SiR and their relationship to SiR activity using various approaches over NaCl concentrations between 0 and 400 mM. Fd-dependent SiR activity assays revealed a bell-shaped activity curve with a maximum ~40-70 mM NaCl and a reverse bell shaped dependence of interprotein affinity. Meanwhile, intrinsic SiR activity, as measured in a methyl viologen-dependent assay, exhibited saturation above 100 mM NaCl. Thus, two assays suggested that interprotein interaction is crucial in controlling Fd-dependent SiR activity. Calorimetric analyses showed the monotonic decrease in interprotein affinity on increasing NaCl concentrations, distinguished from a reverse bell-shaped interprotein affinity observed from Fd dependent SiR activity assay. Furthermore, Fd:SiR complex formation and interprotein affinity were thermodynamically adjusted by both enthalpy and entropy through electrostatic and non-electrostatic interactions. A residue-based NMR investigation on the addition of SiR to 15N-labeled Fd at the various NaCl concentrations also demonstrated that a combination of electrostatic and non electrostatic forces stabilized the complex with similar interfaces and modulated the binding affinity and mode. Our findings elucidate that non-electrostatic forces are also essential for the formation and modulation of the Fd:SiR complex. We suggest that a complex configuration optimized for maximum enzymatic activity near physiological salt conditions is achieved by structural rearrangement through controlled non-covalent interprotein interactions. PMID- 27551108 TI - Identification of DNAJA1 as a novel interacting partner and a substrate of human transglutaminase 2. AB - Transglutaminase 2 (TG2) is a ubiquitously expressed multifunctional member of the transglutaminase enzyme family. It has been implicated to have roles in many physiological and pathological processes such as differentiation, apoptosis, signal transduction, adhesion and migration, wound healing and inflammation. Previous studies revealed that TG2 has various intra- and extra-cellular interacting partners, which contribute to these processes. In the present study, we identified a molecular co-chaperone, DNAJA1, as a novel interacting partner of human TG2 using a GST pull-down assay and subsequent mass spectrometry analysis, and further confirmed this interaction via ELISA and surface plasmon resonance measurements. Interaction studies were also performed with domain variants of TG2 and results suggest that the catalytic core domain of TG2 is essential for the TG2-DNAJA1 interaction. Cross-linking activity was not essential for the interaction since DNAJA1 was also found to interact with the catalytically inactive form of TG2. Furthermore, we have showed that DNAJA1 interacts with the open form of TG2 and regulates its transamidation activity under both in vitro and in situ conditions. We also found that DNAJA1 is a glutamine donor substrate of TG2. Since DNAJA1 and TG2 are reported to regulate common pathological conditions such as neurodegenerative disorders and cancer, the findings in the present paper open up possibilities to explore molecular mechanisms behind TG2 regulated functions. PMID- 27551109 TI - Chemotherapy for Triple-Negative Breast Cancer: Is More Better? PMID- 27551111 TI - Baseline Metabolic Tumor Volume Predicts Outcome in High-Tumor-Burden Follicular Lymphoma: A Pooled Analysis of Three Multicenter Studies. AB - PURPOSE: Identifying patients at high risk of progression and early death among those with high-tumor-burden follicular lymphoma (FL) is unsatisfactory with current prognostic models. This study aimed to determine the prognostic impact of the total metabolic tumor volume (TMTV) measured at baseline with [18F]fluorodeoxyglucose/positron emission tomography-computed tomography ([18F]FDG/PET-CT) scans and its added value to these models. PATIENTS AND METHODS: A pooled analysis was performed by using patient data and centrally reviewed baseline PET-CT scans for 185 patients with FL who were receiving immunochemotherapy within three prospective trials. TMTV was computed by using the 41% maximum standardized uptake value thresholding method, and the optimal cutoff for survival prediction was determined. RESULTS: Median age was 55 years, 92% of patients had stage III to IV disease, 37% had a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5, and 31% had a FLIPI2 score of 3 to 5. With a median follow-up of 64 months, overall 5-year progression free survival (PFS) was 55% and overall survival (OS) was 92%. Median TMTV was 297 cm3 (quartile 1 through quartile 3, 135 to 567 cm3). The optimal cutoff identified was 510 cm3, with a markedly inferior survival in the 29% of patients with TMTV > 510 cm3. Five-year PFS was 33% versus 65% (hazard ratio [HR], 2.90; P < .001), and 5-year OS was 85% versus 95% (HR, 3.45; P = .010). On multivariable analysis, TMTV (HR, 2.3; P = .002) and FLIPI2 score (HR, 2.2; P = .002) were independent predictors of PFS. In combination, they identify three risk groups: high TMTV and intermediate-to-high FLIPI2 score with 5-year PFS of 20% (HR, 5.0; P < .001), high TMTV or intermediate-to-high FLIPI2 score with 5-year PFS of 46% (HR, 2.1; P = .007), and low TMTV and low FLIP2 with 5-year PFS of 69%. CONCLUSION: Baseline TMTV is a strong independent predictor of outcome in FL. In combination with FLIPI2 score, it identifies patients at high risk of early progression. It warrants further validation as a biomarker for development of first-line PET-adapted approaches in FL. PMID- 27551110 TI - Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History. AB - PURPOSE: To evaluate the impact of breast cancer family history and maternal BRCA1/2 mutation on the psychosocial adjustment and perceived risk in girls age 11 to 19 years old. MATERIALS AND METHODS: Girls age 11 to 19 years old with one or more relatives with breast cancer or a familial BRCA1/2 mutation (breast cancer family history [BCFH] positive, n = 208; n = 69 with BRCA1/2-positive mother), peers (BCFH negative, n = 112), and their mothers completed assessments of psychosocial adjustment, breast cancer-specific distress, and perceived risk of breast cancer. RESULTS: General psychosocial adjustment did not differ significantly between BCFH-positive and BCFH-negative girls, either by self report or mother report, except for higher self-esteem among BCFH-positive girls (P = .01). BCFH-positive girls had higher breast cancer-specific distress than BCFH-negative girls (P < .001), but girls from BRCA1/2-positive families did not differ from other BCFH-positive peers. BCFH-positive girls were more likely to report themselves at increased self-risk for breast cancer in adulthood than BCFH negative peers (74% v 33%, respectively; P <= .001). Girls from BRCA1/2-positive families were more likely than other BCFH-positive and BCFH-negative peers to report themselves at increased risk (P < .001). In all groups, perceived risk of breast cancer was associated with older age. Higher breast cancer-specific distress among adolescent girls was associated with higher self-perceived risk of breast cancer and higher maternal breast cancer-specific distress. CONCLUSION: Adolescent girls from BRCA1/2-positive and breast cancer families have higher self-esteem and do not have poorer psychosocial adjustment than peers. However, they do experience greater breast cancer-specific distress and perceived risk of breast cancer, particularly among older girls. Understanding the impact is important to optimize responses to growing up in families at familial and genetic risk for breast cancer, particularly given the debate over the genetic testing of children for cancer susceptibility in adulthood. PMID- 27551112 TI - Challenge of Prognostic Uncertainty in the Modern Era of Cancer Therapeutics. PMID- 27551113 TI - Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer. AB - Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost effective treatment strategy for patients with early-stage oral cavity cancer. PMID- 27551114 TI - Mindfulness Interventions for Cancer Survivors: Moving Beyond Wait-List Control Groups. PMID- 27551115 TI - Perils of the Pathologic Complete Response. PMID- 27551116 TI - Genome-Wide DNA Methylation Analysis Reveals Epigenetic Dysregulation of MicroRNA 34A in TP53-Associated Cancer Susceptibility. AB - PURPOSE: Although the link between mutant TP53 and human cancer is unequivocal, a significant knowledge gap exists in clinically actionable molecular targets in Li Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with germline mutations in TP53. This study surveyed the epigenome to identify functionally and clinically relevant novel genes implicated in LFS. PATIENTS AND METHODS: We performed genome-wide methylation analyses of peripheral blood leukocyte DNA in germline TP53 mutation carriers (n = 72) and individuals with TP53 wild type in whom histologically comparable malignancies developed (n = 111). Targeted bisulfite pyrosequencing was performed on a validation cohort of 30 TP53 mutation carriers and 46 patients with TP53 wild type, and candidate sites were evaluated in primary tumors from patients with LFS across multiple histologic tumor types. RESULTS: In 183 patients, distinct DNA methylation signatures were associated with deleterious TP53 mutations in peripheral blood leukocytes. TP53-associated DNA methylation marks occurred in genomic regions that harbored p53 binding sites and in genes encoding p53 pathway proteins. Moreover, loss-of-function TP53 mutations were significantly associated with differential methylation at the locus encoding microRNA miR-34A, a key component of the p53 regulatory network (adjusted P < .001), and validated in an independent patient cohort (n = 76, P < .001). Targeted bisulfite pyrosequencing demonstrated that miR-34A was inactivated by hypermethylation across many histologic types of primary tumors from patients with LFS. Moreover, miR-34A tumor hypermethylation was associated with decreased overall survival in a cohort of 29 patients with choroid plexus carcinomas, a characteristic LFS tumor (P < .05). CONCLUSION: Epigenetic dysregulation of miR-34A may comprise an important path in TP53-associated cancer predisposition and represents a therapeutically actionable target with potential clinical relevance. PMID- 27551117 TI - Definitive Management of Primary Bladder Tumors in the Context of Metastatic Disease: Who, How, When, and Why? AB - The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 70-year-old man with urothelial cancer of the bladder (UBC) metastatic to the pelvic and retroperitoneal lymph nodes was treated with gemcitabine plus cisplatin, but after two cycles neutropenic sepsis developed, which required a prolonged intensive care unit admission. Upon recovery, repeat imaging studies revealed progressive pelvic and retroperitoneal lymphadenopathy, and the patient enrolled in a clinical trial that evaluated treatment with an anti-PD-L1 antibody. The patient achieved a complete radiographic response to immune checkpoint blockade, which continued for 18 months after initiating therapy ( Fig 1 ). However, at that time, a cystoscopy of his primary tumor and a transurethral resection revealed residual muscle invasive UBC. The patient asked whether there is any role for definitive local therapy of his primary bladder tumor with radical cystectomy or radiation. PMID- 27551118 TI - A Cola to Improve My EGFR TKI Absorption in Metastatic Non-Small-Cell Lung Cancer? No, Thank You, I Prefer Lemonade or Orange Juice Instead. PMID- 27551119 TI - Clinical Utility of Biomarker Tests in Decisions on Extended Endocrine Therapy. PMID- 27551120 TI - Reply to S. Kaur et al. PMID- 27551121 TI - Reply to L.A. Renfro et al. PMID- 27551122 TI - Reply to M.J. Hall et al and K.N. Maxwell et al. PMID- 27551123 TI - Reply to D.C. Sgroi et al, T. Sanft et al, M.S. Copur et al, and M.P. Goetz et al. PMID- 27551124 TI - Small Step for Geriatric Oncology That Could Have Been a Giant Leap. PMID- 27551125 TI - Reply to R.D. Nipp et al, M.-J. Molina-Garrido et al, and A. Gajra et al. PMID- 27551126 TI - Providing Balance in ASCO Clinical Practice Guidelines: CYP2D6 Genotyping and Tamoxifen Efficacy. PMID- 27551127 TI - Population Frequency of Germline BRCA1/2 Mutations. PMID- 27551128 TI - Where Are We Headed With Research in Frail Elderly Patients With Cancer? PMID- 27551129 TI - Next-Generation Sequencing of Tumors to Better Estimate the Clinical Significance of Non- BRCA Germline Deleterious Mutations. PMID- 27551130 TI - Reply to N. Singh et al. PMID- 27551131 TI - Comprehensive Geriatric Assessment-Guided Therapy Does Improve Outcomes of Older Patients With Advanced Lung Cancer. PMID- 27551132 TI - Demystifying the Association of Chemotherapy and Cognition: How Close Are We? PMID- 27551133 TI - Surrogate End Points in Soft Tissue Sarcoma: Methodologic Challenges. PMID- 27551134 TI - Biomarkers for Early-Stage Breast Cancer: Clinical Utility for Extended Adjuvant Treatment Decisions. PMID- 27551135 TI - Reply to N. Singh et al. PMID- 27551136 TI - Multigene Panels to Evaluate Hereditary Cancer Risk: Reckless or Relevant? PMID- 27551137 TI - Reply to S.M. Sorscher and M.J. Hall et al. PMID- 27551138 TI - Recent ASCO Guideline on the Use of Biomarkers for Adjuvant Systemic Therapy in Early-Stage Invasive Breast Cancer. PMID- 27551139 TI - Reply to L.A. Renfro et al. PMID- 27551140 TI - The Impact of Leadership and Research on Decision Making: Leading Through Research. PMID- 27551141 TI - Interprofessional Collaborative Care by Dental Hygienists to Foster Medical Dental Integration. AB - The purpose of Linking Research to Clinical Practice is to present evidence based information to clinical dental hygienists so that they can make informed decisions regarding patient treatment and recommendations. Each issue will feature a different topic area of importance to clinical dental hygienists with A BOTTOM LINE to translate the research findings into clinical application. PMID- 27551142 TI - Creating Immediacy Using Verbal and Nonverbal Methods. AB - PURPOSE: The importance of immediacy and positive relationships between students and teachers is well-documented. Applying immediacy to the patient/provider model has not been sufficiently explored. The significance in creating a bond of trust between the patient/provider is vital to the diagnostic and therapeutic process. As outlined by the National Dental Hygiene Research Agenda, this literature review supports strategies for effective communication between the dental hygienist and client. It examines the relationship between oral health care providers and their patients and applies the verbal and nonverbal cues associated with immediacy to affirm their relevance and effectiveness in educating and motivating patients to achieve optimal oral and systemic health. PMID- 27551143 TI - Oral Health on Wheels: A Service Learning Project for Dental Hygiene Students. AB - PURPOSE: To provide dental hygiene students with a service learning opportunity to work with special needs and culturally diverse underserved populations through the Oral Health on Wheels (OHOW) community based mobile dental hygiene clinic. METHODS: A student feedback survey was administered between the years of 2009 and 2013 to 90 students in order to gather and identify significant satisfaction, skills acquisition and personal growth information after the student's clinical experience on the OHOW. ANOVA and Pearson correlation coefficient statistical analysis were utilized to investigate relationships between student responses to key questions in the survey. RESULTS: An analysis of 85 student responses (94.44%) demonstrated statistically significant correlations between student learning and their understanding of underserved populations, building confidence in skills, participation as a dental team member and understanding their role in total patient care. The strong correlations between these key questions related to the clinical experience and students confidence, skills integration into the dental team, and understanding of both total patient care, and the increased understanding of the oral health care needs of special populations. All questions directly link to the core mission of the OHOW program. CONCLUSION: The OHOW clinical experience allows dental hygiene students a unique opportunity to engage in their community while acquiring necessary clinical competencies required by national accreditation and providing access to oral health care services to underserved patients who would otherwise go without treatment. PMID- 27551144 TI - Factors Influencing California Dental Hygienists' Involvement in School-Based Oral Health Programs. AB - PURPOSE: To assess the influence of community oral health experiences during entry-level dental hygiene education on participation in community oral health events after graduation and the facilitators and barriers experienced by dental hygienists in participating in these programs. METHODS: A 27-item survey, consisting of items related to community oral health experiences during and after entry-level education, was distributed by the California Dental Hygienists' Association to all dental hygienists whose email addresses were in their database. Frequencies of participants' responses to each survey item were calculated. Chi-square analysis was performed to identify significant relationships among variables. RESULTS: Response rate was 8%, with 513 out of the 6,248 contacted having responded. Additionally, 95% of the respondents had participated, as entry-level students, in community oral health experiences such as school-based oral health educational programs. Respondents agreed that participation in these programs was valuable to their professional development and encouraged them to participate after graduation; both these variables were related (p<0.01) to their participation in community experiences as a licensed dental hygienist. Most (75%) respondents reported participation in community events after graduation. The most commonly reported facilitators, encouraging participation, were an interest in helping people (89%) and professional development (59%). Barriers included conflict with work (61%), family time commitment (52%), and no knowledge of existing programs (24%). CONCLUSION: Dental hygienists' involvement in school-based oral health programs is enhanced by their community experiences as a dental hygiene student. Barriers and facilitators need to be addressed to increase the number of programs and participants so that more children can benefit. PMID- 27551145 TI - Professional Caregivers' Oral Care Practices and Beliefs for Elderly Clients Aging In Place. AB - PURPOSE: As recently as the 1990s long-term care facilities (LTCFs) were the main housing option for semi- or fully-dependent elders. Today, 90% of those 65 and older want to "age in place." The growth of the elderly population that want to "age in place" will require increasing numbers of professional caregivers to assist in oral care practices. The purpose of this study was to address the gap in the knowledge about the oral care practices and beliefs of professional caregivers who work for non-medical in-home care companies charged in the care of "aging in place" elders. METHODS: The Nursing Dental Coping Belief Scale was used in a descriptive cross-sectional study. Professional caregivers (n=67) employed by 3 non-medical in-home care companies in South Texas completed the survey. The survey gathered demographic information, oral care practice questions and oral health belief questions. Statistics used for data analysis included chi-square contingency table analysis. The level of significance was set at p<0.05 for all analyses. RESULTS: Non-medical in-home care companies are not mandated by law to provide training, yet professional caregivers wanted more training in brushing and flossing (85%). A majority (60%) reported being trained. Most (85%) looked inside their client's mouth yet nearly 18% did not floss their client's teeth and only 31% knew if their clients wore dentures. CONCLUSION: While this was a small study, it provides preliminary information that professional caregivers, who serve clients aging in place, want more oral care training. Professional caregivers would be better served if there were more thorough and frequent training provided with managerial oversight. PMID- 27551146 TI - Attitudes of Dental Hygienists towards Independent Practice and Professional Autonomy. AB - PURPOSE: The purpose of this cross-sectional, quantitative research was to examine if registered dental hygienists feel competent to work independently based on regulations of dental supervision. METHODS: A stratified sample of 360 dental hygienists from 8 states completed the Dempster Practice Behaviors Scale survey. ANOVA and MANOVA analyses revealed how state dentist supervision level, age, degree of education, employment status, gender and years of clinical experience affect the perceived autonomy of professional dental hygienists. RESULTS: The response rate included 360 dental hygienists from 8 states. According to the findings age, education level and gender affected the hygienist's level of autonomy. In all 8 states, the registered dental hygienists have a high level of autonomy and feel competent to work independently. CONCLUSION: The DPBS scores of the sample registered dental hygienists suggest that they feel prepared and competent to perform preventive dental hygiene services without dentist supervision. The attitudes of the dental hygienist sample from each of the 4 state dentist supervision levels supports a move toward achieving professional jurisdiction of preventive dental care within the U.S. PMID- 27551147 TI - Evaluating Student Self-Assessment through Video-Recorded Patient Simulations. AB - PURPOSE: The purpose of this pilot study was to determine if the use of a video recorded clinical session affects the accuracy of dental hygiene student self assessment and dental hygiene instructor feedback. METHODS: A repeated measures experiment was conducted. The use of the ODU 11/12 explorer was taught to students and participating faculty through video and demonstration. Students then demonstrated activation of the explorer on a student partner using the same technique. While faculty completed the student assessment in real time, the sessions were video recorded. After completing the activation of the explorer, students and faculty completed an assessment of the student's performance using a rubric. A week later, both students and faculty viewed the video of the clinical skill performance and reassessed the student's performance using the same rubric. The student videos were randomly assigned a number, so faculty reassessed the performance without access to the student's identity or the score that was initially given. RESULTS: Twenty-eight students and 4 pre-clinical faculty completed the study. Students' average score was 4.68+/-1.16 on the first assessment and slightly higher 4.89+/-1.45 when reviewed by video. Faculty average scores were 5.07+/-2.13 at the first assessment and 4.79+/-2.54 on the second assessment with the video. No significant differences were found between the differences in overall scores, there was a significant difference in the scores of the grading criteria compared to the expert assessment scores (p=0.0001). CONCLUSION: This pilot study shows that calibration and assessment without bias in education is a challenge. Analyzing and incorporating new techniques can result in more exact assessment of student performance and self assessment. PMID- 27551148 TI - Combining Tpi and CO1 Genetic Markers to Discriminate Invasive Helicoverpa armigera From Local Helicoverpa zea (Lepidoptera: Noctuidae) Populations in the Southeastern United States. AB - The recent establishment of the Old World pest Helicoverpa armigera (Hubner) into South America has had significant economic consequences and places the rest of the hemisphere at risk, emphasizing the need for improved methods of monitoring. A major complication is that a sibling species endemic to the New World, Helicoverpa zea (Boddie), is morphologically very similar, with the two species capable of producing fertile hybrids in the laboratory. The consequences of such hybridization in the field are uncertain, but could result in significant and unpredictable changes in the timing, range, and pesticide susceptibilities of Helicoverpa infestations. The objective here is to provide new genetic resources applicable to Helicoverpa populations in northern Florida and neighboring states (a region at risk for H. armigera) that can distinguish the two species and possible hybrids. The genetic variability in segments of the mitochondrial cytochrome oxidase 1 (CO1) and the Z-linked triosephosphate isomerase (Tpi) genes were determined for H. zea from the southeastern United States. These were compared to DNA sequences from H. armigera specimens from Morocco, Australia, and Europe. Phylogenetic network analysis showed a clear demarcation between the two species for all gene segments. These results extend earlier studies establishing CO1 as marker for discriminating the Helicoverpa species complex and introduce a new sex-linked genomic marker. The CO1 and Tpi markers in combination provide a more accurate and sensitive method than existing techniques for identifying hybridization between H. zea and H. armigera and could potentially be used to extrapolate the likely source of invasive H. armigera populations. PMID- 27551149 TI - Does Drought Increase the Risk of Insects Developing Behavioral Resistance to Systemic Insecticides? AB - Increases in severity and frequency of drought periods, average global temperatures, and more erratic fluctuations in rainfall patterns due to climate change are predicted to have a dramatic impact on agricultural production systems. Insect pest populations in agricultural and horticultural systems are also expected to be impacted, both in terms of their spatial and temporal distributions and in their status as pest species. In this opinion-based article, we discuss how indirect effects of drought may adversely affect the performance of systemic insecticides and also lead to increased risk of insect pests developing behavioral insecticide resistance. We hypothesize that more pronounced drought will decrease uptake and increase the magnitude of nonuniform translocation of systemic insecticides within treated crop plants, and that may have two concurrent consequences: 1) reduced pesticide performance, and 2) increased likelihood of insect pests evolving behavioral insecticide resistance. Under this scenario, pests that can sense and avoid acquisition of lethal dosages of systemic insecticides within crop plants will have a selective advantage. This may lead to selection for insect behavioral avoidance, so that insects predominantly feed and oviposit on portions of crop plants with low concentration of systemic insecticide. Limited research has been published on the effect of environmental variables, including drought, on pesticide performance, but we present and discuss studies that support the hypothesis described above. In addition, we wish to highlight the importance of studying the many ways environmental factors can affect, directly and indirectly, both the performance of insecticides and the risk of target insect pests developing resistance. PMID- 27551150 TI - Characterization and Growing Development of Spodoptera exigua (Lepidoptera: Noctuidae) Larvae Infected by Heliothis virescens ascovirus 3h (HvAV-3h). AB - Spodoptera exigua (Hubner) is a very serious worldwide pest capable of causing severe economic losses in numerous agricultural crops. The need for an effective, highly virulent, pathogenic microorganism for use as a biological control agent against S. exigua larvae is particularly important. Heliothis virescens ascovirus 3 h (HvAV-3h)-containing hemolymph with a titer of 9.58 * 10(12) genome copies per ml was used to inoculate S. exigua larvae per os with a 1.06 * 10(10) dosage per larva for the first- to second instar and 9.58 * 10(9) genome copies per larva for the third- to fifth instars. Intrahemocoelic injections were also used with a dosage of 1.53 * 10(9) genome copies per larva for third- to fifth instar. The postinjection mortality, body weight, and food intake of the S. exigua larvae were observed and recorded. The corrected mortality rates for the first- through fifth instar inoculated per os were 21.88 +/- 0.98, 22.22 +/- 4.00, 8.89 +/- 4.01, 6.66 +/- 3.33, and 8.89 +/- 2.94%, respectively. The early instars were significantly easier to infect with virus compared to the later instar. The corrected mortality of the third, fourth, and fifth instars inoculated by injection was 96.58 +/- 3.42, 98.83 +/- 1.17, and 97.78 +/- 2.22%, respectively. Compared to the healthy larval population, survival time of the diseased larval population was considerably extended. In addition, food intake was greatly reduced, and the body weight remained fairly constant in the third- and fourth instar. The body weight declined in the fifth instar corresponding to a reduction in food intake. PMID- 27551151 TI - Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion. AB - Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. PMID- 27551152 TI - MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes. AB - Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80(+) macrophages and MHC II(+) CD11c(+) macrophages. F4/80(+) macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II(+) macrophages remain unknown. Here, we show that the MHC II(+) macrophages arise postnatally from CCR2 dependent precursors that resemble monocytes. Monocytes continuously replenish this subset through adulthood. Gene expression analysis identified distinct surface markers like CD226 and revealed that the transcription factor IRF4 was selectively expressed in these macrophages relative to other organs. Monocytes first entered peritoneal or pleural cavities to become MHC II(+) cells that up regulated CD226 and CD11c later as they continued to mature. In the absence of IRF4 or after administration of oral antibiotics, MHC II(+)CD226(-)CD11c(-) monocyte-derived cells accumulated in peritoneal and pleural cavities, but CD11c(+) CD226(+) macrophages were lost. Thus, MHC II(+) resident peritoneal and pleural macrophages are continuously replenished by blood monocytes recruited to the peritoneal and pleural cavities constitutively, starting after birth, where they require IRF4 and signals likely derived from the microbiome to fully differentiate. PMID- 27551153 TI - G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling. AB - Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID- 27551154 TI - Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression. AB - HIV-1 adapts to a new host through mutations that facilitate immune escape. Here, we evaluate the impact on viral control and disease progression of transmitted polymorphisms that were either preadapted to or nonassociated with the new host's HLA. In a cohort of 169 Zambian heterosexual transmission pairs, we found that almost one-third of possible HLA-linked target sites in the transmitted virus Gag protein are already adapted, and that this transmitted preadaptation significantly reduced early immune recognition of epitopes. Transmitted preadapted and nonassociated polymorphisms showed opposing effects on set-point VL and the balance between the two was significantly associated with higher set point VLs in a multivariable model including other risk factors. Transmitted preadaptation was also significantly associated with faster CD4 decline (<350 cells/ul) and this association was stronger after accounting for nonassociated polymorphisms, which were linked with slower CD4 decline. Overall, the relative ratio of the two classes of polymorphisms was found to be the major determinant of CD4 decline in a multivariable model including other risk factors. This study reveals that, even before an immune response is mounted in the new host, the balance of these opposing factors can significantly influence the outcome of HIV 1 infection. PMID- 27551155 TI - IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. AB - Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4(+) T cells to induce IL-22 production. However, the mechanisms that drive IL 23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4(+) T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD. PMID- 27551158 TI - Interfacial magnetic anisotropy from a 3-dimensional Rashba substrate. AB - We study the magnetic anisotropy which arises at the interface between a thin film ferromagnet and a 3-d Rashba material. We use a tight-binding model to describe the bilayer, and the 3-d Rashba material characterized by the spin-orbit strength alpha and the direction of broken bulk inversion symmetry n. We find an in-plane uniaxial anisotropy in the z * n direction, where z is the interface normal. For realistic values of alpha, the uniaxial anisotropy is of a similar order of magnitude as the bulk magnetocrystalline anisotropy. Evaluating the uniaxial anisotropy for a simplified model in 1-d shows that for small band filling, the in-plane easy axis anisotropy scales as alpha4 and results from a twisted exchange interaction between the spins in the 3-d Rashba material and the ferromagnet. For a ferroelectric 3-d Rashba material, n can be controlled with an electric field, and we propose that the interfacial magnetic anisotropy could provide a mechanism for electrical control of the magnetic orientation. PMID- 27551156 TI - Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. AB - Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic, and degenerative diseases in humans. In this study, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida Genetic deletion or pharmacological inhibition of cathepsin B down-regulated mechanistic target of rapamycin activity and prevented cleavage of the lysosomal calcium channel TRPML1. These events drove transcription of lysosomal and autophagy genes via transcription factor EB, which increased lysosomal biogenesis and activation of autophagy initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome populations and basic recycling functions in the cell. PMID- 27551157 TI - NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20. AB - Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells. PMID- 27551159 TI - The Contribution of Segmental and Suprasegmental Phonology to Reading Comprehension. AB - The aim of the present study was to examine the relation between decoding and segmental and suprasegmental phonology, and their contribution to reading comprehension, in the upper primary grades. Following a longitudinal design, the performance of 99 Dutch primary school children on phonological awareness (segmental phonology) and text reading prosody (suprasegmental phonology) in fourth-grade and fifth-grade, and reading comprehension in sixth-grade were examined. In addition, decoding efficiency as a general assessment of reading was examined. Structural path modeling firstly showed that the relation between decoding efficiency and both measures of phonology from fourth- to fifth grade was unidirectional. Secondly, the relation between decoding in fourth- and fifth grade and reading comprehension in sixth-grade became indirect when segmental and suprasegmental phonology were added to the model. Both factors independently exerted influence on later reading comprehension. This leads to the conclusion that not only segmental, but also suprasegmental phonology, contributes substantially to children's reading development. PMID- 27551160 TI - Formation and Trapping of Azafulvene Intermediates Derived from Manganese Mediated Oxidative Malonate Coupling. AB - The one-pot, three-component, coupling reaction of indoles/pyrroles, dimethyl malonate, and acetic acid was performed using Mn(III) acetate as an oxidant. In the presence of Mn(OAc)3, indole-2, and indole-3-carbonyl compounds were alkylated at the 3- and 2- positions, respectively, with subsequent oxidation and nucleophilic capture occurring at the newly formed benzylic carbon. In contrast, oxidation of 2- and 3-indole carboxylic acids afforded the corresponding 2 oxindol-3-ylidenes and 3-oxindol-2-ylidenes. The reaction conditions, scope, and mechanism are discussed herein. PMID- 27551162 TI - Stress-related changes in personality: A longitudinal study of perceived stress and trait pessimism. AB - Although research has shown that certain aspects of personality can change over time, the determinants of such change remain unclear. Stress alters neural dynamics and precipitates disorders that shape personality traits involving negative affectivity. In this study, therefore, we assessed the perceived stress and pessimism levels of 332 young, middle-aged, and older adults for five weeks to examine how levels of stress and pessimism change and interrelate over time. The best fitting longitudinal model was a bivariate latent growth curve model, which indicated that stress and pessimism both changed and exhibited significant variability in change over time. Moreover, changes in stress were associated with changes in pessimism. Pessimism thus changes over time, with alterations in stress potentially structuring these changes. PMID- 27551164 TI - A New Face Uplift. PMID- 27551163 TI - pH Responsive and Oxidation Resistant Wet Adhesive based on Reversible Catechol Boronate Complexation. AB - A smart adhesive capable of binding to a wetted surface was prepared by copolymerizing dopamine methacrylamide (DMA) and 3-acrylamido phenylboronic acid (AAPBA). pH was used to control the oxidation state and the adhesive property of the catechol side chain of DMA and to trigger the catechol-boronate complexation. FTIR spectroscopy confirmed the formation of the complex at pH 9, which was not present at pH 3. The formation of the catechol-boronate complex increased the cross-linking density of the adhesive network. Most notably, the loss modulus values of the adhesive were more than an order of magnitude higher for adhesive incubated at pH 9 when compared to those measured at pH 3. This drastic increase in the viscous dissipation property is attributed to the introduction of reversible complexation into the adhesive network. Based on the Johnson Kendall Roberts (JKR) contact mechanics test, adhesive containing both DMA and AAPBA demonstrated strong interfacial binding properties (work of adhesion (Wadh) = 2000 mJ/m2) to borosilicate glass wetted with an acidic solution (pH 3). When the pH was increased to 9, Wadh values (180 mJ/m2) decreased by more than an order of magnitude. During successive contact cycles, the adhesive demonstrated the capability to transition reversibly between its adhesive and nonadhesive states with changing pH. Adhesive containing only DMA responded slowly to repeated changes in pH and became progressively oxidized without the protection of boronic acid. Although adhesive containing only AAPBA also demonstrated strong wet adhesion (Wadh ~ 500 mJ/m2), its adhesive properties were not pH responsive. Both DMA and AAPBA are required to fabricate a smart adhesive with tunable and reversible adhesive properties. PMID- 27551165 TI - Melone's Concept Revisited: 3D Quantification of Fragment Displacement. AB - We applied quantitative 3D computed tomography to 50 complete articular AO type C fractures of the distal radius and tested the null hypothesis that fracture fragments can be divided according to Melone's concept (radial styloid and volar and dorsal lunate facet fragments) and that each fragment has similar (1) displacement and (2) articular surface area. Thirty-eight fractures fit the Melone distribution of fragments. Radial styloid fragments were most displaced, and volar lunate fragments were least displaced. Volar lunate fragments had the largest articular surface area. While these findings confirm Melone's concepts, the finding that volar lunate fragments are relatively large and dorsal lunate fragments relatively small suggests that alignment of the volar lunate fragment with the radial styloid may be the key element of treatment and the dorsal lunate fragment may not routinely benefit from specific reduction and fixation. PMID- 27551166 TI - Cocaine-Induced Abnormal Cerebral Hemodynamic Responses to Forepaw Stimulation Assessed by Integrated Multi-wavelength Spectroimaging and Laser Speckle Contrast Imaging. AB - Simultaneous imaging of cerebral hemodynamic changes in response to functional activation during drug intoxication provides a valuable strategy to assess cocaine induced neurovascular dysfunction. However, this requires tools with sufficient spatiotemporal resolution and adequate signal to noise ratio (SNR). Though several technologies have been developed to address this demand during functional brain activation, their spatiotemporal resolution has been compromised to preserve SNR. In this study, we combine spatiotemporal-domain laser speckle contrast analysis and image correlation techniques to integrate multi-wavelength spectroimaging and laser speckle contrast imaging (MW-LSCI). Experimental results show that optimized spatiotemporal resolution with enhanced SNR were achieved that enabled simultaneous measurement of multiple hemodynamic responses (i.e., DeltaHbO2, DeltaHbR, DeltaHbT and DeltaCBF) during cocaine administration. Specifically, cocaine-induced functional cerebral hemodynamic changes were accessed by measuring the activation responses to forepaw electrical stimulation at different times after cocaine administration. With improved spatiotemporal resolution and SNR, the system was able to differentiate the heterogeneity of cocaine's effects on the cerebral vasculature and on tissue metabolism, demonstrating the unique capability of MW-LSCI for various brain functional and pharmacological studies. PMID- 27551167 TI - The Codes of Publication Policy of the Eurasian Journal of Medicine: Parameters for a Stable and Sustainable Journal. PMID- 27551168 TI - Once the Light Touch to the Brain: Cytotoxic Effects of Low-Dose Gamma-Ray, Laser Light, and Visible Light on Rat Neuronal Cell Culture. AB - OBJECTIVE: We aimed to evaluate the effects of gamma-ray, laser light, and visible light, which neurons are commonly exposed to during treatment of various cranial diseases, on the viability of neurons. MATERIALS AND METHODS: Neuronal cell culture was prepared from the frontal cortex of 9 newborn rats. Cultured cells were irradiated with gamma-ray for 1-10 min by (152)Eu, (241)Am, and (132)Ba isotopes, visible light for 1-160 min, and laser light for 0.2-2 seconds. The MTT tetrazolium reduction assay was used to assess the number of viable cells in the neuronal cell cultures. Wavelength dispersive X-ray fluorescence spectrometer was used to determine Na, K, and Ca levels in cellular fluid obtained from neuronal cell culture plaques. RESULTS: Under low-dose radiation with (152)Eu, (241)Am, and (132)Ba isotopes, cell viability insignificantly decreased with time (p>0.05). On the other hand, exposure to visible light produced statistically significant decrease in cell viability at both short- (1 10 min) and long-term (20-160 min). Cell viability did not change with 2 seconds of laser exposure. Na, K, and Ca levels significantly decreased with gamma-ray and visible light. The level of oxidative stress markers significantly changed with gamma-ray. CONCLUSION: In conclusion, while low dose gamma-ray has slight to moderate apoptotic effect in neuronal cell cultures by oxidative stress, long term visible light induces remarkable apoptosis and cell death. Laser light has no significant effect on neurons. Further genetic studies are needed to clarify the chronic effect of visible light on neuronal development and functions. PMID- 27551169 TI - Modified Primary Closure Method for the Treatment of Pilonidal Sinus. AB - OBJECTIVE: Pilonidal sinus (PS) is considered to be the acquired disease of especially in the sacrococcygeal region. Various primary or secondary or flap methods, accompanied by one of local curettage, phenol application, electro cauterization and total sinus excision methods, are used for the treatment of pilonidal sinus. However, currently there is not a single widely accepted treatment method. MATERIALS AND METHODS: Ninety-eight patients who had operation for PS in Ataturk University, Department of General Surgery between January 2012 and August 2014 were included in this study. The patients were categorized into two groups: first, the patients undergone total sinus excision with primary closure (Group 1), and second, patients undergone total sinus excision with modified primary closure (MPC) (Group 2). Among all 98 patients participated in this study, age, sex, type of operation, duration of operation, amount of excised skin, duration of postoperative stay at hospital and complications were evaluated. RESULTS: Forty-four patients (44.9%) underwent primary closure method, while 54 patients (55.1%) underwent MPC method. Mean duration of operation was 39.1 (30-60) minutes, mean diameter of excised material was 9.3 (8-11) cm(2) and mean duration of stay at hospital was 1.4 (1-3) days for the patients in the first group. Meanwhile, duration of operation was 52.2 (35-70) minutes, mean diameter of excised material was 2.6 (2-4) cm(2) and mean duration of stay at hospital was 1.6 (1-3) days for the patients in the second group. There was statistically significant difference between the two groups by means of duration of operation, dehiscence of surgical wound, recurrence and development of general complications (p<0.001, p<0.05, p<0.05 and p<0.005, respectively). According to the multivariate analysis, during surgical treatment of pilonidal sinus, primary closure method increases the rate of complication 6.65 times and MPC method increases the duration of operation 1.2 times. CONCLUSION: We hereby suggest that MPC method could be a good alternative for surgical treatment of PS, because it causes fewer complications and recurrence. PMID- 27551170 TI - The Distribution of Apolipoprotein E Gene Polymorphism and Apolipoprotein E Levels among Coronary Artery Patients Compared to Controls. AB - OBJECTIVE: Coronary artery disease (CAD) is a multifactorial disease that is caused by various genetics and environmental factors. Genetically, predisposition is an important component for CAD. The candidate apolipoprotein E (apoE) gene is the most studied one. ApoE is composed of e2, e3, e4 alleles and E2/2, E2/3, E2/4, E3/3, E3/4, E4/4 genotypes. In this study, the relationship between CAD and apoE polymorphism and apoE level has been studied in Tokat region. MATERIALS AND METHODS: The study population is composed of 100 CAD patients diagnosed by coronary angiography and 100 control patients of whom fifty have normal coronary angiography and fifty did not have any CAD symptoms. The serum lipid and apoE levels and apoE genotypes of all participants have been measured, and the relationship between these parameters has been evaluated. RESULTS: Apolipoprotein E, total cholesterol, HDL cholesterol and LDL cholesterol levels were statistically low at CAD patients than control patients (p=0.0004, p=0.0005, p=0.0107, p=0.0052 respectively). There was not any significant difference between triglyceride levels (p=0.0848). Waist circumferences were significantly high at CAD patients (p=0.0012). Allele frequencies were as e2 (7.25%), e3 (83.5%), e4 (9.25%) and genotype distributions were as E2/2 (0.5%), E2/3 (13%), E2/4 (0.5%), E3/3 (68.5%), E3/4 (16.5%), E4/4 (1%). The distribution of alleles and genotypes were not significantly different (p>0.05). ApoE levels were higher at e2 allele carriers than e3 and e4 allele carriers (p<0.05). However, there was no significant difference between e3 and e4 allele carriers. CONCLUSION: In conclusion, the distribution of apoE genotype and allele at our region is similar to the general of Turkey. The low apoE levels in CAD patients may show the influence of apoE on CAD by local and systemic mechanisms. PMID- 27551171 TI - Effects of Native Type II Collagen Treatment on Knee Osteoarthritis: A Randomized Controlled Trial. AB - OBJECTIVE: The aim of this randomized controlled study was to evaluate the efficacy of oral native type II collagen treatment on the symptoms and biological markers of cartilage degradation, when given concomitantly with acetaminophen in patients with knee osteoarthritis. MATERIALS AND METHODS: Thirty-nine patients diagnosed with knee osteoarthritis were included and randomly distributed into two groups: one treated with 1500 mg/day of acetaminophen (group AC; n=19) and the other treated with 1500 mg/day of acetaminophen plus 10 mg/day of native type II collagen (group AC+CII; n=20) for 3 months. Visual Analogue Scale (VAS) at rest and during walking, Western Ontario McMaster (WOMAC) pain, WOMAC function, and Short Form-36 (SF-36) scores, were recorded. Coll2-1, Coll2-1NO2 and Fibulin 3 levels were quantified in urine as biomarkers of disease progression. ClinicalTrials.gov: NCT02237989. RESULTS: After 3 months of treatment, significant improvements compared to baseline were reported in joint pain (VAS walking), function (WOMAC) and quality of life (SF-36) in the AC+CII group, while only improvements in some subscales of the SF-36 survey and VAS walking were detected in the AC group. Comparisons between the groups revealed a significant difference in VAS walking score in favour of the AC+CII group as compared to AC group. Biochemical markers of cartilage degradation in urine did not significantly improve in any of the groups. CONCLUSION: All in all, these results suggest that native type II collagen treatment combined with acetaminophen is superior to only acetaminophen for symptomatic treatment of patients with knee osteoarthritis. PMID- 27551172 TI - Psychological Evaluation of Patients Seeking Rhinoplasty. AB - OBJECTIVE: The aim of this study was to evaluate different determinants of the patient's psychosocial functioning that might possibly affect the outcome of rhinoplastic surgery. MATERIALS AND METHODS: Forty-one patients undergoing rhinoplasty, consecutively admitted to and operated upon at the Department of Otolaryngology, Erzurum Regional Training and Research Hospital, Turkey, were studied with regard to their psychological characteristics. RESULTS: In the patient group, Liebowitz anxiety, Liebowitz/avoidance, and Liebowitz/total scores were significantly higher than the control group (p<0.001). No significant differences were found between the patient and control groups according to Rosenberg self-esteem scale and The Hospital Anxiety and Depression Scale. In the Quality of Life SF-36 results, significant differences were found between the patient and control groups apart from SF-36 scores of pain (p<0.05), vitality (p<0.05), social functioning (p<0.05) and emotional role difficulties (p<0.05). CONCLUSION: Patient selection must be done very carefully to obviate not only physical, but also psychological postoperative complications. The SF-36 questionnaire may be of value in screening-patients for psychological problems prior to rhinoplasty. PMID- 27551173 TI - Dermatological Findings in Turkish Paediatric Haematology-Oncology Patients. AB - OBJECTIVE: Diagnoses of skin, mucosae, hair and nail manifestations in malignant diseases are often challenging because of life-threatening drug reactions, opportunistic infections or skin involvement of primary processes. Description of morphology, configuration and distribution of lesions is important in order to differentiate the self-healing eruptions from serious side effects of chemotherapy. There are case reports from Turkey including dermatological manifestations of malignancies and case series in adult patients but there are no published large group studies assessing all manifestations in children. The aim of this study was to evaluate the morphological features of dermatological findings in children with haemato-oncological diseases. MATERIALS AND METHODS: The study was performed at the Erciyes University, Faculty of Medicine Pediatric Hematology-Oncology Clinic, Turkey. Three dermatologists daily consulted all patients admitted to the clinic during a one-year period. RESULTS: The study group comprised of 157 children (79 female/78 male) aged 1-16 years (mean 7.19+/ 4.63). Detailed dermatological examinations were performed, including oral genital mucosae, hair and nails. Thorough skin examination revealed that 70% of the patients exhibited at least one dermatological finding. Generalized xerosis and hyperpigmentation were the most common findings among patients undergoing chemotherapy (24.19%). Multiple nevi on at least 10 covered areas were very frequent among patients undergoing long-term chemotherapy (18.47%). Three were identified as dysplastic nevus, but malignant transformation was not observed during the one-year study period. CONCLUSION: Regular dermatological consultation may help resolve the diagnostic and therapeutic problems in paediatric haemato oncology clinics. PMID- 27551174 TI - Inequity in Health Care Financing in Iran: Progressive or Regressive Mechanism? AB - OBJECTIVE: Having progressive health finance mechanism is very important to decrease inequity in health systems. Revenue collection is one of the aspects of health care financing. In this study, taxation system and health insurance contribution of Iranians were assessed. MATERIALS AND METHODS: Data of 2012 household expenditures survey were used in this study, and payments of the families for health insurances and tax payments were extracted from the study. Kakwani index was calculated for assessing the progressivity of these payments. At the end, a model was designed to find the effective factors. RESULTS: We found that taxation mechanism was progressive, but insurance contribution mechanism was very regressive. The portion of people living in urban regions was higher in the payments of insurance and tax. Less educated families had lower contribution in health insurance and families with more aging persons paid more for health insurance. CONCLUSION: Policy makers must pay more attention to the health insurance contribution and change the laws in favour of the poor. PMID- 27551175 TI - Foreign Bodies in Trachea: A 25-years of Experience. AB - OBJECTIVE: Tracheobronchial foreign body aspirations may cause cardiopulmonary arrest and sudden death. The incidence in children is higher than in adults. Rapid diagnosis and treatment is live saving. In this paper, we aimed to present our experience in tracheal foreign body aspirations and rigid bronchoscopy for 25 years. MATERIALS AND METHODS: From January 1990 to January 2015, 805 patients with suspected tracheobronchial foreign body aspiration were admitted to our department. Hundred and twelve patients with tracheal foreign body were included in this study. We evaluated patients' records, retrospectively. Age, gender, clinical symptoms, physical examination findings, radiological evidences, type of foreign body and intervention types were noted. RESULTS: Sixty-five of the patients were female (58%) and 47 patients were male (42%), and mean age was 8.1 years (8 month-58 years). Coughing was the main symptom (n=112, 100%). Other symptoms and findings included dyspnoea and bilateral decreased lung sounds (n=73, 65.1%), bilateral rhonchi (n=68, 60.7%) and cyanosis (n=41, 36.6%). Rigid bronchoscopy was performed in all patients. The most common foreign body was nuts (n=75, 67%). The main radiologic finding was radiopaque image of the related foreign body in 27 patients (n=27, 24.1%). Cardio-pulmonary arrest occurred in 11 patients and two of them died. CONCLUSION: Tracheobronchial aspirations of foreign bodies are life-threatening events. If not diagnosed and treated rapidly, distressful results can be seen. Warning people by skilled persons on this topic will reduce the incidence of foreign body aspirations. PMID- 27551176 TI - Comparison of Various Methods in the Diagnosis of Entamoeba histolytica in Stool and Serum Specimens. AB - OBJECTIVE: Entamoeba histolytica is indistinguishable from Entamoeba dispar in direct microscopic examination. A definitive diagnosis of E. histolytica is important in terms of the treatment of the patient and to avoid unnecessary costs. This study's aim is to determine the prevalence of E. histolytica and to make a comparison of the different diagnostic tests in the patients specimens defined as E. histolytica/E. dispar infection. MATERIALS AND METHODS: Faecal and serum specimens of 90 patients defined as E. histolytica/E. dispar with microscopy (wet mount examination with 0.85% saline and Lugol's iodine) were examined. Stool samples were examined by trichrome staining for trophozoites and cysts and by immunoassay methods for specific adhesin antigens (Wampole ((r)) E. histolytica II antigen testing) and for specific serine-rich 30 kD membrane protein (Serazym((r)) E. histolytica antigen testing). Anti-E. histolytica antibodies were investigated using a latex slide test and indirect hemagglutination methods in serum specimens. RESULTS: Presence of E. histolytica was not confirmed in 31.1% cases with trichrome staining, 62.2% of the Wampole antigen test, 64.4%, of the Serazym antigen test, 73.3% of the indirect hemagglutination test and 75.6%. of the latex agglutination. Considering the common results from Wampole and Serazym antigen testing as a reference standard, the specificity/sensitivity is 100/53.85% for trichrome staining, 75.00/98.11% for the latex agglutination test and 78.57/96.77% for the indirect hemagglutination test. CONCLUSION: It has been shown that investigation of E. histolytica in stools by direct wet-smear microscopy alone can cause significant false positive results. To obtain a reliable diagnosis for E. histolytica and to avoid unnecessary treatment for this parasite, at least one more specific assay, particularly an antigen testing and microscopy, is required. PMID- 27551177 TI - Obstetric Outcomes in Non-Gynecologic Cancer Patients in Remission. AB - OBJECTIVE: The aim of the present study was to evaluate the obstetric and perinatal outcomes in treated women who were diagnosed with non-gynecologic cancer and to compare these findings with pregnant women with no history of cancer. MATERIALS AND METHODS: This retrospective study was conducted on 21 pregnant women with non-gynecologic cancer who were in remission (study group) and 63 pregnant women with no history of cancer (control group). The women were admitted to the high-risk pregnancy clinic of Zekai Tahir Burak Women's Health Training and Research Hospital with a diagnosis of pregnancy and cancer between January 2010 and January 2015. Obstetric outcomes and demographic characteristics of the patients were recorded. Age, gravida, parity, abortus, body mass index (BMI), gestational week, smoking, mode of delivery, gestational weight, and perinatal outcomes were examined for each woman. RESULTS: The most common cancer types were thyroid (28.5%) and breast cancers (23.8%), which constituted just over half of the non-gynecologic cancer cases during pregnancy. The time elapsed after the diagnosis was 3.8+/-2.2 (1-9) years. No statistically significant differences were found between the two groups with regard to age, obstetric history, BMI, gestational week, smoking, and obstetric and perinatal outcomes (p>0.05). CONCLUSION: Negative perinatal outcomes in non-gynecologic cancer patients in remission were found to be within acceptable levels. PMID- 27551179 TI - Cutaneous Anthrax on Eyelid in a Pregnant Woman. AB - A 32-year-old patient who was 17 weeks of pregnant referred to our hospital due to a lesion on the eyelid and swelling on her face. Patient's history revealed that she helped her husband for slaughtering of a sick animal and contacted with the meat. A scabby lesion was detected on the inferior eyelid with hyperaemia around, central necrotic appearance and swelling. The diagnosis of anthrax was performed based on her epidemiological data, physical examination findings, and Bacillus anthracis were seen on direct preparation. This case was considered worthy to present since she was pregnant, the disease was located on the inferior eyelid, which is a rare place for location, and caused no complication or sequel either in mother or in baby. PMID- 27551178 TI - A Review of Melatonin, Its Receptors and Drugs. AB - After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORalpha: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. PMID- 27551180 TI - IgE-Mediated Reaction to Metamizole: Evaluation of a Patient with Severe Anaphylaxis. AB - Metamizole, a non-steroidal anti-inflammatory drug with weak anti-inflammatory and spasmolytic effects, is used as an analgesic and antipyretic agent. Many adverse reactions to metamizole, such as early or late-onset systemic reactions and bone marrow suppression, have been identified. In this report, we present a case of systemic reaction after the application of parenteral metamizole (Novalgin((r)) ampoule; Sanofi Aventis, Istanbul, Turkey) and discuss the mechanism underlying the reaction. PMID- 27551181 TI - A Case of Alveolar Echinococcosis Presenting as Cerebral and Spinal Intradural Metastases. AB - Alveolar echinococcosis is a chronic and serious, even lethal, parasitic infection caused by the helminth Echinococcus multilocularis. The involvement of Central Nervous System is reported to be 1-3% in literature. Brain involvement is considered a sign of the terminal phase of alveolar echinococcosis. We here in reported a 67-year-old female who had liver alveolar hydatid disease with brain and spinal intradural metastases. PMID- 27551183 TI - Erratum. AB - [This corrects the article on p. 130 in vol. 47, PMID: 26180498.]. PMID- 27551182 TI - Laparascopic Splenectomy Due to Splenic Injury after Colonoscopy. AB - Colonoscopy, which is routinely performed in diagnosis and treatment of colorectal disorders, is a reliable procedure. Its most frequent complications are bleeding and perforation. Splenic rupture is a very rarely met complication of colonoscopy, and delay in its diagnosis leads to increased morbidity and mortality. We presented a 69 years old female patient, who was diagnosed by computerized abdominal tomography, performed for her abdominal pain, which started following the colonoscopy. After 15 days of medical treatment and follow up, laparoscopic splenectomy was performed one month after her colonoscopy. The patient was discharged on her 4(th) postoperative day, with uneventful recovery. In patients who have complaint of abdominal pain following colonoscopy, an intraabdominal pathological condition should be considered and computerized abdominal tomography should be performed. If there is no detected intraperitoneal bleeding, in other words, if there is a sub-capsular hematoma of the spleen, medical management by monitoring the vital signs may be preferred. Then, splenectomy should be performed at an appropriate time. PMID- 27551184 TI - Three new species of western California springsnails previously confused with Pyrgulopsis stearnsiana (Caenogastropoda, Hydrobiidae). AB - We describe three new, allopatric species of springsnails (genus Pyrgulopsis) from western California (Pyrgulopsis lindae, Pyrgulopsis ojaiensis, Pyrgulopsis torrida) that were previously identified as Pyrgulopsis stearnsiana. The new species are differentiated from Pyrgulopsis stearnsiana and each other both by mtCOI sequences (3.9-9.9%) and details of penial morphology. We also provide a phylogeny with increased sampling which confirms a previous finding that Pyrgulopsis stearnsiana sensu stricto is paraphyletic relative to two other California species (Pyrgulopsis diablensis, Pyrgulopsis giulianii). Our molecular and morphological evidence suggests that Pyrgulopsis stearnsiana paraphyly is an artifact of conservative taxonomy, however additional studies utilizing rapidly evolving genetic markers will be needed to confidently tease apart the cryptic diversity in this widely ranging springsnail. The new species described herein are narrowly distributed and vulnerable to anthropogenic stressors. The single known population of Pyrgulopsis torrida may have become extirpated between 2000 and 2015. PMID- 27551185 TI - Cheiracanthium ilicis sp. n. (Araneae, Eutichuridae), a novel spider species associated with Holm Oaks (Quercus ilex). AB - We describe a novel species Cheiracanthium ilicis sp. n. (Araneae, Eutichuridae) collected in the province of Toledo (Central Spain). It was found during a systematic sampling campaign carried out in an agricultural landscape with isolated Holm oaks Quercus ilex and small forest patches. Its morphology and affinities with other species of the genus are discussed. Furthermore, one mitochondrial gene was sequenced to confirm species membership and its differentiation from other Cheiracanthium species. The molecular phylogenies based on mitochondrial and nuclear genes showed a close relationship of Cheiracanthium ilicis sp. n. with Cheiracanthium inclusum and Cheiracanthium mildei, with which it also shares morphological similarities. Nonetheless, the sparse sampling of the phylogeny, due to the low number of sequences available, impedes drawing any definitive conclusion about these relationships; it is first necessary to perform an extensive review of the genus worldwide and more thorough phylogenies. Cheiracanthium ilicis sp. n. also shares certain ecological and phenological characteristics with Cheiracanthium inclusum and Cheiracanthium mildei. Like them, Cheiracanthium ilicis sp. n. is an obligate tree dweller that prefers a tree canopy habitat and reproduces primarily in late spring and summer. From a conservation perspective, the present study suggests the need to preserve isolated trees in agricultural landscapes. They are not only the refuge of common forest organisms but also of novel species yet to be discovered. PMID- 27551186 TI - First description of the male of Draconarius jiangyongensis (Peng et al., 1996) (Araneae, Agelenidae). AB - The male of Draconarius jiangyongensis (Peng, Gong & Kim, 1996) is described for the first time from Xinning County, Hunan Province, China. Morphological descriptions and illustrations of both sexes of this species are given in this study. The placement of this species in Draconarius is doubted. PMID- 27551187 TI - Nine new species of the spider genus Pireneitega Kishida, 1955 (Agelenidae, Coelotinae) from Xinjiang, China. AB - Nine new Pireneitega species collected from Xinjiang, China are described as new to science: Pireneitega burqinensis sp. n. (??), Pireneitega fuyunensis sp. n. (??), Pireneitega gongliuensis sp. n. (??), Pireneitega huochengensis sp. n. (??), Pireneitega lini sp. n. (?), Pireneitega liui sp. n. (??), Pireneitega wensuensis sp. n. (?), Pireneitega wui sp. n. (?) and Pireneitega yaoi sp. n. (?). DNA barcodes were obtained for all these species for future use. PMID- 27551188 TI - A further study of the spider genus Notiocoelotes (Araneae, Agelenidae) from Hainan Island, China. AB - Two new Notiocoelotes species, Notiocoelotes maoganensis sp. n. (??) and Notiocoelotes qiongzhongensis sp. n. (??) are described from Hainan Island, China. In addition, the female of Notiocoelotes membranaceus Liu & Li, 2010 is described for the first time. DNA barcodes of three species treated in this paper were obtained for future use. PMID- 27551189 TI - Kankuamo, a new theraphosid genus from Colombia (Araneae, Mygalomorphae), with a new type of urticating setae and divergent male genitalia. AB - A new monotypic Theraphosidae genus, Kankuamo Perafan, Galvis & Perez-Miles, gen. n., is described from Colombia, with a new type of urticating setae. These setae differ from others principally by having a small distal oval patch of lanceolate reversed barbs. Males of Kankuamo gen. n. additionally differ by having a palpal bulb organ very divergent from all known species, with many conspicuous keels dispersed across the median tegulum to the tip, mostly with serrated edges. Females differ by having spermathecae with a single notched receptacle, with two granulated lobes and several irregular sclerotized longitudinal striations. The new urticating setae, type VII, is characterized, illustrated and its releasing mechanism is discussed. It is hypothesized that these setae are the first in Theraphosinae subfamily whose release mechanism is by direct contact. Kankuamo gen. n. is described and illustrated on the basis of the type species Kankuamo marquezi Perafan, Galvis & Gutierrez, sp. n., and their remarkable characteristics, morphological affinities and cladistic relationship are analyzed. PMID- 27551190 TI - The first record of the millipede genus Streptogonopus Attems, 1914 from Vietnam, with description of a new species (Diplopoda, Polydesmida, Paradoxosomatidae). AB - This paper describes a new species of the millipede genus Streptogonopus Attems, 1914, Streptogonopus montanus sp. n. from Vietnam, the first record of Streptogonopus in Vietnam. The new species is characterised by the solenophore completely sheathing the solenomere, both coiled twice, and the solenophore with a small spine at its middle. The species was found at ca. 1,800-2,100 m on Ngoc Linh Mountain. This first record for the genus in the Indochina peninsula has expanded its distributional range to the easternmost part of Southeast Asian mainland. An identification key to Streptogonopus species is also provided. PMID- 27551191 TI - Description of a new species of Pseudomegischus van Achterberg from China (Hymenoptera, Stephanidae). AB - A new species of the genus Pseudomegischus van Achterberg, Pseudomegischus yunnanensis sp. n., is described and illustrated from Yunnan Province, China. This is the second species of the genus reported from China. A modified section of the identification key to species of Pseudomegischus is added to include the new species. PMID- 27551193 TI - A nomenclator of extant and fossil taxa of the Melanopsidae (Gastropoda, Cerithioidea). AB - This nomenclator provides details on all published names in the family-, genus-, and species-group, as well as for a few infrasubspecific names introduced for, or attributed to, the family Melanopsidae. It includes nomenclaturally valid names, as well as junior homonyms, junior objective synonyms, nomina nuda, common incorrect subsequent spellings, and as far as possible discussion on the current status in taxonomy. The catalogue encompasses three family-group names, 79 genus group names, and 1381 species-group names. All of them are given in their original combination and spelling (except mandatory corrections requested by the Code), along with their original source. For each family- and genus-group name, the original classification and the type genus and type species, respectively, are given. Data provided for species-group taxa are type locality, type horizon (for fossil taxa), and type specimens, as far as available. PMID- 27551192 TI - A review of the Japanese species of the family Tischeriidae (Lepidoptera). AB - This paper provides taxonomic and biological data on one new and one newly recorded species of Coptotriche Walsingham and one new and one newly recorded species of Tischeria Zeller from Japan. Coptotriche symplocosella Kobayashi & Hirowatari, sp. n. (host Symplocos lucida, Symplocaceae), and Tischeria kumatai Sato, Kobayashi & Hirowatari, sp. n. (host Tilia japonica, Malvaceae) are described. The pupal morphology of Coptotriche symplocosella is illustrated with scanning electron micrographs. Coptotriche minuta Diskus & Stonis, 2014 and Tischeria relictana Ermolaev, 1986 are newly recorded from Japan. The female, hostplants (Carpinus, Corylus, and Ostrya species), and immature stages of Coptotriche minuta and the adult features, female, and hostplants (Betula species) of Tischeria relictana are described with photographs and drawings for the first time. Mine types and characters of Japanese Tischeriidae are reviewed with photographs. PMID- 27551194 TI - A new Maldane species and a new Maldaninae genus and species (Maldanidae, Annelida) from coastal waters of China. AB - Paramaldane, new genus, with type species Paramaldane glandicincta sp. n., and Maldane adunca sp. n. (Maldanidae, Polychaeta) are described based on material from the coast of south China. The new genus Paramaldane is similar to Maldane Grube, 1860 and Sabaco Kinberg, 1867, but it clearly differs from all genera within the subfamily Maldaninae by a unique combination of characters: the cephalic plate is almost circular with low, entire and smooth cephalic rim, nuchal grooves small and crescentic, lacking a collar on chaetiger 1, short companion notochaetae, a collar-like glandular band on the anterior part of the sixth chaetiger, and a well-developed anal valve. Paramaldane glandicincta sp. n. is characterised by having a glandular band on the anterior part of the sixth chaetiger, an almost circular cephalic plate, an entire and smooth cephalic rim, and small crescentic nuchal grooves. Maldane adunca sp. n. is characterised by a low cephalic rim, nuchal grooves with a strongly curved anterior part and isolated from the cephalic rim. Finally, a taxonomic key to genera of Maldaninae and a comparative table to species of Maldane are provided. PMID- 27551195 TI - Conflict of mitochondrial phylogeny and morphology-based classification in a pair of freshwater gastropods (Caenogastropoda, Truncatelloidea, Tateidae) from New Caledonia. AB - Morphological classification and mitochondrial phylogeny of a pair of morphologically defined species of New Caledonian freshwater gastropods, Hemistomia cockerelli and Hemistomia fabrorum, were incongruent. We asked whether these two nominal species can be unambiguously distinguished based on shell morphology or whether the taxonomic discrepancy inferred from these character types was reflected in the variation of shell morphology. Our investigations were based on phylogenetic analyses of a fragment of the mitochondrial cytochrome c oxidase subunit I, geometric morphometric analyses as well as micro computer tomography. The species presorted to morphospecies by eye overlapped in shell shape. However, statistically, all shells were correctly assigned, but not all of them significantly. Qualitatively, both nominal species can be unambiguously distinguished by the presence/absence of a prominent denticle within the shell. In the phylogenetic analyses, individuals from three populations clustered with the "wrong" morphospecies. In the absence of data from multiple loci, it was assumed for the single specimen from one of these populations that its misplacement was due to a recent hybridization event, based on its very shallow position in the tree. For the other two cases of misplacement neither introgression nor incomplete lineage sorting could be ruled out. Further investigations have to show whether the morphological overlap has a genetic basis or is due to phenotypic plasticity. In conclusion, despite their partly unresolved relationships Hemistomia cockerelli and Hemistomia fabrorum may be considered sister species, which are reliably diagnosable by the presence or absence of the denticle, but have not yet fully differentiated in all character complexes investigated. PMID- 27551196 TI - Taxonomic evaluation of eleven species of Microcyclops Claus, 1893 (Copepoda, Cyclopoida) and description of Microcyclops inarmatus sp. n. from America. AB - Description and meristic analysis of eleven species of Microcyclops recorded in America were performed based on the examination of type specimens and fresh material. Microscopic analysis of oral appendages, such as the shape and armature of the distal coxal endite of the maxilla, the ornamentation on the caudal surface of the antenna, and the intercoxal sclerites and armament of the inner basis of all swimming appendages, were characteristics that allowed the differentiation between species. Among these species, our study confirmed the synonymy of Microcyclops diversus Kiefer, 1935 with Microcyclops ceibaensis (Marsh, 1919). The results of our observations showed that Microcyclops alius (Kiefer, 1935) is a junior synonym of Microcyclops dubitabilis Kiefer, 1934; the latter being confirmed as a valid species. Also, it is proposed that the records of Microcyclops rubellus (Lilljeborg, 1901) and Microcyclops varicans (Sars, 1863) in America should be revised as there are serious doubts about their distribution in America. The analysis suggested that Microcyclops anceps pauxensis Herbst, 1962 is distinct from Microcyclops anceps var. minor Dussart, 1984 and that both are likely different from Microcyclops anceps anceps (Richard, 1897). Finally a full morphological description of adult females of Microcyclops inarmatus sp. n. is presented. PMID- 27551197 TI - Two new species of Pachylaelaps Berlese, 1888 from the Iberian Peninsula, with a key to European species (Acari, Gamasida, Pachylaelapidae). AB - Pachylaelaps (Pachylaelaps) pyrenaicus sp. n. and Pachylaelaps (Longipachylaelaps) brevipilis sp. n. (Acari, Pachylaelapidae) are described and illustrated based on specimens from litter and soil detritus of forest habitats in Spain (Pyrenees Mts) and Portugal (Serra da Labruja Mts), respectively. An identification key to European species of the genus Pachylaelaps Berlese, 1888 is provided. PMID- 27551198 TI - Fangumellus flavobadius: a new genus and species of plant bug from Laos (Heteroptera, Miridae, Mirinae, Mirini). AB - A new species of the plant bug tribe Mirini representing a new genus, Fangumellus flavobadius, is described from Laos. This genus is characterized primarily by the medium-sized, ovoid, tumid body, less shiny, roughened, almost impunctate dorsal surface, short antenna and labium, short pygophore, and atypical shape of parameres and endosoma. The phylogenetic relationship to other known mirine genera is also discussed. PMID- 27551199 TI - Taxonomic revision of the Malagasy Nesomyrmex madecassus species-group using a quantitative morphometric approach. AB - Here we reveal the diversity of the next fragment of the Malagasy elements of the ant genus Nesomyrmex using a combination of advanced exploratory analyses on quantitative morphological data. The diversity of the Nesomyrmex madecassus species-group was assessed via hypothesis-free nest centroid clustering combined with recursive partitioning to estimate the number of clusters and determine the most probable boundaries between them. This combination of methods provides a highly automated species delineation protocol based on continuous morphometric data, and thereby it obviates the need of subjective interpretation of morphological patterns. Delimitations of clusters recognized by these exploratory analyses were tested via confirmatory Linear Discriminant Analysis (LDA). Our results suggest the existence of four morphologically distinct species, Nesomyrmex flavus sp. n., Nesomyrmex gibber, Nesomyrmex madecassus and Nesomyrmex nitidus sp. n.; all are described here and an identification key for their worker castes using morphometric data is given. Two members of the newly outlined madecasus species-group, Nesomyrmex flavus sp. n. and Nesomyrmex nitidus sp. n., represent true cryptic species. Geographic maps depicting species distributions and elevational information for the sites where populations of particular species were collected are also provided. PMID- 27551200 TI - New Brazilian Cerambycidae from the Amazonian region (Coleoptera). AB - Three new species of Cerambycidae are described from the Brazilian Amazonian region: Psapharochrus bezarki (Lamiinae, Acanthoderini); Xenofrea ayri (Lamiinae, Xenofreini); and Mecometopus wappesi (Cerambycinae, Clytini). Mecometopus wappesi is added to a previous key. PMID- 27551201 TI - Morphology and development rate of the immature stages of Glyphidops (Oncopsia) flavifrons (Bigot, 1886) (Diptera, Neriidae) under natural conditions. AB - Of the 116 Neriidae species known to date, 113 species have not been studied in their immature stages. Here, we examine the development of the immature stages of Glyphidops (Oncopsia) flavifrons (Bigot, 1886), which has one of the broadest distributions of Neriidae in southern North America, Central America, and South America; offering excellent opportunities for biological studies. A population of this species was monitored over a five month period. The following characteristics were tracked for a population located on the University of Valle campus in Cali, Colombia: oviposition duration, number of eggs per egg mass and lifespan of each immature stage (egg, larva, and puparium) under natural conditions (in situ). The external morphology of the egg, larva, and puparium were described; their stages lasted 58 (+/- 4) hours, 10 (+/- 1) days and 13 (+/- 1) days, respectively. The lapse of time for each larval instar was statistically supported by using Tukey comparisons and cluster analysis of hypopharyngeal sclerite length and mandibular area. In addition, it was also sustained throughout the morphological study of structural changes in mouth hook, and anterior and posterior spiracles. Finally, the presence of the labial and epipharyngeal sclerites are reported as new characters of Nerioidea. Natural history data are provided. PMID- 27551202 TI - Psallops niedzwiedzkii, a new species from Ghana with a key to African species (Heteroptera, Miridae, Psallopinae). AB - A new species from Ghana, Psallops niedzwiedzkii Herczek & Popov, sp. n. is described. The dorsal habitus, head and male genitalia are presented and some morphological features are discussed. A key, short descriptions and map of the distribution of the African species of the genus are also provided. PMID- 27551203 TI - Paracerella Imadate in China: the description of a new species and the analysis of genetic differences between populations (Protura, Acerentomata, Nipponentomidae). AB - The genus Paracerella Imadate, 1980 is recorded from China for the first time, with the description of a new species, Paracerella sinensis sp. n. Paracerella sinensis is characterized by four pairs of A-setae on tergite I, the presence of setae Pc and P3a on tergite VII, eight A-setae on tergite VIII, the presence of seta Pc on both sternites VI and VII, and 4/2 setae on sternite VIII, which are different from all other members of the genus. The key to the four species of the genus is updated. In addition, DNA barcodes of four populations are sequenced and their genetic differences are analyzed. PMID- 27551204 TI - Atlanta ariejansseni, a new species of shelled heteropod from the Southern Subtropical Convergence Zone (Gastropoda, Pterotracheoidea). AB - The Atlantidae (shelled heteropods) is a family of microscopic aragonite shelled holoplanktonic gastropods with a wide biogeographical distribution in tropical, sub-tropical and temperate waters. The aragonite shell and surface ocean habitat of the atlantids makes them particularly susceptible to ocean acidification and ocean warming, and atlantids are likely to be useful indicators of these changes. However, we still lack fundamental information on their taxonomy and biogeography, which is essential for monitoring the effects of a changing ocean. Integrated morphological and molecular approaches to taxonomy have been employed to improve the assessment of species boundaries, which give a more accurate picture of species distributions. Here a new species of atlantid heteropod is described based on shell morphology, DNA barcoding of the Cytochrome Oxidase I gene, and biogeography. All specimens of Atlanta ariejansseni sp. n. were collected from the Southern Subtropical Convergence Zone of the Atlantic and Indo Pacific oceans suggesting that this species has a very narrow latitudinal distribution (37-48 degrees S). Atlanta ariejansseni sp. n. was found to be relatively abundant (up to 2.3 specimens per 1000 m(3) water) within this narrow latitudinal range, implying that this species has adapted to the specific conditions of the Southern Subtropical Convergence Zone and has a high tolerance to the varying ocean parameters in this region. PMID- 27551206 TI - Description of a new species of Metabemisia Takahashi, 1963 from China (Hemiptera, Aleyrodidae). AB - A new whitefly species, Metabemisia leguminosa sp. n., collected from an undetermined leguminous herb is described from Wuzhishan Mountain, Hainan Island, China. The puparium of the new species differs from that of all other Metabemisia species by the presence of 4-5 rows of very small distinct papillae along the margin, the absence of the first abdominal seta, and the indistinct thoracic tracheal pores. An identification key to the worldwide species of Metabemisia is provided. PMID- 27551205 TI - New blind species and new records of Sinella from Nanjing, China (Collembola, Entomobryidae). AB - Two new blind species of Sinella are described from Nanjing, China. Sinella quinseta sp. n. from Purple Mountain possesses unique 5+5 central macrochaetae on Abd. II, and can be distinguished from other species of the genus by the postlabial chaetae and the dorsal chaetotaxy. Sinella qixiaensis sp. n. from Qixia Mountain is characterized by the paddle-like S-chaetae of Ant. III organ and the smooth straight chaetae on the manubrium and base of dens; it differs from two closely related species by the smooth manubrial chaetae, the labial chaetae, the Ant. III organ, and the macrochaetae on Abd. II. Sinella fuyanensis Chen & Christiansen and Sinella quinocula Chen & Christiansen were also newly recorded from Nanjing. PMID- 27551207 TI - A revision of the genus Pseudoechthistatus Pic (Coleoptera, Cerambycidae, Lamiinae, Lamiini). AB - The genus Pseudoechthistatus Pic, 1917 is redefined and revised. Five species of the genus are described as new, Pseudoechthistatus sinicus sp. n. and Pseudoechthistatus chiangshunani sp. n. from central Yunnan, China, Pseudoechthistatus pufujiae sp. n. from western Yunnan, China, and Pseudoechthistatus holzschuhi sp. n. and Pseudoechthistatus glabripennis sp. n. from southern Yunnan and northern Vietnam. Pseudoechthistatus birmanicus Breuning, 1942 is excluded from the fauna of China. Three poorly known species, Pseudoechthistatus obliquefasciatus Pic, 1917, Pseudoechthistatus granulatus Breuning, 1942, and Pseudoechthistatus acutipennis Chiang, 1981 are redescribed, and the type localities of the former two species are discussed. Endophallic structure of seven species in inflated and everted condition are studied and compared with their relatives. Illustrations of habitus and major diagnostic features of all species are provided. Some biological notes are reported. An identification key as well as a distributional map are presented. PMID- 27551208 TI - The morphology of the immature stages of two rare Lixus species (Coleoptera, Curculionidae, Lixinae) and notes on their biology. AB - The mature larvae and pupae of Lixus (Ortholixus) bituberculatus Smreczynski, 1968 and Lixus (Dilixellus) neglectus Fremuth, 1983 (Curculionidae: Lixinae: Lixini) are described and compared with known larvae of 21 other Lixus and 2 Hypolixus taxa. The mature larva and pupa of Lixus bituberculatus are the first immature stages described representing the subgenus Ortholixus. The larva of Lixus neglectus, in the subgenus Dilixellus, is distinguished from the known larvae of four species in this subgenus by having more pigmented sclerites on the larval body. All descriptions of mature larvae from the tribe Lixini, as do all known species from the tribe Cleonini, fit the diagnosis of the mature larva of the Lixinae subfamily. Furthermore, new biological information of these species in the Czech Republic, Slovakia and Romania is provided. For Lixus bituberculatus, a chicory, Cichorium intybus L. (Asteraceae), is identified as a host plant, and Lixus neglectus is found on dock Rumex thyrsiflorus Fingerh. (Polygonaceae). Both species are probably monophagous or oligophagous. Adults of Lixus bituberculatus often inhabit host plants growing in active, dry and sunny pastures with sparse patches without vegetation, being mostly active during the night in April/May and then again in September, when the highest activity levels are observed. Adults of Lixus neglectus inhabit dry grasslands on sandy soils with host plants, being active during the day from May to September, with the highest level of activity in May/June and September. The larvae of both species are borers in the stem and root of the host plant, and they pupate in root or root neck. Adults leave the pupation cells at the end of summer and do not hibernate in the host plants. Finally, Romania is a new geographic record for Lixus bituberculatus. PMID- 27551209 TI - New species of Medetera from Inner Mongolia, China (Diptera, Dolichopodidae, Medeterinae). AB - Only three species of Medetera Fischer von Waldheim were known from Inner Mongolia. Here the following ten new species of Medetera, of which three species belong to Medetera apicalis group and seven belong to Medetera diadema-veles group, are added to the fauna of Inner Mongolia: Medetera albens sp. n., Medetera bisetifera sp. n., Medetera flava sp. n., Medetera ganshuiensis sp. n., Medetera lihuae sp. n., and Medetera transformata sp. n., Medetera triseta sp. n., Medetera shiae sp. n., Medetera shuimogouensis sp. n., and Medetera xiquegouensis sp. n. A key to the species of Medetera from Palaearctic China is provided. PMID- 27551210 TI - Phylogenetic relationships within the Phyllidiidae (Opisthobranchia, Nudibranchia). AB - The Phyllidiidae (Gastropoda, Heterobranchia, Nudibranchia) is a family of colourful nudibranchs found on Indo-Pacific coral reefs. Despite the abundant and widespread occurrence of many species, their phylogenetic relationships are not well known. The present study is the first contribution to fill the gap in our knowledge on their phylogeny by combining morphological and molecular data. For that purpose 99 specimens belonging to 16 species were collected at two localities in Indonesia. They were photographed and used to make a phylogeny reconstruction based on newly obtained cytochrome oxidase subunit (COI) sequences as well as sequence data from GenBank. All mitochondrial 16S sequence data available from GenBank were used in a separate phylogeny reconstruction to obtain information for species we did not collect. COI data allowed the distinction of the genera and species, whereas the 16S data gave a mixed result with respect to the genera Phyllidia and Phyllidiella. Specimens which could be ascribed to species level based on their external morphology and colour patterns showed low variation in COI sequences, but there were two exceptions: three specimens identified as Phyllidia cf. babai represent two to three different species, while Phyllidiella pustulosa showed highly supported subclades. The barcoding marker COI also confirms that the species boundaries in morphologically highly variable species such as Phyllidia elegans, Phyllidia varicosa, and Phyllidiopsis krempfi, are correct as presently understood. In the COI as well as the 16S cladogram Phyllidiopsis cardinalis was located separately from all other Phyllidiidae, whereas Phyllidiopsis fissuratus was positioned alone from the Phyllidiella species by COI data only. Future studies on phyllidiid systematics should continue to combine morphological information with DNA sequences to obtain a clearer insight in their phylogeny. PMID- 27551211 TI - A new species of Nebalia (Crustacea, Leptostraca) from coral reefs at Pulau Payar, Malaysia. AB - A new species of Leptostraca, Nebalia terazakii sp. n. is described and figured. The species was sampled from the coral reefs of Pulau Payar Marine Park, Langkawi, Malaysia. There are 32 existing species of Nebalia but Nebalia terazakii sp. n. can be distinguished from the other known species of Nebalia by the following combination of characters: the rostrum is 1.89 times as long as wide and the eyes have no dorsal papilla or lobes. Article 4 of the antennular peduncle has one short thick distal spine. The proximal article of the endopod of maxilla 2 is shorter than the distal, a feature peculiar to Nebalia terazakii sp. n., the exopod of maxilla 2 is longer than article 1 of the endopod, the posterior dorsal borders of the pleonites 6 to 7 are provided with distally sharp denticles, anal plate with prominent lateral shoulder and finally, the terminal seta of the caudal rami is 1.17 times the length of the entire rami. PMID- 27551212 TI - The first geophilid centipedes from Malesia: a new genus with two new species from Sumatra (Chilopoda, Geophilidae). AB - A new genus Sundageophilus is here described for two new species of geophilid centipedes (Chilopoda: Geophilidae) from Sumatra, Indonesia. Both Sundageophilus bidentatus sp. n. and Sundageophilus poriger sp. n. feature a minute body size (less than 1 cm long with 31-35 pairs of legs), a similar structure of the maxillae, elongated forcipules, and few coxal organs. Sundageophilus bidentatus is unique among geophilids because the ultimate article of the forcipule is armed with two conspicuous denticles, one dorsal to the other, instead of a single one or none. The two species of Sundageophilus are the first genuine Geophilidae ever found in Malesia, and among the very few representatives of this family in the entire south-eastern Asia. PMID- 27551213 TI - Geographic distribution of Gryllotalpa stepposa in south-eastern Europe, with first records for Romania, Hungary and Serbia (Insecta, Orthoptera, Gryllotalpidae). AB - Described from the steppe zones north of the Black Sea, Caucasus, and central Asia, Gryllotalpa stepposa Zhantiev was recently recorded from a few localities in Greece, R. Macedonia, and Bulgaria. In May 2015, several specimens were collected from Ivrinezu Mare in Romania, which suggested a continuous distribution area of the species, stretching from the central Balkans to central Asia. Thus, to reveal its actual range of occurrence, a survey of several Orthoptera collections became mandatory and, as expected, a large number of misidentified specimens of Gryllotalpa stepposa were discovered, providing new data on the species distribution in south-eastern Europe, including also the first records of this mole cricket in Serbia and Hungary. Here a full locality list is presented of this species west of Ukraine and Moldova and the current geographic distribution of the genus Gryllotalpa in the Balkans is revised. A key for distinguishing the mole crickets in south-eastern Europe and a distribution map for this region are presented. PMID- 27551214 TI - A new species of Octaspidiotus (Hemiptera, Diaspididae) from China. AB - Adult females of a new species of armored scale insect, Octaspidiotus shanghaiensis sp. n. are described and illustrated from specimens collected in China. A key is provided for the all described species of Octaspidiotus. PMID- 27551215 TI - First description of the male of Hiranetis atra Stal and new country records, with taxonomic notes on other species of Hiranetis Spinola (Hemiptera, Heteroptera, Reduviidae, Harpactorinae). AB - The male of Hiranetis atra Stal, 1872 is described and illustrated for the first time. In addition, this paper illustrates the female and provides new country records for this species. Photographs of all extant types of species of Hiranetis Spinola, 1840 are presented with taxonomic notes on the other two species of the genus. PMID- 27551216 TI - Socially-parasitic Myrmica species (Hymenoptera, Formicidae) of Himalaya, with the description of a new species. AB - A new socially-parasitic species, Myrmica latra sp. n. is described based on a queen and male from Indian Himalaya. Its queen differs from other species by the distinctly narrower petiole and postpetiole, blunt and non-divergent propodeal spines, and a darker body colour. The taxonomic position of the three known Himalayan socially-parasitic Myrmica species is discussed, and Myrmica ereptrix Bolton 1988 is transferred to the smythiesii species-group. It is supposed that Myrmica nefaria Bharti 2012 is a temporary social parasite, but Myrmica ereptrix and Myrmica latra sp. n. are permanent social parasites, and a key for their identification is provided. PMID- 27551217 TI - Mulloidichthys flavolineatus flavicaudus Fernandez-Silva & Randall (Perciformes, Mullidae), a new subspecies of goatfish from the Red Sea and Arabian Sea. AB - The number of goatfish species has increased recently, thanks in part to the application of molecular approaches to the taxonomy of a family with conservative morphology and widespread intraspecific color variation. A new subspecies Mulloidichthys flavolineatus flavicaudus Fernandez-Silva & Randall is described from the Red Sea and Arabian Sea, including Socotra and Gulf of Oman. It is characterized by a yellow caudal fin, 25-28 gill rakers, and 37-38 lateral-line scales and it is differentiated from nominal subspecies Mulloidichthys flavolineatus flavolineatus by 1.7% sequence divergence at the mitochondrial cytochrome b gene. The morphometric examination of specimens of Mulloidichthys flavolineatus flavolineatus revealed variation in head length, eye diameter, and barbel length, in western direction from the Hawaiian Islands, South Pacific, Micronesia, and the East Indies to the Indian Ocean. The population of Mulloidichthys flavolineatus flavicaudus subsp. n. in the Gulf of Aqaba differs from that of the remaining Red Sea by shorter barbels, smaller eyes, shorter head, and shorter pelvic fins. We present a list of 26 endemic fishes from the Gulf of Aqaba and discuss the probable basis for the endemism in the light of the geological history of this region. PMID- 27551218 TI - Epiphytic bryozoans on Neptune grass - a sample-based data set. AB - BACKGROUND: The seagrass Posidonia oceanica L. Delile, commonly known as Neptune grass, is an endemic species of the Mediterranean Sea. It hosts a distinctive and diverse epiphytic community, dominated by various macroalgal and animal organisms. Mediterranean bryozoans have been extensively studied but quantitative data assessing temporal and spatial variability have rarely been documented. In Lepoint et al. (2014a, b) occurrence and abundance data of epiphytic bryozoan communities on leaves of Posidonia oceanica inhabiting Revellata Bay (Corsica, Mediterranean Sea) were reported and trophic ecology of Electra posidoniae Gautier assessed. NEW INFORMATION: Here, metadata information is provided on the data set discussed in Lepoint et al. (2014a) and published on the GBIF portal as a sampling-event data set: http://ipt.biodiversity.be/resource?r=ulg_bryozoa&v=1.0). The data set is enriched by data concerning species settled on Posidonia scales (dead petiole of Posidonia leaves, remaining after limb abscission). PMID- 27551219 TI - A new solitary free-living species of the genus Sphenopus (Cnidaria, Anthozoa, Zoantharia, Sphenopidae) from Okinawa-jima Island, Japan. AB - A new species of free-living solitary zoantharian is described from Okinawa, Japan. Sphenopus exilis sp. n. occurs on silty seafloors in Kin Bay and Oura Bay on the east coast of Okinawa-jima Island. Sphenopus exilis sp. n. is easily distinguished from other Sphenopus species by its small polyp size and slender shape, although there were relatively few differences between Sphenopus exilis sp. n. and Sphenopus marsupialis in the molecular phylogenetic analyses. Currently, very little is known about the ecology and diversity of Sphenopus species. Thus, reviewing each species carefully via combined morphological and molecular analyses by using newly obtained specimens from type localities is required to clearly understand and distinguish the species within the genus Sphenopus. PMID- 27551220 TI - Revision of the genus Paralipsis Foerster, 1863 (Hymenoptera, Braconidae), with the description of two new species. AB - The Palaearctic genus Paralipsis Foerster, 1863 (Hymenoptera: Braconidae: Aphidiinae) is revised and two new species are described: Paralipsis tibiator van Achterberg & Ortiz de Zugasti, sp. n. from Spain and Paralipsis planus van Achterberg, sp. n. from the Netherlands. Some biological notes are supplied for Paralipsis tibiator sp. n. A key to the four known species is added and all species are illustrated. PMID- 27551221 TI - New data on distribution, biology, and ecology of longhorn beetles from the area of west Tajikistan (Coleoptera, Cerambycidae). AB - New data on distribution, biology, and ecology of some little-known cerambycid species, collected in the western part of Tajikistan, are presented. Arhopalus rusticus (Linnaeus, 1758) is recorded in Tajikistan for the first time. New localities of species considered pests or invasive species such as Aeolesthes sarta (Solsky, 1871) and Xylotrechus stebbingi Gahan, 1906 are also given. The list of the taxa collected by the first author during many years of field research in Tajikistan as well as photographs of poorly known species from his collection, including some endemics, are additionally provided. Furthermore, high quality photographs of some extremely rare species that were collected during our expedition, i.e., Turkaromia gromenkoi Danilevsky, 2000 and Ropalopus nadari Pic, 1894, with images of their habitats or feeding grounds are also presented for the first time. PMID- 27551222 TI - First Maltese record of Stephanopachys quadricollis (Marseul, 1879) (Coleoptera, Bostrichidae). AB - Three specimens of Stephanopachys quadricollis (Marseul, 1878) were recently found in Malta in UV light traps and represent the first record of this species for this country. Although Stephanopachys quadricollis is native to the Mediterranean basin, it is not yet clear if these Maltese records are due to a natural population or to an interception. Distributional, nomenclatural and biological data on this species are summarized, and a new synonymy is established: Stephanopachys quadricollis (Marseul, 1879) = Stephanopachys quadraticollis Kocher, 1956, syn. n. PMID- 27551223 TI - A new species of Pristimantis from southern Ecuador (Anura, Craugastoridae). AB - A new species of Pristimantis is described from Reserva Buenaventura, southern Ecuador, at elevations between 878 and 1082 m. A molecular phylogeny based on nuclear and mitochondrial genes shows that the new species is closely related to Pristimantis phoxocephalus, Pristimantis riveti, and Pristimantis versicolor. The new species differs from them and other morphologically similar congeners in having a low W-shaped dermal ridge in the scapular region, a large conical tubercle on the upper eyelid and on the heel, a thin mid dorsal fold, and a longitudinal lateral fold starting behind the tympanic fold and extending along the anterior two thirds of the flank. The new species inhabits cloud forests in the Pacific slopes of the Andes. PMID- 27551224 TI - Annotated checklist of the coastal ichthyofauna from Michoacan State, Mexico. AB - This study is the first to complete an intensive and comprehensive list of the ichthyofauna of nearly all ecosystems of the Michoacan coast, Mexico. The resulting systematic checklist, supplemented with information from the literature and scientific collections, comprises 440 species belonging to two classes, 31 orders, 104 families, and 264 genera. The families with the highest number of species were Sciaenidae (30 spp.), Carangidae (26), Haemulidae (24), Serranidae (21), Paralichthyidae, and Gobiidae (13). Of the total species list, 134 represent first records for the Michoacan State, and one is a first record for Mexico. The results expand the number of known fish species of the Michoacan coast by almost one third and will help to develop conservation and management plans for this coastal zone. PMID- 27551225 TI - An inventory of coastal freshwater fishes from Amapa highlighting the occurrence of eight new records for Brazil. AB - The Amazon Basin occupies a vast portion of northern South America and contains some of the highest species richness in the world. The northern Brazilian state of Amapa is delimited by the Amazonas River to the south, the Oyapock River to the northern boundary with French Guyana, and the Atlantic northeastern coast to Amazon estuary. Despite several expeditions to the Amazon in recent decades, little is known about the freshwater ichthyofauna from Amapa, with records limited to local inventories and species descriptions. This paper presents a compilation of the freshwater fish diversity sampled in fifteen sites covering two major Amapa ecoregions during the dry season of 2015. 120 species representing eight orders and 40 families are reported upon in this work. Eight species appear for the first time in the Brazilian territory providing new information for future conservation status evaluations. PMID- 27551227 TI - Eleven nominal species of Burmoniscus are junior synonyms of B. kathmandius (Schmalfuss, 1983) (Crustacea, Isopoda, Oniscidea). AB - Holotypes, paratypes, and specimens newly collected from the type localities (i.e., topotypes) of Burmoniscus aokii (Nunomura, 1986), Burmoniscus boninensis (Nunomura, 1986), Burmoniscus daitoensis (Nunomura, 1986), Burmoniscus hachijoensis Nunomura, 2007, Burmoniscus japonicus (Nunomura, 1986), Burmoniscus kagoshimaensis Nunomura, 2003, Burmoniscus murotoensis (Nunomura, 1986), Burmoniscus okinawaensis (Nunomura, 1986), Burmoniscus shibatai (Nunomura, 1986), Burmoniscus tanabensis Nunomura, 2003, and Burmoniscus watanabei (Nunomura, 1986) were examined in order to clarify their taxonomic status. Observation of 13 morphological characters that were purposed to show species-level diagnostic variations in the original descriptions suggests that all eleven nominal species are identical, and molecular analysis based on three gene fragments supports this suggestion. Additionally, the morphology of the carpus of pereopod 1 and of the endo- and exopodites of pleopod 1 of these species are consistent with those of Burmoniscus kathmandius (Schmalfuss, 1983). The eleven above-mentioned species of Burmoniscus described from Japan are therefore relegated to junior synonyms of Burmoniscus kathmandius, originally reported from Nepal. PMID- 27551226 TI - A new deep-reef scorpionfish (Teleostei, Scorpaenidae, Scorpaenodes) from the southern Caribbean with comments on depth distributions and relationships of western Atlantic members of the genus. AB - A new species of scorpionfish, Scorpaenodes barrybrowni Pitassy & Baldwin, sp. n. which is described, was collected during submersible diving in the southern Caribbean as part of the Smithsonian's Deep Reef Observation Project (DROP). It differs from the other two western Atlantic species of the genus, Scorpaenodes caribbaeus and Scorpaenodes tredecimspinosus, in various features, including its color pattern, having an incomplete lateral line comprising 8-10 pored scales, tending to be more elongate, usually having the 11(th)-12(th) pectoral-fin rays elongate, and by 20-23% divergence in the cytochrome c oxidase I (COI) DNA barcode sequences. It further differs from one or the other of those species in head spination and in numbers of soft dorsal-fin rays, pectoral-fin rays, and precaudal + caudal vertebrae. Inhabiting depths of 95-160 m, the new species is the deepest western Atlantic member of the genus (Scorpaenodes caribbaeus occurs at depths < 35 m and Scorpaenodes tredecimspinosus from 7 to 82 m). DNA barcode data do not rigorously resolve relationships among the ten species of the genus for which those data are available. PMID- 27551228 TI - A new species of the rare genus Priscomilitaris from the Seto Inland Sea, Japan (Crustacea, Amphipoda, Priscomilitaridae). AB - A new species of the priscomilitarid amphipod, Priscomilitaris heike, from the Seto Inland Sea, Japan, is named and described. This new species is the third species of Priscomilitaridae and the second species of Priscomilitaris. Additionally, nucleotide sequences of nuclear 28S rRNA and histone H3 as well as mitochondrial cytochrome c oxidase subunit I from its holotype were determined. Priscomilitaris heike sp. n. is distinguished from its congener, Priscomilitaris tenuis Hirayama, 1988, by having deep antennal sinus, long flagellar article 1 of antennae 1 and 2, long mandibular palp article 2, 10 robust setae on outer ramus of maxilla 1, and rounded epimeral plates. A key to the species of Proscomilitaridae is provided. PMID- 27551229 TI - The nymph and imago of Chinese mayfly Siphlonurus davidi (Navas, 1932). AB - The imagos and nymphs of Siphlonurus davidi (Navas, 1932) are described for the first time. The adult has colourful wings and cross veins, the MP is forked asymmetrically at its base, a long cubital area is present with more intercalaries, and it has a relatively simpler penis and larger hindwings compared to its congeners. The venation and genitalia show that it is a plesiomorphic species in the genus. A key to the Asian species of Siphlonurus with coloured wings is provided in conclusion. PMID- 27551230 TI - An updated list of type material of Ephemeroptera Hyatt & Arms, 1890, deposited at the Zoological Museum of Hamburg (ZMH). AB - The type specimens of Ephemeroptera (Insecta) housed at the Zoological Museum of Hamburg (ZMH) are compiled in this document. The current nomenclature of all species is given. In total, Ephemeroptera type material of ZMH encompasses 161 species. Fifty-one holotypes and five lectotypes are present. Forty-one species are represented by syntypes, 85 by paratypes and five by paralectotypes. Material of two species (Cinygma asiaticum Ulmer, 1924 and Pseudocloeon klapaleki Muller Liebenau, 1982) is missing. The present catalogue is an updated version of Weidner (1964a). PMID- 27551231 TI - A new species and a revised key of the genus Thoradonta (Orthoptera, Tetrigidae). AB - A new species of the genus Thoradonta (Orthoptera, Tetrigidae), Thoradonta varispina Zha & Sheng, sp. n., was found in Lengshuihe Nature Preserve, Jinsha, Guizhou, China. It is introduced with a description and photographs and compared with similar taxa. Ecology, habits, and morphological variation of the new species are discussed and illustrated. Generic characteristics of Thoradonta are updated and an updated key to all known species of Thoradonta is given. PMID- 27551232 TI - A review of Elocomosta Hansen with a description of a new species with reduced eyes from China (Coleoptera, Hydrophilidae, Sphaeridiinae). AB - A new species of the genus Elocomosta Hansen, 1989 (Coleoptera: Hydrophilidae: Sphaeridiinae: Coelostomatini), Elocomosta lilizheni sp. n., is described from Guangxi Province, China. It is compared in detail with the only other known species of the genus, Elocomosta nigra Hansen, 1989 from Borneo, and the genus is diagnosed from the remaining coelostomatine genera. The new species is unusual among Hydrophilidae by having extremely reduced eyes. PMID- 27551233 TI - A new species of Monocheres Stock (Copepoda, Siphonostomatoida, Asterocheridae) from shallow waters off Florida, USA: an unexpected discovery. AB - The rare asterocherid copepod genus Monocheres, ectosymbionts of corals and sponges, contains only two species, one from Mauritius (Indian Ocean) and the other one from Brazil (western Atlantic). From the analysis of the digestive caecum contents of the benthic hesionid polychaete Hesione picta Muller, 1858, an adult female of an undescribed species of Monocheres was unexpectedly recovered; it is the third species of this rare asterocherid genus. The new species, Monocheres sergioi sp. n., has the distinctive reduction of the fifth leg as a process with a single seta. It differs from its two other congeners by several characters including the presence of an inner basipodal spine, the armature details of the third exopodal segment of leg 1, the shape of the cephalosome and pedigerous somites 3 and 4, and the ornamentation of the postero-lateral corners of the genital double-somite. The main synapomorphies include the presence of spinules along the posterior margin of the first leg coxal sclerite and the reduced, spiniform coxal seta on leg 4. The biology and feeding habits of the polychaete containing this specimen suggests that the copepod was ingested as an ectosymbiont from sponges or coral but it is also possible that it was consumed from an ophiurid echinoderm. This finding allows an expansion of the genus geographical distribution in the northwestern Atlantic. A key to the species of Monocheres is also provided. PMID- 27551234 TI - Two new species and one newly recorded species of Uloma Dejean, 1821 from Zhejiang, China (Coleoptera, Tenebrionidae, Ulomini). AB - Two new species of the genus Uloma Dejean, 1821, Uloma fengyangensis sp. n. and Uloma acrodonta sp. n., are described and figured from Zhejiang Province of China. Uloma bonzica Marseul, 1876 is recorded from China for the first time. A key to the known Uloma species from Zhejiang of China and a list of Uloma species from China are provided. PMID- 27551235 TI - Revision of the genus Ptomaphagus Hellwig (Coleoptera, Leiodidae, Cholevinae) from Japan. AB - After examining Japanese material of Ptomaphagus Hellwig from various collections, a new species is described, Ptomaphagus (s. str.) piccoloi sp. n., and a new subjective synonym proposed, Ptomaphagus (s. str.) kuntzeni Sokolowski, 1957 = Ptomaphagus (s. str.) amamianus Nakane, 1963, syn. n., in this paper. Relevant morphological characters of examined species of Ptomaphagus are illustrated with colour plates, and known distributions are mapped. PMID- 27551236 TI - New replacement name for Chrysotus infirmus Wei, Zhang & Zhou, 2014 (Diptera, Dolichopodidae, Diaphorinae). AB - Chrysotus weii Zhou, nom. n., the new replacement name is proposed for the species Chrysotus infirmus Wei, Zhang & Zhou, 2014 (Diptera: Brachycera: Dolichopodidae: Diaphorinae), which was preoccupied by Chrysotus infirmus Parent, 1933. PMID- 27551237 TI - Development and utility of an in vitro, fluorescence-based assay for the discovery of novel compounds against dengue 2 viral protease. AB - BACKGROUND: Dengue disease is one of the most significant vector-borne illnesses in the world. The emergence and re-emergence of dengue infections in many parts of the world affect millions annually and continue to burden public health systems especially in low-income populations. Advances in dengue vaccine development showed promising results; however, protection seems to be suboptimal. There is no licensed chemotherapeutic agent against dengue to date. An ideal scenario of combinatorial vaccination of high-risk individuals and chemotherapy of the diseased during outbreaks may compensate for the meager protection offered by the vaccine. The dengue virus protease is important to viral replication and, as such, has been identified as a potential target for antivirals. It is, therefore, our objective to establish and optimize an appropriate screening method for use during the early stages of drug development for dengue. METHODS: In this study, we developed and optimized a biochemical assay system for use in screening compound libraries against dengue virus protease. We tested the selected protease inhibitors with a cell-based assay to determine inhibition of viral replication. RESULTS: We have presented direct plots of substrate kinetics data showing an apparent inhibition of the protease at excessive substrate concentrations. The most common sources of interference that may have affected the said observation were elucidated. Finally, a screen was done on an existing compound library using the developed method. The compounds selected in this study showed inhibitory activity against both the recombinant dengue protease and cell based infectivity assays. CONCLUSIONS: Our study shows the practicality of a customized biochemical assay to find possible inhibitors of dengue viral protease during the initial stages of drug discovery. PMID- 27551240 TI - Symptom Co-occurrences Associated with Smoking in Individuals with Relapsing Remitting Multiple Sclerosis. AB - BACKGROUND: The impact of tobacco on the multiple sclerosis (MS) disease process and symptoms is complex and not clearly understood. Tobacco may be used to self treat some symptoms but also seems to intensify others. Studies to date have not characterized co-occurring symptoms (symptom patterns) and their association with tobacco use. METHODS: This study describes tobacco use in patients with relapsing remitting MS and associated symptoms and symptom co-occurrences. In this cross sectional study, 101 participants with an average age of 43 years completed a survey adapted from the Behavioral Risk Factor Surveillance System and the revised MS-Related Symptom Checklist. Data reduction was performed using factor analysis on the 43 items of the checklist, and linear regression was used to detect associations between symptom clusters (factors) and smoking. RESULTS: Using the factor analysis result, the linear regression analysis found that tobacco use is positively associated with co-occurring symptoms and symptoms of factor 1: Mental/Emotional (anxiety, loneliness, depression, and difficulty sleeping) and factor 4: Neuro/Autonomic (urinary). CONCLUSIONS: Smoking is associated with patterns of symptoms. The study of MS and tobacco use over time will allow determination of the temporal pattern of tobacco use and MS symptoms. PMID- 27551238 TI - Iridotomy to slow progression of angle-closure glaucoma. AB - This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective is to assess the role of iridotomy-compared with observation-in the prevention of visual field loss for individuals who have primary angle closure or primary angle-closure glaucoma in at least one eye. We will also examine the role of iridotomy in the prevention of elevated intraocular pressure (IOP) in individuals with narrow angles (primary angle-closure suspect) in at least one eye. PMID- 27551241 TI - A Randomized Crossover Trial of Dalfampridine Extended Release for Effect on Ambulatory Activity in People with Multiple Sclerosis. AB - BACKGROUND: Dalfampridine extended release (D-ER) is indicated to improve walking in people with multiple sclerosis (MS) as demonstrated by an increase in walking speed. This study assessed the effects of D-ER on accelerometer-based measures in people with MS, including intensity of walking and total amount of walking during daily activities. METHODS: In this double-blind placebo-controlled crossover study, people with MS-related walking difficulty were randomized (1:1) to receive 4 weeks of D-ER 10 mg twice daily and 4 weeks of placebo in either order separated by a 2-week washout. Participants wore accelerometers for 7 days at baseline and week 3 of each on-drug period. The primary outcome was the peak activity index (PAI), defined as the most intense 30 individual minutes of the day (strides per minute). Secondary outcomes included daily step count, 6-Minute Walk Test (6MWT), Timed Up and Go (TUG) test, and patient-reported outcomes. A mixed-effects repeated-measures statistical model was used. RESULTS: Forty-three participants were randomized (mean Expanded Disability Status Scale score, 5.17). Least squares mean (standard error) change from baseline on the PAI was 0.6 (0.54) strides/min on D-ER and 0.3 (0.55) strides/min on placebo and in daily step count was 148.7 (222.4) on D-ER and 128.0 (225.4) on placebo. Other accelerometer-based measures and the 6MWT showed no significant differences between D-ER and placebo. The TUG test (P = .042) favored D-ER. There were no serious adverse events. CONCLUSIONS: Dalfampridine did not show an effect on accelerometer-measured ambulatory activity in people with MS-related walking difficulty. More work is needed to confirm these results. PMID- 27551239 TI - Drug induced exfoliative dermatitis: state of the art. AB - Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Overall, T cells are the central player of these immune-mediated drug reactions. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED. PMID- 27551242 TI - NAPS-MS: Natalizumab Effects on Parameters of Sleep in Patients with Multiple Sclerosis. AB - BACKGROUND: Patients with multiple sclerosis (MS) have higher rates of fatigue, mood disturbance, and cognitive impairments than healthy populations. Disease modifying agents may affect sleep. Although patients taking natalizumab often show improvement in fatigue during the first year of therapy, the mechanism behind this effect is unknown. The aim of the NAPS-MS study was to investigate whether natalizumab affected objective measures of sleep as determined by polysomnography (PSG) and multiple sleep latency testing (MSLT) in patients with MS with fatigue or sleepiness initiating therapy. Additional goals were to evaluate changes in measures of fatigue, mood, and cognition and to correlate these measures with objective sleep measures. METHODS: Patients underwent PSG and MSLT before their first natalizumab infusion and after their seventh. Patients completed the Modified Fatigue Impact Scale, Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and visual analogue scale for fatigue (VAS-F) at their first, fourth, and seventh natalizumab infusions. NeuroTrax cognitive tests and the Hospital Anxiety and Depression Scale (HADS) were performed at the first and seventh natalizumab infusions. RESULTS: Changes in sleep efficiency, wakefulness after sleep onset, and multiple sleep latency from baseline to 6 months of therapy did not reach significance. The FSS, VAS-F, ESS, and HADS scores were significantly improved after 6 months of therapy; cognitive scores were not significantly improved. CONCLUSIONS: Although treatment with natalizumab was associated with improvements in fatigue, sleepiness, and mood, changes in objective measures of sleep were not significant. PMID- 27551243 TI - The Perceived Deficits Questionnaire: Perception, Deficit, or Distress? AB - BACKGROUND: Cognitive dysfunction affects approximately 43% to 70% of individuals with multiple sclerosis (MS) and is an important determinant of several functional outcomes in MS and quality of life. Brief neuropsychological test batteries have been developed specifically for use in MS and are widely used to aid clinicians in assessing levels of cognitive impairment in MS. Neuropsychologists and neurologists also frequently use briefer screening measures, such as the Perceived Deficits Questionnaire (PDQ), to assist in determining whether a more extensive neuropsychological evaluation is warranted. However, despite the ease of such measures, the relationship between self-report and objective cognitive impairment has been inconsistent, at best. Moreover, factors such as depression, fatigue, anxiety, and personality have been found to be more related to reports of cognitive difficulties. The purpose of the present study was to clarify the relationship between subjective cognitive concerns and objective cognitive impairment while accounting for related symptoms. METHODS: We examined the association of self-reported cognitive concerns on the PDQ with objective cognitive measures, as well as depression, anxiety, fatigue, and self efficacy. RESULTS: There was no relationship between self-reported cognitive concerns and objective performance. Rather, reports on the PDQ were more correlated with reports of depression, anxiety, fatigue, and self-efficacy. CONCLUSIONS: Depression and poor self-efficacy can contribute to reports of cognitive difficulties. Effective treatment to improve these factors seems warranted given the impact of perceived cognitive impairment on outcomes in MS and the potential for more accurate self-reports. PMID- 27551244 TI - Coping with Multiple Sclerosis Scale: Reconsideration of the Factorial Structure. AB - BACKGROUND: The Coping with Multiple Sclerosis Scale (CMSS) was developed to assess coping strategies specific to multiple sclerosis (MS). Despite its wide application in MS research, psychometric support for the CMSS remains limited to the initial factor analytic investigation by Pakenham in 2001. METHODS: The current investigation assessed the factor structure and construct validity of the CMSS. Participants with MS (N = 453) completed the CMSS, as well as measures of disability related to MS (Multiple Sclerosis Impact Scale), quality of life (World Health Organization Quality of Life Brief Scale), and anxiety and depression (Hospital Anxiety and Depression Scale). RESULTS: The original factor structure reported by Pakenham was a poor fit to the data. An alternate seven factor structure was identified using exploratory factor analysis. Although there were some similarities with the existing CMSS subscales, differences in factor content and item loadings were found. Relationships between the revised CMSS subscales and additional measures were assessed, and the findings were consistent with previous research. CONCLUSIONS: Refinement of the CMSS is suggested, especially for subscales related to acceptance and avoidance strategies. Until further research is conducted on the revised CMSS, it is recommended that the original CMSS continue to be administered. Clinicians and researchers should be mindful of lack of support for the acceptance and avoidance subscales and should seek additional scales to assess these areas. PMID- 27551245 TI - Assessing Four Quality Indicators for Multiple Sclerosis Management Through Patient-Reported Data. AB - BACKGROUND: Although hundreds of quality indicators (QIs) have been developed for various chronic conditions, QIs specific to multiple sclerosis (MS) care have only recently been developed. We sought to examine the extent to which the self reported care of individuals with MS meets four recently developed MS QIs related to treatment of depression, spasticity, and fatigue and timely initiation of disease-modifying agents (DMAs) for relapsing MS. METHODS: Using the Sonya Slifka Study data, we examined the proportion of the MS population meeting four QIs (based on patient-reported data) in a sample of individuals with MS in 2007-2009. For the three diagnoses, meeting the QI was defined as receiving appropriate medication or seeing a provider for treatment of the diagnosis; for timely initiation, it was defined as receiving a DMA within 3 months of a relapsing MS diagnosis. We also examined differences in characteristics between respondents who met the QI versus those who did not. RESULTS: Approximately two-thirds of people with MS in this sample, per the predefined criteria, met the QIs for treatment of depression, management of spasticity, and DMA initiation within 3 months of a relapsing diagnosis, and approximately one-fifth met the QI for management of fatigue. There were some significant differences in characteristics between respondents who met the QIs and those who did not. CONCLUSIONS: This study examined a subset of MS QIs based on patient-reported data. Additional data sources are needed to fully assess compliance with MS QIs. PMID- 27551246 TI - Management Strategies for Flu-Like Symptoms and Injection-Site Reactions Associated with Peginterferon Beta-1a: Obtaining Recommendations Using the Delphi Technique. AB - BACKGROUND: Flu-like symptoms (FLSs) and injection-site reactions (ISRs) have been reported with interferon beta treatments for multiple sclerosis (MS). We sought to obtain consensus on the characteristics/management of FLSs/ISRs in patients with relapsing-remitting MS based on experiences from the randomized, placebo-controlled ADVANCE study of peginterferon beta-1a. METHODS: ADVANCE investigators with a predefined number of enrolled patients were eligible to participate in a consensus-generating exercise using a modified Delphi method. An independent steering committee oversaw the development of two sequential Delphi questionnaires. An average rating (AR) of 2.7 or more was defined as consensus a priori. RESULTS: Thirty and 29 investigators (ie, responders) completed questionnaires 1 and 2, respectively, representing 374 patients from ADVANCE. Responders reported that the incidence/duration of FLSs/ISRs in their typical patient generally declined after 3 months of treatment. Responders reached consensus that FLSs typically last up to 24 hours (AR = 3.17) and have mild/moderate effects on activities of daily living (AR = 3.34). Patients should initiate acetaminophen/nonsteroidal anti-inflammatory drug treatment on a scheduled basis (AR = 3.31) and change the timing of injection (AR = 3.28) to manage FLSs. Injection-site rotation/cooling and drug administration at room temperature (all AR >= 3.10) were recommended for managing ISRs. Patient education on FLSs/ISRs was advocated before treatment initiation. CONCLUSIONS: Delphi responders agreed on the management strategies for FLSs/ISRs and agreed that patient education is critical to set treatment expectations and promote adherence. PMID- 27551248 TI - Letter From The Editor. PMID- 27551247 TI - Editorial. PMID- 27551249 TI - Current Diagnosis and Management of Suspected Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy. AB - Suspected reflux symptoms that are refractory to proton pump inhibitors (PPIs) are rapidly becoming the most common presentation of gastroesophageal reflux disease (GERD) in patients seen in gastroenterology clinics. These patients are a heterogeneous group, differing in symptom frequency and severity, PPI dosing regimens, and responses to therapy (from partial to absent). Before testing, the physician needs to question the patient carefully about PPI compliance and the timing of drug intake in relation to meals. Switching PPIs or doubling the dose is the next step, but only 20% to 25% of the group refractory to PPIs will respond. The first diagnostic test should be upper gastrointestinal endoscopy. In more than 90% of cases, the results will be normal, but persistent esophagitis may suggest pill esophagitis, eosinophilic esophagitis, or rarer diseases, such as lichen planus, Zollinger-Ellison syndrome, or genotype variants of PPI metabolism. If the endoscopy results are normal, esophageal manometry and especially reflux testing should follow. Whether patients should be tested on or off PPI therapy is controversial. Most physicians prefer to test patients off PPIs to identify whether abnormal acid reflux is even present; if it is not, PPIs can be stopped and other diagnoses sought. Testing patients on PPI therapy allows nonacid reflux to be identified, but more than 50% of patients have a normal test result, leaving the clinician with a conundrum-whether to stop PPIs or continue them because the GERD is being treated adequately. Alternative diagnoses in patients with refractory GERD and normal reflux testing include achalasia, eosinophilic esophagitis, gastroparesis, rumination, and aerophagia. However, more than 50% will be given the diagnosis of functional heartburn, a visceral hypersensitivity syndrome. Treating patients with PPI-refractory GERD-like symptoms can be difficult and frustrating. Any of the following may help: a histamine-2 receptor antagonist at night, baclofen to decrease transient lower esophageal sphincter relaxations, pain modulators, acupuncture, or hypnotherapy. At this time, antireflux surgery should be limited to patients with abnormal acid reflux defined by pH testing and a good correlation of symptoms with acid reflux. PMID- 27551251 TI - Noninvasive Markers of Disease Activity in Inflammatory Bowel Disease. AB - It is often difficult to assess disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers are a means of quantifying often nebulous symptoms without subjecting patients to endoscopy or radiation. This paper highlights markers present in feces, serum, or urine that have all been compared with the gold standard, histologic analysis of endoscopically collected specimens. Two categories of markers are featured: well-researched markers of mucosal inflammation with high sensitivity and specificity (calprotectin, lactoferrin, and S100A12) and novel promising markers, some of which are already clinically employed for reasons unrelated to IBD (interleukin [IL]-17, IL-33/ST2, adenosine deaminase, polymorphonuclear elastase, matrix metalloproteinase-9, neopterin, serum M30, and fecal immunohistochemistry). The data pertaining to the more established markers are intended to highlight recent clinical applications for these markers (ie, assessing disease outside of the colon or in the pediatric population as well as being a cost-saving alternative to colonoscopy to screen for IBD). As there is no evidence to date that a specific marker will accurately be able to represent the entire IBD patient population, it is likely that a combination of the existing markers will be most clinically relevant to the practicing gastroenterologist attempting to evaluate disease severity in a specific patient. Familiarity with the most promising emerging markers will allow a better understanding of new studies and their impact on patient care. PMID- 27551253 TI - Recent Advances in Endoscopy Sedation: The Anesthesiologist's Perspective. PMID- 27551252 TI - Management of the Acid Pocket. PMID- 27551254 TI - Hepatocyte Transplantation. PMID- 27551250 TI - Management Strategies for Abdominal Bloating and Distension. AB - Bloating and distension are among the most common gastrointestinal complaints reported by patients with functional gut disorders and by the general population. These 2 complaints are also among the most prevalent of the severe symptoms reported by patients with irritable bowel syndrome. Nonetheless, only a limited number of published studies have specifically addressed bloating; it is infrequently studied as a primary endpoint, and what little systematic information exists has often been garnered from the assessment of secondary endpoints or the dissection of composite endpoints. This lack of data, and our consequent limited understanding of the pathophysiology of bloating, had hampered the quest for effective and targeted therapies until recently. Advances in the knowledge of underlying mechanisms, particularly with regard to the roles of diet, poorly absorbed fermentable carbohydrates, dysbiosis of the gut bacteria, alterations in visceral hypersensitivity, and abnormal viscerosomatic reflexes, have enabled the development of improved treatment options. The most significant recent advance has been a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which significantly reduces patients' symptoms and improves quality of life. Given the prevalence of bloating and its perceived severity, it is clear that further studies regarding the pathogenesis and treatment of this problem are needed. PMID- 27551255 TI - Neurologic Manifestations of Inflammatory Bowel Disease. PMID- 27551256 TI - Update on Anti-Angiogenesis Therapy in Colorectal Cancer. AB - Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti angiogenic agents and others are as yet unanswered. PMID- 27551258 TI - ERP Correlates of Simulated Purchase Decisions. AB - Decision making in economic context is an everyday activity but its neuronal correlates are poorly understood. The present study aimed at investigating the electrophysiological brain activity during simulated purchase decisions of technical products for a lower or higher price relative to a mean price estimated in a pilot study. Expectedly, participants mostly decided to buy a product when it was cheap and not to buy when it was expensive. However, in some trials they made counter-conformity decisions to buy a product for a higher than the average price or not to buy it despite an attractive price. These responses took more time and the variability of the response latency was enhanced relative to conformity responses. ERPs showed enhanced conflict related fronto-central N2 during both types of counter-conformity compared to conformity decisions. A reverse pattern was found for the P3a and P3b. The response-locked P3 (r-P3) was larger and the subsequent CNV smaller for counter-conformity than conformity decisions. We assume that counter-conformity decisions elevate the response threshold (larger N2), intensify response evaluation (r-P3) and attenuate the preparation for the next trial (CNV). These effects were discussed in the framework of the functional role of the fronto-parietal cortex in economic decision making. PMID- 27551257 TI - Multifaceted Role of Sialylation in Prion Diseases. AB - Mammalian prion or PrP(Sc) is a proteinaceous infectious agent that consists of a misfolded, self-replicating state of a sialoglycoprotein called the prion protein, or PrP(C). Sialylation of the prion protein N-linked glycans was discovered more than 30 years ago, yet the role of sialylation in prion pathogenesis remains poorly understood. Recent years have witnessed extraordinary growth in interest in sialylation and established a critical role for sialic acids in host invasion and host-pathogen interactions. This review article summarizes current knowledge on the role of sialylation of the prion protein in prion diseases. First, we discuss the correlation between sialylation of PrP(Sc) glycans and prion infectivity and describe the factors that control sialylation of PrP(Sc). Second, we explain how glycan sialylation contributes to the prion replication barrier, defines strain-specific glycoform ratios, and imposes constraints for PrP(Sc) structure. Third, several topics, including a possible role for sialylation in animal-to-human prion transmission, prion lymphotropism, toxicity, strain interference, and normal function of PrP(C), are critically reviewed. Finally, a metabolic hypothesis on the role of sialylation in the etiology of sporadic prion diseases is proposed. PMID- 27551260 TI - Astrocyte Reactivity Following Blast Exposure Involves Aberrant Histone Acetylation. AB - Blast induced neurotrauma (BINT) is a prevalent injury within military and civilian populations. The injury is characterized by persistent inflammation at the cellular level which manifests as a multitude of cognitive and functional impairments. Epigenetic regulation of transcription offers an important control mechanism for gene expression and cellular function which may underlie chronic inflammation and result in neurodegeneration. We hypothesize that altered histone acetylation patterns may be involved in blast induced inflammation and the chronic activation of glial cells. This study aimed to elucidate changes to histone acetylation occurring following injury and the roles these changes may have within the pathology. Sprague Dawley rats were subjected to either a 10 or 17 psi blast overpressure within an Advanced Blast Simulator (ABS). Sham animals underwent the same procedures without blast exposure. Memory impairments were measured using the Novel Object Recognition (NOR) test at 2 and 7 days post injury. Tissues were collected at 7 days for Western blot and immunohistochemistry (IHC) analysis. Sham animals showed intact memory at each time point. The novel object discrimination decreased significantly between two and 7 days for each injury group (p < 0.05). This is indicative of the onset of memory impairment. Western blot analysis showed glial fibrillary acidic protein (GFAP), a known marker of activated astrocytes, was elevated in the prefrontal cortex (PFC) following blast exposure for both injury groups. Analysis of histone protein extract showed no changes in the level of any total histone proteins within the PFC. However, acetylation levels of histone H2b, H3, and H4 were decreased in both groups (p < 0.05). Co-localization immunofluorescence was used to further investigate any potential correlation between decreased histone acetylation and astrocyte activation. These experiments showed a similar decrease in H3 acetylation in astrocytes exposed to a 17 psi blast but not a 10 psi blast. Further investigation of gene expression by polymerase chain reaction (PCR) array, showed dysregulation of several cytokine and cytokine receptors that are involved in neuroinflammatory processes. We have shown aberrant histone acetylation patterns involved in blast induced astrogliosis and cognitive impairments. Further understanding of their role in the injury progression may lead to novel therapeutic targets. PMID- 27551259 TI - Ammonia as a Potential Neurotoxic Factor in Alzheimer's Disease. AB - Ammonia is known to be a potent neurotoxin that causes severe negative effects on the central nervous system. Excessive ammonia levels have been detected in the brain of patients with neurological disorders such as Alzheimer disease (AD). Therefore, ammonia could be a factor contributing to the progression of AD. In this review, we provide an introduction to the toxicity of ammonia and putative ammonia transport proteins. We also hypothesize how ammonia may be linked to AD. Additionally, we discuss the evidence that support the hypothesis that ammonia is a key factor contributing to AD progression. Lastly, we summarize the old and new experimental evidence that focuses on energy metabolism, mitochondrial function, inflammatory responses, excitatory glutamatergic, and GABAergic neurotransmission, and memory in support of our ammonia-related hypotheses of AD. PMID- 27551261 TI - Glia: A Neglected Player in Non-invasive Direct Current Brain Stimulation. AB - Non-invasive electrical brain stimulation by application of direct current (DCS) promotes plasticity in neuronal networks in vitro and in in vivo. This effect has been mainly attributed to the direct modulation of neurons. Glia represents approximately 50% of cells in the brain. Glial cells are electrically active and participate in synaptic plasticity. Despite of that, effects of DCS on glial structures and on interaction with neurons are only sparsely investigated. In this perspectives article we review the current literature, present own dose response data and provide a framework for future research from two points of view: first, the direct effects of DCS on glia and second, the contribution of glia to DCS related neuronal plasticity. PMID- 27551262 TI - What Is the Effect of Basic Emotions on Directed Forgetting? Investigating the Role of Basic Emotions in Memory. AB - Studies presenting memory-facilitating effect of emotions typically focused on affective dimensions of arousal and valence. Little is known, however, about the extent to which stimulus-driven basic emotions could have distinct effects on memory. In the present paper we sought to examine the modulatory effect of disgust, fear, and sadness on intentional remembering and forgetting using widely used item-method directed forgetting (DF) paradigm. Eighteen women underwent fMRI scanning during encoding phase in which they were asked either to remember (R) or to forget (F) pictures. In the test phase all previously used stimuli were re presented together with the same number of new pictures and participants had to categorize them as old or new, irrespective of the F/R instruction. On the behavioral level we found a typical DF effect, i.e., higher recognition rates for to-be-remembered (TBR) items than to-be-forgotten (TBF) ones for both neutral and emotional categories. Emotional stimuli had higher recognition rate than neutral ones, while among emotional those eliciting disgust produced highest recognition, but at the same time induced more false alarms. Therefore, when false alarm corrected recognition was examined the DF effect was equally strong irrespective of emotion. Additionally, even though subjects rated disgusting pictures as more arousing and negative than other picture categories, logistic regression on the item level showed that the effect of disgust on recognition memory was stronger than the effect of arousal or valence. On the neural level, ROI analyses (with valence and arousal covariates) revealed that correctly recognized disgusting stimuli evoked the highest activity in the left amygdala compared to all other categories. This structure was also more activated for remembered vs. forgotten stimuli, but only in case of disgust or fear eliciting pictures. Our findings, despite several limitations, suggest that disgust have a special salience in memory relative to other negative emotions, which cannot be put down to differences in arousal or valence. The current results thereby support the suggestion that a purely dimensional model of emotional influences on cognition might not be adequate to account for observed effects. PMID- 27551263 TI - Improving Dorsal Stream Function in Dyslexics by Training Figure/Ground Motion Discrimination Improves Attention, Reading Fluency, and Working Memory. AB - There is an ongoing debate about whether the cause of dyslexia is based on linguistic, auditory, or visual timing deficits. To investigate this issue three interventions were compared in 58 dyslexics in second grade (7 years on average), two targeting the temporal dynamics (timing) of either the auditory or visual pathways with a third reading intervention (control group) targeting linguistic word building. Visual pathway training in dyslexics to improve direction discrimination of moving test patterns relative to a stationary background (figure/ground discrimination) significantly improved attention, reading fluency, both speed and comprehension, phonological processing, and both auditory and visual working memory relative to controls, whereas auditory training to improve phonological processing did not improve these academic skills significantly more than found for controls. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways is a fundamental cause of dyslexia, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological deficits. This study demonstrates that visual movement direction-discrimination can be used to not only detect dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning. PMID- 27551264 TI - Reconsidering Animal Models of Major Depressive Disorder in the Elderly. PMID- 27551265 TI - Transitioning Pharmacogenomics into the Clinical Setting: Training Future Pharmacists. AB - Pharmacogenomics, once hailed as a futuristic approach to pharmacotherapy, has transitioned to clinical implementation. Although logistic and economic limitations to clinical pharmacogenomics are being superseded by external measures such as preemptive genotyping, implementation by clinicians has met resistance, partly due to a lack of education. Pharmacists, with extensive training in pharmacology and pharmacotherapy and accessibility to patients, are ideally suited to champion clinical pharmacogenomics. This study aimed to analyze the outcomes of an innovative pharmacogenomic teaching approach. Second-year student pharmacists enrolled in a required, 15-week pharmaceutical care lab course in 2015 completed educational activities including lectures and small group work focusing on practical pharmacogenomics. Reflecting the current landscape of direct-to-consumer (DTC) genomic testing, students were offered 23andMe genotyping. Students completed surveys regarding their attitudes and confidence on pharmacogenomics prior to and following the educational intervention. Paired pre- and post-intervention responses were analyzed with McNemar's test for binary comparisons and the Wilcoxon signed-rank test for Likert items. Responses between genotyped and non-genotyped students were analyzed with Fisher's exact test for binary comparisons and the Mann-Whitney U test for Likert items. Responses were analyzed for all student pharmacists who voluntarily completed the pre-intervention survey (N = 121, 83% response) and for student pharmacists who completed both pre- and post-intervention surveys (N = 39, 27% response). Of those who completed both pre- and post-intervention surveys, 59% obtained genotyping. Student pharmacists demonstrated a significant increase in their knowledge of pharmacogenomic resources (17.9 vs. 56.4%, p < 0.0001) and confidence in applying pharmacogenomic information to manage patients' drug therapy (28.2 vs. 48.7%, p = 0.01), particularly if the student had received genotyping. Student pharmacists understanding of the risks and benefits of using personal genome testing services significantly increased (55.3 vs. 86.8%, p = 0.001) along with agreement that personal genomics would likely play an important role in their future career (47.4 vs. 76.3%, p = 0.01), particularly among students who participated in genotyping. The educational intervention, including personal genotyping, was feasible, and positively enhanced students' reflections, and attitudes toward pharmacogenomics in a professional pharmacy program. PMID- 27551266 TI - Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol. AB - Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis. PMID- 27551268 TI - Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study. AB - BACKGROUND: Chronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modulate cortico-limbic activity resulting in reduction of drug craving. AIMS: In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). METHODS: Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve repetitive TMS (rTMS) sessions were administered three times a week for 4 weeks at 100% of motor threshold, over bilateral PFC. Cocaine intake (ng/mg) was assessed by hair analysis at baseline (before treatment, T0), after 1 month (end of treatment, T1), 3 (T2), and 6 (T3) months later. All subjects received psychological support weekly. RESULTS: The two-way ANOVA for repeated measures did not show a significant effect of the interaction between time and treatment (F 4,32 = 0.35; p = 0.87). Despite that result indicated no difference in the effect of the two conditions (active vs. sham) along time, a decreasing trend in cocaine consumption in active TMS group (F 3,23 = 3.42; p = 0.04) vs. sham (F 3,15 = 1.88; p = 0.20) was observed when we performed exploratory analysis with time as factor. Indeed, Post hoc comparisons showed a significant reduction in the amount of cocaine detected from the onset to 3 months later (T0-T2; p = 0.02) and to the end of treatment (T0-T3; p = 0.01) in addicts from the active group. CONCLUSION: Bilateral rTMS of PFC at 10 Hz did not show a significant effect on cocaine intake compared to sham. However, a long-term reduction on cocaine intake in active TMS-treated patients was observed when we considered the time as factor. Further studies are required to confirm these encouraging but preliminary findings, in order to consolidate rTMS as a valid tool to treat cocaine addiction. PMID- 27551270 TI - Structural Validity of the Pittsburgh Sleep Quality Index in Chinese Undergraduate Students. AB - The purpose of this study was to examine the structural validity of the Pittsburgh Sleep Quality Index (PSQI) in Chinese undergraduate students. A cross sectional questionnaire survey with 631 Chinese undergraduate students was conducted, and the questionnaire package included a measure of demographic characteristics, PSQI, Chinese editions of Center for Epidemiologic Studies Depression, State- Trait Anxiety Inventory, Rumination Response Scale, and Perceived Social Support Scale. Results showed that the item "use of sleep medicine" was not suitable for use with this population, that a two-factor model provided the best fit to the data as assessed through confirmatory factor analysis, and that other indices were consistently correlated with the sleep quality but not the sleep efficiency factor. PMID- 27551271 TI - Strengthening Children's Advertising Defenses: The Effects of Forewarning of Commercial and Manipulative Intent. AB - This study investigated whether a forewarning of advertising's intent can increase children's (N = 159, 8-10 years old) defenses against television commercials to lower their desire for advertised products. Two different forewarnings were tested, one for advertising's commercial intent or warning for the promotional nature, and one for advertising's manipulative intent or warning for the deceptive nature. Results showed that only the warning of manipulative intent prior to advertising exposure was successful in increasing children's advertising defenses. This forewarning activated children's attitudinal advertising literacy (i.e., skepticism toward the commercial), which in turn led to lower advertised product desire. The forewarning of commercial intent was not effective in strengthening children's advertising defenses. These findings have important implications for interventions that aim to lower children's desire for (unhealthy) advertised products by activating their advertising literacy. PMID- 27551267 TI - Insights into the Regulatory Role of Non-coding RNAs in Cancer Metabolism. AB - Cancer represents a complex disease originated from alterations in several genes leading to disturbances in important signaling pathways in tumor biology, favoring heterogeneity that promotes adaptability and pharmacological resistance of tumor cells. Metabolic reprogramming has emerged as an important hallmark of cancer characterized by the presence of aerobic glycolysis, increased glutaminolysis and fatty acid biosynthesis, as well as an altered mitochondrial energy production. The metabolic switches that support energetic requirements of cancer cells are closely related to either activation of oncogenes or down modulation of tumor-suppressor genes, finally leading to dysregulation of cell proliferation, metastasis and drug resistance signals. Non-coding RNAs (ncRNAs) have emerged as one important kind of molecules that can regulate altered genes contributing, to the establishment of metabolic reprogramming. Moreover, diverse metabolic signals can regulate ncRNA expression and activity at genetic, transcriptional, or epigenetic levels. The regulatory landscape of ncRNAs may provide a new approach for understanding and treatment of different types of malignancies. In this review we discuss the regulatory role exerted by ncRNAs on metabolic enzymes and pathways involved in glucose, lipid, and amino acid metabolism. We also review how metabolic stress conditions and tumoral microenvironment influence ncRNA expression and activity. Furthermore, we comment on the therapeutic potential of metabolism-related ncRNAs in cancer. PMID- 27551269 TI - The Associations of Dyadic Coping and Relationship Satisfaction Vary between and within Nations: A 35-Nation Study. AB - OBJECTIVE: Theories about how couples help each other to cope with stress, such as the systemic transactional model of dyadic coping, suggest that the cultural context in which couples live influences how their coping behavior affects their relationship satisfaction. In contrast to the theoretical assumptions, a recent meta-analysis provides evidence that neither culture, nor gender, influences the association between dyadic coping and relationship satisfaction, at least based on their samples of couples living in North America and West Europe. Thus, it is an open questions whether the theoretical assumptions of cultural influences are false or whether cultural influences on couple behavior just occur in cultures outside of the Western world. METHOD: In order to examine the cultural influence, using a sample of married individuals (N = 7973) from 35 nations, we used multilevel modeling to test whether the positive association between dyadic coping and relationship satisfaction varies across nations and whether gender might moderate the association. RESULTS: RESULTS reveal that the association between dyadic coping and relationship satisfaction varies between nations. In addition, results show that in some nations the association is higher for men and in other nations it is higher for women. CONCLUSIONS: Cultural and gender differences across the globe influence how couples' coping behavior affects relationship outcomes. This crucial finding indicates that couple relationship education programs and interventions need to be culturally adapted, as skill trainings such as dyadic coping lead to differential effects on relationship satisfaction based on the culture in which couples live. PMID- 27551272 TI - Naive Learners Show Cross-Domain Transfer after Distributional Learning: The Case of Lexical and Musical Pitch. AB - Experienced listeners of a particular acoustic cue in either speech or music appear to have an advantage when perceiving a similar cue in the other domain (i.e., they exhibit cross-domain transfer). One explanation for cross-domain transfer relates to the acquisition of the foundations of speech and music: if acquiring pitch-based elements in speech or music results in heightened attention to pitch in general, then cross-domain transfer of pitch may be observed, which may explain the cross-domain phenomenon seen among listeners of a tone language and listeners with musical training. Here, we investigate this possibility in naive adult learners, who were trained to acquire pitch-based elements using a distributional learning paradigm, to provide a proof-of-concept for the explanation. Learners were exposed to a stimulus distribution spanning either a Thai lexical tone minimal pair or a novel musical chord minimal pair. Within each domain, the distribution highlights pitch to facilitate learning of two different sounds (Bimodal distribution) or the distribution minimizes pitch so that the input is inferred to be from a single sound (Unimodal distribution). Learning was assessed before and after exposure to the distribution using discrimination tasks with both Thai tone and musical chord minimal pairs. We hypothesize: (i) distributional learning for learners in both the tone and the chord distributions, that is, pre-to-post improvement in discrimination after exposure to the Bimodal but not the Unimodal distribution; and (ii) for both the tone and chord conditions, learners in the Bimodal conditions but not those in the Unimodal conditions will show cross-domain transfer, as indexed by improvement in discrimination of test items in the domain other than what they were trained on. The results support both hypotheses, suggesting that distributional learning is not only used to acquire the foundations of speech and music, but may also play a role in cross-domain transfer: as a result of learning primitives based on a particular cue, learners show heightened attention to that cue in any auditory signal. PMID- 27551273 TI - Near-Infrared Spectroscopy - Electroencephalography-Based Brain-State-Dependent Electrotherapy: A Computational Approach Based on Excitation-Inhibition Balance Hypothesis. AB - Stroke is the leading cause of severe chronic disability and the second cause of death worldwide with 15 million new cases and 50 million stroke survivors. The poststroke chronic disability may be ameliorated with early neuro rehabilitation where non-invasive brain stimulation (NIBS) techniques can be used as an adjuvant treatment to hasten the effects. However, the heterogeneity in the lesioned brain will require individualized NIBS intervention where innovative neuroimaging technologies of portable electroencephalography (EEG) and functional-near infrared spectroscopy (fNIRS) can be leveraged for Brain State Dependent Electrotherapy (BSDE). In this hypothesis and theory article, we propose a computational approach based on excitation-inhibition (E-I) balance hypothesis to objectively quantify the poststroke individual brain state using online fNIRS-EEG joint imaging. One of the key events that occurs following Stroke is the imbalance in local E-I (that is the ratio of Glutamate/GABA), which may be targeted with NIBS using a computational pipeline that includes individual "forward models" to predict current flow patterns through the lesioned brain or brain target region. The current flow will polarize the neurons, which can be captured with E-I-based brain models. Furthermore, E-I balance hypothesis can be used to find the consequences of cellular polarization on neuronal information processing, which can then be implicated in changes in function. We first review the evidence that shows how this local imbalance between E-I leading to functional dysfunction can be restored in targeted sites with NIBS (motor cortex and somatosensory cortex) resulting in large-scale plastic reorganization over the cortex, and probably facilitating recovery of functions. Second, we show evidence how BSDE based on E-I balance hypothesis may target a specific brain site or network as an adjuvant treatment. Hence, computational neural mass model based integration of neurostimulation with online neuroimaging systems may provide less ambiguous, robust optimization of NIBS, and its application in neurological conditions and disorders across individual patients. PMID- 27551274 TI - The Diagnostic Accuracy of Truncal Ataxia and HINTS as Cardinal Signs for Acute Vestibular Syndrome. AB - The head impulse, nystagmus type, test of skew (HINTS) protocol set a new paradigm to differentiate peripheral vestibular disease from stroke in patients with acute vestibular syndrome (AVS). The relationship between degree of truncal ataxia and stroke has not been systematically studied in patients with AVS. We studied a group of 114 patients who were admitted to a General Hospital due to AVS, 72 of them with vestibular neuritis (based on positive head impulse, abnormal caloric tests, and negative MRI) and the rest with stroke: 32 in the posterior inferior cerebellar artery (PICA) territory (positive HINTS findings, positive MRI) and 10 in the anterior inferior cerebellar artery (AICA) territory (variable findings and grade 3 ataxia, positive MRI). Truncal ataxia was measured by independent observers as grade 1, mild to moderate imbalance with walking independently; grade 2, severe imbalance with standing, but cannot walk without support; and grade 3, falling at upright posture. When we applied the HINTS protocol to our sample, we obtained 100% sensitivity and 94.4% specificity, similar to previously published findings. Only those patients with stroke presented with grade 3 ataxia. Of those with grade 2 ataxia (n = 38), 11 had cerebellar stroke and 28 had vestibular neuritis, not related to the patient's age. Grade 2-3 ataxia was 92.9% sensitive and 61.1% specific to detect AICA/PICA stroke in patients with AVS, with 100% sensitivity to detect AICA stroke. In turn, two signs (nystagmus of central origin and grade 2-3 Ataxia) had 100% sensitivity and 61.1% specificity. Ataxia is less sensitive than HINTS but much easier to evaluate. PMID- 27551276 TI - Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling. AB - Intact melanocortin signaling via the G protein-coupled receptors (GPCRs), melanocortin receptor 4 (MC4R), and melanocortin receptor 3 (MC3R) is crucial for body weight maintenance. So far, no connection between melanocortin signaling and hypothalamic inflammation has been reported. Using a bimolecular fluorescence complementation library screen, we identified a new interaction partner for these receptors, ring finger protein 11 (RNF11). RNF11 participates in the constitution of the A20 complex that is involved in reduction of tumor necrosis factor alpha (TNFalpha)-induced NFkappaB signaling, an important pathway in hypothalamic inflammation. Mice treated with high-fat diet (HFD) for 3 days demonstrated a trend toward an increase in hypothalamic Rnf11 expression, as shown for other inflammatory markers under HFD. Furthermore, Gs-mediated signaling of MC3/4R was demonstrated to be strongly reduced to 20-40% by co-expression of RNF11 despite unchanged total receptor expression. Cell surface expression was not affected for MC3R but resulted in a significant reduction of MC4R to 61% by co-expression with RNF11. Mechanisms linking HFD, inflammation, and metabolism remain partially understood. In this study, a new axis between signaling of specific body weight regulating GPCRs and factors involved in hypothalamic inflammation is suggested. PMID- 27551277 TI - Carbapenem Resistance in Acinetobacter baumannii and Other Acinetobacter spp. Causing Neonatal Sepsis: Focus on NDM-1 and Its Linkage to ISAba125. AB - Carbapenem-resistant determinants and their surrounding genetic structure were studied in Acinetobacter spp. from neonatal sepsis cases collected over 7 years at a tertiary care hospital. Acinetobacter spp. (n = 68) were identified by ARDRA followed by susceptibility tests. Oxacillinases, metallo-beta-lactamases (MBLs), extended-spectrum beta-lactamases and AmpCs, were detected phenotypically and/or by PCR followed by DNA sequencing. Transconjugants possessing the bla NDM-1(New Delhi metallo-beta-lactamase) underwent further analysis for plasmids, integrons and associated genes. Genetic environment of the carbapenemases were studied by PCR mapping and DNA sequencing. Multivariate logistic regression was used to identify risk factors for sepsis caused by NDM-1-harboring organisms. A. baumannii (72%) was the predominant species followed by A. calcoaceticus (10%), A. lwoffii (6%), A. nosocomialis (3%), A. junni (3%), A. variabilis (3%), A. haemolyticus (2%), and 14TU (2%). Fifty six percent of the isolates were meropenem-resistant. Oxacillinases present were OXA-23-like, OXA-58-like and OXA 51-like, predominately in A. baumannii. NDM-1 was the dominant MBL (22%) across different Acinetobacter spp. Isolates harboring NDM-1 also possessed bla (VIM-2, PER-1, VEB-2, CTX-M-15), armA, aac(6')Ib, aac(6')Ib-cr genes. bla NDM-1was organized in a composite transposon between two copies of ISAba125 in the isolates irrespective of the species. Further, OXA-23-like gene and OXA-58-like genes were linked with ISAba1 and ISAba3 respectively. Isolates were clonally diverse. Integrons were variable in sequence but not associated with carbapenem resistance. Most commonly found genes in the 5' and 3'conserved segment were aminoglycoside resistance genes (aadB, aadA2, aac4'), non-enzymatic chloramphenicol resistance gene (cmlA1g) and ADP-ribosylation genes (arr2, arr3). Outborn neonates had a significantly higher incidence of sepsis due to NDM-1 harboring isolates than their inborn counterparts. This study demonstrates the significance of both A. baumannii and other species of Acinetobacter in cases of neonatal sepsis over an extended period. Oxacillinases and bla NDM-1 are the major contributors to carbapenem resistance. The dissemination of the bla NDM-1 is likely linked to Tn125 in diverse clones of the isolates. PMID- 27551275 TI - Amyloidosis in Retinal Neurodegenerative Diseases. AB - As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Abeta) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer's disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer's patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer's patients. In this review, we first briefly discuss the biogenesis of Abeta, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Abeta. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Abeta amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a "window" to the brain. PMID- 27551278 TI - The First Temporal and Spatial Assessment of Vibrio Diversity of the Surrounding Seawater of Coral Reefs in Ishigaki, Japan. AB - Coral reefs perform a major role in regulating marine biodiversity and serve as hotspot for highly dynamic and diverse microbiomes as holobionts. Corals around Ishigaki, however, are at risk due to tremendous stressors including elevation of seawater temperature, eutrophication and so on. However, no information is currently available on how Vibrio diversity fluctuates spatially and temporally due to environmental determinants in Ishigaki coral reef ecosystems. The aim of this study is to elucidate spatiotemporal Vibrio diversity dynamic at both community and population levels and to assess the environmental drivers correlated to Vibrio abundance and diversity. The Vibrio community identified based on pyrH gene phylogeny of 685 isolates from seawater directly connecting to Ishigaki coral holobionts consisted of 22 known and 12 potential novel Vibrionaceae species. The most prominent species were V. hyugaensis, V. owensii and V. harveyi followed by V. maritimus/V. variabillis, V. campbellii, V. coralliilyticus, and Photobacterium rosenbergii. The Vibrio community fluctuations, assessed by PCoA with UniFrac distance and clustering with Euclidiean distance were varied less not only by year but also by site. Interestingly, significant positive correlation was observed between rising seawater temperature and the abundance of V. campbellii (r = 0.62; P < 0.05) whereas the opposite was observed for V. owensii (r = -0.58; P < 0.05) and the C6 group of V. hyugaensis (r = -0.62; P < 0.05). AdaptML-based microhabitat differentiation revealed that V. harveyi, V. campbellii, P. rosenbergii, and V. coralliilyticus populations were less-ecologically distinctive whereas V. astriarenae and V. ishigakensis were ecologically diverse. This knowledge could be important clue for the future actions of coral conservation. PMID- 27551279 TI - Recent Advances on Multi-Parameter Flow Cytometry to Characterize Antimicrobial Treatments. AB - The investigation on antimicrobial mechanisms is a challenging and crucial issue in the fields of food or clinical microbiology, as it constitutes a prerequisite to the development of new antimicrobial processes or compounds, as well as to anticipate phenomenon of microbial resistance. Nowadays it is accepted that a cells population exposed to a stress can cause the appearance of different cell populations and in particular sub-lethally compromised cells which could be defined as viable but non-culturable (VBNC). Recent advances on flow cytometry (FCM) and especially on multi-parameter flow cytometry (MP-FCM) provide the opportunity to obtain high-speed information at real time on damage at single cell level. This review gathers MP-FCM methodologies based on individual and simultaneous staining of microbial cells employed to investigate their physiological state following different physical and chemical antimicrobial treatments. Special attention will be paid to recent studies exploiting the possibility to corroborate MP-FCM results with additional techniques (plate counting, microscopy, spectroscopy, molecular biology techniques, membrane modeling) in order to elucidate the antimicrobial mechanism of action of a given antimicrobial treatment or compound. The combination of MP-FCM methodologies with these additional methods is namely a promising and increasingly used approach to give further insight in differences in microbial sub-population evolutions in response to antimicrobial treatments. PMID- 27551281 TI - Autochthonous Bacterial Isolates Successfully Stimulate In vitro Peripheral Blood Leukocytes of the European Sea Bass (Dicentrarchus labrax). AB - Commercially available probiotics are routinely administered as feed supplements in aquaculture important species. Among them, the European sea bass (Dicentrarchus labrax) is the most widely reared fish in the Mediterranean, whose rearing systems are highly variable between countries, affecting at some level the sustainability of production. After random isolation of autochthonous gut bacteria of the sea bass, their identification and pathogenicity testing, we have selected three potentially probiotic isolates; Pseudoalteromonas sp., Alteromonas sp., and Enterovibrio coralii. Selected isolates were tested and their immunostimulative efficiency was compared with a commercially available Lactobacillus casei isolate, inferring inflammatory, apoptotic and anti-pathogen response of sea bass' peripheral blood leukocytes. Phagocytic activity, respiratory burst, and expression of lysozyme, Mx protein, caspase 3, TNF-alpha, IL-10 genes was measured 1, 3, 5, and 12 h post-stimulation by four bacterial isolates to evaluate early kinetics of the responses. Best immunostimulative properties were observed in Pseudoalteromonas-stimulated leukocytes, followed by Alteromonas sp. and L. casei, while Enterovibrio coralii failed to induce significant stimulation. Based on such in vitro assay intestinal autochthonous bacterial isolates showed to have better immunostimulative effect in sea bass compared to aquaculture-widely used L. casei, and further steps need to engage tank and field feeding trials to evaluate long-term prophylactic suitability of the chosen isolates. A panel of biomarkers that represent pro-/anti-inflammatory, pro-/anti-apoptotic, and anti-bacteria/viral responses of the fish should be taken into consideration when evaluating the usefulness of the potential probiotic in aquaculture. PMID- 27551280 TI - Bacterial Communities: Interactions to Scale. AB - In the environment, bacteria live in complex multispecies communities. These communities span in scale from small, multicellular aggregates to billions or trillions of cells within the gastrointestinal tract of animals. The dynamics of bacterial communities are determined by pairwise interactions that occur between different species in the community. Though interactions occur between a few cells at a time, the outcomes of these interchanges have ramifications that ripple through many orders of magnitude, and ultimately affect the macroscopic world including the health of host organisms. In this review we cover how bacterial competition influences the structures of bacterial communities. We also emphasize methods and insights garnered from culture-dependent pairwise interaction studies, metagenomic analyses, and modeling experiments. Finally, we argue that the integration of multiple approaches will be instrumental to future understanding of the underlying dynamics of bacterial communities. PMID- 27551282 TI - Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell Epitope That Mediates Effective Protective Responses in HLA-A2.1/K(b) Transgenic Mice. AB - Hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. Our previous study showed that the CD8(+) T-cell epitope aa129-aa137 (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by human leukocyte antigen (HLA)-A*02, induced specific CD8(+) T-cell responses that controlled HTNV infection in humans. However, the in vivo immunogenicity of peptide FA9 and the effect of FA9-specific CD8(+) T-cell immunity remain unclear. Here, based on a detailed structural analysis of the peptide FA9/HLA-A*0201 complex and functional investigations using HLA-A2.1/K(b) transgenic (Tg) mice, we found that the overall structure of the peptide FA9/HLA-A*0201 complex displayed a typical MHC class I fold with Val2 and Ala9 as primary anchor residues and Val3 and Leu7 as secondary anchor residues that allow peptide FA9 to bind tightly with an HLA-A*0201 molecule. Residues in the middle portion of peptide FA9 extruding out of the binding groove may be the sites that allow for recognition by T-cell receptors. Immunization with peptide FA9 in HLA-A2.1/K(b) Tg mice induced FA9-specific cytotoxic T-cell responses characterized by the induction of high expression levels of interferon-gamma, tumor necrosis factor alpha, granzyme B, and CD107a. In an HTNV challenge trial, significant reductions in the levels of both the antigens and the HTNV RNA loads were observed in the liver, spleen, and kidneys of Tg mice pre-vaccinated with peptide FA9. Thus, our findings highlight the ability of HTNV epitope-specific CD8(+) T-cell immunity to control HTNV and support the possibility that the HTNV-NP FA9 peptide, naturally processed in vivo in an HLA-A*02-restriction manner, may be a good candidate for the development HTNV peptide vaccines. PMID- 27551283 TI - Genotypically Identifying Wheat Mesophyll Conductance Regulation under Progressive Drought Stress. AB - Photosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm) may considerably affect both photosynthesis and water use efficiency (WUE) in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L.) genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure) and non-stomatal (diffusional and biochemical) limits of net CO2 assimilation rate (AN). In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs), respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax). On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm) seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought. PMID- 27551284 TI - Striga Biocontrol on a Toothpick: A Readily Deployable and Inexpensive Method for Smallholder Farmers. AB - Striga hermonthica (witchweed) is a parasitic weed that attacks and significantly reduces the yields of maize, sorghum, millet, and sugarcane throughout sub Saharan Africa. Low cost management methods such as hand weeding, short crop rotations, trap cropping, or conventional biocontrol have not been effective. Likewise, Striga-tolerant or herbicide-resistant maize cultivars are higher yielding, but are often beyond the economic means of sustenance farmers. The fungal pathogen, Fusarium oxysporum f.sp. strigae, has been the object of numerous studies to develop Striga biocontrol. Under experimental conditions this pathogen can reduce the incidence of Striga infestation but field use is not extensive, perhaps because it has not been sufficiently effective in restoring crop yield and reducing the soil Striga seed bank. Here we brought together Kenyan and US crop scientists with smallholder farmers to develop and validate an effective biocontrol strategy for management of Striga on smallholder farms. Key components of this research project were the following: (1) Development of a two step method of fungal delivery, including laboratory coating of primary inoculum on toothpicks, followed by on-farm production of secondary field inoculum in boiled rice enabling delivery of vigorous, fresh inoculum directly to the seedbed; (2) Training of smallholder farmers (85% women), to produce the biocontrol agent and incorporate it into their maize plantings in Striga-infested soils and collect agronomic data. The field tests expanded from 30 smallholder farmers to a two-season, 500-farmer plot trial including paired plus and minus biocontrol plots with fertilizer and hybrid seed in both plots and; (3) Concerted selection of variants of the pathogen identified for enhanced virulence, as has been demonstrated in other host parasite systems were employed here on Striga via pathogen excretion of the amino acids L-leucine and L-tyrosine that are toxic to Striga but innocuous to maize. This overall strategy resulted in an average of >50% increased maize yield in the March to June rains season and >40% in the September to December rains season. Integration of this enhanced plant pathogen to Striga management in maize can significantly increase the maize yield of smallholder farmers in Kenya. PMID- 27551285 TI - Analysis of Magnaporthe oryzae Genome Reveals a Fungal Effector, Which Is Able to Induce Resistance Response in Transgenic Rice Line Containing Resistance Gene, Pi54. AB - Rice blast caused by Magnaporthe oryzae is one of the most important diseases of rice. Pi54, a rice gene that imparts resistance to M. oryzae isolates prevalent in India, was already cloned but its avirulent counterpart in the pathogen was not known. After decoding the whole genome of an avirulent isolate of M. oryzae, we predicted 11440 protein coding genes and then identified four candidate effector proteins which are exclusively expressed in the infectious structure, appresoria. In silico protein modeling followed by interaction analysis between Pi54 protein model and selected four candidate effector proteins models revealed that Mo-01947_9 protein model encoded by a gene located at chromosome 4 of M. oryzae, interacted best at the Leucine Rich Repeat domain of Pi54 protein model. Yeast-two-hybrid analysis showed that Mo-01947_9 protein physically interacts with Pi54 protein. Nicotiana benthamiana leaf infiltration assay confirmed induction of hypersensitive response in the presence of Pi54 gene in a heterologous system. Genetic complementation test also proved that Mo-01947_9 protein induces avirulence response in the pathogen in presence of Pi54 gene. Here, we report identification and cloning of a new fungal effector gene which interacts with blast resistance gene Pi54 in rice. PMID- 27551286 TI - Kaolin Foliar Application Has a Stimulatory Effect on Phenylpropanoid and Flavonoid Pathways in Grape Berries. AB - Drought, elevated air temperature, and high evaporative demand are increasingly frequent during summer in grape growing areas like the Mediterranean basin, limiting grapevine productivity and berry quality. The foliar exogenous application of kaolin, a radiation-reflecting inert mineral, has proven effective in mitigating the negative impacts of these abiotic stresses in grapevine and other fruit crops, however, little is known about its influence on the composition of the grape berry and on key molecular mechanisms and metabolic pathways notably important for grape berry quality parameters. Here, we performed a thorough molecular and biochemical analysis to assess how foliar application of kaolin influences major secondary metabolism pathways associated with berry quality-traits, leading to biosynthesis of phenolics and anthocyanins, with a focus on the phenylpropanoid, flavonoid (both flavonol- and anthocyanin biosynthetic) and stilbenoid pathways. In grape berries from different ripening stages, targeted transcriptional analysis by qPCR revealed that several genes involved in these pathways-VvPAL1, VvC4H1, VvSTSs, VvCHS1, VvFLS1, VvDFR, and VvUFGT-were more expressed in response to the foliar kaolin treatment, particularly in the latter maturation phases. In agreement, enzymatic activities of phenylalanine ammonia lyase (PAL), flavonol synthase (FLS), and UDP glucose:flavonoid 3-O-glucosyltransferase (UFGT) were about two-fold higher in mature or fully mature berries from kaolin-treated plants, suggesting regulation also at a transcriptional level. The expression of the glutathione S-transferase VvGST4, and of the tonoplast anthocyanin transporters VvMATE1 and VvABCC1 were also all significantly increased at veraison and in mature berries, thus, when anthocyanins start to accumulate in the vacuole, in agreement with previously observed higher total concentrations of phenolics and anthocyanins in berries from kaolin-treated plants, especially at full maturity stage. Metabolomic analysis by reverse phase LC-QTOF-MS confirmed several kaolin-induced modifications including a significant increase in the quantities of several secondary metabolites including flavonoids and anthocyanins in the latter ripening stages, probably resulting from the general stimulation of the phenylpropanoid and flavonoid pathways. PMID- 27551287 TI - The Ectopic Expression of CaRop1 Modulates the Response of Tobacco Plants to Ralstonia solanacearum and Aphids. AB - In plants, Rho-related GTPases (Rops) are versatile molecular switches that regulate various biological processes, although their exact roles are not fully understood. Herein, we provide evidence that the ectopic expression of a Rop derived from Capsicum annuum, designated CaRop1, in tobacco plants modulates the response of these plants to Ralstonia solanacearum or aphid attack. The deduced amino acid sequence of CaRop1 harbors a conserved Rho domain and is highly homologous to Rops of other plant species. Transient expression of a CaRop1-GFP fusion protein in Nicotiana benthamiana leaf epidermal cells revealed localization of the GFP signal to the plasma membrane, cytoplasm, and nucleus. Overexpression (OE) of the wild-type CaRop1 or its dominant-negative mutant (DN CaRop1) conferred substantial resistance to R. solanacearum infection and aphid attack, and this effect was accompanied by enhanced transcriptional expression of the hypersensitive-reaction marker gene HSR201; the jasmonic acid (JA)-responsive PR1b and LOX1; the insect resistance-associated NtPI-I, NtPI-II, and NtTPI; the ethylene (ET) production-associated NtACS1; and NPK1, a mitogen-activated protein kinase kinase kinase (MAPKKK) that interferes with N-, Bs2-, and Rx-mediated disease resistance. In contrast, OE of the constitutively active mutant of CaRop1(CA-CaRop1) enhanced susceptibility of the transgenic tobacco plants to R. solanacearum infection and aphid attack and downregulated or sustained the expression of HSR201, PR1b, NPK1, NtACS1, NtPI-I, NtPI-II, and NtTPI. These results collectively suggest that CaRop1 acts as a signaling switch in the crosstalk between Solanaceaes's response to R. solanacearum infection and aphid attack possibly via JA/ET-mediated signaling machinery. PMID- 27551289 TI - Detection of Significant Groups in Hierarchical Clustering by Resampling. AB - Hierarchical clustering is a simple and reproducible technique to rearrange data of multiple variables and sample units and visualize possible groups in the data. Despite the name, hierarchical clustering does not provide clusters automatically, and "tree-cutting" procedures are often used to identify subgroups in the data by cutting the dendrogram that represents the similarities among groups used in the agglomerative procedure. We introduce a resampling-based technique that can be used to identify cut-points of a dendrogram with a significance level based on a reference distribution for the heights of the branch points. The evaluation on synthetic data shows that the technique is robust in a variety of situations. An example with real biomarker data from the Long Life Family Study shows the usefulness of the method. PMID- 27551291 TI - Introduction: Towards a Republic of Health? PMID- 27551288 TI - High-Throughput Sequencing Reveals Single Nucleotide Variants in Longer-Kernel Bread Wheat. AB - The transcriptomes of bread wheat Yunong 201 and its ethyl methanesulfonate derivative Yunong 3114 were obtained by next-sequencing technology. Single nucleotide variants (SNVs) in the wheat strains were explored and compared. A total of 5907 and 6287 non-synonymous SNVs were acquired for Yunong 201 and 3114, respectively. A total of 4021 genes with SNVs were obtained. The genes that underwent non-synonymous SNVs were significantly involved in ATP binding, protein phosphorylation, and cellular protein metabolic process. The heat map analysis also indicated that most of these mutant genes were significantly differentially expressed at different developmental stages. The SNVs in these genes possibly contribute to the longer kernel length of Yunong 3114. Our data provide useful information on wheat transcriptome for future studies on wheat functional genomics. This study could also help in illustrating the gene functions of the non-synonymous SNVs of Yunong 201 and 3114. PMID- 27551292 TI - Can Republicanism Tame Public Health? PMID- 27551293 TI - Democracy, Law and Relationships of Domination-A Response to 'Can Republicanism Tame Public Health?' AB - This brief comment responds to some of the issues raised by Daniel Weinstock's paper on the application of the republican ideal to public health. It considers the application outside of that specific context of both the problem Weinstock identifies and the solution he proposes. It queries, with reference to the different sorts of relationships of domination which exist, whether a republican approach to public health might not be better to seek to begin from private relationships of domination and to define its scope with reference to such relationships. PMID- 27551290 TI - Fulminant anaplastic large cell lymphoma (ALCL) concomitant with primary cytomegalovirus (CMV) infection, and human herpes virus 8 (HHV-8) infection together with Epstein-Barr-virus (EBV) reactivation in a patient with asymptomatic HIV-infection. AB - BACKGROUND: Most malignant lymphomas in HIV-patients are caused by reactivation of EBV-infection. Some lymphomas have a very rapid fulminant course. HHV-8 has also been reported to be a cause of lymphoma. The role of CMV in the development of lymphoma is not clear, though both CMV and HHV-8 have been reported in tissues adjacent to the tumour in Burkitt lymphoma patients. Here we present a patient with asymptomatic HIV infection, that contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. Three weeks before onset of symptoms the patient had unprotected sex which could be possible source of his CMV and also HHV-8 infection He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). METHODS: A Caucasian homosexual male with asymptomatic human immunodeficiency virus (HIV) infection contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). Clinical and laboratory records were compiled. Immunohistochemistry was performed on lymphoid tissues, a liver biopsy, a bone marrow aspirate and the spleen during the illness and at autopsy. Serology and PCR for HIV, CMV, EBV, HHV 1-3 and 6-8 was performed on blood drawn during the course of disease. RESULTS: The patient presented with an acute primary CMV infection. Biopsies taken 2 weeks before death showed a small focus of ALCL in one lymph node of the neck. Autopsy demonstrated a massive infiltration of ALCL in lymph nodes, liver, spleen and bone marrow. Blood samples confirmed primary CMV- infection, a HHV-8 infection together with reactivation of Epstein- Barr-virus (EBV). CONCLUSION: Primary CMV infection and concomitant HHV-8 infection correlated with reactivation of EBV. We propose that these two viruses influenced the development and progression of the lymphoma. Quantitative PCR blood analysis for EBV, CMV and HHV-8 could be valuable in diagnosis and treatment of this type of very rapidly developing lymphoma. It is also a reminder of the importance of prevention and prophylaxis of several infections by having protected sex. PMID- 27551294 TI - Public Health and Political Theory: The Importance of Taming Individualism. PMID- 27551295 TI - Political Theory, Values and Public Health. AB - This article offers some general criticisms of the idea that any political theory can legitimate public health interventions, and then some particular criticisms of Civic Republicanism as a political theory for public health. Civic Republicanism, I argue, legitimizes liberty-infringing public health interventions by demanding high levels of civic engagement in framing and reviewing them; to demand such engagement in pursuit of such a baseline value as health will leave insufficient civic energy for the pursuit of higher values. PMID- 27551296 TI - Republicanism and the Paradox of Public Health Preconditions Comments on Steve Latham. PMID- 27551297 TI - Public Health Interventions as Regulatory Governance: The Place of Political Theory. AB - This is a reply to Steve Latham's Article for the Republicanism special issue. PMID- 27551298 TI - Fighting Status Inequalities: Non-domination vs Non-interference. AB - Status inequalities seem to play a fairly big role in creating inequalities in health. This article assumes that there can be good reasons to fight status inequalities in order to reduce inequalities in health. It examines whether the neorepublican ideal of non-dominance does a better job as a theoretical foil for this as compared to a liberal notion of non-interference. The article concludes that there is a prima facie case for incorporating non-dominance into our thinking about public health, but that it needs to go hand in hand with a more traditional liberal ideal of non-interference. PMID- 27551299 TI - The Moral Physiology of Inequality: Response to 'Fighting Status Inequalities: Non-domination vs Non-interference'. AB - In this article, I respond to 'Fighting Status Inequalities'. I first note a niggle about the paper's assumption that lowering socio-economic inequalities will lower the social gradient in health. I then suggest two further ways in which neorepublicanism may relate to social epidemiology: in terms of 'moral physiology' and through analysing which inequalities are unjust. PMID- 27551300 TI - Commentary on Nielsen and Landes, 'Fighting Status Inequalities: Non-domination and Non-interference'. PMID- 27551301 TI - Right Relation and Right Recognition in Public Health Ethics: Thinking Through the Republic of Health. AB - The further development of public health ethics will be assisted by a more direct engagement with political theory. In this way, the moral vocabulary of the liberal tradition should be supplemented-but not supplanted-by different conceptual and normative resources available from other traditions of political and social thought. This article discusses four lines of further development that the normative conceptual discourse of public health ethics might take. (i) The relational turn. The implications for public health ethics of the new 'ecological' or 'relational' interpretation that is emerging for concepts such as agency, self-identity, autonomy, liberty and justice. (ii) Governing the health commons. The framework of collective action problems is giving way to notions of democratic governance and management of common resources. (iii) The concept of membership. Membership is specified by the notions of equal respect and parity of voice and agency. (iv) The concept of mutuality. Mutuality is specified by the notions of interdependent concern and care. PMID- 27551302 TI - Right, Well-being and the Republic of Health: A Response to Jennings. AB - This commentary offers a response to Bruce Jennings' arguments concerning republicanism and health. PMID- 27551303 TI - Comment on Jennings, 'Right Relation and Right Recognition in Public Health Ethics: Thinking through the Republic of Health'. AB - This paper offers a brief comment on Jennings' preceding paper, focusing on the capacity of a republican approach to public health ethics to facilitate reconceptualization of the right to health in situations of limited resources through a relational reading. PMID- 27551304 TI - Lifestyle Vaccines and Public Health: Exploring Policy Options for a Vaccine to Stop Smoking. AB - Experimental vaccines are being developed for the treatment of 'unhealthy lifestyles' and associated chronic illnesses. Policymakers and other stakeholders will have to deal with the ethical issues that this innovation path raises: are there morally justified reasons to integrate these innovative biotechnologies in future health policies? Should public money be invested in further research? Focusing on the case of an experimental nicotine vaccine, this article explores the ethical aspects of 'lifestyle vaccines' for public health. Based on findings from a qualitative study into a vaccine for smoking cessation, the article articulates possible value conflicts related to nicotine vaccination as an intervention in tobacco control. The 'vaccinization' of lifestyle disease piggybacks on the achievements of classic vaccines. Contrary to expectations of simplicity and success, quitting smoking with a vaccine requires a complex supportive network. Social justice and public trust may become important ethical challenges when deciding whether to use further public funds for research or whether to implement these innovative vaccines in the future. PMID- 27551305 TI - Towards a 'Sociorelational' Approach to Conceptualizing and Managing Addiction. AB - This article looks at how and why addiction should be understood as a 'sociorelational' (social and relational) disorder, and what this implies on a policy level in terms of the treatment and prevention of addiction. In light of scientific research, we argue that the neurobiological changes that underlie addiction are heavily influenced by sociorelational processes. We thereby advocate for a conceptual approach in which autonomy in addiction is a sociorelational concept, and social environments are considered autonomy undermining or autonomy promoting. We then discuss the various implications this should have on policies. PMID- 27551307 TI - Letter to the Editor: New Study Raises Questions about Effectiveness of Nicotine Replacement Therapy. PMID- 27551306 TI - Analysis of the Paternalistic Justification of an Agenda Setting Public Health Policy: The Case of Tobacco Plain Packaging. AB - This article analyses the paternalistic justification of the world's first mandatory tobacco plain packaging policy, which came into force in Australia in 2012. The policy is setting international precedence, with a range of developed and developing countries planning and implementing similar policies. Understanding the paternalistic dimension of the policy is therefore of imminent international importance. The policy meets important ethical benchmarks such as respect for citizens' self-interests and protection of others against harm. However, plain packaging faces a number of ethical challenges: the policy is a controversial type of paternalism; it runs partially against the harm principle; and it fails to meet key operational criteria. PMID- 27551308 TI - Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels. AB - BACKGROUND: Considering that vitamin A deficiency modulates hepcidin expression and consequently affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway. METHODS: Male Wistar rats were treated: control AIN-93G diet (CT), vitamin A-deficient diet (VAD), iron-deficient diet (FeD), vitamin A- and iron-deficient diet (VAFeD), or 12 mg all-trans retinoic acid (atRA)/kg diet. RESULTS: Vitamin A deficiency (VAD) increased hepatic Bmp6 and Hfe2 mRNA levels and down-regulated hepatic Hamp, Smad7, Raralpha, and intestinal Fpn1 mRNA levels compared with the control. The FeD rats showed lower hepatic Hamp, Bmp6, and Smad7 mRNA levels compared with those of the control, while in the VAFeD rats only Hamp and Smad7 mRNA levels were lower than those of the control. The VAFeD diet up-regulated intestinal Dmt1 mRNA levels in relation to those of the control. The replacement of retinyl ester by atRA did not restore hepatic Hamp mRNA levels; however, the hepatic Hfe2, Bmp6, and Smad7 mRNA levels were similar to the control. The atRA rats showed an increase of hepatic Raralpha mRNA levels and a reduction of intestinal Dmt1 mRNA and Fpn1 levels compared with those of the control. CONCLUSIONS: The HJV-BMP6-SMAD signaling pathway that normally activates the expression of hepcidin in iron deficiency is impaired by vitamin A deficiency despite increased expression of liver Bmp6 and Hfe2 mRNA levels and decreased expression of Smad7 mRNA. This response may be associated to the systemic iron deficiency and spleen iron retention promoted by vitamin A deficiency. PMID- 27551309 TI - Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes. AB - BACKGROUND: TCF7L2 is a central transcription factor in the canonical wingless type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence. RESULTS: We included 26,905 individuals without diabetes from the Malmo Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including TCF7L2 (rs7903146 and rs12255372), HHEX (rs1111875), HNF1A (rs7957197), NOTCH2 (rs10923931), TLE4 (rs13292136), ZBED3 (rs4457053), and PPARG (rs1801282 and rs13081389). SNPs in TCF7L2, NOTCH2, and ZBED3 showed significant interactions with fiber intake on type 2 diabetes incidence (P interaction = 0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the TCF7L2 risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the NOTCH2 variant and homozygotes of the risk allele of the ZBED3 variant. CONCLUSIONS: Our results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence. PMID- 27551310 TI - Circulating microRNAs are deregulated in overweight/obese children: preliminary results of the I.Family study. AB - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs involved in the modulation of gene expression and in the control of numerous cell functions. Alterations of miRNA patterns frequently occur in cancer and metabolic disorders, including obesity. Recent studies showed remarkable stability of miRNAs in both plasma and serum making them suitable as potential circulating biomarkers for a variety of diseases and conditions. The aim of this study was to assess the profile of circulating miRNAs expressed in plasma samples of overweight or obese (OW/Ob) and normal weight (NW) prepubertal children from a European cohort (www.ifamilystudy.eu). The project, aimed to assess the determinants of eating behavior in children and adolescents of eight European countries, is built on the IDEFICS cohort (www.ideficsstudy.eu), established in 2006. Among the participants of the I.Family Italian Cohort, ten OW/Ob (age 10.7 +/- 1.5 years, BMI 31.6 +/- 4.3 kg/m(2)) and ten NW (age 10.5 +/- 2.7 years, BMI 16.4 +/- 1.7 kg/m(2)) children were selected for the study. Gene arrays were employed to differentially screen the expression of 372 miRNAs in pooled plasma samples. Deregulated miRNAs (p < 0.05) were further validated in the individual samples using a real-time PCR (RT-qPCR) approach. RESULTS: Using a significance threshold of p < 0.05 and a fold-change threshold of +/- 4.0, we preliminarily identified in the pooled samples eight miRNAs that differed between the OW/Ob and NW groups. The validation by RT-qPCR in the individual plasma samples showed a twofold upregulation of miR-31-5p, a threefold upregulation of miR-2355-5p, and a 0.5 fold downregulation of miR-206 in OW/Ob as compared with NW. The molecular functions of these differentially expressed plasma miRNAs as well as their expected mRNA targets were predicted by bioinformatics tools. CONCLUSIONS: This pilot study shows that three circulating miRNAs are differentially regulated in OW/Ob as compared with NW children. Although causal pathways cannot be firmly inferred by these results, that deserve confirmation in larger samples, it is conceivable that circulating miRNAs may be novel biomarkers of obesity and related metabolic disturbances. PMID- 27551311 TI - Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats. AB - BACKGROUND: Emerging evidence suggests beneficial effects of omega-3 fatty acids on diabetic complications. The present study compared the progressive effects of metformin and flax/fish oil on lipid metabolism, inflammatory markers, and liver and renal function test markers in streptozotocin-nicotinamide-induced diabetic rats. METHODS: Streptozotocin-induced diabetic rats were randomized into control and four diabetic groups: streptozotocin (STZ), metformin (200 mg/kg body weight (b.w)/day (D)), flax and fish oil (500 mg/kg b.w/D). RESULTS: Metformin and flax and fish oil exhibited increased expression of transcription factor peroxisome proliferator-activated receptor gamma while the treatment downregulated sterol regulatory element-binding protein 1 and nuclear factor kbeta as compared to those of the STZ group. Apart from modulation of transcription factor expression, the expression of fatty acid synthase, long chain acyl CoA synthase, and malonyl CoA-acyl carrier protein transacylase was lowered by flax/fish oil treatment. Serum cholesterol, triglycerides, and VLDL were also significantly reduced in the treatment groups as compared to those in the STZ group. Although pathological abnormalities were seen in the liver and kidneys of rats on metformin, no significant changes in liver/renal function markers were observed at day 15 and day 30 of the treatment groups. Flax/fish oil had protective effects toward pathological abnormalities in the liver and kidney. Flax/fish oil improved lipid profile and alkaline phosphatase at day 30 as compared to that at day 15. CONCLUSIONS: The present study demonstrates potential beneficial effects of metformin and flax/fish oil intervention in improving serum lipid profile by regulating the expression of transcription factors and genes involved in lipid metabolism in diabetic rats. In addition, these interventions also lowered the expression of atherogenic cytokines. The protective effects of flax/fish oil are worth investigating in human subjects on metformin monotherapy. PMID- 27551312 TI - Erratum to: The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels. AB - [This corrects the article DOI: 10.1007/s12263-014-0388-4.]. PMID- 27551314 TI - Differences in genome-wide gene expression response in peripheral blood mononuclear cells between young and old men upon caloric restriction. AB - BACKGROUND: Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. Only a limited number of CR studies have been performed on humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a completely controlled 30 % CR diet on immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-28, and nine healthy old men, aged 64-85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. Before and after 30 % CR, the whole genome gene expression in peripheral blood mononuclear cells (PBMCs) was assessed. RESULTS: Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling the immune response. CONCLUSIONS: Based on the gene expression data, we theorise that a short period of CR is not effective in old men regarding immune-related pathways while it is effective in young men. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00561145. PMID- 27551315 TI - Liver-specific NG37 overexpression leads to diet-dependent fatty liver disease accompanied by cardiac dysfunction. AB - BACKGROUND: Environmental factors are well-known causes of diseases. However, aside from a handful of risk indicators, genes' encoding susceptibility to chronic illnesses and their associated environmental triggers are largely unknown. In this era of increasingly rich diets, such genetic predispositions would be immensely helpful from a public health perspective. The novel transgenic mouse model with liver-specific NG37 overexpression characterized in this article identifies the diet-dependent function of NG37 in the pathogenesis of fatty liver disease and cardiac arrhythmia. RESULTS: The liver-specific NG37 overexpression transgenic mouse model described here was generated using the Alb-SV40 polyA expression plasmid backbone. NG37 cDNA under control of the albumin promoter for liver-specific expression was fused with a 5' terminal M2 FLAG sequence and a SV40 early region transcription terminator/polyadenylation site attached at the 3'-UTR. These NG37 transgenic mice developed normally and were physiologically normal on a standard diet. However, in comparison to non-transgenic (nTG) litter mates, these mice develop dramatic phenotypes within 12-18 days of starting a high-fat diet: (i) increased body weight (28.5 +/- 12.3 g), (ii) increased liver weight (87.4 +/- 35.7 mg), (iii) increased heart weight (140 +/- 38.4 mg), and (iv) cardiac arrhythmia. The enlarged livers of high-fat diet NG37 transgenic mice was histologically similar to human fatty liver disease and contained Maltese cross birefringent active depositions in hepatocytes that are indicative of fatty liver disease. We also confirmed via X-ray diffraction the steatotic vesicles in the diseased hepatocytes of our high-fat diet NG37 mice was composed of cholesteryl derivatives also found in human fatty liver disease. In addition to cardiac enlargement, NG37 transgenic mice on high-fat diet also exhibited highly irregular bradycardia not present in either high-fat diet nTG littermates or normal-diet transgenic litter mates. CONCLUSIONS: The dramatic high-fat diet dependent symptoms (increased body weight, cardiac enlargement, fatty liver, and cardiac arrhythmias) characterized in our liver-specific NG37 overexpression mouse model identifies NG37 as a gene encoding latent lipid metabolism pathology induced only in the presence of an environmental factor relevant to human health: high-fat diet. PMID- 27551316 TI - Ancient pathogen-driven adaptation triggers increased susceptibility to non celiac wheat sensitivity in present-day European populations. AB - BACKGROUND: Non-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones. METHODS: To explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci. RESULTS: Our results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression. CONCLUSIONS: This led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies. PMID- 27551313 TI - Biomarkers for nutrient intake with focus on alternative sampling techniques. AB - Biomarkers of nutrient intake or nutrient status are important objective measures of foods/nutrients as one of the most important environmental factors people are exposed to. It is very difficult to obtain accurate data on individual food intake, and there is a large variation of nutrient composition of foods consumed in a population. Thus, it is difficult to obtain precise measures of exposure to different nutrients and thereby be able to understand the relationship between diet, health, and disease. This is the background for investing considerable resources in studying biomarkers of nutrients believed to be important in our foods. Modern technology with high sensitivity and specificity concerning many nutrient biomarkers has allowed an interesting development with analyses of very small amounts of blood or tissue material. In combination with non-professional collection of blood by finger-pricking and collection on filters or sticks, this may make collection of samples and analyses of biomarkers much more available for scientists as well as health professionals and even lay people in particular in relation to the marked trend of self-monitoring of body functions linked to mobile phone technology. Assuming standard operating procedures are used for collection, drying, transport, extraction, and analysis of samples, it turns out that many analytes of nutritional interest can be measured like metabolites, drugs, lipids, vitamins, minerals, and many types of peptides and proteins. The advantage of this alternative sampling technology is that non-professionals can collect, dry, and mail the samples; the samples can often be stored under room temperature in a dry atmosphere, requiring small amounts of blood. Another promising area is the potential relation between the microbiome and biomarkers that may be measured in feces as well as in blood. PMID- 27551317 TI - The PBMC transcriptome profile after intake of oxidized versus high-quality fish oil: an explorative study in healthy subjects. AB - BACKGROUND: Marine long-chain polyunsaturated fatty acids are susceptible to oxidation, generating a range of different oxidation products with suggested negative health effects. The aim of the present study was to utilize sensitive high-throughput transcriptome analyses to investigate potential unfavorable effects of oxidized fish oil (PV: 18 meq/kg; AV: 9) compared to high-quality fish oil (PV: 4 meq/kg; AV: 3). METHODS: In a double-blinded randomized controlled study for seven weeks, 35 healthy subjects were assigned to 8 g of either oxidized fish oil or high quality fish oil. The daily dose of EPA+DHA was 1.6 g. Peripheral blood mononuclear cells were isolated at baseline and after 7 weeks and transcriptome analyses were performed with the illuminaHT-12 v4 Expression BeadChip. RESULTS: No gene transcripts, biological processes, pathway or network were significantly changed in the oxidized fish oil group compared to the fish oil group. Furthermore, gene sets related to oxidative stress and cardiovascular disease were not differently regulated between the groups. Within group analyses revealed a more prominent effect after intake of high quality fish oil as 11 gene transcripts were significantly (FDR < 0.1) changed from baseline versus three within the oxidized fish oil group. CONCLUSION: The suggested concern linking lipid oxidation products to short-term unfavorable health effects may therefore not be evident at a molecular level in this explorative study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01034423. PMID- 27551318 TI - Dibutyryl-cAMP affecting fat deposition of finishing pigs by decreasing the inflammatory system related to insulin sensitive or lipolysis. AB - BACKGROUND: The mechanism of db-cAMP regulating fat deposition and improving lean percentage is unclear and needs to be further studied. METHODS: Eighteen 100-day old Duroc * Landrance * Large White barrows (49.75 +/- 0.75 kg) were used for experiment 1, and 15 eighteen 135-day-old barrows (78.34 +/- 1.22 kg) were used for experiment 2 to investigate the effects of dietary dibutyryl-cAMP (db-cAMP) on fat deposition in finishing pigs. Pigs were fed with a corn-soybean meal-based diet supplemented with 0 or 15 mg/kg db-cAMP, and both experiments lasted 35 days, respectively. RESULTS: The results showed that db-cAMP decreased the backfat thickness, backfat percentage, and diameter of backfat cells without changing the growth performance or carcass characteristics in both experiments, and this effect was more marked in experiment 1 than in experiment 2; db-cAMP enhanced the activity of the growth hormone-insulin-like growth factor-1 (GH-IGF 1) axis and pro-opiomelanocortin (POMC) system in both experiments, which suppressed the accumulation of backfat deposition; microarray analysis showed that db-cAMP suppressed the inflammatory system within the adipose tissue related to insulin sensitivity, which also reduced fat synthesis. CONCLUSIONS: In summary, the effect of db-cAMP on suppressing fat synthesis and accumulation is better in the earlier phase than in the later phase of finishing pigs, and db cAMP plays this function by increasing the activity of the GH-IGF-1 axis and POMC system, while decreasing the inflammatory system within the adipose tissue related to insulin sensitive or lipolysis. PMID- 27551319 TI - Metallothioneins 1 and 2, but not 3, are regulated by nutritional status in rat white adipose tissue. AB - BACKGROUND: Cumulating evidence underlines the role of adipose tissue metallothionein (MT) in the development of obesity and type 2 diabetes. Fasting/refeeding was shown to affect MT gene expression in the rodent liver. The influence of nutritional status on MT gene expression in white adipose tissue (WAT) is inconclusive. The aim of this study was to verify if fasting and fasting/refeeding may influence expression of MT genes in WAT of rats. RESULTS: Fasting resulted in a significant increase in MT1 and MT2 gene expressions in retroperitoneal, epididymal, and inguinal WAT of rats, and this effect was reversed by refeeding. Altered expressions of MT1 and MT2 genes in all main fat depots were reflected by changes in serum MT1 and MT2 levels. MT1 and MT2 messenger RNA (mRNA) levels in WAT correlated inversely with serum insulin concentration. Changes in MT1 and MT2 mRNA levels were apparently not related to total zinc concentrations and MTF1 and Zn transporter mRNA levels in WAT. Fasting or fasting/refeeding exerted no effect on the expression of MT3 gene in WAT. Addition of insulin to isolated adipocytes resulted in a significant decrease in MT1 and MT2 gene expressions. In contrast, forskolin or dibutyryl-cAMP (dB-cAMP) enhanced the expressions of MT1 and MT2 genes in isolated adipocytes. Insulin partially reversed the effect of dB-cAMP on MT1 and MT2 gene expressions. CONCLUSIONS: This study showed that the expressions of MT1 and MT2 genes in WAT are regulated by nutritional status, and the regulation may be independent of total zinc concentration. PMID- 27551320 TI - Moderately decreased maternal dietary energy intake during pregnancy reduces fetal skeletal muscle mitochondrial biogenesis in the pigs. AB - BACKGROUND: Mitochondria are of major importance in oocyte and early embryo, playing a key role in maintaining energy homeostasis. Epidemiological findings indicate that maternal undernutrition-induced mitochondrial dysfunction during pregnancy is associated with the development of metabolic disorders in offspring. Here, we investigated the effects of moderately decreased maternal energy intake during pregnancy on skeletal muscle mitochondrial biogenesis in fetal offspring with pig as a model. METHODS: Pregnant Meishan sows were allocated to a standard energy (SE) intake group as recommended by the National Research Council (NRC; 2012) and a low-energy (LE) intake group. Fetal umbilical vein serum and longissimus muscle samples were collected for further analysis on day 90 of pregnancy. RESULTS: Sow and fetal weights and the concentrations of serum growth hormone (GH) and glucose were reduced in LE group. Maternal LE diet decreased the messenger RNA (mRNA) expression of genes involved in mitochondrial biogenesis and function such as peroxisome proliferator-activated receptor gamma coactivator 1alpha (PPARGC1A), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), beta subunit of mitochondrial H(+)-ATP synthase (ATB5B), sirtuin 1 (Sirt1), and citrate synthase (CS). The protein expression of PPARGC1A and Sirt1, intracellular NAD(+)-to-NADH ratio, and CS activity was reduced in LE group, and accordingly, mitochondrial DNA (mtDNA) content was decreased. Moreover, copper/zinc superoxide dismutase (CuZn-SOD) expression at both mRNA and protein levels and SOD and catalase (CAT) activities were reduced in LE group as well. CONCLUSIONS: The observed decrease in muscle mitochondrial biogenesis and antioxidant defense capacity suggests that moderately decreased maternal energy intake during pregnancy impairs mitochondrial function in fetal pigs. PMID- 27551321 TI - Genetic susceptibility to dyslipidemia and incidence of cardiovascular disease depending on a diet quality index in the Malmo Diet and Cancer cohort. AB - BACKGROUND: By taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk. METHODS: We included 24,799 participants (62 % women, age 44-74 years) from the Malmo Diet and Cancer cohort. During a mean follow-up time of 15 years, 3068 incident CVD cases (1814 coronary and 1254 ischemic stroke) were identified. Genetic risk scores (GRSs) were constructed by combining 80 validated genetic variants associated with higher TG and LDL-C or lower HDL-C. The participants' dietary intake, assessed by a modified diet history method, was ranked according to a diet quality index that included six dietary components: saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose. RESULTS: The GRSLDL-C (P = 5 * 10(-6)) and GRSHDL-C (P = 0.02) but not GRSTG (P = 0.08) were significantly associated with CVD risk. No significant interaction between the GRSs and diet quality was observed on CVD risk (P > 0.39). A high compared to a low diet quality attenuated the association between GRSLDL-C and the risk of incident ischemic stroke (P interaction = 0.01). CONCLUSION: We found some evidence of an interaction between diet quality and GRSLDL-C on ischemic stroke. PMID- 27551322 TI - Coordinated regulation of hepatic and adipose tissue transcriptomes by the oral administration of an amino acid mixture simulating the larval saliva of Vespa species. AB - BACKGROUND: VAAM is an amino acid mixture that simulates the composition of Vespa larval saliva. VAAM enhanced physical endurance of mice and have been used by athletes as a supplementary drink before exercise. However, there is no information on the effect of VAAM on the physiology of freely moving animals. The purpose of this study was to obtain information about the VAAM-dependent regulation of liver and adipose tissue transcriptomes. RESULTS: Mice were orally fed a VAAM solution, an amino acid mixture mimicking casein hydrolysate (CAAM) or water under ad libitum feeding conditions for 5 days. Comparisons of the hepatic transcriptome between VAAM-, CAAM-, and water-treated groups revealed a VAAM specific regulation of the metabolic pathway, i.e., the down-regulation of glycolysis and fatty acid oxidation and the up-regulation of polyunsaturated fatty acid synthesis and glucogenic amino acid utilization. Similar transcriptomic analyses of white and brown adipose tissues (WAT and BAT, respectively) indicated the up-regulation of phospholipid synthesis in WAT and the negative regulation of cellular processes in BAT. Because the coordinated regulation of tissue transcriptomes implied the presence of upstream signaling common to these tissues, we conducted an Ingenuity Pathways Analysis. This analysis showed that estrogenic and glucagon signals were activated in the liver and WAT and that beta-adrenergic signaling was activated in all three tissues. CONCLUSIONS: We found that VAAM ingestion had an effect on multiple tissue transcriptomes of freely moving mice. Utilization of glycogenic amino acids may have been activated in the liver. Fatty acid conversion into phospholipid, not to triacylglycerol, may have been stimulated in adipocytes contrasting that a little effect was observed in BAT. Analysis of upstream factors revealed that multiple hormonal signals were activated in the liver, WAT, and BAT. Our data provide some clues to understanding the role of VAAM in metabolic regulation. PMID- 27551325 TI - A Summary of a Cochrane Review: Supplementation with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and development. PMID- 27551324 TI - Protein-DNA and ion-DNA interactions revealed through contrast variation SAXS. AB - Understanding how DNA carries out its biological roles requires knowledge of its interactions with biological partners. Since DNA is a polyanionic polymer, electrostatic interactions contribute significantly. These interactions are mediated by positively charged protein residues or charge compensating cations. Direct detection of these partners and/or their effect on DNA conformation poses challenges, especially for monitoring conformational dynamics in real time. Small angle x-ray scattering (SAXS) is uniquely sensitive to both the conformation and local environment (i.e. protein partner and associated ions) of the DNA. The primary challenge of studying multi-component systems with SAXS lies in resolving how each component contributes to the measured scattering. Here, we review two contrast variation (CV) strategies that enable targeted studies of the structures of DNA or its associated partners. First, solution contrast variation enables measurement of DNA conformation within a protein-DNA complex by masking out the protein contribution to the scattering profile. We review a specific example, in which the real-time unwrapping of DNA from a nucleosome core particle is measured during salt-induced disassembly. The second method, heavy atom isomorphous replacement, reports the spatial distribution of the cation cloud around duplex DNA by exploiting changes in the scattering strength of cations with varying atomic numbers. We demonstrate the application of this approach to provide the spatial distribution of monovalent cations (Na+, K+, Rb+, Cs+) around a standard 25-base pair DNA. The CV strategies presented here are valuable tools for understanding DNA interactions with its biological partners. PMID- 27551326 TI - Advancing X-ray scattering metrology using inverse genetic algorithms. AB - We compare the speed and effectiveness of two genetic optimization algorithms to the results of statistical sampling via a Markov chain Monte Carlo algorithm to find which is the most robust method for determining real space structure in periodic gratings measured using critical dimension small angle X-ray scattering. Both a covariance matrix adaptation evolutionary strategy and differential evolution algorithm are implemented and compared using various objective functions. The algorithms and objective functions are used to minimize differences between diffraction simulations and measured diffraction data. These simulations are parameterized with an electron density model known to roughly correspond to the real space structure of our nanogratings. The study shows that for X-ray scattering data, the covariance matrix adaptation coupled with a mean absolute error log objective function is the most efficient combination of algorithm and goodness of fit criterion for finding structures with little foreknowledge about the underlying fine scale structure features of the nanograting. PMID- 27551323 TI - Fatty acid extract from CLA-enriched egg yolks can mediate transcriptome reprogramming of MCF-7 cancer cells to prevent their growth and proliferation. AB - BACKGROUND: Our previous study showed that fatty acids extract obtained from CLA enriched egg yolks (EFA-CLA) suppressed the viability of MCF-7 cancer cell line more effectively than extract from non-enriched egg yolks (EFA). In this study, we analysed the effect of EFA-CLA and EFA on transcriptome profile of MCF-7 cells by applying the whole Human Genome Microarray technology. RESULTS: We found that EFA-CLA and EFA treated cells differentially regulated genes involved in cancer development and progression. EFA-CLA, compared to EFA, positively increased the mRNA expression of TSC2 and PTEN tumor suppressors as well as decreased the expression of NOTCH1, AGPS, GNA12, STAT3, UCP2, HIGD2A, HIF1A, PPKAR1A oncogenes. CONCLUSIONS: We show for the first time that EFA-CLA can regulate genes engaged in AKT/mTOR pathway and inhibiting cell cycle progression. The observed results are most likely achieved by the combined effect of both: incorporated CLA isomers and other fatty acids in eggs organically modified through hens' diet. Our results suggest that CLA-enriched eggs could be easily available food products with a potential of a cancer chemopreventive agent. PMID- 27551327 TI - Dissemination of definitions and concepts of allergic and hypersensitivity conditions. AB - BACKGROUND: Allergy and hypersensitivity can affect people of any age and manifest with problems in a range of organ systems. Moreover, they can have a significant impact on the quality of life of patients and their families. Although once rare, there is presently an epidemic of allergic disorders with associated considerable societal consequences. Our understanding of the pathophysiology of these disorders has changed substantially over the last 20 years. In the light of these developments, the Joint Allergy Academies have made concerted efforts to ensure that these are reflected in the current definitions and concepts used in clinical allergy and to ensure these are reflected in the forthcoming International Classification of Diseases-11 (ICD-11). OBJECTIVE: In this review, we seek to provide an update on the current definitions and concepts in relation to allergic disorders. RESULTS: Once the new section has been built in the ICD-11 to address allergic and hypersensitivity conditions, we have been moving actions to try to support awareness by disseminating updated concepts in the field. Aligned with the ICD and the WAO philosophy of being global, this document presents fundamental and broad allergy concepts to strengthen the understanding by different health professionals worldwide, besides to support the formation of in training students. CONCLUSION: This current review intends to be accepted and used universally by all health professionals involved in diseases' classification and coding and, therefore, contribute to improve care and outcomes in this increasing sub-section of the world's population. PMID- 27551329 TI - Immigrants Equilibrate Local Labor Markets: Evidence from the Great Recession. AB - This paper demonstrates that low-skilled Mexican-born immigrants' location choices in the U.S. respond strongly to changes in local labor demand, and that this geographic elasticity helps equalize spatial differences in labor market outcomes for low-skilled native workers, who are much less responsive. We leverage the substantial geographic variation in employment losses that occurred during Great Recession, and our results confirm the standard finding that high skilled populations are quite geographically responsive to employment opportunities while low-skilled populations are much less so. However, low skilled immigrants, especially those from Mexico, respond even more strongly than high-skilled native-born workers. Moreover, we show that natives living in metro areas with a substantial Mexican-born population are insulated from the effects of local labor demand shocks compared to those in places with few Mexicans. The reallocation of the Mexican-born workforce reduced the incidence of local demand shocks on low-skilled natives' employment outcomes by more than 50 percent. PMID- 27551330 TI - A chemoproteomic method for identifying cellular targets of covalent kinase inhibitors. AB - Protein kinases are attractive drug targets for numerous human diseases including cancers, diabetes and neurodegeneration. A number of kinase inhibitors that covalently target a cysteine residue in their target kinases have recently entered use in the cancer clinic. Despite the advantages of covalent kinases inhibitors, their inherent reactivity can lead to non-specific binding to other cellular proteins and cause off- target effects in cells. It is thus essential to determine the identity of these off targets in order to fully account for the phenotype and to improve the selectivity and efficacy of covalent inhibitors. Herein we present a detailed protocol for a chemoproteomic method to enrich and identify cellular targets of covalent kinase inhibitors. PMID- 27551328 TI - The use of inhaled corticosteroids in pediatric asthma: update. AB - Despite the availability of several formulations of inhaled corticosteroids (ICS) and delivery devices for treatment of childhood asthma and despite the development of evidence-based guidelines, childhood asthma control remains suboptimal. Improving uptake of asthma management plans, both by families and practitioners, is needed. Adherence to daily ICS therapy is a key determinant of asthma control and this mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices. The potential adverse effects of ICS need to be weighed against the benefit of these drugs to control persistent asthma especially that its safety profile is markedly better than oral glucocorticoids. This article reviews the key mechanisms of inhaled corticosteroid action; recommendations on dosage and therapeutic regimens; potential optimization of effectiveness by addressing inhaler technique and adherence to therapy; and updated knowledge on the real magnitude of adverse events. PMID- 27551331 TI - MUC4 is negatively regulated through the Wnt/beta-catenin pathway via the Notch effector Hath1 in colorectal cancer. AB - MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/beta-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by beta-catenin in CRC. We first knocked down (KD) beta-catenin in three CRC cell lines; LS180, HCT-8 and HCT116, which resulted in increased MUC4 transcript and MUC4 protein. Additionally, the overexpression of stabilized mutant beta-catenin in LS180 and HCT-8 resulted in a decrease in MUC4 expression. Immunohistochemistry (IHC) of mouse colon tissue harboring tubular adenomas and high grade dysplasia showed dramatically reduced Muc4 in lesions relative to adjacent normal tissue, with increased cytosolic/nuclear beta-catenin. Luciferase assays with the complete MUC4 promoter construct p3778 showed increased MUC4 promoter luciferase activity in the absence of beta-catenin (KD). Mutation of all three putative TCF/LEF sites showed that MUC4 promoter luciferase activity was increased relative to the un-mutated promoter. Interestingly, it was observed that MUC4 expressing CRC cell lines also expressed high levels of Hath1, a transcription factor repressed by both active Wnt/beta-catenin and Notch signaling. The KD of beta-catenin and/or treatment with a Notch gamma-secretase inhibitor, Dibenzazepine (DBZ) resulted in increased Hath1 and MUC4 in LS180, HCT 8 and HCT116. Furthermore, overexpression of Hath1 in HCT-8 and LS180 caused increased MUC4 transcript and MUC4 protein. Taken together, our results indicate that the Wnt/beta-catenin pathway suppresses the Notch pathway effector Hath1, resulting in reduced MUC4 in CRC. PMID- 27551332 TI - Short-form Ron is a novel determinant of ovarian cancer initiation and progression. AB - Short-form Ron (sfRon) is an understudied, alternative isoform of the full-length Ron receptor tyrosine kinase. In contrast to Ron, which has been shown to be an important player in many cancers, little is known about the role of sfRon in cancer pathogenesis. Here we report the striking discovery that sfRon expression is required for development of carcinogen-induced malignant ovarian tumors in mice. We also show that sfRon is expressed in several subtypes of human ovarian cancer including high-grade serous carcinomas, which is in contrast to no detectable expression in healthy ovaries. In addition, we report that introduction of sfRon into OVCAR3 cells resulted in epithelial-to-mesenchymal transition, activation of the PI3K and PDK1 pathway, and inhibition of the MAPK pathway. We demonstrated that sfRon confers an aggressive cancer phenotype in vitro characterized by increased proliferation and migration, and decreased adhesion of ovarian cancer cells. Moreover, the in vivo studies show that OVCAR3 tumors expressing sfRon exhibit significantly more robust growth and spreading to the abdominal cavity when compared with the parental sfRon negative OVCAR3 cells. These data suggest that sfRon plays a significant role in ovarian cancer initiation and progression, and may represent a promising therapeutic target for ovarian cancer treatment. PMID- 27551334 TI - Combination of JAK2 and HSP90 inhibitors: an effective therapeutic option in drug resistant chronic myelogenous leukemia. AB - Recent studies suggest that JAK2 serves as a novel therapeutic target in Bcr-Abl+ chronic myelogenous leukemia (CML). We have reported the existence of an HSP90- associated high molecular weight network complex (HMWNC) that is composed of HSP90 client proteins BCR-ABL, JAK2, and STAT3 in wild type Bcr-Abl+ leukemic cells. Here we showed that the HSP90-HMWNC is present in leukemia cells from CML patients in blast stage, and in Imatinib (IM)-resistant 32Dp210 (T315I) leukemia cells. We found that the HSP90-HMWNC could be disassembled by depleting JAK2 with either Jak2-specific shRNA or treatment with JAK2 inhibitors (TG101209 or Ruxolitinib) and HSP90 inhibitor (AUY922). Combinational treatment with JAK2 and HSP90 inhibitors diminished the activation of BCR-ABL, JAK2 and its downstream targets. As a result, the IM-resistant 32Dp210 T315I cells underwent apoptosis. When administered in mice bearing 32Dp210 T315I leukemia, combinational therapy using Ruxolitinib and AUY922 prolonged the survival significantly. Thus, a combination of JAK2 and HSP90 inhibitors could be a powerful strategy for the treatment of CML, especially in IM-resistant patients. PMID- 27551333 TI - Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine. AB - While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events. PMID- 27551335 TI - Melatonin decreases estrogen receptor binding to estrogen response elements sites on the OCT4 gene in human breast cancer stem cells. AB - Cancer stem cells (CSCs) pose a challenge in cancer treatment, as these cells can drive tumor growth and are resistant to chemotherapy. Melatonin exerts its oncostatic effects through the estrogen receptor (ER) pathway in cancer cells, however its action in CSCs is unclear. Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERalpha) in breast cancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 MUM of the environmental estrogen Bisphenol A (BPA) and 1 mM of melatonin. At the end, the cell growth as well as OCT4 and ERalpha expression and the binding activity of ERalpha to the OCT4 was assessed. The increase in number and size of mammospheres induced by E2 or BPA was reduced by melatonin treatment. Furthermore, binding of the ERalpha to OCT4 was reduced, accompanied by a reduction of OCT4 and ERalpha expression. Thus, melatonin treatment is effective against proliferation of BCSCs in vitro and impacts the ER pathway, demonstrating its potential therapeutic use in breast cancer. PMID- 27551338 TI - Correlation of magnetic resonance signal characteristics and perfusion parameters assessed by volume perfusion computed tomography in hepatocellular carcinoma: Impact on lesion characterization. AB - AIM: To find out if magnetic resonance (MR)-signal characteristics of hepatocellular carcinomas (HCC) correlate with perfusion parameters assessed by volume perfusion computed tomography (VPCT). METHODS: From October 2009 to January 2014, 26 (mean age, 69.3 years) patients with 36 HCC lesions who underwent both VPCT and MR liver imaging were analysed. We compared signal intensity in the T1w- and T2w-images and wash-in/wash-out kinetics on post contrast MR images with mean values of blood flow (BF, mL/100 mL per minute), blood volume (BV, mL/100 mL), k-trans (mL/100 mL per minute), arterial liver perfusion (mL/100 mL per minute), portal venous perfusion and hepatic perfusion index (HPI, %) obtained by VPCT. Signal intensity on magnetic resonance imaging (MRI) was classified hyper/iso/hypointense compared with surrounding liver parenchyma. RESULTS: Signal intensity on native T1w- and T2w-images was hyper/iso/hypo in 4/16/16 and 21/14/1 lesions, respectively. Wash-in and wash-out contrast kinetics were found on MRI in 33 of 36 lesions (91.7%) and 25 of 36 lesions (69.4%), respectively. The latter was observed significantly more often in higher graded lesions (P < 0.005). HPI was 94.7% +/- 6.5%. There was no significant relationship between lesion's MR-signal intensity, MR signal combinations, size and any of the VPCT-perfusion parameters. However HPI was constantly high in all HCC lesions. CONCLUSION: VPCT parameters add limited value to MR-lesion characterization. However in HCC lesions with atypical MR signal characteristics HPI can add a parameter to ensure HCC diagnosis. PMID- 27551336 TI - Abdominal ultrasonography of the pediatric gastrointestinal tract. AB - Ultrasound is an invaluable imaging modality in the evaluation of pediatric gastrointestinal pathology; it can provide real-time evaluation of the bowel without the need for sedation or intravenous contrast. Recent improvements in ultrasound technique can be utilized to improve detection of bowel pathology in children: Higher resolution probes, color Doppler, harmonic and panoramic imaging are excellent tools in this setting. Graded compression and cine clips provide dynamic information and oral and intravenous contrast agents aid in detection of bowel wall pathology. Ultrasound of the bowel in children is typically a targeted exam; common indications include evaluation for appendicitis, pyloric stenosis and intussusception. Bowel abnormalities that are detected prenatally can be evaluated after birth with ultrasound. Likewise, acquired conditions such as bowel hematoma, bowel infections and hernias can be detected with ultrasound. Rare bowel neoplasms, vascular disorders and foreign bodies may first be detected with sonography, as well. At some centers, comprehensive exams of the gastrointestinal tract are performed on children with inflammatory bowel disease and celiac disease to evaluate for disease activity or to confirm the diagnosis. The goal of this article is to review up-to-date imaging techniques, normal sonographic anatomy, and characteristic sonographic features of common and uncommon disorders affecting the gastrointestinal tract in children. PMID- 27551337 TI - Current tecniques and new perpectives research of magnetic resonance enterography in pediatric Crohn's disease. AB - Crohn's disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past two decades. The endoscopy with biopsy is generally considered the diagnostic reference standard, this combination can evaluates only the mucosa, not inflammation or fibrosis in the mucosa. Actually, the only modalities that can visualize submucosal tissues throughout the small bowel are the computed tomography (CT) enterography (CTE) with the magnetic resonance enterography (MRE). CT generally is highly utilized, but there is growing concern over ionizing radiation and cancer risk; it is a very important aspect to keep in consideration in pediatric patients. In contrast to CTE, MRE does not subject patients to ionizing radiation and can be used to detect detailed morphologic information and functional data of bowel disease, to monitor the effects of medical therapy more accurately, to detect residual active disease even in patients showing apparent clinical resolution and to guide treatment more accurately. PMID- 27551339 TI - Value of liver computed tomography with iodixanol 270, 80 kVp and iterative reconstruction. AB - AIM: To evaluate the image quality of hepatic multidetector computed tomography (MDCT) with dynamic contrast enhancement. METHODS: It uses iodixanol 270 mg/mL (Visipaque 270) and 80 kVp acquisitions reconstructed with sinogram affirmed iterative reconstruction (SAFIRE((r))) in comparison with a standard MDCT protocol. Fifty-three consecutive patients with known or suspected hepatocellular carcinoma underwent 55 CT examinations, with two different four-phase CT protocols. The first group of 30 patients underwent a standard 120 kVp acquisition after injection of Iohexol 350 mg/mL (Accupaque 350((r))) and reconstructed with filtered back projection. The second group of 25 patients underwent a dual-energy CT at 80-140 kVp with iodixanol 270. The 80 kVp component of the second group was reconstructed iteratively (SAFIRE((r))-Siemens). All hyperdense and hypodense hepatic lesions >= 5 mm were identified with both protocols. Aorta and portal vessels/liver parenchyma contrast to noise ratio (CNR) in arterial phase, hypervascular lesion/liver parenchyma CNR in arterial phase, hypodense lesion/liver parenchyma CNR in portal and late phase were calculated in both groups. RESULTS: Aorta/liver and focal lesions altogether/liver CNR were higher for the second protocol (P = 0.0078 and 0.0346). Hypervascular lesions/liver CNR was not statistically different (P = 0.86). Hypodense lesion/liver CNR in the portal phase was significantly higher for the second group (P = 0.0107). Hypodense lesion/liver CNR in the late phase was the same for both groups (P = 0.9926). CONCLUSION: MDCT imaging with 80 kVp with iterative reconstruction and iodixanol 270 yields equal or even better image quality. PMID- 27551340 TI - 3T magnetic resonance neurography of pudendal nerve with cadaveric dissection correlation. AB - AIM: To evaluate the pudendal nerve segments that could be identified on magnetic resonance neurography (MRN) before and after surgical marking of different nerve segments. METHODS: The hypothesis for this study was that pudendal nerve and its branches would be more easily seen after the surgical nerve marking. Institutional board approval was obtained. One male and one female cadaver pelvis were obtained from the anatomy board and were scanned using 3 Tesla MRI scanner using MR neurography sequences. All possible pudendal nerve branches were identified. The cadavers were then sent to the autopsy lab and were surgically dissected by a peripheral nerve surgeon and an anatomist to identify the pudendal nerve branches. Radiological markers were placed along the course of the pudendal nerve and its branches. The cadavers were then closed and rescanned using the same MRN protocol as the pre-marking scan. The remaining pudendal nerve branches were attempted to be identified using the radiological markers. All scans were read by an experienced musculoskeletal radiologist. RESULTS: The pre-marking MR Neurography scans clearly showed the pudendal nerve at its exit from the lumbosacral plexus in the sciatic notch, at the level of the ischial spine and in the Alcock's Canal in both cadavers. Additionally, the right hemorrhoidal branch could be identified in the male pelvis cadaver. The perineal and distal genital branches could not be identified. On post-marking scans, the markers were used as identifiable structures. The location of the perineal branch, the hemorroidal branch and the dorsal nerve to penis (in male cadaver)/clitoris (in female cadaver) could be seen. However, the visualization of these branches was suboptimal. The contralateral corresponding nerves were poorly seen despite marking on the surgical side. The nerve was best seen on axial T1W and T2W SPAIR images. The proximal segment could be seen well on 3D DW PSIF sequence. T2W SPACE was not very useful in visualization of this small nerve or its branches. CONCLUSION: Proximal pudendal nerve is easily seen on MR neurography, however it is not possible to identify distal branches of the pudendal nerve even after surgical marking. PMID- 27551341 TI - Free-breathing radial volumetric interpolated breath-hold examination vs breath hold cartesian volumetric interpolated breath-hold examination magnetic resonance imaging of the liver at 1.5T. AB - AIM: To compare breath-hold cartesian volumetric interpolated breath-hold examination (cVIBE) and free-breathing radial VIBE (rVIBE) and determine whether rVIBE could replace cVIBE in routine liver magnetic resonance imaging (MRI). METHODS: In this prospective study, 15 consecutive patients scheduled for routine MRI of the abdomen underwent pre- and post-contrast breath-hold cVIBE imaging (19 s acquisition time) and free-breathing rVIBE imaging (111 s acquisition time) on a 1.5T Siemens scanner. Three radiologists with 2, 4, and 8 years post-fellowship experience in abdominal imaging evaluated all images. The radiologists were blinded to the sequence types, which were presented in a random order for each patient. For each sequence, the radiologists scored the cVIBE and rVIBE images for liver edge sharpness, hepatic vessel clarity, presence of artifacts, lesion conspicuity, fat saturation, and overall image quality using a five-point scale. RESULTS: Compared to rVIBE, cVIBE yielded significantly (P < 0.001) higher scores for liver edge sharpness (mean score, 3.87 vs 3.37), hepatic-vessel clarity (3.71 vs 3.18), artifacts (3.74 vs 3.06), lesion conspicuity (3.81 vs 3.2), and overall image quality (3.91 vs 3.24). cVIBE and rVIBE did not significantly differ in quality of fat saturation (4.12 vs 4.03, P = 0.17). The inter-observer variability with respect to differences between rVIBE and cVIBE scores was close to zero compared to random error and inter-patient variation. Quality of rVIBE images was rated as acceptable for all parameters. CONCLUSION: rVIBE cannot replace cVIBE in routine liver MRI. At 1.5T, free-breathing rVIBE yields acceptable, although slightly inferior image quality compared to breath-hold cVIBE. PMID- 27551342 TI - Cone beam computed tomography aided diagnosis and treatment of endodontic cases: Critical analysis. AB - Although intraoral radiographs still remain the imaging method of choice for the evaluation of endodontic patients, in recent years, the utilization of cone beam computed tomography (CBCT) in endodontics showed a significant jump. This case series presentation shows the importance of CBCT aided diagnosis and treatment of complex endodontic cases such as; root resorption, missed extra canal, fusion, oblique root fracture, non-diagnosed periapical pathology and horizontal root fracture. CBCT may be a useful diagnostic method in several endodontic cases where intraoral radiography and clinical examination alone are unable to provide sufficient information. PMID- 27551343 TI - Differential repetitive DNA composition in the centromeric region of chromosomes of Amazonian lizard species in the family Teiidae. AB - Differences in heterochromatin distribution patterns and its composition were observed in Amazonian teiid species. Studies have shown repetitive DNA harbors heterochromatic blocks which are located in centromeric and telomeric regions in Ameiva ameiva (Linnaeus, 1758), Kentropyx calcarata (Spix, 1825), Kentropyx pelviceps (Cope, 1868), and Tupinambis teguixin (Linnaeus, 1758). In Cnemidophorus sp.1, repetitive DNA has multiple signals along all chromosomes. The aim of this study was to characterize moderately and highly repetitive DNA sequences by C ot1-DNA from Ameiva ameiva and Cnemidophorus sp.1 genomes through cloning and DNA sequencing, as well as mapping them chromosomally to better understand its organization and genome dynamics. The results of sequencing of DNA libraries obtained by C ot1-DNA showed that different microsatellites, transposons, retrotransposons, and some gene families also comprise the fraction of repetitive DNA in the teiid species. FISH using C ot1-DNA probes isolated from both Ameiva ameiva and Cnemidophorus sp.1 showed these sequences mainly located in heterochromatic centromeric, and telomeric regions in Ameiva ameiva, Kentropyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin chromosomes, indicating they play structural and functional roles in the genome of these species. In Cnemidophorus sp.1, C ot1-DNA probe isolated from Ameiva ameiva had multiple interstitial signals on chromosomes, whereas mapping of C ot1-DNA isolated from the Ameiva ameiva and Cnemidophorus sp.1 highlighted centromeric regions of some chromosomes. Thus, the data obtained showed that many repetitive DNA classes are part of the genome of Ameiva ameiva, Cnemidophorus sp.1, Kentroyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin, and these sequences are shared among the analyzed teiid species, but they were not always allocated at the same chromosome position. PMID- 27551344 TI - Organization of some repetitive DNAs and B chromosomes in the grasshopper Eumastusia koebelei koebelei (Rehn, 1909) (Orthoptera, Acrididae, Leptysminae). AB - B chromosomes occur in approximately 15% of eukaryotes and are usually heterochromatic and rich in repetitive DNAs. Here we describe characteristics of a B chromosome in the grasshopper Eumastusia koebelei koebelei (Rehn, 1909) through classical cytogenetic methods and mapping of some repetitive DNAs, including multigene families, telomeric repeats and a DNA fraction enriched with repetitive DNAs obtained from DOP-PCR. Eumastusia koebelei koebelei presented 2n=23, X0 and, in one individual, two copies of the same variant of a B chromosome were noticed, which are associated during meiosis. The C-positive blocks were located in the pericentromeric regions of the standard complement and along the entire length of the B chromosomes. Some G+C-rich heterochromatic blocks were noticed, including conspicuous blocks in the B chromosomes. The mapping of 18S rDNA and U2 snDNA revealed only autosomal clusters, and the telomeric probe hybridized in terminal regions. Finally, the DOP-PCR probe obtained from an individual without a B chromosome revealed signals in the heterochromatic regions, including the entire length of the B chromosome. The possible intraspecific origin of the B chromosomes, due to the shared pool of repetitive DNAs between the A and B chromosomes and the possible consequences of their association are discussed. PMID- 27551345 TI - Cytogenetic data on six leafcutter ants of the genus Acromyrmex Mayr, 1865 (Hymenoptera, Formicidae, Myrmicinae): insights into chromosome evolution and taxonomic implications. AB - Cytogenetic data for the genus Acromyrmex Mayr, 1865 are available, to date, for a few species from Brazil and Uruguay, which have uniform chromosome numbers (2n = 38). The recent cytogenetic data of Acromyrmex striatus (Roger, 1863), including its banding patterns, showed a distinct karyotype (2n = 22), similar to earlier studied Atta Fabricius, 1804 species. Karyological data are still scarce for the leafcutter ants and many gaps are still present for a proper understanding of this group. Therefore, this study aimed at increasing cytogenetic knowledge of the genus through the characterization of other six species: Acromyrmex balzani (Emery, 1890), Acromyrmex coronatus Fabricius, 1804, Acromyrmex disciger (Mayr, 1887), Acromyrmex echinatior (Forel, 1899), Acromyrmex niger (Smith, 1858) and Acromyrmex rugosus (Smith, 1858), all of which were collected in Minas Gerais - Brazil, except for Acromyrmex echinatior which was collected in Barro Colorado - Panama. The number and morphology of the chromosomes were studied and the following banding techniques were applied: C banding, fluorochromes CMA3 and DAPI, as well as the detection of 45S rDNA using FISH technique. All the six species had the same chromosome number observed for already studied species, i.e. 2n = 38. Acromyrmex balzani had a different karyotype compared with other species mainly due to the first metacentric pair. The heterochromatin distribution also showed interspecific variation. Nevertheless, all the studied species had a pair of bands in the short arm of the first subtelocentric pair. The fluorochrome CMA3 visualized bands in the short arm of the first subtelocentric pair for all the six species, while Acromyrmex rugosus and Acromyrmex niger also demonstrated in the other chromosomes. The AT rich regions with differential staining using DAPI were not observed. 45S ribosomal genes were identified by FISH in the short arm of the first subtelocentric pair in Acromyrmex coronatus, Acromyrmex disciger and Acromyrmex niger. The uniform chromosome number in the genus Acromyrmex (2n = 38) suggests that Acromyrmex striatus (2n = 22) should be transferred to a new genus. Other aspects of the chromosome evolution in ants are also discussed. PMID- 27551346 TI - ZZ/ZW sex chromosome system in the endangered fish Lignobrycon myersi Miranda Ribeiro, 1956 (Teleostei, Characiformes, Triportheidae). AB - Lignobrycon myersi is an endemic fish species from a few coastal rivers in northeastern Brazil. Based on molecular evidence, Lignobrycon myersi and genera Triportheus Cope, 1872, Agoniates Muller & Troschel, 1845, Clupeacharax Pearson, 1924 and Engraulisoma Castro, 1981 were placed in the family Triportheidae. In the present work, we report the first cytogenetic data for Lignobrycon myersi to test the hypothesis that Lignobrycon and Triportheus are closely related. Studied specimens presented 2n=52 with 28 metacentric (m), 18 submetacentric (sm) and six subtelocentric (st) chromosomes for males and 27 m, 19 sm and 6 st for females, characterizing a ZZ/ZW sex chromosome system. The Z chromosome corresponds to the largest chromosome in karyotype while the W is about 50% smaller than the Z and largely heterochromatic. Terminal nucleolus organizer regions, GC-rich sites and 18S rDNA signals were detected on pair 14. However, additional 18S rDNA sites were observed in the W chromosome. The 5S rDNA was mainly detected on long arms of pair 7. The apparent synapomorphic chromosomal traits of Triportheus and Lignobrycon myersi reinforce their close phylogenetic relationship, suggesting that the ZZ/ZW chromosome system in both genera has arisen before cladogenic events. PMID- 27551347 TI - Meiotic behavior and H3K4m distribution in B chromosomes of Characidium gomesi (Characiformes, Crenuchidae). AB - Characidium gomesi Travasso, 1956 specimens from the Pardo River have up to four heterochromatic supernumerary chromosomes, derived from the sex chromosomes. To access the meiotic behavior and distribution of an active chromatin marker, males and females of Characidium gomesi with two or three B chromosomes were analyzed. Mitotic chromosomes were characterized using C-banding and FISH with B chromosome probes. Meiocytes were subjected to immunofluorescence-FISH assay using anti SYCP3, anti-H3K4m, and B chromosomes probes. Molecular homology of supernumeraries was confirmed by FISH and by its bivalent conformation in individuals with two of these chromosomes. In individuals with three Bs, these elements formed a bivalent and a univalent. Supernumerary and sex chromosomes exhibited H3K4m signals during pachytene contrasting with their heterochromatic and asynaptic nature, which suggest a more structural role than functional of this histone modification. The implications of this result are discussed in light of the homology, meiotic nuclear organization, and meiotic silencing of unsynapsed chomatin. PMID- 27551348 TI - Chromosome comparison of 17 species / sub-species of African Goliathini (Coleoptera, Scarabaeidae, Cetoniinae). AB - The mitotic karyotypes of 17 species of African Goliathini (Cetoniinae) are described using various chromosome banding techniques. All but one are composed of 20 chromosomes, mostly metacentric, forming a karyotype assumed to be close to that of the Polyphaga ancestor. The most derived karyotypes are those of Goliathus goliatus Drury, 1770, with eight pairs of acrocentrics and Chlorocana africana Drury, 1773, with only14 chromosomes. In species of the genera Cyprolais Burmeister, 1842, Megalorhina Westwood, 1847, Stephanocrates Kolbe, 1894 and Stephanorrhina Burmeister, 1842, large additions of variable heterochromatin are observed on both some particular autosomes and the X chromosome. Species of the genera Eudicella White, 1839 and Dicronorrhina Burmeister, 1842 share the same sub-metacentric X. Although each species possesses its own karyotype, it remains impossible to propose robust phylogenetic relationships on the basis of chromosome data only. PMID- 27551349 TI - Simultaneous visualization of different genomes (J, JSt and St) in a Thinopyrum intermedium * Thinopyrum ponticum synthetic hybrid (Poaceae) and in its parental species by multicolour genomic in situ hybridization (mcGISH). AB - Multicolour genomic in situ hybridization (mcGISH) using total genomic DNA probes from Thinopyrum bessarabicum (Savulescu & Rayss, 1923) A. Love, 1984 (genome J(b) or E(b), 2n = 14), and Pseudoroegneria spicata (Pursh, 1814) A. Love, 1980 (genome St, 2n = 14) was used to characterize the mitotic metaphase chromosomes of a synthetic hybrid of Thinopyrum intermedium (Host, 1805) Barkworth & D.R. Dewey, 1985 and Thinopyrum ponticum (Podpera, 1902) Z.-W. Liu et R.-C.Wang, 1993 named "Agropyron glael" and produced by N.V. Tsitsin in the former Soviet Union. The mcGISH pattern of this synthetic hybrid was compared to its parental wheatgrass species. Hexaploid Thinopyrum intermedium contained 19 J, 9 J(St) and 14 St chromosomes. The three analysed Thinopyrum ponticum accessions had different chromosome compositions: 43 J + 27 J(St) (PI531737), 40 J + 30 J(St) (VIR-44486) and 38 J + 32 J(St) (D-3494). The synthetic hybrid carried 18 J, 28 J(St) and 8 St chromosomes, including one pair of J-St translocation and/or decreased fluorescent intensity, resulting in unique hybridization patterns. Wheat line Mv9kr1 was crossed with the Thinopyrum intermedium * Thinopyrum ponticum synthetic hybrid in Hungary in order to transfer its advantageous agronomic traits (leaf rust and yellow rust resistance) into wheat. The chromosome composition of a wheat/A.glael F1 hybrid was 21 wheat + 28 wheatgrass (11 J + 14 J(St)+ 3 S). In the present study, mcGISH involving the simultaneous use of St and J genomic DNA as probes provided information about the type of Thinopyrum chromosomes in a Thinopyrum intermedium/Thinopyrum ponticum synthetic hybrid called A. glael. PMID- 27551350 TI - Rearrangement hotspots in the sex chromosome of the Palearctic black fly Simulium bergi (Diptera, Simuliidae). AB - An extreme example of nonrandom rearrangements, especially inversion breaks, is described in the polytene chromosomes of the black fly Simulium bergi Rubtsov, 1956 from Armenia and Turkey. A total of 48 rearrangements was discovered, relative to the standard banding sequence for the subgenus Simulium Latreille, 1802. One rearrangement, an inversion (IIS-C) in the short arm of the second chromosome, was fixed. Six (12.5%) of the rearrangements were autosomal polymorphisms, and the remaining 41 (85.4%) were sex linked. More than 40 X- and Y-linked rearrangements, predominantly inversions, were clustered in the long arm of the second chromosome (IIL), representing about 15% of the total complement. The pattern conforms to a nonrandom model of chromosome breakage, perhaps associated with an underlying molecular mechanism. PMID- 27551351 TI - Chromosomal analysis of Physalaemus kroyeri and Physalaemus cicada (Anura, Leptodactylidae). AB - All the species of Physalaemus Fitzinger, 1826 karyotyped up until now have been classified as 2n = 22. The species of the Physalaemus cuvieri group analyzed by C banding present a block of heterochromatin in the interstitial region of the short arm of pair 5. Physalaemus cicada Bokermann, 1966 has been considered to be a member of the Physalaemus cuvieri species group, although its interspecific phylogenetic relationships remain unknown. The PcP190 satellite DNA has been mapped on the chromosomes of most of the species of the Physalaemus cuvieri group. For two species, Physalaemus cicada and Physalaemus kroyeri (Reinhardt & Lutken, 1862), however, only the chromosome number and morphology are known. Given this, the objective of the present study was to analyze the chromosomes of Physalaemus cicada and Physalaemus kroyeri, primarily by C-banding and PcP190 mapping. The results indicate that Physalaemus kroyeri and Physalaemus cicada have similar karyotypes, which were typical of Physalaemus. In both species, the NORs are located on the long arm of pair 8, and the C-banding indicated that, among other features, Physalaemus kroyeri has the interstitial band on chromosome 5, which is however absent in Physalaemus cicada. Even so, a number of telomeric bands were observed in Physalaemus cicada. The mapping of the PcP190 satellite DNA highlighted areas of the centromeric region of the chromosomes of pair 1 in both species, although in Physalaemus kroyeri, heteromorphism was also observed in pair 3. The cytogenetic evidence does not support the inclusion of Physalaemus cicada in the Physalaemus cuvieri group. In the case of Physalaemus kroyeri, the interstitial band on pair 5 is consistent with the existence of a cytogenetic synapomorphy in the Physalaemus cuvieri species group. PMID- 27551352 TI - The Interlanguage Speech Intelligibility Benefit as Bias Toward Native-Language Phonology. AB - Two hypotheses have been advanced in the recent literature with respect to the so called Interlanguage Speech Intelligibility Benefit (ISIB): a nonnative speaker will be better understood by a another nonnative listener than a native speaker of the target language will be (a) only when the nonnatives share the same native language (matched interlanguage) or (b) even when the nonnatives have different mother tongues (non-matched interlanguage). Based on a survey of published experimental materials, the present article will demonstrate that both the restricted (a) and the generalized (b) hypotheses are false when the ISIB effect is evaluated in terms of absolute intelligibility scores. We will then propose a simple way to compute a relative measure for the ISIB (R-ISIB), which we claim is a more insightful way of evaluating the interlanguage benefit, and test the hypotheses in relative (R-ISIB) terms on the same literature data. We then find that our R-ISIB measure only supports the more restricted hypothesis (a) while rejecting the more general hypothesis (b). This finding shows that the native language shared by the interactants biases the listener toward interpreting sounds in terms of the phonology of the shared mother tongue. PMID- 27551353 TI - Model Fitting Versus Curve Fitting: A Model of Renormalization Provides a Better Account of Age Aftereffects Than a Model of Local Repulsion. AB - Recently, we proposed that the aftereffects of adapting to facial age are consistent with a renormalization of the perceived age (e.g., so that after adapting to a younger or older age, all ages appear slightly older or younger, respectively). This conclusion has been challenged by arguing that the aftereffects can also be accounted for by an alternative model based on repulsion (in which facial ages above or below the adapting age are biased away from the adaptor). However, we show here that this challenge was based on allowing the fitted functions to take on values which are implausible and incompatible across the different adapting conditions. When the fits are constrained or interpreted in terms of standard assumptions about normalization and repulsion, then the two analyses both agree in pointing to a pattern of renormalization in age aftereffects. PMID- 27551354 TI - Peripheral Color Demo. AB - A set of structured demonstrations of the vividness of peripheral color vision is provided by arrays of multicolored disks scaled with eccentricity. These demonstrations are designed to correct the widespread misconception that peripheral color vision is weak or nonexistent. PMID- 27551356 TI - Perception of Solar Eclipses Captured by Art Explains How Imaging Misrepresented the Source of the Solar Wind. AB - The visible corona revealed by the natural phenomenon of solar eclipses has been studied for 150 years. A turning point has been the discovery that the true spatial distribution of coronal brightness can neither be seen nor imaged on account of its unprecedented dynamic range. Howard Russell Butler (1856-1934), the painter of solar eclipses in the early 20th century, possessed the extraordinary skill of painting from memory what he saw for only a brief time. His remarkable but forgotten eclipse paintings are, therefore, ideal for capturing and representing best the perceptual experience of the visible corona. Explained here is how by bridging the eras of visual (late 19th century) and imaging investigations (since the latter half of the 20th century), Butler's paintings reveal why white-light images misled researching and understanding the Sun's atmosphere, the solar wind. The closure in understanding solar eclipses through the convergence of perception, art, imaging, science and the history of science promises to enrich the experience of viewing and photographing the first solar eclipse of the 21st century in the United States on 21st August 2017. PMID- 27551355 TI - Intensive Foreign Language Learning Reveals Effects on Categorical Perception of Sibilant Voicing After Only 3 Weeks. AB - Models of speech learning suggest that adaptations to foreign language sound categories take place within 6 to 12 months of exposure to a foreign language. Results from laboratory language training show effects of very targeted training on nonnative speech contrasts within only 1 to 4 weeks of training. Results from immersion studies are inconclusive, but some suggest continued effects on nonnative speech perception after 6 to 8 years of experience. We investigated this apparent discrepancy in the timing of adaptation to foreign speech sounds in a longitudinal study of foreign language learning. We examined two groups of Danish language officer cadets learning either Arabic (Modern Standard Arabic and Egyptian Arabic) or Dari (Afghan Farsi) through intensive multifaceted language training. We conducted two experiments (identification and discrimination) with the cadets who were tested four times: at the start (T0), after 3 weeks (T1), 6 months (T2), and 19 months (T3). We used a phonemic Arabic contrast (pharyngeal vs. glottal frication) and a phonemic Dari contrast (sibilant voicing) as stimuli. We observed an effect of learning on the Dari learners' identification of the Dari stimuli already after 3 weeks of language training, which was sustained, but not improved, after 6 and 19 months. The changes in the Dari learners' identification functions were positively correlated with their grades after 6 months. We observed no other learning effects at the group level. We discuss the results in the light of predictions from speech learning models. PMID- 27551357 TI - Reconsidering Visual Search. AB - The visual search paradigm has had an enormous impact in many fields. A theme running through this literature has been the distinction between preattentive and attentive processing, which I refer to as the two-stage assumption. Under this assumption, slopes of set-size and response time are used to determine whether attention is needed for a given task or not. Even though a lot of findings question this two-stage assumption, it still has enormous influence, determining decisions on whether papers are published or research funded. The results described here show that the two-stage assumption leads to very different conclusions about the operation of attention for identical search tasks based only on changes in response (presence/absence versus Go/No-go responses). Slopes are therefore an ambiguous measure of attentional involvement. Overall, the results suggest that the two-stage model cannot explain all findings on visual search, and they highlight how slopes of response time and set-size should only be used with caution. PMID- 27551358 TI - Stereoscopy Amplifies Emotions Elicited by Facial Expressions. AB - Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants' gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15 65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions. PMID- 27551359 TI - Part and Whole in Pictorial Relief. AB - What are "natural parts" of pictorial reliefs? Intuitively, and suggested by common lore from the visual arts, they are the bulges that stick out toward the observer. Each such bulge contains a (locally) nearest point and is bounded by one or (usually) more curvilinear ruts. The latter meet in "passes" or saddle points. This divides the relief into "natural districts". From a formal analysis one knows that reliefs can be divided into "hill districts" or "dale districts", these two "natural" parcellations being fully distinct. We report empirical results that strongly suggest that visual awareness is based on a partition in bulges, which are mutually only weakly connected. Such a notion immediately explains why inverted reliefs or surfaces illuminated from below appear so different as to be mutually not recognizable. PMID- 27551360 TI - Effect of Phonotactic Constraints on Second Language Speech Processing. AB - In this study, we examined whether phonotactic constraints of the first language affect speech processing by Japanese learners of English and whether their proficiency of the second language influences it. Native English speakers and second language speakers with a high level of language proficiency and those with a low level took part in a monitoring task. They were given two kinds of sound stimuli as target syllables (i.e., consonant-vowel and consonant-vowel-consonant) and were asked to detect them in lists of words that have stress on the first or second syllable (e.g., biscuit and beside). The results showed that both stress and phonotactics facilitated segmentation strategies by the three groups. The Japanese groups did not rely on either phonotactics or morae to segment the target syllables. They rather used stress to detect the target syllables in the English words, which is a different segmentation strategy from their first language. This study showed that phonotactic constraints did not interfere with second language processing by native Japanese speakers and provided evidence that second language speakers use the segmentation strategy that is used by native speakers of the target language. PMID- 27551361 TI - Visual and Auditory Components in the Perception of Asynchronous Audiovisual Speech. AB - Research on asynchronous audiovisual speech perception manipulates experimental conditions to observe their effects on synchrony judgments. Probabilistic models establish a link between the sensory and decisional processes underlying such judgments and the observed data, via interpretable parameters that allow testing hypotheses and making inferences about how experimental manipulations affect such processes. Two models of this type have recently been proposed, one based on independent channels and the other using a Bayesian approach. Both models are fitted here to a common data set, with a subsequent analysis of the interpretation they provide about how experimental manipulations affected the processes underlying perceived synchrony. The data consist of synchrony judgments as a function of audiovisual offset in a speech stimulus, under four within subjects manipulations of the quality of the visual component. The Bayesian model could not accommodate asymmetric data, was rejected by goodness-of-fit statistics for 8/16 observers, and was found to be nonidentifiable, which renders uninterpretable parameter estimates. The independent-channels model captured asymmetric data, was rejected for only 1/16 observers, and identified how sensory and decisional processes mediating asynchronous audiovisual speech perception are affected by manipulations that only alter the quality of the visual component of the speech signal. PMID- 27551362 TI - The Perception of Cooperativeness Without Any Visual or Auditory Communication. AB - Perceiving social information such as the cooperativeness of another person is an important part of human interaction. But can people perceive the cooperativeness of others even without any visual or auditory information? In a novel experimental setup, we connected two people with a rope and made them accomplish a point-collecting task together while they could not see or hear each other. We observed a consistently emerging turn-taking behavior in the interactions and installed a confederate in a subsequent experiment who either minimized or maximized this behavior. Participants experienced this only through the haptic force-feedback of the rope and made evaluations about the confederate after each interaction. We found that perception of cooperativeness was significantly affected only by the manipulation of this turn-taking behavior. Gender- and size related judgments also significantly differed. Our results suggest that people can perceive social information such as the cooperativeness of other people even in situations where possibilities for communication are minimal. PMID- 27551363 TI - Saccades Follow Perception When Judging Location. AB - An unresolved question in vision research is whether perceptual decision making and action are based on the same or on different neural representations. Here, we address this question for a straightforward task, the judgment of location. In our experiment, observers decided on the closer of two peripheral objects situated on the horizontal meridian in opposite hemifields-and made a saccade to indicate their choice. Correct saccades landed close to the actual (physical) location of the target. However, in case of errors, saccades went in the direction of the more distant object, yet landed on a position approximating that of the closer one. Our finding supports the notion that perception and action related decisions on object location rely on the same neural representation. PMID- 27551364 TI - Cue Combination of Conflicting Color and Luminance Edges. AB - Abrupt changes in the color or luminance of a visual image potentially indicate object boundaries. Here, we consider how these cues to the visual "edge" location are combined when they conflict. We measured the extent to which localization of a compound edge can be predicted from a simple maximum likelihood estimation model using the reliability of chromatic (L-M) and luminance signals alone. Maximum likelihood estimation accurately predicted the pattern of results across a range of contrasts. Predictions consistently overestimated the relative influence of the luminance cue; although L-M is often considered a poor cue for localization, it was used more than expected. This need not indicate that the visual system is suboptimal but that its priors about which cue is more useful are not flat. This may be because, although strong changes in chromaticity typically represent object boundaries, changes in luminance can be caused by either a boundary or a shadow. PMID- 27551365 TI - "What's Your Taste in Music?" A Comparison of the Effectiveness of Various Soundscapes in Evoking Specific Tastes. AB - We report on the results of two online experiments designed to compare different soundtracks that had been composed (by various researchers and sound designers) in order to evoke/match different basic tastes. In Experiment 1, 100 participants listened to samples from 24 soundtracks and chose the taste (sweet, sour, salty, or bitter) that best matched each sample. Overall, the sweet soundtracks most effectively evoked the taste intended by the composer (participants chose sweet 56.9% of the time for the sweet soundtracks), whereas the bitter soundtracks were the least effective (participants chose bitter 31.4% of the time for the bitter soundtracks), compared with chance (choosing any specific taste 25% of the time). In Experiment 2, 50 participants rated their emotional responses (in terms of pleasantness and arousal) to the same 24 soundtrack samples and also to imaginary sweet/sour/salty/bitter-tasting foods. Associations between soundtracks and tastes were partly mediated by pleasantness for the sweet and bitter tastes and partly by arousal for the sour tastes. These results demonstrate how emotion mediation may be an additional mechanism behind sound-taste correspondences. PMID- 27551366 TI - Second-Order Footsteps Illusions. AB - In the "footsteps illusion", light and dark squares travel at constant speed across black and white stripes. The squares appear to move faster and slower as their contrast against the stripes varies. We now demonstrate some second-order footsteps illusions, in which all edges are defined by colors or textures-even though luminance-based neural motion detectors are blind to such edges. PMID- 27551367 TI - Fat Face Illusion, or Jastrow Illusion with Faces, in Humans but not in Chimpanzees. AB - When two identical faces are aligned vertically, humans readily perceive the face at the bottom to be fatter than the top one. This phenomenon is called the fat face illusion. Furthermore, an apparent similarity has been pointed out between the fat face illusion and the Jastrow illusion. Recent studies have suggested the importance of facial contours and the role of basic-level processing of faces. In the present study, we directly compared the typical Jastrow illusion and fat face illusion in humans and chimpanzees using the same task. Both humans and chimpanzees clearly showed the Jastrow illusion, but only humans perceived the face at the bottom as fatter than the top. Although further examination is necessary, these results might reflect different processing levels of faces between the two species. PMID- 27551368 TI - p38alpha MAPK disables KMT1A-mediated repression of myogenic differentiation program. AB - BACKGROUND: Master transcription factor MyoD can initiate the entire myogenic gene expression program which differentiates proliferating myoblasts into multinucleated myotubes. We previously demonstrated that histone methyltransferase KMT1A associates with and inhibits MyoD in proliferating myoblasts, and must be removed to allow differentiation to proceed. It is known that pro-myogenic signaling pathways such as PI3K/AKT and p38alpha MAPK play critical roles in enforcing associations between MyoD and transcriptional activators, while removing repressors. However, the mechanism which displaces KMT1A from MyoD, and the signals responsible, remain unknown. METHODS: To investigate the role of p38alpha on MyoD-mediated differentiation, we utilized C2C12 myoblast cells as an in vitro model. p38alpha activity was either augmented via overexpression of a constitutively active upstream kinase or blocked via lentiviral delivery of a specific p38alpha shRNA or treatment with p38alpha/beta inhibitor SB203580. Overexpression of KMT1A in these cells via lentiviral delivery was also used as a system wherein terminal differentiation is impeded by high levels of KMT1A. RESULTS: The association of KMT1A and MyoD persisted, and differentiation was blocked in C2C12 myoblasts specifically after pharmacologic or genetic blockade of p38alpha. Conversely, forced activation of p38alpha was sufficient to activate MyoD and overcome the differentiation blockade in KMT1A overexpressing C2C12 cells. Consistent with this finding, KMT1A phosphorylation during C2C12 differentiation correlated strongly with the activation of p38alpha. This phosphorylation was prevented by the inhibition of p38alpha. Biochemical studies further revealed that KMT1A can be a direct substrate for p38alpha. Importantly, chromatin immunoprecipitation (ChIP) studies show that the removal of KMT1A-mediated transcription repressive histone tri-methylation (H3K9me3) from the promoter of the Myogenin gene, a critical regulator of muscle differentiation, is dependent on p38alpha activity in C2C12 cells. Elevated p38alpha activity was also sufficient to remove this repressive H3K9me3 mark. Moreover, ChIP studies from C2C12 cells show that p38alpha activity is necessary and sufficient to establish active H3K9 acetylation on the Myogenin promoter. CONCLUSIONS: Activation of p38alpha displaces KMT1A from MyoD to initiate myogenic gene expression upon induction of myoblasts differentiation. PMID- 27551370 TI - Temporal variation in selection on male and female traits in wild tree crickets. AB - Understanding temporal variation in selection in natural populations is necessary to accurately estimate rates of divergence and macroevolutionary processes. Temporal variation in the strength and direction of selection on sex-specific traits can also explain stasis in male and female phenotype and sexual dimorphism. I investigated changes in strength and form of viability selection (via predation by wasps) in a natural population of male and female tree crickets over 4 years. I found that although the source of viability stayed the same, viability selection affected males and females differently, and the strength, direction and form of selection varied considerably from year to year. In general, males experienced significant linear selection and significant selection differentials more frequently than females, and different male traits experienced significant linear selection each year. This yearly variation resulted in overall weak but significant convex selection on a composite male trait that mostly represented leg size and wing width. Significant selection on female phenotype was uncommon, but when it was detected, it was invariably nonlinear. Significant concave selection on traits representing female body size was observed in some years, as the largest and smallest females were preyed on less (the largest may have been too heavy for flying wasps to carry). Viability selection was significantly different between males and females in 2 of 4 years. Although viability selection via predation has the potential to drive phenotypic change and sexual dimorphism, temporal variation in selection may maintain stasis. PMID- 27551369 TI - Dmrt1 polymorphism covaries with sex-determination patterns in Rana temporaria. AB - Patterns of sex-chromosome differentiation and gonadal development have been shown to vary among populations of Rana temporaria along a latitudinal transect in Sweden. Frogs from the northern-boreal population of Ammarnas displayed well differentiated X and Y haplotypes, early gonadal differentiation, and a perfect match between phenotypic and genotypic sex. In contrast, no differentiated Y haplotypes could be detected in the southern population of Tvedora, where juveniles furthermore showed delayed gonadal differentiation. Here, we show that Dmrt1, a gene that plays a key role in sex determination and sexual development across all metazoans, displays significant sex differentiation in Tvedora, with a Y-specific haplotype distinct from Ammarnas. The differential segment is not only much shorter in Tvedora than in Ammarnas, it is also less differentiated and associates with both delayed gonadal differentiation and imperfect match between phenotypic and genotypic sex. Whereas Tvedora juveniles with a local Y haplotype tend to ultimately develop as males, those without it may nevertheless become functional XX males, but with strongly female-biased progeny. Our findings suggest that the variance in patterns of sex determination documented in common frogs might result from a genetic polymorphism within a small genomic region that contains Dmrt1. They also substantiate the view that recurrent convergences of sex determination toward a limited set of chromosome pairs may result from the co option of small genomic regions that harbor key genes from the sex-determination pathway. PMID- 27551372 TI - Whitebark pine facilitation at treeline: potential interactions for disruption by an invasive pathogen. AB - In stressful environments, facilitation often aids plant establishment, but invasive plant pathogens may potentially disrupt these interactions. In many treeline communities in the northern Rocky Mountains of the U.S. and Canada, Pinus albicaulis, a stress-tolerant pine, initiates tree islands at higher frequencies than other conifers - that is, leads to leeward tree establishment more frequently. The facilitation provided by a solitary (isolated) P. albicaulis leading to tree island initiation may be important for different life-history stages for leeward conifers, but it is not known which life-history stages are influenced and protection provided. However, P. albicaulis mortality from the non native pathogen Cronartium ribicola potentially disrupts these facilitative interactions, reducing tree island initiation. In two Rocky Mountain eastern slope study areas, we experimentally examined fundamental plant-plant interactions which might facilitate tree island formation: the protection offered by P. albicaulis to leeward seed and seedling life-history stages, and to leeward krummholz conifers. In the latter case, we simulated mortality from C. ribicola for windward P. albicaulis to determine whether loss of P. albicaulis from C. ribicola impacts leeward conifers. Relative to other common solitary conifers at treeline, solitary P. albicaulis had higher abundance. More seeds germinated in leeward rock microsites than in conifer or exposed microsites, but the odds of cotyledon seedling survival during the growing season were highest in P. albicaulis microsites. Planted seedling survival was low among all microsites examined. Simulating death of windward P. albicaulis by C. ribicola reduced shoot growth of leeward trees. Loss of P. albicaulis to exotic disease may limit facilitation interactions and conifer community development at treeline and potentially impede upward movement as climate warms. PMID- 27551371 TI - Variation of life-history traits of the Asian corn borer, Ostrinia furnacalis in relation to temperature and geographical latitude. AB - Life-history traits from four geographical populations (tropical Ledong population [LD], subtropical Guangzhou [GZ] and Yongxiu populations, and temperate Langfang population [LF]) of the Asian corn borer, Ostrinia furnacalis were investigated at a wide range of temperatures (20-32 degrees C). The larval and pupal times were significantly decreased with increasing rearing temperature, and growth rate was positively correlated with temperature. The relationship between body weight and rearing temperature in O. furnacalis did not follow the temperature-size rule (TSR); all populations exhibited the highest pupal and adult weights at high temperatures or intermediate temperatures. However, development time, growth rate, and body weight did not show a constant latitudinal gradient. Across all populations at each temperature, female were significantly bigger than males, showing a female-biased sexual size dimorphism (SSD). Contrary to Rensch's rule, the SSD tended to increase with rising temperature. The subtropical GZ population exhibited the largest degree of dimorphism while the temperate LF exhibited the smallest. Male pupae lose significantly more weight at metamorphosis compared to females. The proportionate weight losses of different populations were significantly different. Adult longevity was significantly decreased with increasing temperature. Between sexes, all populations exhibit a rather female-biased adult longevity. Finally, we discuss the adaptive significance of higher temperature-inducing high body weight in the moth's life history and why the moth exhibits the reverse TSR. PMID- 27551373 TI - Leaf litter arthropod responses to tropical forest restoration. AB - Soil and litter arthropods represent a large proportion of tropical biodiversity and perform important ecosystem functions, but little is known about the efficacy of different tropical forest restoration strategies in facilitating their recovery in degraded habitats. We sampled arthropods in four 7- to 8-year-old restoration treatments and in nearby reference forests. Sampling was conducted during the wet and dry seasons using extractions from litter and pitfall samples. Restoration treatments were replicated in 50 * 50-m plots in four former pasture sites in southern Costa Rica: plantation - trees planted throughout the plot; applied nucleation/islands - trees planted in patches of different sizes; and natural regeneration - no tree planting. Arthropod abundance, measures of richness and diversity, and a number of functional groups were greater in the island treatment than in natural regeneration or plantation treatments and, in many cases, were similar to reference forest. Litter and pitfall morphospecies and functional group composition in all three restoration treatments were significantly different than reference sites, but island and plantation treatments showed more recovery than natural regeneration. Abundance and functional group diversity showed a much greater degree of recovery than community composition. Synthesis and applications: The less resource-intensive restoration strategy of planting tree islands was more effective than tree plantations in restoring arthropod abundance, richness, and functional diversity. None of the restoration strategies, however, resulted in similar community composition as reference forest after 8 years of recovery, highlighting the slow rate of recovery of arthropod communities after disturbance, and underscoring the importance of conservation of remnant forests in fragmented landscapes. PMID- 27551374 TI - Specialist pollinators deplete pollen in the spring ephemeral wildflower Claytonia virginica. AB - Pollinators that collect pollen - and specifically, pollen-specialist bees - are often considered to be the best pollinators of a (host) plant. Although pollen collectors and pollen specialists often benefit host plants, especially in the pollen that they deliver (their pollination "effectiveness"), they can also exact substantial costs because they are motivated to collect as much pollen as possible, reducing the proportion of pollen removed that is subsequently delivered to stigmas (their pollination "efficiency"). From the plant perspective, pollen grains that do not pollinate conspecific stigmas are "wasted", and potentially costly. We measured costs and benefits of nectar collecting, pollen-collecting, and pollen-specialist pollinator visitation to the spring ephemeral Claytonia virginica. Visits by the pollen-specialist bee Andrena erigeniae depleted pollen quickly and thoroughly. Although all pollinators delivered roughly the same number of grains, the pollen specialist contributed most to C. virginica pollen delivery because of high visitation rates. However, the pollen specialist also removed a large number of grains; this removal may be especially costly because it resulted in the depletion of pollen grains in C. virginica populations. While C. virginica appears to rely on pollen transfer by the pollen specialist in these populations, nectar-collecting visitors could provide the same benefit at a lower cost if their visitation rates increased. Pollen depletion affects a pollinator's value to plants, but is frequently overlooked. If they lower the effectiveness of future floral visitors, visits by A. erigeniae females to C. virginica may be more detrimental than beneficial compared to other pollinators and may, in some circumstances, reduce plant fitness rather than increase it. Therefore, A. erigeniae and C. virginica may vary in their degree of mutualism depending on the ecological context. PMID- 27551375 TI - Forest edges have high conservation value for bird communities in mosaic landscapes. AB - A major conservation challenge in mosaic landscapes is to understand how trait specific responses to habitat edges affect bird communities, including potential cascading effects on bird functions providing ecosystem services to forests, such as pest control. Here, we examined how bird species richness, abundance and community composition varied from interior forest habitats and their edges into adjacent open habitats, within a multi-regional sampling scheme. We further analyzed variations in Conservation Value Index (CVI), Community Specialization Index (CSI) and functional traits across the forest-edge-open habitat gradient. Bird species richness, total abundance and CVI were significantly higher at forest edges while CSI peaked at interior open habitats, i.e., furthest from forest edge. In addition, there were important variations in trait- and species specific responses to forest edges among bird communities. Positive responses to forest edges were found for several forest bird species with unfavorable conservation status. These species were in general insectivores, understorey gleaners, cavity nesters and long-distance migrants, all traits that displayed higher abundance at forest edges than in forest interiors or adjacent open habitats. Furthermore, consistently with predictions, negative edge effects were recorded in some forest specialist birds and in most open-habitat birds, showing increasing densities from edges to interior habitats. We thus suggest that increasing landscape-scale habitat complexity would be beneficial to declining species living in mosaic landscapes combining small woodlands and open habitats. Edge effects between forests and adjacent open habitats may also favor bird functional guilds providing valuable ecosystem services to forests in longstanding fragmented landscapes. PMID- 27551376 TI - North African hybrid sparrows (Passer domesticus, P. hispaniolensis) back from oblivion - ecological segregation and asymmetric mitochondrial introgression between parental species. AB - A stabilized hybrid form of the house sparrow (Passer domesticus) and the Spanish sparrow (P. hispaniolensis) is known as Passer italiae from the Italian Peninsula and a few Mediterranean islands. The growing attention for the Italian hybrid sparrow and increasing knowledge on its biology and genetic constitution greatly contrast the complete lack of knowledge of the long-known phenotypical hybrid sparrow populations from North Africa. Our study provides new data on the breeding biology and variation of mitochondrial DNA in three Algerian populations of house sparrows, Spanish sparrows, and phenotypical hybrids. In two field seasons, the two species occupied different breeding habitats: Spanish sparrows were only found in rural areas outside the cities and bred in open-cup nests built in large jujube bushes. In contrast, house sparrows bred only in the town centers and occupied nesting holes in walls of buildings. Phenotypical hybrids were always associated with house sparrow populations. House sparrows and phenotypical hybrids started breeding mid of March, and most pairs had three successive clutches, whereas Spanish sparrows started breeding almost one month later and had only two successive clutches. Mitochondrial introgression is strongly asymmetric because about 75% of the rural Spanish sparrow population carried house sparrow haplotypes. In contrast, populations of the Italian hybrid form, P. italiae, were genetically least diverse among all study populations and showed a near-fixation of house sparrow haplotypes that elsewhere were extremely rare or that were even unique for the Italian Peninsula. Such differences between mitochondrial gene pools of Italian and North African hybrid sparrow populations provide first evidence that different demographic histories have shaped the extant genetic diversity observed on both continents. PMID- 27551377 TI - Sex determination, longevity, and the birth and death of reptilian species. AB - Vertebrate sex-determining mechanisms (SDMs) are triggered by the genotype (GSD), by temperature (TSD), or occasionally, by both. The causes and consequences of SDM diversity remain enigmatic. Theory predicts SDM effects on species diversification, and life-span effects on SDM evolutionary turnover. Yet, evidence is conflicting in clades with labile SDMs, such as reptiles. Here, we investigate whether SDM is associated with diversification in turtles and lizards, and whether alterative factors, such as lifespan's effect on transition rates, could explain the relative prevalence of SDMs in turtles and lizards (including and excluding snakes). We assembled a comprehensive dataset of SDM states for squamates and turtles and leveraged large phylogenies for these two groups. We found no evidence that SDMs affect turtle, squamate, or lizard diversification. However, SDM transition rates differ between groups. In lizards TSD-to-GSD surpass GSD-to-TSD transitions, explaining the predominance of GSD lizards in nature. SDM transitions are fewer in turtles and the rates are similar to each other (TSD-to-GSD equals GSD-to-TSD), which, coupled with TSD ancestry, could explain TSD's predominance in turtles. These contrasting patterns can be explained by differences in life history. Namely, our data support the notion that in general, shorter lizard lifespan renders TSD detrimental favoring GSD evolution in squamates, whereas turtle longevity permits TSD retention. Thus, based on the macro-evolutionary evidence we uncovered, we hypothesize that turtles and lizards followed different evolutionary trajectories with respect to SDM, likely mediated by differences in lifespan. Combined, our findings revealed a complex evolutionary interplay between SDMs and life histories that warrants further research that should make use of expanded datasets on unexamined taxa to enable more conclusive analyses. PMID- 27551378 TI - Genetic reconstruction of a bullfrog invasion to elucidate vectors of introduction and secondary spread. AB - Reconstructing historical colonization pathways of an invasive species is critical for uncovering factors that determine invasion success and for designing management strategies. The American bullfrog (Lithobates catesbeianus) is endemic to eastern North America, but now has a global distribution and is considered to be one of the worst invaders in the world. In Montana, several introduced populations have been reported, but little is known of their sources and vectors of introduction and secondary spread. We evaluated the genetic composition of introduced populations at local (Yellowstone River floodplain) and regional (Montana and Wyoming) scales in contrast to native range populations. Our objectives were to (1) estimate the number of introductions, (2) identify probable native sources, (3) evaluate genetic variation relative to sources, and (4) characterize properties of local- and regional-scale spread. We sequenced 937 bp of the mitochondrial cytochrome b locus in 395 tadpoles collected along 100 km of the Yellowstone River, from three additional sites in MT and a proximate site in WY. Pairwise PhiST revealed high divergence among nonnative populations, suggesting at least four independent introductions into MT from diverse sources. Three cyt b haplotypes were identical to native haplotypes distributed across the Midwest and Great Lakes regions, and AMOVA confirmed the western native region as a likely source. While haplotype (H d = 0.69) and nucleotide diversity (pi = 0.005) were low in introduced bullfrogs, the levels of diversity did not differ significantly from source populations. In the Yellowstone, two identified haplotypes implied few introduction vectors and a significant relationship between genetic and river distance was found. Evidence for multiple invasions and lack of subsequent regional spread emphasizes the importance of enforcing legislation prohibiting bullfrog importation and the need for continuing public education to prevent transport of bullfrogs in MT. More broadly, this study demonstrates how genetic approaches can reveal key properties of a biological invasion to inform management strategies. PMID- 27551379 TI - Facing environmental predictability with different sources of epigenetic variation. AB - Different sources of epigenetic changes can increase the range of phenotypic options. Environmentally induced epigenetic changes and stochastic epimutations are, respectively, associated with phenotypic plasticity and diversifying bet hedging. Their relative contribution is thus expected to reflect the capacity of a genotype to face distinct changes since these strategies are differentially selected according to environmental uncertainty. To test this hypothesis, we assessed the sources of epigenetic changes on clonal fish from predictable (lakes) or unpredictable (intermittent streams) environments. DNA methylation of clones from natural conditions revealed contrasting contribution of environmentally induced versus stochastic changes according to their origins. These differences were validated in common garden experiments. Consistent with theoretical models, distinct sources of epigenetic variation prevail according to the environmental uncertainty. However, both sources act conjointly, suggesting that plasticity and random processes are complementary strategies. This represents a rigorous approach for further exploring the capacity of organisms to respond to environmental conditions. PMID- 27551380 TI - Preference for C4 shade grasses increases hatchling performance in the butterfly, Bicyclus safitza. AB - The Miocene radiation of C4 grasses under high-temperature and low ambient CO 2 levels occurred alongside the transformation of a largely forested landscape into savanna. This inevitably changed the host plant regime of herbivores, and the simultaneous diversification of many consumer lineages, including Bicyclus butterflies in Africa, suggests that the radiations of grasses and grazers may be evolutionary linked. We examined mechanisms for this plant-herbivore interaction with the grass-feeding Bicyclus safitza in South Africa. In a controlled environment, we tested oviposition preference and hatchling performance on local grasses with C3 or C4 photosynthetic pathways that grow either in open or shaded habitats. We predicted preference for C3 plants due to a hypothesized lower processing cost and higher palatability to herbivores. In contrast, we found that females preferred C4 shade grasses rather than either C4 grasses from open habitats or C3 grasses. The oviposition preference broadly followed hatchling performance, although hatchling survival was equally good on C4 or C3 shade grasses. This finding was explained by leaf toughness; shade grasses were softer than grasses from open habitats. Field monitoring revealed a preference of adults for shaded habitats, and stable isotope analysis of field-sampled individuals confirmed their preference for C4 grasses as host plants. Our findings suggest that plant-herbivore interactions can influence the direction of selection in a grass-feeding butterfly. Based on this work, we postulate future research to test whether these interactions more generally contribute to radiations in herbivorous insects via expansions into new, unexploited ecological niches. PMID- 27551381 TI - Ecosystem size matters: the dimensionality of intralacustrine diversification in Icelandic stickleback is predicted by lake size. AB - Cases of evolutionary diversification can be characterized along a continuum from weak to strong genetic and phenotypic differentiation. Several factors may facilitate or constrain the differentiation process. Comparative analyses of replicates of the same taxon at different stages of differentiation can be useful to identify these factors. We estimated the number of distinct phenotypic groups in three-spine stickleback populations from nine lakes in Iceland and in one marine population. Using the inferred number of phenotypic groups in each lake, genetic divergence from the marine population, and physical lake and landscape variables, we tested whether ecosystem size, approximated by lake size and depth, or isolation from the ancestral marine gene pool predicts the occurrence and the extent of phenotypic and genetic diversification within lakes. We find intralacustrine phenotypic diversification to be the rule rather than the exception, occurring in all but the youngest lake population and being manifest in ecologically important phenotypic traits. Neutral genetic data further indicate nonrandom mating in four of nine studied lakes, and restricted gene flow between sympatric phenotypic groups in two. Although neither the phenotypic variation nor the number of intralacustrine phenotypic groups was associated with any of our environmental variables, the number of phenotypic traits that were differentiated was significantly positively related to lake size, and evidence for restricted gene flow between sympatric phenotypic groups was only found in the largest lakes where trait specific phenotypic differentiation was highest. PMID- 27551382 TI - High dissimilarity within a multiyear annual record of pollen assemblages from a North American tallgrass prairie. AB - Grassland vegetation varies in composition across North America and has been historically influenced by multiple biotic and abiotic drivers, including fire, herbivory, and topography. Yet, the amount of temporal and spatial variability exhibited among grassland pollen assemblages, and the influence of these biotic and abiotic drivers on pollen assemblage composition and diversity has been relatively understudied. Here, we examine 4 years of modern pollen assemblages collected from a series of 28 traps at the Konza Prairie Long-Term Ecological Research Area in the Flint Hills of Kansas, with the aim of evaluating the influence of these drivers, as well as quantifying the amount of spatial and temporal variability in the pollen signatures of the tallgrass prairie biome. We include all terrestrial pollen taxa in our analyses while calculating four summative metrics of pollen diversity and composition - beta-diversity, Shannon index, nonarboreal pollen percentage, and Ambrosia:Artemisia - and find different roles of fire, herbivory, and topography variables in relation to these pollen metrics. In addition, we find significant annual differences in the means of three of these metrics, particularly the year 2013 which experienced high precipitation relative to the other 3 years of data. To quantify spatial and temporal dissimilarity among the samples over the 4-year study, we calculate pairwise squared-chord distances (SCD). The SCD values indicate higher compositional dissimilarity across the traps (0.38 mean) among all years than within a single trap from year to year (0.31 mean), suggesting that grassland vegetation can have different pollen signatures across finely sampled space and time, and emphasizing the need for additional long-term annual monitoring of grassland pollen. PMID- 27551383 TI - Into the deep: the functionality of mesopelagic excursions by an oceanic apex predator. AB - Comprehension of ecological processes in marine animals requires information regarding dynamic vertical habitat use. While many pelagic predators primarily associate with epipelagic waters, some species routinely dive beyond the deep scattering layer. Actuation for exploiting these aphotic habitats remains largely unknown. Recent telemetry data from oceanic whitetip sharks (Carcharhinus longimanus) in the Atlantic show a strong association with warm waters (>20 degrees C) less than 200 m. Yet, individuals regularly exhibit excursions into the meso- and bathypelagic zone. In order to examine deep-diving behavior in oceanic whitetip sharks, we physically recovered 16 pop-up satellite archival tags and analyzed the high-resolution depth and temperature data. Diving behavior was evaluated in the context of plausible functional behavior hypotheses including interactive behaviors, energy conservation, thermoregulation, navigation, and foraging. Mesopelagic excursions (n = 610) occurred throughout the entire migratory circuit in all individuals, with no indication of site specificity. Six depth-versus-time descent and ascent profiles were identified. Descent profile shapes showed little association with examined environmental variables. Contrastingly, ascent profile shapes were related to environmental factors and appear to represent unique behavioral responses to abiotic conditions present at the dive apex. However, environmental conditions may not be the sole factors influencing ascents, as ascent mode may be linked to intentional behaviors. While dive functionality remains unconfirmed, our study suggests that mesopelagic excursions relate to active foraging behavior or navigation. Dive timing, prey constituents, and dive shape support foraging as the most viable hypothesis for mesopelagic excursions, indicating that the oceanic whitetip shark may regularly survey extreme environments (deep depths, low temperatures) as a foraging strategy. At the apex of these deep-water excursions, sharks exhibit a variable behavioral response, perhaps, indicating the presence or absence of prey. PMID- 27551385 TI - Feral Cat Globetrotters: genetic traces of historical human-mediated dispersal. AB - Endemic species on islands are highly susceptible to local extinction, in particular if they are exposed to invasive species. Invasive predators, such as feral cats, have been introduced to islands around the world, causing major losses in local biodiversity. In order to control and manage invasive species successfully, information about source populations and level of gene flow is essential. Here, we investigate the origin of feral cats of Hawaiian and Australian islands to verify their European ancestry and a potential pattern of isolation by distance. We analyzed the genetic structure and diversity of feral cats from eleven islands as well as samples from Malaysia and Europe using mitochondrial DNA (ND5 and ND6 regions) and microsatellite DNA data. Our results suggest an overall European origin of Hawaiian cats with no pattern of isolation by distance between Australian, Malaysian, and Hawaiian populations. Instead, we found low levels of genetic differentiation between samples from Tasman Island, Lana'i, Kaho'olawe, Cocos (Keeling) Island, and Asia. As these populations are separated by up to 10,000 kilometers, we assume an extensive passive dispersal event along global maritime trade routes in the beginning of the 19th century, connecting Australian, Asian, and Hawaiian islands. Thus, islands populations, which are characterized by low levels of current gene flow, represent valuable sources of information on historical, human-mediated global dispersal patterns of feral cats. PMID- 27551384 TI - Does asymmetric gene flow among matrilines maintain the evolutionary potential of the European eel? AB - Using evolutionary theory to predict the dynamics of populations is one of the aims of evolutionary conservation. In endangered species, with geographic range extending over continuous areas, the predictive capacity of evolutionary-based conservation measures greatly depends on the accurate identification of reproductive units. The endangered European eel (Anguilla anguilla) is a highly migratory fish species with declining population due to a steep recruitment collapse in the beginning of the 1980s. Despite punctual observations of genetic structure, the population is viewed as a single panmictic reproductive unit. To understand the possible origin of the detected structure in this species, we used a combination of mitochondrial and nuclear loci to indirectly evaluate the possible existence of cryptic demes. For that, 403 glass eels from three successive cohorts arriving at a single location were screened for phenotypic and genetic diversity, while controlling for possible geographic variation. Over the 3 years of sampling, we consistently identified three major matrilines which we hypothesized to represent demes. Interestingly, not only we found that population genetic models support the existence of those matriline-driven demes over a completely panmictic mode of reproduction, but also we found evidence for asymmetric gene flow amongst those demes. We uphold the suggestion that the detection of demes related to those matrilines reflect a fragmented spawning ground, a conceptually plausible consequence of the low abundance that the European eel has been experiencing for three decades. Furthermore, we suggest that this cryptic organization may contribute to the maintenance of the adaptive potential of the species. PMID- 27551386 TI - A shift from exploitation to interference competition with increasing density affects population and community dynamics. AB - Intraspecific competition influences population and community dynamics and occurs via two mechanisms. Exploitative competition is an indirect effect that occurs through use of a shared resource and depends on resource availability. Interference competition occurs by obstructing access to a resource and may not depend on resource availability. Our study tested whether the strength of interference competition changes with protozoa population density. We grew experimental microcosms of protozoa and bacteria under different combinations of protozoan density and basal resource availability. We then solved a dynamic predator-prey model for parameters of the functional response using population growth rates measured in our experiment. As population density increased, competition shifted from exploitation to interference, and competition was less dependent on resource levels. Surprisingly, the effect of resources was weakest when competition was the most intense. We found that at low population densities, competition was largely exploitative and resource availability had a large effect on population growth rates, but the effect of resources was much weaker at high densities. This shift in competitive mechanism could have implications for interspecific competition, trophic interactions, community diversity, and natural selection. We also tested whether this shift in the mechanism of competition with protozoa density affected the structure of the bacterial prey community. We found that both resources and protozoa density affected the structure of the bacterial prey community, suggesting that competitive mechanism may also affect trophic interactions. PMID- 27551387 TI - Incipient sympatric speciation in Midas cichlid fish from the youngest and one of the smallest crater lakes in Nicaragua due to differential use of the benthic and limnetic habitats? AB - Understanding how speciation can occur without geographic isolation remains a central objective in evolutionary biology. Generally, some form of disruptive selection and assortative mating are necessary for sympatric speciation to occur. Disruptive selection can arise from intraspecific competition for resources. If this competition leads to the differential use of habitats and variation in relevant traits is genetically determined, then assortative mating can be an automatic consequence (i.e., habitat isolation). In this study, we caught Midas cichlid fish from the limnetic (middle of the lake) and benthic (shore) habitats of Crater Lake Asososca Managua to test whether some of the necessary conditions for sympatric speciation due to intraspecific competition and habitat isolation are given. Lake As. Managua is very small (<900 m in diameter), extremely young (maximally 1245 years of age), and completely isolated. It is inhabited by, probably, only a single endemic species of Midas cichlids, Amphilophus tolteca. We found that fish from the limnetic habitat were more elongated than fish collected from the benthic habitat, as would be predicted from ecomorphological considerations. Stable isotope analyses confirmed that the former also exhibit a more limnetic lifestyle than the latter. Furthermore, split-brood design experiments in the laboratory suggest that phenotypic plasticity is unlikely to explain much of the observed differences in body elongation that we observed in the field. Yet, neutral markers (microsatellites) did not reveal any genetic clustering in the population. Interestingly, demographic inferences based on RAD seq data suggest that the apparent lack of genetic differentiation at neutral markers could simply be due to a lack of time, as intraspecific competition may only have begun a few hundred generations ago. PMID- 27551388 TI - Evidence of weaker phenotypic plasticity by prey to novel cues from non-native predators. AB - A central question in evolutionary biology is how coevolutionary history between predator and prey influences their interactions. Contemporary global change and range expansion of exotic organisms impose a great challenge for prey species, which are increasingly exposed to invading non-native predators, with which they share no evolutionary history. Here, we complete a comprehensive survey of empirical studies of coevolved and naive predator-prey interactions to assess whether a shared evolutionary history with predators influences the magnitude of predator-induced defenses mounted by prey. Using marine bivalves and gastropods as model prey, we found that coevolved prey and predator-naive prey showed large discrepancies in magnitude of predator-induced phenotypic plasticity. Although naive prey, predominantly among bivalve species, did exhibit some level of plasticity - prey exposed to native predators showed significantly larger amounts of phenotypic plasticity. We discuss these results and the implications they may have for native communities and ecosystems. PMID- 27551389 TI - Phylogeographic insights into the invasion history and secondary spread of the signal crayfish in Japan. AB - Successful invasion by nonindigenous species is often attributed to high propagule pressure, yet some foreign species become widespread despite showing reduced genetic variation due to founder effects. The signal crayfish (Pacifastacus leniusculus) is one such example, where rapid spread across Japan in recent decades is believed to be the result of only three founding populations. To infer the history and explore the success of this remarkable crayfish invasion, we combined detailed phylogeographical and morphological analyses conducted in both the introduced and native ranges. We sequenced 16S mitochondrial DNA of signal crayfish from across the introduced range in Japan (537 samples, 20 sites) and the native range in western North America (700 samples, 50 sites). Because chela size is often related to aggressive behavior in crayfish, and hence, their invasion success, we also measured chela size of a subset of specimens in both introduced and native ranges. Genetic diversity of introduced signal crayfish populations was as high as that of the dominant phylogeographic group in the native range, suggesting high propagule pressure during invasion. More recently established crayfish populations in Japan that originated through secondary spread from one of the founding populations exhibit reduced genetic diversity relative to older populations, probably as a result of founder effects. However, these newer populations also show larger chela size, consistent with expectations of rapid adaptations or phenotypic responses during the invasion process. Introduced signal crayfish populations in Japan originate from multiple source populations from a wide geographic range in the native range of western North America. A combination of high genetic diversity, especially for older populations in the invasive range, and rapid adaptation to colonization, manifested as larger chela in recent invasions, likely contribute to invasion success of signal crayfish in Japan. PMID- 27551391 TI - Detecting the small island effect and nestedness of herpetofauna of the West Indies. AB - To detect the small island effect (SIE) and nestedness patterns of herpetofauna of the West Indies, we derived and updated data on the presence/absence of herpetofauna in this region from recently published reviews. We applied regression-based analyses, including linear regression and piecewise regressions with two and three segments, to detect the SIE and then used the Akaike's information criterion (AIC) as a criterion to select the best model. We used the NODF (a nestedness metric based on overlap and decreasing fill) to quantify nestedness and employed two null models to determine significance. Moreover, a random sampling effort was made to infer about the degree of nestedness at portions of the entire community. We found piecewise regression with three segments performed best, suggesting the species-area relationships possess three different patterns that resulted from two area thresholds: a first one, delimiting the SIE, and a second one, delimiting evolutionary processes. We also found that taxa with lower resource requirement, higher dispersal ability, and stronger adaptation to the environment generally displayed lower corresponding threshold values, indicating superior taxonomic groups could earlier end the SIE period and start in situ speciation as the increase of island size. Moreover, the traditional two-segment piecewise regression method may cause poor estimations for both slope and threshold value of the SIE. Therefore, we suggest previous SIE detection works that conducted by two-segment piecewise regression method, ignoring the possibility of three segments, need to be reanalyzed. Antinestedness occurred in the entire system, whereas high degree of nestedness could still occur in portions within the region. Nestedness may still be applicable to conservation planning at portions even if it is antinested at the regional scale. However, nestedness may not be applicable to conservation planning at the regional scale even if nestedness does exist among sampling islands from a portion. PMID- 27551390 TI - A family of functional dissimilarity measures for presence and absence data. AB - Plot-to-plot dissimilarity measures are considered a valuable tool for understanding the complex ecological mechanisms that drive community composition. Traditional presence/absence coefficients are usually based on different combinations of the matching/mismatching components of the 2 * 2 contingency table. However, more recently, dissimilarity measures that incorporate information about the degree of functional differences between the species in both plots have received increasing attention. This is because such "functional dissimilarity measures" capture information on the species' functional traits, which is ignored by traditional coefficients. Therefore, functional dissimilarity measures tend to correlate more strongly with ecosystem-level processes, as species influence these processes via their traits. In this study, we introduce a new family of dissimilarity measures for presence and absence data, which consider functional dissimilarities among species in the calculation of the matching/mismatching components of the 2 * 2 contingency table. Within this family, the behavior of the Jaccard coefficient, together with its additive components, species replacement, and richness difference, is examined by graphical comparisons and ordinations based on simulated data. PMID- 27551392 TI - A goodness-of-fit test for occupancy models with correlated within-season revisits. AB - Occupancy modeling is important for exploring species distribution patterns and for conservation monitoring. Within this framework, explicit attention is given to species detection probabilities estimated from replicate surveys to sample units. A central assumption is that replicate surveys are independent Bernoulli trials, but this assumption becomes untenable when ecologists serially deploy remote cameras and acoustic recording devices over days and weeks to survey rare and elusive animals. Proposed solutions involve modifying the detection-level component of the model (e.g., first-order Markov covariate). Evaluating whether a model sufficiently accounts for correlation is imperative, but clear guidance for practitioners is lacking. Currently, an omnibus goodness-of-fit test using a chi square discrepancy measure on unique detection histories is available for occupancy models (MacKenzie and Bailey, Journal of Agricultural, Biological, and Environmental Statistics, 9, 2004, 300; hereafter, MacKenzie-Bailey test). We propose a join count summary measure adapted from spatial statistics to directly assess correlation after fitting a model. We motivate our work with a dataset of multinight bat call recordings from a pilot study for the North American Bat Monitoring Program. We found in simulations that our join count test was more reliable than the MacKenzie-Bailey test for detecting inadequacy of a model that assumed independence, particularly when serial correlation was low to moderate. A model that included a Markov-structured detection-level covariate produced unbiased occupancy estimates except in the presence of strong serial correlation and a revisit design consisting only of temporal replicates. When applied to two common bat species, our approach illustrates that sophisticated models do not guarantee adequate fit to real data, underscoring the importance of model assessment. Our join count test provides a widely applicable goodness-of-fit test and specifically evaluates occupancy model lack of fit related to correlation among detections within a sample unit. Our diagnostic tool is available for practitioners that serially deploy survey equipment as a way to achieve cost savings. PMID- 27551393 TI - Hierarchical neighbor effects on mycorrhizal community structure and function. AB - Theory predicts that neighboring communities can shape one another's composition and function, for example, through the exchange of member species. However, empirical tests of the directionality and strength of these effects are rare. We determined the effects of neighboring communities on one another through experimental manipulation of a plant-fungal model system. We first established distinct ectomycorrhizal fungal communities on Douglas-fir seedlings that were initially grown in three soil environments. We then transplanted seedlings and mycorrhizal communities in a fully factorial experiment designed to quantify the direction and strength of neighbor effects by focusing on changes in fungal community species composition and implications for seedling growth (a proxy for community function). We found that neighbor effects on the composition and function of adjacent communities follow a dominance hierarchy. Specifically, mycorrhizal communities established from soils collected in Douglas-fir plantations were both the least sensitive to neighbor effects, and exerted the strongest influence on their neighbors by driving convergence in neighbor community composition and increasing neighbor seedling vigor. These results demonstrate that asymmetric neighbor effects mediated by ecological history can determine both community composition and function. PMID- 27551394 TI - Out of the forest: past and present range expansion of a parthenogenetic weevil pest, or how to colonize the world successfully. AB - Previous research revealed complex diversification patterns in the parthenogenetic weevil Naupactus cervinus. To understand the origin of clonal diversity and successful spreading of this weevil, we investigated its geographic origin and possible dispersal routes and whether parthenogens can persist in habitats under unsuitable environmental conditions. This study is based on samples taken throughout a broad area of the species' range. We used both mitochondrial and nuclear markers and applied phylogenetic and network analyses to infer possible relationships between haplotypes. Bayesian phylogeographic analyses and ecological niche modeling were used to investigate the processes that shaped genetic diversity and enabled the colonization of new geographic areas. Southeastern Brazil emerges as the original distribution area of N. cervinus. We detected two range expansions, one along natural corridors during the Pleistocene and the other in countries outside South America during recent times. Isolation due to climate shifts during the early Pleistocene led to diversification in two divergent clades, which probably survived in different refugia of the Paranaense Forest and the Parana River delta. The origin of the clonal diversity was probably a complex process including mutational diversification, hybridization, and secondary colonization. The establishment of N. cervinus in areas outside its native range may indicate adaptation to drier and cooler conditions. Parthenogenesis would be advantageous for the colonization of new environments by preventing the breakup of successful gene combinations. As in other insect pests, the present distribution of N. cervinus results from both its evolutionary history and its recent history related to human activities. PMID- 27551395 TI - Nematode endoparasites do not codiversify with their stick insect hosts. AB - Host-parasite coevolution stems from reciprocal selection on host resistance and parasite infectivity, and can generate some of the strongest selective pressures known in nature. It is widely seen as a major driver of diversification, the most extreme case being parallel speciation in hosts and their associated parasites. Here, we report on endoparasitic nematodes, most likely members of the mermithid family, infecting different Timema stick insect species throughout California. The nematodes develop in the hemolymph of their insect host and kill it upon emergence, completely impeding host reproduction. Given the direct exposure of the endoparasites to the host's immune system in the hemolymph, and the consequences of infection on host fitness, we predicted that divergence among hosts may drive parallel divergence in the endoparasites. Our phylogenetic analyses suggested the presence of two differentiated endoparasite lineages. However, independently of whether the two lineages were considered separately or jointly, we found a complete lack of codivergence between the endoparasitic nematodes and their hosts in spite of extensive genetic variation among hosts and among parasites. Instead, there was strong isolation by distance among the endoparasitic nematodes, indicating that geography plays a more important role than host-related adaptations in driving parasite diversification in this system. The accumulating evidence for lack of codiversification between parasites and their hosts at macroevolutionary scales contrasts with the overwhelming evidence for coevolution within populations, and calls for studies linking micro- versus macroevolutionary dynamics in host-parasite interactions. PMID- 27551396 TI - Extensive variation, but not local adaptation in an Australian alpine daisy. AB - Alpine plants often occupy diverse habitats within a similar elevation range, but most research on local adaptation in these plants has focused on elevation gradients. In testing for habitat-related local adaptation, local effects on seed quality and initial plant growth should be considered in designs that encompass multiple populations and habitats. We tested for local adaptation across alpine habitats in a morphologically variable daisy species, Brachyscome decipiens, in the Bogong High Plains in Victoria, Australia. We collected seed from different habitats, controlled for maternal effects through initial seed size estimates, and characterized seedling survival and growth in a field transplant experiment. We found little evidence for local adaptation for survival or plant size, based on three adaptation measures: Home versus Away, Local versus Foreign, and Sympatric versus Allopatric (SA). The SA measure controlled for planting site and population (site-of-origin) effects. There were significant differences due to site-of-origin and planting site effects. An important confounding factor was the size of plants directly after transplantation of seedlings, which had a large impact on subsequent seedling survival and growth. Initial differences in plant width and height influenced subsequent survival across the growing season but in opposing directions: wide plants had higher survival, but tall plants had lower survival. In an additional controlled garden experiment at Cranbourne Royal Botanic Gardens, site-of-origin effects detected in the field experiments disappeared under more benign homogeneous conditions. Although B. decipiens from different source areas varied significantly when grown across a range of alpine habitats, these differences did not translate into a local or habitat-related fitness advantage. This lack of local advantage may signal weak past selection, and/or weak adaptive transgeneration (plasticity) effects. PMID- 27551397 TI - Why do ovigerous females approach courting males? Female preferences and sensory biases in a fiddler crab. AB - Perceptual biases explain the origin and evolution of female preference in many species. Some responses that mediate mate choice, however, may have never been used in nonmating contexts. In the fiddler crab, Uca mjoebergi, mate-searching females prefer faster wave rates and leading wave; however, it remains unclear whether such responses evolved in a mating context (i.e., the preference has effect on the fitness of the female and her offspring that arise from mating with a particular male) or a nonmating contexts (i.e., a female obtains direct benefits through selecting the male with a more detectable trait). Here, we compared the preferences of mate-searching with those of ovigerous females that are searching for a burrow and do not concern about male "quality." Results showed that as both mate-searching and ovigerous females preferentially approached robotic males with faster wave rates. This suggests that wave rate increases detectability/locatability of males, but the mating preference for this trait is unlikely to evolve in the mating context (although it may currently function in mate choice), as it does not provide fitness-related benefit to females or her offspring. Wave leadership, in contract, was attractive to mate searching females, but not ovigerous females, suggesting that female preference for leadership evolves because wave leadership conveys information about male quality. We provide not only an empirical evidence of sensory biases (in terms of the preference for faster wave), but the first experimental evidence that mating context can be the only selection force that mediates the evolution of male sexual traits and female preference (in terms of the preference for leading wave). PMID- 27551398 TI - Population genetic evidence for sex-specific dispersal in an inbred social spider. AB - Dispersal in most group-living species ensures gene flow among groups, but in cooperative social spiders, juvenile dispersal is suppressed and colonies are highly inbred. It has been suggested that such inbred sociality is advantageous in the short term, but likely to lead to extinction or reduced speciation rates in the long run. In this situation, very low levels of dispersal and gene flow among colonies may have unusually important impacts on fitness and persistence of social spiders. We investigated sex-specific differences in dispersal and gene flow among colonies, as reflected in the genetic structure within colonies and populations of the African social spider Stegodyphus dumicola Pocock, 1898 (Eresidae). We used DNA fingerprinting and mtDNA sequence data along with spatial mapping of colonies to compare male and female patterns of relatedness within and among colonies at three study sites. Samples were collected during and shortly after the mating season to detect sex-specific dispersal. Distribution of mtDNA haplotypes was consistent with proliferation of social nests by budding and medium- to long-distance dispersal by ballooning females. Analysis of molecular variance and spatial autocorrelation analyses of AFLPs showed high levels of genetic similarity within colonies, and STRUCTURE analyses revealed that the number of source populations contributing to colonies ranged from one to three. We also showed significant evidence of male dispersal among colonies at one site. These results support the hypothesis that in social spiders, genetic cohesion among populations is maintained by long-distance dispersal of female colony founders. Genetic diversity within colonies is maintained by colony initiation by multiple dispersing females, and adult male dispersal over short distances. Male dispersal may be particularly important in maintaining gene flow among colonies in local populations. PMID- 27551399 TI - Unexpectedly complex gradation of coral population structure in the Nansei Islands, Japan. AB - To establish effective locations and sizes of potential protected areas for reef ecosystems, detailed information about source and sink relationships between populations is critical, especially in archipelagic regions. Therefore, we assessed population structure and genetic diversity of Acropora tenuis, one of the dominant stony coral species in the Pacific, using 13 microsatellite markers to investigate 298 colonies from 15 locations across the Nansei Islands in southwestern Japan. Genetic diversity was not significant among sampling locations, even in possibly peripheral locations. In addition, our results showed that there are at least two populations of A. tenuis in the study area. The level of genetic differentiation between these populations was relatively low, but significant between many pairs of sampling locations. Directions of gene flow, which were estimated using a coalescence-based approach, suggest that gene flow not only occurs from south to north, but also from north to south in various locations. Consequently, the Yaeyama Islands and the Amami Islands are potential northern and southern sources of corals. On the other hand, the Miyako Islands and west central Okinawa Island are potential sink populations. The Kerama Islands and the vicinity of Taketomi Island are potential contact points of genetic subdivision of coral populations in the Nansei Islands. We found that genetic population structure of A. tenuis in the Nansei Islands is more complex than previously thought. These cryptic populations are very important for preserving genetic diversity and should be maintained. PMID- 27551400 TI - Reintroduction of rare arable plants by seed transfer. What are the optimal sowing rates? AB - During the past decades, agro-biodiversity has markedly declined and some species are close to extinction in large parts of Europe. Reintroduction of rare arable plant species in suitable habitats could counteract this negative trend. The study investigates optimal sowing rates of three endangered species (Legousia speculum-veneris (L.) Chaix, Consolida regalis Gray, and Lithospermum arvense L.), in terms of establishment success, seed production, and crop yield losses.A field experiment with partial additive design was performed in an organically managed winter rye stand with study species added in ten sowing rates of 5-10,000 seeds m(-2). They were sown as a single species or as a three-species mixture (pure vs. mixed sowing) and with vs. without removal of spontaneous weeds. Winter rye was sown at a fixed rate of 350 grains m(-2). Performance of the study species was assessed as plant establishment and seed production. Crop response was determined as grain yield.Plant numbers and seed production were significantly affected by the sowing rate, but not by sowing type (pure vs. mixed sowing of the three study species), and weed removal. All rare arable plant species established and reproduced at sowing rates >25 seeds m(-2), with best performance of L. speculum-veneris. Negative density effects occurred to some extent for plant establishment and more markedly for seed production.The impact of the three study species on crop yield followed sigmoidal functions. Depending on the species, a yield loss of 10% occurred at >100 seeds m(-2). Synthesis and applications: The study shows that reintroduction of rare arable plants by seed transfer is a suitable method to establish them on extensively managed fields, for example, in organic farms with low nutrient level and without mechanical weed control. Sowing rates of 100 seeds m(-2) for C. regalis and L. arvense, and 50 seeds m(-2) for L. speculum-veneris are recommended, to achieve successful establishment with negligible crop yield losses. PMID- 27551401 TI - Genetic diversity and structuring across the range of a widely distributed ladybird: focus on rear-edge populations phenotypically divergent. AB - Population genetics and phenotypic structures are often predicted to vary along the geographic range of a species. This phenomenon would be accentuated for species with large range areas, with discontinuities and marginal populations. We herein compare the genetic patterns of central populations of Coccinella septempunctata L. with those of two phenotypically differentiated populations considered as rear-edge populations and subspecies based on phenotype (Algeria and Japan). According to the central-marginal model and expected characteristics of rear-edge populations, we hypothesize that these rear-edge populations have (1) a reduced genetic diversity, resulting from their relative isolation over long periods of time, (2) a higher population genetic differentiation, explained by low contemporary gene flow levels, and (3) a relationship between genetic diversity characteristics and phenotypes, due to historical isolation and/or local adaptation. Based on genotyping of 28 populations for 18 microsatellite markers, several levels of regional genetic diversity and differentiation are observed between and within populations, according to their localization: low within-population genetic diversity and higher genetic differentiation of rear edge populations. The genetic structuring clearly dissociates the Algerian and Eastern Asia populations from the others. Geographical patterns of genetic diversity and differentiation support the hypothesis of the central-marginal model. The pattern observed is in agreement with the phenotypic structure across species range. A clear genetic break between populations of Algeria, the Eastern Asia, and the remaining populations is a dominant feature of the data. Differential local adaptations, absence of gene flow between marginal and central populations, and/or incapacity to mate after colonization, have contributed to their distinct genotypic and phenotypic characteristics. PMID- 27551402 TI - Modeling stream fish distributions using interval-censored detection times. AB - Controlling for imperfect detection is important for developing species distribution models (SDMs). Occupancy-detection models based on the time needed to detect a species can be used to address this problem, but this is hindered when times to detection are not known precisely. Here, we extend the time-to detection model to deal with detections recorded in time intervals and illustrate the method using a case study on stream fish distribution modeling. We collected electrofishing samples of six fish species across a Mediterranean watershed in Northeast Portugal. Based on a Bayesian hierarchical framework, we modeled the probability of water presence in stream channels, and the probability of species occupancy conditional on water presence, in relation to environmental and spatial variables. We also modeled time-to-first detection conditional on occupancy in relation to local factors, using modified interval-censored exponential survival models. Posterior distributions of occupancy probabilities derived from the models were used to produce species distribution maps. Simulations indicated that the modified time-to-detection model provided unbiased parameter estimates despite interval-censoring. There was a tendency for spatial variation in detection rates to be primarily influenced by depth and, to a lesser extent, stream width. Species occupancies were consistently affected by stream order, elevation, and annual precipitation. Bayesian P-values and AUCs indicated that all models had adequate fit and high discrimination ability, respectively. Mapping of predicted occupancy probabilities showed widespread distribution by most species, but uncertainty was generally higher in tributaries and upper reaches. The interval-censored time-to-detection model provides a practical solution to model occupancy-detection when detections are recorded in time intervals. This modeling framework is useful for developing SDMs while controlling for variation in detection rates, as it uses simple data that can be readily collected by field ecologists. PMID- 27551403 TI - Mixed pyolaryngocele: Uncommon presentation of deep spaces neck infection. AB - INTRODUCTION: Pyolaryngocele is a very rare and serious complication of laryngocoele. It can present as deep spaces neck infection and mislead the diagnosis. Our aim is to attract the intention of the surgeon to this unusual entity and describe its clinical features. CASE SUMMARY: We report a case of 45 years old male patient with five-week history of neck swelling, dysphonia, mild dyspnea and odynophagia. An urgent C.T scan showed a mixed pyolaryngocele. The management consisted high dose antibiotic and an excision of the residual laryngocoele via an external approach. DISCUSSION AND CONCLUSION: A pyolaryngocele is an unusual complication of laryngocoele that becomes secondarily infected causing serious symptoms. Excision of the laryngocoele, still the best treatment option to prevent this complication and recurrence. PMID- 27551404 TI - The change of neutrophils/lymphocytes ratio in migraine attacks: A case controlled study. AB - OBJECTIVE: As commonly seen symptoms, headaches are among the most frequently encountered health challenges in emergency rooms by healthcare professionals. Among one of the most commonly seen and primary headaches is migraine. Migraines are mostly accompanied by functional deficits. AIMS: To observe the changes of neutrophil/lymphocyte ratio occurring during migraine attacks. METHOD: This is a retrospective study where hospital records of patients previously diagnosed with migraine and admitted to the emergency with the complaints of attacks between May 2014 and January 2015 were investigated. All patients in the study were evaluated as to age, gender and complete blood count. Additionally, a healthy control group was formed with individuals with no disorders. By also evaluating the same features in the controls, the values found in the patients and controls alike were compared. RESULTS: The values of white blood cell, lymphocyte, neutrophil, hemoglobin, thrombocyte and neutrophil/lymphocyte ratio determined in the patient group (n = 92) were statistically compared with those of the controls (n = 67). Neutrophil/lymphocyte ratio during the attacks was found higher in the patients, compared to the controls. CONCLUSION: Neutrophil/lymphocyte ratio is a sign of inflammation, and we consider that this ratio will also increase during migraine attacks, as with other inflammatory and acute processes. PMID- 27551406 TI - Editorial. PMID- 27551405 TI - Accounting for multimorbidity can affect the estimation of the Burden of Disease: a comparison of approaches. AB - BACKGROUND: Various Burden of Disease (BoD) studies do not account for multimorbidity in their BoD estimates. Ignoring multimorbidity can lead to inaccuracies in BoD estimations, particularly in ageing populations that include large proportions of persons with two or more health conditions. The objective of this study is to improve BoD estimates for the Netherlands by accounting for multimorbidity. For this purpose, we analyzed different methods for 1) estimating the prevalence of multimorbidity and 2) deriving Disability Weights (DWs) for multimorbidity by using existing data on single health conditions. METHODS: We included 25 health conditions from the Dutch Burden of Disease study that have a high rate of prevalence and that make a large contribution to the total number of Years Lived with a Disability (YLD). First, we analyzed four methods for estimating the prevalence of multimorbid conditions (i.e. independent, independent age- and sex-specific, dependent, and dependent sex- and age specific). Secondly, we analyzed three methods for calculating the Combined Disability Weights (CDWs) associated with multimorbid conditions (i.e. additive, multiplicative and maximum limit). A combination of these two approaches was used to recalculate the number of YLDs, which is a component of the Disability Adjusted Life Years (DALY). RESULTS: This study shows that the YLD estimates for 25 health conditions calculated using the multiplicative method for Combined Disability Weights are 5 % lower, and 14 % lower when using the maximum limit method, than when calculated using the additive method. Adjusting for sex- and age-specific dependent co-occurrence of health conditions reduces the number of YLDs by 10 % for the multiplicative method and by 26 % for the maximum limit method. The adjustment is higher for health conditions with a higher prevalence in old age, like heart failure (up to 43 %) and coronary heart diseases (up to 33 %). Health conditions with a high prevalence in middle age, such as anxiety disorders, have a moderate adjustment (up to 13 %). CONCLUSIONS: We conclude that BoD calculations that do not account for multimorbidity can result in an overestimation of the actual BoD. This may affect public health policy strategies that focus on single health conditions if the underlying cost-effectiveness analysis overestimates the intended effects. The methodology used in this study could be further refined to provide greater insight into co-occurrence and the possible consequences of multimorbid conditions in terms of disability for particular combinations of health conditions. PMID- 27551407 TI - Assessing knowledge, perceptions and attitudes to pain management among medical and nursing students: a review of the literature. AB - INTRODUCTION: Chronic pain results in significant personal, societal and economic burden. Doctors and nurses have a pivotal role in patient pain management. In order to determine the effectiveness of current pain education on knowledge, attitudes and perceptions of medical and nursing students, there needs to be a valid measure to assess and quantify these domains. We reviewed the literature to identify approaches for assessing knowledge, perceptions and attitudes to pain management among nursing and medical students. METHODS: Databases of peer reviewed literature including CINAHL, EMBASE, ERIC, PsycInfo, Medline and PubMed were searched for articles published between 1993 and December 2014 using the following search terms: student, graduate, intern, junior, pain, pain management, analgesia, analgesic, pharmacology, pharmacological, knowledge, competence, attitude, preparedness, practice, nursing, medical, doctor, nurse. RESULTS: The search revealed over 3500 articles, and on application of the inclusion criteria, 26 articles were included in the review. A total of 14 instruments were used in these studies with the Knowledge and Attitudes Survey Regarding Pain (KASRP) as the main instrument in 9 out of the 26 articles. The various instruments used different question formats such as multiple-choice questions (MCQs), true/false statements and Likert scales that went from 3 points to 7 points. Clinical skills examinations were also used in four studies to assess pain management. CONCLUSION: There is no gold standard instrument currently used to assess knowledge, perceptions and attitudes to pain management. The results of this review showed, despite the diversity of standardised instruments that have been used to assess knowledge, perceptions and attitude to pain management, the literature has consistently reported that knowledge about pain management among nursing and medical students was generally poor among both groups. PMID- 27551408 TI - Introducing Acceptance and Commitment Therapy to a physiotherapy-led pain rehabilitation programme: an Action Research study. AB - BACKGROUND: Recent developments in pain rehabilitation emphasise the importance of promoting psychological flexibility. Acceptance and Commitment Therapy (ACT) is one approach that has been shown to be effective for the treatment of chronic musculoskeletal pain. However, studies have shown that introducing innovative approaches such as ACT into established health care can cause some anxiety for professional groups. We used Action Research to evaluate the implementation of ACT to a physiotherapy-led pain rehabilitation programme. METHODS: All staff in the pain service were invited to participate. Participants took part in focus groups, engaged in reflective sessions/meetings and completed reflective diaries. The analysis was undertaken by an experienced qualitative researcher using constant comparison. Participants reviewed emerging themes and validated the findings. RESULTS: Four key themes emerged from the study: (a) the need to see pain as an embodied, rather than dualistic, experience; (b) the need for a more therapeutic construction of 'acceptance'; (c) value-based goals as profound motivation for positive change; and (d) it's quite a long way from physiotherapy. Integral to a therapeutic definition of acceptance was the challenge of moving away from 'fixing' towards 'sitting with'. Participants described this as uncomfortable because it did not fit their biomedical training. CONCLUSION: This article describes how Action Research methodology was used in the introduction of ACT to a physiotherapy-led pain rehabilitation programme. The innovation of this study is that it helps us to understand the potential barriers and facilitators to embedding an ACT philosophy within a physiotherapy setting. PMID- 27551409 TI - Towards a pain free hospital: an in-depth qualitative analysis of the pain experiences of head and neck cancer patients undergoing radiotherapy. AB - BACKGROUND: Treatment for head and neck cancer can frequently be a painful experience with implications for patients in terms of quality of life, nutrition and ultimately treatment outcomes. Pain may arise for a number of reasons in this patient group including the influence of localised tissue damage from radiotherapy, the effects of chemotherapeutic agents as well as the disease process itself. Early identification of cancer pain, through screening and early analgesic and pain management are thought to be the most appropriate approaches to the problem. AIM: To explore in-depth, patients' views of the experience of pain related to radiotherapy for head and neck cancer, within the context of a randomised controlled trial (RCT) of pain screening and intervention. SAMPLE: A purposive sample of head and neck cancer patients undergoing radiotherapy who were participating in a separate RCT of a proactive pain screening intervention. METHODS: A qualitative design using one-off, face-to-face, in-depth interviews. Data were inductively analysed for themes using thematic analysis. Data were collected from September 2012 to January 2013. FINDINGS: Eight participants were interviewed. Several issues around pain management arose and the influence of various factors became apparent. Four dominant themes emerged: facets of radiotherapy pain in head and neck cancer, facilitators and barriers to pain management, pain services and finally interdisciplinary working. CONCLUSION: The specific issues faced by head and neck cancer patients undergoing radiotherapy highlight the need for pain relieving interventions delivered by pain specialists, in tandem with the development of robust self-management strategies. An integrated approach to care is optimal, comprising pain screening at each outpatient encounter, and review by specialists as necessary. PMID- 27551410 TI - Brief psychologically informed physiotherapy training is associated with changes in physiotherapists' attitudes and beliefs towards working with people with chronic pain. AB - This study aimed to investigate the impact of a brief psychologically informed physiotherapy training (PIPT) course on physiotherapists' attitudes and beliefs towards working with people with chronic pain. Specifically, the training aimed to help the participants better recognise the role of psychosocial factors in chronic pain and to better target the key processes of the psychological flexibility (PF) model in their treatment interactions. A total of 26 physiotherapists working in an outpatient musculoskeletal (MSK) department participated in the 7-hour training session. A total of 25 participants completed self-report questionnaires on attitudes and beliefs, burnout and PF-relevant processes pre- and post-training. The pre- and post-measures were completed on the day of training. PIPT was associated with significant changes in the expected direction in physiotherapists' attitudes towards treatment of people with chronic pain, including a moderate effect size on the Health Care Provider-Pain and Impairment Relationship Scale (HC-PAIRS) (decreased biomedical scores) and a large effect size on the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) (increased biopsychosocial scores and decreased biomedical scores). In conclusion, brief PIPT could help physiotherapists working in non-specialist centres with complex patients, many of whom present with significant emotional distress and pain-related disability. Further research is required to determine whether the changes in attitudes detected in this study translate into clinical practice and whether changes are maintained over a follow-up period. PMID- 27551413 TI - Editorial. PMID- 27551411 TI - Clinical effectiveness of a residential pain management programme - comparing a large recent sample with previously published outcome data. AB - OBJECTIVE: Observational studies using routinely collected data indicate that pain management programmes (PMPs) based on cognitive-behavioural principles are associated with clinically meaningful improvements for individuals with chronic pain. This study evaluated change across functional measures in a sample of chronic pain patients attending a 4-week residential PMP between 2006 and 2010. The findings were directly compared with published outcomes from an earlier period (1989-1998) at the same service. METHODS: Participants included 760 consecutive completers of a multidisciplinary PMP. Data were collected at pre PMP, post-PMP (1-month post-discharge) and at a 9-month follow-up session. Group based treatment effects and the reliability and clinical significance of change across functional measures were calculated and compared across cohorts. RESULTS: Effect sizes for the recent cohort ranged from small to medium (.43-.67) for pain and physical functioning outcomes to large (.90-1.12) for psychological outcomes at post-treatment (n = 654), and from small (.30-.51) to medium (.58-.71) at 9 month follow-up (n = 493). Clinically significant gains on pain and psychological measures were achieved by 19-55% of patients at post-treatment and 17-44% at follow-up. Comparisons with the earlier cohort showed significantly stronger post treatment outcomes but differences at follow-up were less marked. DISCUSSION: These results add to the evidence base supporting the effectiveness of cognitive behavioural therapy (CBT)-based pain management interventions. There were significantly larger gains in patient functioning in the recent dataset, suggesting improved programme delivery. But effects were less marked in the longer term, indicating a need for improvements in therapeutic models and related methods to promote meaningful and lasting changes. PMID- 27551414 TI - The French Syrette of morphine for administration to combat casualties. PMID- 27551415 TI - Intrathecal drug delivery for the management of pain and spasticity in adults: an executive summary of the British Pain Society's recommendations for best clinical practice. AB - This article provides a summary of the updated British Pain Society Guidance on Intrathecal Drug Delivery for the management of pain and spasticity in adults. We aim to highlight the areas of the guidance that have been updated and to provide a concise summary. PMID- 27551416 TI - Perceptions of phantom limb pain in lower limb amputees and its effect on quality of life: a qualitative study. AB - BACKGROUND: Phantom limb pain (PLP) is a prevalent complication post-amputation. Currently, qualitative literature exploring the experience of PLP in amputees is sparse, and little is known about whether the educational needs of amputees are being met. OBJECTIVES: To explore lower limb amputees' descriptive lived experiences of PLP, to understand how PLP affects quality of life and to determine whether amputees feel they are provided with adequate information about PLP. METHODS: A qualitative descriptive approach, situated under the constructivist paradigm was taken, consisting of cross-sectional semi-structured interviews. A purposive sample of 15 lower limb amputees, 1-3 months post-surgery with past or current experience of PLP were interviewed once about their experience of PLP. Interviews were audio-recorded, transcribed verbatim and analysed using Framework Analysis. Interviews were conducted while participants were inpatients at an amputee rehabilitation unit in London. RESULTS: Six key themes were identified during analysis, of which three were related to PLP and are reported on in this article (real and physical phantoms, living with a phantom and being informed). PLP had numerous painful qualities. The phantom felt real, with kinetic and kinaesthetic properties. PLP had multiple meanings to amputees, was considered a reminder of circumstances and could affect quality of life. Information provided about PLP was inadequate. CONCLUSION: PLP can be a severe and annoying experience acting as a reminder of amputees' circumstances. Information provided about PLP is inadequate, with some amputees still perceiving PLP as mental and imaginary. Education about PLP and awareness and accessibility to non-pharmacological interventions needs to be improved. PMID- 27551417 TI - 'Pseudofailure' of spinal cord stimulation for neuropathic pain following a new severe noxious stimulus: learning points from a case series of failed spinal cord stimulation for complex regional pain syndrome and failed back surgery syndrome. AB - Failure of spinal cord stimulation (SCS) may be due to hardware problems, migration of electrodes and, in the long-term, plasticity in the spinal cord with habituation to the stimulation current. We describe a series of seven patients who experienced acute therapeutic loss of SCS effects following an acute nociceptive event unrelated to primary pathology. There were no hardware problems. We called this 'Pseudofailure', as the effective stimulation returned in all patients following a period off stimulation or reprogramming. This phenomenon has not been reported previously in the literature. Over a 4-year period, we managed seven patients with this feature: four had received SCS for complex regional pain syndrome and three for failed back surgery syndrome. In all seven cases, there was cessation of the pain relief afforded by SCS following an acute painful event: four patients had trauma, two patients had domestic electric shock and one patient suffered shingles (varicella zoster infection). We excluded hardware-related problems in all cases. In two patients, SCS effects could be regained by an initial attempt at reprogramming. In the remaining five cases reprogramming was unsuccessful, and stimulation was switched off for several months before recommencing, when we discovered a return of good therapeutic effect. We conclude that SCS may seem to fail following a separate strong nociceptive stimulus. Stimulation may be regained with reprogramming or following a period with stimulation switched off. We would, therefore, advise against removal of SCS hardware in the first instance. PMID- 27551418 TI - Patient compliance with postoperative analgesia after day case surgery: a multisite observational study of patients in North East London. AB - BACKGROUND: Pain is the commonest reason for delayed discharge and readmission post day surgery with up to 45% of patients reported to suffer moderate-to-severe post-surgical pain 24 hours after discharge. The importance of post-surgical pain management extends beyond the acute phase when one considers that all chronic post-surgical pain was once acute. Although much focus is given to perioperative analgesia, a patient's pain management once discharged can be overlooked, whilst at this time the patient's pain management is within their own hands. METHODS: We conducted this multisite observational study of adult patients undergoing day case surgery. After obtaining patient consent data was collected on the operation, intra- and postoperative analgesia administered and discharge analgesia prescribed. Patients were then contacted at home by telephone 48 hours after discharge and asked about their postoperative pain and analgesia requirements. RESULTS: Of 150 patients consented for the enrolment, we were able to obtain postoperative analgesia data on 100. A total of 68% of patients reported pain following discharge with 26% reporting severe pain, defined as a pain score of ?7. A total 68% of patients were prescribed and dispensed analgesia, and of those, 83% were compliant with their analgesia. Thus, we conclude that in this patient group, the incidence of postoperative pain was not due to lack of patient compliance, but inadequate analgesia prescription. DISCUSSION: We recognise that our data reflect a patient population in North East London but suggest that the results may still be relevant to a wider patient group across the United Kingdom as the incidence of postoperative pain in our study was similar to published figures. Better patient satisfaction with postoperative analgesia may be obtained with more patient- and surgery-specific analgesic prescription. PMID- 27551419 TI - 'Simplicity' radiofrequency neurotomy of sacroiliac joint: a real life 1-year follow-up UK data. AB - BACKGROUND: Sacroiliac joint (SIJ) pain is considered to be the third most common cause of low back pain with the prevalence of 13-25% in all low back pain patients. Its diagnosis and treatment remain a challenge with the poor evidence base for interventional procedures. Patients with SIJ pain experience a low quality of life, worse than some of the chronic health conditions. Simplicity radiofrequency (RF) neurotomy is a novel technique which tackles some of the problems faced by conventional RF neurotomy and may offer better results in managing pain arising from SIJ. AIM: The purpose of this retrospective review of practice was to look into the effectiveness of Simplicity RF neurotomy in terms of pain relief, quality of health improvement in patients suffering from SIJ pain and complications associated with the procedure. METHODOLOGY: Retrospective review of the patients undergoing Simplicity RF neurotomy at a tertiary hospital (April 2012 to June 2013). Pain scores and responses to SF (Short Form) 12 questionnaire before and at 12 months after treatment were compared using the Wilcoxon signed-rank test. RESULTS: Out of 26 patients, 16 were considered for analysis. There was statistically significant reduction in both mean pain score (Numerical Rating Scale, NRS from 8.8 pre-intervention to 4.3 post-intervention) and median pain score (NRS from 9 pre-intervention to 5 post-intervention) with a p-value of <0.001 at 12 months. Reduction in the inter-quartile range of pain score was observed from 8-10 to 2.25-6 (p-value of <0.001). Global health as per SF12 scores showed statistically significant improvement, except in some of the psychological subcategories. The procedure-related pain was the only complication noted. CONCLUSION: From our data, we can conclude that Simplicity RF neurotomy of lateral branches of S1-S3 along with conventional RF denervation of L5 dorsal ramus may improve pain scores and many components of global health in carefully selected patients. PMID- 27551420 TI - Understanding factors that facilitate the inclusion of pain education in undergraduate curricula: Perspectives from a UK survey. AB - BACKGROUND: Studies in Europe, North America and Australasia suggest that one in five adults suffer from pain. There is increasing recognition that pain, particularly chronic pain, represents a global health burden. Many studies, including two national surveys exploring the content of undergraduate curricula for pain education, identify that documented pain education in curricula was limited and fragmentary. METHODS: The study design used a questionnaire which included an open text comment box for respondents to add 'further comments' as part of larger study previously published. The sample consisted of 19 UK universities that offered 108 undergraduate programmes in the following: dentistry, medicine, midwifery, nursing (adult, child, learning disabilities and mental health branches), occupational therapy (OT), pharmacy, physiotherapy and veterinary science. An inductive content analysis was performed, and the data were managed using NVivo 10 software for data management. RESULTS: A total of 57 participants across seven disciplines (dentistry, medicine, midwifery, nursing, pharmacy, physiotherapy and OT) completed the open text comment box (none were received from veterinary science). Analysis revealed two major themes of successes and challenges. Successes included expansion (extending coverage and/or increased student access), multidimensional curriculum content and diversity of teaching methods. Challenges included difficulties in identifying where pain is taught in the curriculum, biomedical versus biopsychosocial definitions of pain, perceived importance, time, resources and staff knowledge, and finally a diffusion of responsibility for pain education. CONCLUSION: This study identifies new insights of the factors attributed to successful implementation of pain education in undergraduate education. Many of the challenges previously reported were also identified. This is one of the first studies to identify a broad range of approaches, for pain education, that could be deemed as 'successful' across a range of health disciplines. PMID- 27551421 TI - Does preoperative psychological status of patients affect postoperative pain? A prospective study from the Caribbean. AB - OBJECTIVES: Patients with high anxiety states in the preoperative period often have more intense postoperative pain, despite adequate pain control during the intraoperative period. This study aimed to determine the relationship between the preoperative psychological status and the pain experienced postoperatively in a sample of Caribbean patients. DESIGN AND METHODS: A prospective study was conducted in elective surgical adult patients at a teaching hospital in the Caribbean. Patients' preoperative psychological status was assessed using Hospital Anxiety and Depression Scale (HADS), and a preoperative 'expected' pain score was recorded. Postoperatively, 'observed' pain scores at 4 and 24 hours and the maximum pain score during 24 hours were recorded. Demographic data and clinical details including data regarding postoperative analgesia were collected. Expected and observed pain scores were compared between patients with and without anxiety and depression. RESULTS: A total of 304 patients were enrolled. The overall prevalence of anxiety and depression was 43% and 27%, respectively, based on the HADS scores. There were significant associations between the postoperative pain scores and factors such as preoperative anxiety and depression (HADS) scores, preoperative expected pain scores, patient educational level, presence of preoperative pain and surgical duration. Age, gender, ethnicity and type of anaesthesia did not impact postoperative pain scores. CONCLUSION: The presence of preoperative anxiety and depression as indicated by HADS score may significantly influence postoperative pain. Other factors such as educational level, presence of preoperative pain and surgical duration may also impact postoperative pain. Some of these factors may be modifiable and must be addressed in the preoperative period. PMID- 27551422 TI - Burden of upper gastrointestinal symptoms in patients prescribed dabigatran for stroke prevention. AB - BACKGROUND: Dabigatran, a non-vitamin K antagonist oral anticoagulant, has been shown to prevent stroke in patients with non-valvular atrial fibrillation. Nonetheless, studies show that 10%-30% of those prescribed dabigatran experience dyspepsia that may eventually lead to discontinuation of therapy and loss of clinical benefit. AIM: To evaluate the gastrointestinal tolerability of dabigatran utilizing a validated questionnaire, as well as determining subsequent non-compliance and drug discontinuation. METHOD: This is an observational study. All patients were assessed by a validated questionnaire, Hong Kong dyspepsia index, prior to drug prescription and again 4 weeks later. RESULTS: In this study, 115 patients with non-valvular atrial fibrillation (mean age: 74.6 +/- 11.4 years; mean CHA2DS2-VASc score was 3.39 +/- 1.59) were prescribed dabigatran. At baseline, the mean Hong Kong dyspepsia index was 12.9 +/- 1.6 and nine patients had significant dyspepsia (Hong Kong dyspepsia index ? 16). After 4 weeks, the mean Hong Kong dyspepsia index was similar at 12.6 +/- 1.9 (p = 0.23). There was no change in Hong Kong dyspepsia index after initiation of dabigatran in 59 (51.3%) patients, and improvement in 37 (32.2%). Only 19 (16.5%) patients had worsening of Hong Kong dyspepsia index, and among these 19 patients, only 1 patient (0.9%) discontinued dabigatran due to significant dyspepsia. CONCLUSION: Worsening of dyspepsia with dabigatran 110 mg twice daily was uncommon with correct drug administration and clear instructions provided. Systematic assessment of dyspeptic symptoms using a validated questionnaire (i.e. Hong Kong dyspepsia index) before and after treatment initiation allows a more objective comparison of dyspeptic symptoms. PMID- 27551423 TI - A survey exploring the knowledge and perceptions of senior medical students in Nepal toward generic medicines. AB - BACKGROUND: The accurate knowledge of generic medicine issues among future prescribers will enhance the prescribing of cost-effective medicines. This study aimed to explore the knowledge and perception of senior medical students about the generic medicines. METHODOLOGY: A cross-sectional study was conducted among 237 senior medical students (final year students and interns) using a validated self-administered questionnaire. The collected data were analyzed using Statistical Package for the Social Sciences version 20 for windows and comparison of difference was done using linear by linear association. A p value of less than 0.05 was taken as statistically significant. RESULTS: The average age (standard deviation) of the respondents was 23.54 (1.39) years. Almost 5% of respondents correctly answered the question regarding the regulatory limits for bioequivalence. Almost two-thirds of respondents correctly agreed that generic medicine is bioequivalent to a brand-name medicine, and 79.3% and 72.5% of respondents correctly agreed that the medicine should be present in the same dosage form and same dose, respectively, as the brand-name medicines. However, almost half of the respondents had impression that brand-name medicines are required to meet higher safety standard than generic medicines. Almost 90% of respondents felt that advertisement by the drug companies would influence the use of brand-name medicine and they need more information about generic medicine. CONCLUSION: This study highlights the negative perception and knowledge deficit among the respondents. The students' responses to almost all the statements were almost similar to the respondents' academic year (final year students and interns), gender and nationality. PMID- 27551424 TI - Recruitment of general practices: Is a standardised approach helpful in the involvement of healthcare professionals in research? AB - INTRODUCTION: Health service research often involves the active participation of healthcare professionals. However, their ability and commitment to research varies. This can cause recruitment difficulties and thereby prolong the study period and inflate budgets. Solberg has identified seven R-factors as determinants for successfully recruiting healthcare professionals: relationships, reputation, requirements, rewards, reciprocity, resolution, and respect. METHOD: This is a process evaluation of the seven R-factors. We applied these factors to guide the design of our recruitment strategy as well as to make adjustments when recruiting general practices in a guideline implementation study. In the guideline implementation study, we studied the effect of outreach visits, quality reports, and new patient stratification tools for low back pain patients. RESULTS: During a period of 15 months, we recruited 60 practices, which was fewer than planned (100 practices). In this evaluation, five of Solberg's seven R factors were successfully addressed and two factors were not. The need to involve (reciprocity) end users in the development of new software and the amount of time needed to conduct recruitment (resolution) were underestimated. CONCLUSION: The framework of the seven R-factors was a feasible tool in our recruitment process. However, we suggest further investigation in developing systematic approaches to support the recruitment of healthcare professionals to research. PMID- 27551425 TI - Transarterial embolization for management of severe postcoital bleeding. AB - OBJECTIVES: Postcoital bleeding is an uncommon cause of gynecologic hemorrhage; however, it can be severe in a majority of cases necessitating surgical management. METHODS: We report a case of severe postcoital bleeding in a young woman requiring blood transfusion. RESULTS: Hemostasis was achieved using subselective embolization of cervical artery by metallic coils. CONCLUSION: Our case demonstrates a minimally invasive treatment for control of non-obstetric hemorrhage. PMID- 27551426 TI - Substrate Modulus Regulates Osteogenic Differentiation of Rat Mesenchymal Stem Cells through Integrin beta1 and BMP Receptor Type IA. AB - Osteoblast differentiation of mesenchymal stem cells is regulated by both soluble factor (e.g., bone morphogenetic proteins (BMP)) and mechanically transduced signaling, but the mechanisms have only been partially elucidated. In this study, physical association of BMP Receptor I (BMPRI) with integrin beta1 sub-unit (Ibeta1) was hypothesized to mediate osteoblast differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) on bone-like substrates. The effects of substrate modulus on osteoblast differentiation of MSCs were investigated for 2D poly(ester urethane) films with moduli varying from 5 - 266 MPa, which spans the range from collagen fibrils to trabecular bone. SMAD1/5 and p44/42 MAPK signaling, expression of markers of osteoblast differentiation, and matrix mineralization increased with increasing substrate modulus. The effects of substrate modulus on osteoblast differentiation were mediated by Ibeta1, which was also expressed at higher levels on increasingly rigid substrates. Forster resonance energy transfer (FRET) and immunoprecipitation (IP) experiments showed that physical association of Ibeta1 and BMP Receptor I (BMRPRI) increased with substrate modulus, resulting in activation of the BMP signaling pathway. Thus, these studies showed that integrin and BMP signaling converge to regulate osteoblast differentiation of MSCs, which may potentially guide the design of scaffolds and rhBMP-2 delivery systems for bone regeneration. PMID- 27551427 TI - Intentions to receive a potentially available Lyme disease vaccine in an urban sample. AB - OBJECTIVES: The only human Lyme disease vaccine of LYMErix was voluntarily removed from the market in the United States in 2002 for a number of reasons. A new human Lyme disease vaccine is currently being developed. We would like any future approved human Lyme disease vaccine to be of interest and marketable to consumers. METHODS: We surveyed 714 participants to determine variables associated with intentions to receive a Lyme disease vaccine. Predictor variables included demographics, protection motivational theory, Lyme disease knowledge, Lyme disease preventive behaviors, beliefs and perceived health. RESULTS: We found in multivariate linear regression analyses that Asian/Asian American race/ethnicity (p < 0.001), South Asian race/ethnicity (p = 0.01) and coping appraisal variables of response efficacy (p < 0.001) and self-efficacy (p < 0.001) were each significantly associated with increased intentions. The belief that vaccines are typically not safe was significantly associated with decreased intentions (p = 0.03). CONCLUSIONS: Asian/Asian American and South Asian race/ethnicities have a strong interest in receiving a Lyme disease vaccine. Although pharmaceutical companies may benefit by advertising a Lyme disease vaccine to Asian/Asian Americans and South Asians, marketers need to address and use approaches to interest those from other race/ethnicities. Also, marketers need to address the erroneous belief that vaccines are typically not safe in order to interest those with such beliefs to use a Lyme disease vaccine. PMID- 27551428 TI - Neisseria meningitidis and Streptococcus pneumoniae as leading causes of pediatric bacterial meningitis in nine Mexican hospitals following 3 years of active surveillance. AB - OBJECTIVES: Meningococcal meningitis is reported as a rare condition in Mexico. There are no internationally published studies on bacterial causes of meningitis in the country based on active surveillance. This study focuses on finding the etiology of bacterial meningitis in children from nine Mexican Hospitals. METHODS: From January 2010 to February 2013, we conducted a three years of active surveillance for meningitis in nine hospitals throughout Mexico. Active surveillance started at the emergency department for every suspected case, and microbiological studies confirmed/ruled out all potentially bacterial pathogens. We diagnosed based on routine cultures from blood and cerebrospinal fluid (not polymerase chain reaction or other molecular diagnostic tests), and both pneumococcal serotyping and meningococcal serogrouping by using standard methods. RESULTS: Neisseria meningitidis was the leading cause, although 75% of cases occurred in the northwest of the country in Tijuana on the US border. Serogroup C was predominant. Streptococcus pneumoniae followed Neisseria meningitides, but was uniformly distributed throughout the country. Serotype 19A was the most incident but before universal implementation of the 13-valent pneumococcal conjugate vaccine. Other bacteria were much less common, including Enterobacteriaceae and Streptococcus agalactiae (these two affecting mostly young infants). CONCLUSIONS: Meningococcal meningitis is endemic in Tijuana, Mexico, and vaccination should be seriously considered in that region. Continuous universal vaccination with the 13-valent pneumococcal conjugate vaccine should be nationally performed, and polymerase chain reaction should be included for bacterial detection in all cultures - negative but presumably bacterial meningitis cases. PMID- 27551430 TI - Erratum. AB - [This corrects the article DOI: 10.1177/2051013615599151.]. PMID- 27551429 TI - Efficacy of varicella (VZV) vaccination: an update for the clinician. AB - Varicella-zoster virus (VZV) infection causes two distinct clinical conditions. Primary varicella infection results in chickenpox, a contagious rash illness typically seen among children. VZV can reactivate years after the initial infection to cause herpes zoster (HZ) and lead to post-herpetic neuralgia, a common complication resulting in persistent pain that may last for years after the zoster rash resolves. A person's risk of having longer lasting and more severe pain associated with HZ increases with age. Since the introduction of VZV vaccines, the rates of infection, hospitalizations, and mortality have declined. In this review, we discuss in detail current VZV vaccines available for the prevention of VZV and HZ infections. Varilrix (GSK Biologicals, UK), Varivax (Merck, USA) and the combined measles, mumps, rubella, and varicella (MMRV) vaccine contain the live attenuated Oka strain of VZV for routine varicella vaccination. While Zostavax is the only HZ vaccine currently approved for use in the United States and the European Union [EMEA, 2011], a subunit vaccine candidate called HZ/su has recently shown improved efficacy for zoster prevention in two clinical trial phase III studies. VariZIG, a post-exposure prophylactic, uses zoster immune globulin to prevent VZV infection in those who have recently been in contact with VZV but lack evidence of varicella immunity and are contraindicated to receive the varicella vaccine. Further, we discuss the skin tropic and neurotropic factor VZV ORF7 gene and its involvement in varicella infection, reactivation and latency in ganglia. Ultimately, these studies can contribute to the development of a neuroattenuated vaccine candidate against varicella or a vector for delivery of other virus antigens. PMID- 27551431 TI - Rickettsiologist Pavel F. Zdrodovskii: larger than life, and not just for his famous book. AB - This article highlights the biography and scientific accomplishments of Pavel F. Zdrodovskii and his contributions to understanding the biology, pathogenesis, treatment, prevention and epidemiology of brucellosis, rickettsioses and many other infectious diseases. PMID- 27551432 TI - Temozolomide treatment of pituitary carcinomas and atypical adenomas: systematic review of case reports. AB - BACKGROUND: Pituitary carcinomas (PC) and atypical pituitary adenomas (APA) are rare variants of pituitary tumors for which no evidence-based treatment currently exists. We sought to determine whether temozolomide represents an effective chemotherapeutic option for patients with PC and APA. METHODS: A systematic review was performed using all published cases of PC and APA treated with temozolomide, and for which information on treatment regimen, clinical response, and survival could be identified. The primary goal of this analysis was to describe overall survival and progression-free survival among PC and APA patients after temozolomide treatment. Secondary goals included assessment of response rate and biomarkers of response. RESULTS: We identified 57 cases and obtained follow-up data on 54 patients (31 APA and 23 PC) for analysis. Estimates of 5 year progression-free survival and overall survival were 21.9% and 57.4% for patients with APA and 36.1% and 56.2% for patients with PC. Among those who responded to temozolomide, overall survival was marginally statistically significantly greater for patients on long-term temozolomide therapy compared with those who were not (5-year overall survival 91.7% vs 54.1%, P = .08); Progression-free survival results were similar but not statistically significant. The objective response rate was 48.4% for patients with APA and 65.2% for patients with PC. Stable disease occurred in 29% of APA and 17.4% of PC patients. Neither histology nor expression of Ki-67 correlated with response; however, negative O6-methylguanine-DNA methyltransferase staining was strongly related to response to temozolomide in patients with APA (P < .001). CONCLUSIONS: Temozolomide is an effective treatment of both PC and APA, and long-term treatment can be considered for particularly aggressive cases. PMID- 27551433 TI - Effects of persimmon peel supplementation on pork quality, palatability, fatty acid composition, and cholesterol level. AB - BACKGROUND: The objectives of this study were to investigate the effects of persimmon peel (PPM) supplementation on carcass performance, pork quality, eating quality, fatty acid composition, and cholesterol concentration of the porcine longissimus dorsi muscle. RESULTS: No adverse effects of PPM supplementation were observed on carcass and meat quality characteristics among the treatment groups (P > 0.05), whereas pork loins from pigs fed a diet supplemented with 0.9 % persimmon peel (T3) showed more tender meat than did pork loins from pigs fed a control diet (P < 0.01), even though no significant difference was observed between the control and T1 group. The T3 group had higher ratio of polyunsaturated fatty acids relative to saturated fatty acids (0.33 vs. 0.28, P < 0.05) and lower total cholesterol concentration (94.4 vs. 99.1 mg/g, P < 0.05) compared to the control group. Persimmon peel appeared to have beneficial effects on fatty acid composition and cholesterol concentration, probably leading to a hypocholesterolemic effect. CONCLUSIONS: Animal diets fortified with persimmon peel represents an efficient and useful method for improving the nutritional quality of pork without impairing growth performance and eating quality properties. PMID- 27551434 TI - MAVS maintains mitochondrial homeostasis via autophagy. AB - Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS mediated antiviral signalling contributes to mitochondrial homeostasis. Here we show that the activation of MAVS is sufficient to induce autophagic signalling, which may mediate the turnover of the damaged mitochondria. Importantly, we find MAVS directly interacts with LC3 through its LC3-binding motif 'YxxI', suggesting that MAVS might act as an autophagy receptor to mediate mitochondrial turnover upon excessive activation of RLR signalling. Furthermore, we provide evidence that both MAVS self-aggregation and its interaction with TRAF2/6 proteins are important for MAVS-mediated mitochondrial turnover. Collectively, our findings suggest that MAVS acts as a potential receptor for mitochondria-associated autophagic signalling to maintain mitochondrial homeostasis. PMID- 27551435 TI - The chromatin remodeler DDM1 promotes hybrid vigor by regulating salicylic acid metabolism. AB - In plants, hybrid vigor is influenced by genetic and epigenetic mechanisms; however, the molecular pathways are poorly understood. We investigated the potential contributions of epigenetic regulators to heterosis in Arabidposis and found that the chromatin remodeler DECREASED DNA METHYLATION 1 (DDM1) affects early seedling growth heterosis in Col/C24 hybrids. ddm1 mutants showed impaired heterosis and increased expression of non-additively expressed genes related to salicylic acid metabolism. Interestingly, our data suggest that salicylic acid is a hormetic regulator of seedling growth heterosis, and that hybrid vigor arises from crosses that produce optimal salicylic acid levels. Although DNA methylation failed to correlate with differential non-additively expressed gene expression, we uncovered DDM1 as an epigenetic link between salicylic acid metabolism and heterosis, and propose that the endogenous salicylic acid levels of parental plants can be used to predict the heterotic outcome. Salicylic acid protects plants from pathogens and abiotic stress. Thus, our findings suggest that stress induced hormesis, which has been associated with increased longevity in other organisms, may underlie specific hybrid vigor traits. PMID- 27551436 TI - Forkhead containing transcription factor Albino controls tetrapyrrole-based body pigmentation in planarian. AB - Pigmentation processes occur from invertebrates to mammals. Owing to the complexity of the pigmentary system, in vivo animal models for pigmentation study are limited. Planarians are capable of regenerating any missing part including the dark-brown pigments, providing a promising model for pigmentation study. However, the molecular mechanism of planarian body pigmentation is poorly understood. We found in an RNA interference screen that a forkhead containing transcription factor, Albino, was required for pigmentation without affecting survival or other regeneration processes. In addition, the body color recovered after termination of Albino double stranded RNA feeding owing to the robust stem cell system. Further expression analysis revealed a spatial and temporal correlation between Albino and pigmentation process. Gene expression arrays revealed that the expression of three tetrapyrrole biosynthesis enzymes, ALAD, ALAS and PBGD, was impaired upon Albino RNA interference. RNA interference of PBGD led to a similar albinism phenotype caused by Albino RNA interference. Moreover, PBGD was specifically expressed in pigment cells and can serve as a pigment cell molecular marker. Our results revealed that Albino controls planarian body color pigmentation dominantly via regulating tetrapyrrole biogenesis. These results identified Albino as the key regulator of the tetrapyrrole-based planarian body pigmentation, suggesting a role of Albino during stem cell-pigment cell fate decision and provided new insights into porphyria pathogenesis. PMID- 27551437 TI - Sphingolipids modulate the epithelial-mesenchymal transition in cancer. PMID- 27551438 TI - CDDiscovery. PMID- 27551439 TI - WWOX dysfunction induces sequential aggregation of TRAPPC6ADelta, TIAF1, tau and amyloid beta, and causes apoptosis. AB - Aggregated vesicle-trafficking protein isoform TRAPPC6ADelta (TPC6ADelta) has a critical role in causing caspase activation, tau aggregation and Abeta generation in the brains of nondemented middle-aged humans, patients with Alzheimer's disease (AD) and 3-week-old Wwox gene knockout mice. WWOX blocks neurodegeneration via interactions with tau and tau-phosphorylating enzymes. WWOX deficiency leads to epilepsy, mental retardation and early death. Here, we demonstrated that TGF-beta1 induces shuttling of endogenous wild-type TPC6A and TPC6ADelta in between nucleoli and mitochondria (~40-60 min per round trip), and WWOX reduces the shuttling time by 50%. TGF-beta1 initially maximizes the binding of TPC6ADelta to the C-terminal tail of WWOX, followed by dissociation. TPC6ADelta then undergoes aggregation, together with TIAF1 (TGF-beta1-induced antiapoptotic factor), in the mitochondria to induce apoptosis. An additional rescue scenario is that TGF-beta1 induces Tyr33 phosphorylation and unfolding of WWOX and its the N-terminal WW domain slowly binds TPC6ADelta to block aggregation and apoptosis. Similarly, loss of WWOX induces TPC6ADelta polymerization first, then aggregation of TIAF1, amyloid beta and tau, and subsequent cell death, suggesting that a cascade of protein aggregation leads to neurodegeneration. PMID- 27551440 TI - miRNAs in mtDNA-less cell mitochondria. AB - The novel regulation mechanism in mtDNA-less cells was investigated. Very low mtDNA copy in mtDNA-less 206 rho degrees cells was identified. But no 13 mitochondria-specific proteins were translated in 206 rho degrees cells. Their mitochondrial respiration complexes V, III and II were 86.5, 29.4 and 49.6% of 143B cells, respectively. Complexes I and IV completely lack in 206 rho degrees cells. Non-mitochondrial respiration to generate ATP in 206 rho degrees cells was discovered. The expression levels of some mitochondrial RNAs including 12S rRNA, COX1, COX2, COX3, ND4 and ND5 were low. However, ND1, ND3 and Cyto b were not expressed in 206 rho degrees cells. Unequal transcription of mitochondrial RNAs indicated the post-transcriptional cleavage and processing mechanisms in the regulation of mitochondrial gene expression in 206 rho degrees cells. MicroRNAs (miRNAs) may modulate these mitochondrial RNA expression in these cells. RNA induced silencing complex indeed within 206 rho degrees cell mitochondria indicated miRNAs in 206 rho degrees cell mitochondria. miRNA profile in mtDNA less 206 rho degrees cells was studied by next-generation sequencing of small RNAs. Several mitochondria-enriched miRNAs such as miR-181c-5p and miR-146a-5p were identified in 206 rho degrees cell mitochondria. miR-181c-5p and miR-146a 5p had 23 and 19 potential targets on mitochondrial RNAs respectively, and these two miRNAs had multiple targets on mitochondria-associated messenger RNAs encoded by nuclear genes. These data provided the first direct evidence that miRNAs were imported into mitochondria and regulated mitochondrial RNA expressions. PMID- 27551441 TI - Post-translational allosteric activation of the P2X7 receptor through glycosaminoglycan chains of CD44 proteoglycans. AB - Here, we present evidence for the positive allosteric modulation of the P2X7 receptor through glycosaminoglycans (GAGs) in CHO (cell line derived from the ovary of the Chinese hamster) cells. The marked potentiation of P2X7 activity through GAGs in the presence of non-saturating agonists concentrations was evident with the endogenous expression of the receptor in CHO cells. The presence of GAGs on the surface of CHO cells greatly increased the sensitivity to adenosine 5'-triphosphate and changed the main P2X7 receptor kinetic parameters EC50, Hill coefficient and E max. GAGs decreased the allosteric inhibition of P2X7 receptor through Mg(2+). GAGs activated P2X7 receptor-mediated cytoplasmic Ca(2+) influx and pore formation. Consequently, wild-type CHO-K1 cells were 2.5 fold more sensitive to cell death induced through P2X7 agonists than mutant CHO 745 cells defective in GAGs biosynthesis. In the present study, we provide the first evidence that the P2X7 receptor interacts with CD44 on the CHO-K1 cell surface. Thus, these data demonstrated that GAGs positively modulate the P2X7 receptor, and sCD44 is a part of a regulatory positive feedback loop linking P2X7 receptor activation for the intracellular response mediated through P2X7 receptor stimulation. PMID- 27551443 TI - Rap1-mediated nuclear factor-kappaB (NF-kappaB) activity regulates the paracrine capacity of mesenchymal stem cells in heart repair following infarction. AB - Paracrine effect is the major mechanism that underlies mesenchymal stem cells (MSC)-based therapy. This study aimed to examine how Rap1, telomeric repeat binding factor 2-interacting protein 1 (Terf2IP), which is a novel modulator involved in the nuclear factor-kappaB (NF-kappaB) pathway, regulates the paracrine effects of MSC-mediated heart repair following infarction. NF-kappaB activity of stromal cells was increased by Rap1 as measured by pNF-kappaB luciferase reporter activity, and this was abolished by IkB-dominant-negative protein. Knockdown of Rap1 with shRap1 resulted in diminished translocation of p65-NF-kappaB from the cytoplasm to nuclei in response to tumor necrosis factor alpha (TNF-alpha) stimulation. Compared with BM-MSCs, Rap1(-/-)-BM-MSCs displayed a significantly reduced ratio of phosphorylated NF-kappaB to NF-kappaB-p65 and of Bax to Bcl-2, and increased resistance to hypoxia-induced apoptosis by the terminal deoxynucleotidal transferase-mediated dUTP nick end labeling (TUNEL) assay. In contrast, re-expression of Rap1 in Rap1(-/-)-BM-MSCs resulted in loss of resistance to apoptosis in the presence of hypoxia. Moreover, absence of Rap1 in BM-MSCs led to downregulation of NF-kappaB activity accompanied by reduced pro inflammatory paracrine cytokines TNF-alpha, IL (interleukin)-6 and monocyte chemotactic protein-1 in Rap1(-/-)-BM-MSCs compared with BM-MSCs. The apoptosis of neonatal cardiomyocytes (NCMCs) induced by hypoxia was significantly reduced when cocultured with Rap1(-/-)-BM-MSC hypoxic-conditioned medium (CdM). The increased cardioprotective effects of Rap1(-/-)-BM-MSCs were reduced when Rap1(-/ )-BM-MSCs were reconstituted with Rap1 re-expression. Furthermore, in vivo study showed that transplantation of Rap1(-/-)-BM-MSCs significantly improved heart function, decreased infarct size, prevented cardiomyocyte apoptosis and inhibited inflammation compared with controls and BM-MSCs (P<0.01). This study reveals that Rap1 has a critical role in the regulation of MSC paracrine actions. Compared with BM-MSCs, Rap1(-/-)-BM-MSCs decreased NF-kappaB sensitivity to stress-induced pro-inflammatory cytokine production and reduced apoptosis. Selective inhibition of Rap1 in BM-MSCs may be a novel strategy to enhance MSC-based therapeutic efficacy in myocardial infarction. PMID- 27551444 TI - Characterization of GSK'963: a structurally distinct, potent and selective inhibitor of RIP1 kinase. AB - Necroptosis and signaling regulated by RIP1 kinase activity is emerging as a key driver of inflammation in a variety of disease settings. A significant amount has been learned about how RIP1 regulates necrotic cell death through the use of the RIP1 kinase inhibitor Necrostatin-1 (Nec-1). Nec-1 has been a transformational tool for exploring the function of RIP1 kinase activity; however, its utility is somewhat limited by moderate potency, off-target activity against indoleamine-2,3 dioxygenase (IDO), and poor pharmacokinetic properties. These limitations of Nec 1 have driven an effort to identify next-generation tools to study RIP1 function, and have led to the identification of 7-Cl-O-Nec-1 (Nec-1s), which has improved pharmacokinetic properties and lacks IDO inhibitory activity. Here we describe the characterization of GSK'963, a chiral small-molecule inhibitor of RIP1 kinase that is chemically distinct from both Nec-1 and Nec-1s. GSK'963 is significantly more potent than Nec-1 in both biochemical and cellular assays, inhibiting RIP1 dependent cell death with an IC50 of between 1 and 4 nM in human and murine cells. GSK'963 is >10 000-fold selective for RIP1 over 339 other kinases, lacks measurable activity against IDO and has an inactive enantiomer, GSK'962, which can be used to confirm on-target effects. The increased in vitro potency of GSK'963 also translates in vivo, where GSK'963 provides much greater protection from hypothermia at matched doses to Nec-1, in a model of TNF-induced sterile shock. Together, we believe GSK'963 represents a next-generation tool for examining the function of RIP1 in vitro and in vivo, and should help to clarify our current understanding of the role of RIP1 in contributing to disease pathogenesis. PMID- 27551445 TI - Silencing of RUNX2 enhances gemcitabine sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the stimulation of TAp63-mediated cell death. AB - Runt-related transcription factor 2 (RUNX2) has been considered to be one of master regulators for osteoblast differentiation and bone formation. Recently, we have described that RUNX2 attenuates p53/TAp73-dependent cell death of human osteosarcoma U2OS cells bearing wild-type p53 in response to adriamycin. In this study, we have asked whether RUNX2 silencing could enhance gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells. Under our experimental conditions, GEM treatment increased the expression level of p53 family TAp63, whereas RUNX2 was reduced following GEM exposure, indicating that there exists an inverse relationship between the expression level of TAp63 and RUNX2 following GEM exposure. To assess whether TAp63 could be involved in the regulation of GEM sensitivity of AsPC-1 cells, small interfering RNA-mediated knockdown of TAp63 was performed. As expected, silencing of TAp63 significantly prohibited GEM-dependent cell death as compared with GEM-treated non-silencing cells. As TAp63 was negatively regulated by RUNX2, we sought to examine whether RUNX2 knockdown could enhance the sensitivity to GEM. Expression analysis demonstrated that depletion of RUNX2 apparently stimulates the expression of TAp63, as well as proteolytic cleavage of poly ADP ribose polymerase (PARP) after GEM exposure, and further augmented GEM-mediated induction of p53/TAp63-target genes, such as p21 (WAF1) , PUMA and NOXA, relative to GEM-treated control transfected cells, implying that RUNX2 has a critical role in the regulation of GEM resistance through the downregulation of TAp63. Notably, ablation of TAp63 gave a decrease in number of gammaH2AX-positive cells in response to GEM relative to control-transfected cells following GEM exposure. Consistently, GEM-dependent phosphorylation of ataxia telangiectasia-mutated protein was remarkably impaired in TAp63 knockdown cells. Collectively, our present findings strongly suggest that RUNX2-mediated repression of TAp63 contributes at least in part to GEM resistance of AsPC-1 cells, and thus silencing of RUNX2 may be a novel strategy to enhance the efficacy of GEM in p53-deficient pancreatic cancer cells. PMID- 27551446 TI - Modulation of dendritic cell function by the radiation-mediated secretory protein gamma-synuclein. AB - Recently, gamma-synuclein (SNCG), which is also known as breast cancer-specific gene-1, has been demonstrated to be an adverse and aggressive marker in breast cancer. In our previous study, SNCG was significantly upregulated in irradiated human breast cancer cells. The aim of this study was to investigate whether radiation-induced, tumor-derived SNCG can influence dendritic cell (DC) function in immune systems. The phenotypical and functional changes of DCs in the presence or absence of SNCG were investigated by FACS analysis, ELISA, and real-time PCR. The ability of SNCG-treated DCs to influence T cells was also examined by coculturing with T cells. The treatment of DCs with SNCG protein inhibited the surface expression of the co-stimulatory molecules CD40 and CD86, and decreased the mRNA levels of pro-inflammatory cytokines. The SNCG-treated DCs inhibited T cell proliferation slightly, but distinctively increased the population of regulatory T cells. In addition, the production of TGF-beta from T cells was significantly increased when they were cocultured with SNCG-treated DCs. Taken together, these results demonstrate that tumor-derived SNCG contributes to immunosuppressive effects via the inhibition of DC differentiation and activation, thus making it a potential target for cancer treatment. PMID- 27551447 TI - Stereospecific induction of apoptosis in tumor cells via endogenous C16-ceramide and distinct transcripts. AB - Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In this study, we show here that the elevation of endogenous C16 ceramide levels is a common feature of several known apoptosis-inducing triggers like mmLDL, TNF-alpha, H2O2 and exogenous C6-ceramide. Vice versa apoptosis requires elevation of endogenous C16-ceramide levels in cells. Enantiomers of a synthetic ceramide analog HPL-1RS36N have been developed as probes and vary in their capacity to inducing apoptosis in macrophages and HT-29 cells. Apoptosis induction by the two synthetic ceramide analogs HPL-39N and HPL-1R36N correlates with generation of cellular C16-ceramide concentration. In contrast to the S enantiomer HPL-1S36N, the R-enantiomer HPL-1R36N shows significant effects on the expression of distinct genes known to be involved in cell cycle, cell growth and cell death (CXCL10, CCL5 and TNF-alpha), similarly on apoptosis induction. Enantioselective effects on transcription induced by metabolically stable synthetic probes provide clues on molecular mechanisms of ceramide-induced signaling, as well as leads for future anti-cancer agents. PMID- 27551448 TI - Muscle LIM protein/CSRP3: a mechanosensor with a role in autophagy. AB - Muscle LIM protein (MLP) is a microtubule-associated protein expressed in cardiac and muscle tissues that belongs to the cysteine-rich protein (CSRP/CRP) family. MLP has a central role during muscle development and for architectural maintenance of muscle cells. However, muscle cells rely on autophagy during differentiation and for structural maintenance. To study the role of MLP in autophagy, we have used C2C12 mouse myoblasts silenced or overexpressing MLP. Our results show that MLP contributes to the correct autophagosome formation and flux by interacting with LC3 as demonstrated by co-immunoprecipitation and PLA assay. In fact, MLP silencing results in decreased LC3-II staining and absent degradation of long-lived proteins. Moreover, MLP silencing impaired myoblasts differentiation as measured by decreased expression of MyoD1, MyoG1 and myosin heavy chain. Ultrastructural analysis revealed the presence of large empty autophagosomes in myoblasts and multimembranous structures in myotubes from MLP silenced clones. Impaired autophagy in MLP-silenced cells resulted in increased susceptibility to apoptotic cell death. In fact, treatment of MLP-silenced C2C12 myoblasts and myotubes with staurosporine resulted in increased caspase-3 and PARP cleavage as well as increased percentage of cell death. In conclusion, we propose that MLP regulates autophagy during muscle cell differentiation or maintenance through a mechanism involving MLP/LC3-II interaction and correct autophagosome formation. PMID- 27551449 TI - Involvement of inhibitory PAS domain protein in neuronal cell death in Parkinson's disease. AB - Inhibitory PAS domain protein (IPAS), a repressor of hypoxia-inducible factor dependent transcription under hypoxia, was found to exert pro-apoptotic activity in oxidative stress-induced cell death. However, physiological and pathological processes associated with this activity are not known. Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. Activation of the PINK1-Parkin pathway attenuated IPAS-dependent apoptosis. IPAS was markedly induced in the midbrain following 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) administration, and IPAS-deficient mice showed resistance to MPTP-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). A significant increase in IPAS expression was found in SNpc neurons in patients with sporadic PD. These results indicate a mechanism of neurodegeneration in PD. PMID- 27551450 TI - mTORC2 controls cancer cell survival by modulating gluconeogenesis. AB - For rapid tumor growth, cancer cells often reprogram the cellular metabolic processes to obtain enhanced anabolic precursors and energy. The molecular changes of such metabolic rewiring are far from established. Here we explored the role of mTOR (mechanistic target of rapamycin), which serves as a key regulator of cell growth, proliferation and survival, in the metabolic reprograming of cancer cells. When we inhibited mTOR in human hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) cells, using pharmacologic inhibitors or by RNA interference, we noticed shuttle of the glycolytic flux to gluconeogenesis pathway along with reduction in cellular proliferation and survival. Augmentation of gluconeogenesis was mechanistically linked to upregulation of the key gluconeogenic enzymes PCK1 and G6PC expressions, enhanced lactate dehydrogenase activity and glucose-derived lipogenesis without causing any attenuation in mitochondrial function. Interestingly, concomitant knocking down of PCK1 and not G6PC along with mTOR pathway could overcome the inhibition of cancer cell proliferation and survival. These observations were validated by identifying distinctive diminution of PCK1 and G6PC expressions in human HCC and RCC transcriptome data. Significant correlation between mTOR-dependent upregulation of PCK1 and cell death in different cancer cell lines further emphasizes the physiological relevance of this pathway. We reveal for the first time that inhibition of mTORC2 and consequent redistribution of glycolytic flux can have a prosurvival role in HCC and RCC cancer cells only in the presence of downregulation of gluconeogenesis pathway genes, thus identifying novel pivots of cancer cell metabolic rewiring and targets for therapy. PMID- 27551451 TI - Curcumin induces crosstalk between autophagy and apoptosis mediated by calcium release from the endoplasmic reticulum, lysosomal destabilization and mitochondrial events. AB - Curcumin, a major active component of turmeric (Curcuma longa, L.), has anticancer effects. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying these effects is still unclear. Here, we investigated the mechanisms leading to apoptosis in curcumin-treated cells. Curcumin induced endoplasmic reticulum stress causing calcium release, with a destabilization of the mitochondrial compartment resulting in apoptosis. These events were also associated with lysosomal membrane permeabilization and of caspase-8 activation, mediated by cathepsins and calpains, leading to Bid cleavage. Truncated tBid disrupts mitochondrial homeostasis and enhance apoptosis. We followed the induction of autophagy, marked by the formation of autophagosomes, by staining with acridine orange in cells exposed curcumin. At this concentration, only the early events of apoptosis (initial mitochondrial destabilization with any other manifestations) were detectable. Western blotting demonstrated the conversion of LC3-I to LC3-II (light chain 3), a marker of active autophagosome formation. We also found that the production of reactive oxygen species and formation of autophagosomes following curcumin treatment was almost completely blocked by N-acetylcystein, the mitochondrial specific antioxidants MitoQ10 and SKQ1, the calcium chelators, EGTA-AM or BAPTA-AM, and the mitochondrial calcium uniporter inhibitor, ruthenium red. Curcumin-induced autophagy failed to rescue all cells and most cells underwent type II cell death following the initial autophagic processes. All together, these data imply a fail-secure mechanism regulated by autophagy in the action of curcumin, suggesting a therapeutic potential for curcumin. Offering a novel and effective strategy for the treatment of malignant cells. PMID- 27551452 TI - Pro-survival function of MEF2 in cardiomyocytes is enhanced by beta-blockers. AB - beta1-Adrenergic receptor (beta1-AR) stimulation increases apoptosis in cardiomyocytes through activation of cAMP/protein kinase A (PKA) signaling. The myocyte enhancer factor 2 (MEF2) proteins function as important regulators of myocardial gene expression. Previously, we reported that PKA signaling directly represses MEF2 activity. We determined whether (a) MEF2 has a pro-survival function in cardiomyocytes, and (b) whether beta-adrenergic/PKA signaling modulates MEF2 function in cardiomyocytes. Initially, we observed that siRNA mediated gene silencing of MEF2 induces cardiomyocyte apoptosis as indicated by flow cytometry. beta1-AR activation by isoproterenol represses MEF2 activity and promotes apoptosis in cultured neonatal cardiomyocytes. Importantly, beta1-AR mediated apoptosis was abrogated in cardiomyocytes expressing a PKA-resistant form of MEF2D (S121/190A). We also observed that a beta1-blocker, Atenolol, antagonizes isoproterenol-induced apoptosis while concomitantly enhancing MEF2 transcriptional activity. beta-AR stimulation modulated MEF2 cellular localization in cardiomyocytes and this effect was reversed by beta-blocker treatment. Furthermore, Kruppel-like factor 6, a MEF2 target gene in the heart, functions as a downstream pro-survival factor in cardiomyocytes. Collectively, these data indicate that (a) MEF2 has an important pro-survival role in cardiomyocytes, and (b) beta-adrenergic signaling antagonizes the pro-survival function of MEF2 in cardiomyocytes and beta-blockers promote it. These observations have important clinical implications that may contribute to novel strategies for preventing cardiomyocyte apoptosis associated with heart pathology. PMID- 27551453 TI - Exposure to Endosulfan can result in male infertility due to testicular atrophy and reduced sperm count. AB - Endosulfan (ES) is a widely used organochlorine pesticide and is speculated to be detrimental to human health. However, very little is known about mechanism of its genotoxicity. Using mouse model system, we show that exposure to ES affected physiology and cellular architecture of organs and tissues. Among all organs, damage to testes was extensive and it resulted in death of different testicular cell populations. We find that the damage in testes resulted in qualitative and quantitative defects during spermatogenesis in a time-dependent manner, increasing epididymal reactive oxygen species levels, affecting sperm chromatin integrity. This further culminated in reduced number of epididymal sperms and actively motile sperms. Finally, we show that ES exposure affected fertility in male but not in female mice. Therefore, we demonstrate that ES exerts pathophysiological changes in mice, induces testicular atrophy, affects spermatogenesis, reduces quantity and vigour of epididymal sperm and leads to infertility in males. PMID- 27551454 TI - Tumor suppressor Nf2/merlin drives Schwann cell changes following electromagnetic field exposure through Hippo-dependent mechanisms. AB - Previous evidence showed mutations of the neurofibromin type 2 gene (Nf2), encoding the tumor suppressor protein merlin, in sporadic and vestibular schwannomas affecting Schwann cells (SCs). Accordingly, efforts have been addressed to identify possible factors, even environmental, that may regulate neurofibromas growth. In this context, we investigated the exposure of SC to an electromagnetic field (EMF), which is an environmental issue modulating biological processes. Here, we show that SC exposed to 50 Hz EMFs changes their morphology, proliferation, migration and myelinating capability. In these cells, merlin is downregulated, leading to activation of two intracellular signaling pathways, ERK/AKT and Hippo. Interestingly, SC changes their phenotype toward a proliferative/migrating state, which in principle may be pathologically relevant for schwannoma development. PMID- 27551455 TI - Caspase-independent apoptosis in infected macrophages triggered by sulforaphane via Nrf2/p38 signaling pathways. AB - Mycobacterium abscessus (Mabs), a non-tuberculous mycobacterium, is an emerging and rapidly growing opportunistic pathogen that is frequently found in patients with cystic fibrosis and in immunosuppressed patients. Its high tolerance to antibiotics is of great concern for public health. In this study, our results showed that human THP-1-derived macrophages infected with M. abscessus presented an increase in ROS production and cell necrosis. In addition, M. abscessus infection triggered activation of the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and the induction of HO-1 and NQO1 expression levels. Interestingly, pretreatment of macrophages with sulforaphane (SFN), an activator of the antioxidant key regulator Nrf2, followed by M. abscessus infection significantly decreased mycobacterial burden. We demonstrated that this reduction in mycobacterial growth was due to an activation in cell apoptosis in SFN pretreated and M. abscessus-infected macrophages. Pretreatment with specific MAPK inhibitors, PD98059, SP600125, and SB203580 to ERK, JNK, and p38 respectively, failed to inhibit induction of Nrf2 expression, suggesting that Nrf2 signaling pathway was upstream of MAPK signaling. Activation of cell apoptosis was caspase 3/7 independent but p38 MAPK dependent. Moreover, p38 MAPK induction was abolished in macrophages transfected with Nrf2 siRNA. In addition, p38 inhibitor abolished Nrf2-dependent apoptosis in infected macrophages. Taken together, our results indicate that modulation of the Nrf2 signaling using Nrf2 activators may help potentiate the actual drug therapies used to treat mycobacterial infection. PMID- 27551456 TI - The p53 co-activator Zac1 neither induces cell cycle arrest nor apoptosis in chicken Lim1 horizontal progenitor cells. AB - Chicken horizontal progenitor cells are able to enter their final mitosis even in the presence of DNA damage despite having a functional p53-p21 system. This suggests that they are resistant to DNA damage and that the regulation of the final cell cycle of horizontal progenitor cells is independent of the p53-p21 system. The activity of p53 is regulated by positive and negative modulators, including the zinc finger containing transcription factor Zac1 (zinc finger protein that regulates apoptosis and cell cycle arrest). Zac1 interacts with and enhances the activity of p53, thereby inducing cell cycle arrest and apoptosis. In this work, we use a gain-of-function assay in which mouse Zac1 (mZac1) is overexpressed in chicken retinal progenitor cells to study the effect on the final cell cycle of horizontal progenitor cells. The results showed that overexpression of mZac1 induced expression of p21 in a p53-dependent way and arrested the cell cycle as well as triggered apoptosis in chicken non-horizontal retinal progenitor cells. The negative regulation of the cell cycle by mZac1 is consistent with its proposed role as a tumour-suppressor gene. However, the horizontal cells were not affected by mZac1 overexpression. They progressed into S- and late G2/M-phase despite overexpression of mZac1. The inability of mZac1 to arrest the cell cycle in horizontal progenitor cells support the notion that the horizontal cells are less sensitive to events that triggers the p53 system during their terminal and neurogenic cell cycle, compared with other retinal cells. These properties are associated with a cell that has a propensity to become neoplastic and thus with a cell that may develop retinoblastoma. PMID- 27551457 TI - Local anesthetics induce autophagy in young permanent tooth pulp cells. AB - Pulp cells are essential for tooth development, and dentin repair and regeneration. In addition these cells have been identified as an important stem cell source. Local anesthetics are widely used in dental clinics, as well as the other clinical disciplines and have been suggested to interfere with human permanent tooth development and induce tooth agenesis through unknown mechanisms. Using pig model and human young permanent tooth pulp cells, our research has identified that the local anesthetics commonly used in clinics can affect cell proliferation. Molecular pathway profiling suggested that LC3II is one of the earliest molecules induced by the agents and p62 is the only common downstream target identified for all the drugs tested. The effect of the drugs could be partially recovered by V-ATPase inhibitor only if early intervention is performed. Our results provide novel evidence that local anesthetics could affect tooth cell growth that potentially can have impacts on tooth development. PMID- 27551458 TI - Heme-based catalytic properties of human serum albumin. AB - Human serum albumin (HSA): (i) controls the plasma oncotic pressure, (ii) modulates fluid distribution between the body compartments, (iii) represents the depot and carrier of endogenous and exogenous compounds, (iv) increases the apparent solubility and lifetime of hydrophobic compounds, (v) affects pharmacokinetics of many drugs, (vi) inactivates toxic compounds, (vii) induces chemical modifications of some ligands, (viii) displays antioxidant properties, and (ix) shows enzymatic properties. Under physiological and pathological conditions, HSA has a pivotal role in heme scavenging transferring the metal macrocycle from high- and low-density lipoproteins to hemopexin, thus acquiring globin-like reactivity. Here, the heme-based catalytic properties of HSA are reviewed and the structural bases of drug-dependent allosteric regulation are highlighted. PMID- 27551460 TI - Cytotoxic activity of the MK2 inhibitor CMPD1 in glioblastoma cells is independent of MK2. AB - MAPK-activated protein kinase 2 (MK2) is a checkpoint kinase involved in the DNA damage response. MK2 inhibition enhances the efficacy of chemotherapeutic agents; however, whether MK2 inhibition alone, without concurrent chemotherapy, would attenuate survival of cancer cells has not been investigated. CMPD1 is a widely used non-ATP competitive inhibitor that prevents MK2 phosphorylation. We employed CMPD1 together with MK2 knock-down and ATP-competitive MK2 inhibitor III (MK2i) in a panel of glioblastoma cells to assess whether MK2 inhibition could induce cancer cell death. While CMPD1 was effective at selective killing of cancer cells, MK2i and MK2 knock-down had no effect on viability of glioblastoma cells. CMPD1 treatment induced a significant G2/M arrest but MK2i-treated cells were only minimally arrested at G1 phase. Intriguingly, at doses that were cytotoxic to glioblastoma cells, CMPD1 did not inhibit phosphorylation of MK2 and of its downstream substrate Hsp27. These results suggest that CMPD1 exhibits cytotoxic activity independently of MK2 inhibition. Indeed, we identified tubulin as a primary target of the CMPD1 cytotoxic activity. This study demonstrates how functional and mechanistic studies with appropriate selection of test compounds, combining genetic knock-down and pharmacological inhibition, coordinating timing and dose levels enabled us to uncover the primary target of an MK2 inhibitor commonly used in the research community. Tubulin is emerging as one of the most common non-kinase targets for kinase inhibitors and we propose that potential tubulin-targeting activity should be assessed in preclinical pharmacology studies of all novel kinase inhibitors. PMID- 27551459 TI - Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease. AB - Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18 kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and NeuN (antigen known as 'neuronal nuclei', also known as Rbfox3) expression. As part of the neurodifferentiation process, they can amplify cell death induced by glutamate. Interestingly, the compound 2 phenylquinazolin-4-yl dimethylcarbamate (MGV-1) can induce expansive neurite sprouting on its own and also in synergy with nerve growth factor and with glutamate. Glycine is not required, indicating that N-methyl-D-aspartate receptors are not involved in this activity. These diverse effects on cells of glial origin and on cells with neuronal characteristics induced in culture by this one compound, MGV-1, as reported in this article, mimic the diverse events that take place during embryonic development of the brain (maintenance of glial integrity, differentiation of progenitor cells to mature neurons, and weeding out of non-differentiating progenitor cells). Such mechanisms are also important for protective, curative, and restorative processes that occur during and after brain injury and brain disease. Indeed, we found in a rat model of systemic kainic acid injection that MGV-1 can prevent seizures, counteract the process of ongoing brain damage, including edema, and restore behavior defects to normal patterns. Furthermore, in the R6-2 (transgenic mouse model for Huntington disease; Strain name: B6CBA-Tg(HDexon1)62Gpb/3J) transgenic mouse model for Huntington disease, derivatives of MGV-1 can increase lifespan by >20% and reduce incidence of abnormal movements. Also in vitro, these derivatives were more effective than MGV 1. PMID- 27551461 TI - ALS-associated mutant FUS inhibits macroautophagy which is restored by overexpression of Rab1. AB - Amyotrophic lateral sclerosis (ALS) is characterised by the formation of intracellular misfolded protein inclusions that form in motor neurons. Autophagy is the major degradation pathway for aggregate-prone proteins within lysosomes. Autophagy begins by the production of the omegasome, forming the autophagosome membrane, which then fuses with the lysosome. Mutations in fused in sarcoma (FUS) cause 5% of familial ALS cases and FUS-positive inclusions are also formed in sporadic ALS tissues. In this study, we demonstrate that the expression of ALS associated mutant FUS impairs autophagy in neuronal cells. In mutant FUS expressing neuronal cells, accumulation of ubiquitinated proteins and autophagy substrates p62 and NBR1 was detected, and formation of both the omegasome and autophagosome was inhibited in these cells. However, overexpression of Rab1 rescued these defects, suggesting that Rab1 is protective in ALS. The number of LC3-positive vesicles was also increased in motor neurons from the spinal cord of an ALS patient carrying a FUS (R521C) mutation compared with a control patient, providing additional evidence that autophagy is dysregulated in mutant FUS associated ALS. This study provides further understanding of the intricate autophagy system and neurodegeneration in ALS. PMID- 27551462 TI - The interplay of autophagy and beta-Catenin signaling regulates differentiation in acute myeloid leukemia. AB - The major feature of leukemic cells is an arrest of differentiation accompanied by highly active proliferation. In many subtypes of acute myeloid leukemia, these features are mediated by the aberrant Wnt/beta-Catenin pathway. In our study, we established the lectin LecB as inducer of the differentiation of the acute myeloid leukemia cell line THP-1 and used it for the investigation of the involved processes. During differentiation, functional autophagy and low beta Catenin levels were essential. Corresponding to this, a high beta-Catenin level stabilized proliferation and inhibited autophagy, resulting in low differentiation ability. Initiated by LecB, beta-Catenin was degraded, autophagy became active and differentiation took place within hours. Remarkably, the reduction of beta-Catenin sensitized THP-1 cells to the autophagy-stimulating mTOR inhibitors. As downmodulation of E-Cadherin was sufficient to significantly reduce LecB-mediated differentiation, we propose E-Cadherin as a crucial interaction partner in this signaling pathway. Upon LecB treatment, E-Cadherin colocalized with beta-Catenin and thereby prevented the induction of beta-Catenin target protein expression and proliferation. That way, our study provides for the first time a link between E-Cadherin, the aberrant Wnt/beta-Catenin signaling, autophagy and differentiation in acute myeloid leukemia. Importantly, LecB was a valuable tool to elucidate the underlying molecular mechanisms of acute myeloid leukemia pathogenesis and may help to identify novel therapy approaches. PMID- 27551463 TI - SAG-UPS attenuates proapoptotic SARM and Noxa to confer survival advantage to early hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a deadly cancer because of its commonly late diagnosis and limited treatment options. SAG (sensitive to apoptosis gene) dependent UPS (ubiquitin-proteasome system) is a key switch between immune mediated apoptosis and overactivation-mediated protumorigenesis, prompting us to hypothesize that SAG-UPS modulates chronic inflammation-induced tumorigenesis. Here, we investigated the molecular mechanism by which SAG-UPS regulates death/survival of liver cancer cells. By retrospective studies, we found reciprocal expressions of anti-/proapoptotic factors: SAG/SARM and SAG/Noxa in human primary HCC tissues - the antiapoptotic SAG was significantly upregulated whereas the proapoptotic SARM and Noxa were markedly downregulated, suggesting their involvement in hepatocarcinogenesis. Upregulated SAG-UPS effectively manipulates the levels of high-molecular-weight ubiquitinated SARM and Noxa in carcinoma tissues compared with corresponding normal tissues. SAG-overexpressing HCC cell lines display reduced SARM and Noxa (but not Bcl-2, Bax and Bcl-xL), suggesting that SARM and Noxa are specific substrates of SAG-dependent ubiquitination. SARM overexpression activated caspase-3 and caspase-9, reducing cell viability. SAG knockdown significantly elevated apoptosis with increased cytosolic cytochrome c, confirming SAG-mediated antiapoptosis in HCC. SAG overexpression stimulated protumorigenic cytokines, IL-1beta, IL-6 and TNF, but not antitumorigenic IL-12p40 and anti-inflammatory IL-10. This is consistent with higher proinflammatory cytokines (IL-1beta, IL-6 and TNF) in hepatoma compared with healthy tissues. Altogether, early stage-upregulated SAG-UPS exacerbates hepatocarcinogenesis progression, through: (1) ubiquitination-mediated degradation of proapoptotic SARM and Noxa; and (2) production of protumorigenic cytokines that induce a protumorigenic microenvironment, conferring survival advantage to HCC cells. Thus, we propose SAG-UPS to be an early diagnostic marker for HCC, and a potential target for therapeutics development. PMID- 27551465 TI - The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-alpha to activate apoptosis. AB - Predicting and understanding the mechanism of drug-induced toxicity is one of the primary goals of drug development. It has been hypothesized that inflammation may have a synergistic role in this process. Cell-based models provide an easily manipulated system to investigate this type of drug toxicity. Several groups have attempted to reproduce in vivo toxicity with combination treatment of pharmacological agents and inflammatory cytokines. Through this approach, synergistic cytotoxicity between the investigational agent pevonedistat (MLN4924) and TNF-alpha was identified. Pevonedistat is an inhibitor of the NEDD8 activating enzyme (NAE). Inhibition of NAE prevents activation of cullin-RING ligases, which are critical for proteasome-mediated protein degradation. TNF alpha is a cytokine that is involved in inflammatory responses and cell death, among other biological functions. Treatment of cultured cells with the combination of pevonedistat and TNF-alpha, but not as single agents, resulted in rapid cell death. This cell death was determined to be mediated by caspase-8. Interestingly, the combination treatment of pevonedistat and TNF-alpha also caused an accumulation of the p10 protease subunit of caspase-8 that was not observed with cytotoxic doses of TNF-alpha. Under conditions where apoptosis was blocked, the mechanism of death switched to necroptosis. Trimerized MLKL was verified as a biomarker of necroptotic cell death. The synergistic toxicity of pevonedistat and elevated TNF-alpha was also demonstrated by in vivo rat studies. Only the combination treatment resulted in elevated serum markers of liver damage and single-cell hepatocyte necrosis. Taken together, the results of this work have characterized a novel synergistic toxicity driven by pevonedistat and TNF alpha. PMID- 27551464 TI - Novel beta-carbolines against colorectal cancer cell growth via inhibition of Wnt/beta-catenin signaling. AB - Wnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer (CRC), because of mutations in the genes encoding adenomatous polyposis coli (APC), beta-catenin and Axin. Small-molecule antagonists of Wnt/beta-catenin signaling are attractive candidates for developing effective therapeutics for CRC. In this study, we have identified a novel Wnt signaling inhibitor, isopropyl 9-ethyl-1- (naphthalen-1-yl)-9H pyrido[3,4-b]indole-3- carboxylate (Z86). Z86 inhibited Wnt reporter activities and the expression of endogenous Wnt signaling target genes in mammalian cells and antagonized the second axis formation of Xenopus embryos induced by Wnt8. We showed that Z86 treatment inhibits GSK3beta (Ser9) phosphorylation, leading to its overactivation and promoting the phosphorylation and degradation of beta catenin. In vitro, Z86 selectively inhibited the growth of CRC cells with constitutive Wnt signaling and caused obvious G1-phase arrest of the cell cycle. Notably, in a nude mouse model, Z86 inhibited dramatically the xenografted tumor growth of CRC. Daily intraperitoneal injection of Z86 at 5 mg/kg resulted in >70% reduction in the tumor weight of HCT116 cell origin that was associated with decreased GSK3beta (Ser9) phosphorylation and increased beta-catenin phosphorylation. Taken together, our findings provide a novel promising chemotype for CRC therapeutics development targeting the canonical Wnt signaling. PMID- 27551466 TI - Helicobacter pylori VacA induces apoptosis by accumulation of connexin 43 in autophagic vesicles via a Rac1/ERK-dependent pathway. AB - Helicobacter pylori (H. pylori) produces vacuolating cytotoxin (VacA), a potent protein toxin, which is associated with gastric inflammation and ulceration. Recent studies demonstrated that connexins (Cxs), which are responsible for intracellular communication at gap junctions (GJs) as well as cell homeostasis, participate in VacA-induced cell death. We now demonstrate in AZ-521 cells that VacA increased cytoplasmic Cx43, accompanied by LC3-II generation in a time- and dose-dependent manner without induction of Cx43 mRNA expression. Inhibition of VacA-induced Rac1 activity prevented ERK phosphorylation and the increase in Cx43. Suppression of ERK activity and addition of N-acetyl-cysteine inhibited VacA-dependent increase in Cx43 and LC3-II. DIDS, an anion-selective inhibitor, suppressed VacA-dependent increase in Cx43, suggesting that VacA channel activity was involved in this pathway. By confocal microscopy, Cx43 increased by VacA was predominately localized in cholesterol-rich, detergent-resistant membranes including GJs, and a fraction of Cx43 was incorporated in endocytotic vesicles and autophagolysosomes. Accumulation of Cx43 was also observed in gastric mucosa from H. pylori-infected patients compared with healthy controls, suggesting that the pathogen caused a similar effect in vivo. Our findings show that VacA mediated effects on autophagy inhibits turnover of Cx43, resulting in increased levels in the cytoplasm, leading eventually to apoptotic cell death. PMID- 27551467 TI - DIDS (4,4'-Diisothiocyanatostilbene-2,2'-disulfonate) directly inhibits caspase activity in HeLa cell lysates. AB - Apoptosis is an important mechanism of cell demise in multicellular organisms and Cl(-) transport has an important role in the progression of the apoptotic volume decrease (AVD). DIDS (4,4'-Diisothiocyanatostilbene-2,2'-disulfonate) is one of the most commonly used Cl(-) transport inhibitors that eliminates or reduces different apoptotic hallmarks such as AVD, caspase-3 activity and DNA fragmentation. DIDS is also a protein crosslinker that alkylates either amino or thiol groups. Since caspases are thiol proteases, our aim was to study whether DIDS could directly inhibit the activity of these proteases. Here, we show that caspase activity induced by 4 h incubation with staurosporine was inhibited by DIDS in HeLa cells that were maintained in the absence of serum for 24 h. Interestingly, the caspase-inhibitory effect of DIDS is downstream to the inhibition of cytochrome c release, suggesting that DIDS might be also acting at the apoptosome. Moreover, DIDS was able to inhibit capase-3, -9, and -8 activities in cell lysates, implying that DIDS can react with and directly block caspases. Our data suggest that antiapoptotic activity of DIDS involves not only inhibition of the voltage-dependent anion channel (VDAC) at the mitochondria and Cl(-) channels at the plasma membrane, but also a third mechanism based on the direct inhibition of caspases. PMID- 27551468 TI - PPARgamma regulated CIDEA affects pro-apoptotic responses in glioblastoma. AB - Refractoriness of glioblastoma multiforme (GBM) to current treatment paradigms has necessitated identification of new targets to better the existing therapeutic strategies. One such target is peroxisome proliferator-activated receptor gamma (PPARgamma) - a transcription factor involved in regulation of lipid metabolism and inflammation. Expression of PPARgamma, a known regulator of cell death inducing DFFA-like effector (CIDEA), is modulated by hypoxia inducible factor (HIF-1alpha). While the involvement of CIDEA in lipid metabolism is known, its role in malignancies remains largely unknown. An elevated PPARgamma and low CIDEA level was observed in GBM tumors as compared with surrounding non-neoplastic tissue. As reciprocal relation exists between PPAR and HIF-1alpha: and as HIF 1alpha is a key component in glioma progression, their role in regulating CIDEA expression in glioblastoma was investigated. Although HIF-1alpha inhibition had no effect on CIDEA expression, pharmacological inhibition of PPARgamma elevated CIDEA levels. PPARgamma mediated upregulation of CIDEA was accompanied by decreased recruitment of NFkappaB and SP1 to their predicted binding sites on CIDEA promoter. Ectopic expression of CIDEA triggered apoptosis, activated JNK, decreased HIF-1alpha activation and increased PPARgamma levels in glioma cells. While CIDEA overexpression induced actin cytoskeletal disruption, cell cycle arrest, release of pro-inflammatory cytokine IL-6 in a JNK-dependent manner; CIDEA mediated apoptotic cell death, decreased STAT3 phosphorylation and increased p53 acetylation was JNK independent. This study highlights for the first time the existence of (i) PPARgamma-CIDEA regulatory loop in glioma and (ii) novel function of CIDEA as regulator of glioma cell survival. PMID- 27551469 TI - Questions & Controversies. PMID- 27551470 TI - Current questions and controversies in chromosome fragile site research: does WWOX, the gene product of common fragile site FRA16D, have a passive or active role in cancer? PMID- 27551471 TI - BH3-Only protein bmf is required for the maintenance of glucose homeostasis in an in vivo model of HNF1alpha-MODY diabetes. AB - Heterozygous loss-of-function mutations in the hepatocyte nuclear factor 1alpha (HNF-1alpha) gene can lead to diminished amounts of functional HNF-1alpha, resulting in the onset of a particularly severe form of maturity-onset diabetes of the young (MODY). We have previously shown that induction of a dominant negative mutant of HNF-1alpha (DNHNF-1alpha) results in the activation of the bioenergetic stress sensor AMP-activated protein kinase (AMPK), preceding the onset of apoptosis and the induction of pro-apoptotic Bcl-2 homology domain-3 only protein Bmf (Bcl-2-modifying factor) as a mediator of DNHNF-1alpha-induced apoptosis. Through the knockout of bmf in a transgenic mouse model with DNHNF 1alpha suppression of HNF-1alpha function in pancreatic beta-cells, this study aimed to examine the effect of loss-of-function of this BH3-only protein on the disease pathology and progression, and further elucidate the role of Bmf in mediating DNHNF-1alpha-induced beta-cell loss. Morphological analysis revealed an attenuation in beta-cell loss in bmf-deficient diabetic male mice and preserved insulin content. Surprisingly, bmf deficiency was found to exacerbate hyperglycemia in both diabetic male and hyperglycemic female mice, and ultimately resulted in a decreased glucose-stimulated insulin response, implicating a role for Bmf in glucose homeostasis regulation independent of an effect on beta-cell loss. Collectively, our data demonstrate that Bmf contributes to the decline in beta-cells in a mouse model of HNF1A-MODY but is also required for the maintenance of glucose homeostasis in vivo. PMID- 27551472 TI - Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines. AB - The study aimed to assess the effects of polyphenols when used in combination with doxorubicin and etoposide, and to determine whether polyphenols sensitised leukaemia cells, causing inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. This study is based on findings in solid cancer tumours, which have shown that polyphenols can sensitize cells to chemotherapy, and induce apoptosis and/or cell-cycle arrest. This could enable a reduction of chemotherapy dose and off-target effects, whilst maintaining treatment efficacy. Quercetin, apigenin, emodin, rhein and cis-stilbene were investigated alone and in combination with etoposide and doxorubicin in two lymphoid and two myeloid leukaemia cells lines. Measurements were made of ATP levels (using CellTiter-Glo assay) as an indication of total cell number, cell cycle progression (using propidium iodide staining and flow cytometry) and apoptosis (NucView caspase 3 assay and Hoechst 33342/propidium iodide staining). Effects of combination treatments on caspases 3, 8 and 9 activity were determined using Glo luminescent assays, glutathione levels were measured using the GSH-Glo Glutathione Assay and DNA damage determined by anti-gammaH2AX staining. Doxorubicin and etoposide in combination with polyphenols synergistically reduced ATP levels, induced apoptosis and increased S and/or G2/M phase cell cycle arrest in lymphoid leukaemia cell lines. However, in the myeloid cell lines the effects of the combination treatments varied; doxorubicin had a synergistic or additive effect when combined with quercetin, apigenin, emodin, and cis-stilbene, but had an antagonistic effect when combined with rhein. Combination treatment caused a synergistic downregulation of glutathione levels and increased DNA damage, driving apoptosis via caspase 8 and 9 activation. However, in myeloid cells where antagonistic effects were observed, this was associated with increased glutathione levels and a reduction in DNA damage and apoptosis. This study has demonstrated that doxorubicin and etoposide activity were enhanced by polyphenols in lymphoid leukaemia cells, however, differential responses were seen in myeloid cells with antagonistic responses seen in some combination therapies. PMID- 27551473 TI - The H1047R point mutation in p110 alpha changes the morphology of human colon HCT116 cancer cells. AB - The class IA phosphatidylinositol 3-kinases (PI3K) is involved in controlling changes in cell morphology, which is a highly coordinated cellular event. This event is powered by actin filament polymerization and remodeling. The gain-of function mutations in the catalytic subunit of p110alpha of class IA PI3K, which occur in up to one-third of human colorectal cancers (CRCs), are capable of causing dysregulation of cell signaling and thus may result in the alteration in cell morphology and motility and in turn cause cancer metastasis. In vivo studies have demonstrated that cell lines bearing the H1047R point mutation, the most frequent cancer-specific mutation in the kinase domain of p110alpha, are more metastatic than cells carrying wild-type p110alpha. In the current study, we show that the H1047R in p110alpha of PI3K decreases F-actin polymerization, increases the formation of filopodia and significantly changes the cell morphology in HCT116 cancer cells. The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), which is also involved in actin polymerization and cell migration, is downregulated by the H1047R mutation in p110alpha. Our data suggest that the H1047R mutation in PI3K is responsible for the rearrangement of the cytoskeleton, alteration in cell morphology and enhancing cell motility, and that Bcl-2 may be involved in the H1047R mutation-mediated morphological changes and increased migratory capability. PMID- 27551474 TI - Cytosolic phospholipase A2 regulates alcohol-mediated astrocyte inflammatory responses in HIV-associated neurocognitive disorders. AB - Alcohol (EtOH) abuse and HIV-1 infection remain leading public health problems not only in the United States but also across the world. Alcohol abusers have a significantly greater risk of HIV-1 infection than non-drinkers globally. In the United States, prevalence of EtOH abuse is over two-fold higher in HIV-1-positive individuals than that of the general population. Although alcohol abusers show neurodegeneration, exacerbated neuroinflammation and oxidative damage, the mechanism(s) by which EtOH regulates astrocyte inflammatory responses in HIV associated neurocognitive disorders is unknown. Thus, we explored signaling pathway(s) involved in EtOH-mediated activation of human astrocytes with HIV-1 and subsequent alterations in their inflammatory functions. Alcohol exposure altered the morphology of astrocytes, proinflammatory responses and induced cytotoxicity in a dose-dependent manner. Time-dependent changes were also evaluated. EtOH and HIV-1 cotreatment decreased cell viability and proliferation, while increasing apoptosis and mitochondrial depolarization. EtOH and HIV-1 together increased the levels of proinflammatory molecules, interleukin-1beta, tumor necrosis factor-alpha, CXCL8, tissue inhibitor of metalloproteinases-1 and more importantly, arachidonic acid, a known downstream target of cytosolic phospholipase A2 (cPLA2). Consistent with this observation, phospho-cPLA2 levels were augmented in HIV-1 and EtOH cotreatment as compared with HIV-1 or EtOH alone. Cyclooxygenase 2 was upregulated as measured by real-time PCR and western blot, whereas cotreatment of HIV-1 and EtOH decreased cytochrome P450-2E1 levels as compared with EtOH alone. Furthermore, we confirmed that blocking cPLA2 with arachidonyl tri floro methyl ketone, a cPLA2-specific inhibitor, effectively prevented cPLA2 phosphorylation and downstream outcomes. Thus, the present findings suggest that cPLA2 has a critical role in alcohol and HIV-induced astrocyte inflammation. In the future, cPLA2 inhibitors may present novel therapeutic tools to treat alcohol abuse and HIV-associated neurocognitive disorder comorbidity. PMID- 27551475 TI - Gingival fibroblasts resist apoptosis in response to oxidative stress in a model of periodontal diseases. AB - Periodontal diseases are classified as inflammation affecting the supporting tissue of teeth, which eventually leads to tooth loss. Mild reversible gingivitis and severe irreversible periodontitis are the most common periodontal diseases. Periodontal pathogens initiate the diseases. The bacterial toxin, lipopolysaccharide (LPS), triggers the inflammatory response and leads to oxidative stress. However, the progress of oxidative stress in periodontal diseases is unknown. The purpose of this study is to examine oxidative stress and cell damage in gingivitis and periodontitis. Our results showed that LPS increases reactive oxygen species (ROS) accumulation in gingival fibroblast (GF). However, oxidative stress resulting from excessive ROS did not influence DNA damage and cell apoptosis within 24 h. The mechanism may be related to the increased expression of DNA repair genes, Ogg1, Neil1 and Rad50. Detection of apoptosis-related proteins also showed anti-apoptotic effects and pro-apoptotic effects were balanced. The earliest damage appeared in DNA when increased gammaH2AX, an early biomarker for DNA damage, was detected in the LPS group after 48 h. Later, when recurrent inflammation persisted, 8-OHdG, a biomarker for oxidative stress was much higher in periodontitis model compared to the control in vivo. Staining of 8-OHdG in human periodontitis specimens confirmed the results. Furthermore, TUNEL staining of apoptotic cells indicated that the periodontitis model induced more cell apoptosis in gingival tissue. This suggested GF could resist early and acute inflammation (gingivitis), which was regarded as reversible, but recurrent and chronic inflammation (periodontitis) led to permanent cell damage and death. PMID- 27551476 TI - Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin 3 inhibitors. AB - Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma. PMID- 27551477 TI - Defining the minimal peptide sequence of the ING1b tumour suppressor capable of efficiently inducing apoptosis. AB - The ING1b protein is a type-II tumour suppressor and stoichiometric member of the Sin3 histone deacetylase (HDAC) protein complex in which it acts to target HDAC activity to regulate chromatin structure. Altering ING1 levels by ectopic expression of ING1b in cancer cells promotes apoptosis, whereas altering levels by knockout in normal murine fibroblasts alters sensitivity to doxorubicin induced apoptosis. We have identified a minimal region of ING1b capable of inducing levels of apoptosis in targeted cells as effectively as full-length ING1b, using transient overexpression of ING1b fragments followed by the Annexin V assay. We observed high levels of apoptosis in 14 of 14 cancer cell lines tested. Infecting triple-negative tumorigenic MDA-MB-468 breast cancer, U2OS or Saos-2 cells at multiplicities of infection (MOIs) ranging from 10 to 20 rapidly triggered apoptosis in ~80% of infected cells within 48 h. This was not due to the effects of virus, as infection at the same MOI with a control adenovirus expressing GFP was not effective in inducing apoptosis. When used at low MOIs, the ING1b fragment showed a cell-killing efficacy that was higher than native, full-length ING1b. Using a doxycycline-regulated inducible p53 expression system demonstrated that apoptosis induced by the ING1b fragment was p53 independent. Given the growing importance of combination therapies, we evaluated whether there was synergism between the ING1b fragment and HDAC inhibitors. Combination treatments with TSA, LBH 589 and SAHA reduced cancer cell survival by 3.9-4.7 fold as compared with single-drug treatment, and resulted in ~90% reduction in cell survival. Normalized isobologram analysis confirmed strong synergism between the ING1b fragment and drugs tested. These findings provide support for using ING1b-derived therapeutics as adjuvant treatments in combination with existing epigenetic therapies. PMID- 27551478 TI - FGFR1 inhibition in lung squamous cell carcinoma: questions and controversies. AB - Although the incidence of lung cancer has decreased due to the reduction of tobacco use, lung cancer remains the leading cause of cancer-related death. Lung squamous cell carcinoma represents 30% of lung cancers and only recently have possible drug-targetable mutations been identified in this disease, including fibroblast growth factor receptor 1 (FGFR1) gene amplification and genetic alterations in the phosphoinositide-3 kinase pathway. These discoveries have generated a great interest in the clinic and the initiation of clinical trials using FGFR tyrosine kinase inhibitors to treat FGFR-altered lung cancers. However, preliminary results from these studies have shown that not all patients respond to therapy. Here we review current unresolved questions on the selection of patients for their recruitment in FGFR tyrosine kinase inhibitor trials, how FGFR inhibitors could be combined with other targeted therapies or immunotherapies to improve patient outcome, and how the current preclinical models can help address these questions. PMID- 27551479 TI - Cigarette smoke-induced cell death of a spermatocyte cell line can be prevented by inactivating the Aryl hydrocarbon receptor. AB - Cigarette smoke exposure causes germ cell death during spermatogenesis. Our earlier studies demonstrated that cigarette smoke condensate (CSC) causes spermatocyte cell death in vivo and growth arrest of the mouse spermatocyte cell line (GC-2spd(ts)) in vitro via the aryl hydrocarbon receptor (AHR). We hypothesize here that inactivation of AHR could prevent the CSC-induced cell death in spermatocytes. We demonstrate that CSC exposure generates oxidative stress, which differentially regulates mitochondrial apoptosis in GC-2spd(ts) and wild type (WT) and AHR knockout (AHR-KO) mouse embryonic fibroblasts (MEFs). SiRNA-mediated silencing of Ahr augments the extent of CSC-mediated cellular damage while complementing the AHR-knockout condition. Pharmacological inhibition using the AHR-antagonist (CH223191) modulates the CSC-altered expression of apoptotic proteins and significantly abrogates DNA fragmentation though the cleavage of PARP appears AHR independent. Pretreatment with CH223191 at concentrations above 50 MUM significantly prevents the CSC-induced activation of caspase-3/7 and externalization of phosphatidylserine in the plasma membrane. However, MAPK inhibitors alone or together with CH223191 could not prevent the membrane damage upon CSC addition and the caspase-3/7 activation and membrane damage in AHR-deficient MEF indicates the interplay of multiple cell signaling and cytoprotective ability of AHR. Thus the data obtained on one hand signifies the protective role of AHR in maintaining normal cellular homeostasis and the other, could be a potential prophylactic therapeutic target to promote cell survival and growth under cigarette smoke exposed environment by receptor antagonism via CH223191-like mechanism. Antagonist-mediated inactivation of the aryl hydrocarbon receptor blocks downstream events leading to cigarette smoke induced cell death of a spermatocyte cell line. PMID- 27551481 TI - Calcium oxalate toxicity in renal epithelial cells: the mediation of crystal size on cell death mode. AB - The cytotoxicity of calcium oxalate (CaOx) in renal epithelial cells has been studied extensively, but the cell death mode induced by CaOx with different physical properties, such as crystal size and crystal phase, has not been studied in detail. In this study, we comparatively investigated the differences of cell death mode induced by nano-sized (50 nm) and micron-sized (10 MUm) calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) to explore the cell death mechanism. The effect of the exposure of nano-/micron-sized COM and COD crystals toward the African green monkey renal epithelial (Vero) cells were investigated by detecting cell cytoskeleton changes, lysosomal integrity, mitochondrial membrane potential (Deltapsim), apoptosis and/or necrosis, osteopontin (OPN) expression, and malondialdehyde (MDA) release. Nano-/micron sized COM and COD crystals could cause apoptosis and necrosis simultaneously. Nano-sized crystals primarily caused apoptotic cell death, leading to cell shrinkage, phosphatidylserine ectropion, and nuclear shrinkage, whereas micron sized crystals primarily caused necrotic cell death, leading to cell swelling and cell membrane and lysosome rupture. Nano-sized COM and COD crystals induced much greater cell death (sum of apoptosis and necrosis) than micron-sized crystals, and COM crystals showed higher cytotoxicity than the same-sized COD crystals. Both apoptosis and necrosis could lead to mitochondria depolarization and elevate the expression of OPN and the generation of lipid peroxidation product MDA. The amount of expressed OPN and generated MDA was positively related to cell injury degree. The physicochemical properties of crystals could affect the cell death mode. The results of this study may provide a basis for future studies on cell death mechanisms. PMID- 27551480 TI - Factor VII promotes hepatocellular carcinoma progression through ERK-TSC signaling. AB - We previously demonstrated PAR2 starts upstreamed with tissue factor (TF) and factor VII (FVII), inhibited autophagy via mTOR signaling in HCC. However, the mechanism underlying for merging functions of PAR2 with the coagulation system in HCC progression remained unclear. The present study aimed to investigate the role of TF, FVII and PAR2 in tumor progression of HCC. The expressions of TF, FVII and PAR2 from HCC specimens were evaluated by immunohistochemical stains and western blotting. We found that the expression of FVII, but not TF and PAR2, directly related to the vascular invasion and the clinical staging. Importantly, a lower level of FVII expression was significantly associated with the longer disease free survival. The addition of FVII but not TF induced the expression of PAR2 and phosphorylation of ERK1/2, whereas knockdown of FVII decreased PAR2 expression and ERK1/2 phosphorylation in HCC cell lines. Furthermore, levels of phosphor TSC2 (Ser664) were increased after treatment with FVII and PAR2 agonist whereas these were significantly abolished in the presence of a potent and specific MEK/ERK inhibitor U0126. Moreover, mTOR knockdown highly reduced Hep3B migration, which could be reverted by FVII but not TF and PAR2. These results indicated that FVII/PAR2 signaling through MEK/ERK and TSC2 axis for mTOR activation has potent effects on the migration of HCC cells. In addition, FVII/PAR2 signaling elicits an mTOR-independent signaling, which promotes hepatoma cell migration in consistent with the clinical observations. Our study indicates that levels of FVII, but not TF, are associated with tumor migration and invasiveness in HCC, and provides clues that evaluation of FVII expression in HCC may be useful as a prognostic indicator in patients with HCC and may form an alternative target for further therapy. PMID- 27551482 TI - Secondary necrotic neutrophils release interleukin-16C and macrophage migration inhibitory factor from stores in the cytosol. AB - Neutrophils harbor a number of preformed effector proteins that allow for immediate antimicrobial functions without the need for time-consuming de novo synthesis. Evidence indicates that neutrophils also contain preformed cytokines, including interleukin (IL)-1ra, CXCL8 and CXCL2. In the search for additional preformed cytokines, a cytokine array analysis identified IL-16 and macrophage migration inhibitory factor (MIF) as preformed cytokines in lysates from human primary neutrophils. Both IL-16 and MIF are unconventional cytokines because they lack a signal sequence. Using confocal immunofluorescence microscopy as well as western blot analysis of subcellular fractions, IL-16 and MIF were found to be stored in the cytosol rather than in the granules of human neutrophils, which implies an unconventional secretion mechanism for both cytokines. IL-16 is synthesized and stored as a precursor (pre-IL-16). We present evidence that the processing of pre-IL-16 to the biologically active IL-16C is mediated by caspase 3 and occurs during both spontaneous and UV-induced apoptosis of human neutrophils. Although IL-16 processing occurs during apoptosis, IL-16C and MIF release was observed only during secondary necrosis of neutrophils. Screening a panel of microbial substances and proinflammatory cytokines did not identify a stimulus that induced the release of IL-16C and MIF independent of secondary necrosis. The data presented here suggest that IL-16 and MIF are neutrophil derived inflammatory mediators released under conditions of insufficient clearance of apoptotic neutrophils, as typically occurs at sites of infection and autoimmunity. PMID- 27551483 TI - c-MYC responds to glucose deprivation in a cell-type-dependent manner. AB - Metabolic reprogramming supports cancer cells' demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer. PMID- 27551484 TI - Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa. AB - Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP. PMID- 27551485 TI - Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models. AB - The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID- 27551486 TI - Resveratrol chemosensitizes HER-2-overexpressing breast cancer cells to docetaxel chemoresistance by inhibiting docetaxel-mediated activation of HER-2-Akt axis. AB - As breast cancer cells often develop chemoresistance, better therapeutic options are in search to circumvent it. Here we demonstrate that human epidermal growth factor receptor-2 (HER-2)-overexpressing breast cancer cells resist docetaxel induced cytotoxicity by upregulating HER-2 and its activity downstream, through Akt and mitogen-activated protein kinase (MAPK) pathways. We observed that introducing resveratrol as a chemosensitizer in docetaxel chemotherapy blocks upregulation and activation of HER-2 in addition to blocking downstream signaling pathways such as Akt. Resveratrol and docetaxel combination results in the synergistic induction of cell death in HER-2-overexpressing SK-BR-3 cells, whereas introduction of wild-type HER-2 in MDA-MD-231 cells increased the resistance to docetaxel. Dominant-negative HER-2 sensitizes SK-BR-3 cells to docetaxel. Our study identified a new synergistic therapeutic combination that targets HER-2-induced breast cancer resistance and might help to overcome therapeutic resistance during breast cancer therapy. The synergism of docetaxel and resveratrol was maximum in SK-BR-3, which is unique among the cell lines studied, due to its high expression status of HER-2, a receptor known to dictate the signaling environment of breast cancer cells. Docetaxel could further induce HER-2 activity in these cells, which was downregulated on resveratrol treatment. Transfection of DN-HER-2 in SK-BR-3 cells inhibits the synergism as the transfection itself sensitizes these cells to docetaxel, leaving no role for resveratrol, whereas ectopic expression of HER-2 introduces the synergism in MDA MB-231, the triple-negative cell line, in which the synergism was minimum, attesting the crucial role of HER-2 in suppressing the sensitivity to docetaxel. Single-agent docetaxel induced HER-2-mediated resistance to cell death, which was blocked by resveratrol. Resveratrol also downregulated docetaxel-induced activation of MAPK and Akt, survival signaling pathways downstream of HER-2. In short, this study, for the first time, establishes the role of HER-2-Akt signaling axis in regulating the synergistic effect of docetaxel and resveratrol in breast cancer cells overexpressing HER-2. PMID- 27551487 TI - AMPK maintains energy homeostasis and survival in cancer cells via regulating p38/PGC-1alpha-mediated mitochondrial biogenesis. AB - Cancer cells exhibit unique metabolic response and adaptation to the fluctuating microenvironment, yet molecular and biochemical events imprinting this phenomenon are unclear. Here, we show that metabolic homeostasis and adaptation to metabolic stress in cancer cells are primarily achieved by an integrated response exerted by the activation of AMPK. We provide evidence that AMPK-p38-PGC-1alpha axis, by regulating energy homeostasis, maintains survival in cancer cells under glucose limiting conditions. Functioning as a molecular switch, AMPK promotes glycolysis by activating PFK2, and facilitates mitochondrial metabolism of non-glucose carbon sources thereby maintaining cellular ATP level. Interestingly, we noted that AMPK can promote oxidative metabolism via increasing mitochondrial biogenesis and OXPHOS capacity via regulating expression of PGC-1alpha through p38MAPK activation. Taken together, our study signifies the fundamental role of AMPK in controlling cellular bioenergetics and mitochondrial biogenesis in cancer cells. PMID- 27551488 TI - Blood vessels and cancer much more than just angiogenesis. PMID- 27551490 TI - Sundew plant, a potential source of anti-inflammatory agents, selectively induces G2/M arrest and apoptosis in MCF-7 cells through upregulation of p53 and Bax/Bcl 2 ratio. AB - The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough. The present study is designed to substantiate the potential of D. burmannii in in vitro anticancer activity and its relation with anti-inflammatory property. In vitro anticancer study revealed that DBME is inhibiting the proliferation of MCF-7 cells without affecting the viability of other malignant and non-malignant cells. DBME induced G2/M phase arrest and apoptosis in MCF-7 cells by suppressing the expression of cyclin A1, cyclin B1 and Cdk-1 and increasing the expression of p53, Bax/Bcl-2 ratio leading to activation of caspases and PARP degradation. Presence of caspase-8 (Z-IETD fmk) and caspase-9 (Z-LEHD-fmk) inhibitors alone did prevent the apoptosis partially while apoptosis prevention was significantly observed when used in combination, suggesting vital role of caspases in DBME-induced apoptosis in MCF-7 cells. DBME also downregulated LPS-induced increased expression of iNOS, COX-2 and TNF-alpha along with suppression on intracellular ROS production that confirms the potential of DBME as anti-inflammatory extract. GCMS analysis revealed the presence of four major compounds hexadecanoic acid, tetradecanoic acid, hexadecen-1-ol, trans-9 and 1-tetradecanol along with some other fatty acid derivatives and carotenoids (Beta-doradecin) in DBME. These findings confirmed the anti-inflammatory activity of DBME, which is already listed in French Pharmacopeia in 1965. Here we have additionally reported the anti-breast cancer activity of DBME and its relation to the anti-inflammatory potential. Hence, an ethnopharmacological approach can be considered as useful tool for the discovery of new drug leads. PMID- 27551491 TI - Autophagy mediated by arginine depletion activation of the nutrient sensor GCN2 contributes to interferon-gamma-induced malignant transformation of primary bovine mammary epithelial cells. AB - Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-gamma has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-gamma can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-gamma treatment, autophagy and malignant transformation and of the mechanism underlying IFN-gamma-induced autophagy and subsequent malignant transformation in primary BMECs. IFN-gamma levels were significantly increased in cattle that received normal long-term dietary corn straw (CS) roughage supplementation. In addition, an increase in autophagy was clearly observed in the BMECs from the mammary tissue of cows expressing high levels of IFN-gamma. In vitro, autophagy was clearly induced in primary BMECs by IFN-gamma within 24 h. This induced autophagy could subsequently promote dramatic primary BMEC transformation. Furthermore, we found that IFN-gamma promoted arginine depletion, activated the general control nonderepressible-2 kinase (GCN2) signalling pathway and resulted in an increase in autophagic flux and the amount of autophagy in BMECs. Overall, our findings are the first to demonstrate that arginine depletion and kinase GCN2 expression mediate IFN-gamma-induced autophagy that may promote malignant progression and that immunometabolism, autophagy and cancer are strongly correlated. These results suggest new directions and paths for preventing and treating breast cancer in relation to diet. PMID- 27551493 TI - Expression of the anti-apoptotic BAG3 protein in leg venous ulcerative tissues. PMID- 27551492 TI - A Bowman-Birk inhibitor induces apoptosis in human breast adenocarcinoma through mitochondrial impairment and oxidative damage following proteasome 20S inhibition. AB - Proteasome inhibitors are emerging as a new class of chemopreventive agents and have gained huge importance as potential pharmacological tools in breast cancer treatment. Improved understanding of the role played by proteases and their specific inhibitors in humans offers novel and challenging opportunities for preventive and therapeutic intervention. In this study, we demonstrated that the Bowman-Birk protease inhibitor from Vigna unguiculata seeds, named black-eyed pea trypsin/chymotrypsin Inhibitor (BTCI), potently suppresses human breast adenocarcinoma cell viability by inhibiting the activity of proteasome 20S. BTCI induced a negative growth effect against a panel of breast cancer cells, with a concomitant cytostatic effect at the G2/M phase of the cell cycle and an increase in apoptosis, as observed by an augmented number of cells at the sub-G1 phase and annexin V-fluorescin isothiocyanate (FITC)/propidium iodide (PI) staining. In contrast, BTCI exhibited no cytotoxic effect on normal mammary epithelial cells. Moreover, the increased levels of intracellular reactive oxygen species (ROS) and changes in the mitochondrial membrane potential in cells treated with BTCI indicated mitochondrial damage as a crucial cellular event responsible for the apoptotic process. The higher activity of caspase in tumoral cells treated with BTCI in comparison with untreated cells suggests that BTCI induces apoptosis in a caspase-dependent manner. BTCI affected NF-kB target gene expression in both non invasive and invasive breast cancer cell lines, with the effect highly pronounced in the invasive cells. An increased expression of interleukin-8 (IL-8) in both cell lines was also observed. Taken together, these results suggest that BTCI promotes apoptosis through ROS-induced mitochondrial damage following proteasome inhibition. These findings highlight the pharmacological potential and benefit of BTCI in breast cancer treatment. PMID- 27551494 TI - Functional characterization of the ectopically expressed olfactory receptor 2AT4 in human myelogenous leukemia. AB - The olfactory receptor (OR) family was found to be expressed mainly in the nasal epithelium. In the last two decades members of the OR family were detected to be functional expressed in different parts of the human body such as in liver, prostate or intestine cancer cells. Here, we detected the expression of several ORs in the human chronic myelogenous leukemia (CML) cell line K562 and in white blood cells of clinically diagnosed acute myeloid leukemia (AML) patients by RT PCR and next-generation sequencing. With calcium-imaging, we characterized in greater detail the cell biological role of one OR (OR2AT4) in leukemia. In both cell systems, the OR2AT4 agonist Sandalore-evoked strong Ca(2+) influx via the adenylate cyclase-cAMP-mediated pathway. The OR2AT4 antagonist Phenirat prevented the Sandalore-induced intracellular Ca(2+) increase. Western blot and flow cytometric experiments revealed that stimulation of OR2AT4 reduced the proliferation by decreasing p38-MAPK phosphorylation and induced apoptosis via phosphorylation of p44/42-MAPK. Furthermore, Sandalore increased the number of hemoglobin-containing cells in culture. We described for the first time an OR mediated pathway in CML and AML that can regulate proliferation, apoptosis and differentiation after activation. This mechanism offers novel therapeutic options for the treatment of AML. PMID- 27551495 TI - Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells. AB - Autophagic activity reflects cellular response to drug treatment and can be regulated by STAT3 signaling. Resveratrol inhibits STAT3 activation and causes remarkable growth arrest and cell death of ovarian cancer (OC) cells. However, the autophagic status and its relevance with resveratrol's anti-OC effects remain unclear. We analyzed the states of autophagic activities, the nature of autophagosomes and the levels of autophagy-related proteins (LC-3, Beclin 1 and STAT3) in resveratrol-treated CAOV-3 and OVCAR-3 OC cells using multiple approaches. We elucidated the correlation of STAT3 inhibition with autophagic activity by treating OC cells with an upstream inhibitor of STAT proteins, AG490. Resveratrol efficiently suppressed growth, induced apoptosis and inactivated STAT3 signaling of the two OC cell lines. We found enhanced autophagic activity accompanied with Beclin-1 upregulation and LC3 enzymatic cleavage in resveratrol treated OC cells. Immunofluorescent (IF) microscopic and IF-based confocal examinations demonstrated the accumulation of cytoplasmic granules co-labeled with LC3 and cytochrome C in resveratrol- or AG490-treated OC cells. Using electron microscopy, we confirmed an increase in autophagosomes and mitochondrial spheroids in either resveratrol- or AG490-treated OC cells. This study demonstrates the abilities of resveratrol to enhance apoptotic and autophagic activities in OC cells, presumably via inactivating STAT3 signaling. Resveratrol or the selective JAK2 inhibitor also leads to mitochondrial turnover, which would be unfavorable for OC cell survival and sensitize OC cells to resveratrol. PMID- 27551496 TI - Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. AB - Imeglimin is the first in a new class of oral glucose-lowering agents, having recently completed its phase 2b trial. As Imeglimin did show a full prevention of beta-cell apoptosis, and since angiopathy represents a major complication of diabetes, we studied Imeglimin protective effects on hyperglycemia-induced death of human endothelial cells (HMEC-1). These cells were incubated in several oxidative stress environments (exposure to high glucose and oxidizing agent tert butylhydroperoxide) which led to mitochondrial permeability transition pore (PTP) opening, cytochrome c release and cell death. These events were fully prevented by Imeglimin treatment. This protective effect on cell death occurred without any effect on oxygen consumption rate, on lactate production and on cytosolic redox or phosphate potentials. Imeglimin also dramatically decreased reactive oxygen species production, inhibiting specifically reverse electron transfer through complex I. We conclude that Imeglimin prevents hyperglycemia-induced cell death in HMEC-1 through inhibition of PTP opening without inhibiting mitochondrial respiration nor affecting cellular energy status. Considering the high prevalence of macrovascular and microvascular complications in type 2 diabetic subjects, these results together suggest a potential benefit of Imeglimin in diabetic angiopathy. PMID- 27551497 TI - PKC activation sensitizes basal-like breast cancer cell lines to Smac mimetics. AB - There is a need for novel strategies to initiate cancer cell death. One approach is the use of Smac mimetics, which antagonize inhibitor of apoptosis proteins (IAPs). Recent studies have shown that combinations of Smac mimetics such as LBW242 or LCL161 in combination with chemotherapeutic agents increase cancer cell death. Here we show that the protein kinase C (PKC) activator TPA together with the Smac mimetic LBW242 induces cell death in two basal breast cancer cell lines (MDA-MB-468 and BT-549) that are resistant to Smac mimetic as single agent. Ten other LBW242-insensitive cancer cell lines were not influenced by the TPA+LBW242 combination. The TPA+LBW242 effect was suppressed by the PKC inhibitor GF109203X, indicating dependence on PKC enzymatic activity. The PKC effect was mediated via increased synthesis and release of TNFalpha, which can induce death in the presence of Smac mimetics. The cell death, coinciding with caspase-3 cleavage, was suppressed by caspase inhibition and preceded by the association of RIP1 with caspase-8, as seen in complex II formation. Smac mimetics, but not TPA, induced the non-canonical NF-kappaB pathway in both MDA-MB-231 and MDA-MB-468 cells. Blocking the canonical NF-kappaB pathway suppressed TPA induction of TNFalpha in MDA-MB-468 cells whereas isolated downregulation of either the canonical or non canonical pathways did not abolish the Smac mimetic induction of the NF-kappaB driven genes TNFalpha and BIRC3 in MDA-MB-231 cells although the absolute levels were suppressed. A combined downregulation of the canonical and non-canonical pathways further suppressed TNFalpha levels and inhibited Smac mimetic-mediated cell death. Our data suggest that in certain basal breast cancer cell lines co treatment of TPA with a Smac mimetic induces cell death highlighting the potential of using these pathways as molecular targets for basal-like breast cancers. PMID- 27551498 TI - Mitochondrial oligomers boost glycolysis in cancer stem cells to facilitate blebbishield-mediated transformation after apoptosis. AB - Apoptosis culminates in secondary necrosis due to lack of ATP. Cancer stem cells form spheres after apoptosis by evoking the blebbishield emergency program. Hence, determining how blebbishields avoid secondary necrosis is crucial. Here we demonstrate that N-Myc and VEGFR2 control transformation from blebbishields, during which oligomers of K-Ras, p27, BAD, Bax, and Bak boost glycolysis to avoid secondary necrosis. Non-apoptotic cancer cells also utilize oligomers to boost glycolysis, which differentiates the glycolytic function of oligomers from their apoptotic action. Smac mimetic in combination with TNF-alpha or TRAIL but not in combination with FasL abrogates transformation from blebbishields by inducing secondary necrosis. Thus blebbishield-mediated transformation is dependent on glycolysis, and Smac mimetics represent potential candidates to abrogate the blebbishield emergency program. PMID- 27551499 TI - NGF sensitizes TrkA SH-SY5Y neuroblastoma cells to TRAIL-induced apoptosis. AB - We report a novel pro-apoptotic function for nerve growth factor (NGF) and its tropomyosin-related kinase A (TrkA) receptor in sensitizing TRAIL (TNF-related apoptotis-inducing ligand)-resistant SH-SY5Y neuroblastoma (NB) cells to TRAIL induced apoptosis, resulting in the abrogation of anchorage-independent tumourigenic growth in vitro. We show that the TRAIL-resistant SH-SY5Y phenotype is cFLIP (cellular FLICE-like inhibitory protein) dependent and not due to low level functional TRAIL receptor or caspase expression or an inhibitory equilibrium between functional and decoy TRAIL receptors or B-cell lymphoma 2 (Bcl-2) and BH3-only (Bcl-2 homology domain 3-only) family proteins. NGF sensitization of SH-SY5Y cells to TRAIL-induced apoptosis was dependent upon TrkA expression, activation and subsequent sequestration of cFLIP. This reduces cFLIP recruitment to TRAIL-activated death receptors and increases the recruitment of caspase-8, leading to TRAIL-induced, caspase-dependent, type II apoptosis via the intrinsic mitochondrial pathway. This effect was temporary, inhibited within 6 h by nuclear factor-kappa binding (NF-kappaB)-mediated increase in myeloid cell leukaemia-1 (Mcl-1) expression, abrogated by transient cFLIP or B-cell lymphoma extra large (Bcl-xL) overexpression and optimized by NF-kappaB and Mcl-1 inhibitors. This novel mechanism adds an important pro-apoptotic immunological dimension to NGF/TrkA interaction that may not only help to explain the association between TrkA expression, better prognosis and spontaneous remission in NB, but also provides a novel potential pro-apoptotic therapeutic use for NGF, TRAIL and inhibitors of NF-kappaB and/or Mcl-1 in favourable and unfavourable NBs that express TrkA and exhibit cFLIP-mediated TRAIL resistance. PMID- 27551500 TI - alphaTAT1 downregulation induces mitotic catastrophe in HeLa and A549 cells. AB - alpha-Tubulin acetyltransferase 1 (alphaTAT1) controls reversible acetylation on Lys40 of alpha-tubulin and modulates multiple cellular functions. alphaTAT1 depletion induced morphological defects of touch receptor neurons in Caenorhabditis elegans and impaired cell adhesion and contact inhibition in mouse embryonic fibroblasts, however, no morphological or proliferation defects in human RPE-hTERT cells were found after alphaTAT1-specific siRNA treatment. Here, we compared the effect of three alphaTAT1-specific shRNAs on proliferation and morphology in two human cell lines, HeLa and A549. The more efficient two shRNAs induced mitotic catastrophe in both cell lines and the most efficient one also decreased F-actin and focal adhesions. Further analysis revealed that alphaTAT1 downregulation increased gamma-H2AX, but not other DNA damage markers p-CHK1 and p-CHK2, along with marginal change in microtubule outgrowth speed and inter kinetochore distance. Overexpression of alphaTAT1 could not precisely mimic the distribution and concentration of endogenous acetylated alpha-tubulin (Ac-Tu), although no overt phenotype change was observed, meanwhile, this could not completely prevent alphaTAT1 downregulation-induced deficiencies. We therefore conclude that efficient alphaTAT1 downregulation could impair actin architecture and induce mitotic catastrophe in HeLa and A549 cells through mechanisms partly independent of Ac-Tu. PMID- 27551501 TI - Systematic selection of small molecules to promote differentiation of embryonic stem cells and experimental validation for generating cardiomyocytes. AB - Small molecules are being increasingly used for inducing the targeted differentiation of stem cells to different cell types. However, until now no systematic method for selecting suitable small molecules for this purpose has been presented. In this work, we propose an integrated and general bioinformatics and cheminformatics-based approach for selecting small molecules which direct cellular differentiation in the desired way. The approach was successfully experimentally validated for differentiating stem cells into cardiomyocytes. All predicted compounds enhanced expression of cardiac progenitor (Gata4, Nkx2-5 and Mef2c) and mature cardiac markers (Actc1, myh6) significantly during and post cardiac progenitor formation. The best-performing compound, Famotidine, increased the percentage of Myh6-positive cells from 33 to 56%, and enhanced the expression of Nkx2.5 and Tnnt2 cardiac progenitor and cardiac markers in protein level. The approach employed in the study is applicable to all other stem cell differentiation settings where gene expression data are available. PMID- 27551502 TI - Development of a lytic peptide derived from BH3-only proteins. AB - Despite great advances in cancer therapy, drug resistance is a difficult hurdle to overcome that requires development of anticancer agents with novel and effective modes of action. In a number of studies, lytic peptides have shown remarkable ability to eliminate cancer cells through a different way from traditional treatments. Lytic peptides are positively charged, amphiphilic, and are efficient at binding and disrupting the negatively charged cell membrane of cancer cells. In this study, we described the anticancer properties of a lytic peptide that was developed on the basis of the alignment of amphiphilic BH3 peptides. Our results demonstrated that the positive charge and conformation constraint were favourable for efficient cancer cell elimination. Artificial BCL 2 homology 3 peptides (ABH3) exhibited effective anticancer effects against a series of cancer cell lines in vitro and in HeLa human cervical tumour xenografts in vivo. ABH3 induced cell death in an apoptosis-independent manner through the lytic properties of the peptide that caused disruption of cell membrane. Our results showed that charge tuning and conformation constraining in a lytic peptide could be applied to optimise the anticancer activity of lytic peptides. These results also suggest that ABH3 may be a promising beginning for the development of additional lytic peptides as anticancer reagents. PMID- 27551503 TI - Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice. AB - Gender-specific differences are commonly found in metabolic pathways and in response to nutritional manipulation. Previously, we identified a role for caspase-2 in age-related glucose homeostasis and lipid metabolism using male caspase-2-deficient (Casp2 (-/-) ) mice. Here we show that the resistance to age induced glucose tolerance does not occur in female Casp2 (-/-) mice and it appears to be independent of insulin sensitivity in males. Using fasting (18 h) as a means to further investigate the role of caspase-2 in energy and lipid metabolism, we identified sex-specific differences in the fasting response and lipid mobilization. In aged (18-22 months) male Casp2 (-/-) mice, a significant decrease in fasting liver mass, but not total body weight, was observed while in females, total body weight, but not liver mass, was reduced when compared with wild-type (WT) animals. Fasting-induced lipolysis of adipose tissue was enhanced in male Casp2 (-/-) mice as indicated by a significant reduction in white adipocyte cell size, and increased serum-free fatty acids. In females, white adipocyte cell size was significantly smaller in both fed and fasted Casp2 (-/-) mice. No difference in fasting-induced hepatosteatosis was observed in the absence of caspase-2. Further analysis of white adipose tissue (WAT) indicated that female Casp2 (-/-) mice may have enhanced fatty acid recycling and metabolism with expression of genes involved in glyceroneogenesis and fatty acid oxidation increased. Loss of Casp2 also increased fasting-induced autophagy in both male and female liver and in female skeletal muscle. Our observations suggest that caspase-2 can regulate glucose homeostasis and lipid metabolism in a tissue and sex-specific manner. PMID- 27551504 TI - Deorphanization and characterization of the ectopically expressed olfactory receptor OR51B5 in myelogenous leukemia cells. AB - The ectopic expression of olfactory receptors (ORs) in the human body has been of major interest in the past decade. Several studies have reported the expression of ORs not only in healthy tissues such as heart, sperm or skin cells, but also in cancerous tissues of the liver, prostate or intestine. In the present study, we detected the expression of OR51B5 in the chronic myelogenous leukemia (CML) cell line K562 and in white blood cell samples of clinically diagnosed acute myelogenous leukemia (AML) patients by reverse transcription-PCR and immunocytochemical staining. The known OR51B5 ligand isononyl alcohol increased the levels of intracellular Ca(2+) in both AML patient blood cells and K562 cells. With calcium imaging experiments, we characterized in greater detail the OR51B5-mediated signaling pathway. Here, we observed an involvement of adenylate cyclase and the downstream L-type and T-type calcium channels. In addition, the activation of OR51B5 leads to an inhibition of cell proliferation in K562 cells. In western blot experiments, we found that incubation with isononyl alcohol led to a reduction in p38-MAPK (mitogen-activated protein kinase) phosphorylation that might be responsible for the decreased cell proliferation. In the present study, we characterized the OR51B5-mediated signaling pathway downstream of the activation with isononyl alcohol, which leads to reduced proliferation and therefore provide a novel pharmacological target for CML and AML, the latter of which remains difficult to treat. PMID- 27551505 TI - Induction and inhibition of the pan-nuclear gamma-H2AX response in resting human peripheral blood lymphocytes after X-ray irradiation. AB - Human peripheral blood lymphocytes (HPBLs) are one of the most sensitive cells to ionizing radiation (IR) in the human body, and IR-induced DNA damage and functional impairment of HPBLs are the adverse consequences of IR accidents and major side effects of radiotherapy. Phosphorylated H2AX (gammaH2AX) is a sensitive marker for DNA double-strand breaks, but the role and regulation of the pan-nuclear gammaH2AX response in HPBLs after IR remain unclear. We herein demonstrated that the pan-nuclear gammaH2AX signals were increased in a time- and dose-dependent manner, colocalized with >94% of TUNEL apoptotic staining, and displayed a typical apoptotic pattern in resting HPBLs after low LET X-ray IR. In addition, the X-irradiation-induced pan-nuclear p-ATM and p-DNA-PKcs responses also occurred in resting HPBLs, and were colocalized with 92-95% of TUNEL staining and 97-98% of the pan-nuclear gammaH2AX signals, respectively, with a maximum at 6 h post irradiation, but disappeared at 24 h post irradiation. Moreover, ATM/DNA-PKcs inhibitor KU55933, p53 inhibitor PFT-MU and pan-caspase inhibitor ZVAD-fmk significantly decreased X-irradiation-induced pan-nuclear gammaH2AX signals and TUNEL staining, protected HPBLs from apoptosis, but decreased the proliferative response to mitogen in X-irradiated HPBLs. Notably, whereas both KU55933 and PFT-MU increased the IR-induced chromosome breaks and mis-repair events through inhibiting the formation of p-ATM, p-DNA-PKcs and gammaH2AX foci in X-irradiated HPBLs, the ZVAD-fmk did not increase the IR induced chromosomal instability. Taken together, our data indicate that pan nuclear gammaH2AX response represents an apoptotic signal that is triggered by the transient pan-nuclear ATM and DNA-PKcs activation, and mediated by p53 and pan-caspases in X-irradiated HPBLs, and that caspase inhibitors are better than ATM/DNA-PKcs inhibitors and p53 inhibitors to block pan-nuclear gammaH2AX response/apoptosis and protect HPBLs from IR. PMID- 27551506 TI - Cathepsin B launches an apoptotic exit effort upon cell death-associated disruption of lysosomes. AB - The release of cathepsin proteases from disrupted lysosomes results in lethal cellular autodigestion. Lysosomal disruption-related cell death is highly variable, showing both apoptotic and necrotic outcomes. As the substrate spectrum of lysosomal proteases encompasses the apoptosis-regulating proteins of the Bcl-2 family, their degradation could influence the cell death outcome upon lysosomal disruption. We used Forster resonance energy transfer (FRET)-based biosensors to image the real-time degradation of the Bcl-2-family members, Bcl-xl, Bax and Bid, in living cells undergoing lysosomal lysis and identified an early chain of proteolytic events, initiated by the release of cathepsin B, which directs cells toward apoptosis. In this apoptotic exit strategy, cathepsin B's proteolytic activity results in apoptosis-inducing Bid and removes apoptosis-preventing Bcl xl. Cathepsin B furthermore appears to degrade a cystein protease that would otherwise have eliminated apoptosis-supporting Bax, indirectly keeping cellular levels of the Bax protein up. The concerted effort of these three early events shifts the balance of cell fate away from necrosis and toward apoptosis. PMID- 27551508 TI - Hepatitis B virus and inhibitor of apoptosis proteins - a vulnerable liaison. PMID- 27551507 TI - Upregulation of GADD45alpha in light-damaged retinal pigment epithelial cells. AB - To better understand the molecular mechanisms responsible for light-induced damage in retinal pigmented epithelial (RPE) cells, we developed an automated device to recapitulate intense light exposure. When compared with human fibroblasts, ARPE-19 cells that had been exposed to blue-rich light-emitting diode-light of 10 000 Lux at 37 degrees C for 9 h displayed dramatic cellular apoptosis. Collectively, gene expression profiling and qPCR demonstrated that growth arrest and DNA damage-45alpha (GADD45alpha) expression was markedly upregulated. Transient knockdown of GADD45alpha partially attenuated light-damage induced apoptosis in ARPE-19 cells, whereas GADD45alpha overexpression dramatically increased it. These results demonstrate the critical function of GADD45alpha in light-induced RPE cellular apoptosis. Quantitative reverse transcription-PCR and western blotting revealed that the upregulation of GADD45alpha was under direct control of p53. Moreover, treatment with Ly294002, an inhibitor of AKT phosphorylation, further promoted GADD45alpha gene transcription in both non-light and light-damaged ARPE-19 cells. Treatment also exacerbated RPE cellular apoptosis after light exposure, confirming that inhibition of Akt phosphorylation increases GADD45alpha expression. Collectively, our findings reveal that light irrigation induces human RPE cellular apoptosis through upregulation of GADD45alpha expression mediated through both the p53 and phosphatidylinositol 3-kinase-AKT signaling pathways. These results provide new insights into human retinal diseases elicited by light damage and open a new avenue for disease prevention and treatment. PMID- 27551509 TI - DeltaNp63alpha modulates histone methyl transferase SETDB1 to transcriptionally repress target genes in cancers. PMID- 27551510 TI - Mitochondrial DNA plasticity is an essential inducer of tumorigenesis. AB - Although mitochondrial DNA has been implicated in diseases such as cancer, its role remains to be defined. Using three models of tumorigenesis, namely glioblastoma multiforme, multiple myeloma and osteosarcoma, we show that mitochondrial DNA plays defining roles at early and late tumour progression. Specifically, tumour cells partially or completely depleted of mitochondrial DNA either restored their mitochondrial DNA content or actively recruited mitochondrial DNA, which affected the rate of tumorigenesis. Nevertheless, non depleted tumour cells modulated mitochondrial DNA copy number at early and late progression in a mitochondrial DNA genotype-specific manner. In glioblastoma multiforme and osteosarcoma, this was coupled with loss and gain of mitochondrial DNA variants. Changes in mitochondrial DNA genotype affected tumour morphology and gene expression patterns at early and late progression. Importantly, this identified a subset of genes that are essential to early progression. Consequently, mitochondrial DNA and commonly expressed early tumour-specific genes provide novel targets against tumorigenesis. PMID- 27551511 TI - Xenon-mediated neuroprotection in response to sustained, low-level excitotoxic stress. AB - Noble gases such as xenon and argon have been reported to provide neuroprotection against acute brain ischemic/anoxic injuries. Herein, we wished to evaluate the protective potential of these two gases under conditions relevant to the pathogenesis of chronic neurodegenerative disorders. For that, we established cultures of neurons typically affected in Alzheimer's disease (AD) pathology, that is, cortical neurons and basal forebrain cholinergic neurons and exposed them to L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) to generate sustained, low-level excitotoxic stress. Over a period of 4 days, PDC caused a progressive loss of cortical neurons which was prevented substantially when xenon replaced nitrogen in the cell culture atmosphere. Unlike xenon, argon remained inactive. Xenon acted downstream of the inhibitory and stimulatory effects elicited by PDC on glutamate uptake and efflux, respectively. Neuroprotection by xenon was mimicked by two noncompetitive antagonists of NMDA glutamate receptors, memantine and ketamine. Each of them potentiated xenon-mediated neuroprotection when used at concentrations providing suboptimal rescue to cortical neurons but most surprisingly, no rescue at all. The survival-promoting effects of xenon persisted when NMDA was used instead of PDC to trigger neuronal death, indicating that NMDA receptor antagonism was probably accountable for xenon's effects. An excess of glycine failed to reverse xenon neuroprotection, thus excluding a competitive interaction of xenon with the glycine-binding site of NMDA receptors. Noticeably, antioxidants such as Trolox and N-acetylcysteine reduced PDC-induced neuronal death but xenon itself lacked free radical-scavenging activity. Cholinergic neurons were also rescued efficaciously by xenon in basal forebrain cultures. Unexpectedly, however, xenon stimulated cholinergic traits and promoted the morphological differentiation of cholinergic neurons in these cultures. Memantine reproduced some of these neurotrophic effects, albeit with less efficacy than xenon. In conclusion, we demonstrate for the first time that xenon may have a therapeutic potential in AD. PMID- 27551512 TI - Questions and controversies in innate immune research: what is the physiological role of NLRP3? AB - The NLRP3 inflammasome is a key component of the innate immune system that induces pro-inflammatory cytokine production and cell death. Although NLRP3 is activated by many pathogens, it only appears to be critical for host defense for a limited number of specific infections. NLRP3 is however strongly associated with the initiation and pathology of many inflammatory diseases. If NLRP3 function is largely redundant for host defense, but drives a number of inflammatory diseases, this raises the important question of why evolution has elected to maintain NLRP3 function. We propose that the primary physiological functions of NLRP3 in health are to engage pathways to clear noxious substances (e.g. protein aggregates and crystals), and to regulate metabolism. We discuss the newly identified functions for NLRP3 in metabolic homeostasis, and how NLRP3 beneficial functions in homeostasis may become detrimental during the onset of inflammatory and metabolic diseases. A common feature of most NLRP3-driven diseases is that they are associated with ageing or metabolic excess, and indeed, Nlrp3 deficiency promotes 'healthspan' in ageing mice. This suggests that beneficial functions of NLRP3 in youth may become increasingly countered by NLRP3 dependent pathology as an individual ages, and we propose a general model by which ageing or nutrient excess may provide a tipping point to switch NLRP3 function from beneficial to pathological. The physiological role of NLRP3 in healthy individuals remains incompletely understood and future research will need to address this if NLRP3 is to become a successful therapeutic target for the clinical management of inflammatory diseases. PMID- 27551513 TI - Macrophage-mediated chronic lymphocytic leukemia cell survival is independent of APRIL signaling. AB - Survival of chronic lymphocytic leukemia (CLL) cells is mainly driven by interactions within the lymph node (LN) microenvironment with bystander cells such as T cells or cells from the monocytic lineage. Although the survival effect by T cells is largely governed by the TNFR ligand family member CD40L, the exact mechanism of monocyte-derived cell-induced survival is not known. An important role has been attributed to the TNFR ligand, a proliferation-inducing ligand (APRIL), although the exact mechanism remained unclear. Since we detected that APRIL was expressed by CD68+ cells in CLL LN, we addressed its relevance in various aspects of CLL biology, using a novel APRIL overexpressing co-culture system, recombinant APRIL, and APRIL reporter cells. Unexpectedly, we found, that in these various systems, APRIL had no effect on survival of CLL cells, and activation of NF-kappaB was not enhanced on APRIL stimulation. Moreover, APRIL stity mulation did not affect CLL proliferation, neither as single stimulus nor in combination with known CLL proliferation stimuli. Furthermore, the survival effect conveyed by macrophages to CLL cells was not affected by transmembrane activator and CAML interactor-Fc, an APRIL decoy receptor. We conclude that the direct role ascribed to APRIL in CLL cell survival might be overestimated due to application of supraphysiological levels of recombinant APRIL. PMID- 27551514 TI - Cytotoxic L-amino-acid oxidases from Amanita phalloides and Clitocybe geotropa induce caspase-dependent apoptosis. AB - L-amino-acid oxidases (LAO) purified from fungi induce cell death in various mammalian cells including human tumor cell lines. The mechanism, however, remains poorly understood. In this study, we aimed to define a precise mechanism of cell death induced in Jurkat and MCF7 cancer cell lines by ApLAO and CgLAO, LAOs isolated from Amanita phalloides and Clitocybe geotropa, respectively. Cell death induced by both LAOs is shown to be concentration- and time-dependent, with higher toxic effects in Jurkat cells. LAO activity is required for the cytotoxicity. Detailed study on Jurkat cells further demonstrated that ApLAO and CgLAO both induce the intrinsic mitochondrial pathway of apoptosis, accompanied by a time-dependent depolarization of the mitochondrial membrane through the generation of reactive oxygen species. Treatment with the LAOs resulted in an increased ratio of the expression of proapoptotic Bax to that of antiapoptotic Bcl-2, subsequently leading to the activation of caspase-9 and -3. However, the pancaspase inhibitor, Z-VAD-FMK, did not completely abolish the cell death induced by either ApLAO or CgLAO, suggesting an alternative pathway for LAO induced apoptosis. Indeed, caspase-8 activity in ApLAO- and CgLAO-treated cells was increased. Further, Fas/FasL (Fas ligand) antagonist caused a slight reduction in toxin-induced cell death, supporting the involvement of ApLAO and CgLAO in death-receptor-mediated apoptosis. These results thus provide new evidence that ApLAO and CgLAO induce apoptosis in Jurkat cells via both the intrinsic and extrinsic pathways, although the significantly higher increase of caspase-9 over caspase-8 activity suggests that it is the intrinsic pathway that is the predominant mode of ApLAO- and CgLAO-induced apoptosis. PMID- 27551515 TI - Hypoxia and classical activation limits Mycobacterium tuberculosis survival by Akt-dependent glycolytic shift in macrophages. AB - Cellular reactive oxygen species (ROS) is a major antibacterial defense mechanism used by macrophages upon activation. Exposure of Mycobacterium tuberculosis (Mtb) infected macrophages to hypoxia is known to compromise the survival of the pathogen. Here we report that the hypoxia-induced control of intracellular Mtb load in RAW 264.7 macrophages was mediated by regulating the cellular ROS levels. We show that similar to classical activation, hypoxia incubation of macrophages resulted in decreased mitochondrial outer membrane potential (MOMP) and a concomitant increase in the cellular ROS levels. Mitochondrial depolarization and consequently higher ROS could be blocked by knocking down Akt using siRNAs, which acted by inhibiting the switch to glycolytic mode of metabolism, an essential adaptive response upon classical activation or hypoxic incubation of macrophages. Moreover, in the classically activated macrophages or in the macrophages under hypoxia incubation, supplementation with additional glucose had similar effects as Akt knockdown. Interestingly, in both the cases, the reversal of phenotype was linked with the ability of the mitochondrial F0-F1 ATP synthase activity to maintain the MOMP in the absence of oxidative phosphorylation. Both Akt knockdown and glucose supplementation were also able to rescue Mtb survival in these macrophages upon classical activation or hypoxia incubation. These results provide a framework for better understanding of how the interplay between oxygen supply, which is limiting in the human tubercular granulomas, and nutrient availability could together direct the outcome of infections in vivo. PMID- 27551516 TI - Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death. AB - The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex regulating key pathways in cell growth. Hyperactivation of mTORC1 is implicated in numerous cancers, thus making it a potential broad-spectrum chemotherapeutic target. Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. All treatments induced cleavage in the mTORC1 component, raptor, resulting in decreased raptor-mTOR interaction and subsequent inhibition of the mTORC1-mediated phosphorylation of downstream substrates (S6K and 4E-BP1). The cleavage was primarily mediated by caspase-6 and occurred at two sites. Mutagenesis at one of these sites, conferred resistance to cell death, indicating that raptor cleavage is important in chemotherapeutic apoptosis. PMID- 27551517 TI - Is low-protein diet a possible risk factor of malnutrition in chronic kidney disease patients? AB - Chronic kidney disease (CKD) is becoming increasingly widespread in the world. Slowing its progression means to prevent uremic complications and improve quality of life of patients. Currently, a low-protein diet (LPD) is one of the tools most used in renal conservative therapy but a possible risk connected to LPD is protein-energy wasting. The aim of this study is evaluate the possible correlation between LPD and malnutrition onset. We enrolled 41 CKD patients, stages IIIb/IV according to K-DIGO guidelines, who followed for 6 weeks a diet with controlled protein intake (recommended dietary allowance 0.7 g per kilogram Ideal Body Weight per day of protein). Our patients showed a significant decrease of serum albumin values after 6 weeks of LDP (T2) compared with baseline values (T0) (P=0.039), whereas C-reactive protein increased significantly (T0 versus T2; P=0.131). From body composition analysis, a significant impairment of fat-free mass percentage at the end of the study was demonstrated (T0 versus T2; P=0.0489), probably related to total body water increase. The muscular mass, body cell mass and body cell mass index are significantly decreased after 6 weeks of LDP (T2). The phase angle is significantly reduced at the end of the study compared with basal values (T0 versus T2; P=0.0001, and T1 versus T2; P=0.0015). This study indicated that LPD slows down the progression of kidney disease but worsens patients' nutritional state. PMID- 27551518 TI - Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer. AB - Colorectal cancer (CRC) is the second leading cause of cancer-related death in males and females in the world. It is of immediate importance to develop novel therapeutics. Human ribonucleotide reductase (RRM1/RRM2) has an essential role in converting ribonucleoside diphosphate to 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools. RRM2 is a prognostic biomarker and predicts poor survival of CRC. In addition, increased RRM2 activity is associated with malignant transformation and tumor cell growth. Bioinformatics analyses show that RRM2 was overexpressed in CRC and might be an attractive target for treating CRC. Therefore, we attempted to search novel RRM2 inhibitors by using a gene expression signature-based approach, connectivity MAP (CMAP). The result predicted GW8510, a cyclin-dependent kinase inhibitor, as a potential RRM2 inhibitor. Western blot analysis indicated that GW8510 inhibited RRM2 expression through promoting its proteasomal degradation. In addition, GW8510 induced autophagic cell death. In addition, the sensitivities of CRC cells to GW8510 were associated with the levels of RRM2 and endogenous autophagic flux. Taken together, our study indicates that GW8510 could be a potential anti-CRC agent through targeting RRM2. PMID- 27551520 TI - Erythrocyte glutathione transferase: a general probe for chemical contaminations in mammals. AB - Glutathione transferases (GSTs) are enzymes devoted to the protection of cells against many different toxins. In erythrocytes, the isoenzyme (e-GST) mainly present is GSTP1-1, which is overexpressed in humans in case of increased blood toxicity, as it occurs in nephrophatic patients or in healthy subjects living in polluted areas. The present study explores the possibility that e-GST may be used as an innovative and highly sensitive biomarker of blood toxicity also for other mammals. All distinct e-GSTs from humans, Bos taurus (cow), Sus scrofa (pig), Capra hircus (goat), Equus caballus (horse), Equus asinus (donkey) and Ovis aries (sheep), show very similar amino acid sequences, identical kinetics and stability properties. Reference values for e-GST in all these mammals reared in controlled farms span from 3.5+/-0.2 U/gHb in the pig to 17.0+/-0.9 U/gHb in goat; such activity levels can easily be determined with high precision using only a few microliters of whole blood and a simple spectrophotometric assay. Possibly disturbing factors have been examined to avoid artifact determinations. This study provides the basis for future screening studies to verify if animals have been exposed to toxicologic insults. Preliminary data on cows reared in polluted areas show increased expression of e-GST, which parallels the results found for humans. PMID- 27551519 TI - Transcription factor 7-like 1 dysregulates keratinocyte differentiation through upregulating lipocalin 2. AB - Recent studies strongly suggested that transcription factor 7-like 1 (Tcf7l1, also known as Tcf3) is involved in the differentiation of several types of cells, and demonstrated that Tcf7l1 modulates keratinocytes physiologically through regulating lipocalin 2 (LCN2), a key regulator of cell differentiation. To reveal the potential role of Tcf7l1 in the dysregulation of keratinocyte differentiation, both Tcf7l1 and LCN2 were determined in a variety of skin disorders. The in vitro effect of Tcf7l1 on keratinocyte differentiation was studied by culturing SCC-13 cells, and the human foreskin keratinocytes (HFKs) that were transfected with vectors for overexpressing human papillomavirus E6/E7 or Tcf7l1 genes. We found that both Tcf7l1 and LCN2 were highly expressed in those diseases characterized by defective keratinocyte differentiation (especially psoriasis vulgaris, condyloma acuminatum, squamous cell carcinoma, etc). Moreover, compared with control HFKs, SCC-13 cells and E6/E7-harboring HFKs expressed more Tcf7l1 and LCN2. Tcf7l1 siRNA transfection decreased LCN2 but increased involucrin and loricrin in HFKs under calcium stimuli. Conversely, Tcf7l1 overexpression in SCC-13 cells or vector-transfected HFKs induced lower involucrin and loricrin expression and less keratinocyte apoptosis, both of which, however, were partially abrogated by LCN2 siRNA or neutralizing anti-LCN2 antibody. Interestingly, the Tcf7l1 expression in HFKs correlated positively with the MMP-2 level, and the inhibition of MMP-2 decreased the LCN2 level and even attenuated the effect of Tcf7l1 on LCN2 expression. Therefore, Tcf7l1 dysregulates keratinocyte differentiation, possibly through upregulating the LCN2 pathway in an MMP-2 mediated manner. Elucidating the interaction between Tcf7l1 and LCN2 may help understand disordered cell differentiation in some skin diseases. PMID- 27551521 TI - Automatic quantitative analysis of experimental primary and secondary retinal neurodegeneration: implications for optic neuropathies. AB - Secondary neurodegeneration is thought to play an important role in the pathology of neurodegenerative disease, which potential therapies may target. However, the quantitative assessment of the degree of secondary neurodegeneration is difficult. The present study describes a novel algorithm from which estimates of primary and secondary degeneration are computed using well-established rodent models of partial optic nerve transection (pONT) and ocular hypertension (OHT). Brn3-labelled retinal ganglion cells (RGCs) were identified in whole-retinal mounts from which RGC density, nearest neighbour distances and regularity indices were determined. The spatial distribution and rate of RGC loss were assessed and the percentage of primary and secondary degeneration in each non-overlapping segment was calculated. Mean RGC number (82 592+/-681) and RGC density (1695+/ 23.3 RGC/mm(2)) in naive eyes were comparable with previous studies, with an average decline in RGC density of 71+/-17 and 23+/-5% over the time course of pONT and OHT models, respectively. Spatial analysis revealed greatest RGC loss in the superior and central retina in pONT, but significant RGC loss in the inferior retina from 3 days post model induction. In comparison, there was no significant difference between superior and inferior retina after OHT induction, and RGC loss occurred mainly along the superior/inferior axis (~30%) versus the nasal-temporal axis (~15%). Intriguingly, a significant loss of RGCs was also observed in contralateral eyes in experimental OHT. In conclusion, a novel algorithm to automatically segment Brn3a-labelled retinal whole-mounts into non-overlapping segments is described, which enables automated spatial and temporal segmentation of RGCs, revealing heterogeneity in the spatial distribution of primary and secondary degenerative processes. This method provides an attractive means to rapidly determine the efficacy of neuroprotective therapies with implications for any neurodegenerative disorder affecting the retina. PMID- 27551523 TI - Necroptosis DAMPens anti-tumor immunity. PMID- 27551522 TI - C-reactive protein levels in the perioperative period as a predictive marker of endoscopic recurrence after ileo-colonic resection for Crohn's disease. AB - The aim of this study was to determine the perioperative behavior of C-reactive protein (CRP) in Crohn's disease (CD) patients undergoing elective ileo-cecal (IC) resection and to identify association between perioperative CRP levels and endoscopic recurrence at 1 year. Study hypothesis was that perioperative CRP changes are disease specific and could detect subset of patients with more aggressive pathopysiology. Seventy-five patients undergoing IC resection for CD were prospectively enrolled. Serial CRP levels were assessed: preoperative, postoperative day 1 (POD1) and day 5 (POD5). CD patients' values were compared against same interval assessments of control groups undergoing right colectomy and appendicectomy. At POD1, the serum concentration increase was significantly higher in CD patients than in controls. Comparing with control groups, CRP levels remained remarkably high and showed a lower reduction in CD at POD5. Difference between groups was statistically significant. Optimal cutoff levels have been identified: serum CRP concentrations of >39.8 mg/l at POD1 and of >23.2 mg/l at POD5 have shown a significant association to endoscopic recurrence when using bivariate correlation. In this preliminary series, binary logistic regression could not demonstrate statistical relationship between endoscopic recurrence and any of the variables evaluated as prognostic factor. This is the only study so far that investigates and confirms a disease-specific upregulation of CRP response in the perioperative period for CD patients undergoing surgery. The postoperative CRP levels and kinetics seem to be related to the grade of mucosal inflammation and recurrence rate according to our 12 months endoscopic evaluation. PMID- 27551525 TI - Lifting the veil on fungal toxins. PMID- 27551524 TI - Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis. AB - Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of Staphylococcus aureus endophthalmitis and cultured human retinal Muller glia (MIO-M1 cell line), we demonstrate that S. aureus caused significant apoptotic cell death in the mouse retina and Muller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome c into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in S. aureus-infected retina/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in S. aureus infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP 1 (DPQ) inhibitors showed significant reduction in S. aureus-induced retinal cell death both in vivo and in vitro. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis. PMID- 27551526 TI - Class I HDAC inhibitor mocetinostat induces apoptosis by activation of miR-31 expression and suppression of E2F6. AB - The class I selective inhibitor of the histone deacetylases, mocetinostat, has promising antitumor activities in both preclinical studies and the clinical trials. To understand how mocetinostat induces apoptosis, we examined the effects of mocetinostat on miR-31, a proapoptotic microRNA that was previously found to be epigenetically silenced in prostate cancer. We found that miR-31 was significantly upregulated by mocetinostat in prostate cancer cells. Antiapoptotic protein E2F6, the target of miR-31, was decreased by mocetinostat treatment. When miR-31 was blocked with an inhibitor, the ability of mocetinostat to induce apoptosis was reduced. We further demonstrated that mocetinostat enhanced the activity of docetaxel in apoptosis induction. While siRNA knockdown of E2F6 sensitized cancer cells to mocetinostat-induced apoptosis, overexpression of E2F6 blocked mocetinostat-induced apoptosis. In an orthotopic xenograft model, we demonstrated that mocetinostat activated miR-31, decreased E2F6, induced apoptosis, and significantly reduced prostate cancer growth. Importantly, we found that mocetinostat also increased miR-31 expression, decreased E2F6, and induced apoptosis in the primary prostate cancer stem cells. Thus, activation of miR-31 and downregulation of E2F6 constitute an important mechanism in mocetinostat-induced apoptosis in prostate cancer. PMID- 27551527 TI - A NODding acquaintance with ER stress. PMID- 27551528 TI - Super-resolution microscopy reveals a golden kiss of death to mitochondria. PMID- 27551529 TI - Comparison of biological effects of modulated electro-hyperthermia and conventional heat treatment in human lymphoma U937 cells. AB - Loco-regional hyperthermia treatment has long history in oncology. Modulated electro-hyperthermia (mEHT, trade name: oncothermia) is an emerging curative treatment method in this field due to its highly selective actions. The impedance matched, capacitive-coupled modulated radiofrequency (RF) current is selectively focused in the malignant cell membrane of the cancer cells. Our objective is studying the cell-death process and comparing the cellular effects of conventional water-bath hyperthermia treatment to mEHT. The U937 human histiocytic lymphoma cell line was used for the experiments. In the case of conventional hyperthermia treatment, cells were immersed in a thermoregulated water bath, whereas in the case of mEHT, the cells were treated using a special RF generator (LabEHY, Oncotherm) and an applicator. The heating dynamics, the maximum temperature reached (42 degrees C) and the treatment duration (30 min) were exactly the same in both cases. Cell samples were analysed using different flow cytometric methods as well as microarray gene expression assay and western blot analysis was also used to reveal the molecular basis of the induced effects. Definite difference was observed in the biological response to different heat treatments. At 42 degrees C, only mEHT induced significant apoptotic cell death. The GeneChip analysis revealed a whole cluster of genes, which are highly up regulated in case of only RF heating, but not in conventional heating. The Fas, c Jun N-terminal kinases (JNK) and ERK signalling pathway was the dominant factor to induce apoptotic cell death in mEHT, whereas the cell-protective mechanisms dominated in case of conventional heating. This study has clearly shown that conventional hyperthermia and RF mEHT can result in different biological responses at the same temperature. The reason for the difference is the distinct, non-homogenous energy distribution on the cell membrane, which activates cell death-related signalling pathways in mEHT treatment but not in conventional heat treatment. PMID- 27551530 TI - Efficacy of PARP inhibition in Pde6a mutant mouse models for retinitis pigmentosa depends on the quality and composition of individual human mutations. AB - Retinitis pigmentosa (RP), an inherited blinding disease, is caused by a variety of different mutations that affect retinal photoreceptor function and survival. So far there is neither effective treatment nor cure. We have previously shown that poly(ADP-ribose)polymerase (PARP) acts as a common and critical denominator of cell death in photoreceptors, qualifying it as a potential target for future therapeutic intervention. A significant fraction of RP-causing mutations affect the genes for the rod photoreceptor phosphodiesterase 6A (PDE6A) subunit, but it is not known whether they all engage the same death pathway. Analysing three homozygous point mutations (Pde6a R562W, D670G, and V685M) and one compound heterozygous Pde6a (V685M/R562W) mutation in mouse models that match human RP patients, we demonstrate excessive activation of PARP, which correlated in time with the progression of photoreceptor degeneration. The causal involvement of PARP activity in the neurodegenerative process was confirmed in organotypic retinal explant cultures treated with the PARP-selective inhibitor PJ34, using different treatment time-points and durations. Remarkably, the neuroprotective efficacy of PARP inhibition correlated inversely with the strength of the genetically induced insult, with the D670G mutant showing the best treatment effects. Our results highlight PARP as a target for neuroprotective interventions in RP caused by PDE6A mutations and are a first attempt towards personalized, genotype-matched therapy development for RP. In addition, for each of the different mutant situations, our work identifies windows of opportunity for an optimal treatment regimen for further in vivo experimentation and possibly clinical studies. PMID- 27551531 TI - An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers. AB - Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality. PMID- 27551532 TI - The new editor-targeted genome engineering in the absence of homology-directed repair. PMID- 27551533 TI - A functional BH3 domain in an aquaporin from Leishmania infantum. AB - Despite the absence of sequences showing significant similarity to any of the members of the Bcl-2 family of proteins in protozoa, experiments carried out in yeast or trypanosomatids have demonstrated that ectopic expression of some of these members alters their response to different death stimuli. Because the BH3 domain is the smallest common signature in all the proteins of this family of apoptosis regulators and also because they are essential for molecular interactions between antagonistic members, we looked for sequences with significant similarity to the BH3 motif in the Leishmania infantum genome. Among the top scoring ones, we found the MYLALQNLGDEV amino-acid stretch at the C terminus of a previously described aquaporin, now renamed as Li-BH3AQP. This motif is highly conserved in homologous proteins from other species of the Leishmania genus. The association of Li-BH3AQP with human Bcl-XL was demonstrated by both co-immunoprecipitation and yeast two-hybrid experiments. Ectopic expression of Li-BH3AQP reduced viability of HeLa cells and this deleterious effect was abrogated by the simultaneous overexpression of Bcl-XL. Although we were not able to demonstrate a reduction in parasite viability when the protein was overexpressed in Leishmania promastigotes, a prodeath effect could be observed when the parasites overexpressing Li-BH3AQP were treated with staurosporine or antimycin A. Surprisingly, these parasites were more resistant, compared with wild-type parasites, to hypotonic stress or nutrient deprivation. The prodeath activity was abolished upon replacement of two highly conserved amino acids in this BH3 domain. Taken together, these results point to Li-BH3AQP as the first non-enzymatic protein ever described in trypanosomatids that is involved in cell death. PMID- 27551534 TI - Long-term neuroprotection of retinal ganglion cells by inhibiting caspase-2. PMID- 27551535 TI - Glucose- and glutamine-fueled stabilization of C-Myc is required for T-cell proliferation and malignant transformation. PMID- 27551537 TI - EGFRvIII: the promiscuous mutation. PMID- 27551536 TI - Bat-man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations. AB - Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans. PMID- 27551538 TI - Transcriptional landscapes at the intersection of neuronal apoptosis and substance P-induced survival: exploring pathways and drug targets. AB - A change in the delicate equilibrium between apoptosis and survival regulates the neurons fate during the development of nervous system and its homeostasis in adulthood. Signaling pathways promoting or protecting from apoptosis are activated by multiple signals, including those elicited by neurotrophic factors, and depend upon specific transcriptional programs. To decipher the rescue program induced by substance P (SP) in cerebellar granule neurons, we analyzed their whole-genome expression profiles after induction of apoptosis and treatment with SP. Transcriptional pathways associated with the survival effect of SP included genes encoding for proteins that may act as pharmacological targets. Inhibition of one of these, the Myc pro-oncogene by treatment with 10058-F4, reverted in a dose-dependent manner the rescue effect of SP. In addition to elucidate the transcriptional mechanisms at the intersection of neuronal apoptosis and survival, our systems biology-based perspective paves the way towards an innovative pharmacology based on targets downstream of neurotrophic factor receptors. PMID- 27551540 TI - Cardiac progenitor cells for heart repair. AB - Stem cell therapy is being investigated as an innovative and promising strategy to restore cardiac function in patients with heart failure. Several stem cell populations, including adult (multipotent) stem cells from developed organs and tissues, have been tested for cardiac repair with encouraging clinical and pre clinical results. The heart has been traditionally considered a post-mitotic organ, however, this view has recently changed with the identification of stem/progenitor cells residing within the adult heart. Given their cardiac developmental origins, these endogenous cardiac progenitor cells (CPCs) may represent better candidates for cardiac cell therapy compared with stem cells from other organs such as the bone marrow and adipose tissue. This brief review will outline current research into CPC populations and their cardiac repair/regenerative potential. PMID- 27551539 TI - Shp2 suppresses the adipogenic differentiation of preadipocyte 3T3-L1 cells at an early stage. AB - Tyrosine phosphatase protein Shp2 is a potential therapeutic target for obesity. However, the mechanism of Shp2 during adipogenesis is not fully understood. The present study investigated the role of Shp2 in the terminal differentiation of preadipocytes. The results showed that Shp2 suppressed adipocyte differentiation in 3T3-L1 cells; overexpression of Shp2 reduced lipid droplet production in 3T3 L1 cells, whereas Shp2 knockdown increased lipid droplet production in 3T3-L1 cells. Furthermore, inhibition of Shp2 activity also enhanced adipocyte differentiation. Interestingly, Shp2 expression was specifically decreased early during differentiation in response to stimulation with the dexamethasone methylisobutylxanthine-insulin (DMI) hormone cocktail. During the first 2 days of differentiation, Shp2 overexpression impaired the DMI-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in 3T3-L1 cells and blocked the peak expression of CCAAT/enhancer-binding proteins beta and delta during preadipocyte differentiation. In conclusion, Shp2 downregulated the early stages of hormone-induced differentiation of 3T3-L1 cells and inhibited the expression of the first wave of transcription factors by suppressing the DMI induced STAT3 signaling pathway. These discoveries point to a novel role of Shp2 during adipogenesis and support the hypothesis that Shp2 could be a therapeutic target for the control of obesity. PMID- 27551541 TI - Generating kidney tissue from pluripotent stem cells. AB - With the isolation of human pluripotent stem cells came the possibility of generating specific cell types for regenerative medicine. This has required the development of protocols for directed differentiation into many distinct cell types. One of the more complicated tissue types to recreate is the kidney. Here we review recent progress towards the recreation of not only specific kidney cell types but complex kidney organoids, models of the developing human organ, in vitro. We will also discuss potential short and long term applications of these approaches. PMID- 27551542 TI - Retinal pigment epithelial cell necroptosis in response to sodium iodate. AB - Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in the elderly in developed countries. The late stage of dry AMD, or geographic atrophy (GA), is characterized by extensive retinal pigment epithelium (RPE) degeneration. The underlying molecular mechanism for RPE cell death in GA remains unclear. Our previous study has established that RPE cells die predominantly from necroptosis in response to oxidative stress in vitro. Here, we extend our study and aim to characterize the nature of RPE cell death in response to sodium iodate (NaIO3) in vitro and in a NaIO3-induced retina degeneration mouse model. We found that NaIO3 induces RPE necroptosis in vitro by using a combination of molecular hallmarks. By using TUNEL assays, active caspase 3 and HMGB1 immunostaining, we confirmed that photoreceptor cells die mainly from apoptosis and RPE cells die mainly from necroptosis in response to NaIO3 in vivo. RPE necroptosis in this model is also supported by use of the RIPK1 inhibitor, Necrostatin-1. Furthermore, using novel RIPK3-GFP transgenic mouse lines, we detected RIPK3 aggregation, a hallmark of necroptosis, in the RPE cells in vivo after NaIO3 injection. Our findings suggest the necessity of re-evaluating RPE cell death mechanism in AMD models and have the potential to influence therapeutic development for dry AMD, especially GA. PMID- 27551544 TI - Life after death: RIP1 and RIP3 move beyond necroptosis. PMID- 27551543 TI - Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic. AB - As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms. PMID- 27551545 TI - The pro-oxidative drug WF-10 inhibits serial killing by primary human cytotoxic T cells. AB - Cytotoxic T-cells (CTLs) play an important role in many immune-mediated inflammatory diseases. Targeting cytotoxicity of CTLs would allow to interfere with immune-mediated tissue destruction. Here we demonstrate that WF-10, a pro oxidative compound, inhibits CTL-mediated cytotoxicity. WF-10 did not influence early steps of target-cell killing, but impaired the ability of CTLs to detach from the initial target cell and to move to a second target cell. This reduced serial killing was accompanied by stronger enrichment of the adhesion molecule LFA-1 in the cytolytic immune synapse. LFA-1 clustering requires activation of the actin-bundling protein L-plastin and was accordingly diminished in L-plastin knockdown cells. Interestingly, WF-10 likely acts through regulating L-plastin: (I) It induced L-plastin activation through phosphorylation leading to enhanced LFA-1-mediated cell adhesion, and, importantly, (II) WF-10 lost its influence on target-cell killing in L-plastin knockdown cells. Finally, we demonstrate that WF 10 can improve immunosuppression by conventional drugs. Thus, while cyclosporine A alone had no significant effect on cytotoxicity of CTLs, a combination of cyclosporine A and WF-10 blocked target-cell killing synergistically. Together, our findings suggest that WF-10 - either alone or in combination with conventional immunosuppressive drugs - may be efficient to control progression of diseases, in which CTLs are crucially involved. PMID- 27551547 TI - Long noncoding RNA LINP1: scaffolding non-homologous end joining. PMID- 27551546 TI - Precambrian origins of the TNFR superfamily. AB - The evolution of the tumor necrosis factor/tumor necrosis factor receptor superfamily (TNF/TNFR) is complicated and not well understood. To date, most TNFR studies have focused on vertebrate models leaving the role of TNFRs in invertebrates largely unexplored. The evolution of important cellular processes including stress response, apoptosis, development, and inflammation will be better understood by examining the TNF/TNFR superfamily in ancient invertebrate phyla. How widespread is this gene family within the evolutionary tree of life and is there evidence for similar function in invertebrates? A first step is to identify the presence or absence of these genes within basal metazoan taxa using the signature cysteine-rich domain (CRD) of the TNFR superfamily. In this perspective, we will start by examining what is currently known about the function of TNFRs in invertebrates. Then, we will assess the role of TNFRs in apoptosis and explore the origins of the domains found in TNFRs including the death domain (DD) and CRD. Finally, we will examine the phylogenetic relationship between TNFRs containing DDs identified to date. From these data, we propose a model for a Precambrian origin of TNFRs and their functional role in apoptosis. PMID- 27551548 TI - Supervisor types: which one is your match? PMID- 27551549 TI - Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer. AB - INTRODUCTION: The management of prostate cancer (PC) is still evolving. Although, androgen deprivation therapy (ADT) is an established treatment option, particularly in patients with disseminated disease, important data regarding hormonal manipulation have recently emerged. The aim of this paper is to review the evidence on ADT, make recommendations and address areas of controversy associated with its use in men with PC. MATERIAL AND METHODS: An expert panel was convened. Areas related to the hormonal management of patients with PC requiring evidence review were identified and questions to be addressed by the panel were determined. Appropriate literature review was performed and included a search of online databases, bibliographic reviews and consultation with experts. RESULTS: The panel was able to provide recommendations on: 1) which patients with localised PC should receive androgen deprivation in conjunction with radiotherapy (RT); 2) what standard initial treatment should be used in metastatic hormone naive PC (MHNPC); 3) efficacy of androgen deprivation agents; 4) whether ADT should be continued in patients with castration resistant PC (CRPC). However, no recommendations could be made for combined ADT and very high-dose RT in patients with an intermediate-risk disease. CONCLUSIONS: ADT remains the cornerstone of treatment for both metastatic hormone-naive and castration-resistant PC. According to the expert panel's opinion, based on the ERG report, luteinizing hormone-releasing hormone agonists might not be equivalent but this needs to be confirmed in long-term data. The combined use of ADT and RT improves outcome and survival in men with high-risk localised disease. The benefits in patients with intermediate-risk disease, particularly those subject to escalated dose RT are controversial. PMID- 27551551 TI - Review of current optical diagnostic techniques for non-muscle-invasive bladder cancer. AB - INTRODUCTION: Urinary bladder urothelial cell carcinoma is one of the most commonly diagnosed cancers in Europe. After prostate, lung and colon cancers, bladder cancer rates as the fourth most common cancer in men in the world. Urinary bladder cancer detection, treatment, and staging have traditionally been based on an endoscopic examination - cystoscopy. MATERIAL AND METHODS: A Medline, and Web of Science database search was performed on September 2015 without setting time limits, using the terms 'bladder cancer' in conjunction with 'cystoscopy', 'diagnosis', 'detection', 'fluorescence', 'blue-light', 'PDD', 'narrow band imaging', 'molecular imaging', 'optical coherence tomography' or 'confocal laser endomicroscopy'. RESULTS: The new imaging techniques can be classified according to their scope as macroscopic, microscopic, and molecular. Macroscopic techniques, such as narrow band imaging, are similar to white light cystoscopy; however, they help visualize even very minute lesions in the bladder mucosa by means of contrast enhancement. Microscopic imaging techniques, such as optical coherence tomography and confocal laser endomicroscopy, provide high resolution cross-sectional views of vesicular tissues, which resemble images obtained by histopathological examination. Therefore, these are referred as 'optical biopsy'. Molecular imaging methods offer highly specific real-time visualization of cancer cells and their differentiation from healthy tissue, by combining optical imaging with fluorescent labeling of elements such as antibodies. CONCLUSIONS: In this article we present a review of studies and literature concerning modern optical diagnostic techniques for non-muscle invasive bladder cancer. We present available technology with its advantages and disadvantages, and studies regarding its effectiveness. PMID- 27551550 TI - Vitamin D and urological cancers. AB - INTRODUCTION: Vitamin D controls calcium and phosphate homeostasis. Additionally, it has been proven that vitamin D is an important modulator of cellular differentiation and proliferation in a number of normal and malignant cells. Vitamin D can regulate proliferation, apoptosis, and cell adhesion at the tumor cell level. It also modifies tumor angiogenesis, invasion, and metastasis and also decreases oxidative DNA damage. MATERIAL AND METHODS: The Medline and Web of Science databases were searched without time limit on October 2015 using the terms 'vitamin D' in conjunction with 'kidney cancer', 'bladder cancer', 'prostate cancer', and 'testis cancer'. Autoalerts in Medline were also run and reference lists of original articles, review articles, and book chapters were searched for further eligible articles. RESULTS: In recent years, vitamin D has received vast attention due to suggestions that it may have a crucial role in the prevention and therapy of various cancers. Many epidemiologic studies have reported the impact of VD3 on preventing several cancers and other pathologies. Assuming that vitamin D status changes cancer risk, enough vitamin D supply would be an easy, economical, and safe cancer incidence and mortality reduction method. However, despite numerous researches, the role of vitamin D in cancer incidence and therapy remains unclear. CONCLUSIONS: The impact of vitamin D is well described in breast, colon, and prostate cancer; yet, there is only little published about other malignancies. PMID- 27551552 TI - Are we closer to seeing carcinoma in situ in the upper urinary tract? AB - INTRODUCTION: There is observed increase in detection rate of upper urinary tract urothelial cancer worldwide. This is a result of improved imaging as well as implementation of novel technologies of direct visualization of upper urinary tract. Standard techniques still remain insufficient to diagnose flat urothelial lesions. Carcinoma in situ is characterized by flat disordered proliferation of urothelial cells with marked cytologic abnormality, which occur within one cell layer as well as full thickness urothelium and therefore requires a better technology to pick up early and subtle mucosal changes. MATERIAL AND METHODS: The review presents available diagnostic tools in detection of upper urinary tract urothelial cancer and their ability to depict carcinoma in situ. RESULTS: Ureterorenoscopy is an investigation of choice as various promising techniques are under pilot investigations to enhance visualization of upper urinary tract carcinoma in situ. So far only photodynamic diagnosis has been reported to be as effective in detection of carcinoma in situ in the upper as within the lower urinary tract. CONCLUSIONS: Although we are close to see upper urinary tract carcinoma in situ all new promising diagnostic techniques still require further validation in multicenter clinical trials to indicate any change to current recommendations. PMID- 27551553 TI - Prostate MRI - an update for the referring urologist. AB - INTRODUCTION: Prostate MRI is a new and important tool which has a role in prostate cancer guidelines worldwide. The amount of articles published and studies currently taking place on the subject requires urologists to understand how the examination is performed and its possible applications. This article explains prostate MRI and standardized reporting schemes, as well as its applications according to patients' staging and history. MATERIAL AND METHODS: The use of prostate MRI prior to biopsy, MRI-guided biopsy and its use in active surveillance, surgery staging and planning, as well as in cases with biochemical recurrence are discussed. RESULTS: The application of prostate MRI are not limited to initial diagnosis, but also has a developing role in biopsy and planning further treatment. Recently, its diagnostic applications have been included in EAU prostate cancer guidelines and new applications are in development. CONCLUSIONS: Practicing urologists are seeing an emerging role of MRI in prostate cancer. Its current and future applications may have an impact on patient care, which mandates healthcare professionals to be vigilant about the method's new developments. PMID- 27551554 TI - Surgeon has a major impact on long-term recurrence risk in patients with non muscle invasive bladder cancer. AB - INTRODUCTION: One of the factors responsible for the risk of recurrence after complete transurethral resection of the bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) is the quality of surgery that may vary between individual surgeons. The aim of the study was to evaluate the impact of the surgeon on recurrence-free survival in patients with NMIBC. MATERIAL AND METHODS: The long-term results of a series of consecutive TURBTs performed by five staff urologists at a single institution were retrospectively analyzed. A total of 949 cases of organ-preserving treatment in 784 patients with NMIBC were included in the analysis. RESULTS: With the median follow-up of 64.3 months (3 124 months), the 5-year recurrence-free survival rates according to the surgeon were 62.9% (95% CI 56.2-69.7%), 53.6% (95% CI 47.4-59.9%), 51.0% (95% CI 39.6 62.4%), 46.2% (95% CI 36.4-56.0%), and 44.2% (95% CI 36.8-51.7%), respectively (p <0.0001). In the multivariate analysis including all potential risk factors, the individual surgeon was associated with a risk of recurrence with a high degree of statistical significance (p = 0.0013). The between-surgeon differences in the recurrence risk were not that pronounced in less extensive tumors. CONCLUSIONS: A surgeon has a significant impact on the risk of recurrence after curative treatment of patients with NMIBC. This effect was observed despite the relatively extensive experience in bladder endoscopic surgery of all of the surgeons and practicing in a setting of one specialized center. These findings should be taken into account while performing and evaluating the results of comparative studies. PMID- 27551555 TI - Comparative efficacy of tadalafil versus tamsulosin as the medical expulsive therapy in lower ureteric stone: a prospective randomized trial. AB - INTRODUCTION: In recent years, medical expulsive therapy has been used in the management of distal ureteric stones as a supplement to conservative treatment. Therefore, we conducted a prospective randomized study to evaluate the possible role of tadalafil individually in comparison with proven tamsulosin therapy in ureteric stone expulsion. The aim of this study is to compare the safety and efficacy of a phosphodiesterase-5 inhibitor (tadalafil) and an alpha-1 blocker (tamsulosin) as medical expulsive therapy for distal ureteric calculi. MATERIAL AND METHODS: Between August 2014 and October 2015, 207 patients who presented with distal ureteric stones of size 5-10 mm were randomly divided into two groups: tadalafil (Group A) and tamsulosin (Group B). Therapy was given for a maximum of 4 weeks. Stone expulsion rate, time to stone expulsion, analgesic use, number of hospital visits for pain, follow-up, endoscopic treatment and adverse effects of drugs were noted. Both groups were compared for normally distributed data by percentage, analysis of variance, and T-test. All the classified and categorical data were analyzed for both groups using the chi-square test. RESULTS: A statistically significant expulsion rate of 84.0% in Group A compared with 68.0% in Group B (P value = 0.0130), and shorter stone expulsion time in Group A (14.7+/-3.8) in comparison to Group B (16.8 +/-4.5) was observed. Statistically significant differences were noted in renal colic episodes and analgesic requirement in Group A than Group B. No serious adverse effects were noted. CONCLUSIONS: Tadalafil is safe, efficacious, and well tolerated as medical expulsive therapy for distal ureteric stones. This study showed that tadalafil increases ureteric stone expulsion quite significantly along with better control of pain and significantly lower analgesic requirement. PMID- 27551556 TI - Impact of ureteric stent on outcome of extracorporeal shockwave lithotripsy: A propensity score analysis. AB - INTRODUCTION: Extracorporeal shockwave lithotripsy (SWL) is one of the most frequently performed procedures in patients with urolithiasis. For ureter localized stones, SWL is often preceded by a double J stent insertion. However, fear of serious complications, including sepsis associated with stents, is often expressed. The following study assessed the impact of stent insertions on the results of SWL in patients with ureteric stones. MATERIAL AND METHODS: The study group consisted of 411 ureteric stone patients who were treated with SWL from January 2010 to December 2014. In 60 cases, treatment was preceded by ureteric stent insertion. A propensity scoring system was used to pair non-stented patients with the stented group. Success rates were assessed and compared using the chi-squared test. Multivariate logistic regression analysis was used to evaluate the influence of particular variables on the stone-free rate. RESULTS: The overall success rate was 82.2%. After matching, the success rate of the stented group was not significantly different from the control group (85.0% vs. 83.3% respectively, p = 0.80). The mean number of sessions was higher in the stented group (1.88 per patient). Stones located in the lower part of the ureter have the greatest chance of being successfully treated. CONCLUSIONS: The double J stent has no influence on the outcome of SWL treatment. In view of the greater likelihood of having additional sessions, this approach should be reserved for selected cases. PMID- 27551557 TI - Day care PNL using 'Santosh-PGI hemostatic seal' versus standard PNL: A randomized controlled study. AB - INTRODUCTION: To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. MATERIAL AND METHODS: It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. RESULTS: A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 +/-0.68 vs. 1.30 +/-0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 +/-1.23 vs. 6.12 +/-0.96, 1.48 +/ 0.50 vs. 4.09 +/-1.11 grams and 0.48 +/-0.26 vs. 4.74 +/-1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 +/-3.05 vs.18.42 +/-4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). CONCLUSIONS: Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission. PMID- 27551558 TI - A novel dosimeter for measuring the amount of radiation exposure of surgeons during percutaneous nephrolithotomy: InstadoseTM. AB - INTRODUCTION: The aim of this study was to demonstrate the efficacy of InstadoseTM, a novel dosimeter designed for radiation workers to provide a measurement of the radiation dose at any time from any computer; to determine the amount of radiation exposure during percutaneous nephrolithotomy (PNL); and to evaluate the factors that affect the amount of radiation exposed. MATERIAL AND METHODS: Two experienced surgeons wore InstadoseTM on the outer part of their lead aprons during the PNL procedures performed between December 2013 and July 2014. Patient demographics and stone characteristics were noted. Factors affecting radiation dose were determined. Fluoroscopic screening time was compared with the amount of radiation in order to validate the measurements of InstadoseTM. RESULTS: Overall, 51 patients with a mean age of 43.41 +/-18.58 (range 1-75) years were enrolled. Male to female ratio was 35/16. The amount of radiation was greater than 0.01mSv in only 19 (37.25%) cases. Stone location complexity (p = 0.380), dilation type (p = 0.584), stone size (p = 0.565), dilation size (p = 0.891) and access number (p = 0.268) were not associated with increased radiation exposure. InstadoseTM measurements were correlated with fluoroscopic screening time (r = 0.519, p = 0.001). CONCLUSIONS: InstadoseTM is a useful tool for the measurement of radiation exposure during PNL. The advantage of measuring the amount of radiation exposure after each PNL operation is that it may aid urologists in taking appropriate precautions to minimize the risk of radiation related complications. PMID- 27551559 TI - Quality of life in penile carcinoma patients - post-total penectomy. AB - INTRODUCTION: Total amputation, as a treatment for advanced penile cancer, significantly debilitates the patient's quality of life and sexual function. The aim of the study was to assess the quality of life in patients who had undergone total penectomy. MATERIAL AND METHODS: The questionnaires EORTC QLQ C-30, SES, CMNI, and a modified IIEF-15 questionnaire, were sent to 11 patients. RESULTS: A total of 10 patients returned the questionnaires completed. The results of the overall quality of life, the median result in individual domains, as assessed by the EORT QLQ C-30 questionnaire, were clearly lower than the reference results. There were statistically significant differences in the results of the QLQ C-30, concerning the role-functioning domain in relation to age (p = 0.008) and education (p = 0.032), in the domain of emotional functioning in relation to education (p = 0.008) and in the domains of physical functioning in relation to the partner relationship (p = 0.032). A significant number of patients were sexually inactive. Sexual activity as defined by touching the area of the pubic symphysis at the scars of the penis, touching and fondling perianal areas or the scrotum and watching things/people that cause excitement was observed in 2/10, 1/10 and 2/10 of patients respectively. In 5/6 of these patients, partnership relationships did not deteriorate, including one patient for whom the relationship actually improved. CONCLUSIONS: The results obtained indicate that total amputation of the penis significantly affects one's sex life and overall quality of life. However, this does not have negative implications in terms of partnership relations, self-assessment or the evaluation of masculinity. PMID- 27551561 TI - Long ureteric stricture replacement by buccal mucosa graft: an Armenian experience case series report. AB - INTRODUCTION: The aim of this study is to demonstrate the results of a case series concerning the replacement of long ureteric strictures using buccal mucosa grafts. MATERIAL AND METHODS: Five patients (3 men, 2 women), with a mean age of 35 years old, underwent reconstructive ureteral surgery using buccal mucosa graft with omental wrapping during the period of 2010-2013. In all cases, the location of strictures was in the proximal ureters with the length of strictures varying from 2.5 to 5.0 cm. RESULTS: We did not observe any major complications postoperatively. Two patients complained of constipation, which was resolved on the second day without any special treatment. Only one patient experienced fever (39 degrees C) on the seventh day after the surgery due to inadequate drainage of the nephrostomic tube. Mean follow-up time was 39.6 months (range 26-52 months), mean hospital stay length was 10.6 days. Intravenous and antegrade urography were performed after removing JJ stents. Results were favorable without any signs of stricture. Repetitive ultrasound and radiologic imaging was performed at month 3, 6, 12 in the first year and every half-year thereafter. Intravenous urography showed no signs of strictures. Hydronephrosis was resolved in all patients by the sixth month following the surgery. CONCLUSIONS: Postoperatively, we observed favorable results in all patients in terms of absence of short term-surgical complications. This technique could be considered for patients with long ureteric strictures in whom ureteral replacement with bowel interposition or kidney auto transplantation is contraindicated. PMID- 27551560 TI - Does inguinal hernia repair have an effect on sexual functions? AB - INTRODUCTION: The aim of this study is to evaluate sexual functions which are affected by inguinal hernias and may change after hernia repair surgery. MATERIAL AND METHODS: A total of 47 patients who underwent Lichtenstein tension-free anterior repair and inguinal hernia surgery were evaluated in terms of erectile function, intercourse function, sexual desire, overall satisfaction and orgasm satisfaction using the International Index of Erectile function questionnaire (IIEF) scoring system before surgery and in the first and sixth months after surgery. Parameters evaluated with the IIEF score before the surgery and in the first and sixth months after surgery were compared statistically using the Wilcoxon test. RESULTS: The average age of patients was 46.2 +/-11.2 years (range: 22-67). It was determined that all scores, apart from sexual desire (p = 0.08), significantly increased in the postoperative first and sixth months compared to the preoperative period. It was measured that the preoperative sexual desire score increased significantly in the postoperative sixth month (p <0.001). A significant score was also detected when all scores in the postoperative sixth month were compared to the postoperative first month. CONCLUSIONS: Inguinal hernia surgery positively affects sexual functions compared to the preoperative period. The improvement in sexual parameters in addition to the benefits of hernia removal and presence of no significant postoperative complications indicates that this surgery is useful and safe. PMID- 27551562 TI - Quality of life in young adult patients treated for bladder exstrophy. AB - INTRODUCTION: Bladder exstrophy (BE) is a rare condition that requires complex surgical corrections to achieve the goals of bladder functionality, normal sexual function, continence, and finally cosmesis. The purpose of this study was to identify clinical parameters that predict better quality of life (QOL) scores using a validated questionnaire (SF-36) with young adults after completing surgical reconstruction. MATERIAL AND METHODS: Forty-three young adults (mean age 22.35 years, 29 men and 14 women) treated for BE were evaluated using the Short Form 36 general health questionnaire (SF-36). Clinical assessment involved evaluation of the actual condition regarding continence, sexual function, genital satisfaction and overall cosmesis. RESULTS: Both genders presented similar QOL scores (p = 0.36). The QOL was not age-related (p = 0.63). Neither genders did not present any differences in the number of procedures (p = 0.27). Although no significant gender difference was found, clinical impairments - such as urinary fistula, incontinence, penile length and infertility - were associated with worse QOL scores and were male-related (p <0.01). The most common complaint after complete surgical repair was about penile length (26/29 patients, 89.6%). CONCLUSIONS: Age and gender were not predictors of better QOL scores. Any clinical impairment, such as urinary leakage due to incontinence or fistula, penile length and infertility, tended to significantly decrease the overall QOL in male patients with BE. The male genitalia seems to be the most troublesome aspect post-adolescence in treated male patients with exstrophy-epispadias. It has an important impact on the overall QOL, mainly having a social affect on those patients. PMID- 27551563 TI - Melatonin protects kidney against apoptosis induced by acute unilateral ureteral obstruction in rats. AB - INTRODUCTION: To investigate whether there was a protective effect of melatonin on apoptotic mechanisms after an acute unilateral obstruction of the kidney. MATERIAL AND METHODS: A total of 25 rats consisting of five groups were used in the study, designated as follows: Group 1: control, Group 2: sham, Group 3: unilateral ureteral obstruction treated with only saline, Group 4: unilateral ureteral obstruction treated with melatonin immediately, and Group 5: unilateral obstruction treated with melatonin one day after obstruction. Melatonin was administered as a 10 mg/kg dose intraperitoneally. The kidneys were evaluated according to the apoptotic index and Ki-67 scores. RESULTS: Comparison of all obstruction groups (Group 3, 4, and 5), revealed that the apoptotic index was significantly higher in Groups 1 and 2. Despite melatonin reduced apoptotic mechanisms in Groups 4 and 5, there was no significant difference between Groups 4 and 5 in terms of the reduction of apoptosis. However, the reduction of apoptosis in the melatonin treated group did not decrease to the level of Groups 1 and 2. CONCLUSIONS: Despite melatonin administration, which significantly reduces the apoptotic index occurring after acute unilateral ureteral obstruction, the present study did not observe a return to normal renal histology in the obstruction groups. PMID- 27551564 TI - Robotic genitalia sparing female cystectomy. PMID- 27551565 TI - Robotic intracorporeal studer pouch construction after genitalia preserving female cystectomy. PMID- 27551566 TI - Laparoscopic ultrasound assisted laparoscopic retroperitoneal schwannoma excision. PMID- 27551567 TI - Robotic-assisted bladder diverticulectomy. PMID- 27551568 TI - Low Levels of Hemoglobin at Admission Are Associated With Increased 30-Day Mortality in Patients With Hip Fracture. AB - INTRODUCTION: Previous smaller studies suggest that anemia is a risk factor for mortality in patients with hip fracture. The purpose of this investigation was to assess the correlation between hemoglobin at admission with 30-day mortality following a hip fracture in a large-scale study. PATIENTS AND METHODS: From January 1996 to December 2012, all patients with hip fracture (>60 years of age) admitted to Bispebjerg Hospital, Copenhagen, were identified from a local hip fracture database. We excluded conservatively treated patients and patients who died preoperatively. RESULTS: Seven thousand four hundred twenty-one consecutive patients with hip fracture were identified. Of those 7319 had a hemoglobin measurement on admission and were thus eligible for further analysis. Mean hemoglobin for patients alive at 30 days was 7.6 (standard deviation [SD]: 1.0) and for deceased patients 7.4 (SD: 1.1), P < .0001. Mean age was 82.6 years (SD: 8.5), and 76.5% of the population were female (Nfemales = 5600). The 30-day mortality decreases for every increase in hemoglobin of 1.0 mmol/L in a univariate analysis (P < .0001). The hazard ratio (HR) with 95% confidence interval (CI) for 30-day mortality in patients with anemia (<7.3 mmol/L for females and <8.3 mmol/L for males; Nanemic = 3235) was 1.66 (CI: 1.43-1.91, P < .0001). Adjusting for age, type of fracture, gender, and comorbidities (Charlson score) slightly attenuated the risk estimate (HR: 1.21, CI: 1.03-1.41, P = .02). CONCLUSION: This study demonstrates increased 30-day mortality in patients with low hemoglobin at admission, even after adjusting for comorbidities. PMID- 27551569 TI - Institutional Registry of Elderly Patients With Hip Fracture in a Community-Based Tertiary Care Hospital in Argentina (RIAFC). AB - BACKGROUND: A clinical registry encompasses a selective set of rigorously collected and stored clinical data focused on a specific condition. Hip fracture is a common complication of osteoporosis in elderly patients. Hip fracture substantially increases the risk of death and major morbidity in the elderly patients. Limited data regarding hip fracture are available from Latin America and Argentina. The purpose of this project is to create an institutional registry of elderly patients with hip fracture in order to obtain data that reveal the impact of this disease in our environment, allowing us to evaluate different strategies of patient's care and clinical outcomes. OBJECTIVE: To describe the implementation of an institutional registry of elderly patients with hip fracture in Argentina. METHODS: In this article, we described the creation, implementation, and data management of a prospective registry of elderly patients with hip fracture. The registry contains information on baseline demographics, comorbidities, laboratory, and radiological data. Follow-up at 3 and 12 months postfracture is done by phone interview to assess physical function, readmissions, and morbi-mortality. Clinical Trials registry number NCT02279550. CONCLUSION: In this project, we have created a hip fracture registry. We hope that this registry will provide valuable data that can lead us to new lines of research, addressed to answer questions raised in clinical practice. PMID- 27551570 TI - Tibial Plateau Fractures in Elderly Patients. AB - Tibial plateau fractures are common in the elderly population following a low energy mechanism. Initial evaluation includes an assessment of the soft tissues and surrounding ligaments. Most fractures involve articular depression leading to joint incongruity. Treatment of these fractures may be complicated by osteoporosis, osteoarthritis, and medical comorbidities. Optimal reconstruction should restore the mechanical axis, provide a stable construct for mobilization, and reestablish articular congruity. This is accomplished through a variety of internal or external fixation techniques or with acute arthroplasty. Regardless of the treatment modality, particular focus on preservation and maintenance of the soft tissue envelope is paramount. PMID- 27551571 TI - Evaluation of Contemporary Trends in Femoral Neck Fracture Management Reveals Discrepancies in Treatment. AB - BACKGROUND: Recent evidence supports total hip arthroplasty (THA) as compared to hemiarthroplasty (HA) for the management of displaced femoral neck fractures in a significant subset of elderly patients. The purpose of this study was to examine trends in femoral neck fracture management over the last 12 years. METHODS: Using the National Inpatient Sample database, we identified patients treated for femoral neck fractures between 1998 and 2010 with THA, HA, or internal fixation (IF). We examined treatment trends and demographic variables including patient age, gender, socioeconomic status, and payer and hospital characteristics. RESULTS: We identified 362 127 femoral neck fracture patients treated between 1998 and 2010. Overall, there were statistically significant increases in rates of THA and HA, whereas rates of IF decreased. Total hip arthroplasty varied based on patient age, with significant increases occurring in age-groups 0 to 49 years, 50 to 59 years, 60 to 69 years, and 70 to 79 years. Utilization of THA varied significantly based on socioeconomic status and race. Patient sex, urban versus rural hospital location, and teaching versus nonteaching hospital status were not related to rates of THA. CONCLUSION: Rates of THA for femoral neck fractures increased between 1998 and 2010 in patients younger than 80 years, suggesting that surgeons are responding to clinical evidence supporting THA for the treatment of elderly femoral neck fractures. This is the first study to demonstrate this change and expose disparities in practice patterns over time in response to this evidence in the United States. Further research is indicated to explore the effect of socioeconomic status and race on femoral neck fracture management. PMID- 27551572 TI - Do Total Knee Arthroplasty Patients Have a Higher Activity Level Compared to Patients With Osteoarthritis? AB - BACKGROUND: Despite the alleviation of osteoarthritis (OA) symptoms that total knee arthroplasty (TKA) provides for patients with end-stage knee OA, recent studies have suggested that TKA may not increase physical activity levels. In this study, we compare the physical activity levels of patients with OA treated nonoperatively (non-TKA) with both patients who had received TKA (post-TKA) and patients who received TKA within 3 years of data collection (pre-TKA). METHODS: Utilizing the Osteoarthritis Initiative database, accelerometry data were collected from non-TKA, pre-TKA, and post-TKA patients. Accelerometry data were subdivided by physical activity intensity levels, yielding daily minutes of each level of activity. Physical activity levels were then compared between non-TKA and pre-TKA/post-TKA patients. Physical activity levels for each patient were also compared to the Department of Health and Human Services (DHHS) guidelines for physical activity. RESULTS: There was no difference in physical activity between non-TKA and pre-TKA patients, with the exception of non-TKA patients achieving more daily minutes of vigorous activity (P < .001). There was no difference in physical activity between non-TKA and post-TKA patients. Although 11.6% of non-TKA patients met DHHS guidelines, only 4.8% of pre-TKA and 5.3% of post-TKA patients met guidelines. CONCLUSION: Despite the improvements in patient reported outcome measures following TKA, we found that TKA alone does not improve physical activity levels beyond those seen in the average patient with OA. In our study, the vast majority of patients with OA, treated nonoperatively or operatively, did not meet current DHHS guidelines for physical activity. PMID- 27551573 TI - Hypovitaminosis D Among Patients Admitted With Hip Fracture to a Level-1 Trauma Center in the Sunny Upper Egypt: Prevalence and Associated Correlates. AB - INTRODUCTION: Despite abundant sunshine, hypovitaminosis D is common in the Middle East. The aim of this study was to determine the prevalence of hypovitaminosis D and related correlates among patients with hip fracture in Assiut University Hospitals in Upper Egypt. MATERIALS AND METHODS: A cross sectional study was carried out in 133 patients with hip fracture, aged 50 years and older, admitted to Trauma Unit of Assiut University Hospitals, from January through December 2014. Patients were selected by systematic random sampling. Serum 25-hydroxy vitamin D level was measured by enzyme-linked immunosorbent assay; bone mineral density (BMD) by dual-energy X-ray absorptiometry. Weight and height measurements were used for body mass index (BMI) calculation. RESULTS: Patients' median age was 70 years (range: 50-99); 51.9% were females. Osteoporosis (femoral neck T score: <-2.5 standard deviation) prevalence was 72.2%. Of all patients, 60.9% had vitamin D deficiency (<20 ng/mL); 15.8% reported vitamin D inadequacy (from 20 to 29 ng/mL) and vitamin D levels were normal in 23.3% (>30 ng/mL). According to univariate analysis, vitamin D deficiency was significantly associated with obesity (P = .012) and low T scores of the femoral neck (P = .001), L2 (P = .021), L3 (P = .031), L4 (P = .012), and the greater trochanter (P < .001). In a multivariable logistic regression model, high BMI and low BMD of the femoral neck and greater trochanter were associated with hypovitaminosis D. CONCLUSION: Prevalence of hypovitaminosis D is high among patients with hip fracture and associated with low BMD and high BMI. Increasing awareness about prevention as well as detection and treatment of vitamin D deficiency is recommended. PMID- 27551574 TI - Different Stabilization Techniques for Type 62B3 Acetabular Fractures in Combination With Primary Total Hip Arthroplasty in Elderly Patients: A Biomechanical Comparison. AB - INTRODUCTION: The total hip arthroplasty (THA) as part of acute fracture management is used for acetabular fractures in elderly patients. Our objective was to assess the stability of osteosynthesis performed using 2 different techniques in combination with THA in an experimental model. MATERIALS AND METHODS: We conducted 20 experiments using the left-side hemipelves composite bone models. There were 2 testing groups: 1- and 2-stage osteosynthesis. The acetabular fractures of the anterior column and posterior hemitransverse were simulated. The same THA technique was used in both groups. The stability of osteosynthesis was explored and compared between the groups by measuring the fracture displacement of anterior and posterior columns under the standardized test load (1187 N) protocol. Load distance diagrams were generated. RESULTS: The 0.680-mm gap (0.518; 1.548) of the posterior column in the 1-stage group (n = 10) was higher than the 0.370-mm gap (0.255; 0.428) in the 2-stage group (n = 10; P = .002). There was no significant difference between the gap of the anterior column in the 1- and 2-stage groups (0.135 [0.078; 0.290] mm vs 0.160 [0.120; 0.210] mm; P = .579). CONCLUSION: The 2-stage osteosynthesis of the anterior and posterior columns in combination with THA provides better stability of posterior column when compared to 1-stage method in composite bone models. PMID- 27551575 TI - Patients With Multiple Myeloma Have More Complications After Surgical Treatment of Hip Fracture. AB - OBJECTIVES: Bone lesions from multiple myeloma may lead to pathological fracture of the proximal femur, requiring either fixation or arthroplasty. Little is known about the impact of multiple myeloma on hip fracture care. We investigated whether the patients with multiple myeloma undergoing surgical treatment of hip fractures would be at increased risk for adverse outcomes versus patients who sustain a hip fracture without multiple myeloma. METHODS: Using discharge records from the Nationwide Inpatient Sample (2002-2011), we identified 2 440 513 patients older than 50 years of age with surgically treated hip fractures. Of which, 4011 (0.2%) were found to have multiple myeloma. We compared perioperative outcomes between the patients with multiple myeloma and the nonmultiple myeloma patients using multivariable logistic regression modeling. RESULTS: Patients with multiple myeloma were more likely to have several postoperative complications, such as in-hospital pneumonia (odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.14-1.51), sepsis (OR: 1.72, 95% CI: 1.32-2.25), surgical site infection (OR: 1.66, 95% CI: 1.38-2.00), and acute renal failure (OR: 1.28, 95% CI: 1.14 1.43). We found that myeloma was not associated with increased inpatient mortality, myocardial infarction, respiratory failure, thromboembolic events, or pulmonary embolism. CONCLUSION: Patients with multiple myeloma are at increased risk for immediate postoperative complications following surgical treatment of hip fractures including in-hospital pneumonia, surgical site infection, and acute renal failure but not hospital mortality, when compared to hip fracture patients without multiple myeloma. Perioperative management of hip fractures in patients with myeloma may be optimized by increased awareness of these risks in this subset of patients. PMID- 27551576 TI - Management of Life-Threatening Arterial Hemorrhage Following a Fragility Fracture of the Pelvis in the Anticoagulated Patient: Case Report and Review of the Literature. AB - BACKGROUND: Life-threatening arterial bleeding from fragility fractures of the pelvis are very rare but associated with significant mortality, especially in anticoagulated patients. CASE DESCRIPTION: We report the successful interdisciplinary management of a 78-year-old woman under anticoagulation and antiplatelet therapy who had life-threatening arterial hemorrhage from the pubic rami following a fragility fracture of the pelvis. Our management strategy included early hemorrhage control by means of selective arterial embolization followed by surgical fracture stabilization and surgical hematoma evacuation. LITERATURE REVIEW: We identified 6 cases within the English literature, all involving females older than 70 years. All patients under anticoagulation developed hemorrhagic shock, and in 2 cases selective embolization contributed to survival of the patient. However, a combined management including fracture stabilization and hematoma evacuation has not been reported, allowing an excellent clinical outcome and discharge to geriatric rehabilitation. CLINICAL RELEVANCE: This case illustrates that elderly patients with apparently benign pelvic fragility fractures might develop severe hemorrhage due to arterial injury, especially when under dual anticoagulation, and stresses the importance of a high index of suspicion. If bleeding is suspected, detailed imaging studies are necessary to determine the source of bleeding and immediate angiographic or surgical interventions in combination with volume resuscitation and coagulation therapy should be readily available. PMID- 27551577 TI - Magnetic Resonance Imaging Diagnosis of Volvulus through Mesenteric Defect in Neonate. AB - Antenatal midgut volvulus is a rare surgical emergency in which bowel is severely compromised. Rarely the etiology is a mesenteric defect. Early diagnosis is essential and lifesaving in the immediate newborn period. Typically upper gastrointestinal or ultrasound imaging can be suggestive of the diagnosis of volvulus in the neonate. Sometimes, however, the diagnosis may be elusive. Herein, we report on the use of neonatal magnetic resonance imaging to diagnose a midgut volvulus that occurred through a congenital mesenteric defect. PMID- 27551578 TI - Topical Iodine-Induced Thyrotoxicosis in a Newborn with a Giant Omphalocele. AB - INTRODUCTION: Neonatal thyrotoxicosis is a life-threatening condition with potentially irreversible neurologic sequelae. Most cases are seen in neonates born to mothers with Graves' disease. Topical iodine-induced hypothyroidism has been reported in neonates, but iodine-induced neonatal hyperthyroidism has not been described; albeit a familiar entity in adults. CASE DESCRIPTION: Herein we present a unique case of a neonate, born with a giant omphalocele, who was treated with topical povidone-iodine dressings to promote escharification, in preparation for delayed surgical closure. By third day of life (DOL), the baby presented with a suppressed thyroid stimulating hormone of 0.59 uIU/mL, elevated free thyroxine of 5.63 ng/dL, and frank cardiovascular manifestations of thyrotoxicosis. After replacement of the topical iodine dressings with iodine free silver sulfadiazine, the thyroid status gradually improved with complete resolution of hyperthyroidism by 17th DOL. CONCLUSION: This case emphasizes that significant topical iodine exposure can result in both hypothyroidism and hyperthyroidism, and therefore, vigilance in monitoring thyroid function is imperative. PMID- 27551579 TI - Bilateral Pulmonary Agenesis: A Rare and Unexpected Finding in a Newborn. AB - BACKGROUND: Bilateral pulmonary agenesis is a rare congenital anomaly incompatible with life that can be missed on routine prenatal screening. Prenatal ultrasound diagnosis of this fatal anomaly can aid in prenatal counseling and postdelivery care. CASE STUDY: We report the case of a newborn who was born prematurely at 29 weeks gestation and underwent several unsuccessful intubation attempts immediately after delivery. CONCLUSION: Autopsy examination revealed bilateral pulmonary agenesis with a short, blindly ending trachea. PMID- 27551580 TI - Prophylactic Antibiotics in Twin Pregnancies Complicated by Previable Preterm Premature Rupture of Membranes. AB - OBJECTIVE: This study aims to determine if antibiotics given for latency to women with twins and previable preterm premature rupture of membranes (PPROM) affect the duration from membrane rupture to delivery. METHODS: A retrospective cohort study of twin pregnancies at a single center from 2000 to 2015 with previable (14 (0/7)-22 (6/7) weeks) PPROM was conducted. Women who were not candidates for expectant management or who elected for immediate delivery were excluded. Pregnancy complications, delivery data, and neonatal outcomes were compared between women who did and did not receive latency antibiotics. The primary outcome was latency. RESULTS: Of 52 eligible women, 30 (64%) elected expectant management; 17 women received antibiotics and 13 did not. No demographic differences existed between the groups. The median gestational age of rupture was 20 and 20.3 weeks in the antibiotic group and no antibiotic group, respectively. Median latency was 0.8 and 2.4 weeks in the antibiotic and no antibiotic groups correspondingly (p = 0.21). Overall, 58.8 and 23.1% of women who did and didn't receive antibiotics developed chorioamnionitis (p = 0.07). Perinatal mortality and maternal complication rates were high, though not different between the groups. CONCLUSION: Currently, even though in singletons with previable PPROM there is a recommendation to consider administrating antibiotics, in the setting of twins, no evidence exists to support this. PMID- 27551581 TI - Acute Myocardial Infarction in the First Trimester of Pregnancy in a Great Grand Multiparous Woman with Poorly Controlled Chronic Hypertension. AB - INTRODUCTION: Acute myocardial infarction (MI) in pregnancy is a rare event, usually occurring late in gestation, either in the third trimester or in the puerperium. It is associated with significant maternal and fetal morbidity and mortality. Although diagnosis and management of MI in pregnancy has been discussed in the literature, management of pregnancy following an early antepartum MI, which may have more consequences for the fetus, has not received as much attention. CASE: A 38-year-old great grand multiparous woman presented to the emergency department complaining of acute onset chest pain. The patient had a history of chronic hypertension and was an active smoker. She was incidentally found to be 5 weeks pregnant. She was diagnosed with an acute MI, which was treated by primary percutaneous coronary intervention. Her subsequent pregnancy course was complicated by poorly controlled chronic hypertension, but she ultimately delivered a healthy newborn at 36 weeks of gestational age. CONCLUSION: Good pregnancy outcomes are possible after early antepartum MI, especially with early diagnosis, appropriate treatment, and a multidisciplinary team approach to prenatal care. Delivery should occur in a tertiary referral center with experience managing high-risk obstetric patients with cardiac disease. PMID- 27551582 TI - High Resolution gamma-Ray Spectroscopy: the First 85 Years. AB - This opening review attempts to follow the main trends in crystal diffraction spectrometry of nuclear gamma rays from its 1914 beginning in Rutherford's laboratory to the ultra-high resolution instrumentation realized in the current generation of spectrometers at the Institute Laue Langeven (ILL). My perspective is that of an instrumentalist hoping to convey a sense of our intellectual debt to a number of predecessors, each of whom realized a certain elegance in making the tools that have enabled much good science, including that to which the remainder of this workshop is dedicated. This overview follows some of the main ideas along a trajectory toward higher resolution at higher energies, thereby enabling not only the disentangling of dense spectra, but also allowing detailed study of aspects of spectral profiles sensitive to excited state lifetimes and inter-atomic potentials. The parallel evolution toward increasing efficiency while preserving needed resolution is also an interesting story of artful compromise that should not be neglected. Finally, it is the robustness of the measurement chain connecting gamma-ray wavelengths with optical wavelengths associated with the Rydberg constant that only recently has allowed gamma-ray data to contribute to determination of particle masses and fundamental constants, as will be described in more detail in other papers from this workshop. PMID- 27551583 TI - Precision Measurement of Fundamental Constants Using GAMS4. AB - We discuss the connection of high-energy gamma-ray measurements with precision atomic mass determinations. These rather different technologies, properly combined, are shown to lead to new values for the neutron mass and the molar Planck constant. We then proceed to describe the gamma-ray measurement process using the GAMS4 facility at the Institut Laue-Langevin and its application to a recent measurement of the 2.2 MeV deuteron binding energy and the neutron mass. Our paper concludes by describing the first crystal diffraction measurement of the 8.6 MeV (36)Cl binding energy. PMID- 27551584 TI - The GRID Technique: Current Status and New Trends. AB - In the GRID technique one measures Doppler-broadened line profiles of gamma transitions using the high resolution crystal spectrometers GAMS, which are installed at the high flux reactor of the ILL Grenoble. One of the essential applications of this technique is the measurement of nuclear state lifetimes. In the present contribution the precision and the principal limits of the technique are discussed. PMID- 27551585 TI - Nuclear Structure-The Future With Radioactive Beams. AB - Some examples of new phenomena expected at extreme values of neutron and proton number are discussed, including soft dipole modes and neutron-proton pairing. First results on the N = Z nucleus (62)Ga are presented in the context of the competition between T = 0 and 1 states in odd-odd, self-conjugate nuclei. PMID- 27551586 TI - Low-Spin States From Decay Studies in the Mass 80 Region. AB - Neutron-deficient nuclei in the mass 80 region are known to exhibit strongly deformed ground states deduced mainly from yrast-state properties measured in beam via heavy-ion fusion-evaporation reactions. Vibrational excitations and non yrast states as well as their interplay with the observed rotational collectivity have been less studied to date within this mass region. Thus, several beta-decay experiments have been performed to populate low-spin states in the neutron deficient (80,84)Y and (80,84)Sr nuclei. An overview of excited 0(+) states in Sr and Kr nuclei is given and conclusions about shape evolution at low-spins are presented. In general, the non-yrast states in even-even Sr nuclei show mainly vibration-like collectivity which evolves to rotational behavior with increasing spin and decreasing neutron number. PMID- 27551587 TI - Precision Lifetime Measurements Using the Recoil Distance Method. AB - The recoil distance method (RDM) for the measurements of lifetimes of excited nuclear levels in the range from about 1 ps to 1000 ps is reviewed. The New Yale Plunger Device for RDM experiments is introduced and the Differential Decay Curve Method for their analysis is reviewed. Results from recent RDM experiments on SD bands in the mass-190 region, shears bands in the neutron deficient lead isotopes, and ground state bands in the mass-130 region are presented. Perspectives for the use of RDM measurements in the study of neutron-rich nuclei are discussed. PMID- 27551588 TI - Sub-Nanosecond Lifetime Measurement Using the Recoil-Distance Method. AB - The electromagnetic properties of low-lying nuclear states are a sensitive probe of both collective and single-particle degrees of freedom in nuclear structure. The recoil-distance technique provides a very reliable, direct and precise method for measuring lifetimes of nuclear states with lifetimes ranging from less than one to several hundred picoseconds. This method complements the powerful, but complicated, heavy-ion induced Coulomb excitation technique for measuring electromagnetic properties. The recoil distance technique has been combined with heavy-ion induced Coulomb excitation to study a variety of problems. Examples discussed are: study of the two-phonon triplet in (110)Pd, coupling of the beta and gamma degrees of freedom in (182,184)W, highly deformed gamma bands in (165)Ho, octupole collectivity in (96)Zr, and opposite parity states in (153)Eu. Consistency between the Coulomb excitation results and the lifetime measurements confirms the reliability of the complex analysis often encountered in heavy-ion induced Coulomb excitation work. PMID- 27551589 TI - Study of Interatomic Potentials Using the Crystal-GRID Method on Oriented Single Crystals of Ni, Fe, and Cr. AB - The Crystal-GRID method is used to study interatomic collisions at low energy in metals and such to probe the repulsive interatomic potential. Line shapes of gamma rays, emitted by the recoiling (59)Ni isotope after thermal neutron capture in Ni single crystals, were measured and compared to results obtained by molecular dynamics simulations of the slowing down. The same procedure is also used for recoiling (57)Fe and (54)Cr atoms in Fe and Cr single crystals, respectively. Different potentials (including several from the embedded atom method) are investigated using the observed fine structure of the line shape which depends on the crystal orientations. From the detailed study of the lineshapes measured in two different orientations, a new potential is then derived for each element. Nuclear state lifetimes for the excited isotopes are also deduced with a higher precision than obtained with standard nuclear techniques. PMID- 27551590 TI - Study of Interatomic Potentials in ZnS-Crystal-GRID Experiments Versus Ab Initio Calculations. AB - Crystal-GRID measurements have been performed with ZnS single crystals. For the first time, an asymmetric Crystal-GRID line shape could be observed. The preliminary data evaluation indicates that the reported lifetime of the 3221 keV level in (33)S is too short. A value of about 60 fs has been found. Due to this "long" lifetime the line shape is much less structured than calculated with the reported lifetime. PMID- 27551591 TI - Neutrino Induced Doppler Broadening. AB - When a nucleus undergoes beta decay via the electron capture reaction, it emits an electron neutrino. The neutrino emission gives a small recoil to the atom, which can be experimentally observed as a Doppler broadening on subsequently emitted gamma rays. Using the two-axis flat-crystal spectrometer GAMS4 and the electron capture reaction in (152)Eu, the motion of atoms having an excess kinetic energy of 3 eV in the solid state was studied. It is shown how the motion of the atom during the first hundreds of femtoseconds can be reconstructed. The relevance of this knowledge for a new neutrino helicity experiment is discussed. PMID- 27551592 TI - Current Topics in Gamma-Ray Astrophysics. AB - This paper reports on recent progress toward unraveling the origin of gamma-ray bursts. It is concluded that neutron-star binaries are one of the few remaining candidates. A model is proposed based upon general relativistic hydrodynamic studies which indicate a new physical process by which to power a gamma-ray burst. Relativistically driven compression, heating, and collapse of the individual neutron stars can occur many seconds before inspiral and merger. This compression may produce a neutrino burst of ~10(53) ergs lasting several seconds. The associated thermal neutrino emission produces an e (+)-e (-) pair plasma by [Formula: see text] annihilation. We show first results of a simulated burst which produces ~10(51) erg in gamma rays of the correct spectral and temporal properties. PMID- 27551593 TI - Nuclear Structure and Galactic gamma-Ray Activity. AB - The observation of galactic gamma lines following the decay of radioactive nuclei provides a direct link between nuclear physics experiments in earth-based laboratories and astrophysical observations with space-based observatories. Two examples are presented to illustrate this interplay: the measurement of the lifetime of (44)Ti to allow an improved determination of the (44)Ti mass of the supernova remnant Cassiopeia A from the observed gamma ray activity and the measurements of excited states in (24)Si to determine the reaction rate of (23)Al(p, gamma)(24)Si which might be important for a reduced production of (22)Na in novae. PMID- 27551594 TI - GRID and Multiphonon States. AB - The development of the GRID technique for determining nuclear level lifetimes of excited low-spin states populated in thermal neutron capture reactions has resulted in the ability to perform detailed studies of proposed multiphonon excitations for the first time. This paper discusses the experimental evidence for multiphonon excitations determined using the GRID technique. In deformed nuclei several good examples of gammagammaK(pi) = 4(+) excitations have been established, whereas the experimental evidence gathered on K(pi)= 0(+) bands is contradictory, and any interpretations will likely involve the mixing of several different configurations. In vibrational nuclei the GRID technique has helped to establish the existence of multiple quadrupole phonon excitations in (114)Cd, and an almost complete set of quadrupole-octupole coupled states in (144)Nd. PMID- 27551595 TI - Simulations of Gamma Cascades and Modelling Atomic Collision Chains. AB - A new method for simulation of nuclear gamma cascades by the Monte Carlo technique is described. It makes it possible to generate artificially individual events of the gamma-cascade decay of neutron capturing states in heavy nuclei. For the purpose of determination of lifetimes of nuclear levels by the GRID method the previously developed Mean Free Path Approach for modelling atomic collisions and their interplay with cascades has been generalized. Examples of the use of this generalization for determination of lifetimes of selected (150)Sm and (158)Gd levels are given and discussed. PMID- 27551596 TI - Lifetime Measurements in (178)Hf. AB - Lifetimes of levels from K(pi) = 2(+), K(pi) = 4(+) and several K(pi) = 0(+) bands have been measured in the (178)Hf nucleus using the GRID technique. Lifetimes of the 2(+) and 3(+) levels were measured within the K(pi) = 2(+) gamma band. A lower limit was established for the lifetime of the 4(+) level of the K(pi) = 4(+) band. The resulting upper limits for the absolute B(E2) values exclude collective transitions from the K(pi) = 4(+) to the ground state band but not to the K(pi)= 2(+) band. Level lifetimes were also measured for several states within three separate K(pi)= 0(+) bands. Evidence is presented for a previously unobserved case of two excited K(pi)= 0(+) bands being connected via collective E2 transitions. PMID- 27551597 TI - Magnetic Rotation in the A = 80 Region: M1 Bands in Heavy Rb Isotopes. AB - We have studied the isotopes (82)Rb45, (83)Rb46, and (84)Rb47 to search for magnetic rotation which is predicted in the tilted-axis cranking model for a certain mass region around A = 80. Excited states in these nuclei were populated via the reaction (11)B + (76)Ge with E = 50 MeV at the XTU tandem accelerator of the LNL Legnaro. Based on a gamma-coincidence experiment using the spectrometer GASP we have found magnetic dipole bands in each studied nuclide. The regular M1 bands observed in the odd-odd nuclei (82)Rb and (84)Rb include B(M1)/B(E2) ratios decreasing smoothly with increasing spin in a range of 13(-) <= J(pi) <= 16(-). These bands are interpreted in the tilted-axis cranking model on the basis of four-quasiparticle configurations of the type [Formula: see text]. This is the first evidence of magnetic rotation in the A ~ 80 region. In contrast, the M1 sequences in the odd-even nucleus (83)Rb are not regular, and the B(M1)/B(E2) ratios show a pronounced staggering. PMID- 27551598 TI - How Far From Stability Can We Go Using Gammasphere and the FMA? AB - This paper presents new results obtained using the U.S. national gamma-ray facility Gammasphere, which has been operating at the ATLAS accelerator at Argonne National Laboratory since January 1998. Gammasphere was built at Lawrence Berkeley Laboratory and used primarily as a powerful spectrometer for studying nuclei at the highest spins [1]. PMID- 27551599 TI - Nuclear Structure Studies With the Inelastic Neutron Scattering Reaction and Gamma-Ray Detection. AB - The (n,n'gamma) reaction has been used at the University of Kentucky accelerator facility to examine the detailed structure of a number of nuclei. The advantages of this method are reviewed, and recent developments are described. Examples of unique nuclear structure studies that have been carried out with this method are presented. PMID- 27551600 TI - Phonons and Phase Transitions in Finite Nuclei. AB - The nature and evolution of collectivity and coherence in nuclei is one of the most fundamental issues in nuclear structure and its evolution with N and Z. Despite many experiments, the nature of nuclear vibrational modes in deformed nuclei and the nature of nuclear phase/shape transitions are not at all understood. We discuss new experiments on phonon and multi-phonon states in the rare earth nuclei and on new evidence for phase coexistence in Sm that relates to the possible existence of phase transitional behavior in finite nuclei. PMID- 27551601 TI - Spectroscopy in the Second Minimum: Isotopic Limits, Lifetimes, and Magnetic Properties of Superdeformed Tl Nuclei. AB - In-beam gamma-ray spectroscopic studies of superdeformed bands in the mass 190 region are discussed with emphasis on recent results for Tl nuclei. Among those results, superdeformation at the edge of the region (in (189)Tl) and the first measurement of a superdeformed quadrupole moment in an odd-Z nucleus ((191)Tl) is presented. The experiments were conducted with the Gammasphere array at the Lawrence Berkeley National Laboratory. They are examples for the type of physics addressed in the first phase of Gammasphere operation. PMID- 27551602 TI - Nuclear Resonance Photon Scattering Studies of N 2 Adsorbed on Grafoil and of NaNO 2 Single Crystal. AB - The nuclear resonance photon scattering (NRPS) from (15)N2 adsorbed on graphite was investigated. The resonantly scattered intensities from the 6324 keV level of (15)N with the photon beam parallel and perpendicular to the adsorbing grafoil planes was measured at 140 K and coverages below 0.7 monolayers (ML), where the (15)N2 occur in the vapor phase. The data were used for deducing the out-of-plane tilt angle of adsorbed N2 relative to the graphite surface and the results were compared with grand canonical Monte Carlo (GCMC) calculations. Using the same method, a single crystal of NaNO2 was studied by measuring the scattering intensities with the nitrite planes aligned parallel and perpendicular to the photon beam. At 80 K, a huge anisotropy (R~3.6) was observed, caused by the anisotropy in the zero-point motion of the internal modes of vibration of the NO2 ion. The variation of the scattering intensity from a powdered isotopic (15)NaNO2 sample versus T in the range 12 K to 297 K was also measured and explained by accounting for the internal and external vibrational modes in NaNO2. PMID- 27551603 TI - GAMS5. AB - The construction of the double-crystal gamma-spectrometer GAMS5 was finished recently and the instrument is now operational. Measurements with double flat crystals were carried out and we will report here on the progress concerning the characteristics of the spectrometer. PMID- 27551604 TI - Secondary gamma Transitions in (159) Gd After Neutron Capture at Isolated Resonances. AB - The (158)Gd(n,gamma)(159)Gd reaction was studied at 12 isolated neutron resonances by the TOF method at the IBR-30 Fast Pulse Reactor at JINR Dubna. Totally 15 secondary gamma transitions in (159)Gd were recorded in the range from 450 keV to 750 keV. Of these, six previously unseen transitions were placed on the established (159)Gd level scheme. The depopulation of strongly populated levels at 507.7 keV and 558.2 keV (the head and the first excited members of band 1/2(-) [521]) was observed for the first time. It was shown that the observed 507.7 keV gamma line, masked by the annihilation peak, originates from an unresolved doublet of transitions from the 507.7 keV level to the ground state and from the 558.2 keV level to the level at 50.7 keV. The 507.7 keV level decays exclusively to the ground state, while the 558.2 keV level decays via two transitions with a branching ratio that agrees well with the prediction according to Alaga's rule. PMID- 27551605 TI - Application of GRID to Foreign Atom Localization in Single Crystals. AB - The application of GRID (Gamma Ray Induced Doppler broadening) spectroscopy to the localization of foreign atoms in single crystals is demonstrated on erbium in YAP. By the investigation of the Doppler broadened secondary gamma line for two crystalline directions, the Er was determined to be localized on the Y site. Conditions for the nuclear parameters of the impurity atoms used for the application of GRID spectroscopy are discussed. PMID- 27551606 TI - Noise-Optimized Silicon Radiometers. AB - This paper describes a new, experimentally verified, noise analysis and the design considerations of the dynamic characteristics of silicon radiometers. Transimpedance gain, loop gain, and voltage gain were optimized versus frequency for photodiode current meters measuring ac and dc optical radiation. Silicon radiometers with improved dynamic characteristics were built and tested. The frequency-dependent photocurrent gains were measured. The noise floor was optimized in an ac measurement mode using photodiodes of different shunt resistance and operational amplifiers with low 1/f voltage and current noise. In the dark (without any signal), the noise floor of the optimized silicon radiometers was dominated by the Johnson noise of the source resistance. The Johnson noise was decreased and equalized to the amplified 1/f input noise at a 9 Hz chopping frequency and 30 s integration time constant, resulting in an equivalent root-mean-square (rms) photocurrent noise of 8 * 10(-17) A. The lowest noise floor of 5 * 10(-17) A, equal to a noise equivalent power (NEP) of 1.4 * 10(-16) W at the 730 nm peak responsivity, was obtained at a 100 s integration time constant. The radiometers, optimized for ac measurements, were tested in a dc measurement mode as well. Performances in ac and dc measurement modes were compared. In the ac mode, a ten times shorter (40 s) overall measurement time was needed than in the dc mode (400 s) to obtain the same 10(-16) A noise floor. PMID- 27551607 TI - Absolute Steady-State Thermal Conductivity Measurements by Use of a Transient Hot Wire System. AB - A transient hot-wire apparatus was used to measure the thermal conductivity of argon with both steady-state and transient methods. The effects of wire diameter, eccentricity of the wire in the cavity, axial conduction, and natural convection were accounted for in the analysis of the steady-state measurements. Based on measurements on argon, the relative uncertainty at the 95 % level of confidence of the new steady-state measurements is 2 % at low densities. Using the same hot wires, the relative uncertainty of the transient measurements is 1 % at the 95 % level of confidence. This is the first report of thermal conductivity measurements made by two different methods in the same apparatus. The steady state method is shown to complement normal transient measurements at low densities, particularly for fluids where the thermophysical properties at low densities are not known with high accuracy. PMID- 27551608 TI - Thermal Conductivity of Saturated Liquid Toluene by Use of Anodized Tantalum Hot Wires at High Temperatures. AB - Absolute measurements of the thermal conductivity of a distilled and dried sample of toluene near saturation are reported. The transient hot-wire technique with an anodized tantalum hot wire was used. The thermal conductivities were measured at temperatures from 300 K to 550 K at different applied power levels to assess the uncertainty with which it is possible to measure liquid thermal conductivity over wide temperature ranges with an anodized tantalum wire. The wire resistance versus temperature was monitored throughout the measurements to study the stability of the wire calibration. The relative expanded uncertainty of the resulting data at the level of 2 standard deviations (coverage factor k = 2) is 0.5 % up to 480 K and 1.5 % between 480 K and 550 K, and is limited by drift in the wire calibration at temperatures above 450 K. Significant thermal-radiation effects are observed at the highest temperatures. The radiation-corrected results agree well with data from transient hot-wire measurements with bare platinum hot wires as well as with data derived from thermal diffusivities obtained using light-scattering techniques. PMID- 27551609 TI - Measurement of Calcium Activity in Oral Fluids by Ion Selective Electrode: Method Evaluation and Simplified Calculation of Ion Activity Products. AB - The activity of calcium in plaque fluid is needed to calculate the saturation level of that fluid relative to the tooth mineral. One method to determine the calcium activity in very small plaque fluid samples is by micro ion-selective electrode (ISE). Two commercially available calcium ionophores, a neutral-carrier and a charged-carrier, were evaluated in micro ISEs and compared to a commercially available macro ISE using saliva as a model for plaque fluid. The neutral-carrier containing ISEs gave results consistent with those of the macro ISE. Calcium activity measurements made with micro ISEs that contained the neutral ion-carrier of whole plaque samples and plaque fluid samples obtained by centrifugation of whole plaque showed that the activities did not change due to centrifugation. Estimates of the saturation with respect to hydroxyapatite were made from these measurements. A simplified calculation method is presented to estimate the ion activity product (IAP) of the calcium-phosphate minerals. The method is based on the relative abundance of some of the possible calcium-binding species and a fixed ionic strength for plaque fluid. Calculations show that within a normal pH range for plaque fluid (5.0 to 7.5) the differences in the IAP calculations for hydroxyapatite using the simplified method are less than those estimated from propagation of uncertainty calculations. PMID- 27551610 TI - Radioactivity Measurements on Glazed Ceramic Surfaces. AB - A variety of commonly available household and industrial ceramic items and some specialty glass materials were assayed by alpha pulse counting and ion chamber voltage measurements for radioactivity concentrations. Identification of radionuclides in some of the items was performed by gamma spectroscopy. The samples included tableware, construction tiles and decorative tiles, figurines, and other products with a clay based composition. The concentrations of radioactivity ranged from near background to about four orders of magnitude higher. Almost every nuclide identification test demonstrated some radioactivity content from one or more of the naturally occurring radionuclide series of thorium or uranium. The glazes seemed to contribute most of the activity, although a sample of unglazed pottery greenware showed some activity. Samples of glazing paints and samples of deliberately doped glass from the World War II era were included in the test, as was a section of foam filled poster board. A glass disc with known (232)Th radioactivity concentration was cast for use as a calibration source. The results from the two assay methods are compared, and a projection of sensitivity from larger electret ion chamber devices is presented. PMID- 27551611 TI - Electron-Impact Total Ionization Cross Sections of Molecular Ions. AB - The Binary-Encounter-Bethe (BEB) model for electron-impact total ionization cross sections of neutral molecules has been modified for molecular positive ions. The total ionization cross sections for [Formula: see text], [Formula: see text], CD(+), and CO(+) from the modified BEB formula are compared to available experimental data. The theory is in good agreement with experimental data on [Formula: see text], [Formula: see text], and CD(+), but the experimental data by Belic et al. on [Formula: see text], and CO(+) are lower than the theory. The large difference between the theory and experiment on CO(+) is a strong indication of the dominance of the dissociative ionization channel, CO(+) >C(+)+O(+), which was not included in the experiment. PMID- 27551612 TI - Radiative Calibration of Heat-Flux Sensors at NIST: Facilities and Techniques. AB - We present an overview of the National Institute of Standards and Technology high temperature blackbodies, both in operation and in development, suitable for heat flux sensor calibration. Typical results of calibrations using the transfer technique in the 25 mm Variable-Temperature Blackbody are presented to demonstrate the long-term repeatability of the calibration technique. A comparative study of the absolute and transfer calibrations of a Gardon gage in a spherical blackbody with a cooled enclosure surrounding the gage housing was conducted. Results of this study demonstrated the influence of convection associated with absolute calibration of sensors in a cooled enclosure. Plans for further development of the transfer technique to higher heat-flux levels and the associated technical issues are discussed. PMID- 27551613 TI - Treasure of the Past: I: RECOMPARISON OF THE UNITED STATES PROTOTYPE METER. PMID- 27551614 TI - IMPI: Making MPI Interoperable. AB - The Message Passing Interface (MPI) is the de facto standard for writing parallel scientific applications in the message passing programming paradigm. Implementations of MPI were not designed to interoperate, thereby limiting the environments in which parallel jobs could be run. We briefly describe a set of protocols, designed by a steering committee of current implementors of MPI, that enable two or more implementations of MPI to interoperate within a single application. Specifically, we introduce the set of protocols collectively called Interoperable MPI (IMPI). These protocols make use of novel techniques to handle difficult requirements such as maintaining interoperability among all IMPI implementations while also allowing for the independent evolution of the collective communication algorithms used in IMPI. Our contribution to this effort has been as a facilitator for meetings, editor of the IMPI Specification document, and as an early testbed for implementations of IMPI. This testbed is in the form of an IMPI conformance tester, a system that can verify the correct operation of an IMPI-enabled version of MPI. PMID- 27551615 TI - Technology Roadmaps for Compound Semiconductors. AB - The roles cited for compound semiconductors in public versions of existing technology roadmaps from the National Electronics Manufacturing Initiative, Inc., Optoelectronics Industry Development Association, Microelectronics Advanced Research Initiative on Optoelectronic Interconnects, and Optoelectronics Industry and Technology Development Association (OITDA) are discussed and compared within the context of trends in the Si CMOS industry. In particular, the extent to which these technology roadmaps treat compound semiconductors at the materials processing and device levels will be presented for specific applications. For example, OITDA's Optical Communications Technology Roadmap directly connects the information demand of delivering 100 Mbit/s to the home to the requirement of producing 200 GHz heterojunction bipolar transistors with 30 nm bases and InP high electron mobility transistors with 100 nm gates. Some general actions for progress towards the proposed International Technology Roadmap for Compound Semiconductors (ITRCS) and methods for determining the value of an ITRCS will be suggested. But, in the final analysis, the value added by an ITRCS will depend on how industry leaders respond. The technical challenges and economic opportunities of delivering high quality digital video to consumers provide concrete examples of where the above actions and methods could be applied. PMID- 27551616 TI - A Systematic Approach for Multidimensional, Closed-Form Analytic Modeling: Minority Electron Mobilities in Ga1-xAlxAs Heterostructures. AB - A significant, practical challenge, which arises in developing computationally efficient physical models for use in computer simulations of microelectronic and optoelectronic devices (for example, transistors in digital cellular phones and lasers in optical networks, respectively), is to represent vast amounts of numerical data for transport properties in two or more dimensions in terms of closed form analytic expressions. In this paper, we present a general methodology to achieve the above goal for a class of numerical data in a bounded two dimensional space. We then apply this methodology to obtain a closed-form analytic expression for the minority electron mobilities at 300 K in p-type Ga1- x Al x As as functions of the acceptor density N A between 10(16) cm(-3) and 10(20) cm(-3) and the mole fraction of AlAs x between 0.0 and 0.3. This methodology and its associated principles, strategies, regression analyses, and graphics are expected to be applicable to other problems beyond the specific case of minority mobilities addressed in this paper. PMID- 27551617 TI - Treasure of the Past: II: The Atomic Weight of Bromine. PMID- 27551618 TI - Using Impedance Spectroscopy to Assess the Viability of the Rapid Chloride Test for Determining Concrete Conductivity. AB - The suitability of using the initial current from the rapid chloride test (ASTM C 1202) to determine specimen conductivity is tested using impedance spectroscopy with a frequency spectrum of 10 Hz to 1 MHz. The specimen conductivity has an analytical relationship to specimen diffusivity and so is a useful quantity in service life prediction. Measurements made on specimens of different lengths indicate that the total charge passed during the six hour conduction test carried out according to ASTM C 1202 is not a direct measure of specimen conductivity. Further, ohmic heating during the 6 hour test makes it nearly impossible to directly measure any specimen transport property from the results. The total charge passed during the 6 hour conduction test is, therefore, not a reliable quantity for service life prediction. Results indicate that the direct current (dc) measurement of resistance using a voltage of 60 V is sufficient to overwhelm polarization effects, thereby yielding an accurate estimate of the true specimen conductivity. Impedance spectroscopy measurements also indicate that corrosion may form on the brass electrodes, adding bias to a conductivity estimate based upon a dc measurement. PMID- 27551619 TI - Capability in Rockwell C Scale Hardness. AB - A measurement system is capable if it produces measurements with uncertainties small enough for demonstration of compliance with product specifications. To establish the capability of a system for Rock-well C scale hardness, one must assess measurement uncertainty and, when hardness is only an indicator, quantify the relation between hardness and the product property of real interest. The uncertainty involves several components, which we designate as lack of repeatability, lack of reproducibility, machine error, and indenter error. Component-by-component assessment leads to understanding of mechanisms and thus to guidance on system upgrades if these are necessary. Assessment of some components calls only for good-quality test blocks, and assessment of others requires test blocks that NIST issues as Standard Reference Materials (SRMs). The important innovation introduced in this paper is improved handling of the hardness variation across test-block surfaces. In addition to hardness itself, the methods in this paper might be applicable to other local measurement of a surface. PMID- 27551620 TI - Massic Activity Ratios of the NBS/NIST Tritiated-Water Standards Issued Between 1954 and 1999. AB - As part of the preparation and calibration of three new National Institute of Standards and Technology (NIST) tritiated-water radioactivity Standard Reference Materials (SRMs), the massic-activity (activity of the sample divided by the mass of the sample) ratios of all of the available NBS/NIST tritiated-water SRMs issued between 1954 and 1999 were measured using liquid-scintillation (LS) counting. Four of the tritiated-water standards (SRMs 4361, 4926B, 4927C, and 4927D) were not available for measurement. All of the other tritiated-water standards (SRMs 4361B, 4361C, 4926, 4926C, 4926D, 4926E, 4927, 4927B, 4927E, and 4927F) were available, having been stored in flame-sealed glass ampoules. Where possible, massic-activity ratios measured by liquid-scintillation counting are compared with massic-activity ratios calculated from gravimetric dilution factors. The agreement is well within the stated uncertainties. For two of the tritiated-water standards that were not available for measurement (SRMs 4361 and 4926B), massic-activity ratios calculated from gravimetric dilution factors are available. PMID- 27551621 TI - Comprehensive Review and Critical Evaluation of the Half-Life of Tritium. AB - As part of the preparation and calibration of three new National Institute of Standards and Technology (NIST) tritiated-water radioactivity Standard Reference Materials (SRMs), we have performed a comprehensive review and critical evaluation of the half-life of tritium (hydrogen-3). Twenty three experimentally determined values of the half-life of tritium, reported between 1936 and 2000, were found. Six of these values were updated by later values. Two values were limits. Two values were deemed to be outliers. The 13 remaining values were evaluated in several ways. The results are compared with the results of other recent evaluations and all are found to be in good agreement. Our final recommended value for the half-life of tritium is the average of the adopted values from the four most recent evaluations, (4500 +/- 8) d, where 8 d corresponds to one standard uncertainty. PMID- 27551622 TI - Possible Advantages of a Robust Evaluation of Comparisons. AB - Mean values, traditionally used as a location parameter in the analysis of inter comparisons, are known to lack stability against the effect of "outliers". It is therefore proposed to replace (or complement) them by the use of medians, which have better statistical "robustness". An estimate for the corresponding uncertainty is derived and the procedure is illustrated by a numerical example. The simplicity of the suggested robust approach should favor its practical use in a number of metrological applications. PMID- 27551623 TI - Equations for the Magnetic Field Produced by One or More Rectangular Loops of Wire in the Same Plane. AB - Beginning with expressions for the vector potential, the equations for calculating the magnetic flux density from up to three rectangular loops of wire in the same plane are derived. The geometry considered is the same as that found in some walk-through metal detectors and electronic article surveillance systems. Equations for more or fewer loops can be determined by inspection. A computer program for performing the magnetic field calculation is provided in an appendix. PMID- 27551624 TI - An Auto-Focusing Method in a Microscopic Testbed for Optical Discs. AB - An auto-focusing method in a digital image system is demonstrated that uses a standard deviation of pixel gray levels as a feedback signal. In this system, an optical microscope and a charge coupled device (CCD) camera are used to create clear pit images of optical discs. A dynamic focusing scheme is designed in the system-control software, which is able to eliminate environmental disturbances and other noises so that a fast and stable focus can be achieved. The method shows an excellent focusing accuracy. The performance and possible applications of this method are discussed. The test results for optical discs are given in this paper. PMID- 27551625 TI - An Approach to Combining Results From Multiple Methods Motivated by the ISO GUM. AB - The problem of determining a consensus value and its uncertainty from the results of multiple methods or laboratories is discussed. Desirable criteria of a solution are presented. A solution motivated by the ISO Guide to the Expression of Uncertainty in Measurement (ISO GUM) is introduced and applied in a detailed worked example. A Bayesian hierarchical model motivated by the proposed solution is presented and compared to the solution. PMID- 27551626 TI - Numerical Evaluation of Diffraction Integrals. AB - This paper describes a simple numerical integration method for diffraction integrals which is based on elementary geometrical considerations of the manner in which different portions of the incident wavefront contribute to the diffracted field. The method is applicable in a wide range of cases as the assumptions regarding the type of integral are minimal, and the results are accurate even when the wavefront is divided into only a relatively small number of summation elements. Higher accuracies can be achieved by increasing the number of summation elements and/or incorporating Simpson's rule into the basic integration formula. The use of the method is illustrated by numerical examples based on Fresnel's diffraction integrals for circular apertures and apertures bounded by infinite straight lines (slits, half planes). In the latter cases, the numerical integration formula is reduced to a simple recursion formula, so that there is no need to perform repetitive summations for every point of the diffraction profile. PMID- 27551627 TI - Computation of Fresnel Integrals. II. AB - This paper describes an improved method for computing Fresnel integrals with an error of less than 1 * 10(-9). The method is based on a known approximate formula for a different integral which is due to Boersma and referenced by Abramowitz and Stegun. PMID- 27551628 TI - Thermal-Conductivity Apparatus for Steady-State, Comparative Measurement of Ceramic Coatings. AB - An apparatus has been developed to measure the thermal conductivity of ceramic coatings. Since the method uses an infrared microscope for temperature measurement, coatings as thin as 20 MUm can, in principle, be measured using this technique. This steady-state, comparative measurement method uses the known thermal conductivity of the substrate material as the reference material for heat flow measurement. The experimental method is validated by measuring a plasma sprayed coating that has been previously measured using an absolute, steady-state measurement method. The new measurement method has a relative standard uncertainty of about 10 %. The measurement of the plasma-sprayed coating gives 0.58 W.m(-1).K(-l) which compares well with the 0.62 W.m(-1).K(-l) measured using the absolute method. PMID- 27551629 TI - Treasure of the Past: III: Gravitational Anisotropy in Crystals. AB - Einstein's theory of gravitation is based upon a fundamental postulate which asserts that gravitation and inertia are identical in nature and hence indistinguishable. This if true, is of the greatest theoretical importance, for gravitation has heretofore refused to show any relationship to other physical phenomena. A most delicate test of this postulate is possible in a crystal of one of the nonisometric systems; for in such a crystal every known physical property (except inertia and, possibly, weight) varies with the axial direction in the crystal; and it is an interesting question whether, in such a crystal, gravitation will be found to align itself with inertia or will show some variability which will classify it with the great majority of physical phenomena. To test this point, large crystals were weighed in different axial positions with respect to the earth. The specimens examined represented all five nonisometric systems, and were weighed to a precision, in most cases, of 1 part in 10(9). The results were uniformly negative, and to this degree of precision are in Einstein's favor. Incidentally, this work has shown the practical possibility of using the gravity balance to a precision of I part in 10(9), even when the swing of the beam must.be stopped and the object turned through a considerable angle. A precision of about the same order was attained by Majorana in 1920. In this work it was not necessary to arrest the beam or to touch the load. The next best record (in work of a somewhat different kind) at the International Bureau of Weights and Measures is 7 parts in 10(9). PMID- 27551630 TI - Ab Initio Values of the Thermophysical Properties of Helium as Standards. AB - Recent quantum mechanical calculations of the interaction energy of pairs of helium atoms are accurate and some include reliable estimates of their uncertainty. We combined these ab initio results with earlier published results to obtain a helium-helium interatomic potential that includes relativistic retardation effects over all ranges of interaction. From this potential, we calculated the thermophysical properties of helium, i.e., the second virial coefficients, the dilute-gas viscosities, and the dilute-gas thermal conductivities of (3)He, (4)He, and their equimolar mixture from 1 K to 10(4) K. We also calculated the diffusion and thermal diffusion coefficients of mixtures of (3)He and (4)He. For the pure fluids, the uncertainties of the calculated values are dominated by the uncertainties of the potential; for the mixtures, the uncertainties of the transport properties also include contributions from approximations in the transport theory. In all cases, the uncertainties are smaller than the corresponding experimental uncertainties; therefore, we recommend the ab initio results be used as standards for calibrating instruments relying on these thermophysical properties. We present the calculated thermophysical properties in easy-to-use tabular form. PMID- 27551631 TI - Improved Near-Infrared Spectral Responsivity Scale. AB - A cryogenic radiometer-based system was constructed at the National Institute of Standards and Technology for absolute radiometric measurements to improve detector spectral power responsivity scales in the wavelength range from 900 nm to 1800 nm. In addition to the liquid-helium-cooled cryogenic radiometer, the system consists of a 100 W quartz-tungsten-halogen lamp light source and a 1 m single-grating monochromator for wavelength selection. The system was characterized and the uncertainty in spectral power responsivity measurements evaluated. A variety of photodetectors, including indium gallium arsenide photodiodes (InGaAs), germanium (Ge) photodiodes, and pyroelectric detectors, were subsequently calibrated. Over most of the spectral range, the spectral power responsivity of the photodetectors can be measured with a combined relative standard uncertainty of 0.4 % or less. This is more than a factor of two smaller than our previous capabilities, and represents a significant improvement in the near infrared (NIR) spectral power responsivity scale maintained at NIST. We discuss the characterization of the monochromator-based system and present results of photodetector spectral power responsivity calibrations. PMID- 27551632 TI - Comparison of the NIST and NPL Air Kerma Standards Used for X-Ray Measurements Between 10 kV and 80 kV. AB - A direct comparison was made between the air kerma primary standards used for the measurements of low-energy x rays at the National Institute of Standards and Technology (NIST) and the National Physical Laboratory (NPL). The comparison was conducted at the NPL using NPL reference radiation qualities between 10 kV and 80 kV. The results show the primary air-kerma standards to agree within 0.6 % of their values for beam qualities up to 80 kV. PMID- 27551633 TI - Material Properties of Titanium Diboride. AB - The physical, mechanical, and thermal properties of polycrystalline TiB2 are examined with an emphasis on the significant dependence of the properties on the density and grain size of the material specimens. Using trend analysis, property relations, and interpolation methods, a coherent set of trend values for the properties of polycrystalline TiB2 is determined for a mass fraction of TiB2 ? 98 %, a density of (4.5+/-0.1) g/cm(3), and a mean grain size of (9+/-1) um. PMID- 27551634 TI - Coding and Modulation for LMDS and Analysis of the LMDS Channel. AB - Local Multipoint Distribution Service (LMDS) has the potential to become a viable alternative to coaxial cable, fiber and other wired and wireless technologies providing "last mile" communication services. A major obstacle, however, is the high equipment cost. While for example cable modems supporting two-way services are available for $200 to $300, LMDS modem providing similar services will cost over $1000. The major cost driver of LMDS equipment is the radio frequency (RF) unit, as Ka-band technology still is quite expensive. The modem design must minimize the overall architecture cost, and low-cost modems requiring an expensive architecture should not be used. The channel characteristics of LMDS systems are very different from those of fiber, coaxial cable, and lower frequency wireless links, major channel impairments being non-linear high power amplifier (HPA), high phase noise and high co-channel interference. Modems should therefore be developed specifically for LMDS systems. This report deals with the choice of coding and modulation schemes, the LMDS channel, and how the channel impairments should be overcome by digital signal processing algorithms. PMID- 27551635 TI - Treasure of the Past: IV: THE STANDARD-CELL COMPARATOR, A SPECIALIZED POTENTIOMETER. AB - The standard cell plays a very important role in the maintenance of the electrical units and in correlating the units of the various national laboratories. Modern standard cells have attained such a high degree of reproducibility and permanence as to warrant the use of apparatus of the utmost precision and reliability in their intercomparison. The paper describes a new potentiometer developed especially for this purpose. Although it actually measures the small difference between the known emf of a reference cell and that of the cell under test, it contains a simple mechanical computing feature which automatically adds this small difference algebraically to the emf of the reference cell and thereby indicates directly the value of the emf under measurement. The design of the instrument is such that no readjustment of its coils will be required when the impending changes in the ohm and the volt are accomplished. The new instrument has been given the distinctive name, "standard cell comparator". PMID- 27551636 TI - Erratum: The NIST Length Scale Interferometer. AB - [This corrects the article on p. 225 in vol. 104.]. PMID- 27551637 TI - Erratum: Possible Advantages of a Robust Evaluation of Comparisons. AB - [This corrects the article on p. 551 in vol. 105.]. PMID- 27551638 TI - Opto-Mechanical and Electronic Design of a Tunnel-Trap Si Radiometer. AB - A transmission-type light-trap silicon radiometer has been developed to hold the NIST spectral power and irradiance responsivity scales between 406 nm and 920 nm. The device is built from replaceable input apertures and tightly packed different size silicon photodiodes. The photodiodes are positioned in a triangular shape tunnel such that beam clipping is entirely eliminated within an 8 field-of-view (FOV). A light trap is attached to the output of the radiometer to collect the transmitted radiation and to minimize the effect of ambient light. The photodiodes, selected for equal shunt resistance, are connected in parallel. The capacitance and the resultant shunt resistance of the device were measured and frequency compensations were applied in the feedback network of the photocurrent to-voltage converter to optimize signal-, voltage-, and loop-gain characteristics. The trap radiometer can measure either dc or ac optical radiation with high sensitivity. The noise-equivalent-power of the optimized device is 47 fW in dc mode and 5.2 fW at 10 Hz chopping. The relative deviation from the cosine responsivity in irradiance mode was measured to be equal to or less than 0.02 % within 5 degrees FOV and 0.05 % at 8 degrees FOV. The trap radiometer can transfer irradiance responsivities with uncertainties comparable to those of primary standard radiometers. Illuminance and irradiance meters, holding the SI units (candela, color- and radiance-temperature), will be calibrated directly against the transfer standard trap-radiometer to obtain improved accuracy in the base-units. PMID- 27551639 TI - External-Field Shifts of the (199)Hg(+) Optical Frequency Standard. AB - Frequency shifts of the (199)Hg(+) 5d (10)6s (2)S1/2 (F = 0, MF = 0) to 5d (9)6s (2 2)D5/2 (F = 2, MF = 0) electric-quadrupole transition at 282 nm due to external fields are calculated, based on a combination of measured atomic parameters and ab initio calculations. This transition is under investigation as an optical frequency standard. The perturbations calculated are the quadratic Zeeman shift, the scalar and tensor quadratic Stark shifts, and the interaction between an external electric field gradient and the atomic quadrupole moment. The quadrupole shift is likely to be the most difficult to evaluate in a frequency standard and may have a magnitude of about 1 Hz for a single ion in a Paul trap. PMID- 27551640 TI - Round Robin for Optical Fiber Bragg Grating Metrology. AB - NIST has administered the first round robin of measurements for optical fiber Bragg gratings. We compared the measurement of center wavelength, bandwidth, isolation, minimum relative transmittance, and relative group delay among several grating types in two industry groups, telecommunications and sensors. We found that the state of fiber Bragg grating metrology needs improvement in most areas. Specifically, when tunable lasers are used a filter is needed to remove broadband emissions from the laser. The linear slope of relative group delay measurements is sensitive to drift and systematic bias in the rf-modulation technique. The center wavelength measurement had a range of about 27 pm in the sensors group and is not adequate to support long-term structural monitoring applications. PMID- 27551641 TI - Calibration of High-Resolution X-Ray Tomography With Atomic Force Microscopy. AB - For two-dimensional x-ray imaging of thin films, the technique of scanning transmission x-ray microscopy (STXM) has achieved images with feature sizes as small as 40 nm in recent years. However, calibration of three-dimensional tomographic images that are produced with STXM data at this scale has not yet been described in the scientific literature, and the calibration procedure has novel problems that have not been encountered by x-ray tomography carried out at a larger scale. In x-ray microtomography, for example, one always has the option of using optical imaging on a section of the object to verify the x-ray projection measurements; with STXM, on the other hand, the sample features are too small to be resolved by light at optical wavelengths. This fact implies that one must rely on procedures with higher resolution, such as atomic force microscopy (AFM), for the calibration. Such procedures, however, generally depend on a highly destructive sectioning of the sample, and are difficult to interpret because they give surface information rather than depth information. In this article, a procedure for calibration is described that overcomes these limitations and achieves a calibration of an STXM tomography image with an AFM image and a scanning electron microscopy image of the same object. A Ge star shaped pattern was imaged at a synchrotron with a scanning transmission x-ray microscope. Nineteen high-resolution projection images of 200 * 200 pixels were tomographically reconstructed into a three-dimensional image. Features in two dimensional images as small as 40 nm and features as small as 80 nm in the three dimensional reconstruction were resolved. Transverse length scales based on atomic force microscopy, scanning electron microscopy, x-ray transmission and tomographic reconstruction agreed to within 10 nm. Toward the center of the sample, the pattern thickness calculated from projection images was (51 +/- 15) nm vs (80 +/- 52) nm for tomographic reconstruction, where the uncertainties are evaluated at the level of two standard deviations. PMID- 27551642 TI - Accelerating Scientific Discovery Through Computation and Visualization. AB - The rate of scientific discovery can be accelerated through computation and visualization. This acceleration results from the synergy of expertise, computing tools, and hardware for enabling high-performance computation, information science, and visualization that is provided by a team of computation and visualization scientists collaborating in a peer-to-peer effort with the research scientists. In the context of this discussion, high performance refers to capabilities beyond the current state of the art in desktop computing. To be effective in this arena, a team comprising a critical mass of talent, parallel computing techniques, visualization algorithms, advanced visualization hardware, and a recurring investment is required to stay beyond the desktop capabilities. This article describes, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing and visualization to accelerate condensate modeling, (2) fluid flow in porous materials and in other complex geometries, (3) flows in suspensions, (4) x ray absorption, (5) dielectric breakdown modeling, and (6) dendritic growth in alloys. PMID- 27551643 TI - Experimental Manufacture of Paper for War Maps. AB - Early in World War II, a new map paper was developed that greatly improved the quality and performance of war maps. The National Bureau of Standards cooperated in the development and, subsequently, determined by experimental manufacture how to make the paper from commercially available raw materials. The best results were obtained in experimental manufacture by using fiber furnishes of 100-percent strong bleached sulfate pulps with the addition of melamine-formaldehyde resin to increase the wet strength and titanium dioxide to produce the desired capacity. It was essential that the beating be very carefully controlled to preserve the maximum fiber strength. The most critical requirements from a manufacturing standpoint were very high resistance to tear, high wet tensile strength, high opacity, and good smoothness. A moderate degree of wildness was not objectionable. The data obtained by experiments were applied to initiate the commercial production of the new paper to meet unprecedented tonnage requirements. PMID- 27551644 TI - Erratum: Comparison of the NIST and NPL Air Kerma Standards Used for X-Ray Measurements Between 10 kV and 80 kV. AB - [This corrects the article on p. 701 in vol. 105.]. PMID- 27551645 TI - Comparative Study of Wavelet-Based Unsupervised Ocular Artifact Removal Techniques for Single-Channel EEG Data. AB - Electroencephalogram (EEG) is a technique for recording the asynchronous activation of neuronal firing inside the brain with non-invasive scalp electrodes. Artifacts, such as eye blink activities, can corrupt these neuronal signals. While ocular artifact (OA) removal is well investigated for multiple channel EEG systems, in alignment with the recent momentum toward minimalistic EEG systems for use in natural environments, we investigate unsupervised and effective removal of OA from single-channel streaming raw EEG data. In this paper, the unsupervised wavelet transform (WT) decomposition technique was systematically evaluated for the effectiveness of OA removal for a single-channel EEG system. A set of seven raw EEG data set was analyzed. Two commonly used WT methods, Discrete Wavelet Transform (DWT) and Stationary Wavelet Transform (SWT), were applied. Four WT basis functions, namely, haar, coif3, sym3, and bior4.4, were considered for OA removal with universal threshold and statistical threshold (ST). To quantify OA removal efficacy from single-channel EEG, five performance metrics were utilized: correlation coefficients, mutual information, signal-to artifact ratio, normalized mean square error, and time-frequency analysis. The temporal and spectral analysis shows that the optimal combination could be DWT with ST with coif3 or bior4.4 to remove OA among 16 combinations. This paper demonstrates that the WT can be an effective tool for unsupervised OA removal from single-channel EEG data for real-time applications. PMID- 27551646 TI - Design and Application of a New Automated Fluidic Visceral Stimulation Device for Human fMRI Studies of Interoception. AB - Mapping the brain centers that mediate the sensory-perceptual processing of visceral afferent signals arising from the body (i.e., interoception) is useful both for characterizing normal brain activity and for understanding clinical disorders related to abnormal processing of visceral sensation. Here, we report a novel closed-system, electrohydrostatically driven master-slave device that was designed and constructed for delivering controlled fluidic stimulations of visceral organs and inner cavities of the human body within the confines of a 3T magnetic resonance imaging (MRI) scanner. The design concept and performance of the device in the MRI environment are described. In addition, the device was applied during a functional MRI (fMRI) investigation of visceral stimulation related to detrusor distention in two representative subjects to verify its feasibility in humans. System evaluation tests demonstrate that the device is MR compatible with negligible impact on imaging quality [static signal-to-noise ratio (SNR) loss <2.5% and temporal SNR loss <3.5%], and has an accuracy of 99.68% for flow rate and 99.27% for volume delivery. A precise synchronization of the stimulus delivery with fMRI slice acquisition was achieved by programming the proposed device to detect the 5 V transistor-transistor logic (TTL) trigger signals generated by the MRI scanner. The fMRI data analysis using the general linear model analysis with the standard hemodynamic response function showed increased activations in the network of brain regions that included the insula, anterior and mid-cingulate and lateral prefrontal cortices, and thalamus in response to increased distension pressure on viscera. The translation from manually operated devices to an MR-compatible and MR-synchronized device under automatic control represents a useful innovation for clinical neuroimaging studies of human interoception. PMID- 27551647 TI - Health State Utilities for Patients with Brain Metastases. AB - PURPOSE: Estimating the cost-effectiveness of whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS), including Gamma Knife radiosurgery (GKRS), requires the quantitative measurement of patients' health states after treatment. We sought to quantify individuals' preferences for the relevant health states after WBRT or GKRS for brain metastases on a 0 to 1 scale, where 1 is perfect health and 0 is death. METHODS: We prospectively measured utilities in patients with brain metastases evaluated at Yale for consideration of WBRT and/or GKRS, as well as oncology nurses who had cared for patients with brain metastases before and after WBRT or GKRS, using the Standard Gamble (SG) technique. Demographic information was also collected. Nonparametric tests were used to compare potential differences in utility values and for subgroups based on demographic characteristics. RESULTS: There were 24 patients and 31 nurses who completed the study between December 2013 and May 2015. Median utilities ranged from 0.85 for the status-post (S/P) GKRS state to 0.25 (for neurologic dying). The median utility of being S/P WBRT was 0.70 compared to 0.85 S/P GKRS (p < 0.001). The cognitive decline from WBRT was associated with a notably low utility score of 0.30. There were no statistically significant differences between patients' and nurses' median utility scores. CONCLUSIONS: These SG utilities provide unique insights into brain metastases-related health states from the patient and provider perspective. As perceived by individuals with direct knowledge of the health states in question, WBRT has a significantly lower utility compared to GKRS. Cognitive decline following WBRT is associated with significant perceived reduction in quality of life. Differences in the relative importance of overall survival and quality of life with treatment existed between patients with different stages of disease. These utilities can be used to calculate quality-adjusted life expectancy in cost-effectiveness evaluations of SRS and WBRT. PMID- 27551648 TI - Lateral Thoracic Osteoplastic Rib-Sparing Technique Used for Lateral Spine Surgery: Technical Note. AB - Of patients who have undergone lateral approaches to the thoracic spine, surgical site postoperative pain appears to be greater among those who have undergone transection and removal of a rib segment than those who have not. Therefore, techniques that conserve anatomical position and minimize tissue disruption would theoretically result in less pain and a quicker recovery. Herein, we describe a rib-sparing osteoplastic technique used when rib segments need to be displaced in order to create an unobscured corridor to the operative target. Our approach minimizes soft tissue disruption and restores the anatomical function of the rib. Based on our experience, these patients report less pain, mobilize earlier, and are discharged sooner than those who have had rib segments sacrificed as part of a lateral approach to the spine. PMID- 27551649 TI - The Impact of Obesity on Patient Reported Outcomes Following Stereotactic Body Radiation Therapy for Prostate Cancer. AB - OBJECTIVES: The relationship between obesity (Body Mass Index ->30 kg/m(2)) and quality of life (QoL) following prostate cancer (PCa) radiation therapy (RT) is unknown. Excess abdominal fat may compromise the precise delivery of radiation, putting surrounding organs at risk for greater radiation exposure. Stereotactic body radiation therapy (SBRT) utilizes a real-time tracking system that provides updated prostate position information and allows for correction of the therapeutic beam during treatment with high accuracy. In this study, we evaluate the impact of obesity on patient reported outcomes following SBRT for prostate cancer. MATERIALS AND METHODS: Between February 2008 and April 2012, 88 obese and 178 non-obese patients with PCa were treated with SBRT at Georgetown University Hospital, Washington, DC. Health-related quality of life (HRQol) was assessed via the expanded prostate cancer index composite (EPIC)-26 at baseline, 6, 12, 18, and 24 months after 5-fraction delivery of 35-36.25 Gy with the CyberKnife. Patients who received androgen deprivation therapy (ADT) were excluded from this analysis due to its known negative impact on HRQoL. RESULTS: Pretreatment characteristics of obese and non-obese patient groups were similar except that obese patients had lower total testosterone levels. Urinary and bowel function and bother scores between the two patient cohorts were comparable at baseline and subsequent follow-ups. Sexual function and bother were also similar at baseline between both groups. Bother was defined by displeasure patients may experience from functional decline. At 24 months post-SBRT, obese men experienced borderline clinically significant decrease in sexual function and greater sexual bother compared to non-obese patients. Fatigue was significantly higher in obese patients compared to non-obese patients at 18 months post-SBRT. CONCLUSIONS: Prostate SBRT affects obese and non-obese patients similarly in total HRQoL scores and majority of its domains. Obesity has been associated with cancer recurrence; therefore longer follow-up is required to determine the impact of obesity on cancer control. PMID- 27551650 TI - Superseding the Hourglass Effect Toward the Successful Commercialization of Nanotechnology in the Medical Sciences - We Require a Change in Perspective. AB - Nanotechnology and, specifically, nanomedicine has been touted as the next breakthrough technology for medical sciences. Although there are large advances being seen in the preclinical phases of development, there is still a paucity of viable and effective nanomedicine technologies in the clinical setting. We attempt to provide some suggestions as to the stumbling blocks of meaningful translation of this technology from the bench to the bedside. We give due consideration to the role of evidence-based medicine, regulatory pathways, and the commercialization efforts of nanomedicine at various stages in playing key roles in moving this technology into clinical use. PMID- 27551651 TI - Lumbosacral Osteomyelitis and Discitis with Phlegmon Following Laparoscopic Sacral Colpopexy. AB - Lumbosacral osteomyelitis and discitis are usually a result of hematogenous spread; rarely it can result from direct inoculation during a surgical procedure. Bacteria may also track along implanted devices to a different location. This is a rare complication seen from pelvic organ prolapse surgery with sacral colpopexy. A 67-year-old female developed increasing lower back pain four months following a laparoscopic sacral colpopexy. Imaging revealed lumbar 5-sacral 1 (L5 S1) osteomyelitis and discitis with associated phlegmon confirmed by percutaneous biopsy and culture. The patient was treated conservatively with antibiotics, but required laparoscopic removal of the pelvic and vaginal mesh followed by twelve weeks of intravenous antibiotics. The patient has experienced clinical improvement of her back pain. This is an uncommon complication of sacral colpopexy, but physicians must be vigilant and manage aggressively to avoid more serious complications and permanent deficit. PMID- 27551652 TI - Ultrasound-Assisted Distal Radius Fracture Reduction. AB - Introduction Closed reduction of distal radius fractures (CRDRF) is a commonly performed emergency department (ED) procedure. The use of point-of-care ultrasound (PoCUS) to diagnose fractures and guide reduction has previously been described. The primary objective of this study was to determine if the addition of PoCUS to CRDRF changed the perception of successful initial reduction. This was measured by the rate of further reduction attempts based on PoCUS following the initial clinical determination of achievement of best possible reduction. Methods We performed a multicenter prospective cohort study, using a convenience sample of adult ED patients presenting with a distal radius fracture to five Canadian EDs. All study physicians underwent standardized PoCUS training for fractures. Standard clinically-guided best possible fracture reduction was initially performed. PoCUS was then used to assess the reduction adequacy. Repeat reduction was performed if deemed indicated. A post-reduction radiograph was then performed. Clinician impression of reduction adequacy was scored on a 5 point Likert scale following the initial clinically-guided reduction and following each PoCUS scan and the post-reduction radiograph. Results There were 131 patients with 132 distal radius fractures. Twelve cases were excluded prior to analysis. There was no significant difference in the assessment of the initial reduction status by PoCUS as compared to the clinical exam (mean score: 3.8 vs. 3.9; p = 0.370; OR 0.89; 95% CI 0.46 to 1.72; p = 0.87). Significantly fewer cases fell into the uncertain category with PoCUS than with clinical assessment (2 vs 12; p = 0.008). Repeat reduction was performed in 49 patients (41.2%). Repeat reduction led to a significant improvement (p < 0.001) in the PoCUS determined adequacy of reduction (mean score: 4.3 vs 3.1; p < 0.001). In this group, the odds ratio for adequate vs. uncertain or inadequate reduction assessment using PoCUS was 12.5 (95% CI 3.42 to 45.7; p < 0.0001). There was no significant difference in the assessment of reduction by PoCUS vs. radiograph. Conclusions PoCUS-guided fracture reduction leads to repeat reduction attempts in approximately 40% of cases and enhances certainty regarding reduction adequacy when the clinical assessment is unclear. PMID- 27551653 TI - Stability of Programmable Shunt Valve Settings with Simultaneous Use of the Optune Transducer Array: A Case Report. AB - The Optune(r) transducer array (Novocure Ltd., Haifa, Israel) is an FDA-approved noninvasive regional therapy that aims to inhibit the growth of glioblastoma multiforme (GBM) cells via utilization of alternating electric fields. Some patients with GBM may develop hydrocephalus and benefit from subsequent shunt placement, but special attention must be paid to patients in whom programmable valves are utilized, given the potential effect of the magnetic fields on valve settings. We present the first case report illustrating the stability of programmable shunt valve settings in a neurosurgical patient undergoing therapy with the Optune device. In this study, shunt valve settings were stable over a period of five days despite Optune therapy. This is reassuring for patients with GBM who require simultaneous treatment with both the Optune device and a programmable shunt system. PMID- 27551654 TI - Barriers to Real-Time Medical Direction via Cellular Communication for Prehospital Emergency Care Providers in Gujarat, India. AB - BACKGROUND: Many low- and middle-income countries depend on emergency medical technicians (EMTs), nurses, midwives, and layperson community health workers with limited training to provide a majority of emergency medical, trauma, and obstetric care in the prehospital setting. To improve timely patient care and expand provider scope of practice, nations leverage cellular phones and call centers for real-time online medical direction. However, there exist several barriers to adequate communication that impact the provision of emergency care. We sought to identify obstacles in the cellular communication process among GVK Emergency Management and Research Institute (GVK EMRI) EMTs in Gujarat, India. METHODS: A convenience sample of practicing EMTs in Gujarat, India were surveyed regarding the barriers to call initiation and completion. RESULTS: 108 EMTs completed the survey. Overall, ninety-seven (89.8%) EMTs responded that the most common reason they did not initiate a call with the call center physician was insufficient time. Forty-six (42%) EMTs reported that they were unable to call the physician one or more times during a typical workweek (approximately 5-6 twelve-hour shifts/week) due to their hands being occupied performing direct patient care. Fifty-eight (54%) EMTs reported that they were unable to reach the call center physician, despite attempts, at least once a week. CONCLUSION: This study identified multiple barriers to communication, including insufficient time to call for advice and inability to reach call center physicians. Identification of simple interventions and best practices may improve communication and ensure timely and appropriate prehospital care. PMID- 27551655 TI - Preoperative Testosterone Therapy Prior to Surgical Correction of Hypospadias: A Review of the Literature. AB - Hypospadias is a congenital anomaly of the male urethra that causes significant morbidity in the pediatric male population. The mainstay of treatment is hypospadias repair surgery. However, given the common co-occurrence of microphallus in these patients, surgery remains difficult without adequate tissue for proper reconstruction of the urethra. The use of preoperative testosterone therapy, parenterally or topically, has been a topic of study for several years in urologic literature. This literature review aims to summarize the different studies that have been conducted to address whether preoperative testosterone therapy is beneficial, inconsequential, or detrimental to the surgical and cosmetic outcomes of hypospadias repair as well as to address the differences in routes of administration. PMID- 27551656 TI - Precise methane absorption measurements in the 1.64 MUm spectral region for the MERLIN mission. AB - In this article we describe a high-precision laboratory measurement targeting the R(6) manifold of the 2nu3 band of 12CH4. Accurate physical models of this absorption spectrum will be required by the Franco-German, Methane Remote Sensing LIDAR (MERLIN) space mission for retrievals of atmospheric methane. The analysis uses the Hartmann-Tran profile for modeling line shape and also includes line mixing effects. To this end, six high-resolution and high signal-to-noise absorption spectra of air-broadened methane were recorded using a frequency stabilized cavity ring-down spectroscopy apparatus. Sample conditions corresponded to room temperature and spanned total sample pressures of 40 hPa - 1013 hPa with methane molar fractions between 1 MUmol mol-1 and 12 MUmol mol-1. All spectroscopic model parameters were simultaneously adjusted in a multispectrum nonlinear least-squares fit to the six measured spectra. Comparison of the fitted model to the measured spectra reveals the ability to calculate the room-temperature, methane absorption coefficient to better than 0.1% at the on line position of the MERLIN mission. This is the first time that such fidelity has been reached in modeling methane absorption in the investigated spectral region, fulfilling the accuracy requirements of the MERLIN mission. We also found excellent agreement when comparing the present results with measurements obtained over different pressure conditions and using other laboratory techniques. Finally, we also evaluated the impact of these new spectral parameters on atmospheric transmissions spectra calculations. PMID- 27551657 TI - Development of Hierarchical Polymer@Pd Nanowire-Network: Synthesis and Application as Highly Active Recyclable Catalyst and Printable Conductive Ink. AB - A facile one-pot approach for preparing hierarchical nanowire-networks of hollow polymer@Pd nanospheres is reported. First, polymer@Pd hollow nanospheres were produced through metal-complexation-induced phase separation with functionalized graft copolymers and subsequent self-assembly of PdNPs. The nanospheres hierarchically assembled into the nanowire-network upon drying. The Pd nanowire network served as an active catalyst for Mizoroki-Heck and Suzuki-Miyaura coupling reactions. As low as 500 MUmol % Pd was sufficient for quantitative reactions, and the origin of the high activity is ascribed to the highly active sites originating from high-index facets, kinks, and coalesced structures. The catalyst can be recycled via simple filtration and washing, maintaining its high activity owing to the micrometer-sized hierarchical structure of the nanomaterial. The polymer@Pd nanosphere also served as a printable conductive ink for a translucent grid pattern with excellent horizontal conductivity (7.5*10(5) S m(-1)). PMID- 27551658 TI - Core-Substituted Naphthalenediimides: LUMO Levels Revisited, in Comparison with Preylenediimides with Sulfur Redox Switches in the Core. AB - Core-substituted naphthalenediimides (NDIs) attract increasing attention to bind, transport, and transform electrons, anions, anionic intermediates, and anionic transition states, and to shine as most colorful rainbow fluorophores. The energy level of their lowest unoccupied molecular orbital (LUMO) is decisive for many of these applications. Here, differential pulse voltammetry (DPV) measurements for a consistent series of NDIs are reported to extract exact LUMO levels under identical conditions. The influence of primary and secondary substituents in the core and on the primary imides is compared with general trends for the reliable prediction of LUMO levels in functional systems. Emphasis is on sulfur redox switches in the NDI core because of their frequent use as isostructural probes for pi acidity. The same sulfur redox chemistry is expanded to perylenediimides (PDIs), and LUMO engineering is discussed in a broader context, including also fullerenes, aminonaphthalimides (ANIs), and aminoperyleneimides (APIs). The result is a comprehensive reference table that graphically maps out the LUMO space covered by the leading families of electronaccepting aromatics. This graphical summary of general trends in the pi-acidic space is expected to be both inspiring and quite useful in practice. PMID- 27551659 TI - Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues. AB - A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5'-O-tritylated and the 5'-O-dimethoxytritylated 5 fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5'O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at MUm concentrations, however significantly weaker potency against YFV. PMID- 27551660 TI - Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism. AB - We have analyzed the structure and bonding of gas-phase Cl-X and [HCl-X](+) complexes for X(+)= H(+), CH3 (+), Li(+), and Na(+), using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl(-) and HCl for the various cations. The Cl-X bond becomes longer and weaker along X(+) = H(+), CH3 (+), Li(+), and Na(+). Our main purpose is to understand the heterolytic bonding mechanism behind the intrinsic (i.e., in the absence of solvent) alkali metal cation affinities (AMCA) and how this compares with and differs from those of the proton affinity (PA) and methyl cation affinity (MCA). Our analyses are based on Kohn-Sham molecular orbital (KS-MO) theory in combination with a quantitative energy decomposition analysis (EDA) that pinpoints the importance of the different features in the bonding mechanism. Orbital overlap appears to play an important role in determining the trend in cation affinities. PMID- 27551661 TI - Enzymatic Strategy for the Resolution of New 1-Hydroxymethyl Tetrahydro-beta carboline Derivatives in Batch and Continuous-Flow Systems. AB - Many alkaloids containing a tetrahydro-beta-carboline skeleton have well-known therapeutic effects, leading to increased interest in the synthesis of these natural products. Enantiomers of N-Boc-protected 1-hydroxymethyl-1,2,3,4 tetrahydro-beta-carboline [(+/-)-7], 1-hydroxymethyl-6-methoxy-1,2,3,4-tetrahydro beta-carboline [(+/-)-8], and 1-hydroxymethyl-6-fluoro-1,2,3,4-tetrahydro-beta carboline [(+/-)-9] were prepared through enzymecatalyzed asymmetric acylation of their primary hydroxyl group. The preliminary experiments were performed in a continuous-flow system, while the preparative-scale resolutions were done as batch reactions. Excellent enantioselectivities (E>200) were obtained with Candida antarctica lipase B (CAL-B) and acetic anhydride in toluene at 60 degrees C. The recovered alcohols and the produced esters were obtained with high enantiomeric excess values (ee>=96 %). The O-acylated enantiomers [(S)-10-(S) 12)] were transformed into the corresponding amino alcohols [(S)-7-(S)-9)] with methanolysis. Microwave-assisted Boc removals were also performed and resulted in the corresponding compounds (R)-4-(R)-6 and (S)-4-(S)-6 without a drop in the enantiomeric excess values (ee>=96 %). PMID- 27551662 TI - Systematic Studies on 3 d- and 4 f-Metal Containing Polyoxometalates Suitable for Organic Derivatization. AB - Premium polyoxometalates! The organic functionalization of 3 d-metalsubstituted polyoxometalates and the synthesis of new metal-oxo clusters with accessible 3 d- and 4 f-metal centers suitable for organic derivatization are discussed in this thesis. A total number of 39 compounds were structurally characterized, and their luminescent and magnetic properties analyzed. The solution behavior was studied by NMR spectroscopy, mass spectrometry, and light-scattering techniques. PMID- 27551663 TI - Corrigendum: Sterically Demanding Unsymmetrical Diaryl-lambda(3)-iodanes for Electrophilic Pentafluorophenylation and an Approach to alpha-Pentafluorophenyl Carbonyl Compounds with an All-Carbon Stereocenter. AB - [This corrects the article DOI: 10.1002/open.201402045.]. PMID- 27551664 TI - Open Steps: A journey to discover and document Open Knowledge projects around the globe. PMID- 27551665 TI - Impaired causal awareness and associated cortical-basal ganglia structural changes in youth psychiatric disorders. AB - BACKGROUND: Cognitive impairments contribute significantly to disease burden in young individuals presenting with major psychiatric disorders. The capacity to encode the consequences of one's actions may be of particular importance for real world functioning due to its fundamental role in goal-directed behavior. METHODS: Here, we investigated a dimensional measure of causal awareness during a probabilistic learning task in 92 young individuals with an admixture of major mood and psychotic illnesses, at early and more established stages. Using automated gray matter segmentation of T1-weighted images, we estimated the volume and shapes of major subcortical structures and investigated their association with causal awareness. RESULTS: The low causal awareness (LCA) group (n = 35) reported increased social disability (p = .004) and reduced right pallidal size, specifically within the dorsolateral surfaces (p = .02), relative to the unimpaired high causal awareness (HCA) patients (n = 57). In early-stage illness, LCA had a smaller right thalamus (p = .002) relative to HCA. Exploratory investigations suggested that in developed psychotic syndromes, causal awareness was correlated with left hippocampal size (p = .006) whereas, in more persistent affective disorders, causal awareness was correlated with left amygdala size (p = .013), specifically within the anterior aspect. DISCUSSION: Low causal awareness occurs across diagnoses and stages of illness and is associated with poor functional outcomes. Our results suggest that there may be shared neural underpinnings of its dysfunction in the early course of mood and psychotic disorders, however in more established illness, there is greater neurobiological divergence in causal awareness correlates between diagnoses. PMID- 27551666 TI - PREVAIL: Predicting Recovery through Estimation and Visualization of Active and Incident Lesions. AB - OBJECTIVE: The goal of this study was to develop a model that integrates imaging and clinical information observed at lesion incidence for predicting the recovery of white matter lesions in multiple sclerosis (MS) patients. METHODS: Demographic, clinical, and magnetic resonance imaging (MRI) data were obtained from 60 subjects with MS as part of a natural history study at the National Institute of Neurological Disorders and Stroke. A total of 401 lesions met the inclusion criteria and were used in the study. Imaging features were extracted from the intensity-normalized T1-weighted (T1w) and T2-weighted sequences as well as magnetization transfer ratio (MTR) sequence acquired at lesion incidence. T1w and MTR signatures were also extracted from images acquired one-year post incidence. Imaging features were integrated with clinical and demographic data observed at lesion incidence to create statistical prediction models for long term damage within the lesion. VALIDATION: The performance of the T1w and MTR predictions was assessed in two ways: first, the predictive accuracy was measured quantitatively using leave-one-lesion-out cross-validated (CV) mean-squared predictive error. Then, to assess the prediction performance from the perspective of expert clinicians, three board-certified MS clinicians were asked to individually score how similar the CV model-predicted one-year appearance was to the true one-year appearance for a random sample of 100 lesions. RESULTS: The cross-validated root-mean-square predictive error was 0.95 for normalized T1w and 0.064 for MTR, compared to the estimated measurement errors of 0.48 and 0.078 respectively. The three expert raters agreed that T1w and MTR predictions closely resembled the true one-year follow-up appearance of the lesions in both degree and pattern of recovery within lesions. CONCLUSION: This study demonstrates that by using only information from a single visit at incidence, we can predict how a new lesion will recover using relatively simple statistical techniques. The potential to visualize the likely course of recovery has implications for clinical decision-making, as well as trial enrichment. PMID- 27551667 TI - Synchrony of auditory brain responses predicts behavioral ability to keep still in children with autism spectrum disorder: Auditory-evoked response in children with autism spectrum disorder. AB - The auditory-evoked P1m, recorded by magnetoencephalography, reflects a central auditory processing ability in human children. One recent study revealed that asynchrony of P1m between the right and left hemispheres reflected a central auditory processing disorder (i.e., attention deficit hyperactivity disorder, ADHD) in children. However, to date, the relationship between auditory P1m right left hemispheric synchronization and the comorbidity of hyperactivity in children with autism spectrum disorder (ASD) is unknown. In this study, based on a previous report of an asynchrony of P1m in children with ADHD, to clarify whether the P1m right-left hemispheric synchronization is related to the symptom of hyperactivity in children with ASD, we investigated the relationship between voice-evoked P1m right-left hemispheric synchronization and hyperactivity in children with ASD. In addition to synchronization, we investigated the right-left hemispheric lateralization. Our findings failed to demonstrate significant differences in these values between ASD children with and without the symptom of hyperactivity, which was evaluated using the Autism Diagnostic Observational Schedule, Generic (ADOS-G) subscale. However, there was a significant correlation between the degrees of hemispheric synchronization and the ability to keep still during 12-minute MEG recording periods. Our results also suggested that asynchrony in the bilateral brain auditory processing system is associated with ADHD-like symptoms in children with ASD. PMID- 27551668 TI - Cortical and subcortical brain alterations in Juvenile Absence Epilepsy. AB - Despite the common assumption that genetic generalized epilepsies are characterized by a macroscopically normal brain on magnetic resonance imaging, subtle structural brain alterations have been detected by advanced neuroimaging techniques in Childhood Absence Epilepsy syndrome. We applied quantitative structural MRI analysis to a group of adolescents and adults with Juvenile Absence Epilepsy (JAE) in order to investigate micro-structural brain changes using different brain measures. We examined grey matter volumes, cortical thickness, surface areas, and subcortical volumes in 24 patients with JAE compared to 24 healthy controls; whole-brain voxel-based morphometry (VBM) and Freesurfer analyses were used. When compared to healthy controls, patients revealed both grey matter volume and surface area reduction in bilateral frontal regions, anterior cingulate, and right mesial-temporal lobe. Correlation analysis with disease duration showed that longer disease was correlated with reduced surface area in right pre- and post-central gyrus. A possible effect of valproate treatment on brain structures was excluded. Our results indicate that subtle structural brain changes are detectable in JAE and are mainly located in anterior nodes of regions known to be crucial for awareness, attention and memory. PMID- 27551670 TI - How Microelectrode Array-Based Chick Forebrain Neuron Biosensors Respond to Glutamate NMDA Receptor Antagonist AP5 and GABAA Receptor Antagonist Musimol. AB - We have established a long-term, stable primary chick forebrain neuron (FBN) culture on a microelectrode array platform as a biosensor system for neurotoxicant screening and for neuroelectrophysiological studies for multiple purposes. This paper reports some of our results, which characterize the biosensor pharmacologically. Dose-response experiments were conducted using NMDA receptor antagonist AP5 and GABAA receptor agonist musimol (MUS). The chick FBN biosensor (C-FBN-biosensor) responds to the two agents in a pattern similar to that of rodent counterparts; the estimated EC50s (the effective concentration that causes 50% inhibition of the maximal effect) are 2.3 MUM and 0.25 MUM, respectively. Intercultural and intracultural reproducibility and long-term reusability of the C-FBN-biosensor are addressed and discussed. A phenomenon of sensitization of the biosensor that accompanies intracultural reproducibility in paired dose-response experiments for the same agent (AP5 or MUS) is reported. The potential application of the C-FBN-biosensor as an alternative to rodent biosensors in shared sensing domains (NMDA receptor and GABAA receptor) is suggested. PMID- 27551669 TI - Accuracy of automated classification of major depressive disorder as a function of symptom severity. AB - BACKGROUND: Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD). As symptom severity may influence brain activity, we investigated whether the severity of MDD affected the accuracies of machine learned MDD-vs-Control diagnostic classifiers. METHODS: Forty-five medication-free patients with DSM-IV defined MDD and 19 healthy controls participated in the study. Based on depression severity as determined by the Hamilton Rating Scale for Depression (HRSD), MDD patients were sorted into three groups: mild to moderate depression (HRSD 14-19), severe depression (HRSD 20-23), and very severe depression (HRSD >= 24). We collected functional magnetic resonance imaging (fMRI) data during both resting-state and an emotional-face matching task. Patients in each of the three severity groups were compared against controls in separate analyses, using either the resting-state or task-based fMRI data. We use each of these six datasets with linear support vector machine (SVM) binary classifiers for identifying individuals as patients or controls. RESULTS: The resting-state fMRI data showed statistically significant classification accuracy only for the very severe depression group (accuracy 66%, p = 0.012 corrected), while mild to moderate (accuracy 58%, p = 1.0 corrected) and severe depression (accuracy 52%, p = 1.0 corrected) were only at chance. With task-based fMRI data, the automated classifier performed at chance in all three severity groups. CONCLUSIONS: Binary linear SVM classifiers achieved significant classification of very severe depression with resting-state fMRI, but the contribution of brain measurements may have limited potential in differentiating patients with less severe depression from healthy controls. PMID- 27551671 TI - Flexible analysis of digital PCR experiments using generalized linear mixed models. AB - The use of digital PCR for quantification of nucleic acids is rapidly growing. A major drawback remains the lack of flexible data analysis tools. Published analysis approaches are either tailored to specific problem settings or fail to take into account sources of variability. We propose the generalized linear mixed models framework as a flexible tool for analyzing a wide range of experiments. We also introduce a method for estimating reference gene stability to improve accuracy and precision of copy number and relative expression estimates. We demonstrate the usefulness of the methodology on a complex experimental setup. PMID- 27551672 TI - Methods for comparing multiple digital PCR experiments. AB - The estimated mean copy per partition (lambda) is the essential information from a digital PCR (dPCR) experiment because lambda can be used to calculate the target concentration in a sample. However, little information is available how to statistically compare dPCR runs of multiple runs or reduplicates. The comparison of lambda values from several runs is a multiple comparison problem, which can be solved using the binary structure of dPCR data. We propose and evaluate two novel methods based on Generalized Linear Models (GLM) and Multiple Ratio Tests (MRT) for comparison of digital PCR experiments. We enriched our MRT framework with computation of simultaneous confidence intervals suitable for comparing multiple dPCR runs. The evaluation of both statistical methods support that MRT is faster and more robust for dPCR experiments performed in large scale. Our theoretical results were confirmed by the analysis of dPCR measurements of dilution series. Both methods were implemented in the dpcR package (v. 0.2) for the open source R statistical computing environment. PMID- 27551673 TI - Dual Anti-Metastatic and Anti-Proliferative Activity Assessment of Two Probiotics on HeLa and HT-29 Cell Lines. AB - OBJECTIVE: Lactobacilli are a group of probiotics with beneficial effects on prevention of cancer. However, there is scant data in relation with the impacts of probiotics in late-stage cancer progration, especially metastasis. The present original work was aimed to evaluate the anti-metastatic and anti-proliferative activity of lactobacillus rhamnosus supernatant (LRS) and lactobacillus crispatus supernatant (LCS) on the human cervical and colon adenocarcinoma cell lines (HeLa and HT-29, respectively). MATERIALS AND METHODS: In this experimental study, the anti-proliferative activities of LRS and LCS were determined through MTT assay. MRC-5 was used as a normal cell line. Expression analysis of CASP3, MMP2, MMP9, TIMP1 and TIMP2 genes was performed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), following the cell synchronization. RESULTS: Supernatants of these two lactobacilli had cytotoxic effect on HeLa, however LRS treatment was only effective on HT-29 cell line. In addition, LRS had no side effect on normal cells. It was shown that CASP3 gene expression has been reduced after treatment with supernatants of two studied lactobacilli. According to our study, LRS and LCS are efficacious in the prevention of metastasis potency in HeLa cells with decreased expression of MMP2, MMP9 and increased expression of their inhibitors. In the case of HT-29 cells, only LRS showed this effect. CONCLUSION: Herein, we have demonstrated two probiotics which have anti metastatic effects on malignant cells and they can be administrated to postpone late-stage of cancer disease. LRS and LCS are effective on HeLa cell lines while only the effect of LRS is significant on HT-29, through cytotoxic and anti metastatic mechanisms. Further assessments are required to evaluate our results on the other cancer cell lines, in advance to use these probiotics in other extensive trial studies. PMID- 27551675 TI - Epidemiological Data Management during an Outbreak of Ebola Virus Disease: Key Issues and Observations from Sierra Leone. AB - Sierra Leone experienced intense transmission of Ebola virus disease (EVD) from May 2014 to November 2015 during which a total of 8,704 confirmed cases and over 3,589 confirmed deaths were reported. Our field observation showed many issues in the EVD data management system, which may have contributed to the magnitude and long duration of the outbreak. In this perspective article, we explain the key issues with EVD data management in the field, and the resulting obstacles in analyzing key epidemiological indicators during the outbreak response work. Our observation showed that, during the latter part of the EVD outbreak, surveillance and data management improved at all levels in the country as compared to the earlier stage. We identified incomplete filling and late arrival of the case investigation forms at data management centers, difficulties in detecting double entries and merging identified double entries in the database, and lack of clear process of how death of confirmed cases in holding, treatment, and community care centers are reported to the data centers as some of challenges to effective data management. Furthermore, there was no consolidated database that captured and linked all data sources in a structured way. We propose development of a new application tool easily adaptable to new occurrences, regular data harmonization meetings between national and district data management teams, and establishment of a data quality audit system to assure good quality data as ways to improve EVD data management during future outbreaks. PMID- 27551674 TI - The Effect of An Angiogenic Cytokine on Orthodontically Induced Inflammatory Root Resorption. AB - OBJECTIVE: Orthodontically induced inflammatory root resorption (OIIRR) is an undesirable sequel of tooth movement after sterile necrosis that takes place in periodontal ligament due to blockage of blood vessels following exertion of orthodontic force. This study sought to assess the effect of an angiogenic cytokine on OIIRR in rat model. MATERIALS AND METHODS: In this experimental animal study, 50 rats were randomly divided into 5 groups of 10 each: E10, E100 and E1000 receiving an injection of 10, 100 and 1000 ng of basic fibroblast growth factor (bFGF), respectively, positive control group (CP) receiving an orthodontic appliance and injection of phosphate buffered saline (PBS) and the negative control group (CN) receiving only the anesthetic agent. A nickel titanium coil spring was placed between the first molar and the incisor on the right side of maxilla. Twenty-one days later, the rats were sacrificed. Histopathological sections were made to assess the number and area of resorption lacunae, number of blood vessels, osteoclasts and Howship's lacunae. Data were statistically analyzed using ANOVA and Tukey's honest significant difference (HSD) test. RESULTS: Number of resorption lacunae and area of resorption lacunae in E1000 (0.97 +/- 0.80 and 1. 27 +/- 0.01*10(-3), respectively) were significantly lower than in CP (4.17 +/- 0.90 and 2.77 +/- 0.01*10-3, respectively, P=0.000). Number of blood vessels, osteoclasts and Howship's lacunae were significantly higher in E1000 compared to CP (P<0.05). CONCLUSION: Tooth movement as the outcome of bone remodeling is concomitant with the formation of sterile necrosis in the periodontal ligament following blocked blood supply. Thus, bFGF can significantly decrease the risk of root resorption by providing more oxygen and angiogenesis. PMID- 27551676 TI - Refinement of the Diatom Episome Maintenance Sequence and Improvement of Conjugation-Based DNA Delivery Methods. AB - Conjugation of episomal plasmids from bacteria to diatoms advances diatom genetic manipulation by simplifying transgene delivery and providing a stable and consistent gene expression platform. To reach its full potential, this nascent technology requires new optimized expression vectors and a deeper understanding of episome maintenance. Here, we present the development of an additional diatom vector (pPtPBR1), based on the parent plasmid pBR322, to add a plasmid maintained at medium copy number in Escherichia coli to the diatom genetic toolkit. Using this new vector, we evaluated the contribution of individual yeast DNA elements comprising the 1.4-kb tripartite CEN6-ARSH4-HIS3 sequence that enables episome maintenance in Phaeodactylum tricornutum. While various combinations of these individual elements enable efficient conjugation and high exconjugant yield in P. tricornutum, individual elements alone do not. Conjugation of episomes containing CEN6-ARSH4 and a small sequence from the low GC content 3' end of HIS3 produced the highest number of diatom exconjugant colonies, resulting in a smaller and more efficient vector design. Our findings suggest that the CEN6 and ARSH4 sequences function differently in yeast and diatoms, and that low GC content regions of greater than ~500 bp are a potential indicator of a functional diatom episome maintenance sequence. Additionally, we have developed improvements to the conjugation protocol including a high-throughput option utilizing 12-well plates and plating methods that improve exconjugant yield and reduce time and materials required for the conjugation protocol. The data presented offer additional information regarding the mechanism by which the yeast-derived sequence enables diatom episome maintenance and demonstrate options for flexible vector design. PMID- 27551679 TI - Context Specificity of the ANS Stress Response during Two Regrouping Experiments in Goats. AB - The aim of this study was to analyze whether the activity of the autonomic nervous system (ANS) differs between two regrouping procedures in goats, which would indicate stimulus specificity of these stressors. Applying two regrouping procedures, we evaluated heart rate and heart rate variability (RMSSD, SDNN, and RMSSD/SDNN). The two regrouping procedures were (1) introduction of individual goats into established groups ("introduction experiment") and (2) temporary separation and subsequent reintegration of individuals from/into their group with two levels of contact during separation ("separation experiment"). In the "introduction experiment," the heart rate of introduced goats while lying decreased continuously from an average 78 to 68 beats/min from before the introduction to the last day of the introduction period. Inversely, RMSSD increased continuously from 41 to 62 ms, which, on its own, would indicate an adaptation to the situation. During the "separation experiment," heart rate while lying was higher when goats were separated in the "acoustic contact treatment" (82 beats/min on average) compared with the "restricted physical contact treatment" (75 beats/min on average). This difference reflected a higher level of arousal during the "acoustic contact treatment." However, heart rate activity did not allow detecting effects of separation or reintegration. Even though it can be assumed that both the separation and introduction of goats are stressful for goats, the ANS reactions observed in this study differed between the two management procedures indicating that the ANS activation was specific to each situation. In addition, we discuss the ANS results in context with earlier findings of variables of the hypothalamic pituitary adrenal (HPA) axis (fecal cortisol metabolites) and behavior (lying and feeding). As correspondence between ANS, HPA, and behavioral reactions was limited both within and across experiments, the results of this study underline the concept that stress response patterns are context specific. PMID- 27551677 TI - Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair. AB - Oligodendrocytes are the myelinating glia of the central nervous system. Myelination of axons allows rapid saltatory conduction of nerve impulses and contributes to axonal integrity. Devastating neurological deficits caused by demyelinating diseases, such as multiple sclerosis, illustrate well the importance of the process. In this review, we focus on the positive and negative interactions between oligodendrocytes, astrocytes, and microglia during developmental myelination and remyelination. Even though many lines of evidence support a crucial role for glia crosstalk during these processes, the nature of such interactions is often neglected when designing therapeutics for repair of demyelinated lesions. Understanding the cellular and molecular mechanisms underlying glial cell communication and how they influence oligodendrocyte differentiation and myelination is fundamental to uncover novel therapeutic strategies for myelin repair. PMID- 27551678 TI - Considerations For Optimizing Microbiome Analysis Using a Marker Gene. AB - Next-generation sequencing technologies have found a widespread use in the study of host-microbe interactions due to the increase in their throughput and their ever-decreasing costs. The analysis of human-associated microbial communities using a marker gene, particularly the 16S rRNA, has been greatly benefited from these technologies - the human gut microbiome research being a remarkable example of such analysis that has greatly expanded our understanding of microbe-mediated human health and disease, metabolism, and food absorption. 16S studies go through a series of in vitro and in silico steps that can greatly influence their outcomes. However, the lack of a standardized workflow has led to uncertainties regarding the transparency and reproducibility of gut microbiome studies. We, here, discuss the most common challenges in the archetypical 16S rRNA workflow, including the extraction of total DNA, its use as template in PCR with primers that amplify specific hypervariable regions of the gene, amplicon sequencing, the denoising and removal of low-quality reads, the detection and removal of chimeric sequences, the clustering of high-quality sequences into operational taxonomic units, and their taxonomic classification. We recommend the essential technical information that should be conveyed in publications for reproducibility of results and encourage non-experts to include procedures and available tools that mitigate most of the problems encountered in microbiome analysis. PMID- 27551680 TI - Whole-exome sequencing of a patient with severe and complex hemostatic abnormalities reveals a possible contributing frameshift mutation in C3AR1. AB - The increasing availability of genome-wide analysis has made it possible to rapidly sequence the exome of patients with undiagnosed or unresolved medical conditions. Here, we present the case of a 64-yr-old male patient with schistocytes in the peripheral blood smear and a complex and life-threatening coagulation disorder causing recurrent venous thromboembolic events, severe thrombocytopenia, and subdural hematomas. Whole-exome sequencing revealed a frameshift mutation (C3AR1 c.355-356dup, p.Asp119Alafs*19) resulting in a premature stop codon in C3AR1 (Complement Component 3a Receptor 1). Based on this finding, atypical hemolytic uremic syndrome was suspected because of a genetic predisposition, and a targeted treatment regime with eculizumab was initiated. Life-threatening hemostatic abnormalities would most likely have persisted had it not been for the implementation of whole-exome sequencing in this particular clinical setting. PMID- 27551681 TI - Exome sequencing results in successful diagnosis and treatment of a severe congenital anemia. AB - Whole-exome sequencing is increasingly used for diagnosis and identification of appropriate therapies in patients. Here, we present the case of a 3-yr-old male with a lifelong and severe transfusion-dependent anemia of unclear etiology, despite an extensive clinical workup. Given the difficulty of making the diagnosis and the potential side effects from performing interventions in patients with a congenital anemia of unknown etiology, we opted to perform whole exome sequencing on the patient and his parents. This resulted in the identification of homozygous loss-of-function mutations in the EPB41 gene, encoding erythrocyte protein band 4.1, which therefore causes a rare and severe form of hereditary elliptocytosis in the patient. Based on prior clinical experience in similar patients, a surgical splenectomy was performed that resulted in subsequent transfusion independence in the patient. This case illustrates how whole-exome sequencing can lead to accurate diagnoses (and exclusion of diagnoses where interventions, such as splenectomy, would be contraindicated), thereby resulting in appropriate and successful therapeutic intervention-a major goal of precision medicine. PMID- 27551682 TI - Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator beta-glucan in a two-case ex vivo non-small cell lung cancer study. AB - Cancer and stromal cell metabolism is important for understanding tumor development, which highly depends on the tumor microenvironment (TME). Cell or animal models cannot recapitulate the human TME. We have developed an ex vivo paired cancerous (CA) and noncancerous (NC) human lung tissue approach to explore cancer and stromal cell metabolism in the native human TME. This approach enabled full control of experimental parameters and acquisition of individual patient's target tissue response to therapeutic agents while eliminating interferences from genetic and physiological variations. In this two-case study of non-small-cell lung cancer, we performed stable isotope-resolved metabolomic (SIRM) experiments on paired CA and NC lung tissues treated with a macrophage activator beta-glucan and (13)C6-glucose, followed by ion chromatography-Fourier transform mass spectrometry (IC-FTMS) and nuclear magnetic resonance (NMR) analyses of (13)C labeling patterns of metabolites. We demonstrated that CA lung tissue slices were metabolically more active than their NC counterparts, which recapitulated the metabolic reprogramming in CA lung tissues observed in vivo. We showed beta glucan-enhanced glycolysis, Krebs cycle, pentose phosphate pathway, antioxidant production, and itaconate buildup in patient UK021 with chronic obstructive pulmonary disease (COPD) and an abundance of tumor-associated macrophages (TAMs) but not in UK049 with no COPD and much less macrophage infiltration. This metabolic response of UK021 tissues was accompanied by reduced mitotic index, increased necrosis, and enhaced inducible nitric oxide synthase (iNOS) expression. We surmise that the reprogrammed networks could reflect beta-glucan M1 polarization of human macrophages. This case study presents a unique opportunity for investigating metabolic responses of human macrophages to immune modulators in their native microenvironment on an individual patient basis. PMID- 27551683 TI - A novel FGD1 mutation in a family with Aarskog-Scott syndrome and predominant features of congenital joint contractures. AB - Mutations in FGD1 cause Aarskog-Scott syndrome (AAS), an X-linked condition characterized by abnormal facial, skeletal, and genital development due to abnormal embryonic morphogenesis and skeletal formation. Here we report a novel FGD1 mutation in a family with atypical features of AAS, specifically bilateral upper and lower limb congenital joint contractures and cardiac abnormalities. The male proband and his affected maternal uncle are hemizygous for the novel FGD1 mutation p.Arg921X. This variant is the most carboxy-terminal FGD1 mutation identified in a family with AAS and is predicted to truncate the FGD1 protein at the second to last amino acid of the carboxy-terminal pleckstrin homology (PH) domain. Our study emphasizes the importance of the 3' peptide sequence in the structure and/or function of the FGD1 protein and further demonstrates the need to screen patients with X-linked congenital joint contractures for FGD1 mutations. PMID- 27551684 TI - Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease. AB - Mutations in nuclear genes required for the replication and maintenance of mitochondrial DNA cause progressive multisystemic neuromuscular disorders with overlapping phenotypes. Biallelic mutations in C10orf2, encoding the Twinkle mitochondrial DNA helicase, lead to infantile-onset cerebellar ataxia (IOSCA), as well as milder and more severe phenotypes. We present a 13-year-old girl with ataxia, severe hearing loss, optic atrophy, peripheral neuropathy, and hypergonadotropic hypogonadism. Whole-exome sequencing revealed that the patient is compound heterozygous for previously unreported variants in the C10orf2 gene: a paternally inherited frameshift variant (c.333delT; p.L112Sfs*3) and a maternally inherited missense variant (c.904C>T; p.R302W). The identification of novel C10orf2 mutations extends the spectrum of mutations in the Twinkle helicase causing recessive disease, in particular the intermediate IOSCA phenotype. Structural modeling suggests that the p.R302W mutation and many other recessively inherited Twinkle mutations impact the position or interactions of the linker region, which is critical for the oligomeric ring structure and activity of the helicase. This study emphasizes the utility of whole-exome sequencing for the genetic diagnosis of a complex multisystemic disorder. PMID- 27551685 TI - Structural analysis of a signal peptide inside the ribosome tunnel by DNP MAS NMR. AB - Proteins are synthesized in cells by ribosomes and, in parallel, prepared for folding or targeting. While ribosomal protein synthesis is progressing, the nascent chain exposes amino-terminal signal sequences or transmembrane domains that mediate interactions with specific interaction partners, such as the signal recognition particle (SRP), the SecA-adenosine triphosphatase, or the trigger factor. These binding events can set the course for folding in the cytoplasm and translocation across or insertion into membranes. A distinction of the respective pathways depends largely on the hydrophobicity of the recognition sequence. Hydrophobic transmembrane domains stabilize SRP binding, whereas less hydrophobic signal sequences, typical for periplasmic and outer membrane proteins, stimulate SecA binding and disfavor SRP interactions. In this context, the formation of helical structures of signal peptides within the ribosome was considered to be an important factor. We applied dynamic nuclear polarization magic-angle spinning nuclear magnetic resonance to investigate the conformational states of the disulfide oxidoreductase A (DsbA) signal peptide stalled within the exit tunnel of the ribosome. Our results suggest that the nascent chain comprising the DsbA signal sequence adopts an extended structure in the ribosome with only minor populations of helical structure. PMID- 27551686 TI - An exciton-polariton laser based on biologically produced fluorescent protein. AB - Under adequate conditions, cavity polaritons form a macroscopic coherent quantum state, known as polariton condensate. Compared to Wannier-Mott excitons in inorganic semiconductors, the localized Frenkel excitons in organic emitter materials show weaker interaction with each other but stronger coupling to light, which recently enabled the first realization of a polariton condensate at room temperature. However, this required ultrafast optical pumping, which limits the applications of organic polariton condensates. We demonstrate room temperature polariton condensates of cavity polaritons in simple laminated microcavities filled with biologically produced enhanced green fluorescent protein (eGFP). The unique molecular structure of eGFP prevents exciton annihilation even at high excitation densities, thus facilitating polariton condensation under conventional nanosecond pumping. Condensation is clearly evidenced by a distinct threshold, an interaction-induced blueshift of the condensate, long-range coherence, and the presence of a second threshold at higher excitation density that is associated with the onset of photon lasing. PMID- 27551687 TI - Visualizing weakly bound surface Fermi arcs and their correspondence to bulk Weyl fermions. AB - Fermi arcs are the surface manifestation of the topological nature of Weyl semimetals, enforced by the bulk-boundary correspondence with the bulk Weyl nodes. The surface of tantalum arsenide, similar to that of other members of the Weyl semimetal class, hosts nontopological bands that obscure the exploration of this correspondence. We use the spatial structure of the Fermi arc wave function, probed by scanning tunneling microscopy, as a spectroscopic tool to distinguish and characterize the surface Fermi arc bands. We find that, as opposed to nontopological states, the Fermi arc wave function is weakly affected by the surface potential: it spreads rather uniformly within the unit cell and penetrates deeper into the bulk. Fermi arcs reside predominantly on tantalum sites, from which the topological bulk bands are derived. Furthermore, we identify a correspondence between the Fermi arc dispersion and the energy and momentum of the bulk Weyl nodes that classify this material as topological. We obtain these results by introducing an analysis based on the role the Bloch wave function has in shaping quantum electronic interference patterns. It thus carries broader applicability to the study of other electronic systems and other physical processes. PMID- 27551689 TI - Can mantle convection be self-regulated? AB - The notion of self-regulating mantle convection, in which heat loss from the surface is constantly adjusted to follow internal radiogenic heat production, has been popular for the past six decades since Urey first advocated the idea. Thanks to its intuitive appeal, this notion has pervaded the solid earth sciences in various forms, but approach to a self-regulating state critically depends on the relation between the thermal adjustment rate and mantle temperature. I show that, if the effect of mantle melting on viscosity is taken into account, the adjustment rate cannot be sufficiently high to achieve self-regulation, regardless of the style of mantle convection. The evolution of terrestrial planets is thus likely to be far from thermal equilibrium and be sensitive to the peculiarities of their formation histories. Chance factors in planetary formation are suggested to become more important for the evolution of planets that are more massive than Earth. PMID- 27551688 TI - Self-organization in precipitation reactions far from the equilibrium. AB - Far from the thermodynamic equilibrium, many precipitation reactions create complex product structures with fascinating features caused by their unusual origins. Unlike the dissipative patterns in other self-organizing reactions, these features can be permanent, suggesting potential applications in materials science and engineering. We review four distinct classes of precipitation reactions, describe similarities and differences, and discuss related challenges for theoretical studies. These classes are hollow micro- and macrotubes in chemical gardens, polycrystalline silica carbonate aggregates (biomorphs), Liesegang bands, and propagating precipitation-dissolution fronts. In many cases, these systems show intricate structural hierarchies that span from the nanometer scale into the macroscopic world. We summarize recent experimental progress that often involves growth under tightly regulated conditions by means of wet stamping, holographic heating, and controlled electric, magnetic, or pH perturbations. In this research field, progress requires mechanistic insights that cannot be derived from experiments alone. We discuss how mesoscopic aspects of the product structures can be modeled by reaction-transport equations and suggest important targets for future studies that should also include materials features at the nanoscale. PMID- 27551690 TI - Physical Activity Levels in a Community Lifestyle Intervention: A Randomized Trial. AB - BACKGROUND: A behavioral lifestyle intervention program with goals of increasing physical activity (PA) and losing weight was shown to be efficacious for preventing type 2 diabetes and decreasing risk for cardiovascular disease in the U.S. Diabetes Prevention Program (DPP). Modified versions of the DPP lifestyle intervention are being translated into diverse community settings and have been successful in decreasing weight and improving metabolic markers. However, comprehensive evaluations of PA levels within these community translation intervention efforts are rare. PURPOSE: To evaluate the effectiveness of a DPP based community lifestyle intervention for improving PA levels. METHODS: 223 overweight adults at-risk for type 2 diabetes and/or cardiovascular disease were randomized (immediate or 6-month delayed-start) to a 12-month DPP-based lifestyle intervention. Past-month PA level was assessed at baseline and post-intervention with the Modifiable Activity Questionnaire. Simple and mixed-effects regression models were used to determine changes in PA level between and within groups over time. RESULTS: The between-group mean difference for change in PA levels from baseline to 6 months indicated significantly greater improvement in the intervention compared to the delayed-start group [+6.72 (SE=3.01) MET-hrs/week; p=0.03]. Examining combined within-group change from baseline to post intervention, mean PA levels significantly increased by +14.69 (SE=1.43) and +9.50 (SE= 1.40) MET-hrs/week at 6 and 12 months post-intervention, respectively. This PA change offset to approximately +10 MET-hrs/week at both 6 and 12 months after adjusting for baseline PA level and season (all; p<0.01). Other than season, sex impacted on change in PA level. CONCLUSIONS: This community-based lifestyle intervention significantly increased PA levels among overweight adults at risk for type 2 diabetes and cardiovascular disease, even after adjusting for key variables. CLINICALTRIALSGOV IDENTIFIER: NCT01050205. PMID- 27551691 TI - Adolescents with and without idiopathic scoliosis have similar self-reported level of physical activity: a cross-sectional study. AB - BACKGROUND: Little is known about physical activity levels in individuals with idiopathic scoliosis. The aim of this study was to describe the level of physical activity in adolescents with and without idiopathic scoliosis. METHODS: Two hundred thirty-nine adolescents, median (25th, 75th percentile) age 16.0 (14.4, 17.6) with idiopathic scoliosis and 58 randomly recruited population-based individuals without scoliosis aged 14.6 (12.8, 16.3) participated. The 239 idiopathic scoliosis patients consisted of 88 untreated, 43 previously braced, 36 with ongoing brace-treatment and 72 surgically treated individuals. Main outcome measure was the proportion achieving at least moderate activity level, as estimated by the International Physical Activity Questionnaire short form (IPAQ SF). Other outcome measures were Metabolic Equivalent Task (MET) minutes/week, time spent sitting, spare time activity level and sporting activities. Statistical analyses were adjusted for age and sex. RESULTS: The proportion of individuals with scoliosis with moderate activity level was 180 out of 239 (75 %) and for individuals without scoliosis 49 out of 58 (85 %) (p = 0.14). Median MET minutes/week (25th,75th percentile) was for individuals with scoliosis scoliosis 1977 (840,3777) and for individuals without scoliosis 2120 (887,4598) (p = 0.11). Sporting activities did not differ (p = 0.28). The ongoing brace-treatment group had a significantly higher proportion of individuals categorizing themselves at high spare time activity level compared to the surgically treated and previously braced individuals (p = 0.046). No difference was seen between the treatment groups regarding the proportion achieving moderate activity (p = 0.11) and sporting activities (p = 0.20). Median MET minutes/week was 2160 (794,3797) for the untreated group, 989 (661,2706) for the previously braced group, 2055 (1010, 4026) for the surgery group and 2106 (990,4480) for the ongoing brace-treatment group (p = 0.031). CONCLUSION: Adolescents with idiopathic scoliosis show similar levels of self-reported physical activity as individuals without idiopathic scoliosis. Bracing and surgery do not appear to inhibit physical activity. PMID- 27551692 TI - Fifteen to twenty-five year functional outcomes of twenty-two patients treated with posterior Cotrel-Dubousset type instrumentation: a limited but detailed review of outcomes. AB - BACKGROUND: Long-term outcomes of patients undergoing extensive fusions for adolescent idiopathic scoliosis (AIS) have conflicting results. Moskowitz found uninstrumented scoliosis fusion patients had similar back pain as a normal age matched population. Recently, long-term outcomes of patients with Harrington rod instrumentation were reviewed and found similar functional outcome scores to non scoliosis patients, with trending toward worse outcomes when fusions extended to L4. Our study examined long-term functional outcomes of patients treated with Cotrel-Dubousset (CD) instrumentation and determined whether distal level of instrumented fusion (L4 and L5) correlate with increased back pain or lower functional level. METHODS: Retrospective review of AIS surgeries from 1986 to 1996 was undertaken. Patient demographics and surgical data were collected via case-note audit. Patients were contacted and asked to complete a series of functional outcome questionnaires including visual analog scales (VAS) for pain, Short-Form 36 (SF-36), Scoliosis Research Society 22 (SRS-22) and Oswestry Disability Index (ODI) for function. ANOVA technique categorically compared outcome scores to most distal levels of fusion. Linear regression compared patient reported outcomes to time elapsed since surgery. Statistical significance was p < 0.05. RESULTS: One hundred twelve patients were identified, 50 patients were contacted, and 22 agreed to participation and completed a full assessment. Follow-up time since surgery ranged from 15 to 26 years and age ranged from 30 to 43 years. Six patients reported daily VAS back pain of >=5; with a mean of 2.5. Back pain was not associated with level of distal fusion (p = 0.92). ODI was 15.36, with six patients' ODI >20. No relationship was shown between ODI and distal level of fusion (p = 0.72). SF-36 and SRS 22 values were also not related to distal level of instrumentation. Patient reported VAS back pain scores (r(2) = 0.18, p = 0.05), ODI (r(2) = 0.09, p = 0.17), and SF-36 and SRS-22 were not worse in patients with longer follow-up over time. Back pain and certain functional score subcategories of the SF-36 and SRS-22 trended toward improved results over time. CONCLUSIONS: Most patients who underwent multi-segment spinal fixation appeared to do well long-term, with minimal back pain. Lowest instrumented segment did not appear to be associated with increased back pain after 15 to 25 years follow-up. PMID- 27551693 TI - Spin wave localization in tangentially magnetized films. AB - We present an analytical description of localized spin wave modes that form in a parabolic field minimum in a thin ferromagnetic film. Mode profiles proportional to Hermite functions are eigenfuctions of the applied field and exchange parts of the equations of motion, and also provide a basis for numerical approximation of magnetostatic interactions. We find that the spin wave modes are roughly equally spaced in frequency and have roughly equal coupling to a uniform driving field. The calculated mode frequencies and corresponding profiles of localized spin wave modes are in good agreement with micromagnetic modeling and previously published experimental results on multiple resonances from a series of localized modes detected by ferromagnetic resonance force microscopy. PMID- 27551694 TI - Cushing's syndrome. PMID- 27551695 TI - The Lancet in 19th-century America. PMID- 27551696 TI - Irving Gottesman. PMID- 27551697 TI - Introduction. PMID- 27551698 TI - Antibodies in the Treatment of Psoriasis: IL-12/23 p40 and IL-17a. AB - The anti-tumor necrosis factor (TNF)-alpha agents represent the second generation of psoriasis therapy. Research has produced a third generation of biologic treatments, some of which offer greater efficacy than the TNF-alpha inhibitors. This article reviews the data documenting the efficacy and safety of three types of biologics. PMID- 27551699 TI - Mole's Wow! So now you have your own lab! Part IV--The big fight. By Caveman. PMID- 27551700 TI - [Not Available]. PMID- 27551701 TI - [Tribute to Jean-Louis Davin (1953-2016)]. PMID- 27551702 TI - AUTHORS' RESPONSE. PMID- 27551703 TI - Assessing Medical Student Knowledge of Imaging Modality Selection Before and After a General Radiology Elective: A Comparison of MS-IIs, MS-IIIs, and MS-IVs. AB - RATIONALE AND OBJECTIVES: Correct selection of imaging tests is essential f or clinicians but until recently has been largely neglected in medical education. How and when students acquire such non-interpretive skills are unknown. This study will assess student knowledge of imaging test selection before and after a general radiology elective. MATERIALS AND METHODS: Between 2008 and 2015, an unannounced 13-item test was administered to second, third, and fourth-year students on the first and last days of the Johns Hopkins School of Medicine radiology elective. Scores (0-13) were based on the American College of Radiology Appropriateness Criteria. Pre- and posttest means were compared using paired samples t tests. Whether performance on the pretest and posttest differed by class year was assessed using analysis of variance and Kruskal-Wallis, respectively, and whether year was associated with posttest score after controlling for pretest score was assessed using analysis of covariance. RESULTS: Posttest means were significantly higher than pretest means for students in all years (P values <.0001). Pretest scores differed by year (F(2, 360) = 66.85, P <.0001): fourth-year students scored highest (mean = 9.96 of 13) and second-year students scored lowest (mean = 7.01 of 13). Posttest scores did not differ (chi2(2, 270) = 0.348, P = .841). Year in school had no independent effect on posttest score (F(2, 239) = 0.45, P = .637). CONCLUSION: Knowledge of modality selection increases with clinical training, but room for improvement remains. A general radiology elective increases this knowledge. Second-year students improve most, suggesting that taking radiology early is efficient, but further research to evaluate retention of this knowledge is needed. Medical student education in radiology must increasingly recognize and address non-interpretive skills and intelligent imaging utilization. PMID- 27551704 TI - Usefulness of Quality Measures Questioned, May Be Misleading. PMID- 27551705 TI - Study Finds Only 1 in 21 Quality Measures Valid. PMID- 27551706 TI - Self-Reported Data May Be Inaccurate. PMID- 27551707 TI - TJC Allows Docs to Text Orders, Still Use Caution. PMID- 27551708 TI - TJC Launches New SAFER Scoring Matrix. PMID- 27551709 TI - Work abroad: Visa to visit. PMID- 27551710 TI - [Alon P. Winnie: Inspiring modern regional anaesthesia]. PMID- 27551711 TI - NOTE FROM THE EDITOR. PMID- 27551712 TI - Threat from Emerging Vectorborne Viruses. PMID- 27551714 TI - Etymologia: Orthobunyavirus [or"tho-bun'ye-vi"res]. PMID- 27551713 TI - Inspiration and Insecticide from the Flower Garden. PMID- 27551715 TI - Is MDx cost-effective for infectious disease applications? PMID- 27551716 TI - Measles Virus Matrix Protein Inhibits Host Cell Transcription. AB - Measles virus (MeV) is a highly contagious virus that still causes annual epidemics in developing countries despite the availability of a safe and effective vaccine. Additionally, importation from endemic countries causes frequent outbreaks in countries where it has been eliminated. The M protein of MeV plays a key role in virus assembly and cytopathogenesis; interestingly, M is localised in nucleus, cytoplasm and membranes of infected cells. We have used transient expression of M in transfected cells and in-cell transcription assays to show that only some MeV M localizes to the nucleus, in addition to cell membranes and the cytoplasm as previously described, and can inhibit cellular transcription via binding to nuclear factors. Additionally, MeV M was able to inhibit in vitro transcription in a dose-dependent manner. Importantly, a proportion of M is also localized to nucleus of MeV infected cells at early times in infection, correlating with inhibition of cellular transcription. Our data show, for the first time, that MeV M may play a role early in infection by inhibiting host cell transcription. PMID- 27551717 TI - A Molecular Probe for the Detection of Polar Lipids in Live Cells. AB - Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1TM to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1TM interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1TM it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1TM was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1TM detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1TM. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1TM staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1TM is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular compartments. PMID- 27551718 TI - Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats. AB - Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury. PMID- 27551719 TI - Rich and Poor Cities in Europe. An Urban Scaling Approach to Mapping the European Economic Transition. AB - Recent advances in the urban science make broad use of the notion of scaling. We focus here on the important scaling relationship between the gross metropolitan product (GMP) of a city and its population (pop). It has been demonstrated that GMP ? Y Ypopbeta with beta always greater than 1 and close to 1.2. This fundamental finding highlights a universal rule that holds across countries and cultures and might explain the very nature of cities. However, in an increasingly connected world, the hypothesis that the economy of a city solely depends on its population might be questionable. Using data for 248 cities in the European Union between 2005 and 2010, we found a double GMP/pop scaling regime. For West EU cities, beta = 1 over the whole the period, while for post-communist cities beta > 1 and increases from ~1.2 to ~1.4. The evolution of the scaling exponent describes the convergence of post-communist European cities to open and liberal economies. We propose a simple model of economic convergence in which, under stable political conditions, a linear GMP/pop scaling is expected for all cities. The results suggest that the GMP/pop super-linear scaling represents a phase of economic growth rather than a steady, universal urban feature. The results also suggest that relationships between cities are embedded in their political and economic context and cannot be neglected in explanations of cities, urbanization and urban economics. PMID- 27551721 TI - Correction: Type 2 Diabetes Risk Allele Loci in the Qatari Population. AB - [This corrects the article DOI: 10.1371/journal.pone.0156834.]. PMID- 27551720 TI - Chemokine Receptors, CXCR1 and CXCR2, Differentially Regulate Exosome Release in Hepatocytes. AB - Exosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury. In the current study, we sought to determine if the regulatory effects of CXCR1 and CXCR2 on liver recovery and regeneration might occur via altered release of hepatocyte exosomes. We found that hepatocyte release of exosomes was dependent upon CXCR1 and CXCR2. CXCR1 deficient hepatocytes produced fewer exosomes, whereas CXCR2-deficient hepatocytes produced more exosomes compared to their wild-type controls. In CXCR2 deficient hepatocytes, there was increased activity of neutral sphingomyelinase (Nsm) and intracellular ceramide. CXCR1-deficient hepatocytes had no alterations in Nsm activity or ceramide production. Interestingly, exosomes from CXCR1 deficient hepatocytes had no effect on hepatocyte proliferation, due to a lack of neutral ceramidase and sphingosine kinase. The data demonstrate that CXCR1 and CXCR2 regulate hepatocyte exosome release. The mechanism utilized by CXCR1 remains elusive, but CXCR2 appears to modulate Nsm activity and resultant production of ceramide to control exosome release. CXCR1 is required for packaging of enzymes into exosomes that mediate their hepatocyte proliferative effect. PMID- 27551722 TI - Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model. AB - Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P < 0.01). Compared with the LPS group, bifidobacterium significantly decreased the production of IL-6 and TNF-alpha (P < 0.01) and suppressed zonulin release (P < 0.05). In addition, bifidobacterium pretreatment up-regulated occludin, claudin-3 and ZO-1 expression (P < 0.01) and also preserved these proteins localization at TJ compared with the LPS group. In the in vivo study, bifidobacterium decreased the incidence of NEC from 88 to 47% (P < 0.05) and reduced the severity in the NEC model. Increased levels of IL-6 and TNF-alpha in the ileum of NEC rats were normalized in bifidobacterium treated rats (P < 0.05). Moreover, administration of bifidobacterium attenuated the increase in intestinal permeability (P < 0.01), decreased the levels of serum zonulin (P < 0.05), normalized the expression and localization of TJ proteins in the ileum compared with animals with NEC. We concluded that bifidobacterium may protect against intestinal barrier dysfunction both in vitro and in NEC. This protective effect is associated with inhibition of proinflammatory cytokine secretion, suppression of zonulin protein release and improvement of intestinal TJ integrity. PMID- 27551724 TI - Comparison of MALDI-TOF MS, nucleic acid hybridization and the MPT64 immunochromatographic test for the identification of M. tuberculosis and non tuberculosis Mycobacterium species. AB - Mycobacteria are an important cause of morbidity in humans. Rapid and accurate mycobacterial identification is important for improving patient outcomes. However, identification of Mycobacterium species is not easy, due to the slow and fastidious growth of mycobacteria. Recently, biochemical, sequencing, and probing methods have come to be used for identification. This study compared the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of M.tuberculosis and non tuberculosis Mycobacteria (NTM) to those of nucleic acid hybridization (NAH) and the MPT64 immunochromatographic test. A total of 69 isolates from Marmara University Hospital, Microbiology Laboratory obtained between 2012 and 2013 were included in our study. All strains were grown on Lowenstein-Jensen and Middlebrook 7H9 medium. Among the 69 isolates, 56 (81%) were isolated as Mycobacterium tuberculosis complex (MTC), and 13 (19%) were isolated as NTM by the MPT64 ICT. NAH was able to identify all isolates to the species level. The isolated NTM included M. intracellulare (n:5), M. lentiflavum (n:3), M. xenopi (n:2), M. malmoense (n:1), M. abscessus (n:1), and M. avium (n:1). MALDI-TOF MS identified 88% of the mycobacterial isolates. All M. tuberculosis strains were identified correctly, but the ratio was 38.5% for NTM. Mycobacterial identification using MALDI-TOF MS takes 45 minutes and costs 3 Euro/test, whereas mycobacterial identification using NAH takes 6-7 hours and costs 30 Euro/test. In conclusion, MALDI-TOF MS has the potential to identify mycobacteria in the clinical laboratory setting by reducing identification turnaround time and laboratory costs for isolate referral. PMID- 27551725 TI - Monotherapy with darunavir/ritonavir or lopinavir/ritonavir versus standard antiretroviral therapy: a randomized clinical trial (2pm Study). AB - In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm. Virological failure was detected in only one patient receiving LPV/r-MT. The LPV/r-MT arm showed a modest worsening in lipid profile. PMID- 27551726 TI - Increasing use and accessibility of anti parasitic drugs for migrants with neglected diseases at a time of migratory emergency. AB - This work focused on Schistosoma spp. as a potential agent of gross haematuria in non endemic areas. This change in epidemiology is mainly due to recent migratory flows. Moreover it emphasized the needfor cultural action (aimed at Urologists, Dermatologists, General Practitioners and Emergency Medicine doctors) to provide the elements for a correct and timely diagnosis. But the most important issue raised by this paper is the call for a fast track supply of drugs (usually not available in Italy) to field operators for treating tropical diseases. PMID- 27551727 TI - Diagnostic accuracy of Xpert MTB/RIF versus smear microscopy in the early diagnosis tuberculosis in the real life of "Umberto I" Hospital Rome. AB - Early diagnosis of tuberculosis (TB) is one of the primary challenges in curtailing the spread of TB. This study aimed to determine the diagnostic accuracy of Xpert MTB/RIF for the identification of M. tuberculosis in clinical specimens, and compare this to a microscopist's diagnostic performance. Xpert MTB/ RIF was positive in all specimens with culture-confirmed TB, giving a higher sensitivity than the smear microscopy (100% versus 63%). The use of the Xpert MTB/RIF, as part of routine assay, permits rapid diagnosis of TB and enables clinicians to start an effective treatment. PMID- 27551728 TI - Zika virus: issues of concern. PMID- 27551729 TI - Living Life on a Magnet. PMID- 27551723 TI - Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent. AB - BACKGROUND: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. METHODS: We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. RESULTS: In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56 0.75, p = 3.32 * 10-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 * 10-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 * 10-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 * 10-7). Single marker analyses identified 17 of the 84 BMI associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. CONCLUSIONS: BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer. PMID- 27551731 TI - Disparities in care by insurance status for individuals with rheumatoid arthritis: analysis of the medical expenditure panel survey, 2006-2009. AB - OBJECTIVE: Treatment guidelines for rheumatoid arthritis (RA) recommend early, aggressive treatment with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs) to minimize long-term disability. We aimed to assess differences in medical resource utilization, drug therapy, and health outcomes among RA patients by insurance type in the United States. METHODS: Individuals with a self-reported diagnosis of RA were identified in the Medical Expenditure Panel Survey (MEPS) database, 2006-2009. Data regarding sociodemographic characteristics, insurance type and status, and outcomes (including health care resource utilization, prescription medication use, health status, and patient reported barriers to health care) were extracted. Multivariable regression analyses were used to examine the impact of insurance type (private, Medicare, Medicaid, or uninsured) on outcome measures while controlling for age group, sex, and race/ethnicity. RESULTS: A total of 693 individuals with a self-reported diagnosis of RA during the study period were identified; 423 were aged 18-64 years and 270 were aged >=65 years. Among patients aged 18-64, those with Medicaid or who were uninsured were less likely than those with private insurance to visit a rheumatologist (adjusted odds ratio [aOR] 0.13 and 0.17, respectively; p < .001) and to receive biologic DMARDS (aOR 0.09 [p < .001] and 0.16 [p < .01], respectively); those with Medicaid were also less likely to receive nonbiologic DMARDS (aOR 0.26 [p < .01]). Those with Medicaid were more likely than those with private insurance to be unable/delayed in getting prescription drugs (aOR 2.9 [p < .05]), to experience cognitive, social, and physical limitations (aOR 8.7 [p < .001], 4.7 [p < .001], and 2.5 [p < .05], respectively); they also reported significantly lower general health and health-related quality of life. Patients aged >=65 experienced greater equity in care and outcomes. CONCLUSIONS: Younger RA patients with Medicaid (including those who receive coverage under the Medicaid expansion component of the Affordable Care Act) may be at risk for inadequate treatment. PMID- 27551730 TI - The Mutual Interactions between Mesenchymal Stem Cells and Myoblasts in an Autologous Co-Culture Model. AB - Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC in vitro in terms of the features important for the muscle regeneration process. Primary caprine muscle derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H2O2 on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders. PMID- 27551732 TI - Linker Flexibility Facilitates Module Exchange in Fungal Hybrid PKS-NRPS Engineering. AB - Polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) each give rise to a vast array of complex bioactive molecules with further complexity added by the existence of natural PKS-NRPS fusions. Rational genetic engineering for the production of natural product derivatives is desirable for the purpose of incorporating new functionalities into pre-existing molecules, or for optimization of known bioactivities. We sought to expand the range of natural product diversity by combining modules of PKS-NRPS hybrids from different hosts, hereby producing novel synthetic natural products. We succeeded in the construction of a functional cross-species chimeric PKS-NRPS expressed in Aspergillus nidulans. Module swapping of the two PKS-NRPS natural hybrids CcsA from Aspergillus clavatus involved in the biosynthesis of cytochalasin E and related Syn2 from rice plant pathogen Magnaporthe oryzae lead to production of novel hybrid products, demonstrating that the rational re-design of these fungal natural product enzymes is feasible. We also report the structure of four novel pseudo pre-cytochalasin intermediates, niduclavin and niduporthin along with the chimeric compounds niduchimaeralin A and B, all indicating that PKS-NRPS activity alone is insufficient for proper assembly of the cytochalasin core structure. Future success in the field of biocombinatorial synthesis of hybrid polyketide nonribosomal peptides relies on the understanding of the fundamental mechanisms of inter-modular polyketide chain transfer. Therefore, we expressed several PKS NRPS linker-modified variants. Intriguingly, the linker anatomy is less complex than expected, as these variants displayed great tolerance with regards to content and length, showing a hitherto unreported flexibility in PKS-NRPS hybrids, with great potential for synthetic biology-driven biocombinatorial chemistry. PMID- 27551733 TI - Diagnosis of Intraabdominal Fluid Extravasation After Hip Arthroscopy With Point of-Care Ultrasonography Can Identify Patients at an Increased Risk for Postoperative Pain. AB - BACKGROUND: Intraabdominal fluid extravasation (IAFE) after hip arthroscopy has historically been diagnosed in catastrophic circumstances with abdominal compartment syndrome requiring diuresis or surgical decompression. A previous retrospective study found the prevalence of symptomatic IAFE requiring diuresis or decompression to be 0.16%, with risk factors including surgical procedure and high pump pressures. IAFE can be diagnosed rapidly by using point-of-care ultrasound (POCUS) via the Focused Assessment With Sonography for Trauma (FAST) examination, which is a well-established means to detect free fluid with high specificity and sensitivity. In this study, we used POCUS to determine the incidence of IAFE in patients undergoing hip arthroscopy. We predicted a higher incidence and that patients with IAFE would have symptoms of peritoneal irritation such as pain and nausea. METHODS: One hundred patients undergoing ambulatory hip arthroscopy were prospectively enrolled. A FAST examination was performed after induction by a trained anesthesiologist to exclude the preoperative presence of intraperitoneal fluid. Postoperatively, the same anesthesiologist repeated the FAST examination, and patients with new fluid in the abdominal or pelvic peritoneum were diagnosed with IAFE. Patients were followed up in the postanesthesia care unit (PACU) for 6 hours assessing pain, antiemetic and opioid use, and length of stay. RESULTS: Sixteen of 100 patients were found to have IAFE (16.0%; 99% confidence interval [CI], 8.4-28.1). These patients had, on average, a greater increase in pain score from their baseline assessment throughout their entire PACU stay (adjusted difference in means [99% CI]: 2.1 points [0.4-3.9]; P = .002). Patients with IAFE used more opioids, but this difference did not meet statistical significance (adjusted difference in means [99% CI]: 7.8 mg oral morphine equivalents [-2.8 to 18.3]; P = .053). There were no differences in postoperative nausea interventions or length of stay. CONCLUSIONS: Our incidence of IAFE was 16%, showing that IAFE occurs quite commonly in hip arthroscopy. Patients with IAFE had a greater increase in pain scores from baseline throughout the PACU stay. None of our patients required interventions. These findings suggest that even a small amount of new fluid in the peritoneum may be associated with a worse postoperative experience. This study brings awareness to a common yet potentially life-threatening complication of hip arthroscopy and highlights a unique and meaningful way that anesthesiologists in the perioperative setting can use POCUS to rapidly identify and guide management of these patients. Further studies with a larger sample size are needed to identify surgical and patient risk factors. PMID- 27551734 TI - Point-of-Care Ultrasound: Novel Technology to Routine Perioperative Assessment Tool. PMID- 27551736 TI - Active Management of Labor Epidural Analgesia Is the Key to Successful Conversion of Epidural Analgesia to Cesarean Delivery Anesthesia. PMID- 27551737 TI - Smartphone Application-based Medical Devices: Twenty-first Century Data Democratization or Anarchy? PMID- 27551735 TI - Recent Insights Into Molecular Mechanisms of Propofol-Induced Developmental Neurotoxicity: Implications for the Protective Strategies. AB - Mounting evidence has demonstrated that general anesthetics could induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long-term memory and learning abnormalities. Propofol is a commonly used intravenous anesthetic agent for the induction and maintenance of anesthesia and procedural and critical care sedation in children. Compared with other anesthetic drugs, little information is available on its potential contributions to neurotoxicity. Growing evidence from multiple experimental models showed a similar neurotoxic effect of propofol as observed in other anesthetic drugs, raising serious concerns regarding pediatric propofol anesthesia. The aim of this review is to summarize the current findings of propofol-induced developmental neurotoxicity. We first present the evidence of neurotoxicity from animal models, animal cell culture, and human stem cell-derived neuron culture studies. We then discuss the mechanism of propofol-induced developmental neurotoxicity, such as increased cell death in neurons and oligodendrocytes, dysregulation of neurogenesis, abnormal dendritic development, and decreases in neurotrophic factor expression. Recent findings of complex mechanisms of propofol action, including alterations in microRNAs and mitochondrial fission, are discussed as well. An understanding of the toxic effect of propofol and the underlying mechanisms may help to develop effective novel protective or therapeutic strategies for avoiding the neurotoxicity in the developing human brain. PMID- 27551738 TI - In Response. PMID- 27551739 TI - Trends and Challenges in Clinical Monitoring: Papers From the 2015 IAMPOV Symposium. PMID- 27551740 TI - Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and Functionalization: Reaction Design and Beyond. AB - Visible-light photocatalysis has recently received increasing attention from chemists because of its wide application in organic synthesis and its significance for sustainable chemistry. This catalytic strategy enables the generation of various reactive species, frequently without stoichiometric activation reagents under mild reaction conditions. Manipulation of these reactive intermediates can result in numerous synthetically useful bond formations in a controllable manner. In this Account, we describe our recent advances in the rational design and strategic application of photocatalysis in the synthesis of various synthetically and biologically important heterocycles. Our main research efforts toward this goal can be classified into four categories: formal cycloaddition and cyclization reactions, radical-mediated olefin functionalization/cyclization cascades, photocatalytic generation and cyclization of N-centered radicals, and photocatalytic functionalization of heterocycles by visible-light-induced dual catalysis. Inspired by the wide application of tertiary amines as reductive additives in photoredox catalysis, we exploited a series of readily accessible or rationally designed tertiary amines with reactive sites in a range of photocatalytic formal cycloaddition and cyclization reactions, providing efficient access to diverse nitrogen heterocycles. Employing various photogenerated radical species, we further developed a series of radical-mediated olefin functionalization/cyclization cascade reactions to successfully assemble various five- and six-membered heterocycles. We have also achieved for the first time the direct catalytic conversion of recalcitrant N-H bonds into neutral N-centered radicals through a visible-light-photocatalytic oxidative deprotonation electron transfer. Using this generic strategy, we have devised several types of radical cyclizations of unsaturated hydrazones, leading to the construction of diversely functionalized pyrazoline and pyridazine derivatives in good yields and selectivity. Moreover, we have demonstrated that this photocatalysis can serve as a mild and highly selective tool for direct functionalization of heterocycles because of its powerful capability to controllably generate diverse reactive intermediates under mild reaction conditions. Guided by the fundamental principles of photocatalysis and the redox properties of the photocatalysts, we successfully developed an array of dual-catalyst systems by combining the photocatalysts with palladium, nickel, or amine, enabling efficient and selective coupling reactions. An intriguing phototandem catalytic system using a single photocatalyst was also identified for the development of cascade reactions. Notably, some of the newly developed methodologies have also been successfully utilized for late-stage modification of biologically active natural compounds and complex molecules and as key steps for formal synthesis of natural products. This Account presents a panoramic view and the logic of our recent contributions to the design, development, and application of photocatalytic systems and reactions that provide not only methods for the efficient synthesis of heterocycles but also useful insights into the exploration of new photochemical reactions. PMID- 27551742 TI - Extended ocular drug delivery systems for the anterior and posterior segments: biomaterial options and applications. AB - INTRODUCTION: The development of new therapies for treating various eye conditions has led to a demand for extended release delivery systems, which would lessen the need for frequent application while still achieving therapeutic drug levels in the target tissues. Areas covered: Following an overview of the different ocular drug delivery modalities, this article surveys the biomaterials used to develop sustained release drug delivery systems. Microspheres, nanospheres, liposomes, hydrogels, and composite systems are discussed in terms of their primary materials. The advantages and disadvantages of each drug delivery system are discussed for various applications. Recommendations for modifications and strategies for improvements to these basic systems are also discussed. Expert opinion: An ideal sustained release drug delivery system should be able to encapsulate and deliver the necessary drug to the target tissues at a therapeutic level without any detriment to the drug. Drug encapsulation should be as high as possible to minimize loss and unless it is specifically desired, the initial burst of drug release should be kept to a minimum. By modifying various biomaterials, it is possible to achieve sustained drug delivery to both the anterior and posterior segments of the eye. PMID- 27551741 TI - Reduction Sensitive PEG Hydrogels for Codelivery of Antigen and Adjuvant To Induce Potent CTLs. AB - Educating our immune system via vaccination is an attractive approach to combat infectious diseases. Eliciting antigen specific cytotoxic T cells (CTLs), CD8+ effector T cells, is essential in controlling intracellular infectious diseases such as influenza (Flu), tuberculosis (TB), hepatitis, and HIV/AIDS, as well as tumors. However, vaccination utilizing subunit peptides to elicit a potent CD8+ T cell response with antigenic peptides is typically ineffective due to poor immunogenicity. Here we have engineered a reduction sensitive nanoparticle (NP) based subunit vaccine for intracellular delivery of an antigenic peptide and immunostimulatory adjuvant. We have co-conjugated an antigenic peptide (ovalbumin derived CTL epitope [OVA257-264: SIINFEKL]) and an immunostimulatory adjuvant (CpG ODNs, TLR9 agonist) to PEG hydrogel NPs via a reduction sensitive linker. Bone-marrow derived dendritic cells (BMDCs) treated with the SIINFEKL conjugated NPs efficiently cross-presented the antigenic peptide via MHC-I surface receptor and induced proliferation of OT-I T cells. CpG ODN-conjugated NPs induced maturation of BMDCs as evidenced by the overexpression of CD80 and CD40 costimulatory receptors. Moreover, codelivery of NP conjugated SIINFEKL and CpG ODN significantly increased the frequency of IFN-gamma producing CD8+ effector T cells in mice (~6-fold improvement over soluble antigen and adjuvant). Furthermore, the NP subunit vaccine-induced effector T cells were able to kill up to 90% of the adoptively transferred antigenic peptide-loaded target cell. These results demonstrate that the reduction sensitive NP subunit vaccine elicits a potent CTL response and provide compelling evidence that this approach could be utilized to engineer particulate vaccines to deliver tumor or pathogen associated antigenic peptides to harness the immune system to fight against cancer and infectious diseases. PMID- 27551743 TI - Subclinical Hypothyroidism and Metabolic Syndrome: A Common Association by Chance or a Cardiovascular Risk Driver? AB - The metabolic syndrome (MS) and subclinical hypothyroidism (SCH) are highly prevalent in the general population. Cross-sectional epidemiological data suggest that a mutual association exists between the two, although the cause-effect relationship remains poorly elucidated. As SCH raises cholesterol, blood pressure, and visceral fat, it is easy to understand why it associates with MS. Rather, the reasons whereby MS patients are at higher risk for SCH are less apparent. Some studies have reported that SCH is itself characterized by high cardiovascular risk. Therefore, the coexistence of SCH and MS may identify subjects at a particularly high risk for future cardiovascular events. Recent data published in Metabolic Syndrome and Related Disorders indicate that carotid intima-media thickness, a marker of initial atherosclerosis and a possible predictor of future events, is higher in patients with both SCH and MS than in the presence of each condition alone. In this Editorial, we discuss the clinical implications of SCH and MS association and the interpretation of such recent findings. PMID- 27551744 TI - Detailed Chemical Composition of Condensed Tannins via Quantitative (31)P NMR and HSQC Analyses: Acacia catechu, Schinopsis balansae, and Acacia mearnsii. AB - The chemical composition of Acacia catechu, Schinopsis balansae, and Acacia mearnsii proanthocyanidins has been determined using a novel analytical approach that rests on the concerted use of quantitative (31)P NMR and two-dimensional heteronuclear NMR spectroscopy. This approach has offered significant detailed information regarding the structure and purity of these complex and often elusive proanthocyanidins. More specifically, rings A, B, and C of their flavan-3-ol units show well-defined and resolved absorbance regions in both the quantitative (31)P NMR and HSQC spectra. By integrating each of these regions in the (31)P NMR spectra, it is possible to identify the oxygenation patterns of the flavan-3-ol units. At the same time it is possible to acquire a fingerprint of the proanthocyanidin sample and evaluate its purity via the HSQC information. This analytical approach is suitable for both the purified natural product proanthocyanidins and their commercial analogues. Overall, this effort demonstrates the power of the concerted use of these two NMR techniques for the structural elucidation of natural products containing labile hydroxy protons and a carbon framework that can be traced out via HSQC. PMID- 27551745 TI - Correction: Introgression of opaque2 into Waxy Maize Causes Extensive Biochemical and Proteomic Changes in Endosperm. AB - [This corrects the article DOI: 10.1371/journal.pone.0158971.]. PMID- 27551747 TI - Cost-Efficient and Multi-Functional Secure Aggregation in Large Scale Distributed Application. AB - Secure aggregation is an essential component of modern distributed applications and data mining platforms. Aggregated statistical results are typically adopted in constructing a data cube for data analysis at multiple abstraction levels in data warehouse platforms. Generating different types of statistical results efficiently at the same time (or referred to as enabling multi-functional support) is a fundamental requirement in practice. However, most of the existing schemes support a very limited number of statistics. Securely obtaining typical statistical results simultaneously in the distribution system, without recovering the original data, is still an open problem. In this paper, we present SEDAR, which is a SEcure Data Aggregation scheme under the Range segmentation model. Range segmentation model is proposed to reduce the communication cost by capturing the data characteristics, and different range uses different aggregation strategy. For raw data in the dominant range, SEDAR encodes them into well defined vectors to provide value-preservation and order-preservation, and thus provides the basis for multi-functional aggregation. A homomorphic encryption scheme is used to achieve data privacy. We also present two enhanced versions. The first one is a Random based SEDAR (REDAR), and the second is a Compression based SEDAR (CEDAR). Both of them can significantly reduce communication cost with the trade-off lower security and lower accuracy, respectively. Experimental evaluations, based on six different scenes of real data, show that all of them have an excellent performance on cost and accuracy. PMID- 27551746 TI - A Robust Actin Filaments Image Analysis Framework. AB - The cytoskeleton is a highly dynamical protein network that plays a central role in numerous cellular physiological processes, and is traditionally divided into three components according to its chemical composition, i.e. actin, tubulin and intermediate filament cytoskeletons. Understanding the cytoskeleton dynamics is of prime importance to unveil mechanisms involved in cell adaptation to any stress type. Fluorescence imaging of cytoskeleton structures allows analyzing the impact of mechanical stimulation in the cytoskeleton, but it also imposes additional challenges in the image processing stage, such as the presence of imaging-related artifacts and heavy blurring introduced by (high-throughput) automated scans. However, although there exists a considerable number of image based analytical tools to address the image processing and analysis, most of them are unfit to cope with the aforementioned challenges. Filamentous structures in images can be considered as a piecewise composition of quasi-straight segments (at least in some finer or coarser scale). Based on this observation, we propose a three-steps actin filaments extraction methodology: (i) first the input image is decomposed into a 'cartoon' part corresponding to the filament structures in the image, and a noise/texture part, (ii) on the 'cartoon' image, we apply a multi-scale line detector coupled with a (iii) quasi-straight filaments merging algorithm for fiber extraction. The proposed robust actin filaments image analysis framework allows extracting individual filaments in the presence of noise, artifacts and heavy blurring. Moreover, it provides numerous parameters such as filaments orientation, position and length, useful for further analysis. Cell image decomposition is relatively under-exploited in biological images processing, and our study shows the benefits it provides when addressing such tasks. Experimental validation was conducted using publicly available datasets, and in osteoblasts grown in two different conditions: static (control) and fluid shear stress. The proposed methodology exhibited higher sensitivity values and similar accuracy compared to state-of-the-art methods. PMID- 27551748 TI - Medication Adherence Patterns after Hospitalization for Coronary Heart Disease. A Population-Based Study Using Electronic Records and Group-Based Trajectory Models. AB - OBJECTIVE: To identify adherence patterns over time and their predictors for evidence-based medications used after hospitalization for coronary heart disease (CHD). PATIENTS AND METHODS: We built a population-based retrospective cohort of all patients discharged after hospitalization for CHD from public hospitals in the Valencia region (Spain) during 2008 (n = 7462). From this initial cohort, we created 4 subcohorts with at least one prescription (filled or not) from each therapeutic group (antiplatelet, beta-blockers, ACEI/ARB, statins) within the first 3 months after discharge. Monthly adherence was defined as having >=24 days covered out of 30, leading to a repeated binary outcome measure. We assessed the membership to trajectory groups of adherence using group-based trajectory models. We also analyzed predictors of the different adherence patterns using multinomial logistic regression. RESULTS: We identified a maximum of 5 different adherence patterns: 1) Nearly-always adherent patients; 2) An early gap in adherence with a later recovery; 3) Brief gaps in medication use or occasional users; 4) A slow decline in adherence; and 5) A fast decline. These patterns represented variable proportions of patients, the descending trajectories being more frequent for the beta-blocker and ACEI/ARB cohorts (16% and 17%, respectively) than the antiplatelet and statin cohorts (10% and 8%, respectively). Predictors of poor or intermediate adherence patterns were having a main diagnosis of unstable angina or other forms of CHD vs. AMI in the index hospitalization, being born outside Spain, requiring copayment or being older. CONCLUSION: Distinct adherence patterns over time and their predictors were identified. This may be a useful approach for targeting improvement interventions in patients with poor adherence patterns. PMID- 27551749 TI - Relations between Concurrent Longitudinal Changes in Cognition, Depressive Symptoms, Self-Rated Health and Everyday Function in Normally Aging Octogenarians. AB - Ability to predict and prevent incipient functional decline in older adults may help prolong independence. Cognition is related to everyday function and easily administered, sensitive cognitive tests may help identify at-risk individuals. Factors like depressive symptoms and self-rated health are also associated with functional ability and may be as important as cognition. The purpose of this study was to investigate the relationship between concurrent longitudinal changes in cognition, depression, self-rated health and everyday function in a well defined cohort of healthy 85 year olds that were followed-up at the age of 90 in the Elderly in Linkoping Screening Assessment 85 study. Regression analyses were used to determine if cognitive decline as assessed by global (the Mini-Mental State Examination) and domain specific (the Cognitive Assessment Battery, CAB) cognitive tests predicted functional decline in the context of changes in depressive symptoms and self-rated health. Results showed deterioration in most variables and as many as 83% of these community-dwelling elders experienced functional difficulties at the age of 90. Slowing-down of processing speed as assessed by the Symbol Digits Modality Test (included in the CAB) accounted for 14% of the variance in functional decline. Worsening self-rated health accounted for an additional 6%, but no other variables reached significance. These results are discussed with an eye to possible preventive interventions that may prolong independence for the steadily growing number of normally aging old-old citizens. PMID- 27551750 TI - Mortality, Morbidity and Health-Seeking Behaviour during the Ebola Epidemic 2014 2015 in Monrovia Results from a Mobile Phone Survey. AB - Between March 2014 and July 2015 at least 10,500 Ebola cases including more than 4,800 deaths occurred in Liberia, the majority in Monrovia. However, official numbers may have underestimated the size of the outbreak. Closure of health facilities and mistrust in existing structures may have additionally impacted on all-cause morbidity and mortality. To quantify mortality and morbidity and describe health-seeking behaviour in Monrovia, Medecins sans Frontieres (MSF) conducted a mobile phone survey from December 2014 to March 2015. We drew a random sample of households in Monrovia and conducted structured mobile phone interviews, covering morbidity, mortality and health-seeking behaviour from 14 May 2014 until the day of the survey. We defined an Ebola-related death as any death meeting the Liberian Ebola case definition. We calculated all-cause and Ebola-specific mortality rates. The sample consisted of 6,813 household members in 905 households. We estimated a crude mortality rate (CMR) of 0.33/10,000 persons/day (95%CI:0.25-0.43) and an Ebola-specific mortality rate of 0.06/10,000 persons/day (95%-CI:0.03-0.11). During the recall period, 17 Ebola cases were reported including those who died. In the 30 days prior to the survey 277 household members were reported sick; malaria accounted for 54% (150/277). Of the sick household members, 43% (122/276) did not visit any health care facility. The mobile phone-based survey was found to be a feasible and acceptable alternative method when data collection in the community is impossible. CMR was estimated well below the emergency threshold of 1/10,000 persons/day. Non-Ebola-related mortality in Monrovia was not higher than previous national estimates of mortality for Liberia. However, excess mortality directly resulting from Ebola did occur in the population. Importantly, the small proportion of sick household members presenting to official health facilities when sick might pose a challenge for future outbreak detection and mitigation. Substantial reported health-seeking behaviour outside of health facilities may also suggest the need for adapted health messaging and improved access to health care. PMID- 27551751 TI - MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury. AB - Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region. In the crushed nerve, MHC-I protein levels increased 2 weeks after lesion (wal) and progressively decreased over the next eight weeks. The same kinetics were observed for infiltrating cytotoxic T lymphocytes (CTLs) but not for PirB expression, which continuously increased. Both MHC-I and PirB were found in macrophages and Schwann cells but rarely in axons. Interestingly, at 8 wal, PirB was mainly restricted to the myelin sheath. Our findings reinforce the participation of MHC-I and PirB in CNS plasticity events. In contrast, opposing expression levels of these molecules were found in the PNS, so that MHC-I and PirB seem to be mostly implicated in antigen presentation to CTLs and axon myelination, respectively. PMID- 27551752 TI - Breast cancer incidence among female flight attendants: exposure-response analyses. AB - OBJECTIVE: The aim of this study was to examine the association of breast cancer incidence with cosmic radiation dose and circadian rhythm disruption in a cohort of 6093 US female flight attendants. METHODS: The association of breast cancer risk with cumulative cosmic radiation dose, time spent working during the standard sleep interval, and time zones crossed (all lagged by ten years), adjusted for non-occupational breast cancer risk factors, was evaluated using Cox regression. Individual exposure estimates were derived from work history data and domicile- and era-specific exposure estimates. Breast cancers were identified from telephone interviews and state cancer registries, and covariate data were obtained from telephone interviews. RESULTS: Breast cancer incidence in the overall cohort was not associated with exposure. Positive associations in breast cancer incidence were observed with all three exposures only among the 884 women with parity of >=3. Adjusted excess relative risks for women with parity of >=3 were 1.6 [95% confidence interval (95% CI) 0.14-6.6], 0.99 (95% CI -0.04-4.3), and 1.5 (95% CI 0.14-6.2) per 10 mGy, per 2000 hours spent working in the standard sleep interval, and per 4600 time zones crossed (the approximate means of the fourth exposure quintiles among breast cancer cases), respectively. CONCLUSIONS: Positive exposure-response relations, although observed only in a small subset of the cohort, were robust. Future studies of breast cancer incidence among other workers with circadian rhythm disruption should assess interaction with parity to see if our findings are confirmed. PMID- 27551753 TI - Involuntary admissions in Italy: the impact of seasonality. AB - OBJECTIVE: The aim of this study is to assess the prevalence of involuntary admissions with regard to seasonality and clinical associated features, in a sample of patients admitted to a psychiatric unit in a period of 24 months. METHODS: All subjects consecutively admitted to the Psychiatric Inpatient Unit of the San Luigi Gonzaga Hospital, Orbassano (University of Turin, Italy) from September 2013 to August 2015 were recruited. Socio-demographic and clinical characteristics were collected. RESULTS: Seven hundred and thirty admissions in psychiatric ward were recognized. The prevalence of involuntary admission was 15.4%. Patients with involuntary hospitalizations showed a higher education level, a higher prevalence of admission in spring/summer with a significant peak in June, a longer duration of hospitalization and a lower suicide ideation. Among involuntary admissions, physical restraint and suicide attempts were more prevalent during spring compared to the other seasons. CONCLUSIONS: Seasonality has an important role in the psychopathology of psychiatric disorders, particularly in bipolar and related disorder, and may represent an influencing factor in hospital admissions and hospitalizations. Seasonal pattern must be considered while managing diagnosis and treatment of mental disorders, with regard to prevention and psychoeducation of patients. PMID- 27551754 TI - Icariin attenuated oxidative stress induced-cardiac apoptosis by mitochondria protection and ERK activation. AB - Our previous study showed that Icariin (ICA) has anti-cardiac hypertrophy effect in rats with an unknown mechanism. In the present study, we aimed to clarify the cardiac protective effect and mechanism of ICA in vitro. H9C2 cardiac myocytes were incubated with H2O2 to build up the oxidative stress injury model. The results showed that pre-treatment of ICA protected cells against the toxicity induced by H2O2. H2O2 treatment significantly reduced H2O2-induced apoptosis, evidenced by lower Annexin V/PI stained cells and less PARP and caspase-3/9 activation. Mitochondria membrane potential (MMP) dissipation occurred following the exposure of H2O2, which could be prevented by ICA treatment. Moreover, Ca2+ homeostasis was preserved by ICA and ROS generation was significantly suppressed by ICA incubation. Interestingly, ICA treatment increased the phosphorylation of upstream ERK mitogen-activated protein kinase (MAPK) while ERK inhibitor U1026 could reverse the protective effect of ICA. Overall, ICA seems to protect the cardiac cells from oxidative stress injury through ROS scavenge and stimulation of ERK pathway which may explain its effects in vivo. PMID- 27551755 TI - Improvement of ursolic and oleanolic acids' antitumor activity by complexation with hydrophilic cyclodextrins. AB - Ursolic and oleanolic acids have been brought into the spotlight of research due to their chemopreventive, anti-inflammatory and immunomodulatory properties. The most important disadvantage of ursolic and oleanolic acids is their weak water solubility which limits their bioavailability. Pentacyclic triterpenes can form inclusion complexes with different types of cyclodextrins which provide the hydrophilic matrix requested for the molecular dispersion of drugs in order to become more water soluble. The aim of the current study is the complexation of ursolic and oleanolic acids with hydrophilic cyclodextrins in order to achieve an improvement of their pharmacological effect. After the virtual screening of the binding affinities between ursolic and oleanolic acids and various cyclodextrins, 2-hydroxypropyl-beta-cyclodextrin and 2-hydroxypropil-gamma-cyclodextrin were selected as host-molecules for the inclusion complexation. Using the scanning electron microscopy, differential scanning calorimetry and X-ray diffraction the formation of real inclusion complexes between ursolic and oleanolic acids and the two cyclodextrins was confirmed. The anti-proliferative potential of the complexes was tested in vitro on several melanoma cell lines, using the pure compounds as reference. The complexes exhibited higher in vitro anti proliferative activity as compared to the pure compounds; this improvement was significant for ursolic acid complexes, the highest activity being reported for the 2-hydroxypropil-gamma-cyclodextrin complex. Weaker results were recorded for the oleanolic acid complexes where 2-hydroxypropyl-beta-cyclodextrin proved to be the most fitted inclusion partner. The entrapment of the two active compounds inside ramified hydrophilic cyclodextrins proved to be a suitable option to increase their anti-proliferative activity. PMID- 27551756 TI - Ossotide promotes cell differentiation of human osteoblasts from osteogenesis imperfecta patients by up-regulating miR-145. AB - Ossotide as an effective bone formation compound preparation has been proved to promote osteoblasts differentiation. MiR-145 is significantly decreased in osteogenesis imperfecta (OI) patients, but it is still unknown whether ossotide performed its effect by regulating miR-145. In this study, we investigated the effect of ossotide on regulating miR-145 expression and osteoblasts differentiation. The primary osteoblasts cells were isolated from OI patients and then cultured with different concentrations (0, 25, 50, 100, 200MUg/l) of ossotide. The cell proliferation was detected with CCK-8 Elisa kit after ossotide treatment. The level of miR-145 expression was determined using qRT-PCR. In order to study whether ossotide up regulated miR-145, miR-145 mimic and miR-145 inhibitor were used to up regulate and down regulate the miR-145 levels in osteoblasts. The expressions of Runx2, Osx, beta-catenin, TCF-1 were detected using Western blot and qRT-PCR. We observed that miR-145 was up regulated by ossotide treatment in miR-145 mimic or miR-145 inhibitor treated osteoblasts. What's more, up regulated miR-145 increased the expression of osteoblasts differentiation regulated protein Runx2 and Osx. In addition, Wnt signaling related beta-catenin, TCF-1 were activated by up-regulated miR-145 which was induced by ossotide treatment. In summary, ossotide induced cell differentiation and Wnt signaling activation in osteoblasts by up regulating miR-145. PMID- 27551757 TI - Protective effects of Solanum cernuum extract against chromosomal and genomic damage induced by methyl methanesulfonate in Swiss mice. AB - Solanum cernuum Vell is a Brazilian shrub or small tree, restricted to Southeast states of the country. The leaves are commercialized as "panaceia" and indicated for the treatment of urinary disorders, gonorrhea, scabies, skin diseases and as desobstruent, diuretic and antiarrhythmic. The hydroalcholic extract is active in the treatment of gastric ulcer. The aim of this study was to evaluate the genotoxic and antigenotoxic potential of S. cernuum hydroalcoholic extract (SC) in Swiss mice by micronucleus and comet assays. The animals were treated by gavage with the doses of 500, 1000 and 2000mg/kg body weight (b.w.). For antigenotoxicity assessment, the doses of 15, 30, 60, 120 and 240mg/kg b.w SC were administered simultaneously with the mutagen methyl methanesulfonate (MMS, 40mg/kg b.w., i.p.). The results showed that the SC was not genotoxic in both micronucleus and comet assays. On the other hand, the treatment with the lowest dose of SC (15mg/kg b.w.) plus MMS showed a statistically significant reduction in the frequency of micronuclei compared to treatment only with MMS. For the comet assay, significant reduction in extensions of DNA damage was observed in all treatments with SC combined with MMS in comparison with only MMS. The antigenotoxic activity observed for the SC may be due to the antioxidant potential of the compounds present in the extract such as guanidine alkaloids and flavonoids. PMID- 27551758 TI - The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway. AB - OBJECTIVE: This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. METHODS: MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into following groups: control group, control+tanshinone IIA (50MUM) group, H/R model group, H/R+tanshinone IIA (5MUM) group, H/R+tanshinone IIA (50MUM) pre-treatment group, H/R+AG490 (50MUM) pre-treatment group and H/R+AG490 (50MUM)+tanshinone IIA (50MUM) pre-treatment group. MTT assay, TUNEL staining and flow cytometry were used to measure the cellular viability and apoptosis. Western-blot were performed to detect protein expressions in JAK2/STAT3 signaling pathway. RESULTS: Compared with control group, H/R group showed decreased cell viability, increased apoptosis rate, increased proportions of cells into G0/G1 phase, decreased proportions of cells in S phase and G2/M phase, as well as up-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, and down-regulated Bcl-2 expression (all P<0.05). Compared with H/R group, H/R+tanshinone IIA (5MUM) group, H/R+tanshinone IIA (50MUM) group H/R+AG490 (50MUM) group and H/R+AG490 (50MUM)+tanshinone IIA (50MUM) group had increased cell viability, decreased apoptosis rate, reduced proportions of cells into G0/G1 phase, elevated proportions of cells in S phase and G2/M phase, as well as down-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, elevated expression of Bcl-2 (all P<0.05). The most remarkable changes were observed in H/R+AG490 (50MUM)+tanshinone IIA (50MUM) group. CONCLUSION: Tanshinone IIA may attenuate H/R-induced MMEC apoptosis in rats by inhibiting the JAK2/STAT3 signaling pathway and regulating the expressions of p53, Bax, Caspase-3 and Bcl-2, which may provide a protective effect of tanshinone IIA for MMECs. PMID- 27551759 TI - 47kDa isoform of Annexin A7 affecting the apoptosis of mouse hepatocarcinoma cells line. AB - Our previous studies have shown that Annexin A7 is associated with the cell proliferation and apoptosis. Both the isoforms 47kDa and 51kDa of Annexin A7 are expressed in liver cancer cells. This study aimed at elucidating which isoform of Annexin A7 affects the cell apoptosis and how to affect in the hepatocarcinoma cell line. The results showed that Annexin A7 co-immunoprecipitated with Bcl2 and co-located in the cytoplasm and the mitochondria. Therein, the regulated 47kDa isoform of Annexin A7 altered the expression of Bcl2 and the mitochondrial membrane potential. These results indicate that 47kDa isoform of Annexin A7 could associated with the apoptosis of Hca-P cells through its interaction with Bcl2. PMID- 27551760 TI - The inhibition of macrophage foam cell formation by tetrahydroxystilbene glucoside is driven by suppressing vimentin cytoskeleton. AB - Macrophage foam cell formation triggered by oxLDL is an important event that occurs during the development of atherosclerosis. 2,3,5,4'-Tetrahydroxystilbene-2 O-beta-d-glucoside (TSG) exhibits significant anti-atherosclerotic activity. Herein we used U937 cells induced by PMA and oxLDL in vitro to investigate the inhibitory effects of TSG on U937 differentiation and macrophage foam cell formation. TSG pretreatment markedly inhibited cell differentiation induced by PMA, macrophage apoptosis and foam cell formation induced by oxLDL. The inhibition of vimentin expression and cleavage was involved in these inhibitory effects of TSG. The suppression of vimentin by siRNA in U937 significantly inhibited cell differentiation, apoptosis and foam cell formation. Using inhibitors for TGFbetaR1 and PI3K, we found that vimentin production in U937 cells is regulated by TGFbeta/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG pretreatment inhibited both the expression of TGFbeta1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by PMA and oxLDL. Furthermore, TSG attenuated the induced caspase-3 activation and adhesion molecules levels by PMA and oxLDL. PMA and oxLDL increased the co-localization of vimentin with ICAM-1, which was attenuated by pretreatment with TSG. These results suggest that TSG inhibits macrophage foam cell formation through suppressing vimentin expression and cleavage, adhesion molecules expression and vimentin-ICAM-1 co-localization. The interruption of TGFbeta/Smad pathway and caspase-3 activation is responsible for the downregulation of TSG on vimentin expression and degradation, respectively. PMID- 27551761 TI - Interactions between medications employed in treating benign prostatic hyperplasia and food - A short review. AB - Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. BPH symptoms include frequent urination, urgent tenesmus and urination at night, a weak and interrupted urine flow and a sense of incomplete emptying of the bladder. Alpha- 1 adrenergic receptor antagonists and 5 alpha-reductase inhibitors form the most important groups of medications employed in BPH. Appropriately managed BPH patients shall be subject to counselling on interactions between agents belonging to these groups, and on particular components of the food they have. The present review has been aimed at assessing potential effects of consumed food, alcohol and fruit juices on the pharmacokinetics and pharmacodynamics of medications for benign prostatic hyperplasia. The authors reviewed the English PubMed database covering the years 1991-2015. Additionally, a digital version of Stockley Drugs Interaction and other electronic databases such as drugs.com and Medscape were also researched; characterisation charts for particular medical products were also analyzed. Pharmacokinetics of extended-release forms of alfuzosin, doxazosin, tamsulosin and silodosin is well known to be food-sensitive. Alfuzosin, tamsulosin and silodosin due to their likely interaction with grapefruit juice and citrus fruits, may intensify adverse effects of the drugs. Alpha-1 adrenergic receptor antagonists are known to interact with alcohol, leading to orthostatic hypotension. For 5 alpha-reductase inhibitors, such as finasteride, or dutasteride, the pharmacokinetic effect due to consumed food is of no clinical importance and thus they may be taken regardless of meals. As in general grapefruit juice and alcohol tend to significantly affect the efficacy and safety of the applied drug therapy, it is highly advisable to be knowledgeable on the subject in order to educate patients. PMID- 27551762 TI - Biphenyl tetrazole-thiazolidinediones as novel bacterial peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study. AB - Herein, we report the synthesis and screening of biphenyl tetrazole thiazolidinediones 14(a-j) as bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC50 value=16.25MUM), 14c (IC50 value=18.00MUM) and 14h (IC50 value=17.25MUM) had shown good PDF inhibition activity. The compounds 14b (MIC range=20.75-35.41MUg/mL), 14c (MIC range=19.41-26.00MUg/mL) and 14d (MIC range=8.41-8.58MUg/mL) had also shown potent antibacterial activity when compared with standard ciprofloxacin (MIC range=25-50MUg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 14(a-j) were docked against PDF enzyme of E. coli and compounds exhibited good binding properties. The results suggest that this class of compounds have been potential for development and use in a future as antibacterial drugs. PMID- 27551763 TI - Application of nanoparticle technology in the treatment of Systemic lupus erythematous. AB - Systemic lupus erythematous (SLE) is a chronic heterogeneous multisystem autoimmune disease characterized by loss of tolerance to self-antigens and production of numerous autoantibodies. Current therapeutic approaches used to treat inflammatory autoimmune diseases are associated with debilitating side effects. In spite of significant advances in therapeutic options and increased understanding of the pathogenesis, novel therapeutic approaches are needed for treatment of SLE. Nanoparticle-based delivery systems that selectively deliver drugs to inflamed tissue or specific cell have the potential to improve drug delivery. This article reviews recent nanotechnology-based therapeutics strategies that are being developed for the treatment of SLE. PMID- 27551764 TI - Fisetin inhibits laryngeal carcinoma through regulation of AKT/NF-kappaB/mTOR and ERK1/2 signaling pathways. AB - Targeting cancer cells is crucial for improving the efficiency of laryngeal cancer treatment. However, the signaling pathway and therapeutic strategy, related to the tumor, still need further research. Dietary flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through regulating cell cycle, apoptosis, angiogenesis, invasion and metastasis without causing any toxicity to normal cells. PI3K/AKT and ERK1/2 have been known as essential signaling pathways to modulate cell proliferation, apoptosis as well as autophagy via mTOR, Caspase-3 and NF-kappaB signals. In our study, flow cytometry and western blot assays suggested that apoptosis was induced by fisetin administration, promoting Caspase-3 expressions by regulating PI3K/AKT/NF-kappaB. Additionally, fisetin suppressed TU212 cells proliferation, which was linked with ERK1/2 inactivation. Further, the activation of PI3K/AKT-regulated mTOR was inhibited by fisetin, leading to transcription suppression and proliferation inhibition of TU212 cells. In vivo studies also showed that the tumor volume and weight of nude mice were reduced for fisetin use with KI-67 decrease and LC3II increase in tumor tissue samples. Together, our data indicated that fisetin had a potential role in controlling human laryngeal cancer through inhibiting tumor cell proliferation, inducing apoptosis and autophagy regulated by ERK1/2 and AKT/NF-kappaB/mTOR signaling pathways, which might provide a therapeutic strategy for laryngeal cancer inhibition in future. PMID- 27551765 TI - MicroRNA-383 is a tumor suppressor and potential prognostic biomarker in human non-small cell lung caner. AB - PURPOSE: The purpose of this study is to examine the expression and clinical significance microRNA-383 (miR-383) in non-small cell lung cancer (NSCLC) both in vitro and in vivo. METHODS: Tumorous miR-383 expressions were compared between NSCLC cell lines and normal lung cells. MiR-383 was upregulated in A549 and H596 cells to evaluate its tumor suppressive effect on NSCLC proliferation, invasion and migration in vitro. MiR-383 expression was also compared between 139-paired clinical NSCLC tissues and their adjacent non-carcinoma lung tissues, as well as between early-stage NSCLC tissues and advanced-stage NSCLC tissues. Correlation between tumorous miR-383 expression and NSCLC patients' clinicopathological features and overall survival (OS) were also statistically analyzed. RESULTS: MiR 383 was significantly downregulated in NSCLC cell lines. MiR-383 overexpression reduced proliferation, invasion and migration of A549 and H596 cells. In clinical samples, miR-383 was also found to be markedly downregulated in NSCLC carcinomas than in non-carcinoma lung tissues, and in advanced-stage carcinomas than in early-stage carcinomas. It was also found low tumorous miR-383 expression was significantly associated with NSCLC patients' poor prognosis, including advanced TNM stages, positive lymph node metastasis, and shorter OS. CONCLUSION: Endogenous miR-383 is a functional tumor suppressor in NSCLC. It may also serve as an independent prognostic factor for patients with NSCLC. PMID- 27551766 TI - Regulation of oncogenic genes by MicroRNAs and pseudogenes in human lung cancer. AB - Lung cancer is one of the most common mortal cancer types both for men and women. Several different biomarkers have been analyzed to reveal lung cancer prognosis pathways for developing efficient therapeutics and diagnostic agents. microRNAs (miRNAs) and pseudogenes are critical biomarkers in lung cancer and alteration of their expression levels has been identified in each step of lung cancer tumorigenesis. miRNAs and pseudogenes are crucial gene regulators in normal cells as well as in lung cancer cells, and they have both oncogenic and tumor suppressive roles in lung cancer tumorigenesis. In this study, we have determined the relationship between lung cancer related oncogenes and miRNAs along with pseudogenes in lung cancer, and the results indicate their potential as biological markers for diagnostic and therapeutic purposes. PMID- 27551767 TI - Protective effects of a blueberry extract in acute inflammation and collagen induced arthritis in the rat. AB - Here we investigated the anti-inflammatory effect of a blueberry extract in the carrageenan-induced paw edema model and collagen-induced arthritis model, both in rats. Along with the chemical characterization of the phenolic content of the fruits and extract, the antioxidant potential of the extract, the cellular antioxidant activity and the effects over neutrophils' oxidative burst, were studied in order to provide a mechanistic insight for the anti-inflammatory effects observed. The extract significantly inhibited paw edema formation in an acute model the rat. Our results also demonstrate that the standardized extract had pharmacological activity when administered orally in the collagen-induced arthritis model in the rat and was able to significantly reduce the development of clinical signs of arthritis and the degree of bone resorption, soft tissue swelling and osteophyte formation, consequently improving articular function in treated animals. PMID- 27551768 TI - Versatile Reactivity and Theoretical Evaluation of Mono- and Dinuclear Oxidovanadium(V) Compounds of Aroylazines: Electrogeneration of Mixed-Valence Divanadium(IV,V) Complexes. AB - The substituted hydrazones H2L(1-4) (L(1-4) = dibasic tridentate ONO(2-) donor ligands) obtained by the condensation of 2-hydroxy-1-naphthaldehyde and 2 aminobenzoylhydrazine (H2hnal-abhz) (H2L(1)) , 2-hydroxy-1-naphthaldehyde and 2 hydroxybenzoylhydrazine (H2hnal-hbhz) (H2L(2)), 2-hydroxy-1-acetonaphthone and benzoylhydrazine (H2han-bhz) (H2L(3)), or 2-hydroxy-1-acetonaphthone and 2 aminobenzoylhydrazine (H2han-abhz) (H2L(4)) are prepared and characterized. Reaction of ammonium vanadate with the appropriate H2L(1-4) results in the formation of oxidoethoxidovanadium(V) [V(V)O(OEt)(L(1-4))] (1-4) complexes. All compounds are characterized in the solid state and in solution by spectroscopic techniques (IR, UV-vis, (1)H, (13)C, and (51)V NMR, and electrospray ionization mass spectrometry). Single-crystal X-ray diffraction analysis of 1, 3, and 4 confirms the coordination of the corresponding ligands in the dianionic (ONO(2-)) enolate tautomeric form. In solution, the structurally characterized [V(V)O(OEt)(L)] compounds transform into the monooxido-bridged divanadium(V,V) [(V(V)OL)2-MU-O] complexes, with the processes being studied by IR and (1)H, (13)C, and (51)V NMR. The density functional theory (DFT) calculated Gibbs free energy of reaction 2[V(V)O(OEt)(L(4))] + H2O ? [(V(V)OL(4))2-MU-O] + 2EtOH is only 2-3 kcal mol(-1), indicating that the dinuclear complexes may form in a significant amount. The electrochemical behavior of the complexes is investigated by cyclic voltammetry, with the V(V)-V(IV) E1/2(red) values being in the range 0.27-0.44 V (vs SCE). Upon controlled potential electrolysis, the corresponding (L)(O)V(IV)-O-V(V)(O)(L) mixed-valence species are obtained upon partial reduction of the [(V(V)OL)2-MU-O] complexes formed in solution, and some spectroscopic characteristics of these dinuclear mixed-valence complexes are investigated using DFT calculations and by electron paramagnetic resonance (EPR), with the formation of V(IV)-O-V(V) species being confirmed by the observation of a 15-line pattern in the EPR spectra at room temperature. PMID- 27551769 TI - Mobile phone use and the brain cancer incidence rate in Australia. PMID- 27551770 TI - Has the incidence of brain cancer risen in Australia since the introduction of mobile phones 29 years ago? PMID- 27551771 TI - MicroRNA expression profiles in patients with acute Crimean Congo hemorrhagic fever reveal possible adjustments to cellular pathways. AB - Several viral diseases are associated with altered microRNA (miRNA) expression, which can provide vital information about how cellular pathways respond to infection. However, the miRNA profile of Crimean Congo Hemorrhagic Fever (CCHFV) infections are not known. To address this gap, we performed real-time PCR-based miRNA analysis in individuals with acute Crimean Congo Hemorrhagic Fever (CCHFV) infections, with the goal of identifying pathways that might be associated with this disease. Peripheral blood mononuclear cells were analysed in eight individuals with detectable viral RNA and compared to five healthy subjects. A total of 106 differentially expressed miRNAs were identified, of which 19 miRNAs were either fivefold prominently up- or down-regulation. Several miRNAs associated with cytokine expression, some of which were previously associated with Dengue and Hantavirus infections were revealed. Moreover, possible mechanisms related to secretion of adhesion molecules and viral escape from innate immunity were identified. Pathway enrichment analyses further revealed the putative involvement of TNF-alfa, TGF-beta, MAPK, WNT, and neurotrophin signaling pathways in disease pathogenesis. J. Med. Virol. 89:417-422, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27551772 TI - Palladium-Catalyzed Norbornene-Mediated Tandem Amination/Cyanation Reaction: A Method for the Synthesis of ortho-Aminated Benzonitriles. AB - A palladium-catalyzed, norbornene-mediated tandem amination/cyanation reaction via Catellani-type C-H functionalization was developed using N-benzoyloxyamines as the amination reagent and Zn(CN)2 as the terminating agent. This transformation, in which one C-N bond and one C-C bond are formed, provides an efficient approach for the synthesis of ortho-aminated benzonitriles in one pot from easily accessible starting materials. PMID- 27551773 TI - Relationship of embodied nursing knowledge and client outcomes in home health. AB - Embodied nursing knowledge and its effects on patient outcomes are understudied in home health. The researchers performed a descriptive correlational study, in nine home health agencies in Ohio, to consider the effects of embodied nursing knowledge in expert practice in 107 registered nurses working in Medicare certified home health agencies. While statistical significance was not noted, findings of this study add to the understanding or research and the outcome improvement scores in home health. Findings also pose the question that the concepts used in acute care to improve mortality rates and patient outcome improvements may be different in home health. PMID- 27551774 TI - Asking the right questions to get the right answers: using cognitive interviews to review the acceptability, comprehension and clinical meaningfulness of patient self-report adverse event items in oncology patients. AB - BACKGROUND: Standardized reporting of treatment-related adverse events (AE) is essential in clinical trials, usually achieved by using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) reported by clinicians. Patient-reported adverse events (PRAE) may add value to clinician assessments, providing patient perspective on subjective toxicity. We developed an online patient symptom report and self-management system for real-time reporting and managing AE during cancer treatment integrated with electronic patient records (eRAPID). As part of this program we developed a patient version of the CTCAE (version 4.0), rephrasing terminology into a self-report format. We explored patient understanding of these items via cognitive interviews. MATERIAL AND METHOD: Sixty patients (33 female, 27 male) undergoing treatment were purposively sampled by age, gender and tumor group (median age 61.5, range 35-84, 12 breast, 12 gynecological, 13 colorectal, 12 lung and 11 renal). Twenty-one PRAE items were completed on a touch-screen computer. Subsequent audio-recorded cognitive interviews and thematic analysis explored patients' comprehension of items via verbal probing techniques during three interview rounds (n = 20 patients/round). RESULTS: In total 33 item amendments were made; 29% related to question comprehension, 68% response option and 3% order effects. These amendments to phrasing and language improved patient understanding but maintained CTCAE grading and key medical information. Changes were endorsed by members of a patient advisory group (N = 11). CONCLUSION: Item adaptations resulted in a bank of consistently interpreted self-report AE items for use in future research program. In-depth analysis of items through cognitive interviews is an important step towards developing an internationally valid system for PRAE, thus improving patient safety and experiences during cancer treatment. PMID- 27551775 TI - bcRep: R Package for Comprehensive Analysis of B Cell Receptor Repertoire Data. AB - Immunoglobulins, as well as T cell receptors, play a key role in adaptive immune responses because of their ability to recognize antigens. Recent advances in next generation sequencing improved also the quality and quantity of individual B cell receptors repertoire sequencing. Unfortunately, appropriate software to exhaustively analyze repertoire data from NGS platforms without limitations of the number of sequences are lacking. Here we introduce a new R package, bcRep, which offers a platform for comprehensive analyses of B cell receptor repertoires, using IMGT/HighV-QUEST formatted data. Methods for gene usage statistics, clonotype classification, as well as diversity measures, are included. Furthermore, functions to filter datasets, to do summary statistics about mutations, as well as visualization methods, are available. To compare samples in respect of gene usage, diversity, amino acid proportions, similar sequences or clones, several functions including also distance measurements, as well as multidimensional scaling methods, are provided. PMID- 27551776 TI - Proposal of a Clinical Decision Tree Algorithm Using Factors Associated with Severe Dengue Infection. AB - BACKGROUND: WHO's new classification in 2009: dengue with or without warning signs and severe dengue, has necessitated large numbers of admissions to hospitals of dengue patients which in turn has been imposing a huge economical and physical burden on many hospitals around the globe, particularly South East Asia and Malaysia where the disease has seen a rapid surge in numbers in recent years. Lack of a simple tool to differentiate mild from life threatening infection has led to unnecessary hospitalization of dengue patients. METHODS: We conducted a single-centre, retrospective study involving serologically confirmed dengue fever patients, admitted in a single ward, in Hospital Kuala Lumpur, Malaysia. Data was collected for 4 months from February to May 2014. Socio demography, co-morbidity, days of illness before admission, symptoms, warning signs, vital signs and laboratory result were all recorded. Descriptive statistics was tabulated and simple and multiple logistic regression analysis was done to determine significant risk factors associated with severe dengue. RESULTS: 657 patients with confirmed dengue were analysed, of which 59 (9.0%) had severe dengue. Overall, the commonest warning sign were vomiting (36.1%) and abdominal pain (32.1%). Previous co-morbid, vomiting, diarrhoea, pleural effusion, low systolic blood pressure, high haematocrit, low albumin and high urea were found as significant risk factors for severe dengue using simple logistic regression. However the significant risk factors for severe dengue with multiple logistic regressions were only vomiting, pleural effusion, and low systolic blood pressure. Using those 3 risk factors, we plotted an algorithm for predicting severe dengue. When compared to the classification of severe dengue based on the WHO criteria, the decision tree algorithm had a sensitivity of 0.81, specificity of 0.54, positive predictive value of 0.16 and negative predictive of 0.96. CONCLUSION: The decision tree algorithm proposed in this study showed high sensitivity and NPV in predicting patients with severe dengue that may warrant admission. This tool upon further validation study can be used to help clinicians decide on further managing a patient upon first encounter. It also will have a substantial impact on health resources as low risk patients can be managed as outpatients hence reserving the scarce hospital beds and medical resources for other patients in need. PMID- 27551777 TI - Morphometric Wing Characters as a Tool for Mosquito Identification. AB - Mosquitoes are responsible for the transmission of important infectious diseases, causing millions of deaths every year and endangering approximately 3 billion people around the world. As such, precise identification of mosquito species is crucial for an understanding of epidemiological patterns of disease transmission. Currently, the most common method of mosquito identification relies on morphological taxonomic keys, which do not always distinguish cryptic species. However, wing geometric morphometrics is a promising tool for the identification of vector mosquitoes, sibling and cryptic species included. This study therefore sought to accurately identify mosquito species from the three most epidemiologically important mosquito genera using wing morphometrics. Twelve mosquito species from three epidemiologically important genera (Aedes, Anopheles and Culex) were collected and identified by taxonomic keys. Next, the right wing of each adult female mosquito was removed and photographed, and the coordinates of eighteen digitized landmarks at the intersections of wing veins were collected. The allometric influence was assessed, and canonical variate analysis and thin-plate splines were used for species identification. Cross-validated reclassification tests were performed for each individual, and a Neighbor Joining tree was constructed to illustrate species segregation patterns. The analyses were carried out and the graphs plotted with TpsUtil 1.29, TpsRelw 1.39, MorphoJ 1.02 and Past 2.17c. Canonical variate analysis for Aedes, Anopheles and Culex genera showed three clear clusters in morphospace, correctly distinguishing the three mosquito genera, and pairwise cross-validated reclassification resulted in at least 99% accuracy; subgenera were also identified correctly with a mean accuracy of 96%, and in 88 of the 132 possible comparisons, species were identified with 100% accuracy after the data was subjected to reclassification. Our results showed that Aedes, Culex and Anopheles were correctly distinguished by wing shape. For the lower hierarchical levels (subgenera and species), wing geometric morphometrics was also efficient, resulting in high reclassification scores. PMID- 27551778 TI - Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data. AB - Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete pipeline for the analysis of single cell qPCR data that uses the mathematics behind bursty expression to develop more accurate and robust algorithms for analyzing the origin of heterogeneity in experimental samples, specifically an algorithm for clustering cells by their bursting behavior (Simulated Annealing for Bursty Expression Clustering, SABEC) and a statistical tool for comparing the kinetic parameters of bursty expression across populations of cells (Estimation of Parameter changes in Kinetics, EPiK). We applied these methods to hematopoiesis, including a new single cell dataset in which transcription factors (TFs) involved in the earliest branchpoint of blood differentiation were individually up- and down-regulated. We could identify two unique sub-populations within a seemingly homogenous group of hematopoietic stem cells. In addition, we could predict regulatory mechanisms controlling the expression levels of eighteen key hematopoietic transcription factors throughout differentiation. Detailed information about gene regulatory mechanisms can therefore be obtained simply from high throughput single cell gene expression data, which should be widely applicable given the rapid expansion of single cell genomics. PMID- 27551779 TI - Microbial Diversity Indexes Can Explain Soil Carbon Dynamics as a Function of Carbon Source. AB - Mathematical models do not explicitly represent the influence of soil microbial diversity on soil organic carbon (SOC) dynamics despite recent evidence of relationships between them. The objective of the present study was to statistically investigate relationships between bacterial and fungal diversity indexes (richness, evenness, Shannon index, inverse Simpson index) and decomposition of different pools of soil organic carbon by measuring dynamics of CO2 emissions under controlled conditions. To this end, 20 soils from two different land uses (cropland and grassland) were incubated with or without incorporation of 13C-labelled wheat-straw residue. 13C-labelling allowed us to study residue mineralisation, basal respiration and the priming effect independently. An innovative data-mining approach was applied, based on generalized additive models and a predictive criterion. Results showed that microbial diversity indexes can be good covariates to integrate in SOC dynamics models, depending on the C source and the processes considered (native soil organic carbon vs. fresh wheat residue). Specifically, microbial diversity indexes were good candidates to help explain mineralisation of native soil organic carbon, while priming effect processes seemed to be explained much more by microbial composition, and no microbial diversity indexes were found associated with residue mineralisation. Investigation of relationships between diversity and mineralisation showed that higher diversity, as measured by the microbial diversity indexes, seemed to be related to decreased CO2 emissions in the control soil. We suggest that this relationship can be explained by an increase in carbon yield assimilation as microbial diversity increases. Thus, the parameter for carbon yield assimilation in mathematical models could be calculated as a function of microbial diversity indexes. Nonetheless, given limitations of the methods used, these observations should be considered with caution and confirmed with more experimental studies. Overall, along with other studies on relationships between microbial community composition and SOM dynamics, this study suggests that overall measures of microbial diversity may constitute relevant ways to include microbial diversity in models of SOM dynamics. PMID- 27551780 TI - Hydrolysis rate constants at 10-25 degrees C can be more than doubled by a short anaerobic pre-hydrolysis at 35 degrees C. AB - Hydrolysis is the first step of the anaerobic digestion of complex wastewater and considered as the rate limiting step especially at low temperature. Low temperature (10-25 degrees C) hydrolysis was investigated with and without application of a short pre-hydrolysis at 35 degrees C. Batch experiments were executed using cellulose and tributyrin as model substrates for carbohydrates and lipids. The results showed that the low temperature anaerobic hydrolysis rate constants increased by a factor of 1.5-10, when the short anaerobic pre hydrolysis at 35 degrees C was applied. After the pre-hydrolysis phase at 35 degrees C and decreasing the temperature, no lag phase was observed in any case. Without the pre-hydrolysis, the lag phase for cellulose hydrolysis at 35-10 degrees C was 4-30 days. Tributyrin hydrolysis showed no lag phase at any temperature. The hydrolysis efficiency of cellulose increased from 40 to 62%, and from 9.6 to 40% after 9.1 days at 15 and 10 degrees C, respectively, when the pre-hydrolysis at 35 degrees C was applied. The hydrolysis efficiency of tributyrin at low temperatures with the pre-hydrolysis at 35 degrees C was similar to those without the pre-hydrolysis. The hydrolytic activity of the supernatant collected from the digestate after batch digestion of cellulose and tributyrin at 35 degrees C was higher than that of the supernatants collected from the low temperature (<=25 degrees C) digestates. PMID- 27551781 TI - The inhibitory effects of reject water on nitrifying populations grown at different biofilm thickness. AB - Suppression of nitrite oxidizing bacteria (NOB) is of vital importance to achieve successful, energy efficient, mainstream anammox processes for wastewater treatment. In this study, biofilm carriers from a fully nitrifying MBBR system, fed with mainstream wastewater, were temporarily exposed to reject water from sludge dewatering, to evaluate this as a possible strategy to inhibit NOB and achieve nitrite production under realistic conditions. Two different carrier types were compared, in which biofilm thickness was maintained at approximately 400 and 50 MUm, respectively, and reject treatment was tested at different exposure time and loading rates. Reject exposure almost always resulted in an increased nitrite production in the thinner biofilm, and overall, nitrifiers growing in the thin biofilm were more sensitive than those grown in the thicker biofilm. The effect from reject exposure remained in the systems for four days after returning to mainstream operation, with nitrite production gradually increasing for three days. Increased concentrations of free ammonia correlated with reject exposure and may be the cause of inhibition, although other factors cannot be excluded. PMID- 27551782 TI - Complete Mitochondrial Genome of the Citrus Spiny Whitefly Aleurocanthus spiniferus (Quaintance) (Hemiptera: Aleyrodidae): Implications for the Phylogeny of Whiteflies. AB - In this study, we sequenced the complete mitochondrial genome (15,220 bp) of the citrus spiny whitefly, Aleurocanthus spiniferus (Quaintance), a well-known pest from the superfamily Aleyrodidae. The A. spiniferus mitogenome contains 36 genes, including 13 protein-coding genes (PCGs), 21 transfer RNAs (tRNA), two ribosomal RNAs (rRNA) and a large non-coding region (control region, CR). Like most whiteflies, the A. spiniferus mitogenome had a large degree of rearrangement due to translocation of the nad3-trnG-cox3 gene cluster. The 13 PCGs initiated with ATN and generally terminated with TAA, although some used TAG or T as stop codons; atp6 showed the highest evolutionary rate, whereas cox2 appeared to have the lowest rate. The A. spiniferus mitogenome had 21 tRNAs with a typical cloverleaf secondary structure composed of four arms. Modeling of the two rRNA genes indicated that their secondary structure was similar to that of other insects. The CR of A. spiniferus was 920 bp and mapped between the nad3-trnG-cox3 and trnI-trnM gene clusters. One potential stem-loop structure and five tandem repeats were identified in the CR. Phylogenetic relationships of 11 species from the Aleyrodidae were analyzed based on the deduced amino acid sequences of the 13 PCGs and evolutionary characteristics were explored. Species with more genetic rearrangements were generally more evolved within the Aleyrodidae. PMID- 27551783 TI - Users Polarization on Facebook and Youtube. AB - Users online tend to select information that support and adhere their beliefs, and to form polarized groups sharing the same view-e.g. echo chambers. Algorithms for content promotion may favour this phenomenon, by accounting for users preferences and thus limiting the exposure to unsolicited contents. To shade light on this question, we perform a comparative study on how same contents (videos) are consumed on different online social media-i.e. Facebook and YouTube over a sample of 12M of users. Our findings show that content drives the emergence of echo chambers on both platforms. Moreover, we show that the users' commenting patterns are accurate predictors for the formation of echo-chambers. PMID- 27551786 TI - Mineralocorticoid receptor antagonists: a patent evaluation of US20150284376A1. AB - INTRODUCTION: Recent clinical studies showed that mineralocorticoid receptor antagonists are able to markedly reduce the overall and cardiovascular mortality in patients with left ventricular systolic dysfunction and mild or severe symptoms of chronic heart failure (HF). Beyond cardiac diseases, new indications of MRAs increase exponentially, especially in patients with impaired renal function. Most of the developed mineralocorticoid receptor antagonists are now non-steroidal. Identifying so-called "kidney friendly" compounds (i.e. with less renal potassium sparing properties as compared to classical steroidal MRA and therefore better safety profile in at-risk patients) would represent a clear breakthrough and many companies have developed intense patent activities in the field. AREA COVERED: The present article provides an analysis of US20150284376 patent application which discloses non-steroidal compounds. EXPERT OPINION: Of US20150284376 discloses a new class of MRA for which it is too early for determining the relevance in the absence of preclinical studies. PMID- 27551784 TI - Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors. AB - Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides. PMID- 27551785 TI - How Can the Health System Retain Women in HIV Treatment for a Lifetime? A Discrete Choice Experiment in Ethiopia and Mozambique. AB - INTRODUCTION: Option B+, an approach that involves provision of antiretroviral therapy (ART) to all HIV-infected pregnant women for life, is the preferred strategy for prevention of mother to child transmission of HIV. Lifelong retention in care is essential to its success. We conducted a discrete choice experiment in Ethiopia and Mozambique to identify health system characteristics preferred by HIV-infected women to promote continuity of care. METHODS: Women living with HIV and receiving care at hospitals in Oromia Region, Ethiopia and Zambezia Province, Mozambique were shown nine choice cards and asked to select one of two hypothetical health facilities, each with six varying characteristics related to the delivery of HIV services for long term treatment. Mixed logit models were used to estimate the influence of six health service attributes on choice of clinics. RESULTS: 2,033 women participated in the study (response rate 97.8% in Ethiopia and 94.7% in Mozambique). Among the various attributes of structure and content of lifelong ART services, the most important attributes identified in both countries were respectful provider attitude and ability to obtain non-HIV health services during HIV-related visits. Availability of counseling support services was also a driver of choice. Facility type, i.e., hospital versus health center, was substantially less important. CONCLUSIONS: Efforts to enhance retention in HIV care and treatment for pregnant women should focus on promoting respectful care by providers and integrating access to non-HIV health services in the same visit, as well as continuing to strengthen counseling. PMID- 27551796 TI - Methods in microbiome research. PMID- 27551787 TI - Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma. AB - INTRODUCTION: Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. METHODS: This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non treponemal Rapid Plasma Reagin (RPR) test. RESULTS: A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual seropositivity (p = 0.005). Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA. DISCUSSION: In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated. PMID- 27551797 TI - Response to Protocol Review Scenario: Leave the research presentations to the principal investigators. PMID- 27551798 TI - What are the limits of confidentiality for IACUC members? PMID- 27551799 TI - Response to Protocol Review Scenario: Loose lips can sink ships-and potentially careers and institutions. PMID- 27551800 TI - Response to Protocol Review Scenario: A word from USDA and OLAW. PMID- 27551801 TI - Response to Protocol Review Scenario: A matter of interpretation. PMID- 27551802 TI - The tuberculin skin test in monkeys. PMID- 27551803 TI - Passive narcosis for anesthesia induction in cotton rats (Sigmodon hispidus). AB - Cotton rats (Sigmodon hispidus) are widely used as animal models for infectious disease and immunological research. They emulate many aspects of human disease pathogenesis, and the introduction of cotton rat-specific immunological reagents, cell lines and sequencing of relevant genes have all helped to increase the popularity of this disease model. However, the use of cotton rats is problematic owing to their propensity for aggressive responses when handled, which can lead to escape, increased stress to the animals, and bites to staff. When cotton rats are co-housed, which is recommended under current social housing guidelines, these risks are increased. Here, we describe a method of isoflurane anesthesia induction in the home cage that reduces the risk of animal escape, minimizes stress during induction, and provides additional safety for staff. The method uses inexpensive materials that are widely available and can be easily disinfected. Our method also eliminates the need for expensive and cumbersome machines traditionally used with anesthetic chambers, and uses a minimal amount of inhalant anesthetic, saving resources and protecting staff from inhalation of leaked gas. PMID- 27551804 TI - Tools for organizing training, part 3. PMID- 27551805 TI - The enrichment club. PMID- 27551808 TI - Vaccine adjuvants: Why and how. AB - Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety. PMID- 27551807 TI - Defects in Stratum Corneum Desquamation Are the Predominant Effect of Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis. AB - Harlequin Ichthyosis is a severe skin disease caused by mutations in the human gene encoding ABCA12. Here, we characterize a novel mutation in intron 29 of the mouse Abca12 gene that leads to the loss of a 5' splice donor site and truncation of the Abca12 RNA transcript. Homozygous mutants of this smooth skin or smsk allele die perinatally with shiny translucent skin, typical of animal models of Harlequin Ichthyosis. Characterization of smsk mutant skin showed that the delivery of glucosylceramides and CORNEODESMOSIN was defective, while ultrastructural analysis revealed abnormal lamellar bodies and the absence of lipid lamellae in smsk epidermis. Unexpectedly, mutant stratum corneum remained intact when subjected to harsh chemical dissociation procedures. Moreover, both KALLIKREIN 5 and -7 were drastically decreased, with retention of desmoplakin in mutant SC. In cultured wild type keratinocytes, both KALLIKREIN 5 and -7 colocalized with ceramide metabolites following calcium-induced differentiation. Reducing the intracellular levels of glucosylceramide with a glucosylceramide synthase inhibitor resulted in decreased secretion of KALLIKREIN proteases by wild type keratinocytes, but not by smsk mutant keratinocytes. Together, these findings suggest an essential role for ABCA12 in transferring not only lipids, which are required for the formation of multilamellar structures in the stratum corneum, but also proteolytic enzymes that are required for normal desquamation. Smsk mutant mice recapitulate many of the pathological features of HI and can be used to explore novel topical therapies against a potentially lethal and debilitating neonatal disease. PMID- 27551809 TI - Genome sequencing identifies a non-coding variant in the MCDR1 locus as a cause of macular dystrophy. PMID- 27551810 TI - A Macroscopic Model for Simulating the Mucociliary Clearance in a Bronchial Bifurcation: The Role of Surface Tension. AB - The mucociliary clearance in the bronchial tree is the main mechanism by which the lungs clear themselves of deposited particulate matter. In this work, a macroscopic model of the clearance mechanism is proposed. Lubrication theory is applied for thin films with both surface tension effects and a moving wall boundary. The flow field is computed by the use of a finite-volume scheme on an unstructured grid that replicates a bronchial bifurcation. The carina in bronchial bifurcations is of special interest because it is a location of increased deposition of inhaled particles. In this study, the mucus flow is computed for different values of the surface tension. It is found that a minimal surface tension is necessary for efficiently removing the mucus while maintaining the mucus film thickness at physiological levels. PMID- 27551811 TI - Nanoporous Silver Film Fabricated by Oxygen Plasma: A Facile Approach for SERS Substrates. AB - Nanoporous metal films are promising substrates for surfaced-enhanced Raman scattering (SERS) measurement, owing to their homogeneity, large surface area, and abundant hot-spots. Herein, a facile procedure was developed to fabricate nanoporous Ag film on various substrate surfaces. Thermally deposited Ag film was first treated with O2 plasma, resulting in porous Ag/AgxO film (AgxO-NF) with nanoscale feature. Sodium citrate was then used to reduce AgxO to Ag, forming nanoporous Ag film (AgNF) with similar morphology. The AgNF substrate demonstrates 30-fold higher Raman intensity than Ag film over polystyrene nanospheres (d = 600 nm) using 4-mercaptobenzoic acid (4-MBA) as the sensing molecule. Comparing with ordinary Raman measurement on 4-MBA solution, an enhancement factor of ~6 * 10(6) was determined for AgNF. The AgNF substrate was evaluated for benzoic acid, 4-nitrophenol, and 2-mercaptoethanesulfonate, showing high SERS sensitivity for chemicals that bind weakly to Ag surface and molecules with relatively small Raman cross section at micromolar concentration. In addition to its simplicity, the procedure can be applied to various materials such as transparency film, filter paper, hard polystyrene film, and aluminum foil, revealing similar Raman sensitivity. By testing the durability of the substrate, we found that the AgxO films can be stored in ambient conditions for more than 90 days and still deliver the same SERS intensity if the films are treated with sodium citrate before use. These results demonstrate the advantage of the proposed approach for mass production of low-cost, sensitive, and durable SERS substrates. The transferable nature of these AgNF to different flexible surfaces also allows their easy integration with other sensing schemes. PMID- 27551812 TI - Pediatric Palliative Care and Child Psychiatry: A Model for Enhancing Practice and Collaboration. AB - As the field of Pediatric Palliative Care continues to develop, it is important to consider the scope of practice and the utility of collaboration with other specialties, including child and adolescent psychiatry. The integration of psychiatry and palliative medicine has been explored in adult practice, but has not yet been elaborated in pediatrics. This article proposes a clinical model of care that highlights the overlapping and unique expertise that each discipline brings, in a continuum of collaboration, and proposes an integrated care model for the most complex patients and families. Case examples are used to define specific professional skills and roles, and to describe shared and distinct clinical approaches used by pediatric palliative care and child psychiatry. Effective collaboration provides opportunities for cross-disciplinary educational exchange and enhanced care of children and families with comorbid mental health issues and serious illness. PMID- 27551813 TI - Implications of trauma and subsequent articulation on the release of Proteoglycan 4 and tissue response in adult human ankle cartilage. AB - The purpose of this study was to investigate the effects of trauma and subsequent articulation on adult human ankle cartilage subjected to an injurious impact. Trauma was initiated through impaction on talar cartilage explants. Articulation and loading were applied in a joint bioreactor over 5 consecutive days. The early (24 h) effects of impaction included a reduced chondrocytes viability (51% vs. 81% for non-impacted; p = 0.03), increased levels of apoptosis (43% vs. 27%; p = 0.03), and an increase in the histopathology score (4.4 vs. 1.7; p = 0.02) as compared to non-impacted cartilage explants. One of the key findings was that damage also stimulated the PRG4 release (2.2 vs. 1.5 MUg/ml). Subsequent articulation for 5 days did not lead to further changes in tissue histopathology and cell viability, neither for injured nor non-injured samples. However, articulation led to an increased apoptosis in the injured samples (p = 0.03 for the interaction term). Articulation also caused a significant increase of PG/GAG release into the culture medium (p = 0.04) for both injured and non-injured samples; however, the synthesis of PG was not affected by articulation (p = 0.45) though the PG synthesis was higher in injured samples (p < 0.01). With regard to the PRG4 release, impacted samples continued to show higher amounts (p = 0.01), adding articulation led to a reduction (p = 0.02). The current study demonstrated that adult human talar cartilage increases both the PRG4 release and biosynthetic activity as an immediate cellular response to injury. Articulation played a less contributing role to biosynthesis and remodeling, behaving mostly neutral, in that no further damage emerged. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:667-676, 2017. PMID- 27551815 TI - Recent research progress on preparation and application of N, N, N-trimethyl chitosan. AB - N,N,N-trimethyl chitosan (TMC) is a quaternized chitosan derivative with excellent solubility in aqueous solutions. It has been extensively studied as an absorption enhancer, antibacterial agent and gene vector due to its ability to form complexes with anionic gels or macromoleculars. However, the research which describes the process of TMC preparation and its new applications has not been fully reviewed. In this paper, recent progress regarding different TMC preparation methods and its characterization and application in different fields is presented. Key findings are compared and summarized and some topics for further study are suggested. PMID- 27551814 TI - Ultrashort Echo-Time Magnetic Resonance Imaging Is a Sensitive Method for the Evaluation of Early Cystic Fibrosis Lung Disease. AB - RATIONALE: Recent advancements that have been made in magnetic resonance imaging (MRI) improve our ability to assess pulmonary structure and function in patients with cystic fibrosis (CF). A nonionizing imaging modality that can be used as a serial monitoring tool throughout life can positively affect patient care and outcomes. OBJECTIVES: To compare an ultrashort echo-time MRI method with computed tomography (CT) as a biomarker of lung structure abnormalities in young children with early CF lung disease. METHODS: Eleven patients with CF (mean age, 31.8 +/- 5.7 mo; median age, 33 mo; 7 male and 4 female) were imaged via CT and ultrashort echo-time MRI. Eleven healthy age-matched patients (mean age, 22.5 +/- 10.2 mo; median age, 23 mo; 5 male and 6 female) were imaged via ultrashort echo-time MRI. CT scans of 13 additional patients obtained for clinical indications not affecting the heart or lungs and interpreted as normal provided a CT control group (mean age, 24.1 +/- 11.7 mo; median age, 24 mo; 6 male and 7 female). Studies were scored by two experienced radiologists using a well-validated CF specific scoring system for CF lung disease. MEASUREMENTS AND MAIN RESULTS: Correlations between CT and ultrashort echo-time MRI scores of patients with CF were very strong, with P values <=0.001 for bronchiectasis (r = 0.96) and overall score (r = 0.90), and moderately strong for bronchial wall thickening (r = 0.62, P = 0.043). MRI easily differentiated CF and control groups via a reader CF specific scoring system. CONCLUSIONS: Ultrashort echo-time MRI detected structural lung disease in very young patients with CF and provided imaging data that correlated well with CT. By quantifying early CF lung disease without using ionizing radiation, ultrashort echo-time MRI appears well suited for pediatric patients requiring longitudinal imaging for clinical care or research studies. Clinical Trial registered with www.clinicaltrials.gov (NCT01832519). PMID- 27551817 TI - Progressing Preemptive Genotyping of CYP2C19 Allelic Variants for Sickle Cell Disease Patients. AB - AIMS: Interindividual variability in drug response and adverse effects have been described for proton pump inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, tricyclic antidepressants, and anti-infectives, but little is known about the safety and efficacy of these medications in patients with sickle cell disease (SCD). We genotyped the CYP2C19 gene which has been implicated in the metabolism of these drugs in an SCD patient cohort to determine the frequencies of reduced function, increased function, or complete loss-of function variants. MATERIALS AND METHODS: DNAs from 165 unrelated SCD patients were genotyped for nine CYP2C19 (*2, *3, *4, *5, *6, *7,*8, *12, and *17) alleles using the iPLEX(r) ADME PGx multiplex panel. RESULTS: Three CYP2C19 alleles (*2, *12, and *17) were detected with the following frequencies: 0.209, 0.006, and 0.236, respectively. The predicted phenotype frequencies were distributed as extensive (31.5%), intermediate (24.8%), poor (5.5%), ultrarapid (30.3%), and unknown metabolizers (7.9%). DISCUSSION: Prognostic genotyping is potentially useful for identifying SCD patients with allelic variants linked to proven clinical pharmacokinetic consequences for several drugs metabolized by the CYP2C19 gene. However, the main challenge to implementing a genetics-guided prescribing practice is ensuring concordance between CYP2C19 genotypes and metabolic phenotypes in SCD patients. PMID- 27551816 TI - Determining If Sex Bias Exists in Human Surgical Clinical Research. AB - Importance: Sex is a variable that is poorly controlled for in clinical research. Objectives: To determine if sex bias exists in human surgical clinical research, to determine if data are reported and analyzed using sex as an independent variable, and to identify specialties in which the greatest and least sex biases exist. Design, Setting, and Participants: For this bibliometric analysis, data were abstracted from 1303 original peer-reviewed articles published from January 1, 2011, through December 31, 2012, in 5 surgery journals. Main Outcomes and Measures: Study type, location, number and sex of participants, degree of sex matching of included participants, and inclusion of sex-based reporting, statistical analysis, and discussion of data. Results: Of 2347 articles reviewed, 1668 (71.1%) included human participants. After excluding 365 articles, 1303 remained: 17 (1.3%) included males only, 41 (3.1%) included females only, 1020 (78.3%) included males and females, and 225 (17.3%) did not document the sex of the participants. Although female participants represent more than 50% (n = 57 688 606) of the total number (115 377 213) included, considerable variability existed with the number of male (46 111 818), female (58 805 665), and unspecified (10 459 730) participants included among the journals, between US domestic and international studies, and between single vs multicenter studies. For articles included in the study, 38.1% (497 of 1303) reported these data by sex, 33.2% (432 of 1303) analyzed these data by sex, and 22.9% (299 of 1303) included a discussion of sex-based results. Sex matching of the included participants in the research overall was poor, with 45.2% (589 of 1303) of the studies matching the inclusion of both sexes by 50%. During analysis of the different surgical specialties, a wide variation in sex-based inclusion, matching, and data reporting existed, with colorectal surgery having the best matching of male and female participants and cardiac surgery having the worst. Conclusions and Relevance: Sex bias exists in human surgical clinical research. Few studies included men and women equally, less than one-third performed data analysis by sex, and there was wide variation in inclusion and matching of the sexes among the specialties and the journals reviewed. Because clinical research is the foundation for evidence-based medicine, it is imperative that this disparity be addressed so that therapies benefit both sexes. PMID- 27551819 TI - Conscientiousness and Extraversion relate to responsiveness to tempo in dance. AB - Previous research has shown broad relationships between personality and dance, but the relationship between personality and specific structural features of music has not been explored. The current study explores the influence of personality and trait empathy on dancers' responsiveness to small tempo differences between otherwise musically identical stimuli, measured by difference in the amount in acceleration of key joints. Thirty participants were recorded using motion capture while dancing to excerpts from six popular songs that were time-stretched to be slightly faster or slower than their original tempi. Analysis revealed that higher conscientiousness and lower extraversion both correlated with greater responsiveness to tempo change. Partial correlation analysis revealed that conscientiousness remained significantly correlated with responsiveness when extraversion was controlled, but not vice versa. No effect of empathy was found. Implications are discussed. PMID- 27551818 TI - Investigation of factors impacting mobility and gait in Parkinson disease. AB - Mobility and gait limitations are major issues for people with Parkinson disease (PD). Identification of factors that contribute to these impairments may inform treatment and intervention strategies. In this study we investigated factors that predict mobility and gait impairment in PD. Participants with mild to moderate PD and without dementia (n=114) were tested in one session 'off' medication. Mobility measures included the 6-Minute Walk test and Timed-Up-and-Go. Gait velocity was collected in four conditions: forward preferred speed, forward dual task, forward fast as possible and backward walking. The predictors analyzed were age, gender, disease severity, balance, balance confidence, fall history, self reported physical activity, and executive function. Multiple regression models were used to assess the relationships between predictors and outcomes. The predictors, in different combinations for each outcome measure, explained 55.7% to 66.9% of variability for mobility and 39.5% to 52.8% for gait velocity. Balance was the most relevant factor (explaining up to 54.1% of variance in mobility and up to 45.6% in gait velocity). Balance confidence contributed to a lesser extent (2.0% to 8.2% of variance) in all models. Age explained a small percentage of variance in mobility and gait velocity (up to 2.9%). Executive function explained 3.0% of variance during forward walking only. The strong predictive relationships between balance deficits and mobility and gait impairment suggest targeting balance deficits may be particularly important for improving mobility and gait in people with PD, regardless of an individual's age, disease severity, fall history, or other demographic features. PMID- 27551820 TI - The effects of autonomous difficulty selection on engagement, motivation, and learning in a motion-controlled video game task. AB - This experiment investigated the relationship between motivation, engagement, and learning in a video game task. Previous studies have shown increased autonomy during practice leads to superior retention of motor skills, but it is not clear why this benefit occurs. Some studies suggest this benefit arises from increased motivation during practice; others suggest the benefit arises from better information processing. Sixty novice participants were randomly assigned to a self-controlled group, who chose the progression of difficulty during practice, or to a yoked group, who experienced the same difficulty progression but did not have choice. At the end of practice, participants completed surveys measuring intrinsic motivation and engagement. One week later, participants returned for a series of retention tests at three different difficulty levels. RM-ANCOVA (controlling for pre-test) showed that the self-controlled group had improved retention compared to the yoked group, on average, beta=46.78, 95% CI=[2.68, 90.87], p=0.04, but this difference was only statistically significant on the moderate difficulty post-test (p=0.004). The self-controlled group also showed greater intrinsic motivation during practice, t(58)=2.61, p=0.01. However, there was no evidence that individual differences in engagement (p=0.20) or motivation (p=0.87) were associated with learning, which was the relationship this experiment was powered to detect. These data are inconsistent with strictly motivational accounts of how autonomy benefits learning, instead suggesting the benefits of autonomy may be mediated through other mechanisms. For instance, within the information processing framework, the learning benefits may emerge from learners appropriately adjusting difficulty to maintain an appropriate level of challenge (i.e., maintaining the relationship between task demands and cognitive resources). PMID- 27551821 TI - Reconciling the evolutionary origin of bread wheat (Triticum aestivum). AB - The origin of bread wheat (Triticum aestivum; AABBDD) has been a subject of controversy and of intense debate in the scientific community over the last few decades. In 2015, three articles published in New Phytologist discussed the origin of hexaploid bread wheat (AABBDD) from the diploid progenitors Triticum urartu (AA), a relative of Aegilops speltoides (BB) and Triticum tauschii (DD). Access to new genomic resources since 2013 has offered the opportunity to gain novel insights into the paleohistory of modern bread wheat, allowing characterization of its origin from its diploid progenitors at unprecedented resolution. We propose a reconciled evolutionary scenario for the modern bread wheat genome based on the complementary investigation of transposable element and mutation dynamics between diploid, tetraploid and hexaploid wheat. In this scenario, the structural asymmetry observed between the A, B and D subgenomes in hexaploid bread wheat derives from the cumulative effect of diploid progenitor divergence, the hybrid origin of the D subgenome, and subgenome partitioning following the polyploidization events. PMID- 27551822 TI - Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail. AB - Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals' genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals' genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID- 27551823 TI - Large-Scale Recombinant Expression and Purification of Human Tyrosinase Suitable for Structural Studies. AB - Human tyrosinase (TYR) is a glycoprotein that initiates the first two reactions in the melanin biosynthesis pathway. Mutations in its encoding gene cause Oculocutaneous Albinism type I (OCA1), the most severe form of albinism, which is a group of autosomal recessive disorders characterized by reduced or absent production of melanin in skin, hair and eyes. Despite extensive structural and characterization studies of its homologues in lower eukaryotic organisms, the catalytic mechanism of human TYR and the molecular basis of OCA1 are largely unknown. In this work, we have carried out a large-scale recombinant expression of TYR that has enabled us to obtain high yields of pure and active protein, required for crystallization trials and screening of skin whitening agents, which is highly demanded in the cosmetic industry. Addition of an N-terminal honeybee melittin signal peptide for secretion of the produced protein into the (protein free) medium, as well as a cleavable His-tag at the C-terminus, was crucial for increasing the yield of pure protein. We have successfully crystallized two TYR variants, in both glycosylated and deglycosylated forms, showing preliminary X ray diffraction patterns at 3.5 A resolution. Hence, we have established an expression and purification protocol suitable for the crystal structure determination of human TYR, which will give unique atomic insight into the nature and conformation of the residues that shape the substrate binding pocket that will ultimately lead to efficient compound design. PMID- 27551825 TI - "I can sit on the beach and punt through my mobile phone": The influence of physical and online environments on the gambling risk behaviours of young men. AB - Gambling is rapidly emerging as an important public health issue, with gambling products causing considerable health and social harms to individuals, families and communities. Whilst researchers have raised concerns about online wagering environments, few studies have sought to explore how factors within different gambling environments (both online and land-based) may be influencing the wagering, and more broadly the gambling risk behaviours of young men. Using semi structured interviews with 50 Australian men (20-37 years) who gambled on sport, we explored the ways in which online and land-based environments may be risk promoting settings for gambling. This included the appeal factors associated with gambling in these environments, factors that encouraged individuals to gamble, and factors that encouraged individuals to engage in different, and more harmful types of gambling. Interviews were conducted over the course of a year (April 2015 - April 2016). We identified a number of situational and structural factors that promoted risky gambling environments for young men. In the online environment, gambling products had become exceedingly easy to access through mobile technologies, with young men subscribing to multiple accounts to access industry promotions. The intangibility of money within online environments impacted upon risk perceptions. In land-based environments, the social rituals associated with peer group behaviour and sport influenced risky patterns of gambling. The presence of both gambling and alcohol in pub environments led individuals to gamble more than they normally would, and on products that they would not normally gamble on. Land-based venues also facilitated access to multiple forms of gambling under the one roof. We identified a number of factors in both land and online environments that when combined, created risk-promoting settings for gambling among young men. By exploring these contextual conditions that give rise to gambling harm, we are better able to advocate for effective public health responses in creating environments that prevent harmful gambling. PMID- 27551824 TI - Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task. AB - Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a "Stop" process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception. PMID- 27551826 TI - Interventions to improve child-parent-medical provider communication: A systematic review. AB - RATIONALE: Research related to effective communication between children/parents and medical providers is limited. OBJECTIVE: To review interventions seeking to improve communication between children/parents and medical providers. METHODS: The inclusion criteria were interventions in peer-reviewed articles and dissertations in English. Because of the limited availability of pediatric communication research, no restrictions were placed on the year, design, and length of follow-up of the interventions. Out of 4163 articles in the CINAHL, Cochrane, EMBASE, ERIC, MEDLINE, and PsycINFO databases, 34 met the inclusion criteria. The design, strategies, measurement tools, results, and conflicts of interest of the interventions were reviewed. RESULTS: Most interventions were conducted in the United States, had a small sample size, and used a pre-posttest design. Fifteen were randomized controlled trials (RCTs). The most frequent intervention strategies were role-playing sessions and seminars for medical providers. Standardized children (i.e., fictitious child patients) were frequently used to help train physicians. Most interventions improved providers' interpersonal, patient-centered interviewing skills. Interventions that targeted parents involved booklets and role-playing to encourage questions. They improved parents' satisfaction and communication. An intervention that targeted youth used a video portraying how children can communicate better with physicians. Once the children aged 5-15 years watched the video, they wrote questions for their physicians prior to the medical visit. The experimental group of children had better rapport with physicians and could recall recommendations about medications more often than the control group. CONCLUSION: More RCTs involving children as active participants are needed. PMID- 27551827 TI - Breastfeeding duration and offspring conduct problems: The moderating role of genetic risk. AB - RATIONALE: A sizable body of research has examined associations between breastfeeding and various facets of offspring development, including childhood behavioral problems. Notwithstanding the number of studies on the topic, breastfeeding has not consistently been linked to child misbehaviors. Moreover, empirical examinations of whether breastfeeding is differentially predictive of conduct problems among individuals with varying degrees of genetic risk are lacking. OBJECTIVE: The present study examines whether a short duration of breastfeeding and genetic risk interact to predict conduct problems during childhood. METHODS: A genetically informative design is employed to examine a subsample of twins from the Early Childhood Longitudinal Study: Birth Cohort (ECLS-B), a nationally representative sample of American children. RESULTS: The findings suggest that a shorter duration of breastfeeding only enhances the risk of offspring conduct problems among children who possess high levels of genetic risk. Conversely, longer breastfeeding durations were found to protect against childhood behavioral problems when genetic risk was high. CONCLUSIONS: Indicators of genetic risk may help to distinguish individuals whose behavioral development is most sensitive to the duration of breastfeeding. Future research should seek to replicate and extend these findings by considering genetic factors as potential markers of differential susceptibility to breastfeeding duration. PMID- 27551828 TI - Low Heart Rate Variability in a 2-Minute Electrocardiogram Recording Is Associated with an Increased Risk of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities Study. AB - Low heart rate variability (HRV) has been linked to increased total mortality in the general population; however, the relationship between low HRV and sudden cardiac death (SCD) is less well-characterized. The goal of this study was to evaluate the relationship between low HRV and SCD in a community-based cohort. Our cohort consisted of 12,543 participants from the Atherosclerosis Risk in Communities (ARIC) study. HRV measures were derived from 2-minute electrocardiogram recordings obtained during the baseline exam (1987-89). Time domain measurements included the standard deviation of all normal RR intervals (SDNN) and the root mean squared successive difference (r-MSSD). Frequency domain measurements included low frequency power (LF) and high frequency (HF) power. During a median follow-up of 13 years, 215 SCDs were identified from physician adjudication of all coronary heart disease deaths through 2001. In multivariable adjusted Cox proportional hazards models, each standard deviation decrement in SDNN, LF, and HF were associated with 24%, 27% and 16% increase in SCD risk, respectively. Low HRV is independently associated with increased risk of SCD in the general population. PMID- 27551829 TI - A Hybrid Short-Term Traffic Flow Prediction Model Based on Singular Spectrum Analysis and Kernel Extreme Learning Machine. AB - Short-term traffic flow prediction is one of the most important issues in the field of intelligent transport system (ITS). Because of the uncertainty and nonlinearity, short-term traffic flow prediction is a challenging task. In order to improve the accuracy of short-time traffic flow prediction, a hybrid model (SSA-KELM) is proposed based on singular spectrum analysis (SSA) and kernel extreme learning machine (KELM). SSA is used to filter out the noise of traffic flow time series. Then, the filtered traffic flow data is used to train KELM model, the optimal input form of the proposed model is determined by phase space reconstruction, and parameters of the model are optimized by gravitational search algorithm (GSA). Finally, case validation is carried out using the measured data of an expressway in Xiamen, China. And the SSA-KELM model is compared with several well-known prediction models, including support vector machine, extreme learning machine, and single KLEM model. The experimental results demonstrate that performance of the proposed model is superior to that of the comparison models. Apart from accuracy improvement, the proposed model is more robust. PMID- 27551832 TI - Endobutton Fixation Technique for Multifragmented Coronoid Fractures. AB - Coronoid fractures commonly occur in a part of unstable elbow fractures. Stable coronoid fracture fixation is important for early elbow motion. It may be difficult to fix multifragmented coronoid process fractures with loose capsular attachment. Thus, we demonstrated the endobutton suspensory technique to fix the anterior coronoidal fragments due to its suspensory effect providing capsular attachment. This technique allows stable fixation to the small multifragmented coronoid fractures with early range of motion. PMID- 27551830 TI - Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves. AB - Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID- 27551831 TI - Contrast Circulation Time to Assess Right Ventricular Dysfunction in Pulmonary Embolism: A Retrospective Pilot Study. AB - OBJECTIVE: To optimize enhancement of pulmonary arteries and facilitate diagnosis of pulmonary embolism (PE), modern computed tomography angiography (CTA) contains a contrast bolus tracking system. We explored the diagnostic accuracy of the time intensity curves given by this automated system to identify right ventricular dysfunction (RVD) in acute PE. METHODS: 114 CTAs with a diagnosis of PE were reviewed. RVD was defined as right-to-left ventricular diameter ratio of 1 or greater. Four parameters on time-intensity curves were identified. Parameters between CTAs with and those without RVD were compared with the Wilcoxon rank-sum test. The ability of the four parameters to discriminate patients with RVD was explored by compiling the area under the operating curves (AUC). RESULTS: The time needed by the contrast media to reach the pulmonary artery [8 seconds (IQR: 7-9) versus 7 seconds (IQR: 6-8), p<0.01], the time needed to reach 40 Hounsfield units (HU) [11 seconds (IQR: 8.5-14) versus 9.5 seconds (IQR: 8-10.5), p<0.01], and the contrast intensity reached after 10 seconds [19 HU (IQR: 4-67) versus 53 HU (IQR: 32-80), p<0.05] were all statistically different between CTA with and CTA without RVD. Those three parameters changed gradually across severity categories of RVD (p<0.05 for trend). Their AUC to identify RVD ranged from 0.63 to 0.66. The slope of contrast intensity over time was not informative: [31 HU/s (IQR: 20-57) in CTA with, compared to 36 HU/s (IQR: 22.5-53) in CTA without RVD, p = 0.60]. CONCLUSION: Several parameters of the time-intensity curve obtained by the bolus tracking system are associated with RVD assessed on CTA images. Of those, the time needed to reach a predefined threshold seems to be the easiest to obtain in any CTA without additional processing time or contrast injection. However, the performance of those parameters is globally low. PMID- 27551833 TI - Flavonoids and Naphthoflavonoids: Wider Roles in the Modulation of Cytochrome P450 Family 1 Enzymes. AB - The human cytochrome P450 family 1 enzymes consist of three members, CYP1A1, CYP1A2 and CYP1B1, which are predominantly involved in the phase I metabolism of xenobiotics. Because they have been implicated in carcinogenesis, cancer progression, and drug resistance, the inhibition of these enzymes has been widely considered an effective oncological therapeutic strategy. Some natural and synthetic flavonoids and naphthoflavonoids have been extensively documented to exert pronounced influence in the modulation of CYP1s, including functioning as inhibitors, substrates, and aryl hydrocarbon receptor (AhR) ligands. However, the molecular determinants behind these effects are still unknown. This review summarizes the structural features responsible for the CYP1 inhibitory effects of the reported flavonoids and naphthoflavonoids. Additionally, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed to better understand the effect of their structural properties on biological activities. We hope this review provides a useful foundation for the rational design of potent and selective CYP1 isozyme inhibitors, thereby accelerating the drug discovery process. PMID- 27551834 TI - Genetic variation of MMP-2(-735 C>T) and MMP-9(-1562 C>T) gene in risk of development of HAND and severity of HAND. AB - BACKGROUND: Astrocytes are susceptible to HIV-1 infection. Neurocognitive dysfunction has also been associated with the toxicity of certain antiretroviral drugs. HIV-1 induced neurological toxicity has been associated with deficiency of matrix metalloproteinases. Therefore, we evaluated the association of MMP-2(-735C > T) and MMP-9(-1562C > T) polymorphisms with respect to the susceptibility of developing HIV-associated neurocognitive disorders (HAND) and its severity. METHODS: We enrolled 50 HIV-infected individuals with HAND, 130 without HAND and 150 unrelated healthy controls. Polymorphism for MMP-2-735C > T and MMP-9-1562C > T genes was genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Individuals with the MMP-2 -735 CT genotype and -735 T allele were at higher risk of developing HAND [odds ratio (OR) = 5.27, 95% confidence interval (CI) = 1.30-21.35, p = 0.02 and OR = 2.27, 95% CI = 1.57 3.27, p = 0.0001 respectively]. The MMP-2 -735 CT genotype and -735 T allele of MMP-2 were associated with a reduced likelihood of severe HAND (OR =0.32, 95% CI = 0.15-0.66, p = 0.002 and OR = 0.32, 95% CI = 0.14-0.71, p = 0.005). When evaluating gene-gene interaction models, the combined genotype MMP-2-735TT + MMP 9-1562CC and MMP-2-735CT + MMP-9-1562CT was associated with the risk of developing HAND (OR = 4.84, p = 0.0001, OR = 1.81, p = 0.03). However, individuals with the combined genotype of MMP-2-735TT + MMP-9-1562CC were found to be protective for severe HAND (OR = 0.30, 95% CI = 0.13-0.67, p = 0.003). CONCLUSIONS: Individuals with the MMP-2 -735CT genotype, -735 T allele and combined genotype MMP-2 -735TT + MMP-9 -1562CC had an enhanced risk of developing HAND. Those with the MMP-2 -735 CT genotype, -735 T allele and combined genotype of MMP-2-735TT + MMP-9-1562CC were suggested to have protection from developing severe HAND. PMID- 27551835 TI - Radiolabeled choline PET/CT before salvage lymphadenectomy dissection: a systematic review and meta-analysis. AB - To provide a systematic review of recently published reports and carry out a meta analysis on the use of radiolabeled choline PET/computed tomography (CT) as a guide for salvage lymph node dissection (sLND) in prostate cancer patients with biochemical recurrence after primary treatments. Bibliographic database searches, from 2005 to May 2015, including Pubmed, Web of Science, and TripDatabase, were performed to find studies that included only patients who underwent sLND after radiolabeled choline PET/CT alone or in combination with other imaging modalities. For the qualitative assessment, all studies including the selected population were considered. Conversely, for the quantitative assessment, articles were included only if absolute numbers of true positive, true negative, false positive, and false negative test results were available or derivable from the text for lymph node metastases. Reviews, clinical reports, and editorial articles were excluded from analyses. Eighteen studies fulfilled the inclusion criteria and were assessed qualitatively. A total of 750 patients underwent radiolabeled choline (such as C-choline or F-choline) PET/CT before sLND. A quantitative evaluation was performed in nine studies. A patient-based, a lesion-based, and a site-based analysis was carried out in nine, four, and five studies, respectively. The pooled sensitivities were 85.3% [95% confidence interval (CI): 78.5-90.3%], 56.2% (95% CI: 41.6-69.7%), 75.3% (95% CI: 56.6-87.7%), and 63.7% (95% CI: 41-81.6%), respectively, for patient-based, lesion-based, pelvic site based, and retroperitoneal site-based analysis. The pooled positive predictive values (PPVs) were 75% (95% CI: 68-80.9%), 85.8% (95% CI: 66.8-94.8%), 81.2% (95% CI: 70.1-88.9%), and 75.2% (95% CI: 58.7-86.7%), respectively, in the same analyses. High heterogeneities among the studies were found for sensitivities and PPVs ranging between 61.7-93.3% and 60.6-94.5%, respectively. Radiolabeled choline PET/CT has only a moderate sensitivity for the detection of metastatic lymph nodes in patients who are candidates for sLND, although the pooled PPVs ranged between 75 and 85.8% for all type of subanalyses. The presence of high heterogeneity among the studies should be considered carefully. PMID- 27551836 TI - Data Scientists: They know what we don't know that we don't know about Big Data. PMID- 27551837 TI - Surgical management of a high jugular bulb. PMID- 27551839 TI - Erratum. PMID- 27551838 TI - Balloon dilation of the sphenoid sinus ostium for recurrent sphenoid sinusitis. PMID- 27551840 TI - Vocal fold granulomas. PMID- 27551841 TI - Hypopharyngeal strictures and webs. PMID- 27551842 TI - Are routine preoperative CT scans necessary in adult cochlear implantation? Implications for the allocation of resources in cochlear implant programs. AB - Our aim was to critically assess the influence of preoperative computed tomography (CT) scans on implantation decisions for adult cochlear implant candidates. The working hypothesis was that these routine scans might not provide critical additional information in most adult cochlear implant candidates. The charts of 175 adults with unilateral cochlear implantation were reviewed. Preoperative CT scan reports were audited, and scans with reported pathology were examined by an Otologist/ENT Surgeon. Clinic notes and multidisciplinary team meeting summaries were also analyzed to assess whether the results of the radiology report had influenced the decision to implant or the laterality of implantation. Twenty-five of the 175 scans (14.3%) showed an abnormality. Five of those 25 scans showed evidence of previous surgeries already known to the clinicians. Of the remaining 20 scans, 17 showed abnormalities, including wide vestibular aqueducts, Mondini deformities, and varying degrees of otospongiosis, the identification of which can be considered preoperatively helpful. Of the 175 scans, 3 (1.7%) demonstrated abnormalities that influenced the side of implantation or the decision to implant and, therefore, had an impact on treatment. We conclude that a preoperative CT scan seems to have an impact on treatment in only a small percentage of adult cochlear implantees. Hence, it may only need to be performed in patients with a history or clinical suspicion of meningitis or otosclerosis, if the individual was born deaf or became deaf before the age of 16, or if there are other clinical reasons to scan (e.g., otoscopic appearance). The related resources can be allocated to other facets of cochlear implant programs. PMID- 27551843 TI - Functional and psychological impact of nasal bone fractures sustained during sports activities: A survey of 87 patients. AB - Nasal bone fractures that require reduction are a common sequela of sports injuries. We conducted a survey to ascertain the outcomes of patients who had experienced a nasal bone fracture and who subsequently underwent manipulation under anesthesia. We reviewed data on 217 nasal bone fractures that had been seen at our institution over a 3-year period. Of these, 133 (61.3%) had occurred as a result of a sports activity. Thirty of the 133 patients (22.6%) had been managed conservatively, while the other 103 (77.4%) had undergone manipulation under anesthesia. We were able to contact 87 of the 103 patients (84.5%) by telephone, who served as the study population. The most common sports associated with these 87 injuries were hurling (n = 26; 29.9%), rugby (n = 22; 25.3%), Gaelic football (n = 20; 23.0%), and soccer (n = 13; 14.9%). Patients who had undergone treatment within 2 weeks were significantly more satisfied with their outcome than were those who had been treated later (p < 0.01). Twenty-six patients (29.9%) reported that their injury had had a detrimental impact on their subsequent performance in their sport; 12 (13.8%) described a fear of reinjury when they returned to play, 7 (8.0%) experienced functional problems, 3 (3.4%) complained of diminished performance, and 4 others (4.6%) quit playing contact sports altogether. To the best of our knowledge, our study is the first to demonstrate that a fracture of the nasal bones may have a notable psychological impact on an athlete and that it can lead to diminished performance or a complete withdrawal from contact sports. PMID- 27551844 TI - A case of radiation-induced mucosal melanoma in an immunohistochemically S-100 negative patient. AB - We report a case of radiation-induced mucosal melanoma in a 41-year-old woman with a history of childhood rhabdomyosarcoma of the nasal cavity that had been treated with radiotherapy. During the workup for the melanoma, the patient was found to be negative for S-100 protein on immunostaining. While many melanotic markers for the histologic confirmation of melanoma exist, they can be negative in some cases, such as ours. To the best of our knowledge, only 1 case of radiation-induced melanoma has been previously reported in the English-language literature, and in that case the patient was S-100-positive. Although our case is rare, it suggests another possible long-term adverse effect of radiotherapy. We also describe the morphologies and histology associated with diagnosing melanoma in an S-100-negative patient. PMID- 27551845 TI - Subjective and objective parameters in the evaluation of radiofrequency ablation of the inferior turbinate do not correlate: A pilot study. AB - Inferior turbinate hypertrophy is a common cause of nasal obstruction. We conducted a prospective study to correlate subjective and objective parameters in assessing the effectiveness of radiofrequency ablation (RFA). Our initial study population was made up of 10 patients who presented with nasal obstruction; 1 patient was lost to follow-up, leaving us with 7 women and 2 men, aged 26 to 65 years (mean: 37.9 +/- 12.8), and 16 turbinates (7 bilateral, 1 right, and 1 left). Visual analogue scale (VAS) scores, Nasal Obstruction and Symptom Evaluation (NOSE) questionnaire scores, rhinomanometry results, and CT- and MRI based volumetry were obtained before RFA and 6 months afterward. For the subjective parameters, the mean pre- and postoperative VAS scores for the 16 turbinates were 6.6 +/- 1.6 and 2.8 +/- 2.0 (p < 0.001), respectively, and the mean pre- and postoperative NOSE scores in the 9 patients were 15.3 +/- 3.1 and 5.8 +/- 5.4 (p = 0.003). For the objective parameters, the mean pre- and postoperative rhinomanometry values at 150 Pa were 241.0 +/- 141.3 and 265.4 +/- 157.3 ml/sec (p = 0.403), and the mean pre- and postoperative volumetry values were 5.3 +/- 2.5 and 5.0 +/- 2.1 cm(3) (p = 0.551). Note that only the differences in the subjective parameters reached statistical significance. RFA of the inferior turbinates as a treatment for nasal obstruction is safe and easy. However, our study found a discrepancy between the subjective and objective outcomes parameters, as the former showed highly significant improvement and the latter showed only a slight improvement that did not reach statistical significance. PMID- 27551846 TI - Mulberry hypertrophy and accompanying sinonasal pathologies: A review of 68 cases. AB - Mulberry hypertrophy occasionally coexists with sinonasal pathologies. There are very few reports in the literature on this clinical entity. We conducted a retrospective study to draw attention to this condition in the context of accompanying sinonasal pathologies. Our study group was made up of 68 patients-51 males and 17 females, aged 13 to 57 years (mean: 34.9)-who had been diagnosed with mulberry hypertrophy and at least one accompanying sinonasal pathology. All patients had a long-standing chronic discharge. Forty-nine of these patients (72.1%) had unilateral mulberry hypertrophy. The most common concomitant pathologies were chronic rhinosinusitis and ostiomeatal complex disease; others included septal deviation, nasal polyposis, allergic rhinitis, and concha bullosa. Thirty-six patients (52.9%) with varying degrees of choanal/nasal obstruction were operated on with endoscopic excision to treat the mulberry hypertrophy. In all, most patients underwent some sort of surgery to treat either the mulberry hypertrophy or the accompanying sinonasal pathology. Based on our findings, we suggest a clinical staging system to serve as a way to standardize management and guide future basic and clinical research. PMID- 27551847 TI - Audiologic changes after pinna augmentation. AB - No studies to date have objectively assessed whether pinna morphology affects sound intensity detected within the external auditory canal (EAC). Commonly performed procedures on the EAC are carried out for acquired and congenital pathology, together with correction of ear deformities. Our aim was to use an experimental model to identify whether a relationship exists between pinna shape and its subsequent effect on the hearing subject. An anatomically accurate and life-size model made of rubber composite was used for this study. Serial sections (small wedge, defect open; small wedge, defect closed; large wedge, defect open; large wedge, defect closed [equivalent to a protruding ear]; and pinnectomy) were undertaken, and the sound intensity changes assessed at the junction between the EAC and middle ear (tympanic membrane position) using an AURICAL Plus (Otometrics; Taastrup, Denmark) sound processor. A statistically significant loss was demonstrated for wedge-excised models, which was greatest at 180 degrees azimuth. This loss was significantly reduced when the wedge defects were closed. A statistically significant improvement was demonstrated in the protruding ("bat") ear model compared with the normal ear at 0 degrees azimuth. In this model, gain in sound intensity is adversely affected by pinna wedge resection. Because this change may be increased in those with protruding ears, this factor is important to consider for all cosmetic and noncosmetic operations to the pinna, and it supports the notion that the pinna is not a simple funnel. PMID- 27551848 TI - Effects on auditory function of chronic exposure to electromagnetic fields from mobile phones. AB - The widespread use of mobile phones has given rise to apprehension regarding the possible hazardous health effects of high-frequency electromagnetic fields (EMFs) on auditory function. We conducted a study to investigate the effects of long term (>4 yr) exposure to EMFs emitted by mobile phones on auditory function. Our study population was made up of 40 healthy medical students-31 men and 9 women, aged 20 to 30 years (mean 22.7). Of this group, 31 subjects typically held their phone to the right ear and 9 to the left ear; the non-phone-using ear served as each subject's control ear. The phone-using subjects were also split into two groups of 20 based on the duration of their daily phone use (<=60 min vs. >60 min). All subjects underwent pure-tone audiometry, speech audiometry, impedance audiometry, and brainstem evoked response audiometry (BERA), and comparisons were made between the phone-using ear and the control ear and between the shorter and longer duration of daily use. We found no statistically significant differences in high-frequency pure-tone average between the phone-using ears and the control ears (p = 0.69) or between the shorter- and longer-duration phone-using ears (p = 0.85). Moreover, statistical analysis of BERA findings revealed no significant differences between the phone-using ears and the control ears in terms of wave I III, III-V, and I-V interpeak latencies (p = 0.59, 0.74 and 0.44, respectively). None of the subjects reported any subjective symptoms, such as headache, tinnitus, or sensations of burning or warmth behind, around, or on the phone using ear. We conclude that the long-term exposure to EMFs from mobile phones does not affect auditory function. PMID- 27551850 TI - Blastomycosis of the nose: A case report. AB - Blastomyces dermatitidis is a thermally dimorphic fungus endemic to the North American soil near the Mississippi, Ohio, and St. Lawrence river valleys, as well as the Great Lakes Basin. It is responsible for blastomycosis, a systemic pyogranulomatous disease. Blastomycosis of the head and neck is decidedly uncommon and often mistaken for cancer. There are only 3 previous case reports of blastomycosis presenting as an intranasal lesion. We report the unusual case of a 24-year-old man with blastomycosis presenting with a 4-week history of a progressively enlarging intranasal mass who had complete resolution of symptoms after treatment with itraconazole and surgical excision of the lesion. PMID- 27551849 TI - Postoperative hypofunctioning of the thyroid gland after total laryngectomy. AB - Primary laryngeal carcinoma is a common cancer, predominantly affecting males. Hypothyroidism is an undesirable sequela of both surgery and radiotherapy, the two most commonly used modalities of treatment. For advanced cases, standard treatment protocol includes total laryngectomy and neck dissection along with pre or postoperative radiotherapy. Hemithyroidectomy is also routinely performed as an integral part of total laryngectomy. In the present study, assessment of the function of the remaining half of the thyroid gland has been done in cases of total laryngectomies in combination with uni- or bilateral neck dissection and pre- or postoperative radiotherapy. This prospective, observational study was carried out for a period of 5 years in the Otolaryngology Department of R.G. Kar Medical College and Hospital, Kolkata, India, involving a dynamic cohort of patients with advanced laryngeal carcinoma (stage T3 or T4a) who underwent total laryngectomy (including hemithyroidectomy) and bilateral or unilateral neck dissection for primary laryngeal cancer along with preoperative and postoperative radiotherapy. Assessment of the thyroid function was based on the measurement of serum thyroid-stimulating hormone and free thyroxine levels. The results revealed that 23.8%, 45.2%, and 73.8% patients developed either clinical or subclinical hypothyroid state at 6, 12, and 24 weeks, respectively, after the surgery. The estimation of relative risk (RR) was found to be most prominent among the group belonging to the "preoperative radiation with bilateral neck dissection" group at all levels of assessments, but all of the RRs were found to be insignificant per their 95% confidence intervals. Superiority of any method could not be established or refuted firmly due to the small sample size of the study. We presume that in the future, a study with a larger sample size, involving a meta analysis of multicentric data, would be the most suitable method to throw some light on this issue. PMID- 27551851 TI - Clinical, functional, and surgical findings in chronic bilateral otitis media with effusion in childhood. AB - We conducted a prospective, observational study over a 3-year period to compare the clinical, functional, and surgical findings in children with chronic bilateral otitis media with effusion who underwent one of three different types of treatment. Our study population was made up of 150 patients-79 boys and 71 girls aged 24 to 84 months-who were randomly assigned to one of the three treatment groups of 50 patients each. One group was treated with myringotomy, tympanostomy tube insertion, and adenoidectomy (T+A group); another with a combination of physical conservative treatment and adenoidectomy (P+A group); and the third with physical conservative treatment alone (P-only group). Hearing levels and tympanogram trends were evaluated during a follow-up of 12 months. In the T+A group, we noted a stable normalization of hearing in 95 of the 100 ears. Treatment with the P+A combination resulted in an improvement of hearing in 79 ears, but the improvement was maintained in only 27 ears during 12 months of follow-up. In the group with the P-only regimen, an amelioration of hearing was registered in 76 ears, but it was unstable in all cases. A type A tympanogram was maintained during the follow-up period for 2 ears in the P+A group and for 4 ears in the P-only group. Myringotomy with a detailed examination of the tympanic cavity in all ears with prolonged abnormal audiologic results revealed that types C and B tympanograms, which were found in most ears in the P+A and P-only groups, corresponded to middle ear chronic inflammatory changes (retraction pockets, granulations, adhesions, etc.) Based on our findings, we conclude that the use of a physical conservative treatment with or without an adenoidectomy does not prevent the development of chronic adhesive and purulent otitis media. PMID- 27551852 TI - Idiopathic nasal bone osteitis: A preliminary report on a recently recognized entity. AB - Osteitis of the nasal bones is a rare disease; when it occurs, it usually has a known etiology. To the best of our knowledge, idiopathic nasal bone osteitis (NBO) has not been described before. We conducted a study to analyze the behavior of idiopathic NBO and its outcome and to determine a cutoff level for diagnosis using technetium-99m-methylene-diphosphonate (Tc-MDP) bone scanning. This retrospective, controlled analysis involved 9 women (mean age: 44 yr) who had been admitted to an otolaryngology department in Israel with idiopathic NBO over a 5-year period. Clinical evaluation, isotopic evaluation, and computed tomography were done. A lesion-to-nonlesion ratio was calculated between an area of interest on the nasal bone and a reference point (L/R ratio). The same ratio was calculated for a control group of 20 subjects. All the Tc-MDP scans in the study group were suggestive of osteitis. Intravenous antibiotic treatment was effective in all cases. A high degree of accuracy was achieved with cutoff L/R ratios of 2.05 for planar views and 2.34 for single-photon emission computed tomography views. PMID- 27551853 TI - Epithelioid hemangioendothelioma of tongue presenting as a papilloangioma in a pregnant woman. PMID- 27551854 TI - Analysis of vocal and swallowing functions after horizontal glottectomy. AB - We conducted a cross-sectional study to assess vocal and swallowing functions after horizontal glottectomy. Our study population was made up of 22 men aged 45 to 72 years (mean: 58.3) who underwent horizontal glottectomy and completed at least 1 year of follow-up. To compare postoperative results, 20 similarly aged men were included as a control group; all glottectomy patients and all controls were smokers. We used three methods-acoustic and aerodynamic voice analyses, the GRBAS (grade, roughness, breathiness, asthenicity, and strain) scale, and the voice handicap index-30 (VHI-30)-to assess vocal function objectively, perceptually, and subjectively, respectively. We also assessed swallowing function objectively by fiberoptic endoscopic evaluation of swallowing (FEES) and subjectively with the M.D. Anderson dysphagia inventory (MDADI). The 22 patients were also subcategorized into three groups according to the extent of their arytenoid cartilage resection, and their outcomes were compared. Acoustic and aerodynamic analyses showed that the mean maximum phonation time was significantly shorter and the fundamental frequency was significantly lower in the glottectomy group than in the controls (p = 0.001 for both), and that the mean jitter and shimmer values and the mean harmonics-to-noise ratio were all significantly higher (p = 0.001 for all); there were no significant differences among the three arytenoid subgroups. Self-assessments revealed that there were no statistically significant differences among the three subgroups in GRBAS scale scores except for the breathiness score (p = 0.045), which was lower in the arytenoid preservation subgroup than in the total resection subgroup; there were no statistically significant differences among the three subgroups in VHI-30 scores. Finally, swallow testing found no statistically significant differences in FEES scores or MDADI scores. We conclude that horizontal glottectomy caused a deterioration in vocal function, but swallowing function was satisfactory. PMID- 27551856 TI - A systematic review of the relationship factor between women and health professionals within the multivariant analysis of maternal satisfaction. AB - INTRODUCTION: personalised support provided to women by health professionals is one of the prime factors attaining women's satisfaction during pregnancy and childbirth. However the multifactorial nature of 'satisfaction' makes difficult to assess it. Statistical multivariate analysis may be an effective technique to obtain in depth quantitative evidence of the importance of this factor and its interaction with the other factors involved. This technique allows us to estimate the importance of overall satisfaction in its context and suggest actions for healthcare services. METHODS: systematic review of studies that quantitatively measure the personal relationship between women and healthcare professionals (gynecologists, obstetricians, nurse, midwifes, etc.) regarding maternity care satisfaction. The literature search focused on studies carried out between 1970 and 2014 that used multivariate analyses and included the woman-caregiver relationship as a factor of their analysis. RESULTS: twenty-four studies which applied various multivariate analysis tools to different periods of maternity care (antenatal, perinatal, post partum) were selected. The studies included discrete scale scores and questionnaires from women with low-risk pregnancies. The "personal relationship" factor appeared under various names: care received, personalised treatment, professional support, amongst others. The most common multivariate techniques used to assess the percentage of variance explained and the odds ratio of each factor were principal component analysis and logistic regression. DISCUSSION: the data, variables and factor analysis suggest that continuous, personalised care provided by the usual midwife and delivered within a family or a specialised setting, generates the highest level of satisfaction. In addition, these factors foster the woman's psychological and physiological recovery, often surpassing clinical action (e.g. medicalization and hospital organization) and/or physiological determinants (e.g. pain, pathologies, etc.). PMID- 27551855 TI - Differential Gel Electrophoresis (DIGE) Evaluation of Naphthoimidazoles Mode of Action: A Study in Trypanosoma cruzi Bloodstream Trypomastigotes. AB - BACKGROUND: The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from beta lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite. METHODOLOGY/PRINCIPAL FINDINGS: The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase. CONCLUSION/SIGNIFICANCE: Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents. PMID- 27551857 TI - 'They aren't really black fellas but they are easy to talk to': Factors which influence Australian Aboriginal women's decision to disclose intimate partner violence during pregnancy. AB - OBJECTIVES: intimate partner violence is a significant global health problem but remains largely hidden. Understanding decisions about whether or not to disclose violence in response to routine enquiry in health settings can inform safe and responsive systems. Elevated rates of violence and systematic disadvantage found among Indigenous women globally, can impact on their decisions to disclose violence. This study aimed to test, among Indigenous women, a model for decisions on whether to disclose intimate partner violence in the context of antenatal routine screening. DESIGN: we employed Qualitative Configurative Analysis, a method developed for the social sciences to study complex phenomena with intermediate sample sizes. Data were drawn from single semi- structured interviews with Indigenous women 28+ weeks pregnant attending antenatal care. Interviews addressed decisions to disclose recent intimate partner violence in the context of routine enquiry during the antenatal care. Interview transcripts were binary coded for conditions identified a priori from the model being tested and also from themes identified within the current study and analysed using Qualitative Configurative Analysis to determine causal conditions for the outcome of disclosure or non-disclosure of violence experienced. SETTINGS: five Aboriginal and Maternal Infant Health Services (two urban and three regional), and one mainstream hospital, in New South Wales, Australia. PARTICIPANTS: indigenous women who had experienced partner violence in the previous year and who had been asked about this as part of an antenatal booking-in visit. Of the 12 participants six had elected to disclose their experience of violence to the midwife, and six had chosen not to do so. FINDINGS: pathways to disclosure and non-disclosure were mapped using Qualitative Configurative Analysis. Conditions relevant to decisions to disclose were similar to the conditions for non Aboriginal women found in our earlier study. Unique to Aboriginal women's decisions to disclose abuse was cultural safety. Cultural safety included elements we titled: Borrowed trust, Build the relationship first, Come at it slowly and People like me are here. The absence of cultural safety Its absence was also a factor in decisions not to disclose experiences of violence by this group of women. KEY CONCLUSIONS: cultural safety was central to Indigenous women's decision to disclose violence and processes for creating safety are identified. Other forms of safety which influenced disclosure included: safety from detection by the abuser; safety from shame; and safety from institutional control. Disclosure was promoted by direct asking by the midwife and a perception of care. Non-disclosure was associated with a lack of care and a lack of all four types of safety. Experiences of institutional racism were associated with Indigenous women's perceived risk of control by others, particularly child protection services. IMPLICATIONS FOR PRACTICE: policies to ask abuse questions at first visits and models where continuity of care is not maintained, are problematic for Aboriginal women, among whom relationship building is important as is ample warning about questions to be asked. Strategies are needed to build cultural safety to counter widespread racism and promote safe opportunities for Indigenous women to disclose intimate partner violence and receive support. Elements of cultural safety are necessary for vulnerable or marginalised populations to fully utilise available health services. PMID- 27551858 TI - Estimating pediatric asthma prevalence in rural senegal: A cross-sectional survey. AB - RATIONALE: In Senegal, the prevalence of childhood asthma and utilization of appropriate asthma therapies is unknown. METHODOLOGY: We used the International Study of Asthma and Allergies in Childhood (ISAAC) survey instrument to assess childhood respiratory health in rural Senegal. We interviewed the caregivers of children aged 5 through 8 years of age in the four largest Niakhar villages in August 2012. RESULTS: We interviewed 1,103 primary caregivers for 1,513 children, representing 91% of all age-eligible children in the study area. Overall, 206 (14%) children had wheeze at any time in the past, 130 (9%) had wheeze within the past year, and only 41 (3%) reported a clinical diagnosis of asthma. Among children with wheeze within the past year, 81 (62%) had symptoms of severe asthma. Nocturnal cough was reported in 186 (14%) children who denied any history of wheezing illness. Only four (3%) children with wheeze in the past year had ever received bronchodilator therapy. Children with wheeze in the past year were significantly more likely to seek medical care for respiratory symptoms and to be perceived as less healthy than their peers. Children of lower socioeconomic status were significantly more likely to have wheeze. CONCLUSIONS: Nearly one in ten children in Niakhar, Senegal had symptoms suggestive of asthma; however, few children have a diagnosis of asthma or use appropriate therapies. This study highlights an opportunity to raise community awareness of asthma in rural Senegal and to increase access to appropriate medical therapies. Pediatr Pulmonol. 2017;52:303-309. (c) 2016 Wiley Periodicals, Inc. PMID- 27551859 TI - Study of conformation and thermodynamics of alpha-amylase interaction with ethylene in vitro. AB - In this article, the conformation and thermodynamics of alpha-amylase interaction with ethylene in vitro were investigated. The ultraviolet (UV) absorption showed a strong peak of alpha-amylase treated with 6.04, 29.32 and 262.11MUmolL(-1) ethylene appears at ~222nm and a weak peak at 278nm blue-shifted 1nm. Circular dichroism (CD) spectra indicated that the conformations of alpha-amylase treated with 29.32 and 262.11MUmolL(-1) ethylene were obviously changed in which alpha helix content were decreased by 20 and 31% respectively, and beta-sheet, beta turn and random coil contents were increased by contrast. Fluorescence spectra suggested that the peak intensities of alpha-amylase at 342nm were obviously increased with the ethylene increase from 6.04 to 525.75MUmolL(-1) and more than control group. The binding constants K between ethylene and alpha-amylase were 3.318*10(6), 4.407*10(6) and 5.125*10(6)Lmol(-1) at 288, 298 and 308K, respectively. And the calculated values of DeltaH(0) and DeltaS(0) are positive, which suggests that the interaction between ethylene and alpha-amylase is an endothermic reaction. The negative DeltaG(0) values implied that the direct effect of ethylene on alpha-amylase conformation was spontaneous. The possible reason is that ethylene molecules were easily embedded into the interior of alpha amylase in term of the hydrophobic force between alpha-amylase and ethylene, causing the conformation and thermodynamics changes of alpha-amylase. PMID- 27551860 TI - Phytoremediation of industrial mines wastewater using water hyacinth. AB - The wastewater at Sukinda chromite mines (SCM) area of Orissa (India) showed high levels of toxic hexavalent chromium (Cr VI). Wastewater from chromium contaminated mines exhibit potential threats for biotic community in the vicinity. The aim of the present investigation is to develop a suitable phytoremediation technology for the effective removal of toxic hexavalent chromium from mines wastewater. A water hyacinth species Eichhornia crassipes was chosen to remediate the problem of Cr (VI) pollution from wastewater. It has been observed that this plant was able to remove 99.5% Cr (VI) of the processed water of SCM in 15 days. This aquatic plant not only removed hexavalent Cr, but is also capable of reducing total dissolved solids (TDS), biological oxygen demand (BOD), chemical oxygen demand (COD), and other elements of water also. Large-scale experiment was also performed using 100 L of water from SCM and the same removal efficiency was achieved. PMID- 27551861 TI - Early Discharge in Low-Risk Patients Hospitalized for Acute Coronary Syndromes: Feasibility, Safety and Reasons for Prolonged Length of Stay. AB - INTRODUCTION: Length of hospital stay (LHS) is an indicator of clinical effectiveness. Early hospital discharge (<=72 hours) is recommended in patients with acute coronary syndromes (ACS) at low risk of complications, but reasons for prolonged LHS poorly reported. METHODS: We collected data of ACS patients hospitalized at the Geneva University Hospitals from 1st July 2013 to 30th June 2015 and used the Zwolle index score to identify patients at low risk (<= 3 points). We assessed the proportion of eligible patients who were successfully discharged within 72 hours and the reasons for prolonged LHS. Outcomes were defined as adherence to recommended therapies, major adverse events at 30 days and patients' satisfaction using a Likert-scale patient-reported questionnaire. RESULTS: Among 370 patients with ACS, 255 (68.9%) were at low-risk of complications but only 128 (50.2%)were eligible for early discharge, because of other clinical reasons for prolonged LHS (e.g. staged coronary revascularization, cardiac monitoring) in 127 patients (49.8%). Of the latter, only 45 (35.2%) benefitted from an early discharge. Reasons for delay in discharge in the remaining 83 patients (51.2%) were mainly due to delays in additional investigations, titration of medical therapy, admission or discharge during weekends. In the early discharge group, at 30 days, only one patient (2.2%) had an adverse event (minor bleeding), 97% of patients were satisfied by the medical care. CONCLUSION: Early discharge was successfully achieved in one third of eligible ACS patients at low risk of complications and appeared sufficiently safe while being overall appreciated by the patients. PMID- 27551863 TI - The effect of sleep disturbance in patients with chronic dizziness. AB - CONCLUSIONS: The comorbidity of sleep disturbance with chronic dizziness in women was related to the intensity of distress and interference with their lives due to dizziness, although it was not related to objective variables of dizziness. In addition, the presence of sleep disturbance was associated with severe anxiety and depression, and low health-related quality-of-life (QoL). OBJECTIVES: This study investigated the effect of sleep disturbance in patients with chronic dizziness on symptoms of dizziness, handicaps due to dizziness, health-related QoL, and emotional distress. METHOD: The participants of this study were 252 in patients with chronic dizziness. Participants completed questionnaires containing the Dizziness Handicap Inventory (DHI, three sub-scales: Physical [DHI-P], Emotional [DHI-E], and Functional [DHI-F] scores), Pittsburgh sleep quality index (PSQI-J), Hospital Anxiety and Depression Scale (HADS), and Medical Outcomes Study 8-items Short Form Health Survey (SF-8, health-related QoL). The participants then underwent gravity center fluctuation measurement as an objective indicator of the severity of dizziness. RESULTS: The prevalence of sleep disturbance (PSQI-J global score ?6) was 65.1% in these participants. Two way ANOVA of the DHI scores showed significant interaction between sleep disturbance and sex in DHI total, DHI-E score, and DHI-F score, indicating that these scores were higher in women with sleep disturbance. Regarding DHI-P score, only the main effect of sex was significant (women > men). Sleep disturbance had no significant effect on objective indicators of severity of dizziness. Patients with sleep disturbance had significantly higher HADS scored and a lower SF-8 scored than patients without sleep disturbance. PMID- 27551862 TI - Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation. AB - BACKGROUND AND OBJECTIVE: The aim of this study was to determine if X-ray micro computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. STUDY DESIGN/MATERIALS AND METHODS: A surgical CO2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X ray images with those visible by classic light microscopy histology were made. RESULTS: We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. CONCLUSION: We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27551864 TI - DNA-Mediated Morphological Control of Silver Nanoparticles. AB - It is demonstrated that DNA can be used to control the synthesis of silver nanoplates with different morphologies using spherical silver seeds. UV-vis spectroscopy, transmission electron microscopy, scanning electron microscopy, X ray photoelectron spectroscopy, and Raman spectroscopy are used to characterize the synthesized nanoparticles. Silver nanoprisms are encoded by poly C and poly G, while silver flower bouquets and silver nanodiscs are synthesized using poly A and poly T, respectively. The length of DNA is found to have little effect on the morphology of silver nanoparticles. Moreover, the synthesized silver nanoplates are found to have high surface enhanced Raman scattering enhancement ability, good antibacterial activity, and good biocompatibility. These discoveries will broaden the application of DNA in nanoscience and will provide a new platform to investigate the interaction between DNA sequences and silver nanoparticles. PMID- 27551865 TI - Resonant Charge Transport in Conjugated Molecular Wires beyond 10 nm Range. AB - Using a scanning tunneling microscope, we measured high-bias conductance of single polyporphyrin molecular wires with lengths from 1.3 to 13 nm. We observed several remarkable transport characteristics, including multiple sharp conductance peaks, conductances as high as 20 nS in wires with lengths of >10 nm, and nearly length-independent conductance (attenuation <0.001 A(-1)). We carried out first-principles simulations on myriad metal-molecule-metal junctions. The simulations revealed that the measured conductance is coherent resonant transport via a delocalized molecular orbital. PMID- 27551867 TI - [Not Available]. AB - Deep brain stimulation for psychiatric disorders Deep brain stimulation is an established treatment for movement disorders. It has been proven to be a safe method; only minor complications have been reported in larger studies. New indications for deep brain stimulation are under investigation; among them major depressive disorder and obsessive-compulsive disorder. Deep brain stimulation for severe and therapy-resistant major depressive disorder and obsessive compulsive disorder shows promising results. However, the experience of deep brain stimulation in psychiatric disorders is limited. Several potential target areas for stimulation have been presented; which are the most effective is still an open question. Deep brain stimulation in psychiatric disorders is a highly experimental treatment and should only be performed by a multidisciplinary team with extensive experience with deep brain stimulation in other conditions. PMID- 27551866 TI - Gene Cloning, Expression and Enzyme Activity of Vitis vinifera Vacuolar Processing Enzymes (VvVPEs). AB - Vacuolar processing enzymes (VPEs) have received considerable attention due to their caspase-1-like activity and ability to regulate programmed cell death (PCD), which plays an essential role in the development of stenospermocarpic seedless grapes ovules. To characterize VPEs and the relationship between stenospermocarpic grapes and the VPE gene family, we identified 3 Vitis vinifera VPE genes (VvbetaVPE, VvgammaVPE, and VvdeltaVPE) from the PN40024 grape genome and cloned the full-length complementary DNAs (cDNAs) from the 'Vitis vinifera cv. Pinot Noir' and 'Vitis vinifera cv. Thompson Seedless' varietals. Each of the VPEs contained a typical catalytic dyad [His (177), Cys (219)] and substrate binding pocket [Arg (112), Arg (389), Ser (395)], except that Ser (395) in the VvgammaVPE protein sequence was replaced with alanine. Phylogenetic analysis of 4 Arabidopsis thaliana and 6 Vitis vinifera VPEs revealed that the 10 VPEs form 3 major branches. Furthermore, the 6 grapevine VPEs share a similar gene structure, with 9 exons and 8 introns. The 6 grapevine VPEs are located on 3 different chromosomes. We also tested the enzymatic activity of recombinant VPEs expressed in the Pichia Pastoris expression system and found that the VvVPEs exhibit cysteine peptidase activity. Tissue-specific expression analysis showed that VvdeltaVPE is only expressed in flowers, buds and ovules, that VvgammaVPE is expressed in various tissues, and that VvbetaVPE was expressed in roots, flowers, buds and ovules. The results of quantitative real-time PCR (qRT-PCR) suggested that VvbetaVPE in seeded grapes increased significantly at 30 days after full bloom (DAF), close to the timing of endosperm abortion at 32 DAF. These results suggested that VvbetaVPE is related to ovule abortion in seedless grapes. Our experiments provide a new perspective for understanding the mechanism of stenospermocarpic seedlessness and represent a useful reference for the further study of VPEs. PMID- 27551868 TI - [Not Available]. AB - Familial Mediterranean fever - an important disease in a globalised world Familial Mediterranean fever (FMF) is characterized by recurrent febrile attacks during 1/2-3 days associated with peritonitis, pleuritis and arthritis. FMF is the most common monogenic autoinflammatory disease in the world, with over 100 000 affected individuals. It is particularly common in individuals with an origin in the eastern Mediterranean Basin, where the disease has a prevalence of 100-200 per 100 000. The gene for FMF (MEFV) was identified in 1997 with an autosomal recessive inheritance; however, a significant proportion (~25%) of clinical patients lack two mutations. MEFV codes for the protein pyrin, whose exact function still needs to be defined. The most serious complication of FMF is amyloid A amyloidosis, in particular renal amyloidosis. FMF is efficiently treated with daily doses of colchicine resulting in an almost normal life expectancy and amyloidosis confined to non-compliant patients. In today's globalized world we need to adapt to a new context that includes inherited conditions, which have historically been uncommon in our part of the world. One of these conditions is FMF, that should primarily be suspected in individuals with an origin in the eastern Mediterranean Basin and recurrent attacks of fever. PMID- 27551869 TI - [Not Available]. AB - Laparoscopic surgery for colorectal cancer in Sweden has previously been performed infrequently but is presently increasing, and in 2014 more than one fourth of all patients with colorectal cancer underwent laparoscopic resection. Regional differences are decreasing but substantial variation persists with regard to individual hospitals and the use of laparoscopy. All Swedish patients undergoing resection for cancer in the ascending and sigmoid colon between 2012 2014 (n=8269; laparoscopic resection 17%) were assessed with regard to patient demography and short-term outcome. The present investigation demonstrated that open surgery was more often performed in patients with locally advanced cancer or with metastatic disease and that laparoscopically operated patients were slightly younger and had less comorbidity. Short term surgical outcome was better in patients who underwent laparoscopy, a difference which may be attributed to a certain patient selection demonstrated in the present investigation. The number of retrieved lymph nodes was comparable and hospital stay was two days shorter in patients with laparoscopic resection. PMID- 27551870 TI - [Not Available]. PMID- 27551871 TI - [Not Available]. PMID- 27551872 TI - [Not Available]. PMID- 27551873 TI - [Not Available]. PMID- 27551874 TI - [Not Available]. PMID- 27551876 TI - [Not Available]. PMID- 27551875 TI - [Not Available]. PMID- 27551877 TI - Results of peripheral bypass surgery in patients with critical limb ischemia (CRITISCH registry). AB - AIM: On the basis of the CRITISCH registry outcomes in patients with critical limb ischemia (CLI) undergoing lower extremity bypass surgery were analyzed according to the site of distal anastomosis and type of bypass material. PATIENTS AND METHODS: A total of 284 patients with lower extremity bypasses consisting of 75 patients with bypasses above the knee (group 1), 80 with bypasses below the knee (group 2) and 129 crural or pedal bypasses (group 3) were included in the study. Altogether, 159 autologous saphenous vein grafts and 125 synthetic grafts were used. RESULTS: There were no perioperative complications in 191 out of the 284 patients (67.3 %) and 236 of the 284 patients (83.1 %) had open bypasses at hospital discharge. An uneventful postoperative course was observed in 76 % of the patients in group 1, 62.5 % in group 2 and 65.1 % in group 3. Amputation-free survival was 86 % at 1 year in group 1, 65 % in group 2 and 69 % in group 3. For bypasses above the knee synthetic grafts were at least not inferior to vein grafts (amputation-free survival at 1 year: prosthetic bypasses 92 % and saphenous vein grafts 71 %, p = 0.147), whereas in the crural/pedal bypass group vein grafts showed better amputation-free survival at 1 year (76 %) compared with synthetic bypasses (56 %, p = 0.105). Patients with a PREVENT III (PIII) CLI risk score <=3 exhibited better amputation-free survival at 1 year (78 %) compared to patients with a PIII CLI risk score of 4-7 (69 %, p = 0.053). The same applied to patients with Rutherford class 4 vs. Rutherford class 6 CLI. CONCLUSION: In patients with CLI and above-knee bypasses, vein grafts confer no benefits compared with synthetic grafts for at least 1 year follow-up; however, in the case of more distal anastomoses vein grafts should be preferred. PMID- 27551879 TI - Implant-Abutment Contact Surfaces and Microgap Measurements of Different Implant Connections Under 3-Dimensional X-Ray Microtomography. AB - PURPOSE: The presence of a microgap between implant and abutment could produce a bacterial reservoir which could interfere with the long-term health of the periimplant tissues. The aim of this article was to evaluate, by x-ray 3 dimensional microtomography, implant-abutment contact surfaces and microgaps at the implant-abutment interface in different types of implant-abutment connections. MATERIALS AND METHODS: A total of 40 implants were used in this in vitro study. Ten implants presented a screw-retained internal hexagon abutment (group I), 10 had a Morse Cone taper internal connection (group II), 10 another type of Morse Cone taper internal connection (group III), and 10 had a screwed trilobed connection (group IV). RESULTS: In both types of Morse Cone internal connections, there was no detectable separation at the implant-abutment in the area of the conical connection, and there was an absolute congruity without any microgaps between abutment and implant. No line was visible separating the implant and the abutment. On the contrary, in the screwed abutment implants, numerous gaps and voids were present. CONCLUSIONS: The results of this study support the hypothesis that different types of implant-abutment joints are responsible for the observed differences in bacterial penetration. PMID- 27551878 TI - Spectral prior image constrained compressed sensing (spectral PICCS) for photon counting computed tomography. AB - Photon-counting computed tomography (PCCT) is an emerging imaging technique that enables multi-energy imaging with only a single scan acquisition. To enable multi energy imaging, the detected photons corresponding to the full x-ray spectrum are divided into several subgroups of bin data that correspond to narrower energy windows. Consequently, noise in each energy bin increases compared to the full spectrum data. This work proposes an iterative reconstruction algorithm for noise suppression in the narrower energy bins used in PCCT imaging. The algorithm is based on the framework of prior image constrained compressed sensing (PICCS) and is called spectral PICCS; it uses the full-spectrum image reconstructed using conventional filtered back-projection as the prior image. The spectral PICCS algorithm is implemented using a constrained optimization scheme with adaptive iterative step sizes such that only two tuning parameters are required in most cases. The algorithm was first evaluated using computer simulations, and then validated by both physical phantoms and in vivo swine studies using a research PCCT system. Results from both computer-simulation and experimental studies showed substantial image noise reduction in narrow energy bins (43-73%) without sacrificing CT number accuracy or spatial resolution. PMID- 27551880 TI - Eating disorders in children and adolescents: what does the gynecologist need to know? AB - PURPOSE OF REVIEW: The purpose of this review is to discuss the diagnosis, medical complications, and treatment of eating disorders as defined by the newly released Diagnostic and Statistical Manual, 5th edition. RECENT FINDINGS: With the introduction of the Diagnostic and Statistical Manual, 5th edition, the diagnostic criteria for anorexia nervosa and bulimia nervosa have been revised to better capture the varied presentations of patients with eating disorders. In addition, new eating disorder diagnoses including binge-eating disorder, characterized by recurrent bingeing without associated compensatory behaviors, and avoidant/restrictive food intake disorder, characterized by a restrictive eating pattern without associated body dysmorphism, allow for increased recognition, diagnosis, and treatment of disordered eating patterns. In addition to a high mortality rate, eating disorders are associated with serious medical sequelae secondary to malnutrition and disordered behaviors, including disturbances of the cardiovascular, neurologic, gastrointestinal, reproductive, and skeletal systems. Early diagnosis and family-based treatment are associated with improved outcomes in children and adolescents. SUMMARY: Eating disorders are illnesses with biological, psychological, and social implications that commonly present in childhood and adolescence. Gynecologists are on the front line for the screening and diagnosis of eating disorders in adolescent women. PMID- 27551881 TI - Laparoscopic prolapse surgery: types and evidence. AB - PURPOSE OF REVIEW: Recommendations for the surgical treatment of pelvic organ prolapse have undergone significant changes over the last few decades.First described to be too difficult, the laparoscopic technique has gained popularity but is still controversial. The recent warning on vaginal mesh was the sign of revival and we start now to have many articles published on results and on techniques for laparoscopic prolapse repair. RECENT FINDINGS: If nothing is new in the comparison of the routes including vaginal mesh placement, the new articles are very interesting in terms of technical information and recommendations. Those articles are very important and help us understand some failures in the laparoscopic approach mainly in the anterior compartment. SUMMARY: New models have been created and eventually in the future, we will be able to simulate the repair on our own patients and to assess virtually the mobility of each compartment preoperatively. This will allow us to adjust and tailor the treatment to each patient. PMID- 27551883 TI - Cannabinoids and post-traumatic stress disorder: clinical and preclinical evidence for treatment and prevention. AB - There is substantial evidence from studies in humans and animal models for a role of the endocannabinoid system in the control of emotional states. Several studies have shown an association between exposure to trauma and substance use. Specifically, it has been shown that there is increased prevalence of cannabis use in post-traumatic stress disorder (PTSD) patients and vice versa. Clinical studies suggest that PTSD patients may cope with their symptoms by using cannabis. This treatment-seeking strategy may explain the high prevalence of cannabis use among individuals with PTSD. Preliminary studies in humans also suggest that treatment with cannabinoids may decrease PTSD symptoms including sleep quality, frequency of nightmares, and hyperarousal. However, there are no large-scale, randomized, controlled studies investigating this specifically. Studies in animal models have shown that cannabinoids can prevent the effects of stress on emotional function and memory processes, facilitate fear extinction, and have an anti-anxiety-like effect in a variety of tasks. Moreover, cannabinoids administered shortly after exposure to a traumatic event were found to prevent the development of PTSD-like phenotype. In this article, we review the existing literature on the use of cannabinoids for treating and preventing PTSD in humans and animal models. There is a need for large-scale clinical trials examining the potential decrease in PTSD symptomatology with the use of cannabis. In animal models, there is a need for a better understanding of the mechanism of action and efficacy of cannabis. Nevertheless, the end result of the current clinical and preclinical data is that cannabinoid agents may offer therapeutic benefits for PTSD. PMID- 27551884 TI - Palladium-Catalyzed Norbornene-Mediated Tandem ortho-C-H-Amination/ipso-C-I Cyanation of Iodoarenes: Regiospecific Synthesis of 2-Aminobenzonitrile. AB - Efficient tandem ortho-C-H-amination/ipso-cyanation of iodoarenes was accomplished under a norbornene-mediated Pd-catalyzed process. A series of functionalized 2-aminobenzonitriles with much potential in the pharmaceutical industry were obtained by this protocol. This strategy was successfully employed for substitution with two cyano and four amino functionalities in an arene unit in one step under specified conditions. PMID- 27551882 TI - Peginesatide for the treatment of anemia due to chronic kidney disease - an unfulfilled promise. AB - INTRODUCTION: The introduction of recombinant human erythropoietin revolutionized the management of anemia in patients with chronic kidney disease (CKD). In order to circumvent costly recombinant DNA technology, synthetic chemistry techniques were used to manufacture peginesatide, a synthetic peptide that bore no resemblance to previous erythropoiesis-stimulating agents (ESAs), and yet was capable of stimulating erythropoiesis. Compared with other ESAs, peginesatide was deemed to have advantages related to immunogenicity, administration schedule, and cost. Marketing approval was restricted to CKD patients on dialysis because cardiovascular events were more common with peginesatide than with darbepoetin in non-dialysis CKD patients. Unfortunately, unexplained serious adverse drug reactions (sADR) led to quick withdrawal of peginesatide from the market. AREAS COVERED: This review describes the efficacy and safety of peginesatide in pre approval clinical trials, sADRs after marketing approval, and lessons learned during its short life-span. EXPERT OPINION: The case of peginesatide illustrates the difficulties in detecting rare sADRs in trials with limited patient populations and the need for improved pharmacovigilance after marketing approval. However, the need for simpler drug production methods as a result of non dependence on recombinant DNA techniques and mammalian cell lines remains. Lessons learned during the scientific development of peginesatide can be used in developing other drugs. PMID- 27551885 TI - Click Dehydrogenation of Carbon-Substituted nido-5,6-C2B8H12 Carboranes: A General Route to closo-1,2-C2B8H10 Derivatives. AB - Triethylamine-catalyzed dehydrogenation of carbon-disubstituted dicarbaboranes 5,6-R2-nido-5,6-C2B8H10 [1, where R = H (1a), Me (1b), and Ph (1c)] in refluxing acetonitrile leads to a high-yield (up to 85-95%) formation of a series of dicarbaboranes 1,2-R2-closo-1,2-C2B8H8 (2). The monosubstituted 6-R-nido-5,6 C2B8H11 (3) analogues [where R = Ph (3a), naph (1-naphthyl; 3b), Bu (3c)] afforded 1-R-1,2-closo C2B8H9 (4) isomers [where R = Ph (4a), naph (4b), n-Bu (4c)] as the main products; compounds 4a and 4c were accompanied by 2-R-1,2 C2B8H9 (5) isomers (total yields up to 90%), with the 4/5 molar ratio being strongly dependent on the nature of R (4:1 and 1:1, respectively). All of these cage-closure reactions are supposed to proceed via the stage of the corresponding Et3NH(+) salts of nido anions [5,6-R2-5,6-C2B8H9](-) (1(-)) and [6-R-5,6 C2B8H10](-) (3(-)), which lose H2 and Et3N upon heating (dehydrodeamination). The cage-closure mechanisms leading to closo isomers 2, 4, and 5 have been substantiated by B3LYP/6-31+G* calculations of the reaction profile for a simple 1a(-) -> 2a + H(-) conversion. All of the compounds isolated have been characterized by multinuclear ((11)B, (1)H, and (13)C) NMR spectroscopy, mass spectrometry, and elemental analyses, and the structure of 1-Ph-closo-1,2-C2B8H9 (4a) was established by an X-ray diffraction study. PMID- 27551886 TI - Spontaneous, Solvent-Free, Polymer-Templated, Solid-Solid Transformation of Thin Metal Films into Nanoparticles. AB - Metal nanoparticles have unusual optical, electronic, sensing, recognition, catalytic, and therapeutic properties. They are expected to form the basis of many of the technological and biological innovations of this century. A prerequisite for future applications using nanoparticles as functional entities is control of the shape, size, and homogeneity of these nanoparticles and of their interparticle spacing and arrangement on surfaces, between electrodes, or in devices. Here, we demonstrate that thin films of gold, silver, and copper sputter-deposited onto the surface of an organic polymer poly[[1,1':4',1" terphenyl]-4,4"-diyl(2-bromo-1-carboxyethylidene)] (PTBC) undergo spontaneous solid-solid transformation into nanoparticles. Furthermore, we show that, by varying the thickness of the films, the volume-to-surface ratio of the polymer substrate, and the amount of plasticizer, it is possible to control the rate of transformation and the morphology of the nanoparticles formed. PTBC containing Au nanoparticles was found to enhance the cell adhesion and proliferation. To the best of our knowledge, our findings constitute the first experimental evidence of spontaneous, room-temperature, solid-solid transformation of metal films sputtered onto the surface of an organic polymeric substrate into nanoparticles (crystals). PMID- 27551887 TI - Toward High-Performance Hematite Nanotube Photoanodes: Charge-Transfer Engineering at Heterointerfaces. AB - Vertically ordered hematite nanotubes are considered to be promising photoactive materials for high-performance water-splitting photoanodes. However, the synthesis of hematite nanotubes directly on conducting substrates such as fluorine-doped tin oxide (FTO)/glass is difficult to be achieved because of the poor adhesion between hematite nanotubes and FTO/glass. Here, we report the synthesis of hematite nanotubes directly on FTO/glass substrate and high performance photoelectrochemical properties of the nanotubes with NiFe cocatalysts. The hematite nanotubes are synthesized by a simple electrochemical anodization method. The adhesion of the hematite nanotubes to the FTO/glass substrate is drastically improved by dipping them in nonpolar cyclohexane prior to postannealing. Bare hematite nanotubes show a photocurrent density of 1.3 mA/cm(2) at 1.23 V vs a reversible hydrogen electrode, while hematite nanotubes with electrodeposited NiFe cocatalysts exhibit 2.1 mA/cm(2) at 1.23 V which is the highest photocurrent density reported for hematite nanotubes-based photoanodes for solar water splitting. Our work provides an efficient platform to obtain high-performance water-splitting photoanodes utilizing earth-abundant hematite and noble-metal-free cocatalysts. PMID- 27551888 TI - Temperature-Dependent Wsm1 and Wsm2 Gene-Specific Blockage of Viral Long-Distance Transport Provides Resistance to Wheat streak mosaic virus and Triticum mosaic virus in Wheat. AB - Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) are economically important viral pathogens of wheat. Wheat cvs. Mace, carrying the Wsm1 gene, is resistant to WSMV and TriMV, and Snowmass, with Wsm2, is resistant to WSMV. Viral resistance in both cultivars is temperature sensitive and is effective at 18 degrees C or below but not at higher temperatures. The underlying mechanisms of viral resistance of Wsm1 and Wsm2, nonallelic single dominant genes, are not known. In this study, we found that fluorescent protein-tagged WSMV and TriMV elicited foci that were approximately similar in number and size at 18 and 24 degrees C, on inoculated leaves of resistant and susceptible wheat cultivars. These data suggest that resistant wheat cultivars at 18 degrees C facilitated efficient cell-to-cell movement. Additionally, WSMV and TriMV efficiently replicated in inoculated leaves of resistant wheat cultivars at 18 degrees C but failed to establish systemic infection, suggesting that Wsm1- and Wsm2-mediated resistance debilitated viral long-distance transport. Furthermore, we found that neither virus was able to enter the leaf sheaths of inoculated leaves or crowns of resistant wheat cultivars at 18 degrees C but both were able to do so at 24 degrees C. Thus, wheat cvs. Mace and Snowmass provide resistance at the long-distance movement stage by specifically blocking virus entry into the vasculature. Taken together, these data suggest that both Wsm1 and Wsm2 genes similarly confer virus resistance by temperature-dependent impairment of viral long-distance movement. PMID- 27551889 TI - Avermectin Confers Its Cytotoxic Effects by Inducing DNA Damage and Mitochondria Associated Apoptosis. AB - Avermectin (AVM) has been widely used in agriculture and animal husbandry on the basis of its broad spectrum of effective anthelmintic activity and specificity targets. However, AVM induction of cytotoxicity through DNA damage is remains elusive. Here we investigate the cytotoxic effects of AVM in human nontarget cells in vitro. We clarify that AVM inhibited the viability of HeLa cells and enhanced apoptosis. We have used alkaline comet assay and gammaH2AX foci formation to detect DNA damage of HeLa cells. As expected, we found AVM caused DNA double-strand breaks in HeLa cells, as measured by significance of comet assay parameters (e.g., tail DNA) and increases of gammaH2AX foci in HeLa cells. Moreover, established assays of cytotoxicity were performed to characterize the mechanism of AVM toxicity on HeLa cells. The results demonstrated the collapse of mitochondrial membrane potential, and up-regulating the expression level of Bax/Bcl-2 resulted in a release of cytochrome c into cytosol as well as the activation of caspase-9/-3 and cleavage of poly(ADP-ribose) polymerase (PARP). We conclude that AVM has a potential risk to human health by inducing human cell DNA damage and mitochondria-associated apoptosis. PMID- 27551890 TI - More deaths from pancreatic cancer than breast cancer in the EU by 2017. AB - INTRODUCTION: Pancreatic cancer currently ranks below female breast cancer in terms of the number of deaths in both males and females in the EU. While breast cancer mortality rates have been declining in many higher income EU countries during recent decades, rates of pancreatic cancer in contrast are either stable or moderately increasing; a comparative analysis of the short-term future rates of both is warranted. METHODS: We extracted the annual number of deaths from cancers of the pancreas and breast by gender together with population at risk in each of 28 countries of the EU for the period 2001-2010. We fitted cancer- and gender-specific time-linear regression models and predicted deaths from pancreatic and breast cancer mortality for the years 2011-2025. RESULTS: We estimated that by the year 2017 more deaths from pancreatic cancer will occur (91 500 annual deaths) than breast cancer (91 000) in the EU. By 2025, deaths from cancer of the pancreas are predicted to be 25% higher (111 500 and 90 000, respectively). Pancreatic cancer may become the third leading cause of death from cancer in the EU after lung and colorectal cancers. CONCLUSION: Although strategies may emerge in the near future that will enhance the prospects of improving the very poor five-year survival from pancreatic cancer, coordinated efforts are necessary to reduce the foreseeable high mortality burden of disease within the EU. PMID- 27551891 TI - Novel Organophosphate Ligand O-(2-Fluoroethyl)-O-(p Nitrophenyl)Methylphosphonate: Synthesis, Hydrolytic Stability and Analysis of the Inhibition and Reactivation of Cholinesterases. AB - The organophosphate O-(2-fluoroethyl)-O-(p-nitrophenyl) methyphosphonate 1 is the first-in-class, fluorine-18 radiolabeled organophosphate inhibitor ([18F]1) of acetylcholinesterase (AChE). In rats, [18F]1 localizes in AChE rich regions of the brain and other tissues where it likely exists as the (CH3)(18FCH2CH2O)P(O) AChE adduct (ChE-1). Characterization of this adduct would define the inhibition mechanism and subsequent postinhibitory pathways and reactivation rates. To validate this adduct, the stability (hydrolysis) of 1 and ChE-1 reactivation rates were determined. Base hydrolysis of 1 yields p-nitrophenol and (CH3) (FCH2CH2O)P(O)OH with pseudo first order rate constants (kobsd) at pH 7.4 (PBS) of 3.25 * 10-4 min-1 (t1/2 = 35.5 h) at 25 degrees C and 8.70 * 10-4 min-1 (t1/2 = 13.3 h) at 37 degrees C. Compound 1 was a potent inhibitor of human acetylcholinesterase (HuAChE; ki = 7.5 * 105 M-1 min-1), electric eel acetylcholinesterase (EEAChE) (ki = 3.0 * 106 M-1 min-1), and human serum butyrylcholinesterase (HuBChE; 1.95 * 105 M-1 min-1). Spontaneous and oxime mediated reactivation rates for the (CH3) (FCH2CH2O)P(O)-serine ChE adducts using 2-PAM (10 MUM) were (a) HuAChE 8.8 * 10-5 min-1 (t1/2 = 131.2 h) and 2.41 * 10-2 min-1 (t1/2 = 0.48 h), (b) EEAChE 9.32 * 10-3 min-1 (t1/2 = 1.24 h) and 3.33 * 10 2 min-1 (t1/2 = 0.35 h), and (c) HuBChE 1.16 * 10-4 min-1 (t1/2 = 99.6 h) and 4.19 * 10-2 min-1 (t1/2 = 0.27 h). All ChE-1 adducts undergo rapid and near complete restoration of enzyme activity following addition of 2-PAM (30 min), and no aging was observed for either reactivation process. The fast reactivation rates and absence of aging of ChE-1 adducts are explained on the basis of the electron-withdrawing fluorine group that favors the nucleophilic reactivation processes but disfavors cation-based dealkylation aging mechanisms. Therefore, the likely fate of radiolabeled compound 1 in vivo is the formation of (CH3)(FCH2CH2O)P(O)-serine adducts and monoacid (CH3)(FCH2CH2O)P(O)OH from hydrolysis and reactivation. PMID- 27551892 TI - Bilateral adrenalectomy: a review of 10 years' experience. AB - INTRODUCTION The 2012 British Association of Endocrine and Thyroid Surgeons audit report showed that only 86 of 1359 patients who underwent adrenalectomy had a bilateral operation; thus the experience with this procedure remains limited. METHODS Retrospective review of patients undergoing bilateral adrenalectomy in a tertiary referral centre. RESULTS Between November 2005 and January 2016, bilateral adrenalectomy was performed in 23 patients (6 male, 17 female, age 43 +/- 4 years) diagnosed with Cushing's disease (n = 13), hereditary phaeochromocytomas (n = 6), adrenocortical cancer (n = 2), colorectal metastatic disease (n = 1) and adrenocortical adenomas (n = 1). A laparoscopic transperitoneal approach was used in 17 patients, with one conversion to open. Three patients had open adrenalectomies for adrenocortical cancer and for simultaneous phaeochromocytomas and pancreatic neuroendocrine tumours in a patient with Von Hippel-Lindau syndrome. Three patients with Cushing's had a bilateral retroperitoneoscopic operation. The mean operating time was 195 +/- 16 minutes for laparoscopic operations (n = 16), 243 +/- 44 minutes for open adrenalectomies (n = 4) and 151 +/- 12 minutes for retroperitoneal operations. It was significantly shorter for Cushing's disease than for phaeochromocytomas (162 +/- 8 vs. 257 +/- 39 minutes, P < 0.01). Median length of hospital stay was 5 days. Postoperative complications (Clavien-Dindo classification) included one chest infection (level 2), one postoperative haemorrhage and two chest drains for pneumothorax (level 3), two postoperative cardiac arrests (level 4) and one late cancer death from complications related to uncontrolled hypercortisolism (level 5). DISCUSSION Synchronous bilateral adrenalectomy remains an infrequent operation. The laparoscopic approach is feasible in the majority of patients. It is likely that the retroperitoneoscopic adrenalectomy will become the standard approach for bilateral operations. PMID- 27551893 TI - An emergency back-up light source for flexible cystoscopy can be found in most of our pockets. PMID- 27551894 TI - Trends in urgent referrals for suspected colorectal cancer: an increase in quantity, but not in quality. AB - INTRODUCTION An understanding of the volume of incoming referrals to a colorectal cancer (CRC) service is essential for adequate delivery of service. We hypothesised that the number of 2-week-wait (2WW) referrals has increased over recent years, with a concomitant increase in demand for endoscopic and imaging investigations. METHODS A retrospective review of all referrals from primary care with suspected malignancy to Barking, Havering and Redbridge NHS Trust (BHRNHST, London, UK) from 2009 to 2014 was undertaken. Annual numbers of CRC diagnoses, colonoscopies and CT scans among these patients were reviewed. Linear regression models were used to determine the significance of observed trends. RESULTS Annual number of 2WW referrals for all cancers increased steadily from 14,031 to 19,983 during the study period (p<0.01). Referrals for suspected CRC increased from 1,706 to 2,874 (p=0.02). Number of colonoscopies and CT scans carried out in 2WW patients also increased significantly. Proportion of patients referred as a 2WW diagnosed with CRC decreased from 7.9% in 2009 to 4.7% in 2014 (p=0.02). DISCUSSION Number of referrals for suspected cancer from primary care to BHRNHST is increasing steadily, which has implications for service provision. Prevalence of cancer diagnoses from these referrals is decreasing. CONCLUSIONS There has been a sustained and substantial increase in the number of urgent referrals for suspected CRC at BHRNHST over recent years, without an increase in the number of resulting cancer diagnoses. PMID- 27551895 TI - Endoscopic pilonidal abscess treatment: a novel approach for the treatment of pilonidal abscess. AB - INTRODUCTION Pilonidal abscess is a common surgical emergency. Conventional treatment with incision and drainage is associated with significant postoperative morbidity. We report our initial experience of using minimally invasive endoscopic technique for the treatment of pilonidal abscesses, referred to as endoscopic pilonidal abscess treatment (EPAT). MATERIALS AND METHODS A prospective database of all patients undergoing EPAT between January 2015 and March 2016 at Whiston Hospital was maintained. Data regarding patient demographics, peroperative variables and postoperative follow-up were recorded. RESULTS Nineteen patients were included, male to female ratio was 53 : 47 and median age of the cohort was 24 years (interquartile range 22-25 years). EPAT was the primary procedure for 10 patients and 9 had EPAT for recurrent pilonidal abscesses. There were no readmissions and none needed further surgery within 6 weeks of having the procedure. In all patients, complete wound healing was achieved within 6 weeks; all reported minimal postoperative pain (median postoperative visual analogue scale score 1) and immediate return to the activities of daily life. Four of the nineteen patients (21%) required definitive intervention for pilonidal disease in the follow-up period. CONCLUSIONS EPAT is a novel, minimally invasive technique for the treatment of acute pilonidal abscesses. It is safe, associated with reduced postoperative morbidity, recurrence rate and quick wound healing. Initial encouraging results require further investigations on a larger group of patients in a multicentre setting. PMID- 27551896 TI - The effect of surgical experience on the amount of radiation exposure from fluoroscopy during dynamic hip screw fixation. AB - INTRODUCTION Dynamic hip screw (DHS) fixation for proximal femur fractures is one of the most common procedures in trauma that requires the use of fluoroscopy. Emphasis is often placed on producing the 'perfect picture', which may lead to excessive use of fluoroscopy, without added patient benefit. This study, the largest of its kind, aimed to determine the effect of surgical experience on the amount of radiation exposure from fluoroscopy during DHS fixation. METHODS All hospital admissions for extracapsular proximal femur fractures to our institution between 2007 and 2012 were analysed. Patient demographics, fracture configuration, grade of surgeon and the total radiation dose after fixation were recorded. Analysis of variance was performed to assess differences in radiation levels between different grades of surgeon. RESULTS A total of 1,203 patients with a mean age of 81.3 years (range: 21-105 years) were included in the study. The majority of the fractures were three-part (33.3%), followed by two-part (32.2%), four-part (25.7%) and basicervical (8.9%). Registrars (ST3-ST8) used a significantly higher radiation dose than consultants for all fracture types (p=0.009). When analysed separately by trainee group, the most junior registrars (ST3-ST4) and the most senior registrars (ST7-ST8) were found to use significantly higher radiation levels than consultants (p=0.037 and p<0.001 respectively). CONCLUSIONS The level of surgical experience does influence the amount of radiation exposure from fluoroscopy during DHS fixation. Surgical trainees should not ignore the potential harmful effects of radiation and should be equipped with the knowledge of how to keep the radiation exposure as low as possible. PMID- 27551897 TI - Patterns, timing and consequences of post-thyroidectomy haemorrhage. AB - INTRODUCTION Post-thyroidectomy bleeding is a low frequency but potentially life threatening event that is very difficult to predict. Given the increasing drive towards thyroidectomy with same day discharge, this study was conducted with the aim of identifying patterns, timing and consequences of post-thyroidectomy bleeding to assess the feasibility of day-case thyroidectomy. METHODS All patients who underwent a thyroidectomy between 2008 and 2015 at our institution were identified. Patterns, timing and consequences in all those who developed post-thyroidectomy bleeding were studied. RESULTS Of the 805 patients included in the study, 14 required re-exploration for bleeding; 7 (50%) of these within 8 hours of surgery, 6 (43%) between 18 and 30 hours, and 1 (7%) at 49 hours. Just under half (43%) of those with post-thyroidectomy bleeding had thyrotoxicosis. CONCLUSIONS A significant number of postoperative haemorrhages occurred beyond the immediate postoperative period. Same day discharge after thyroidectomy cannot therefore be recommended as a routine practice. PMID- 27551898 TI - Penetrating foreign body in the masticator space with injury to the internal maxillary artery: a surgical challenge. AB - INTRODUCTION Foreign bodies (FBs) in the masticator space (MS) are a unique problem because of the difficulty of accessing this deep compartment within the head and neck. In addition, MS contents include critical structures such as the internal maxillary artery (IMA) and mandibular nerve. CASE HISTORY A 39-year-old tradesman was involved in a construction accident whereby a metallic projectile from a machinery drill penetrated his left cheek. Computed tomography revealed a metallic object of dimension 1.9 *1.2 cm within the MS, with concomitant fracture of left maxillary anterior and lateral walls. Surgery was indicated in view of constant pain and swelling. The FB was removed through the cheek laceration with the aid of an X-ray image intensifier. Persistent significant bleeding was observed within the wound cavity after FB removal that could not be arrested despite attempts at haemostasis with adrenaline packing and oxidised cellulose polymers. Urgent selective left external carotid angiography showed breach of a distal branch of the left internal maxillary artery with contrast extravasation. Embolisation of this branch was undertaken successfully with a liquid agent. CONCLUSIONS This is the first time a FB within the MS with injury to the internal maxillary artery has been described. PMID- 27551899 TI - Pyopericardium secondary to achalasia-associated squamous cell carcinoma of the oesophagus. AB - Patients with achalasia of the oesophagus are known to be at increased risk of oesophageal squamous cell carcinoma. To our knowledge, this is the first report of an achalasia-associated oesophageal squamous cell carcinoma presenting with acute sepsis secondary to pyopericardium. PMID- 27551900 TI - Appendiceal intussusception from endometriosis: endoscopic and laparoscopic approach. AB - Appendiceal intussusception is an rare diagnosis that may be found on imaging or at the time of surgery, as seen in this case of a 33-year-old female presenting with gastrointestinal symptoms. Images are presented with differential diagnosis as well as treatment options. PMID- 27551901 TI - Mantle cell lymphoma: primary oral presentation. AB - Mantle-cell lymphoma is an uncommon lymphoid malignancy of B-cells. It is often aggressive and prognosis is poor. A 69-year-old gentleman with a history of ischaemic heart disease was referred from primary care with a painless right floor of mouth swelling that had been present for 1 month. He otherwise completely asymptomatic. Incisional biopsy of the lesion was undertaken and marker studies demonstrated mantle cell lymphoma. Positron emission tomography computed tomography and bone marrow biopsy showed widespread but low volume involvement. The patient was referred to the haematology multidisciplinary team for further assessment and treatment. PMID- 27551902 TI - Deciduosis of the appendix: diagnostic dilemma continues despite MRI evidence. AB - Deciduosis (ectopic or extrauterine decidua) is a phenomenon seen in the ovary and cervix and on serosal surfaces of abdominal and pelvic organs. It is thought to be the result of progesterone effects on extrauterine mesenchymal cells during pregnancy. Although deposits are typically asymptomatic and incidentally found in surgically removed tissues on microscopy, deciduosis has also been known to cause pain and intraperitoneal haemorrhage. We sourced all cases of appendiceal deciduosis that have occurred in Sir Charles Gairdner Hospital and Bunbury Hospital between the years 2006 and 2014. Clinical information was obtained from patients' medical records. Four cases of ectopic decidua of the appendix, all of which were incidentally found in pregnant patients presenting with features highly suggestive of appendicitis, were reviewed. These patients underwent appendicectomy and subsequent histopathology findings showed deciduosis with no evidence of appendicitis. Deciduosis of the appendix can mimic acute appendicitis in pregnancy. At present, it is difficult to confidently differentiate one from the other either by way of clinical presentation or with current imaging modalities. PMID- 27551903 TI - A surgical approach in the management of mucormycosis in a trauma patient. AB - Mucormycosis as a consequence of trauma is a devastating complication; these infections are challenging to control, with a fatality rate approaching 96% in immunocompromised patients. We present a case where a proactive approach was successfully employed to treat mucormycosis following complex polytrauma. Aggressive repeated surgical debridement, in combination with appropriate antifungal therapy, proved successful in this instance. In our opinion, mucormycosis in trauma mandates an aggressive surgical approach. This prevents ascending dissemination of mucormycosis and certainly reduces the risk of patient mortality as a direct result. Anti-fungal therapy should be used secondarily as an adjunct together with surgical debridement, or as an alternative when surgical intervention is not feasible. PMID- 27551904 TI - A case of gastroduodenal lipomatosis. AB - Although sporadic lipomas are not uncommon in the upper gastrointestinal tract, diffuse gastroduodenal lipomatosis is a rare clinical entity. Medical literature reveals a limited number of such cases presenting with upper gastrointestinal obstruction or bleeding. We present the management experience of a 43-year-old woman who presented with intussusception causing high small-bowel obstruction secondary to jejunal lipomatosis. Computed tomography showed diffuse fatty thickening of the gastric wall in addition to multiple lipomas in stomach, duodenum and in the jejunum with jejunal intussusception. As complete resection of the affected segment was not possible, a side-to-side jejunal bypass was made. The patient remains well on review after 18 months. PMID- 27551905 TI - Vascular ring presenting as dysphagia in an adult woman: a case report. AB - A 48-year-old woman was seen in a surgical outpatient clinic with a 2 year history of progressive dysphagia with occasional regurgitation, partially controlled with a proton pump inhibitor. Primary investigations of pH testing and gastroscopy were normal, although a barium swallow study revealed significant hold-up at the aortic arch impression and a posterior right-sided oesophageal impression suggestive of a right-sided aortic arch. A follow-up computed tomography angiogram discovered a vascular ring encircling the trachea and oesophagus, formed by a right-sided aortic arch with aberrant aortic branches, and a Kommerell's diverticulum. It was deemed that the patient's symptoms were related to this vascular ring. The patient underwent stage-one surgery - an extra anatomic bypass of the double aortic arch and right subclavian artery - and 4 months later a stent graft insertion over the origin of the diverticulum with the aim of complete symptomatic relief. This case presents a common symptom familiar to any clinician (dysphagia), which has been caused by a rare pathology. It is even more unusual that this should present itself in adulthood. PMID- 27551906 TI - Perfoation of the gallbladder: 'bait' for the unsuspecting laparoscopic surgeon. AB - INTRODUCTION Cholecystectomy is one of the most common elective procedures carried out by general surgeons. Most patients present with typical biliary anatomy and simple gallstone disease. Intraoperative and postoperative courses are frequently predictable and uncomplicated. Nevertheless, a small but significant number of patients experience complicated disease with rare presentations and complex biliary anatomy. Unfortunately, consensus on appropriate care for such patients is lacking. CASE HISTORY We describe three patients who presented with complex manifestations of gallbladder perforation: acute perforation of the gallbladder; a spontaneous cholecystocutaneous fistula; a cholecystoduodenal fistula. The initial presentation, preoperative investigations, and selected surgical strategy for each case are described. CONCLUSIONS The case studies described here illustrate the need for a low index of suspicion for gallbladder perforation. Caution should be exercised in preoperative and intraoperative phases in this patient population. PMID- 27551907 TI - Selective Inhibition of MMP-2 Does Not Alter Neurological Recovery after Spinal Cord Injury. AB - Matrix metalloproteinase (MMP)-2 knockout (KO) mice show impaired neurological recovery after spinal cord injury (SCI), suggesting that this proteinase is critical to recovery processes. However, this finding in the KO has been confounded by a compensatory increase in MMP-9. We synthesized the thiirane mechanism-based inhibitor ND-378 and document that it is a potent (nanomolar) and selective slow-binding inhibitor of MMP-2 that does not inhibit the closely related MMP-9 and MMP-14. ND-378 crosses the blood-spinal cord barrier, achieving therapeutic concentrations in the injured spinal cord. Spinal-cord injured mice treated with ND-378 showed no change in long-term neurological outcomes, suggesting that MMP-2 is not a key determinant of locomotor recovery. PMID- 27551908 TI - Sulfoureido Lipopeptides from the Marine Sponge Discodermia kiiensis. AB - New N-sulfoureidylated lipopeptides, sulfolipodiscamides A-C (1-3), were isolated by gel filtration chromatography of the n-butanol fraction of the marine sponge Discodermia kiiensis. By extensive NMR analyses and high-resolution mass spectrometry, the structures of 1-3 were elucidated as having an unprecedented N sulfoureidyl group on the d-citrulline residue, a distinct feature that was not found in the structurally related lipodiscamides A-C (4-6), derived from the ether fraction of the same sponge. Furthermore, the absolute configurations of 1 3 were confirmed by comparisons of the HPLC retention times of the hydrolytic products and the corresponding authentic lipodiscamides. Interestingly, sulfolipodiscamide A displayed a 2.3-fold increase in cytotoxicity against murine leukemia (P388) cells, compared to the unconjugated parent compound. PMID- 27551909 TI - The fourth annual meeting of the American College of Professional Neuropsychology (ACPN) poster roster, March 9-10, 2012, Las Vegas, Nevada. PMID- 27551910 TI - Population genetic structure and molecular diversity of the red swamp crayfish in China based on mtDNA COI gene sequences. AB - Population genetic structure and molecular diversity are closely related to adaptability, potential and evolutionary of a species, which also reflects its population history. We analyzed the molecular variability and genetic structure among 24 populations of the red swamp crayfish in China based on the COI region. The COI of 687 bp aligned across 44 haplotypes, the average AT content (68.1%) was slightly higher than the AT content (31.9%). AMOVA indicated that a high proportion of the total genetic variance was attributable to variations within populations (87.57%), whereas only 12.43% occurred among populations. The Fst values were between 0.016 and 0.585, and the Nm values were between 0.178 and 15.182 in each population. All of the AMOVA, Fst statistics and Nm values suggested low genetic differentiation, but a high level genetic diversity existed in Chinese populations of Procambarus clarkii. The phylogenetic trees showed that some geographical populations were irregularly distributed according to the river systems while others were matched well, suggesting that genetic differentiation is created largely by geographic isolation. PMID- 27551911 TI - Reply letter and clarifications on behalf of La Rosa and colleagues to Sicilian Public Health Authorities. AB - In May 2016 we published in the journal Human Vaccines and Immunotherapy. 1 79 80 the case-report "Post-rotavirus vaccine intussusception in identical twins: a case report." We received a reply letter from "Sicilian Public Health Authorities" that placed attention to some points of our work. We would like to do some clarifications. PMID- 27551912 TI - "It just took the pressure off": The voices of Veterans' family caregivers in a participant-directed program. AB - The Veteran-Directed Home and Community Based Services Program (VD-HCBS) operates using a participant-direction approach, allowing Veterans to self-direct services. Only a small body of literature has explored the impact of these programs on caregivers. This study aimed to explore the experiences of caregivers in VD-HCBS. Telephone focus groups and interviews were conducted with caregivers (n = 23; 52.2% spouses; 8.7% male). Conventional content analysis revealed five categories: Coming home and staying home; Taking the pressure off; Providing security; Giving us time as a couple; and Importance of choice. Stories highlighted sources of stress and mechanisms behind stress relief and support. PMID- 27551913 TI - A meta-analysis of the variables related to job satisfaction among Korean nurses. AB - BACKGROUND: The shortage of nursing workforce has been a critical and global issue and associated with job satisfaction. OBJECTIVES: To evaluate the strength of the relationships between job satisfaction and organizational commitment, job stress, and turnover intention among Korean nurses. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; Korean Education & Research Information Service, KISS, DB pia, PubMed, and CINAHL databases were searched. The meta-analysis software package, R program (version 3.0.1), was used. RESULTS: Thirty-eight of 1245 screened studies had appropriate data. The overall relationships were high and significant, and increased organizational commitment (WES = .62), decreased turnover intention (WES = -.47), and decreased job stress (WES = -.37) were associated with job satisfaction. CONCLUSION: The strongest relationship was identified between organizational commitment and job satisfaction. These findings have important implications for improving organizational commitment to increase job satisfaction among nurses. PMID- 27551914 TI - When Breath Becomes Air. PMID- 27551915 TI - Discovery of a Family of Genomic Sequences Which Interact Specifically with the c MYC Promoter to Regulate c-MYC Expression. AB - G-quadruplex forming sequences are particularly enriched in the promoter regions of eukaryotic genes, especially of oncogenes. One of the most well studied G quadruplex forming sequences is located in the nuclease hypersensitive element (NHE) III1 of the c-MYC promoter region. The oncoprotein c-MYC regulates a large array of genes which play important roles in growth regulation and metabolism. It is dysregulated in >70% of human cancers. The silencer NHEIII1 located upstream of the P1 promoter regulates up-to 80% of c-MYC transcription and includes a G quadruplex structure (Pu27) that is required for promoter inhibition. We have identified, for the first time, a family of seventeen G-quadruplex-forming motifs with >90% identity with Pu27, located on different chromosomes throughout the human genome, some found near or within genes involved in stem cell maintenance or neural cell development. Notably, all members of the Pu27 family interact specifically with NHEIII1 sequence, in vitro. Crosslinking studies demonstrate that Pu27 oligonucleotide binds specifically to the C-rich strand of the NHEIII1 resulting in the G-quadruplex structure stabilization. Pu27 homologous sequences (Pu27-HS) significantly inhibit leukemic cell lines proliferation in culture. Exposure of U937 cells to the Pu27-HS induces cell growth inhibition associated with cell cycle arrest that is most likely due to downregulation of c-MYC expression at the RNA and/or protein levels. Expression of SOX2, another gene containing a Pu27-HS, was affected by Pu27-HS treatment as well. Our data suggest that the oligonucleotides encoding the Pu27 family target complementary DNA sequences in the genome, including those of the c-MYC and SOX2 promoters. This effect is most likely cell type and cell growth condition dependent. The presence of genomic G-quadruplex-forming sequences homologous to Pu27 of c-MYC silencer and the fact that they interact specifically with the parent sequence suggest a common regulatory mechanism for genes whose promoters contain these sequences. PMID- 27551916 TI - Transsacral-Transiliac Screw Stabilization: Effective for Recalcitrant Pain Due to Sacral Insufficiency Fracture. AB - OBJECTIVES: To evaluate the effectiveness of transsacral-transiliac screw fixation for the treatment of sacral insufficiency fractures that fail nonoperative treatment. DESIGN: A pilot study series of consecutive patients identified over 5 years were treated and followed prospectively. SETTING: Academic-affiliated, tertiary referral, level 1 trauma center in Dallas, TX. PATIENTS/PARTICIPANTS: Patients were selected on the basis of presenting diagnosis, and failure of nonoperative treatment of their sacral insufficiency fracture. Eleven patients entered to the study, and 10 completed follow-up. INTERVENTION: Placement of transsacral-transiliac screws for sacral insufficiency fracture. MAIN OUTCOME MEASUREMENTS: Comparison of preoperative and postoperative Visual Analog Scale scores and Oswestry Low Back Disability Index scores. RESULTS: Patients experienced statistically significant improvement in both outcome measures after intervention. No complications encountered. CONCLUSIONS: Transsacral-transiliac screw fixation seems to be a safe and effective treatment for sacral insufficiency fractures recalcitrant to nonoperative management. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27551917 TI - Availability and Use of HIV Monitoring and Early Infant Diagnosis Technologies in WHO Member States in 2011-2013: Analysis of Annual Surveys at the Facility Level. AB - BACKGROUND: The Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets have reinforced the importance of functioning laboratory services to ensure prompt diagnosis and to assess treatment efficacy. We surveyed the availability and utilization of technologies for HIV treatment monitoring and early infant diagnosis (EID) in World Health Organization (WHO) Member States. METHODS AND FINDINGS: The survey questionnaire included 14 structured questions focusing on HIV testing, cluster of differentiation 4 (CD4) testing, HIV viral load (VL) testing, and EID and was administered annually from 2012 to 2014 through WHO country offices, with each survey covering the previous 12-mo period. Across 127 targeted countries, survey response rates were 60% in 2012, 67% in 2013, and 78% in 2014. There were encouraging trends towards increased procurement of CD4 and VL/EID instruments in reporting countries. Globally, the capacity of available CD4 instruments was sufficient to meet the demand of all people living with HIV/AIDS (PLWHA), irrespective of treatment status (4.62 theoretical tests per PLWHA in 2013 [median 7.33; interquartile range (IQR) 3.44 17.75; median absolute deviation (MAD) 4.35]). The capacity of VL instruments was inadequate to cover all PLWHA in many reporting countries (0.44 tests per PLWHA in 2013 [median 0.90; IQR 0.30-2.40; MAD 0.74]). Of concern, only 13.7% of existing CD4 capacity (median 4.3%; IQR 1.1%-12.1%; MAD 3.8%) and only 36.5% of existing VL capacity (median 9.4%; IQR 2.3%-28.9%; MAD 8.2%) was being utilized across reporting countries in 2013. By the end of 2013, 7.4% of all CD4 instruments (5.8% CD4 conventional instruments and 11.0% of CD4 point of care [POC]) and 10% of VL/EID instruments were reportedly not in use because of lack of reagents, the equipment not being installed or deployed, maintenance, and staff training requirements. Major limitations of this survey included under reporting and/or incomplete reporting in some national programmes and noncoverage of the private sector. CONCLUSION: This is the first attempt to comprehensively gather information on HIV testing technology coverage in WHO Member States. The survey results suggest that major operational changes will need to be implemented, particularly in low- and middle-income countries, if the 90-90-90 targets are to be met. PMID- 27551919 TI - Environmental DNA Marker Development with Sparse Biological Information: A Case Study on Opossum Shrimp (Mysis diluviana). AB - The spread of Mysis diluviana, a small glacial relict crustacean, outside its native range has led to unintended shifts in the composition of native fish communities throughout western North America. As a result, biologists seek accurate methods of determining the presence of M. diluviana, especially at low densities or during the initial stages of an invasion. Environmental DNA (eDNA) provides one solution for detecting M. diluviana, but building eDNA markers that are both sensitive and species-specific is challenging when the distribution and taxonomy of closely related non-target taxa are poorly understood, published genetic data are sparse, and tissue samples are difficult to obtain. To address these issues, we developed a pair of independent eDNA markers to increase the likelihood of a positive detection of M. diluviana when present and reduce the probability of false positive detections from closely related non-target species. Because tissue samples of closely-related and possibly sympatric, non-target taxa could not be obtained, we used synthetic DNA sequences of closely related non target species to test the specificity of eDNA markers. Both eDNA markers yielded positive detections from five waterbodies where M. diluviana was known to be present, and no detections in five others where this species was thought to be absent. Daytime samples from varying depths in one waterbody occupied by M. diluviana demonstrated that samples near the lake bottom produced 5 to more than 300 times as many eDNA copies as samples taken at other depths, but all samples tested positive regardless of depth. PMID- 27551918 TI - Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan. AB - Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations. PMID- 27551920 TI - Impact of Commercial Strain Use on Saccharomyces cerevisiae Population Structure and Dynamics in Pinot Noir Vineyards and Spontaneous Fermentations of a Canadian Winery. AB - Wine is produced by one of two methods: inoculated fermentation, where a commercially-produced, single Saccharomyces cerevisiae (S. cerevisiae) yeast strain is used; or the traditional spontaneous fermentation, where yeast present on grape and winery surfaces carry out the fermentative process. Spontaneous fermentations are characterized by a diverse succession of yeast, ending with one or multiple strains of S. cerevisiae dominating the fermentation. In wineries using both fermentation methods, commercial strains may dominate spontaneous fermentations. We elucidate the impact of the winery environment and commercial strain use on S. cerevisiae population structure in spontaneous fermentations over two vintages by comparing S. cerevisiae populations in aseptically fermented grapes from a Canadian Pinot Noir vineyard to S. cerevisiae populations in winery conducted fermentations of grapes from the same vineyard. We also characterize the vineyard-associated S. cerevisiae populations in two other geographically separate Pinot Noir vineyards farmed by the same winery. Winery fermentations were not dominated by commercial strains, but by a diverse number of strains with genotypes similar to commercial strains, suggesting that a population of S. cerevisiae derived from commercial strains is resident in the winery. Commercial and commercial-related yeast were also identified in the three vineyards examined, although at a lower frequency. There is low genetic differentiation and S. cerevisiae population structure between vineyards and between the vineyard and winery that persisted over both vintages, indicating commercial yeast are a driver of S. cerevisiae population structure. We also have evidence of distinct and persistent populations of winery and vineyard-associated S. cerevisiae populations unrelated to commercial strains. This study is the first to characterize S. cerevisiae populations in Canadian vineyards. PMID- 27551921 TI - Irreversibility of T-Cell Specification: Insights from Computational Modelling of a Minimal Network Architecture. AB - BACKGROUND/OBJECTIVES: A cascade of gene activations under the control of Notch signalling is required during T-cell specification, when T-cell precursors gradually lose the potential to undertake other fates and become fully committed to the T-cell lineage. We elucidate how the gene/protein dynamics for a core transcriptional module governs this important process by computational means. METHODS: We first assembled existing knowledge about transcription factors known to be important for T-cell specification to form a minimal core module consisting of TCF-1, GATA-3, BCL11B, and PU.1 aiming at dynamical modeling. Model architecture was based on published experimental measurements of the effects on each factor when each of the others is perturbed. While several studies provided gene expression measurements at different stages of T-cell development, pure time series are not available, thus precluding a straightforward study of the dynamical interactions among these genes. We therefore translate stage dependent data into time series. A feed-forward motif with multiple positive feed-backs can account for the observed delay between BCL11B versus TCF-1 and GATA-3 activation by Notch signalling. With a novel computational approach, all 32 possible interactions among Notch signalling, TCF-1, and GATA-3 are explored by translating combinatorial logic expressions into differential equations for BCL11B production rate. RESULTS: Our analysis reveals that only 3 of 32 possible configurations, where GATA-3 works as a dimer, are able to explain not only the time delay, but very importantly, also give rise to irreversibility. The winning models explain the data within the 95% confidence region and are consistent with regard to decay rates. CONCLUSIONS: This first generation model for early T-cell specification has relatively few players. Yet it explains the gradual transition into a committed state with no return. Encoding logics in a rate equation setting allows determination of binding properties beyond what is possible in a Boolean network. PMID- 27551922 TI - Place of Death in Patients with Lung Cancer: A Retrospective Cohort Study from 2004-2013. AB - INTRODUCTION: Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. METHODS AND FINDINGS: We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. RESULTS: Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. CONCLUSIONS: A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access. PMID- 27551923 TI - Obesity and anthropometry in spina bifida: What is the best measure. AB - OBJECTIVE: Diagnosis of obesity using traditional body mass index (BMI) using length may not be a reliable indicator of body composition in spina bifida (SB). We examine traditional and surrogate measures of adiposity in adults with SB, correlated with activity, metabolic disease, attitudes towards exercise and quality of life. DESIGN: Adult subjects with SB underwent obesity classification using BMI by length and arm span, abdominal girth and percent trunk fat (TF) on dual energy X-ray absorptiometry (DXA). Quality of life measures, activity level and metabolic laboratory values were also reviewed. RESULTS: Among eighteen subjects (6 male, 12 female), median age was 26.5 (range 19-37) years, with level of lesion 16.7% <=L2, 61.1% L3-4, and 22.2% >=L5, respectively. Median weight was 71.8 (IQR 62.4, 85.8) kg, similar between sexes (P = 0.66). With median length of 152.0 (IQR 141.8, 163.3) cm, median conventional BMI was 29.4 m/kg2, with 7 (43.8%) subjects with BMI >30. Median BMI by arm span was 30.2 m/kg2, abdominal girth of 105.5 cm, and TF 45.7%. More subjects were classified as obese using alternate measures, with 9 (56.3%) by arm span, 14 (82.4%) by abdominal girth and 15 (83.3%) by TF (P = 0.008). Reclassification of obesity from conventional BMI was significant when using TF (P = 0.03). No difference in quality of life measures, activity level and metabolic abnormalities was demonstrated between obese and non-obese subjects. CONCLUSIONS: Conventional determination of obesity using BMI by length is an insensitive marker in adults with SB. Adults with SB are more often classified as obese using TF by DXA. PMID- 27551924 TI - Ocean Acidification Effects on Atlantic Cod Larval Survival and Recruitment to the Fished Population. AB - How fisheries will be impacted by climate change is far from understood. While some fish populations may be able to escape global warming via range shifts, they cannot escape ocean acidification (OA), an inevitable consequence of the dissolution of anthropogenic carbon dioxide (CO2) emissions in marine waters. How ocean acidification affects population dynamics of commercially important fish species is critical for adapting management practices of exploited fish populations. Ocean acidification has been shown to impair fish larvae's sensory abilities, affect the morphology of otoliths, cause tissue damage and cause behavioural changes. Here, we obtain first experimental mortality estimates for Atlantic cod larvae under OA and incorporate these effects into recruitment models. End-of-century levels of ocean acidification (~1100 MUatm according to the IPCC RCP 8.5) resulted in a doubling of daily mortality rates compared to present-day CO2 concentrations during the first 25 days post hatching (dph), a critical phase for population recruitment. These results were consistent under different feeding regimes, stocking densities and in two cod populations (Western Baltic and Barents Sea stock). When mortality data were included into Ricker-type stock-recruitment models, recruitment was reduced to an average of 8 and 24% of current recruitment for the two populations, respectively. Our results highlight the importance of including vulnerable early life stages when addressing effects of climate change on fish stocks. PMID- 27551925 TI - International consensus conference on open abdomen in trauma. AB - BACKGROUND: A part of damage-control laparotomy is to leave the fascial edges and the skin open to avoid abdominal compartment syndrome and allow further explorations. This condition, known as open abdomen (OA), although effective, is associated with severe complications. Our aim was to develop evidence-based recommendations to define indications for OA, techniques for temporary abdominal closure, management of enteric fistulas, and methods of definitive wall closure. METHODS: The literature from 1990 to 2014 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-analyses] protocol. Seventy-six articles were reviewed by a panel of experts to assign grade of recommendations (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] system, and an international consensus conference was held. RESULTS: OA in trauma is indicated at the end of damage-control laparotomy, in the presence of visceral swelling, for a second look in vascular injuries or gross contamination, in the case of abdominal wall loss, and if medical treatment of abdominal compartment syndrome has failed (GoR B, LoE II). Negative-pressure wound therapy is the recommended temporary abdominal closure technique to drain peritoneal fluid, improve nursing, and prevent fascial retraction (GoR B, LoE I). Lack of OA closure within 8 days (GoR C, LoE II), bowel injuries, high-volume replacement, and use of polypropylene mesh over the bowel (GoR C, LoE I) are risk factors for frozen abdomen and fistula formation. Negative-pressure wound therapy allows to isolate the fistula and protect the surrounding tissues from spillage until granulation (GoR C, LoE II). Correction of fistula is performed after 6 months to 12 months. Definitive closure of OA has to be obtained early (GoR C, LoE I) with direct suture, traction devices, component separation with or without mesh. Biologic meshes are an option for wall reinforcement if bacterial contamination is present (GoR C, LoE II). CONCLUSION: OA and negative-pressure techniques improve the care of trauma patients, but closure must be achieved early to avoid complications. PMID- 27551926 TI - Compliance Patterns and Utilization of e-Health for Glucose Monitoring: Standalone Internet Gateway and Tablet Device. AB - BACKGROUND: Knowledge regarding compliance patterns and service utilization in e health is important for the development of effective services. To develop proper e-health, the characteristics of compliance patterns and utilization of e-health should be studied. We studied these for glucose monitoring of diabetic patients from primary clinics. MATERIALS AND METHODS: Data were collected from 160 outpatients who participated in e-health for glucose monitoring funded by the Korean government. Specifically, this study focused on two device types: a standalone Internet gateway and a tablet device. The SPSS 18.0 software was used for statistical analyses of demographic characteristics, survival data, and Cox proportional hazards regression model. RESULTS: Standalone Internet gateway users demonstrated a more stable compliance pattern than did tablet device users. The compliance rate differed according to the device type. Typically, compliance decreases considerably around 8 months. In these results, standalone Internet gateway users utilized the service for longer periods than tablet device users. Gateway type and location also influenced utilization (p < 0.05). CONCLUSIONS: The service should be designed according to the device type to develop appropriate service models. Thus, service designers should understand the different characteristics of service devices. This study provides insight into compliance patterns and utilization to develop appropriate service models and service interventions depending on the device. PMID- 27551928 TI - Optical Coherence Tomography and Biometry in High Myopia with Tilted Disc. AB - PURPOSE: The purpose of this study was to compare retinal thickness and biometric parameters between highly myopic eyes with and without tilted optic discs. METHODS: A total of 60 eyes from 60 highly myopic individuals (defined as a mean spherical equivalent refraction of -6.00 D or greater and axial length >=26 mm) underwent detailed ophthalmic examination. Twenty-one eyes (13 females and 8 males; mean age: 29 +/- 7 years) with tilted optic discs were recruited and compared with 39 eyes (23 females and 16 males; mean age: 28 +/- 6 years) of control subjects without tilted optic discs using spectral domain optical coherence tomography (OCT) and the Lenstar biometer. Disc ovality was assessed using the ratio of minimum to maximum disc diameter (index of tilt). A ratio of <=0.80 was considered as a tilted optic disc. RESULTS: There were no significant differences in biometric parameters between two groups. However, myopia in the tilted disc group was significantly greater compared to the non-tilted group ( 8.82 +/- 1.58 D vs. -7.84 +/- 1.22 D, p = 0.01). Comparison of OCT sectoral macular nerve fiber layer measurements between groups showed significant differences in inner ring thicknesses for the nasal (p = 0.01), inferior (p < 0.001), and temporal (p = 0.04) quadrants. A significant difference was also seen in outer ring macular nerve fiber layer thickness for the temporal quadrant (p = 0.03). No significant differences were demonstrated in optic disc peripapillary retinal nerve fiber layer (RNFL) thickness between the two groups. CONCLUSIONS: Mean spherical equivalent refractive error is strongly correlated with optic disc tilt; however, other biometric factors are independent of tilt. Structural examination of the eye using OCT can be employed to differentiate between eyes with tilted optic discs and those with normal discs. Peripapillary RNFL appears to be unaffected by tilted discs. PMID- 27551927 TI - Concomitant atrial fibrillation surgery for people undergoing cardiac surgery. AB - BACKGROUND: People with atrial fibrillation (AF) often undergo cardiac surgery for other underlying reasons and are frequently offered concomitant AF surgery to reduce the frequency of short- and long-term AF and improve short- and long-term outcomes. OBJECTIVES: To assess the effects of concomitant AF surgery among people with AF who are undergoing cardiac surgery on short-term and long-term (12 months or greater) health-related outcomes, health-related quality of life, and costs. SEARCH METHODS: Starting from the year when the first "maze" AF surgery was reported (1987), we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (March 2016), MEDLINE Ovid (March 2016), Embase Ovid (March 2016), Web of Science (March 2016), the Database of Abstracts of Reviews of Effects (DARE, April 2015), and Health Technology Assessment Database (HTA, March 2016). We searched trial registers in April 2016. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of any concomitant AF surgery compared with no AF surgery among adults with preoperative AF, regardless of symptoms, who were undergoing cardiac surgery for another indication. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We evaluated the risk of bias using the Cochrane 'Risk of bias' tool. We included outcome data on all-cause and cardiovascular-specific mortality, freedom from atrial fibrillation, flutter, or tachycardia off antiarrhythmic medications, as measured by patient electrocardiographic monitoring greater than three months after the procedure, procedural safety, 30-day rehospitalisation, need for post discharge direct current cardioversion, health-related quality of life, and direct costs. We calculated risk ratios (RR) for dichotomous data with 95% confidence intervals (CI) using a fixed-effect model when heterogeneity was low (I2 <= 50%) and random-effects model when heterogeneity was high (I2 > 50%). We evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to create a 'Summary of findings' table. MAIN RESULTS: We found 34 reports of 22 trials (1899 participants) with five additional ongoing studies and three studies awaiting classification. All included studies were assessed as having high risk of bias across at least one domain. The effect of concomitant AF surgery on all-cause mortality was uncertain when compared with no concomitant AF surgery (7.0% versus 6.6%, RR 1.14, 95% CI 0.81 to 1.59, I2 = 0%, 20 trials, 1829 participants, low quality evidence), but the intervention increased freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off antiarrhythmic medications > three months (51.0% versus 24.1%, RR 2.04, 95% CI 1.63 to 2.55, I2 = 0%, eight trials, 649 participants, moderate-quality evidence). The effect of concomitant AF surgery on 30-day mortality was uncertain (2.3% versus 3.1%, RR 1.25 95% CI 0.71 to 2.20, I2 = 0%, 18 trials, 1566 participants, low-quality evidence), but the intervention increased the risk of permanent pacemaker implantation (6.0% versus 4.1%, RR 1.69, 95% CI 1.12 to 2.54, I2 = 0%, 18 trials, 1726 participants, moderate-quality evidence). Investigator-defined adverse events, including but limited to, need for surgical re-exploration or mediastinitis, were not routinely reported but were not different between the two groups (other adverse events: 24.8% versus 23.6%, RR 1.07, 95% CI 0.85 to 1.34, I2 = 45%, nine trials, 858 participants), but the quality of this evidence was very low. AUTHORS' CONCLUSIONS: For patients with AF undergoing cardiac surgery, there is moderate-quality evidence that concomitant AF surgery approximately doubles the risk of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs while increasing the risk of permanent pacemaker implantation. The effects on mortality are uncertain. Future, high quality and adequately powered trials will likely affect the confidence on the effect estimates of AF surgery on clinical outcomes. PMID- 27551929 TI - Effects of Cold Ischemia on Gene Expression: A Review and Commentary. AB - Frequently investigators request that tissues be collected and processed in less than one hour following removal from a patient. Some biorepositories expend significant personnel time and other resources in trying to meet such goals; however, it is unclear whether the perceived benefits of relatively short cold ischemia times warrant these added costs. The literature of human surgical tissues prospectively exposed to cold ischemia at several time points was reviewed to compare the changes in transcripts/genes and microRNA with time of cold ischemia. Also, reports of protein changes in response to cold ischemia were correlated to changes in genes. The literature is limited; however, for most tissues, only a small proportion of transcripts/genes (<1%) changes up to 3 hours following surgery and most transcripts increase rather than decrease in less than 2 hours of cold ischemia. Biorepositories and investigators must consider the literature for evidence of significant changes in molecular results from tissues before spending significant resources on relatively rapid collection of tissues to meet cold ischemia times of less than 3 hours. Instead, those using human tissues in research must consider if the cold ischemia times affect their use in specific research; hence are these tissues "fit for purpose?" PMID- 27551930 TI - Modified Rapid AChE Method (MRAM) for Hirschsprung Disease Diagnosis: A Journey from Meier-Ruge Until Now. AB - Hirschsprung disease (HSCR) can be diagnosed using a variety of histological and immunohistochemical methods and stains. Because of the nature of the condition and the need for a rapid diagnostic confirmation, those methods with high accuracy and fast turnaround times are preferred. The authors of this paper have used rapid acetylcholinesterase (AChE) immunohistochemistry in conjunction with standard H&E in order to optimize diagnostic accuracy, and present a modified rapid AChE method (MRAM) that has been successfully utilized for over 20 years. The authors also present a list of over 30 different methods and stains that have been proposed for Hirschsprung disease diagnosis. PMID- 27551931 TI - Stereoselective and Versatile Preparation of Tri- and Tetrasubstituted Allylic Amine Scaffolds under Mild Conditions. AB - Significant progress has been observed in recent years in the synthesis of allylic amines, which are important building blocks in synthetic chemistry. Most of these processes are effective toward the preparation of allylic amines, with limited potential to introduce three or four different substituents on the olefinic unit in a stereocontrolled fashion. Therefore, the discovery of a mild and operationally simple protocol allowing such challenging stereoselective synthesis of multisubstituted allylic amines remains an inspiring target. Herein, we report the first general and practical methodology for the stereoselective synthesis of tri- and tetrasubstituted allylic amines based on Pd-catalyzed conversion of allyl surrogates readily obtained from cyclic vinyl carbonates. These rare conversions are characterized by excellent stereoselectivity, operational simplicity, mild reaction conditions, and wide scope in reaction partners. DFT studies were performed to rationalize the stereocontrol in these allylic amine formation reactions, and evidence is provided that the formation of a six-membered palladacyclic intermediate leads toward the formation of (Z) configured allylic amine products. PMID- 27551933 TI - The multiple biological action potential of melatonin - is melatonin, mitochondria and the ischemic/reperfusion injury relationship essential in the pathogenesis of obstructive nephropathy? PMID- 27551932 TI - Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells. AB - Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1DeltaT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either anti CD3/CD28 or Concanavalin A, but, as predicted, were completely unresponsive to IL 1beta administration. Furthermore, IL-1R1DeltaT mice were protected from gut inflammation in the anti-CD3 treatment model, due to dramatically reduced frequencies and absolute numbers of IL-17A and interferon (IFN)-gamma producing cells. Taken together, our data shows the necessity of intact IL-1 signaling for survival and expansion of CD4 T cells that were developed in an otherwise IL-1 sufficient environment. PMID- 27551935 TI - Assessment of Gait Symmetry Improvements in National Athletes after Anterior Cruciate Ligament Reconstruction during Rehabilitation. AB - This study aimed to quantify changes in gait parameters and their symmetries among athletes with anterior cruciate ligament (ACL) reconstructions during a rehabilitation program. Twenty-two national players with ACL reconstructions and 15 healthy athletes were recruited. The gait data were collected between postoperative weeks 4-5, 8-9 and 12-13 using a three-dimensional motion analysis system. The spatio-temporal gait parameters and symmetry indexes (SIs) were evaluated for the patients and the control group. One-way and repeated-measures multivariate analysis of variance were used to analyse the data. The results demonstrated significant differences among spatio-temporal (P<0.001) and SIs (P=0.007) of patients for Test 1 and the control group. Repeated measure analysis revealed significant changes in the linear combinations of spatio-temporal gait variables (P=0.002) and SIs (P=0.043) over time. The injured limb's step length, cadence and weight acceptance time presented significant improvement across time (P<0.001). Moreover, the SI of the stance time was reduced significantly by 46.48% (P=0.004) among SI parameters. After three months, no significant differences were found between patients and healthy controls for the measured gait components (P>0.05). The rehabilitation program allowed national athletes to restore symmetry in spatio-temporal gait parameters toward the control group's range 12-13 weeks post-reconstruction. PMID- 27551934 TI - Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex. AB - Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep-wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans. PMID- 27551936 TI - Kicking Velocity and Effect on Match Performance When using a Smaller, Lighter Ball in Women's Football. AB - The present study evaluated the effect of a smaller, lighter ball on kicking speed and technical-tactical and physical match performance in high-level adult female footballers. In the laboratory test setting, the peak ball velocity was 6% higher with the new ball (NB) than the standard ball (SB) (26.5+/-0.5 vs. 25.1+/ 0.5 m.s-1, p<0.05). However, during match-play, no differences were observed in mean heart rate (87+/-5 vs. 87+/-5%HRmax; p>0.05), blood lactate (90 min: 4.7+/ 1.7 and 4.0+/-1.7 mmol.l-1; p>0.05), total distance covered (10.6+/-0.9 and 10.4+/-0.8 km; p>0.05), intense running (>16 km/h) (2.08+/-0.42 and 1.94+/-0.38 km; p>0.05) and match-induced decrement in Yo-Yo IR1 performance (28 vs. 31%, respectively, p<0.05) using NB compared to SB. Likewise, no difference was observed in the number of short, medium-range or long passes during matches played with the 2 ball types, and there was no difference in passing success rate (NB: 68+/-1% and SB: 68+/-1%, p>0.05). In conclusion, high-level adult female footballers had a higher kicking speed when using a smaller, lighter ball, but no differences were observed during match-play with the 2 ball types in respect of technical-tactical and physical match performance. The physical loading was high for the players when playing with both ball types. PMID- 27551937 TI - Acute Hypotensive Response to Continuous and Accumulated Isocaloric Aerobic Bouts. AB - Evidence indicates that chronic reductions in blood pressure (BP) due to aerobic exercise depend on the ability to induce post-exercise hypotension (PEH) after each training bout. The purpose of this study was to investigate PEH after isocaloric bouts of continuous and accumulated running. 10 healthy pre hypertensive men (aged 27.6+/-3.5 years) performed the following bouts of exercise: a) A continuous bout (CONT) expending a total of 400 kcal; and b) An accumulated bout split into 2*200 kcal (INTER1 and INTER2) to total 400 kcal at 75% of oxygen uptake reserve. BP, mean arterial pressure (MAP) and heart rate variability were monitored 10 min before and 60 min after control and all exercise conditions. The decrease in MAP over time after continuous (400 kcal) and accumulated (2*200 kcal) bouts of exercise was more pronounced than during control (mean diff between 1.6 and 5.4 mmHg, P<=0.01), although the magnitude of change was similar between continuous and accumulated bouts (mean diff=0.1 mmHg, P=0.79). Concomitant to the PEH, sympathovagal balance was inversely related to changes in MAP after isocaloric bouts performed continuously and cumulatively (r= 0.72 and-0.85, P=0.019 and 0.002, respectively). In conclusion, BP decreased to similar levels after continuous and accumulated acute aerobic exercise matched for total energy expenditure. Our findings also indicate that the recovery pattern of cardiac autonomic activity may have an important role in eliciting PEH. PMID- 27551938 TI - Absence of Bilateral Differences in Child Baseball Players with Throwing-related Pain. AB - The aim of this study was to assess whether side-to-side differences in morphology and function of the upper limbs in 11-12 year-old male baseball players with throwing-related pain (n=14) were more pronounced than that of age matched healthy untrained subjects (n=16). Baseball players 1) had played baseball>=4.5 h.wk-1 for >= 4 years and (2) suffered from moderate-intensity (3-6 points on 10-point questionnaire scale) throwing-related pain in the shoulder or elbow in at least 2 training sessions within the past month. The range of motion (ROM), function and structure of the elbows and shoulders were assessed using goniometry, isokinetic dynamometry and ultrasonography. While the ROM and eccentric external peak torque of internal shoulder rotation were lower, the thickness of the supraspinatus tendon, the ulnar collateral ligament and articular cartilage of the humeral head were larger in baseball players than controls. There were, however, no significant side-to-side differences in any parameter in either group. In conclusion, it is unlikely that side-to-side differences in shoulder and upper limb structure and function contributed to the throwing-related pain in young baseball players, but low shoulder eccentric external peak torque and range of internal rotation may predispose to throwing related pain. PMID- 27551939 TI - High-intensity Interval Training in the Boundaries of the Severe Domain: Effects on Sprint and Endurance Performance. AB - In order to compare the effects of two 4-week interval training programs performed at the lower (Critical Power, CP) or at the higher (The highest intensity at which VO2max is attained, IHIGH) intensities of the severe exercise domain on sprint and endurance cycling performance, 21 recreationally trained cyclists performed the Wingate Anaerobic Test (WAnT) and a 250-kJ time trial. Accumulated oxygen deficit (AOD), surface electromyography (RMS), and blood lactate kinetics were measured during the WAnT. Subjects were assigned to 105% CP or IHIGH groups. During the WAnT, significantly greater improvements in peak (Mean +/-95%CI) (5.7+/-2.3% vs. 0.2+/-2.2%), mean power output (MPO) (3.7+/-2.0% vs. 0.5+/-1.8%), and RMS (17.8+/-7.4% vs. -15.7+/-7.9%) were observed in the IHIGH group (P<0.05). Higher and lower AOD, respectively, at the start and during the second half of the WAnT were observed after IHIGH training. The changes in RMS and MPO induced by the training were significantly correlated (r=0.584). The 2 interventions induced improvements in the 250-kJ time trial. In conclusion, although the improvements in endurance performance were similar, training at IHIGH led to higher gains in WAnT performance than training at 105%CP. PMID- 27551940 TI - Exploring Supernumeraries - A New Marker for Screening of B-Chromosomes Presence in the Yellow Necked Mouse Apodemus flavicollis. AB - Since the density of simple sequence repeats (SSRs) may vary between different chromosomes of the same species in eukaryotic genomes, we screened SSRs of the whole genome of the yellow necked mouse, Apodemus flavicollis, in order to reveal SSR profiles specific for animals carrying B chromosomes. We found that the 2200 bp band was amplified by primer (CAG)4AC to a highly increased level in samples with B chromosomes. This quantitative difference (B-marker) between animals with (+B) and without (0B) B chromosomes was used to screen 20 populations (387 animals). The presence/absence of Bs was confirmed in 96.5% of 342 non mosaic individuals, which recommends this method for noninvasive B-presence detection. A group of 45 animals with mosaic and micro B (MUB) karyotypes was considered separately and showed 55.6% of overall congruence between karyotyping and molecular screening results. Relative quantification by qPCR of two different targeted sequences from B-marker indicated that these B-specific fragments are multiplied on B chromosomes. It also confirms our assumption that different types of Bs with variable molecular composition may exist in the same individual and between individuals of this species. Our results substantiate the origin of Bs from the standard chromosomal complement. The B-marker showed 98% sequence identity with the serine/threonine protein kinase VRK1 gene, similarly to findings reported for Bs from phylogenetically highly distant mammalian species. Evolutionarily conserved protein-coding genes found in Bs, including this one in A. flavicollis, could suggest a common evolutionary pathway. PMID- 27551941 TI - Construction of a Hierarchical NiCo2S4@PPy Core-Shell Heterostructure Nanotube Array on Ni Foam for a High-Performance Asymmetric Supercapacitor. AB - In this paper, a hierarchical NiCo2S4@polypyrrole core-shell heterostructure nanotube array on Ni foam (NiCo2S4@PPy/NF) was successfully developed as a bind free electrode for supercapacitors. NiCo2S4@PPy-50/NF obtained under 50 s PPy electrodeposition shows a low charge-transfer resistance (0.31 Omega) and a high area specific capacitance of 9.781 F/cm(2) at a current density of 5 mA/cm(2), which is two times higher than that of pristine NiCo2S4/NF (4.255 F/cm(2)). Furthermore, an asymmetric supercapacitor was assembled using NiCo2S4@PPy-50/NF as positive electrode and activated carbon (AC) as negative electrode. The resulting NiCo2S4@PPy-50/NF//AC device exhibits a high energy density of 34.62 Wh/kg at a power density of 120.19 W/kg with good cycling performance (80.64% of the initial capacitance retention at 50 mA/cm(2) over 2500 cycles). The superior electrochemical performance can be attributed to the combined contribution of both component and unique core-shell heterostructure. The results demonstrate that the NiCo2S4@PPy-50 core-shell heterostructure nanotube array is promising as electrode material for supercapacitors in energy storage. PMID- 27551943 TI - Substrate-Controlled Asymmetric Total Synthesis and Structure Revision of (-) Bisezakyne A. AB - The first asymmetric total synthesis and subsequent structure revision of (-) bisezakyne A, a Laurencia C15 acetogenin from Alpysia oculifera, has been accomplished. Our substrate-controlled synthesis of this oxolane natural product features a highly stereoselective "protecting-group-dependent" intramolecular amide enolate alkylation strategy for the synthesis of the key 9,10-trans-9,12 cis-10-hydroxytetrahydrofuran intermediate through "nonchelate" control. In addition, our synthesis determined the absolute configuration of the halogenated marine natural product. PMID- 27551942 TI - Implementation of the ECHO(r) telementoring model for the treatment of patients with hepatitis C. AB - We aimed to implement the Extension for Community Healthcare Outcomes (ECHO) telementoring model for hepatitis C and to evaluate its outcomes in the health providers. Following the ECHO model, an hepatitis C teleECHO clinic was established at the Hospital Italiano in Argentina. The teleECHO clinic provides support and training to physicians from Patagonia who treat patients with hepatitis C. In order to evaluate the teleECHO clinic outcomes, physicians completed a survey focused on skills and competence in hepatitis C before and after 6 months of participating in the project. The survey consisted of 10 questions, which participants rated from 1 to 7 (1 no ability; 7 highest ability). To analyze the difference before and after participation in the project, Wilcoxon signed-rank test was used. During the first 6 months of implementation of the model, a total of 14 physicians from 12 sites in Patagonia agreed to participate in the survey. The median age of the participants was 42 years. Participants' primary specialties were Hepatology (55%), Infectious Diseases (25%), General Practice (10%), and other (10%). A significant improvement was observed in all the evaluated fields after 6 month of the participation in the teleECHO clinic, namely fibrosis staging, determining appropriate candidates for treatment, and selecting appropriate HCV treatment. In addition, their general interest in hepatitis C increased. We successfully replicated and implemented the first teleECHO clinic in Argentina. Physicians improved their ability to provide best practice care for patients with Hepatitis C. J. Med. Virol. 89:660-664, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27551944 TI - Renal function and novel urinary biomarkers in infants with neonatal encephalopathy. AB - AIM: Perinatal asphyxia is associated with multi-organ injury including acute kidney injury (AKI). New urinary biomarkers may detect more subtle renal injury. METHODS: Urinary biomarkers (albumin, beta-2 microglobulin, cystatin-C, epidermal growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin) were serially measured from days 1 to 7 in term infants with perinatal asphyxia and controls and compared to 'Kidney Disease Improving Global Outcome' scoring of renal injury and to encephalopathy grade. RESULTS: A total of 255 urine samples were taken from infants exposed to perinatal asphyxia (n = 82) and term controls (n = 10). Thirty-nine infants underwent therapeutic hypothermia, four died and 30 infants had acute kidney injury. Infants with acute kidney injury had significantly higher levels of urinary albumin (day 2), cystatin-C (days 1, 2, 3 and 7), neutrophil gelatinase-associated lipocalin (days 2, 3 and 7) and osteopontin (days 2, 3 and 7) and lower epidermal growth factor and uromodulin (day 1) compared to those without AKI. Day 2 cystatin-C predicted AKI with an area under receiver operating characteristic curve of 0.89, p < 0.001, cut-off 9.8 * 104 pg/mL. NE grade II/III infants had significantly elevated levels of urinary cystatin-C, neutrophil gelatinase-associated lipocalin and decreased EGF compared to grade 0/I infants. CONCLUSION: Asphyxiated infants who develop acute kidney injury have significantly altered urinary biomarkers postnatally. Validation of neonatal AKI urinary biomarkers in a large prospective study is required. Long-term follow-up of infants post-asphyxial insult for chronic renal injury is advised. PMID- 27551945 TI - Therapeutic drug monitoring as a measure of proactive pharmacovigilance in child and adolescent psychiatry. AB - INTRODUCTION: Off-label or unlicensed use of psychotropic drugs is common rather than the exception in child and adolescent psychiatry. This use exposes patients to an unknown additional risk of ineffective or even harmful treatment. In addition, treatment with psychotropic drugs during a period of life when the patient undergoes marked developmental hormonal and neurobiological changes often requires different dosing regimes in later life and may result in adverse drug reactions, which are either not seen in adults at all or not in the same frequency. Areas covered: Given these critical safety issues, efficient pharmacovigilance methods as part of routine practice are essential for the improvement of patient care. The purpose of this article is to introduce methods to increase the safety of psychotropic drug use in youngsters. In particular, therapeutic drug monitoring (TDM) as a routine measure of proactive pharmacovigilance is discussed. Expert opinion: Given the special features of psychopharmacological therapy in children and adolescents in day-to-day clinical practise, proactive surveillance by using a close standardized 'patient monitoring' and long-term follow-up with TDM is very important. This approach could minimize the risk of exposing paediatric patients to ineffective treatments of uncertain or unknown risks. PMID- 27551946 TI - The endodermis as a checkpoint for nutrients. AB - Contents 1604 I. 1604 II. 1604 III. 1605 IV. 1608 V. 1609 1609 References 1609 SUMMARY: Plant roots forage the soil for nutrients and transport them upwards to the aerial parts. Nutrients entering the plant are transported through the concentric layers of epidermis, cortex and endodermis before reaching the central vasculature. The endodermis is the innermost cortical cell layer that surrounds the vasculature. The endodermis forms barriers, the Casparian strips and suberin lamellae, which have been assumed to play a major role in controlling nutrient acquisition. However, the molecular network controlling its differentiation has started to be investigated only recently, giving an unprecedented opportunity to address the role of these barriers in plant nutrition. This insight aims to present recent advances regarding endodermis differentiation, its function as a barrier for nutrients and its developmental plasticity, all pointing to a pivotal role of the endodermis as a checkpoint for nutrients. PMID- 27551947 TI - Validity and Reliability of a New Measure of Nursing Experience With Unintended Consequences of Electronic Health Records. AB - Unintended consequences of electronic health records represent undesired effects on individuals or systems, which may contradict initial goals and impact patient care. The purpose of this study was to determine the extent to which a new quantitative measure called the Carrington-Gephart Unintended Consequences of Electronic Health Record Questionnaire (CG-UCE-Q) was valid and reliable. Then, it was used to describe acute care nurses' experience with unintended consequences of electronic health records and relate them to the professional practice environment. Acceptable content validity was achieved for two rounds of surveys with nursing informatics experts (n = 5). Then, acute care nurses (n = 144) were recruited locally and nationally to complete the survey and describe the frequency with which they encounter unintended consequences in daily work. Principal component analysis with oblique rotation was applied to evaluate construct validity. Correlational analysis with measures of the professional practice environment and workarounds was used to evaluate convergent validity. Test-retest reliability was measured in the local sample (N = 68). Explanation for 63% of the variance across six subscales (patient safety, system design, workload issues, workarounds, technology barriers, and sociotechnical impact) supported construct validity. Relationships were significant between subscales for electronic health record-related threats to patient safety and low autonomy/leadership (P < .01), poor communication about patients (P < .01), and low control over practice (P < .01). The most frequent sources of unintended consequences were increased workload, interruptions that shifted tasks from the computer, altered workflow, and the need to duplicate data entry. Convergent validity of the CG-UCE-Q was moderately supported with both the context and processes of workarounds with strong relationships identified for when nurses perceived a block and altered process to work around it to subscales in the CG UCE-Q for electronic health record system design (P < .01) and technological barriers (P < .01). PMID- 27551948 TI - Effect of Zinc Incorporation on the Performance of Red Light Emitting InP Core Nanocrystals. AB - This report presents a systematic study on the effect of zinc (Zn) carboxylate precursor on the structural and optical properties of red light emitting InP nanocrystals (NCs). NC cores were assessed using X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), energy-dispersive X-ray spectroscopy (EDX), and high-resolution transmission electron microscopy (HRTEM). When moderate Zn:In ratios in the reaction pot were used, the incorporation of Zn in InP was insufficient to change the crystal structure or band gap of the NCs, but photoluminescence quantum yield (PLQY) increased dramatically compared with pure InP NCs. Zn was found to incorporate mostly in the phosphate layer on the NCs. PL, PLQY, and time-resolved PL (TRPL) show that Zn carboxylates added to the precursors during NC cores facilitate the synthesis of high-quality InP NCs by suppressing nonradiative and sub-band-gap recombination, and the effect is visible also after a ZnS shell is grown on the cores. PMID- 27551949 TI - Quantification of Compactness and Local Order in the Ensemble of the Intrinsically Disordered Protein FCP1. AB - Intrinsically disordered protein regions (IDRs) partially or completely lack a cooperatively folded structure under native conditions, preventing their equilibrium state from being adequately described by a single structural model. As a direct consequence of their disorder, remarkably few experimental studies have quantified the ensembles IDRs adopt in solution. Here, we conduct unbiased computer simulations of the RAP74 interaction motif from the human phosphatase FCP1 in the unbound state, which provides an ensemble in quantitative agreement with both experimental NMR chemical shift information and small-angle X-ray scattering data. The partially alpha-helical short linear motif found in the C terminus of FCP1 has been the subject of extensive biophysical characterization aimed at developing a molecular description for the mechanism of coupled folding and binding and establishing the functional relevance of partial order in the unbound state. The analysis presented here yields a remarkably consistent molecular picture enumerating the diversity of structures present in a "partially formed" helix. Specific interactions, including anticorrelations in backbone dihedral angle fluctuations as well as the transient formation of a helix stabilizing salt bridge, stabilize the preformed structure in the unbound state. The general consequences of these findings for mechanistic analysis of protein protein interactions are discussed. PMID- 27551950 TI - Bronchiectasis in yellow nail syndrome. AB - BACKGROUND AND OBJECTIVE: Yellow nail syndrome (YNS) is a rare and poorly described disease process. In this case-control study, clinical features and findings on HRCT were compared with idiopathic bronchiectasis (IBx). METHODS: A review of all patients attending an adult bronchiectasis clinic between 2007 and 2013 identified 25 YNS patients. IBx patients were matched in a 2:1 ratio for age, duration of symptoms and gender. RESULTS: Median age of onset was 53 years. There were 12 male and 23 Caucasian YNS patients. Respiratory manifestations included chronic productive cough (100%), chronic rhinosinusitis (88%), pleural effusions (20%) and lymphoedema (12%). Chest symptoms preceded yellow nails in the majority (68%). Abnormal nails persisted at follow-up in 23 of 25 patients but improved in 14. In both disorders, there was symmetrical, predominantly lower lobe bronchiectasis on HRCT. Extent (P = 0.04), severity (P = 0.03) and bronchial wall thickness (P = 0.05) scores were lower in YNS, with less upper and middle lobe disease. Multivariate analysis showed an independent association with increased mucus plugging in YNS. There was a similar prevalence of Pseudomonas aeruginosa infection and mild lung function abnormalities. CONCLUSION: Bronchiectasis in YNS is less severe than IBx but is associated with increased mucus plugging, onset is in middle age and there is no female predominance. Treatment targeted at improved secretion clearance may improve both chest and nail symptoms, with consideration of long-term macrolide antibiotics. PMID- 27551951 TI - Competing Interfacial Reconstruction Mechanisms in La0.7Sr0.3MnO3/SrTiO3 Heterostructures. AB - Interface coupling between complex oxides offers unique possibilities to tailor materials properties and stabilize novel ground states. Understanding the structural reconstruction of the corner-shared octahedral framework and the charge redistribution are crucial for controlling interfacial properties in oxide electronics. Here, we study the interfacial oxygen octahedral behavior in La0.7Sr0.3MnO3/SrTiO3 heterostructure, by directly imaging the oxygen octahedra at the atomic scale and extracting the structural parameters. We combine these experimental results with electronic structure calculations to elucidate the effect of reconstructed MnO6 octahedral geometry on increased interfacial magnetization and conductivity. The Mn valence profiles near the interface are quantitatively analyzed and compared at variant temperatures, revealing the insulating nature of interfacial manganite with reduced Mn valence. This study suggests a pathway to manipulate the interfacial properties and creation of new ground states in complex oxide heterostructures by tuning competing structural and electronic parameters. PMID- 27551953 TI - Essential Role of the Linker Region in the Higher Catalytic Efficiency of a Bifunctional MsrA-MsrB Fusion Protein. AB - Many bacteria, particularly pathogens, possess methionine sulfoxide reductase A (MsrA) and B (MsrB) as a fusion form (MsrAB). However, it is not clear why they possess a fusion MsrAB form rather than the separate enzymes that exist in most organisms. In this study, we performed biochemical and kinetic analyses of MsrAB from Treponema denticola (TdMsrAB), single-domain forms (TdMsrA and TdMsrB), and catalytic Cys mutants (TdMsrAB(C11S) and TdMsrAB(C285S)). We found that the catalytic efficiency of both MsrA and MsrB increased after fusion of the domains and that the linker region (iloop) that connects TdMsrA and TdMsrB is required for the higher catalytic efficiency of TdMsrAB. We also determined the crystal structure of TdMsrAB at 2.3 A, showing that the iloop mainly interacts with TdMsrB via hydrogen bonds. Further kinetic analysis using the iloop mutants revealed that the iloop-TdMsrB interactions are critical to MsrB and MsrA activities. We also report the structure in which an oxidized form of dithiothreitol, an in vitro reductant for MsrA and MsrB, is present in the active site of TdMsrA. Collectively, the results of this study reveal an essential role of the iloop in maintaining the higher catalytic efficiency of the MsrAB fusion enzyme and provide a better understanding of why the MsrAB enzyme exists as a fused form. PMID- 27551952 TI - Activation of the Constitutive Androstane Receptor by Monophthalates. AB - Humans in industrialized areas are continuously exposed to phthalate plasticizers, prompting concerns of their potential toxicities. Previous studies from our laboratory and others have shown that various phthalates activate several mammalian nuclear receptors, in particular the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), and the peroxisomal proliferator activated receptors (PPARs), although often at concentration levels of questionable relevance to human exposure. We discovered that di(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DiNP), two of the highest volume production agents, were potent activators of human CAR2 (hCAR2), a unique human CAR splice variant and, to a lesser degree, human PXR (hPXR). These diphthalates undergo rapid metabolism in mammalian systems, initially to their major monophthalate derivatives MEHP and MiNP. Although MEHP and MiNP are reported activators of the rodent PPARs, with lower affinities for the corresponding human PPARs, it remains unclear whether these monophthalate metabolites activate hCAR2 or hPXR. In this investigation, we assessed the relative activation potential of selected monophthalates and other low molecular weight phthalates against hCAR, the most prominent hCAR splice variants, as well as hPXR and human PPAR. Using transactivation and mammalian two-hybrid protein interaction assays, we demonstrate that these substances indeed activate hCARs and hPXR but to varying degrees. MEHP and MiNP exhibit potent activation of hCAR2 and hPXR with higher affinities for these receptors than for the hPPARs. The rank order potency for MEHP and MiNP was hCAR2 > hPXR > hPPARs. Results from primary hepatocyte experiments also reflect the MEHP and MiNP upregulation of the respective human target genes. We conclude that both di- and monophthalates are potently selective hCAR2 activators and effective hPXR activators. These results implicate these targets as important mediators of selective phthalate effects in humans. The striking differential affinities for these compounds between human and rodent nuclear receptors further implies that biological results obtained from rodent models may be of only limited relevance for interpolating phthalate-mediated effects in humans. PMID- 27551954 TI - Evaluation of a novel device, high-intensity focused ultrasound with a contact cooling for subcutaneous fat reduction. AB - BACKGROUND: Non-invasive devices for fat reduction involving high-intensity focused ultrasound (HIFU) are attracting attention. HIFU can deliver energy to the desired depth and can ablate subcutaneous adipose tissue (SAT), but purpura and pain may still limit its use. OBJECTIVES: The aim of this study was to investigate the effects of a novel HIFU device for fat destruction with a contact cooling system compared to HIFU without contact cooling. METHODS: A group of three pigs were administered a series of four HIFU treatments with or without contact cooling over a period of 12 weeks. Energy fluence parameters ranged from 60 to 300 J/cm2 . Immediately after the treatment and at 1, 4, and 12 weeks, the tissue was studied by hematoxylin and eosin (H&E), Masson-trichrome, toluidine blue, CD68 staining, and transmission electron microscopy. Three human volunteers also received treatment with this HIFU device with cooling and were evaluated subjectively and objectively by computed tomography (CT). RESULTS: HIFU treatment with a contact cooling decreased the skin surface temperature and prevented epidermal damage. Ecchymosis was observed on the non-cooled area immediately after HIFU treatment, but not on the cooled area. Histological analyses on both areas (cooled and non-cooled) revealed disrupted adipocytes in the treatment area immediately, at 1 and 4 weeks following treatment. Lipophagic histiocytic fat necrosis was evident at 4 weeks. Finally, at 12 weeks all inflammation subsided, and the lobules were markedly atrophied with reduced SAT thickness. The human volunteers experienced reduction of a few centimeter-range reduction in waist circumference after 4 weeks and pain was tolerable without bruising. CONCLUSIONS: HIFU treatment with a cooling system efficiently destroyed adipocytes. This novel HIFU device with an added contact cooling system may provide an effective, safe and less painful treatment as a non-invasive device for fat reduction. Lasers Surg. Med. 48:878-886, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27551955 TI - Factors Associated with Age Affect Willingness to Engage in Early End-of-Life Communication Using Electronic Health Record-Tethered Patient Portals. PMID- 27551956 TI - Topical Beta-Blockers and Cardiovascular Mortality: Systematic Review and Meta Analysis with Data from the EPIC-Norfolk Cohort Study. AB - PURPOSE: To determine if topical beta-blocker use is associated with increased cardiovascular mortality, particularly among people with self-reported glaucoma. METHODS: All participants who participated in the first health check (N = 25,639) of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort (1993 2013) were included in this prospective cohort study, with a median follow-up of 17.0 years. We determined use of topical beta-blockers at baseline through a self reported questionnaire and prescription check at the first clinical visit. Cardiovascular mortality was ascertained through data linkage with the Office for National Statistics mortality database. Hazard ratios (HRs) were estimated using multivariable Cox regression models. Meta-analysis of the present study's results together with other identified literature was performed using a random effects model. RESULTS: We did not find an association between the use of topical beta blockers and cardiovascular mortality (HR 0.93, 95% confidence interval, CI, 0.67 1.30). In the 514 participants with self-reported glaucoma, no association was found between the use of topical beta-blockers and cardiovascular mortality (HR 0.89, 95% CI 0.56-1.40). In the primary meta-analysis of four publications, there was no evidence of an association between the use of topical beta-blockers and cardiovascular mortality (pooled HR estimate 1.10, 95% CI 0.84-1.36). CONCLUSION: Topical beta-blockers do not appear to be associated with excess cardiovascular mortality. This evidence does not indicate that a change in current practice is warranted, although clinicians should continue to assess individual patients and their cardiovascular risk prior to commencing topical beta-blockers. PMID- 27551957 TI - Proteome Analyses Using iTRAQ Labeling Reveal Critical Mechanisms in Alternate Bearing Malus prunifolia. AB - Alternate bearing (AB) trees, including Malus prunifolia, are characterized by alternating cycles of heavy (ON tree) and low (OFF tree) fruit loads. The mechanisms regulating the AB phenomenon have not been fully characterized. We completed an iTRAQ-based investigation of M. prunifolia to identify the proteome and metabolic differences between the leaves of ON and OFF trees. We identified 667 differentially expressed proteins, and they influenced multiple biochemical pathways, including photosynthesis, carbohydrate metabolism, glycolysis, protein processing, redox activities, and secondary metabolism. Bioinformatics analyses indicated photosynthesis was the most significant biological process affecting the AB. We observed that 47 photosynthetic proteins affecting photosystem I and II reaction centers, cytochrome b6/f complex, electron transport, and light harvesting chlorophyll were less abundant in ON tree leaves than in OFF tree leaves. Additionally, physiological analyses validated the potential metabolic activities. Nitrogen and phosphorus contents were significantly higher in ON tree leaves, while potassium levels were lower. Starch content, ZR, GA4+7 levels, and flower control gene expression levels (i.e., MdFT1, MdLFY, MdAP1, and MdSPL9) were lower in ON tree leaves than in OFF tree leaves, suggesting they affected the AB phenotype. Our findings help further investigate on the photosynthesis as well as other processes in AB. Those identified DEPs and important biological processes can be useful theoretical basis and provide new insights into the molecular mechanisms regulating AB in perennial woody plants. PMID- 27551958 TI - Synthesis of an Isomer of the Decalinoyltetramic Acid Methiosetin by a Stereocontrolled IMDA Reaction of a Metal-Chelated 3-Trienoyltetramate. AB - An isomer of the 3-decalinoyltetramic acid methiosetin was synthesized for the first time. The decalin moiety was established by a late-stage intramolecular Diels-Alder cyclization catalyzed by Me2AlCl or La(OTf)3. Its high diastereoselectivity arose from stereoinduction by a well-defined metal O,O chelate complex of the 3-acyltetramic acid moiety. The nature of the metal and the bulkiness of the residues at the tetramic acid chelator are decisive for the stereochemical outcome. PMID- 27551959 TI - The Association Between HIV Disclosure Status and Perceived Barriers to Care Faced by Women Living with HIV in Latin America, China, Central/Eastern Europe, and Western Europe/Canada. AB - Generally, women are less likely than men to disclose their HIV status. This analysis examined the relationship between HIV disclosure and (1) perceived barriers to care and (2) quality of life (QoL) for women with HIV. The ELLA (EpidemioLogical study to investigate the popuLation and disease characteristics, barriers to care, and quAlity of life for women living with HIV) study enrolled HIV-positive women aged >=18 years. Women completed the 12-item Barriers to Care Scale (BACS) questionnaire. QoL was assessed using the Health Status Assessment. BACS and QoL were stratified by dichotomized HIV disclosure status (to anyone outside the healthcare system). Multilevel logistic regression analysis was used to identify factors associated with disclosure. Of 1945 patients enrolled from Latin America, China, Central/Eastern Europe, and Western Europe/Canada between July 2012 and September 2013, 1929 were included in the analysis (disclosed, n = 1724; nondisclosed, n = 205). Overall, 55% of patients lived with a husband/partner, 53% were employed, and 88% were receiving antiretroviral therapy. Patients who were with a serodiscordant partner were more likely to disclose (p = 0.0003). China had a disproportionately higher percentage of participants who did not disclose at all (nearly 30% vs. <15% for other regions). Mean BACS severity scores for medical/psychological service barriers and most personal resource barriers were significantly lower for the disclosed group compared with the nondisclosed group (p <= 0.02 for all). Compared with the disclosed group, the nondisclosed group reported statistically significantly higher (p <= 0.03) BACS item severity scores for 8 of the 12 potential barriers to care. The disclosed group reported better QoL. Overall, HIV nondisclosure was associated with more severe barriers to accessing healthcare by women with HIV. PMID- 27551960 TI - The ACP Guidelines for Treatment of Chronic Insomnia: The Challenge of Implementation. PMID- 27551962 TI - Progress and Challenges in Scaling Up Laboratory Monitoring of HIV Treatment. AB - In a perspective on Habiyambere and colleagues, Peter Kilmarx and Raiva Simbi discuss the disconnect between HIV testing instrument capacity and utilization. PMID- 27551963 TI - Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis. AB - BACKGROUND: As for the association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to pediatric asthma, results of published studies yielded conflicts. A systematic review was conducted on the relationship between childhood asthma and VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236). METHODS: PubMed, Web of Science, CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) database were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated. RESULTS: Overall results suggested that there was a statistically significant association between ApaI polymorphism and childhood asthma in homozygote model (OR = 1.674, 95%CI = 1.269-2.208, P < 0.001) and allele model (OR = 1.221, 95%CI = 1.084-1.375, P = 0.001). Stratification by ethnicity revealed a statistical association in Asians (OR = 1.389, 95%CI = 1.178-1.638, P < 0.001). There was some evidence of an association between BsmI polymorphism and childhood asthma in the homozygote (OR = 1.462, 95%CI = 1.016-2.105, P = 0.041) and allele models (OR = 1.181, 95%CI = 1.006-1.386, P = 0.042). This association reached significance only in the Caucasian group (OR = 1.236, 95%CI = 1.029 1.485, P = 0.023). For FokI, a statistical association was detected in dominant model (OR = 1.281, 95%CI = 1.055-1.555, P = 0.012); this association was significant in allele model (OR = 1.591, 95%CI = 1.052-2.405, P = 0.028) in Caucasian. CONCLUSION: ApaI polymorphism plays a particular role in childhood asthma in Asians. FokI polymorphism may be connected with pediatric asthma in Caucasian population. And BsmI polymorphism marginally contributes to childhood asthma susceptibility, while there might be no association between TaqI polymorphism and childhood asthma risk. Pediatr Pulmonol. 2017;52:423-429. (c) 2016 Wiley Periodicals, Inc. PMID- 27551964 TI - The Qualification of Outcome after Cervical Spine Surgery by Patients Compared to the Neck Disability Index. AB - OBJECTIVE: The Neck Disability Index (NDI) is a patient self-assessed outcome measurement tool to assess disability, and that is frequently used to evaluate the effects of the treatment of neck-related problems. In individualized medicine it is mandatory that patients can interpret data in order to choose a treatment. A change of NDI or an absolute NDI is generally meaningless to a patient. Therefore, a correlation between the qualification of the clinical situation rated by the patient and the NDI score was evaluated. METHODS: Patients who completed an NDI after anterior surgery because of symptomatic single level degenerative cervical disc disease were asked one month after completion of the NDI to qualify their clinical situation of a 5-item Likert scale varying from excellent to bad. Since a clear distinction between the categories was not possible based on the total NDI score, a ROC-curve was built, and the AUC computed in order to estimate best dichotomization in qualification of the clinical situation. The best corresponding cut-off point for the NDI total score was found by studying sensitivity and specificity for all possible cut-off points. RESULTS: 102 patients were included. The highest AUC was obtained by dichotomizing the qualification into a group with good outcome and less-good outcome. The highest sensitivity and specificity for the dichotomized qualification as good outcome corresponded to a NDI <= 7. Sensitivity was 81.08% and specificity was 78.57%. CONCLUSION: This is the first study that correlated the qualification of the situation by the patients themselves and NDI. An NDI <= 7 corresponded to a good outcome according to the patients. This is valuable information to inform patients in their decision for any treatment. PMID- 27551965 TI - Factors Affecting the Radiosensitivity of Hexaploid Wheat to gamma-Irradiation: Radiosensitivity of Hexaploid Wheat (Triticum aestivum L.) [Corrected]. AB - Understanding the radiosensitivity of plants, an important factor in crop mutation breeding programs, requires a thorough investigation of the factors that contribute to this trait. In this study, we used the highly radiosensitive wheat (Triticum aestivum L.) variety HY1 and J411, a gamma-irradiation-insensitive control, which were screened from a natural population, to examine the factors affecting radiosensitivity, including free radical content and total antioxidant capacity, as well as the expression of TaKu70 and TaKu80 (DNA repair-related genes) as measured by real-time PCR. We also investigated the alternative splicing of this gene in the wild-type wheat ecotype by sequence analysis. Free radical contents and total antioxidant capacity significantly increased upon exposure of HY1 wheat to gamma-irradiation in a dose-dependent manner. By contrast, in J411, the free radical contents exhibited a similar trend, but the total antioxidant capacity exhibited a downward trend upon increasing gamma irradiation. Additionally, we detected dose-dependent increases in TaKu70 and TaKu80 expression levels in gamma-irradiated HY1, while in J411, TaKu70 expression levels increased, followed by a decline. We also detected alternative splicing of TaKu70 mRNA, namely, intron retention, in HY1 but not in J411. Our findings indicate that gamma-irradiation induces oxidative stress and DNA damage in hexaploid wheat, resulting in growth retardation of seedlings, and they suggest that TaKu70 may play a causal role in radiosensitivity in HY1. Further studies are required to exploit these factors to improve radiosensitivity in other wheat varieties. PMID- 27551967 TI - Isolation of Intact and Functional Melanosomes from the Retinal Pigment Epithelium. AB - Melanosomes of retinal pigment epithelium (RPE) have many vision supporting functions. Melanosome research would benefit from a method to isolate pure and characterized melanosomes. Sucrose gradient centrifugation is the most commonly used method for isolation of RPE melanosomes, but the isolated products are insufficiently characterized and their quality is unclear. Here we introduce a new gentle method for fractionation of porcine RPE that produces intact functional melanosomes with minimal cross-contamination from other cell organelles. The characterization of isolated organelles was conducted with several methods confirming the purity of the isolated melanosomal fraction (transmission electron microscopy, immunoblotting) and presence of the melanosomal membrane (fluorescence staining of melanosomal membrane, zeta potential measurement). We demonstrate that our isolation method produces RPE melanosomes with the ability to generate free phosphate (Pi) from ATP thereby proving that many membrane proteins remain functional after isolation. The isolated porcine RPE melanosomes represented V-type H+ATPase activity that was demonstrated with bafilomycin A1, a specific V-ATPase inhibitor. We anticipate that the isolation method described here can easily be optimized for the isolation of stage IV melanosomes from other pigmented cell types and tissues. PMID- 27551966 TI - Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival. AB - Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285-0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365-1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248-1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies. PMID- 27551968 TI - Differential Releases of Dopamine and Neuropeptide Y from Histamine-Stimulated PC12 Cells Detected by an Aptamer-Modified Nanowire Transistor. AB - Silicon nanowire field-effect transistors modified with specific aptamers can directly detect the minute dopamine and neuropeptide Y released from cells. The binding of these molecules to the aptamers results in a conductance change of the transistor biosensor and illustrates the differential releasing mechanisms of these molecules stored in various vesicle pools. PMID- 27551969 TI - Smartphone-Based Cardiac Rehabilitation Program: Feasibility Study. AB - We introduce a cardiac rehabilitation program (CRP) that utilizes only a smartphone, with no external devices. As an efficient guide for cardiac rehabilitation exercise, we developed an application to automatically indicate the exercise intensity by comparing the estimated heart rate (HR) with the target heart rate zone (THZ). The HR is estimated using video images of a fingertip taken by the smartphone's built-in camera. The introduced CRP app includes pre exercise, exercise with intensity guidance, and post-exercise. In the pre exercise period, information such as THZ, exercise type, exercise stage order, and duration of each stage are set up. In the exercise with intensity guidance, the app estimates HR from the pulse obtained using the smartphone's built-in camera and compares the estimated HR with the THZ. Based on this comparison, the app adjusts the exercise intensity to shift the patient's HR to the THZ during exercise. In the post-exercise period, the app manages the ratio of the estimated HR to the THZ and provides a questionnaire on factors such as chest pain, shortness of breath, and leg pain during exercise, as objective and subjective evaluation indicators. As a key issue, HR estimation upon signal corruption due to motion artifacts is also considered. Through the smartphone-based CRP, we estimated the HR accuracy as mean absolute error and root mean squared error of 6.16 and 4.30bpm, respectively, with signal corruption due to motion artifacts being detected by combining the turning point ratio and kurtosis. PMID- 27551970 TI - Hearing Loss in HIV-Infected Children in Lilongwe, Malawi. AB - INTRODUCTION: With improved access to antiretroviral therapy (ART), HIV infection is becoming a chronic illness. Preliminary data suggest that HIV-infected children have a higher risk of disabilities, including hearing impairment, although data are sparse. This study aimed to estimate the prevalence and types of hearing loss in HIV-infected children in Lilongwe, Malawi. METHODS: This was a cross-sectional survey of 380 HIV-infected children aged 4-14 years attending ART clinic in Lilongwe between December 2013-March 2014. Data was collected through pediatric quality of life and sociodemographic questionnaires, electronic medical record review, and detailed audiologic testing. Hearing loss was defined as >20 decibels hearing level (dBHL) in either ear. Predictors of hearing loss were explored by regression analysis generating age- and sex-adjusted odds ratios. Children with significant hearing loss were fitted with hearing aids. RESULTS: Of 380 patients, 24% had hearing loss: 82% conductive, 14% sensorineural, and 4% mixed. Twenty-one patients (23% of those with hearing loss) were referred for hearing aid fitting. There was a higher prevalence of hearing loss in children with history of frequent ear infections (OR 7.4, 4.2-13.0) and ear drainage (OR 6.4, 3.6-11.6). Hearing loss was linked to history of WHO Stage 3 (OR 2.4, 1.2 4.5) or Stage 4 (OR 6.4, 2.7-15.2) and history of malnutrition (OR 2.1, 1.3-3.5), but not to duration of ART or CD4. Only 40% of caregivers accurately perceived their child's hearing loss. Children with hearing impairment were less likely to attend school and had poorer emotional (p = 0.02) and school functioning (p = 0.04). CONCLUSIONS: There is an urgent need for improved screening tools, identification and treatment of hearing problems in HIV-infected children, as hearing loss was common in this group and affected school functioning and quality of life. Clear strategies were identified for prevention and treatment, since most hearing loss was conductive in nature, likely due to frequent ear infections, and many children with hearing loss qualified for hearing aids. Screening strategies need to be developed and tested since caregivers were not reliable at identifying hearing loss, and often mis-identified children with normal hearing as having hearing loss. Children with frequent ear infections, ear drainage, TB, severe HIV disease, or low BMI should receive more frequent ear assessments and hearing evaluations. PMID- 27551972 TI - Examining courtesy stigma among foreign health care workers caring for persons with Alzheimer's disease: A focus group study. AB - Studies have shown that courtesy stigma is common among informal caregivers of persons with Alzheimer's disease. Guided by attribution theory and using focus group methodology, we examined this topic among 12 foreign health care workers. Findings revealed that stigma is noticeable in the everyday reality of foreign workers caring for persons with dementia and that its management is shaped by beliefs and knowledge about the disease in their original countries, and by knowledge gained as caregivers. Greater understanding of stigma among foreign workers is crucial for advancing knowledge in the area and for improving the care provided to persons with Alzheimer's disease. PMID- 27551973 TI - Genome-Wide Identification, Expression Diversication of Dehydrin Gene Family and Characterization of CaDHN3 in Pepper (Capsicum annuum L.). AB - Dehydrins (DHNs) play a crucial role in enhancing abiotic stress tolerance in plants. Although DHNs have been identified and characterized in many plants, there is little known about Capsicum annuum L., one of the economically important vegetable crops. In this study, seven CaDHNs in the pepper genome were identified, which could be divided into two classes: YnSKn- and SKn-type, based on their highly conserved domains. Quantitative real-time PCR (qRT-PCR) results showed that the seven DHN genes were expressed in all tissues and might be involved in the growth and development of pepper. The gene expression profiles analysis suggested that most of the CaDHN genes were induced by various stresses (low temperature, salt and mannitol) and signaling molecules (ABA, SA and MeJA). Furthermore, the CaDHN3 (YSK2)-silenced pepper plants showed obvious lower resistance to abiotic stresses (cold, salt and mannitol) than the control plants (TRV2:00). So the CaDHN3 might act as a positive role in resisting abiotic stresses. This study lays the foundation for further studies into the regulation of their expression under various conditions. PMID- 27551971 TI - The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children. AB - Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes. PMID- 27551975 TI - Effects of Wolbachia on mitochondrial DNA variation in populations of Athetis lepigone (Lepidoptera: Noctuidae) in China. AB - Wolbachia are endosymbiotic bacteria that infect arthropods and incompatibility among strains can affect gene flow within host insect populations that can significantly result in host mitochondrial DNA (MtDNA) variation within or among populations. The effects of Wolbachia infection on Athetis lepigone MtDNA variation were studied across 12 geographical populations sampled from North China. Mitochondrial COI gene and Wolbachia wsp gene were both obtained from 423 individuals, including 46 Wolbachia infected and 377 uninfected individuals. Average A. lepigone infection rate was 11% (range: 0 to 26%), and wsp sequence variation defined three distinct Wolbachia strains; wLep1, wLep2, and wLep3, respectively. A haplotype network showed no relationship between A. lepigone MtDNA haplotype and Wolbachia infection. Furthermore, haplotype variation mainly exists within populations, although the proportion of variation is higher within uninfected compared to infected individuals. The lack of correlation between A. lepigone haplotype and Wolbachia strain, suggests symbiont infection may not affect mating compatibility or gene flow within host populations in China. PMID- 27551976 TI - A view from the virology research laboratory. PMID- 27551974 TI - Antileukemia Effect of Ciclopirox Olamine Is Mediated by Downregulation of Intracellular Ferritin and Inhibition beta-Catenin-c-Myc Signaling Pathway in Glucocorticoid Resistant T-ALL Cell Lines. AB - Ciclopirox olamine (CPX) is an antifungal drug that has been reported to have antitumor effects. In this study we investigated the antileukemia effects and the possible mechanisms of CPX on glucocorticoid (GC)-resistant T-cell acute lymphoblastic leukemia (T-ALL) cell lines. The results indicated that CPX inhibited the growth of GC-resistant T-ALL cells in a time- and dose-dependent manner, and this effect was closely correlated with the downregulation of intracellular ferritin. CPX induced cell cycle arrest at G1 phase by upregulation of cyclin-dependent kinase (CDK) inhibitor of p21 and downregulation of the expressions of cyclin D, retinoblastoma protein (Rb), and phosphorylated Rb (pRb). CPX also enhanced apoptotic cell death by downregulation of anti-apoptotic proteins such as Bcl-2, Bcl-xL, and Mcl-1. More importantly, CPX demonstrated a strong synergistic antileukemia effect with GC and this effect was mediated, at least in part, by inhibition of the beta-catenin-c-Myc signaling pathway. These findings suggest that CPX could be a promising antileukemia drug, and modulation of the intracellular ferritin expression might be an effective method in the treatment of ALL. Therefore, integrating CPX into the current GC-containing ALL protocols could lead to the improvement of the outcome of ALL, especially GC resistant ALL. PMID- 27551977 TI - Dynamic Balanced Reach: A Temporal and Spectral Analysis Across Increasing Performance Demands. AB - Standing balanced reach is a fundamental task involved in many activities of daily living that has not been well analyzed quantitatively to assess and characterize the multisegmental nature of the body's movements. We developed a dynamic balanced reach test (BRT) to analyze performance in this activity; in which a standing subject is required to maintain balance while reaching and pointing to a target disk moving across a large projection screen according to a sum-of-sines function. This tracking and balance task is made progressively more difficult by increasing the disk's overall excursion amplitude. Using kinematic and ground reaction force data from 32 young healthy subjects, we investigated how the motions of the tracking finger and whole-body center of mass (CoM) varied in response to the motion of the disk across five overall disk excursion amplitudes. Group representative performance statistics for the cohort revealed a monotonically increasing root mean squared (RMS) tracking error (RMSE) and RMS deviation (RMSD) between whole-body CoM (projected onto the ground plane) and the center of the base of support (BoS) with increasing amplitude (p < 0.03). Tracking and CoM response delays remained constant, however, at 0.5 s and 1.0 s, respectively. We also performed detailed spectral analyses of group representative response data for each of the five overall excursion amplitudes. We derived empirical and analytical transfer functions between the motion of the disk and that of the tracking finger and CoM, computed tracking and CoM responses to a step input, and RMSE and RMSD as functions of disk frequency. We found that for frequencies less than 1.0 Hz, RMSE generally decreased, while RMSE normalized to disk motion amplitude generally increased. RMSD, on the other hand, decreased monotonically. These findings quantitatively characterize the amplitude- and frequency-dependent nature of young healthy tracking and balance in this task. The BRT is not subject to floor or ceiling effects, overcoming an important deficiency associated with most research and clinical instruments used to assess balance. This makes a comprehensive quantification of young healthy balance performance possible. The results of such analyses could be used in work space design and in fall-prevention instructional materials, for both the home and work place. Young healthy performance represents "exemplar" performance and can also be used as a reference against which to compare the performance of aging and other clinical populations at risk for falling. PMID- 27551978 TI - The Current State of Critical Limb Ischemia: A Systematic Review. AB - Importance: Chronic critical limb ischemia, marked by intractable lower extremity ischemic rest pain and tissue loss, is a highly morbid condition that leads to the loss of ambulation and decreased quality of life. It is associated with a high risk of limb loss and mortality and presents a significant economic burden to society. Objective: To review the current state of epidemiology, pathophysiology, diagnosis, and treatment of critical limb ischemia. Evidence Review: An extensive literature search of the subject matter was conducted on material published in English between 1980 and 2016; both landmark and recently published articles were evaluated. Articles were reviewed if they included the terms critical limb ischemia, ischemic rest pain, gangrene, or extremity ulcers. Findings: Critical limb ischemia represents the end stage of peripheral arterial disease. Because peripheral arterial disease is most commonly caused by atherosclerosis, critical limb ischemia is heavily associated with smoking and diabetes. Revascularization is the cornerstone of therapy to prevent limb amputation, and both open vascular surgery and endovascular therapy play a key role in the treatment of patients with critical limb ischemia. However, few scientific data are available to identify the optimal revascularization strategy, which has led to a significant amount of variability and equipoise in the treatment of this condition. Medical therapy plays a significant role in optimizing coexistent cardiovascular risk factors and a limited role in improving limb outcomes in nonrevascularizable disease. Conclusions and Relevance: Understanding critical limb ischemia and its treatment strategies is important for providing the best care for affected patients. Currently, ongoing randomized clinical trials in North America and the United Kingdom aim to provide data to support the best management of these patients. PMID- 27551979 TI - Mucosal Healing of Pediatric Simple Ulcer Treated With Infliximab and Methotrexate. PMID- 27551980 TI - Large vessel vasculitis: the search for response biomarkers. PMID- 27551981 TI - Characterization of a sub-assembly of 3D position sensitive cadmium zinc telluride detectors and electronics from a sub-millimeter resolution PET system. AB - Cadmium zinc telluride (CZT) offers key advantages for small animal positron emission tomography (PET), including high spatial and energy resolution and simple metal deposition for fabrication of very small pixel arrays. Previous studies have investigated the intrinsic spatial, energy, and timing resolution of an individual sub-millimeter resolution CZT detector. In this work we present the first characterization results of a system of these detectors. The 3D position sensitive dual-CZT detector module and readout electronics developed in our lab was scaled up to complete a significant portion of the final PET system. This sub system was configured as two opposing detection panels containing a total of twelve [Formula: see text] mm monolithic CZT crystals for proof of concept. System-level characterization studies, including optimizing the trigger threshold of each channel's comparators, were performed. 68Ge and 137Cs radioactive isotopes were used to characterize the energy resolution of all 468 anode channels in the sub-system. The mean measured global 511 keV photopeak energy resolution over all anodes was found to be [Formula: see text]% FWHM after correction for photon interaction depth-dependent signal variation. The measured global time resolution was 37 ns FWHM, a parameter to be further optimized, and the intrinsic spatial resolution was 0.76 mm FWHM. PMID- 27551982 TI - Quintuplets: 5 Cases of NEC. Are There Other Risk Factors? AB - OBJECTIVE: To review a case of quintuplets with all babies developing necrotizing enterocolitis. METHODS: A retrospective study of preterm quintuplets all developing necrotizing enterocolitis. Clinical outcomes were reviewed. RESULTS: Quintuplets were born at 24 weeks gestation. Each baby developed NEC and was treated. One baby died. Currently the remaining 4 infants are on full enteral nutrition. CONCLUSION: Further studies are needed to better understand this emerging population of multiple birth pregnancy and the frequency of NEC development. PMID- 27551983 TI - Viral-associated malignancies in Africa: are viruses 'infectious traces' or 'dominant drivers'? AB - Since the discovery of Epstein-Barr virus (EBV) the first human virus associated with cancer in 1964, the number of human malignancies associated with viruses has grown. A review of cancer incidence reveals substantial variation in the incidence of such cancers around the world. In some parts of Africa, the majority of cancers are caused by infectious agents. However, there remain huge challenges in measuring the burden of cancer, especially in sub-Saharan Africa. Despite this limitation, it is clear that viral-associated malignancies are key drivers of cancer incidence rates in Africa. Prevention is available through vaccination for some but development of vaccines for others remains an important the goal. PMID- 27551984 TI - IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation. AB - Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORgammat and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD. PMID- 27551985 TI - The immunomodulatory effects of a commercial antiviral homeopathic compound in C57BL/6 mice, pre and post vaccine challenge. AB - Homeopathic remedies have been selectively employed in human medicine since Hahneman introduced the concept in 1828. While the use of homeopathy is regionally popular in both human and veterinary medicine, there is still a significant lack of scientific evidence supporting its efficacy. This is likely due to an absence of studies evaluating the mechanism of action of these compounds. Engystol(r) an FDA-approved antiviral agent, is a popular homeopathic commercial product. In select in vivo and in vitro observational studies, the drug showed a measureable innate immune therapeutic efficacy. The focus of the present study was to evaluate the innate and adaptive immunomodulatory effects of oral Engystol((r)) (1 or 10 tablets/L water consumed), prior to and post antigenic challenge in a mouse model with a well-characterized and clinically measureable immune system. We first evaluated the murine immune response when oral Engystol((r)) was given alone for 28days. Mice were then challenged with an antigen-specific H5N1 HA vaccine while on Engystol((r)) for an additional 33days. Serum and supernatants from cultured splenic lymphocytes were collected and screened with a 32-cytokine panel. Serum vaccine epitope-specific IgG titers plus T cell and B cell phenotypes from splenic tissue were also evaluated. Preliminary results showed that Engystol((r)) alone did not alter immunity; however, upon vaccine challenge, Engystol((r)) decreased CD4(+)/CD8(+) ratios, altered select cytokines/chemokines, and anti-H5N1 HA IgG titers were increased in the 10 tablet/L group. Collectively, these data suggest that Engystol((r)) can modulate immunity upon antigenic challenge. PMID- 27551986 TI - Characterization of a manganese peroxidase from white-rot fungus Trametes sp.48424 with strong ability of degrading different types of dyes and polycyclic aromatic hydrocarbons. AB - Manganese peroxidase, MnP-Tra-48424, was purified and characterized from the white-rot fungus Trametes sp.48424. MnP-Tra-48424 was strongly resistant to metal ions such as Ni2+, Li+, Ca2+, K+, Mn2+. MnP-Tra-48424 was also resistant to organic solvents such as propanediol, glycerol, and glycol. MnP-Tra-48424 decolorized dyes (indigo, anthraquinone, azo and triphenylmethane) and degraded different polycyclic aromatic hydrocarbons (PAHs). Indigo Carmine, Remazol Brilliant Blue R, Remazol Brilliant Violet 5R and Methyl Green were efficiently decolorized by MnP-Tra-48424. MnP-Tra-48424 also decolorized Indigo Carmine and Methyl Green combined with metal ions and organic solvents. The decolorization capability of MnP-Tra-48424 was not inhibited by selected metal ions and organic solvents. A combination of MnP-Tra-48424 and Lac-Tra-48424 improved the decolorization rate. In addition to dyes, MnP-Tra-48424 was effective at degrading individual PAHs (fluorene, fluoranthene, pyrene, phenanthrene, anthracene) and also PAHs in mixtures. PMID- 27551987 TI - Urban heat islands in China enhanced by haze pollution. AB - The urban heat island (UHI), the phenomenon of higher temperatures in urban land than the surrounding rural land, is commonly attributed to changes in biophysical properties of the land surface associated with urbanization. Here we provide evidence for a long-held hypothesis that the biogeochemical effect of urban aerosol or haze pollution is also a contributor to the UHI. Our results are based on satellite observations and urban climate model calculations. We find that a significant factor controlling the nighttime surface UHI across China is the urban-rural difference in the haze pollution level. The average haze contribution to the nighttime surface UHI is 0.7+/-0.3 K (mean+/-1 s.e.) for semi-arid cities, which is stronger than that in the humid climate due to a stronger longwave radiative forcing of coarser aerosols. Mitigation of haze pollution therefore provides a co-benefit of reducing heat stress on urban residents. PMID- 27551988 TI - Temporal Dynamics of Health and Well-Being: A Crowdsourcing Approach to Momentary Assessments and Automated Generation of Personalized Feedback. AB - OBJECTIVE: Recent developments in research and mobile health enable a quantitative idiographic approach in health research. The present study investigates the potential of an electronic diary crowdsourcing study in the Netherlands for (1) large-scale automated self-assessment for individual-based health promotion and (2) enabling research at both the between-persons and within persons level. To illustrate the latter, we examined between-persons and within persons associations between somatic symptoms and quality of life. METHODS: A website provided the general Dutch population access to a 30-day (3 times a day) diary study assessing 43 items related to health and well-being, which gave participants personalized feedback. Associations between somatic symptoms and quality of life were examined with a linear mixed model. RESULTS: A total of 629 participants completed 28,430 assessments, with a mean (SD) of 45 (32) assessments per participant. Most participants (n = 517 [82%]) were women and 531 (84%) had high education. Almost 40% of the participants (n = 247) completed enough assessments (t = 68) to generate personalized feedback including temporal dynamics between well-being, health behavior, and emotions. Substantial between person variability was found in the within-person association between somatic symptoms and quality of life. CONCLUSIONS: We successfully built an application for automated diary assessments and personalized feedback. The application was used by a sample of mainly highly educated women, which suggests that the potential of our intensive diary assessment method for large-scale health promotion is limited. However, a rich data set was collected that allows for group-level and idiographic analyses that can shed light on etiological processes and may contribute to the development of empirical-based health promotion solutions. PMID- 27551989 TI - Socioeconomic Adversity, Negativity in the Parent Child-Relationship, and Physiological Reactivity: An Examination of Pathways and Interactive Processes Affecting Young Children's Physical Health. AB - OBJECTIVE: We tested the hypothesis that socioeconomic status (SES) would predict children's physical health problems at the end of kindergarten among children whose parent reported greater parent-child relationship (PCR) negativity and/or who exhibited greater parasympathetic (RSA) reactivity. We also tested whether RSA and PCR negativity mediated the SES-health association. METHODS: Data were collected from 338 children (mean [SD] age, 5.32 [.32] years) and their primary caregivers (87% biological mothers) during the fall and subsequent spring of kindergarten. In the fall, parents reported income and education level (SES) and PCR negativity, and RSA reactivity was assessed via a standardized challenge protocol for young children. In the fall and then spring, parents reported children's chronic medical conditions and physical health impairments. Multivariate regression was conducted within a structural equation-modeling framework to test hypotheses. RESULTS: Significant interactions were found between SES and PCR negativity (b = -0.074, p = .035) and between SES and RSA reactivity (b = 0.169, p = .019) as predicts children's spring health impairment, adjusting for health in the preceding fall. Lower SES was associated with greater health impairment among children whose parents reported more PCR negativity (b = 0.110, p = .024) and children who showed greater RSA reactivity (b = -0.106, p = .011). Socioeconomic status was unrelated to physical health at low PCR negativity or RSA reactivity. Mediation models were not supported. CONCLUSION: Parent-child relationship quality and individual differences in stress reactivity may modulate the influence of SES on physical health in childhood. PMID- 27551990 TI - The Effect of Light-Intensity Cycling on Mood and Working Memory in Response to a Randomized, Placebo-Controlled Design. AB - OBJECTIVE: Prior attempts to measure psychological responses to exercise are potentially limited by a failure to account for participants' expectations, the absence of a valid exercise placebo, and demand characteristics. The purpose of this study was to explore the main and interactive effects of a manipulation designed to increase expectations about the psychological benefits of an acute bout of active, light-intensity (treatment), and passive (placebo) cycling on mood and cognition. Demand characteristics were attenuated during recruitment, informed consent, and interactions with test administrators by communicating to participants that the study purpose was to assess the effects of active and passive cycling on respiration, heart rate, and muscle activation. METHODS: A repeated-measures, randomized, placebo-controlled design (n = 60) was used with cycling (active, passive) and information (informed, not informed) as between subjects factors. State anxiety, feelings of energy, and working memory (percent accuracy and reaction time for correct responses) were measured at baseline (time 1), immediately after cycling (time 2) and 20 minutes after cycling (time 3). RESULTS: Most participants did not guess the purpose of the study (~92%) or expect a reduction in state anxiety (85%) or an increase in energy (80%) or cognitive performance (~93%). Mood and cognitive performance were not improved by active or passive cycling (all p values >= .12). CONCLUSIONS: The methods used here to disguise the experimental hypotheses provide a potential framework for reducing demand characteristics and placebo responses in future investigations of psychological responses to exercise. PMID- 27551992 TI - Engaging adolescent girls in transactional sex through compensated dating. AB - Transactional sex through so-called compensated dating in adolescent girls is a problem in need of public concern. Compensated dating typically involves the use of information communication technology to advertise, search, bargain, and eventually arrange for transactional sex. The technology enables the sexual partners to maintain privacy and secrecy in transactional sex. Such secrecy necessitates the girls' disclosure about their life experiences in order to address the concern. The disclosure is the focus of the present qualitative study of 27 girls practicing the dating in Hong Kong, China. Based on the disclosure, the study presents a grounded theory that epitomizes engagement in compensated dating by referential choice. Such a referential choice theory unravels that choice with reference to the family push and social norms sustains the engagement. Meanwhile, the choice rests on expectancy and reinforcement from experiential learning about compensated dating. The theory thus implies ways to undercut the engagement through diverting the referential choice of the dating. PMID- 27551991 TI - Replication of the Association of BDNF and MC4R Variants With Dietary Intake in the Diabetes Prevention Program. AB - OBJECTIVE: Genomewide association studies (GWAS) have identified consistent associations with obesity, with a number of studies implicating eating behavior as a primary mechanism. Few studies have replicated genetic associations with dietary intake. This study evaluates the association between obesity susceptibility loci and dietary intake. METHODS: Data were obtained as part of the Diabetes Prevention Program (DPP), a clinical trial of diabetes prevention in persons at high risk of diabetes. The association of 31 genomewide association studies identified obesity risk alleles with dietary intake, measured through a food frequency questionnaire, was investigated in 3,180 participants from DPP at baseline. RESULTS: The minor allele at BDNF, identified as protective against obesity, was associated with lower total caloric intake (beta = -106.06, SE = 33.13; p = .0014) at experimentwide statistical significance (p = .0016), whereas association of MC4R rs571312 with higher caloric intake reached nominal significance (beta = 61.32, SE = 26.24; p = .0194). Among non-Hispanic white participants, the association of BDNF rs2030323 with total caloric intake was stronger (beta = -151.99, SE = 30.09; p < .0001), and association of FTO rs1421085 with higher caloric intake (beta = 56.72, SE = 20.69; p = .0061) and percentage fat intake (beta = 0.37, SE = 0.08; p = .0418) was also observed. CONCLUSIONS: These results demonstrate with the strength of independent replication that BDNF rs2030323 is associated with 100 to 150 greater total caloric intake per allele, with additional contributions of MC4R and, in non Hispanic white individuals, FTO. As it has been argued that an additional 100 kcal/d could account for the trends in weight gain, prevention focusing on genetic profiles with high dietary intake may help to quell adverse obesity trends. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov,NCT00004992. PMID- 27551993 TI - Measuring positive and negative aspects of youth behavior: Development and validation of the Adolescent Functioning Scale. AB - This paper outlines the development and validation of the Adolescent Functioning Scale (AFS) in an Australian sample of parents of young people aged 11-18 years (N = 278). The AFS, a parent self-report measure, was designed to assess problem behavior and positive development in adolescents. Principal components analysis produced a 33-item measure comprising four subscales: Positive Development, Oppositional Defiant Behavior, Antisocial Behavior and Emotional Difficulties. Convergent validity was established via correlations between the AFS and established measures of adolescent functioning and parenting, and discriminant validity was shown through no association between the AFS and a measure of technology use. Internal consistency for the subscales was high (H = .82-.92 for different age groups), as was test-retest reliability (r = .77-.86). The study indicated that the AFS is a potentially valuable tool for assessing levels of problem behaviors and positive development in adolescents. PMID- 27551994 TI - An easy and sensitive sandwich assay for detection of Mycobacterium tuberculosis Ag85B antigen using quantum dots and gold nanorods. AB - Mycobacterium tuberculosis is a serious global infectious pathogen causing tuberculosis (TB). The development of an easy and sensitive method for the detection of M. tuberculosis is in urgent need due to complex and low specificity of the current assays. Herein, we present a novel method for M. tuberculosis detection based on a sandwich assay via antigen-antibody interaction using silica coated quantum dots (SiQDs) and gold nanorods (AuNRs). A genetically engineered recombinant antibody (GBP-50B14 and SiBP-8B3) was bound to surfaces of AuNRs and SiQDs respectively, without any surface modification. The antigen-antibody interaction was revealed using M. tuberculosis-specific secretory antigen, Ag85B. Two biocomplexes showed a quenching effect in the presence of the target antigen through a sandwich assay. The assay response was in the range of 1*10-3-1*10 10MUgmL-1 (R=0.969) and the limit of detection for Ag85B was 13.0pgmL-1. The Ag85B was selectively detected using three different proteins (CFP10, and BSA), and further specifically confirmed by the use of spiked samples. Compared with existing methods, a highly sensitive and selective method for Ag85B-expressing M. tuberculosis detection has been developed for better diagnosis of TB. PMID- 27551995 TI - Dendritic structure DNA for specific metal ion biosensor based on catalytic hairpin assembly and a sensitive synergistic amplification strategy. AB - In this work, a sensitive electrochemical biosensing to Pb2+ was proposed based on the high specificity of DNAzymes to Pb2+. The response signal was efficiently amplified by the catalytic hairpin assembly induced by strand replacement reaction and the formation of dendritic structure DNA (DSDNA) by layer-by-layer assembly. Firstly, in the presence of Pb2+, the substrate strand (S1) of the Pb2+ specific DNAzymes was specifically cleaved by Pb2+. Secondly, one of the two fragments (rS1) introduced into the electrode surface was hybridized with a hairpin DNA (H1) and further replaced by another hairpin DNA (H2) by the hybridization reaction of H1 with H2. The released rS1 then induced the next hybridization with H1. After repeated cycles, the catalytic recycling assembly of H2 with H1 was completed. Thirdly, two bioconjugates of Pt@Pd nanocages (Pt@PdNCs) labeled with DNA S3/S4 and electroactive toluidine blue (Tb) (Tb-S3 Pt@PdNCs and Tb-S4-Pt@PdNCs) were captured onto the resultant electrode surface through the hybridization of S3 and H2, S3 and S4, resulting in the formation of DSDNA triggered by layer-by-layer assembly. This formed DSDNA greatly facilitated the immobilization of manganese(III) meso-tetrakis (4-N-methylpyridiniumyl) porphyrin (MnTMPyP) as mimicking enzyme. Under the synergistic catalysis of Pt@PdNCs and MnTMPyP to H2O2 reduction, the effective signal amplification of the developed Pb2+ biosensor was achieved. As a result, the sensitive detection of the proposed electrochemical strategy for Pb2+ was greatly improved in the range of 0.1pM-200nM with a detection limit of 0.033pM. PMID- 27551996 TI - High sensitive and selective electrochemical biosensor: Label-free detection of human norovirus using affinity peptide as molecular binder. AB - Norovirus is known as the major cause of highly infection for gastrointestinal tracts. In this study, robust and highly sensitive biosensors for detecting human norovirus by employing a recognition affinity peptide-based electrochemical platform were described. A series of amino acid-substituted and cysteine incorporated recognition peptides isolated from evolutionary phage display technique was chemically synthesized and immobilized to a gold sensor layer, the detection performance of the gold-immobilized synthetic peptide-based sensor system was assessed using QCM, CV and EIS. Using EIS, the limit of detection with Noro-1 as a molecular binder was found to be 99.8nM for recombinant noroviral capsid proteins (rP2) and 7.8copies/mL for human norovirus, thereby demonstrating a high degree of sensitivity for their corresponding targets. These results suggest that a biosensor which consists of affinity peptides as a molecular binder and miniaturized microdevices as diagnostic tool could be served as a new type of biosensing platform for point-of-care testing. PMID- 27551997 TI - 2-Aminopurine-modified DNA homopolymers for robust and sensitive detection of mercury and silver. AB - Heavy metal detection is a key topic in analytical chemistry. DNA-based metal recognition has advanced significantly producing many specific metal ligands, such as thymine for Hg2+ and cytosine for Ag+. For practical applications, however, robust sensors that can work in a diverse range of salt concentrations need to be developed, while most current sensing strategies cannot meet this requirement. In this work, 2-aminopurine (2AP) is used as a fluorescence label embedded in the middle of four 10-mer DNA homopolymers. 2AP can be quenched up to 98% in these DNA without an external quencher. The interaction between 2AP and all common metal ions is studied systematically for both free 2AP base and 2AP embedded DNA homopolymers. With such low background, Hg2+ induces up to 14-fold signal enhancement for the poly-T DNA, and Ag+ enhances up to 10-fold for the poly-C DNA. A detection limit of 3nM is achieved for both metals. With these four probes, silver and mercury can be readily discriminated from the rest. A comparison with other signaling methods was made using fluorescence resonance energy transfer, graphene oxide, and SYBR Green I staining, respectively, confirming the robustness of the 2AP label. Detection of Hg2+ in Lake Huron water was also achieved with a similar sensitivity. This work has provided a comprehensive fundamental understanding of using 2AP as a label for metal detection, and has achieved the highest fluorescence enhancement for non-protein targets. PMID- 27551998 TI - A contemporary approach for design and characterization of fiber-optic-cortisol sensor tailoring LMR and ZnO/PPY molecularly imprinted film. AB - A fiber optic salivary cortisol sensor using a contemporary approach of lossy mode resonance and molecular imprinting of nanocomposites of zinc oxide (ZnO) and polypyrrole (PPY) is structured and depicted for the concentration range of 0-10 6g/ml of cortisol prepared in artificial saliva. Components of polymer preparation and the nanocomposite of polymer with ZnO are optimized for realizing the molecular imprinted layer of the sensor. Nanocomposite having 20% of ZnO in PPY is found to give highest sensitivity of the sensor. The sensor reports the best limit of detection ever reported with better stability, repeatability and response time. Lossy mode resonance based salivary cortisol sensor using nanocomposite molecular imprinted layer reported first time boosts the specificity of the sensor. The implementation of sensor over optical fiber adds up other advantages such as real time and online monitoring along with remote sensing abilities which makes the sensor usable for nonintrusive clinical applications. PMID- 27551999 TI - Highly sensitive surface-enhanced Raman scattering detection of hexavalent chromium based on hollow sea urchin-like TiO2@Ag nanoparticle substrate. AB - As one of the most toxic heavy metals, hexavalent chromium (Cr(VI)) has long been a concern due to its threats to human health and the environment. In this work, we develop a sensitive surface-enhanced Raman scattering (SERS) sensor for highly specific detection of Cr(VI) using hollow sea urchin-like TiO2@Ag nanoparticles (NPs). The TiO2@Ag NPs are functionalized with glutathione (GSH) and used as substrates with 2-mercaptopyridine (2-MPy) as a Raman reporter for a recyclable SERS-active sensor, enabling ultrasensitive detection of Cr(VI). Excellent SERS signals of 2-MPy reporters are detected when GSH complexation with Cr(VI) causes aggregation of the TiO2@Ag NPs. The developed sensor exhibits good linearity in the range from 10nM to 2MUM for Cr(VI) with a detection limit of ca. 1.45nM. It features excellent selectivity to Cr(VI) over other interfering metal ions, and good application for quantitative analysis of Cr(VI) in water samples. Moreover, the proposed SERS sensor can be fully regenerated when exposed to UV light as a result of the self-cleaning ability of the substrates. In contrast to the traditional SERS detection, the present work shed new light on the design and synthesis of hierarchically self-assembled 3D substrate for SERS, catalysis and biosensor development. PMID- 27552000 TI - The effect of low-carbohydrates calorie-restricted diet on visceral adipose tissue and metabolic status in psoriasis patients receiving TNF-alpha inhibitors: results of an open label controlled, prospective, clinical study. AB - OBJECTIVE: TNF alpha inhibitors are usually associated with anthropometric changes over the time, however whether and how the visceral adipose tissue (VAT) is involved in this phenomenon, still remains unclear. Aim of the study is to evaluate if the increases in trunk fat percentage (TF%) and VAT are directly involved in anthropometric changes occurring during treatment, and whether and how a calorie restricted diet could prevent these changes. MATERIAL AND METHODS: Twenty patients receiving TNF-alpha inhibitors for psoriasis was evaluated at baseline (T0) and after 24 weeks of therapy (T24), and then compared with 25 patients receiving a combined treatment based on TNF alpha inhibitors and low carbohydrates calorie-restricted diet. RESULTS: TNF-alpha inhibitors do not influence the VAT expression. The combined treatment is associated with a significant decrease in body weight (kg) (p < .0001), BMI (p = .0001), WC (cm) (p < .0001), TF% (p < .0001), VAT (p < .0001), serum levels of triglycerides (mg/dL) (p = .0018) and total cholesterol (mg/dL) (p = .0005). CONCLUSIONS: The administration of TNF-alpha inhibitors can induce anthropometric changes after 24 weeks, but it does not cause an increase in VAT. The association between low carbohydrates calorie-restricted diet and anti-TNF-alpha therapy seems to be able to improve the anthropometric profile of psoriasis patients. PMID- 27552001 TI - Rational Design of Dipolar Chromophore as an Efficient Dopant-Free Hole Transporting Material for Perovskite Solar Cells. AB - In this paper, an electron donor-acceptor (D-A) substituted dipolar chromophore (BTPA-TCNE) is developed to serve as an efficient dopant-free hole-transporting material (HTM) for perovskite solar cells (PVSCs). BTPA-TCNE is synthesized via a simple reaction between a triphenylamine-based Michler's base and tetracyanoethylene. This chromophore possesses a zwitterionic resonance structure in the ground state, as evidenced by X-ray crystallography and transient absorption spectroscopies. Moreover, BTPA-TCNE shows an antiparallel molecular packing (i.e., centrosymmetric dimers) in its crystalline state, which cancels out its overall molecular dipole moment to facilitate charge transport. As a result, BTPA-TCNE can be employed as an effective dopant-free HTM to realize an efficient (PCE ~ 17.0%) PVSC in the conventional n-i-p configuration, outperforming the control device with doped spiro-OMeTAD HTM. PMID- 27552002 TI - The health needs and healthcare experiences of young people trafficked into the UK. AB - Young people who have been trafficked may have experienced significant trauma and violence but little is known about their health and healthcare needs. This UK study aimed to address that gap. It included a health survey and qualitative interviews with 29 young people aged 16-21 trafficked into the UK from other countries who were recruited through voluntary organisations and children's social services. These data were supplemented by interviews with relevant professionals. Over half the young people had been trafficked for sex work but sexual violence had also been experienced by those trafficked for domestic servitude and labour exploitation. Physical violence, threats, restrictions of liberty and deprivation were also widespread, as were experiences of physical and sexual violence prior to being trafficked. Five young women had become pregnant whilst trafficked; three were parents when interviewed. Two-thirds screened positive for high levels of psychological distress, including PTSD. Twelve reported suicidal thinking. Whilst some were keen for opportunities to talk to health professionals confidentially and wanted practitioners to treat their accounts as credible, others wanted to forget abusive experiences. Complex gatekeeping systems, language barriers and practitioners who failed to take them seriously limited access to healthcare. Support and advocacy were helpful in assisting these young people to navigate healthcare systems. Health professionals need to recognise and respond appropriately to trafficked young people's often complex mental health needs and refer them to relevant services, as well as facilitating care at later times when they might need support or be more ready to receive help. PMID- 27552004 TI - [Concepcion inventory: Development of a screening instrument for depression in primary care in Chile]. AB - BACKGROUND: Screening instruments are required for the detection of depressive disorders by primary care practitioners. AIM: To develop a screening instrument to detect depression, based on data gathered interviewing patients attending primary health care settings. MATERIAL AND METHODS: The instrument was constructed with data about factors associated or triggering a depressive disorder obtained from 3,000 patients consulting for general morbidity. All patients answered the Composite International Diagnostic Interview, (version 2.1, section depression) and an inventory containing 39 risk factors for depression, obtained from the literature. A multiple imputation method using chained equations was carried out. Using a binary logistic regression with backward selection, an equation for depression screening was obtained. The c-index was calculated to estimate discriminating power of the model. A shrinkage factor was estimated to adjust the predictive model. RESULTS: Estimations were carried out with data from 2,552 patients with a median age of 47 years (73% women). Fifty five percent lived with a partner and 45% had basic studies. The method selected 14 significant predictors, with a shrinkage value of 0.861 and a c-index of 0.838 (95% confidence intervals 0.82-0.86). CONCLUSIONS: The instrument has adequate psychometric properties as a screening tool for depression in primary health care. PMID- 27552003 TI - Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges. AB - INTRODUCTION: The use of antiretroviral therapy (ART) in pregnancy to prevent vertical HIV transmission has been one of the most successful public health programs in the last decade. As a result, an unprecedented number of women are taking ART at conception and during pregnancy. Given few randomized studies evaluating safety of different ART regimens in pregnancy, ongoing drug safety surveillance is critical. Areas covered: This review aims to provide a rationale for ART drug safety surveillance, describe changing patterns of ART use and summarize current surveillance efforts in both low-resource and high-resource settings. Additionally, biostatistical approaches to and challenges in analysis of observational surveillance data are discussed. Expert opinion: The global landscape of ART use in pregnancy is rapidly increasing and evolving. Any increase in adverse effects of in-utero exposure to ART has the potential to reduce the impact of improvements in infant morbidity and mortality gained from decreased vertical HIV transmission. ART drug safety surveillance should therefore be a critical piece of programs to prevent mother to child transmission in both high- and low-resource settings. Current surveillance efforts could be strengthened with long-term follow-up of exposed children, pooling of data across cohorts and standardized approaches to analysis. PMID- 27552005 TI - [Mental health and stress by acculturation in immigrants from South America in northern Chile]. AB - BACKGROUND: Coping with changes brought about by immigration and social circumstances that often characterize this process may cause mental health problems. AIM: To analyze the relationship between acculturation stress and mental health symptoms in South American immigrants residing in Antofagasta, Chile. MATERIAL AND METHODS: The OQ questionnaire, which assesses mental health and the acculturation stress questionnaire from Ruiz, were answered by 431 immigrants (53.8% Colombian and 46.2% Peruvian) aged between 18 and 65 years old. RESULTS: The major source of acculturation stress was distance from origin, followed by difficulties in social relationships and perceived discrimination and rejection. About 50% of respondents had elevated levels of discomfort in their life, with mental health problems derived from their adjustment to social roles and relationships. There was a high correlation between acculturation stress levels and severity of mental health symptoms. CONCLUSIONS: Immigrants are exposed to high levels of stress resulting in a negative impact on their mental health. PMID- 27552006 TI - [Hospital discharges due to stroke in the period 2001-2010 in a southern Chilean region]. AB - BACKGROUND: Stroke is the most common specific cause of death in Chile since 2008, representing roughly 10% of total deaths in the country. AIM: To analyze hospital discharges with a diagnosis of stroke in the period 2001-2010 in a regional Chilean health service. MATERIAL AND METHODS: Analysis of hospital discharge databases of the department of statistics and health information (DEIS) of the Chilean Ministry of Health for the years 2001-2010. All subjects aged over 15 years and discharged with a diagnosis of stroke during the period 2001-2010 in a southern Chilean region, were included in the study. RESULTS: In the period, 6,548 hospital discharges due to stroke were registered. The most common diagnoses were ischemic and hemorrhagic stroke, followed by intracranial hemorrhage. Hospital stay fluctuated between one and ten days in 77% of patients. The incidence rate of stroke as a discharge diagnosis was 961.3 per 100,000 population per year (95% Confidence intervals 950.7- 972.4). CONCLUSIONS: The information collected allows updating the information regarding hospital discharges due to stroke in the region studied. PMID- 27552007 TI - [The legal framework to prevent teenage pregnancies]. AB - BACKGROUND: There are legal regulations about sexual and reproductive rights of adolescents. However, this legal framework (LF) may have contradictory elements: there are laws assuring confidentiality and access to contraception at any age but there are other laws that consider any sexual contact with an adolescent younger than 14 a sexual assault, whose report to the legal authorities in mandatory. AIM: To explore the knowledge and clinical practice of primary health care (PHC) providers regarding prevention of teenage pregnancy. MATERIAL AND METHODS: Qualitative study collecting data using semi-structured interviews made to midwives and directors of PHC centers. Analysis of the data was based on Grounded Theory. RESULTS: There is a differentiated clinical care for pregnancy prevention among adolescents if they are over 14 years old. This is due to the LF, specifically to the sexual crime?s law (19,927) and the law about regulation of the fertility (20,418). The differences affect health care, access and counseling about contraception and confidentiality. Healthcare of teenagers under the age of 14 is perceived as problematic for providers, due to the possible legal implications. CONCLUSIONS: The LF causes insecurity on health care providers and derives in a differentiated clinical approach according to the patient's age. This is a barrier to provide timely and confidential access to counseling and contraception. PMID- 27552009 TI - [Khorama score as a predictive tool for thromboembolic events in high risk patients]. AB - BACKGROUND: There is an established relation between cancer and the development of thromboembolic venous disease. Khorana et al developed a predictive score using clinical characteristics and laboratory values to stratify patients according to their risk. AIM: To characterize using Khorana score, patients with active cancer and a diagnosis of thromboembolic disease during hospitalization in an oncology hospital. MATERIAL AND METHODS: Review of records of the pharmacy of the hospital, selecting patients who received heparin in therapeutic doses during their hospitalization. Using laboratory values available in the medical records, the Khorama score was calculated. RESULTS: Twenty seven patients with thromboembolic events, aged 60 +/- 2 years (56% males) were selected for the study. Eighty percent of them were catalogued in the intermediate and high risk group according to Khorana score. CONCLUSIONS: Khorana score is a simple scale that might be useful to establish early prophylactic measures in patients with high risk for thromboembolic events, especially those with cancer. PMID- 27552008 TI - [Perception of users about an Integral Model of Family and Community Health care in Santiago, Chile]. AB - BACKGROUND: The integral Model of Family and Community Health care is based on three essential principles: patient centered care, comprehensive care and continuity of care. AIM: To know the perception of primary care clinic users about the elements that should be considered in a patient centered integrated health care. MATERIAL AND METHODS: Ten males and 31 females aged 18 to 78 years, users of two public family primary care centers participated in focus groups, which were recorded. A qualitative descriptive research design based on content analysis according to Krippendorf was done. RESULTS: Seven issues emerged from the description of patients? experiences: professional-patient relationship, fragmentation of care, continued care with the same professional, promotion and prevention, availability of services and patient records. CONCLUSIONS: There are difficulties to install an integral model of family and community health care. The concerns raised by participants should be considered in order to modify the design of these models. PMID- 27552010 TI - [Association between handgrip strength and functional performance in Chilean older people]. AB - BACKGROUND: Handgrip strength is an important predictor of functional performance among older adults. AIM: To measure handgrip strength in older adults and relate its values to their clinical functional assessment. MATERIAL AND METHODS: Handgrip strength was measured in 1047 older adults living in the community and aged 71.9 +/- 7 years (740 and 307 females). The values obtained were grouped by age, gender and functional condition. The latter was assessed using a score validated in Chile (Functional Assessment of Older Adults or EFAM), that classifies participants as autonomous without risk, autonomous in risk and in risk of becoming non-autonomous. RESULTS: In women, hand grip strength values were 17.4 +/- 5.6 and 18.7 +/- 5.7 kg for left and right hand; figures for men were 30.6 +/- 7.8 and 31.8 +/- 8.3 kg, respectively. According the functional assessment, the figures for autonomous without risk, autonomous with risk and with risk of becoming non-autonomous participants, were 23.5 +/- 9.7, 21.8 +/- 9.1 and 19.3 +/- 8.2 respectively. CONCLUSIONS: There is an association between the degrees of functional performance of older people and handgrip strength. PMID- 27552011 TI - [Validation of the short assessment of health literacy for spanish-speaking adults test in Chile]. AB - BACKGROUND: Health literacy is defined as the degree to which individuals obtain, process and understand basic health information and services. It is necessary to make appropriate decisions about their health. Evidence has shown that the level of health literacy is critical to the prognosis of chronic diseases. The Short Assessment of Health Literacy for Spanish-speaking Adults (SAHLSA-50) is a short and simple health literacy adult assessment. AIM: To determine the validity and reliability indicators of SAHLSA-50 in Chilean adults. MATERIAL AND METHODS: The survey was applied to 84 older adults living in high and low income neighborhoods. RESULTS: The survey had an adequate construct validity and reliability, its Comparative Fit Index was 0.93, its Tucker-Lewis index was 0.927 and its Root Mean Square Error of Approximation was 0.044. ?Close fit? was not statistically significant (p = 0.828). Reliability was estimated by K-Richardson, which reported a good outcome (0.9255). Despite the good global indicators obtained, it is necessary to pay attention to some items that would fail to explain the ?Health literacy? construct or were beyond the parameters of difficulty and discrimination proposed by the authors of the test. CONCLUSIONS: We propose this test as a useful tool to assess health literacy in the adult population in Chile. Its use and incorporation into local research can be especially recommended in the areas of education and health promotion. PMID- 27552012 TI - [Hypovitaminosis D in Children with Hashimoto?s Thyroiditis]. AB - BACKGROUND: Vitamin D deficiency or insufficiency may play a role in the pathogenesis of certain autoimmune diseases. AIM: To measure vitamin D levels in children with Hashimoto?s thyroiditis (HT) (either with subclinical or marked hypothyroidism) and in healthy controls. MATERIAL AND METHODS: We included 68 children with HT aged 12 +/- 4 years (39 females) from a pediatric outpatient clinic and 68 healthy children aged 10 +/- 4 years (37 females). Calcium metabolism parameters, thyroid function tests and anti-thyroid peroxidase (anti TPO), anti-thyroglobulin (anti-TG) and 25 hydroxy vitamin D (25OHD) levels were measured. RESULTS: Patients were older than controls but well matched by gender distribution. Mean 25OHD levels were significantly lower in HT patients than controls (16.8 +/- 9.3 and 24.1 +/- 9.4 ng/mL respectively, P < 0.01). Frequency of vitamin D deficiency was 76 and 35% in HT patients and controls, respectively (P < 0.001). CONCLUSIONS: Vitamin D deficiency is more common in children with HT than healthy controls. PMID- 27552013 TI - [Simulated patients in health care training: the human side of simulation]. AB - Simulated patients (SP) are now used in the majority of the institutions that train health care professionals in patient-centered care. This article summarizes the information about the use of SP in health education using information from the literature and from the 15 years? experience in the medical school of the Pontificia Universidad Catolica de Chile. It describes the different definitions in use, the roles and scenarios that can be used when teaching with SP and the organization that any institution working with SP should have in order to promote the optimal use of SP. Working with SP allows faculty to center their teaching on their students while keeping the focus on the patient. Students appreciate learning with SP and particularly value feedback from the patients? perspective. PMID- 27552014 TI - [Body dysmorphic disorder: clinical aspects, nosological dimensions and controversies with anorexia nervosa]. AB - There is strong evidence about the co-existence of body dysmorphic disorder (BDD) and eating disorders (ED), particularly with anorexia nervosa (AN). An exhaustive review of the specialised literature regarding these disorders was carried out. The results show that their co-occurrence implies a more complex diagnosis and treatment, a more severe clinical symptomatology and a worse prognosis and outcome. Both disorders display common similarities, differences and comorbidities, which allow authors to classify them in different nosological spectra (somatomorphic, anxious, obsessive-compulsive, affective and psychotic). Their crossover involves higher levels of body dissatisfaction and body image distortion, depression, suicidal tendency, personality disorders, substance use/abuse, obsessive-compulsive disorder, social phobia, alexithymia and childhood abuse or neglect background. Treatment including cognitive-behavioral psychotherapy and selective reuptake serotonin inhibitors are effective for both, BDD and ED; nevertheless, plastic surgery could exacerbate BDD. Clinical traits of BDD must be systematically detected in patients suffering from ED and vice versa. PMID- 27552015 TI - [Red cell distribution width as a risk marker in patients with cardiovascular diseases]. AB - Red cell distribution width (RDW) is a measurement of the variation in size, as well as an index of heterogeneity of erythrocytes, which is used in combination with other hematologic parameters as an aid to the differential diagnosis of hypochromic anemia. RDW could also serve as a biomarker in the diagnosis and prognosis patients with cardiovascular diseases. However, it is unclear whether the increased heterogeneity is the cause or consequence of other pathophysiological conditions such as renal failure, malnutrition, inflammation and oxidative stress, which among other conditions are actively involved in the genesis and progression of cardiovascular diseases. The aim of this review is to show and discuss recent evidence about the role of RDW measurement as an aid in the diagnosis and prognosis of patients with such diseases. Besides being a simple, inexpensive and routinely measured parameter, it could help in the stratification of patients according to their risk in clinical practice. PMID- 27552016 TI - [Management of psychological trauma in primary care]. AB - Exposure to traumatic events is frequent in the general population and psychiatric sequelae such as post-traumatic stress disorders are common. The symptoms of psychiatric sequelae after trauma are vague, with multiple psychological and physical symptoms, which can confuse the health care professional. This paper seeks to facilitate the work in primary care, providing practical information about the diagnosis, initial management and referral of patients who have suffered traumatic experiences. Some early interventions and treatments are suggested. PMID- 27552017 TI - [Quality assurance of medical practice in Chile: Mandatory approval of the National Board Examination in Medicine as a quality assurance to start medical practice]. PMID- 27552018 TI - [Association between the decline in global fertility rate and the incorporation of women to the workforce]. AB - BACKGROUND: The global fertility rate (GFR) is defined as the mean number of children that a woman could have in a hypothetical cohort, not exposed to death during the fertile period. GFR has fallen from 3.4 to 1.9 children per women in the period 1970-2010. AIM: To explore the relationship between the fall in GFR and the incorporation of women to work in the period 1960-2011. MATERIAL AND METHODS: Data from the National Statistics Institute was used. GRF was calculated using specific fertility rates for each year considering women aged 15 to 49 years. Work rates were obtained from yearly vital statistics reports. RESULTS: Between 1960 and 2011, GRF decreased from 5.5 to 1.9 in Chile. The first inflection occurred in 1970. In the same period, female workforce increased from 22.4 to 40.2%. CONCLUSIONS: To motivate the participation of female work-force without decrease the GRF allowing population replacement, it is suggested the need to create new public policies with benefits and support from the state. PMID- 27552019 TI - [Motivation and self-directed learning among medical students]. AB - BACKGROUND: Motivation is an essential aspect in the training process of medical students. The association that motivation can have with learning self-regulation is of utmost importance for the design of curriculum, teaching methods and evaluation. AIM: To describe the motivational aspects of self-directed learning among medical students from a traditional Chilean University. MATERIAL AND METHODS: A qualitative, descriptive study based on grounded theory of Strauss and Corbin. Twenty 4th and 5th year medical students were selected using a maximum variation sampling technique. After obtaining an informed consent, semi structured interviews and field notes were carried out. Data were analyzed to the level of open coding through Atlas-ti 7.5.2. RESULTS: From the student point of view, personal motivational aspects are linked to the search for information, constant updating, the perception of the physician-patient relationship and interest in subject matters. From the scope of teachers, a main issue is related to their ability to motivate students to develop independent study skills. CONCLUSIONS: Personal motivational aspects facilitate the development of independent study skills, specifically in the search of information. The role of teachers is crucial in promoting these skills and the perception of medical students from their learning process. PMID- 27552020 TI - [Laugier-Hunziker syndrome in a patient with Sjogren?s syndrome: Report of one case]. AB - Laugier-Hunziker syndrome is a rare benign idiopathic condition characterized by acquired macular pigmentation of lips and buccal mucosa, often accompanied with melanonychia. The main concern with this condition is to rule out other differential diagnosis with systemic repercussions and similar hyperpigmentation patterns, such as Peutz-Jeghers syndrome, adrenal insufficiency and melanoma. We report a 58-year-old female with a 20-year history of Sjogren?s syndrome, presenting with melanonychia and hyperpigmentation in the buccal mucosa. She had no relevant medication history and is a non-smoker. The patient denied any other symptoms. The histopathology confirmed the diagnosis of Laugier-Hunziker syndrome. PMID- 27552021 TI - [Pontine reversible leucopathy in an AIDS patient associated with highly active antiretroviral therapy (HAART): Report of one case]. AB - Posterior reversible encephalopathy (PRES) is a condition characterized by T2 and FLAIR hyperintensities in magnetic resonance imaging (MRI) studies, localized preferentially in the occipital-parietal white matter regions. Pathological MRI images located in midbrain, pons, medulla and spinal cord, that could be asymptomatic, were recently included in this entity. These images are interpreted as vasogenic edema, which is caused by arterial hypertension or eclampsia, neurotoxicity related to immunosuppressive agents or chemotherapy, among other causes. We report a 25 years old asymptomatic male with AIDS, with normal blood pressure who after initiating highly active antiretroviral therapy (HAART) reported vertigo. The MRI showed a central pontine T2 hyperintensity with diffusion restriction, which was interpreted as a central pontine myelinolysis (CPM), but the lack of motor symptoms made improbable a real demyelination of the pons. The follow-up MRI revealed complete regression of the images. To our knowledge, this case could be the second report of a reversible leucopathy of the pons in a patient with AIDS, were the MRI images also simulated a CPM. This report extends the knowledge around the variability of the pathogenic interpretation of CPM images and their association with HAART. PMID- 27552022 TI - [Correlational analysis for a brief version of RDQ: New analysis of Guic et al (2014)]. PMID- 27552023 TI - [Tobacco medical student at the National University of Caaguazu, May 2015]. PMID- 27552024 TI - [Using PowerPoint in class: Is it necessary to study it?]. PMID- 27552025 TI - [Scientific initiation scholarships: a comprehensive development model for Latin American research]. PMID- 27552026 TI - Respiratory Muscle Weakness and Respiratory Failure in Pediatric Neuromuscular Disorders: The Value of Noninvasive Determined Tension-Time Index. AB - Background In pediatric neuromuscular disorders (NMD), respiratory muscle weakness parallels respiratory failure. The objectives of this study are (1) to evaluate respiratory muscle capacity in neuromuscular children and (2) to assess the relationship between vital capacity, respiratory muscle performance, and alveolar ventilation during sleep and wakefulness. Methods Inspiratory vital capacity (IVC), peak inspiratory pressure (PIP), mouth occlusion pressure (P0.1), and noninvasive tension-time index of the respiratory muscles (TTImus) were studied in 80 NMD subjects (12.1 +/- 3.3 years) and 80 healthy children (11.1 +/- 2.2 years). Subjects' results were compared with arterial blood gases and polysomnography. Results In 15 NMD subjects with normal ventilation IVC and PIP were reduced to 70% predicted but TTImus was normal. In 50 NMD subjects with nocturnal hypoventilation IVC and PIP were lower than 50% predicted, TTImus was doubled compared with the control group. In 15 NMD subjects with diurnal and nocturnal hypoventilation IVC and PIP were below 30% predicted, TTImus was increased fourfold, and thus the main determinant of respiratory failure. Conclusions In NMD children, reduced IVC and PIP result in increased respiratory muscle load and disturbed ventilation. TTImus is an important noninvasive determinant of disturbed ventilation in children with NMD. PMID- 27552027 TI - Crossed Pontine Hemiatrophy Associated with Unilateral Cerebellar Hemorrhage in Premature Infants. AB - Background Cerebellar hemorrhage is a complication of extreme prematurity with a significant impact on the neurodevelopmental outcome. It has been shown that cerebellar hemorrhage is associated with a reduction in the anteroposterior diameter of the pons on the midline sagittal plane at term-equivalent age, suggesting that cerebellar injury may impair overall pons development in premature infants. Objective This study stemmed from an incidental observation of crossed pontine hemiatrophy in a preterm infant with a history of unilateral massive cerebellar bleeding. We aimed to verify the presence of this association in a population of preterm infants. Methods Among all, very preterm infants (GA < 32 weeks) born at our institution over a 6-year period, those with a diagnosis of unilateral massive cerebellar hemorrhage were selected. Magnetic resonance imaging scans of the selected subjects were reviewed. Results Six patients with unilateral massive cerebellar hemorrhage were identified. MRI showed crossed hemiatrophy of the pons in all cases. Conclusion Crossed hemiatrophy of the pons was associated with massive unilateral cerebellar hemorrhage. This finding may reflect retrograde degeneration of pontocerebellar fibers and loss of neurons in contralateral hemipons. PMID- 27552028 TI - Electret Polyvinylidene Fluoride Nanofibers Hybridized by Polytetrafluoroethylene Nanoparticles for High-Efficiency Air Filtration. AB - Airborne particulate matter (PM) pollution has become a severe environmental concern calling for electret fibrous materials with high filtration efficiency and low pressure drop. However, restraining the dissipation of the electric charges in service to ensure the stabilized electrostatic force of the fibers for effectively adsorbing particles is extremely important and also challenging. Herein, we report novel electret nanofibrous membranes with numerous charges and desirable charge stability using polyvinylidene fluoride (PVDF) as the matrix polymer and polytetrafluoroethylene nanoparticles (PTFE NPs) as an inspiring charge enhancer through the in situ charging technology of electrospinning. Benefiting from the employment of PTFE NPs and optimized injection energy, the fibrous membranes are endowed with elevated surface potentials from 0.42 to 3.63 kV and reduced decrement of charges from 75.4 to 17.5%, which contribute to the ameliorative stability of filtration efficiency. Significantly, an electret mechanism is proposed, while deepened depth of the energy level and incremental polarized dipole charges with increasing PTFE NP concentrations and injection energy have been confirmed through the measurement of open-circuit thermally stimulated discharge and surface potential decay. Ultimately, the resultant fibrous membrane exhibited a high filtration efficiency of 99.972%, a low pressure drop of 57 Pa, a satisfactory quality factor of 0.14 Pa(-1), and superior long-term service performance. The successful fabrication of such an intriguing material may provide a new approach for the design and development of electret materials for PM2.5 governance. PMID- 27552029 TI - Mobility of lysozyme in poly(l-lysine)/hyaluronic acid multilayer films. AB - The spatial and temporal control over presentation of protein-based biomolecules such as growth factors and hormones is crucial for in vitro applications to mimic the complex in vivo environment. We investigated the interaction of a model protein lysozyme (Lys) with poly(L-lysine)/hyaluronic acid (PLL/HA) multilayer films. We focused on Lys diffusion as well as adsorption and retention within the film as a function of the film deposition conditions and post-treatment. Additionally, an effect of Lys concentration on its mobility was probed. A combination of confocal fluorescence microscopy, fluorescence recovery after photobleaching, and microfluidics was employed for this investigation. Our main finding is that adsorption of PLL and HA after protein loading induces acceleration and reduction of Lys mobility, respectively. These results suggest that a charge balance in the film to a high extent governs the protein-film interaction. We believe that control over protein mobility is a key to reach the full potential of the PLL/HA films as reservoirs for biomolecules depending on the application demand. PMID- 27552030 TI - Perceived stress and fatigue among students in a doctor of chiropractic training program. AB - OBJECTIVE: High levels of stress and fatigue are associated with decreased academic success, well-being, and quality of life. The objective of this research was to quantify levels of perceived stress and fatigue among chiropractic students to identify sources of and student coping mechanisms for perceived stress and fatigue and to identify the relationship between students' perceived stress and fatigue. METHODS: A survey comprised of the Perceived Stress Scale, the Undergraduate Sources of Stress Survey, and the Piper Fatigue Scale was administered to chiropractic students in their 2nd, 5th, and 8th trimesters of doctoral study. Data were analyzed by descriptive statistics, 1-way analysis of variance, and linear correlation tests. RESULTS: Students reported having moderate to high levels of stress and fatigue, with higher levels of stress and fatigue seen in women than in men. A nonsignificant difference among stress scores and a significant difference among fatigue scores were observed based on program term. Levels of stress predicted levels of fatigue, and stress was strongly correlated with psychological health, relationships with family members, mood, and need for learning accommodations. Fatigue was strongly correlated with psychological health, academic demands, and conflicts between studies and other activities. CONCLUSION: There are differences in the reporting of perceived stress and fatigue levels in this chiropractic student population based on gender. The correlation between fatigue and stress also suggests that measures that may alleviate one may likely affect the other. PMID- 27552031 TI - Spontaneous flexor tendon rupture due to an insufficiency fracture of the hamate hook in a patient with systemic lupus erythematosus: A case report. AB - INTRODUCTION: Spontaneous flexor tendon rupture is usually caused by trauma, systemic diseases, or carpal bone and joint disorders. Here we report a case of spontaneous flexor tendon rupture occurring in a systemic lupus erythematosus (SLE) patient following nonunion of the hamate hook after an insufficiency fracture, and which was also associated with tendon degeneration caused by SLE. CASE PRESENTATION: A 57-year-old woman was diagnosed with SLE 22 years ago and being treated with oral prednisolone. She became unable to flex her left little finger without any history of trauma or sporting activity. CT showed nonunion of the hamate hook. MRI showed rupture of the flexor digitorum profundus tendon of the little finger. We performed tendon transfer and excision of the hamate hook. She recovered active flexion of the little finger at 4 months postoperatively with full satisfaction. DISCUSSION: There was no history of trauma that could have caused nonunion of the hamate hook. We considered that the insufficiency fracture of the hamate hook occurred as a result of osteoporosis caused by SLE and long-term steroid use. Nonunion of the hamate hook caused mechanical attrition of the tendons, and in combination with the tendon degeneration caused by SLE, further resulted in rupture of the flexor tendon. CONCLUSION: When we encounter a case of spontaneous flexor tendon rupture in a patient with systemic disease such as SLE or long-term steroid use, attention should be paid to the state of the carpal bones and joints as they sometimes accompany unexpected causes. PMID- 27552032 TI - Late reconstruction of the patellar tendon in rheumatoid arthritis using bone patellar tendon-bone allograft. AB - INTRODUCTION: chronic patellar tendon rupture is rare and its incidence and prevalence are unknown. Furthermore, the data about late reconstruction of the patellar tendon in rheumatoid arthritis is limited. Such condition, if not managed properly, can substantially affect the patient's activities of daily living. CASE PRESENTATION: We report a case of chronic patellar tendon rupture in a 49 years old lady who has been suffering from rheumatoid arthritis for over 20 years. She presented with an inability to extend the right knee which started suddenly a year and a half ago without any history of trauma. She underwent reconstruction of the patellar tendon using a massive BTB allograft. Three years after surgery, the patient had an active range of motion between -20 and 120 degrees and was walking normally without any external support. DISCUSSION: When the primary repair of the patellar tendon is not possible, it is necessary to either repair with autologous augmentation or use a graft to reconstruct the tendon. We believe autografts may not be suitable in the presence of rheumatoid arthritis since the disease is associated with excessive levels of collagenase that could contribute to the degeneration of the tendons. CONCLUSION: Late patellar tendon reconstruction in rheumatoid arthritis is a challenging procedure, and we believe it is best performed using an allograft to achieve the desired outcome. PMID- 27552033 TI - Esthesioneuroblastoma located in the thoracic extradural space: Case report. AB - OBJECTIVE: Esthesioneuroblastoma accounted for only 6% of the malignant nasal cavity neoplasms (ENB) is a rare tumor which originates from the olfactory epithelium. ENB's are locally agresive and can metastasize by lymphatic and hematogenous routes. A patient with the mass on the nasal dorsum was reported in this article. CASE HISTORY: A 52-year-old-man admitted to the hospital with a 3 months history of progressive nasal obstruction, epistaxis and mass on the nasal dorsum. On rhinoscopy, a polypoid mass was seen in the both nasal cavity and intranasal biopsy with local anesthesia was performed. Histopathologic diagnosis of the tumor was Kadish stage B esthesioneuroblastoma. Tumor was excised by using bilateral endoscopic endonasal resection and lateral rhinotomy approach and paranasal radiotherapy performed postoperatively. Ten months after surgery, neck metastasis was occured and patient was underwent neck dissection. Twenteeth months after initial treatment, distant metastasis was identified on the T 10 vertebra and following the cranial and spinal radiotherapy to the neck he was free of local recurrence at follow up 13 months after surgery. CONCLUSION: It has been known that the metastasis of the ENB to the spinal cord is an uncommon event, and it occurs often years after initial diagnosis. MRI scan is helpful for making the diagnosis, and surgery is the treatment of choice for obtaining diagnostic tissue and debulking the tumor. Radiotherapy is also a mainstay of postoperative treatment. PMID- 27552034 TI - Primary hydatid cyst of pancreas: Case report and review of literature. AB - INTRODUCTION: Hydatid disease is caused by the larval stage of Echinococcus granulosus. It most commonly affects the liver and lung. Pancreatic hydatid cyst (PHC) is very rare with incidence of 0.14%-2%. PRESENTATION OF CASE: A 40year old lady presented with epigastric pain for last 3 months. A 5*5cm abdominal lump occupying the epigastric and left hypochondrial region was noted on physical examination. Ultrasonography (USG) and Contrast enhanced Computed Tomogrpahy (CT) revealed a 55*57mm cystic structure in the pancreatic body. Endoscopic ultrasound guided fluid aspiration cytology revealed normal Carcinoembryonic antigen and Amylase levels. Cytological examination was noncontributory. During open surgical exploration, it was found to be a hydatid cyst. After irrigation with scolicidal agent and evacuation of cystic contents, Partial cystectomy with external drainage was done. Histopathological biopsy revealed Hydatid cyst. Post-operative ELISA (Enzyme linked immunosorbent assay) for Echinococcal antigen was positive. DISCUSSION: PHC is a rare entity. Most common mode of spread is hematogenous. Cysts in pancreatic head can present as obstructive jaundice. Cysts in body and tail are usually asymptomatic. USG, CT and Hydaitd serology can help in diagnosis and monitoring recurrence. Surgical exploration is treatment of choice. Options include pericystectomy, partial cystectomy+/- external drainage/omentopexy, marsupialization or cysto-enterostomy. Preoperative and Post-operative anti helminthic (Albendazole) is recommended. CONCLUSION: PHC can masquerade as pseudocyst or cystic neoplasm of pancreas. It should always be considered in the differential diagnosis of cystic pancreatic lesion in patients from endemic regions. PMID- 27552035 TI - Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis. AB - Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. PMID- 27552036 TI - Integrated multi-biomarker responses in two dreissenid species following metal and thermal cross-stress. AB - With current global changes, the combination of several stressors such as temperature and contaminants may impact species distribution and ecosystem functioning. In this study, we evaluated the combined impact of two metals (Ni and Cr) with a thermal stress (from 12 to 17 degrees C) on biomarker responses in two bivalves, Dreissena rostriformis bugensis and Dreissena polymorpha. Biomarkers are informative tools to evaluate exposure and effects of stressors on organisms. The set of 14 biomarkers measured here was representative of both physiologic (filtration activity) and cellular antioxidant and detoxification mechanisms. Our aim was to study the response pattern of both species, and its meaning in terms of invasive potential. The implications for the use of these mussels in environmental monitoring are also discussed. Results evidenced that the two species do not respond to multiple stressors in the same way. Indeed, the effects of contamination on biomarker responses were more marked for D. polymorpha, especially under nickel exposure. While we cannot conclude as to the effect of temperature, invasiveness could be influenced by species sensitivity to contaminants. The physiological and cellular differences between D. polymorpha and D. r. bugensis might also be of concern for environmental risk assessment. The two species present differential bioaccumulation patterns, filtration activity and cellular biomarker responses. If D. polymorpha populations decline, their substitution by D. r. bugensis for biomonitoring or laboratory studies will not be possible without a deeper understanding of biomarker responses of the new invasive. PMID- 27552037 TI - Multigenerational effects of tris(1,3-dichloro-2-propyl) phosphate on the free living ciliate protozoa Tetrahymena thermophila exposed to environmentally relevant concentrations and after subsequent recovery. AB - Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is considered a re-emerging environmental pollutant, and exposure to environmentally relevant concentrations has been shown to cause individual developmental toxicity in zebrafish and the water flea (Daphnia magna). However, multigenerational effects during exposure to TDCIPP and after subsequent recovery were unknown. In the present study, individuals of a model aquatic organism, the ciliated protozoan, T. thermophila were exposed to environmentally-relevant concentrations of TDCIPP (0, 300 or 3000 ng/L) for 60 days (e.g., theoretically 372 generations) followed by a 60-day period of recovery, during which T. thermophila were not exposed to TDCIPP. During exposure and after exposure, effects at the molecular, histological, individual and population levels were examined. Multigenerational exposure to 300 or 3000 ng TDCIPP/L for 60 days significantly decreased numbers of individuals, sizes of individuals, expressed as length and width of bodies, number of cilia, and depth and diameter of basal bodies of cilia, and up-regulated expressions of genes related to assembly and maintenance of cilia. Complete or partial recoveries of theoretical sizes of populations as well as sizes of individuals and expressions of genes were observed during the 60-day recovery period. Effects on number of cilia and depth and diameter of basal body of cilia were not reversible and could still be observed long after cease of TDCIPP exposure. Collectedly, and shown for the first time, multigenerational effects to T. thermophila were caused by exposure to environmentally relevant concentrations of TDCIPP. Also, there were multi-generational effects at the population level that were not caused by carry-over exposure to TDCIPP. The "permanent" alterations and their potential significance are discussed. PMID- 27552038 TI - No enhancement of cyanobacterial bloom biomass decomposition by sediment microbial fuel cell (SMFC) at different temperatures. AB - The sediment microbial fuel cell (SMFC) has potential application to control the degradation of decayed cyanobacterial bloom biomass (CBB) in sediment in eutrophic lakes. In this study, temperatures from 4 to 35 degrees C were investigated herein as the major impact on SMFC performance in CBB-amended sediment. Under low temperature conditions, the SMFC could still operate, and produced a maximum power density of 4.09 mW m-2 at 4 degrees C. Coupled with the high substrate utilization, high output voltage was generated in SMFCs at high temperatures. The application of SMFC affected the anaerobic fermentation progress and was detrimental to the growth of methanogens. At the same time, organic matter of sediments in SMFC became more humified. As a result, the fermentation of CBB was not accelerated with the SMFC application, and the removal efficiency of the total organic matter was inhibited by 5% compared to the control. Thus, SMFC could operate well year round in sediments with a temperature ranging from 4 to 35 degrees C, and also exhibit practical value by inhibiting quick CBB decomposition in sediments in summer against the pollution of algae organic matter. PMID- 27552039 TI - Experimental and in silico assessment of fate and effects of the antipsychotic drug quetiapine and its bio- and phototransformation products in aquatic environments. AB - The antipsychotic drug quetiapine (QUT) has been frequently detected in sewage treatment plants. However, information on the fate of QUT in aquatic environments and its behavior during UV treatment is limited. In this study, QUT is shown not to be readily biodegradable in the Closed Bottle Test and the Manometric Respirometry Test according to OECD guidelines. The main biotransformation product (BTP) formed in the tests, a carboxylic acid derivative, was identified by means of high-resolution mass spectrometry. This BTP is presumably a human metabolite and showed higher detection rates than QUT in a river sampling campaign conducted in northern Germany. UV elimination kinetics of QUT at different initial concentrations (226.5, 45.3, 11.3, and 2.3 MUmol L-1) were faster at lower initial concentrations. All seven phototransformation products (PTPs) could be still identified at initial concentration of 11.3 MUmol L-1. The photolytic mixture generated after 128 min of photolysis of QUT was not better biodegradable than QUT. Initial UV treatment of QUT led to the formation of several additional BTPs. Four of them were identified. The bacterial cytotoxicity and genotoxicity before and after phototransformation of QUT in a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829) showed cytotoxic effects in the LBT for QUT. Furthermore, PTPs had similar cytotoxic effects on luminescent bacteria. The umu-test did not reveal any genotoxic activity for QUT or PTPs. In conclusion, the release of QUT into sewage treatment plants and aquatic environments could result in the formation of a main BTP. Additional UV treatment of QUT would lead to the formation of additional BTPs. Moreover, treatment did not result in lower toxicity to tested organisms. In conclusion, UV treatment of QUT should be considered critically as a potential treatment for QUT in aquatic systems. PMID- 27552040 TI - Nano-TiO2 affects Cu speciation, extracellular enzyme activity, and bacterial communities in sediments. AB - In aquatic ecosystems, titanium dioxide nanoparticles (nano-TiO2) coexist with heavy metals and influence the existing forms and toxicities of the metal in water. However, limited information is available regarding the ecological risk of this coexistence in sediments. In this study, the effect of nano-TiO2 on Cu speciation in sediments was investigated using sequential extraction. The microcosm approach was also employed to analyze the effects of the coexistence of nano-TiO2 and Cu on extracellular enzyme activity and bacterial communities in sediments. Results showed that nano-TiO2 decreased the organic matter-bound fraction of Cu and increased the corresponding residual fraction Cu. As a result, speciation of exogenous Cu in sediments changed. During the course of the 30-day experiment, the presence of nano-TiO2 did not affect Cu-induced changes in bacterial community structure. However, the coexistence of nano-TiO2 and Cu restrained the activity of bacterial extracellular enzymes, such as alkaline phosphatase and beta-glucosidase. The degree of inhibition also varied because of the different properties of extracellular enzymes. This research highlighted the importance of understanding and predicting the effects of the coexistence of nanomaterials and other pollutants in sediments. PMID- 27552042 TI - In situ passive sampling of sediments in the Lower Duwamish Waterway Superfund site: Replicability, comparison with ex situ measurements, and use of data. AB - Superfund sites with sediments contaminated by hydrophobic organic compounds (HOCs) can be difficult to characterize because of the complex nature of sorption to sediments. Porewater concentrations, which are often used to model transport of HOCs from the sediment bed into overlying water, benthic organisms, and the larger food web, are traditionally estimated using sediment concentrations and sorption coefficients estimated using equilibrium partitioning (EqP) theory. However, researchers have begun using polymeric samplers to determine porewater concentrations since this method does not require knowledge of the sediment's sorption properties. In this work, polyethylene passive samplers were deployed into sediments in the field (in situ passive sampling) and mixed with sediments in the laboratory (ex situ active sampling) that were contaminated with polychlorinated biphenyls (PCBs). The results show that porewater concentrations based on in situ and ex situ sampling generally agreed within a factor of two, but in situ concentrations were consistently lower than ex situ porewater concentrations. Imprecision arising from in situ passive sampling procedures does not explain this bias suggesting that field processes like bioirrigation may cause the differences observed between in situ and ex situ polymeric samplers. PMID- 27552041 TI - PM2.5 pollution is substantially affected by ammonia emissions in China. AB - Urban air quality in China has been declining substantially in recent years due to severe haze episodes. The reduction of sulfur dioxide (SO2) and nitrogen oxide (NOx) emissions since 2013 does not yet appear to yield substantial benefits for haze mitigation. As the reductions of those key precursors to secondary aerosol formation appears not to sufficient, other crucial factors need to be considered for the design of effective air pollution control strategies. Here we argue that ammonia (NH3) plays a - so far - underestimated role in the formation of secondary inorganic aerosols, a main component of urban fine particulate matter (PM2.5) concentrations in China. By analyzing in situ concentration data observed in major cities alongside gridded emission data obtained from remote sensing and inventories, we find that emissions of NH3 have a more robust association with the spatiotemporal variation of PM2.5 levels than emissions of SO2 and NOx. As a consequence, we argue that urban PM2.5 pollution in China in many locations is substantially affected by NH3 emissions. We highlight that more efforts should be directed to the reduction of NH3 emissions that help mitigate PM2.5 pollution more efficiently than other PM2.5 precursors. Such efforts will yield substantial co-benefits by improving nitrogen use efficiency in farming systems. As a consequence, such integrated strategies would not only improve urban air quality, but also contribute to China's food-security goals, prevent further biodiversity loss, reduce greenhouse gas emissions and lead to economic savings. PMID- 27552043 TI - Sourcing methane and carbon dioxide emissions from a small city: Influence of natural gas leakage and combustion. AB - Natural gas leakage and combustion are major sources of methane (CH4) and carbon dioxide (CO2), respectively; however, our understanding of emissions from cities is limited. We mapped distribution pipeline leakage using a mobile CH4 detection system, and continuously monitored atmospheric CO2 and CH4 concentrations and carbon isotopes (delta13C-CO2 and delta13C-CH4) for one-year above Ithaca, New York. Pipeline leakage rates were low (<0.39 leaks mile-1), likely due to the small extent of cast iron and bare steel within the distribution pipeline system (2.6%). Our atmospheric monitoring demonstrated that the isotopic composition of locally emitted CO2 approached the delta13C range of natural gas combustion in winter, correlating to natural gas power generation patterns at Cornell's Combined Heat and Power Plant located 600 m southeast of the monitoring site. Atmospheric CH4 plumes were primarily of natural gas origin, were observed intermittently throughout the year, and were most frequent in winter and spring. No correlations between the timing of atmospheric natural gas CH4 plumes and Cornell Plant gas use patterns could be drawn. However, elevated CH4 and CO2 concentrations were observed coincident with high winds from the southeast, and the plant is the only major emission source in that wind sector. Our results demonstrate pipeline leakage rates are low in cities with a low extent of leak prone pipe, and natural gas power facilities may be an important source of urban and suburban emissions. PMID- 27552044 TI - Arsenic sorption to nanoparticulate mackinawite (FeS): An examination of phosphate competition. AB - Nanoparticulate mackinawite (FeS) can be an important host-phase for arsenic (As) in sulfidic, subsurface environments. Although not previously investigated, phosphate (PO43-) may compete with As for available sorption sites on FeS, thereby enhancing As mobility in FeS-bearing soils, sediments and groundwater systems. In this study, we examine the effect of PO43- on sorption of arsenate (As(V)) and arsenite (As(III)) to nanoparticulate FeS at pH 6, 7 and 9. Results show that PO43- (at 0.01-1.0 mM P) did not significantly affect sorption of either As(V) or As(III) to nanoparticulate FeS at initial aqueous As concentrations ranging from 0.01 to 1.0 mM. At pH 9 and 7, sorption of both As(III) and As(V) to nanoparticulate FeS was similar, with distribution coefficient (Kd) values spanning 0.76-15 L g-1 (which corresponds to removal of 87-98% of initial aqueous As(III) and As(V) concentrations). Conversely, at pH 6, the sorption of As(III) was characterized by substantially higher Kd values (6.3 93.4 L g-1) than those for As(V) (Kd = 0.21-0.96 L g-1). Arsenic K-edge X-ray absorption near edge structure (XANES) spectroscopy indicated that up to 52% of the added As(V) was reduced to As(III) in As(V) sorption experiments, as well as the formation of minor amounts of an As2S3-like species. In As(III) sorption experiments, XANES spectroscopy also demonstrated the formation of an As2S3-like species and the partial oxidation of As(III) to As(V) (despite the strictly O2 free experimental conditions). Overall, the XANES data indicate that As sorption to nanoparticulate FeS involves several redox transformations and various sorbed species, which display a complex dependency on pH and As loading but that are not influenced by the co-occurrence of PO43-. This study shows that nanoparticulate FeS can help to immobilize As(III) and As(V) in sulfidic subsurface environments where As co-exists with PO43-. PMID- 27552045 TI - Characterization and source apportionment of PM2.5-bound polycyclic aromatic hydrocarbons from Shanghai city, China. AB - Polycyclic aromatic hydrocarbons (PAHs) were studied in 230 daily fine particulate matter (PM2.5) samples collected in four seasons at urban and suburban sites of Shanghai, China. This study focused on the emission sources of PAHs and its dynamic results under different weather conditions and pollution levels and also emphasized on the spatial sources of PM2.5 and PAHs at a regional level. Annual concentrations of PM2.5 and 16 EPA priority PAHs were 53 MUg/m3 and 6.9 ng/m3, respectively, with highest levels in winter. Positive matrix factorization (PMF) modeling identified four sources of PAHs: coal combustion, traffic, volatilization and biomass combustion, and coking, with contributions of 34.9%, 27.5%, 21.1% and 16.5%, respectively. The contribution of traffic, a local indicative source, increased from 17.4% to 28.7% when wind speed changed from >2m/s to <2m/s, and increased from 18.3% to 31.3% when daily PAH concentrations changed from below to above the annual mean values. This indicated that local sources may have larger contributions under stagnant weather when poorer dispersion conditions and lower wind speed led to the accumulation of local emitted pollutants. The trajectory clustering and potential source contribution function (PSCF) and concentration weighted trajectory (CWT) models showed clearly that air parcels moved from west had highest concentrations of PM2.5, total PAHs and high molecular weight (HMW) PAHs. While small differences were found among all five clusters in low molecular weight (LMW) PAHs. Sector analyses determined that regional transport source contributed 39.8% to annual PM2.5 and 52.5% to PAHs, mainly from western regions and varying with seasons. This work may make contribution to a better understanding and control of the increasingly severe air pollution in China as well as other developing Asian countries. PMID- 27552046 TI - Active biomonitoring for assessing effects of metal polluted sediment resuspension on gammarid amphipods during fluvial traffic. AB - The resuspension of polluted sediments by boat traffic could release substantial amounts of metals to the water column, affecting at the same time their bioavailability. In order to characterize the impact of sediment resuspensions on biota, caged amphipods have been deployed on three different channelized watercourses in Northern France. Firstly, the biological responses of transplanted freshwater gammarid amphipods, Gammarus fossarum, described by trace metal accumulation, feeding and reproduction activities were quite similar for the three water courses despite the differences of metal contamination and navigability. Secondly, the concentrations of metals accumulated in gammarids never exceeded the contamination thresholds previously defined for Co, Cu, Cr and Zn. Values were in the same order of magnitude whatever the studied site despite: (i) large differences noticed in the sediment quality and (ii) some concentrations in the overlying waters exceeding the Environmental Quality Standards (EQS) defined by the Water Framework Directive. Conversely, Pb was highly bioaccumulated with values systematically exceeding the threshold value whatever the site. Therefore, the impact of navigation cannot be proved and the difference between the 3 monitoring periods is rather attributed to environmental variability, probably linked to the seasonality. Moreover, this study also confirms that organisms sampled from a local population in the vicinity of the three studied watercourses could be used as test organisms, leading to similar results than the ones obtained with reference gammarids initially used for developing all the biological responses. This would simplify and then promote the development of studies based on gammarid amphipod, G. fossarum, as bioindicators. PMID- 27552047 TI - Effects of disturbance and vegetation type on total and methylmercury in boreal peatland and forest soils. AB - Mercury (Hg) concentrations in freshwater fish relates to aquatic Hg concentrations, which largely derives from soil stores of accumulated atmospheric deposition. Hg in catchment soils as a source for aquatic Hg is poorly studied. Here we test if i) peatland soils produce more methylmercury (MeHg) than forest soils; ii) total Hg (THg) concentrations in top soils are determined by atmospheric inputs, while MeHg is produced in the soils; and iii) soil disturbance promotes MeHg production. In two small boreal catchments, previously used in a paired-catchment forest harvest manipulation study, forest soils and peatlands were sampled and analysed for Hg species and additional soil chemistry. In the undisturbed reference catchment, soils were sampled in different vegetation types, of varying productivity as reflected in tree density, where historical data on precipitation and throughfall Hg and MeHg fluxes were available. Upper soil THg contents were significantly correlated to throughfall inputs of Hg, i.e. lowest in the tree-less peatland and highest in the dense spruce forest. For MeHg, top layer concentrations were similar in forest soils and peatlands, likely related to atmospheric input and local production, respectively. The local peatland MeHg production was documented through significantly higher MeHg-to-THg ratios in the deeper soil layer samples. In the disturbed catchment, soils were sampled in and just outside wheeltracks in an area impacted by forest machinery. Here, MeHg concentrations and the MeHg-to-THg ratios in the upper 5 cm were weakly significantly (p = 0.07) and significantly (p = 0.04) different in and outside of the wheeltracks, respectively, suggesting that soil disturbance promotes methylation. Differences in catchment Hg and MeHg streamwater concentrations were not explained by soil Hg and MeHg information, perhaps because hydrological pathways are a stronger determinant of streamwater chemistry than small variations in soil chemistry driven by disturbance and atmospheric inputs of Hg. PMID- 27552048 TI - Is mercury from small-scale gold mining prevalent in the southeastern Peruvian Amazon? AB - There is an ongoing debate on the fate of mercury (Hg) in areas affected by artisanal and small-scale gold mining (ASGM). Over the last 30 years, ASGM has released 69 tons of Hg into the southeastern Peruvian Amazon. To investigate the role of suspended matter and hydrological factors on the fate of ASGM-Hg, we analysed riverbank sediments and suspended matter along the partially ASGM affected Malinowski-Tambopata river system and examined Hg accumulation in fish. In addition, local impacts of atmospheric Hg emissions on aquatic systems were assessed by analysing a sediment core from an oxbow lake. Hg concentrations in riverbank sediments are lower (20-53 ng g-1) than in suspended matter (~400-4000 ng g-1) due to differences in particle size. Elevated Hg concentrations in suspended matter from ASGM-affected river sections (~1400 vs. ~30-120 ng L-1 in unaffected sections) are mainly driven by the increased amount of suspended matter rather than increased Hg concentrations in the suspended matter. The oxbow lake sediment record shows low Hg concentrations (64-86 ng g-1) without evidence of any ASGM-related increase in atmospheric Hg input. Hg flux variations are mostly an effect of variations in sediment accumulation rates. Moreover, only 5% of the analysed fish (only piscivores) exceed WHO recommendations for human consumption (500 ng g-1). Our findings show that ASGM-affected river sections in the Malinowski-Tambopata system do not exhibit increased Hg accumulation, indicating that the released Hg is either retained at the spill site or transported to areas farther away from the ASGM areas. We suspect that the fate of ASGM-Hg in such tropical rivers is mainly linked to transport associated with the suspended matter, especially during high water situations. We assume that our findings are typical for ASGM-affected areas in tropical regions and could explain why aquatic systems in such ASGM regions often show comparatively modest enrichment in Hg levels. PMID- 27552049 TI - Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys. AB - The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders. PMID- 27552050 TI - Patched1 and Patched2 inhibit Smoothened non-cell autonomously. AB - Smoothened (Smo) inhibition by Patched (Ptch) is central to Hedgehog (Hh) signaling. Ptch, a proton driven antiporter, is required for Smo inhibition via an unknown mechanism. Hh ligand binding to Ptch reverses this inhibition and activated Smo initiates the Hh response. To determine whether Ptch inhibits Smo strictly in the same cell or also mediates non-cell-autonomous Smo inhibition, we generated genetically mosaic neuralized embryoid bodies (nEBs) from mouse embryonic stem cells (mESCs). These experiments utilized novel mESC lines in which Ptch1, Ptch2, Smo, Shh and 7dhcr were inactivated via gene editing in multiple combinations, allowing us to measure non-cell autonomous interactions between cells with differing Ptch1/2 status. In several independent assays, the Hh response was repressed by Ptch1/2 in nearby cells. When 7dhcr was targeted, cells displayed elevated non-cell autonomous inhibition. These findings support a model in which Ptch1/2 mediate secretion of a Smo-inhibitory cholesterol precursor. PMID- 27552051 TI - bMERB domains are bivalent Rab8 family effectors evolved by gene duplication. AB - In their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study, we have thoroughly characterized a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication. This study is the first to thoroughly characterize a Rab effector protein that contains two separate Rab binding sites within a single domain, allowing Micals and EHBPs to bind two Rabs simultaneously, thus suggesting previously unknown functions of these effector molecules in endosomal trafficking. PMID- 27552052 TI - Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network. AB - Motor neurons of the crustacean cardiac ganglion generate virtually identical, synchronized output despite the fact that each neuron uses distinct conductance magnitudes. As a result of this variability, manipulations that target ionic conductances have distinct effects on neurons within the same ganglion, disrupting synchronized motor neuron output that is necessary for proper cardiac function. We hypothesized that robustness in network output is accomplished via plasticity that counters such destabilizing influences. By blocking high threshold K(+) conductances in motor neurons within the ongoing cardiac network, we discovered that compensation both resynchronized the network and helped restore excitability. Using model findings to guide experimentation, we determined that compensatory increases of both GA and electrical coupling restored function in the network. This is one of the first direct demonstrations of the physiological regulation of coupling conductance in a compensatory context, and of synergistic plasticity across cell- and network-level mechanisms in the restoration of output. PMID- 27552053 TI - Revealing the neural fingerprints of a missing hand. AB - The hand area of the primary somatosensory cortex contains detailed finger topography, thought to be shaped and maintained by daily life experience. Here we utilise phantom sensations and ultra high-field neuroimaging to uncover preserved, though latent, representation of amputees' missing hand. We show that representation of the missing hand's individual fingers persists in the primary somatosensory cortex even decades after arm amputation. By demonstrating stable topography despite amputation, our finding questions the extent to which continued sensory input is necessary to maintain organisation in sensory cortex, thereby reopening the question what happens to a cortical territory once its main input is lost. The discovery of persistent digit topography of amputees' missing hand could be exploited for the development of intuitive and fine-grained control of neuroprosthetics, requiring neural signals of individual digits. PMID- 27552054 TI - Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage. AB - The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co transcriptional RNA-DNA products, which in some instances have been linked to DNA damage. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility. PMID- 27552055 TI - A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins. AB - Overproduced yeast ribosomal protein (RP) Rpl26 fails to assemble into ribosomes and is degraded in the nucleus/nucleolus by a ubiquitin-proteasome system quality control pathway comprising the E2 enzymes Ubc4/Ubc5 and the ubiquitin ligase Tom1. tom1 cells show reduced ubiquitination of multiple RPs, exceptional accumulation of detergent-insoluble proteins including multiple RPs, and hypersensitivity to imbalances in production of RPs and rRNA, indicative of a profound perturbation to proteostasis. Tom1 directly ubiquitinates unassembled RPs primarily via residues that are concealed in mature ribosomes. Together, these data point to an important role for Tom1 in normal physiology and prompt us to refer to this pathway as ERISQ, for excess ribosomal protein quality control. A similar pathway, mediated by the Tom1 homolog Huwe1, restricts accumulation of overexpressed hRpl26 in human cells. We propose that ERISQ is a key element of the quality control machinery that sustains protein homeostasis and cellular fitness in eukaryotes. PMID- 27552056 TI - Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex. AB - Cortical responses to sensory stimuli are modulated by behavioral state. In the primary visual cortex (V1), visual responses of pyramidal neurons increase during locomotion. This response gain was suggested to be mediated through inhibitory neurons, resulting in the disinhibition of pyramidal neurons. Using in vivo two photon calcium imaging in layers 2/3 and 4 in mouse V1, we reveal that locomotion increases the activity of vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV)-positive interneurons during visual stimulation, challenging the disinhibition model. In darkness, while most VIP and PV neurons remained locomotion responsive, SST and excitatory neurons were largely non-responsive. Context-dependent locomotion responses were found in each cell type, with the highest proportion among SST neurons. These findings establish that modulation of neuronal activity by locomotion is context-dependent and contest the generality of a disinhibitory circuit for gain control of sensory responses by behavioral state. PMID- 27552057 TI - Mapping transiently formed and sparsely populated conformations on a complex energy landscape. AB - Determining the structures, kinetics, thermodynamics and mechanisms that underlie conformational exchange processes in proteins remains extremely difficult. Only in favourable cases is it possible to provide atomic-level descriptions of sparsely populated and transiently formed alternative conformations. Here we benchmark the ability of enhanced-sampling molecular dynamics simulations to determine the free energy landscape of the L99A cavity mutant of T4 lysozyme. We find that the simulations capture key properties previously measured by NMR relaxation dispersion methods including the structure of a minor conformation, the kinetics and thermodynamics of conformational exchange, and the effect of mutations. We discover a new tunnel that involves the transient exposure towards the solvent of an internal cavity, and show it to be relevant for ligand escape. Together, our results provide a comprehensive view of the structural landscape of a protein, and point forward to studies of conformational exchange in systems that are less characterized experimentally. PMID- 27552058 TI - Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. AB - BACKGROUND: Vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with an increased risk of developing chronic lung disease. OBJECTIVES: To evaluate supplementation with vitamin A on the incidence of death or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birth weight (VLBW) infants compared with a control (placebo or no supplementation), and to consider the effect of the supplementation route, dose, and timing. SEARCH METHODS: For the original review and subsequent updates, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Science Citation Index, and the Oxford Database of Perinatal Trials. The reference lists of relevant trials, paediatric and nutrition journals, and conference abstracts and proceedings were handsearched up to 2010.For the 2016 update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1 May 2016), EMBASE (1 May 2016), and CINAHL (1 May 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials comparing vitamin A supplementation with a control (placebo or no supplementation) or other dosage regimens in VLBW infants (birth weight <= 1500 grams or less than 32 weeks' gestation). DATA COLLECTION AND ANALYSIS: Two review authors screened the search results, extracted data, and assessed the trials for risk of bias. Results were reported as risk ratios (RR), risk differences (RD), and number needed to treat to benefit (NNTB), all with 95% confidence intervals (CI). Trialists were contacted for additional data. MAIN RESULTS: Eleven trials met the inclusion criteria. Ten trials (1460 infants) compared vitamin A supplementation with a control and one (120 infants) compared different regimens of vitamin A supplementation. Compared to the control group, vitamin A appeared to have a small benefit in reducing the risk of death or oxygen requirement at one month of age (typical RR 0.93, 95% CI 0.88 to 0.99; typical RD -0.05, 95% CI -0.10 to -0.01; NNTB 20, 95% CI 10 to 100; 6 studies, 1165 infants) and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (typical RR 0.87, 95% CI 0.77 to 0.99; typical RD -0.07, 95% CI -0.13 to -0.01; NNTB 11, 95% CI 6 to 100; 5 studies, 986 infants) (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (typical RR 0.92, 95% CI 0.84 to 1.01; typical RD -0.05, 95% CI -0.11 to 0.01; 4 studies, 1089 infants). Neurodevelopmental assessment of 88% of the surviving infants in the largest trial showed no difference between the groups at 18 to 22 months of age, corrected for prematurity (low-quality evidence). There is no evidence to support different vitamin A dosing regimens. No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful. AUTHORS' CONCLUSIONS: Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention. PMID- 27552059 TI - Control of information in working memory: Encoding and removal of distractors in the complex-span paradigm. AB - The article reports four experiments with complex-span tasks in which encoding of memory items alternates with processing of distractors. The experiments test two assumptions of a computational model of complex span, SOB-CS: (1) distractor processing impairs memory because distractors are encoded into working memory, thereby interfering with memoranda; and (2) free time following distractors is used to remove them from working memory by unbinding their representations from list context. Experiment 1 shows that distractors are erroneously chosen for recall more often than not-presented stimuli, demonstrating that distractors are encoded into memory. Distractor intrusions declined with longer free time, as predicted by distractor removal. Experiment 2 shows these effects even when distractors precede the memory list, ruling out an account based on selective rehearsal of memoranda during free time. Experiments 3 and 4 test the notion that distractors decay over time. Both experiments show that, contrary to the notion of distractor decay, the chance of a distractor intruding at test does not decline with increasing time since encoding of that distractor. Experiment 4 provides additional evidence against the prediction from distractor decay that distractor intrusions decline over an unfilled retention interval. Taken together, the results support SOB-CS and rule out alternative explanations. Data and simulation code are available on Open Science Framework: osf.io/3ewh7. PMID- 27552060 TI - Effects of long-term administration of pantoprazole on bone mineral density in young male rats. AB - BACKGROUND: Epidemiological studies suggest that long-term administration of proton pump inhibitors (PPIs) may decrease bone mineral density (BMD) and increase the risk of osteoporotic fractures. The aim of the study was to assess the influence of pantoprazole on bone metabolism in growing rats. METHODS: The experiment was carried out on twenty-four young male Wistar rats divided into two groups receiving either pantoprazole at the dose of 3mg/kg or vehicle for 12 weeks. Femoral bone mineral density (BMD) and bone histomorphometry were assessed. Serum total calcium, inorganic phosphate and markers of bone turnover were measured. RESULTS: In pantoprazole-treated rats a decreased BMD was detected (0.2618+/-0.0133g/cm(2)vs. 0.2715+/-0.0073g/cm(2), p<0.05). Bone histomorphometry revealed a decrease in growth plate thickness (G.Pl.RTh.) (161.0+/-27.8MUm vs. 195.0+/-20.8, p<0.05) in pantoprazole-treated animals. Serum total calcium level and osteocalcin concentrations were decreased in the pantoprazole-treated group (9.62+/-0.55mg/dl vs. 10.15+/-0.38mg/dl, p<0.05 and 242.7+/-44.4pg/ml vs. 342.5+/ 123.3pg/ml, p<0.05, respectively). CONCLUSION: We observed that PPIs might have a negative impact on bone formation in growing rats mainly due to their inhibitory effects on the gastric proton pump, with probable deterioration of calcium absorption and decrease in growth plate thickness. PMID- 27552061 TI - Resveratrol intake enhances indoleamine-2,3-dioxygenase activity in humans. AB - BACKGROUND: Resveratrol is a polyphenol compound found in various nutrients that was shown to have immunomodulatory, anti-cancerogenic, and cardioprotective effects. The regulation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme in inflammatory tryptophan metabolism, has been proposed to be involved in resveratrol's biological effects. These observations, however, rely on in vitro findings and animal studies. Therefore, we assessed the impact of resveratrol on tryptophan metabolism after oral intake in humans. METHODS: Healthy volunteers were orally administrated 5g resveratrol (n=8) or placebo (n=2) in a pilot study. IDO activity was determined by analyzing plasma levels of tryptophan and kynurenine. Determination of the immune activation marker neopterin was included in the analysis. RESULTS: Resveratrol administration significantly reduced tryptophan levels 2.5h (p<0.001) and 5h (p<0.001) after treatment. Kynurenine levels were slightly, but not significantly, elevated 2.5h after the intervention, which resulted in an 1.33- and 1.30-fold increase of the kynurenine to tryptophan ratio at 2.5h (p<0.01) and 5h (p<0.01), respectively. Neopterin levels were not affected by resveratrol administration. CONCLUSION: This is the first evidence of a modulatory effect of orally administered resveratrol on tryptophan metabolism in humans. Since IDO has been shown to play a crucial role in immunity, cancer development and regulation of vascular tone, the modulation of this enzyme might be involved in resveratrol's diverse biological effects. PMID- 27552062 TI - Intravenous lidocaine infusions in a multidirectional model of treatment of neuropathic pain patients. AB - BACKGROUND: Neuropathic pain, is caused by damage or disease affecting the somatosensory nervous system, leads to deterioration of the quality of life of patients. Most commonly, this deterioration is due to the inefficacy of treatment or to the adverse effects of systemic treatment. Pharmacotherapy of neuropathic pain involves the use of antiepileptic agents, antidepressants, and opioids that may lead to numerous adverse effects, particularly in elderly patients. Intravenous infusions of lidocaine may improve the efficacy of the analgesic treatment of neuropathic pain patients while not causing any significant adverse effects. METHODS: In our study, we carried out a retrospective analysis of 85 patients with various neuropathic pain syndromes. In this group, 81 patients received 3-25 intravenous infusions of lidocaine (5mg/kg of body weight over 30min). In the remaining 4 patients, the treatment was discontinued after the first infusion due to the lack of efficacy. RESULTS: The analgesic effect of intravenous lidocaine was better when the intensity of pain experienced before the infusion was high. In addition, better effects were observed in elderly patients. No need to interrupt the infusion occurred in any of the patients. No serious adverse effects were observed either. Transient dizziness, not requiring additional treatment, occurred in 5 patients after the infusion. CONCLUSIONS: The best therapeutic effects of lidocaine infusion was observed in pain symptoms characterized by the highest intensity of baseline pain. Intravenous lidocaine administered at the dose of 5mg/kg of body weight over 30min is effective, safe and caused no significant adverse effects. PMID- 27552063 TI - Combining hypobaric hypoxia or hyperbaric oxygen postconditioning with memantine reduces neuroprotection in 7-day-old rat hypoxia-ischemia. AB - BACKGROUND: Perinatal hypoxia-ischemia causes brain injury in neonates, but a fully successful treatment to prevent changes in the brain has yet to be developed. The aim of this study was to evaluate the effect of combining memantine treatment with HBO (2.5 ATA) or HH (0.47 ATA) on neonatal hypoxia ischemia brain injury. METHODS: 7-day old rats were subjected to hypoxia-ischemia (H-I) and treated with combination of memantine and HBO or HH. The brain damage was evaluated by examination of infarct area and the number of apoptotic cells in CA1 region of hippocampus. Additionally, the level of reactive oxygen species (ROS) was measured. RESULTS: Memantine, HBO or HH postconditioning applied at short time (1-6h) after H-I, and repeated for two subsequent days, resulted in significant neuroprotection. The reduction in ipsilateral hemisphere weight deficit and in the size of infarct area was observed 14days after H-I. A reduction in apoptosis and ROS level was also observed. Combining memantine with HBO or HH resulted in a loss of neuroprotection. CONCLUSIONS: Our results show that, combining HBO or HH postconditioning with memantine produce no additive increase in the neuroprotective effect. On the contrary, combining the treatments resulted in lower neuroprotection in comparison to the effects of memantine, HBO or HH alone. PMID- 27552064 TI - Influence of a Propagating Megahertz Surface Acoustic Wave on the Pattern Deposition of Solute Mass off an Evaporating Solution. AB - We study the influence of a megahertz Rayleigh surface acoustic wave (SAW), propagating in a solid substrate, on the pattern deposition of a solute mass off an evaporating solution. An experimental procedure, where a film of a solution undergoes a controlled evaporation in a chamber, shows that the SAW alters the state of the pattern deposition. Increasing the power of the SAW supports an increase in the density of the deposited patterns. Beyond threshold conditions, the deposited patterns merge and we observe the deposition of a solid film. A simplified theory suggests that the SAW deforms the geometry of the film, which is predominantly governed by the capillary stress. The deformation of the film taking place alongside with the evaporation of the solution increases the concentration near the pinned three phase contact line at the front of the film, which is closer to the source of the SAW, on the expense of the concentration at the rear. The increased concentration translates to the deposition of solute mass over an increased area near the front of the film, which explains the experimental observation. PMID- 27552065 TI - A Qualitative Study on the Practice of Yoga for Women with Pain-Associated Endometriosis. AB - OBJECTIVES: To understand the meaning women with pain-associated endometriosis attribute to yoga practice regarding their physical and emotional state at the beginning of the practice; pain management by integrating body and mind; secondary benefits of the practice of yoga, such as self-knowledge, self-care, and autonomy; and the role of the yoga group as psychosocial support. DESIGN: Qualitative study conducted simultaneously with a randomized clinical trial. SETTING: Public university hospital in southeastern Brazil between August 2013 and December 2014. PARTICIPANTS: Fifteen women with pain-associated endometriosis who practiced yoga for 8 weeks. INTERVENTION: After completing the twice-a-week program, all women participated in a single, semi-structured interview. Interviews were recorded and transcribed verbatim, and thematic analyses were performed. OUTCOME MEASURES: The main themes of analysis were women's expectations regarding the practice of yoga, physical and emotional state of women at the beginning of yoga practice, control and pain management through the integration of body and mind, secondary benefits, acquisition of self-knowledge and autonomy, and the role of yoga group as psychosocial support. RESULTS: All participants reported that yoga was beneficial to control pelvic pain. They related that they were aware of the integration of body and psyche during yoga practice and that this helped in the management of pain. Women said they had identified a relationship between pain management and breathing techniques (pranayama) learned in yoga and that breathing increased their ability to be introspective, which relieved pain. The participants have developed greater self knowledge, autonomy, and self-care and have reduced the use of pain and psychiatric medications. They created ties among themselves, suggesting that the yoga group allowed psychosocial support. CONCLUSIONS: Bodily and psychosocial mechanisms to control pain were identified in women with endometriosis. To reach such control, it is crucial that mind and body integrative techniques are learned. PMID- 27552066 TI - Expression of RANKL by peripheral neutrophils and its association with bone mineral density in COPD. AB - BACKGROUND AND OBJECTIVE: Osteoporosis is a major co-morbidity of COPD, but the mechanistic links between diseases of the lung and the bone remain elusive. Human neutrophils express the osteoclast activation factor RANKL (receptor activator of NF-kB ligand) and act directly on osteoclasts to promote bone loss. Given that neutrophils are key effector cells in the pathogenesis of COPD, these same cells, by expressing RANKL, may be involved in osteoporosis of COPD. METHODS: We enrolled 59 male patients with COPD, 32 smokers with normal lung function and 25 healthy non-smokers of the same gender as controls. The expression of RANKL on peripheral neutrophils was detected by flow cytometry. The plasma concentrations of pro-inflammatory cytokines were measured by ELISA. We analysed the association of RANKL + neutrophils with bone mineral density (BMD), lung function and the levels of cytokines. RESULTS: RANKL + neutrophils in the blood of COPD patients were increased as compared to smokers and healthy controls, and the percentage of RANKL + neutrophils was higher in patients with low BMD as compared to those with normal BMD. The percentage of RANKL + neutrophils showed negative correlations with BMD and forced expiratory volume in 1 s (FEV1) % predicted. Further analysis showed that activated neutrophils were increased and expressed a higher level of RANKL in COPD patients. Plasma levels of IL-1beta, IL-6 and IL-8 were increased in COPD patients and correlated with RANKL expression by neutrophils. CONCLUSION: Our results show that RANKL-expressing neutrophils are increased in male patients with COPD and associated with BMD and lung function, suggesting that these cells may play a role in osteoclastogenesis in COPD. PMID- 27552067 TI - Holt-Oram syndrome because of the novel TBX5 mutation c.481A>C. PMID- 27552068 TI - Developing brain networks of attention. AB - PURPOSE OF REVIEW: Attention is a primary cognitive function critical for perception, language, and memory. We provide an update on brain networks related to attention, their development, training, and pathologies. RECENT FINDINGS: An executive attention network, also called the cingulo-opercular network, allows voluntary control of behavior in accordance with goals. Individual differences among children in self-regulation have been measured by a higher order factor called effortful control, which is related to the executive network and to the size of the anterior cingulate cortex. SUMMARY: Brain networks of attention arise in infancy and are related to individual differences, including pathology during childhood. Methods of training attention may improve performance and ameliorate pathology. PMID- 27552070 TI - Radiogenomics: towards a personalized radiation oncology. AB - PURPOSE OF REVIEW: This article evaluates the field of radiogenomics within recent developments in genomics and radiation biology. RECENT FINDINGS: Many pediatric cancer survivors have undergone treatment with radiation, putting them at risk for long-term side-effects associated with this therapy, especially cardiac disease and secondary malignancies. Advancements in our understanding of radiation biology have led to the understanding that genetics plays a major role in determining a patient's susceptibility to developing long-term side-effects, leading to the field of 'radiogenomics'. Although initial candidate gene studies did not demonstrate replicable genetic variants that affected radiosensitivity, genome-wide association studies have recently begun to identify genes that may help explain some of the observed variation in radiosensitivity. As genomic sciences continues to progress and whole genome studies become more accessible, our understanding of the genes responsible for radiosensitivity will continue to progress. SUMMARY: The field of radiogenomics continues to evolve with the availability and improved cost of genomic technologies allowing the study of an increasing fraction of the human genome. Studies into genetic factors influencing individual radiosensitivity will increase our understanding of radiobiology and improve our ability to counsel patients on the adverse effects they will likely experience. PMID- 27552069 TI - Navigating genetic diagnostics in patients with hearing loss. AB - PURPOSE OF REVIEW: In the age of targeted genomic enrichment and massively parallel sequencing, there is no more efficient genetic testing method for the diagnosis of hereditary hearing loss. More clinical tests are on the market, which can make choosing good tests difficult. RECENT FINDINGS: More and larger comprehensive genetic studies in patients with hearing loss have been published recently. They remind us of the importance of looking for both single nucleotide variation and copy number variation in all genes implicated in nonsyndromic hearing loss. They also inform us of how a patient's history and phenotype provide essential information in the interpretation of genetic data. SUMMARY: Choosing the most comprehensive genetic test improves the chances of a genetic diagnosis and thereby impacts clinical care. PMID- 27552071 TI - Newborn screening: a review of history, recent advancements, and future perspectives in the era of next generation sequencing. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize the development and recent advancements of newborn screening. RECENT FINDINGS: Early initiation of medical care has modified the outcome for many disorders that were previously associated with high morbidity (such as cystic fibrosis, primary immune deficiencies, and inborn errors of metabolism) or with significant neurodevelopmental disabilities (such as phenylketonuria and congenital hypothyroidism). The new era of mass spectrometry and next generation sequencing enables the expansion of the newborn screen panel, and will help to address technical issues such as turnaround time, and decreasing false-positive and false negative rates for the testing. SUMMARY: The newborn screening program is a successful public health initiative that facilitates early diagnosis of treatable disorders to reduce long-term morbidity and mortality. PMID- 27552072 TI - Perspectives on the impact of storage duration on blood quality and transfusion outcomes. AB - BACKGROUND & OBJECTIVES: Red blood cells (RBCs) may be stored up to 42 days before transfusion, per US and EU standards. Although there is ample evidence that RBCs undergo deleterious changes during storage, studies assessing outcomes relative to storage time report conflicting findings. This study investigated RBC storage duration perspectives and practices among blood banking and transfusion professionals. MATERIALS & METHODS: A survey was administered at the American Association of Blood Banking annual meeting in October 2014 (N = 69). RESULTS: On average, participants believed RBC storage should not exceed 34 days (median: 35; range: 1-52), and estimated that RBCs are typically stored 21 days before transfusion at their institutions (median: 20; range: 10-40). There was 97% agreement that minimizing/reversing changes during RBC storage may produce clinical benefits; however, 80% believed the research does not consistently demonstrate worse outcomes using older blood. Two-thirds agreed that RBC storage duration is a major concern, but 81% agreed most institutions are not pursuing measures to shorten storage. CONCLUSIONS: This study found that many transfusion professionals believe RBCs should be stored for fewer than the 42 days currently allowed and that further efforts are warranted to abrogate changes in stored RBCs. These findings suggest a need for increased awareness of potential consequences of extended RBC storage and for strategies to maximize transfusion benefits. PMID- 27552073 TI - Association of good glycemic control and cost of diabetes care: Experience from a tertiary care hospital in Bangladesh. AB - AIM: The present study was undertaken to assess the cost-effectiveness of good glycemic control in a population of Bangladeshi people with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted among 496 registered patients with >1year duration of diabetes. Glycated hemoglobin A1c level <7% was judged as the cut-off value for good glycemic control. All treatment-related records from the last year were collected from patients' guide books and all cost components were calculated. RESULTS: Among patients, 31% had good glycemic control. The average annual cost was US$ 314 per patient. Patients with poor glycemic control were significantly more likely to have complications [(p=0.049) OR 1.5] and comorbidities [(p=0.02) OR 1.5]. The annual cost increased rapidly with complications/comorbidities. In multivariable logistic regression analysis, gender (p=0.003) and cost of care (p=0.006) were significantly associated with glycemic control, and the presence of any comorbidities/complications was associated with 1.8-fold higher odds of poor glycemic control (p=0.013 95% CI: 1.131-2.786). CONCLUSION: Good glycemic control can lead to substantial cost saving through prevention and control of complications. PMID- 27552074 TI - Hardware design of the cortical-diencephalic centre of the lower urinary tract neuroregulator system. AB - The neuroregulator system in humans controls organ and system functioning. This system comprises a set of neural centres that are distributed along the spinal cord and act independently together with their nerve interconnections. The centres involved in this task were isolated in previous studies through investigations of the functioning and composition of the neuroregulator system of the lower urinary tract to elucidate their individual performances and enable the creation of a general neuroregulator system model capable of operating at the neuronal level. Although the long-term goal of our research is the development of a system on chip (SoC) capable of behaving as a fully programmable neuroregulator system, this work is another step in which we test the viability of the hardware design of one of these neuroregulator centres (specifically the cortical diencephalic centre) to achieve a first prototype and architectural proposal. To this end, the behaviour of this centre has been isolated, a hardware design implemented on FPGA has been proposed to create a prototype, a simulation environment has been built for the evaluation, and finally, the results have been analysed. This system verified that the functional behaviour corresponded to the expected behaviour in humans and that the operational requirements for the implementation were technically and architecturally viable. PMID- 27552076 TI - Nanoflow-Nanospray Mass Spectrometry Metabolomics Reveals Disruption of the Urinary Metabolite Profiles of HIV-Positive Patients on Combination Antiretroviral Therapy. AB - BACKGROUND: The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic, and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention. METHODS: HIV-positive patients were recruited from an HIV clinic and divided into cART-naive and cART-exposed groups. HIV-negative patients were recruited from a sexual health clinic. All 89 subjects were white males. Targeted biochemistry analyses were performed on plasma samples. Urine samples were collected after an overnight fast and analyzed with a highly sensitive untargeted metabolomic method using nanoflow/nanospray liquid chromatography-time-of-flight mass spectrometry. Data sets were analyzed using projection modeling to detect metabolite markers of cART exposure. RESULTS: Metabolites or parent compounds of all cART drugs were detected in urine extracts of all but one of the cART-exposed patients confirming adherence to the pharmaceutical regimen. Analysis of urine samples from patients on cART revealed significant reductions in selected bile acids, lipid, nucleoside, and androgen metabolites. However, plasma concentrations of free or conjugated testosterone remained unchanged indicating possible disruption of androgen transport or excretion in urine of patients on cART. CONCLUSIONS: Discovery-based metabolomics reveals the potential to identify novel markers of cART intervention and metabolite disruption in HIV-positive patients, which may enable investigation of the efficacy, compliance, and side effects of these pharmaceutical mixtures to be investigated. PMID- 27552077 TI - Vitamin D: a 'wanted' supernatural power or a power of wishful thinking. PMID- 27552078 TI - Black N/H-TiO2 Nanoplates with a Flower-Like Hierarchical Architecture for Photocatalytic Hydrogen Evolution. AB - A facile two-step strategy was used to prepare black of hydrogenated/nitrogen doped TiO2 nanoplates (NHTA) with a flower-like hierarchical architecture. In situ nitriding and self-assembly was realized by hydrothermal synthesis using tripolycyanamide as a N source and as a structure-directing agent. After thorough characterization, it was found that the hydrogenation treatment did not damage the flower-like architecture but distorted the anatase crystal structure and significantly changed the band structure of NHTA owing to the increased concentration of oxygen vacancies, hydroxyl groups, and Ti3+ cations. Under AM 1.5 illumination, the photocatalytic H2 evolution rate on the black NHTA was approximately 1500 MUmol g-1 h-1 , which was much better than the N-doped TiO2 nanoplates (~690 MUmol g-1 h-1 ). This improvement in the hydrogen evolution rate was attributed to a reduced bandgap, enhanced separation of the photogenerated charge carriers, and an increase in the surface-active sites. PMID- 27552079 TI - Liquid-liquid phase separation in cellular signaling systems. AB - Liquid-liquid demixing or phase separation of protein with RNA is now recognized to be a key part of the mechanism for assembly of ribonucleoprotein granules. Cellular signaling also appears to employ phase separation as a mechanism for amplification or control of signal transduction both within the cytoplasm and at the membrane. The concept of receptor clustering, identified more than 3 decades ago, is now being examined through the lens of phase separation leading to new insights. Intrinsically disordered proteins or regions are central to these processes owing to their flexibility and accessibility for dynamic protein protein interactions and post-translational modifications. We review some recent examples, examine the mechanisms driving phase separation and delineate the implications for signal transduction systems. PMID- 27552080 TI - Conformational insight into multi-protein signaling assemblies by hydrogen deuterium exchange mass spectrometry. AB - Hydrogen-deuterium exchange (HDX) mass spectrometry (MS) can provide information about proteins that can be challenging to obtain by other means. Structure/function relationships, binding interactions, and the effects of modification have all been measured with HDX MS for a diverse and growing array of signaling proteins and multiprotein signaling complexes. As a result of hardware and software improvements, receptors and complexes involved in cellular signaling-including those associated with membranes-can now be studied. The growing body of HDX MS studies of signaling complexes at membranes is particularly exciting. Recent examples are presented to illustrate what can be learned about signaling proteins with this technique. PMID- 27552082 TI - First Report of Kidney Lesions Due to Renicola sp. (Digenea: Trematoda) in Free Living Magellanic Penguins ( Spheniscus magellanicus Forster, 1781) Found on the Coast of Brazil. AB - This paper presents the first report of parasites from the genus Renicola sp. in the kidneys of Magellanic penguins. The histological analysis revealed inflammatory infiltrate (eonsinophils, lymphocytes, and plasmocytes), together with fibroplasia and compression of the adjacent ducts. PMID- 27552081 TI - Resolution advances in cryo-EM enable application to drug discovery. AB - The prospect that the structures of protein assemblies, small and large, can be determined using cryo-electron microscopy (cryo-EM) is beginning to transform the landscape of structural biology and cell biology. Great progress is being made in determining 3D structures of biological assemblies ranging from icosahedral viruses and helical arrays to small membrane proteins and protein complexes. Here, we review recent advances in this field, focusing especially on the emerging use of cryo-EM in mapping the binding of drugs and inhibitors to protein targets, an application that requires structure determination at the highest possible resolutions. We discuss methods used to evaluate the information contained in cryo-EM density maps and consider strengths and weaknesses of approaches currently used to measure map resolution. PMID- 27552083 TI - Enemies and brothers in arms: Candida albicans and gram-positive bacteria. AB - Candida albicans is an important human opportunistic fungal pathogen which is frequently found as part of the normal human microbiota. It is well accepted that the fungus interacts with other components of the resident microbiota and that this impacts the commensal or pathogenic outcome of C. albicans colonization. Different types of interactions, including synergism or antagonism, contribute to a complex balance between the multitude of different species. Mixed biofilms of C. albicans and streptococci are a well-studied example of a mutualistic interaction often potentiating the virulence of the individual members. In contrast, other bacteria like lactobacilli are known to antagonize C. albicans, and research has just started elucidating the mechanisms behind these interactions. This scenario is even more complicated by a third player, the host. This review focuses on interactions between C. albicans and gram-positive bacteria whose investigation will without doubt ultimately help understanding C. albicans infections. PMID- 27552085 TI - Congenital Microphthalmia, Anophthalmia and Coloboma among Live Births in Denmark. AB - PURPOSE: This study aims to quantify the occurrence of the congenital eye malformations anophthalmia (AO), microphthalmia (MO) and coloboma among liveborn infants in Denmark, and to estimate the rate of chromosomal abnormalities in this group of patients. METHODS: A cohort of patients born in 1995-2012 with diagnoses of MO/AO or coloboma was identified from the Danish National Patient Registry (DNPR), and their ocular and extra-ocular diagnoses were reviewed. In order to assess the occurrence of chromosomal abnormalities in the cohort, the data were cross-referenced with the Danish Cytogenetic Central Registry (DCCR). RESULTS: We identified 415 patients with MO/AO/coloboma in the DNPR. The total number of live births from 1995-2012 was 1,174,299, and the average birth prevalence of MO/AO/coloboma was 3.6/10,000 live births and of MO/AO was 1.2/10,000 live births. Extra-ocular abnormalities were observed in 32.1% of MO/AO cases and 21.7% of coloboma cases. Chromosome analysis was performed in 36.1% of the cohort, and 14.7% of cases had an abnormal karyotype. In 8.7% of the cohort, a chromosome microarray analysis was performed, and in 44.4% of cases, a possibly pathogenic copy number variation was observed. CONCLUSION: The birth prevalence of MO/AO/coloboma in Denmark has been steady at 3.6/10,000 live births during the last 17 years. The rate of syndromic cases was lower compared to other studies. A relatively high rate of pathogenic chromosomal aberrations was observed, suggesting an important role for cytogenetic analysis in this group of patients. PMID- 27552086 TI - Normal and Anomalous Diffusion: An Analytical Study Based on Quantum Collision Dynamics and Boltzmann Transport Theory. AB - Diffusion, an emergent nonequilibrium transport phenomenon, is a nontrivial manifestation of the correlation between the microscopic dynamics of individual molecules and their statistical behavior observed in experiments. We present a thorough investigation of this viewpoint using the mathematical tools of quantum scattering, within the framework of Boltzmann transport theory. In particular, we ask: (a) How and when does a normal diffusive transport become anomalous? (b) What physical attribute of the system is conceptually useful to faithfully rationalize large variations in the coefficient of normal diffusion, observed particularly within the dynamical environment of biological cells? To characterize the diffusive transport, we introduce, analogous to continuous phase transitions, the curvature of the mean square displacement as an order parameter and use the notion of quantum scattering length, which measures the effective interactions between the diffusing molecules and the surrounding, to define a tuning variable, eta. We show that the curvature signature conveniently differentiates the normal diffusion regime from the superdiffusion and subdiffusion regimes and the critical point, eta = etac, unambiguously determines the coefficient of normal diffusion. To solve the Boltzmann equation analytically, we use a quantum mechanical expression for the scattering amplitude in the Boltzmann collision term and obtain a general expression for the effective linear collision operator, useful for a variety of transport studies. We also demonstrate that the scattering length is a useful dynamical characteristic to rationalize experimental observations on diffusive transport in complex systems. We assess the numerical accuracy of the present work with representative experimental results on diffusion processes in biological systems. Furthermore, we advance the idea of temperature-dependent effective voltage (of the order of 1 MUV or less in a biological environment, for example) as a dynamical cause of the perpetual molecular movement, which eventually manifests as an ordered motion, called the diffusion. PMID- 27552084 TI - Base Excision Repair of N6-Deoxyadenosine Adducts of 1,3-Butadiene. AB - The important industrial and environmental carcinogen 1,3-butadiene (BD) forms a range of adenine adducts in DNA, including N6-(2-hydroxy-3-buten-1-yl)-2' deoxyadenosine (N6-HB-dA), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2' deoxyadenosine (1,N6-HMHP-dA), and N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2' deoxyadenosine (N6,N6-DHB-dA). If not removed prior to DNA replication, these lesions can contribute to A -> T and A -> G mutations commonly observed following exposure to BD and its metabolites. In this study, base excision repair of BD induced 2'-deoxyadenosine (BD-dA) lesions was investigated. Synthetic DNA duplexes containing site-specific and stereospecific (S)-N6-HB-dA, (R,S)-1,N6 HMHP-dA, and (R,R)-N6,N6-DHB-dA adducts were prepared by a postoligomerization strategy. Incision assays with nuclear extracts from human fibrosarcoma (HT1080) cells have revealed that BD-dA adducts were recognized and cleaved by a BER mechanism, with the relative excision efficiency decreasing in the following order: (S)-N6-HB-dA > (R,R)-N6,N6-DHB-dA > (R,S)-1,N6-HMHP-dA. The extent of strand cleavage at the adduct site was decreased in the presence of BER inhibitor methoxyamine and by competitor duplexes containing known BER substrates. Similar strand cleavage assays conducted using several eukaryotic DNA glycosylases/lyases (AAG, Mutyh, hNEIL1, and hOGG1) have failed to observe correct incision products at the BD-dA lesion sites, suggesting that a different BER enzyme may be involved in the removal of BD-dA adducts in human cells. PMID- 27552087 TI - Host-Guest Self-Assembly Toward Reversible Thermoresponsive Switching for Bacteria Killing and Detachment. AB - A facile method to construct reversible thermoresponsive switching for bacteria killing and detachment was currently developed by host-guest self-assembly of beta-cyclodextrin (beta-CD) and adamantane (Ad). Ad-terminated poly(N isopropylacrylamide) (Ad-PNIPAM) and Ad-terminated poly[2 (methacryloyloxy)ethyl]trimethylammonium chloride (Ad-PMT) were synthesized via atom transfer radical polymerization, and then assembled onto the surface of beta CD grafted silicon wafer (SW-CD) by simply immersing SW-CD into a mixed solution of Ad-PNIPAM and Ad-PMT, thus forming a thermoresponsive surface (SW-PNIPAM/PMT). Atomic force microscopy (AFM), X-ray photoelectron spectrometry (XPS), and water contact angle (WCA) analysis were used to characterize the surface of SW PNIPAM/PMT. The thermoresponsive bacteria killing and detachment switch of the SW PNIPAM/PMT was investigated against Staphyloccocus aureus. The microbiological experiments confirmed the efficient bacteria killing and detachment switch across the lower critical solution temperature (LCST) of PNIPAM. Above the LCST, the Ad PNIPAM chains on the SW-PNIPAM/PMT surface were collapsed to expose Ad-PMT chains, and then the exposed Ad-PMT would kill the attached bacteria. While below the LCST, the previously collapsed Ad-PNIPAM chains became more hydrophilic and swelled to cover the Ad-PMT chains, leading to the detachment of bacterial debris. Besides, the proposed method to fabricate stimuli-responsive surfaces with reversible switches for bacteria killing and detachment is facile and efficient, which creates a new route to extend the application of such smart surfaces in the fields requiring long-term antimicrobial treatment. PMID- 27552088 TI - Metabolic profile and pharmacokinetics of polyphyllin I, an anticancer candidate, in rats by UPLC-QTOF-MS/MS and LC-TQ-MS/MS. AB - Polyphyllin I (PPI), a natural steroidal saponin originating from rihzome of Paris polyphylla, is a potential anticancer candidate. Previous pharmacokinetics study showed that the oral bioavailability of PPI was very low, which suggested that certain amount of PPI might be metabolized in vivo. However, to date, information regarding the final metabolic fates of PPI is very limited. In this study, metabolites of PPI and their pharmacokinetics in rats were investigated using UPLC-QTOF-MS/MS and LC-TQ-MS/MS. A total of seven putative metabolites, including six phase I and one phase II metabolites, were detected and identified with three exact structures by comparison with authentic standards for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. The pharmacokinetics of prosapogenin A, trillin and diosgenin, three deglycosylation metabolites of PPI with definite anticancer effects, were further studied, which suggested that the metabolites underwent a prolonged absorption and slower elimination after intragastric administration of PPI at the dose of 500 mg/kg. This study provides valuable and new information on the metabolic fate of PPI, which will be helpful in further understanding its mechanism of action. PMID- 27552089 TI - Chorioamnionitis at birth does not increase the risk of neurodevelopmental disability in premature infants with bronchopulmonary dysplasia. AB - AIM: To compare preterm infants with no bronchopulmonary dysplasia (BPD), BPD with chorioamnionitis (BPDC) and BPD with no chorioamnionitis (BPDNC) for the association with neurodevelopmental disability (NDD) at three years corrected age. METHODS: Demographic and outcome data of infants with birthweight (BW) <=1250 g born during two epochs (1995-2000 and 2002-2007 with an interim washout period of one year) were compared on the basis of whether they had BPD, chorioamnionitis or both. Any NDD was considered present if there was either mild severe cerebral palsy (CP), cognitive delay, visual or hearing impairment. Logistic regression modelling was performed. RESULTS: Infants (n = 1009) were included into three groups - no BPD (n = 442), BPDNC (n = 437) and BPDC (n = 130). The adjusted odds ratio (aOR) of any NDD at three years in infants with BPDC versus BPDNC was 1.37; 95% CI 0.85-2.20, and for CP the aOR was 1.66; 95% CI 0.76-3.62. Infants in the BPDC group were of lower BW, gestational age and had longer length of hospital stay, duration of mechanical ventilation, more blood transfusions and sepsis compared to BPDNC and no BPD groups (all p < 0.001). CONCLUSION: Chorioamnionitis was not associated with any increase in the odds of NDD in infants with BPD at three years corrected age. PMID- 27552092 TI - Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma. AB - Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma. PMID- 27552090 TI - Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda. AB - BACKGROUND: Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. METHODS AND FINDINGS: Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (>=85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. CONCLUSIONS: Integrated delivery of time limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year. PMID- 27552091 TI - Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life. AB - BACKGROUND: Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. METHODS: At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965-1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. RESULTS: In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500-3,999 g; >=4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all). CONCLUSIONS: In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower, birth weight in males may contribute to less favourable cardiovascular autonomic regulation and potentially to an elevated cardiovascular risk in later life. PMID- 27552094 TI - Misinterpretation Rates of High-Grade Squamous Intraepithelial Lesion in the College of American Pathologists Gynecologic PAP Education and PAP Proficiency Test Program. AB - Context .- Misinterpretation of high-grade squamous intraepithelial lesion (HSIL) is an important problem in daily practice and in the College of American Pathologists (CAP) PAP Proficiency Test (PAP-PT). Objective .- To investigate factors related to misinterpretation of HSIL through responses in a proficiency test versus an educational environment. Design .- We retrospectively evaluated 28 000 responses in the PAP Education Program (PAP-Edu) and 59 140 responses in PAP PT from 1147 field-validated HSIL slides from 2007 to 2014. The related factors, such as program types, preparation types, participant types, and program years, were evaluated. Results .- Overall, 4.0% (2379 of 59 140) of responses for HSIL slides from PAP-PT were misinterpreted as either low-grade squamous intraepithelial lesion (LSIL) or negative, significantly more than those from PAP Edu (3.2%; 898 of 28 000). However, the false-negative rate (misinterpreted as negative) was 0.9% (519 of 59 140) for PAP-PT, lower than that for PAP-Edu (1.0%; 266 of 28 000). The misinterpretation rates in PAP-PT trended down with time. Misinterpretation rates did not vary significantly by preparation methods. The misinterpretation rate for HSIL in the pathologists' responses was lower than that in cytotechnologists' in PAP-PT. More HSIL was misinterpreted as LSIL than as benign in both programs. Cytotechnologists interpreted HSIL as LSIL twice as much as pathologists. The most common false-negative misinterpretations were negative for intraepithelial lesion or malignancy and reparative change. Conclusions .- The higher LSIL misinterpretation rate by cytotechnologists may be related to the differences in reporting responsibilities and proficiency test grading criteria. The trend of gradually decreasing misinterpretation rates of a reference diagnosis of HSIL in the PAP-PT program may be related to higher test taking confidence and better preparation through educational programs. The fact that pathologists performed better than cytotechnologists in PAP-PT, but not in PAP-Edu, may reflect a heightened approach and attentiveness in the test-taking environment for pathologists. PMID- 27552093 TI - Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens. AB - CONTEXT: -The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material. OBJECTIVE: -To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non-small cell lung carcinoma using cytologic preparations. DESIGN: -Nine cytopathologists from different institutions submitted cases of non-small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times. RESULTS: -Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases * 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%). CONCLUSION: -Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience. PMID- 27552095 TI - Development of a Companion Diagnostic for Pembrolizumab in Non-Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1. AB - Context .- Programmed death ligand-1 (PD-L1) expression by tumors may enable them to avoid immunosurveillance. Objective .- To develop a PD-L1 immunohistochemical assay using the 22C3 anti-PD-L1 murine monoclonal antibody on the Dako platform as a possible companion diagnostic for pembrolizumab in patients with non-small cell lung cancer. Design .- Tumor samples from 146 patients with non-small cell lung cancer treated with pembrolizumab in KEYNOTE-001 and for whom response data were available were scored according to their staining intensity by a single pathologist using 4 methods: percentage of tumor cells staining at any intensity (PS1), moderate/strong intensity (PS2), strong intensity (PS3), and H-score (PS1 + PS2 + PS3). The cutoff score for predicting response to pembrolizumab was determined using receiver operating characteristic analysis. Progression-free and overall survival were assessed in patients with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (n = 146). Results .- The 4 scoring methods assessed performed similarly; PS1 with a 50% cutoff score is the simplest and easiest method to implement in practice. Response to pembrolizumab was observed in 19 of 44 patients (43%) with a PS1 score of 50% or higher and 8 of 102 patients (8%) with PS1 lower than 50% (odds ratio, 8.93). Median progression-free and overall survival was 4.0 months and not yet reached, respectively, for patients with a PS1 of 50% or higher, and 2.1 and 6.1 months, respectively, for those with PS1 lower than 50%. Conclusion .- The PD-L1 immunohistochemical assay shows the potential for enrichment of trial populations and as a companion diagnostic tool in non-small cell lung cancer. PMID- 27552096 TI - The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer. AB - Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and the hypermutator phenotype. Here we evaluated whether the APOBEC3B deletion polymorphism also associates with clinical outcome of breast cancer. Copy number analysis was performed by quantitative PCR (qPCR) in primary tumors of 1,756 Dutch breast cancer patients. The APOBEC3B deletion was found in 187 patients of whom 16 carried a two-copy deletion and 171 carried a one-copy deletion. The prognostic value of the APOBEC3B deletion for the natural course of the disease was evaluated among 1,076 lymph-node negative (LNN) patients who did not receive adjuvant systemic treatment. No association was found between APOBEC3B copy number values and the length of metastasis-free survival (MFS; hazard ratio (HR) = 1.00, 95% confidence interval (CI) = 0.90-1.11, P = 0.96). Subgroup analysis by ER status also did not reveal an association between APOBEC3B copy number values and the length of MFS. The predictive value of the APOBEC3B deletion was assessed among 329 ER-positive breast cancer patients who received tamoxifen as the first line therapy for recurrent disease and 226 breast cancer patients who received first-line chemotherapy for recurrent disease. No association between APOBEC3B copy number values and the overall response rate (ORR) to either tamoxifen (odds ratio (OR) = 0.88, 95% CI = 0.69-1.13, P = 0.31) or chemotherapy (OR = 0.97, 95% CI = 0.71-1.33, P = 0.87) was found. Thus, in contrast to APOBEC3B mRNA levels, the APOBEC3B deletion polymorphism has neither a prognostic nor a predictive value for breast cancer patients. Although a correlation exists between APOBEC3B copy number and mRNA expression, it is relatively weak. This suggests that other mechanisms exist that may affect and therefore determine the prognostic value of APOBEC3B mRNA levels. PMID- 27552097 TI - The Selector Gene apterous and Notch Are Required to Locally Increase Mechanical Cell Bond Tension at the Drosophila Dorsoventral Compartment Boundary. AB - The separation of cells with distinct fates and functions is important for tissue and organ formation during animal development. Regions of different fates within tissues are often separated from another along straight boundaries. These compartment boundaries play a crucial role in tissue patterning and growth by stably positioning organizers. In Drosophila, the wing imaginal disc is subdivided into a dorsal and a ventral compartment. Cells of the dorsal, but not ventral, compartment express the selector gene apterous. Apterous expression sets in motion a gene regulatory cascade that leads to the activation of Notch signaling in a few cell rows on either side of the dorsoventral compartment boundary. Both Notch and apterous mutant clones disturb the separation of dorsal and ventral cells. Maintenance of the straight shape of the dorsoventral boundary involves a local increase in mechanical tension at cell bonds along the boundary. The mechanisms by which cell bond tension is locally increased however remain unknown. Here we use a combination of laser ablation of cell bonds, quantitative image analysis, and genetic mutants to show that Notch and Apterous are required to increase cell bond tension along the dorsoventral compartment boundary. Moreover, clonal expression of the Apterous target gene capricious results in cell separation and increased cell bond tension at the clone borders. Finally, using a vertex model to simulate tissue growth, we find that an increase in cell bond tension at the borders of cell clones, but not throughout the cell clone, can lead to cell separation. We conclude that Apterous and Notch maintain the characteristic straight shape of the dorsoventral compartment boundary by locally increasing cell bond tension. PMID- 27552098 TI - p110alpha and p110beta isoforms of PI3K signaling: are they two sides of the same coin? AB - Class-1 phosphatidylinositol-3-kinases (PI3Ks) are activated by a variety of extracellular stimuli and have been implicated in a wide range of cellular processes. p110alpha and p110beta are the two most studied isoforms of the class 1A PI3K signaling pathway. Although these two isoforms are ubiquitously expressed and play multiple redundant roles, they also have distinct functions within the cell. More recently, p110alpha and p110beta isoforms have been shown to translocate into the nucleus and play a role in DNA replication and repair, and in cell cycle progression. In the following Review article, we discuss the overlapping and unique roles of p110alpha and p110beta isoforms with a particular focus on their structure, expression analysis, subcellular localization, and signaling contributions in various cell types and model organisms. PMID- 27552100 TI - Multiple dispersal vectors drive range expansion in an invasive marine species. AB - The establishment and subsequent spread of invasive species is widely recognized as one of the most threatening processes contributing to global biodiversity loss. This is especially true for marine and estuarine ecosystems, which have experienced significant increases in the number of invasive species with the increase in global maritime trade. Understanding the rate and mechanisms of range expansion is therefore of significant interest to ecologists and conservation managers alike. Using a combination of population genetic surveys, environmental DNA (eDNA) plankton sampling and hydrodynamic modelling, we examined the patterns of introduction of the predatory Northern Pacific seastar (Asterias amurensis) and pathways of secondary spread within southeast Australia. Genetic surveys across the invasive range reveal some genetic divergence between the two main invasive regions and no evidence of ongoing gene flow, a pattern that is consistent with the establishment of the second invasive region via a human mediated translocation event. In contrast, hydrodynamic modelling combined with eDNA plankton sampling demonstrated that the establishment of range expansion populations within a region is consistent with natural larval dispersal and recruitment. Our results suggest that both anthropogenic and natural dispersal vectors have played an important role in the range expansion of this species in Australia. The multiple modes of spread combined with high levels of fecundity and a long larval duration in A. amurensis suggests it is likely to continue its range expansion and significantly impact Australian marine ecosystems. PMID- 27552099 TI - Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice. AB - Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3-8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3-8. PMID- 27552101 TI - Detailed Dietary Assessment in Patients with Inoperable Tumors: Potential Deficits for Nutrition Care Plans. AB - Advanced cancer often results in reduced dietary intake; however, data on actual intake at the time of diagnosis are limited. In the present study, a detailed dietary intake assessment was performed in patients with metastatic lung and upper gastrointestinal cancer, before initiation of systemic therapy. Basic demographics and performance status (PS) were recorded. Nutritional status was evaluated through anthropometry, Mini Nutritional Assessment (MNA), and 3 nonconsecutive 24-hour dietary recalls. Of the 84 patients enrolled, 61.4% were protein, energy, or protein-energy undernourished, regardless of body mass index (BMI) or MNA category. No differences in energy, macronutrients, and micronutrients intakes across BMI categories were recorded. Very low consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), irrespective of energy intake, tumor site, BMI category, or PS was found. Suboptimal micronutrients intakes were recorded even in well-nourished and overweight/obese patients. Patients with adequate PS and better MNA score reported significantly higher intake of certain macro- and micronutrients (all P < 0.05). Most patients exhibited reduced dietary intake in terms of energy, macronutrient, and micronutrient. Very low EPA and DHA intake was recorded for the whole sample, whereas micronutrient suboptimal intakes were also prevalent in well-nourished or overweight patients. All the above should be taken into account during patients' nutritional care. PMID- 27552102 TI - Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B. AB - SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV) infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV) by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-alpha, IFN-beta and IFN stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway. PMID- 27552103 TI - Comparing Volume Loss in Neuroanatomical Regions of Emotion versus Regions of Cognition in Healthy Aging. AB - Many emotional functions are relatively preserved in aging despite declines in several cognitive domains and physical health. High levels of happiness exist even among centenarians. To address the hypothesis of whether preservation of emotional function in healthy aging may relate to different rates of age-related volume loss across brain structures, we performed two volumetric analyses on structural magnetic resonance neuroimaging of a group of healthy aging research participants using Freesurfer version 5.1. Volumes selected as supporting cognition included bilateral midfrontal and lateral frontal gyri, lateral parietal and temporal cortex, and medial temporal lobes. Volumes supporting emotion included bilateral amygdala, rostral anterior cingulate, insula, orbitofrontal cortex, and nucleus accumbens. A cross-sectional analysis was performed using structural MRI scans from 258 subjects. We found no difference in proportional change between groups. A longitudinal mixed effects model was used to compare regional changes over time in a subset of 84 subjects. Again, there was no difference in proportional change over time. While our results suggest that aging does not collectively target cognitive brain regions more than emotional regions, subgroup analysis suggests relative preservation of the anterior cingulate cortex, with greater volume loss in the nucleus accumbens. Implications of these relative rates of age-related volume loss in healthy aging are discussed and merit further research. PMID- 27552104 TI - Continental-Scale Patterns Reveal Potential for Warming-Induced Shifts in Cattle Diet. AB - In North America, it has been shown that cattle in warmer, drier grasslands have lower quality diets than those cattle grazing cooler, wetter grasslands, which suggests warming will increase nutritional stress and reduce weight gain. Yet, little is known about how the plant species that comprise cattle diets change across these gradients and whether these shifts in dietary quality coincide with shifts in dietary composition, i.e. the relative abundance of different plant species consumed by cattle. To quantify geographic patterns in dietary composition, we analyzed the dietary composition and dietary quality of unsupplemented cattle from 289 sites across the central US by sequence-based analyses of plant DNA isolated from cattle fecal samples. Overall, assuming that the percentage of reads for a species in a sample corresponds to the percentage of protein derived from the species, only 45% of the protein intake for cattle was derived from grasses. Within the Great Plains, northern cattle relied more on grasses than southern cattle, which derived a greater proportion of their protein from herbaceous and woody eudicots. Eastern cattle were also more likely to consume a unique assemblage of plant species than western cattle. High dietary protein was not strongly tied to consumption of any specific plant species, which suggests that efforts to promote individual plant species may not easily remedy protein deficiencies. A few plant species were consistently associated with lower quality diets. For example, the diets of cattle with high amounts of Elymus or Hesperostipa were more likely to have lower crude protein concentrations than diets with less of these grasses. Overall, our analyses suggest that climatic warming will increase the reliance of cattle on eudicots as protein concentrations of grasses decline. Monitoring cattle diet with this DNA-based sequencing approach can be an effective tool for quantifying cattle diet to better increase animal performance and guide mitigation strategies to changing climates. PMID- 27552106 TI - The LG/J murine strain exhibits near-normal tendon biomechanical properties following a full-length central patellar tendon defect. AB - PURPOSE OF THE STUDY: Identifying biological success criteria is needed to improve therapies, and one strategy for identifying them is to analyze the RNA transcriptome for successful and unsuccessful models of tendon healing. We have characterized the MRL/MpJ murine strain and found improved mechanical outcomes following a central patellar tendon (PT) injury. In this study, we evaluate the healing of the LG/J murine strain, which comprises 75% of the MRL/MpJ background, to determine if the LG/J also exhibits improved biomechanical properties following injury and to determine differentially expressed transcription factors across the C57BL/6, MRL/MpJ and the LG/J strains during the early stages of healing. MATERIALS AND METHODS: A full-length, central PT defect was created in 16-20 week old MRL/MpJ, LG/J, and C57BL/6 murine strains. Mechanical properties were assessed at 2, 5, and 8 weeks post surgery. Transcriptomic expression was assessed at 3, 7, and 14 days following injury using a novel clustering software program to evaluate differential expression of transcription factors. RESULTS: Average LG/J structural properties improved to 96.7% and 97.2% of native LG/J PT stiffness and ultimate load by 8 weeks post surgery, respectively. We found the LG/J responded by increasing expression of transcription factors implicated in the inflammatory response and collagen fibril organization. CONCLUSIONS: The LG/J strain returns to normal structural properties by 8 weeks, with steadily increasing properties at each time point. Future work will characterize the cell populations responding to injury and investigate the role of the differentially expressed transcription factors during healing. PMID- 27552105 TI - Identification of ABC Transporter Interaction of a Novel Cyanoquinoline Radiotracer and Implications for Tumour Imaging by Positron Emission Tomography. AB - BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed in many cancers including lung, ovarian, breast, head and neck and brain. Mutation of this receptor has been shown to play a crucial role in the response of non-small cell lung carcinoma (NSCLC) to EGFR-targeted therapies. It is envisaged that imaging of EGFR using positron emission tomography (PET) could aid in selection of patients for treatment with novel inhibitors. We recognised multi-drug resistant phenotype as a threat to development of successful imaging agents. In this report, we describe discovery of a novel cyanoquinoline radiotracer that lacks ABC transporter activity. METHODS: Cellular retention of the prototype cyanoquinoline [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7 ethoxyquinolin-6-yl}-4-({[1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl]methyl}amino) but-2-enamide ([18F]FED6) and [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3 cyano-7-ethoxyquinolin-6-yl}-4-[({1-[(2R,5S)-3-fluoro-4,5-dihydroxy-6 (hydroxymethyl)oxan-2-yl]-1H-1,2,3-triazol-4-yl}methyl)amino]but-2-enamide ([18F]FED20) were evaluated to establish potential for imaging specificity. The substrate specificity of a number of cyanoquinolines towards ABC transporters was investigated in cell lines proficient or deficient in ABCB1 or ABCG2. RESULTS: FED6 demonstrated substrate specificity for both ABCG2 and ABCB1, a property that was not observed for all cyanoquinolines tested, suggesting scope for designing novel probes. ABC transporter activity was confirmed by attenuating the activity of transporters with drug inhibitors or siRNA. We synthesized a more hydrophilic compound [18F]FED20 to overcome ABC transporter activity. FED20 lacked substrate specificity for both ABCB1 and ABCG2, and maintained a strong affinity for EGFR. Furthermore, FED20 showed higher inhibitory affinity for active mutant EGFR versus wild-type or resistant mutant EGFR; this property resulted in higher [18F]FED20 cellular retention in active mutant EGFR expressing NSCLC. CONCLUSION: [18F]FED20 binds EGFR but is devoid of ABC transporter activity, thus, has potential for EGFR imaging. PMID- 27552107 TI - Shape-Controlled Synthesis of High-Quality Cu7 S4 Nanocrystals for Efficient Light-Induced Water Evaporation. AB - Copper sulfides (Cu2-x S), are a novel kind of photothermal material exhibiting significant photothermal conversion efficiency, making them very attractive in various energy conversion related devices. Preparing high quality uniform Cu2-x S nanocrystals (NCs) is a top priority for further energy-and sustainability relevant nanodevices. Here, a shape-controlled high quality Cu7 S4 NCs synthesis strategy is reported using sulfur in 1-octadecene as precursor by varying the heating temperature, as well as its forming mechanism. The performance of the Cu7 S4 NCs is further explored for light-driven water evaporation without the need of heating the bulk liquid to the boiling point, and the results suggest that as synthesized highly monodisperse NCs perform higher evaporation rate than polydisperse NCs under the identical morphology. Furthermore, disk-like NCs exhibit higher water evaporation rate than spherical NCs. The water evaporation rate can be further enhanced by assembling the organic phase Cu7 S4 NCs into a dense film on the aqueous solution surface. The maximum photothermal conversion efficiency is as high as 77.1%. PMID- 27552109 TI - Paracrine Effects of Leydig Cell Nodular Hyperplasia, Two Case Reports: A Neglected Phenomenon. AB - Leydig cell nodular hyperplasia (LCNH) is a lesion that is less characterized than the familiar Leydig cell tumors. The paracrine effects of these lesions on adjacent gonadal stroma have not been widely documented. We present two cases of precocious puberty in pre-pubertal boys found to have a single LCNH with adjacent focal maturation of the seminiferous tubules. Blood tests showed elevated serum testosterone and dehydroepiandrosterone (DHEAS). Ultrasound revealed unilateral testicular enlargement with irregular echogenicity. Radical orchiectomy was performed. Histologically Leydig cell nodular proliferation without destruction of surrounding tubules was seen. Mature seminiferous tubules undergoing spermatogenesis were noted adjacent to the lesion, while away from the lesion seminiferous tubules were as expected in pre-pubescent boys. These cases emphasize the potential presence of both paracrine and endocrine effects in Leydig cell nodular hyperplasia. However, instances of the endocrine effects of hyperplastic Leydig cell lesions are more widely reported than the paracrine effects. PMID- 27552108 TI - Characterization and Functional Analysis of PEBP Family Genes in Upland Cotton (Gossypium hirsutum L.). AB - Upland cotton (Gossypium hirsutum L.) is a naturally occurring photoperiod sensitive perennial plant species. However, sensitivity to the day length was lost during domestication. The phosphatidylethanolamine-binding protein (PEBP) gene family, of which three subclades have been identified in angiosperms, functions to promote and suppress flowering in photoperiod pathway. Recent evidence indicates that PEBP family genes play an important role in generating mobile flowering signals. We isolated homologues of the PEBP gene family in upland cotton and examined their regulation and function. Nine PEBP-like genes were cloned and phylogenetic analysis indicated the genes belonged to four subclades (FT, MFT, TFL1 and PEBP). Cotton PEBP-like genes showed distinct expression patterns in relation to different cotton genotypes, photoperiod responsive and cultivar maturity. The GhFT gene expression of a semi-wild race of upland cotton were strongly induced under short day condition, whereas the GhPEBP2 gene expression was induced under long days. We also elucidated that GhFT but not GhPEBP2 interacted with FD-like bZIP transcription factor GhFD and promote flowering under both long- and short-day conditions. The present result indicated that GhPEBP-like genes may perform different functions. This work corroborates the involvement of PEBP-like genes in photoperiod response and regulation of flowering time in different cotton genotypes, and contributes to an improved understanding of the function of PEBP-like genes in cotton. PMID- 27552110 TI - Language Sampling for Preschoolers With Severe Speech Impairments. AB - Purpose: The purposes of this investigation were to determine if measures such as mean length of utterance (MLU) and percentage of comprehensible words can be derived reliably from language samples of children with severe speech impairments and if such measures correlate with tools that measure constructs assumed to be related. Method: Language samples of 15 preschoolers with severe speech impairments (but receptive language within normal limits) were transcribed independently by 2 transcribers. Nonparametric statistics were used to determine which measures, if any, could be transcribed reliably and to determine if correlations existed between language sample measures and standardized measures of speech, language, and cognition. Results: Reliable measures were extracted from the majority of the language samples, including MLU in words, mean number of syllables per utterance, and percentage of comprehensible words. Language sample comprehensibility measures were correlated with a single word comprehensibility task. Also, language sample MLUs and mean length of the participants' 3 longest sentences from the MacArthur-Bates Communicative Development Inventory (Fenson et al., 2006) were correlated. Conclusion: Language sampling, given certain modifications, may be used for some 3-to 5-year-old children with normal receptive language who have severe speech impairments to provide reliable expressive language and comprehensibility information. PMID- 27552111 TI - Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis. AB - INTRODUCTION: Despite recent advances in pharmacological management, multiple sclerosis (MS), an autoimmune disease of the central nervous system, remains a leading cause of disability. In relapsing-remitting (RR)MS, neurologists most commonly utilize immunomodulatory or immunosuppressive agents to benefit their patients. With the introduction of humanized monoclonal antibodies (mAbs) ablation of distinct immune populations has become possible. Depletion of B cells by anti-CD20 mAbs has repeatedly proven to be a very rapid and effective means to diminish disease activity in RRMS. AREAS COVERED: We discuss the biological rationale, development, and recent clinical study results of the second generation anti-CD20 mAb ocrelizumab. Expert commentary: The topline results of two phase-III randomized clinical trials demonstrate superiority of ocrelizumab over interferon beta in RRMS patients with regards to clinical and paraclinical outcome parameters. The short term adverse events profile appears favorable. However, long-term effects of repeated B cell depletion are currently unknown. PMID- 27552113 TI - List-mode image reconstruction for positron emission tomography using tetrahedral voxels. AB - Image space decomposition based on tetrahedral voxels are interesting candidates for use in emission tomography. Tetrahedral voxels provide many of the advantages of point clouds with irregular spacing, such as being intrinsically multi resolution, yet they also serve as a volumetric partition of the image space and so are comparable to more standard cubic voxels. Additionally, non-rigid displacement fields can be applied to the tetrahedral mesh in a straight-forward manner. So far studies incorporating tetrahedral decomposition of the image space have concentrated on pre-calculated, node-based, system matrix elements which reduces the flexibility of the tetrahedral approach and the capacity to accurately define regions of interest. Here, a list-mode on-the-fly calculation of the system matrix elements is described using a tetrahedral decomposition of the image space and volumetric elements-voxels. The algorithm is demonstrated in the context of awake animal PET which may require both rigid and non-rigid motion compensation, as well as quantification within small regions of the brain. This approach allows accurate, event based, motion compensation including non-rigid deformations. PMID- 27552112 TI - Kin recognition is a nutrient-dependent inducible phenomenon. AB - Recognition and response to prospective competitors are crucial variables that must be considered in resource distribution and utilization in plant communities. Associated behaviors are largely mediated through the exchange of low-molecular weight exudates. These cues can significantly alter the root system architecture (RSA) between neighboring plants and are routinely sensitive enough to distinguish between plants of the same or different accessions, a phenomenon known as kin recognition (KR). Such refined discrimination of identity, based on the composition and detection of patterns of exudate signals is remarkable and provides insight into the chemical ecology of plant-plant interactions. The discovery that KR occurs in Arabidopsis thaliana provides a model system to resolve many of the mechanistic questions associated with this process. We hypothesized that the low-molecular weight cues which direct changes to the RSA during KR was driven by nutrient availability. Here we present evidence in support of a nutrient-inducible model for KR. Our findings underscore how exudate production and detection are influenced by nutrient availability as well as how this information is integrated into 'decisions' about competition and root system architecture which may have broader impacts on community composition. PMID- 27552114 TI - Further characterisation of cytokines in macropod marsupials: IL-10 and IL 10Delta3. AB - Interleukin-10 is an immunomodulatory cytokine that has been implicated, along with IFN-gamma, in the disease sequelae of mycobacterial infection. In order to investigate the role of IL-10 in marsupial disease models we sequenced and characterised the IL10 gene in the tammar wallaby (Macropus eugenii) and rufous hare-wallaby (Lagorchestes hirsutus). An isoform IL-10Delta3, in which an in frame deletion of exon 3 occurs, was discovered in both macropod species. Analysis of wallaby and other reported marsupial IL-10 homologs suggests that while marsupial IL-10 is comparable to that of human IL-10, the predicted IL 10Delta3 protein may play a more complicated role in the modulation of IL-10 directed responses. Expression of the canonical gene and splicing variant was confirmed in both wallabies, and the rufous hare-wallaby showed differential expression across lymph node, spleen and liver, with isoform expression detected in the lymph node. This characterisation and expression of IL-10 in de novo tissues provides a basis for further study into the role of IL-10 in disease models in marsupials. PMID- 27552115 TI - The effect of hepatocyte growth factor on secretory functions in human eosinophils. AB - Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-beta and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-beta transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF beta contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation. PMID- 27552116 TI - Sixteen years of change in the global terrestrial human footprint and implications for biodiversity conservation. AB - Human pressures on the environment are changing spatially and temporally, with profound implications for the planet's biodiversity and human economies. Here we use recently available data on infrastructure, land cover and human access into natural areas to construct a globally standardized measure of the cumulative human footprint on the terrestrial environment at 1 km(2) resolution from 1993 to 2009. We note that while the human population has increased by 23% and the world economy has grown 153%, the human footprint has increased by just 9%. Still, 75% the planet's land surface is experiencing measurable human pressures. Moreover, pressures are perversely intense, widespread and rapidly intensifying in places with high biodiversity. Encouragingly, we discover decreases in environmental pressures in the wealthiest countries and those with strong control of corruption. Clearly the human footprint on Earth is changing, yet there are still opportunities for conservation gains. PMID- 27552117 TI - BRAZILIAN BOOTY RETINOPATHY: PURTSCHER-LIKE RETINOPATHY WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH PMMA INJECTION INTO BUTTOCKS. AB - PURPOSE: To report a case of Purtscher-like retinopathy with paracentral acute middle maculopathy preceded by febrile illness after filler injection into the buttock muscles bilaterally for cosmesis to achieve a "Brazilian booty." METHODS: Retrospective case report. RESULTS: A 35-year-old female presented with febrile illness and then decreased vision after repeat polymethyl methacrylate injections into her buttock muscles in Mexico. Examination was significant for retinal whitening, especially in the perifoveal areas, and intraretinal hemorrhages. Optical coherence tomography and fluorescein angiography imaging were consistent with small-vessel ischemic disease in the retina and choroid. Once systemic infection was ruled out, patient was treated with high-dose intravenous and then oral steroids. Vision recovery was good, with retinal atrophy on optical coherence tomography in the previous areas of retinal whitening. CONCLUSION: A Purtscher-like retinopathy with paracentral acute middle maculopathy and loss of vision may occur after filler injection below the neck, not just the face. This is the first report of vision loss caused by filler injected outside the face. PMID- 27552118 TI - OUTER RETINAL FOLDS FOLLOWING PARS PLANA VITRECTOMY WITH MEMBRANE PEEL. AB - PURPOSE: To report a case of outer retinal folds following pars plana vitrectomy with epiretinal membrane peel. METHODS: Retrospective case report. Spectral domain and en face optical coherence tomography findings are described. RESULTS: A 54-year-old man presented with distorted vision 1 month following pars plana vitrectomy with epiretinal membrane peel and subsequent cataract extraction. Optical coherence tomography of the affected eye revealed ripple-type and taco type outer retinal folds. En face optical coherence tomography illustrated a curvilinear characteristic pattern of the folds that spontaneously resolved with follow-up. CONCLUSION: The authors report a case of outer retinal folds developing in a patient following pars plana vitrectomy with membrane peel. En face optical coherence tomography findings of outer retinal folds may enhance diagnosis. PMID- 27552119 TI - HEMORRHAGIC OCCLUSIVE RETINAL VASCULITIS AND NONHEMORRHAGIC VASCULITIS AFTER UNCOMPLICATED CATARACT SURGERY WITH INTRACAMERAL VANCOMYCIN. AB - PURPOSE: To describe two cases of vasculitis: one hemorrhagic and one nonhemorrhagic after uncomplicated cataract surgery with intracameral vancomycin. METHODS: Retrospective case series. RESULTS: A 74-year-old female and a 54-year old female developed severe visual loss within 2 weeks of uncomplicated cataract surgery with intracameral vancomycin. The first patient developed a fulminant hemorrhagic vasculitis, whereas the second patient developed a less severe nonhemorrhagic vasculitis. Partial visual recovery and prevention of neovascular glaucoma was achieved using a combination of topical, oral, and intravitreal corticosteroids, along with intravitreal antivascular endothelial growth factor agents in the first patient and a combination of topical and oral corticosteroids alone in the second patient. CONCLUSION: Hemorrhagic occlusive retinal vasculitis and nonhemorrhagic vasculitis after uncomplicated cataract surgery with intracameral vancomycin have been rarely reported. Early recognition and treatment may prevent devastating visual outcomes. PMID- 27552120 TI - Area use and movements of the white croaker (Genyonemus lineatus) in the Los Angeles and Long Beach Harbors. AB - Understanding the movements of fish in relation to areas of contaminated and urbanized habitats is crucial to fisheries management and habitat remediation. In this study, the movements of white croaker in the Los Angeles and Long Beach Harbors were examined using both active and passive acoustic telemetry tracking. Daily area use for 20 fish actively tracked over multiple days averaged 94,720 +/ 78,720 m(2) (+/-SD), with daily activity spaces shifting over periods of up to 1 month. Long-term dispersal (up to 7 months) of 93 passively tracked white croaker followed significantly non-random patterns, with 55 individuals (59.1%) making inter-regional Harbor movements. Inter-regional movements took an average of 4.7 +/- 4.1 weeks to complete. Dispersal was significantly faster than what was predicted by an individual-based random walk model generated from short-term white croaker movements recorded during active tracking within the Harbor. Longer term dispersal is likely the result of intentional movements between patches of favorable habitat rather than random daily shifts in activity spaces, indicating that white croaker deliberately utilize different areas within the Harbor and over the course of a year utilize much of the favorable Harbor habitat. PMID- 27552121 TI - Decadal changes in zooplankton abundance and phenology of Long Island Sound reflect interacting changes in temperature and community composition. AB - Between 1939 and 1982, several surveys indicated that zooplankton in Long Island Sound, NY (LIS) appeared to follow an annual cycle typical of the Mid-Atlantic coast of North America. Abundance peaked in both early spring and late summer and the peaks were similar in magnitude. In recent decades, this cycle appeared to have shifted. Only one large peak tended to occur, and summer copepod abundance was consistently reduced by ~60% from 1939 to 1982 levels. In other Mid-Atlantic coastal systems such a dramatic shift has been attributed to the earlier appearance of ctenophores, particularly Mnemiopsis leidyi, during warmer spring months. However, over a decade of surveys in LIS have consistently found near zero values in M. leidyi biomass during spring months. Our multiple linear regression model indicates that summer M. leidyi biomass during this decade explains <25% of the variation in summer copepod abundance. During these recent, warmer years, summer copepod community shifts appear to explain the loss of copepod abundance. Although Acartia tonsa in 2010-2011 appeared to be present all year long, it was no longer the dominant summer zooplankton species. Warmer summers have been associated with an increase in cyanobacteria and flagellates, which are not consumed efficiently by A. tonsa. This suggests that in warming coastal systems multiple environmental and biological factors interact and likely underlie dramatic alterations to copepod phenology, not single causes. PMID- 27552122 TI - Development and validation of an ultrafast chromatographic method for quantification of the immunosuppressant mycophenolic acid in canine, feline and human plasma. AB - Mycophenolic acid (MPA) is the active metabolite of the prodrug mycophenolate mofetil. In this study, we developed and validated a novel ultra-high performance liquid chromatography (UHPLC) method for the rapid quantification of MPA in plasma from dogs, cats and humans. Following the protein precipitation, calibration standards and quality controls were separated by UHPLC reversed-phase on a 1.5MUm 2.1*100mmC18 column and quantified using UV detection at 215nm. The procedure produced a linear curve (r2>0.997) over the concentration range 0.4 50MUg/mL and exhibited a high degree of repeatability (CV% <11%). The limit of detection (LOD) and lower limit of quantitation (LLOQ) were 0.1 and <=0.4MUg/mL, respectively and the overall recovery was >=87%. By combining isocratic conditions with a UHPLC column containing solid core particles, we were able to elute MPA and the internal standard (mycophenolic acid carboxybutoxy ether) within 3.0min. The short total run time makes this method ideal to study the disposition of MPA in large batches of plasma samples and/or monitor plasma drug concentrations, as recommended for patients that require optimized immunosuppression. PMID- 27552123 TI - Estimating thickness of the inner dead-layer of n-type HPGe detector. AB - In this study, a procedure to estimate thickness of the inner dead-layer of an n type coaxial HPGe detector is described. Experimental measurements are carried out with standard point sources: (54)Mn, (57)Co, (60)Co, (88)Y, (109)Cd, (134)Cs, (137)Cs, and (152)Eu at distances of 5 and 10cm from source to detector. Shape and dimensions of a high-purity germanium (HPGe) detector are determined by radiography to characterize the geometry accurately for Monte Carlo simulation. The role of thickness of the inner dead-layer on full energy peak efficiency is illustrated by MCNP5 code, and it is observed that slope coefficient of efficiency curve has a linear relationship with thickness of the dead-layer. The adjustment of dead-layer yields good agreement, with relative deviation of <=3%, between experimental efficiency and simulated efficiency in the energy range of 88-1836keV. PMID- 27552124 TI - Neutronic and thermal-hydraulic analysis of new irradiation channels inside the Moroccan TRIGA Mark II research reactor core. AB - This study was conducted to improve the capacity of radioisotope production in the Moroccan TRIGA Mark II research reactor, which is considered as one of the most important applications of research reactors. The aim of this study is to enhance the utilization of TRIGA core in the field of neutron activation and ensure an economic use of the fuel. The main idea was to create an additional irradiation channel (IC) inside the core. For this purpose, three new core configurations are proposed, which differ according to the IC position in the core. Thermal neutron flux distribution and other neutronic safety parameters such as power peaking factors, excess reactivity, and control rods worth reactivity were calculated using the Monte Carlo N-Particle Transport (MCNP) code and neutron cross-section library based on ENDF/B-VII evaluation. The calculated thermal flux in the central thimble (CT) and in the added IC for the reconfigured core is compared with the thermal flux in the CT of the existing core, which is taken as a reference. The results show that all the obtained fluxes in CTs are very close to the reference value, while a remarkable difference is observed between the fluxes in the new ICs and reference. This difference depends on the position of IC in the reactor core. To demonstrate that the Moroccan TRIGA reactor could safely operate at 2MW, with new configurations based on new ICs, different safety-related thermal-hydraulic parameters were investigated. The PARET model was used in this study to verify whether the safety margins are met despite the new modifications of the core. The results show that it is possible to introduce new ICs safely in the reactor core, because the obtained values of the parameters are largely far from compromising the safety of the reactor. PMID- 27552125 TI - Values and costs in the management of psoriasis. PMID- 27552126 TI - Hierarchical Assembly of Cylindrical Block Comicelles Mediated by Spatially Confined Hydrogen-Bonding Interactions. AB - Hydrogen bonds are among the most common interactions used by nature for the creation of hierarchical structures from smaller building blocks. Herein, we describe an in-depth study of the hierarchical assembly of cylindrical block comicelles with a crystallizable poly(ferrocenyldimethylsilane) (PFS) core via H bonding interactions to form complex supermicellar structures. Well-defined block comicelles bearing H-bond donor (HD) segments (M(PFS-b-PMVSOH)), or H-bond acceptor (HA) segments (M(PFS-b-P2VP)), and non-interacting (N) segments (M(PFS-b PtBA)) were created by the living crystallization-driven self-assembly (CDSA) method [PMVSOH = hydroxyl-functionalized poly(methylvinylsiloxane), P2VP = poly(2 vinylpyridine), PtBA = poly(tert-butyl acrylate), M = micelle segment]. Due to the control provided by the living CDSA approach, both the block comicelles and the individual segments were virtually monodisperse in length, which facilitated their predictable hierarchical assembly into higher-level structures. Two cases were investigated in detail: first, the interaction of N-HA-N triblock comicelles with the HD homopolymer PMVSOH, and second, the interaction of N-HD-N triblock comicelles with very short HA cylinders (seeds). By manipulation of several factors, namely coronal steric effects (via the PtBA corona chain) and attractive interaction strength (via the H-bonding interaction between P2VP and PMVSOH), the aggregation of the triblock comicelles could be controlled, and well-defined multi-micrometer-size structures such as "shish-kebab"-shaped supermicelles were prepared. The ability of the seeds adsorbed on the block comicelles to function as initiators for living CDSA to generate fence-like "shish-kebab" superstructures was also explored. PMID- 27552127 TI - Emerging medication for the treatment of male hypogonadism. AB - INTRODUCTION: Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. AREAS COVERED: The available literature of T and alternative treatments for male hypogonadism are discussed. EXPERT OPINION: Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence. PMID- 27552129 TI - Evaluation of human pharmaceutical emissions and concentrations in Swedish river basins. AB - An emissions inventory for top consumed human pharmaceuticals in Sweden was done based on national consumption data, human metabolic rates and wastewater treatment removal rates. Concentrations of pharmaceuticals in surface waters in Swedish river basins were predicted using estimated emissions from the inventory and river discharges. Our findings indicate that the top ten emitted pharmaceuticals in our study set of 54 substances are all emitted in amounts above 0.5ton/y to both surface waters and soils. The highest emissions to water were in decreasing order for Metformin, Furosemide, Gabapentin, Atenolol and Tramadol. Predicted emissions to soils calculated with the knowledge that in Sweden sludge is mostly disposed to soil, point to the highest emissions among the studied drugs coming from, in decreasing order, Metformin, Paracetamol, Ibuprofen, Gabapentin and Atenolol. Surface water concentrations in Sweden's largest rivers, all located in low density population zones, were found to be below 10ng/L for all substances studied. In contrast, concentrations in surface waters in Stockholm's metropolitan area, the most populous in Sweden, surpassed 100ng/L for four substances: Atenolol, Metformin, Furosemide and Gabapentin. PMID- 27552128 TI - Evaluation of anionic surfactant concentrations in US effluents and probabilistic determination of their combined ecological risk in mixing zones. AB - Alcohol sulfates (AS), alcohol ethoxysulfates (AES), linear alkyl benzenesulfonates (LAS) and methyl ester sulfonates (MES) are anionic surfactants that are widely used in household detergents and consumer products resulting in over 1 million tons being disposed of down the drain annually in the US. A monitoring campaign was conducted which collected grab effluent samples from 44 wastewater treatment plants (WWTPs) across the US to generate statistical distributions of effluent concentrations for anionic surfactants. The mean concentrations for AS, AES, LAS and MES were 5.03+/-4.5, 1.95+/-0.7, 15.3+/-19, and 0.35+/-0.13MUg/L respectively. Since each of these surfactants consist of multiple homologues that differ in their toxicity, the concentration of each homologue measured in an effluent sample was converted into a toxic unit (TU) by normalizing to the predicted no effect concentration (PNEC) derived from high tier effects data (mesocosm studies). The statistical distributions of the combined TUs in the effluents were used in combination with distributions of dilution factors for WWTP mixing zones to conduct a US-wide probabilistic risk assessment for the aquatic environment for each of the surfactants. The 90th percentile level of TUs for AS, AES, LAS and MES in mixing zones were 1.89*10-2, 2.73*10-3, 2.72*10-2, and 3.65*10-5 under 7Q10 (lowest river flow occurring over a 7day period every 10years) low flow conditions. Because these surfactants have the same toxicological mode of action, the TUs were summed and the aquatic safety for anionic surfactants as a whole was assessed. At the 90th percentile level under the conservative 7Q10 low flow conditions the forecasted TUs were 4.21*10-2 which indicates that there is a significant margin of safety for the class of anionic surfactants in US aquatic environments. PMID- 27552130 TI - Potamodromous fish movements under multiple stressors: Connectivity reduction and oxygen depletion. AB - Rivers are impacted by multiple stressors that can interact to create synergistic, additive or antagonistic effects, but experimental studies on fish encompassing more than one stressor are seldom found. Thus, there is the need to study stressors through multifactorial approaches that analyse the impact of fish exposure to multiple stressors and evaluate fish sensitivity to stressor combinations. Some of the most common impacts to Mediterranean rivers are of two natures: i) water abstraction and ii) diffuse pollution. Therefore, the present study aims at studying the responses of potamodromous fish facing combinations of: 1) a primary stressor (two levels of connectivity reduction due to water scarcity), and 2) a secondary stressor (three levels of oxygen depletion due to increase organic load - of anthropogenic nature). Schools of five wild fish from a cyprinid species (Luciobarbus bocagei) were placed in a flume, equipped with see-through sidewalls to allow for behavioural analysis, and subjected to different combinations of the stressors. Results show that at the unconnected level the primary stressor (lack of connectivity) overrode the effect of the secondary stressor (oxygen depletion), but when connectivity existed oxygen depletion caused a reduction of fish movements with decreasing oxygen concentrations. This multifactorial study contributes to improved prediction of fish responses upon actual or projected pressure scenarios. PMID- 27552131 TI - Global assessment of nitrogen losses and trade-offs with yields from major crop cultivations. AB - Agricultural application of reactive nitrogen (N) for fertilization is a cause of massive negative environmental problems on a global scale. However, spatially explicit and crop-specific information on global N losses into the environment and knowledge of trade-offs between N losses and crop yields are largely lacking. We use a crop growth model, Python-based Environmental Policy Integrated Climate (PEPIC), to determine global N losses from three major food crops: maize, rice, and wheat. Simulated total N losses into the environment (including water and atmosphere) are 44TgNyr-1. Two thirds of these, or 29TgNyr-1, are losses to water alone. Rice accounts for the highest N losses, followed by wheat and maize. The N loss intensity (NLI), defined as N losses per unit of yield, is used to address trade-offs between N losses and crop yields. The NLI presents high variation among different countries, indicating diverse N losses to produce the same amount of yields. Simulations of mitigation scenarios indicate that redistributing global N inputs and improving N management could significantly abate N losses and at the same time even increase yields without any additional total N inputs. PMID- 27552132 TI - An appraisal of the sediment yield in western Mediterranean river basins. AB - The number of studies assessing soil erosion and sediment transport has increased with the aim of achieving sustainable land and water management. Mediterranean rivers have been the object of many of these studies due to their naturally high values of sediment fluxes and a higher vulnerability under future climate scenarios. In this context, we attempt to use empirical relationships to (i) further assess the relation between sediment yield and basin scale and (ii) provide an update on the main drivers controlling sediment yield in these particular river systems. For this purpose, sediment yield data (from reservoir sedimentation surveys and sediment transport records) was collected from >100 locations distributed across the western Mediterranean area, with basin areas ranging from 1 to 100,000km2. Quantile Regression analysis was used to assess the correlation between basin area and sediment yield, while additional basin-scale descriptors were related to sediment yield by means of multiple regression analysis. Results showed the complexity in the relationship between basin scale and sediment yield, with changes in supply conditions with increasing area introducing uncertainties in the correlation. Despite the large scatter, analysis pointed towards the same direction and area appeared to be the main constrain for the maximum value of sediment yield that can be found at a specific basin scale. Results from the multiple regression indicated that variables representing basin's physiography, climate and land use were highly correlated with the basins' sediment yield. Also, a better model performance was obtained when using total sediment yield instead of specific values (per unit area). Validation showed model instability, potentially due to data limitations and the use of catchments with varying characteristics. Overall, despite providing some insights on the correlation between sediment yield and basin-scale characteristics, validation prevented direct extrapolation of the model to other catchments. PMID- 27552133 TI - Radiofrequency radiation injures trees around mobile phone base stations. AB - In the last two decades, the deployment of phone masts around the world has taken place and, for many years, there has been a discussion in the scientific community about the possible environmental impact from mobile phone base stations. Trees have several advantages over animals as experimental subjects and the aim of this study was to verify whether there is a connection between unusual (generally unilateral) tree damage and radiofrequency exposure. To achieve this, a detailed long-term (2006-2015) field monitoring study was performed in the cities of Bamberg and Hallstadt (Germany). During monitoring, observations and photographic recordings of unusual or unexplainable tree damage were taken, alongside the measurement of electromagnetic radiation. In 2015 measurements of RF-EMF (Radiofrequency Electromagnetic Fields) were carried out. A polygon spanning both cities was chosen as the study site, where 144 measurements of the radiofrequency of electromagnetic fields were taken at a height of 1.5m in streets and parks at different locations. By interpolation of the 144 measurement points, we were able to compile an electromagnetic map of the power flux density in Bamberg and Hallstadt. We selected 60 damaged trees, in addition to 30 randomly selected trees and 30 trees in low radiation areas (n=120) in this polygon. The measurements of all trees revealed significant differences between the damaged side facing a phone mast and the opposite side, as well as differences between the exposed side of damaged trees and all other groups of trees in both sides. Thus, we found that side differences in measured values of power flux density corresponded to side differences in damage. The 30 selected trees in low radiation areas (no visual contact to any phone mast and power flux density under 50MUW/m2) showed no damage. Statistical analysis demonstrated that electromagnetic radiation from mobile phone masts is harmful for trees. These results are consistent with the fact that damage afflicted on trees by mobile phone towers usually start on one side, extending to the whole tree over time. PMID- 27552134 TI - Electrothermal Annealing (ETA) Method to Enhance the Electrical Performance of Amorphous-Oxide-Semiconductor (AOS) Thin-Film Transistors (TFTs). AB - An electro-thermal annealing (ETA) method, which uses an electrical pulse of less than 100 ns, was developed to improve the electrical performance of array-level amorphous-oxide-semiconductor (AOS) thin-film transistors (TFTs). The practicality of the ETA method was experimentally demonstrated with transparent amorphous In-Ga-Zn-O (a-IGZO) TFTs. The overall electrical performance metrics were boosted by the proposed method: up to 205% for the trans-conductance (gm), 158% for the linear current (Ilinear), and 206% for the subthreshold swing (SS). The performance enhancement were interpreted by X-ray photoelectron microscopy (XPS), showing a reduction of oxygen vacancies in a-IGZO after the ETA. Furthermore, by virtue of the extremely short operation time (80 ns) of ETA, which neither provokes a delay of the mandatory TFTs operation such as addressing operation for the display refresh nor demands extra physical treatment, the semipermanent use of displays can be realized. PMID- 27552135 TI - 3 Screen ELISA for High-Throughput Detection of Beta Cell Autoantibodies in Capillary Blood. AB - BACKGROUND: Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) to identify children positive for multiple beta cell autoantibodies. METHODS: An ELISA format was used where plates were coated with a mixture of recombinant GAD, IA-2, and ZnT8325W/R-dimer molecules. The performance was determined in venous blood from 686 first-degree relatives of patients with type 1 diabetes, and 200 patients at onset of type 1 diabetes, and applied as a screening assay in capillary blood from 33,639 general population children. RESULTS: The 3 Screen assay sensitivity for detecting autoantibody-positive patients at onset of type 1 diabetes was similar to that achieved by separate radiobinding assays (RBAs) for antibodies to GAD, IA-2, and ZnT8. Results in venous and capillary serum were correlated (R = 0.987). At a threshold corresponding to the 98th centile (29.1 U/mL) of all 33,639 capillary samples, the 3 Screen was positive in 123 samples with two or more RBA-positive antibodies to insulin, GAD, IA-2, or ZnT8, 146 with one antibody, and 479 that were RBA negative for beta cell autoantibodies. CONCLUSION: A 3 Screen ELISA was developed that was suitable for first step screening of multiple beta cell autoantibodies in capillary blood. PMID- 27552136 TI - The role of navigation instruction at intersections for older drivers and those with early Alzheimer's disease. AB - AIMS: Our purpose was to explore the effect of navigation instruction on older drivers' driving performance at left turn intersections. Left turns at intersections are particularly complex because they require many perceptive and cognitive abilities under considerable time pressure. METHODS: Fifty-four participants were recruited: 18 drivers with early-stage Alzheimer's disease (AD), 18 neurologically healthy older drivers and 18 younger individuals. Various cognitive processes were measured, and 9 left turn maneuvers with or without navigation instruction were evaluated during an in-traffic road test. The psychomotor, planning and decision-making components involved in left turn were also analyzed closely. RESULTS: Only older drivers (both healthy drivers and those with AD) were negatively affected by navigation instruction during the maneuver. The planning and decision-making components were more likely to be affected by the navigation instruction. CONCLUSION: This finding highlights the importance of carefully considering the use of navigation instructions when developing navigation systems. Adapting this instruction is necessary to simplify our understanding of the real-world driving environment and to avoid increasing the cognitive load of older drivers. PMID- 27552137 TI - What you get from what you see: Parametric assessment of visual processing capacity in multiple sclerosis and its relation to cognitive fatigue. AB - Multiple sclerosis (MS(1)) is a diffusely disseminated inflammatory disease affecting widespread cerebral networks. Major cognitive impairments are a reduction of processing capacity and mental fatigue, i.e., an "abnormal sense of tiredness or lack of energy". Here, the present study provides the first assessment of the distinct components of visual processing capacity based on a 'theory of visual attention' (TVA(2)) in MS patients and relates it to measures of subjective as well as (more) objective fatigue. The performance of 36 relapsing-remitting MS patients in a whole report task of brief letter arrays was compared to healthy control subjects matched for gender, age and education. Additionally, the sustained attention test PASAT-3(3) served as a measure of objective fatigue, and the self-report questionnaire MFIS(4) as a measure of subjective fatigue. Results indicate generally diminished processing speed as well as iconic memory buffers, and increased perceptual thresholds in MS patients compared to healthy controls. Block-wise analysis of attentional parameters shows that the processing speed performance of MS patients declines in the second half of the TVA-based test compared to healthy controls and in particular for patients with high versus low objective fatigue. These findings describe which aspects of processing capacity are impaired in MS, and show that fatigue mainly affects speed of processing. Thus, TVA-based assessment provides a novel approach in the determination of cognitive impairments and fatigue in MS. However, further research is required to elucidate the complex relations of processing capacity and cognitive functions in MS. PMID- 27552138 TI - The role of surgery in metastatic squamous cell carcinoma of the penis. AB - PURPOSE OF REVIEW: Prognosis of penile squamous cell cancer (PeSCC) depends on the involvement of the groin(s) as first step. We introduce the current available evidences that should rule the use of surgery in the management of PeSCC. RECENT FINDINGS: Prophylactic inguinal node dissection in patients with no palpable nodes associates with immediate and long-term side-effects in up to 70% of patients. Recent findings support selective intervention based on early identification of dynamic sentinel node biopsy (DSNB) with false negative rate of 4-12%. Adequate node retrieval and extending surgery to the pelvis have been addressed as important key factors as staging and therapeutic factors in patients with nodal metastases. Pelvic dissections could be spared only in patients with small (< 3 cm), limited (< 3 nodes) and no extranodal extension. Bilateral pelvic dissection should be recommended in case of involvement of bilateral nodes of at least four. Cisplatin-based neo-adjuvant chemotherapy has a moderate activity, whereas adjuvant chemotherapy associates with prolonged survival in a proportion of patients. SUMMARY: In case of nodal metastases, surgery still represents the most effective treatment. Preventive surgery could be driven by DSNB, which needs an accurate multistep pathway. Extent of surgery is of paramount importance, and inguinal only and unilateral dissections should be reserved to selected patients with the most favorable features. Definitive conclusions concerning perioperative chemotherapy cannot be drawn. PMID- 27552139 TI - Immunotherapy with radiotherapy in urological malignancies. AB - PURPOSE OF REVIEW: Radiotherapy has the potential to augment the host's immune response to cancer. Urological malignancies are highly immunogenic and the combination of radiotherapy and immunotherapy shows promise. In this review, we discuss the effects of radiotherapy on the cancer immune system and highlight the rationale for using the combined approach in prostate, urothelial and renal cancers. Current clinical studies are summarized emphasising the synergistic effects of the combination and the possibility of improved clinical outcomes. RECENT FINDINGS: Local and abscopal effects have been observed in different urological cancers when using a combined approach. Large fraction size is associated with an increased immune response. Multiple radiotherapy/immunotherapy combinations are being studied in several clinical trials although no combination has yet been introduced in to standard practice. SUMMARY: Although our knowledge of immunomodulation by radiotherapy has improved significantly in recent times, there remain several unanswered questions regarding how to best use the combination in clinical practice. Ongoing trials will provide further insight into complex mechanisms governing radiotherapy-immunotherapy interactions, with potential to improve clinical outcomes. PMID- 27552140 TI - Surgical resection of metastases in patients with urogenital malignancies. PMID- 27552141 TI - Selective Adsorption of Thiols Using Gold Nanoparticles Supported on Metal Oxides. AB - Selective capture of thiols from a synthetic hydrogen sulfide containing mixture using supported nanogold materials has been explored for the potential removal of thiols from sour gas production fluids. In this research, TiO2-, Al2O3-, SiO2-, and ZnO-supported gold nanoparticles have been studied for their usage as regeneratable adsorbents to capture CH3SH, C2H5SH, and i-C3H7SH. Au/TiO2 and Au/Al2O3 showed promising properties for removing the thiols efficiently from a gas-phase mixture; however, Au/Al2O3 did catalyze some undesirable side reactions, e.g., carbonyl sulfide formation. It was found that a mild temperature of T = 200 degrees C was sufficient for regeneration of either Au/TiO2 or Au/Al2O3 adsorbent. The metal oxide mesopores played an important role for accommodating gold particles and chemisorption of the thiols, where smaller pore sizes were found to inhibit the agglomeration/growth of gold particles. The nature of thiol adsorption and the impact of multiple adsorption-desorption cycles on the adsorbents have been studied using electron microscopy, XPS, XRD, GC, and physi/chemiadsorption analyses. PMID- 27552142 TI - Society of Biomolecular Imaging and Informatics Special Issue. PMID- 27552143 TI - Assessing Drug Efficacy in a Miniaturized Pancreatic Cancer In Vitro 3D Cell Culture Model. AB - Pancreatic cancer continues to have one of the poorest prognoses among all cancers. The drug discovery efforts for this disease have largely failed, with no significant improvement in survival outcomes for advanced pancreatic cancer patients over the past 20 years. Traditional in vitro cell culture techniques have been used extensively in both basic and early drug discovery; however, these systems offer poor models to assess emerging therapeutics. More predictive cell based models, which better capture the cellular heterogeneity and complexities of solid pancreatic tumors, are urgently needed not only to improve drug discovery success but also to provide insight into the tumor biology. Pancreatic tumors are characterized by a unique micro-environment that is surrounded by a dense stroma. A complex network of interactions between extracellular matrix (ECM) components and the effects of cell-to-cell contacts may enhance survival pathways within in vivo tumors. This biological and physical complexity is lost in traditional cell monolayer models. To explore the predictive potential of a more complex cellular system, a three-dimensional (3D) micro-tumor assay was evaluated. Efficacy of six current chemotherapeutics was determined against a panel of primary and metastatic pancreatic tumor cell lines in a miniaturized ECM-based 3D cell culture system. Suitability for potential use in high-throughput screening applications was assessed, including ascertaining the effects that miniaturization and automation had on assay robustness. Cellular health was determined by utilizing an indirect population-based metabolic activity assay and a direct imaging-based cell viability assay. PMID- 27552144 TI - Development of the Theta Comparative Cell Scoring Method to Quantify Diverse Phenotypic Responses Between Distinct Cell Types. AB - In this article, we have developed novel data visualization tools and a Theta comparative cell scoring (TCCS) method, which supports high-throughput in vitro pharmacogenomic studies across diverse cellular phenotypes measured by multiparametric high-content analysis. The TCCS method provides a univariate descriptor of divergent compound-induced phenotypic responses between distinct cell types, which can be used for correlation with genetic, epigenetic, and proteomic datasets to support the identification of biomarkers and further elucidate drug mechanism-of-action. Application of these methods to compound profiling across high-content assays incorporating well-characterized cells representing known molecular subtypes of disease supports the development of personalized healthcare strategies without prior knowledge of a drug target. We present proof-of-principle data quantifying distinct phenotypic response between eight breast cancer cells representing four disease subclasses. Application of the TCCS method together with new advances in next-generation sequencing, induced pluripotent stem cell technology, gene editing, and high-content phenotypic screening are well placed to advance the identification of predictive biomarkers and personalized medicine approaches across a broader range of disease types and therapeutic classes. PMID- 27552145 TI - Combining High-Content Imaging and Phenotypic Classification Analysis of Senescence-Associated Beta-Galactosidase Staining to Identify Regulators of Oncogene-Induced Senescence. AB - Hyperactivation of the PI3K/AKT/mTORC1 signaling pathway is a hallmark of the majority of sporadic human cancers. Paradoxically, chronic activation of this pathway in nontransformed cells promotes senescence, which acts as a significant barrier to malignant progression. Understanding how this oncogene-induced senescence is maintained in nontransformed cells and conversely how it is subverted in cancer cells will provide insight into cancer development and potentially identify novel therapeutic targets. High-throughput screening provides a powerful platform for target discovery. Here, we describe an approach to use RNAi transfection of a pre-established AKT-induced senescent cell population and subsequent high-content imaging to screen for senescence regulators. We have incorporated multiparametric readouts, including cell number, proliferation, and senescence-associated beta-galactosidase (SA-betaGal) staining. Using machine learning and automated image analysis, we also describe methods to classify distinct phenotypes of cells with SA-betaGal staining. These methods can be readily adaptable to high-throughput functional screens interrogating the mechanisms that maintain and prevent senescence in various contexts. PMID- 27552146 TI - SBI(2) High Content 2016, 3(rd) Annual Conference, September 12(th)-14(th). PMID- 27552148 TI - Heterogeneous Phase Transfer Catalysis in Solid Phase Syntheses of Anth-Cyclic Tetrapeptides. AB - This study features solid phase syntheses of cyclic tetrapeptides containing anthranilic acid (Anth) on relatively inexpensive resins derived from polystyrene. It proved to be difficult to hydrolyze a supported Anth-methyl ester unless a phase transfer catalyst was added to facilitate transport of hydroxide into the swollen hydrophobic gel state of the resin. We suggest this may be an under-appreciated strategy for improving syntheses on polystyrene supports. PMID- 27552147 TI - Long-Term Outcomes Associated with Traumatic Brain Injury in Childhood and Adolescence: A Nationwide Swedish Cohort Study of a Wide Range of Medical and Social Outcomes. AB - BACKGROUND: Traumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated with adult mortality, psychiatric morbidity, and social outcomes. METHODS AND FINDINGS: In a Swedish birth cohort between 1973 and 1985 of 1,143,470 individuals, we identified all those who had sustained at least one TBI (n = 104,290 or 9.1%) up to age 25 y and their unaffected siblings (n = 68,268) using patient registers. We subsequently assessed these individuals for the following outcomes using multiple national registries: disability pension, specialist diagnoses of psychiatric disorders and psychiatric inpatient hospitalisation, premature mortality (before age 41 y), low educational attainment (not having achieved secondary school qualifications), and receiving means-tested welfare benefits. We used logistic and Cox regression models to quantify the association between TBI and specified adverse outcomes on the individual level. We further estimated population attributable fractions (PAF) for each outcome measure. We also compared differentially exposed siblings to account for unobserved genetic and environmental confounding. In addition to relative risk estimates, we examined absolute risks by calculating prevalence and Kaplan-Meier estimates. In complementary analyses, we tested whether the findings were moderated by injury severity, recurrence, and age at first injury (ages 0-4, 5-9, 6-10, 15-19, and 20-24 y). TBI exposure was associated with elevated risks of impaired adult functioning across all outcome measures. After a median follow up period of 8 y from age 26 y, we found that TBI contributed to absolute risks of over 10% for specialist diagnoses of psychiatric disorders and low educational attainment, approximately 5% for disability pension, and 2% for premature mortality. The highest relative risks, adjusted for sex, birth year, and birth order, were found for psychiatric inpatient hospitalisation (adjusted relative risk [aRR] = 2.0; 95% CI: 1.9-2.0; 6,632 versus 37,095 events), disability pension (aRR = 1.8; 95% CI: 1.7-1.8; 4,691 versus 29,778 events), and premature mortality (aRR = 1.7; 95% CI: 1.6-1.9; 799 versus 4,695 events). These risks were only marginally attenuated when the comparisons were made with their unaffected siblings, which implies that the effects of TBI were consistent with a causal inference. A dose-response relationship was observed with injury severity. Injury recurrence was also associated with higher risks-in particular, for disability pension we found that recurrent TBI was associated with a 3-fold risk increase (aRR = 2.6; 95% CI: 2.4-2.8) compared to a single-episode TBI. Higher risks for all outcomes were observed for those who had sustained their first injury at an older age (ages 20-24 y) with more than 25% increase in relative risk across all outcomes compared to the youngest age group (ages 0-4 y). On the population level, TBI explained between 2%-6% of the variance in the examined outcomes. Using hospital data underestimates milder forms of TBI, but such misclassification bias suggests that the reported estimates are likely conservative. The sibling-comparison design accounts for unmeasured familial confounders shared by siblings, including half of their genes. Thus, residual genetic confounding remains a possibility but will unlikely alter our main findings, as associations were only marginally attenuated within families. CONCLUSIONS: Given our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents. PMID- 27552149 TI - Tacalcitol: a useful adjunct to narrow-band ultraviolet-B phototherapy in vitiligo. AB - BACKGROUND: Phototherapy especially narrow-band UV-B (NBUVB) has been considered as mainstay of therapy in nonsegmental vitiligo (generalized type). Topical tacalcitol has also been claimed to be effective, either as monotherapy or as combination therapy. PURPOSE: Comparison of clinical efficacy and safety of NBUVB in combination with topical tacalcitol vs. NBUVB alone in vitiligo. MATERIAL & METHODS: Thirty patients with symmetrical vitiliginous lesions were enrolled for 24 weeks. Patients were instructed to apply tacalcitol ointment on right side of body once daily. In addition, the whole body was irradiated with NBUVB thrice weekly. All the patients were examined, and lesional photography was done. Patients were also followed up for 6 months post-treatment. RESULTS: Our study resulted in two key findings: (1) There was a statistically significant difference in mean percentage of repigmentation at 8, 16 and 24 weeks between combination therapy and NBUVB. (2) The mean cumulative dose and number of treatment sessions for initial repigmentation were significantly lower with combination therapy. No serious adverse effects were observed during the study period. CONCLUSION: Topical tacalcitol potentiates efficacy of NBUVB as it enhances extent of pigmentation, decrease time to repigmentation and lowers the cumulative doses of NBUVB, thereby leading to greater patient satisfaction and improved compliance. PMID- 27552150 TI - Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development. AB - The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD) and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT) imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS) between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis. PMID- 27552152 TI - Brief Report: Differential Effects of Tenofovir, Abacavir, Emtricitabine, and Darunavir on Telomerase Activity In Vitro. AB - In vitro, tenofovir and abacavir induced a significant dose-dependent inhibition of telomerase activity at therapeutic concentrations in peripheral blood mononuclear cells of healthy subjects. Median inhibition of telomerase activity by tenofovir at 0.5 and 1 MUM was 29% [Interquartile range (IQR) 29%-34%, P = 0.042] and 28% (IQR 28%-41%, P = 0.042), respectively. Abacavir inhibition was 12% (IQR 9%-13%, P = 0.043) at 3 MUM and 14% (IQR 10%-29%, P = 0.043) at 10 MUM. Tenofovir and abacavir did not change human telomerase reverse transcriptase (hTERT) levels or mRNA levels of other telomerase complex genes. Exposure to emtricitabine or darunavir did not affect telomerase activity, hTERT protein levels, or mRNA levels of telomerase/shelterin genes. PMID- 27552151 TI - Cardiovascular Risk Factors of Adults Age 20-49 Years in the United States, 1971 2012: A Series of Cross-Sectional Studies. AB - BACKGROUND: The health of younger adults in the U.S. has important public health and economic-related implications. However, previous literature is insufficient to fully understand how the health of this group has changed over time. This study examined generational differences in cardiovascular risk factors of younger adults over the past 40 years. METHODS: Data were from 6 nationally representative cross-sectional National Health and Nutrition Examination Surveys (1971-2012; N = 44,670). Participants were adults age 20-49 years who self reported sociodemographic characteristics and health conditions, and had examination/laboratory measures for hypertension, hyperlipidemia, diabetes, obesity, and chronic kidney disease. Prevalences of sociodemographic characteristics and health status were determined by study period. Logistic regression was used to determine the odds [odds ratio (OR), 95% confidence interval] of health conditions by study period: models adjusted only for age, sex, and race, and fully adjusted models additionally adjusted for socioeconomic characteristics, smoking, BMI, diabetes, and/or hypertension (depending on the outcome) were assessed. RESULTS: Participants in 2009-2012 were significantly more likely to be obese and have diabetes compared to those in 1971-1975 (OR = 4.98, 3.57-6.97; OR = 3.49, 1.59-7.65, respectively, fully adjusted). Participants in 2009-2012 vs. 1988-1994 were significantly more likely to have had hypertension but uncontrolled hypertension was significantly less likely (OR = 0.67, 0.52-0.86, fully adjusted). There was no difference over time for high cholesterol, but uncontrolled high cholesterol was significantly less likely in 2009-2012 vs. 1988-1994 (OR = 0.80, 0.68-0.94, fully adjusted). The use of hypertensive and cholesterol medications increased while chronic kidney and cardiovascular diseases were relatively stable. CONCLUSIONS: Cardiovascular risk factors of younger U.S. adults have worsened over the past 40 years, but treatment for hypertension and high cholesterol has improved. The sub-optimal and worsening health in younger adults may have a substantial impact on health care utilization and costs, and should be considered when developing health care practices. PMID- 27552153 TI - Brief Report: Factors Associated With the Selection of Initial Antiretroviral Therapy From 2009 to 2012. AB - We examined factors associated with selection of initial antiretroviral regimen in the CNICS cohort. Patients initiating antiretroviral therapy between July 2009 and December 2012 were classified as receiving a nonnucleoside reverse transcriptase inhibitor (NNRTI)-, boosted protease inhibitor (PI)-, or raltegravir-based regimen. Among 873 patients initiating antiretroviral therapy, 488 regimens contained an NNRTI, 319 a boosted PI, and 66 raltegravir. Patients with depression and women were less likely to receive an NNRTI, whereas those with underlying cardiovascular disease, liver disease, and those coinfected with hepatitis C were more likely to receive raltegravir. Those with baseline viral load >100,000 c/ml and those with substance use were more likely to receive a boosted PI. Thus, in the "real world," ARV regimen choices appear to take into account adverse effects and patient baseline characteristics. Factors that impact initial regimen selection will likely become more heterogeneous over time as more choices for HIV therapy become available. PMID- 27552154 TI - MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. AB - The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV 2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate. PMID- 27552156 TI - Brief Report: The Right People, Right Places, and Right Practices: Disparities in PrEP Access Among African American Men, Women, and MSM in the Deep South. AB - Disproportionate rates of HIV are observed in Black women and men, especially in the Southern United States. We observed limited uptake of preexposure prophylaxis (PrEP) services in our Southern community among these groups, particularly Black men who have sex with men relative to new HIV cases in Birmingham, AL; 18% accessed PrEP services compared with 50% of new HIV cases. Further research is needed to understand PrEP access and uptake in high-risk populations. PMID- 27552155 TI - High Treatment Success Rates Among HIV-Infected Multidrug-Resistant Tuberculosis Patients After Expansion of Antiretroviral Therapy in Botswana, 2006-2013. AB - BACKGROUND: Few studies have examined multidrug-resistant (MDR) tuberculosis (TB) treatment outcomes among HIV-infected persons after widespread expansion of antiretroviral therapy (ART). We describe MDR-TB treatment outcomes among HIV infected and HIV-uninfected patients in Botswana after ART expansion. METHODS: We retrospectively reviewed data from patients who started MDR-TB therapy in Botswana during 2006-2013. Multivariable regression models were used to compare treatment outcomes between HIV-infected and HIV-uninfected patients. RESULTS: We included 588 MDR-TB patients in the analysis, of whom, 47 (8.0%) and 9 (1.5%) were diagnosed with pre-extensively drug-resistant (XDR)-TB and XDR-TB, respectively. Of the 408 (69.4%) HIV-infected patients, 352 (86.0%) were on ART or started ART during treatment, and median baseline CD4 T-cell count was 234 cells/mm. Treatment success rates were 79.4% and 73.0% among HIV-uninfected and HIV-infected patients, respectively (P = 0.121). HIV-infected patients with CD4 T cell count <100 cells/mm were more likely to die during treatment compared with HIV-uninfected patients (adjusted risk ratio = 1.890; 95% CI: 1.098 to 3.254). CONCLUSIONS: High rates of treatment success were achieved with programmatic management of MDR-TB and HIV in Botswana after widespread expansion of ART. However, a 2-fold increase in mortality was observed among HIV-infected persons with baseline CD4 <100 cells/mm compared with HIV-uninfected persons. PMID- 27552157 TI - Strong ifitm1 Expression in CD4 T Cells in HIV Controllers Is Correlated With Immune Activation. PMID- 27552158 TI - Brief Report: PrEP Uptake, Adherence, and Discontinuation Among California YMSM Using Geosocial Networking Applications. AB - We investigated pre-exposure prophylaxis (PrEP) uptake, adherence, and discontinuation among young app-using men who have sex with men in California (N = 761). Approximately, 9.7% of participants had ever used PrEP; 87% of those deemed good candidates for screening (indicated by a Centers for Disease Control and Prevention risk index score >=10) were not current or past users. PrEP use was associated with higher income [adjusted odds ratio (aOR): 4.13; confidence interval (CI): 1.87 to 9.12], receptive condomless anal sex (aOR: 3.41; CI: 1.71 to 6.78), HIV-positive sex partners (aOR: 2.87; CI: 1.53 to 5.38), popper use (aOR: 3.47; CI: 1.96 to 6.13), and recent sexually transmitted infection diagnosis (aOR: 2.90; CI: 1.64 to 5.13). Some users (41.5%) wanted help remembering to take PrEP. The top reason for discontinuation was concern about long-term side effects (33.0%). Young men who have sex with men app users are prime candidates for PrEP, despite low uptake. Apps may be useful tools for PrEP information dissemination, adherence monitoring, and support. PMID- 27552159 TI - Mechanic and surface properties of central-venous port catheters after removal: A comparison of polyurethane and silicon rubber materials. AB - Central venous port devices made of two different polymeric materials, thermoplastic polyurethane (TPU) and silicone rubber (SiR), were compared due their material properties. Both naive catheters as well as catheters after removal from patients were investigated. In lab experiments the influence of various chemo-therapeutic solutions on material properties was investigated, whereas the samples after removal were compared according to the implanted time in patient. The macroscopic, mechanical performance was assessed with dynamic, specially adapted tests for elasticity. The degradation status of the materials was determined with common tools of polymer characterisation, such as infrared spectroscopy, molecular weight measurements and various methods of thermal analysis. The surface morphology was analysed using scanning electron microscopy. A correlation between material properties and clinical performance was proposed. The surface morphology and chemical composition of the polyurethane catheter materials can potentially result in increased susceptibility of the catheter to bloodstream infections and thrombotic complications. The higher mechanic failure, especially with increasing implantation time of the silicone catheters is related to the lower mechanical performance compared to the polyurethane material as well as loss of barium sulphate filler particles near the surface of the catheter. This results in preformed microscopic notches, which act as predetermined sites of fracture. PMID- 27552160 TI - Microbial Morphology and Motility as Biosignatures for Outer Planet Missions. AB - Meaningful motion is an unambiguous biosignature, but because life in the Solar System is most likely to be microbial, the question is whether such motion may be detected effectively on the micrometer scale. Recent results on microbial motility in various Earth environments have provided insight into the physics and biology that determine whether and how microorganisms as small as bacteria and archaea swim, under which conditions, and at which speeds. These discoveries have not yet been reviewed in an astrobiological context. This paper discusses these findings in the context of Earth analog environments and environments expected to be encountered in the outer Solar System, particularly the jovian and saturnian moons. We also review the imaging technologies capable of recording motility of submicrometer-sized organisms and discuss how an instrument would interface with several types of sample-collection strategies. Key Words: In situ measurement Biosignatures-Microbiology-Europa-Ice. Astrobiology 16, 755-774. PMID- 27552161 TI - Allelopathy of Bracken Fern (Pteridium arachnoideum): New Evidence from Green Fronds, Litter, and Soil. AB - The neotropical bracken fern Pteridium arachnoideum (Kaulf.) Maxon. (Dennstaedtiaceae) is described as an aggressive pioneer plant species. It invades abandoned or newly burned areas and represents a management challenge at these invaded sites. Native to the Atlantic Forest and Cerrado (Tropical Savanna) Brazilian biomes, P. arachnoideum has nevertheless become very problematic in these conservation hotspots. Despite some reports suggesting a possible role of allelopathy in this plant's dominance, until now there has been little evidence of isolated and individually identified compounds with phytotoxic activities present in its tissues or in the surrounding environment. Thus, the aim of this study was to investigate the allelopathic potential of P. arachnoideum by isolating and identifying any secondary metabolites with phytotoxic activity in its tissues, litter, and soil. Bioguided phytochemical investigation led to the isolation and identification of the proanthocyanidin selligueain A as the major secondary compound in the green fronds and litter of this fern. It is produced by P. arachnoideum in its green fronds, remains unaltered during the senescence process, and is the major secondary compound present in litter. Selligueain A showed phytotoxic activity against the selected target species sesame (Sesamum indicum) early development. In particular, the compound inhibited root and stem growth, and root metaxylem cell size but did not affect chlorophyll content. This compound can be considered as an allelochemical because it is present in the soil under P. arachnoideum patches as one of the major compounds in the soil solution. This is the first report of the presence of selligueain A in any member of the Dennstaedtiaceae family and the first time an isolated and identified allelochemical produced by members of the Pteridium species complex has been described. This evidence of selligueain A as a putative allelochemical of P. arachnoideum reinforces the role of allelopathy in the dominance processes of this plant in the areas where it occurs. PMID- 27552162 TI - Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. AB - BACKGROUND: Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. This review was first published in 2011 and updated in January 2016. OBJECTIVES: We assessed the benefits and harms of thromboelastography (TEG)-guided or thromboelastometry (ROTEM)-guided transfusion in adults and children with bleeding. We looked at various outcomes, such as overall mortality and bleeding events, conducted subgroup and sensitivity analyses, examined the role of bias, and applied trial sequential analyses (TSAs) to examine the amount of evidence gathered so far. SEARCH METHODS: In this updated review we identified randomized controlled trials (RCTs) from the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE; Embase; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 5 January 2016). We contacted trial authors, authors of previous reviews, and manufacturers in the field. The original search was run in October 2010. SELECTION CRITERIA: We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement, guided by standard laboratory tests, or a combination. We also included interventional algorithms including both TEG or ROTEM in combination with standard laboratory tests or other devices. The primary analysis included trials on TEG or ROTEM versus any comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data; we resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CIs). Due to skewed data, meta-analysis was not provided for continuous outcome data. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect based on the presence of coagulopathy of a TEG- or ROTEM-guided algorithm, and in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through TSA. MAIN RESULTS: We included eight new studies (617 participants) in this updated review. In total we included 17 studies (1493 participants). A total of 15 trials provided data for the meta-analyses. We judged only two trials as low risk of bias. The majority of studies included participants undergoing cardiac surgery.We found six ongoing trials but were unable to retrieve any data from them. Compared with transfusion guided by any method, TEG or ROTEM seemed to reduce overall mortality (7.4% versus 3.9%; risk ratio (RR) 0.52, 95% CI 0.28 to 0.95; I(2) = 0%, 8 studies, 717 participants, low quality of evidence) but only eight trials provided data on mortality, and two were zero event trials. Our analyses demonstrated a statistically significant effect of TEG or ROTEM compared to any comparison on the proportion of participants transfused with pooled red blood cells (PRBCs) (RR 0.86, 95% CI 0.79 to 0.94; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), fresh frozen plasma (FFP) (RR 0.57, 95% CI 0.33 to 0.96; I(2) = 86%, 8 studies, 761 participants, low quality of evidence), platelets (RR 0.73, 95% CI 0.60 to 0.88; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), and overall haemostatic transfusion with FFP or platelets (low quality of evidence). Meta-analyses also showed fewer participants with dialysis-dependent renal failure.We found no difference in the proportion needing surgical reinterventions (RR 0.75, 95% CI 0.50 to 1.10; I(2) = 0%, 9 studies, 887 participants, low quality of evidence) and excessive bleeding events or massive transfusion (RR 0.38, 95% CI 0.38 to 1.77; I(2) = 34%, 2 studies, 280 participants, low quality of evidence). The planned subgroup analyses failed to show any significant differences.We graded the quality of evidence as low based on the high risk of bias in the studies, large heterogeneity, low number of events, imprecision, and indirectness. TSA indicates that only 54% of required information size has been reached so far in regards to mortality, while there may be evidence of benefit for transfusion outcomes. Overall, evaluated outcomes were consistent with a benefit in favour of a TEG- or ROTEM-guided transfusion in bleeding patients. AUTHORS' CONCLUSIONS: There is growing evidence that application of TEG- or ROTEM-guided transfusion strategies may reduce the need for blood products, and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG- or ROTEM-guided transfusion in acute settings and other patient categories in low risk of bias studies is needed. PMID- 27552163 TI - Evaluation of AMGEN clone 9G8A anti-Epo antibody for application in doping control. AB - The two mouse monoclonal anti-erythropoietin (EPO) antibodies clone AE7A5 (generated by using a 26 amino acid N-terminal EPO-peptide) and 9G8A (developed by immunizing mice with full length human EPO) are both directed against linear epitopes at the N-terminus of EPO. While AE7A5 has been commercially available for many years, 9G8A was made for Amgen's internal research purposes. In the past, the commercial antibody was shown to cross-react with several proteins unrelated to EPO (e.g. E. coli thioredoxin reductase, zinc-alpha2-glycoprotein, S. cerevisiae enolase, human neuron-specific enolase, and human non-neuronal enolase). However, it displayed high sensitivity for detecting recombinant EPO (rEPO) misuse by athletes on Western blots. We evaluated the potential use of clone 9G8A for doping control purposes. While 9G8A showed lower sensitivity than AE7A5 (ca 45% on isoelectric focusing (IEF)-polyacrylamide gel electrophoresis (PAGE), ca 40% on sodium dodecyl sulfate (SDS)- and sarcosyl (SAR)-PAGE), non specific binding of the five proteins was not observed. The cross-reactivity of AE7A5 can be overcome by immunoaffinity purification of EPO before electrophoresis and Western blotting. Similar to AE7A5, clone 9G8A is also suited for Western double-blotting. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27552164 TI - Immunomagnetic separation combined with colony immunoblotting for selective enrichment and detection of piliated Lactobacillus rhamnosus strains. AB - AIMS: Piliated Lactobacillus rhamnosus (pLR) strains have attracted much attention owing to their excellent mucus adhering capacity and immunomodulatory effects. Here, we aimed to develop a rapid, sensitive method for isolating pLR strains in complex ecosystems using immunomagnetic separation (IMS) with colony immunoblotting (CIB). METHODS AND RESULTS: Magnetic nanobeads (diameter: 180 nm) conjugated with anti-pLR SpaA pilin antibodies (anti-SpaA) were prepared and used to preconcentrate pLR strains in samples, followed by confirmation with anti-SpaA based CIB analysis. Under optimized experimental conditions, IMS-CIB selectively recovered pLR strains from 107 CFU ml-1 of faecal microbiota samples spiked with 2.9 * 101 to 2.4 * 106 CFU ml-1 of pLR strains. No positive colonies were detected in samples without addition of pLR strains. The detection limit of IMS CIB was 29 CFU pLR ml-1 of faecal microbiota, which is much lower than that of CIB without IMS preconcentration (2.0 * 104 CFU ml-1 ). CONCLUSIONS: IMS-CIB allowed selective preconcentration of pLR strains in highly heterogeneous bacterial suspensions and direct detection of pLR colonies, which remained readily available for subsequent isolation. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings established an effective method for selective enrichment and detection of pLR strains. PMID- 27552165 TI - Degradation of Kidney and Psoas Muscle Proteins as Indicators of Post-Mortem Interval in a Rat Model, with Use of Lateral Flow Technology. AB - We investigated potential protein markers of post-mortem interval (PMI) using rat kidney and psoas muscle. Tissue samples were taken at 12 h intervals for up to 96 h after death by suffocation. Expression levels of eight soluble proteins were analyzed by Western blotting. Degradation patterns of selected proteins were clearly divided into three groups: short-term, mid-term, and long-term PMI markers based on the half maximum intensity of intact protein expression. In kidney, glycogen synthase (GS) and glycogen synthase kinase-3beta were degraded completely within 48 h making them short-term PMI markers. AMP-activated protein kinase alpha, caspase 3 and GS were short-term PMI markers in psoas muscle. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was a mid-term PMI marker in both tissues. Expression levels of the typical long-term PMI markers, p53 and beta-catenin, were constant for at least 96 h post-mortem in both tissues. The degradation patterns of GS and caspase-3 were verified by immunohistochemistry in both tissues. GAPDH was chosen as a test PMI protein to perform a lateral flow assay (LFA). The presence of recombinant GAPDH was clearly detected in LFA and quantified in a concentration-dependent manner. These results suggest that LFA might be used to estimate PMI at a crime scene. PMID- 27552166 TI - Women with Visual Impairment and Insured by Medicaid or Medicare Are Less Likely to Receive Recommended Screening for Breast and Cervical Cancers. AB - PURPOSE: To investigate whether women with visual impairment (VI) receive mammography and Pap testing to the same extent as women without VI among the low income population or those aged 65+ years. METHODS: We analyzed the 2000-2010 Medicaid and Medicare data for South Carolina women. Women with VI were identified on the basis of a qualifying diagnosis in billing data. We assessed women's adherence (full adherence, partial adherence and no screening) with two United States Preventive Services Task Force (USPSTF) cancer screening recommendations (mammography and Pap testing) throughout the course of the study period. Multinomial models were estimated to describe the association between VI and adherence to the two cancer screening recommendations. RESULTS: A total of 1308 women with VI and 2635 women without VI (mammography) and 1247 women with VI and 2483 women without VI (Pap testing) were included in the study. After adjusting for age, number of eligible enrollment years, insurance type (Medicare, Medicaid, or both), urban or rural residence and having a hysterectomy, women with VI were significantly less likely than those without VI to have full adherence to mammography recommendations (adjusted odds ratio, OR, 0.49, 95% confidence interval, CI, 0.40-0.60) and Pap testing recommendations (adjusted OR 0.32, 95% CI 0.27-0.39). CONCLUSION: We used a new approach to investigate adherence to USPSTF recommendations, accounting for both full and partial adherence. This approach identified disparities in mammography and Pap testing for women with VI. The findings of this study should facilitate the development of effective interventions to increase screening among women with VI. PMID- 27552167 TI - A new finding of a tethered cord in a patient with Okamoto syndrome. PMID- 27552168 TI - Should we SUSPEND MET? Not really. PMID- 27552169 TI - Modulation of Conformational Equilibria in the S-Adenosylmethionine (SAM) II Riboswitch by SAM, Mg(2+), and Trimethylamine N-Oxide. AB - The dependence of the conformation of the S-adenosylmethionine (SAM) II riboswitch on the concentration of added Mg(2+) ions and SAM, individually and in mixtures, was monitored by circular dichroism (CD) spectroscopy and by measurement of the diffusion coefficient. The results are analyzed in the context of two complementary quantitative models, both of which are consistent with a single underlying physical model. Magnesium binding sites in the open state have an affinity on average higher than the affinity of those in the compact state, but formation of the compact state is accompanied by an increase in the number of binding sites. Consequently, at low Mg(2+) concentrations, Mg(2+) binds preferentially to the open state, favoring its formation, but at high concentrations, Mg(2+) binds preferentially to the compact state. The affinity of the riboswitch for SAM increases drastically with an increased level of binding of Mg(2+) to the compact pseudoknot conformation. The effect of increasing concentrations of trimethylamine N-oxide (TMAO), a well-studied molecular crowding agent, on the conformation of the riboswitch and its affinity for SAM were also monitored by CD spectroscopy and measurement of diffusion. In the absence of added Mg(2+), high concentrations of TMAO were found to induce a conformational change compatible with the formation of the pseudoknot form but have only a small effect on the affinity of the RNA for SAM. PMID- 27552170 TI - Handover and transport of critically ill children: An integrative review. AB - BACKGROUND: The handover and transport of critically ill pediatric patients requires communication amongst multiple disciplines. Poor communication is a leading cause of sentinel events and human factors affect handover and transport. OBJECTIVES: To synthesize published data on pediatric handover and transport and identify gaps to provide direction for future investigation. METHODS: Integrative literature review. RESULTS: Forty research studies were reviewed and revealed the following themes: risk for patient complications, standardized communication, and specialized teams and teamwork were associated with improved outcomes. No articles were identified regarding transportation of critically ill pediatric patients from the emergency room to the intensive care unit. There was a knowledge gap in best practices in handover and transport within the unique subsets of the pediatric population including neonate, toddler, school-aged, and adolescents. CONCLUSIONS: Research supported a combined approach of specialized teams using standardized communication in the handover and transport of the pediatric patient to improve outcomes. Further study is warranted on interprofessional (team to team) handover practices, select subsets of the pediatric population, and the handover and transport of critically ill patients from the emergency room to the intensive care unit. PMID- 27552171 TI - Effect of XiangBin granules on post-operative gastrointestinal function and brain gut peptides after transabdominal gynecological surgery. AB - OBJECTIVES: We conducted a prospective clinical randomized single-blind placebo controlled trial (ChiCTR-TRC-14004156) to observe the effect of XiangBin granules on the recovery of gastrointestinal function and levels of brain-gut peptide motilin (MTL); vasoactive intestinal peptide (VIP); growth hormone releasing peptide-ghrelin, GHRP-ghrelin, and corticotropin releasing hormone (CRH), after transabdominal gynecological surgery. STUDY DESIGN: Patients undergoing gynecologic abdominal surgery were randomly divided in a 2:1 ratio (according to the data of pre-trial which was a small sample randomized trial in gynecology inpatient) into two groups: the larger treatment group taking XiangBin granules, and the smaller placebo group taking Chinese herbal placebo. The aim was to observe anal exhaust time, time to defecation, and the change in level of brain gut peptide. RESULT: A significantly shorter time to first postoperative anal exhaust was observed in the treatment group. In the placebo group, the MTL level on the first day after surgery was lower than the preoperative level (P<0.05). In both groups, the GHRP-ghrelin level on the first postoperative day was lower than the preoperative level (P<0.05). In the treatment group, the GHRP-ghrelin level of the third day after surgery was higher than the first day after surgery (P<0.05). The CRH level on the first postoperative day was lower in the treatment group compared to the placebo group (P<0.05). CONCLUSION: XiangBin granules can effectively promote the recovery of gastrointestinal function after surgery for gynecologic abdomen and promote GHRP-ghrelin and MTL recovery, and reduce the postoperative secretion of CRH. PMID- 27552172 TI - Uterus transplantation in France: for which patients? AB - OBJECTIVE: Uterine infertility (UI), which can be caused by a variety of congenital or acquired factors, affects several thousand women in Europe. Uterus transplantation (UTx), at the current stage of research, offers hope for these women to be both the biological mother and the carrier of their child. However, the indications of UTx still need to be defined. The main aim of the study was to describe the different etiologies of UI and other data as marital and parental status from women requesting UTx who contacted us in the framework of a UTx clinical trial. Secondarily, we discussed the potential indications of UTx and their feasibility. STUDY DESIGN: This is an observational study. RESULTS: Of a total of 139 patients with UI, 105 patients (75.5%) had uterine agenesis, making it the leading cause of UI in this sample. Among the patients with uterine agenesis, 25% had a solitary kidney and 44.7% had undergone vaginal reconstruction. Peripartum hysterectomy, hysterectomy for cancer, and hysterectomy for benign pathologies accounted for 9.4%, 7.2% and 5% of cases, respectively. Less common causes of UI included complete androgen insensitivity syndrome (2.2% of patients) and prenatal diethylstilbestrol exposure (0.7%). Approximately 14% of the women already had at least one child and 66% were in a couple living together for at least 2 years. CONCLUSION: UTx is still under evaluation and further research is under way. Nulliparous patients with no major medical or surgical history and with normal ovarian function, who meet the legal criteria for medically assisted reproduction, represent the best indications for UTx at this stage of its development. PMID- 27552173 TI - The effect of prenatally administered vaginal progesterone on uterine artery Doppler in asymptomatic twin pregnancies. AB - OBJECTIVES: This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations. STUDY DESIGN: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization. RESULTS: The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation. CONCLUSIONS: In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation. PMID- 27552174 TI - Lack of information received by a French female cohort regarding prevention against exposure to reprotoxic agents during pregnancy. AB - OBJECTIVE: The aim of this study was to evaluate the information pregnant women received regarding possible exposures to five recognized reprotoxic agents during their pregnancy. STUDY DESIGN: A cohort study was conducted using two postnatal units in France. Women hospitalized in postnatal units were requested to complete a self-administered two part questionnaire. The first part gathered information about the patient's socio-professional level and the type of pregnancy follow-up. The second part examined the information the patient received regarding daily products containing the following known reprotoxic agents: bisphenol A, toluene, n-hexane, cis-chloroallyl-triaza-azonia-adamantane-chloride and O-phenyl-phenol. The women cited the sources of information. We combined the employment status and educational level to separate the women into two groups. The groups were then compared using the Chi Square test or Fisher's exact test. RESULT(S): There were 390 women in this study. Our results showed the women received information regarding the following: 21.6% (n=84) regarding tin cans, 21.9% (n=85) concerning plastic meal boxes when heated in microwave ovens, 8.8% (n=32) about water in gas bottles, 27.4% (n=106) about non-organic foods, 39.3% (n=152) about hair dyes, 17% (n=66) about nail polishes, 23.4% (n=103) about insect repellents, 34.4% (n=133) about "do-it-yourself" products, 2.1% (n=8) about gardening products, 26.7% (n=103) about electric plug-in repellents, 21.1% (n=81) about housekeeping products, and 6.8% (n=26) about register receipts. Women with a higher level of education and a qualified occupation were better informed about these daily products. These women were more likely to learn the information on their own (internet, media). CONCLUSION(S): Our study showed French women did not receive sufficient information regarding potential exposures to reprotoxic agents during pregnancy. PMID- 27552175 TI - Graphene-Elastomer Composites with Segregated Nanostructured Network for Liquid and Strain Sensing Application. AB - One of the critical issues for the fabrication of desirable sensing materials has focused on the construction of an effective continuous network with a low percolation threshold. Herein, graphene-based elastomer composites with a segregated nanostructured graphene network were prepared by a novel and effective ice-templating strategy. The segregated graphene network bestowed on the natural rubber (NR) composites an ultralow electrical percolation threshold (0.4 vol %), 8-fold lower than that of the NR/graphene composites with homogeneous dispersion morphology (3.6 vol %). The resulting composites containing 0.63 vol % graphene exhibited high liquid sensing responsivity (6700), low response time (114 s), and good reproducibility. The unique segregated structure also provides this graphene based elastomer (containing 0.42 vol % graphene) with exceptionally high stretchability, sensitivity (gauge factor ~ 139), and good reproducibility (~400 cycles) of up to 60% strain under cyclic tests. The fascinating performances highlight the potential applications of graphene-elastomer composites with an effective segregated network as multifunctional sensing materials. PMID- 27552176 TI - Chronic Daily Headache: Ten Steps for Primary Care Providers to Regain Control. AB - BACKGROUND: Chronic daily headache (CDH) affects 2% to 4% of the North American and European population. Various pathways lead to this condition, although chronification of migraine and the occurrence of central sensitization in tension headache are the 2 most common. Medication overuse headaches complicate a substantial portion of other primary headaches that have become chronic and often make their treatment more complex and less successful. METHODS/RESULTS: A 10-step process to help primary care providers evaluate and treat CDH patients begins with excluding secondary headache disorders, then moves on to classification of the primary underlying headache disorder. Next, the exacerbating factors, as well as relevant comorbid conditions, are identified. The patient's current acute therapy is examined, and attempts are made to identify and resolve medication overuse if present. Past preventive therapies are reviewed, allowing for thoughtful design of a headache action plan with preventive, acute, and lifestyle components. Patients are asked to keep a headache diary, used to initiate a cycle of continuous improvement in a patient's response to acute and preventive therapeutic approaches. CONCLUSIONS: A systematic approach and partnership with patients often make it possible to convert CDH to episodic headache that is responsive to both acute and preventive therapies. PMID- 27552177 TI - Preharvest UV-C radiation influences physiological, biochemical, and transcriptional changes in strawberry cv. Camarosa. AB - Ultraviolet C (UV-C) radiation is known for preventing fungal decay and enhancing phytochemical content in fruit when applied postharvest. However, limited knowledge is available regarding fruit responses to preharvest application of UV C radiation. Thus, the effects of UV-C radiation on photosynthetic efficiency, dry matter accumulation and partitioning, fruit yield and decay, phytochemical content, and relative transcript accumulation of genes associated with these metabolic pathways were monitored in strawberry (Fragaria x ananassa Duch.) cv. Camarosa. A reduction in photosynthetic efficiency was followed by a decrease in light harvesting complex LhcIIb-1 mRNA accumulation as well as a decrease in yield per plant. Phenylalanine ammonia lyase activity, phenolic, anthocyanin, and L-ascorbic acid contents were higher in UV-C treated fruit. In addition, preharvest UV-C treatment reduced microorganism incidence in the greenhouse and on the fruit surface, increased the accumulation of beta-1,3-Gluc and PR-1 mRNA, and prevented fruit decay. PMID- 27552178 TI - Implications of leaf ontogeny on drought-induced gradients of CAM expression and ABA levels in rosettes of the epiphytic tank bromeliad Guzmania monostachia. AB - Guzmania monostachia is an epiphytic heteroblastic bromeliad that exhibits rosette leaves forming water-holding tanks at maturity. Different portions along its leaf blades can display variable degrees of crassulacean acid metabolism (CAM) up-regulation under drought. Since abscisic acid (ABA) can act as an important long-distance signal, we conducted a joint investigation of ontogenetic and drought impacts on CAM intensity and ABA levels in different leaf groups within the G. monostachia rosette. For this, three groups of leaves were analysed according to their position within the mature-tank rosette (i.e., younger, intermediate, and older leaves) to characterize the general growth patterns and magnitude of drought-modulated CAM expression. CAM activity was evaluated by analysing key molecules in the biochemical machinery of this photosynthetic pathway, while endogenous ABA content was comparatively measured in different portions of each leaf group after seven days under well-watered (control) or drought treatment. The results revealed that G. monostachia shows more uniform morphological characteristics along the leaves when in the atmospheric stage. The drought treatment of mature-tank rosettes generally induced in older leaves a more severe water loss, followed by the lowest CAM activity and a higher increase in ABA levels, while younger leaves showed an opposite response. Therefore, leaf groups at distinct ontogenetic stages within the tank rosette of G. monostachia responded to drought with variable degrees of water loss and CAM expression. ABA seems to participate in this tissue-compartmented response as a long-distance signalling molecule, transmitting the drought-induced signals originated in older leaves towards the younger ones. PMID- 27552179 TI - Carotenoid profiling, in silico analysis and transcript profiling of miRNAs targeting carotenoid biosynthetic pathway genes in different developmental tissues of tomato. AB - Carotenoid biosynthetic pathway is one of the highly significant and very well elucidated secondary metabolic pathways in plants. microRNAs are the potential regulators, widely known for playing a pivotal role in the regulation of various biological as well as metabolic processes. miRNAs may assist in the metabolic engineering of the secondary metabolites for the production of elite genotypes with increased biomass and content of various metabolites. miRNA mediated regulation of carotenoid biosynthetic genes has not been elucidated so far. To illustrate the potential regulatory role of miRNAs in carotenoid biosynthesis, transcript profiling of the known miRNAs and their possible target carotenoid genes was undertaken at eight different developmental stages of tomato, using stem-loop PCR approach combined with quantitative RT-PCR. The inter-relationship amongst carotenoid content, biosynthetic genes and miRNAs was studied in depth. Comparative expression profiles of miRNA and target genes showed variable expression in different tissues studied. The expression level of miRNAs and their target carotenoid genes displayed similar pattern in the vegetative tissues as compared to the reproductive ones, viz. fruit (different stages), indicating the possibility of regulation of carotenoid biosynthesis at various stages of fruit development. This was later confirmed by the HPLC analysis of the carotenoids. The present study has further enhanced the understanding of regulation of carotenoid biosynthetic pathway in plants. The identified miRNAs can be employed to manipulate the biosynthesis of different carotenoids, through metabolic engineering for the production of lycopene rich tomatoes. PMID- 27552180 TI - Differential expression of two galactinol synthase isoforms LcGolS1 and LcGolS2 in developing lentil (Lens culinaris Medik. cv CDC Redberry) seeds. AB - Galactinol synthase (GS, EC 2.4.1.123) catalyzes the transfer of a galactosyl residue from UDP-galactose to myo-inositol to synthesize galactinol, a precursor for raffinose family oligosaccharides (RFO) biosynthesis. Screening, a cDNA library constructed with RNA isolated from developing lentil seeds, with partial GS genes resulted in identification of cDNA clones for two isoforms of GS, LcGolS1 (1336 bp, ORF-1002 bp, 334 amino acids) and LcGolS2 (1324bp, ORF-975bp, 325 amino acids) with predicted molecular weights of 38.7 kDa and 37.6 kDa, respectively. During lentil seed development, LcGolS1 transcripts showed higher accumulation during 26-32 days after flowering (DAF) corresponding to seed desiccation, while LcGolS2 showed maximum accumulation at 24 DAF, prior to increase in LcGolS1 transcripts. GS enzyme activity was maximum at 26 and 28 DAF and corresponded to galactinol accumulation, which also increased rapidly at 22 DAF with maximum accumulation at 26 DAF. Substrates for GS activity, myo-inositol and glucose/galactose were present in high concentrations during early stages of seed development but gradually decreased from 20 DAF to 32 DAF when galactinol concentration increased coinciding with increased GS enzyme activity. PMID- 27552181 TI - Untargeted Identification of Wood Type-Specific Markers in Particulate Matter from Wood Combustion. AB - Residential wood combustion emissions are one of the major global sources of particulate and gaseous organic pollutants. However, the detailed chemical compositions of these emissions are poorly characterized due to their highly complex molecular compositions, nonideal combustion conditions, and sample preparation steps. In this study, the particulate organic emissions from a masonry heater using three types of wood logs, namely, beech, birch, and spruce, were chemically characterized using thermal desorption in situ derivatization coupled to a GCxGC-ToF/MS system. Untargeted data analyses were performed using the comprehensive measurements. Univariate and multivariate chemometric tools, such as analysis of variance (ANOVA), principal component analysis (PCA), and ANOVA simultaneous component analysis (ASCA), were used to reduce the data to highly significant and wood type-specific features. This study reveals substances not previously considered in the literature as meaningful markers for differentiation among wood types. PMID- 27552182 TI - Label-Free Photonic Crystal-Based beta-Lactamase Biosensor for beta-Lactam Antibiotic and beta-Lactamase Inhibitor. AB - A simple, label-free, and visual photonic crystal-based beta-lactamase biosensor was developed for beta-lactam antibiotic and beta-lactamase inhibitor in which the penicillinase (a beta-lactamase) was immobilized on the pH-sensitive colloidal crystal hydrogel (CCH) film to form penicillinase colloidal crystal hydrogel (PCCH) biosensing film. The hydrolysis of penicillin G (a beta-lactam antibiotic) can be catalyzed by penicillinase to produce penicilloic acid, leading to a pH decrease in the microenvironment of PCCH film, which causes the shrink of pH-sensitive CCH film and triggers a blue-shift of the diffraction wavelength. Upon the addition of beta-lactamase inhibitor, the hydrolysis reaction is suppressed and no clear blue-shift is observed. The concentrations of beta-lactam antibiotic and beta-lactamase inhibitor can be sensitively evaluated by measuring the diffraction shifts. The minimum detectable concentrations for penicillin G and clavulanate potassium (a beta-lactamase inhibitor) can reach 1 and 0.1 MUM, respectively. Furthermore, the proposed method is highly reversible and selective, and it allows determination of penicillin G in fish pond water samples. PMID- 27552183 TI - Photophysical Properties of Fluorescent Core Dendrimers Controlled by Size. AB - A series of different generation PAMAM dendrimers with sulforhodamine B covalently attached to the dendrimer core was investigated regarding their optical properties. Steady-state and time-resolved spectroscopic techniques were used to determine the size influence of the dendrimers on the photophysical behavior of the luminescent core. New blue emissive species were formed as the generation increased from zero to four. The growth of the dendritic branches resulted in a rise of fluorescence quantum yield and fluorescence lifetime values. Rotational correlation times were used to determine the hydrodynamic diameters of the fluorescent-core dendrimers, and good accordance was found with the values previously reported for unlabeled PAMAM dendrimers, which makes them potentially suitable diagnostic tools for biomedical tracing. PMID- 27552184 TI - Targeted re-sequencing confirms the importance of chemosensory genes in aphid host race differentiation. AB - Host-associated races of phytophagous insects provide a model for understanding how adaptation to a new environment can lead to reproductive isolation and speciation, ultimately enabling us to connect barriers to gene flow to adaptive causes of divergence. The pea aphid (Acyrthosiphon pisum) comprises host races specializing on legume species and provides a unique system for examining the early stages of diversification along a gradient of genetic and associated adaptive divergence. As host choice produces assortative mating, understanding the underlying mechanisms of choice will contribute directly to understanding of speciation. As host choice in the pea aphid is likely mediated by smell and taste, we use capture sequencing and SNP genotyping to test for the role of chemosensory genes in the divergence between eight host plant species across the continuum of differentiation and sampled at multiple locations across western Europe. We show high differentiation of chemosensory loci relative to control loci in a broad set of pea aphid races and localities, using a model-free approach based on principal component analysis. Olfactory and gustatory receptors form the majority of highly differentiated genes and include loci that were already identified as outliers in a previous study focusing on the three most closely related host races. Consistent indications that chemosensory genes may be good candidates for local adaptation and barriers to gene flow in the pea aphid open the way to further investigations aiming to understand their impact on gene flow and to determine their precise functions in response to host plant metabolites. PMID- 27552185 TI - Can Better Emotion Regulation Protect against Suicidality in Traumatized Homeless Youth? AB - A substantial majority of homeless youth and young adults (HYA) experience abuse prior to and during homelessness. HYA also have high rates of posttraumatic stress disorder (PTSD) and suicidal behavior. This study investigated relationships between traumatic experiences, PTSD symptoms, substance use, and the protective effects of emotion regulation on outcome variables suicidal ideation and suicide attempts. Data were drawn from a sample of 398 HYA interviewed at 3 drop-in centers in Los Angeles County. A bivariate logistic regression modeling strategy was employed to examine relationships among demographic characteristics and dependent and independent variables. Trauma prior to homelessness and trauma prior to and after homelessness were positively associated with suicidal ideation, whereas emotional awareness and control demonstrated negative associations. PTSD symptoms were positively associated with suicide attempts, whereas emotional awareness and control demonstrated negative associations. Better emotion regulation is associated with reduced odds of suicidal ideation and attempts in HYA and may protect against effects of traumatic experiences. Interventions targeting emotion regulation skills in HYA to reduce suicidality associated with traumatic experiences merit additional investigation. PMID- 27552186 TI - 1alpha,25-Dihydroxyvitamin D Inhibits the Metastatic Capability of MCF10CA1a and MDA-MB-231 Cells in an In Vitro Model of Breast to Bone Metastasis. AB - Breast cancer metastasis to the bone continues to be a major health problem, with approximately 80% of advanced breast cancer patients expected to develop bone metastasis. Although the problem of bone metastasis persists, current treatment options for metastatic cancer patients are limited. In this study, we investigated the preventive role of the active vitamin D metabolite, 1alpha,25 dihydroxyvitamin D (1,25(OH)2D), against the metastatic potential of breast cancer cells using a novel three-dimensional model (rMET) recapitulating multiple steps of the bone metastatic process. Treatment of MCF10CA1a and MDA-MB-231 cells inhibited metastasis in the rMET model by 70% (+/-5.7%) and 21% (+/-6%), respectively. In addition, 1,25(OH)2D treatment decreased invasiveness (20 +/- 11% of vehicle) and decreased the capability of MCF10CA1a cells to survive in the reconstructed bone environment after successful invasion through the basement membrane (69 +/- 5% of vehicle). An essential step in metastasis is epithelial mesenchymal transition (EMT). Treatment of MCF10CA1a cells with 1,25(OH)2D increased gene (2.04 +/- 0.28-fold increase) and protein (1.87 +/- 0.20-fold increase) expression of E-cadherin. Additionally, 1,25(OH)2D treatment decreased N-cadherin gene expression (42 +/- 8% decrease), a marker for EMT. Collectively, the present study suggests that 1,25(OH)2D inhibits breast cancer cell metastatic capability as well as inhibits EMT, an essential step in the metastatic process. PMID- 27552187 TI - Alloyed 2D Metal-Semiconductor Heterojunctions: Origin of Interface States Reduction and Schottky Barrier Lowering. AB - The long-term stability and superior device reliability through the use of delicately designed metal contacts with two-dimensional (2D) atomic-scale semiconductors are considered one of the critical issues related to practical 2D based electronic components. Here, we investigate the origin of the improved contact properties of alloyed 2D metal-semiconductor heterojunctions. 2D WSe2 based transistors with mixed transition layers containing van der Waals (M-vdW, NbSe2/WxNb1-xSe2/WSe2) junctions realize atomically sharp interfaces, exhibiting long hot-carrier lifetimes of approximately 75,296 s (78 times longer than that of metal-semiconductor, Pd/WSe2 junctions). Such dramatic lifetime enhancement in M-vdW-junctioned devices is attributed to the synergistic effects arising from the significant reduction in the number of defects and the Schottky barrier lowering at the interface. Formation of a controllable mixed-composition alloyed layer on the 2D active channel would be a breakthrough approach to maximize the electrical reliability of 2D nanomaterial-based electronic applications. PMID- 27552188 TI - Response to Giovanni Battista Morgagni and the Foundation of Modem Medicine. PMID- 27552189 TI - Colloidal Assembly of Hierarchically Structured Porous Supraparticles from Flower Shaped Protein-Inorganic Hybrid Nanoparticles. AB - Mimicry of biomineralization is an attractive strategy to fabricate nanostructured hybrid materials. While biomineralization involves processes that organize hybrid clusters into complex structures with hierarchy, arrangement of artificial components in biomimetic approaches has been challenging. Here, we demonstrate self-assembly of hierarchically structured porous supraparticles from protein-inorganic hybrid flower-shaped (FS) nanoparticle building blocks. In our strategy, the FS nanoparticles self-assemble via high valency interactions in combination with interfacial adsorption and compression. The flower-like shape directed robust assembly of the FS nanoparticles into chain-like clusters in solution, which were further assembled into spherical supraparticles during rotation of FS nanoparticle solution. Continuously expanding and contracting the air-water interface during rotation catalyzed assembly of FS nanoparticle clusters, indicating that adsorption and compression of the building blocks at the interface were critical. The resulting supraparticles contain hierarchical pores which are translated from the structural characteristics of individual FS nanoparticle building blocks. The protein-inorganic supraparticles are protein compatible, have large surface area, and provide specific affinity recognition for robust protein immobilization. A variety of functional proteins could be immobilized to the porous supraparticles, making it a general platform that could provide benefits for many applications. PMID- 27552190 TI - Development and validation of an LC-MS/MS method for the determination of hinokiflavone in rat plasma and its application to a pharmacokinetic study. AB - Hinokiflavone has drawn a lot of attention for its multiple biological activities. In this study, a sensitive and selective method for determination of hinokiflavone in rat plasma was developed for the first time, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Amentoflavone was used as an internal standard. Separation was achieved on a Hypersil Gold C18 column with isocratic elution using methanol-water (65:35, v/v) as mobile phase at a flow rate of 0.3 mL/min. A triple quadrupole mass spectrometer operating in the negative electrospray mode with selected reaction monitoring was used to detect the transitions of m/z 537 -> 284 for hinokiflavone and m/z 537 -> 375 for IS. The LOQ was 0.9 ng/mL with a linear range of 0.9-1000 ng/mL. The intra- and inter day accuracy (RE%) ranged from -3.75 to 6.91% and from -9.20 to 2.51% and the intra- and inter-day precision (RSD) was between 0.32-14.11 and 2.85-10.04%. The validated assay was successfully applied to a pharmacokinetic study of hinokiflavone in rats. The half-life of drug elimination at the terminal phase was 6.10 +/- 1.86 h, and the area under the plasma concentration-time curve from time zero to the time of last measurable concentration and to infinity values obtained were 2394.42 +/- 466.86 and 2541.93 +/- 529.85 h ng/mL, respectively. PMID- 27552191 TI - Microscale Silicon Origami. AB - A new methodology to create 3D origami patterns out of Si nanomembranes using pre stretched and pre-patterned polydimethylsiloxane substrates is reported. It is shown this approach is able to mimic paper-based origami patterns. The combination of origami-based microscale 3D architectures and stretchable devices will lead to a breakthrough on reconfigurable systems. PMID- 27552192 TI - Thinking high but feeling low: An exploratory cluster analysis investigating how implicit and explicit spider fear co-vary. AB - Research has demonstrated large differences in the degree to which direct and indirect measures predict each other and variables including behavioural approach and attentional bias. We investigated whether individual differences in the co variance of "implicit" and "explicit" spider fear exist, and whether this covariation exerts an effect on spider fear-related outcomes. One hundred and thirty-two undergraduate students completed direct and indirect measures of spider fear/avoidance, self-report questionnaires of psychopathology, an attentional bias task, and a proxy Behavioural Approach Task. TwoStep cluster analysis using implicit and explicit spider fear as criterion variables resulted in three clusters: (1) low explicit/low implicit; (2) average explicit/high implicit; and (3) high explicit/low implicit. Clusters with higher explicit fear demonstrated greater disgust propensity and sensitivity and less willingness to approach a spider. No differences between clusters emerged on anticipatory approach anxiety or attentional bias. We discuss results in terms of dual-systems and cognitive-behavioural models of fear. PMID- 27552193 TI - Interactions between the Bumblebee Bombus pascuorum and Red Clover (Trifolium pratense) Are Mediated by Plant Genetic Background. AB - Wildflower mixes are often planted around field margins to provide forage for pollinators. Although seed for these mixtures is often wild-sourced, for species where agricultural cultivars are available, for example red clover (Trifolium pratense), cultivars can also be included. Previous evidence suggests that plant genetic background can have a strong influence on plant-arthropod interactions and therefore the provenance and genetic background of the plants included in wildflower mixes could impact plant-pollinator interactions. We tested the performance of five individual T. pratense cultivars against two commercially available wild-sourced T. pratense populations in terms of their ability to attract potential pollinator species (focusing on bumblebees) and their floral traits using greenhouse and garden experiments. The main bumblebee observed interacting with T. pratense was Bombus pascuorum and we found no difference in the absolute number of B. pascuorum visiting the cultivars or wild populations. However, we found variation among cultivars and between wild populations in their ability to attract bumblebees, which seems to be related to their relative investment in different floral traits. There was a positive relationship between biomass and number of inflorescences produced by the wild populations of T. pratense, which was not apparent for the cultivars. This suggests that artificial selection on the cultivars has changed the G-matrix of correlated traits. We show that agricultural cultivars of T. pratense can be as effective as wild populations at attracting pollinators such as bumblebees, but that the genetic background of both cultivars and wild populations can have a significant impact on the attractiveness of the plant to pollinators. We also show divergence in the correlated traits of T. pratense cultivars and wild populations that could lead to outbreeding depression if the plants interbreed. PMID- 27552194 TI - Factors associated with mobile health information seeking among Singaporean women. AB - This study examined effects of age and social psychological factors on women's willingness to be mobile health information seekers. A national survey of 1,878 Singaporean women was conducted to obtain information on women's mobile phone usage, experiences of health information seeking, and appraisals of using mobile phones to seek health information. Results showed that young, middle-aged, and older women exhibited distinct mobile phone usage behaviors, health information seeking patterns, and assessments of mobile health information seeking. Factors that accounted for their mobile information-seeking intention also varied. Data reported in this study provide insights into mobile health interventions in the future. PMID- 27552195 TI - The Effect of HIV and the Modifying Effect of Anti-Retroviral Therapy (ART) on Body Mass Index (BMI) and Blood Pressure Levels in Rural South Africa. AB - BACKGROUND: High BMI and blood pressure are leading chronic disease risk factors in South Africa. Longterm effects of HIV and ART on adiposity and blood pressure are poorly understood, and direct comparisons of risk factor trajectories in HIV- versus HIV+ populations are rare. METHODS: In 2003 and 2010, height, weight, and blood pressure were recorded in a study population (n = 505) in KwaZulu-Natal, South Africa (30% adult HIV prevalence). We modeled change in BMI and BP longitudinally in HIV- individuals (n = 315), seroconverters (n = 32), HIV+ patients not on ART (HIV+ART-; n = 52), HIV+ patients on ART for 0-<2 years as of 2010 (HIV+ART0-<2 yrs; n = 18), patients on ART for 2-5 years (HIV+ART2-5yrs; n = 44), and a subgroup with unknown HIV status (n = 44). Difference-in-differences were assessed in reference to the HIV- population. RESULTS: Between 2003 and 2010, BMI increased significantly in the HIV- group, by 0.874 (95% CI 0.339, 1.41; p = 0.001), to 30.4. BMI drop was significantly greater in HIV+ART0-<2yrs than in HIV+ART2-5yrs (p = 0.005). DID in BMI in HIV+ART0-<2yrs versus the reference was -5.21 (95% CI -7.53, -2.90; p = 0.001), and DID in HIV+ART2-5yrs versus reference was -1.35 (95% CI -2.89, 0.189; p = 0.086). DID in SBP in HIV+ART-vs HIV- DID was -7.55 mmHg (95% CI -13.2 to -1.90; p = 0.009). CONCLUSION: Short-term ART (0-<2 years) was associated with larger weight loss than either no ART or long-term ART. Once on ART for 2+ years, individuals 'caught up' on weight gain with the HIV- population. Our results showcase the importance of health system readiness to address the burgeoning double burden of disease in South Africa. PMID- 27552196 TI - Placoderm Assemblage from the Tetrapod-Bearing Locality of Strud (Belgium, Upper Famennian) Provides Evidence for a Fish Nursery. AB - The placoderm fauna of the upper Famennian tetrapod-bearing locality of Strud, Belgium, includes the antiarch Grossilepis rikiki, the arthrodire groenlandaspidid Turrisaspis strudensis and the phyllolepidid Phyllolepis undulata. Based on morphological and morphometric evidence, the placoderm specimens from Strud are predominantly recognised as immature specimens and this locality as representing a placoderm nursery. The Strud depositional environment corresponds to a channel in an alluvial plain, and the presence of a nursery in such environment could have provided nutrients and protection to the placoderm offspring. This represents one of the earliest pieces of evidence for this sort of habitat partitioning in vertebrate history, with adults living more distantly from the nursery and using the nursery only to spawn or give live birth. PMID- 27552198 TI - Presentations at the annual meeting of the Finnish Society for Rheumatology, Helsinki, 28-29 January 2016. PMID- 27552197 TI - Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways. AB - BACKGROUND: Interleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source. METHODS: Bronchial biopsies from 114 patients with mild-to moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17. RESULTS: In non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17-0.35) and eosinophils (B: 0.18, 95% CI: 0.07-0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining. CONCLUSIONS: We show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17. PMID- 27552200 TI - Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults. AB - PURPOSE: The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. METHOD: Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold. RESULTS: ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p < .0001, etap2 = .45). Adults had significantly larger wave V amplitudes to air- (p < .0001, etap2 = .50) and bone-conducted (p = .013, etap2 = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p < .0001, etap2 = .49) only with air-conducted CE-chirps. CONCLUSION: The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea. PMID- 27552201 TI - Developing metacognition through effective feedback. PMID- 27552202 TI - Molecular monitoring of chronic myeloid leukemia: present and future. AB - INTRODUCTION: Fusion of BCR-ABL1 genes causes chronic myeloid leukemia (CML). As a reliable marker of disease burden, it also serves as the target of tyrosine kinase inhibitors (TKIs). New more sensitive molecular diagnostic tools for BCR ABL1 can contribute to therapeutic decision-making, especially in considering drug discontinuation for patients enjoying prolonged deep molecular response. Areas covered: Several novel platforms are transforming CML molecular diagnostics to enable faster point-of-care devices, better understanding of clonal diversity and resistance mutations. Here, we review these molecular platforms, knowing implementation in other hematological malignancies will ensue. Expert commentary: Treatment with TKI in CML is the first example of a highly effective targeted therapy. Monitoring of BCR-ABL1 mRNA is standard in assessing disease burden being highly predictive of outcomes recommended by both European LeukemiaNet (ELN) and National Comprehensive Cancer Network (NCCN); however, studies has demonstrated poor adherence to these recommendations. In both clinical practice and assay performance, further optimizing of BCR-ABL1 monitoring can be envisioned including point-of-care methods for increased availability of rapid, standardized testing and increasingly sensitive molecular assays that allow for quantification of MRD and detecting resistance mutations. PMID- 27552203 TI - Performance Evaluation of Missing-Value Imputation Clustering Based on a Multivariate Gaussian Mixture Model. AB - BACKGROUND: It is challenging to deal with mixture models when missing values occur in clustering datasets. METHODS AND RESULTS: We propose a dynamic clustering algorithm based on a multivariate Gaussian mixture model that efficiently imputes missing values to generate a "pseudo-complete" dataset. Parameters from different clusters and missing values are estimated according to the maximum likelihood implemented with an expectation-maximization algorithm, and multivariate individuals are clustered with Bayesian posterior probability. A simulation showed that our proposed method has a fast convergence speed and it accurately estimates missing values. Our proposed algorithm was further validated with Fisher's Iris dataset, the Yeast Cell-cycle Gene-expression dataset, and the CIFAR-10 images dataset. The results indicate that our algorithm offers highly accurate clustering, comparable to that using a complete dataset without missing values. Furthermore, our algorithm resulted in a lower misjudgment rate than both clustering algorithms with missing data deleted and with missing-value imputation by mean replacement. CONCLUSION: We demonstrate that our missing-value imputation clustering algorithm is feasible and superior to both of these other clustering algorithms in certain situations. PMID- 27552205 TI - Physical applications of GPS geodesy: a review. AB - Geodesy, the oldest science, has become an important discipline in the geosciences, in large part by enhancing Global Positioning System (GPS) capabilities over the last 35 years well beyond the satellite constellation's original design. The ability of GPS geodesy to estimate 3D positions with millimeter-level precision with respect to a global terrestrial reference frame has contributed to significant advances in geophysics, seismology, atmospheric science, hydrology, and natural hazard science. Monitoring the changes in the positions or trajectories of GPS instruments on the Earth's land and water surfaces, in the atmosphere, or in space, is important for both theory and applications, from an improved understanding of tectonic and magmatic processes to developing systems for mitigating the impact of natural hazards on society and the environment. Besides accurate positioning, all disturbances in the propagation of the transmitted GPS radio signals from satellite to receiver are mined for information, from troposphere and ionosphere delays for weather, climate, and natural hazard applications, to disturbances in the signals due to multipath reflections from the solid ground, water, and ice for environmental applications. We review the relevant concepts of geodetic theory, data analysis, and physical modeling for a myriad of processes at multiple spatial and temporal scales, and discuss the extensive global infrastructure that has been built to support GPS geodesy consisting of thousands of continuously operating stations. We also discuss the integration of heterogeneous and complementary data sets from geodesy, seismology, and geology, focusing on crustal deformation applications and early warning systems for natural hazards. PMID- 27552204 TI - Virulence profile: Rodney Donlan. PMID- 27552206 TI - AspireAssist--a new device for weight loss. PMID- 27552207 TI - Lifitegrast (Xiidra) for dry eye disease. PMID- 27552208 TI - Sugammadex (Bridion) for rapid reversal of neuromuscular blockade. PMID- 27552209 TI - An oral cholera vaccine for travelers (Vaxchora). PMID- 27552210 TI - Effect of Caffeine on Perceived Soreness and Functionality Following an Endurance Cycling Event. AB - Caldwell, AR, Tucker, MA, Butts, CL, McDermott, BP, Vingren, JL, Kunces, LJ, Lee, EC, Munoz, CX, Williamson, KH, Armstrong, LE, and Ganio, MS. Effect of caffeine on perceived soreness and functionality following an endurance cycling event. J Strength Cond Res 31(3): 638-643, 2017-Caffeine can reduce muscle pain during exercise; however, the efficacy of caffeine in improving muscle soreness and recovery from a demanding long-duration exercise bout has not been established. The purpose of this study was to investigate the effects of caffeine intake on ratings of perceived muscle soreness (RPMS) and perceived lower extremity functionality (LEF) following the completion of a 164-km endurance cycling event. Before and after cycling RPMS (1-to-6; 6 = severe soreness) and LEF (0-to-80; 80 = full functionality) were assessed by questionnaires. Subjects ingested 3 mg/kg body mass of caffeine or placebo pills in a randomized, double-blind fashion immediately after the ride and for the next 4 mornings (i.e., ~800 hours) and 3 afternoons (i.e., ~1200 hours). Before each ingestion, RPMS and LEF were assessed. Afternoon ratings of LEF were greater with caffeine ingestion the first day postride (65.0 +/- 6.1 vs. 72.3 +/- 6.7; for placebo and caffeine, respectively; p = 0.04), but at no other time points (p > 0.05). The caffeine group tended to have lower overall RPMS in the afternoon versus placebo (i.e., main effect of group; 1.1 +/- 0.2 vs. 0.5 +/- 0.2; p = 0.09). Afternoon RPMS for the legs was significantly lower in the caffeine group (main effect of caffeine; 1.3 +/- 0.2 vs. 0.5 +/- 0.3; p = 0.05). In conclusion, ingesting caffeine improved RPMS for the legs, but not LEF in the days following an endurance cycling event. Athletes may benefit from ingesting caffeine in the days following an arduous exercise bout to relieve feelings of soreness and reduced functionality. PMID- 27552212 TI - Effect of a Compressive Garment on Kinematics of Jump-Landing Tasks. AB - de Britto, MA, Lemos, AL, dos Santos, CS, Stefanyshyn, DJ, and Carpes, FP. Effect of a compressive garment on kinematics of jump-landing tasks. J Strength Cond Res 31(9): 2480-2488, 2017-During jump-landing tasks, knee kinematics such as excessive valgus have been linked to knee injury in females. We determine the influence of a compressive garment on knee valgus during landing. Physically active women (n = 27, mean age 23 years) performed 4 different jump-landing tasks with 2 apparel conditions (compressive garment and regular sports shorts). Kinematic data were collected to determine knee flexion and valgus angles and the maximum jump height. Results showed that the compressive garment decreased knee flexion and knee valgus range of motion, without significant changes in the maximum jump height. As a practical application, we suggest that compression could be a strategy to reduce dynamic valgus without influencing jump performance, which motivates further study of its potential for knee injury prevention. PMID- 27552214 TI - Hydrogen sulfide metabolism regulates endothelial solute barrier function. AB - Hydrogen sulfide (H2S) is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs) were isolated from wild type mice and mice lacking cystathionine gamma lyase (CSE), a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides. PMID- 27552215 TI - Concussions and Repercussions. AB - In their Perspective, Donald A. Redelmeier and Sheharyar Raza discuss the significance of Seena Fazel and colleagues' longitudinal study of traumatic brain injury (TBI)-associated outcomes. PMID- 27552216 TI - Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates. AB - Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis. PMID- 27552217 TI - Commercial Crop Yields Reveal Strengths and Weaknesses for Organic Agriculture in the United States. AB - Land area devoted to organic agriculture has increased steadily over the last 20 years in the United States, and elsewhere around the world. A primary criticism of organic agriculture is lower yield compared to non-organic systems. Previous analyses documenting the yield deficiency in organic production have relied mostly on data generated under experimental conditions, but these studies do not necessarily reflect the full range of innovation or practical limitations that are part of commercial agriculture. The analysis we present here offers a new perspective, based on organic yield data collected from over 10,000 organic farmers representing nearly 800,000 hectares of organic farmland. We used publicly available data from the United States Department of Agriculture to estimate yield differences between organic and conventional production methods for the 2014 production year. Similar to previous work, organic crop yields in our analysis were lower than conventional crop yields for most crops. Averaged across all crops, organic yield averaged 67% of conventional yield [corrected]. However, several crops had no significant difference in yields between organic and conventional production, and organic yields surpassed conventional yields for some hay crops. The organic to conventional yield ratio varied widely among crops, and in some cases, among locations within a crop. For soybean (Glycine max) and potato (Solanum tuberosum), organic yield was more similar to conventional yield in states where conventional yield was greatest. The opposite trend was observed for barley (Hordeum vulgare), wheat (Triticum aestevum), and hay crops, however, suggesting the geographical yield potential has an inconsistent effect on the organic yield gap. PMID- 27552218 TI - Analysis of Viral Diversity in Relation to the Recency of HIV-1C Infection in Botswana. AB - BACKGROUND: Cross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result. METHODS: The data comes from 854 time-points and 42 participants enrolled in a primary HIV 1C infection study in Botswana. Time points after treatment initiation or with evidence of multiplicity of infection were excluded from the final analysis. PwD was calculated from quasispecies generated using single genome amplification and sequencing. We evaluated the ability of PwD to correctly classify HIV infection recency within <130, <180 and <360 days post-seroconversion using Receiver Operator Characteristics (ROC) methods. Following a secondary PwD screening, we quantified the reduction in the relative false-recency rate (rFRR) of the BED and LAg assays while maintaining a sensitivity of either 75, 80, 85 or 90%. RESULTS: The final analytic sample consisted of 758 time-points from 40 participants. The PwD assay was more accurate in classifying infection recency for the 130 and 180 day cut-offs when compared with the recommended LAg and BED thresholds. A higher AUC statistic confirmed the superior predictive performance of the PwD assay for the three cut-offs. When used for combination screening, the PwD assay reduced the rFRR of the LAg assay by 52% and the BED assay by 57.8% while maintaining a 90% sensitivity for the 130 and 180-day cut-offs respectively. CONCLUSION: PwD can accurately determine HIV infection recency. A secondary PwD screening reduces misclassification and increases the accuracy of serologic-based assays. PMID- 27552219 TI - Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor alpha-Motoneurons. AB - The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to alpha-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically alpha-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of alpha-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor alpha-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of alpha-motoneurons of lateral gastrocnemius (LG). LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled alpha-motoneurons were detected by immunofluorescence (IF) using input-specific anti- VGLUT1 and anti VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG alpha-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG alpha motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG alpha-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models of injury is a prerequisite to propose it as a therapeutic method to improve inputs to selected group of alpha-motoneurons after damage. PMID- 27552220 TI - A Fast Alignment-Free Approach for De Novo Detection of Protein Conserved Regions. AB - BACKGROUND: Identifying conserved regions in protein sequences is a fundamental operation, occurring in numerous sequence-driven analysis pipelines. It is used as a way to decode domain-rich regions within proteins, to compute protein clusters, to annotate sequence function, and to compute evolutionary relationships among protein sequences. A number of approaches exist for identifying and characterizing protein families based on their domains, and because domains represent conserved portions of a protein sequence, the primary computation involved in protein family characterization is identification of such conserved regions. However, identifying conserved regions from large collections (millions) of protein sequences presents significant challenges. METHODS: In this paper we present a new, alignment-free method for detecting conserved regions in protein sequences called NADDA (No-Alignment Domain Detection Algorithm). Our method exploits the abundance of exact matching short subsequences (k-mers) to quickly detect conserved regions, and the power of machine learning is used to improve the prediction accuracy of detection. We present a parallel implementation of NADDA using the MapReduce framework and show that our method is highly scalable. RESULTS: We have compared NADDA with Pfam and InterPro databases. For known domains annotated by Pfam, accuracy is 83%, sensitivity 96%, and specificity 44%. For sequences with new domains not present in the training set an average accuracy of 63% is achieved when compared to Pfam. A boost in results in comparison with InterPro demonstrates the ability of NADDA to capture conserved regions beyond those present in Pfam. We have also compared NADDA with ADDA and MKDOM2, assuming Pfam as ground-truth. On average NADDA shows comparable accuracy, more balanced sensitivity and specificity, and being alignment-free, is significantly faster. Excluding the one-time cost of training, runtimes on a single processor were 49s, 10,566s, and 456s for NADDA, ADDA, and MKDOM2, respectively, for a data set comprised of approximately 2500 sequences. PMID- 27552221 TI - Ligand Binding at the 4-4 Agonist-Binding Site of the 42 nAChR Triggers Receptor Activation through a Pre-Activated Conformational State. AB - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is the most abundant subtype in the brain and exists in two functional stoichiometries: (alpha4)3(beta2)2 and (alpha4)2(beta2)3. A distinct feature of the (alpha4)3(beta2)2 receptor is the biphasic activation response to the endogenous agonist acetylcholine, where it is activated with high potency and low efficacy when two alpha4-beta2 binding sites are occupied and with low potency/high efficacy when a third alpha4-alpha4 binding site is occupied. Further, exogenous ligands can bind to the third alpha4-alpha4 binding site and potentiate the activation of the receptor by ACh that is bound at the two alpha4-beta2 sites. We propose that perturbations of the recently described pre-activation step when a third binding site is occupied are a key driver of these distinct activation properties. To investigate this, we used a combination of simple linear kinetic models and voltage clamp electrophysiology to determine whether transitions into the pre-activated state were increased when three binding sites were occupied. We separated the binding at the two different sites with ligands selective for the alpha4-beta2 site (Sazetidine-A and TC-2559) and the alpha4-alpha4 site (NS9283) and identified that when a third binding site was occupied, changes in the concentration-response curves were best explained by an increase in transitions into a pre-activated state. We propose that perturbations of transitions into a pre-activated state are essential to explain the activation properties of the (alpha4)3(beta2)2 receptor by acetylcholine and other ligands. Considering the widespread clinical use of benzodiazepines, this discovery of a conserved mechanism that benzodiazepines and ACh potentiate receptor activation via a third binding site can be exploited to develop therapeutics with similar properties at other cys-loop receptors. PMID- 27552223 TI - Sources of black carbon to the Himalayan-Tibetan Plateau glaciers. AB - Combustion-derived black carbon (BC) aerosols accelerate glacier melting in the Himalayas and in Tibet (the Third Pole (TP)), thereby limiting the sustainable freshwater supplies for billions of people. However, the sources of BC reaching the TP remain uncertain, hindering both process understanding and efficient mitigation. Here we present the source-diagnostic Delta(14)C/delta(13)C compositions of BC isolated from aerosol and snowpit samples in the TP. For the Himalayas, we found equal contributions from fossil fuel (46+/-11%) and biomass (54+/-11%) combustion, consistent with BC source fingerprints from the Indo Gangetic Plain, whereas BC in the remote northern TP predominantly derives from fossil fuel combustion (66+/-16%), consistent with Chinese sources. The fossil fuel contributions to BC in the snowpits of the inner TP are lower (30+/-10%), implying contributions from internal Tibetan sources (for example, yak dung combustion). Constraints on BC sources facilitate improved modelling of climatic patterns, hydrological effects and provide guidance for effective mitigation actions. PMID- 27552222 TI - A Diverse Family of Host-Defense Peptides (Piscidins) Exhibit Specialized Anti Bacterial and Anti-Protozoal Activities in Fishes. AB - Conventional antibiotics and other chemical-based drugs are currently one of the most common methods used to control disease-related mortality in animal agriculture. Use of the innate immune system to decrease disease related mortalities is a novel alternative to conventional drugs. One component of the innate immune system is the host-defense peptides, also known as antimicrobial peptides. Host-defense peptides are typically small, amphipathic, alpha-helical peptides with a broad-spectrum of action against viral, bacterial, fungal, and/or protozoal pathogens. Piscidins are host-defense peptides first discovered in the hybrid striped bass (white bass, Morone chrysops, x striped bass, M. saxatilis). In this paper we identify four new piscidin isoforms in the hybrid striped bass and describe their tissue distributions. We also determine the progenitor species of origin of each piscidin (orthology) and propose a revised nomenclature for this newly described piscidin family based on a three class system. The Class I piscidins (22 amino acids in length; striped bass and white bass piscidin 1 and piscidin 3) show broad-spectrum activity against bacteria and ciliated protozoans, while the Class III piscidins (55 amino acids in length; striped bass and white bass piscidin 6 and striped bass piscidin 7) primarily show anti protozoal activity. The Class II piscidins (44-46 amino acids in length; striped bass and white bass piscidin 4 and white bass piscidin 5) have a level of activity against bacteria and protozoans intermediate to Classes I and III. Knowledge of piscidin function and activity may help in the future development of disease-resistant lines of striped bass and white bass that could be used to produce superior hybrids for aquaculture. PMID- 27552224 TI - Recent Update on Radiation Dose Assessment for the State-of-the-Art Coronary Computed Tomography Angiography Protocols. AB - OBJECTIVES: This study aimed to measure the absorbed doses in selected organs for prospectively ECG-triggered coronary computed tomography angiography (CCTA) using five different generations CT scanners in a female adult anthropomorphic phantom and to estimate the effective dose (HE). MATERIALS AND METHODS: Prospectively ECG triggered CCTA was performed using five commercially available CT scanners: 64 detector-row single source CT (SSCT), 2 * 32-detector-row-dual source CT (DSCT), 2 * 64-detector-row DSCT and 320-detector-row SSCT scanners. Absorbed doses were measured in 34 organs using pre-calibrated optically stimulated luminescence dosimeters (OSLDs) placed inside a standard female adult anthropomorphic phantom. HE was calculated from the measured organ doses and compared to the HE derived from the air kerma-length product (PKL) using the conversion coefficient of 0.014 mSv?mGy-1?cm-1 for the chest region. RESULTS: Both breasts and lungs received the highest radiation dose during CCTA examination. The highest HE was received from 2 * 32-detector-row DSCT scanner (6.06 +/- 0.72 mSv), followed by 64-detector-row SSCT (5.60 +/- 0.68 and 5.02 +/- 0.73 mSv), 2 * 64-detector-row DSCT (1.88 +/- 0.25 mSv) and 320-detector-row SSCT (1.34 +/- 0.48 mSv) scanners. HE calculated from the measured organ doses were about 38 to 53% higher than the HE derived from the PKL-to-HE conversion factor. CONCLUSION: The radiation doses received from a prospectively ECG-triggered CCTA are relatively small and are depending on the scanner technology and imaging protocols. HE as low as 1.34 and 1.88 mSv can be achieved in prospectively ECG-triggered CCTA using 320-detector-row SSCT and 2 * 64-detector-row DSCT scanners. PMID- 27552225 TI - Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan. AB - Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDRBW and SDRGA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDRGA and SDRBW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine. PMID- 27552226 TI - The Immunologic Properties of Bone Morphogenic Protein Receptor IB Positive Subpopulation before and after Osteogenic Differentiation in Mouse Dermis. AB - We have previously reported that human dermal bone morphogenic protein receptor (BMPR) IB positive subpopulation had a high osteogenic differentiation potential and may be a promising cell source for allogeneic bone tissue engineering. In this study, the immunologic properties of dermal BMPR-IB+ subpopulation before and after osteogenic differentiation were reported. The results confirmed that dermal BMPR-IB+ cells possessed a similar osteogenic differentiation potential with bone marrow mesenchymal stromal cells in a mouse model. Furthermore, the expression of immune rejection-related surface antigens such as major histocompatibility class II and co-stimulatory proteins (CD40, CD80, and CD86) were absent on dermal BMPRIB+ cells. Dermal BMPRIB+ cells elicited no proliferation of allogeneic splenocytes and suppressed the proliferation of stimulated immune cells. Interestingly, osteogenic differentiation in vitro had no adverse effect on the immunological features of these cells. Most importantly, inducible NO synthase (iNOS) was involved in immunoregulatory effects by undifferentiated BMPRIB+ fibroblasts, whereas indoleamine 2,3-dioxygenase (IDO) activity was related to mediating immunomodulatory function by osteogenic differentiated BMPRIB+ fibroblasts. In conclusion, dermal BMPRIB+ cells have a low immunogenicity and possess immunosuppressive capacity before and after osteogenic differentiation in vitro, which would facilitate the allotransplantation in the future. However, mechanisms mediating immunoregulatory property between undifferentiated and osteogenic differentiated BMPRIB+ fibroblasts may be different and need further investigation. PMID- 27552227 TI - Significance of fully automated tests for the diagnosis of antiphospholipid syndrome. AB - Antiphospholipid antibodies (aPLs) can vary both immunologically and functionally, thus it is important to effectively and correctly identify their presence when diagnosing antiphospholipid syndrome. Furthermore, since many immunological/functional tests are necessary to measure aPLs, complete examinations are often not performed in many cases due to significant burden on the testing departments. To address this issue, we measured aPLs defined according to the classification criteria (anticardiolipin antibody: aCL) IgG/IgM and anti-beta2 glycoprotein I antibody (abeta2GPI) (IgG/IgM) as well as non criteria antibodies (aCL IgA, abeta2GPI IgA and abeta2GPI domain I), in a cohort of 211 patients (61 APS, 140 disease controls and 10 healthy individuals). APLs were measured using a fully automated chemiluminescent immunoassay instrument (BIO-FLASH(r)/ACL AcuStar(r)) and with conventional ELISA tests. We demonstrated that both sensitivity and accuracy of diagnosis of aCL IgG and abeta2GPI IgG were high, in agreement with the past reports. When multiple aPLs were examined, the accuracy of diagnosis increased. The proportion of APS patients that were positive for 2 or more types of aPLs (47/61, 77%) was higher than that of patients with systemic lupus erythematosus (SLE)(3/37, 9%), those with non-SLE connective tissues diseases (1/53,2%), those with other diseases or healthy volunteers. Based on these findings, it was concluded that the fully automated chemiluminescent immunoassay instrument, which allows the simultaneous evaluation of many types of aPLs, offers clear advantages for a more complete, more rapid and less labor-intensive alternative to running multiple ELISA and could help in better diagnosis for suspected APS patients. PMID- 27552228 TI - Patient Satisfaction with Community Health Service Centers as Gatekeepers and the Influencing Factors: A Cross-Sectional Study in Shenzhen, China. AB - PURPOSE: Shenzhen is the first pilot city in China implementing the gatekeeper policy, with community health service (CHS) centers as the gatekeepers. We aim to investigate patient satisfaction with this policy and its influencing factors in Shenzhen. METHODS: 3,848 patients visiting eight CHS centers in Shenzhen of China between May 1 and July 28, 2013 were recruited. We interviewed them using a structured questionnaire to investigate their satisfaction with the gatekeeper policy of CHS. Multivariable logistic regression models were used to identify influencing factors. RESULTS: Of the respondents, 28.17%, 47.27% and 24.56% were satisfied with, neutral to, and not satisfied with the gatekeeper policy respectively. Patient satisfaction with this policy was found to be associated with education level, familiarity with the policy, referral experience, satisfaction with convenience of seeing a doctor, satisfaction with waiting time, satisfaction with medical facility, satisfaction with general medical practitioners' professional skill, and proportion of expense reimbursed. CONCLUSIONS: Our investigation shows that patient satisfaction with the gatekeeper policy was low. To improve patient satisfaction, efforts should be made to increase the convenience of seeing a doctor in community, shorten waiting time, improve general medical practitioners' professional skill, and increase proportion of expense reimbursement. PMID- 27552229 TI - The Arachidonate 15-Lipoxygenase Enzyme Product 15-HETE Is Present in Heart Tissue from Patients with Ischemic Heart Disease and Enhances Clot Formation. AB - Ischemic heart disease is a major cause of death and morbidity and the search for novel therapeutic targets is still required. We have previously shown that the enzyme arachidonate 15 lipoxygenase (ALOX15), which catalyzes the conversion of arachidonic acid to 15-hydroxy eicosatetraenoic acid (15-HETE), is highly expressed in ischemic heart tissue, but its role in the pathogenesis of ischemic heart disease is unclear. Here we showed that expression of ALOX15, but not ALOX12 or ALOX15B, was increased in ischemic versus non-ischemic human heart biopsy samples. A similar ALOX expression pattern was found in hypoxic human cardiomyocytes and cardiac endothelial cells. We also showed that levels of 15 HETE were significantly higher in ischemic versus non-ischemic human heart biopsy samples and showed a tendency to increase in serum from the patients with ischemic heart disease. Moreover, hypoxia increased the production of 15-HETE levels from human cardiomyocytes and cardiac endothelial cells. The hypoxia induced increase in 15-HETE levels from human cardiomyocytes was inhibited by the ALOX15 inhibitor baicalein. Finally, by using intrinsic rotational thromboelastometry, we showed that human whole blood clotted faster in the presence of 15-HETE. In summary, we propose that increased ALOX15 expression in heart tissue under ischemic conditions may lead to increased production of 15 HETE, potentially contributing to thrombosis. PMID- 27552230 TI - Molecular Characterization of Salmonella enterica Serovar Aberdeen Negative for H2S Production in China. AB - Salmonella enterica infections continue to be a significant burden on public health worldwide. The ability of S. enterica to produce hydrogen sulfide (H2S) is an important phenotypic characteristic used to screen and identify Salmonella with selective medium; however, H2S-negative Salmonella have recently emerged. In this study, the H2S phenotype of Salmonella isolates was confirmed, and the selected isolates were subjected to antimicrobial susceptibility testing and molecular identification by multilocus sequence typing, pulsed-field gel electrophoresis, and clustered regularly interspaced short palindromic repeat (CRISPR) analysis. The phs genetic operon was also analyzed. A total of 160 S. enterica serovar Aberdeen isolates were detected between 2005 and 2013 in China. Of them, seven non-H2S-producing isolates were detected. Notably, four samples yielded four pairs of isolates with different H2S phenotypes, simultaneously. The data demonstrated that H2S-negative isolates were genetically closely related to H2S-positive isolates. Three new spacers (Abe1, Abe2, and Abe3) were identified in CRISPR locus 1 in four pairs of isolates with different H2S phenotypes from the same samples. Sequence analysis revealed a new nonsense mutation at position 208 in the phsA gene of all non-H2S-producing isolates. Additionally, we describe a new screening procedure to avoid H2S-negative Salmonella, which would normally be overlooked during laboratory and hospital screening. The prevalence of this pathogen may be underestimated; therefore, it is important to focus on improving surveillance of this organism to control its spread. PMID- 27552231 TI - Reflection and Phase Matching in Plasmonic Gold Tapers. AB - We investigate different dynamic mechanisms, reflection and phase matching, of surface plasmons in a three-dimensional single-crystalline gold taper excited by relativistic electrons. Plasmonic modes of gold tapers with various opening angles from 5 degrees to 47 degrees are studied both experimentally and theoretically, by means of electron energy-loss spectroscopy and finite difference time-domain numerical calculations, respectively. Distinct resonances along the taper shaft are observed in tapers independent of opening angles. We show that, despite their similarity, the origin of these resonances is different at different opening angles and results from a competition between two coexisting mechanisms. For gold tapers with large opening angles (above ~20 degrees ), phase matching between the electron field and that of higher-order angular momentum modes of the taper is the dominant contribution to the electron energy-loss because of the increasing interaction length between electron and the taper near field. In contrast, reflection from the taper apex dominates the EELS contrast in gold tapers with small opening angles (below ~10 degrees ). For intermediate opening angles, a gradual transition of these two mechanisms was observed. PMID- 27552233 TI - The validity and reliability of a sample of 10 Wattbike cycle ergometers. AB - The purpose of the study was to assess the validity and inter-bike reliability of 10 Wattbike cycle ergometers, and to assess the test-retest reliability of one Wattbike. Power outputs from 100 to 1000 W were applied using a motorised calibration rig (LODE) at cadences of 70, 90, 110 and 130 rev . min-1, which created nineteen different intensities for comparison. Significant relationships (P < 0.01, r2 = 0.99) were found between each of the Wattbikes and the LODE. Each Wattbike was found to be valid and reliable and had good inter-bike agreement. Within-bike mean differences ranged from 0.0 W to 8.1 W at 300 W and 3.3 W to 19.3 W at 600 W. When taking into account the manufacturers stated measurement error for the LODE (2%), the mean differences were less than 2%. Comparisons between Wattbikes at each of the nineteen intensities gave differences from 0.6 to 25.5 W at intensities of 152 W and 983 W, respectively. There was no significant difference (P > 0.05) between the measures of power recorded in the test-retest condition. The data suggest that the Wattbike is an accurate and reliable tool for training and performance assessments, with data between Wattbikes being able to be used interchangeably. PMID- 27552232 TI - Tuning the Structure and Photophysics of a Fluorous Phthalocyanine Platform. AB - Phthalocyanines are an important class of industrial dyes with potential commercial applications ranging from photovoltaics to biomedical imaging and therapeutics. We previously demonstrated the versatility of the commercially available zinc(II) hexadecafluorophthalocyanine (ZnF16Pc) as a platform for rapidly developing functional materials for these applications and more. Because this core-platform approach to dye development is increasingly common, it is important to understand the photophysical and structural consequences of the substitution chemistry involved. We present a fundamental study of a series of ZnF16Pc derivatives in which the aromatic fluorine atoms are progressively substituted with thioalkanes. Clear spectroscopic trends are observed as the substituents change from electron-withdrawing to electron-releasing groups. Additionally, there is evidence for significant structural distortion of the normally planar heterocycle, with important ramifications for the photophysics. These results are also correlated to DFT calculations, which show that the orbital energies and symmetries are both important factors for explaining the excited-state dynamics. PMID- 27552234 TI - Highly Cross-Linked Epoxy Nanofiltration Membranes for the Separation of Organic Chemicals and Fish Oil Ethyl Esters. AB - Membrane separations are highly desired for the chemical industry because they are inexpensive, avoid the use of heat, can be applied to the purification of a wide range of chemicals, and can be scaled to industrial levels. Separating chemicals with molecular weights between 100 and 300 g mol(-1) remains a significant challenge in the field of organic solvent nanofiltration (OSN) due to their similar sizes and rotational flexibility. In this work, we report the fabrication of poly(epoxy) membranes that show excellent selectivity of over 100:1 for chemicals in this range. The membranes are easily tuned to obtain different flux and selectivity by using interchangeable amine and epoxide monomers. These membranes were used to separate the important nutritional omega-3 fatty acid ethyl esters eicosapentaenoic ethyl ester (EPA-EE) and docosahexaenoic acid ethyl ester (DHA-EE) from each other, despite a small difference in molecular weight (26 g mol(-1)). This is the first example of a separation of EPA EE and DHA-EE using a membrane process. PMID- 27552236 TI - Spontaneous Intracranial Hypotension: An Etiology for Consciousness Disorder and Coma. AB - We report 3 cases of spontaneous intracranial hypotension (SIH) associated with consciousness disorder and coma. In patients, SIH was suspected on a computed tomography scan and diagnosed by cerebral magnetic resonance imaging (MRI). Spinal MRI confirmed cerebrospinal fluid leakage. SIH should be seen as an underestimated cause of consciousness disorder and coma, especially in patients with a history of orthostatic headache, spinal injury, or oculomotor signs. Computed tomography scans should be examined for signs of SIH before operating on patients with a spontaneous subdural hematoma. Brain and spine MRI should be performed when SIH is suspected. Our 3 patients have shown good recovery without any neurological sequelae. PMID- 27552235 TI - Multiscale Quantum Mechanics/Molecular Mechanics Simulations with Neural Networks. AB - Molecular dynamics simulation with multiscale quantum mechanics/molecular mechanics (QM/MM) methods is a very powerful tool for understanding the mechanism of chemical and biological processes in solution or enzymes. However, its computational cost can be too high for many biochemical systems because of the large number of ab initio QM calculations. Semiempirical QM/MM simulations have much higher efficiency. Its accuracy can be improved with a correction to reach the ab initio QM/MM level. The computational cost on the ab initio calculation for the correction determines the efficiency. In this paper we developed a neural network method for QM/MM calculation as an extension of the neural-network representation reported by Behler and Parrinello. With this approach, the potential energy of any configuration along the reaction path for a given QM/MM system can be predicted at the ab initio QM/MM level based on the semiempirical QM/MM simulations. We further applied this method to three reactions in water to calculate the free energy changes. The free-energy profile obtained from the semiempirical QM/MM simulation is corrected to the ab initio QM/MM level with the potential energies predicted with the constructed neural network. The results are in excellent accordance with the reference data that are obtained from the ab initio QM/MM molecular dynamics simulation or corrected with direct ab initio QM/MM potential energies. Compared with the correction using direct ab initio QM/MM potential energies, our method shows a speed-up of 1 or 2 orders of magnitude. It demonstrates that the neural network method combined with the semiempirical QM/MM calculation can be an efficient and reliable strategy for chemical reaction simulations. PMID- 27552237 TI - Management of 1-Lung Ventilation in a Patient With Failing Fontan Circulation. AB - The number of patients reaching adulthood after undergoing Fontan palliation for the repair of a congenital heart defect continues to increase. In this case report, we present the anesthetic management of a patient with a history of tricuspid atresia treated with palliative Fontan repair who had developed clinical evidence of Fontan failure. He presented with septic shock secondary to streptococcal toxic shock syndrome complicated by a loculated pleural effusion. He underwent open thoracic decortication under 1-lung ventilation. Discussion focuses on the management of volume status and pulmonary vascular resistance as well as surgical implications of Fontan physiology in thoracic surgery. PMID- 27552238 TI - Upper Extremity Peripheral Intravenous Line Infiltration With Concomitant Loss of Pulses Treated With Lipoaspiration: A Case Report. AB - Peripheral intravenous cannulation in children is associated with occasional morbidity. We present a case where a large volume of blood, administered through a small peripheral cannula in the antecubital fossa, was found to have extravasated into the soft tissues, causing catastrophic vascular compromise. The expedient removal of the extravasate using a lipoaspiration cannula restored perfusion immediately to the affected limb and negated the need for surgical fasciotomies. PMID- 27552239 TI - A Rare Case of Hydromorphone-Induced Angioedema Effectively Managed by a Difficult Airway Response Team. AB - Hydromorphone, unlike other opioids associated with histamine release, has never been reported to cause angioedema. We report a rare case of hydromorphone-induced angioedema in a 34-year-old woman with history of deep venous thrombosis and pulmonary embolism who presented with leg swelling and pain after trauma. Hydromorphone was administered with subsequent rapid development of stridor and edematous changes of the tongue, uvula, and surrounding mucosa. The difficult airway response team was activated, and the airway was secured by emergent awake fiberoptic intubation in the operating room. After being treated with antihistamines and steroids for 24 hours, the airway edema had resolved, leading to a successful extubation. PMID- 27552240 TI - Preoperative Assessment of the Impact of Positive Pressure Ventilation With Noninvasive Positive Pressure Ventilation in a Patient With Eisenmenger Syndrome: A Case Study. AB - In Eisenmenger syndrome (ES), positive pressure ventilation (PPV) during general anesthesia may lead to an increase in pulmonary vascular resistance and potentially to hypoxemia. In an attempt to predict the patient's hemodynamic response to intraoperative ventilation, we tested preoperatively the hemodynamic effects of noninvasive PPV with continuous positive pressure in a woman with ES scheduled for oophorectomy. The surgery was performed without complications, and the patient was discharged on postoperative day 8. PMID- 27552241 TI - Lessons Still Being Learned: Acute Pulmonary Tumor Embolus During Renal Cell Carcinoma Resection. AB - Renal cell carcinoma (RCC) is the most common primary renal neoplasm and is associated with the intraluminal growth into the venous system with possible extension into the inferior vena cava or even right heart. Intraoperative pulmonary embolism is a complication of resection of RCC, which may be mitigated by the use of the cardiopulmonary bypass with or without deep hypothermic circulatory arrest. We present a case of unexpected pulmonary embolism diagnosed during RCC surgery. The case highlights the central importance of intraoperative transesophageal echocardiography use and the need for proper preoperative planning for the use of cardiopulmonary bypass. PMID- 27552242 TI - The First Case Report of Anaphylaxis Caused by the Inclusion Complex of Rocuronium and Sugammadex. AB - A 50-year-old man developed a severe anaphylactic reaction shortly after the administration of sugammadex at the end of an uneventful laparoscopic appendectomy. Subsequent skin testing was negative to all agents to which the patient was exposed including sugammadex. Because of the temporal relationship to the administration of sugammadex, further skin testing was performed with premixed sugammadex and rocuronium that produced a markedly positive response. This is the first case report of anergy to the individual components but sensitivity to the inclusion complex of rocuronium and sugammadex. Written informed consent was obtained from the patient for skin testing, photography, laser perfusion imaging, and publication of this case report. PMID- 27552243 TI - Iatrogenic Pseudoaneurysm After Continuous Adductor Canal Block. AB - No major complications have been associated with the ultrasound-guided continuous adductor canal block (cACB). We present a case of iatrogenic pseudoaneurysm in a branch of the superficial femoral artery in a 44-year-old patient after a cACB for knee surgery. Both anesthesia and surgery were completed uneventfully. The postoperative day 3 examination showed a complete quadricep impairment and a large hematoma in a medial-anterior part of the thigh, and laboratory tests reported hemoglobin = 7.2 g dL. The computed tomography scan revealed the pseudoaneurysm (16 * 16 * 18 mm) that was successfully embolized after selective catheterization. The patient was discharged regularly on postoperative day 12. PMID- 27552244 TI - Domestic helpers as frontline workers in China's home-based elder care: A systematic review. AB - We conducted a systematic review of the existing empirical studies focusing on Chinese domestic helpers in mainland China and foreign domestic helpers in Hong Kong who provide care for community-dwelling older adults. There are very limited studies specifically focusing on this population. The findings synthesized domestic helpers' characteristics, acknowledged their contributions to elder care in China, and showed multiple challenges facing them, such as issues related to their physical health and emotional well-being, lack of legal rights protection, difficulties of adapting life in the host city, lack of training, and risk of abuse and sexual harassment. Our findings support the need for developing training and educational programs about legal rights protection and cultural competency for domestic helpers and the need to promote domestic helpers' access to health care and social welfare and opportunities for career advancement, and provide respectful working conditions. PMID- 27552246 TI - On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen. AB - The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed. PMID- 27552245 TI - A Metal-Amino Acid Complex-Derived Bifunctional Oxygen Electrocatalyst for Rechargeable Zinc-Air Batteries. AB - Bifunctional oxygen electrocatalyst: A metal-amino acid complex is developed to prepare high-performance mesoporous carbon electrocatalyst for both oxygen reduction and oxygen evolution reactions. Such prepared catalyst can be used to assemble rechargeable zinc-air batteries with excellent durability. This work represents a new route toward low-cost, highly active, and durable bifunctional electrocatalysts for cutting-edge energy conversion devices. PMID- 27552248 TI - Pathogenic Phenotype of Adipogenesis and Hyaluronan in Orbital Fibroblasts From Female Graves' Orbitopathy Mouse Model. AB - A mouse model of Graves' orbitopathy (GO) induced by genetic immunization of human TSH receptor (TSHR) A-subunit encoding plasmid has recently been established. The orbital pathology was characterized by adipogenesis, myopathy and fibrosis. Human orbital fibroblasts (OFs) express TSHR and IGF-1 receptor (IGF-1R) and are considered to be pathogenic in GO. We established conditions for growing ex vivo cultures of mouse OFs (mOFs) from orbital tissue of animals undergoing GO and controls. Early passage mOFs showed characteristic fibroblast morphology and expressed mesenchymal stem cell markers including a strong expression of CD90.2 and CD40, whereas display of CD73 and all other leucocyte markers was uniformly absent. Importantly, OFs derived from GO mice expressed elevated levels of TSHR and IGF-1R and showed enhanced adipogensis compared with controls. Activation of TSHR in mOFs from GO animals with TSH, monoclonal thyroid stimulating antibody M22, or stimulation of IGF-1R with IGF-1-induced hyaluronan secretion to significantly elevated levels compared with control animals. Hyaluronan synthase 2 was more abundant in OFs derived from GO mice. In conclusion, mOFs established from GO model recapitulate the pathogenicity of human OFs from GO patients by their increased propensity for adipogenesis and hyaluronan production leading to disease activity. To our knowledge, this is the first report to show mOFs from the preclinical GO model have pathogenic properties that will aid in understanding the molecular and genetic changes during progression to adipogenesis and hyaluronan deposition to provide new insights into GO pathogenesis. PMID- 27552247 TI - Nonnuclear Estrogen Receptor Activation Improves Hepatic Steatosis in Female Mice. AB - Estrogens have the potential to afford atheroprotection, to prevent excess adiposity and its metabolic complications including insulin resistance, and to lessen hepatic steatosis. Cellular responses to estrogens occur through gene regulation by nuclear estrogen receptors (ERs), and through signal initiation by plasma membrane-associated ER. Leveraging the potentially favorable cardiometabolic actions of estrogens has been challenging, because their reproductive tract and cancer-promoting effects adversely impact the risk to benefit ratio of the therapy. In previous works, we discovered that an estrogen dendrimer conjugate (EDC) comprised of ethinyl-estradiol (E2) molecules linked to a poly(amido)amine dendrimer selectively activates nonnuclear ER, and in mice, EDC does not invoke a uterotrophic response or support ER-positive breast cancer growth. In the present investigation, we employed EDC to determine how selective nonnuclear ER activation impacts atherosclerosis, adiposity, glucose homeostasis, and hepatic steatosis in female mice. In contrast to E2, EDC did not blunt atherosclerosis in hypercholesterolemic apoE-/- mice. Also in contrast to E2, EDC did not prevent the increase in adiposity caused by Western diet feeding in wild type mice, and it did not affect Western diet-induced glucose intolerance. However, E2 and EDC had comparable favorable effect on diet-induced hepatic steatosis, and this was related to down-regulation of fatty acid and triglyceride synthesis genes in the liver. Predictably, only E2 caused a uterotrophic response. Thus, although nonnuclear ER activation does not prevent atherosclerosis or diet-induced obesity or glucose intolerance, it may provide a potential new strategy to combat hepatic steatosis without impacting the female reproductive tract or increasing cancer risk. PMID- 27552249 TI - Arterial stiffness in children with and without probable developmental coordination disorder. AB - BACKGROUND: Children with cardiovascular disease risk factors demonstrate adverse arterial alterations that are predictive of cardiovascular morbidity and mortality in adults. Children with developmental coordination disorder (DCD) are at cardiovascular risk as they are more likely to be obese and inactive. AIM: The purpose of this study was to assess arterial structure and function in children with and without probable DCD (p-DCD). METHODS: A cross-sectional study of 33 children with p-DCD (22 male) and 53 without (30 male). The Movement Assessment Battery for Children was used to classify those with p-DCD. Adiposity was assessed using the BOD POD. Compliance, distensibility, and intima-media thickness were measured at the common carotid artery (CCA). ECG R-wave-to-toe pulse wave velocity (PWV) was also measured. RESULTS: Compared to controls, males with p-DCD had lower CCA distensibility (p=0.034) and higher PWV (p=0.001). No differences were evident in females. Body fat percent was a significant predictor of CCA distensibility and removed the effect of p-DCD on PWV in males. CONCLUSIONS: The present study demonstrates augmented arterial stiffness in males with p-DCD, likely attributed to body fat. These findings underscore the importance of targeted interventions in children with p-DCD, specifically males, in order to prevent future cardiovascular risk. PMID- 27552250 TI - Bridging the gap. AB - A new study reveals that a protein called talin forms a vital link between microtubules and focal adhesions at the surface of cells. PMID- 27552252 TI - Glycyrrhizic Acid Decreases Gentamicin-Resistance in Vancomycin-Resistant Enterococci. AB - The resistance of commensal bacteria against first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. Particularly vancomycin-resistant Enterococcus faecium represents an increasing clinical problem in the treatment of infectious diseases and hinders adequate antibiotic stewardship. In consideration of the lack of novel antibiotic compounds, the development of resistance-modifying agents, however, can mitigate the spread of bacterial drug resistance and might possibly extend the useful application indices of an existing licensed antibiotic. Given that saponins modify the local chemical environment at cell membranes and might modify the uptake or mode of action of antibiotics in bacteria, we investigated the influence of the triterpenoid saponin glycyrrhizic acid of Glycyrrhiza glabra on the susceptibility of vancomycin-resistant enterococci against the aminoglycoside antibiotic gentamicin in 47 clinical isolates by applying the checkerboard method. The fractional inhibitory concentration indices values were determined between 0.016 and <= 0.5 (synergy is accepted with values <= 0.5). Glycyrrhizic acid at the subinhibitory concentration of 2.4 mM was found to reduce the minimal inhibitory concentration of gentamicin in intrinsically resistant E. faecium strains down to 6.25 % of the minimal inhibitory concentration of gentamicin alone, whereas relatively low concentrations of glycyrrhizic acid (18 uM) resulted in increased susceptibilities for some E. faecium isolates to gentamicin. In conclusion, our study points towards a therapeutic potential of glycyrrhizic acid in co application with gentamicin for defined local bacterial infections caused by vancomycin resistant Enterococcus strains. PMID- 27552251 TI - Use of a cocktail probe to assess potential drug interactions with cytochrome P450 after administration of belatacept, a costimulatory immunomodulator. AB - AIM: This open-label study investigated the effect of belatacept on cytokine levels and on the pharmacokinetics of caffeine, losartan, omeprazole, dextromethorphan and midazolam, as CYP probe substrates after oral administration of the Inje cocktail in healthy volunteers. METHODS: Twenty-two evaluable subjects received the Inje cocktail on Days 1, 4, 7 and 11 and belatacept infusion on Day 4. RESULTS: Since belatacept caused no major alterations to cytokine levels, there were no major effects on CYP-substrate pharmacokinetics, except for a slight (16-30%) increase in omeprazole exposure, which was probably due to omeprazole-mediated, time-dependent CYP inhibition. Belatacept did not cause major alterations in the pharmacokinetics, as measured by the geometric mean ratios and associated 90% confidence interval for area under the plasma concentration -time curve from time zero to infinity on Day 7 comparing administration with and without belatacept for caffeine (1.002 [0.914, 1.098]), dextromethorphan (1.031 [0.885, 1.200]), losartan (1.016 [0.938, 1.101)], midazolam (0.968 [0.892, 1.049]) or their respective metabolites. CONCLUSIONS: Therefore, no dose adjustments of CYP substrates are indicated with belatacept coadministration. PMID- 27552253 TI - Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway. AB - Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the glomeruli. Endothelial dysfunction is an early sign of diabetic cardiovascular disease and may contribute to progressive diabetic nephropathy. Hyperglycemia-induced endothelial hyperpermeability is crucial to diabetic nephropathy. Rutin has beneficial effects on diabetic nephropathy, but the exact mechanisms of its protective effect remain elusive. The aim of this study was to assess the role of pretreatment with rutin in an in vitro model of hyperglycemia-induced barrier dysfunction in human renal glomerular endothelial cells. Human renal glomerular endothelial cells were exposed to rutin and/or hyperglycemia for 24 h. Hyperglycemia increased permeability and decreased the junction protein occludin in the cell-cell junction area and the total expression in human renal glomerular endothelial cells, whereas rutin treatment significantly corrected these abnormalities. Furthermore, hyperglycemia-induced activation of RhoA/ROCK was reversed by treatment with rutin or the knockdown of ROCK2. Interestingly, rutin prevented hyperglycemia-induced hyperpermeability, and dysfunction of the tight junction, a high level of reactive oxygen species, and activation of RhoA/ROCK were significantly abolished with the knockdown of Nrf2. In conclusion, rutin significantly prevented hyperglycemia-disrupted renal endothelial barrier function by inhibiting the RhoA/ROCK signaling pathway through decreasing reactive oxygen species, which was mediated by the activation of Nrf2. Our results may explain, at least in part, some beneficial effects of rutin that may be applicable to the treatment of vascular disorders in diabetic nephropathy. PMID- 27552254 TI - Perceptual learning effect on decision and confidence thresholds. AB - Practice can enhance of perceptual sensitivity, a well-known phenomenon called perceptual learning. However, the effect of practice on subjective perception has received little attention. We approach this problem from a visual psychophysics and computational modeling perspective. In a sequence of visual search experiments, subjects significantly increased the ability to detect a "trained target". Before and after training, subjects performed two psychophysical protocols that parametrically vary the visibility of the "trained target": an attentional blink and a visual masking task. We found that confidence increased after learning only in the attentional blink task. Despite large differences in some observables and task settings, we identify common mechanisms for decision making and confidence. Specifically, our behavioral results and computational model suggest that perceptual ability is independent of processing time, indicating that changes in early cortical representations are effective, and learning changes decision criteria to convey choice and confidence. PMID- 27552255 TI - 27-GAUGE NEEDLE-ASSISTED TECHNIQUE FOR REPOSITIONING A DISLOCATED INTRAOCULAR LENS. AB - BACKGROUND: Several techniques for the reposition of a posterior chamber intraocular lens (IOL) posterior dislocating into the vitreous cavity have been developed. However, most of these methods are complicated or include externalizing part of the IOL from a corneal or scleral wound. We here describe a 27-gauge needle-assisted technique for management of a dislocated posterior chamber IOL. METHODS: This is a retrospective, noncomparative, interventional case series that discusses the results of 27-gauge needle-assisted reposition of the posterior chamber IOL with transscleral sulcus fixation in 5 consecutive cases with an IOL dislocated into vitreous cavity. These patients underwent IOL reposition with the above-mentioned technique between April 2013 and October 2014 and were followed up for at least two months thereafter. RESULTS: The IOLs of the five cases were stable with proper centrations. The postoperative best-corrected visual acuity ranged from 20/30 to 20/20. CONCLUSION: The technique of 27-gauge needle-assisted reposition of the posterior chamber IOL with transscleral fixation is effective for reposition of a dislocated IOL. This technique provides good IOL fixation without creating a large corneal wound or scleral flap. PMID- 27552256 TI - Rapid Development of Wet Adhesion between Carboxymethylcellulose Modified Cellulose Surfaces Laminated with Polyvinylamine Adhesive. AB - The surface of regenerated cellulose membranes was modified by irreversible adsorption of carboxymethylcellulose (CMC). Pairs of wet CMC-modified membranes were laminated with polyvinylamine (PVAm) at room temperature, and the delamination force for wet membranes was measured for both dried and never-dried laminates. The wet adhesion was studied as a function of PVAm molecular weight, amine content, and deposition pH of the polyelectrolyte. Surprisingly the PVAm CMC system gave substantial wet adhesion that exceeded that of TEMPO-oxidized membranes with PVAm for both dried and never-dried laminates. The greatest wet adhesion was achieved for fully hydrolyzed high molecular weight PVAm. Bulk carboxymethylation of cellulose membranes gave inferior wet adhesion combined with PVAm as compared to CMC adsorption which indicates that a CMC layer of the order of 10 nm was necessary. There are no obvious covalent cross-linking reactions between CMC and PVAm at room temperature, and on the basis of our results, we are instead attributing the wet adhesion to complex formation between the PVAm and the irreversibly adsorbed CMC at the cellulose surface. We propose that interdigitation of PVAm chains into the CMC layer is responsible for the high wet adhesion values. PMID- 27552257 TI - Exploring the Dependence of QM/MM Calculations of Enzyme Catalysis on the Size of the QM Region. AB - Although QM/MM calculations are the primary current tool for modeling enzymatic reactions, the reliability of such calculations can be limited by the size of the QM region. Thus, we examine in this work the dependence of QM/MM calculations on the size of the QM region, using the reaction of catechol-O-methyl transferase (COMT) as a test case. Our study focuses on the effect of adding residues to the QM region on the activation free energy, obtained with extensive QM/MM sampling. It is found that the sensitivity of the activation barrier to the size of the QM is rather limited, while the dependence of the reaction free energy is somewhat larger. Of course, the results depend on the inclusion of the first solvation shell in the QM regions. For example, the inclusion of the Mg(2+) ion can change the activation barrier due to charge transfer effects. However, such effects can easily be included in semiempirical approaches by proper parametrization. Overall, we establish that QM/MM calculations of activation barriers of enzymatic reactions are not highly sensitive to the size of the QM region, beyond the immediate region that describes the reacting atoms. PMID- 27552259 TI - Palbociclib and tumor suppressor gene activation. PMID- 27552258 TI - Electrocardiographic Time to Intrinsicoid Deflection and Heart Failure: The Multi Ethnic Study of Atherosclerosis. AB - BACKGROUND: Time to intrinsicoid deflection (ID), the time from onset of the QRS complex to the peak of the R wave on the electrocardiogram, represents delayed ventricular activation and suggests that impaired myocardial function is present. It is unknown whether delayed time to ID is predictive of future heart failure (HF) events. HYPOTHESIS: Delayed time to ID is predictive of future HF events. METHODS: A total of 6394 participants (mean age, 62 +/- 10 years; 54% women; 38% whites, 28% blacks, 22% Hispanics, 12% Chinese Americans) without clinically apparent cardiovascular disease or major ventricular conduction delay (QRS >=120 ms) from the Multi-Ethnic Study of Atherosclerosis were included. Time to ID was automatically measured from baseline electrocardiograms (2000-2002) as the maximum value in leads V5 and V6 . Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time to ID and HF. RESULTS: Over a median follow-up of 11.2 years, a total of 217 (3.4%) participants developed HF (incidence rate per 1000 person-years: 3.33, 95% CI: 2.91-3.80). In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, each 10-ms increase in maximum time to ID was associated with an increased risk for HF (HR: 1.42, 95% CI: 1.15-1.74). The results remained similar when stratified by age, sex, and race/ethnicity. CONCLUSIONS: Delayed time to ID is able to identify individuals at risk for developing HF before major ventricular conduction delays (eg, bundle branch block) are evident. PMID- 27552260 TI - Prevalence and Causes of Paralysis-United States, 2013. AB - OBJECTIVES: To estimate the prevalence and causes of functional paralysis in the United States. METHODS: We used the 2013 US Paralysis Prevalence & Health Disparities Survey to estimate the prevalence of paralysis, its causes, associated sociodemographic characteristics, and health effects among this population. RESULTS: Nearly 5.4 million persons live with paralysis. Most persons with paralysis were younger than 65 years (72.1%), female (51.7%), White (71.4%), high school graduates (64.8%), married or living with a partner (47.4%), and unable to work (41.8%). Stroke is the leading cause of paralysis, affecting 33.7% of the population with paralysis, followed by spinal cord injury (27.3%), multiple sclerosis (18.6%), and cerebral palsy (8.3%). CONCLUSIONS: According to the functional definition, persons living with paralysis represent a large segment of the US population, and two thirds of them are between ages 18 and 64 years. Targeted health promotion that uses inclusion strategies to account for functional limitations related to paralysis can be undertaken in partnership with state and local health departments. PMID- 27552261 TI - Prevalence of Hearing Loss by Severity in the United States. AB - OBJECTIVES: To estimate the age- and severity-specific prevalence of hearing impairment in the United States. METHODS: We conducted cross-sectional analyses of 2001 through 2010 data from the National Health and Nutrition Examination Survey on 9648 individuals aged 12 years or older. Hearing loss was defined as mild (> 25 dB through 40 dB), moderate (> 40 dB through 60 dB), severe (> 60 dB through 80 dB), or profound (> 80 dB). RESULTS: An estimated 25.4 million, 10.7 million, 1.8 million, and 0.4 million US residents aged 12 years or older, respectively, have mild, moderate, severe, and profound better-ear hearing loss. Older individuals displayed a higher prevalence of hearing loss and more severe levels of loss. Across most ages, the prevalence was higher among Hispanic and non-Hispanic Whites than among non-Hispanic Blacks and was higher among men than women. CONCLUSIONS: Hearing loss directly affects 23% of Americans aged 12 years or older. The majority of these individuals have mild hearing loss; however, moderate loss is more prevalent than mild loss among individuals aged 80 years or older. PUBLIC HEALTH IMPLICATIONS: Our estimates can inform national public health initiatives on hearing loss and help guide policy recommendations currently being discussed at the Institute of Medicine and the White House. PMID- 27552262 TI - Toward a Regulatory Framework for the Waterpipe. AB - Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe cafe setting, and its marketing environment dominated by Internet promotion. PMID- 27552263 TI - Population-Attributable Risk Percentages for Racialized Risk Environments. AB - Research about relationships between place characteristics and racial/ethnic inequities in health has largely ignored conceptual advances about race and place within the discipline of geography. Research has also almost exclusively quantified these relationships using effect estimates (e.g., odds ratios), statistics that fail to adequately capture the full impact of place characteristics on inequities and thus undermine our ability to translate research into action. We draw on geography to further develop the concept of "racialized risk environments," and we argue for the routine calculation of race/ethnicity-specific population-attributable risk percentages. PMID- 27552264 TI - Human Papillomavirus Vaccination Requirements in US Schools: Recommendations for Moving Forward. AB - Safe and effective human papillomavirus (HPV) vaccines have been available and recommended for adolescents for a decade in the United States, yet vaccination rates remain suboptimal. School entry requirements have increased uptake of other vaccines for adolescents and made coverage more equitable. However, only 3 jurisdictions require HPV vaccine for school. We summarize the current status of HPV vaccine requirements and discuss the rationales for and against these policies. The rationales for requirements include HPV vaccine efficacy and safety, effectiveness of requirements for increasing vaccine uptake and making it more equitable, and use of requirements as "safety nets" and to achieve herd immunity. The rationales against requirements include low parental acceptance of HPV vaccine, the financial burden on educational systems and health departments, and the possibility for alternatives to increase vaccine uptake. Many challenges to HPV vaccine requirements are addressable, and we conclude with recommendations on how to approach these challenges. PMID- 27552265 TI - US Food Industry Progress During the National Salt Reduction Initiative: 2009 2014. AB - OBJECTIVES: To assess the US packaged food industry's progress from 2009 to 2014, when the National Salt Reduction Initiative had voluntary, category-specific sodium targets with the goal of reducing sodium in packaged and restaurant foods by 25% over 5 years. METHODS: Using the National Salt Reduction Initiative Packaged Food Database, we assessed target achievement and change in sales weighted mean sodium density in top-selling products in 61 food categories in 2009 (n = 6336), 2012 (n = 6898), and 2014 (n = 7396). RESULTS: In 2009, when the targets were established, no categories met National Salt Reduction Initiative 2012 or 2014 targets. By 2014, 26% of categories met 2012 targets and 3% met 2014 targets. From 2009 to 2014, the sales-weighted mean sodium density declined significantly in almost half of all food categories (43%; 26/61 categories). Overall, sales-weighted mean sodium density declined significantly (by 6.8%; P < .001). CONCLUSIONS: National target setting with monitoring through a partnership of local, state, and national health organizations proved feasible, but industry progress was modest. PUBLIC HEALTH IMPLICATIONS: The US Food and Drug Administration's proposed voluntary targets will be an important step in achieving more substantial sodium reductions. PMID- 27552266 TI - One Outcome, Many Trends: Understanding National Data Sources for Road Traffic Fatalities in China. AB - OBJECTIVES: To better understand national data sources and evaluate time trends in road traffic fatalities (RTF) in China. METHODS: We reviewed national sources on RTF data. These included population-based report from the Ministry of Public Security (MPS), sample-based estimates from the Ministry of Health (MOH) and the Disease Surveillance Points System (DSP), as well as model-based estimates from the World Health Organization (WHO), and the Global Burden of Disease Study (GBD). RESULTS: All data sources have limitations in coverage, representativeness or overreliance on model specifications. Despite the discrepancies in methodologies and estimates, all sources indicated an increase in RTF before 2005. Since then, MPS and GBD indicated a decrease, DSP showed plateauing, and MOH and WHO suggested increasing fatalities. However, despite any recent decline, RTF remain high. CONCLUSIONS: The divergent trends in RTF across data sets in China implies a challenge to understanding China's experience with addressing RTF. China needs to reconcile data sources and further improve road safety. PMID- 27552267 TI - Impact of the Berkeley Excise Tax on Sugar-Sweetened Beverage Consumption. AB - OBJECTIVES: To evaluate the impact of the excise tax on sugar-sweetened beverage (SSB) consumption in Berkeley, California, which became the first US jurisdiction to implement such a tax ($0.01/oz) in March 2015. METHODS: We used a repeated cross-sectional design to examine changes in pre- to posttax beverage consumption in low-income neighborhoods in Berkeley versus in the comparison cities of Oakland and San Francisco, California. A beverage frequency questionnaire was interviewer administered to 990 participants before the tax and 1689 after the tax (approximately 8 months after the vote and 4 months after implementation) to examine relative changes in consumption. RESULTS: Consumption of SSBs decreased 21% in Berkeley and increased 4% in comparison cities (P = .046). Water consumption increased more in Berkeley (+63%) than in comparison cities (+19%; P < .01). CONCLUSIONS: Berkeley's excise tax reduced SSB consumption in low-income neighborhoods. Evaluating SSB taxes in other cities will improve understanding of their public health benefit and their generalizability. PMID- 27552268 TI - State-Level Voting Patterns and Adolescent Vaccination Coverage in the United States, 2014. AB - OBJECTIVES: To examine state-level associations between voting patterns and adolescent coverage for at least 1 dose of human papillomavirus (HPV), tetanus containing (Tdap), and meningococcal (MCV4) vaccination. METHODS: We classified states as "blue" (Democratic affiliation) or "red" (Republican affiliation) based on the Presidential election results in 2012. We used multivariable models to adjust for potential confounding by sociodemographic and health care access characteristics and vaccination policies. For HPV, separate models were fitted for boys and girls. RESULTS: Adolescent vaccination coverage was significantly higher in blue states than red states for each vaccine (P < .05). The adjusted percent differences between blue and red states were 10.2% for HPV among girls, 24.9% for HPV among boys, 6.2% for tetanus-containing vaccine, and 14.1% for MCV4. CONCLUSIONS: State-level voting patterns are independently and significantly associated with coverage for routinely recommended adolescent vaccines. These differences may reflect population-level differences in cultural norms and social values. PUBLIC HEALTH IMPLICATIONS: Strategies to increase coverage at the individual, community, or structural level should consider local political settings that may facilitate or hinder effectiveness. PMID- 27552269 TI - Job Satisfaction and Expected Turnover Among Federal, State, and Local Public Health Practitioners. AB - OBJECTIVES: To use data on the governmental public health workforce to examine demographics and elucidate drivers of job satisfaction and intent to leave one's organization. METHODS: Using microdata from the 2014 Federal Employee Viewpoint Survey and 2014 Public Health Workforce Interests and Needs Survey, we drew comparisons between federal, state, and local public health staff. We fitted logistic regressions to examine correlates of both job satisfaction and intent to leave one's organization within the coming year. RESULTS: Correlates of job satisfaction included pay satisfaction, organizational support, and employee involvement. Approximately 40% of federal, state, and local staff said they were either considering leaving their organization in the next year or were planning to retire by 2020. CONCLUSIONS: Public health practitioners largely like their jobs, but many are dissatisfied with their pay and are considering working elsewhere. More should be done to understand the determinants of job satisfaction and how to successfully retain high-quality staff. PUBLIC HEALTH IMPLICATIONS: Public health is at a crossroads. Significant turnover is expected in the coming years. Retention efforts should engage staff across all levels of public health. PMID- 27552270 TI - Safety and Health Support for Home Care Workers: The COMPASS Randomized Controlled Trial. AB - OBJECTIVES: To determine the effectiveness of the COMmunity of Practice And Safety Support (COMPASS) Total Worker Health intervention for home care workers. METHODS: We randomized 16 clusters of workers (n = 149) to intervention or usual practice control conditions. The 12-month intervention was scripted and peer-led, and involved education on safety, health, and well-being; goal setting and self monitoring; and structured social support. We collected measures at baseline, 6 months, and 12 months, which included workers' experienced community of practice (i.e., people engaged in a common activity who interact regularly for shared learning and improvement). Implementation occurred during 2013 and 2014 in Oregon. RESULTS: In an intent-to-treat analysis, relative to control, the intervention produced significant and sustained improvements in workers' experienced community of practice. Additional significant improvements included the use of ergonomic tools or techniques for physical work, safety communication with consumer-employers, hazard correction in homes, fruit and vegetable consumption, lost work days because of injury, high-density lipoprotein cholesterol, and grip strength. Consumer-employers' reports of caregiver safety behaviors also significantly improved. CONCLUSIONS: COMPASS was effective for improving home care workers' social resources and simultaneously impacted both safety and health factors. PMID- 27552271 TI - Bullying Victimization and Racial Discrimination Among Australian Children. AB - OBJECTIVES: To compare the prevalence of bullying victimization and racial discrimination by ethnicity. METHODS: We completed a cross-sectional analysis of 3956 children aged 12 to 13 years from wave 5 (2011-2012) of the nationally representative Longitudinal Study of Australian Children. RESULTS: Bullying victimization and racial discrimination were weakly associated and differently patterned by ethnicity. Children from visible minorities reported less bullying victimization but more racial discrimination than did their peers with Australian born parents. Indigenous children reported the highest risk of bullying victimization and racial discrimination. CONCLUSIONS: Peer victimization and racial discrimination each require specific attention as unique childhood stressors. A focus on general bullying victimization alone may miss unique stress exposures experienced by children from stigmatized ethnic backgrounds. PMID- 27552272 TI - Prices for Tobacco and Nontobacco Products in Pharmacies Versus Other Stores: Results From Retail Marketing Surveillance in California and in the United States. AB - OBJECTIVES: To examine disparities in the price of tobacco and nontobacco products in pharmacies compared with other types of stores. METHODS: We recorded the prices of Marlboro, Newport, the cheapest cigarettes, and bottled water in a random sample of licensed tobacco retailers (n = 579) in California in 2014. We collected comparable data from retailers (n = 2603) in school enrollment zones for representative samples of US 8th, 10th, and 12th graders in 2012. Ordinary least squares regressions modeled pretax prices as a function of store type and neighborhood demographics. RESULTS: In both studies, the cheapest cigarettes cost significantly less in pharmacies than other stores; the average estimated difference was $0.47 to $1.19 less in California. We observed similar patterns for premium-brand cigarettes. Conversely, bottled water cost significantly more in pharmacies than elsewhere. Newport cost less in areas with higher proportions of African Americans; other cigarette prices were related to neighborhood income and age. Neighborhood demographics were not related to water prices. CONCLUSIONS: Compared with other stores, pharmacies charged customers less for cigarettes and more for bottled water. State and local policies to promote tobacco-free pharmacies would eliminate an important source of discounted cigarettes. PMID- 27552273 TI - Reproductive Outcomes Following Maternal Exposure to the Events of September 11, 2001, at the World Trade Center, in New York City. AB - OBJECTIVES: To estimate associations between exposure to the events of September 11, 2001, (9/11) and low birth weight (LBW), preterm delivery (PD), and small size for gestational age (SGA). METHODS: We matched birth certificates filed in New York City for singleton births between 9/11 and the end of 2010 to 9/11 related exposure data provided by mothers who were World Trade Center Health Registry enrollees. Generalized estimating equations estimated associations between exposures and LBW, PD, and SGA. RESULTS: Among 3360 births, 5.8% were LBW, 6.5% were PD, and 9% were SGA. Having incurred at least 2 of 4 exposures, having performed rescue or recovery work, and probable 9/11-related posttraumatic stress disorder 2 to 3 years after 9/11 were associated with PD and LBW during the early study period. CONCLUSIONS: Disasters on the magnitude of 9/11 may exert effects on reproductive outcomes for several years. Women who are pregnant during and after a disaster should be closely monitored for physical and psychological sequelae. PUBLIC HEALTH IMPLICATIONS: In utero and maternal disaster exposure may affect birth outcomes. Researchers studying effects of individual disasters should identify commonalities that may inform postdisaster responses to minimize disaster-related adverse birth outcomes. PMID- 27552274 TI - Community Engagement Compared With Technical Assistance to Disseminate Depression Care Among Low-Income, Minority Women: A Randomized Controlled Effectiveness Study. AB - OBJECTIVES: To compare the effectiveness of a (CEP) versus a technical assistance approach (Resources for Services, or RS) to disseminate depression care for low income ethnic minority women. METHODS: We conducted secondary analyses of intervention effects for largely low-income, minority women subsample (n = 595; 45.1% Latino and 45.4% African American) in a matched, clustered, randomized control trial conducted in 2 low-resource communities in Los Angeles, California, between 2010 and 2012. Outcomes assessed included mental health, socioeconomic factors, and service use at 6- and 12-month follow-up. RESULTS: Although we found no intervention difference for depressive symptoms, there were statistically significant effects for mental health quality of life, resiliency, homelessness risk, and financial difficulties at 6 months, as well as missed work days, self efficacy, and care barriers at 12 months favoring CEP relative to RS. CEP increased use of outpatient substance abuse services and faith-based depression visits at 6 months. CONCLUSIONS: Engaging health care and social community programs may offer modest improvements on key functional and socioeconomic outcomes, reduce care barriers, and increase engagement in alternative depression services for low-income, predominantly ethnic minority women. PMID- 27552275 TI - Effective Referral of Low-Income Women at Risk for Hereditary Breast and Ovarian Cancer to Genetic Counseling: A Randomized Delayed Intervention Control Trial. AB - OBJECTIVES: To determine the effectiveness of a statewide telephone service in identifying low-income women at risk for hereditary breast and ovarian cancer and referring them to free genetic counseling. METHODS: From June 2010 through August 2011, eligible callers to California's toll-free breast and cervical cancer telephone service were screened for their family histories of breast and ovarian cancer. High-risk women were identified and called for a baseline survey and randomization to an immediate offer of genetic counseling or a mailed brochure on how to obtain counseling. Clinic records were used to assess receipt of genetic counseling after 2 months. RESULTS: Among 1212 eligible callers, 709 (58.5%) agreed to answer family history questions; 102 (14%) were at high risk (25% Hispanic, 46% White, 10% Black, 16% Asian, 3% of other racial/ethnic backgrounds). Of the high-risk women offered an immediate appointment, 39% received counseling during the intervention period, as compared with 4.5% of those receiving the brochure. CONCLUSIONS: A public health approach to the rare but serious risk of hereditary breast and ovarian cancer can be successful when integrated into the efforts of existing safety net organizations. PMID- 27552276 TI - Stand-Biased Versus Seated Classrooms and Childhood Obesity: A Randomized Experiment in Texas. AB - OBJECTIVES: To measure changes in body mass index (BMI) percentiles among third- and fourth-grade students in stand-biased classrooms and traditional seated classrooms in 3 Texas elementary schools. METHODS: Research staff recorded the height and weight of 380 students in 24 classrooms across the 3 schools at the beginning (2011-2012) and end (2012-2013) of the 2-year study. RESULTS: After adjustment for grade, race/ethnicity, and gender, there was a statistically significant decrease in BMI percentile in the group that used stand-biased desks for 2 consecutive years relative to the group that used standard desks during both years. Mean BMI increased by 0.1 and 0.4 kilograms per meter squared in the treatment and control groups, respectively. The between-group difference in BMI percentile change was 5.24 (SE = 2.50; P = .037). No other covariates had a statistically significant impact on BMI percentile changes. CONCLUSIONS: Changing a classroom to a stand-biased environment had a significant effect on students' BMI percentile, indicating the need to redesign traditional classroom environments. PMID- 27552277 TI - A Traffic-Light Label Intervention and Dietary Choices in College Cafeterias. AB - OBJECTIVES: To examine whether traffic-light labeling and choice architecture interventions improved dietary choices among students at a northeastern US university. METHODS: In 6 cafeterias at Harvard University, in Cambridge, Massachusetts, we implemented a 7-week intervention including traffic-light labeling (red: least nutrient rich; yellow: nutrient neutral; green: most nutrient rich), choice architecture (how choices are presented to consumers), and "healthy-plate" tray stickers. During the 2014-2015 academic year, 2 cafeterias received all interventions, 2 received choice architecture only, and 2 were controls. We analyzed sales for 6 weeks before and 7 weeks during interventions. Using interrupted time-series analyses, we measured changes in red, yellow, and green items served. We collected 1329 surveys to capture perceptions of labeling. RESULTS: Among 2.6 million portions served throughout the study, we found no significant changes in red (-0.8% change/week; P = .2) or green (+1.1% change/week; P = .4) items served at intervention sites compared with controls. In surveys, 58% of students reported using traffic-light labels at least a few times per week, and 73% wanted them to continue. CONCLUSIONS: Although many students reported using traffic-light labels regularly and wanted interventions to continue, cafeteria interventions did not demonstrate clear improvements in dietary quality. PMID- 27552278 TI - Community Response to a Public Health Advertisement. PMID- 27552279 TI - Medication Costs and Adherence of Treatment Before and After the Affordable Care Act: 1999-2015. AB - To examine national changes in rates of cost-related prescription nonadherence (CRN) by age group, we used data from the 1999-2015 Sample Adult and Sample Child National Health Interview Surveys (n = 768 781). In a logistic regression analysis of 2015 data, we identified subgroups at risk for cost-related nonadherence. The proportion of all Americans who did not fill a prescription in the previous 12 months because they could not afford it grew from 1999 to 2009, peaking at 8.3% at the height of the Great Recession and dropping to 5.2% by 2015. CRN among seniors, however, peaked in 2004 at 5.4% and dropped to 3.6% after implementation of Medicare Part D in 2006. CRN is responsive to improved access related to implementation of Medicare Part D and the Affordable Care Act. PMID- 27552280 TI - A Community-Powered, Asset-Based Approach to Intersectoral Urban Health System Planning in Chicago. AB - OBJECTIVES: To describe, and provide a nomenclature and taxonomy for classifying, the economic sectors and functional assets that could be mobilized as partners in an intersectoral health system. METHODS: MAPSCorps (Meaningful, Active, Productive Science in Service to Community) employed local youths to conduct a census of all operating assets (businesses and organizations) on the South Side of Chicago, Illinois, in 2012. We classified assets by primary function into sectors and described asset and sector distribution and density per 100 000 population. We compared empirical findings with the Institute of Medicine's (IOM's) conceptual representation and description of intersectoral health system partners. RESULTS: Fifty-four youths mapped a 62-square-mile region over 6 weeks; we classified 8376 assets into 23 sectors. Sectors with the most assets were food (n = 1214; 230/100 000 population), trade services (n = 1113; 211/100 000), and religious worship (n = 974;185/100 000). Several large, health-relevant sectors (2499 assets) were identified in the region but not specified in the IOM's representation. Governmental public health, central to the IOM concept, had no physical presence in the region. CONCLUSIONS: Local youths identified several thousand assets across a broad diversity of sectors that could partner in an intersectoral health system. Empirically informed iteration of the IOM concept will facilitate local translation and propagation. PMID- 27552281 TI - Working With the Panthers to Transform Health Care for Poor Black Communities. PMID- 27552282 TI - Medical resource utilization and costs among Australian patients with genotype 1 chronic hepatitis C: results of a retrospective observational study. AB - OBJECTIVE: To evaluate medical resource utilization (MRU) and associated costs among Australian patients with genotype 1 chronic hepatitis C (GT1 CHC), including both untreated patients and those receiving treatment with first generation protease inhibitor-based regimens (telaprevir, boceprevir with pegylated interferon and ribavirin). METHODS: Medical records were reviewed for a stratified random sample of GT1 CHC patients first attending two liver clinics between 2011-2013 (principal population; PP), supplemented by all GT1 CHC patients attending one transplant clinic in the same period (transplant population; TP). CHC-related MRU and associated costs are reported for the PP by treatment status (treated/not treated) stratified by baseline fibrosis grade; and for the TP for the pre-transplant, year of transplant and post-transplant periods. RESULTS: A total 1636 patients were screened and 590 patients (36.1%) were included. Comprehensive MRU data were collected for 276 PP patients (F0-1 n = 59, F2 n = 58, F3 n = 53, F4 n = 106; mean follow-up = 17.3 months). Thirty eight (13.8%) were treatment-experienced prior to enrolment; 55 (19.9%) received triple therapy during the study. Data were collected for 112 TP patients (mean follow-up = 29.9 months), 33 (29.5%) received a transplant during the study, and 51 (45.5%) beforehand. The annual direct medical costs, excluding drug costs, were higher among treated PP vs untreated PP (AU$: $1,954 vs $1,202); and year of transplant TP vs pre-/post-transplant TP (AU$: pre-transplant $32,407, transplant $155,138, post-transplant $7,358). LIMITATIONS: To aid interpretation of results, note that only patients with GT1 CHC who are actively managed are included, and MRU data were collected specifically from liver outpatient clinics. That said, movement of patients between hospitals is rare, and any uncaptured MRU is expected to be minimal. CONCLUSIONS: CHC-related MRU increases substantially with disease severity. These real-world MRU data for GT1 CHC will be valuable in assessing the impact of new hepatitis C treatments. PMID- 27552283 TI - Genome-Wide Association Study in Wheat Identifies Resistance to the Cereal Cyst Nematode Heterodera filipjevi. AB - The cyst nematode Heterodera filipjevi is a plant parasite causing substantial yield loss in wheat. Resistant cultivars are the preferred method of controlling cyst nematodes. Association mapping is a powerful approach to detect associations between phenotypic variation and genetic polymorphisms; in this way favorable traits such as resistance to pathogens can be located. Therefore, a genome-wide association study of 161 winter wheat accessions was performed with a 90K iSelect single nucleotide polymorphism (SNP) chip. Population structure analysis grouped into two major subgroups and first principal component accounted 6.16% for phenotypic diversity. The genome-wide linkage disequilibrium across wheat was 3 cM. Eleven quantitative trait loci (QTLs) on chromosomes 1AL, 2AS, 2BL, 3AL, 3BL, 4AS, 4AL, 5BL, and 7BL were identified using a mixed linear model false discovery rate of P < 0.01 that explained 43% of total genetic variation. This is the first report of QTLs conferring resistance to H. filipjevi in wheat. Eight QTLs on chromosomes 1AL, 2AS, 2BL, 3AL, 4AL, and 5BL were linked to putative genes known to be involved in plant-pathogen interactions. Two other QTLs on 3BL and one QTL on 7BL linked to putative genes known to be involved in abiotic stress. PMID- 27552284 TI - Inhaled corticosteroids for cystic fibrosis. AB - BACKGROUND: Reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of taking regular inhaled corticosteroids, compared to not taking them, in children and adults with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.Date of most recent search of the Group's Trials Register: 15 August 2016. SELECTION CRITERIA: Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas. MAIN RESULTS: The searches identified 34 citations, of which 26 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 506 people with cystic fibrosis aged between six and 55 years. One was a withdrawal trial in individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information. Many of the risk of bias judgements were unclear due to a lack of available information. Only two trials specified how participants were randomised and less than half of the included trials gave details on how allocation was concealed. Trials were generally judged to have a low risk of bias from blinding, except for two which were open label or did not use a placebo. There were some concerns that a number of trials had not been published in peer reviewed journals, but the risk of bias from this was unclear. Inclusion criteria varied between trials, as did type and duration of treatment and timing of outcome assessments. Objective measures of airway function were reported in most trials but were often incomplete. Significant benefit has not been conclusively demonstrated. Four trials systematically documented adverse effects and growth was significantly affected in one study using high doses. AUTHORS' CONCLUSIONS: Evidence from these trials is insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial. PMID- 27552285 TI - Ambient Gas-Particle Partitioning of Tracers for Biogenic Oxidation. AB - Exchange of atmospheric organic compounds between gas and particle phases is important in the production and chemistry of particle-phase mass but is poorly understood due to a lack of simultaneous measurements in both phases of individual compounds. Measurements of particle- and gas-phase organic compounds are reported here for the southeastern United States and central Amazonia. Polyols formed from isoprene oxidation contribute 8% and 15% on average to particle-phase organic mass at these sites but are also observed to have substantial gas-phase concentrations contrary to many models that treat these compounds as nonvolatile. The results of the present study show that the gas particle partitioning of approximately 100 known and newly observed oxidation products is not well explained by environmental factors (e.g., temperature). Compounds having high vapor pressures have higher particle fractions than expected from absorptive equilibrium partitioning models. These observations support the conclusion that many commonly measured biogenic oxidation products may be bound in low-volatility mass (e.g., accretion products, inorganic-organic adducts) that decomposes to individual compounds on analysis. However, the nature and extent of any such bonding remains uncertain. Similar conclusions are reach for both study locations, and average particle fractions for a given compound are consistent within ~25% across measurement sites. PMID- 27552287 TI - Mineralization of Calcium Carbonate on Multifunctional Peptide Assembly Acting as Mineral Source Supplier and Template. AB - Crystal phase and morphology of biominerals may be precisely regulated by controlled nucleation and selective crystal growth through biomineralization on organic templates such as a protein. We herein propose new control factors of selective crystal growth by the biomineralization process. In this study, a designed beta-sheet Ac-VHVEVS-CONH2 peptide was used as a multifunctional template that acted as mineral source supplier and having crystal phase control ability of calcium carbonate (CaCO3) during a self-supplied mineralization. The peptides formed three-dimensional nanofiber networks composed of assembled bilayer beta-sheets. The assembly hydrolyzed urea molecules to one carbonate anion and two ammonium cations owing to a charge relay effect between His and Ser residues under mild conditions. CaCO3 was selectively mineralized on the peptide assembly using the generated carbonate anions on the template. Morphology of the obtained CaCO3 was fiber-like structure, similar to that of the peptide template. The mineralized CaCO3 on the peptide template had aragonite phase. This implies that CaCO3 nuclei, generated using the carbonate anions produced by the hydrolysis of urea on the surface of the peptide assembly, preferentially grew into aragonite phase, the growth axis of which aligned parallel to the direction of the beta-sheet fiber axis. PMID- 27552286 TI - FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein. AB - Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, 5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG). Indeed, FABP1 bound ECs with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA-containing ECs, FABP1 inhibitors, EC uptake/hydrolysis inhibitors, and phytocannabinoids and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists. The physiological impact was examined with liver from wild-type (WT) versus FABP1 gene-ablated (LKO) male mice. As shown by liquid chromatography and mass spectrometry, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD and DAGL) or a decreased level of EC degradative enzyme (FAAH) but correlated with complete loss of FABP1, a decreased level of SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and a decreased level of degradative enzymes (NAAA and MAGL). These data indicated that FABP1 not only is the most prominent endocannabinoid and cannabinoid binding protein but also impacts hepatic endocannabinoid levels. PMID- 27552288 TI - Site-Directed Chemical Mutations on Abzymes: Large Rate Accelerations in the Catalysis by Exchanging the Functionalized Small Nonprotein Components. AB - Taking advantage of antibody molecules to generate tailor-made binding sites, we propose a new class of protein modifications, termed as "site-directed chemical mutation." In this modification, chemically synthesized catalytic components with a variety of steric and electronic properties can be noncovalently and nongenetically incorporated into specific sites in antibody molecules to induce enzymatic activity. Two catalytic antibodies, 25E2 and 27C1, possess antigen combining sites which bind catalytic components and act as apoproteins in catalytic reactions. By simply exchanging these components, antibodies 25E2 and 27C1 can catalyze a wide range of chemical transformations including acyl transfer, beta-elimination, aldol, and decarboxylation reactions. Although both antibodies were generated with the same hapten, phosphonate diester 1, they showed different catalytic activity. When phenylacetic acid 4 was used as the catalytic component, 25E2 efficiently catalyzed the elimination reaction of beta haloketone 2, whereas 27C1 showed no catalytic activity. In this work, we focused on the beta-elimination reaction and examined the site-directed chemical mutation of 27C1 to induce activity and elucidate the catalytic mechanism. Molecular models showed that the cationic guanidyl group of ArgH52 in 27C1 makes a hydrogen bond with the P?O oxygen in the hapten. This suggested that during beta elimination, ArgH52 of 27C1 would form a salt bridge with the carboxylate of 4, thus destroying reactivity. Therefore, we utilized site-directed chemical mutation to change the charge properties of the catalytic components. When amine components 7-10 were used, 27C1 efficiently catalyzed the beta-elimination reaction. It is noteworthy that chemical mutation with secondary amine 8 provided extremely high activity, with a rate acceleration [(kcat/Km 2)/kuncat] of 1 000 000. This catalytic activity likely arises from the proximity effect, plus general-base catalysis associated the electrostatic interactions. In 27C1, the cationic guanidyl group of ArgH52 is spatially close to the nitrogen of the amine components. In this microenvironment, the intrinsic pKa of the amine is perturbed and shifts to a lower pKa, which efficiently abstracts the alpha-proton during the reaction. This mechanism is consistent with the observed kinetic isotope effect (E2 or E1cB mechanism). Thus, site-directed chemical mutation provides a better understanding of enzyme functions and opens new avenues in biocatalyst research. PMID- 27552289 TI - Nanostructure-Induced Distortion in Single-Emitter Microscopy. AB - Single-emitter microscopy has emerged as a promising method of imaging nanostructures with nanoscale resolution. This technique uses the centroid position of an emitter's far-field radiation pattern to infer its position to a precision that is far below the diffraction limit. However, nanostructures composed of high-dielectric materials such as noble metals can distort the far field radiation pattern. Previous work has shown that these distortions can significantly degrade the imaging of the local density of states in metallic nanowires using polarization-resolved imaging. But unlike nanowires, nanoparticles do not have a well-defined axis of symmetry, which makes polarization-resolved imaging difficult to apply. Nanoparticles also exhibit a more complex range of distortions, because in addition to introducing a high dielectric surface, they also act as efficient scatterers. Thus, the distortion effects of nanoparticles in single-emitter microscopy remains poorly understood. Here we demonstrate that metallic nanoparticles can significantly distort the accuracy of single-emitter imaging at distances exceeding 300 nm. We use a single quantum dot to probe both the magnitude and the direction of the metallic nanoparticle-induced imaging distortion and show that the diffraction spot of the quantum dot can shift by more than 35 nm. The centroid position of the emitter generally shifts away from the nanoparticle position, which is in contradiction to the conventional wisdom that the nanoparticle is a scattering object that will pull in the diffraction spot of the emitter toward its center. These results suggest that dielectric distortion of the emission pattern dominates over scattering. We also show that by monitoring the distortion of the quantum dot diffraction spot we can obtain high-resolution spatial images of the nanoparticle, providing a new method for performing highly precise, subdiffraction spatial imaging. These results provide a better understanding of the complex near-field coupling between emitters and nanostructures and open up new opportunities to perform super-resolution microscopy with higher accuracy. PMID- 27552290 TI - Spectral-Domain Optical Coherence Tomography Findings in Cavernous Hemangioma of the Optic Disk. PMID- 27552291 TI - VIGABATRIN TOXICITY IN INFANCY IS ASSOCIATED WITH RETINAL DEFECT IN ADOLESCENCE: A Prospective Observational Study. AB - PURPOSE: The purpose was to determine whether vigabatrin (VGB) (Sabril) attributed retinal toxicity defined by electroretinogram in early childhood is associated with visual system defect in adolescents after discontinuation of VGB. METHODS: This prospective cross-sectional study included 24 children previously treated with VGB and monitored in early childhood by electroretinogram for VGB attributed retinal defects. Ten had been diagnosed with VGB-attributed retinal defect (Group I) and 14 had no VGB-attributed retinal defect (Group II). Outcome measures were extent of monocular visual fields using Goldmann kinetic perimetry and RNFL thickness at the optic nerve head, using optical coherence tomography. RESULTS: Of those able to complete testing (6 eyes Group I and 16 eyes Group II), Goldmann results revealed results of visual field loss in Group I and not in Group II. The optical coherence tomography results demonstrated attenuation of the RNFL in all 6 eyes of Group I participants and in only 1 eye of 10 Group II participants. Optical coherence tomography data were nonoverlapping between Group 1 and Group II eyes. CONCLUSION: The VGB-attributed retinal toxicity identified by means of electroretinogram in infancy was associated with visual field loss and RNFL attenuation of the retinal nerve when tested in adolescence. PMID- 27552293 TI - Extraocular Technique of Intrascleral Intraocular Lens Fixation Using a Pair of the Shaft-Bended 27-Gauge Needles. PMID- 27552296 TI - High prevalence of anti-hepatitis E virus antibodies in outpatients with chronic liver disease in a university medical center in Germany. AB - AIM/OBJECTIVES/BACKGROUND: Hepatitis E virus (HEV) is an emerging disease in developed countries. HEV seroprevalence ranges from 3.2 to 10% in Europe, but is higher in endemic areas such as southern France. In Germany, an increasing incidence of HEV infections has been reported recently. Risk factors for the acquisition of HEV are incompletely understood. METHODS: We screened 295 consecutive patients with chronic liver disease attending the outpatient department at Charite University Hospital for HEV seroprevalence. Epidemiological characteristics were analyzed and patients were questioned for risk factors using a standardized questionnaire. A total of 78 patients without known liver disease were also tested for HEV IgG. RESULTS: Out of 295 screened patients, 62 tested positive for HEV-IgG. Overall, 50% of the HEV-positive patients were women and 23.8% had underlying liver cirrhosis. HEV-positive patients were older than HEV negative patients (mean age 56 vs. 48.6 years). Seroprevalence increased with age from 13% in patients 30-39 years of age to 36.4% in patients 70-79 years of age. Of the total, 46.7% of HEV-IgG-positive patients had contact with domestic animals and 38.3% had received blood transfusions. A total of 50% of the HEV-IgG positive patients had regularly consumed uncooked meat and 45% had regularly consumed wild game or wild boar, which was significantly more frequent than in HEV-IgG-negative patients. CONCLUSION: HEV-IgG seroprevalence was 21% in a cohort of patients with chronic liver disease and 24.4% in a cohort of patients without known liver disease. The higher seroprevalence found among elderly patients suggests a lifetime accumulation of risk of exposure to HEV. The results from this study imply that regular testing should be performed for HEV in developed countries in case of liver disease of unknown etiology. PMID- 27552297 TI - Molecular Dynamics Study on the Photothermal Actuation of a Glassy Photoresponsive Polymer Reinforced with Gold Nanoparticles with Size Effect. AB - We investigated the optical and thermal actuation behavior of densely cross linked photoresponsive polymer (PRP) and polymer nanocomposites containing gold nanoparticles (PRP/Au) using all-atom molecular dynamics (MD) simulations. The modeled molecular structures contain a large number of photoreactive mesogens with linear orientation. Flexible side chains are interconnected through covalent bonds under periodic boundary conditions. A switchable dihedral potential was applied on a diazene moiety to describe the photochemical trans-to-cis isomerization. To quantify the photoinduced molecular reorientation and its effect on the macroscopic actuation of the neat PRP and PRP/Au materials, we characterized the photostrain and other material properties including elastic stiffness and thermal stability according to the photoisomerization ratio of the reactive groups. We particularly examined the effect of nanoparticle size on the photothermal actuation by varying the diameter of the nanofiller (10-20 A) under the same volume fraction of 1.62%. The results indicated that the insertion of the gold nanoparticles enlarges the photostrain of the material while enhancing its mechanical stiffness and thermal stability. When the diameter of the nanoparticle reaches a size similar to or smaller than the length of the mesogen, the interfacial energy between the nanofiller and the surrounding polymer matrix does not significantly affect the alignment of the mesogens, but rather the adsorption energy at the interface generates a stable interphase layer. Hence, these improvements were more effective as the size of the gold nanoparticle decreased. The present findings suggest a wider analysis of the nanofiller reinforced PRP composites and could be a guide for the mechanical design of the PRP actuator system. PMID- 27552292 TI - GEOGRAPHIC ATROPHY: Semantic Considerations and Literature Review. AB - PURPOSE: There is a lack of agreement regarding the types of lesions and clinical conditions that should be included in the term "geographic atrophy." Varied and conflicting views prevail throughout the literature and are currently used by retinal experts and other health care professionals. METHODS: We reviewed the nominal definition of the term "geographic atrophy" and conducted a search of the ophthalmologic literature focusing on preceding terminologies and the first citations of the term "geographic atrophy" secondary to age-related macular degeneration. RESULTS: According to the nominal definition, the term "geography" stands for a detailed description of the surface features of a specific region, indicating its relative position. However, it does not necessarily imply that the borders of the region must be sharply demarcated or related to any anatomical structures. The term "geographical areas of atrophy" was initially cited in the 1960s in the ophthalmologic literature in the context of uveitic eye disease and shortly thereafter also for the description of variants of "senile macular degeneration." However, no direct explanation could be found in the literature as to why the terms "geographical" and "geographic" were chosen. Presumably the terms were used as the atrophic regions resembled the map of a continent or well defined country borders on thematic geographical maps. With the evolution of the terminology, the commonly used adjunct "of the retinal pigment epithelium" was frequently omitted and solely the term "geographic atrophy" prevailed for the nonexudative late-stage of age-related macular degeneration itself. Along with the quantification of atrophic areas, based on different imaging modalities and the use of both manual and semiautomated approaches, various and inconsistent definitions for the minimal lesion diameter or size of atrophic lesions have also emerged. CONCLUSION: Reconsideration of the application of the term "geographic atrophy" in the context of age-related macular degeneration seems to be prudent given ongoing advances in multimodal retinal imaging technology with identification of various phenotypic characteristics, and the observation of atrophy development in eyes under antiangiogenic therapy. PMID- 27552298 TI - Give as I give: Adult influence on children's giving in two cultures. AB - Adult influence on children's altruistic behavior may differ between cultural communities. We used an experimental approach to assess the influence of adult models on children's altruistic giving in a city in the United States and rural villages in India. Children between 3 and 8 years of age were tested with their parents in the United States (n=163) and India (n=154). Parents modeled either a generous or stingy donation; children then performed a similar task in private. Children in both communities were influenced by the stingy model, but only children in India increased their giving after viewing a generous model. The model's influence also increased with age in India. Results of a questionnaire revealed that parents in both communities believed that children learned sharing behavior from them. We consider these results in light of differences between these societies, including different socialization goals, cultural values, and content biases that may affect altruistic giving. PMID- 27552299 TI - A developmental investigation of the first-letter advantage. AB - Skilled adult readers identify the first letter in a string of random consonants better than letters at any other position, and this advantage for the initial position is not seen with strings of symbols or familiar shapes. Here we examined the developmental trajectory of this first-letter advantage by testing children in Grades 1 to 5 of primary education in a target-in-string identification paradigm. Strings of five letters or five simple shapes were briefly presented, and children were asked to identify a target letter/shape at one of the five possible positions. Children responded by choosing between the target and an alternative that was a neighboring letter/shape (e.g., TPFMR-M vs. F at position 4). The serial position function linking accuracy to position-in-string was found to be affected by reading ability differently for letter stimuli compared with shape stimuli, and this was found to be almost entirely driven by differences in performance in identifying targets at the first position in strings. Here, accuracy increased more rapidly for letter stimuli than for shape stimuli as reading ability increased. This developmental pattern, plus the fact that letter strings were composed of random consonants and the task minimized the involvement of verbal recoding, allows us to exclude an explanation of the first-letter advantage in terms of serial reading strategies or phonological decoding. The findings suggest that the first-letter advantage is a function of, and a marker for, increasingly efficient orthographic processing. PMID- 27552300 TI - DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands. AB - AIM: To identify regions of aberrant DNA methylation in acute lymphoblastic leukemia (ALL) cells of different subtypes on a genome-wide scale. MATERIALS & METHODS: Whole-genome bisulfite sequencing (WGBS) was used to determine the DNA methylation levels in cells from four pediatric ALL patients of different subtypes. The findings were confirmed by 450k DNA methylation arrays in a large patient set. RESULTS: Compared with mature B or T cells WGBS detected on average 82,000 differentially methylated regions per patient. Differentially methylated regions are enriched to CpG poor regions, active enhancers and transcriptional start sites. We also identified approximately 8000 CpG islands with variable intermediate DNA methylation that seems to occur as a result of stochastic de novo methylation. CONCLUSION: WGBS provides an unbiased view and novel insights into the DNA methylome of ALL cells. PMID- 27552301 TI - High-Yield Synthesis of Hollow Octahedral Silver Nanocages with Controllable Pack Density and Their High-Performance Sers Application. AB - Nanoparticle-assembled octahedral Ag nanocages with sharp edges have been successfully synthesized through a Cu2 O-based template-assisted strategy. In the reaction system, Ag nanoparticles can be self-assembled on the surface of Cu2 O octahedrons, which is accomplished by the reduction of Ag+ by NaBH4 in the presence of sodium citrate as a capping agent. The hollow octahedral Ag nanocages are obtained after removing the inner Cu2 O cores with acetic acid. According to the scanning electron microscopy (SEM) and transmission electron microscopy characterization, the Ag nanocages are weaved by small nanoparticles, the rough surfaces are bestrewed with pores and sharp edges. It is found that the pack density of Ag nanoparticles strongly affects the surface enhanced Raman scattering (SERS) activities. The as-prepared 1.05-Ag cages with optimal pack density have suitable interparticle distance and suitable size of pores, which significantly enhance SERS signals. The SERS signals of rhodamine 6G (R6G) molecules can be detected at an ultralow concentration of 10-14 m when 1.05-Ag cages are used as substrates. In addition to sensitivity, 1.05-Ag cages also exhibit good reproducibility. It is expected that the ultrahigh sensitivity will endow the Ag nanocages to become a promising candidate as high-performance SERS based chemical sensor. PMID- 27552302 TI - Donor-Acceptor Distance Sampling Enhances the Performance of "Better than Nature" Nicotinamide Coenzyme Biomimetics. AB - Understanding the mechanisms of enzymatic hydride transfer with nicotinamide coenzyme biomimetics (NCBs) is critical to enhancing the performance of nicotinamide coenzyme-dependent biocatalysts. Here the temperature dependence of kinetic isotope effects (KIEs) for hydride transfer between "better than nature" NCBs and several ene reductase biocatalysts is used to indicate transfer by quantum mechanical tunneling. A strong correlation between rate constants and temperature dependence of the KIE (DeltaDeltaH(?)) for H/D transfer implies that faster reactions with NCBs are associated with enhanced donor-acceptor distance sampling. Our analysis provides the first mechanistic insight into how NCBs can outperform their natural counterparts and emphasizes the need to optimize donor acceptor distance sampling to obtain high catalytic performance from H-transfer enzymes. PMID- 27552304 TI - Emergence of antimicrobial resistance among Acinetobacter species: a global threat. AB - PURPOSE OF REVIEW: Bacteria within the genus Acinetobacter [principally Acinetobacter baumannii-calcoaceticus complex (ABC)] are Gram-negative coccobacilli that may cause serious nosocomial infections (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds) as well as community-acquired infections (often skin/soft tissue infections in the context of trauma). Within the past two decades, Acinetobacter spp. have been responsible for an increasing number of infections in intensive care units (ICUs) globally. Treatment of Acinetobacter infections is difficult, as Acinetobacter spp. are intrinsically resistant to multiple antimicrobial agents, and have a remarkable ability to acquire new resistance determinants via multiple mechanisms. RECENT FINDINGS: Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC. Global spread of multidrug resistant (MDR) A. baumannii strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; this spread is amplified by excessive use of antibiotics. Many isolates are resistant to all antimicrobials except colistin (polymyxin E), and some infections are untreatable with existing antimicrobial agents. SUMMARY: Antimicrobial resistance poses a serious threat to control infections due to ABC. Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the consequences and spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes. PMID- 27552303 TI - Factors impacting cerebrospinal fluid leak rates in endoscopic sellar surgery. AB - BACKGROUND: In patients undergoing transnasal endoscopic sellar surgery, an analysis of risk factors and predictors of intraoperative and postoperative cerebrospinal fluid leak (CSF) would provide important prognostic information. METHODS: A retrospective review of patients undergoing endoscopic sellar surgery for pituitary adenomas or craniopharyngiomas between 2002 and 2014 at 7 international centers was performed. Demographic, comorbidity, and tumor characteristics were evaluated to determine the associations between intraoperative and postoperative CSF leaks. Correlations between reconstructive and CSF diversion techniques were associated with postoperative CSF leak rates. Odds ratios (OR) were identified using a multivariate logistic regression model. RESULTS: Data were collected on 1108 pituitary adenomas and 53 craniopharyngiomas. Overall, 30.1% of patients had an intraoperative leak and 5.9% had a postoperative leak. Preoperative factors associated with increased intraoperative leaks were mild liver disease, craniopharyngioma, and extension into the anterior cranial fossa. In patients with intraoperative CSF leaks, postoperative leaks occurred in 10.3%, with a higher postoperative leak rate in craniopharyngiomas (20.8% vs 5.1% in pituitary adenomas). Once an intraoperative leak occurred, craniopharyngioma (OR = 4.255, p = 0.010) and higher body mass index (BMI) predicted postoperative leak (OR = 1.055, p = 0.010). In patients with an intraoperative leak, the use of septal flaps reduced the occurrence of postoperative leak (OR = 0.431, p = 0.027). Rigid reconstruction and CSF diversion techniques did not impact postoperative leak rates. CONCLUSION: Intraoperative CSF leaks can occur during endoscopic sellar surgery, especially in larger tumors or craniopharyngiomas. Once an intraoperative leak occurs, risk factors for postoperative leaks include craniopharyngiomas and higher BMI. Use of septal flaps decreases this risk. PMID- 27552305 TI - Role of lipoproteins and proprotein convertase subtilisin/kexin type 9 in endotoxin clearance in sepsis. AB - PURPOSE OF REVIEW: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a recent high-impact cardiovascular intervention aimed at reducing low-density lipoprotein (LDL) cholesterol levels. Notably, pathogen lipids are also carried in lipoprotein particles and are cleared by hepatocyte LDL receptors. Therefore, the role of PCSK9 in sepsis is reviewed. RECENT FINDINGS: Endogenous PCSK9 decreases clearance of LDL cholesterol by decreasing the number of LDL receptors on hepatocytes. Similarly, PCSK9 decreases clearance of pathogen lipids, such as endotoxin, carried in LDL. Pathogen lipids, such as lipopolysaccharide (LPS) from gram-negative organisms or lipoteichoic acid from gram-positive organisms, are carried in high-density lipoprotein, LDL, and very low-density lipoprotein particles. Transfer proteins that handle pathogen lipids (e.g., LPS binding protein) are homologous to transfer proteins that handle cholesterol (e.g., phospholipid transfer protein, cholesterol ester transfer protein). Reduction in PCSK9 function results in increased LPS clearance, a decreased inflammatory response, and improved clinical outcomes in mice. PCSK9 inhibition improves survival in septic mice. Similarly, humans who carry loss-of function variants of the PCSK9 gene have increased survival in sepsis. SUMMARY: PCSK9 inhibition may be a useful strategy to increase pathogen lipid clearance in the treatment of patients with sepsis. PMID- 27552306 TI - Porphysome nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model: a pilot study. AB - Local disease control is a major challenge in pancreatic cancer treatment, because surgical resection of the primary tumor is only possible in a minority of patients and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for focal ablation of pancreatic tumors, this approach remains underinvestigated. Using photothermal sensitizers in combination with laser light irradiation for PTT can result in more efficient conversion of light energy to heat and improved spatial confinement of thermal destruction to the tumor. Porphysomes are self-assembled nanoparticles composed mainly of pyropheophorbide-conjugated phospholipids, enabling the packing of ~80,000 porphyrin photosensitizers per particle. The high-density porphyrin loading imparts enhanced photonic properties and enables high-payload tumor delivery. A patient-derived orthotopic pancreas xenograft model was used to evaluate the feasibility of porphysome-enhanced PTT for pancreatic cancer. Biodistribution and tumor accumulation were evaluated using fluorescence intensity measurements from homogenized tissues and imaging of excised organs. Tumor surface temperature was recorded using IR optical imaging during light irradiation to monitor treatment progress. Histological analyses were conducted to determine the extent of PTT thermal damage. These studies may provide insight into the influence of heat-sink effect on thermal therapy dosimetry for well perfused pancreatic tumors. PMID- 27552307 TI - Evaluating the effect of local pH on fluorescence emissions from oral bacteria of the genus Prevotella. AB - A number of anaerobic oral bacteria, notably Prevotellaceae, exhibit red fluorescence when excited by short-wavelength visible light due to their accumulation of porphyrins, particularly protoporphyrin IX. pH affects the fluorescence of abiotic preparations of porphyrins due to transformations in speciation between monomers, higher aggregates, and dimers. To elucidate whether the porphyrin speciation phenomenon could be manifested within a microbiological system, suspensions of Prevotella intermedia and Prevotella nigrescens were examined by fluorescence spectrophotometry while being titrated against NaOH. The initial pH of the samples was <6, which was then raised toward the maximum found within a diseased periodontal pocket, being ~pH 8.7. The intensity of the fluorescence emissions increased between 600 and 650 nm with increasing pH. Peak fluorescence emissions occurred at 635+/-1 nm with a second emission peak developing with increasing pH at 622 nm. A linear relationship was demonstrated between pH and the log10 ratio of 635:622 nm excitation fluorescence intensities. These findings suggest that the pH range found within the oral cavity could affect the fluorescence of oral bacteria in vivo, which may in turn have connotations for any clinical diagnoses that may be inferred from dental plaque fluorescence. PMID- 27552308 TI - Laser-triggered release of encapsulated molecules from polylactic-co-glycolic acid microcapsules. AB - The controlled release of encapsulated molecules from a microcapsule is a promising method of targeted drug delivery. Laser-triggered methods for the release of encapsulated molecules have the advantage of spatial and temporal controllability. In this study, we demonstrated the release of encapsulated molecules from biodegradable polymer-based microcapsules using near-infrared femtosecond laser pulses. The polylactic-co-glycolic acid microcapsules encapsulating fluorescein isothiocyanate-dextran molecules were fabricated using a dual-coaxial nozzle system. Irradiation of femtosecond laser pulses enhanced the release of the molecules from the microcapsules, which was accompanied by a decrease in the residual ratio of the microcapsules. The laser-induced modification of the surface of the shell of the microcapsules indicated the potential for sustained release as well as burst release. PMID- 27552309 TI - Comparison of contourlet transform and gray level co-occurrence matrix for analyzing cell-scattered patterns. AB - Distribution of scattered image patterns hinges on morphological and optical characteristics of cells. This paper applied a numerical method to simulate scattered images of real cell morphologies, which were reconstructed from confocal image stacks dyed by fluorescent stains. Two approaches, contourlet transform (CT) and gray level co-occurrence matrix (GLCM), were then used to analyze the simulated scattered images. The results showed that features extracted using GLCM contained more information than those extracted using CT. Higher classification accuracy could be achieved with a single GLCM parameter than CT and GLCM could achieve higher accuracy with fewer parameters than CT when using multiple parameters. Meanwhile, GLCM requires less computational cost. Thus, GLCM is more suitable and efficient than CT for the analysis of cell scattered images. PMID- 27552310 TI - Table top surface plasmon resonance measurement system for efficient urea biosensing using ZnO thin film matrix. AB - The present report addresses the application of surface plasmon resonance (SPR) phenomenon for urea sensing. The former promises a high sensitivity, label-free detection, and real-time information by monitoring the refractive index change at the metal-dielectric interface. In the present report, a highly sensitive urea biosensor has been developed by integrating a ZnO thin film matrix with the SPR technique. Kretschmann configuration has been used to excite the surface plasmon (SP) modes at the ZnO-metal (gold) interface using an indigeneously developed table top SPR measurement setup. Urease (Urs), the urea-specific enzyme, has been immobilized on the surface of ZnO thin film by physical adsorption technique. The SPR reflectance curves were recorded for the prism/Au/ZnO/Urs system in angular interrogation mode with phosphate-buffered saline (PBS) solution as the liquid media. The SPR resonance angle is found to be shifted toward a lower angle from 49.1 to 42.0 deg with an increase in the urea concentration (0 to 300 mg/dl) in the PBS solution. The developed sensor (prism/Au/ZnO/Urs) is found to be highly sensitive [sensitivity=0.039 deg/(mg/dl) or 203 deg/RIU] with detection accuracy of 0.045(deg)(-1). PMID- 27552311 TI - Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study. AB - Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates ( ? ). A macroscopic model was adopted to evaluate using calculated reacted singlet oxygen concentration ( [ O 2 1 ] rx ) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma tumors, as singlet oxygen is the primary cytotoxic species responsible for cell death in type II PDT. Using a combination of fluences (50, 135, 200, and 250 ?? J / cm 2 ) and ? (50, 75, and 150 ?? mW / cm 2 ), tumor regrowth rate, k , was determined for each condition. A tumor cure index, CI = 1 ? k / k control , was calculated based on the k between PDT-treated groups and that of the control, Available on the SPIE Digital Library. PMID- 27552312 TI - Comparison of the efficacy of 308-nm excimer lamp monotherapy with topical tacrolimus or clobetasol 17-propionate combination therapies in localized vitiligo. AB - BACKGROUND: In recent years, excimer light treatments have come to the fore in localized vitiligo because of their high efficacy and safety. OBJECTIVE: We aimed to evaluate the efficacy of 308-nm excimer lamp as a monotherapy and its combination with tacrolimus 0.1% or clobetasol 17-propionate 0.05% ointment in localized vitiligo. METHODS: We performed a retrospective study including a total of 82 patients who were treated with excimer lamp monotherapy (EL group) (n = 30), excimer lamp + topical tacrolimus (EL + T group) (n = 29), or excimer lamp + topical clobetasol 17-propionate (EL + CS group) (n = 23). We used digital morphometric analysis for the evaluation of repigmentation. RESULTS: Median healing rate after 24 sessions was significantly higher in EL + T group (69%) than EL (42.5%) and EL + CS (44%) groups (P = 0.008 and P = 0.032). There were not any patients with face lesions in EL + CS group, so when these patients were excluded, EL + T and EL + CS groups had higher healing rates than EL group (P = 0.037 and P = 0.043). It was confirmed that combination with tacrolimus was superior to clobetasol-17 propionate (P = 0.048) with multivariate regression analysis. CONCLUSION: We noted that 308-nm excimer lamp therapy was efficacious; adding topical tacrolimus or topical clobetasol-17 propionate could increase response to treatment. PMID- 27552313 TI - Prevalence and Visual Outcomes of Cataract Surgery in Rural South India: A Cross Sectional Study. AB - PURPOSE: To determine the prevalence of cataract surgery and postoperative vision related outcomes, especially with respect to sex, socioeconomic status (SES) and site of first contact with eye care, in a rural area of South India. METHODS: In a population-based cross-sectional survey of 5530 individuals aged 50 years or older from 10 villages selected by cluster sampling, individuals who had undergone cataract surgery in one or both eyes were identified. Consenting participants were administered a questionnaire, underwent vision assessment and ophthalmic examination. Outcomes were classified as good if visual acuity of the operated eye was 6/18 or better, fair if worse than 6/18 but better than or equal to 6/60, and poor if worse than 6/60. RESULTS: Prevalence of cataract surgery in this age group (771 persons) was 13.9% (95% confidence interval, CI, 13.0-14.9%). In the 1112 eyes of 749 persons studied, at presentation, 53.1% (95% CI 50.1 56.1%) of operated eyes had good, 38.1% (95% CI 35.2-41.0%) had fair, and 8.8% (95% CI 7.1-10.5%) had poor outcomes. With pinhole, 75.2% (95% CI 72.6-77.8%) had good, 17.2% (95% CI 14.9-19.5%) had fair, and 7.4% (95% CI 5.8-9.0%) had poor outcomes. In 76.3% of eyes with fair and poor presenting outcomes we detected an avoidable cause for the suboptimal visual acuity. Place of surgery and duration since surgery of 3 years or more were risk factors for blindness, while SES, sex and site of first eye care contact were not. CONCLUSION: The high prevalence of avoidable causes of visual impairment in this rural setting indicates the scope for preventive strategies. PMID- 27552314 TI - Global Mental Health in Our Own Backyard: An Unaccompanied Immigrant Child's Migration From El Salvador to New York City. AB - There has been a recent surge in the number of children migrating to the United States without a parent. Despite their vulnerability to extreme adversity at every stage of their migration process, little is known about the psychosocial context and mental health needs of unaccompanied children. This article presents a case study of a 16-year-old Salvadoran boy who participated in a larger, mixed methods study on the psychosocial context, psychological presentation, and mental health service utilization of unaccompanied children living in New York pending their immigration cases. After the presentation of the case, different models for understanding the experiences and needs of unaccompanied children are discussed. PMID- 27552315 TI - Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine. AB - Cigarette smoke is a complex mixture of toxic chemicals, including nicotine, carbon monoxide, and several recognized carcinogens and mutagens. Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear. The aim of this study was to elucidate the effect of nicotine on the expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in endometrial stromal cells. Expression levels of PR, ER, and VEGF in human endometrial stromal primary cells treated with nicotine (0, 10-11, 10-8, and 10-6 MUM) for 24 h were measured by quantitative real-time PCR. MTT assay demonstrated that nicotine decreased cell viability in a dose-dependent manner. Real-time PCR data showed that despite decrease in ER expression in the nicotine-treated groups compared with the control, nicotine exerted an increased inhibitory effect on PR expression compared to that on ER expression. VEGF mRNA expression in nicotine treated endometrial stromal cells was increased. The results from this study provide novel evidence for inhibitory effects of nicotine on steroid hormones receptor expression in human primary endometrial cells. Also, our data suggest that nicotine might have angiogenesis effects on these cells. PMID- 27552317 TI - Labeling viral envelope lipids with quantum dots by harnessing the biotinylated lipid-self-inserted cellular membrane. AB - Highly efficient labeling of viruses with quantum dots (QDs) is the prerequisite for the long-term tracking of virus invasion at the single virus level to reveal mechanisms of virus infection. As one of the structural components of viruses, viral envelope lipids are hard to be labeled with QDs due to the lack of efficient methods to modify viral envelope lipids. Moreover, it is still a challenge to maintain the intactness and infectivity of labeled viruses. Herein, a mild method has been developed to label viral envelope lipids with QDs by harnessing the biotinylated lipid-self-inserted cellular membrane. Biotinylated lipids can spontaneously insert in cellular membranes of host cells during culture and then be naturally assembled on progeny Pseudorabies virus (PrV) via propagation. The biotinylated PrV can be labeled with streptavidin-conjugated QDs, with a labeling efficiency of ~90%. Such a strategy to label lipids with QDs can retain the intactness and infectivity of labeled viruses to the largest extent, facilitating the study of mechanisms of virus infection at the single virus level. PMID- 27552316 TI - Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. AB - Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(ethylene glycol) tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also have significant potentials in engineering large-scale vascularized tissue constructs towards applications in organ transplantation and repair. PMID- 27552318 TI - Multifunctional magnetic nanowires: A novel breakthrough for ultrasensitive detection and isolation of rare cancer cells from non-metastatic early breast cancer patients using small volumes of blood. AB - Circulating tumor cells (CTCs) are recognized as promising biomarkers for diagnosis and indication of the prognosis of several epithelial cancers. However, at present, CTC monitoring is available only for advanced-stage patients rather than for those at an early stage of cancer. This is because of the extraordinary rarity of CTCs and the limited sensitivity of current methods. Herein, we report the development of multifunctional magnetic nanowires for the efficient isolation and detection of CTCs from the blood of patients, especially those with non metastatic early-stage cancer. The nanowires, which are equipped with a high density of magnetic nanoparticles and five different types of antibodies (Ab mixture_mPpyNWs), offer a significant improvement in cell-isolation efficiency, even from very small amounts of blood (250 MUL-1 mL). Notably, CTCs were isolated and identified in 29 out of 29 patients (100%) with non-metastatic early breast cancer, indicating that this procedure allowed detection of CTCs with greater accuracy, sensitivity, and specificity. In addition, we demonstrated in situ "naked eye" identification of the captured cancer cells via a simple colorimetric immunoassay. Our results show that antibody-functionalized magnetic nanowires offer great potential for a broad range of practical clinical applications, including early detection, diagnosis, and treatment of cancer. PMID- 27552319 TI - Gold nanostars for efficient in vitro and in vivo real-time SERS detection and drug delivery via plasmonic-tunable Raman/FTIR imaging. AB - The application of plasmonic-enhanced Raman imaging of cancer cells and drug delivery is gaining momentum. Here, we propose a new theranostic strategy based on an efficient plasmonic-tunable Raman/Fourier transform infrared (FTIR) spectroscopy imaging, to simultaneously evaluate the anticancer drug scattering cellular imaging and the Raman scattering molecular vibration signals in living cells. This technique allows to monitoring the drug release throughout the cell cycle and in vivo biodistribution and biocompatibility with low dose drug therapy (200 MUg/mL) and low toxicity effect. This system can directly track in real-time the delivery and release of an anticancer drug (mitoxantrone, MTX) from gold nanostars in single living cells and in mice (healthy and lung cancer mice models), revealing a strong accumulation in the heart of healthy mice 5 min after administration and infiltration in the tumor site of lung cancer mice 5 h after systemic injection. This in vivo SERS detection method holds a great promise for application in image-guided cancer chemotherapy or as a nonspecific anti inflammatory therapy for patients with cardiovascular diseases or chronic heart failure. PMID- 27552320 TI - Graphene quantum dots conjugated neuroprotective peptide improve learning and memory capability. AB - Alzheimer disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence extracellular neuritic plaques and with a large number of neurons lost. In this paper, we design a new nanomaterial, graphene quantum dots (GQDs) conjugated neuroprotective peptide glycine-proline-glutamate (GQDG) and administer it to APP/PS1 transgenic mice. The in vitro assays including ThT and CD proved that GQDs and GQDG could inhibit the aggregation of Abeta1-42 fibrils. Morris water maze was performed to exanimate learning and memory capacity of APP/PS1 transgenic mice. The surface area of Abeta plaque deposits reduced in the GQDG group compared to the Tg Ctrl groups. Furthermore, newly generated neuronal precursor cell and neuron were test by immunohistochemical. Besides, neurons were impregnated by DiI using gene gun to show dendritic spine. Results indicated enhancement of learning and memory capacity and increased amounts of dendritic spine were observed. Inflammation factors and amyloid-beta (Abeta) were tested with suspension array and ELISA, respectively. Several pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-6, IL-33, IL-17alpha, MIP-1beta and TNF-alpha) had decreased in GQDG group compared with Control group. Reversely, anti-inflammatory cytokines (IL-4, IL-10) had increased in GQDG group compared with Control group. Thus, we demonstrate that the GQDG is a promising drug in treatment of neurodegenerative diseases such as AD. PMID- 27552321 TI - Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection. AB - The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technology. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepared by incubating 100 nm gold nanoparticles in a solution containing an optimized concentration of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphological semblance to natural viral particles under nanoparticle tracking analysis and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture. PMID- 27552323 TI - Biotransport of Algal Toxins to Riparian Food Webs. AB - The occurrence of harmful algal blooms has resulted in growing worldwide concern about threats to aquatic life and human health. Microcystin (MC), a cyanotoxin, is the most widely reported algal toxin in freshwaters. Prior studies have documented its presence in aquatic food webs including commercially important fish and shellfish. In this paper we present the first evidence that algal toxins propagate into riparian food webs. We show that MC is present in emerging aquatic insects (Hexagenia mayflies) from the James River Estuary and their consumers (Tetragnathidae spiders and Prothonotary Warblers, Protonotaria citrea). MC levels in Prothonotary Warblers varied by age class, with nestlings having the highest levels. At the site where nestlings received a higher proportion of aquatic prey (i.e., mayflies) in their diet, we observed higher MC concentrations in liver tissue and fecal matter. Warbler body condition and growth rate were not related to liver MC levels, suggesting that aquatic prey may provide dietary benefits that offset potential deleterious effects of the toxin. This study provides evidence that threats posed by algal toxins extend beyond the aquatic environments in which blooms occur. PMID- 27552324 TI - A Proposal for a Genome Similarity-Based Taxonomy for Plant-Pathogenic Bacteria that Is Sufficiently Precise to Reflect Phylogeny, Host Range, and Outbreak Affiliation Applied to Pseudomonas syringae sensu lato as a Proof of Concept. AB - Taxonomy of plant pathogenic bacteria is challenging because pathogens of different crops often belong to the same named species but current taxonomy does not provide names for bacteria below the subspecies level. The introduction of the host range-based pathovar system in the 1980s provided a temporary solution to this problem but has many limitations. The affordability of genome sequencing now provides the opportunity for developing a new genome-based taxonomic framework. We already proposed to name individual bacterial isolates based on pairwise genome similarity. Here, we expand on this idea and propose to use genome similarity-based codes, which we now call life identification numbers (LINs), to describe and name bacterial taxa. Using 93 genomes of Pseudomonas syringae sensu lato, LINs were compared with a P. syringae genome tree whereby the assigned LINs were found to be informative of a majority of phylogenetic relationships. LINs also reflected host range and outbreak association for strains of P. syringae pathovar actinidiae, a pathovar for which many genome sequences are available. We conclude that LINs could provide the basis for a new taxonomic framework to address the shortcomings of the current pathovar system and to complement the current taxonomic system of bacteria in general. PMID- 27552322 TI - How does gatekeeper training improve suicide prevention for elderly people in nursing homes? A controlled study in 24 centres. AB - BACKGROUND: The death rate due to suicide in elderly people is particularly high. As part of suicide selective prevention measures for at-risk populations, the WHO recommends training "gatekeepers". METHODS: In order to assess the impact of gatekeeper training for members of staff, we carried out a controlled quasi experimental study over the course of one year, comparing 12 nursing homes where at least 30% of the staff had undergone gatekeeper training with 12 nursing homes without trained staff. We collected data about the residents considered to be suicidal, their management further to being identified, as well as measures taken at nursing home level to prevent suicide. RESULTS: The two nursing home groups did not present significantly different characteristics. In the nursing homes with trained staff, the staff were deemed to be better prepared to approach suicidal individuals. The detection of suicidal residents relied more on the whole staff and less on the psychologist alone when compared to nursing homes without trained staff. A significantly larger number of measures were taken to manage suicidal residents in the trained nursing homes. Suicidal residents were more frequently referred to the psychologist. Trained nursing homes put in place significantly more suicide prevention measures at an institutional level. CONCLUSIONS: Having trained gatekeepers has an impact not only for the trained individuals but also for the whole institution where they work, both in terms of managing suicidal residents and routine suicide prevention measures. PMID- 27552326 TI - Jackhammer Esophagus in High-Resolution Manometry Era. PMID- 27552325 TI - Genome-Wide Association Study of Spot Form of Net Blotch Resistance in the Upper Midwest Barley Breeding Programs. AB - Pyrenophora teres f. maculata, the causal agent of spot form of net blotch (SFNB), is an emerging pathogen of barley in the United States and Australia. Compared with net form of net blotch (NFNB), less is known in the U.S. Upper Midwest barley breeding programs about host resistance and quantitative trait loci (QTL) associated with SFNB in breeding lines. The main objective of this study was to identify QTL associated with SFNB resistance in the Upper Midwest two-rowed and six-rowed barley breeding programs using a genome-wide association study approach. A total of 376 breeding lines of barley were evaluated for SFNB resistance at the seedling stage in the greenhouse in Fargo in 2009. The lines were genotyped with 3,072 single nucleotide polymorphism (SNP) markers. Phenotypic evaluation showed a wide range of variability among populations from the four breeding programs and the two barley-row types. The two-rowed barley lines were more susceptible to SFNB than the six-rowed lines. Continuous distributions of SFNB severity indicate the quantitative nature of SFNB resistance. The mixed linear model (MLM) analysis, which included both population structure and kinship matrices, was used to identify significant SNP-SFNB associations. Principal component analysis was used to control false marker-trait association. The linkage disequilibrium (LD) estimates varied among chromosomes (10 to 20 cM). The MLM analysis identified 10 potential QTL in barley: SFNB-2H-8 10, SFNB-2H-38.03, SFNB-3H-58.64, SFNB-3H-78.53, SFNB-3H-91.88, SFNB-3H-117.1, SFNB-5H-155.3, SFNB-6H-5.4, SFNB-6H-33.74, and SFNB-7H-34.82. Among them, four QTL (SFNB-2H-8-10, SFNB-2H-38.03 SFNB-3H-78.53, and SFNB-3H-117.1) have not previously been published. Identification of SFNB resistant lines and QTL associated with SFNB resistance in this study will be useful in the development of barley genotypes with better SFNB resistance. PMID- 27552327 TI - Results of the FIT-based National Colorectal Cancer Screening Program in Slovenia. AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies in the western world. OBJECTIVE: We aimed to assess the first round of fecal immunochemical test (FIT)-based National CRC screening program (NCSP). METHODS: In the NCSP conducted in Slovenia, a FIT and colonoscopy for those tested positive was used. The NCSP central unit sent 536,709 invitations to Slovenian residents age 50 to 69 years old between 2009 and 2011. The adherence rate was 56.9% (303,343 participants). FIT was positive in 6.2% (15,310) of the participants (men, 7.8%; women, 5.0%; P<0.01). A total of 13,919 unsedated colonoscopies were performed with the cecal intubation rate of 97.8%. RESULTS: The overall adenoma detection rate was 51.3% [95% confidence interval (CI), 50.5% 52.1%] of which 61.0% (95% CI, 59.9%-62.1%) was in men, and 39.1% (95% CI, 37.8% 40.3%) in women (P<0.01). The mean number of adenoma per positive colonoscopy was 1.94 (95% CI, 1.90-1.97). Adenoma, advanced adenoma, or cancer were found in 7732 (55.5%) colonoscopies. A total of 862 (6.2%) CRC cases were found. Only 161 (18.7%) carcinomas were situated in the right colon. A total of 597 (70.2%) patients with cancer were in the early clinical stages (N, negative; 194 22.8%) of all cancers were cured with only endoscopic resection. CONCLUSIONS: In the NCSP, CRC was found in 6.2% of those participants attending colonoscopy, with 81.3% of carcinomas found in the left colon. A localized clinical stage was found in 70.2% participants. In 22.8% of CRC patients, cancer was cured with endoscopic resection only. PMID- 27552328 TI - Clinical Features of Chronic Hepatitis B in Treatment-naive Asian Patients With Positive HBeAg and Coexisting Precore and/or Basal Core Promoter Mutations. AB - BACKGROUND: Precore or/and basal core promoter (PC/BCP) mutations are frequently detected in hepatitis B e antigen (HBeAg)-negative patients, but little is known about their clinical significance in HBeAg-positive patients. AIM: To characterize and report the clinical features of treatment-naive chronic hepatitis B patients who are HBeAg positive and harbor PC and/or BCP mutations. PATIENTS AND METHODS: Consecutive treatment-naive patients with chronic hepatitis B between 2004 and 2014 were enrolled. Clinical characteristics were compared based on the stratification of HBeAg status and the presence of PC/BCP mutations. In addition, subset analysis in HBeAg-positive cohort was performed to compare clinical features of patients with and without PC/BCP mutations RESULTS:: Of the 267 patients enrolled from 3 centers, 177 were HBeAg positive and 90 HBeAg negative. When compared with HBeAg-negative patients, HBeAg-positive patients were significantly younger in mean age (37.93 vs. 44.40; P<0.001), had higher levels of median ALT (51 vs. 30.5 U/mL; P<0.001), higher levels of mean HBV DNA (7.50+/-1.48 vs. 5.10+/-1.44 log10 copies/mL; P<0.001), and lower frequency of detectable PC/BCP mutations (60.45% vs. 93.33%; P<0.001), but had significantly higher frequency of BCP when mutations were detected (37.85% vs. 22.22%; P=0.013). Among HBeAg-positive patients, when compared with patients with wild type, those with PC/BCP mutations were significantly older (30.63 vs. 42.71; P<0.001), had higher median ALT levels (29.5 vs. 73 U/mL; P<0.001), but there was no significant association with mean HBV DNA levels (7.96 vs. 7.20 log10 copies/mL; P=0.865) or HBV genotype (P=1.000). In the multivariate analysis, only age and ALT were independently associated with PC/BCP mutations in HBeAg-positive patients, but there was no association with HBV genotype or DNA. CONCLUSIONS: PC/BCP mutants were frequent (up to 60%) in treatment-naive HBeAg-positive patients and were associated with distinct clinical characteristics when compared with patients with wild type or HBeAg negative. Future large studies are needed to substantiate the long-term clinical outcomes when PC/BCP mutations are detected in HBeAg-positive patients as it may impact the natural history or treatment response in such patients. PMID- 27552330 TI - Endoscopic Management of Esophagopleural Fistula. PMID- 27552329 TI - EndoClot Polysaccharide Hemostatic System in Nonvariceal Gastrointestinal Bleeding: Results of a Prospective Multicenter Observational Pilot Study. AB - BACKGROUND AND STUDY AIMS: Hemostatic powders have been introduced to improve the management of gastrointestinal (GI) bleeding and to extend the variety of tools available for emergency endoscopy. The aim of the present pilot study was to evaluate the indication profiles and the short-term outcome of EndoClot. PATIENTS, MATERIALS AND METHODS: In a prospective observational pilot study patients with acute nonvariceal GI bleeding were included. Primary or secondary application of EndoClot was assessed. Hemoglobin, prothrombine time and platelets were documented before and after hemostasis. The efficacy of EndoClot was assessed 72 hours and 1 week after application. RESULTS: Seventy patients with acute GI bleeding were recruited into the study. Eighty-three percent (58/70) of the patients had upper and 17% (12/70) had lower GI bleeding. In the upper GI tract treatment success was achieved in 64% (30/47, 95% confidence interval, 50% 76%) after primary use and in all patients, when used after established techniques had failed (95% confidence interval, 70%-100%). In lower GI bleeding hemostasis was achieved in 83% of cases (10/12, 95% confidence interval 54%-97%). Rebleeding occurred in 11% (8/70), in 10% EndoClot served as a bridge to surgery (7/70). CONCLUSIONS: EndoClot expanded the therapeutic options in the management of GI bleeding. It was applicable as a monotherapy or in combination with other techniques from oozing bleeding type or lower. It was most effective in diffuse or extensive bleeding activity or when access to the bleeding vessel was difficult. EndoClot can be applied as a bridge to surgery when classical methods of hemostasis have failed. PMID- 27552331 TI - Gastrointestinal Dysmotility in the Elderly. AB - The number of persons 60 years and older has increased 3-fold between 1950 and 2000. Aging alone does not greatly impact the gastrointestinal (GI) tract. Digestive dysfunction, including esophageal reflux, achalasia, dysphagia, dyspepsia, delayed gastric emptying, constipation, fecal incontinence, and fecal impaction, is a result of the highly prevalent comorbid conditions and the medications with which those conditions are treated. A multidisciplinary approach with the expertise of a geriatrician, gastroenterologist, neurologist, speech pathologist, and physical therapist ensures a comprehensive functional and neurological assessment of the older patient. Radiographic and endoscopic evaluation may be warranted in the evaluation of the symptomatic older patient with consideration given to the risks and benefits of the test being used. Treatment of the digestive dysfunction is aimed at improving health-related quality of life if cure cannot be achieved. Promotion of healthy aging, treatment of comorbid conditions, and avoidance of polypharmacy may prevent some of these digestive disorders. The age-related changes in GI motility, clinical presentation of GI dysmotility, and therapeutic principles in the symptomatic older patient are reviewed here. PMID- 27552332 TI - Increased Cell Adhesion Molecules, PECAM-1, ICAM-3, or VCAM-1, Predict Increased Risk for Flare in Patients With Quiescent Inflammatory Bowel Disease. AB - GOALS AND BACKGROUND: Predicting the risk of flare-ups for patients with inflammatory bowel disease (IBD) is difficult. Alterations in gut endothelial regulation of mucosal immune homeostasis might be early events leading to flares in IBD. Cell adhesion molecules (CAMs), in particular, are important in maintaining endothelial integrity and regulating the migration of leukocytes into the gut. STUDY: We evaluated the mRNA expression of various tight junction proteins, with an emphasis on CAMs, in 40 patients with IBD in clinical remission. Patients were retrospectively assessed at 6, 12, and 24 months after baseline colonoscopy, and at the end of all available follow-up (maximum 65 mo), for flare events to determine whether baseline mRNA expression was associated with subsequent flares. RESULTS: At all follow-up points, the baseline expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), ICAM-3, and VCAM-1 was significantly higher in patients who flared than in those who did not (2.4 fold elevation, P=0.012 for PECAM-1; 1.9-fold increased, P=0.03 for ICAM-3; and 1.4-fold increased, P=0.02 for VCAM-1). PECAM-1 and ICAM-3 expression was significantly increased in patients who flared as early as 6 months after baseline colonoscopy. In contrast, there were no significant differences between patients with and without flares in baseline expression of other CAMs (ESAM, ICAM 1, ICAM-2, E-selectin, P-selectin, and MadCAM1). CONCLUSIONS: Increased expression of PECAM-1, ICAM-3, and VCAM-1 in colonic biopsies from patients with IBD in clinical remission is associated with subsequent flares. This suggests that increases in the expression of these proteins may be early events that lead to flares in patients with IBD. PMID- 27552333 TI - Can neurologic examination predict pathophysiology of ulnar neuropathy at the elbow? AB - OBJECTIVE: To explore the utility of neurologic examination to predict the pathophysiology of ulnar nerve lesions in patients with ulnar neuropathies at the elbow (UNE). METHODS: We prospectively recruited consecutive patients with suspected UNE. Four blinded investigators took a history and performed neurologic, electrodiagnostic (EDx) and ultrasonographic (US) examinations. In patients with axonal UNE, conduction block and conduction slowing, the pathophysiologies of UNE and neurologic examination findings were compared. RESULTS: We found significant differences in muscle bulk and strength of the ulnar hand muscles between 96 arms with axonal UNE, 34 with conduction block, and 45 with isolated conduction slowing. Severe muscle atrophy and weakness (0-3/5 on MRC) predicted axonal UNE, and moderate weakness (-4/5 on MRC) with normal muscle bulk predicted UNE with conduction block. Using more restrictive criteria for axonal and conduction block UNE, muscle strength of 4-5/5 on MRC was predictive of isolated conduction slowing. CONCLUSION: Although we found significant differences in patterns of muscle bulk and strength between groups of UNE patients with different UNE pathophysiologies, in the majority of arms, neurologic examination could not reliably predict UNE pathophysiology. SIGNIFICANCE: Results confirm that nerve conduction studies are essential for determination of the pathophysiology of ulnar neuropathy at the elbow. PMID- 27552334 TI - Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI). AB - OBJECTIVE: Approximately 20% of women with a premutation in the FMR1 gene experience primary ovarian insufficiency (POI). We explored diagnostic patterns, frequency of appropriate hormone replacement, obstetric outcomes, fertility treatment, reproductive decisions, and counseling of women with fragile X associated POI (FXPOI). METHODS: Semistructured interviews with 79 women with FXPOI were conducted by a single interviewer. FMR1 cytosine-guanine-guanine repeat size was determined from a blood, saliva, or buccal sample. RESULTS: The median age of POI onset for women in our study was 33 years. Seventy-two percent of the women had an FMR1 cytosine-guanine-guanine repeat length of 80 to 100. Mean length of time from symptom onset to POI diagnosis was 1.12 years, longer in women with a younger age of POI onset and shorter in women who knew they were carriers. After diagnosis, 52% of women never took hormone therapy, started it years after POI diagnosis, or stopped it before 45 years of age. Forty-nine percent of the women had infertility, but 75% had had at least one genetically related child. Obstetric outcomes were similar to the general population. Forty six percent of women had a diagnosis of low bone mineral density or osteoporosis, and an additional 19% had never had a bone density assessment. CONCLUSIONS: Women with FXPOI are at significant risk for delayed POI diagnosis and undertreatment with hormone therapy. Although approximately 50% of women had infertility, most were able to conceive at least one child and had no elevated risk of adverse obstetric outcomes. PMID- 27552335 TI - The miR-449b polymorphism, rs10061133 A>G, is associated with premature ovarian insufficiency. AB - OBJECTIVE: To determine if the miR-449b polymorphism, rs10061133 A>G, is associated with premature ovarian insufficiency (POI) pathogenesis. METHODS: From January 2011 to December 2014, a total of 148 individuals with POI and 225 age matched controls were collected from the Center for Reproductive Medicine, 1st Affiliated Hospital of Anhui Medical University (Hefei, China). Genotyping of miR 449b rs1006113 was performed using matrix-assisted laser desorption ionization time-of-flight-based mass spectrometry. RESULTS: Rs10061133 A>G is a highly conserved SNP locus in the mature area of miR-449b. Association analysis shows that the rs10061133 AA genotype is a risk factor for POI. CONCLUSIONS: Our study provides the first evidence that the miR-449b rs10061133 AA genotype is associated with POI risk. PMID- 27552336 TI - A randomized, double-blind, placebo-controlled phase 2 pilot trial evaluating a novel, vaginal softgel capsule containing solubilized estradiol: Erratum. PMID- 27552337 TI - Monolayers of Poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol) Microparticles Formed by Controlled Self-Assembly with Potential Application as Protein-Repelling Substrates. AB - The kinetics of the self-assembly of poly(styrene/alpha-tert-butoxy-omega vinylbenzyl-polyglycidol) microparticles on poly(allylamine hydrochloride) derivatized silicon/silica substrate was determined by direct AFM imaging and streaming potential (SP) measurements. The kinetic runs acquired under diffusion controlled transport were quantitatively interpreted in terms of the extended random sequential adsorption (RSA) model. This allowed confirmation of a core/shell morphology of the microparticles. The polyglycidol-rich shell of thickness equal to 25 nm exhibited a fuzzy structure that enabled penetration of particles into each other resulting in high coverage inaccessible for ordinary microparticles. The SP measurements interpreted by using the 3D electrokinetic model confirmed this microparticle structure. Additionally, the acid-base characteristics of the microparticle monolayers were determined for a broad pH range. By using the streaming potential measurements, human serum albumin (HSA) adsorption on the microparticle monolayers was investigated under in situ conditions. It was confirmed that the protein adsorption was considerably lower than for the reference case of bare silicon/silica substrate under the same physicochemical conditions. This effect was attributed to the presence of the shell diminishing the protein/microparticle physical interactions. PMID- 27552338 TI - Using Facebook as a platform for self-regulated curriculum evaluation and feedback for medical students. PMID- 27552339 TI - Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. AB - Loss of function mutations in Kelch-like ECH Associated Protein 1 (KEAP1), or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2), are common in non-small cell lung cancer (NSCLC) and associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of ~400 000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to Neh1, the Cap 'N' Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homologue G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs, doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells, as compared to single agents. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation, leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant antitumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC. PMID- 27552340 TI - Symptoms of Depression, Positive Symptoms of Psychosis, and Suicidal Ideation Among Adults Diagnosed With Schizophrenia Within the Clinical Antipsychotic Trials of Intervention Effectiveness. AB - Suicide is among leading causes of death for adults diagnosed with schizophrenia. While symptoms of depression are consistently supported factors involved in suicidal ideation, findings on the role of positive symptoms of psychosis have been mixed with limited understandings of risk. Accordingly, this study aimed to identify the pathways of influence between symptoms of depression, positive symptoms of psychosis (i.e. hallucinations and delusions), and suicidal ideation. Data were obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE; n = 1,460). Suicidal ideation and symptoms of depression were measured by the Calgary Depression Scale (CDRS) and hallucinations and delusions by the Positive and Negative Syndrome Scale (PANSS). The data were analyzed using Structural Equation Modeling (SEM). As symptoms of depression and positive symptoms of psychosis independently increased, on average there were associated increases in suicidal ideation. The present study provides support for the relationship between positive symptoms of psychosis, specifically hallucinations and delusions, and suicidal ideation. Future prospective longitudinal study designs are needed to further increase understandings of the roles that hallucinations, delusions, and additional symptoms of schizophrenia play in both suicidal ideation and attempt to ultimately inform evidence-based interventions aiming to reduce suicidal death. PMID- 27552341 TI - SVANTE - The Swedish Articulation and Nasality Test - Normative data and a minimum standard set for cross-linguistic comparison. AB - Normative language-based data are important for comparing speech performances of clinical groups. The Swedish Articulation and Nasality Test (SVANTE) was developed to enable a detailed speech assessment. This study's aim was to present normative data on articulation and nasality in Swedish speakers. Single word production, sentence repetition and connected speech were collected using SVANTE in 443 individuals. Mean (SD) and prevalences in the groups of 3-, 5-, 7-, 10-, 16- and 19-year-olds were calculated from phonetic transcriptions or ordinal rating. For the 3- and 5-year-olds, a consonant inventory was also determined. The mean percent of oral consonants correct ranged from 77% at age 3 to 99% at age 19. At age 5, a mean of 96% was already reached, and the consonant inventory was established except for /s/, /r/, /c/. The norms on the SVANTE, also including a short version, will be useful in the interpretation of speech outcomes. PMID- 27552342 TI - Effects of Lactobacillus plantarum CCFM0236 on hyperglycaemia and insulin resistance in high-fat and streptozotocin-induced type 2 diabetic mice. AB - AIMS: The aim of this study was to rapidly screen potential hypoglycaemic strain by alpha-glucosidase inhibitory activity in vitro, then explored the antidiabetic effect of Lactobacillus plantarum CCFM0236 in vivo. METHODS AND RESULTS: The cell free supernatant of Lact. plantarum CCFM0236 significantly inhibited alpha glucosidase activity in vitro. Therefore, the effects of Lact. plantarum CCFM0236, with potential hypoglycaemia activity, on insulin resistance and hyperglycaemia were explored in high-fat and streptozotocin-induced type 2 diabetes mice. Oral administration of Lact. plantarum CCFM0236 was found to decrease food intake, blood glucose level, glycosylated haemoglobin level and leptin level. Treatments of Lact. plantarum CCFM0236 also favourably regulated insulin level, AUCglucose , and HOMA-IR index, and increased the activities of glutathione peroxidase and the levels of glutathione, high-density lipoprotein cholesterol and interleukin-10. In addition, Lact. plantarum CCFM0236 reduced levels of malondialdehyde and tumour necrosis factor-alpha and protected pancreas function. CONCLUSIONS: Lactobacillus plantarum CCFM0236 has potential hypoglycaemic ability by ameliorating insulin resistance, antioxidant capacity and systemic inflammation in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The method of alpha-glucosidase inhibitory activity could be effectively used to screen potential hypoglycaemic products and Lact. plantarum CCFM0236 might be a promising therapeutic agent for ameliorating type 2 diabetes. PMID- 27552343 TI - Physiological and biochemical responses of the freshwater green algae Closterium ehrenbergii to the common disinfectant chlorine. AB - Chlorine (Cl2) is widely used as a disinfectant in water treatment plants and for cleaning swimming pools; it is finally discharged into aquatic environments, possibly causing damage to the non-target organisms in the receiving water bodies. Present study evaluated the effects of the biocide Cl2 to the green alga Closterium ehrenbergii (C. ehrenbergii). Growth rate, chlorophyll a levels, carotenoids, chlorophyll autofluorescence, and antioxidant enzymes were monitored up to 72-h after Cl2 exposure. C. ehrenbergii showed dose-dependent decrease in growth rate and cell division after exposure to Cl2. By using cell counts, the median effective concentration (EC50)-72-h was calculated to be 0.071mgL(-1). Cl2 significantly decreased the pigment levels and chlorophyll autofluorescence intensity, indicating that the photosystem was damaged in C. ehrenbergii. In addition, it increased the production of reactive oxygen species (ROS) in the cells. This stressor significantly increased the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase, and glutathione, and affected the physiology of the cells. These results indicate that Cl2 induces oxidative stress in the cellular metabolic process and leads to physiological and biochemical damages in the green algae. Cl2 discharged in industrial effluents and from water treatment plants may cause harmful effects to the C. ehrenbergii a common freshwater microalgae and other non-target organisms. PMID- 27552345 TI - Erratum to: Fatty acid extract from CLA-enriched egg yolks can mediate transcriptome reprogramming of MCF-7 cancer cells to prevent their growth and proliferation. AB - [This corrects the article DOI: 10.1186/s12263-016-0537-z.]. PMID- 27552344 TI - Physical activity and training in sarcoidosis: review and experience-based recommendations. AB - INTRODUCTION: Sarcoidosis is a multisystemic inflammatory disorder with a great variety of symptoms, including fatigue, dyspnea, pain, reduced exercise tolerance and muscle strength. Physical training has the potential to improve exercise capacity and muscle strength, and reduce fatigue. The aim of this review and survey was to present information about the role of physical training in sarcoidosis and offer practical guidelines. AREAS COVERED: A systematic literature review guided an international consensus effort among sarcoidosis experts to establish practice-basic recommendations for the implementation of exercise as treatment for patients with various manifestations of sarcoidosis. International sarcoidosis experts suggested considering physical training in symptomatic patients with sarcoidosis. Expert commentary: There is promising evidence of a positive effect of physical training. Recommendations were based on available data and expert consensus. However, the heterogeneity of these patients will require modification and program adjustment of the standard rehabilitation format for e.g. COPD or interstitial lung diseases. An optimal training program (types of exercise, intensities, frequency, duration) still needs to be defined to optimize training adjustments, especially reduction of fatigue. Further randomized controlled trials are needed to consolidate these findings and optimize the comprehensive care of sarcoidosis patients. PMID- 27552346 TI - Long-distance peptide signaling essential for nutrient homeostasis in plants. AB - Organ-to-organ communication is indispensable for higher organisms to maintain homeostasis over their entire life. Recent findings have uncovered that plants, like animals, mediate organ-to-organ communication by long-distance signaling through the vascular system. In particular, xylem-mobile secreted peptides have attracted much attention as root-to-shoot long-distance signaling molecules in response to fluctuating environmental nutrient status. Several leguminous CLE peptides induced by rhizobial inoculation act as 'satiety' signals in long distance negative feedback of nodule formation. By contrast, Arabidopsis CEP family peptides induced by local nitrogen (N)-starvation behave as systemic 'hunger' signals to promote compensatory N acquisition in other parts of the roots. Xylem sap peptidomics also implies the presence of still uncharacterized long-distance signaling peptides. This review highlights the current understanding of and new insights into the mechanisms and functions of root-to shoot long-distance peptide signaling during environmental responses. PMID- 27552347 TI - Contamination of salmon fillets and processing plants with spoilage bacteria. AB - The processing environment of salmon processing plants represents a potential major source of bacteria causing spoilage of fresh salmon. In this study, we have identified major contamination routes of important spoilage associated species within the genera Pseudomonas, Shewanella and Photobacterium in pre-rigor processing of salmon. Bacterial counts and culture-independent 16S rRNA gene analysis on salmon fillet from seven processing plants showed higher levels of Pseudomonas spp. and Shewanella spp. in industrially processed fillets compared to salmon processed under strict hygienic conditions. Higher levels of Pseudomonas spp. and Shewanella spp. were found on fillets produced early on the production day compared to later processed fillets. The levels of Photobacterium spp. were not dependent on the processing method or time of processing. In follow up studies of two plants, bacterial isolates (n=2101) from the in-plant processing environments (sanitized equipment/machines and seawater) and from salmon collected at different sites in the production were identified by partial 16S rRNA gene sequencing. Pseudomonas spp. dominated in equipment/machines after sanitation with 72 and 91% of samples from the two plants being Pseudomonas positive. The phylogenetic analyses, based on partial 16S rRNA gene sequencing, showed 48 unique sequence profiles of Pseudomonas of which two were dominant. Only six profiles were found on both machines and in fillets in both plants. Shewanella spp. were found on machines after sanitation in the slaughter department while Photobacterium spp. were not detected after sanitation in any parts of the plants. Shewanella spp. and Photobacterium spp. were found on salmon in the slaughter departments. Shewanella was frequently present in seawater tanks used for bleeding/short term storage. In conclusion, this study provides new knowledge on the processing environment as a source of contamination of salmon fillets with Pseudomonas spp. and Shewanella spp., while Photobacterium spp. most likely originate from the live fish and seawater. The study show that strict hygiene during processing is a prerequisite for optimal shelf life of salmon fillets and that about 90% reductions in the initial levels of bacteria on salmon fillets can be obtained using optimal hygienic conditions. PMID- 27552348 TI - Activity of R(+) limonene on the maximum growth rate of fish spoilage organisms and related effects on shelf-life prolongation of fresh gilthead sea bream fillets. AB - R(+)limonene (LMN) is the major aromatic compound in essential oils obtained from oranges, grapefruits, and lemons. The improvement of preservation techniques to reduce the growth and activity of spoilage microorganisms in foods is crucial to increase their shelf life and to reduce the losses due to spoilage. The aim of this work is to evaluate the effect of LMN on the shelf life of fish fillets. Its effectiveness was preliminarily investigated in vitro against 60 strains of Specific Spoilage Organisms (SSOs) and then on gilt-head sea bream fillets stored at 2+/-0.5 degrees C for 15days under vacuum. LMN showed a good inhibitory effect against tested SSOs strains. On gilt-head sea bream fillets, LMN inhibited the growth SSOs effectively, and its use resulted in a shelf-life extension of ca. 6 9days of treated fillets, compared to the control samples. The LMN addition in Sparus aurata fillets giving a distinctive smell and like-lemon taste to fish fillets that resulted pleasant to panellists. Its use contributed to a considerable reduction of fish spoilage given that the fillets treated with LMN were still sensory acceptable after 15days of storage. LMN may be used as an effective antimicrobial system to reduce the microbial growth and to improve the shelf life of fresh gilt-head sea bream fillets. PMID- 27552350 TI - Restoration of Vision After Brain Injury Using Magnet Glasses. AB - Visual impairments are common after traumatic brain injury (TBI) and negatively affect quality of life. We describe a 39-year-old woman with a severe TBI who was evaluated by the inpatient optometry and vision rehabilitation service with findings of complete right homonymous hemianopia and right cranial nerve III palsy with 30-degree right exotropia (eye turn out) and complete right ptosis (eyelid will not open). The 30-degree exotropia advantageously generated 30 degrees of right visual field expansion when the right ptosis was treated with a magnetic levator prosthesis, which restores eyelid opening. Once opened, the patient used visual field expansion derived from a right exotropia to overcome functional impairments caused by right hemianopia. Field expansion improved the patient's wheelchair mobility and reaching tasks during inpatient therapy. This is the first report of visual field expansion by strabismus facilitated by correction of ptosis. Strabismus should be considered for its potential field expansion benefits when homonymous visual deficits are present, before considering patching. A multidisciplinary vision rehabilitation team is well suited to make this determination. PMID- 27552351 TI - Effects of Exercise and Sport in Solid Organ Transplant Recipients: A Review. AB - Solid organ transplantation is the criterion standard treatment for many with end organ failure and can offer a new independence from the burden of disease. However solid organ transplant recipients (SOTRs) remain at high risk of cardiovascular (CV) disease, and poor quality of life and physical functioning. Increasing physical activity and exercise can improve the health of the general population; however, the effects on those with a transplant remain unclear. Intensive exercise and sporting activity has the potential to be beneficial, although there remain concerns particularly around the effects on immune function and the CV system. This review summarizes what is known about the effects of exercise on determinants of health in SOTRs and then collates the available literature investigating the consequences of intensive exercise and sport on the health of SOTR. There is a paucity of high-quality research, with most evidence being case studies or anecdotal; this is understandable given the relatively few numbers of SOTRs who are performing sport and exercise at a high level. However, if suitable evidence-based guidelines are to be formed and SOTRs are to be given reassurances that their activity levels are not detrimental to their transplanted organ and overall health, then more high-quality studies are required. PMID- 27552352 TI - Comparison of the Efficacy of Dry Needling and High-Power Pain Threshold Ultrasound Therapy with Clinical Status and Sonoelastography in Myofascial Pain Syndrome. AB - OBJECTIVE: The aim of this study was to compare the therapeutic efficacy of high power pain threshold (HPPT) ultrasound therapy applied to the trigger points and dry needling (DN) in myofascial pain syndrome. DESIGN: Sixty-one patients were randomly assigned to an HPPT (n = 30) and dry needling (n = 31) groups. The primary outcome measures were the Visual Analog Scale (VAS) and Neck Pain and Disability Scale (NPDS), both at 1 week and 4 weeks after treatment. The secondary outcome measures were the number of painful trigger points, range of the tragus-acromioclavicular joint, the Short Form-36, the Beck Depression Inventory, the Beck Anxiety Inventory, and sonoelastographic tests after a 1-week treatment. RESULTS: More improvement was seen in anxiety in the HPPT group (P < 0.05). However, no significant differences were found between the groups with regard to other parameters (P > 0.05). A decrease in tissue stiffness was only seen in the HPPT group (P < 0.05). Significant posttreatment improvements were seen on all clinical scales in both groups (P < 0.05). After a treatment period of 4 weeks, a significant improvement was also observed on the visual analog scale and NPDS (P < 0.05). CONCLUSIONS: Our study favors the efficacy of both treatment methods in myofascial pain syndrome. Although a significant decrease was shown in tissue stiffness with HPPT, neither of these treatments had an apparent superiority. PMID- 27552353 TI - Occlusion of Tracheostomy Tubes Does Not Alter Pharyngeal Phase Kinematics But Reduces Penetration by Enhancing Pharyngeal Clearance: A Prospective Study in Patients With Neurogenic Dysphagia. AB - OBJECTIVE: Tracheostomy tubes (TT) are often needed in patients with severe neurologic injuries to protect the respiratory system from aspiration. However, TTs alter physiological oral-nasal airflow and are suspected to influence the pattern of pharyngeal swallowing. The aim of this work was to evaluate the effect of TT occlusion on pharyngeal swallowing physiology and to determine penetration aspiration (PA) values of open versus closed TTs in neurogenic dysphagia. DESIGN: Prospective controlled clinical study with 20 tracheotomized patients after unilateral hemispheric stroke. Pharyngeal manometry and flexible endoscopic evaluation of swallowing were performed simultaneously to determine pharyngoesophageal pressure and timing, as well as PA scores with open and occluded TTs. In each condition, patients had to swallow 5 mL of puree 5 times. RESULTS: Pharyngoesophageal pressure amplitudes, duration, and timing of the swallows did not change as a result of the tracheostomy tube status. Penetration aspiration values were significantly lower in the occluded tube condition (P = 0.024). CONCLUSIONS: Airflow and tracheostomy tube status did not influence the physiology of pharyngoesophageal swallowing in patients with neurogenic dysphagia. However, occluded TTs permitted the voluntary clearance of laryngeal residue and resulted in improved PA scores. We recommend performing dysphagia therapy in tracheotomized patients as soon as possible with uncuffed and occluded tubes. PMID- 27552354 TI - Complex and Simple Clinical Reaction Times Are Associated with Gait, Balance, and Major Fall Injury in Older Subjects with Diabetic Peripheral Neuropathy. AB - OBJECTIVE: The aim of this work was to identify relationships between complex and simple clinical measures of reaction time (RTclin) and indicators of balance in older subjects with and without diabetic peripheral neuropathy (DPN). DESIGN: Prospective cohort design. Complex RTclin accuracy, simple RTclin latency, and their ratio were determined using a novel device in 42 subjects (mean +/- SD age, 69.1 +/- 8.3 yrs), 26 with DPN and 16 without. Dependent variables included unipedal stance time (UST), step width variability and range on an uneven surface, and major fall-related injury over 12 months. RESULTS: In the DPN subjects, the ratio of complex RTclin accuracy to simple RTclin latency was strongly associated with longer UST (R/P = 0.653/0.004), and decreased step width variability and range (R/P = -0.696/0.001 and -0.782/<0.001, respectively) on an uneven surface. Additionally, the 2 DPN subjects sustaining major injuries had lower complex RTclin accuracy:simple RTclin latency than those without. CONCLUSIONS: The ratio of complex RTclin accuracy:simple RTclin latency is a potent predictor of UST and frontal plane gait variability in response to perturbations and may predict major fall injury in older subjects with DPN. These short latency neurocognitive measures may compensate for lower limb neuromuscular impairments and provide a more comprehensive understanding of balance and fall risk. PMID- 27552355 TI - A Screening Tool to Identify Spasticity in Need of Treatment. AB - OBJECTIVE: To develop a clinically useful patient-reported screening tool for health care providers to identify patients with spasticity in need of treatment regardless of etiology. DESIGN: Eleven spasticity experts participated in a modified Delphi panel and reviewed and revised 2 iterations of a screening tool designed to identify spasticity symptoms and impact on daily function and sleep. Spasticity expert panelists evaluated items pooled from existing questionnaires to gain consensus on the screening tool content. The study also included cognitive interviews of 20 patients with varying spasticity etiologies to determine if the draft screening tool was understandable and relevant to patients with spasticity. RESULTS: The Delphi panel reached an initial consensus on 21 of 47 items for the screening tool and determined that the tool should have no more than 11 to 15 items and a 1-month recall period for symptom and impact items. After 2 rounds of review, 13 items were selected and modified by the expert panelists. Most patients (n = 16 [80%]) completed the cognitive interview and interpreted the items as intended. CONCLUSIONS: Through the use of a Delphi panel and patient interviews, a 13-item spasticity screening tool was developed that will be practical and easy to use in routine clinical practice. PMID- 27552356 TI - BRCA-1 Gene Expression and Comparative Proteomic Profile of Primordial Follicles from Young and Adult Buffalo (Bubalus bubalis) Ovaries. AB - In our previous study, we demonstrated that the repair efficiency of DNA double strand breaks declines with increasing age in rat primordial follicles. In the present study, we extended our studies to buffalo (Bubalus bubalis) wherein we studied the expression of BRCA-1 related DNA repair genes in primordial follicles of young (12 months-22 months) and adult (72-96 months) buffaloes. The relative expression of selected genes, as determined by RT-PCR, revealed a significant (p < 0.05) decrease in mRNA levels of BRCA1, MRE11, RAD51, ATM, and H2AX in adult primordial follicles as compared to the young. Western blot analysis revealed a significant (p < 0.05) decrease in the expression of phosphorylated protein levels of BRCA1 and H2AX in adult buffalo primordial follicles. The protein expression profile of young and adult buffalo primordial follicles revealed differential expression of proteins involved in mitochondrial function, cell survival and cell metabolism. Similar to reports from aging rodent and human primordial follicles, our findings support the fact that impairment of DNA repair may be an universal mechanism involved in oocyte aging. PMID- 27552357 TI - Catheter-Directed Thrombolysis via Small Saphenous Veins for Treating Acute Deep Venous Thrombosis. AB - BACKGROUND There is little data comparing catheter-directed thrombolysis (CDT) via small saphenous veins vs. systematic thrombolysis on complications and efficacy in acute deep venous thrombosis patients. The aim of our study was to compare the efficacy and safety of CDT via the small saphenous veins with systematic thrombolysis for patients with acute deep venous thrombosis (DVT). MATERIAL AND METHODS Sixty-six patients with acute DVT admitted from June 2012 to December 2013 were divided into 2 groups: 27 patients received systemic thrombolysis (ST group) and 39 patients received CDT via the small saphenous veins (CDT group). The thrombolysis efficiency, limb circumference differences, and complications such as post-thrombotic syndrome (PTS) in the 2 groups were recorded. RESULTS The angiograms demonstrated that all or part of the fresh thrombus was dissolved. There was a significant difference regarding thrombolysis efficiency between the CDT group and ST group (71.26% vs. 48.26%, P=0.001). In both groups the postoperative limb circumference changes were higher compared to the preoperative values. The differences between postoperative limb circumferences on postoperative days 7 and 14 were significantly higher in the CDT group than in the ST group (all P<0.05). The incidence of postoperative PTS in the CDT group (17.9%) was significantly lower in comparison to the ST group (51.85%) during the follow-up (P=0.007). CONCLUSIONS Catheter-directed thrombolysis via the small saphenous veins is an effective, safe, and feasible approach for treating acute deep venous thrombosis. PMID- 27552358 TI - Landscape genetics of a pollinator longhorn beetle [Typocerus v. velutinus (Olivier)] on a continuous habitat surface. AB - Landscape connectivity, the degree to which the landscape structure facilitates or impedes organismal movement and gene flow, is increasingly important to conservationists and land managers. Metrics for describing the undulating shape of continuous habitat surfaces can expand the usefulness of continuous gradient surfaces that describe habitat and predict the flow of organisms and genes. We adopted a landscape gradient model of habitat and used surface metrics of connectivity to model the genetic continuity between populations of the banded longhorn beetle [Typocerus v. velutinus (Olivier)] collected at 17 sites across a fragmentation gradient in Indiana, USA. We tested the hypothesis that greater habitat connectivity facilitates gene flow between beetle populations against a null model of isolation by distance (IBD). We used next-generation sequencing to develop 10 polymorphic microsatellite loci and genotype the individual beetles to assess the population genetic structure. Isolation by distance did not explain the population genetic structure. The surface metrics model of habitat connectivity explained the variance in genetic dissimilarities 30 times better than the IBD model. We conclude that surface metrology of habitat maps is a powerful extension of landscape genetics in heterogeneous landscapes. PMID- 27552359 TI - Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides. AB - beta-Lactam antibiotics allergy is recognized as a public health concern. By covalently binding to serum proteins, penicillins are known to form immunogenic complexes. The latter are recognized and digested by antigen-presenting cells into drug-hapten peptides leading to the immunization of treated persons and IgE mediated hypersensitivity reactions encompassing anaphylaxis. If type I allergic reactions to drugs are often unpredictable, they are known to be dependent on CD4+ T-cells. This fundamental study revisits the chemical basis of the benzylpenicillin (BP) allergy with the aim of identifying immunologically relevant biomimetic benzylpenicilloylated peptides through the analysis of BP conjugated human serum albumin (BP-HSA) profile and the evaluation of the naive CD4+ T-cell responses to candidate BP-HSA-derived peptides. The chemical structures of BP-HSA bioconjugates synthesized in vitro at both physiological and basic pH were investigated by mass spectrometry. From the ten most representative lysine residues grafted by BP-hapten, HSA-bioinspired 15-mer peptide sequences were designed and the potential T-cell epitope profile of each peptide was predicted using two complementary in silico approaches, i.e., HLA class II binding prediction tools from the Immune Epitope Database and Analysis Resource (IEDB) and computational alanine scanning mutagenesis. Twelve structurally diversified benzylpenicilloylated peptides (BP-Ps) were selected and synthesized with the aid of a flexible synthesis pathway using an original benzylpenicilloylated lysine monomer as common precursor. In order to corroborate their predicted "epitope" profile, the naive CD4+ T-cell response specific to BP was evaluated through a coculture approach. To our knowledge, this study showed for the first time the ability of bioinspired peptides structurally stemming from BP-HSA to be recognized by naive CD4+ T-cells thus identifying a pre-existing T cell repertoire for penicillin molecules bound to proteins. It also established a promising model approach expandable to other most frequently used penicillin classes of antibiotics to reveal biomimetic drug-modified antigenic peptides relevant for qualitative and quantitative drug allergy studies. PMID- 27552360 TI - Regio- and Stereoselective Hydrosilylation of Unsymmetrical Alkynes Catalyzed by a Well-Defined, Low-Valent Cobalt Catalyst. AB - Herein, the use of a well-defined low-valent cobalt(I) catalyst [HCo(PMe3)4] capable of performing the highly regio- and stereoselective hydrosilylation of internal alkynes is reported. The reaction can be applied to a variety of hydrosilanes, symmetrical and unsymmetrical alkynes, giving in many cases a single hydrosilylation isomer. Experimental and theoretical studies suggest the key step to be a hydro-cobaltation and that the reaction proceeds through a classical Chalk-Harrod mechanism. PMID- 27552361 TI - RELATIONSHIPS BETWEEN BREAST-FEEDING, CO-SLEEPING, AND SOMATIC COMPLAINTS IN EARLY CHILDHOOD. AB - The central aim of this study was to expand a limited body of knowledge on the complex relationship between breast-feeding, co-sleeping, and somatic complaints in early childhood. An opportunity sample of 98 parents from the general population with children aged 18 to 60 months consented to participate in the study. Each parent completed a series of questionnaires measuring somatic complaints, sleep problems, co-sleeping, breast-feeding, and demographic factors. Findings indicated that co-sleeping was associated with increased somatic complaints and that breast-feeding associated with decreased somatic complaints. Co-sleeping also was found to be associated with an increase in sleep problems. Boys demonstrated significantly higher levels of sleep problems than did girls. These findings highlight the relationship between co-sleeping during early childhood, which could have implications for prevention, treatment, and intervention regarding somatic complaints and sleep problems in early childhood. PMID- 27552362 TI - Older women public sector workers in Ireland: Decisions about retirement timing. AB - Older women workers' decision making around retirement is increasingly important given the increasing involvement of older women in paid employment. This article explores influences on the retirement decision making of older women workers in Ireland. It is based on a case study of 57 interviews with women in the Irish civil service exploring work-life decision making. It finds that retirement choices vary according to initial socioeconomic resources and/or life-course trajectories and are particularly affected by gendered caring norms, employment policy, job tenure, and place in organizational hierarchies. Those women with interrupted careers and low pay have fewer choices around retirement timing. PMID- 27552364 TI - Association between Exposure to Smartphones and Ocular Health in Adolescents. PMID- 27552363 TI - Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer. AB - BACKGROUND: Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. This review is an update of a previously published Cochrane review. OBJECTIVES: To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions, or no treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2015, Issue 8), MEDLINE/PubMed (1949 to September 2015), and EMBASE/Ovid (1980 to September 2015) for potentially relevant articles. In addition, we searched reference lists of relevant articles, conference proceedings of the International Society for Paediatric Oncology (SIOP), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), the International Conference on Long-Term Complications of Treatment of Children & Adolescents for Cancer, and the European Symposium on Late Complications from Childhood Cancer (from 2005 to 2015), and ongoing trial databases (the ISRCTN Register, the National Institutes of Health (NIH) Register, and the trials register of the World Health Organization (WHO); all searched in September 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions, or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments, which another review author checked. We performed analyses according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: In the original version of the review we identified two RCTs; in this update we identified no additional studies. One trial (135 participants) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 participants) compared a two week treatment of phosphocreatine with a control treatment (vitamin C, adenosine triphosphate, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations.The RCT on enalapril showed no statistically significant differences in overall survival, mortality due to heart failure, development of clinical heart failure, and quality of life between treatment and control groups. A post hoc analysis showed a decrease (that is improvement) in one measure of cardiac function (left ventricular end-systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Participants treated with enalapril had a higher risk of dizziness or hypotension (risk ratio 7.17, 95% confidence interval 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function, and adverse events between treatment and control groups. AUTHORS' CONCLUSIONS: Only one trial evaluated the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.Only one trial evaluated the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatments on echocardiographic function and clinical outcomes.We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.High-quality studies should be performed. PMID- 27552365 TI - The suppression of Antarctic bottom water formation by melting ice shelves in Prydz Bay. AB - A fourth production region for the globally important Antarctic bottom water has been attributed to dense shelf water formation in the Cape Darnley Polynya, adjoining Prydz Bay in East Antarctica. Here we show new observations from CTD instrumented elephant seals in 2011-2013 that provide the first complete assessment of dense shelf water formation in Prydz Bay. After a complex evolution involving opposing contributions from three polynyas (positive) and two ice shelves (negative), dense shelf water (salinity 34.65-34.7) is exported through Prydz Channel. This provides a distinct, relatively fresh contribution to Cape Darnley bottom water. Elsewhere, dense water formation is hindered by the freshwater input from the Amery and West Ice Shelves into the Prydz Bay Gyre. This study highlights the susceptibility of Antarctic bottom water to increased freshwater input from the enhanced melting of ice shelves, and ultimately the potential collapse of Antarctic bottom water formation in a warming climate. PMID- 27552366 TI - Use of Antipsychotics During Pregnancy: Pregnant Women Get Sick-Sick Women Get Pregnant. PMID- 27552367 TI - A Highly Reactive Imidazolium-Bridged Dinucleotide Intermediate in Nonenzymatic RNA Primer Extension. AB - Because of its importance for the origin of life, the nonenzymatic copying of RNA templates has been the subject of intense study for several decades. Previous characterizations of template-directed primer extension using 5'-phosphoryl-2 methylimidazole-activated nucleotides (2-MeImpNs) as substrates have assumed a classical in-line nucleophilic substitution mechanism, in which the 3'-hydroxyl of the primer attacks the phosphate of the incoming monomer, displacing the 2 methylimidazole leaving group. However, we have found that the initial rate of primer extension depends on the pH and concentration at which the activated monomer is maintained prior to the primer extension reaction. These and other results suggest an alternative mechanism, in which two monomers react with each other to form an imidazolium-bridged dinucleotide intermediate, which then binds to the template. Subsequent attack of the 3'-hydroxyl of the primer displaces an activated nucleotide as the leaving group and results in extension of the primer by one nucleotide. Analysis of monomer solutions by NMR indicates formation of the proposed imidazolium-bridged dinucleotide in the expected pH-dependent manner. We have used synthetic methods to prepare material that is enriched in this proposed intermediate and show that it is a highly reactive substrate for primer extension. The formation of an imidazolium-bridged dinucleotide intermediate provides a mechanistic interpretation of previously observed catalysis by an activated nucleotide located downstream from the site of primer extension. PMID- 27552368 TI - Assessment of heavy metals accumulation by spontaneous vegetation: Screening for new accumulator plant species grown in Kettara mine-Marrakech, Southern Morocco. AB - The present paper aims to perform a screening of native plants growing in Kettara mine-Marrakech (Southern Morocco) for its phytoremediation. Plants and soil samples were collected and analyzed for Pb, Zn, Cu and Cd concentrations at several sites in the mine. The results showed that the soil in the vicinity of Kettara mine is deficient in major elements and contain toxic levels of metals. Spontaneously growing native plants were botanically identified and then classified into 21 species and 14 families. Significant difference was observed among the average concentrations of four heavy metals (Pb, Zn, Cu and Cd) in plants (p <= 0.05). Six plants of 21 species namely Hammada scoparia (Pomel) Iljin, Hirschfeldia incana (L.) Lagreze-Fossat, Lamarckia aurea (L.) Moench, Calendula algeriensis Boiss. & Reuter, Aizoon hispanicum L. and Melilotus sulcata Desf. were considered as the best-performing specimens due to their high ability to accumulate multiple metals in their shoots and roots without sustaining toxicity. This was confirmed by the transfer factors generally higher than 1. Using the most common criteria to classify the hyperaccumulator plants, these species can be classified as new accumulator plants of many heavy metals and be potentially used as remediation tools of metal-contaminated sites. PMID- 27552369 TI - Electro-response of MoS2 Nanosheets-Based Smart Fluid with Tailorable Electrical Conductivity. AB - The correlation between electrical conductivity and electro-responsive behavior is identified by introducing few-layer molybdenum disulfide (MoS2) nanosheets to electrorheological (ER) fluid. Few-layer MoS2 nanosheets are successfully fabricated, with a high yield of above 60%, using a straightforward method, and applied to an electro-responsive smart fluid. The electrical conductivity of MoS2 is easily tunable by adjusting the annealing temperature because of its semiconducting behavior. From an in-depth study on the conductivity-dependent ER behavior of few-layer MoS2 nanosheets, it can be verified that an optimum value of the electrical conductivity exists for the electro-responsive material, corresponding to the Wagner model. To the best of our knowledge, this is the first report on the potential of a transition-metal dichalcogenide as a candidate material for an ER fluid. This study may provide promising approaches for the performance improvement of electro-responsive smart fluids. PMID- 27552370 TI - Blutgerinnung - ein wichtiges Thema in der Perinatalmedizin. PMID- 27552371 TI - Tumor-specific frequencies and ocular melanoma. AB - Specific kilohertz frequencies in the environment from variable frequency drives on electric motors at a liquid natural gas compressor and storage station on a natural gas pipeline seem to be associated with the development of a very rare cancer, ocular melanoma, at a high school and in individuals living or working in a neighborhood near the plant. Primary neutral-to-earth oscilloscope voltage waveforms and spectra measured near the high school were nearly identical to the ground voltage 2.3 miles away at the gas pipeline. Peak frequencies of 7440 and 19,980 Hz were found at both places. The electric utility practice of using the earth as a conduit for return currents facilitated this exposure. PMID- 27552372 TI - The Development of Representations of Pretend Object Substitutions. AB - Many theories of how pretense is mentally represented have been posited, but none have been effectually empirically tested to date. This research is the first to explore how children and adults mentally process simple pretend actions, specifically pretend object substitutions, and whether this representation changes with age. Preschoolers, older children, and undergraduates heard or read about a variety of pretend object substitutions, and their reaction time to name an image related to the object's real identity, pretend identity, or an unrelated image was measured. To test what is unique to pretense, these reaction times were compared to those from participants who responded to the same images after reading about nonpretend versions of the same actions. Results suggest that preschoolers inhibit reality when representing a pretend action, older children activate an object's real and pretend identities equally, and adults activate the object's real identity more than the pretend one. Implications for current theories of pretense representation are discussed. PMID- 27552373 TI - The role of microRNA in periodontal tissue: A review of the literature. AB - MicroRNAs (miRNAs) bind at the 3'UTR of their target mRNA to induce gene silencing. Through this mechanism, number of biological pathways implicated in developmental, physiological, and pathological processes, have been frequently found to involve miRNA functions. MiRNA functions in bone metabolism have also been reported, especially in association with receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis. Expression of RANKL has been related to several inflammatory mediators, and thus some miRNAs may be implicated in the regulatory mechanism of inflammatory-induced RANKL expression as shown in periodontal resident cells such as gingival fibroblasts or periodontal ligament cells. This review aims to review the current miRNA research relating periodontal tissue and its relevance in periodontal inflammation. In miRNA profiling studies of tissues isolated from individuals with periodontal disease, miR-223 has been consistently identified as a potential candidate miRNA to be further investigated in periodontitis-related processes. Although these studies point to an important role of miRNA-mediated epigenetic changes in tissue inflammation and alveolar bone loss, further investigation is still required to determine the function of miRNAs in the complex processes of periodontal tissue homeostasis and pathogenesis. Knowledge gained from future studies will be beneficial in developing alternative therapeutic approaches, especially ones that use miRNA delivery systems to treat periodontal disease. PMID- 27552374 TI - Immunohistochemical analysis of the gingiva with periodontitis of type I plasminogen deficiency compared to gingiva with gingivitis and periodontitis and healthy gingiva. AB - OBJECTIVE: Type I plasminogen deficiency (Plgdef) is an uncommon chronic inflammation of mucous membranes. Gingival enlargements usually proceed with progressive periodontal destruction and tooth-loss. Plasmin(ogen)-independent enzymatic mechanisms for fibrin clearance have already been discussed in the literature. Our primary objective was to verify, immunohistochemically, the occurrence of different enzymatic factors involved in tissue breakdown of inflamed compared to healthy gingiva. Secondly, we tried to find out, if these patients have a similar microbiological profile to the patients with known gingivitis and periodontitis. MATERIALS AND METHODS: Immunohistochemical analysis of enzymes elastase, plasminogen (plg), cathepsin G, matrix-metalloproteinase (MMP)-3 and MMP-7 and of glycoprotein fibrinogen were performed with gingival tissues from 3 healthy controls, 8 patients with Plgdef and 3 patients with gingivitis and periodontitis. Furthermore, plaque from 5 patients with plasminogen deficiency were also obtained to determine the microbiological profile. RESULTS: Significantly high numbers of elastase positive leukocytes were detected in all samples. Staining for MMP-3 and MMP-7 was seen in samples with gingivitis and periodontitis with a stronger staining in samples with periodontitis by Plgdef. Fibrinogen was detectable in all samples. Staining for plg was stronger in samples with periodontitis than in other samples. Staining for cathepsin G was weak in gingivitis and periodontitis. Subgingival microbial flora showed elevated colony forming units of Prevotella intermedia/nigrescens, Fusobacterium spp., Eikenella corrodens, Porphyromonas gingivalis and viridans streptococci. CONCLUSION: Strong staining of elastase, MMP-3 and MMP-7 and weak staining of plg in Plgdef samples supports the plasmin(ogen) - independent fibrin clearance. Similar subgingival microbiological flora was observed in periodontitis with Plgdef as in other periodontal diseases. Further investigations should determine the exact pathomechanism and focus on effective treatment methods of this entity. PMID- 27552375 TI - Clinical periodontal status and inflammatory cytokines in gestational diabetes mellitus. AB - OBJECTIVES: The aim of the present cross-sectional study was to compare clinical periodontal findings as well as gingival crevicular fluid (GCF) and serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and IL-33 between women with and without gestational diabetes mellitus (GDM). METHODS: Serum and GCF samples were collected, full-mouth recordings comprising plaque index, bleeding on probing and probing depth were performed in 96 females with GDM (cases) and 65 non-diabetic pregnant females (controls). Age, smoking status, pre-pregnancy body mass index, pregnancy outcomes were recorded. Serum and GCF IL 10, IL-33, TNF-alpha levels were determined. RESULTS: The GDM group was significantly older than the control group with an age difference of 3.27 years (mean ages were 32.05 and 28.78 years, respectively) (p<0.0001). Plaque Index (50.0 and 30.0 p=0.005), bleeding on probing (50.0 and 30.0 p=0.003) values were significantly higher in the GDM group. Serum TNF-alpha concentrations were significantly higher in the nonGDM group than the GDM group (p=0.001). GCF IL-10 concentrations and total amounts were significantly higher in the GDM group than the controls (p=0.004 and p<0.0001, respectively). CONCLUSION: Elevated GCF IL-10 levels may be a consequence of higher levels of inflammation as indicated by higher PI and BOP in the GDM group. However, the investigated clinical parameters may not have prominent effects on TNF-alpha and IL-33 levels. These findings provide further support for the importance of periodontal health during pregnancy. PMID- 27552376 TI - The Learning Curve of Transareola Single-site Laparoendoscopic Thyroidectomy: CUSUM Analysis of a Single Surgeon's Experience. AB - BACKGROUND: Transareola single-site laparoendoscopic thyroidectomy (TASSET) is a rapidly advancing minimally invasive procedure. The purpose of this study was to evaluate the learning curve for TASSET. SUBJECTS AND METHODS: Forty-five consecutive patients were prospectively divided into group 1 (initial phase), group 2 (intermediate phase), and group 3 (advanced phase) according to their surgical order (15 patients in each group). The operative time, operative blood loss, duration of hospital stay, postoperative pain, and postoperative complications were compared using phases. RESULTS: Statistically significant differences were observed in the different learning phases, among operative time (P<0.05), operative blood loss (P<0.05), hospital stay (P<0.05), and postoperative pain (P<0.05). The postoperative complication rate was low (3/45). CONCLUSIONS: Learning curve of the TASSET are improved synchronized at different phases and technical indicators. The establishment of operative space take longer time to skilled master. PMID- 27552377 TI - Clinical Significance of Totally Laparoscopic Distal Gastrectomy: A Comparison of Short-term Outcomes Relative to Open and Laparoscopic-assisted Distal Gastrectomy. AB - BACKGROUND: Laparoscopic distal gastrectomy has become an established minimally invasive treatment for gastric cancer since it was first reported in 1994. MATERIALS AND METHODS: We retrospectively assessed the clinical outcomes of 248 patients who had undergone open distal gastrectomy (ODG), laparoscopic-assisted distal gastrectomy (LADG), and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. RESULTS AND CONCLUSIONS: TLDG showed superiority in terms of blood loss, reconstruction options, and postoperative recovery compared with ODG and LADG. Especially, the mean operating time in the TLDG group was significantly shorter than that of the LADG group (P=0.003). Book-binding technique used in TLDG was one of the reasons of this result. The only inferior aspect of TLDG was the longer operating time compared with ODG; TLDG had no disadvantages compared with LADG. Although the operating time and long-term outcome remain problems, we suggest that TLDG has the potential to serve as an optimal operative method. PMID- 27552378 TI - Clinical outcomes and economic impact of transcatheter mitral leaflet repair in heart failure patients. AB - BACKGROUND: Mitral regurgitation (MR) is a common valvular heart disorder requiring intervention once it becomes severe. Transcatheter mitral repair with the MitraClip device is a safe and effective therapy for selected patients denied surgery. The authors sought to evaluate the clinical outcomes and economic impact of this therapy compared to medical management in heart-failure patients with symptomatic mitral regurgitation. METHODS AND RESULTS: The study was comprised of two phases; an observational study of patients with heart failure and mitral regurgitation treated with either medical therapy or the MitraClip, and an economic model. Results of the observational study were used to estimate parameters for the decision model, which estimated costs, and benefits in a hypothetical cohort of patients with heart failure and moderate-to-severe mitral regurgitation treated with either standard medical therapy or MitraClip. The cohort of patients treated with the MitraClip was propensity matched to a population of heart failure patients, and their outcomes compared. At a mean follow-up of 22 months, all-cause mortality was 21% in the MitraClip cohort and 42% in the medical management cohort (p = .007). The decision model demonstrated that MitraClip increased life expectancy from 1.87-3.60 years and quality adjusted life years (QALY) from 1.13-2.76 years. The incremental cost was $52,500 Canadian dollars, corresponding to an incremental cost-effectiveness ratio (ICER) of $32,300.00 per QALY gained. Results were sensitive to the survival benefit. CONCLUSION: In heart failure patients with symptomatic moderate-severe mitral regurgitation, therapy with the MitraClip is associated with superior survival and is cost-effective compared to medical therapy. PMID- 27552379 TI - Toward Spatiotemporally Controlled Synthesis of Photoresponsive Polymers: Computational Design of Azobenzene-Containing Monomers for Light-Mediated ROMP. AB - Density functional theory calculations have been used to identify the optimum design for a novel, light-responsive ring monomer expected to allow spatial and temporal control of ring-opening metathesis polymerization (ROMP) via light mediated changes in ring strain energy. The monomer design leverages ring-shaped molecules composed of 4,4'-diaminoazobenzene (ABn) closed by alkene-alpha,omega dioic acid linkers. The atomic geometries, formation enthalpies and ring strain energies of azobenzene (AB)-containing rings with various length linkers have been calculated. The AB(2,2) monomer is identified as having optimal properties for light-mediated ROMP, including high thermodynamic stability, low ring strain energy (RSE) with cis-AB, and high RSE with trans-AB. Time-dependent DFT calculations have been used to explore the photoisomerization mechanism of isolated AB and AB-containing rings, and calculations show that trans-to-cis and cis-to-trans photoisomerization of the optimal AB(2,2) ring molecule can be achieved with monochromatic green and blue light, respectively. The AB(2,2) monomer identified here is expected to allow precise, reversible, spatial and temporal light-mediated control of ROMP through AB photoisomerization, and to have promising potential applications in the fabrication of patterned and/or responsive AB-containing polymer materials. PMID- 27552380 TI - The predictive value of FDG-PET with 3D-SSP for surgical outcomes in patients with temporal lobe epilepsy. AB - PURPOSE: We retrospectively evaluated the diagnostic value of (18)F-2-fluorodeoxy d-glucose positron emission tomography (FDG-PET) with statistical analysis for the foci detection and predictive utility for postsurgical seizure outcome of patients with mesial temporal lobe epilepsy (mTLE). METHOD: We evaluated 40 patients who were diagnosed mTLE and underwent selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) in our institute. Preoperative interictal FDG-PET with statistical analysis using three-dimensional stereotactic surface projection (3D-SSP) was detected with several clinical data including seizure semiology, MRI, scalp electroencephalography, surgical procedure with SAH or ATL and postsurgical outcome. The region of interest (ROI) was defined on 'Hippocampus & Amygdala', 'Parahippocampal gyrus & Uncus', 'T1 & T2', and 'T3 & Fusiform gyrus'. We obtained the ratio of hypometabolism difference (RHD) by 3D SSP, and evaluated the relation among hypometabolic extent, surgical outcome and surgical procedure. RESULT: The RHD in each ROIs ipsilateral to operative side was significantly higher than that of contralateral side in good outcome group. Hypometabolism of 'Hippocampus & Amygdala' was most reliable prognostic factor. Patients of discordant with presurgical examinations hardly showed obvious lateralized hypometabolism. Nevertheless, when they have significantly high RHD in mesial temporal lobe, good surgical outcome was expected. There was not significant difference of RHD distribution between SAH and ATL in good outcome group. CONCLUSION: Significant hypometabolism in mesial temporal lobe on FDG-PET with 3D-SSP is useful to predict good surgical outcome for patients with mTLE, particularly in discordant patients with hypometabolism in mesial temporal structure. However, FDG-PET is not indicative of surgical procedure. PMID- 27552381 TI - Overview of accessibility and quality of antiepileptic drugs in Madagascar. AB - PURPOSE: To determine the accessibility of treatment and the quality of antiepileptic drugs (AEDs) in the Haute Matsiatra district of Madagascar. METHODS: Cross-sectional descriptive study and interviews. Samples of 10 units of each available AED were collected, and the active ingredient was quantified by reversed-phase high-performance liquid chromatography (RP-HPLC) with photodiode array UV detection. The quality of an AED was considered satisfactory if the quantity of active ingredient in each tablet was in the range +/-15% of the average value according to the European Pharmacopeia (6th edition, 2008). RESULTS: The area was well served with health infrastructure but rescue facilities were poorly distributed. Available AEDs were all first-generation, and 73% were generic formulations. People with epilepsy (PWE) surveyed consulted traditional healers and most were treated with plants. PWE did not consider themselves sick but believed they were "possessed"; they consulted a doctor only immediately after a seizure, following the advice of traditional healers. The most prescribed AED was phenobarbital, costing between 0.03 and 0.12 US Dollar (US$) per 100mg. The purchase of full treatment was difficult for 77% of PWE and as a result, 39% took nothing. The quality of AEDs were considered unsatisfactory in 2.8% of cases. CONCLUSION: The AEDs collected in Haute Matsiatra were globally of good quality. The main limiting elements were a lack of knowledge among PWE that epilepsy is a disease, and the cost of traditional treatments. PMID- 27552382 TI - Local endemism and within-island diversification of shrews illustrate the importance of speciation in building Sundaland mammal diversity. AB - Island systems are important models for evolutionary biology because they provide convenient, discrete biogeographic units of study. Continental islands with a history of intermittent dry land connections confound the discrete definitions of islands and have led zoologists to predict (1) little differentiation of terrestrial organisms among continental shelf islands and (2) extinction, rather than speciation, to be the main cause of differences in community composition among islands. However, few continental island systems have been subjected to well-sampled phylogeographic studies, leaving these biogeographic assumptions of connectivity largely untested. We analyzed nine unlinked loci from shrews of the genus Crocidura from seven mountains and two lowland localities on the Sundaic continental shelf islands of Sumatra and Java. Coalescent species delimitation strongly supported all currently recognized Crocidura species from Sumatra (six species) and Java (five species), as well as one undescribed species endemic to each island. We find that nearly all species of Crocidura in the region are endemic to a single island and several of these have their closest relative(s) on the same island. Intra-island genetic divergence among allopatric, conspecific populations is often substantial, perhaps indicating species-level diversity remains underestimated. One recent (Pleistocene) speciation event generated two morphologically distinct, syntopic species on Java, further highlighting the prevalence of within-island diversification. Our results suggest that both between- and within-island speciation processes generated local endemism in Sundaland, supplementing the traditional view that the region's fauna is relictual and primarily governed by extinction. This article is protected by copyright. All rights reserved. PMID- 27552383 TI - Human Immunoglobulin Versus Plasmapheresis in Guillain-Barre Syndrome and Myasthenia Gravis: A Meta-Analysis. AB - OBJECTIVES: To evaluate the efficacy and safety over a short time period of human intravenous immunoglobulin versus plasma exchange (PE) in the management of some autoimmune neurologic diseases. In addition, length of hospital stay and duration of ventilator support were compared. METHODS: Randomized controlled trials and analytical observational studies of more than 10 cases were reviewed. Cochrane Neuromuscular Disease Group trials, MEDLINE, EMBASE, HINARI, and Ovid, were searched as data source. Reference lists were examined for further relevant articles. A random-effect model was used to derive a pooled risk ratio. RESULTS: A total of 552 articles were found and 24 met the criteria for a studied population of 4657 cases: 14 articles were about Guillain-Barre syndrome and 10 of myasthenia gravis. No evidence was found to suggest that PE or intravenous immunoglobulin differed in terms of efficacy or safety to treat any of the 2 diseases. Hospital stay length and ventilatory support time are different in each illness; however, we found no statistical difference in either of the 2 treatments. CONCLUSIONS: There is no evidence for superiority in the efficacy or safety of immunoglobulin or plasmapheresis in the management of Guillain-Barre syndrome and myasthenia gravis. However, caution should be exercised in the interpretation of these results given the limitations in the quality of the evidence and the heterogeneity of the studies. PMID- 27552384 TI - A Review of Azathioprine-Associated Hepatotoxicity and Myelosuppression in Myasthenia Gravis. AB - OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disorder in which antibodies interfere with neuromuscular transmission. Azathioprine (AZA) is an immunosuppressant frequently used for treatment of various autoimmune conditions, including MG. The literature suggests that the rates of AZA-associated hepatotoxicity and myelosuppression in MG are highly variable. Published studies have not formally analyzed their pattern, severity, timing, and/or recovery. We assessed the prevalence, pattern and timing of AZA associated toxicity in a large group of MG patients. METHODS: We identified 113 patients with MG with AZA associated toxicity among 571 managed with this immunosuppressant. The timing of when toxicities occurred as well as pattern of laboratory abnormalities was assessed. RESULTS: The overall prevalence of hepatotoxicity and myelosuppression was 15.2% and 9.1%, respectively. The most common pattern of hepatotoxicity seen was gamma-glutamyl transpeptidase (GGT) enzyme elevation in 67.8% of patients. Of note, 21.2% of patients with myelosuppression had normocytic anemia, 17.3% had pancytopenia, and another 17.3% developed macrocytic anemia. CONCLUSIONS: AZA associated hepatotoxicity and myelosuppression in MG are not uncommon and may be underrecognized depending on the timing, frequency, and specific tests ordered for blood work monitoring. PMID- 27552385 TI - Comparative Long-Term Evaluation of Patients With Juvenile Inflammatory Myopathies. AB - OBJECTIVES: We conducted a retrospective study analyzing the clinical features, laboratory findings, demographics, and long-term prognoses of patients with juvenile inflammatory myopathies to determine possible predictors indicating the use of aggressive immunotherapy and the response to and complications of treatment. METHODS: The medical records of 41 patients with juvenile inflammatory myopathies seen at University of Tennessee-affiliated hospitals in Memphis from 1969 to 2008 were evaluated. Patients' clinical characteristics, laboratory studies, muscle biopsies, and electromyography were reviewed. All patients were treated with prednisone initially; additionally, 14 patients received varying combinations of other immunosuppressant therapies. RESULTS: Seventy-three percent of the patients experienced remission. Patients in the group that did not go into remission had specific characteristics at onset: they were comparatively older and had more severe rashes, contractures, arthritis, and systemic involvement. Also, patients with positive autoantibodies (antinuclear antibody, rheumatoid arthritis factor) had better outcomes. CONCLUSIONS: Juvenile inflammatory myopathies have relatively good prognoses. Initial presentation at advanced age or with severe rash, systemic vasculopathies, anemia, or arthritis portends refractory disease; in these patients, second- and third-line therapies improve outcome. PMID- 27552386 TI - Ulnar Neuropathy at the Elbow in Chronic Alcohol-Dependent Subjects. AB - OBJECTIVES: To evaluate the occurrence of Ulnar neuropathy at the elbow (UNE) among alcohol dependent subjects. METHOD: The study sample comprised 99 consecutive alcohol dependent subjects treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic in an inpatient basis. RESULTS: UNE was found in 51 subjects (51.5%): in 40.4% on the right side, in 44.6% on the left and in 20.1% on both. Polyneuropathy was diagnosed in 41.4% of the total sample. Statistical analysis showed UNE significantly associated with age of the subjects, age at alcohol dependence onset and duration of alcohol dependence. Was more frequent in men and the probability of UNE was lower in obese subjects. CONCLUSIONS: UNE is frequent among alcohol dependent subjects and they must be instructed to avoid abnormal postures and to protect their elbow while working with the elbows flexed and resting on a hard object. PMID- 27552387 TI - Bilateral Vestibulopathy Aggravates Balance and Gait Disturbances in Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis: A Case Report. AB - In patients with a triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), the presenting features are mainly ataxia or ptosis. SANDO patients often have impaired balance and gait, which is not surprising considering the combination of sensory ataxic neuropathy, and additional symptoms like cerebellar ataxia and limb girdle weakness. We describe a SANDO patient who noticed an increasingly impaired balance and gait, without any dizziness. Neurological investigation revealed an external ophthalmeplegia and a cerebellar ataxia; the head impulse test was not reliable because of eye movement disorders. The caloric reflex tests showed lack of responses on both sides, compatible with severe bilateral vestibulopathy. Making the diagnosis of bilateral vestibulopathy in SANDO patients may have implications for the management of the patient, because specific vestibular rehabilitation can improve gaze and postural stability. PMID- 27552388 TI - Small Fiber Neuropathy Following Vaccination. AB - OBJECTIVE: To identify clinical and quantitative relationship between vaccinations and small fiber neuropathy (SFN). SFN refers to damaged unmyelinated or thinly myelinated sensory and/or autonomic fibers. Diagnosis is primarily based on clinical presentation. Intraepidermal nerve fiber density can provide diagnostic confirmation with a sensitivity of 88% and a specificity of 91%. However, the possible association between vaccination and small fiber polyneuropathy is not well defined. METHODS: Case study. RESULTS: Fourteen-year old white adolescent girl presented with intractable generalized pain for 1.5 years. Burning dysesthetic pain began in the lower back and progressed to all extremities 9 days following human papillomavirus vaccination. The pain persisted despite various pain medications. Examination was significant for allodynia of right scapula (T4-T6) and decreased pinprick sensation in feet. MRI Brain with and without contrast, MR Face, Orbit with and without contrast, and MR Cervical, Lumbar spines with and without contrast were all normal. Nerve Conduction Studies/Electromyogram studies were unremarkable, and skin biopsy of the right thigh and foot showed low intraepidermal nerve fiber density with normal sweat gland nerve fiber density. CONCLUSIONS: This case report describes an acute onset of non-length-dependent SFN potentially related to human papillomavirus vaccine administration. Literature review includes several similar case studies, and various pathological processes have been proposed for vaccine-associated polyneuropathies. Some theories describe immune-mediated hypersensitivity to the solvents/adjuvants and/or invasion of nervous system through a prolonged, less virulent infection. However, the lack requires that evidence must be carefully reviewed. PMID- 27552389 TI - MRI Ventral Nerve Root Enhancement in Five Patients Presenting With Extremity Weakness Secondary to Neuroinvasive West Nile Virus. PMID- 27552390 TI - Meralgia Paresthetica in Subcutaneous Interferon Alpha Treatment. PMID- 27552391 TI - Sensory Neuronopathy in Spinal Muscular Atrophy: A Case Presentation. PMID- 27552392 TI - What's in the Literature? AB - The Guillain-Barre syndrome (GBS) is one of the few neuropathies well known to the general public, in part because of its association with swine flu vaccinations in 1976. GBS has again reached the general public with its possible association with Zika virus. The virus, borne by infected Aedes aegypti mosquitos, is being linked to birth defects when pregnant women are bitten and infected. There are early reports also linking GBS to Zika infection, which could expose a wider range of infected people to the neuropathy. This summer infected Aedes mosquitos will likely reach southern portions of the United States, and travelers to countries where Aedes is endemic will increase. It is important to appreciate that the neurologic consequences of Zika virus are being actively investigated, and firm associations and consequences are yet to be established. Small fiber neuropathies are common and can be due to a number of underlying diseases, and a recent review also indicates that many are idiopathic. One cause is Sjogren syndrome, and a case series reviews clinical features. The diagnosis and underlying features of primary lateral sclerosis are a clinical challenge. Similarities between primary lateral sclerosis and hereditary spastic paraparesis (HSP) have long been noted. With a wide spectrum of gene mutations associated with HSP, clinical distinction between the 2 disorders is problematic. A review covers the wide spectrum of HSP. With no cure, the progression of amyotrophic lateral sclerosis (ALS) to respiratory failure is predictable. This could easily result in marked depression among patients, and 2 studies have explored the frequency and severity of depression. The cause of ALS remains unknown, and when no hereditary factor is apparent, environmental questions arise as possible contributing factor(s). The most notable association is with military service, although specific occupational or environmental linkages are not well sorted out. Two recent reports address these issues. There is good news for ALS patients with muscle cramps with the results of a multicenter randomized and placebo-controlled trial showing that mexiletine is effective in reducing this common symptom. The treatment of myasthenia gravis with various agents, the use of patient-reported outcome measures in myasthenia gravis, and the occurrence of myocarditis in this disease are reviewed. Necrotizing autoimmune neuropathies, the co-occurrence of inclusion body myositis and a form of T-cell leukemia are discussed as are valosin-containing protein (VCP)-opathy and bone health in patients with dystrophinopathy. PMID- 27552393 TI - Immunoglobulin replacement therapy reduces chronic rhinosinusitis in patients with antibody deficiency. AB - BACKGROUND: Patients with primary antibody deficiencies have an increased frequency of sinonasal and pulmonary infections. Immunoglobulin (Ig) replacement is a standard therapy for common variable immunodeficiency (CVID) and other antibody deficiency diseases. Although there is convincing evidence that Ig replacement reduces pulmonary infections, there is little evidence that it reduces sinus infections or abates chronic rhinosinusitis (CRS). This study aims to identify the impact of Ig replacement on CRS in antibody deficiencies. METHODS: A single-center, retrospective chart review of adult patients from 1995 to 2015 was performed. Inclusion criteria were diagnosis of CVID or specific antibody deficiency (SAD), history of CRS requiring medical and/or surgical management within the year prior to presentation, treatment with Ig replacement therapy, and follow-up interval of at least 1 year after initiating Ig replacement. Patients with secondary immune deficiencies were excluded. Thirty one patients met criteria. Data collected included pretreatment and posttreatment Lund-Mackay scores, and frequency of sinusitis and pulmonary infections requiring rescue antibiotics. Statistical analysis was performed using Wilcoxon signed-rank tests. RESULTS: A significant decline in the Lund-Mackay score was evidenced from pretreatment to posttreatment (p < 0.01). Treatment also resulted in significantly lower rates of sinusitis (p < 0.01) and pulmonary infections (p < 0.01). Additionally, 56% of patients who were on prophylactic antibiotics prior to Ig replacement were able to discontinue their use. CONCLUSION: We present objective evidence showing that Ig replacement therapy has a positive impact on the frequency of sinusitis and confirm its positive impact on pulmonary infections in adult patients with CVID and SAD. PMID- 27552394 TI - Living in the Shadows: Plight of the Undocumented. AB - The word "immigration" has become a household buzzword. The welcome sign on the Statue of Liberty that reads, "Give me your tired, your poor, your huddled masses yearning to breathe free," however, is fading and has been replaced by many complicated conditions. What to do with the very large number of undocumented immigrants living in the United States and arriving at the United States every day commands considerable attention and has been the subject of breaking stories in the news. Working in the field of immigration demands an awareness of and sensitivity to diversity and cultural competence. Despite a "hot" sociopolitical climate when it comes to undocumented aliens and what to do with them, there are many ethical tenets that psychologists must be familiar with, among them rendering competent multicultural services. This article offers an overview of immigration law, the challenges of performing culturally competent assessments and consequences of failing to do so, and the plight of a particularly vulnerable group: unaccompanied children. Vignettes offer a personal look into the proceedings of 7 undocumented individuals in 4 major areas: asylum, hardship, U Visa, and VAWA. PMID- 27552395 TI - Environmental impacts of engineered nanomaterials-Our current understanding. PMID- 27552396 TI - Smell no evil: Copper disrupts the alarm chemical response in a diadromous fish, Galaxias maculatus. AB - Fish, at all life stages, utilize olfactory information in the decision-making processes essential to survival. Olfaction is a sensitive sensory process, and toxicants within urban aquatic environments can have destructive or depreciating effects. In the present study, the authors exposed Galaxias maculatus, a native fish commonly found in urban waterways throughout southeastern Australia, to 1 of 5 ecologically relevant copper (II) chloride concentrations (<1 MUg/L, 1 MUg/L, 6 MUg/L, 8 MUg/L, 18 MUg/L) for 16 h. After exposure, the authors tested the response of individual fish to 1 of 3 stimuli: a conspecific skin extract containing a stress-inducing alarm chemical odor, a conspecific odor, and distilled water as a control. Stress responses were quantified through behavioral assays. The authors found evidence for distinct changes in behavioral response with increasing copper concentration and a marked difference in response between control fish and fish exposed to the alarm chemical odor. Copper, even at relatively low concentrations, can have a significant effect on the stress response behavior shown by G. maculatus. Environ Toxicol Chem 2016;35:2209-2214. (c) 2016 SETAC. PMID- 27552397 TI - Human health risk assessment of triclosan in land-applied biosolids. AB - Triclosan (5-chloro-2-[2,4-dichlorophenoxy]-phenol) is an antimicrobial agent found in a variety of pharmaceutical and personal care products. Numerous studies have examined the occurrence and environmental fate of triclosan in wastewater, biosolids, biosolids-amended soils, and plants and organisms exposed to biosolid amended soils. Triclosan has a propensity to adhere to organic carbon in biosolids and biosolid-amended soils. Land application of biosolids containing triclosan has the potential to contribute to multiple direct and indirect human health exposure pathways. To estimate exposures and human health risks from biosolid-borne triclosan, a risk assessment was conducted in general accordance with the methodology incorporated into the US Environmental Protection Agency's Part 503 biosolids rule. Human health exposures to biosolid-borne triclosan were estimated on the basis of published empirical data or modeled using upper-end environmental partitioning estimates. Similarly, a range of published triclosan human health toxicity values was evaluated. Margins of safety were estimated for 10 direct and indirect exposure pathways, both individually and combined. The present risk assessment found large margins of safety (>1000 to >100 000) for potential exposures to all pathways, even under the most conservative exposure and toxicity assumptions considered. The human health exposures and risks from biosolid-borne triclosan are concluded to be de minimis. Environ Toxicol Chem 2016;35:2358-2367. (c) 2016 SETAC. PMID- 27552398 TI - FIRST-GENERATION LATINA MOTHERS' EXPERIENCES OF SUPPLEMENTING HOME-BASED EARLY HEAD START WITH THE ATTACHMENT AND BIOBEHAVIORAL CATCH-UP PROGRAM. AB - This qualitative pilot study examined first-generation Latina mothers' experiences of supplementing home-based Early Head Start (EHS) services with the evidence-based Attachment and Biobehavioral Catch-up (ABC; M. Dozier, O. Lindheim, & J. Ackerman, 2005) program. Ten low-income, first-generation Latina mothers with infants and toddlers enrolled in home-based EHS were provided 10 ABC home visits by a supplemental parent coach. Following delivery of ABC, mothers participated in in-depth, semistructured, qualitative interviews about their experiences. Interview themes included positive experiences of both EHS and the ABC, a high value placed on receiving both programs, and cultural relevance of the ABC program for Latino families. Participants offered several suggestions for improved program delivery. Study findings suggest that a model of EHS supplemented by ABC delivered to the Latino community is feasible, valuable to participants, and culturally relevant. Considerations for sustainability of this supplemental model are discussed. PMID- 27552399 TI - Scalable Synthesis of Anomerically Pure Orthogonal-Protected GlcN3 and GalN3 from d-Glucosamine. AB - An improved and scalable synthesis of orthogonally protected d-glucosamine and d galactosamine building blocks from inexpensive d-glucosamine has been developed. The key reaction is an inversion/migration step providing access to a fully orthogonal protecting group pattern, which is required for microbial oligosaccharide synthesis. The method can be carried out on a multigram scale as several of the reactions can be purified by crystallization to give anomerically pure products. PMID- 27552400 TI - GC-MS metabolomics analysis of mesenchymal stem cells treated with copper oxide nanoparticles. AB - Human exposure to copper oxide (CuO) nanoparticles (NPs) is rapidly increasing and for this reason reliable toxicity test systems are urgently needed. Recently, the acute cytotoxicity of CuO NPs using the new toxicity test based on human bone marrow mesenchymal stem cells (hBMMSCs) has been evaluated. It was shown that CuO NPs are much more toxic when compared to CuO microparticles (MPs). Several studies associate CuO toxicity to a possible alteration of reactive oxygen species (ROS) system. Unluckily, the mechanism that causes the toxicity is still not clear. In this work, the polar metabolite pool of treated cells, at the corresponding IC50 value, for CuO micro and NPs has been studied by gas chromatography coupled to mass spectrometry (GC-MS) and multivariate statistical data analysis. By the same means, differences due to different treatments, on samples, were investigated. Results of discriminant analysis were considered with the aim of finding the relevant metabolites unique for each class. Serine, glyceric acid, and succinic acid were upregulated on samples treated with CuO microparticles, while glutamine was the only discriminant metabolite for the class of samples treated with nanoparticles. PMID- 27552401 TI - Therapeutic touch for healing acute wounds. AB - BACKGROUND: Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. OBJECTIVES: To identify and review all relevant data to determine the effects of TT on healing acute wounds. SEARCH METHODS: In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. DATA COLLECTION AND ANALYSIS: One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. MAIN RESULTS: No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. AUTHORS' CONCLUSIONS: There is no robust evidence that TT promotes healing of acute wounds. PMID- 27552402 TI - Decomposing the First Absorption Band of OCS Using Photofragment Excitation Spectroscopy. AB - Photofragment excitation spectra of carbonyl sulfide (OCS) have been recorded from 212-260 nm by state-selectively probing either electronically excited S((1)D) or ground state S((3)P) photolysis products via 2 + 1 resonance-enhanced multiphoton ionization. Probing the major S((1)D) product results in a broad, unstructured action spectrum that reproduces the overall shape of the first absorption band. In contrast, spectra obtained probing S((3)P) products display prominent resonances superimposed on a broad continuum; the resonances correspond to the diffuse vibrational structure observed in the conventional absorption spectrum. The vibrational structure is assigned to four progressions, each dominated by the C-S stretch, nu1, following direct excitation to quasi-bound singlet and triplet states. The S((3)PJ) products are formed with a near statistical population distribution over the J = 2, 1, and 0 spin-orbit levels across the wavelength range investigated. Although a minor contributor to the S atom yield near the peak of the absorption cross section, the relative yield of S((3)P) increases significantly at longer wavelengths. The experimental measurements validate recent theoretical work characterizing the electronic states responsible for the first absorption band by Schmidt and co-workers. PMID- 27552403 TI - Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors: A Retrospective Study. AB - OBJECTIVES: The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary. METHODS: This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed. RESULTS: One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%. CONCLUSIONS: Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms. PMID- 27552404 TI - Oncologic Safety of Laparoscopy in the Surgical Treatment of Type II Endometrial Cancer. AB - BACKGROUND: Laparoscopy is considered the method of choice in the operative treatment of type I endometrial carcinoma (EC). However, there is a paucity of data regarding the safety of endoscopy for type II EC because these malignancies have several biological similarities with ovarian cancer. OBJECTIVES: This study aimed to evaluate the feasibility, operative outcomes, and oncologic safety of laparoscopic surgery in patients with type II EC. METHODS: A retrospective study with histologically confirmed serous or clear-cell EC without peritoneal carcinomatosis treated by laparoscopy (G1) or laparotomy (G2) was conducted. Procedures included hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. RESULTS: From 2009 to 2015, 89 patients were included; 53 women underwent laparoscopy and 36 underwent laparotomy. No relevant epidemiological or oncologic difference between groups was observed. The mean number of removed pelvic nodes was 16 [+/-10] and 12 [+/ 13] in group 1 (G1) and group 2 (G2), respectively (P = 0.127). The mean number of dissected para-aortic nodes was significantly greater in the laparoscopic group (11 [+/-9] vs 6 [+/-9], P = 0.006). Para-aortic metastasis was significantly more often observed in the endoscopy group (26% vs 13%, P = 0.04). Adjuvant therapies were given to 86% of the patients in the study and 75% in the control group (P = 0.157). No excessive blood loss, casualty related to surgery, intraoperative complication, or conversion to laparotomy occurred in G1. Ten (18%) women from G1 and 36% (13/36) in G2 developed relevant postoperative complications (P = 0.03). The median duration of follow-up was 38 months for the laparoscopy and 47 months for the open surgery (P = 0.12). The 5-year overall and disease-free survival were similar, 86% versus 78% and 58% versus 51% for G1 and G2, respectively (P = 0.312). CONCLUSIONS: Laparoscopy is oncologically at least not inferior to laparotomy for the surgical treatment of type II EC. Endoscopic techniques are feasible, effective, result in significantly less morbidity, and improved quality staging. Although statistical significance was not reached, laparoscopy was associated with superior oncologic results. PMID- 27552405 TI - Distinct evolutionary paths to TKI resistance in NSCLC. PMID- 27552407 TI - Gene Signature-Based Development of ELISA Assays for Reproducible Qualification of Cultured Human Corneal Endothelial Cells. AB - PURPOSE: To develop a method to qualify the function of cultured human corneal endothelial cells (cHCECs) applicable for clinical settings. METHODS: The diversified gene and microRNA (miRNA) signatures in HCECs from a variety of tissue donors were confirmed by three-dimensional (3D) gene human miRNA profiling. These were compared with those of more than 20 cHCECs distinct in their cell morphology or culture lots. Candidate genes were selected after quantitative (q)RT-PCR validation, and gene products were assayed by ELISA. After three additional screening steps, final candidate cytokines for qualification were selected. RESULTS: Gene and miRNA signatures among distinct cHCEC lots were greatly diversified compared with those among fresh tissues from different age donors. By comparing more than 20 lots of cultures, 32 candidate genes were assigned to be seemingly linked to distinct cHCEC morphologic features. The validation of candidate genes by qRT-PCR revealed the genes, either upregulated or downregulated, corresponding to morphologic variances in cHCECs (e.g., epithelial-mesenchymal transition or cell senescence). Further adding the ELISA results by Bio-Plex Human Cytokine 27-Plex Panel, 11 candidate cytokines suitable to qualify cHCEC function were selected. In consideration of the presence of these cytokines in the anterior chamber, IL-8, tissue inhibitors of metalloproteinases 1 (TIMP-1), monocyte chemotactic protein-1 (MCP-1), and platelet-derived growth factor-BB (PDGF-BB) were ultimately selected and applied in practice for the qualification of cHCECs actually used in our clinical cell injection studies. CONCLUSIONS: The specified cytokines properly discriminating the functional features of cHCECs indicates a correlation between profiling signatures and cell morphology. PMID- 27552406 TI - Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells? AB - PURPOSE: Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. METHODS: Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. RESULTS: Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. CONCLUSIONS: Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival. PMID- 27552408 TI - Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia. AB - PURPOSE: The purpose of this study was to investigate the effects of sildenafil on retinal injury following neonatal hypoxia-ischemia (HI) at term-equivalent age in rat pups. METHODS: Hypoxia-ischemia was induced in male Long-Evans rat pups at postnatal day 10 (P10) by a left common carotid ligation followed by a 2-hour exposure to 8% oxygen. Sham-operated rats served as the control group. Both groups were administered vehicle or 2, 10, or 50 mg/kg sildenafil, twice daily for 7 consecutive days. Retinal function was assessed by flash electroretinograms (ERGs) at P29, and retinal structure was assessed by retinal histology at P30. RESULTS: Hypoxia-ischemia caused significant functional (i.e., attenuation of the ERG a-wave and b-wave amplitudes and photopic negative response) and structural (i.e., thinning of the total retina, especially the inner retinal layers) retinal damage in the left eyes (i.e., ipsilateral to the carotid ligation). Treatment with the different doses of sildenafil led to a dose-dependent increase in the amplitudes of the ERG a- and b-waves and of the photopic negative response in HI animals, with higher doses associated with greater effect sizes. Similarly, a dose response was observed in terms of improvements in the retinal layer thicknesses. CONCLUSIONS: Hypoxia-ischemia at term-equivalent age induced functional and structural damage mainly to the inner retina. Treatment with sildenafil provided a dose-dependent recovery of retinal function and structure. PMID- 27552409 TI - Association of Hyperreflective Foci Present in Early Forms of Age-Related Macular Degeneration With Known Age-Related Macular Degeneration Risk Polymorphisms. AB - PURPOSE: We evaluated the association of hyperreflective foci (HF) observed in early and intermediate age-related macular degeneration (AMD) with known AMD risk alleles. METHODS: In this pilot case-control study, HF were defined as lesions with reflectivity equal or higher than the retinal pigment epithelium band in spectral domain optical coherence tomography (SDOCT). Hyperreflective foci in the outer nuclear layer and photoreceptor complex were evaluated in 518 individuals with early and intermediate AMD. Definite presence of HF was defined as at least 10 HF in all SDOCT scans. Genotyping was performed for 22 single nucleotide polymorphisms (SNPs). Associations between AMD severity stages, HF, and SNPs were determined by logistic regression analyses. RESULTS: Hyperreflective foci (n >= 10) were significantly associated with AMD severity and the association was strongest with intermediate AMD (odds ratio [OR], 8.45; P = 1.092*10-8). Independently, HF showed associations with ARMS2 rs104909/HtRA1 rs11200638 (OR, 1.64; P = 0.017), CFH rs1061170 (OR, 1.70; P = 0.011), and APOE4/TOMM40 rs2075650 (OR, 2.26; P = 0.005) variants. Within the group of intermediate AMD, associations were similar (ARMS2 rs104909/HtRA1 rs11200638 OR, 1.79, P = 0.010; CFH rs1061170 OR, 1.77, P = 0.013; APOE4/TOMM40 rs2075650 OR, 1.98; P = 0.034) and showed additional trending associations with VEGFA rs943080 variant (OR, 0.59; P = 0.024). After Bonferroni-correction for 22 SNPs, none of the associations was statistically significant (P <= 0.0023). CONCLUSIONS: The presence of HF is related to AMD severity. Despite limited power of this pilot study, our results suggest an association of HF with polymorphisms in ARMS2/HTRA1, CFH, APOE4/TOMM40, and VEGFA genes which could be triggered by modification of the extracellular matrix, altered complement system or lipid metabolism. PMID- 27552410 TI - Stereoscopic Viewing Can Induce Changes in the CA/C Ratio. AB - PURPOSE: Stereoscopic displays challenge the neural cross-coupling between accommodation and vergence by inducing a constant accommodative demand and a varying vergence demand. Stereoscopic viewing calls for a decrease in the gain of vergence accommodation, which is the accommodation caused by vergence, quantified by using the convergence-accommodation to convergence (CA/C) ratio. However, its adaptability is still a subject of debate. METHODS: Cross-coupling (CA/C and AC/A ratios) and tonic components of vergence and accommodation were assessed in 12 participants (27.5 +/- 5 years, stereoacuity better than 60 arc seconds, 6/6 acuity with corrected refractive error) before and after a 20-minute exposure to stereoscopic viewing. During stimulation, vergence demand oscillated from 1 to 3 meter angles along a virtual sagittal line in sinusoidal movements, while accommodative demand was fixed at 1.5 diopters. RESULTS: Results showed a decreased CA/C ratio (-10.36%, df = 10, t = 2.835, P = 0.018), with no change in the AC/A ratio (P = 0.090), tonic vergence (P = 0.708), and tonic accommodation (P = 0.493). CONCLUSIONS: These findings demonstrated that the CA/C ratio can exhibit adaptive adjustments. The observed nature and amount of the oculomotor modification failed to compensate for the stereoscopic constraint. PMID- 27552411 TI - A meta-ethnography of interview-based qualitative research studies on medical students' views and experiences of empathy. AB - BACKGROUND: Quantitative research suggests that medical students' empathy declines during their training. This meta-ethnography asks: What new understanding may be gained by a synthesis of interview-based qualitative research on medical students' views and experiences of empathy? How can such a synthesis be undertaken? METHODOLOGY: A meta-ethnography synthesizes individual qualitative studies to generate knowledge increasing understanding and informing debate. A literature search yielded eight qualitative studies which met the inclusion criteria. These were analyzed from a phenomenological and interpretative perspective. RESULTS: The meta-ethnography revealed a conceptual confusion around empathy and a tension in medical education between distancing and connecting with patients. Barriers to empathy included a lack of patient contact and a strong emphasis on the biomedical over the psycho-social aspects of the curriculum. A number of influences discussed in the paper lead students to adopt less overt ways of showing their empathy. CONCLUSION: These insights deepen our understanding of the apparent decline in empathy in medical students. The lessons from these studies suggest that future curriculum development should include earlier patient contact, more emphasis on psycho-social aspects of care and address the barriers to empathy to ensure that tomorrow's doctors are empathetic as well as competent. PMID- 27552412 TI - Liquid crystal physical gel formed by cholesteryl stearate for light scattering display material. AB - A liquid crystal physical gel was prepared by the self-assembly of cholesteryl stearate in a nematic liquid crystal, 4-cyano-4'-pentylbiphenyl. The electro optical properties were tuned by varying the gelator concentration and the gelation conditions. Polarized optical microscopy revealed that cholesteric cholesteryl stearate induced chiral nematic phase in 4-cyano-4'-pentylbiphenyl during the gelation process. As a result, a plate-like gel structure consisting of spherical micropores was formed, as observed by scanning electron microscopy. Electron spin resonance spectroscopy showed that the liquid crystal director orientations in these macrophase-separated structures were massively randomised. For these reasons, the liquid crystal physical gel generated a strong light scattering effect. For 48.0wt% cholesteryl stearate gelled 4-cyano-4' pentylbiphenyl, the turbid appearance could be switched to a transparent state using a 5.0V alternating current. The response time was about 3.7MUs. This liquid crystal physical gel has potential for use in light scattering electro-optical displays. PMID- 27552413 TI - Enhanced photocatalytic performance of morphologically tuned Bi2S3 NPs in the degradation of organic pollutants under visible light irradiation. AB - Here in, morphologically tuned Bi2S3 NPs were successfully synthesized from a single-source precursor complex [Bi(ACDA)3] [HACDA=2-aminocyclopentene-1 dithiocarboxylic acid] by decomposing in various solvents using a simple solvothermal method. The as-obtained products were characterized by XRD, TEM, UV vis spectroscopy and BET surface area measurements. Structural analyses revealed that the as-prepared Bi2S3 NPs can be tuned to different morphologies by varying various solvents and surfactants. The interplay of factors that influenced the size and morphology of the nanomaterials has been studied. Moreover, mastery over the morphology of nanoparticles enables control of their properties and enhancement of their usefulness for a given application. These materials emerged as a highly active visible light-driven photocatalyst towards degradation of methylene blue dye and the efficiencies are dependent on size and surface area of the NPs. In addition, photocatalytic degradation of highly toxic dichlorodiphenyltrichloroethane was studied using synthesized Bi2S3 NPs as catalyst and the rate of degradation has been found to be much better compared to that exhibited by commercial WO3. We believe that this new synthesis approach can be extended to the synthesis of other metal sulfide nanostructures and open new opportunities for device applications. PMID- 27552414 TI - Cubic KTi2(PO4)3 as electrode materials for sodium-ion batteries. AB - A novel cubic KTi2(PO4)3 is successfully synthesized via a facile hydrothermal method combined with a subsequent annealing treatment and further used as electrode material for sodium-ion batteries for the first time. For comparison, carbon-coated KTi2(PO4)3 obtained by a normal cane sugar-assisted method reveals superior electrochemical performances in sodium-ion battery. Besides of the high coulombic efficiency of nearly 100% after 100 cycles, a stable capacity of 112mAhg(-1) can be achieved at 0.5C after 100 cycles, and still maintains to 105mAhg(-1) after 500 cycles with capacity retention of approximately 90%. PMID- 27552415 TI - Mesoporous transition metal oxides quasi-nanospheres with enhanced electrochemical properties for supercapacitor applications. AB - In this report, we obtain mesoporous transition metal oxides quasi-nanospheres (includes MnO2, NiO, and Co3O4) by utilizing mesoporous silica nanospheres as a template for high-performance supercapacitor electrodes. All samples have a large specific surface area of approximately 254-325m(2)g(-1) and a relatively narrow pore size distribution in the region of 7nm. Utilization of a nanosized template resulted in a product with a relative uniform morphology and a small particle diameter in the region of 50-100nm. As supercapacitor electrodes, MnO2, NiO, and Co3O4 exhibit an outstanding capacity as high as 838-1185Fg(-1) at 0.5Ag(-1) and a superior long-term stability with minimal loss of 3-7% after 6000 cycles at 1Ag(-1). Their excellent electrochemical performances are attributed to favorable morphologies with a large surface area and a uniform architecture with abundant pores. The associated enhancement of electrolyte ion circulation within the electrode facilitates a significant increase in availability of Faradic reaction electroactive sites. PMID- 27552416 TI - Tailoring barrier properties of thermoplastic corn starch-based films (TPCS) by means of a multilayer design. AB - This work compares the effect of adding different biopolyester electrospun coatings made of polycaprolactone (PCL), polylactic acid (PLA) and polyhydroxybutyrate (PHB) on oxygen and water vapour barrier properties of a thermoplastic corn starch (TPCS) film. The morphology of the developed multilayer structures was also examined by Scanning Electron Microscopy (SEM). Results showed a positive linear relationship between the amount of the electrospun coatings deposited onto both sides of the TPCS film and the thickness of the coating. Interestingly, the addition of electrospun biopolyester coatings led to an exponential oxygen and water vapour permeability drop as the amount of the electrospun coating increased. This study demonstrated the versatility of the technology here proposed to tailor the barrier properties of food packaging materials according to the final intended use. PMID- 27552417 TI - Design of a highly photocatalytically active ZnO/CuWO4 nanocomposite. AB - Here we report the synthesis, photocatalytic activity and mechanistic study of a novel charge separation heterostructure (HTS). A ZnO/CuWO4 HTS material is reported for the first time. The nanocomposite (NC) consist of CuWO4 nanoparticles (ca. 200-400nm) decorated with ZnO nanorods (ca. 30nm, 100nm length) and is shown to be a highly active photocatalyst for the decomposition of model contaminants including methyl orange (MO) and terephthalic acid (TPA). The ZnO/CuWO4 interface is shown to be key in controlling the enhanced activity of the composite material. Transient absorption (TA) spectroscopy studies demonstrate that photoinduced charge transfer across the ZnO/CuWO4 interface increases electron-hole lifetimes by 3 orders of magnitude, from <20MUs in ZnO to 30ms in the ZnO/CuWO4 NC sample. Our findings show that through interface design efficient HTS materials can be prepared for a wide range of photocatalytic applications. PMID- 27552418 TI - Competitive adsorption desulfurization performance over K - Doped NiY zeolite. AB - NiY and KNiY were successfully prepared by impregnation method and characterized by X-ray diffraction (XRD), N2 sorption (BET), scanning electron microscope (SEM), infrared spectrum (IR) and X-ray Photoelectron Spectroscopy (XPS). The competitive adsorption mechanisms of adsorbents were studied by in situ FTIR to explain different desulfurization performance which was evaluated in a miniature fixed-bed flow by gasoline model compounds with 1-hexene or toluene. NiY and KNiY adsorbents showed better desulfurization performance than HY zeolite due to the high selectivity of loaded active metals. Especially, KNiY adsorbent showed its advantages in desulfurization performance with 5vol% olefins or 5vol% aromatics involvement. It could be assigned that introduced K cation enhanced dispersion and content of active Ni species on the surface which made Ni species reduce easily. On the other hand, adsorption mechanisms showed that the protonation reactions of thiophene and 1-hexene occurred on the Bronsted acid sites of NiY, which resulted in pore blockage and the coverage of adsorption active centers. By doping K cation on NiY, the amount of the Bronsted acid sites of NiY was decreased and protonation reactions were weaken. Therefore, the negative effects of Bronsted acid sites were reduced. PMID- 27552419 TI - Electrochemical properties of the acetaminophen on the screen printed carbon electrode towards the high performance practical sensor applications. AB - Acetaminophen is a non-steroidal anti-inflammatory drug used as an antipyretic agent for the alternative to aspirin. Conversely, the overdoses of acetaminophen can cause hepatic toxicity and kidney damage. Hence, the determination of acetaminophen receives much more attention in biological samples and also in pharmaceutical formulations. Here, we report a rapid and sensitive detection of the acetaminophen based on the bare (unmodified) screen printed carbon electrode (BSPCE) and its electrochemistry was studied in various pHs. From the observed results, the mechanism of the electro-oxidation of acetaminophen was derived for various pHs. The acetaminophen is not stable in strong acidic and strong alkaline media, which is hydrolyzed and hydroxylated. However, it is stable in intermediate pHs due to the dimerization of acetaminophen. The kinetics of the acetaminophen oxidation was briefly studied and documented in the schemes. In addition, the surface morphology and disorders of BSPCE was probed by scanning electron microscope (SEM) and Raman spectroscopy. Moreover, the BSPCE determined the acetaminophen with the linear concentration ranging from 0.05 to 190MUM and the lower detection limit of 0.013MUM. Besides that it reveals the good recoveries towards the pharmaceutical samples and shows the excellent selectivity, sensitivity and stability. To the best of our knowledge, this is the better performance compare to the previously reported unmodified acetaminophen sensors. PMID- 27552420 TI - Adsorption of methyl orange and salicylic acid on a nano-transition metal composite: Kinetics, thermodynamic and electrochemical studies. AB - In this work synthesis of Mn-nanoparticles (MnNPs) supported on the Schiff base modified nano-sized SiO2Al2O3 mixed-oxides (Si/Al) and its implementation as an adsorbent for the removal of organic pollutions such as methyl orange (MO) and salicylic acid (SA) was investigated. Si/Al were functionalized by grafting Schiff base ligand and in the next step, MnNPs were prepared over the modified nano sol-gel Si/Al. Structures and adsorption characteristics of the obtained organometallic-modified SiO2/Al2O3 mixed oxide were studied by several methods such as elemental analysis, diffuse reflectance UV-vis spectroscopy, FT-IR spectroscopy, nitrogen adsorption/desorption, scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive X-ray (EDX), inductively coupled plasma (ICP-AES), Electron Paramagnetic Resonance (EPR), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). EPR data of the immobilized manganese ions resulted that the transition state of active sites in the nano-adsorbent are in the form of Mn(II) ions at the surface. The adsorption properties of heterogeneous Mn(II) ions showed that this nano adsorbent has very good potential to remove MO and SA ions from aqueous solution. The removal efficiency of the SAPAS@MnNPs towards MO reached out to 89.3 and 29.1% and for SA approached to 54.6 and 18.9% at 150 and 500mg/dm(3) initial organic pollution concentrations, respectively. To investigate the adsorption kinetic of Mn(II) ions onto the nano-sized support, pseudo first and pseudo second order kinetics, and the Freundlich, Langmuir and Langmuir-Freundlich isotherm models have also been applied to the equilibrium adsorption data. The contact time to obtain equilibrium for maximum adsorption capacity was 45min. The adsorption process was spontaneous and endothermic in nature and it was well explained with pseudo-second-order kinetic model. No remarkable loss of removal capacity even after 8th times regeneration was obtained, implying that the immobilized MnNPs has high solidity through the regeneration process. Finally, the mechanism of the MO adsorption process as a model has been studied by the CV, EIS and FTIR techniques. The electrochemical results showed that the oxidation of Mn(II) was easier and took place at lower potentials in the presence of MO, where the electron density at SAPAS@MnNP is higher, consequently reduction of Mn(III) to Mn(II) is more favored. These results suggest that the surface of SAPAS@MnNP was interacted and complexed by MO therefore accelerates electron transfer rate of the reaction related to Mn(II)/Mn(III) redox couple. PMID- 27552422 TI - Using Eu(3+) as an atomic probe to investigate the local environment in LaPO4 GdPO4 monazite end-members. AB - In the present study, we have investigated the luminescent properties of Eu(3+) as a dopant in a series of synthetic lanthanide phosphates from the monazite group. Systematic trends in the spectroscopic properties of Eu(3+) depending on the size of the host cation and the dopant to ligand distance have been observed. Our results show that the increasing match between host and dopant radii when going from Eu(3+)-doped LaPO4 toward the smaller GdPO4 monazite decreases both the full width at half maximum of the Eu(3+) excitation peak, as well as the (7)F2/(7)F1 emission band intensity ratio. The decreasing Ln?O bond distance within the LnPO4 series causes a systematic bathochromic shift of the Eu(3+) excitation peak, showing a linear dependence of both the host cation size and the Ln?O distance. The linear relationship can be used to predict the energy band gap for Eu(3+)-doped monazites for which no Eu(3+) luminescent data is available. Finally, mechanisms for metal-metal energy transfer between host and dopant lanthanides have been explored based on recorded luminescence lifetime data. Luminescence lifetime data for Eu(3+) incorporated in the various monazite hosts clearly indicated that the energy band gap between the guest ion emission transition and the host ion absorption transition can be correlated to the degree of quenching observed in these materials with otherwise identical geometries and chemistries. PMID- 27552421 TI - Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in vitro, in-vivo evaluation. AB - The current research focuses on developing positively charged gelatin nanoparticles loaded with moxifloxacin for its effective ocular delivery and controlled release in corneal eye layer. We selected type A gelatin because of its biodegradable and non-toxic nature as the polymer of choice for fabricating the nanoparticles by a modified two step desolvation technique. The produced nanoparticles were positively charged (+24+/-0.12mV) with a narrow particle size of 175+/-1.11nm as measured by dynamic light scattering (DLS). The in-vitro drug release from the nanoformulations exhibited a burst effect in the first hour followed by a controlled release of the drug for the subsequent 12h. The Korsmeyer-Peppas model showed better linearity and the formulations displayed non Fickian drug release pattern. The optimized formulation was assessed for its utility as an anti-bacterial agent and its effectiveness was tested on the corneal eye surface of rabbits. The in-vivo tolerance tests revealed that the drug loaded nano-formulations was non-irritant to the ocular tissues indicating its safety. The in-vivo anti-bacterial activity of the nanosuspension was more effective against S. aureus than the commercially market product, MoxiGram(r). Microbiological efficacy assessed against B. subtilus using cup-plate method suggested that our fabricated nanosuspension possess better anti-microbial activity as compared to the commercial agent, MoxiGram(r) revealing promising potentials for the currently developed gelatin based nanoformualtions. PMID- 27552423 TI - Synthesis of novel AuPd nanoparticles decorated one-dimensional ZnO nanorod arrays with enhanced photoelectrochemical water splitting activity. AB - The vertically aligned one-dimensional (1D) ZnO nanorod arrays decorated with AuPd alloy nanoparticles have been synthesized with ZnO nanorod arrays as template via a mild hydrothermal method. In this work, the as-prepared AuPd/ZnO nanorod arrays demonstrated high light-harvesting efficiency. The microstructures, morphologies and chemical properties of the obtained AuPd/ZnO composite photocatalyst were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis diffuse reflectance spectra (DRS) and X-ray photoelectron spectroscopy (XPS). The photoelectrochemical (PEC) performances of as-obtained AuPd/ZnO nanorod arrays were examined, and the photocurrent density was up to 0.98mAcm(-2) at 0.787V versus Ag/AgCl, which was about 2.4 times higher than the pure ZnO sample. A possible photocatalytic mechanism of the AuPd/ZnO hybrid nanostructures under the simulated sunlight irradiation was proposed to guide further improvement of other desirable materials. According to the above experiment results, it can be clearly found that AuPd/ZnO composite nanorod arrays showed excellent PEC performance and had promising applications in the utilization of solar energy. PMID- 27552424 TI - The effects of intermolecular interactions on the physical properties of organogels in edible oils. AB - The microstructure of organogels based on monoglycerides of fatty acids (MAGs) and policosanol and on different edible oils was investigated by using different techniques (calorimetry, nuclear magnetic resonance, infrared spectroscopy, rheology, polarized light microscopy) towards a better understanding and control of the oil gelation phenomena. Dynamic moduli were related via a fractal model to microstructural information such as solid content and fractal dimension. Infrared spectroscopy evidenced that network structure in MAGs gel is mainly due to hydrogen bonding, whereas in policosanol system is mainly given by van der Waals interactions. Because of the different relative contribution of molecular interactions, the investigated organogelators exhibit a distinguished macroscopic behavior. MAGs are sensitive to the utilized oil and structuration occurs quickly, even though at a temperature lower than policosanol. Policosanol organogels exhibit a behavior independent of the used oil and a slower gelation rate, as a result of the weaker van der Waals interactions. Nevertheless, at lower concentration a stronger final gel is obtained, probably due to of the large number of interactions arising among the long alkyl chains of the fatty alcohols. Obtained results evidenced that policosanol is very effective in gelation of different oils and seems promising for potential commercial uses. PMID- 27552425 TI - Decoupling and elucidation of surface-driven processes during inorganic mineralization on virus templates. AB - There is a lack of fundamental information about the molecular processes governing biomineralization of inorganic materials to produce nanostructures on biological templates. This information is essential for the directed synthesis of high quality nanomaterials via biotemplating. We characterized palladium (Pd) mineralization via the individual adsorption, reduction, and nanocrystal growth processes, which simultaneously occur during the hydrothermal synthesis on the Tobacco mosaic virus (TMV). The adsorption of precursor and reduction of palladium were decoupled through UV-vis Spectroscopy and in situ X-ray absorption spectroscopy studies. The role of additional cysteine (Cys) residues, ionic strength, and coating density on the fundamental parameters describing these processes were quantitatively evaluated. Primary nanocrystal growth and structural orientation of Pd nanoparticles was characterized using in situ small angle X-ray scattering. The adsorption, reduction of Pd species, and nanocrystal sizes were significantly changed on addition of Cys residues to the amino terminus of the TMV coat protein. Reduction of Pd on an already coated virion was dependent on the Pd surface area, and was hindered by the presence of residual salt. Furthermore, trends in Pd adsorption intensity and capacity suggested that chloride ions affected the adsorption equilibrium. Application of this fundamental approach with further optimization of parameters dictating biomineralization would facilitate directed synthesis and scale up of bioinorganic systems. PMID- 27552426 TI - Size-dependent interactions of silica nanoparticles with a flat silica surface. AB - We have investigated the surface chemistry of SiO2 nanoparticles (NPs) with different sizes and their corresponding interactions with a flat substrate of surface curvature ~0. As the size of the NPs increases, the SiO2 surface is increasingly covered with H-bonded silanol groups, thereby increasing the zeta potential and shifting the isoelectric point higher in pH. Interactions between the SiO2 NPs and the flat SiO2 surface were analyzed in situ using quartz crystal microbalance with dissipation (QCM-D) method, and the results were interpreted based on an extended Derjaguin-Landau-Verwey-Overbeek theory. At very low ionic strength (1mM NaCl), there was no particle adsorption onto the surface due to the highly repulsive energy barriers to this interaction. On the other hand, QCM-D results showed that the significant adsorption of SiO2 NPs onto a flat SiO2 surface occurred under conditions of high ionic strength (100mM NaCl). Interestingly, the adsorption behaviors of three different-sized SiO2 NPs on the surface varied considerably with size. SiO2 NPs with small size have high adsorption affinity with the flat SiO2 surface due to an extremely low energy barrier for the interactions, whereas relatively large SiO2 NPs have very weak adsorption affinity with the flat surface due to the repulsive energy barrier formed by the increase in the electrostatic and hydration repulsion energy. PMID- 27552427 TI - Synthesis and application of a new carboxylated cellulose derivative. Part I: Removal of Co(2+), Cu(2+) and Ni(2+) from monocomponent spiked aqueous solution. AB - A new carboxylated cellulose derivative (CTA) was prepared from the esterification of cellulose with 1,2,4-Benzenetricarboxylic anhydride. CTA was characterized by percent weight gain (pwg), amount of carboxylic acid groups (nCOOH), elemental analysis, FTIR, TGA, solid-state (13)C NMR, X-ray diffraction (DRX), specific surface area, pore size distribution, SEM and EDX. The best CTA synthesis condition yielded a pwg and nCOOH of 94.5% and 6.81mmolg(-1), respectively. CTA was used as an adsorbent material to remove Co(2+), Cu(2+) and Ni(2+) from monocomponent spiked aqueous solution. Adsorption studies were developed as a function of the solution pH, contact time and initial adsorbate concentration. Langmuir model better fitted the experimental adsorption data and the maximum adsorption capacities estimated by this model were 0.749, 1.487 and 1.001mmolg(-1) for Co(2+), Cu(2+) and Ni(2+), respectively. The adsorption mechanism was investigated by using isothermal titration calorimetry. The values of DeltaadsH degrees were in the range from 5.36 to 8.09kJmol(-1), suggesting that the mechanism controlling the phenomenon is physisorption. Desorption and re adsorption studies were also performed. Desorption and re-adsorption efficiencies were closer to 100%, allowing the recovery of both metal ions and CTA adsorbent. PMID- 27552429 TI - Multifunctional catalysts based on carbon nanotubes and titanate nanotubes for oxidation of organic compounds in biphasic systems. AB - Amphiphilic catalysts composed of carbon nanotubes (CNTs) and titanate nanotubes (TiNTs) have been successfully synthesized by refluxing anatase TiO2 and functionalised CNTs in concentrated NaOH solution. The prepared materials were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis (TGA), and N2 physisorption isotherms. The catalytic activity of the synthesized composites was first evaluated in the oxidation of methyl yellow (MY) using H2O2 as oxidant in a single liquid phase system and in a biphasic water/oil mixture. The results of these experiments indicated that the catalytic activities of nanocomposites were very similar in the single liquid-phase oxidation. However, the modification of TiNTs with CNTs led to a substantially enhanced MY oxidation in the biphasic system. The nanocomposites show excellent interaction with both hydrophilic and hydrophobic compounds and thus stabilise emulsions. Under biphasic conditions, the catalysts can be easily separated and recycled, retaining catalytic activity even after eight runs. Additionally, the hybrid materials show superior catalytic activity and selectivity in the biphasic oxidation of benzyl alcohol with H2O2, as compared to pure TiNTs. PMID- 27552430 TI - Highly selective and sensitive response of 30.5 % of sprayed molybdenum trioxide (MoO3) nanobelts for nitrogen dioxide (NO2) gas detection. AB - The molybdenum trioxide (MoO3) thin films have been successfully deposited onto the glass substrates using chemical spray pyrolysis (CSP) deposition technique at various substrate temperatures ranging from 300 degrees C to 450 degrees C with an interval of 50 degrees C. The effect of substrate temperature on the structural, morphological, optical and gas sensing properties of MoO3 thin films has been thoroughly investigated. X-ray diffraction analysis reveals that all the films have an orthorhombic crystal structure and are polycrystalline in nature. FE-SEM micrographs depict the formation of nanobelts-like morphology. AFM study reveals that the RMS surface roughness of MoO3 thin films increases from 8.6nm to 12nm with increase in substrate temperature from 300 degrees C to 400 degrees C and then decreases to 11.5nm for substrate temperature of 450 degrees C. Optical results show that the band gap of MoO3 thin films decreases from 3.92eV to 3.44eV. The selectivity studies show that the gas response of various gases varies as NH3 .05). We did not find an association between persistence of VP and pseudarthrosis. Persistence of VP after spinal fusion may not be an indicator of pseudarthrosis, and should not be misinterpreted as an indication for additional surgery. PMID- 27552462 TI - High-Grade Articular, Bursal, and Intratendinous Partial-Thickness Rotator Cuff Tears: A Retrospective Study Comparing Functional Outcomes After Completion and Repair. AB - We conducted a study to assess the impact of tear location on functional outcomes in high-grade partial-thickness rotator cuff tears (PTRCTs) after arthroscopic completion and repair. Retrospectively, we evaluated the preoperative and postoperative findings of 60 patients who underwent arthroscopic completion and repair of Ellman grade 3 partial-thickness tears of the supraspinatus. The 60 patients were grouped by tear subtype (20 articular, 20 bursal, 20 intratendinous) as identified by preoperative imaging and confirmed at time of surgery. After surgery, the 3 subtypes showed similar significant (P < .001) improvements in American Shoulder and Elbow Surgeons scores (articular, 46.9, 85.1; bursal, 44.3, 80.3; intratendinous, 43.6, 86.1), Constant scores (articular, 54.3, 79.4; bursal, 49.9, 75.0; intratendinous, 56.8, 80.9), and visual analog scale scores (articular, 5.1, 1.2; bursal, 5.8, 1.6; intratendinous, 6.0, 1.2). Our study findings validate use of the current algorithm for Ellman grade 3 PTRCTs of the supraspinatus and advocate their completion and repair, regardless of tear location. PMID- 27552464 TI - Biomechanical Consequences of Anterior Femoral Notching in Cruciate-Retaining Versus Posterior-Stabilized Total Knee Arthroplasty. AB - Anterior femoral notching during total knee arthroplasty is a potential risk factor for periprosthetic supracondylar femur fracture. We conducted a study to determine if the design of the femoral implant changes the risk for periprosthetic supracondylar femur fractures after anterior cortical notching. An anterior cortical defect was created in 12 femoral polyurethane models. Six femora were instrumented with cruciate-retaining implants and 6 with posterior stabilized implants. Each femur was loaded in external rotation along the anatomical axis. Notch depth and distance from anterior cortical notch to implant were recorded before loading, and fracture pattern was recorded after failure. There were no statistically significant differences in notch depth, distance from notch to implant, torsional stiffness, torque at failure, final torque, or fracture pattern between cruciate-retaining and posterior-stabilized femoral component designs. Periprosthetic fracture after anterior femoral notching is independent of the bone removed from the intercondylar notch. After notching, there likely is no significant difference in femoral strength in torsion between cruciate-retaining and posterior-stabilized designs. PMID- 27552463 TI - Biomechanical Evaluation of Two Arthroscopic Biceps Tenodesis Techniques: Proximal Interference Screw and Modified Percutaneous Intra-Articular Transtendon. AB - The percutaneous intra-articular transtendon (PITT) technique has recently been shown to have results comparable to those of more accepted techniques. Its mode of failure was secondary to the suture pulling through the tendon substance. A modification was made whereby the tendon is locked within the suture configuration in an attempt to avoid pullout. We compared this new technique with a well-accepted technique of all-arthroscopic interference screw. In each of 8 pairs of cadaveric shoulders (mean age, 55 years; range, 51-59 years), one shoulder was randomized to be treated with either modified PITT or interference screw (Biceptor; Smith & Nephew) biceps tenodesis, and the other shoulder was treated with the other technique. The tendons were preloaded at 10 N and then cycled at 0 to 50 N for 100 cycles at 1 Hz. Load to failure was calculated at a rate of 1.0 mm per second until peak load was observed. Mean (SD) ultimate load to failure was 157 (41) N for the modified PITT technique and 107 (29) N for the interference screw technique (P = .003). In 7 of 8 specimens, the interference screw technique failed at the junction of the tendon, the screw, and the bone interface. In 7 of 8 specimens, the PITT technique failed by the tendon slipping through the suture or pulling through transverse ligament/rotator interval tissue. Study results showed the modified PITT technique was a biomechanically superior construct. PMID- 27552465 TI - Clinical Outcomes of Anatomical Total Shoulder Arthroplasty in a Young, Active Population. AB - Glenohumeral arthritis in young, active patients poses many treatment challenges, and significant concerns about component loosening and failure limit the available surgical options. We conducted a study of the clinical outcomes of total shoulder arthroplasty (TSA) for glenohumeral arthritis in a young, high demand population. We searched the Military Health System Management Analysis and Reporting Tool database to retrospectively review the cases of all US military service members who had undergone anatomical TSA (Current Procedural Terminology code 23472) between 2007 and 2014. Demographic information, occupational parameters, and clinical outcomes were extracted from electronic medical records. Twenty-four service members (26 shoulders) met the inclusion criteria. The cohort was predominantly male (n = 25). Mean age was 45.8 years (range, 35-54 years). The most common etiology of glenohumeral arthritis was post-instability arthropathy (50.0%). At mean follow-up of 41 months, 9 patients had a total of 12 complications (46.2%), including 6 component failures caused by neurologic injury (2 cases), adhesive capsulitis (2), and venous thrombosis (2). The reoperation rate for all component failures was 23.1% (6 cases, 5 patients). Ten patients (41.7%) remained on active duty at 2 years, and 5 (20.8%) were subsequently deployed. Ultimately, 9 patients (37.5%) underwent medical discharge for persistent shoulder disability. TSA in young, active patients provides reliable improvements in range of motion and pain. However, roughly one-third of patients in this study were unable to continue high-demand activities by 2 years after surgery. The short-term complication profile (46.2%) and reoperation rate for component failure (23.1%) should be emphasized during preoperative counseling. PMID- 27552466 TI - Clinical and Sonographic Evaluation of Bicortical Button for Proximal Biceps Tenodesis. AB - Use of a cortical button for proximal biceps tenodesis has demonstrated strength comparable to that of other types of fixation in biomechanical models, but few studies have evaluated the clinical outcome of such fixation. In the study reported here, 18 patients who underwent open subpectoral biceps tenodesis with a bicortical button were assessed, at minimum 12-month follow-up, with the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, a pain scale, physical examination, biceps supination strength testing, and ultrasonographic evaluation (to determine tenodesis integrity and proximity of the button to the axillary nerve). No patient had symptoms of axillary nerve damage, clinical deformity, or tenodesis failure. Mean DASH score was 15.15 (scale range: 0, none to 100, extreme difficulty), and mean pain score was 12.6 (scale range: 0, none to 100, worst pain). Seventy-eight percent of patients had no bicipital groove tenderness, 89% had full elbow range of motion, and 94% had full shoulder range of motion. Mean forearm supination strength of the operated arm (125.04 lb) was significantly (P = .01) less than that of the nonoperated arm (134.39 lb). Mean (SD) distance from button to posterior circumflex humeral artery was 18.17 (9.0) mm. The study results suggest that subpectoral biceps tenodesis with a bicortical button is a safe, stable procedure that results in excellent functional outcomes. PMID- 27552467 TI - Quality and Quantity of the Elbow Arthroscopy Literature: A Systematic Review and Meta-Analysis. AB - The purpose of this article is to perform a systematic review and meta-analysis of elbow arthroscopy literature to answer the following questions: "Across the world, what demographic of patients are undergoing elbow arthroscopy, what are the most common indications for elbow arthroscopy, and how good is the evidence?" The authors hypothesized that patients who undergo elbow arthroscopy will be chiefly age <40 years, the most common indication for elbow arthroscopy will be a release/debridement, and the evidence regarding elbow arthroscopy will be poor. Also, no significant differences will exist in elbow arthroscopy publications, subjects, outcomes, and techniques based on continent/country of publication. A systematic review was registered with the International Prospective Register of Ongoing Systematic Reviews (PROSPERO) and performed with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using 3 publicly available databases. Therapeutic clinical outcome investigations reporting arthroscopic elbow outcomes with levels of evidence I-IV were eligible for inclusion. All study, subject, and surgical technique demographics were analyzed and compared between continents and countries. Statistics were calculated using 1-way analysis of variance (ANOVA) to compare between continents and Pearson's correlation coefficients to evaluate changes over time. In total, 112 studies were included (3093 subjects; 3168 elbows; 64% male; mean 34.9 +/- 14.68 years. Mean 33.4 +/- 26.02 months follow-up. Most studies were level IV evidence (94.6%) and had a low Modified Coleman Methodology Score (MCMS) (mean 28.1 +/- 8.06). From 1985 through 2013, the number of publications significantly increased with time (P = .004) in all continents. The 3 most common indications for elbow arthroscopy were osteochondritis dissecans (OCD), lateral epicondylitis, and release and debridement. The number of reported cases for the 3 most common indications significantly increased over time but did not differ between regions (P > .05 in all cases). Thirty-two studies (28.6%) reported clinical outcomes, the most common of which was the Mayo Elbow Performance Score, reported in 9.8% of studies. The quantity, but not the quality, of arthroscopic elbow publications has significantly increased over time. Most patients undergo elbow arthroscopy for lateral epicondylitis, OCD, and release and debridement. Pathology and indications do not appear to differ geographically with more men undergoing elbow arthroscopy than women. PMID- 27552468 TI - Prevention of Periprosthetic Joint Infections of the Hip and Knee. AB - Periprosthetic joint infection (PJI) is a rare but devastating complication of arthroplasty. Research has been dedicated to minimizing the incidence of PJI, leading to the development of a comprehensive perioperative approach. Multiple preoperative, intraoperative, and postoperative factors can increase patient risk. From medical management and skin sterilization to wound sterility and blood management, multiple issues must be considered in a well-rounded prevention protocol. In this literature review, we consolidate the current information that orthopedic surgeons can use to minimize PJI after total knee arthroplasty and total hip arthroplasty. PMID- 27552469 TI - Child Maltreatment as a Root Cause of Mortality Disparities: A Call for Rigorous Science to Mobilize Public Investment in Prevention and Treatment. PMID- 27552471 TI - Depressive symptoms across the menopause transition: findings from a large population-based cohort study. AB - OBJECTIVE: The aim of the study was to describe the trajectories of depressive symptoms in a large population-based cohort of midaged women, and to examine the associations of current and changing reproductive stage with depressive symptoms over time. METHODS: Prospective, population-based cohort study of 13,715 women aged 45 to 50 years followed up for over 15 years (Australian Longitudinal Study on Women's Health). Nearly 6,000 women provided complete data for this study. Menopause status was determined from questionnaires about hysterectomy, oophorectomy, hormone therapy, and menstrual patterns. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression scale (CESD-10). RESULTS: Latent class analysis indicated four distinct profiles of CESD-10 scores over 15 years: stable low (80.0%), increasing (9.0%), decreasing (8.5%), and stable high (2.5%). Those with "increasing" depressive symptoms were more likely to have had bilateral salpingo-oophorectomy or be perimenopausal at baseline compared with women in the "stable low" group. Depressive symptoms were higher in perimenopausal women, (higher CESD-10 score of 0.19, 95% CI 0.02, 0.31), after hysterectomy alone (0.53, 95% CI 0.31, 0.74), bilateral salpingo-oophorectomy with/without hysterectomy (0.85, 95% CI 0.58, 1.12), hormone therapy users (0.19, 95% CI 0.01, 0.36), and after starting or stopping hormone therapy compared with postmenopausal women (adjusted for sociodemographic factors, vasomotor symptoms, health behaviors, and history of depression diagnosis or treatment). CONCLUSIONS: Depressive symptoms follow distinct trajectories across the menopause transition. Most women have stable symptoms, but around 9% have increasing symptoms and a similar proportion (8.5%) decreasing symptoms. Increasing depressive symptoms were independent of vasomotor symptoms but were associated with oophorectomy and stopping or starting hormone therapy. A large number of women were excluded due to missing data, and thus the results should be interpreted with caution. PMID- 27552472 TI - Sexual and reproductive healthcare utilization among women aged 40 to 49 in rural China. AB - OBJECTIVE: China's national family planning system is mainly directed toward women of early reproductive ages. Most studies of service provision focused on younger women, who almost all receive regular examinations. Little is known about service-seeking behavior among women of late reproductive ages. METHODS: This cross-sectional household survey interviewed 1,811 rural women aged 40 to 49 in seven provinces. We examined sexual and reproductive health, utilization of sexual and reproductive health services, and predictors of receiving a free gynecological examination in the past 2 years. RESULTS: Educational levels were not high, and most women were rural farmers or housewives. More than one-fourth had migrated for work to big cities when they were younger. The mean frequency of sex in the last month was 3.6 times. Approximately 22.7% of women had not received a gynecological examination and 31.2% had not received any health education during the past 2 years. The first choice for where to seek services was township medical facilities (58.4%). On multivariate regression, age, education, migrant working experience, awareness of the need for intrauterine device removal after menopause, health education received, and attitude toward health examinations were significantly associated with receiving a gynecological examination in the past 2 years. CONCLUSIONS: Women of late reproductive age in rural China are not receiving as regular care as younger women. This study identifies sociodemographic and health service correlates for service-seeking behavior, many of which are modifiable. Health services should pay greater attention to this group, including community-based efforts to encourage routine examinations and appropriate use of health services. PMID- 27552470 TI - Evaluation of the potential antidepressant effects of soybean isoflavones. AB - OBJECTIVE: The aim of the study was to determine whether isoflavones affect depressive symptoms in women. METHODS: Literature searches were conducted to identify clinical and epidemiologic studies that evaluated the impact of soy intake and isoflavone exposure on depressive symptoms. References from identified studies were also evaluated to identify eligible studies. RESULTS: Only limited epidemiologic research has evaluated the impact of soy or isoflavone intake on depression although several studies from China and Japan did find soy product intake was inversely related to risk of depression. Often times, soy was, however, evaluated only as a component of a summative dietary pattern (eg, a "Japanese" or "Healthy" diet). Of the 20 intervention studies identified, roughly half found statistically significant reductions in depressive symptoms in response to isoflavones although several had design weakness. Of those studies reporting a lack of antidepressant effects of isoflavones, design limitations likely contributed to the lack of efficacy. In all but two trials, assessment of depression was, however, a secondary outcome. It is notable that both trials in which depression was a primary outcome found isoflavones significantly improved symptoms. CONCLUSIONS: Although the data are inconsistent and limited, the clinical and epidemiologic evidence suggests that isoflavones may offer a safe, well-tolerated option for management of depression. Furthermore, the intervention doses used in the clinical studies fall well within the dietary range. The extant literature reveals key design features for future studies, which based upon the results of this review, are clearly warranted. PMID- 27552473 TI - Lean, but not healthy: the 'metabolically obese, normal-weight' phenotype. AB - PURPOSE OF REVIEW: Obesity is commonly associated with metabolic dysfunction but there are obese persons who are metabolically healthy. On the opposite side of the coin, there are lean persons who carry multiple cardiometabolic risk factors, typically referred to as metabolically obese, normal-weight (MONW). This has called into question our understanding of obesity and metabolic dysfunction, as an appearance of normal weight may mask significant comorbidities and delay health interventions. RECENT FINDINGS: High heterogeneity in MONW prevalence rates has been observed, with estimates ranging from as low as 5% to as high as 45%. Reasons for this include sample size effects, differences in MONW definition, social and demographic factors, as well as assumptions made in establishing normal weight. MONW study participants are often characterized by excess visceral adipose tissue and ectopic fat deposition, adipose tissue inflammation, altered inflammatory and adipokine profiles, reduced skeletal muscle mass and low cardiorespiratory fitness. However, more often than not, groups of MONW study participants have been somewhat 'fatter' than the control groups of metabolically healthy lean study participants, which in itself could be responsible for some of the observed differences. Very limited data are available regarding interventions to improve metabolic function in MONW study participants. SUMMARY: There is a need for more research to better understand the characteristics of the MONW phenotype, the cause of metabolic dysfunction in the absence of obesity, and evaluate potential therapies so as to facilitate the establishment of clinical guidelines. PMID- 27552474 TI - Potential harmful effects of dietary supplements in sports medicine. AB - PURPOSE OF REVIEW: The purpose of this article is to collect the most recent data regarding the safety of well-known or emerging dietary supplements used by athletes. RECENT FINDINGS: From January 2014 to April 2016, about 30 articles have been published in the field. New data show that 90% of sports supplements contain trace of estrogenic endocrine disruptors, with 25% of them having a higher estrogenic activity than acceptable. About 50% of the supplements are contaminated by melamine, a source of nonprotein nitrogen. Additional data accumulate toward the safety of nitrate ingestion. In the last 2 years, the safety of emerging supplements such as higenamine, potentially interesting to lose weight, creatine nitrate and guanidinoacetic acid has been evaluated but still needs further investigation. SUMMARY: The consumption of over-the-counter supplements is very popular in athletes. Although most supplements may be considered as safe when taking at the recommended doses, athletes should be aware of the potential risks linked to the consumption of supplements. In addition to the risks linked to overdosage and cross-effects when combining different supplements at the same time, inadvertent or deliberate contamination with stimulants, estrogenic compounds, diuretics or anabolic agents may occur. PMID- 27552475 TI - Towards a multidimensional healthy ageing phenotype. AB - PURPOSE OF REVIEW: There is great interest in developing tools to measure healthy ageing and to identify early stages of health impairment, which may guide the implementation of interventions to prevent or delay the development of disease, disability, and mortality. Here, we review the most recent developments directed to operationalize, and test, definitions of healthy ageing. RECENT FINDINGS: There is lack of consensus about how to define healthy ageing and, unsurprisingly, diversity in the instruments for its measurement. However, progress is being made in describing and in devising tools to capture the healthy ageing phenotype. Attempts to measure healthy ageing have relied primarily on cross-sectional data collected in older people. More recent studies have assessed the healthy ageing phenotype using markers of multiple functional domains and have used longitudinal data to model the dynamics and trajectories of healthy ageing. SUMMARY: Given the complexity of the ageing process, no single measure is able to predict the ageing trajectory. Current attempts to operationalize the healthy ageing phenotype have relied on markers and data from earlier cohort studies and are limited by the tools used to collect data in those studies. Such data are often unsuitable to detect early subtle declines in function and/or are inappropriate for use in younger old adults. Future studies employing more objective and novel markers of healthy ageing are likely to offer opportunities to define and operationalize the healthy ageing phenotype. PMID- 27552476 TI - Mediterranean diet and life expectancy; beyond olive oil, fruits, and vegetables. AB - PURPOSE OF REVIEW: The recent relevant evidence of the effects of the Mediterranean diet (MedDiet) and lifestyle on health (2015 and first months of 2016). RECENT FINDINGS: Large observational prospective epidemiological studies with adequate control of confounding and two large randomized trials support the benefits of the Mediterranean dietary pattern to increase life expectancy, reduce the risk of major chronic disease, and improve quality of life and well-being. Recently, 19 new studies from large prospective studies showed - with nearly perfect consistency - strong benefits of the MedDiet to reduce the risk of myocardial infarction, stroke, total mortality, heart failure, and disability. Interestingly, two large and well conducted cohorts reported significant cardiovascular benefits after using repeated measurements of diet during a long follow-up period. In addition, Prevencion con Dieta Mediterranea, the largest randomized trial with MedDiet, recently reported benefits of this dietary pattern to prevent cognitive decline and breast cancer. SUMMARY: In the era of evidence based medicine, the MedDiet represents the gold standard in preventive medicine, probably because of the harmonic combination of many elements with antioxidant and anti-inflammatory properties, which overwhelm any single nutrient or food item. The whole seems more important than the sum of its parts. PMID- 27552477 TI - Suppression of prairie grasses due to excess magnesium in a portion of a restored prairie. AB - In June 2002, the Department of Energy (DOE) began establishing the 60 ha Howell Prairie at the DOE Weldon Spring Site (WSS). In one area, the clay base is different from the other soil (subarea 2C). Vegetation sampling was conducted on four permanent plots across the prairie beginning in 2008, and shows that three of the four plots have strong establishment of native prairie species including prairie grasses. The fourth plot (subarea 2C), where the soil is different, shows significantly less native grass cover and stunted vegetation compared to the other three plots. One hundred twenty-five soil samples were taken in 6 different months and in 6 different years across the entire prairie restoration. Across the prairie, potassium (K) and phosphorus (P) were not limiting. The pH, organic matter content (OM), and cation exchange capacity (CEC) did not show trends related to the vegetation issues in subarea 2C. Ordination of the ratio of magnesium (Mg):K shows that Mg is very high in subarea 2C, which has been demonstrated to suppress the growth of prairie grasses. Subarea 2C contains interstratified kaolinite-smectite clay which contributes Mg to soil. It is hypothesized that an inexpensive, nondestructive treatment (addition of K) could be applied to remediate this area. PMID- 27552478 TI - Sudden Vision Loss and Mortality: The Jackson Heart Study. AB - PURPOSE: It is unknown whether sudden vision loss (SVL) is an independent marker for future cardiovascular disease (CVD) events in African Americans. We examined the hazard of future stroke or myocardial infarction (MI) and mortality associated with self-reported SVL lasting 24 hours or longer in a cohort of African Americans enrolled in the Jackson Heart Study (JHS). METHODS: The study sample comprised 4670 African Americans aged 20-95 years enrolled in the JHS without previous coronary heart disease or stroke at baseline. All participants who responded to the question "Have you ever had any sudden loss of vision or blurring, lasting 24 hours or longer?" on the baseline stroke questionnaire were included in the study. Ten years of follow-up data was used. Cox proportional hazards modeling was used to examine the association between SVL (n = 142) and risk of future stroke/MI and mortality. RESULTS: In age- and sex-adjusted Cox models, SVL was significantly associated with higher hazards of future stroke/MI (hazard ratio, HR, 2.08, 95% confidence interval, CI, 1.09-3.96) and mortality (HR 1.73, 95% CI 1.07-2.78). After adjusting for diabetes mellitus, total/high density lipoprotein cholesterol ratio, smoking, hypertension and income, the relationships between SVL and future stroke/MI (adjusted HR 1.51, 95% CI 0.78 2.90) or mortality (adjusted HR 1.29, 95% CI 0.78-2.11) were no longer significant. CONCLUSIONS: Self-reported SVL lasting 24 hours or longer was significantly associated with future stroke/MI and mortality, but its effect is likely a surrogate for underlying CVD risk factors rather than being an independent predictor. PMID- 27552479 TI - Self-Assembled PAEEP-PLLA Micelles with Varied Hydrophilic Block Lengths for Tumor Cell Targeting. AB - The properties of hydrophilic shell in micelles significantly affect the interaction between micelles and cells. Compared with frequently used polyethylene glycol (PEG) as the hydrophilic block, polyphosphoesters (PPEs) are superior in functionality, biocompatibility, and degradability. A series of amphiphilic poly(aminoethyl ethylene phosphate)/poly(l-lactide acid) (PAEEP-PLLA) copolymers were synthesized with hydrophilic PAEEP with different chain lengths. The corresponding self-assembled micelles were used for doxorubicin (Dox) entrapment. The length of hydrophilic PAEEP block on the shell affected the structure of micelles. PAEEPm-PLLA168 (m = 130 or 37) polymers formed vesicles, while PAEEPm-PLLA168 (m = 15 or 9) formed large compound micelles (LCMs), suggesting a difference in tumor cell uptake and intracellular trafficking. PAEEP15-PLLA168 polymer showed superiority on cellular uptake amount, intracellular drug release, and cell apoptosis. Lipid rafts and macropinocytosis are the leading endocytic pathways of PAEEP-PLLA micelles. The shape coupling between micelles and cell membrane facilitated cell surface features such as flattened protrusions (membrane protein) and inward-pointing hollows as well as efficient endocytosis. These results suggested that PAEEP-PLLA self-assembled block copolymer micelles may be an excellent drug delivery system for tumor treatment and that the hydrophilic chain length could regulate drug targeting to tumor cells. PMID- 27552480 TI - Inhibiting tumor necrosis factor-alpha before amyloidosis prevents synaptic deficits in an Alzheimer's disease model. AB - Deficits in synaptic structure and function are likely to underlie cognitive impairments in Alzheimer's disease. While synaptic deficits are commonly found in animal models of amyloidosis, it is unclear how amyloid pathology may impair synaptic functions. In some amyloid mouse models of Alzheimer's disease, however, synaptic deficits are preceded by hyperexcitability of glutamate synapses. In the amyloid transgenic mouse model TgCRND8, we therefore investigated whether early enhancement of glutamatergic transmission was responsible for development of later synaptic deficits. Hippocampi from 1-month-old TgCRND8 mice revealed increased basal transmission and plasticity of glutamate synapses that was related to increased levels of tumor necrosis factor alpha (TNFalpha). Treating these 1-month-old mice for 4 weeks with the TNFalpha inhibitor XPro1595 prevented synaptic deficits otherwise apparent at the age of 6 months. In this mouse model at least, reversing the hyperexcitability of glutamate synapses via TNFalpha blockade before the onset of amyloid plaque formation prevented later synaptic deficits. PMID- 27552481 TI - Organ-specific alteration in caspase expression and STK3 proteolysis during the aging process. AB - Caspases and their substrates are key mediators of apoptosis and strongly implicated in various physiological processes. As the serine/threonine kinase family is involved in apoptosis and serine/threonine kinase 3 (STK3) is a recently identified caspase-6 substrate, we assessed the expression and cleavage of STK3 in murine peripheral organs and brain regions during the aging process. We also assessed caspase-3, -6, -7, and -8 expression and activity in order to delineate potential mechanism(s) underlying the generation of the STK3 fragments observed and their relation to the apoptotic pathway. We demonstrate for the first time the cleavage of STK3 by caspase-7 and show that STK3 protein levels globally increase throughout the organism with age. In contrast, caspase-3, -6, 7, and -8 expression and activity vary significantly among the different organs analyzed suggesting differential effects of aging on the apoptotic mechanism and/or nonapoptotic functions of caspases throughout the organism. These results further our understanding of the role of caspases and their substrates in the normal aging process and highlight a potential role for STK3 in neurodegeneration. PMID- 27552482 TI - Investigation of synthetic aperture methods in ultrasound surface imaging using elementary surface types. AB - Synthetic aperture imaging methods have been employed widely in recent research in non-destructive testing (NDT), but uptake has been more limited in medical ultrasound imaging. Typically offering superior focussing power over more traditional phased array methods, these techniques have been employed in NDT applications to locate and characterise small defects within large samples, but have rarely been used to image surfaces. A desire to ultimately employ ultrasonic surface imaging for bone surface geometry measurement prior to surgical intervention motivates this research, and results are presented for initial laboratory trials of a surface reconstruction technique based on global thresholding of ultrasonic 3D point cloud data. In this study, representative geometry artefacts were imaged in the laboratory using two synthetic aperture techniques; the Total Focusing Method (TFM) and the Synthetic Aperture Focusing Technique (SAFT) employing full and narrow synthetic apertures, respectively. Three high precision metallic samples of known geometries (cuboid, sphere and cylinder) which featured a range of elementary surface primitives were imaged using a 5MHz, 128 element 1D phased array employing both SAFT and TFM approaches. The array was manipulated around the samples using a precision robotic positioning system, allowing for repeatable ultrasound derived 3D surface point clouds to be created. A global thresholding technique was then developed that allowed the extraction of the surface profiles, and these were compared with the known geometry samples to provide a quantitative measure of error of 3D surface reconstruction. The mean errors achieved with optimised SAFT imaging for the cuboidal, spherical and cylindrical samples were 1.3mm, 2.9mm and 2.0mm respectively, while those for TFM imaging were 3.7mm, 3.0mm and 3.1mm, respectively. These results were contrary to expectations given the higher information content associated with the TFM images. However, it was established that the reduced error associated with the SAFT technique was associated with significant reductions in side lobe levels of approximately 24dB in comparison to TFM imaging, although this came at the expense of reduced resolution and coverage. PMID- 27552483 TI - Prevalence and impact of irritable bowel syndrome in people with epilepsy. AB - PURPOSE: Epilepsy is known to be associated with affective disorders and sleep alterations, as well as with gastrointestinal conditions such as peptic ulcers and inflammatory bowel disease. There is comparatively little evidence linking epilepsy and gastrointestinal functional disorders. The objective of this study was to determine the prevalence and impact of irritable bowel syndrome (IBS) in patients with epilepsy. METHODS: We carried out a cross-sectional observational study on 65 consecutive people with epilepsy (PWE) and age- and sex-matched controls. Irritable bowel syndrome and functional dyspepsia (FD) diagnosis were based on Rome III criteria. Clinical and demographic characteristics were recorded, and instruments evaluating sleep quality, depressive/anxiety symptoms, insomnia, and health-related quality of life were also completed. RESULTS: Irritable bowel syndrome prevalence was significantly different between groups (3% in controls and 16% in patients with epilepsy; p=0.04), while no difference was found in FD (2% vs. 6%, respectively). People with epilepsy with IBS had significantly more insomnia and depressive and anxiety symptoms. No demographic or clinical characteristics were significantly different between groups. The presence of IBS did not affect health-related quality of life in PWE. On multivariate analysis, insomnia and depressive and anxiety symptoms did not independently predict IBS diagnosis. CONCLUSION: Irritable bowel syndrome was more frequent in PWE compared with that in healthy controls. Irritable bowel syndrome does not appear to affect health-related quality of life but is associated with a greater burden of affective symptoms and insomnia. PMID- 27552484 TI - The psychosocial impact of epilepsy on marriage: A narrative review. AB - There have been many studies exploring quality of life as well as the impact of epilepsy on the affected individual. However, epilepsy affects more than the patients themselves, and there seems to be a paucity of data regarding the impact of epilepsy beyond the person with epilepsy (PWE). In particular, it is uncertain what the impact of epilepsy on marriage may be. We therefore performed a narrative review to evaluate work measuring the psychosocial effect of epilepsy on marriage. We reviewed the literature on epilepsy and marriage by searching PubMed (Medline) and EMBASE and thoroughly examining relevant bibliographies. Forty-two papers were identified that addressed the issue of the psychosocial effect of epilepsy on marriage. The different approaches used to assess the impact of epilepsy on marriage can be broadly grouped into three categories: assessment of the social effect of living with epilepsy, which includes the marital prospects of PWEs and how changes in martial status associate with seizure frequency; assessment of quality of life (QOL) of PWEs; assessment of the association of social support with the disease burden of epilepsy. Within each of these approaches, different research methods have been employed including questionnaires, qualitative methods, and scales. The studies reviewed indicate that epilepsy has a severe impact on individuals and their families. While many quality-of-life surveys do comment on the marital status of the patient, there is little expansion beyond this. The impact that seizures may have on the partner of a patient with epilepsy is barely addressed. With increasing incidence of epilepsy in older populations, potential changes in the dynamic of a long-term marriage with the development of epilepsy in older age are not known. Similarly, the impact of marriage on concordance with medication or proceeding to, for example, surgical treatment for pharmacoresistant epilepsy has not been studied in detail. We suggest ways in which to address these aspects in order to better deliver holistic care to patients with epilepsy and their partners. PMID- 27552485 TI - Kinetic modeling of Candida shehatae ATCC 22984 on xylose and glucose for ethanol production. AB - Candida shehatae ATCC 22984, a xylose-fermenting yeast, showed an ability to produce ethanol in both glucose and xylose medium. Maximum ethanol produced by the yeast was 48.8 g/L in xylose and 52.6 g/L in glucose medium with ethanol yields that varied between 0.3 and 0.4 g/g depended on initial sugar concentrations. Xylitol was a coproduct of ethanol production using xylose as substrate, and glycerol was detected in both glucose and xylose media. Kinetic model equations indicated that growth, substrate consumption, and product formation of C. shehatae were governed by substrate limitation and inhibition by ethanol. The model suggested that cell growth was totally inhibited at 40 g/L of ethanol and ethanol production capacity of the yeast was 52 g/L, which were in good agreement with experimental results. The developed model could be used to explain C. shehatae fermentation in glucose and xylose media from 20 to 170 g/L sugar concentrations. PMID- 27552486 TI - Effectiveness of the Consecutive Alternating Administration Course of a Triple Antiviral Combination in Coxsackievirus B3 Infections in Mice. AB - Anti-enteroviral chemotherapeutics for clinical use are not registered so far, mainly due to the rapid development of drug-resistance. One of the possible approaches to overcome this problem is the use of combined chemotherapy. However, its application consisting of simultaneously given drugs, is not efficacious because of the development of multiple resistance. Here we present a novel approach for combined application of anti-enteroviral compounds, consisting of a consecutive alternating administration (CAA) course. CAA was tested on 2 in vivo models of Coxsackievirus B3 infection in newborn mice at inoculation dose of 20 MLD50 (50% mouse lethal dose): neurotropic (Nancy strain) and cardiotropic (Woodruff strain) infections. Compounds partnering in a triple combination were selected as enterovirus (EV) replication inhibitors with different mode of action - disoxaril (a VP1 blocker), guanidine.HCl (targeting 2C protein) and oxoglaucine (attacking 3A coding region). The application of this combination by CAA course resulted in around 40 and 60% survival rate in mice infected with Nancy and Woodruff virus, respectively, accompanied by a marked lengthening of the mean survival time (MST). The results obtained are proofs for the prospect of the treatment course by a triple combination through the CAA scheme as an approach interfering the occurrence of drug resistance at EV infections. PMID- 27552487 TI - The development of novel polypharmacological agents targeting the multiple binding sites of nicotinic acetylcholine receptors. AB - INTRODUCTION: Polypharmacology, which refers to the ability of a molecule to simultaneously interact with multiple target proteins, is shifting the drug discovery process from a 'one-drug-one-target' paradigm to a conceptual framework in which the multitarget profile of small molecules is proactively pursued. Nicotinic acetylcholine receptors (nAChRs) appear as attractive targets for the design of polypharmacological agents. These proteins participate in the regulation of multiple physiological processes and impressive progress has been made regarding their structure and function. Moreover, they contain several ligand binding sites, and a number of compounds including orthosteric and allosteric ligands, have been described. AREAS COVERED: The authors provide an overview of some of these topics and briefly discuss the mechanisms of action of some known promiscuous drugs that act at nAChRs, with the idea that this analysis will serve to guide the development of novel polypharmacological agents with a wide spectrum of actions. EXPERT OPINION: The authors anticipate that many innovative drugs will be compounds intentionally designed to have polypharmacological properties. Furthermore, the authors suggest that although the search for multitarget drugs acting at the orthosteric site of nAChRs will remain an interesting option, allosteric sites of these receptors exhibit a much greater polypharmacological potential. PMID- 27552488 TI - Toll like receptor mediated immune stimulation can be visualized in vivo by [18F]FDG-PET. AB - INTRODUCTION: High uptake of [18F]-2-fluorodeoxyglucose ([18F]FDG) by inflammatory cells is a frequent cause of false positive results in [18F]FDG positron-emission tomography (PET) for cancer diagnostics. Similar to cancer cells, immune cells undergo significant increases in glucose utilization following activation, e.g., in infectious diseases or after vaccination during cancer therapy. The aim of this study was to quantify certain immune effects in vitro and in vivo by [18F]FDG-PET after stimulation with TLR ligands and specific antibodies. METHODS: In vivo [18F]FDG-PET/magnetic resonance imaging (MRI) and biodistribution was performed with C57BL/6 mice immunized with CpG or LPS. Cellular [18F]FDG-uptake assays were performed with B cells and T cells or with whole spleen cells after stimulation with CpG, LPS and anti-CD3/CD28. In vitro and in vivo activation of B and T cells was examined by concomitant FACS analysis to correlate immune cell activation with the strength of [18F]FDG accumulation. RESULTS: We could show that TLR mediated activation of B cells increases [18F]FDG uptake, and that B cells show faster kinetics and greater effect than T cells stimulated by the CD3/CD28 pathway. In the whole spleen cell population the [18F]FDG signal was triggered mainly by the activation of B cells, corresponding closely to expression of typical stimulation markers. This finding could also been seen in vivo in [18F]FDG-PET/MRI, where the spleen was clearly visible after TLR stimulation and B cells showed upregulation of CD80 and CD86. CONCLUSION: In vivo TLR stimulation can be visualized by increased [18F]FDG uptake in lymphoid organs. The signal generated in the spleen after immunization might be mainly attributed to the activation of B cells within. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Knowledge of the composition of cells that take up [18F]FDG during vaccination or in response to therapy may improve successful treatment of cancer patients in the future. PMID- 27552489 TI - The effect of dance therapy on the balance of women over 60 years of age: The influence of dance therapy for the elderly. AB - Dance therapy is a physical activity that can lead to balance improvement in older adults. The aim of the study was to evaluate the effects of dance therapy on balance and risk of falls in older women. Twenty-four older women (mean age 66.4 years old) attended dance sessions for three months. Pretest/posttests were completed using the Postural Stability Test, the Limits of Stability Test, and the Fall Risk Test M-CTSIB. Results showed the Limits of Stability Test was significantly higher (17.5%) after dance classes. Regular use of dance therapy shows promise in improving balance by increasing the limits of stability. PMID- 27552491 TI - Exploring Post-Treatment Reversion of Antimicrobial Resistance in Enteric Bacteria of Food Animals as a Resistance Mitigation Strategy. AB - Antimicrobial drug use in food animals is associated with an elevation in relative abundance of bacteria resistant to the drug among the animal enteric bacteria. Some of these bacteria are potential foodborne pathogens. Evidence suggests that at least in the enteric nontype-specific Escherichia coli, after treatment the resistance abundance reverts to the background pre-treatment levels, without further interventions. We hypothesize that it is possible to define the distribution of the time period after treatment within which resistance to the administered drug, and possibly other drugs in case of coselection, in fecal bacteria of the treated animals returns to the background pre-treatment levels. Furthermore, it is possible that a novel resistance mitigation strategy for microbiological food safety could be developed based on this resistance reversion phenomenon. The strategy would be conceptually similar to existing antimicrobial drug withdrawal periods, which is a well-established and accepted mitigation strategy for avoiding violative drug residues in the edible products from the treated animals. For developing resistance-relevant withdrawals, a mathematical framework can be used to join the necessary pharmacological, microbiological, and animal production components to project the distributions of the post-treatment resistance reversion periods in the production animal populations for major antimicrobial drug classes in use. The framework can also help guide design of empirical studies into the resistance relevant withdrawal periods and development of mitigation approaches to reduce the treatment-associated elevation of resistance in animal enteric bacteria. We outline this framework, schematically and through exemplar equations, and how its components could be formulated. PMID- 27552492 TI - Penicillium spp.: prolific producer for harnessing cytotoxic secondary metabolites. AB - Secondary metabolites from fungal endophytes have become an interesting, attractive, and alternative source for novel pharmaceuticals. Several novel compounds with diversified chemical structures have been isolated from endophytic fungi. The genus Penicillium has been exploited worldwide for its biosynthetic potential for producing highly versatile cytotoxic secondary metabolites. Many of the compounds isolated from various species of the genus Penicillium have shown promising in-vitro as well as in-vivo growth-inhibitory properties against different human cancers. Thus, in relation to this genus, Penicillium represents the most dependable source of cytotoxic compounds with potential applications as leads for anticancer drugs. This review outlines endophytic secondary metabolites from the genus Penicillium with a relevant role as cytotoxic agents. PMID- 27552490 TI - Anti-N-Methyl-d-Aspartate Receptor Encephalitis in Adult Patients Requiring Intensive Care. AB - RATIONALE: Encephalitis caused by anti-N-methyl-d-aspartate receptor (NMDAR) antibodies is the leading cause of immune-mediated encephalitis. There are limited data on intensive care unit (ICU) management of these patients. OBJECTIVES: To identify prognostic factors of good neurologic outcome in patients admitted to an ICU with anti-NMDAR encephalitis. METHODS: This was an observational multicenter study of all consecutive adult patients diagnosed with anti-NMDAR encephalitis at the French National Reference Centre, admitted to an ICU between 2008 and 2014. The primary outcome was a good neurologic outcome at 6 months after ICU admission, defined by a modified Rankin Scale score of 0-2. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients were included from 52 ICUs. First-line immunotherapy consisted of steroids (n = 61/74; 82%), intravenous immunoglobulins (n = 71/74; 96%), and plasmapheresis (n = 17/74; 23%). Forty-five (61%) patients received second-line immunotherapy (cyclophosphamide, rituximab, or both). At 6 months, 57% of patients had a good neurologic outcome. Independent factors of good neurologic outcome were early (<=8 d after ICU admission) immunotherapy (odds ratio, 16.16; 95% confidence interval, 3.32-78.64; for combined first-line immunotherapy with steroids and intravenous immunoglobulins vs. late immunotherapy), and a low white blood cell count on the first cerebrospinal examination (odds ratio, 9.83 for <5 vs. >50 cells/mm3; 95% confidence interval, 1.07-90.65). Presence of nonneurologic organ failures at ICU admission and occurrence of status epilepticus during ICU stay were not associated with neurologic outcome. CONCLUSIONS: The prognosis of adult patients with anti-NMDAR encephalitis requiring intensive care is good, especially when immunotherapy is initiated early, advocating for prompt diagnosis and early aggressive treatment. PMID- 27552493 TI - Treatment patterns, complications, and direct medical costs associated with ankylosing spondylitis in Chinese urban patients: a retrospective claims dataset analysis. AB - AIM: To describe treatment pattern, complications, and direct medical costs associated with ankylosing spondylitis (AS) in Chinese urban patients. METHODS: The 2013 China Health Insurance Research Association (CHIRA) urban insurance claims database was used to identify patients with AS. The identified patients were stratified by AS treatments for the comparisons of well established AS related complications and direct medical costs. Conventional regression analyses adjusted the collected patient baseline characteristics to confirm the impact of treatments on complications and direct medical costs. RESULTS: Of the identified 1299 patients with AS, 18.0% received non-steroidal anti-inflammatory drugs (NSAID), 11.2% received immunosuppressant, 48.2% received NSAID plus immunosuppressant, 4.6% received biologic agents, and 17.9% received medications without indication for AS. Biologic group was associated with the lowest proportion of AS-related complications (8.3%) that was confirmed by multiple logistic regression analysis (odds ratio = 0.200, p = .017). The biologic group was also associated with highest direct medical costs (median: RMB = 14,539) that were confirmed by the multiple generalized linear model (coefficient = 1.644, p < .001). CONCLUSIONS: Biologics were not commonly used for AS in Chinese patients likely due to their high cost. Future studies are needed to confirm the potential long-term clinical benefits associated biologic treatment for AS. PMID- 27552494 TI - About the Existence of Organic Oxonium Ions as Mechanistic Intermediates in Water Solution. PMID- 27552495 TI - Stress and selective attention: Immediate and delayed stress effects on inhibition of return. AB - The relationship between attention and stress is far from understood. In fact, some studies reported better attentional selection during and after stress, some studies reported worse attentional selection, and some studies reported no effects of stress on attentional selection at all. We argue that given the complexity of both concepts more data are needed as to ultimately understand this relationship. Here we use an established attentional task that yields the inhibition of return (IOR) effect which is assumed to tap attentional control of oculomotor behavior. Participants were stressed with a Cold Pressor Test (CPT) and immediate and delayed effects of stress on hypothalamus-pituitary-adrenal (HPA) axis activation and IOR were analyzed. IOR was neither by immediate nor by delayed after-effects of the CPT stress procedure modulated, instead, we observed reliable and significant IOR in all experimental conditions. Attentional control of oculomotor behavior is therefore not altered after CPT stress, nor related to the post-stress activity of the HPA axis. PMID- 27552497 TI - Comparison of Surgical Outcome After Ahmed Valve Implantation for Patients With and Without Fluocinolone Intravitreal Implant (Retisert). AB - PURPOSE: To determine whether long-term, slow-release exposure to corticosteroids with Retisert promotes better surgical outcomes after Ahmed valve implantation. PATIENTS: This comparative retrospective cohort study included 17 study eyes (10 patients) with uncontrolled uveitis requiring Retisert and Ahmed implantation, and 55 control eyes (51 patients) with other types of medically uncontrolled glaucoma that only received Ahmed. MATERIALS AND METHODS: Main outcome measures were intraocular pressure (IOP), glaucoma eye drops per day, best-corrected visual acuity, early complications, and late complications at 1, 3, 6, and 12 months. Linear mixed effects models were used to model IOP, glaucoma drops per day, and visual acuity at 1 year after surgery. RESULTS: At 1 year, the study eyes had a mean IOP of 12.24, which was lower than that for control eyes at 15.17 (P=0.04). At 1 year, the average number of glaucoma eye drops used per day for study eyes was 1.4, which was lower than that for control eyes at 2.3 (P=0.03). At 1 year, there were no statistically significant differences in change in visual acuity, early complications, and late complications between study and control eyes. CONCLUSIONS: Patients who received a Retisert implantation had lower IOP and used fewer glaucoma eye drops compared with control eyes at 1-year post-Ahmed valve surgery. This study suggests that long-term, slow-release corticosteroid medication from Retisert (fluocinolone acetonide) may improve the surgical outcome for patients with an Ahmed valve implantation and/or Retisert helps control uveitis in patients with uveitic glaucoma receiving Ahmed valves. PMID- 27552498 TI - The Fluctuation of Intraocular Pressure Measured by a Contact Lens Sensor in Normal-Tension Glaucoma Patients and Nonglaucoma Subjects. AB - PURPOSE: We compared the fluctuation of intraocular pressure (IOP) in normal tension glaucoma (NTG) patients and individuals with nonglaucoma eyes. We obtained continuous IOP values using a SENSIMED Triggerfish contact lens sensor. MATERIALS AND METHODS: The eyes of 12 nonglaucoma subjects and 14 NTG patients were examined. In all 26 subjects, the IOP fluctuation was measured continuously for 24 hours with a contact lens sensor. We evaluated the range of IOP fluctuations over the 24-hour period separately for diurnal IOP and nocturnal IOP and identified each subject's maximum value. The range of IOP fluctuation were analyzed, cutoff level of IOP fluctuation was calculated using receiver operating characteristic curve analyses. RESULTS: The mean IOP in the NTG eyes was 11.5+/ 2.4 mm Hg and that in the nonglaucoma eyes was 12.7+/-2.0 mm Hg, a nonsignificantly difference (P=0.175). The 24-hour range of IOP fluctuations in the NTG group was significantly larger than that of the nonglaucoma group (P=0.007). The percentage of NTG patients who had the peak time of IOP fluctuation during nocturnal sleep was 57.1%, whereas the corresponding rate for the nonglaucoma eyes was 91.7%. The cutoff level of IOP fluctuation for glaucoma was 442 mVeq (sensitivity=1.00; specificity=0.571). CONCLUSIONS: The range of IOP fluctuation was larger in the eyes with NTG than in the nonglaucoma eyes. This larger fluctuation might be one of the reasons underlying the aggravation of the visual field by NTG. Measurements of 24-hour continuous IOP might be one of the useful methods to distinguish NTG from nonglaucoma eyes. PMID- 27552499 TI - Acute Primary Angle Closure in the Fellow Eye as a Complication of Facedown Position After Vitrectomy Surgery. AB - PURPOSE: To report a case of acute primary angle closure that developed in the fellow eye rapidly after facedown position after vitrectomy surgery. PATIENTS AND METHODS: A 66-year-old female developed acute primary angle closure in the fellow eye approximately 1.5 hours after facedown position after vitrectomy surgery for macular hole. RESULTS: The intraocular pressure was controlled after treatment that included halting the facedown position, intravenous mannitol injection, and topical pilocarpine instillation. Facedown position was continued after laser peripheral iridotomy was performed. The intraocular pressure was controlled within normal range even after pilocarpine was withdrawn. CONCLUSIONS: Although rare, the potential risk of acute-angle closure should be explicitly explained to patients being considered for facedown position after vitrectomy. Prophylactic intervention, such as laser peripheral iridotomy, could be considered for anatomically predisposed eyes. PMID- 27552500 TI - Randomized Prospective Study of the Use of Anti-Inflammatory Drops After Selective Laser Trabeculoplasty. AB - PURPOSE: Evaluating the use of Indomethacin, Dexamethasone, and no anti inflammatory treatment immediately after selective laser trabeculoplasty (SLT). MATERIALS AND METHODS: Prospective randomized clinical trial of 132 eyes. Both eyes of the patient underwent SLT. One of the eyes was treated with Indomethacin 0.1% or Dexamethasone 0.1% 3 times daily for 1 week; the other eye did not receive any anti-inflammatory treatment. Intraocular pressure (IOP) and inflammatory parameters were recorded at 1 hour, 1 week, 1, 3, and 6 months. RESULTS: Cells in the anterior chamber were present in 57% to 71% of the patients after 1 hour. About 16% to 37% of the patients reported pain/discomfort after 1 hour. Redness was present before SLT in 29% to 34% of the patients, probably due to antiglaucoma medication. After 1 hour, the amount of redness recorded raised to 32% to 42%, but the amount of patients with redness returned to pretreatment levels after 1 week. An IOP peak of >5 mm Hg above baseline IOP 1 hour after laser was present in 3% to 9% of the patients. IOP lowered 11% to 21% compared with IOP at baseline. The number of medications needed changed from 1.45 to 1.49 before, to 0.23 to 0.45 six months after SLT.No differential effects based on the kind of anti-inflammatory treatment or no treatment were found for any of the parameters. CONCLUSIONS: SLT induces little inflammation: anti-inflammatory drops do not make a significant difference in pain, redness, cells in anterior chamber, or peak IOP following SLT.The IOP-lowering effect of the SLT is not influenced by the use of Indomethacin or Dexamethasone. PMID- 27552496 TI - Non-medical use of prescription opioids is associated with heroin initiation among US veterans: a prospective cohort study. AB - AIMS: To estimate the influence of non-medical use of prescription opioids (NMUPO) on heroin initiation among US veterans receiving medical care. DESIGN: Using a multivariable Cox regression model, we analyzed data from a prospective, multi-site, observational study of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans in care in the United States. Approximately annual behavioral assessments were conducted and contained self reported measures of NMUPO and heroin use. SETTING: Veterans Health Administration (VHA) infectious disease and primary care clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh and Washington, DC. PARTICIPANTS: A total of 3396 HIV-infected and uninfected patients enrolled into the Veterans Aging Cohort Study who reported no life-time NMUPO or heroin use, had no opioid use disorder diagnoses at baseline and who were followed between 2002 and 2012. MEASUREMENTS: The primary outcome measure was self-reported incident heroin use and the primary exposure of interest was new-onset NMUPO. Our final model was adjusted for socio-demographics, pain interference, prior diagnoses of post-traumatic stress disorder and/or depression and self-reported other substance use. FINDINGS: Using a multivariable Cox regression model, we found that non-medical use of prescription opioids NMUPO was associated positively and independently with heroin initiation [adjusted hazard ratio (AHR) = 5.43, 95% confidence interval (CI) = 4.01, 7.35]. CONCLUSIONS: New-onset non medical use of prescription opioids (NMUPO) is a strong risk factor for heroin initiation among HIV-infected and uninfected veterans in the United States who reported no previous history of NMUPO or illicit opioid use. PMID- 27552501 TI - Aqueous-Vortex Derivation: A Preliminary Study on Rabbits. AB - PURPOSE OF THE STUDY: The purpose of the study was to determine the feasibility of establishing a derivation between the anterior chamber (AC) and a vortex vein to lower the intraocular pressure (IOP). MATERIALS AND METHODS: A derivation between the AC and a vortex vein was performed in 1 eye of 16 albino rabbits, whereas the other eye was kept as the control. Derivations were performed using a Teflon tube with an external diameter of 0.90 mm and an inner diameter of 0.50 mm. IOP measurements, using a Goldmann tonometer, were conducted 2 or 3 times a week for periods of 30, 60, 90, 120, 150, and 180 days. RESULTS: A significant difference in the IOP between operated and nonoperated eyes was obtained. Reductions in the IOP varying from 40% to 50% were found in this study. The patency of all tubes was confirmed, no tube was slipped out of the venous lumen, and none of the tubes penetrated deeper into the AC. The tubes did not move backward and out of the AC. No keratic precipitates, synechiae, or lens changes were observed. Iris prolapse, wound leakage, infection, and hyphema were not encountered. Microscopically, no venous thrombosis was encountered in these series. CONCLUSIONS: The results, corroborated by the anatomopathology, proved the viability of the aqueous-vortex derivation for the treatment of the ocular hypertension and some types of glaucoma with damage of the trabecular meshwork. PMID- 27552502 TI - Results From a Modified Bleb Needling Procedure With Continuous Infusion Performed in the Operating Room. AB - PURPOSE: Needling of a scarred trabeculectomy bleb is often performed in the office using a slit-lamp microscope as an alternative to additional surgery to lower intraocular pressure (IOP). However, the success rate in an office setting is highly variable, with reported success rates as low as 13%. We report a retrospective assessment of an intraoperative needling technique for reviving failed blebs. DESIGN: A retrospective chart review. PARTICIPANTS: Patients undergoing the intraoperative modified bleb revision technique in the setting of a failed trabeculectomy due to scarring at the Wilmer Eye Institute, Johns Hopkins Hospital between August 16, 2010 and August 29, 2012. METHODS: Patients with uncontrolled IOP were operated on using a modified bleb needling technique. In this technique, a 25-G infusion cannula is placed in the anterior chamber and fibrotic adhesions within the bleb are lysed with a 25-G needle. The continuous infusion of balanced salt solution from the anterior chamber causes bleb elevation, which helps to guide the endpoint of lysis for the procedure. A subconjunctival injection of 5-fluorouracil is given at the conclusion of each case. MAIN OUTCOME MEASURES: IOP reduction and number of glaucoma medications at postoperative day 1, week 1, month 1, month 3, month 6, and month 12. RESULTS: A total of 33 eyes of 30 patients were included. At the visit before the procedure, the mean (+/-SD) IOP was 22.1+/-9.2 (range, 11 to 58) and subjects were using an average of 2.3+/-1.4 (range, 0 to 4) glaucoma medications. The mean IOP reduction was 8.7 mm Hg [95% confidence interval (CI), 5.6-11.8] at postoperative day 1, 8.1 mm Hg (95% CI, 4.0-12.3) at week 1, 8.9 mm Hg (95% CI, 5.3-12.5) at month 1, 8.1 mm Hg (95% CI, 4.2-12.0) at month 3, 8.2 mm Hg (95% CI, 3.9-12.5) at month 6, and 6.2 mm Hg (95% CI, 3.6-8.7) at month 12. IOP was reduced about 30% to 40% compared with baseline at each time point (P<0.05). The average reduction in medications used was 1.7 at day 1, 1.0 at month 1, 1.2 at month 3, 1.5 at month 6, and 0.5 at month 12. Seven patients underwent repeat needling. Overall, 64% of subjects maintained IOP at or below their target after 12 months. CONCLUSIONS: A modified bleb needling procedure performed in the operating room can successfully lower IOP in the setting of a previous trabeculectomy in over 60% of subjects a year after the procedure. PMID- 27552503 TI - Comparison of the Intraocular Pressure Variation Provoked by Postural Change and by the Water Drinking Test in Primary Open-angle Glaucoma and Normal Patients. AB - PURPOSE: To evaluate the intraocular pressure (IOP) peak and variability detected by moving the body from sitting to supine position (postural test) and by the water drinking test (WDT) in normal and primary open-angle glaucoma (POAG) subjects. PATIENTS AND METHODS: Prospective, cross-sectional observational analysis of 14 eyes of 14 normal subjects and 31 eyes of 31 patients with POAG. All POAG subjects were under clinical therapy. IOP measurements were all performed on the same day. RESULTS: When the subjects moved to the supine position, there was an IOP increase of 1.36+/-1.34 and 2.84+/-2.21 mm Hg in the normal and POAG groups, respectively (P=0.011). During the WDT, mean IOP peak and fluctuation in the POAG group was 19.29+/-4.10 and 4.13+/-2.33 mm Hg, respectively. These levels were significantly higher in comparison with the normal group (16.50+/-3.76 and 2.71+/-0.99 mm Hg; P=0.018 and 0.022, respectively). The mean peak IOP observed in the WDT was significantly higher than the IOP in the supine position (19.29+/-4.10 vs. 17.32+/-4.66 mm Hg, P=0.013). The mean IOP increase during the WDT was also significantly higher when compared with the postural test (4.13+/-2.33 vs. 2.84+/-2.21 mm Hg, P=0.019). CONCLUSIONS: POAG eyes demonstrated a significant IOP increase when assuming the supine position and during the WDT. The IOP increase during the WDT was significantly higher than the IOP increase after postural test. Hence, the results of both tests are not interchangeable. PMID- 27552504 TI - Trabeculotomy in the Treatment of Pediatric Uveitic Glaucoma. AB - PURPOSE: To evaluate the efficacy and safety of trabeculotomy in the treatment of pediatric uveitic glaucoma (UG). MATERIALS AND METHODS: We retrospectively reviewed all cases that underwent trabeculotomy for pediatric UG at our center between 2008 and 2014. Up to 2 trabeculotomies per eye were performed in patients with medically controlled uveitis. Surgical success was defined as final intraocular pressure <22 mm Hg and >=6 mm Hg after 1 or 2 trabeculotomies, with or without medications. Kaplan-Meier survival analyses were done. RESULTS: A total of 33 trabeculotomies were performed in 28 eyes of 22 patients. Diagnoses included UG associated with juvenile idiopathic arthritis (68.2%), idiopathic uveitis (22.7%), and pars planitis (9.1%). The average age at surgery was 9.8+/ 3.7 (5 to 17) years. With a mean follow-up of 33.6+/-18.3 (10 to 78) months, the overall surgical success was 81.8%. The cumulative survival probability after up to 2 trabeculotomies was 0.86 (95% confidence interval, 0.71-0.93) at 12 months and 0.77 (95% confidence interval, 0.60-0.87) at 24 months. Four (11.5%) eyes required a second trabeculotomy to achieve surgical success and 4 (7.7%) required filtrating procedures. Intraocular pressure improved from 31.4+/-7.6 (18 to 50) mm Hg preoperatively to 15.0+/-3.6 (8 to 23) mm Hg at final visits, whereas the number of glaucoma medications decreased from 4.2+/-1.1 (1 to 5) to 0.4+/-1.0 (0 to 4). Visual acuity and intraocular inflammation remained stable (P>0.05) and there were no major complications. CONCLUSIONS: Trabeculotomy is a safe and effective surgery for pediatric UG. PMID- 27552505 TI - Mathematical Discrepancies of the Tono-Pen Applanation Tonometer. AB - PURPOSE OF THE STUDY: The purpose of the study was to determine if Tono-Pen tonometers use simple average and coefficient of variation (CV) algorithms to calculate intraocular pressure (IOP). MATERIAL AND METHODS: IOPs were measured as part of routine ocular examination in 152 client-owned dogs. Using 11 Tono-Pen's, a total of 778 averaged readings were collected. Individual IOP readings, and average IOP and CV displayed by the instrument, were recorded. Average IOP and CV were then manually calculated from individual readings and compared with those displayed by the instrument. RESULTS: The mean absolute difference between the calculated and displayed average IOP was 1.37+/-2.01 mm Hg (P<0.001). In 6% of cases, the calculated average IOP was 5 to 15 mm Hg different from the displayed average IOP. The difference between the displayed and calculated average IOP was significantly higher in hypertensive eyes with displayed IOP>=25 mm Hg. Calculated CV was equal to, lower than, or greater than displayed CV in 28.6%, 1.5%, and 69.7% of cases, respectively. In 17.6% of cases, calculated CV was >20%, but displayed CV was <5%. Receiver operating characteristic analysis could not correlate number of individual IOP readings with magnitude of difference in average IOP. CONCLUSIONS: Calculated average IOP and CV differ significantly from values displayed by the instrument, especially at higher IOPs. A difference of >=5 mm Hg between calculated and displayed average IOP seen in 6% of cases may impact clinical judgement. Displayed CV<5% does not correlate with accurate IOP measurement based on individual results. PMID- 27552506 TI - Correlation in Severity Between Glaucoma and Erectile Dysfunction. AB - PURPOSE: To examine the association between open-angle glaucoma and erectile dysfunction (ED), and investigate the correlation in severity between these 2 conditions. METHODS: Cross-sectional study with patient questionnaire and retrospective chart review. A total of 167 male patients over 40 years of age who attended ophthalmology clinic visits in Vancouver, British Columbia, Canada, participated in the study by providing written consent and responding to the survey. Patients with previous radiation or surgical prostate treatment were excluded, leaving final sample sizes of 61 glaucoma patients and 67 control patients. Presence and severity of ED was determined using a validated patient questionnaire (the International Index of Erectile Function questionnaire). Presence of glaucoma was based on previous clinical diagnosis, and severity was graded based on visual field index using a 30-2 visual field test with the SITA Standard protocol. Bivariate analysis examined the presence of ED in glaucoma patients versus controls. Risk factors including dyslipidemia, diabetes, hypertension, and smoking were adjusted for using multiple logistic regression. The association between glaucoma and ED severity was assessed with correlation and scatterplot analysis. RESULTS: Glaucoma was found to be a significant risk factor for ED in our population, with an odds ratio of 2.58 (95% confidence interval, 1.15-5.83). Severity of glaucoma and ED were significantly correlated (r=0.365, P=0.007). CONCLUSIONS: Our results demonstrate that there is a positive association between the presence of ED and the diagnosis of glaucoma and a positive association between the severity of ED and the severity of glaucoma. PMID- 27552507 TI - Meta-Analysis of Association of Obstructive Sleep Apnea (OSA) With Glaucoma. PMID- 27552508 TI - Changes in the Choroidal Thickness and Axial Length Upon Mannitol Infusion in Patients With Asymmetric Intraocular Pressure. AB - BACKGROUND/AIMS: To evaluate the changes in the choroidal thickness (CT) and axial length (AL) upon systemic mannitol infusion in glaucoma patients with asymmetric intraocular pressure (IOP). MATERIALS AND METHODS: Forty glaucoma patients with asymmetric IOP, with the IOP of 1 eye >=40 mm Hg and the fellow eye <25 mm Hg, were administered 150 mL of a 20% mannitol infusion to reduce the IOP. The CT and AL were measured before and an hour after the infusion. The relationship between the IOP reduction and the changes in the CT and AL were investigated. RESULTS: The mean decrease in the IOP was -14.23 mm Hg (32.15%) and -4.13 mm Hg (21.40%) in the eyes with higher IOP and their fellow eyes, respectively. The mean changes in the subfoveal CT were 19.28 um (9.20%; P<0.001) and 2.60 um (1.93%; P=0.452) in the eyes with higher IOP and their fellow eyes, respectively. The mean changes in the AL were -0.10 um (0.42%; P<0.001) and -0.33 mm (0.14%; P=0.008) in the eyes with higher IOP and their fellow eyes, respectively. Stepwise analysis revealed that the percent IOP change is the most influential factor on the percent change of the subfoveal CT (P<0.0001; R=0.3). CONCLUSIONS: These results suggest that large IOP changes upon mannitol infusion cause the shortening of the AL in both the eyes and the thickening of the choroid only in the eyes with a higher IOP. PMID- 27552509 TI - Evaluation of a Trabecular Micro-Bypass Stent in Pseudophakic Patients With Open Angle Glaucoma. AB - PURPOSE OF THE STUDY: The purpose of the study was to evaluate the safety and efficacy of the iStent Trabecular Micro-Bypass stent in pseudophakic patients with open-angle glaucoma. METHODS: Retrospective, consecutive case series from October 2012 to May 2015 with no exclusion criteria. The series comprised 42 pseudophakic eyes with open-angle glaucoma that were implanted with 1 iStent. Data were collected preoperatively, and postoperative data were collected at 1 day, 1 week, 1, 3 and 6 months, 1 year, 18 months and 2 years. Data included intraocular pressure (IOP), number of glaucoma medications, the incidence of postoperative IOP pressure spikes >=15 mm Hg at any timepoint, and the need for additional surgery. RESULTS: The mean preoperative IOP was 20.26+/-6.00 mm Hg. At 1 year postoperatively, the mean IOP was 16.34+/-3.78 mm Hg (P<0.01). At 2 years postoperatively, the mean IOP was 13.62+/-4.55 (P<0.01). The mean number of glaucoma medications was 1.95+/-1.01 preoperative and 1.69+/-1.28 (P>0.05) at 1 year postoperatively. Postoperatively, 3 eyes (7%) experienced an IOP increase of 15 mm Hg above their baseline IOP that responded to topical therapy. In total, 96% of patients with an IOP>=19 mm Hg achieved a reduction in IOP at their last collected follow-up. CONCLUSIONS: The insertion of the iStent Trabecular Micro Bypass stent effectively lowers IOP in pseudophakic patients with open-angle glaucoma. Although medication use was not significantly reduced postoperatively at 1 year, 80% of patients either experienced a reduction or no change in medication use. The safety profile appears favorable with a low rate of IOP spikes and only 1 patient requiring additional surgery. PMID- 27552510 TI - Scanning Electron Microscopy Evaluation of an EX-PRESS Mini Glaucoma Shunt After Explantation. AB - We report a case of an explanted stainless steel miniature glaucoma drainage device (EX-PRESS) implanted under a scleral flap for pseudoexfoliation open-angle glaucoma surgical treatment. The glaucoma shunt was implanted in a 75-year-old white man with medically refractive glaucoma. Cataract surgery was performed simultaneously. After 2 years, the shunt extruded through the scleral flap and the conjunctiva and it was, therefore, explanted. Scanning electron microscopy images of the EX-PRESS mini glaucoma shunt were acquired to verify the patency of the device lumen and the presence of fibrosis or cellular adhesion on the device. Energy dispersive spectroscopy for chemical surface characterization of the EX PRESS shunt was performed. Scanning electron microscopy-acquired images showed minimal extracellular material proliferation on the lumen device. The energy dispersive spectroscopy analysis revealed a high peak of carbon suggesting the organic nature of the residuals found on the shunt lumen. The surface showed few superficial pits, likely due to an initial corrosion process. PMID- 27552511 TI - Selective Laser Trabeculoplasty Reduces Intraocular Pressure Peak in Response to the Water Drinking Test. AB - PURPOSE: To determine the effect of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) peak and fluctuation induced by the water drinking test (WDT) in patients with open-angle glaucoma and ocular hypertension. METHODS: Patients with open-angle glaucoma or ocular hypertension underwent the WDT before and after SLT within a 12-month period. No other changes to therapeutic regimen were permitted. IOP was measured with a Goldmann applanation tonometer at baseline and every 15 minutes for 45 minutes following a fluid challenge of 800 mL over 15 minutes. Baseline, peak, and percentage fluctuation in IOP from baseline were compared using a repeated measures analysis of variance with Bonferroni adjustment. RESULTS: Twenty eyes from 20 patients were included in this study. The median patient age was 73+/-15 years (interquartile range) and 70% of patients were female. Ten eyes (50%) had a diagnosis of primary open-angle glaucoma and 10 eyes had ocular hypertension. Following SLT there was a statistically significant reduction in mean baseline IOP from 16.9+/-2.4 to 14.2+/-2.3 mm Hg (P<0.001), peak IOP from 21.9+/-3.7 to 16.9+/-3.1 mm Hg (P<0.001). CONCLUSIONS: Patients with open-angle glaucoma and ocular hypertension treated with SLT have significantly reduced peak IOPs and fluctuation in IOP in response to the WDT. PMID- 27552512 TI - Ahmed Versus Baerveldt Glaucoma Drainage Implantation in Patients With Markedly Elevated Intraocular Pressure (>=30 mm Hg). AB - PURPOSE: Glaucoma patients with markedly elevated intraocular pressure (IOP) are at risk for developing severe hypotony-related complications. The goal of this study was to compare the surgical outcomes of the Ahmed Glaucoma Valve (AGV) and the Baerveldt Glaucoma Implant (BGI) in this patient population. METHODS: Patients with preoperative IOP>=30 mm Hg were included. Outcome measures were: (1) surgical failure (IOP>21 mm Hg or <30% reduction from baseline or IOP<=5 mm Hg on 2 consecutive follow-up visits after 3 mo, or additional glaucoma surgery, or loss of light perception) and (2) surgical complications. RESULTS: A total of 75 patients were included: 37 in the AGV group and 38 in the BGI group. The mean+/-SD follow-up was 2.3+/-1.6 years for the AGV group and 2.4+/-1.7 years for the BGI group (P=0.643). Mean preoperative IOP was 38.7+/-6.5 mm Hg for the AGV group and 40.8+/-7.6 mm Hg for the BGI group. At the last follow-up, 10 (27.0%) patients failed in the AGV group compared with 6 (15.8%) patients in the BGI group (P=0.379). The BGI group had higher rate of flat or shallow anterior chamber (n=4, 10%) compared with the AGV group (n=0, 0%) (P=0.043). CONCLUSIONS: Failure rates of AGV and BGI in patients with IOP>=30 mm Hg were comparable. There were more early hypotony-related complications in the BGI group; however, none were vision threatening. Both glaucoma drainage implants were effective in treating patients with uncontrolled glaucoma in an emergency setting. PMID- 27552514 TI - Comment on the Paper by Mondzelewski and Colleagues: "Intraocular Pressure During Robotic-assisted Laparoscopic Procedures Utilizing Steep Trendelenburg Positioning." J Glaucoma. 2015;24(6):399-404. PMID- 27552513 TI - The Wills Eye Glaucoma App: Interest of Patients and Their Caregivers in a Smartphone-based and Tablet-based Glaucoma Application. AB - PURPOSE: To evaluate the interest of glaucoma patients and their caregivers in a smartphone-based and tablet-based glaucoma application (App), developed by the Wills Eye Glaucoma Research Center in collaboration with Drexel University. MATERIALS AND METHODS: Cross-sectional survey of patients with glaucoma and their caregivers. Main outcome measures are answers to survey questions regarding how receptive participants are to using the Glaucoma App. RESULTS: Fifty subjects completed the survey. The mean age (SD) was 59.5 (+/-17.3) years. A total of 88.6% of the participants lived in a household with access to a smartphone or tablet. The majority (72.3%) of participants would consider downloading the Glaucoma App, and younger participants (<65 y) were more likely to do so compared with their older (>=65 y) counterparts, P=0.025. Participants were more likely to download the App if it was free of charge, compared with a version that costs $3, P=0.018. Although only about one third (37.8%) of participants used eye drop reminders, nearly 3 of 4 (72.9%) participants were receptive to using the automated reminder feature of the Glaucoma App. CONCLUSIONS: Glaucoma patients and their caregivers were very interested in using a Glaucoma App; however, many were not willing to spend $3 for an App they seem to value. The free Wills Eye Glaucoma App currently available on the Apple store, includes educational videos, eye drop and appointment reminders, medical and ocular data storage, visual field tutorial, and intraocular pressure tracker. These features aim to increase patients' level of knowledge about glaucoma and improve their adherence to medication and follow-up appointment recommendations. PMID- 27552515 TI - Supra-Tenon Capsule Implantation of the Ahmed Glaucoma Valve in Refractory Pediatric Glaucoma. AB - PURPOSE: To evaluate the efficacy of supra-Tenon capsule implantation of an Ahmed glaucoma valve (AGV) as a measure to decrease the fibrotic potential of the Tenon capsule on bleb formation and its subsequent effect on intraocular pressure (IOP) control in children with refractory glaucoma. SETTING: Mansoura Ophthalmic Centre, Faculty of Medicine, Mansoura University, Egypt. DESIGN: A prospective interventional study. PATIENTS AND METHODS: Twenty-two eyes of 12 children with refractory glaucoma underwent supra-Tenon capsule implantation of AGV. Ophthalmic examinations under general anesthesia including measurement of the corneal diameter and the IOP with Perkin's tonometer were performed preoperatively, on the first postoperative day, the first postoperative week, weekly for the first month, 2-weekly for the following 3 months, and monthly for at least 18 months. Postoperative complications and the number of glaucoma medications used preoperatively and postoperatively were recorded. The paired Student t test was used to compare preoperative and postoperative data. RESULTS: There were 12 eyes (54.6%) with refractory congenital glaucoma, 7 eyes (31.8%) with refractory pseudophakic glaucoma, and 3 eyes (13.6%) with refractory aphakic glaucoma. Patients included 10 male (83.3%) and 2 female (16.7%) children with a mean age of 16.3+/-9.7 months. The mean follow-up duration was 24.1+/-4.3 months. There was a statistically significant difference between the mean preoperative IOP (30.7+/-2.88 mm Hg) and the mean postoperative IOP (16.1+/-3.60 mm Hg) (t=16.22 and P=0.000, with a mean decrease in the IOP by 47.6%). The difference between the mean number of antiglaucoma medications before surgery (1.86+/-0.4) and after surgery (1.0+/-0.9) was also statistically significant (t=4.31 and P=0.000). Total success was achieved in 18 eyes (81.9%). Postoperative complications included tube exposure and slippage (10%), hypotony (10%), and hyphema (5%). CONCLUSIONS: Supra-Tenon capsule implantation of the AGV was successful in controlling the IOP with few postoperative complications in the management of children with refractory glaucoma. PMID- 27552516 TI - Squeeze Me if You Can: Variability in Force Requirements to Extract a Drop From Common Glaucoma Bottles. AB - PURPOSE: To determine the force requirements to dispense a single drop from commonly prescribed brand and generic topical glaucoma medications and correlate these findings with pinch strength in a representative patient population. PATIENTS AND METHODS: Four bottles of each medication were tested: 2 in the vertical and 2 in the horizontal orientation. Bottles were housed in a customized force gauge apparatus designed to mimic ballpoint fingertip contact with a bottle tip. For all bottles, each of the first 10 dispensed drops was tested and then tests were performed in increments of 10 until the bottle was empty. For each tested drop, the maximum force and displacement were electronically measured. Concurrently, maximum pinch strength was measured on consecutive glaucoma patients. RESULTS: A total of 84 bottles from 21 bottle designs were tested. There was significant variability across the designs, with roughly a 7-fold (0.67 to 4.49 kgf) and 4-fold (0.81 to 3.00 kgf) difference in force requirements in the vertical and horizontal positions, respectively. Of 53 enrolled patients in the glaucoma clinic, the mean pinch strength was 5.05 (range, 1.23 to 10.4 kgf) and 4.82 (range, 1.47 to 10.67 kgf) kgf for the right and left hands, respectively. CONCLUSIONS: There is statistically significant variability in the force required to squeeze a drop from common glaucoma medications, and a representative sampling of clinic patients suggests that many likely struggle with the force requirements of several bottle designs. These data further support standardization of topical glaucoma drug delivery and design. PMID- 27552517 TI - Efficacy of Topically Administered Rho-Kinase Inhibitor AR-12286 in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma. AB - PURPOSE: To evaluate the efficacy of rho-associated protein kinase inhibitor, AR 12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation. METHODS: Prospective, double-masked, randomized, interventional study. Patients with XFS and OHT or XFG were enrolled. The study eyes were treated once daily with AR 12286, randomized to 0.5% or 0.7% for 24 weeks. Visits included baseline, 1, 4, and 12 weeks after drug initiation; at 12 weeks AR-12286 was discontinued for 1 week and was resumed at week 13. At the week 24 visit, AR-12286 was discontinued, and a final reexamination was performed at week 25. RESULTS: Ten patients were treated. Mean baseline IOP was 25+/-2.4 mm Hg, mean IOP was reduced to 19.1+/-2.3 mm Hg at 1 week (P<0.001), 17.5+/-3.6 mm Hg at 4 weeks (P<0.001), and 17.4+/-3.6 mm Hg at 12 weeks (P<0.001), yielding an average IOP reduction of 23.6%, 30%, and 30.4%, respectively. At the week 13 visit, 1 week after the drug was discontinued, mean IOP increased to 21.6+/-5.4 mm Hg (P=0.06 compared with baseline visit). At week 24, the mean IOP was 21.8+/-7.8 mm Hg (P=0.2, and AR 12286 was discontinued). At week 25, the mean IOP was 21.3+/-5.3 mm Hg (P=0.06). CONCLUSIONS: AR-12286 was well tolerated and provided statistically significant reduction in IOP in patients with XFS and OHT or XFG. This drug may represent an additional therapeutic paradigm for the treatment of XFG. PMID- 27552518 TI - Patterns of Damage in Young Myopic Glaucomatous-appearing Patients With Different Optic Disc Tilt Direction. AB - PURPOSE OF THE STUDY: The purpose of the study was to compare patterns of damage in young myopic glaucomatous-appearing patients with horizontal disc tilt (HDT) to a control group of patients with vertical disc tilt (VDT). PATIENTS AND METHODS: We consecutively enrolled 104 eyes of 104 young, myopic, glaucomatous appearing patients without or with early visual field (VF) defects. The eyes were divided into those with HDT or VDT. The clinical characteristics of the peripapillary retinal nerve fiber layer (pRNFL) and VF damage were compared between groups after matching for age, refractive error, and neural rim area using spectral-domain optical coherence tomography and standard automated perimetry 24-2 VF testing. Multivariate logistic regression analysis was performed to determine the risk factors associated with more advanced VF damage (mean deviation <-6 dB) at initial presentation. RESULTS: The asymmetric loss of pRNFL thickness between hemispheres was significantly greater in the HDT group (P=0.002). Myopic eyes with HDT were more likely to have peripheral VF loss than those with VDT (P<0.05). HDT was an independent risk factor for more advanced VF loss at initial presentation (P=0.011). CONCLUSIONS: The disc tilt direction may be related to asymmetrical pRNFL loss and the location and gravity of VF loss at initial presentation in young myopic glaucomatous-appearing patients. These findings are clinically important for initial detection and planning the follow up strategy in myopic glaucomatous-appearing eyes with different disc tilt directions. PMID- 27552519 TI - Puerarin Attenuates N-Methyl-D-aspartic Acid-induced Apoptosis and Retinal Ganglion Cell Damage Through the JNK/p38 MAPK Pathway. AB - PURPOSE: To explore the protective effect of puerarin on N-methyl-D-aspartic acid (NMDA)-induced retinal ganglion cells (RGCs) injury and its underlying mechanism. MATERIALS AND METHODS: Primary RGCs were isolated from P3-P7 Sprague-Dawley rats and purified by sequential immunopanning using Thy1.1 antibodies. NMDA was used to mimic the glutamate activation, cell apoptosis, reactive oxygen species (ROS), malondialdehyde levels, SOD and NO production, nNOS and iNOS expression, as well as caspase-3 activity, Bcl-2, and Bax expression in the RGCs were analyzed by ELISA, RT-PCR, and Western blotting. A rat model of retinal injury was used to detect the protective effect of puerarin. RESULTS: Puerarin protected against NMDA-induced RGCs injury in a dose-dependent manner. Compared with the NMDA treated group, puerarin pretreatment significantly reduced ROS and malondialdehyde levels, promoted SOD and NO production, and downregulated nNOS and iNOS expression in the RGCs. Mechanism analysis showed that pretreatment with puerarin could effectively offset the increase of Bax expression and caspase-3 activity brought by NMDA, and promote Bcl-2 expression in the RGCs. Puerarin pretreatment also effectively inhibited NMDA-induced JNK and p38 phosphorylation in the RGCs, whereas pretreatment with either JNK agonist anisomycin or p38 agonist P79350 could significantly compensate the effects caused by puerarin. Furthermore, puerarin prevented RGCs loss in the retinal injury induced by intravitreal NMDA in a rat model. CONCLUSIONS: The present results of this study demonstrated that puerarin protected against NMDA-induced apoptosis and RGCs damage through the JNK/p38 MAPK pathway. PMID- 27552520 TI - Total Structure Determination of Au21(S-Adm)15 and Geometrical/Electronic Structure Evolution of Thiolated Gold Nanoclusters. AB - The larger size gold nanoparticles typically adopt a face-centered cubic (fcc) atomic packing, while in the ultrasmall nanoclusters the packing styles of Au atoms are diverse, including fcc, hexagonal close packing (hcp), and body centered cubic (bcc), depending on the ligand protection. The possible conversion between these packing structures is largely unknown. Herein, we report the growth of a new Au21(S-Adm)15 nanocluster (S-Adm = adamantanethiolate) from Au18(SR)14 (SR = cyclohexylthiol), with the total structure determined by X-ray crystallography. It is discovered that the hcp Au9-core in Au18(SR)14 is transformed to a fcc Au10-core in Au21(S-Adm)15. Combining with density functional theory (DFT) calculations, we provide critical information about the growth mechanism (geometrical and electronic structure) and the origin of fcc structure formation for the thiolate-protected gold nanoclusters. PMID- 27552521 TI - Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. AB - BACKGROUND: Kangaroo mother care (KMC), originally defined as skin-to-skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants. OBJECTIVES: To determine whether evidence is available to support the use of KMC in LBW infants as an alternative to conventional neonatal care before or after the initial period of stabilization with conventional care, and to assess beneficial and adverse effects. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches in CENTRAL (Cochrane Central Register of Controlled Trials; 2016, Issue 6), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILACS (Latin American and Caribbean Health Science Information database), and POPLINE (Population Information Online) databases (all from inception to June 30, 2016), as well as the WHO (World Health Organization) Trial Registration Data Set (up to June 30, 2016). In addition, we searched the web page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and Google Scholar. SELECTION CRITERIA: Randomized controlled trials comparing KMC versus conventional neonatal care, or early-onset KMC versus late-onset KMC, in LBW infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-one studies, including 3042 infants, fulfilled inclusion criteria. Nineteen studies evaluated KMC in LBW infants after stabilization, one evaluated KMC in LBW infants before stabilization, and one compared early-onset KMC with late-onset KMC in relatively stable LBW infants. Sixteen studies evaluated intermittent KMC, and five evaluated continuous KMC. KMC versus conventional neonatal care: At discharge or 40 to 41 weeks' postmenstrual age, KMC was associated with a statistically significant reduction in the risk of mortality (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.39 to 0.92; eight trials, 1736 infants), nosocomial infection/sepsis (RR 0.35, 95% CI 0.22 to 0.54; five trials, 1239 infants), and hypothermia (RR 0.28, 95% CI 0.16 to 0.49; nine trials, 989 infants; moderate quality evidence). At latest follow-up, KMC was associated with a significantly decreased risk of mortality (RR 0.67, 95% CI 0.48 to 0.95; 12 trials, 2293 infants; moderate-quality evidence) and severe infection/sepsis (RR 0.50, 95% CI 0.36 to 0.69; eight trials, 1463 infants; moderate-quality evidence). Moreover, KMC was found to increase weight gain (mean difference [MD] 4.1 g/d, 95% CI 2.3 to 5.9; 11 trials, 1198 infants; moderate-quality evidence), length gain (MD 0.21 cm/week, 95% CI 0.03 to 0.38; three trials, 377 infants) and head circumference gain (MD 0.14 cm/week, 95% CI 0.06 to 0.22; four trials, 495 infants) at latest follow-up, exclusive breastfeeding at discharge or 40 to 41 weeks' postmenstrual age (RR 1.16, 95% CI 1.07 to 1.25; six studies, 1453 mothers) and at one to three months' follow-up (RR 1.20, 95% CI 1.01 to 1.43; five studies, 600 mothers), any (exclusive or partial) breastfeeding at discharge or at 40 to 41 weeks' postmenstrual age (RR 1.20, 95% CI 1.07 to 1.34; 10 studies, 1696 mothers; moderate-quality evidence) and at one to three months' follow-up (RR 1.17, 95% CI 1.05 to 1.31; nine studies, 1394 mothers; low-quality evidence), and some measures of mother-infant attachment and home environment. No statistically significant differences were found between KMC infants and controls in Griffith quotients for psychomotor development at 12 months' corrected age (low-quality evidence). Sensitivity analysis suggested that inclusion of studies with high risk of bias did not affect the general direction of findings nor the size of the treatment effect for main outcomes. Early-onset KMC versus late-onset KMC in relatively stable infants: One trial compared early-onset continuous KMC (within 24 hours post birth) versus late-onset continuous KMC (after 24 hours post birth) in 73 relatively stable LBW infants. Investigators reported no significant differences between the two study groups in mortality, morbidity, severe infection, hypothermia, breastfeeding, and nutritional indicators. Early-onset KMC was associated with a statistically significant reduction in length of hospital stay (MD 0.9 days, 95% CI 0.6 to 1.2). AUTHORS' CONCLUSIONS: Evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care, mainly in resource-limited settings. Further information is required concerning the effectiveness and safety of early-onset continuous KMC in unstabilized or relatively stabilized LBW infants, as well as long-term neurodevelopmental outcomes and costs of care. PMID- 27552522 TI - Instruments for assessing readiness to commence suck feeds in preterm infants: effects on time to establish full oral feeding and duration of hospitalisation. AB - BACKGROUND: One of the most challenging milestones for preterm infants is the acquisition of safe and efficient feeding skills. The majority of healthy full term infants are born with skills to coordinate their suck, swallow and respiration. However, this is not the case for preterm infants who develop these skills gradually as they transition from tube feeding to suck feeds. For preterm infants the ability to engage in oral feeding behaviour is dependent on many factors. The complexity of factors influencing feeding readiness has led some researchers to investigate the use of an individualised assessment of an infant's abilities. A limited number of instruments that aim to indicate an individual infant's readiness to commence either breast or bottle feeding have been developed. OBJECTIVES: To determine the effects of using a feeding readiness instrument when compared to no instrument or another instrument on the outcomes of time to establish full oral feeding and duration of hospitalisations. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 22 February 2016), EMBASE (1980 to 22 February 2016), and CINAHL (1982 to 22 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing a formal instrument to assess a preterm infant's readiness to commence suck feeds with either no instrument (usual practice) or another feeding readiness instrument. DATA COLLECTION AND ANALYSIS: The standard methods of Cochrane Neonatal were used. Two authors independently screened potential studies for inclusion. No studies were found that met our inclusion criteria. MAIN RESULTS: No studies met the inclusion criteria. AUTHORS' CONCLUSIONS: There is currently no evidence to inform clinical practice, with no studies meeting the inclusion criteria for this review. Research is needed in this area to establish an evidence base for the clinical utility of implementing the use of an instrument to assess feeding readiness in the preterm infant population. PMID- 27552523 TI - Association of olfactory dysfunction in chronic rhinosinusitis with economic productivity and medication usage. AB - BACKGROUND: Chronic rhinosinusitis (CRS) has significant impacts upon productivity, economic metrics, and medication usage; however, factors that are associated with these economic outcomes are unknown. METHODS: We evaluated olfactory dysfunction in 221 patients with CRS using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) and the 40-item Smell Identification Test (SIT) and assessed whether an association existed between these olfactory metrics and healthcare utilization, productivity, and medication usage over the preceding 90 days. RESULTS: After adjusting for CRS-associated comorbidities, objective measures of disease, demographics, and CRS-specific quality of life (QOL), patients with lower QOD-NS scores (worse patient-reported olfaction) had more missed days of normal productivity and employment, worse productivity levels, more hours of missed employment due to physician visits, more time caring for sinuses, greater distance traveled to medical appointment, more days of oral steroid use, and higher odds of being on disability insurance. Clinical olfaction, as measured by SIT, was associated with greater distance traveled to medical appointment and higher odds of being on disability insurance, but did not correlate with other productivity measures. CONCLUSION: Impaired olfactory-specific QOL is associated with significantly worse economic and productivity metrics and increased medication usage even after adjusting for CRS specific comorbidities, objective measures of disease, demographics, and severity of CRS-specific QOL. Future studies are warranted to determine if targeting the impaired olfactory-specific QOL noted in patients with CRS results in improved productivity and economic outcomes. PMID- 27552524 TI - Formoterol fumarate + glycopyrrolate for the treatment of chronic obstructive pulmonary disease. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by a high disability and increasing mortality. Bronchodilators are the cornerstone of pharmacological treatment in COPD, while therapeutic optimization with an improvement in symptoms and compliance represent the actual goals. This has led to the development of devices that combine different classes of inhalatory drugs. Recently, a novel combination of the long acting antimuscarinic agent glycopyrronium bromide and the beta2-agonist formoterol fumarate has been developed in a metered dose inhaler delivery system. AREAS COVERED: The present article will discuss the current unmet needs in pharmacological therapy of COPD, will then briefly cover the pharmacokinetic and pharmacodynamic characteristics of the formoterol/glycopyrronium fixed dose combination and present the novel delivery system based on engineered microparticles and the co-suspension technology. Finally, efficacy and safety results of phase I, II and III trials will be reviewed. Expert commentary: The novel combination therapy of formoterol/glycopyrronium is the first available as a metered dose inhaler and proved to have a good efficacy and safety profile compared to monocomponents and tiotropium. Although still limited, data from phase III trials provide good evidence to consider it a valid option in the pharmacological management of patients with COPD. PMID- 27552525 TI - Improving All-Inorganic Perovskite Photodetectors by Preferred Orientation and Plasmonic Effect. AB - All-inorganic perovskites have high carrier mobility, long carrier diffusion length, excellent visible light absorption, and well overlapping with localized surface plasmon resonance (LSPR) of noble metal nanocrystals (NCs). The high performance photodetectors can be constructed by means of the intrinsic outstanding photoelectric properties, especially plasma coupling. Here, for the first time, inorganic perovskite photodetectors are demonstrated with synergetic effect of preferred-orientation film and plasmonic with both high performance and solution process virtues, evidenced by 238% plasmonic enhancement factor and 106 on/off ratio. The CsPbBr3 and Au NC inks are assembled into high-quality films by centrifugal-casting and spin-coating, respectively, which lead to the low cost and solution-processed photodetectors. The remarkable near-field enhancement effect induced by the coupling between Au LSPR and CsPbBr3 photogenerated carriers is revealed by finite-difference time-domain simulations. The photodetector exhibits a light on/off ratio of more than 106 under 532 nm laser illumination of 4.65 mW cm-2 . The photocurrent increases from 0.67 to 2.77 MUA with centrifugal-casting. Moreover, the photocurrent rises from 245.6 to 831.1 MUA with Au NCs plasma enhancement, leading to an enhancement factor of 238%, which is the most optimal report among the LSPR-enhanced photodetectors, to the best of our knowledge. The results of this study suggest that all-inorganic perovskites are promising semiconductors for high-performance solution-processed photodetectors, which can be further enhanced by Au plasmonic effect, and hence have huge potentials in optical communication, safety monitoring, and biological sensing. PMID- 27552527 TI - Corrigendum. PMID- 27552526 TI - Corrigendum. PMID- 27552528 TI - Phonon-Enabled Carrier Transport of Localized States at Non-Polar Semiconductor Surfaces: A First-Principles-Based Prediction. AB - Electron-phonon coupling can hamper carrier transport either by scattering or by the formation of mass-enhanced polarons. Here, we use time-dependent density functional theory-molecular dynamics simulations to show that phonons can also promote the transport of excited carriers. Using nonpolar InAs (110) surface as an example, we identify phonon-mediated coupling between electronic states close in energy as the origin for the enhanced transport. In particular, the coupling causes localized excitons in the resonant surface states to propagate into bulk with velocities as high as 10(6) cm/s. The theory also predicts temperature enhanced carrier transport, which may be observable in ultrathin nanostructures. PMID- 27552529 TI - Results from Screening Polyurethane Foam Based Consumer Products for Flame Retardant Chemicals: Assessing Impacts on the Change in the Furniture Flammability Standards. AB - Flame retardant (FR) chemicals have often been added to polyurethane foam to meet required state and federal flammability standards. However, some FRs (e.g., PBDEs and TDCIPP) are associated with health hazards and are now restricted from use in some regions. In addition, California's residential furniture flammability standard (TB-117) has undergone significant amendments over the past few years, and TDCIPP has been added to California's Proposition 65 list. These events have likely led to shifts in the types of FRs used, and the products to which they are applied. To provide more information on the use of FRs in products containing polyurethane foam (PUF), we established a screening service for the general public. Participants residing in the US were allowed to submit up to 5 samples from their household for analysis, free of charge, and supplied information on the product category, labeling, and year and state of purchase. Between February 2014 and June 2016, we received 1141 PUF samples for analysis from various products including sofas, chairs, mattresses, car seats and pillows. Of these samples tested, 52% contained a FR at levels greater than 1% by weight. Tris(1,3 dichloroisopropyl)phosphate (TDCIPP) was the most common FR detected in PUF samples, and was the most common FR detected in all product categories. Analysis of the data by purchasing date suggests that the use of TDCIPP decreased in recent years, paralleled with an increase in the use of TCIPP and a nonhalogenated aryl phosphate mixture we call "TBPP." In addition, we observed significant decreases in FR applications in furniture products and child car seats, suggesting the use of additive FRs in PUF may be declining, perhaps as a reflection of recent changes to TB-117 and Proposition 65. More studies are needed to determine how these changes in FR use relate to changes in exposure among the general population. PMID- 27552530 TI - Effects of Cognitive Distortions on the Link Between Dating Violence Exposure and Substance Problems in Clinically Hospitalized Youth. AB - PURPOSE: The purpose of the present study was to examine whether cognitive distortions (e.g., cognitive errors; negative views of self, world, and future) influence the association between dating violence and problematic substance use behaviors in a sample of psychiatrically hospitalized adolescents. METHOD: Participants included 155 adolescents, aged 13-17 years, who had initiated dating. Adolescents completed measures of dating violence, substance-related problems (alcohol and marijuana), and cognitive distortions. RESULTS: Logistic regressions were conducted to examine the direct and interactive effects of dating violence exposure and cognitive distortions on likelihood of recent problematic substance use. Results suggested a main effect of dating violence on problematic alcohol and other drug use as well as an interactive effect of dating violence and cognitive distortions. Specifically, the relationship between dating violence and odds of substance-related problems was higher among those with greater (vs. fewer) cognitive distortions. CONCLUSION: Study results suggest the need for careful screening of cognitive distortions among adolescent dating violence victims, particularly those in mental health treatment. PMID- 27552531 TI - Suicide risk and suicide method in patients with personality disorders. AB - OBJECTIVE: The influence of psychopathology on suicide method has revealed different distributions among different psychiatric disorders. However, evidence is still scarce. We hypothesized that having a diagnosis of personality disorder (PD) affect the suicide method, and that different PD clusters would influence the suicide method in different ways. In addition, we hypothesized that the presence of psychiatric and somatic co-morbidity also affects the suicide method. METHOD: We examined 25,217 individuals aged 15-64 who had been hospitalized in Sweden with a main diagnosis of PD the years 1987-2013 (N = 25,217). The patients were followed from the date of first discharge until death or until the end of the follow-up period, i.e. December 31, 2013, for a total of 323,508.8 person years, with a mean follow up time of 11.7 years. The SMR, i.e. the ratio between the observed number of suicides and the expected number of suicides, was used as a measure of risk. RESULTS: Overall PD, different PD-clusters, and comorbidity influenced the suicide method. Hanging evidenced highest SMR in female PD patients (SMR 34.2 (95% CI: 29.3-39.8)), as compared to non-PD patients and jumping among male PD patients (SMR 24.8 (95% CI: 18.3-33.6)), as compared to non PD-patients. Furthermore, the elevated suicide risk was related to both psychiatric and somatic comorbidity. CONCLUSION: The increased suicide risk was unevenly distributed with respect to suicide method and type of PD. However, these differences were only moderate and greatly overshadowed by the overall excess suicide risk in having PD. Any attempt from society to decrease the suicide rate in persons with PD must take these characteristics into account. PMID- 27552534 TI - Work motivation in health care: a scoping literature review. AB - AIM: The aim of this scoping literature review was to examine and summarize the factors, context, and processes that influence work motivation of health care workers. METHODS: A scoping literature review was done to answer the question: What is known from the existing empirical literature about factors, context, and processes that influence work motivation of health care workers? This scoping review used the Arksey and O'Malley framework to describe and summarize findings. Inclusion and exclusion criteria were developed to screen studies. Relevant studies published between January 2005 and May 2016 were identified using five electronic databases. Study abstracts were screened for eligibility by two reviewers. Following this screening process, full-text articles were reviewed to determine the eligibility of the studies. Eligible studies were then evaluated by coding findings with descriptive labels to distinguish elements that appeared pertinent to this review. Coding was used to form groups, and these groups led to the development of themes. RESULTS: Twenty-five studies met the eligibility criteria for this literature review. The themes identified were work performance, organizational justice, pay, status, personal characteristics, work relationships (including bullying), autonomy, organizational identification, training, and meaningfulness of work. CONCLUSION: Most of the research involved the use of surveys. There is a need for more qualitative research and for the use of case studies to examine work motivation in health care organizations. All of the studies were cross-sectional. Longitudinal research would provide insight into how work motivation changes, and how it can be influenced and shaped. Several implications for practice were identified. There is a need to ensure that health care workers have access to training opportunities, and that autonomy is optimized. To improve work motivation, there is a need to address bullying and hostile behaviours in the workplace. Addressing the factors that influence work motivation in health care settings has the potential to influence the care that patients receive. PMID- 27552533 TI - Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study. AB - OBJECTIVE: We performed a systematic review and meta-analysis to estimate brain derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT). METHOD: A comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: "major depressive disorder", "unipolar depression", "brain derived neurotrophic factor", and "electroconvulsive therapy". RESULTS: A total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17-0.96). Additionally, we found significant heterogeneity between studies (I2 = 73%). CONCLUSION: Our findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD. PMID- 27552535 TI - The impact of pharmacists' input to reduce serotonin syndrome drug interactions in an Australian hospital. AB - BACKGROUND: Drug interactions contribute significantly to adverse-related events and hospital admissions. Example of common drug interactions includes combinations of medications that induces serotonin syndrome. Pharmacists are well placed in the multidisciplinary team to alert prescribers of these drug interactions and offer an alternative management. OBJECTIVE: The objective is to evaluate the effectiveness of pharmacists' input in preventing patients being discharged on clinically relevant drug interactions that have the potential to cause serotonin syndrome in an Australian hospital. METHOD: A retrospective cross sectional audit of patients' case notes who were prescribed a combination of drugs likely to induce serotonin syndrome on admission were examined over a 3 month period. A predefined list of serotonin syndrome-inducing drugs of severity 1 and 2 was used to search for patients on these drug combinations on admission. The severities of the drug combinations were classified as per the Monthly Index of Medical Specialties drug interactions guide. Subsequent pharmacists' interventions were recorded on discharge to observe any change in prescribing practice. Descriptive statistics were used to analyze the data. P values were obtained using the Student's t-test and Fisher's exact tests. RESULTS: A total of 144 patients over 3 months were identified to have been prescribed a combination of drugs with a potential to cause serotonin syndrome during admission. Of these patients, 79 and 21% were prescribed combination of serotonergic drugs that were classified as severity 1 and 2, respectively, according to Monthly Index of Medical Specialties. A total of 56% (n = 81) of the audited patients were discharged with no serotonin syndrome-inducing drug combinations and 44% (n = 63) were discharged on serotonin syndrome-inducing drug combinations of severity 1 or 2. Pharmacist input has led to a significant reduction (relative risk reduction 44%; P < 0.0001) in the total number of patients who were discharged on severity 1 and 2 serotonin syndrome-inducing drug combinations. There were 87 patients (60%) who had a pharmacist input during admission. In this subset of the cohort, 36% (n = 31) of patients were discharged on serotonin syndrome-inducing drug combinations (combined both severity 1 and 2) compared with 56% (n = 32) in those who did not get a pharmacist input, P = 0.017. In addition, 64% (n = 56) of patients in this group were discharged on no serotonin syndrome-inducing drug combinations compared with 44% (n = 25) in the nonpharmacist group, P = 0.017. CONCLUSION: The audit highlights the pharmacists' role in significantly reducing clinically relevant drug interaction in patients prescribed serotonin syndrome inducing drug combination in a single-center Australian hospital on discharge. PMID- 27552536 TI - Improving medication safety: let's make consumer engagement central. PMID- 27552537 TI - Transmitted irradiance not as expected in enclosed handheld minimal erythema dose device. PMID- 27552538 TI - Vitamin D Receptor Down-Regulation Is Associated With Severity of Albuminuria in Type 2 Diabetes Patients. AB - CONTEXT: Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities. OBJECTIVE: To investigate the correlation between VDR expression and albuminuria in T2DM. DESIGN/SETTING/PATIENTS: Renal biopsies from T2DM patients with albuminuria (n = 8) and nondiabetic subjects (n = 4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n = 242; estimated glomerular filtration rate > 60 mL/min/1.73 m2) were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR < 30 mg/g; n = 85), microalbuminuria (30 mg/g <= uACR < 300 mg/g; n = 84), and macroalbuminuria (uACR >= 300 mg/g; n = 73), with healthy individuals (n = 72) as controls. Peripheral blood mononuclear cells (PBMCs) from these subjects were analyzed for VDR mRNA (n = 314), TNF-alpha mRNA (n = 314), microRNA (miR)-346 (n = 120; 30 for each group), and VDR protein (n = 80; 20 for each group). PBMCs from randomly selected subjects (n = 6 for each group) were cultured ex vivo to evaluate the effect of TNF-alpha on miR-346 and VDR, and miR-346-mediated VDR suppression was further explored in HK2 cells. RESULTS: VDR expression was down regulated in PBMCs and renal tubular epithelial cells from T2DM patients with albuminuria. VDR mRNA and protein levels were both negatively correlated with uACR, and VDR mRNA was inversely correlated with TNF-alpha and miR-346 in PBMCs from T2DM patients. TNF-alpha reduced VDR while inducing miR-346 in cultured PBMCs. TNF-alpha suppressed VDR by up-regulating miR-346 in HK2 cells. CONCLUSIONS: VDR down-regulation in PBMCs is independently associated with the severity of albuminuria in T2DM. TNF-alpha suppression of VDR in PBMCs and HK2 cells is mediated by miR-346. PMID- 27552532 TI - Transdiagnostic impairment of cognitive control in mental illness. AB - Intact cognitive control or executive function has characteristic patterns in both behavior and functional neurocircuitry. Functional neuroimaging studies have shown that a frontal-cingulate-parietal-insular (i.e., "multiple demand") network forms a common functional substrate undergirding successful adaptation to diverse cognitive processing demands. Separate work on intact neurocognitive performance implicates a higher order factor that largely explains performance across domains and may reflect trait cognitive control capacity. In the current review we highlight findings from respective psychiatric disorders (i.e., psychotic, bipolar and unipolar depressive, anxiety, and substance use disorders) suggesting that cognitive control perturbations amidst psychopathology are most pronounced within these common brain and behavioral indices of adaptive cognitive functioning and moreover, are evident across disorders (i.e., transdiagnostically). Specifically, within each of the disorder classes impairments are consistent in the multiple demand network across a wide range of cognitive tasks. While severity varies between disorders, broad as opposed to domain-specific impairments consistently emerge in neurocognitive performance. Accumulating findings have revealed that phenotypically diverse psychiatric disorders share a common factor or vulnerability to dysfunction that is in turn related to broad neurocognitive deficits. Furthermore, we have observed that regions of the multiple demand network, which overlap with the salience network (dorsal anterior cingulate and bilateral anterior insula) are characterized by reduced gray matter transdiagnostically and predict weaker neurocognitive performance. In summary, transdiagnostic (as opposed to disorder-specific) patterns of symptomatic distress and neurocognitive performance deficits, concurrent with parallel anomalies of brain structure and function may largely contribute to the real-world socio-occupational impairment common across disorders. PMID- 27552540 TI - Vascular Health in Patients in Remission of Cushing's Syndrome Is Comparable With That in BMI-Matched Controls. AB - CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant because this topic relates to future development of cardiovascular disease. OBJECTIVE: The objective of the study was to investigate whether micro- and macrovascular health is impaired after long-term remission of CS in patients with no or adequately treated comorbidities. DESIGN AND SETTING: This was a cross sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: Sixty-three patients (remission of CS for >= 4 y) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls), serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity, and pulse wave analysis were studied. In group B (14 patients and 14 controls), endothelium-dependent and -independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intraarterial acetylcholine, sodium-nitroprusside, and NG-monomethyl L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in groups A and B. CONCLUSION: The vascular health of patients in long-term remission of CS seems to be comparable with that of healthy gender-, age-, and body mass index-matched controls, provided that the patients have no, or adequately controlled, comorbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for the stringent treatment of metabolic comorbidities in these patients. PMID- 27552539 TI - Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). AB - CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research. PMID- 27552541 TI - Bone Mineral Density and Progression of Subclinical Atherosclerosis in African Americans With Type 2 Diabetes. AB - CONTEXT: Relative to European Americans, calcified atherosclerotic plaque (CP) is less prevalent and severe in African-Americans (AAs). OBJECTIVE: Predictors of progression of CP in the aorta, carotid, and coronary arteries were examined in AAs over a mean 5.3 +/- 1.4-year interval. DESIGN: This is the African American Diabetes Heart Study. SETTING: A type 2 diabetes (T2D)-affected cohort was included. PARTICIPANTS: A total of 300 unrelated AAs with T2D; 50% female, mean age 55 +/- 9 years, baseline hemoglobin A1c 8.1 +/- 1.8% was included. MAIN OUTCOME MEASURES: Glycemic control, renal parameters, vitamin D, and computed tomography-derived measures of adiposity, vascular CP, and volumetric bone mineral density (vBMD) in lumbar and thoracic vertebrae were obtained at baseline and follow-up. RESULTS: CP increased in incidence and quantity/mass in all three vascular beds over the 5-year study (P < .0001). Lower baseline lumbar and thoracic vBMD were associated with progression of abdominal aorta CP (P < .008), but not progression of carotid or coronary artery CP. Lower baseline estimated glomerular filtration rate was associated with progression of carotid artery CP (P = .0004), and higher baseline pericardial adipose volume was associated with progression of coronary artery (P = .001) and aorta (P = .0006) CP independent of body mass index. There was a trend for an inverse relationship between change in thoracic vBMD and change in aortic CP (P = .05). CONCLUSIONS: In this longitudinal study, lower baseline thoracic and lumbar vBMD and estimated glomerular filtration rate and higher pericardial adipose volumes were associated with increases in CP in AAs with T2D. Changes in these variables and baseline levels and/or changes in glycemic control, albuminuria, and vitamin D were not significantly associated with progression of CP. PMID- 27552542 TI - Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study. AB - CONTEXT: Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood. OBJECTIVE: This study sought to determine whether thyroid hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds. DESIGN: A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years. SETTING AND PARTICIPANTS: Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom. MAIN OUTCOMES: All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT4, FT3, and rT3). Models were adjusted for age, sex, education, body mass index, smoking, and disease count. RESULTS: After adjustment for age and sex, all-cause mortality was associated with baseline serum rT3 and FT3 (both P < .001), but not FT4 or TSH. After additional adjustment for potential confounders, only rT3 remained significantly associated with mortality (P = .001). Baseline serum TSH and rT3 predicted future disability trajectories in men and women, respectively. CONCLUSIONS: Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serum TSH levels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges. PMID- 27552543 TI - Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures. AB - CONTEXT: Established bone turnover markers do not reflect fracture risk in idiopathic male and premenopausal osteoporosis and the role of microRNAs (miRNAs) in these patients is currently unclear. miRNAs are a class of small non-coding RNAs that regulate gene expression and bone tissue homeostasis. They are considered a new class of endocrine regulators with promising potential as biomarkers. OBJECTIVE: Evaluation of circulating miRNA signatures in male and female subjects with idiopathic and postmenopausal osteoporotic low-traumatic fractures. DESIGN, SETTING, AND PATIENTS: This was a case-control study of cross sectional design of 36 patients with prevalent low-traumatic fractures and 39 control subjects Main Outcome Measures: One hundred eighty-seven miRNAs were quantified in serum by qPCR, compared between groups and correlated with established bone turnover markers. RESULTS: Significant differences in serum levels of circulating miRNAs were identified in all three subgroups (46 in premenopausal, 52 in postmenopausal, 55 in male). A set of 19 miRNAs was consistently regulated in all three subgroups. Eight miRNAs [miR-152-3p, miR-30e 5p, miR-140-5p, miR-324-3p, miR-19b-3p, miR-335-5p, miR-19a-3p, miR-550a-3p] were excellent discriminators of patients with low-traumatic fractures, regardless of age and sex, with area under the curve values > 0.9. The 11 remaining miRNAs showed area under the curve values between 0.81 and 0.89. Correlation analysis identified significant correlations between miR-29b-3p and P1NP, and miR-365-5p and iPTH, TRAP5b, P1NP and Osteocalcin, as well as BMDL1-L4 and miR-19b-3p, miR 324-3p, miR-532-5p, and miR-93-5p. CONCLUSIONS: Specific serum miRNA profiles are strongly related to bone pathologies. Therefore miRNAs might be directly linked to bone tissue homeostasis. In particular, miR-29b-3p has previously been reported as regulator of osteogenic differentiation and could serve as a novel marker of bone turnover in osteoporotic patients as a member of a miRNA signature. PMID- 27552544 TI - Obesity Severity and Duration Are Associated With Incident Metabolic Syndrome: Evidence Against Metabolically Healthy Obesity From the Multi-Ethnic Study of Atherosclerosis. AB - CONTEXT: Although the health risks of obesity compared to normal weight have been well studied, the cumulative risk associated with chronic obesity remains unknown. Specifically, debate continues about the importance of recommending weight loss for those with metabolically healthy obesity. OBJECTIVE: We hypothesized that relatively greater severity and longer duration of obesity are associated with greater incident metabolic syndrome. Design, Setting, Participants, and Measures: Using repeated measures logistic regression with random effects, we investigated the association of time-varying obesity severity and duration with incident metabolic syndrome in 2,748 Multi-Ethnic Study of Atherosclerosis participants with obesity (body mass index >=30 kg/m2) at any visit. Obesity duration was defined as the cumulative number of visits with measured obesity and obesity severity by the World Health Organization levels I III based on body mass index. Metabolic syndrome was defined using Adult Treatment Panel III criteria modified to exclude waist circumference. RESULTS: Higher obesity severity (level II odds ratio [OR], 1.32 [95% confidence interval, 1.09-1.60]; level III OR, 1.63 [1.25-2.14] vs level I) and duration (by number of visits: two visits OR, 4.43 [3.54-5.53]; three visits OR, 5.29 [4.21-6.63]; four visits OR, 5.73 [4.52-7.27]; five visits OR, 6.15 [4.19-9.03] vs one visit duration of obesity) were both associated with a higher odds of incident metabolic syndrome. CONCLUSION: Both duration and severity of obesity are positively associated with incident metabolic syndrome, suggesting that metabolically healthy obesity is a transient state in the pathway to cardiometabolic disease. Weight loss should be recommended to all individuals with obesity, including those who are currently defined as metabolically healthy. PMID- 27552545 TI - Beneficial Effects of GH in Young Adults With Prader-Willi Syndrome: A 2-Year Crossover Trial. AB - CONTEXT: Patients with Prader-Willi syndrome (PWS) are severely at risk to develop morbid obesity, diabetes mellitus type 2, and cardiovascular disease, leading to high mortality. They have an increased fat mass (FM) and decreased lean body mass (LBM). During childhood, GH treatment counteracts the natural course of increasing obesity. Discontinuation of GH treatment at attainment of adult height (AH) might deteriorate their improved clinical condition, whereas continuation might benefit them. OBJECTIVE: To investigate the effects of GH versus placebo on body composition in young adults with PWS who were GH treated for many years during childhood and had attained AH. DESIGN: Two-year, randomized, double-blind, placebo-controlled crossover study with stratification for gender and body mass index in 27 young adults with PWS. SETTING: PWS Reference Center in The Netherlands. INTERVENTION: Crossover intervention with GH (0.67 mg/m2 . d) and placebo, both during 1 year. MAIN OUTCOME MEASURES: Body composition, measured by dual-energy x-ray absorptiometry. RESULTS: During placebo, FM increased (relative change +21.5%; P < .001). Compared with placebo, GH treatment resulted in lower FM (-2.9 kg; P = .004) and higher LBM (+1.5 kg; P = .005), representing relative changes of -17.3% FM and +3.5% LBM. Both limb and trunk FM percentage were lower during GH versus placebo (relative change +17.3% and +15.6%; P < .001 and P = .007, respectively). No GH-related adverse events occurred. CONCLUSIONS: GH-treated young adults with PWS who have attained AH benefit from continuation of GH treatment. FM increases during placebo, whereas GH versus placebo results in lower FM and higher LBM. Thus, GH treatment maintains the improved body composition without safety concerns. PMID- 27552546 TI - Induction of regulatory T cells by Opisthorchis viverrini. AB - Opisthorchis viverrini causes public health problems in South-East Asia. Recently, TGF-beta and IL-10 have been reported to increase in O. viverrini infected hamsters but the sources of these cytokines are still unknown. In this study, the CD4+ T cells in infected hamsters were investigated. It was demonstrated that IL-4+ CD4+ T cells were significantly increased in hamster spleens and mesenteric lymph nodes (MLNs) during chronic infection. Interestingly, IL-10+ CD4+ T cells were also discovered at a significant level while Treg (T regulatory)-like TGF- beta+ CD4+ T cells were in MLNs of infected hamsters. Moreover, the CD4+ CD25+ Foxp3+ Treg cell response was significantly found both in spleens and MLNs in infected hamsters. The findings were then confirmed by development of T-cell clones against crude somatic antigens (CSAg) in immunized BALB/c mice. Five clones named TCC21, TCC23, TCC35, TCC41 and TCC108 were established. The TCC21 was found to be the TGF-beta+ CD4+ while TCC35, TCC41 and TCC108 were IL-4+ CD4+ and TCC23 was IFN-gamma+ CD4+ . This TGF-beta+ CD4+ T clone showed an inhibitory function in vitro in mononuclear cell proliferation via TGF-beta-mediated mechanisms. This study indicated that O. viverrini-infected hamsters could induce TGF-beta+ CD4+ Treg-like cells. The CSAg-specific Tregs secreted high TGF-beta, and limited immune cell proliferation. PMID- 27552547 TI - Peritoneal Macrophage-Specific TNF-alpha Gene Silencing in LPS-Induced Acute Inflammation Model Using CD44 Targeting Hyaluronic Acid Nanoparticles. AB - The main goal of this study was to evaluate tumor necrosis factor-alpha (TNF alpha) gene silencing in peritoneal macrophages upon activation with lipopolysaccharide (LPS), using CD44-targeting hyaluronic acid (HA)-based nanoparticles encapsulating TNF-alpha-specific small interfering RNA (siTNF alpha). HA nanoparticles were formulated by blending hyaluronic acid poly(ethylene imine) (HA-PEI), hyaluronic acid-hexyl fatty acid (HA-C6), and hyaluronic acid-poly(ethylene glycol) (HA-PEG) in 3:2:1 weight ratio, and encapsulating siTNF-alpha to form spherical particles of 78-90 nm diameter. Following intraperitoneal (IP) administration in LPS-treated C57BL/6 mice, the nanoparticles were actively taken up by macrophages and led to a significant downregulation of peritoneal TNF-alpha level. Downregulation of peritoneal macrophage-specific TNF-alpha also had a significant impact on other pro inflammatory cytokine and chemokine levels in the serum. The C57BL/6 group of mice challenged with 5 mg/kg LPS had a significantly higher survival rate when they were treated with 3 mg/kg siTNF-alpha, either prior or simultaneously with the LPS administration, as compared to the LPS-challenged mice, which were treated with controls including the scrambled siRNA formulation. Overall, the results of this study demonstrate that CD44 targeting HA nanoparticles can selectively deliver siTNF-alpha to peritoneal macrophages leading to downregulation of pro-inflammatory cytokines in the peritoneal fluid and in the serum. This RNAi strategy could potentially provide an important therapeutic modality for acute inflammatory diseases, such as septic shock. PMID- 27552548 TI - Promoting retention, enabling success: Discovering the potential of student support circles. AB - Retention of students is critical to education programs and future workforce. A mixed methods study evaluated student engagement within a Bachelor of Midwifery program and connection with career choice through participation in student support circles. Centred on the Five Senses of Success Framework (sense of capability, purpose, identity, resourcefulness and connectedness) and including four stages of engagement (creating space, preparing self, sharing stories, focused conversations), the circles support and develop student and professional identity. Of 80 students 43 (54%) provided responses to a two item survey assessed against a five point Likert scale to determine utility. Using a nominal group technique, student's voices gave rich insight into the personal and professional growth that participation in the student support circles provided. Evaluated as helpful to first year students in orientating to university study and early socialisation into the profession, the circles appear to influence the development of a strong sense of professional identity and personal midwifery philosophy based on the relational nature of the midwife being with woman rather than doing midwifery. This suggests that student support circles positively influence perceptions and expectations, contributing to a shared sense of purpose and discipline connection, for enhancing student retention and future workforce participation. PMID- 27552549 TI - Corrigendum: Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles. PMID- 27552550 TI - Corrigendum: A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4 Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile. PMID- 27552551 TI - Corrigendum: Noncovalent Hydrogel Beads as Microcarriers for Cell Culture. PMID- 27552554 TI - News & Announcements: American Society for Laser Medicine & Surgery, Inc. PMID- 27552553 TI - Quality of life of HIV-infected patients who switch antiretroviral medication due to side effects or other reasons. AB - OBJECTIVE: The objective of this study was to investigate changes in health related quality of life (HRQOL) among HIV patients following switch from a first- to second-line antiretroviral therapy (ART) regimen. RESEARCH DESIGN AND METHODS: This was an observational study of adult HIV patients in the US at 35 academic and community health centers. Patients were required to be switching an antiretroviral regimen for the first time at the enrollment visit. Patients were assigned to a study cohort based on whether the switch was due to treatment related side effects or for any other reason as reported by their physician. Patients completed the Medical Outcomes Study-Human Immunodeficiency Virus (MOS HIV) health survey, the Depression, Anxiety, and Stress Scale Short Form (DASS 21), and the Human Immunodeficiency Virus Treatment Satisfaction Questionnaire status (HIVTSQs) at the enrollment visit (baseline) and a follow-up survey was completed approximately 4 weeks later. The within cohort change in survey measures from baseline to follow-up was assessed by two-sample paired t-test. RESULTS: Patients who switched their ART regimen due to treatment-related side effects (n = 50) had statistically significant improvements (p < .05, baseline to follow-up) in mean Physical and Mental Health Summary scores (MOS-HIV scale) and in all three HIVTSQ summary scores. Patients who switched for other reasons (n = 44) did not experience statistically significant improvements in these same measures. CONCLUSIONS: HIV patients whose regimen was switched due to treatment related side effects experienced an improvement in QOL following the switch. Physicians should take the potential impact on QOL into consideration when deciding on a switch in ART regimen, particularly when patients are intolerant of their current treatment. The results are based on a patient survey and may have been influenced by recall and response bias. PMID- 27552555 TI - Field-stepped broadband NMR in pulsed magnets and application to SrCu2(BO3)2 at 54T. AB - Pulsed magnets generate the highest magnetic fields as brief transients during which the observation of NMR is difficult, however, this is the only route to unique insight into material properties up to the regime of 100T. Here, it is shown how rather broad NMR spectra can be assembled in a pulsed magnet during a single field pulse by using the inherent time dependence of the field for the recording of field-stepped free induction decays that cover a broad frequency range. The technique is then applied to (11)B NMR of the spin-dimer system SrCu2(BO3)2, a magnetic insulator known to undergo a series of field-driven changes of the magnetic ground state. At peak fields of about 54T at the Dresden High Magnetic Field Laboratory, (11)B NMR spectra spanning a total of about 9MHz width are reconstructed. The results are in good accordance with a change from a high-temperature paramagnetic state to a low-temperature commensurate superstructure of field-induced spin-dimer triplets. PMID- 27552556 TI - A permanent MRI magnet for magic angle imaging having its field parallel to the poles. AB - A novel design of open permanent magnet is presented, in which the magnetic field is oriented parallel to the planes of its poles. The paper describes the methods whereby such a magnet can be designed with a field homogeneity suitable for Magnetic Resonance Imaging (MRI). Its primary purpose is to take advantage of the Magic Angle effect in MRI of human extremities, particularly the knee joint, by being capable of rotating the direction of the main magnetic field B0 about two orthogonal axes around a stationary subject and achieve all possible angulations. The magnet comprises a parallel pair of identical profiled arrays of permanent magnets backed by a flat steel yoke such that access in lateral directions is practical. The paper describes the detailed optimization procedure from a target 150mm DSV to the achievement of a measured uniform field over a 130mm DSV. Actual performance data of the manufactured magnet, including shimming and a sample image, is presented. The overall magnet system mounting mechanism is presented, including two orthogonal axes of rotation of the magnet about its isocentre. PMID- 27552557 TI - US-guided Microwave Ablation of Hyperplastic Parathyroid Glands: Safety and Efficacy in Patients with End-Stage Renal Disease-A Pilot Study. AB - Purpose To evaluate the safety and efficacy of microwave ablation (MWA) in patients with end-stage renal disease and secondary hyperparathyroidism. Materials and Methods The study protocol was approved by the human ethics review committee. Between March 1, 2014, and June 30, 2015, 51 patients (25 men, 26 women; mean age +/- standard deviation, 53.1 years +/- 12.9) were enrolled. All patients had at least one enlarged parathyroid gland and secondary symptomatic hyperparathyroidism, which was treated with ultrasonographically (US) guided MWA. The levels of intact parathyroid hormone, serum calcium, phosphorus, and alkaline phosphatase were compared before and after MWA. Paired-sample t tests and paired sample Wilcoxon signed-rank tests were used to compare treatment outcomes before and after MWA. Results Complete ablation was achieved in all 96 glands in 51 of 120 patients with severe secondary hyperparathyroidism. The mean follow-up time was 11.1 months +/- 3.3. The maximum diameter of the glands ranged from 0.5 cm to 4.8 cm (mean, 1.5 cm +/- 0.6). The ablation time for each gland was 216.1 seconds +/- 130.1. The mean serum intact parathyroid hormone, calcium, and phosphorus levels after MWA (400 pg/mL [400 ng/L; range, 151.3-629.0 ng/L], 2.33 mmol/L +/- 0.23, and 1.54 mmol/L +/- 0.43, respectively) were significantly lower than those before MWA (1203 pg/mL [1203 ng/L; range, 854.7-1694.5 ng/L], 2.53 mmol/L +/- 0.24, and 1.97 mmol/L +/- 0.50, respectively; P < .01), while the alkaline phosphatase levels did not change with MWA (P > .05). Ipsilateral recurrent laryngeal nerve injury was seen in one patient (2%). A hematoma developed during one procedure in one patient (2%) and was treated successfully with injection of thrombin. Conclusion US-guided MWA is safe and effective for destroying parathyroid gland tissue in patients with end-stage renal disease and severe secondary hyperparathyroidism. Further experience with the technique is clearly necessary. (c) RSNA, 2016. PMID- 27552558 TI - Colorectal Findings at Repeat CT Colonography Screening after Initial CT Colonography Screening Negative for Polyps Larger than 5 mm. AB - Purpose To determine the rate and types of polyps detected at repeat computed tomographic (CT) colonography screening after initial negative findings at CT colonography screening. Materials and Methods Among 5640 negative CT colonography screenings (no polyps >= 6 mm) performed before 2010 at one medical center, 1429 (25.3%; mean age, 61.4 years; 736 women, 693 men) patients have returned for repeat CT colonography screening (mean interval, 5.7 years +/- 0.9; range, 4.5 10.7 years). Positive rates and histologic findings of initial and repeat screening were compared in this HIPAA-compliant, institutional review board approved study. For all patients with positive findings at repeat CT colonography, the findings were directly compared against the initial CT colonography findings. Fisher exact, Pearson chi2, and Student t tests were applied as indicated. Results Repeat CT colonography screening was positive for lesions 6 mm or larger in 173 (12.1%) adults (compared with 14.3% at initial CT colonography screening, P = .29). In the 173 patients, 29.5% (61 of 207) of nondiminutive polyps could be identified as diminutive at the initial CT colonography and 12.6% (26 of 207) were missed. Large polyps, advanced neoplasia (advanced adenomas and cancer), and invasive cancer were seen in 3.8% (55 of 1429), 2.8% (40 of 1429), and 0.14% (two of 1429), respectively, at follow-up, compared with 5.2% (P = .02), 3.2% (P = .52), and 0.45% (P = .17), respectively, at initial screening. Of 42 advanced lesions in 40 follow-up screenings, 33 (78.6%) were right sided and 22 (52.4%) were flat, compared with 45.4% (P < .001) and 11.3% (P < .001), respectively, at initial screening. Large right-sided serrated lesions were confirmed in 20 individuals (1.4%), compared with 0.5% (P < .001) confirmed at initial screening. Conclusion Positive rates for large polyps at repeat CT colonography screening (3.7%) were lower compared with those at initial screening (5.2%). However, more advanced right-sided lesions were detected at follow-up CT colonography, many of which were flat, serrated lesions. The cumulative findings support both the nonreporting of diminutive lesions and a 5-10-year screening interval. (c) RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on August 30, 2016. PMID- 27552559 TI - Recent trends in metabolic engineering of microorganisms for the production of advanced biofuels. AB - As climate change has become one of the major global risks, our heavy dependence on petroleum-derived fuels has received much public attention. To solve such problems, production of sustainable fuels has been intensively studied over the past years. Thanks to recent advances in synthetic biology and metabolic engineering technologies, bio-based platforms for advanced biofuels production have been developed using various microorganisms. The strategies for production of advanced biofuels have converged upon four major metabolic routes: the 2 ketoacid pathway, the fatty acid synthesis (FAS) pathway, the isoprenoid pathway, and the reverse beta-oxidation pathway. Additionally, the polyketide synthesis pathway has recently been attracting interest as a promising alternative biofuel production route. In this article, recent trends in advanced biofuels production are reviewed by categorizing them into three types of advanced biofuels: alcohols, biodiesel and jet fuel, and gasoline. Focus is given on the strategies of employing synthetic biology and metabolic engineering for the development of microbial strains producing advanced fuels. Finally, the prospects for future advances needed to achieve much more efficient bio-based production of advanced biofuels are discussed, focusing on designing advanced biofuel production pathways coupled with screening, modifying, and creating novel enzymes. PMID- 27552560 TI - Surgeon's Responsibility for Patient Care-Reply. PMID- 27552561 TI - Both doctors and patients are victims in China. PMID- 27552562 TI - Tako-tsubo syndrome induced by a polidecanol injection: A case report. PMID- 27552563 TI - A rare cause of pericardial constriction. PMID- 27552564 TI - A randomized, placebo-controlled, double-blind study on the effects of (-) epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects. AB - BACKGROUND: Cardiometabolic disruptions such as insulin resistance, obesity, high blood pressure, hyperglycemia, and dyslipidemias, are known to increase the risk for cardiovascular and metabolic diseases such as type 2 diabetes mellitus and atherosclerosis. Several screening tools for assessing cardiometabolic risk have been developed including the TG/HDLc ratio, which has been, demonstrated to possess a strong association with insulin resistance and coronary disease. Dietary modifications, together with regular moderate exercise have proven to be effective in attenuating cardiometabolic disruptions. However, they often exhibit poor long-term patient compliance. Nutraceutics, including (-)-epicatechin (EPI), have gained increasing interest as coadjuvant effective and safe therapies that are able to attenuate hypertension, hyperglycemia, hyperinsulinemia, hypertriglyceridemia and hypoalphalipoproteinemia. METHODS: The aims of this study were: 1) to compare the in vitro effect of EPI vs. (+)-catechin on fructose induced triglyceride accumulation and mitochondrial function in Hep2 cells in culture, 2) to evaluate the efficacy of EPI treatment in reducing fasting blood triglycerides and improving the TG/HDLc ratio in hypertriglyceridemic patients with a total daily dose of 100mg of EPI. Secondary clinical variables included total cholesterol, LDLc, fructosamine, glucose, insulin, and high sensitivity C reactive protein blood levels. RESULTS AND CONCLUSION: Our results provide preliminary evidence as to favorable effects of EPI on glycemia homeostasis, lipid profile and systemic inflammation such bioactive actions are not class effects (i.e. limited to their antioxidant potential) but instead, may result from the specific activation of associated downstream signaling pathways since catechin has no effects. PMID- 27552565 TI - Biomarkers of cardiac injury in patients undergoing thoracic radiation therapy. PMID- 27552566 TI - Takotsubo cardiomyopathy and structural abnormalities of the left anterior descending coronary artery. PMID- 27552567 TI - Inappropriate shocks after implantable cardioverter-defibrillator for primary prevention in idiopathic cardiomyopathy: Independent determinants. PMID- 27552568 TI - Concomitant measurements of serum annexin A5 levels and hematological indices as markers in recent and old myocardial infarction with low ejection fraction: A preliminary study. AB - BACKGROUND: Serum annexin A5 (anxA5) level is significantly increased in patients with acute coronary syndrome. Hematological indices are significantly increased in patients with ischemic heart disease. This study aimed to demonstrate the changes in the distribution of blood cells and the levels of anxA5 in patients presented with significant low ejection fraction ST-elevation acute myocardial infarction (STEMI) in comparison with corresponding patients with ischemic heart disease. METHODS: Patients with low ejection fraction presenting at Hospital of Diyala University of Iraq were enrolled. Electrocardiograph (ECG), echocardiograph, hematological indices, serum annexin V (anxV) levels and the determinants of the cardio-metabolic risk factors were performed. Based on clinical examination, ECG findings and laboratory tests, patients were divided into healthy subjects (n=20); patients with acute MI (n=40) and with chronic MI (n=12). RESULTS: Acute MI has significant high levels of serum triglyceride, uric acid and high mean value of red cell distribution width (RDW) compared with healthy subjects and chronic MI. Platelet distribution width (PDW) is significantly reduced in patients of acute MI and chronic MI compared with healthy subjects, whereas the plateletcrit (PCT) is significantly higher in acute MI compared with healthy subjects. There is an insignificant difference between the means of serum anxA5 levels of acute MI (35.6+/-7.2ng/ml) and chronic MI (32.4+/-8.9ng/ml), but significantly higher than the cutoff level of the healthy subjects (5ng/ml). CONCLUSIONS: Measurement of serum annexin level is a useful diagnostic marker of acute or chronic MI with low ejection fraction. PMID- 27552569 TI - Reduced dose and reduced exposure to non-vitamin K-antagonist oral anticoagulants: Some considerations on this relationship. PMID- 27552570 TI - Takotsubo cardiomyopathy during electrophysiological study with isoproterenol. PMID- 27552571 TI - Caval penetration of IVC Filter caused neuralgia of celiac plexus 2years after implantation. PMID- 27552572 TI - Current bioresorbable scaffold technologies for treatment of coronary artery diseases: Do polymer and Magnesium platforms differ? PMID- 27552573 TI - Profiles of body mass index and the nutritional status among children and adolescents categorized by waist-to-height ratio cut-offs. AB - BACKGROUND: Waist-to-height ratio (WHtR) is proposed as a simple, valid and convenient measure of abdominal obesity and health risks in practice. The present study examined the distribution of nutritional status among children and adolescents categorized by WHtR cut-offs. METHODS: A total of 30,459 students (15,249 boys and 15,210 girls) aged 7-18years participated in the study. Height, weight and waist circumference (WC) of all subjects were measured, body mass index (BMI) and WHtR were calculated. The grades of nutritional status (thinness, normal weight, overweight and obesity) was defined by the international BMI cut offs. All subjects were divided into three groups (low, moderate and high) according to their WHtR, BMI level and the distribution of nutritional status among the three groups were compared. RESULTS: In both boys and girls, significant differences in BMI level and the nutritional status were observed among the three groups. Children and adolescents aged 7-18years in the 'high WHtR group' (>=0.5) had higher BMI than those in the 'low WHtR group' (<0.4) by 6.00 10.15kg/m2 for boys and 5.24-9.51kg/m2 for girls. 'low WHtR group' had higher prevalence of thinness, and 'high WHtR group' had higher prevalence of overweight and obesity. The optimal distribution of nutritional status is found in the 'moderate WHtR group' (between 0.4 and 0.5) with the highest proportion of normal weight and low prevalence of thinness and obesity. CONCLUSION: WHtR is associated with nutritional status, which could be an indicator of nutritional status and early health risk. It is necessary to develop optimal boundary values in the future. PMID- 27552574 TI - Sleep duration, sleep quality and coronary heart disease mortality. PMID- 27552575 TI - Double valve replacement of the mitral and tricuspid valves: An uncommon result of Austrian syndrome. PMID- 27552576 TI - Vein thrombosis after ECMO decannulation, a frequent and sometimes missed complication. PMID- 27552577 TI - Early repolarization and risk of arrhythmia events in long QT syndrome. PMID- 27552578 TI - Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: Real-world data from the GARFIELD-AF registry. AB - OBJECTIVE: To compare the distribution of international normalized ratios (INRs) in patients receiving vitamin K antagonist (VKA) for newly diagnosed atrial fibrillation in Eastern and Southeastern Asia and in other regions of the world (ORW) represented in the ongoing, global observational study GARFIELD-AF. METHODS AND RESULTS: 3621 and 13,541 patients were recruited prospectively in 2010-2013 from Asia and ORW, respectively. At baseline, excluding patients with unknown antithrombotic treatment, 1356 (37.8%) in Asia and 7081 (53.3%) in ORW received VKA (+/-antiplatelets). INR readings during 1-year follow-up were analyzed for VKA-treated patients with >=3 measurements (878 [64.7%] patients in Asia, 4452 [62.9%] in ORW). VKA-treated patients in Asia were younger than those in ORW (mean 67.1 vs 71.3years), with a lower CHA2DS2-VASc score (3.0 vs 3.5), but a similar HAS-BLED score (1.3 vs 1.4). Mean INR was lower in Asia than in ORW (2.0 vs 2.4). The proportion of time in the therapeutic range, defined using the multinational target of 2.0-3.0, was substantially lower in Asia (31.1% vs 54.1%). In Asia and ORW, 59.3% and 28.2% of INRs were <2, and 9.6% and 17.7% were >3, respectively. The same trend was found in different age groups (<65, 65-74, >=75years). CONCLUSION: GARFIELD-AF data demonstrate a difference in the distribution of INRs in patients from Asia versus other regions under current real-world practice. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362. PMID- 27552579 TI - Association between dietary protein intake and risk of stroke: A meta-analysis of prospective studies. PMID- 27552580 TI - Three-Dimensional Hierarchical Reduced Graphene Oxide/Tellurium Nanowires: A High Performance Freestanding Cathode for Li-Te Batteries. AB - Three-dimensional aerogel with ultrathin tellurium nanowires (TeNWs) wrapped homogeneously by reduced graphene oxide (rGO) is realized via a facile hydrothermal method. Featured with high conductivity and large flexibility, the rGO constructs a conductive three-dimensional (3D) backbone with rich porosity and leads to a free-standing, binder-free cathode for lithium-tellurium (Li-Te) batteries with excellent electrochemical performances. The cathode shows a high initial capacity of 2611 mAh cm(-3) at 0.2 C, a high retention of 88% after 200 cycles, and a high-rate capacity of 1083 mAh cm(-3) at 10 C. In particular, the 3D aerogel cathode delivers a capacity of 1685 mAh cm(-3) at 1 C after 500 cycles, showing pronounced long-cycle performance at high current density. The performances are attributed to the well-defined flexible 3D architecture with high porosity and conductivity network, which offers highly efficient channels for electron transfer and ionic diffusion while compromising volume expansion of Te in charge/discharge. Owing to such advantageous properties, the reported 3D rGO/tellurium nanowire (3DGT) aerogel presents promising application potentials as a high-performance cathode for Li-Te batteries. PMID- 27552581 TI - Longitudinal assessment of procedural skills. PMID- 27552582 TI - Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti Alzheimer Agents. AB - Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, 5r, IC50 = 0.204 MUM, SI > 196; 5t, IC50 = 0.067 MUM, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced Abeta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound 5r displayed appropriate blood-brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of scopolamine-induced amnesia mice. The multifunctional profiles of 5r and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease. PMID- 27552583 TI - Normal gait speed, grip strength and thirty seconds chair stand test among older Indians. AB - INTRODUCTION: Gait speed, maximum grip strength and thirty seconds chair stand test are quick, reliable measures of functional capacity in older adults. The objective of this study was to develop normative data of the said parameters, which is lacking in older Indians. METHODOLOGY: In a cross sectional study, 723 participants of >=60 years without any morbidity, were recruited with written consent at Geriatric Medicine clinic of All India Institute of Medical sciences, New Delhi. Time taken to walk comfortably (4m) was taken as Gait speed. Maximum grip strength was assessed by using dynamometer by pressing it for 3 times in each hand, and the best of six values noted. Thirty second chair stand was assessed by the number of repetitions to stand and sit from a chair in thirty second. RESULT: The Cut-off (25th percentile) of gait speed for both male and female in all age group was 0.6m/s. The Cut-off for maximum grip strength in 60 65 years, 66-70 years and >70 years for male were 20, 15 and 15 and for females were 8, 6 and 6 in kg, respectively. The Cut-off for thirty second chair stand test in 60-65 years, 66-70 years and >70 years for male were 10, 9 and 8 and for females was 8, 8 and 7, respectively. CONCLUSION: These normative data would be useful to the clinicians and researcher as Indian reference value, which is less as compared to western data. Community based multi-centre study is needed. PMID- 27552584 TI - The most cited articles in coronary heart disease: A bibliometric analysis between 1970 and 2015. AB - BACKGROUND: Research on coronary heart disease (CHD) remains one of the major concerns in the medical and health fields in recent decades, yet data on the circumstances of CHD are unsatisfying. We aimed to evaluate the situations and trends of the most cited articles in CHD via bibliometric approaches. METHODS AND RESULTS: The Web of Science database was used to identify the 100 most cited articles concerning CHD. General and bibliometric information was collected and analyzed. The total citations ranged from 7829 to 1157. Clinical trial was the largest proportion in article type while risk factor was the most preferred study content. The New England Journal of Medicine published the most T100 articles (n=31), followed by Lancet (n=21), Circulation (n=19) and JAMA (n=12). The USA and UK were the leading countries in the field of CHD, and contributed enormously in combating CHD. CONCLUSIONS: This study presented a detailed analysis of the 100 most cited articles focused on CHD in recent decades, which provides insights into the circumstances and trends in preventing and treating CHD. PMID- 27552585 TI - Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial. AB - Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ?21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ?21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID- 27552588 TI - Bifactor Analysis to Disentangle the Depression-Dementia Association. PMID- 27552587 TI - Bilateral ECT induces bilateral increases in regional cortical thickness. AB - Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT. PMID- 27552586 TI - Loss of promoter IV-driven BDNF expression impacts oscillatory activity during sleep, sensory information processing and fear regulation. AB - Posttraumatic stress disorder is characterized by hyperarousal, sensory processing impairments, sleep disturbances and altered fear regulation; phenotypes associated with changes in brain oscillatory activity. Molecules associated with activity-dependent plasticity, including brain-derived neurotrophic factor (BDNF), may regulate neural oscillations by controlling synaptic activity. BDNF synthesis includes production of multiple Bdnf transcripts, which contain distinct 5' noncoding exons. We assessed arousal, sensory processing, fear regulation and sleep in animals where BDNF expression from activity-dependent promoter IV is disrupted (Bdnf-e4 mice). Bdnf-e4 mice display sensory hyper-reactivity and impaired electrophysiological correlates of sensory information processing as measured by event-related potentials (ERP). Utilizing electroencephalogram, we identified a decrease in slow-wave activity during non-rapid eye movement sleep, suggesting impaired sleep homeostasis. Fear extinction is controlled by hippocampal-prefrontal cortical BDNF signaling, and neurophysiological communication patterns between the hippocampus (HPC) and medial prefrontal cortex (mPFC) correlate with behavioral performance during extinction. Impaired fear extinction in Bdnf-e4 mice is accompanied by increased HPC activation and decreased HPC-mPFC theta phase synchrony during early extinction, as well as increased mPFC activation during extinction recall. These results suggest that activity-dependent BDNF signaling is critical for regulating oscillatory activity, which may contribute to altered behavior. PMID- 27552590 TI - Use of vegetation sampling and analysis to detect a problem within a portion of a prairie restoration project. AB - In June 2005, the Department of Energy (DOE) began establishing the 60-ha Howell Prairie around the disposal cell at the DOE Weldon Spring Site (WSS). Prairies were historically present in the area of the site. Quantitative Cover sampling was used to quantify Total Cover, Native Grass Cover, Non-Native Grass Cover, Native Forb Cover, Non-Native Forb Cover, Warm Season (C4 Grass), Cool Season (C3 Grass), Perennial Cover and Annual Cover, Litter, and Bare Ground. Four permanent vegetation sampling plots were established. The first 4 years of vegetation measurements at Howell Prairie were made during above-average rainfall years on burned and unburned plots. The fifth-year (2012) vegetation measurements were made after below-average rainfall. Five years of results not only document the consistency of the restoration effort in three areas, but also demonstrate deficiencies in Grass Cover in a fourth area. The results are not only useful for Howell Prairie, but will be useful for restoration work throughout the region. Restoration work suffers from a lack of success monitoring and in this case from a lack of available reference areas. Floristic Quality Indices are used to make qualitative comparisons of the site to Konza Prairie sites. PMID- 27552591 TI - Reply to the Letter to the Editor, "Association between Exposure to Smartphones and Ocular Health in Adolescents". PMID- 27552589 TI - Emerging Applications of Therapeutic Ultrasound in Neuro-oncology: Moving Beyond Tumor Ablation. AB - : : Transcranial focused ultrasound (FUS) can noninvasively transmit acoustic energy with a high degree of accuracy and safety to targets and regions within the brain. Technological advances, including phased-array transducers and real time temperature monitoring with magnetic resonance thermometry, have created new opportunities for FUS research and clinical translation. Neuro-oncology, in particular, has become a major area of interest because FUS offers a multifaceted approach to the treatment of brain tumors. FUS has the potential to generate cytotoxicity within tumor tissue, both directly via thermal ablation and indirectly through radiosensitization and sonodynamic therapy; to enhance the delivery of therapeutic agents to brain tumors by transiently opening the blood brain barrier or improving distribution through the brain extracellular space; and to modulate the tumor microenvironment to generate an immune response. In this review, we describe each of these applications for FUS, the proposed mechanisms of action, and the preclinical and clinical studies that have set the foundation for using FUS in neuro-oncology. ABBREVIATIONS: BBB, blood-brain barrierCED, convection-enhanced delivery5-Ala, 5-aminolevulinic acidFUS, focused ultrasoundGBM, glioblastoma multiformeHSP, heat shock proteinMRgFUS, magnetic resonance-guided focused ultrasoundpFUS, pulsed focused ultrasound. PMID- 27552593 TI - Patterns of separation anxiety symptoms amongst pregnant women in conflict affected Timor-Leste: Associations with traumatic loss, family conflict, and intimate partner violence. AB - BACKGROUND: Adult separation anxiety (ASA) symptoms are prevalent amongst young women in low and middle-income countries and symptoms may be common in pregnancy. No studies have focused on defining distinctive patterns of ASA symptoms amongst pregnant women in these settings or possible associations with trauma exposure and ongoing stressors. METHODS: In a consecutive sample of 1672 women attending antenatal clinics in Dili, Timor-Leste (96% response), we assessed traumatic events of conflict, ongoing adversity, intimate partner violence (IPV), ASA, post traumatic stress disorder (PTSD) and severe psychological distress. Latent Class Analysis was used to identify classes of women based on their distinctive profiles of ASA symptoms, comparisons then being made with key covariates including trauma domains of conflict, intimate partner violence (IPV) and ongoing stressors. RESULTS: LCA yielded three classes, comprising a core ASA (4%), a limited ASA (25%) and a low symptom class (61%). The core ASA class reported exposure to multiple traumatic losses and IPV and showed a pattern of comorbidity with PTSD; the limited ASA class predominantly reported exposure to ongoing stressors and was comorbid with severe psychological distress; the low symptom class reported relatively low levels of exposure to trauma and stressors. LIMITATIONS: The study is cross-sectional, cautioning against inferring causal inferences. CONCLUSIONS: The core ASA group may be in need of immediate intervention given the high rate of exposure to IPV amongst this class. A larger number of women experiencing a limited array of non-specific ASA symptoms may need assistance to address the immediate stressors of pregnancy. PMID- 27552592 TI - Change in blood levels of eicosapentaenoic acid and posttraumatic stress symptom: A secondary analysis of data from a placebo-controlled trial of omega3 supplements. AB - BACKGROUND: Eicosapentaenoic acid (EPA) is suggested to be protective against posttraumatic stress disorder (PTSD) from two observational studies. We previously conducted a randomized controlled trial and found no effect of docosahexaenoic acid (DHA) for prevention of PTSD. This secondary analysis aimed to determine whether change in blood levels of EPA is associated with PTSD symptoms. METHODS: The percentages of EPA, DHA, and arachidonic acid (AA) were measured in erythrocyte membranes at baseline and posttreatment in 110 participants with severe physical injury who were randomly assigned to receive either a daily dose of 1,470mg DHA and 147mg EPA or of placebo for 12 weeks. Associations between change in erythrocyte fatty acid levels during the trial controlling for each baseline level and PTSD severity at 12 weeks were analyzed by treatment arm. RESULTS: In the omega3 supplements arm, changes in EPA+DHA (p=.023) and EPA (p=.001) as well as the EPA:AA ratio (p=.000) and EPA: DHA ratio (p=.013) were inversely correlated with PTSD severity. Change in AA was positively correlated with PTSD severity (p=.001). LIMITATION: This trial was conducted at a single-center in Japan and PTSD symptoms in most participants were not serious. CONCLUSIONS: Increased erythrocyte level of EPA during the trial was associated with low severity of PTSD symptoms in patients receiving omega3 supplements. PMID- 27552594 TI - Different coping strategies amongst individuals with grandiose and vulnerable narcissistic traits. AB - OBJECTIVE: This study explored the relationships between coping with stress responses and grandiose and vulnerable narcissist traits. METHOD: A community sample of 170 adults (113 female) participated in this study. A cross-sectional design was employed that utilized self-report measures of trait anxiety, social desirability, coping with stress responses, and pathological narcissism. RESULTS: Regression models indicated that both grandiose and vulnerable narcissism traits are significantly associated with, in opposing directions, behavioural disengagement responses to stress when controlling for trait anxiety and social desirability. Vulnerable narcissism traits were significantly associated with the use of denial as coping with stress response when controlling for the same factors. CONCLUSION: These findings provide further evidence of the discriminant validity of the Pathological Narcissism Inventory and inform our understanding of the differences that grandiose and vulnerable narcissistic traits have on coping. PMID- 27552595 TI - Risk for developing dementia among patients with posttraumatic stress disorder: A nationwide longitudinal study. AB - OBJECTIVES: Previous studies suggested a relationship between posttraumatic stress disorder (PTSD) in the specific population (i.e., war survivors and veterans) and subsequent dementia risk. However, whether patients with PTSD in the general population were at an increased risk for developing dementia in later life remained unclear. METHODS: The Cox regression analysis was performed using data from the Taiwan National Health Insurance Research Database. The study sample comprised 1750 patients diagnosed with PTSD between 2001 and 2009 and 7000 age-/sex-matched individuals without PTSD. Those who developed dementia during follow-up to the end of 2011 were identified. RESULTS: After adjusting for demographic data and medical and psychiatric comorbidities, PTSD was an independent risk factor for the risk for subsequent dementia (hazard ratio [HR]=4.37; 95% confidence interval [CI]: 2.53-7.55). There was a dose-dependent relationship between PTSD severity indicated by the frequency of psychiatric clinics visiting of PTSD (times per year) and the risk of subsequent dementia (<5: HR: 2.81, 95% CI: 1.50-5.29; 5-10: 6.90, 95% CI: 3.09-15.40;>10: HR: 18.13, 95% CI: 9.13-36.00). Furthermore, patients with depressive disorder and medical comorbidities, such as cerebrovascular diseases, diabetes mellitus, and head injuries, exhibited a higher risk for developing dementia. DISCUSSIONS: Our study suggested a significant dose-dependent association between PTSD and its severity and an increased risk of developing dementia later in life. The importance of mental care for trauma victims would increase in the coming century, and our findings broadened another era for the end result of a widely prevalent psychiatric disorder. PMID- 27552596 TI - Cryopreservation of whole bovine ovaries: comparisons of different thawing protocols. AB - OBJECTIVE: The aim of this study was to perform a comparative investigation of several different thawing protocols and to determine an appropriate protocol for thawing whole bovine frozen ovaries. STUDY DESIGN: Bovine ovaries were slowly frozen and then thawed by applying different protocols. Ultrastructural change, follicle viability, and the hormone levels of culture supernatant were measured. RESULTS: The percentage of morphologically normal primordial follicles and the hormone levels of culture supernatant in group D (two-step, thawing in water at 39 degrees C) were significantly higher than those in any other group. Moreover, the ultrastructural alteration of oocyte in group D (two-step, thawing in water at 39 degrees C) was slighter than those in any other group. CONCLUSIONS: The two step protocol involving short-term exposure to water at a moderately high temperature (39 degrees C) proved to be a suitable for thawing bovine whole ovaries. PMID- 27552597 TI - Importance of the PMMA viscoelastic rheology on the reduction of the leakage risk during osteoporotic bone augmentation: A numerical leakage model through a porous media. AB - Osteoporotic fractures poses one of the most problematic health issues that affects millions of people by weakening their bones (Osteoporosis). Polymethylmethacrylate (PMMA) cement is usually used to augment the bone and stabilize the fractures. Despite the benefit of using PMMA, it might cause a leakage where the cement undesirably access the surrounding tissues or vessels and lead to a serious complications. Consequently, it is important to study the leakage phenomenon and associated geometric and operation interactions. Although the experimental leakage models have been reported in many studies, a representative numerical leakage model is not exist. Therefore, the objectives of the present paper are to: (a) to develop and validate a representative numerical leakage model; and (b) to investigate numerically and analytically the importance of the rheological parameters (viscosity and relaxation time) on the cement flow to reduce the risk of leakage. ANSYS Polyflow was utilized to implement a 2D numerical leakage model to study the interaction of complex rheological parameters of the cement with the operational and geometrical structure of the representative porous media. In this model, the cement (represented by the upper convected Maxwell model) flows from the entrance (tip of an 8 gauge cannula) through a porous media with a leakage path (blood vessels) toward the output (Bottom side). The verified and validated numerical leakage model showed the importance of the elastic and viscous part of the cement to control the uniformity of the distributed cement and augmentation pressure, respectively. Moreover, increasing the flow rate can lead to reduce the risk of leakage since the elastic effect will increase. Geometrical parameters of the porous media has a minor effect on changing the elasticity and subsequently on the uniformity of the distributed cement. In conclusion, Cement rheological parameters are found to be the most influential parameters to reduce the risk of leakage by controlling the uniformity of the distributed cement and the augmentation pressure. PMID- 27552598 TI - Deformation and fracture of echinoderm collagen networks. AB - Collagen networks provide the main structural component of most tissues and represent an important ingredient for bio-mimetic materials for bio-medical applications. Here we study the mechanical properties of stiff collagen networks derived from three different echinoderms and show that they exhibit non-linear stiffening followed by brittle fracture. The disordered nature of the network leads to strong sample-to-sample fluctuations in elasticity and fracture strength. We perform numerical simulations of a three dimensional model for the deformation of a cross-linked elastic fibril network which is able to reproduce the macroscopic features of the experimental results and provide insights into the internal mechanics of stiff collagen networks. Our numerical model provides an avenue for the design of collagen membranes with tunable mechanical properties. PMID- 27552599 TI - Shear deformations of human articular cartilage: Certain mechanical anisotropies apparent at large but not small shear strains. AB - Articular cartilage has pronounced through-the-thickness heterogeneity in both ultrastructure and mechanical function. The tissue undergoes a combination of large deformations in vivo, where shear is critical in both failure and chondrocyte death. Yet the microstructure mechanical response of cartilage to multi-axial large shear deformations is unknown. We harvested a total of 42 cartilage specimens from seven matched locations across the lateral femoral condyles and patellofemoral grooves of six human male donors (30.2+/-8.8yrs old, M+/-SD). With each specimen we applied a range of quasi-static, multi-axial large (simple) shear displacements both parallel and perpendicular to the local split line direction (SLD). Shear stresses in cartilage specimens from the patellofemoral grooves were higher, and more energy was dissipated, at all applied strains under loading parallel to the local SLD versus perpendicular, while specimens from the lateral condyles were mechanically anisotropic only under larger strains of 20% and 25%. Cartilage also showed significant intra donor variability at larger shear strains but no significant inter-donor variability. Overall, shear strain-energy dissipation was almost constant at 5% applied shear strain and increased nonlinearly with increasing shear magnitude. Our results suggest that full understanding of cartilage mechanics requires large strain analyses to account for nonlinear, anisotropic and location-dependent effects not fully realized at small strains. PMID- 27552600 TI - In-situ synthesis of AgNPs in the natural/synthetic hybrid nanofibrous scaffolds: Fabrication, characterization and antimicrobial activities. AB - Silver nanoparticles embedded within a nanofibrous polymer matrix have significant attention in recent years as an antimicrobial wound dressing materials. Herein, we have fabricated a novel Ag-polyurethane-zein hybrid nanofibrous scaffold for wound dressing applications. AgNPs were synthesized in situ via reduction of silver nitrate in electrospinning solution. Varying mass composition of the components showed the pronounced effect on the morphology and physicochemical properties of the composite fibers. Field-Emission Scanning Electron Microscopy (FESEM) images revealed that PU and zein with mass ratio 2:1 produced the bead-free continuous and uniformly distributed nanofibers. Fourier transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD) and Thermogravimetric Analysis (TGA) confirmed the well interaction between component polymers. Compared to the pristine PU nanofibers, composite fibers showed enhanced tensile strength, young's modulus and surface wettability. The antibacterial capacity of the nanofibrous membrane was evaluated against gram positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacterial strains via a zone of inhibition test, and the results showed high antibacterial performance for Ag incorporated composite mat. Experimental results of cell viability assay and microscopic imaging revealed that as-fabricated scaffolds have an excellent ability for fibroblast cell adhesion, proliferation and growth. Overall, as-fabricated antibacterial natural/synthetic composite scaffold can be a promising substrate for repairing skin defects. PMID- 27552601 TI - Biochemical properties and evaluation of washing performance in commercial detergent compatibility of two collagenolytic serine peptidases secreted by Aspergillus fischeri and Penicillium citrinum. AB - Filamentous fungi secrete diverse peptidases with different biochemical properties, which is of considerable importance for application in various commercial sectors. In this study, we describe the isolation of two fungal species collected from the soil of decayed organic matter: Aspergillus fischeri and Penicillium citrinum. In a submerged bioprocess, we observed better peptidase production with the fungus P. citrinum, which reached a peak production at 168 h with 760 U/mL, in comparison with the fungus A. fischeri, which reached a peak production at 72 h with 460 U/mL. In both situations, the fermentative medium contained 0.5% crushed feathers as a source of nitrogen. On performing biochemical characterization, we detected two alkaline serine peptidases: The one secreted by P. citrinum had optimal activity at pH 7.0 and at 45 degrees C, while the one secreted by A. fischeri had optimal activity in pH 6.5-8 and at 55-60 degrees C. Metallic ions were effective in modulating these peptidases; in particular, Cu2+ promoted negative modulation of both peptidases. The peptidases were stable and functional under conditions of nonionic surfactants, temperatures up to 45 degrees C for 1 h, and incubation over a wide pH range. In addition, it was observed that both peptidases had the capacity to hydrolyze collagen and performed well in removing an egg protein stain when supplemented into a commercial powder detergent; this was especially true for the peptidase from P. citrinum. PMID- 27552604 TI - An Old Pond, a Frog Leaps in the Sound of Water: Stanton Macdonald-Wright. PMID- 27552613 TI - A PIECE OF MY MIND. Nondisclosure. PMID- 27552614 TI - Integrated Behavioral and Primary Care: What Is the Real Cost? PMID- 27552615 TI - Genetics and the Evaluation of the Febrile Child. PMID- 27552616 TI - Association of Integrated Team-Based Care With Health Care Quality, Utilization, and Cost. AB - IMPORTANCE: The value of integrated team delivery models is not firmly established. OBJECTIVE: To evaluate the association of receiving primary care in integrated team-based care (TBC) practices vs traditional practice management (TPM) practices (usual care) with patient outcomes, health care utilization, and costs. DESIGN: A retrospective, longitudinal, cohort study to assess the association of integrating physical and mental health over time in TBC practices with patient outcomes and costs. SETTING AND PARTICIPANTS: Adult patients (aged >=18 years) who received primary care at 113 unique Intermountain Healthcare Medical Group primary care practices from 2003 through 2005 and had yearly encounters with Intermountain Healthcare through 2013, including some patients who received care in both TBC and TPM practices. EXPOSURES: Receipt of primary care in TBC practices compared with TPM practices for patients treated in internal medicine, family practice, and geriatrics practices. MAIN OUTCOMES AND MEASURES: Outcomes included 7 quality measures, 6 health care utilization measures, payments to the delivery system, and program investment costs. RESULTS: During the study period (January 2010-December 2013), 113,452 unique patients (mean age, 56.1 years; women, 58.9%) accounted for 163,226 person-years of exposure in 27 TBC practices and 171,915 person-years in 75 TPM practices. Patients treated in TBC practices compared with those treated in TPM practices had higher rates of active depression screening (46.1% for TBC vs 24.1% for TPM; odds ratio [OR], 1.91 [95% CI, 1.75 to 2.08), adherence to a diabetes care bundle (24.6% for TBC vs 19.5% for TPM; OR, 1.26 [95% CI, 1.11 to 1.42]), and documentation of self-care plans (48.4% for TBC vs 8.7% for TPM; OR, 5.59 [95% CI, 4.27 to 7.33]), lower proportion of patients with controlled hypertension (<140/90 mm Hg) (85.0% for TBC vs 97.7% for TPM; OR, 0.87 [95% CI, 0.80 to 0.95]), and no significant differences in documentation of advanced directives (9.6% for TBC vs 9.9% for TPM; OR, 0.97 [95% CI, 0.91 to 1.03]). Per 100 person years, rates of health care utilization were lower for TBC patients compared with TPM patients for emergency department visits (18.1 for TBC vs 23.5 for TPM; incidence rate ratio [IRR], 0.77 [95% CI, 0.74 to 0.80]), hospital admissions (9.5 for TBC vs 10.6 for TPM; IRR, 0.89 [95% CI, 0.85 to 0.94]), ambulatory care sensitive visits and admissions (3.3 for TBC vs 4.3 for TPM; IRR, 0.77 [95% CI, 0.70 to 0.85]), and primary care physician encounters (232.8 for TBC vs 250.4 for TPM; IRR, 0.93 [95% CI, 0.92 to 0.94]), with no significant difference in visits to urgent care facilities (55.7 for TBC vs 56.2 for TPM; IRR, 0.99 [95% CI, 0.97 to 1.02]) and visits to specialty care physicians (213.5 for TBC vs 217.9 for TPM; IRR, 0.98 [95% CI, 0.97 to 0.99], P > .008). Payments to the delivery system were lower in the TBC group vs the TPM group ($3400.62 for TBC vs $3515.71 for TPM; beta, -$115.09 [95% CI, -$199.64 to -$30.54]) and were less than investment costs of the TBC program. CONCLUSIONS AND RELEVANCE: Among adults enrolled in an integrated health care system, receipt of primary care at TBC practices compared with TPM practices was associated with higher rates of some measures of quality of care, lower rates for some measures of acute care utilization, and lower actual payments received by the delivery system. PMID- 27552617 TI - Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children. AB - IMPORTANCE: Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others. OBJECTIVE: To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. DESIGN, SETTING, AND PARTICIPANTS: Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets. EXPOSURES: A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. MAIN OUTCOMES AND MEASURES: Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group. RESULTS: The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 100%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment. CONCLUSIONS AND RELEVANCE: This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings. PMID- 27552619 TI - The High Cost of Prescription Drugs in the United States: Origins and Prospects for Reform. AB - IMPORTANCE: The increasing cost of prescription drugs in the United States has become a source of concern for patients, prescribers, payers, and policy makers. OBJECTIVES: To review the origins and effects of high drug prices in the US market and to consider policy options that could contain the cost of prescription drugs. EVIDENCE: We reviewed the peer-reviewed medical and health policy literature from January 2005 to July 2016 for articles addressing the sources of drug prices in the United States, the justifications and consequences of high prices, and possible solutions. FINDINGS: Per capita prescription drug spending in the United States exceeds that in all other countries, largely driven by brand name drug prices that have been increasing in recent years at rates far beyond the consumer price index. In 2013, per capita spending on prescription drugs was $858 compared with an average of $400 for 19 other industrialized nations. In the United States, prescription medications now comprise an estimated 17% of overall personal health care services. The most important factor that allows manufacturers to set high drug prices is market exclusivity, protected by monopoly rights awarded upon Food and Drug Administration approval and by patents. The availability of generic drugs after this exclusivity period is the main means of reducing prices in the United States, but access to them may be delayed by numerous business and legal strategies. The primary counterweight against excessive pricing during market exclusivity is the negotiating power of the payer, which is currently constrained by several factors, including the requirement that most government drug payment plans cover nearly all products. Another key contributor to drug spending is physician prescribing choices when comparable alternatives are available at different costs. Although prices are often justified by the high cost of drug development, there is no evidence of an association between research and development costs and prices; rather, prescription drugs are priced in the United States primarily on the basis of what the market will bear. CONCLUSIONS AND RELEVANCE: High drug prices are the result of the approach the United States has taken to granting government-protected monopolies to drug manufacturers, combined with coverage requirements imposed on government-funded drug benefits. The most realistic short-term strategies to address high prices include enforcing more stringent requirements for the award and extension of exclusivity rights; enhancing competition by ensuring timely generic drug availability; providing greater opportunities for meaningful price negotiation by governmental payers; generating more evidence about comparative cost-effectiveness of therapeutic alternatives; and more effectively educating patients, prescribers, payers, and policy makers about these choices. PMID- 27552620 TI - Time in Therapeutic Range in Warfarin-Treated Patients: Is Very Good Good Enough? PMID- 27552621 TI - Antiviral Agents Added to Corticosteroids for Early Treatment of Adults With Acute Idiopathic Facial Nerve Paralysis (Bell Palsy). AB - CLINICAL QUESTION: Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy? BOTTOM LINE: Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias. PMID- 27552622 TI - Trends in Use and Outcomes of Women Undergoing Hysterectomy With Electric Power Morcellation. PMID- 27552623 TI - Quality Improvement Intervention and Mortality of Critically Ill Patients. PMID- 27552618 TI - Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger. AB - IMPORTANCE: Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach. OBJECTIVE: To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature >38 degrees C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type. EXPOSURE: RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections. MAIN OUTCOMES AND MEASURES: Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores. RESULTS: Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43). CONCLUSIONS AND RELEVANCE: In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice. PMID- 27552624 TI - Quality Improvement Intervention and Mortality of Critically Ill Patients--Reply. PMID- 27552625 TI - Relationships Between Income, Health Behaviors, and Life Expectancy. PMID- 27552626 TI - Relationships Between Income, Health Behaviors, and Life Expectancy--Reply. PMID- 27552627 TI - Online Intervention for Prevention of Major Depression. PMID- 27552628 TI - Online Intervention for Prevention of Major Depression--Reply. PMID- 27552629 TI - Association of Infection in Early Life and Risk of Developing Type 1 Diabetes. PMID- 27552630 TI - Association of Infection in Early Life and Risk of Developing Type 1 Diabetes. PMID- 27552631 TI - Association of Infection in Early Life and Risk of Developing Type 1 Diabetes- Reply. PMID- 27552633 TI - A Safe and Sane Fourth. PMID- 27552634 TI - JAMA PATIENT PAGE. Planning to Return Home After Surgery. PMID- 27552636 TI - Correction to: J Med Food 2015;18(9):950-959. PMID- 27552635 TI - Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update. AB - INTRODUCTION: The most recent advance concerning levothyroxine (L-T4) therapy is the development of novel oral formulations: the liquid preparation, and the soft gel capsule. Areas covered: This review evaluates the most recent clinical studies about these new formulations. The liquid formulation has been shown to overcome: the food and beverages intereference with L-T4 tablets absorption, caused by food or coffee at breakfast; malabsorption induced by the increased gastric pH, resulting from atrophic gastritis, or due to proton-pump inhibitors; and malabsorption after bariatric surgery. The use of liquid L-T4 has been studied also in pregnancy, newborns and infants, suggesting a better bioequivalence than tablets. Finally, liquid L-T4 is more active than tablets in the control of thyroid-stimulating hormone (TSH) in hypothyroid patients without malabsorption, drug interference, or gastric disorders, leading to a hypothesized higher absorption of liquid L-T4 also in these patients. Few studies have evaluated soft gel L-T4 with promising results in patients with malabsorption related to coffee or gastritis. Expert opinion: Liquid L-T4 (and soft gel capsules) are more active than the tablet L-T4 in the control of TSH in hypothyroid patients with gastric disorders, malabsorption, or drug interference, but also in patients without absorption disorders. PMID- 27552637 TI - The pain-depression dyad and the association with sleep dysfunction in chronic rhinosinusitis. AB - BACKGROUND: Depression, pain, and sleep disturbance is a symptom cluster often found in patients with chronic illness, exerting a large impact on quality of life (QOL). A wealth of literature exists demonstrating a significant association between depression, pain, and sleep dysfunction in other chronic diseases. This relationship has not been described in patients with chronic rhinosinusitis (CRS). METHODS: Sixty-eight adult patients with CRS were prospectively enrolled. Patients at risk for depression were identified using the Patient Health Questionnaire-2 (PHQ-2) using a cut-off score of >=1. Pain experience was measured using the Brief Pain Inventory Short Form (BPI-SF) and the Short Form McGill Pain Questionnaire (SF-MPQ). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Forty-seven patients were at risk for depression. Significant positive correlations were found between total PSQI scores and all pain measures (R = 0.38-0.61, p <= 0.05) and between total PSQI scores and PHQ-2 scores (R = 0.46, p < 0.05). For patients at risk for depression, significant, positive correlations were found between pain measures, the total PSQI score, and the 3 PSQI subdomains (sleep latency, sleep quality, and daytime dysfunction; R = 0.31-0.61, p < 0.05). The relationship between pain and sleep dysfunction scores was not seen in the absence of depression. CONCLUSION: Depression, pain, and sleep dysfunction are interrelated in patients with CRS. In the absence of depression, significant correlations between pain and sleep are not observed, suggesting that depression plays a key role in this interaction. Further research is needed to investigate the complex relationship between depression, pain, and sleep dysfunction in CRS. PMID- 27552640 TI - Self-Assembly of Colloidal Nanocrystals: From Intricate Structures to Functional Materials. AB - Chemical methods developed over the past two decades enable preparation of colloidal nanocrystals with uniform size and shape. These Brownian objects readily order into superlattices. Recently, the range of accessible inorganic cores and tunable surface chemistries dramatically increased, expanding the set of nanocrystal arrangements experimentally attainable. In this review, we discuss efforts to create next-generation materials via bottom-up organization of nanocrystals with preprogrammed functionality and self-assembly instructions. This process is often driven by both interparticle interactions and the influence of the assembly environment. The introduction provides the reader with a practical overview of nanocrystal synthesis, self-assembly, and superlattice characterization. We then summarize the theory of nanocrystal interactions and examine fundamental principles governing nanocrystal self-assembly from hard and soft particle perspectives borrowed from the comparatively established fields of micrometer colloids and block copolymer assembly. We outline the extensive catalog of superlattices prepared to date using hydrocarbon-capped nanocrystals with spherical, polyhedral, rod, plate, and branched inorganic core shapes, as well as those obtained by mixing combinations thereof. We also provide an overview of structural defects in nanocrystal superlattices. We then explore the unique possibilities offered by leveraging nontraditional surface chemistries and assembly environments to control superlattice structure and produce nonbulk assemblies. We end with a discussion of the unique optical, magnetic, electronic, and catalytic properties of ordered nanocrystal superlattices, and the coming advances required to make use of this new class of solids. PMID- 27552638 TI - Global occurrence and heterogeneity of the Roseobacter-clade species Ruegeria mobilis. AB - Tropodithietic acid (TDA)-producing Ruegeria mobilis strains of the Roseobacter clade have primarily been isolated from marine aquaculture and have probiotic potential due to inhibition of fish pathogens. We hypothesized that TDA producers with additional novel features are present in the oceanic environment. We isolated 42 TDA-producing R. mobilis strains during a global marine research cruise. While highly similar on the 16S ribosomal RNA gene level (99-100% identity), the strains separated into four sub-clusters in a multilocus sequence analysis. They were further differentiated to the strain level by average nucleotide identity using pairwise genome comparison. The four sub-clusters could not be associated with a specific environmental niche, however, correlated with the pattern of sub-typing using co-isolated phages, the number of prophages in the genomes and the distribution in ocean provinces. Major genomic differences within the sub-clusters include prophages and toxin-antitoxin systems. In general, the genome of R. mobilis revealed adaptation to a particle-associated life style and querying TARA ocean data confirmed that R. mobilis is more abundant in the particle-associated fraction than in the free-living fraction occurring in 40% and 6% of the samples, respectively. Our data and the TARA data, although lacking sufficient data from the polar regions, demonstrate that R. mobilis is a globally distributed marine bacterial species found primarily in the upper open oceans. It has preserved key phenotypic behaviors such as the production of TDA, but contains diverse sub-clusters, which could provide new capabilities for utilization in aquaculture. PMID- 27552641 TI - Removal of pharmaceuticals and personal care products (PPCPs) from wastewater: A review. AB - The pharmaceutical and personal care products (PPCPs) are emerging pollutants which might pose potential hazards to environment and health. These pollutants are becoming ubiquitous in the environments because they cannot be effectively removed by the conventional wastewater treatment plants due to their toxic and recalcitrant performance. The presence of PPCPs has received increasing attention in recent years, resulting in great concern on their occurrence, transformation, fate and risk in the environments. A variety of technologies, including physical, biological and chemical processes have been extensively investigated for the removal of PPCPs from wastewater. In this paper, the classes, functions and the representatives of the frequently detected PPCPs in aquatic environments were summarized. The analytic methods for PPCPs were briefly introduced. The removal efficiency of PPCPs by wastewater treatment plants was analyzed and discussed. The removal of PPCPs from wastewater by physical, chemical and biological processes was analyzed, compared and summarized. Finally, suggestions are made for future study of PPCPs. This review can provide an overview for the removal of PPCPs from wastewater. PMID- 27552642 TI - Measuring inequalities in immunization in Wales and the impact of interventions. AB - We reviewed uptake of childhood immunization in Wales by quintile of deprivation and found that uptake was significantly lower in residents in the most socio economically deprived areas compared with the least deprived. Differences were greater in older children. Services generally met best practice recommended by the National Institute for Health and Care Excellence; however, follow up of children who had not responded to invitations to attend routine immunization sessions needed more consistent implementation. Over a three year period to 2014 15 the difference in uptake between upper and lower quintiles at the fourth birthday reduced from 8.9% to 6.7%. PMID- 27552643 TI - Left ventricular hypertrophy is a predictor of cardiovascular events in elderly hypertensive patients: Hypertension in the Very Elderly Trial. AB - OBJECTIVE: We assessed the prognostic value of ECG left ventricular hypertrophy (LVH) using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH) or Cornell product (CP-LVH) criteria in 3043 hypertensive people aged 80 years and over enrolled in the Hypertension in the Very Elderly Trial. METHODS: Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, cardiovascular diseases, stroke and heart failure in participants with and without LVH at baseline. The mean follow-up was 2.1 years. RESULTS: LVH identified by CV-LVH or CP-LVH criteria was associated with a 1.6-1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (hazard ratio 2.38, 95% CI 1.16-4.86). In sex-specific analyses, CV-LVH (hazard ratio 1.94, 95% CI 1.06-3.55) and CP-LVH (hazard ratio 2.36, 95% CI 1.25 4.45) were associated with an increased risk of stroke in women and of heart failure in men, CV-LVH (hazard ratio 6.47, 95% CI 1.41-29.79) and CP-LVH (10.63, 95% CI 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with Sokolow-Lyon-LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality. CONCLUSION: Use of Cornell voltage and Cornell product criteria for LVH predicted the risk of cardiovascular disease and stroke. Only Cornell product was associated with an increased risk of heart failure. This was particularly the case in men. The identification of ECG LVH proved to be important in very elderly hypertensive people. PMID- 27552639 TI - Genomic composition and dynamics among Methanomicrobiales predict adaptation to contrasting environments. AB - Members of the order Methanomicrobiales are abundant, and sometimes dominant, hydrogenotrophic (H2-CO2 utilizing) methanoarchaea in a broad range of anoxic habitats. Despite their key roles in greenhouse gas emissions and waste conversion to methane, little is known about the physiological and genomic bases for their widespread distribution and abundance. In this study, we compared the genomes of nine diverse Methanomicrobiales strains, examined their pangenomes, reconstructed gene flow and identified genes putatively mediating their success across different habitats. Most strains slowly increased gene content whereas one, Methanocorpusculum labreanum, evidenced genome downsizing. Peat-dwelling Methanomicrobiales showed adaptations centered on improved transport of scarce inorganic nutrients and likely use H+ rather than Na+ transmembrane chemiosmotic gradients during energy conservation. In contrast, other Methanomicrobiales show the potential to concurrently use Na+ and H+ chemiosmotic gradients. Analyses also revealed that the Methanomicrobiales lack a canonical electron bifurcation system (MvhABGD) known to produce low potential electrons in other orders of hydrogenotrophic methanogens. Additional putative differences in anabolic metabolism suggest that the dynamics of interspecies electron transfer from Methanomicrobiales syntrophic partners can also differ considerably. Altogether, these findings suggest profound differences in electron trafficking in the Methanomicrobiales compared with other hydrogenotrophs, and warrant further functional evaluations. PMID- 27552644 TI - Accessing clinical services and retention in care following screening for hypertension and diabetes among Malawian adults: an urban/rural comparison. AB - OBJECTIVE: Interventions to impact on the burden of chronic noncommunicable diseases, such as hypertension and diabetes, include screening of asymptomatic adults, but little is known about the subsequent course of clinical care. We report on the uptake of referral for clinical assessment and retention in care, following a large urban/rural population screening program in Malawi. METHODS: Adult residents were screened for raised blood pressure and raised fasting blood glucose at a demographic surveillance site in rural Karonga District and in urban Area 25, Lilongwe with well supported chronic care clinics. Successful uptake was defined as presenting for clinical assessment within 6 weeks of referral, and nonattenders were followed at home. Logistic regression was used to examine association of uptake with demographic and clinical factors. Retention was assessed using survival analysis techniques. RESULTS: A total of 27 305 participants were screened for hypertension and diabetes between May 2013 and September 2015. Of these, 4075 (14.9%) were referred for suspected hypertension (3640), diabetes (172), or both (263). Among those referred, 2480 (60.9%), reported for clinical assessment. Factors associated with uptake of care included being female, rural residency, older age, unemployment, prior medication, and diabetes. Retention, for those enrolled in care following a formal clinical assessment, was associated with the final diagnosis following clinical assessment, rural residency, and older age. CONCLUSION: Screening for hypertension and diabetes identifies large numbers of individuals who need further clinical assessment, but strategies are needed to ensure better linkage and retention into care. PMID- 27552645 TI - Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation. AB - BACKGROUND: Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. METHOD: Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. RESULTS: Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 +/- 0.8 to 8.3 +/- 0.7 to 8.7 +/- 0.7% in younger and from 5.8 +/- 0.3 to 5.0 +/- 0.4 to 4.7 +/- 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 +/- 0.1 to 1.4 +/- 0.2 to 1.7 +/- 0.3 mg/l), whereas the high-CRP group did not (from 4.8 +/- 0.5 to 5.4 +/- 0.5 to 5.4 +/- 0.6 mg/l), P less than 0.001 for interaction. CONCLUSION: Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation. PMID- 27552646 TI - A pilot feasibility study of virtual patient simulation to enhance social work students' brief mental health assessment skills. AB - This study presents preliminary feasibility and acceptability data on the use of virtual patient (VP) simulations to develop brief assessment skills within an interdisciplinary care setting. Results support the acceptability of technology enhanced simulations and offer preliminary evidence for an association between engagement in VP practice simulations and improvements in diagnostic accuracy and clinical interviewing skills. Recommendations and next steps for research on technology-enhanced simulations within social work are discussed. PMID- 27552647 TI - High Proton Conductivity of Zinc Oxalate Coordination Polymers Mediated by a Hydrogen Bond with Pyridinium. AB - A novel metal-organic framework, (Hpy)2[Zn2(ox)3].nH2O (n = 0, 1), having a pyridinium cation, was newly synthesized, and the crystal structures were determined. The hydrated compound shows a high proton conductivity of 2.2 * 10( 3) S cm(-1) at 298 K and 98% relative humidity. Single crystal XRD analysis revealed a rotational displacement factor for the hydrated pyridinium ring and elongated water site that is thought to cause the high proton conductivity. PMID- 27552648 TI - Why is pancreatic adenocarcinoma not screened for earlier? PMID- 27552649 TI - Lost in transition: A review of the unmet need of patients with attention deficit/hyperactivity disorder transitioning to adulthood. AB - This review discusses the unmet needs of patients with attention deficit/hyperactivity disorder (ADHD) who are transitioning into adulthood. Although awareness and recognition of ADHD in children, adolescents, and adults have improved in recent years, there is often an interruption in management of the disorder when adolescent patients transition to adult health care services. This review has the following objectives: (1) to identify key issues patients with ADHD (with or without an early diagnosis) face during transition into adulthood; (2) to review the current clinical practice and country-specific approaches to the management of the transition into adulthood for patients with ADHD; (3) to discuss challenges facing clinicians and their patients when drug treatment for ADHD is initiated; (4) to review current ADHD guidelines on transition management in Hong Kong, Singapore, South Korea, Turkey, and Africa; and (5) to examine economic consequences associated with ADHD. The review suggests that the transition period to adult ADHD may be an underresearched and underserved area. The transition period plays an important role regarding how ADHD symptoms may be perceived and acted upon by adult psychiatrists. Further studies are needed to explore the characteristics of the transition period. If only a fraction of adolescents go on to have mental disorders during adulthood, especially ADHD, it is crucial to identify their characteristics to target appropriate interventions at the beginning of the course of illness. There continues to be low recognition of adult ADHD and a severe lack of medical services equipped to diagnose and care for patients with ADHD transitioning from child to adult services. PMID- 27552650 TI - Dehydrogenation of Formic Acid at Room Temperature: Boosting Palladium Nanoparticle Efficiency by Coupling with Pyridinic-Nitrogen-Doped Carbon. AB - The use of formic acid (FA) to produce molecular H2 is a promising means of efficient energy storage in a fuel-cell-based hydrogen economy. To date, there has been a lack of heterogeneous catalyst systems that are sufficiently active, selective, and stable for clean H2 production by FA decomposition at room temperature. For the first time, we report that flexible pyridinic-N-doped carbon hybrids as support materials can significantly boost the efficiency of palladium nanoparticle for H2 generation; this is due to prominent surface electronic modulation. Under mild conditions, the optimized engineered Pd/CN0.25 catalyst exhibited high performance in both FA dehydrogenation (achieving almost full conversion, and a turnover frequency of 5530 h(-1) at 25 degrees C) and the reversible process of CO2 hydrogenation into FA. This system can lead to a full carbon-neutral energy cycle. PMID- 27552652 TI - Sites Related to Crawford Williamson Long in Georgia. AB - BACKGROUND: Crawford Williamson Long (1815 to 1878) was the first to use ether as an inhaled anesthetic for surgical operations. By not publishing his discovery for 7 yr, his pioneering work was largely overshadowed by that of Horace Wells (1815 to 1848), Charles Thomas Jackson (1805 to 1880), and William Thomas Green Morton (1819 to 1868). As a result, sites commemorating Long's discovery are not offered the same recognition as those affiliated with Wells or Morton. METHODS: We highlight sites in Athens, Danielsville, and Jefferson, Georgia, that honor the first man to regularly use ether as an anesthetic agent. Extensive site visits, examination of museum artifacts, and genealogical research were used to obtain information being presented. RESULTS: Historic Oconee Hill Cemetery in Athens is where Long and members of his family are buried. Established in 1856, it is closely linked to the history of Athens and the University of Georgia (Athens, Georgia). The main site we describe is the Crawford W. Long Museum, located in Jefferson, Georgia, which opened to the public in 1957. It has undergone extensive renovations and holds an expansive collection of Long's family heirlooms and personal artifacts. In addition, it displays an impressive art collection, depicting Long, surgical procedures, members of Long's family, and homes associated with him. Visitors to the museum may also enjoy a walking audio tour that highlights the life of Long and his contribution to medicine. CONCLUSIONS: We provide information on sites and artifacts that honor Georgia's most celebrated physician. Much of this has not been published before, and it is our hope that Crawford Williamson Long's legacy receives the attention it richly deserves. PMID- 27552653 TI - Enhanced Thalamic Spillover Inhibition during Non-rapid-eye-movement Sleep Triggers an Electrocortical Signature of Anesthetic Hypnosis. AB - BACKGROUND: Alterations in thalamic gamma-aminobutyric acid-mediated signaling are thought to underlie the increased frontal alpha-beta frequency electrocortical activity that signals anesthetic-induced loss of consciousness with gamma-aminobutyric acid receptor type A (GABAAR)-targeting general anesthetics. The general anesthetic etomidate elicits phasic extrasynaptic GABAAR activation ("spillover" inhibition) at thalamocortical neurons in vitro. We hypothesize that this action of etomidate at the thalamus is sufficient to trigger an increase in frontal alpha-beta frequency electrocortical activity and that this effect of etomidate is fully recapitulated by enhanced thalamic spillover inhibition in vivo. METHODS: We recorded electrocortical activity and sleep-wake behavior in freely behaving wild-type (n = 33) and extrasynaptic delta subunit-containing GABAAR knockout mice (n = 9) during bilateral microperfusion of the thalamus with etomidate and/or other pharmacologic agents that influence GABAAR or T-type Ca channel activity. RESULTS: Microperfusion of etomidate into the thalamus elicited an increase in alpha-beta frequency electrocortical activity that occurred only during non-rapid-eye-movement (REM) sleep (11.0 +/- 11.8% and 16.0 +/- 14.2% greater 8 to 12- and 12 to 30-Hz power, respectively; mean +/- SD; both P < 0.031) and was not affected by blockade of thalamic T-type Ca channels. Etomidate at the thalamus also increased spindle-like oscillations during non-REM sleep (4.5 +/- 2.4 spindle per minute with etomidate vs. 3.2 +/- 1.7 at baseline; P = 0.002). These effects of etomidate were fully recapitulated by enhanced thalamic extrasynaptic GABAAR-mediated spillover inhibition. CONCLUSIONS: These findings identify how a prototypic GABAAR-targeting general anesthetic agent can elicit the characteristic brain wave pattern associated with anesthetic hypnosis when acting at the thalamus by promoting spillover inhibition and the necessity of a preexisting non-REM mode of activity in the thalamus to generate this effect. PMID- 27552654 TI - A cost analysis of remote monitoring in a heart failure program. AB - In this study, we examine the cost per outcomes of remote monitoring services in home health care. The methodology followed case matched design via retrospective chart reviews. Results of the chi-square test suggest that there were no significant associations between the intervention and hospital readmissions, chi2 = (1, n = 210, p-value = .71, phi = .71). An independent t-test compared group means of the number of skilled nursing visits and agency costs, p-value of .002 and .000, respectively, favoring the standard of care group. Based on this data set, the home care agency lost $153.46 for each hospital readmission in the intervention group. The cost of care complicated the agency's resources through an increase in nursing visits without offsetting the agency's investment into technology; the cost did not support remote monitoring as a financially viable option to the standard of care. PMID- 27552655 TI - Effects of the nuclear disaster on marine products in Fukushima: An update after five years. AB - Original data (134Cs and 137Cs, and sampling location) of marine products in Fukushima Prefecture monitored during 2011-2015 (n = 32,492) were analyzed to present an updated detailed description of radiocesium contamination after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident and to examine taxon/habitat-specific decreasing trends in different areas. Furthermore, marine species data presented by the Tokyo Electric Power Company (TEPCO) during 2012 2015 (n = 5458) were analyzed to evaluate the decreasing trends of 137Cs inside and outside (within a 20 km radius) of the FDNPP port. Monitoring results by Fukushima Prefecture show that percentages of samples higher than the Japanese regulatory limit of 100 Bq kg-1-wet (>RL%) were higher, whereas those below the detection limit (RL% and HCO + H2O2 and another hydroperoxyl radical 2HO2 -> H2O2 + O2 in the presence of one carbon dioxide molecule. Both covalently bonded intermediates and weak intermolecular complexes are identified and characterized. We found that reactions that involve covalent intermediates have substantially higher activation barriers and are not likely to play a role in hydrogen transfer kinetics. The van der Waals complexation with carbon dioxide does not affect hydrogen transfer from formaldehyde, but it lowers the barrier for hydroperoxyl self-reaction by nearly 3 kcal/mol. This indicates that CO2 environment is likely to have catalytic effect on HO2 self-reaction, which needs to be included in kinetic combustion mechanisms in supercritical CO2. PMID- 27552661 TI - The impact of negative treatment experiences on persistent refusal of antipsychotics. AB - AIMS: We investigate reasons for persistent medication refusal in schizophrenia spectrum disorders and test whether factors that speak for a rational decision, such as negative experiences with medication or low symptom distress predict medication refusal, even after taking differences in insight into account. METHOD: We included 45 participants with schizophrenia spectrum disorders, of which 20 had refused antipsychotic medication for at least three months and assessed reasons for taking or not taking medication, labeling condition as mental disorder ("insight"), experiences with the previous treatments, symptoms and symptom distress, positive and negative consequences and experiences of psychosis, causal beliefs, therapeutic relationships with previous clinicians and attitudes towards medication. RESULTS: Groups did not differ in symptom severity but medication refusers reported significantly less insight, less satisfaction with their most-recent psychiatrist and with previous medication, and more negative beliefs about harmful effects of medication. They also felt less informed about medication. After controlling for insight, the perceived helpfulness of the previous treating psychiatrist (OR=0.30, z=5.58, p=0.018) and of previous medication (OR=0.27, z=6.87, p=0.009) and feeling insufficiently informed about medication (OR=0.53, z=3. 85, p=0.050) significantly predicted medication discontinuation. CONCLUSIONS: Building rapport with patients with a different view of the nature of their condition and encouraging informed decisions on medication are likely to improve medication adherence. However, the findings also suggest that refusing medication after a phase of initial adherence is also the consequence of negative experiences with medication and could result from weighing the pros against the cons. PMID- 27552663 TI - Phytochemical profiling as a solution to palliate disinfectant limitations. AB - The indiscriminate use of biocides for general disinfection has contributed to the increased incidence of antimicrobial tolerant microorganisms. This study aims to assess the potential of seven phytochemicals (tyrosol, caffeic acid, ferulic acid, cinnamaldehyde, coumaric acid, cinnamic acid and eugenol) in the control of planktonic and sessile cells of Staphylococcus aureus and Escherichia coli. Cinnamaldehyde and eugenol showed antimicrobial properties, minimum inhibitory concentrations of 3-5 and 5-12 mM and minimum bactericidal concentrations of 10 12 and 10-14 mM against S. aureus and E. coli, respectively. Cinnamic acid was able to completely control adhered bacteria with effects comparable to peracetic acid and sodium hypochlorite and it was more effective than hydrogen peroxide (all at 10 mM). This phytochemical caused significant changes in bacterial membrane hydrophilicity. The observed effectiveness of phytochemicals makes them interesting alternatives and/or complementary products to commonly used biocidal products. Cinnamic acid is of particular interest for the control of sessile cells. PMID- 27552664 TI - Phototoxic target lipid model of single polycyclic aromatic hydrocarbons. AB - A phototoxic target lipid model (PTLM) is developed to predict phototoxicity of individual polycyclic aromatic hydrocarbons (PAHs) measured either as median lethal concentration (LC50) or median lethal time (LT50) for a 50% toxic response. The model is able to account for the differences in the physical/chemical properties of PAHs, test species sensitivities, and variations in light source characteristics, intensity, and length of exposure. The PTLM is based on the narcotic target lipid model (NTLM) of PAHs. Both models rely on the assumption that mortality occurs when the toxicant concentration in the target lipid of the organism reaches a threshold concentration. The PTLM is applied to observed LC50s and LT50s for 20 individual PAHs, 15 test species-including arthropods, fishes, amphibians, annelids, mollusks, and algae-exposed to simulated solar and various UV light sources, for exposure times varying from less than 1 h to 100 h, a total of 333 observations. The LC50 concentrations range from less than 0.1 ug/L to greater that 104 ug/L. The model has 2 fitting parameters that are constant and apply to all PAHs and organisms. The root mean square errors of prediction for log(LC50) and log(LT50) are 0.473 and 0.382, respectively. The results indicate that the PTLM can predict the phototoxicity of single PAHs over a wide range of exposure conditions and to organisms with a wide range of sensitivities. Environ Toxicol Chem 2017;36:926-937. (c) 2016 SETAC. PMID- 27552662 TI - The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N end Rule ligase POE/UBR4 in Drosophila. AB - RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus. Disruption of this pathway is widely observed in cancer and other pathologies. Consequently, considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation. While much information has been garnered on the steps leading up to the activation and inactivation of core pathway components, comparatively little is known on the mechanisms controlling their expression and turnover. We recently identified several factors that dictate Drosophila MAPK levels. Here, we describe the function of one of these, the deubiquitinase (DUB) USP47. We found that USP47 acts post-translationally to counteract a proteasome-mediated event that reduces MAPK half-life and thereby dampens signaling output. Using an RNAi-based genetic interaction screening strategy, we identified UBC6, POE/UBR4, and UFD4, respectively, as E2 and E3 enzymes that oppose USP47 activity. Further characterization of POE-associated factors uncovered KCMF1 as another key component modulating MAPK levels. Together, these results identify a novel protein degradation module that governs MAPK levels. Given the role of UBR4 as an N-recognin ubiquitin ligase, our findings suggest that RAS-MAPK signaling in Drosophila is controlled by the N-end rule pathway and that USP47 counteracts its activity. PMID- 27552665 TI - Incentives for role models: Our most invaluable resource. PMID- 27552666 TI - Improvement of erythema dyschromicum perstans using a combination of the 1,550-nm erbium-doped fractionated laser and topical tacrolimus ointment. AB - BACKGROUND AND OBJECTIVE: Erythema dyschromicum perstans (EDP) is a cosmetically distressing, acquired pigmentary disorder of unknown etiology for which few successful therapies exist. Herein, we present the successful use of non-ablative fractional photothermolysis in combination with topical tacrolimus ointment. STUDY DESIGN/PATIENTS AND METHODS: A 35-year-old female with biopsy-confirmed EDP underwent a series of fractionated non-ablative treatment sessions utilizing the 1,550 nm erbium-doped fiber laser in combination with topical tacrolimus ointment over a period of 5 months. RESULTS: The patient's EDP improved by greater than 75% and results were maintained at the 8-month follow-up visit. CONCLUSION: The combination of non-ablative fractional photothermolysis and topical tacrolimus ointment is a potential safe and effective therapeutic option for erythema dyschromicum perstans. Additional prospective, comparative studies are warranted. Lasers Surg. Med. 49:60-62, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27552667 TI - Glucagon-Like Peptide-1 Receptor Agonists and Diabetic Cardiovascular Disease: Implications of the LEADER Study. PMID- 27552668 TI - Abnormal vascular and neural retinal morphology in congenital lifetime isolated growth hormone deficiency. AB - OBJECTIVE: Experimental models demonstrate an important role of GH in retinal development. However, the interactions between GH and the neuro-vascularization of the human retina are still not clear. A model of untreated congenital isolated GH deficiency (IGHD) may clarify the actions of GH on the retina. The purpose of this work was to assess the retinal neuro-vascularization in untreated congenital IGHD (cIGHD). DESIGN: In a cross sectional study, we performed an endocrine and ophthalmological assessment of 25 adult cIGHD subjects, homozygous for a null mutation (c.57+1G>A) in the GHRH receptor gene and 28 matched controls. Intraocular pressure measurement, retinography (to assess the number of retinal vascular branching points and the optic disc and cup size), and optical coherence tomography (to assess the thickness of macula) were performed. RESULTS: cIGHD subjects presented a more significant reduction of vascular branching points in comparison to controls (91% vs. 53% [p=0.049]). The percentage of moderate reduction was higher in cIGHD than in controls (p=0.01). The percentage of individuals with increased optic disc was higher in cIGHD subjects in comparison to controls (92.9% vs. 57.1%). The same occurred for cup size (92.9% vs. 66.7%), p<0.0001 in both cases. There was no difference in macula thickness. CONCLUSIONS: Most cIGHD individuals present moderate reduction of vascular branching points, increase of optic disc and cup size, but have similar thickness of the macula. PMID- 27552669 TI - Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys. AB - PURPOSE: TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys. METHOD: Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study. Serum levels of TV-1106 and insulin-like growth factor 1 (IGF-1) were assayed. RESULTS: Treated animals showed no adverse effects or histopathological changes. TV-1106 serum concentrations showed sustained exposure to the drug. Exposure increased in a dose-dependent manner with peak concentrations at approximately 24h post-dosing and elimination half-lives in the range of 12 to 24h. IGF-1 serum concentrations were elevated throughout the entire study duration, indicative of the pharmacological response. There was a clear correlation between change in IGF-1 levels and dose or exposure to TV-1106. CONCLUSIONS: The safety, pharmacokinetic and pharmacodynamic findings support the further development of TV-1106 as a once weekly administered treatment for patients with GHD. PMID- 27552670 TI - miR-181b-5p, miR-195-5p and miR-301a-3p are related with treatment resistance in schizophrenia. AB - The aim of the study was to determine the differences between expression levels of certain miRNAs, as their association with schizophrenia has been well presented in the literature, and to investigate their relation to treatment resistance in schizophrenic patients. Three groups were formed: 1) treatment resistant group, 2) treatment responsive group and 3) healthy control group. Expression levels of miRNAs from peripheric blood samples were determined by real time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We investigated the roles of 29 schizophrenia-related miRNAs in schizophrenia treatment and their potentials to be considered as indicators. Among these miRNAs, only miR-181b-5p, miR-195-5p and miR-301a-3p expressions were found to be significantly different between the treatment-resistant group and the group responding well to the treatment. miRNAs may cause resistance by silencing the receptor genes of the drugs used for schizophrenia treatment. miR-181b-5p, miR 195-5p and miR-301a-3p may be candidate indicators that can be used to reveal resistance against schizophrenia treatment. PMID- 27552671 TI - Appraisals of and recommendations for managing intrusive thoughts: An empirical investigation. AB - The present study investigated strategies for managing intrusive thoughts. Eighty undergraduate students read vignettes of intrusive thoughts - blasphemous, sexual, and violent - which varied in frequency of the thought (high or low) and who experienced the thought (self or other). Appraisal ratings of thoughts were completed and participants completed a response strategy survey where they indicated how much they would endorse various methods for dealing with the thoughts. Some response strategies were theorized to help with intrusive thoughts and some were theorized to be unhelpful. Measures of obsessive-compulsive tendencies were completed to determine relationships between beliefs and appraisals as well as responses to the intrusive thoughts. Results indicated the more distressing a thought was perceived to be, the more likely participants were to recommend unhelpful strategies. Conversely, the less distressing the thought was, the more likely participants were to recommend helpful strategies. Ratings of distress and patterns of responses were related to obsessive-compulsive beliefs as well. Findings are discussed in terms of their relationship to the cognitive behavioral model of OCD, intrusive thoughts, and how future work may serve to educate and reduce stigma related to these common yet distressing experiences. PMID- 27552672 TI - A longitudinal event-related potential study of selective serotonin reuptake inhibitor therapy in treatment-naive pediatric obsessive compulsive disorder patients. AB - Obsessive-compulsive disorder (OCD) is characterized by obsessive thoughts and/or compulsive behaviors, involving specific cognition and/or information processing disorders. Event-related potentials (ERPs) are commonly used as physiological measures of cognitive function. In conscious patients, ERPs are easily and non invasively measured. Previous ERP studies have revealed differences between OCD patients and control subjects. Whether ERPs reflect the pharmacological effects of OCD treatment, particularly in treatment-naive pediatric patients, remains unknown. We used the Child's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) to evaluate the symptomatic severity of 12 treatment-naive pediatric OCD patients. Comparisons were made with 12 age-, sex-, and intelligence-matched controls. The P300 and mismatch negativity (MMN) components were measured during an auditory odd-ball task at baseline in both groups and after the 3-year serotonin reuptake inhibitor (SSRI) treatment in OCD patients. Compared with controls, P300 amplitudes were smaller n the OCD group at Fz, Cz, Pz, C3, and C4. After SSRI treatment, P300 amplitudes increased partly at Fz and C4 in association with symptomatic improvements. We found a significant positive correlation between P300 amplitude in C4 and CY-BOCS scores. Our findings confirm the utility of SSRIs in pediatric OCD, and suggest the utility of ERPs for evaluating pharmacological effects in treatment-naive pediatric OCD patients. PMID- 27552673 TI - Sex and age trends in Australia's suicide rate over the last decade: Something is still seriously wrong with men in middle and late life. AB - Despite significant investment in mental health and suicide intervention strategies in Australia, the extent of change in suicide rates over the last decade is unclear. This paper analyses sex and age trajectories in suicide rates over the last decade in Australia. Age Standardized Suicide Rates from 2004 to 2013 were obtained from the Australian Bureau of Statistics and reflect rates of suicide per 100,000 within age and sex cohorts. Age-related suicide rates were consistent over the last decade. For both males and females, there were increases in mid-life suicide rates before declining around 55-65 years of age. However, rates of suicide in men increased in late-life with rates for those aged 70-79 comparable with those in mid-life. Rates amongst men aged 85+ were consistently the highest rates over the decade. Positively, there was decline in suicide rates among younger men aged 20-34 years. However, more consistently, for both sexes across most age cohorts, there were either increases or no change in suicide rate. Apart from declines in younger-adult males, analysis of age-standardized suicide rates indicate no improvement in suicide rates. High suicide rates amongst middle-aged and older males remain a significant public health issue that needs to be addressed. PMID- 27552674 TI - Radiative and Nonradiative Recombination in CuInS2 Nanocrystals and CuInS2-Based Core/Shell Nanocrystals. AB - Luminescent copper indium sulfide (CIS) nanocrystals are a potential solution to the toxicity issues associated with Cd- and Pb-based nanocrystals. However, the development of high-quality CIS nanocrystals has been complicated by insufficient knowledge of the electronic structure and of the factors that lead to luminescence quenching. Here we investigate the exciton decay pathways in CIS nanocrystals using time-resolved photoluminescence and transient absorption spectroscopy. Core-only CIS nanocrystals with low quantum yield are compared to core/shell nanocrystals (CIS/ZnS and CIS/CdS) with higher quantum yield. Our measurements support the model of photoluminescence by radiative recombination of a conduction band electron with a localized hole. Moreover, we find that photoluminescence quenching in low-quantum-yield nanocrystals involves initially uncoupled decay pathways for the electron and hole. The electron decay pathway determines whether the exciton recombines radiatively or nonradiatively. The development of high-quality CIS nanocrystals should therefore focus on the elimination of electron traps. PMID- 27552675 TI - Predictors of HbA1c levels in patients initiating metformin. AB - OBJECTIVE: The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. RESEARCH DESIGN AND METHODS: We conducted a cohort study including type 2 diabetes patients who received their first metformin prescription between 2007 and 2013 in the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was HbA1c level at follow-up adjusted for baseline HbA1c; the secondary outcome was failing to achieve the target HbA1c level of 53 mmol/mol. Associations were analyzed by linear and logistic regression. Multiple imputation was used for missing data. Additional analyses stratified by dose and adherence level were conducted. RESULTS: The cohort included 6050 patients initiating metformin. Baseline HbA1c at target consistently predicted better HbA1c outcomes. Longer diabetes duration and lower total cholesterol level at baseline were predictors for higher HbA1c levels at 6 months. At 18 months, cholesterol level was not a predictor. Longer diabetes duration was also associated with not achieving the target HbA1c at follow-up. The association for longer diabetes duration was especially seen in patients starting on low dose treatment. No consistent associations were found for comorbidity and comedication. CONCLUSIONS: Diabetes duration was a relevant predictor of HbA1c levels after 6 and 18 months of follow up in patients initiating metformin treatment. Given the study design, no causal inference can be made. Our study suggests that prompt treatment intensification may be needed in patients who have a longer diabetes duration at treatment initiation. PMID- 27552677 TI - Potential drug-drug interaction in Mexican patients with schizophrenia. AB - OBJECTIVE: The aim of this study was to observe potential drug-drug interactions in the medication of Mexican schizophrenic patients. METHODS: We performed a retrospective and cross-sectional study that was carried out in a psychiatric clinic. Only the prescriptions of patients with schizophrenia whose diagnoses were based on the DSM-IV instrument were included in this study. The Drug Interactions Checker software ( http://www.drugs.com/drug_interactions.html ) was used in this study to analyse potential drug-drug interactions. RESULTS: In total, 86 of 126 patients were at risk of potential drug-drug interactions. Haloperidol and biperiden was the most common drug pair of 232 pairs evaluated. In our study, 13.8% of drug-drug interaction showed a major level of severity, whereas in 83.2%, the interaction was moderate. Finally, central nervous system (CNS) depression and anticholinergic effect were the main possible effects of drug-drug interaction. CONCLUSIONS: Our results revealed a high number of patients with schizophrenia receiving two or more drugs. The potential drug-drug interactions observed in the Mexican population are consistent with the concomitant use of antipsychotics, benzodiazepines, and antidepressants prescribed in schizophrenia that could cause central nervous system (CNS) depression and anticholinergic effect. Drug-drug interaction must be considered when the patient with schizophrenia is medicated. PMID- 27552678 TI - Potential use of organogels to replace animal fat in comminuted meat products. AB - The replacement of beef fat (BF) with regular or structured canola oil [organogel produced with ethylcellulose (EC) 0.0%, 1.5% or 3.0% sorbitan monostearate (SMS)] was conducted in frankfurters. Substitution with regular oil doubled the hardness of the frankfurters relative to BF. Using an organogel prepared with 8% EC and 1.5 or 3.0% SMS resulted in a hardness value similar to that of BF, by both sensory and texture profile analysis. Without SMS addition, sensory results showed (P<0.05) lower hardness values than regular oil but still higher than BF. Gels prepared using higher EC concentrations (12 and 14%) yielded meat products with a higher sensory hardness than BF (P<0.05). Liquid oil based frankfurters had very small fat globules compared to BF, but structuring the oil yielded larger fat globules. Color measurements indicated that oil-containing frankfurters were lighter than the ones with BF. Smokehouse yields were generally higher for canola oil and organogel containing treatments compared to the beef fat treatment. When SMS was included, fat losses increased over the canola oil treatment. The results demonstrate the possibility to use organogels to replace beef fat and depending on the formulation to manipulate textural properties to resemble traditional products but with lower saturated fat content. PMID- 27552676 TI - Obesity and Airway Dysanapsis in Children with and without Asthma. AB - RATIONALE: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids. OBJECTIVES: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity. METHODS: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma. Adjusted odds ratios (ORs) were calculated for each cohort and in a combined analysis of all cohorts; longitudinal analyses were also performed for cohorts with available data. Hazard ratios (HRs) for clinical outcomes were calculated for children with asthma in the Childhood Asthma Management Program. MEASUREMENTS AND MAIN RESULTS: Being overweight or obese was associated with dysanapsis in both the cross-sectional (OR, 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and the longitudinal (OR, 4.31; 95% CI, 2.99-6.22 [for children who were overweight/obese at all visits compared with normal weight children]) analyses. Dysanapsis was associated with greater lung volumes (FVC, vital capacity, and total lung capacity) and lesser flows (FEV1 and forced expiratory flow, midexpiratory phase), and with indicators of ventilation inhomogeneity and anisotropic lung and airway growth. Among overweight/obese children with asthma, dysanapsis was associated with severe disease exacerbations (HR, 1.95; 95% CI, 1.38-2.75) and use of systemic steroids (HR, 3.22; 95% CI, 2.02-5.14). CONCLUSIONS: Obesity is associated with airway dysanapsis in children. Dysanapsis is associated with increased morbidity among obese children with asthma and may partly explain their reduced response to inhaled corticosteroids. PMID- 27552681 TI - Expanding the Health Care Response to Mass Violence. PMID- 27552679 TI - Cepheid xpert monitor platform for the confirmation of BCR-ABL1 IS conversion factors for the molecular monitoring of chronic myeloid leukaemia. AB - Molecular monitoring of BCR-ABL1 expression in chronic myeloid leukaemia (CML) is well established. As the International Scale (IS) normalised BCR-ABL1/ABL1 ratio at 3 months post-treatment is now an important milestone in patients' treatment schedule, the reliable and reproducible measurement of BCR-ABL1 levels is therefore paramount. IS conversion factors (CF) are established via sample exchange and yearly ratification with an external reference laboratory. Since any change to an established IS CF could lead to discontinuity in longitudinal results, we wished to add an internal verification step as an additional safeguard. We used the Cepheid GeneXpert qPCR and IS calibrated Xpert BCR-ABL Monitor cartridge system, parallel to our in-house pipeline on 50 CML samples, over the period of one week to verify the CF for those samples and compare it to the externally provided CF. The median non-IS in-house BCR-ABL1/ABL1 values were significantly different than that from the IS GeneXpert, but they became non significant when adjusted to CF provided by the CXM and by the current external CF, validating it. These metrics can help decide to accept or reject an updated CF value, especially where a significant change in CF might lead to a discontinuity in ongoing patient monitoring. PMID- 27552680 TI - Bone marrow B lymphocytes in multiple myeloma and MGUS: Focus on distribution of naive cells and memory subsets. AB - BACKGROUND/AIMS: Multiple myeloma (MM) is caused by proliferation of clonal plasma cells (cPCs) in bone marrow (BM), associated with numerical and functional defects in immune subsets. An impairment of B cell compartment is involved in onset/progression of the disease. METHODS: By flow cytometry, we studied distribution of naive/transitional (IgD(+)CD27(-)), memory unswitched (IgD(+)CD27(+)), memory switched (IgD(-)CD27(+)) and double negative (DN) (IgD( )CD27(-)) B lymphocytes in BM of control subjects, and responding and relapsing patients. RESULTS: We observed an increased percentage of IgD(+)CD27(+) B cells in healthy controls vs responding patients (p<0.05). Treated non complete responders exhibited an expanded DN compartment vs stringent complete responders (p=0.011); in turn IgD(+)CD27(-) subpopulation was larger in stringent complete responders vs other responding patients (p=0.006). None of the studied B cell subsets showed clonal restriction. Correlation analysis revealed negative correlations between naive/transitional and DN B cells in all groups, except in newly diagnosed subjects. CONCLUSIONS: This may be considered a feasible start point to explore the importance of B cells in the immunosuppressive MM BM microenvironment, correlating these findings with immunosenescence and therapy related increased risk of infection. Moreover, we propose a possible role of naive/transitional and DN B cells as predictive markers in treated patients. PMID- 27552683 TI - Diagnosing and treating respiratory syncytial virus bronchiolitis. AB - Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract illness in children and can lead to significant infection and death. This article discusses the incidence, clinical presentation, diagnosis, current treatment, and prevention options to successfully diagnose and treat infections caused by RSV. PMID- 27552682 TI - Phytochemical and Cytogenetic Characterization of Centaurea solstitialis L. (Asteraceae) from Croatia. AB - The cytogenetic characterization of Centaurea solstitialis L. (Asteraceae) showed a chromosome number of 2n = 16. Karyotype is composed by four pairs of metacentric, two pairs of submetacentric and two pairs of subtelocentric chromosomes. Physical mapping of two rDNA probes revealed two loci of 35S and one locus of 5S rRNA genes. Chromomycin fluorochrome banding revealed that all rDNA loci were GC rich. The genome size (2C-value) of 1.95 pg classes this species in the group of very small genomes. Chemical composition of C. solstitialis volatile oil (VO) from Croatia, studied with gas chromatography-mass spectrometry showed dominant components as it follows: hexadecanoic acid, alpha-linolenic acid, germacrene D and heptacosane. Antioxidant capacity, measured by ferric reducing power assay and 2,2-diphenyl-1-picrylhydrazyl methods, as well as inhibition of acetyl- and butyrylcholinesterase of VO was lower comparing to a standard solutions. Volatile oil tested with disc diffusion method showed good inhibitory potential against Pseudomonas aeruginosa, Escherichia coli and all tested fungi: Candida albicans, Penicillium funiculosum and Aspergillus fumigatus. The microdilution method showed best activity against Chronobacter sakazakii and A. fumigatus. PMID- 27552684 TI - Tuberculosis screening: An update for NPs. AB - One-third of the world's population is infected with Mycobacterium tuberculosis. If NPs are to effectively participate in eliminating and preventing tuberculosis (TB), they must be cognizant of the current CDC-approved TB screening methods and guidelines. PMID- 27552685 TI - Aggressive angiomyxoma. PMID- 27552686 TI - Cervical cancer: Screening, management, and prevention. PMID- 27552687 TI - Improving end-of-life care: Recommendations from the IOM. AB - A 2014 consensus report by the Institute of Medicine offers recommendations for healthcare providers to decrease unwanted care and improve the quality of life at the end of life. This article discusses the recommendations of interest to advanced practice registered nurses. PMID- 27552688 TI - Improving end-of-life care: Recommendations from the IOM. PMID- 27552689 TI - Fibromyalgia: Timely diagnosis and treatment options. AB - Fibromyalgia can be challenging to diagnose and treat, and patients often feel isolated and misunderstood. Surveys of patients with fibromyalgia suggest that patients would benefit from greater understanding and acceptance. NPs can provide this support and play a prominent role in helping patients manage their fibromyalgia. PMID- 27552690 TI - Eating disorders in men. AB - Eating disorders are traditionally thought of as a problem specific to women, but evidence suggests the disorders also occur in men. Identifying the problem and referring patients for treatment can be difficult. Understanding the nuances of these disorders and realizing the incidence in men is important, as it is often overlooked as a differential diagnosis. PMID- 27552692 TI - Cell type determination and association with the DNA donor. AB - In forensic casework, evidence regarding the type of cell material contained in a stain can be crucial in determining what happened. For example, a DNA match in a sexual offense can become substantially more incriminating when there is evidence supporting that semen cells are present. Besides the question which cell types are present in a sample, also the question who donated what (association) is very relevant. This question is surprisingly difficult, even for stains with a single donor. The evidential value of a DNA profile needs to be combined with knowledge regarding the specificity and sensitivity of cell type tests. This, together with prior probabilities for the different donor-cell type combinations, determines the most likely combination. We present a Bayesian network that can assist in associating donors and cell types. A literature overview on the sensitivity and specificity of three cell type tests (PSA test for seminal fluid, RSID saliva and RSID semen) is helpful in assigning conditional probabilities. The Bayesian network is linked with a software package for interpreting mixed DNA profiles. This allows for a sensitivity analysis that shows to what extent the conclusion depends on the quantity of available research data. This can aid in making decisions regarding further research. It is shown that the common assumption that an individual (e.g. the victim) is one of the donors in a mixed DNA profile can have unwanted consequences for the association between donors and cell types. PMID- 27552693 TI - Modified biopolymers as sorbents for the removal of naphthenic acids from oil sands process affected water (OSPW). AB - Oil sands operations consume large volumes of water in bitumen extraction process and produce tailings that express pore water to the surface of tailings ponds known as oil sands process-affected water (OSPW). The OSPW is toxic and cannot be released into the environment without treatment. In addition to metals, dissolved solids, dissolved gases, hydrocarbons and polyaromatic compounds etc., OSPW also contains a complex mixture of dissolved organic acids, referred to as naphthenic acids (NAs). The NAs are highly toxic and react with metals to develop highly corrosive functionalities which cause corrosion in the oil sands processing and refining processes. We have chemically modified keratin biopolymer using polyhedral oligomeric silsesquioxanes (POSS) nanocages and goethite dopant to unfold keratinous structure for improving functionality. The untreated neat keratin and two modified sorbents were characterized to investigate structural, morphological, dimensional and thermal properties. These sorbents were then tested for the removal of NAs from OSPW. The NAs were selectively extracted and quantified before and after sorption process. The biosorption capacity (Q), rejection percentage (R%) and isotherm models were studied to investigate NAs removal efficiency of POSS modified keratin biopolymer (PMKB) and goethite modified keratin biopolymer (GMKB) from aliquots of OSPW. PMID- 27552694 TI - Assessment of metal and bacterial contamination in cultivated fish and impact on human health for residents living in the Mekong Delta. AB - Fish is the main source of animal protein and micronutrients for inhabitants in the lower Mekong River basin. Consumption of fish in the basin ranges from 41 to 51 kg capita(-1) year(-1). Thus, concerns of human health impacts caused by daily intake of metals contained in fish, and the incidence of bacterial contamination from Listeria and Escherichia coli have been raised. This study was conducted to 1) determine concentrations of metals, fecal indicator organisms, and Listeria spp. in cultivated common diet fish, and 2) assess human health risks as results of fish consumption on a daily basis. The results showed significant impacts of metal accumulation in fish especially from the intensive aquaculture. Chemical use to promote the rapid allometric growth of fish was expected to be the explanation for this finding. Concentrations of metals contained in different fish species were not statistically different with the exceptions of Na, Mn, and Zn. This might be due to the mobility of elements in aquaculture farms. Listeria and E. coli log CFU/g were 1.36 +/- 0.11 (standard error) and 1.57 +/- 0.1 s.e., respectively with higher counts observed in samples collected in market sites. Lastly, for human health risk assessment via fish consumption, it was found that hazard quotients of consuming As, Cu, and Zn contained in all fish species could contribute adverse health effects to the local residents (hazard quotients higher than 1). Therefore, risk management measures must be promoted and implemented in all study areas to reduce potential risks to local Vietnamese residents. PMID- 27552695 TI - Spectroscopic study of Se(IV) removal from water by reductive precipitation using sulfide. AB - This study investigates the removal of selenium (IV) from water by reductive precipitation using sodium sulfide at neutral pH. Also, it examines the application of UV light as an activating method to enhance reductive precipitation. Furthermore, this work evaluates the effects of sulfide dose and solution pH on behavior of Se(IV) reduction. Selenium was effectively removed in sulfide solution at both neutral and acidic pH. UV irradiation did not enhance removal efficiency of Se(IV) at conditions tested, but it affected solids morphology and composition. SEM/EDS and XPS results showed that selenite was reduced to elemental Se or Se-S precipitates (e.g. SenS8-n) in sulfide solution. High resolution S 2p XPS spectra suggested the presence of sulfur-containing anions (e.g. S2O3(2-), HSO3(-), etc.) or elemental S (S(0)), monosulfide (S(2-)), and polysulfides (Sn(2-)), which could be produced from sulfide photolysis or reaction with Se. In addition, large aggregates of irregular shape, which suggest Se-S precipitates or elemental sulfur, were found more prominently at pH 4 than at pH 7, and they were more noticeable in the presence of UV with longer reaction times. In addition, XRD patterns showed that gray elemental Se solids were dominant in experiments without UV, whereas Se-S precipitates (Se3S5) with an orange color were found in those with UV. PMID- 27552696 TI - Normalizing surface electromyographic measures of the masticatory muscles: Comparison of two different methods for clinical purpose. AB - PURPOSE: To compare a new normalization technique (wax pad, WAX) with the currently utilized cotton roll (COT) method in surface electromyography (sEMG) of the masticatory muscles. METHODS: sEMG of the masseter and anterior temporalis muscles of 23 subjects was recorded while performing two repetitions of 5s maximum voluntary clenches (MVC) on COT and WAX. For each task, the mean value of sEMG amplitude and its coefficient of variation were calculated, and the differences between the two repetitions computed. The standard error of measurement (SEM) was calculated. For each subject and muscle, the COT-to-WAX maximum activity increment was computed. Participant preference between tasks was also recorded. RESULTS: WAX MVC tasks had larger maximum EMG amplitude than COT MVC tasks (P<0.001), with COT-to-WAX maximum amplitude increments of 61% (temporalis) and 94% (masseter) (P=0.006). WAX MVC had better test-retest repeatability than COT. For both MVC modalities, the mean amplitude (P>0.391) and its coefficient of variation were unchanged (P>0.180). The WAX task was the more comfortable for 18/23 subjects (P=0.007). CONCLUSION: WAX normalization ensures the same stability level of maximum EMG amplitude as COT normalization, but it is more repeatable, elicits larger maximum muscular contraction, and is felt to be more comfortable by subjects. PMID- 27552697 TI - Different molecular signaling sustaining adiponectin action in breast cancer. AB - Obesity is defined as a chronic and excessive growth of adipose tissue. It is increasingly recognized as an oncogenic factor. Adipose tissue, originally thought as a passive depot for fat metabolism, is now identified as an endocrine organ, secreting a wide array of bioactive molecules known as adipocytokines, which act as key mediators in several obesity-associated diseases. Among these adipocytokines, adiponectin has been proposed as having a key role in the pathogenesis of cardiovascular disease and type 2 diabetes along with other diseases such as obesity-associated malignancies, including breast cancer. New insights into the molecular mechanisms linking adiponectin and mammary tumorigenesis could be useful to identify novel therapeutic approaches to be exploited, particularly in obese women. PMID- 27552698 TI - Photoinduced target-like drug reaction to naproxen. PMID- 27552699 TI - An overview of emerging and new psychoactive substances in the United Kingdom. AB - The purpose of this review is to identify emerging or new psychoactive substances (NPS) by undertaking an online survey of the UK NPS market and to gather any data from online drug forums and published literature. Drugs from four main classes of NPS were identified: psychostimulants, dissociative anaesthetics, hallucinogens (phenylalkylamine-based and lysergamide-based materials) and finally benzodiazepines. For inclusion in the review, the 'user reviewers' on drugs forums were selected based on whether or not the particular NPS of interest was used alone or in combination. NPS that were used alone were considered. Each of the classes contained drugs that are modelled on existing illegal materials and will be covered by the UK New Psychoactive Substances Bill in 2016. PMID- 27552700 TI - Experimental study for the reproduction of sudden unintended acceleration incidents. AB - A few cases of the sudden unintended acceleration have been reported over the last few years [1-11] and some of them seemed to be somewhat related to an electronic throttle control (ETC) system [11,12]. In this experimental study, efforts were made to reproduce the cases of sudden unintended acceleration possibly related to the ETC. Typically, an ETC of the engine is managed based on signals from airflow sensor, throttle position sensor and acceleration pedal sensor. With this typical sensor configuration in mind, these sensor signals were checked for noise levels. However, none of them showed any clear relationship with the sudden unintended acceleration mainly due to the robustness of the ETC logic software. As an alternative approach, supply voltage to an engine control unit (ECU) was tempered intentionally to observe any clues for the incidents. The observed results with the supply voltage drop and fluctuation tests were rather astonishing. The throttle valve position went all the way up to 100% for around one second when the battery voltage plunged down to 7V periodically despite that the acceleration pedal position was kept steady. As an effort to confirm the case, multiple tries were made systematically on a chassis dynamometer as well as on the test road. In this paper, detailed procedures and findings are reported accordingly. PMID- 27552701 TI - Dominant psychoactive drugs in the Central European region: A wastewater study. AB - The aim of this study was to analyze 26 various illicit drugs, psychopharmaceuticals and metabolites thereof in sewer from 17 selected wastewater treatment plants (WWTPs) in the Slovak and Czech Republics. Urinary bio-markers used were analyzed using liquid chromatography coupled with the tandem mass spectrometry (LC-MS/MS). We then compared our results with data obtained in other parts of Europe and the world. The present study shows that the Slovak and Czech Republics have one of the highest methamphetamine consumption rates in Europe. Within Slovakia, the highest level of methamphetamine consumption was found in Dunajska Streda with the mean specific load of the drug in sewage being up to 479mg/day/1000 inhabitants; the next highest load was detected in Trnava (354mg/day/1000 inhabitants). The methamphetamine, ecstasy and cannabis consumptions in our study were comparable to those found in other European cities, whereas cocaine consumption was lower. Among all of the studied psychopharmaceuticals, tramadol and venlafaxine were represented in the highest concentrations. The highest mean specific load of tramadol was detected in the spa town of Piestany (371mg/day/1000 inhabitants) and Kosice (372mg/day/1000 inhabitants), while the highest mean loads of venlafaxine were recorded for the towns of Trencin (230mg/day/1000 inhabitants) and Piestany (108mg/day/1000 inhabitants). PMID- 27552702 TI - Blood alcohol analysis alone versus comprehensive toxicological analysis - Systematic investigation of missed co-ingested other drugs in suspected alcohol impaired drivers. AB - Driving under the influence of alcohol and/or drugs (DUID) is a safety issue of increasing public concern. When a police officer has reasonable grounds to classify a driver as impaired, he may arrange for a blood sample to be taken. In many countries, alcohol analysis only is ordered if impairment is suspected to be exclusively due to alcohol while comprehensive toxicological screening will be performed if additional suspicion for other illegal drugs of abuse (DoA) or medicinal drugs is on hand. The aim of the present study was firstly to evaluate whether signs of impairment can be differentiated to be caused by alcohol alone or a combination of alcohol and other driving-impairing drugs and secondly to which extent additional drugs are missed in suspected alcohol-impaired drivers. A total of 293 DUID cases (negative n=41; alcohol positive only, n=131; alcohol+active drug positive, n=121) analyzed in 2015 in the Canton of Zurich were evaluated for their documented impairment symptoms by translating these into a severity score and comparing them applying principle component analysis (PCA). Additional 500 cases suspected for alcohol-impaired driving only were reanalyzed using comprehensive LC-MS/MS screening methods covering about 1500 compounds. Drugs detected were classified for severity of driving impairment using the classification system established in the DRUID study of the European Commission. As partly expected from the pharmacological and toxicological point of view, PCA analysis revealed no differences between signs of impairment caused by alcohol alone and those caused by alcohol plus at least one active drug. Breaking it down to different blood alcohol concentration ranges, only between 0.3 and 0.5g/kg trends could be observed in terms of more severe impairment for combined alcohol and drug intake. In the 500 blood samples retrospectively analyzed in this study, a total of 330 additional drugs could be detected; in some cases up to 9 co ingested ones. In total, 37% of all cases were positive for additional drugs, thereby 15% of classic DoAs and further 9% of prescription drugs with a severe risk to cause driving impairment based on the DRUID classification system. A decision whether signs of impairment are related to alcohol alone or to the combination of alcohol and other drugs is impossible. Taking into consideration the high rate of missed drugs in DUI cases, police should think about increasing the number of DUID cases in countries were sanctioning differs between alcohol and alcohol plus drug impaired driving. PMID- 27552703 TI - Effects of various sample pretreatment procedures on ethyl glucuronide quantification in hair samples: Comparison of positivity rates and appraisal of cut-off values. AB - The quantification of ethylglucuronide (EtG) in hair is nowadays recognized as the approach with the highest diagnostic performance to evaluate harmful drinking. A widely accepted cut-off of 30pg/mg has been selected after several accurate compared studies. While most of the studies that were used to establish the appropriate cut-off value prescribed to cut hair into small segments before their extraction, hair milling has subsequently been identified as the most efficient pretreatment procedure and was therefore recommended in the last Consensus document issued by the Society of Hair Testing. In this study, we initially compared the results obtained with the two sample preparations, namely cutting and milling, both being applied to the same specimens (n=781). Among these, 205 samples produced measurable EtG values with both methods, with differences ranging from -41.7% up to +415% (the mean increase in EtG concentration, switching from cutting to milling, was +62.1% and the median was +42.3%). Among the aforementioned 205 samples, 29 specimens (3.7% of the total 781 samples) produced significantly different outcome, being classified as negative (i.e., below 30pg/mg) if the cutting procedure is used, but largely positive (above 40pg/mg) when milling is used. Subsequently, the positivity rates obtained on a large population dataset (>27,000 samples) with the two procedures, were retrospectively compared using variable cut-offs values. The percentage of head hair samples with EtG concentration exceeding 30pg/mg upon application of the milling procedure shows a 45% increase (from 10.9% to 15.8%) with respect to cutting procedure, whereas the fraction of hair samples with EtG exceeding 40pg/mg (10.5%) overlaps the percentage of positive samples obtained after cutting pretreatment and applying a cut-off of 30pg/mg. On the basis of these results, it would be worth considering the application of cut-off values linked with the pretreatment procedure, taking into account the results of forthcoming inter-laboratory calibrations. PMID- 27552704 TI - Evaluation of trauma patterns in blast injuries using multiple correspondence analysis. AB - Anthropology features little in published literature about blast injuries. Contributions through case studies and experimental research are beginning to expand our understanding of the effect these injuries have on the human skeleton. This study examines blast injury and gunshot related fractures through multiple correspondence analysis (MCA) with the aim of establishing injury patterns between the two types of trauma. Using a sample of 491 individuals from Bosnia, MCA is employed to identify which body regions differentiate between blast or gunshot related fractures. Cranial fractures were more closely associated with gunshot related cases. Post-cranial fractures were associated with blast-related cases. A differentiation in post-cranial and cranial fractures between gunshot and blast related cases was revealed in the samples. The high prevalence of extremity trauma in blast is similar to previous work, but the smaller amount of cranial blast-related fractures differs from previous studies and from what is found in gunshot-related cases. Differentiation of blast and gunshot wound injuries can be made on the human skeleton and can be used to possibly interpret injury mechanism in large skeletal assemblages as well as single cases. PMID- 27552705 TI - Knowns and unknowns in metabolomics identified by multidimensional NMR and hybrid MS/NMR methods. AB - Metabolomics continues to make rapid progress through the development of new and better methods and their applications to gain insight into the metabolism of a wide range of different biological systems from a systems biology perspective. Customization of NMR databases and search tools allows the faster and more accurate identification of known metabolites, whereas the identification of unknowns, without a need for extensive purification, requires new strategies to integrate NMR with mass spectrometry, cheminformatics, and computational methods. For some applications, the use of covalent and non-covalent attachments in the form of labeled tags or nanoparticles can significantly reduce the complexity of these tasks. PMID- 27552706 TI - Massively parallel WRNN reconstructors for spectrum recovery in astronomical photometrical surveys. AB - The investigation of solar-like oscillations for probing star interiors has enjoyed a tremendous growth in the last decade. Once observations are over, the most notable difficulties in properly identifying the true oscillation frequencies of stars are due to the gaps in the observation time-series and the intrinsic stellar granulation noise. This paper presents an innovative neuro wavelet reconstructor for the missing data of photometric signals. Firstly, gathered data are transformed using wavelet operators and filters, and this operation removes granulation noise, then we predict missing data by a composite of two neural networks, which together allow a "forward and backward" reconstruction. This resulting error is greatly lower than the absolute a priori measurement error. The devised reconstruction approach gives a signal that is better suited to be Fourier transformed when compared with other existing methods. PMID- 27552707 TI - Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY 876. AB - Despite the long-known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1 selective small-molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high-throughput screen against a library of ~3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N-(1H-pyrazol-4-yl)quinoline-4-carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure-activity relationship explorations, single-digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY-876 [N4 -[1-(4-cyanobenzyl) 5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-7-fluoroquinoline-2,4 dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo. PMID- 27552708 TI - Mycobacterium abscessus scleritis after a Baerveldt glaucoma implant. PMID- 27552709 TI - Telomere length-related gene ACYP2 polymorphism is associated with the risk of HAPE in Chinese Han population. AB - BACKGROUND: High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea-level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE. METHODS: A total of 265 patients and 303 healthy controls were enrolled in our case-control study. Six SNPs were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. RESULTS: Using chi-squared tests, we found that the minor allele G of rs11896604 is significantly associated with a decreased risk of HAPE [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.65-1.16, p = 0.048]. We also found that the 'A/A' genotype of rs12615793 is associated with a decreased risk of HAPE based on the recessive model (OR =0.28; 95% CI = 0.09-0.88; p = 0.017). Additionally, the 'G/G' genotype of rs11896604 was found to be associated with a decreased risk of HAPE based on the codominant model (OR =0.26; 95% CI = 0.08-0.79; p = 0.025) and recessive model (OR =0.25; 95% CI = 0.08-0.77; p = 0.007). However, only rs11896604 remained significant after Bonferroni correction (p < 0.0083). CONCLUSIONS: The present study found that the ACYP2 gene polymorphism significantly decreased the risk of HAPE. Copyright (c) 2016 John Wiley & Sons, Ltd. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27552710 TI - Does one day of drinking matter? 21st birthday drinking predicts subsequent drinking and consequences. AB - OBJECTIVE: There has been ample research on college student risks and consequences related to 21st Birthday Drinking. To date, no studies we are aware of have examined how 21st birthday drinking impacts subsequent drinking and related consequences. This study evaluates the effect of a single night of drinking on peak drinking, heavy drinking, and negative consequences over 12months following the event. Furthermore, we examine if typical drinking behavior prior to 21st birthday moderates the relationship between the event drinking and subsequent use. METHOD: Participants included 599 college students (46% male) who intended to consume at least five/four drinks (men/women respectively) on their 21st birthday. Screening and baseline assessments were completed approximately four weeks before turning 21. A follow-up assessment was completed approximately one week after students' birthdays and every 3months for one year thereafter. RESULTS: Those who drank more on their 21st birthday, also reported higher peak consumption, increased likelihood of consequences, and increased number of consequences throughout the year. Additionally, baseline peak drinking moderated the relationship such that those who drank less at peak occasion prior to turning 21 showed the strongest effects of 21st BD drinking on subsequent consumption. CONCLUSIONS: 21st BD drinking could impact subsequent choices and problems related to alcohol. Interventions are warranted and implications discussed. PMID- 27552712 TI - Simple mathematical model of sacroiliac screws safe-zone-Easy to implement by pelvic inlet and outlet views. AB - Percutaneous sacral screw fixation is the mainstay of posterior pelvic ring fixation. This study quantifies the accuracy of fluoroscopic screw placement using post-operative CT scans and redefines the fluoroscopic safe zone using a mathematical calculation obtained from Inlet and outlet images. The authors hypothesized that a mathematical calculation of screw placement within the ala will improve accuracy of screw placement. A retrospective review of consecutive patients admitted to a level 1 trauma center with pelvic fractures fixed with iliosacral screws from January 2011 to December 2014 was performed. Accuracy of screw placement was determined by comparing fluoroscopy to post-operative CT scans. A mathematical calculation of screw position within the sacral ala was applied to determine assess screw position and compared to CT findings. Ninety four patients with 156 screws met inclusion criteria, of which 50 (32.0%) had a cortical breech on CT. The sensitivity and specificity of the inlet-outlet safe zone using mathematical calculation were 97.1% and 84.0%, respectively. The positive and negative predictive values were 92.7% and 93.3%, respectively. Overall accuracies of the radiographic inlet-outlet and lateral safe zones were 92.9% and 70.0%, respectively (p-value = 0.004). Sacral dysmorphism was not found to be associated with sacral cortical breech. A Simple mathematical calculation (screw position relative to percentage of bone width) on the inlet-outlet provides an accurate way to predict the accuracy of sacroiliac screws. The method is easy to implement, part of the surgery work-flow, and provides higher accuracy than relying on subjective interpretation of inlet, outlet, and lateral images. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1478-1484, 2017. PMID- 27552713 TI - Nursing students' well-being using the job-demand-control model: A longitudinal study. AB - BACKGROUND: Students' well-being is very important both for students and institutions. However, this field lacks longitudinal research, which focuses on the change of nursing students' well-being during their study. In order to asses such changes the four study types according to Job-Demand-Control-Support-model were used: passive, high-strain, low-strain, and active. DESIGN: A longitudinal design was employed: participants were recruited in 2010/2011 (phase I) and at the end of their study in 2012 (phase II). SETTINGS: The study was performed in one school of health care in a university of applied sciences in Finland. PARTICIPANTS: The final sample consisted of 135 nursing students (BSc) who started their study either in September 2008 or January 2009, and finished in December 2011 or May 2012. METHODS: The participants responded to the same close ended questionnaire in both phases. RESULTS: The majority of the participants experienced the study type as low-strain (phase I: 61.5%; phase II: 48.2%). The distribution according to their study type did not change substantially between both phases, although 42.2% of the participants changed their study type. The major changes of study types were from low-strain to others (21.4%), and from other study types to the active one (12.6%). CONCLUSIONS: The results indicate that the majority of students do not change their study type and consequentially their well-being during their study, which is in contrast with previous research. Special attention should be put to the identification of students who change their study type to high-strain or remain in it. PMID- 27552711 TI - PCB exposure and cochlear function at age 6 years. AB - Epidemiological studies have documented adverse associations between exposure to polychlorinated biphenyls (PCBs) and otological outcomes. Previously, we documented decreased distortion product otoacoustic emission (DPOAE) levels in children exposed to PCBs, up to the age of 45 months, amongst a cohort of children in eastern Slovakia. The objective of the present study is to evaluate cochlear dysfunction at 72 months of age in 214 children from this same cohort and to compare the otoacoustic test sensitivity to that of pure tone audiometry (PTA). The association between DPOAE, PTA, and PCBs was estimated by means of multivariate ANOVA (MANOVA) and linear regression models. ROC curves were computed to estimate the DPOAE-test power in children. The DPOAE level at 72 months was related to PCB-153 serum levels. The DPOAE Input/Output function test at mid-frequency (2kHz) has shown instead nonmonotonic dependence on PCB exposure, for the left ears of children, over the whole growth curve. No significant association was found between PTA hearing levels and PCB-153 concentration. High diagnostic power of the DPOAE-test was found in children, similar to that found by the same authors in adults. In conclusions the DPOAE-PCB correlation obtained at 72 months is similar to that at 45 months suggesting a permanent and stable ototoxic effect of the PCB exposure. The lack of statistical significance of the PCB-PTA correlation suggests that DPOAEs are sensitive biomarkers of cochlear damage. PMID- 27552714 TI - Nursing student and professor perceptions and assessments of the achievement of practicum competencies: A mixed method approach. AB - Within the context of the European Higher Education Area's requirement of competency-based assessments, the objective of the present study was to evaluate the Nursing Degree Practicum experience at the University of Girona (Spain) and ascertain student and faculty perceptions of the degree of competency achieved as a result of the practicum. This cross-sectional, descriptive, study combined quantitative analysis of a questionnaire and qualitative analysis of focus group comments. In the quantitative part of the study, 163 fourth-year nursing students completed the questionnaire; the qualitative analysis was derived from a focus group of 5 students and 5 professors. On the questionnaire, overall practicum evaluation was 8.39 on a 10-point Likert scale; scores evaluating the nurse mentor/instructor and nursing professor were 8.43 and 7.98, respectively. The geriatrics practicum experience received the lowest overall score (7.81), while the surgical practicum received the lowest score on the adequacy of knowledge acquired in the classroom in previous courses (5.54). The best scores were earned by the mental health and intensive/emergency care practicum experiences (a mean of 9.05 and 8.70, respectively). Students and professors in the focus group agreed that the practicum met the Nursing degree program's competency goals, highlighting practical activity as the best methodology to evaluate competencies. Participants highlighted the importance of reflective practice and the role of the nurse mentor/instructor in student learning, and indicated that it is essential for the university and the health care centers where students take practicum courses to maintain a strong relationship and good communication. Finally, feedback from the nurse mentor/instructor and Nursing professor was very important to students, both to motivate them and to help them learn. PMID- 27552715 TI - Using video podcasting to enhance the learning of clinical skills: A qualitative study of physiotherapy students' experiences. AB - BACKGROUND: Video podcasts, or vodcasts are increasingly used by a range of healthcare professions in the mastery of new skills. Little is known about the experiences of using vodcasts in physiotherapy education. Traditional pedagogic strategies have been employed in order to master those skills required for physiotherapy practice. There have been advances in the use of technology in medical education in the nursing, dentistry and medical fields. Vodcasts offer great versatility and potential when used as a pedagogical tool, embedded within a physiotherapy curriculum. AIM: To explore students' experiences of using technology enhanced learning, namely vodcasts, in the Physiotherapy curriculum to develop the learning of clinical skills. METHOD: A series of focus groups were carried out with undergraduate and pre-registration physiotherapy students (n=31). FINDINGS: Students valued the versatility and audio-visual nature of vodcasts; helpful in revising for practical examinations and practising their skills prior to, during and after taught skills classes. Watching and practising simultaneously allowed students to practice repeatedly and formulate a process for each skill. When learning a new skill, a combination of teaching and learning approaches was favoured, marrying traditional approaches with those that utilise technology. CONCLUSIONS: This study's findings add to the existing body of evidence in skills based teaching and support a multi-media, blended approach in those disciplines involved in the learning and teaching of clinical skills. PMID- 27552716 TI - Subtissue Imaging and Thermal Monitoring of Gold Nanorods through Joined Encapsulation with Nd-Doped Infrared-Emitting Nanoparticles. AB - Encapsulation of gold nanorods together with Nd-doped fluorescent nanoparticles in a biocompatible polymer creates multifunctional nanostructures, whose infrared fluorescence allows their subcutaneous localization in biological tissues while also adding the ability to measure the temperature from the emitted light in order to better monitor the light-to-heat conversion of the gold nanorods during photothermal therapy. PMID- 27552717 TI - White matter structure in the uncinate fasciculus: Implications for socio affective deficits in Autism Spectrum Disorder. AB - Individuals with Autism Spectrum Disorder (ASD) have social and communication deficits and difficulties regulating emotions. The brain bases of these socio affective deficits are not yet clear, but one candidate is structural connectivity in the left uncinate fasciculus, which connects limbic temporal and frontal areas thought to be involved in socio-affective processing. In this study, we assessed white matter structure in the left and right uncinate fasciculus in 18 high-functioning individuals with ASD and 18 group-matched typically developing (TD) controls using Diffusion Tensor Imaging. To test specificity of the associations, we also examined the association between both uncinate fasciculi and restricted and repetitive behaviors. Compared to TD individuals, individuals with ASD had significantly lower fractional anisotropy (FA) in the left and right uncinate. Group status significantly moderated the association between left uncinate and socio-affective deficits, indicating that within the ASD group, FA was associated with socio-affective deficits: Individuals with ASD with lower FA in the left uncinate had significantly more social and emotion regulation deficits. There was no association with restricted and repetitive behaviors. This study provides evidence that the left uncinate may play a critical role in socio-affective skills in individuals with ASD. PMID- 27552718 TI - Advanced nitrogen removal from landfill leachate via Anammox system based on Sequencing Biofilm Batch Reactor (SBBR): Effective protection of biofilm. AB - High levels of organics negatively affect Anammox for treating landfill leachate. To enhance the ability of Anammox to survive against adverse environments, a lab scale two-stage Anammox system using a Sequencing Biofilm Batch Reactor was applied to treat mature landfill leachate under 35 degrees C. Over 107days, with influent total nitrogen (TN) and chemical oxygen demand (COD) concentrations of 3000+/-100 and 3000+/-100mg/L, effluent TN was below 20mg/L. For extracellular polymeric substance (EPS) of Anammox, slime-EPS and loosely-bound-EPS of floccules were both higher than biofilm, while tight-bound-EPS of biofilm was significantly higher, contributing to biofilm formation. Quantitative microbial analysis showed that as influent COD increased, Anammox gene ratios of biofilm increased from 1.34% to 13.28%; the gene ratios of floccule first increased, then decreased to 3.88%. This indicated that Anammox and heterotrophic bacteria could coexist because of the biofilm, leading to stable nitrogen removal performance, even when organics were present. PMID- 27552719 TI - Combining simultaneous nitrification-endogenous denitrification and phosphorus removal with post-denitrification for low carbon/nitrogen wastewater treatment. AB - Due to the limited nutrient removal from low carbon/nitrogen (?4) wastewater, a process combined simultaneous nitrification-endogenous denitrification and phosphorus removal (SNDPR) with post-denitrification (PD) in a SBR was proposed for deep-level nutrient removal without external carbon addition. SNDPR driven by PAOs and GAOs reduced PO4(3-)-P (98.3%) and partial TN (59.0%) at low DO conditions (0.5+/-0.1mg/L), and post-dentrification achieved further NOX(-) (produced by SNDPR) removal (24.0%) anoxically by utilizing the residual intracellular polymers in GAOs. Combined control of anaerobic/aerobic/anoxic durations and low DO inhibition to aerobic GAOs and NOB conducted partial nitrification-endogenous denitrification (PNED) (66%), which saved 44.3% intracellular polymers to further reduce 64% TN in effluent. After 115-day operation, the average effluent PO4(3-)-P and TN concentrations were 0.4 and 3.9mg/L, respectively, with 92.1% of TN removal. Highly enriched PAOs (36%+/-2%), GAOs (22%+/-2%) and AOB (15%+/-3%) over NOB (3%+/-1%) facilitated P uptake, PNED and post-denitrification in the SNDPR-PD system. PMID- 27552720 TI - An enhanced anaerobic membrane bioreactor treating bamboo industry wastewater by bamboo charcoal addition: Performance and microbial community analysis. AB - In this study, two anaerobic membrane bioreactors (AnMBRs) were operated for 150days to treat bamboo industry wastewater (BIWW), and one of them was enhanced with bamboo charcoal (B-AnMBR). During the steady period, average chemical oxygen demand (COD) removal efficiencies of 94.5+/-2.9% and 89.1+/-3.1% were achieved in B-AnMBR and AnMBR, respectively. The addition of bamboo charcoal (BC) increased the amount of biomass and improved the performance of the systems. A higher biogas production and methane yield were also observed in B-AnMBR. Regarding the issue of membrane fouling, BC lowered the soluble microbial product (SMP) content by approximately 62.73mg/L and decreased the membrane resistance, thereby mitigating membrane fouling. Analysis of the microbial communities demonstrated that BC increased the microbial diversity and promoted the activity of Methanosaeta, Methanospirillum, and Methanobacterium, which are dominant in methane production. PMID- 27552721 TI - Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China. AB - This study aimed to investigate the epidemiological features of HIV-infected subjects co-infected with HBV/HCV in Fujian Province, southeastern China, and identify the risk factors. Blood samples were collected from 2,028 HIV antibody positive subjects in Fujian Province. Serum HBsAg and anti-HCV antibody were detected, and CD4+ T cell count was measured. Of the 2,028 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections was 16.22%, 3.7%, and 0.79%, respectively. Man (OR = 1.912, 95% CI: 1.371-2.667), key population (OR = 0.756, 95% CI: 0.57-0.976) and detainee (OR = 0.486, 95% CI: 0.259-0.909) were risk factors of HIV-HBV co-infection, and man (OR = 2.227, 95% CI: 1.096 4.525), minority (OR = 5.04, 95% CI: 1.696-14.98), junior high school or lower education (OR = 2.32, 95% CI: 1.071-5.025), intravenous drug use (OR = 38.46, 95% CI: 11.46-129.11) and detainee (OR = 5.687, 95% CI: 2.44-13.25) were risk factors of HIV-HCV co-infection. In addition, a lower mean CD4+ T cell count was measured in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects among the untreated individuals, while in the treated populations, a higher mean CD4+ T cell count was detected in HIV/HBV and HIV/HCV co-infected subjects than in HIV infected subjects. HIV co-infection with HBV or HCV, notably HIV-HBV co infection, is widespread in southeastern China. Hepatitis virus screening should be included in monitoring of HIV infection, and HIV and hepatitis virus co infection should be considered during the development of HIV antiretroviral therapy scheme. J. Med. Virol. 89:443-449, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27552722 TI - Twelve-year follow-up of mandibular incisor stability: Comparison between two bonded lingual orthodontic retainers. AB - OBJECTIVE: To compare the long-term outcome 9 years after removal of two different types of fixed retainers used for stabilization of the mandibular anterior segment. MATERIALS AND METHODS: Sixty-four children who had undergone orthodontic treatment with fixed appliances in both arches were divided into two groups depending on which kind of retainer being used. Twenty-eight of the patients had a canine-to-canine retainer bonded to the canines and 36 had a bonded twistflex retainer 3-3, bonded to each tooth. Measurements were made on study models and lateral head radiographs, before and after treatment, 6 years after treatment, and 12 years after treatment, with a mean of 9.2 years after removal of the retainers. RESULTS: No significant differences were found between the two groups at the long-term follow-up according to Little's Irregularity Index or available space for the mandibular incisors. The overjet and overbite were reduced after treatment in both groups and stayed stable throughout the observation period. Also, no differences in bonding failures between the two retainers were found. CONCLUSIONS: Both a canine-to-canine retainer bonded only to the canines and a twistflex retainer 3-3 bonded to each tooth can be recommended. However, neither of the retention types prevented long-term changes of mandibular incisor irregularity or available space for the mandibular incisors after removal of the retainers. PMID- 27552724 TI - Quantifying accommodation to prosthesis interventions in persons with lower limb loss. AB - Determining the appropriate amount of accommodation time is an important component of research protocol design in the field of limb prosthetics. Insufficiently short or excessively long accommodation periods may limit the external validity of findings and/or the economic efficiency and ethical innocuousness of a study. However, issuing general recommendations is difficult, as individual accommodation periods are affected by subject characteristics, the nature of the intervention, and possibly a number of environmental factors. We are discussing an approach to determine individual accommodation times based on the assumption that the process of becoming accustomed to a prosthetic intervention follows a similar exponential "learning curve" as many other learning processes that have been previously investigated. Initial data collected with a small subject sample gives some indication that gait cycle symmetry changes along the hypothesized curve trajectory. If those preliminary results can be confirmed it may be possible to extrapolate a subject's eventual level of accommodation based on a small data set that is easily collected during the first twenty minutes after introducing a prosthetic intervention. PMID- 27552723 TI - Where does the neighborhood go? Trust, social engagement, and health among older adults in Baltimore City. AB - Trust is often cited as a necessary predecessor of social engagement, and a public-health good. We question those suppositions through analysis of the life histories of lower-income older adults aging in place in Baltimore. These people desired to continue living independently, but also expressed a complex mix of trust and mistrust in their neighbors, neighborhoods, and broader environments. This was the product of interrelated processes of multilevel physical and social changes over time and space - and, we argue, often featured a "healthy mistrust" that pushed participants to pursue personally meaningful forms of social engagement, whether new or continued. PMID- 27552725 TI - Influence of a rhythmic auditory stimulation on asymptomatic gait. AB - The direct effects of a rhythmic auditory stimulation (RAS) on the gait of asymptomatic subjects are not clear. Previous studies only showed modifications in the gastrocnemius activity, inconsistent effects on temporal parameters, and no modification of spatial parameters. Furthermore, the influence of RAS on kinematics and kinetics has only been reported in pathological gait. The objective of this study was to perform a full comparison of gait characteristics in asymptomatic subjects at preferred and reduced walking speed between without and with RAS conditions. Spatiotemporal parameters, kinematics, kinetics and EMG signals datasets were collected for each condition. RAS conditions were obtained by asking subjects to walk on metronomic beats. 17 asymptomatic subjects were included in the study (12M/5W, 37.4+/-15.7years, 74.0+/-14.8kg, 1.77+/-0.09m). Comparisons between without and with RAS conditions were then performed using the Statistical Parametric Mapping method. For all combined subjects, the effect of RAS was limited whatever the walking speed. Meanwhile, global effects were observed for kinematics, kinetics and EMG at both spontaneous and reduced walking speed, which can only be explained by covariances (i.e., no effect on individual time-series). The use of RAS to impose a specific cadence matching the desired walking speed (e.g., to collect normative data) appears thus possible, as none parameters were modified individually. However, RAS should be used with caution taking into account covariances (i.e., muscle synergy or joint coordination patterns). This study has to be extended to a larger number of subjects to confirm these observations. PMID- 27552726 TI - Managing the lipid profile of coronary heart disease patients. AB - INTRODUCTION: Lipid profile management is even more critical in patients treated for secondary prevention, since patients with established coronary heart disease are at higher risk of developing events. Current guidelines encourage lifestyle modification and patient engagement in disease prevention. However, the American College of Cardiology/American Heart Association guidelines seem to differ considerably from their predecessors, having an impact on clinical practice of lipid management. Area covered: This review article discusses and provides a summary of the current recommendations for lipid profile management in patients with coronary heart disease, with a view to present lifestyle modification and novel treatment strategies, and to indicate areas of dispute among recent guidelines. Expert commentary: Existing controversies between current guidelines concerning treatment goals and therapeutic decisions may have potential implications on the clinical management of patients. In the meantime, we eagerly wait for the results of randomized controlled trials evaluating promising, potent, safe and prolonged drugs that are in progress. PMID- 27552727 TI - Endoscopic management of combined malignant biliary and gastric outlet obstruction. AB - Patients with periampullary cancer or gastric cancer often develop malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), and combined MBO and GOO is not rare in these patients. Combined MBO and GOO is classified by its location and sequence, and treatment strategy can be affected by this classification. Historically, palliative surgery, hepaticojejunostomy and gastrojejunostomy were carried out, but the current standard treatment is combined transpapillary stent and duodenal stent placement. Although a high technical success rate is reported, the procedure can be technically difficult and duodenobiliary reflux with subsequent cholangitis is common after double stenting. Recent development of endoscopic ultrasound (EUS)-guided procedures enables the management of MBO as well as GOO under EUS guidance. EUS-guided biliary drainage is now increasingly reported as an alternative to percutaneous transhepatic biliary drainage in failed endoscopic retrograde cholangiopancreatography (ERCP), and GOO is one of the major reasons for failed ERCP. In addition to EUS-guided biliary drainage, the feasibility of EUS-guided double-balloon-occluded gastrojejunostomy bypass for MBO was recently reported, and EUS-guided double stenting can potentially become the treatment of choice in the future. However, as each procedure has its advantages and disadvantages, treatment strategy should be selected based on the type of obstruction and the prognosis and performance status of the patient. PMID- 27552728 TI - Filtering activity on a pure culture of Vibrio alginolyticus by the solitary ascidian Styela plicata and the colonial ascidian Polyandrocarpa zorritensis: a potential service to improve microbiological seawater quality economically. AB - We investigated and compared, by laboratory experiments, the filter-feeding activity on bacteria by the solitary ascidian Styela plicata and the colonial ascidian Polyandrocarpa zorritensis. Clearance rates and retention efficiencies were estimated by using, as only food source, the bacterial species Vibrio alginolyticus selected on account of its importance in aquaculture pathogenicity. The Cmax was 1.4+/-0.17Lh-1g-1 DW for S. plicata and 1.745Lh-1g-1 DW for P. zorritensis. The highest retention efficiency was 41% corresponding to a removed bacterial biomass of 16.34+1.71 MUgCL-1g-1 DW for P. zorritensis and 81% corresponding to a bacterial biomass of 32.28+2.15 MUgCL-1g-1 DW for S. plicata. Styela plicata resulted higher efficient than P. zorritensis in removing V. alginolyticus from seawater in experimental tanks, thus representing a more suitable biofilter to restore the quality of microbiologically contaminated waters including those where aquaculture is practiced. Present laboratory experiments represent the first contribution to the comparison of the filtration activity of the two ascidians, as well as to characterize the filtration process on bacterioplankton and pone the basis for future field works aimed to restore bacteriological polluted seawater. PMID- 27552729 TI - Remote sensing of diffuse attenuation coefficient patterns from Landsat 8 OLI imagery of turbid inland waters: A case study of Dongting Lake. AB - The diffuse attenuation coefficient, Kd(lambda), is an important optical property. Environmental change and anthropogenic activities, however, have made it challenging to accurately assess Kd(lambda) patterns in the extremely turbid inland waters. We addressed this challenge by using new Landsat 8 Operational Land Imager (OLI) imagery. For the bio-optical complexity of water, we proposed an empirical band-ratio algorithm for estimating Kd(490) using our in situ measurements. Based on the acceptable performance of an OLI image-based atmospheric correction and Kd(490) validation, the algorithm was then applied to OLI images to estimate Kd(490) patterns from April 2013 to April 2016, leading to several key findings: (1) Spatial-temporal patterns of Kd(490) varied significantly in Dongting Lake. The temporal heterogeneity of Kd(490) could be explained primarily by surface-runoff changes driven by regional precipitation. The spatial heterogeneity was due to sediment resuspension, resulting from sand dredging and shipping activities; (2) Kd(490) values that were inversed at the intersection of Dongting Lake and Yangtze River were observed for the first time near the Chengliji site and resulted from the opposing temporal cycle of Kd(490) variations between Dongting Lake and the Yangtze River; (3) There was a significant positive correlation between Kd(490) and total suspended matter (TSM). This confirms that TSM often plays a principal role in the attenuation of light in extremely turbid water bodies; (4) The empirical band-ratio algorithm worked well, not only for the broader Landsat archives, but also for the narrower Sentinel-2/3 for Kd(490) estimation, which demonstrates that the algorithm could be used to quantitatively monitor multi-decade records of Landsat observations and future applications of inland water quality in turbid inland waters, such as Dongting Lake and Poyang Lake. PMID- 27552730 TI - Identification and influence of spatio-temporal outliers in urban air quality measurements. AB - Forty eight potential outliers in air pollution measurements taken simultaneously in Detroit, Michigan, USA and Windsor, Ontario, Canada in 2008 and 2009 were identified using four independent methods: box plots, variogram clouds, difference maps, and the Local Moran's I statistic. These methods were subsequently used in combination to reduce and select a final set of 13 outliers for nitrogen dioxide (NO2), volatile organic compounds (VOCs), total benzene, toluene, ethyl benzene, and xylene (BTEX), and particulate matter in two size fractions (PM2.5 and PM10). The selected outliers were excluded from the measurement datasets and used to revise air pollution models. In addition, a set of temporally-scaled air pollution models was generated using time series measurements from community air quality monitors, with and without the selected outliers. The influence of outlier exclusion on associations with asthma exacerbation rates aggregated at a postal zone scale in both cities was evaluated. Results demonstrate that the inclusion or exclusion of outliers influences the strength of observed associations between intraurban air quality and asthma exacerbation in both cities. The box plot, variogram cloud, and difference map methods largely determined the final list of outliers, due to the high degree of conformity among their results. The Moran's I approach was not useful for outlier identification in the datasets studied. Removing outliers changed the spatial distribution of modeled concentration values and derivative exposure estimates averaged over postal zones. Overall, associations between air pollution and acute asthma exacerbation rates were weaker with outliers removed, but improved with the addition of temporal information. Decreases in statistically significant associations between air pollution and asthma resulted, in part, from smaller pollutant concentration ranges used for linear regression. Nevertheless, the practice of identifying outliers through congruence among multiple methods strengthens confidence in the analysis of outlier presence and influence in environmental datasets. PMID- 27552731 TI - Evaluation of precipitation input for SWAT modeling in Alpine catchment: A case study in the Adige river basin (Italy). AB - Precipitation is often the most important input data in hydrological models when simulating streamflow. The Soil and Water Assessment Tool (SWAT), a widely used hydrological model, only makes use of data from one precipitation gauge station that is nearest to the centroid of each subbasin, which is eventually corrected using the elevation band method. This leads in general to inaccurate representation of subbasin precipitation input data, particularly in catchments with complex topography. To investigate the impact of different precipitation inputs on the SWAT model simulations in Alpine catchments, 13years (1998-2010) of daily precipitation data from four datasets including OP (Observed precipitation), IDW (Inverse Distance Weighting data), CHIRPS (Climate Hazards Group InfraRed Precipitation with Station data) and TRMM (Tropical Rainfall Measuring Mission) has been considered. Both model performances (comparing simulated and measured streamflow data at the catchment outlet) as well as parameter and prediction uncertainties have been quantified. For all three subbasins, the use of elevation bands is fundamental to match the water budget. Streamflow predictions obtained using IDW inputs are better than those obtained using the other datasets in terms of both model performance and prediction uncertainty. Models using the CHIRPS product as input provide satisfactory streamflow estimation, suggesting that this satellite product can be applied to this data-scarce Alpine region. Comparing the performance of SWAT models using different precipitation datasets is therefore important in data-scarce regions. This study has shown that, precipitation is the main source of uncertainty, and different precipitation datasets in SWAT models lead to different best estimate ranges for the calibrated parameters. This has important implications for the interpretation of the simulated hydrological processes. PMID- 27552732 TI - Trophic ecology influence on metal bioaccumulation in marine fish: Inference from stable isotope and fatty acid analyses. AB - The link between trophic ecology and metal accumulation in marine fish species was investigated through a multi-tracers approach combining fatty acid (FA) and stable isotope (SI) analyses on fish from two contrasted sites on the coast of Senegal, one subjected to anthropogenic metal effluents and another one less impacted. The concentrations of thirteen trace metal elements (As, Cd, Co, Cr, Cu, Fe, Li, Mn, Ni, Pb, Sn, U, and Zn) were measured in fish liver. Individuals from each site were classified into three distinct groups according to their liver FA and muscle SI compositions. Trace element concentrations were tested between groups revealing that bioaccumulation of several metals was clearly dependent on the trophic guild of fish. Furthermore, correlations between individual trophic markers and trace metals gave new insights into the determination of their origin. Fatty acids revealed relationships between the dietary regimes and metal accumulation that were not detected with stable isotopes, possibly due to the trace metal elements analysed in this study. In the region exposed to metallic inputs, the consumption of benthic preys was the main pathway for metal transfer to the fish community while in the unaffected one, pelagic preys represented the main source of metals. Within pelagic sources, metallic transfer to fish depended on phytoplankton taxa on which the food web was based, suggesting that microphytoplankton (i.e., diatoms and dinoflagellates) were a more important source of exposition than nano- and picoplankton. This study confirmed the influence of diet in the metal accumulation of marine fish communities, and proved that FAs are very useful and complementary tools to SIs to link metal accumulation in fish with their trophic ecology. PMID- 27552733 TI - Water consumption related to different diets in Mediterranean cities. AB - Providing the sustainable development goals (SDGs) water, food and energy security to cities relies strongly on resource use outside city borders. Many modern cities have recently invested in a sustainable urban water system, and score high in international city rankings regarding water management and direct urban water use. However, these rankings generally neglect external resource use for cities. Here we quantify the water resources related to food consumption in thirteen cities located in Mediterranean countries, by means of the water footprint (WF) concept. These WFs amount from 3277l per capita per day (l/cap/d) to 5789l/cap/d. These amounts are about thirty times higher than their direct urban water use. We additionally analyse the WF of three diet scenarios, based upon a Mediterranean dietary pattern. Many authors identify the Mediterranean diet as cultural heritage, being beneficial for human health and a model for a sustainable food system. The first diet scenario, a healthy Mediterranean diet including meat, leads to WF reductions of -19% to -43%. The second diet scenario (pesco-vegetarian), leads to WF reductions of -28% to -52%. The third diet scenario (vegetarian), leads to WF reductions of -30% to -53%. In other words, if urban citizens want to save water, they need to look at their diets. PMID- 27552734 TI - Impact of VOC removal by activated carbon on biodegradation rates of diesel, Syntroleum and biodiesel in contaminated sand. AB - The degradation of conventional diesel (D), synthetic diesel (Syntroleum), and pure fish biodiesel (B100) by indigenous microbes was investigated in laboratory microcosms containing contaminated sand. The fate of volatiles and the influence of volatilization on degradation rates were examined by placing activated carbon (AC) in microcosm headspaces to sorb volatiles. Three AC regimes were compared: no activated carbon (NAC), regular weekly AC change (RAC), and frequent AC change (FAC), where the frequency of activated carbon exchange declined from daily to weekly. Generally, the alternative fuels were biodegraded faster than diesel fuel. Hydrocarbon mineralization percentages for the different fuel types over 28days were between 23% (D) and 48% (B100) in the absence of activated carbon, decreased to 12% (D) - 37% (B100) with weekly AC exchange, and were further reduced to 9-22% for more frequent AC change. Sorption of volatiles to AC lowered their availability as a substrate for microbes, reducing respiration. Volatilization was negligible for the biodiesel. A mass balance for the carbon initially present as hydrocarbons in microcosms with activated carbon in the head space was on average 92% closed, with 45-70% remaining in the soil after 4weeks, 9-37% mineralized and up to 12% volatilized. Based on nutrient consumption, up to 29% of the contaminants were likely converted into biomass. PMID- 27552735 TI - Seasonal variations and source apportionment of complex polycyclic aromatic hydrocarbon mixtures in particulate matter in an electronic waste and urban area in South China. AB - Complex polycyclic aromatic hydrocarbon (PAH) mixtures including parent PAHs, high molecular weight PAHs (MW 302 PAHs), and halogenated PAHs (HPAHs) were measured in particulate matter (PM) in an urban area and a rural electronic waste area in South China. The concentrations of MW < 302 PAHs at two sites were not significantly different with annual means of 23.2 +/- 17.2 and 33.7 +/- 29.0 ng/m3, respectively. However the concentrations of both MW 302 PAHs (5.35 +/- 3.72 ng/m3) and HPAH (49.9 pg/m3) were significantly higher at the e-waste site than the urban site (2.81 +/- 2.36 ng/m3 and 28.2 +/- 28.5 pg/m3), suggesting e waste recycling being a significant source of these PAHs. The majority of PAHs exhibited higher concentrations in winter and spring and lower concentrations in fall and summer. Meteorological conditions and increased emissions of PAHs in northern China due to domestic heating in colder seasons are important factors influencing the PAH seasonal variations. Source apportionment by the chemical mass balance (CMB) model indicated that residential stoves (coal combustion), industrial boilers (coal combustion), biomass burning, and vehicular emission accounted for 38 +/- 14%, 30 +/- 11%, 22 +/- 22%, and 10 +/- 7% of the PAHs in the urban PM, respectively. Comparable contributions from these sources were also observed for PM at the e-waste site. PAH emission factors are needed for primitive e-waste recycling to further understand the importance of this source to ambient air. PMID- 27552736 TI - Biogenic volatile organic compound emissions along a high arctic soil moisture gradient. AB - Emissions of biogenic volatile organic compounds (BVOCs) from terrestrial ecosystems are important for the atmospheric chemistry and the formation of secondary organic aerosols, and may therefore influence the climate. Global warming is predicted to change patterns in precipitation and plant species compositions, especially in arctic regions where the temperature increase will be most pronounced. These changes are potentially highly important for the BVOC emissions but studies investigating the effects are lacking. The aim of this study was to investigate the quality and quantity of BVOC emissions from a high arctic soil moisture gradient extending from dry tundra to a wet fen. Ecosystem BVOC emissions were sampled five times in the July-August period using a push pull enclosure technique, and BVOCs trapped in absorbent cartridges were analyzed using gas chromatography-mass spectrometry. Plant species compositions were estimated using the point intercept method. In order to take into account important underlying ecosystem processes, gross ecosystem production, ecosystem respiration and net ecosystem production were measured in connection with chamber based BVOC measurements. Highest emissions of BVOCs were found from vegetation communities dominated by Salix arctica and Cassiope tetragona, which had emission profiles dominated by isoprene and monoterpenes, respectively. These results show that emissions of BVOCs are highly dependent on the plant cover supported by the varying soil moisture, suggesting that high arctic BVOC emissions may affect the climate differently if soil water content and plant cover change. PMID- 27552737 TI - Corrigendum to "What is the concentration of hydrogen peroxide in blood and plasma?" [Arch. Biochem. Biophys. 603 (2016) 48-53]. PMID- 27552738 TI - Identification of lipid metabolism-targeting compounds active against drug resistant M. tuberculosis. PMID- 27552740 TI - Aromaticity-Controlled Energy Storage Capacity of the Dihydroazulene Vinylheptafulvene Photochromic System. AB - Photochemical conversion of molecules into high-energy isomers that, after a stimulus, return to the original isomer presents a closed-cycle of light harvesting, energy storage, and release. One challenge is to achieve a sufficiently high energy storage capacity. Here, we present efforts to tune the dihydroazulene/vinylheptafulvene (DHA/VHF) couple through loss/gain of aromaticity. Two derivatives were prepared, one with aromatic stabilization of DHA and the second of VHF. The consequences for the switching properties were elucidated. For the first type, sigmatropic rearrangements of DHA occurred upon irradiation. Formation of a VHF complex could be induced by a Lewis acid, but addition of H2 O resulted in immediate regeneration of DHA. For the second type, the VHF was too stable to convert into DHA. Calculations support the results and provide new targets. We predict that by removing one of the two CN groups at C-1 of the aromatic DHA, the heat storage capacity will be further increased, as will the life-time of the VHF. Calculations also reveal that a CN group at the fulvene ring retards the back-reaction, and we show synthetically that it can be introduced regioselectively. PMID- 27552739 TI - Multidimensional solid-state NMR spectroscopy of plant cell walls. AB - Plant biomass has become an important source of bio-renewable energy in modern society. The molecular structure of plant cell walls is difficult to characterize by most atomic-resolution techniques due to the insoluble and disordered nature of the cell wall. Solid-state NMR (SSNMR) spectroscopy is uniquely suited for studying native hydrated plant cell walls at the molecular level with chemical resolution. Significant progress has been made in the last five years to elucidate the molecular structures and interactions of cellulose and matrix polysaccharides in plant cell walls. These studies have focused on primary cell walls of growing plants in both the dicotyledonous and grass families, as represented by the model plants Arabidopsis thaliana, Brachypodium distachyon, and Zea mays. To date, these SSNMR results have shown that 1) cellulose, hemicellulose, and pectins form a single network in the primary cell wall; 2) in dicot cell walls, the protein expansin targets the hemicellulose-enriched region of the cellulose microfibril for its wall-loosening function; and 3) primary wall cellulose has polymorphic structures that are distinct from the microbial cellulose structures. This article summarizes these key findings, and points out future directions of investigation to advance our fundamental understanding of plant cell wall structure and function. PMID- 27552743 TI - Noise Estimation and Reduction in Magnetic Resonance Imaging Using a New Multispectral Nonlocal Maximum-likelihood Filter. AB - Denoising of magnetic resonance (MR) images enhances diagnostic accuracy, the quality of image manipulations such as registration and segmentation, and parameter estimation. The first objective of this paper is to introduce a new, high-performance, nonlocal filter for noise reduction in MR image sets consisting of progressively-weighted, that is, multispectral, images. This filter is a multispectral extension of the nonlocal maximum likelihood filter (NLML). Performance was evaluated on synthetic and in-vivo T2 - and T1 -weighted brain imaging data, and compared to the nonlocal-means (NLM) and its multispectral version, that is, MS-NLM, and the nonlocal maximum likelihood (NLML) filters. Visual inspection of filtered images and quantitative analyses showed that all filters provided substantial reduction of noise. Further, as expected, the use of multispectral information improves filtering quality. In addition, numerical and experimental analyses indicated that the new multispectral NLML filter, MS-NLML, demonstrated markedly less blurring and loss of image detail than seen with the other filters evaluated. In addition, since noise standard deviation (SD) is an important parameter for all of these nonlocal filters, a multispectral extension of the method of maximum likelihood estimation (MLE) of noise amplitude is presented and compared to both local and nonlocal MLE methods. Numerical and experimental analyses indicated the superior performance of this multispectral method for estimation of noise SD. PMID- 27552744 TI - Compactly Supported Radial Basis Function-Based Meshless Method for Photon Propagation Model of Fluorescence Molecular Tomography. AB - Fluorescence Molecular Tomography (FMT) is a powerful imaging modality for the research of cancer diagnosis, disease treatment and drug discovery. Via three dimensional (3-D) imaging reconstruction, it can quantitatively and noninvasively obtain the distribution of fluorescent probes in biological tissues. Currently, photon propagation of FMT is conventionally described by the Finite Element Method (FEM), and it can obtain acceptable image quality. However, there are still some inherent inadequacies in FEM, such as time consuming, discretization error and inflexibility in mesh generation, which partly limit its imaging accuracy. To further improve the solving accuracy of photon propagation model (PPM), we propose a novel compactly supported radial basis functions (CSRBFs) based meshless method (MM) to implement the PPM of FMT. We introduced a series of independent nodes and continuous CSRBFs to interpolate the PPM, which can avoid complicated mesh generation. To analyze the performance of the proposed MM, we carried out numerical heterogeneous mouse simulation to validate the simulated surface fluorescent measurement. Then we performed an in vivo experiment to observe the tomographic reconstruction. The experimental results confirmed that our proposed MM could obtain more similar surface fluorescence measurement with the golden standard (Monte-Carlo method), and more accurate reconstruction result was achieved via MM in in vivo application. PMID- 27552745 TI - Kalman Filtered Bio Heat Transfer Model Based Self-adaptive Hybrid Magnetic Resonance Thermometry. AB - To develop a self-adaptive and fast thermometry method by combining the original hybrid magnetic resonance thermometry method and the bio heat transfer equation (BHTE) model. The proposed Kalman filtered Bio Heat Transfer Model Based Self adaptive Hybrid Magnetic Resonance Thermometry, abbreviated as KalBHT hybrid method, introduced the BHTE model to synthesize a window on the regularization term of the hybrid algorithm, which leads to a self-adaptive regularization both spatially and temporally with change of temperature. Further, to decrease the sensitivity to accuracy of the BHTE model, Kalman filter is utilized to update the window at each iteration time. To investigate the effect of the proposed model, computer heating simulation, phantom microwave heating experiment and dynamic in-vivo model validation of liver and thoracic tumor were conducted in this study. The heating simulation indicates that the KalBHT hybrid algorithm achieves more accurate results without adjusting lambda to a proper value in comparison to the hybrid algorithm. The results of the phantom heating experiment illustrate that the proposed model is able to follow temperature changes in the presence of motion and the temperature estimated also shows less noise in the background and surrounding the hot spot. The dynamic in-vivo model validation with heating simulation demonstrates that the proposed model has a higher convergence rate, more robustness to susceptibility problem surrounding the hot spot and more accuracy of temperature estimation. In the healthy liver experiment with heating simulation, the RMSE of the hot spot of the proposed model is reduced to about 50% compared to the RMSE of the original hybrid model and the convergence time becomes only about one fifth of the hybrid model. The proposed model is able to improve the accuracy of the original hybrid algorithm and accelerate the convergence rate of MR temperature estimation. PMID- 27552746 TI - Optimized Graph Learning Using Partial Tags and Multiple Features for Image and Video Annotation. AB - In multimedia annotation, due to the time constraints and the tediousness of manual tagging, it is quite common to utilize both tagged and untagged data to improve the performance of supervised learning when only limited tagged training data are available. This is often done by adding a geometry-based regularization term in the objective function of a supervised learning model. In this case, a similarity graph is indispensable to exploit the geometrical relationships among the training data points, and the graph construction scheme essentially determines the performance of these graph-based learning algorithms. However, most of the existing works construct the graph empirically and are usually based on a single feature without using the label information. In this paper, we propose a semi-supervised annotation approach by learning an optimized graph (OGL) from multi-cues (i.e., partial tags and multiple features), which can more accurately embed the relationships among the data points. Since OGL is a transductive method and cannot deal with novel data points, we further extend our model to address the out-of-sample issue. Extensive experiments on image and video annotation show the consistent superiority of OGL over the state-of-the-art methods. PMID- 27552747 TI - Structure Selective Depth Superresolution for RGB-D Cameras. AB - This paper describes a method for high-quality depth superresolution. The standard formulations of image-guided depth upsampling, using simple joint filtering or quadratic optimization, lead to texture copying and depth bleeding artifacts. These artifacts are caused by inherent discrepancy of structures in data from different sensors. Although there exists some correlation between depth and intensity discontinuities, they are different in distribution and formation. To tackle this problem, we formulate an optimization model using a nonconvex regularizer. A nonlocal affinity established in a high-dimensional feature space is used to offer precisely localized depth boundaries. We show that the proposed method iteratively handles differences in structure between depth and intensity images. This property enables reducing texture copying and depth bleeding artifacts significantly on a variety of range data sets. We also propose a fast alternating direction method of multipliers algorithm to solve our optimization problem. Our solver shows a noticeable speed up compared with the conventional majorize-minimize algorithm. Extensive experiments with synthetic and real-world data sets demonstrate that the proposed method is superior to the existing methods. PMID- 27552748 TI - Perceptually Motivated Image Features Using Contours. AB - Dong et al. examined the ability of 51 computational feature sets to estimate human perceptual texture similarity; however, none performed well for this task. While it is well-known that the human visual system is extremely adept at exploiting longer-range aperiodic (and periodic) "contour" characteristics in images, none of the investigated feature sets exploit higher order statistics (HOS) over larger image regions ( > 19*19 pixels). We, therefore, hypothesise that long-range HOS, in the form of contour data, are useful for perceptual texture similarity estimation. We present the results of a psychophysical experiment that shows that contour data are more important, than local image patches, or global second-order data, to human observers for this task. Inspired by this finding, we propose a set of perceptually motivated image features (PMIF) that encode the long-range HOS computed from spatial and angular distributions of contour segments. We use two perceptual texture similarity estimation tasks to compare PMIF against the 51 feature sets referred to above and four commonly used contour representations. This new feature set is also examined in the context of two additional tasks: sketch-based image retrieval and natural scene recognition. The results show that the proposed feature set performs better, or at least comparably to, all the other feature sets. We attribute this promising performance to the fact that the proposed feature set exploits both short-range and long-range HOS. PMID- 27552749 TI - CU Partition Mode Decision for HEVC Hardwired Intra Encoder Using Convolution Neural Network. AB - The intensive computation of High Efficiency Video Coding (HEVC) engenders challenges for the hardwired encoder in terms of the hardware overhead and the power dissipation. On the other hand, the constrains in hardwired encoder design seriously degrade the efficiency of software oriented fast coding unit (CU) partition mode decision algorithms. A fast algorithm is attributed as VLSI friendly, when it possesses the following properties. First, the maximum complexity of encoding a coding tree unit (CTU) could be reduced. Second, the parallelism of the hardwired encoder should not be deteriorated. Third, the process engine of the fast algorithm must be of low hardware- and power-overhead. In this paper, we devise the convolution neural network based fast algorithm to decrease no less than two CU partition modes in each CTU for full rate-distortion optimization (RDO) processing, thereby reducing the encoder's hardware complexity. As our algorithm does not depend on the correlations among CU depths or spatially nearby CUs, it is friendly to the parallel processing and does not deteriorate the rhythm of RDO pipelining. Experiments illustrated that, an averaged 61.1% intraencoding time was saved, whereas the Bjontegaard-Delta bit rate augment is 2.67%. Capitalizing on the optimal arithmetic representation, we developed the high-speed [714 MHz in the worst conditions (125 degrees C, 0.9 V)] and low-cost (42.5k gate) accelerator for our fast algorithm by using TSMC 65 nm CMOS technology. One accelerator could support HD1080p at 55 frames/s real time encoding. The corresponding power dissipation was 16.2 mW at 714 MHz. Finally, our accelerator is provided with good scalability. Four accelerators fulfill the throughput requirements of UltraHD-4K at 55 frames/s. PMID- 27552750 TI - Automatic Registration of Wide Area Motion Imagery to Vector Road Maps by Exploiting Vehicle Detections. AB - To enrich large-scale visual analytics applications enabled by aerial wide area motion imagery (WAMI), we propose a novel methodology for accurately registering a geo-referenced vector roadmap to WAMI by using the locations of detected vehicles and determining a parametric transform that aligns these locations with the network of roads in the roadmap. Specifically, the problem is formulated in a probabilistic framework, explicitly allowing for spurious detections that do not correspond to on-road vehicles. The registration is estimated via the expectation maximization (EM) algorithm as the planar homography that minimizes the sum of weighted squared distances between the homography-mapped detection locations and the corresponding closest point on the road network, where the weights are estimated posterior probabilities of detections being on-road vehicles. The weighted distance minimization is efficiently performed using the distance transform with the Levenberg-Marquardt nonlinear least-squares minimization procedure, and the fraction of spurious detections is estimated within the EM framework. The proposed method effectively sidesteps the challenges of feature correspondence estimation, applies directly to different imaging modalities, is robust to spurious detections, and is also more appropriate than feature matching for a planar homography. Results over three WAMI data sets captured by both visual and infrared sensors indicate the effectiveness of the proposed methodology: both visual comparison and numerical metrics for the registration accuracy are significantly better for the proposed method as compared with the existing alternatives. PMID- 27552751 TI - Universal Demosaicking of Color Filter Arrays. AB - A large number of color filter arrays (CFAs), periodic or aperiodic, have been proposed. To reconstruct images from all different CFAs and compare their imaging quality, a universal demosaicking method is needed. This paper proposes a new universal demosaicking method based on inter-pixel chrominance capture and optimal demosaicking transformation. It skips the commonly used step to estimate the luminance component at each pixel, and thus, avoids the associated estimation error. Instead, we directly use the acquired CFA color intensity at each pixel as an input component. Two independent chrominance components are estimated at each pixel based on the inter-pixel chrominance in the window, which is captured with the difference of CFA color values between the pixel of interest and its neighbors. Two mechanisms are employed for the accurate estimation: distance related and edge-sensing weighting to reflect the confidence levels of the inter pixel chrominance components, and pseudoinverse-based estimation from the components in a window. Then from the acquired CFA color component and two estimated chrominance components, the three primary colors are reconstructed by a linear color transform, which is optimized for the least transform error. Our experiments show that the proposed method is much better than other published universal demosaicking methods. PMID- 27552752 TI - Motion Driven Tonal Stabilization. AB - This paper addresses the problem of tonal fluctuation in videos. Due to the automatic settings of consumer cameras, the colors of objects in image sequences might change over time. We propose here a fast and computationally light method to stabilize this tonal appearance, while remaining robust to motion and occlusions. To do so, a minimally viable color correction model is used, in conjunction with an effective estimation of dominant motion. The final solution is a temporally weighted correction, explicitly driven by the motion magnitude, both visually efficient and very fast, with potential to real time processing. Experimental results obtained on a variety of sequences outperform the current state of the art in terms of tonal stability, at a much reduced computational complexity. PMID- 27552753 TI - Beyond the Sparsity-Based Target Detector: A Hybrid Sparsity and Statistics-Based Detector for Hyperspectral Images. AB - Hyperspectral images provide great potential for target detection, however, new challenges are also introduced for hyperspectral target detection, resulting that hyperspectral target detection should be treated as a new problem and modeled differently. Many classical detectors are proposed based on the linear mixing model and the sparsity model. However, the former type of model cannot deal well with spectral variability in limited endmembers, and the latter type of model usually treats the target detection as a simple classification problem and pays less attention to the low target probability. In this case, can we find an efficient way to utilize both the high-dimension features behind hyperspectral images and the limited target information to extract small targets? This paper proposes a novel sparsity-based detector named the hybrid sparsity and statistics detector (HSSD) for target detection in hyperspectral imagery, which can effectively deal with the above two problems. The proposed algorithm designs a hypothesis-specific dictionary based on the prior hypotheses for the test pixel, which can avoid the imbalanced number of training samples for a class-specific dictionary. Then, a purification process is employed for the background training samples in order to construct an effective competition between the two hypotheses. Next, a sparse representation-based binary hypothesis model merged with additive Gaussian noise is proposed to represent the image. Finally, a generalized likelihood ratio test is performed to obtain a more robust detection decision than the reconstruction residual-based detection methods. Extensive experimental results with three hyperspectral data sets confirm that the proposed HSSD algorithm clearly outperforms the state-of-the-art target detectors. PMID- 27552754 TI - Incorporating Spatial Information and Endmember Variability Into Unmixing Analyses to Improve Abundance Estimates. AB - Incorporating endmember variability and spatial information into spectral unmixing analyses is important for producing accurate abundance estimates. However, most methods do not incorporate endmember variability with spatial regularization. This paper proposes a novel 2-step unmixing approach, which incorporates endmember variability and spatial information. In step 1, a probability distribution representing abundances is estimated by spectral unmixing within a multi-task Gaussian process framework (SUGP). In step 2, spatial information is incorporated into the probability distribution derived by SUGP through an a priori distribution derived from a Markov random field (MRF). The proposed method (SUGP-MRF) is different to the existing unmixing methods because it incorporates endmember variability and spatial information at separate steps in the analysis and automatically estimates parameters controlling the balance between the data fit and spatial smoothness. The performance of SUGP-MRF is compared with the existing unmixing methods using synthetic imagery with precisely known abundances and real hyperspectral imagery of rock samples. Results show that SUGP-MRF outperforms the existing methods and improves the accuracy of abundance estimates by incorporating spatial information. PMID- 27552755 TI - Compressive Estimation and Imaging Based on Autoregressive Models. AB - Compressed sensing (CS) is a fast and efficient way to obtain compact signal representations. Oftentimes, one wishes to extract some information from the available compressed signal. Since CS signal recovery is typically expensive from a computational point of view, it is inconvenient to first recover the signal and then extract the information. A much more effective approach consists in estimating the information directly from the signal's linear measurements. In this paper, we propose a novel framework for compressive estimation of autoregressive (AR) process parameters based on ad hoc sensing matrix construction. More in detail, we introduce a compressive least square estimator for AR(p) parameters and a specific AR(1) compressive Bayesian estimator. We exploit the proposed techniques to address two important practical problems. The first is compressive covariance estimation for Toeplitz structured covariance matrices where we tackle the problem with a novel parametric approach based on the estimated AR parameters. The second is a block-based compressive imaging system, where we introduce an algorithm that adaptively calculates the number of measurements to be acquired for each block from a set of initial measurements based on its degree of compressibility. We show that the proposed techniques outperform the state-of-the-art methods for these two problems. PMID- 27552756 TI - Regularization Parameter Estimation for Non-Negative Hyperspectral Image Deconvolution. AB - This paper aims at studying a method to automatically estimate the regularization parameters of non-negative hyperspectral image deconvolution methods. The deconvolution problem is formulated as a multi-objective optimization problem and the properties of the corresponding response surface are studied. Based on these properties, the minimum distance criterion (MDC) and the maximum curvature criterion (MCC) are proposed to estimate regularization parameters especially for the non-negativity constrained deconvolution problem. MDC has good theoretical properties (convexity and uniqueness) but requires to choose a reference point. On the contrary, MCC does not need to choose any reference point but does not have interesting theoretical properties. A grid-search-based approach to minimize the computational cost of MDC and MCC is proposed. It results in fast approaches to estimate the regularization parameters. Based on simulated 2D images, the proposed approaches are compared with the state-of-the-art methods, confirming the effectiveness of the MDC and MCC for the non-negativity constrained image deconvolution problem. In the case of non-negative hyperpsectral image deconvolution, the fast MDC yields better performances than the fast MCC. An application to real-world hyperspectral fluorescence microscopy images is also provided; it confirms the superiority of MDC. PMID- 27552757 TI - A Coupled Hidden Conditional Random Field Model for Simultaneous Face Clustering and Naming in Videos. AB - For face naming in TV series or movies, a typical way is using subtitles/script alignment to get the time stamps of the names, and tagging them to the faces. We study the problem of face naming in videos when subtitles are not available. To this end, we divide the problem into two tasks: face clustering which groups the faces depicting a certain person into a cluster, and name assignment which associates a name to each face. Each task is formulated as a structured prediction problem and modeled by a hidden conditional random field (HCRF) model. We argue that the two tasks are correlated problems whose outputs can provide prior knowledge of the target prediction for each other. The two HCRFs are coupled in a unified graphical model called coupled HCRF where the joint dependence of the cluster labels and face name association is naturally embedded in the correlation between the two HCRFs. We provide an effective algorithm to optimize the two HCRFs iteratively and the performance of the two tasks on real world data set can be both improved. PMID- 27552758 TI - Context-Aware Surveillance Video Summarization. AB - We present a method that is able to find the most informative video portions, leading to a summarization of video sequences. In contrast to the existing works, our method is able to capture the important video portions through information about individual local motion regions, as well as the interactions between these motion regions. Specifically, our proposed Context-Aware Video Summarization (CAVS) framework adopts the methodology of sparse coding with generalized sparse group lasso to learn a dictionary of video features and a dictionary of spatio temporal feature correlation graphs. Sparsity ensures that the most informative features and relationships are retained. The feature correlations, represented by a dictionary of graphs, indicate how motion regions correlate to each other globally. When a new video segment is processed by CAVS, both dictionaries are updated in an online fashion. Specifically, CAVS scans through every video segment to determine if the new features along with the feature correlations, can be sparsely represented by the learned dictionaries. If not, the dictionaries are updated, and the corresponding video segments are incorporated into the summarized video. The results on four public datasets, mostly composed of surveillance videos and a small amount of other online videos, show the effectiveness of our proposed method. PMID- 27552759 TI - Comparison-Based Image Quality Assessment for Selecting Image Restoration Parameters. AB - Image quality assessment (IQA) is traditionally classified into full-reference (FR) IQA, reduced-reference (RR) IQA, and no-reference (NR) IQA according to the amount of information required from the original image. Although NR-IQA and RR IQA are widely used in practical applications, room for improvement still remains because of the lack of the reference image. Inspired by the fact that in many applications, such as parameter selection for image restoration algorithms, a series of distorted images are available, the authors propose a novel comparison based IQA (C-IQA) framework. The new comparison-based framework parallels FR-IQA by requiring two input images and resembles NR-IQA by not using the original image. As a result, the new comparison-based approach has more application scenarios than FR-IQA does, and takes greater advantage of the accessible information than the traditional single-input NR-IQA does. Further, C-IQA is compared with other state-of-the-art NR-IQA methods and another RR-IQA method on two widely used IQA databases. Experimental results show that C-IQA outperforms the other methods for parameter selection, and the parameter trimming framework combined with C-IQA saves the computation of iterative image reconstruction up to 80%. PMID- 27552760 TI - Correspondence Driven Saliency Transfer. AB - In this paper, we show that large annotated data sets have great potential to provide strong priors for saliency estimation rather than merely serving for benchmark evaluations. To this end, we present a novel image saliency detection method called saliency transfer. Given an input image, we first retrieve a support set of best matches from the large database of saliency annotated images. Then, we assign the transitional saliency scores by warping the support set annotations onto the input image according to computed dense correspondences. To incorporate context, we employ two complementary correspondence strategies: a global matching scheme based on scene-level analysis and a local matching scheme based on patch-level inference. We then introduce two refinement measures to further refine the saliency maps and apply the random-walk-with-restart by exploring the global saliency structure to estimate the affinity between foreground and background assignments. Extensive experimental results on four publicly available benchmark data sets demonstrate that the proposed saliency algorithm consistently outperforms the current state-of-the-art methods. PMID- 27552763 TI - TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position Specific Nucleotide Propensities and a Support Vector Machine. AB - As one of the most ubiquitous post-transcriptional modifications of RNA, N6 methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A. PMID- 27552765 TI - Haptic Feedback Manipulation During Botulinum Toxin Injection Therapy for Focal Hand Dystonia Patients: A Possible New Assistive Strategy. AB - Abnormality of sensorimotor integration in the basal ganglia and cortex has been reported in the literature for patients with task-specific focal hand dystonia (FHD). In this study, we investigate the effect of manipulation of kinesthetic input in people living with writer's cramp disorder (a major form of FHD). For this purpose, severity of dystonia is studied for 11 participants while the symptoms of seven participants have been tracked during five sessions of assessment and Botulinum toxin injection (BoNT-A) therapy (one of the current suggested therapies for dystonia). BoNT-A therapy is delivered in the first and the third session. The goal is to analyze the effect of haptic manipulation as a potential assistive technique during BoNT-A therapy. The trial includes writing, hovering, and spiral/sinusoidal drawing subtasks. In each session, the subtasks are repeated twice when (a) a participant uses a normal pen, and (b) when the participant uses a robotics-assisted system (supporting the pen) which provides a compliant virtual writing surface and manipulates the kinesthetic sensory input. The results show (p-value using one-sample t-tests) that reducing the writing surface rigidity significantly decreases the severity of dystonia and results in better control of grip pressure (an indicator of dystonic cramping). It is also shown that (p-value based on paired-samples t-test) using the proposed haptic manipulation strategy, it is possible to augment the effectiveness of BoNT-A therapy. The outcome of this study is then used in the design of an actuated pen as a writing-assistance tool that can provide compliant haptic interaction during writing for FHD patients. PMID- 27552767 TI - A Squeezed Artificial Neural Network for the Symbolic Network Reliability Functions of Binary-State Networks. AB - Network reliability is an important index to the provision of useful information for decision support in the modern world. There is always a need to calculate symbolic network reliability functions (SNRFs) due to dynamic and rapid changes in network parameters. In this brief, the proposed squeezed artificial neural network (SqANN) approach uses the Monte Carlo simulation to estimate the corresponding reliability of a given designed matrix from the Box-Behnken design, and then the Taguchi method is implemented to find the appropriate number of neurons and activation functions of the hidden layer and the output layer in ANN to evaluate SNRFs. According to the experimental results of the benchmark networks, the comparison appears to support the superiority of the proposed SqANN method over the traditional ANN-based approach with at least 16.6% improvement in the median absolute deviation in the cost of extra 2 s on average for all experiments.Network reliability is an important index to the provision of useful information for decision support in the modern world. There is always a need to calculate symbolic network reliability functions (SNRFs) due to dynamic and rapid changes in network parameters. In this brief, the proposed squeezed artificial neural network (SqANN) approach uses the Monte Carlo simulation to estimate the corresponding reliability of a given designed matrix from the Box-Behnken design, and then the Taguchi method is implemented to find the appropriate number of neurons and activation functions of the hidden layer and the output layer in ANN to evaluate SNRFs. According to the experimental results of the benchmark networks, the comparison appears to support the superiority of the proposed SqANN method over the traditional ANN-based approach with at least 16.6% improvement in the median absolute deviation in the cost of extra 2 s on average for all experiments. PMID- 27552768 TI - Lower Bounds on the Proportion of Leaders Needed for Expected Consensus of 3-D Flocks. AB - This paper considers the consensus behavior of a spatially distributed 3-D dynamical network composed of heterogeneous agents: leaders and followers, in which the leaders have the preferred information about the destination, while the followers do not have. All followers move in a 3-D Euclidean space with a given speed and with their headings updated according to the average velocity of the corresponding neighbors. Compared with the 2-D model, a key point lies in how to analyze the dynamical behavior of a "linear" nonhomogeneous equation where the nonhomogeneous term strongly nonlinearly depends on the states of all agents. Using the network structure and the estimation of some characteristics for the initial states, we present a proper decaying rate for the nonhomogeneous term and then establish lower bounds on the ratio of the number of leaders to the number of followers that is needed for the expected consensus by considering two cases: 1) fixed speed and neighborhood radius and 2) variable speed and neighborhood radius with respect to the population size. Some simulation examples are given to justify the theoretical results.This paper considers the consensus behavior of a spatially distributed 3-D dynamical network composed of heterogeneous agents: leaders and followers, in which the leaders have the preferred information about the destination, while the followers do not have. All followers move in a 3-D Euclidean space with a given speed and with their headings updated according to the average velocity of the corresponding neighbors. Compared with the 2-D model, a key point lies in how to analyze the dynamical behavior of a "linear" nonhomogeneous equation where the nonhomogeneous term strongly nonlinearly depends on the states of all agents. Using the network structure and the estimation of some characteristics for the initial states, we present a proper decaying rate for the nonhomogeneous term and then establish lower bounds on the ratio of the number of leaders to the number of followers that is needed for the expected consensus by considering two cases: 1) fixed speed and neighborhood radius and 2) variable speed and neighborhood radius with respect to the population size. Some simulation examples are given to justify the theoretical results. PMID- 27552769 TI - Adaptive Neural Networks Decentralized FTC Design for Nonstrict-Feedback Nonlinear Interconnected Large-Scale Systems Against Actuator Faults. AB - The problem of active fault-tolerant control (FTC) is investigated for the large scale nonlinear systems in nonstrict-feedback form. The nonstrict-feedback nonlinear systems considered in this paper consist of unstructured uncertainties, unmeasured states, unknown interconnected terms, and actuator faults (e.g., bias fault and gain fault). A state observer is designed to solve the unmeasurable state problem. Neural networks (NNs) are used to identify the unknown lumped nonlinear functions so that the problems of unstructured uncertainties and unknown interconnected terms can be solved. By combining the adaptive backstepping design principle with the combination Nussbaum gain function property, a novel NN adaptive output-feedback FTC approach is developed. The proposed FTC controller can guarantee that all signals in all subsystems are bounded, and the tracking errors for each subsystem converge to a small neighborhood of zero. Finally, numerical results of practical examples are presented to further demonstrate the effectiveness of the proposed control strategy.The problem of active fault-tolerant control (FTC) is investigated for the large-scale nonlinear systems in nonstrict-feedback form. The nonstrict feedback nonlinear systems considered in this paper consist of unstructured uncertainties, unmeasured states, unknown interconnected terms, and actuator faults (e.g., bias fault and gain fault). A state observer is designed to solve the unmeasurable state problem. Neural networks (NNs) are used to identify the unknown lumped nonlinear functions so that the problems of unstructured uncertainties and unknown interconnected terms can be solved. By combining the adaptive backstepping design principle with the combination Nussbaum gain function property, a novel NN adaptive output-feedback FTC approach is developed. The proposed FTC controller can guarantee that all signals in all subsystems are bounded, and the tracking errors for each subsystem converge to a small neighborhood of zero. Finally, numerical results of practical examples are presented to further demonstrate the effectiveness of the proposed control strategy. PMID- 27552772 TI - Co-production of research topics and designs. PMID- 27552774 TI - Burden of disease, research funding and innovation in the UK: Do new health technologies reflect research inputs and need? AB - OBJECTIVES: New and emerging health technologies (innovation outputs) do not always reflect conditions representing the greatest disease burden. We examine the role of research and development (R&D) funding in this relationship, considering whether areas with fewer innovative outputs receive an appropriate share of funding relative to their disease burden. METHODS: We report a retrospective observational study, comparing burden of disease with R&D funding and innovation output. UK disability-adjusted life years (DALYs) and deaths came from the World Health Organization (WHO) 2004 Global Burden of Disease estimates; funding estimates from the UK Clinical Research Collaboration's 2006 Health Research Analysis; and innovation output was estimated by the number of new and emerging technologies reported by the National Institute for Health Research (NIHR) Horizon Scanning Centre between 2000 and 2009. RESULTS: Disease areas representing the biggest burden were generally associated with the most funding and innovation output; cancer, neuropsychiatric conditions and cardiovascular disease together comprised approximately two-thirds of DALYs, funding and reported technologies. Compared with DALYs, funding and technologies were disproportionately high for cancer, and technologies alone were disproportionately high for musculoskeletal conditions and endocrine/metabolic diseases. Neuropsychiatric conditions had comparatively few technologies compared to both DALYs and funding. The relationship between DALYs and innovation output appeared to be mediated by R&D funding. CONCLUSIONS: The relationship between burden of disease and new and emerging health technologies for different disease areas is partly dependent on the associated level of R&D funding (input). Discrepancies among key groups may reflect differential focus of research funding across disease areas. PMID- 27552773 TI - Behaviour change among people with impaired glucose tolerance: Comparison of telephone-based and face-to-face advice. AB - OBJECTIVES: To develop, implement and compare two lifestyle services for people at risk of developing type 2 diabetes. METHODS: Two localities were selected to implement two different service delivery models, telephone-based and face-to face, supporting people at risk of developing type 2 diabetes. Impact was assessed by comparing weight, fasting plasma glucose and oral glucose tolerance test (OGTT) results at baseline and six months later. RESULTS: Both services were associated with an improvement in OGTT 2-h plasma glucose and weight. In the telephone intervention, 47.3% of participants who completed the project achieved both normal fasting plasma glucose (<=6.0 mmol/l) and normal plasma glucose levels (<=7.7 mmol/l). Participants had a mean weight loss of 3.3 kg (SD 4.3), equating to 3.4% of body weight (p < 0.001). In the face-to-face intervention, 46.3% of participants achieved normal plasma glucose (<=7.7 mmol/l) and a mean weight loss of 2.9 kg (SD 4.5), equating to 3.1% of bodyweight (p < 0.001). CONCLUSIONS: Local health providers can adapt existing service provision and tailor it to provide lifestyle programmes for people with impaired glucose tolerance. Both service delivery models offer effective diabetes prevention although each model may cater for different population needs and a choice of services might be the preferred option. PMID- 27552775 TI - How organizational factors interact to influence the quality of care of older people in the care home sector. AB - OBJECTIVES: To examine how organizational factors affect good care and mistreatment of older people in care homes. METHODS: Eight residential care homes for older people (including private sector, local authority and NHS providers) took part in a participatory observation-based study of organizational factors affecting care quality. RESULTS: Grouping organizational factors into infrastructure, management and procedures, staffing, resident population characteristics and culture, we show the context-sensitive nature of interactions between these factors. These interactions could enhance care quality where factors combined positively. Conversely, they could amplify difficulties where one factor came to undermine another, thereby limiting care quality. CONCLUSIONS: This analysis provides empirical insights into how and why similar sector-wide changes to care provision have differential effects at the care home level. It indicates the situated and unpredictable ways in which organizational factors interact, implying the need for locally contextualized quality assessment and improvement actions. PMID- 27552776 TI - Developing engagement, linkage and exchange between health services managers and researchers: Experience from the UK. AB - OBJECTIVES: The UK National Institute for Health Research (NIHR) Service Delivery and Organisation (SDO) Management Fellowship programme enabled health services managers and university researchers to collaborate on research projects with the aim of improving research, managers' research knowledge and skills, and the use of research in management. Our aim was to evaluate whether the programme encouraged greater engagement, linkage and exchange between researchers and managers. METHODS: A case-study approach with each case-study centred on 11 health care managers appointed as Fellows, chief investigators (n = 13) and Fellows' line managers (n = 12). Data were collected through semi-structured face to-face and telephone interviews. Interviews were analysed thematically to explore the impact of the programme, reported issues and to identify any lessons learned. RESULTS: Researchers benefited from the flow of (insider) knowledge and contacts from the workplace via the Fellow to the project. Engagement, linkage and exchange as a result of the Fellowship were less developed for the workplace. Reasons for this related to the fit of the research project with workplace interests, Fellows' contact with the health care organization, feedback structures and training. The potential for co-production of knowledge was under developed. A transactional notion of exchange was found in operation in workplaces. CONCLUSIONS: The programme's aim to enhance engagement, linkage and exchange was largely achieved, although exchange tended to be narrowly conceived. Knowing how models of exchange work in practice can ensure effort is put to best use. PMID- 27552777 TI - Commissioning vocational rehabilitation after stroke: Can the Cinderella services get to the ball? A qualitative study. AB - OBJECTIVE: To understand the barriers and enablers to commissioning vocational rehabilitation (VR) after stroke. METHODS: Interviews with health and social care commissioners responsible for stroke services across three counties were conducted to explore their views on the barriers and enablers to commissioning VR. Transcripts were subjected to thematic analysis, and validity checked with members of the research team. RESULTS: The findings indicate that health commissioners have had to focus on demand-led and expensive acute stroke services, leaving little resource for community services. Though the benefits of VR to patient health are acknowledged, any cost savings would not be realized within the health budget. Social care commissioners, in times of budget restriction, focus on the most vulnerable, aiming to maintain independence and reduce care home admission. In the absence of evidence, there is a perception that the need for VR after stroke is relatively minor. CONCLUSIONS: Factors which might facilitate commissioning of a VR service include adapting the service to align with commissioners' requirements, making VR a targeted outcome of community stroke services, utilizing emerging opportunities for joint health and social care commissioning such as Health and Wellbeing Boards, and closer working with researchers to improve the evidence-base. PMID- 27552778 TI - Is a larger specialist nurse workforce in cancer care associated with better patient experience? Cross-sectional study. AB - OBJECTIVES: To assess whether variation in the provision of cancer specialist nurses is associated with the experiences of care for patients undergoing treatment for cancer. METHODS: This is a cross-sectional study using routinely collected national survey data in 158 acute hospital National Health Service (NHS) Trusts in England. Patients with a primary diagnosis of cancer who attended hospital as inpatients or day cases in the first three months of 2010 responded to a national survey (n = 67,713, response rate 67%). Patient perceptions of coordination of care, quality of information provision, emotional support and support for symptom management were studied. RESULTS: Patients in Trusts that had the fewest patients per specialist nurse were more likely to report that people treating and caring for them worked well together (adjusted odds ratio 1.08, 95% confidence interval 1.01-1.15; p = 0.02) and provided enough emotional support during ambulatory treatment (1.15, 1.01-1.32; p = 0.04), but were no more likely to report being given the right amount of information (0.96, 0.88-1.05; p = 0.38) when compared to patients in Trusts with the most patients per specialist nurse. Breast cancer patients undergoing chemotherapy in the Trusts with fewer patients per specialist nurse were more likely to report good support for the control of side effects from chemotherapy (1.34, 1.02-1.75; p = 0.03). CONCLUSIONS: Cancer patients' experience of care coordination and emotional support was better in Trusts with more specialist nurses. The absolute differences were small, and it was unclear whether particular roles or service configurations are associated with better experience. PMID- 27552779 TI - Stimulating whole system redesign: Lessons from an organizational analysis of the Whole System Demonstrator programme. AB - OBJECTIVES: Whole system integration of health and social care has been positioned as key to improving care, increasing efficiency and controlling costs. However, evidence for the benefits of whole system integration is scarce. Drawing on organizational theory, this study uses the implementation of remote care services, viewed as an enabler for whole system working, to explore the reality of achieving this policy objective. METHODS: Qualitative, longitudinal data were collected across nine UK sites adopting remote care over three years. Three sites formed the Department of Health's Whole Systems Demonstrator (WSD) programme for remote care. In addition, the implementation of remote care was explored in six other sites unconstrained by the randomized control trial procedures of the WSD programme. The methods were ethnographic (including 235 hours of observations and 184 interviews). Participants were health and social care staff and Government policy makers. RESULTS: Remote care did not lead to system redesign; however, local 'ownership' of new services did lead to more collaborative practices across the care system. Lack of integration was an enduring and endemic challenge across all sites, relating to differences in statutory responsibilities, absence of shared budgets and hybrid organizational roles, differences in work practices and organizational philosophies, and ambiguity around what 'whole system working' actually entailed. CONCLUSIONS: Policy initiatives like the WSD programme provide opportunities to phase in collaborative practices and create an awareness of the need for joint working. However, the progress observed suggests that the concept of whole system redesign around remote care is currently unrealistic. PMID- 27552780 TI - Effects of text messaging in addition to emails on physical activity among university and college employees in the UK. AB - OBJECTIVES: To test the effects of adding text messages to weekly email communications on recipients' total physical activity (leisure-time; workplace; domestic and garden; and active transportation) in employees of universities and colleges in the UK. METHODS: A randomised trial with two study groups (email only or email plus text messaging for 12 weeks) was implemented at five workplaces. Data were collected at baseline, immediately after, and four weeks after the intervention. Intervention effects on physical activity were evaluated using latent growth modelling. RESULTS: Total physical activity decreased over time in both groups but the decrease was non-significant. The only significant difference between groups was found for workplace physical activity, with the group receiving emails and text messages having a linear decrease of 2.81 Metabolic Equivalent h/week (beta = -0.31, p = 0.035) compared to the email only group. CONCLUSIONS: Sending employees two additional text messages resulted in less physical activity. Further investigation is needed to understand whether text messaging may play a beneficial role in promoting physical activity in workplace settings. PMID- 27552781 TI - Bagpipe lung; a new type of interstitial lung disease? PMID- 27552782 TI - Incidence and recognition of acute respiratory distress syndrome in a UK intensive care unit. AB - The reported incidence of ARDS is highly variable (2.5%-19% of intensive care unit (ICU) patients) and varies depending on study patient population used. We undertook a 6-month, prospective study to determine the incidence and outcome of ARDS in a UK adult University Hospital ICU. 344 patients were admitted during the study period, of these 43 (12.5%) were determined to have ARDS. Patients with ARDS had increased mortality at 28 days and 2 years post-diagnosis, and there was under-recognition of ARDS in both medical records and death certificattion. Our findings have implications for critical care resource planning. PMID- 27552783 TI - The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology. AB - Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms. PMID- 27552785 TI - Multiplex PCR Assay for Identifi cation and Differentiation of Campylobacter jejuni and Campylobacter coli Isolates. AB - INTRODUCTION: Campylobacter spp. are important causative agents of gastrointestinal infections in humans. The most frequently isolated strains of this bacterial genus are Campylobacter jejuni and Campylobacter coli. To date, genetic methods for bacterial identification have not been used in Bulgaria. We optimized the multiplex PSR assay to identify Campylobacter spp. and differentiate C. jejuni from C. coli in clinical isolates. We also compared this method with the routinely used biochemical methods. AIM: To identify Campylobacter spp. and discriminate C. coli from C. jejuni in clinical isolates using multiplex PCR assay. MATERIALS AND METHODS: Between February 2014 and January 2015 we studied 93 stool samples taken from patients with diarrheal syndrome and identified 40 species of Campylobacter spp. in them. The clinical material was cultured in microaerophilic atmosphere, the isolated strains being biochemically diff erentiated (hydrolysis of sodium hippurate for C. jejuni, and hydrolysis of indoxyl acetate for C. coli). DNA was isolated from the strains using QiaAmp MiniKit (QIAGEN, Germany). Twenty strains were tested with multiplex PCR for the presence of these genes: cadF, characteristic for Campylobacter spp., hipO for C. jejuni and asp for C. coli. RESULTS AND DISCUSSION: The biochemical tests identified 16 strains of C. jejuni, 3 strains of C. coli, and 1 strain of C. upsaliensis. After the multiplex PCR assay the capillary gel electrophoresis confirmed 16 strains of C. jejuni, 2 strains of C. coli and 2 strains of Campylobacter spp. - because of the presence of the gene cadF. C. jejuni has the gene hipO, and it is possible that this gene may not be expressed in the biochemical differentiation yielding a negative reaction as a result. In comparison, we can conclude that the genetic differentiation is a more accurate method than the biochemical tests. CONCLUSION: The multiplex PCR assay is a fast, accurate method for identifi cation of Campylobacter spp. which makes it quite necessary in the clinical diagnostic practice. PMID- 27552784 TI - Changes in Hematologic and Coagulation Profiles in Rabbits with Right-ventricle Pacing. AB - OBJECTIVES: The aim of this study was to evaluate changes in hematology and coagulation in rabbits with right-ventricle pacing without medication. ANIMALS AND METHODS: Blood was collected from ten non-anesthetized male rabbits from the jugular vein before and one month after pacemaker placement. Total erythrocyte, leukocyte and platelet count, hemoglobin, hematocrit and differential leukocyte count were done on automatic veterinary flow cytometry hematologic analyzer. Prothrombin time, activated partial thromboplastin time, fibrinogen level, D dimers and kaolin-activated thromboelastography was measured from citrated blood. RESULTS: We found an increase in red blood cell mass and decrease in platelet count, while coagulation tests did not diff er between samplings. CONCLUSION: Right-ventricle pacing seems to have no influence on hemostasis in rabbits. PMID- 27552786 TI - Minimal Invasive Approach for Lips Venous Lake Treatment by 980 nm Diode Laser with Emphasis on the Aesthetic Results. A Clinical Series. AB - INTRODUCTION: A venous lake (VL) is a vascular lesion with common occurrence in many patients, manifested as a dark blue-to-violet compressible papule, caused by dilation of venules. The main reasons for the treatment of VL are aesthetic. The haemorrhaging episodes or impairment of oral normal functions are also under considerations. Treatment of lip VL includes surgical excision, selective photocoagulation, cryotherapy, sclerotherapy and electrodessication. The high intensity diode laser is an option. The 980 nm diode laser is selectively absorbed by haemoglobin and selectively destroys blood vessels, minimising injury to the surrounding healthy skin. AIM: The purpose of this study was to evaluate the effectiveness of diode laser in the treatment of VL lesions with the accent on the postoperative defects and aesthetic results. METHODS: 35 patients aged 37 to 71 were included in this study. A 980 nm diode laser was used in noncontact mode, under local anaesthesia in continuous wave (2-3W, for 20-60s). All patients received only one procedure. RESULTS: Healing process was completed within 2 to 4 weeks after treatment with no scarring. None of the typical adverse effects were observed in the process of healing. CONCLUSIONS: Selective photocoagulation is an effective method for treatment of VL. Lower morbidity, minimal patient discomfort and satisfactory functional and aesthetic results are favourable for patients. To optimise the results and to reduce the adverse effects, basic knowledge on lasers and laser-tissue interactions is requisite. PMID- 27552787 TI - Vulvovaginal Candidiasis in Pregnant Women and its Importance for Candida Colonization of Newborns. AB - Vulvovaginal candidiasis is the second most common cause of vaginitis worldwide (after bacterial candidiasis). Maternal vulvovaginal candidiasis is a major risk factor for Candida colonization and infection of the infant where prognosis depends on different predisposing factors. The aim of this study was to determine the incidence and the etiological structure of vulvovaginal candidiasis in pregnant women and its impact on Candida colonization of newborns. MATERIALS AND METHODS: Samples of vaginal secretions from 80 healthy pregnant women who were clinically suspicious for Candida vaginitis were collected within 48 hours before delivery. Samples for probable Candida colonization from the oral mucosa and feces were collected from their newborns within 47-72 hours after birth. Samples were plated on Sabouraud agar, followed by species identification by API Candida yeast assay. RESULTS: Twenty-three (28.75 +/- 5.06%) of the evaluated pregnant women were positive for Candida spp. Positive samples for Candida colonization were found in 18 (22.22 +/- 4.62%) of the examined 81 newborns (one pair of twins) from mothers who were clinically suspicious for vaginal candidiasis. Isolates of the newborns were 100% identical to those of the mothers' vaginal secretion. Candida albicans was the predominant species identified in the pregnant women (91.67 +/- 0.06%) and in the neonates (83.33+/-8.78%). PMID- 27552788 TI - Chronic Treatment with Opiate Agonists in Bulgaria - Assessing the Quality of Life Using SF 36 v. 2. AB - INTRODUCTION: Drug addictions to psychoactive substances are disorders with a complex bio-psycho-social genesis, which are characterized with chronic relapses. Substance addiction causes multifactorial damage to the normal functioning of individuals and requires a multicenter approach for the treatment process. AIM: The aim of the study was to assess the quality of life of patients undergoing chronic treatment with the opiate agonist methadone using a standardized questionnaire method in Bulgarian. MATERIAL AND METHODS: The study included patients aged 18 to 40 years undergoing chronic treatment with methadone for at least six months. The study included 100 subjects. Seventy-six patients were from 5 clinical programs in Bulgaria; twenty- four clinically healthy age-matched subjects with no history of drug abuse, psychiatric and somatic diseases were the control group. RESULTS: We found significant differences between patients and controls in all components of the survey (P<0.05). The patients had lower scores than the control group in the SF-36 in terms of all eight components and both the physical and mental component summaries of the SF-36-survey. Patients compared between the groups by dose, duration of treatment with methadone and period of heroin abuse before initiating treatment did not show significant differences. There were no significant differences between patients with and without hepatitis C virus. CONCLUSIONS: Opiate addiction is a state associated with poor quality of life. The duration of treatment, the methadone dose, period of heroin abuse before initiating treatment and illness of hepatitis C virus does not correlate with lower results. PMID- 27552789 TI - The T-SCAN System in Evaluating Occlusal Contacts. AB - BACKGROUND: Normal occlusal and articulation relations between the jaws ensure equal distribution of occlusal forces during mastication. A T-SCAN system allows these relations to be measured dynamically during the articulation cycle. AIM: To evaluate the T-SCAN III system in measuring and assessing the forces of occlusal contacts and their digital presentation. PATIENTS AND METHODS: Thirty students aged 19 - 22 years were examined. Of these only one matched the study criteria: - intact dentition; - without or with class I fillings in teeth 36 or 46; - Angle's class I jaw relation We used a computerized occlusal analysis system T-SCAN in the study. It comes with a registering sensor for the occlusal contacts, a module for transmitting the signals to a computer, and conversion software to generate images on a computer screen. RESULTS: We evaluated the system's capabilities in registering the occlusal contacts during mastication on an occlusion film and the occlusal forces using a digital display. CONCLUSION: The T-SCAN system provides the only accurate way to determine and evaluate the time sequence and force of occlusal contacts by converting the qualitative data into quantitative and displaying them digitally. PMID- 27552790 TI - Mycobacterium avium Auricular Infection in an Apparent Immunocompetent Patient: A Case Report. AB - INTRODUCTION: Soft tissue infections with Mycobacterium avium complex are more likely to appear in immunocompromised patients. However, they may rarely arise in non-immunosuppressed individuals. AIM: To present the case of an ear infection with Mycobacterium avium in the absence of demonstrable immunosuppression. CASE REPORT: Clinical case description, blood tests, routine histology and tissue cultures. DISCUSSION: A female, apparent immunocompetent patient presented with a 6-month reddish, oedematous and painless lesion with fine scaling in the right ear. Histology showed numerous granulomas, composed of epithelioid histiocytes without central necrosis. Cultures grew Mycobacterium avium. An unusual accidental ear injury was the portal of microbial entry. The patient's lesion fully regressed after a 9-month course of antibiotics. CONCLUSION: Although M. avium infections are rare in immunocompetent patients, the possibility of such infections should be considered even in these subjects, when relevant clinical features and exposure to risk factors are present. PMID- 27552791 TI - Pulmonary exacerbation due to colistin-resistant Stenotrophomonas maltophilia in a Bulgarian cystic fibrosis patient. AB - In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. As Pseudomonas aeruginosa is the dominant pathogen in CF patients it has been the major target of all treatment strategies, possible antibiotic regimens and recommendations for years. More sophisticated antibiotic therapies introduced over the last decades have helped to improve the prognosis in cystic fibrosis, but then new multidrug-resistant pathogens emerged. We present a case of cystic fibrosis in a 16-year-old boy with pulmonary exacerbation due to colistin-resistant Stenotrophomonas maltophilia. This case raises some interesting questions regarding the antibiotic policy and treatment options in our country for patients with CF and multidrug-resistant strains. Colistin is used at present in Bulgaria as a strategic last option for the CF patients but with the advent of new more drug-resistant strains therapeutic approach should change - for instance, there should be restrictions imposed on the use of levofloxacin and trimethoprim/sulfamethoxazole which are regarded as "cheap and not so potent" antibiotics suitable for any infection and use them only in strict dependence on the respective culture results. PMID- 27552792 TI - Celiac Disease and Cystic Fibrosis: Challenges to Differential Diagnosis. AB - Cystic fibrosis and celiac disease were considered a single clinical entity for many years. Differentiation between the diseases occurred some time in the 1930s of the 20th Century. Both diseases may present the intestinal malabsorption syndrome and similar clinical manifestations that contribute to difficulties with clinical distinction. We describe a report of two patients with initial diagnosis of cystic fibrosis, who were subsequently diagnosed with celiac disease. These case reports emphasize the possibility of false positivity being shown in the sweat test in CD, which may result in delayed diagnosis and inadequate management of this disease. PMID- 27552794 TI - Does early introduction of foods protect against allergy? PMID- 27552793 TI - Dual energy CT with one full scan and a second sparse-view scan using structure preserving iterative reconstruction (SPIR). AB - Conventional dual-energy CT (DECT) reconstruction requires two full-size projection datasets with two different energy spectra. In this study, we propose an iterative algorithm to enable a new data acquisition scheme which requires one full scan and a second sparse-view scan for potential reduction in imaging dose and engineering cost of DECT. A bilateral filter is calculated as a similarity matrix from the first full-scan CT image to quantify the similarity between any two pixels, which is assumed unchanged on a second CT image since DECT scans are performed on the same object. The second CT image from reduced projections is reconstructed by an iterative algorithm which updates the image by minimizing the total variation of the difference between the image and its filtered image by the similarity matrix under data fidelity constraint. As the redundant structural information of the two CT images is contained in the similarity matrix for CT reconstruction, we refer to the algorithm as structure preserving iterative reconstruction (SPIR). The proposed method is evaluated on both digital and physical phantoms, and is compared with the filtered-backprojection (FBP) method, the conventional total-variation-regularization-based algorithm (TVR) and prior image-constrained-compressed-sensing (PICCS). SPIR with a second 10-view scan reduces the image noise STD by a factor of one order of magnitude with same spatial resolution as full-view FBP image. SPIR substantially improves over TVR on the reconstruction accuracy of a 10-view scan by decreasing the reconstruction error from 6.18% to 1.33%, and outperforms TVR at 50 and 20-view scans on spatial resolution with a higher frequency at the modulation transfer function value of 10% by an average factor of 4. Compared with the 20-view scan PICCS result, the SPIR image has 7 times lower noise STD with similar spatial resolution. The electron density map obtained from the SPIR-based DECT images with a second 10 view scan has an average error of less than 1%. PMID- 27552795 TI - Optimising the management of wheeze in preschool children. AB - One third of all preschool children will have an episode of wheeze and many of these present to primary care. Most will fall within a spectrum of diagnosis ranging from episodic viral wheeze to multiple trigger wheeze or early onset asthma. A small proportion will have other rare, but important, diagnoses such as foreign body aspiration, anaphylaxis, gastro-oesophageal reflux, congenital anatomical abnormalities or other chronic lung diseases. Clinical assessment should try to classify children into either episodic viral wheeze or multiple trigger wheeze phenotypes. In clinical practice children rarely fit neatly into either category and the phenotype may change overtime. Clinical examination may well be normal in a child presenting with chronic symptoms. Urgent outpatient review should be considered for symptoms present from early infancy, chronic wet cough, failure to thrive or systemic involvement. The child should be referred to hospital immediately if you suspect an inhaled foreign body or anaphylaxis (after administering IM adrenaline). NICE recommends immediate referral for children with wheeze and high-risk features and also those with intermediate-risk features failing to respond to bronchodilator therapy. Children with high-risk features on assessment should be treated immediately with inhaled bronchodilator therapy. Those with intermediate risk should be treated immediately with bronchodilator therapy and reassessed 15-30 minutes later. Intermediate-risk children who respond and low-risk children can be managed at home with bronchodilator therapy via a spacer device. PMID- 27552796 TI - Early intervention crucial in anxiety disorders in children. AB - Anxiety disorders are among the most common mental health disorders of childhood. Three quarters of anxiety disorders have their origins in childhood, with presentation often chronic in nature. Children with an anxiety disorder are 3.5 times more likely to experience depression or anxiety in adulthood, highlighting the importance of early diagnosis and appropriate treatment. Making a diagnosis can often prove difficult. It is important for clinicians to distinguish between normal anxiety and anxiety disorders. In the latter, symptoms may impair function and/or cause marked avoidance behaviour and significant distress. Younger children, who are less able to verbalise their anxiety, may show symptoms of regression of physical abilities (e.g. toileting, requiring carrying); increased attachment seeking behaviours (e.g. becoming more clingy); or increased physical symptoms (e.g. stomach aches). NICE quality standards recommend the need for an accurate assessment of which specific anxiety disorder the individual is experiencing, its severity, and the impact on functioning. NICE guidance for assessment of social anxiety disorder may be extrapolated to the assessment of other anxiety disorders: e.g. giving the child the opportunity to provide information on their own, and conducting a risk assessment. Where the child is experiencing significant distress or functional impairment (e.g. missing school, not taking part in age-appropriate activity), then specialist input is likely to be needed. PMID- 27552797 TI - Erectile dysfunction heralds onset of cardiovascular disease. AB - Erectile dysfunction (ED) was once assumed to be a psychological condition but has now been shown to share risk factors with cardiovascular disease including age, diabetes mellitus, smoking, hypertension and hypercholesterolaemia, suggesting an underlying vascular pathology. Evidence reveals that there is a potential link between ED and subsequent development of coronary artery disease. ED itself may also increase cardiovascular risk. The relative risk of developing coronary artery disease within ten years, in patients with moderate to severe ED, has been calculated as 14% in men aged 30-39 years and may be as high as 27% in those aged 60-69. The association appears greater when younger men presenting with ED are considered. The severity of ED has also been linked with the severity of coronary artery disease The proposed pathological mechanisms are based on a theory of endothelial dysfunction which eventually leads to atherosclerosis. This occurs first in more vulnerable narrow diameter vessels such as the cavernosal arteries. The artery size hypothesis may explain why ED occurs before manifestation of coronary artery disease. There is likely to be a delay between presentation with ED and clinical presentation with coronary artery disease. In one study, ED was found to present 39 months prior to coronary symptoms. This provides GPs with a valuable window of opportunity for risk assessment, subsequent primary prevention and early referral to a cardiologist. PMID- 27552798 TI - Sun damage. PMID- 27552799 TI - BLOOD-LETTING IN 1916. PMID- 27552800 TI - A little praise goes a long way. PMID- 27552801 TI - Cerebral perfusion monitoring in acute care surgery: current and perspective use. AB - INTRODUCTION: The technology near infrared spectroscopy (NIRS) has been utilized extensively in several clinical settings and one of which is in cerebral oximetry. This review will provide information on the technology, clinical applications and algorithm to follow when desaturation occurs. AREAS COVERED: The review will cover the technology of near infrared spectroscopy, cerebral oximetry and the utilization of cerebral oximetry in each clinical setting. Expert commentary: Cerebral oximetry provides a noninvasive measure of cerebral oxygenation, which when persistently declining, can serve as a warning sign of hemodynamic or metabolic compromise intraoperatively or a predictor of postoperative cognitive dysfunction. Although useful, the cerebral oximetry readings must be interpreted in the context of other clinical information. When cerebral desaturation is confirmed, an algorithm should be followed in an attempt to increase oxygen delivery to the brain and/or decrease cerebral metabolic rate of oxygen. PMID- 27552802 TI - Improving adherence to medication in adults with diabetes in the United Arab Emirates. AB - BACKGROUND: Diabetes is a chronic medical condition and adherence to medication in diabetes is important. Improving medication adherence in adults with diabetes would help prevent the chronic complications associated with diabetes. A case control trial was used to study the effects of an educational session on medication adherence among adults with diabetes as measured by the Morisky Medication adherence scale (MMAS-8(c)). METHODS: The study took place at the Dubai Police Health Centre between February 2015 and November 2015. Questionnaires were used to collect socio-demographic, clinical and disease related variables and the primary measure of outcome was adherence levels as measured by the Morisky Medication Adherence Scale (MMAS-8(c)). The intervention group involved a standardized thirty minute educational session focusing on the importance of adherence to medication. The change in MMAS-8(c) was measured at 6 months. RESULTS: Four hundred and forty six patients were enrolled. Mean age 61 year +/- 11. 48.4 % were male. The mean time since diagnosis of diabetes was 3.2 years (Range 1-15 years). At baseline two hundred and eighty eight (64.6 %) patients were considered non-adherent (MMAS-8(c) adherence score < 6) while 118 (26.5 %) and 40 (9.0 %) had low adherence (MMAS-8(c) adherence score < 6) and medium adherence (MMAS-8(c) adherence scores of 6 to 7) to their medication respectively. The percentage of patients scoring low adherence MMAS-8 scores in the interventional group dropped from 64.60 % at baseline to 44.80 % at 6-months (p = 0.01). There was no obvious change in the adherence scores at baseline and at 6-months in the control group. Based on the study data, the Wilcoxon signed rank test showed that at 6 months, the educational 30-min session on diabetes and adherence to medication did elicit a statistically significant change in adherence levels in adults with diabetes enrolled in the intervention arm (Z = 6.187, p <0.001). CONCLUSION: Adults with diabetes would benefit from educational sessions focusing on the importance of adherence to medication. Public health strategies should focus on wider educational strategies targeting medication adherence in diabetic patients in the UAE. PMID- 27552803 TI - Measurement of functional and morphodynamic neutrophil phenotypes in systemic inflammation and sepsis. PMID- 27552804 TI - Living apart together: crosstalk between the core and supernumerary genomes in a fungal plant pathogen. AB - BACKGROUND: Eukaryotes display remarkable genome plasticity, which can include supernumerary chromosomes that differ markedly from the core chromosomes. Despite the widespread occurrence of supernumerary chromosomes in fungi, their origin, relation to the core genome and the reason for their divergent characteristics are still largely unknown. The complexity of genome assembly due to the presence of repetitive DNA partially accounts for this. RESULTS: Here we use single molecule real-time (SMRT) sequencing to assemble the genome of a prominent fungal wheat pathogen, Fusarium poae, including at least one supernumerary chromosome. The core genome contains limited transposable elements (TEs) and no gene duplications, while the supernumerary genome holds up to 25 % TEs and multiple gene duplications. The core genome shows all hallmarks of repeat-induced point mutation (RIP), a defense mechanism against TEs, specific for fungi. The absence of RIP on the supernumerary genome accounts for the differences between the two (sub)genomes, and results in a functional crosstalk between them. The supernumerary genome is a reservoir for TEs that migrate to the core genome, and even large blocks of supernumerary sequence (>200 kb) have recently translocated to the core. Vice versa, the supernumerary genome acts as a refuge for genes that are duplicated from the core genome. CONCLUSIONS: For the first time, a mechanism was determined that explains the differences that exist between the core and supernumerary genome in fungi. Different biology rather than origin was shown to be responsible. A "living apart together" crosstalk exists between the core and supernumerary genome, accelerating chromosomal and organismal evolution. PMID- 27552806 TI - Integrating male sexual diversity into violence prevention efforts with men and boys: evidence from the Asia-Pacific Region. AB - Men's perpetration of gender-based violence remains a global public health issue. Violence prevention experts call for engagement of boys and men to change social norms around masculinity in order to prevent gender-based violence. Yet, men do not comprise a homogenous category. Drawing on probability estimates of men who report same-sex practices and preferences captured in a multi-country gender based violence prevention survey in the Asia-Pacific region, we test the effects of sexuality-related factors on men's adverse life experiences. We find that sexual minority men face statistically higher risk of lifetime adversity related to gender-based violence, stemming from gender inequitable norms in society. Sexuality is thus a key axis of differentiation among men in the Asia-Pacific region, influencing health and wellbeing and reflecting men's differential engagement with dominant norms of masculinity. Integrating awareness of male sexual diversity into gender-based violence prevention interventions, particularly those that work with boys and men, and bridging violence prevention programming between sexual minority communities and women, are essential to tackle the root drivers of violence. PMID- 27552805 TI - Evaluation of performance and impacts of maternal and child health hospital services using Data Envelopment Analysis in Guangxi Zhuang Autonomous Region, China: a comparison study among poverty and non-poverty county level hospitals. AB - BACKGROUND: As the core of the county-level Maternal and Child Health Hospitals (MCHH) in rural areas of China, the service efficiency affects the fairness and availability of healthcare services. This study aims to identify the determinants of hospital efficiency and explore how to improve the performance of MCHH in terms of productivity and efficiency. METHODS: Data was collected from a sample of 32 county-level MCHHs of Guangxi in 2014. Firstly, we specified and measured the indicators of the inputs and outputs which represent hospital resources expended and its profiles respectively. Then we estimated the efficiency scores using Data Envelopment Analysis (DEA) for each hospital. Efficiency scores were decomposed into technical, scale and congestion components, and the potential output increases and/or input reductions were also estimated in this model, which would make relatively inefficient hospitals more efficient. In the second stage, the estimated efficiency scores are regressed against hospital external and internal environment factors using a Tobit model. We used DEAP (V2.1) and R for data analysis. RESULTS: The average scores of technical efficiency, net technical efficiency (managerial efficiency) and scale efficiency of the hospitals were 0.875, 0.922 and 0.945, respectively. Half of the hospitals were efficient, and 9.4 % and 40.6 % were weakly efficient and inefficient, respectively. Among the low-productiveness hospitals, 61.1 % came from poor counties (Poor counties in this article are in the list of key poverty-stricken counties at the national level, published by The State Council Leading Group Office of Poverty Alleviation and Development, 2012). The total input indicated that redundant medical resources in poverty areas were significantly higher than those in non-poverty areas. The Tobit regression model showed that the technical efficiency was proportional to the total annual incomes, the number of discharge patients, and the number of outpatient and emergency visits, while it was inversely proportional to total expenditure and the actual number of open beds. Technical efficiency was not associated with number of health care workers. CONCLUSION: The overall operational efficiency of the county-level MCHHs in Guangxi was low and needs to be improved. Regional economic differences affect the performances of hospitals. Health administrations should adjust and optimize the resource investments for the different areas. For the hospitals in poverty areas, policy makers should not only consider the hardware facilities investment, but also the introduction of advanced techniques and high-level medical personnel to improve their technical efficiency. PMID- 27552808 TI - Innovating in the medical device industry - challenges & opportunities ESB 2015 translational research symposium. AB - The European Society for Biomaterials 2015 Translational Research Symposium focused on 'Innovating in the Medical Device Industry - Challenges & Opportunities' from different perspectives, i.e., from a non-profit research organisation to a syndicate of small and medium-sized companies and large companies. Lecturers from regulatory consultants, industry and research institutions described the innovation process and regulatory processes (e.g., 510K, PMA, combination product) towards market approval. The aim of the present article is to summarise and explain the main statements made during the symposium, in terms of challenges and opportunities for medical device industries, in a constantly changing customer and regulatory environment. PMID- 27552807 TI - Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy. AB - Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM. PMID- 27552809 TI - Patient-reported outcomes of a multicenter phase 2 study investigating gemcitabine and stereotactic body radiation therapy in locally advanced pancreatic cancer. AB - PURPOSE: We previously reported clinical outcomes and physician-reported toxicity of gemcitabine and hypofractionated stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Here we prospectively investigate the impact of gemcitabine and SBRT on patient-reported quality of life (QoL). METHODS AND MATERIALS: Forty-nine LAPC patients received 33 Gy SBRT (6.6 Gy daily fractions) upfront or after <=3 doses of gemcitabine (1000 mg/m2) followed by gemcitabine until progression. European Organization for Research and Treatment of Cancer QoL core cancer (QLQ-C30) and pancreatic cancer-specific (European Organization for Research and Treatment of Cancer QLQ-PAN26) questionnaires were administered to patients pre-SBRT and at 4 to 6 weeks (first follow-up [1FUP]) and 4 months (2FUP) post-SBRT. Changes in QoL scores were deemed clinically relevant if median changes were at least 5 points in magnitude. RESULTS: Forty three (88%) patients completed pre-SBRT questionnaires. Of these, 88% and 51% completed questionnaires at 1FUP and 2FUP, respectively. There was no change in global QoL from pre-SBRT to 1FUP (P = .17) or 2FUP (P > .99). Statistical and clinical improvements in pancreatic pain (P = .001) and body image (P = .007) were observed from pre-SBRT to 1FUP. Patients with 1FUP and 2FUP questionnaires reported statistically and clinically improved body image (P = .016) by 4 months. Although pancreatic pain initially demonstrated statistical and clinical improvement (P = .020), scores returned to enrollment levels by 2FUP (P = .486). A statistical and clinical decline in role functioning (P = .002) was observed in patients at 2FUP. CONCLUSIONS: Global QoL scores are not reduced with gemcitabine and SBRT. In this exploratory analysis, patients experience clinically relevant short-term improvements in pancreatic cancer-specific symptoms. Previously demonstrated acceptable clinical outcomes combined with these favorable QoL data indicate that SBRT can be easily integrated with other systemic therapies and may be a potential standard of care option in patients with LAPC. PMID- 27552810 TI - Optimizing computed tomography simulation wait times in a busy radiation medicine program. AB - PURPOSE: An audit was conducted of patient schedules for computed tomography simulation (CT-Sim) scans within the Radiation Medicine Program at the Princess Margaret Cancer Centre to investigate opportunities for improved efficiencies, enhancing process, reducing rescanning rates, and decreasing wait times. METHODS AND MATERIALS: A 3-phased approach was undertaken to evaluate the current practice in the CT-Sim facility with a view toward implementing improvements. The first phase involved a review and assessment of the validity of current guidelines and protocols associated with 16 different disease sites. The second phase incorporated the use of a patient record and verification program MOSAIQ to capture the duration of each appointment. The last phase allocated additional time for patient-centered care and staff engagement. RESULTS: The audit revealed that efficiency could be achieved through staff training, updating protocols, and improving process coordination. With the exception of sarcoma, pediatric, and palliative patients who require unique management approaches, the duration for each CT-Sim appointment was successfully shortened for all disease sites by 22% to 33%, corresponding to a reduction of 10 to 15 minutes per appointment. Rescanning rates for patients requiring self-administered preparations before CT Sim procedures were also significantly reduced by enhancing processes to increase patient compliance. Implementation of procedural changes resulted in an overall net gain of 3060 minutes, equivalent to 102 additional 30-minute CT-Sim appointment slots available for each month. CONCLUSIONS: This retrospective evaluation, review, and optimization of CT-Sim guidelines and practices identified opportunities to shorten appointment timeslots, and reduce rescanning rates for CT-Sim procedures, thereby significantly shortening wait times and improving access to service for our patients. PMID- 27552811 TI - Assessment of dose variation for accelerated partial-breast irradiation using rigid and deformable image registrations. AB - PURPOSE: The aim of this study was to estimate the delivered dose to the target and organs at risk (OAR) for external beam accelerated partial-breast irradiation (APBI) accounting for day-to-day setup uncertainties, using rigid and deformable image registration. METHODS AND MATERIALS: One planning computed tomography (CT) scan and 5 cone beam CT scans for each of 25 patients previously treated with tangential breast radiation therapy were used. All cone beam CT scans were registered to the planning CT scan using 3 techniques: (1) rigid registration based on bony anatomy only, (2) rigid registration based on soft-tissue only, and (3) deformable image registration. For each patient, 4 dose distributions were calculated for APBI. The first dose distribution was the original plan. The other 3 were "dose-of-the-day" for each of the registration approaches. The effects of image registrations on estimating delivered dose to targets and OAR were determined. RESULTS: The average reductions in V95 (percentage of the PTV that received 95% of the prescribed dose) were 6%, 7%, and 5% for bone, soft-tissue, and deformable registrations, respectively. The average increase in mean dose to the heart were 9%, 9%, and 18% for bone, soft-tissue, and deformable registrations, respectively, whereas the average increase in maximum dose to the contralateral breast were 19%, 20%, and 28%, respectively. CONCLUSIONS: The results of this study have shown that there are differences between the planned and estimated delivered dose for APBI because of day-to-day setup uncertainties that may need to be accounted for. Estimated dosimetric impact of setup variation and breast deformation assessed using deformable registration was greater for OARs and smaller for target volumes compared to rigid registration. PMID- 27552812 TI - Peritumoral Brain Edema in Meningiomas Depends on Aquaporin-4 Expression and Not on Tumor Grade, Tumor Volume, Cell Count, or Ki-67 Labeling Index. AB - PURPOSE: The aim of this study was to investigate to which degree the peritumoral brain edema in patients with meningiomas depends on aquaporin-4 (AQP4) expression, tumor grade, tumor volume, Ki-67 expression, and cell count. PROCEDURES: Thirty-three patients (25 women, 8 men; mean age 56.6 +/- 16.0 years) with an intracranial meningioma underwent a standardized magnetic resonance (MR) examination prior to surgical resection. Edema indices (EIs) and tumor volumes were measured on the MR images. Tumor grade was classified according to the World Health Organization, and the proliferation index was estimated on Ki-67 antigen stained specimens. Tumor cell count was evaluated. Eighteen specimens were stained for AQP4 expressioon. RESULTS: Significant intergroup differences between AQP4 expression grades and EIs were observed (P = 0.03), and a positive correlation was detected between EIs and AQP4 expression grades (r = 0.54; P < 0.05). A ROC analysis with EI as a test variable revealed an AUC of 0.77 (95 % CI 0.55-0.99) for the prediction of a moderate-to-strong AQP4 expression. An EI >=1.5 predicted a moderate-to-high AQP4 expression with a sensitivity of 77 % and a specificity of 60 %. EI values of 2.2 and 3.5 reached sensitivity/specificity values of 69/80 % and 54/100 %, respectively. The AQP4 expression did not show any significant correlations with tumor grading, tumor volume, Ki-67 expression, or cell count. Moreover, we observed no significant positive or negative correlations between the EI and tumor grading (P = 0.7), tumor volume (P = 0.19), Ki-67 index (P = 0.9), and cell count (P = 0.34). CONCLUSION: Peritumoral brain edema in patients with meningiomas may depend on AQP4 expression grades and not on tumor grade, tumor volume, Ki-67 expression, and cell count. The amount of edema predicted AQP4 expressions with moderate-to-good sensitivity and specificity. PMID- 27552814 TI - Editorial: Farewell and Thanks. PMID- 27552815 TI - Weighing the cost of educational inflation in undergraduate medical education. AB - Despite the fact that the length of medical school training has remained stable for many years, the expectations of graduating medical students (and the schools that train them) continue to increase. In this Reflection, the authors discuss motives for educational inflation and suggest that these are likely innocent, well-intentioned, and subconscious-and include both a propensity to increase expectations of ourselves and others over time, and a reluctance to reduce training content and expectations. They then discuss potential risks of educational inflation, including reduced emphasis on core knowledge and clinical skills, and adverse effects on the emotional, psychological, and financial wellbeing of students. While acknowledging the need to change curricula to improve learning and clinical outcomes, the authors proffer that it is naive to assume that we can inflate educational expectations at no additional cost. They suggest that before implementing and/or mandating change, we should consider of all the costs that medical schools and students might incur, including opportunity costs and the impact on the emotional and financial wellbeing of students. They propose a cost-effectiveness framework for medical education and advocate prioritization of interventions that improve learning outcomes with no additional costs or are cost-saving without adversely impacting learning outcomes. When there is an additional cost for improved learning outcomes or a decline in learning outcomes as a result of cost saving interventions, they suggest careful consideration and justification of this trade-off. And when there are neither improved learning outcomes nor cost savings they recommend resisting the urge to change. PMID- 27552813 TI - Online information seeking by patients with bipolar disorder: results from an international multisite survey. AB - BACKGROUND: Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. METHODS: A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. RESULTS: 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. CONCLUSION: Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites. PMID- 27552818 TI - Linking Genetic Kinship and Demographic Analyses to Characterize Dispersal: Methods and Application to Blanding's Turtle. AB - Characterizing how frequently, and at what life stages and spatial scales, dispersal occurs can be difficult, especially for species with cryptic juvenile periods and long reproductive life spans. Using a combination of mark-recapture information, microsatellite genetic data, and demographic simulations, we characterize natal and breeding dispersal patterns in the long-lived, slow maturing, and endangered Blanding's turtle (Emydoidea blandingii), focusing on nesting females. We captured and genotyped 310 individual Blanding's turtles (including 220 nesting females) in a central Wisconsin population from 2010 to 2013, with additional information on movements among 3 focal nesting areas within this population available from carapace-marking conducted from 2001 to 2009. Mark recapture analyses indicated that dispersal among the 3 focal nesting areas was infrequent (<0.03 annual probability). Dyads of females with inferred first-order relationships were more likely to be found within the same nesting area than split between areas, and the proportion of related dyads declined with increasing distance among nesting areas. The observed distribution of related dyads for nesting females was consistent with a probability of natal dispersal at first breeding between nearby nesting areas of approximately 0.1 based on demographic simulations. Our simulation-based estimates of infrequent female dispersal were corroborated by significant spatial genetic autocorrelation among nesting females at scales of <500 m. Nevertheless, a lack of spatial genetic autocorrelation among non-nesting turtles (males and females) suggested extensive local connectivity, possibly mediated by male movements or long-distance movements made by females between terrestrial nesting areas and aquatic habitats. We show here that coupling genetic and demographic information with simulations of individual based population models can be an effective approach for untangling the contributions of natal and breeding dispersal to spatial ecology. PMID- 27552816 TI - The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population. AB - Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerability-stress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis. The purpose of the present study was to investigate impact of FKBP5 on schizophrenia in Serbian patients and to explore relationship between genetic variants and neuroticism by using the case-sibling-control design. In 158 subjects, we measured psychotic experiences, childhood trauma and neuroticism. Nine single-nucleotide polymorphisms (rs9295158, rs3800373, rs9740080, rs737054, rs6926133, rs9380529, rs9394314, rs2766533 and rs12200498) were genotyped. The genetic influence was modeled using logistic regression, and the relationship between genetic variants and neuroticism was assessed by linear mixed model. Our results revealed genetic main effect of FKBP5 risk alleles (A allele of rs9296158 and T allele of rs3800373) and AGTC "risk" haplotype combination (rs9296158, rs3800373, rs9470080 and rs737054, respectively) on schizophrenia, particularly when childhood trauma was set as a confounding factor. We confirmed strong relationship between neuroticism and psychotic experiences in patients and siblings and further showed relationship between higher levels of neuroticism and FKBP5 risk variants suggesting potential link between biological and psychosocial risk factors. Our data support previous findings that trauma exposure shapes FKBP5 impact on schizophrenia. PMID- 27552817 TI - Evaluation of Rumex hastatus D. Don for cytotoxic potential against HeLa and NIH/3T3 cell lines: chemical characterization of chloroform fraction and identification of bioactive compounds. AB - BACKGROUND: The importance of Rumex genus and the renowned ethnopharmacological and biological potentials of Rumex hastatus is evident from the previous reports. Recently the R. hastatus has been evaluated for anticancer potential against HepG2, MCF7 or LNCaP cell lines with considerable cytotoxicity. We also reported the anti-tumor and anti-angiogenic potentials of R. hastatus. The current study has been arranged to evaluate cytotoxic potential of this plant against HeLa and NIH/3T3 cell lines and sort out the most active fraction of R. hastatus along with the identification of bioactive compounds responsible for cytotoxicity. METHODS: The cytotoxic potential of methanolic extract and sub-fractions of R. hastatus was performed following (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyl tetrazolium bromide) MTT calorimetric assay. Four concentrations (500, 250, 125 and 62.5 MUg/ml) of each sample were used against both cell lines. Two cell lines i.e. HeLa and NIH/3T3 were used in the assay. Furthermore, chemical characterization of chloroform fraction was performed by GC-MS analysis. RESULTS: The current investigational study demonstrates that all the solvent fractions of R. hastatus were active against HeLa and NIH/3T3 cell lines. Among all the fractions, chloroform fraction was dominant in activity against both cell lines. The observed IC50 values of chloroform fraction were 151.52 and 53.37 MUg/ml against HeLa and NIH/3T3 respectively. The GC-MS analysis of chloroform fraction revealed the identification of 78 compounds with the identification of bioactive ones like ar-tumerone, phytol, dihydrojasmone, sitostenone etc. CONCLUSION: It can be concluded from our results that Rumex hastatus D. Don possess strong cytotoxic potential. Moreover, the observed IC50 values and GC-MS analysis of chloroform fraction reveal that most of the bioactive compounds are in chloroform fraction. It can be further deduce that the chloroform fraction is a suitable target for the isolation of compounds having potential role in cancer therapy. PMID- 27552820 TI - Circulating Erythrocyte Microparticles and the Biochemical Extent of Myocardial Injury in ST Elevation Myocardial Infarction. AB - OBJECTIVES: Red blood cell microparticles (RBCm) have potential adverse vascular effects and they have been shown to be elevated in ST elevation myocardial infarction (STEMI). The purpose of this study is to investigate their relationship with biochemical infarct size. METHODS: RBCm were quantified with flow cytometry in blood drawn from 60 STEMI patients after a primary angioplasty. The creatine kinase-myocardial brain fraction (CK-MB) was measured at predefined time points and the area under the curve (AUC) was calculated. RESULTS: RBCm count was correlated with CK-MB AUC (Spearman's rho = 0.83, p < 0.001). The CK-MB AUC values per RBCm quartile (lower to upper) were: 3,351 (2,452-3,608), 5,005 (4,450-5,424), 5,903 (4,862-10,594), and 8,406 (6,848-12,782) ng * h/ml, respectively. From lower to upper quartiles, the maximal troponin I values were: 42.2 (23.3-49.3), 49.6 (28.8-54.1), 59.2 (41.4-77.3), and 69.1 (48.0-77.5) ng/ml (p = 0.005). In multivariable analysis, RBCm remained a significant predictor of CK-MB AUC (standardized beta = 0.63, adjusted p = 0.001). CONCLUSIONS: Erythrocyte microparticles appear to be related to the total myocardial damage biomarker output. The exact pathophysiologic routes, if any, for this interaction remain to be identified. However, these results suggest that erythrocytes may be a - thus far virtually ignored - player in the pathogenesis of ischemic injury. PMID- 27552822 TI - The Lucent Liver Sign. PMID- 27552823 TI - An Investigation of Stimulant Effects on the EEG of Children With Attention Deficit/Hyperactivity Disorder. AB - Stimulant medications are the most commonly prescribed treatment for Attention Deficit/Hyperactivity Disorder (AD/HD). These medications result in a normalization of the EEG. However, past research has found that complete normalization of the EEG is not always achieved. One reason for this may be that studies have used different medications interchangeably, or groups of subjects on different stimulants. This study investigated whether methylphenidate and dexamphetamine produce different levels of normalization of the EEG in children with AD/HD. Three groups of 20 boys participated in this study. There were 2 groups with a diagnosis of AD/HD; one group, good responders to methylphenidate, and the second, good responders to dexamphetamine. The third group was a normal control group. Baseline EEGs were recorded using an eyes-closed resting condition, and analyzed for total power and relative delta, theta, alpha, and beta. Subjects were placed on a 6-month trial of methylphenidate or dexamphetamine, after which a second EEG was recorded. At baseline, the children with AD/HD had elevated relative theta, less relative alpha and beta compared with controls. Baseline differences were found between the two medication groups, with the dexamphetamine group having greater EEG abnormalities than the methylphenidate group. The results indicate that good responders to methylphenidate and dexamphetamine have different EEG profiles when assessed before medication, and these differences may represent different underlying central nervous system deficits. The 2 medications were found to result in substantial normalization of the EEG, with no significant differences in EEG changes occurring between the 2 medications. This indicates that the degree of pretreatment EEG abnormality was the major factor contributing to the degree of normalization of the EEG. As good responders to the 2 medications appear to have different central nervous system abnormalities, it is recommended that stimulant medications be treated independently and not used interchangeably in research and treatment of AD/HD. PMID- 27552821 TI - Effects of an employee exercise programme on mental health. AB - Background: Prior research indicates that workplace wellness programmes (WWPs) are generally associated with lowered healthcare costs and improved employee health. Despite the importance of mental well-being in workplace productivity and attendance, few WWP studies have focused on improvements in psychological well being. Aims: To examine the effects of the Bruin Health Improvement Program (BHIP), a 3-month exercise and nutrition WWP, on seven domains of health: physical and mental health, stress, energy level, social satisfaction, self efficacy and quality of life. Methods: Using data from BHIP completers, we conducted multiple one-way multivariate analyses of variance and follow-up univariate t-tests to examine changes in physical and mental health, stress, energy level, social satisfaction, self-efficacy and quality of life. Effect sizes were also calculated post hoc to determine the magnitude of each effect. Results: Results for the 281 participants reveal significant improvements across all seven domains (P < 0.001). Effect sizes ranged from 0.19 to 0.67. Conclusions: This study is unique in revealing the effects of a WWP on multiple domains of psychological well-being. Given rising healthcare costs associated with mental health, targeting mental health through WWP may be an effective strategy for reducing indirect healthcare costs associated with absenteeism and presenteeism. PMID- 27552824 TI - Mathematical Modeling and Simulation of an Occlusion Device in a Blood Vessel. AB - An occlusion device is placed in an abnormal opening of the heart or its surrounding vessels to regain normal blood flow. There are various occlusion devices available for treatment of various congenital heart defects like PDA, ASD, etc. However, they have limitations like residual shunting, erosion of tissue, displacement and breakage of device, thrombus formation and sudden death. To improve efficiency and to reduce failure of occlusion devices, it is important to simulate blood flow through defect before and after placement of device. It is also important to evaluate stresses and forces exerted by blood flow on device and by the device on the vessel wall. Contact friction between device and vessel wall plays a crucial role in anchoring the device. The objective is to develop a framework to determine conditions to restrict dislocation of device in terms of contact friction. Typical occlusion devices are porous initially and later due to thrombogenesis, their porosity reduces until eventually it acts as a natural permanent plug. Thus, a porous sponge is a good model for an occlusion device. The mathematical model developed here is for differential pressure causing incipient movement of device, and minimum value of contact friction for restricting movement of the device for two shapes, cylindrical and conical, in uncompressed as well as pre compressed forms. The model for differential pressure is fitted by conducting physical experiment with sponge. Mathematically, porosity is modeled using viscous resistance and inertial resistance which are calculated by experiment and simulation with ANSYS. We perform computer experiments (simulations) on a cylindrical device in a cylindrical vessel and on a conical device in a tapered vessel to determine the differential pressure across the device and hence contact friction with varied porosity under boundary conditions as in body. The contact friction required to retain device is lesser in case of conical device compared to cylindrical device. As compression of device increases, friction require to retain it decreases. Hence, lesser porosity results in larger differential pressure and lesser compression which will eventually need higher friction values to retain the device. PMID- 27552825 TI - Serum Potassium Profile and Associated Factors in Incident Peritoneal Dialysis Patients. AB - BACKGROUND/AIMS: Abnormal potassium profiles are common in peritoneal dialysis (PD) patients. We studied the factors associated with serum potassium profiles in incident PD patients. METHODS: Patients were enrolled from two hospital facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. RESULTS: There were 168 men and 151 women (mean age, 50.8 years). Blood urea nitrogen (BUN), creatinine (Cr), and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01 1.03, p = 0.001) and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029) levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. CONCLUSION: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients. PMID- 27552826 TI - [Surgery of benign vocal fold lesions]. AB - Surgical treatment of benign vocal fold lesions can be indicated for clinical or functional reasons. The principles of phonosurgery have to be maintained in either case. The appropriate phonosurgical technique depends on the type of vocal fold lesion. Depending on the findings, phonosurgery aims to maintain or improve voice quality. The evaluation of clinical and functional results includes indirect laryngoscopy, videostroboscopy, and voice analysis. PMID- 27552827 TI - Multimodal MRI for early diabetic mild cognitive impairment: study protocol of a prospective diagnostic trial. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a risk factor for dementia. Mild cognitive impairment (MCI), an intermediary state between normal cognition and dementia, often occurs during the prodromal diabetic stage, making early diagnosis and intervention of MCI very important. Latest neuroimaging techniques revealed some underlying microstructure alterations for diabetic MCI, from certain aspects. But there still lacks an integrated multimodal MRI system to detect early neuroimaging changes in diabetic MCI patients. Thus, we intended to conduct a diagnostic trial using multimodal MRI techniques to detect early diabetic MCI that is determined by the Montreal Cognitive Assessment (MoCA). METHODS: In this study, healthy controls, prodromal diabetes and diabetes subjects (53 subjects/group) aged 40-60 years will be recruited from the physical examination center of Tangdu Hospital. The neuroimaging and psychometric measurements will be repeated at a 0.5 year-interval for 2.5 years' follow-up. The primary outcome measures are 1) Microstructural and functional alterations revealed with multimodal MRI scans including structure magnetic resonance imaging (sMRI), resting state functional magnetic resonance imaging (rs-fMRI), diffusion kurtosis imaging (DKI), and three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL); 2) Cognition evaluation with MoCA. The second outcome measures are obesity, metabolic characteristics, lifestyle and quality of life. DISCUSSION: The study will provide evidence for the potential use of multimodal MRI techniques with psychometric evaluation in diagnosing MCI at prodromal diabetic stage so as to help decision making in early intervention and improve the prognosis of T2DM. TRIAL REGISTRATION: This study has been registered to ClinicalTrials.gov ( NCT02420470 ) on April 2, 2015 and published on July 29, 2015. PMID- 27552828 TI - Successful continual intratympanic steroid injection therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis. AB - OBJECTIVE: To report the treatment efficacy of continual intratympanic steroid injection (ITSI) therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis. PATIENT: A 49-year-old female diagnosed with relapsing polychondritis at the age of 45 years and who had been treated with corticosteroids and immunosuppressants developed sensorineural hearing loss in the left ear. INTERVENTION: Her unilateral hearing loss did not recover despite receiving one cyclophosphamide pulse treatment, one methylprednisolone pulse treatment, and weekly leukapheresis. Thus, we decided to initiate weekly ITSI therapy. MAIN OUTCOME MEASURE: Pure tone audiometry. RESULTS: A week after the first ITSI treatment, the patient's hearing improved. We continued ITSI therapy and attempted to extend the interval between treatments, but her hearing worsened when ITSI therapy was delivered at 2- to 3-week intervals. Thus, we returned ITSI therapy to once per week for 21 months (total of 71 treatments). She experienced no adverse events, like tympanic perforation, and 1 year after terminating the therapy, her hearing remained stable and did not worsen. CONCLUSIONS: Continual, weekly ITSI therapy was effective in treating sensorineural hearing loss accompanied by relapsing polychondritis. ITSI therapy may be a promising treatment option for sensorineural hearing loss caused by autoimmune disease. PMID- 27552829 TI - Novel syndrome with conductive hearing loss and congenital glaucoma in three generations. AB - The objective of this paper was to describe the clinical and otological findings in multiple members of a family with congenital glaucoma, cardiac anomaly, and conductive hearing loss due to ossicular chain anomalies. We performed a retrospective review of the medical charts and otological materials of multiple members of the same family. Congenital glaucoma and hearing loss were inherited by the proband and her daughter, son, and mother, suggesting autosomal dominant inheritance. The son and daughter also showed atrial septal defects. Exploratory tympanotomies revealed anomalies of the long process of the incus in the proband and her daughter, and tympanoplasty improved hearing loss in both patients. This represents the first description of coexisting congenital glaucoma and conductive hearing loss due to ossicular chain anomalies in multiple members of a single family. PMID- 27552830 TI - Adult T-cell leukemia/lymphoma in patients with head and neck cancer after S-1 chemotherapy. AB - OBJECTIVE: One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV 1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients. METHODS: The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013. RESULTS: Of 146 patients, 17 were HTLV-1 positive and 6 developed ATLL. There was a significant relationship between ATLL development and administration of S-1 chemotherapy (p=0.0003), but not with use of radiotherapy, surgery or other drugs. CONCLUSION: The involvement of S-1 chemotherapy in ATLL development suggests that a test for HTLV-1 antibody should be performed before treatment and that S-1 should not be administered in HTLV-1 positive patients with head and neck carcinoma. PMID- 27552831 TI - A stable isotope method for in vivo assessment of human insulin synthesis and secretion. AB - AIMS: In vitro, beta cells immediately secrete stored but readily releasable insulin in response to a rise of glucose. During a prolonged insulin response, this is followed by newly synthesized insulin. Our aim was to develop an in vivo test to determine the ratio between readily available and newly synthesized insulin after a stimulus in humans by labelling newly synthesized insulin. METHODS: A stable isotope tracer of 1.0 g 13C leucine with C-peptide as target peptide was administered 45 min prior to 75 g glucose load of a frequently blood sampled 210-min oral glucose tolerance test (OGTT). Our OGTT also encompassed collection of urine, which has a high content of C-peptide. Prior, the optimal conditions under which the tracer 13C leucine was administered for enrichment of (pre) proinsulin were established. Also, techniques to obtain urinary C-peptide under highly purified circumstances were set up. Our main outcome measure was the stable isotope enrichment of de novo C-peptide, which we related to early plasma insulin and glucose AUC. Twelve healthy Caucasian individuals (M4F8, age 41.8 +/- 2.3, BMI 28.3 +/- 1.7) with normal glucose tolerance underwent our OGTT. RESULTS: We found that during a 75-g OGTT, newly synthesized insulin contributed approximately 20 % of total insulin secretion. The pattern of isotope enrichment obtained by collecting multiple urine voids was suggestive that the newly synthesized insulin contributes to the late phase of insulin secretion. De novo C peptide correlated negatively with both early plasma insulin AUC (r = -0.629, P = 0.028) and early plasma glucose AUC (r = -0.605, P = 0.037). CONCLUSIONS: With stable isotope technique added to OGTT, we were able to measure newly synthesized insulin in healthy individuals. This new technique holds the promise that it is feasible to develop a direct in vivo beta cell function test. PMID- 27552832 TI - Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma. AB - AIMS: To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis. METHODS: Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression. RESULTS: Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 +/- 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 +/- 9 vs. 66.8 +/- 10 years, p = 0.68), but were more likely to have a cancer stage >=3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 +/- 0.14 and 1.79 +/- 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival. CONCLUSIONS: Insulin resistance is associated with the aggressiveness of PDAC. PMID- 27552833 TI - Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy. AB - AIMS: Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The alpha2 adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats. However, SST and BRM effects on microvascular cells have not yet been studied. We investigated the behaviour of these drugs on the crosstalk between microvasculature and neuroretina. METHODS: Expression of SST receptors 1 5 in human retinal pericytes (HRP) was checked. We subsequently evaluated the effects of diabetic-like conditions (high glucose and/or hypoxia) with/without SST/BRM on HRP survival. Endothelial cells (EC) and photoreceptors were maintained in the above conditions and their conditioned media (CM) used to culture HRP. Vice versa, HRP-CM was used on EC and photoreceptors. Survival parameters were assessed. RESULTS: HRP express the SST receptor 1 (SSTR1). Glucose fluctuations mimicking those occurring in diabetic subjects are more damaging for pericytes and photoreceptors than stable high glucose and hypoxic conditions. SST/BRM added to HRP in diabetic-like conditions decrease EC apoptosis. However, neither SST nor BRM changed the response of pericytes and neuroretina-vascular crosstalk under diabetic-like conditions. CONCLUSIONS: Retinal pericytes express SSTR1, indicating that they can be a target for SST. Exposure to SST/BRM had no adverse effects, direct or mediated by the neuroretina, suggesting that these molecules could be safely evaluated for the treatment of ocular diseases. PMID- 27552835 TI - Regulatory agencies should engage in drug pricing. PMID- 27552834 TI - Prolonged episodes of hypoglycaemia in HNF4A-MODY mutation carriers with IGT. Evidence of persistent hyperinsulinism into early adulthood. AB - AIMS: HNF4A is an established cause of maturity onset diabetes of the young (MODY). Congenital hyperinsulinism can also be associated with mutations in the HNF4A gene. A dual phenotype is observed in HNF4A-MODY with hyperinsulinaemic hypoglycaemia in the neonatal period progressing to diabetes in adulthood. The nature and timing of the transition remain poorly defined. We performed an observational study to establish changes in glycaemia and insulin secretion over a 6-year period. We investigated glycaemic variability and hypoglycaemia in HNF4A MODY using a continuous glucose monitoring system (CGMS). METHODS: An OGTT with measurement of glucose, insulin and C-peptide was performed in HNF4A participants with diabetes mellitus (DM) (n = 14), HNF4A-IGT (n = 7) and age- and BMI-matched MODY negative family members (n = 10). Serial assessment was performed in the HNF4A-IGT cohort. In a subset of HNF4A-MODY mutation carriers (n = 10), CGMS was applied over a 72-h period. RESULTS: There was no deterioration in glycaemic control in the HNF4A-IGT cohort. The fasting glucose-to-insulin ratio was significantly lower in the HNF4A-IGT cohort when compared to the normal control group (0.13 vs. 0.24, p = 0.03). CGMS profiling demonstrated prolonged periods of hypoglycaemia in the HNF4A-IGT group when compared to the HNF4A-DM group (432 vs. 138 min p = 0.04). CONCLUSIONS: In a young adult HNF4A-IGT cohort, we demonstrate preserved glucose, insulin and C-peptide secretory responses to oral glucose. Utilising CGMS, prolonged periods of hypoglycaemia are evident despite a median age of 21 years. We propose a prolonged hyperinsulinaemic phase into adulthood is responsible for the notable hypoglycaemic episodes. PMID- 27552836 TI - Prefrontal Cortical GABAergic Dysfunction Contributes to Aberrant UP-State Duration in APP Knockout Mice. AB - Genetic and biochemical studies have focused on the role of amyloid beta protein in the pathogenesis of Alzheimer's disease. In comparison, the physiological roles of its precursor protein, amyloid precursor protein (APP), in synaptic and network activity is less well studied. Using an APP knockout (APP-/-) mouse model, we show that the duration of UP state, which is a key feature of cortical synaptic integration occurring predominantly during slow-wave sleep, is significantly increased in the prefrontal cortex (PFC) in the absence of APP. This was accompanied by a specific reduction in the glutamine synthetase and tissue GABA content and sequential upregulation in the levels of GABABR expression. Pharmacological reinforcement of GABA signaling by application of either a GABA uptake inhibitor or an agonist of GABABR rescued the abnormality of UP-state duration and the former rescues altered GABABR expression as well. In addition to revealing an essential role of APP in the regulation of PFC network function, this study evidences the viability of GABA signaling pathway and its receptors, especially GABABRs, as a target for the treatment of aberrant neural network activity and thus information processing. PMID- 27552837 TI - Effect of Instrument Design and Access Outlines on the Removal of Root Canal Obturation Materials in Oval-shaped Canals. AB - INTRODUCTION: The aim of this study was to compare the effectiveness of TRUShape (TS) instruments with ProFile Vortex Blue (VB) instruments for the removal of obturation materials during retreatment of single-canal mandibular premolars performed through 2 access outlines. METHODS: Initial root canal treatment was completed through a contracted endodontic cavity (CEC) design. Canals were instrumented to an F2 ProTaper instrument, obturated with warm lateral condensation of gutta-percha with AH Plus sealer, and allowed to set for 30 days at 37 degrees C and 100% humidity. For retreatment, specimens were divided into 2 groups (n = 24) on the basis of access outline, CEC or traditional endodontic cavity (TEC). Retreatment was initiated by using ProTaper Retreatment instruments (D1-D3). Specimens were then stratified, further divided (n = 12), and reinstrumented up to TS 40 .06v or 40 .06 VB. Irrigation was performed by using 8.25% NaOCl and QMix 2in1. Retreatment time was recorded. Teeth were sectioned and photographed, and the percentage of remaining obturation materials was measured. Data were analyzed with Kruskal-Wallis analysis of variance for two factor tests (alpha < 0.05). RESULTS: The interaction between access design and instrument type showed that the combination of CEC-VB presented significantly higher amounts of remaining obturation materials on the canal surface when compared with TEC-VB, CEC-TS, and TEC-TS (P <= .05). None of these other combinations were different from each other (P > .05). Significantly more time was required for retreatment with CEC-TS (27.68 +/- 1.4 minutes) than the other groups (P < .05). CONCLUSIONS: Neither retreatment protocol was able to completely eliminate all obturation materials from the root canal surface of mandibular premolars. However, in the presence of a CEC access design, using TS instruments removed more obturating material in single-rooted, oval-shaped canals. PMID- 27552838 TI - Uncontrolled Removal of Dentin during In Vitro Ultrasonic Irrigant Activation in Curved Root Canals. AB - INTRODUCTION: The aim of this study was to examine the effect of file type and activation time on the uncontrolled removal of dentin during in vitro ultrasonic irrigant activation in prepared curved root canals. METHODS: Seventy-two curved mesial root canals of human mandibular molars were prepared to size 35/.04 taper. The specimens were randomly allocated to 4 groups (n = 18). Two milliliters of 2% sodium hypochlorite were delivered 3 times to each root canal, and the irrigant was ultrasonically activated every time for 10 seconds at 35% power either by a ultrasonic K-file (group A), an Irrisafe file (Acteon Satelec, Merignac, France) (group B), or a smooth wire (group C). The same specimens also received further activation continuously for another 30 seconds. No activation took place in group D. Specimens were scanned by micro-computed tomographic imaging before and after preparation and after the first and second activation period. Scans were coregistered and segmented, and the amount of dentin removed during activation was quantified by morphological operations. Results were analyzed by nonparametric statistical tests (alpha = 0.05). RESULTS: Defects with a maximum depth of 0.18 mm were identified. Both the type of file and activation time affected the removal of dentin (P <= .002 and P <= .031, respectively). K-files removed more dentin than Irrisafe files and smooth wires in the coronal and middle third. All files removed comparable amounts in the apical third. CONCLUSIONS: All 3 types of files may result in uncontrolled removal of dentin. A longer activation time may increase this effect. PMID- 27552839 TI - Factors Associated with Apical Periodontitis: A Multilevel Analysis. AB - INTRODUCTION: Ignoring the cluster effect is a common statistical oversight that is also observed in endodontic research. The aim of this study was to explore the use of multilevel modeling in investigating the effect of tooth-level and patient level factors on apical periodontitis (AP). METHODS: A random sample of digital panoramic radiographs from the database of a dental hospital was evaluated. Two calibrated examiners (kappa >= 0.89) assessed the technical quality of the root fillings and the radiographic periapical health status by using the periapical index. Descriptive statistical analysis was carried out, followed by multilevel modeling by using tooth-level and patient-level predictors. Model fit information was obtained, and the findings of the best-fit model were reported. RESULTS: A total of 6409 teeth were included in the analysis. The predicted probability of a tooth having AP was 0.42%. There was a statistically significant variability between patients (P < .05). Approximately 53.16% of the variability was accounted for by the patients, leaving 46.84% of the variability to teeth or other factors. Posterior tooth, inadequate root filling, and age were found to be significantly associated with AP (P < .05). CONCLUSIONS: Multilevel modeling is a valid and efficient statistical method in analyzing AP data. The predicted probability of a tooth having AP was generally small, but there was great variation between individuals. Posterior teeth and those with poor quality root filling were found to be more frequently associated with AP. On the patient level, advancing age was a factor significantly associated with AP. PMID- 27552841 TI - The Challenge of Community Representation. AB - Although community advisory boards (CABs) are widely used in clinical research, there is limited data regarding their composition and structure, especially in Africa. Our research provides the first qualitative study of the membership practices, selection methods, and qualifications of the six major HIV research centers that comprise the Ugandan National CAB Network (UNCN). Researchers conducted interviews ( n = 45) with CAB members and research liaisons at each of the sites. While selection practices and demographics varied between the sites, all six CABs exclusively followed a broad community membership model. Results suggest successful CABs are context dependent and thus distinct guidelines may be needed based on variables including CAB funding level, representation model, and research focus. PMID- 27552840 TI - Efficacy of a workplace osteoporosis prevention intervention: a cluster randomized trial. AB - BACKGROUND: Osteoporosis is a debilitating disease. Adequate calcium consumption and physical activity are the two major modifiable risk factors. This paper describes the major outcomes and efficacy of a workplace-based targeted behaviour change intervention to improve the dietary and physical activity behaviours of working women in sedentary occupations in Singapore. METHODS: A cluster randomized design was used, comparing the efficacy of a tailored intervention to standard care. Workplaces were the units of randomization and intervention. Sixteen workplaces were recruited from a pool of 97, and randomly assigned to intervention and control arms (eight workplaces in each). Women meeting specified inclusion criteria were then recruited to participate. Workplaces in the intervention arm received three participatory workshops and organization-wide educational activities. Workplaces in the control/standard care arm received print resources. Outcome measures were calcium intake (milligrams/day) and physical activity level (duration: minutes/week), measured at baseline, 4 weeks and 6 months post intervention. Adjusted cluster-level analyses were conducted comparing changes in intervention versus control groups, following intention-to treat principles and CONSORT guidelines. RESULTS: Workplaces in the intervention group reported a significantly greater increase in calcium intake and duration of load-bearing moderate to vigorous physical activity (MVPA) compared with the standard care control group. Four weeks after intervention, the difference in adjusted mean calcium intake was 343.2 mg/day (95 % CI = 337.4 to 349.0, p < .0005) and the difference in adjusted mean load-bearing MVPA was 55.6 min/week (95 % CI = 54.5 to 56.6, p < .0005). Six months post intervention, the mean differences attenuated slightly to 290.5 mg/day (95 % CI = 285.3 to 295.7, p < .0005) and 50.9 min/week (95 % CI =49.3 to 52.6, p < .0005) respectively. CONCLUSION: This workplace-based intervention substantially improved calcium intake and load-bearing moderate to vigorous physical activity 6 months after the intervention began. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12616000079448 . Registered 25 January 2016 (retrospectively registered). PMID- 27552842 TI - Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis. AB - BACKGROUND: Women with high levels of mammographic density (MD) have a four- to six-fold increased risk of developing breast cancer; however, most neither have a prevalent tumor nor will they develop one. Magnetic resonance imaging (MRI) studies suggest that background parenchymal enhancement, an indicator of vascularity, is related to increased breast cancer risk. Correlations of microvessel density (MVD) in tissue, MD and biopsy diagnosis have not been defined, and we investigated these relationships among 218 women referred for biopsy. METHODS: MVD was determined by counting CD31-positive vessels in whole sections of breast biopsies in three representative areas; average MVD was transformed to approximate normality. Using digital mammograms, we quantified MD volume with single X-ray absorptiometry. We used linear regression to evaluate associations between MVD and MD adjusted for age and body mass index (BMI) overall, and stratified by biopsy diagnosis: cases (in situ or invasive cancer, n = 44) versus non-cases (non-proliferative or proliferative benign breast disease, n = 174). Logistic regression adjusted for age, BMI, and MD was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between MVD and biopsy diagnosis. We also assessed whether the MVD-breast cancer association varied by MD. RESULTS: MVD and MD were not consistently associated. Higher MVD was significantly associated with higher odds of in situ/invasive disease (ORAdjusted = 1.69, 95 % CI = 1.17-2.44). MVD-breast cancer associations were strongest among women with greater non-dense volume. CONCLUSIONS: Increased MVD in tissues is associated with breast cancer, independently of MD, consistent with MRI findings suggestive of its possible value as a radiological cancer biomarker. PMID- 27552843 TI - CAZyChip: dynamic assessment of exploration of glycoside hydrolases in microbial ecosystems. AB - BACKGROUND: Microorganisms constitute a reservoir of enzymes involved in environmental carbon cycling and degradation of plant polysaccharides through their production of a vast variety of Glycoside Hydrolases (GH). The CAZyChip was developed to allow a rapid characterization at transcriptomic level of these GHs and to identify enzymes acting on hydrolysis of polysaccharides or glycans. RESULTS: This DNA biochip contains the signature of 55,220 bacterial GHs available in the CAZy database. Probes were designed using two softwares, and microarrays were directly synthesized using the in situ ink-jet technology. CAZyChip specificity and reproducibility was validated by hybridization of known GHs RNA extracted from recombinant E. coli strains, which were previously identified by a functional metagenomic approach. The GHs arsenal was also studied in bioprocess conditions using rumen derived microbiota. CONCLUSIONS: The CAZyChip appears to be a user friendly tool for profiling the expression of a large variety of GHs. It can be used to study temporal variations of functional diversity, thereby facilitating the identification of new efficient candidates for enzymatic conversions from various ecosystems. PMID- 27552844 TI - Combined hepatocellular and cholangiocarcinoma originating from the same clone: a pathomolecular evidence-based study. AB - BACKGROUND: Combined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); however, its cellular origin remains unclear. The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC. METHODS: The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC (SHC). Loss of heterozygosity (LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC. Expression of hepatocyte markers [hepatocyte paraffin 1 (Hep Par 1) and glypican 3 (GPC3)] and cholangiocyte markers [cytokeratin (CK)7 and 19] in tumor tissues was examined by immuno histochemical analysis. RESULTS: In the 16 CHC specimens, the difference in LOH patterns between HCC and ICC was less than 30%, suggesting the same clonal origin of HCC and ICC. Consistent with this finding, immunohistochemical analysis revealed that hepatocyte markers (Hep Par 1 and GPC3) and cholangiocyte markers (CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9% of CHC specimens, suggesting that the two components shared a similar phenotype with hepatic progenitor cells (HPCs). On the contrary, in all 10 SHC cases, the difference in LOH patterns between the HCC and ICC components was greater than 30%, suggesting different clonal origins of HCC and ICC. Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC (P < 0.05). CONCLUSIONS: Our results suggest that the HCC and ICC components of CHC may originate from the same clone, having the potential for dual-directional differentiation similar to HPCs. CHC tended to exhibit the biological behaviors of both HCC and ICC, which may enhance the infiltrative capacity of tumor cells, leading to poor clinical outcomes for patients with CHC. PMID- 27552846 TI - Fc Engineering to Improve the Function of Therapeutic Antibodies. AB - Monoclonal antibodies are currently the most attractive therapeutic modality in a broad range of disease areas, including infectious diseases, autoimmune diseases, and oncology. Fc engineering is one attractive application to maximize the value or overcome the drawbacks of monoclonal antibodies for therapeutic use. With the Fc region, antibodies bind to several types of receptors, such as Fc gamma receptors, a complement receptor, and a neonatal Fc receptor. Through this interaction with the receptors, antibodies demonstrate unique functions, such as antibody-dependent cellular cytotoxicity, antibody- dependent cellular phagocytosis, complement dependent cytotoxicity, agonistic activity, and endosomal recycling. Fc engineering technology is conducted mainly to maximize the receptor-mediated functions of antibodies. Moreover, Fc engineering of the two heavy chains to facilitate heterodimerization is indispensable for generating IgG-like bispecific antibodies that are asymmetric. Fc engineering is also conducted to avoid the undesired properties, such as cytokine release and protease-mediated cleavage of the hinge region, of wild-type antibodies, as well as providing additional functions. Thus, Fc engineering technology is an attractive approach for maximizing the potency and convenience of therapeutic antibodies. This review will cover a variety of Fc engineering technologies that improve the functions of therapeutic antibodies. PMID- 27552847 TI - New Directions for Half-Life Extension of Protein Therapeutics: The Rise of Antibody Fc Domains and Fragments. AB - Protein-based therapeutics has become one of the most rapidly growing and successful drug class in the clinic. However, there are still a number of key challenges that need to be addressed before the full therapeutic potential of protein drugs can be realized. Of note, many biologically active proteins have very short in vivo half-lives, a fact that has greatly hindered their clinical applications. Consequently, several different strategies including polyethylene glycol modification and fusion with Fc or albumin have been developed and implemented to prolong the serum half-life of protein therapeutics. Here we will focus on the recent advances in the development of Fc-based antibody fragments and domains and their potential use as novel half-life-extending fusion partners for protein therapeutics. PMID- 27552845 TI - Improving health related quality of life among rural hypertensive patients through the integrative strategy of health services delivery: a quasi experimental trial from Chongqing, China. AB - BACKGROUND: Integrative strategy of health services delivery has been proven to be effective in economically developed countries, where the healthcare systems have enough qualified primary care providers. However rural China lacks such providers to act as gatekeeper, besides, Chinese rural hypertensive patients are usually of old age, more likely to be exposed to health risk factors and they experience a greater socio-economic burden. All these Chinese rural setting specific features make the effectiveness of integrative strategy of health services in improving health related quality of life among Chinese rural hypertensive patients uncertain. METHODS: In order to assess the impact of integrative strategy of health services delivery on health related quality of life among Chinese rural hypertensive patients, a two-year quasi-experimental trial was conducted in Chongqing, China. At baseline the sample enrolled 1006 hypertensive patients into intervention group and 420 hypertensive patients into control group. Physicians from village clinics, town hospitals and county hospitals worked collaboratively to deliver multidisciplinary health services for the intervention group, while physicians in the control group provided services without cooperation. The quality of life was studied by SF-36 Scale. Blood pressures were reported by town hospitals. The Difference-in-Differences model was used to estimate the differences in SF-36 score and blood pressure of both groups to assess the impact. RESULTS: The study showed that at baseline there was no statistical difference in SF-36 scores between both groups. While at follow-up the intervention group scored higher in overall SF-36, Role Physical, Body Pain, Social Functioning and Role Emotional than the control group. The Difference-in Differences result demonstrated that there were statistical differences in SF-36 total score (p = 0.011), Role Physical (p = 0.027), Social Functioning (p = 0.000), Role Emotional (p = 0.002) between both groups. Integrative services delivery improved the score of SF-36 by 4.591 +/- 1.794, and also improved the score in domains of Role Physical, Social Functioning and Role Emotional by 8.289 +/- 3.753, 9.762 +/- 2.019 and 12.534 +/- 4.083, respectively. CONCLUSION: Patients in the intervention group obtained lower systolic blood pressure and diastolic blood pressure. Integrative strategy of health services delivery improved health related quality of life and blood pressure control among rural Chinese hypertensive patients. TRIAL REGISTRATION: The Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, ChiCTR-OOR 14005563, Registered on 7 June 2011. PMID- 27552849 TI - Costs and outcomes of the German disease management programme (DMP) for chronic obstructive pulmonary disease (COPD)-A large population-based cohort study. AB - INTRODUCTION: To curb costs and improve health outcomes in chronic obstructive pulmonary disease (COPD), a nationwide disease management programme (DMP) was introduced in Germany in 2005. Yet, its effectiveness has not been comprehensively evaluated. OBJECTIVE: To examine the effects of the German COPD DMP over three years on costs and health resource utilisation from the payer perspective, process quality, morbidity and mortality. METHODS: A retrospective, population-based cohort study design is applied, using administrative data. After eliminating differences in observable characteristics between the DMP and the control group with entropy balancing, difference-in-difference estimators were computed to account for time-invariant unobservable heterogeneity. RESULTS: 215,104 individuals were included into the analysis of whom 25,269 were enrolled in the DMP. DMP patients had a reduced mortality hazard ratio (0.89, 95%CI: 0.84 0.94) but incurred excess costs of ?553 per year. DMP enrolees reveal higher healthcare utilisation with larger shares of individuals being hospitalised (3.14%), consulting an outpatient clinic due to exacerbations (11.13%) and pharmaceutical prescriptions (2.78). However, average length of hospitalisation due to COPD fell by 0.49 days, adherence to medication guidelines as well as indicators for morbidity improved. CONCLUSION: The German COPD DMP achieved significant improvements in mortality, morbidity and process quality, but at higher costs. Given the low ICER per life year gained, DMP COPD may constitute a cost-effective option to promote COPD population health. PMID- 27552851 TI - Modeling and simulation of fish swimming with active muscles. AB - Our goal is to reproduce the key features of carangiform swimming by modeling muscle functioning using the notion of active distortions, thus emphasizing the kinematical role of muscle, the generation of movement, rather than the dynamical one, the production of force. This approach, already proposed to model the action of muscles in different contexts, is here tested again for the problem of developing an effective and reliable framework to model and simulate swimming. A proper undulatory movement of a fish-like body is reproduced by defining a pattern of distortions, tuned in both space and time, meant to model the muscles activation which produce the flexural motion of body fish; eventually, interactions with the surrounding water yields the desired thrust. Carangiform swimmers have a relatively inflexible anterior body section and a generally flat, flexible posterior section. Because of this configuration, undulations sent rearward along the body attain a significant amplitude only in the posterior section. We compare the performances of different swimming gaits, and we are able to find some important relations between key parameters such as frequencies, wavelength, tail amplitude, and the achieved swim velocity, or the generated thrust, which summarize the swimming performance. In particular, an interesting relation is found between the Strouhal number and the wavelength of muscles activation. We highlight the muscle function during fish locomotion describing the activation of muscles and the relation between the force production and the shortening-lengthening cycle of muscle. We found a great accordance between results and empirical relations, giving an implicit validation of our models. PMID- 27552850 TI - Characterization of BioPlex network by topological properties. AB - Protein-protein interaction (PPI) networks are emerging as valuable prototypes to study important problems in molecular cellular biology and systems biomedicine. An analysis of the topological properties of a PPI network is very helpful for understanding the function and structure of networks. In this study, we analyzed the topological patterns in the BioPlex network containing interactions among 10,961 proteins; most interactions were previously undocumented. The BioPlex network is a comprehensive map of human protein interactions and represents the first phase of a long-term effort to profile the entire human ORFEOME collection. Similar to other biological networks, we observed that the BioPlex network has several topological properties. We also quantified correlations profiles for the BioPlex network and compared them to randomized versions of the same network. We found that for the BioPlex network, edges between proteins with intermediate degrees were strongly suppressed, whereas edges between low-connected proteins were favored. Finally, the degrees of essential genes were compared with the degrees of non-essential genes and randomly selected proteins. There were no significant differences between the groups. PMID- 27552848 TI - Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study. AB - BACKGROUND: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. METHODS: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged >= 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. RESULTS: Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. CONCLUSIONS: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged >= 60 years with newly diagnosed epilepsy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00175903 ; September 9, 2005. PMID- 27552852 TI - The Impact of Operating Room Noise Upon Communication During Percutaneous Nephrostolithotomy. AB - OBJECTIVE: Equipment and personnel contribute to the overall noise level in the operating room (OR). This study aims to determine intraoperative noise levels during percutaneous nephrostolithotomy (PCNL) and the effects of this noise upon intraoperative communication. METHODS: A PCNL benchtop model was used to measure intraoperative noise and determine its effect upon communication in three progressively increasing sound environments (baseline ambient noise, ambient noise with PCNL equipment, and ambient noise with both PCNL equipment and music). Five trials with 20 different medical words/phrases were spoken by the surgeon and responses were recorded by the first assistant, anesthesiologist, and circulating nurse. In addition, noise levels during PCNL were compared to common environmental noise levels. RESULTS: In the bench top model, noise levels were 53.49 A-weighted decibels (dBA) with ambient noise, 78.79 dBA with equipment in use, and 81.78 dBA with equipment and music. At the ambient noise level, the first assistant, anesthesiologist, and circulator correctly recorded 100%, 100%, and 96% of the words, respectively. The correct response rate by the subjects decreased to 97% (p = 0.208), 81% (p = 0.012), and 56% (p < 0.001) upon addition of PCNL equipment, and 90% (p = 0.022), 48% (p = 0.002), and 13% (p < 0.001) upon addition of music and PCNL equipment in the first assistant, anesthesiologist, and circulator, respectively. In the simulated OR model, PCNL noise level (81.78 dBA) was comparable to a passing freight train at 30 feet (82.2 dBA, p = 0.44). CONCLUSION: Noise pollution decreases effective intraoperative communication during PCNL. It is important for surgeons to understand the effect noise can have on attempted communication to prevent errors due to miscommunication. In addition, methods to decrease intraoperative noise pollution and improve communication in the OR could improve patient safety and outcomes. PMID- 27552853 TI - Family initiated escalation of care for the deteriorating patient in hospital: Family centred care or just "box ticking". AB - Family centred care is a shared belief that a child's emotional and developmental needs are best met when the health system involves the family in planning, delivery and evaluation of care. The important role that families contribute to health care outcomes is emphasised throughout the National Safety and Quality Healthcare Service (NSQHS) Standards. An emerging component is the family's contribution to Rapid Response Systems (RRS) through the early detection of patient clinical deterioration. This initiative has been driven, in part, by a number of high profile paediatric cases where it was identified that healthcare providers did not appropriately respond to families' concerns, resulting in patient deaths. This paper draws together the synergies between family centred care concepts, the NSQHS Standards, and the progress made to date in developing a family initiated process for escalating care with specific reference to paediatric acute care. A number of programs have been developed to guide implementation of family escalation of care. Measures of effectiveness of implementation have mainly focused on policy and process without first understanding barriers or facilitators through engagement with stakeholders and environmental assessment. Two recent reviews have not identified any rigorous attempts to evaluate implementation and only 11 reports are cited across these reviews to date. Evaluation of effectiveness of this complex intervention should take into account process measures of fidelity, dose and reach. There is also a need to assess the impact on families, particularly within a diverse cultural mix. An agreed definition for a paediatric RRS patient outcome measure is essential in evaluating the impact on patient safety and quality. Without this systematic evidence informed knowledge translation approach, then it would appear that progress in implementing family initiated deterioration of condition processes is more about meeting the NSQHS Standards - ticking the box - than genuine engagement with families. PMID- 27552854 TI - Does Yoga Help Patients With Irritable Bowel Syndrome? PMID- 27552855 TI - Graft-Versus-Host Disease Presenting as Anorectal Ulcer. PMID- 27552856 TI - Thalidomide in Refractory Crohn's Disease: Risk-Benefit Ratio. PMID- 27552857 TI - Alterations in Diets of Patients With Nonceliac Gluten Sensitivity Compared With Healthy Individuals. AB - BACKGROUND & AIMS: There is evidence that food components beyond gluten cause symptoms in patients with gluten sensitivity without celiac disease (nonceliac gluten sensitivity [NCGS]). We investigated the diets and nutritional characteristics of patients with NCGS. METHODS: We performed a prospective observational study of 29 patients with NCGS seen at the outpatient clinic for celiac disease and other food intolerances of the University of Salerno in Italy from September 2015 through April 2016. Our study also included 37 control subjects. An experienced dietitian administered a validated food frequency questionnaire (from the European Prospective Investigation into Cancer and Nutrition) to collect information on amounts of common foods consumed. Patients and control subjects also completed the Eating Attitudes Test for diet-related disorders. Patients with NCGS completed the Minnesota Multiphasic Personality Inventory 2-I questionnaire. Differences in frequencies between patients and control subjects were calculated using chi-square test, whereas differences between continuous variables were calculated using Student t test. All tests were 2-tailed with significance level set at P < .05. RESULTS: Comparing the mean value of food daily eaten, we found that patients with NCGS ate smaller amounts of bread, rice, pasta, and cheese than control subjects. The patients ingested lower mean amounts of carbohydrates (P < .001), proteins (P = .001), fiber (P = .002), and polyunsaturated fatty acids (P = .01). More patients with NCGS than control subjects reported avoiding fruit, vegetables, milk, and dairy products, as well as snacks and mixed spices that are traditionally considered unsafe for people with gastrointestinal symptoms. Seven patients and 3 control subjects with scores >=20 on the Eating Attitudes Test were invited for a psychological consultation; it did not confirm the presence of altered eating behaviors. Patients with NCGS had scores >65 from the Minnesota Multiphasic Personality Inventory, indicating a high level of concern for their health. CONCLUSIONS: In an observational study, we found that patients with NCGS eat different foods than healthy individuals; patients consume lower levels of proteins, carbohydrates, fiber, and polyunsaturated fatty acids. Their diets should be routinely analyzed and possibly corrected to avoid nutritional deficiencies. PMID- 27552858 TI - Diet of Amazon river turtles (Podocnemididae): a review of the effects of body size, phylogeny, season and habitat. AB - Amazon rivers can be divided into three groups (black, white and clear waters) according to the origin of their sediment, dissolved nutrient content, and vegetation. White water rivers have high sediment loads and primary productivity, with abundant aquatic and terrestrial plant life. In contrast, black water rivers are acid and nutrient-poor, with infertile floodplains that support plant species exceptionally rich in secondary chemical defences against herbivory. In this study, we reviewed available information on the diet of Amazon sideneck river turtles (Family Podocnemididae). Our aim was to test the relationship between water type and diet of podocnemidids. We also took into account the effects of season, size, age, sex and phylogeny. Based on our review, turtles of this family are primarily herbivorous but opportunistic, consuming from 46 to 99% (percent volume) of vegetable matter depending on species, sex, season and location. There was no significant correlation between the maximum carapace size of a species and vegetable matter consumed. When the available information on diet, size and habitat was arranged on the podocnemidid phylogeny, no obvious evolutionary trend was evident. The physicochemical properties of the inhabited water type indirectly influence the average volume of total vegetable matter consumed. Species with no specialised stomach adaptations for herbivory consumed smaller amounts of hard to digest vegetable matter (i.e. leaves, shoots and stems). We propose that turtles with specialized digestive tracts may have an advantage in black water rivers where plant chemical defences are more common. Despite limitations of the published data our review highlights the overall pattern of diet in the Podocnemididae and flags areas where more studies are needed. PMID- 27552859 TI - Implementing the US air quality standard for PM2.5 worldwide can prevent millions of premature deaths per year. AB - BACKGROUND: Air pollution by fine aerosol particles is among the leading causes of poor health and premature mortality worldwide. The growing awareness of this issue has led several countries to implement air pollution legislation. However, populations in large parts of the world are still exposed to high levels of ambient particulate pollution. The main aim of this work is to evaluate the potential impact of implementing current air quality standards for fine particulate matter (PM2.5) in the European Union (EU), United States (US) and other countries where PM2.5 levels are high. METHODS: We use a high-resolution global atmospheric chemistry model combined with epidemiological concentration response functions to investigate premature mortality attributable to PM2.5 in adults >=30 years and children <5 years. We perform sensitivity studies to estimate the reductions in mortality that could be achieved if the PM2.5 air quality standards of the EU and US and other national standards would be implemented worldwide. RESULTS: We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand per year. For the 28 EU member states we estimate 173 thousand and for the United States 52 thousand premature deaths in 2010. Based on sensitivity analysis, applying worldwide the EU annual mean standard of 25 MUg/m(3) for PM2.5 could reduce global premature mortality due to PM2.5 exposure by 17 %; while within the EU the effect is negligible. With the 2012 revised US standard of 12 MUg/m(3) premature mortality by PM2.5 could drop by 46 % worldwide; 4 % in the US and 20 % in the EU, 69 % in China, 49 % in India and 36 % in Pakistan. These estimates take into consideration that about 22 % of the global PM2.5 related mortality cannot be avoided due to the contribution of natural PM2.5 sources, mainly airborne desert dust and PM2.5 from wild fires. CONCLUSIONS: Our results reflect the need to adopt stricter limits for annual mean PM2.5 levels globally, like the US standard of 12 MUg/m(3) or an even lower limit to substantially reduce premature mortality in most of the world. PMID- 27552860 TI - Droplet dynamics in rotating flows. AB - This paper deals with investigations of droplet dynamics in rotating flows. In many previous studies droplet dynamics was analyzed in simple unidirectional flows. To fill this gap, the focus of this study is an overview on investigations of droplet dynamics in a complex rotating flow. A Lattice Boltzmann Method with high potential in simulation of two-phase unsteady flows is applied to simulate the physics of the problem in a lid-driven cavity. In spite of its simple geometry, there is a complex rotating flow field containing different vortices and shear regions. The Reynolds number based on the cavity length scale and the upper wall velocity, ReL, is considered to be 1000. We discuss here effects of different parameters such as: density ratios (1, 5, 10, 100, and 1000), droplet sizes (D/L=0.097, 0.114, 0.131 and 0.2), and droplet initial positions (1/8, 2/8, and 3/8 of the cavity length, L, out of center). The results are discussed in terms of global flow physics and its interaction with the droplet, drop deformation during its motion along with the main flow, and droplet trajectories. It is shown that there are strong interactions between the droplet and the main carrying flow. During motion, the droplets pass through different flow regions containing acceleration/deceleration zones. Consequently, the droplets experience different shear forces resulting in stretching, shrinking, rotating and dilatation which all contribute to the dynamics of the droplet. PMID- 27552900 TI - Combining HLA-DRB1-DQB1 and Mycobacterium Avium Subspecies Paratubercolosis (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors? AB - BACKGROUND: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. METHODS: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1 DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. RESULTS: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). CONCLUSIONS: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP. PMID- 27552902 TI - Editorial (Thematic Issue: Perspectives and Challenges in Rational Exploitation of Phytochemicals in Cure, Control and Management of Diseases). PMID- 27552901 TI - Mechanism of action of herbs and their active constituents used in hair loss treatment. AB - This article discusses the mechanisms via topically applied products containing herbs and their active constituents affect the hair growth process. It was reported that the mechanisms involving (1) insulin-like growth factor-I (IGF-I), (2) vascular endothelial growth factor (VEGF), (3) epidermal growth factor (EGF), (4) fibroblast growth factor 2 (FGF-2), (5) endothelial nitric oxide synthase (eNOS), (6) Wnt/beta-catenin signalling pathway, (7) prostaglandin E (PGE), (8) prostaglandin F (PGF) stimulate hair growth, whereas the mechanisms engaging (1) 5alpha-reductase and dihydrotestosterone (DHT), (2) transforming growth factor beta (TGF-beta), (3) fibroblast growth factor 5 (FGF-5), (4) prostaglandin D2 (PGD2) inhibit hair growth. The knowledge summarized in the paper may be an inspiration to create new preparations for the treatment of hair loss. PMID- 27552903 TI - Doxycycline hyclate-loaded bleached shellac in situ forming microparticle for intraperiodontal pocket local delivery. AB - Bleached shellac (BS) is a water-insoluble polyester resin made up of sesquiterpenoid acids esterified with hydroxy aliphatic acids. In this study, BS dissolved in N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO) and 2 pyrrolidone was used as the internal phase of oil in oil emulsion using olive oil emulsified with glyceryl monostearate (GMS) as the external phase of in situ forming microparticles (ISM). Doxycycline hyclate (DH)-loaded BS ISMs were tested for emulsion stability, viscosity, rheology, transformation into microparticles, syringeability, drug release, surface topography, in vitro degradation and antimicrobial activities against Staphylococcus aureus, Streptococcus mutans and Porphyromonas gingivalis. All emulsions exhibited pseudoplastic flow and notably low syringeability force. Slower transformation from emulsion into microparticles of ISM prepared with 2-pyrrolidone was owing to slower solvent exchange of this solvent which promoted less porous structure of obtained BS matrix microparticles. The system containing 2-pyrrolidone exhibited a higher degradability than that prepared with DMSO. Developed DH-loaded BS ISMs exhibited a sustainable drug release for 47days with Fickian diffusion and effectively inhibited P. gingivalis, S. mutans and S. aureus. Therefore a DH-loaded BS ISM using olive oil containing GMS as the external phase and 2-pyrrolidone as a solvent was a suitable formulation for periodontitis treatment. PMID- 27552904 TI - Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol. AB - To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232+/-0.021cm/s to 0.508+/-0.038cm/s in the presence of brilliant blue and to 0.405+/-0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation. PMID- 27552905 TI - Experimental and in silico investigations of organic phosphates and phosphonates sorption on polymer-ceramic monolithic materials and hydroxyapatite. AB - A method based on experimental and in silico evaluations for investigating interactions of organic phosphates and phosphonates with hydroxyapatite was developed. This quick and easy method is used for determination of differences among organophosphorus compounds of various structures in their mineral binding affinities. Empirical sorption evaluation was carried out using liquid chromatography with tandem mass spectrometry or UV-VIS spectroscopy. Raman spectroscopy was used to confirm sorption of organic phosphates and phosphonates on hydroxyapatite. Polymer-ceramic monolithic material and bulk hydroxyapatite were applied as sorbent materials. Furthermore, a Polymer-ceramic Monolithic In Needle Extraction device was used to investigate both sorption and desorption steps. Binding energies were computed from the fully optimised structures utilising Density Functional Theory (DFT) at B3LYP/6-31+G(d,p) level. Potential pharmacologic and toxic effects of the tested compounds were estimated by the Prediction of the Activity Spectra of Substances using GeneXplain software. PMID- 27552906 TI - Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort((r)) Turbuhaler((r)) dry powder fixed combination aerosol drug. AB - One of the most widespread dry powder fixed combinations used in asthma and chronic obstructive pulmonary disease (COPD) management is Symbicort((r)) Turbuhaler((r)). The aim of this study was to simulate the deposition distribution of both components of this drug within the airways based on realistic airflow measurements. Breathing parameters of 25 healthy adults (11 females and 14 males) were acquired while inhaling through Turbuhaler((r)). Individual specific emitted doses and particle size distributions of Symbicort((r)) Turbuhaler((r)) were determined. A self-developed particle deposition model was adapted and validated to simulate the deposition of budesonide (inhaled corticosteroid; ICS) and formoterol (long acting beta2 agonist; LABA) in the upper airways and lungs of the healthy volunteers. Based on current simulations the emitted doses varied between 50.4% and 92.5% of the metered dose for the ICS, and between 38% and 96.1% in case of LABA component depending on the individual inhalation flow rate. This variability induced a notable inter-individual spread of the deposited lung doses (mean: 33.6%, range: 20.4%-48.8% for budesonide and mean: 29.8%, range: 16.4%-42.9% for formoterol). Significant inter-gender differences were also observed. Average lung dose of budesonide was 29.2% of the metered dose for females and 37% for males, while formoterol deposited with 26.4% efficiency for females and 32.5% for males. Present results also highlighted the importance of breath-holding after inhalation of the drug. About a half of the total lung deposition occurred during breath-hold at 9.6s average breath-hold time. Calculated depositions confirmed appropriate lung deposition of Symbicort((r)) Turbuhaler((r)) for both genders, however more effort for optimal inhalation technique is advised for persons with low vital capacity. This study demonstrated the possibility of personalized prediction of airway deposition of aerosol drugs by numerical simulations. The methodology developed in this study will be applicable also to other marketed drugs in the future. PMID- 27552907 TI - Designing the angiogenic inhibitor for brain tumor via disruption of VEGF and IL17A expression. AB - Glioblastoma multiforme is a highly malignant, heterogenic, and drug resistant tumor. The blood-brain barrier (BBB), systemic cytotoxicity, and limited specificity are the main obstacles in designing brain tumor drugs. In this study a computational approach was used to design brain tumor drugs that could downregulate VEGF and IL17A in glioblastoma multiforme type four. Computational screening tools were used to evaluate potential candidates for antiangiogenic activity, target binding, BBB permeability, and ADME physicochemical properties. Additionally, in vitro cytotoxicity, migration, invasion, tube formation, apoptosis, ROS and ELISA assays were conducted for molecule 6 that was deemed most likely to succeed. The efflux ratio of membrane permeability and calculated docking scores of permeability to glycoproteins (P-gps) were used to determine the BBB permeability of the molecules. The results showed BBB permeation for molecule 6, with the predicted efficiency of 0.55kcal/mol and binding affinity of -37kj/mol corresponding to an experimental efflux ratio of 0.625 and predicted 15kj/mol of binding affinity for P-gps. Molecule 6 significantly affected the angiogenesis pathways by 2-fold downregulation of IL17A and VEGF through inactivation of active sites of HSP90 (predicted binding: -37kj/mol, predicted efficiency: 0.55kcal/mol) and p23 (predicted binding: 12kj/mol, predicted efficiency: 0.17kcal/mol) chaperon proteins. Additionally, molecule 6 activated the 17.38% relative fold of ROS level at 18.3MUg/mL and upregulated the caspase which lead the potential synergistic apoptosis through the antiangiogenic activity of molecule 6 and thereby the highly efficacious anticancer upshot. The results indicate that the binding of the molecules to the therapeutic target is not essential to produce a lethal effect on cancer cells of the brain and that antiangiogenic efficiency is much more important. PMID- 27552908 TI - InterACTIVE Interpreted Interviews (I3): A multi-lingual, mobile method to examine the neighbourhood environment with older adults. AB - The global population is aging and older adults overwhelmingly wish to age in place. A positive neighbourhood context is crucial for the wellbeing of older adults. The ability to age in place is predicated on mobility; mobility is the capacity to move oneself around the home and community using a variety of modes. Segments of the population have been entirely overlooked within the mobility and built environment literature; we know surprisingly little about foreign-born older adults (FBOAs). We sought to understand the impact of the neighbourhood environment on the mobility and physical activity of FBOAs. To do so we endeavoured to develop an interview tool that would allow us to interact with the environment alongside, or through the eyes of, our participants. This article outlines lessons learned following design and implementation of an interview approach that we conducted with FBOAs -- "InterACTIVE Interpreted Interviews (I3)". We used the interACTIVE interview approach in a large mixed-method study on FBOA mobility in Vancouver, Canada. All aspects of the study were offered in Hindi, Punjabi, Cantonese, Mandarin and English, with the aid of professional interpreters. Twenty FBOAs completed in-depth qualitative interviews. Of these, thirteen completed the mobile, interACTIVE interview. The interACTIVE interview consisted of a neighbourhood walk, guided by the participant. Our approach integrated elements of participant observation, researcher participation, and unstructured interviewing to enrich discussions with participants. The interACTIVE approach deepened our understanding of neighbourhood context and allowed researchers and participants to overcome issues inherent in language interpretation. We were able to overcome concerns of privacy, safety and comfort to successfully implement this observational tool and recommend it as an attractive, alternative approach for those conducting studies with FBOAs. PMID- 27552909 TI - A new method for assessing plant lodging and the impact of management options on lodging in canola crop production. AB - Lodging, defined as the permanent displacement of aboveground parts, is a common problem to cause yield loss, deterioration in seed quality and difficult to harvest in canola (Brassica napus L.) crop production. This study aimed to develop a method for assessing crop lodging, to examine how agronomic practices affected the relationships between root lodging and electrical capacitance traits. Canola plants were more susceptible to root lodging than stem lodging. The electrical measurements were more closely related with anchorage strength (Sp) than stem bending strength (Ss). Among the three electrical measurements, the root capacitance (C) displayed the most consistent and significant relationships with Sp in all three field experiments (R(2) = 0.88-0.56; P <= 0.01). This study indicates that the risk of lodging can be reduced by using appropriate management practices and variety selection. Enhancing root Sp was advocated as a priority over enhancing stem Ss in cultivar improvement. Electrical measurements, especially of root C, can be considered as a non invasive technique that could partially replace the intrusive methods used for the in situ assessment of lodging resistance among various agronomic practices or can be applied in breeding programs for selecting genotypes with high yield potentials and strong Sp values. PMID- 27552910 TI - New Developments in Clinical Bacteriology Laboratories. AB - There are a number of changes underway in modern clinical bacteriology laboratories. Panel-based molecular diagnostics are now available for numerous applications, including, but not limited to, detection of bacteria and select antibacterial resistance markers in positive blood culture bottles, detection of acute gastroenteritis pathogens in stool, and detection of selected causes of acute meningitis and encephalitis in the cerebrospinal fluid. Today, rapid point of-care nucleic acid amplification tests are bringing the accuracy of sophisticated molecular diagnostics closer to patients. A proteomic technology, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, is enabling rapid, accurate, and cost-effective identification of bacteria, as well as fungi, recovered in cultures. Laboratory automation, common in chemistry laboratories, is now available for clinical bacteriology laboratories. Finally, there are several technologies under development, such as rapid phenotypic antimicrobial susceptibility testing, whole-genome sequencing, and metagenomic analysis for the detection of bacteria in clinical specimens. It is helpful for clinicians to be aware of the pace of new development in their bacteriology laboratory to enable appropriate test ordering, to enable test interpretation, and to work with their laboratories and antimicrobial stewardship programs to ensure that new technology is implemented to optimally improve patient care. PMID- 27552912 TI - What incentives influence employers to engage in workplace health interventions? AB - BACKGROUND: To achieve a sustainable working life it is important to know more about what could encourage employers to increase the use of preventive and health promotive interventions. The objective of the study is to explore and describe the employer perspective regarding what incentives influence their use of preventive and health promotive workplace interventions. METHOD: Semi-structured focus group interviews were carried out with 20 representatives from 19 employers across Sweden. The economic sectors represented were municipalities, government agencies, defence, educational, research, and development institutions, health care, manufacturing, agriculture and commercial services. The interviews were transcribed verbatim and the data were analysed using latent content analysis. RESULTS: Various incentives were identified in the analysis, namely: "law and provisions", "consequences for the workplace", "knowledge of worker health and workplace health interventions", "characteristics of the intervention", "communication and collaboration with the provider". The incentives seemed to influence the decision-making in parallel with each other and were not only related to positive incentives for engaging in workplace health interventions, but also to disincentives. CONCLUSIONS: This study suggests that the decision to engage in workplace health interventions was influenced by several incentives. There are those incentives that lead to a desire to engage in a workplace health intervention, others pertain to aspects more related to the intervention use, such as the characteristics of the employer, the provider and the intervention. It is important to take all incentives into consideration when trying to understand the decision-making process for workplace health interventions and to bridge the gap between what is produced through research and what is used in practice. PMID- 27552911 TI - Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis. AB - Optineurin (OPTN) mutations cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and glaucoma. Although the ALS-associated E478G mutation in the UBAN domain of OPTN reportedly abolishes its NF-kappaB suppressive activity, the precise molecular basis in ALS pathogenesis still remains unclear. Here we report that the OPTN-UBAN domain is crucial for NF kappaB suppression. Our crystal structure analysis reveals that OPTN-UBAN binds linear ubiquitin with homology to NEMO. TNF-alpha-mediated NF-kappaB activation is enhanced in OPTN-knockout cells, through increased ubiquitination and association of TNF receptor (TNFR) complex I components. Furthermore, OPTN binds caspase 8, and OPTN deficiency accelerates TNF-alpha-induced apoptosis by enhancing complex II formation. Immunohistochemical analyses of motor neurons from OPTN-associated ALS patients reveal that linear ubiquitin and activated NF kappaB are partially co-localized with cytoplasmic inclusions, and that activation of caspases is elevated. Taken together, OPTN regulates both NF-kappaB activation and apoptosis via linear ubiquitin binding, and the loss of this ability may lead to ALS. PMID- 27552913 TI - Vitamin D status in Egyptian euthyroid multinodular non-toxic goiter patients and its correlation with TSH levels. AB - BACKGROUND AND AIM: Although the prevalence of MNG is widespread throughout the world, its pathogenesis is poorly understood, and the complex interactions of both genetic predisposition and the individuals' environment are likely. However, to the best of our knowledge, it remains unknown whether there is a relationship between vitamin D status and prevalence or pathogenesis of euthyroid MNG. Therefore, the goal of the present study was determination of vitamin D status in euthyroid MNG as well as exploration of the correlation between vitamin D status & TSH levels. METHODS: A total of 77 patients diagnosed with euthyroid MNG and 50 subjects without goiter were matched according to age, weight and BMI as control group in this case control study. RESULTS: We found that patients with euthyroid MNG had statistically significant lower mean of [25(OH)D] (24.21+/-8.68ng/mL) in comparison with its mean in control subjects (28.37+/-10.91ng/mL, P value=0.019). The 28 sufficient vitamin D MNG patients had statistically significant lower level of TSH than 49 insufficient vitamin D MNG patients. Vitamin D and TSH levels correlate with vitamin D levels in MNG patients in Pearson correlation. Also 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients in regression analysis. CONCLUSIONS: Patients with euthyroid MNG have lower levels of vitamin D and TSH levels correlate with vitamin D levels in euthyroid MNG patients. In addition, 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients. We recommend hypovitaminosis D evaluation and correction in patients with MNG. PMID- 27552914 TI - A-type lamin-dependent homo-oligomerization for pY19-Caveolin-2 to function as an insulin-response epigenetic regulator. AB - Association of Caveolin-2 in the inner nuclear membrane specifically with A-type lamin is crucial for the maintenance of its Tyr-19 phosphorylation to promote insulin-response epigenetic activation at the nuclear periphery. Here, we identify that pY19-Caveolin-2 in the inner nuclear membrane exists as homo oligomeric forms and the A-type lamin is required for sustenance of its oligomeric status. Oligomerization-defective and hence pY19-dephosphorylated monomeric Caveolin-2 in the inner nuclear membrane is unable to carry out Caveolin-2-mediated epigenetic activation of Egr-1 and JunB genes and transactivation of Elk-1 and STAT3 in response to insulin. The homo-oligomeric pY19-Caveolin-2 localizes in and recruits epigenetic modifiers to the A-type lamin-enriched inner nuclear membrane microdomain for the epigenetic activation. Our data show that A-type lamin-dependent Caveolin-2 homo-oligomerization in the inner nuclear membrane microdomain is a precondition for pY19-Caveolin-2-mediated insulin-response epigenetic activation at the nuclear periphery. PMID- 27552915 TI - Nucleosome assembly and disassembly activity of GRWD1, a novel Cdt1-binding protein that promotes pre-replication complex formation. AB - GRWD1 was previously identified as a novel Cdt1-binding protein that possesses histone-binding and nucleosome assembly activities and promotes MCM loading, probably by maintaining chromatin openness at replication origins. However, the molecular mechanisms underlying these activities remain unknown. We prepared reconstituted mononucleosomes from recombinant histones and a DNA fragment containing a nucleosome positioning sequence, and investigated the effects of GRWD1 on them. GRWD1 could disassemble these preformed mononucleosomes in vitro in an ATP-independent manner. Thus, our data suggest that GRWD1 facilitates removal of H2A-H2B dimers from nucleosomes, resulting in formation of hexasomes. The activity was compromised by deletion of the acidic domain, which is required for efficient histone binding. In contrast, nucleosome assembly activity of GRWD1 was not affected by deletion of the acidic domain. In HeLa cells, the acidic domain of GRWD1 was necessary to maintain chromatin openness and promote MCM loading at replication origins. Taken together, our results suggest that GRWD1 promotes chromatin fluidity by influencing nucleosome structures, e.g., by transient eviction of H2A-H2B, and thereby promotes efficient MCM loading at replication origins. PMID- 27552916 TI - The ganglioside GM1 interacts with the serotonin1A receptor via the sphingolipid binding domain. AB - Glycosphingolipids are minor yet essential components of eukaryotic cell membranes and are involved in a variety of cellular processes. Although glycosphingolipids such as GM1 have been previously reported to influence the function of G protein-coupled receptors (GPCRs), the molecular mechanism remains elusive. In this paper, we have explored the interaction of GM1 with the serotonin1A receptor, an important neurotransmitter receptor that belongs to the GPCR family. To examine the molecular basis of the interaction of GM1 with the serotonin1A receptor, we performed a series of coarse-grain molecular dynamics simulations of the receptor embedded in membrane bilayers containing GM1. Our results show that GM1 interacts with the serotonin1A receptor predominantly at the extracellular loop 1 and specifically at the sphingolipid binding domain (SBD). The SBD motif consists of a characteristic combination of aromatic, basic and turn-inducing residues, and is evolutionarily conserved in case of the serotonin1A receptor. The interaction of the SBD site with GM1 appears to stabilize a 'flip-out' conformation in which W102 of the extracellular loop 1 flips out from the central lumen of the receptor toward the membrane. The population of the 'flip-out' conformation is increased in the presence of cholesterol. Our data strongly suggest that a direct interaction between GM1 and the SBD site of the serotonin1A receptor may occur in vivo. In view of the reported role of GM1 and the serotonin1A receptor in neurodegenerative diseases, GM1-receptor interaction assumes significance in the context of malfunctioning of neuronal GPCRs under such conditions. PMID- 27552917 TI - The Role of Prostate Apoptosis Response-4 (Par-4) in Mycobacterium tuberculosis Infected Macrophages. AB - Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein that forms a complex with glucose-regulated protein 78 (GRP78) to induce apoptosis. Previously, we reported that ER stress-induced apoptosis is a critical host defense mechanism against Mycobacterium tuberculosis (Mtb). We sought to understand the role of Par-4 during ER stress-induced apoptosis in response to mycobacterial infection. Par-4 and GRP78 protein levels increased in response Mtb (strain: H37Ra) infection. Furthermore, Par-4 and GRP78 translocate to the surface of Mtb H37Ra-infected macrophages and induce apoptosis via caspase activation. NF-kappaB activation, Mtb-mediated ER stress, and Par-4 production were significantly diminished in macrophages with inhibited ROS production. To test Par-4 function during mycobacterial infection, we analyzed intracellular survival of Mtb H37Ra in macrophages with Par-4 overexpression or knockdown. Mtb H37Ra growth was significantly reduced in Par-4 overexpressing macrophages and increased in knockdown macrophages. We also observed increased Par-4, GRP78, and caspases activation in Bacillus Calmette-Guerin (BCG)-infected prostate cancer cells. Our data demonstrate that Par-4 is associated with ER stress-induced apoptosis resulting in reduced intracellular survival of mycobacteria. BCG treatment increases Par-4-dependent caspase activation in prostate cancer cells. These results suggest ER stress-induced Par-4 acts as an important defense mechanism against mycobacterial infection and regulates cancer. PMID- 27552919 TI - SoxE factors: Transcriptional regulators of neural differentiation and nervous system development. AB - Sox8, Sox9 and Sox10 represent the three vertebrate members of the SoxE subclass of high-mobility-group domain containing Sox transcription factors. They play important roles in the peripheral and central nervous systems as regulators of stemness, specification, survival, lineage progression, glial differentiation and homeostasis. Functions are frequently overlapping, but sometimes antagonistic. SoxE proteins dynamically interact with transcriptional regulators, chromatin changing complexes and components of the transcriptional machinery. By establishing regulatory circuits with other transcription factors and microRNAs, SoxE proteins perform divergent functions in several cell lineages of the vertebrate nervous system, and at different developmental stages in the same cell lineage. The underlying molecular mechanisms are the topic of this review. PMID- 27552920 TI - The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair. AB - In addition to their established roles in host defence, Toll-like Receptors (TLRs) have emerging roles in control of homeostasis, injury and wound repair. The dsRNA-sensing receptor, TLR3, has been particularly implicated in such processes in several different tissues including the skin, intestine and liver, as well as in the control of reparative mechanisms in the brain, heart and kidneys, following ischemia reperfusion injury. In this review, we provide an overview of TLR3 signalling and functions in inflammation, tissue damage and repair processes, as well as therapeutic opportunities that may arise in the future from knowledge of such pathways. PMID- 27552918 TI - Molecular mechanisms of Sox transcription factors during the development of liver, bile duct, and pancreas. AB - The liver and pancreas are the prime digestive and metabolic organs in the body. After emerging from the neighboring domains of the foregut endoderm, they turn on distinct differentiation and morphogenesis programs that are regulated by hierarchies of transcription factors. Members of SOX family of transcription factors are expressed in the liver and pancreas throughout development and act upstream of other organ-specific transcription factors. They play key roles in maintaining stem cells and progenitors. They are also master regulators of cell fate determination and tissue morphogenesis. In this review, we summarize the current understanding of SOX transcription factors in mediating liver and pancreas development. We discuss their contribution to adult organ function, homeostasis and injury responses. We also speculate how the knowledge of SOX transcription factors can be applied to improve therapies for liver diseases and diabetes. PMID- 27552921 TI - Systems heterogeneity: An integrative way to understand cancer heterogeneity. AB - The concept of systems heterogeneity was firstly coined and explained in the Special Issue, as a new alternative to understand the importance and complexity of heterogeneity in cancer. Systems heterogeneity can offer a full image of heterogeneity at multi-dimensional functions and multi-omics by integrating gene or protein expression, epigenetics, sequencing, phosphorylation, transcription, pathway, or interaction. The Special Issue starts with the roles of epigenetics in the initiation and development of cancer heterogeneity through the interaction between permanent genetic mutations and dynamic epigenetic alterations. Cell heterogeneity was defined as the difference in biological function and phenotypes between cells in the same organ/tissue or in different organs, as well as various challenges, as exampled in telocytes. The single cell heterogeneity has the value of identifying diagnostic biomarkers and therapeutic targets and clinical potential of single cell systems heterogeneity in clinical oncology. A number of signaling pathways and factors contribute to the development of systems heterogeneity. Proteomic heterogeneity can change the strategy and thinking of drug discovery and development by understanding the interactions between proteins or proteins with drugs in order to optimize drug efficacy and safety. The association of cancer heterogeneity with cancer cell evolution and metastasis was also overviewed as a new alternative for diagnostic biomarkers and therapeutic targets in clinical application. PMID- 27552922 TI - The HIV/AIDS epidemic among young people in China between 2005 and 2012: results of a spatial temporal analysis. AB - OBJECTIVES: Despite a recent increase in the HIV/AIDS epidemic among young people in China, youth-specific HIV data are limited. METHODS: In total, 56 621 individuals with HIV/AIDS, aged 15-24 years, registered in the Case Reporting System of China between 2005 and 2012 and having complete spatial information were included in the present analysis. Spatial autocorrelation (general and local) and space-time scanning were performed using the ArcGIS 10.2 and SaTScan 9.3 software, respectively. RESULTS: During 2005-2012, the number of reported HIV/AIDS cases and the proportion of HIV cases increased while the proportion of AIDS cases decreased. Sexual contact became the predominant route of transmission in later years. Spatial analysis showed marked geographical variations in HIV infection among young people throughout China during 2005-2012. The number of new hotspots increased over time. They were mainly localized to southeastern coastal areas, southwestern frontier provinces or autonomous regions (of Guangxi, Yunnan and Sichuan) and Beijing municipality. Later these hotspots disappeared and new hotspots were found in the northeast of the country. Significant clusters of HIV positive cases were identified in three different time periods, which indicated high HIV transmission among young Chinese people in the recent past. The risk of HIV infection was highest in the first cluster (2009-2012; this cluster was the largest in size) covering the provinces of Guizhou and Yunnan, the Chongqing municipality, Guangxi, and the province of Sichuan. The second cluster (2010 2012) was mostly located in Shanghai, South Jiangsu, Zhejiang and South Anhui, while the third cluster (2010-2012) was located in Beijing and Tianjin. CONCLUSIONS: Target-specific comprehensive behavioural interventions are urgently needed to contain the HIV epidemic among young people. PMID- 27552923 TI - Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source. AB - BACKGROUND: Cells constantly adapt to changes in their environment. When environment shifts between conditions that were previously encountered during the course of evolution, evolutionary-programmed responses are possible. Cells, however, may also encounter a new environment to which a novel response is required. To characterize the first steps in adaptation to a novel condition, we studied budding yeast growth on xylulose, a sugar that is very rarely found in the wild. RESULTS: We previously reported that growth on xylulose induces the expression of amino acid biosynthesis genes in multiple natural yeast isolates. This induction occurs despite the presence of amino acids in the growth medium and is a unique response to xylulose, not triggered by naturally available carbon sources. Propagating these strains for ~300 generations on xylulose significantly improved their growth rate. Notably, the most significant change in gene expression was the loss of amino acid biosynthesis gene induction. Furthermore, the reduction in amino-acid biosynthesis gene expression on xylulose was tightly correlated with the improvement in growth rate, suggesting that internal depletion of amino-acids presented a major bottleneck limiting growth in xylulose. CONCLUSIONS: We discuss the possible implications of our results for explaining how cells maintain the balance between supply and demand of amino acids during growth in evolutionary 'familiar' vs. 'novel' conditions. PMID- 27552924 TI - Spherical Polyolefin Particles from Olefin Polymerization in the Confined Geometry of Porous Hollow Silica Particles. AB - Porous hollow silica particles (HSPs) are presented as new templates to control the product morphology in metallocene-catalyzed olefin polymerization. By selectively immobilizing catalysts inside the micrometer-sized porous hollow silica particles, the high hydraulic forces resulting from polymer growth within the confined geometries of the HSPs cause its supporting shell to break up from the inside. As the shape of the support is replicated during olefin polymerization, perfectly spherical product particles with very narrow size distribution can be achieved by using HSPs exhibiting a monomodal size distribution. Furthermore, the size of the obtained product particles can be controlled not only by the polymerization time but also by the size of the support material. PMID- 27552926 TI - Microenvironment-Responsive Three-Pronged Approach Breaking Traditional Chemotherapy to Target Cancer Stem Cells for Synergistic Inoperable Large Tumor Therapy. AB - Three-pronged nanoparticles (NPs) that can efficiently prohibit the proliferation of large tumor are developed for inoperable large tumor therapy. The NPs achieve spatially and temporally controlled release of drugs in target sites. The NPs induce the apoptosis of differentiated cancer cells, cancer stem cells, and vascular niches simultaneously. Importantly, the three-pronged NPs inhibit the growth of large tumors without recurrence. PMID- 27552925 TI - Characterization of a novel MR-detectable nanoantioxidant that mitigates the recall immune response. AB - In many human diseases, the presence of inflammation is associated with an increase in the level of reactive oxygen species (ROS). The resulting state of oxidative stress is highly detrimental and can initiate a cascade of events that ultimately lead to cell death. Thus, many therapeutic attempts have been focused on either modulating the immune system to lower inflammation or reducing the damaging caused by ROS. Berlin et al. reported the development of a novel nanoantioxidant known as poly(ethylene glycol)-functionalized-hydrophilic carbon clusters (PEG-HCCs). They showed that PEG-HCCs could be targeted to cancer cells, utilized as a drug delivery vector, and can even be visualized ex vivo. Our work here furthers this work and characterizes Gd-DTPA conjugated PEG-HCCs and explores the potential for in vivo tracking of T cells in live mice. We utilized a mouse model of delayed-type hypersensitivity (DTH) to assess the immunomodulatory effects of PEG-HCCs. The T1 -agent Gd-DTPA was then conjugated to the PEG-HCCs and T1 measurements, and T1 -weighted MRI of the modified PEG HCCs was done to assess their relaxivity. We then assessed if PEG-HCCs could be visualized both ex vivo and in vivo within the mouse lymph node and spleen. Mice treated with PEG-HCCs showed significant improvements in the DTH assay as compared to the vehicle (saline)-treated control. Flow cytometry demonstrated that splenic T cells are capable of internalizing PEG-HCCs whereas fluorescent immunohistochemistry showed that PEG-HCCs are detectable within the cortex of lymph nodes. Finally, our nanoantioxidants can be visualized in vivo within the lymph nodes and spleen of a mouse after addition of the Gd-DTPA. PEG-HCCs are internalized by T cells in the spleen and can reduce inflammation by suppression of a recall immune response. PEG-HCCs can be modified to allow for both in vitro and in vivo visualization using MRI. (c) 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID- 27552927 TI - Suicide Risk Screening Tools and the Youth Population. AB - TOPIC: The use of suicide risk screening tools is a critical component of a comprehensive approach to suicide risk assessment. Since nurses frequently spend more time with patients than any other healthcare professional, they are in key positions to detect and prevent suicidal behavior in youth. PURPOSE: To inform nurses about suicide risk screening tools for the youth population. Suicide risk screening tools are research-based standardized instruments that are used to identify people who may be at risk for suicide. SOURCES USED: A literature search was performed using the Athabasca University Library Resource, the databases of the Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, and Google Scholar. CONCLUSIONS: Nurses are cautioned to utilize suicide risk screening tools as only part of the suicide risk assessment in youth populations and avoid the danger of relying on tools that may result in a blind application of evidence to the detriment of clinical experience and judgement. PMID- 27552928 TI - Tyrosine phosphorylation and protein degradation control the transcriptional activity of WRKY involved in benzylisoquinoline alkaloid biosynthesis. AB - Benzylisoquinoline alkaloids (BIQ) are among the most structurally diverse and pharmaceutically valuable secondary metabolites. A plant-specific WRKY-type transcription factor, CjWRKY1, was isolated from Coptis japonica and identified as a transcriptional activator of BIQ biosynthesis. However, the expression of CjWRKY1 gene alone was not sufficient for the activation of genes encoding biosynthetic enzymes. Here, we report the importance of post-translational regulation of CjWRKY1 in BIQ biosynthesis. First, we detected the differential accumulation of CjWRKY1 protein in two cell lines with similar CjWRKY1 gene expression but different levels of accumulated alkaloids. Further investigation of the WRKY protein identified the phosphorylation of the WRKYGQK core domain at Y115. The CjWRKY(Y115E) phosphorylation-mimic mutant showed loss of nuclear localization, DNA-binding activity, and transactivation activity compared to wild type CjWRKY1. Rapid degradation of the CjWRKY1 protein was also confirmed following treatment with inhibitors of the 26S proteasome and protease inhibitors. The existence of two independent degradation pathways as well as protein phosphorylation suggests the fine-tuning of CjWRKY1 activities is involved in the regulation of biosynthesis of BIQs. PMID- 27552929 TI - Influence of plasma cleaning procedure on the interaction between soft tissue and abutments: a randomized controlled histologic study. AB - INTRODUCTION: Plasma application can lead to an improved adhesion between soft tissue and abutments and promotes cell spreading. OBJECTIVE: A triple-blinded randomized controlled clinical trial was performed to in vivo test the effect of cleaning abutment titanium surfaces with plasma of argon on cell adhesion and collagen fiber orientation at an early healing time. MATERIAL AND METHODS: Thirty healthy patients with 30 submerged implants, at the second surgery, randomly received either a specially designed abutment with no additional treatment (as they come from industry; control group, G1) or cleaned by plasma of argon (test group, G2). Two weeks thereafter, a small biopsy including abutment and soft tissues around the abutment was performed. Abutments were analyzed using scanning electron microscopy to assess cell adhesion to the abutment surface. Outcome measures were the following: percentage of area occupied by cells, the presence or absence of cells, aspect of adhered cells, and the presence of contaminants. At the same time, the soft tissue histological analysis evaluated density and orientation of collagen fibers. Statistical analysis was performed using the Kolmogorov-Smirnov normality test and Levene variance homogeneity test. Data were analyzed using a nonparametric ranking test. The associations between the different qualitative variables were studied using Pearson's chi-squared test. The Mann-Whitney U-test (for two independent samples) was applied for quantitative variables. RESULTS: Mean percentages of area occupied by cells were 15.14% (range 2.91-44.27) and 33.75% (range 2.37-68.4) for G1 and G2, respectively. Differences were close to significance (P = 0.089). The proportion of samples presenting adhered cells was homogeneous between the two groups (P = 0.142). In all cases, cells presented a flattened aspect, but not in three cases in the G2; in 17 cases, cells were efficiently adhered, and in 11 cases, cells presented filopodia with no statistical differences between groups (P > 0.05). No case from G2 showed contamination with cocobacteria with statistical differences between groups (P = 0.006). Collagen fiber density was higher in the basal, medial, and coronal area of G2 compared to G1 with a statistical difference in the internal area (P < 0.05). The orientation of the fibers varied according to the coordinate area with oblique fibers predominant in G2 than in G1. CONCLUSION: Plasma of argon may promote cell adhesion and positively influence collagen fiber orientation. A greater sample is necessary to confirm these preliminary results. PMID- 27552930 TI - Commentary on 'Late Survival in Non-operated Patients With Infra-renal Abdominal Aortic Aneurysm'. PMID- 27552931 TI - Single Centre Results of Total Endovascular Repair of Complex Aortic Aneurysms with Custom Made Anaconda Fenestrated Stent Grafts. AB - OBJECTIVE: Fenestrated endovascular aneurysm repair (F-EVAR) has increased the number of patients with aneurysmal disease and a short or no existing neck being eligible for endovascular treatment. The aim of the study is to report experience using the Anaconda fenestrated device with special emphasis on target vessel patency and pitfalls with the device. METHODS: Between 2011 and 2016, 48 F-EVAR procedures were performed in 37 males and 11 females under general anaesthesia using the Anaconda custom made device (CMD). Cerebrospinal fluid drainage was performed in selected cases only. Primary endpoints were 30 day mortality and any stent graft related complications. RESULTS: The median aneurysm diameter was 56 mm. Most of the patients had a juxtarenal aneurysm and six had an aorto-iliac aneurysm. The primary technical success was 94% with three unsuccessful cannulations of reno-visceral arteries, two of which were successfully performed later. In the third patient an open repair was necessary because of occlusion of the main graft. The 30 day mortality was 4% because of colonic ischemia with two thrombotic occlusions of the superior mesenteric artery. Thirty day morbidity included four cases (8%) of acute limb ischemia: one with a complete limb occlusion caused by a torsion of the main body; two cases (4%) of assumed temporary spinal cord ischemia; six cases (12%) of acute renal failure; and 16 endoleaks (33%) (15 type II, 1 type III). During the median 24 months (range 0 53) follow up, three patients died (6%). One had migration of the stent graft, leading to open repair and post-operative multi-organ failure. The second had graft limb occlusion and died because of multi-organ failure caused by post operative thrombosis of the reno-visceral stents. The third patient died of an unrelated cause. Two occlusions of the right renal stent/artery were detected. Moreover, there were three cases (6%) of late partial and seven cases (15%) of total graft limb thrombosis, with one being bilateral. CONCLUSIONS: "Real world" feasibility of the fenestrated Anaconda stent graft is demonstrated with 4% peri operative mortality. Target vessel patency is in line with other series; however, limb thrombosis during follow up is of concern. PMID- 27552932 TI - Editorial on "Delays to Surgery and Procedural Risks Following Carotid Endarterectomy in the UK National Vascular Registry". PMID- 27552934 TI - [Local approval procedures act as a brake on RCTs]. AB - OBJECTIVE: Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. DESIGN: Retrospective, descriptive. METHOD: All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. RESULTS: The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from ? 0-? 1750, and amounted to ? 8575 for all procedures combined. No costs were charged by the majority of the centres. CONCLUSION: The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context. PMID- 27552933 TI - Combined expression of miR-34a and Smac mediated by oncolytic vaccinia virus synergistically promote anti-tumor effects in Multiple Myeloma. AB - Despite great progress made in the treatment of multiple myeloma (MM), it is still incurable. Promising phase II clinical results have been reported recently for oncolytic vaccinia virus (OVV) clinic therapeutics. One reason for this has focused on the critical therapeutic importance of the immune response raised by these viruses. However, few studies have performed their applications as an optimal delivery system for therapeutic gene, especially miRNA in MM. In this study, we constructed two novel OVVs (TK deletion) that express anti-tumor genes, miR-34a and Smac, respectively, in MM cell lines and xenograft model. The results demonstrated that the novel OVV can effectively infect MM cell lines, and forcefully enhance the exogenous gene (miR-34a or Smac) expression. Furthermore, utilization of VV-miR-34a combined with VV-Smac synergistically inhibited tumor growth and induced apoptosis in vitro and in vivo. The underlying mechanism is proposed that blocking of Bcl-2 by VV-miR-34a increases the release of cytochrome c from mitochondria and then synergistically amplifies the antitumor effects of Smac-induced cell apoptosis. Our study is the first to utilize OVV as the vector for miR-34a or Smac expression to treat MM, and lays the groundwork for future clinical therapy for MM. PMID- 27552935 TI - [Tests for alcohol consumption during pregnancy: what biomarkers are suitable?]. AB - Alcohol consumption during pregnancy may lead to severe foetal damage, such as foetal alcohol spectrum disorders. It is known that pregnant women under-report to questionnaires about alcohol consumption. It is therefore necessary to determine alcohol consumption during pregnancy objectively. We present 2 pregnant women with negative urine tests for ethyl glucuronide (EtG) and alcohol. However, analysis of two other biomarkers, phosphatidylethanol (PEth) in blood and fatty acid ethyl esters (FAEE) in meconium, revealed alcohol consumption during pregnancy by both women. Analysis of PEth can yield additional information alongside EtG testing. This is due to the much longer half-life of PEth. Meconium testing for FAEE provides relevant information about alcohol consumption during the second and third trimesters. Both PEth and meconium analysis can help identify women who have consumed alcohol during pregnancy. Appropriate counselling and follow-up can be given to these mothers and their children. PMID- 27552936 TI - [Management of blunt renal trauma in paediatric patients]. AB - - In 90% of children, blunt abdominal trauma is the cause of renal, splenic or hepatic injury or an injury affecting a combination of these organs.- Because children's kidneys are anatomically less protected than those of adults, potential renal injury following direct trauma affecting the child's flank, for example by a handlebar or knee should be considered.- Symptoms of renal trauma include excoriations or haematoma on the flank, a 'seatbelt-sign', macroscopic haematuria and fractures of the ribs and vertebra.- As haematuria does not correlate with the severity of renal injury, all children with persistent haematuria should undergo renal imaging.- Children without abnormalities on Doppler ultrasound examination and without macroscopic haematuria can be discharged from the emergency room.- Conservative management of blunt renal trauma is indicated for all haemodynamically stable children. However, haemodynamically unstable children need to undergo an urgent laparotomy. The routine use of bed rest is only indicated for grade V renal injuries.- A DMSA scan is recommended 6-12 weeks after trauma for grade IV-V renal injury. PMID- 27552937 TI - [Antidepressant guidelines poorly adhered to in young people]. AB - OBJECTIVE: To examine if Dutch physicians adhere to the national guidelines on the treatment of depression in children and adolescents. DESIGN: Retrospective database research. METHOD: Data on children and adolescents aged between 6 and 17 years were selected from the IADB, a Dutch database of filled prescriptions. We examined whether children and adolescents were prescribed fluoxetine as recommended by the guideline, and whether the starting dose was in accordance with the guideline. RESULTS: Of 2942 children and adolescents in whom antidepressant treatment was initiated, the proportion prescribed fluoxetine increased from 10.1% in 1994-2003 to 19.7% in 2010-2014. However, paroxetine (1994-2003) and citalopram (2004-2014) were the most frequently prescribed antidepressants. Starting doses were guideline-concordant in 58% of children, 31% of preadolescents and 16% of adolescents. Sixty percent of all adolescents were prescribed an adult starting dose. CONCLUSION: Guideline adherence was poor. In contrast to the guidelines, physicians preferred citalopram to fluoxetine in children and adolescents with depression. Furthermore, adolescents often received an adult starting dose. These results suggest that dedicated effort is necessary to improve guideline adherence. PMID- 27552938 TI - [An evidence-update on the prospective relationship between childhood sedentary behaviour and biomedical health indicators: a systematic review and meta analysis]. AB - This systematic review and meta-analysis summarizes the evidence on the prospective relationship between childhood sedentary behaviour and biomedical health indicators, overall and stratified by type of sedentary behaviour (TV viewing, computer use/games, screen time and objective sedentary time). PMID- 27552939 TI - [Authorisation procedures could be simpler]. AB - Increasing numbers of trials involving human subjects are being conducted at several centres simultaneously in the Netherlands. This multicentre research is, however, unnecessarily hampered by the major variation in procedures, processing times and costs of obtaining authorisation in each individual centre, even though it would not be difficult to streamline these essentially simple procedures and make them more transparent and cheaper. PMID- 27552940 TI - [Information is more than just the number]. AB - In order to be able to make informed choices, it is important that patients have transparent information about the pros and cons of treatment. When using the number unnecessarily treated (NUT) as information for patients, we should take the following into account. First, patients should understand that non-effective treatment may still do harm. This might be in contradiction with their ideas about the effects of treatment. Second, as many patients have difficulties understanding numbers and probabilities, the usefulness of NUT may be limited. Third, it is very important to use the proper presentation format to make the information intuitively meaningful for patients. A natural frequency tree and not a population diagram appears to be the optimal format for this purpose. When giving patient information the premise is that the form of the message is more important than the numbers. PMID- 27552942 TI - Hydrazones as Singular Reagents in Asymmetric Organocatalysis. AB - This Minireview summarizes strategies and developments regarding the use of hydrazones as reagents in asymmetric organocatalysis, their distinct roles in nucleophile-electrophile, cycloaddition, and cyclization reactions. The key structural elements governing the reactivity of these reagents in a preferred pathway will be discussed, as well as their different interactions with organocatalysts, leading to diverse activation modes. Along these studies, the synthetic equivalence of N-monoalkyl, N,N-dialkyl, and N-acyl hydrazones with several synthons is also highlighted. Emphasis is also put on the mechanistic studies performed to understand the observed reactivities. Finally, the functional group transformations performed from the available products has also been analyzed, highlighting the synthetic value of these methodologies, which served to access numerous families of valuable multifunctional compounds and nitrogen-containing heterocycles. PMID- 27552941 TI - Testosterone and sexual risk among transmen: a mixed methods exploratory study. AB - Little research has explored the link between the behavioural effects of testosterone use among transmen and HIV risk. We conducted a mixed methods study to explore testosterone use among transmen and the behavioural effects on HIV risk. A sample of 122 transmen from San Francisco participated in a cross sectional quantitative survey and 14 transmen participated in 2 focus group discussions. Most participants (81.9%) were currently taking hormones. Participants attributed testosterone use to new sexual behaviours among 69% of transmen, changes in sexual attraction (49%), and increased frequency of sexual activity (72%). Among current testosterone users, 3.3% had cisgender men as partners before starting testosterone, whereas after starting testosterone, 25.4% did. Similarly, 4.1% had a transgender woman as a sexual partner before starting testosterone and 13.9% after starting testosterone. Findings suggest that testosterone's side effects were associated with transmen's desires for sex with cisgender men who have sex with men. The reported increase in attraction to and sex with partners from populations with a high HIV prevalence may have important implications for HIV risk among transmen, especially as the availability of transgender health services may draw transmen to a context in which HIV prevalence is high. PMID- 27552943 TI - Neem cake as a promising larvicide and adulticide against the rural malaria vector Anopheles culicifacies (Diptera: Culicidae): a HPTLC fingerprinting approach. AB - Mosquitoes are insects of huge public health importance, since they act as vectors for important pathogens and parasites. Here, we focused on the possibility of using the neem cake in the fight against mosquito vectors. The neem cake chemical composition significantly changes among producers, as evidenced by our HPTLC (High performance thin layer chromatography) analyses of different marketed products. Neem cake extracts were tested to evaluate the ovicidal, larvicidal and adulticidal activity against the rural malaria vector Anopheles culicifacies. Ovicidal activity of both types of extracts was statistically significant, and 150 ppm completely inhibited egg hatching. LC50 values were extremely low against fourth instar larvae, ranging from 1.321 (NM1) to 1.818 ppm (NA2). Adulticidal activity was also high, with LC50 ranging from 3.015 (NM1) to 3.637 ppm (NM2). This study pointed out the utility of neem cake as a source of eco-friendly mosquitocides in Anopheline vector control programmes. PMID- 27552944 TI - Cancer vaccines in colon and rectal cancer over the last decade: lessons learned and future directions. AB - INTRODUCTION: Great advances have been made in screening for and treatment of colorectal cancer (CRC), but recurrence rates remain high and additional therapies are needed. There is great excitement around the field of immunotherapy and many attempts have been made to bring immunotherapy to CRC through a cancer vaccine. Areas covered: This is a detailed review of the last decade's significant CRC vaccine trials. Expert commentary: Monotherapy with a CRC vaccine is likely best suited for adjuvant therapy in disease free patients. Vaccine therapy elicits crucial tumor infiltrating lymphocytes, which are lacking in microsatellite-stable tumors, and therefore may be better suited for these patients. The combination of CRC vaccines with checkpoint inhibitors may unlock the potential of immunotherapy for a much broader range of patients. Future studies should focus on vaccine monotherapy in correctly selected patients and combination therapy in more advanced disease. PMID- 27552961 TI - Mesoporous TiO2 Nanocrystals/Graphene as an Efficient Sulfur Host Material for High-Performance Lithium-Sulfur Batteries. AB - Rechargeable lithium-sulfur (Li-S) batteries are promising in high-energy storage due to the large specific energy density of about 2600 W h kg(-1). However, the low conductivity of sulfur and discharge products as well as polysulfide-shuttle effect between the cathode and anode hamper applications of Li-S batteries. Herein, we describe a novel and efficient S host material consisting of mesoporous TiO2 nanocrystals (NCs) fabricated in situ on reduced graphene oxide (rGO) for Li-S batteries. The TiO2@rGO hybrid can be loaded with 72 wt % sulfur. The strong chemisorption ability of the TiO2 NCs toward polysulfide combined with high electrical conductivity of rGO effectively localize the soluble polysulfide species within the cathode and facilitate electron and Li ions transport to/from the cathode materials. The sulfur-incorporated TiO2@rGO hybrid (S/TiO2@rGO) shows large capacities of 1116 and 917 mA h g(-1) at the current densities of 0.2 and 1 C (1 C = 1675 mA g(-1)) after 100 cycles, respectively. When the current density is increased 20 times from 0.2 to 4 C, 60% capacity is retained, thereby demonstrating good cycling stability and rate capability. The synergistic effects of TiO2 NCs toward effective chemisorption of polysulfides and conductive rGO with high electron mobility make a promising application of S/TiO2@rGO hybrid in high-performance Li-S batteries. PMID- 27552962 TI - Prognostic indicators for mycosis fungoides in a Greek population. AB - BACKGROUND: Mycosis fungoides (MF) is an indolent cutaneous lymphoma with excellent prognosis at early stages and much poorer outcome during disease progression. Old age, male sex and folliculotropism have been proposed as relevant prognostic factors; however, their exact effect remains debatable. OBJECTIVES: To evaluate MF prognostic indicators and survival rates in a Greek population. METHODS: Prognostic variables affecting survival rates were studied in 473 patients with MF diagnosed and treated by two academic referral centres in Greece. Kaplan-Meier estimates were used to determine survival rates and progression. The Cox proportional hazards regression model was used to assess prognostic factors. RESULTS: The mean age of diagnosis was 61.7 years (SD 16.33). Five-year disease-specific survival was 96% in patients with stage IA disease and 52% in patients with stage IIB disease. Univariate analysis certified that large cell transformation, clonal rearrangements of the TCR gene, severe pruritus and presence of plaques were the most important prognostic factors. Folliculotropism altered disease progression only in patients with early-stage disease. The application of the Cutaneous Lymphoma International Prognostic Index (CLIPI) on our late-stage group failed to provide reliable evidence. The current Cutaneous Lymphoma International Consortium (CLIC) prognostic index can efficiently distinguish a low-risk from a high-risk group of patients. Tumour-Node-Metastasis Blood (TNMB) staging was the most important prognostic factor for survival rates in multivariate analysis. CONCLUSIONS: In our study we validated the current prognostic indicators for MF in a Greek population and identified new potential prognostic factors for survival outcome. Our findings contribute to the ongoing investigation of prognostic indicators of MF, further validation of which is highly needed through prospective studies and among different populations. PMID- 27552963 TI - Activation of the Carbon Nitride Surface by Silica in a CO-Evolving Hybrid Photocatalyst. AB - Photocatalytic reduction of CO2 to CO proceeded by visible light (lambda>400 nm) using mesoporous graphitic carbon nitride (C3 N4 ) coupled with a RuII -ReI binuclear complex (RuRe) containing a photosensitizer and catalytic units. The selectivity to CO exceeded 90 % during the initial stage. Photocatalytic reactions (including isotope tracer experiments) and electrochemical measurements revealed that the reaction proceeded according to a two-step photoexcitation of C3 N4 and the RuII photosensitizer unit, that is, it followed the Z-Scheme mechanism. Modification of C3 N4 with highly dispersed silica was found to improve the ability of C3 N4 to accommodate RuRe, which enhanced the photocatalytic activity for CO production. PMID- 27552964 TI - Chromosomal abnormalities in hepatic cysts point to novel polycystic liver disease genes. AB - Autosomal dominant polycystic liver disease (ADPLD) is caused by variants in PRKCSH, SEC63, and LRP5, whereas autosomal dominant polycystic kidney disease is caused by variants in PKD1 and PKD2. Liver cyst development in these disorders is explained by somatic loss-of-heterozygosity (LOH) of the wild-type allele in the developing cyst. We hypothesize that we can use this mechanism to identify novel disease genes that reside in LOH regions. In this study, we aim to map abnormal genomic regions using high-density SNP microarrays to find novel PLD genes. We collected 46 cysts from 23 patients with polycystic or sporadic hepatic cysts, and analyzed DNA from those cysts using high-resolution microarray (n=24) or Sanger sequencing (n=22). We here focused on regions of homozygosity on the autosomes (>3.0 Mb) and large CNVs (>1.0 Mb). We found frequent LOH in PRKCSH (22/29) and PKD1/PKD2 (2/3) cysts of patients with known heterozygous germline variants in the respective genes. In the total cohort, 12/23 patients harbored abnormalities outside of familiar areas. In individual ADPLD cases, we identified germline events: a 2q13 complex rearrangement resulting in BUB1 haploinsufficiency, a 47XXX karyotype, chromosome 9q copy-number loss, and LOH on chromosome 3p. The latter region was overlapping with an LOH region identified in two other cysts. Unique germline and somatic abnormalities occur frequently in and outside of known genes underlying cysts. Each liver cyst has a unique genetic makeup. LOH driver gene BUB1 may imply germline causes of genetic instability in PLD. PMID- 27552965 TI - Across-cohort QC analyses of GWAS summary statistics from complex traits. AB - Genome-wide association studies (GWASs) have been successful in discovering SNP trait associations for many quantitative traits and common diseases. Typically, the effect sizes of SNP alleles are very small and this requires large genome wide association meta-analyses (GWAMAs) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study, we propose four metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We propose methods to examine the concordance between demographic information, and summary statistics and methods to investigate sample overlap. (I) We use the population genetics Fst statistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. (II) We conduct principal component analysis based on reported allele frequencies, and are able to recover the ancestral information for each cohort. (III) We propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. (IV) To quantify unknown sample overlap across all pairs of cohorts, we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy. PMID- 27552966 TI - Who should have access to genomic data and how should they be held accountable? Perspectives of Data Access Committee members and experts. AB - Facilitating the responsible access to genomic research data is an emerging ethical and scientific imperative. Data Access Committees (DACs) assess the ethical footing and scientific feasibility of the data access requests and evaluate the qualification of applicants to ensure they are bona fide researchers. Through semi-structured interviews, we explored the opinions and experiences of 20 DAC members and experts concerning the users' qualification criteria and mechanisms to hold users accountable. According to our respondents, such evaluation is necessary to ensure applicants are trustworthy, meet a certain level of expertise or experience and are aware of the rules and the associated concerns with genomic data sharing. The respondents noted, however, that the qualification criteria are fragmented or are poorly delineated at times. Thus, developing qualification criteria seems vital for an objective, fair and responsible access procedure. Similarly, the access review will benefit from using common ways of verifying the users' affiliations. Furthermore, some DAC members expressed concern over the uncertain oversight of downstream data use, in particular where data are shared across borders. DAC members and experts did not consider current sanctions and enforcement procedures to be crystal clear. Therefore, data sharing policies should address this gap by establishing proportionate sanctions both against data producers and data users' non compliance. Users' home institutes will need to have an active role in keeping oversight on the downstream data uses, considering their ultimate responsibility if wrongdoings happen. PMID- 27552967 TI - Bis(difluoromethyl)trimethylsilicate Anion: A Key Intermediate in Nucleophilic Difluoromethylation of Enolizable Ketones with Me3 SiCF2 H. AB - A pentacoordinate bis(difluoromethyl)silicate anion, [Me3 Si(CF2 H)2 ](-) , is observed for the first time by the activation of Me3 SiCF2 H with a nucleophilic alkali-metal salt and 18-crown-6. Further study on its reactivity by tuning the countercation effect led to the discovery and development of an efficient, catalytic nucleophilic difluoromethylation of enolizable ketones with Me3 SiCF2 H by using a combination of CsF and 18-crown-6 as the initiation system. Mechanistic investigations demonstrate that [(18-crown-6)Cs](+) [Me3 Si(CF2 H)2 ](-) is a key intermediate in this catalytic reaction. PMID- 27552968 TI - Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer. AB - BACKGROUND: Colorectal cancer (CRC) is 3rd most commonly diagnosed cancer in males and the second in females. PD-1/PD-L1 axis, as an immune checkpoint, is up regulated in many tumors and their microenvironment. However, the prognostic value of PD-1/PD-L1 in CRC remains unclear. METHODS: The Cancer Genome Atlas (TCGA) database (N = 356) and Fudan University Shanghai Cancer Center (FUSCC) cohort of patients (N = 276) were adopted to analyze the prognostic value of PD L1 in colorectal tumor cells (TCs) and of PD-1 in tumor infiltrating cells (TILs) for CRC. Subgroup analyses were conducted in FUSCC cohort according to patients' status of mismatch repair. RESULTS: In TCGA cohort, the cut-off values of PD-1 and PD-L1 expression were determined by X-tile program, which were 4.40 and 2.92, respectively. Kaplan-Meier analysis indicated that higher PD-1 and PD-L1 expressions correlated with better OS (P = 0.032 and P = 0.002, respectively). In FUSCC cohort, expressions of PD-1 on TILs and PD-L1 on TCs were analyzed separately by immunohistochemistry (IHC) staining based on a TMA sample (N = 276) and revealed that both TILs-PD-1 and TCs-PD-L1 were associated with OS (P = 0.006 and P = 0.002, respectively) and DFS (P = 0.025 and P = 0.004, respectively) of CRC patients. Multivariate Cox regression analysis indicated TILs-PD-1 was an independent prognostic factor both for OS and DFS of CRC patients (P < 0.05). Subgroup analyses showed that TILs-PD-1 was an independent prognostic factor for both OS and DFS in CRC patients in MSS-proficient subgroup (P < 0.05), while neither of them correlated with OS or DFS in MSS-deficient subgroup (P > 0.05). CONCLUSIONS: Higher expressions of PD-1 and PD-L1 correlates with better prognosis of CRC patients. TILs-PD-1 is an independent prognostic factor for OS and DFS of CRC patients, especially for MMR-proficient subgroup. PMID- 27552969 TI - Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. AB - The capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O(6)-methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n=52), grade (n=128) and ALT activation (n=46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time. PMID- 27552972 TI - Post-translational modifications: Extension of the tubulin code. PMID- 27552970 TI - Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review. AB - Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer. PMID- 27552973 TI - Coenzyme A: to make it or uptake it? AB - The consensus has been that intracellular coenzyme A (CoA) is obtained exclusively by de novo biosynthesis via a universal, conserved five-step pathway in the cell cytosol. However, old and new evidence suggest that cells (and some microorganisms) have several strategies to obtain CoA, with 4'-phosphopantetheine (P-PantSH; the fourth intermediate in the canonical CoA biosynthetic pathway) serving as a 'nexus' metabolite. PMID- 27552971 TI - Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. AB - The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD+) dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD+ precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others. These advances have demonstrated that it is possible to rationally design molecules that can alleviate multiple diseases and possibly extend lifespan in humans. PMID- 27552975 TI - Comparative lever analysis and ontogenetic scaling in esocid fishes: Functional demands and constraints in feeding biomechanics. AB - When animals grow, the functional demands that they experience often change as a consequence of their increasing body size. In this study, we examined the feeding biomechanics in esocid species that represent different size classes (small, Esox americanus; intermediate, Esox niger; large, Esox lucius), and how their bite forces and associated functional variables change as they grow. In order to evaluate bite performance through ontogeny, we dissected and measured dimensions of the feeding apparatus and the adductor mandibulae muscle complex with its segmentum facialis subdivisions such as the ricto-malaris, stegalis and endoricto malaris across a wide range of body sizes. The collected morphological data was used as input variables for a published anatomical model to simulate jaw function in these fish species. Maximum bite forces for both anterior bite and posterior bite increased in isometry in E. americanus and E. niger. The posterior bite of E. lucius also increases in isometry, however, the anterior bite increases in positive allometry. Intraspecific comparison within E. lucius indicated the increase of bite forces in more developed individuals accelerated after the fish grew out of fingerling stage. In addition, our analysis indicated functional differentiation between subdivisions of the adductor mandibulae segmentum facialis, as well as interspecific differences in the pattern of contribution to the bite performance by these subdivisions. Our study provides insights into not only the musculoskeletal basis of the jaw function of esocid species, but also the feeding capacity of this species in relation to the functional demands it faces as one of the top predators in lake and river systems. J. Morphol. 277:1447 1458, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27552974 TI - Control of brown and beige fat development. AB - Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli - notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells, and have revealed unanticipated cell-lineage relationships between vascular smooth muscle cells and beige adipocytes, and between skeletal muscle cells and brown fat. In addition, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells, have crucial roles in regulating the differentiation and function of brown and beige fat. PMID- 27552976 TI - Evaluation of pregnancy outcomes from the Tysabri(r) (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. AB - BACKGROUND: Patients with multiple sclerosis (MS) or Crohn's disease (CD) being treated with natalizumab (Tysabri(r), Biogen) who are planning to become pregnant or discover they are pregnant after exposure to natalizumab are currently advised to balance the potential benefits and potential risks of exposure when considering treatment options. This study was undertaken to evaluate pregnancy outcomes of women with MS or CD who were exposed to natalizumab at any time within 3 months prior to conception or during pregnancy. A pregnancy registry was created to better understand the effect of natalizumab exposure on pregnancy outcomes. METHODS: The Tysabri Pregnancy Exposure Registry was a global, observational exposure registration and follow-up study. Evaluations included spontaneous abortions (<22 weeks gestational age), fetal losses (>=22 weeks gestational age), ectopic pregnancies, elective or therapeutic terminations, stillbirths, birth defects, and live births. Birth defects were reviewed and coded in accordance with the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of birth defects. RESULTS: A total of 369 patients with MS and 7 patients with CD were enrolled prospectively, of whom 355 patients (99.4 %; 349 MS and 6 CD) had known pregnancy outcomes (including 8 twin sets). The spontaneous abortion rate was 9.0 % (n = 32; 95 % confidence interval [C. I.], 6.3-12.5 %). An independent advisory committee review determined the major birth defect rate to be 5.05 % (16 of 316 live births + 1 elective abortion; 95 % C. I., 2.9-8.1 %). The mean gestational age of the live-born infants was 38.3 weeks, and the mean birth weight was 3158.3 g. CONCLUSIONS: Although the overall rate of birth defects was higher than that observed by the MACDP, these registry outcomes showed no specific pattern of malformations that would suggest a drug effect, and the spontaneous abortion rate was consistent with that of the general population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00472992 (11 May 2007). PMID- 27552977 TI - Development of a self-assessment teamwork tool for use by medical and nursing students. AB - BACKGROUND: Teamwork training is an essential component of health professional student education. A valid and reliable teamwork self-assessment tool could assist students to identify desirable teamwork behaviours with the potential to promote learning about effective teamwork. The aim of this study was to develop and evaluate a self-assessment teamwork tool for health professional students for use in the context of emergency response to a mass casualty. METHODS: The authors modified a previously published teamwork instrument designed for experienced critical care teams for use with medical and nursing students involved in mass casualty simulations. The 17-item questionnaire was administered to students immediately following the simulations. These scores were used to explore the psychometric properties of the tool, using Exploratory and Confirmatory Factor Analysis. RESULTS: 202 (128 medical and 74 nursing) students completed the self assessment teamwork tool for students. Exploratory factor analysis revealed 2 factors (5 items - Teamwork coordination and communication; 4 items - Information sharing and support) and these were justified with confirmatory factor analysis. Internal consistency was 0.823 for Teamwork coordination and communication, and 0.812 for Information sharing and support. CONCLUSIONS: These data provide evidence to support the validity and reliability of the self-assessment teamwork tool for students This self-assessment tool could be of value to health professional students following team training activities to help them identify the attributes of effective teamwork. PMID- 27552978 TI - Prevalence of CT features of axial spondyloarthritis in patients with Crohn's disease. AB - Background The sacroiliac joint and spine are seen on abdominal computed tomography (CT) and may show structural lesions as part of spondyloarthritis. Purpose To determine the prevalence of CT features of spondyloarthritis in patients with Crohn's disease (CD). Material and Methods A retrospective study of structural lesions of spondyloarthritis on abdominal CT was performed. The sacroiliac joints and spine of 120 patients were studied: study group I consisted of 40 patients with known CD and inflammatory back pain, group II involved 40 patients with CD without inflammatory back pain, and group III consisted of 40 patients without known joint or inflammatory bowel disease. Recorded CT features included sclerosis, erosions or ankylosis of the sacroiliac joint, enthesopathy, spinal syndesmophytes, and costovertebral joint lesions. Results CT showed structural lesions of the sacroiliac joints in 19/40 (48%) patients with CD and inflammatory back pain (sclerosis [n = 14; 35%], erosions [n = 14; 35%], ankylosis [n = 3; 8%]), in 8/40 (8%) patients with CD without inflammatory back pain (sclerosis [n = 3; 8%], erosions [n = 4; 10%], ankylosis [n = 3; 8%]), and in 3/40 (8%) patients without known joint or bowel disease (sclerosis [n = 2; 5%], ankylosis [n = 1; 3%]). Syndesmophytes were exclusively seen in group I (n = 6; 15%). Conclusion CT of the abdomen in patients with CD and inflammatory back pain shows structural lesions of the sacroiliac joint, entheses, or spine in almost half of the patients. Awareness and knowledge of these findings may guide the referring clinician to further clinical evaluation, imaging, and biomarker evaluation of the disease. PMID- 27552979 TI - MR imaging of the anatomy of the anterior horn of the medial meniscus. AB - Background In cadaveric and arthroscopic studies different insertion locations of the anterior horn of the medial meniscus (AHMM) have been described. Purpose To investigate if the different insertion locations of the AHMM, as described in cadaveric studies, can be determined on magnetic resonance imaging (MRI). Material and Methods MR images of 100 patients without meniscal tears on MRI were retrospectively evaluated. Two observers classified the AHMM insertion based on its position relative to the anterior tibial edge and the medial tibial spine. The association between AHMM insertion and tibial plateau slope, meniscal radial displacement, and anterior intermeniscal ligament (AIL) presence was investigated. Results The AHMM inserted posterior to the anterior tibial edge in 93 knees and anterior to the tibial edge in seven knees (= type III). Of the 93 knees with AHMM insertion posterior to the anterior tibial edge, 63 inserted lateral to the medial tibial spine (= type I) and 30 medial (= type II). The AHMMs inserting anterior to the tibial edge had a significantly ( P < 0.05) steeper anterior tibial plateau slope and a significantly ( P < 0.05) higher presence of the AIL. No significant difference in radial displacement was observed between the three insertion types ( P > 0.05). A strong inter- and intra observer agreement was observed. Conclusion Three different bony insertion locations of the AHMM, as described in cadaveric studies, could be identified on MRI. All AHMMs inserting anterior to the tibial edge displayed an AIL. Whether there is a clinical correlation with these insertion patterns remains unclear. PMID- 27552980 TI - C-arm cone-beam computed tomography with stereotactic needle guidance for percutaneous adrenal biopsy: initial experience. AB - Background Metastasis to the adrenal glands is frequent in patients with various cancers and adrenal gland biopsy is routinely performed using ultrasound or computed tomographic (CT) guidance. However, this method is technically challenging, especially in the case of small masses. Purpose To determine whether the new real-time stereotactic needle guidance technique C-arm cone-beam CT (CBCT) allows safe and accurate biopsy of adrenal gland masses, especially those in hard-to-reach anatomical locations. Material and Methods CBCT guidance was used to perform 60 stereotactic biopsy procedures of lesions that were inaccessible with ultrasound or CT guidance. The needle path was carefully planned and calculated on the CBCT virtual navigation guidance system, which acquired 3D CT-like cross-sectional images. The adrenal biopsy procedures were performed with fluoroscopic feedback. Technical success rate, sensitivity, specificity, accuracy, and complications were investigated. Results The technical success rate of adrenal biopsy under CBCT virtual navigation was 100%, with a mean total procedure time of 14.6 +/- 3.6 min. Of the 60 lesions, 46 were malignant, 11 were benign, and three were non-diagnostic. The three non diagnostic lesions proved to be malignant. Thus, the sensitivity, specificity, and accuracy were 93.8%, 100%, and 95.0%, respectively. Minor bleeding occurred in two (3.3%) cases. Conclusion CBCT guidance allows safe and accurate biopsy of adrenal gland masses and may be especially useful for hard-to-reach anatomical locations. PMID- 27552981 TI - Triple rule-out CT angiography protocol with restricting field of view for detection of pulmonary thromboembolism and aortic dissection in emergency department patients: simulation of modified CT protocol for reducing radiation dose. AB - Background Triple rule-out computed tomography (TRO CT) is a CT protocol designed to simultaneously evaluate the coronary, aorta, and pulmonary arteries. Purpose To evaluate potential diagnostic performance of TRO CT with restricted volume coverage for detection of pulmonary thromboembolism (PTE) and aortic dissection (AD). Material and Methods This study included 1224 consecutive patients with acute chest pain who visited the emergency department and underwent TRO CT using a 128-slice dual-source CT. Image data were reconstructed according to the display field of view (DFOV) of coronary CT angiography (CCTA) and TRO CT protocols in each patient. The presence of PTE and AD was evaluated by independent observers in each DFOV. The radiation dose was calculated to evaluate the potential benefits by restricting z-axis coverage to cardiac scan range instead of the whole thorax. Results Among all patients, 22 cases with PTE (1.9%) and nine cases with AD (0.8%) were found. Except for one PTE case, all cases were detected on both DFOV of TRO CT and CCTA. Mean effective dose for evaluation of entire thorax and cardiac scan coverage were 5.9 +/- 1.1 mSv and 3.5 +/- 0.7 mSv, respectively. Conclusion Isolated PTE and AD outside the CCTA DFOV rarely occur. Therefore, modified TRO CT protocol using cardiac scan coverage can be adopted to detect PTE and AD with reduced radiation dose. PMID- 27552982 TI - Health Threats from Contamination of Spices Commercialized in Romania: Risks of Fungal and Bacterial Infections. AB - BACKGROUND: The study of fungal contamination in food and mycotoxicoses is a priority today, both internationally and nationally. The purpose of this study is to have a general view over the quality of the most common spices that are sold in Romanian markets, by assessing the degree of fungal, bacterial and mycotoxin contamination in pepper and chili powders. METHODS: We tested four types of spices: white pepper, black pepper, sweet and hot chili powders from 12 different distributing companies, summing a total of 35 sample types. The fungal and bacterial load was assessed by Standard Plate Count, while the mycotoxin content by High-performance liquid chromatography. Environmental conditions (humidity, pH) and the selling price for each product were also followed. RESULTS: Fungi were observed in 72.7% of black pepper samples, 33.3% in white pepper, 30% in sweet chili and 25% in hot chili products. The most common isolated fungus was Aspergillus spp., while Rhizopus, Mucor, Fusarium, Penicillium, Absidia species were found, in smaller percentage. Four producers (44.4%) presented fungal contamination of over 10^3 CFU/g and two producers (22.2%) presented no fungal contamination in their products. Bacterial contamination was found in 85.7% of the tested products, consisting mostly in Bacillus spp. Aflatoxin B1 was present in all the tested products, mostly in black pepper (mean value 126.3 ng/g); Ochratoxin A was present in sweet chili (mean value 328 ng/g) and Zearalenone in hot chili (mean value 604 ng/g) and sweet chili (mean value 382 ng/g). CONCLUSION: All spices presented either fungal contamination, mycotoxin contamination, or both. The high humidity and the high pH of spices represent favorable conditions for fungal growth. The selling price was partly related to the physic-chemical conditions and microbiological quality of the spices. PMID- 27552983 TI - Understanding the failure of a behavior change intervention to reduce risk behaviors for avian influenza transmission among backyard poultry raisers in rural Bangladesh: a focused ethnography. AB - BACKGROUND: The spread of the highly pathogenic avian influenza (HPAI) H5N1 virus among poultry and humans has raised global concerns and has motivated government and public health organizations to initiate interventions to prevent the transmission of HPAI. In Bangladesh, H5N1 became endemic in poultry and seven human H5N1 cases have been reported since 2007, including one fatality. This study piloted messages to increase awareness about avian influenza and its prevention in two rural communities, and explored change in villagers' awareness and behaviors attributable to the intervention. METHODS: During 2009-10, a research team implemented the study in two rural villages in two districts of Bangladesh. The team used a focused ethnographic approach for data collection, including informal interviews and observations to provide detailed contextual information about community response to a newly emerging disease. They collected pre-intervention qualitative data for one month. Then another team disseminated preventive messages focused on safe slaughtering methods, through courtyard meetings and affixed posters in every household. After dissemination, the research team collected post-intervention data for one month. RESULTS: More villagers reported hearing about 'bird flu' after the intervention compared to before the intervention. After the intervention, villagers commonly recalled changes in the color of combs and shanks of poultry as signs of avian influenza, and perceived zoonotic transmission of avian influenza through direct contact and through inhalation. Consequently the villagers valued covering the nose and mouth while handling sick and dead poultry as a preventive measure. Nevertheless, the team did not observe noticeable change in villagers' behavior after the intervention. Villagers reported not following the recommended behaviors because of the perceived absence of avian influenza in their flocks, low risk of avian influenza, cost, inconvenience, personal discomfort, fear of being rebuked or ridiculed, and doubt about the necessity of the intervention. CONCLUSIONS: The villagers' awareness about avian influenza improved after the intervention, however, the intervention did not result in any measurable improvement in preventive behaviors. Low cost approaches that promote financial benefits and minimize personal discomfort should be developed and piloted. PMID- 27552985 TI - Gene name errors are widespread in the scientific literature. AB - The spreadsheet software Microsoft Excel, when used with default settings, is known to convert gene names to dates and floating-point numbers. A programmatic scan of leading genomics journals reveals that approximately one-fifth of papers with supplementary Excel gene lists contain erroneous gene name conversions. PMID- 27552984 TI - Transcriptomic analysis of differentially expressed genes in the floral transition of the summer flowering chrysanthemum. AB - BACKGROUND: Chrysanthemum is a leading cut flower species. Most conventional cultivars flower during the fall, but the Chrysanthemum morifolium 'Yuuka' flowers during the summer, thereby filling a gap in the market. To date, investigations of flowering time determination have largely focused on fall flowering types. Little is known about molecular basis of flowering time in the summer-flowering chrysanthemum. Here, the genome-wide transcriptome of 'Yuuka' was acquired using RNA-Seq technology, with a view to shedding light on the molecular basis of the shift to reproductive growth as induced by variation in the photoperiod. RESULTS: Two sequencing libraries were prepared from the apical meristem and leaves of plants exposed to short days, three from plants exposed to long days and one from plants sampled before any photoperiod treatment was imposed. From the ~316 million clean reads obtained, 115,300 Unigenes were assembled. In total 70,860 annotated sequences were identified by reference to various databases. A number of transcription factors and genes involved in flowering pathways were found to be differentially transcribed. Under short days, genes acting in the photoperiod and gibberellin pathways might accelerate flowering, while under long days, the trehalose-6-phosphate and sugar signaling pathways might be promoted, while the phytochrome B pathway might block flowering. The differential transcription of eight of the differentially transcribed genes was successfully validated using quantitative real time PCR. CONCLUSIONS: A transcriptome analysis of the summer-flowering cultivar 'Yuuka' has been described, along with a global analysis of floral transition under various daylengths. The large number of differentially transcribed genes identified confirmed the complexity of the regulatory machinery underlying floral transition. PMID- 27552986 TI - Incidence of immediate postpartum hemorrhages in French maternity units: a prospective observational study (HERA study). AB - BACKGROUND: Most estimates of postpartum hemorrhage (PPH) are calculated from studies that use administrative or medical birth databases, and only a few from prospective observational studies. Our principal objective was to estimate the incidence of PPH according to their severity (mild or severe) in vaginal deliveries (>500 mL, >=1000 mL) and cesareans (>1000 mL and >=1500 mL). The secondary objectives were to describe the incidence of PPH according to maternity unit characteristics, causes, and types of PPH management. METHODS: This prospective observational study took place in French maternity wards. Women who gave birth at a term >= 22 weeks were eligible for the study. 182 maternity units participated in a study with prospective data collection from 1 February, 2011, to 31 July, 2011. The main outcome measure was PPH incidence. RESULTS: PPH incidence after vaginal delivery was 3.36 % [95 % CI: 3.25-3.47 %] and after cesareans 2.83 % [95 % CI: 2.63-3.04 %]. The incidence of severe PPH after vaginal delivery was 1.11 % [95 % CI: 1.05-1.18 %] and after cesareans 1.00 % [95 % CI: 0.88-1.13 %]. This incidence rate varied according to maternity unit characteristics. The principal cause of PPH for both modes of delivery was uterine atony (57.7 % for vaginal births and 66.3 % for cesareans). Vascular embolization was more frequent among women with cesareans (10.0 vs. 2.9 %), who also required transfusions more often (44.4 vs 12.7 %). CONCLUSIONS: The incidence of PPH was lower than the rate expected from the literature. Effective treatment of uterine atony and optimizing the identification of blood loss remain important priorities. PMID- 27552987 TI - Improving management of student clinical placements: insights from activity theory. AB - BACKGROUND: An approach to improve management of student clinical placements, the Building Teams for Quality Learning project, was trialed in three different health services. In a previous paper the authors explored in some detail the factors associated with considerable success of this approach at one of these services. In this paper, the authors extend this work with further analysis to determine if the more limited outcomes observed with participants at the other two services could be explained by application of activity theory and in particular the expansive learning cycle. METHODS: Staff at three health services participated in the Building Teams for Quality Learning project: a dental clinic, a community aged care facility and a rural hospital. At each site a team of seven multi-disciplinary staff completed the project over 9 to 12 months (total 21 participants). Evaluation data were collected through interviews, focus groups and direct observation of staff and students. Following initial thematic analysis, further analysis was conducted to compare the processes and outcomes at each participating health service drawing on activity theory and the expansive learning cycle. RESULTS: Fifty-one interview transcripts, 33 h of workplace observation and 31 sets of workshop field notes (from 36 h of workshops) were generated. All participants were individually supportive of, and committed to, high quality student learning experiences. As was observed with staff at the dental clinic, a number of potentially effective strategies were discussed at the aged care facility and the rural hospital workshops. However, participants in these two health services could not develop a successful implementation plan. The expansive learning cycle element of modeling and testing new solutions was not achieved and participants were unable, collectively to reassess and reinterpret the object of their activities. CONCLUSION: The application of activity theory and the expansive learning cycle assisted a deeper understanding of the differences in outcomes observed across the three groups of participants. This included identifying specific points in the expansive learning cycle at which the three groups diverged. These findings support some practical recommendations for health services that host student clinical placements. PMID- 27552988 TI - Prognostic value of new left atrial volume index severity partition cutoffs after cardiac rehabilitation program in patients undergoing cardiac surgery. AB - BACKGROUND: Previous studies showed that left atrial enlargement is an independent marker of adverse outcomes in both primary and secondary cardiovascular prevention. However, no data are available on long-term outcomes in patients undergoing valve surgery and/or coronary artery by-pass graft (CABG) surgery. Aim of the study was to evaluate long-term prognostic role of left atrial volume index (LAVi) after cardiac surgery, using the cutoff values recently proposed by the European Association of Cardiovascular Imaging and American Society of Echocardiography. METHODS: We created a retrospective registry of 1703 consecutive patients who underwent cardiovascular rehabilitation program after cardiac surgery, including CABG, valve surgery and valve + CABG surgery. LAVi was calculated as ratio of left atrium volume to body surface area, in ml/m(2) at discharge; 563 patients with available LAVi data were included in the study. RESULTS: In the whole population LAVi was 36 +/- 14 ml/m(2) (mean +/- SD) and the follow-up time was 5 +/- 1.5 years. Increased LAVi (>34 ml/m(2)) predicted major adverse cardiovascular and cerebrovascular events (MACCEs) (HR = 2.1; CI95 %: 1.4-3.1; p < 0.001) and cardiovascular mortality (HR = 2.2; CI95 %: 1.0-4.5; p = 0.032). An increased LAVi remained MACCEs predictor after adjustement for age, gender, diabetes, atrial fibrillation at discharge, echocardiographic E/A ratio and left ventricular ejection fraction (HR = 1.8; CI95 %: 1.0-3.0; p = 0.036). When the study population was split according to increasing LAVi values, left atrium enlargement resulted a predictor of progressively worse adverse outcome. CONCLUSIONS: LAVi is a predictor of long term adverse cardiovascular outcome after cardiac surgery, even after correction for main clinical and echocardiographic variables. The recently recommended LAVi severity cutoffs appear adequate to effectively stratify outcome in patients undergoing rehabilitation after cardiac surgery. PMID- 27552989 TI - Missing gene identification using functional coherence scores. AB - Reconstructing metabolic and signaling pathways is an effective way of interpreting a genome sequence. A challenge in a pathway reconstruction is that often genes in a pathway cannot be easily found, reflecting current imperfect information of the target organism. In this work, we developed a new method for finding missing genes, which integrates multiple features, including gene expression, phylogenetic profile, and function association scores. Particularly, for considering function association between candidate genes and neighboring proteins to the target missing gene in the network, we used Co-occurrence Association Score (CAS) and PubMed Association Score (PAS), which are designed for capturing functional coherence of proteins. We showed that adding CAS and PAS substantially improve the accuracy of identifying missing genes in the yeast enzyme-enzyme network compared to the cases when only the conventional features, gene expression, phylogenetic profile, were used. Finally, it was also demonstrated that the accuracy improves by considering indirect neighbors to the target enzyme position in the network using a proper network-topology-based weighting scheme. PMID- 27552990 TI - Endovenous laser ablation versus mechanochemical ablation with ClariVein((r)) in the management of superficial venous insufficiency (LAMA trial): study protocol for a randomised controlled trial. AB - BACKGROUND: Endovenous thermal techniques, such as endovenous laser ablation (EVLA), are the recommended treatment for truncal varicose veins. However, a disadvantage of thermal techniques is that it requires the administration of tumescent anaesthesia, which can be uncomfortable. Non-thermal, non-tumescent techniques, such as mechanochemical ablation (MOCA) have potential benefits. MOCA combines physical damage to endothelium using a rotating wire, with the infusion of a liquid sclerosant. Preliminary experiences with MOCA showed good results and less post-procedural pain. METHODS/DESIGN: The Laser Ablation versus Mechanochemical Ablation (LAMA) trial is a single-centre randomised controlled trial in which 140 patients will be randomly allocated to EVLA or MOCA. All patients with primary truncal superficial venous insufficiency (SVI) who meet the eligibility criteria will be invited to participate in this trial. The primary outcomes are intra-procedural pain and technical efficacy at 1 year, defined as complete occlusion of target vein segment and assessed using duplex ultrasound. Secondary outcomes are post-procedural pain, analgesia use, procedure time, clinical severity, generic and disease-specific quality of life, bruising, complications, satisfaction, cosmesis, time taken to return to daily activities and/or work, and cost-effectiveness analysis following EVLA or MOCA. Both groups will be evaluated on an intention-to-treat basis. DISCUSSION: The aim of the LAMA trial is to establish whether MOCA is superior to the current first-line treatment, EVLA. The two main hypotheses are that MOCA may cause less initial pain and disability allowing a more acceptable treatment with an enhanced recovery. The second hypothesis is that this may come at a cost of decreased efficacy, which may lead to increased recurrence and affect longer term quality of life, increasing the requirement for secondary procedures. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02627846 , registered 8 December 2015 EudraCT number: 2015-000730-30 REC ref: 15/YH/0207 R&D ref: R1788. PMID- 27552991 TI - Myelodysplasia-associated mutations in serine/arginine-rich splicing factor SRSF2 lead to alternative splicing of CDC25C. AB - BACKGROUND: Serine-arginine rich splicing factor 2 (SRSF2) is a protein known for its role in RNA splicing and genome stability. It has been recently discovered that SRSF2, along with other splicing regulators, is frequently mutated in patients with myelodysplastic syndrome (MDS). The most common MDS mutations in SRSF2 occur at proline 95; the mutant proteins are shown to have different RNA binding preferences, which may contribute to splicing changes detected in mutant cells. However, the influence of these SRSF2 MDS-associated mutations on specific splicing events remains poorly understood. RESULTS: A tetracycline-inducible TF-1 erythroleukemia cell line was transduced with retroviruses to create cell lines expressing HA-tagged wildtype SRSF2, SRSF2 with proline 95 point mutations found in MDS, or SRSF2 with a deletion of one of the four major domains of the protein. Effects of these mutants on apoptosis and specific alternative splicing events were evaluated. Cells were also treated with DNA damaging drugs for comparison. MDS-related P95 point mutants of SRSF2 were expressed and phosphorylated at similar levels as wildtype SRSF2. However, cells expressing mutant SRSF2 exhibited higher levels of apoptosis than cells expressing wildtype SRSF2. Regarding alternative splicing events, in nearly all examined cases, SRSF2 P95 mutants acted in a similar fashion as the wildtype SRSF2. However, cells expressing SRSF2 P95 mutants had a percent increase in the C5 spliced isoform of cell division cycle 25C (CDC25C). The same alternative splicing of CDC25C was detected by treating cells with DNA damaging drugs, such as cisplatin, camptothecin, and trichostatin A at appropriate dosage. However, unlike DNA damaging drugs, SRSF2 P95 mutants did not activate the Ataxia telangiectasia mutated (ATM) pathway. CONCLUSION: SRSF2 P95 mutants lead to alternative splicing of CDC25C in a manner that is not dependent on the DNA damage response. PMID- 27552992 TI - The risk of pulmonary tuberculosis in underground copper miners in Zambia exposed to respirable silica: a cross-sectional study. AB - BACKGROUND: Pulmonary tuberculosis (PTB) among underground miners exposed to silica remains a global problem. Although well described in gold and coal mining, risk in other mining entities are not as well documented. This study aims to determine dust-related dose response risk for PTB among underground miners exposed to silica dust in Zambia's copper mines. METHODS: A cross sectional study of in-service miners (n = 357) was conducted at Occupational Health and Safety Institute (OHSI), Zambia. A systematic review of medical data over a 5-year period from assessments conducted by doctors at OHSI and statutory silica exposure data (n = 16678) from the Mine Safety Department (MSD) were analysed. Lifetime cumulative exposure metrics were calculated. Multivariate logistic regression analysis was used to determine the association between PTB and lifetime exposure to silica, while adjusting for various confounders. RESULTS: The median respirable silica dust level was 0.3 mg/m(3) (range 0.1-1.3). The overall prevalence of PTB was 9.5 % (n = 34). High cumulative respirable silica dust category showed a statistically significant association with PTB (OR = 6.4 (95 % CI 1. 8-23)) and a significant trend of increasing disease prevalence with increasing cumulative respirable silica dust categories was observed (ptrend < 0.01). Smoking showed a statistically significant association with PTB with OR = 4.3 (95 % CI 1.9-9.9). CONCLUSIONS: Our results demonstrate the association of increased risk for certified active TB with cumulative respirable dust in a dose related manner among this sample of copper miners. There is need to intensify dust control measures and incorporate anti-smoking interventions into TB prevention and control programmes in the mines. PMID- 27552993 TI - Pre-surgical depression and anxiety and recovery following coronary artery bypass graft surgery. AB - We aimed to explore the combined contribution of pre-surgical depression and anxiety symptoms for recovery following coronary artery bypass graft (CABG) using data from 251 participants. Participants were assessed prior to surgery for depression and anxiety symptoms and followed up at 12 months to assess pain and physical symptoms, while hospital emergency admissions and death/major adverse cardiac events (MACE) were monitored on average 2.68 years after CABG. After controlling for covariates, baseline anxiety symptoms, but not depression, were associated with greater pain (beta = 0.231, p = 0.014) and greater physical symptoms (beta = 0.194, p = 0.034) 12 months after surgery. On the other hand, after controlling for covariates, baseline depression symptoms, but not anxiety, were associated with greater odds of having an emergency admission (OR 1.088, CI 1.010-1.171, p = 0.027) and greater hazard of death/MACE (HR 1.137, CI 1.042 1.240, p = 0.004). These findings point to different pathways linking mood symptoms with recovery after CABG surgery. PMID- 27552994 TI - Accumulation of Cr, Cd, Pb, Cu, and Zn by plants in tanning sludge storage sites: opportunities for contamination bioindication and phytoremediation. AB - Tanning sludge enriched with high concentrations of Cr and other metals has adverse effects on the environment. Plants growing in the metalliferous soils may have the ability to cope with high metal concentrations. This study focuses on potentials of using native plants for bioindication and/or phytoremediation of Cr contaminated sites. In the study, we characterized plants and soils from six tanning sludge storage sites. Soil in these sites exhibited toxic levels of Cr (averaged 16,492 mg kg-1) and other metals (e.g., 48.3 mg Cu kg-1, 2370 mg Zn kg 1, 44.9 mg Pb kg-1, and 0.59 mg Cd kg-1). Different metal tolerance and accumulation patterns were observed among the sampled plant species. Phragmites australis, Zephyranthes candida, Cynodon dactylon, and Alternanthera philoxeroides accumulated moderate-high concentrations of Cr and other metals, which could make them good bioindicators of heavy metal pollution. High Cr and other metal concentrations (e.g., Cd and Pb) were found in Chenopodium rubrum (372 mg Cr kg-1), Aster subulatus (310 mg Cr kg-1), and Brassica chinensis (300 mg Cr kg-1), being considered as metal accumulators. In addition, Nerium indicum and Z. candida were able to tolerate high concentrations of Cr and other metals, and they may be used as preferable pioneer species to grow or use for restoration in Cr-contaminated sites. This study can be useful for establishing guidelines to select the most suitable plant species to revegetate and remediate metals in tanning sludge-contaminated fields. PMID- 27552995 TI - Response of sediment calcium and magnesium species to the regional acid deposition in eutrophic Taihu Lake, China. AB - Acid deposition causes carbonate dissolution in watersheds and leads to profound impacts on water chemistry of lakes. Here, we presented a detailed study on the seasonal, spatial, and vertical variations of calcium and magnesium species in the overlying water, interstitial water, and sediment profiles in eutrophic Taihu Lake under the circumstance of regional acid deposition. The result showed that both the acid deposition and biomineralization in Taihu Lake had effects on Ca and Mg species. In the lake water, calcium carbonate was saturated or over saturated based on long-term statistical calculation of the saturation index (SI). On the sediment profiles, significant difference in Ca and Mg species existed between the surface sediment (0-10 cm) and deeper sediments (>10 cm). The interstitial water Ca2+ and Mg2+, ion-exchangeable Ca and Mg in the surface sediment were higher than those in the deeper sediment. In the spring, when the acid deposition is more intensive, the acid-extracted Ca and Mg in the surface sediment were lower than that in the deeper sediment in the northwest lake, due to carbonate dissolution caused by the regional acid deposition. Spatially, the higher concentration of acid-extracted Ca and Mg in the northwest surface sediment than that in the east lake was observed, indicating the pronounced carbonate biomineralization by algae bloom in the northwest lake. Statistical analysis showed that acid deposition exerted a stronger impact on the variation of acid-extracted Ca and Mg in the surface sediment than the biomineralization in Taihu Lake. For the total Ca and Mg concentration in the spring, however, no significant change between the surface and deeper sediment in the northwest lake was observed, indicating that the carbonate precipitation via biomineralization and the carbonate dissolution due to acidic deposition were in a dynamic balance. These features are of major importance for the understanding of combined effects of acid deposition and eutrophication on freshwater lakes. PMID- 27552996 TI - POPs in a major conurbation in Turkey: ambient air concentrations, seasonal variation, inhalation and dermal exposure, and associated carcinogenic risks. AB - Semi-volatile organic compounds were monitored over a whole year, by collection of gas and particle phases every sixth day at a suburban site in Izmir, Turkey. Annual mean concentrations of 32 polychlorinated biphenyls (?32PCBs) and 14 polycyclic aromatic hydrocarbons (?14PAHs) were 348 pg/m3 and 36 ng/m3, respectively, while it was 273 pg/m3 for endosulfan, the dominant compound among 23 organochlorine pesticides (OCPs). Monte Carlo simulation was applied to the USEPA exposure-risk models for the estimation of the population exposure and carcinogenic risk probability distributions for heating and non-heating periods. The estimated population risks associated with dermal contact and inhalation routes to ?32PCBs, ?14PAHs, and some of the targeted OCPs (alpha hexachlorocyclohexane (alpha-HCH), beta-hexachlorocyclohexane (beta-HCH), heptachlor, heptachlor epoxide, alpha-chlordane (alpha-CHL), gamma-chlordane (gamma-CHL), and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT)) were in the ranges of 1.86 * 10-16-7.29 * 10-9 and 1.38 * 10-10-4.07 * 10-6, respectively. The inhalation 95th percentile risks for ?32PCBs, ?14PAHs, and OCPs were about 6, 3, and 4-7 orders of magnitude higher than those of dermal route, respectively. The 95th percentile inhalation risk for ?32PCBs and OCPs in the non-heating period were 1.8- and 1.2-4.6 folds higher than in the heating period, respectively. In contrast, the 95th percentile risk levels for ?14PAHs in the heating period were 4.3 times greater than that of non-heating period for inhalation, respectively. While risk levels associated with exposure to PCBs and OCPs did not exceed the acceptable level of 1 * 10-6, it was exceeded for 47 % of the population associated with inhalation of PAHs with a maximum value of about 4 * 10-6. PMID- 27552997 TI - Steam reforming of ethanol for hydrogen production over Cu/Co-Mg-Al-based catalysts prepared by hydrotalcite route. AB - The performances of different 5Cu/CoxMg6-xAl2 (x = 0; 2; 4; 6) catalysts prepared by the wet impregnation method were investigated in the ethanol steam-reforming reaction (ESR) at 450 degrees C during 4 h under a steam/ethanol ratio of 3 (S/E = 3). The best catalyst among the prepared solids was 5Cu/Co6Al2 as it showed a complete ethanol conversion and the highest hydrogen and carbon dioxide productivities. However, following 50 h of aging, the catalyst deactivated due to the formation of a high amount of carbonaceous products detected by differential scanning calorimetry/thermogravimetry. On the other hand, the 5Cu/Co2Mg4Al2 catalyst showed a much lower quantity of coke deposition with no deactivation due to the basic character conferred by the magnesium oxide phase. PMID- 27552998 TI - Influence of alternating current on the adsorption of indigo carmine. AB - The main purpose of this work is to study the effect of a new process of accelerating which consist to couple the electrochemical process with the adsorption to remove an anionic dye, the indigo carmine. That is why, we investigated the effects of the new process of accelerating the adsorption process by using alternating current (AC) on the retention of an anionic dye, the indigo carmine. The adsorption capacity of dye (mg/g) was raised with the raise of current voltage in solution, temperature, and initial indigo carmine concentration and decreased with the increase of initial solution pH, current density, and mass of carbon. The results demonstrate that the removal efficiency of 97.0 % with the current voltage of 15 V is achieved at a current density of 0.014 A/cm2, of pH 2 using zinc as electrodes and contact time of 210 min for adsorption in the presence of AC. Concerning the adsorption without AC, the results obtained showed that for an initial concentration equal to 20 mg/L, more than 95 % amount of adsorbed dye was retained after 405 min of contact in batch system. The comparison between adsorption in the presence and absence of an alternating current shows the importance of the alternating current in the acceleration of the adsorption method and improve the performances of FILTRASORB 200. For both cases, the adsorption mechanism follows the fractal kinetics BSf(n,alpha) model and the Brouers-Sotolongo isotherm model provides a good fit of the experimental data for both adsorption with and without alternating current. PMID- 27552999 TI - Source-specific sewage pollution detection in urban river waters using pharmaceuticals and personal care products as molecular indicators. AB - Source-specific elucidation of domestic sewage pollution caused by various effluent sources in an urban river water, as conducted for this study, demands knowledge of the relation between concentrations of pharmaceuticals and personal care products (PPCPs) as molecular indicators (caffeine, carbamazepine, triclosan) and water quality concentrations of total nitrogen (T-N) and total phosphorous (T-P). River water and wastewater samples from the Asahikawa River Basin in northern Japan were analyzed using derivatization-gas chromatography/mass spectrometry. Caffeine, used as an indicator of domestic sewage in the Asahikawa River Basin, was more ubiquitous than either carbamazepine or triclosan (92-100 %). Its concentration was higher than any target compound used to assess the basin: <4.4-370 ng/L for caffeine, <0.6-3.9 ng/L for carbamazepine, and <1.1-13 ng/L for triclosan. Higher caffeine concentrations detected in wastewater effluents and the strongly positive mutual linear correlation between caffeine and T-N or T-P (R 2 > 0.759) reflect the contribution of septic tank system effluents to the lower Asahikawa River Basin. Results of relative molecular indicators in combination with different molecular indicators (caffeine/carbamazepine and triclosan/carbamazepine) and cluster analysis better reflect the contribution of sewage than results obtained using concentrations of respective molecular indicators and cluster analysis. Relative molecular indicators used with water quality parameters (e.g., caffeine/T-N ratio) in this study provide results more clearly, relatively, and quantitatively than results obtained using molecular indicators alone. Moreover, the caffeine/T N ratio reflects variations of caffeine flux from effluent sources. These results suggest strongly relative molecular indicators are also useful indicators, reflecting differences in spatial contributions of domestic sources for PPCPs in urban areas. PMID- 27553000 TI - Insights into aqueous carbofuran removal by modified and non-modified rice husk biochars. AB - Biochar has been considered as a potential sorbent for removal of frequently detected pesticides in water. In the present study, modified and non-modified rice husk biochars were used for aqueous carbofuran removal. Rice husk biochars were produced at 300, 500, and 700 degrees C in slow pyrolysis and further exposed to steam activation. Biochars were physicochemically characterized using proximate, ultimate, FTIR methods and used to examine equilibrium and dynamic adsorption of carbofuran. Increasing pyrolysis temperature led to a decrease of biochar yield and increase of porosity, surface area, and adsorption capacities which were further enhanced by steam activation. Carbofuran adsorption was pH dependant, and the maximum (161 mg g-1) occurred in the vicinity of pH 5, on steam-activated biochar produced at 700 degrees C. Freundlich model best fitted the sorption equilibrium data. Both chemisorption and physisorption interactions on heterogeneous adsorbent surface may involve in carbofuran adsorption. Langmuir kinetics could be applied to describe carbofuran adsorption in a fixed bed. A higher carbofuran volume was treated in a column bed by a steam-activated biochar versus non-activated biochars. Overall, steam-activated rice husk biochar can be highlighted as a promising low-cost sustainable material for aqueous carbofuran removal. PMID- 27553001 TI - Phytotoxicity of 15 common pharmaceuticals on the germination of Lactuca sativa and photosynthesis of Chlamydomonas reinhardtii. AB - Pharmaceuticals reach terrestrial environments through the application of treated wastewaters and biosolids to agricultural soils. We have investigated the toxicity of 15 common pharmaceuticals, classified as nonsteroidal anti inflammatory drugs (NSAIDs), blood lipid-lowering agents, beta-blockers and antibiotics, in two photosynthetic organisms. Twelve pharmaceuticals caused inhibitory effects on the radicle and hypocotyl elongation of Lactuca sativa seeds. The EC50 values obtained were in the range of 170-5656 mg L-1 in the case of the radicle and 188-4558 mg L-1 for the hypocotyl. Propranolol was the most toxic drug for both root and hypocotyl elongation, followed by the NSAIDs, then gemfibrozil and tetracycline. Other effects, such as root necrosis, inhibition of root growth and curly hairs, were detected. However, even at the highest concentrations tested (3000 mg L-1), seed germination was not affected. NSAIDs decreased the photosynthetic yield of Chlamydomonas reinhardtii, but only salicylic acid showed EC50 values below 1000 mg L-1. The first effects detected at low concentrations, together with the concentrations found in environmental samples, indicate that the use of biosolids and wastewaters containing pharmaceuticals should be regulated and their compositions assessed in order to prevent medium- and long-term impacts on agricultural soils and crops. PMID- 27553002 TI - A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China with very low 5-year survival rate mostly due to the paucity of effective early diagnostic methods. Serum autoantibodies against 9 tumor-associated antigens (TAAs) from ESCC patients and healthy controls were detected by enzyme linked immunosorbent assay to evaluate their performances in the immunodiagnosis of ESCC. Logistic regression models were generated to predict the probability of individuals being diagnosed with ESCC in training cohort (648 participants) and further validated in another independent cohort (372 participants). Finally, a panel of four TAAs showed high diagnostic accuracy with areas under the receiver operating characteristic curve of 0.838 in training cohort and 0.872 in validation cohort, respectively. The percentages of individuals correctly classified were 77.01 % in training cohort and 78.49 % in validation cohort, respectively. This model could discriminate early-stage (AJCC stage 0, I and II) ESCC patients from normal controls, with true-positive rate (TPR) of 67.57 % in training cohort and TPR of 63.33 % in validation cohort, and the overall TPR for early-stage ESCC was 66.85 % when the two cohorts were combined. The diagnostic performance of this model showed no significant difference between early-stage and late-stage (AJCC stage III and IV) ESCC patients. In summary, the optimized model with 4 TAAs has a high diagnostic performance for ESCC detection, especially for early-stage ESCC. PMID- 27553004 TI - Coverage, compliance, acceptability and feasibility of a program to prevent pre eclampsia and eclampsia through calcium supplementation for pregnant women: an operations research study in one district of Nepal. AB - BACKGROUND: Calcium supplementation during pregnancy has been shown to reduce the incidence of pre-eclampsia/eclampsia among women with low calcium intake. Universal free calcium supplementation through government antenatal care (ANC) services was piloted in the Dailekh district of Nepal. Coverage, compliance, acceptability and feasibility of the intervention were evaluated. METHODS: Antenatal care providers were trained to distribute and counsel pregnant women about calcium use, and female community health volunteers (FCHVs) were trained to reinforce calcium-related messages. A post-intervention cluster household survey was conducted among women who had given birth in the last six months. Secondary data analysis was performed using monitoring data from health facilities and FCHVs. RESULTS: One Thousand Two hundred-forty postpartum women were interviewed. Most (94.6 %) had attended at least one ANC visit; the median gestational age at first ANC visit was 4 months. All who attended ANC were counseled about calcium and received calcium tablets to take daily until delivery.79.5 % of the women reported consuming the entire quantity of calcium they received. The full course of calcium (300 tablets for 150 days) was provided to 82.3 % of the women. Consumption of the full course of calcium was reported by 67.3 % of all calcium recipients. Significant predictors of completing a full course were gestational age at first ANC visit and number of ANC visits during their most recent pregnancy (p < 0.01). Nearly all (99.2 %) reported taking the calcium as instructed with respect to dose, timing and frequency. Among women who received both calcium and iron (n = 1,157), 98.0 % reported taking them at different times of the day, as instructed. Over 97 % reported willingness to recommend calcium to others, and said they would like to use it during a subsequent pregnancy. There were no stock-outs of calcium. CONCLUSIONS: Calcium distribution through ANC was feasible and effective, achieving 94.6 % calcium coverage of pregnant women in the district. Most women (over 80 %) attended ANC early enough in pregnancy to receive the full course of calcium supplements and benefit from the intervention. High coverage, compliance, acceptability among pregnant women and feasibility were reported, suggesting that this intervention can be scaled up in other areas of Nepal. PMID- 27553005 TI - Genital trauma and vaginal bleeding: is it a lapse of time issue? A case report of a prepubertal girl and review of the literature. AB - Child victims of sexual abuse may present with physical findings whose interpretation requires the most exhaustive evaluation and an accurate collection of a detailed history. Genital bleeding is usually considered as an acute sign, related to a trauma that occurred shortly before its appearance. We report a case of a 34-month-old child who was referred to the emergency room with a significant vaginal hemorrhage, originating from a wide laceration of the posterior fourchette, and a negative history for accidental trauma. The characteristics of the lesion, compared to the temporal evolution of the healing process, and the witnesses' depositions led us to assume that the time elapsed between the abusive event and the physical examination was longer in respect to what had appeared at the first sight. The judicial reconstruction of the events confirmed our assumption, allowing the charge of the right abuse perpetrator. As the literature regarding this eventuality is very poor, we report this case to stress the importance for physicians to consider that an active bleeding may be the manifestation of a trauma that occurred very long before. PMID- 27553003 TI - Idiopathic Mediastinal Fibrosis: a Systemic Immune-Mediated Disorder. A Case Series and a Review of the Literature. AB - Mediastinal fibrosis is a rare disease characterised by fibrous proliferation in the mediastinum. It can be idiopathic or secondary to several conditions such as infections and malignancies. Anecdotal reports have described idiopathic mediastinal fibrosis (IMF) in association with other fibro-inflammatory or autoimmune diseases. We report nine new IMF cases recently seen at our Fibro Inflammatory Disease Clinic and reviewed the IMF cases reported in the English language literature throughout 2006-2016. The purposes of our literature search were to assess the frequency of the association between IMF and other immune mediated disorders and to analyse which disorders most often coexist with IMF. Of our nine IMF cases, one was associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, one with large-vessel arteritis, three with idiopathic retroperitoneal fibrosis (one of which was IgG4-related), one with pancreatitis and one with IgG4-related seminal vesicle involvement. The remaining two cases, in which IMF was not associated with any other disease, were both classifiable as IgG4-related. The literature review showed that, of the 84 IMF cases identified, 27 (32 %) were associated with other idiopathic autoimmune or fibro-inflammatory disorders, particularly small-vessel vasculitis, Behcet disease, retroperitoneal fibrosis and other conditions belonging to the IgG4 related disease spectrum. Based on our own data and the literature review, we conclude that IMF is often associated with other autoimmune or fibro-inflammatory diseases; therefore, its clinical management requires an accurate screening of associated conditions. Immune-mediated mechanisms may be shared by these disorders. PMID- 27553007 TI - Using digital technologies to engage with medical research: views of myotonic dystrophy patients in Japan. AB - BACKGROUND: As in other countries, the traditional doctor-patient relationship in the Japanese healthcare system has often been characterised as being of a paternalistic nature. However, in recent years there has been a gradual shift towards a more participatory-patient model in Japan. With advances in technology, the possibility to use digital technologies to improve patient interactions is growing and is in line with changing attitudes in the medical profession and society within Japan and elsewhere. The implementation of an online patient engagement platform is being considered by the Myotonic Dystrophy Registry of Japan. The aim of this exploratory study was to understand patients' views and attitudes to using digital tools in patient registries and engagement with medical research in Japan, prior to implementation of the digital platform. METHODS: We conducted an exploratory, cross-sectional, self-completed questionnaire with a sample of myotonic dystrophy (MD) patients attending an Open Day at Osaka University, Japan. Patients were eligible for inclusion if they were 18 years or older, and were diagnosed with MD. RESULTS: A total of 68 patients and family members attended the Open Day and were invited to participate in the survey. Of those, 59 % submitted a completed questionnaire (n = 40). The survey showed that the majority of patients felt that they were not receiving the information they wanted from their clinicians, which included recent medical research findings and opportunities to participate in clinical trials, and 88 % of patients indicated they would be willing to engage with digital technologies to receive relevant medical information. Patients also expressed an interest in having control over when and how they received this information, as well as being informed of how their data is used and shared with other researchers. CONCLUSION: Overall, the findings from this study suggest that there is scope to develop a digital platform to engage with patients so that they can receive information about medical care and research opportunities. While this study group is a small, self-selecting population, who suffer from a particular condition, the results suggest that there are interested populations within Japan that would appreciate enhanced communication and interaction with healthcare teams. PMID- 27553006 TI - ARFI: from basic principles to clinical applications in diffuse chronic disease-a review. AB - The many factors influencing the shear wave velocity (SWV) measured with Acoustic Radiation Force Impulse (ARFI) are examined in order to define the most correct examination technique. In particular, attention is given to the information achieved by experimental models, such as phantoms and animal studies. This review targets the clinical applications of ARFI in the evaluation of chronic diffuse disease, especially of liver and kidneys. The contribution of ARFI to the clinical workout of these patients and some possible perspectives are described. TEACHING POINTS: * Stiffness significantly varies among normal and abnormal biological tissues. * In clinical applications physical, geometrical, anatomical and physiological factors influence the SWV. * Elastographic techniques can quantify fibrosis, which is directly related to stiffness. * ARFI can be useful in chronic diffuse disease of liver and kidney. PMID- 27553008 TI - Mixed-Methods Evaluation of a Novel, Structured, Community-Based Support and Education Intervention for Individuals with HIV/AIDS in KwaZulu-Natal, South Africa. AB - People living with HIV in Sub-Saharan Africa face significant challenges accessing care. Community-based peer support groups can increase linkage to treatment, though the effectiveness of structured, scalable groups has not been demonstrated. This study aimed to measure the impact of the structured Integrated Access to Care and Treatment intervention on clients' knowledge, attitudes, and practice regarding HIV/AIDS, including their experiences of stigma, in KwaZulu Natal, South Africa. Data collection involved pre-/post-tests and client interviews. Pre-/post-test data from 66 clients were collected. 17 participants were interviewed. Paired t-tests did not detect significant changes in the main outcomes. Qualitative results suggested a psychosocial benefit as participants connected with their peers, expressed themselves openly, and re-engaged with their communities. Unfortunately, this study did not quantitatively measure psychosocial changes, and the results have limited generalizability to men. I ACT may be an effective complement to clinic-based support services, though further study should quantify the psychosocial benefit. PMID- 27553009 TI - Erratum to: Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial. PMID- 27553011 TI - Delivering on the Promise of Pheromones. PMID- 27553010 TI - A non-equivalent group pilot trial of a school-based physical activity and fitness intervention for 10-11 year old english children: born to move. AB - BACKGROUND: PE lessons are the formal opportunity in schools for promotion of physical activity and fitness. This study aimed to evaluate the effectiveness of a pilot PE intervention on physical activity, fitness, and psychosocial outcomes. METHODS: Participants were 139 children aged 10-11 years from four schools. For six weeks children in two schools received a twice-weekly pilot 'Born to Move' (BTM) physical activity (PA) and fitness intervention alongside one regular PE lesson. Children in the two comparison (COM) schools received their regular twice weekly PE lessons. Outcomes were lesson time and whole-day light (LPA), moderate (MPA), vigorous (VPA), and MVPA, and sedentary time, muscular fitness, cardiorespiratory fitness (CRF), and lesson-specific perceived exertion, enjoyment, and perceived competence. Outcomes were assessed at baseline (T0), midway through the intervention (T1), and at the end (T2) using ANOVAs and ANCOVAs. Intervention fidelity was measured using child and teacher surveys at T2 and analysed using Chi-square tests. RESULTS: The BTM group engaged in moderate PA for significantly more lesson time (29.4 %) than the COM group (25.8 %; p = .009, d = .53). The amount of moderate-to-vigorous PA (MVPA) during the T1 BTM lesson contributed 14.0 % to total MVPA, which was significantly more than the COM group's T1 PE lesson (11.4 %; p < .001, d = .47). The BTM group were significantly more active during the whole-day (p < .05) and the school-day (p < .01). In both groups push-up test performance increased (p < .001) and CRF test performance decreased (p < .01). Perceived exertion, enjoyment, and perceived competence increased in both groups (p < .05), but the BTM group rated their enjoyment of the T1 BTM lesson higher than the COM group rated their PE lesson (p = .02, d = .56). The children's and teachers' responses to the intervention indicated that the delivery aims of enjoyment, engagement, inclusivity, and challenge were satisfied. CONCLUSIONS: The BTM pilot programme has potential to positively impact on physical activity, fitness, and psychosocial outcomes. Further, BTM was enjoyed by the children, and valued by the teachers. This study can inform the design of a modified larger-scale cluster RCT evaluation. PMID- 27553012 TI - [Erratum to: "Choosing wisely" in infectious diseases : Overuse of antibiotics - too few vaccinations]. PMID- 27553013 TI - Rotational method simplifies 3-dimensional measurement of left atrial appendage dimensions during transesophageal echocardiography. AB - BACKGROUND: Not all echo laboratories have the capability of measuring direct online 3D images, but do have the capability of turning 3D images into 2D ones "online" for bedside measurements. Thus, we hypothesized that a simple and rapid rotation of the sagittal view (green box, x-plane) that shows all needed left atrial appendage (LAA) number of lobes, orifice area, maximal and minimal diameters and depth parameters on the 3D transesophageal echocardiography (3DTEE) image and LAA measurements after turning the images into 2D (Rotational 3DTEE/"Yosefy Rotation") is as accurate as the direct measurement on real-time-3D image (RT3DTEE). METHODS: We prospectively studied 41 consecutive patients who underwent a routine TEE exam, using QLAB 10 Application on EPIQ7 and IE33 3D-Echo machine (BORTHEL Phillips) between 01/2013 and 12/2015. All patients underwent 64 slice CT before pulmonary vein isolation or for workup of pulmonary embolism. LAA measurements were compared between RT3DTEE and Rotational 3DTEE versus CT. RESULTS: Rotational 3DTEE measurements of LAA were not statistically different from RT3DTEE and from CT regarding: number of lobes (1.6 +/- 0.7, 1.6 +/- 0.6, and 1.4 +/- 0.6, respectively, p = NS for all); internal area of orifice (3.1 +/- 0.6, 3.0 +/- 0.7, and 3.3 +/- 1.5 cm(2), respectively, p = NS for all); maximal LAA diameter (24.8 +/- 4.5, 24.6 +/- 5.0, and 24.9 +/- 5.8 mm, respectively, p = NS for all); minimal LAA diameter (16.4 +/- 3.4, 16.7 +/- 3.3, and 17.0 +/- 4.4 mm, respectively, p = NS for all), and LAA depth (20.0 +/- 2.1, 19.8 +/- 2.2, and 21.7 +/- 6.9 mm, respectively, p = NS for all). CONCLUSION: Rotational 3DTEE method for assessing LAA is a simple, rapid and feasible method that has accuracy similar to that of RT3DTEE and CT. Thus, rotational 3DTEE ("Yosefy rotation") may facilitate LAA closure procedure by choosing the appropriate device size. PMID- 27553014 TI - The efficacy of tolvaptan in the perioperative management of chronic kidney disease patients undergoing open-heart surgery. AB - PURPOSE: The perioperative management of chronic kidney disease (CKD) patients undergoing open-heart surgery is challenging. In this study, we evaluated the effects of tolvaptan in CKD patients after open-heart surgery. METHODS: Between 2010 to 2015, 731 patients underwent open-heart surgery in our hospital. We consecutively selected 71 patients with stage IIIa-IV CKD and divided them into two groups. Those who received tolvaptan postoperatively were defined as the "Tolvaptan group" (n = 25) and those who did not were defined as the "Non tolvaptan group" (n = 46). We compared the urine volume of postoperative days (POD) 1 and 2, the number of days to return to preoperative body weight (BW), and the change in the postoperative estimated glomerular filtration rate (eGFR). RESULTS: In the tolvaptan group, the urine volume was significantly larger (P = .04) and the duration to preoperative BW tended to be shorter. Overall, the postoperative change in the eGFR tended to be better in the tolvaptan group (P = .008). In particular, we found a significantly better trend in CKD stage IV (P = .04) patients and in the patients, whose cardiopulmonary bypass (CPB) time was longer than 120 min (P = .03). CONCLUSIONS: Tolvaptan can safely be used for CKD patients undergoing open-heart surgery and can provide a feasible urine volume without leading to a deterioration of their renal function. PMID- 27553015 TI - Parthenolide, an NF-kappaB Inhibitor Ameliorates Diabetes-Induced Behavioural Deficit, Neurotransmitter Imbalance and Neuroinflammation in Type 2 Diabetes Rat Model. AB - Diabetes is associated with behavioural and neurochemical alterations. In this manuscript, we are reporting the beneficial effects of parthenolide, an NF-kappaB inhibitor on behavioural and neurochemical deficits in type 2 diabetic rat model. Diabetes was induced by high-fat diet followed by low dose of streptozotocin (35 mg/kg). Elevated plus maze, open-field, MWM and passive avoidance test paradigm were used to assess behavioural and cognitive deficits. Three-week treatment of parthenolide (0.25 and 0.50 mg/kg; i.p.) attenuated diabetes-induced alteration in cognitive function in Morris water maze and passive avoidance test. Anxiety like behaviour was also reduced by parthenolide treatment. Moreover, TNF-alpha and IL-6 levels were significantly decreased in cortex and hippocampus of parthenolide-treated rats. Three-week parthenolide treatment also toned down the alteration of GABA and glutamate homoeostasis. Results of this study corroborate the involvement of neuroinflammation in the development of behavioural and neurochemical deficits in diabetic animals and point towards the therapeutic potential of parthenolide in diabetes-induced alteration of learning, memory and anxiety behaviour. PMID- 27553016 TI - Medical comorbidity of binge eating disorder. AB - PURPOSE: To gain further understanding of the general medical comorbidity of binge eating disorder (BED) beyond its association with obesity. METHOD: We reviewed studies of general medical comorbidity in people with BED or clinically significant binge eating behavior beyond obesity. We also reviewed studies of BED in specific medical conditions. RESULTS: Three broad study categories of medical comorbidity in BED were found: cross-sectional studies of medical conditions in BED; prospective studies of medical conditions in BED; and studies of BED in specific medical conditions. Cross-sectional epidemiologic data suggest that BED is associated with medical conditions related to obesity, including diabetes, hypertension, dyslipidemias, sleep problems/disorders, and pain conditions, and that BED may be related to these conditions independent of obesity and co occurring psychiatric disorders. Prospective data suggest that BED may be associated with type 2 diabetes and metabolic syndrome. BED or binge eating behavior is also associated with asthma and gastrointestinal symptoms and disorders, and among women, menstrual dysfunction, pregnancy complications, intracranial hypertension, and polycystic ovary syndrome. CONCLUSIONS: BED is associated with substantial medical comorbidity beyond obesity. Further study of the general medical comorbidity of BED and its relationship to obesity and co occurring psychiatric disorders is greatly needed. PMID- 27553018 TI - Tuberculosis and its Treatment: An Overview. AB - Tuberculosis (TB) is a primordial infectious disease that mainly affects the lungs. M. tuberculosis (Mycobacterium tuberculosis) is the etiological agent of TB and currently more than one-third of the world population is suffering from TB. For the treatment of TB, administration of multiple antibiotics such as isoniazid, rifampicin, pyrazinamide and ethambutol is required for a long period of time to kill bacteria. However, antibiotic resistance is an emerging problem in multiple drug-resistant tuberculosis (MDR-TB) infections. World Health Organization (WHO) has developed a novel strategy called DOTS (directly observed treatment, short-course), in which specific combination of anti-TB drugs is given to control TB. In this review article we have focused on the comprehensive management of TB and have provided the valuable information about first and second line anti-TB drugs, DOTS and novel drug delivery systems to be used against M. tuberculosis. Important aspects related to new anti-TB drugs and vaccines in various stages of clinical development are also covered in this article. PMID- 27553019 TI - Recent Developments of Metal and Metal Oxide Nanocatalysts in Organic Synthesis. AB - Recently, various nanomaterials have been used in many organic transformations as efficient catalysts. The development of new catalysts by nanoscale design has emerged as a fertile field for research and innovation. The ability of nanotechnology to enhance catalytic activity opens the potential to replace expensive catalysts with lower amounts of inexpensive nanocatalysts. Besides, development of efficient and environmentally friendly synthetic methodologies for the synthesis of compound libraries of medicinal scaffolds is an attractive area of research in both academic and pharmaceutical industry. According to above reports and needs, this review deals with applications of nanoparticles as catalysts in various organic syntheses. We detail the topic of organic transformations using nanoparticles: Metal Nanoparticles and Metal Oxide Nanoparticles. In the latter part, different Metal Oxide Nanoparticles, such as ZnO Nanoparticle, TiO2 Nanoparticle, and CuO Nanoparticle are discussed. PMID- 27553017 TI - Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. AB - Vitamin D is a fat-soluble vitamin and a steroid hormone that plays a central role in maintaining calcium-phosphorus and bone homeostasis in close interaction with parathyroid hormone, acting on its classical target tissues, namely, bone, kidney, intestine, and parathyroid glands. However, vitamin D endocrine system regulates several genes (about 3 % of the human genome) involved in cell differentiation, cell-cycle control, and cell function and exerts noncalcemic/pleiotropic effects on extraskeletal target tissues, such as immune and cardiovascular system, pancreatic endocrine cells, muscle, and adipose tissue. Several studies have demonstrated the role of vitamin D supplementation in the prevention/treatment of various autoimmune diseases and improvement of glucose metabolism, muscle, and adipose tissue function. Hence, this review aims to elucidate the effects of vitamin D on extraskeletal target tissues and to investigate the potential therapeutic benefit of vitamin D supplementation among a broad group of pathological conditions, especially with regard to metabolic and autoimmune diseases. In addition, we focused on the best daily intakes and serum levels of vitamin D required for extraskeletal benefits which, even if still controversial, appear to be higher than those widely accepted for skeletal effects. PMID- 27553020 TI - The diagnostic challenge of salivary gland malignancies. PMID- 27553021 TI - SPG46 and SPG56 are rare causes of hereditary spastic paraplegia in China. PMID- 27553022 TI - Nucleophosmin: from structure and function to disease development. AB - Nucleophosmin (NPM1) is a critical cellular protein that has been implicated in a number of pathways including mRNA transport, chromatin remodeling, apoptosis and genome stability. NPM1 function is a critical requirement for normal cellular biology as is underlined in cancer where NPM1 is commonly overexpressed, mutated, rearranged and sporadically deleted. Consistent with a multifunctional role within the cell, NPM1 can function not only as a proto-oncogene but also as a tumor suppressor. The aim of this review is to look at the less well-described role of NPM1 in the DNA repair pathways as well as the role of NPM1 in the regulation of apoptosis and its mutation in cancers. PMID- 27553023 TI - DDB2 increases radioresistance of NSCLC cells by enhancing DNA damage responses. AB - Radiotherapy resistance is one of the major factors limiting the efficacy of radiotherapy in lung cancer patients. The extensive investigations indicate the diversity in the mechanisms underlying radioresistance. Here, we revealed that DNA damage binding protein 2 (DDB2) is a potential regulator in the radiosensitivity of non-small cell lung cancer (NSCLC) cells. DDB2, originally identified as a DNA damage recognition factor in the nucleotide excision repair, promotes the survival and inhibits the apoptosis of NSCLC cell lines upon ionizing radiation (IR). Mechanistic investigations demonstrated that DDB2 is able to facilitate IR-induced phosphorylation of Chk1, which plays a critical role in the cell cycle arrest and DNA repair in response to IR-induced DNA double strand breaks (DSBs). Indeed, knockdown of DDB2 compromised the G2 arrest in the p53-proficient A549 cell line and reduced the efficiency of homologous recombination (HR) repair. Taken together, our data indicate that the expression of DDB2 in NSCLC could be used as a biomarker to predict radiosensitivity of the patients. Targeting Chk1 can be used to increase the efficacy of radiotherapy in patients of NSCLC possessing high levels of DDB2. PMID- 27553024 TI - Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis. AB - Paraoxonase (PON) enzymes possess antioxidant properties and protect against cardiovascular diseases. As a member of PON family, PON3 is primarily synthesized in the liver and poorly investigated. This study aimed to examine the expression of PON3 in human hepatocellular carcinoma (HCC) and investigate the clinical significance and biological function of PON3 in HCC patients. We first analyzed PON3 expression in 50 paired HCC samples (HCC tissues vs matched para-cancerous tissues) and 160 clinical HCC specimens by using immunohistochemistry (IHC). Our results showed that the expression of PON3 was downregulated in HCC and significantly associated with tumor-node-metastasis (TNM) stage, tumor size, and tumor number. Kaplan-Meier survival and Cox regression analyses showed that PON3 was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR). Finally, we aimed to reveal the biological function of PON3 in HCC growth and metastasis, and our results showed that overexpression of PON3 potently inhibited growth and metastasis of HCC. Collectively, our study demonstrated that PON3 exhibited tumor-suppressive effects toward HCC and it might serve as a novel prognostic marker in HCC. PMID- 27553025 TI - Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells. AB - Increasing evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in colorectal cancer (CRC); however, only few CRC-related lncRNAs have been characterized. In this study, we aimed to dig out potential dysregulated lncRNAs that are highly involved in CRC development. Using a lncRNA-mining approach, we performed lncRNA expression profiling in a large CRC cohort from Gene Expression Ominus (GEO), GSE39582 test series (N = 585). We identified 31 downregulated lncRNAs and 16 upregulated lncRNAs from the GSE39582 test series patients (566 tumor patients and 19 normal controls). The reliability of lncRNA expression profiles was further confirmed by RT-qPCR in carcinoma tissues and paired adjacent normal tissues from 30 CRC patients, also in the serum from 109 CRC patients, and 99 normal individuals. We demonstrated that the expression of SLC25A25-AS1, which has not been reported previously, was significantly decreased in both the tumor tissues (27 out of 30) and serum of CRC patients. SLC25A25-AS1 overexpression significantly inhibited proliferation and colony formation in colorectal cancer cell lines, and downregulation of SLC25A25-AS1 obviously enhanced chemoresistance and promoted EMT process in vitro associated with Erk and p38 signaling pathway activation. Therefore, SLC25A25-AS1 was determined to play a tumor suppressive role in CRC. Our results might provide a lncRNA-based target for CRC treatment. PMID- 27553027 TI - Psychosocial and Behavioral Characteristics of High-Risk Men Who Have Sex with Men (MSM) of Unknown HIV Positive Serostatus in Bangkok, Thailand. AB - HIV prevalence remains high in men who have sex with men (MSM) in Bangkok. Even though resources for HIV testing and treatment are available for all, a large proportion of MSM still do not get HIV tested. We studied high risk MSM who are unaware of their HIV status to help maximize effectiveness of our resources. Convenience sampling was conducted among MSM who came for HIV testing at the Thai Red Cross Anonymous Clinic and two popular drop-in centers in Bangkok. Inclusion criteria were MSM aged >18 years, have not been tested positive for HIV, who reported >=1 of the following in the previous 6 months: condomless sex with a male, being a sex worker, or having a sexual transmitted infection diagnosis. Audio-Computer-Assisted Self-Interview was used to assess psychosocial profile, sexual risks, and HIV testing patterns prior to being informed of their HIV positive status. Among 499 high-risk MSM enrolled, the median age was 24.8 years and 112 (22 %) tested HIV-positive. Among the HIV-positive participants, 92 % self-identified as gay (versus bisexual), 39 % attained a bachelors degree or higher, 65 % had monthly income 10,000-29,999 baht ($280-830 USD), 10 % had vaginal or anal sex with a woman in the past 12 months, 39 % had condomless receptive sex with men and 21 % went to Lat Phrao to find a sexual partner. Compared to HIV negative MSM, HIV-positive MSM had less HIV testing: 31 % had ever been tested for HIV, 12 % had been tested in the past 6 months; but were more likely to guess correctly their positive status (31 %). Regarding psychosocial variables among HIV-positive MSM, 7 % had regular methamphetamine use in the past 3 months, 10 % had >2 sources of discrimination, and 8 % had >2 sources of discrimination due to being MSM. In multivariable model, age<30 year old, self-identified as gay, had monthly income <50,000 baht ($1400 USD), had anal sex with men in past 12 months, had >2 sources of discrimination because of being MSM, did not get HIV test in past 6 months, and guess of positive HIV were significantly associated with HIV positive status. Young MSM with lower socioeconomic status (SES) should be prioritized for innovative approaches to promoting awareness and uptake of HIV testing. Societal stigmatization of MSM should be addressed as a potential barrier to uptake of voluntary HIV testing. Resilience factors among these marginalized MSM who still test frequently and remain HIV-negative despite residing in a context with community viral loads and discrimination should also be studied in order to curb the HIV epidemic in Bangkok. PMID- 27553026 TI - A randomized controlled trial comparing in-person and wiki-inspired nominal group techniques for engaging stakeholders in chronic kidney disease research prioritization. AB - BACKGROUND: Few studies have evaluated stakeholder engagement in chronic kidney disease (CKD) research prioritization. In this two-arm, parallel group randomized controlled trial, we sought to compare an in-person nominal group technique (NGT) approach with an online wiki-inspired alternative to determining the top 10 CKD research priorities, and to evaluate stakeholder engagement and satisfaction with each process. METHODS: Eligible participants included adults >=18 years with access to a computer and Internet, high health literacy, and from one of the following stakeholder groups: patients with CKD not on dialysis, their caregivers, health care providers who care for patients with CKD, or CKD-related health policymakers. Fifty-six participants were randomized to a wiki-inspired modified NGT that occurred over 3 weeks vs. a 1-day in-person NGT workshop, informed by James Lind Alliance methodology, to determine the top 10 CKD-related research priorities. The primary outcome was the pairwise agreement between the two groups' final top 10 ranked priorities, evaluated using Spearman's correlation coefficient. Secondary outcomes included participant engagement and satisfaction and wiki tool usability. RESULTS: Spearman's rho for correlation between the two lists was 0.139 (95 % confidence interval -0.543 to 0.703, p = 0.71), suggesting low correlation between the top 10 lists across the two groups. Both groups ranked the same item as the top research priority, with 5 of the top 10 priorities ranked by the wiki group within the top 10 for the in-person group. In comparison to the in-person group, participants from the wiki group were less likely to report: satisfaction with the format (73.7 vs.100 %, p = 0.011); ability to express their views (57.9 vs 96.0 %, p = 0.0003); and perception that they contributed meaningfully to the process (68.4 vs 84.0 %, p = 0.004). CONCLUSIONS: A CKD research prioritization approach using an online wiki-like tool identified low correlation in rankings compared with an in-person approach, with less satisfaction and perceptions of active engagement. Modifications to the wiki-inspired tool are required before it can be considered a potential alternative to an in-person workshop for engaging patients in determining research priorities. TRIAL REGISTRATION: ( ISRCTN18248625 ). PMID- 27553028 TI - Identity Conflict and Sexual Risk for Black and Latino YMSM. AB - Young (aged 18-30) Black and Latino men who have sex with men are at a higher risk of contracting HIV than their White counterparts. In order to better understand the unique nature of sexual risk-taking, we examined the extent to which ethnic group, ethnic identity, and sexual pride predicted condomless anal sex with casual partners among 161 young men who have sex with men (YMSM) who identify as Black or Latino. Negative binomial regressions were conducted using a cross-sectional design. Sexual pride was a negative predictor of condomless anal sex across all participants, but this effect was moderated by ethnic exploration and ethnic group; the relationship between sexual pride and condomless anal sex was strengthened by greater ethnic exploration among Latino YMSM, and weakened by greater ethnic exploration among Black YMSM. Implications for intersectional identity, identity conflict, and HIV prevention among young gay men of color are discussed. PMID- 27553029 TI - The Impact of Positive Income Shocks on Risky Sexual Behavior: Experimental Evidence from Tanzania. AB - In this paper, we exploit a lottery in Tanzania, which randomly assigned eligible participants to receive $100 cash grants. The randomized nature of the lottery allows us to estimate the causal impact of positive income shocks on risky sexual behavior. We found that winning the lottery led men to have 0.28 (95 % CI 0.14, 0.55) more sexual partners and to a 0.21 (95 % CI 0.01-0.4) increase in the probability of unprotected sex with a non-primary partner relative to a control group of eligible non-winners. We found no significant effect of winning the lottery on the sexual behavior of women. PMID- 27553031 TI - Green Synthesis, Optical, Structural, Photocatalytic, Fluorescence Quenching and Degradation Studies of ZnS Nanoparticles. AB - The study describes a simple hydrothermal method for the synthesis of zinc sulfide nanoparticles (ZnS NPs) using bovine serum albumin (BSA). The synthesized NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), fluorescence, UV-visible diffuse reflectance spectra (DRS) and zeta potential techniques. The morphologies and sizes were characterized by SEM and TEM. The size of ZnS NPs was observed with an effective diameter size of 20 nm. The photocatalytic activity of ZnS NPs was evaluated by the degradation of rhodamine B (RB) dye under sunlight irradiation. The degradation reaction follows the pseudo-first order kinetics. In addition, the fluorescence quenching and binding of ZnS NPs with crystal violet (CV) molecules have been studied. The binding constant (Ka) between ZnS NPs and CV is calculated using modified Stern-Volmer equation. The photocatalytic degradation and kinetics of CV dye by ZnS NPs in the presence of UV light has been investigated using spectrofluorometer. PMID- 27553030 TI - Maternal Influences on Access to and Use of Infant ARVs and HIV Health Services in Uganda. AB - Vertical transmission of HIV is responsible for about 14 % of new HIV cases reported each year in sub-Saharan Africa. Barriers that prevent women from accessing and using antiretroviral medications (ARVs) for themselves and their infants perpetuate the epidemic. To identify influences on access to and use of infant HIV health services, specifically nevirapine administration, we conducted a mixed methods study among HIV-positive women in Uganda. This included a cross sectional survey (n = 384) and focus group discussions (n = 6, 5-9 participants each). Of the 384 women, 80 % gave nevirapine to their infants within 72 h of birth. Factors independently associated with nevirapine administration were lack of maternal adherence to ARVs (AOR 3.55, 95 % CI 1.36-9.26) and attending a support group (AOR 2.50, 95 % CI 1.06-5.83). Non-health facility births were inversely related to nevirapine use (AOR 0.02, 95 % CI 0.003-0.09). Focus group discussions identified four themes impacting access and use: attending a support group, health care worker attitudes, lack of partner support, and poor health messaging regarding ARVs. Improving health care worker messaging regarding ARVs and providing women with needed support to access and use infant ARV prophylaxis is critical to overcoming access barriers. Eliminating these barriers may prevent numerous HIV infections each year saving the lives of many HIV-exposed infants. PMID- 27553032 TI - Sex Disparities in Ischemic Stroke Care: FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). AB - BACKGROUND AND PURPOSE: Sex-specific disparities in stroke care including thrombolytic therapy and early hospital admission are reported. In a large registry of Florida and Puerto Rico hospitals participating in the Get With The Guidelines-Stroke program, we sought to determine sex-specific differences in ischemic stroke performance metrics and overall thrombolytic treatment. METHODS: Around 51 317 (49% women) patients were included from 73 sites from 2010 to 2014. Multivariable logistic regression with generalized estimating equations evaluated sex-specific differences in the prespecified Get With The Guidelines-Stroke metrics for defect-free care in ischemic stroke, adjusting for age, race ethnicity, insurance status, hospital characteristics, individual risk factors, and the presenting stroke severity. RESULTS: As compared with men, women were older (73+/-15 versus 69+/-14 years; P<0.0001), more hypertensive (67% versus 63%, P<0.0001), and had more atrial fibrillation (19% versus 16%; P<0.0001). Defect-free care was slightly lower in women than in men (odds ratio, 0.96; 95% confidence interval, 0.93-1.00). Temporal trends in defect-free care improved substantially and similarly for men and women, with a 29% absolute improvement in women (P<0.0001) and 28% in men (P<0.0001), with P value of 0.13 for time-by-sex interaction. Women were less likely to receive thrombolysis (odds ratio, 0.92; 95% confidence interval, 0.86-0.99; P=0.02) and less likely to have a door-to needle time <1 hour (odds ratio, 0.83; 95% confidence interval, 0.71-0.97; P=0.02) as compared with men. CONCLUSIONS: Women received comparable stroke care to men in this registry as measured by prespecified Get With The Guidelines metrics. However, women less likely received thrombolysis and had door-to-needle time <1 hour, an observation that calls for the implementation of interventions to reduce sex disparity in these measures. PMID- 27553033 TI - Adolescents' psychological health during the economic recession: does public spending buffer health inequalities among young people? AB - BACKGROUND: Many OECD countries have replied to economic recessions with an adaption in public spending on social benefits for families and young people in need. So far, no study has examined the impact of public social spending during the recent economic recession on health, and social inequalities in health among young people. This study investigates whether an increase in public spending relates to a lower prevalence in health complaints and buffers health inequalities among adolescents. METHODS: Data were obtained from the 2009/2010 "Health Behaviour in School-aged Children (HBSC)" study comprising 11 - 15-year old adolescents from 27 European countries (N = 144,754). Socioeconomic position was measured by the Family Affluence Scale (FAS). Logistic multilevel models were conducted for the association between the absolute rate of public spending on family benefits per capita in 2010 and the relative change rate in family benefits (2006-2010) in relation to adolescent psychological health complaints in 2009/2010. RESULTS: The absolute rate of public spending on family benefits in 2010 did not show a significant association with adolescents' psychological health complaints. Relative change rates of public spending on family benefits (2006-2010) were related to better health. Greater socioeconomic inequalities in psychological health complaints were found for countries with higher change rates in public spending on family benefits (2006-2010). CONCLUSIONS: The results partially support our hypothesis and highlight that policy initiatives in terms of an increase in family benefits might partially benefit adolescent health, but tend to widen social inequalities in adolescent health during the recent recession. PMID- 27553034 TI - The Validity of the Comparative Interrupted Time Series Design for Evaluating the Effect of School-Level Interventions. AB - OBJECTIVE: In this article, we examine whether a well-executed comparative interrupted time series (CITS) design can produce valid inferences about the effectiveness of a school-level intervention. This article also explores the trade-off between bias reduction and precision loss across different methods of selecting comparison groups for the CITS design and assesses whether choosing matched comparison schools based only on preintervention test scores is sufficient to produce internally valid impact estimates. RESEARCH DESIGN: We conduct a validation study of the CITS design based on the federal Reading First program as implemented in one state using results from a regression discontinuity design as a causal benchmark. RESULTS: Our results contribute to the growing base of evidence regarding the validity of nonexperimental designs. We demonstrate that the CITS design can, in our example, produce internally valid estimates of program impacts when multiple years of preintervention outcome data (test scores in the present case) are available and when a set of reasonable criteria are used to select comparison organizations (schools in the present case). PMID- 27553036 TI - Chondrosarcoma of the para-acetabulum: correlation of imaging features with histopathological grade. AB - OBJECTIVE: To evaluate the computed tomography (CT) and magnetic resonance (MR) imaging features of para-acetabular chondrosarcoma (CS) and assess the difference between low-grade CS (LGCS) and high-grade CS (HGCS). MATERIALS AND METHODS: Thirty-one patients with histopathologically confirmed central para-acetabular CSs (6 LGCS and 25 HGCS) were retrospectively reviewed. Image features were evaluated for the following: cortical destruction, tumor border and pattern, calcification mode, soft-tissue mass, density/signal intensity, peritumoral edema, acetabular (cartilage) destruction, diffuse signal changes in acetabulum, mass inside hip joint, femoral head involvement, enhancement manifestations and the maximum length of the tumor. These image features between LGCS and HGCS were also assessed. RESULTS: The most common CT and/or MR findings included cortical destruction, punctate, ring-and-arc and linear calcification, soft-tissue mass, lobulated border, high signal intensity with low signal septa on T2-weighted image, peritumoral edema, hip joint infiltration, peripheral and septal enhancement on post-enhanced MR image. Statistical analysis showed that the image features, such as cortical destruction, soft-tissue mass, hip joint infiltration and tumor size were significantly different between LGCS and HGCS (p < 0.05). CONCLUSION: The characteristic radiological features of para-acetabular CSs are osteolytic lesions with cortical destruction, soft-tissue mass, lobulated border, calcification, and high signal intensity with low signal septa on T2-weighted MR image, peripheral and septal enhancement on post-enhanced MR image. Cortical destruction, soft-tissue mass, hip joint infiltration and tumor size can differentiate HGCS from LGCS. PMID- 27553035 TI - Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons. AB - BACKGROUND: Alterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown. METHODS: In this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes. RESULTS: We demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells. CONCLUSIONS: Lmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated. PMID- 27553037 TI - Predictive Validity of Curriculum-Embedded Measures on Outcomes of Kindergarteners Identified as At Risk for Reading Difficulty. AB - This study examined the predictive validity of formative assessments embedded in a Tier 2 intervention curriculum for kindergarten students identified as at risk for reading difficulty. We examined when (i.e., months during the school year) measures could predict reading outcomes gathered at the end of kindergarten and whether the predictive validity of measures changed across the kindergarten year. Participants consisted of 137 kindergarten students whose reading development was assessed four times from October to February. Measures aligned with content taught in the curriculum and assessed a range of phonologic, alphabetic, and word reading skills. Results from structural equation modeling indicate that 36.3% to 65.2% of the variance was explained on the latent decoding outcome and 62.0% to 86.8% on the latent phonological outcome across the four time points. Furthermore, the predictive validity of specific skills increased over the kindergarten year, with more complicated tasks (e.g., word segmentation) becoming more predictive at subsequent measurement occasions. Results suggest that curriculum-embedded measures may be viable tools for assessing and predicting reading performance. PMID- 27553038 TI - Drug prices are kept high in US by protection and price negotiations, study finds. PMID- 27553039 TI - Wnt3a nanodisks promote ex vivo expansion of hematopoietic stem and progenitor cells. AB - BACKGROUND: Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound palmitoleoyl moiety in the N terminal domain. RESULTS: By combining murine Wnt3a with phospholipid and apolipoprotein A-I, ternary complexes termed nanodisks (ND) were generated. ND associated Wnt3a is soluble in the absence of detergent micelles and gel filtration chromatography revealed that Wnt3a co-elutes with ND. In signaling assays, Wnt3a ND induced beta-catenin stabilization in mouse fibroblasts as well as hematopoietic stem and progenitor cells (HSPC). Prolonged exposure of HSPC to Wnt3a ND stimulated proliferation and expansion of Lin(-) Sca-1(+) c-Kit(+) cells. Surprisingly, ND lacking Wnt3a contributed to Lin(-) Sca-1(+) c-Kit(+) cell expansion, an effect that was not mediated through beta-catenin. CONCLUSIONS: The data indicate Wnt3a ND constitute a water-soluble transport vehicle capable of promoting ex vivo expansion of HSPC. PMID- 27553040 TI - Nurr1 promotes intestinal regeneration after ischemia/reperfusion injury by inhibiting the expression of p21 (Waf1/Cip1). AB - : Intestinal ischemia/reperfusion (I/R) injury is a potentially life-threatening condition that can cause injuries to remote organs at the end stage. The damage caused by intestinal I/R insult induces changes in the barrier functions of the intestine, and the intrinsic mechanism of regeneration is often insufficient to restore barrier functions, as indicated by the high mortality rate of patients experiencing intestinal I/R injury. However, little is known about the mechanisms of intestinal regeneration after I/R injury. Here, we reported that nuclear receptor-related protein 1 (Nurr1), a nuclear orphan receptor, was induced during intestinal regeneration after I/R. Our findings showed that Nurr1 expression was consistent with the expression of Ki-67 and phosphorylated histone H3 (pH 3) in the intestine after I/R injury. Nurr1 knockdown led to G1-phase arrest mediated by p21 (Waf1/Cip1) activation, but Nurr1 overexpression reduced the proportion of IEC-6 cells in G1 phase as a result of p21 inhibition in a p53-independent manner. Using chromatin immunoprecipitation assays, luciferase assays, and mutational analysis, we demonstrated that Nurr1 directly inhibited the transcription of p21. These results define a novel Nurr1/p21 pathway that is involved in intestinal regeneration after I/R injury. These findings provide novel molecular insights into the pathogenesis of intestinal regeneration after I/R and possibly support the development of new potential therapies for intestinal I/R injury. KEY MESSAGE: Nurr1 was induced during intestinal regeneration after I/R injury. Nurr1 promoted proliferation of intestinal epithelial cells after H/R injury. Nurr1 inhibited p21 expression in a p53 independent manner. Nurr1 inhibited p21 gene transcription by binding to p21 promoter directly. PMID- 27553042 TI - Association Between Vaginal Douching and Genital Human Papillomavirus Infection Among Women in the United States. AB - The very few studies that have examined the association between vaginal douching and genital human papillomavirus (HPV) infection have found contrary results. We investigated the associations between douching and numbers of HPV genotypes infecting 1271 participants aged 20-49 years in the 2003-2004 US National Health and Nutrition Examination Survey. After controlling for relevant covariates, douching in the past 6 months was significantly associated with infection by higher numbers of all genital HPV types (relative risk ratio, 1.26; 95% confidence interval, 1.03-1.54) and HPV high-risk types (1.40; 1.09-1.80). PMID- 27553041 TI - BRCA1-associated protein 1 deficiency in lung adenocarcinoma predicts poor outcome and increased tumor invasion. AB - BACKGROUND: The major pathological type of non-small cell lung cancer is lung adenocarcinoma (LAC), which has a poor prognosis. BRCA1-associated protein-1 (BAP1) is a newly identified tumor suppressor that regulates a number of cellular functions in somatic malignancies. However, the impact of BAP1 expression in LAC has not been investigated. METHODS: A total of 112 cases of LAC and 101 cases of non-neoplastic lung diseases were included in this study. The study focused on BAP1 expression in lung tissues and its relationship to patients' clinical and pathological features. BAP1 expression was detected by immunohistochemistry. A human LAC cell line NCI-H1299 was transfected with lipofectamine p3xFLAG-BAP1. BAP1 gene expression was silenced in another LAC cell line NCI-H1650, in order to test the inhibitory effect of BAP1 on cell migration and invasion, as well as cell cycle regulation. RESULTS: BAP1 expression showed a negative correlation with tumorigenesis of LAC (p <0.001) and lymph node metastasis (p = 0.010). High expression of BAP1 predicted longer disease free survival (p = 0.040) and overall survival (p = 0.021) of LAC patients. In functional assays, BAP1 was found to inhibit the migration and invasion of LAC cells, and promoted their apoptosis and necrosis. CONCLUSIONS: We identify BAP1 as a LAC precursor as well as a robust prognostic indicator in LAC patients. This study provides in vitro rationale for the further investigation of BAP1 in preclinical studies. PMID- 27553043 TI - Humans Can Taste Glucose Oligomers Independent of the hT1R2/hT1R3 Sweet Taste Receptor. AB - It is widely accepted that humans can taste mono- and disaccharides as sweet substances, but they cannot taste longer chain oligo- and polysaccharides. From the evolutionary standpoint, the ability to taste starch or its oligomeric hydrolysis products would be highly adaptive, given their nutritional value. Here, we report that humans can taste glucose oligomer preparations (average degree of polymerization 7 and 14) without any other sensorial cues. The same human subjects could not taste the corresponding glucose polymer preparation (average degree of polymerization 44). When the sweet taste receptor was blocked by lactisole, a known sweet inhibitor, subjects could not detect sweet substances (glucose, maltose, and sucralose), but they could still detect the glucose oligomers. This suggests that glucose oligomer detection is independent of the hT1R2/hT1R3 sweet taste receptor. Human subjects described the taste of glucose oligomers as "starchy," while they describe sugars as "sweet." The dose-response function of glucose oligomer was also found to be indistinguishable from that of glucose on a molar basis. PMID- 27553044 TI - Impact of Pulmonary Artery Catheter Use on Short- and Long-Term Mortality in Patients with Cardiogenic Shock. AB - OBJECTIVES: The impact of pulmonary artery catheterization (PAC) on survival in patients with cardiogenic shock (CS) is not well established. This study aimed to assess whether Swan-Ganz catheter monitoring is related to short- and long-term mortality in patients with CS. METHODS: One hundred and twenty-nine consecutive patients with a first admission for CS were prospectively enrolled in a single center registry between December 2005 and May 2009, and were subsequently followed up over 5.3 years. RESULTS: PAC was used in 64% of all patients with a mean age of 68 years (65% men). After adjustment for age, gender and the presence of CS upon admission, PAC was associated with lower short-term mortality [hazard ratio (HR) = 0.55, 95% confidence interval (CI) 0.35-0.86, p = 0.008] as well as lower mortality rates in the long-term follow-up (HR = 0.63, 95% CI 0.41-0.97, p = 0.035). In a subgroup analysis, the use of PAC was associated with reduced mortality in patients without acute coronary syndrome (ACS), i.e. 49% in the Swan Ganz group vs. 82% (p = 0.010), but there was no difference within the ACS group. CONCLUSIONS: The use of PAC in patients with CS was associated with lower short- and long-term mortality rates after adjustment for age, gender and the presence of shock upon admission. This benefit was only significant in those patients without ACS. PMID- 27553045 TI - Serum Anti-Mullerian Hormone Concentration in Young Women with Chronic Kidney Disease on Hemodialysis, and After Successful Kidney Transplantation. AB - BACKGROUND/AIMS: In women with chronic kidney disease (CKD) fertility abnormalities occur frequently. Anti-Mullerian hormone (AMH) inhibits excessive recruitment of primordial follicles. The aim of the study was to evaluate the serum AMH concentration in women on hemodialysis and after kidney transplantation (KTx). METHODS: 46 hemodialysed women and 14 with CKD about to undergo kidney transplantation were enrolled into the study. The control group consisted of 40 healthy women. In all subjects serum concentration of AMH was determined (in chronic hemodialysis women and in control group once, and in women after KTx immediately before surgery, and 3 times after the transplantation). RESULTS: Serum AMH concentration in hemodialysed women and in the control group did not differ significantly, while in hemodialysed women with regular menstrual cycles it was significantly lower than in the control group: 2.20 (1.08-3.55ng/ml) and 3.30 (1.80-6.10ng/ml) respectively, (p=0.02). In the KTx group, a significant decrease in serum AMH concentration was found from 3.30ng/ml (2.20-6.50ng/ml) at baseline to 1.90ng/ml (1.30-2.40ng/ml) at 6 months after KTx (p=0.007). CONCLUSIONS: 1. Significantly lower serum AMH concentration was found in the regularly menstruating CKD women on hemodialysis in comparison with the healthy controls. 2. Serum AMH decreased significantly after successful KTx. PMID- 27553046 TI - Shrinkage stress kinetics of Bulk Fill resin-based composites at tooth temperature and long time. AB - OBJECTIVE: To determine the shrinkage stress kinetics at up to 12h after light exposure and at tooth temperature during placement of selected Bulk Fill resin based composites (RBCs). METHODS: Five representative Bulk Fill RBCs from four companies were chosen with a wide range of viscosity and filler volume content. The shrinkage stress kinetics at T=33 degrees C was measured continuously over a period of 12h using a modified tensometer with the ability to measure the cantilever beam deflection to better than 40nm accuracy at a sampling rate of up to 200 samples/s, and thermally stable resulting in a measurement accuracy better than 0.05MPa at 12h. The tensometer compliance was 0.105MUm/N. A custom made heater was used to control the RBC sample temperature at T=33 degrees C with a temperature gradient across the sample of less than 1 degrees C. The samples were irradiated for 20s with irradiance of 1.1W/cm2 and total energy density of 22J/cm2. Three samples (n=3) were used for each RBCs. RESULTS: The shrinkage stress at 12h for the five Bulk Fill RBCs ranged from 2.21 to 3.05MPa, maximum stress rate ((dS/dt)M) varied from 0.18 to 0.41MPa/s, time at which the maximum stress rate occurred (tMax) were between 1.42 to 3.24s and effective gel time (tgel) varied from 50 to 770ms. Correlations were observed between (dS/dt)M and tMax (r=-0.946), tMax and filler volume fraction (r=-0.999), and between the shrinkage stress at 12h and tgel (r=0.994). However, no correlation was observed between the stress at 12h and filler volume fraction. SIGNIFICANCE: The shrinkage stress for four of the five Bulk Fill RBCs were not significantly different (p<0.05) at 6h and beyond after photo-curing and that fully developed stress induced by photo-cured RBCs may only be reached at times longer than 12h. PMID- 27553047 TI - Aging gracefully in Greater Beirut: are there any gender-based differences? AB - Background: The implications of rapid aging of the Lebanese population are under researched. No national studies have so far investigated the living conditions and the health status of urban Lebanese elderly across gender. This was a cross sectional study involving 905 randomly selected community dwelling elderly aged >=65 years living in Greater Beirut. Gender differences were assessed among participants who completed a standardized questionnaire on socio-demographic factors, nutritional, health, and functional characteristics. The sample included 533 men (59%) and 372 women (41%). Elderly were regrouped into 'younger elderly' (<=70 years), and 'older elderly' (>70 years) which represented respectively 44.3% and 55.7% of the total population. Women, regardless of their age, were less educated and more likely to live alone. Moreover, poor nutritional status, self-perceived health, absence of physical activity, comorbidity, polymedication and depression were significantly higher among women. 'Older elderly' women became significantly more functionally disabled compared with men of their age. This study evidenced that Lebanese elderly women were disadvantaged regarding their socio-economic, health and functional status. It is requested a nationwide effort to improve the socio-economic status and the health of Lebanese elderly, especially women. PMID- 27553048 TI - In vitro performance of the fixed and adjustable gravity-assisted unit with and without motion-evidence of motion-induced flow. AB - BACKGROUND: Anti-siphon devices and gravitational-assisted valves have been introduced to counteract the effects of overdrainage after implantation of a shunt system. The study examined the flow performance of two gravitational assisted valves (shunt assistant - SA and programmable shunt assistant - proSA, Miethke & Co. KG, Potsdam, Germany) in an in vitro shunt laboratory with and without motion. METHODS: An in vitro laboratory setup was used to model the cerebrospinal fluid (CSF) drainage conditions similar to a ventriculo-peritoneal shunt and to test the SA (resistance of +20 cmH2O in 90 degrees ) and proSA (adjustable resistance of 0 to +40 cmH2O in 90 degrees ). The differential pressure (DP) through the simulated shunt and tested valve was adjusted between 0 and 60 cmH2O by combinations of different inflow pressures (40, 30, 20, 10, and 0 cmH2O) and the hydrostatic negative outflow pressure (0, -20, and -40 cmH2O) in several differing device positions (0 degrees , 30 degrees , 60 degrees , and 90 degrees ). In addition, the two devices were tested under vertical motion with movement frequencies of 2, 3, and 4 Hz. RESULTS: Both gravity-assisted units effectively counteract the hydrostatic effect in relation to the chosen differential pressure. The setting the proSA resulted in flow reductions in the 90 degrees position according to the chosen resistance of the device. Angulation related flow changes were similar in the two devices in 30-90 degrees position, however, in the 0-30 degrees position, a higher flow is seen in the proSA. Repeated vertical movement significantly increased flow through both devices. While with the proSA a 2-Hz motion was not able to induce additional flow (0.006 +/- 0.05 ml/min), 3- and 4-Hz motion significantly induced higher flow values (3 Hz: +0.56 +/- 0.12 ml/min, 4 Hz: +0.54 +/- 0.04 ml/min). The flow through the SA was not induced by vertical movements at a low DP of 10 cmH2O at all frequencies, but at DPs of 30 cmH2O and higher, all frequencies significantly induced higher flow values (2 Hz: +0.36 +/- 0.14 ml/min, 3 Hz: +0.32 +/- 0.08 ml/min, 4 Hz: +0.28 +/- 0.09 ml/min). CONCLUSIONS: In a static setup, both tested valves effectively counteracted the hydrostatic effect according to their adjusted or predefined resistance in vertical position. Motion-induced increased flow was demonstrated for both devices with different patterns of flow depending on applied DP and setting of the respective valve. The documented increased drainage should be considered when selecting appropriate valves and settings in very active patients. PMID- 27553049 TI - The lymph nodes of the central compartment during autoimmune chronic thyroiditis: incidence and ultrasonographic aspects. PMID- 27553050 TI - Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy. AB - The therapeutic activity of 131I administered to patients with Graves' disease can be calculated by means of Marinelli's formula. The thyroidal iodine uptake (131IUmax) needed for the calculation is usually determined with the use of 131I. The purpose of the paper was to estimate 131IUmax on the basis of technetium uptake in the thyroid at 20 min (99mTcU20min). Eighty patients suffering from Graves' disease were qualified for radioiodine therapy with measurement of fT4, fT3, thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. 131IUmax for each patient was determined according to the levels of 131I after 24 h (131IU24h), while effective half-life (T eff) according to the measurements of 131IU24h and 131I uptake after 48 h (131IU48h). Additionally, on the day before measuring 131IU24h, 99mTcU20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p < 0.05, between the following pairs of values: TRAb and 131IU24h, TRAb and 99mTcU20min, and 99mTcU20min and 131IU24h. The interdependence between 131IU24h and 99mTcU20min at the level of significance p < 0.05 is described by the following algorithms: 131IU24h = 17.72 * ln (99mTcU20min) + 30.485, if TRAb < 10 IU/ml, and 131IU24h = 18.03 * ln (99mTcU20min) + 38.726, if TRAb > 10 IU/ml. It is possible to predict thyroid iodine uptake 131IU24h in Graves' disease on the basis of measuring the uptake of 99mTcU20min. This shortens the time necessary for diagnosis and enables the calculation of 131I activity using Marinelli's formula. PMID- 27553051 TI - Intracameral cefuroxime in the prevention of postoperative endophthalmitis: an experience from Hong Kong. AB - PURPOSE: The purpose was to study the effect of introducing intracameral cefuroxime, which was compounded by a hospital pharmacy, on postoperative endophthalmitis in a tertiary eye centre in Hong Kong. METHODS: All cases that underwent cataract surgeries over a 12-year period (January 2004 to December 2015) were included. The routine use of intracameral cefuroxime at the end of cataract surgery was introduced at our centre after April 2010. All cefuroxime aliquots were prepared by the hospital pharmacy using an aseptic compounding technique. The rates of postoperative endophthalmitis before April 2010 (Group 1, no intracameral cefuroxime) and after April 2010 (Group 2, routine use of intracameral cefuroxime) were compared. RESULTS: A total of 30,428 eyes (7,332 in Group 1 and 23,096 in Group 2) were studied. Eight cases developed postoperative endophthalmitis (1.09 in 1000; 0.11 %) in Group 1 whereas no cases developed endophthalmitis (0 %) in Group 2. The rate of reduction was statistically significant (p < 0.0001). Seven out of eight cases of endophthalmitis were confirmed by positive culture. Organisms identified were Group G Streptococcus (two cases), Group B Streptococcus, Staphylococcus aureus, Serratia marcescens, and coagulase-negative Staphylococcus (two cases). Antibiotic susceptibility testing results were available in six cases. Four out of six organisms were susceptible to the penicillin group. No adverse events related to the use of intracameral cefuroxime were encountered. CONCLUSIONS: The use of intracameral cefuroxime could significantly reduce the rate of postoperative endophthalmitis in a tertiary centre in Hong Kong. The use of aseptic compounding to prepare cefuroxime aliquots by hospital pharmacy appeared to be safe and efficacious. PMID- 27553052 TI - Impact of allergy and atopy on the risk of pseudophakic cystoid macular edema. AB - PURPOSE: To assess the risk of pseudophakic cystoid macular edema (PCME) following cataract surgery in patients with allergies and/or atopic disorders. PATIENTS AND METHODS: Medical records of 3,850 consecutive eyes that underwent cataract surgery were retrospectively reviewed for prevalence of allergies and atopic status and development of PCME. Patients with any known risk factors for PCME were excluded. Macular examination was performed using spectral-domain optical coherence tomography (SD-OCT) before and at 4, 8, 12, 16, 24, and 36 weeks after surgery. If both eyes in one patient underwent cataract surgery, one eye was randomly selected. Odds ratios and confidence intervals were estimated. RESULTS: Out of 240 patients enrolled in this series, 65 patients (27.1 %) showed positive allergic status, 19 patients (7.9 %) suffered from atopic syndromes, and 11 (4.6 %) showed both (allergies and atopic diseases). PCME occurred in eight patients (12.3 %) of the allergy cohort, whereas no patient (0 %) of the atopy cohort developed PCME. The risk of PCME was comparable in patients with allergies or atopic diseases to patients without allergies or atopy (allergy: p = 0.635; odds ratio (OR) 1.303, 95 % confidence interval (CI) 0.461-3.398; atopy: p = 0.234; OR 0.000, 95 % CI 0-1.815). CONCLUSION: Positive status of allergy or atopy does not seem to increase the risk of PCME. Therefore, postoperative treatment after cataract surgery does not have to be modified in allergic or atopic patients. PMID- 27553053 TI - No Disparity for American Indians in Surgery for Pelvis/Lower Extremity Fractures: a Cohort Study of the National Trauma Data Bank (NTDB). AB - BACKGROUND: Racial/ethnic disparities in trauma care have been reported. The American Indian/Alaska Native (AI/AN) population faces a twofold to fourfold increase of risk for traumatic injury. We hypothesized that surgical intervention and time to surgery were associated with race/ethnicity, specifically AI/AN compared to other race/ethnicity groups with open pelvic and lower extremity fractures (OPLEFx). METHODS: Non-AI/AN racial/ethnic groups were compared to AI/ANs among adults aged 15 years and older using the National Trauma Data Bank for 2008-2012. OPLEFx were identified via ICD-9-CM. Predictors of surgery and time to surgery were modeled via logistic regression and survival analyses. RESULTS: AI/AN patients (2.7 %, n = 206) were younger (36 +/- 16 versus 41 +/- 18 years, p < 0.001) and more likely to have Medicaid and other government insurance. There were no differences in AI/ANs versus non-AI/ANs undergoing surgery (88.4 versus 86.8 %, respectively) or time to surgery (11.7 +/- 25.3 versus 12.0 +/- 22.5 h, respectively). Injury severity was predictive of surgery in all six models (OR = 0.04 to 0.32). A race-gender interaction increased odds of surgery in the AI/AN versus all other races model (OR = 3.58, 95 % CI 1.18 10.84) and in three of five pairwise models. Median time to surgery varied by race, favoring AI/ANs with least preoperative time. CONCLUSION: The AI/AN population experienced no disparities in rate of, or time to, OPLEFx surgery. Race-specific predictors for surgery included gender, probability of death, and multiple fractures. More study is warranted to ameliorate trauma care disparities and achieve reasonably equitable care as demonstrated in AI/ANs with OPLEFx. PMID- 27553054 TI - Analysis of Race and Time to Antibiotics Among Patients with Severe Sepsis or Septic Shock. AB - BACKGROUND/OBJECTIVES: The objective of this study is to investigate potential racial disparities in time to antibiotics among patients presenting to the emergency department (ED) with severe sepsis or septic shock. METHODS: This was a retrospective observational study of adults >18 years with severe sepsis or septic shock presenting to a large, urban, academic ED and admitted to the ICU from 10/2005 to 2/2012. Time to antibiotic data was abstracted by ICU research staff; other data were abstracted by blinded trained research assistants using standardized abstraction forms. Time from ED arrival to antibiotics was compared in white vs. non-white patients using cumulative events curves followed by Cox proportional hazards regression, controlling for age, gender, ethnicity, source of infection, and SOFA score. RESULTS: Seven hundred sixty-eight patients were included; 19.5 % (n = 150) were non-white. Median minutes to antibiotics was 131 in white patients vs. 158 in non-white patients (p = 0.03, log-rank test). The unadjusted hazard ratio for non-white patients was 0.82 (95 %CI 0.58-0.98). After adjustment, the hazard ratio for race was not significant (0.90, 95 %CI 0.73 1.10). CONCLUSIONS: In a single-center sample of patients with severe sepsis or septic shock, adjustment for factors including age and infectious source eliminated the difference in time to antibiotics by race. Further research should investigate disparities in sepsis care between hospitals with differing patient populations. PMID- 27553055 TI - Association Between Self-Esteem and Depressive Symptoms Is Stronger Among Black than White Older Adults. AB - BACKGROUND: Although poor self-esteem is a core component of depression, we still do not know if racial and ethnic groups differ in the magnitude of this link. This study compared Black and White older adults on the association between self esteem and depressive symptoms. METHODS: With a cross-sectional design, this study enrolled 1493 older individuals (age 66 or more) from the 2001 Religion, Aging, and Health Survey, a nationally representative study in the United States. Participants were either Blacks (n = 734) or Whites (n = 759). Depressive symptoms and self-esteem were measured using brief measures of the Center for Epidemiological Studies-Depression scale (CES-D) and the Rosenberg Self-Esteem Scale, respectively. Demographics, socioeconomics, and self-rated health (SRH) were covariates and self-identified race was the moderator. Linear regression models were used for data analysis. RESULTS: Low self-esteem was associated with more depressive symptoms (B = 0.17, 95 % CI 0.15-0.28), above and beyond all covariates. We found a significant and positive interaction between race (Black) and poor self-esteem on depressive symptoms (B = 0.34, 95 % CI 0.17-0.36), suggesting a stronger association between self-esteem and depressive symptoms among Blacks compared to Whites. Although low self-esteem is associated with higher depressive symptoms in both Whites and Blacks (p < 0.05 for both races), the standardized coefficient was 0.25 (95 % CI = 0.20-0.43) for Blacks and 0.16 (95 % CI = 0.09-0.29) for Whites. CONCLUSIONS: Low self-esteem and high depressive symptoms are more closely associated among Blacks than Whites. It is not clear whether depression leaves a larger scar on self-esteem for Blacks, or Blacks are more vulnerable to the effect of low self-esteem on depression. PMID- 27553056 TI - How often is the office visit needed? Predicting total knee arthroplasty revision risk using pain/function scores. AB - BACKGROUND: Most patients have favorable outcomes after primary total knee arthroplasty (TKA). Well-validated methods to predict the risk of poor outcomes have not been developed or implemented. Several patients have annual clinic visits despite well-funcitoning TKA, as a routine practice, to detect early failure requiring revision surgery. It is not known whether assessment of pain and function can be used as a predictive tool for early failure and revision to guide practice. Our objective was to determine whether pain and function can predict revision after TKA. METHODS: We retrospectively studied data from a large prospectively gathered TKA registry to examine changes in outcome scores for primary TKAs undergoing revision compared to those not requiring revision to determine the factors that are predictive for revision. RESULTS: Of the 1,012 patients, 721 had had a single-sided primary TKA and had American Knee Society (AKS) Scores for three or more visits. 46 patients underwent revision, 23 acutely (fracture, traumatic component failure or acute infection) and 23 for latent causes (late implant loosening, progressive osteolysis, or pain and indolent infection). Mean age was 70 years for the non-revision patients, and 64 years for those revised. Both AKS Clinical and AKS Function Scores for non-revised patients were higher than in revision patients, higher in acute revision compared to latent revision patients. Significant predictors of revision surgery were preoperative, 3- and 15-month postoperative AKS Clinical Scores and 3-month AKS Function Scores. At 15-month post-TKA, a patient with a low calculated probability of revision, 32 % or less, was unlikely to require revision surgery with a negative predictive value of 99 %. CONCLUSION: Time dependent interval evaluation post-TKA with the AKS outcome scores may provide the ability to assign risk of revision to patients at the 15-month follow-up visit. If these findings can be replicated using a patient-reported measure, a virtual follow-up with patient-reported outcomes and X-ray review may be an alternative to clinic visit for patients doing well. PMID- 27553057 TI - Estrogen and Microbiota Crosstalk: Should We Pay Attention? AB - Recent advances have suggested that steroid hormones such as estrogens, and gut microbiota might synergize to influence obesity, diabetes, and cancer. We discuss recent knowledge of the interactions between estrogens and gut microbiota, and new insights that might offer new approaches to influence this crosstalk and improve metabolic outcomes. PMID- 27553058 TI - The Impact of Weight Labels on Body Image, Internalized Weight Stigma, Affect, Perceived Health, and Intended Weight Loss Behaviors in Normal-Weight and Overweight College Women. AB - PURPOSE: To explore the psychological impact of weight labels. DESIGN: A double blind experiment that randomly informed participants that they were "normal weight" or "overweight." SETTING: Public university in Honolulu, Hawai'i. PARTICIPANTS: Normal-weight and overweight female undergraduates (N = 113). MEASURES: The Body Image States Scale, Stunkard Rating Scale, Weight Bias Internalization Scale, Positive and Negative Affect Schedule, General Health question from the 12-item Short Form Health Survey, modified version of the Weight Loss Methods Scale, and a manipulation check. ANALYSIS: A 2 * 2 between subjects analysis of variance explored the main effects of the assigned weight label and actual weight and interactions between assigned weight label and actual weight. RESULTS: Significant main effects of the assigned weight label emerged on measures of body dissatisfaction, F(1, 109) = 12.40, p = .001, [Formula: see text] = 0.10, internalized weight stigma, F(1, 108) = 4.35, p = .039, [Formula: see text] = .04, and negative affect, F(1, 108) = 9.22, p = .003, [Formula: see text] = .08. Significant assigned weight label * actual weight interactions were found on measures of perceived body image, F(1, 109) = 6.29, p = .014, [Formula: see text] = .06, and perceived health, F(1, 109) = 4.18, p = .043, [Formula: see text] = .04. CONCLUSION: A weight label of "overweight" may have negative psychological consequences, particularly for overweight women. PMID- 27553059 TI - Socioecological Risk Predictors of Physical Activity and Associated Mortality. AB - PURPOSE: To assess (1) the cumulative effect of socioecological factors (social risk) on objectively measured physical activity, (2) the cumulative socioecological risk on all-cause mortality, (3) the potential interaction effects of social risk factors on physical activity and mortality, and (4) whether physical activity mediates the relationship between social risk and mortality. DESIGN: Cross-sectional and prospective. SETTING: Laboratory- and survey-based testing of the general US population. PARTICIPANTS: Five thousand five hundred seventy-four adult participants of the National Health and Nutrition Examination Survey 2003 to 2006. MEASURES: Social risk was assessed from 4 variables, namely poverty level, education, minority status, and social living status. Moderate-to-vigorous physical activity (MVPA) was assessed via accelerometry. Mortality was assessed via linkage with the National Death Index, with follow-up through 2011. ANALYSIS: Negative binomial regression and Cox proportional hazard model. RESULTS: Compared to those with 0 social risk factors, those with 1 and 2+ social risk factors engaged in 11% and 10% less MVPA, respectively. Those with 1 (vs 0) social risk factor had a 2.0-fold increase in mortality risk, and those with 2+ (vs 0) social risk factors had a 2.3-fold increase in mortality risk. Interaction effects for various socioecological factors on both MVPA and mortality were observable. CONCLUSION: Cumulative social risk is associated with less MVPA and increased all-cause mortality risk. Given the interaction effects of socioecological factors, targeted interventions in identified populations may be needed. PMID- 27553060 TI - Alpha 5/6 helix domains together with N-terminus determine the apoptotic potency of the Bcl-2 family proteins. AB - A critical process in apoptosis is the permeabilization of the mitochondrial outer membrane (MOM). This process is known to be regulated by the multi-domain Bcl-2 family proteins. For example, the pro-apoptotic proteins Bax and Bak are responsible for forming pores at MOM. The anti-apoptotic proteins (including Bcl 2, Mcl-1 and Bcl-xL), on the other hand, can inhibit this pore-forming process. Interestingly, although these two subgroups of proteins perform opposite apoptotic functions, their structures are very similar. This raises two highly interesting questions: (1) Why do these structurally similar proteins play opposite roles in apoptosis? (2) What are the roles of different functional domains of a Bcl-2 family protein in determining its apoptotic property? In this study, we generated a series of deletion mutants and substitution chimera, and used a combination of molecular biology, bio-informatics and living cell imaging techniques to answer these questions. Our major findings are: (1) All of the Bcl 2 family proteins appear to possess an intrinsic pro-apoptotic property. (2) The N-termini of these proteins play an active role in suppressing their pro apoptotic function. (3) The apoptotic potency is positively correlated with membrane affinity of the alpha 5/6 helix domains. (4) Charge distribution flanking the alpha 5/6 helices is also important for the apoptotic potency. These findings explain why different members of Bcl-2 family proteins with similar domain composition can function oppositely in the apoptotic process. PMID- 27553061 TI - Editorial (Thematic Issue: Cellular and Biochemical Effects of Microcystins (Cyanobacterial Toxins) and Their Potential Medical Consequences). PMID- 27553062 TI - Minimally invasive transaxial lumbosacral interbody fusion: a ten year single centre experience. AB - PURPOSE: Our aim was to evaluate mid- and long-term results in a cohort of patients who underwent minimally invasive transaxial lumbosacral fixation and to identify clinical and other parameters that can aid in proper patient selection. METHODS: Over a period of ten years, we assessed 164 patients who had a complete follow-up of a minimum of one year (average 54 months). On follow-up, we recorded clinical status, fusion status, visual analogue scale (VAS), Oswestry Lower Back Pain Disability Index (ODI) scores and patient satisfaction. RESULTS: There were no intra- or peri-operative complications. Overall clinical success rate was 73.8 %. Only sex (female), working status (still working), body mass index (BMI) (lower) and presence of Modic II changes (absent) were correlated with a good result. CONCLUSIONS: Transaxial fixation is a safe, minimally invasive technique that can offer good results in patients with single-level degenerative disc disease (DDD) at the lumbosacral level, with minimal operative risk. PMID- 27553064 TI - Whole body PET/CT in the follow-up of asymptomatic patients with stage IIB-IIIB cutaneous melanoma. AB - BACKGROUND: Whole body positron emission tomography (PET)/computed tomography (CT) is a sensitive imaging technique in patients with metastatic melanoma, but its role in the follow-up of asymptomatic high-risk patients is unclear. The aim was to study the role of PET/CT as a routine surveillance imaging tool in asymptomatic high-risk patients at the early stage of follow-up combined with a sufficient follow-up over several years. MATERIAL AND METHODS: A total of 110 asymptomatic patients with clinically local American Joint Committee on Cancer (AJCC) stage IIB-IIIB melanoma underwent routine whole body PET/CT scanning after a mean interval of seven months after initial surgery. Clinical data were retrospectively analyzed after a median follow-up time of 4.6 years. RESULTS: Recurrent melanoma was detected in 45 patients (41%) and 36 (33%) died of melanoma. In 11 asymptomatic patients (10%) occult disease was detected with a single PET/CT. In seven of these patients (64%), positive PET/CT finding had major influence in treatment decisions. Four patients underwent surgical metastasectomy and two of them remained disease-free. In 34 patients (31%) PET/CT revealed no disease, but recurrence was detected at a median time of 19 months after negative PET/CT scan. In 50 patients (45%) PET/CT finding was true negative. In 15 patients (14%) scan was false positive leading to additional management or repetitive imagings. CONCLUSION: A single PET/CT could detect 24% of all recurrences in asymptomatic melanoma patients at the early stage of follow up, but an earlier detection of occult metastases did not improve survival. PMID- 27553063 TI - The immunology of post-kala-azar dermal leishmaniasis (PKDL). AB - Post-kala-azar dermal leishmaniasis (PKDL) is a common complication of visceral leishmaniasis (VL) caused by Leishmania donovani. Because of its possible role in transmission it is considered a public health problem in VL endemic areas. The clinical features include a skin rash consisting of macules, papules or nodules in an otherwise healthy individual; this presentation is determined by the immune response towards parasites in the skin that probably persisted from the previous VL episode. The immune response in VL, cured VL and PKDL is the result of changes in the cytokine profile that only in part can be captured under the Th1 and Th2 dichotomy. Regulatory T cells and Th 17 cells also play a role. VL is characterized by an absent immune response to Leishmania with a predominantly Th2 type of response with high levels of IL-10; after successful treatment the patient will be immune with in vitro features of a Th1 type of response and in vivo a positive leishmanin skin test. PKDL takes an intermediate position with a dissociation of the immune response between the skin and the viscera, with a Th2 and Th1 type of response, respectively. It is likely that immune responses determine the different epidemiological and clinical characteristics of PKDL in Asia and Africa; various risk factors for PKDL may influence this, such as incomplete and inadequate treatment of VL, parasite resistance and genetic factors. It should be noted that PKDL is a heterogeneous and dynamic condition and patients differ with regard to time of onset after visceral leishmaniasis (VL), chronicity, extent and appearance of the rash including related immune responses, all of which may vary over time. Better understanding of these immune responses may offer opportunities for manipulation including combined chemotherapy and immunotherapy for VL to prevent PKDL from occurring and similarly in the treatment of chronic or treatment resistant PKDL cases. PMID- 27553065 TI - A novel Glycine soja homeodomain-leucine zipper (HD-Zip) I gene, Gshdz4, positively regulates bicarbonate tolerance and responds to osmotic stress in Arabidopsis. AB - BACKGROUND: Wild soybean (Glycine soja) is a highly adaptive plant species which can grow well in saline-alkaline soils. In soybean genome, there exist about 140 HD-Zip (Homeodomain-leucine Zipper) genes. HD-Zip transcription factor family is one of the largest plant specific superfamilies and plays important roles in response to abiotic stresses. Although HD-Zip transcription factors have been broadly reported to be involved in plant resistance to abiotic stresses like salt and drought, their roles in response to bicarbonate stress is largely unknown. RESULTS: From our previous transcriptome profile analysis of wild soybean treated by 50 mM NaHCO3, we identified an HD-Zip gene (Gshdz4) which showed high response to the alkaline stress. Our result of qRT-PCR showed that the expression of Gshdz4 was induced by alkaline stress (NaHCO3) in both leaves and roots of wild soybean. Overexpression of Gshdz4 in Arabidopsis resulted in enhanced tolerance to NaHCO3 and KHCO3 during the process of plant growth and development. However, the growths of transgenic and WT plants were not significantly different on the medium with high pH adjusted by KOH, implicating Gshdz4 is only responsible for resisting HCO3 (-) but not high pH. The transgenic plants had less MDA contents but higher POD activities and chlorophyll contents than the WT plants. Moreover, the transcript levels of stress-related genes, such as NADP-ME, H (+) -Ppase, RD29B and KIN1 were increased with greater extent in the transgenic plants than the wild plants. On the contrary, Gshdz4 overexpression lines were much sensitive to osmotic stress at seed germination and stocking stages compared to the wild plants. CONCLUSIONS: We revealed that the important and special roles of Gshdz4 in enhancing bicarbonate tolerance and responding to osmotic stress. It is the first time to elucidate these novel functions of HD-ZIP transcription factors. All the evidences broaden our understanding of functions of HD-Zip family and provide clues for uncovering the mechanisms of high tolerance of wild soybean to saline-alkaline stresses. PMID- 27553067 TI - CCGs vary widely in how well they deliver healthcare, new measure shows. PMID- 27553066 TI - Cost-Effectiveness of Insulin Degludec/Insulin Aspart Versus Biphasic Insulin Aspart in Patients with Type 2 Diabetes from a Danish Health-Care Perspective. AB - INTRODUCTION: To evaluate the cost-effectiveness of the co-formulation insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart (BIAsp 30), both administered twice daily, in patients with type 2 diabetes mellitus (T2DM), using a short-term cost-effectiveness model. METHODS: Data from two phase 3a treat-to target clinical trials were used to populate a simple and transparent short-term cost-effectiveness model. The costs and effects of treatment with IDegAsp versus BIAsp 30 were calculated over a 5-year period, from a Danish health-care cost perspective. One-way and probabilistic sensitivity analyses were conducted to assess the degree of uncertainty and robustness of the results. RESULTS: The base case incremental cost-effectiveness ratio (ICER) of 81,507.91 Danish Kroner (DKK) per quality-adjusted life year (QALY) demonstrates that IDegAsp is a cost effective treatment compared with BIAsp 30, over a 5-year time horizon. One-way sensitivity analyses show that the ICERs remain within an acceptable range when the rates of hypoglycemia, unit cost of hypoglycemia, disutilities of hypoglycemic events, and the time horizon are varied, ranging from 71,012 DKK to 209,446 DKK. The probabilistic sensitivity analysis demonstrates that the probability that IDegAsp is cost-effective relative to BIAsp 30 is 99.50%, assuming a cost-effectiveness threshold of 250,000 DKK per QALY. CONCLUSION: This short-term cost-effectiveness model shows that IDegAsp is a cost-effective treatment compared with BIAsp 30 for patients with T2DM. This result is primarily driven by significant reductions in severe hypoglycemia and insulin dose observed with IDegAsp versus BIAsp 30. Sensitivity analyses demonstrate the robustness of these results. FUNDING: Novo Nordisk A/S, Soborg, Denmark. PMID- 27553068 TI - Herpes zoster laryngitis in a patient treated with fingolimod. AB - Development of treatment with immunomodulatory agents has improved prognosis of various autoimmune-related diseases. A sphingosin-1-phosphate receptor modulator, or fingolimod, is the first licensed oral drug for relapsing-remitting multiple sclerosis. The agent reduces circulating lymphocytes by trapping T cells in lymph nodes, possibly leading to reactivation of latent viruses. A 41-year-old Japanese woman who had been treated with fingolimod for 2 years presented with unilateral sore throat. Laryngoscopy revealed exudates unilaterally emerging on the left side of her supraglottic region. Serum level of the varicella zoster virus (VZV) specific IgG was markedly elevated, and a result of genome sequence using the exudates demonstrated VZV as a possible causative pathogen. Fingolimod therapy was discontinued and the patient was successfully treated with intravenous acyclovir. This is the first reported case of fingolimod-associated herpes zoster laryngitis, in which the local VZV reactivation was demonstrated by next generation sequencing technology. The present case highlights that the occurrence of VZV reactivation should be recalled in any patients undergoing fingolimod therapy. PMID- 27553069 TI - Bacteremia due to Citrobacter braakii: A case report and literature review. AB - Among the Citrobacter genus, the most commonly isolated bacteria from human specimens are Citrobacter freundii and Citrobacter koseri, and previous cases of infection due to Citrobacter braakii have been rarely reported. We present a case of bacteremia due to C. braakii in a 38-year-old woman with cervical cancer. She was admitted to our hospital with complaints of a fever, chills, and nausea. Blood culture results showed gram-negative bacilli identified as C. braakii via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, although biochemical testing findings were suggestive of C. freundii. Since a rare pathogen was detected in the present case and the results of additional biochemical studies were suggestive of both C. braakii and Citrobacter farmeri, genetic analysis was conducted. Finally, the gram-negative bacilli were confirmed as C. braakii, a member of the C. freundii complex since 1993, by 16S ribosomal RNA gene sequencing analysis. The gastrointestinal tract was considered the portal of entry, because the patient had a rectal fistula and other cultures such as urine and vaginal discharge incubated species other than C. braakii. The patient recovered after receiving treatment with ciprofloxacin for 14 days. The epidemiology and clinical characteristics of C. braakii infection are still unknown because of the limitations in accurate identification by using currently available commercial biochemical testing and previously, only 6 cases of C. braakii infection have been reported. Physicians should focus on this species, because it causes community-acquired infections, although further studies are needed to clarify the clinical characteristics of C. braakii infections. PMID- 27553070 TI - Are all fosfomycins alike? PMID- 27553071 TI - A fatal case of streptococcal toxic shock syndrome caused by Streptococcus suis carrying tet (40) and tet (O/W/32/O), Italy. AB - We report the first human fatal case of streptococcal toxic shock syndrome (STSS) caused by Streptococcus suis serotype 2 carrying the tetracycline efflux tet (40) gene and the tetracycline ribosomal protection tet (O/W/32/O) gene. The patient was splenectomized. The case was characterized by multi-organ dysfunction and disseminated intravascular coagulopathy, in accordance with the clinical parameters of STSS. More investigations are needed to improve the epidemiology and the pathogenesis of S. suis in human infection. PMID- 27553072 TI - Distribution of CGRP and TRPV2 in Human Paranasal Sinuses. AB - Immunohistochemistry for protein gene product 9.5 (PGP 9.5), calcitonin gene related peptide (CGRP) and the transient receptor potential cation channel subfamily V member 2 (TRPV2) was performed on human paranasal sinuses. It was found that in the paranasal sinuses, mucous membranes contain PGP 9.5 immunoreactive (PGP 9.5-IR) nerve fibers. Such nerve fibers terminated around large blood vessels as fine varicosities. Isolated PGP 9.5-IR nerve fibers were scattered beneath the epithelium. Glandular tissues were also innervated by PGP 9.5-IR nerve fibers. These fibers were numerous in the maxillary and ethmoid sinuses, and relatively rare in the frontal and sphenoid sinuses. CGRP-IR nerve fibers were common in the maxillary sinus whereas TRPV2-IR nerve fibers were abundant in the ethmoid sinus. They were located around large blood vessels in the lamina propria. Many subepithelial nerve fibers contained TRPV2 immunoreactivity in the ethmoid sinus. CGRP- and TRPV2-IR nerve fibers were very infrequent in the frontal and sphenoid sinuses. In the human trigeminal ganglion (TG), sensory neurons contained CGRP or TRPV2 immunoreactivity. CGRP-IR TG neurons were more common than TRPV2-IR TG neurons. CGRP-IR TG neurons were of various cell body sizes, whereas TRPV2-IR TG neurons were mostly medium-to-large. In addition, human spinal and principal trigeminal sensory nuclei contained abundant CGRP- and TRPV2-IR varicosities. This study indicates that CGRP- and TRPV2-containing TG neurons probably innervate the paranasal sinus mucosae, and project into spinal and principal trigeminal sensory nuclei. PMID- 27553073 TI - RSV N-nanorings fused to palivizumab-targeted neutralizing epitope as a nanoparticle RSV vaccine. AB - Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections in children, yet no vaccine is available. The sole licensed preventive treatment against RSV is composed of a monoclonal neutralizing antibody (palivizumab), which targets a conformational epitope located on the fusion protein (F). Palivizumab reduces the burden of bronchiolitis but does not prevent infection. Thus, the development of RSV vaccines remains a priority. We previously evaluated nanorings formed by RSV nucleoprotein (N) as an RSV vaccine, as well as an immunostimulatory carrier for heterologous antigens. Here, we linked the palivizumab-targeted epitope (called FsII) to N, to generate N-FsII nanorings. Intranasal N-FsII immunization elicited anti-F antibodies in mice that were non-neutralizing in vitro. Nevertheless, RSV-challenged animals were better protected against virus replication than mice immunized with N-nanorings, especially in the upper airways. In conclusion, an N-FsII-focused vaccine is an attractive candidate combining N-specific cellular immunity and F-specific antibodies for protection. PMID- 27553074 TI - Orthopedic implant biomaterials with both osteogenic and anti-infection capacities and associated in vivo evaluation methods. AB - Osteogenicity (i.e., properties that promote new bone formation on and around the implant) has long been a clinical requirement for most orthopedic implants. Recently, anti-infection or antibacterial properties have become critical for orthopedic implants (especially without the use of antibiotics). Ideally, orthopedic implant materials with simultaneous anti-infection and osteogenic capacities are extremely promising for orthopedic applications, but such materials are not widely available to date and have only recently been researched. In the first part of this review, numerous attractive material formulations that exhibit both antibacterial and osteogenic capacities as well as surface modification strategies that enhance such capacities are introduced. Several possible mechanisms underlying simultaneous antibacterial and osteogenic properties are also discussed. In the second part of this review, evaluation methods including animal models, analytical tools and available guidelines for assessing antibacterial and osteogenic properties of implantable materials in vivo are summarized and discussed. PMID- 27553075 TI - Neuroglia as targets for drug delivery systems: A review. AB - Targeted drug delivery within the nervous system is an emerging topic of research that involves designing and developing vehicular delivery systems that have the ability to target specific neuronal and non-neuronal cell types in the central and peripheral nervous system. Drugs, genetic material, or any other payloads can be loaded onto such delivery systems and could be used to treat, prevent or manage various neurological disorders. Currently, majority of studies in this field have been concentrated around targeted delivery to neurons. However, the non-neuronal cells within the nervous system, collectively called neuroglia, have been largely ignored, though it is well known that they play a significant role in the pathophysiology of almost all neurological disorders. In this review, we present current developments in the specific area of neuroglia targeted delivery systems and highlight the use of polymeric, metallic, liposomal and other delivery systems used for this purpose. PMID- 27553076 TI - GLP-1 nanomedicine alleviates gut inflammation. AB - The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1beta, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate that GLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). PMID- 27553077 TI - Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo. AB - Therapeutic applications of RNA interference (RNAi) require efficient siRNA delivery strategies in vivo. Combining lipid-based carriers with polymeric nanoparticles offers the favorable properties of both systems. This is the first study to explore polyethylenimine-based lipopolyplexes comprising a low-molecular weight PEI and the phospholipid DPPC for therapeutic siRNA use. Lipopolyplex structures are analyzed by electron microscopy. Biological efficacies are demonstrated in vitro by cellular uptake, knockdown of the target oncogene survivin, and concomitant cell growth inhibition. Upon systemic administration in tumor-bearing mice, here performed by intraperitoneal (i.p.) injection, radioactive biodistribution assays show lipopolyplex-mediated delivery of intact siRNAs. Absence of blood serum parameter alterations, erythrocyte aggregation or immunostimulation, and the observation of animal well-being and stable body weight confirm biocompatibility. Exploring therapeutic efficacies in a preclinical model, a considerable inhibition of prostate carcinoma xenograft growth is achieved, paralleled by an ~65% survivin knockdown in the tumors. We, thus, demonstrate that PEI-based lipopolyplexes represent an efficient platform for therapeutic use of small RNAs. PMID- 27553079 TI - Structure elucidation and NMR assignments of an alkaloid from Ixeris chinensis Nakai. AB - A new alkaloid, 2-amino-1,6-dihydro-pyridine-5-carbaldehyde (1), together with four known compounds, namely 4-hydroxybenzaldehyde (2), 4-hydroxyacetophenone (3), acetophenone-4-O-beta-d-glucoside (4), 2-hydroxyl-6-methoxyacetophenone-4-O beta-d-glucoside (5), were isolated from the CHCl3 extract from Ixeris chinensis Nakai. The structures of 1 was elucidated by spectroscopic methods, including UV, IR, HR-ESI-MS and extensive 1D and 2D NMR techniques. PMID- 27553078 TI - Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men? AB - We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships. The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, beta-blockers, antidepressants, and social support (OR = 1.09, 95 % CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95 % CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important. PMID- 27553080 TI - Determinants of poor self-rated health among adults in urban Mozambique. AB - BACKGROUND: Self-rated health is a measure expressing the general condition of health of individuals. Self-rated health studies are common in developed countries and in some developing regions. Despite increasing proportion of adult and older population in sub-Saharan Africa and poor population health indicators, there is a dearth of studies on self-rated health in the region. This study examines factors associated with poor self-rated health among adult individuals in Maputo metropolitan area in Mozambique. METHODS: Data for this study come from a survey of 1768 individuals aged 18 years or more carried out in Maputo metropolitan area, Mozambique, in 2015. Employing multiple logistic regression, the study used a subsample of 677 female and male respondents aged 40 years or more to estimate the determinants of poor self-rated health. RESULTS: About 54 % of respondents aged 40 years or more believed that their health status was poor. Female respondents [Odds Ratios (OR) = 3.43, p <0.01], single (OR = 4.71, p < 0.05), widow (OR = 1.81, p < 0.05), separated or divorced (OR = 2.08, p < 0.05) and those believing that hypertension or heart problem was a major community health problem (OR = 1.56, p < 0.05) displayed higher odds of reporting poor health than their peers, net of other factors. Furthermore, individuals aged 40 49 years (OR = 0.45, p < 0.01), or 50-59 years (OR = 0.59, p < 0.05), those whose work involves intensive physical activity (OR = 0.60, p < 0.05) and those from households treating drinking water (OR = 0.49, p < 0.01) showed lower odds of reporting poor health, adjusting for other factors. CONCLUSION: Overall, the results point to the importance of age, gender, marital status, socioeconomic circumstances, individuals' health behaviors and perceived community health problems as key determinants of poor self-rated health among adults in Maputo metropolitan area. Given the growing number of adult and older people in sub Saharan Africa, the rising importance of non-communicable diseases and the scarcity of studies on determinants of poor self-rated health among adults in the region, our findings may have implications for a better understanding of the drivers of poor health among adults in urban sub-Saharan Africa. PMID- 27553081 TI - Selecting relevant 3D image features of margin sharpness and texture for lung nodule retrieval. AB - PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the world. Its diagnosis is a challenge task to specialists due to several aspects on the classification of lung nodules. Therefore, it is important to integrate content based image retrieval methods on the lung nodule classification process, since they are capable of retrieving similar cases from databases that were previously diagnosed. However, this mechanism depends on extracting relevant image features in order to obtain high efficiency. The goal of this paper is to perform the selection of 3D image features of margin sharpness and texture that can be relevant on the retrieval of similar cancerous and benign lung nodules. METHODS: A total of 48 3D image attributes were extracted from the nodule volume. Border sharpness features were extracted from perpendicular lines drawn over the lesion boundary. Second-order texture features were extracted from a cooccurrence matrix. Relevant features were selected by a correlation-based method and a statistical significance analysis. Retrieval performance was assessed according to the nodule's potential malignancy on the 10 most similar cases and by the parameters of precision and recall. RESULTS: Statistical significant features reduced retrieval performance. Correlation-based method selected 2 margin sharpness attributes and 6 texture attributes and obtained higher precision compared to all 48 extracted features on similar nodule retrieval. CONCLUSION: Feature space dimensionality reduction of 83 % obtained higher retrieval performance and presented to be a computationaly low cost method of retrieving similar nodules for the diagnosis of lung cancer. PMID- 27553082 TI - Genetic architecture of male floral traits required for hybrid wheat breeding. AB - KEY MESSAGE: This study revealed a complex genetic architecture of male floral traits in wheat, and Rht-D1 was identified as the only major QTL. Genome-wide prediction approaches but also phenotypic recurrent selection appear promising to increase outcrossing ability required for hybrid wheat seed production. Hybrid wheat breeding is a promising approach to increase grain yield and yield stability. However, the identification of lines with favorable male floral characteristics required for hybrid seed production currently poses a severe bottleneck for hybrid wheat breeding. This study therefore aimed to unravel the genetic architecture of floral traits and to assess the potential of genomic approaches to accelerate their improvement. To this end, we employed a panel of 209 diverse winter wheat lines assessed for male floral traits and genotyped with genome-wide markers as well as for Rht-B1 and Rht-D1. We found the highest proportion of explained genotypic variance for the Rht-D1 locus (11-24 %), for which the dwarfing allele Rht-D1b had a negative effect on anther extrusion, visual anther extrusion and pollen mass. The genome-wide scan detected only few QTL with small or medium effects, indicating a complex genetic architecture. Consequently, marker-assisted selection yielded only moderate prediction abilities (0.44-0.63), mainly relying on Rht-D1. Genomic selection based on weighted ridge-regression best linear unbiased prediction achieved higher prediction abilities of up to 0.70 for anther extrusion. In conclusion, recurrent phenotypic selection appears most cost-effective for the initial improvement of floral traits in wheat, while genome-wide prediction approaches may be worthwhile when complete marker profiles are already available in a hybrid wheat breeding program. PMID- 27553083 TI - Nomograms to predict survival after colorectal cancer resection without preoperative therapy. AB - BACKGROUND: The predictive accuracy of the American Joint Committee on Cancer (AJCC) stages of colorectal cancer (CRC) is mediocre. This study aimed to develop postoperative nomograms to predict cancer-specific survival (CSS) and overall survival (OS) after CRC resection without preoperative therapy. METHODS: Eligible patients with stage I to IV CRC (n = 56072) diagnosed from 2004 to 2010 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were allocated into training (n = 27,700), contemporary (n = 3158), and prospective (n = 25,214) validation cohorts. Clinically important variables were incorporated and selected using the Akaike information criterion in multivariate Cox regressions to derive nomograms with the training cohort. The performance of the nomograms was assessed and externally testified using the concordance index (c-index), bootstrap validation, calibration, time-dependent receiver-operating characteristic curves, Kaplan-Meier curves, mosaic plots, and decision curve analysis (DCA). Performance of the conventional AJCC stages was also compared with the nomograms using similar statistics. RESULTS: The nomograms for CSS and OS shared common predictors: sex, age, race, marital status, preoperative carcinoembryonic antigen status, surgical extent, tumor size, location, histology, differentiation, infiltration depth, lymph node count, lymph node ratio, and metastasis. The c-indexes of the nomograms for CSS and OS were 0.816 (95 % CI 0.810-0.822) and 0.777 (95 % CI 0.772-0.782), respectively. Performance evaluations showed that the nomograms achieved considerable predictive accuracy, appreciable reliability, and significant clinical validity with wide practical threshold probabilities, while the results remained reproducible when applied to the validation cohorts. Additionally, model comparisons and DCA proved that the nomograms excelled in stratifying each AJCC stage into three significant prognostic subgroups, allowing for more robust risk classification with an improved net benefit. CONCLUSIONS: We propose two prognostic nomograms that exhibit improved predictive accuracy and net benefit for patients who have undergone CRC resection. The established nomograms are intended for risk assessment and selection of suitable patients who may benefit from adjuvant therapy and intensified follow-up after surgery. Independent external validations may still be required. PMID- 27553084 TI - Evaluation of a novel virtual screening strategy using receptor decoy binding sites. AB - Virtual screening is used in biomedical research to predict the binding affinity of a large set of small organic molecules to protein receptor targets. This report shows the development and evaluation of a novel yet straightforward attempt to improve this ranking in receptor-based molecular docking using a receptor-decoy strategy. This strategy includes defining a decoy binding site on the receptor and adjusting the ranking of the true binding-site virtual screen based on the decoy-site screen. The results show that by docking against a receptor-decoy site with Autodock Vina, improved Receiver Operator Characteristic Enrichment (ROCE) was achieved for 5 out of fifteen receptor targets investigated, when up to 15 % of a decoy site rank list was considered. No improved enrichment was seen for 7 targets, while for 3 targets the ROCE was reduced. The extent to which this strategy can effectively improve ligand prediction is dependent on the target receptor investigated. PMID- 27553085 TI - Outcomes of Osteomyelitis in Patients Hospitalized With Diabetic Foot Infections. AB - BACKGROUND: This study was conducted to evaluate the outcomes of patients with diabetic foot osteomyelitis (DFO) compared to diabetic foot soft tissue infections (STIs). METHODS: 229 patients who were hospitalized with foot infections were retrospectively reviewed, identifying 155 patients with DFO and 74 patients with STI. Primary outcomes evaluated were the rates of amputations and length of hospital stay. DFO was confirmed by the presence of positive bone culture and/or histopathology. RESULTS: Patients with DFO had a 5.6 times higher likelihood of overall amputation (P < .0001), a 3.4 times higher likelihood of major amputation (P = .027) and a 4.2 times higher likelihood of minor amputation (P < .0001) compared to patients without DFO. Major amputation was performed in 16.7% patients diagnosed with DFO and 5.3% of patients diagnosed with STI. Patients with DFO complicated by Charcot neuroarthropathy had a 7 times higher likelihood of undergoing major amputation (odds ratio 6.78, 95% confidence interval 2.70-17.01, P < .0001). The mean hospital stay was 7 days in DFO and 6 days in patients with DFI (P = .0082). Patients with DFO had a higher erythrocyte sedimentation rate (85 vs 71, P = .02) than patients with STI, however the differences in C-reactive protein (13.4 vs 11.8, P = .29) were not significantly different. CONCLUSION: In this study of moderate and severe DFIs, the presence of osteomyelitis resulted in a higher likelihood of amputation and longer hospital stay. Readers should recognize that the findings of this study may not be applicable to less severe cases of DFO that can be effectively managed in an outpatient setting. LEVEL OF EVIDENCE: Level III, retrospective comparative case series. PMID- 27553086 TI - Ammonium-Chloride-Potassium Lysing Buffer Treatment of Fully Differentiated Cells Increases Cell Purity and Resulting Neotissue Functional Properties. AB - Juvenile and fetal, primary, fully differentiated cells are widely considered to be ideal cell types for tissue engineering applications. However, their use in tissue engineering may be hindered through contamination by undesirable cell types. These include blood-associated cells as well as unwanted resident cell types found both in healthy and pathologic donor tissues. Ammonium-chloride potassium (ACK) lysing buffer is used to lyse red blood cells (RBCs) during the isolation of stem cell populations, but has not been explored for the purification of fully differentiated cells. This study sought to investigate the effect of ACK buffer treatment of freshly isolated, fully differentiated cells to increase cell purity and enhance the formation of biofunctional engineered neotissues; this was tested in the well-established cartilage tissue engineering model of the self-assembling process using fetal ovine articular chondrocytes (foACs) and juvenile bovine articular chondrocytes (jbACs). ACK buffer treatment of foACs and jbACs decreased the number of contaminating RBCs by over 60% and additionally reduced the number of apoptotic chondrocytes in the cell isolates. Reducing the number of contaminating RBCs removed cellular detractors to the self assembling process and eliminated an apoptotic stimulus, thus improving neocartilage homogeneity, chondrocyte distribution, and extracellular matrix deposition within the neotissues. For example, in foAC neocartilage, ACK buffer treatment ultimately led to a 170% increase in compressive aggregate modulus, a 130% increase in shear modulus, an 80% increase in tensile modulus, and a 130% increase in ultimate tensile strength of the neocartilage. This work represents the first time that ACK buffer has been used to purify fully differentiated cells and subsequently increase the functional properties of neotissue. PMID- 27553087 TI - Outcome of acute severe ulcerative colitis in patients previously exposed to immunosuppressive therapy. AB - BACKGROUND AND AIM: We aimed to evaluate the outcome of patients with acute severe ulcerative colitis previously exposed to immunosuppressive (IMS) therapy. METHODS: We retrospectively collected data from 86 consecutive patients from 2008. Early outcome was evaluated as response to steroids, rescue therapy, and colectomy rate, whereas colectomy free-survival was determined along the follow up. RESULTS: The overall response rates to steroids and rescue therapy was 33.7% and 90.5%, respectively, while early colectomy rate was 22.1%. Patients previously treated with IMS (n=47) showed a trend towards lower response to steroids (25.5% vs 43.6%; p=0.10), and a high-risk of early colectomy (29.8% vs 12.8%; p=0.07), but a similar response to rescue therapy (87.5% vs 94.4%, p=0.62) when compared with IMS-naive patients (n=39). The overall cumulative probability to avoid the surgery was 67.5% and 56.6% at 12 and 60 months, respectively, regardless of previous exposure to IMS (p=0.30). At multivariate analysis the risk of early colectomy was increased by previous IMS (OR 5.16, p=0.017), anaemia (OR 4.26, p=0.02), and diagnosis above 40 years (OR 5.31, p=0.011). CONCLUSIONS: Patients previously treated with IMS showed a non-significant trend towards a worse response with steroid therapy, a satisfactory response rate to rescue therapy, and a similar probability of avoiding colectomy during the follow-up vs IMS-naive patients. PMID- 27553088 TI - Occupational risk for Crohn's disease: A two-center study. AB - BACKGROUND: Occupational factors have been suggested as possible elements in the etiology of Crohn's disease, although evidences have not been fully obtained. AIMS: This study is to investigate possible associations between occupation and development of Crohn's disease. METHODS: This prospective study was carried out in two major hospitals during January 2010 and December 2014. Demographic and clinical data were collected for the calculation of standard incidence ratios and 95% confidence intervals by occupation. RESULTS: A total of 401 patients with Crohn's disease were recruited into this study. Participants were distributed into 8 major occupational groups, among which "professionists" (17.7%), "service and sales" (18.7%) and "unclassified individuals" (mainly students) (20.2%) took up the most proportions. Increased standard incidence ratios were found in "service and sales" (2.526+/-0.135, 95% CI: 1.939-3.290), "professionists" (4.216+/-0.142, 95% CI: 3.194-5.565), and most significantly, in "administrative staffs" (5.476+/-0.170, 95% CI: 3.926-7.639). In contrast, decreased standard incidence ratios for Crohn's disease were observed in the category of "workers in agriculture, forestry, animal husbandry, fishery and water conservancy" (0.088+/ 0.146, 95% CIs: 0.066-0.117). CONCLUSION: Occupational elements are implicated in the likelihood of development of Crohn's disease. PMID- 27553090 TI - Direct Renin Inhibitor is Better than Angiotensin II Receptor Blocker for Intrarenal Arterioles. AB - BACKGROUND/AIMS: We have reported that the long-term administration of angiotensin II receptor blockers (ARBs) induced unusual proliferative changes of renal afferent arteriolar smooth muscle cells (SMCs) in rats, associated with the overproduction of renin. In this study, we examined that a direct renin inhibitor (DRI: Aliskilen; Novartis Pharma Co, USA) might induce different changes on afferent arteriolar walls compared to ARBs. METHOD: Twenty one 6-weeks-old male spontaneous hypertensive rats (SHRs) were divided into the following three groups: high-dose DRI group (n=7), low-dose DRI group (n=5) and control group (n=9). The rats were fed a standard diet (0.4%NaCl) containing high-dose (150mg/kg/day), low-dose (30mg/kg/day) DRI and without DRI for 12 weeks. The kidneys were examined by histological and immunohistochemical studies. Systolic blood pressure, 24-h urine samples and blood samples were also examined. RESULTS: The afferent arteriolar SMC walls in the two DRI groups showed no proliferative changes. The positive renin expression area was the largest in the high-dose DRI group among the three groups (14.3+/-4.0um2, 6.7+/-2.0um2, 2.6+/ 0.9um2/glomerlus, p=0.020, p=0.008, p=0.017, respectively). CONCLUSION: The long term DRI administration increases tissue and circulatory renin; however, afferent arteriolar proliferative changes as shown in ARBs were not induced. PMID- 27553089 TI - Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas. AB - OBJECTIVES: Aberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of methylation of negative regulators of Wnt signaling: CXXC4, DACT2, HDPR1, and FBXW11 and Shh signaling: HHIP, PTCH1, SUFU, ZIC1, and ZIC4 and correlate it with clinicopathological features in this group of patients. MATERIALS AND METHODS: Methylation-specific PCR was used to detect gene promoter methylation, and real time PCR was used to assess gene expression level. RESULTS: The analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover, ZIC4 methylation correlated with lymph node involvement in oral cancer patients. CONCLUSIONS: Our findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling. CLINICAL RELEVANCE: The methylation of ZIC4 may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of ZIC4, HHIP, and DACT2 in head and neck carcinomas. PMID- 27553091 TI - Enhanced ZnO Thin-Film Transistor Performance Using Bilayer Gate Dielectrics. AB - We report ZnO TFTs using Al2O3/Ta2O5 bilayer gate dielectrics grown by atomic layer deposition. The saturation mobility of single layer Ta2O5 dielectric TFT was 0.1 cm(2) V(-1) s(-1), but increased to 13.3 cm(2) V(-1) s(-1) using Al2O3/Ta2O5 bilayer dielectric with significantly lower leakage current and hysteresis. We show that point defects present in ZnO film, particularly VZn, are the main reason for the poor TFT performance with single layer dielectric, although interfacial roughness scattering effects cannot be ruled out. Our approach combines the high dielectric constant of Ta2O5 and the excellent Al2O3/ZnO interface quality, resulting in improved device performance. PMID- 27553092 TI - A Japanese case of beta-ureidopropionase deficiency with dysmorphic features. AB - beta-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation, and it is caused by a mutation in the UPB1 gene. Approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. Non neurological symptoms have been rarely reported. We describe a case of this disease with developmental delay and dysmorphic features. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant (?+4.5 standard deviation after logarithmic transformation) elevations of beta-ureidopropionic acid and beta-ureidoisobutyric acid, strongly suggesting a diagnosis of beta ureidopropionase deficiency. Subsequent quantitative analysis of pyrimidines by liquid chromatography-tandem mass spectrometry supported this finding. Genetic testing of the UPB1 gene confirmed compound heterozygosity of a novel mutation (c.976C>T) and a previously-reported mutation (c.977G>A) that is common in East Asians. beta-Ureidopropionase deficiency is probably underdiagnosed, considering a wide phenotypical variability, non-specific neurological presentations, and an estimated prevalence of 1/5000-6000. Urine metabolomics should be considered for patients with unexplained neurological symptoms. PMID- 27553093 TI - Modulatory compartments in cortex and local regulation of cholinergic tone. AB - Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states. PMID- 27553094 TI - Effect of Smoking on Infarct Size and Major Adverse Cardiac Events in Patients With Large Anterior ST-Elevation Myocardial Infarction (from the INFUSE-AMI Trial). AB - We sought to investigate the effect of smoking on infarct size (IS) and major adverse cardiac events (MACE) in patients with large anterior ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Participants from the Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction study were categorized according to smoking status (current or previous smoking vs no history of smoking). The primary imaging outcome was cardiac magnetic resonance imaging assessed IS of left ventricular mass (%) at 30 days. The primary clinical outcome was the rate of MACE at 30 days and 1 year, defined as the composite of death, reinfarction, new-onset heart failure, or rehospitalization. Of 447 patients enrolled in Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction, 271 (60.6%) were current or past smokers. Compared with nonsmokers, smokers were almost 10 years younger and had a lower prevalence of clinical co-morbidities. Smokers had better procedural success and angiographic reperfusion compared with nonsmokers. At 30 days, there were no differences between smokers and nonsmokers in median IS (16.8% vs 17.4%, p = 0.67) or metrics of left ventricular function. By multivariable linear regression analysis, smoking was not significantly associated with IS at 30 days (beta coefficient: 0.83, p = 0.42). At 1 year, smokers had lower crude rates of MACE (7.6% vs 15%, p = 0.01). After multivariable adjustment, there were no significant differences in 1-year MACE between smokers and nonsmokers (adjusted hazard ratio 0.73, 95% CI 0.40 to 1.33, p = 0.30). In conclusion, smoking history had no significant effect on IS at 30 days. Although current or previous smokers had lower rates of 1-year MACE than those with no history of smoking, adjustment for baseline characteristics rendered this association nonsignificant. These findings support the hypothesis that the smoker's paradox is largely attributable to differences in demographic and clinical baseline risk, rather than differences in IS after primary percutaneous coronary intervention. PMID- 27553095 TI - Relation of Echocardiographic Characteristics of the Right-Sided Heart With Incident Heart Failure and Mortality in Patients With Sleep-Disordered Breathing and Preserved Left Ventricular Ejection Fraction. AB - Sleep-disordered breathing (SDB) has been associated with right-sided heart dysfunction and adverse cardiovascular outcomes. Longitudinal data are sparse in terms of understanding the prognostic implications of right ventricular remodeling in SDB on cardiovascular risk. We therefore investigated the predictive value of right-sided cardiac functional alterations on incident heart failure (HF) or death in SDB. Patients with SDB who underwent echocardiography within 1 month of index polysomnogram from January 2002 to July 2011 with normal left ventricular ejection fraction were included. Cox proportional prognostic hazard models predicting HF or death were used. Of a potential 375 subjects, 202 fulfilled the inclusion criteria (58 +/- 14 years; 50% men). Subjects were followed for 3.1 +/- 2.4 years with a total of 34 (16.8%) developing HF or death. Right ventricular end-systolic area (hazard ratio [HR] 1.3, 95% CI 1.01 to 1.6, p = 0.038), pulmonary vascular resistance (PVR; HR 1.4, 95% CI 1.1 to 1.7, p = 0.005) and also left atrial volume index (HR 1.7, 95%, CI 1.3 to 2.3, p <0.001) and E/A ratio (HR 1.4, 95% CI 1.1 to 1.7, p <0.001), were predictive of HF or death. Patients with increased PVR had significantly shorter event-free survival than without increased PVR (p = 0.04). In sequential Cox models, a model based on clinical data and left ventricular ejection fraction (chi2, 5.4) was improved by left atrial volume index (chi2, 12.7; p = 0.011) and further increased by PVR (chi2, 19.7; p = 0.015). In conclusion, right-sided heart dysfunction provides important prognostic information in SDB and may aid in identifying those at highest risk to target for closer follow-up. PMID- 27553097 TI - Meta-Analysis of Percutaneous Coronary Intervention With Drug-Eluting Stent Versus Coronary Artery Bypass Grafting for Isolated Proximal Left Anterior Descending Coronary Disease. AB - We performed a meta-analysis of the studies comparing the efficacy and safety of coronary artery bypass surgery against percutaneous coronary intervention with drug-eluting stents (PCI-DES) in patients with isolated LAD disease. Because of the limited randomized trial data, the optimal revascularization strategy for patients with isolated LAD disease remains uncertain. Using MEDLINE and EMBASE to source data, 11 studies (3 randomized trials and 8 cohort studies) including 5,044 participants were identified. No significant difference in mortality between PCI-DES and coronary artery bypass surgery (CABG; 111 of 2,122 [5.2%] and 120 of 2,574 [4.7%]; relative risk [RR] 1.23; 95% confidence interval [CI] 0.90 to 1.69) was detected. For MACE, PCI-DES was associated with significant increase in adverse events (RR 1.41; 95% CI 1.03 to 1.93, 8 studies, 4,230 participants). There were no significant differences in the risk of myocardial infarction (RR 0.86; 95% CI 0.58 to 1.26) or stroke (RR 2.36; 95% CI 0.54 to 10.43) between the 2 groups. There were 239 target vessel revascularization (TVR) events among 2,237 participants in the PCI-DES group (10.7%) and 145 TVR events among 2,793 participants in the CABG group (5.2%) with a significant increased risk of TVR in the PCI group (RR 2.52; 95% CI 1.69 to 3.77, 5,030 participants) compared with CABG. In conclusion, for patients with isolated disease of the LAD, meta-analysis of the available data suggests revascularization with a PCI-DES strategy offers similar mortality, MI, and stroke rates to CABG at the expense of increased TVR. Much of the data are derived from registries using first-generation DES, and further randomized trials with more contemporary platforms are needed. PMID- 27553096 TI - Two-Decade Trends in the Prevalence of Atherosclerotic Risk Factors, Coronary Plaque Morphology, and Outcomes in Adults Aged <=45 Years Undergoing Percutaneous Coronary Intervention. AB - Data are limited about the prevalence trends of risk factors, lesion morphology, and clinical outcomes of coronary artery disease in patients, aged <=45 years, undergoing percutaneous coronary intervention (PCI), between the bare-metal stent (BMS; 1994 to 2002) and drug-eluting stent (DES; 2003 to 2012) eras. From the PCI database at the Cleveland Clinic, we identified 1,640 patients aged <=45 years and without a history of coronary artery bypass grafting who underwent PCI from 1994 to 2012. There were 883 patients in the BMS era cohort with a mean follow-up period of 13.15 years and 757 in the DES era cohort with a mean follow-up of 5.02 years. The DES era had more obese (51.8% vs 44.7%, p <0.001) and diabetes (23.0% vs 19.5%, p = 0.09) patients. DES era patients had more B2/C lesions (74.0% vs 32.5%, p <0.001), more severe preprocedural stenosis (86.1 +/- 12.9 vs 72.2 +/- 21.3, p <0.001), and longer lesions (15.5 +/- 9.9 vs 9.6 +/- 6.8, p <0.001). No difference was observed in the 30-day mortality between the DES and BMS eras. Irrespective of era, diabetics had worse long-term mortality (19.4% vs 9.3%, p <0.001) compared with nondiabetics. Obese patients had similar long-term outcomes compared with nonobese patients. In conclusion, patients aged <=45 years, who underwent a PCI procedure in the DES era had worse risk factor profiles, including obesity, compared with patients in the BMS era. They also had more complex lesions. Procedural and long-term outcomes of these patients have not changed between the 2 eras. Young diabetic patients have worse long-term outcomes compared with nondiabetics. PMID- 27553098 TI - Pattern of Mitral Leaflet Elongation and Its Association With Functional Mitral Regurgitation in Nonischemic Dilated Cardiomyopathy. AB - Adaptive enlargement of the mitral leaflet has been implied to participate in the pathogenesis of functional mitral regurgitation (FMR). The aim of the present study was to observe the elongation pattern of anterior mitral leaflets (AML) and posterior mitral leaflets (PML) in idiopathic dilated cardiomyopathy (DC) and to explore its relation with FMR. Forty normal controls (control group) and 97 patients with idiopathic DC (group DC 0-1+: 36 patients with no or only mild FMR; group DC >1+: 61 patients with more-than-mild FMR) were consecutively recruited. The lengths of AML and PML were measured at the parasternal long-axis view (AML lax, PML-lax) and apical 4-chamber view (AML-4, PML-4) using 2-dimensional echocardiography, as well as tenting height (TH) and mitral annular dimension (MAD). Both AML (AML-lax: 2.4 +/- 0.3 vs 3.0 +/- 0.3 vs 3.1 +/- 0.3 cm; AML-4: 1.9 +/- 0.2 vs 2.5 +/- 0.3 vs 2.6 +/- 0.4 cm) and PML (PML-lax: 1.3 +/- 0.3 vs 2.1 +/- 0.5 vs 2.5 +/- 0.4 cm; PML-4: 1.1 +/- 0.2 vs 1.6 +/- 0.3 vs 1.8 +/- 0.4 cm) were elongated in the DC groups compared to controls (all p <0.001). There was a further elongation of PML in group DC >1+ than in group DC 0-1+ (p <0.05), but the AML length was not different (p >0.05). The ratio of (AML-lax + PML lax)/(TH-lax + MAD-lax) (1.03 +/- 0.10 vs 1.08 +/- 0.09, p <0.05) or AML-lax/(TH lax + MAD-lax) (0.57 +/- 0.06 vs 0.64 +/- 0.08, p <0.001) in group DC >1+ was significantly smaller compared to group DC 0-1+, whereas the ratio of PML-lax/(TH lax + MAD-lax) was similar between the 2 groups (0.46 +/- 0.06 vs 0.44 +/- 0.07, p = 0.138). In conclusion, both the AML and PML were elongated in idiopathic DC, but the extent and pattern were not identical between the 2 leaflets. Inadequate AML elongation proportional to mitral apparatus remodeling more likely contributes to the pathogenesis of FMR. PMID- 27553099 TI - Correlation Between Quantitative Angiography-Derived Translesional Pressure and Fractional Flow Reserve. AB - Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. However, it has the disadvantage of cost and invasive complication risks. We investigated the usefulness of quantitative coronary angiography derived translesional pressure (QCA-TP) for predicting functional myocardial ischemia, using FFR as the gold standard. We retrospectively analyzed 152 coronary narrowings (98 left anterior descending arteries, 28 left circumflex arteries, and 26 right) in 132 patients with mild-severe coronary stenosis who underwent coronary angiography and FFR measurements simultaneously. QCA-TP was calculated using software implemented in the QCA software. Coronary morphology was calculated using both densitometry and lumen edges. Functional myocardial ischemia was defined as an FFR of 0.8 or less. The mean values of diameter stenosis by QCA and FFR were 48.9% +/- 14.9 and 0.76 +/- 0.14, respectively. QCA TP was significantly correlated with FFR (r = 0.76, p <0.01). The cut-off values of QCA-TP for predicting functional myocardial ischemia based on FFR were 72.8 mm Hg for the left anterior descending arteries (accuracy, 86.7%; area under the curve [AUC], 0.93), 60.5 mm Hg for the left circumflex arteries (accuracy, 89.3%; AUC, 0.88), and 64.4 mm Hg for the right (accuracy, 88.5%; AUC, 0.94). Therefore, our data suggest that QCA-TP can predict myocardial ischemia with high diagnostic accuracy. PMID- 27553100 TI - Comparison of the Effects of Incomplete Revascularization on 12-Month Mortality in Patients <80 Compared With >=80 Years Who Underwent Percutaneous Coronary Intervention. AB - Although randomized trial data suggest that complete revascularization improves outcomes after percutaneous coronary intervention (PCI), the impact of differing revascularization strategies in octogenarians is not well defined. We performed a retrospective analysis, which was conducted of 9,628 consecutive patients who underwent PCI at a large UK center. Octogenarians were more likely to have significant co-morbidity, a higher Mehran bleed risk score (24.5 +/- 6.8 vs 13.3 +/- 7.4, p <0.0001), and more complex disease (baseline SYNTAX score 18.7 +/- 11.0 vs 13.1 +/- 8.9, p = 0.002) than younger patients. During PCI, octogenarians were more likely to undergo left main or proximal LAD intervention, but despite this, significantly less likely to receive drug-eluting stents (66.5% vs 80.1%, p <0.001). Postprocedurally, octogenarians had greater residual disease burden (residual SYNTAX score 10.1 +/- 8.7 vs 1.6 +/- 3.3, p <0.0001). At 12 months, adverse outcomes (definite stent thrombosis 3.3% vs 1.1%, p <0.001, clinically driven in-stent restenosis PCI 3.7% vs 2.6%, p = 0.005, and 12-month mortality 12.8% vs 4.2%, p <0.0001) were all more frequent in octogenarians. Although age, shock, diabetes, and BMS use were independently predictive of increased 12-month mortality, incomplete revascularization was not. In conclusion, octogenarians are a complex group to treat balancing high-risk bleeding profile and complex coronary disease. However, in multivariate analysis, incomplete revascularization was not independently predictive of adverse outcomes. These data support a conservative target lesion-only DES-driven revascularization strategy. PMID- 27553101 TI - Prognostic Implications of Left Ventricular Scar Determined by Late Gadolinium Enhanced Cardiac Magnetic Resonance in Patients With Atrial Fibrillation. AB - Left ventricular (LV) scar identified by late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) is associated with adverse outcomes in coronary artery disease and cardiomyopathies. We sought to determine the prognostic significance of LV-LGE in atrial fibrillation (AF). We studied 778 consecutive patients referred for radiofrequency ablation of AF who underwent CMR. Patients with coronary artery disease, previous myocardial infarction, or hypertrophic or dilated cardiomyopathy were excluded. The end points of interest were major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke/transient ischemic attack. Of the 754 patients who met the inclusion criteria, 60% were men with an average age of 64 years. Most (87%) had a normal LV ejection fraction of >=55%. LV-LGE was found in 46 patients (6%). There were 32 MACCE over the mean follow-up period of 55 months. The MACCE rate was higher for patients with LV-LGE (13.0% vs 3.7%; p = 0.002). In multivariate analysis, CHA2DS2-VASc score (hazard ratio [HR] 1.36, 95% CI 1.05 to 1.76), the presence of LV-LGE (HR 3.21, 95% CI 1.31 to 7.88), and the LV-LGE extent (HR 1.43, 95% CI 1.15 to 1.78) were independent predictors of MACCE. In addition, the presence of LV-LGE was an independent predictor for ischemic stroke/transient ischemic attack (HR 3.61, 95% CI 1.18 to 11.01) after adjusting for CHA2DS2-VASc score. In conclusion, the presence and extent of LV scar identified by LGE-CMR were independent predictors of MACCE in patients with AF. PMID- 27553102 TI - Prevalence and Prognostic Implications of Bundle Branch Block in Comatose Survivors of Out-of-Hospital Cardiac Arrest. AB - This study reports the prevalence and prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in the admission electrocardiogram (ECG) of comatose survivors of out-of-hospital cardiac arrest (OHCA). The present study is part of the predefined electrocardiographic substudy of the prospective randomized target temperature management trial, which found no benefit of targeting 33 degrees C over 36 degrees C in terms of outcome. Six hundred eighty-two patients were included in the substudy. An admission ECG, which defined the present study population, was available in 602 patients (88%). These ECGs were stratified by the presence of LBBB, RBBB, or no-BBB (reference) on admission. End points were mortality and neurologic outcome 6 months after OHCA. RBBB was present in 79 patients (13%) and LBBB in 65 patients (11%), and the majority of BBBs (92%) had resolved 4 hours after admission. RBBB was associated with significantly higher 6 months mortality (RBBB: hazard ratio [HR]unadjusted 1.78, 95% confidence interval [CI] 1.30 to 2.43; LBBB: HRunadjusted 1.26, 95% CI 0.87 to 1.81), but this did not reach a level of significance in the adjusted model (HRadjusted 1.33, 95% CI 0.94 to 1.87). Similar findings were seen for neurologic outcome in the unadjusted and adjusted analyses. RBBB was further independently associated with higher odds of unfavorable neurologic outcome (RBBB: adjusted odds ratio 1.97, 95% CI 1.05 to 3.71). In conclusion, BBBs after OHCA were transient in most patients, and RBBB was directly associated with higher mortality and independently associated with higher odds of unfavorable neurologic outcome. RBBB is seemingly an early indicator of an unfavorable prognosis after OHCA. PMID- 27553103 TI - Heart Rate Variability and Sleep-Related Breathing Disorders in the General Population. AB - Obstructive sleep apnea seems to have an important influence on the autonomic nervous system. In this study, we assessed the relations of sleep apnea-related parameters with 24-hour heart rate variability (HRV) in a large population of young and healthy adults. Participants aged 25 to 41 years with a body mass index <35 kg/m(2) and without known obstructive sleep apnea were included in a prospective population-based cohort study. HRV was assessed using 24-hour electrocardiographic monitoring. The SD of all normal RR intervals (SDNN) was used as the main HRV variable. Apnea-Hypopnea Index (AHI) and oxygen desaturation index (ODI) were obtained from nighttime pulse oximetry with nasal airflow measurements. We defined sleep-related breathing disorders as an AHI >=5 or an ODI >=5. Multivariable regression models were constructed to assess the relation of HRV with either AHI or ODI. Median age of the 1,255 participants was 37 years, 47% were men, and 9.6% had an AHI >=5. Linear inverse associations of SDNN across AHI and ODI groups were found (p for trend = 0.006 and 0.0004, respectively). The beta coefficients (95% CI) for the relation between SDNN and elevated AHI were 0.20 (-0.40 to -0.11), p = 0.04 and -0.29 (-0.47 to -0.11), p = 0.002 for elevated ODI. After adjustment for 24-hour heart rate, the same beta coefficients (95% CI) were -0.06 (-0.22 to 0.11), p = 0.51 and -0.14 (-0.30 to 0.01), p = 0.07, respectively. In conclusion, even early stages of sleep-related breathing disorders are inversely associated with HRV in young and healthy adults, suggesting that they are tightly linked with autonomic dysfunction. However, HRV and 24-hour heart rate seem to have common information. PMID- 27553104 TI - Risk Factor Optimization and Guideline-Directed Medical Therapy in US Veterans With Peripheral Arterial and Ischemic Cerebrovascular Disease Compared to Veterans With Coronary Heart Disease. AB - Cardiovascular disease (CVD) is a systemic process involving multiple vascular beds and includes coronary heart disease (CHD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). All these manifestations are associated with an increased risk of subsequent myocardial infarction, stroke, and death. Guideline-directed medical therapy is recommended for all patients with CVD. In a cohort of US veterans, we identified 1,242,015 patients with CVD receiving care in 130 Veterans Affairs facilities from October 1, 2013 to September 30, 2014. CVD included diagnoses of CHD, PAD, or ICVD. We assessed the frequency of risk factor optimization and the use of guideline-directed medical therapy in patients with CHD, PAD alone, ICVD alone, and PAD + ICVD groups. A composite of 4 measures (blood pressure <140/90 mm Hg, A1c <7% in diabetics, statin use, and antiplatelet use in eligible patients), termed optimal medical therapy (OMT) was compared among groups. Multivariate logistic regression was performed with CHD as the referent category. CHD comprised 989,380 (79.7%), PAD alone 70,404 (5.7%), ICVD alone 163,730 (13.2%), and PAD + ICVD 18,501 (1.5%) of the cohort. Overall, only 36% received OMT with adjusted odds ratios of 0.54 (95% CI 0.53 to 0.55), 0.77 (0.76 to 0.78), and 0.97 (0.94 to 1.00) for patients with PAD alone, ICVD alone, and PAD + ICVD, respectively, compared with patients with CHD. In conclusion, OMT was low in all groups. Patients with PAD alone and ICVD alone were less likely to receive OMT than those with CHD and PAD + ICVD. PMID- 27553105 TI - Implementation of a Computerized Order Entry Tool to Reduce the Inappropriate and Unnecessary Use of Cardiac Stress Tests With Imaging in Hospitalized Patients. AB - The rising use of imaging cardiac stress tests has led to potentially unnecessary testing. Interventions designed to reduce inappropriate stress testing have focused on the ambulatory setting. We developed a computerized order entry tool intended to reduce the use of imaging cardiac stress tests and improve appropriate use in hospitalized patients. The tool was evaluated using preimplementation and postimplementation cohorts at a single urban academic teaching hospital. All hospitalized patients referred for testing were included. The co-primary outcomes were the use of imaging stress tests as a percentage of all stress tests and the percentage of inappropriate tests, compared between the 2 cohorts. There were 478 patients in the precohort and 463 in the postcohort. The indication was chest pain in 66% and preoperative in 18% and was not significantly different between groups. The use of nonimaging stress tests increased from 4% in the pregroup to 15% in the postgroup (p <0.001). Among very low-risk chest pain patients, the use of nonimaging stress tests increased from 7% to 25% (p <0.001). Inappropriate testing did not change significantly between groups (12% vs 11%). Inappropriate tests were most often preoperative evaluations (83%). In conclusion, our computerized ordering tool significantly increased the use of nonimaging cardiac stress tests and reduced the use of imaging tests yet was not able to reduce inappropriate use. Our study highlights the differences in cardiac stress testing between hospitalized and ambulatory patients. PMID- 27553106 TI - Reply. PMID- 27553107 TI - The Complex QRS Complex Revisited. PMID- 27553108 TI - Temporal Variability of Global Longitudinal Strain in Stable Patients Undergoing Chemotherapy With Trastuzumab. AB - Global longitudinal strain (GLS) is used to evaluate left ventricular (LV) performance after chemotherapy. Differentiating between reduction in GLS due to clinical change and normal temporal variability in measurement remains a challenge. We quantified interobserver, test-retest variability of GLS by expert observers in relation to variability of GLS quantified for clinical assessment by sonographers in our laboratory. We examined the temporal variability of GLS in 30 patients with normal LV ejection fraction (LVEF >53%) undergoing chemotherapy in the absence of change in medications and clinical symptoms in up to 5 sequential echocardiograms. GLS was quantified using EchoPAC (GE Healthcare, Milwaukee, Wisconsin) and 2-dimensional biplane LVEF was measured from 4- and 2- chamber views. Interobserver test-retest variability of GLS measured in 10 random patients by 2 expert readers was calculated using a one-way analysis of variance. Square root of mean squared error provided the SEM for temporal variability. Baseline LVEF was 59.3 +/- 5.1% and remained relatively unchanged over 12 months, p = 0.87. Temporal variability of GLS measured by sonographers was 1.28% and similar to interobserver test-retest variability of GLS measured by expert observers, 1.12% (p = 0.17). Maximum detectable difference in GLS measured by expert observers was similar to that derived from sequential measurements of GLS (3.2% vs 3.6%, respectively). Temporal variability of GLS among clinically stable patients is 1.28% and similar to interobserver test-retest variability of 1.12% measured by expert observers. In conclusion, a reduction in strain >3.2% during sequential echocardiograms under these conditions may be significant. PMID- 27553109 TI - Outcomes of Combined Endocardial-Epicardial Ablation Compared With Endocardial Ablation Alone in Patients Who Undergo Epicardial Access. AB - Percutaneous epicardial access (EpiAcc) is used in an attempt to improve outcomes of ablation. We aim to report our experience in EpiAcc for management of symptomatic ventricular premature complexes (VPC) and ventricular tachycardia (VT). All patients from January 2004 to July 2014 who underwent EpiAcc as part of a VPC or VT ablation procedure were included. Outcomes between those with endocardial-only (Gp1) and endocardial/epicardial (Gp2) ablation and those for VPC and VT ablation were compared. EpiAcc for VPC or VT ablation was attempted in 173 patients; 10 patients were excluded because of failure of access (n = 7) or no ablation performed (n = 3). Of the remaining 163, 131 patients (80.4%) had undergone previous endocardial ablation. Mean age was 53.7 +/- 15.7 years; 115 (71%) were men. VT ablation was the indication in 105 patients (64%). The underlying substrate was predominately nonischemic cardiomyopathy (49.1%). Epicardial ablation was performed in 115 (70.6%). Procedural and clinical success was obtained in 92.0% and 69.9% of patients, respectively, with no difference between Gp1 and Gp2. Those who underwent VPC ablation had superior clinical outcomes at 1-year follow-up. EpiAcc is feasible in almost all patients with no previous cardiac surgery and permits acute procedural success in >90% of patients, most of whom had failed previous ablation. However, epicardial ablation was not delivered in 1/3 of patients. Epicardial mapping may be helpful as in the absence of an appropriate epicardial site for ablation, and focus can be shifted to more detailed endocardial mapping and ablation. PMID- 27553110 TI - Extracellular fluid management and hypertension in urban dwelling versus rural dwelling hemodialysis patients. AB - BACKGROUND: Rural-dwelling hemodialysis patients have less frequent contact with nephrologists than urban-dwelling patients, and are known to have higher mortality. We hypothesized that rural-dwelling hemodialysis patients would have more evidence of poorly controlled extracellular fluid volume (ECVF) than otherwise similar urban-dwellers. METHODS: We studied prevalent hemodialysis patients within a single renal program in Alberta, Canada and assessed ECFV using bioimpedance spectroscopy (BIS). Our primary outcome was impedance vector length (ohm/m) as assessed by BIS using the Xitron Hydra 4200 device, where shorter vector length indicated poorer ECFV control. Because poor ECFV control can lead to hypertension, we also assessed pre- and post-dialysis blood pressure. We measured outcomes at baseline. RESULTS: We studied 228 hemodialysis patients, of whom 115 (50.4 %) and 113 (49.6 %) were urban- and rural-dwelling, respectively. There were no differences in volume control in urban versus rural participants; odds ratio (OR) for vector length in the lowest sex-specific quartile of vector length was 0.93 (95 % CI 0.54, 1.59) after adjusting for age, sex, diabetic status, years since dialysis initiation and phase angle. The odds of very poor blood pressure control (pre-dialysis blood pressure >=180/100) did not differ between urban and rural participants [fully adjusted OR 0.96 (0.36, 2.60)]. CONCLUSIONS: Differences in ECFV control do not appear to explain higher mortality among remote- and rural- dwelling hemodialysis patients, compared to urban-dwellers. PMID- 27553111 TI - Chylous ascites after colorectal cancer surgery: risk factors and impact on short term and long-term outcomes. AB - PURPOSE: Data on the incidence, risk factors, and oncologic impact of chylous ascites after colorectal cancer surgery are scarce. In this study, we aimed to assess the risk factors and the short-term and long-term impact of chylous ascites after colorectal cancer surgery. METHODS: We retrospectively examined 2917 primary colorectal cancer patients who underwent surgical resection between January 2008 and December 2013. The short-term and long-term outcomes were compared between patients with and those without postoperative chylous ascites, and the risk factors for chylous ascites were analyzed. RESULTS: Chylous ascites developed in 138 (4.7 %) patients. A shorter operative time (odds ratio [OR] 0.992, 95 % confidence interval [CI] 0.988-0.996) and the number of retrieved lymph nodes (OR 1.015, 95 % CI 1.004-1.025) were independent risk factors for postoperative chylous ascites. All patients with chylous ascites were managed conservatively, without surgical intervention. The postoperative hospital stay was similar between the two groups (9.4 vs. 9.2 days, p = 0.467). After a median follow-up of 37 months (range 0-118 months), no significant difference was observed in the 3-year disease-free survival (85.0 vs. 83.9 %, p = 0.408) and 5 year overall survival (93.0 vs. 89.7 %, p = 0.662) between the two groups. CONCLUSIONS: A major drawback of this study was that the definition of chylous ascites was solely based on clinical signs. Nevertheless, we can conclude that chylous ascites after colorectal cancer surgery is associated with a shorter operative time and the number of retrieved lymph nodes, but is not associated with the short-term and long-term outcomes. PMID- 27553113 TI - A Practical Approach to Ketogenic Diet in the Pediatric Intensive Care Unit for Super-Refractory Status Epilepticus. AB - BACKGROUND: Super-refractory status epilepticus (SRSE) ensues when there is no improvement of seizure control in response to anesthetic therapy or seizure recurrence after reduction of anesthetic agents. There is no consensus on standard of care for SRSE. Ketogenic diet (KD) has reported success, but technical challenges exist including inability to feed patients, concomitant steroid use, acidotic states, and lack of dieticians with experience. The optimal protocol for KD is yet to be determined. We describe our approach to initiation of KD in the pediatric intensive care unit (PICU). METHODS: Patients with SRSE who had KD initiation in the PICU were identified. Data from the hospital course were supplemented by review of the electronic medical record. RESULTS: Nine children with SRSE who had KD initiated in the PICU were identified. Descriptive analysis was performed. Mean age was 5.4 years (SD 2.24). Median number of days to start KD from detection of seizures was 13 [interquartile range (IQR) 10-16]. Mean time to achieve ketosis was 4.2 days (SD 3.4). The median number of antiepileptic drugs (AEDs) trialed before KD was started was 4 [IQR 3-4], and the median number of continuous infusions was 2 [IQR 2-3]. After initiation of KD, most patients were weaned off anesthetic infusions by 1 week. Outcomes were variable. CONCLUSIONS: We demonstrated the feasibility of a practical approach to initiation of KD for children with SRSE. These children were successfully weaned off continuous anesthetic infusions. Larger studies are needed to determine effectiveness, safety, and tolerability of KD in the management of SRSE as well as ease of implementation. PMID- 27553112 TI - Robotic pancreatoduodenectomy with vascular resection. AB - PURPOSE: This study aims to define the current status of robotic pancreatoduodenectomy (RPD) with resection and reconstruction of the superior mesenteric/portal vein (RPD-SMV/PV). METHODS: Our experience on RPD, including RPD-SMV/PV, is presented along with a description of the surgical technique and a systematic review of the literature on RPD-SMV/PV. RESULTS: We have performed 116 RPD and 14 RPD-SMV/PV. Seven additional cases of RPD-SMV/PV were identified in the literature. In our experience, RPD and RPD-SMV/PV were similar in all baseline variables, but lower mean body mass and higher prevalence of pancreatic cancer in RPD-SMV/PV. Regarding the type of vein resection, there were one type 2 (7.1 %), five type 3 (35.7 %) and eight type 4 (57.2 %) resections. As compared to RPD, RPD-SMV/PV required longer operative time, had higher median estimated blood loss, and blood transfusions were required more frequently. Incidence and severity of post-operative complications were not increased in RPD-SMV/PV, but post-pancreatectomy hemorrhage occurred more frequently after this procedure. In pancreatic cancer, RPD-SMV/PV was associated with a higher mean number of examined lymph nodes (60.0 +/- 13.9 vs 44.6 +/- 11.0; p = 0.02) and with the same rate of microscopic margin positivity (25.0 % vs 26.1 %). Mean length or resected vein was 23.1 +/- 8.08 mm. Actual tumour infiltration was discovered in ten patients (71.4 %), reaching the adventitia in four patients (40.0 %), the media in two patients (20.0 %), and the intima in four patients (40.0 %). Literature review identified seven additional cases, all reported to have successful outcome. CONCLUSIONS: RPD-SMV/PV is feasible in carefully selected patients. The generalization of these results remains to be demonstrated. PMID- 27553114 TI - [Facial feminization surgery - upper third]. AB - The authors present the upper third of the facial feminization techniques in the context of transgender surgery. These techniques adapted to patients "male to female" are proposed to strong masculine facial features of the patients and for the upper third of the face, based on transfer of adipose tissue, fronto-orbital remodeling and correction of the hairline by scalp advance. PMID- 27553115 TI - A retrospective comparison study of the infra-mammary approach to the standard mastectomy scar in the 2nd stage of tissue expander to implant breast reconstruction. AB - BACKGROUND: Staged expander-to-implant breast reconstruction is plagued by a high prevalence of complications. We have employed an alternative approach of using the infra-mammary crease (IMF) for expander-to-implant exchange. The IMF approach was thought to utilize healthier tissues, which are believed to be less affected by the process of tissue expansion, and reside distant from the field of the radiotherapy boost. METHODS: A retrospective chart review was performed on all patients undergoing a staged implant-based breast reconstruction from 2009 to 2014. Patients were divided into those that received an IMF vs. a mastectomy scar (MS) approach in the second stage of expander-to-implant exchange. Patient characteristics and postoperative complications were extracted. RESULTS: A total of 75 patients undergoing 96-staged reconstructions were included (70 cases MS vs. 26 cases IMF). Patient demographics and implant characteristics were similar between groups. There were no significant differences in overall complications between the groups (11.4% MS vs. 7.7% IMF, P=0.72). All cases of implant exposure occurred in the MS group and had a history of radiation. However, there was no statistical difference in implant exposure between groups (4.3% MS vs. 0% IMF, P=0.56) or in the irradiated patients subgroup (20% MS vs. 0% IMF, P=0.25). CONCLUSIONS: In conclusion, the IMF approach for the second stage of expander-to implant exchange is an alternative technique with a similar prevalence of complications as the traditional mastectomy scar approach. This technique may prove useful in reducing postoperative incisional dehiscence and implant exposure, especially in the context of radiotherapy. PMID- 27553116 TI - [Secondary treatment of cleft lip and palate]. AB - For 18 years our protocol has corrected the cleft lip nose and achieved an intravelar veloplasty at the time of the first operation, leaving the least scaring as possible. No doubt that the best treatment of the sequellae is their prevention: - the oro-nasal fistulas have disappeared; the nostril is almost normal; the continuity of a wide maxillary arch is restored in primary dentition all that favor a nasal ventilation. This context has changed the nature of the secondary treatment described here. When lip and nose are not good enough we must address the residual deformities with the primary surgery principles. The velopharyngeal insufficiency calls for a velar re-repair and the pharyngeal depth is to be reduced by lipofilling. The rare cases of failure are improved by an Orticochea sphincteroplasty. PMID- 27553117 TI - Research Participation Decision-Making Among Youth and Parents of Youth With Chronic Health Conditions. AB - The aims of this qualitative descriptive study were to describe how past experiences with research (including communication, information, values, and support) may contribute to research fatigue among youth and parents of youth with HIV, cystic fibrosis, and Type 1 diabetes. Eighteen parents and youth were purposively recruited from outpatient subspecialty clinics at a major academic medical center. They took part in qualitative interviews and completed a demographics form and the Decisional Conflict Scale. Youth participants also completed the Erikson Psychosocial Stage Inventory. Two major themes emerged: Blurred Lines and Hope for the Future. Research fatigue was not found in this sample. Results point to challenges with informed consent in settings where research and clinical care are integrated and suggest that protective factors allow for continued participation without excess burden on youth and parents. Strategies to minimize research fatigue and support engagement in research are offered. PMID- 27553118 TI - Integrated Pest Management Intervention in Child Care Centers Improves Knowledge, Pest Control, and Practices. AB - INTRODUCTION: To reduce young children's exposure to pests and pesticides, an integrated pest management (IPM) intervention was provided for child care center staff. METHODS: The 7-month IPM education and consultation intervention was conducted by trained nurse child care health consultants in 44 child care centers in California. IPM knowledge surveys were completed by child care staff, objective IPM assessments were completed by research assistants pre- and postintervention, and activity logs were completed by the nurses. RESULTS: There were significant increases in IPM knowledge for the child care staff who attended workshops. There were reductions in the prevalence of pests and increases in IPM practices at the postintervention compared with the preintervention time point. The nurses consulted an average of 5.4 hours per center. DISCUSSION: A nurse-led IPM intervention in child care centers can reduce exposure to harmful substances for young children attending child care centers. PMID- 27553119 TI - Breastfeeding Curricular Content of Family Nurse Practitioner Programs. AB - INTRODUCTION: Health care provider support is essential for breastfeeding success. Family Nurse Practitioners (FNP) are in a unique position to promote and manage breastfeeding. There is a gap in the literature regarding the amount and type of breastfeeding curricular content in FNP programs. METHOD: An online survey of FNP programs was conducted. Data collection included program descriptors, didactic breastfeeding coursework, and clinical breastfeeding opportunities available to students. RESULTS: No programs offered courses specific to breastfeeding: 82% of programs devoted 1 to 2 hours of didactic lactation content. More than three quarters of the programs offered students breastfeeding counseling opportunities; no programs, however, identified specific breastfeeding clinical competencies. DISCUSSION: FNPs can play an integral role in breastfeeding promotion and counseling. There appears to be a lack of education provided to FNPs regarding breastfeeding management. Creative approaches that incorporate lactation education into FNP programs may increase FNPs' breastfeeding knowledge and enhance their ability to provide support to breastfeeding families. PMID- 27553120 TI - Both pre- and post-synaptic alterations contribute to aberrant cholinergic transmission in superior cervical ganglia of APP(-/-) mice. AB - Though amyloid precursor protein (APP) can potentially be cleaved to generate the pathological amyloid beta peptide (Abeta), APP itself plays an important role in regulating neuronal activity. APP deficiency causes functional impairment in cholinergic synaptic transmission and cognitive performance. However, the mechanisms underlying altered cholinergic synaptic transmission in APP knock-out mice (APP(-/-)) are poorly understood. In this study, we conducted in vivo extracellular recording to investigate cholinergic compound action potentials (CAPs) of the superior cervical ganglion (SCG) in APP(-/-) and littermate wild type (WT) mice. Our results demonstrate that APP not only regulates presynaptic activity, but also affects postsynaptic function at cholinergic synapses in SCG. APP deficiency reduces the number of vesicles in presynaptic terminalsand attenuatesthe amplitude of CAPs, likely due to dysfunction of high-affinity choline transporters. Pharmacological and biochemical examination showed that postsynaptic responsesmediated by alpha4beta2 and alpha7 nicotinic acetylcholine receptors are reduced in the absence of APP. Our research provides evidences on how APP regulates cholinergic function and therefore may help to identify potential therapeutic targets to treat cholinergic dysfunction associated with Alzheimer's disease pathogenesis. PMID- 27553122 TI - Oligodendrocytes in health and disease. PMID- 27553121 TI - Emotional arousal state influences the ability of amygdalar endocannabinoid signaling to modulate anxiety. AB - Systemic activation of cannabinoid receptors often induces biphasic effects on emotional memory and anxiety depending on the levels of emotional arousal associated to the experimental context. The basolateral nucleus of the amygdala (BLA) represents a crucial structure for the ability of endocannabinoid (eCB) signaling to modulate emotional behaviour, and receives dense projections from brainstem arousal system nuclei. We examined whether changes in emotional arousal state would influence the ability of acute eCB manipulations within the BLA to modulate anxiety. Rats were tested in an elevated plus maze (EPM) under low or high arousal conditions. The low emotional arousal group was extensively handled and habituated to the experimental room and tested under red light condition, the high emotional arousal group was not handled or habituated and tested under high light condition. We examined amygdalar eCB anandamide (AEA) and 2 arachidonoylglycerol (2-AG) levels immediately after the EPM and the effects of intra-BLA administration of the AEA hydrolysis inhibitor URB597 or the 2-AG hydrolysis inhibitor KML29 on anxiety behaviour. The modulation of anxiety-like behaviour by eCBs in the BLA was strictly dependent on the environmental associated emotional arousal. Pharmacologically-induced elevations of AEA or 2-AG in the BLA decreased anxiety under conditions of low emotional arousal. Conversely, when the level of emotional arousal increased, local eCB manipulation was ineffective in the modulation of the emotional arousal-induced anxiety response. These findings suggest that, depending on the emotional arousal state, eCB system is differentially activated to regulate the anxiety response in the amygdala and help to understand the state-dependency of many interventions on anxiety. PMID- 27553123 TI - Accurate shade image matching by using a smartphone camera. AB - PURPOSE: Dental shade matching by using digital images may be feasible when suitable color features are properly manipulated. Separating the color features into feature spaces facilitates favorable matching. We propose using support vector machines (SVM), which are outstanding classifiers, in shade classification. METHODS: A total of 1300 shade tab images were captured using a smartphone camera with auto-mode settings and no flash. The images were shot at angled distances of 14-20cm from a shade guide at a clinic equipped with light tubes that produced a 4000K color temperature. The Group 1 samples comprised 1040 tab images, for which the shade guide was randomly positioned in the clinic, and the Group 2 samples comprised 260 tab images, for which the shade guide had a fixed position in the clinic. Rectangular content was cropped manually on each shade tab image and further divided into 10*2 blocks. The color features extracted from the blocks were described using a feature vector. The feature vectors in each group underwent SVM training and classification by using the "leave-one-out" strategy. RESULTS: The top one and three accuracies of Group 1 were 0.86 and 0.98, respectively, and those of Group 2 were 0.97 and 1.00, respectively. CONCLUSIONS: This study provides a feasible technique for dental shade classification that uses the camera of a mobile device. The findings reveal that the proposed SVM classification might outperform the shade-matching results of previous studies that have performed similarity measurements of DeltaE levels or used an S, a*, b* feature set. PMID- 27553124 TI - Sensor fault detection and isolation system for a condensation process. AB - This article presents the design of a sensor Fault Detection and Isolation (FDI) system for a condensation process based on a nonlinear model. The condenser is modeled by dynamic and thermodynamic equations. For this work, the dynamic equations are described by three pairs of differential equations which represent the energy balance between the fluids. The thermodynamic equations consist in algebraic heat transfer equations and empirical equations, that allow for the estimation of heat transfer coefficients. The FDI system consists of a bank of two nonlinear high-gain observers, in order to detect, estimate and to isolate the fault in any of both outlet temperature sensors. The main contributions of this work were the experimental validation of the condenser nonlinear model and the FDI system. PMID- 27553125 TI - Characterization of a novel low-temperature-active, alkaline and sucrose-tolerant invertase. AB - A glycoside hydrolase family 32 invertase from Bacillus sp. HJ14 was expressed in Escherichia coli. The purified recombinant enzyme (rInvHJ14) showed typical biochemical properties of low-temperature-active and alkaline enzymes: (i) rInvHJ14 was active and stable in the range of pH 7.0-9.5 with an apparent pH optimum of 8.0; (ii) rInvHJ14 was most active but not stable at 30-32.5 degrees C, with 19.7, 48.2 and 82.1% of its maximum activity when assayed at 0, 10 and 20 degrees C, respectively, and the Ea, DeltaG(*) (30 degrees C), Km (30 degrees C) and kcat (30 degrees C) values for hydrolysis of sucrose by rInvHJ14 was 47.6 kJ mol(-1), 57.6 kJ mol(-1), 62.9 mM and 746.2 s(-1), respectively. The enzyme also showed strong sucrose tolerance. rInvHJ14 preserved approximately 50% of its highest activity in the presence of 2045.0 mM sucrose. Furthermore, potential factors for low-temperature-active and alkaline adaptations of rInvHJ14 were presumed. Compared with more thermostable homologs, rInvHJ14 has a higher frequency of glycine residues and a longer loop but a lower frequency of proline residues (especially in a loop) in the catalytic domain. The catalytic pockets of acid invertases were almost negatively charged while that of alkaline rInvHJ14 was mostly positively charged. PMID- 27553126 TI - Sexual behavior of Pecari tajacu (Cetartiodactyla: Tayassuidae) during periovulatory and early gestation periods. AB - The goal of this study was to describe the sexual behavior in female and male collared peccary. Twenty females and twelve males were monitored in familiar and non-familiar units for two 60 days periods. During both phases, we recorded 2747 sexual interactions initiated by 20 different females toward males and 4461 sexual interactions initiated by 12 males toward females. The frequency of sexual interactions initiated per female significantly increased from proestrus to estrus, and they were significantly more frequently courted. Females initiated olfactory inspections 15.42 times more and were mounted 22.6 times more during estrus than during proestrus. Nulliparous and primiparous females copulated only when exposed to non-parental males. After estrus, the frequency of sexual interactions received by females sharply decreased. One mating event was recorded during the first gestation week and 31 mountings were observed after the second week. In conclusion, the behavioral monitoring is a useful procedure for the recognition of estrus. Our results suggest that ovulation may be associated with the end of the estrus, which will support future work in assisted reproduction in this species. To promote good handling practices, females of reproductive age should be removed from their family unit of origin. PMID- 27553127 TI - Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness. AB - Nitrate-rich beetroot juice (BRJ) increases plasma nitrite concentrations, lowers the oxygen cost (V?O2) of steady-state exercise and improves exercise performance in sedentary and moderately-trained, but rarely in well-trained individuals exercising at sea-level. BRJ supplementation may be more effective in a hypoxic environment, where the reduction of nitrite into nitric oxide (NO) is potentiated, such that well-trained and less well-trained individuals may derive a similar ergogenic effect. We conducted a randomised, counterbalanced, double blind placebo controlled trial to determine the effects of BRJ on treadmill running performance in moderate normobaric hypoxia (equivalent to 2500 m altitude) in participants with a range of aerobic fitness levels. Twelve healthy males (V?O2max ranging from 47.1 to 76.8 ml kg(-1) min(-1)) ingested 138 ml concentrated BRJ (~15.2 mmol nitrate) or a nitrate-deplete placebo (PLA) (~0.2 mmol nitrate). Three hours later, participants completed steady-state moderate intensity running, and a 1500 m time-trial (TT) in a normobaric hypoxic chamber (FIO2 ~ 15%). Plasma nitrite concentration was significantly greater following BRJ versus PLA 1 h post supplementation, and remained higher in BRJ throughout the testing session (p < 0.01). Average V?O2 was significantly lower (BRJ: 18.4 +/- 2.0, PLA: 20.4 +/- 12.6 ml kg(-1) min(-1); p = 0.002), whilst arterial oxygen saturation (SpO2) was significantly greater (BRJ: 88.4 +/- 2.7, PLA: 86.5 +/- 3.3%; p < 0.001) following BRJ. BRJ improved TT performance in all 12 participants by an average of 3.2% (BRJ: 331.1 +/- 45.3 vs. PL: 341.9 +/- 46.1 s; p < 0.001). There was no apparent relationship between aerobic fitness and the improvement in performance following BRJ (r(2) = 0.05, p > 0.05). These findings suggests that a high nitrate dose in the form of a BRJ supplement may improve running performance in individuals with a range of aerobic fitness levels conducting moderate and high-intensity exercise in a normobaric hypoxic environment. PMID- 27553128 TI - Nitric oxide, the new architect of epigenetic landscapes. AB - Nitric oxide (NO) is an endogenously produced signaling molecule with multiple regulatory functions in physiology and disease. The most studied molecular mechanisms underlying the biological functions of NO include its reaction with heme proteins and regulation of protein activity via modification of thiol residues. A significant number of transcriptional responses and phenotypes observed in NO microenvironments, however, still lack mechanistic understanding. Recent studies shed new light on NO signaling by revealing its influence on epigenetic changes within the cell. Epigenetic alterations are important determinants of transcriptional responses and cell phenotypes, which can relay heritable information during cell division. As transcription across the genome is highly sensitive to these upstream epigenetic changes, this mode of NO signaling provides an alternate explanation for NO-mediated gene expression changes and phenotypes. This review will provide an overview of the interplay between NO and epigenetics as well as emphasize the unprecedented importance of these pathways to explain phenotypic effects associated with biological NO synthesis. PMID- 27553129 TI - Central Sensitization in Functional Chronic Pain Syndromes: Overview and Clinical Application. AB - The purpose of this review and clinical application article is to offer nurses up to-date knowledge on peripheral and central sensitization in chronic functional pain syndromes, and to discuss therapies that have shown efficacy in treating various aspects of these disorders. Central sensitization is a result of changes in the peripheral and central nervous system due to noxious stimuli, such as illness or trauma. Once these changes occur, treatment for the associated syndromes requires a multimodal approach that includes behavioral pain psychology, physical therapy, and pharmacological agents that specifically target neuroinflammation, pain modulation, and amplification of pain pathways. More research needs to be conducted on the basis and patient perception of functional pain syndromes to reduce the morbidity and significant disability associated with these illnesses. Nurses have the opportunity to be at the forefront of this research because of their holistic and multidimensional approach to patient care, assessment, and symptom management. PMID- 27553131 TI - Patients' Perception of Chronic-Pain-Related Patient-Provider Communication in Relation to Sociodemographic and Pain-Related Variables: A Cross-Sectional Nationwide Study. AB - Pain is a personal experience and patient-provider communication therefore an essential part of diagnosis and treatment where the patient's perspective needs to be central. The aim of this descriptive cross-sectional study was to investigate chronic-pain-related patient-provider communication in the context of sociodemographic variables, pain variables, perceived outcome of care, and satisfaction with health care providers. A postal questionnaire measuring socio demographic variables, pain characteristics, pain-related health care utilization and patient-provider communication was sent to a sample of 4,500 individuals randomly drawn from the national population of Iceland. A subsample reporting chronic pain and having visited a health care provider for pain the previous six months (n = 401) was analyzed. Relationships between patient-provider communication and other measured variables were tested using bivariate and multivariate statistics. The more chronic pain impaired health-related quality of life, the more provider control the patients perceived in the patient-provider communication. There was also a strong negative relationship between patients' perception of providers' support and openness to discussing symptoms, and satisfaction with health care provider. Patients' perception of their own control in patient-provider communication and involvement in decisions regarding care was related to sociodemographic variables (specifically, education and residence) but not to pain related variables. This study highlights the importance of assessing chronic pain in a broad spectrum, listening, and giving patients time and support to communicate chronic pain and how it affects their life situation. The more interfering the pain is, the more important this is. PMID- 27553130 TI - The Relationship between Pain, Disability, and Sex in African Americans. AB - Older African Americans consistently report diminished capacities to perform activities of daily living (ADL) compared with other racial groups. The extent to which bodily pain is related to declining abilities to perform ADL/ADL disability in African Americans remains unclear, as does whether this relationship exists to the same degree in African American men and women. For nurses to provide optimal care for older African Americans, a better understanding of the relationship between bodily pain and ADL disability and how it may differ by sex is needed. The aim of this study was to examine whether pain, age, education, income, marital status and/or comorbid conditions were associated with ADL disabilities in older African American women and men. This was a cross-sectional descriptive study. The sample included 598 participants (446 women, 152 men) from the first wave of the Baltimore Study on Black Aging. African American women (odds ratio [OR] = 4.06; 95% confidence interval [CI] 2.63-6.26) and African American men (OR = 6.44; 95% CI = 2.84-14.57) who reported bodily pain had greater ADL disability than those who did not report bodily pain. Having two or more comorbid conditions also was significantly associated with ADL disability in African American women (OR = 3.95; 95% CI: 2.09-7.47). Further work is needed to understand pain differences between older African American women and men to develop interventions that can be tailored to meet the individual pain needs of both groups. PMID- 27553132 TI - Evaluation of library preparation methods for Illumina next generation sequencing of small amounts of DNA from foodborne parasites. AB - Illumina library preparation methods for ultra-low input amounts were compared using genomic DNA from two foodborne parasites (Angiostrongylus cantonensis and Cyclospora cayetanensis) as examples. The Ovation Ultralow method resulted in libraries with the highest concentration and produced quality sequencing data, even when the input DNA was in the picogram range. PMID- 27553133 TI - Development of a monoclonal antibody-based colony blot immunoassay for detection of thermotolerant Campylobacter species. AB - Campylobacter species, particularly thermotolerant Campylobacter spp., such as C. jejuni, are major human foodborne pathogens. Culture methods have been routinely used for the detection of this organism in various types of samples. An alternative, simple and rapid confirmation test(s) without further tedious biochemical tests would be useful. Meanwhile, Campylobacter-like colonies can be difficult to identify on agar plates overgrown with competitive bacteria, which can lead to false-negative results. This study was to develop a simple colony blot immunoassay using a new monoclonal antibody (Mab) produced in the present study for rapid screening, confirmation and quantification of campylobacters on culture agar plates. The procedure developed in this study was able to specifically detect thermotolerant Campylobacter spp., but not other non thermotolerant Campylobacter and non-Campylobacter reference strains tested. This assay could detect 105 cells in a single dot. This assay showed 100% correlation with the culture method for the blotted membranes from 21 either chicken meat or vegetable samples experimentally inoculated with thermotolerant campylobacters. Among 101 natural samples of chicken meat (n=44), chicken feces (n=20) and vegetables (n=37), this assay also showed positive for 23 chicken meat and 14 fecal samples that were positive for thermotolerant campylobacters by culture method, and identified four additional suspects that were culture negative. Membranes stored at 4 degrees C for at least 4years could also be used for this assay. The assay developed in this study can be used in quantitative study for immediate or archival usage, and for diagnostic test to preliminarily confirm the presence of thermotolerant Campylobacter on agar plates. PMID- 27553171 TI - ROS in Ca(2+) signaling and disease-part 2. PMID- 27553172 TI - Patient-reported outcomes: nothing without engagement. PMID- 27553174 TI - Biliary tract malignancies: a population-based study on incidence, prognosis and management of patients. AB - BACKGROUND: Biliary tract malignancies are uncommon and few population-based studies are available. METHODS: This nationwide population-based study in Iceland included all patients diagnosed with intra- and extrahepatic cholangiocarcinoma, gallbladder and ampullary cancer from 1984 to 2012. Patients were identified through the Icelandic Cancer Registry. Clinical information was obtained from patient records. RESULTS: Overall 245 patients were identified: 38 had intrahepatic cholangiocarcinoma, 66 extrahepatic cholangiocarcinoma, 73 gallbladder cancer (GBC) and 68 ampullary cancer. Overall incidence for bile tract malignancies was 1-3 per 100,000 person-years and less than 1 by sub-type. The overall bile tract malignancies in males increased from 1.3 (95% CI 0.8-1.8) to 2.5 (1.9-3.1) per 100,000 inhabitants. The incidence of GBC among females decreased from 1.1 (0.7-1.5) to 0.5 (0.2-0.7). Surgery decreased for extrahepatic cholangiocarcinoma (56 to 23%, p = .027), ampullary cancer (80 to 48%, p = .03) and overall bile tract cancer (61 to 32%, p < .0001) but use of chemotherapy increased (4 to 32%, p < .0001). Five-year relative survival rates for men were 15% and 24% for women. No significant improvement was found in survival. CONCLUSIONS: Overall incidence of bile tract malignancies increased in males and GBC decreased in women. Long-term survival is poor and did not improve despite changes in treatment. PMID- 27553173 TI - Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs. AB - Zika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2). Productive ZIKV replication (?2 log increase in viral load, ZIKV nonstructural protein-1 (NS1) protein expression and cytopathic effects (CPE)) was found in the placental (JEG-3), neuronal (SF268), muscle (RD), retinal (ARPE19), pulmonary (Hep-2 and HFL), colonic (Caco-2),and hepatic (Huh-7) cell lines. These findings helped to explain the trans-placental transmission and other clinical manifestations of ZIKV. Notably, the prostatic (LNCaP), testicular (833KE) and renal (HEK) cell lines showed increased ZIKV load and/or NS1 protein expression without inducing CPE, suggesting their potential roles in sexual transmission with persistent viral replication at these anatomical sites. Comparatively, none of the placental and genital tract cell lines allowed efficient DENV-2 replication. Among the nonhuman cell lines, nonhuman primate (Vero and LLC-MK2), pig (PK-15), rabbit (RK-13), hamster (BHK21) and chicken (DF 1) cell lines supported productive ZIKV replication. These animal species may be important reservoirs and/or potential animal models for ZIKV. The findings in our study help to explain the viral shedding pattern, transmission and pathogenesis of the rapidly disseminating ZIKV, and are useful for optimizing laboratory diagnostics and studies on the pathogenesis and counter-measures of ZIKV. PMID- 27553175 TI - Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. AB - Controversial results on the predictive value of programmed death ligand 1 (PD L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape. PMID- 27553176 TI - Nest predation risk influences a cavity-nesting passerine during the post hatching care period. AB - Some nest predators visually assess parental activities to locate a prey nest, whereas parents modify fitness-related traits to reduce the probability of nest predation, and/or nestlings fledge early to escape the risky nest environment. Here, we experimentally tested if the parental and fledging behaviours of oriental tits (Parus minor) that bred in the nest-box varied with cavity conditions associated with nest predation risk during the nestling period. The entrance of experimental nest-boxes was enlarged to create a long-term risk soon after clutch competition. A short-term risk, using simulated playbacks with a coexisting control bird and avian nest predator sound, was simultaneously applied to the nest-boxes whether or not the long-term risk existed. We found that the parents reduced their hourly feeding trips, and the nestlings fledged early with the long-term risk, although the nest mortality of the two nest-box types was low and did not differ. While this study presents a portion of prey-predator interactions with the associated uncertainties, our results highlight that the entrance size of cavities for small hole-nesting birds may play an important role in determining their fitness-related traits depending upon the degree of perceived risk of nest predation. PMID- 27553178 TI - Impact of lens thickness on complications of hypermature cataract surgery: A prospective study. AB - PURPOSE: To assess the correlation between lens thickness (LT) measured by ultrasonography and duration of surgery as well as complications. SETTING: The study was conducted in a hospital in the Parisian suburb of Bobigny, France. DESIGN: A prospective and monocentric study was conducted. All patients undergoing surgery for hypermature cataract between January 2013 and March 2014 were included. METHODS: Morphological features, including LT, axial length, anterior chamber depth and vitreous length were assessed using A-scan ultrasonography. The other parameters assessed were the duration of surgery, occurrence of complications during surgery, visual acuity (VA) and corneal edema score one week after surgery. RESULTS: Thirty eyes of 29 patients were included. Mean LT was 4.11+/-0.64mm (median: 3.89mm). Mean surgery duration was 24.2+/ 8.7min. Three patients experienced complications during surgery: 2 capsular breaks and 1 posterior lens dislocation. At one week, the mean decimal VA was 0.49+/-0.34 and the mean corneal edema score was 0.76+/-1.09. The Pearson correlation coefficient was r=0.27 (P>0.05) between LT and surgery duration while it was r=-0.53 (P=0.01) between VA and LT. No correlation was found for the other parameters studied. DISCUSSION: In this study, the linear correlation between LT and the surgery duration was low. The visual recovery at day 7 appeared inversely correlated with the LT. CONCLUSIONS: LT did not seem to be a marker for longer surgery duration but appeared related to the visual recovery at one week. PMID- 27553179 TI - [Unusual progression of an epimacular membrane: Case report]. PMID- 27553177 TI - Human heme oxygenase 1 is a potential host cell factor against dengue virus replication. AB - Dengue virus (DENV) infection and replication induces oxidative stress, which further contributes to the progression and pathogenesis of the DENV infection. Modulation of host antioxidant molecules may be a useful strategy for interfering with DENV replication. In this study, we showed that induction or exogenous overexpression of heme oxygenase-1 (HO-1), an antioxidant enzyme, effectively inhibited DENV replication in DENV-infected Huh-7 cells. This antiviral effect of HO-1 was attenuated by its inhibitor tin protoporphyrin (SnPP), suggesting that HO-1 was an important cellular factor against DENV replication. Biliverdin but not carbon monoxide and ferrous ions, which are products of the HO-1 on heme, mediated the HO-1-induced anti-DENV effect by non-competitively inhibiting DENV protease, with an inhibition constant (Ki) of 8.55 +/- 0.38 MUM. Moreover, HO-1 induction or its exogenous overexpression, rescued DENV-suppressed antiviral interferon response. Moreover, we showed that HO-1 induction by cobalt protoporphyrin (CoPP) and andrographolide, a natural product, as evidenced by a significant delay in the onset of disease and mortality, and virus load in the infected mice's brains. These findings clearly revealed that a drug or therapy that induced the HO-1 signal pathway was a promising strategy for treating DENV infection. PMID- 27553180 TI - Traumatic subconjunctival dislocation of lens. PMID- 27553181 TI - Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome. AB - OBJECTIVE: To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome. METHODS: In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP). RESULTS: Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased continuously over 120 weeks. Mean increases in the modified per protocol population was 9.2 % for FVC, 8.8 % for FEV1, and 6.1 % for MVV after 120 weeks. All patients <=14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater (P < 0.05) in treated patients. CONCLUSIONS: Long-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients (<=14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved. PMID- 27553182 TI - Systolic time intervals derived from electrocardiographic gated intra-renal artery Doppler waveform associated with left ventricular systolic function. AB - The aims of this study were to investigate the correlation between renal and cardiac STIs, including pre-ejection period (PEP), ejection time (ET), and PEP/ET, and to assess the diagnostic values of renal STIs in predicting left ventricular ejection fraction (LVEF) <50%. The cross sectional observation study enrolled 230 participants. The renal STIs, including renal PEP (rPEP), renal ET (rET), and rPEP/rET, were measured from electrocardiographic gated renal Doppler ultrasound and cardiac PEP, ET, and PEP/ET were measured from echocardiography. Renal STIs were correlated with cardiac STIs (all P < 0.001). Multivariate analyses showed that rPEP/rET was independently associated with LVEF (unstandardized coefficient beta = -0.116, P = 0.046) and LVEF <50% (odds ratio = 2.145, per 0.11 increase; P = 0.017). The areas under the curve for rPEP, 1/rET, and rPEP/rET in predicting LVEF <50% were 0.773, 0.764, and 0.821, respectively. The sensitivity and specificity of rPEP/rET > 0.46 in prediction of LVEF <50% were 76.7% and 78.1%, respectively. Our study demonstrated that the novel parameters of renal STIs were significantly associated with cardiac STIs. However, the clinical application of renal STIs needs to be investigated in future studies. PMID- 27553183 TI - Laparoscopic Burch Colposuspension Using a 3-Trocar System: Tips and Tricks. AB - STUDY OBJECTIVE: To describe a technique for performing laparoscopic Burch colposuspension using a 3-trocar system. DESIGN: This educational video provides step-by-step instructions for performing a laparoscopic Burch colposuspension. This study was exempt from institutional review board approval. SETTING: Midurethral slings are an effective surgical treatment for women with stress urinary incontinence, but not all patients are candidates for, or desire, vaginal mesh. For stress incontinence, nonmesh surgical procedures include pubovaginal fascial slings and retropubic Burch colposuspension. Colposuspension may be performed via an open or laparoscopic approach. As with other minimally invasive surgeries, laparoscopic colposuspension has decreased blood loss, pain, and length of stay with equivalent outcomes at 2 years compared with open procedures. This video describes a technique for performing laparoscopic Burch colposuspension using a 3-trocar system. INTERVENTIONS: A laparoscopic Burch colposuspension is described using a 3-trocar system. Detailed step-by-step instructions are given, along with visualization of pertinent anatomy. Supplies needed for this procedure include a 0-degree, 5-mm laparoscope; two 5-mm trocars, 1 to be placed in the umbilicus and 1 in the left lower quadrant; one 5/12-mm trocar to be placed in the right lower quadrant for passing needles; a closed knot pusher; laparoscopic scissors; and 2 needle drivers. This technique assumes that the primary surgeon (located on the patient's left) is right-handed and that both surgeons can suture and tie knots laparoscopically. Tips are highlighted to ensure safety and ensure successful completion of the procedure. CONCLUSION: Laparoscopic Burch colposuspension offers a nonmesh-based repair for women with stress urinary incontinence using a minimally invasive approach. It is a reasonable alternative to offer patients with stress urinary incontinence who do not desire repair using vaginal mesh. PMID- 27553184 TI - Fertility Outcomes After Ablation Using Plasma Energy Versus Cystectomy in Infertile Women With Ovarian Endometrioma: A Multicentric Comparative Study. AB - STUDY OBJECTIVE: To compare the probability of postoperative pregnancy in infertile women with ovarian endometrioma larger than 3 cm in diameter, managed by either ablation using plasma energy or cystectomy. DESIGN: A multicentric case control study (Canadian Task Force classification II-2). SETTING: Six surgical departments, affiliated with 4 university hospitals and 2 private facilities. PATIENTS: One hundred four infertile patients with ovarian endometrioma larger than 3 cm. INTERVENTIONS: Endometrioma ablation using plasma energy was performed in 64 patients (61.5%) and cystectomy in 40 patients (38.5%). MEASUREMENTS AND MAIN RESULTS: Patients were enrolled in the CIRENDO prospective cohort database (NCT02294825) from June 2009 to June 2014 and managed in 6 different facilities. The minimum length of follow-up was 1 year. Postoperative probabilities of pregnancy in patietns and control subjects were estimated using the Kaplan-Meier method with 95% confidence intervals (CIs) and compared using the log-rank test. The Cox model was used to assess independent predictive factors for pregnancy. Patients managed by plasma energy were significantly older than patients managed by cystectomy, had significantly higher overall revised American Fertility Society (rAFS) score, and had higher rate of Douglas pouch obliteration, deep endometriosis, and colorectal localizations. After a mean follow-up of 35.3 +/- 17.5 months (range, 12-60), fertility outcomes were comparable between the groups. The probability of pregnancy at 24 and 36 months after surgery in plasma energy and cystectomy groups was, respectively, 61.3% (95% CI, 48.2%-74.4%) versus 69.3% (95% CI, 54.5%-83%) and 84.4% (95% CI, 72%-93.4%) versus 78.3% (95% CI, 63.8%-90%). The Cox's model revealed that the type of surgical procedure on ovarian endometrioma had no statistically significant impact on the probability of pregnancy, after adjustment for women's age, bilateral cysts larger than 3 cm, colorectal endometriosis, and rAFS stage of endometriosis. CONCLUSION: Postoperative pregnancy rates were comparable after management of ovarian endometrioma by either ablation using plasma energy or cystectomy despite an overall higher rate of unfavorable fertility predictive factors in women managed by ablation. PMID- 27553185 TI - History of Uterine Surgery Is Not Associated With an Increased Severity of Bladder Deep Endometriosis. AB - STUDY OBJECTIVE: To analyze whether a history of uterine surgery correlates with disease severity in patients with bladder deep infiltrating endometriosis (DIE). DESIGN: This was an observational, cross-sectional study using data collected prospectively (Canadian Task Force classification II-2). SETTING: A single university tertiary referral center. PATIENTS: We included all nonpregnant women younger than age 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed during a face-to-face interview that was conducted by the surgeon in the month preceding the surgery. INTERVENTIONS: One hundred seven women with histologically proven bladder DIE were enrolled in this study. For the purpose of the study, the women were assigned to 2 groups before surgery: a study group that included women with a history of a scarred uterus (SU) (SU+, n = 16) and a control group that included women without SU (SU-, n = 99). Both groups were compared in terms of their general characteristics, medical histories, surgical findings, and the severity of the disease. MEASUREMENTS AND MAIN RESULTS: Patient age and body mass index were higher for the SU+ group as compared to the SU- group (37.9 +/- 5.6 vs 32.2 +/- 4.7, p < .01, and 24.7 +/- 4.9 vs 21.9 +/- 2.9, p = .03, respectively). Preoperative painful symptom scores did not differ between the 2 groups. No significant difference was observed in the rates of history for surgery for endometriosis (n = 11 [68.7%] vs n = 49 [53.8], p = .27). Comparison of the anatomic distribution of the lesions did not reveal a significant difference. The total American Society for Reproductive Medicine score did not differ between the groups (32.0 +/- 34.4 vs 35.5 +/- 34.5, p = .71). The incidence rate of isolated bladder DIE did not differ between the 2 study groups (n = 6 [37.5%] vs n = 40 [43.9%], p = .79). CONCLUSION: SU before surgery for endometriosis was observed in 14.9% of cases of bladder DIE; however, this was not related to an increased severity of the disease. This observational study hence does not appear to support the pathophysiologic hypothesis of a transmyometrial source for bladder DIE. PMID- 27553186 TI - Uterine Artery Embolization Versus Methotrexate for Cesarean Scar Pregnancy in a Chinese Population: A Meta-analysis. AB - This systematic review and meta-analysis was performed to compare the efficacy and safety of uterine artery embolization (UAE) followed by curettage and methotrexate (MTX) plus curettage in the treatment of cesarean scar pregnancy (CSP) in China. Studies published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System), and China National Knowledge Information were systematically searched. The main outcome measures included the time for serum beta-human chorionic gonadotropin (beta-hCG) normalization, the duration of hospital stay, blood losses, and adverse events. Results were expressed as the weighted mean difference (WMD) or risk ratio with 95% confidence intervals (CIs). Results showed that 11 studies involving a total of 725 patients were included in this meta-analysis. Compared with MTX plus curettage, UAE followed by curettage had 16.76 days less time for beta-hCG normalization (WMD = 16.76 days; 95% CI, -24.60 to -8.92; p < .001), and 15.05 days less of hospital stay (WMD = -15.05 days; 95% CI, -25.42 to -4.67; p = .004). CSP patients who underwent UAE had 343.24 mL less blood loss compared with those treated with MTX plus curettage (WMD = -343.24 mL; 95% CI, -432.95 to -253.54; p < .001). Moreover, UAE was associated with a lower incidence of adverse events than those treated with MTX plus curettage (relative risk = 0.46; 95% CI, 0.26-0.81; p = .008). In conclusion, UAE combined with curettage significantly shortened the time for beta-hCG normalization and hospital stay and reduced blood losses and adverse events compared with the administration of MTX plus curettage. For patients with CSP, UAE followed by curettage appears to be more advantageous and may be a priority option. Further well-conducted, large-scale trials are needed to validate these findings. PMID- 27553187 TI - Editorial (Thematic Issue: Medical Applications of Enzymes). PMID- 27553188 TI - Targeting of calcitonin gene-related peptide action as a new strategy for migraine treatment. AB - Migraine is a chronic, recurrent disorder, characterized by attacks of severe pain, affecting around 1% of adult population. Many studies suggest, that trigeminovascular system plays a key role in pathogenesis of migraine and other primary headaches. Calcitonin gene-related peptide (CGRP) is an endogenous substance, which is regarded a key mediator released from trigeminovascular system after stimulation of sensory nerve endings, responsible for dilatation of peripheral vessels and sensory transmission. CGRP is and extensively studied peptide as one of the most promising targets in migraine drug research. In the article we focus on the role of CGRP in the pathophysiology of migraine and present current data on CGRP antagonists and CGRP monoclonal antibodies. PMID- 27553189 TI - Cerebral vasomotor reactivity in neurodegenerative diseases. AB - Small-caliber cerebral vessels change their diameters in response to alterations of key metabolite concentrations such as carbon dioxide or oxygen. This phenomenon, termed the cerebral vasomotor reactivity (CVMR), is the basis for blood flow regulation in the brain in accordance with its metabolic status. Typically, CVMR is determined as the amount of change in cerebral blood flow in response to a vasodilating stimulus, which can be measured by various neuroimaging methods or by transcranial Doppler. It has been shown that CVMR is impaired in cerebrovascular diseases, but there is also evidence of a similar dysfunction in neurodegenerative disorders. Here, we review studies that have investigated CVMR in the common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. Moreover, we discuss potential neurodegenerative mechanisms responsible for the impairment of CVMR. PMID- 27553190 TI - Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages. AB - Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1 to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage. PMID- 27553191 TI - Oestradiol synthesized by female neurons generates sex differences in neuritogenesis. AB - Testosterone produced by the foetal testis is converted by male neurons to oestradiol, which masculinizes neuronal morphology. Female neurons are known to synthesize oestradiol in absence of exogenous testosterone. However, the role of neuronal oestradiol on the differentiation of foetal female neurons is unknown. Here we show that, due to endogenous neuronal oestradiol synthesis, female hippocampal neurons have higher expression of the neuritogenic protein Neurogenin 3 and enhanced neuritogenesis than males. Exogenous application of testosterone or its metabolite dihydrotestosterone increases Neurogenin 3 expression and promotes neuritogenesis in males, but reduces these parameters in females. Together our data indicate that gonadal-independent oestradiol synthesis by female neurons participates in the generation of sex differences in hippocampal neuronal development. PMID- 27553192 TI - An assessment of the central disposition of intranasally administered insulin lispro in the cerebrospinal fluid of healthy volunteers and beagle dogs. AB - Intranasally administered regular insulin and insulin aspart have shown cognitive benefit for patients with Alzheimer's disease (AD). To support development of intranasally administered insulin analogs for AD, the central disposition of intranasal insulin lispro in the cerebrospinal fluid (CSF) of healthy volunteers was investigated. Healthy volunteers (N = 8) received two sequential doses of intranasal insulin lispro (48 or 80 IU followed by 160 IU) by Aero Pump in an open-label, single-period study with serial CSF and serum sampling over 5 hours after each dose. CSF insulin lispro was also measured in beagle dogs (N = 6/dose group) that received either 24 IU/kg (equivalent local nasal (IU/cm2) dose to the human 160 IU dose) or 192 IU/kg intranasally, using the same device. Insulin lispro was measured in the CSF and serum using a validated enzyme-linked immunosorbent assay method, and pharmacokinetic parameters were calculated by standard noncompartmental methods. Intranasal administration of insulin lispro was well tolerated. Insulin lispro concentrations in the CSF of humans at all dose levels were below the limit of quantification. Serum insulin lispro concentrations were quantifiable only up to 1-2 hours in the majority of subjects. In contrast to insulin lispro in the CSF of humans, insulin lispro was detectable in the CSF at both dose levels in dogs, and serum concentrations of insulin lispro were generally higher in dogs than in healthy volunteers. The absence of insulin lispro in CSF from healthy volunteers and the lack of robust exposure-response analyses will hinder the development of intranasally administered insulin lispro for AD. PMID- 27553194 TI - Sonochemical synthesis and characterization of Co3O4 nanocrystals in the presence of the ionic liquid [EMIM][BF4]. AB - For the first time, a sonochemical process has been used to synthesis cobalt oxide Co3O4 nanoflowers and nanorods morphology in the presence of the ionic liquid 1-Ethyl-3-methylimidazolium tetrafluoroborate [EMIM][BF4] as reaction media and morphology template. Different sonication time periods and different molar ratios of the ionic liquid (IL) were used to investigate their effects on the structural, optical, chemical and magnetic properties of the produced Co3O4 nanoparticles. During synthesis process brown powder contains cobalt hydroxide Co(OH)2 and cobalt oxyhydroxide (Cobalt hydroxide oxide) CoO(OH) was formed, after calcination in air for 4h at 400 degrees C a black powder of Co3O4 nanoparticles was produced. The produced Co3O4 nanoparticles properties were characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), transmission electron microscopy (TEM), FTIR spectroscopy, UV-vis spectroscopy, and Vibrating Sample Magnetometer (VSM). To explain the formation mechanism of Co3O4 NPs some investigations were carried on the brown powder before calcination. PMID- 27553193 TI - Clinical action measures improve the reliability of feedback on quality of care in diabetes centres: a retrospective cohort study. AB - BACKGROUND: Assessment of quality of care using classical threshold measures (TM) is open to debate. Measures that take into account the clinician's actions and the longitudinal nature of chronic care are more reliable, although their major limitation is that they require more sophisticated electronic health records. We created a clinical action measure (CAM) for the control of LDL and non-HDL cholesterol from low-complexity data, and investigated how quality of care in individual diabetes centres based on the CAM is related to that based on the classical TM. METHODS: Data was used from 3421 diabetes patients treated in 95 centres, collected in two consecutive retrospective data collections. Patients met the TM when their index value was below target. Patients met the CAM when their index value was below target or above target but for whom treatment initiation or intensification, or possible contraindication, was indicated. RESULTS: Based on the TM, 60-70 % of the patients received good care. This percentage increased significantly using the CAM (+5 %, p < 0.001). At the centre level, the CAM was associated with a higher median score, and a change in position among centres ('poor', 'good' or 'excellent' performer) for 5-10 % of the centres. CONCLUSIONS: Judging quality of diabetes care of a centre based on a TM may be misleading. Low-complexity data available from a quality improvement initiative can be used to construct a more fair and feasible measure of quality of care. PMID- 27553195 TI - Mechanistic investigations in sono-hybrid (ultrasound/Fe2+/UVC) techniques of persulfate activation for degradation of Azorubine. AB - Persulfate-based oxidation of recalcitrant pollutants has been investigated as an alternative to OH radical based advanced oxidation processes due to distinct merits such as greater stability and non-selective persistent reactivity of SO4- oxidant species. The present study has attempted to highlight mechanistic features of persulfate-based decolorization of textile dye (Azorubine) using sono hybrid techniques of activation. Three activation techniques, viz. sonolysis, Fe2+ ions and UVC light and combinations thereof, have been examined. UVC is revealed to be the most efficient decolorization technique. The mechanism of sonolysis (i.e. thermal activation of persulfate in the bubble-bulk interfacial region) is revealed to be almost independent of the mechanism of UVC. Fe2+ activation is revealed to have an adverse interaction with UVC due to scavenging of sulfate radicals by Fe2+ ions. The best hybrid activation technique for persulfate-based degradation and mineralization of Azorubine is UVC+ultrasound. Due to independent mechanisms, degradation and mineralization of the dye obtained with simultaneous application of UVC and ultrasound is nearly equal to the sum of degradation and mineralization obtained using individual techniques. PMID- 27553197 TI - Penetrating Thoracic Trauma Patients with Gross Physiological Derangement: A Responsibility for the General Surgeon in the Absence of Trauma or Cardiothoracic Surgeon? AB - BACKGROUND: Penetrating trauma is becoming increasingly common in parts of the world where previously it was rare. At the same time, general surgeons and surgical trainees are becoming more specialized, and less comfortable operating within areas beyond their zone of specialization. OBJECTIVE: The purpose of this manuscript is to assess the technical difficulties encountered in operating on patients who have sustained penetrating trauma, and to prove to general surgeons that the technical skills and techniques required are no different to those required for abdominal surgery, and do not require additional dexterity. METHODS: This prospective study was conducted in an Academic Trauma unit over a 3-year period. All patients who were operated upon for penetrating thoracic trauma were included in the study. The pre-operative management, techniques of surgical repair and the outcome were assessed. RESULTS: One hundred and forty-five patients were included in the study over a 3-year period. There were 97 patients with stab wounds, 47 with gunshot wounds and 1 patient with an injury from an angle grinder. Mortality was six times greater in those patients with gunshot wounds, than those with stab wounds. Several patients had multiple thoracic organ injuries. There were 57 patients who were operated upon for thoracic vessel injury. There was a 3.5 % mortality overall. Eighty-eight patients sustained pulmonary injury with a 7 % mortality, and they were managed mainly by simply repair, tractotomy or stapled partial non-anatomical lobectomy. Of the 39 patients with cardiac trauma, there was 17 % mortality, and all cases were managed by simple repair. There were 5 patients with an oesophageal injury of whom 3 died (mortality of 60 %). Twenty-four patients had thoraco-abdominal injuries with 30 % mortality. CONCLUSION: Most of the injuries in the chest can be managed by simple procedures to control life-threatening bleeding. The techniques required are similar to those taught to and are practiced comfortably by general surgeons used to work in the abdominal cavity. We encourage the general surgeon who receives a grossly unstable patient with penetrating thoracic trauma to operate, instead of adding risk to the patient's physiology by a transfer to cardio-thoracic or dedicated trauma units. PMID- 27553196 TI - Identification of a stable major-effect QTL (Parth 2.1) controlling parthenocarpy in cucumber and associated candidate gene analysis via whole genome re sequencing. AB - BACKGROUND: Parthenocarpy is an important trait for yield and quality in many plants. But due to its complex interactions with genetic and physiological factors, it has not been adequately understood and applied to breeding and production. Finding novel and effective quantitative trait loci (QTLs) is a critical step towards understanding its genetic mechanism. Cucumber (Cucumis sativus L.) is a typical parthenocarpic plant but the QTLs controlling parthenocarpy in cucumber were not mapped on chromosomes, and the linked markers were neither user-friendly nor confirmed by previous studies. Hence, we conducted a two-season QTL study of parthenocarpy based on the cucumber genome with 145 F2:3 families derived from a cross between EC1 (a parthenocarpic inbred line) and 8419 s-1 (a non-parthenocarpic inbred line) in order to map novel QTLs. Whole genome re-sequencing was also performed both to develop effective linked markers and to predict candidate genes. RESULTS: A genetic linkage map, employing 133 Simple Sequence Repeats (SSR) markers and nine Insertion/Deletion (InDel) markers spanning 808.1 cM on seven chromosomes, was constructed from an F2 population. Seven novel QTLs were identified on chromosomes 1, 2, 3, 5 and 7. Parthenocarpy 2.1 (Parth2.1), a QTL on chromosome 2, was a major-effect QTL with a logarithm of odds (LOD) score of 9.0 and phenotypic variance explained (PVE) of 17.0 % in the spring season and with a LOD score of 6.2 and PVE of 10.2 % in the fall season. We confirmed this QTL using a residual heterozygous line97-5 (RHL97-5). Effectiveness of linked markers of the Parth2.1 was validated in F3:4 population and in 21 inbred lines. Within this region, there were 57 genes with nonsynonymous SNPs/InDels in the coding sequence. Based on further combined analysis with transcriptome data between two parents, CsARF19, CsWD40, CsEIN1, CsPPR, CsHEXO3, CsMDL, CsDJC77 and CsSMAX1 were predicted as potential candidate genes controlling parthenocarpy. CONCLUSIONS: A major-effect QTL Parth2.1 and six minor-effect QTLs mainly contribute to the genetic architecture of parthenocarpy in cucumber. SSR16226 and Indel-T-39 can be used in marker-assisted selection (MAS) of cucumber breeding. Whole genome re-sequencing enhances the efficiency of polymorphic marker development and prediction of candidate genes. PMID- 27553198 TI - Outcome of Laparoscopic Treatment of Anorectal Malformations in Children. AB - BACKGROUND: Operative correction of anorectal malformations (ARMs) remains a challenge in pediatric surgery. The study aimed to evaluate the outcomes of laparoscopic treatment of ARM in children. METHODS: From 2007 to 2014, we performed 104 laparoscopic-assisted anorectal pull-through procedures in children with a mean age of 11.3 +/- 0.4 months and ARMs. Clinical assessment, surgical durations, complications, and postoperative outcome were investigated. RESULTS: The mean duration of the operation was 126.5 +/- 17.2 min. Mean intraoperative bleeding was 20 +/- 5.7 g. Three (2.9 %) children required conversion to laparotomy. One (0.9 %) child developed a pelvic abscess, requiring an additional intervention. Three to six months after laparoscopic-assisted anorectal pull through, 72 patients were hospitalized for stoma closure. Good functional results were achieved in 39 (54.2 %) patients. On examination of the perineum, 11 (15.3 %) patients were found to have mucosal prolapse. The circular symmetric anal reflex to tactile stimulation was confirmed in 53 (73.6 %) patients and a tactile weakened anal reflex in 5 (6.9 %) children. At the 1-year follow-up, constipation was present in nine (12.5 %) patients and soling in two (2.8 %) patients. A barium enema study performed after the operation showed good outcomes in 67 (93.1 %) patients and fair outcomes in 5 (6.9 %) patients. None had a poor outcome. CONCLUSIONS: Our experience confirms that laparoscopic-assisted anorectal pull through enabled complete correction of ARM in the meanwhile avoiding damage to the rectum and anus. Also, the technique of double bipolar myostimulation of muscle complex in laparoscopic ARM might lead to these better results. PMID- 27553199 TI - International Association for Trauma Surgery and Intensive Care (IATSIC) Presidential Address: Improving Trauma Care Globally: How is IATSIC Doing? AB - ABSTARCT: IATSIC is the foremost professional society addressing trauma care globally. How is it doing in meeting the needs of most injured patients? The vast majority (65 %) of trauma deaths occur in the poorer half of the world (low income and lower-middle-income countries), where injury rates are the highest. IATSIC has accomplished a tremendous amount and has much to be proud of. However, most of its work thus far has been concentrated in the wealthier half of the world (upper-middle-income and high-income countries). For example, most of the speakers on IATSIC's biannual program are from upper-middle-income and high income countries and most of IATSIC's courses are conducted in these countries. IATSIC's trauma systems publications have been utilized in countries at all economic levels (including many low-income and lower middle-income countries), but much more needs to be done. IATSIC'S foundation is its membership. Only 5 % of our members come from the poorer half of the world. In order to make more of a difference for the majority of injured people in the world, IATSIC needs to expand its reach to where they live. Major priorities are: (1) increase representation from low- and lower middle-income countries in our scientific program; (2) disseminate of our courses more widely; (3) increase utilization of our trauma system publications, especially for higher yield activities, such as longitudinal monitoring of trauma systems, implementation in health policy, and developing curricula for trauma care in medical schools and in post-graduate training; and (4) especially, recruit new members from low- and lower-middle income countries. PMID- 27553200 TI - Viral proteins expressed in the protozoan parasite Eimeria tenella are detected by the chicken immune system. AB - BACKGROUND: Eimeria species are parasitic protozoa that cause coccidiosis, an intestinal disease commonly characterised by malabsorption, diarrhoea and haemorrhage that is particularly important in chickens. Vaccination against chicken coccidiosis is effective using wild-type or attenuated live parasite lines. The development of protocols to express foreign proteins in Eimeria species has opened up the possibility of using Eimeria live vaccines to deliver heterologous antigens and function as multivalent vaccine vectors that could protect chickens against a range of pathogens. RESULTS: In this study, genetic complementation was used to express immunoprotective virus antigens in Eimeria tenella. Infectious bursal disease virus (IBDV) causes Gumboro, an immunosuppressive disease that affects productivity and can interfere with the efficacy of poultry vaccination programmes. Infectious laryngotracheitis virus (ILTV) causes a highly transmissible respiratory disease for which strong cellular immunity and antibody responses are required for effective vaccination. Genes encoding the VP2 protein from a very virulent strain of IBDV (vvVP2) and glycoprotein I from ILTV (gI) were cloned downstream of 5'Et-Actin or 5'Et-TIF promoter regions in plasmids that also contained a mCitrine fluorescent reporter cassette under control of the 5'Et-MIC1 promoter. The plasmids were introduced by nucleofection into E. tenella sporozoites, which were then used to infect chickens. Progeny oocysts were sorted by FACS and passaged several times in vivo until the proportion of fluorescent parasites in each transgenic population reached ~20 % and the number of transgene copies per parasite genome decreased to < 10. All populations were found to transcribe and express the transgene and induced the generation of low titre, transgene-specific antibodies when used to immunise chickens. CONCLUSIONS: E. tenella can express antigens of other poultry pathogens that are successfully recognised by the chicken immune system. Nonetheless, further work has to be done in order to improve the levels of expression for its future use as a multivalent vaccine vector. PMID- 27553201 TI - A new piperidine alkaloid from the leaves of Microcos paniculata L. AB - A new piperidine alkaloid, microcosamine C (1), and one known compound, microcosamine A (2) were isolated from the leaves of Microcos paniculata. Structure elucidation was carried out using HR-ESI-MS, 1D and 2D NMR spectroscopic methods and by comparison with data reported in the literature. The absolute configuration at the C-3 hydroxy group of 1 was established by a Mosher esterification procedure. Both the isolates (1-2) were evaluated for cytotoxicity against four selected tumour cell lines and showed only weak activity against RAW 264.7 cell line. PMID- 27553203 TI - Helional induces Ca2+ decrease and serotonin secretion of QGP-1 cells via a PKG mediated pathway. AB - The secretion, motility and transport by intestinal tissues are regulated among others by specialized neuroendocrine cells, the so-called enterochromaffin (EC) cells. These cells detect different luminal stimuli, such as mechanical stimuli, fatty acids, glucose and distinct chemosensory substances. The EC cells react to the changes in their environment through the release of transmitter molecules, most importantly serotonin, to mediate the corresponding physiological response. However, little is known about the molecular targets of the chemical stimuli delivered from consumed food, spices and cosmetics within EC cells. In this study, we evaluated the expression of the olfactory receptor (OR) 2J3 in the human pancreatic EC cell line QGP-1 at the mRNA and protein levels. Using ratiofluorometric Ca(2+) imaging experiments, we demonstrated that the OR2J3 specific agonist helional induces a transient dose-dependent decrease in the intracellular Ca(2+) levels. This Ca(2+) decrease is mediated by protein kinase G (PKG) on the basis that the specific pharmacological inhibition of PKG with Rp-8 pCPT-cGMPS abolished the helional-induced Ca(2+) response. Furthermore, stimulation of QGP-1 cells with helional caused a dose-dependent release of serotonin that was comparable with the release induced by the application of a direct PKG activator (8-bromo-cGMP). Taken together, our results demonstrate that luminal odorants can be detected by specific ORs in QGP-1 cells and thus cause the directed release of serotonin and a PKG-dependent decrease in intracellular Ca(2.) PMID- 27553204 TI - Very Long-Term Follow-Up After Coronary Rotational Atherectomy: A Single-Center Experience. AB - We assessed the very long-term follow-up of a large cohort of unselected patients treated with coronary rotational atherectomy (RA). All 143 patients who underwent RA at our institution from 2000 to 2013 and with complete baseline and follow-up information were analyzed in a retrospective manner. Major adverse cardiac events (MACE) were defined as the composite of target vessel revascularization (TVR), acute myocardial infarction, and all-cause mortality. The mean follow-up was 8.2 years. The 10-year cumulative incidence of MACE for all patients was 57.9% (standard error [SE]: 5.0%). When comparing patients who received a drug-eluting stent (DES; n = 68) versus patients who did not (balloon only, bare-metal stent, or none of the aforementioned; n = 75), the RA + DES demonstrated very long-term MACE of 49.2% (SE: 7.5%) versus 62.7% (SE: 6.1%), P = .160 with TVR as the most discriminating factor, 10.7% (SE: 4.0%) versus 29.2% (SE: 6.0%), P = .016. Our results point to RA having reasonable long-term clinical results, especially in combined treatment with DES. To date, our study has the longest follow-up after RA. PMID- 27553202 TI - Getting to the heart of intracellular glucocorticoid regeneration: 11beta-HSD1 in the myocardium. AB - Corticosteroids influence the development and function of the heart and its response to injury and pressure overload via actions on glucocorticoid (GR) and mineralocorticoid (MR) receptors. Systemic corticosteroid concentration depends largely on the activity of the hypothalamic-pituitary-adrenal (HPA) axis, but glucocorticoid can also be regenerated from intrinsically inert metabolites by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), selectively increasing glucocorticoid levels within cells and tissues. Extensive studies have revealed the roles for glucocorticoid regeneration by 11beta-HSD1 in liver, adipose, brain and other tissues, but until recently, there has been little focus on the heart. This article reviews the evidence for glucocorticoid metabolism by 11beta-HSD1 in the heart and for a role of 11beta-HSD1 activity in determining the myocardial growth and physiological function. We also consider the potential of 11beta-HSD1 as a therapeutic target to enhance repair after myocardial infarction and to prevent the development of cardiac remodelling and heart failure. PMID- 27553205 TI - Low-Volume Polyethylene Glycol with Ascorbic Acid for Colonoscopy Preparation in Elderly Patients: A Randomized Multicenter Study. AB - BACKGROUND: Minimal data exist regarding the use of low-volume purgatives for elderly (>=65 years) patients. We aimed to investigate the bowel-cleansing efficacy and patient tolerability of split-dose 2 liters (L)-polyethylene glycol with ascorbic acid (2L-PEGA) in elderly outpatients undergoing colonoscopy. METHODS: Patients who underwent morning colonoscopies were randomly assigned to one of 3 arms: single-dose 4L-PEG on the day before colonoscopy; split-dose 4L PEG; or split-dose 2L-PEGA. The quality of bowel preparation was assessed using the Boston Bowel Preparation Scale (BBPS). RESULTS: Of 230 patients enrolled, 198 were analyzed. The proportion of adequate bowel preparations in split-dose 2L PEGA was higher than that in single-dose 4L-PEG (92.1 vs. 75.0%, p = 0.009) and similar to split-dose 4L-PEG. The mean BBPS scores for global and right colon preparation in the split-dose 2L-PEGA were comparable to split-dose 4L-PEG but higher than those in the single-dose 4L-PEG. The proportion of patients who ingested the entire volume of solution in 2L-PEGA was higher than that in single dose 4L-PEG (96.8 vs. 80.9%, p = 0.011). Patients receiving 2L-PEGA expressed more willingness to repeat the same preparation than other groups. The rate of adverse events did not differ among the 3 groups. CONCLUSIONS: Split-dose 2L-PEGA was an effective, safe, and comfortable method for colonoscopy preparation in elderly outpatients. PMID- 27553206 TI - Nursing Skill Mix, Nurse Staffing Level, and Physical Restraint Use in US Hospitals: a Longitudinal Study. AB - BACKGROUND: Although it is plausible that nurse staffing is associated with use of physical restraints in hospitals, this has not been well established. This may be due to limitations in previous cross-sectional analyses lacking adequate control for unmeasured differences in patient-level variables among nursing units. OBJECTIVE: To conduct a longitudinal study, with units serving as their own control, examining whether nurse staffing relative to a unit's long-term average is associated with restraint use. DESIGN: We analyzed 17 quarters of longitudinal data using mixed logistic regression, modeling quarterly odds of unit restraint use as a function of quarterly staffing relative to the unit's average staffing across study quarters. SUBJECTS: 3101 medical, surgical, and medical-surgical units in US hospitals participating in the National Database of Nursing Quality Indicators during 2006-2010. Units had to report at least one quarter with restraint use and one quarter without. MAIN MEASURES: We studied two nurse staffing variables: staffing level (total nursing hours per patient day) and nursing skill mix (proportion of nursing hours provided by RNs). Outcomes were any use of restraint, regardless of reason, and use of restraint for fall prevention. KEY RESULTS: Nursing skill mix was inversely correlated with restraint use for fall prevention and for any reason. Compared to average quarters, odds of fall prevention restraint and of any restraint were respectively 16 % (95 % CI: 3-29 %) and 18 % (95 % CI: 8-29 %) higher for quarters with very low skill mix. CONCLUSIONS: In this longitudinal study there was a strong negative correlation between nursing skill mix and physical restraint use. Ensuring that skill mix is consistently adequate should reduce use of restraint. PMID- 27553207 TI - Gambling Disorder and Affect Regulation: The Role of Alexithymia and Attachment Style. AB - The aim of the present study was to explore the dimensions of alexithymia and attachment styles in a group of disordered gamblers and to evaluate the relationship between alexithymia, attachment styles, and the severity of gambling disorder. Sixty disordered gamblers diagnosed according to the diagnostic and statistical manual-5 filled out the Kurzfragebogen zum Glucksspielverhalten, the 20-Item Toronto Alexithymia Scale, and the Experiences in Close Relationships Revised. Approximately 70 % of the sample displayed 'intermediate' and 'severe' gambling severity levels on the Kurzfragebogen zum Glucksspielverhalten, and 77 % showed 'high' or 'borderline' levels of alexithymia on the Toronto Alexithymia Scale (mean = 56.40). Regarding attachment styles, 70 % of the sample displayed an 'insecure' attachment, with a particularly high prevalence of the 'fearful' style (26.66 %). A linear regression analysis revealed that only the anxiety dimension of the Experiences in Close Relationships questionnaire predicted the severity of gambling. Our data appear to confirm that gambling disorder is characterised by emotional and relational dysregulation, and that pathological gambling behaviours may serve as external regulators of internal undifferentiated emotional states. PMID- 27553208 TI - Determinants of Change in the Cost-effectiveness Threshold. AB - The cost-effectiveness threshold in health care systems with a constrained budget should be determined by the cost-effectiveness of displacing health care services to fund new interventions. Using comparative statics, we review some potential determinants of the threshold, including the budget for health care, the demand for existing health care interventions, the technical efficiency of existing interventions, and the development of new health technologies. We consider the anticipated direction of impact that would affect the threshold following a change in each of these determinants. Where the health care system is technically efficient, an increase in the health care budget unambiguously raises the threshold, whereas an increase in the demand for existing, non-marginal health interventions unambiguously lowers the threshold. Improvements in the technical efficiency of existing interventions may raise or lower the threshold, depending on the cause of the improvement in efficiency, whether the intervention is already funded, and, if so, whether it is marginal. New technologies may also raise or lower the threshold, depending on whether the new technology is a substitute for an existing technology and, again, whether the existing technology is marginal. Our analysis permits health economists and decision makers to assess if and in what direction the threshold may change over time. This matters, as threshold changes impact the cost-effectiveness of interventions that require decisions now but have costs and effects that fall in future periods. PMID- 27553210 TI - Ballot on industrial action by GPs averted as government accepts BMA's demands. PMID- 27553209 TI - The Impact of Diabetes-Related Complications on Preference-Based Measures of Health-Related Quality of Life in Adults with Type I Diabetes. AB - INTRODUCTION: This study estimates health-related quality of life (HRQoL) or utility decrements associated with type 1 diabetes mellitus (T1DM) using data from a UK research program on the Dose Adjustment For Normal Eating (DAFNE) education program. METHODS: A wide range of data was collected from 2341 individuals who undertook a DAFNE course in 2009-2012, at baseline and for 2 subsequent years. We use fixed- and random-effects linear models to generate utility estimates for T1DM using different instruments: EQ-5D, SF-6D, and EQ-VAS. We show models with and without controls for HbA1c and depression, which may be endogenous (if, for example, there is reverse causality in operation). RESULTS: We find strong evidence of an unobserved individual effect, suggesting the superiority of the fixed-effects model. Depression shows the greatest decrement across all the models in the preferred fixed-effects model. The fixed-effects EQ 5D model also finds a significant decrement from retinopathy, body mass index, and HbA1c (%). Estimating a decrement using the fixed-effects model is not possible for some conditions where there are few new cases. In the random-effects model, diabetic foot disease shows substantial utility decrements, yet these are not significant in the fixed-effects models. CONCLUSION: Utility decrements have been calculated for a wide variety of health states in T1DM that can be used in economic analyses. However, despite the large data set, the low incidence of several complications leads to uncertainty in calculating the utility weights. Depression and diabetic foot disease result in a substantial loss in HRQoL for patients with T1DM. HbA1c (%) appears to have an independent negative impact on HRQoL, although concerns remain regarding the potential endogeneity of this variable. PMID- 27553211 TI - The transcriptional regulator TBX3 promotes progression from non-invasive to invasive breast cancer. AB - BACKGROUND: TBX3 is a T-box transcription factor repressor that is elevated in metastatic breast cancer and is believed to promote malignancy of tumor cells, possibly by promoting cell survival and epithelial-mesenchymal transition. METHODS: The relative expression of TBX3 was assessed in the 21T cell lines which were derived from an individual patient and represent three distinct stages of breast cancer progression: 21PT, atypical ductal hyperplasia; 21NT, ductal carcinoma in situ; and 21MT-1, invasive mammary carcinoma. Two different isoforms of TBX3 (TBX3iso1 and TBX3iso2) were overexpressed to evaluate cell survival/colony forming ability, growth, and invasion in the ductal carcinoma in situ-like 21NT cell line using an in vitro Matrigel model of cancer progression. In addition, TBX3 expression was knocked down to evaluate the effects of downregulating TBX3 on the invasive mammary carcinoma-like 21MT-1 cell line. Finally, PCR array profiling was used to assess alterations in gene expression due to TBX3 overexpression in the 21NT cells. RESULTS: TBX3 is abundant in the invasive 21MT-1 cell line, while being minimally expressed in the non-invasive 21NT and 21PT cell lines. Overexpression of either TBX3iso1 or TBX3iso2 in 21NT cells resulted in increased cell survival/colony forming ability, growth vs. apoptosis and invasion in Matrigel. In contrast, short hairpin RNA-mediated knockdown of TBX3 in the 21MT-1 cells resulted in smaller colonies, with a more regular, less dispersed (less infiltrative) morphology. Array profiling of the 21NT TBX3 iso1 and iso2 transfectants showed that there are common alterations in expression of several genes involved in signal transduction, cell cycle control/cell survival, epithelial-mesenchymal transition and invasiveness. CONCLUSIONS: Overall, these results indicate that TBX3 (isoform 1 or 2) expression can promote progression in a model of early breast cancer by altering cell properties involved in cell survival/colony formation and invasiveness, as well as key regulatory and EMT/invasiveness-related gene expressions. PMID- 27553212 TI - Clinical efficacy of alpha4 integrin block with natalizumab in ankylosing spondylitis. PMID- 27553213 TI - Novel algorithms for the pragmatic use of ultrasound in the management of patients with rheumatoid arthritis: from diagnosis to remission. AB - The absence of specific guidance on how to use ultrasound (US) to diagnose and manage patients with inflammatory arthritis, especially with rheumatoid arthritis (RA) has hindered the optimal utilisation of US in clinical practice, potentially limiting its benefits for patient outcomes. In view of this, a group of musculoskeletal US experts formed a working group to consider how this unmet need could be satisfied and to produce guidance (additional to European League against Rheumatism (EULAR) imaging recommendations) to support clinicians in their daily clinical work. This paper describes this process and its outcome, namely five novel algorithms, which identify when US could be used. They are designed to aid diagnosis, to inform assessment of treatment response/disease monitoring and to evaluate stable disease state or remission in patients with suspected or established RA, by providing a pragmatic template for using US at certain time points of the RA management. A research agenda has also been defined for answering unmet clinical needs. PMID- 27553215 TI - Response to: 'Denosumab, cortical bone and bone erosion in rheumatoid arthritis' by Rossini et al. PMID- 27553214 TI - Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. AB - OBJECTIVE: To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA). METHODS: Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24. RESULTS: Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p<=0.001; non responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p<=0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p<=0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05). CONCLUSIONS: In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo. TRIAL REGISTRATION NUMBER: NCT01695239; EudraCT2011-002326-49; Results. PMID- 27553216 TI - Levels and Profiles of Polybrominated Diphenyl Ethers in Breast Milk During Different Nursing Durations. AB - Eight PBDE congeners, BDE-28, 47, 99, 100, 153, 154, 183 and 209, were measured using gas chromatography coupled to mass spectrometry. The concentrations of Sigma8PBDEs ranged from 0.04 to 19.93 ng g(-1) lipid weight (lw), with median and mean value of 1.21 and 2.72 ng g(-1) lw. PBDE congeners were detected in approximately 90 % of samples with BDE-209 as the dominant one. No significant correlations were found between the mothers' age, body mass index and PBDEs concentrations. We estimated the infant's dietary intake of the studied PBDEs via human milk during different nursing durations, and found that babies younger than 1 month might take a relatively higher body burden of PBDEs. The median levels of Sigma8PBDEs were 0.74, 2.80, 2.43 and 0.90 ng g(-1) lw in colostrum, milk sampled at 1, 3 and 6 months after birth, respectively. High consumption of animal-origin food after birth may lead to the elevated SigmaPBDEs concentrations in breast milk. A rational nutrition deployment is essential for postpartum mother. PMID- 27553217 TI - Metformin improved health-related quality of life in ethnic Chinese women with polycystic ovary syndrome. AB - BACKGROUND: Few studies have assessed whether the amelioration of the clinical signs of polycystic ovary syndrome (PCOS) achieved by treatment leads to improvement in the health-related quality of life (HRQoL) of patients. This study was aimed to examine the HRQoL of ethnic Chinese women with PCOS who received metformin treatment. METHODS: This prospective study was conducted at a medical center in Taiwan. Study participants aged 18-45 years were diagnosed as having PCOS according to the Rotterdam criteria, and all received metformin treatment. Their HRQoL was assessed using generic (WHOQOL-Bref) and PCOS-specific (Chi PCOSQ) instruments. Mixed effect models were used to examine the effects of metformin on repeatedly measured HRQoL. Additional analyses using stratified patients characteristics (overweight vs. normal; hyperandrogenism vs. non hyperandrogenism) were done. RESULTS: We recruited 109 participants (56 % were overweight, 80 % had hyperandrogenism). Among the domain scores of WHOQOL-Bref, the psychological domain score was the lowest one (12.64 +/- 2.2, range 4-20). Weight (3.25 +/- 1.59, range 1-7) and infertility (3.38 +/- 1.93, range 1-7) domain scores were relatively low among the domain scores of Chi-PCOSQ. Overweight and hyperandrogenic patients had significantly lower HRQoL as compared with those of normal weight and non-hyperandrogenic patients, respectively. Metformin significantly improved the physical domain of WHOQOL-Bref (p = 0.01), and the infertility (p = 0.043) and acne and hair loss aspects (p = 0.008) of PCOS-specific HRQoL. In the subgroup analysis, significantly improved HRQoL following metformin treatment appeared for only overweight and hyperandrogenism subgroups. CONCLUSIONS: Metformin might improve health-related quality of life of polycystic ovary syndrome women by ameliorating psychological disturbances due to acne, hair loss and infertility problems, especially for overweight and hyperandrogenic patients. PMID- 27553218 TI - Decision-making in social contexts in youth with ADHD. AB - This study examined reward-related decision-making in children and adolescents with ADHD in a social context, using economic games. We furthermore examined the role of individual differences in reward-related decision-making, specifically, the roles of reward sensitivity and prosocial skills. Children and adolescents (9 17 years) with ADHD-combined subtype (n = 29; 20 boys) and healthy controls (n = 38; 20 boys) completed the ultimatum game and dictator game as measures of reward related decision-making in social contexts. Prosocial skills were measured with the Interpersonal Reactivity Index. The ADHD group had a larger discrepancy between ultimatum game and dictator game offers than controls, indicating strategic rather than fairness driven decisions. This finding was supported by self-reports showing fewer individuals with ADHD than controls who considered fairness as motive for the decisions. Perspective taking or empathic concern did not differ between groups and was not significantly associated with offers. In conclusion, the results suggest that rather than a failure to understand the perspective of others, children and adolescents with ADHD were less motivated by fairness than controls in simple social situations. Results encourage the use of economic games in ADHD research. PMID- 27553219 TI - Racial and Ethnic Disparities in ADHD Diagnosis and Treatment. AB - OBJECTIVES: We examined racial/ethnic disparities in attention deficit/hyperactivity disorder (ADHD) diagnosis and medication use and determined whether medication disparities were more likely due to underdiagnosis or undertreatment of African-American and Latino children, or overdiagnosis or overtreatment of white children. METHODS: We used a population-based, multisite sample of 4297 children and parents surveyed over 3 waves (fifth, seventh, and 10th grades). Multivariate logistic regression examined disparities in parent reported ADHD diagnosis and medication use in the following analyses: (1) using the total sample; (2) limited to children with an ADHD diagnosis or symptoms; and (3) limited to children without a diagnosis or symptoms. RESULTS: Across all waves, African-American and Latino children, compared with white children, had lower odds of having an ADHD diagnosis and of taking ADHD medication, controlling for sociodemographics, ADHD symptoms, and other potential comorbid mental health symptoms. Among children with an ADHD diagnosis or symptoms, African-American children had lower odds of medication use at fifth, seventh, and 10th grades, and Latino children had lower odds at fifth and 10th grades. Among children who had neither ADHD symptoms nor ADHD diagnosis by fifth grade (and thus would not likely meet ADHD diagnostic criteria at any age), medication use did not vary by race/ethnicity in adjusted analysis. CONCLUSIONS: Racial/ethnic disparities in parent-reported medication use for ADHD are robust, persisting from fifth grade to 10th grade. These findings suggest that disparities may be more likely related to underdiagnosis and undertreatment of African-American and Latino children as opposed to overdiagnosis or overtreatment of white children. PMID- 27553220 TI - Risk Stratification to Decrease Unnecessary Diagnostic Imaging for Acute Appendicitis. AB - BACKGROUND: There has been an increase in the use of imaging modalities to diagnose appendicitis despite evidence that can help identify children at especially high or low risk of appendicitis who may not benefit. We hypothesized that the passive diffusion of a standardized care pathway (including diagnostic imaging recommendations) would improve the diagnostic workup of appendicitis by safely decreasing the use of unnecessary imaging when compared with historical controls and that an electronic, real-time decision support tool would decrease unnecessary imaging. METHODS: We used an interrupted time series trial to compare proportions of patients who underwent diagnostic imaging (computed tomography [CT] and ultrasound) between 3 time periods: baseline historical controls, after passive diffusion of a diagnostic workup clinical pathway, and after introduction of an electronic medical record-embedded clinical decision support tool that provides point-of-care imaging recommendations (active intervention). RESULTS: The moderate- and high-risk groups showed lower proportions of CT in the passive and active intervention time periods compared with the historical control group. Proportions of patients undergoing ultrasound in all 3 risk groups showed an increase from the historical baseline. Time series analysis confirmed that time trends within any individual time period were not significant; thus, incidental secular trends over time did not appear to explain the decreased use of CT. CONCLUSIONS: Passive and active decision support tools minimized unnecessary CT imaging; long-term effects remain an important area of study. PMID- 27553221 TI - Mobile Phone Interventions for Adolescent Sexual and Reproductive Health: A Systematic Review. AB - CONTEXT: Interventions for adolescent sexual and reproductive health (ASRH) are increasingly using mobile phones but may not effectively report evidence. OBJECTIVE: To assess strategies, findings, and quality of evidence on using mobile phones to improve ASRH by using the mHealth Evidence Reporting and Assessment (mERA) checklist recently published by the World Health Organization mHealth Technical Evidence Review Group. DATA SOURCES: Systematic searches of 8 databases for peer-reviewed studies published January 2000 through August 2014. STUDY SELECTION: Eligible studies targeted adolescents ages 10 to 24 and provided results from mobile phone interventions designed to improve ASRH. DATA EXTRACTION: Studies were evaluated according to the mERA checklist, covering essential mHealth criteria and methodological reporting criteria. RESULTS: Thirty five articles met inclusion criteria. Studies reported on 28 programs operating at multiple levels of the health care system in 7 countries. Most programs (82%) used text messages. An average of 41% of essential mHealth criteria were met (range 14%-79%). An average of 82% of methodological reporting criteria were met (range 52%-100%). Evidence suggests that inclusion of text messaging in health promotion campaigns, sexually transmitted infection screening and follow-up, and medication adherence may lead to improved ASRH. LIMITATIONS: Only 3 articles reported evidence from lower- or middle-income countries, so it is difficult to draw conclusions for these settings. CONCLUSIONS: Evidence on mobile phone interventions for ASRH published in peer-reviewed journals reflects a high degree of quality in methods and reporting. In contrast, current reporting on essential mHealth criteria is insufficient for understanding, replicating, and scaling up mHealth interventions. PMID- 27553222 TI - Transport and Catabolism of Pentitols by Listeria monocytogenes. AB - Transposon insertion into Listeria monocytogenes lmo2665, which encodes an EIIC of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS), was found to prevent D-arabitol utilization. We confirm this result with a deletion mutant and show that Lmo2665 is also required for D-xylitol utilization. We therefore called this protein EIICAxl. Both pentitols are probably catabolized via the pentose phosphate pathway (PPP) because lmo2665 belongs to an operon, which encodes the three PTSAxl components, two sugar-P dehydrogenases, and most PPP enzymes. The two dehydrogenases oxidize the pentitol-phosphates produced during PTS-catalyzed transport to the PPP intermediate xylulose-5-P. L. monocytogenes contains another PTS, which exhibits significant sequence identity to PTSAxl. Its genes are also part of an operon encoding PPP enzymes. Deletion of the EIIC-encoding gene (lmo0508) affected neither D-arabitol nor D-xylitol utilization, although D-arabitol induces the expression of this operon. Both operons are controlled by MtlR/LicR-type transcription activators (Lmo2668 and Lmo0501, respectively). Phosphorylation of Lmo0501 by the soluble PTSAxl components probably explains why D-arabitol also induces the second pentitol operon. Listerial virulence genes are submitted to strong repression by PTS sugars, such as glucose. However, D-arabitol inhibited virulence gene expression only at high concentrations, probably owing to its less efficient utilization compared to glucose. PMID- 27553223 TI - A validation of the National Early Warning Score to predict outcome in patients with COPD exacerbation. AB - BACKGROUND: The National Early Warning Score (NEWS), proposed as a standardised track and trigger system, may perform less well in acute exacerbation of COPD (AECOPD). This study externally validated NEWS and modifications (Chronic Respiratory Early Warning Score (CREWS) and Salford-NEWS) in AECOPD. METHODS: An observational cohort study (2012-2014, two UK acute medical units (AMUs)), compared AECOPD (2361 admissions, 942 individuals, International Statistical Classification of Diseases and Related Health Problems-10 J40-J44 codes) with AMU patients (37 109 admissions, 20 415 individuals). OUTCOME: In-hospital mortality prediction was done by admission NEWS, CREWS and Salford-NEWS assessed by discrimination (area under receiver operating characteristic curves (AUROCs)) and calibration (plots and Hosmer-Lemeshow (H-L) goodness-of-fit). RESULTS: Median admission NEWS in AECOPD was 4 (IQR 2-6) versus 1 (0-3) in AMUs (p<=0.001), despite mortality of 4.5% in both. AECOPD AUROCs were NEWS 0.74 (95% CI 0.66 to 0.82), CREWS 0.72 (0.63 to 0.80) and Salford-NEWS 0.62 (0.53 to 0.70). AMU NEWS AUROC was 0.77 (0.75 to 0.78). At threshold NEWS=5 for AECOPD (44% of admissions), positive predictive value (PPV) of death was 8% (5 to 11) and negative predictive value (NPV) was 98% (97 to 99) versus AMU patients PPV of 17% (16 to 19) and NPV of 97% (97 to 97). For NEWS in AECOPD H-L p value=0.202. CONCLUSION: This first validation of the NEWS in AECOPD found modest discrimination to predict mortality. Lower specificity of NEWS in patients with AECOPD versus other AMU patients reflects acute and chronic respiratory physiological disturbance (including hypoxia), with resultant low PPV at NEWS=5. CREWS and Salford-NEWS, adjusting for chronic hypoxia, increased the specificity and PPV but there was no gain in discrimination. PMID- 27553224 TI - The effect of diabetes control status on treatment response in pulmonary tuberculosis: a prospective study. AB - BACKGROUND: Uncontrolled diabetes, unlike controlled diabetes, is associated with an impaired immune response. However, little is known about the impact of the status of diabetes control on clinical features and treatment outcomes in patients with pulmonary TB (PTB). We conducted this study to evaluate whether the status of diabetes control influences clinical manifestations and treatment responses in PTB. METHODS: A multicentre prospective study was performed between September 2012 and September 2014. The patients were categorised into three groups according to the glycated haemoglobin (HbA1C) level: PTB without diabetes mellitus (non-DM), PTB with controlled diabetes (controlled-DM) and PTB with uncontrolled diabetes (uncontrolled-DM). The primary outcome was the sputum culture conversion rate after 2 months of intensive treatment. RESULTS: Among 661 patients with PTB, 157 (23.8%) had diabetes and 108 (68.8%) had uncontrolled diabetes (HbA1C>=7.0%). The uncontrolled-DM group exhibited more symptoms, positive sputum smears (p<0.001) and presence of cavities (p<0.001) than the non DM group. Regarding treatment responses, patients with uncontrolled-DM were more likely to have a positive culture after 2 months (p=0.009) and either treatment failure (p=0.015) or death (p=0.027) compared with the non-DM group. In contrast, those with controlled-DM showed similar treatment responses to the non-DM group. In multivariable analysis, uncontrolled diabetes was an independent risk factor for a positive sputum culture after 2 months of treatment (adjusted OR, 2.11; p=0.042) and either treatment failure or death (adjusted OR, 4.11; p=0.022). CONCLUSIONS: Uncontrolled diabetes is an independent risk factor for poor treatment response in PTB. PMID- 27553225 TI - Suppression of IGF binding protein-3 by palmitate promotes hepatic inflammatory responses. AB - IGF-binding protein-3 (IGFBP-3) is a liver-derived, anti-inflammatory molecule that is decreased in obesity, a key risk factor for nonalcoholic fatty liver disease (NAFLD). It was not known whether IGFBP-3 levels were altered in NAFLD, whether such alterations could be the result of lipotoxicity, and whether altered IGFBP-3 could affect pathways that are involved in hepatic and systemic inflammation. Serum IGFBP-3 was decreased in patients with NAFLD, whereas liver and circulating IL-8 levels were increased. Palmitate inhibited IGFBP-3 secretion by THP-1 macrophages and enhanced IL-8 expression. Exposure of palmitate-treated THP-1 macrophages to IGFBP-3-deficient conditioned medium led to a 20-fold increase in palmitate-induced IL-8 expression by hepatocytes. Conversely, overexpression of IGFBP-3 suppressed JNK and NF-kappaB activation and blocked palmitate-induced IL-8 expression in hepatocytes. Silencing IGFBP-3 in Huh7 cells enhanced JNK and NF-kappaB activity and increased palmitate-induced IL-8 secretion. These data indicate that IGFBP-3 serves as an anti-inflammatory brake in hepatocytes against JNK and NF-kappaB and limits their activation and downstream production of proinflammatory cytokines. Under lipotoxic conditions, palmitate inhibits hepatic macrophage secretion of IGFBP-3, thereby releasing the brake and enhancing palmitate-induced IL-8 synthesis and secretion.-Min, H.-K., Maruyama, H., Jang, B. K., Shimada, M., Mirshahi, F., Ren, S., Oh, Y., Puri, P., Sanyal, A. J. Suppression of IGF binding protein-3 by palmitate promotes hepatic inflammatory responses. PMID- 27553227 TI - Barriers for Hispanic Caregivers With Obese Preschool Children. AB - INTRODUCTION: Childhood obesity is a growing epidemic, and the rates are disproportionately higher in minorities. Clinical guidelines have contributed to decreased prevalence overall, but the rates in Hispanic preschoolers have increased. METHOD: This review of the literature summarizes the perceptions and beliefs of caregivers of Hispanic preschool children regarding weight status and feeding behaviors, as well as the perceived cultural barriers to guideline adherence. A search of the CINAHL, PubMed, Joanna Briggs, and Global Health databases identified studies performed between January 1, 2008, and April 1, 2016. Search terms included Hispanics, guideline adherence, gap, barriers, obesity, overweight, and attitude to obesity. RESULTS: Fifteen studies met the inclusion criteria, including some about Hispanic caregivers of preschool-aged children. Several cultural perceptions and beliefs were identified. CONCLUSION: Further study is needed to develop more culturally relevant and sensitive guidelines and to design specific and effective interventions for this population. PMID- 27553226 TI - Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration. AB - Neutrophil [polymorphonuclear leukocyte (PMN)] transepithelial migration (TEM) is a hallmark of inflammatory mucosal disorders. PMN TEM is associated with epithelial injury; however, mechanisms involved in this process are not well defined. The current work describes a new mechanism whereby deposition of PMN membrane-derived microparticles (PMN-MPs) onto intestinal epithelial cells (IECs) during TEM leads to loss of epithelial cadherins, thus promoting epithelial injury and increased PMN recruitment. PMN-MPs secreted by activated PMNs during TEM displayed a high level of enzymatically active matrix metalloproteinase 9 (MMP-9), and were capable of mediating potent effects on IEC integrity. Isolated PMN-MPs efficiently bound to IEC monolayers and induced cleavage of desmoglein-2 (DSG-2) but not E-cadherin, leading to disruption of IEC intercellular adhesions. Furthermore, PMN-MP binding to intestinal epithelium in vitro in transwell assays and in vivo in ligated intestinal loop preparations facilitated increases in PMN TEM. These effects were MMP-9 dependent and were reversed in the presence of specific pharmacological inhibitors. Finally, we demonstrated that IEC Dsg-2 serves as a barrier for migrating PMNs, and its removal by PMN-MP-associated MMP 9 facilitates PMN trafficking across epithelial layers. Our findings thus implicate PMN-MPs in PMN-mediated inflammation and epithelial damage, as observed in inflammatory disorders of mucosal surfaces.-Butin-Israeli, V., Houser, M. C., Feng, M., Thorp, E. B., Nusrat, A., Parkos, C. A, Sumagin, R. Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration. PMID- 27553228 TI - Evaluation of the Arthritis Foundation's Camine Con Gusto Program for Hispanic Adults With Arthritis. AB - INTRODUCTION: Camine Con Gusto (CCG) is the Hispanic version of an evidence-based walking program for people with arthritis. This study examined CCG outcomes, feasibility, tolerability, safety, and acceptability and potential tailoring. METHOD: A pre and post 6-week evaluation was conducted in Hispanic people with arthritis. Outcomes included pain, stiffness, fatigue, functional capacity, helplessness, and self-efficacy. A formative evaluation with program participants and key stakeholders explored program tailoring. RESULTS: Participants' mean age was 46.9 years, 44.4% had a high school degree or less, 2.5% were born in United States, 60.1% spoke only Spanish, and 74.7% were female. Moderate effect sizes were found: 0.50 for pain, 0.75 for fatigue, 0.49 for stiffness, 0.33 for function, 0.26 for helplessness, and 0.24 for self-efficacy. There were 285 participants recruited with an 82% 6-week retention (feasibility), no adverse events were reported (safety), and 98% reported program satisfaction (acceptability). Recommended adaptations included simpler language, more pictures and content addressing nutrition and chronic conditions, shortened materials, and inclusion of motivational strategies. CONCLUSION: CCG showed improvement in outcomes in Hispanic individuals comparable to those noted in non-Hispanic White and Black individuals with arthritis. PMID- 27553231 TI - Expression Screening of Integral Membrane Proteins by Fusion to Fluorescent Reporters. AB - The production of recombinant integral membrane proteins for structural and functional studies remains technically challenging due to their relatively low levels of expression. To address this problem, screening strategies have been developed to identify the optimal membrane sequence and expression host for protein production. A common approach is to genetically fuse the membrane protein to a fluorescent reporter, typically Green Fluorescent Protein (GFP) enabling expression levels, localization and detergent solubilisation to be assessed. Initially developed for screening the heterologous expression of bacterial membrane proteins in Escherichia coli, the method has been extended to eukaryotic hosts, including insect and mammalian cells. Overall, GFP-based expression screening has made a major impact on the number of membrane protein structures that have been determined in the last few years. PMID- 27553229 TI - Mutation in S6 domain of HCN4 channel in patient with suspected Brugada syndrome modifies channel function. AB - Diseases such as the sick sinus and the Brugada syndrome are cardiac abnormalities, which can be caused by a number of genetic aberrances. Among them are mutations in HCN4, a gene, which encodes the hyperpolarization-activated, cyclic nucleotide-gated ion channel 4; this pacemaker channel is responsible for the spontaneous activity of the sinoatrial node. The present genetic screening of patients with suspected or diagnosed Brugada or sick sinus syndrome identified in 1 out of 62 samples the novel mutation V492F. It is located in a highly conserved site of hyperpolarization-activated cyclic nucleotide-gated (HCN)4 channel downstream of the filter at the start of the last transmembrane domain S6. Functional expression of mutant channels in HEK293 cells uncovered a profoundly reduced channel function but no appreciable impact on channel synthesis and trafficking compared to the wild type. The inward rectifying HCN4 current could be partially rescued by an expression of heteromeric channels comprising wt and mutant monomers. These heteromeric channels were responsive to cAMP but they required a more negative voltage for activation and they exhibited a lower current density than the wt channel. This suggests a dominant negative effect of the mutation in patients, which carry this heterozygous mutation. Such a modulation of HCN4 activity could be the cause of the diagnosed cardiac abnormality. PMID- 27553232 TI - Detergents in Membrane Protein Purification and Crystallisation. AB - Detergents play a significant role in structural and functional characterisation of integral membrane proteins (IMPs). IMPs reside in the biological membranes and exhibit a great variation in their structural and physical properties. For in vitro biophysical studies, structural and functional analyses, IMPs need to be extracted from the membrane lipid bilayer environment in which they are found and purified to homogeneity while maintaining a folded and functionally active state. Detergents are capable of successfully solubilising and extracting the IMPs from the membrane bilayers. A number of detergents with varying structure and physicochemical properties are commercially available and can be applied for this purpose. Nevertheless, it is important to choose a detergent that is not only able to extract the membrane protein but also provide an optimal environment while retaining the correct structural and physical properties of the protein molecule. Choosing the best detergent for this task can be made possible by understanding the physical and chemical properties of the different detergents and their interaction with the IMPs. In addition, understanding the mechanism of membrane solubilisation and protein extraction along with crystallisation requirements, if crystallographic studies are going to be undertaken, can help in choosing the best detergent for the purpose. This chapter aims to present the fundamental properties of detergents and highlight information relevant to IMP crystallisation. The first section of the chapter reviews the physicochemical properties of detergents and parameters essential for predicting their behaviour in solution. The second section covers the interaction of detergents with the biologic membranes and proteins followed by their role in membrane protein crystallisation. The last section will briefly cover the types of detergent and their properties focusing on custom designed detergents for membrane protein studies. PMID- 27553230 TI - Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice. AB - Recently, we reported a correlation of scopolamine mediated decline in memory consolidation with increase in the expression of DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in the mouse hippocampus. Memory consolidation is a protein synthesis-dependent process which involves the expression of synaptic plasticity genes, particularly neuronal immediate early genes (IEGs). However, the mechanism of regulation of these genes during decline in memory is poorly understood. Therefore, we have studied the epigenetic regulation of expression of neuronal IEGs in scopolamine-induced amnesic mice. Scopolamine significantly impaired memory consolidation as tested by radial arm maze, and the expression of neuronal IEGs was downregulated in the hippocampus as revealed by qRT-PCR and Western blotting. Further, methylated DNA immunoprecipitation (MeDIP) analysis showed increase in DNA methylation, while chromatin immunoprecipitation (ChIP) revealed decrease in H3K9/14 acetylation at the promoter of neuronal IEGs. Taken together, the present study shows that increased DNA methylation and decreased histone acetylation at the promoter of neuronal IEGs are associated with decline in their expression and memory consolidation during scopolamine induced amnesia. These findings suggest that the epigenetic regulation through altered DNA methylation and histone acetylation might be explored further to develop potential therapeutic interventions for amnesia. PMID- 27553233 TI - NMR of Membrane Proteins: Beyond Crystals. AB - Membrane proteins are essential for the flow of signals, nutrients and energy between cells and between compartments of the cell. Their mechanisms can only be fully understood once the precise structures, dynamics and interactions involved are defined at atomic resolution. Through advances in solution and solid state NMR spectroscopy, this information is now available, as demonstrated by recent studies of stable peripheral and transmembrane proteins. Here we highlight recent cases of G-protein coupled receptors, outer membrane proteins, such as VDAC, phosphoinositide sensors, such as the FAPP-1 pleckstrin homology domain, and enzymes including the metalloproteinase MMP-12. The studies highlighted have resulted in the determination of the 3D structures, dynamical properties and interaction surfaces for membrane-associated proteins using advanced isotope labelling strategies, solubilisation systems and NMR experiments designed for very high field magnets. Solid state NMR offers further insights into the structure and multimeric assembly of membrane proteins in lipid bilayers, as well as into interactions with ligands and targets. Remaining challenges for wider application of NMR to membrane structural biology include the need for overexpression and purification systems for the production of isotope-labelled proteins with fragile folds, and the availability of only a few expensive perdeuterated detergents.Step changes that may transform the field include polymers, such as styrene maleic acid, which obviate the need for detergent altogether, and allow direct high yield purification from cells or membranes. Broader demand for NMR may be facilitated by MODA software, which instantly predicts membrane interactive residues that can subsequently be validated by NMR. In addition, recent developments in dynamic nuclear polarization NMR instrumentation offer a remarkable sensitivity enhancement from low molarity samples and cell surfaces. These advances illustrate the current capabilities and future potential of NMR for membrane protein structural biology and ligand discovery. PMID- 27553234 TI - Characterisation of Conformational and Ligand Binding Properties of Membrane Proteins Using Synchrotron Radiation Circular Dichroism (SRCD). AB - Membrane proteins are notoriously difficult to crystallise for use in X-ray crystallographic structural determination, or too complex for NMR structural studies. Circular dichroism (CD) is a fast and relatively easy spectroscopic technique to study protein conformational behaviour in solution. The advantage of synchrotron radiation circular dichroism (SRCD) measured with synchrotron beamlines compared to the CD from benchtop instruments is the extended spectral far-UV region that increases the accuracy of secondary structure estimations, in particular under high ionic strength conditions. Membrane proteins are often available in small quantities, and for this SRCD measured at the Diamond B23 beamline has successfully facilitated molecular recognition studies. This was done by probing the local tertiary structure of aromatic amino acid residues upon addition of chiral or non-chiral ligands using long pathlength cells (1-5 cm) of small volume capacity (70 MUl-350 MUl). In this chapter we describe the use of SRCD to qualitatively and quantitatively screen ligand binding interactions (exemplified by Sbma, Ace1 and FsrC proteins); to distinguish between functionally similar drugs that exhibit different mechanisms of action towards membrane proteins (exemplified by FsrC); and to identify suitable detergent conditions to observe membrane protein-ligand interactions using stabilised proteins (exemplified by inositol transporters) as well as the stability of membrane proteins (exemplified by GalP, Ace1). The importance of the in solution characterisation of the conformational behaviour and ligand binding properties of proteins in both far- andnear-UV regions and the use of high-throughput CD (HT CD) using 96- and 384-well multiplates to study the folding effects in various protein crystallisation buffers are also discussed. PMID- 27553235 TI - Membrane Protein Crystallisation: Current Trends and Future Perspectives. AB - Alpha helical membrane proteins are the targets for many pharmaceutical drugs and play important roles in physiology and disease processes. In recent years, substantial progress has been made in determining their atomic structure using X ray crystallography. However, a major bottleneck still remains; the identification of conditions that give crystals that are suitable for structure determination. Over the past 10 years we have been analysing the crystallisation conditions reported for alpha helical membrane proteins with the aim to facilitate a rational approach to the design and implementation of successful crystallisation screens. The result has been the development of MemGold, MemGold2 and the additive screen MemAdvantage. The associated analysis, summarised and updated in this chapter, has revealed a number of surprisingly successfully strategies for crystallisation and detergent selection. PMID- 27553237 TI - Nonlinear Optical Characterization of Membrane Protein Microcrystals and Nanocrystals. AB - Nonlinear optical methods such as second harmonic generation (SHG) and two-photon excited UV fluorescence (TPE-UVF) imaging are promising approaches to address bottlenecks in the membrane protein structure determination pipeline. The general principles of SHG and TPE-UVF are discussed here along with instrument design considerations. Comparisons to conventional methods in high throughput crystallization condition screening and crystal quality assessment prior to X-ray diffraction are also discussed. PMID- 27553236 TI - Crystal Dehydration in Membrane Protein Crystallography. AB - Crystal dehydration has been successfully implemented to facilitate the structural solution of a number of soluble and membrane protein structures over the years. This chapter will present the currently available tools to undertake controlled crystal dehydration, focusing on some successful membrane protein cases. Also discussed here will be some practical considerations regarding membrane protein crystals and the relationship between different techniques in order to help researchers to select the most suitable technique for their projects. PMID- 27553238 TI - Exploiting Microbeams for Membrane Protein Structure Determination. AB - A reproducible, and sample independent means of predictably obtaining large, well ordered crystals has proven elusive in macromolecular crystallography. In the structure determination pipeline, crystallisation often proves to be a rate limiting step, and the process of obtaining even small or badly ordered crystals can prove time-consuming and laborious. This is particularly true in the field of membrane protein crystallography and this is reflected in the limited number of unique membrane protein structures deposited in the protein data bank (less than 650 by June 2016 - http://blanco.biomol.uci.edu/mpstruc ). Over recent years the requirement for, and time and cost associated with obtaining, large crystals has been partially alleviated through the development of beamline instrumentation allowing data collection, and structure solution, from ever-smaller crystals. Advances in several areas have led to a step change in what might be considered achievable during a synchrotron trip over the last decade. This chapter will briefly review the current status of the field, the tools available to ease data collection and processing, and give some examples of exploitation of these for membrane protein microfocus macromolecular crystallography. PMID- 27553239 TI - Applications of the BLEND Software to Crystallographic Data from Membrane Proteins. AB - X-ray diffraction from crystals of membrane proteins very often yields incomplete datasets due to, among other things, severe radiation damage. Multiple crystals are thus required to form complete datasets, provided the crystals themselves are isomorphous. Selection and combination of data from multiple crystals is a difficult and tedious task that can be facilitated by purpose-built software. BLEND, in the CCP4 suite of programs for macromolecular crystallography (MX), has been created exactly for this reason. In this chapter the program is described and its workings illustrated by means of data from two membrane proteins. PMID- 27553240 TI - Serial Millisecond Crystallography of Membrane Proteins. AB - Serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs) is a powerful method to determine high-resolution structures of pharmaceutically relevant membrane proteins. Recently, the technology has been adapted to carry out serial millisecond crystallography (SMX) at synchrotron sources, where beamtime is more abundant. In an injector-based approach, crystals grown in lipidic cubic phase (LCP) or embedded in viscous medium are delivered directly into the unattenuated beam of a microfocus beamline. Pilot experiments show the application of microjet-based SMX for solving the structure of a membrane protein and compatibility of the method with de novo phasing. Planned synchrotron upgrades, faster detectors and software developments will go hand-in-hand with developments at free-electron lasers to provide a powerful methodology for solving structures from microcrystals at room temperature, ligand screening or crystal optimization for time-resolved studies with minimal or no radiation damage. PMID- 27553241 TI - Serial Femtosecond Crystallography of Membrane Proteins. AB - Membrane proteins, including G protein-coupled receptors (GPCRs), constitute the most important drug targets. The increasing number of targets requires new structural information, which has proven tremendously challenging due to the difficulties in growing diffraction-quality crystals. Recent developments of serial femtosecond crystallography at X-ray free electron lasers combined with the use of membrane-mimetic gel-like matrix of lipidic cubic phase (LCP-SFX) for crystal growth and delivery hold significant promise to accelerate structural studies of membrane proteins. This chapter describes the development and current status of the LCP-SFX technology and elaborates its future role in structural biology of membrane proteins. PMID- 27553243 TI - Identification of the Phenol Functionality in Deprotonated Monomeric and Dimeric Lignin Degradation Products via Tandem Mass Spectrometry Based on Ion-Molecule Reactions with Diethylmethoxyborane. AB - Conversion of lignin into smaller molecules provides a promising alternate and sustainable source for the valuable chemicals currently derived from crude oil. Better understanding of the chemical composition of the resulting product mixtures is essential for the optimization of such conversion processes. However, these mixtures are complex and contain isomeric molecules with a wide variety of functionalities, which makes their characterization challenging. Tandem mass spectrometry based on ion-molecule reactions has proven to be a powerful tool in functional group identification and isomer differentiation for previously unknown compounds. This study demonstrates that the identification of the phenol functionality, the most commonly observed functionality in lignin degradation products, can be achieved via ion-molecule reactions between diethylmethoxyborane (DEMB) and the deprotonated analyte in the absence of strongly electron withdrawing substituents in the ortho- and para-positions. Either a stable DEMB adduct or an adduct that has lost a methanol molecule (DEMB adduct-MeOH) is formed for these ions. Deprotonated phenols with an adjacent phenol or hydroxymethyl functionality or a conjugated carboxylic acid functionality can be identified based on the formation of DEMB adduct-MeOH. Deprotonated compounds not containing the phenol functionality and phenols containing an electron withdrawing ortho- or para-substituent were found to be unreactive toward diethylmethoxyborane. Hence, certain deprotonated isomeric compounds with phenol and carboxylic acid, aldehyde, carboxylic acid ester, or nitro functionalities can be differentiated via these reactions. The above mass spectrometry method was successfully coupled with high-performance liquid chromatography for the analysis of a complex biomass degradation mixture. Graphical Abstract ?. PMID- 27553242 TI - Beyond Membrane Protein Structure: Drug Discovery, Dynamics and Difficulties. AB - Most of the previous content of this book has focused on obtaining the structures of membrane proteins. In this chapter we explore how those structures can be further used in two key ways. The first is their use in structure based drug design (SBDD) and the second is how they can be used to extend our understanding of their functional activity via the use of molecular dynamics. Both aspects now heavily rely on computations. This area is vast, and alas, too large to consider in depth in a single book chapter. Thus where appropriate we have referred the reader to recent reviews for deeper assessment of the field. We discuss progress via the use of examples from two main drug target areas; G-protein coupled receptors (GPCRs) and ion channels. We end with a discussion of some of the main challenges in the area. PMID- 27553244 TI - Patient experiences and the association with organizational factors in general practice: results from the Norwegian part of the international, multi-centre, cross-sectional QUALICOPC study. AB - BACKGROUND: General practitioners (GPs) constitute a vital part of a strong primary health care system. We need further knowledge concerning factors that may affect the patients' experiences in their meetings with the GPs. We investigated to what degree organizational factors and GP characteristics are associated with patients' communicative experiences in a consultation. METHODS: We used data from the Norwegian part of the international, multi-center study Quality and Costs of Primary Care in Europe (QUALICOPC). We included 198 Norwegian GPs and 1529 patients. The patients completed a survey concerning experiences in a consultation with a GP on the inclusion day. The GPs completed a survey regarding organizational aspects of their own practice. Main outcome measures were seven statements concerning how the patients experienced the communication with the GP during the consultation. A generalized estimating equation logistic regression model was used to identify variations in patient experiences associated with characteristics of the GPs and their practices. RESULTS: The patients reported overall positive experiences with their GP consultations. Patients who consulted a GP with a short patient list were less likely than patients who consulted a GP with a medium sized list to regard the GP as polite (Odds Ratio (OR) 0.2; 95 % CI 0.1-0.7), to report that the GP asked questions about their health problems (OR 0.6; 0.4-1.0) or that the GP used sufficient time (OR 0.5; CI 0.3-0.9). Patients who consulted a GP with a long patient list compared to patients who consulted a GP with a medium sized list were less likely to feel that they could cope better after the GP visit (OR 0.5; 0.3-0.9) and more likely to feel that the GP hardly looked at them while talking (OR 1.8; 1.0-3.0). No associations with patient experiences were found with the average duration of the consultations, whether the GP worked in a fee-for-service model or whether the GP was the patient's regular doctor. CONCLUSIONS: Norwegian patients report predominantly positive experiences when consulting a GP. Positive communication experiences are most likely to be reported when the GP has a medium sized patient list. PMID- 27553245 TI - Species composition and insecticide resistance status of Anopheles gambiae (s.l.) (Culicidae) in Kome, southern Chad and the implications for malaria control. AB - BACKGROUND: The development and spread of insecticide resistance among malaria vectors, is a threat to the continued effectiveness of interventions to control and eliminate the disease. The status of insecticide resistance among malaria vector populations at two sites in Kome, southern Chad, was evaluated to inform decisions on vector control. METHODS: Mosquito larvae were collected from temporary rain-filled and semi-permanent breeding places at two sites and reared in a laboratory. Emerging Anopheles gambiae (senso lato) (s.l.) adults were morphologically identified, sorted and evaluated for susceptibility to WHOPES recommended insecticides. Standardized biomolecular and biochemical methods were used to determine sibling species and molecular forms: knockdown resistant alleles (kdr-w) for pyrethroids and DDT; acetylcholinesterase-1 resistant alleles for organophosphate and carbamates; biochemical resistance through measurement of the levels of non-specific esterase (alpha and beta), oxidase and glutathione-s transferases activities. RESULTS: Anopheles gambiae (s.l.) was the main vector group in the two study sites and comprised of Anopheles gambiae (senso stricto) (s.s.) and An. arabiensis, respectively, at 71 and 29 % in Site A, and 60 and 40 % at Site B. Anopheles gambiae (s.s.) was composed of M (Anopheles coluzzii) and S [nominotypical An. gambiae (s.s.)] molecular forms. Anopheles coluzzii accounted for over 98 % of the sub-group. There was extensive phenotypic resistance to pyrethroids, DDT and carbamates, but full susceptibility to organophosphates. Population-wide frequency of knockdown resistant allele in An. gambiae (s.l.) was 43 homozygous (RR), 19 heterozygous (RS) and 38 % homozygous susceptible (SS). When segregated by species and molecular forms, An. coluzzii had the highest kdr-w frequency of 37.4 homozygous resistant alleles, and 17.5 % heterozygous, with 8.3 % homozygote susceptible alleles. An. gambiae (s.s.) had 1 % homozygous resistant allele. Levels of esterase, oxidase and glutathione-s transferases were not significantly different compared to fully susceptible laboratory raised An. gambiae (s.s.) Kisumu reference, although few individuals showed significant elevation of esterases (> 0.04 MUg/protein), indicating a likely start of biochemical enzyme resistance. CONCLUSIONS: There is an urgent need for action to stop and reverse significant insecticide resistance in the area. A comprehensive entomological surveillance and monitoring program is needed to understand the full extent of resistance to enable realistic insecticide resistance management strategy, and also to track future changes in the vector populations. PMID- 27553247 TI - A case of a duplicated superficial branch of radial nerve and a two-bellied brachioradialis muscle presenting a potential entrapment syndrome. AB - We have found an interesting coincidental variation of the superficial branch of the radial nerve and the brachioradialis muscle in a male cadaver. The superficial branch of the radial nerve was duplicated with one branch taking an aberrant course between two bellies of the brachioradialis muscle. The variant brachioradialis muscle featured two muscle bellies, a superficial one and a deep one, with one common origin and one common insertional tendon. The accessory nerve branch was impinged by two blood vessels and pierced through muscle bundles connecting two bellies of the brachioradialis muscle. The knowledge of this neuromuscular variant is of clinical relevance for the differential diagnosis of pain and paresthesia on the dorsoradial aspect of the hand and for the surgical management of the Wartenberg's syndrome. PMID- 27553246 TI - Multi-environment QTL studies suggest a role for cysteine-rich protein kinase genes in quantitative resistance to blackleg disease in Brassica napus. AB - BACKGROUND: Resistance to the blackleg disease of Brassica napus (canola/oilseed rape), caused by the hemibiotrophic fungal pathogen Leptosphaeria maculans, is determined by both race-specific resistance (R) genes and quantitative resistance loci (QTL), or adult-plant resistance (APR). While the introgression of R genes into breeding material is relatively simple, QTL are often detected sporadically, making them harder to capture in breeding programs. For the effective deployment of APR in crop varieties, resistance QTL need to have a reliable influence on phenotype in multiple environments and be well defined genetically to enable marker-assisted selection (MAS). RESULTS: Doubled-haploid populations produced from the susceptible B. napus variety Topas and APR varieties AG-Castle and AV Sapphire were analysed for resistance to blackleg in two locations over 3 and 4 years, respectively. Three stable QTL were detected in each population, with two loci appearing to be common to both APR varieties. Physical delineation of three QTL regions was sufficient to identify candidate defense-related genes, including a cluster of cysteine-rich receptor-like kinases contained within a 49 gene QTL interval on chromosome A01. Individual L. maculans isolates were used to define the physical intervals for the race-specific R genes Rlm3 and Rlm4 and to identify QTL common to both field studies and the cotyledon resistance response. CONCLUSION: Through multi-environment QTL analysis we have identified and delineated four significant and stable QTL suitable for MAS of quantitative blackleg resistance in B. napus, and identified candidate genes which potentially play a role in quantitative defense responses to L. maculans. PMID- 27553248 TI - Screening and risk assessment for coronary artery disease in HIV infection: an unmet need. AB - HIV infection is now considered a chronic, treatable disease, although treatment is associated with increased rates of coronary artery disease (CAD). Increased risk of CAD in HIV-infected patients has been associated with the inflammatory sequelae of the infection as well as the greater prevalence of cardiac risk factors in HIV-positive populations and the side effects of life-prolonging antiretroviral therapies. Patients with HIV infection now have a 1.5 to 2-fold greater risk of developing CAD compared with noninfected individuals, raising the independent risk of CAD in HIV infection to levels similar to those in diabetes. Despite this increased risk, screening and other adjuvant assessment tools are lacking. In this paper we explore the current climate of CAD in the contemporary HIV-infected population and look at the tools used in the assessment and management of patients as well as the limitations of these approaches for this at risk population group. PMID- 27553249 TI - Seed Dispersal of Threatened Tree Species by a Critically Endangered Primate in a Brazilian Hotspot. AB - In the northern Atlantic Forest, hunting and habitat loss have eliminated most large mammals that disperse zoochoric fruits. Due to the decrease in populations of large seed dispersers, yellow-breasted capuchins (Sapajusxanthosternos) are currently one of the largest arboreal fruit-eating mammals in the region. During 26 months, we followed 14-25 capuchins aiming to (1) present data on their dietary ecology, (2) verify the conservation status of plants in the diet, and (3) determine distance and habitat of seed deposition based on gut retention time. Capuchins showed a preference for feeding in old secondary forests in spite of the greater availability of primary forests. They fed on 109 species of fruits (42.7% of feeding frequency) and swallowed 85 species of seeds (mean width: 0.73 +/- 0.57 cm; mean length: 1.17 +/- 0.83 cm). Capuchins consumed mostly oil palm and manilkara fruits. We observed long distances of seed deposition (median 300 360 m); 36.8-41.7% of these events occurred in a distinct habitat, and seeds of 12 late-stage trees swallowed in the primary forest were deposited in old secondary forests. S. xanthosternos has an important role in the first phase of seed dispersal (seed removal from the parent tree and seed deposition), particularly for 23 endemic and 3 endangered plants. PMID- 27553250 TI - Removal of herbicidal ionic liquids by electrochemical advanced oxidation processes combined with biological treatment. AB - Recently a new group of ionic liquids (ILs) with herbicidal properties has been proposed for use in agriculture. Owing to the design of specific physicochemical properties, this group, referred to as herbicidal ionic liquids (HILs), allows for reducing herbicide field doses. Several ILs comprising phenoxy herbicides as anions and quaternary ammonium cations have been synthesized and tested under greenhouse and field conditions. However, since they are to be introduced into the environment, appropriate treatment technologies should be developed in order to ensure their proper removal and avoid possible contamination. In this study, didecyldimethylammonium (4-chloro-2-methylphenoxy) acetate was selected as a model HIL to evaluate the efficiency of a hybrid treatment method. Electrochemical oxidation or electro-Fenton was considered as a pretreatment step, whereas biodegradation was selected as the secondary treatment method. Both processes were carried out in current mode, at 10 mA with carbon felt as working electrode. The efficiency of degradation, oxidation and mineralization was evaluated after 6 h. Both processes decreased the total organic carbon and chemical oxygen demand (COD) values and increased the biochemical oxygen demand (BOD5) on the COD ratio to a value close to 0.4, showing that the electrolyzed solutions can be considered as 'readily biodegradable.' PMID- 27553251 TI - The Significance of Lewis Acid Sites for the Selective Catalytic Reduction of Nitric Oxide on Vanadium-Based Catalysts. AB - The long debated reaction mechanisms of the selective catalytic reduction (SCR) of nitric oxide with ammonia (NH3 ) on vanadium-based catalysts rely on the involvement of Bronsted or Lewis acid sites. This issue has been clearly elucidated using a combination of transient perturbations of the catalyst environment with operando time-resolved spectroscopy to obtain unique molecular level insights. Nitric oxide reacts predominantly with NH3 coordinated to Lewis sites on vanadia on tungsta-titania (V2 O5 -WO3 -TiO2 ), while Bronsted sites are not involved in the catalytic cycle. The Lewis site is a mono-oxo vanadyl group that reduces only in the presence of both nitric oxide and NH3 . We were also able to verify the formation of the nitrosamide (NH2 NO) intermediate, which forms in tandem with vanadium reduction, and thus the entire mechanism of SCR. Our experimental approach, demonstrated in the specific case of SCR, promises to progress the understanding of chemical reactions of technological relevance. PMID- 27553252 TI - Diffusion-weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility, repeatability, and diagnostic accuracy. AB - Diffusion-weighted MRI (DWI) provides insights into tissue microstructure by visualization and quantification of water diffusivity. Quantitative evaluation of the apparent diffusion coefficient (ADC) obtained from DWI has been proven helpful for differentiating between malignant and benign breast lesions, for cancer subtyping in breast cancer patients, and for prediction of response to neoadjuvant chemotherapy. However, to further establish DWI of breast lesions it is important to evaluate the quantitative imaging biomarker (QIB) characteristics of reproducibility, repeatability, and diagnostic accuracy. In this intra individual prospective clinical study 40 consecutive patients with suspicious findings, scheduled for biopsy, underwent an identical 3T breast MRI protocol of the breast on two consecutive days (>24 h). Mean ADC of target lesions was assessed (two independent readers) in four separate sessions. Reproducibility, repeatability, and diagnostic accuracy between examinations (E1, E2), readers (R1, R2), and measurements (M1, M2) were assessed with intraclass correlation coefficients (ICCs), coefficients of variation (CVs), Bland-Altman plots, and receiver operating characteristic (ROC) analysis with calculation of the area under the ROC curve (AUC). The standard of reference was either histopathology (n = 38) or imaging follow-up of up to 24 months (n = 2). Eighty breast MRI examinations (median E1-E2, 2 +/- 1.7 days, 95% confidence interval (CI) 1-2 days, range 1-11 days) in 40 patients (mean age 56, standard deviation (SD) +/ 14) were evaluated. In 55 target lesions (mean size 25.2 +/- 20.8 (SD) mm, range 6-106 mm), mean ADC values were significantly (P < 0.0001) higher in benign (1.38, 95% CI 1.27-1.49 * 10(-3) mm(2) /s) compared with malignant (0.86, 95% CI 0.81-0.91 * 10(-) (3) mm(2) /s) lesions. Reproducibility and repeatability showed high agreement for repeated examinations, readers, and measurements (all ICCs >0.9, CVs 3.2-8%), indicating little variation. Bland-Altman plots demonstrated no systematic differences, and diagnostic accuracy was not significantly different in the two repeated examinations (all ROC curves >0.91, P > 0.05). High reproducibility, repeatability, and diagnostic accuracy of DWI provide reliable characteristics for its use as a potential QIB, to further improve breast lesion detection, characterization, and treatment monitoring of breast lesions. PMID- 27553253 TI - Are online symptoms checkers useful for patients with inflammatory arthritis? AB - BACKGROUND: Online symptom checkers are increasingly used by patients however there is little published evidence of their effectiveness in real patients. The aim of this study was to evaluate how patients with inflammatory arthritis and inflammatory arthralgia use the internet to look for health information and to assess the advice given and diagnoses suggested by the NHS and WebMD symptom checkers in relation to the patients' actual diagnoses. METHODS: Thirty-four patients with inflammatory arthritis (rheumatoid arthritis (n = 13), psoriatic arthritis (n = 4), unclassified arthritis (n = 4)) and inflammatory arthralgia (n = 13) newly presenting to a secondary care based clinic were identified using a consecutive sampling approach. Consenting patients were asked questions about their internet use in relation to their presenting symptoms. They then completed the NHS and the WebMD symptom checkers and their answers and the outcomes were recorded. RESULTS: Sixteen patients had previously consulted the internet regarding their symptoms. Neither age nor gender significantly influenced internet usage. Actions advised via the NHS symptom checker were: call an ambulance (n = 11), attend A&E (n = 4), contact your GP straight away (n = 2), see your GP today (n = 6), or see your GP within 36 h (n = 11). The 5 most common differential diagnoses given by Web MD were gout (n = 28), rheumatoid arthritis (n = 24), psoriatic arthritis (n = 22), osteoarthritis (n = 18) and finger dislocation (n = 10). The most common first differential diagnosis was osteoarthritis (n = 12). Only 4 out of 21 patients with inflammatory arthritis were given a first diagnosis of rheumatoid arthritis or psoriatic arthritis. CONCLUSIONS: Our data highlight that help seeking advice given online is often inappropriate and that the diagnoses suggested are frequently inaccurate. Recommendations to seek emergency advice may cause inappropriate healthcare utilization. PMID- 27553255 TI - A prospective clinical cohort study analyzing single-unit implant crowns after three years of loading: introduction of a novel Functional Implant Prosthodontic Score (FIPS). AB - OBJECTIVES: The aim of this prospective clinical cohort study was to validate implant crowns with a novel Functional Implant Prosthodontic Score (FIPS). MATERIAL AND METHODS: Twenty patients were restored with cement-retained crowns on soft tissue level implants (Institut Straumann AG, Basel, Switzerland) in posterior sites and annually followed-up for 3 years. FIPS was applied for the objective outcome assessment including clinical and radiographic examinations. Five variables were defined for evaluation, resulting in a maximum score of 10 per implant restoration. The patients' level of satisfaction was recorded and correlated with FIPS. RESULTS: All implants and connected crowns revealed survival rates of 100% without any biological or technical complications after three years of loading. The mean total FIPS score was 7.8 +/- 1.5, ranging from 6 to 10. The variable "bone" revealed the highest scores (2 +/- 0; range: 2-2), followed by "occlusion" (1.9 +/- 0.1; range: 1-2). Mean scores for "design" (1.2 +/- 0.6; range: 0-2), "mucosa" (1.3 +/- 0.7; range: 0-2), and "interproximal" (1.4 +/- 0.4; range: 1-2) were more challenging to satisfy. The patients expressed a high level of functional satisfaction (84.1 +/- 9.5; range: 68-100). A significant correlation was found between FIPS and the subjective patients' perception with a coefficient of 0.88 (P < 0.0001). CONCLUSIONS: The findings of the clinical trial indicated the potential of FIPS as an objective and reliable instrument in assessing implant success. FIPS can be considered as a supportive tool to validate a satisfactory outcome as perceived by patients, to identify possible failure risks, and to compare follow-up observations. PMID- 27553254 TI - Differentiation potential of rabbit CD90-positive cells sorted from adipose derived stem cells in vitro. AB - To investigate the differentiation potential of purified CD90+ cells sorted from adipose-derived stem cells (ADSCs), CD90+ cells were sorted from rabbit ADSCs using flow cytometry. Then, cell expansion of CD90+ cells and unsorted ADSCs was observed using an inverted microscope. Furthermore, cell surface markers including CD40, CD105, and CD90 on CD90+ cells and unsorted ADSCs were quantified using flow cytometry. Additionally, multi-lineage differentiation ability between CD90+ cells and unsorted ADSCs was compared, and expression of adipocyte-related genes PPAR-r and CEBPA as well as stem cell-related gene SOX2 in CD90+ cells and unsorted ADSCs was determined using real-time quantitative PCR. We found that CD90+ cells had a stronger cell proliferation ability than unsorted ADSCs. CD90+ cells showed a stronger ability of osteoblast and chondrocyte differentiation than unsorted ADSCs and CD90- cells, whereas the adipose differentiation ability of CD90+ cells was similar to that of ADSCs and CD90- cells. CD14, CD105, and CD90 on CD90+ cells were expressed more highly than those on ADSCs. Additionally, the mRNA expression level of SOX2 in CD90+ cells was significantly higher than that in ADSCs, whereas the expression of PPAR-r and CEBPA was markedly lower than that in ADSCs. These results suggested that the purified CD90+ cells sorted from ADSCs exhibit a stronger differentiation potential than the unsorted ADSCs. PMID- 27553256 TI - [Vaccination coverage and socioeconomic determinants of BCG vaccination in children before 3 months: Results of the Elfe cohort study, 2011]. AB - BACKGROUND: In 2007, French authorities changed mandatory BCG vaccination for all children into a strong recommendation to vaccinate only children considered at high risk of tuberculosis. Vaccination coverage (VC) data are insufficient in France. We estimated VC at approximately two months of age and identified socioeconomic factors associated with BCG vaccination. METHODS: The Elfe study (Etude Longitudinale Francaise depuis l'Enfance) included a random sample of about 18 000 children born in 2011 selected at birth from 320 maternity wards from mainland France. Information was collected through questionnaires and telephone interviews conducted approximately two months after delivery. Because BCG recommendations are different in the Paris region (Ile-de-France [IDF]) and outside this region, VC was estimated separately in these two regions. We estimated VC for different levels of tuberculosis risk, approached by the geographical origin of the parents. Poisson regression was performed to analyze the association between socioeconomic factors and BCG vaccination status, and results expressed by prevalence ratios (PR). RESULTS: CV was higher in IDF (59.5%) compared to at-risk children outside IDF (46.7%) (p<0.001). VC in children with two parents from a tuberculosis highly endemic country was 80.5% in IDF and 60.4% outside IDF. In the multivariable model, having one or two parents from a tuberculosis highly endemic country (PR around 1.40) or consulting a private pediatrician (PR around 1.15) or a maternal and child health (MCH) center (PR around 1.40) after leaving the maternity ward were associated with a higher VC, whereas a university educational level in mothers was associated with a lower VC (PR=0.80). CONCLUSION: In France, BCG vaccination in infants is performed early after discharge from the maternity ward. A first consultation with a pediatrician or in a MCH center is associated with better vaccination coverage. Children at higher risk are probably well identified by physicians and better vaccinated. PMID- 27553257 TI - Scalable Fabrication of Multiplexed Plasmonic Nanoparticle Structures Based on AFM Lithography. AB - A controllable and scalable strategy is developed to fabricate multiplexed plasmonic nanoparticle structures by mechanical scratching with AFM lithography, which exhibit multiplex plasmonic properties and surface-enhanced Raman scattering responses. It offers an intuitive way to explore the plasmonic effects on the performance of an organic light-emitting diode device integrating with multiplexed plasmonic nanostructures. PMID- 27553258 TI - Optimized Nonlinear Dynamic Analysis of Pathologic Voices With Laryngeal Paralysis Based on the Minimum Embedding Dimension. AB - OBJECTIVE: The present study aims to compare the correlation dimension and second order entropy at the minimum embedding dimension with the correlation dimension (D2) and second-order entropy (K2) based on their efficiency and accuracy in differentiating between normal and pathologic voices. METHODS: The minimum embedding dimension was estimated with the Cao method. Nonlinear dynamic parameters, such as correlation dimension and second-order entropy, were used to quantitatively analyze the normal and pathologic voice samples. RESULTS: The computing time of the correlation dimension and second-order entropy at the minimum embedding dimension was reduced to approximately one third of that of traditional D2 and K2 calculations, reflecting higher efficiency. The statistical results of linear fitting suggested that the correlation dimension was highly correlated to the correlation dimension at the minimum embedding dimension, and second-order entropy calculation was highly correlated to the second-order entropy at the minimum embedding dimension. Lastly, the results of statistical comparison proved that the correlation dimension at the minimum embedding dimension and second-order entropy at the minimum embedding dimension were able to significantly differentiate between normal and disordered voices (P <0.001). CONCLUSIONS: The results suggest that the correlation dimension and second-order entropy at the minimum embedding dimension are valid analysis tools for the diagnosis of voice disorders. Additionally, the efficiency and accuracy of these parameters yield potential for clinical usage because of lower computation time than current methods. PMID- 27553260 TI - Prevalence and Associated Factors of Depressive Symptoms Among Disadvantaged Adolescents: Results from a Population-Based Study in Bangladesh. AB - PROBLEM: Few studies have examined the adolescents' depression in low-income countries and no research has yet been carried out in Bangladesh. This study estimated the prevalence of depressive symptoms and explored the associated factors and help seeking behavior among adolescents in Bangladesh. METHODS: Data originated from a cross section of 2,440 randomly selected boys and girls aged 13 19 years in a rural district and urban slums of Dhaka city, Bangladesh, during October-November 2012. Beck Depression Inventory (BDI), a 21-item scale, measured the prevalence of depressive symptoms using a cut-off 16 or higher. FINDINGS: The prevalence of depressive symptoms among adolescents was 14%, with predominance in urban slums and among girls. Older age (15-19 years), poverty, and poor parental relation were found to be associated with depressive symptoms of both sexes; family history of depressive symptoms for boys; and reproductive illness and sexual abuse for girls. More than 80% of depressed adolescents sought no help. CONCLUSIONS: Adolescent depressive symptoms are common and largely undetected public health problem in Bangladesh. Policies aimed at concerted efforts for implementing a school-based counseling program with components of cognitive behavioral therapy and developing referral systems for those who scored at least 30 at BDI may ameliorate the potential harmful consequences of depressive symptoms in adolescents. PMID- 27553259 TI - Pregnancy and Birth Outcomes Among Immigrant Women in the US and Europe: A Systematic Review. AB - Human migration is not a new phenomenon, but it has changed significantly with the advance of globalization. We focus on differences in the published literature concerning migration and health (EU vs the US), centering specifically on reproductive health outcomes. We conducted a literature search in the Pubmed and Embase databases. We reviewed papers that contrast migrants to native-born populations and analyzed differences between countries as well as challenges for future research. The prevalence of low birthweight among migrants varies by the host country characteristics as well as the composition of migrants to different regions. The primary driver of migrant health is the migrant "regime" in different countries at specific periods of time. Future health outcomes of immigrants will depend on the societal characteristics (legal protections, institutions and health systems) of host countries. PMID- 27553261 TI - Solid dispersions of efonidipine hydrochloride ethanolate with improved physicochemical and pharmacokinetic properties prepared with microwave treatment. AB - Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed. In this study, employing microwave technology as a new means to improve solubility, we established a method for preparing solid dispersions using hydroxypropyl methylcellulose acetate succinate as a polymeric carrier and urea as a third component. This effective method has a treatment time of several minutes (simple) and does not require the use of organic solvents (low environmental impact). The third component, urea, acts to lower the melting point of NZ-105, which promotes amorphization. This greatly improves the solubility compared with the microwave-treated product of NZ-105/HPMC-AS binary system. The solid dispersion prepared with this method, in addition to evaluation in vitro, was tested in vivo using beagle dogs and shown to be effective from the eightfold improvement in absorption compared with NZ-105 alone based on the area under the curve. PMID- 27553262 TI - PLGA nanoparticles for peroral delivery: How important is pancreatic digestion and can we control it? AB - Biodegradable nanoparticles made of Poly(lactide-co-glycolide) are increasingly proposed for the improvement of oral drug absorption, but also as carriers for the treatment of colonic diseases. Unfortunately, our knowledge of the digestibility of PLGA-NPs is rather limited. Therefore, we investigated the impact of pancreatin on the digestibility of PLGA-NPs stabilized with different emulsifiers. The pancreatin induced degradation was monitored by the pH-stat method and an enzymatic l-lactic acid assay. A high digestibility was found for poloxamer 188 and polysorbate 80 stabilized PLGA-NPs. The digestion could be blocked by Orlistat, indicating a major role of pancreatic lipase. PLGA-NPs stabilized with Poly(vinyl alcohol) (=PVA) were not digested at comparable surfactant concentrations (0.6%). However, PLGA-NPs stabilized with very low amounts of PVA (0.1%) were digestible. In conclusion, PLGA-NPs are substrates for the pancreatic lipase. The digestibility can be enhanced or blocked by the proper selection of the surfactant composition and concentration. PMID- 27553263 TI - Film-forming formulations containing porous silica for the sustained delivery of actives to the skin. AB - The purpose of this study was to develop film-forming formulations facilitating long-term treatment of chronic pruritus with capsaicinoids. To this end, an oily solution of nonivamide was loaded into porous silica particles which were then suspended in the dispersion of a sustained release polymer. Such formulations form a film when applied to the skin and encapsulate the drug loaded silica particles in a dry polymeric matrix. Dermal delivery and permeation of the antipruritic drug nonivamide (NVA) are controlled by the matrix. The film-forming formulations were examined regarding homogeneity, storage stability, substantivity and ex vivo skin permeation. Confocal Raman spectral imaging proved the stability of silica-based film-forming formulations over a period of 6 months. Substantivity was found to be enhanced substantially compared to a conventional semisolid formulation. Permeation rates of nonivamide from film forming formulations through the skin are much lower compared to those achieved with a conventional immediate release formulation with the same drug amount. Due to the drug reservoir in the polymer matrix, a sustained permeation is enabled. Film-forming formulations may therefore improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance through a sustained release regime. PMID- 27553266 TI - Mid- and long-term results of femoral component revision using the cement-in cement technique: Average 10.8-year follow-up study. AB - BACKGROUND: Few reports are available on the long-term outcomes of femoral component revision by using the cement-in-cement technique. We report the mid- and long-term results of femoral component revision in total hip arthroplasty using the cement-in-cement technique. METHODS: Between April 1996 and June 2009, 62 consecutive total hip arthroplasties with femoral component revision were performed in 57 patients by using the cement-in-cement technique. We retrospectively reviewed the cases with a follow-up period of at least five years. Three patients died, and two were lost to follow-up. Thus, 52 patients (57 hips), comprising 51 women and one man, were followed for average 10.8 years. RESULTS: The mean Japanese Orthopaedic Association hip score improved from 57.6 points (range, 28-95 points) preoperatively to 79.8 points (range, 52-98 points) at one year postoperatively and to 77.4 points (range, 59-96 points) at the final follow up. Three revisions of the femoral component were necessary. One of the causes for the revision was a periprosthetic infection that occurred 20 months postoperatively. Another was aseptic loosening that occurred 99 months postoperatively and required revision of the acetabular component. The well-fixed femoral component was revised using the cement-in-cement technique at time of the acetabular revision. The third case was aseptic loosening of the femoral component that occurred 84 months postoperatively. The five-, 10-, and 15-year survival rates for the femoral re-revision due to any reason were 98.4%, 94.0%, and 94.0%, respectively. CONCLUSION: Use of the cement-in-cement technique for revision total hip arthroplasty resulted in good mid- and long-term radiological and clinical outcomes. PMID- 27553267 TI - The role of left and right dorsolateral prefrontal cortex in semantic processing: A transcranial direct current stimulation study. AB - For complex linguistic strings such as idioms, making a decision as to the correct meaning may require complex top-down cognitive control such as the suppression of incorrect alternative meanings. In the study presented here, we used transcranial direct current stimulation to test the hypothesis that a domain general dorsolateral prefrontal cognitive control network is involved in constraining the complex processing involved. Specifically, we sought to test prominent theoretical stances on the division of labour across dorsolateral prefrontal cortex in the left- and right-hemispheres of the brain, including the role of salience and fine vs. coarse semantic coding. 32 healthy young adult participants were randomly allocated to one of two stimulation montage groups (LH anodal/RH cathodal or RH anodal/LH cathodal). Participants were tested twice, completing a semantic decision task after either receiving active or sham stimulation. The semantic decision task required participants to judge the relatedness of an idiom and a target word. The target word was figuratively related, literally related, or unrelated to the idiom. Control non-literal non idiomatic sentences were also included that only had a literal meaning. The results showed that left-hemisphere dorsolateral prefrontal cortex is highly involved in processing figurative language, whereas both left- and right- dorsolateral prefrontal cortex contributed to literal language processing. In comparison, semantic processing for the non-idiomatic control sentences did not require domain general cognitive control as it relates to suppression of the rejected alternative meaning. The results are discussed in terms of the interplay between need for domain general cognitive control in understanding the meaning of complex sentences, hemispheric differences in semantic processing, and salience detection. PMID- 27553264 TI - Endocrine-disrupting chemicals and uterine fibroids. AB - Uterine fibroids are the most frequent gynecologic tumor, affecting 70% to 80% of women over their lifetime. Although these tumors are benign, they can cause significant morbidity and may require invasive treatments such as myomectomy and hysterectomy. Many risk factors for these tumors have been identified, including environmental exposures to endocrine-disrupting chemicals (EDCs) such as genistein and diethylstilbestrol. Uterine development may be a particularly sensitive window to environmental exposures, as some perinatal EDC exposures have been shown to increase tumorigenesis in both rodent models and human epidemiologic studies. The mechanisms by which EDC exposures may increase tumorigenesis are still being elucidated, but epigenetic reprogramming of the developing uterus is an emerging hypothesis. Given the remarkably high incidence of uterine fibroids and their significant impact on women's health, understanding more about how prenatal exposures to EDCs (and other environmental agents) may increase fibroid risk could be key to developing prevention and treatment strategies in the future. PMID- 27553268 TI - Behavioral characterization of prediction and internal models in adolescents with autistic spectrum disorders. AB - Autism has been considered as a deficit in prediction of the upcoming event or of the sensory consequences of our own movements. To test this hypothesis, we recorded eye movements from high-functioning autistic adolescents and from age matched controls during a blanking paradigm. In this paradigm, adolescents were instructed to follow a moving target with their eyes even during its transient disappearance. Given the absence of visual information during the blanking period, eye movements during this period are solely controlled on the basis of the prediction of the ongoing target motion. Typical markers of predictive eye movements such as the number and accuracy of predictive saccades and the predictive reacceleration before target reappearance were identical in the two populations. In addition, the synergy of predictive saccades and smooth pursuit observed during the blanking periods, which is a marker for the quality of internal models about target/eye motions, was comparable between these two populations. These results suggest that, in our large population of high functioning autistic adolescent, both predictive abilities and internal models are left intact in Autism, at least for low-level sensorimotor transformations. PMID- 27553269 TI - Both vision-for-perception and vision-for-action follow Weber's law at small object sizes, but violate it at larger sizes. AB - According to a previous report, the visual coding of size does not obey Weber's law when aimed at guiding a grasp (Ganel et al., 2008a). This result has been interpreted as evidence for a fundamental difference between sensory processing in vision-for-perception, which needs to compress a wide range of physical objects to a restricted range of percepts, and vision-for-action when applied to the much narrower range of graspable and reachable objects. We compared finger aperture in a motor task (precision grip) and perceptual task (cross modal matching or "manual estimation" of the object's size). Crucially, we tested the whole range of graspable objects. We report that both grips and estimations clearly violate Weber's law with medium-to-large objects, but are essentially consistent with Weber's law with smaller objects. These results differ from previous characterizations of perception-action dissociations in the precision of representations of object size. Implications for current functional interpretations of the dorsal and ventral processing streams in the human visual system are discussed. PMID- 27553265 TI - Evaluation of the fossil fish-specific diversity in a chadian continental assemblage: Exploration of morphological continuous variation in Synodontis (Ostariophysi, Siluriformes). AB - In the fossil record, the quantification of continuous morphological variation has become a central issue when dealing with species identification and speciation. In this context, fossil taxa with living representatives hold great promise, because of the potential to characterise patterns of intraspecific morphological variation in extant species prior to any interpretation in the fossil record. The vast majority of catfish families fulfil this prerequisite, as most of them are represented by extant genera. However, although they constitute a major fish group in terms of distribution, and ecological and taxonomic diversity, the quantitative study of their past morphological variation has been neglected, as fossil specimens are generally identified based on the scarcest remains, that is, complete neurocrania that bear discrete characters. Consequently, a part of freshwater catfish history is unprospected and unknown. In this study, we explored the morphological continuous variation of the humeral plate shape in Synodontis catfishes using Elliptic Fourier Analysis (EFA), and compared extant members and fossil counterparts. We analysed 153 extant specimens of 11 Synodontis species present in the Chad basin, in addition to 23 fossil specimens from the Chadian fossiliferous area of Toros Menalla which is dated around 7 Ma. This highly speciose genus, which is one of the most diversified in Africa, exhibits a rich fossil record with several hundred remains mostly identified as Synodontis sp. The analysis of the outline of the humeral plate reveals that some living morphological types were already represented in the Chad Basin 7 My ago, and allows for the discovery of extinct species. Beside illuminating the complex Neogene evolutionary history of Synodontis, these results underline the interest in the ability of isolated remains to reconstruct a past dynamic history and to validate the relevance of EFA as a tool to explore specific diversity through time. J. Morphol. 277:1486-1496, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27553270 TI - Social responsiveness to inanimate entities: Altered white matter in a 'social synaesthesia'. AB - Judgments about personalities and social traits can be made by relatively brief exposure to animate living things. Here we show that unusual architecture in the microstructure of the human brain is related to atypical mental projections of personality and social structure onto things that are neither living nor animate. Our participants experience automatic, life-long and consistent crossmodal associations between language sequences (e.g., letters, numbers and days) and complex personifications (e.g., A is a businessman; 7 a good-natured woman). Participants with this 'Ordinal Linguistic Personification' (Simner and Hubbard, 2006) which we describe here as a form of social synaesthesia, showed lower fractional anisotropy (FA) values in five clusters at whole-brain significance, compared with non-synaesthetes (in the pre-postcentral gyrus/dorsal corticospinal tract, left superior corona radiata, and the genu, body and left side of the corpus callosum). We found no regions of the brain with increased FA in synaesthetes. A number of these regions with reduced FA play a role in social responsiveness, and our study is the first to show that unusual differences in white matter microstructure in these regions is associated with compelling feelings of social cohesion and personality towards non-animate entities. We show too that altered patterns of connectivity known to typify synaesthesia are not limited to variants involving a 'merging of the senses', but also extend to what might be thought of as a cogno-social variant of synaesthesia, linking language and personality attributes in this surprising way. PMID- 27553271 TI - Mouse fibroblasts null for the long isoform of beta1,4-galactosyltransferase-I show defective cell-matrix interactions. AB - beta1,4 Galactosyltransferase-I (GalT-I) is expressed as two nearly identical polypeptides that differ only in the length of their cytoplasmic domains. The longer isoform has been implicated as a cell surface receptor for extracellular glycoside ligands, such as laminin. To more stringently test the function of the long GalT-I isoform during cell interactions with laminin, we created multiple independent fibroblastic cell lines that fail to express the long isoform, but which express the short GalT-I isoform normally and appear to have normal intracellular galactosylation. Cells devoid of the long GalT-I isoform are unable to adhere and spread on laminin substrates as well as control cells, but retain near normal interactions with fibronectin, which do not rely upon surface GalT-I function. The loss of the long GalT-I isoform also leads to a loss of actin stress fibers, focal adhesions and rac GTPase activation. PMID- 27553272 TI - Soybean Golgi SNARE 12 protein interacts with Soybean mosaic virus encoded P3N PIPO protein. AB - Soybean mosaic virus (SMV), a member of the Potyvirus genus, is one of the most prevalent and devastating viral pathogens in soybean-growing regions worldwide. It is generally accepted that symptom development of a viral plant disease results from molecular interactions between the virus and its host plant. P3N PIPO, as a trans-frame protein consisting of the amino-terminal half of P3 fused to PIPO of the Potyvirus, plays a key role of viral cell-to-cell movement. This study provides evidence that Golgi SNARE 12 (designated as GOS12) protein of soybean interacts with SMV P3N-PIPO via a two-hybrid yeast system by screening a soybean cDNA library. Bimolecular fluorescence complementation (BiFC) assay further confirmed the interaction, which occurred in the cytomembrane of Nicotiana benthamiana cells. We also confirmed that the domain involved in the interaction is PIPO domain of P3N-PIPO by two-hybrid yeast system and BiFC. It is possible that the GOS12 is an essential host factor for PD targeting of P3N-PIPO protein of potyvirus. PMID- 27553273 TI - Influence of alphavbeta3 integrin on the mechanical properties and the morphology of M21 and K562 cells. AB - Integrins play an important role in cell adhesion, morphology, migration, and many other physiological processes. The role of alphavbeta3 integrin has been intensively investigated in the past. However, much is still unclear about its selective role in cell contractility, adhesion, and mechanics. We looked at the influence of alphavbeta3 integrin on the cell mechanics of adherent M21 and suspended K562 cells with a microconstriction assay and found that the expression of alphavbeta3 integrin leads to higher cell stiffness and decreased fluidity in both cell lines. The disruption of the actin cytoskeleton decreased cellular stiffness in M21 (expressing alpha5beta1 and alphavbeta3 integrins) and M21L (expressing only alpha5beta1 integrin) cell lines in a similar way, but did not lead to the same baseline stiffness. The activation of integrins after the addition of Mn(2+) led to higher stiffness in all observed cell lines, independent of alphavbeta3 integrin expression and disruption of the actin cytoskeleton. In summary, these results show that differences in stiffness/fluidity due to alphavbeta3 integrin expression or integrin activation by Mn(2+) might not simply be explained by the coupling of integrins to actin via focal adhesions, which in turn induces changes in the actin cytoskeleton, but also by other cellular components such as the cell nucleus, intermediate filaments, or microtubules. PMID- 27553274 TI - Gallus gallus orthologous to human alpha-dystroglycanopathies candidate genes: Gene expression and characterization during chicken embryogenesis. AB - Alpha-dystroglycanopathies are a heterogenic group of human rare diseases that have in common defects of alpha-dystroglycan O-glycosylation. These congenital disorders share common features as muscular dystrophy, malformations on central nervous system and more rarely altered ocular development, as well as mutations on a set of candidate genes involved on those syndromes. Severity of the syndromes is variable, appearing Walker-Warburg as the most severe where mutations at protein O-mannosyl transferases POMT1 and POMT2 genes are frequently described. When studying the lack of MmPomt1 in mouse embryonic development, as a murine model of Walker-Warburg syndrome, MmPomt1 null phenotype was lethal because Reitchert's membrane fails during embryonic development. Here, we report gene expression from Gallus gallus orthologous genes to human candidates on alpha dystroglycanopathies POMT1, POMT2, POMGnT1, FKTN, FKRP and LARGE, making special emphasis in expression and localization of GgPomt1. Results obtained by quantitative RT-PCR, western-blot and immunochemistry revealed close gene expression patterns among human and chicken at key tissues affected during development when suffering an alpha-dystroglycanopathy, leading us to stand chicken as a useful animal model for molecular characterization of glycosyltransferases involved in the O-glycosylation of alpha-Dystroglycan and its role in embryonic development. PMID- 27553275 TI - Structural basis for multi-specific peptide recognition by the anti-IDH1/2 monoclonal antibody, MsMab-1. AB - A point mutation in isocitrate dehydrogenase 1 (IDH1) and IDH2 is directly linked to the pathogenesis of certain types of tumors. To detect this mutation, several antibodies that can distinguish between mutant and wild-type enzymes have been established. One of which, MsMab-1, has a unique multi-specific character against several types of mutated IDH1/2. This promiscuous character is in remarkable contrast to the highly specific antigen recognition typically observed with a monoclonal antibody. We solved the crystal structure of MsMab-1 Fab fragment in complex with either IDH1 or IDH2-derived peptides. Based on the structure, it became clear that the peptide-binding pocket of the antibody is highly complementary to the core determinant shared between the IDH1 and IDH2, while leaving just enough space for the side chain of the pathogenic but not the wild type amino acids located in the mutation position. Clarification of the molecular basis for the peculiar binding characteristics of MsMab-1 in atomic detail will help facilitating its diagnostic application, and may be used to develop better diagnostic reagents through structure-guided protein engineering. PMID- 27553277 TI - Cysteinome: The first comprehensive database for proteins with targetable cysteine and their covalent inhibitors. AB - The covalent modification of intrinsically nucleophilic cysteine in proteins is crucial for diverse biochemical events. Bioinformatics approaches may prove useful in the design and discovery of covalent molecules targeting the cysteine in proteins to tune their functions and activities. Herein, we describe the Cysteinome, the first online database that provides a rich resource for the display, search and analysis of structure, function and related annotation for proteins with targetable cysteine as well as their covalent modulators. To this end, Cysteinome compiles 462 proteins with targetable cysteine from 122 different species along with 1217 covalent modulators curated from existing literatures. Proteins are annotated with a detailed description of protein families, biological process and related diseases. In addition, covalent modulators are carefully annotated with chemical name, chemical structure, binding affinity, physicochemical properties, molecule type and related diseases etc. The Cysteinome database may serve as a useful platform for the identification of crucial proteins with targetable cysteine in certain cellular context. Furthermore, it may help biologists and chemists for the design and discovery of covalent chemical probes or inhibitors homing at functional cysteine of critical protein targets implicated in various physiological or disease process. The Cysteinome database is freely available to public at http://www.cysteinome.org/. PMID- 27553278 TI - Selective killing of cancer cells by small molecules targeting heat shock stress response. AB - HSF1 heat shock response has emerged as a valuable non-oncogenetic intervention point in targeted cancer therapy. Current reporter based high throughput screening has led to the discovery of several compounds or chemotypes that are effective in the growth inhibition of multiple cancer cell lines and relevant animal tumor models. However, some intrinsic limitations of reporter based assays can potentially lead to biased results. Using a previously validated high content image based assay, we performed a phenotypic screen targeting HSF1 heat shock pathway with a chemically diversified library of over 100,000 compounds. Several novel functional inhibitors of HSF1 pathway were identified with different chemotypes. Western blot analysis confirmed that selective compounds inhibit phosphorylation of HSF1, followed by reduced expression of HSP proteins. Moreover, HeLa cells stably transfected with HSF1 shRNA were more resistant to the compound treatment under lethal temperature than cells containing HSF1, validating HSF1 dependent mechanism of action. These compounds demonstrate nanomolar potency toward multiple cancer cell lines with relatively low cytotoxicity to normal cells. Further SAR and target identification study will pave the way for the potential development of next generation anticancer drugs. PMID- 27553276 TI - Calcium's role as nuanced modulator of cellular physiology in the brain. AB - Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer's disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely, can alter neuronal communication and synaptic strength in positive ways, without necessarily killing neurons. Here, we focus on the evidence that calcium has a subtle and distinctive role in shaping and controlling synaptic events that underpin neuronal communication and that these subtle changes in aging or AD may contribute to cognitive decline. We emphasize that calcium imaging in dendritic components is ultimately necessary to directly test for the presence of age- or disease-associated alterations during periods of synaptic activation. PMID- 27553279 TI - Cellular response to high pulse repetition rate nanosecond pulses varies with fluorescent marker identity. AB - Nanosecond electric pulses (nsEP's) are a well-studied phenomena in biophysics that cause substantial alterations to cellular membrane dynamics, internal biochemistry, and cytoskeletal structure, and induce apoptotic and necrotic cell death. While several studies have attempted to measure the effects of multiple nanosecond pulses, the effect of pulse repetition rate (PRR) has received little attention, especially at frequencies greater than 100 Hz. In this study, uptake of Propidium Iodide, FM 1-43, and YO-PRO-1 fluorescent dyes in CHO-K1 cells was monitored across a wide range of PRRs (5 Hz-500 KHz) using a laser-scanning confocal microscope in order to better understand how high frequency repetition rates impact induced biophysical changes. We show that frequency trends depend on the identity of the dye under study, which could implicate transmembrane protein channels in the uptake response due to their chemical selectivity. Finally, YO PRO-1 fluorescence was monitored in the presence of Gadolinium (Gd(3+)), Ruthenium Red, and in calcium-free solution to elucidate a mechanism for its unique frequency trend. PMID- 27553280 TI - The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy. AB - The majority of studies on possible roles for collagen hydrolysates in human health have focused on their effects on bone and skin. Hydroxyprolyl-glycine (Hyp Gly) was recently identified as a novel collagen hydrolysate-derived dipeptide in human blood. However, any possible health benefits of Hyp-Gly remain unclear. Here, we report the effects of Hyp-Gly on differentiation and hypertrophy of murine skeletal muscle C2C12 cells. Hyp-Gly increased the fusion index, the myotube size, and the expression of the myotube-specific myosin heavy chain (MyHC) and tropomyosin structural proteins. Hyp-Gly increased the phosphorylation of Akt, mTOR, and p70S6K in myoblasts, whereas the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibited their phosphorylation by Hyp-Gly. LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin repressed the enhancing effects of Hyp-Gly on MyHC and tropomyosin expression. The peptide/histidine transporter 1 (PHT1) was highly expressed in both myoblasts and myotubes, and co-administration of histidine inhibited Hyp-Gly-induced phosphorylation of p70S6K in myoblasts and myotubes. These results indicate that Hyp-Gly can induce myogenic differentiation and myotube hypertrophy and suggest that Hyp-Gly promotes myogenic differentiation by activating the PI3K/Akt/mTOR signaling pathway, perhaps depending on PHT1 for entry into cells. PMID- 27553281 TI - Synchrotron FTIR microspectroscopy reveals early adipogenic differentiation of human mesenchymal stem cells at single-cell level. AB - Human mesenchymal stem cells (hMSCs) have been used as an ideal in vitro model to study human adipogenesis. However, little knowledge of the early stage differentiation greatly hinders our understanding on the mechanism of the adipogenesis processes. In this study, synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy was applied to track the global structural and compositional changes of lipids, proteins and nucleic acids inside individual hMSCs along the time course. The multivariate analysis of the SR-FTIR spectra distinguished the dynamic and significant changes of the lipids and nucleic acid at early differentiation stage. Importantly, changes of lipid structure during early days (Day 1-3) of differentiation might serve as a potential biomarker in identifying the state in early differentiation at single cell level. These results proved that SR-FTIR is a powerful tool to study the stem cell fate determination and early lipogenesis events. PMID- 27553282 TI - CD27(-)CD45(+) gammadelta T cells can be divided into two populations, CD27( )CD45(int) and CD27(-)CD45(hi) with little proliferation potential. AB - In addition to the majority of T cells which carry the alphabeta T cell receptor (TCR) for antigen, a distinct subset of about 1-5% of human peripheral blood T cells expressing the gammadelta TCR contributes to immune responses to infection, tissue damage and cancer. T cells with the Vdelta2(+) TCR, usually paired with Vgamma9, constitute the majority of these gammadelta T cells. Analogous to alphabeta T cells, they can be sorted into naive (CD27(+)CD45RA(+)), central memory (CD27(+)CD45RA(-)), effector memory (CD27(-)CD45RA(-)), and terminally differentiated effector memory (CD27(-)CD45RA(+)) phenotypes. Here, we found that CD27(-)CD45RA(+) gammadelta T cells can be further divided into two populations based on the level of expression of CD45RA: CD27(-)CD45RA(int) and CD27( )CD45RA(hi). Those with the CD27(-)CD45RA(hi) phenotype lack extensive proliferative capacity, while those with the CD27(-)CD45RA(int) phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27(-)CD45RA(hi) potentially exhausted gammadelta T cells were found predominantly in cancer patients but also in healthy subjects. We conclude that gammadelta T cells can be divided into at least 5 subsets enabling discrimination of gammadelta T cells with poor proliferative capacity. It was one of our goals to predict the feasibility of gammadelta T cell expansion to sufficient amounts for adoptive immunotherapy without the necessity for conducting small-scale culture tests. Fulfilling the >=1.5% criterion for gammadelta T cells with phenotypes other than CD27(-)CD45RA(hi), may help avoid small-scale culture testing and shorten the preparation period for adoptive gammadelta T cells by 10 days, which may be beneficial for patients with advanced cancer. PMID- 27553283 TI - A long-lasting cardiomyogenic gene expression by PEI-based transfection induces endogenous cardiac mRNAs in human adipose-derived stem cells. AB - Our previous work revealed that a polyethyleneimine (PEI)-based gene delivery causes robust and sustained expression of exogenous genes in human adipose derived stem cells (hADSCs). Here we use this method to test whether a single introduction of cDNAs for the three cardiomyogenic reprogramming genes (GATA4, MEF2C, and TBX5) might be sufficient to induce transdifferentiation of hADSCs towards the cardiomyogenic lineage. A single transfection results in sustained expression of the introduced genes for more than two weeks. hADSCs exhibit undetectable or very low levels of mRNAs for endogenous GATA4, MEF2C and TBX5. However, mRNAs for these endogenous factors become apparent at ~2 weeks after transfection and keep increasing until the end of experimental period at the fifth week. Concordant with these cardiomyogenic genes, Nkx2.5 mRNA becomes significant at ~2 weeks and gradually increases until the end of experimental period. Several other cardiomyogenic mRNAs were also significant at 5 weeks. Thus, a single transfection of cDNAs for the cardiomyogenic reprogramming genes using a PEI-based method induces transdifferentiation of ADSCs. PMID- 27553284 TI - Tetrahydrocarbazoles decrease elevated SOCE in medium spiny neurons from transgenic YAC128 mice, a model of Huntington's disease. AB - Huntington's disease (HD) is a hereditary neurodegenerative disease caused by a polyglutamine expansion within the huntingtin (HTT) gene. One of the cellular functions that is dysregulated in HD is store-operated calcium entry (SOCE), a process in which the depletion of Ca2+ from the endoplasmic reticulum (ER) induces Ca2+ influx from the extracellular space. We detected an enhanced activity of SOC channels in medium spiny neurons (MSNs) from YAC128 mice, a transgenic model of HD, and investigated whether this could be reverted by tetrahydrocarbazoles. The compound 6-bromo-N-(2-phenylethyl)-2,3,4,9-tetrahydro 1H-carbazol-1-amine hydrochloride was indeed able to restore the disturbed Ca2+ homeostasis and stabilize SOCE in YAC128 MSN cultures. We also detected a beneficial effect of this compound on the mitochondrial membrane potential. Since dysregulated Ca2+ homeostasis is believed to be one of the pathological hallmarks of HD, this compound might be a lead structure for HD treatment. PMID- 27553285 TI - Decreased cruzipain and gp85/trans-sialidase family protein expression contributes to loss of Trypanosoma cruzi trypomastigote virulence. AB - Two cell lines derived from a single Trypanosoma cruzi clone by long-term passaging generated a highly virulent (C8C3hvir) and a low virulent (C8C3lvir) cell line. The C8C3hvir cell line was highly infective and lethal to Balb/c mice, and the C8C3lvir cell line was three- to five-fold less infective to mouse cardiomyocytes than C8C3hvir. The highly virulent T. cruzi cell line abundantly expressed the major cysteine proteinase cruzipain (Czp), complement regulatory protein (CRP) and trans-sialidase (TS), all of which are known to act as virulence factors in this parasite. The in vitro invasion capacity and in vivo Balb/c mouse infectiveness of the highly virulent strain was strongly reduced by pre-treatment with antisense oligonucleotides targeting TS or CRP or with E64d. Based on these results, we conclude that decreased levels of TS, CRP and Czp expression could contribute to loss of T. cruzi trypomastigote virulence. PMID- 27553286 TI - HIV and Heart Disease: What Cardiologists Should Know. PMID- 27553288 TI - Manifest and Concealed Atrioventricular Nodal Double Firing. PMID- 27553287 TI - Burden of Heart Failure in Latin America: A Systematic Review and Meta-analysis. AB - INTRODUCTION AND OBJECTIVES: Heart failure is a major public health concern. The aim of this review was to estimate the burden of heart failure in Latin America. METHODS: Systematic review and meta-analysis following a search in MEDLINE, EMBASE, LILACS, and CENTRAL for articles published between January 1994 and June 2014, with no language restrictions. We included experimental and observational studies with at least 50 participants aged >= 18 years. RESULTS: In total, 143 of the 4792 references retrieved were included in the study. Most studies had been conducted in South America (92%), and mainly in Brazil (64%). The mean age of the patients was 60 +/- 9 years, and mean ejection fraction was 36% +/- 9%. The incidence of heart failure in the single population study providing this information was 199 cases per 100000 person-years. The prevalence of heart failure was 1% (95% confidence interval [95%CI], 0.1%-2.7%); hospital readmission rates were 33%, 28%, 31%, and 35% at 3, 6, 12, and 24 to 60 months of follow-up, respectively; and the median duration of hospitalization was 7.0 days. The 1-year mortality rate was 24.5% (95%CI, 19.4%-30.0%). In-hospital mortality was 11.7% (95%CI, 10.4%-13.0%), and the rate was higher in patients with a reduced ejection fraction, ischemic heart disease, or Chagas disease. CONCLUSIONS: Few studies have evaluated the incidence and prevalence of heart failure in Latin America. High mortality and hospitalization rates were found, and the main limitation was heterogeneity between studies. The results presented provide useful epidemiologic information for decision-making related to this disease. Further studies with standardized methods and representative populations are needed in this line. PMID- 27553289 TI - Coronary Artery Atherosclerosis in Hypertensive Patients: The Role of Fibrinogen Genetic Variability. AB - INTRODUCTION AND OBJECTIVES: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. METHODS: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. RESULTS: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (beta = 0.257 +/- 18.6; P<.001), but not hypertension status (beta = 0.05 +/- 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (beta = 0.151 +/- 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). CONCLUSIONS: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients. PMID- 27553290 TI - Enhanced Capacitance of Hybrid Layered Graphene/Nickel Nanocomposite for Supercapacitors. AB - In this work, Ni nanoparticles were directly decorated on graphene (G) nanosheets via mechanical ball milling. Based on transmission electron microscopy observations, the Ni nanoparticles were well dispersed and attached to the G nanosheet without any agglomerations. Electrochemical results showed that the capacitance of a G/Ni nanocomposite was 275 F g(-1) at a current density of 2 A g(-1), which is higher than the capacitance of bare G (145 F g(-1)) and bare Ni (3 F g(-1)). The G/Ni electrode also showed superior performance at a high current density, exhibiting a capacitance of 190 F g(-1) at a current density of 5 A g(-1) and a capacitance of 144 F g(-1) at a current density of 10 A g(-1). The equivalent series resistance for G/Ni nanocomposites also decreased. The enhanced performance of this hybrid supercapacitor is best described by the synergistic effect, i.e. dual charge-storage mechanism, which is demonstrated by electrical double layer and pseudocapacitance materials. Moreover, a high specific surface area and electrical conductivity of the materials enhanced the capacitance. These results indicate that the G/Ni nanocomposite is a potential supercapacitor. PMID- 27553292 TI - Joint research projects will focus on social impact of Zika in Brazil. PMID- 27553291 TI - High prevalence and predominance of BRCA1 germline mutations in Pakistani triple negative breast cancer patients. AB - BACKGROUND: Women harboring BRCA1/2 germline mutations have high lifetime risk of developing breast/ovarian cancer. The recommendation to pursue BRCA1/2 testing is based on patient's family history of breast/ovarian cancer, age of disease-onset and/or pathologic parameters of breast tumors. Here, we investigated if diagnosis of triple-negative breast cancer (TNBC) independently increases risk of carrying a BRCA1/2 mutation in Pakistan. METHODS: Five hundred and twenty-three breast cancer patients including 237 diagnosed <= 30 years of age and 286 with a family history of breast/ovarian cancer were screened for BRCA1/2 small-range mutations and large genomic rearrangements. Immunohistochemical analyses were performed at one center. Univariate and multiple logistic regression models were used to investigate possible differences in prevalence of BRCA1/2 mutations according to patient and tumor characteristics. RESULTS: Thirty-seven percent of patients presented with TNBC. The prevalence of BRCA1 mutations was higher in patients with TNBC than non-TNBC (37 % vs. 10 %, P < 0.0001). 1 % of TNBC patients were observed to have BRCA2 mutations. Subgroup analyses revealed a larger proportion of BRCA1 mutations in TNBC than non-TNBC among patients 1) diagnosed at early-age with no family history of breast/ovarian cancer (14 % vs. 5 %, P = 0.03), 2) diagnosed at early-age irrespective of family history (28 % vs. 11 %, P = 0.0003), 3) had a family history of breast cancer (49 % vs. 12 %, P < 0.0001), and 4) those with family history of breast and ovarian cancer (81 % vs. 28 %, P = 0.0005). TNBC patients harboring BRCA1 mutations were diagnosed at a later age than non-carriers (median age at diagnosis: 30 years (range 22-53) vs. 28 years (range 18-67), P = 0.002). The association between TNBC status and presence of BRCA1 mutations was independent of the simultaneous consideration of family phenotype, tumor histology and grade in a multiple logistic regression model (Ratio of the probability of carrying BRCA1/2 mutations for TNBC vs. non-TNBC 4.23; 95 % CI 2.50-7.14; P < 0.0001). CONCLUSION: Genetic BRCA1 testing should be considered for Pakistani women diagnosed with TNBC. PMID- 27553293 TI - Preclinical PET Neuroimaging of [11C]Bexarotene. AB - Activation of retinoid X receptors (RXRs) has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [(11)C]CO2 fixation and preliminary positron emission tomography (PET) neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [(11)C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions. [(11)C]Bexarotene displays a high proportion of nonsaturable uptake in the brain and is unsuitable for RXR occupancy measurements in the central nervous system. PMID- 27553294 TI - A Blocking Group Scan Using a Spherical Organometallic Complex Identifies an Unprecedented Binding Mode with Potent Activity In Vitro and In Vivo for the Opioid Peptide Dermorphin. AB - Herein, the selective enforcement of one particular receptor-ligand interaction between specific domains of the MU-selective opioid peptide dermorphin and the MU opioid receptor is presented. For this, a blocking group scan is described which exploits the steric demand of a bis(quinolinylmethyl)amine rhenium(I) tricarbonyl complex conjugated to a number of different, strategically chosen positions of dermorphin. The prepared peptide conjugates lead to the discovery of two different binding modes: An expected N-terminal binding mode corresponds to the established view of opioid peptide binding, whereas an unexpected C-terminal binding mode is newly discovered. Surprisingly, both binding modes provide high affinity and agonistic activity at the MU opioid receptor in vitro. Furthermore, the unprecedented C-terminal binding mode shows potent dose-dependent antinociception in vivo. Finally, in silico docking studies support receptor activation by both dermorphin binding modes and suggest a biological relevance for dermorphin itself. Relevant ligand-protein interactions are similar for both binding modes, which is in line with previous protein mutation studies. PMID- 27553295 TI - Analysis of 58 Families of Holins Using a Novel Program, PhyST. AB - We have designed a freely accessible program, PhyST, which allows the automated characterization of any family of homologous proteins within the Transporter Classification Database. The program performs an NCBI-PSI-BLAST search and reports (1) the average protein sequence length with standard deviations, (2) the average predicted number of transmembrane segments, (3) the total number of homologues retrieved, (4) a quantitative list of all source phyla, and (5) potential fusion proteins of sizes considerably exceeding the average size of the proteins retrieved. We have applied this program to 58 families of holins, and the results are presented. The results show that holins are very rarely fused to other protein domains, suggesting that holins form transmembrane pores as homooligomers without the participation of other proteins or protein domains. PMID- 27553296 TI - Metachronous pancreatic metastases from renal cell carcinoma: is there a place of Active-Surveillance before deferred deliberately Molecular Target Agent? AB - BACKGROUND: Metastatic renal cell cancer is a heterogeneous disease due to its diverse morphological features, the prognostic categories based on clinical criteria. Sometimes indolent course without any significant symptoms can be differentiated before the introduction of novel targeted agents. This observation led to interest in a strategy of deferring systemic therapy in the era of effective systemic therapies. CASE PRESENTATION: We report of a 78-year-old Moroccan man with pancreatic metastasis from renal cell carcinoma which occurred 14 years from right nephrectomy. Indolent disease based on body computed tomography imaging with 4 years follow-up was recognized. Active surveillance with deferred antiangiogenic multikinase inhibitor at disease progression was proposed. Nowadays, the patient is under oncological follow-up, he is in a good state of health, and he is disease-free for 48 months from the diagnosis of the tumor and for 20 months from the start of the treatment with Sunitinib CONCLUSIONS: Active surveillance before target therapy may be a suitable approach to ensure long progression-free survival with minimal side-effects and better quality of life in asymptomatic, low-volume, metastatic disease. Further prospective studies with biomarker validation are required to define the patients most likely to benefit from this approach. PMID- 27553297 TI - Factors affecting quadriceps strength recovery after anterior cruciate ligament reconstruction with hamstring autografts in athletes. AB - PURPOSE: Patients typically return to sports activities 6-12 months after anterior cruciate ligament (ACL) reconstruction, and quadriceps strength has been used as one of the criteria to return to sports activities. The purpose of this study is to identify the factors that affect quadriceps strength recovery after ACL reconstruction with a hamstring tendon autograft 6 months after surgery. METHODS: Isokinetic quadriceps strength at 60 degrees /s was measured preoperatively and 6 months after surgery in 193 athletes who underwent ACL reconstruction with a hamstring tendon autograft. The quadriceps strength index was calculated by normalizing the peak torque of the involved leg with the uninvolved leg. The subjects were divided into two groups according to the quadriceps strength index 6 months after surgery: at least 85 % (n = 84) or less than 85 % (n = 109). Multivariate logistic regression analysis and a receiver operating curve analysis were performed. RESULTS: The preoperative quadriceps strength index [odds ratio (OR) 1.02; 95 % confidence interval (CI) 1.01-1.03], age (OR 0.92; 95 % CI 0.86-0.98), sex (OR 2.45; 95 % CI 1.19-5.18), and knee pain (OR 0.17; 95 % CI 0.04-0.52) were independently associated with quadriceps strength recovery. The cut-off value of the preoperative quadriceps strength index was 70.2 % to obtain at least 85 % quadriceps strength index 6 months after surgery. CONCLUSION: To achieve sufficient quadriceps strength recovery at the timing of return to sports activities following ACL reconstruction using a hamstring tendon autograft, preoperative quadriceps strength, age, sex, and knee pain should be considered. LEVEL OF EVIDENCE: III. PMID- 27553298 TI - Comparison of outcome of ARIF and ORIF in the treatment of tibial plateau fractures. AB - PURPOSE: The purpose of this study is to explore whether arthroscopically assisted reduction and internal fixation (ARIF) is superior to traditional open reduction and internal fixation (ORIF) in the treatment of tibial plateau fractures. METHODS: Fifty-seven patients with tibial plateau fractures (Schatzker type I-IV) treated by ARIF or ORIF from 2010 to 2013 were included in this retrospective study. All patients received pre-operative radiographs and CT scans. The patients were divided into two groups (ARIF or ORIF). All had a minimum follow-up of 24 months and an average follow-up of 44.4 months. The clinical and radiographic outcomes were evaluated according to the Rasmussen and KSS scores. RESULTS: There was no significant difference in KSS score or Rasmussen clinical score between the two groups. The average Rasmussen radiographic score was 14.1 (SD 2.4, range 10-18), for the ARIF group and 14.9 (SD 2.3, range 10-18) for the ORIF group (p < 0.05). Meniscal lesions were found in 12 knees in group ARIF. CONCLUSIONS: Both ARIF and ORIF yielded satisfactory clinical results for the treatment of Schatzker I-IV tibial plateau fractures. ARIF led to better radiological results than ORIF. Concomitant intra-articular soft tissue lesions are common and can be addressed during ARIF. LEVEL OF EVIDENCE: III. PMID- 27553299 TI - Effects of instant controlled pressure drop process on physical and sensory properties of puffed wheat snack. AB - BACKGROUND: In this study, research on the development of a puffed wheat snack using the instant controlled pressure drop (DIC) process was carried out. Snack products were produced by expanding moistened wheat under various DIC processing conditions in order to obtain adequate puffing, followed by drying in a hot air dryer. The effects of operational variables such as wheat initial moisture content (11-23% w/w, wet basis), processing pressure (3-5 * 102 kPa) and processing time (3-11 min) on the physical (density, color and textural characteristics) and sensory properties of the product were investigated. RESULTS: The physical properties of the wheat snack were most affected by changes in processing pressure, followed by processing time and wheat moisture content. Increasing processing pressure and time often improved expansion and textural properties but led to darkening of the raw wheat color. The most acceptable snack in terms of physical properties was obtained at the lowest wheat moisture content. Sensory analysis suggested that consumer acceptability was optimal for wheat snacks produced at higher processing pressure, medium processing time and lower moisture content. CONCLUSION: The most desirable conditions for puffed wheat snack production using the DIC process were determined as 11% (w/w) of wheat moisture content, 5 * 102 kPa of processing pressure and 7 min of processing time. (c) 2016 Society of Chemical Industry. PMID- 27553300 TI - Common Infectious Organisms. AB - Cytology offers a rapid, relatively noninvasive means to identify lesions of all varieties including immune-mediated, degenerate, inflammatory, and neoplastic. One area that is particularly amenable to cytologic diagnosis is infectious disease. Organisms that can be seen and identified include fungal, bacterial, protozoal, parasitic, viral, and algal. Rapid identification of pathogenic organisms allows the practitioner to initiate treatment quickly, giving the patient the best chance for recovery. PMID- 27553301 TI - Dissipative particle dynamics simulations of the viscosities of molten TNT and molten TNT suspensions containing nanoparticles. AB - Based on dissipative particle dynamics (DPD) methods and experimental data, we used an empirical relationship between the DPD temperature and the real temperature to build a model that describes the viscosity of molten TNT fluids. The errors in the predicted viscosity based on this model were no more than 2.3 %. We also studied the steady-state shear rheological behavior of molten TNT fluids containing nanoparticles ("nanofluids"). The dependence of the nanofluid viscosity on the temperature was found to satisfy an Arrhenius-type equation, eta = Ae (B/T) , where B, the flow activation energy, depends on particle content, size, and shape. We modified the Einstein-type viscosity model to account for the effects of nanoparticle solvation in TNT nanofluids. The resulting model was able to correctly predict the viscosities of suspensions containing nano- to microsized particles, and did not require any changes to the physical background of Einstein's viscosity theory. Graphical Abstract The revised Einstein viscosity model that correctly predict the viscosity of TNT suspensions containing nanoparticles. PMID- 27553302 TI - Theoretical study of the interaction between molecular oxygen and tetraaza macrocyclic manganese complexes. AB - Theoretical chemistry calculations using the Density Functional Theory (DFT) were carried out to understand the interaction between oxygen (O2) and MnN4 type manganese-based complexes during the formation of MnN4-O2 adducts. In order to understand how this interaction is affected by different macrocyclic ligands, O2 was bonded to manganese-porphyrin (MnP), manganese-octamethylporphyrin (MnOMP), manganese-tetraaza[14]annulene (MnTAA), manganese-dibenzo [b,i] [1, 4, 8, 11] tetraaza [14] annulene (MnDBTAA), manganese-2,3,9,10-tetramethyl-1,4,8,11 tetraazacyclotetradeca-1,3,8,10-tetraene ([(tim)Mn](2+)), and manganese-2,3,9,10 tetraphenyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene ([(ph-tim)Mn](2+)). The binding and activation of the oxygen molecule was facilitated by an increasing trend in the O-O bond lengths and a decreasing one in the O-O vibrational frequency, with preference for the O2 side-on interaction among MnN4 macrocycles. The catalytic activities of the MnN4 complexes toward the O2 binding process increased in the following order: [(ph-tim)Mn](2+) < MnP < MnOMP < MnDBTAA < MnTAA < [(tim)Mn](2+). Therefore, it was concluded that the [(tim)Mn](2+)complex was the most active for the binding and activation of molecular oxygen. PMID- 27553303 TI - A Monte Carlo-quantum mechanics study of a solvatochromic pi* probe. AB - The solvation and the solvatochromic behavior of 5-(dimethylamino)-5'-nitro-2,2' bithiophene 1, the basis of a pi* scale of solvent polarities, was investigated theoretically in toluene, dichloromethane, methanol and formamide with a Monte Carlo and quantum mechanics (QM/MM) iterative approach. The calculated transition energies of the solvatochromic band of 1, obtained as averages of statistically uncorrelated configurations, including the solute and explicit solvent molecules of the first solvation layer, besides showing good agreement with the experimental transitions, reproduced very well the positive solvatochromism of this probe in various solvents. PMID- 27553305 TI - Giant mesenteric haemangioma presenting with severe anaemia. PMID- 27553304 TI - On the possibility to accelerate the thermal isomerizations of overcrowded alkene based rotary molecular motors with electron-donating or electron-withdrawing substituents. AB - We employ computational methods to investigate the possibility of using electron donating or electron-withdrawing substituents to reduce the free-energy barriers of the thermal isomerizations that limit the rotational frequencies achievable by synthetic overcrowded alkene-based molecular motors. Choosing as reference systems one of the fastest motors known to date and two variants thereof, we consider six new motors obtained by introducing electron-donating methoxy and dimethylamino or electron-withdrawing nitro and cyano substituents in conjugation with the central olefinic bond connecting the two (stator and rotator) motor halves. Performing density functional theory calculations, we then show that electron-donating (but not electron-withdrawing) groups at the stator are able to reduce the already small barriers of the reference motors by up to 18 kJ mol(-1). This result outlines a possible strategy for improving the rotational frequencies of motors of this kind. Furthermore, exploring the origin of the catalytic effect, it is found that electron-donating groups exert a favorable steric influence on the thermal isomerizations, which is not manifested by electron withdrawing groups. This finding suggests a new mechanism for controlling the critical steric interactions of these motors. Graphical Abstract The introduction of electron-donating groups in one of the fastest rotary molecular motors known to date is found to reduce the free-energy barriers of the thermal steps that limit the rotational frequencies by up to 18 kJ mol(-1). PMID- 27553346 TI - Intravascular ultrasound-guided retrograde percutaneous coronary intervention of a chronic total occlusion. PMID- 27553347 TI - Left ventricle rupture during percutaneous coronary intervention. PMID- 27553348 TI - The paramount importance of repeated left ventricular endomyocardial biopsy during the diagnosis of restrictive cardiomyopathy due to AL cardiac amyloidosis. PMID- 27553349 TI - Retinal artery occlusion as an announcement of stroke and myocardial infarction? PMID- 27553350 TI - Single persistent left superior vena cava compressed by an aortic graft on the route for lead insertion - difficulties in attempted pacemaker implantation. PMID- 27553351 TI - Reverse iatrogenic Takotsubo syndrome after accidental bolus of norepinephrine in the setting of sepsis. PMID- 27553352 TI - [Coordinated care after myocardial infarction. The statement of the Polish Cardiac Society and the Agency for Health Technology Assessment and Tariff System]. AB - The in-hospital mortality following myocardial infarction has decreased substantially over the last two decades in Poland. However, according to the available evidence approximately every 10th patient discharged after myocardial infarction (MI) dies during next 12 months. We identified the most important barriers (e.g. insufficient risk factors control, insufficient and delayed cardiac rehabilitation, suboptimal pharmacotherapy, delayed complete myocardial revascularisation) and proposed a new nation-wide system of coordinated care after MI. The system should consist of four modules: complete revascularisation, education and rehabilitation programme, electrotherapy (including ICDs and BiVs when appropriate) and periodical cardiac consultations. At first stage the coordinated care programme should last 12 months. The proposal contains also the quality of care assessment based on clinical measures (e.g. risk factors control, rate of complete myocardial revascularisation, etc.) as well as on the rate of cardiovascular events. The wide implementation of the proposed system is expected to decrease one year mortality after MI and allow for better financial resources allocation in Poland. PMID- 27553353 TI - [Electrocardiographic criteria for diagnosis of the heart chamber enlargement, necrosis and repolarisation abnormalities including acute coronary syndromes. Experts' group statement of the Working Group on Noninvasive Electrocardiology and Telemedicine of]. PMID- 27553354 TI - Pathologists and liquid biopsies: to be or not to be? AB - Recently, the advent of therapies targeting genomic alterations has improved the care of patients with certain types of cancer. While molecular targets were initially detected in nucleic acid samples extracted from tumor tissue, detection of nucleic acids in circulating blood has allowed the development of what has become known as liquid biopsies, which provide a complementary and alternative sample source allowing identification of genomic alterations that might be addressed by targeted therapy. Consequently, liquid biopsies might rapidly revolutionize oncology practice in allowing administration of more effective treatments. Liquid biopsies also provide an approach towards short-term monitoring of metastatic cancer patients to evaluate efficacy of treatment and/or early detection of secondary mutations responsible for resistance to treatment. In this context, pathologists, who have already been required in recent years to take interest in the domain of molecular pathology of cancer, now face new challenges. The attitude of pathologists to and level of involvement in the practice of liquid biopsies, including mastering the methods employed in molecular analysis of blood samples, need close attention. Regardless of the level of involvement of pathologists in this new field, it is mandatory that oncologists, biologists, geneticists, and pathologists work together to coordinate the pre-analytical, analytical, and post-analytical phases of molecular assessment of tissue and liquid samples of individual cancer patients. The challenges include (1) implementation of effective and efficient procedures for reception and analysis of liquid and tissue samples for histopathological and molecular evaluation and (2) assuring short turn-around times to facilitate rapid optimization of individual patient treatment. In this paper, we will review the following: (1) recent data concerning the concept of liquid biopsies in oncology and its development for patient care, (2) advantages and limitations of molecular analyses performed on blood samples compared to those performed on tissue samples, and (3) short-term challenges facing pathologists in dealing with liquid biopsies of cancer patients and new strategies to early detect metastatic tumor cell clones. PMID- 27553355 TI - Tbx3 overexpression in human gastric cancer is correlated with advanced tumor stage and nodal status and promotes cancer cell growth and invasion. AB - The objective of the current study was to investigate the expression pattern of Tbx3 and its clinicopathological significance in patients with gastric cancer. The expression pattern of Tbx3 in gastric cancer tissues and adjacent noncancerous surface epithelia and mucosal glands was detected by immunohistochemistry. Tbx3 was found to be overexpressed in 46 of 98 human gastric cancer samples, and this correlated with advanced clinical stage, tumor stage, and nodal status. In addition, in the SGC-7901 gastric cancer cell line, Tbx3 overexpression by plasmid transfection promoted growth and invasion. Conversely, depleting Tbx3 expression by small-interfering RNA inhibited proliferation and invasion in BGC-823 cell line. Moreover, Tbx3 accelerated cell cycle progression at the G1/S boundary. Tbx3 also regulated epithelial-to mesenchymal transition (EMT) to promote cell invasion by repressing E-cadherin expression and increasing expression levels N-cadherin, vimentin. These results indicate that in gastric cancer, Tbx3 plays an important role and might be a useful therapy target. PMID- 27553357 TI - Cigarette prices and community price comparisons in US military retail stores. AB - BACKGROUND: Tobacco pricing impacts use, yet military retailers sell discounted cigarettes. No systematic research has examined how military retail stores use internal community comparisons to set prices. We analysed data obtained through a Freedom of Information Act request on community price comparisons used by military retail to set cigarette prices. METHODS: Data on cigarette prices were obtained directly from military retailers (exchanges) from January 2013 to March 2014. Complete pricing data were obtained from exchanges on 114 military installations. RESULTS: The average price for a pack of Marlboro cigarettes in military exchanges was US$5.51, which was similar to the average lowest community price (US$5.45; mean difference=-0.06; p=0.104) and almost a US$1.00 lower than the average highest price (US$6.44). Military retail prices were 2.1%, 6.2% and 13.7% higher than the lowest, average and highest community comparisons, respectively, and 18.2% of exchange prices violated pricing instructions. There was a negative correlation (r=-0.21, p=0.02) between the number of community stores surveyed and exchange cigarette prices. CONCLUSIONS: There was no significant difference between prices for cigarettes on military installations and the lowest average community comparison, and in some locations, the prices violated Department of Defense (DoD) policy. US Marine Corps exchanges had the lowest prices, which is of concern given that the Marines also have the highest rates of tobacco use in the DoD. Given the relationship between tobacco product prices and demand, a common minimum (or floor) shelf price for tobacco products should be set for all exchanges and discount coupon redemptions should be prohibited. PMID- 27553356 TI - Ectopic KNOX Expression Affects Plant Development by Altering Tissue Cell Polarity and Identity. AB - Plant development involves two polarity types: tissue cell (asymmetries within cells are coordinated across tissues) and regional (identities vary spatially across tissues) polarity. Both appear altered in the barley (Hordeum vulgare) Hooded mutant, in which ectopic expression of the KNOTTED1-like Homeobox (KNOX) gene, BKn3, causes inverted polarity of differentiated hairs and ectopic flowers, in addition to wing-shaped outgrowths. These lemma-specific effects allow the spatiotemporal analysis of events following ectopic BKn3 expression, determining the relationship between KNOXs, polarity, and shape. We show that tissue cell polarity, based on localization of the auxin transporter SISTER OF PINFORMED1 (SoPIN1), dynamically reorients as ectopic BKn3 expression increases. Concurrently, ectopic expression of the auxin importer LIKE AUX1 and boundary gene NO APICAL MERISTEM is activated. The polarity of hairs reflects SoPIN1 patterns, suggesting that tissue cell polarity underpins oriented cell differentiation. Wing cell files reveal an anisotropic growth pattern, and computational modeling shows how polarity guiding growth can account for this pattern and wing emergence. The inverted ectopic flower orientation does not correlate with SoPIN1, suggesting that this form of regional polarity is not controlled by tissue cell polarity. Overall, the results suggest that KNOXs trigger different morphogenetic effects through interplay between tissue cell polarity, identity, and growth. PMID- 27553358 TI - Crosstalk in skin: melanocytes, keratinocytes, stem cells, and melanoma. AB - In the vertebrate embryo, melanocytes arise from the neural crest, migrate to and colonize the basal layer within the skin and skin appendages. Post-migratory melanocytes are securely attached to the basement membrane, and their morphology, growth, adhesion, and migration are under control of neighboring keratinocytes. Melanoma is a malignant tumor originated from melanocytes or their progenitor cells. During melanocyte transformation and melanoma progression, melanocytes lose their interactions with keratinocytes, resulting in uncontrolled proliferation and invasion of the malignant cells. Melanoma cells at the advanced stages often lack melanocytic features and resemble multipotent progenitors, which are a potential melanocyte reservoir in human skin. In this mini-review, we will summarize findings on cell-cell interactions that are responsible for normal melanocyte homeostasis, stem cell self-renewal, and differentiation. Our ultimate goal is to define molecules and pathways, which are essential for normal cell cell interactions but deregulated in melanoma formation and progression. PMID- 27553359 TI - Socioeconomic disparities in psychological distress in a nationally representative sample of Japanese adolescents: A time trend study. AB - OBJECTIVE: Socioeconomic status as a determinant of mental health problems has received scant attention in Japan, which has long been considered an egalitarian society. This study examined the association between socioeconomic status and psychological distress and its trends over 6 years among Japanese adolescents. METHODS: We used data from a nationally representative sample of 9491 adolescents aged 12-18 years who participated in three repeated cross-sectional surveys between 2007 and 2013. The K6 scale was used to assess psychological distress. Socioeconomic status indicators included household income, parental education, parental working status and household structure. RESULTS: Psychological distress prevalence decreased significantly from 2007 (10.7%) to 2013 (7.6%). However, the socioeconomic status patterns of psychological distress were consistent through the study period. Adolescents living in both lower (odds ratio = 1.61; 95% confidence interval = [1.27, 2.05]) and higher income households (odds ratio = 1.30; 95% confidence interval = [1.03, 1.62]) were more likely to report psychological distress than their middle-income counterparts. Adolescents with low household income were more likely to feel stress from interpersonal relationships and less likely to have help-seeking behaviors, while those with high household income were more likely to feel stress about school achievement. Psychological distress was also associated with parental poor education and single parenthood. CONCLUSIONS: Socioeconomic status disparities in adolescent psychological distress were evident and consistent during the 6-year period. There is a unique U-shaped relationship between household income and psychological distress among adolescents in Japan, unlike those from other countries. However, the underlying mechanisms may differ by income status. Future prevention efforts should consider socioeconomic status as a determinant of adolescent mental health problems. PMID- 27553360 TI - Efficacy of pregabalin augmentation for refractory pain in late-life depression. PMID- 27553361 TI - Entertainment-Education Narrative Versus Nonnarrative Interventions to Educate and Motivate Latinas to Engage in Mammography Screening. AB - BACKGROUND: The evidence is limited comparing the effects of entertainment education (E-E) narrative versus nonnarrative interventions to educate and motivate Latinas to engage in mammography screening. AIMS: This study compared an E-E narrative intervention to two nonnarrative interventions' effects among Latinas on breast cancer knowledge and motivation, as measured by changes in self efficacy, behavioral norms, and behavioral intentions to engage in mammography screening. METHOD: A sample of 141 Spanish-speaking Latinas was randomly assigned to one of three arms: an E-E narrative video, a nonnarrative educational video, and printed educational materials. Using a repeated measures design, the influence of the E-E narrative on pretest to posttest measures was assessed and compared to the influence of the other two interventions. RESULTS: The E-E narrative and nonnarrative interventions significantly increased Latinas' breast cancer knowledge, mammography self-efficacy, and behavioral norms from pretest to posttest. However, the E-E narrative participants' pretest to posttest difference in mammography self-efficacy was significantly higher when compared to the difference of the other two interventions. The effect of the E-E narrative intervention on self-efficacy and behavioral norms was moderated by the participants' absorption in the story and identification with the story characters. CONCLUSION: E-E narrative and nonnarrative interventions significantly educated and motivated Latinas to engage in mammography screening. The effects on mammography self-efficacy, an important precursor to behavior change, can be more strongly influenced by E-E narratives. DISCUSSION: Although E E narrative and nonnarrative interventions were effective, the need still exists to assess if they can ultimately influence lifesaving breast cancer screening behaviors. PMID- 27553362 TI - Intramyocardial Gene Therapy Directed to Hibernating Heart Muscle Using a Combination of Electromechanical Mapping and Positron Emission Tomography. AB - Cardiac gene transfer for the treatment of ischemic diseases has suffered from low gene transfer efficiency and inability to target treatment genes to the ischemic myocardium. A combined method has been developed based on electromechanical mapping and radiowater PET imaging to target gene therapy to viable but ischemic and hibernating areas of the myocardium. Electromechanical NOGA mapping produces three-dimensional images of myocardium with both an electric activity map and a myocardial contractility map. These have been converted to 17-segment 2D bull's-eye maps, which were superimposed onto PET radiowater perfusion imaging maps of the myocardium. This technique was applied in a Phase I/IIa clinical trial to target gene therapy for refractory angina patients. It was found that by combining electromechanical map with PET imaging, targeting of gene therapy to hibernating ischemic myocardium can be significantly improved. Here, the methods for the identification of viable, ischemic, and hibernating myocardium for gene transfer are described, and examples of treated refractory angina patients who have benefited from the improved gene transfer method to the ischemic myocardium are presented. PMID- 27553363 TI - The molecular pathogenesis of morphoea: from genetics to future treatment targets. AB - A number of immunoinflammatory and profibrotic mechanisms are recognized in the pathogenesis of broad sclerotic skin processes and, more specifically, morphoea. However, the precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood but of great clinical and therapeutic relevance. Regional susceptibility mechanisms (e.g. environmental triggers, mosaicism and positional identity) together with distinct pathogenic determinants (including innate, adaptive and imbalanced pro- and antifibrotic signalling pathways) are likely implicated. In the age of genetic profiling and personalized medicine, improved characterization of the environmental, systemic, local, genetic and immunopathological factors underpinning morphoea pathogenesis may open the door to novel targeted therapeutic approaches. PMID- 27553365 TI - Superacid Passivation of Crystalline Silicon Surfaces. AB - The reduction of parasitic recombination processes commonly occurring within the silicon crystal and at its surfaces is of primary importance in crystalline silicon devices, particularly in photovoltaics. Here we explore a simple, room temperature treatment, involving a nonaqueous solution of the superacid bis(trifluoromethane)sulfonimide, to temporarily deactivate recombination centers at the surface. We show that this treatment leads to a significant enhancement in optoelectronic properties of the silicon wafer, attaining a level of surface passivation in line with state-of-the-art dielectric passivation films. Finally, we demonstrate its advantage as a bulk lifetime and process cleanliness monitor, establishing its compatibility with large area photoluminescence imaging in the process. PMID- 27553364 TI - The assessment and management of pain in patients with dementia in hospital settings: a multi-case exploratory study from a decision making perspective. AB - BACKGROUND: Pain is often poorly managed in people who have a dementia. Little is known about how this patient population is managed in hospital, with research to date focused mainly on care homes. This study aimed to investigate how pain is recognised, assessed and managed in patients with dementia in a range of acute hospital wards, to inform the development of a decision support tool to improve pain management for this group. METHODS: A qualitative, multi-site exploratory case study. Data were collected in four hospitals in England and Scotland. Methods included non-participant observations, audits of patient records, semi structured interviews with staff and carers, and analysis of hospital ward documents. Thematic analysis was performed through the lens of decision making theory. RESULTS: Staff generally relied on patients' self-report of pain. For patients with dementia, however, communication difficulties experienced because of their condition, the organisational context, and time frames of staff interactions, hindered patients' ability to provide staff with information about their pain experience. This potentially undermined the trials of medications used to provide pain relief to each patient and assessments of their responses to these treatments. Furthermore, given the multidisciplinary environment, a patient's communication about their pain involved several members of staff, each having to make sense of the patient's pain as in an 'overall picture'. Information about patients' pain, elicited in different ways, at different times and by different health care staff, was fragmented in paper-based documentation. Re-assembling the pieces to form a 'patient specific picture of the pain' required collective staff memory, 'mental computation' and time. CONCLUSIONS: There is a need for an efficient method of eliciting and centralizing all pain related information for patients with dementia, which is distributed in time and between personnel. Such a method should give an overall picture of a patient's pain which is rapidly accessible to all involved in their care. This would provide a much-needed basis for making decisions to support the effective management of the pain of older people with dementia in hospital. PMID- 27553367 TI - Silencing of Apurinic/Apyrimidinic Endonuclease 1 Inhibits the Growth and Migration in Ovarian Cancer Cell via Activator-Protein-1 Signaling. AB - BACKGROUND: We hypothesized that apurinic/apyrimidinic endonuclease 1 (APE1) may regulate cell activity via activator protein 1 (AP-1) signaling pathway through its redox function in the development of ovarian cancer. METHODS: Ovarian cancer and paired paracarcinoma tissues were collected for determining APE1 expression with immunohistochemistry. Cell transfection was performed to silence APE1. For mRNA and protein expressions of genes after silencing, real-time reverse transcription polymerase chain reaction and Western blot assay were conducted. Transwell cell proliferation experiment and clone formation assay were conducted for cell proliferation; Transwell cell migration and cell invasion assays were conducted for cell migration and invasion. RESULTS: Most cancer tissues had APE1 cytoplasmic expression and a few had nuclear/cytoplasmic expression while few had only nuclear expression. A significantly higher APE1 expression was identified in cancer tissues than in paracarcinoma tissues and it was correlated with the clinicopathologic features. SKOV3 was used for cell experiments. After silencing of APE1, both mRNA and protein expressions of APE1 and AP-1 signaling-related genes were downregulated, and the cell activity in proliferation, migration and invasion was remarkably suppressed. CONCLUSION: Overexpressed APE1 promotes ovarian cancer growth and metastasis. Downregulated APE1 could suppress cell activity via AP-1 pathway, suggesting that APE1 gene may be a potential therapeutic target for ovarian cancer. PMID- 27553366 TI - Cancer network activity associated with therapeutic response and synergism. AB - BACKGROUND: Cancer patients often show no or only modest benefit from a given therapy. This major problem in oncology is generally attributed to the lack of specific predictive biomarkers, yet a global measure of cancer cell activity may support a comprehensive mechanistic understanding of therapy efficacy. We reasoned that network analysis of omic data could help to achieve this goal. METHODS: A measure of "cancer network activity" (CNA) was implemented based on a previously defined network feature of communicability. The network nodes and edges corresponded to human proteins and experimentally identified interactions, respectively. The edges were weighted proportionally to the expression of the genes encoding for the corresponding proteins and relative to the number of direct interactors. The gene expression data corresponded to the basal conditions of 595 human cancer cell lines. Therapeutic responses corresponded to the impairment of cell viability measured by the half maximal inhibitory concentration (IC50) of 130 drugs approved or under clinical development. Gene ontology, signaling pathway, and transcription factor-binding annotations were taken from public repositories. Predicted synergies were assessed by determining the viability of four breast cancer cell lines and by applying two different analytical methods. RESULTS: The effects of drug classes were associated with CNAs formed by different cell lines. CNAs also differentiate target families and effector pathways. Proteins that occupy a central position in the network largely contribute to CNA. Known key cancer-associated biological processes, signaling pathways, and master regulators also contribute to CNA. Moreover, the major cancer drivers frequently mediate CNA and therapeutic differences. Cell-based assays centered on these differences and using uncorrelated drug effects reveals novel synergistic combinations for the treatment of breast cancer dependent on PI3K-mTOR signaling. CONCLUSIONS: Cancer therapeutic responses can be predicted on the basis of a systems-level analysis of molecular interactions and gene expression. Fundamental cancer processes, pathways, and drivers contribute to this feature, which can also be exploited to predict precise synergistic drug combinations. PMID- 27553368 TI - Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity. AB - Molecular diagnosis of hereditary breast and ovarian cancer (HBOC) by standard methodologies has been limited to the BRCA1 and BRCA2 genes. With the recent development of new sequencing methodologies, the speed and efficiency of DNA testing have dramatically improved. The aim of this work was to validate the use of next-generation sequencing (NGS) for the detection of BRCA1/BRCA2 point mutations in a diagnostic setting and to study the role of other genes associated with HBOC in Portuguese families. A cohort of 94 high-risk families was included in the study, and they were initially screened for the two common founder mutations with variant-specific methods. Fourteen index patients were shown to carry the Portuguese founder mutation BRCA2 c.156_157insAlu, and the remaining 80 were analyzed in parallel by Sanger sequencing for the BRCA1/BRCA2 genes and by NGS for a panel of 17 genes that have been described as involved in predisposition to breast and/or ovarian cancer. A total of 506 variants in the BRCA1/BRCA2 genes were detected by both methodologies, with a 100 % concordance between them. This strategy allowed the detection of a total of 39 deleterious mutations in the 94 index patients, namely 10 in BRCA1 (25.6 %), 21 in BRCA2 (53.8 %), four in PALB2 (10.3 %), two in ATM (5.1 %), one in CHEK2 (2.6 %), and one in TP53 (2.6 %), with 20.5 % of the deleterious mutations being found in genes other than BRCA1/BRCA2. These results demonstrate the efficiency of NGS for the detection of BRCA1/BRCA2 point mutations and highlight the genetic heterogeneity of HBOC. PMID- 27553369 TI - Linking major depression and the neural substrates of associative processing. AB - It has been proposed that mood correlates with the breadth of associative thinking. Here we set this hypothesis to the test in healthy and depressed individuals. Generating contextual associations engages a network of cortical regions including the parahippocampal cortex (PHC), retrosplenial complex, and medial prefrontal cortex. The link between mood, associative processing, and its underlying cortical infrastructure provides a promising avenue for elucidating the mechanisms underlying the cognitive impairments in major depressive disorder (MDD). The participants included 15 nonmedicated individuals with acute major depressive episodes and 15 healthy matched controls. In an fMRI experiment, participants viewed images of objects that were either strongly or weakly associated with a specific context (e.g., a beach chair vs. a water bottle) while rating the commonality of each object. Analyses were performed to examine the brain activation and structural differences between the groups. Consistent with our hypothesis, controls showed greater activation of the contextual associations network than did depressed participants. In addition, PHC structural volume was correlated with ruminative tendencies, and the volumes of the hippocampal subfields were significantly smaller in depressed participants. Surprisingly, depressed participants showed increased activity in the entorhinal cortex (ERC), as compared with controls. We integrated these findings within a mechanistic account linking mood and associative thinking and suggest directions for the future. PMID- 27553370 TI - The tumor as an organ: comprehensive spatial and temporal modeling of the tumor and its microenvironment. AB - BACKGROUND: Research related to cancer is vast, and continues in earnest in many directions. Due to the complexity of cancer, a better understanding of tumor growth dynamics can be gleaned from a dynamic computational model. We present a comprehensive, fully executable, spatial and temporal 3D computational model of the development of a cancerous tumor together with its environment. RESULTS: The model was created using Statecharts, which were then connected to an interactive animation front-end that we developed especially for this work, making it possible to visualize on the fly the on-going events of the system's execution, as well as the effect of various input parameters. We were thus able to gain a better understanding of, e.g., how different amounts or thresholds of oxygen and VEGF (vascular endothelial growth factor) affect the progression of the tumor. We found that the tumor has a critical turning point, where it either dies or recovers. If minimum conditions are met at that time, it eventually develops into a full, active, growing tumor, regardless of the actual amount; otherwise it dies. CONCLUSIONS: This brings us to the conclusion that the tumor is in fact a very robust system: changing initial values of VEGF and oxygen can increase the time it takes to become fully developed, but will not necessarily completely eliminate it. PMID- 27553371 TI - Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, 2014. AB - BACKGROUND: During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS: A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. RESULTS: The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% [22/39] vs 35.3% [30/85]; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% [11/17]) was higher than that of the control group (27.8% [5/18]). Furthermore, the average survival time of the treatment group (46.9 +/- 5.6 days) was longer than that of the control group (28.9 +/- 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. CONCLUSIONS: Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD. PMID- 27553372 TI - Reply to Meshnick and Hastings et al. PMID- 27553373 TI - Artemisinin Resistance in Southeast Asia. PMID- 27553374 TI - Editorial Commentary: Considerations of Favipiravir as a Medical Countermeasure in Future Randomized Controlled Trials Against Ebola Virus Disease. PMID- 27553376 TI - Real-Life Use of Isavuconazole in Patients Intolerant to Other Azoles. PMID- 27553375 TI - Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials. AB - BACKGROUND: Interferon-based hepatitis C virus (HCV) therapy is safe and effective among people receiving opioid substitution therapy (OST), but treatment uptake remains low. Our aim was to evaluate the impact of OST and drug use during therapy on completion, adherence, sustained virologic response (SVR12), and safety of ledipasvir/sofosbuvir +/- ribavirin. METHODS: The phase 3 ION studies evaluated a fixed-dose combination of ledipasvir/sofosbuvir +/- ribavirin administered for 8, 12, or 24 weeks in patients with chronic HCV genotype 1. People with clinically significant drug use (prior 12 months) or noncannabinoids detected at screening by urine drug tests (not explained by prescriptions) were ineligible. Stored samples were available from ION-1 for retrospective testing for illicit drugs by enzyme-linked immunosorbent assay. RESULTS: Among 1952 patients enrolled in the ION studies, 4% (n = 70) were receiving OST. Among those receiving (n = 70) and not receiving OST (n = 1882), there was no difference in treatment completion (97% vs 98%; P = .40), >=80% adherence (93% vs 92%; P = 1.00), SVR12 (94% vs 97%; P = .28), and serious adverse events (4% vs 3%; P = .43), respectively. Among participants in the ION-1 trial, 23% (n = 196) used illicit drugs during therapy (15% cannabinoids alone; 8% other illicit drugs +/- cannabinoids). There was no difference in treatment completion, >=80% adherence, SVR12, or serious AEs in those with no drug use during treatment compared with those who used cannabinoids and/or other illicit drugs. No cases of HCV reinfection were observed in the 24 weeks following treatment. CONCLUSIONS: OST and drug use during HCV therapy did not impact treatment completion, adherence, SVR12, or safety. CLINICAL TRIALS REGISTRATION: ION-1 (NCT01701401); ION-2 (NCT01768286); and ION-3 (NCT01851330). PMID- 27553377 TI - Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials. AB - In this analysis of the ASTRAL trials (non-opioid substitution therapy [OST], n = 984; OST, n = 51) evaluating the once-daily, pan-genotypic regimen of sofosbuvir/velpatasvir for hepatitis C virus infection, OST did not impact completion, adherence, sustained virologic response (SVR12), or safety. SVR12 was 96% (95% confidence interval, 87%, >99%) in those receiving OST. PMID- 27553378 TI - Lung hyperaeration assessment by computed tomography: correction of reconstruction-induced bias. AB - BACKGROUND: Computed tomography (CT) reconstruction parameters, such as slice thickness and convolution kernel, significantly affect the quantification of hyperaerated parenchyma (VHYPER%). The aim of this study was to investigate the mathematical relation between VHYPER% calculated at different reconstruction settings, in mechanically ventilated and spontaneously breathing patients with different lung pathology. METHODS: In this retrospective observational study, CT scans of patients of the intensive care unit and emergency department were collected from two CT scanners and analysed with different kernel-thickness combinations (reconstructions): 1.25 mm soft kernel, 5 mm soft kernel, 5 mm sharp kernel in the first scanner; 2.5 mm slice thickness with a smooth (B41s) and a sharp (B70s) kernel on the second scanner. A quantitative analysis was performed with Maluna(r) to assess lung aeration compartments as percent of total lung volume. CT variables calculated with different reconstructions were compared in pairs, and their mathematical relationship was analysed by using quadratic and power functions. RESULTS: 43 subjects were included in the present analysis. Image reconstruction parameters influenced all the quantitative CT-derived variables. The most relevant changes occurred in the hyperaerated and normally aerated volume compartments. The application of a power correction formula led to a significant reduction in the bias between VHYPER% estimations (p < 0.001 in all cases). The bias in VHYPER% assessment did not differ between lung pathology nor ventilation mode groups (p > 0.15 in all cases). CONCLUSIONS: Hyperaerated percent volume at different reconstruction settings can be described by a fixed mathematical relationship, independent of lung pathology, ventilation mode, and type of CT scanner. PMID- 27553379 TI - The impact of H63D HFE gene carriage on hemoglobin and iron status in children. AB - The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. Hereditary hemochromatosis is a heterogenic metabolic syndrome which is due to unchecked transfer of iron into the bloodstream and its toxic effects on parenchymatous organs. It is caused by the mutation of genes that encode proteins that help hepcidin to monitor serum iron. These proteins include the human hemochromatosis protein -HFE, transferrin-receptor 2, hemojuvelin in rare instances, and ferroportin. HFE-related hemochromatosis is the most frequent form of the disease. Interestingly, the low penetrance of polymorphic HFE genes results in rare clinical presentation of the disease, predominantly in middle-aged males. Taking into account the wide dispersion of HFE mutation in our population and also its unknown role in heterozygotes, we analyzed the impact of H63D HFE carriage in the developmental age, with respect to gender, on the iron status and hemoglobin concentration of carriers in comparison to those of wild-type HFE gene (12.7 +/- 3.07 years, 42 boys and 41 girls). H63D carriers presented higher blood iron, transferrin saturation, and ferritin concentration than wild-type probands (p < 0.05.) Interestingly, male H63D carriers showed higher hemoglobin concentration than the unburdened children. Moreover, in the H63D carrier group, a positive correlation between iron and hemoglobin was noted. In conclusion, this study demonstrates that changes in iron metabolism occur at a young age in HFE heterozygotes. PMID- 27553380 TI - The predictive value of selected serum microRNAs for acute GVHD by TaqMan MicroRNA arrays. AB - Currently, the diagnosis of acute graft-versus-host disease (aGVHD) is mainly based on clinical symptoms and biopsy results. This study was designed to further explore new no noninvasive biomarkers for aGVHD prediction/diagnosis. We profiled miRNAs in serum pools from patients with aGVHD (grades II-IV) (n = 9) and non aGVHD controls (n = 9) by real-time qPCR-based TaqMan MicroRNA arrays. Then, predictive models were established using related miRNAs (n = 38) and verified by a double-blind trial (n = 54). We found that miR-411 was significantly down regulated when aGVHD developed and recovered when aGVHD was controlled, which demonstrated that miR-411 has potential as an indicator for aGVHD monitoring. We developed and validated a predictive model and a diagnostic model for aGVHD. The predictive model included two miRNAs (miR-26b and miR-374a), which could predict an increased risk for aGVHD 1 or 2 weeks in advance, with an AUC, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of 0.722, 76.19 %, and 69.70 %, respectively. The diagnostic model included three miRNAs (miR-28-5p, miR-489, and miR-671-3p) with an AUC, PPV, and NPV of 0.841, 85.71 % and 83.33 %, respectively. Our results show that circulating miRNAs (miR-26b and miR-374a, miR 28-5p, miR-489 and miR-671-3p) may serve as biomarkers for the prediction and diagnosis of grades II-IV aGVHD. PMID- 27553381 TI - Additive-Free Transparent Triarylamine-Based Polymeric Hole-Transport Materials for Stable Perovskite Solar Cells. AB - Triarylamine-based polymers with different functional groups were synthetized as hole-transport materials (HTMs) for perovskite solar cells (PSCs). The novel materials enabled efficient PSCs without the use of chemical doping (or additives) to enhance charge transport. Devices employing poly(triarylamine) with methylphenylethenyl functional groups (V873) showed a power conversion efficiency of 12.3 %, whereas widely used additive-free poly[bis(4-phenyl)(2,4,6 trimethylphenyl)amine] (PTAA) demonstrated 10.8 %. Notably, devices with V873 enabled stable PSCs under 1 sun illumination at maximum power point tracking for approximately 40 h at room temperature, and in the dark under elevated temperature (85 degrees C) for more than 140 h. This is in stark contrast to additive-containing devices, which degrade significantly within the same time frame. The results present remarkable progress towards stable PSC under real working conditions and industrial stress tests. PMID- 27553382 TI - Influence of Surface Passivation on AlN Barrier Stress and Scattering Mechanism in Ultra-thin AlN/GaN Heterostructure Field-Effect Transistors. AB - Ultra-thin AlN/GaN heterostructure field-effect transistors (HFETs) with, and without, SiN passivation were fabricated by the same growth and device processes. Based on the measured DC characteristics, including the capacitance-voltage (C-V) and output current-voltage (I-V) curves, the variation of electron mobility with gate bias was found to be quite different for devices with, and without, SiN passivation. Although the AlN barrier layer is ultra thin (c. 3 nm), it was proved that SiN passivation induces no additional tensile stress and has no significant influence on the piezoelectric polarization of the AlN layer using Hall and Raman measurements. The SiN passivation was found to affect the surface properties, thereby increasing the electron density of the two-dimensional electron gas (2DEG) under the access region. The higher electron density in the access region after SiN passivation enhanced the electrostatic screening for the non-uniform distributed polarization charges, meaning that the polarization Coulomb field scattering has a weaker effect on the electron drift mobility in AlN/GaN-based devices. PMID- 27553383 TI - Optical Addressing Electronic Tongue Based on Low Selective Photovoltaic Transducer with Nanoporous Silicon Layer. AB - The electronic tongue based on the array of low selective photovoltaic (PV) sensors and principal component analysis is proposed for detection of various alcohol solutions. A sensor array is created at the forming of p-n junction on silicon wafer with porous silicon layer on the opposite side. A dynamical set of sensors is formed due to the inhomogeneous distribution of the surface recombination rate at this porous silicon side. The sensitive to molecular adsorption photocurrent is induced at the scanning of this side by laser beam. Water, ethanol, iso-propanol, and their mixtures were selected for testing. It is shown that the use of the random dispersion of surface recombination rates on different spots of the rear side of p-n junction and principal component analysis of PV signals allows identifying mentioned liquid substances and their mixtures. PMID- 27553384 TI - Weakening of Indian Summer Monsoon Rainfall due to Changes in Land Use Land Cover. AB - Weakening of Indian summer monsoon rainfall (ISMR) is traditionally linked with large-scale perturbations and circulations. However, the impacts of local changes in land use and land cover (LULC) on ISMR have yet to be explored. Here, we analyzed this topic using the regional Weather Research and Forecasting model with European Center for Medium range Weather Forecast (ECMWF) reanalysis data for the years 2000-2010 as a boundary condition and with LULC data from 1987 and 2005. The differences in LULC between 1987 and 2005 showed deforestation with conversion of forest land to crop land, though the magnitude of such conversion is uncertain because of the coarse resolution of satellite images and use of differential sources and methods for data extraction. We performed a sensitivity analysis to understand the impacts of large-scale deforestation in India on monsoon precipitation and found such impacts are similar to the observed changes in terms of spatial patterns and magnitude. We found that deforestation results in weakening of the ISMR because of the decrease in evapotranspiration and subsequent decrease in the recycled component of precipitation. PMID- 27553385 TI - Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial. AB - BACKGROUND: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. METHODS/DESIGN: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. DISCUSSION: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02560922 , registered 9/22/2015. PMID- 27553388 TI - Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau. AB - This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302-480 km, while the annual precipitation showed smaller scales of 111 182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions. PMID- 27553387 TI - Chikungunya in the region of the Americas. A challenge for rheumatologists and health care systems. AB - At the end of 2013, the Pan American Health Organization issued an epidemiological alert due to the detection of the first local cases of Chikungunya in the Americas. By August 2015, autochthonous transmissions were detected in 33 countries and territories of the Americas. Latin America has reported nearly one million cases; only Colombia has issued a report of >200,000 cases during the first 4 months of 2015. In some Latin American and Caribbean countries, Chikungunya becomes a major public health problem. The disease commonly exhibits a self-limited course of arthritis, usually lasting for a few days or that may be prolonged to weeks; however, in 10-60 % of cases, joint pain may become chronic and persist for up to 3-5 years. Human-caused environmental changes, such as climate change, the globalization of international exchange, and disordered urban growth, are some factors that aid in its emergence and dissemination. Outbreaks of Chikungunya comprise a challenge for health care systems and rheumatologists because of the high attack rate on the population and the anticipated development of post-Chikungunya chronic rheumatism. This review emphasizes the rheumatologic clinical manifestations reported in the American continent and highlights the challenges that health care systems face in the absence of an effective vaccine and specific treatment to fight Chikungunya. PMID- 27553386 TI - Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study. AB - Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA. PMID- 27553389 TI - Monosegmental vs bisegmental pedicle fixation for the treatment of thoracolumbar spine fractures. AB - INTRODUCTION: The anatomy and biomechanics of the thoracolumbar spine place these segments at high risk of trauma injuries. Treatment options are either conservative or surgical, and there is a lack of consensus about the right indications. International scientific publications agree only on basic surgical principles: vertebral stability, deformity correction, protection of neurological structures and fast functional recovery. The most commonly used approach is the posterior approach, which allows the best management of most vertebral fracture patterns. The aim of this study was to compare clinical and radiological outcomes of monosegmental stabilisation with those of bisegmental stabilisation and fusion in the treatment of traumatic thoracolumbar spine fractures. MATERIALS AND METHODS: This retrospective clinical and radiological study evaluated 48 consecutive patients treated with monosegmental (Group M; n=14) or bisegmental (Group B; n=34) posterior pedicular instrumentation for thoracolumbar fractures. Fractures were classified by the new AO Spine TLIC system. Average follow-up was 30 months. Clinical outcomes in both groups were statistically compared. Radiological outcomes were evaluated in terms of vertebral anterior body height restoration and correction of the kyphotic deformity. RESULTS: Radiographical results showed no statistically significant difference between the two groups in vertebral body height restoration and correction of the kyphotic deformity. The mean postoperative somatic vertebral anterior body height in Group M was 25.8+/ 4.52mm and in Group B it was 24.43+/-4.27mm. In Group M the mean postoperative kyphotic deformity was 11.10+/-5.71 degrees , in Group B it was 9.09+/-4.93 degrees . CONCLUSIONS: The results of this study confirm the validity of short and very short instrumentation for the treatment of well-selected type A and B vertebral fractures. In C type fractures correct surgical indication must be evaluated on an individual basis. PMID- 27553390 TI - Cost Analysis of 48 Burn Patients in a Mass Casualty Explosion Treated at Chang Gung Memorial Hospital. AB - INTRODUCTION: Little is known about the costs of treating burn patients after a mass casualty event. A devastating Color Dust explosion that injured 499 patients occurred on June 27, 2015 in Taiwan. This study was performed to investigate the economic effects of treating burn patients at a single medical center after an explosion disaster. METHODS: A detailed retrospective analysis on 48 patient expense records at Chang Gung Memorial Hospital after the Color Dust explosion was performed. Data were collected during the acute treatment period between June 27, 2015 and September 30, 2015. The distribution of cost drivers for the entire patient cohort (n=48), patients with a percent total body surface area burn (%TBSA)>=50 (n=20), and those with %TBSA <50 (n=28) were analyzed. RESULTS: The total cost of 48 burn patients over the acute 3-month time period was $2,440,688, with a mean cost per patient of $50,848 +/-36,438. Inpatient ward fees (30%), therapeutic treatment fees (22%), and medication fees (11%) were found to be the three highest cost drivers. The 20 patients with a %TBSA >=50 consumed $1,559,300 (63.8%) of the total expenses, at an average cost of $77,965+/-34,226 per patient. The 28 patients with a %TBSA <50 consumed $881,387 (36.1%) of care expenses, at an average cost of $31,478+/-23,518 per patient. CONCLUSIONS: In response to this mass casualty event, inpatient ward fees represented the largest expense. Hospitals can reduce this fee by ensuring wound dressing and skin substitute materials are regionally stocked and accessible. Medication fees may be higher than expected when treating a mass burn cohort. In preparation for a future event, hospitals should anticipate patients with a %TBSA>=50 will contribute the majority of inpatient expenses. PMID- 27553391 TI - A Five-Year Review of Tag Rugby Hand Injuries. AB - Tag rugby is one of the fastest growing sports in Ireland. It is a soft-contact team game that is loosely based on the rugby league format except players try to remove Velcro tags from their opponents' shorts rather than engage in a typical rugby tackle. The purpose of this study was to examine all tag rugby associated hand injuries over a five-year period in three large tertiary referral hospitals in Ireland. Using the patient corresponding system, 228 patients with hand injury related tag rugby injuries were observed from 2010 to 2015. There were 138 males and 90 females in the study and over 40% of patients required surgery. Most of the patients were young professionals with an average age of 30. Twenty-five patients worked in the financial services whilst there were 23 teachers. Fractures accounted for 124 of the 228 injuries and mallet injuries accounted for 53. Eighty percent of all injuries occurred during the tackle. The mean number of days missed from work was 9.1+/-13.8 days. These injuries resulted in an average of seven hospital appointments per patient. Considering it is a soft-contact sport, it is surprising the number of hand injuries that we have observed. Although safety measures have been introduced to decrease the number of hand injuries in recent years, there is a need for further improvements. Better player education about seeking prompt medical attention once an injury occurs, coupled with longer shorts worn by players may improve measures for the sport. PMID- 27553392 TI - Oral Free Paper Sessions. PMID- 27553393 TI - No complexity-stability relationship in empirical ecosystems. AB - Understanding the mechanisms responsible for stability and persistence of ecosystems is one of the greatest challenges in ecology. Robert May showed that, contrary to intuition, complex randomly built ecosystems are less likely to be stable than simpler ones. Few attempts have been tried to test May's prediction empirically, and we still ignore what is the actual complexity-stability relationship in natural ecosystems. Here we perform a stability analysis of 116 quantitative food webs sampled worldwide. We find that classic descriptors of complexity (species richness, connectance and interaction strength) are not associated with stability in empirical food webs. Further analysis reveals that a correlation between the effects of predators on prey and those of prey on predators, combined with a high frequency of weak interactions, stabilize food web dynamics relative to the random expectation. We conclude that empirical food webs have several non-random properties contributing to the absence of a complexity-stability relationship. PMID- 27553394 TI - World Health Assembly: creating a supportive environment for health. PMID- 27553395 TI - Nutrient intake of infants and toddlers in the United Arab Emirates: the Feeding Infants and Toddlers Study. AB - This descriptive study evaluated the nutrient adequacy of the diet of infants (aged 6-11.9 months) and toddlers (aged 12-24 months) in the United Arab Emirates. A random sample of 1000 infants and toddlers was recruited from 2 cities (Al Ain and Dubai) from March 2011 to February 2012 and their usual nutrient intake was determined using 24-hour recall. In all, 54.2% of infants and 25.2% of toddlers were breastfeeding. Mean energy intake of infant girls in Al Ain and Dubai was 747 (SD 189) kcal and 773 (SD 215) kcal respectively and 810.5 (SD 232.2) kcal and 821.9 (SD 262) kcal for boys. In toddlers, mean energy intake for girls in Al Ain and Dubai was 1032.8 (SD 252) kcal and 1013 (SD 339.1) kcal respectively and 1057.2 (SD 201.8) kcal and 1030.3 (SD 341.7) kcal for boys. Iron intake was low in both groups. Mean body mass index and body weight and height were similar to World Health Organization figures but significant numbers of infants and toddlers of both sexes were over- or underweight. Although mean energy and macronutrient intakes were comparable to the RDA, significant numbers were over- or underfed. PMID- 27553396 TI - Prevalence of iodine deficiency disorders among school children in Saudi Arabia: results of a national iodine nutrition study. AB - This study aimed at establishing updated data on iodine nutrition among schoolchildren in Saudi Arabia. A cross-sectional cluster survey among schoolchildren aged 8-10 years was conducted during February-April 2012. Children were clinically examined for goitre, urine and household salt samples were collected to estimate urinary iodine concenteration (UIC) and iodine content in salt. The overall goitre prevalence at the national level among 4 016 children was 4.2%. The prevalence was < 5% in all regions of the country except southern region with a prevalence of 12.7%. The median UIC of 2224 samples was 133 MUg/L, with 74.3% of the surveyed children with UIC >= 100 MUg/L. Analysis of salt samples (n = 4242) revealed that 69.8% of households were consuming adequately iodized salt. The findings suggest iodine sufficiency at the national level, however southern region still has a goitre prevalence of mild degree severity and the proportion of households consuming adequately iodized salt is still below recommendations. PMID- 27553397 TI - Customer's self-audit to improve the technical quality of maternity care in Tabriz: a community trial. AB - Pregnant women have a major role to play in assessing and improving their own quality of care. This study in Tabriz, Islamic Republic of Iran, aimed to assess the effectiveness of an intervention for pregnant women-based on education and support groups and involvement in quality assessment activities-in order to improve the technical quality of public maternity care at public health centres. The intervention phase began in September 2011 and lasted 8 months. The outcome measure was health-care providers' degree of adherence to the Iranian maternity care standards. An intervention group of 92 pregnant women from 10 health centres was compared with a control group of 93 pregnant women from 11 centres. Logistic regression analysis showed that the self-assessed technical quality of maternity care received by the women was significantly better in the intervention that the control group for several of the standards concerning clinical examinations, maternal education and vitamin and mineral supplements. PMID- 27553398 TI - Psychometric properties of the Social Cognitive Theory questionnaire for physical activity in a sample of Iranian adolescent girl students. AB - This research examined the validity and reliability of a researcher-developed questionnaire based on Social Cognitive Theory (SCT) to assess the physical activity behaviour of Iranian adolescent girls (SCT-PAIAGS). Psychometric properties of the SCT-PAIAGS were assessed by determining its face validity, content and construct validity as well as its reliability. In order to evaluate factor structure, cross-sectional research was conducted on 400 high-school girls in Tehran. Content validity index, content validity ratio and impact score for the SCT-PAIAGS varied between 0.97-1, 0.91-1 and 4.6-4.9 respectively. Confirmatory factor analysis approved a six-factor structure comprising self efficacy, self-regulation, family support, friend support, outcome expectancy and self-efficacy to overcoming impediments. Factor loadings, t-values and fit indices showed that the SCT model was fitted to the data. Cronbach's alpha coefficient ranged from 0.78 to 0.85 and intraclass correlation coefficient from 0.73 to 0.90. PMID- 27553399 TI - Development of a method for classification of hospitals based on results of the diagnosis-related groups and the principle of case-mix index. AB - This research used DRGs and CMI to adjust medical waste production through the calculation of DRGs and CMI scores. These scores were used to assess the performances of teaching hospitals in Damascus. The linear correlations between these scores and the annual amount of waste and DRGs values were studied. The differences between the daily waste generations before and after the adjustment process were determined. Accordingly, the highest values of DRGs and CMI Scores were for the pediatric and Al Assad hospitals respectively. Among the teaching hospitals in Damascus, Al Assad has achieved the highest performance. Based on the results, the accuracy and homogeneity of medical waste generation rates were improved, which in turn leads to continuous improvement in the management of medical wastes. PMID- 27553400 TI - A qualitative study on a 30-year trend of tobacco use and tobacco control programmes in Islamic Republic of Iran. AB - We conducted in-depth interviews with key tobacco control policy-makers to explore their views and opinions of trends in tobacco use and the effectiveness of tobacco control programmes over the past 3 decades. A qualitative interview study was conducted in 2014 using a grounded theory approach. In-depth interviews were conducted with 86 key tobacco control policy-makers and data collection was based on principles of saturation. The core code "tobacco consumption and its control programme" was extracted and its related themes were listed. After review and classification by an expert panel, 9 categorized codes emerged. The final 31 codes were ordered according to their conceptual differentiations. Overall, tobacco consumption was constant over the past 3 decades; however it was increasing in females and young people and decreasing in older people; hookah consumption was increasing. A positive outcome is that tobacco use is now viewed negatively in the Islamic Republic of Iran, largely due to tobacco control programmes but the current situation is still not ideal and a comprehensive tobacco control law is needed. PMID- 27553401 TI - Characterization of invasive Neisseria meningitidis strains isolated at the Children's Hospital of Tunis, Tunisia. AB - Neisseria meningitidis, a leading cause of bacterial meningitis and other serious infections, is responsible for approximately one-third of cases of bacterial meningitis in the Children's Hospital of Tunis. The serogroup distribution, antibiotic susceptibility and antigenic and molecular characteristics of N. meningitidis isolates were determined in patients aged 3 days-13 years between February 1998 and June 2013. In all 107 invasive strains of N. meningitidis were isolated. Reduced susceptibility to penicillin G was seen in 55.7% of isolates, with a low level of resistance in all cases; 28.4% showed a low level of resistance to amoxicillin. Serogroup B isolates were the most frequent (80.4%), followed by serogroups C (12.2%) and A (5.6%). Isolates of serogroup A had the same antigenic formula (A:4:P1.9), the same variable regions VR1, VR2 and VR3, and belonged to the same clonal complex (CC5). Isolates of serogroups B and C were more heterogeneous with several antigenic formulae. The most frequent clonal complex in these isolates was CC35. Serogroup B accounted for a large percentage of our isolates with marked diversity. PMID- 27553402 TI - Zika virus: no cases in the Eastern Mediterranean Region but concerns remain. AB - Following the WHO declaration on 1 February 2016 of a Public Health Emergency of International Concern (PHEIC) with regard to clusters of microcephaly and neurological disorders potentially associated with Zika virus, the WHO Regional Office for the Eastern Mediterranean conducted three rounds of emergency meetings to address enhancing preparedness actions in the Region. The meetings provided up to-date information on the current situation and agreed on a set of actions for the countries to undertake to enhance their preparedness and response capacities to Zika virus infection and its complications. The most urgent action is to enhance both epidemiological and entomological surveillance between now and the coming rainy seasons in countries with known presence of Aedes mosquitoes. Zika virus like other vector-borne diseases poses a particular challenge to the countries because of their complex nature which requires multidisciplinary competencies and strong rapid interaction among committed sectors. WHO is working closely with partners and countries to ensure the optimum support is provided to the countries to reduce the risk of this newly emerged health threat. PMID- 27553403 TI - Mechanical properties, in vitro corrosion and biocompatibility of newly developed biodegradable Mg-Zr-Sr-Ho alloys for biomedical applications. AB - Our previous studies have demonstrated that Mg-Zr-Sr alloys can be anticipated as excellent biodegradable implant materials for load-bearing applications. In general, rare earth elements (REEs) are widely used in magnesium (Mg) alloys with the aim of enhancing the mechanical properties of Mg-based alloys. In this study, the REE holmium (Ho) was added to an Mg-1Zr-2Sr alloy at different concentrations of Mg1Zr2SrxHo alloys (x = 0, 1, 3, 5 wt. %) and the microstructure, mechanical properties, degradation behaviour and biocompatibility of the alloys were systematically investigated. The results indicate that the addition of Ho to Mg1Zr2Sr led to the formation of the intermetallic phases MgHo3, Mg2Ho and Mg17Sr2 which resulted in enhanced mechanical strength and decreased degradation rates of the Mg-Zr-Sr-Ho alloys. Furthermore, Ho addition (<=5 wt. %) to Mg-Zr-Sr alloys led to enhancement of cell adhesion and proliferation of osteoblast cells on the Mg-Zr-Sr-Ho alloys. The in vitro biodegradation and the biocompatibility of the Mg-Zr-Sr-Ho alloys were both influenced by the Ho concentration in the Mg alloys; Mg1Zr2Sr3Ho exhibited lower degradation rates than Mg1Zr2Sr and displayed the best biocompatibility compared with the other alloys. PMID- 27553404 TI - Evaluation of multiplex PCR using MPB64 and IS6110 primers for rapid diagnosis of tuberculous meningitis. AB - Tuberculous meningitis (TBM) is one of those most serious manifestations of extra pulmonary tuberculosis and prompt diagnosis and treatment is required for better clinical outcome. It is difficult to diagnose due to lack of rapid, sensitive, and specific tests. Newer methods, which are easy and reliable, are required to diagnose TBM at an early stage. Thus our aim was to evaluate the Multiplex polymerase chain reaction (PCR) technique, using primers directed against the insertion sequence IS6110 and MPB64 gene for the detection of Mycobacterium tuberculosis in Cerebrospinal fluid (CSF), for rapid diagnosis of TBM patients. 102 CSF samples were analyzed from patients suspected with TBM along with a control group of 10 patients having other neurological disorders. CSF sediments were analyzed individually for M. tuberculosis DNA by Multiplex PCR using two set of primers targeting insertion sequence IS6110 and gene MBp64, which is very specific for MTBC. Out of 37 patients diagnosed with TBM clinically, MPB64 PCR was positive in 22, IS6110 PCR was positive in 28, both PCR using Multiplex were positive in 34 and Microscopy was positive in one. Thus Sensitivity of MPB64 PCR, IS6110 PCR, Multiplex PCR and Microscopy were found to be 62.3%, 75.4%, 91.8% and 2.7% respectively. In non TBM group PCR was negative in all cases hence, the specificity was 100%. Multiplex PCR system using primers targeting IS6110 and MPB64, for the detection of M. tuberculosis DNA in CSF samples, has high sensitivity than any one of them alone, and could be used for the early detection of TBM in CSF samples. PMID- 27553405 TI - Efficacy of gene-therapy based on adenovirus encoding granulocyte-macrophage colony-stimulating factor in drug-sensitive and drug-resistant experimental pulmonary tuberculosis. AB - Tuberculosis (TB), although a curable disease, remains a major cause of morbidity and mortality worldwide. It is necessary to develop a short-term therapy with reduced drug toxicity in order to improve adherence rate and control disease burden. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be a key cytokine in the treatment of pulmonary TB since it primes the activation and differentiation of myeloid and non-myeloid precursor cells, inducing the release of protective Th1 cytokines. In this work, we administrated by intratracheal route recombinant adenoviruses encoding GM-CSF (AdGM-CSF). This treatment produced significant bacterial elimination when administered in a single dose at 60 days of infection with drug sensitive or drug resistant Mtb strains in a murine model of progressive disease. Moreover, AdGM-CSF combined with primary antibiotics produced more rapid elimination of pulmonary bacterial burdens than conventional chemotherapy suggesting that this form of treatment could shorten the conventional treatment. PMID- 27553406 TI - Comparative study of enzymatic activities of new KatG mutants from low- and high level isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. AB - Resistance to isoniazid (INH-R) in Mycobacterium tuberculosis is mainly due to mutations at position 315 (S315T) of the catalase-peroxidase KatG. We identified 16 mutations (including 13 biochemically uncharacterized mutations) in KatG from INH-R clinical isolates of M. tuberculosis showing mutations other than S315T. The KatG enzymatic activities (catalase, peroxidase, free radical production and isonicotinoyl-NAD formation) of wild-type KatG and the 16 mutants were determined and correlated to their spatial location in a KatG model structure. Of all mutations studied, H270R, which conferred a high level of INH-R and results in the disruption of a coordination bond with the heme, caused complete loss of all enzymatic KatG activities. The mutants generally associated with a very high level of INH-R were all characterized by a drastic reduction in catalase activity and a marked decrease in INH activation activities. One mutant, A162E, displayed a behavior similar to S315T, i.e. a moderate decrease in catalase activity and a drastic decrease in the formation of the radical form of INH. Finally, the mutants associated with a low level of INH-R showed a moderate reduction in the four catalytic activities, likely stemming from an overall alteration of the folding and/or stability of the KatG protein. PMID- 27553407 TI - Discriminative expression of whole blood genes in HIV patients with latent and active TB in Ethiopia. AB - BACKGROUND: Transcriptomic host biomarkers could assist in developing effective diagnostics, vaccines and therapeutics for tuberculosis (TB). However, different biomarkers may be discriminatory in different populations depending on the host and bacillary genetics and HIV infection, and need to be addressed. METHODS: The expression levels of 45 genes that are known to be involved in or affected by TB pathogenesis were analyzed using dual color Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) assay in whole blood of 106 HIV positive individuals including active TB patients (TB(+)HIV(+), n = 29), and non TB patients that are tuberculin skin test positive (TST+) (TST(+)HIV(+), n = 26), or TST negative (TST(-)HIV(+), n = 51). RESULTS: Between the two clinical groups (TB(+)HIV(+) vs. TST(-)HIV(+)) 8 genes were differently expressed (CCL19, CD14, CD8A, FPR1, IL7R, CCL22, TNFRSF1A, and FCGR1A); between TB(+)HIV(+) vs. TST(+)HIV(+), 6 genes (CD14, IL7R, TIMP2, CCL22, TNFRSF1A, and FCGR1A) were differently expressed. Since no difference in gene expression was revealed between TST(+)HIV(+) vs. TST(-)HIV(+), we clustered both the TST(+)HIV(+) and TST(-)HIV(+) individuals as one group (TST(+/-)HIV(+)) and compared gene expression with TB(+)HIV(+) patients. Thus, the results revealed that the levels of five genes (CD8A, TIMP2, CCL22, FCGR1A and TNFRSF1A) were the most accurate single gene markers for differentiation between TB(+)HIV(+) and TST(+/-)HIV(+), with AUCs of 0.71, 0.71, 0.79, 0.83 and 0.73, respectively. However, the combination of two genes (CCL22 + FCGR1A) and FCGR1A alone were the most accurate marker for differentiation between the two groups (TB(+)HIV(+) and TST(+/ )HIV(+)) with AUC of 0.85 and 0.83, respectively. CONCLUSIONS: We showed that five genes (CD8A, TIMP2, CCL22, FCGR1A and TNFRSF1A), specifically FCGR1A and CCL22 have the potential to discriminate active TB from non-active TB in HIV patients in Ethiopia and could be used to improve diagnostic tools for active TB in HIV patients, and to understand the pathogenesis of TB/HIV coinfection. PMID- 27553408 TI - MmpL transporter-mediated export of cell-wall associated lipids and siderophores in mycobacteria. AB - Mycobacteria produce a large variety of surface-exposed lipids with unusual structures. Some of these compounds are ubiquitously present in mycobacteria and play an important role in the structural organization of the cell envelope, while others are species-specific. The biosynthesis of most of these lipids requires modular polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS) that are intracellular, suggesting that the assembly of these compounds takes place in the cytosolic compartment or near the inner leaflet of the plasma membrane. The molecular mechanisms that mediate the export of these lipid components across the cell envelope remain poorly understood. Mycobacterial membrane protein Large (MmpL) transporters, a subclass of Resistance-Nodulation Cell Division (RND) transporters, appear to play a major role in this process, acting as scaffold proteins that couple lipid synthesis and transport. Recent studies have shown that this family of transporters also contributes to siderophore secretion in Mycobacterium tuberculosis. The goal of this review is to provide the most recent advances in our understanding of the molecular mechanisms involved in lipid and siderophore transport mediated by MmpL transporters. PMID- 27553409 TI - In-depth analysis of the genome sequence of a clinical, extensively drug resistant Mycobacterium bovis strain. AB - Although human-to-human transmission of Mycobacterium bovis strains and other members of the animal lineage of the tubercle bacilli is a rare event, an extensively drug resistant (XDR) strain, named M. bovis B strain, caused a lethal outbreak in the nineties in Spain. The genome of M. bovis B strain was re sequenced by SOLiD platform and mapped to the reference M. bovis AF2122/97. The genetic polymorphisms detected have been analysed in depth. One hundred and fifty eight specific non-synonymous SNPs were detected; ninety-two of these were non conservative. In addition, one specific 3195-bp insertion could be identified as an ABC transporter gene by homology with tbd2 gene, which was found to be present in other clinical M. bovis strains. Its peculiar phenotype profile of resistance was explained by molecular characteristics, including a 5685-bp specific deletion that revealed a novel polymorphism associated with resistance to paraminosalicilic acid. From a phylogenetical point of view, according to the SNPs detected, M. bovis B could be included into the clonal complex M. bovis European 2. This is the first time that a deep analysis of the whole-genome sequencing of an extensively drug-resistant M. bovis strain is detailed. It offers the explanation for the resistance and found several data to be incorporated for future research. PMID- 27553410 TI - Virulence, biochemistry, morphology and host-interacting properties of detergent free cultured mycobacteria: An update. AB - The culturing of mycobacteria is a standard procedure that is consistent world wide, with little variation in the growth media constituents, particularly those found in liquid and solid media. Before the 1940s however, the aggregating nature of mycobacteria as well as the characteristic slow growth-rate saw mycobacterial research delay considerably. Dubos and colleagues addressed both these issues and observed that a very small volume of Tween detergent was sufficient to greatly improve the culturing of mycobacteria. Over the years however, evidence of the unfavourable effects of this detergent on a number of morphological, biochemical, pathogenic and host-interacting properties of mycobacteria surfaced. For the first time we bring together literature, past and present to comprehensively review the mycobacterial properties which are, and are not affected by the use of this detergent. We also address other detergents and methods which may circumvent the need to include Tween compounds in mycobacterial culture media. PMID- 27553412 TI - TBDRUGS - Database of drugs for tuberculosis. PMID- 27553411 TI - Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls. AB - BACKGROUND: Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB. METHOD: We isolated PBMC from smear positive TB patients (TB, N = 13) before and after treatment, latent TB infected participants (LTBI, N = 8), and healthy endemic controls (EC, N = 9) and evaluated the frequency of different populations of Tregs and expression of FOXP3 by flowcytometry using six markers. RESULTS: The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4(+)CD25(+/hi) T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4(+)CD25(+)FOXP3(+)CD127(lo) Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naive subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4(+)CD25(+)FOXP3(+)CD127(lo)CD45RO(+)Ki-67(+)) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO(+)Ki-67(-)) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5-21.9) of Tregs to 9.3% (7.0 12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection. PMID- 27553413 TI - A snapshot of the predominant single nucleotide polymorphism cluster groups of Mycobacterium tuberculosis clinical isolates in Delhi, India. AB - Several attempts have been made to associate phylogenetic differences among Mycobacterium tuberculosis strains to variations in the clinical outcome of the disease and to drug resistance. We genotyped 139 clinical isolates of M. tuberculosis obtained from patients of pulmonary tuberculosis in North Delhi region. The isolates were analyzed using nine Single nucleotide polymorphism (SNP) markers, spoligotyping and MIRU-VNTRs; and the results were correlated with their drug susceptibility profile. Results of SNP cluster group (SCG) analysis (available for 138 isolates) showed that the most predominant cluster was SCG 3a, observed in 58.7% (81/138) of the isolates with 44.4% (36/81) of these being drug susceptible, while 16% (13/81) were multidrug resistant (MDR). Of the ancestral cluster SCG 1 observed in 19.5% (27/138) of the isolates, 14.8% (4/27) were MDR while 44.4% (12/27) were drug susceptible. SCG 2 formed 5.79% (8/138) of the isolates and 50% (4/8) of these were multidrug resistant (MDR). Spoligotyping subdivided the strains into 45 shared types (n = 125) and 14 orphan strains. The orphan strains were mostly associated with SCG 3a or SCG 1, reflecting the principal SCGs found in the Indian population. SCG 1 and SCG 2 genotypes were concordant with the East African Indian (EAI) and Beijing families respectively. Central Asian (CAS) clade and its sublineages were predominantly associated with SCG 3a. No consistent association was seen between the SCGs and Harlem, T or X clades. The 15 loci MIRU-VNTR typing revealed 123/136 isolates to be unclustered, while 13 isolates were present in 6 clusters of 2-3 isolates each. However, correlating the cluster analysis with patient details did not suggest any evidence of recent transmission. In conclusion, though our study revealed the preponderance of SCG 1 and 3a in the M. tuberculosis population circulating in the region, the diversity of strains highlights the changes occurring within lineages and reemphasizes the importance of cluster investigations in extended studies. PMID- 27553414 TI - Immunoglobulin G response to mammalian cell entry 1A (Mce1A) protein as biomarker of active tuberculosis. AB - Cell wall components are major determinants of virulence of Mycobacterium tuberculosis and they contribute to the induction of both humoral and cell mediated immune response. The mammalian cell entry protein 1A (Mce1A), in the cell wall of M. tuberculosis, mediates entry of the pathogen into mammalian cells. Here, we examined serum immunoglobulin levels (IgA, IgM and total IgG) against Mce1A as a potential biomarker for diagnosis and monitoring tuberculosis (TB) treatment response. Serum samples of 39 pulmonary TB patients and 65 controls (15 healthy household contacts, 19 latently infected household contacts, 13 non-TB and 18 leprosy patients) were screened by ELISA. The median levels of all immunoglobulin classes were significantly higher in TB patients when compared with control groups. The positive test results for IgA, IgM and total IgG were 62, 54 and 82%, respectively. For comparison, routine sputum smear examination diagnosed only 26 (67%) of 39 TB cases. Sensitivities of IgA, IgM and IgG test were 59, 51.3 and 79.5%, respectively, while the specificities observed were 77.3, 83.3 and 84.4%, respectively. A significant decrease compared with baseline was also shown after TB treatment. These results suggest that circulating total IgG antibody to Mce1A could be a complementary tool to diagnosis pulmonary TB. PMID- 27553415 TI - Sputum is a surrogate for bronchoalveolar lavage for monitoring Mycobacterium tuberculosis transcriptional profiles in TB patients. AB - Pathogen-targeted transcriptional profiling in human sputum may elucidate the physiologic state of Mycobacterium tuberculosis (M. tuberculosis) during infection and treatment. However, whether M. tuberculosis transcription in sputum recapitulates transcription in the lung is uncertain. We therefore compared M. tuberculosis transcription in human sputum and bronchoalveolar lavage (BAL) samples from 11 HIV-negative South African patients with pulmonary tuberculosis. We additionally compared these clinical samples with in vitro log phase aerobic growth and hypoxic non-replicating persistence (NRP-2). Of 2179 M. tuberculosis transcripts assayed in sputum and BAL via multiplex RT-PCR, 194 (8.9%) had a p value <0.05, but none were significant after correction for multiple testing. Categorical enrichment analysis indicated that expression of the hypoxia responsive DosR regulon was higher in BAL than in sputum. M. tuberculosis transcription in BAL and sputum was distinct from both aerobic growth and NRP-2, with a range of 396-1020 transcripts significantly differentially expressed after multiple testing correction. Collectively, our results indicate that M. tuberculosis transcription in sputum approximates M. tuberculosis transcription in the lung. Minor differences between M. tuberculosis transcription in BAL and sputum suggested lower oxygen concentrations or higher nitric oxide concentrations in BAL. M. tuberculosis-targeted transcriptional profiling of sputa may be a powerful tool for understanding M. tuberculosis pathogenesis and monitoring treatment responses in vivo. PMID- 27553416 TI - Micrococcin P1 - A bactericidal thiopeptide active against Mycobacterium tuberculosis. AB - The lack of proper treatment for serious infectious diseases due to the emergence of multidrug resistance reinforces the need for the discovery of novel antibiotics. This is particularly true for tuberculosis (TB) for which 3.7% of new cases and 20% of previously treated cases are estimated to be caused by multi drug resistant strains. In addition, in the case of TB, which claimed 1.5 million lives in 2014, the treatment of the least complicated, drug sensitive cases is lengthy and disagreeable. Therefore, new drugs with novel targets are urgently needed to control resistant Mycobacterium tuberculosis strains. In this manuscript we report the characterization of the thiopeptide micrococcin P1 as an anti-tubercular agent. Our biochemical experiments show that this antibiotic inhibits the elongation step of protein synthesis in mycobacteria. We have further identified micrococcin resistant mutations in the ribosomal protein L11 (RplK); the mutations were located in the proline loop at the N-terminus. Reintroduction of the mutations into a clean genetic background, confirmed that they conferred resistance, while introduction of the wild type RplK allele into resistant strains re-established sensitivity. We also identified a mutation in the 23S rRNA gene. These data, in good agreement with previous structural studies suggest that also in M. tuberculosis micrococcin P1 functions by binding to the cleft between the 23S rRNA and the L11 protein loop, thus interfering with the binding of elongation factors Tu and G (EF-Tu and EF-G) and inhibiting protein translocation. PMID- 27553417 TI - Dissecting host factors that regulate the early stages of tuberculosis infection. AB - Incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days. Production of cytokines and chemokines in culture supernatants was monitored at various times, and the resulting temporal profiles were examined for possible correlations with either granuloma formation, or bacterial growth. While a positive association of TNF-alpha and IFN-gamma secretion levels with extent of granuloma formation could clearly be identified, we were, however, unable to detect any statistically significant relationship between any cytokine/chemokine and bacterial growth. Examination of specific host cellular biochemical pathways revealed that either modulation of neutral lipid homeostasis through inhibition of the Gi-protein coupled receptor GPR109A, or regulation of host metabolic pathways through addition of vitamin D, provided a more effective means of controlling infection. A subsequent genotypic analysis for a select subset of genes belonging to pathways known to be significant for TB pathology revealed associations of polymorphisms with cytokine secretions and bacterial growth independently. Collectively therefore, the present study supports that key metabolic pathways of the host cell, rather than levels of relevant cytokines/chemokines might be more critical for regulating the intracellular mycobacterial load, in the context of granuloma formation. PMID- 27553418 TI - Loop-mediated isothermal amplification (LAMP) assay for speedy diagnosis of tubercular lymphadenitis: The multi-targeted 60-minute approach. AB - INTRODUCTION: Tuberculous lymphadenitis (TBLA), the most common presentation of tuberculosis, poses a significant diagnostic challenge in the developing countries. Timely, accurate and cost-effective diagnosis can decrease the high morbidity associated with TBLA especially in resource-poor high-endemic regions. The loop-mediated isothermal amplification assay (LAMP), using two targets, was evaluated for the diagnosis of TBLA. MATERIAL AND METHODS: LAMP assay using 3 sets of primers (each for IS6110 and MPB64) was performed on 170 fine needle aspiration samples (85 confirmed, 35 suspected, 50 control cases of TBLA). Results were compared against IS6110 PCR, cytology, culture and smear. RESULTS: The overall sensitivity and specificity of LAMP assay, using multi-targeted approach, was 90% and 100% respectively in diagnosing TBLA. The sensitivity of multi-targeted LAMP, only MPB64 LAMP, only IS6110 LAMP and IS6110 PCR was 91.7%, 89.4%, 84.7% and 75.2%, respectively among confirmed cases and 85.7%, 77.1%, 68.5% and 60%, respectively among suspected cases of TBLA. Additional 12/120 (10%) cases were detected using multi-targeted method. DISCUSSION: The multi targeted LAMP, with its speedy and reliable results, is a potential diagnostic test for TBLA in low-resource countries. PMID- 27553419 TI - Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study. AB - Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naive adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine related serious adverse event (hypersensitivity in a tuberculosis-treated M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. PMID- 27553420 TI - Preoperative oral polymeric diet enriched with transforming growth factor-beta 2 (Modulen) could decrease postoperative morbidity after surgery for complicated ileocolonic Crohn's disease. AB - OBJECTIVE: Exclusive polymeric diet enriched with transforming growth factor-beta 2 (ANS-TGF-beta2) has been used for remission induction and maintenance in pediatric Crohn's disease (CD). Its use in the preoperative setting has never been evaluated. The aim of this study was to evaluate preoperative ANS-TGF-beta2 to decrease postoperative complications after surgery for complicated ileocolonic CD. METHODS: From 2011 to 2015, data of all consecutive patients who underwent elective surgery for ileocolonic CD were collected prospectively. Preoperative, exclusive ANS-TGF-beta2 was administered in high-risk patients with complicated CD. Complicated CD was defined by the presence of obstructive symptoms, and/or steroid treatment, and/or preoperative weight loss >10% and/or perforating CD. Outcomes of high-risk patients receiving preoperative ANS-TGF-beta2 were compared to those of low-risk patients with no complicated CD who underwent upfront surgery. RESULTS: Fifty-six patients underwent surgery for ileocolonic CD. Among them, 35 high-risk patients received preoperative ANS-TGF-beta2 and 21 low-risk patients underwent upfront surgery. Preoperative full-dose ANS-TGF-beta2 was feasible in 34/35 high-risk patients. Discontinuation of steroids during preoperative ANS-TGF-beta2 could be achieved in 10/16 patients (62.5%). Postoperative complications rates were 8/35 (23.8%) and 5/21 (22.9%) in high-risk and low-risk patients, respectively (p = 1). Temporary ileocolostomy rates in high-risk patients and in low-risk patients were 4/35 (11%) and 0/21, respectively (p = 0.286) Conclusion: Preoperative ANS-TGF-beta2 is feasible in most high-risk patients with complicated ileocolonic CD and could limit the deleterious effects of risk factors of postoperative morbidity. These results need to be confirmed in a large randomized controlled trial. PMID- 27553421 TI - Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study. AB - BACKGROUND: Epidemiological and observational studies have established that high density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1 ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C. METHOD: Serum IF1 levels were measured in 577 male participants with stable CAD (age 45-74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths. RESULTS: IF1 levels were positively correlated with HDL-C (r s = 0.40; P < 0.001) and negatively with triglycerides (r s = -0.21, P < 0.001) and CAD severity documented by the Gensini score (r s = -0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38-0.89 and 0.50 (0.28-0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (>=0.42 mg/L, P < 0.02). CONCLUSIONS: We investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy. PMID- 27553422 TI - Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene. AB - Shwachman-Diamond syndrome (SDS) (OMIM 260400) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, skeletal, and hematological abnormalities and bone marrow (BM) dysfunction. Mutations in the SBDS gene cause SDS. Clonal chromosome anomalies are often present in BM, i(7)(q10) and del(20q) being the most frequent ones. We collected 6 SDS cases with del(20q): a cluster of imprinted genes, including L3MBTL1 and SGK2 is present in the deleted region. Only the paternal allele is expressed for these genes. Based on these data, we made the hypothesis that the loss of this region, in relation to parental origin of deletion, may be of relevance for the hematological phenotype. By comparing hematological data of our 6 cases with a group of 20 SDS patients without evidence of del(20q) in BM, we observed a significant difference for Hb levels (P < 0.012), and a difference slightly above the significance level for RBC counts (P < 0.053): in both cases the values were higher in patients with del(20q). We also report preliminary evidence for an increased number of BFU-E colonies in cases with paternal deletion, data on the presence of the deletion in colonies and in mature circulating lymphocytes. (c) 2016 Wiley Periodicals, Inc. PMID- 27553424 TI - Tumours in white suckers from Lake Michigan tributaries: pathology and prevalence. AB - The prevalence and histopathology of neoplastic lesions were assessed in white sucker Catostomus commersonii captured at two Lake Michigan Areas of Concern (AOCs), the Sheboygan River and Milwaukee Estuary. Findings were compared to those observed at two non-AOC sites, the Root and Kewaunee rivers. At each site, approximately 200 adult suckers were collected during their spawning migration. Raised skin lesions were observed at all sites and included discrete white spots, mucoid plaques on the body surface and fins and large papillomatous lesions on lips and body. Microscopically, hyperplasia, papilloma and squamous cell carcinoma were documented. Liver neoplasms were also observed at all sites and included both hepatocellular and biliary tumours. Based on land use, the Kewaunee River was the site least impacted by human activities previously associated with fish tumours and had significantly fewer liver neoplasms when compared to the other sites. The proportion of white suckers with liver tumours followed the same patterns as the proportion of urban land use in the watershed: the Milwaukee Estuary had the highest prevalence, followed by the Root, Sheboygan and Kewaunee rivers. The overall skin neoplasm (papilloma and carcinoma) prevalence did not follow the same pattern, although the percentage of white suckers with squamous cell carcinoma exhibited a similar relationship to land use. Testicular tumours (seminoma) were observed at both AOC sites but not at the non-AOC sites. Both skin and liver tumours were significantly and positively associated with age but not sex. PMID- 27553423 TI - Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation. AB - BACKGROUND: The heat shock transcriptional response is essential to effective cellular function under stress. This is a highly heritable trait but the nature and extent of inter-individual variation in heat shock response remains unresolved. METHODS: We determined global transcription profiles of the heat shock response for a panel of lymphoblastoid cell lines established from 60 founder individuals in the Yoruba HapMap population. We explore the observed differentially expressed gene sets following heat shock, establishing functional annotations, underlying networks and nodal genes involving heat shock factor 1 recruitment. We define a multivariate phenotype for the global transcriptional response to heat shock using partial least squares regression and map this quantitative trait to associated genetic variation in search of the major genomic modulators. RESULTS: A comprehensive dataset of differentially expressed genes following heat shock in humans is presented. We identify nodal genes downstream of heat shock factor 1 in this gene set, notably involving ubiquitin C and small ubiquitin-like modifiers together with transcription factors. We dissect a multivariate phenotype for the global heat shock response which reveals distinct clustering of individuals in terms of variance of the heat shock response and involves differential expression of genes involved in DNA replication and cell division in some individuals. We find evidence of genetic associations for this multivariate response phenotype that involves trans effects modulating expression of genes following heat shock, including HSF1 and UBQLN1. CONCLUSION: This study defines gene expression following heat shock for a cohort of individuals, establishing insights into the biology of the heat shock response and hypotheses for how variation in this may be modulated by underlying genetic diversity. PMID- 27553425 TI - Ultrastructural Changes and Methylation of Human Oocytes Vitrified at the Germinal Vesicle Stage and Matured in vitro after Thawing. AB - AIM: The study aimed to assess the effect of in vitro vitrification and maturation on the nuclear configuration, cytoplasmic maturation and global DNA methylation pattern of human germinal vesicle (GV) stage oocytes. METHODS: Human oocytes from infertile women were randomly assigned to one of 3 groups: (i) metaphase II (MII) oocytes matured in vivo (vivo-MII, n = 56) as controls; (ii) MII oocytes matured in vitro (vitro-MII, n = 106); and (iii) MII oocytes that were vitrified at the GV stage, warmed and matured in vitro (cryo-MII, n = 122). All MII oocytes were fixed and immunofluorescence staining for spindle, chromosome, mitochondrion and cortical granules (CGs) were performed; examination was done using immunofluorescence laser scanning confocal microscope. The expression of 5-methycytosine in these MII oocytes was also assessed. RESULTS: No significant difference was observed between vitro-MII and cryo-MII groups with respect to oocyte maturation rate (72.4 vs. 78.3%). No significant differences were observed in the distribution of mitochondria, migration of CG and global DNA methylation pattern among the 3 study groups. However, the abnormal configuration of spindle and chromosome was significantly higher in cryo-MII group (78.9 and 84.2%) as compared to that in the vitro-MII (45.0 and 50.0%, p < 0.05) and vivo MII groups (27.3 and 36.4%, p < 0.05). CONCLUSION: GV oocytes appeared to resist vitrification and retain their potential for maturation to MII stage oocytes after thawing. However, GV oocytes vitrification combined with in vitro maturation could affect the organization of spindle and chromosome. PMID- 27553426 TI - Timing of interfering events in one-trial serial overshadowing of a taste aversion. AB - This set of experiments examined the question of when a stimulus would be most effective in overshadowing the acquisition of long-delay taste aversion learning. In Experiment 1 rats drank sucrose, the target solution, followed by a hydrochloric acid (HCl) solution before lithium injection some time later; HCl was presented either early or late in the interval. The late condition produced greater overshadowing than the early condition. The importance of the HCl injection interval was confirmed by Experiment 2, in which the sucrose-injection interval was varied. Experiment 3 found that even placement in a different context - an event that normally produces little overshadowing of a CTA - produced one-trial overshadowing of a sucrose aversion as long as the context was novel and exposure to it occurred immediately before lithium injection. No current theoretical account of one-trial overshadowing predicts that a late event produces more overshadowing than an early event. This result can, however, be accommodated within a modified version of the Rescorla-Wagner model. PMID- 27553427 TI - FastProject: a tool for low-dimensional analysis of single-cell RNA-Seq data. AB - BACKGROUND: A key challenge in the emerging field of single-cell RNA-Seq is to characterize phenotypic diversity between cells and visualize this information in an informative manner. A common technique when dealing with high-dimensional data is to project the data to 2 or 3 dimensions for visualization. However, there are a variety of methods to achieve this result and once projected, it can be difficult to ascribe biological significance to the observed features. Additionally, when analyzing single-cell data, the relationship between cells can be obscured by technical confounders such as variable gene capture rates. RESULTS: To aid in the analysis and interpretation of single-cell RNA-Seq data, we have developed FastProject, a software tool which analyzes a gene expression matrix and produces a dynamic output report in which two-dimensional projections of the data can be explored. Annotated gene sets (referred to as gene 'signatures') are incorporated so that features in the projections can be understood in relation to the biological processes they might represent. FastProject provides a novel method of scoring each cell against a gene signature so as to minimize the effect of missed transcripts as well as a method to rank signature-projection pairings so that meaningful associations can be quickly identified. Additionally, FastProject is written with a modular architecture and designed to serve as a platform for incorporating and comparing new projection methods and gene selection algorithms. CONCLUSIONS: Here we present FastProject, a software package for two-dimensional visualization of single cell data, which utilizes a plethora of projection methods and provides a way to systematically investigate the biological relevance of these low dimensional representations by incorporating domain knowledge. PMID- 27553429 TI - The wording and examples given in Rule 47a of the International Code of Nomenclature of Prokaryotes are misleading. AB - Rule 47a of the International Code of Nomenclature of Prokaryotes contains wording that is misleading. The examples given also give the wrong impression with regards the role of genus names in determining the priority of names at a higher taxonomic rank. PMID- 27553428 TI - Pressure dependency of localization degree in heavy fermion CeIn3: A density functional theory analysis. AB - Two dramatic discrepancies between previous reliable experimental and ab initio DFT results are identified to occur at two different pressures in CeIn3, as discussed through the paper. We physically discuss sources of the phenomena and indicate how to select an appropriate functional for a given pressure. We show that these discrepancies are due to the inaccuracy of the DFT + U scheme with arbitrary Ueff and that hybrid functionals can provide better agreement with experimental data at zero pressure. The hybrid B3PW91 approach provides much better agreement with experimental data than the GGA + U. The DFT + U scheme proves to be rather unreliable since it yields completely unpredictable oscillations for the bulk modulus with increasing values of Ueff. Our B3PW91 results show that the best lattice parameter (bulk modulus) is obtained using a larger value of alpha parameter, 0.4 (0.3 or 0.2), than that of usually considered for the AFM phase. We find that for hybrid functionals, the amount of non-local exchange must first be calibrated before conclusions are drawn. Therefore, we first systematically optimize the alpha parameter and using it investigate the magnetic and electronic properties of the system. We present a theoretical interpretation of the experimental results and reproduce them satisfactorily. PMID- 27553430 TI - Systemic Sclerosis and Kaposi's Sarcoma with Pulmonary Involvement: An Unexpected Association. PMID- 27553431 TI - Diaphragm Dysfunction in Mechanically Ventilated Patients. AB - Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi organ failure. Although the specific etiology of process is unknown, the muscle presents oxidative stress and mitochondrial changes. These cause changes in protein turnover, resulting in atrophy and impaired contractility, and leading to impaired functionality. The term 'ventilator-induced diaphragm dysfunction' was first coined by Vassilakopoulos et al. in 2004, and this phenomenon, along with injury cause by over-distention of the lung and barotrauma, represents a challenge in the daily life of ventilated patients. Diaphragmatic dysfunction affects prognosis by delaying extubation, prolonging hospital stay, and impairing the quality of life of these patients in the years following hospital discharge. Ultrasound, a non-invasive technique that is readily available in most ICUs, could be used to diagnose this condition promptly, thus preventing delays in starting rehabilitation and positively influencing prognosis in these patients. PMID- 27553433 TI - Editorial. PMID- 27553432 TI - Olaparib does not cause clinically relevant QT/QTc interval prolongation in patients with advanced solid tumours: results from two phase I studies. AB - BACKGROUND: Some therapeutic agents in oncology can be causally associated with specific cardiovascular events including QT/QTc interval prolongation. We investigated the effect of multiple dosing of the oral poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib (tablet formulation) on QT/QTc interval. METHODS: Two phase I, open-label, three-part studies (NCT01921140 [study 4] and NCT01900028 [study 7]) were conducted in adults with refractory/resistant advanced solid tumours. In both studies, parts A and B assessed the QT/QTc interval effects of single-dose oral olaparib 100 (study 4) or 300 (study 7) mg and multiple-dose olaparib 300 mg bid for 5 days, respectively, while part C evaluated continued access to olaparib for additional safety analyses. An ANCOVA model tested the primary objective of multiple-dose effects of olaparib on QT interval corrected using Fridericia's formula (QTcF). RESULTS: Data from 119 and 109 patients were pooled from parts A and B, respectively, for QT/QTc analysis. At pre-dose and up to 12 h post-dose, the upper limits of the 90 % confidence intervals (CIs) for the difference in QTcF least squares means after olaparib multiple dosing versus control (day -1) were <10 ms, suggesting a lack of clinically relevant effect on cardiac repolarization. A slight shortening of QTcF was observed at most time points versus control. QTcF results for the individual studies and single-dose olaparib paralleled the primary multiple-dose pooled analysis, with upper limits of the 90 % CIs < 10 ms. CONCLUSION: Olaparib tablets administered as multiple or single doses had no clinically significant effect on QT/QTc interval. PMID- 27553434 TI - Editorial. PMID- 27553435 TI - Prognostic factors from a randomized phase III trial of paclitaxel and carboplatin versus paclitaxel and cisplatin in metastatic or recurrent cervical cancer: Japan Clinical Oncology Group (JCOG) trial: JCOG0505-S1. AB - PURPOSE: The Japan Clinical Oncology Group (JCOG) trial JCOG0505 demonstrated the statistically significant non-inferiority of paclitaxel plus carboplatin (TC) to paclitaxel plus cisplatin (TP) in terms of overall survival (OS) in metastatic or recurrent cervical cancer. In that trial, patients were randomly assigned, adjusting for institution and known prognostic factors. The objective of this ancillary study was to evaluate the appropriateness of the adjustment factors used to have randomly assigned treatments and to investigate new potentially useful prognostic factors of paclitaxel plus platinum for future randomized trials in metastatic or recurrent cervical cancer. METHODS: The study subjects comprised 244 eligible patients in the JCOG0505 who were merged to have received either TC or TP. The effects of the following factors on OS were investigated using a Cox regression model taking into consideration the adjustment factors used in randomization in this trial (e.g., performance status [PS]) and other baseline factors, including platinum-free interval (PFI), pretreatment hemoglobin levels (PHLs), and pretreatment platelet counts (PPCs). RESULTS: The median follow-up was 17.6 months, and median OS was 18.0 months. The hazard ratio was 1.83 in patients with a PS of 1 or 2 (vs. 0; P = 0.0004; 95 % confidence interval [CI] 1.31-2.55), 2.92 in patients with a PFI of <6 months (vs. PFI of >=12 months; P < 0.0001; 95 % CI 1.73-4.91), 2.09 in patients with a PFI of <12 months (vs. PFI of >=12 months; P = 0.0034; 95 % CI 1.28-3.44), and 0.69 in patients with PHL higher than or equal to the median value (vs. less than the median; P = 0.016; 95 % CI 0.51-0.93). No significant differences were obtained for PPC or the other known factors. CONCLUSIONS: In addition to the known prognostic factor of PS, which was used as an adjusting factor, a PFI of <12 months and lower PHL were newly demonstrated to be associated with poor outcomes in patients with metastatic or recurrent cervical cancer. These new prognostic factors should be validated in future prospective trials. CLINICAL TRIAL INFORMATION: UMIN-CTR[ http://www.umin.ac.jp/ctr/ ] ID: C000000335. PMID- 27553437 TI - Marie Stopes abortion services suspended after safety concerns. PMID- 27553436 TI - Early prediction of outcome after severe traumatic brain injury: a simple and practical model. AB - BACKGROUND: Traumatic brain injury (TBI) is a heterogeneous syndrome with a broad range of outcome. We developed a simple model for long-term outcome prognostication after severe TBI. METHODS: Secondary data analysis of a large multicenter randomized trial. Patients were grouped according to 6-month extended Glasgow outcome scale (eGOS): poor-outcome (eGOS <= 4; severe disability or death) and acceptable outcome (eGOS > 4; no or moderate disability). A prediction decision tree was built using binary recursive partitioning to predict poor or acceptable 6-month outcome. Comparison to two previously published and validated models was made. RESULTS: The decision tree included the predictors of head Abbreviated Injury Scale (AIS) severity, the Marshall computed tomography score, and pupillary reactivity. All patients with a head AIS severity of 5 were predicted to have a poor outcome. In patients with head AIS severity < 5, the model predicted an acceptable outcome for (1) those with Marshall score of 1, and (2) those with Marshall score above 1 but with reactive pupils at admission. The decision tree had a sensitivity of 72.3 % (95 % CI: 66.4-77.6 %) and specificity of 62.5 % (95 % CI: 54.9-69.6 %). The proportion correctly classified for the comparison models was similar to our model. Our model was more apt at correctly classifying those with poor outcome but more likely to misclassify those with acceptable outcome than the comparison models. CONCLUSION: Predicting long-term outcome early after TBI remains challenging and inexact. This model could be useful for research and quality improvement studies to provide an early assessment of injury severity, but is not sufficiently accurate to guide decision making in the clinical setting. PMID- 27553438 TI - Dorso-medial and ventro-lateral functional specialization of the human retrosplenial complex in spatial updating and orienting. AB - The retrosplenial complex is a region within the posterior cingulate cortex implicated in spatial navigation. Here, we investigated the functional specialization of this large and anatomically heterogeneous region using fMRI and resting-state functional connectivity combined with a spatial task with distinct phases of spatial 'updating' (i.e., integrating and maintaining object locations in memory during spatial displacement) and 'orienting' (i.e., recalling unseen locations from current position in space). Both spatial 'updating' and 'orienting' produced bilateral activity in the retrosplenial complex, among other areas. However, spatial 'updating' produced slightly greater activity in ventro lateral portions, of the retrosplenial complex, whereas spatial 'orienting' produced greater activity in a more dorsal and medial portion of it (both regions localized along the parieto-occipital fissure). At rest, both ventro-lateral and dorso-medial subregions of the retrosplenial complex were functionally connected to the hippocampus and parahippocampus, regions both involved in spatial orientation and navigation. However, the ventro-lateral subregion of the retrosplenial complex displayed more positive functional connectivity with ventral occipital and temporal object recognition regions, whereas the dorso medial subregion activity was more correlated to dorsal activity and frontal activity, as well as negatively correlated with more ventral parietal structures. These findings provide evidence for a dorso-medial to ventro-lateral functional specialization within the human retrosplenial complex that may shed more light on the complex neural mechanisms underlying spatial orientation and navigation in humans. PMID- 27553439 TI - Antioxidant activity and total phenolic and flavonoids content variations of leaves extracts of white Horehound (Marrubium vulgare Linne) from three geographical origins. AB - OBJECTIFS: To elucidate the effect of the sampling location of Marrubium vulgare L. leaves on phenolic contents and antioxidant proprieties of flavonoids extracts. MATERIALS AND METHODS: M. vulgare L. leaves were collected from three different geographical locations belonging to northwest Algeria: Tessala (mountain region), M'sila forest (coastal region), and Ain Skhouna (steppe region). The flavonoid extraction was achieved using organic solvents with different polarities (methanol, chloroform, ethyl acetate, and hexane). Folin Ciocalteu colorimetric method was used for quantification of total phenolic contents, and aluminum chloride assay for quantification of total flavonoid contents. The antioxidant properties of flavonoids extract were studied by free l,l-diphenyl-2-picrylhydrazyl radical-scavenging technique. RESULTS: Total phenolic and flavonoids concentrations varied respectively between 40.7 and 160mg gallic acid equivalents/g and 27.4 and 66.3mg catechin equivalents/g. The DPPH free radical-scavenging activity shows that the antioxidant activity of the flavonoid extracts varied significantly (P<0.001) depending on the type of the organic solvent used, and the sampling location. The methanol, chloroform and ethyl acetate extracts exhibited the highest percentages of inhibition unlike to the aqueous and hexane extracts. These percentages are ranged from 54.8 to 98.8% at 1000MUg/mL. In general, M'sila forest flavonoids extracts showed the highest free radical inhibition capacity; followed by those of Ain Skhouna and Tessala Mountain. The inhibitory concentration 50 (IC50) ranged from 33.7 to 774MUg/mL and often exceeded those recorded by phenolic standards (ascorbic acid, gallic acid, caffeic acid, tannic acid and catechin). The phytochemical screening revealed the presence of some flavonoid classes, such as flavans and flavanols. CONCLUSION: The results suggested a potent antioxidant activity of M. vulgare flavonoids extracts, which may find its application in feature research for the food and the pharmacological industries. PMID- 27553440 TI - Imbalanced functional link between reward circuits and the cognitive control system in patients with obsessive-compulsive disorder. AB - Altered reward processing and cognitive deficits are often observed in patients with obsessive-compulsive disorder (OCD); however, whether the imbalance in activity between reward circuits and the cognitive control (CC) system is associated with compulsive behavior remains unknown. Sixty-eight OCD patients and 33 cognitively normal (CN) healthy subjects participated in this resting-state functional magnetic resonance imaging study. Alterations in the functional connectivity between reward circuits and the CC system were quantitatively assessed and compared between the groups. A Granger causality analysis was used to determine the causal informational influence between and within reward circuits and the CC system across all subjects. OCD patients showed a dichotomous pattern of enhanced functional coupling in their reward circuits and a weakened functional coupling in their CC system when compared to CN subjects. Neural correlates of compulsive behavior were primarily located in the reward circuits and CC system in OCD patients. Importantly, the CC system exerted a reduced interregional causal influence over the reward system in OCD patients relative to its effect in CN subjects. The limitations of this study are that it was a cross sectional study and the potential effects of environmental and genetic factors were not explored. OCD patients showed an imbalance in the functional link between reward circuits and the CC system at rest. This bias toward a loss of control may define a pathological state in which subjects are more vulnerable to engaging in compulsive behaviors. PMID- 27553441 TI - Positive affect and sleep: A systematic review. AB - A sizeable literature has implicated sleep in the phenomenological experience of various mood disorders, vulnerability to psychopathology, and overall poor psychological functioning. By contrast, positive affective states (e.g., joy, happiness, vigor, positive mood) that may contribute to sleep have been understudied. This systematic review integrates findings from cross-sectional, longitudinal, ambulatory, and experimental studies that investigate the association between positive affect and sleep. A comprehensive search for all available research on the topic was performed in three electronic bibliographic databases (PubMed, PsycINFO, CINAHL). Two independent reviewers extracted data on study characteristics and quality. From 10,853 retrieved articles, 44 fulfilled inclusion criteria and formed the base of the review. The majority of studies (68.2%, n = 30) were classified as weak or having high risk of bias. In general, the pattern of findings suggests that aggregate or trait measures provide the most consistent evidence of an association between positive affect and sleep in healthy populations. More limited empirical data exist on the association between positive affect and sleep in clinical populations. We conclude that more rigorous and theoretically informed research is needed before firm conclusions can be drawn about the possible beneficial impact of positive affect on sleep outcomes. PMID- 27553442 TI - Patient-controlled bolus femoral nerve block after knee arthroplasty: quadriceps recovery, analgesia, local anesthetic consumption. AB - BACKGROUND: Continuous femoral nerve block (cFNB) induces quadriceps muscle weakness, but patient-controlled femoral nerve block (PCFNB) can provide analgesia with lower consumption of local anesthetics compared to cFNB. We hypothesized that cFNB followed by PCFNB leads to accelerated recovery of quadriceps weakness after total knee arthroplasty compared to cFNB alone. Secondary outcomes were local anesthetic consumption, pain, and mobilization. METHODS: Fifty-six subjects received post-operative cFNB for 24 h and then randomized to receive either cFNB (basal infusion of 6 ml/h using a dummy bolus button; n = 27) or PCFNB (bolus infusion of 3 ml with a lockout time of 30 min and no basal infusion; n = 29) using 0.08% levobupivacaine for the subsequent 24 h in a double-blind manner (registration: UMIN000010105). Quadriceps strength was assessed using a hand-held dynamometer. The percentage change from baseline was compared between groups. RESULTS: Quadriceps strength at 48 h was 47.3 +/- 18.3% in the cFNB group and 49.7 +/- 15.7% in the PCFNB group (95% confidence interval 7.0-11.9%, P = 0.61). Local anesthetic consumption during the post-operative period was significantly lower in the PCFNB group compared to the cFNB group (102 +/- 10.8 ml vs.146 +/- 4.6 ml; P < 0.001). No significant differences were found in any of the other outcomes, including pain scores at rest and during knee rehabilitation. CONCLUSION: Continuous femoral nerve block followed by PCFNB does not improve quadriceps strength recovery time compared to cFNB alone after total knee arthroplasty, but similar analgesic effects were demonstrated with reduced levobupivacaine consumption. PMID- 27553443 TI - Obesity Management in Europe: Current Status and Objectives for the Future. AB - OBJECTIVE: This study aims at assessing the status of obesity management in the European region and identifying future goals and objectives of professionals working in the field of obesity. METHODS: Presidents of all 31 EASO-affiliated (EASO = European Association for the Study of Obesity) national associations for the study of obesity were asked to invite 5 obesity experts from their country to participate in a survey. A total of 74 obesity professionals out of 23 countries participated. Questions addressed the development of guidelines, the status of obesity management, and goals and objectives for the future in obesity management. Further, EASO's three vice-presidents participated in in-depth, semi structured interviews, in which they were asked to provide their reflection on the survey data. RESULTS: Most countries define obesity as a clinical and chronic disease, but various differences in obesity management standards exist across Europe. Existing guidelines mainly focus on the acute treatment of obesity rather than on long-term approaches. CONCLUSION: Multidisciplinary approaches for obesity management and the collaboration between general practitioners and hospitals as well as between professionals at the local level and networks of obesity management centers need to be improved across Europe. Good practices and evidence are available. PMID- 27553444 TI - Fracture risk in people with developmental disabilities: results of a large claims data analysis. AB - : Age- and sex-specific fracture rates of 18,000 people with developmental disabilities aged 0-69 years were compared to the general population. Age standardized incidence of femoral fracture was 4.8- and 7.1-fold higher in women and men, respectively. Comparable fracture risks to the general population occurred 10-15 years earlier in females and 20-40 years earlier in males. INTRODUCTION: Previous studies suggested that fracture risks in people with developmental disabilities (DD) may be higher than in people in the general population. However, there are no current sufficiently large studies to compare age- and sex-specific fracture rates of single fracture types. METHODS: People with DD and incident fractures were identified by routine data of a health insurance company. Fractures in the general population were derived from the official fracture statistics. Age-specific and age-standardized fracture incidences were analyzed. To compare fracture risks in people with DD with that of the general population incidence ratios were calculated. RESULTS: Between 2008 and 2010, 148 femoral fractures and 469 other fractures were observed in nearly 18,000 people with DD aged 0-69 years. The three most frequent fracture types leading to hospital admission were fractures of the femur, lower leg/ankle, and shoulder/arm. For femoral fractures, a particularly high risk was observed in children and adolescents with DD. In adults with DD, the risk of femoral fractures increased with increasing age. Even if the youngest age category was not considered, the age-standardized incidence was 4.8- and 7.1-fold higher in women and men, respectively. For all other fracture types, except fractures of forearm/hand and of pelvis, people with DD had also higher fracture incidences than the general population. CONCLUSIONS: People with DD have a high fracture burden. Comparable risks of femoral fracture, for example, occurred about 10-15 years earlier in females and even 20-40 years earlier in males with DD than in the general population. PMID- 27553446 TI - An analysis of the most common types of hand injury mistakes and their cost in the acute setting. AB - This study aimed to explore the most common hand injury errors occurring in Emergency Departments in England. A Freedom of Information request was made to the NHS Litigation Authority for claims data related to hand injuries in English Emergency Departments from 2004 to 2014. All successful hand injury claims against an individual DGH ED were also analysed. Two hundred and eighteen successful claims were made, costing a total of L6,273,688.22. Diagnosis error was the most common successful claim (97). Four successful claims were brought against the Emergency Department. Causes of error included the use of inappropriate views and failure to correlate imaging with clinical findings. Hand injury diagnostic error has been the most common cause of successful litigious claims against Emergency Departments over the past 10 years. This paper demonstrates that fracture recognition and clinical diagnosis of hand injuries are key areas to target to reduce error rates. PMID- 27553445 TI - Fractures in spina bifida from childhood to young adulthood. AB - : This study assessed the prevalence and types of fractures in spina bifida and examined risk factors for fracture. Fracture prevalence was highest in childhood and reduced in adolescence and young adulthood. The importance of maintaining mobility is highlighted by the increased risk of fracture in those who are non ambulatory. INTRODUCTION: The aims of this study are to study the prevalence and types of fractures according to age group in spina bifida and examine risk factors associated with fracture. METHODS: This is a retrospective cohort study of 146 individuals with spina bifida aged 2 years or older who attended the paediatric or adult spina bifida multidisciplinary clinic at a single tertiary hospital. RESULTS: Median age at which first fracture occurred was 7 years (interquartile range 4-13 years). Fracture rates in children (ages 2-10), adolescents (ages 11-18) and adults (age > 18) were 10.9/1000 (95 % confidence interval 5.9-18.3), 5.4/1000 (95 % CI 1.5-13.8) and 2.9/1000 (95 % CI 0.6-8.1) patient years respectively. Childhood fractures predominantly involved the distal femur and femoral shaft; these fractures were rarely seen in adulthood. Non ambulatory status was associated with a 9.8 times higher risk of fracture compared with ambulatory patients (odds ratio 9.8, p = 0.016, 95 % CI 1.5-63.0). Relative risk of re-fracture was 3.1 (95 % CI 1.4-6.8). Urological intervention with intestinal segments was associated with renal calculi (p = 0.037) but neither was associated with fracture. CONCLUSIONS: The risk of fracture is lower in adults compared with children with spina bifida. The predominant childhood fracture affects the distal femur, and immobility is the most significant risk factor for fracture. Clinical factors contributing to fracture risk need to be elucidated to enable selection of patients who require investigation and treatment of osteoporosis. PMID- 27553447 TI - Infective endocarditis due to multiple species of anaerobes following tricuspid valve replacement. PMID- 27553448 TI - Effects of implementation of an online comprehensive antimicrobial-stewardship program in ICUs: A longitudinal study. AB - BACKGROUND/PURPOSE: The long-term effects of antimicrobial-stewardship programs in the intensive care units (ICUs) have not been adequately examined. We evaluated the impact of an online comprehensive antimicrobial stewardship program (OCASP) on the outcomes of patients in 200-bed medical/surgical ICUs over the course of 11 years. METHODS: We analyzed the records of adult patients admitted to ICUs during the 5 years before (n = 27,499) and the 6 years after (n = 33,834) implementation of an OCASP. Antimicrobial consumption, expenditures, duration of treatment, incidence of healthcare-associated infections (HAIs), prevalence of HAIs caused by antimicrobial-resistant strains, and crude or sepsis-related mortality of patients were analyzed. Segmented regression analyses of interrupted time series were used to assess the significance of changes in antimicrobial use. RESULTS: Compared to the patients in the pre-OCASP period, the patients in the post-OCASP period were older, had greater disease severity, longer ICU stays, and were more likely to receive antimicrobials, but had lower antimicrobial expenditures and crude and sepsis-related mortality. The trend of overall antimicrobial use [slope of defined daily dose/1000 patient-days vs. time) increased significantly before OCASP implementation (p < 0.001), but decreased significantly after implementation (p < 0.01). The administration duration of all classes of antibiotics were significantly shorter (p < 0.001) and the incidences of HAIs were significantly lower (p < 0.001) after implementation. However, there was an increase in the proportion of HAIs caused by carbapenem-resistant Acinetobacter baumannii relative to all A. baumannii infections. CONCLUSION: Implementation of an OCASP in the ICUs reduced antimicrobial consumption and expenditures, but did not compromise healthcare quality. PMID- 27553449 TI - Carbapenem-resistant Acinetobacter baumannii mediastinitis after aortic graft implantation successfully treated by adjunctive gentian violet irrigation and antibiotic combination therapy. PMID- 27553450 TI - Laboratory investigation of a suspected outbreak caused by Providencia stuartii with intermediate resistance to imipenem at a long-term care facility. AB - BACKGROUND: Providencia stuartii survives well in natural environment and often causes opportunistic infection in residents of long-term care facilities (LTCFs). Clinical isolates of P. stuartii are usually resistant to multiple antibiotics. The bacterium is also naturally resistant to colistin and tigecycline. Treatment of infections caused by carbapenem-resistant P. stuartii is challenging. METHODS: During a 15-month period in 2013-2014, four isolates (P1, P2, and P3B/P3U) of P. stuartii showing intermediate resistance to imipenem were identified at a regional hospital in southern Taiwan. They were identified from three patients (P1-P3) transferred from the same LTCF for the treatment of the infection. Pulsed field gel electrophoresis was used to genotype the isolates. Resistance genes/plasmids and outer membrane proteins were investigated by polymerase chain reaction and sequence analysis. RESULTS: Isolates P1 and P3B/P3U demonstrated similar pulsotypes. All isolates were found to have resistance genes (blaCMY-2, qnrD1, aac(6')-Ib-cr) carried on nonconjugative IncA/C plasmids of different sizes. A single point mutation was identified in the chromosomal gyrA (Ser83Ile) and parC (Ser84Ile) genes of all isolates. Various point mutations and insertion/deletion changes were found in their major outer membrane protein gene ompPst1. CONCLUSIONS: Isolates of similar pulsotypes could appear after 15 months and caused urosepsis in another resident of the same LTCF. The bacterium may have persisted in the environment and caused opportunistic infection. As LTCF residents are usually vulnerable to infections, surveillance of multidrug resistant organisms and infection control intervention that have been established in acute-care hospitals to control infections by resistant organisms are apparently as essential in LTCFs. PMID- 27553451 TI - MgrB variants in colistin-susceptible and colistin-resistant Klebsiella pneumoniae ST258. AB - Resistance determinants of a colistin susceptible and five colistin resistant Klebsiella pneumoniae ST258 from a Hungarian outbreak were investigated. A novel MgrB variant in colistin susceptible strain was found. Elevated phoP and arn gene expressions and wild-type PmrB in all colistin resistant K. pneumoniae were detected. All strains lacked mcr-1. PMID- 27553453 TI - The effect of neighborhood size on effective population size in theory and in practice. AB - The distinction between the effective size of a population (Ne) and the effective size of its neighborhoods (Nn) has sometimes become blurred. Ne reflects the effect of random sampling on the genetic composition of a population of size N, whereas Nn is a measure of within-population spatial genetic structure and depends strongly on the dispersal characteristics of a species. Although Nn is independent of Ne, the reverse is not true. Using simulations of a population of annual plants, it was found that the effect of Nn on Ne was well approximated by Ne=N/(1-FIS), where FIS (determined by Nn) was evaluated population wide. Nn only had a notable influence of increasing Ne as it became smaller (?16). In contrast, the effect of Nn on genetic estimates of Ne was substantial. Using the temporal method (a standard two-sample approach) based on 1000 single-nucleotide polymorphisms (SNPs), and varying sampling method, sample size (2-25% of N) and interval between samples (T=1-32 generations), estimates of Ne ranged from infinity to <0.1% of the true value (defined as Ne based on 100% sampling). Estimates were never accurate unless Nn and T were large. Three sampling techniques were tested: same-site resampling, different-site resampling and random sampling. Random sampling was the least biased method. Extremely low estimates often resulted when different-site resampling was used, especially when the population was large and the sample fraction was small, raising the possibility that this estimation bias could be a factor determining some very low Ne/N that have been published. PMID- 27553452 TI - Estimating contemporary effective population size in non-model species using linkage disequilibrium across thousands of loci. AB - Contemporary effective population size (Ne) can be estimated using linkage disequilibrium (LD) observed across pairs of loci presumed to be selectively neutral and unlinked. This method has been commonly applied to data sets containing 10-100 loci to inform conservation and study population demography. Performance of these Ne estimates could be improved by incorporating data from thousands of loci. However, these thousands of loci exist on a limited number of chromosomes, ensuring that some fraction will be physically linked. Linked loci have elevated LD due to limited recombination, which if not accounted for can cause Ne estimates to be downwardly biased. Here, we present results from coalescent and forward simulations designed to evaluate the bias of LD-based Ne estimates ([Ncirc ]e). Contrary to common perceptions, increasing the number of loci does not increase the magnitude of linkage. Although we show it is possible to identify some pairs of loci that produce unusually large r(2) values, simply removing large r(2) values is not a reliable way to eliminate bias. Fortunately, the magnitude of bias in [Ncirc ]e is strongly and negatively correlated with the process of recombination, including the number of chromosomes and their length, and this relationship provides a general way to adjust for bias. Additionally, we show that with thousands of loci, precision of [Ncirc ]e is much lower than expected based on the assumption that each pair of loci provides completely independent information. PMID- 27553454 TI - Effective population size in ecology and evolution. PMID- 27553455 TI - Long-term effective population size dynamics of an intensively monitored vertebrate population. AB - Long-term genetic data from intensively monitored natural populations are important for understanding how effective population sizes (Ne) can vary over time. We therefore genotyped 1622 common buzzard (Buteo buteo) chicks sampled over 12 consecutive years (2002-2013 inclusive) at 15 microsatellite loci. This data set allowed us to both compare single-sample with temporal approaches and explore temporal patterns in the effective number of parents that produced each cohort in relation to the observed population dynamics. We found reasonable consistency between linkage disequilibrium-based single-sample and temporal estimators, particularly during the latter half of the study, but no clear relationship between annual Ne estimates () and census sizes. We also documented a 14-fold increase in between 2008 and 2011, a period during which the census size doubled, probably reflecting a combination of higher adult survival and immigration from further afield. Our study thus reveals appreciable temporal heterogeneity in the effective population size of a natural vertebrate population, confirms the need for long-term studies and cautions against drawing conclusions from a single sample. PMID- 27553456 TI - Evaluation of newly-developed aniseikonia testing method based on space eikonometry. AB - BACKGROUND: We have developed a new aniseikonia testing method based on the space eikonometry (ATSE) principle. The purpose of this study was to compare aniseikonia obtained by the ATSE to that of the conventional new aniseikonia tests (NAT), which is commonly used in Japan. METHODS: Thirty normal subjects (mean age: 22.8 years) without ocular disease except for refractive errors were studied. All of the subjects had normal binocular single vision with stereopsis. We excluded subjects with refractive errors greater than 1.00 D cylinder or anisometropia (spherical equivalent) greater than 1.00 D. We simulated overall aniseikonia of five and 10 per cent with afocal size lenses (HOYA, Tokyo, Japan) placed in the optical path of the fully corrected right eye. We measured aniseikonia three times with either the ATSE or NAT and the averages were used for the statistical analyses. RESULTS: The mean and standard deviation (SD) of aniseikonia determined by the ATSE was 5.1 +/- 0.8 per cent with the five per cent afocal lens and 10.1 +/- 0.8 per cent with the 10 per cent afocal lens. Aniseikonia was 2.8 +/- 1.3 per cent with the five per cent afocal lens and 6.0 +/- 2.5 per cent with the 10 per cent afocal lens by the NAT. The mean error was + two per cent of the theoretical value by the ATSE and -42 per cent by the NAT for both afocal lenses. CONCLUSION: We recommend the use of the new ATSE for quantitative determination of aniseikonia, as it is more accurate than the NAT. PMID- 27553457 TI - Synergistic effects of the chitosan addition and polysaccharides-EPS on the formation of anaerobic granules. AB - Concomitant early granulation with chitosan addition under a syntroph-specific substrate and enhancement of extracellular polymeric substances (EPS) production were aimed at to build anaerobic granules with high syntrophic activities in a short period. Two laboratory-scale upflow anaerobic sludge blanket reactors were operated as control (R1) and chitosan addition (R2) reactors during early granulation (phase 1). Chitosan decreased the negativity of microbial surface charges (zeta potential) to -10.5 mV on day 58 which led to increases in average diameter sizes, nuclei and granule ratio of approximately 115 um, 55.1% and 8.2%, respectively. While zeta potential in R1 slightly changed, this resulted in less microbial aggregation. Although microbial aggregation in R2 was rapidly triggered by chitosan addition during phase 1, its structure was clumpy with rough surface due to lack of EPS. Substrate switching to glucose increased polysaccharides-EPS during phase 2 which was synergistically improved on the structural characteristics of microbial aggregate in R2, that is, more spherical and compact, with a smoother surface. Rapid-growth microorganism was also boosted, which then dominated the outer layer of the aggregate. The Archaea clumps were observed at a deeper layer and were surrounded by Eubacteria, presumably acetogens, indicating a syntrophic relationship due to substrate association between these microbial groups. PMID- 27553458 TI - Charge density waves in disordered media circumventing the Imry-Ma argument. AB - Two powerful theoretical predictions, Anderson localization and the Imry-Ma argument, impose significant restrictions on the phases of matter that can exist in the presence of even the smallest amount of disorder in one-dimensional systems. These predictions forbid electrically conducting states and ordered states respectively. It was thus remarkable that a mechanism to circumvent Anderson localization relying on the presence of correlated disorder was found, that is also realized in certain biomolecular systems. In a similar manner, we show that the Imry-Ma argument can be circumvented, resulting in the formation of stable ordered states with discrete broken symmetries in disordered one dimensional systems. We then investigate other mechanisms by which disorder can destroy an ordered state. PMID- 27553459 TI - The Role of Existential Beliefs Within the Relation of Centenarians' Health and Well-Being. AB - The purpose of this study was to explore the role of existential beliefs in mediating the influence of health on centenarians' well-being. A total of 80 centenarians (mean age 101.1; SD = 1.3; 81.3 % women) with no/minor cognitive impairment were included. The OARS questionnaire for diseases and functional capacity (ADL, IADL), the Satisfaction with Life Scale, and the existential beliefs subscale were used for data collection. The findings suggest that existential resources are a crucial element for mitigating the impact of health constraints in subjective well-being in this population. Appropriate models of intervention for very old age that recognize the importance of religion, spirituality, and meaning of life are to be considered. PMID- 27553461 TI - Identification of virulence genes in Vibrio spp. isolates from the 2009 Bermuda reef fish mortality event. PMID- 27553460 TI - Cardiac implantable electronic device infection due to Mycobacterium species: a case report and review of the literature. AB - BACKGROUND: Infection of cardiac implantable electronic devices is a serious cardiovascular disease and it is associated with a high mortality. Mycobacterium species may rarely cause cardiac implantable electronic devices infection. CASE PRESENTATION: We are reporting a case of miliary tuberculosis in an Arab patient with dilated cardiomyopathy and a cardiac resynchronization therapy-defibrillator device that was complicated with infection of his cardiac resynchronization therapy-defibrillator device. To our knowledge, this is the third case in the literature with such a presentation and all patients died during the course of treatment. This underscores the importance of early diagnosis and management. We also performed a literature review of reported cases of cardiac implantable electronic devices infection related to Mycobacterium species. CONCLUSIONS: Cardiac implantable electronic devices infection due to Mycobacterium species is an uncommon but a well-known entity. Early diagnosis and prompt management may result in a better outcome. PMID- 27553462 TI - Letter From the Editors. PMID- 27553463 TI - Letter From the Guest Editor. PMID- 27553464 TI - Bifunctional Gallium-68 Chelators: Past, Present, and Future. AB - This article reviews the development of bifunctional chelates for synthesising (68)Ga radiopharmaceuticals. It structures the chelates into groups of macrocycles, nonmacrocycles, and chimeric derivatives. The most relevant bifunctional chelates are discussed in chelate structure, parameters of (68)Ga labeling, and stability of the (68)Ga-chelate complexes. Furthermore those derivatives are included, where (67)Ga was applied instead of (68)Ga. A particular feature discussed is the ability of certain bifunctional chelate structures to function in kit-type preparation of the (68)Ga radiopharmaceuticals. Currently, nonmacrocyclic and chimeric derivates attract particular attention such as THP-derivates and DATA-derivates. PMID- 27553465 TI - Advances in the Diagnosis of Neuroendocrine Neoplasms. AB - Somatostatin receptor PET/CT using (68)Ga-labeled somatostatin analogs, is a mainstay for the evaluation of the somatostatin receptor status in neuroendocrine neoplasms. In addition, the assessment of glucose metabolism by (18)F-FDG PET/CT at diagnosis can overcome probable shortcomings of histopathologic grading. This offers a systematic theranostic approach for the management of neuroendocrine neoplasms, that is, patient selection for the appropriate treatment-surgery, somatostatin analogs, peptide receptor radionuclide therapy, targeted therapies like everolimus and sunitinib, or chemotherapy-and also for therapy response monitoring. Novel targets, for example, the chemokine receptor CXCR4 in higher grade tumors and glucagon like peptide-1 receptor in insulinomas, appear promising for imaging. Scandium-44 and Copper-64, especially on account of their longer half-life (for pretherapeutic dosimetry) and cyclotron production (which favors mass production), might be the potential alternatives to (68)Ga for PET/CT imaging. The future of molecular imaging lies in Radiomics, that is, qualitative and quantitative characterization of tumor phenotypes in correlation with tumor genomics and proteomics, for a personalized cancer management. PMID- 27553466 TI - Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer. AB - The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. PMID- 27553467 TI - Angiogenesis Imaging Using (68)Ga-RGD PET/CT: Therapeutic Implications. AB - Angiogenesis imaging is important for diagnostic and therapeutic treatment of various malignant and nonmalignant diseases. The Arg-Gly-Asp (RGD) sequence has been known to bind with the alphavbeta3 integrin that is expressed on the surface of angiogenic blood vessels or tumor cells. Thus, various radiolabeled derivatives of RGD peptides have been developed for angiogenesis imaging. Among the various radionuclides, (68)Ga was the most widely studied for RGD peptide imaging because of its excellent nuclear physical properties, easy-to-label chemical properties, and cost-effectiveness owing to the availability of a (68)Ge (68)Ga generator. Thus, various (68)Ga-labeled RGD derivatives have been developed and applied for preclinical and clinical studies. Clinical trials were performed for both malignant and nonmalignant diseases. Breast cancer, glioma, and lung cancer were malignant, and myocardial infarction, atherosclerosis, and moyamoya disease were nonmalignant among the investigated diseases. Further, these (68)Ga-labeled RGD derivatives could be applied to assess the effects of antiangiogenic treatment or theragnosis or both, of cancers. In conclusion, the angiogenesis imaging technology using (68)Ga-labeled RGD derivatives might be useful for the development of new therapeutic assessments, and for diagnostic and theragnostic applications. PMID- 27553468 TI - (68)Ga PET Ventilation and Perfusion Lung Imaging-Current Status and Future Challenges. AB - Gallium-68 ((68)Ga) is a positron-emitting radionuclide suitable for positron emission tomography (PET) imaging that has a number of convenient features-it has a physical half life of 68 minutes, it is generator produced at the PET facility and needs no local cyclotron, and being a radiometal is able to be chelated to a number of useful molecules for diagnostic imaging with PET. (68)Ga has recently been investigated as a radiotracer for ventilation and perfusion (V/Q) lung imaging. It is relatively easy to produce both V/Q radiopharmaceuticals labeled with (68)Ga for PET studies, it offers higher spatial resolution than equivalent SPECT studies, the short half life allows for multiple (repeated) scans on the same day, and low amounts of radiotracer can be used thus limiting the radiation dose to the subject. In the usual clinical setting requiring a V/Q scan, that of suspected pulmonary embolism, the role of (68)Ga V/Q PET may be limited from a logistical perspective, however, in nonacute applications such as lung function evaluation, radiotherapy treatment planning, and respiratory physiology investigations it would appear to be an ideal modality to employ. PMID- 27553469 TI - Gallium-68 PET: A Powerful Generator-based Alternative to Infection and Inflammation Imaging. AB - The process of inflammation (with or without infection) forms part of essentially every major debilitating disease. Early detection and accurate distinction of inflammation from infection are important to optimize and individualize therapy. Nuclear medicine is ideally suited for the detection of pathologic changes early on and is able to target a magnitude of role players involved in the aforementioned processes. Hybrid modalities such as PET/CT and PET/MRI offer high spatial resolution that combines morphologic and pathophysiological changes and add various quantification possibilities that are preferable in these settings. It follows then that the development of PET radiopharmaceuticals is imperative to make use of these latest advances. Gallium-68 (Ga-68)-based tracers are exceptionally well suited to these indications, considering the year-round availability from a single generator, the relative cost-effectiveness, and relative ease of labeling. Over the past few years, the development of Ga-68 based tracers has understandably exploded with a recent growing interest in infection and inflammation imaging. This review aims to highlight some of the most important and interesting advances made with Ga-68-based PET/CT in the field of infection and inflammation imaging. PMID- 27553470 TI - Gallium-68 EDTA PET/CT for Renal Imaging. AB - Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 ((68)Ga) EDTA PET usage predates Technetium-99m ((99m)Tc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in (68)Ga owing to the greater availability of PET technology and use of (68)Ga to label other radiotracers. (68)Ga EDTA can be used a substitute for (99m)Tc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the (68)Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed (68)Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for (99m)Tc DTPA if unavailable owing to supply issues, and have additionally examined the role of (68)Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function. PMID- 27553471 TI - Renal Function Assessment During Peptide Receptor Radionuclide Therapy. AB - Theranostics labeled with Y-90 or Lu-177 are highly efficient therapeutic approaches for the systemic treatment of various cancers including neuroendocrine tumors and prostate cancer. Peptide receptor radionuclide therapy (PRRT) has been used for many years for metastatic or inoperable neuroendocrine tumors. However, renal and hematopoietic toxicities are the major limitations for this therapeutic approach. Kidneys have been considered as the "critical organ" because of the predominant glomerular filtration, tubular reabsorption by the proximal tubules, and interstitial retention of the tracers. Severe nephrotoxity, which has been classified as grade 4-5 based on the "Common Terminology Criteria on Adverse Events," was reported in the range from 0%-14%. There are several risk factors for renal toxicity; patient-related risk factors include older age, preexisting renal disease, hypertension, diabetes mellitus, previous nephrotoxic chemotherapy, metastatic lesions close to renal parenchyma, and single kidney. There are also treatment-related issues, such as choice of radionuclide, cumulative radiation dose to kidneys, renal radiation dose per cycle, activity administered, number of cycles, and time interval between cycles. In the literature, nephrotoxicity caused by PRRT was documented using different criteria and renal function tests, from serum creatinine level to more accurate and sophisticated methods. Generally, serum creatinine level was used as a measure of kidney function. Glomerular filtration rate (GFR) estimation based on serum creatinine was preferred by several authors. Most commonly used formulas for estimation of GFR are "Modifications of Diet in Renal Disease" (MDRD) equation and "Cockcroft-Gault" formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51 ethylenediaminetetraacetic acid (EDTA), or measurement of Tc-99m-MAG3 clearance, particularly in patients with preexisting risk factors for long-term nephrotoxicity. Proximal tubular reabsorption and interstitial retention of tracers result in excessive renal irradiation. Coinfusion of positively charged amino acids, such as l-lysine and l-arginine, is recommended to decrease the renal retention of the tracers by inhibiting the proximal tubular reabsorption. Furthermore, nephrotoxicity may be reduced by dose fractionation. Patient specific dosimetric studies showed that renal biological effective dose of <0Gy was safe for patients without any risk factors. A renal threshold value <28Gy was recommended for patients with risk factors. Despite kidney protection, renal function impairment can occur after PRRT, especially in patients with risk factors and high single or cumulative renal absorbed dose. Therefore, patient specific dosimetry may be helpful in minimizing the renal absorbed dose while maximizing the tumor dose. In addition, close and accurate renal function monitoring using more precise methods, rather than plasma creatinine levels, is essential to diagnose the early renal functional changes and to follow-up the renal function during the treatment. PMID- 27553472 TI - Muscle Strength and Body Weight Mediate the Relationship Between Physical Activity and Usual Gait Speed. AB - BACKGROUND: Usual gait speed (UGS) is recognized as a good indicator of a variety of health conditions as well as a predictor of future disability and mortality. There is evidence that UGS increases with physical activity. Muscle function and body composition changes may mediate these changes. However, we do not know exactly which of these factors contribute to the effect of physical activity on gait speed or the magnitude of their contribution. METHODS: Data are from 1378 women aged 75 years and older recruited in the Toulouse EPIDemiologie de l'OSteoporose cohort. Body weight and composition (dual energy X-ray absorptiometry), knee extension strength, and physical activity habits were assessed. The INDIRECT macro for SPSS (SPSS Inc, Chicago, IL) was used to determine total and specific indirect effects of physical activity on UGS through body weight (BW) and composition as well as muscle mass and strength. RESULTS: Knee extension strength [95% confidence interval (CI) 0.0091, 0.0231] and BW (95% CI 0.0037, 0.0412), but not fat mass or muscle mass, were mediators of the relationship between physical activity and gait speed. However, muscle mass significantly mediated the relationship between physical activity and muscle strength (95% CI -3.0722, -0.6265). CONCLUSIONS: Results suggest that muscle strength and BW are the most significant mediators of the relationship between physical activity and UGS. Although the specific effect of muscle mass appears negligible at first sight, its role should not be overlooked given its impact on muscle strength. PMID- 27553473 TI - Corrigendum to "Overlapping and distinct brain regions involved in estimating the spatial position of numerical and non-numerical magnitudes: An fMRI study" [Neuropsychologia 51 (2013) 979-989]. PMID- 27553474 TI - Mitochondrial fatty acid synthesis, fatty acids and mitochondrial physiology. AB - Mitochondria and fatty acids are tightly connected to a multiplicity of cellular processes that go far beyond mitochondrial fatty acid metabolism. In line with this view, there is hardly any common metabolic disorder that is not associated with disturbed mitochondrial lipid handling. Among other aspects of mitochondrial lipid metabolism, apparently all eukaryotes are capable of carrying out de novo fatty acid synthesis (FAS) in this cellular compartment in an acyl carrier protein (ACP)-dependent manner. The dual localization of FAS in eukaryotic cells raises the questions why eukaryotes have maintained the FAS in mitochondria in addition to the "classic" cytoplasmic FAS and what the products are that cannot be substituted by delivery of fatty acids of extramitochondrial origin. The current evidence indicates that mitochondrial FAS is essential for cellular respiration and mitochondrial biogenesis. Although both beta-oxidation and FAS utilize thioester chemistry, CoA acts as acyl-group carrier in the breakdown pathway whereas ACP assumes this role in the synthetic direction. This arrangement metabolically separates these two pathways running towards opposite directions and prevents futile cycling. A role of this pathway in mitochondrial metabolic sensing has recently been proposed. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum. PMID- 27553475 TI - Cardiac glycosides: From molecular targets to immunogenic cell death. AB - Cardiac glycosides (CGs) are approved for the treatment of cardiovascular alterations and their known cellular target is the alpha subunit of the sodium (Na+)/potassium (K+)-ATPase (NKA). Pharmacologically, they represent a well-known generation of drugs for treating cardiovascular problems, thus allowing the investigation of potential dose-dependent side effects. Interestingly, since the end of the 1960s, epidemiological studies have indicated that anti-cancer effects were associated with the regular use of these compounds. Since then, a large body of evidence has been accumulated on the in vitro and in vivo effects of CGs in various experimental models, thus confirming their selective action on cancer cell proliferation and viability. CGs have the potential for targeted therapeutic applications. Many of the anti-cancer activities of these compounds have been linked to the inhibition of their primary target, the NKA. A number of studies have shown a correlation between the overexpression of specific alpha subunits in cancerous versus non-cancerous cells and cancer cell responsiveness. Other findings have provided evidence of the on-target nature of the ascribed anti cancer effects. More recently, studies have indicated additional intracellular targets for these agents, whose modulation might be, at least in some instances, unrelated to NKA targeting. These include endosomal trafficking of both NKA and Src kinase, downregulation of pro-survival Mcl-1 and Bcl-xL pro-survival proteins, and immunogenic cell death induction, among others. This research update summarizes the current knowledge about CGs as new, targeted anti-cancer agents, alone or in combination with other chemotherapeutic compounds. PMID- 27553476 TI - GYY4137 ameliorates intestinal barrier injury in a mouse model of endotoxemia. AB - Intestinal barrier injury has been reported to play a vital role in the pathogenesis of endotoxemia. This study aimed to investigate the protective effect of GYY4137, a newly synthesized H2S donor, on the intestinal barrier function in the context of endotoxemia both in vitro and in vivo. Caco-2 (a widely used human colon cancer cell line in the study of intestinal epithelial barrier function) monolayers incubated with lipopolysaccharide (LPS) or TNF alpha/IFN-gamma and a mouse model of endotoxemia were used in this study. The results suggested that GYY4137 significantly attenuated LPS or TNF-alpha/IFN gamma induced increased Caco-2 monolayer permeability. The decreased expression of TJ (tight junction) proteins induced by LPS and the altered localization of TJs induced by TNF-alpha/IFN-gamma was significantly inhibited by GYY4137; similar results were obtained in vivo. Besides, GYY4137 promoted the clinical score and histological score of mice with endotoxemia. Increased level of TNF alpha/IFN-gamma in the plasma and increased apoptosis in colon epithelial cells was also attenuated by GYY4137 in mice with endotoxemia. This study indicates that GYY4137 preserves the intestinal barrier function in the context of endotoxemia via multipathways and throws light on the development of potential therapeutic approaches for endotoxemia. PMID- 27553477 TI - Characterization of the cutaneous mycobiota in healthy and allergic cats using next generation sequencing. AB - BACKGROUND: Next generation sequencing (NGS) studies have demonstrated a diverse skin-associated microbiota and microbial dysbiosis associated with atopic dermatitis in people and in dogs. The skin of cats has yet to be investigated using NGS techniques. HYPOTHESIS/OBJECTIVES: We hypothesized that the fungal microbiota of healthy feline skin would be similar to that of dogs, with a predominance of environmental fungi, and that fungal dysbiosis would be present on the skin of allergic cats. ANIMALS: Eleven healthy cats and nine cats diagnosed with one or more cutaneous hypersensitivity disorders, including flea bite, food-induced and nonflea nonfood-induced hypersensitivity. METHODS: Healthy cats were sampled at twelve body sites and allergic cats at six sites. DNA was isolated and Illumina sequencing was performed targeting the internal transcribed spacer region of fungi. Sequences were processed using the bioinformatics software QIIME. RESULTS: The most abundant fungal sequences from the skin of all cats were classified as Cladosporium and Alternaria. The mucosal sites, including nostril, conjunctiva and reproductive tracts, had the fewest number of fungi, whereas the pre-aural space had the most. Allergic feline skin had significantly greater amounts of Agaricomycetes and Sordariomycetes, and significantly less Epicoccum compared to healthy feline skin. CONCLUSIONS: The skin of healthy cats appears to have a more diverse fungal microbiota compared to previous studies, and a fungal dysbiosis is noted in the skin of allergic cats. Future studies assessing the temporal stability of the skin microbiota in cats will be useful in determining whether the microbiota sequenced using NGS are colonizers or transient microbes. PMID- 27553479 TI - The Association Between Insurance and Transfer of Noninjured Children From Emergency Departments. AB - STUDY OBJECTIVE: Among children requiring hospital admission or transfer, we seek to determine whether insurance is associated with the decision to either admit locally or transfer to another hospital. METHODS: This cross-sectional study used Healthcare Cost and Utilization Project 2012 Nationwide Emergency Department Sample. Pediatric patients receiving care in emergency departments (EDs) who were either admitted or transferred were included. Clinical Classifications Software was used to categorize patients into noninjury diagnostic cohorts. Multivariable logistic regression models adjusting for potential confounders, including severity of illness and comorbidities, and incorporating nationally representative weights were used to determine the association between insurance and the odds of transfer relative to admission. RESULTS: A total of 240,620 noninjury pediatric ED events met inclusion criteria. Patient and hospital characteristics, including older age and nonteaching hospitals, were associated with greater odds of transfer relative to admission. Patients who were uninsured or had self-pay had higher odds of transfer (odds ratio [OR] 3.84; 95% confidence interval [CI] 2.08 to 7.09) relative to admission compared with those with private insurance. Uninsured and self-pay patients also had higher odds of transfer across all 13 diagnostic categories, with ORs ranging from 2.96 to 12.00. Patients with Medicaid (OR 1.05; 95% CI 0.90 to 1.22) and other insurances (OR 1.14; 95% CI 0.87 to 1.48) had similar odds of transfer compared with patients with private insurance. CONCLUSION: Children without insurance and those considered as having self-pay are more likely to be transferred to another hospital than to be admitted for inpatient care within the same receiving hospital compared with children with private insurance. This study reinforces ongoing concerns about disparities in the provision of pediatric ED and inpatient care. PMID- 27553478 TI - Centromere inactivation on a neo-Y fusion chromosome in threespine stickleback fish. AB - Having one and only one centromere per chromosome is essential for proper chromosome segregation during both mitosis and meiosis. Chromosomes containing two centromeres are known as dicentric and often mis-segregate during cell division, resulting in aneuploidy or chromosome breakage. Dicentric chromosome can be stabilized by centromere inactivation, a process which reestablishes monocentric chromosomes. However, little is known about this process in naturally occurring dicentric chromosomes. Using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence combined with FISH (IF-FISH) on metaphase chromosome spreads, we demonstrate that centromere inactivation has evolved on a neo-Y chromosome fusion in the Japan Sea threespine stickleback fish (Gasterosteus nipponicus). We found that the centromere derived from the ancestral Y chromosome has been inactivated. Our data further suggest that there have been genetic changes to this centromere in the two million years since the formation of the neo-Y chromosome, but it remains unclear whether these genetic changes are a cause or consequence of centromere inactivation. PMID- 27553480 TI - Does Everything Need to Be "Scientific"? PMID- 27553481 TI - Is Nebulized Hypertonic Saline Solution Effective for Acute Bronchiolitis? PMID- 27553482 TI - Characteristics of and Predictors for Apnea and Clinical Interventions During Procedural Sedation. AB - STUDY OBJECTIVE: We describe the characteristics of and predictors for apnea and clinical interventions during emergency department (ED) procedural sedation. METHODS: High-resolution data were collected prospectively, using a convenience sample of ED patients undergoing propofol or ketofol sedation. End tidal CO2 (etco2), respiratory rate, pulse rate, and SpO2 were electronically recorded in 1 second intervals. Procedure times, drug delivery, and interventions were electronically annotated. Kaplan-Meier curves were used to describe the onset of clinical interventions as a function of sedation time. The onset of apnea (15 consecutive seconds with carbon dioxide <=10 mm Hg) and clinical interventions were estimated with a series of Cox proportional hazards survival models, with time to first apnea or clinical intervention as the dependent variable. Finally, we tested the association between apnea and clinical intervention. RESULTS: Three hundred twelve patients were analyzed (53% male patients). Apnea was preceded by etco2 less than 30 mm Hg or greater than 50 mm Hg at 30, 60, and 90 seconds before its onset. Clinical interventions were predicted by apnea, SpO2, and propofol use. Increasing age predicted both apnea and interventions. Apnea was not predicted by respiratory rate or SpO2. Apnea occurred in half of the patients and clinical interventions in a quarter of them. Clinical intervention was not predicted by abnormal respiratory rate or abnormal etco2 level. The majority of clinical interventions (85%) were minor, with no cases of assisted ventilation, intubation, or complications. CONCLUSION: Alterations in etco2 predicted apnea along a specific time course. Alterations in SpO2, apnea, and propofol use predicted clinical interventions. Increasing age predicted both apnea and clinical intervention. PMID- 27553483 TI - Norms of valence, arousal, concreteness, familiarity, imageability, and context availability for 1,100 Chinese words. AB - In the present study, we collected valence, arousal, concreteness, familiarity, imageability, and context availability ratings for a total of 1,100 Chinese words. The ratings for all variables were collected with 9-point Likert scales. We tested the reliability of the present database by comparing it to the extant Chinese Affective Word System, and performed split-half correlations for all six variables. We then evaluated the relationships between all variables. Regarding the affective variables, we found a typical quadratic relation between valence and arousal, in line with previous findings. Likewise, significant correlations were found between the semantic variables. Importantly, we explored the relationships between ratings for the affective variables (i.e., valence and arousal) and concreteness ratings, suggesting that valence and arousal ratings can predict concreteness ratings. This database of affective norms will be a valuable source of information for emotion research that makes use of Chinese words, and will enable researchers to use highly controlled Chinese verbal stimuli to more reliably investigate the relation between cognition and emotion. PMID- 27553484 TI - Symbolic magnitude processing in elementary school children: A group administered paper-and-pencil measure (SYMP Test). AB - The ability to compare symbolic numerical magnitudes correlates with children's concurrent and future mathematics achievement. We developed and evaluated a quick timed paper-and-pencil measure that can easily be used, for example in large scale research, in which children have to cross out the numerically larger of two Arabic one- and two-digit numbers (SYMP Test). We investigated performance on this test in 1,588 primary school children (Grades 1-6) and examined in each grade its associations with mathematics achievement. The SYMP Test had satisfactory test-retest reliability. The SYMP Test showed significant and stable correlations with mathematics achievement for both one-digit and two-digit comparison, across all grades. This replicates the previously observed association between symbolic numerical magnitude processing and mathematics achievement, but extends it by showing that the association is observed in all grades in primary education and occurs for single- as well as multi-digit processing. Children with mathematical learning difficulties performed significantly lower on one-digit comparison and two-digit comparison in all grades. This all suggests satisfactory construct and criterion-related validity of the SYMP Test, which can be used in research, when performing large-scale (intervention) studies, and by practitioners, as screening measure to identify children at risk for mathematical difficulties or dyscalculia. PMID- 27553485 TI - Toxicity of Atorvastatin on Pancreas Mitochondria: A Justification for Increased Risk of Diabetes Mellitus. AB - Statins (including atorvastatin) are a widely used class of drugs, and like all medications, they have a potential for adverse effects. Recently, it has been shown that statins also exert side effects on the pancreas. In vitro studies have suggested that this class of drugs induced a reduction in insulin secretion. Also, the use of statins is associated with a raised risk of diabetes mellitus (DM), but the mechanisms underlying statin-induced diabetes are poorly known. Literature data indicate that several statins are able to induce apoptosis signalling. This study was designed to examine the mechanism of atorvastatin on mitochondria obtained from rat pancreas. In our study, mitochondria were obtained from the pancreas and then exposed to atorvastatin and vehicle to investigate probable toxic effects. The results showed that atorvastatin (25, 50, 75, 100 and 125 MUM) increased reactive oxygen species (ROS) production, mitochondrial swelling, collapse of mitochondrial membrane potential and cytochrome c release, the orchestrating factor for mitochondria-mediated apoptosis signalling. Atorvastatin also reduced the ATP levels. These results propose that the toxicity of atorvastatin on pancreas mitochondria is a key point for drug-induced apoptotic cell loss in the pancreas and therefore a justification for increased risk of DM. PMID- 27553486 TI - N-acetylcysteine as a single therapy for sudden deafness. AB - CONCLUSION: Like NAC ameliorates hearing loss from acoustic trauma in the inner ear, NAC may also rescue hearing loss from sudden deafness confined to the inner ear. OBJECTIVE: This study assesses the effect of N-acetyl-L-cysteine (NAC) as a single therapy for sudden deafness. METHODS: Thirty-five sudden deafness patients with neither systemic disorders nor central signs in electronystagmography were treated with NAC alone and assigned to Group A. For comparison, another 35 sudden deafness patients treated by corticosteroids and plasma expander were assigned to Group B. There were no significant differences between the two groups in terms of age, sex, laterality, and pre-treatment mean hearing level. All patients underwent an inner ear test battery comprising audiometry, and ocular vestibular evoked myogenic potential (oVEMP), cervical VEMP (cVEMP), and caloric tests. RESULTS: Groups A and B did not significantly differ in the pre-treatment mean hearing level, and percentages of abnormal oVEMP, cVEMP, and caloric tests, indicating that the involvement severity of sudden deafness between the two groups was similar. However, Group A (43 +/- 27 dB) showed significantly greater mean hearing gain than Group B (21 +/- 28 dB), and Group A (91%) revealed better improved rate of hearing than Group B (57%). PMID- 27553487 TI - Two Unrelated Undervirilized 46,XY Males with Inherited NR5A1 Variants Identified by Whole-Exome Sequencing. AB - BACKGROUND: Undervirilized 46,XY males with bifid scrotum often pose a diagnostic challenge, and the majority of cases typically do not receive a genetic diagnosis. NR5A1 mutations can be seen in 10-20% of the cases and are a relatively common cause of undervirilization. METHODS: Whole-exome sequencing was utilized to study 10 undervirilized 46,XY subjects with bifid scrotum. RESULTS: Exome sequencing identified novel NR5A1 variants, both affecting exon 7, in 2 of the 10 subjects with bifid scrotum. Subject 1 had a heterozygous frameshift variant, c.1150delC, p.Leu384fsTer1, within the ligand-binding domain inherited from his unaffected father. Subject 2 had a novel splice-site variant c.1139 2T>C, affecting the canonical splice acceptor site for exon 7 and also disrupting the ligand-binding domain. Both subjects had serum testosterone levels within the normal range as infants. CONCLUSIONS: We describe two novel NR5A1 variants, demonstrating mutations in this gene as a common cause of milder cases of 46,XY undervirilization. Whole-exome sequencing results yielded the diagnosis in 2 out of 10 cases without a previous diagnosis, supporting the value of this approach. Significant genotype-phenotype variability was also noted with Subject 1's paternal inheritance from his unaffected father. PMID- 27553488 TI - Isolation studies reveal a shift in the cultivable microbiome of oak affected with Acute Oak Decline. AB - Acute Oak Decline is a syndrome within the Oak Decline complex in Britain. Profuse stem bleeding and larval galleries of the native buprestid, Agrilus biguttatus characterize the disease. A systematic study comparing healthy with diseased trees was undertaken. This work reports the result of isolations from healthy trees, diseased and non-symptomatic tissue within AOD affected trees, at five sites in England. Bacteria and fungi were identified using the DNA gyrase B gene, or ITS 1 sequencing. A significantly higher proportion of diseased tissues (82%) yielded more bacteria than either healthy (18%) or non-symptomatic tissue in diseased trees (33%). Overall bacterial community compositions varied at each site, but significant similarities were evident in diseased tissues at all sites. Enterobacteriaceae dominated in diseased trees whereas Pseudomonadaceae dominated healthy trees. Significant associations between diseased tissues and certain bacterial species occurred, implying that the cause of tissue necrosis was not due to random microbiota. Brenneria goodwinii and Gibbsiella quercinecans were key species consistently isolated from diseased tissue; Rahnella victoriana and an un-named Pseudomonas taxon were also frequently isolated from both healthy and diseased trees. Most fungi isolated were from the outer bark and had no significant association with tree health status. It was concluded that there was a shift in the cultivatable bacterial microbiome of diseased trees, with Enterobacteriaceae strongly represented in symptomatic but not healthy tissues. No single species dominated the isolations from diseased tissues and the tissue degradation in AOD is therefore likely to have a polymicrobial cause. PMID- 27553489 TI - Interpreting transcriptional changes using causal graphs: new methods and their practical utility on public networks. AB - BACKGROUND: Inference of active regulatory cascades under specific molecular and environmental perturbations is a recurring task in transcriptional data analysis. Commercial tools based on large, manually curated networks of causal relationships offering such functionality have been used in thousands of articles in the biomedical literature. The adoption and extension of such methods in the academic community has been hampered by the lack of freely available, efficient algorithms and an accompanying demonstration of their applicability using current public networks. RESULTS: In this article, we propose a new statistical method that will infer likely upstream regulators based on observed patterns of up- and down-regulated transcripts. The method is suitable for use with public interaction networks with a mix of signed and unsigned causal edges. It subsumes and extends two previously published approaches and we provide a novel algorithmic method for efficient statistical inference. Notably, we demonstrate the feasibility of using the approach to generate biological insights given current public networks in the context of controlled in-vitro overexpression experiments, stem-cell differentiation data and animal disease models. We also provide an efficient implementation of our method in the R package QuaternaryProd available to download from Bioconductor. CONCLUSIONS: In this work, we have closed an important gap in utilizing causal networks to analyze differentially expressed genes. Our proposed Quaternary test statistic incorporates all available evidence on the potential relevance of an upstream regulator. The new approach broadens the use of these types of statistics for highly curated signed networks in which ambiguities arise but also enables the use of networks with unsigned edges. We design and implement a novel computational method that can efficiently estimate p-values for upstream regulators in current biological settings. We demonstrate the ready applicability of the implemented method to analyze differentially expressed genes using the publicly available networks. PMID- 27553490 TI - Streptomyces ovatisporus sp. nov., isolated from deep marine sediment. AB - The taxonomic position of a Gram-staining-positive strain, designated strain S4702T was isolated from a marine sediment collected from the southern Black Sea coast, Turkey, determined using a polyphasic approach. The isolate was found to have chemotaxonomic, morphological and phylogenetic properties consistent with its classification as representing a member of the genus Streptomyces and formed a distinct phyletic line in the 16S rRNA gene tree. S4702T was found to be most closely related to the type strains of Streptomyces marinus(DSM 41968T; 97.8 % sequence similarity) and Streptomyces abyssalis (YIM M 10400T; 97.6 %). 16S rRNA gene sequence similarities with other members of the genus Streptomyces were lower than 97.5 %. DNA-DNA relatedness of S4702T and the most closely related strain S. marinus DSM 41968T was 21.0 %. The G+C content of the genomic DNA was 72.5 mol%. The cell wall of the strain contained l,l-diaminopimelic acid and the cell-wall sugars were glucose and ribose. The major cellular fatty acids were identified as anteiso-C15 : 0, iso-C16 : 0, anteiso-C17 : 0 and iso-C15 : 0. The predominant menaquinone was MK-9(H8). The polar lipid profile of S4702T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside. S4702T could be distinguished from its closest phylogenetic neighbours using a combination of chemotaxonomic, morphological and physiological properties. Consequently, it is proposed that S4702T represents a novel species of the genus Streptomyces, for which the name Streptomyces ovatisporus sp. nov. is proposed. The type strain is S4702T (DSM 42103T=KCTC 29206T=CGMCC 4.7357T). PMID- 27553491 TI - Predicting clinical outcomes in chordoma patients receiving immunotherapy: a comparison between volumetric segmentation and RECIST. AB - BACKGROUND: The Response Evaluation Criteria in Solid Tumors (RECIST) are the current standard for evaluating disease progression or therapy response in patients with solid tumors. RECIST 1.1 calls for axial, longest-diameter (or perpendicular short axis of lymph nodes) measurements of a maximum of five tumors, which limits clinicians' ability to adequately measure disease burden, especially in patients with irregularly shaped tumors. This is especially problematic in chordoma, a disease for which RECIST does not always adequately capture disease burden because chordoma tumors are typically irregularly shaped and slow-growing. Furthermore, primary chordoma tumors tend to be adjacent to vital structures in the skull or sacrum that, when compressed, lead to significant clinical consequences. METHODS: Volumetric segmentation is a newer technology that allows tumor burden to be measured in three dimensions on either MR or CT. Here, we compared the ability of RECIST measurements and tumor volumes to predict clinical outcomes in a cohort of 21 chordoma patients receiving immunotherapy. RESULTS: There was a significant difference in radiologic time to progression Kaplan-Meier curves between clinical outcome groups using volumetric segmentation (P = 0.012) but not RECIST (P = 0.38). In several cases, changes in volume were earlier and more sensitive reflections of clinical status. CONCLUSION: RECIST is a useful evaluation method when obvious changes are occurring in patients with chordoma. However, in many cases, RECIST does not detect small changes, and volumetric assessment was capable of detecting changes and predicting clinical outcome earlier than RECIST. Although this study was small and retrospective, we believe our results warrant further research in this area. PMID- 27553492 TI - Web-based physiotherapy for people with axial spondyloarthritis (WEBPASS) - a study protocol. AB - BACKGROUND: Evidence suggests people with axial spondyloarthritis (axial SpA) should exercise up to five times per week but lack of time, symptoms, cost and distance are barriers to regular exercise in axial SpA. Personalised exercise programmes delivered via the internet might support people with axial SpA to reach these exercise targets. The aim of this study is to investigate the effect of, and adherence to, a 12 month personalised web-based physiotherapy programme for people with axial SpA. METHODS: Fifty people with axial SpA will be recruited to this prospective, interventional cohort study. Each participant will be assessed by a physiotherapist and an individualised exercise programme set up on www.webbasedphysio.com . Participants will be asked to complete their programme five times per week for 12 months. With the exception of adherence, data will be collected at baseline, 6 and 12 months. DISCUSSION: The primary outcome measure is adherence to the exercise programme over each four week cycle (20 sessions maximum per cycle) and over the 12 months. Secondary measures include function (BASFI), disease activity (BASDAI), work impairment (WPAI:SpA), quality of life (ASQoL, EQ5D), attitude to exercise (EMI-2, EAQ), spinal mobility (BASMI), physical activity and the six minute walk test. Participants will also be interviewed to explore their adherence, or otherwise, to the intervention. This study will determine the adherence and key clinical outcomes of a targeted web based physiotherapy programme for axial SpA. This data will inform clinical practice and the development and implementation of similar programmes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02666313 , 20th January 2016. PMID- 27553493 TI - Charge state distribution studies of pure and oxygen mixed krypton ECR plasma - signature of isotope anomaly and gas mixing effect. AB - We report the charge state distributions of the pure, 25% and 50% oxygen mixed krypton plasma to shed more light on the understanding of the gas mixing and the isotope anomaly [A. G. Drentje, Rev. Sci. Instrum. 63 (1992) 2875 and Y Kawai, D Meyer, A Nadzeyka, U Wolters and K Wiesemann, Plasma Sources Sci. Technol. 10 (2001) 451] in the electron cyclotron resonance (ECR) plasmas. The krypton plasma was produced using a 10 GHz all-permanent-magnet ECR ion source. The intensities of the highly abundant four isotopes, viz. 82 Kr (~11.58%), 83 Kr (~11.49%), 84 Kr (~57%) and 86 Kr (17.3%) up to ~ +14 charge state have been measured by extracting the ions from the plasma and analysing them in the mass and the energy using a large acceptance analyzer-cum-switching dipole magnet. The influence of the oxygen gas mixing on the isotopic krypton ion intensities is clearly evidenced beyond +9 charge state. With and without oxygen mixing, the charge state distribution of the krypton ECR plasma shows the isotope anomaly with unusual trends. The anomaly in the intensities of the isotopes having quite closer natural abundance, viz. 82 Kr, 86 Kr and 83 Kr, 86 Kr is prominent, whereas the intensity ratio of 86 Kr to 84 Kr shows a weak signature of it. The isotope anomaly tends to disappear with increasing oxygen mixing in the plasma. The observed trends in the intensities of the krypton isotopes do not follow the prediction of linear Landau wave damping in the plasma. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27553494 TI - Effect of a chemical inhibitor of human phosphatidylethanolamine-binding protein 4 on radiosensitivity of rectal cancer cells. AB - BACKGROUND: Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is a well established antiapoptosis molecule in recent years. It has also been demonstrated to be involved in the radioresistance of rectal cancer. The objective of this study was to determine whether IOI-42, a chemical inhibitor of hPEBP4, could sensitize rectal cancer cells. METHODS: Rectal cancer cells were treated with IOI 42 alone or in combination with irradiation. Clonogenic survival assays and tumor volume growth analysis were used, respectively, to study the effect of IOI-42 in vitro and in vivo. Western blot was adopted to measure the activation of signal pathway. RESULTS: Clonogenic survival assays showed that IOI-42, combined with irradiation, caused a significant decrease in colony formation compared with radiation alone, which was associated with the downregulation of Akt activation. And we also confirmed the effect of IOI-42 in nude mice transplanted with human rectal cancer subcutaneously. CONCLUSIONS: These data suggest that IOI-42 has a potential to enhance the radiosensitivity of rectal cancer cells, providing a rationale to further investigate the feasibility of combining of IOI-42 with radiation, keeping in mind that this may result in unexpected toxicities. PMID- 27553495 TI - Molecular epidemiology of Staphylococcus aureus from Lambarene, Gabon. AB - While there is an abundance of data on the epidemiology and molecular typing of Staphylococcus aureus, especially those carrying Panton-Valentine leucocidin (PVL) genes or mecA from Western Europe, Northern America and Australia, comparably few studies target African strains. In this study, we characterised genes associated with virulence and resistance, as well the phylogenetic background of S. aureus from healthy carriers and outpatients in Gabon. In total, 103 isolates from 96 study participants were characterised. Seventy-nine isolates originated from throat swabs and 24 isolates from skin lesions. Three isolates carried mecA, although only one, belonging to CC8-MRSA-IV [PVL+] 'USA300', was found to be phenotypically oxacillin-resistant; two CC88-MRSA-IV isolates appeared to be oxacillin-susceptible. PVL genes were common, with a total of 44 isolates (43 %) found to be PVL-positive. CC15-MSSA [PVL+] (n = 29) and CC152 MSSA [PVL+] (n = 9) were the predominant clones among the PVL-positive isolates. Among PVL-negative isolates, CC5-MSSA (n = 12), CC101-MSSA (n = 10) and CC15 (n = 9) were the most frequent. A hitherto undescribed multilocus sequence type of S. schweitzeri was detected twice in unrelated patients. The data emphasise a need for further studies on the role of PVL in African populations and the clinical significance of S. schweitzeri. PMID- 27553496 TI - Pathogenicity of duck plague and innate immune responses of the Cherry Valley ducks to duck plague virus. AB - Duck plague caused by duck plague virus (DPV) is an acute and contagious disease. To better understand the pathogenic mechanism of duck plague virus in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DPV could replicate quickly in many tissues, leading to pathological lesions, especially on the spleen. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the brain, and the antiviral innate immune response was established, but not sufficient to restrict viral replication. In contrast, although the expression of many major pattern recognition receptors (PRRs) increased in the spleen, the expression of most cytokines was declined. Our study indicates that DPV is a pantropic virus that can replicate rapidly in tissues, causing serious pathological lesions but the immune responses are different in the spleen and brain. To our knowledge, this is the first report to systematically explore the expression profiles of the immune genes in the DPV infected ducks. Our data provide a foundation for further study of the pathogenicity of duck plague. PMID- 27553497 TI - Epidermal Growth Factor Receptor Mutations and Prognosis in Pathologic N1-N2 Pulmonary Adenocarcinoma. AB - BACKGROUND: Advanced unresectable pulmonary adenocarcinoma with the epidermal growth factor receptor (EGFR) exon 21 L858R point mutation (Ex21) is associated with a poor prognosis. However, for early-stage resectable adenocarcinoma, Ex21 tumors have a lower-grade malignancy than exon 19 deleted (Ex19) tumors. We therefore investigated the effect of EGFR mutations on the prognosis in patients with completely resected pN1-N2 adenocarcinoma. METHODS: Five-year disease-free survival (DFS) and overall survival (OS) were analyzed in 202 pN1-N2 pulmonary adenocarcinoma patients, 100 of whom had EGFR mutations, comprising Ex21 in 41 (20.3%), Ex19 in 55 (27.2%), and Ex18 in 4 (2%). RESULTS: Patients with and without EGFR mutations had similar DFS (26.2% vs 24.6%, respectively; p = 0.280) and OS (64.9% vs 54.2%, respectively; p = 0.564). Patients with Ex19 tumors had significantly better DFS (38.8% vs 11.8%, p = 0.001) and tended to have better OS (78.3% vs 48.3%, p = 0.123) than those with Ex21 tumors. For pN1, patients with Ex19 tumors had a longer disease-free interval (54.0 vs 22.3 months, p = 0.003) and median survival time (81.0 vs 50.6 months, p = 0.022) than those with Ex21 tumors. For pN2, patients with Ex19 tumors had longer disease-free interval than those with Ex21 tumors (43.6 vs 30.1 months, p = 0.109). Multivariate analysis showed Ex21 was a prognosticator of poor DFS (hazard ratio, 2.25; 95% confidence interval, 1.21 to 4.20). CONCLUSIONS: For pN1-N2 pulmonary adenocarcinoma, Ex21 mutation was associated with poorer prognosis than Ex19 mutation. Thus, EGFR mutation status should be considered when predicting prognosis. PMID- 27553498 TI - Report of the 2015 Society of Thoracic Surgeons Congenital Heart Surgery Practice Survey. AB - BACKGROUND: The Society of Thoracic Surgeons Workforce on Congenital Heart Surgery (CHS) undertook a third subspecialty Practice Survey (2005, 2010, 2015) to obtain contemporary data. METHODS: A search for potential participants was conducted using multiple directories and websites. The survey instrument was widely distributed electronically. All surgeons listing congenital or pediatric cardiac surgery among interests were targeted. RESULTS: There were a total of 213 respondents: 177 (83%) were practicing congenital heart surgeons (median age 50 years; range, 34 to 80 years; 93% men), 9 (4%) were CHS trainees, 17 (8%) were retired congenital heart surgeons, and 10 (5%) were others. For practicing surgeons, mean duration of postgraduate training was 10 +/- 2 years and 151 (85%) were CHS-board certified. Median practice duration for congenital heart surgeons was 15 years (less than 1 to 42 years). Work hours per week were greater than 70 for 74 (42%) surgeons, 103 (58%) work at a freestanding children's hospital, and 113 (64%) have full academic appointments. Caseload for 47 (27%) surgeons was less than 100 cases/year and 42 (24%) performed greater than 200 cases/year. For practicing surgeons, anticipated median retirement age was 66 years (range, 55 to 83 years), 31 (18%) estimated <=5 years to retirement, and 163 (92%) were extremely or very satisfied in their career. CONCLUSIONS: These data provide contemporary insights regarding the CHS workforce in North America and should help facilitate rational plans to address the needs of an expanding patient population. PMID- 27553499 TI - Glasgow Prognostic Score Class 2 Predicts Prolonged Intensive Care Unit Stay in Patients Undergoing Pneumonectomy. AB - BACKGROUND: The Glasgow prognostic score (GPS) is an inflammation-based score based on albuminemia and C-reactive protein concentration proved to be associated with cancer-specific survival in several neoplasms. The present study explored the immediate postoperative value of the GPS for patients undergoing pneumonectomy for lung cancer. METHODS: The value of the GPS preoperatively was studied in 250 patients undergoing pneumonectomy for non-small cell lung cancer (NSCLC). We analyzed overall postoperative complications, pulmonary and cardiac complications, 30-day postoperative death, reoperation for early complications, intensive care unit (ICU) length of stay and total length of hospital stay. RESULTS: Patients with a GPS of 0 and 1 had a mean ICU length of stay of 0.8 days, whereas patients with a GPS of 2 had a mean ICU stay of 5.0 days (p = 0.004). The postoperative mortality rate in patients with a GPS of 2 was much higher than in patients with a GPS of 1 and 2, although it was not statistically significant (p = 0.083). CONCLUSIONS: A preoperative GPS of 2 effectively predicts a prolonged ICU stay in patients who undergo pneumonectomy for cancer. The score may be proposed as an easy-to-determine, economical, and fast preoperative tool to plan and optimize ICU admissions after elective pneumonectomy. PMID- 27553500 TI - Risk Factors for Sternal Complications After Cardiac Operations: A Systematic Review. AB - Early detection of patients at risk of sternal complications is essential to facilitate prevention and optimize timely intervention. A systematic review and meta-analysis was conducted to identify risk factors associated with sternal complications. The review included 17 full-text studies, of which 10 were entered into meta-analyses. Female gender, diabetes mellitus, obesity, bilateral internal mammary artery grafts, reoperation for postoperative complications, and blood product requirement were reported as significant predictors of sternal infection. The compilation of these risk factors may help to screen and stratify patients at risk of impaired sternal healing and warrants further investigation. PMID- 27553501 TI - Variation in Red Blood Cell Transfusion Practices During Cardiac Operations Among Centers in Maryland: Results From a State Quality-Improvement Collaborative. AB - BACKGROUND: Variation in red blood cell (RBC) transfusion practices exists at cardiac surgery centers across the nation. We tested the hypothesis that significant variation in RBC transfusion practices between centers in our state's cardiac surgery quality collaborative remains even after risk adjustment. METHODS: Using a multiinstitutional statewide database created by the Maryland Cardiac Surgery Quality Initiative (MCSQI), we included patient-level data from 8,141 patients undergoing isolated coronary artery bypass (CAB) or aortic valve replacement at 1 of 10 centers. Risk-adjusted multivariable logistic regression models were constructed to predict the need for any intraoperative RBC transfusion, as well as for any postoperative RBC transfusion, with anonymized center number included as a factor variable. RESULTS: Unadjusted intraoperative RBC transfusion probabilities at the 10 centers ranged from 13% to 60%; postoperative RBC transfusion probabilities ranged from 16% to 41%. After risk adjustment with demographic, comorbidity, and operative data, significant intercenter variability was documented (intraoperative probability range, 4% 59%; postoperative probability range, 13%-39%). When stratifying patients by preoperative hematocrit quartiles, significant variability in intraoperative transfusion probability was seen among all quartiles (lowest quartile: mean hematocrit value, 30.5% +/- 4.1%, probability range, 17%-89%; highest quartile: mean hematocrit value, 44.8% +/- 2.5%; probability range, 1%-35%). CONCLUSIONS: Significant variation in intercenter RBC transfusion practices exists for both intraoperative and postoperative transfusions, even after risk adjustment, among our state's centers. Variability in intraoperative RBC transfusion persisted across quartiles of preoperative hematocrit values. PMID- 27553502 TI - Elevated Hemoglobin A1c Is Associated With Lower Socioeconomic Position and Increased Postoperative Infections and Longer Hospital Stay After Cardiac Surgical Procedures. AB - BACKGROUND: Patients with elevated hemoglobin A1c (HbA1c) levels have an increased risk of adverse short- and long-term outcomes after cardiac surgical procedures. Whether elevated HbA1c levels are associated with lower socioeconomic position (SEP) has been unknown. METHODS: All adult patients undergoing cardiac surgical procedures at Kansas University Medical Center in Kansas City, Kansas in 2014 (n = 567) were reviewed. Of those patients, 531 had a preoperative HbA1c level measured. HbA1c was delineated as 7% or lower or greater than 7%. The two aims of this study were to evaluate a possible association of HbA1c and SEP and to evaluate for a possible association of HbA1c levels and poor outcomes after cardiac surgical procedures. The primary postsurgical outcomes were infections and intensive care unit length of stay. RESULTS: HbA1c levels greater than 7% were associated with lower SEP (p = 0.005) and with increased risk of infection postoperatively (p < 0.001). Total hospital length of stay tended to be longer for patients with HbA1c greater than 7% (p = 0.009). CONCLUSIONS: Elevated HbA1c levels are associated with lower SEP. This association not only may hinder the ability to correct HbA1c levels, but also may impart a risk for elevated HbA1c levels. Additionally, patients who present for cardiac operations with HbA1c greater than 7% have an increased risk of postoperative infections. PMID- 27553503 TI - Ascending Aorta and Hemiarch Replacement Combined With Modified Triple-Branched Stent Graft Implantation for Repair of Acute DeBakey Type I Aortic Dissection. AB - BACKGROUND: To simplify extensive repair of acute DeBakey type I aortic dissection, ascending aorta and hemiarch replacement combined with modified triple-branched stent graft implantation was developed. The descriptions and early results of this technique are reported. METHODS: From August 2014 to September 2015, 116 patients with acute DeBakey type I aortic dissection underwent ascending aorta and hemiarch replacement combined with modified triple branched stent graft implantation. Clinical data of all patients were retrospectively reviewed. Survivors were followed up prospectively by computed tomography angiography. RESULTS: The cardiopulmonary bypass time was 131.5 +/- 10.7 minutes, the aortic cross-clamp time was 50.0 +/- 9.9 minutes, and the selective cerebral perfusion and lower body arrest time was 17.2 +/- 2.2 minutes. The in-hospital mortality rate was 3.4%. Two patients were lost during follow-up. One patient died of a cerebrovascular accident 2 months after discharge, and another died of chronic renal failure 5 months after discharge. At the 3-month postoperative scans, complete thrombus formation of the false lumen around the implanted modified triple-branched stent graft occurred in all survivors, at the diaphragmatic level in 69.7% patients, and at the superior mesenteric arterial level in 8.3% patients. CONCLUSIONS: Extensive thoracic aorta repair of acute type I aortic dissection can be performed simply by combining ascending aorta and hemiarch replacement with modified triple-branched stent graft implantation. This technique can reduce the risk and technical difficulty of extensive thoracic aorta repair to levels close to those seen with ascending aorta and hemiarch graft replacement with open distal anastomosis. PMID- 27553504 TI - Prevalence of maternal near miss and community-based risk factors in Central Uganda. AB - OBJECTIVE: To examine the prevalence of maternal near-miss (MNM) and its associated risk factors in a community setting in Central Uganda. METHODS: A cross-sectional research design employing multi-stage sampling collected data from women aged 15-49 years in Rakai, Uganda, who had been pregnant in the 3years preceding the survey, conducted between August 10 and December 31, 2013. Additionally, in-depth interviews were conducted. WHO-based disease and management criteria were used to identify MNM. Binary logistic regression was used to predict MNM risk factors. Content analysis was performed for qualitative data. RESULTS: Survey data were collected from 1557 women and 40 in-depth interviews were conducted. The MNM prevalence was 287.7 per 1000 pregnancies; the majority of MNMs resulted from hemorrhage. Unwanted pregnancies, a history of MNM, primipara, pregnancy danger signs, Banyakore ethnicity, and a partner who had completed primary education only were associated with increased odds of MNM (all P<0.05). CONCLUSIONS: MNM morbidity is a significant burden in Central Uganda. The present study demonstrated higher MNM rates compared with studies employing organ-failure MNM-diagnostic criteria. These findings illustrate the need to look beyond mortality statistics when assessing maternal health outcomes. Concerted efforts to increase supervised deliveries, access to emergency obstetric care, and access to contraceptives are warranted. PMID- 27553505 TI - Light and electron microscopic analyses of the high deformability of adhesive toe pads in White's tree frog, Litoria caerulea. AB - White's tree frog (Litoria caerulea) has large, adhesive toe pads that are among the softest of all known biological structures. To explore the morphological basis for the physical properties of the toe pads, the internal microstructure of the toe pads in L. caerulea was examined using both light and transmission electron microscopy. Three design elements that are distinct from other areas of skin were observed. First, the keratinocytes comprising the adhesive surface of the toe pad all contained keratin filament bundles (tonofibrils) exhibiting structural anisotropy. Specifically, the curved conformation of the hierarchical (branching) tonofibrils was characterized by the formation of anastomoses consisting of tonofibrils beneath the adhesive cell surface and stem keratin filament bundles concentrated in the lower-middle part of the dorsal-side of adhesive cells. Second, the cytoplasm of keratinocytes in the most superficial cell layer contained glycoproteins (stained by periodic acid/Schiff reagent) that are considered to confer high viscoelasticity. Third, the dermis contained large lymph spaces interspersed with elastic fibers and collagen fibers, which were relatively sparsely distributed compared to the dorsal skin of the toe pads. The profiles of these structures were easily deformed by the slight application of pressure. These findings reaffirmed that the unique internal architecture of the toe pads in L. caerulea contributed to their remarkable softness and high deformability, which in turn increased the contact area and provided improved adaptability to the local topography of natural surfaces. J. Morphol. 277:1509 1516, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27553506 TI - Separation of ballistic and diffusive fluorescence photons in confocal Light Sheet Microscopy of Arabidopsis roots. AB - Image quality in light-sheet fluorescence microscopy is strongly affected by the shape of the illuminating laser beam inside embryos, plants or tissue. While the phase of Gaussian or Bessel beams propagating through thousands of cells can be partly controlled holographically, the propagation of fluorescence light to the detector is difficult to control. With each scatter process a fluorescence photon loses information necessary for the image generation. Using Arabidopsis root tips we demonstrate that ballistic and diffusive fluorescence photons can be separated by analyzing the image spectra in each plane without a priori knowledge. We introduce a theoretical model allowing to extract typical scattering parameters of the biological material. This allows to attenuate image contributions from diffusive photons and to amplify the relevant image contributions from ballistic photons through a depth dependent deconvolution. In consequence, image contrast and resolution are significantly increased and scattering artefacts are minimized especially for Bessel beams with confocal line detection. PMID- 27553507 TI - Editorial overview: Host pathogens: the interplay between host innate and adaptive immune systems and pathogens. PMID- 27553508 TI - Proteomic definitions of basement membrane composition in health and disease. AB - Basement membranes are formed from condensed networks of extracellular matrix (ECM) proteins. These structures underlie all epithelial, mesothelial and endothelial sheets and provide an essential structural scaffold. Candidate-based investigations have established that predominant components of basement membranes are laminins, collagen type IV, nidogens and heparan sulphate proteoglycans. More recently, global proteomic approaches have been applied to investigate ECM and these analyses confirm tissue-specific ECM proteomes with a high degree of complexity. The proteomes consist of structural as well as regulatory ECM proteins such as proteases and growth factors. This review is focused on the proteomic analysis of basement membranes and illustrates how this approach can be used to build our understanding of ECM regulation in health and disease. PMID- 27553510 TI - Transport and transcriptional regulation of oil production in plants. AB - Triacylglycerol (TAG) serves as an energy reservoir and phospholipids as build blocks of biomembrane to support plant life. They also provide human with foods and nutrients. Multi-compartmentalized biosynthesis, trafficking or cross membrane transport of lipid intermediates or precursors and their regulatory mechanisms are not fully understood. Recent progress has aided our understanding of how fatty acids (FAs) and phospholipids are transported between the chloroplast, the cytoplasm, and the endoplasmic reticulum (ER), and how the ins and outs of lipids take place in the peroxisome and other organelles for lipid metabolism and function. In addition, information regarding the transcriptional regulation network associated with FA and TAG biosynthesis has been further enriched. Recent breakthroughs made in lipid transport and transcriptional regulation has provided significant insights into our comprehensive understanding of plant lipid biology. This review attempts to highlight the recent progress made on lipid synthesis, transport, degradation, and their regulatory mechanisms. Metabolic engineering, based on these knowledge-powered technologies for production of edible oils or biofuels, is reviewed. The biotechnological application of metabolic enzymes, transcription factors and transporters, for oil production and composition improvement, are discussed in a broad context in order to provide a fresh scenario for researchers and to guide future research and applications. PMID- 27553511 TI - Medium-term prognosis of an incident cohort of parkinsonian patients compared to controls. AB - BACKGROUND: The best data on prognosis comes from population-based incident cohorts but few such cohorts exist for Parkinson's disease and atypical parkinsonism. METHODS: The PINE study is a prospective follow-up study of an incident cohort of people with degenerative or vascular parkinsonism and age-sex matched controls. Participants have annual follow-up from diagnosis until death with review of primary/secondary care records and linkage to the UK death register. Data are collected on survival, disability (dependency on others for activities of daily living) and institutionalization. Research criteria are used to guide the clinical diagnosis, which is updated annually. We compared all-cause mortality, disability and institutionalization in patients (subdivided by diagnosis) and controls, adjusted for important confounders. RESULTS: 323 incident parkinsonian patients (199 Parkinson's disease, 124 atypical parkinsonism, mean age at diagnosis 75yrs) and 262 controls (mean age 75yrs) had 1349 and 1334 person-years follow-up respectively (maximum follow-up 10 years). All outcomes were worse in parkinsonian patients than controls, especially in atypical parkinsonism (adjusted mortality hazards ratios Parkinson's disease 2.49, 95%CI 1.72-3.58, atypical parkinsonism, 6.85, 95%CI 4.78-9.81). Median survival times for Parkinson's disease and atypical parkinsonism were 7.8 and 2.7 years respectively but were very age-dependent. At three years the rates of death or dependency were controls 21%, Parkinson's disease 46%, atypical parkinsonism 96% whilst overall institutionalization rates were 5%, 15% and 55% respectively. CONCLUSION: The prognosis of Parkinson's disease and atypical parkinsonism in this unselected incident cohort was significantly worse than previously reported. This has important implications for patient management. PMID- 27553509 TI - Fibrin mechanical properties and their structural origins. AB - Fibrin is a protein polymer that is essential for hemostasis and thrombosis, wound healing, and several other biological functions and pathological conditions that involve extracellular matrix. In addition to molecular and cellular interactions, fibrin mechanics has been recently shown to underlie clot behavior in the highly dynamic intra- and extravascular environments. Fibrin has both elastic and viscous properties. Perhaps the most remarkable rheological feature of the fibrin network is an extremely high elasticity and stability despite very low protein content. Another important mechanical property that is common to many filamentous protein polymers but not other polymers is stiffening occurring in response to shear, tension, or compression. New data has begun to provide a structural basis for the unique mechanical behavior of fibrin that originates from its complex multi-scale hierarchical structure. The mechanical behavior of the whole fibrin gel is governed largely by the properties of single fibers and their ensembles, including changes in fiber orientation, stretching, bending, and buckling. The properties of individual fibrin fibers are determined by the number and packing arrangements of double-stranded half-staggered protofibrils, which still remain poorly understood. It has also been proposed that forced unfolding of sub-molecular structures, including elongation of flexible and relatively unstructured portions of fibrin molecules, can contribute to fibrin deformations. In spite of a great increase in our knowledge of the structural mechanics of fibrin, much about the mechanisms of fibrin's biological functions remains unknown. Fibrin deformability is not only an essential part of the biomechanics of hemostasis and thrombosis, but also a rapidly developing field of bioengineering that uses fibrin as a versatile biomaterial with exceptional and tunable biochemical and mechanical properties. PMID- 27553512 TI - Determinants of disability in cervical dystonia. AB - BACKGROUND: Cervical dystonia (CD) is characterized by involuntary muscle contractions causing abnormal postures and/or twisting movements of the head and neck. These motor symptoms can have a major impact on disability. Treatment with botulinum toxin injections aims to reduce motor symptoms, and therefore disability. Despite motor improvements, many patients still experience difficulties with performing daily life activities. To optimize treatment, other factors that determine disability should be identified. OBJECTIVE: To explore and identify clinical characteristics that relate to disability in CD. METHODS: Data on disability, severity of dystonia, anxiety, depression, pain and quality of life of 96 CD patients was analyzed with a principal component analysis (PCA). Multiple regression analysis was performed to determine which components derived from the PCA explain most of the variance in disability. RESULTS: PCA revealed five components (disability, psychiatric features, pain, physical function and severity of dystonia), explaining 74.4% of the variance in disability. Multivariate association between disability and the other components was statistically significant (R2 change 0.433, F change (4-86) = 22.39, p = .000). Psychiatric features had the largest contribution to disability (standardized beta = 0.555, p = 0.000) followed by pain (standardized beta = 0.232 p = 0.004). Physical functioning (standardized beta = 0.059 p = 0.507) and severity of dystonia (standardized beta = -0.001 p = 0.991) had no significant contribution. CONCLUSIONS: In CD patients, psychiatric features and pain are important determinants of disability. Interventions to reduce psychiatric problems and pain should have a more prominent role in the treatment of CD patients in order to improve disability levels. PMID- 27553513 TI - Cerebral peduncle angle: Unreliable in differentiating progressive supranuclear palsy from other neurodegenerative diseases. AB - INTRODUCTION: The significant symptom overlap between progressive supranuclear palsy (PSP) and other parkinsonian neurodegenerative diseases frequently results in misdiagnosis. However, neuroimaging can be used to quantify disease-related morphological changes and specific markers. The cerebral peduncle angle (CPA) has been shown to differentiate clinically diagnosed PSP from other parkinsonian diseases but this result has yet to be confirmed in autopsy-proven disease. METHODS: Magnetic resonance imaging (MRI) scans were obtained for 168 patients representing 69 medical facilities. Following randomization, the images were divided into two groups (Type 1 and Type 2) based upon midbrain morphological differences. Two readers were blinded and independently measured the CPA of 146 patients with autopsy-proven progressive supranuclear palsy (PSP; n = 54), corticobasal degeneration (n = 16), multiple system atrophy (MSA; n = 11) and Lewy body disease (n = 65). RESULTS: Applying two separate measurement techniques revealed no statistically significant differences in CPA measurements among any study groups regardless of classification measurement approach. The interobserver agreement showed significant differences in measurements using the Type 2 approach. CONCLUSION: Measuring the CPA on MRI is not a reliable way of differentiating among patients with PSP, corticobasal degeneration, MSA, or Lewy body disease. PMID- 27553514 TI - Acquired Resistance to First-Line Afatinib and the Challenges of Prearranged Progression Biopsies. AB - OBJECTIVES: The mechanisms of acquired resistance to the irreversible EGFR inhibitor afatinib are not well documented. We performed this prospective clinical trial to determine the prevalence of the mutation T790M in afatinib resistant patients. METHODS: Eligible patients had EGFR mutations; they were tyrosine kinase inhibitor-naive and were treated with afatinib, 40 mg daily. At enrollment, patients consented to a future repeat biopsy at the time of acquired resistance. RESULTS: A total of 24 patients were enrolled. The objective response rate was 58% (95% confidence interval [CI]: 37-78) with a median progression-free survival of 11.4 months (95% CI: 5.9-13.7) and median overall survival of 20.8 months (95% CI: 15.1-40.5). Of the 24 patients enrolled, 23 progressed and only 14 completed repeat biopsy at time of progression, with 11 samples sufficient for molecular analysis. Of those 11 patients, four (36% [95% CI: 10.9-69.2]) harbored T790M. CONCLUSIONS: T790M is likely a common resistance mechanism in patients treated with first-line afatinib. Although repeat biopsies at progression are crucial in elucidating resistance mechanisms, this study suggests that clinical and technical issues often limit their feasibility, highlighting the importance of developing noninvasive tumor-genotyping strategies. PMID- 27553515 TI - Lobe-Specific Lymph Node Dissection as a Standard Procedure in Surgery for Non Small Cell Lung Cancer: A Propensity Score Matching Study. AB - INTRODUCTION: Systematic lymph node dissection (SND) is the standard procedure in surgical treatment for NSCLC, but the value of this approach for survival and nodal staging is still uncertain. In this study, we evaluated the potential of lobe-specific lymph node dissection (L-SND) in surgery for NSCLC by using a propensity score matching method. METHODS: From 2005 to 2007, 565 patients with cT1a-2b N0-1 M0 NSCLC underwent lobectomy with lymph node dissection at our 10 affiliated hospitals. Patients were classified into groups that underwent nodal sampling, L-SND, and systematic dissection SND on the basis of pathological data for the number and extent of nodal resection. A total of 77 patients with insufficient pathological data were excluded from the study. RESULTS: Overall, survival did not differ significantly among the groups (p = 0.552), but the rate of detection of pN2 in the SND group (13.1%) was significantly higher than in the nodal sampling (3.3%) and L-SND (9.0%) groups (p = 0.010). However, given the many confounding factors in the patient characteristics in each group, outcomes were reevaluated using a propensity score matching method for the L-SND and SND groups. After matching, the two groups had no significant differences in 5-year overall survival (73.5% for L-SND versus 75.3% for SND, p = 0.977) and pN2 detection (8.2% in both groups, p = 0.779). CONCLUSIONS: These results suggest that lobe-specific lymph node dissection has the potential to be a standard procedure in surgical treatment for NSCLC. PMID- 27553516 TI - Designing Quantum Spin-Orbital Liquids in Artificial Mott Insulators. AB - Quantum spin-orbital liquids are elusive strongly correlated states of matter that emerge from quantum frustration between spin and orbital degrees of freedom. A promising route towards the observation of those states is the creation of artificial Mott insulators where antiferromagnetic correlations between spins and orbitals can be designed. We show that Coulomb impurity lattices on the surface of gapped honeycomb substrates, such as graphene on SiC, can be used to simulate SU(4) symmetric spin-orbital lattice models. We exploit the property that massive Dirac fermions form mid-gap bound states with spin and valley degeneracies in the vicinity of a Coulomb impurity. Due to electronic repulsion, the antiferromagnetic correlations of the impurity lattice are driven by a super exchange interaction with SU(4) symmetry, which emerges from the bound states degeneracy at quarter filling. We propose that quantum spin-orbital liquids can be engineered in artificially designed solid-state systems at vastly higher temperatures than achievable in optical lattices with cold atoms. We discuss the experimental setup and possible scenarios for candidate quantum spin-liquids in Coulomb impurity lattices of various geometries. PMID- 27553517 TI - Non-destructive prediction of pigment content in lettuce based on visible-NIR spectroscopy. AB - BACKGROUND: Lettuce (Lactuca sativa L.) is one of the most important salad vegetables in the world, with a number of head shapes, leaf types and colors. The lettuce pigments play important physiological functions, such as photosynthetic processes and light stress defense, but they also benefit human health because of their antioxidant action and anticarcinogenic properties. In this study three lettuce cultivars were grown under different farming systems, and partial least squares models were built to predict the leaf chlorophyll, carotenoid and anthocyanin content. RESULTS: The three proposed models resulted in high coefficients of determination and variable importance for the projection values, as well as low estimative errors for calibration and external validation datasets. These results confirmed that it is possible to accurately predict chlorophyll, carotenoid and anthocyanin content of green and red lettuces, grown in different farming systems, based on the spectral reflectance from 500 to 1000 nm. CONCLUSION: The proposed models were adequate for estimating lettuce pigments in a quick and non-destructive way, representing an alternative to conventional measurement methods. Prediction accuracies were improved by using the detrending, smoothing and first derivative pretreatments to the original spectral signatures prior to estimating lettuce chlorophyll, carotenoid and anthocyanin content, respectively. (c) 2016 Society of Chemical Industry. PMID- 27553518 TI - Low voltage-driven oxide phototransistors with fast recovery, high signal-to noise ratio, and high responsivity fabricated via a simple defect-generating process. AB - We have demonstrated that photo-thin film transistors (photo-TFTs) fabricated via a simple defect-generating process could achieve fast recovery, a high signal to noise (S/N) ratio, and high sensitivity. The photo-TFTs are inverted-staggered bottom-gate type indium-gallium-zinc-oxide (IGZO) TFTs fabricated using atomic layer deposition (ALD)-derived Al2O3 gate insulators. The surfaces of the Al2O3 gate insulators are damaged by ion bombardment during the deposition of the IGZO channel layers by sputtering and the damage results in the hysteresis behavior of the photo-TFTs. The hysteresis loops broaden as the deposition power density increases. This implies that we can easily control the amount of the interface trap sites and/or trap sites in the gate insulator near the interface. The photo TFTs with large hysteresis-related defects have high S/N ratio and fast recovery in spite of the low operation voltages including a drain voltage of 1 V, positive gate bias pulse voltage of 3 V, and gate voltage pulse width of 3 V (0 to 3 V). In addition, through the hysteresis-related defect-generating process, we have achieved a high responsivity since the bulk defects that can be photo-excited and eject electrons also increase with increasing deposition power density. PMID- 27553519 TI - Erratum. PMID- 27553520 TI - Analysis of large-scale whole exome sequencing data to determine the prevalence of genetically-distinct forms of neuronal ceroid lipofuscinosis. AB - The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, mostly recessive neurodegenerative lysosomal storage diseases. While clinically similar, they are genetically distinct and result from mutations in at least twelve different genes. Estimates of NCL incidence range from 0.6 to 14 per 100,000 live births but vary widely between populations and are influenced by whether patients are classified based upon clinical or genetic criteria. We investigated mutations in twelve NCL genes in ~61,000 individuals represented in the Exome Aggregation Consortium (ExAC) whole exome sequencing database. Variants were extracted from ExAC and pathogenic alleles were differentiated from neutral polymorphisms using annotated variant databases and missense mutation prediction tools. Carrier frequency was dependent on ethnicity, with the highest (1/75) observed for PPT1 in the Finnish. When data are adjusted for ethnic diversity within the USA, PPT1, TPP1 and CLN3 carrier frequencies were found to be the highest of the NCLs, each at ~1/500. Carrier frequencies calculated from ExAC correlated well with incidence estimated from numbers of living NCL patients in the US. In addition, the analysis identified numerous variants that are annotated as pathogenic in public repositories but have a predicted frequency that is not consistent with patient studies. These variants appear to be neutral polymorphisms that are reported as pathogenic without validation. Based upon literature reports, such alleles may be annotated in public databases as pathogenic and this propagates errors that can have clinical consequences. PMID- 27553521 TI - Physiological responses and tolerance of kenaf (Hibiscus cannabinus L.) exposed to chromium. AB - Selection of kenaf species with chromium (Cr) tolerance and exploring the physiological mechanisms involved in Cr tolerance are crucial for application of these species to phyto-remediation. In the present study, a hydroponic experiment was conducted to investigate the variation in two kenaf cultivars, K39-2 and Zhe50-3 under Cr stress. At the same Cr concentration, the tolerance index (TI) of K39-2 was higher than that of Zhe50-3, indicating that K39-2 may be more tolerant to Cr than Zhe50-3. It was also observed that high concentration of chromium was accumulated both in the shoots and the roots of Hibiscus cannabinus L. The leaves of K39-2 accumulated 4760.28mgkg(-1) of dry weight under 1.50mM Cr stress, and the roots accumulated 11,958.33mgkg(-1). Physiological response shows that the antioxidant enzymes' superoxide dismutase (SOD), catalase activity (CAT) and peroxidase (POD) activities increased in the leaves and decreased in roots of the Cr-stressed plants nearly compared to the control. Moreover, the variation of antioxidant enzymes activities indicated Zhe50-3 was more vulnerable than K39-2, and the contents of the non-protein thiol pool (GSH, NPT and PCs) were higher in K39-2 than Zhe50-3 with the increased Cr concentration. Based on the observations above, it can be concluded that the well-coordinated physiological changes confer a greater Cr tolerance to K39-2 than Zhe50-3 under Cr exposure, and Hibiscus cannabinus L. has a great accumulation capacity for chromium. PMID- 27553522 TI - Transcultural adaptation, validation and assessment of the psychometric properties of the spanish version of the Western Ontario Shoulder Instability Index questionnaire. AB - OBJECTIVE: The aim of the present study is to present a transcultural adaptation and validation of the Western Ontario Shoulder Instability Index questionnaire into Spanish (Spain), and to assess its psychometric properties. MATERIAL AND METHODS: The transcultural adaptation was conducted according to sequential forward and backward translation approach. A pilot study was subsequently performed to ensure acceptable psychometric properties. The Western Ontario Shoulder Instability Index questionnaire was administered to 79 patients twice within a period of 2 months, and patients were stratified into 3 groups (cohorts). RESULTS: CONCLUSIONS: The Spanish version of the Western Ontario Shoulder Instability Index questionnaire is a valid, reliable tool, and highly sensitive to change to assess patients with shoulder instability. PMID- 27553523 TI - Serotonin transporter binding is reduced in seasonal affective disorder following light therapy. AB - OBJECTIVE: To investigate the effects of light therapy on serotonin transporter binding (5-HTT BPND ), an index of 5-HTT levels, in the anterior cingulate and prefrontal cortices (ACC and PFC) during winter in seasonal affective disorder (SAD). 5-HTT BPND fluctuates seasonally to a greater extent in SAD relative to health. We hypothesized that in SAD, 5-HTT BPND would be reduced in the ACC and PFC following light therapy. METHODS: Eleven SAD participants underwent [11 C] DASB positron emission tomography (PET) scans to measure 5-HTT BPND before and after 2 weeks of daily morning light therapy. RESULTS: The primary finding was a main effect of treatment on 5-HTT BPND in the ACC and PFC (repeated-measures manova, F(2,9) = 6.82, P = 0.016). This effect was significant in the ACC (F(1,10) = 15.11 and P = 0.003, magnitude of decrease, 11.94%) and PFC (F(1,10) = 8.33, P = 0.016, magnitude of decrease, 9.13%). 5-HTT BPND also decreased in other regions assayed following light therapy (repeated-measures manova, F(4,7) = 8.54, P = 0.028) including the hippocampus, ventral striatum, dorsal putamen, thalamus and midbrain (F(1,10) = 8.02-36.94, P < 0.0001-0.018; magnitude -8.83% to -16.74%). CONCLUSIONS: These results demonstrate that light therapy reaches an important therapeutic target in the treatment of SAD and provide a basis for improvement of this treatment via application of [11 C]DASB PET. PMID- 27553524 TI - Rasch modelling to deal with changes in the questionnaires used during long-term follow-up of cohort studies: a simulation study. AB - BACKGROUND: A specific measurement issue often occurs in cohort studies with long term follow-up: the substitution of the classic instruments used to assess one or several factors or outcomes studied by new, more reliable, more accurate or more convenient instruments. This study aimed to compare three techniques to deal with this issue when the substituted instrument is a questionnaire measuring a subjective phenomenon: one using only the items shared by the different questionnaires over time, i.e. computation of the raw score; the two others using every item, i.e. computation of the standardised score or estimation of the latent variable score using the Rasch model. METHODS: Two hundred databases were simulated, corresponding to longitudinal 10-item questionnaire data from three trajectory groups of subjects for the subjective phenomenon of interest ("increasing", "stable-low" or "stable-high" mean trajectory over time). Three copies of these databases were generated and the subjects' responses to some items were removed at some collection times leading to a number of shared items over time varying from 4 to 10 in the 800 datasets. The performances of Latent Class Growth Analysis (LCGA) applied to the raw score, the standardised score or the latent variable score were studied on these databases according to the number of shared items over time. RESULTS: Surprisingly, LCGA applied to the latent variable score estimate did not perform as well as LCGA applied to the standardised score, where it was the most efficient whatever the number of shared items. However, the proportions of correctly classified subjects by LCGA applied to the latent variable score were more balanced across trajectory groups. CONCLUSIONS: The use of the standardised score to deal with questionnaire changes over time was more efficient than the raw score and also, surprisingly, than the latent variable score. LCGA applied to the raw score was the least efficient and exhibited the most unbalanced misclassifications across trajectory groups. As prospective longitudinal studies with long-term follow-up are more and more common, researchers should be aware of this phenomenon and should reconsider the use of the raw score when changes in the questionnaires used occurred during follow-up. PMID- 27553525 TI - Electrolysis of a molten semiconductor. AB - Metals cannot be extracted by electrolysis of transition-metal sulfides because as liquids they are semiconductors, which exhibit high levels of electronic conduction and metal dissolution. Herein by introduction of a distinct secondary electrolyte, we reveal a high-throughput electro-desulfurization process that directly converts semiconducting molten stibnite (Sb2S3) into pure (99.9%) liquid antimony and sulfur vapour. At the bottom of the cell liquid antimony pools beneath cathodically polarized molten stibnite. At the top of the cell sulfur issues from a carbon anode immersed in an immiscible secondary molten salt electrolyte disposed above molten stibnite, thereby blocking electronic shorting across the cell. As opposed to conventional extraction practices, direct sulfide electrolysis completely avoids generation of problematic fugitive emissions (CO2, CO and SO2), significantly reduces energy consumption, increases productivity in a single-step process (lower capital and operating costs) and is broadly applicable to a host of electronically conductive transition-metal chalcogenides. PMID- 27553526 TI - Euroguidelines in Central and Eastern Europe (ECEE) conference and the Warsaw Declaration - a comprehensive meeting report. AB - OBJECTIVES: The objective of this paper is to summarize the outcomes of the Euroguidelines in Central and Eastern Europe (ECEE) conference held in Warsaw in February 2016. The main aim of this conference was to facilitate a discussion on European AIDS Clinical Society (EACS) guidelines implementation across the region and neighbouring countries and to present the current obstacles in benchmarking HIV care in Europe. METHODS: During a 2-day meeting, there were country-based presentations using a predefined template so as to make the data comparable and focus the discussion. Areas covered were country epidemiology, surveillance, national strategy for treatment and prevention, standards of care, access to care and treatment availability. Each participant filled in a questionnaire investigating HIV guidelines usage per country. RESULTS: In total, 16 Central and Eastern Europe (CEE) and neighbouring countries were represented at the conference: Albania, Armenia, Belarus, Croatia, Czech Republic, Estonia, Georgia, Hungary, Lithuania, Moldova, Poland, Romania, Russia, Serbia, Slovakia and Turkey. EACS guidelines version 7.1 were used in 14 (87%) countries. In 11 (69%) countries, national guidelines were available, of which eight had been recently updated. Half of the countries declared that they use World Health Organization (WHO) and Department of Health and Human Services (DHHS) guidelines, over one third the European Centre for Disease Prevention and Control (ECDC) HIV testing guidelines and one in five the International Antiviral Society-USA (IAS-USA) Panel guidelines from 2012. CONCLUSIONS: Participants declared their will to promote the widespread use of EACS guidelines for HIV infection in the CEE region and neighbouring countries by signing the Warsaw Declaration. They also emphasized the need to increase publishing of data from national cohorts in that region. PMID- 27553528 TI - Light-Weight Silver Plating Foam and Carbon Nanotube Hybridized Epoxy Composite Foams with Exceptional Conductivity and Electromagnetic Shielding Property. AB - Herein, light-weight and exceptionally conductive epoxy composite foams were innovatively fabricated for electromagnetic interference (EMI) shielding applications using multiwalled carbon nanotubes (MWCNTs) and 3D silver-coated melamine foam (SF) as conductive frameworks. A novel and nontraditional polymer microsphere was used to reduce the material density. The preformed, highly porous, and electrically conductive SF provided channels for fast electron transport. The MWCNTs were used to offset the decrease in conductive pathways due to the crystal defects of the silver layer and the insulating epoxy resin. Consequently, an exceptional conductivity of 253.4 S m(-1), a remarkable EMI shielding effectiveness of above 68 dB at 0.05-18 GHz, and a thermal conductivity of 0.305 W mK(-1) were achieved in these novel foams employing only 2 wt % of MWCNTs and 3.7 wt % of silver due to the synergistic effects that originated in the MWCNT and SF. These parameters are substantially higher than that achieved for the foam containing 2 wt % MWCNTs. Also, the SF exhibited little weakening in the foamability of the epoxy blends and the compression properties of resulting foams. All the results indicated that this effort provided a novel, simple, low cost, and easily industrialized concept for fabricating light-weight, high strength epoxy composite foams for high-performance EMI shielding applications. PMID- 27553527 TI - Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats. AB - The aim of this study was to investigate the involvement of androgen, mainly testosterone, in the expression of renal senescence marker protein-30 (SMP30) in male rats. We found that the renal SMP30 expression was up-regulated by endogenous testosterone stimulation during puberty. Interestingly, androgen deficient orchidectomized (ORX) rats exhibited lower SMP30 mRNA and protein expression in the kidney, and that was restored by testosterone propionate (TP) replacement. Abrogation of androgen receptor (AR) activity by co-treatment with flutamide abolished testosterone-induced SMP30 expression in the kidney as well as in the NRK52E cells. However, SMP30 expression was unaltered in the liver of ORX rats. We also showed a positive correlation between renal SMP30 expression and plasma testosterone level during the aging process. TP-induced SMP30 expression in ovariectomized (OVX) rats was observed and was an evidence to explain the gender difference of SMP30 levels. Immunofluorescence assay showed that renal SMP30 was specifically expressed in the proximal tubular segments of the kidney. The urinary Ca(2+) level was increased in both ORX and male aging rats. Taken together, our results indicate a novel role of testosterone in regulating SMP30 expression specifically in the kidney to contribute to urinary calcium absorption. PMID- 27553529 TI - Self-Assembled 1D-Nanowire Lasers of Perylenediimides. AB - The 1D nanostructures of perylenediimides (PDIs) have been readily obtained owing to strong cofacial pi-pi stacking interactions, which, however, subsequently render PDIs weakly emissive in the solid state. Therefore, organic solid-state lasers based on 1D nanostructures of PDIs have not been achieved yet. Herein, we prepared 1D-nanowires of N,N'-bis(1-ethylpropyl)-2,5,8,11-tetrakis(o methylphenyl)-perylene-3,4:9,10-tetracarboxylic acid diimide (mp-PDI), which stack into a loosely J-type arrangement. J-aggregation leads to a solid-state photoluminescence (PL) efficiency phi>18 % and the nanowires of mp-PDI exhibit excellent Fabry-Perot (FP) mode laser action. PMID- 27553530 TI - Histopathological changes of fibrosis in human extra-ocular muscle caused by botulinum toxin A. AB - We report the histopathological findings in 3 patients where injections of botulinum toxin were used prior to strabismus surgery. In all cases we found evidence of permanent extraocular muscle atrophy and fibrosis. PMID- 27553532 TI - [Mediastinum]. PMID- 27553531 TI - Beyond the N1: A review of late somatosensory evoked responses in human infants. AB - Somatosensory evoked potentials (SEPs) have been used for decades to study the development of somatosensory processing in human infants. Research on infant SEPs has focused on the initial cortical component (N1) and its clinical utility for predicting neurological outcome in at-risk infants. However, recent studies suggest that examining the later components in the infant somatosensory evoked response will greatly advance our understanding of somatosensory processing in infancy. The purpose of this review is to synthesize the existing electroencephalography (EEG) and magnetoencephalography (MEG) studies on late somatosensory evoked responses in infants. We describe the late responses that have been reported and discuss the utility of such responses for illuminating key aspects of somatosensory processing in typical and atypical development. PMID- 27553574 TI - A2 noradrenergic neurons regulate forced swim test immobility. AB - The Wistar-Kyoto (WKY) rat is a widely used animal model of depression, which is characterized by dysregulation of noradrenergic signaling. We previously demonstrated that WKY rats show a unique behavioral profile on the forced swim test (FST), characterized by high levels of immobility upon initial exposure and a greater learning-like response by further increasing immobility upon re exposure than the genetically related Wistar rats. In the current study we aimed to determine whether altered activation of brainstem noradrenergic cell groups contributes to this behavioral profile. We exposed WKY and Wistar rats, to either 5min of forced swim or to the standard two-day FST (i.e. 15min forced swim on Day 1, followed by 5min on Day 2). We then stained their brains for FOS/tyrosine hydroxylase double-immunocytochemistry to determine potential differences in the activation of the brainstem noradrenergic cell groups. We detected a relative hyperactivation in the locus coeruleus of WKY rats when compared to Wistars in response to both one- and two-day forced swim. In contrast, within the A2 noradrenergic cell group, WKY rats exhibited diminished levels of FOS across both days of the FST, suggesting their lesser activation. We followed up these observations by selectively lesioning the A2 neurons, using anti-dopamine-beta hydroxylase-conjugated saporin, in Wistar rats, which resulted in increased FST immobility on both days of the test. Together these data indicate that the A2 noradrenergic cell group regulates FST behavior, and that its hypoactivation may contribute to the unique behavioral phenotype of WKY rats. PMID- 27553575 TI - Effect of water- versus land-based exercise training as a component of a multidisciplinary intervention program for overweight and obese adolescents. AB - To compare water- versus land-based exercise programs, as part of a multidisciplinary intervention, on physical fitness and health-related quality of life in overweight and obese adolescents. A total of 151 overweight and obese adolescents (age: 13.2+/-1.8years) were divided into: 1) a water-based intervention (WB; n=28); 2) a land-based intervention (LB; n=57); and 3) a control group (CG; n=66). Anthropometric measures, body composition, flexibility, abdominal strength/endurance, cardiorespiratory fitness and health-related quality of life were assessed prior and by the end of a 16-week intervention. Both the water- and land-based interventions were part of a multidisciplinary program focusing on behavioral changes. Fat Mass (%) was significantly reduced in both intervention groups and a higher progression was observed in the WB group ( 9.8+/-7.2% versus -6.1+/-6.2%; p<0.05 for pre-to-post changes within-groups). However, LB increased more abdominal strength than WB (69.6+/-165.8% versus 53.4+/-83.4%; p<0.05) and significantly increased social (19.7+/-88.8%), psychosocial (5.1+/-15.1%) and total score (6.3+/-14.8%), which was observed in neither WB nor CG. The intervention groups did not change body weight (WB: -1.7+/ 5.3%; LB: 0.1+/-3.4%; p>0.05 for both groups) and increased (p<0.05) fat-free mass (WB: 4.6+/-4.0%; LB: 4.4+/-4.1%), VO2max (WB: 9.3+/-7.8%; LB: 11.0+/-13.4%), and physical dimension of quality of life (WB: 9.2+/-17.2%; LB: 8.9+/-18.0%) differently of what was observed in CG. The physical dimension improvement observed in the land-based and water-based samples was associated with decreased percentage fat mass (r=0.282 and 0.229; p<0.05). We suggest water- and land-based physical exercises within a multidisciplinary program promote similar improvements in body composition, physical fitness and health-related quality of life in overweight and obese adolescents. PMID- 27553577 TI - Oxidative Direct Arylation Polymerization Using Oxygen as the Sole Oxidant: Facile, Green Access to Bithiazole-Based Polymers. AB - The most appealing oxidant, molecular oxygen, is employed for the first time as the sole oxidant in the transition metal-catalyzed oxidative direct arylation polymerization (C-H/C-H-type DArP), which eliminates by-product formation of stoichiometric metal salts except for water . Compared to conventional approaches, other than the avoidance of an end-capping procedure, the current protocol is remarkably advanced in the aspect of eco-friendliness, step- and cost economy, and, of special significance, the purity of polymer products. As illustrative examples, six 5,5'-bithiazole-based polymers are synthesized using this new method, demonstrating higher number-average molecular weight (Mn up to 33 700) in better yields (up to 93 %) through only one step. The evolution of C H/C-H-type DArP from heavy metal salts to O2 alone as the oxidant could solve the problem of metal residues in polymers, which is considered harmful to the performance of devices. PMID- 27553578 TI - Vitamin D and cardiovascular disease in patients with systemic lupus erythematosus. PMID- 27553579 TI - Impact of metastasectomy on prognosis in patients treated with targeted therapy for metastatic renal cell carcinoma. AB - PURPOSE: We evaluated the value of metastasectomy in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC). METHODS: The medical records of 325 patients who presented with mRCC were reviewed; among these patients, 33 underwent complete metastasectomy followed by targeted therapy (complete metastasectomy group), 29 underwent incomplete metastasectomy followed by targeted therapy (incomplete metastasectomy group), and 263 treated with targeted therapy alone (non-metastasectomy group). We estimated progression-free and overall survivals using Kaplan-Meier curves. A Cox proportional hazards regression model was used to estimate the prognostic significance of metastasectomy. RESULTS: Clinicopathological variables did not differ among the three groups except for age, history of nephrectomy, type of metastasis, the International Metastatic Renal Cell Carcinoma Database Consortium risk groups, histology, and bone metastasis. The median progression-free survivals were 29.5, 18.8, and 14.8 months in the complete, incomplete, and non-metastasectomy groups (p < 0.001). Complete metastasectomy (hazard ratio 0.431, p = 0.001) was an independent predictor of disease progression, along with targeted agents, risk groups, sarcomatoid feature, and number of metastatic sites. The median overall survivals were 92.5, 29.6, and 23.5 months in the complete, incomplete, and non metastasectomy groups (p < 0.001). Complete metastasectomy (hazard ratio 0.378, p = 0.001) was an independent predictor of overall survival, along with targeted agents, type of metastasis, risk groups, sarcomatoid feature, and number of metastatic sites. CONCLUSIONS: Complete metastasectomy performed before targeted therapy might improve progression-free and overall survivals in patients with mRCC. PMID- 27553576 TI - Effect of anticonvulsive treatment on neuropsychological performance in children with BECTS. AB - INTRODUCTION: Benign epilepsy with centrotemporal spikes (BECTS) is a common epilepsy syndrome in childhood. Besides the occurrence of seizures, mild cognitive impairments and behavioral problems affecting language skills, spatial perception, memory, executive function, and academic achievement might be present. There is no international consensus about the decision whether or not to treat affected children. The influence of treatment on cognitive functions is debated. METHODS: Patients diagnosed with BECTS were assessed in short term auditory memory, long-term verbal memory, intelligence and behavior using the "number recall" test from the Kaufman assessment battery for children, the "verbal learning memory test", the "culture free intelligence test" and the "child behavior checklist" prior to a randomized controlled antiepileptic therapy and after a treatment period of 6 months with either sulthiame or levetiracetam. RESULTS: 43 of 44 randomized patients were analyzed. One patient had to be excluded due to protocol violation. Patients who completed the study showed a non significant improvement in parent-reported behavioral problems under therapy. Cognitive skills were not affected. CONCLUSION: The present data suggest that antiepileptic drug treatment of children with BECTS with either sulthiame or levetiracetam does not affect cognitive performance. Behavior improved in a subset of patients though not reaching statistical significance. PMID- 27553582 TI - Cosmetic surgery will be regulated more closely in England. PMID- 27553581 TI - Landiolol infusion during general anesthesia does not prevent postoperative atrial fibrillation in patients undergoing lung resection. AB - OBJECTIVE: We aimed to determine whether intraoperative low-dose infusion of landiolol, an ultra-short-acting beta blocker, can prevent postoperative atrial fibrillation (POAF) after lung resection. METHODS: A double-blind, randomized, controlled, preliminary study was performed in university academic hospital, single center. Fifty lung surgical patients were key-opened before enrollment of the originally planned 100 patients, who were randomized in a 1:1 ratio in each treatment arm. Landiolol was infused with a dosage of 5 MUg/kg/min during general anesthesia in the landiolol group, which was compared with the placebo control group with no landiolol. Atrial fibrillation (AF)-free survival curves were generated by means of Kaplan-Meier estimates and differences in survival were compared with the use of the log-rank test. We examined independent predictors of POAF by the multivariate logistic regression analysis using the perioperative parameters detected with the univariate analysis. RESULTS: The AF events were recorded for 7 days with Holter monitor in 5 of 25 patients in the landiolol group and 4 of 25 patients in the control group. Kaplan-Meier analysis showed that the landiolol group could not avoid the incidence of POAF in comparison with the placebo saline group (P = 0.806). The multivariate logistic regression analysis for prevalence of POAF identified only one statistically significant predictor: interleukin-6 (IL-6) sampled at 6 h after end of surgery. CONCLUSIONS: We failed to demonstrate that low-dose infusion of landiolol during general anesthesia could prevent the incidence of AF after lung resection. Only IL-6 sampled at 6 h after end of surgery significantly predicted POAF among pulmonary surgical patients. PMID- 27553583 TI - Visual signs and symptoms of corticobasal degeneration. AB - Corticobasal degeneration is a rare, progressive neurodegenerative disease and a member of the 'parkinsonian' group of disorders, which also includes Parkinson's disease, progressive supranuclear palsy, dementia with Lewy bodies and multiple system atrophy. The most common initial symptom is limb clumsiness, usually affecting one side of the body, with or without accompanying rigidity or tremor. Subsequently, the disease affects gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Corticobasal degeneration can be difficult to distinguish from other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid clinical diagnosis. Typical ocular features include increased latency of saccadic eye movements ipsilateral to the side exhibiting apraxia, impaired smooth pursuit movements and visuo-spatial dysfunction, especially involving spatial rather than object-based tasks. Less typical features include reduction in saccadic velocity, vertical gaze palsy, visual hallucinations, sleep disturbance and an impaired electroretinogram. Aspects of primary vision such as visual acuity and colour vision are usually unaffected. Management of the condition to deal with problems of walking, movement, daily tasks and speech problems is an important aspect of the disease. PMID- 27553585 TI - Liver cirrhosis and thyroid function: Friend or foe? AB - INTRODUCTION: The liver plays a central role in thyroid hormone metabolism, transport, and clearance. A normal function of both the thyroid gland and the liver is therefore necessary to maintain normal thyroid hormone levels and action. Data regarding thyroid function in patients with liver cirrhosis are scarce and variable. The most consistent finding is a decreased free triiodothyronine (fT3) level, which correlates with the severity of liver disease and has been proposed as a prognostic factor for liver-related complications. AIM OF THE STUDY: To evaluate thyroid hormone values in patients with stable liver cirrhosis and to compare them with healthy controls without liver disease. We also assessed the prevalence of thyroid autoimmunity and whether liver function tests correlated with thyroid function. MATERIAL AND METHODS: We performed a prospective case-control study in an endocrinological setting. Twenty-nine patients with stable cirrhosis (20 males and 9 females, mean age 60.97 +/- 7.17 years) were included in the case group and 50 healthy subjects (22 males and 28 females, mean age 61.70 +/- 13.00 years) in the control group. We excluded patients with confounding factors known to influence thyroid function. Levels of serum thyroid-stimulating hormone (TSH), fT3, free thyroxine (fT4) and anti-TPO antibodies (TPO-Ab) were measured. These thyroid hormone values were compared in both groups. Biochemical indices of liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], INR, total bilirubin, and albumin levels) were correlated with thyroid function tests. RESULTS: fT3 en fT4 levels were significantly lower in patients with cirrhosis than in healthy subjects (p = 0.001 and 0.002, respectively). TSH levels were not statistically significantly different in the two groups. The level of TPO-Ab was not increased in patients with cirrhosis compared to healthy controls. fT3 correlated negatively with the Child-Pugh score. DISCUSSION: These results indicate that, compared to healthy controls, patients with cirrhosis have decreased fT3 and fT4 levels and comparable TSH levels and may be consistent with findings of limited acquired central hypothyroidism as observed in the non-thyroidal illness syndrome (NTIS). fT3 levels correlated negatively with Child-Pugh score, a measure of severity of liver dysfunction. We did not find an increased prevalence of thyroid autoimmunity in these patients. PMID- 27553580 TI - Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan. AB - Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities. PMID- 27553584 TI - Resting and injury-induced inflamed periosteum contain multiple macrophage subsets that are located at sites of bone growth and regeneration. AB - Better understanding of bone growth and regeneration mechanisms within periosteal tissues will improve understanding of bone physiology and pathology. Macrophage contributions to bone biology and repair have been established but specific investigation of periosteal macrophages has not been undertaken. We used an immunohistochemistry approach to characterize macrophages in growing murine bone and within activated periosteum induced in a mouse model of bone injury. Osteal tissue macrophages (osteomacs) and resident macrophages were distributed throughout resting periosteum. In tissues collected from 4-week-old mice, osteomacs were observed intimately associated with sites of periosteal diaphyseal and metaphyseal bone dynamics associated with normal growth. This included F4/80+Mac-2-/low osteomac association with extended tracks of bone formation (modeling) on diphyseal periosteal surfaces. Although this recapitulated endosteal osteomac characteristics, there was subtle variance in the morphology and spatial organization of periosteal modeling-associated osteomacs, which likely reflects the greater structural complexity of periosteum. Osteomacs, resident macrophages and inflammatory macrophages (F4/80+Mac-2hi) were associated with the complex bone dynamics occurring within the periosteum at the metaphyseal corticalization zone. These three macrophage subsets were also present within activated native periosteum after bone injury across a 9-day time course that spanned the inflammatory through remodeling bone healing phases. This included osteomac association with foci of endochondral ossification within the activated native periosteum. These observations confirm that osteomacs are key components of both osteal tissues, in spite of salient differences between endosteal and periosteal structure and that multiple macrophage subsets are involved in periosteal bone dynamics. PMID- 27553586 TI - Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma. AB - Multicentric gliomas are very rare. Due to differences in their tumor types they remain enigmatic. We focused on the pathogenesis of multicentric gliomas and compared their immunoprofile with that of solitary gliomas. This retrospective study included 6 males and 8 females with multicentric glioma (8 glioblastomas, 2 anaplastic astrocytomas, 4 diffuse astrocytomas). Their age ranged from 27 to 75 years and all were treated between 2004 and June 2015. The expression of mutant isocitrate dehydrogenase 1 (IDH1), alpha-thalassemia X-linked intellectual disability (ATRX), p53, phosphatase and tensin homolog (PTEN), and epidermal growth factor receptor (EGFR) was examined immunohistochemically; for 1p19q analysis we used fluorescence in situ hybridization (FISH). In all patients, immunohistochemical staining was negative for mutant IDH1 and cytoplasmic PTEN; only 1 patient (7.1%) manifested nuclear PTEN positivity. FISH for 1p19q codeletion was negative in all 9 examined samples; 5 of 14 specimens (35.7%) were p53-positive, 9 (64.3%) were EGFR-positive, and 4 (28.6%) were ATRX-negative. The MIB-1 labeling index was 0.9-15.6% for grades II and III, and ranged between 17.3 and 52.4% for glioblastoma. Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. More studies are needed to confirm the molecular mechanisms underlying the pathogenesis of multicentric glioma. PMID- 27553587 TI - Unique quadruple immunofluorescence assay demonstrates mitochondrial respiratory chain dysfunction in osteoblasts of aged and PolgA(-/-) mice. AB - Fragility fractures caused by osteoporosis affect millions of people worldwide every year with significant levels of associated morbidity, mortality and costs to the healthcare economy. The pathogenesis of declining bone mineral density is poorly understood but it is inherently related to increasing age. Growing evidence in recent years, especially that provided by mouse models, suggest that accumulating somatic mitochondrial DNA mutations may cause the phenotypic changes associated with the ageing process including osteoporosis. Methods to study mitochondrial abnormalities in individual osteoblasts, osteoclasts and osteocytes are limited and impair our ability to assess the changes seen with age and in animal models of ageing. To enable the assessment of mitochondrial protein levels, we have developed a quadruple immunofluorescence method to accurately quantify the presence of mitochondrial respiratory chain components within individual bone cells. We have applied this technique to a well-established mouse model of ageing and osteoporosis and show respiratory chain deficiency. PMID- 27553588 TI - Initial stabilisation of preterm infants: a new resuscitation system with low imposed work of breathing for use with face mask or nasal prongs. AB - OBJECTIVE: T-piece resuscitation systems are pressure unstable and have high imposed work of breathing (iWOB). Pressure stable respiratory support with low iWOB might improve outcome. We have developed a new resuscitation system that can be used with nasal prongs or face mask. The aim of the study was to describe the in vitro performance of the new system and to perform a clinical feasibility trial of initial stabilisation of preterm infants. METHOD: A mechanical lung model was used to determine iWOB at increasing levels of continuous positive airway pressure (CPAP). The feasibility trial included 36 infants (27-34 weeks of gestation), who were randomised into three groups (T-piece, new system with face mask or new system with prongs). Collected data included problems with usage, safety, time to stable breathing, need for positive pressure ventilation and intubation. RESULTS: In the mechanical lung model, the new system reduced iWOB with 91.5% (mask) and 86.6% (medium prongs) compared with Neopuff (4 cm CPAP, p<0.001). Informed consent was obtained from 45 patients, 39 were randomised and 36 needed support. Randomisation resulted in an imbalance: The group of new system infants had lower gestational age compared with the T-piece group. Thirteen patients needed positive pressure ventilation (median 20 cm H2O). One infant was intubated. The study did not reveal problems with the equipment or safety. CONCLUSIONS: Compared with T-piece systems, the new system had a marked reduction in iWOB in bench tests. The feasibility trial did not reveal problems with usability or safety. PMID- 27553589 TI - MRI and spectroscopy in (near) term neonates with perinatal asphyxia and therapeutic hypothermia. AB - BACKGROUND: Previous studies have demonstrated the association of abnormalities on diffusion-weighted MRI (DW-MRI) and proton magnetic resonance spectroscopy (1H MRS) in infants with perinatal asphyxia. The use of therapeutic hypothermia might change this association. AIM: To study the association between DW-MRI and 1H-MRS and outcome after perinatal asphyxia and therapeutic hypothermia in infants with a gestational age of >=36 weeks. PATIENTS AND METHODS: Infants with perinatal asphyxia and therapeutic hypothermia (n=88) were included when an MR examination was performed within 7 days after birth. Apparent diffusion coefficient (ADC) values of the basal ganglia and thalamus were calculated, as were lactate/N acetylaspartate (LAC/NAA) and N-acetylaspartate/choline (NAA/Cho) ratios. Death or an abnormal neurodevelopment at >=24 months was considered an adverse outcome. Receiver operating characteristic analysis was performed to determine cut-off levels. RESULTS: Of the 88 infants, 22 died and 7 had an adverse neurodevelopmental outcome. In infants with an adverse outcome, ADC values of the basal ganglia and thalamus were significantly lower, and Lac/NAA ratios were significantly higher than in infants with a normal outcome. Areas under the curve of ADC of the basal ganglia, thalami and Lac/NAA ratio were 0.89, 0.88 and 0.87, respectively. NAA/Cho ratios were in this cohort not associated with outcome. CONCLUSIONS: During and after therapeutic hypothermia, low ADC values and high Lac/NAA ratios of the basal ganglia and thalamus are associated with an adverse outcome in infants with perinatal asphyxia. PMID- 27553590 TI - Neonatal hypoglycaemia: learning from claims. AB - OBJECTIVES: Neonatal hypoglycaemia is a potential cause of neonatal morbidity, and on rare but tragic occasions causes long-term neurodevelopmental harm with consequent emotional and practical costs for the family. The organisational cost to the NHS includes the cost of successful litigation claims. The purpose of the review was to identify themes that could alert clinicians to common pitfalls and thus improve patient safety. DESIGN: The NHS Litigation Authority (NHS LA) Claims Management System was reviewed to identify and review 30 claims for injury secondary to neonatal hypoglycaemia, which were notified to the NHS LA between 2002 and 2011. SETTING: NHS LA. PATIENTS: Anonymised documentation relating to 30 neonates for whom claims were made relating to neonatal hypoglycaemia. Dates of birth were between 1995 and 2010. INTERVENTIONS: Review of documentation held on the NHS LA database. MAIN OUTCOME MEASURES: Identifiable risk factors for hypoglycaemia, presenting clinical signs, possible deficits in care, financial costs of litigation. RESULTS: All claims related to babies of at least 36 weeks' gestation. The most common risk factor for hypoglycaemia was low birth weight or borderline low birth weight, and the most common reported presenting sign was abnormal feeding behaviour. A number of likely deficits in care were reported, all of which were avoidable. In this 10-year reporting period, there were 25 claims for which damages were paid, with a total financial cost of claims to the NHS of L162 166 677. CONCLUSIONS: Acknowledging that these are likely to be the most rare but most seriously affected cases, the clinical themes arising from these cases should be used for further development of training and guidance to reduce harm and redivert NHS funds from litigation to direct care. PMID- 27553591 TI - Implementation of the NICE prevention and treatment of early onset neonatal infection guideline: the Glasgow experience. PMID- 27553592 TI - Parameters indicative of persistence of valvular pathology at initial diagnosis in acute rheumatic carditis: the role of albumin and CD19 expression. AB - OBJECTIVE: The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). METHODS: Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. RESULTS: During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6+/-0.48g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. CONCLUSION: The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis. PMID- 27553593 TI - Suggested Protocol for Managing Acute Suppurative Cervical Lymphadenitis in Children to Reduce Unnecessary Surgical Interventions. AB - OBJECTIVES: The indications and benefits of surgery in the management of pediatric acute suppurative cervical lymphadenitis (ASCL) remain unclear. We aimed to design a management protocol focusing on the avoidance of unnecessary operation in pediatric ASCL patients. METHODS: The study population consisted of 45 pediatric patients with ASCL treated with antibiotics alone and 30 surgically treated patients. The primary outcome was the determination of differences in patient characteristics and radiologic findings in the 2 groups. The secondary outcome, after matching 20 cases with 20 controls, was to determine the benefits of surgery to patients. RESULTS: There were no significant differences between the 2 groups in patient characteristics and radiologic findings at initial presentation. In the matched case-control analysis, intravenous antibiotics alone yielded successful treatment outcomes when compared with surgery, with no significant differences in time to symptom resolution, normalized laboratory test results, and duration of hospitalization (all P > .05). CONCLUSIONS: The size and location of suppurated lymph nodes are not absolute determinants for surgical drainage in the stable pediatric ASCL patients. If patients show no clinical improvements despite appropriate second- and third-line antibiotics, patients should be carefully reevaluated and image-guided aspiration considered. PMID- 27553594 TI - A Unique Surgical Technique for Tracheostomy in Heterotopic Ossification: A Case Report. AB - OBJECTIVE: To describe a technique for tracheostomy in heterotopic ossification that has not yet been described in the literature. METHODS: We report a case of difficult tracheostomy while using conventional techniques in a 68-year-old patient who underwent mitral valve replacement requiring warfarin therapy three months prior. Imaging revealed heterotopic ossification overlying the trachea. A literature review was performed to identify similar cases or techniques. RESULTS: Extensive surgical planning was pursued after the initial attempted tracheostomy failed, and the airway was eventually accessed using a lighted intubation stylet for guidance and a drill. Heterotopic ossification has been described after orthopedic and abdominal surgeries. We identified one case report in the literature of tracheostomy performed in the setting of heterotopic ossification by an unspecified mechanism. There are few reported cases of tracheobronchial calcification in cardiac patients receiving warfarin therapy; however, these patients had characteristic imaging findings that were not consistent with those of our patient. CONCLUSIONS: We illustrate a safe and effective technique for tracheostomy in heterotopic ossification that has not been reported. Coordination with the anesthesia service was paramount for a successful operation. PMID- 27553595 TI - Can PFTS Differentiate PVFMD From Subglottic Stenosis? AB - OBJECTIVE: To determine if the results of routine spirometry and flow volume loops (Pulmonary Function Tests (PFTs)) can be used to distinguish Paradoxic Vocal Fold Movement Disorder (PVFMD) from Subglottic Stenosis (SGS). METHODS: PFT records and medical history of 49 patients with diagnosis of PVFMD and 39 patients with SGS were compared. Groups were then subdivided to compare PFTs in patients with and without smoking history or lung disease. RESULTS: Peak expiratory flow rate (PEFR) and Expiratory Disproportion Index (ratio of forced expiratory volume in 1 second (FEV1) over PEFR (FEV1/PEFR)) were both significantly different between patients with SGS and those with PVFMD (p<0.02). FEV1 was also significantly different, but only in the patients with no smoking history or lung disease (p<0.02). CONCLUSIONS: The findings suggest that spirometry can be a valuable tool in distinguishing SGS from PVFMD. Previous studies have shown the utility of PFTs for distinguishing SGS from pulmonary pathology, but this is the first study to exploit PFTs for distinction of SGS from PVFMD. Given that the flexible laryngoscopic exam used to diagnose PVFMD does not always visualize the subglottis completely, PFTs can be used to increase suspicion of SGS and direct further work-up. PMID- 27553596 TI - A Diagnostic Dilemma: Multiple Primary Intracranial Tumors Without Vestibular Schwannomas. AB - Sinonasal schwannomas with intracranial extension are exceedingly rare, with only 7 cases reported in the literature. Schwannomas can be isolated or multiple and are commonly associated with familial disorders such as neurofibromatosis 2 (NF 2) or familial schwannomatosis or in sporadic cases seen in sporadic schwannomatosis. Nearly all people with NF2 older than 30 years of age will have the hallmark of bilateral vestibular schwannomas (VS). This case highlights a reported case of an adult with separate primary intracranial tumors. We review the diagnostic criteria of NF2 and schwannomatosis, a recently described third variant of neurofibromatosis. In this case, we incorporate family history, histopathology, and the pathophysiology of both disorders to help determine a diagnosis for this patient. PMID- 27553597 TI - Design, Challenges, and Implications of Quality Improvement Projects Using the Electronic Medical Record: Case Study: A Protocol to Reduce the Burden of Postoperative Atrial Fibrillation. AB - Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery, which results in increased morbidity, mortality, length of stay, and hospital costs. We developed and followed a process map to implement a protocol to decrease POAF: (1) identify stakeholders and form a working committee, (2) formal literature and guideline review, (3) retrospective analysis of current institutional data, (4) data modeling to determine expected effects of change, (4) protocol development and implementation into the electronic medical record, and (5) ongoing review of data and protocol adjustment. Retrospective analysis demonstrated that POAF occurred in 29.8% of all cardiovascular surgery cases. Median length of stay was 2 days longer (P<0.001), and median total variable costs $2495 higher (P<0.001) in POAF patients. Modeling predicted that up to 60 cases of POAF and >$200 000 annually could be saved. A clinically based electronic medical record tool was implemented into the electronic medical record to aid preoperative clinic providers in identifying patients eligible for prophylactic amiodarone. Initial results during the 9-month period after implementation demonstrated a reduction in POAF in patients using the protocol, compared with those who qualified but did not receive amiodarone and those not evaluated (11.1% versus 38.7% and 38.8%; P=0.022); however, only 17.3% of patients used the protocol. A standardized methodological approach to quality improvement and electronic medical record integration has potential to significantly decrease the incidence of POAF, length of stay, and total variable cost in patients undergoing elective coronary artery bypass graft and valve surgeries. This framework for quality improvement interventions may be adapted to similar clinical problems beyond POAF. PMID- 27553598 TI - Clinical Interventions to Reduce Preventable Hospital Readmission After Percutaneous Coronary Intervention. AB - Hospital readmissions are common and costly and, in some cases, may be related to problems with care processes. We sought to reduce readmissions after percutaneous coronary intervention (PCI) in a large tertiary care facility through programs to target vulnerabilities predischarge, after discharge, and during re-presentation to the emergency department. During initial hospitalization, we assessed patients' readmission risk with a validated risk score and used a discharge checklist to ensure access to appropriate medications and close follow-up for high-risk patients. We also developed patient education videos about chest discomfort and heart failure. After discharge, we established a new follow-up clinic with cardiology fellows. A computerized system was developed to automatically notify cardiologists when patients presented to the emergency department within 30 days of PCI to enhance patient access to cardiology care in the emergency department. Early cardiologist assessment and assistance with triage was encouraged, and the emergency department used a risk stratification algorithm derived from a local database of patients to triage patients presenting with chest discomfort after PCI. We tracked the number of patients readmitted after PCI to our hospital. With our interventions, from 2011 to 2015, the index hospital readmission rate has declined from 9.6% to 5.3%. This program could provide tangible structural changes that can be implemented in other healthcare centers, both reducing the cost of care and improving the quality of care for patients with PCI. PMID- 27553601 TI - A bacterial infection by Vibrio harveyi causing heavy reduction of cultured lined seahorse Hippocampus erectus. PMID- 27553599 TI - Glycemic Control for Patients With Type 2 Diabetes Mellitus: Our Evolving Faith in the Face of Evidence. AB - BACKGROUND: We sought to determine the concordance between the accumulating evidence about the impact of tight versus less tight glycemic control in patients with type 2 diabetes mellitus since the publication of UKPDS (UK Prospective Diabetes Study) in 1998 until 2015 with the views about that evidence published in journal articles and practice guidelines. METHODS AND RESULTS: We searched in top general medicine and specialty journals for articles referring to glycemic control appearing between 2006 and 2015 and identified the latest practice guidelines. To summarize the evidence, we included all published systematic reviews and meta-analyses of contemporary randomized trials of glycemic control measuring patient-important microvascular and macrovascular outcomes, and completed a meta-analysis of their follow-up extensions. We identified 16 guidelines and 328 statements. The body of evidence produced estimates warranting moderate confidence. This evidence reported no significant impact of tight glycemic control on the risk of dialysis/transplantation/renal death, blindness, or neuropathy. In the past decade, however, most published statements (77%-100%) and guidelines (95%) unequivocally endorsed benefit. There is also no significant effect on all-cause mortality, cardiovascular mortality, or stroke; however, there is a consistent 15% relative-risk reduction of nonfatal myocardial infarction. Between 2006 and 2008, most statements (47%-83%) endorsed the benefit; after 2008 (ACCORD), only a minority (21%-36%) did. CONCLUSIONS: Discordance exists between the research evidence and academic and clinical policy statements about the value of tight glycemic control to reduce micro- and macrovascular complications. This discordance may distort priorities in the research and practice agendas designed to improve the lives of patients with type 2 diabetes mellitus. PMID- 27553600 TI - Lymphocytic, cytokine and transcriptomic profiles in peripheral blood of dogs with atopic dermatitis. AB - BACKGROUND: Canine atopic dermatitis (cAD) is a common chronic and pruritic skin disease in dogs. The development of cAD involves complex interactions between environmental antigens, genetic predisposition and a number of disparate cell types. The aim of the present study was to perform comprehensive analyses of peripheral blood of AD dogs in relation to healthy subjects in order to determine the changes which would be characteristic for cAD. RESULTS: The number of cells in specific subpopulations of lymphocytes was analyzed by flow cytometry, concentration of chosen pro- and anti-inflammatory cytokines (IL-4, IL-10, IL-13, TNF-alpha, TGF-beta1) was determined by ELISA; and microarray analysis was performed on RNA samples isolated from peripheral blood nuclear cells of AD and healthy dogs. The number of Th cells (CD3(+)CD4(+)) in AD and healthy dogs was similar, whereas the percentage of Tc (CD3(+)CD8(+)) and Treg (CD4(+)CD25(+) Foxp3(+)) cells increased significantly in AD dogs. Increased concentrations of IL-13 and TNF-alpha, and decreased levels of IL-10 and TGF-beta1 was observed in AD dogs. The level of IL-4 was similar in both groups of animals. Results of the microarray experiment revealed differentially expressed genes involved in transcriptional regulation (e.g., transcription factors: SMAD2, RORA) or signal transduction pathways (e.g., VEGF, SHB21, PROC) taking part in T lymphocytes lineages differentiation and cytokines synthesis. CONCLUSIONS: Results obtained indicate that CD8(+) T cells, beside CD4(+) T lymphocytes, contribute to the development of the allergic response. Increased IL-13 concentration in AD dogs suggests that this cytokine may play more important role than IL-4 in mediating changes induced by allergic inflammation. Furthermore, observed increase in Treg cells in parallel with high concentrations of TNF-alpha and low levels of IL-10 and TGF-beta1 in the peripheral blood of AD dogs point at the functional insufficiency of Treg cells in patients with AD. PMID- 27553602 TI - Accelerated hypofractionated radiation therapy (AHRT) for non-small-cell lung cancer: can we leave standard fractionation? AB - PURPOSE: To report interim results from a single-institution study conducted to assess accelerated hypofractionated radiotherapy (AHRT) delivered with 3D conformal radiotherapy in two groups of patients with non-small cell lung cancer: (1) patients with early stage disease unable to tolerate surgery and ineligible for stereotactic body radiation therapy, and (2) patients with locally advanced disease unsuitable for concurrent chemoradiotherapy. METHODS/PATIENTS: A total of 83 patients (51 stage I-II, 32 stage III) were included. Radiotherapy targets included the primary tumor and positive mediastinal areas identified on the pre treatment PET-CT. Mean age was 77.8 +/- 7.8 years. ECOG performance status (PS) was >=2 in 50.6 % of cases. Radiotherapy was delivered in daily fractions of 2.75 Gy to a total dose of 66 Gy (BED10 84 Gy). Acute and late toxicities were evaluated according to NCI CTC criteria. RESULTS: At a median follow-up of 42 months, median overall survival (OS) and cause-specific survival (CSS) were 23 and 36 months, respectively. On the multivariate analysis, PS [HR 4.14, p = 0.0001)], stage [HR 2.51, p = 0.005)], and maximum standardized uptake values (SUVmax) [HR 1.04, p = 0.04)] were independent risk factors for OS. PS [HR 5.2, p = 0.0001)] and stage [HR 6.3, p = 0.0001)] were also associated with CSS. No cases of severe acute or late treatment-related toxicities were observed. CONCLUSIONS: OS and CSS rates in patients treated with AHRT for stage I-II and stage III NSCLC were good. Treatment was well tolerated with no grade three or higher treatment-related toxicity. PS, stage, and SUV max were predictive for OS and CSS. PMID- 27553603 TI - Intratumoral heterogeneity of CD44v6 in rectal cancer. AB - PURPOSE: CD44v6 plays a controversial role in tumor progression and patient outcome in colorectal cancer by plenty of conflicting reports. The purpose of this study was to profile the intratumoral heterogeneity of CD44v6 in rectal cancer and investigate its role in lymph node metastasis. METHODS: Sixty patients were included in this study. Immunohistochemistry for CD44v6 was performed in normal mucosa, primary tumor, and lymph node metastasis with whole tissue sections. The staining intensity in tumor center and invasive front was separately measured. Sampling bias was evaluated by quantitative real-time PCR with 15 pairs of frozen tissues from different sites of the primary tumor. RESULTS: CD44v6 expression increased from normal mucosa to primary tumor to lymph node metastasis. Multiple intratumoral staining patterns was observed in primary tumor, and CD44v6 expression in invasive front was significantly higher than that in tumor center. In addition, mRNA expression levels differed across different geographical regions of the tumor. No association between CD44v6 expression and lymph node metastasis was revealed. CONCLUSIONS: Substantial intratumoral heterogeneity of CD44v6 exists in rectal cancer that impacts the outcome of individual studies. CD44v6 expression should be assessed in a more precise way with a specified staining pattern and in a designated location. PMID- 27553604 TI - Absence of significant adverse events following thalidomide administration in bitches diagnosed with mammary gland carcinomas. AB - The aim of the study was to evaluate the incidence of adverse events (AEs) in female dogs diagnosed with advanced clinical stage mammary gland neoplasms following treatment with thalidomide. A prospective analysis of 29 female dogs treated with a high dose (HD) of 20 mg/kg/day of thalidomide for three months followed by a low dose (LD) of 10 mg/kg/day of thalidomide for three months was performed. All patients underwent physical examination, complete blood count, serum biochemistry profile, thoracic radiographs, and abdominal ultrasound analysis before the treatment and after the HD and LD. Clinical AEs were absent in 16/29 (55.17 per cent) patients following HD. An initial 3-5 day period of somnolence was described in 4/29 (13.79 per cent), prolonged somnolence in 5/29 (17.24 per cent), a short period of somnolence lasting only a few hours in 3/29 (10.34 per cent), and difficulty to rouse was described in 5/29 (17.24 per cent) cases. Two patients (6.89 per cent) presented with prolonged somnolence that interfered with activities of daily living, resulting in anticipation of the dose reduction to the proposed LD after 15 days of the HD treatment. Following dose reduction, AE improvement was observed in all patients. Albeit remaining within the reference ranges, erythrocytes, haematocrit, total leucocyte count, neutrophils, lymphocytes, monocytes and gamma-glutamyltranspeptidase showed significant alteration associated to thalidomide treatment. PMID- 27553605 TI - Higher perceived risk of antimicrobials is related to lower antimicrobial usage among pig farmers in four European countries. AB - The prudent use of antimicrobials (AMs) should be widened in pig farming to reduce the risk of AM resistance (AMR) in human and veterinary medicine. It is therefore important to understand pig farmers' motivators and the barriers to AM usage (AMU) on their farms. The authors investigated pig farmers' self-estimated levels of AMU, their perceived benefits and risks and the need for AMs in a cross sectional survey in Belgium, France, Germany and Sweden. The authors also compared these perceptions between the four countries and related them to pig farmers' actual AMU. The results showed that farmers who used more AMs also estimated their own usage as higher. Farmers perceived many benefits but relatively few risks of AMU in pig farming. Some significant cross-country differences in farmers' perceptions were found, but they were relatively small. After controlling for country differences and farm differences, only perceived risks had a significant association with AMU. The authors therefore conclude that in order to promote prudent AMU, it seems most promising to focus on the structural differences in pig farming and veterinary medicine (e.g. legislation, role of the veterinarian) among countries. In addition, interventions which aim at reducing AMU should increase farmers' awareness of the risks of extensive AMU. PMID- 27553606 TI - The role of social capital and community belongingness for exercise adherence: An exploratory study of the CrossFit gym model. AB - This is the first study to measure the 'sense of community' reportedly offered by the CrossFit gym model. A cross-sectional study adapted Social Capital and General Belongingness scales to compare perceptions of a CrossFit gym and a traditional gym. CrossFit gym members reported significantly higher levels of social capital (both bridging and bonding) and community belongingness compared with traditional gym members. However, regression analysis showed neither social capital, community belongingness, nor gym type was an independent predictor of gym attendance. Exercise and health professionals may benefit from evaluating further the 'sense of community' offered by gym-based exercise programmes. PMID- 27553607 TI - 'Because it kind of falls in between, doesn't it? Like an acute thing and a chronic': The psychological experience of anaphylaxis in adulthood. AB - Anaphylaxis is a serious, rare condition increasing in prevalence. This study explored the psychological experience of adult-onset anaphylaxis from patient, family and staff perspectives. Semi-structured interviews were conducted with 12 participants. Two global themes emerged from thematic analysis: 'controllability' ('an unknown and distressing experience', 'the importance of control over triggers' and 'responsibility but no control: the impact on others') and 'conflict' ('rejecting illness identity', 'minimisation of risk', 'accessing specialist care: running in slow motion' and 'patient-centred versus service centred care'). Findings highlight the importance of perceived control and emphasise the presence of conflict in the experience of this complex, episodic condition. PMID- 27553608 TI - It's like a black woman's Charlie Brown moment: An autoethnography of being diagnosed with lupus. AB - This essay uses autoethnography to relate the experience of being diagnosed with lupus. By using my personal experiences and a discussion of illness and Black women's health, I critically examine larger critical race issues of race, gender, and the social barriers to health care. Specifically, the essay focuses on the ways in which race impacts my experiences with the healthcare system, from my own insecurities of being stereotyped to the ways that doctors interact with me. The essay is framed by popular quotes from Charlie Brown because they help mediate the very personal experiences I am recounting. PMID- 27553609 TI - Education differences in cancer fatalism: The role of information-seeking experiences. AB - Cancer fatalism is the belief that cancer is uncontrollable and lethal. Individuals with less education are more likely to hold fatalistic beliefs about cancer, but the mechanism accounting for the relationship is unknown. We tested whether negative health information seeking experiences explain this relationship. Structural equation modeling was used to test this relationship across three datasets from the Health Information National Trends Survey. Across all datasets, the model showed good fit: Cycle 1 (coefficient of determination = .11, comparative fit index = .96, root mean square error of approximation = .047), Cycle 2 (coefficient of determination = .06, comparative fit index = .96, root mean square error of approximation = .046), and Cycle 3 (coefficient of determination = .08, comparative fit index = .95, root mean square error of approximation = .052). The link between lower education level and higher cancer fatalism was partially mediated by negative health information seeking experiences. PMID- 27553610 TI - Utilization of Standardized Mental Health Assessments in Anthropological Research: Possibilities and Pitfalls. AB - In the past decade anthropologists working the boundary of culture, medicine, and psychiatry have drawn from ethnographic and epidemiological methods to interdigitate data and provide more depth in understanding critical health problems. But rarely do these studies incorporate psychiatric inventories with ethnographic analysis. This article shows how triangulation of research methods strengthens scholars' ability (1) to draw conclusions from smaller data sets and facilitate comparisons of what suffering means across contexts; (2) to unpack the complexities of ethnographic and narrative data by way of interdigitating narratives with standardized evaluations of psychological distress; and (3) to enhance the translatability of narrative data to interventionists and to make anthropological research more accessible to policymakers. The crux of this argument is based on two discrete case studies, one community sample of Nicaraguan grandmothers in urban Nicaragua, and another clinic-based study of Mexican immigrant women in urban United States, which represent different populations, methodologies, and instruments. Yet, both authors critically examine narrative data and then use the Center for Epidemiologic Studies Depression Scale to further unpack meaning of psychological suffering by analyzing symptomatology. Such integrative methodologies illustrate how incorporating results from standardized mental health assessments can corroborate meaning-making in anthropology while advancing anthropological contributions to mental health treatment and policy. PMID- 27553611 TI - Surgical Excision and Adjuvant Brachytherapy vs External Beam Radiation for the Effective Treatment of Keloids: 10-Year Institutional Retrospective Analysis. AB - BACKGROUND: Surgically excised keloids reportedly recur at a rate of >45%. Post excision radiation (RT) has been delivered via external beam radiotherapy (EBRT) or interstitial high dose rate (HDR) brachytherapy. Despite historical data showing 10% to 20% keloid recurrences with post-excision RT, there is a paucity of high-quality evidence comparing keloid recurrences between the two RT modalities. OBJECTIVES: We performed the largest single-institution case-control retrospective study (2004-2014) of keloid recurrence rates and complications between post-excision EBRT and HDR brachytherapy. METHODS: One-hundred and twenty eight patients, with 264 keloid lesions, were treated by excision alone (n = 28), post-excision EBRT (n = 197), or post-excision HDR brachytherapy (n = 39). Patient and keloid recurrence data were analyzed using mixed effect Cox regression modeling with a statistical threshold of P < .05. RESULTS: Fifty-four percent of keloids recurred after surgical excision alone (9-month median follow up); 19% of keloids recurred with post-excision EBRT (42-month median follow up); 23% of keloids recurred with post-excision brachytherapy (12-month median follow up). Adjuvant EBRT and brachytherapy each showed significant control of keloid recurrence compared to excision alone (P < .01). EBRT significantly delayed the time of keloid recurrence over brachytherapy by a mean difference of 2.5 years (P < .01). CONCLUSIONS: Post-excision RT shows significant reduction in keloid recurrence compared to excision alone. While the recurrence control rates are not statistically different between EBRT and brachytherapy, keloids treated with EBRT recurred significantly later than those treated by HDR brachytherapy by a mean of 2.5 years. Further workup with a randomized control study will help to refine optimal adjuvant RT treatment. LEVEL OF EVIDENCE 3. PMID- 27553612 TI - Successful Breast Reconstruction Despite Dislodgement of Tissue Expander Magnetic Ports. PMID- 27553613 TI - Is Office-Based Surgery Safe? Comparing Outcomes of 183,914 Aesthetic Surgical Procedures Across Different Types of Accredited Facilities. AB - BACKGROUND: There has been a dramatic rise in office-based surgery. However, due to wide variations in regulatory standards, the safety of office-based aesthetic surgery has been questioned. OBJECTIVES: This study compares complication rates of cosmetic surgery performed at office-based surgical suites (OBSS) to ambulatory surgery centers (ASCs) and hospitals. METHODS: A prospective cohort of patients undergoing cosmetic surgery between 2008 and 2013 were identified from the CosmetAssure database (Birmingham, AL). Patients were grouped by type of accredited facility where the surgery was performed: OBSS, ASC, or hospital. The primary outcome was the incidence of major complication(s) requiring emergency room visit, hospital admission, or reoperation within 30 days postoperatively. Potential risk factors including age, gender, body mass index (BMI), smoking, diabetes, type of procedure, and combined procedures were reviewed. RESULTS: Of the 129,007 patients (183,914 procedures) in the dataset, the majority underwent the procedure at ASCs (57.4%), followed by hospitals (26.7%) and OBSS (15.9%). Patients operated in OBSS were less likely to undergo combined procedures (30.3%) compared to ASCs (31.8%) and hospitals (35.3%, P < .01). Complication rates in OBSS, ASCs, and hospitals were 1.3%, 1.9%, and 2.4%, respectively. On multivariate analysis, there was a lower risk of developing a complication in an OBSS compared to an ASC (RR 0.67, 95% CI 0.59-0.77, P < .01) or a hospital (RR 0.59, 95% CI 0.52-0.68, P < .01). CONCLUSIONS: Accredited OBSS appear to be a safe alternative to ASCs and hospitals for cosmetic procedures. Plastic surgeons should continue to triage their patients carefully based on other significant comorbidities that were not measured in this present study. LEVEL OF EVIDENCE 3. PMID- 27553614 TI - An Easy, Efficient, and Safe Method for Intraoperative Digital Photography by Smartphone. PMID- 27553615 TI - Help-seeking in emerging adults with and without a history of mental health referral: a qualitative study. AB - BACKGROUND: Young people are generally reluctant to seek professional help when experiencing problems. However, past experience of services is often cited as increasing the intention to seek help, therefore those with a history of mental health referral may adopt more adaptive help seeking strategies. The current study investigated whether the pattern of different help seeking strategies and barriers to help seeking differed as a function of previous referral history. METHODS: Semi-structured interviews were conducted with 29 emerging adults (12 males, 17 females); 17 with a history of mental health referral and 12 without and analysed using thematic analysis. RESULTS: Overall, those with a referral to services were more likely than those without to rely on avoidant coping, especially techniques that depended upon suppression. This could help account for the increased use of strategies involving self-harm and substances in those with past referral. An exploration of barriers to help seeking showed those with a history of mental health referral were much more likely to self-stigmatise and this became attached to their sense of identity. CONCLUSIONS: Emerging adults with a history of referral are more likely to adopt avoidant coping strategies when dealing with problems and self-stigmatise to a greater degree than those without a history of referral. This suggests that current approaches to mental health in emerging adults are not decreasing the sense of stigma with potentially far-reaching consequences for the developing sense of self and choice of help seeking strategies. PMID- 27553616 TI - Postoperative carcinoembryonic antigen level has a prognostic value for distant metastasis and survival in rectal cancer patients who receive preoperative chemoradiotherapy and curative surgery: a retrospective multi-institutional analysis. AB - The cut-off value and prognostic significance of postoperative carcinoembryonic antigen (CEA) level in rectal cancer after preoperative chemoradiotherapy (CRT) and curative surgery are still unclear. 1559 rectal cancer patients staged with cT3-4N0-2M0 received preoperative CRT and total mesorectal excision (TME). CEA levels were measured before CRT and 3-4 weeks after surgery. Clinicopathologic factors that could be associated with tumor recurrence and patient survival were analyzed. The cumulative probability of tumor recurrence showed a steep increase with a cutoff value of 2.5 ng/mL for postoperative CEA level, and the gradient decreased as the CEA levels increased above 2.5 ng/mL. After a median follow-up time of 46.7 months, patients with postoperative CEA level >2.5 ng/mL had significantly lower relapse-free survival (RFS) (65.2 vs. 75.6 %, P < 0.001) and overall survival (OS) (78.1 vs. 88.3 %, P < 0.001) at 5 years than patients with postoperative CEA level <=2.5 ng/mL. On the multivariate analysis, postoperative CEA level was a significant prognostic factor for RFS (HR 1.561; 95 % CI 1.221 1.996; P < 0.001) and OS (HR 2.073; 95 % CI 1.498-2.869; P < 0.001). Postoperative CEA level independently affected RFS irrespective of pre-CRT CEA level. Postoperative CEA level was a significant predictor for distant recurrence (P = 0.004), but not for locoregional recurrence (P = 0.472). Postoperative CEA level >2.5 ng/ml is a predictor of distant metastasis and a negative prognostic factor for survival in rectal cancer patients who receive preoperative CRT and curative surgery. PMID- 27553618 TI - The impact of 2015 neuromyelitis optica spectrum disorders criteria on diagnostic rates. AB - BACKGROUND: The international panel for neuromyelitis optica (NMO) diagnosis has proposed diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD). OBJECTIVES: We assessed the impact of these criteria on diagnostic rates in a large cohort of patients. METHODS: We identified and applied the 2006 and 2015 criteria to all patients ( n = 176) seen in the NMO and non-multiple sclerosis central nervous system demyelination clinic (part of the UK NMO service) from January 2013 to May 2015. RESULTS: The 2006 criteria classified 63 of 176 (36%) patients as NMO. A total of 42 patients (67%) were aquaporin 4 (AQP4) immunoglobulin G (IgG) +ve and 21 (33%) AQP4 IgG -ve. The 2015 criteria classified 111 of 176 (63%) patients as NMOSD, of which 81 (73%) were AQP4 IgG +ve and 30 (27%) were AQP4 IgG -ve. There was an increase of 48 patients (76%) diagnosed as NMOSD using the new criteria. CONCLUSION: Application of the 2015 criteria led to a rise in diagnosis of NMOSD by 76%. The rise in the AQP4 IgG +ve group contributed 62% and the seronegative group contributed 14%. PMID- 27553617 TI - Family Structure and Child Health: Does the Sex Composition of Parents Matter? AB - The children of different-sex married couples appear to be advantaged on a range of outcomes relative to the children of different-sex cohabiting couples. Despite the legalization of same-sex marriage in the United States, whether and how this general pattern extends to the children of same-sex married and cohabiting couples is unknown. This study examines this question with nationally representative data from the 2004-2013 pooled National Health Interview Survey (NHIS). Results reveal that children in cohabiting households have poorer health outcomes than children in married households regardless of the sex composition of their parents. Children in same-sex and different-sex married households are relatively similar to each other on health outcomes, as are children in same-sex and different-sex cohabiting households. These patterns are not fully explained by socioeconomic differences among the four different types of families. This evidence can inform general debates about family structure and child health as well as policy interventions aiming to reduce child health disparities. PMID- 27553619 TI - Hepatitis B e Antigen Expression by Hepatitis B Virus Subgenotype A1 Relative to Subgenotypes A2 and D3 in Cultured Hepatocellular Carcinoma (Huh7) Cells. AB - BACKGROUND: Hepatitis B virus (HBV) is hyperendemic in southern Africa, with subgenotype A1 prevailing. The precore/core (preC/C) region of A1, encoding for hepatitis B e antigen (HBeAg), has unique sequence characteristics, differentiating it from subgenotypes A2 and D3. Our aim was to follow the expression of HBeAg in vitro by the three subgenotypes. METHODS: Huh7 cells were transfected with plasmids belonging to subgenotypes A1, A2, and D3. Using indirect immunofluorescence, the expression of HBeAg was followed, as was the activation of the unfolded protein response (UPR) and subsequent activation of apoptosis. RESULTS AND CONCLUSIONS: Following transfection with D3, HBeAg passed through the secretory pathway earlier than cells transfected with genotype A. Cells transfected with A1 showed a lower expression of the preC/C precursor in the secretory pathway and a higher co-localization in the nucleus. Cells transfected with A1 showed greater endoplasmic reticulum (ER) stress and an earlier, prolonged activation of the UPR seen by the higher activity of three ER localized transmembrane transducers (double-stranded RNA-dependent protein kinase like ER kinase, activating transcription factor 6, and inositol-requiring enzyme 1), on day 3 compared to day 5. Moreover, our study also found that cells transfected with A1 had increased apoptosis. PMID- 27553620 TI - Blastococcus capsensis sp. nov., isolated from an archaeological Roman pool and emended description of the genus Blastococcus, B. aggregatus, B. saxobsidens, B. jejuensis and B. endophyticus. AB - A novel Gram-reaction-positive actinobacterium, designated BMG 804T, was isolated from an archaeological Roman pool located in Gafsa, Tunisia. The strain grew as dry bright orange colonies at 30 degrees C and pH 6.0-8.0. It contained meso diaminopimelic acid in the cell wall. The whole-cell sugars consisted of glucose, rhamnose and ribose. Polar lipids present were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, an unidentified glycolipid and two unidentified phospholipids. MK-9(H4) was the predominant menaquinone. The fatty acid profile contained major amounts (>5 %) of C17 : 1omega8c, C16 : 1omega7c, iso-C15 : 0, iso-C16 : 0 and iso-C16 : 1H. The 16S rRNA gene sequence of BMG 804T showed 99.4 % as highest sequence similarity with Blastococcussaxobsidens. DNA-DNA hybridization between strain BMG 804T and B.saxobsidens DSM 44509T was 48.6+/-6.6 %. The G+C content of the DNA was 73.7 mol%. On the basis of the phenotypic and genotypic characteristics, including DNA DNA hybridization results, BMG 804T (=DSM 46835T=CECT 8876T) is proposed as the type strain of a novel species Blastococcuscapsensis sp. nov. Emended descriptions of the genus Blastococcus and the species Blastococcus aggregatus, B. saxobsidens, Blastococcus jejuensis and Blastococcus endophyticus are also proposed. PMID- 27553621 TI - Role of vitamin D receptor gene Cdx2 and Apa1 polymorphisms in prostate cancer susceptibility: a meta-analysis. AB - BACKGROUND: Vitamin D receptor (VDR) gene polymorphisms affect the risk of prostate cancer. However, studies investigating the relationship between VDR gene polymorphisms (Cdx2 and ApaI) and prostate cancer risk are equivocal. Therefore, we conducted a meta-analysis of all the studies to review the evidence available. METHODS: A comprehensive search of PubMed, EMBASE, and ISI Web of Science for studies published until September 2015 was conducted. Odds ratios (ORs) and 95 % confidence intervals (CIs) were analyzed to determine the association between VDR Cdx2 and ApaI polymorphisms, and prostate cancer risk. RESULTS: The meta-analysis included 10 studies involving 4979 cases and 4380 controls to analyze the VDR Cdx2 polymorphism. An additional 11 studies involving 2837 cases and 2884 controls were analyzed for the VDR ApaI polymorphism. Evidence failed to support the role of VDR Cdx2 and ApaI polymorphisms in prostate cancer. For Cdx2, the pooled OR was 1.11 (95 % CI = 0.93-1.33) for AA vs. GG genotypes, 0.97 (95 % CI = 0.88-1.06) for GA vs. AA genotypes, 0.99 (95 % CI = 0.91-1.08) for AA + GA vs. GG, and 1.12 (95 % CI = 0.95-1.31) for AA vs. GA + GG. No significant relationship was observed in any subgroup analysis based on ethnicity, controls, and Hardy-Weinberg equilibrium (HWE). ORs for the ApaI polymorphism were similar. CONCLUSIONS: VDR Cdx2 and ApaI polymorphisms are not associated with prostate cancer. Additional evidence is required to confirm this conclusion. PMID- 27553622 TI - Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScope(TM)) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study. AB - BACKGROUND: Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScopeTM) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScopeTM and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScopeTM and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. RESULTS: Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScopeTM and standard embryology. The EmbryoScopeTM, however, more than doubled embryology staff time (P < 0.0001). In Part B, embryos grown in the EmbyoScopeTM demonstrated significantly poorer day-3 quality (depending on embryo parameter between P = 0.005 and P = 0.01). Suspicion that conical culture dishes of the EmbryoScopeTM (EmbryoSlideTM) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation. CONCLUSIONS: Though due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well defined patient populations before the uncontrolled utilization of these instruments further expands. TRIAL REGISTRATION: NCT02246309 Registered September 18, 2014. PMID- 27553623 TI - Pulpal response following photo-biomodulation with a 904-nm diode laser: a double blind clinical study. AB - The aim of this study was to evaluate pulpal responses in healthy human teeth to photo-biomodulation therapy (PBMT) with 904-nm GaAs diode laser. The study followed a double-blind split mouth design, with a randomly selected maxillary first premolar acting as a sham-irradiated control tooth, and the contralateral tooth receiving active laser treatment. Two coded but otherwise identical laser probes (IrradiaTM, SpectraMedics Ltd., NC, USA) were used to deliver the sham (placebo) and laser radiation, with both the operator and patient unaware of each probe's identity. The selection of teeth for sham or laser irradiation was randomised for each treatment. Pulpal responses were assessed using electric pulp testing (EPT), 2 min prior to exposure, and immediately after laser irradiation (60 s, 30 mW average power, 25 Hz pulse frequency, 3.6 J/cm2). Treatment effects were analysed using the Wilcoxon-signed rank test. A total of 30 participants provided written informed consent. Majority of the participants (66.7 %) demonstrated an analgesic effect following PBMT (elevated EPT scores); however, nine participants (30 %) reported the lower EPT scores than the control. Both the treatment effects (stimulation and analgesia) were significant compared to the placebo. In most individuals, PBMT of healthy teeth with a 904-nm GaAs diode laser can induce analgesia, as witnessed by elevated EPT scores. A converse effect can occur in a minority of subjects. PMID- 27553624 TI - Nigella sativa (black cumin seed) as a biological detoxifier in diet contaminated with aflatoxin B1. AB - Aflatoxin B1 (AFB1 ) is a common feed contaminant that adversely affects bird performance and product quality. A total of 600 7-day-old quail chicks were randomly allotted to eight experimental groups in a completely randomized design with five replicate pens and 15 quails per pen. Experimental treatments including two levels of AFB1 (0 and 2.5 mg/kg) and 4 levels of Nigella sativa (NS) (0, 0.5, 1.0 and 1.5% of diet) were offered from 7 to 35 days of age to quail chicks. Although feeding of AFB1 impaired gain (G) and feed conversion ratio, dietary NS increased G (p < 0.05). Relative weight of bursa of Fabricius increased with incremental levels of NS (p < 0.05). AFB1 decreased the size of heart, but incremental levels of NS increased the relative weight of heart (p < 0.05). The liver hypertrophy was observed in birds receiving AFB1 (p < 0.05). The birds in AFB1 group had smaller testes than other groups (p < 0.05). Hematocrit value in birds fed AFB1 was lower than that in other groups (p < 0.05) and incremental levels of NS increased blood hematocrit (p < 0.05). Amount of malondialdehyde (MDA) in meat samples of the birds fed AFB1 was higher than those did not receive toxin but incremental levels of NS decreased the MDA concentration in affected birds (p < 0.05). AFB1 suppressed the humoral immunity of the birds while NS augmented the antibody titres against sheep red blood cell and Newcastle disease virus antigens (p < 0.05). AFB1 decreased lactic acid bacteria (LAB) and spore forming bacteria (SFB) but increased Escherichia coli (E. coli; p < 0.05). However, NS increased LAB and SFB but decreased the E. coli populations (p < 0.05). This study revealed that NS as a biological detoxifier could relatively attenuate the negative effects of AFB1 in quails. PMID- 27553625 TI - Stepwise iterative maximum likelihood clustering approach. AB - BACKGROUND: Biological/genetic data is a complex mix of various forms or topologies which makes it quite difficult to analyze. An abundance of such data in this modern era requires the development of sophisticated statistical methods to analyze it in a reasonable amount of time. In many biological/genetic analyses, such as genome-wide association study (GWAS) analysis or multi-omics data analysis, it is required to cluster the plethora of data into sub-categories to understand the subtypes of populations, cancers or any other diseases. Traditionally, the k-means clustering algorithm is a dominant clustering method. This is due to its simplicity and reasonable level of accuracy. Many other clustering methods, including support vector clustering, have been developed in the past, but do not perform well with the biological data, either due to computational reasons or failure to identify clusters. RESULTS: The proposed SIML clustering algorithm has been tested on microarray datasets and SNP datasets. It has been compared with a number of clustering algorithms. On MLL datasets, SIML achieved highest clustering accuracy and rand score on 4/9 cases; similarly on SRBCT dataset, it got for 3/5 cases; on ALL subtype it got highest clustering accuracy for 5/7 cases and highest rand score for 4/7 cases. In addition, SIML overall clustering accuracy on a 3 cluster problem using SNP data were 97.3, 94.7 and 100 %, respectively, for each of the clusters. CONCLUSIONS: In this paper, considering the nature of biological data, we proposed a maximum likelihood clustering approach using a stepwise iterative procedure. The advantage of this proposed method is that it not only uses the distance information, but also incorporate variance information for clustering. This method is able to cluster when data appeared in overlapping and complex forms. The experimental results illustrate its performance and usefulness over other clustering methods. A Matlab package of this method (SIML) is provided at the web-link http://www.riken.jp/en/research/labs/ims/med_sci_math/ . PMID- 27553626 TI - Evaluation of a risk-stratification strategy to improve primary care for low back pain: the MATCH cluster randomized trial protocol. AB - BACKGROUND: Despite numerous options for treating back pain and the increasing healthcare resources devoted to this problem, the prevalence and impact of back pain-related disability has not improved. It is now recognized that psychosocial factors, as well as physical factors, are important predictors of poor outcomes for back pain. A promising new approach that matches treatments to the physical and psychosocial obstacles to recovery, the STarT Back risk stratification approach, improved patients' physical function while reducing costs of care in the United Kingdom (UK). This trial evaluates implementation of this strategy in a United States (US) healthcare setting. METHODS: Six large primary care clinics in an integrated healthcare system in Washington State were block-randomized, three to receive an intensive quality improvement intervention for back pain and three to serve as controls for secular trends. The intervention included 6 one hour training sessions for physicians, 5 days of training for physical therapists, individualized and group coaching of clinicians, and integration of the STarT Back tool into the electronic health record. This prognostic tool uses 9 questions to categorize patients at low, medium or high risk of persistent disabling pain with recommendations about evidence-based treatment options appropriate for each subgroup. Patients at least 18 years of age, receiving primary care for non-specific low back pain, were invited to provide data 1-3 weeks after their primary care visit and follow-up data 2 months and 6 months (primary endpoint) later. The primary outcomes are back-related physical function and pain severity. Using an intention to treat approach, intervention effects on patient outcomes will be estimated by comparing mean changes at the 2 and 6 month follow-up between the pre- and post-implementation periods. The inclusion of control clinics permits adjustment for secular trends. Differences in change scores by intervention group and time period will be estimated using linear mixed models with random effects. Secondary outcomes include healthcare utilization and adherence to clinical guidelines. DISCUSSION: This trial will provide the first randomized trial evidence of the clinical effectiveness of implementing risk stratification with matched treatment options for low back pain in a United States health care delivery system. TRIAL REGISTRATION: NCT02286141. Registered November 5, 2014. PMID- 27553628 TI - Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as predictors of wound healing failure in head and neck reconstruction. AB - CONCLUSIONS: In microsurgical head and neck reconstruction, a higher rate of post operative wound complication could be predicted by a lower pre-operative neutrophil ratio (< 64.9%), neutrophil-lymphocyte ratio (NLR) (< 3.5), and platelet-lymphocyte ratio (PLR) (< 160). OBJECTIVES: To evaluate the predictor of post-operative wound complications in microsurgical head and neck reconstruction. METHODS: Patients who were undergoing tumor ablation and microsurgical reconstruction from April 2011 to March 2014 were analyzed retrospectively. The pre-operative hematological data, age, sex, co-morbidities, body mass index (BMI), adjuvant therapies, smoking, operation time, blood loss, total protein, T stage, and Anesthesiologists Performance Status (ASA-PS) score were collected. Cases of post-operative wound healing failure were reviewed. RESULTS: One hundred and three consecutive patients were enrolled. Among these, the results of 77 patients who were younger than 70 years of age were analyzed. The distributions of the neutrophil ratio (p = .0005), lymphocyte ratio (p = .0166), monocyte ratio (p = .0341), NLR (p = .005), and PLR (p = .008) differed significantly between the patients with and without post-operative wound healing failure. Neutrophil ratio, NLR, and PLR cut-off values of 64.9, 3.5, and 160 were significantly associated with the rate of wound healing failure rate (p = .0002, .00021, .0042, respectively). PMID- 27553627 TI - High prevalence of advanced colorectal neoplasia in the Thai population: a prospective screening colonoscopy of 1,404 cases. AB - BACKGROUND: Increasing morbidity and mortality from colorectal cancer is evident in recent years in the developing Asian nations. Particularly in Thailand and most neighbouring low-income countries, screening colonoscopy is not yet recommended nor implemented at the national policy level. METHODS: Screening colonoscopy was offered to 1,500 healthy volunteers aged 50-65 years old who were registered into the program between July 2009 and June 2010. Biopsy and surgery was performed depending on the identified lesions. Fecal immunochemical tests (FIT) were additionally performed for comparison with colonoscopy. RESULTS: There were 1,404 participants who underwent colonoscopy. The mean age of the cohort was 56.9 +/- 4.2 years and 69.4 % were females. About 30 % (411 cases) of all colonoscopies had abnormal colonoscopic findings, and of these, 256 cases had adenomatous polyps. High risk adenomas (villous or tubulovillous or high grade dysplasia or size > 1 cm or > 3 adenomatous polyps) were found in 98 cases (7 %), low risk adenoma in 158 cases (11.3 %), and hyperplastic polyps in 119 cases (8.5 %). Eighteen cases (1.3 %) had colorectal cancer and 90 % of them (16 cases) were non-metastatic including five stage 0 cases, seven stage I cases, and four stage IIA cases. Only two cases had metastasis: one to regional lymph nodes (stage IIIB) and another to other organs (stage IVA). The most common cancer site was the distal intestine including rectum (7 cases, 38.9 %) and sigmoid colon (7 cases, 38.9 %). Ten colorectal cancer cases had positive FIT whereas 8 colorectal cancer cases were FIT-negative. The sensitivity and specificity of FIT was 55.6 % and 96.2 %, respectively, while the positive predictive value was 16.4 % and negative predictive value was 99.4 %. The overall survival of colorectal cancer cases at 5-year was 83.3 %. CONCLUSION: High prevalence of colorectal cancer and high-risk adenoma was found in the Thai population aged 50-65 years old by screening colonoscopy. FIT was not sensitive enough to detect colorectal cancer in this asymptomatic cohort. Integration of screening colonoscopy into the national cancer screening program should be implemented to detect early cases of advanced colorectal neoplasia and improve survival of colorectal cancer patients in Thailand. PMID- 27553629 TI - Detecting gender before you know it: How implementation intentions control early gender categorization. AB - Gender categorization is highly automatic. Studies measuring ERPs during the presentation of male and female faces in a categorization task showed that this categorization is extremely quick (around 130ms, indicated by the N170). We tested whether this automatic process can be controlled by goal intentions and implementation intentions. First, we replicated the N170 modulation on gender incongruent faces as reported in previous research. This effect was only observed in a task in which faces had to be categorized according to gender, but not in a task that required responding to a visual feature added to the face stimuli (the color of a dot) while gender was irrelevant. Second, it turned out that the N170 modulation on gender-incongruent faces was altered if a goal intention was set that aimed at controlling a gender bias. We interpret this finding as an indicator of nonconscious goal pursuit. The N170 modulation was completely absent when this goal intention was furnished with an implementation intention. In contrast, intentions did not alter brain activity at a later time window (P300), which is associated with more complex and rather conscious processes. In line with previous research, the P300 was modulated by gender incongruency even if individuals were strongly involved in another task, demonstrating the automaticity of gender detection. We interpret our findings as evidence that automatic gender categorization that occurs at a very early processing stage can be effectively controlled by intentions. PMID- 27553630 TI - Chronic phenytoin treatment reduces rat carotid body chemosensory responses to acute hypoxia. AB - Ventilation is peripherally controlled by afferent activity arising from the peripheral chemoreceptors. In the rat, chemosensory activity is conveyed to the central nervous system through axons of neurons located in the nodose-petrosal jugular-complex. These neurons have distinct electrophysiological properties, including a persistent Na+ current. Acute blockade of this current with phenytoin and other anti-epileptic drugs reduces normoxic chemosensory activity and responses to acute hypoxia. However, because anti-epileptic therapy is prolonged and there is no information on the effects of chronic phenytoin treatment on peripheral chemosensory activity, we studied the effects of long-lasting phenytoin treatment (~25 days) on afferent chemosensory activity, on a wide range of oxygen inspiratory fractions. Osmotic pumps containing dissolved phenytoin (166mg/mL) or vehicle (daily flow: 60uL) were implanted subcutaneously in male adult Sprague Dawley rats. At the end of the treatment, the animals were anesthetized and carotid sinus nerve activity was recorded in vivo. Afferent chemosensory activity in normoxia was not significantly different between control (71.2+/-2.2Hz) and phenytoin treated (95.4+/-2.1Hz) rats. In contrast, carotid body chemosensory responses to acute hypoxic challenges were markedly reduced in phenytoin treated rats, specifically in the lowest part of the hypoxic range (control 133.5+/-18.0Hz vs phenytoin treated 50.2+/-29.4, at 5% FIO2). Chronic phenytoin treatment severely impaired the chemosensory responses to acute hypoxia, suggesting that long-term phenytoin treatment in patients may result in a reduced peripheral respiratory drive together with a reduction in the respiratory responses to hypoxic challenges. PMID- 27553631 TI - Neural correlates of verbal joint action: ERPs reveal common perception and action systems in a shared-Stroop task. AB - Recent social-cognitive research suggests that the anticipation of co-actors' actions influences people's mental representations. However, the precise nature of such representations is still unclear. In this study we investigated verbal joint representations in a delayed Stroop paradigm, where each participant responded to one color after a short delay. Participants either performed the task as a single actor (single-action, Experiment 1), or they performed it together (joint-action, Experiment 2). We investigated effects of co-actors' actions on the ERP components associated with perceptual conflict (Go N2) and response selection (P3b). Compared to single-action, joint-action reduced the N2 amplitude congruency effect when participants had to respond (Go trials), indicating that representing a co-actor's utterance helped to dissociate action codes and attenuated perceptual conflict for the responding participant. Yet, on NoGo trials the centro-parietal P3 (P3b) component amplitude increased for joint action, suggesting that participants mapped the stimuli onto the co-actor's upcoming response as if it were their own response. We conclude that people represent others' utterances similarly to the way they represent their own utterances, and that shared perception-action codes for self and others can sometimes reduce, rather than enhance, perceptual conflict. PMID- 27553632 TI - Effects of ZnO nanoparticle-coated packaging film on pork meat quality during cold storage. AB - BACKGROUND: There has been limited research on the use of ZnO nanoparticle-coated film for the quality preservation of pork meat under low temperature. In the present study, ZnO nanoparticles were mixed with sodium carboxymethyl cellulose (CMC-Na) to form a nanocomposite film, to investigate the effect of ZnO nanoparticle-coated film on pork meat quality and the growth of bacteria during storage under low temperature. RESULTS: When ZnO nanoparticle-coated film was used as the packaging material for pork meat for 14 days of cold storage at 4 degrees C, the results demonstrated a significant effect on restricting the increases in total volatile basic nitrogen and pH levels, limiting the decreases of lightness (increased L* value) and redness (increased a* value), and maintaining the water-holding capacity compared to the control pork samples (P < 0.05). The present study also discovered that the ZnO nanoparticle-coated film restrained the increase in total plate count (TPC). When Staphylococcus aureus was used as the representative strain, scanning electron microscopy revealed that ZnO nanoparticles increased the occurrence of cell membrane rupture under cold conditions. CONCLUSION: ZnO nanoparticle-coated film helps retain the quality of pork meat during cold storage by increasing the occurrence of microorganism injury. (c) 2016 Society of Chemical Industry. PMID- 27553633 TI - An intact plastid genome is essential for the survival of colorless Euglena longa but not Euglena gracilis. AB - Euglena gracilis growth with antibacterial agents leads to bleaching, permanent plastid gene loss. Colorless Euglena (Astasia) longa resembles a bleached E. gracilis. To evaluate the role of bleaching in E. longa evolution, the effect of streptomycin, a plastid protein synthesis inhibitor, and ofloxacin, a plastid DNA gyrase inhibitor, on E. gracilis and E. longa growth and plastid DNA content were compared. E. gracilis growth was unaffected by streptomycin and ofloxacin. Quantitative PCR analyses revealed a time dependent loss of plastid genes in E. gracilis demonstrating that bleaching agents produce plastid gene deletions without affecting cell growth. Streptomycin and ofloxacin inhibited E. longa growth indicating that it requires plastid genes to survive. This suggests that evolutionary divergence of E. longa from E. gracilis was triggered by the loss of a cytoplasmic metabolic activity also occurring in the plastid. Plastid metabolism has become obligatory for E. longa cell growth. A process termed "intermittent bleaching", short term exposure to subsaturating concentrations of reversible bleaching agents followed by growth in the absence of a bleaching agent, is proposed as the molecular mechanism for E. longa plastid genome reduction. Various non-photosynthetic lineages could have independently arisen from their photosynthetic ancestors via a similar process. PMID- 27553634 TI - Rolling-circle amplification of centromeric Helitrons in plant genomes. AB - The unusual eukaryotic Helitron transposons can readily capture host sequences and are, thus, evolutionarily important. They are presumed to amplify by rolling circle replication (RCR) because some elements encode predicted proteins homologous to RCR prokaryotic transposases. In support of this replication mechanism, it was recently shown that transposition of a bat Helitron generates covalently closed circular intermediates. Another strong prediction is that RCR should generate tandem Helitron concatemers, yet almost all Helitrons identified to date occur as solo elements in the genome. To investigate alternative modes of Helitron organization in present-day genomes, we have applied the novel computational tool HelitronScanner to 27 plant genomes and have uncovered numerous tandem arrays of partially decayed, truncated Helitrons in all of them. Strikingly, most of these Helitron tandem arrays are interspersed with other repeats in centromeres. Many of these arrays have multiple Helitron 5' ends, but a single 3' end. The number of repeats in any one array can range from a handful to several hundreds. We propose here an RCR model that conforms to the present Helitron landscape of plant genomes. Our study provides strong evidence that plant Helitrons amplify by RCR and that the tandemly arrayed replication products accumulate mostly in centromeres. PMID- 27553635 TI - A short-term extremely low frequency electromagnetic field exposure increases circulating leukocyte numbers and affects HPA-axis signaling in mice. AB - There is still uncertainty whether extremely low frequency electromagnetic fields (ELF-EMF) can induce health effects like immunomodulation. Despite evidence obtained in vitro, an unambiguous association has not yet been established in vivo. Here, mice were exposed to ELF-EMF for 1, 4, and 24 h/day in a short-term (1 week) and long-term (15 weeks) set-up to investigate whole body effects on the level of stress regulation and immune response. ELF-EMF signal contained multiple frequencies (20-5000 Hz) and a magnetic flux density of 10 MUT. After exposure, blood was analyzed for leukocyte numbers (short-term and long-term) and adrenocorticotropic hormone concentration (short-term only). Furthermore, in the short-term experiment, stress-related parameters, corticotropin-releasing hormone, proopiomelanocortin (POMC) and CYP11A1 gene-expression, respectively, were determined in the hypothalamic paraventricular nucleus, pituitary, and adrenal glands. In the short-term but not long-term experiment, leukocyte counts were significantly higher in the 24 h-exposed group compared with controls, mainly represented by increased neutrophils and CD4 +/- lymphocytes. POMC expression and plasma adrenocorticotropic hormone were significantly lower compared with unexposed control mice. In conclusion, short-term ELF-EMF exposure may affect hypothalamic-pituitary-adrenal axis activation in mice. Changes in stress hormone release may explain changes in circulating leukocyte numbers and composition. Bioelectromagnetics. 37:433-443, 2016. (c) 2016 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc. PMID- 27553636 TI - Psychiatric history, post-discharge distress, and personality characteristics among incident female cases of takotsubo cardiomyopathy: A case-control study. AB - BACKGROUND: The role of psychological factors in the onset of takotsubo cardiomyopathy (TC) is still controversial. Associations with previous psychiatric conditions are registry-based; associations with personality characteristics and psychological sequelae of TC have been largely unexplored. This case-control study sought to study pre-admission psychiatric morbidity, personality traits, and post-discharge distress in incident cases of TC. METHODS: TC cases (Mayo clinic criteria) and acute myocardial infarction (MI) controls were recruited among women admitted to two Emergency Departments in New England. Healthy controls (HC) were recruited from a volunteers' registry. Preadmission psychiatric history (DSM-IV-TR) was abstracted from the medical record. PTSD symptoms (Impact of Events Scale); distress (Hospital Anxiety and Depression Scale); perceived stress (PS scale) and personality traits (optimism; hostility, type D personality) were collected via phone interview one month after discharge. RESULTS: From March 2013 through October 2015, 107 participants (45 TC, 32 MI and 30 HC) were enrolled. The prevalence of preadmission anxiety disorders was 24.4% in TC, 9.4% in MI, and 0 in HC (p = 0.007) while that of mood disorders was similar across groups. TC had higher psychological distress, perceived stress, and PTSD symptoms post-discharge vs. MI and HC. In adjusted models, PTSD symptoms remained higher in TC vs. MI (b = 0.55, p < 0.05) and vs. HC (b = 0.92, p < 0.01). Optimism and hostility scores were similar across groups, while type D (social inhibition) scores were higher in TC and MI vs. HC. CONCLUSIONS: Preadmission anxiety, but not depression, was associated with the occurrence of TC. High distress and PTSD symptoms post-discharge indicate that TC women may be at risk for poor psychological adjustment. PMID- 27553637 TI - Ultra-Long Crystalline Red Phosphorus Nanowires from Amorphous Red Phosphorus Thin Films. AB - Heating red phosphorus in sealed ampoules in the presence of a Sn/SnI4 catalyst mixture has provided bulk black phosphorus at much lower pressures than those required for allotropic conversion by anvil cells. Herein we report the growth of ultra-long 1D red phosphorus nanowires (>1 mm) selectively onto a wafer substrate from red phosphorus powder and a thin film of red phosphorus in the present of a Sn/SnI4 catalyst. Raman spectra and X-ray diffraction characterization suggested the formation of crystalline red phosphorus nanowires. FET devices constructed with the red phosphorus nanowires displayed a typical I-V curve similar to that of black phosphorus and a similar mobility reaching 300 cm(2) V(-1) s with an Ion /Ioff ratio approaching 10(2) . A significant response to infrared light was observed from the FET device. PMID- 27553638 TI - Altered glycogen metabolism causes hepatomegaly following an Atg7 deletion. AB - Autophagy is a lysosomal degradation process involved in the turnover of organelles or other cell constituents, in providing sources for energy production under starving conditions and in cell metabolism. A key protein in the macroautophagic machinery is the autophagy-related protein (Atg) 7. Constitutive deletion of Atg7 is lethal at birth. A conditional deletion of Atg7 in hepatocytes leads to hepatomegaly and in aged animals to liver tumors. With this study, we aim at analyzing the hepatomegaly development in more detail. The 3- to 4-fold enlargement of the liver takes place between days 25 and 35 after birth (P25-P35) and persists at least until P90. This is accompanied by a change in the expression of enzymes involved in the glycogen/glucose metabolism. While glycogen synthesis is inhibited, glucose is preferentially kept as glucose-6-phosphate inside the cells, inducing a swelling of the cells caused by hyperosmolarity. An increase of lipogenic enzymes suggests that glucose-6-phosphate is delivered to lipogenic pathways, which is supported by the occurrence of a steatosis around P30. The development of hepatomegaly is accompanied by a polyploidisation of hepatocytes, an enhanced expression of genes related to inflammatory processes and an infiltration of macrophages and granulocytes. Our data provide evidence that the attenuation of macroautophagy in hepatocytes leads to a glucose retention that causes cell swelling. The resulting hepatomegaly, which develops in a time interval of about 10 days, perturbs liver perfusion and induces an inflammatory reaction together with polyploidisation. PMID- 27553639 TI - Spatial expression of components of a calcitonin receptor-like receptor (CRL) signalling system (CRL, calcitonin gene-related peptide, adrenomedullin, adrenomedullin-2/intermedin) in mouse and human heart valves. AB - Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling. Accumulating evidence suggests an important role of calcitonin receptor-like receptor (CRL) signalling in preventing heart damage under several pathological conditions. Thus we investigate the existence of a putative CRL signalling system in mouse and human heart valves by real-time RT-PCR, laser-assisted microdissection, immunofluorescence and NADPH-diaphorase histochemistry. Mouse and human heart valves expressed mRNAs for the CRL ligands adrenomedullin (AM), adrenomedullin-2 (AM-2) and calcitonin gene-related peptide (CGRP) and for their receptor components, i.e., CRL and receptor-activity-modifying proteins 1-3. Immunofluorescence analysis revealed AM-, AM-2- and CRL-immunolabelling in endothelial cells and VIC, whereas CGRP immunoreactivity was restricted to nerve fibres and some endothelial cells. Nitric oxide synthase activity, as demonstrated by NADPH-diaphorase histochemistry, was shown mainly in valvular endothelial cells in mice, whereas in human aortic valves, VIC and smooth muscle cells were positive. Our results showed the presence of an intrinsic AM/AM-2/CGRP signalling system in murine and human heart valves with distinct cellular localization, suggesting its involvement in the regulation of valve stiffness and ECM production and turnover. PMID- 27553641 TI - Pharmacological Value of Murine Delayed-type Hypersensitivity Arthritis: A Robust Mouse Model of Rheumatoid Arthritis in C57BL/6 Mice. AB - In this MiniReview, we summarize the body of knowledge on the delayed-type hypersensitivity arthritis (DTHA) model, a recently developed arthritis model with 100% incidence, low variation and synchronized onset in C57BL/6 (B6) mice, and compare it to other murine arthritis models. It is desirable to have robust arthritis models in B6 mice, as many transgene strains are bred on this background. However, several of the most widely used mouse model of arthritis cannot be induced in B6 mice without the drawback of lower incidence, reduced severity and higher variation, if at all. DTHA is induced by modifying a classical methylated bovine serum albumin (mBSA)-induced DTH response by administering a cocktail of anti-type II collagen antibodies (anti-CII) between immunization and challenge. Arthritis affects one, predefined paw in which acute inflammation and severe arthritis rapidly develop and peak after 4-7 days. Disease is self-resolving over the course of around 3 weeks. Disease manifestations resemble those seen in other arthritis models and include bone erosion, cartilage destruction, oedema, pannus and new bone formation. Induction of DTHA is dependent on CD4+ T cells while B cells are dispensable. The DTHA model is set apart from other murine arthritis models in that it can be induced in B6 mice with 100% incidence and with high and consistent severity. This is the clearest advantage of the model, as the mechanisms of disease and clinical manifestations can be found in other arthritis models. The model holds potential for future modifications that may improve the lack of chronicity. PMID- 27553640 TI - Psychotropic drug dispensing in people with and without cancer in France. AB - PURPOSE: To compare annual and monthly prevalence of psychotropic drug (PD) dispensing and the number and duration of psychotropic treatment episodes among people with and without cancer over a 2-year follow-up. METHODS: We studied the following two cohorts of adult patients affiliated with the National Health Insurance Fund (NHIF): cancer patients followed for 2 years after diagnosis and individuals without cancer matched to cancer patients. Using information about anxiolytic, hypnotic, antidepressant, and antipsychotic dispensing in community pharmacies, we applied conditional log-binomial regressions to estimate adjusted relative risks for monthly dispensing of PDs. RESULTS: Annual prevalence of PD dispensing-all categories included-among cancer patients was significantly higher for almost all the categories we studied than among individuals without cancer. Monthly prevalence of anxiolytic/hypnotic dispensing started to rise several months before diagnosis and peaked immediately after. Among patients with cancer and their matched controls, treatment duration exceeded 1 month for hypnotics in 40 and 35 %, respectively (p < 0.01), and 3 months for anxiolytics in 23 and 23 % (p = 0.8); it was less than 6 months for antidepressants in 76 and 75 % (p = 0.5). CONCLUSIONS: Prevalence of psychotropic treatment was higher among cancer patients than among persons without cancer. Psychotropic treatment duration was not in line with recommendations for significant fractions of cancer patients or their controls. IMPLICATIONS FOR CANCER SURVIVORS: Training of health professionals involved in cancer supportive care should be reinforced and specific guidelines developed to help them address psychological distress of cancer survivors. PMID- 27553642 TI - Exercise interventions for patients with gynaecological cancer: a systematic review and meta-analysis. AB - BACKGROUND: People with gynaecological cancer commonly suffer from physical and psychological symptoms related to their cancer and cancer treatment. OBJECTIVE: To evaluate and synthesise the evidence examining the effect of interventions with an exercise component for females with gynaecological cancer. DATA SOURCES: Medline, CINAHL, EMBASE, PubMed, PEDro, PsycINFO and Cochrane Library were searched systematically in September 2014. STUDY SELECTION: Randomised controlled trials were included if they investigated the effects of interventions with an exercise component in patients with gynaecological cancer. STUDY APPRAISAL: Two reviewers independently assessed the risk of bias of studies using the PEDro scale. RESULTS: Seven randomised controlled trials on five patient groups involving 221 participants were included. The mean PEDro score was 5.3 (standard deviation 1.5) out of 10. Compared with control groups, the intervention groups showed significantly greater improvements in physical activity levels and body mass index. No significant effects were found for fatigue, depression and health related quality of life. A meta-analysis of functional exercise capacity and muscle strength was not possible due to insufficient data in the included trials. LIMITATIONS: The majority of studies provided exercise as part of multicomponent intervention programmes. CONCLUSIONS: Interventions with an exercise component appear to be effective at improving physical activity levels and body mass index among patients with gynaecological cancer. Further research is required to examine the effects of exercise interventions alone in this population. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014014019. PMID- 27553643 TI - Physiotherapy students' perceptions and experiences of clinical prediction rules. AB - OBJECTIVES: Clinical reasoning can be difficult to teach to pre-professional physiotherapy students due to their lack of clinical experience. It may be that tools such as clinical prediction rules (CPRs) could aid the process, but there has been little investigation into their use in physiotherapy clinical education. This study aimed to determine the perceptions and experiences of physiotherapy students regarding CPRs, and whether they are learning about CPRs on clinical placement. DESIGN: Cross-sectional survey using a paper-based questionnaire. PARTICIPANTS: Final year pre-professional physiotherapy students (n=371, response rate 77%) from five universities across five states of Australia. RESULTS: Sixty percent of respondents had not heard of CPRs, and a further 19% had not clinically used CPRs. Only 21% reported using CPRs, and of these nearly three quarters were rarely, if ever, learning about CPRs in the clinical setting. However most of those who used CPRs (78%) believed CPRs assisted in the development of clinical reasoning skills and none (0%) was opposed to the teaching of CPRs to students. The CPRs most commonly recognised and used by students were those for determining the need for an X-ray following injuries to the ankle and foot (67%), and for identifying deep venous thrombosis (63%). CONCLUSIONS: The large majority of students in this sample knew little, if anything, about CPRs and few had learned about, experienced or practiced them on clinical placement. However, students who were aware of CPRs found them helpful for their clinical reasoning and were in favour of learning more about them. PMID- 27553644 TI - Redesigning healthcare to fit with people. PMID- 27553645 TI - Views of Cohort Study Participants about Returning Research Results in the Context of Precision Medicine. AB - BACKGROUND: The practice of biorepository-based genetics research raises questions related to what ethical obligations researchers have to their participants. It is important to explore and include the thoughts of current biorepository participants as we move forward with this type of research. METHODS: Thirty participants (17 cancer patients, 7 cancer-free controls, and 6 relatives) were drawn from the Northwest Cancer Genetics Registry and participated in qualitative interviews lasting between 45 and 90 min. Topics explored in this study include which types of genetic test results participants of large biorepositories expect and would like to receive from research analyzing their samples, as well as thoughts on best practice for conducting this type of research. RESULTS: Cancer cases, controls, and first-degree relatives have differing views on what results they would like to receive from biorepository based research. Participants across all groups attempted to balance the costs and benefits of returning individual research results. DISCUSSION: In the wake of precision medicine, it is important to describe the range of ways participants in large biorepositories both think and talk about the utilization of their specimens for genetics research. PMID- 27553647 TI - Unified Theory for Decoding the Signals from X-Ray Florescence and X-Ray Diffraction of Mixtures. AB - For research and development or for solving technical problems, we often need to know the chemical composition of an unknown mixture, which is coded and stored in the signals of its X-ray fluorescence (XRF) and X-ray diffraction (XRD). X-ray fluorescence gives chemical elements, whereas XRD gives chemical compounds. The major problem in XRF and XRD analyses is the complex matrix effect. The conventional technique to deal with the matrix effect is to construct empirical calibration lines with standards for each element or compound sought, which is tedious and time-consuming. A unified theory of quantitative XRF analysis is presented here. The idea is to cancel the matrix effect mathematically. It turns out that the decoding equation for quantitative XRF analysis is identical to that for quantitative XRD analysis although the physics of XRD and XRF are fundamentally different. The XRD work has been published and practiced worldwide. The unified theory derives a new intensity-concentration equation of XRF, which is free from the matrix effect and valid for a wide range of concentrations. The linear decoding equation establishes a constant slope for each element sought, hence eliminating the work on calibration lines. The simple linear decoding equation has been verified by 18 experiments. PMID- 27553646 TI - Gene Duplication and Gene Expression Changes Play a Role in the Evolution of Candidate Pollen Feeding Genes in Heliconius Butterflies. AB - Heliconius possess a unique ability among butterflies to feed on pollen. Pollen feeding significantly extends their lifespan, and is thought to have been important to the diversification of the genus. We used RNA sequencing to examine feeding-related gene expression in the mouthparts of four species of Heliconius and one nonpollen feeding species, Eueides isabella We hypothesized that genes involved in morphology and protein metabolism might be upregulated in Heliconius because they have longer proboscides than Eueides, and because pollen contains more protein than nectar. Using de novo transcriptome assemblies, we tested these hypotheses by comparing gene expression in mouthparts against antennae and legs. We first looked for genes upregulated in mouthparts across all five species and discovered several hundred genes, many of which had functional annotations involving metabolism of proteins (cocoonase), lipids, and carbohydrates. We then looked specifically within Heliconius where we found eleven common upregulated genes with roles in morphology (CPR cuticle proteins), behavior (takeout-like), and metabolism (luciferase-like). Closer examination of these candidates revealed that cocoonase underwent several duplications along the lineage leading to heliconiine butterflies, including two Heliconius-specific duplications. Luciferase-like genes also underwent duplication within lepidopterans, and upregulation in Heliconius mouthparts. Reverse-transcription PCR confirmed that three cocoonases, a peptidase, and one luciferase-like gene are expressed in the proboscis with little to no expression in labial palps and salivary glands. Our results suggest pollen feeding, like other dietary specializations, was likely facilitated by adaptive expansions of preexisting genes-and that the butterfly proboscis is involved in digestive enzyme production. PMID- 27553648 TI - Redox Imaging Using Cardiac Myocyte-Specific Transgenic Biosensor Mice. AB - RATIONALE: Changes in redox potentials of cardiac myocytes are linked to several cardiovascular diseases. Redox alterations are currently mostly described qualitatively using chemical sensors, which however do not allow quantifying redox potentials, lack specificity, and the possibility to analyze subcellular domains. Recent advances to quantitatively describe defined redox changes include the application of genetically encoded redox biosensors. OBJECTIVE: Establishment of mouse models, which allow the quantification of the glutathione redox potential (EGSH) in the cytoplasm and the mitochondrial matrix of isolated cardiac myocytes and in Langendorff-perfused hearts based on the use of the redox sensitive green fluorescent protein 2, coupled to the glutaredoxin 1 (Grx1 roGFP2). METHODS AND RESULTS: We generated transgenic mice with cardiac myocyte restricted expression of Grx1-roGFP2 targeted either to the mitochondrial matrix or to the cytoplasm. The response of the roGFP2 toward H2O2, diamide, and dithiothreitol was titrated and used to determine the EGSH in isolated cardiac myocytes and in Langendorff-perfused hearts. Distinct EGSH were observed in the cytoplasm and the mitochondrial matrix. Stimulation of the cardiac myocytes with isoprenaline, angiotensin II, or exposure to hypoxia/reoxygenation additionally underscored that these compartments responded independently. A compartment specific response was also observed 3 to 14 days after myocardial infarction. CONCLUSIONS: We introduce redox biosensor mice as a new tool, which allows quantification of defined alterations of EGSH in the cytoplasm and the mitochondrial matrix in cardiac myocytes and can be exploited to answer questions in basic and translational cardiovascular research. PMID- 27553649 TI - Aurantibacter crassamenti gen. nov., sp. nov., a bacterium isolated from marine sediment. AB - A Gram-stain-negative, strictly aerobic, orange-colored, rod-shaped, chemoheterotrophic bacterium, designated HG732T, was isolated from marine sediment in Japan. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the novel marine strain was affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes and that it shared the highest (94.1 %) sequence similarity with Kriegella aquimaris KMM 3665T. The strain could be differentiated phenotypically from related members of the family Flavobacteriaceae. Major fatty acids of strain HG732T were iso-C15:1 G, iso-C15:0 and iso-C17:0 3-OH. The polar lipid profile consisted of phosphatidylglycerol, three unidentidied aminolipids and two unidentified lipids. The DNA G+C content of the strain was determined to be 35.2 mol%, and the major respiratory quinone was identified as menaquinone 6 (MK-6). From the distinct phylogenetic position and combination of genotypic and phenotypic characteristics, the strain is considered to represent a novel genus in the family Flavobacteriaceae, for which the name Aurantibacter crassamenti gen. nov., sp. nov. is proposed. The type strain of A. crassamenti gen. nov., sp. nov. is HG732T (= KCTC 52207T = NBRC 112211T). PMID- 27553650 TI - Effects of medium-chain fatty acids on the structure and immune response of IPEC J2 cells. AB - Medium-chain fatty acids (MCFAs) have been suggested as an alternative to the use of antibiotics in animal nutrition with promising results. First, we studied the sensitivity of Salmonella Enteritidis and an enteropathogenic Escherichia coli strain against caprylic (C8), capric (C10) and lauric (C12) acids. A porcine in vitro model using the porcine cell line IPEC-J2 was used to test the effects of MCFAs on structural and immunological traits without and with a concomitant challenge with E. coli or S. Enteritidis. The three MCFAs exerted an inhibitory effect on bacterial growth, stronger for C12 than C8 or C10, S. Enteritidis being more sensitive than the E. coli strain. Flow cytometry showed a numeric concentration dependent increase in the adhesion of E. coli or S. Enteritidis to IPEC-J2 cells. Measurement of transepithelial electrical resistance after bacterial challenge showed negative effects of all MCFAs on IPEC-J2 cells at the highest concentrations. Immune parameters were affected by C8, since a concentration dependent effect starting at 5 mM was observed for mRNA expression of IL-6 and TLR-4 (up-regulated) and IL-8 (down-regulated). TLR-4 was up regulated with C10 at 2 and 5 mM. The three MCFAs affected also the epithelial morphology through down-regulation of Occludin and up-regulation of Claudin-4 expression. In conclusion, the three MCFAs under study influenced bacterial growth rates and modified the gene expression to a different degree in the cell line IPEC-J2 but the effect on the morphological structure and response of the cells after bacterial challenge could not be assessed. Although these tests show a prior estimation of MCFAs effects in intestinal epithelium, in vivo confirmation is still needed. PMID- 27553651 TI - Osteoid osteoma of the acetabular roof: a case report. AB - BACKGROUND: An acetabular location of osteoid osteoma is rare and represents less than 1 % of cases. The purpose of this clinical case report is to highlight the unusual location of osteoid osteoma and the technical difficulty of its removal. CASE PRESENTATION: We report a case of a 17-year-old Moroccan Arab boy who presented with pain in his right hip with lameness. The diagnosis of osteoid osteoma was made by imagery and confirmed by histological examination. The treatment consisted of a complete percutaneous resection scanno-guided of the nidus. The evolution was marked by complete healing with total and definitive disappearance of symptoms after 1 year. CONCLUSIONS: Osteoid osteoma of the acetabular roof is rare. The diagnosis is now easy because of the evolution of imaging. Treatment is exclusively surgical. Complete resection guarantees the absence of recurrence. The difficulty of the surgical procedure is due to the deep localization of the osteoid osteoma and because it is endosseous, it is also dangerous due to anatomical relationships and the small size of the osteoid osteoma. PMID- 27553652 TI - Teamwork enables high level of early mobilization in critically ill patients. AB - BACKGROUND: Early mobilization in critically ill patients has been shown to prevent bed-rest-associated morbidity. Reported reasons for not mobilizing patients, thereby excluding or delaying such intervention, are diverse and comprise safety considerations for high-risk critically ill patients with multiple organ support systems. This study sought to demonstrate that early mobilization performed within the first 24 h of ICU admission proves to be feasible and well tolerated in the vast majority of critically ill patients. RESULTS: General practice data were collected for 171 consecutive admissions to our ICU over a 2-month period according to a local, standardized, early mobilization protocol. The total period covered 731 patient-days, 22 (3 %) of which met our local exclusion criteria for mobilization. Of the remaining 709 patient-days, early mobilization was achieved on 86 % of them, bed-to-chair transfer on 74 %, and at least one physical therapy session on 59 %. Median time interval from ICU admission to the first early mobilization activity was 19 h (IQR = 15-23). In patients on mechanical ventilation (51 %), accounting for 46 % of patient-days, 35 % were administered vasopressors and 11 % continuous renal replacement therapy. Within this group, bed-to-chair transfer was achieved on 68 % of patient-days and at least one early mobilization activity on 80 %. Limiting factors to start early mobilization included restricted staffing capacities, diagnostic or surgical procedures, patients' refusal, as well as severe hemodynamic instability. Hemodynamic parameters were rarely affected during mobilization, causing interruption in only 0.8 % of all activities, primarily due to reversible hypotension or arrhythmia. In general, all activities were well tolerated, while patients were able to self-regulate their active early mobilization. Patients' subjective perception of physical therapy was reported to be enjoyable. CONCLUSIONS: Mobilization within the first 24 h of ICU admission is achievable in the majority of critical ill patients, in spite of mechanical ventilation, vasopressor administration, or renal replacement therapy. PMID- 27553653 TI - The Comparative Molecular Epidemiology of GII.P7_GII.6 and GII.P7_GII.7 Norovirus Outbreaks in Victoria, Australia, 2012-2014. AB - The comparative molecular epidemiology of the related GII.P7_GII.6 and GII.P7_GII.7 noroviruses has not been examined in detail. ORF 1, ORF 2 and ORF 1/ORF 2 RT-PCR as well as sequencing and phylogeny analysis were carried out on faecal specimens from 873 gastroenteritis outbreaks in Victoria, Australia (2012 2014). There were 575 (66%) detected as positive for norovirus by means of ORF 1 RT-PCR and/or ORF 2 RT-PCR. Of these, 24 (4.2%) were GII.6 (ORF 2) outbreaks, 7 (1.2%) were GII.7 (ORF 2) outbreaks, and 1 outbreak (0.2%) involved both GII.6 (ORF 2) and GII.7 (ORF 2) noroviruses. The median age of patients identified with GII.6 (ORF 2) (84 years) was significantly different from that of patients identified with GII.7 (ORF 2) (39 years). ORF 2 GII.6 and ORF 2 GII.7 sequences were always associated with a GII.P7 ORF 1 sequence, and GII.P7 sequences fell into two clusters, with one corresponding to the GII.6 ORF 2 genotype and the other to the GII.7 ORF 2 genotype, thereby indicating that the ORF 1 has been evolving separately for the two viruses. Thus, two closely related noroviruses can have a markedly different incidence and epidemiology. PMID- 27553654 TI - Methanomicrobium antiquum sp. nov., a hydrogenotrophic methanogen isolated from deep sedimentary aquifers in a natural gas field. AB - A mesophilic, hydrogenotrophic methanogen, designated strain MobHT, was isolated from sediments derived from deep sedimentary, natural-gas-bearing aquifers in Japan. Strain MobHT utilized H2/CO2 or formate, but not ethanol, 1-propanol, 2 propanol, 2-butanol or cyclopentanol, for growth and methane production. In addition, acetate and tungsten were required for growth. Yeast extract stimulated the growth, but was not required. The cells were weakly motile with multiple flagella, presented as a curved-rod-shaped (0.8*2.0 um) and occurred singly or in pairs. Strain MobHT grew at 15-40 degrees C (optimum 35 degrees C) and at pH 5.9-7.9 (optimum pH 7.0-7.5). The sodium chloride range for growth was 0-5.8 % (optimum 2 %). The G+C content of the genomic DNA was 37.6 mol%. In the phylogenetic tree based on the 16S rRNA gene sequences, strain MobHT clustered together with Methanomicrobium mobile (95.4 % in sequence similarity), and formed a distinct clade from Methanolacinia petrolearia SEBR 4847T (95.6 %) and Methanolacinia paynteri G-2000T (95.4 %). The two species of the genus Methanolacinia utilized 2-propanol, whereas strain MobHT and Methanomicrobium mobile, the sole species of the genus Methanomicrobium, do not. Based on phenotypic and phylogenetic features, we propose a novel species for the isolate with the name, Methanomicrobiumantiquum sp. nov. The type strain is MobHT (=DSM 21220T=NBRC 104160T). PMID- 27553655 TI - Outcomes of uterine sarcoma found incidentally after uterus-preserving surgery for presumed benign disease. AB - BACKGROUND: The aims of this study were to evaluate the impact of initial uterus preserving surgery, such as myomectomy or subtotal hysterectomy, on the recurrence rates of patients with uterine sarcoma found incidentally and to investigate the role of surgical re-exploration in this disease subset. METHODS: We performed a retrospective chart review for patients who had previously undergone either total hysterectomy or subtotal hysterectomy or myomectomy at the time of initial surgery for presumed benign uterine leiomyoma and were found to have uterine sarcoma on final pathology. Survival analysis was performed comparing patients according to the type of initial surgery. RESULTS: Between 2006 and 2014, 45 patients with uterine sarcoma were identified. Myomectomy or subtotal hysterectomy was performed in 15 patients, and 30 patients underwent total hysterectomy as the initial surgery. Of the patients who underwent myomectomy or subtotal hysterectomy as the initial surgery (n = 15), 14 were re explored to complete staging. Of the patients who underwent re-exploration (n = 14), five (35.8 %) had remnant sarcoma on the remaining uterus and no patients had disseminated disease. A Kaplan-Meier curve and log-rank test showed no difference in progression-free survival (P = 0.941) between the two groups. CONCLUSION: Initial uterus-preserving surgery does not appear to be associated with an adverse impact on survival outcomes for unexpected uterine sarcoma when surgical re-exploration was performed immediately. As such, surgical re exploration may be useful for removing any remnant sarcoma. PMID- 27553656 TI - Compressed sensing real-time cine cardiovascular magnetic resonance: accurate assessment of left ventricular function in a single-breath-hold. AB - BACKGROUND: Cardiovascular cine magnetic resonance (CMR) accelerated by compressed sensing (CS) is used to assess left ventricular (LV) function. However, it is difficult for prospective CS cine CMR to capture the complete end diastolic phase, which can lead to underestimation of the end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), compared to retrospective standard cine CMR. This prospective study aimed to evaluate the diagnostic quality and accuracy of single-breath-hold full cardiac cycle CS cine CMR, acquired over two heart beats, to quantify LV volume in comparison to multi breath-hold standard cine CMR. METHODS: Eighty-one participants underwent standard segmented breath-hold cine and CS real-time cine CMR examinations to obtain a stack of eight contiguous short-axis images with same high spatial (1.7 * 1.7 mm(2)) and temporal resolution (41 ms). Two radiologists independently performed qualitative analysis of image quality (score, 1 [i.e., "nondiagnostic"] to 5 [i.e., "excellent"]) and quantitative analysis of the LV volume measurements. RESULTS: The total examination time was 113 +/- 7 s for standard cine CMR and 24 +/- 4 s for CS cine CMR (p < 0.0001). The CS cine image quality was slightly lower than standard cine (4.8 +/- 0.5 for standard vs. 4.4 +/- 0.5 for CS; p < 0.0001). However, all image quality scores for CS cine were above 4 (i.e., good). No significant differences existed between standard and CS cine MR for all quantitative LV measurements. The mean differences with 95 % confidence interval (CI), based on Bland-Altman analysis, were 1.3 mL (95 % CI, -14.6 - 17.2) for LV end-diastolic volume, 0.2 mL (95 % CI, -9.8 to10.3) for LV end systolic volume, 1.1 mL (95 % CI, -10.5 to 12.7) for LV stroke volume, 1.0 g (95 % CI, -11.2 to 13.3) for LV mass, and 0.4 % (95 % CI, -4.8 - 5.6) for LV ejection fraction. The interobserver and intraobserver variability for CS cine MR ranged from -4.8 - 1.6 % and from -7.3 - 9.3 %, respectively, with slopes of the regressions ranging 0.88-1.0 and 0.86-1.03, respectively. CONCLUSIONS: Single breath-hold full cardiac cycle CS real-time cine CMR could evaluate LV volume with excellent accuracy. It may replace multi-breath-hold standard cine CMR. PMID- 27553657 TI - Influence of applied corneal endothelium image segmentation techniques on the clinical parameters. AB - The corneal endothelium state is verified on the basis of an in vivo specular microscope image from which the shape and density of cells are exploited for data description. Due to the relatively low image quality resulting from a high magnification of the living, non-stained tissue, both manual and automatic analysis of the data is a challenging task. Although, many automatic or semi automatic solutions have already been introduced, all of them are prone to inaccuracy. This work presents a comparison of four methods (fully-automated or semi-automated) for endothelial cell segmentation, all of which represent a different approach to cell segmentation; fast robust stochastic watershed (FRSW), KH method, active contours solution (SNAKE), and TOPCON ImageNET. Moreover, an improvement framework is introduced which aims to unify precise cell border location in images pre-processed with differing techniques. Finally, the influence of the selected methods on clinical parameters is examined, both with and without the improvement framework application. The experiments revealed that although the image segmentation approaches differ, the measures calculated for clinical parameters are in high accordance when CV (coefficient of variation), and CVSL (coefficient of variation of cell sides length) are considered. Higher variation was noticed for the H (hexagonality) metric. Utilisation of the improvement framework assured better repeatability of precise endothelial cell border location between the methods while diminishing the dispersion of clinical parameter values calculated for such images. Finally, it was proven statistically that the image processing method applied for endothelial cell analysis does not influence the ability to differentiate between the images using medical parameters. PMID- 27553658 TI - Pure invasive micropapillary carcinoma of the esophagogastric junction with lymph nodes and liver metastasis. AB - Invasive micropapillary carcinoma (IMPC), an aggressive variant of adenocarcinoma, is associated with a poor prognosis. Although IMPC has been reported to occur in various organs, pure IMPC has only been reported in the breast, pancreas and colon. There are no reports of IMPC of the esophagogastric junction (EGJ). According to previous reports on gastric IMPC, IMPC occupied, at most, 90 % of the whole tumor. IMPC is reported to occur least frequently in the gastric cardia. We herein report a rare case of pure IMPC of the EGJ. A 71-year old male patient presented with epigastric distress. Gastric endoscopy demonstrated an irregularly-elevated lesion of 50 mm in diameter at the EGJ. The patient underwent proximal gastrectomy, resection of the regional lymph nodes and a punch biopsy of the liver. A histopathological examination revealed that almost all of the regions, including the lymph nodes and the sites of liver metastasis, contained IMPC and that a minute region (<1 % of the whole cancer) contained tubular or papillary adenocarcinoma. The further accumulation of pure IMPC cases like the present case would help to elucidate its pathogenesis. PMID- 27553659 TI - Role of vasoactive intestinal peptide in osteoarthritis. AB - Vasoactive intestinal peptide (VIP) plays important roles in many biological functions, such as, stimulation of contractility in the heart, vasodilation, promoting neuroendocrine-immune communication, lowering arterial blood pressure, and anti-inflammatory and immune-modulatory activity. Osteoarthritis (OA) is a chronic and degenerative bone disease, which is one of the most common causes of disability and most common in both sexes as people become older. Interestingly VIP can prevent chronic cartilage damage and joint remodeling. This review article provides update information on the association of VIP and OA and its treatment. Evidences suggest that VIP is down-regulated in synovial fluid of OA, and VIP down-regulation leads to increase in the production of pro-inflammatory cytokines that might contribute to the pathogenesis of OA; however contradictory reports also exist suggesting that accumulation of VIP in joints can also contribute OA. A number of studies indicated that up-regulation of VIP can counteract the action of pro-inflammatory stimuli and alleviate the pain in OA. More clinical investigations are necessary to determine the biology of VIP and its therapeutic potential in OA that might represent the future standards of care for OA. PMID- 27553660 TI - Characterization of H7N2 Avian Influenza Virus in Wild Birds and Pikas in Qinghai Tibet Plateau Area. AB - Qinghai Lake is a major migrating bird breeding site that has experienced several recent highly pathogenic avian influenza virus (HPAIV) epizootics. From 2006 to 2009 we studied Qinghai's wild birds and pikas for evidence of AIV infections. We sampled 941 healthy wild animals and isolated seventeen H7N2 viruses (eight from pikas and nine from wild birds). The H7N2 viruses were phylogenetically closely related to each other and to viruses isolated in Hong Kong in the 1970s. We determined the pathogenicity of the H7N2 viruses by infecting chickens and mice. Our results suggest that pikas might play an important role in the ecology of AIVs, acting as intermediate hosts in which viruses become more adapted to mammals. Our findings of AI infection in pikas are consistent with previous observations and raise the possibility that pikas might play a previously unrecognized role in the ecology of AIVs peridomestic aquatic environments. PMID- 27553661 TI - Tuberculosis treatment outcome and associated factors among smear-positive pulmonary tuberculosis patients in Afar, Eastern Ethiopia: a retrospective study. AB - Evaluating the outcomes of tuberculosis treatment and understanding the specific reasons for unfavorable treatment outcome are important in evaluating the effectiveness of tuberculosis control program. A retrospective study was conducted to assess tuberculosis treatment outcomes and associated factors among smear positive pulmonary tuberculosis patients in zone-one health facilities of Afar regional state, Ethiopia. A total of 380 smear positive pulmonary tuberculosis patients' registration book recorded with complete information from Jan 2011 to Dec 2013 were analyzed. Of 380 patients included in the analysis, 238 were male and 142 female with mean age of 30.7. Overall treatment outcome were 128 (33.7%) cured, 192 (50.2%) completed, 17 (4.5%) died, 1 (0.3%) treatment failure, 34 (8.9%) default and 8 (2.1%) transfer out. Treatment success rate was 81.8%. There was statistically significance association between age (p value=0.000), sex (p-value=0.018), HIV status (p-value=0.000), four week attendance (p-value=0.000), sputum follow up test (p-value=0.000), and treatment outcome year (p-value=0.000), and treatment success (p-value=0.000). Treatment success rate almost reached to the WHO targets although yet need to work a lot for fulfillment of global targets. Regular four week attendance in continuation phase and doing follow up sputum test with unsuccessful outcome for smear positive tuberculosis patient were vital. PMID- 27553662 TI - Ventricular Tachycardia: A Rare Side Effect of Voriconazole. PMID- 27553663 TI - Hybrid alpha-Fe2O3@Ni(OH)2 nanosheet composite for high-rate-performance supercapacitor electrode. AB - In this study, we report a facile fabrication of ultrathin two-dimensional (2D) nanosheet hybrid composite, alpha-Fe2O3 nanosheet@Ni(OH)2 nanosheet, by a two step hydrothermal method to achieve high specific capacitance and good stability performance at high charging/discharging rates when serving as electrode material of supercapacitors. The alpha-Fe2O3@Ni(OH)2 hybrid electrode not only has a smooth decrease of the specific capacitance with increasing current density, compared with the sharp decline of single component of Ni(OH)2 electrode, but also presents excellent rate capability with a specific capacitance of 356 F/g at a current density of 16 A/g and excellent cycling stability (a capacity retention of 93.3% after 500 cycles), which are superior to the performances of Ni(OH)2 with a lower specific capacitance of 132 F/g and a lower capacity retention of 81.8% at 16 A/g. The results indicate such hybrid structure would be promising as excellent electrode material for good performances at high current densities in the future. PMID- 27553664 TI - Single-visit endodontic treatment of mature teeth with chronic apical abscesses using mineral trioxide aggregate cement: a randomized clinical trial. AB - BACKGROUND: Mature teeth with chronic apical abscesses characterized by intermittent discharge of pus through an associated sinus tract. This communication between oral mucosa and periapical inflammation is challenging for the sealing ability of root canal obturation material. Therefore, the study aim was to compare the outcomes of endodontic treatment using mineral trioxide aggregate (MTA) cement to the conventional gutta-percha cone and root canal sealer as an obturation material in mature teeth with chronic apical abscesses. METHODS: Mature teeth with chronic apical abscesses referred to our clinic for root canal treatment between 2010 and 2012 were treated in a single visit and distributed among treatment (T) and control (C) groups using a predetermined randomization block (TCTC). After chemo-mechanical preparation, teeth in group T received MTA cement mixed in a 0.26 water to powder ratio, and teeth group C received gutta-percha and root canal sealer using the warm vertical technique. The treatment outcomes were defined as obturation length, periapical healing, resorption of extruded material, and survival rate at least 2.5 years after treatment. Three endodontists blinded to the type of obturation material documented treatment outcomes. Statistical analysis at P < 0.05 was conducted to measure difference between the groups. RESULTS: Thirty-six teeth were treated between 2010 and 2012, and 32 teeth were evaluated in 2015. Complete periapical healing was observed in 87.5 % of MTA-treated teeth and 75.0 % of gutta-percha treated teeth. Adequate obturation length was reported in 50.0 % of MTA-treated and 37.5 % of gutta-percha-treated teeth. Complete resorption of extruded material was evident in 83.3 % MTA-treated teeth and 100.0 % gutta-percha-treated teeth. The survival rate of MTA-treated teeth was 100 % at 3, and 5 years, while the survival rate of gutta-percha-treated teeth was 83.3 % at 3, and 5 years. There was no significant difference between the groups in term of periapical healing, survival rate, obturation length, or resorption of extruded material. CONCLUSIONS: The outcomes of single-visit endodontic treatment of mature teeth with chronic apical abscesses using MTA cement were better, but not statistically significant, compared to conventional treatment. TRIAL REGISTRATION: ISRCTN15285974 . Registered retrospectively 23 June 2015. PMID- 27553665 TI - Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study. AB - BACKGROUND: Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. METHODS: One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. RESULTS: Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. CONCLUSIONS: DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations. PMID- 27553666 TI - Modeling preoperative risk factors for potentially lethal morbidities using a nationwide Japanese web-based database of patients undergoing distal gastrectomy for gastric cancer. AB - BACKGROUND: Most risk models for mortality and morbidity after distal gastrectomy have been created based on relatively small retrospective studies, and a model originating from nationwide database has been lacking. This study aimed to identify preoperative risk factors that predict the postoperative morbidities closely associated with mortality in gastric cancer patients undergoing distal gastrectomy, using data from the National Clinical Database (NCD), a nationwide web-based database in Japan. METHODS: We analyzed records from the NCD for 65,906 patients who underwent distal gastrectomy in 1,986 hospitals during 2011 and 2012. Using 80 % of these patients, we identified independent preoperative predictors for morbidities closely related with mortality. These risk factors were then validated using the remaining 20 % of patients from 2011 to 2012 and the further 35,575 records from 2013. RESULTS: Operative mortality was 1.07 % and overall morbidity was 14.2 % for the development data set. We selected eight morbidities that were closely associated with postoperative mortality, and then identified between 13 and 25 independent preoperative risk factors for each of the eight morbidities. Of these, old age, female gender, and poor ADL were the factors most frequently associated with the morbidities. The C-indices for each morbidity from the 2011 to 2012 validation data set were favorable as follows: unplanned intubation (0.797), pneumonia (0.784), systemic sepsis (0.748), renal failure (0.832), cardiac events (0.728), large blood transfusions (0.700), central nervous system (CNS) events (0.779), and anastomotic leakage (0.658). Similar C-indices were obtained for each mortality using the 2013 validation data set. CONCLUSIONS: In this study, we successfully constructed an acceptable risk model using preoperative risk factors to predict eight postoperative morbidities highly associated with mortality in gastric cancer patients. This risk model could help to tailor perioperative management and improve clinical outcomes for patients who undergo distal gastrectomy. PMID- 27553667 TI - Prediction of redox-sensitive cysteines using sequential distance and other sequence-based features. AB - BACKGROUND: Reactive oxygen species can modify the structure and function of proteins and may also act as important signaling molecules in various cellular processes. Cysteine thiol groups of proteins are particularly susceptible to oxidation. Meanwhile, their reversible oxidation is of critical roles for redox regulation and signaling. Recently, several computational tools have been developed for predicting redox-sensitive cysteines; however, those methods either only focus on catalytic redox-sensitive cysteines in thiol oxidoreductases, or heavily depend on protein structural data, thus cannot be widely used. RESULTS: In this study, we analyzed various sequence-based features potentially related to cysteine redox-sensitivity, and identified three types of features for efficient computational prediction of redox-sensitive cysteines. These features are: sequential distance to the nearby cysteines, PSSM profile and predicted secondary structure of flanking residues. After further feature selection using SVM-RFE, we developed Redox-Sensitive Cysteine Predictor (RSCP), a SVM based classifier for redox-sensitive cysteine prediction using primary sequence only. Using 10-fold cross-validation on RSC758 dataset, the accuracy, sensitivity, specificity, MCC and AUC were estimated as 0.679, 0.602, 0.756, 0.362 and 0.727, respectively. When evaluated using 10-fold cross-validation with BALOSCTdb dataset which has structure information, the model achieved performance comparable to current structure-based method. Further validation using an independent dataset indicates it is robust and of relatively better accuracy for predicting redox-sensitive cysteines from non-enzyme proteins. CONCLUSIONS: In this study, we developed a sequence-based classifier for predicting redox-sensitive cysteines. The major advantage of this method is that it does not rely on protein structure data, which ensures more extensive application compared to other current implementations. Accurate prediction of redox-sensitive cysteines not only enhances our understanding about the redox sensitivity of cysteine, it may also complement the proteomics approach and facilitate further experimental investigation of important redox-sensitive cysteines. PMID- 27553668 TI - Social and environmental predictors of walking among older adults. AB - BACKGROUND: Regular physical activity (PA) is a major factor in maintaining health in aging populations. This study examines the influences of sociodemographic, health, and environmental characteristics on older adults' walking behaviors, and the role physicians can play in promoting physical activity. METHODS: Online and paper surveys (n = 272) were distributed to community-dwelling older (age >= 60) adults from a large integrated healthcare system in two counties in Central Texas. Descriptive statistics were utilized to characterize participant's walking behaviors and places. Multivariate logistic regression was employed to predict being: 1) a frequent walker (i.e., walking at least three times a week); and 2) meeting the Centers for Disease Control and Prevention (CDC) PA recommendation through walking (i.e., walking >=150 min per week), while considering sociodemographic, health, and environmental factors. RESULTS: Individuals had a median age of 69 years, were of both genders (50.37 % female), and were primarily non-Hispanic White (84.87 %). While the majority (59.55 %) walked at least three times a week, only 27.86 % walked >=150 min a week. Factors associated with a lower likelihood of being frequent walkers included experiencing poor mental health in the past month (OR = 0.345, 95 % CI = 0.185-0.645) and residing in areas with low or moderate (versus high) perceived neighborhood cohesion (OR = 0.471, 95 % CI = 0.228-0.974), while those in Census Tracts reflecting populations with a lower median age were more likely to report frequent walking behavior (OR = 1.799, 95 % CI = 1.034-3.131). Factors associated with a lower likelihood of meeting the CDC PA recommendation included being 60-69 years (versus 70 years or older) (OR = 0.538, 95 % CI = 0.290-0.997), experiencing poor mental health in the past month (OR = 0.432, 95 % CI = 0.198 0.944), and lacking social support for walking (OR = 0.383, 95 % CI = 0.154 0.957). CONCLUSION: Given the health benefits, PA promotion must be seen as a national responsibility. In particular, physicians have a major role to play in communicating the importance of PA to their older patients and making discussions about strategies for overcoming barriers to walking an integral part of their clinical encounter with these patients. PMID- 27553669 TI - De novo assembly and characterization of the floral transcriptome of an economically important tree species, Lindera glauca (Lauraceae), including the development of EST-SSR markers for population genetics. AB - Lindera glauca (Lauraceae) is an economically important East Asian forest tree characterized by a dioecy in China and apomixis in Japan. However, patterns of population genetic diversity and structure of this species remain unknown for this species due to a lack of efficient molecular markers. In this study, we employed Illumina sequencing to analyze the transcriptomes of the female and male flower buds of L. glauca. We retrieved 59,753 and 75,075 unigenes for the female and male buds, respectively. Based on sequence similarity, 44,379 (74.27 %) unigenes for the female and 45,414 (60.49 %) unigenes for the male were matched to public databases. We identified 11,127 putative differentially expressed genes between the female and male buds and 20,048 expressed sequence tag-simple sequence repeats (EST-SSRs). From 3147 primer pairs designed successfully, 120 were selected for validation of polymorphism, and 13 could reliably amplify polymorphic bands and exhibited moderate levels of genetic diversity (e.g., N A = 4.42; H E = 0.56) when surveyed across 96 individuals of altogether six L. glauca populations from China and Japan. One of the three population genetic clusters identified in China was fixed in Japan, suggesting a historical population bottleneck following island immigration. The present study has generated a wealth of transcriptome data for future functional genomic research focused on the variable reproductive system of L. glauca (dioecy, apomixis) as well as EST-SSR markers for population genetics studies and its intriguing evolutionary shift from dioecy to apomixis in the wake of island colonization. PMID- 27553670 TI - Isolation and dynamic expression of four genes involving in shikimic acid pathway in Camellia sinensis 'Baicha 1' during periodic albinism. AB - Flavonoids are the main flavor components and functional ingredients in tea, and the shikimic acid pathway is considered as one of the most important pathways in flavonoid biosynthesis, but little was known about the function of regulatory genes in the metabolism phenolic compounds in tea plant (Camellia sinensis), especially related genes in shikimic acid pathway. The dynamic changes of catechin (predominant flavonoid) contents were analyzed in this study, and four genes (CsPPT, CsDAHPS, CsSDH and CsCS) involving in shikimic acid pathway in C. sinensis albino cultivar 'Baicha 1' were cloned and characterized. The full length cDNA sequences of these genes were obtained using reverse transcription PCR and rapid amplification of cDNA ends. At the albinistic stage, the amounts of all catechins decreased to the lowest levels, when epigallocatechin gallate was the highest, whereas gallocatechin-3-O-gallate the lowest. Gene expression patterns analyzed by qRT-PCR showed that CsPPT and CsDAHPS were highly expressed in flowers and buds, while CsSDH and CsCS showed high expression levels in buds and leaves. It was also found that the transcript abundance of shikimic acid biosynthetic genes followed a tightly regulated biphasic pattern, and was affected by albinism. The transcript levels of CsPPT and CsDAHPS were decreased at albinistic stage followed elevated expression, whereas CsSDH and CsCS were increased only at re-greening stage. Taken together, these findings suggested that these four genes in C. sinensis may play different roles in shikimic acid biosynthesis and these genes may have divergent functions. PMID- 27553671 TI - Making infection prevention education interactive can enhance knowledge and improve outcomes: Results from the Targeted Infection Prevention (TIP) Study. AB - BACKGROUND: The purpose of this study was to assess effectiveness of an interactive educational program in increasing knowledge of key infection prevention and control (IPC) principles with emphasis on indwelling device care, hand hygiene, and multidrug-resistant organisms (MDROs) among nursing home (NH) health care personnel (HCP). METHODS: We conducted a multimodal randomized controlled study involving HCP at 12 NHs. Ten comprehensive and interactive modules covered common IPC topics. We compared intervention and control scores to assess differences in pretest scores as a result of field interventions, pre- and post-test scores to assess knowledge gain, and magnitude of knowledge gain based on job categories. RESULTS: We conducted over 200 in-services across 10 topics at six intervention sites over 36 months. There were 4,962 tests returned over the course of the study, ranging from 389-633 per module. Participants were mostly female certified nursing assistants (CNAs). Score improvement was highest for modules emphasizing hand hygiene, urinary catheter care, and MDROs (15.6%, 15.9%, and 22.0%, respectively). After adjusting for cluster study design, knowledge scores were significantly higher after each educational module, suggesting the education delivery method was effective. When compared with CNAs, nursing and rehabilitation personnel scored significantly higher in their knowledge tests. CONCLUSIONS: Our intervention significantly improved IPC knowledge in HCP, especially for those involved in direct patient care. This increase in knowledge along with preemptive barrier precautions and active surveillance has enhanced resident safety by reducing MDROs and infections in high-risk NH residents. PMID- 27553672 TI - Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring. AB - Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. PMID- 27553673 TI - Immunohistochemistry of aberrant neuronal development induced by 6-propyl-2 thiouracil in rats. AB - 6-Propyl-2-thiouracil (PTU)-induced hypothyroidism disrupts neuronal/glial development. This study sought to identify the sensitive immunohistochemical parameters of developmental neurotoxicity (DNT) following PTU-exposure, as well as their responses in a 28-day toxicity study in adults. In the developmental exposure study, pregnant rats were treated with 0, 1, 3, and 10ppm PTU in drinking water from gestational day 6 to postnatal day (PND) 21 and pups were examined on PNDs 21 and 77. In the adult-stage exposure study, 5-week-old male rats were treated with 0, 0.1 and 10mg PTU/kg by oral gavage for 28 days. In the developmental exposure study on PND 21, there were fewer GFAP+, PAX6+, and DCX+ cells in the subgranular zone (SGZ) of the hippocampal dentate gyrus at >=3 or 10ppm. Regarding synaptic plasticity-related molecules, there were fewer EPHA4+ and ARC+ cells in the dentate granule cell layer. Regarding GABAergic interneuron subpopulations, there were more RELN+, CALB2+, and SST+ cells and fewer PVALB+ cells in the dentate hilus. There were also differences in the numbers of RELN+, PVALB+, CALB2+, and NPY+ cells in the cerebral cortex, and RELN+, PVALB+, and SST+ cells in the cerebellar cortex. Most of these changes were sustained until PND 77. Following adult-stage exposure (10mg/kg), there were fewer SGZ DCX+ cells, but more RELN+ and SST+ cells in the dentate hilus. Results suggest that GABAergic interneuron populations in cortical tissues, hippocampal neurogenesis, and synaptic plasticity are sensitive to PTU-induced DNT during development. In contrast, only hippocampal neurogenesis was sensitive to adult-stage exposure. PMID- 27553674 TI - PPAR-gamma activation attenuates deltamethrin-induced apoptosis by regulating cytosolic PINK1 and inhibiting mitochondrial dysfunction. AB - Central events in the mitochondrial-dependent cell death pathway include the disruption of mitochondrial membrane potential, which causes the release of apoptogenic molecules leading to cell death. Based on the cytotoxic mechanism of deltamethrin (DLM), we examined the neuroprotective mechanisms of rosiglitazone (RGZ), which is against DLM-induced neuronal cell death. In this study, we found that DLM induces apoptosis in SH-SY5Y cells as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, neuronal cell death in response to DLM was due to mitochondrial dependent-apoptosis pathways since DLM increased cytochrome c release into the cytosol and activated caspase-9. DLM exposure reduced PINK1 expression, and pretreatment with RGZ significantly reduced cytochrome c release and caspase-9 activation. RGZ also attenuated the reduction of complex I activity, mitochondrial membrane potential, and ATP levels. Pretreatment with RGZ significantly enhanced PINK1 expression in DLM-exposed cells. In addition, RGZ increased cytosolic PINK1 by inhibiting mitochondrial translocation of PINK1. Interestingly, RGZ fails to rescue DLM-induced mitochondrial dysfunction both in PINK1 knockdown and PPAR-gamma antagonist treated cells. Results from this study suggest that RGZ exerts anti-apoptotic effects against DLM-induced cytotoxicity by attenuation of mitochondrial dysfunction through cytosolic PINK1-dependent signaling pathways. PMID- 27553675 TI - Evaluation of route-to-route extrapolation factors based on assessment of repeated dose toxicity studies compiled in the database RepDose(r). AB - The majority of repeated dose toxicity studies are available for the oral route. For risk assessment, however, data are needed from the relevant exposure route, i.e. inhalation or dermal. Instead of conducting additional animal studies, route to-route (R2R) extrapolation may be performed. To explore uncertainties associated with this approach, we derived extrapolation factors (EF) based on no/lowest effect levels (NOELs/LOELs) in the Fraunhofer RepDose(r) database. For R2R extrapolation oral-to-inhalation 246 study pairs on 110 chemicals were analyzed. Systemic effects triggered the LOELs in the underlying inhalation studies in 49.2%, local effects in 21.9% and both local and systemic effects in 30.9% of the data pairs. For systemic effects in inhalation studies an EF of 2.2 (95% confidence interval: 1.2-3.1) was derived, for local effects, the EF was 4.4 (95% confidence interval: 2.0-8.6), and the EF without distinguishing local or systemic effects (any EF) was 3.2 (95%, confidence interval: 1.7-5.0). Calculation with LOELs instead of NOELs, exposure duration and intrinsic properties of the chemical (toxicity or physicochemical properties) did not influence the EF significantly. For R2R extrapolation oral-to-dermal 46 study pairs on 28 chemicals were analyzed. An overall EF of 0.4 (95%, confidence interval: 0.2-0.9) was obtained. Here, we found a significant difference of EFs for low and high toxic chemicals. Overall, we conclude that reliable systemic NOELs/LOELs can be obtained for inhalation studies via R2R extrapolation from oral studies. Based on the data for any EF we propose to use an EF of 3, which covers also the uncertainty that unexpected local effects may occur in an inhalation study. For the dermal route, our dataset was too small to allow general conclusions, but the results so far do suggest that the current ECHA guidance is conservative when assuming that dermal absorption is as high as oral absorption. PMID- 27553677 TI - The novel c-Met inhibitor capmatinib mitigates diethylnitrosamine acute liver injury in mice. AB - The receptor tyrosine kinase mesenchymal-epithelial transition factor (c-Met) sits at the interface between controlled cellular division of organogenesis and uncontrolled cellular division of carcinogenesis. c-Met contribution to the initial phases of liver injury and inflammation is still not resolved. Herein, we investigated the selective pharmacological intervention of c-Met by capmatinib (formerly known as INC280) in the diethylnitrosamine (DEN) acute liver injury model in mice. c-Met inhibition by capmatinib reduced DEN-induced elevation of the pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-17A, IL-23(p19/40) and IFN gamma, which correlated well with serum markers of hepatocellular injury (ALT, AST and LDH). The protective effects possessed by capmatinib were mainly mediated by inhibiting inflammatory cells infiltration to the liver. However, hematoxylin eosin and bax-immunohistochemical stainings revealed that capmatinib (at a dose of 10, but not 5mg/kg) aggravated DEN-induced hepatocellular ballooning and apoptosis, respectively. These effects were concordant with hepatocellular overexpression of the amino acid transporter CD98. Such capmatinib effects arised mostly from exaggerating the elevation of the mutagenic lipid peroxide 4-HNE along with MDA that enhanced DEN-induced compensatory proliferation evidenced by PCNA expression. In conclusion, inhibition of c-Met activation by capmatinib may provide protection against liver injury, but may trigger undesirable elevation of the mutagenic 4-HNE. PMID- 27553676 TI - Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4+ T cells. AB - CD4+ T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4+ T cells, and demonstrate seemingly non-monotonic alterations in IFN-gamma production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naive CD4+ T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-gamma protein production was observed in effector/memory CD4+ T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naive CD4+ T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naive, CD4+ T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naive CD4+ T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4+ T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene. PMID- 27553678 TI - Lack of differences in the regional variation of oxygen saturation in larger retinal vessels in diabetic maculopathy and proliferative diabetic retinopathy. AB - BACKGROUND: Diabetic retinopathy is characterised by morphological lesions in the ocular fundus related to disturbances in retinal blood flow. The two vision threatening forms of retinopathy show specific patterns of distribution of retinal lesions with proliferative diabetic retinopathy (PDR) developing secondary to ischaemia and hypoxia in the retinal periphery and diabetic maculopathy (DM) developing secondary to hyperperfusion and increased vascular permeability in the macular area. These differences in the distribution of retinal lesions might be reflected in regional differences in oxygen saturation in the larger retinal vessels. METHODS: Dual-wavelength retinal oximetry was performed in 30 normal persons, 30 patients with DM and 30 patients with PDR, and the oxygen saturation was measured in peripapillary vessels supplying the four retinal quadrants and in branches from the upper temporal arcades supplying, respectively, the macular area and the retinal periphery. RESULTS: The overall oxygen saturation was significantly higher in diabetic patients than in normal persons and the arteriovenous (AV) saturation difference significantly lower in the patients with DM. The regional variation in oxygen saturation was similar in the three studied groups with a decreasing saturation from the upper nasal through the lower nasal, lower temporal and the upper temporal peripapillary vessels, and with a significantly higher oxygen saturation in venules draining the macular area than in venules draining the retinal periphery. CONCLUSIONS: The regional differences in retinal lesions in vision threatening diabetic retinopathy are not reflected in regional differences in the oxygen saturation of larger retinal vessels. The development of vision threatening diabetic retinopathy depends on other factors, such as, for example, regional differences in the retinal microcirculation. PMID- 27553679 TI - High Frequency of Bone Marrow Involvement in Intravascular Large B-Cell Lymphoma. AB - Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B cell lymphoma. Thirteen cases of IVLBCL with a median age of 56 years were analyzed retrospectively. Nonspecific symptoms such as fever and hepatosplenomegaly were the most common manifestations, and the bone marrow was usually involved in 8/13 (61.5%) cases. All tumors expressed CD20, and 12/13 (92.3%) of the tumors exhibited a nongerminal center phenotype by Hans algorithm. CD5 was expressed in 3/12 (25%) of the tumors. MYC was negative in all cases, and BCL2 was positive in 10/12 (83.3%) cases. Cytogenetic analysis revealed 5 cases that did not have rearrangements in either the MYC or the BCL2 gene. No association with Epstein-Barr virus was found. Seven of 11 patients received chemotherapy. The median survival time was 6 months. Patients with hemophagocytic syndrome had poor prognoses. Our study demonstrates that IVLBCL has a poor clinical outcome with a high frequency of bone marrow involvement and that the MYC gene may not play an important role in the poor prognosis of IVLBCL. PMID- 27553680 TI - Cytological Features of Palisaded Mammary-Type Myofibroblastoma. AB - Palisaded mammary-type myofibroblastoma is a rare variant of benign stromal spindle cell tumor whose histological features are well known. Nevertheless, no cytological features have been reported to date. In this article, we describe the cytological features of a case of palisaded mammary-type myofibroblastoma in which a preoperative fine needle aspirate was obtained. Smears were moderately cellular, characterized by clusters of spindle cells, disposed in a parallel fashion and immersed in myxoid background. Although the lesion is rare, it is worth distinguishing from benign and malignant spindle cell tumors. PMID- 27553682 TI - Facile Preparation of Flavinium Organocatalysts. AB - We developed a safe, simple, inexpensive, and environmentally benign method for preparing N(5)-ethylated flavinium organocatalysts without using hazardous reagents or inert conditions as previously required. 5-Ethyl-3 methyllumiflavinium cation was prepared from its reduced form by NaNO2 -free aerobic oxidation, which was subsequently extracted onto commercial cation exchange resins under NaClO4 -free conditions. The resulting resin-immobilized flavinium salts were found to be effective organocatalysts for aerobic oxidation reactions. PMID- 27553683 TI - Morphology and spelling in French students with dyslexia: the case of silent final letters. AB - Spelling is a challenge for individuals with dyslexia. Phoneme-to-grapheme correspondence rules are highly inconsistent in French, which make them very difficult to master, in particular for dyslexics. One recurrent manifestation of this inconsistency is the presence of silent letters at the end of words. Many of these silent letters perform a morphological function. The current study examined whether students with dyslexia (aged between 10 and 15 years) benefit from the morphological status of silent final letters when spelling. We compared, their ability to spell words with silent final letters that are either morphologically justified (e.g., tricot, "knit," where the final "t" is pronounced in morphologically related words such as tricoter, "to knit" and tricoteur "knitter") or not morphologically justified (e.g., effort, "effort") to that of a group of younger children matched for reading and spelling level. Results indicated that the dyslexic students' spelling of silent final letters was impaired in comparison to the control group. Interestingly, morphological status helped the dyslexics improve the accuracy of their choice of final letters, contrary to the control group. This finding provides new evidence of morphological processing in dyslexia during spelling. PMID- 27553681 TI - Hydraulic constraints modify optimal photosynthetic profiles in giant sequoia trees. AB - Optimality theory states that whole-tree carbon gain is maximized when leaf N and photosynthetic capacity profiles are distributed along vertical light gradients such that the marginal gain of nitrogen investment is identical among leaves. However, observed photosynthetic N gradients in trees do not follow this prediction, and the causes for this apparent discrepancy remain uncertain. Our objective was to evaluate how hydraulic limitations potentially modify crown level optimization in Sequoiadendron giganteum (giant sequoia) trees up to 90 m tall. Leaf water potential (Psi l ) and branch sap flow closely followed diurnal patterns of solar radiation throughout each tree crown. Minimum leaf water potential correlated negatively with height above ground, while leaf mass per area (LMA), shoot mass per area (SMA), leaf nitrogen content (%N), and bulk leaf stable carbon isotope ratios (delta(13)C) correlated positively with height. We found no significant vertical trends in maximum leaf photosynthesis (A), stomatal conductance (g s), and intrinsic water-use efficiency (A/g s), nor in branch averaged transpiration (E L), stomatal conductance (G S), and hydraulic conductance (K L). Adjustments in hydraulic architecture appear to partially compensate for increasing hydraulic limitations with height in giant sequoia, allowing them to sustain global maximum summer water use rates exceeding 2000 kg day(-1). However, we found that leaf N and photosynthetic capacity do not follow the vertical light gradient, supporting the hypothesis that increasing limitations on water transport capacity with height modify photosynthetic optimization in tall trees. PMID- 27553684 TI - Influence of Studies Published by the Journal of the American Geriatrics Society: Top 20 Articles from 2000-2015. PMID- 27553685 TI - Low Voltage Electrowetting on Ferroelectric PVDF-HFP Insulator with Highly Tunable Contact Angle Range. AB - We demonstrate a consistent electrowetting response on ferroelectric poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) insulator covered with a thin Teflon AF layer. This bilayer exhibits a factor of 3 enhancement in the contact angle modulation compared to that of conventional single-layered Teflon AF dielectric. On the basis of the proposed model the enhancement is attributed to the high value of effective dielectric constant (epsiloneff ~ 6) of the bilayer. Furthermore, the bilayer dielectric exhibits a hysteresis-free contact angle modulation over many AC voltage cycles. But the contact angle modulation for DC voltage shows a hysteresis because of the field-induced residual polarization in the ferroelectric layer. Finally, we show that a thin bilayer exhibits contact angle modulation of Deltatheta (U) ~ 60 degrees at merely 15 V amplitude of AC voltage indicating a potential dielectric for practical low voltage electrowetting applications. A proof of concept confirms electrowetting based rapid mixing of a fluorescent dye in aqueous glycerol solution for 15 V AC signal. PMID- 27553686 TI - George V. Hillyer (1943-2015). PMID- 27553687 TI - Vitamin D advice seems at odds with new methods. PMID- 27553689 TI - Erratum to: Bone density in proton pump inhibitors users: a prospective study. PMID- 27553688 TI - Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy. AB - Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser microdissected glomeruli were used for expression profiling of 762 miRNAs by low density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs. PMID- 27553694 TI - Prevention of the Paracentesis-Induced Circulatory Dysfunction (PICD) in Cirrhosis: Is the SPA Treatment Worthwhile? PMID- 27553695 TI - A warning sign. AB - A 64year old man presented with atypical chest pain of 6h duration. Physical examination showed tachycardia and an irregularly irregular pulse. Initial EKG showed atrial fibrillation with rapid ventricular rate. Intravenous Diltiazem was administered following which there was resolution of atrial fibrillation as well as his chest pain. Troponin T and CPK-MB were minimally elevated at 0.05ng/ml (0.0-0.03ng/ml) and 8.6ng/ml (0.0-7.0ng/ml) respectively. A repeat EKG obtained after symptom resolution showed biphasic T wave inversions in V2 and V3 which prompted an emergent coronary angiogram that revealed 90% occlusion of the proximal LAD. The immediate recognition of Wellens' pattern lead to emergent coronary revascularization and prevention of acute myocardial infarction in our patient. Clinicians should be aware of this syndrome so that prompt invasive therapy can be done to avoid evolution into MI and subsequent left ventricular dysfunction. PMID- 27553690 TI - PPP1, a plant-specific regulator of transcription controls Arabidopsis development and PIN expression. AB - Directional transport of auxin is essential for plant development, with PIN auxin transport proteins representing an integral part of the machinery that controls hormone distribution. However, unlike the rapidly emerging framework of molecular determinants regulating PIN protein abundance and subcellular localization, insights into mechanisms controlling PIN transcription are still limited. Here we describe PIN2 PROMOTER BINDING PROTEIN 1 (PPP1), an evolutionary conserved plant specific DNA binding protein that acts on transcription of PIN genes. Consistent with PPP1 DNA-binding activity, PPP1 reporter proteins are nuclear localized and analysis of PPP1 null alleles and knockdown lines indicated a function as a positive regulator of PIN expression. Furthermore, we show that ppp1 pleiotropic mutant phenotypes are partially reverted by PIN overexpression, and results are presented that underline a role of PPP1-PIN promoter interaction in PIN expression control. Collectively, our findings identify an elementary, thus far unknown, plant-specific DNA-binding protein required for post-embryonic plant development, in general, and correct expression of PIN genes, in particular. PMID- 27553696 TI - Epidemiology and outcome of candidemia in internal medicine wards: A regional study in Italy. AB - BACKGROUND: More than one-third of candidemia episodes occur in Internal Medicine Wards (IMWs) but only few studies have focused on this setting and specific data about epidemiology, clinical characteristics and risk factors for mortality are scant. OBJECTIVE: To describe epidemiology and to assess risk factors for in hospital mortality among patients with candidemia in IMWs. METHODS: Multicenter retrospective cohort study on patients with candidemia cared for in IMWs of an Italian region (Emilia Romagna) from January 2012 to December 2013. Non survivors were compared with survivors; variables with p<=0.1 at univariate analysis were entered into a multivariate Cox regression model. RESULTS: 232 patients were included. Overall candidemia incidence was 2.2 cases/1000 admissions. Candida albicans accounted for 59% of cases. Antifungal treatment was started <24h, 24 72h, and >72h from blood cultures in 47%, 27% and 12% of patients, respectively; 13.8% of patients received no antifungal treatment. In-hospital mortality was 40%. At multivariate analysis, chronic-obstructive-pulmonary-disease (HR 2.72, 95%CI 1.66-4.45, p<0.001) and isolation of C. tropicalis (HR 2.18, 95%CI 1.19 3.99, p=0.01) were the independent risk factors for in-hospital mortality; central-venous-catheter removal (HR 0.59, 95%CI 0.36-0.96, p=0.03) and adequate and timely (within 72h from blood drawing) empirical therapy (HR 0.42, 95%CI 0.25 0.69, p=0.001) were protective factors. CONCLUSIONS: The present study conducted in a relatively large geographic area confirms high incidence and mortality of candidemia in IMWs, with a worrisome rate of inappropriateness in patient management. Specific interventions aimed to increase awareness of IMWs about candidemia are needed. PMID- 27553697 TI - Serum lipoprotein(a) level as long-term predictor of cardiovascular mortality in a large sample of subjects in primary cardiovascular prevention: data from the Brisighella Heart Study. AB - BACKGROUND: High lipoprotein(a) [Lp(a)] levels have been re-evaluated as an independent risk factor for atherosclerotic vascular diseases. METHODS: We assessed whether serum Lp(a) levels can significantly influence long-term survival in subjects with an equal general cardiovascular (CV) risk profile. We prospectively evaluated a sample of 1215 adult subjects from the Brisighella Heart Study cohort (M: 608; F: 607; aged 40-69) who had no cardiovascular disease at enrolment. According to the CUORE project risk-charts (Italian-specific risk charts), individuals were stratified into a low-(n=865), an intermediate-(n=275) and a high-(n=75) cardiovascular risk groups. Kaplan-Meier 25-year survival analysis was carried out examining apart each class of risk and the log-rank statistic was used to estimate, when statistically possible, the survival time of the subjects stratified into quartiles of Lp(a). RESULTS: Subjects at high and intermediate CV risk aged 56-69years (regardless of gender) and women aged 40 55years with a low CV risk profile who had lower Lp(a) levels showed a significant benefit on CV mortality (P<0.05 always) and, indicatively, on the estimated survival time (even P<0.05). The ROC curves constructing for each CV risk group using Lp(a) as test-variable and death as state-variable identified serum Lp(a) as an independent long-term CV mortality prognosticator for subjects at high CV risk (AUC=0.63, 95%CI [0.50-0.76], P=0.049) and women with an intermediate CV risk profile (AUC=0.7, 95%CI [0.52-0.79], P=0.034). CONCLUSIONS: In the light of our finding and at the best of the previous knowledge, dosing Lp(a) is confirmed as important in subjects at high or medium risk (even if in primary prevention for CV diseases), especially in women. PMID- 27553698 TI - A young woman with oligomenorrohea and dysphagia. AB - A 35-year-old house wife attended our clinic with oligomenorrhea for the last three months. She also complained of diffuse body ache, joint pain and decreased bowel movements. Very often she experienced choking sensation in the throat and had difficulty in swallowing solid food. On examination, goitre was absent but a globular pink colour mass was detected at the base of the tongue. PMID- 27553700 TI - Photoisomerization Mechanism of Ruthenium Sulfoxide Complexes: Role of the Metal Centered Excited State in the Bond Rupture and Bond Construction Processes. AB - Phototriggered intramolecular isomerization in a series of ruthenium sulfoxide complexes, [Ru(L)(tpy)(DMSO)](n+) (where tpy=2,2':6',2''-terpyridine; DMSO=dimethyl sulfoxide; L=2,2'-bipyridine (bpy), n=2; N,N,N',N' tetramethylethylenediamine (tmen) n=2; picolinate (pic), n=1; acetylacetonate (acac), n=1; oxalate (ox), n=0; malonate (mal), n=0), was investigated theoretically. It is observed that the metal-centered ligand field ((3) MC) state plays an important role in the excited state S->O isomerization of the coordinated DMSO ligand. If the population of (3) MCS state is thermally accessible and no (3) MCO can be populated from this state, photoisomerization will be turned off because the (3) MCS excited state is expected to lead to fast radiationless decay back to the original (1) GSS ground state or photodecomposition along the Ru(2+) -S stretching coordinate. On the contrary, if the population of (3) MCS (or (3) MCO ) state is inaccessible, photoinduced S->O isomerization can proceed adiabatically on the potential energy surface of the metal-to-ligand charge transfer excited states ((3) MLCTS ->(3) MLCTO ). It is hoped that these results can provide valuable information for the excited state isomerization in photochromic d(6) transition-metal complexes, which is both experimentally and intellectually challenging as a field of study. PMID- 27553699 TI - Comparative ovarian microarray analysis of juvenile hormone-responsive genes in water flea Daphnia magna: potential targets for toxicity. AB - The freshwater zooplankton Daphnia magna has been extensively employed in chemical toxicity tests such as OECD Test Guidelines 202 and 211. Previously, it has been demonstrated that the treatment of juvenile hormones (JHs) or their analogues to female daphnids can induce male offspring production. Based on this finding, a rapid screening method for detection of chemicals with JH-activity was recently developed using adult D. magna. This screening system determines whether a chemical has JH-activity by investigating the male offspring inducibility. Although this is an efficient high-throughput short-term screening system, much remains to be discovered about JH-responsive pathways in the ovary, and whether different JH-activators act via the same mechanism. JH-responsive genes in the ovary including developing oocytes are still largely undescribed. Here, we conducted comparative microarray analyses using ovaries from Daphnia magna treated with fenoxycarb (Fx; artificial JH agonist) or methyl farnesoate (MF; a putative innate JH in daphnids) to elucidate responses to JH agonists in the ovary, including developing oocytes, at a JH-sensitive period for male sex determination. We demonstrate that induction of hemoglobin genes is a well conserved response to JH even in the ovary, and a potential adverse effect of JH agonist is suppression of vitellogenin gene expression, that might cause reduction of offspring number. This is the first report demonstrating different transcriptomics profiles from MF and an artificial JH agonist in D. magna ovary, improving understanding the tissue-specific mode-of-action of JH. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27553701 TI - Phosphodiesterase 2: anti-adrenergic friend or hypertrophic foe in heart disease? PMID- 27553702 TI - Fatigue in patients with erythema migrans. AB - Fatigue is a common symptom in patients with Lyme disease. The purpose of this study was to characterize fatigue in untreated adult patients presenting with erythema migrans. Selected variables were assessed to determine if any correlated with the presence or severity of fatigue. Fatigue was assessed on the day of the evaluation by a Visual Analogue Scale (VAS), over the past 14days by the 11-item Fatigue Severity Scale (FSS-11) and over the past 28days based on a question from the 36-item Short Form General Health Survey version 2. Fifty-one patients with erythema migrans whose mean age was 49.8years, and 33 (64.7%) of whom were male, were evaluated in this study. The 3 measures of fatigue were positively correlated with one another (P<=0.01). Twenty-six (51%) had fatigue based on a VAS score above 0. Ten (19.6%) had severe fatigue based on an FSS-11 score of >=4. The strongest correlate for higher fatigue scores was having a greater total number of symptoms. Based on the FSS-11 assessment tool, approximately 20% of early Lyme patients have severe fatigue. Having a high total number of symptoms was associated with both the presence and severity of fatigue. Because prior studies have demonstrated the presence of elevated levels of proinflammatory cytokines and other molecules in the serum of highly symptomatic patients with erythema migrans, the symptom of fatigue in early Lyme disease may be a component of what has been referred to as the acute sickness response. PMID- 27553704 TI - Seedlings' Strategy to Overcome a Soil Barrier. AB - The impact of the plant hormone ethylene on seedling development has long been recognized; however, its ecophysiological relevance is unexplored. Three recent studies demonstrate that ethylene is a critical endogenous integrator of various environmental signals including mechanical stress, light, and oxygen availability during seedling germination and growth through the soil. PMID- 27553703 TI - State-of-the-art monitoring in treatment of dengue shock syndrome: a case series. AB - BACKGROUND: Early recognition and treatment of circulatory volume loss is essential in the clinical management of dengue viral infection. We hypothesized that a novel computational algorithm, originally developed for noninvasive monitoring of blood loss in combat casualties, could: (1) indicate the central volume status of children with dengue during the early stages of "shock"; and (2) track fluid resuscitation status. METHODS: Continuous noninvasive photoplethysmographic waveforms were collected over a 5-month period from three children of Thai ethnicity with clinical suspicion of dengue. Waveform data were processed by the algorithm to calculate each child's Compensatory Reserve Index, where 1 represents supine normovolemia and 0 represents the circulatory volume at which hemodynamic decompensation occurs. Values between 1 and 0 indicate the proportion of reserve remaining before hemodynamic decompensation. RESULTS: This case report describes a 7-year-old Thai boy, another 7-year-old Thai boy, and a 9 year-old Thai boy who exhibited signs and symptoms of dengue shock syndrome; all the children had secondary dengue virus infections, documented by serology and reverse transcriptase polymerase chain reaction. The three boys experienced substantial plasma leakage demonstrated by pleural effusion index >25, ascites, and >20 % hemoconcentration. They received fluid administered intravenously; one received a blood transfusion. All three boys showed a significantly low initial Compensatory Reserve Index (>=0.20), indicating a clinical diagnosis of "near shock". Following 5 days with fluid resuscitation treatment, their Compensatory Reserve Index increased towards "normovolemia" (that is, Compensatory Reserve Index >0.75). CONCLUSIONS: The results from these cases demonstrate a new variation in the diagnostic capability to manage patients with dengue shock syndrome. The findings shed new light on a method that can avoid possible adverse effects of shock by noninvasive measurement of a patient's compensatory reserve rather than standard vital signs or invasive diagnostic methods. PMID- 27553705 TI - Corrigendum to "katG Ser315 and rpoB 81-bp hotspot region substitutions: Reliability for detection of drug-resistant strains of Mycobacterium tuberculosis" [J. Global Antimicrob. Resist. 5 (2016) 92-93]. PMID- 27553706 TI - Characterization of the efficiency of microbore liquid chromatography columns by van Deemter and kinetic plot analysis. AB - The efficiency of miniaturized liquid chromatography columns with inner diameters between 200 and 300 MUm has been investigated using a dedicated micro-liquid chromatography system. Fully porous, core-shell and monolithic commercially available stationary phases were compared applying van Deemter and kinetic plot analysis. The sub-2 MUm fully porous as well as the 2.7 MUm core-shell particle packed columns showed superior efficiency and similar values for the minimum reduced plate heights (2.56-2.69) before correction for extra-column contribution compared to normal-bore columns. Moreover, the influence of extra-column contribution was investigated to demonstrate the difference between apparent and intrinsic efficiency by replacing the column by a zero dead volume union to determine the band spreading caused by the system. It was demonstrated that 72% of the intrinsic efficiency could be reached. The results of the kinetic plot analysis indicate the superior performance of the sub-2 MUm fully porous particle packed column for ultra-fast liquid chromatography. PMID- 27553707 TI - Monosynaptic facilitation of group I afferents between brachioradialis and extensor carpi radialis in humans. AB - Spinal reflex arcs mediated by low-threshold (group I) afferents from muscle spindles and Golgi tendon organs modulate motoneuron excitabilities to coordinate smooth movements. In this study, the reflex arcs between the brachioradialis (BR) and extensor carpi radialis muscles (ECR) were examined in nine healthy human subjects using a post-stimulus time-histogram method. Electrical conditioning stimuli (ES) to the radial nerve branches innervating BR (BR nerve) and ECR (ECR nerve) with the intensity just below the motor threshold were delivered and firings of the ECR and BR motor units were recorded in 6 and 7 of the nine subjects, respectively. ES to the BR and ECR nerves induced a peak (facilitation) in 27/59 ECR and 22/68 BR motor units, respectively, in every subject. Such facilitation was never provoked by pure cutaneous stimulation. The remaining motor units received no effects by ES. The central synaptic delay of the facilitation was almost equal to that of the homonymous facilitation. These findings suggest that facilitation between BR and ECR exists in humans. Group I afferents should mediate the facilitation through a monosynaptic path in the spinal cord. PMID- 27553709 TI - Population dynamics of Anopheles nuneztovari in Colombia. AB - Anopheles nuneztovari is an important Colombian malaria vector widespread on both sides of the Andean Mountains, presenting morphological, behavioral and genetic heterogeneity throughout the country. The aim of this study was to evaluate whether the population structure and distribution of An. nuneztovari in Colombia are associated with ecological and physical barriers present in a heterogeneous landscape. Further, differences in behavior were addressed. A total of 5392 specimens of An. nuneztovari were collected. Mitochondrial and nuclear marker analyses detected subdivision among the northwest-west, northeast and east populations. For both markers, isolation by distance (~53%) and isolation by resistance (>30%) were determinants of population genetic differentiation. This suggests that physical barriers, geographical distance and ecological differences on both sides of the Andean Mountains promoted the genetic differentiation and population subdivision of An. nuneztovari in Colombia. This species showed the highest biting activity after 20:00h; indoor and outdoor preferences were found in all localities. These results indicated that the most effective interventions for controlling vector populations on both sides of the Andes need to be region specific. PMID- 27553708 TI - Stratification and therapeutic potential of PML in metastatic breast cancer. AB - Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification. PMID- 27553710 TI - Genetic variants of the MAVS, MITA and MFN2 genes are not associated with leprosy in Han Chinese from Southwest China. AB - Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), which has massive genomic decay and dependence on host metabolism. Accumulating evidence showed a crucial role of mitochondria in metabolism and innate immunity. We hypothesized that the mitochondrial-related antimicrobial/antiviral immune genes MAVS (mitochondrial antiviral signaling protein), MITA (mediator of IRF3 activation) and MFN2 (mitofusin 2) would confer a risk to leprosy. In this study, we performed a case-control study to analyze 11 tag and/or non-synonymous SNPs of the MAVS, MITA and MFN2 genes in 527 leprosy patients and 583 healthy individuals, and directly sequenced the three genes in 80 leprosy patients with a family history from Yunnan, Southwest China. We found no association between these SNPs and leprosy (including its subtypes) based on the frequencies of alleles, genotypes and haplotypes between the cases and controls. There was also no enrichment of potential pathogenic variants of the three genes in leprosy patients. Our results suggested that genetic variants of the MAVS, MITA and MFN2 genes might not affect the susceptibility to leprosy. PMID- 27553711 TI - Analyses of HTLV-1 sequences suggest interaction between ORF-I mutations and HAM/TSP outcome. AB - The region known as pX in the 3' end of the human T-cell lymphotropic virus type 1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. HTLV-1 ORF-I produces the protein p12 and its cleavage product p8. The functions of these proteins have been linked to immune evasion and viral infectivity and persistence. It is known that the HTLV-1 infection does not necessarily imply the development of pathological processes and here we evaluated whether natural mutations in HTLV-1 ORF-I can influence the proviral load and clinical manifestation of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). For that, we performed molecular characterization, datamining and phylogenetic analysis with HTLV-1 ORF-I sequences from 156 patients with negative or positive diagnosis for HAM/TSP. Our analyses demonstrated that some mutations may be associated with the outcome of HAM/TSP (C39R, L40F, P45L, S69G and R88K) or with proviral load (P34L and F61L). We further examined the presence of mutations in motifs of HBZ and observed that P45L mutation is located within the HBZ nuclear localization signal and was found more frequently between patients with HAM/TSP and high proviral load. These results indicate that some natural mutations are located in functional domains of ORF-I and suggests a potential association between these mutations and the proviral loads and development of HAM/TSP. Therefore it is necessary to conduct functional studies aimed at evaluating the impact of these mutations on the virus persistence and immune evasion. PMID- 27553712 TI - Oxytocin's inhibitory effect on food intake is stronger in obese than normal weight men. AB - BACKGROUND/OBJECTIVES: Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake, and raise the question of its potential to improve metabolic control in obesity. SUBJECTS/METHODS: We compared the effect of central nervous oxytocin administration (24 IU) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men. In double-blind, placebo controlled experiments, ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration, followed by the assessment of postprandial, reward-driven snack intake. Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sampled to determine concentrations of blood glucose and hormones. RESULTS: Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men, and led to a reduction in snack consumption in both groups, whereas energy expenditure remained generally unaffected. Hypothalamic-pituitary-adrenal axis secretion and the postprandial rise in plasma glucose were blunted by oxytocin in both groups. CONCLUSIONS: Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders. PMID- 27553714 TI - A Dynamic Ion-Atom Hybrid Trap for High-Resolution Cold-Collision Studies. AB - We present a dynamic ion-atom hybrid trap for studies of cold ion-neutral collisions and reactions with a significantly improved energy resolution compared with previous experiments. Our approach is based on pushing a cloud of laser cooled Rb atoms through a stationary Coulomb crystal of cold ions by using precisely controlled, tunable radiation pressure forces. We demonstrate the tuning of the atom kinetic energies over an interval ranging from 30 mK up to 350 mK with energy spreads as low as 24 mK, inferred from the comparison of experimental time-of-flight measurements with Monte Carlo trajectory simulations. We also demonstrate the first applications of our method to the investigation of chemical reactions. Our development opens up perspectives for accurate studies of the energy dependence of the reaction rates, the dynamics, and the reaction product ratios of the ion-neutral processes in the cold regime. It also paves the way for the realization of fully energy- and state-controlled cold-collision experiments. PMID- 27553713 TI - Oncogenic and tumor-suppressive mouse models for breast cancer engaging HER2/neu. AB - The human c-ErbB2 (HER2) gene is amplified in ~20% of human breast cancers (BCs), but the protein is overexpressed in ~30% of the cases indicating that multiple different mechanisms contribute to HER2 overexpression in tumors. It has long been used as a molecular marker of BC for subcategorization for the prediction of prognosis and determination of therapeutic strategies. In comparison to ER(+) BCs, HER2-positive BCs are more invasive, but the patients respond to monoclonal antibody therapy with trastuzumab or tyrosine kinase inhibitors at least at early stages. To understand the pathophysiology of HER2-driven carcinogenesis and test HER2-targeting therapeutic agents in vivo, numerous mouse models have been created that faithfully reproduce HER2(+) BCs in mice. They include MMTV-neu (active mutant or wild type, rat neu or HER2) models, neu promoter-driven neuNT transgenic mice, neuNT-knock-in mice at the neu locus and doxycycline-inducible neuNT-transgenic models. HER2/neu activates the Phosphatidylinositol-3 kinase-AKT NF-kappaB pathway to stimulate the mitogenic cyclin D1/Cdk4-Rb-E2F pathway. Of note, overexpression of HER2 also stimulates the cell autonomous Dmp1-Arf-p53 tumor suppressor pathway to quench oncogenic signals to prevent the emergence of cancer cells. Hence tumor development by MMTV-neu mice was dramatically accelerated in mice that lack Dmp1, Arf or p53 with invasion and metastasis. Expressions of neuNT under the endogenous promoter underwent gene amplification, closely recapitulating human HER2(+) BCs. MMTV-HER2 models have been shown to be useful to test humanized monoclonal antibodies to HER2. These mouse models will be useful for the screening of novel therapeutic agents against BCs with HER2 overexpression. PMID- 27553715 TI - Metabolic changes in Euphorbia palusrtis latex after fungal infection. AB - The variations of metabolic profile of the latex of wild-growing Euphorbia palustris was carried out using multivariate analysis of 1H NMR spectral data. One population was infected with fungi Fusarium sporotrichioides, Fusarium proliferatum and Alternaria alternata, while the other consisted of healthy plant species. The non-polar metabolites of latex extracts such as benzoyl ingenol laurate, amyrin decadienoate esters, cis-1,4-polyisoprene, and 24 methylenecycloartanol were identified using 1H and 2D NMR spectra. Principal component analysis of 1H NMR data provided a clear discrimination between the latex of infected and healthy plants. Minimum inhibitory concentration and minimum fungicidal concentration values of the latex extracts of healthy and infected plants were determined. The latex of infected plants was found to contain higher levels of benzoyl ingenol-laurate and 24-methylenecycloartanol, of which concentrations were strongly correlated with the antifungal activities of the latex. PMID- 27553716 TI - Inhibitory effects of atractylone on mast cell-mediated allergic reactions. AB - This study investigated a salutary effect of atractylone (Atr) which is an active constituent of Pyeongwee-San (KMP6) on mast cell-mediated allergic reactions. Our previous report indicated that KMP6 regulated allergic reactions. Thus, this study sought to determine the potential of Atr in vitro models, compound 48/80 stimulated rat peritoneal mast cells (RPMCs), phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated human mast cell line (HMC-1) cells, and stem cell factor (SCF)-stimulated RPMCs as well as in vivo models, IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and compound 48/80-induced ear swelling. The results showed that Atr inhibited compound 48/80-induced RPMCs degranulation, intracellular calcium level, tryptase release, and histamine release. Atr inhibited the up-regulation of p56(lck) tyrosine kinase activity by compound 48/80. And Atr reduced tryptase and histamine releases from PMA plus A23187-stimulated HMC-1 cells. In addition, Atr decreased histidine decarboxylase activity and expression in the activated HMC-1 cells. Atr inhibited SCF-induced morphological alteration and filamentous actin formation in RPMCs. Atr improved IgE-induced PCA reaction by decreasing the levels of histamine, IgE, interleukin (IL)-4, IL-5, IL-6, vascular endothelial growth factor, and IL-13 in the serum of PCA-induced mice. Furthermore, Atr mitigated compound 48/80-induced systemic anaphylaxis and ear swelling. Taken together, these results of this study indicate that Atr regulates the degranulation of mast cell, proving its potential in the treatment of mast cell mediated allergic reactions. PMID- 27553717 TI - Tricin-lignins: occurrence and quantitation of tricin in relation to phylogeny. AB - Tricin [5,7-dihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-4H-chromen-4-one], a flavone, was recently established as an authentic monomer in grass lignification that likely functions as a nucleation site. It is linked onto lignin as an aryl alkyl ether by radical coupling with monolignols or their acylated analogs. However, the level of tricin that incorporates into lignin remains unclear. Herein, three lignin characterization methods: acidolysis; thioacidolysis; and derivatization followed by reductive cleavage; were applied to quantitatively assess the amount of lignin-integrated tricin. Their efficiencies at cleaving the tricin-(4'-O-beta)-ether bonds and the degradation of tricin under the corresponding reaction conditions were evaluated. A hexadeuterated tricin analog was synthesized as an internal standard for accurate quantitation purposes. Thioacidolysis proved to be the most efficient method, liberating more than 91% of the tricin with little degradation. A survey of different seed-plant species for the occurrence and content of tricin showed that it is widely distributed in the lignin from species in the family Poaceae (order Poales). Tricin occurs at low levels in some commelinid monocotyledon families outside the Poaceae, such as the Arecaceae (the palms, order Arecales) and Bromeliaceae (Poales), and the non commelinid monocotyledon family Orchidaceae (Orchidales). One eudicotyledon was found to have tricin (Medicago sativa, Fabaceae). The content of lignin integrated tricin is much higher than the extractable tricin level in all cases. Lignins, including waste lignin streams from biomass processing, could therefore provide a large and alternative source of this valuable flavone, reducing the costs, and encouraging studies into its application beyond its current roles. PMID- 27553718 TI - Investigation of the midgut structure and ultrastructure in Cimex lectularius and Cimex pipistrelli (Hemiptera: Cimicidae). AB - Cimicidae are temporary ectoparasites, which means that they cannot obtain food continuously. Both Cimex species examined here, Cimex lectularius (Linnaeus 1758) and Cimex pipistrelli (Jenyns 1839), can feed on a non-natal host, C. lectularius from humans on bats, C. pipistrelli on humans, but never naturally. The midgut of C. lectularius and C. pipistrelli is composed of three distinct regions-the anterior midgut (AMG), which has a sack-like shape, the long tube-shaped middle midgut (MMG), and the posterior midgut (PMG). The different ultrastructures of the AMG, MMG, and PMG in both of the species examined suggest that these regions must fulfill different functions in the digestive system. Ultrastructural analysis showed that the AMG fulfills the role of storing food and synthesizing and secreting enzymes, while the MMG is the main organ for the synthesis of enzymes, secretion, and the storage of the reserve material. Additionally, both regions, the AMG and MMG, are involved in water absorption in the digestive system of both Cimex species. The PMG is the part of the midgut in which spherites accumulate. The results of our studies confirm the suggestion of former authors that the structure of the digestive tract of insects is not attributed solely to diet but to the basic adaptation of an ancestor. PMID- 27553719 TI - First Record of Euphoria lurida Fabricius (Coleoptera: Scarabaeidae) Injurious to Safflower (Carthamus tinctorius L.) (Asterales: Asteraceae) in Brazil. AB - We present the first report on Euphoria lurida (Fabricius) (Coleoptera: Scarabaeidae) infestation on safflower (Carthamus tinctorius L.), a crop of industrial and medicinal importance. Between September and October 2013-2015 in Parana State, we observed E. lurida adults feeding on safflower plants from the inception of flower head formation onwards, over an area of approximately 400 m2. Losses in the productivity of infested plants were estimated between 15 and 50%. The damage was characterized by perforations in the upper portion and at the base of the developing flower heads or open flowers, resulting in withering and abortion of the reproductive structures. PMID- 27553720 TI - Population Growth Parameters of Rose Aphid, Macrosiphum rosae (Hemiptera: Aphididae) on Different Rose Cultivars. AB - The rose aphid, Macrosiphum rosae (L.), is one of the most important pests on rose plants (Rosa spp.) with a worldwide distribution. As resistance indices, the development, survivorship, and reproduction of this aphid were evaluated on 10 rose cultivars, including Bella Vita, Cool Water, Dolce Vita, Maroussia, Orange Juice, Pinkpromise, Roulette, Tea, Valentine, and Persian Yellow in laboratory at 25 +/- 1 degrees C, 65 +/- 5% relative humidity, and photoperiod of 16:8 (L/D) h. Rose aphid successfully survived on all 10 rose cultivars, although mortality rate was higher on Tea and Bella Vita. The number of offspring per female differed significantly among the tested rose cultivars, and ranged from 9.2 on Tea to 38.7 nymphs on Orange Juice. Population growth parameters were significantly affected by rose cultivars. The longest mean generation time (T) was observed on Bella Vita (14.8 days) and Tea (14.7 days) and the shortest on Orange Juice (10.0 days). The net reproductive rate (R 0 ) ranged from 6.9 on Tea to 33.2 nymphs on Orange Juice cultivar. Correspondingly, the highest value of intrinsic rate of increase (r m ) was observed on Orange Juice (0.348 day-1) and lower values on Tea (0.131 day-1) followed by Bella Vita (0.154 day-1). Cluster analysis of all the measured parameters of rose aphid on different rose cultivars revealed that Tea and Bella Vita were relatively resistant to M. rosae. These findings could be useful in developing an integrated pest management (IPM) program for this aphid in urbanized areas and commercial rose potting. PMID- 27553721 TI - Effect of Environmental and Temporal Factors on Patterns of Rarity of Ephemeroptera in Stream of the Brazilian Cerrado. AB - Patterns of species' abundance and occurrence over time and space allow division of species into (i) common species, which are abundant, but have a low diversity, and (ii) rare species, which are far more diverse and less abundant. Understanding the relationships among these two species groups and how they are affected by environmental conditions is a major challenge for ecologists, especially considering the distinction between local environmental factors and regional factors and variations in abundance over the course of the year. In this study, we focused on the long-term relationship between the abundance of rare and common ephemeropterans and abiotic factors on local and regional scales. Our hypotheses are that common species will be affected primarily by regional environmental variables (i), whereas rare species will be influenced more by temporal variation (ii). Together, both local and regional abiotic variables, plus temporal variation, best explained the abundance of the common species, whereas temporal variation was the best predictor of rare species. Considering the theoretical aspects and the empirical evidence, we discuss the results based on the plasticity of the common species and the life cycle of the rare ones. We believe that our findings reinforce the need for the deconstruction of communities for a deeper understanding of their relationships with abiotic variables and, in particular, the specific aspects of these relationships in the context of the different guilds of the community. PMID- 27553722 TI - Morphological Traits of Two Seed-Feeding Beetle Species and the Relationship to Resource Traits. AB - Morphological traits are useful to investigate insect sex-related differences in body size and to reveal differences in resource use. It has been suggested that as the resource increases, so does the body size of organisms interacting with the resource, highlighting the crucial role of resource quality and quantity in determining the morphological traits of organisms interacting with the resource. Here, we describe morphological traits of two species of Bruchinae, Merobruchus terani (Kingsolver 1980) and Stator maculatopygus (Pic 1930), consuming seeds of Senegalia tenuifolia (Fabaceae: Mimosoideae). We evaluated the influence of monthly sample and sampling sites on tibia and femur length and biomass. In addition, we tested two predictions in which body size related to resource amount and body size related to longevity. Males of M. terani were heavier than females, whereas the two sexes of S. maculatopygus did not differ in biomass. Both species had larger body sizes in the late ripe-fruit stage. With respect to sampling sites, biomass of M. terani did not differ, whereas S. maculatopygus did differ in biomass. Merobruchus terani showed a positive relationship with seed traits, whereas S. maculatopygus showed no relationship. At the same time, fruit traits showed a negative effect on morphological traits for both beetle species. The longevity experiment, performed using only M. terani, showed an equal longevity and seed consumption rate for both sexes. Our study indicates that different species, interacting in the same system and performing similar functional behaviors, respond differently to the same resource. PMID- 27553723 TI - Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia. AB - OBJECTIVE: Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small-cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv-PPA), applying a rigorous study design to a large, homogeneous sv-PPA cohort. METHODS: Using a double-blind, sham-controlled counterbalanced cross-over design, we applied three tDCS conditions targeting the temporal poles of 12 sv-PPA patients. Efficiency was assessed by a semantic matching task orthogonally manipulating "living"/"nonliving" categories and verbal/visual modalities. Conforming to predominantly left-lateralized damage in sv-PPA and accounts of interhemispheric inhibition, we applied left hemisphere anodal-excitatory and right hemisphere cathodal-inhibitory tDCS, compared to sham stimulation. RESULTS: Prestimulation data, compared to 15 healthy controls, showed that patients had semantic disorders predominating with living categories in the verbal modality. Stimulation selectively impacted these most impaired domains: Left-excitatory and right-inhibitory tDCS improved semantic accuracy in verbal modality, and right-inhibitory tDCS improved processing speed with living categories and accuracy and processing speed in the combined verbal * living condition. INTERPRETATION: Our findings demonstrate the efficiency of tDCS in sv PPA by generating highly specific intrasemantic effects. They provide "proof of concept" for future applications of tDCS in therapeutic multiday regimes, potentially driving sustained improvement of semantic processing. Our data also support the hotly debated existence of a left temporal-pole network for verbal semantics selectively modulated through both left-excitatory and right-inhibitory brain stimulation. Ann Neurol 2016;80:693-707. PMID- 27553724 TI - Synthesis of novel C2-symmetric testosterone dimers and evaluation of antiproliferative activity on androgen-dependent and -independent prostate cancer cell lines. AB - A series of 7alpha-linked testosterone dimers were made and tested for biological activity on both androgen-dependent (LNCaP) and androgen-independent (DU-145 and PC3) prostate cancer cell lines. The synthesis proceeds through the formation of a trans-4-(17beta-acetoxy-4-androsten-3-one-7alpha-yl)-but-2-enoic acid 4-hydroxy alkyl ester intermediate of various length (7a-d) followed by the final dimerization step. The dimers showed interesting biological activity in comparison to the omega-hydroxyalkyl ester intermediates 7a-d. The most active dimer 8a (n=1) showed IC50 of 3.8, 1.4 and 1.8MUM, respectively on LNCaP, DU-145 and PC3 cancer cell lines. On these cell lines, this dimer is about 12, 70 and 47 times more powerful than cyproterone acetate (CPA) the reference antiandrogen. Furthermore, dimers 8b-d (n=2, 3, 4) were less active than 8a but showed selective activity on androgen-dependent LNCaP prostate cancer cells. This indicates possible application for the treatment of androgen-dependent prostate cancer. PMID- 27553725 TI - Evaluation of heterocyclic steroids and curcumin derivatives as anti-breast cancer agents: Studying the effect on apoptosis in MCF-7 breast cancer cells. AB - Anticancer agents consisting of hybrid molecules are used to improve effectiveness and diminish drug resistance. The current study aimed to introduce newly synthesized hetero-steroids of promising anticancer effects. Besides, the pro-apoptotic effects of new compounds were investigated extensively. Several pyrimidino-, triazolopyrimidino-, pyridazino-, and curcumin-steroid derivatives were synthesized, elucidated and confirmed using the spectral and analytical data. The synthesized hetero-steroids, compounds 9, 10, 11, 12, 13, 14, 15, 18, 20, 21, 22 and 24, were tested for their cytotoxic effects versus human breast cancer cells (MCF-7) using neutral red supravital dye uptake assay. Compound 24 (IC50=18MUM) showed more inhibitory influence on MCF-7 growth. Using QRT-PCR (Quantitative real time-polymerase chain reaction), CCND1, Survivin, BCL-2, CDC2, P21 and P53, genes expression levels were investigated. The study results disclose that compounds 4, 7, 18, 24 knocked down the expression levels of CCND1, Survivin, BCL-2 and CDC2. However, P21 and P53 were up-regulated by compounds 21, 22. This study introduced promising pro-apoptotic anticancer agents acting through the modulation of key regulators of apoptosis and cell cycle genes. PMID- 27553726 TI - New marine sterols from an algal-bearing gorgonian coral Pinnigorgia sp. AB - Four new marine sterols, (22E,24R)-ergosta-5,22-diene-3beta,11alpha-diol (1), (24S)-ergosta-5-ene-3beta,11alpha-diol (2), 5alpha,6alpha-epoxy-23 demethylgorgost-8-ene-3beta,7alpha-diol (3), and 5alpha,6alpha-epoxy-23 demethylgorgost-8(14)-ene-3beta,7alpha-diol (4), along with a known metabolite, 23-demethylgorgost-7-ene-3beta,5alpha,6beta-triol (5), were isolated from an algal-bearing gorgonian coral Pinnigorgia sp., collected off the waters of Taiwan. The structures of these sterols were elucidated on the basis of spectroscopic methods. Sterols 1-5 were tested for in vitro cytotoxicity in hepatic stellate cells (HSCs). Proliferation of HSCs plays a key role in the pathogenesis of liver fibrosis. PMID- 27553727 TI - Explorative study on the anticancer activity, selectivity and metabolic stability of related analogs of aminosteroid RM-133. AB - RM-133 is a key representative of a new family of aminosteroids reported as potent anticancer agents. Although RM-133 produced interesting results in 4 mouse xenograft cancer models when injected subcutaneously, it needs to be improved to increase its in vivo potency. Thus, to obtain an analog of RM-133 with a better drug potential, a structure-activity relationship study was conducted by synthesizing eleven RM-133-related compounds and addressing their antiproliferative activity on 3 human cancer cells (HL-60, OVCAR-3 and PANC-1) and 3 human normal cell lines (primary ovary, pancreas and renal proximal tubule) as well as their metabolic stability in human liver microsomes. When the 2beta tertiary amine of RM-133 was transformed into a salt or moved to position 3beta, the anticancer activity was lost. Modifying the orientation of the side chain of RM-133 increased anticancer activity and selectivity, but led to a drastic loss of stability. The protection of the 3alpha-hydroxyl of RM-133 by the formation of an ester or a carbamate stabilized the molecule against the phase I metabolic enzymes without affecting its anticancer activity. In comparison to RM-133, the 3 dimethylcarbamate derivative 3 is more selective for cancer cells over normal cells and is much more stable in liver microsomes. Those results support the use of a pro-drug strategy targeting the 3alpha-hydroxyl of RM-133 as an approach to improve its drug properties. The work presented will enable the development of an optimized anticancer drug of the aminosteroid family that is suitable for a future phase I clinical trial. PMID- 27553728 TI - Synthesis of 17beta-hydroxymethyl-17alpha-methyl-18-norandrosta-1,4,13-trien-3 one: A long-term metandienone metabolite. AB - The goal of this work was a good-yielding chemical synthesis of a metandienone metabolite which is of interest in doping analysis. 20betaOH-NorMD (IUPAC: 17beta hydroxymethyl-17alpha-methyl-18-norandrosta-1,4,13-triene-3-one) has been identified as a long-term urinary metabolite which can be detected and attributed to metandienone up to almost 3weeks after exposure. The chemical synthesis of its epimer 20alphaOH-NorMD has been described before, as was an enzymatic synthesis of 20betaOH-NorMD, but no chemical synthesis was published. PMID- 27553729 TI - 4alpha-Methylated steroids with cytotoxic activity from the soft coral Litophyton mollis. AB - Seven new (1-3, 5 and 8-10) and three previously reported (4, 6 and 7) 4alpha methylated steroids were isolated from the organic extract of the gorgonian Litophyton mollis. The structures and the relative configurations of the isolated natural products were determined on the basis of extensive analyses of their NMR and MS data. Metabolites 1 and 5-8 exhibited cytotoxic activity against K562 human chronic myelogenous leukemia cells with IC50 values below 10MUM, while at the same time displaying low toxicity against healthy PBMCs. PMID- 27553730 TI - Impact of pretransplant exposure to allosensitization factors generating HLA antibodies in the Luminex era. AB - AIM: To identify the frequency of exposure to sensitizing factors and evaluate the risk ascribable to each sensitizing factor generating HLAabs measured by Luminex. METHODS: This is a retrospective cohort study that included 502 transplanted patients and 51 patients on the waiting list for a deceased donor graft. Patients were divided into 4 groups according to the %PRA: 0%, 1 to 19%, 20 to 49% and >=50%. The OR attributable to each sensitizing factor or combination were calculated. RESULTS: Of the total 553 subjects, 53.5% were male, with an average age 35.42+/-12.96years. 69.1% were exposed to one or more sensitizing factors; 44.8% had %PRA class I>=1 and 38.9% had %PRA class II>=1. Independently or combined, sensitizing factors persist as a risk factor for the development of a %PRA >1%, >20% or >50%. After multivariate analysis, the three sensitizing factors remained significantly associated to HLAab development. CONCLUSIONS: In spite of using a most sensitive technique such as Luminex to measure the %PRA, a clear association persists between exposure to sensitizing factors and a high %PRA. The risk increases after exposure to more than one sensitizing factor. PMID- 27553731 TI - Airborne laser-spark for ambient desorption/ionisation. AB - A novel direct sampling ionisation scheme for ambient mass spectrometry is presented. Desorption and ionisation are achieved by a quasi-continuous laser induced plasma in air. Since there are no solid or liquid electrodes involved the ion source does not suffer from chemical interferences or fatigue originating from erosive burning or from electrode consumption. The overall plasma maintains electro-neutrality, minimising charge effects and accompanying long term drift of the charged particles trajectories. In the airborne plasma approach the ambient air not only serves as the plasma medium but at the same time also slows down the nascent ions via collisional cooling. Ionisation of the analyte molecules does not occur in the plasma itself but is induced by interaction with nascent ionic fragments, electrons and/or far ultraviolet photons in the plasma vicinity. At each individual air-spark an audible shockwave is formed, providing new reactive species, which expands concentrically and, thus, prevents direct contact of the analyte with the hot region inside the plasma itself. As a consequence the interaction volume between plasma and analyte does not exceed the threshold temperature for thermal dissociation or fragmentation. Experimentally this indirect ionisation scheme is demonstrated to be widely unspecific to the chemical nature of the analyte and to hardly result in any fragmentation of the studied molecules. A vast ensemble of different test analytes including polar and non-polar hydrocarbons, sugars, low mass active ingredients of pharmaceuticals as well as natural biomolecules in food samples directly out of their complex matrices could be shown to yield easily accessible yet meaningful spectra. Since the plasma medium is humid air, the chemical reaction mechanism of the ionisation is likely to be similar to other ambient ionisation techniques. Wir stellen hier eine neue Ionisationsmethode fur die Umgebungsionisation (ambient ionisation) vor. Sowohl die Desorption als auch die Ionisation erfolgen hierbei durch ein laserbetriebenes Luftplasma. Die Abwesenheit fester oder flussiger Elektroden hat zur Folge, dass die Methode weder unter chemischen Interferenzen noch unter Verschleibeta durch Korrosionsbrand oder abgetragenes Elektrodenmaterial leidet. Insgesamt betrachtet herrscht in dem Plasma Elektroneutralitat, wodurch Aufladungseffekte minimiert werden, die andernfalls zu einer langfristigenAderung der Flugbahnen von Ionen wahrend der Experimente fuhren kann. In dem Ansatz eine freischwebende Luftentladung bei Atmospharendruck zu verwenden agiert die Luft nicht nur als Plasmamedium sondert dient zusatzlich als Badgas fur die stobetainduzierte Kuhlung der entstehenden Ionen. Die Ionisierung der Analytmolekule erfolgt nicht unmittelbar im Plasma sondern in dessen direkter Umgebung durch Wechselwirkung mit freigesetzten ionischen Luftspezies, freien Elektronen oder Photonen im kurzwelligen ultravioletten Bereich. Jede Laserentladung erzeugt eine horbare Stobetawelle, in welcher neu produzierte reaktive Spezies freigesetzt werden, welche sich konzentrisch ausbreiten, so dass eine Diffusion der Analytmolekule ins heibetae Innere des Plasmas verhindert wird. Daraus folgt, dass im Interaktionsvolumen zwischen Plasma und Analyt der Temperaturgrenzwert fur eine thermische Dissoziation oder Fragmentierung der Molekule nicht uberschritten wird. Experimentell konnte belegt werden, dass das vorgestellte Ionisierungsschema sehr unselektiv bezuglich der chemischen Analytklasse ist und kaum Fragmentierungsprodukte beobachtet werden konnen. Messungen einer breitgefacherten Auswahl unterschiedlicher Testsubstanzen, wie beispielsweise polarer und unpolarer Kohlenwasserstoffe, Zuckern, niedermolekularer pharmazeutischer Wirkstoffe, sowie naturlicher Biomolekule in Lebensmittelproben unmittelbar aus ihren komplexen Matrizes, fuhrten zu aussagekraftigen Massenspektren. Zumal das Lasermedium feuchte Luft ist, scheint der Reaktionsmechanismus dem anderer Atmospharendruckionisierungsmethoden zuahneln. PMID- 27553732 TI - Dipolar excitation in the third stability region. AB - Dipole resonant excitation of ions creates instability bands which follow iso beta lines where beta is the characteristic exponent (stability parameter). Instability bands are exited most effectively on the fundamental frequency pi= betaOmega/2. Here pi is the angle resonance frequency of the dipolar voltage applied to x or y pair rods of the analyzer, and Omega is the angle frequency of the main drive voltage. Our goal is to study the mass peak shape in the third stability region with dipolar resonance excitation of the instability band with respect to the resonance frequency pi and the dipolar potential amplitude. Numerical integration of the ion motion equations with a given ion source emittance is used to investigate peak shapes and ion transmission. We show that it is possible to vary the resolution power at any part of the third stability region. A change of the dipolar potential phase leads to a periodical variation of the resolution with period pi.The most effective dipolar excitation in the y direction is along betay near the stability boundary. The mass peak shape is calculated also for a quadrupole with round rods. The best peak shape (small tails and high resolution) takes place for the rod set with r/r0=1.130. Dipolar excitation increases the transmission by approximately 5-10% at a given resolution. PMID- 27553733 TI - Peculiarities of data interpretation upon direct tissue analysis by Fourier transform ion cyclotron resonance mass spectrometry. AB - The importance of high-resolution mass spectrometry for the correct data interpretation of a direct tissue analysis is demonstrated with an example of its clinical application for an endometriosis study. Multivariate analysis of the data discovers lipid species differentially expressed in different tissues under investigation. High-resolution mass spectrometry allows unambiguous separation of peaks with close masses that correspond to proton and sodium adducts of phosphatidylcholines and to phosphatidylcholines differing in double bond number. PMID- 27553734 TI - Isomeric differentiation of chloroanilines by gas chromatography-mass spectrometry in combination with tosylation. AB - p-Chloroaniline is one of the banned aromatic amines in azo dyes, but it is very difficult to distinguish it from its isomers due to their identical retention time in chromatography and similar mass spectra. In this work, derivatization of the isomeric chloroanilines was carried out to yield the corresponding N-tosyl chloroanilines, which were completely separated by gas chromatography and also possessed clearly different electron ionization mass spectra. Thus, the three isomers could be differentiated and determined at the same time. Density functional theory calculation results indicated that the effect of the substituent pattern in electron ionization mass spectrometry is mainly due to the difference in the stability of the product ion (P2) at m/z 126, originating from the loss of tosyl radical from the precursor ion. PMID- 27553735 TI - Identification of the sites of 4-hydroxy-2-nonenal and neprilysin adduction using a linear trap quadrapole Velos Pro-Orbitrap Elite mass spectrometer. AB - Amyloid-betadegrading enzyme neprilysin (NEP) plays a pivotal role in eliminating Abeta The oxidized modification of NEP by 4-hydroxy-2-nonenal (HNE) may reduce the clearance of Abeta in cultured cells and Alzheimer's disease (AD) brains. The aim of this research is to study whether HNE could modify the NEP protein and identify the specific sites of HNE-NEP modification using a linear trap quadrapole (LTQ) Velos Pro-Orbitrap Elite mass spectrometer. NEP activity was determined after SH-SY5Y cells had incubated with HNE (20 MUM) for 24 hours. To identify the sites of NEP modification, samples of both native and HNE-modified NEP digested by trypsin were analyzed using a LTQ Velos Pro-Orbitrap Elite mass spectrometer. The NEP peptide sequence information from the fragment ion masses was used to search for the sites of NEP adduction. HNE-treated cells showed a 60% loss of NEP activity. NEP was covalently adducted at Lys 93, Lys 472 by HNE via Michael addition. Compared to the control group, the sites of modified peptide in NEP showed a consistent 156 Da increased in m/z, which provides sequence information and might contribute to further studies on drug design and the therapeutics of AD. PMID- 27553736 TI - Letter: A method for the chromatic aberration correction of a laser time of flight mass analyzer. AB - The new ion-optical system of the laser time-of-flight (TOF) mass spectrometer on the basis of two tandem wedge-shape reflectors has been offered and implemented. A new method of correcting chromatic aberration by the ion energy was proposed that used a wire electrode unit with adjustable potentials. This unit allows one to adjust the local TOF of the ions in a narrow energy range +/- (1-2)% within the total ion packet with an energy spread of +/- 20%. The method reduces the duration of the ion packets by up to 1.5ns, which enables us to obtain the restriction of resolution at a level not worse than R ~ 10500 for a TOF ~35 us. The aim of the project is to increase the separation of isobaric ions to improve the limit of detection of the laser TOF-MS for the analysis of high-purity samples. PMID- 27553737 TI - Letter: The formation of a M + 2 compound in the analysis of a trimethylsilyl derivative of monocarboxylic acids by gas chromatography electrospray ionization mass spectrometry. AB - The trimethylsilyl (TMS) derivative is one of the most widely utilized derivatives for analyzing polar compounds by gas chromatography. An ion two mass units higher than the protonated molecular ion was observed in analyzing TMS monocarboxylic acids by using gas chromatography electrospray ionization mass spectrometry (GC-ESI/MS). The structure of the M + 2 compound was investigated using tandem mass spectrometry and high-resolution mass spectrometry. The results suggest that one methyl group bound to the silicon atom was replaced by a hydroxyl group during the ESI process. One possible mechanism for the formation of the M + 2 compound is proposed. This observation suggests the possibility of synthesizing an organic compound by using ESI. PMID- 27553738 TI - Letter: alpha,omega,N,N-Dimethylaminoalkylamines as possible derivatization agents for the analysis of small carbonyl compounds by low energy mass spectrometry. AB - Reaction with alpha,omega-N,N-dimethylaminoalkylamines (2 dimethylaminoethylamine, 3- dimethylaminopropylamine, 4-dimethylaminobutylamine) to form Schiff bases followed by quaternization of the N,N-dimethylamino group by alkyl (deuteroalkyl) halides to generate fixed-charge fragments is suggested for the characterization of carbonyl compounds by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. As model objects, some aliphatic aldehydes and alicyclic and steroid ketones were involved in the modification. Using gas chromatography mass spectrometry, the first modification stage proved to be quantitative. Not only the MALDI conditions but also the nanostructurized target provided spectra that revealed peaks for the cationic parts of derivatives. It was shown that the use of deuterated alkyl halides allows one to prepare deuterium-labeled standards for possible quantitative analysis. PMID- 27553740 TI - In vitro ceftaroline combinations against meticillin-resistant Staphylococcus aureus. AB - We studied in vitro ceftaroline combinations against 61 meticillin-resistant Staphylococcus aureus isolates; 18 of them were also resistant to linezolid, using overlapping E-test method. Daptomycin-ceftaroline combination obtained lower fractional inhibitory concentration values, in comparison with those including vancomycin or linezolid against meticillin-resistant S. aureus (P<0.05). All meticillin- and linezolid-resistant S. aureus strains were resistant to ceftaroline; nevertheless, combinations with vancomycin or daptomycin showed higher synergy or addition rates than those with linezolid. PMID- 27553741 TI - How Can Single-Case Data Be Analyzed? Software Resources, Tutorial, and Reflections on Analysis. AB - The present article aims to present a series of software developments in the quantitative analysis of data obtained via single-case experimental designs (SCEDs), as well as the tutorial describing these developments. The tutorial focuses on software implementations based on freely available platforms such as R and aims to bring statistical advances closer to applied researchers and help them become autonomous agents in the data analysis stage of a study. The range of analyses dealt with in the tutorial is illustrated on a typical single-case dataset, relying heavily on graphical data representations. We illustrate how visual and quantitative analyses can be used jointly, giving complementary information and helping the researcher decide whether there is an intervention effect, how large it is, and whether it is practically significant. To help applied researchers in the use of the analyses, we have organized the data in the different ways required by the different analytical procedures and made these data available online. We also provide Internet links to all free software available, as well as all the main references to the analytical techniques. Finally, we suggest that appropriate and informative data analysis is likely to be a step forward in documenting and communicating results and also for increasing the scientific credibility of SCEDs. PMID- 27553743 TI - Reworking Seventeenth-Century Saltpetre. AB - In the early modern period, saltpetre was perhaps best known for its role as one of the three components of gunpowder. For natural philosophers in seventeenth century England, saltpetre also had important uses in chymistry and medicine. While some factories did successfully produce saltpetre in early modern England, the domestic industry was not on the whole a great success. Intellectuals who were keen to apply their knowledge in the real world saw this as an opportunity, and proposed a variety of new and improved methods that they claimed would produce this vital material more efficiently and in abundance. Yet their proposals remained on the page and their efforts fell flat. To understand the challenges and experiences faced by both scholars and artisan saltpetre-makers, I 'reworked' early modern methods of saltpetre-making with the Medieval Gunpowder Research Group. Reworking revealed procedural challenges and complexities that explain why, even with the best intentions, seventeenth-century natural philosophers struggled to get to grips with this important material. PMID- 27553742 TI - Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions. AB - BACKGROUND: Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology. METHODS: Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers. RESULTS: FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure. CONCLUSIONS: Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions. PMID- 27553744 TI - Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia. AB - BACKGROUND: Management of alopecia areata (AA) and androgenetic alopecia (AGA) is often challenging as patients may be resistant to currently available modalities of treatment. The use of stem cells may be a novel option for resistant cases. OBJECTIVE: To evaluate the safety and efficacy of the use of autologous bone marrow derived mononuclear cells (including stem cells) as compared to follicular stems cells for the management of resistant cases of AA and AGA. METHODS: This study included 40 patients (20 AA patients and 20 AGA patients), all patients were treated with a single session of intradermal injection of autologous stem cells (SCs) therapy. They were divided into four groups according to the applied modality [either autologous bone marrow derived mononuclear cells (bone marrow mononuclear cells [BMMCs] or autologous follicular stem cells [FSC]). RESULTS: Six months after stem cell therapy (SCT) injection, there was a significant improvement, confirmed by immunostaining and digital dermoscopy. The mean improvement in all groups was "very good". There was no significant difference between both methods in either type of alopecia. No serious adverse events were reported. CONCLUSION: Autologous BMMCs and FSC seem to be a safe tolerable and effective treatment for the management of both resistant AA and AGA. PMID- 27553745 TI - PCV13 vaccination for older adults: Another view. PMID- 27553746 TI - Response to Letter to the Editor regarding: Immunogenicity and safety of a 13 valent pneumococcal conjugate vaccine in adults 18-49 years of age, naive to 23 valent pneumococcal polysaccharide vaccine. PMID- 27553747 TI - Human papilloma virus vaccination and dysautonomia: Considerations for autoantibody evaluation and HLA typing. PMID- 27553748 TI - Response to letter to the editor. PMID- 27553749 TI - Retraction notice to "Development of live attenuated Streptococcus agalactiae as potential vaccines by selecting for resistance to sparfloxacin" [Vaccine 31 (2013) 2705-2712]. PMID- 27553750 TI - Bone Mineral Changes in Epilepsy Patients During Initial Years of Antiepileptic Drug Therapy. AB - Antiepileptic drug (AED) therapy is associated with decreased bone mineral density; however, the time course for this development is unclear. The aim of this study was to evaluate bone mineral changes during the initial years of AED therapy in AED-naive, newly diagnosed epilepsy patients compared with non-AED users. In 49 epilepsy patients newly started on AEDs and in 53 non-AED users of both genders, bone mineral density (BMD) and bone mineral content were measured using dual-energy X-ray absorptiometry at baseline (within the first year of therapy) and at least 1 yr later. Bone changes between the 2 assessments, adjusted for age, height, and weight, were calculated as the annual rate of change. The median duration of AED therapy was 3.5 mo at baseline and 27.6 mo at follow-up. No overall difference was found in mean BMD and bone mineral content measures between user and nonuser cohorts in both cross-sectional baseline and the annual rate of change (p > 0.05). However, users on carbamazepine monotherapy (n = 11) had an increased annual rate of total hip (-2.1% vs -0.8%, p = 0.020) and femoral neck BMD loss (-2.1% vs -0.6%, p = 0.032) compared to nonusers. They also had a marginally higher rate of femoral neck BMD loss (-2.1%, p = 0.049) compared with valproate (-0.1%, n = 13) and levetiracetam users (+0.6%, n = 13). During the initial years of AED treatment for epilepsy, no difference was found in bone measures between AED users as a group and nonuser cohorts. However, the data suggested that carbamazepine monotherapy was associated with increased bone loss at the hip regions, compared to users of levetiracetam or valproate and nonusers. Larger studies of longer duration are warranted to better delineate the bone effects of specific AEDs, with further consideration of the role of early dual-energy X-ray absorptiometry scanning and careful AED selection in potentially minimizing the impact on bone health in these patients. PMID- 27553751 TI - Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study. AB - PURPOSE: Patients with severe eosinophilic asthma often experience recurrent asthma exacerbations despite intensive inhaled corticosteroid therapy. In 2 previous double-blind studies (MENSA [NCT01691521] and SIRIUS [NCT01691508]), treatment with intravenous or subcutaneous mepolizumab was associated with significantly reduced annualized exacerbation rates and oral corticosteroid (OCS) requirements compared with placebo. The purpose of this study was to assess the long-term safety and efficacy of subcutaneous mepolizumab treatment in patients with severe eosinophilic asthma. METHODS: COSMOS was a 52-week, open-label extension study in patients who received mepolizumab or placebo in MENSA or SIRIUS. Patients received subcutaneous mepolizumab regardless of prior treatment allocation and continued to receive appropriate standard-of-care asthma therapy throughout. The primary objective was to assess the long-term safety of mepolizumab; end points included adverse events (AEs) and serious AEs (SAEs). Efficacy assessments included the annualized exacerbation rate and durability of response (defined as the exacerbation rate and OCS dose reduction when combined with MENSA and SIRIUS data, respectively). FINDINGS: In total, 558 (86%; previous mepolizumab: 358; previous placebo: 200) and 94 (14%; previous mepolizumab: 58, previous placebo: 36) patients experienced on-treatment AEs and SAEs, respectively. No fatal AEs were reported. Totals of 13 (2%) and 29 (4%) patients experienced systemic and local site reactions, respectively. There were no reports of mepolizumab-related anaphylaxis. Mepolizumab treatment was shown to exert a durable response, with patients who previously received mepolizumab in MENSA or SIRIUS maintaining reductions in exacerbation rate and OCS dosing throughout COSMOS. Patients who previously received placebo in MENSA or SIRIUS demonstrated improvements in these end points following treatment with mepolizumab in COSMOS. IMPLICATIONS: These data demonstrate a favorable safety profile of mepolizumab and indicate a durable and stable effect over time, supporting long-term treatment in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT01842607. PMID- 27553752 TI - Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature. AB - PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that is used to temporarily support the most critically ill of patients with respiratory and/or cardiac failure. Infection and its sequelae may be an indication for ECMO or infections may be acquired while on ECMO and are associated with a mortality >50%. Effective therapy requires optimal dosing. However, optimal dosing can be different in patients on ECMO because the ECMO circuit can alter drug pharmacokinetics. This review assessed the current literature for pharmacokinetic data and subsequent dosing recommendations for anti-infective drugs in patients on ECMO. METHODS: We searched the PubMed and Embase databases (1965 to February 2016) and included case reports, case series, or studies that provided pharmacokinetic data for anti-infective drugs including antibiotics, antifungals, and antivirals being used to treat patients of all age groups on ECMO. Pharmacokinetic parameters and dosing recommendations based on these data are presented. FINDINGS: The majority of data on this topic comes from neonatal studies of antibiotics from the 1980s and 1990s. These studies generally demonstrate a larger volume of distribution due to ECMO and therefore higher doses are needed initially. More adult data are now emerging, but with a predominance of case reports and case series without comparison with critically ill controls. The available pharmacokinetic analyses do suggest that volume of distribution and clearance are unchanged in the adult population, and therefore dosing recommendations largely remain unchanged. There is a lack of data on children older than 1 year of age. The data support the importance of therapeutic drug monitoring when available in this population of patients. IMPLICATIONS: This review found reasonably robust dosing recommendations for some drugs and scant or no data for other important anti-infectives. In order to better determine optimal dosing for patients on ECMO, a systematic approach is needed. Approaches that combine ex vivo ECMO experiments, animal studies, specialized pharmacokinetic modeling, and human clinical trials are being developed. PMID- 27553754 TI - Editorial Comment. PMID- 27553753 TI - Stochastic modeling of biochemical systems with multistep reactions using state dependent time delay. AB - To deal with the growing scale of molecular systems, sophisticated modelling techniques have been designed in recent years to reduce the complexity of mathematical models. Among them, a widely used approach is delayed reaction for simplifying multistep reactions. However, recent research results suggest that a delayed reaction with constant time delay is unable to describe multistep reactions accurately. To address this issue, we propose a novel approach using state-dependent time delay to approximate multistep reactions. We first use stochastic simulations to calculate time delay arising from multistep reactions exactly. Then we design algorithms to calculate time delay based on system dynamics precisely. To demonstrate the power of proposed method, two processes of mRNA degradation are used to investigate the function of time delay in determining system dynamics. In addition, a multistep pathway of metabolic synthesis is used to explore the potential of the proposed method to simplify multistep reactions with nonlinear reaction rates. Simulation results suggest that the state-dependent time delay is a promising and accurate approach to reduce model complexity and decrease the number of unknown parameters in the models. PMID- 27553755 TI - Welding of silver nanowire networks via flash white light and UV-C irradiation for highly conductive and reliable transparent electrodes. AB - In this work, silver nanowire inks with hydroxypropyl methylcellulose (HPMC) binders were coated on polyethylene terephthalate (PET) substrates and welded via flash white light and ultraviolet C (UV-C) irradiation to produce highly conductive transparent electrodes. The coated silver nanowire films were firmly welded and embedded into PET substrate successfully at room temperature and under ambient conditions using an in-house flash white light welding system and UV-C irradiation. The effects of light irradiation conditions (light energy, irradiation time, pulse duration, and pulse number) on the silver nanowire networks were studied and optimized. Bending fatigue tests were also conducted to characterize the reliability of the welded transparent conductive silver nanowire films. The surfaces of the welded silver nanowire films were analyzed via scanning electron microscopy (SEM), while the transmittance of the structures was measured using a spectrophotometer. From the results, a highly conductive and transparent silver nanowire film with excellent reliability could be achieved at room temperature under ambient conditions via the combined flash white light and UV-C irradiation welding process. PMID- 27553756 TI - Assessment of Napier grass accessions in lowland and highland tropical environments of East Africa: water stress indices, water use and water use efficiency. AB - BACKGROUND: Low rainfall is a major limitation to expanding the dairy industry in semi-arid environments in East Africa. In such dry areas, plants need to keep their tissues hydrated and stomata open for carbon exchange and to grow. On this basis, we assessed the productivity of 10 lines of Napier grass (Pennisetum purpureum Schum.), which formed three yield clusters: low yielding (LYC), moderate yielding (MYC), and high yielding (HYC), in a wet highland (Muguga) and semi-arid lowland (Katumani) of Kenya. Stomatal conductance (gs ), leaf water potential (LWP) and relative water content (RWC) were monitored, and water use simulated, over four growth cycles in 2012. These were used with measurements of leaf area index (LAI) and plant dry weight to explore the possible use of these physiological parameters for assessing productivity potential of Napier grass accessions. RESULTS: The plants were less stressed at Muguga, where gs was 700 1000 mmol m-2 s-1 , LWP -0.4 to -0.9 MPa and RWC was 82-95%; these values at Katumani were 450-750 mmol m-2 s-1 , -0.7 to -1.4 MPa and 74-93%, respectively. Total water use at Katumani was of the order HYC ~ MYC (390 mm) > LYC (370 mm), and water use efficiency (WUE, kg ha-1 mm-1 ) followed the same order HYC (34.3) > MYC (32.6) > LYC (24.9); whereas at Muguga water use averaged 710 mm for HYC and MYC, greater than 676 mm for LYC, and WUE (kg ha-1 mm-1 ) averaged 29.2 for HYC and MYC, and 19.4 for LYC. CONCLUSIONS: The three water stress indices were poor, whereas vigorous early canopy development (determined as LAI) was a more reliable predictor of productivity potential of Napier grasses. In these dry environments, therefore, early rapid canopy development can be an effective indicator of yield potential and a credible selection criterion. (c) 2016 Society of Chemical Industry. PMID- 27553759 TI - A Generalized Lossy Transmission-Line Model for Tunable Graphene-Based Transmission Lines with Attenuation Phenomenon. AB - To investigate the frequency shift phenomenon by inserting graphene, a generalized lossy transmission-line model and the related electrical parameter extraction theory are proposed in this paper. Three kinds of graphene-based transmission lines with attenuation phenomenon including microstrip line, double side parallel strip line, and uniplanar coplanar waveguide are analyzed under the common conditions where different chemical potentials are loaded on graphene. The values of attenuation constant and phase constant, and the real and imaginary parts of the characteristic impedance of transmission lines are extracted to analyze in details. When the attenuation constant and the reactance part of the characteristic impedance are approximately equal to zero, this kind of transmission line has low or zero insertion loss. On the contrary, the transmission line is under the radiation mode with obvious insertion loss. The phase constant changes linearly under the transmission mode and can be varied with changing of chemical potentials which attributes to the property of frequency tunability. Furthermore, a bandwidth reconfigurable uniplanar coplanar waveguide power divider is simulated to demonstrate that this theory can be applied to the design of three-port devices. In summary, this work provides a strong potential approach and design theory to help design other kinds of terahertz and mid-infrared reconfigurable devices. PMID- 27553760 TI - Dietary effect of dried bay leaves (Laurus nobilis) meal on some biochemical parameters and on plasma oxidative status in New Zealand white growing rabbit. AB - Effects of dietary supplementation of Laurus nobilis on selected biochemical parameters and plasma oxidative status in growing rabbits, fed with and without enriched-fat diet, integrated with and without dried bay leaves meal, were investigated. In the test, 120 New Zealand white 35-day-old male rabbits were divided into four homogeneous groups of 30 animals each. A negative control group (CON) received a feed that met the animal nutrient requirement; a positive control group (CG) receiving a supplement of 2.5% pig fat in feed; an experimental group (GA) feeding an integration of 2.5% pig fat and 1 g/kg of dried bay leaves (Laurus nobilis) in feed; an experimental group (CA) with dried bay leaves at the rate of 1 g/kg in feed. The dietary integration with dried bay leaves meal have resulted in a significant decrease in the blood lipid profile, glycemic profile and liver enzymes, with reduced levels of ALT and AST, glucose, total cholesterol, LDL cholesterol, triglycerides and increased HDL cholesterol. Plasma oxidative status markers have statistically improved with an increase in blood total phenols, SOD, ORAC, the FRAP and lipo-vitamin concentration, together with a significant reduction in ROMs and the MDA values. The results of present research underline that the dietary treatment with bay leaves meal, in the extend of 1 g/kg feed, confirms the lowering cholesterol activity and the epato protective and ipo-glycemic effect in enrich-fat diet, controlling the oxidative status of plasma markers. PMID- 27553758 TI - HMGB1 and thrombin mediate the blood-brain barrier dysfunction acting as biomarkers of neuroinflammation and progression to neurodegeneration in Alzheimer's disease. AB - BACKGROUND: The blood-brain barrier (BBB) dysfunction represents an early feature of Alzheimer's disease (AD) that precedes the hallmarks of amyloid beta (amyloid beta) plaque deposition and neuronal neurofibrillary tangle (NFT) formation. A damaged BBB correlates directly with neuroinflammation involving microglial activation and reactive astrogliosis, which is associated with increased expression and/or release of high-mobility group box protein 1 (HMGB1) and thrombin. However, the link between the presence of these molecules, BBB damage, and progression to neurodegeneration in AD is still elusive. Therefore, we aimed to profile and validate non-invasive clinical biomarkers of BBB dysfunction and neuroinflammation to assess the progression to neurodegeneration in mild cognitive impairment (MCI) and AD patients. METHODS: We determined the serum levels of various proinflammatory damage-associated molecules in aged control subjects and patients with MCI or AD using validated ELISA kits. We then assessed the specific and direct effects of such molecules on BBB integrity in vitro using human primary brain microvascular endothelial cells or a cell line. RESULTS: We observed a significant increase in serum HMGB1 and soluble receptor for advanced glycation end products (sRAGE) that correlated well with amyloid beta levels in AD patients (vs. control subjects). Interestingly, serum HMGB1 levels were significantly elevated in MCI patients compared to controls or AD patients. In addition, as a marker of BBB damage, soluble thrombomodulin (sTM) antigen, and activity were significantly (and distinctly) increased in MCI and AD patients. Direct in vitro BBB integrity assessment further revealed a significant and concentration-dependent increase in paracellular permeability to dextrans by HMGB1 or alpha-thrombin, possibly through disruption of zona occludins-1 bands. Pre-treatment with anti-HMGB1 monoclonal antibody blocked HMGB1 effects and leaving BBB integrity intact. CONCLUSIONS: Our current studies indicate that thrombin and HMGB1 are causal proximate proinflammatory mediators of BBB dysfunction, while sTM levels may indicate BBB endothelial damage; HMGB1 and sRAGE might serve as clinical biomarkers for progression and/or therapeutic efficacy along the AD spectrum. PMID- 27553761 TI - Dietary carbohydrates improve oxidative status of common dentex (Dentex dentex) juveniles, a carnivorous fish species. AB - Common dentex (Dentex dentex) is an appreciated carnivorous fish with high growth rate and life cycle adaptable to existing farming techniques. Since the use of carbohydrates is an economic and sustainable alternative for a protein-sparing effect, the study of how this macronutrient affects the welfare of carnivorous species must be studied. The aim of the present study was to evaluate the effects of different types and levels of carbohydrates on common dentex oxidative status. Nine isonitrogenous (43%) and isoenergetic (22MJkg-1) diets were formulated combining three types (pregelatinized starch-PS, dextrin-Dx and maltodextrin-Mx) and three levels (12, 18 and 24%) of carbohydrates. The activities of catalase CAT, superoxide dismutase-SOD, glutathione peroxidase-GPX, glutathione reductase GR and glucose 6-phosphate dehydrogenase-G6PDH, SOD isoenzymatic profile, lipid peroxidation-LPO and protein oxidation-PO were determined in liver and white muscle. SOD and CAT were not affected. GPX in liver and white muscle and GR in liver increased at higher inclusion carbohydrates levels. The lowest levels of GR and G6PDH in both tissues and LPO in liver were observed in maltodextrin groups. No significant effects by carbohydrate source were observed in liver PO and white muscle LPO. Regarding carbohydrate level effect, 18% and 24% dietary inclusion level decreased LPO in white muscle and PO in liver. LPO in liver was also decreased at 24% inclusion level. Altogether, results indicate the use of carbohydrates as an alternative energy source does not produce negative effects on oxidative status of common dentex, on the contrary, even contribute to their oxidative protection. PMID- 27553762 TI - Laparoscopy Instructional Videos: The Effect of Preoperative Compared With Intraoperative Use on Learning Curves. AB - OBJECTIVE: Previous studies have shown that the use of intraoperative instructional videos has a positive effect on learning laparoscopic procedures. This study investigated the effect of the timing of the instructional videos on learning curves in laparoscopic skills training. DESIGN: After completing a basic skills course on a virtual reality simulator, medical students and residents with less than 1 hour experience using laparoscopic instruments were randomized into 2 groups. Using an instructional video either preoperatively or intraoperatively, both groups then performed 4 repetitions of a standardized task on the TrEndo augmented reality. With the TrEndo, 9 motion analysis parameters (MAPs) were recorded for each session (4 MAPs for each hand and time). These were the primary outcome measurements for performance. The time spent watching the instructional video was also recorded. Improvement in performance was studied within and between groups. SETTING: Medical Center Leeuwarden, a secondary care hospital located in Leeuwarden, The Netherlands. PARTICIPANTS: Right-hand dominant medical student and residents with more than 1 hour experience operating any kind of laparoscopic instruments were participated. A total of 23 persons entered the study, of which 21 completed the study course. RESULTS: In both groups, at least 5 of 9 MAPs showed significant improvements between repetition 1 and 4. When both groups were compared after completion of repetition 4, no significant differences in improvement were detected. The intraoperative group showed significant improvement in 3 MAPs of the left-nondominant-hand, compared with one MAP for the preoperative group. CONCLUSION: No significant differences in learning curves could be detected between the subjects who used intraoperative instructional videos and those who used preoperative instructional videos. Intraoperative video instruction may result in improved dexterity of the nondominant hand. PMID- 27553763 TI - Visual disturbance as the presenting symptom in acute promyelocytic leukaemia. PMID- 27553764 TI - Experimental model of benign paroxysmal positional vertigo with biphasic nystagmus using isolated semicircular canals. AB - CONCLUSIONS: The co-existence of cupulolithiasis and canalolithiasis might be a possible mechanism for the spontaneous inversion of positional nystagmus. OBJECTIVE: To investigate the mechanism of spontaneous inversion of nystagmus direction without a positional change in experimental models of co-existing cupulolithiasis and canalolithiasis. METHODS: Co-existing canalolithiasis and cupulolithiasis models were prepared using the bullfrog posterior semicircular canal (PSC). Ten bullfrogs were used. The ampullary nerve discharges were recorded as compound action potentials (CAPs). First, an otoconial mass was placed on the cupula to produce cupulolithiasis. Subsequently, another otoconial mass was introduced into the canal lumen to produce canalolithiasis. Decremental time constants for cupulolithiasis and incremental time constants for canalolithiasis were determined. RESULTS: At first the CAPs increased and continued for a long time when the cupulolithiasis was generated. Subsequently the CAPs were suppressed by creating canalolithiasis. Finally, the CAPs increased again after the motion of otoconia inside the canal lumen stopped. The decremental time constant for cupulolithiasis was significantly longer than the incremental time constant for canalolithiasis. PMID- 27553765 TI - Metabolic and immunologic aspects of fetoplacental insufficiency. AB - PROBLEM: The chronic placental insufficiency is the most common cause of intrauterine hypoxia, retardation of fetal growth, and other threatening conditions. Immune disturbances may occur in the system "mother-placenta-fetus." METHOD OF STUDY: Biochemical blood indicators were studied on an automated biochemical analyzer. Pattern of lymphocyte subpopulations was detected by direct membrane immunofluorescence. RESULTS: Study revealed imbalance of immune parameters, caused by placental insufficiency (increase natural killers (CD16(+) , CD56(+) ), B lymphocytes (CD19(+) CD3(-) ), T and B lymphocytes with HLA-DR(+) antigen, and early activation of immune cells (by CD25(+) ), as well as disorders in apoptotic mechanisms (by CD95(+) )). CONCLUSION: Placental insufficiency leads to abnormalities of the immune system in pregnant, parturient women and maternity patients which were evaluated by localization of activation markers CD25(+) CD95(+) on the CD3(+) , CD4(+) , CD8(+) , CD16(+) , CD56(+) lymphocytes. This is reflected in the change of lymphocyte functions in newborns. PMID- 27553766 TI - Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC. AB - BACKGROUND AND OBJECTIVE: Serum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells. METHODS: Normal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production. We examined MUC5AC secretion from NHBE cells exposed to recombinant human (rh) periostin or IL-13 in the presence and absence of OC-20, a periostin-neutralizing antibody. RESULTS: IL-13 induced periostin protein which was predominantly secreted towards the basal surface of the cells. Periostin production was much greater from goblet cells than ciliated cells (P < 0.001). Periostin production after exposure to IL-13 was attenuated by both leflunomide (P < 0.001) and PD98059 (P < 0.001). The addition of exogenous periostin modestly increased MUC5AC secretion (P < 0.01), but did not visibly change cell morphology. IL-13-induced MUC5AC secretion was attenuated by OC-20 (P < 0.01). CONCLUSION: Periostin production in differentiated airway cells is mediated by JAK/STAT6 and MEK/ERK pathways. Periostin secretion is much greater from immunologically active goblet cells. IL-13-driven mucin production is partially inhibited by OC-20. PMID- 27553767 TI - Charge Transport and Conductance Switching of Redox-Active Azulene Derivatives. AB - Azulene (Az) is a non-alternating, aromatic hydrocarbon composed of a five membered, electron-rich and a seven-membered, electron-poor ring; an electron distribution that provides intrinsic redox activity. By varying the attachment points of the two electrode-bridging substituents to the Az center, the influence of the redox functionality on charge transport is evaluated. The conductance of the 1,3 Az derivative is at least one order of magnitude lower than those of the 2,6 Az and 4,7 Az derivatives, in agreement with density functional theory (DFT) calculations. In addition, only 1,3 Az exhibits pronounced nonlinear current voltage characteristics with hysteresis, indicating a bias-dependent conductance switching. DFT identifies the LUMO to be nearest to the Fermi energy of the electrodes, but to be an active transport channel only in the case of the 2,6 and the 4,7 Az derivatives, whereas the 1,3 Az derivative uses the HOMO at low and the LUMO+1 at high bias. In return, the localized, weakly coupled LUMO of 1,3 Az creates a slow electron-hopping channel responsible for the voltage-induced switching due to the occupation of a single molecular orbital (MO). PMID- 27553768 TI - [Not Available]. PMID- 27553769 TI - Impact of three malocclusion traits on the quality of life of orthodontic patients. AB - BACKGROUND/OBJECTIVES: Malocclusion can have a negative impact on the quality of life, affecting the individual physically and psychosocially. The aim of this study was to determine the impact of three malocclusion traits on the quality of life of the patients. METHODOLOGY: This was a clinic-based, comparative, cross sectional study involving 120 patients between 10 and 20years of age, with crowding, spacing and increased overjet. There were also 40 control subjects. The quality of life was determined using the Oral Health Impact Profile short-form (OHIP-14). RESULTS: Each of the malocclusion traits studied was found to significantly affect the oral health-related quality of life (OHRQoL) of the patients relative to the controls. Thirty-two percent of those with malocclusion had impact on their quality of life compared with three percent of those in the control group. CONCLUSION: OHQoL was poorer in patients with malocclusion and patients with increased overjet recorded the highest level of impact on their quality of life. PMID- 27553771 TI - Interaction of BDNF rs6265 variants and energy and protein intake in the risk for glucose intolerance and type 2 diabetes in middle-aged adults. AB - OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is associated with the risk for Alzheimer's disease and type 2 diabetes. The aim of this study was to examine the association of BDNF variants with type 2 diabetes and the interactions of different BDNF genotypes with dietary habits and food and nutrient intakes in middle-aged adults. METHODS: The study population included 8840 adults ages 40 to 65 y from the Ansan and Asung areas in the Korean Genome Epidemiology Study, a cross-sectional study of Korean adults, conducted from 2001 to 2002. Adjusted odd ratios for the prevalence of glucose intolerance and type 2 diabetes according to BDNF genotypes were calculated after adjusting for age, sex, residence area, body mass index, physical activity, and smoking and stress status. Nutrient intake was calculated from usual food intake determined by semiquantitative food frequencies using the nutrient assessment software. RESULTS: BDNF rs6265 Val/Met and Met/Met variants were negatively associated with the risk for type 2 diabetes after adjusting for covariates. Serum glucose levels after glucose loading and hemoglobin A1c, but not serum insulin levels, also were negatively associated with BDNF Val/Met and Met/Met. In subgroup analysis, sex and stress levels had an interaction with BDNF Val/Met in the risk for type 2 diabetes. Glucose-intolerant and diabetic, but not nondiabetic, patients with BDNF Met/Met had nominally, but significantly higher intakes of energy than those with BDNF Val/Val. BDNF rs6265 had consistent gene-diet interactions with energy and protein intake. With low energy, low-protein, and high-carbohydrate intake, BDNF Val/Met lowered the risk for type 2 diabetes after adjusting for confounding factors. BDNF Val/Met did not compensate for developing type 2 diabetes with high-energy intake. Additionally, indexes of insulin resistance and insulin secretion showed the same gene-energy interaction as type 2 diabetes. CONCLUSIONS: BDNF Val/Met and Met/Met variants (rs6265) decreases the risk for glucose intolerance and type 2 diabetes. BDNF variants interacted with nutrient intake, especially energy and protein intake: Middle-aged individuals with BDNF Val/Val are prone to developing type 2 diabetes even with low energy and protein intake. PMID- 27553772 TI - Multivitamin/mineral supplements: Rationale and safety - A systematic review. AB - Multivitamin/mineral supplements (MVM) are widely used in many populations. In particular, in pregnant women, MVM together with iron and folic acid are recommended to improve birth outcome and reduce low birth weight and rates of miscarriage. However, MVM use is common in the general population. This raises questions regarding the safety of long-term use of these supplements. To estimate the safety of MVM use, we performed a literature search for randomized, controlled studies for supplements with a combination of at least nine vitamins and three minerals at a maximum concentration of 100% of the recommended dietary allowance. We found nine studies evaluating the use and efficacy of MVM in pregnant women and healthy adults and six studies in the elderly where adverse effects were explicitly addressed. Only minor adverse effects (e.g., unspecific gastrointestinal symptoms) were reported in all studies. In particular, there were no significant differences between treatment and placebo groups. MVM use within the range of the dietary reference intake will not result in excess intake, even when including the impact of food and fortified food, and does not increase mortality. Taken together, these findings indicate that MVM can be safe for long-term use (more than 10 y). PMID- 27553773 TI - A predictive nondestructive model for the covariation of tree height, diameter, and stem volume scaling relationships. AB - Metabolic scaling theory (MST) posits that the scaling exponents among plant height H, diameter D, and biomass M will covary across phyletically diverse species. However, the relationships between scaling exponents and normalization constants remain unclear. Therefore, we developed a predictive model for the covariation of H, D, and stem volume V scaling relationships and used data from Chinese fir (Cunninghamia lanceolata) in Jiangxi province, China to test it. As predicted by the model and supported by the data, normalization constants are positively correlated with their associated scaling exponents for D vs. V and H vs. V, whereas normalization constants are negatively correlated with the scaling exponents of H vs. D. The prediction model also yielded reliable estimations of V (mean absolute percentage error = 10.5 +/- 0.32 SE across 12 model calibrated sites). These results (1) support a totally new covariation scaling model, (2) indicate that differences in stem volume scaling relationships at the intra specific level are driven by anatomical or ecophysiological responses to site quality and/or management practices, and (3) provide an accurate non-destructive method for predicting Chinese fir stem volume. PMID- 27553774 TI - Emerging role of chemokine CC motif ligand 4 related mechanisms in diabetes mellitus and cardiovascular disease: friends or foes? AB - Chemokines are critical components in pathology. The roles of chemokine CC motif ligand 4 (CCL4) and its receptor are associated with diabetes mellitus (DM) and atherosclerosis cardiovascular diseases. However, due to the complexity of these diseases, the specific effects of CCL4 remain unclear, although recent reports have suggested that multiple pathways are related to CCL4. In this review, we provide an overview of the role and potential mechanisms of CCL4 and one of its major receptors, fifth CC chemokine receptor (CCR5), in DM and cardiovascular diseases. CCL4-related mechanisms, including CCL4 and CCR5, might provide potential therapeutic targets in DM and/or atherosclerosis cardiovascular diseases. PMID- 27553775 TI - Perceived Weight Discrimination and 10-Year Risk of Allostatic Load Among US Adults. AB - BACKGROUND: Discrimination promotes multisystem physiological dysregulation termed allostatic load, which predicts morbidity and mortality. It remains unclear whether weight-related discrimination influences allostatic load. PURPOSE: The aim of this study was to prospectively examine 10-year associations between weight discrimination, allostatic load, and its components among adults 25-75 years in the Midlife Development in the US Biomarker Substudy. METHODS: Participants with information on weight discrimination were analyzed (n=986). At both timepoints, participants self-reported the frequency of perceived weight discrimination across nine scenarios as "never/rarely" (scored as 0), "sometimes" (1), or "often" (2). The two scores were averaged and then dichotomized as "experienced" versus "not experienced" discrimination. High allostatic load was defined as having >=3 out of 7 dysregulated systems (cardiovascular, sympathetic/parasympathetic nervous systems, hypothalamic pituitary axis, inflammatory, lipid/metabolic, and glucose metabolism), which collectively included 24 biomarkers. Relative risks (RR) were estimated from multivariate models adjusted for sociodemographic and health characteristics, other forms of discrimination, and BMI. RESULTS: Over 41% of the sample had obesity, and 6% reported weight discrimination at follow-up. In multivariable-adjusted analyses, individuals who experienced (versus did not experience) weight discrimination had twice the risk of high allostatic load (RR, 2.07; 95 % CI, 1.21; 3.55 for baseline discrimination; 2.16, 95 % CI, 1.39; 3.36 for long-term discrimination). Weight discrimination was associated with lipid/metabolic dysregulation (1.56; 95 % CI 1.02, 2.40), glucose metabolism (1.99; 95 % CI 1.34, 2.95), and inflammation (1.76; 95 % CI 1.22, 2.54), but no other systems. CONCLUSIONS: Perceived weight discrimination doubles the 10-year risk of high allostatic load. Eliminating weight stigma may reduce physiological dysregulation, improving obesity-related morbidity and mortality. PMID- 27553776 TI - Patients' perceptions of palliative care quality in hospice inpatient care, hospice day care, palliative units in nursing homes, and home care: a cross sectional study. AB - BACKGROUND: Patients' perceptions of care quality within and across settings are important for the further development of palliative care. The aim was to investigate patients' perceptions of palliative care quality within settings, including perceptions of care received and their subjective importance, and contrast palliative care quality across settings. METHOD: A cross-sectional study including 191 patients in late palliative phase (73 % response rate) admitted to hospice inpatient care, hospice day care, palliative units in nursing homes, and home care was conducted, using the Quality from the Patients' Perspective instrument-palliative care (QPP-PC). QPP-PC comprises four dimensions and 12 factors; "medical-technical competence" (MT) (2 factors), "physical-technical conditions" (PT) (one factor), "identity-orientation approach" (ID) (4 factors), "sociocultural atmosphere" (SC) (5 factors), and three single items (S); medical care, personal hygiene and atmosphere. Data were analysed using paired-samples t test and analysis of covariance while controlling for differences in patient characteristics. RESULTS: Patients' perceptions of care received within settings showed high scores for the factors and single items "honesty" (ID) and "atmosphere" (S) in all settings and low scores for "exhaustion" (MT) in three out of four settings. Patients' perceptions of importance scored high for "medical care" (S), "honesty" (ID), "respect and empathy" (ID) and "atmosphere" (S) in all settings. No aspects of care scored low in all settings. Importance scored higher than perceptions of care received, in particular for receiving information. Patients' perceptions of care across settings differed, with highest scores in hospice inpatient care for the dimensions; ID, SC, and "medical care" (S), the SC and "atmosphere" (S) for hospice day care, and "medical care" (S) for palliative units in nursing homes. There were no differences in subjective importance across settings. CONCLUSION: Strengths of services related to identity orientation approach and a pleasant and safe atmosphere. Key areas for improvement related to receiving information. Perceptions of subjective importance did not differ across settings, but perceptions of care received scored higher in more care areas for hospice inpatient care, than in other settings. Further studies are needed to support these findings, to investigate why perceptions of care differ across settings and to highlight what can be learned from settings receiving high scores. PMID- 27553777 TI - Negative spot sign in primary intracerebral hemorrhage: potential impact in reducing imaging. AB - Intracerebral hemorrhage (ICH) is one of the most devastating and costly diagnoses in the USA. ICH is a common diagnosis, accounting for 10-15 % of all strokes and affecting 20 out of 100,000 people. The CT angiography (CTA) spot sign, or contrast extravasation into the hematoma, is a reliable predictor of hematoma expansion, clinical deterioration, and increased mortality. Multiple studies have demonstrated a high negative predictive value (NPV) for ICH expansion in patients without spot sign. Our aim is to determine the absolute NPV of the spot sign and clinical characteristics of patients who had ICH expansion despite the absence of a spot sign. This information may be helpful in the development of a cost effective imaging protocol of patients with ICH. During a 3 year period, 204 patients with a CTA with primary intracerebral hemorrhage were evaluated for subsequent hematoma expansion during their hospitalization. Patients with intraventricular hemorrhage were excluded. Clinical characteristics and antithrombotic treatment on admission were noted. The number of follow-up NCCT was recorded. Of the resulting 123 patients, 108 had a negative spot sign and 7 of those patients subsequently had significant hematoma expansion, 6 of which were on antithrombotic therapy. The NPV of the CTA spot sign was calculated at 0.93. In patients without antithrombotic therapy, the NPV was 0.98. In summary, the negative predictive value of the CTA spot sign for expansion of ICH, in the absence of antithrombotic therapy and intraventricular hemorrhage (IVH) on admission, is very high. These results have the potential to redirect follow-up imaging protocols and reduce cost. PMID- 27553778 TI - The red connection: a review of aortic and arterial fistulae with an emphasis on CT findings. AB - Fistulae between the aorta and adjacent structures are a rare, emergent, and potentially life-threatening process. Most commonly, aortic fistulae arise secondarily as a complication of prior aortic surgery with fistulization to adjacent structures. Rarely, a primary fistula may arise from the aorta in the setting of a pre-existing aneurysm or from a mass, inflammation, or infection. Although the incidence of aortic fistulae remains low, the frequency continues to increase as aortic surgical interventions and post-surgical follow-up with imaging become more common. Computed tomography (CT) is the modality of choice in evaluating the patient with suspected aortic fistula because of its accessibility and short scan time. In addition, CT allows for more clear depiction of para aortic or intra-aortic gas than ultrasound or magnetic resonance (MR). This gas may be the first clue of a fistula. Given the high mortality associated with aortic fistulae, familiarity with the imaging findings of the spectrum of aortic fistulae is essential knowledge in the emergency setting. This review will discuss the imaging appearance of aortic and arterial fistulae to the bronchi, esophagus, gastrointestinal tract, ureters, and veins on CT. PMID- 27553779 TI - Delivery of Copper-chelating Trientine (TETA) to the central nervous system by surface modified liposomes. AB - The existence of the blood-brain barrier (BBB) complicates the treatment of many central nervous system (CNS) disorders, including the copper storage disease, Wilson's disease. Its CNS symptoms represent a serious problem, since therapeutics for Wilson's disease do not cross the BBB. One strategy to overcome this obstacle is the transfer of drugs across the BBB with colloidal carrier systems like liposomes. The aim of the present study was to encapsulate triethylenetetramine (TETA), a copper chelating agent, into surface modified liposomes and to investigate their permeation across the BBB. Liposomes were modified with cationized bovine serum albumin or penetratin, a cell penetrating peptide. Liposomes were characterized regarding size, PDI, zeta potential and encapsulation efficiency. Size was between 139.4+/-1.9nm to 171.1+/-3.5nm with PDI's below 0.2. Zeta potentials of vectorized liposomes were at least 6.9mV higher than those of standard liposomes. Cryo-TEM micrographs displayed liposomal structure, integrity and the similarity of structure and size between loaded, unloaded, vectorized and non- vectorized liposomes. In vivo experiments in rats showed an up to 16-fold higher brain uptake of TETA in vectorized liposomes compared to free TETA or TETA in non-vectorized liposomes, proving successful brain delivery using target seeking surface modifications. Tissue analysis indicated TETA concentrations in the brain being high enough to treat Wilson's disease. PMID- 27553780 TI - Saturated fatty acids and fatty acid esters promote the polymorphic transition of clarithromycin metastable form I crystal. AB - The phase transition of active pharmaceutical ingredients should be taken into account during manufacturing, processing- and storage, because different crystal forms lead to different physical properties of formulations. The phase transition of clarithromycin (CAM) metastable form I to stable form II was investigated on heating with additives such as fatty acids or fatty acid esters. Differential scanning calorimetry analyses revealed that when form I was heated with additives, the phase transition temperature of form I decreased close to the melting points of the additives. Powder X-ray diffraction analyses indicated the tentative presence of a non-crystalline component during the transition of form I to form II on heating with additives. These observations implied that CAM form I dissolved in the melted additives on heating and the dissolved CAM crystallized to form II. Reduction of transition temperatures in the presence of additives were also observed for the crystals of nifedipine form B and carbamazepine form III. These results suggested that the phenomena can be widely applicable for simultaneous crystalline phase transition and granulation using binder additives. PMID- 27553782 TI - 3D Graphene Aerogels Decorated with Cobalt Phosphide Nanoparticles as Electrocatalysts for the Hydrogen Evolution Reaction. AB - The development of non-precious-metal hydrogen evolution reaction (HER) electrocatalysts with high activity and excellent durability in acidic media is of significant importance for renewable energy research. We report a novel electrocatalyst based on a three-dimensional (3D) graphene aerogel decorated with cobalt phosphide nanoparticles (CoP/GA). The material has a unique hierarchical porous structure with CoP nanoparticles encapsulated uniformly within the graphene sheets. The optimized catalyst shows superior activity, with an overpotential of only 121 mV at 10 mA cm-2 , a Tafel slope of 50 mV dec-1 , and an exchange current density of 0.105 mA cm-2 , and it maintains its catalytic activity for at least 13 h. More importantly, this work provides a versatile way for the rational design and fabrication of 3D graphene-based multifunctional composite materials. PMID- 27553781 TI - Cilia are required for asymmetric nodal induction in the sea urchin embryo. AB - BACKGROUND: Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. RESULTS: Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. CONCLUSIONS: Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia based symmetry breakage is a synapomorphy of the deuterostomes. PMID- 27553783 TI - Fecal carbon and nitrogen isotopic analysis as an indicator of diet in Kanyawara chimpanzees, Kibale National Park, Uganda. AB - OBJECTIVES: The shorter-term overview from feces provides scope to investigate dietary fluctuations. We assess the correlation of stable isotopic fecal values with recorded seasonal diet of 10 adult chimpanzees (P. t. schweinfurthii) of the Kanyawara community (Kibale National Park, Uganda) and whether fecal nitrogen levels (%N) indicate a change in crude protein intake. MATERIALS AND METHODS: We recorded food eaten by each ape and collected both concurrent fecal samples (N = 115) and plant foods eaten by this community (N = 64). We compared fecal delta13 C and delta15 N values (also %N) with: (a) plant values; (b) feeding data; and (c) food-items found macroscopically in the fecal samples. Interspecies and intraspecies differences in plant and fecal isotope values (and %N) as well as seasonality in diet were determined using parametric and nonparametric tests. RESULTS: No difference in plant delta13 C and delta15 N values was found at intraspecies or interspecies level. Fecal isotope values reflected a diet of C3 plants from evergreen forest vegetation. Seasonal differences in delta13 C and delta15 N corresponded with aspects of feeding and fecal macroscopic data, but only at community level. A change in crude protein intake was not indicated from %N content. DISCUSSION: This study further validates the use of staple isotope analyses of primate feces to provide a dietary overview, revealing seasonal differences at community level; however, conclusive results may be limited for individuals when using short sampling periods. Further study of variables that influence fecal %N content is also suggested to interpret crude protein intake. PMID- 27553786 TI - Learning: a very short introduction. PMID- 27553787 TI - Electronic structures and enhanced optical properties of blue phosphorene/transition metal dichalcogenides van der Waals heterostructures. AB - As a fast emerging topic, van der Waals (vdW) heterostructures have been proposed to modify two-dimensional layered materials with desired properties, thus greatly extending the applications of these materials. In this work, the stacking characteristics, electronic structures, band edge alignments, charge density distributions and optical properties of blue phosphorene/transition metal dichalcogenides (BlueP/TMDs) vdW heterostructures were systematically studied based on vdW corrected density functional theory. Interestingly, the valence band maximum and conduction band minimum are located in different parts of BlueP/MoSe2, BlueP/WS2 and BlueP/WSe2 heterostructures. The MoSe2, WS2 or WSe2 layer can be used as the electron donor and the BlueP layer can be used as the electron acceptor. We further found that the optical properties under visible light irradiation of BlueP/TMDs vdW heterostructures are significantly improved. In particular, the predicted upper limit energy conversion efficiencies of BlueP/MoS2 and BlueP/MoSe2 heterostructures reach as large as 1.16% and 0.98%, respectively, suggesting their potential applications in efficient thin-film solar cells and optoelectronic devices. PMID- 27553785 TI - A retrospective chart review study to describe selected zoonotic and arboviral etiologies in hospitalized febrile patients in the Republic of Armenia. AB - BACKGROUND: Scant information is available on the infectious causes of febrile illnesses in Armenia. The goal of this study was to describe the most common causes, with a focus on zoonotic and arboviral infections and related epidemiological and clinical patterns for hospitalized patients with febrile illnesses of infectious origin admitted to Nork Infectious Diseases Clinical Hospital, the referral center for infectious diseases in the capital city, Yerevan. METHOD: A chart review study was conducted in 2014. Data were abstracted from medical charts of adults (>=18 years) with a fever (>=38 degrees C), who were hospitalized (for >=24 h) in 2010-2012. RESULTS: Of the 600 patients whose charts were analyzed, 76 % were from Yerevan and 51 % were male; the mean age (+/ standard deviation) was 35.5 (+/-16) years. Livestock exposure was recorded in 5 % of charts. Consumption of undercooked meat and unpasteurized dairy products were reported in 11 and 8 % of charts, respectively. Intestinal infections (51 %) were the most frequently reported final medical diagnoses, followed by diseases of the respiratory system (11 %), infectious mononucleosis (9.5 %), chickenpox (8.3 %), brucellosis (8.3 %), viral hepatitis (3.2 %), and erysipelas (1.5 %). Reviewed medical charts included two cases of fever of unknown origin (FUO), two cutaneous anthrax cases, two leptospirosis cases, three imported malaria cases, one case of rickettsiosis, and one case of rabies. Engagement in agricultural activities, exposure to animals, consumption of raw or unpasteurized milk, and male gender were significantly associated with brucellosis. CONCLUSION: Our analysis indicated that brucellosis was the most frequently reported zoonotic disease among hospitalized febrile patients. Overall, these study results suggest that zoonotic and arboviral infections were not common etiologies among febrile adult patients admitted to the Nork Infectious Diseases Clinical Hospital in Armenia. PMID- 27553784 TI - The Gut-Brain Axis, BDNF, NMDA and CNS Disorders. AB - Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders. PMID- 27553788 TI - Appropriate Use Criteria for Echocardiography: Evolving Applications in the Era of Value-Based Healthcare. AB - The current climate in healthcare is increasingly emphasizing a value-based approach to diagnostic testing. Cardiac imaging, including echocardiography, has been a primary target of ongoing reforms in healthcare delivery and reimbursement. The Appropriate Use Criteria (AUC) for echocardiography is a physician-derived tool intended to guide utilization in optimal patient care. To date, the AUC have primarily been employed solely as justification for reimbursement, though evolving broader applications to guide clinical decision making suggest a far more valuable role in the delivery of high-quality and high value healthcare. PMID- 27553789 TI - Chemically Inhomogeneous RE-Fe-B Permanent Magnets with High Figure of Merit: Solution to Global Rare Earth Criticality. AB - The global rare earth (RE) criticality, especially for those closely-relied Nd/Pr/Dy/Tb in the 2:14:1-typed permanent magnets (PMs), has triggered tremendous attempts to develop new alternatives. Prospective candidates La/Ce with high abundance, however, cannot provide an equivalent performance due to inferior magnetic properties of (La/Ce)2Fe14B to Nd2Fe14B. Here we report high figure-of merit La/Ce-rich RE-Fe-B PMs, where La/Ce are inhomogeneously distributed among the 2:14:1 phase. The resultant exchange coupling within an individual grain and magnetostatic interactions across grains ensure much superior performance to the La/Ce homogeneously distributed magnet. Maximum energy product (BH)max of 42.2 MGOe is achieved even with 36 wt. % La-Ce incorporation. The cost performance, (BH)max/cost, has been raised by 27.1% compared to a 48.9 MGOe La/Ce-free commercial magnet. The construction of chemical heterogeneity offers recipes to develop commercial-grade PMs using the less risky La/Ce, and also provides a promising solution to the REs availability constraints. PMID- 27553790 TI - Indocyanine green fluorescence angiography during laparoscopic low anterior resection: results of a case-matched study. AB - INTRODUCTION: Colorectal anastomoses after anterior resection for cancer carry a high risk of leakage. Different factors might influence the correct healing of anastomosis, but adequate perfusion of the bowel is highlighted as one of the most important elements. Fluorescence angiography (FA) is a new technique that allows the surgeon to perform real-time intraoperative angiography to evaluate the perfusion of the anastomosis and hence, potentially, reduce leak rate. AIM: The aim of this study was to evaluate the impact of FA of the bowel on postoperative complications and anastomotic leakage after laparoscopic anterior resection with total mesorectal excision (TME). METHODS: FA was performed in all patients undergoing laparoscopic anterior resection with TME for cancer followed by colorectal or coloanal anastomosis. Results were compared to a historical controls group of 38 patients previously operated by the same surgeon for the same indication but without the use of FA. RESULTS: From October 2014 to November 2015, 42 patients underwent laparoscopic anterior resection with TME and FA of the bowel. The surgeon subjectively decided to change the planned anastomotic level of the descending colon due to hypoperfused distal segment in two out of 42 patients in the FA group (4.7 %). Anastomotic leakage, confirmed by postoperative CT scan and water-soluble contrast enema, was found in two cases of a historical controls group and none in the FA group. No adverse events (side effects or allergic reaction) related to FA were recorded. All the other postoperative complications were comparable between the two groups. CONCLUSION: In our experience, ICG FA was safe and effective in low rectal cancer resection, possibly leading to a reduction in the anastomotic leakage rate after TME. PMID- 27553791 TI - Learning curve for single-port laparoscopic colon cancer resection: a multicenter observational study. AB - BACKGROUND: The aim of this study was to investigate the learning curves (LCs) of single-port laparoscopic surgery (SPLS) for colon cancer using multidimensional statistical analyses. Although SPLS yields better cosmetic results and comparable short-term outcomes compared to conventional laparoscopic surgery, its technical difficulties make surgeons hesitant to try SPLS. Moreover, the LCs of SPLS for colon cancer are not well delineated. METHODS: Data were collected from patients who underwent SPLS for colon cancer in seven Korean institutions between May 2009 and May 2015. The LCs were analyzed using the moving average method and the cumulative sum control chart (CUSUM) for operation time and surgical failure. Surgical failure was defined as the any conversion, postoperative complications, or less than 12 harvested lymph nodes from surgical specimens. RESULTS: A total of 356 patients were included in this study. Six and three surgeons performed 282 anterior resections (ARs) and 74 right colectomies (RCs), respectively. On the basis of the moving average method and CUSUM for operation time and surgical failure, the LCs for AR were 18, 16, 35, 13, 36, and 13 cases for surgeons A-F, respectively. However, the LCs for RC were 6 and 15 cases for surgeons D and E, respectively, and were ambiguous for one surgeon. CONCLUSIONS: For surgeons experienced in conventional laparoscopic colorectal surgery, the LCs of SPLS for colon cancer ranged from 6 to 36 cases, which is shorter than the LCs reported for conventional laparoscopic surgery. PMID- 27553792 TI - Impact of prior interventions on outcomes during per oral endoscopic myotomy. AB - BACKGROUND: Per oral endoscopic myotomy (POEM) is performed by accessing the submucosal space of the esophagus. This space may be impacted by prior interventions such as submucosal injections, dilations or previous myotomies. These interventions could make POEM more difficult and may deter surgeons during their initial experience. We sought to determine the impact of prior interventions on our early experience. METHODS: Prospective, single-center study of consecutive patients undergoing POEM. Patients were grouped according to their anticipated complexity: Group A: no prior interventions (N = 19); Group B: prior interventions such as submucosal injections and/or dilations (N = 11) and Group C: sigmoidal esophagus, prior esophageal surgery, balloon dilation >30 mm (N = 8). We compared operative times, inadvertent mucosotomy rates, complications and short-term outcomes between groups. RESULTS: A total of 38 patients underwent POEM for achalasia subtypes: I (N = 9), II (N = 19) and III (N = 7). Three had other dysmotility disorders. Patients between the groups were similar. Operative times were similar between Group A and Group B but significantly longer for Group C (133 vs. 132 vs. 210 min, p = 0.001). Mucosotomy rates were highest in Group A (6/19) with 1 each in Group B/C (p = 0.46). One patient in Group A required an esophageal stent. Eckardt scores improved in all groups (6-1; 8-2; 6-0.5, p = 0.73), and postoperative GERD-HRQL scores were similar. One patient underwent laparoscopic myotomy for persistent symptoms with no improvement, and one patient underwent esophagectomy for a sigmoid esophagus and persistent symptoms despite adequate myotomy. CONCLUSION: A prior intervention does not seem to impact short term clinical outcomes with POEM. Patients who had submucosal injections or small caliber dilations are similar to patients with no prior inventions; however, patients with a sigmoid-shaped esophagus and/or a prior myotomy require nearly double the operative time. Endoscopists undertaking POEM should consider these during their learning curve. PMID- 27553793 TI - Weight regain following RYGB can be effectively treated using a combination of endoscopic suturing and sclerotherapy. AB - BACKGROUND: Obesity is a leading cause of morbidity and healthcare utilization. At the moment, the best treatment for obesity has shown to be laparoscopic gastric bypass. However, about a quarter of the patients experience substantial weight regain, which is difficult to treat, as revision surgery has higher risks than primary procedures. Endoscopic procedures, such as endoscopic suturing, are effective, safe and less invasive in addressing weight regain. METHODS: We conducted a retrospective analysis on 22 consecutive patients operated between 2011 and 2013 who had a significant weight regain after RYGB (mean follow-up 22 months), in order to evaluate the long-term outcomes of endoscopic gastro-jejunal revision after weight regain post-bypass surgery. Mucosal ablation around the anastomosis was performed in all patients, and the endoscopic suturing device was used to perform suture stoma reduction. We also evaluated, in a group of 11 patients, the effect of combining sclerotherapy and endoscopic suturing. RESULTS: We showed good efficacy of the endoluminal procedure, with 100 % of patients achieving weight loss. Maximum weight loss was noted at a mean of 18-month follow up (average of 60.3 % excess weight loss; n = 19), while the mean weight loss regained percentage was 5 % +/- 39. 4/22 patients (all four in non-sclerotherapy group, all of them had an anastomosis >10 mm) regained some of this lost weight by the time of the longest follow-up. There was an actual correlation between final stoma diameter (<10 mm) and weight loss. CONCLUSIONS: A larger randomized sample of patients with a longer follow-up would be needed to support the effectiveness of the combination of the two therapies. Although almost 20 % of the patients regained weight during the follow-up period, the endoluminal approach offers the advantage of being repeatable after weight regain without adding morbidity risks. PMID- 27553794 TI - Management of laparoscopic adjustable gastric band erosion. AB - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) was a popular procedure in the USA and Europe in the past decade. However, its use has currently declined. Band erosion (BE) is a rare complication after LAGB with a reported incidence rate of 1.46 %. Controversies exist regarding the management, approach and timing for the band removal. The aim of this study is to describe the rate, clinical presentation and perioperative outcomes of BEs at our institution and provide overall recommendations regarding the diagnosis and management of BE. MATERIALS AND METHODS: This study is a single-center, retrospective review of a prospectively maintained database. Data were collected from all consecutive patients who underwent a LAGB and band revisional surgeries at the University of Illinois Hospital and Health Sciences System from December 2008 to September 2015. We identified patients who underwent gastric band removal due to a BE and analyzed their outcomes. RESULTS: A total of 576 LAGBs were performed at our institution. Nine patients underwent surgery for BE at our hospital. The average time between the primary surgery and the removal of the band was 68.5 (42.9) months. Abdominal pain, nausea and/or vomiting were the most frequently mentioned symptoms. In all patients, a minimally invasive approach was used to remove the band. The mean length of hospitalization was 2.6 (1.1) days. The only complication was a pneumonia (n = 1). CONCLUSIONS: BE is one of the most severe complications of LAGB. The minimally invasive approach provided us with the opportunity to repair the fistula, and it was associated with a prompt recovery with very little morbidity. In general, it is recommended that the band be removed at the time of the diagnosis of the BE. Endoscopic band removal can be utilized with patients who have a more advanced BE and migration into the gastric lumen. PMID- 27553795 TI - A short or a long Roux limb in gastric bypass surgery: does it matter? AB - BACKGROUND: The Roux-en-Y gastric bypass (RYGB) still remains the gold standard in bariatric surgery. However, no consensus exists on the optimal limb lengths to induce maximum weight reduction. The aim of the present study was to assess the effect of a longer alimentary limb (AL) length on weight reduction after RYGB. METHODS: A retrospective analysis of a prospectively collected database of patients who underwent a primary laparoscopic RYGB between January 2001 and March 2011 was performed. Patients received a short AL (SAL; 100 cm) or a long AL (LAL; 150 cm). Primary outcome was weight loss, and secondary outcomes were short- and long-term complication rates. RESULTS: A total of 768 patients received a RYGB during the study period. Of these, 730 consecutive patients were included for long-term analysis and had a mean follow-up (FU) of 37 +/- 26 [range 0-120] months; 360 (47 %) patients received a SAL RYGB. Overall %TBWL was 33 +/- 9 % after 2 years (FU 74 %) and 28 +/- 12 % after 5 years (FU 20 %). No significant differences in %TBWL were found between SAL RYGB and LAL RYGB during the study period. The 30-day mortality rate was 0.13, 9 % overall short-term complication rate and 19 % cumulative long-term complication rate. No differences in complications were found between SAL and LAL RYGB patients. CONCLUSION: Lengthening of the alimentary limb from 100 to 150 cm did not affect post-RYGB weight loss. Overall complication rates were low and comparable in this series of RYGB patients. PMID- 27553797 TI - Erratum to: Roux-en-Y fistulo-jejunostomy as a salvage procedure in patients with post-sleeve gastrectomy fistula: mid-term results. PMID- 27553796 TI - Prevertebral cervical approach: a pure endoscopic surgical technique for posterior mediastinum parathyroid adenomas. AB - BACKGROUND: Parathyroid gland mediastinal ectopia is an unusual but challenging condition in surgical management of hyperparathyroidism. Posterior mediastinum parathyroid ectopia is rare, and glands need to be removed either with a broad open cervical or thoracic approach. In recent years, several minimally invasive approaches to mediastinal parathyroid glands have been described, but for posterior mediastinum adenomas, proposed techniques are transthoracic. METHODS: The aim of this paper is to describe, to our best knowledge for the first time, a standardized pure endoscopic cervical technique to approach posterior mediastinal parathyroid adenomas which we have used in three patients. RESULTS: The technique was applied in three patients which excellent surgical, postoperative, and cosmetic results. CONCLUSIONS: Endoscopic prevertebral approach is a feasible, sure and inexpensive standardized pure endoscopic cervical approach to posterior mediastinal parathyroid adenomas, which may result in a less aggressive surgical option when compared with thoracic approaches. PMID- 27553798 TI - Surgical anatomy of the supracarinal esophagus based on a minimally invasive approach: vascular and nervous anatomy and technical steps to resection and lymphadenectomy. AB - BACKGROUND: During esophageal dissection and lymphadenectomy of the upper mediastinum by thoracoscopy in prone position, we observed a complex anatomy in which we had to resect the esophagus, dissect vessels and nerves, and take down some of these in order to perform a complete lymphadenectomy. In order to improve the quality of the dissection and standardization of the procedure, we describe the surgical anatomy and steps involved in this procedure. METHODS: We retrospectively evaluated twenty consecutive and unedited videos of thoracoscopic esophageal resections. We recorded the vascular anatomy of the supracarinal esophagus, lymph node stations and the steps taken in this procedure. The resulting concept was validated in a prospective study including five patients. RESULTS: Seventy percent of patients in the retrospective study had one right bronchial artery (RBA) and two left bronchial arteries (LBA). The RBA was divided at both sides of the esophagus in 18 patients, with preservation of one LBA or at least one esophageal branch in all cases. Both recurrent laryngeal nerves were identified in 18 patients. All patients in the prospective study had one RBA and two LBA, and in four patients the RBA was divided at both sides of the esophagus and preserved one of the LBA. Lymphadenectomy was performed of stations 4R, 4L, 2R and 2L, with a median of 11 resected lymph nodes. Both recurrent laryngeal nerves were identified in four patients. In three patients, only the left recurrent nerve could be identified. Two patients showed palsy of the left recurrent laryngeal nerve, and one showed neuropraxia of the left vocal cord. CONCLUSIONS: Knowledge of the surgical anatomy of the upper mediastinum and its anatomical variations is important for standardization of an adequate esophageal resection and paratracheal lymphadenectomy with preservation of any vascularization of the trachea, bronchi and the recurrent laryngeal nerves. PMID- 27553799 TI - Outcome of acute perforated cholecystitis: a register study of over 5000 cases from a quality control database in Germany. AB - BACKGROUND: Acute perforated cholecystitis (APC) is probably the most severe complication of acute cholecystitis. However, data on the outcome of cholecystectomy for APC are limited to small series. This study investigated the outcomes of cholecystectomy for APC. METHODS: Data from a prospectively maintained quality control database in Germany were analyzed. Cases with APC were compared to cases without gallbladder perforation with regard to demographic characteristics, clinical findings and surgical outcomes. RESULTS: A total of 5704 patients with APC were compared to 39,661 patients without perforation. Risk factors for APC included: the male gender, advanced age (>65 years), ASA score >2, elevated white blood count (WBC), positive findings on abdominal ultrasound sonography and fever. The APC group differed significantly from the control group with regard to fever (29.8 vs. 12.2 %), elevated WBC (83.8 vs. 65.4 %) and positive findings from ultrasound sonography (84.9 vs. 78.9 %), p < 0001. Preoperative computed tomography (CT) was ordered significantly more often in the APC group compared to the control group (2.3 vs. 1.0 %, p = 0.001). Surgery lasted significantly longer in the APC group (92.3 +/- 40.8 vs. 73.7 +/- 34.1, p < 0.001). The rates of conversion (18.9 vs. 6.8 %), bile duct injury (1.4 vs. 0.5 %), re-intervention (6.9 vs. 2.9 %) and mortality (4.3 vs. 1.3 %) were significantly higher in the APC group (p < 0.001). Similarly, the length of stay (13.4 +/- 11.4 vs. 9.0 +/- 8.3, p < 0.001) was significantly longer in the APC group. CONCLUSION: Acute perforated cholecystitis is a severe complication of acute cholecystitis. Surgical dissection could be challenging with high risks of bile duct injury and conversion. The rates of morbidity and mortality are higher compared to those of patients without perforation. PMID- 27553800 TI - Endoscopic resection for duodenal subepithelial tumors: a single-center experience. AB - BACKGROUND: Subepithelial tumors (SETs) in the gastrointestinal tract are often incidentally found during endoscopic examinations. Although the utility and safety of endoscopic resection (ER) of SETs in the esophagus and stomach have been described, data about the ER of duodenal SETs remain scant. Therefore, we aimed to investigate the clinical outcomes associated with the ER of duodenal SETs and to assess possible predictive factors for incomplete resection. METHODS: We conducted a retrospective observational study of 62 patients (64 lesions) that underwent ER of duodenal SETs between June 2005 and December 2015 at the Pusan National University Hospital. The therapeutic outcomes from ER and procedure related complications were analyzed. RESULTS: Endoscopic mucosal resection (EMR) was performed in 38 tumors, EMR with a ligation device (EMR-L) in 18 and endoscopic submucosal dissection (ESD) in 8. The overall en bloc resection and complete ER rates were 96.9 % (62/64) and 100 % (64/64), respectively. The complete pathologic resection rate was 76.6 % (49/64). Multivariate logistic regression analyses determined that the macroscopic type (Yamada type I or II; odds ratio [OR] 6.460, 95 % confidence interval [CI] 1.569-37.458, p = 0.027) and the treatment method (ESD; OR 7.178, 95 % CI 1.291-39.323, p = 0.024) were independently associated with incomplete pathologic resection. The procedure related bleeding and perforation rates were 6.3 % and 4.7 %, respectively. No recurrences were observed in patients who had undergone complete ER at a median follow-up period of 20 months (range 6-112 months). CONCLUSION: ER is an effective, safe, and feasible treatment for duodenal SETs, especially when the SET is located in the deep mucosal layer and/or the submucosal layer. PMID- 27553801 TI - Effectiveness and safety of single-port versus multi-port laparoscopic surgery for treating liver diseases: a meta-analysis. AB - OBJECTIVE: To compare the effectiveness and safety of single-port versus multi port laparoscopic surgery for treating liver diseases. METHODS: Several databases were systematically searched for randomized controlled trials, cohort studies, and case-control studies on the use of single-port versus multi-port laparoscopic surgery to treat liver diseases from their inception until March 24, 2016. The primary outcomes were the operative time, volume of intraoperative blood loss, rate of postoperative complications, median length of postoperative stay, recovery time of gastrointestinal function, volume of postoperative drainage, and postoperative drainage time. The study-specific effect sizes and their 95 % confidence interval were all combined to calculate the pooled value by using a random-effects model. RESULTS: A total of nine studies were included, which involved 277 patients. The total and subgroup data were combined by meta analysis. This meta-analysis showed that single-port and multi-port laparoscopic liver surgery for treating liver diseases did not differ in terms of operative time (P = 0.48), rate of postoperative complications (P = 0.56), median length of postoperative stay (P = 0.80), and recovery time of gastrointestinal function (P = 0.54). For liver diseases, the single-port group exhibited a lower volume of intraoperative blood loss than that presented by the multi-port group (P = 0.0006). In the hepatic resection subgroup, a lower volume of intraoperative blood loss was noted in the single-port group (P < 0.0001). By contrast, in the hepatic cyst subgroup, the single-port group showed a higher volume of intraoperative blood loss (P = 0.02) but a shorter median length of postoperative stay (P = 0.02). The findings of the potential subgroup analysis in these outcomes were consistent with the total data. CONCLUSION: Compared with multi port laparoscopic surgery, the single-port method showed comparable effectiveness and safety for the treatment of liver diseases in terms of current evidence. PMID- 27553802 TI - Relationship between stoma creation route for end colostomy and parastomal hernia development after laparoscopic surgery. AB - BACKGROUND: The therapeutic benefits of extraperitoneal colostomy with laparoscopic surgery remain unclear. The aim of this study was to investigate the relationship between the route for stoma creation with laparoscopic surgery and stoma-related complications, especially parastomal hernia (PSH). METHODS: From January 2007 to March 2015, a total of 59 patients who underwent laparoscopic abdominoperineal resection or Hartmann procedure were investigated. Patient demographic and treatment characteristics, including stoma-related complications, were analyzed retrospectively. RESULTS: Transperitoneal and extraperitoneal colostomy were performed in 29 and 30 patients, respectively. Median follow-up duration was 21 months (range: 2-95). Patient demographic and treatment characteristics were comparable between the transperitoneal group (TPG) and the extraperitoneal group (EPG). PSH developed in 12 (41 %) patients in TPG, and 4 (13 %) patients in EPG (p = 0.020). The incidence of other stoma-related complications and non-stoma-related complications did not differ significantly between TPG and EPG. No patient characteristics except for transperitoneal route for stoma creation were associated with PSH development. CONCLUSIONS: The extraperitoneal route for stoma creation is associated with a significantly lower incidence of PSH development after laparoscopic surgery. Whenever possible, extraperitoneal colostomy should be recommended, even with laparoscopic surgery. PMID- 27553803 TI - Efficacy of magnetic sphincter augmentation in patients with large hiatal hernias. AB - BACKGROUND: Magnetic sphincter augmentation (MSA) has demonstrated long-term safety and efficacy in the treatment of patients with gastroesophageal reflux (GERD), but its efficacy in patients with large hiatal hernias has yet to be proven. The aim of our study was to assess outcomes of MSA in patients with hiatal hernias >=3 cm. METHODS: We retrospectively reviewed all patients who underwent MSA at our institutions over a 6-year period. Information obtained consisted of patient demographics, symptoms of GERD, preoperative GERD Health Related Quality-of-Life (HRQL) scores, perioperative details, and implantation of the MSA device. Primary endpoints included postoperative GERD-HRQL scores, proton pump inhibitor (PPI) use, symptom change, and procedure-related complications. A large hiatal hernia was defined as a hernia measuring >=3 cm by intraoperative measurement. RESULTS: A total of 192 patients were reviewed. Median follow-up was 20 months (3-75 months). Mean GERD-HRQL scores in the overall population before and after MSA were 18.9 and 5.0, respectively (p < 0.001). In the majority of patients symptoms improved or resolved (N = 177, p < 0.001). Fifty-two patients (27.0 %) had a hiatal hernia >=3 cm (range 3-7 cm). Their mean GERD-HRQL score decreased from 20.5 to 3.6 (p < 0.001) following MSA. When compared to patients with smaller hernias, patients with large hiatal hernias had decreased postoperative PPI requirement (9.6 vs. 26.6 %, p = 0.011) and lower mean postoperative GERD-HRQL scores (3.6 vs. 5.6, p = 0.027). The percent of patients requiring postoperative intervention for dysphagia was similar (13.5 vs. 17.9 %, p = 0.522), as was the incidence of symptom resolution or improvement (98.1 vs. 91.3 %, p = 0.118). CONCLUSION: MSA in patients with large hiatal hernias demonstrates decreased postoperative PPI requirement and mean GERD-HRQL scores compared to patients with smaller hernias. The incidence of symptom resolution or improvement and the percentage of patients requiring intervention for dysphagia are similar. Short-term outcomes of MSA are encouraging in patients with gastroesophageal reflux disease and large hiatal hernias. PMID- 27553804 TI - Compliance of the abdominal wall during laparoscopic insufflation. AB - BACKGROUND: To provide adequate workspace between the viscera and abdominal wall, insufflation with carbon dioxide is a common practice in laparoscopic surgeries. An insufflation pressure of 15 mmHg is considered to be safe in patients, but all insufflation pressures create perioperative and postoperative physiologic effects. As a composition of viscoelastic materials, the abdominal wall should distend in a predictable manner given the pressure of the pneumoperitoneum. The purpose of this study was to elucidate the relationship between degree of abdominal distention and the insufflation pressure, with the goal of determining factors which impact the compliance of the abdominal wall. METHODS: A prospective, IRB-approved study was conducted to video record the abdomens of patients undergoing insufflation prior to a laparoscopic surgery. Photo samples were taken every 5 s, and the strain of the patient's abdomen in the sagittal plane was determined, as well as the insufflator pressure (stress) at bedside. Patients were insufflated to 15 mmHg. The relationship between the stress and strain was determined in each sample, and compliance of the patient's abdominal wall was calculated. Subcutaneous fat thickness and rectus abdominus muscle thickness were obtained from computed tomography scans. Correlations between abdominal wall compliances and subcutaneous fat and muscle content were determined. RESULTS: Twenty-five patients were evaluated. An increased fat thickness in the abdominal wall had a direct exponential relationship with abdominal wall compliance (R 2 = 0.59, p < 0.05). There was no correlation between muscle and fat thickness. CONCLUSION: All insufflation pressures create perioperative and postoperative complications. The compliance of patients' abdominal body walls differs, and subcutaneous fat thickness has a direct exponential relationship with abdominal wall compliance. Thus, insufflation pressures can be better tailored per the patient. Future studies are needed to demonstrate the clinical impact of varying insufflation pressures. PMID- 27553805 TI - Barrett's esophagus after Roux-en-Y gastric bypass: does regression occur? AB - INTRODUCTION: Barrett's esophagus (BE) is recognized as a premalignant lesion for esophageal adenocarcinoma. BE appears as a consequence of gastroesophageal reflux disease (GERD), which is increased among obese population. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the best treatment option for obesity combined with GERD. However, data on evolution of BE after LRYGB are scarce. METHODS AND PROCEDURES: Patients were studied with esophagogastroduodenoscopy (EGD) and gastric biopsy preoperatively. If BE was suspected, esophageal biopsy was performed. If BE was confirmed, LRYGB was indicated with yearly surveillance EGD with biopsies. LRYGB patients who had BE with at least 1-year follow-up were included. RESULTS: Between 10/07 and 1/16, 2144 patients underwent laparoscopic bariatric surgery at our institution. There were 1681 (78 %) LRYGB, 399 (19 %) laparoscopic sleeve gastrectomies, and 64 (3 %) revisions. Nineteen patients (0.9 %) had BE preoperatively, and they all underwent LRYGB; 11 of them (58 %) were eligible for this study. There were 6 women and 5 men, mean age 49 +/- 11 years, initial BMI 44 +/- 6 kg/m2. Mean follow-up was 41 +/- 31 months; there were 9 short-segment BE (SSBE) and 2 long-segment BE (LSBE). On pre- and post-op EGD, BE length was 2.1 +/- 1.6 and 1.2 +/- 1.2 cm, respectively (p = NS). Post-op EGD was compatible with BE in all cases, although esophageal biopsy showed remission in 4 (36 %) cases: three short-segment BE (SSBE) and one long-segment BE (LSBE). One patient was indefinite for dysplasia and remained the same after the operation. CONCLUSION: Our preliminary data showed that LRYGB is a suitable treatment option for obese patients with BE, demonstrated by 36 % regression rate of this premalignant disease. Although BE persisted in the remaining patients, no progression to dysplasia was observed. A larger number of patients and longer follow-up are needed for more definitive conclusions. PMID- 27553806 TI - Evaluation of the anticoagulant effect and timing of the concomitant use of S-1 and warfarin. AB - Objectives To evaluate the effects of the timing of warfarin (WF) administration in patients with gastric cancer who received S-1 oral chemotherapy. Methods This retrospective chart review collected patient data including the prothrombin time international normalized ratio (PT-INR). Patients were categorized into three groups based on the timing of WF administration in relation to S-1 oral chemotherapy: group A patients received WF before S-1 chemotherapy; group B patients started WF during S-1 chemotherapy; and group C patients started WF after completing S-1 chemotherapy. Results A total of 21 patients with gastric cancer were included in the study; group A ( n = 8), group B ( n = 10) and group C ( n = 3). Seven patients (88%) in group A, seven (70%) in group B and all of the patients (100%) in group C had >2.5 PT-INR. There was no significant difference in the time-to-exceed 2.5 PT-INR between groups A and B. Conclusions These findings suggest that the timing of WF use in relation to S-1 chemotherapy might not be an important factor for PT-INR, although the low patient numbers included in the study should be taken into consideration. PMID- 27553807 TI - Telehealthcare for Chronic Obstructive Pulmonary Disease in Switzerland Is Feasible and Appreciated by Patients. AB - BACKGROUND: Earlier detection of acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) could reduce emergency admissions and hospitalisations. Studies investigating COPD management programs supported by telehealthcare (THC) have shown conflicting results. OBJECTIVES: To test the feasibility, safety and acceptance of THC for COPD. METHODS: Patients daily filled out an online questionnaire focused on the detection of AECOPD. The THC platform is integrated in a comprehensive electronic patient data repository, which has to be available for all patients in Switzerland by law by 2017. The study team called the patient by phone in case of suspected AECOPD. RESULTS: Of 339 screened patients, 14% were included. Main reasons for exclusion were missing technical equipment and unwillingness to participate in a study (50%). Data completeness was 88%; 94% completed the study. The current THC approach triggered 230 telephone calls, which led to the verification of 60 AECOPD in 22 patients. Three AECOPD were not detected. Sensitivity, specificity, positive and negative predictive value of the questionnaire-based THC approach in detecting AECOPD was 95, 98, 26 and 99.9%, respectively. Overall patient satisfaction in respect to their health condition improved significantly (VAS 8-8.7; p = 0.002). CONCLUSIONS: Adding THC to state of-the-art COPD management is feasible in a selected subgroup of patients. We estimate that up to 50% of COPD patients could be eligible for a THC strategy. Patient compliance, acceptance and satisfaction were very high. With the proposed approach, we missed only very few AECOPD events. However, a telephone-based verification of THC alerts was required. Overall, in this proof-of-concept study, we experienced a positive effort-to-benefit ratio. PMID- 27553808 TI - RNA-sequencing analysis reveals the hepatotoxic mechanism of perfluoroalkyl alternatives, HFPO2 and HFPO4, following exposure in mice. AB - The toxicological impact of traditional perfluoroalkyl chemicals has led to the elimination and restriction of these substances. However, many novel perfluoroalkyl alternatives remain unregulated and little is known about their potential effects on environmental and human health. Daily administration of two alternative perfluoroalkyl substances, HFPO2 and HFPO4 (1 mg kg-1 body weight), for 28 days resulted in hepatomegaly and hepatic histopathological injury in mice, particularly in the HFPO4 group. We generated and compared high-throughput RNA-sequencing data from hepatic tissues in control and treatment group mice to clarify the mechanism of HFPO2 and HFPO4 hepatotoxicity. We identified 146 (101 upregulated, 45 downregulated) and 1295 (716 upregulated, 579 downregulated) hepatic transcripts that exhibited statistically significant changes (fold change >=2 or <=0.5, false discovery rate < 0.05) after HFPO2 and HFPO4 treatment, respectively. Among them, 111 (82 upregulated, 29 downregulated) transcripts were changed in both groups, and lipid metabolism associated genes were dominant. Thus, similar to their popular predecessors, HFPO2 and HFPO4 exposure exerted hepatic effects, including hepatomegaly and injury, and altered lipid metabolism gene levels in the liver, though HFPO4 exerted greater hepatotoxicity than HFPO2. The unregulated use of these emerging perfluoroalkyl alternatives may affect environmental and human health, and their biological effects need further exploration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27553810 TI - Rhodium-Catalyzed Dehydrogenative Silylation of Acetophenone Derivatives: Formation of Silyl Enol Ethers versus Silyl Ethers. AB - A series of rhodium-NSiN complexes (NSiN=bis (pyridine-2-yloxy)methylsilyl fac coordinated) is reported, including the solid-state structures of [Rh(H)(Cl)(NSiN)(PCy3 )] (Cy=cyclohexane) and [Rh(H)(CF3 SO3 )(NSiN)(coe)] (coe=cis-cyclooctene). The [Rh(H)(CF3 SO3 )(NSiN)(coe)]-catalyzed reaction of acetophenone with silanes performed in an open system was studied. Interestingly, in most of the cases the formation of the corresponding silyl enol ether as major reaction product was observed. However, when the catalytic reactions were performed in closed systems, formation of the corresponding silyl ether was favored. Moreover, theoretical calculations on the reaction of [Rh(H)(CF3 SO3 )(NSiN)(coe)] with HSiMe3 and acetophenone showed that formation of the silyl enol ether is kinetically favored, while the silyl ether is the thermodynamic product. The dehydrogenative silylation entails heterolytic cleavage of the Si-H bond by a metal-ligand cooperative mechanism as the rate-determining step. Silyl transfer from a coordinated trimethylsilyltriflate molecule to the acetophenone followed by proton transfer from the activated acetophenone to the hydride ligand results in the formation of H2 and the corresponding silyl enol ether. PMID- 27553809 TI - Hematopoietic stem cells and solid organ transplantation. AB - Solid organ transplantation provides lifesaving therapy for patients with end stage organ disease. In order for the transplanted organ to survive, the recipient must take a lifelong cocktail of immunosuppressive medications that increase the risk for infections, malignancies and drug toxicities. Data from many animal studies have shown that recipients can be made tolerant of their transplanted organ by infusing stem cells, particularly hematopoietic stem cells, prior to the transplant. The animal data have been translated into humans and now several clinical trials have demonstrated that infusion of hematopoietic stem cells, along with specialized conditioning regimens, can permit solid organ allograft survival without immunosuppressive medications. This important therapeutic advance has been made possible by understanding the immunologic mechanisms by which stem cells modify the host immune system, although it must be cautioned that the conditioning regimens are often severe and associated with significant morbidity. This review discusses the role of hematopoietic stem cells in solid organ transplantation, provides an understanding of how these stem cells modify the host immune system and describes how newer information about adaptive and innate immunity might lead to improvements in the use of hematopoietic stem cells to induce tolerance to transplanted organs. PMID- 27553811 TI - Optimal Management of Leptomeningeal Carcinomatosis in Breast Cancer Patients-A Systematic Review. AB - The incidence of leptomeningeal carcinomatosis in breast cancer patients (LC-BC) is increasing. Despite significantly affecting patient quality of life (QoL) and overall survival (OS), little is known about its optimal management. A systematic review of treatment strategies for LC-BC was performed. EMBASE, Ovid Medline, Pubmed, and the Cochrane Central Register of Controlled Trials were searched from 1946 to 2015 for trials reporting on treatments for LC-BC. All treatment modalities and study types were considered. The outcome measures of interest included OS, time to neurologic progression (TTNP), QoL, and treatment toxicity. Of 718 unique citations, 173 studies met the prespecified eligibility criteria. Most were not specific to LC-BC patients. Of 4 identified randomized controlled trials (RCTs), 1 was specific to LC-BC patients and compared systemic therapy and involved-field radiotherapy with or without intrathecal (IT) methotrexate (35 patients), and the remaining 3 had compared different IT chemotherapy regimens (58 of 157 with LC-BC). Of the remaining studies, 19 were nonrandomized interventional studies (225 LC-BC patients), 148 were observational studies (3230 LC-BC patients), and 2 systematic reviews. Minimal prospective data were available on OS, TTNP, QoL, and toxicity. Owing to study heterogeneity, meta analyses of the endpoint data could not be performed. Limited high-quality evidence exists regarding optimal treatment of LC-BC. The identified studies were heterogeneous and often methodologically poor. The only RCT that specifically assessed the role of IT chemotherapy showed no benefit, and, if anything, harm. Further prospective, tumor-specific trials with improved interstudy methodologic consistency and transparently reported data on OS, TTNP, QoL, and toxicity are urgently needed. PMID- 27553812 TI - Micropropagation and genetic transformation of Tylophora indica (Burm. f.) Merr.: a review. AB - KEY MESSAGE: This review provides an in-depth and comprehensive overview of the in vitro culture of Tylophora species, which have medicinal properties. Tylophora indica (Burm. f.) Merr. is a climbing perennial vine with medicinal properties. The tissue culture and genetic transformation of T. indica, which has been extensively studied, is reviewed. Micropropagation using nodal explants has been reported in 25 % of all publications. Leaf explants from field-grown plants has been the explant of choice of independent research groups, which reported direct and callus-mediated organogenesis as well as callus-mediated somatic embryogenesis. Protoplast-mediated regeneration and callus-mediated shoot organogenesis has also been reported from stem explants, and to a lesser degree from root explants of micropropagated plants in vitro. Recent studies that used HPLC confirmed the potential of micropropagated plants to synthesize the major T. indica alkaloid tylophorine prior to and after transfer to field conditions. The genetic integrity of callus-regenerated plants was confirmed by RAPD in a few reports. Tissue culture is an essential base for genetic transformation studies. Hairy roots and transgenic T. indica plants have been shown to accumulate tylophorine suggesting that in vitro biology and transgenic methods are viable ways of clonally producing valuable germplasm and mass producing compounds of commercial value. Further studies that investigate the factors affecting the biosynthesis of Tylophora alkaloids and other secondary metabolites need to be conducted using non-transformed as well as transformed cell and organ cultures. PMID- 27553813 TI - More "how to lie with statistics" in the NHS. PMID- 27553814 TI - Hyaluronic acid-coated, prodrug-based nanostructured lipid carriers for enhanced pancreatic cancer therapy. AB - CONTEXT: Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over expressed receptors in various kinds of cancer cells. OBJECTIVE: The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs. METHODS: GEM stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model. RESULTS: HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model. CONCLUSION: It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers. PMID- 27553815 TI - Successful scleral buckling of late-onset visual decrease in eye with retinal folds. AB - PURPOSE: To describe the outcome of scleral buckling to treat radial retinal folds (RFs) that caused a late-onset and sudden visual decrease with impairment of the fovea. METHODS: This is an observational case report. Ophthalmic examinations were performed preoperatively and postoperatively and included measurement of the best-corrected visual acuity (BCVA), fundus examination, fluorescein angiography, focal macular electroretinography (FM-ERG), and spectral domain optical coherence tomography (OCT). RESULTS: A patient, whose case was reported previously, had a superonasal retinal detachment with a dislocated fovea and good BCVA in her right eye and a sustained BCVA of 40/50 by age 17 years and 3 months. The BCVA decreased suddenly to 20/200 at age 17 years and 11 months. Fundus examinations showed micro-dislocation of the fovea to the RFs and narrowing of the RFs compared with the previous report. FM-ERG showed an almost extinguished response, and OCT images showed abnormalities of the outer nuclear and photoreceptor layers. Encircling and radial scleral buckling was performed. Four months postoperatively, the BCVA improved to 30/50, which corresponded to the recovery of the FM-ERG response and findings on the OCT images. One year and 3 months postoperatively, the BCVA recovered to 35/50 with repositioning of the fovea. CONCLUSIONS: Simultaneous encircling and radial scleral buckling resulted in the recovery of both retinal function and structure in the current case and is a useful surgical option to treat late-onset progressive RFs due to intensification of traction. PMID- 27553816 TI - MY APPROACH to the diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D)*. PMID- 27553817 TI - MY APPROACH to the patient diagnosed with significant left main disease: Use of FFR, IVUS, and OCT. PMID- 27553818 TI - MY APPROACH to outpatients with suspected CAD. PMID- 27553819 TI - MY APPROACH to selecting patients for videoscopic cardiac sympathetic denervation (CSD)*. PMID- 27553820 TI - MY APPROACH to the use of CT in triage of chest pain in the ED. PMID- 27553821 TI - MY APPROACH to evaluating a patient with a serious illness*. PMID- 27553822 TI - Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory. AB - RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory. PMID- 27553823 TI - Sex differences in behavioral and PKA cascade responses to repeated cocaine administration. AB - Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats. PMID- 27553825 TI - Levofloxacin-induced transient musculospiral paralysis. PMID- 27553824 TI - Unstuck in time: episodic future thinking reduces delay discounting and cigarette smoking. AB - RATIONALE: Delay discounting, or the devaluation of delayed outcomes, appears to play an etiological role in tobacco and other substance-use disorders. OBJECTIVES: No human studies to our knowledge have been designed to examine whether experimental reductions in delay discounting produce concomitant reduction in drug use. METHODS: Using methods from prior studies on delay discounting and obesity, we examined the effects of episodic future thinking (EFT; a form of mental prospection) on delay discounting and cigarette self administration in smokers. RESULTS: Consistent with prior data, EFT significantly reduced both delay discounting (Cohen's d effect size = 0.65) and the number of cigarette puffs earned in a cigarette self-administration task (d = 0.58). CONCLUSIONS: The effects of EFT on delay discounting generalize to smokers; EFT also reduces laboratory-based cigarette self-administration. Potential mechanisms of EFT's effects are discussed as well as implications of EFT for clinical treatment of substance-use disorders. PMID- 27553826 TI - Positive fluid balance as a major predictor of clinical outcome of patients with sepsis/septic shock after ICU discharge. AB - INTRODUCTION: Sepsis and septic shock continue to be syndromes that carry a high mortality rate worldwide. Early aggressive fluid and vasopressor support have resulted in significant improvement in patient outcomes. The prognostic clinical significance of a positive fluid balance in septic intensive care unit (ICU) patients remains undetermined. METHODS: We collected data from 297 septic patients hospitalized in our general and medical ICUs at Soroka Medical Center between January 2005 and June 2011 and divided the 4 study groups into the following 4 fluid balances: group 1, patients with fluid balance at discharge from ICU (FBD) less than 10 L; group 2, patients with an FBD of 10 to 20 L; group 3, patients with an FBD of 20 to 30 L; and group 4, patients with FBD in excess of 30 L. RESULTS: The ICU and in-hospital mortality rate was also significantly higher in groups 2 to 4 as compared with group 1 (P < .001 for both ICU and in hospital mortality). The positive cumulative FBD was found to be an independent predictor of ICU mortality (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06; P < .001; Table 3) and in-hospital mortality (OR, 1.06; 95% CI, 1.03 1.08; P < .001; Table 5) and also to constitute a risk factor for new organ system dysfunction at hospital discharge (OR, 1.01; 95% CI, 1.01-1.013; P < .001; Table 6) in critically ill patients with severe sepsis/septic shock. CONCLUSIONS: Although it is a monocentric retrospective study, we suggest that positive cumulative fluid balance is one of the major factors that can predict the clinical outcome of critically ill patients during their ICU stay and after their discharge from the ICU. PMID- 27553827 TI - Treatment in carbon monoxide poisoning patients with headache: a prospective, multicenter, double-blind, controlled clinical trial. AB - BACKGROUND: There is a lack of specificity of the analgesic agents used to treat headache and underlying acute carbon monoxide poisoning. OBJECTIVE: To compare effectiveness of "oxygen alone" vs "metoclopramide plus oxygen" vs "metamizole plus oxygen" therapy in treating carbon monoxide-induced headache. DESIGN: A prospective, multicenter, double-blind, controlled trial. SETTING: Three emergency departments in Turkey. POPULATION: Adult carbon monoxide poisoning patients with headache. METHODS: A total of 117 carbon monoxide-intoxicated patients with headache were randomized into 3 groups and assessed at baseline, 30 minutes, 90 minutes, and 4 hours. MAIN OUTCOME MEASURE: The primary outcome was patient-reported improvement rates for headache. Secondary end points included nausea, need for rescue medication during treatment, and reduction in carboxyhemoglobin levels. RESULTS: During observation, there was no statistical difference between drug type and visual analog scale score change at 30 minutes, 90 minutes, or 4 hours, for either headache or nausea. No rescue medication was needed during the study period. The reduction in carboxyhemoglobin levels did not differ among the 3 groups. CONCLUSION: The use of "oxygen alone" is as efficacious as "oxygen plus metoclopramide" or "oxygen plus metamizole sodium" in the treatment of carbon monoxide-induced headache. PMID- 27553828 TI - Delayed traumatic splenic injury. PMID- 27553829 TI - Interventional lung assist and extracorporeal membrane oxygenation in a patient with near-fatal asthma. PMID- 27553830 TI - Measurement of superficial and deep abdominal muscle thickness: an ultrasonography study. AB - BACKGROUND: Real-time ultrasound imaging is a valid method in the field of rehabilitation. The ultrasound imaging allows direct visualization for real-time study of the muscles as they contract over the time. Measuring of the size of each abdominal muscle in relation to the others provides useful information about the differences in structure, as well as data on trunk muscle activation patterns. The purpose of this study was to assess the size and symmetry of the abdominal muscles at rest in healthy adults and to provide a reference range of absolute abdominal muscle size in a relatively large population. METHOD: A total 156 healthy subjects with the age range of 18-44 years were randomly recruited. The thickness of internal oblique, external oblique, transverse abdominis, and rectus abdominis muscles was measured at rest on both right and left sides using ultrasound. Independent t test was used to compare the mean thickness of each abdominal muscle between males and females. Differences on side-to-side thicknesses were assessed using paired t test. The association between abdominal muscle thicknesses with gender and anthropometric variables was examined using the Pearson correlation coefficient. RESULTS: A normal pattern of increasing order of mean abdominal muscle thickness was found in both genders at both right and left sides: transverse abdominis < external oblique < internal oblique < rectus abdominis. There was a significant difference on the size of transverse abdominis, internal oblique, and external oblique muscles between right and left sides in both genders. Males had significantly thicker abdominal muscles than females. Age was significantly correlated with the thickness of internal oblique, external oblique, and rectus abdominis muscles. Body mass index was also positively correlated with muscle thickness of rectus abdominis and external oblique. CONCLUSIONS: The results provide a normal reference range for the abdominal muscles in healthy subjects and may be used as an index to find out abnormalities and also to evaluate the effectiveness of different interventions. PMID- 27553831 TI - HHLA2, a New Immune Checkpoint Member of the B7 Family, Is Widely Expressed in Human Lung Cancer and Associated with EGFR Mutational Status. AB - PURPOSE: Immunotherapy with antibodies against B7/CD28 family members, including PD-1, PD-L1, and CTLA-4 has shifted the treatment paradigm for non-small cell lung carcinoma (NSCLC) with improved clinical outcome. HHLA2 is a newly discovered member of the family. By regulating T-cell function, HHLA2 could contribute to tumor immune suppression and thus be a novel target for cancer immunotherapy. There is limited information and critical need to characterize its expression profile and clinical significance in NSCLC. EXPERIMENTAL DESIGN: We performed IHC with an HHLA2-specific antibody (clone 566.1) using tissue microarrays constructed from 679 NSCLC tumor tissues, including 392 cases in the discovery set and 287 cases in the validation cohort. We also studied clinicopathologic characteristics of these patients. RESULTS: Overall, HHLA2 was not detected in most of normal lung tissue but expressed in 66% of NSCLC across different subtypes. In particular, EGFR-mutated NSCLC was significantly associated with higher tumor HHLA2 expression in both discovery (EGFR vs. WT: 76% vs. 53%, P = 0.01) and validation cohorts (89% vs. 69%, P = 0.01). In one of the two cohorts, HHLA2 expression was higher in lung adenocarcinoma as compared with squamous and large cell histology, non-Hispanic White versus Hispanics, and tumors with high tumor-infiltrating lymphocyte (TIL) density. In the multivariate analysis, EGFR mutation status and high TIL intensity were independently associated with HHLA2 expression in lung adenocarcinoma. CONCLUSIONS: HHLA2 is widely expressed in NSCLC and is associated with EGFR mutation and high TILs in lung adenocarcinoma. It is potentially a novel target for lung cancer immunotherapy. Clin Cancer Res; 23(3); 825-32. (c)2016 AACR. PMID- 27553832 TI - PI3K-mTOR Pathway Inhibition Exhibits Efficacy Against High-grade Glioma in Clinically Relevant Mouse Models. AB - Purpose: The PI3K-AKT-mTOR signaling pathway is frequently activated in glioblastoma and offers several druggable targets. However, clinical efficacy of PI3K/mTOR inhibitors in glioblastoma has not yet been demonstrated. Insufficient drug delivery may limit the efficacy of PI3K/mTOR inhibitors against glioblastoma. The presence of the efflux transporters ABCB1/Abcb1 (P glycoprotein, MDR1) and ABCG2/Abcg2 (BCRP) at the blood-brain barrier (BBB) restricts the brain penetration of many drugs.Experimental Design: We used in vitro drug transport assays and performed pharmacokinetic/pharmacodynamic studies in wild-type and ABC-transporter knockout mice. The efficacy of PI3K-mTOR inhibition was established using orthotopic allograft and genetically engineered spontaneous glioblastoma mouse models.Results: The mTOR inhibitors rapamycin and AZD8055 are substrates of ABCB1, whereas the dual PI3K/mTOR inhibitor NVP-BEZ235 and the PI3K inhibitor ZSTK474 are not. Moreover, ABCG2 transports NVP-BEZ235 and AZD8055, but not ZSTK474 or rapamycin. Concordantly, Abcb1a/b-/-;Abcg2-/- mice revealed increased brain penetration of rapamycin (13-fold), AZD8055 (7.7-fold), and NVP-BEZ235 (4.5-fold), but not ZSTK474 relative to WT mice. Importantly, ABC transporters limited rapamycin brain penetration to subtherapeutic levels, while the reduction in NVP-BEZ235 brain penetration did not prevent target inhibition. NVP-BEZ235 and ZSTK474 demonstrated antitumor efficacy with improved survival against U87 orthotopic gliomas, although the effect of ZSTK474 was more pronounced. Finally, ZSTK474 prolonged overall survival in Cre-LoxP conditional transgenic Pten;p16Ink4a/p19Arf;K-Rasv12;LucR mice, mainly by delaying tumor onset.Conclusions: PI3K/mTOR inhibitors with weak affinities for ABC transporters can achieve target inhibition in brain (tumors), but have modest single-agent efficacy and combinations with (BBB penetrable) inhibitors of other activated pathways may be required. Clin Cancer Res; 23(5); 1286-98. (c)2016 AACR. PMID- 27553833 TI - Exportin-5 Functions as an Oncogene and a Potential Therapeutic Target in Colorectal Cancer. AB - Purpose: Dysregulated expression of miRNAs has emerged as a hallmark feature in human cancers. Exportin-5 (XPO5), a karyopherin family member, is a key protein responsible for transporting precursor miRNAs from the nucleus to the cytoplasm. Although XPO5 is one of the key regulators of miRNA biogenesis, its functional role and potential clinical significance in colorectal cancer remains unclear.Experimental Design: The expression levels of XPO5 were initially assessed in three genomic datasets, followed by determination and validation of the relationship between XPO5 expression and clinicopathologic features in two independent colorectal cancer patient cohorts. A functional characterization of XPO5 in colorectal cancer was examined by targeted gene silencing in colorectal cancer cell lines and a xenograft animal model.Results: XPO5 is upregulated, both at mRNA and protein levels, in colorectal cancers compared with normal tissues. High XPO5 expression is associated with worse clinicopathologic features and poor survival in colorectal cancer patient cohorts. The siRNA knockdown of XPO5 resulted in reduced cellular proliferation, attenuated invasion, induction of G1 S cell-cycle arrest, and downregulation of key oncogenic miRNAs in colorectal cancer cells. These findings were confirmed in a xenograft animal model, wherein silencing of XPO5 resulted in the attenuation of tumor growth.Conclusions: XPO5 acts like an oncogene in colorectal cancer by regulating the expression of miRNAs and may be a potential therapeutic target in colorectal cancer. Clin Cancer Res; 23(5); 1312-22. (c)2016 AACR. PMID- 27553835 TI - Fat pads adjacent to tendinopathy: more than a coincidence? PMID- 27553836 TI - Identifying concussion: when guidelines collide with real-world implementation-is a formal medical diagnosis necessary in every case once a proper protocol is implemented? PMID- 27553837 TI - Long-term outcomes of resection in patients with symptomatic benign liver tumours. AB - BACKGROUND: Benign liver tumours (e.g., hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH), and haemangioma) are occasionally resected for alleged symptoms, although data on long-term outcomes is lacking. The aim of this cross sectional study was to assess long-term outcomes of surgical intervention. METHODS: Forty patients with benign tumours (HCA 20, FNH 12, giant haemangioma 4, cysts 4) were included. Patients filled in Validated McGill Pain Questionnaires, preoperatively and after a median of 54 months after resection. Outcomes were evaluated using paired sample t-test and (M) ANOVA. RESULTS: Relief of symptoms sustained in 30/40 patients, within a follow-up of 54 (24-148) months after resection. VAS scores were reduced from 5.5 preoperatively to 1.6 postoperatively (p < 0.001). Patients with left-sided tumours had higher postoperative Pain Rating Index (PRI), compared to patients with right-sided tumours: 15.3 vs. 5.8 (p = 0.018). If patients could reconsider undergoing surgery, 34/38 would again choose resection. Discomfort at the operative scar was the most common complaint: 8/40 patients, all after open surgery, of whom 3/40 had an incisional hernia. 7/40 patients had a laparoscopic resection. CONCLUSION: Resection relieved symptoms in 30/40 patients. The operative scar was a frequent source for remaining postoperative complaints, suggesting an advantage for a laparoscopic approach when feasible. PMID- 27553838 TI - A systematic review of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the body and tail of the pancreas. AB - BACKGROUND: To assess the published evidence on clinical outcomes following radical antegrade modular pancreatosplenectomy (RAMPS) for adenocarcinoma in the body or tail of the pancreas. METHOD: PubMed and Chinese Biomedical Literature databases were searched. The results of comparisons between RAMPS and standard retrograde pancreatosplenectomy (SRPS) were analyzed by meta-analytical techniques. RESULTS: The literature search identified 13 observational studies involving 354 patients undergoing RAMPS. The overall morbidity and 30-day mortality was 40% and 0% respectively. The R0 resection rate was 88%; the median number of retrieved lymph nodes was 21; and the median 5-year overall survival rate was 37%. The result of meta-analysis showed that RAMPS was associated with a significantly less intraoperative bleeding [weighted mean difference -195.2 (95% confidence interval (CI) -223.27 to -167.13); P < 0.001], a greater number of retrieved lymph nodes [odds ratio (OR) 6.19 (95% CI 3.72 to 8.67); P < 0.001] and a higher percentage of R0 resection [OR 2.46 (95% CI 1.13 to 5.35); P = 0.02] as compared with SRPS. CONCLUSION: The current literature provides supportive evidence that RAMPS is a safe and effective procedure for adenocarcinoma in the body or tail of the pancreas, and is oncologically superior to SRPS. PMID- 27553840 TI - Intracellular, biofilm-inhibitory and membrane-damaging activities of nimbolide isolated from Azadirachta indica A. Juss (Meliaceae) against meticillin-resistant Staphylococcus aureus. AB - Staphylococcus aureus is a leading aetiologic agent of nosocomial- and community acquired infectious diseases worldwide. The public health concern regarding staphylococcal infections is inflated by the increasing occurrence of multidrug resistant strains, e.g. multidrug- and meticillin-resistant S.aureus (MDR MRSA). This study was designed to evaluate the intracellular killing, membrane-damaging and biofilm-inhibitory activities of nimbolide isolated from Azadirachta indica against MDR MRSA. In vitro antibacterial activity of nimbolide was determined by performing MIC, minimal bactericidal concentration (MBC) and time-kill kinetic studies. Bacterial membrane-damaging activity was determined by membrane perturbation and scanning electron microscopy (SEM) examination. Biofilm inhibitory activities were determined by SEM. Cellular drug accumulation and assessments of intracellular activities were performed using Vero cell culture. SEM revealed that nimbolide caused significant membrane damage and lysis of the S. aureus cells. The biofilm structure was disrupted, and the biofilm formation was greatly reduced in the presence of nimbolide as examined by SEM. The level of accumulation of nimbolide in Vero cells incubated for 24 h is relatively higher than that of ciprofloxacin and nalidixic acid (Cc/Ce for nimbolide > ciprofloxacin and nalidixic acid). The viable number of intracellular S. aureus was decreased [reduction of ~2 log10 c.f.u. (mg Vero cell protein)-1] in a time dependent manner in the presence of nimbolide (4* MBC) that was comparable to that of tetracycline and nalidixic acid. The significant intracellular, biofilm inhibitory and bacterial membrane-damaging activities of nimbolide demonstrated here suggested that it has potential as an effective antibacterial agent for the treatment of severe infections caused by MDR MRSA. PMID- 27553841 TI - Recombinant Factor VIIa-Mediated Activation of Prothrombin Complex Concentrates. AB - Recombinant factor VIIa (rFVIIa) is used in the management of bleeding in patients with hemophilia. A generic biosimilar version of NovoSeven is also developed (AryoSeven). To compare the activation profile of NovoSeven and AryoSeven, 2 commercially available protein complex concentrates (PCCs) were used. Profilnine activated by RecombiPlasTin 2G resulted in conversions of prothrombin to prethrombin and thrombin at 5 to 30 minutes. However, addition of rFVIIa at final concentration range of 0.25 to 0.5 ug/mL to the same mixture resulted in total conversion of prothrombin to thrombin with a doublet at 36 kDa. Recombinant factor VIIa alone did not generate thrombin in native Beriplex, and the addition of rFVIIa to Beriplex failed to generate thrombin. Beriplex activated by RecombiPlasTin 2G resulted in complete conversion of prothrombin to thrombin. Both NovoSeven and AryoSeven exhibited similar activation profiles. These studies indicate that the activation of PCCs by both rFVIIa preparations results in comparable generation of thrombin. PMID- 27553839 TI - Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review. AB - Implementing the most suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ among second generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory. Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride, and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic treatment for a lengthy period of time. PMID- 27553843 TI - The relationship between self-reported habitual exercise and visual field defect progression: a retrospective cohort study. AB - BACKGROUND: Exercise reduces intraocular pressure (IOP) in the short term. However, it is not known whether exercise contributes to slower glaucomatous visual field defect progression. METHODS: Twenty-four primary open-angle glaucoma or exfoliation glaucoma patients who were evaluated by the Humphrey Field Analyzer (HFA) 24-2 program >= four times in 3 years were enrolled. Patients with a history of intraocular surgery in past 3 years or other eye diseases threatening visual fields were excluded. Patients were classified into two groups whether they had exercise habits or not. RESULTS: Eleven patients had exercise habits. The mean +/- standard error of IOP and MD slope were 14.8 +/- 0.9 mmHg and +0.20 +/- 0.20 dB/year in the exercise group and 13.3 +/- 0.8 mmHg and -0.53 +/- 0.18 dB/year in the non-exercise group (P = 0.24 and P = 0.01, respectively). Higher IOP [odds ratio (OR) = 0.44/1 mmHg increase; P = 0.02] and habitual exercise (OR = 0.04; P = 0.02) reduced the visual field defect progression risk in logistic regression analyses. CONCLUSIONS: Patients with self-reported exercise habits had slower glaucoma progression. PMID- 27553845 TI - Flow reversal bypass surgery: a treatment option for giant serpentine and dolichoectatic aneurysms-internal maxillary artery bypass with an interposed radial artery graft followed by parent artery occlusion. AB - Giant serpentine and dolichoectatic aneurysms (GSDAs) are a small subgroup of intracranial aneurysms that often have poor clinical outcomes and are hardly to be treated by either conservative or endovascular management. We assessed seven patients who underwent internal maxillary artery bypass using radial artery graft interposition followed by parent artery occlusion to treat GSDAs. Intraoperative Doppler ultrasonography was used to assess the patency of the graft. CT angiogram or DSA were used postoperatively. The patients received follow-up after discharge and their neurological outcomes were measured using the Glasgow Outcome Score. Postoperative angiogram demonstrated that all the grafted conduits were patent, and the aneurysms were absent in two and collapsed or shrank in five of the patients. The rate of normal life or independent daily activities after internal maxillary artery bypass in the anterior and posterior GSDA patients was 66.7 and 75 %, respectively. One patient experienced postoperative frontal ischemia and was managed conservatively. His symptoms had completely resolved at discharge. No patient encountered perforator's occlusion in the series. During 2.6 years follow up, six patients experienced favorable outcomes. One patient died in the third year after discharge attribute to unrelated disease. Based on the mechanism of flow reversal, internal maxillary artery bypass with radial artery graft followed by patent artery occlusion is an effective, minimally invasive treatment modality for select patients with GSDAs. PMID- 27553844 TI - New insights into the heterogeneity of Th17 subsets contributing to HIV-1 persistence during antiretroviral therapy. AB - BACKGROUND: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown. RESULTS: Here, we performed an in-depth transcriptional and functional characterization of four distinct Th17 subsets and investigated their contribution to HIV reservoir persistence during ART. In addition to the previously characterized CCR6(+)CCR4(+) (Th17) and CCR6(+)CXCR3(+) (Th1Th17) subsets, we reveal the existence of two novel CCR6(+) subsets, lacking (double negative, CCR6(+)DN) or co-expressing CXCR3 and CCR4 (double positive, CCR6(+)DP). The four subsets shared multiple Th17-polarization markers, a fraction of cells proliferated in response to C. albicans, and exhibited lineage commitment and plasticity when cultured under Th17 and Th1 conditions, respectively. Of note, fractions of CCR6(+)DN and Th17 demonstrated stable Th17-lineage commitment under Th1 polarization conditions. Among the four subsets, CCR6(+)DN expressed a unique transcriptional signature indicative of early Th17 development (IL-17F, STAT3), lymph-node homing (CCR7, CD62L), follicular help (CXCR5, BCL6, ASCL2), and self renewal (LEFI, MYC, TERC). Cross sectional and longitudinal studies demonstrated that CCR6(+)DN cells were the most predominant CCR6(+) subset in the blood before and after ART initiation; high frequencies of these cells were similarly observed in inguinal lymph nodes of individuals receiving long-term ART. Importantly, replication competent HIV was isolated from CCR6(+)DN of ART-treated individuals. CONCLUSIONS: Together, these results provide new insights into the functional heterogeneity of Th17-polarized CCR6(+)CD4(+) T-cells and support the major contribution of CCR6(+)DN cells to HIV persistence during ART. PMID- 27553846 TI - Characteristics and surgical strategies for posterior clinoid process meningioma: two case reports and review of the literature. AB - Clinical and radiological features or characteristics of posterior clinoid process (PCP) meningiomas have rarely been described because of their extreme scarcity and terminological confusion. Therefore, the strategies in the surgical intervention for PCP meningiomas have not been well established. Moreover, the presence of deep and critical neuroanatomical structures and relatively high morbidity, which can be difficult to predict preoperatively, make their surgical excision more challenging. We report two surgical cases of PCP meningioma and discuss the appropriate assessment of preoperative features and surgical strategies with review of the literature. Our study suggests that PCP meningioma may be characterized by the anterior displacement of internal carotid artery, and infero-laterally shifted posterior communicating arteries, and homonymous hemianopsia, a distinctive clinical feature. One of the key issues in PCP meningioma surgery is preservation of the optic nerve. Unlocking the optic nerve by anterior clinoidectomy and dissection, the falciform ligament is the important step to preserve vision for larger tumors. Complication with the perforators is also hazardous of these challenging surgeries than anterior clinoid meningiomas for their specific neuroanatomical structures and might not be feasible to avoid even with additional techniques and critical monitoring. A combination and multi staged-surgical approach can be options of tailor-made surgical strategy in cases with tumor adhesion to the perforators. PMID- 27553847 TI - A method for developing biomechanical response corridors based on principal component analysis. AB - The standard method for specifying target responses for human surrogates, such as crash test dummies and human computational models, involves developing a corridor based on the distribution of a set of empirical mechanical responses. These responses are commonly normalized to account for the effects of subject body shape, size, and mass on impact response. Limitations of this method arise from the normalization techniques, which are based on the assumptions that human geometry linearly scales with size and in some cases, on simple mechanical models. To address these limitations, a new method was developed for corridor generation that applies principal component (PC) analysis to align response histories. Rather than use normalization techniques to account for the effects of subject size on impact response, linear regression models are used to model the relationship between PC features and subject characteristics. Corridors are generated using Monte Carlo simulation based on estimated distributions of PC features for each PC. This method is applied to pelvis impact force data from a recent series of lateral impact tests to develop corridor bounds for a group of signals associated with a particular subject size. Comparing to the two most common methods for response normalization, the corridors generated by the new method are narrower and better retain the features in signals that are related to subject size and body shape. PMID- 27553848 TI - Smoothing spline analysis of variance models: A new tool for the analysis of cyclic biomechanical data. AB - Cyclic biomechanical data are commonplace in orthopedic, rehabilitation, and sports research, where the goal is to understand and compare biomechanical differences between experimental conditions and/or subject populations. A common approach to analyzing cyclic biomechanical data involves averaging the biomechanical signals across cycle replications, and then comparing mean differences at specific points of the cycle. This pointwise analysis approach ignores the functional nature of the data, which can hinder one's ability to find subtle differences between experimental conditions and/or subject populations. To overcome this limitation, we propose using mixed-effects smoothing spline analysis of variance (SSANOVA) to analyze differences in cyclic biomechanical data. The SSANOVA framework makes it possible to decompose the estimated function into the portion that is common across groups (i.e., the average cycle, AC) and the portion that differs across groups (i.e., the contrast cycle, CC). By partitioning the signal in such a manner, we can obtain estimates of the CC differences (CCDs), which are the functions directly describing group differences in the cyclic biomechanical data. Using both simulated and experimental data, we illustrate the benefits of using SSANOVA models to analyze differences in noisy biomechanical (gait) signals collected from multiple locations (joints) of subjects participating in different experimental conditions. Using Bayesian confidence intervals, the SSANOVA results can be used in clinical and research settings to reliably quantify biomechanical differences between experimental conditions and/or subject populations. PMID- 27553849 TI - The functional roles of muscles during sloped walking. AB - Sloped walking is biomechanically different from level-ground walking, as evidenced by changes in joint kinematics and kinetics. However, the changes in muscle functional roles underlying these altered movement patterns have not been established. In this study, we developed a total of 273 muscle-actuated simulations to assess muscle functional roles, quantified by induced body center of-mass accelerations and trunk and leg power, during walking on slopes of 0 degrees , +/-3 degrees , +/-6 degrees , and +/-9 degrees at 1.25m/s. The soleus and gastrocnemius both provided greater forward acceleration of the body parallel to the slope at +9 degrees compared to level ground (+126% and +66%, respectively). However, while the power delivered to the trunk by the soleus varied with slope, the magnitude of net power delivered to the trunk and ipsilateral leg by the biarticular gastrocnemius was similar across all slopes. At +9 degrees , the hip extensors absorbed more power from the trunk (230% hamstrings, 140% gluteus maximus) and generated more power to both legs (200% hamstrings, 160% gluteus maximus) compared to level ground. At -9 degrees , the knee extensors (rectus femoris and vasti) accelerated the body upward perpendicular to the slope at least 50% more and backward parallel to the slope twice as much as on level ground. In addition, the knee extensors absorbed greater amounts of power from the ipsilateral leg on greater declines to control descent. Future studies can use these results to develop targeted rehabilitation programs and assistive devices aimed at restoring sloped walking ability in impaired populations. PMID- 27553850 TI - Magnetically Alignable Bicelles with Unprecedented Stability Using Tunable Surfactants Derived from Cholic Acid. AB - Five novel surfactants were prepared by modifying the three hydroxy groups of sodium cholate with triethylene glycol chains endcapped with an amide (SC-C1 , SC n C4 , and SC-n C5 ) or a carbamoyl group (SC-On C4 and SC-Ot C4 ). The phase behavior of aqueous mixtures of these surfactants with 1,2-dimyristoyl-sn-glycero 3-phosphatidylcholine (DMPC) was systematically studied by 31 P NMR spectroscopy. The surfactants endcapped with carbamate groups (SC-On C4 and SC-Ot C4 ) formed magnetically alignable bicelles over unprecedentedly wide ranges of conditions, in terms of temperature (from 21-23 to >90 degrees C), lipid/surfactant ratio (from 5 to 8), total lipid content (5-20 wt %), and lipid type [DMPC, 1,2 dilauroyl-sn-glycero-3-phosphatidylcholine (DLPC), or 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC)]. In conjunction with appropriate phospholipids, the carbamate-endcapped surfactants afforded unique bicelles, characterized by exceptional thermal stabilities (from 0 to >90 degrees C), biomimetic lipid compositions (DMPC/POPC=25:75 to 50:50), and extremely large 2 H quadrupole splittings (up to 71 Hz). PMID- 27553851 TI - High-throughput fermentation screening for the yeast Yarrowia lipolytica with real-time monitoring of biomass and lipid production. AB - BACKGROUND: Because the model yeast Yarrowia lipolytica can synthesize and store lipids in quantities up to 20 % of its dry weight, it is a promising microorganism for oil production at an industrial scale. Typically, optimization of the lipid production process is performed in the laboratory and later scaled up for industrial production. However, the scale-up process can be complicated by genetic modifications that are optimized for one set of growing conditions can confer a less-than-optimal phenotype in a different environment. To address this issue, small cultivation systems have been developed that mimic the conditions in benchtop bioreactors. In this work, we used one such microbioreactor system, the BioLector, to develop high-throughput fermentation procedures that optimize growth and lipid accumulation in Y. lipolytica. Using this system, we were able to monitor lipid and biomass production in real time throughout the culture duration. RESULTS: The BioLector can monitor the growth of Y. lipolytica in real time by evaluating scattered light; this produced accurate measurements until cultures reached an equivalent of OD600nm = 115 and a cell dry weight of 100 g L( 1). In addition, a lipid-specific fluorescent probe was applied which reliably monitored lipid production up to a concentration of 12 g L(-1). Through screening various growing conditions, we determined that a carbon/nitrogen ratio of 35 was the most efficient for lipid production. Further screening showed that ammonium chloride and glycerol were the most valuable nitrogen and carbon sources, respectively, for growth and lipid production. Moreover, a carbon concentration above 1 M appeared to impair growth and lipid accumulation. Finally, we used these optimized conditions to screen engineered strains of Y. lipolytica with high lipid-accumulation capability. The growth and lipid content of the strains cultivated in the BioLector were compared to those grown in benchtop bioreactors. CONCLUSION: To our knowledge, this is the first time that the BioLector has been used to track lipid production in real time and to monitor the growth of Y. lipolytica. The present study also showed the efficacy of the BioLector in screening growing conditions and engineered strains prior to scale-up. The method described here could be applied to other oleaginous microorganisms. PMID- 27553853 TI - A researcher's guide to mass spectrometry-based proteomics. AB - Mass spectrometry (MS) is widely recognized as a powerful analytical tool for molecular research. MS is used by researchers around the globe to identify, quantify, and characterize biomolecules like proteins from any number of biological conditions or sample types. As instrumentation has advanced, and with the coupling of liquid chromatography (LC) for high-throughput LC-MS/MS, a proteomics experiment measuring hundreds to thousands of proteins/protein groups is now commonplace. While expert practitioners who best understand the operation of LC-MS systems tend to have strong backgrounds in physics and engineering, consumers of proteomics data and technology are not exposed to the physio chemical principles underlying the information they seek. Since articles and reviews tend not to focus on bridging this divide, our goal here is to span this gap and translate MS ion physics into language intuitive to the general reader active in basic or applied biomedical research. Here, we visually describe what happens to ions as they enter and move around inside a mass spectrometer. We describe basic MS principles, including electric current, ion optics, ion traps, quadrupole mass filters, and Orbitrap FT-analyzers. PMID- 27553852 TI - Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model. AB - BACKGROUND: A newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains unsettled. Herein, we reveal the effects of O. formosana in ameliorating hyperglycemia accompanied with depression. METHODS: Diabetes was induced in mice by employing streptozotocin(STZ), a chemical that is toxic to insulin-producing beta cells of the pancreas. These streptozotocin (STZ) induced diabetic mice showed combined symptoms of hyperglycemia and depressive behaviors. Twenty-four STZ-induced mice were randomly divided into 3 groups subjected to oral gavage with 100 MUL solution of either PBS or 25 mg/mL Ophiocordyceps formosana extract (OFE) or 2 mg/mL rosiglitazone (Rosi, positive control group). Treatments were administered once per day for 28 days. An additional 6 mice without STZ induction were treated with PBS to serve as the control group. Insulin sensitivity was measured by a glucose tolerance test and levels of adiponectin in plasma and adipose tissue were also quantified. Behavioral tests were conducted and levels of monoamines in various brain regions relating to depression were evaluated. RESULTS: HPLC analysis uncovered three major constituents, adenosine, D-mannitol and cordycepin, within O. formosana similar to other prestigious medicinal Cordyceps spp.. STZ-induced diabetic mice demonstrated decreased body weight and subcutaneous adipose tissue, while these symptoms were recovered in mice receiving OFE treatment. Moreover, the OFE group displayed improved insulin sensitivity and elevated adiponectin within the plasma and adipose tissue. The anti-depressive effect of OFE was observed in various depression-related behavior tests. Concurrently, neurotransmitters, like 5-HT and dopamine in the frontal cortex, striatum and hippocampus were found to be up regulated in OFE-treated mice. CONCLUSIONS: Our findings illustrated, for the first time, the medicinal merits of O. formosana on Type I diabetes and hyperglycemia-induced depression. OFE were found to promote the expression of adiponectin, which is an adipokine involved in insulin sensitivity and hold anti depressive effects. In addition, OFE administration also displayed altered levels of neurotransmitters in certain brain regions that may have contributed to its anti-depressive effect. Collectively, this current study provided insights to the potential therapeutic effects of O. formosana extracts in regards to hyperglycemia and its depressive complications. PMID- 27553854 TI - LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3 mediated Sox4 expression. AB - Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self renewal. PMID- 27553855 TI - In silico identification of lysocin biosynthetic gene cluster from Lysobacter sp. RH2180-5. PMID- 27553856 TI - Remnant lipoprotein size distribution profiling via dynamic light scattering analysis. AB - BACKGROUND: Remnant lipoproteins (RLP) are a metabolically derived subpopulation of triglyceride-rich lipoproteins (TRL) in human blood that are involved in the metabolism of dietary fats or triglycerides. RLP, the smaller and denser variants of TRL particles, are strongly correlated with cardiovascular disease (CVD) and were listed as an emerging atherogenic risk factor by the AHA in 2001. METHODS: Varying analytical techniques used in clinical studies in the size determination of RLP contribute to conflicting hypotheses in regard to whether larger or smaller RLP particles contribute to CVD progression, though multiple pathways may exist. RESULTS: We demonstrated a unique combinatorial bioanalytical approach involving the preparative immunoseparation of RLP, and dynamic light scattering for size distribution analysis. CONCLUSIONS: This is a new facile and robust methodology for the size distribution analysis of RLP that in conjunction with clinical studies may reveal the mechanisms by which RLP cause CVD progression. PMID- 27553857 TI - Smartphone monitoring of pneumatic tube system-induced sample hemolysis. AB - BACKGROUND: Pneumatic tube systems (PTSs) are convenient methods of patient sample transport in medical centers, but excessive acceleration force and time/distance traveled in the PTS have been correlated with increased blood sample hemolysis. We investigated the utility of smartphones for monitoring of PTS-related variables. METHODS: Smartphones were sent through the PTS from several hospital locations. Each smartphone used 2 apps as data-loggers to record force of acceleration vs time. To relate the smartphone data to sample integrity, blood samples were collected from 5 volunteers, and hemolysis of the samples was analyzed after they were transported by hand or via 1 of 2 PTS routes. Increased sample hemolysis as measured by plasma lactate dehydrogenase (LD) was also related to the amount of transport in the PTS. RESULTS: The smartphones showed higher duration of forceful acceleration during transport through 1 of the 2 PTS routes, and the increased duration correlated with significant increases in hemolysis (H)-index and plasma LD. In addition, plasma LD showed a positive linear relationship with number of shock forces experienced during transport through the PTS. CONCLUSIONS: Smartphones can monitor PTS variables that cause sample hemolysis. This provides an accessible method for investigating specific PTS routes in medical centers. PMID- 27553858 TI - Serum pentraxin 3 is elevated in patients with neurological Wilson's disease. AB - BACKGROUND: Wilson's disease (WD) is an autosomal recessive inherited disorder of copper (Cu) metabolism, resulting in pathological accumulation of Cu in many organs and tissues, predominantly in the liver and brain. Cu deposition may lead to neuroinflammation in the brain of WD patients. Pentraxin 3 (PTX3) may play an important role in innate immunity and in WD. We compared plasma PTX3 concentrations in WD patients and healthy controls, and to determine whether PTX3 concentration was associated with neurological disease severity. METHODS: This study included 86 WD patients and 28 controls. Plasma PTX3 and C-reactive protein (CRP) concentration levels were measured using specific enzyme-linked immunosorbent assays. Disease severity was determined using the neurological Global Assessment Scale (GAS) for WD. RESULTS: Plasma PTX3 levels were significantly higher in patients with neurological WD than in controls. PTX3 levels in WD patients were associated with neurological disease severity. However, there was no correlation between CRP and neurological GAS scores. CONCLUSIONS: PTX3 represents a potential biochemical marker of disease severity in patients with neurological WD. PMID- 27553859 TI - Outcomes associated with fetal hepatobiliary cysts: systematic review and meta analysis. AB - OBJECTIVE: To explore the outcomes associated with fetal hepatobiliary cysts. METHODS: MEDLINE and EMBASE were searched for studies reporting on outcomes of fetal hepatobiliary cysts. Outcomes observed were resolution/reduction and increase in cyst size, associated congenital anomalies of the biliary tract and liver, abnormal postnatal liver function tests, clinical symptoms, need for surgery, postsurgical complications and predictive accuracy of prenatal ultrasound in identifying correctly hepatobiliary cysts. Meta-analysis of proportions was used to analyze the data. RESULTS: The search identified 1498 articles, and 22 studies (252 fetuses) were included in the systematic review. For fetal hepatic cysts, resolution or reduction in cyst size either pre- or postnatally occurred in 59.3% (95% CI, 30.9-84.7%) of cases, while an increase in cyst size occurred in 8.7% (95% CI, 1.1-22.4%). No case of hepatic cyst had associated malformations of the biliary tract at birth. Clinical symptoms occurred in 14.8% (95% CI, 6.3-26.1%) of cases and, in 5.4% (95% CI, 0.9-13.6%), they were related to the presence of bile obstruction due to compression of the cyst on the biliary tract. No case of hepatic cyst had abnormal liver function at birth. For fetal biliary cysts, resolution or reduction in cyst size occurred in 8.7% (95% CI, 2.7-17.5%) of cases and an increase in size occurred in 34.4% (95% CI, 20.5-49.8%). Congenital anomalies of the biliary tract and liver, such as fibrosis, occurred in 21.5% (95% CI, 10.2-35.6%) and 17.4% (95% CI, 5.4-34.4%) of cases, respectively. 57.3% (95% CI, 33.9-79.0%) of cases showed impairment in liver function after birth, while 55.0% (95% CI, 37.5-71.9%) showed clinical symptoms, mainly due to bile obstruction (47.9% (95% CI, 29.4-66.7%)). Postsurgical complications occurred in 10.9% (95% CI, 3.7-21.3%) of operated cases. Risk assessment according to different cut-offs of cyst size could not be performed in view of the very small number of included studies. CONCLUSIONS: Fetal hepatic cysts are benign, with a low likelihood of associated anomalies of the hepatobiliary tract, abnormal liver function or clinical symptoms. Congenital biliary cysts are associated with a high rate of progression, abnormal liver function after birth and clinical symptoms. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27553860 TI - Erratum to: In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1. PMID- 27553861 TI - Heat shock protein 90 is essential for replication of porcine circovirus type 2 in PK-15 cells. AB - Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated disease (PCVAD). However, the mechanism of PCV2 replication has not been understood completely. Heat shock protein 90 (Hsp90) plays an important role in viral genome replication, viral genes expression, and viral particle packaging. In this study, we firstly found that inhibition of Hsp90 by pretreatment of host cells with 17-AAG, a specific inhibitor of Hsp90, or blocking Hsp90alpha/Hsp90beta with siRNA, resulted in significantly reduced viral replication in PK-15 cells. But inhibition of Hsp90 by 17-AAG did not affect PCV2 entry into the host cells. Meanwhile, over-expression of Hsp90alpha/Hsp90beta enhanced PCV2 genome replication and virion production. In addition, Hsp90beta was enriched in the nuclear zone in the cells infected with PCV2. But it did not interact with the viral Cap/Rep proteins. It suggested that Hsp90 is required for PCV2 production in PK-15 cells culture. It should be helpful for further evaluating the mechanism of replication and pathogenesis of PCV2 and developing novel antiviral therapies. PMID- 27553863 TI - Reply. PMID- 27553862 TI - miR-29a differentially regulates cell survival in astrocytes from cornu ammonis 1 and dentate gyrus by targeting VDAC1. AB - Neurons in the cornu ammonis 1 (CA1) region of the hippocampus are vulnerable to cerebral ischemia, while dentate gyrus (DG) neurons are more resistant. This effect is mediated by local astrocytes, and may reflect differences in subregional hippocampal expression of miR-29a. We investigated the role of miR 29a on survival of hippocampal astrocytes cultured selectively from CA1 and DG in response to glucose deprivation (GD). CA1 astrocytes exhibited more cell death and a greater decrease in miR-29a than DG astrocytes. A reciprocal change was observed in the mitochondrial voltage dependent cation channel-1 (VDAC1), a regulator of mitochondria and target of miR-29a. In CA1 astrocytes, increasing miR-29a decreased VDAC1 and improved cell survival, while knockdown of VDAC1 improved survival. Finally, the protective effect of miR-29a was eliminated by inhibition of miR-29a/VDAC1 binding. These findings suggest that the selective vulnerability of the CA1 to injury may be due in part to a limited miR-29a response in CA1 astrocytes, allowing a greater increase in VDAC1-mediated cellular dysfunction in CA1 astrocytes. PMID- 27553864 TI - The epidemiology of metastases in neuroendocrine tumors. AB - The epidemiology of metastases in neuroendocrine tumors (NETs) is virtually unknown. The present novel approach took use of two nationwide Swedish registers to assess the distribution of metastatic sites in comparison to adenocarcinoma. 7,334 patients with NET were identified from the Swedish Cancer Registry. Metastatic sites were identified from the National Patient and Cause of Death Registries. Sites of metastasis were investigated depending on the primary site of NET. The metastatic potential of NET was assessed. The liver was the most common site of metastasis (82% of patients with metastases), and the small intestine was the most common source of NET metastases. Of all patients with metastatic lung NETs, 66% had liver metastases, whereas the corresponding number for adenocarcinoma of lung was only 20%. The risk of metastasis was highest if the primary was in the small intestine or pancreatohepatobiliary tract, whereas it was lower with appendiceal and rectal NET. Men had more bone metastases compared to women. Patients with metastatic NET had worse prognosis if the primary site was unknown (11 months, 9% of NET patients) compared to those whose primary was known (19 months). The metastatic potential of NETs varies profoundly depending on the primary site. NETs show a clear preference to metastasize to the liver. Surveillance of liver metastases may enable earlier diagnosis and treatment. In liver metastases from NET, the small intestine should be suspected as the primary site, whereas the lung should be suspected in nervous system metastases of NET origin. PMID- 27553865 TI - Victimization and Vulnerability: A Study of Incarceration, Interpersonal Trauma, and Patient-Physician Trust. AB - Despite the critical importance of patient-physician trust, it may be compromised among vulnerable patients, such as (1) incarcerated patients and (2) those patients who have been victims of trauma. The purpose of this study was to examine patient-physician trust among forensic and civilian psychiatric inpatient populations and to explore whether it varied based on a patient's history of incarceration and/or victimization. A trust survey (WFPTS) and a trauma instrument (LEC-5) were administered to 93 patients hospitalized on forensic and civilian psychiatric hospital units in a large, urban public hospital. Results showed no difference in patient-physician trust between incarcerated and civilian patients. Similarly, there was no effect of a history of physical assault or sexual assault on ratings of patient-physician trust. However, the hospitalized civilian and forensic patients who reported being the victim of weapons assault had significantly lower patient-physician trust scores than their counterparts. PMID- 27553866 TI - The International development of PROQOL-HCV: An instrument to assess the health related quality of life of patients treated for Hepatitis C virus. AB - BACKGROUND: Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). METHODS: HCV patients from France (n = 30), Brazil (n = 20) and Australia (n = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. RESULTS: Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) TREATMENT: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. CONCLUSION: We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension. PMID- 27553867 TI - EPHB4, a down stream target of IFN-gamma/STAT1 signal pathway, regulates endothelial activation possibly contributing to the development of preeclampsia. AB - PROBLEM: Preeclampsia is characterized by endothelial activation and excessive inflammation, of which interferon (IFN)-gamma is a potent inducer. Eph receptor B4 (EPHB4) also involved in endothelial activation in inflammation. Their role and relationship in preeclampsia remain unclear. METHOD OF STUDY: Intercellular adhesion molecular (ICAM)-1 was employed as the hallmark of endothelial activation. The serum levels of IFN-gamma and the expression of EPHB4 and ICAM-1 were assessed by ELISA, qRT-PCR and WB, respectively. Primary human umbilical vein endothelial cells (HUVECs) were treated with IFN-gamma of different concentration or for different times to determine the effect of IFN-gamma on EPHB4 and ICAM-1 expression. Overexpression and shRNA constructs, chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to clarify the regulation mechanism of IFN-gamma/STAT1 on EPHB4 resulting in HUVECs activation. Endothelial-trophoblast co-culture model was used to illustrate the role of EPHB4 in the process of activated endothelial cells resisting trophoblast invasion. RESULTS: IFN-gamma, EPHB4 and ICAM-1 expression were elevated in preeclampsia. IFN-gamma induced HUVECs activation through EPHB4 expression. ChIP and luciferase assays revealed that IFN-gamma promoted EPHB4 transcription by STAT-1 binding to EPHB4 promoter. EPHB4 probably involved in resisting trophoblasts displacement by IFN-gamma-activated HUVECs. CONCLUSION: This study uncovered the character of EPHB4-regulating endothelial activation in the pathogenesis of preeclampsia. PMID- 27553869 TI - Exploring the needs, concerns and knowledge of women diagnosed with gestational diabetes: A qualitative study. AB - OBJECTIVE: to explore the concerns, needs and knowledge of women diagnosed with Gestational Diabetes Mellitus (GDM). DESIGN: a qualitative study of women with GDM or a history of GDM. METHODS: nineteen women who were both pregnant and recently diagnosed with GDM or post- natal with a recent history of GDM were recruited from outpatient diabetes care clinics. This qualitative study utilised focus groups. Participants were asked a series of open-ended questions to explore (1) current knowledge of GDM; (2) anxiety when diagnosed with GDM, and whether this changed overtime; (3) understanding and managing GDM and (4) the future impact of GDM. The data were analysed using a conventional content analysis approach. FINDINGS: women experienced a steep learning curve when initially diagnosed and eventually became skilled at managing their disease effectively. The use of insulin was associated with fear and guilt. Diet advice was sometimes complex and not culturally appropriate. Women appeared not to be fully aware of the short or long-term consequences of a diagnosis of GDM. CONCLUSIONS: midwives and other Health Care Professionals need to be cognisant of the impact of a diagnosis of GDM and give individual and culturally appropriate advice (especially with regards to diet). High quality, evidence based information resources need to be made available to this group of women. Future health risks and lifestyle changes need to be discussed at diagnosis to ensure women have the opportunity to improve their health. PMID- 27553870 TI - Time and travel costs incurred by women attending antenatal tests: A costing study. AB - OBJECTIVE: to estimate the costs to women, their friends and family for different antenatal tests in the Down's syndrome (DS) screening pathway. DESIGN: questionnaire-based costing study. SETTING: eight maternity clinics across the UK. PARTICIPANTS: pregnant women (n=574) attending an appointment for DS screening, NIPT or invasive testing between December 2013 and September 2014. MEASUREMENTS: using data collected from the questionnaires we calculated the total costs to women by multiplying the time spent at the hospital and travelling to and from it by the opportunity costs of the women and accompanying person and adding travel and childcare costs. Assumptions about the value of opportunity costs were tested in one-way sensitivity analyses. The main outcome measure was the mean cost to the women and friends/family for each test (DS screening, NIPT, and invasive testing). FINDINGS: mean costs to women and their family/friend were L33.96 per visit, of which L22.47 were time costs, L9.15 were travel costs and L2.34 were childcare costs. Costs were lowest for NIPT (L22), L32 for DS screening (L44 if combined with NIPT), and highest for invasive testing (L60). Sensitivity analysis revealed that variations around the value of leisure time opportunity costs had the largest influence on the results. KEY CONCLUSIONS: there are considerable costs to women, their friends and family when attending different tests in the DS screening pathway. IMPLICATIONS FOR PRACTICE: when assessing the cost-effectiveness of changes to this pathway, costs to women should be considered. PMID- 27553871 TI - Renal outcomes after up to 8 years of tenofovir exposure in HIV-HBV-coinfected patients. AB - BACKGROUND: Renal toxicity is a common side effect during tenofovir (TDF)-use in HIV-infected, but not necessarily HBV-infected, patients. Nevertheless, little is known regarding TDF-use on renal impairment during HIV-HBV coinfection. We aimed to evaluate the progression and determinants of renal impairment in coinfected patients undergoing TDF. METHODS: A total of 175 coinfected patients initiating TDF-containing antiretroviral therapy were prospectively followed. Estimated glomerular filtration rates (eGFR) were calculated at baseline and every 6-12 months. Determinants of eGRF change from baseline (DeltaeGFR) were evaluated using mixed-effect linear regression and progression towards renal impairment using proportional-hazards regression. RESULTS: At baseline, average eGFR was 96.7 ml/min per 1.73m2 (95% CI 93.8, 99.6). During a median 58.3 months (IQR 33.7 92.1) of treatment, eGFR decreased a monthly average of -0.14 ml/min per 1.73m2 (95% CI -0.16, -0.12). Significantly faster DeltaeGFR was associated with baseline eGFR>90 (P=0.002), male gender (P=0.04), previous AIDS-defining illness at baseline (P=0.03), baseline liver cirrhosis (P=0.03) and concomitant protease inhibitor use (P=0.005). Between respective baseline and end of follow-up visits, the proportion of patients with renal impairment increased: normal function, 65.7% to 53.1%; mild impairment, 32.6% to 40.0%; moderate impairment, 1.7% to 6.9%. Higher age (P=0.01) and previous AIDS-defining illness (P=0.02) at baseline were independent risk-factors for developing impairment, while undetectable HBV DNA on-treatment was protective (P=0.006). Five (2.9%) patients permanently discontinued TDF after a renal event. CONCLUSIONS: Severe HIV-related and HBV related morbidity negatively affects renal function in coinfected patients undergoing long-term TDF. Although most patients only developed mild/moderate impairment, close renal monitoring is warranted for this particular population. PMID- 27553872 TI - Late gadolinium enhancement and adverse outcomes in a contemporary cohort of adult survivors of tetralogy of Fallot. AB - OBJECTIVE: Myocardial fibrosis has been associated with poorer outcomes in tetralogy of Fallot, however only a handful of studies have assessed its significance in the current era. Our aim was to quantify the amount of late gadolinium enhancement in both the LV and RV in a contemporary cohort of adults with surgically repaired tetralogy of Fallot, and assess the relationship with adverse clinical outcomes. DESIGN: Single centre cohort study SETTING: National tertiary referral center Patients: One hundred fourteen patients with surgically repaired tetralogy of Fallot with median age 29.5 years (range 17.5-64.2). Prospective follow-up for mean 2.4 years (SD 1.29). INTERVENTIONS: Cardiovascular magnetic resonance was performed, and late gadolinium enhancement mass was estimated for the LV using the 5-SD remote myocardium method, and for the RV using a segmental scoring system. Cohort characterization was determined through the use of a computerized database. OUTCOME MEASURES: Survival analysis from time of scan to first adverse event, defined as an episode of atrial arrhythmia, sustained ventricular arrhythmia, hospitalization with heart failure, or implantable cardioverter-defibrillator insertion. RESULTS: Eleven patients experienced an adverse outcome in the follow-up period, although there were no deaths. LV late gadolinium enhancement was associated with adverse outcomes in a univariate model (P = .027). However, when adjusted for age at scan the significant variables included NYHA class (P = .006), peak oxygen uptake (P = .028), number of prior sternotomies (P = .044), and higher indexed RV and LV end diastolic volumes (P = .002 and P < .001), but not RV or LV late gadolinium enhancement. CONCLUSIONS: Formal quantification of late gadolinium enhancement is not currently as helpful in ascertaining prognosis compared to other, more easily assessed parameters in a contemporary cohort of tetralogy of Fallot survivors, however assessment particularly of the LV holds promise for the future. PMID- 27553873 TI - Effect of interferon-beta1alpha therapy on multiple sclerosis based on gadolinium enhancing or active T2 magnetic resonance imaging outcomes: a meta-analysis. AB - OBJECTIVES: Interferon-beta1alpha (IFN-beta1alpha) is widely used to modify the course of relapsing-remitting multiple sclerosis. However, many patients have relapses. The purpose of this study was to evaluate magnetic resonance imaging (MRI) as a predictor of IFN-beta1alpha treatment efficacy in patients with MS. METHODS: PubMed, Embase, and the Cochrane Library were searched to identify eligible studies. Manual searches were also conducted. All eligible trials included MS patients who received IFN-beta1alpha based on gadolinium-enhancing or active T2 MRI lesions for determination of relapse rates. RESULTS: Of 499 identified studies, we included 10 trials reporting data on 6,037 MS patients. IFN-beta1alpha therapy significantly reduced the risk of relapse (RR: 0.87; 95% confidence intervals (CI): 0.76-0.99; p = 0.032). Furthermore, baseline median T2 lesion volume was found to be related to IFN-beta1alpha therapy and relapse (p = 0.018). Subgroup analysis suggested that IFN-beta1alpha therapy was associated with reduced risk of relapse (RR: 0.82; 95%CI: 0.71-0.94; p = 0.005 versus placebo). However, there was no significant difference in the risk of relapse compared to treatment with low dose IFN-beta1alpha (RR: 0.93; 95%CI: 0.80-1.08; p = 0.337) or glatiramer acetate (RR: 0.93; 95%CI: 0.77-1.14; p = 0.506). Finally, IFN-beta1alpha therapy significantly increased the risk of injection-site disorders, influenza-like syndrome, and alanine transferase elevation. DISCUSSION: Effects of IFN-beta1alpha therapy are associated with a statistically significant impact on baseline median T2 lesion volume. However, the safety outcomes are significantly worse in patients who receive IFN-beta1alpha therapy. PMID- 27553874 TI - Perenniality induces high inbreeding depression in self-fertilising species. AB - When predicting the fate and consequences of recurring deleterious mutations in self-fertilising populations most models developed make the assumption that populations have discrete non-overlapping generations. This makes them biologically irrelevant when considering perennial species with overlapping generations and where mating occurs independently of the age group. The few models studying the effect of perennial life-histories on the genetic properties of populations in the presence of self-fertilisation have done so considering age dependent selection. They find low levels of inbreeding depression in perennial populations that do not explain empirical observations. Here we propose a simple deterministic model in continuous time with selection at different fitness traits and feedback between population fitness and size. We find that a perennial life history can result in high levels of inbreeding depression in spite of inbreeding, due to higher frequencies of heterozygous individuals at the adult stage. We also propose that there may be demographic advantages for self fertilisation that are independent of reproductive success. PMID- 27553875 TI - Estimation of the HIV-1 backward mutation rate from transmitted drug-resistant strains. AB - One of the serious threats facing the administration of antiretroviral therapy to human immunodeficiency virus (HIV-1) infected patients is the reported increasing prevalence of transmitted drug resistance. However, given that HIV-1 drug resistant strains are often less fit than the wild-type strains, it is expected that drug-resistant strains that are present during the primary phase of the HIV 1 infection are replaced by the fitter wild-type strains. This replacement of HIV 1 resistant mutations involves the emergence of wild-type strains by a process of backward mutation. How quickly the replacement happens is dependent on the class of HIV-1 mutation group. We estimate the backward mutation rates and relative fitness of various mutational groups known to confer HIV-1 drug resistance. We do this by fitting a stochastic model to data for individuals who were originally infected by an HIV-1 strain carrying any one of the known drug resistance conferring mutations and observed over a period of time to see whether the resistant strain is replaced. To do this, we seek a distribution, generated from simulations of the stochastic model, that best describes the observed (clinical data) replacement times of a given mutation. We found that Lamivudine/Emtricitabine-associated mutations have a distinctly higher, backward mutation rate and low relative fitness compared to the other classes (as has been reported before) while protease inhibitors-associated mutations have a slower backward mutation rate and high relative fitness. For the other mutation classes, we found more uncertainty in their estimates. PMID- 27553876 TI - Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease. AB - Subthalamic nucleus (STN) local field potential (LFP) recordings demonstrate beta (13-30Hz) band oscillations in Parkinson's disease (PD) defined as elevations of spectral power. The amount of attenuation of beta band power on therapeutic levels of high frequency (HF) deep brain stimulation (DBS) and/or dopaminergic medication has been correlated with the degree of improvement in bradykinesia and rigidity from the therapy, which has led to the suggestion that elevated beta band power is a marker of PD motor disability. A fundamental question has not been answered: whether there is a prolonged attenuation of beta band power after withdrawal of chronic HF DBS and whether this is related to a lack of progression or even improvement in the underlying motor disability. Until now, in human PD subjects, STN LFP recordings were only attainable in the peri-operative period and after short periods of stimulation. For the first time, using an investigational, implanted sensing neurostimulator (Activa(r) PC+S, Medtronic, Inc.), STN LFPs and motor disability were recorded/assessed after withdrawal of chronic (6 and 12month) HF DBS in freely moving PD subjects. Beta band power was similar within 14s and 60min after stimulation was withdrawn, suggesting that "off therapy" experiments can be conducted almost immediately after stimulation is turned off. After withdrawal of 6 and 12months of STN DBS, beta band power was significantly lower (P<0.05 at 6 and 12months) and off therapy UPDRS scores were better (P<0.05 at 12months) compared to before DBS was started. The attenuation in beta band power was correlated with improvement in motor disability scores (P<0.05). These findings were supported by evidence of a gradual increase in beta band power in two unstimulated STNs after 24months and could not be explained by changes in lead impedance. This suggests that chronic HF DBS exerts long-term plasticity in the sensorimotor network, which may contribute to a lack of progression in underlying motor disability in PD. PMID- 27553878 TI - Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. AB - Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2-4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1/CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, or b) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease. PMID- 27553879 TI - Effect of storage time on gene expression data acquired from unfrozen archived newborn blood spots. AB - Unfrozen archived newborn blood spots (NBS) have been shown to retain sufficient messenger RNA (mRNA) for gene expression profiling. However, the effect of storage time at ambient temperature for NBS samples in relation to the quality of gene expression data is relatively unknown. Here, we evaluated mRNA expression from quantitative real-time PCR (qRT-PCR) and microarray data obtained from NBS samples stored at ambient temperature to determine the effect of storage time on the quality of gene expression. These data were generated in a previous case control study examining NBS in 53 children with cerebral palsy (CP) and 53 matched controls. NBS sample storage period ranged from 3 to 16years at ambient temperature. We found persistently low RNA integrity numbers (RIN=2.3+/-0.71) and 28S/18S rRNA ratios (~0) across NBS samples for all storage periods. In both qRT PCR and microarray data, the expression of three common housekeeping genes-beta cytoskeletal actin (ACTB), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and peptidylprolyl isomerase A (PPIA)-decreased with increased storage time. Median values of each microarray probe intensity at log2 scale also decreased over time. After eight years of storage, probe intensity values were largely reduced to background intensity levels. Of 21,500 genes tested, 89% significantly decreased in signal intensity, with 13,551, 10,730, and 9925 genes detected within 5years, > 5 to <10years, and >10years of storage, respectively. We also examined the expression of two gender-specific genes (X inactivation-specific transcript, XIST and lysine-specific demethylase 5D, KDM5D) and seven gene sets representing the inflammatory, hypoxic, coagulative, and thyroidal pathways hypothesized to be related to CP risk to determine the effect of storage time on the detection of these biologically relevant genes. We found the gender-specific genes and CP related gene sets detectable in all storage periods, but exhibited differential expression (between male vs. female or CP vs. control) only within the first six years of storage. We concluded that gene expression data quality deteriorates in unfrozen archived NBS over time and that differential gene expression profiling and analysis is recommended for those NBS samples collected and stored within six years at ambient temperature. PMID- 27553880 TI - A role for low-order system dynamics models in urban health policy making. AB - Cities are complex adaptive systems whose responses to policy initiatives emerge from feedback interactions between their parts. Urban policy makers must routinely deal with both detail and dynamic complexity, coupled with high levels of diversity, uncertainty and contingency. In such circumstances, it is difficult to generate reliable predictions of health-policy outcomes. In this paper we explore the potential for low-order system dynamics (LOSD) models to make a contribution towards meeting this challenge. By definition, LOSD models have few state variables (<=5), illustrate the non-linear effects caused by feedback and accumulation, and focus on endogenous dynamics generated within well-defined boundaries. We suggest that experience with LOSD models can help practitioners to develop an understanding of basic principles of system dynamics, giving them the ability to 'see with new eyes'. Because efforts to build a set of LOSD models can help a transdisciplinary group to develop a shared, coherent view of the problems that they seek to tackle, such models can also become the foundations of 'powerful ideas'. Powerful ideas are conceptual metaphors that provide the members of a policy-making group with the a priori shared context required for effective communication, the co-production of knowledge, and the collaborative development of effective public health policies. PMID- 27553877 TI - Post-traumatic administration of the p53 inactivator pifithrin-alpha oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury. AB - Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippocampus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-alpha oxygen analogue (PFT-alpha (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-alpha (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region's role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-alpha or PFT-alpha (O) (2mg/kg, i.v.) or vehicle at 5h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24h and 7days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-alpha and, particularly, PFT-alpha (O) at 5h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7days after TBI, as evaluated by novel object recognition and open-field test. PFT-alpha and especially PFT-alpha (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-alpha (O), but not PFT-alpha, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-alpha (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-alpha (O) after TBI. Our data suggest that PFT-alpha and especially PFT alpha (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties. PMID- 27553881 TI - Entanglement transfer from two-mode continuous variable SU(2) cat states to discrete qubits systems in Jaynes-Cummings Dimers. AB - We study the entanglement transfer from a two-mode continuous variable system (initially in the two-mode SU(2) cat states) to a couple of discrete two-state systems (initially in an arbitrary mixed state), by use of the resonant Jaynes Cummings (JC) interaction. We first quantitatively connect the entanglement transfer to non-Gaussianity of the two-mode SU(2) cat states and find a positive correlation between them. We then investigate the behaviors of the entanglement transfer and find that it is dependent on the initial state of the discrete systems. We also find that the largest possible value of the transferred entanglement exhibits a variety of behaviors for different photon number as well as for the phase angle of the two-mode SU(2) cat states. We finally consider the influences of the noise on the transferred entanglement. PMID- 27553882 TI - Higher fungal diversity is correlated with lower CO2 emissions from dead wood in a natural forest. AB - Wood decomposition releases almost as much CO2 to the atmosphere as does fossil fuel combustion, so the factors regulating wood decomposition can affect global carbon cycling. We used metabarcoding to estimate the fungal species diversities of naturally colonized decomposing wood in subtropical China and, for the first time, compared them to concurrent measures of CO2 emissions. Wood hosting more diverse fungal communities emitted less CO2, with Shannon diversity explaining 26 to 44% of emissions variation. Community analysis supports a 'pure diversity' effect of fungi on decomposition rates and thus suggests that interference competition is an underlying mechanism. Our findings extend the results of published experiments using low-diversity, laboratory-inoculated wood to a high diversity, natural system. We hypothesize that high levels of saprotrophic fungal biodiversity could be providing globally important ecosystem services by maintaining dead-wood habitats and by slowing the atmospheric contribution of CO2 from the world's stock of decomposing wood. However, large-scale surveys and controlled experimental tests in natural settings will be needed to test this hypothesis. PMID- 27553883 TI - Metabolic engineering of Corynebacterium glutamicum for shikimate overproduction by growth-arrested cell reaction. AB - Corynebacterium glutamicum with the ability to simultaneously utilize glucose/pentose mixed sugars was metabolically engineered to overproduce shikimate, a valuable hydroaromatic compound used as a starting material for the synthesis of the anti-influenza drug oseltamivir. To achieve this, the shikimate kinase and other potential metabolic activities for the consumption of shikimate and its precursor dehydroshikimate were inactivated. Carbon flux toward shikimate synthesis was enhanced by overexpression of genes for the shikimate pathway and the non-oxidative pentose phosphate pathway. Subsequently, to improve the availability of the key aromatics precursor phosphoenolpyruvate (PEP) toward shikimate synthesis, the PEP: sugar phosphotransferase system (PTS) was inactivated and an endogenous myo-inositol transporter IolT1 and glucokinases were overexpressed. Unexpectedly, the resultant non-PTS strain accumulated 1,3 dihydroxyacetone (DHA) and glycerol as major byproducts. This observation and metabolome analysis identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzed reaction as a limiting step in glycolysis. Consistently, overexpression of GAPDH significantly stimulated both glucose consumption and shikimate production. Blockage of the DHA synthesis further improved shikimate yield. We applied an aerobic, growth-arrested and high-density cell reaction to the shikimate production by the resulting strain and notably achieved the highest shikimate titer (141g/l) and a yield (51% (mol/mol)) from glucose reported to date after 48h in minimal medium lacking nutrients required for cell growth. Moreover, comparable shikimate productivity could be attained through simultaneous utilization of glucose, xylose, and arabinose, enabling efficient shikimate production from lignocellulosic feedstocks. These findings demonstrate that C. glutamicum has significant potential for the production of shikimate and derived aromatic compounds. PMID- 27553884 TI - Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum. AB - The performance of Corynebacterium glutamicum cell factories producing compounds which rely heavily on NADPH has been reported to depend on the sugar being metabolized. While some aspects of this phenomenon have been elucidated, there are still many unresolved questions as to how sugar metabolism is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed us to propose a simple model explaining the correlation between sugar phosphate concentration, gene expression and ultimately the observed phenotype. To guide us in our analysis and help us identify bottlenecks in metabolism we debugged an existing genome-scale model onto which we overlaid the transcriptome data. Based on the results obtained we managed to enhance the NADPH supply and transform the wild-type strain into delivering the highest yield of lysine ever obtained on sucrose and fructose, thus providing a good example of how regulatory mechanisms can be harnessed for bioproduction. PMID- 27553885 TI - Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells. AB - Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations. PMID- 27553887 TI - Agricultural anaerobic digestion power plants in Ireland and Germany: policy and practice. AB - The process of anaerobic digestion (AD) is valued as a carbon-neutral energy source, while simultaneously treating organic waste, making it safer for disposal or use as a fertilizer on agricultural land. The AD process in many European nations, such as Germany, has grown from use of small, localized digesters to the operation of large-scale treatment facilities, which contribute significantly to national renewable energy quotas. However, these large AD plants are costly to run and demand intensive farming of energy crops for feedstock. Current policy in Germany has transitioned to support funding for smaller digesters, while also limiting the use of energy crops. AD within Ireland, as a new technology, is affected by ambiguous governmental policies concerning waste and energy. A clear governmental strategy supporting on-site AD processing of agricultural waste will significantly reduce Ireland's carbon footprint, improve the safety and bioavailability of agricultural waste, and provide an indigenous renewable energy source. (c) 2016 Society of Chemical Industry. PMID- 27553886 TI - Neuroprotective Effect of Electric Conduction Treatment on Hippocampus Cell Apoptosis in KA Induced Acute Temporal Lobe Epileptic Rats. AB - BACKGROUND: Electronic conduction, a new treatment approach for epilepsy, has been confirmed to reduce epileptiform discharge on EEG and convulsive behaviors, particularly epileptic discharge propagation and serious behavioral seizures, in rats with kainic acid (KA)-induced acute temporal lobe epilepsy (TLE). OBJECTIVE: Hippocampal cell apoptosis was examined to confirm the neuroprotective effect of electronic conduction therapy in rats with KA-induced acute TLE. METHODS: Rats were divided into four groups: control group (right CA3 injection of saline), KA group (right CA3 injection of KA), sham conduction group (KA rats with sham conduction), and conduction group (KA rats with electric conduction). Apoptotic cells were evaluated by flow cytometry, TUNEL staining, and mRNA expression levels of caspase-3, tumor necrosis factor-alpha, and glial fibrillary acidic protein measured by real-time quantitative PCR (qRT-PCR). RESULTS: The frequency of convulsive behaviors in the conduction group decreased significantly compared with the KA group and the sham conduction group. Significantly fewer apoptotic cells were detected in rats with conduction based on flow cytometry and TUNEL staining results. The qRT-PCR results indicated that KA-induced up-regulation of hippocampal caspase-3 mRNA expression was reduced 24 hours after KA injection in rats that received conduction treatment. CONCLUSION: Electronic conduction treatment can reduce seizure frequency and hippocampal cell apoptosis in rats with KA-induced acute TLE. PMID- 27553888 TI - Chiral light intrinsically couples to extrinsic/pseudo-chiral metasurfaces made of tilted gold nanowires. AB - Extrinsic or pseudo-chiral (meta)surfaces have an achiral structure, yet they can give rise to circular dichroism when the experiment itself becomes chiral. Although these surfaces are known to yield differences in reflected and transmitted circularly polarized light, the exact mechanism of the interaction has never been directly demonstrated. Here we present a comprehensive linear and nonlinear optical investigation of a metasurface composed of tilted gold nanowires. In the linear regime, we directly demonstrate the selective absorption of circularly polarised light depending on the orientation of the metasurface. In the nonlinear regime, we demonstrate for the first time how second harmonic generation circular dichroism in such extrinsic/pseudo-chiral materials can be understood in terms of effective nonlinear susceptibility tensor elements that switch sign depending on the orientation of the metasurface. By providing fundamental understanding of the chiroptical interactions in achiral metasurfaces, our work opens up new perspectives for the optimisation of their properties. PMID- 27553889 TI - Impact on patient outcome of emergency department length of stay prior to ICU admission. AB - OBJECTIVE: The favorable evolution of critically ill patients is often dependent on time-sensitive care intervention. The timing of transfer to the intensive care unit (ICU) therefore may be an important determinant of outcomes in critically ill patients. The aim of this study was to analyze the impact upon patient outcome of the length of stay in the Emergency Care Department. DESIGN: A single center ambispective cohort study was carried out. SETTING: A general ICU and Emergency Care Department (ED) of a single University Hospital. PATIENTS: We included 269 patients consecutively transferred to the ICU from the ED over an 18 month period. INTERVENTIONS: Patients were first grouped into different cohorts based on ED length of stay (LOS), and were then divided into two groups: (a) ED LOS <=5h and (b) ED LOS >5h. VARIABLES: Demographic, diagnostic, length of stay and mortality data were compared among the groups. RESULTS: Median ED LOS was 277min (IQR 129-622). Patients who developed ICU complications had a longer ED LOS compared to those who did not (349min vs. 209min, p<0.01). A total of 129 patients (48%) had ED LOS >5h. The odds ratio of dying for patients with ED LOS >5h was 2.5 (95% CI 1.3-4.7). Age and sepsis diagnosis were the risk factors associated to prolongation of ED length of stay. CONCLUSIONS: A prolonged ED stay prior to ICU admission is related to the development of time-dependent complications and increased mortality. These findings suggest possible benefit from earlier ICU transfer and the prompt initiation of organ support. PMID- 27553891 TI - Diagnosis and treatment of pulmonary alveolar microlithiasis. AB - Pulmonary alveolar microlithiasis (PAM) is a rare genetic disease caused by mutations in sodium-phosphate co-transporter (SLC34A2), which encodes a type 2b sodium phosphate co-transporter. Disease is characterized by intra-alveolar microlith formation of phosphate. Turkey has a high prevalence of PAM. Herein, we report the clinical and radiological findings of three patients diagnosed with PAM and treated with disodium etidronate. PMID- 27553890 TI - Left ventricular non-compaction revealed by aortic regurgitation due to Kawasaki disease in a boy with LDB3 mutation. AB - Kawasaki disease (KD) is an acute febrile illness of childhood characterized by systemic vasculitis, especially coronary arteritis. Aortic valve regurgitation (AVR) is a relatively common complication. There have been no reports to date of heart failure and left ventricular non-compaction (LVNC) after acute KD, although the precise etiology of this condition remains unclear. A 6-month-old boy with KD was admitted to hospital. Despite high-dose i.v. gammaglobulin for dilation of the coronary artery, moderate AVR appeared, and thereafter he developed heart failure. A rough, dense LV myocardium indicated LVNC. On genetic testing a heterogenous 163G > A substitution changing a valine to isoleucine in LIM domain binding protein 3 (LDB3) was identified. Additional cardiac stress, such as that caused by AVR and/or KD might have triggered cardiac failure in the form of LVNC due to LDB3 mutation. PMID- 27553892 TI - Is there a role for stool metabolomics in cystic fibrosis? AB - A number of studies utilizing metabolomics have focused on the pathophysiology of cystic fibrosis (CF) lung disease. Here, we performed fecal metabolomics on pancreatic insufficient (PI) and sufficient (PS) children with CF and compared them with healthy controls (HC). Fecal metabolomics can differentiate between PS CF and PI-CF. We identified a potential biomarker of disease severity or cystic fibrosis transmembrane conductance regulator function (m/z, 463.247; retention time, 0.570717 min) that discriminates between HC versus PS-CF versus PI-CF. We also identified lipoyl-GMP as a potential novel inflammatory biomarker, and elevation in fecal glycerol 1,2-didodecanoate 3-tetradecanoate may provide clues to the pathogenesis of intestinal inflammation. For the first time, we demonstrate the potential applications of fecal metabolomics in CF. PMID- 27553893 TI - Right Ventricular Versus Biventricular Pacing for Heart Failure and Atrioventricular Block. AB - The use of cardiac resynchronization therapy (CRT) is well accepted as an important option for the treatment of patients with systolic heart failure and prolonged QRS duration. CRT for patients with narrow QRS complexes is reserved for patients who are undergoing implantation of new or replacement pacemakers or implantable cardioverter defibrillators with an anticipated significant requirement for ventricular pacing. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial examined the role of CRT in heart failure patients with atrioventricular block and demonstrated significantly better outcomes with CRT compared to right ventricular pacing. On the other hand, conflicting preliminary data were reported by the Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) Trial investigators. In this review, we will discuss the adverse consequences of chronic right ventricular pacing, the options of alternate pacing sites in the right ventricle versus biventricular pacing, and the findings from the BLOCK HF Trial as well as the preliminary data from the BioPace Trial. Our goal is to explore the role of biventricular pacing in patients with atrioventricular block. PMID- 27553894 TI - Ultra-wide field imaging of retinal haemangioma in retinitis pigmentosa. PMID- 27553895 TI - Re: Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of the jaws?-a response. PMID- 27553896 TI - Painful temporomandibular disorders and central sensitization: implications for management-a pilot study. AB - The objective was to investigate the presence of cutaneous allodynia and hyperalgesia in the trigeminal and extra-trigeminal areas, as a surrogate for central sensitization (CS), in women with a painful temporomandibular disorder (TMD) and without other painful conditions. Painful TMDs, depression, and non specific physical symptoms (NSPS) were classified according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The amount of pain in the trigeminal and extra-trigeminal areas was determined using a visual analogue scale (0-100mm) after the application of a vibrotactile stimulus and assessment of the pressure pain threshold (PPT). Statistical tests (Fisher's, chi2, and Mann-Whitney) were performed, with a significance level of 5%. The sample comprised 45 women (mean age 37.5 years; 16 with a painful TMD) who were free of any headache, fibromyalgia, or other painful condition. Painful TMD was associated with higher pain sensitivity and lower PPT values in the trigeminal (P<0.01) and extra-trigeminal regions (P<0.01). The presence of depression contributed significantly to increased pain sensitivity. The presence of hyperalgesia and allodynia in both the trigeminal and extra-trigeminal regions among women with a painful TMD indicated the presence of CS. Changes involving the central nervous system should be considered during the evaluation and management of patients with a painful TMD. PMID- 27553897 TI - Reciprocal Self-Assembly of Peptide-DNA Conjugates into a Programmable Sub-10-nm Supramolecular Deoxyribonucleoprotein. AB - To overcome the limitations of molecular assemblies, the development of novel supramolecular building blocks and self-assembly modes is essential to create more sophisticated, complex, and controllable aggregates. The self-assembly of peptide-DNA conjugates (PDCs), in which two orthogonal self-assembly modes, that is, beta-sheet formation and Watson-Crick base pairing, are covalently combined in one supramolecular system, is reported. Despite extensive research, most self assembly studies have focused on using only one type of building block, which restricts structural and functional diversity compared to multicomponent systems. Multicomponent systems, however, suffer from poor control of self-assembly behaviors. Covalently conjugated PDC building blocks are shown to assemble into well-defined and controllable nanostructures. This controllability likely results from the decrease in entropy associated with the restriction of the molecular degrees of freedom by the covalent constraints. Using this strategy, the possibility to thermodynamically program nano-assemblies to exert gene regulation activity with low cytotoxicity is demonstrated. PMID- 27553898 TI - Electron Transport Layer-Free Solar Cells Based on Perovskite-Fullerene Blend Films with Enhanced Performance and Stability. AB - The solution processing of pinhole-free methylammonium lead triiodide perovskite C70 fullerene (MAPbI3 :C70 ) blend films on fluorine-doped tin oxide (FTO)-coated glass substrates is presented. Based on this approach, a simplified and robust protocol for the preparation of efficient electron-transport layer (ETL)-free perovskite solar cells is described. Power conversion efficiency (PCE) of 13.6 % under AM 1.5 G simulated sunlight is demonstrated for these devices. Comparative impedance spectroscopy and photostability analysis of the MAPbI3 :C70 and single MAPbI3 films compared with conventional compact TiO2 ETL-based devices are shown. The beneficial impact of using MAPbI3 :C70 blend films is emphasized. PMID- 27553901 TI - Sub-2 nm Thick Fluoroalkylsilane Self-Assembled Monolayer-Coated High Voltage Spinel Crystals as Promising Cathode Materials for Lithium Ion Batteries. AB - We demonstrate herein that an ultra-thin fluoroalkylsilane self-assembled monolayer coating can be used as a modifying agent at LiNi0.5Mn1.5O4 deltacathode/electrolyte interfaces in 5V-class lithium-ion batteries. Bare LiNi0.5Mn1.5O4-delta cathode showed substantial capacity fading, with capacity dropping to 79% of the original capacity after 100 cycles at a rate of 1C, which was entirely due to dissolution of Mn(3+) from the spinel lattice via oxidative decomposition of the organic electrolyte. Capacity retention was improved to 97% on coating ultra-thin FAS17-SAM onto the LiNi0.5Mn1.5O4 cathode surface. Such surface protection with highly ordered fluoroalkyl chains insulated the cathode from direct contact with the organic electrolyte and led to increased tolerance to HF. PMID- 27553900 TI - Endothelin-1 mediated induction of extracellular matrix genes in strial marginal cells underlies strial pathology in Alport mice. AB - Alport syndrome, a type IV collagen disorder, manifests as glomerular disease associated with hearing loss with thickening of the glomerular and strial capillary basement membranes (SCBMs). We have identified a role for endothelin-1 (ET-1) activation of endothelin A receptors (ETARs) in glomerular pathogenesis. Here we explore whether ET-1 plays a role in strial pathology. Wild type (WT) and Alport mice were treated with the ETAR antagonist, sitaxentan. The stria vascularis was analyzed for SCBM thickness and for extracellular matrix (ECM) proteins. Additional WT and Alport mice were exposed to noise or hypoxia and the stria analyzed for hypoxia-related and ECM genes. A strial marginal cell line cultured under hypoxic conditions, or stimulated with ET-1 was analyzed for expression of hypoxia-related and ECM transcripts. Noise exposure resulted in significantly elevated ABR thresholds in Alport mice relative to wild type littermates. Alport stria showed elevated expression of collagen alpha1(IV), laminin alpha2, and laminin alpha5 proteins relative to WT. SCBM thickening and elevated ECM protein expression was ameliorated by ETAR blockade. Stria from normoxic Alport mice and hypoxic WT mice showed upregulation of hypoxia-related, ECM, and ET-1 transcripts. Both ET-1 stimulation and hypoxia up-regulated ECM transcripts in cultured marginal cells. We conclude that ET-1 mediated activation of ETARs on strial marginal cells results in elevated expression of ECM genes and thickening of the SCBMs in Alport mice. SCBM thickening results in hypoxic stress further elevating ECM and ET-1 gene expression, exacerbating strial pathology. PMID- 27553902 TI - A study of the peopling of Greenland using next generation sequencing of complete mitochondrial genomes. AB - OBJECTIVES: The Greenlandic population history is characterized by a number of migrations of people of various ethnicities. In this work, the analysis of the complete mtDNA genome aimed to contribute to the ongoing debate on the origin of current Greenlanders and, at the same time, to address the migration patterns in the Greenlandic population from a female inheritance demographic perspective. METHODS: We investigated the maternal genetic variation in the Greenlandic population by sequencing the whole mtDNA genome in 127 Greenlandic individuals using the Illumina MiSeq(r) platform. RESULTS: All Greenlandic individuals belonged to the Inuit mtDNA lineages A2a, A2b1, and D4b1a2a1. No European haplogroup was found. DISCUSSION: The mtDNA lineages seem to support the hypothesis that the Inuit in Greenland are descendants from the Thule migration. The results also reinforce the importance of isolation and genetic drift in shaping the genetic diversity in Greenlanders. Based on the mtDNA sequences, the Greenlandic Inuit are phylogenetically close to Siberian groups and Canadian Inuit. PMID- 27553899 TI - Auditory thalamic circuits and GABAA receptor function: Putative mechanisms in tinnitus pathology. AB - Tinnitus is defined as a phantom sound (ringing in the ears), and can significantly reduce the quality of life for those who suffer its effects. Ten to fifteen percent of the general adult population report symptoms of tinnitus with 1-2% reporting that tinnitus negatively impacts their quality of life. Noise exposure is the most common cause of tinnitus and the military environment presents many challenging high-noise situations. Military noise levels can be so intense that standard hearing protection is not adequate. Recent studies suggest a role for inhibitory neurotransmitter dysfunction in response to noise-induced peripheral deafferentation as a key element in the pathology of tinnitus. The auditory thalamus, or medial geniculate body (MGB), is an obligate auditory brain center in a unique position to gate the percept of sound as it projects to auditory cortex and to limbic structures. Both areas are thought to be involved in those individuals most impacted by tinnitus. For MGB, opposing hypotheses have posited either a tinnitus-related pathologic decrease or pathologic increase in GABAergic inhibition. In sensory thalamus, GABA mediates fast synaptic inhibition via synaptic GABAA receptors (GABAARs) as well as a persistent tonic inhibition via high-affinity extrasynaptic GABAARs and slow synaptic inhibition via GABABRs. Down-regulation of inhibitory neurotransmission, related to partial peripheral deafferentation, is consistently presented as partially underpinning neuronal hyperactivity seen in animal models of tinnitus. This maladaptive plasticity/Gain Control Theory of tinnitus pathology (see Auerbach et al., 2014; Richardson et al., 2012) is characterized by reduced inhibition associated with increased spontaneous and abnormal neuronal activity, including bursting and increased synchrony throughout much of the central auditory pathway. A competing hypothesis suggests that maladaptive oscillations between the MGB and auditory cortex, thalamocortical dysrhythmia, predict tinnitus pathology (De Ridder et al., 2015). These unusual oscillations/rhythms reflect net increased tonic inhibition in a subset of thalamocortical projection neurons resulting in abnormal bursting. Hyperpolarizing de-inactivation of T-type Ca2+ channels switches thalamocortical projection neurons into burst mode. Thalamocortical dysrhythmia originating in sensory thalamus has been postulated to underpin neuropathies including tinnitus and chronic pain. Here we review the relationship between noise-induced tinnitus and altered inhibition in the MGB. PMID- 27553904 TI - Empiricism and language learnability. PMID- 27553903 TI - Unraveling the Hydrolysis of Merocyanine-Based Probes in Biological Assay. AB - Merocyanine dyes, owing to their unique photochemical properties, are widely used to fabricate probes for the detection of biologically active small molecules and bioimaging. In this paper, merocyanine-based probes were proved of undergoing unwanted hydrolysis. To explore the strategies toward avoiding the hydrolysis, the detailed hydrolysis mechanism was first investigated, which was also confirmed by density functional theory (DFT) calculation. Then a series of merocyanine dyes were rationally designed. Influences of molecular structures of the probes, the analytical media such as pH and components of the solution on the hydrolysis were systematically studied. The experimental results suggest that merocyanine based probes with low electron density are more likely to suffer the hydrolysis, which could be exacerbated by the well-accepted strategy for constructing type-II probes. It is worth noting that chemical surroundings could also exert distinctive influence on the hydrolysis. The hydrolysis could be obviously aggravated when fetal calf serum or DMSO was deployed. Our findings will definitely provide an effective and reliable approach for guiding the rational design of highly robust merocyanine-based probes and the optimization of the analytical media, which is helpful in terms of avoiding the hydrolysis of the probes and hydrolysis caused analytical errors. PMID- 27553906 TI - The Potential Value of Immunotherapy in Colorectal Cancers: Review of the Evidence for Programmed Death-1 Inhibitor Therapy. AB - Colorectal cancers (CRCs) have been identified as potential targets for immunotherapy with programmed cell death (PD)-1 inhibitors. English-language publications from MedLine and Embase that evaluated PD-1/PD ligand 1 (PD-L1) in the CRC tumor microenvironment and clinical trials that assessed PD-1 inhibitors were included. Sixteen abstracts were screened. Fifteen met the inclusion criteria. After review of the full texts, this resulted in a final reference list of 8 studies eligible for review. Five studies that assessed PD-1/PD-L1 in CRC and 3 trials that assessed PD-1 inhibitors were included. PD-1-positive (PD-1+) tumor-infiltrating lymphocytes and PD-L1+ cancer cells featured more prominently in high-level microsatellite instability (MSI-H) CRCs compared with microsatellite stable (MSS) CRCs, except in 1 study in which PD-L1 expression was higher in MSS CRCs. In the 3 trials that assessed PD-1 inhibitor, all 3 studies recruited patients with metastatic CRC (mCRC). One study also included patients with recurrent CRC. The objective response according to the Response Evaluation Criteria in Solid Tumors criteria was 0% (19 CRC patients with unknown microsatellite instability status) in the nivolumab study. In the pembrolizumab study, the objective response to PD-1 inhibitor was 40% and 0% in patients with MSI-H and MSS mCRC, respectively (10 patients in the MSI-H group, 18 patients in the MSS group). Seventy-eight percent of the patients in the MSI-H mCRC group compared with 11% in the MSS mCRC group (P < .005) showed no further disease progression at 12 weeks. In the nivolumab with or without ipilimumab study, objective partial response at 12 weeks to PD-1 inhibitor with or without cytotoxic T-lymphocyte-associated protein 4 inhibitor was 25.5% to 33.3% and 5% in the MSI-H and MSS groups, respectively (100 patients in the MSI-H group, 20 patients in the MSS group). Clinical trials that assessed PD-1 inhibitor immunotherapy in patients with CRC have recruited only small cohorts of patients with mCRC. Studies on the tumor microenvironment have been on the basis of archival specimens with different antibody PD-1 and PD-L1 preparations for immunohistochemistry, independent from immunotherapy trials. Immunotherapy with PD-1 therapy has potential benefit for immunogenic MSI-H CRCs whereas there is no evidence to date to suggest immunotherapy benefit in MSS CRCs. The available data are limited, and there is no information on non-mCRCs. Future trials are under way to determine its benefits. PMID- 27553905 TI - Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2, and autophagy pathways. AB - Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has been shown to be neuroprotective in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of sulforaphane in an in vivo Parkinson's disease (PD) model, based on rotenone-mediated neurotoxicity. Our results showed that sulforaphane inhibited rotenone-induced locomotor activity deficiency and dopaminergic neuronal loss. Additionally, sulforaphane treatment inhibited the rotenone-induced reactive oxygen species production, malondialdehyde (MDA) accumulation, and resulted in an increased level of total glutathione and reduced glutathione (GSH): oxidized glutathione (GSSG) in the brain. Western blot analysis illustrated that sulforaphane increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1), the latter two of which are anti-oxidative enzymes. Moreover, sulforaphane treatment significantly attenuated rotenone-inhibited mTOR mediated p70S6K and 4E-BP1 signalling pathway, as well as neuronal apoptosis. In addition, sulforaphane rescued rotenone-inhibited autophagy, as detected by LC3 II. Collectively, these findings demonstrated that sulforaphane exert neuroprotective effect involving Nrf2-dependent reductions in oxidative stress, mTOR-dependent inhibition of neuronal apoptosis, and the restoration of normal autophagy. Sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing PD. PMID- 27553907 TI - Metastatic Colorectal Cancer in Hispanics: Treatment Outcomes in a Treated Population. AB - BACKGROUND: In United States Hispanics have disparities in the presentation and outcome of colorectal cancer (CRC) largely attributed to their late presentation and lower socioeconomic status. Impact of treatment, especially in the metastatic setting, in the observed outcome is an unexplored area. We explored the role of treatment in the outcome of metastatic CRC we performed a retrospective analysis to assess the contribution of demographics, tumor characteristics, and health care setting on survival differences. PATIENTS AND METHODS: We conducted a retrospective study of patients who were treated with metastatic CRC at Los Angeles County Hospital-University of Southern California (LAC-USC, a public hospital) and Norris Comprehensive Cancer Center (NCCC, private hospital) between 2002 and 2012. Both these institutions are staffed by the same providers and therefore treatment algorithms and access to drugs were similar. We identified metastatic CRC patients who received chemotherapy from administrative records. Demographics, tumor, and treatment related factors were collected. The primary end point was time to progression (TTP: time from the first day of chemotherapy to the date of progression). Overall survival (OS) was measured from the first day of chemotherapy to death or last follow-up. Descriptive statistics were used to describe the population and chi-square, Wilcoxon, and log-rank tests were used for comparison between the groups. RESULTS: A total of 242 patients, 44% Hispanic, 26% non-Hispanic whites (NHWs), 21% Asian and 9% black were included. Median TTP was 9.2 months (95% confidence interval [CI], 7.6-11.6) in Hispanics, and 20.7 months (95% CI, 9.6-27.5; P < .05) in NHWs. Median OS in Hispanics was 16.3 months (95% CI, 13.3-18.5), and in NHWs was 33.5 months (95% CI, 22.1-63.6; P < .001). Hispanics who were treated at LAC-USC had longer TTP in comparison to Hispanics at NCCC (P = .04). CONCLUSION: Hispanics with metastatic CRC have shorter TTP and OS on first line therapy when adjusted for health care setting, demographics, disease characteristics, and treatment factors. PMID- 27553908 TI - Key factors of eddy current separation for recovering aluminum from crushed e waste. AB - Recovery of e-waste in China had caused serious pollutions. Eddy current separation is an environment-friendly technology of separating nonferrous metallic particles from crushed e-waste. However, due to complex particle characters, separation efficiency of traditional eddy current separator was low. In production, controllable operation factors of eddy current separation are feeding speed, (omegaR-v), and Sp. There is little special information about influencing mechanism and critical parameters of these factors in eddy current separation. This paper provided the special information of these key factors in eddy current separation of recovering aluminum particles from crushed waste refrigerator cabinets. Detachment angles increased as the increase of (omegaR-v). Separation efficiency increased with the growing of detachment angles. Aluminum particles were completely separated from plastic particles in critical parameters of feeding speed 0.5m/s and detachment angles greater than 6.61deg. Sp/Sm of aluminum particles in crushed waste refrigerators ranged from 0.08 to 0.51. Separation efficiency increased as the increase of Sp/Sm. This enlightened us to develop new separator to separate smaller nonferrous metallic particles in e waste recovery. High feeding speed destroyed separation efficiency. However, greater Sp of aluminum particles brought positive impact on separation efficiency. Greater Sp could increase critical feeding speed to offer greater throughput of eddy current separation. This paper will guide eddy current separation in production of recovering nonferrous metals from crushed e-waste. PMID- 27553909 TI - Leachate flow around a well in MSW landfill: Analysis of field tests using Richards model. AB - During the lifespan of a Municipal Solid Waste landfill, its leachate drainage system may get clogged. Then, as a consequence of rainfall, leachate generation and possibly leachate injection, the moisture content in the landfill increases to the point that a leachate mound could be created. Therefore, pumping the leachate becomes a necessary solution. This paper presents an original analysis of leachate pumping and injection in an instrumented well. The water table level around the well is monitored by nine piezometers which allow the leachate flow behaviour to be captured. A numerical model based on Richards equation and an exponential relationship between saturated hydraulic conductivity and depth is used to analyze the landfill response to pumping and injection. Decreasing permeability with depth appears to have a major influence on the behaviour of the leachate flow. It could have a drastic negative impact on the pumping efficiency with a maximum quasi-stationary pumping rate limited to approximately 1m3/h for the tested well and the radius of influence is less than 20m. The numerical model provides a reasonable description of both pumping and injection tests. However, an anomalous behaviour observed at the transition between pumping and recovery phases is observed. This could be due to a limitation of the Richards model in that it neglects the gas phase behaviour and other double porosity heterogeneous effects. PMID- 27553910 TI - Green Synthesis of Red-Emitting Carbon Nanodots as a Novel "Turn-on" Nanothermometer in Living Cells. AB - Temperature measurements in biology and medical diagnostics, along with sensitive temperature probing of living cells, is of great importance; however, it still faces significant challenges. Herein, a novel "turn-on" carbon-dot-based fluorescent nanothermometry device for spatially resolved temperature measurements in living cells is presented. The carbon nanodots (CNDs) are prepared by a green microwave-assisted method and exhibit red fluorescence (lambdaem =615 nm) with high quantum yields (15 %). Then, an on-off fluorescent probe is prepared for detecting glutathione (GSH) based on aggregation-induced fluorescence quenching. Interestingly, the quenched fluorescence could be recovered by increasing temperature and the CNDs-GSH mixture could behave as an off-on fluorescent probe for temperature. Thus, red-emitting CNDs can be utilized for "turn-on" fluorescent nanothermometry through the fluorescence quenching and recovery processes, respectively. We employ MC3T3-E1 cells as an example model to demonstrate the red-emitting CNDs can function as "non-contact" tools for the accurate measurement of temperature and its gradient inside a living cell. PMID- 27553911 TI - Observations on conducting whole-cell patch clamping of the hERG cardiac K+ channel in pure human serum. AB - Inhibition of the human ether-a-go-go-related gene (hERG) K+ channel by drugs leads to QT prolongation on the electrocardiogram and can result in serious cardiac arrhythmia. For this reason, screening of drugs on hERG is mandatory during the drug development process. Patch clamp electrophysiology in a defined physiological saline solution (PSS) represents the standard method for assaying drug effects on the channel. To make the assay more translatable to clinical studies, we have conducted whole-cell patch clamping of hERG using pure human serum as the extracellular medium. Pure human serum had little effect on the hERG channel waveform or the current-voltage relationship when compared to PSS. hERG current recordings were highly stable in serum at room temperature, but prolonged recordings at the physiological temperature required prior heat inactivation of the serum. Compared to PSS, the IC50 values, conducted at room temperature, of the classic hERG blocking drugs cisapride, moxifloxacin, and terfenadine were shifted to the right by an extent predicted by their known plasma protein binding, but we did not detect any differences in IC50 s between male and female serum. Total plasma levels of these drugs associated with clinical QT prolongation corresponded to small (<15%) inhibition of hERG current in pure serum suggesting that minor inhibition of the channel leads to observable pharmacodynamic effects. Conducting whole-cell patch clamping of hERG in human serum has the potential to make the assay more translatable to clinical studies and improve its predictive value for safety testing. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27553912 TI - Faster rate of blood volume change in pediatric hemodialysis patients impairs cardiac index. AB - BACKGROUND: Intradialytic hypotension and myocardial stunning are proposed as contributing to the pathogenesis of increased cardiovascular disease burden and death in patients receiving maintenance hemodialysis (HD). Noninvasive cardiac output measurements provide a dynamic, real-time assessment of hemodynamic parameters. We investigated intradialytic changes in hemodynamic parameters in pediatric outpatients receiving chronic HD and determined patient and treatment risk factors associated with such intradialytic changes. METHODS: Hemodialysis was performed using linear fluid removal over 4 h with polysulfone dialyzers. Continuous wave Doppler ultrasound was used to measure hemodynamic parameters prior, 2 h into, and after the mid-week HD treatment session. Pulse wave tonometry was performed at the same time. The percentage change in blood volume was measured by noninvasive hematocrit monitoring during HD. RESULTS: Twenty-two patients fit the inclusion criteria, of whom 16 (73 %) were male. The mean age of the patients was 17 +/- 3.8 years, and the dialysis vintage was 47.8 +/- 33.7 months. The cardiac index decreased significantly midway through the HD treatment session and remained low until the end of treatment. A significant decline in cardiac index without hypotension occurred in 12 (54 %) patients. Expected increase in systemic vascular resistance index to preserve the cardiac index was not observed. Weight, percentage fluid overload, dialysis vintage, and adequacy did not correlate with the observed decline in the cardiac index. The decrease in blood volume at the 2 h (R = 0.43, p = 0.045) and 4 h (R = 0.56, p = 0.007) time points was the only factor associated with cardiac index decline. CONCLUSION: The cardiac index and stroke volume decreased significantly during the HD session. Patients with larger blood volume changes during the first 2 h of HD and at 4 h showed a significant decrease in cardiac index that did not recover at the completion of the HD treatment. Rate of fluid removal was the only significant risk factor for compromised cardiac index during HD. Conventional methods currently used for assisting fluid removal in HD are inadequate to assess hemodynamic changes. PMID- 27553913 TI - 'Idiopathic' Effusions Get a Proper Name. PMID- 27553914 TI - Incarcerated gravid uterus through a rectal prolapse: First case report. PMID- 27553915 TI - WITHDRAWN: Response from original author: Reproducibility of first trimester three-dimensional placental measurements; a methodological issue. AB - The Publisher regrets that this article is an accidental duplication of an article that has already been published, DOI of original article: http://dx.doi.org/10.1016/j.ejogrb.2016.07.485. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27553916 TI - Bladder function and falls in individuals with multiple sclerosis. AB - PURPOSE: To examine the association between bladder function and falls while controlling for mobility in individuals with multiple sclerosis (MS). METHODS: A total of 92 ambulatory individuals with MS (mean age +/- SD = 59.1 +/- 7.3 years, female n = 69) were divided into two groups based on self-reported bladder function (none-mild n = 43 versus moderate-severe n = 49). The main outcome measure was a number of self-reported falls in the previous 3 months. Participants' demographic information (age, type of MS, gender, use of the assistive device) was also collected. The balance was quantified with the Berg balance scale, and walking speed was indexed with the timed 25-foot walk test. Negative binomial regression analysis was used to examine the association between bladder function and falls in individuals with MS while controlling for balance and walking. RESULTS: The median number of self-reported falls in the previous 3 months was 2 (interquartile range, 0-4). The severe bladder dysfunction group was more likely (incidence rate ratio = 1.84) to have a greater number of self reported falls compared to mild bladder dysfunction group when balance and walking were taken into account. CONCLUSION: Bladder dysfunction is related to falls history independently of mobility in individuals with MS. Future research examining whether bladder management programmes have an impact on fall incidence in MS is warranted. Implications for rehabilitation Bladder dysfunction and falls are common health concerns in individuals with multiple sclerosis. Bladder dysfunction was associated with the number of falls in individuals with MS, and this association was independent of mobility. Bladder management should be included in fall prevention strategies in individuals with MS. PMID- 27553917 TI - Transarterial Chemoembolization versus Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma after Resection within Barcelona Clinic Liver Cancer Stage 0/A: A Retrospective Comparative Study. AB - PURPOSE: To compare outcomes of transarterial chemoembolization with radiofrequency (RF) ablation in treatment of recurrent hepatocellular carcinoma (HCC) after resection within Barcelona Clinic Liver Cancer (BCLC) stage 0/A. MATERIALS AND METHODS: From January 2007 to December 2011, 110 consecutive patients with recurrent HCC meeting BCLC stage 0/A criteria underwent transarterial chemoembolization (n = 78; mean tumor size, 1.9 cm +/- 1.0) or RF ablation (n = 32; mean tumor size, 1.9 cm +/- 0.6) as initial treatment. The primary outcome was overall survival (OS). Kaplan-Meier method was used to construct survival curves, which were compared by log-rank test. Prognostic factors for OS were analyzed using univariate and multivariate Cox proportional hazard models. RESULTS: No significant differences between baseline clinical characteristics of the 2 treatment groups were identified. The 1-, 3-, and 5-year OS rates were 89.7%, 61.0%, and 36.6% for the transarterial chemoembolization group and 90.1%, 72.8%, and 60.0% for the RF ablation group. There was no significant difference in OS rates between the groups (P = .159). Subgroup analysis indicated that RF ablation achieved better survival than transarterial chemoembolization among patients <= 55 years old and patients with BCLC stage 0 (P = .036 and P = .045). Multivariate analysis revealed that serum albumin (<= 35 g/L) (hazard ratio = 2.797; 95% confidence interval, 1.366-2.726; P = .005) and alpha-fetoprotein (> 400 ng/mL) (HR = 2.336; 95% CI, 1.210-4.508; P = .011) levels before treatment were 2 significant risk factors for poor prognosis. CONCLUSIONS: Transarterial chemoembolization might provide a similar OS as RF ablation in patients with recurrent BCLC stage A HCC. However, RF ablation could provide better OS in patients with recurrent BCLC stage 0 HCC. PMID- 27553918 TI - Prospective Evaluation of Passive Expansion of Partially Dilated Transjugular Intrahepatic Portosystemic Shunt Stent Grafts-A Three-Dimensional Sonography Study. AB - PURPOSE: To prospectively investigate early expansion kinetics of underdilated self-expanding stent grafts used for transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: Twenty patients (7 female; mean age 66 y; range, 31-80 y) with liver cirrhosis undergoing TIPS creation for variceal bleeding (n = 5), refractory ascites (n = 14), or both (n = 1) with underdilation of 10-mm stent grafts received two-dimensional (2-D) and three-dimensional (3-D) ultrasound (US) examinations immediately after TIPS creation and 1 and 6 weeks later. Orthogonal views of the TIPS within the parenchymal tract were reconstructed from 3-D volume data sets acquired in longitudinal orientation of the stent. 2-D images and reconstructed 3-D images were used for blinded diameter measurements. Measurement technique was validated with intrainterventional plain radiographs with a sizing catheter as the gold standard. Diameter changes over time and interrelations with patient characteristics (null hypothesis: no expansion, no interrelation) were analyzed using a general linear model for repeated measures. RESULTS: After dilation to 8-mm diameter, 2-D and 3-D measurements showed stent recoil (mean diameter 7.7 mm +/- 0.21 and 7.6 mm +/- 0.17, respectively). Diameter increased significantly from initial measurements to measurements at 1 and 6 weeks (2-D, 8.8 mm +/- 0.24 and 9.4 mm +/- 0.15, both P < .001; 3-D, 8.7 mm +/- 0.27 and 9.4 mm +/- 0.11, both P < .001). Validation measurements showed no significant differences between 2-D or 3-D US and gold standard. There were no statistically significant associations between stent expansion and clinical parameters (sex, P = .78; age, P = .82; etiology/grade of cirrhosis, P = .99; indication for TIPS, P = .78, liver stiffness, P = .70). CONCLUSIONS: Underdilated self-expanding stent grafts used for TIPS creation significantly expand within first 6 weeks after intervention. These changes can be noninvasively monitored using 3-D US. PMID- 27553920 TI - Psychiatric Emergencies for Clinicians: Emergency Department Management of Wernicke-Korsakoff Syndrome. PMID- 27553919 TI - Emergency Medicine Management of Sickle Cell Disease Complications: An Evidence Based Update. AB - BACKGROUND: Sickle cell disease (SCD) affects approximately 100,000 individuals in the United States. Due to alterations in the structural conformation of hemoglobin molecules under deoxygenated conditions, patients with SCD are predisposed to numerous sequelae, many of which require acute intervention. OBJECTIVE: Our aim was to provide emergency physicians with an evidence-based update regarding the diagnosis and management of SCD complications. DISCUSSION: SCD patients experience significant morbidity and mortality secondary to cerebrovascular accident, acute chest syndrome, acute vaso-occlusive pain crises, SCD-related multi-organ failure, cholecystitis, acute intrahepatic cholestasis, acute sickle hepatic crisis, acute hepatic sequestration, priapism, and renal disease. Emergency physicians must recognize acute manifestations of SCD in order to deliver timely management and determine patient disposition. CONCLUSIONS: A comprehensive review of the emergency department management of acute SCD complications is provided. Comprehensive understanding of these aspects of SCD can assist physicians in expediting patient evaluation and treatment, thus decreasing the morbidity and mortality associated with this hemoglobinopathy. PMID- 27553921 TI - Psychiatric Emergencies for Clinicians: Emergency Department Diagnosis and Management of Steroid Psychosis. PMID- 27553922 TI - Acute Aortic Dissection Presenting as Bilateral Lower Extremity Paralysis: A Case Report. AB - BACKGROUND: First described by Morgagni in 1761, aortic dissection (AD) is an acute life-threatening and time-sensitive disease process with an increasing mortality approaching 1% for every 1-hour delay in diagnosis within the first 48 hours. Despite continued surgical advancement, overall in-hospital mortality remains significant (27.4%). CASE REPORT: A 56-year-old woman presented to an outlying emergency department with a complaint of isolated lumbar pain associated with right lower extremity paresthesia and paralysis that progressed to the left. Her medical history and a review of symptoms were significant for chronic obstructive pulmonary disease and tobacco abuse. The initial evaluation in the emergency department included laboratory values and a computed tomography scan of the lumbar spine that revealed minimal disease. After transfer to our tertiary care center for an emergent magnetic resonance imaging scan of the lumbar spine, her vital signs were as follows: blood pressure, 176/84 mm Hg; heart rate, 76 beats/min; respiratory rate, 24 breaths/min; afebrile; and oxygen saturation 98% on room air. A repeat examination revealed cold extremities with mottling, bilateral symmetric lower extremity flaccid paralysis, and a loss of pulses and reflexes. She was insensate below the T10 dermatome. Her upper extremities and cranial nerves were normal. She underwent computed tomography angiography, revealing an extensive Stanford type A AD with interim thrombus formation. After successful endograft stenting, she died 24 hours later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Comprising <2% of all ADs, the pathophysiology of paraplegia as the initial presentation of AD is caused by compression of the anterior spinal artery, resulting in ischemia of the spinal cord. Acute AD is a life-threatening medical emergency that requires a high clinical level of suspicion because of its often variable presentation and high incidence of mortality. PMID- 27553923 TI - Dynamic Forecasting Conditional Probability of Bombing Attacks Based on Time Series and Intervention Analysis. AB - In recent years, various types of terrorist attacks occurred, causing worldwide catastrophes. According to the Global Terrorism Database (GTD), among all attack tactics, bombing attacks happened most frequently, followed by armed assaults. In this article, a model for analyzing and forecasting the conditional probability of bombing attacks (CPBAs) based on time-series methods is developed. In addition, intervention analysis is used to analyze the sudden increase in the time-series process. The results show that the CPBA increased dramatically at the end of 2011. During that time, the CPBA increased by 16.0% in a two-month period to reach the peak value, but still stays 9.0% greater than the predicted level after the temporary effect gradually decays. By contrast, no significant fluctuation can be found in the conditional probability process of armed assault. It can be inferred that some social unrest, such as America's troop withdrawal from Afghanistan and Iraq, could have led to the increase of the CPBA in Afghanistan, Iraq, and Pakistan. The integrated time-series and intervention model is used to forecast the monthly CPBA in 2014 and through 2064. The average relative error compared with the real data in 2014 is 3.5%. The model is also applied to the total number of attacks recorded by the GTD between 2004 and 2014. PMID- 27553924 TI - Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study. AB - OBJECTIVES: To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. METHODS: Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. RESULTS: Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. CONCLUSIONS: The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. KEY POINTS: * Heterogeneity is an intrinsic characteristic of tumoral tissue. * Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. * Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. * The quantification helps differentiate malignant from benign urinary bladder tissue. PMID- 27553925 TI - The porta hepatis microcyst: an additional sonographic sign for the diagnosis of biliary atresia. AB - OBJECTIVES: To describe and evaluate an additional sonographic sign in the diagnosis of biliary atresia (BA), the microcyst of the porta hepatis, in comparison with previously described signs. METHODS: Ultrasound performed in 321 infants (mean age 55 days) with cholestasis were retrospectively analyzed. BA was surgically confirmed in 193 patients and excluded in 128. US evaluated gallbladder type (1: normal; 2: consistent with BA; 3: suspicious), triangular cord sign (TCS), microcyst and macrocyst, polysplenia syndrome, portal hypertension, and bile duct dilatation. T test and Pearson chi2 test were used to compare US signs between the two groups, followed by univariate regression analysis. RESULTS: The highest specificity and sensitivity for BA (p < 0.001) were respectively obtained with non-visible gallbladder (100 %-13 %), macrocyst (99 %-10 %), polysplenia (99 %-11 %), microcyst (98 %-20 %), type 2 gallbladder (98 %-34 %), and TCS (97 %-30 %). Combination of signs (macro or microcyst; cyst and no bile duct dilatation; microcyst and/or TCS; type 2 gallbladder and/or cyst) provided better sensitivities (25-49 %) with similar specificities (95-98 %) (p < 0.001). On univariate analysis, the single US signs most strongly associated with BA were polysplenia (odds ratio, OR 16.3), macrocyst (OR 14.7), TCS (OR 13.4) and microcyst (OR 8). CONCLUSIONS: Porta hepatis microcyst is a reliable US sign for BA diagnosis. KEY POINTS: * The porta hepatis microcyst is a specific sign of biliary atresia. * It was found in 31 (16.1 %) of 193 patients with biliary atresia. * Its specificity was 98 % (p < 0.001). * High frequency transducer and color Doppler can show the porta hepatis microcyst. PMID- 27553926 TI - Non-contrast 3D black blood MRI for abdominal aortic aneurysm surveillance: comparison with CT angiography. AB - OBJECTIVES: Management of abdominal aortic aneurysms (AAAs) is based on diameter. CT angiography (CTA) is commonly used, but requires radiation and iodinated contrast. Non-contrast MRI is an appealing alternative that may allow better characterization of intraluminal thrombus (ILT). This study aims to 1) validate non-contrast MRI for measuring AAA diameter, and 2) to assess ILT with CTA and MRI. METHOD: 28 patients with AAAs (diameter 50.7 +/- 12.3 mm) underwent CTA and non-contrast MRI. MRI was acquired at 3 T using 1) a conventional 3D gradient echo (GRE) sequence and 2) a 3D T1-weighted black blood fast-spin-echo sequence. Two radiologists independently measured the AAA diameter. The ratio of signal of ILT and adjacent psoas muscle (ILTr = signalILT/signalMuscle) was quantified. RESULTS: Strong agreement between CTA and non-contrast MRI was shown for AAA diameter (intra-class coefficient > 0.99). Both approaches had excellent inter observer reproducibility (ICC > 0.99). ILT appeared homogenous on CTA, whereas MRI revealed compositional variations. Patients with AAAs >=5.5 cm and <5.5 cm had a variety of distributions of old/fresh ILT types. CONCLUSIONS: Non-contrast 3D black blood MRI provides accurate and reproducible AAA diameter measurements as validated by CTA. It also provides unique information about ILT composition, which may be linked with elevated risk for disease progression. KEY POINTS: * Non contrast MRI is an appealing alternative to CTA for AAA management. * Non contrast MRI can accurately measure AAA diameters compared to CTA. * MRI affords unique characterization of intraluminal thrombus composition. PMID- 27553927 TI - Percutaneous vertebroplasty under local anaesthesia: feasibility regarding patients' experience. AB - OBJECTIVE: Evaluate patients' intraoperative experience of percutaneous vertebroplasty (PV) performed without general anaesthesia in order to assess the feasibility of local anaesthesia and simple analgesic medication as pain control protocol. METHODS: Ninety-five patients who underwent single-site PV were consecutively included in the study between 2011 and 2013. Each procedure was achieved under local anaesthesia and perfusion of paracetamol, tramadol and dolasetron, with combined CT and fluoroscopy guidance. Numeric pain scale (NPS) was collected before, during and after intervention. After intervention, patients were asked to evaluate their experience as "very bad", "bad", "fair", "good" or "very good", independently of the pain. RESULTS: Indications for vertebroplasty were osteopenic fractures (78 %), aggressive angiomas (13 %) and somatic tumours (9 %). In 76 % of cases, patients' experience was described as "very good" (44 %) or "good" (32 %), whereas 19 % described it as "fair" and 5 % as "very bad". Mean operative NPS was 5.5. After intervention, NPS was significantly lower with a decrease of 4.5 points. No differences were found according to the localization, type of lesion, age or sex either in terms of experience or NPS. CONCLUSION: Percutaneous vertebroplasty is feasible under local anaesthesia alone, with a very good or good experience in 76 % of the patients. KEY POINTS: * Vertebroplasty is a first-line therapy for consolidation and pain control of vertebral lesions. * This procedure is commonly performed under general anaesthesia or conscious sedation. * We perform vertebroplasty under local anaesthesia and simple analgesic protocol with acceptable experience. * Percutaneous vertebroplasty can safely be proposed in a fragile population. PMID- 27553928 TI - Acute effect of static exercise in patients with aortic regurgitation assessed by cardiovascular magnetic resonance: role of left ventricular remodelling. AB - OBJECTIVE: In patients with aortic regurgitation (AR), the effect of static exercise (SE) on global ventricular function and AR severity has not been previously studied. METHODS: Resting and SE cardiovascular magnetic resonance (CMR) were prospectively performed in 23 asymptomatic patients with AR. RESULTS: During SE, we observed a decrease in regurgitant volume in both end-diastolic (EDV) and end-systolic (ESV) volume in both ventricles, as well as a slight decrease in LV ejection fraction (EF). Interestingly, responses varied depending on the degree of LV remodelling. Among patients with a greater degree of LV remodelling, we observed a decrease in LVEF (56 +/- 4 % at rest vs 48 +/- 7 % during SE, p = 0.001) as a result of a lower decrease in LVESV (with respect to LVEDV. Among patients with a lower degree of LV remodelling, LVEF remained unchanged. RVEF remained unchanged in both groups. CONCLUSIONS: In patients with AR, SE provoked a reduction in preload, LV stroke volume, and regurgitant volume. In those patients with higher LV remodelling, we observed a decrease in LVEF, suggesting a lower LV contractile reserve. KEY POINTS: * In patients with aortic regurgitation, static exercise reduced preload volume. * In patients with aortic regurgitation, static exercise reduced stroke volume. * In patients with aortic regurgitation, static exercise reduced regurgitant volume. * In patients with greater remodelling, static exercise unmasked a lower contractile reserve. * Effect of static exercise on aortic regurgitation was assessed by cardiac MR. PMID- 27553929 TI - Prospective 1-year follow-up pilot study of CT-guided microwave ablation in the treatment of bone and soft-tissue malignant tumours. AB - PURPOSE: The aims of this work were to assess the feasibility, efficacy, short term outcome and safety of microwave ablation (MWA) in the treatment of malignant musculoskeletal tumours. MATERIALS AND METHODS: Sixteen bone and soft-tissue malignant tumours were prospectively included and were treated by CT-guided MWA. The percentage and size of necrosis of the lesions were measured by contrast enhanced MRI before the procedure and after 1, 3, 6 and 12 months. mRECIST criteria were used to assess tumour response. Procedural success was defined as >=80 % necrosis. Patient pain (as assessed using a numeric visual scale (NVS)) and side effects were noted. RESULTS: Six osteolytic metastases, five osteoblastic metastases and five soft tissue sarcomas were treated. At 1 month, 40 % were treated completely, the percentage of necrosis was 85 +/- 30.4 %, and the success rate was 80 %. At 3, 6 and 12 months the success rate was 80 %, 76.9 % and 63.6 %, respectively. At 12 months, four lesions (36.3 %) still had no recurrence. Mean NVS during the procedure was 3.5 +/- 2.8. One patient had transitory sciatica without neurological deficit that was treated medically. CONCLUSION: CT-guided MWA of bone and soft-tissue malignant tumours is efficient, well tolerated and has good short-term anti-cancer effects. KEY POINTS: * CT guided MWA is efficient in treating musculoskeletal malignant tumours. * This prospective pilot study showed MWA induces high percentages of tumour necrosis. * MWA has good short-term anti-cancer effects. * MWA has healing potential when lesions can be completely necrosed. * CT-guided MWA under equimolar mixture of oxygen-nitrous oxide inhalation is well tolerated. PMID- 27553930 TI - Comparison of videofluoroscopy and impedance planimetry for the evaluation of oesophageal stenosis: a retrospective study. AB - OBJECTIVES: To compare videofluoroscopy that included a tablet test with impedance planimetry (EndoFLIP(r)) for the evaluation of oesophageal stenosis in patients with dysphagia. METHODS: In 56 patients, videofluoroscopic examinations following the transit of a 14-mm tablet were retrospectively reviewed and correlated with impedance planimetry findings, a catheter-based method using impedance planimetry to display the oesophageal diameter estimates. Additional findings assessed were the occurrence of symptoms during tablet passage and evaluation of oesophageal motility. RESULTS: Impaction of the tablet occurred in 31/56 patients; nine showed a moderate delay (2-15 s), three a short delay (<2 s) and 13 no delay of tablet passage. Both methods showed a significant correlation between tablet impaction and oesophageal diameter <15.1 mm, as measured by impedance planimetry (p = 0.035). The feeling of the tablet getting stuck was reported by seven patients, six showing impaction of the tablet (four with an EndoFLIP-diameter < 13 mm, two with a diameter of 13-19 mm) and one showing delayed passage (EndoFLIP diameter of 17 mm). CONCLUSIONS: Videofluoroscopy and impedance planimetry correlate significantly regarding tablet impaction and residual oesophageal lumen. A standardized 14-mm tablet is helpful in demonstrating oesophageal strictures in dysphagic patients. Triggering of subjective symptoms provides valuable information during a videofluoroscopic study. KEY POINTS: * A 14-mm tablet can demonstrate oesophagogastric junction narrowing in patients with dysphagia. * Type of passage of a tablet enables estimation of oesophageal luminal diameter. * Videofluoroscopy and impedance planimetry correlate significantly regarding tablet impaction and residual oesophageal lumen. PMID- 27553931 TI - Magnetic resonance imaging guided transatrial electrophysiological studies in swine using active catheter tracking - experience with 14 cases. AB - OBJECTIVES: To evaluate the feasibility of performing comprehensive Cardiac Magnetic resonance (CMR) guided electrophysiological (EP) interventions in a porcine model encompassing left atrial access. METHODS: After introduction of two femoral sheaths 14 swine (41 +/- 3.6 kg) were transferred to a 1.5 T MR scanner. A three-dimensional whole-heart sequence was acquired followed by segmentation and the visualization of all heart chambers using an image-guidance platform. Two MR conditional catheters were inserted. The interventional protocol consisted of intubation of the coronary sinus, activation mapping, transseptal left atrial access (n = 4), generation of ablation lesions and eventually ablation of the atrioventricular (AV) node. For visualization of the catheter tip active tracking was used. Catheter positions were confirmed by passive real-time imaging. RESULTS: Total procedure time was 169 +/- 51 minutes. The protocol could be completed in 12 swine. Two swine died from AV-ablation induced ventricular fibrillation. Catheters could be visualized and navigated under active tracking almost exclusively. The position of the catheter tips as visualized by active tracking could reliably be confirmed with passive catheter imaging. CONCLUSIONS: Comprehensive CMR-guided EP interventions including left atrial access are feasible in swine using active catheter tracking. KEY POINTS: * Comprehensive CMR guided electrophysiological interventions including LA access were conducted in swine. * Active catheter-tracking allows efficient catheter navigation also in a transseptal approach. * More MR-conditional tools are needed to facilitate left atrial interventions in humans. PMID- 27553932 TI - Gastric cancer: texture analysis from multidetector computed tomography as a potential preoperative prognostic biomarker. AB - OBJECTIVES: To investigate the association between preoperative texture analysis from multidetector computed tomography (MDCT) and overall survival in patients with gastric cancer. METHODS: Institutional review board approval and informed consent were obtained. Fifty-six patients with biopsy-proved gastric cancer were examined by MDCT and treated with surgery. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. The association with survival time was assessed using Kaplan-Meier and Cox analysis. RESULTS: The following parameters were significantly associated with a negative prognosis, according to different thresholds: energy [no filter] - Logarithm of relative risk (Log RR): 3.25; p = 0.046; entropy [no filter] (Log RR: 5.96; p = 0.002); entropy [filter 1.5] (Log RR: 3.54; p = 0.027); maximum Hounsfield unit value [filter 1.5] (Log RR: 3.44; p = 0.027); skewness [filter 2] (Log RR: 5.83; p = 0.004); root mean square [filter 1] (Log RR: - 2.66; p = 0.024) and mean absolute deviation [filter 2] (Log RR: - 4.22; p = 0.007). CONCLUSIONS: Texture analysis could increase the performance of a multivariate prognostic model for risk stratification in gastric cancer. Further evaluations are warranted to clarify the clinical role of texture analysis from MDCT. KEY POINTS: * Textural analysis from computed tomography can be applied in gastric cancer. * Preoperative non-invasive texture features are related to prognosis in gastric cancer. * Texture analysis could help to evaluate the aggressiveness of this tumour. PMID- 27553933 TI - Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis. AB - OBJECTIVES: Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. METHODS: Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. RESULTS: In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). CONCLUSION: These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. KEY POINTS: * Expression of hepatocyte transporters is modified in rats with advanced liver fibrosis. * Kinetic parameters at gadoxetate-enhanced MRI are correlated with hepatocyte transporter expression. * Hepatocyte transport function can be assessed with compartmental analysis of gadoxetate-enhanced MRI. * Compartmental analysis of gadoxetate-enhanced MRI might provide biomarkers in advanced liver fibrosis. PMID- 27553934 TI - Diagnostic performance of MR imaging findings and quantitative values in the differentiation of seromucinous borderline tumour from endometriosis-related malignant ovarian tumour. AB - OBJECTIVES: To evaluate the diagnostic performance of quantitative values and MRI findings for differentiating seromucinous borderline tumours (SMBTs) from endometriosis-related malignant ovarian tumours (MT). METHODS: This retrospective study examined 19 lesions from SMBT and 84 lesions from MT. The following quantitative values were evaluated using receiver-operating characteristic analysis: overall and solid portion sizes, fluid signal intensity (SI), degree of contrast-enhancement, and mean and minimum apparent diffusion coefficient (ADC) values of the solid portion. Two radiologists independently evaluated four MRI findings characteristic of SMBT, fluid SI on the T1-weighted image and SI of the solid portion on diffusion-weighted image. The diagnostic values of these findings and interobserver agreement were assessed. RESULTS: For diagnosing SMBT, the mean ADC value of the solid portion showed the greatest area under the curve (0.860) (cut-off value: 1.31 * 10-3 mm2/s, sensitivity: 1.00, specificity: 0.61). The T2-weighted image (T2WI) high SI solid portion was the most useful finding, with high specificity and interobserver agreement (sensitivity, 0.58; specificity, 0.95-0.96, kappa = 0.96), followed by T2WI low SI core (sensitivity, 0.48-0.63; specificity, 0.98, kappa = 0.68). CONCLUSION: Mean ADC values of the solid portion, T2WI high SI solid portion, and T2WI low SI core were useful for differentiating SMBT from MT. KEY POINTS: * SMBT is a newly categorised ovarian tumour often associated with endometriosis. * Differentiation of SMBT from endometriosis-related malignant ovarian tumour is clinically important. * Diagnostic performances of quantitative values and MRI findings were evaluated. * Mean ADC value of the solid portion was the most useful value. * "T2WI high SI solid portion" was the most useful MRI finding. PMID- 27553935 TI - MR-guided microwave ablation in hepatic tumours: initial results in clinical routine. AB - OBJECTIVES: Evaluation of the technical success, patient safety and technical effectiveness of magnetic resonance (MR)-guided microwave ablation of hepatic malignancies. METHODS: Institutional review board approval and informed patient consent were obtained. Fifteen patients (59.8 years +/- 9.5) with 18 hepatic malignancies (7 hepatocellular carcinomas, 11 metastases) underwent MR-guided microwave ablation using a 1.5-T MR system. Mean tumour size was 15.4 mm +/- 7.7 (7-37 mm). Technical success and ablation zone diameters were assessed by post ablative MR imaging. Technique effectiveness was assessed after 1 month. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). Mean follow-up was 5.8 months +/- 2.6 (1-10 months). RESULTS: Technical success and technique effectiveness were achieved in all lesions. Lesions were treated using 2.5 +/- 1.2 applicator positions. Mean energy and ablation duration per tumour were 37.6 kJ +/- 21.7 (9-87 kJ) and 24.7 min +/- 11.1 (7-49 min), respectively. Coagulation zone short- and long-axis diameters were 31.5 mm +/- 10.5 (16-65 mm) and 52.7 mm +/- 15.4 (27-94 mm), respectively. Two CTCAE-2-complications occurred (pneumothorax, pleural effusion). Seven patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed. CONCLUSIONS: Microwave ablation is feasible under near real-time MR guidance and provides effective treatment of hepatic malignancies in one session. KEY POINTS: * Planning, applicator placement and therapy monitoring are possible without using contrast enhancement * Energy transmission from the generator to the scanner room is safely possible * MR guided microwave ablation provides effective treatment of hepatic malignancies in one session * Therapy monitoring is possible without applicator retraction from the ablation site. PMID- 27553936 TI - Stiffness of benign and malignant prostate tissue measured by shear-wave elastography: a preliminary study. AB - OBJECTIVES: To measure benign and malignant prostate tissue stiffness using shear wave elastography (SWE). METHODS: Thirty consecutive patients underwent transrectal SWE in the axial and sagittal planes before prostatectomy. After reviewing prostatectomy specimens, two radiologists measured stiffness in regions corresponding to cancers, lateral and median benign peripheral zone (PZ) and benign transition zone (TZ). RESULTS: Cancers were stiffer than benign PZ and TZ. All tissue classes were stiffer on sagittal than on axial imaging, in TZ than in PZ, and in median PZ than in lateral PZ. At multivariate analysis, the nature of tissue (benign or malignant; P < 0.00001), the imaging plane (axial or sagittal; P < 0.00001) and the location within the prostate (TZ, median PZ or lateral PZ; P = 0.0065) significantly and independently influenced tissue stiffness. On axial images, the thresholds maximising the Youden index in TZ, lateral PZ and median PZ were respectively 62 kPa, 33 kPa and 49 kPa. On sagittal images, the thresholds were 76 kPa, 50 kPa and 72 kPa, respectively. CONCLUSIONS: SWE can distinguish prostate malignant and benign tissues. Tissue stiffness is influenced by the imaging plane and the location within the gland. KEY POINTS: * Prostate cancers were stiffer than the benign peripheral zone * All tissue classes were stiffer on sagittal than on axial imaging * All tissue classes were stiffer in the transition zone than in the peripheral zone * All tissue classes were stiffer in the median than in the lateral peripheral zone * Taking into account imaging plane and zonal anatomy can improve cancer detection. PMID- 27553937 TI - Multicentre external validation of the BIMC model for solid solitary pulmonary nodule malignancy prediction. AB - OBJECTIVES: To provide multicentre external validation of the Bayesian Inference Malignancy Calculator (BIMC) model by assessing diagnostic accuracy in a cohort of solitary pulmonary nodules (SPNs) collected in a clinic-based setting. To assess model impact on SPN decision analysis and to compare findings with those obtained via the Mayo Clinic model. METHODS: Clinical and imaging data were retrospectively collected from 200 patients from three centres. Accuracy was assessed by means of receiver-operating characteristic (ROC) areas under the curve (AUCs). Decision analysis was performed by adopting both the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS) risk thresholds. RESULTS: ROC analysis showed an AUC of 0.880 (95 % CI, 0.832-0.928) for the BIMC model and of 0.604 (95 % CI, 0.524-0.683) for the Mayo Clinic model. Difference was 0.276 (95 % CI, 0.190-0.363, P < 0.0001). Decision analysis showed a slightly reduced number of false-negative and false-positive results when using ACCP risk thresholds. CONCLUSIONS: The BIMC model proved to be an accurate tool when characterising SPNs. In a clinical setting it can distinguish malignancies from benign nodules with minimal errors by adopting current ACCP or BTS risk thresholds and guiding lesion-tailored diagnostic and interventional procedures during the work-up. KEY POINTS: * The BIMC model can accurately discriminate malignancies in the clinical setting * The BIMC model showed ROC AUC of 0.880 in this multicentre study * The BIMC model compares favourably with the Mayo Clinic model. PMID- 27553938 TI - Volume-based quantification using dual-energy computed tomography in the differentiation of thymic epithelial tumours: an initial experience. AB - OBJECTIVES: To investigate the diagnostic value of dual-energy computed tomography (DECT) in differentiating between low- and high-risk thymomas and thymic carcinomas. MATERIALS: Our institutional review board approved this study, and patients provided informed consent. We prospectively enrolled 37 patients (20 males, mean age: 55.6 years) with thymic epithelial tumour. All patients underwent DECT. For quantitative analysis, two reviewers measured the following tumour parameters: CT attenuation value in contrast Hounsfield units (CHU), iodine-related HU and iodine concentration (mg/ml). Pathological results confirmed the final diagnosis. RESULTS: Of the 37 thymic tumours, 23 (62.2 %) were low-risk thymomas, five (13.5 %) were high-risk thymomas and nine (24.3 %) were thymic carcinomas. According to quantitative analysis, iodine-related HU and iodine concentration were significantly different among low-risk thymomas, high risk thymomas and thymic carcinomas (median: 29.78 HU vs. 14.55 HU vs. 19.95 HU, p = 0.001 and 1.92 mg/ml vs. 0.99 mg/ml vs. 1.18 mg/ml, p < 0.001, respectively). CONCLUSION: DECT using a quantitative analytical method based on iodine concentration measurement can be used to differentiate among thymic epithelial tumours using single-phase scanning. KEY POINTS: * IHU and IC were lower in high risk thymomas/carcinomas than in low-risk thymomas * IHU and IC were lower in advanced-stage thymomas than in early-stage thymomas * Dual-energy CT helps differentiate among thymic epithelial tumours. PMID- 27553939 TI - Low contrast medium-volume third-generation dual-source computed tomography angiography for transcatheter aortic valve replacement planning. AB - PURPOSE: To investigate feasibility, image quality and safety of low-tube voltage, low-contrast-volume comprehensive cardiac and aortoiliac CT angiography (CTA) for planning transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: Forty consecutive TAVR candidates prospectively underwent combined CTA of the aortic root and vascular access route (270 mgI/ml iodixanol). Patients were assigned to group A (second-generation dual-source CT [DSCT], 100 kV, 60 ml contrast, 4.0 ml/s flow rate) or group B (third-generation DSCT, 70 kV, 40 ml contrast, 2.5 ml/s flow rate). Vascular attenuation, noise, signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were compared. Subjective image quality was assessed by two observers. Estimated glomerular filtration (eGFR) at CTA and follow-up were measured. RESULTS: Besides a higher body-mass-index in group B (24.8+/-3.8 kg/m2 vs. 28.1+/-5.4 kg/m2, P=0.0339), patient characteristics between groups were similar (P>=0.0922). Aortoiliac SNR (P=0.0003) was higher in group B. Cardiac SNR (P=0.0003) and CNR (P=0.0181) were higher in group A. Subjective image quality was similar (P>=0.213) except for aortoiliac image noise (4.42 vs. 4.12, P=0.0374). TAVR-planning measurements were successfully obtained in all patients. There were no significant changes in eGFR among and between groups during follow-up (P>=0.302). CONCLUSION: TAVR candidates can be safely and effectively evaluated by a comprehensive CTA protocol with low contrast volume using low-tube-voltage acquisition. KEY POINTS: * Third-generation dual-source CT facilitates low-tube-voltage acquisition. * TAVR planning can be performed with reduced contrast volume and radiation dose. * TAVR-planning CT did not result in changes in creatinine levels at follow-up. * TAVR candidates can be safely evaluated by comprehensive low-tube-voltage CT angiography. PMID- 27553940 TI - Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes. AB - OBJECTIVES: Our aim was to investigate regional difference in brain activities in response to antiepileptic drug (AED) medications in benign epilepsy with central temporal spikes (BECTS) using resting-state functional magnetic resonance imaging (fMRI). METHODS: Fifty-seven patients with BECTS underwent resting-state fMRI scans after receiving either valproic acid (VPA) (n = 15), levetiracetam (LEV) (n = 21), or no medication (n = 21). fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared and were correlated with total doses of AED in the two medicated groups. RESULTS: Compared with patients on no medication, patients receiving either VPA or LEV showed decreased ReHo in the central-temporal region, frontal cortex, and thalamus. In particular, the VPA group showed greater ReHo decrease in the thalamus and milder in cortices and caudate heads compared with the LEV group. In addition, the VPA group demonstrated a negative correlation between ReHo values in the central-temporal region and medication dose. CONCLUSION: Both VPA and LEV inhibit resting-state neural activity in the central-temporal region, which is the main epileptogenic focus of BECTS. VPA reduced brain activity in the cortical epileptogenic regions and thalamus evenly, whereas LEV reduced brain activity predominantly in the cortices. Interestingly, VPA showed a cumulative effect on inhibiting brain activity in the epileptogenic regions in BECTS. KEY POINTS: * Regional differences in brain activity in response to different AEDs in BECTS. * AEDs inhibit resting-state neural activity in epileptogenic and subcortical regions in BECTS. * Valproic acid effect on the cortical epileptogenic regions and thalamus evenly. * Levetiracetam effect seen predominantly in cortices. * Valproic acid has a cumulative effect on inhibiting brain activity in epileptogenic regions. PMID- 27553941 TI - Ultrasound-guided synovial Tru-cut biopsy: indications, technique, and outcome in 111 cases. AB - OBJECTIVE: To investigate the diagnostic performance of ultrasound-guided synovial biopsy. METHODS: Clinical notes, pathology and microbiology reports, ultrasound and other imaging studies of 100 patients who underwent 111 ultrasound guided synovial biopsies were reviewed. Biopsies were compared with the final clinical diagnosis established after synovectomy (n = 43) or clinical/imaging follow-up (n = 57) (mean 30 months). RESULTS: Other than a single vasovagal episode, no complication of synovial biopsy was encountered. One hundred and seven (96 %) of the 111 biopsies yielded synovium histologically. Pathology +/- microbiology findings for these 107 conclusive biopsies comprised synovial tumour (n = 30, 28 %), synovial infection (n = 18, 17 %), synovial inflammation (n = 45, 42 %), including gouty arthritis (n = 3), and no abnormality (n = 14, 13 %). The accuracy, sensitivity, and specificity of synovial biopsy was 99 %, 97 %, and 100 % for synovial tumour; 100 %, 100 %, and 100 % for native joint infection; and 78 %, 45 %, and 100 % for prosthetic joint infection. False-negative synovial biopsy did not seem to be related to antibiotic therapy. CONCLUSION: Ultrasound-guided Tru-cut synovial biopsy is a safe and reliable technique with a high diagnostic yield for diagnosing synovial tumour and also, most likely, for joint infection. Regarding joint infection, synovial biopsy of native joints seems to have a higher diagnostic yield than that for infected prosthetic joints. KEY POINTS: * Ultrasound-guided Tru-cut synovial biopsy has high accuracy (99 %) for diagnosing synovial tumour. * It has good accuracy, sensitivity, and high specificity for diagnosis of joint infection. * Synovial biopsy of native joints works better than biopsy of prosthetic joints. * A negative synovial biopsy culture from a native joint largely excludes septic arthritis. * Ultrasound-guided Tru-cut synovial biopsy is a safe and well-tolerated procedure. PMID- 27553943 TI - Spatial assessment of soil organic carbon and physicochemical properties in a horticultural orchard at arid zone of India using geostatistical approaches. AB - Soil organic carbon (SOC) is a major indicator of long-term sustenance of agricultural production system. Apart from sustaining productivity, SOC plays a crucial role in context of climate change. Keeping in mind these potentials, spatial variation of SOC contents of a fruit orchard comprising several arid fruit plantations located at arid region of India is assessed in this study through geostatistical approaches. For this purpose, surface and subsurface soil samples from 175 locations from a fruit orchard spreading over 14.33 ha area were collected along with geographical coordinates. SOC content and soil physicochemical properties of collected soil samples were determined followed by geostatistical analysis for mapping purposes. Average SOC stock density of the orchard was 14.48 Mg ha(-1) for 0- to 30-cm soil layer ranging from 9.01 Mg ha( 1) in Carissa carandas to 19.52 Mg ha(-1) in Prosopis cineraria block. Range of spatial variation of SOC content was found about 100 m, while two other soil physicochemical properties, e.g., pH and electrical conductivity (EC) also showed similar spatial trend. This indicated that minimum sampling distance for future SOC mapping programme may be kept lower than 100 m for better accuracy. Ordinary kriging technique satisfactorily predicted SOC contents (in percent) at unsampled locations with root-mean-squared residual (RMSR) of 0.35-0.37. Co-kriging approach was found slightly superior (RMSR = 0.26-0.28) than ordinary kriging for spatial prediction of SOC contents because of significant correlations of SOC contents with pH and EC. Uncertainty of SOC estimation was also presented in terms of 90 % confidence interval. Spatial estimates of SOC stock through ordinary kriging or co-kriging approach were also found with low uncertainty of estimation than non-spatial estimates, e.g., arithmetic averaging approach. Among different fruit block plantations of the orchard, the block with Prosopis cineraria ('khejri') has higher SOC stock density than others. PMID- 27553942 TI - Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer. AB - Evidence gleaned from recent studies on the role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is not only a genetic disease but also an immunologic disease. Head and Neck Squamous Cell Carcinoma (HNSCC) has been a significant model to study cancer cell-immune cell interactions. First, immune cell infiltration is an important feature of these tumors. Second, HNSCC frequently develops resistance to immunogenic cytotoxicity, which provides a window to decipher how tumors engage the immune system to establish immune tolerance. Finally, chemoradiation therapy, as a central modality for HNSCC treatment, has been shown to elicit immune activation. The presence of effector immune cells in the tumor microenvironment is often associated with superior clinical response to adjuvant therapy. On the other hand, an activated immune system, in addition to limiting tumor initiation and progression, could also exert selective pressure to promote the growth of less immunogenic tumors, as a pivotal immunoediting process. But it remains unclear how cancer cell signaling regulates tumor immunogenicity and how to mitigate HNSCC-potentiated TIL suppression. In this review, we will revisit the prognostic role of TILs in HNSCC, and collectively discuss how cancer cell machinery impacts upon the plasticity of TILs. PMID- 27553944 TI - Phytoplankton abundance and structure as indicator of water quality in the drainage system of the Burullus Lagoon, southern Mediterranean coast, Egypt. AB - This study represents the first detailed account of phytoplankton community structure and seasonal succession in eight drain sites and the Brimbal Canal influx into the Burullus Lagoon. The phytoplankton characteristics were studied based on the data collected seasonally over 4 years, from summer 2012 to spring 2016. Various indices such as Palmer's and Shannon's biotic indices were used for the assessment of the water quality of the different drains. There were a total of 194 species belonging to 65 genera and 6 groups: Bacillariophyceae (76 species), Chlorophyceae (59 species), Cyanophyceae (30 species), Euglenophyceae (25 species), Dinophyceae (3 species), and Xanthophyceae (1 species). The phytoplankton community was dominated with diatoms, green algae, and euglenoids such as Cyclotella, Scenedesmus, Navicula, Nitzschia, Ankistrodesmus, Chlorella, and Euglena. Maximum and minimum phytoplankton abundance was recorded at the Brimbal Canal and Hooks Drain. Maximum and minimum species diversities (H') were found at the Hooks Drain (2.564) and Burullus Drain (2.055). Species evenness fluctuated between 0.595 (Burullus Drain) and 0.750 (West Burullus Drain). The total score of algal genus pollution index and the algal species pollution index at the different drains showed that Drain 7 and the West Burullus Drain had moderate pollution, and the total score of the other drains were greater than 20 indicating the confirmed high organic pollution. Thus, the present investigation can be considered an attempt to use the phytoplankton community as a bioindicator of organic pollution. PMID- 27553945 TI - Risk of fire occurrence in arid and semi-arid ecosystems of Iran: an investigation using Bayesian belief networks. AB - Identifying areas that have a high risk of burning is a main component of fire management planning. Although the available tools can predict the fire risks, these are poor in accommodating uncertainties in their predictions. In this study, we accommodated uncertainty in wildfire prediction using Bayesian belief networks (BBNs). An influence diagram was developed to identify the factors influencing wildfire in arid and semi-arid areas of Iran, and it was populated with probabilities to produce a BBNs model. The behavior of the model was tested using scenario and sensitivity analysis. Land cover/use, mean annual rainfall, mean annual temperature, elevation, and livestock density were recognized as the main variables determining wildfire occurrence. The produced model had good accuracy as its ROC area under the curve was 0.986. The model could be applied in both predictive and diagnostic analysis for answering "what if" and "how" questions. The probabilistic relationships within the model can be updated over time using observation and monitoring data. The wildfire BBN model may be updated as new knowledge emerges; hence, it can be used to support the process of adaptive management. PMID- 27553946 TI - Residue levels and discharge loads of antibiotics in wastewater treatment plants (WWTPs), hospital lagoons, and rivers within Lake Victoria Basin, Kenya. AB - The detection of antibiotics in water systems has instigated great environmental concern due to the toxicological effects associated with these compounds. Their discharge into the environment results from the ubiquity of use in medical, veterinary, and agricultural practices. Some of the effects of antibiotics include development of antibiotic-resistant bacteria, making it difficult to treat diseases, variation in natural microbial communities, and enzyme activities. In this study, the first comprehensive survey of some frequently used antibiotics namely ampicillin (AMP), amoxicillin (AMX), sulfamethoxazole (SMX), chloramphenicol (CAP), and ciprofloxacin (CPF) within Lake Victoria Basin of Kenya is presented. Sludge and wastewater samples were collected from wastewater treatment plants (WWTPs) and hospital lagoons within the study area. Samples were extracted and cleaned by solid-phase extraction, and analysis was carried out using high-performance liquid chromatography (HPLC). All wastewater samples and sludge collected contained quantifiable levels of the selected antibiotics. The highest concentrations were recorded for AMP with WWTPs and hospitals having 0.36 +/- 0.04 and 0.79 +/- 0.07 MUg/L, respectively. In sludge samples, SMX recorded the highest concentrations of 276 +/- 12 ng/g. The high levels in sludge indicate the preferential partition of antibiotics onto solid phase, posing great danger to consumers of crops grown in biosolid-amended soils. The daily discharge loads of antibiotics from nine WWTPs ranged between 80.75 and 3044.9 mg day(-1) with a total discharge of 6395.85 mg day(-1), signifying a high potential of water resource pollution within the region. This report will aid in the assessment of the risks posed by antibiotics released into the environment. PMID- 27553947 TI - Assessment of soil quality parameters using multivariate analysis in the Rawal Lake watershed. AB - Soil providing a wide array of ecosystem services is subjected to quality deterioration due to natural and anthropogenic factors. Most of the soils in Pakistan have poor status of available plant nutrients and cannot support optimum levels of crop productivity. The present study statistically analyzed ten soil quality parameters in five subwatersheds (Bari Imam, Chattar, Rumli, Shahdra, and Shahpur) of the Rawal Lake. Analysis of variance (ANOVA), cluster analysis (CA), and principal component analysis (PCA) were performed to evaluate correlation in soil quality parameters on spatiotemporal and vertical scales. Soil organic matter, electrical conductivity, nitrates, and sulfates were found to be lower than that required for good quality soil. Soil pH showed significant difference (p < 0.05) in mean values at different sampling sites and sampling months indicating that it is affected and determined by land uses and seasons. Pearson correlation revealed a strong positive correlation (r = 0.437) between nitrates and organic matter. Application of principal component analysis resulted in three major factors contributing 76 % of the total variance. For factor 1, temperature, sand, silt, clay, and nitrates had the highest factor loading values (>0.75) and indicated that these were the most influential parameters of first factor or component. Cluster analysis separated five sampling sites into three statistically significant clusters: I (Shahdra-Bari Imam), II (Chattar), and III (Shahpur-Rumli). Among the five sites, Shahdra was found to have good quality soil followed by Bari Imam. The present study illustrated the usefulness of multivariate statistical approaches for the analysis and interpretation of complex datasets to understand variations in soil quality for effective watershed management. PMID- 27553948 TI - Fiber-based monolithic columns for liquid chromatography. AB - Fiber-based monoliths for use in liquid chromatographic separations are defined by columns packed with aligned fibers, woven matrices, or contiguous fiber structures capable of achieving rapid separations of proteins, macromolecules, and low molecular weight components. A common denominator and motivating driver for this approach, first initiated 25 years ago, was reducing the cost of bioseparations in a manner that also reduced residence time of retained components while achieving a high ratio of mass to momentum transfer. This type of medium, when packed into a liquid chromatography column, minimized the fraction of stagnant liquid and resulted in a constant plate height for non adsorbing species. The uncoupling of dispersion from eluent flow rate enabled the surface chemistry of the stationary phase to be considered separately from fluid transport phenomena and pointed to new ways to apply chemistry for the engineering of rapid bioseparations. This paper addresses developments and current research on fiber-based monoliths and explains how the various forms of this type of chromatographic stationary phase have potential to provide new tools for analytical and preparative scale separations. The different stationary phases are discussed, and a model that captures the observed constant plate height as a function of mobile phase velocity is reviewed. Methods that enable hydrodynamically stable fiber columns to be packed and operated over a range of mobile phase flow rates, together with the development of new fiber chemistries, are shown to provide columns that extend the versatility of liquid chromatography using monoliths, particularly at the preparative scale. Graphical Abstract Schematic representation of a sample mixture being separated by a rolled stationary phase column, resulting separated peaks shown in the chromatogram. PMID- 27553949 TI - SFC-MS/MS as an orthogonal technique for improved screening of polar analytes in anti-doping control. AB - HPLC is considered the method of choice for the separation of various classes of drugs. However, some analytes are still challenging as HPLC shows limited resolution capabilities for highly polar analytes as they interact insufficiently on conventional reversed-phase (RP) columns. Especially in combination with mass spectrometric detection, limitations apply for alterations of stationary phases. Some highly polar sympathomimetic drugs and their metabolites showed almost no retention on different RP columns. Their retention remains poor even on phenylhexyl phases that show different selectivity due to pi-pi interactions. Supercritical fluid chromatography (SFC) as an orthogonal separation technique to HPLC may help to overcome these issues. Selected polar drugs and metabolites were analyzed utilizing SFC separation. All compounds showed sharp peaks and good retention even for the very polar analytes, such as sulfoconjugates. Retention times and elution orders in SFC are different to both RP and HILIC separations as a result of the orthogonality. Short cycle times could be realized. As temperature and pressure strongly influence the polarity of supercritical fluids, precise regulation of temperature and backpressure is required for the stability of the retention times. As CO2 is the main constituent of the mobile phase in SFC, solvent consumption and solvent waste are considerably reduced. Graphical Abstract SFC-MS/MS vs. LC-MS/MS. PMID- 27553950 TI - Improved parenting maintained four years following a brief parent training intervention in a non-clinical sample. AB - BACKGROUND: The aim of the present study is to evaluate whether the effects of a short, six session version of an evidence-based parent training programme (The Incredible Years), delivered in a non-clinical community sample in the northern Norway, are maintained 4 years following the initial intervention. METHOD: Data were collected primarily from mothers in a randomized controlled trial (N = 117). Children's mean age at 4 year follow-up was 7.5 years. RESULTS: A mixed model analyses of linear change with a time by condition interaction revealed that statistically significant differences were maintained between the parent training and control groups for several outcomes. The parent training group showed a reduction in harsh disciple and an increase of both self-reported positive parenting and parental efficacy when compared to the control group who received services as usual. No significant differences between the two groups were found for child behaviour problems as measured by the ECBI Intensity scale. In addition, mixed model analyses of quadratic change were conducted to test the differences in the trajectory of change over four time points. There were significant differences in the trajectory of change for (1) the ECBI with the parent training group showing an immediate drop in the intensity of problem behaviour and (2) the positive parenting scale showing an immediate steep increase; no other significant differences in trajectory were detected. CONCLUSIONS: Families from a non-clinical sample who participated in a brief version of the Incredible Years Basic parent training programme maintained changes in positive parenting, harsh discipline, and parental efficacy 4 years after completion of the intervention. TRIAL REGISTRATION: ClinicalTrials. gov NCT02850510 . Retrospectively registered 29 July 2016. PMID- 27553951 TI - Molecular Characterization of Invasive Carbapenem-Resistant Acinetobacter baumannii from a Tertiary Care Hospital in South India. AB - INTRODUCTION: Acinetobacter baumannii is an important opportunistic pathogen responsible for causing nosocomial infections. Carbapenems are considered to be the drug of choice to treat infections caused by multidrug-resistant A. baumannii. The prevalent mechanism of carbapenem resistance in A. baumannii is enzymatic degradation by beta-lactamases. Therefore, the aim of the study is to determine the prevalence and distribution of molecular determinants among the clinical isolates of carbapenem-resistant A. baumannii. METHODS: A total of 103 consecutive, non-duplicate carbapenem-resistant A. baumannii isolated from blood and endotracheal aspirates (ETAs) were included in the study. The CarbAcineto NP test was performed for the screening of carbapenemase production. Polymerase chain reaction (PCR) was performed to detect extended spectrum beta-lactamases (ESBLs), metallo-beta-lactamases (MBLs) and oxacillinases (OXAs). PCR was done for the detection of ISAba1 elements, and mapping PCR was performed to identify the position of ISAba1 with respect to the OXA-23-like gene. RESULTS: Among the 103 A. baumannii isolates, 94 were phenotypically identified as carbapenemase producers. blaPER was the most common among the ESBLs. Among MBLs, blaNDM was predominant followed by the blaVIM gene. blaOXA-51 and blaOXA-23 were the most common and present in all 103 isolates. Almost 80% of the isolates had ISAba1 upstream blaOXA-23 gene. CONCLUSION: The blaOXA-23 and blaNDM genes are the most common type of oxacillinases and metallo beta-lactamases, respectively, and contribute to carbapenem resistance in clinical isolates of A. baumannii. The presence of ISAba1 upstream of the blaOXA-23 gene suggests that the insertion element acts as a promoter for its increased expression. FUNDING: Indian Council of Medical Research, New Delhi, India (ref. no. AMR/TF/54/13ECDHII dated 23 October 2013). PMID- 27553953 TI - Role of the Colletotrichum acutatum sesquiterpene synthase CaTPS in the biosynthesis of sesquiterpenoids. AB - Colletotrichum acutatum is a major fungal pathogen of fruit crops, which causes severe yield losses in strawberry production. A potential key factor in plant pathogen interactions is fungal sesquiterpenoids which have mycotoxic and phytotoxic activities. The first committed step in sesquiterpenoid biosynthesis is performed by sesquiterpene synthases (TPS). Only a few TPSs have been functionally characterized from filamentous fungi and none from the genus Colletotrichum. Despite being an important fungal pathogen to agriculture, it is poorly understood at the molecular and chemical levels. The terpenoid biochemistry in Coll. acutatum strain SA 0-1 was studied and one Coll. acutatum TPS (CaTPS) was successfully cloned and characterized in yeast. CaTPS catalyses the biosynthesis of multiple sesquiterpenoids. The two major products are beta caryophyllene and an unidentified sesquiterpenoid along with alpha-humulene as one of the minor sesquiterpenoid products. These products were also secreted by the fungus in strawberry fruit medium along with several other sesquiterpenoids indicating other TPSs are active during in vitro growth. beta-Caryophyllene and alpha-humulene are known cytotoxic products important for ecological interactions and are produced by SA 0-1. Interestingly, a gene expression analysis using quantitative real-time PCR revealed a significant increase in expression of CaTPS during strawberry fruit infection, thus indicating that it could be involved in fruit infection. This is, we believe, the first characterization of TPS in Colletotrichum spp. and terpenoid profiles of Coll. acutatum, which could facilitate studies on the role of terpenoids in the ecology of Coll. acutatum. PMID- 27553952 TI - Use of Causal Diagrams to Inform the Design and Interpretation of Observational Studies: An Example from the Study of Heart and Renal Protection (SHARP). AB - Observational studies often seek to estimate the causal relevance of an exposure to an outcome of interest. However, many possible biases can arise when estimating such relationships, in particular bias because of confounding. To control for confounding properly, careful consideration of the nature of the assumed relationships between the exposure, the outcome, and other characteristics is required. Causal diagrams provide a simple graphic means of displaying such relationships, describing the assumptions made, and allowing for the identification of a set of characteristics that should be taken into account (i.e., adjusted for) in any analysis. Furthermore, causal diagrams can be used to identify other possible sources of bias (such as selection bias), which if understood from the outset, can inform the planning of appropriate analyses. In this article, we review the basic theory of causal diagrams and describe some of the methods available to identify which characteristics need to be taken into account when estimating the total effect of an exposure on an outcome. In doing so, we review the concept of collider bias and show how it is inappropriate to adjust for characteristics that may be influenced, directly or indirectly, by both the exposure and the outcome of interest. A motivating example is taken from the Study of Heart and Renal Protection, in which the relevance of smoking to progression to ESRD is considered. PMID- 27553954 TI - Investigating the role of adipokines in chronic migraine. AB - Background and aims Adiponectin, leptin, and resistin are adipocyte-derived secretory factors involved in endothelial function, weight, inflammation, and insulin resistance. Recent studies suggested a role for adipokines in episodic migraine as mediators of inflammatory processes. The aim of this study was to investigate plasma concentrations of adiponectin, leptin, and resistin in patients with chronic migraine. Materials and methods Twenty-seven chronic migraineurs (20 females, 7 males; mean age 49.0 +/- 9.0 yrs) and 37 healthy controls (23 females, 14 males; mean age 49.8 +/- 15.0 yrs) were selected for the study. Fasting plasmatic levels of total adiponectin, leptin, and resistin were measured using ELISA kits during a pain-free period. Fasting glucose, insulin, total and HDL-cholesterol, triglycerides, and ESR were also determined. Results Serum levels of adiponectin and resistin were significantly increased in chronic migraineurs in comparison with controls ( p = 0.001 and p = 0.032, respectively). After correction for BMI, sex and age, leptin levels were significantly increased in chronic migraineurs ( p = 0.007). A positive correlation between leptin concentrations and both indices of insulin resistance and markers of inflammation was found. Discussion Our data suggest that adiponectin and resistin are altered in non-obese chronic migraineurs. Further studies are needed to elucidate the neurobiological mechanisms underlying adipokine dysfunction in migraine. PMID- 27553955 TI - Measurement properties of tools measuring mental health knowledge: a systematic review. AB - BACKGROUND: Mental health literacy has received great attention recently to improve mental health knowledge, decrease stigma and enhance help-seeking behaviors. We conducted a systematic review to critically appraise the qualities of studies evaluating the measurement properties of mental health knowledge tools and the quality of included measurement properties. METHODS: We searched PubMed, PsycINFO, EMBASE, CINAHL, the Cochrane Library, and ERIC for studies addressing psychometrics of mental health knowledge tools and published in English. We applied the COSMIN checklist to assess the methodological quality of each study as "excellent", "good", "fair", or "indeterminate". We ranked the level of evidence of the overall quality of each measurement property across studies as "strong", "moderate", "limited", "conflicting", or "unknown". RESULTS: We identified 16 mental health knowledge tools in 17 studies, addressing reliability, validity, responsiveness or measurement errors. The methodological quality of included studies ranged from "poor" to "excellent" including 6 studies addressing the content validity, internal consistency or structural validity demonstrating "excellent" quality. We found strong evidence of the content validity or internal consistency of 6 tools; moderate evidence of the internal consistency, the content validity or the reliability of 8 tools; and limited evidence of the reliability, the structural validity, the criterion validity, or the construct validity of 12 tools. CONCLUSIONS: Both the methodological qualities of included studies and the overall evidence of measurement properties are mixed. Based on the current evidence, we recommend that researchers consider using tools with measurement properties of strong or moderate evidence that also reached the threshold for positive ratings according to COSMIN checklist. PMID- 27553956 TI - Mapping adolescent first births within three east African countries using data from Demographic and Health Surveys: exploring geospatial methods to inform policy. AB - BACKGROUND: Early adolescent pregnancy presents a major barrier to the health and wellbeing of young women and their children. Previous studies suggest geographic heterogeneity in adolescent births, with clear "hot spots" experiencing very high prevalence of teenage pregnancy. As the reduction of adolescent pregnancy is a priority in many countries, further detailed information of the geographical areas where they most commonly occur is of value to national and district level policy makers. The aim of this study is to develop a comprehensive assessment of the geographical distribution of adolescent first births in Uganda, Kenya and Tanzania using Demographic and Household (DHS) data using descriptive, spatial analysis and spatial modelling methods. METHODS: The most recent Demographic and Health Surveys (DHS) among women aged 20 to 29 in Tanzania, Kenya, and Uganda were utilised. Analyses were carried out on first births occurring before the age of 20 years, but were disaggregated in to three age groups: <16, 16/17 and 18/19 years. In addition to basic descriptive choropleths, prevalence maps were created from the GPS-located cluster data utilising adaptive bandwidth kernel density estimates. To map adolescent first birth at district level with estimates of uncertainty, a Bayesian hierarchical regression modelling approach was used, employing the Integrated Nested Laplace Approximation (INLA) technique. RESULTS: The findings show marked geographic heterogeneity among adolescent first births, particularly among those under 16 years. Disparities are greater in Kenya and Uganda than Tanzania. The INLA analysis which produces estimates from smaller areas suggest "pockets" of high prevalence of first births, with marked differences between neighbouring districts. Many of these high prevalence areas can be linked with underlying poverty. CONCLUSIONS: There is marked geographic heterogeneity in the prevalence of adolescent first births in East Africa, particularly in the youngest age groups. Geospatial techniques can identify these inequalities and provide policy-makers with the information needed to target areas of high prevalence and focus scarce resources where they are most needed. PMID- 27553957 TI - Trends in axillary treatment for breast cancer patients undergoing sentinel lymph node biopsy as determined by a questionnaire from the Japanese Breast Cancer Society. AB - BACKGROUND: Sentinel lymph node biopsy (SLNB) alone has been compared with SLNB followed by axillary lymph node dissection (ALND) in sentinel lymph node (SLN) positive breast cancer patients in randomized phase III trials: the addition of ALND did not further improve the patient's outcome. However, there is still some controversy, regarding the clinical application of SLNB alone. To identify the optimal axillary treatment in the era of SLNB, the Japanese Breast Cancer Society conducted a group study of SLNB in 2014. METHODS: A questionnaire on axillary surgery and radiation therapy was sent to 432 Japanese institutes in December 2014, and 309 (72 %) completed the questionnaire. RESULTS: SLNB was performed at 98 % of the institutes, and 77 % offered irradiation for cancer treatment. Regarding breast-conserving surgery (BCS), SLNB alone was indicated at 41 % of the institutes in the cases of SLN with micrometastases. However, in the cases of SLN with macrometastases, ALND was performed at 64 %. The proportion of ALND seemed to be higher in total mastectomy than in BCS regardless of the SLN positive status. In the cases of SLN with micrometastases, the radiation field was localized in the conserved breast at about half of the institutes. On the other hand, in the cases of SLN with macrometastases, it was extended to axillary and/or supraclavicular lesions beyond the conserved breast at about 70 % of the institutes. CONCLUSIONS: Japanese breast physicians were conservative with respect to the omission of ALND in SLN-positive breast cancer, especially in the cases of SLN with macrometastases. PMID- 27553958 TI - Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer. AB - BACKGROUND: The Notch receptor plays an important role in various cell fate decisions during development and in cancer. We have previously reported that Notch3 is upregulated by radiation in non-small cell lung cancer (NSCLC) cell lines and that the Notch pathway inhibitor gamma secretase inhibitor GSI (gamma secretase inhibitor), when combined with radiation therapy, significantly suppressed the growth of lung cancer cells. However, little is known about the mechanism of Notch upregulation induced by radiation. Based on reports of Notch expression being activated through the hypoxia inducible factor 1 (HIF-1) under hypoxic conditions, we hypothesized that HIF-1 would be involved in radiation induced Notch activation in NSCLC. METHODS: Changes in HIF-1 and Notch expression in two Notch expressing NSCLC cells line after radiation treatment were examined using Western blotting. Notch expression was evaluated after the suppression of HIF-1alpha by small interfering RNA. The cytotoxic effect of YC-1, a HIF inhibitor, GSI and radiation was examined using the MTT assay in vitro and the xenograft model. RESULT: We found radiation-induced expression of HIF-1alpha protein at 2-6 h after treatment and upregulated expression of Notch3 protein at 24 h after treatment under hypoxic conditions. Specific suppression of HIF-1alpha expression downregulated the radiation-induced Notch3 activation, suggesting that the Notch pathway is activated though HIF-1alpha after radiation. An antitumor effect of YC-1 was evident under hypoxic conditions only when there was simultaneous radiation treatment. GSI and YC-1 had a synergistic antitumor effect in vitro, and the combination of GSI and YC-1 showed the greatest radiosensitivity in vivo. CONCLUSION: Radiation-induced upregulation of the Notch pathway and HIF-1alpha protein may be potential therapeutic targets for more effective radiation therapy. PMID- 27553959 TI - Influence of the agrochemicals used for rice and vegetable cultivation on insecticide resistance in malaria vectors in southern Cote d'Ivoire. AB - BACKGROUND: Vector control can contribute to the development of resistance to insecticides in malaria vectors. As the swamps and wetlands used for some agricultural activities constitute productive breeding sites for many mosquito species, agricultural pest control may increase the selection pressure for insecticide resistance in mosquitoes. Understanding the use of agrochemicals by farmers is important to plan and initiate effective integrated pest and vector management interventions. METHODS: A knowledge-attitude-practice study, using questionnaires, was undertaken with 102 rice farmers in Tiassale and 106 vegetable farmers in Dabou (South Cote d'Ivoire) in order to generate information on pesticide usage. In addition, insecticide susceptibility bioassays were conducted using adult mosquitoes obtained from larvae collected within farms, and the persistence of agricultural pesticides in the farming environment, including sediment and mosquito breeding site water, was investigated by HPLC. RESULTS: Herbicides and insecticides appeared to be the most frequently used pesticides for both crops. Amino phosphonates (mostly glyphosate) represented the most used herbicides (45 % for rice up to 89 % for vegetables). Pyrethroids appeared to be the most used insecticides (accounting for 90 % of all the insecticide use reported). Approximately 75 % of respondents had not been to school and do not understand product labels. Only about 45 % of farmers respect the recommended pesticide dosage and about 10-15 % of pesticides used for rice and vegetable, respectively, are not recommended for these crops. As per WHO criteria, the mosquito local populations from the two localities were resistant to three of the four insecticides tested, as mortalities were less than 35 % for deltamethrin, DDT and bendiocarb. Higher susceptibility was observed for malathion, although the population was considered resistant in Dabou (80 % mortality) and susceptible in Tiassale (98 % mortality). With the exception of glyphosate, residues from each of six chemicals tested for were detected in each of the sites visited in the two localities. CONCLUSION: The study describes the use of insecticides and herbicides on crops and highlights the importance of considering agriculture practices when attempting to manage resistance in malaria vectors. Inter-sectoral collaboration between agriculture and public health is required to develop efficient integrated pest and vector management interventions. PMID- 27553960 TI - Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics. AB - BACKGROUND: Traditional fermented cheese whey (TFCW), containing probiotics, has been used both as a dairy food with ethnic flavor and a medicine for cardiovascular disease, especially regulating blood lipid among Kazakh. We therefore investigated anti-atherosclerotic effects of TFCW in atherosclerotic rabbits and identified lactic acid bacteria (LAB) and yeasts in TFCW. METHODS: Atherosclerotic rabbits were induced by administration of atherosclerotic diet for 12 weeks and divided randomly into three groups and treated for 4 weeks with Simvastatin (20 mg/kg) or TFCW (25 mg/kg) and (50 mg/kg). In addition, a normal control group and an atherosclerotic group were used for comparison. All drugs were intragastrical administered once daily 10 mL/kg for 4 weeks. Body weight (BW), lipid profiles, C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were tested and theromatous plaques and the number of foam cells and infiltrating fibroblast cells in the thoracic aorta endothelium was evaluated by hematoxylin and eosin stainin. LAB and yeasts were isolated and purified by conventional techniques and identified using morphological and biochemical properties as well as gene sequences analysis. RESULTS: After 4 weeks of treatment, high and low dose TFCW decreased serum TC, TG, LDLC, CRP, VCAM-1 and ICAM-1 (P < 0.05) compared to atherosclerotic group, and increased HDL-C (P < 0.05) compared to normal controls. Histological analysis showed TFCW reduced VCAM-1 expression and formation of atheromatous plaques on the aortic endothelium of atherosclerotic rabbits. CONCLUSION: Seven classes of LBA from two different genera including Lactobacillus brevis, Lactobacillus kefianofaciens, Lactobacillus helveticus, Lactobacillus Casei, Lactobacillus plantarum, Lactobacillus kefiri and Lactococcus lactic as well as 2 classes of yeasts from two different genera including Saccharomyces unisporus and Issatchenkia orientalis were isolated and identified from TFCW. In summary, TFCW, containing 7 classes of LBA and 2 classes of yeasts, has significant anti-atherosclerotic potential in atherosclerotic rabbits and may modulate lipid metabolism and protect aorta in the atherosclerotic condition, which might be related to various probiotics acting through reducing the CRP, VCAM-1 and ICAM-1 levels and protecting the aortic endothelium. PMID- 27553961 TI - Skill learning and the evolution of social learning mechanisms. AB - BACKGROUND: Social learning is potentially advantageous, but evolutionary theory predicts that (i) its benefits may be self-limiting because social learning can lead to information parasitism, and (ii) these limitations can be mitigated via forms of selective copying. However, these findings arise from a functional approach in which learning mechanisms are not specified, and which assumes that social learning avoids the costs of asocial learning but does not produce information about the environment. Whether these findings generalize to all kinds of social learning remains to be established. Using a detailed multi-scale evolutionary model, we investigate the payoffs and information production processes of specific social learning mechanisms (including local enhancement, stimulus enhancement and observational learning) and their evolutionary consequences in the context of skill learning in foraging groups. RESULTS: We find that local enhancement does not benefit foraging success, but could evolve as a side-effect of grouping. In contrast, stimulus enhancement and observational learning can be beneficial across a wide range of environmental conditions because they generate opportunities for new learning outcomes. CONCLUSIONS: In contrast to much existing theory, we find that the functional outcomes of social learning are mechanism specific. Social learning nearly always produces information about the environment, and does not always avoid the costs of asocial learning or support information parasitism. Our study supports work emphasizing the value of incorporating mechanistic detail in functional analyses. PMID- 27553963 TI - Tributes to Sr. Marie Simone Roach, Sister of St. Martha of Antigonish, Canada 30th July 1922 to 2nd July 2016. PMID- 27553962 TI - In vitro antibacterial activity of rifampicin in combination with imipenem, meropenem and doripenem against multidrug-resistant clinical isolates of Pseudomonas aeruginosa. AB - BACKGROUND: Multidrug-resistant Pseudomonas aeruginosa has emerged as one of the most important healthcare-associated pathogens. Colistin is regarded as the last resort antibiotic for multidrug-resistant Gram-negative bacteria, but is associated with high rates of acute kidney injury. The aim of this in vitro study is to search for an alternative treatment to colistin for multidrug-resistant P. aeruginosa infections. METHODS: Multidrug and carbapenem-resistant P. aeruginosa isolates were collected between January 2009 and December 2012 at MacKay Memorial Hospital. Minimal inhibitory concentrations (MICs) were determined for various antibiotic combinations. Carbapenemase-producing genes including bla VIM, other beta-lactamase genes and porin mutations were screened by PCR and sequencing. The efficacy of carbapenems (imipenem, meropenem, doripenem) with or without rifampicin was correlated with the type of porin mutation (frameshift mutation, premature stop codon mutation) in multidrug-resistant P. aeruginosa isolates without carbapenemase-producing genes. RESULTS: Of the 71 multidrug-resistant clinical P. aeruginosa isolates, only six harboured the bla VIM gene. Imipenem, meropenem and doripenem were significantly more effective (reduced fold-change of MICs) when combined with rifampicin in bla VIM-negative isolates, especially in isolates with porin frameshift mutation. CONCLUSIONS: Imipenem + rifampicin combination has a low MIC against multidrug-resistant P. aeruginosa, especially in isolates with porin frameshift mutation. The imipenem + rifampicin combination may provide an alternative treatment to colistin for multidrug -resistant P. aeruginosa infections, especially for patients with renal insufficiency. PMID- 27553967 TI - Corrigendum. PMID- 27553968 TI - Does one size fit all? Assessing the preferences of older and younger people for attributes of quality of life. AB - PURPOSE: To systematically compare, via ranking and best worst tasks, the relative importance of key dimensions of quality of life for younger and older people. METHODS: A web-based survey was developed for administration to two Australia-wide community-based samples comprising younger people aged 18-64 years and older people aged 65 years and above. Respondents were asked to rank 12 quality of life dimensions. Respondents also completed a successive best worst task using the same 12 quality of life dimensions. RESULTS: The relative importance of the quality of life dimensions differed for younger and older person samples. For older people, the ability to be independent and to have control over their daily lives were particularly important for their overall quality of life whereas for younger people, mental health was considered most important. CONCLUSIONS: Many interventions accessed by older people in geriatric medicine and aged care sectors have a broader impact upon quality of life beyond health status. The findings from this study indicate that a focus on broader aspects of quality of life may also be consistent with the preferences of older people themselves as to what constitutes quality of life from their perspective. PMID- 27553969 TI - Iridium(III)-Catalyzed Tandem [3 + 2] Annulation: Synthesis of Spirocyclic Phosphoramide Derivatives. AB - A highly efficient iridium(III)-catalyzed C-H activation/tandem Grignard-type [3 + 2] annulation process was developed for the synthesis of novel spirocyclic phosphoramide derivatives. Compared with other transition-metal catalysts, [Cp*IrCl2]2 exhibited favorite efficiency and best selectivity in this cascade reaction. The strategy could be applied to further construct more complex heterocyclic compounds. PMID- 27553970 TI - Fractalkine/CX3CR1 is involved in the pathogenesis of endometriosis by regulating endometrial stromal cell proliferation and invasion. AB - PROBLEM: Chemokines have been reported to play a sovereign role in the establishment and progression of endometriosis. Fractalkine is a chemokine that is upregulated in many inflammatory diseases including endometriosis. Fractalkine functions as a chemotactic role for lymphocytes and monocytes. In this study, we investigated the role of fractalkine/CX3CR1 in the pathogenesis of endometriosis. METHOD OF STUDY: In this study, immunohistochemistry was performed on normal endometrium (taken from controls), eutopic endometrium (taken from patients with endometriosis), and ectopic tissues to analyze fractalkine/CX3CR1 expression. The levels of fractalkine in peritoneal fluid and the cell culture supernatant were examined by enzyme-linked immunosorbent assay (ELISA). Bromodeoxyuridine (BrdU) cell proliferation assay was applied to detect the proliferation of endometrial stromal cells (ESCs). The invasion of ESCs was measured by transwell invasion assay. The protein levels of Bcl2, MMP2, MMP9, p-AKT/AKT, p-p38/p38, p-JNK/JNK, and p-ERK/ERK were analyzed by Western blot. RESULTS: We found that the eutopic endometrium had significantly higher expression of fractalkine and CX3CR1 compared to normal endometrium, and the ectopic tissues had the highest expression. The concentrations of fractalkine in peritoneal fluid of endometriosis patients were obviously higher than that of the control and correlate very well with the severity of endometriosis. Fractalkine enhanced ESCs proliferation and invasion via activating AKT and p38 signal pathways. Moreover, high concentration of estradiol (10(-7) , 10(-6) mol L(-1) ) induced fractalkine expression while high concentration of progesterone (10(-6) , 10(-5) mol L(-1) ) inhibited fractalkine expression in ESCs. CONCLUSION: The results revealed that the high levels of fractalkine in ectopic milieu promoted proliferation and invasion of ESCs through activating AKT and p38 signal pathways. Estradiol has a stimulating effect on the expression of fractalkine. The present results increase our understanding of the significance of fractalkine in the progression of endometriosis and shed some lights on the targeted fractalkine/CX3CR1 therapies. PMID- 27553971 TI - Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism. AB - Autism is a developmental disorder evident from infancy. Yet, its clinical identification requires expert diagnostic training. New evidence indicates disruption to motor timing and integration may underpin the disorder, providing a potential new computational marker for its early identification. In this study, we employed smart tablet computers with touch-sensitive screens and embedded inertial movement sensors to record the movement kinematics and gesture forces made by 37 children 3-6 years old with autism and 45 age- and gender-matched children developing typically. Machine learning analysis of the children's motor patterns identified autism with up to 93% accuracy. Analysis revealed these patterns consisted of greater forces at contact and with a different distribution of forces within a gesture, and gesture kinematics were faster and larger, with more distal use of space. These data support the notion disruption to movement is core feature of autism, and demonstrate autism can be computationally assessed by fun, smart device gameplay. PMID- 27553972 TI - Inspiratory fraction as a marker of skeletal muscle dysfunction in patients with COPD. AB - BACKGROUND: An inspiratory capacity to total lung capacity (IC/TLC) ratio of <=25% has emerged as a better marker of mortality in chronic obstructive pulmonary disease (COPD) patients. The relationship among the IC/TLC ratio to lower extremity skeletal muscle function remains unknown. METHODS: Thirty-five men with moderate to severe COPD were divided into those with IC/TLC<=25% (n=16) and >25% (n=19). The subjects were tested for thigh muscle mass volume (MMT), maximal strength, power output of the lower extremities, and physical activity. RESULTS: Total MMT in the IC/TLC<25% group was significantly lower (413.91+/ 89.42cm3) (p<0.001) than in the IC/TLC>25% group (575.20+/-11.76cm3). In the IC/TLC<=25% group, maximal strength of the lower extremities and muscle peak power output of the lower extremities were 36-56% lower (p<0.01) than among the patients in the IC/TLC>25% group. CONCLUSION: IC/TLC<=25% is associated with reduced maximal strength and peak power output of the lower extremities. IC/TLC<=25% may have an important clinical relevance as an index to determine peripheral muscle dysfunction. PMID- 27553973 TI - Why is viral eradication so important in patients with HCV-related cirrhosis? AB - Approximately one-third of patients infected with chronic HCV have cirrhosis, and this is likely to increase in the near future. The risk of complications, mainly the development of hepatocellular carcinoma, depends on the presence of cirrhosis, and a significant increase in the incidence of cirrhosis-related events, including mortality, is likely in the following years. All-oral therapy with direct-acting antivirals (DAAs) offers a safe and short treatment, with cure rates over 90% in compensated cirrhosis. Cirrhotic patients should be given high priority for treatment because viral clearance has a significant impact on the natural history of HCV infection, halting the progression of the disease and inducing the regression of fibrosis, as well as reducing the need for liver transplantation and improving survival. The benefit of DAAs is great in patients with decompensated cirrhosis, up until recently a population for whom no alternative therapy was available. The efficacy of all-oral therapy has been reported to improve liver function in about 50% of Child-Pugh class C patients. The regression of cirrhosis observed in more than half of patients achieving viral eradication on prior interferon-based regimens still has to be demonstrated in patients treated with DAAs, although there is reason to believe that this will happen. Advanced cirrhosis will eventually become the last boundary of antiviral therapy that will soon be conquered with new drugs currently pending approval. PMID- 27553974 TI - Amiodarone triggers induction of apoptosis in cutaneous leishmaniasis agents. AB - Leishmaniasis is a parasitic disease that is an important problem of public health worldwide. The aim of this study was to assess the cytotoxic effects of amiodarone (AMD) on Leishmania tropica (MHOM/AF/88/KK27) and L. major (MRHO/IR/75/ER) promastigotes and to observe the programmed cell death features. The colorimetric MTT assay was used to find L. tropica and L. major viability and the obtained results were expressed as 50% inhibitory concentration (IC50). Annexin-V FLUOS staining was performed to study the cell death properties of AMD using fluorescence-activated cell-sorting analysis. Qualitative analysis of the total genomic DNA fragmentation was performed by agarose gel electrophoresis. Furthermore, to observe changes in cell morphology, promastigotes were examined using light microscopy. The IC50 was achieved at 55 and 81 MUM for L. tropica and L. major after 48 h of incubation, respectively. In both strains, AMD induced death with features of apoptosis, including externalization of phosphatidylserine, DNA laddering, and cell shrinkage. Our findings indicate that AMD may induce apoptosis on the causative agents of cutaneous leishmaniasis. PMID- 27553975 TI - Evaluation of in vitro and in vivo anti-inflammatory effects of (-) pseudosemiglabrin, a major phytoconstituent isolated from Tephrosia apollinea (Delile) DC. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tephrosia apollinea (Delile) DC (Leguminosae) has been used in folk medicine in Arabian countries to treat inflammatory disorders. The plant has been described to treat swelling, bone fracture, bronchitis, cough, earache and wounds. AIM OF THE STUDY: the current study aims to evaluate the anti inflammatory properties of the major active phytoconstituent of T. apollinea and elucidate the mechanisms by which it inhibits inflammation in vitro and in vivo. MATERIAL AND METHODS: The compound, (-)-pseudosemiglabrin (SSG) was isolated as a major component from the aerial parts of T. apollinea using column chromatography techniques. Sub-chronic in vivo anti-inflammatory effect of SSG was assessed using cotton pellet granuloma assay in SD rats and serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide (NO) were measured, whereas, tail flick assay was performed to assess the analgesic effect of SSG. Furthermore, the anti-inflammatory effects of SSG were confirmed by measuring the levels of IL-1, TNF-alpha, and NO in vitro using human macrophage cell lines (U937). In addition COX inhibition assay was also conducted in cells free system. In silico study was performed to dock SSG in cyclooxygenase enzymes and opioid receptor to predict its structure-activity and molecular mechanism. RESULTS: SSG displayed potential inhibition of granuloma tissue in rats and significantly (P<0.05) lowered the production of cytokines (TNF- alpha and IL-1) in vivo as well as human macrophages. Further investigation revealed that, SSG selectively inhibited COX-2 by 60% with negligible effect on COX-1. The selectivity of SSG towards COX-2 was confirmed in silico wherein, SSG demonstrated significant binding affinity with binding energy (-9.42kcal/mol). The binding found to be through covalent energy with Ser-530 amino acid residue of the active pocket of COX-2. SSG was found to prolong the flick tail time in mice by two folds. Further computational studies reveal that SSG binds to opioid receptor (u-OR) through Ile-144 and Thr-218 with affinity two folds compared to the reference compounds, codeine and aspirin. CONCLUSION: In the present study the major phytoconstituent (-)-pseudosemiglabrin (SSG) from the aerial parts of T. apollinea demonstrated potent anti-inflammatory effect by inhibiting of granuloma tissue in rats and prolonging the tail flick time in mice. Investigation of levels of pro-inflammatory cytokines in SSG-treated rats and human macrophages demonstrated that SSG significantly inhibited TNF-alpha and IL 1. Also SSG showed selective inhibitory effect towards COX-2. In silico study exhibited pronounced binding affinity between SSG and u-opioid receptor better than that of codeine and aspirin. The obtained results justify the use of aerial parts of T. apollinea to treat various inflammatory diseases and indicate that ( )-pseudosemiglabrin has a great potential to be further developed as a promising anti-inflammatory drug. PMID- 27553976 TI - Potent bacterial neuraminidase inhibitors, anthraquinone glucosides from Polygonum cuspidatum and their inhibitory mechanism. AB - ETHNOPHARMACOLOGICAL RELEVANCE: P. cuspidatum is a popular Chinese medicinal herb, having a long history of usage in traditional Chinese medicine for the treatment of several inflammatory diseases in the form of powders and decoctions. Similarly there are many reports that P. cuspidatum has antibacterial and anti inflammatory effects, both of which are properties associated with compounds having activity against bacterial neuraminidase (BNA). AIM OF THE STUDY: We investigated whether P. cuspidatum's metabolites exhibited BNA inhibition. Consistent with our hypothesis, we found several inhibitors from the methanol extract of this plant, and then fully characterized their inhibitory mechanisms. MATERIALS AND METHODS: Activity guided separation of methanol extract led to isolation of individual constituents, and subsequently their structures were elucidated by spectroscopic analysis. Detailed kinetic behaviors of BNA inhibitors were explored by showing the changes of Km and Vmax, the ratios of KI/KIS and Kik/Kiv, and fluorescence quenching effect. RESULTS AND CONCLUSION: This study attempted to isolate the responsible metabolites and elucidate the BNA inhibitory mechanism. The principal BNA inhibitory compounds (2-6) were identified as emodin (2), physcion-8-O-beta-D-glucopyranoside (3), emodin-8-O beta-D-glucopyranoside (4), emodin-1-O-beta-D-glucopyranoside (5), and 2-methoxy 6-acetyl-7-methyljuglone (6). Unexpectedly, anthraquinone glucosides (3-5) were much more potent than their corresponding aglycones (1 and 2). For example, emodin (2) had an IC50=5.4MUM, whereas its glucosides (4 and 5) had IC50=0.85MUM and 0.43MUM respectively. A similar trend was observed with physcion (1, IC50>200MUM) and its glucoside (3, IC50=6.2MUM). The anthraquinone (2) was mixed type I inhibitor, whereas its glucosides (4 and 5) were noncompetitive. In addition, the fluorescence quenching study showed that the affinity constants (KSV) of inhibitors increased in proportion to their inhibitory potencies. Furthermore, we quantified the major and minor metabolites through UPLC-PDA-Q TOF/MS, and revealed that the most potent inhibitors were the major constituents. This result contributes to our understanding of P. cuspidatum utility as functional food stuff and widely used herbal medicine. PMID- 27553978 TI - The effects of Sceletium tortuosum (L.) N.E. Br. extract fraction in the chick anxiety-depression model. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sceletium tortuosum (L.) N.E. Br. has been reported to elevate mood, reduce anxiety and stress and alleviate pain. AIM OF STUDY: This study sought to examine the effects of an S. tortuosum alkaloid enriched fraction in the chick anxiety-depression model, a model that shows high predictive validity as a pharmacological screening assay. MATERIAL AND METHODS: Socially-raised male Silver Laced Wyandotte chicks (4-6 days old) were given IP vehicle, imipramine (10mg/kg), or S. tortuosum fraction (10, 20, 30mg/kg in Exp. 1 or 50, 75, 100mg/kg in Exp. 2) 15min prior to a 60min isolation test period in which distress vocalizations (DVoc) were continuously recorded. RESULTS: Vehicle chicks displayed high DVoc rates in the anxiety phase (first 3min). DVoc rates declined about 50% (i.e., behavioral despair) in the depression phase (30-60min). S. tortuosum fraction at 75 and 100mg/kg decreased DVoc rates during the anxiety phase indicative of an anxiolytic effect. Imipramine, but not S. tortuosum groups, increased DVoc rates in the depression phase indicative of an antidepressant effect. CONCLUSIONS: The findings suggest that an alkaloid enriched S. tortuosum fraction may benefit some forms of stress-related disorders. PMID- 27553979 TI - Mobile Mental Health: Navigating New Rules and Regulations for Digital Tools. AB - Mobile health (mHealth) apps are becoming much more widely available. As more patients learn about and download apps, clinicians are sure to face more questions about the role these apps can play in treatment. Clinicians thus need to familiarize themselves with the clinical and legal risks that apps may introduce. Regulatory rules and organizations that oversee the safety and efficacy of mHealth apps are currently fragmentary in nature and clinicians should pay special attention to categories of apps which are currently exempt from significant regulation. Uniform HIPAA protection does not apply to personal health data that are shared with apps in many contexts which creates a number of clinically relevant privacy and security concerns. Clinicians should also consider several relatively novel potential adverse clinical outcomes and liability concerns that may be relevant to specific categories of apps, including apps that target (i) medication adherence, (ii) collection of self-reported data, (iii) collection of passive data, and (iv) generation of treatment recommendations for psychotherapeutic and behavioral interventions. Considering these potential pitfalls (and disclosing them to patients as a part of obtaining informed consent) is necessary as clinicians consider incorporating apps into treatment. PMID- 27553977 TI - Total saponins of panaxnotoginseng promotes lymphangiogenesis by activation VEGF C expression of lymphatic endothelial cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lymphatic system plays an important role in maintaining the fluid homeostasis and normal immune responses, anatomic or functional obstruction of which leads to lymphedema, and treatments for therapeutic lymphangiogenesis are efficiency for secondary lymphedema. Total saponins of panaxnotoginseng (PNS) are a mixture isolated from Panaxnotoginseng (Burkill) F.H.Chen, which has been used as traditional Chinese medicine in China for treatment of cardio- and cerebro-vascular diseases. The aim of this study was to determine the effect and mechanism of PNS on lymphangiogenesis. METHODS: The Tg (fli1: egfp; gata1: dsred) transgenic zebrafish embryos were treated with different concentrations of PNS (10, 50, 100MUM) for 48h with or without the 6h pretreatment of the 30MUM Vascular endothelial growth factors receptor (VEGFR)-3 kinase inhibitor, followed with morphological observation and lympangiogenesis of thoracic duct assessment. The effect of PNS on cell viability, migration, tube formation and Vascular endothelial growth factors (VEGF)-C mRNA and protein expression of lymphatic endothelial cells (LECs) were determined. The role of phosphatidylinositol-3 (PI-3)-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2 pathways, c-Jun N-terminal kinase (JNK) and P38 mitogen activated protein kinases (MAPK) signaling in PNS-induced VEGF-C expression of LECs by using pharmacological agents to block each signal. RESULTS: PNS promotes lymphangiogenesis of thoracic duct in zebrafish with or without VEGFR3 Kinase inhibitor pre-impairment. PNS promotes proliferation, migration and tube formation of LECs. The tube formation induced by PNS could be blocked by VEGFR3 Kinase inhibitor. PNS induce VEGF-C expression of LEC, which could be blocked by ERK1/2, PI3K and P38MAPK signaling inhibitors. CONCLUSION: PNS activates lymphangiogenesis both in vivo and in vitro by up-regulating VEGF-C expression and activation of ERK1/2, PI3K and P38MAPK signaling. These findings provide a novel insight into the role of PNS in lymphangiogenesis and suggest that it might be an attractive and suitable therapeutic agent for treating secondary lymphedema or other lymphatic system impairment related disease. PMID- 27553981 TI - The Effectiveness of Diaphragmatic Breathing Relaxation Training for Reducing Anxiety. AB - PURPOSE: To evaluate the effectiveness on reducing anxiety of a diaphragmatic breathing relaxation (DBR) training program. DESIGN AND METHODS: This experimental, pre-test-post-test randomized controlled trial with repeated measures collected data using the Beck Anxiety Inventory and biofeedback tests for skin conductivity, peripheral blood flow, heart rate, and breathing rate. FINDINGS: The experimental group achieved significant reductions in Beck Anxiety Inventory scores (p < .05), peripheral temperature (p = .026), heart rate (p = .005), and breathing rate (p = .004) over the 8-week training period. The experimental group further achieved a significant reduction in breathing rate (p < .001). PRACTICE IMPLICATIONS: The findings provide guidance for providing quality care that effectively reduces the anxiety level of care recipients in clinical and community settings. PMID- 27553980 TI - Sleep and Eating Disorders. AB - Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia. PMID- 27553982 TI - Tomato leaf curl New Delhi virus: a widespread bipartite begomovirus in the territory of monopartite begomoviruses. AB - : Tomato leaf curl New Delhi virus (ToLCNDV) is an exceptional Old World bipartite begomovirus. On the Indian subcontinent, a region in which monopartite DNA satellite-associated begomoviruses with mostly narrow geographical ranges predominate, it is widespread, with a geographical range also including the Far East, Middle East, North Africa and Europe. The success of ToLCNDV probably derives from its broad host range and highly flexible genomic configuration: its DNA-A component is capable of productively interacting with, and trans replicating, diverse DNA-B components and betasatellites. An understanding of the capacity of ToLCNDV to infect a variety of hosts and spread across a broad and ecologically variable geographical range could illuminate the potential economic threats associated with similar begomoviral invasions. Towards this end, we used available ToLCNDV sequences to reconstruct the history of ToLCNDV spread. TAXONOMY: Family Geminiviridae, Genus Begomovirus. ToLCNDV is a bipartite begomovirus. Following the revised begomovirus taxonomic criteria of 91% and 94% nucleotide identity for species and strain demarcation, respectively, ToLCNDV is a distinct species with two strains: ToLCNDV and ToLCNDV-Spain. HOST RANGE: The primary cultivated host of ToLCNDV is tomato (Solanum lycopersicum), but the virus is also known to infect 43 other plant species from a range of families, including Cucurbitaceae, Euphorbiaceae, Solanaceae, Malvaceae and Fabaceae. DISEASE SYMPTOMS: Typical symptoms of ToLCNDV infection in its various hosts include leaf curling, vein thickening, puckering, purpling/darkening of leaf margins, leaf area reduction, internode shortening and severe stunting. PMID- 27553983 TI - Hexagonal@Cubic CdS Core@Shell Nanorod Photocatalyst for Highly Active Production of H2 with Unprecedented Stability. AB - A highly effective, low-cost strategy for improved photocatalytic efficiency and stability of CdS is described. Based on the integration of hexagonal-cubic core shell architecture with nanorod morphology, the concentric CdS nanorod phase junctions (NRPJs) obtained demonstrate extremely high H2 production rate and unprecedented photocatalytic stability. PMID- 27553985 TI - Does stapes surgery improve tinnitus in patients with otosclerosis? AB - INTRODUCTION: Otosclerosis (OS) is the primary disease of the human temporal bone characterized by conductive hearing loss and tinnitus. The exact pathogenesis of tinnitus in otosclerosis patients is not known and factors affecting the tinnitus outcome in otosclerosis patients are still controversial. OBJECTIVES: To find the effect of stapedotomy on tinnitus for otosclerosis patients. METHODS: Fifty-six otosclerosis patients with preoperative tinnitus were enrolled to the study. Pure tone average Air-Bone Gap values, preoperative tinnitus pitch, Air-Bone Gap closure at tinnitus frequencies were evaluated for their effect on the postoperative outcome. RESULTS: Low pitch tinnitus had more favorable outcome compared to high pitch tinnitus (p=0.002). Postoperative average pure tone thresholds Air-Bone Gap values were not related to the postoperative tinnitus (p=0.213). There was no statistically significant difference between postoperative Air-Bone Gap closure at tinnitus frequency and improvement of high pitch tinnitus (p=0.427). There was a statistically significant difference between Air-Bone Gap improvement in tinnitus frequency and low pitch tinnitus recovery (p=0.026). CONCLUSION: Low pitch tinnitus is more likely to be resolved after stapedotomy for patients with otosclerosis. High pitch tinnitus may not resolve even after closure of the Air-Bone Gap at tinnitus frequencies. PMID- 27553984 TI - S-Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics. AB - Mammalian cells can utilize hydrogen sulfide (H2S) to support mitochondrial respiration. The aim of our study was to explore the potential role of S sulfhydration (a H2S-induced posttranslational modification, also known as S persulfidation) of the mitochondrial inner membrane protein ATP synthase (F1F0 ATP synthase/Complex V) in the regulation of mitochondrial bioenergetics. Using a biotin switch assay, we have detected S-sulfhydration of the alpha subunit (ATP5A1) of ATP synthase in response to exposure to H2S in vitro. The H2S generator compound NaHS induced S-sulfhydration of ATP5A1 in HepG2 and HEK293 cell lysates in a concentration-dependent manner (50-300MUM). The activity of immunocaptured mitochondrial ATP synthase enzyme isolated from HepG2 and HEK293 cells was stimulated by NaHS at low concentrations (10-100nM). Site-directed mutagenesis of ATP5A1 in HEK293 cells demonstrated that cysteine residues at positions 244 and 294 are subject to S-sulfhydration. The double mutant ATP synthase protein (C244S/C294S) showed a significantly reduced enzyme activity compared to control and the single-cysteine-mutated recombinant proteins (C244S or C294S). To determine whether endogenous H2S plays a role in the basal S sulfhydration of ATP synthase in vivo, we compared liver tissues harvested from wild-type mice and mice deficient in cystathionine-gamma-lyase (CSE, one of the three principal mammalian H2S-producing enzymes). Significantly reduced S sulfhydration of ATP5A1 was observed in liver homogenates of CSE-/- mice, compared to wild-type mice, suggesting a physiological role for CSE-derived endogenous H2S production in the S-sulfhydration of ATP synthase. Various forms of critical illness (including burn injury) upregulate H2S-producing enzymes and stimulate H2S biosynthesis. In liver tissues collected from mice subjected to burn injury, we detected an increased S-sulfhydration of ATP5A1 at the early time points post-burn. At later time points (when systemic H2S levels decrease) S sulfhydration of ATP5A1 decreased as well. In conclusion, H2S induces S sulfhydration of ATP5A1 at C244 and C294. This post-translational modification may be a physiological mechanism to maintain ATP synthase in a physiologically activated state, thereby supporting mitochondrial bioenergetics. The sulfhydration of ATP synthase may be a dynamic process, which may be regulated by endogenous H2S levels under various pathophysiological conditions. PMID- 27553986 TI - Gut microbiota in chronic kidney disease. AB - The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases. In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD. This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications. PMID- 27553987 TI - Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis. AB - BACKGROUND: Testosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin stimulating agents (ESA). METHODS: Single-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. RESULTS: Mean testosterone level was 321+/ 146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753+/-1784 vs. 4291+/-3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. CONCLUSION: Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis. PMID- 27553988 TI - Myasthenia gravis after kidney transplantation. PMID- 27553989 TI - Novel approach to analysing large data sets of personal sun exposure measurements. AB - Personal sun exposure measurements provide important information to guide the development of sun awareness and disease prevention campaigns. We assess the scaling properties of personal ultraviolet radiation (pUVR) sun exposure measurements using the wavelet transform (WT) spectral analysis to process long range, high-frequency personal recordings collected by electronic UVR dosimeters designed to measure erythemal UVR exposure. We analysed the sun exposure recordings of school children, farmers, marathon runners and outdoor workers in South Africa, and construction workers and work site supervisors in New Zealand. We found scaling behaviour in all the analysed pUVR data sets. We found that the observed scaling changes from uncorrelated to long-range correlated with increasing duration of sun exposure. Peaks in the WT spectra that we found suggest the existence of characteristic times in sun exposure behaviour that were to some extent universal across our data set. Our study also showed that WT measures enable group classification, as well as distinction between individual UVR exposures, otherwise unattainable by conventional statistical methods. PMID- 27553990 TI - Probabilistic estimation of residential air exchange rates for population-based human exposure modeling. AB - Residential air exchange rates (AERs) are a key determinant in the infiltration of ambient air pollution indoors. Population-based human exposure models using probabilistic approaches to estimate personal exposure to air pollutants have relied on input distributions from AER measurements. An algorithm for probabilistically estimating AER was developed based on the Lawrence Berkley National Laboratory Infiltration model utilizing housing characteristics and meteorological data with adjustment for window opening behavior. The algorithm was evaluated by comparing modeled and measured AERs in four US cities (Los Angeles, CA; Detroit, MI; Elizabeth, NJ; and Houston, TX) inputting study specific data. The impact on the modeled AER of using publically available housing data representative of the region for each city was also assessed. Finally, modeled AER based on region-specific inputs was compared with those estimated using literature-based distributions. While modeled AERs were similar in magnitude to the measured AER they were consistently lower for all cities except Houston. AERs estimated using region-specific inputs were lower than those using study-specific inputs due to differences in window opening probabilities. The algorithm produced more spatially and temporally variable AERs compared with literature-based distributions reflecting within- and between-city differences, helping reduce error in estimates of air pollutant exposure. PMID- 27553991 TI - Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: The Hokkaido Study. AB - Prenatal exposure to perfluoroalkyl acids (PFAAs) influences fetal growth and long-term health. However, whether PFAAs affect offspring DNA methylation patterns to influence health outcomes is yet to be evaluated. Here, we assessed effect of prenatal PFAA exposure on cord blood insulin-like growth factor 2 (IGF2), H19, and long interspersed element 1 (LINE1) methylation and its associations with birth size. Mother-child pairs (N=177) from the Hokkaido Study on Environment and Children's Health were included in the study. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) levels in maternal serum were measured by liquid chromatography-tandem mass spectrometry. IGF2, H19, and LINE1 methylation in cord blood DNA was determined by pyrosequencing. After full adjustment in multiple linear regression models, IGF2 methylation showed a significant negative association with log-unit increase in PFOA (partial regression coefficient=-0.73; 95% confidence interval: -1.44 to -0.02). Mediation analysis suggested that reduced IGF2 methylation explained ~21% of the observed association between PFOA exposure and reduced ponderal index of the infant at birth. These results indicated that the effects of prenatal PFOA exposure could be mediated through DNA methylation. Further study will be required to determine the potential for long-term adverse health effects of reduced IGF2 methylation induced by PFOA exposure. PMID- 27553993 TI - What does the future hold? The need to engage in discussions around prognosis. PMID- 27553992 TI - Seasonal and occupational trends of five organophosphate pesticides in house dust. AB - Since 1998, the University of Washington's Center for Child Environmental Health Risks Research has followed a community-based participatory research strategy in the Lower Yakima Valley of Washington State to assess pesticide exposure among families of Hispanic farmworkers. As a part of this longitudinal study, house dust samples were collected from both farmworker and non-farmworker households, across three agricultural seasons (thinning, harvest and non-spray). The household dust samples were analyzed for five organophosphate pesticides: azinphos-methyl, phosmet, malathion, diazinon, and chlorpyrifos. Organophosphate pesticide levels in house dust were generally reflective of annual use rates and varied by occupational status and agricultural season. Overall, organophosphate pesticide concentrations were higher in the thinning and harvest seasons than in the non-spray season. Azinphos-methyl was found in the highest concentrations across all seasons and occupations. Farmworker house dust had between 5- and 9 fold higher concentrations of azinphos-methyl than non-farmworker house dust. Phosmet was found in 5-7-fold higher concentrations in farmworker house dust relative to non-farmworker house dust. Malathion and chlorpyriphos concentrations in farmworker house dust ranged between 1.8- and 9.8-fold higher than non farmworker house dust. Diazinon showed a defined seasonal pattern that peaked in the harvest season and did not significantly differ between farmworker and non farmworker house dust. The observed occupational differences in four out of five of the pesticide residues measured provides evidence supporting an occupational take home pathway, in which workers may bring pesticides home on their skin or clothing. Further, these results demonstrate the ability of dust samples to inform the episodic nature of organophosphate pesticide exposures and the need to collect multiple samples for complete characterization of exposure potential. PMID- 27553994 TI - Recent advances in autosomal-dominant polycystic kidney disease. AB - Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD. PMID- 27553995 TI - Corrigendum. PMID- 27553996 TI - Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services. AB - These guidelines, informed by the best available evidence and consensus expert opinion, provide a framework to guide the timely initiation of chemotherapy for treating cancer. They sit at the intersection of patient experience, state-of-the art disease management and rational efficient service provision for these patients at a system level. Internationally, cancer waiting times are routinely measured and publicly reported. In Australia, there are existing policies and guidelines relating to the timeliness of cancer care for surgery and radiation therapy; however, until now, equivalent guidance for chemotherapy was lacking. Timeliness of care should be informed, where available, by evidence for improved patient outcomes. Independent of this, it should be recognised that shorter waiting periods are likely to reduce patient anxiety. While these guidelines were developed as part of a proposed framework for consideration by the Victorian Department of Health, they are clinically relevant to national and international cancer services. They are intended to be used by clinical and administrative staff within cancer services. Adoption of these guidelines, which are for the timely triage, review and treatment of cancer patients receiving systemic chemotherapy, aims to ensure that patients receive care within a timeframe that will maximise health outcomes, and that access to care is consistent and equitable across cancer services. Local monitoring of performance against this guideline will enable cancer service providers to manage proactively future service demand. PMID- 27553997 TI - Normalisation of hypoxaemia following successful percutaneous closure of a bidirectional shunting secundum atrial septal defect without pulmonary hypertension in a patient with severe non-ischaemic cardiomyopathy and refractory ventricular tachycardia. AB - Atrial septal defects (ASD) are an uncommon cause of dyspnoea. A high index of suspicion is required, and further investigation should be prompted in patients with unexplained hypoxaemia, particularly those with pulmonary hypertension. Hypoxic ASD without pulmonary hypertension are rare, and only a handful of cases have been published. We present a middle-aged man with progressive dyspnoea with a successfully closed ASD without pulmonary hypertension caused by elevated right ventricular pressures secondary to an idiopathic cardiomyopathy. PMID- 27553998 TI - A functional magnetic resonance imaging study of the neuronal specificity of an acupoint: acupuncture at Rangu (KI 2) and its sham point. AB - The neuronal specificity of acupoints has not been entirely supported by the results of previous functional magnetic resource imaging studies. This study tested the specificity of an acupoint using right Rangu (KI 2) and its sham acupoint. The results showed specific cerebral response patterns and thus provided the evidence of the existence of acupoint neuronal specificity. PMID- 27553999 TI - Evolving telehealth reimbursement in Australia. AB - Video-based consultation is the only telehealth service reimbursed by the Medicare Benefits Schedule in Australia, but the uptake of telehealth is still low and inconsistent. There is a clear need for the development of appropriate medical evidence to support implementation of telehealth services. With the ubiquitous use of mobile phones, mobile health becomes important in facilitating health services and impacting clinical outcomes anywhere. PMID- 27554000 TI - Characteristics of Queensland physicians and the influence of rural exposure on practice location. AB - The Queensland branch of the Royal Australasian College of Physicians (RACP) commissioned this study to update their workforce profile and examine rural practice. The present investigation aimed to describe characteristics of Queensland physicians and determine the influence of childhood and training locations on current rural practice. A cross-sectional online survey, conducted 4 July-4 November 2013, was administered to Fellows of The RACP, Queensland. Descriptive statistics report characteristics and logistic regression analyses identify associations and interactions. The outcome measure was current practice location using the Australian Standard Geographic Classification - Remoteness Area. Data were obtained for 633 physicians. Their average age was 49.5 years, a third was female and a quarter was in rural practice. Rural practice was associated with a rural childhood (odds ratio (OR) (95% confidence interval, CI) 1.89 (1.10, 3.27) P = 0.02) and any time spent as an intern (OR 4.07 (2.12, 7.82) P < 0.001) or registrar (OR 4.00 (2.21, 7.26) P < 0.001) in a rural location. Physicians with a rural childhood and rural training were most likely to be in rural practice. However, those who had a metropolitan childhood and a rural internship were approximately five times more likely to be working in rural practice than physicians with no rural exposure (OR 5.33 (1.61, 17.60) P < 0.01). The findings demonstrate the positive effect of rural vocational training on rural practice. A prospective study would determine if recent changes to the Basic Physician Training Pathway and the Basic Paediatric Training Network (more rural training than previous pathways) increases the rate of rural practice. PMID- 27554002 TI - Fresh frozen plasma and prothrombin concentrate transfusions in a South Australian teaching hospital: patterns of use and effects on international normalised ratios. PMID- 27554001 TI - An unusual presentation of Miller Fisher syndrome with optic neuropathy. PMID- 27554003 TI - Rheumatoid arthritis heralded by the hypereosinophilic syndrome. PMID- 27554004 TI - Asthma Cycle of Care uptake among Australian older women with asthma. PMID- 27554005 TI - Coronary computed tomographic arteriography is anatomical and a myocardial perfusion study is functional, detecting ischaemia, hence they are complementary. PMID- 27554006 TI - Author reply. PMID- 27554008 TI - Corrigendum. PMID- 27554007 TI - Genetic testing of aetiology of intellectual disability in adults - the need for collaboration between paediatricians and adult physicians. PMID- 27554009 TI - Corrigendum. PMID- 27554010 TI - Corrigendum. PMID- 27554011 TI - Obituary: Kenneth A. R. Kennedy (1930-2014). PMID- 27554012 TI - Interfacial Screening in Ultrafast Voltammetry: A Theoretical Study of Redox Active Monolayers. AB - The impact of interfacial screening on electron transfer (ET) at ultrashort time scales is theoretically investigated on redox active monolayers by linear sweep voltammetry (LSV). The charging current associated with the nanosecond screening process is an important experimental determinant in finding both the reorganization energy (lambda) and electronic coupling (|M|) through ultrafast methods. On the one hand, time dependent decay of the charging current mitigates its impact on the current contribution from faradaic processes, while on the other hand, allowing substantial decay translates into a reduced upper-bound of applicable scan rates, which are crucial for ultrafast characterization. Analysis of the decay in the charging current suggests that the desired screening may be achieved for relatively weakly coupled systems within the charging time constant. For weakly coupled systems, the scan rate corresponding to nanoscale charging time constants appears to be suitable for the ultrafast investigation of ET characteristics. Moreover, the level of screening achieved at nanosecond decay times is shown to change with the coverage of electrode surface by monolayers; which appears to be accompanied by sharp drops in the time constant during successive saturation of interfacial layers by supporting ions (SI). These observations are expected to help design electrochemical device systems with interfaces capable of high faradaic efficiency at ultrafast limits. PMID- 27554014 TI - Two-week postpartum intrauterine contraception insertion: a study of feasibility, patient acceptability and short-term outcomes. AB - OBJECTIVE: To determine the feasibility and acceptability of inserting the levonorgestrel intrauterine system, LNG 52 mg IUS (LNG IUS), at 2 weeks postpartum. STUDY DESIGN: This prospective study of feasibility and patient acceptability recruited women interested in a postpartum LNG IUS and placed the LNG IUS under ultrasound guidance on days 14-20 postpartum. We determined feasibility by our ability to recruit and insert the LNG IUS in our predetermined sample size of 50 women. We measured our primary acceptability outcome at 6 months postpartum with the question: "Would you recommend Mirena placement at 2 weeks postpartum to a friend?" Other outcomes included expulsion and pain. The three study visits consisted of (1) insertion visit (14-20 days postpartum), (2) standard postpartum visit with a string check (6 weeks postpartum) and (3) research visit with sonography and assessment of the primary outcome (6 months postpartum). RESULTS: We enrolled 50 women over 8 months, all of whom received LNG IUS. Forty-three of the 50 (86%) provided follow-up data for the primary outcome. Of those, 93% (40/43) would recommend 2-week LNG IUS insertion to a friend, and 86% (37/43) continued using their LNG IUS at the conclusion of the 6 month visit. There were two partial expulsions; one was symptomatic. There were no uterine perforations. CONCLUSIONS: LNG IUS inserted at 2 weeks postpartum is feasible and acceptable to patients. These results offer evidence to support intrauterine contraception insertion prior to the onset of ovulation and at a potentially more convenient time point in the postpartum period. IMPLICATIONS: This study supports offering the LNG IUS beginning on the 14th postpartum day. The 4% expulsion rate is consistent with the rate of interval insertion and lower than immediate postplacental insertion. Additional research is needed to ensure a low risk of adverse events with other brands of intrauterine contraception. PMID- 27554013 TI - Ribosomal 18S rRNA base pairs with mRNA during eukaryotic translation initiation. AB - Eukaryotic mRNAs often contain a Kozak sequence that helps tether the ribosome to the AUG start codon. The mRNA of histone H4 (h4) does not undergo classical ribosome scanning but has evolved a specific tethering mechanism. The cryo-EM structure of the rabbit ribosome complex with mouse h4 shows that the mRNA forms a folded, repressive structure at the mRNA entry site on the 40S subunit next to the tip of helix 16 of 18S ribosomal RNA (rRNA). Toe-printing and mutational assays reveal that an interaction exists between a purine-rich sequence in h4 mRNA and a complementary UUUC sequence of helix h16. Together the present data establish that the h4 mRNA harbours a sequence complementary to an 18S rRNA sequence which tethers the mRNA to the ribosome to promote proper start codon positioning, complementing the interactions of the 40S subunit with the Kozak sequence that flanks the AUG start codon. PMID- 27554015 TI - The variable clinicopathological categories and role of human papillomavirus in cervical adenocarcinoma: A hospital based nation-wide multi-center retrospective study across China. AB - We investigated HPV in adenocarcinoma presenting and managed as cervical adenocarcinoma (CADC) at seven major representative regional cancer centres across China. From 1,051 CADC cases diagnosed locally in 2005-2010, 881 had available paraffin embedded tissue. Initial review excluded 154 cases as other diagnoses or inappropriate specimens. In 718 eligible cases consensus panel pathology diagnosis was made using an algorithm incorporating p16 and progesterone receptor immunohistochemistry (IHC). Classification of cervical adenocarcinoma categories was subject to substantial pathological disagreement. High-risk human papillomaviruses (HR-HPV) DNA was studied by the sensitive SPF10 PCR-DEIA-LiPA25 version 1 for L1 genes and type-specific HR-HPV E6/7 gene PCR's. HR-HPV prevalence in whole tissue samples in eligible tested CADC was 74.5%: 100.0% in neuro-endocrine carcinoma (NEC), 82.2% in classical cervical adenocarcinoma (ADC-CX), 40.0% in adenocarcinoma-not otherwise specified (ADC NOS) and 33.3% in endometrioid adenocarcinoma (ADC-ENDO). Higher mean age at diagnosis correlated with histological categories showing low HPV prevalence (Linear regression: beta= -13.794, p < 0.001). HPV-16 and 18 were associated with early development of CADC and a lower mean age correlated with carcinogenic risk of associated HPV (beta = -0.1829, p < 0.001). HPV-16 or HPV-18 was found in 88.2% of all HPV positive cases including multiple-infections. HPV-18 was the commonest HPV type in NEC (58.3%), ASC (40.2%) and ADC-CX (40.9%). The proportion of HPV-unrelated CADC and in different final histological categories varied geographically and by age. Although HPV negativity was predominantly associated with special categories of CADC, some HPV-negative usual adenocarcinomas indistinguishable by adjudicated microscopic diagnosis from ADC-CX were found and varied in frequency across China. PMID- 27554016 TI - Electrical stimulation enhances the acetylcholine receptors available for neuromuscular junction formation. AB - : Neuromuscular junctions (NMJ) are specialized synapses that link motor neurons with muscle fibers. These sites are fundamental to human muscle activity, controlling swallowing and breathing amongst many other vital functions. Study of this synapse formation is an essential area in neuroscience; the understanding of how neurons interact and control their targets during development and regeneration are fundamental questions. Existing data reveals that during initial stages of development neurons target and form synapses driven by biophysical and biochemical cues, and during later stages they require electrical activity to develop their functional interactions. The aim of this study was to investigate the effect of exogenous electrical stimulation (ES) electrodes directly in contact with cells, on the number and size of acetylcholine receptor (AChR) clusters available for NMJ formation. We used a novel in vitro model that utilizes a flexible electrical stimulation system and allows the systematic testing of several stimulation parameters simultaneously as well as the use of alternative electrode materials such as conductive polymers to deliver the stimulation. Functionality of NMJs under our co-culture conditions was demonstrated by monitoring changes in the responses of primary myoblasts to chemical stimulants that specifically target neuronal signaling. Our results suggest that biphasic electrical stimulation at 250Hz, 100MUs pulse width and current density of 1mA/cm2 for 8h, applied via either gold-coated mylar or the conductive polymer PPy, significantly increased the number and size of AChRs clusters available for NMJ formation. This study supports the beneficial use of direct electrical stimulation as a strategic therapy for neuromuscular disorders. STATEMENT OF SIGNIFICANCE: The beneficial effects of electrical stimulation (ES) on human cells in vitro and in vivo have long been known. Although the effects of stimulation are clear and the therapeutic benefits are known, no uniform parameters exist with regard to the duration, frequency and amplitude of the ES. To this end, we are answering several important questions on the parameters for ES of nerve and muscle monocultures and co-cultures by probing the effects on the enhancement of acetylcholine receptors (AChR) clustering available for neuromuscular junction formation using a conductive platform. This work opens the possibility to combine electrical stimulus delivered via conductive polymer substrates, from which biomolecules could also be delivered, providing opportunities to further enhance the therapeutic effect. PMID- 27554017 TI - Inter-trabecular angle: A parameter of trabecular bone architecture in the human proximal femur that reveals underlying topological motifs. AB - Trabecular bone is an intricate 3D network of struts and plates. Although the structure-function relations in trabecular bone have been studied since the time of Julius Wolff, controversy still exists regarding the architectural parameters responsible for its stability and resilience. We present a parameter that measures the angle between two connected trabeculae - the Inter-Trabecular Angle (ITA). We studied the ITA values derived from MUCT scans of different regions of the proximal femora of 5 individuals of different age and sex. We show that the ITA angle distribution of nodes with 3 connecting trabeculae has a mean close to 120 degrees , nodes with 4 connecting trabeculae has a mean close to 109 degrees and nodes of higher connectivity have mean ITA values around 100 degrees . This tendency to spread the ITAs around geometrically symmetrical motifs is highly conserved. The implication is that the ITAs are optimized such that the smallest amount of material spans the maximal 3D volume, and possibly by so doing trabecular bone might be better adapted to multidirectional loading. We also draw a parallel between trabecular bone and tensegrity structures - where lightweight, resilient and stable tetrahedron-based shapes contribute to strain redistribution amongst all the elements and to collective impact dampening. STATEMENT OF SIGNIFICANCE: The Inter-Trabecular Angle (ITA) is a new topological parameter of trabecular bone. The ITA characterizes the way trabeculae connect with each other at nodes, regardless of their thickness and shape. The mean ITA value of nodes with 3 trabeculae is close to 120 degrees , of nodes with 4 trabeculae is just below 109 degrees , and the mean ITA of nodes with 5 and more trabeculae is around 100 degrees . Thus the connections of trabeculae trend towards adopting symmetrical shapes. This implies that trabeculae can maximally span 3D space using the minimal amount of material. We draw a parallel between this motif and the concept of tensegrity - an engineering premise to which many living creatures conform at multiple levels of organization. PMID- 27554018 TI - Reinforcement of poly-l-lactic acid electrospun membranes with strontium borosilicate bioactive glasses for bone tissue engineering. AB - Herein, for the first time, we combined poly-l-lactic acid (PLLA) with a strontium borosilicate bioactive glass (BBG-Sr) using electrospinning to fabricate a composite bioactive PLLA membrane loaded with 10% (w/w) of BBG-Sr glass particles (PLLA-BBG-Sr). The composites were characterised by scanning electron microscopy (SEM) and microcomputer tomography (MU-CT), and the results showed that we successfully fabricated smooth and uniform fibres (1-3MUm in width) with a homogeneous distribution of BBG-Sr microparticles (<45MUm). Degradation studies (in phosphate buffered saline) demonstrated that the incorporation of BBG-Sr glass particles into the PLLA membranes increased their degradability and water uptake with a continuous release of cations. The addition of BBG-Sr glass particles enhanced the membrane's mechanical properties (69% higher Young modulus and 36% higher tensile strength). Furthermore, cellular in vitro evaluation using bone marrow-derived mesenchymal stem cells (BM-MSCs) demonstrated that PLLA-BBG-Sr membranes promoted the osteogenic differentiation of the cells as demonstrated by increased alkaline phosphatase activity and up regulated osteogenic gene expression (Alpl, Sp7 and Bglap) in relation to PLLA alone. These results strongly suggest that the composite PLLA membranes reinforced with the BBG-Sr glass particles have potential as an effective biomaterial capable of promoting bone regeneration. STATEMENT OF SIGNIFICANCE: PLLA membranes were reinforced with 10% (w/w) of strontium-bioactive borosilicate glass microparticles, and their capacity to induce the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) was evaluated. These membranes presented an increased: degradability, water uptake, Young modulus and tensile strength. We also demonstrated that these membranes are non-cytotoxic and promote the attachment of BM-MSCs. The addition of the glass microparticles into the PLLA membranes promoted the increase of ALP activity (under osteogenic conditions), as well as the BM-MSCs osteogenic differentiation as shown by the upregulation of Alpl, Sp7 and Bglap gene expression. Overall, we demonstrated that the reinforcement of PLLA with glass microparticles results in a biomaterial with the appropriate properties for the regeneration of bone tissue. PMID- 27554019 TI - Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo. AB - Similar to calcium phosphates, magnesium phosphate (MgP) ceramics have been shown to be biocompatible and support favorable conditions for bone cells. Micropores below 25MUm (MgP25), between 25 and 53MUm (MgP53), or no micropores (MgP0) were introduced into MgP scaffolds using different sizes of an NaCl template. The porosities of MgP25 and MgP53 were found to be higher than that of MgP0 because of their micro-sized pores. Both in vitro and in vivo analysis showed that MgP scaffolds with high porosity promoted rapid biodegradation. Implantation of the MgP0, MgP25, and MgP53 scaffolds into rabbit calvarial defects (with 4- and 6-mm diameters) was assessed at two times points (4 and 8weeks), followed by analysis of bone regeneration. The micro-CT and histologic analyses of the 4-mm defect showed that the MgP25 and MgP53 scaffolds were degraded completely at 4weeks with simultaneous bone and marrow-like structure regeneration. For the 6-mm defect, a similar pattern of regeneration was observed. These results indicate that the rate of degradation is associated with bone regeneration. The MgP25 and MgP53 scaffold-implanted bone showed a better lamellar structure and enhanced calcification compared to the MgP0 scaffold because of their porosity and degradation rate. Tartrate-resistant acid phosphatase (TRAP) staining indicated that the newly formed bone was undergoing maturation and remodeling. Overall, these data suggest that the pore architecture of MgP ceramic scaffolds greatly influence bone formation and remodeling activities and thus should be considered in the design of new scaffolds for long-term bone tissue regeneration. STATEMENT OF SIGNIFICANCE: The pore structural conditions of scaffold, including porosity, pore size, pore morphology, and pore interconnectivity affect cell ingrowth, mechanical properties and biodegradabilities, which are key components of scaffold in bone tissue regeneration. In this study, we designed hierarchical pore structure of the magnesium phosphate (MgP) scaffold by combination of the 3D printing process, self-setting reaction and salt-leaching technique, and first studied the effect of pore structures of bioceramic scaffolds on bone tissue regeneration through both in vitro and in vivo studies (rabbit calvarial model). The MgP scaffolds with higher porosity promoted more rapid biodegradation and enhanced new bone formation and remodeling activities at the same time. PMID- 27554020 TI - Design of an elasticized collagen scaffold: A method to induce elasticity in a rigid protein. AB - Type I collagen is widely applied as a biomaterial for tissue regeneration. In the extracellular matrix, collagen provides strength but not elasticity under large deformations, a characteristic crucial for dynamic organs and generally imparted by elastic fibers. In this study, a methodology is described to induce elastic-like characteristics in a scaffold consisting of solely type I collagen. Tubular scaffolds are prepared from collagen fibrils by a casting, molding, freezing and lyophilization process. The lyophilized constructs are compressed, corrugated and subsequently chemically crosslinked with carbodiimide in the corrugated position. This procedure induces elastic-like properties in the scaffolds that could be repeatedly stretched five times their original length for at least 1000 cycles. The induced elasticity is entropy driven and can be explained by the introduction of hydrophobic patches that are disrupted upon stretching thus increasing the hydrophobic-hydrophilic interface. The scaffolds are cytocompatible as demonstrated by fibroblast cell culture. In conclusion, a new straightforward technique is described to endow unique elastic characteristics to scaffolds prepared from type I collagen alone. Scaffolds may be useful for engineering of dynamic tissues such as blood vessels, ligaments, and lung. STATEMENT OF SIGNIFICANCE: In this research report, a methodology is presented to introduce elasticity to biomaterials consisting of only type I collagen fibrils. The method comprises physical compression and corrugation in combination with chemical crosslinking. By introducing elasticity to collagen biomaterials, their application in regenerative medicine may be expanded to dynamic organs such as blood vessels, ligaments and lung. The combination of strength and elasticity in one single natural biomaterial may also "simplify" the design of new scaffolds. PMID- 27554021 TI - Probing multi-scale mechanical damage in connective tissues using X-ray diffraction. AB - : The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. STATEMENT OF SIGNIFICANCE: This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. PMID- 27554022 TI - Liquid chromatography quadrupole linear ion trap mass spectrometry for quantitative steroid hormone analysis in plasma, urine, saliva and hair. AB - Steroid analysis is being conquered by liquid chromatography tandem mass spectrometry (LC-MS/MS) benefiting from higher standardization, selectivity and diversity. Regarding high throughput in routine diagnostics rapid chromatography is mandatory. Introducing MS(3) (MS/MS/MS), specificity of mass spectrometric detection can be enhanced without sacrificing analysis time. 100mL of human plasma/serum, saliva, urine and 10-20mg of hair are used for the simultaneous quantification of 17alpha-hydroxyprogesterone, aldosterone, androstenedione, cortisol, cortisone, dehydroepiandrosterone sulfate (DHEAS), estradiol, progesterone, and testosterone using online solid phase extraction (SPE) LC-MS/MS or LC-MS(3). Steroids can be analyzed in 4min after a single manual dilution and protein precipitation step. In complex sample matrices like hair MS(3) detection was found to be appropriate for quantitation. Lower limits of quantitation ranged from 37pmol/L (estradiol) up to 3.1nmol/L (DHEAS). General accuracy was 89-107% with between-run imprecision <=10%. Comparison to immunoassays revealed significant differences in quantitation for urinary cortisol (-71% mean), aldosterone (-40% mean) and plasma aldosterone (-45% mean). The comparison of MS(2) and MS(3) quantitation of hair cortisol also revealed significant differences. In general, quantitation via MS(3) was not applicable for a long time. But with the current generation of mass spectrometers quantitation via MS(3) can be superior to MS(2) regarding specificity and accuracy when dealing with matrix issues. However, drawbacks regarding flexibility and precision have to be taken into account. Concludingly, simple protein precipitation combined with rapid online SPE LC-MS/MS/MS allows us to quantify over broad, essential concentration ranges in human serum, saliva, urine and hair. PMID- 27554023 TI - Characterization of methacrylate chromatographic monoliths bearing affinity ligands. AB - We investigated effect of immobilization procedure and monolith structure on chromatographic performance of methacrylate monoliths bearing affinity ligands. Monoliths of different pore size and various affinity ligands were prepared and characterized using physical and chromatographic methods. When testing protein A monoliths with different protein A ligand densities, a significant nonlinear effect of ligand density on dynamic binding capacity (DBC) for IgG was obtained and accurately described by Langmuir isotherm curve enabling estimation of protein A utilization as a function of ligand density. Maximal IgG binding capacity was found to be at least 12mg/mL exceeding theoretical monolayer adsorption value of 7.8mg/mL assuming hexagonal packing and IgG hydrodynamic diameter of 11nm. Observed discrepancy was explained by shrinkage of IgG during adsorption on protein A experimentally determined through calculated adsorbed IgG layer thickness of 5.4nm from pressure drop data. For monoliths with different pore size maximal immobilized densities of protein A as well as IgG dynamic capacity linearly correlates with monolith surface area indicating constant ligand utilization. Finally, IgGs toward different plasma proteins were immobilized via the hydrazide coupling chemistry to provide oriented immobilization. DBC was found to be flow independent and was increasing with the size of bound protein. Despite DBC was lower than IgG capacity to immobilized protein A, ligand utilization was higher. PMID- 27554024 TI - Thermodynamic modeling of protein retention in mixed-mode chromatography: An extended model for isocratic and dual gradient elution chromatography. AB - An extended model is developed to describe protein retention in mixed-mode chromatography based on thermodynamic principles. Special features are the incorporation of pH dependence of the ionic interaction on a mixed-mode resin and the addition of a water term into the model which enables one to describe the total number of water molecules released at the hydrophobic interfaces upon protein-ligand binding. Examples are presented on how to determine the model parameters using isocratic elution chromatography. Four mixed-mode anion exchanger prototype resins with different surface chemistries and ligand densities were tested using isocratic elution of two monoclonal antibodies at different pH values (7-10) and encompassed a wide range of NaCl concentrations (0 5M). U-shape mixed-mode retention curves were observed for all four resins. By taking into account of the deprotonation and protonation of the weak cationic functional groups in these mixed-mode anion-exchanger prototype resins, conditions which favor protein-ligand binding via mixed-mode strong cationic ligands as well as conditions which favor protein-ligand binding via both mixed mode strong cationic ligands and non-hydrophobic weak cationic ligands were identified. The changes in the retention curves with pH, salt, protein, and ligand can be described very well by the extended model using meaningful thermodynamic parameters like Gibbs energy, number of ionic and hydrophobic interactions, total number of released water molecules as well as modulator interaction constant. Furthermore, the fitted model parameters based on isocratic elution data can also be used to predict protein retention in dual salt-pH gradient elution chromatography. PMID- 27554025 TI - A micellar electrokinetic chromatography-mass spectrometry approach using in capillary diastereomeric derivatization for fully automatized chiral analysis of amino acids. AB - In the context of bioanalytical method development, process automatization is nowadays a necessity in order to save time, improve method reliability and reduce costs. For the first time, a fully automatized micellar electrokinetic chromatography-mass spectrometry (MEKC-MS) method with in-capillary derivatization was developed for the chiral analysis of d- and l-amino acids using (-)-1-(9-fluorenyl) ethyl chloroformate (FLEC) as labeling reagent. The derivatization procedure was optimized using an experimental design approach leading to the following conditions: sample and FLEC plugs in a 2:1 ratio (15s, 30mbar: 7.5s, 30mbar) followed by 15min of mixing using a voltage of 0.1kV. The formed diastereomers were then separated using a background electrolyte (BGE) consisting of 150mM ammonium perfluorooctanoate (APFO) (pH=9.5) and detected by mass spectrometry (MS). Complete chiral resolution was obtained for 8 amino acids, while partial separation was achieved for 6 other amino acid pairs. The method showed good reproducibility and linearity in the low micromolar concentration range. The applicability of the method to biological samples was tested by analyzing artificial cerebrospinal fluid (aCSF) samples. PMID- 27554026 TI - Alternative solvents for improving the greenness of normal phase liquid chromatography of lipid classes. AB - An evaluation of solvents alternative to n-heptane (d-limonene and hexamethyldisiloxane) and chloroform (cyclopentyl methyl ether, 2 methyltetrahydrofuran and isopentyl acetate) was developed for lipid classes separation of non-polar cholesteryl ester to highly polar phospholipids by high performance liquid chromatography on bare silica stationary phase and evaporative light-scattering detection. Screening of alternative solvents was used to estimate their compatibility with liquid chromatography and evaporative light scattering detection and to evaluate their chromatographic selectivity. This work shows that n-heptane can be advantageously replaced by hexamethyldisiloxane. An increase of non-polar lipids retention is observed with hexamethyldisiloxane as weak solvent. Chloroform, which is largely used for lipid analysis, might be replaced efficaciously by cyclopentyl methyl ether, 2-methyltetrahydrofuran or isopentyl acetate. Aside from offering a different selectivity, the gradients composed by one or both alternative solvents gave efficient and comparable or even better separations than those obtained with conventional solvents. PMID- 27554027 TI - Advances in ultra-high performance liquid chromatography coupled to tandem mass spectrometry for sensitive detection of several food allergens in complex and processed foodstuffs. AB - Sensitive detection of food allergens is affected by food processing and foodstuff complexity. It is therefore a challenge to detect cross-contamination in food production that could endanger an allergic customer's life. Here we used ultra-high performance liquid chromatography coupled to tandem mass spectrometry for simultaneous detection of traces of milk (casein, whey protein), egg (yolk, white), soybean, and peanut allergens in different complex and/or heat-processed foodstuffs. The method is based on a single protocol (extraction, trypsin digestion, and purification) applicable to the different tested foodstuffs: chocolate, ice cream, tomato sauce, and processed cookies. The determined limits of quantitation, expressed in total milk, egg, peanut, or soy proteins (and not soluble proteins) per kilogram of food, are: 0.5mg/kg for milk (detection of caseins), 5mg/kg for milk (detection of whey), 2.5mg/kg for peanut, 5mg/kg for soy, 3.4mg/kg for egg (detection of egg white), and 30.8mg/kg for egg (detection of egg yolk). The main advantage is the ability of the method to detect four major food allergens simultaneously in processed and complex matrices with very high sensitivity and specificity. PMID- 27554028 TI - Online-storage recycling counter-current chromatography for preparative isolation of naphthaquinones from Arnebia euchroma (Royle) Johnst. AB - Counter-current Chromatography (CCC) has gradually become a popular method for preparative separation, especially in natural product isolation. As an effective separation method, one-dimensional (1D) CCC often results in insufficiently resolved peaks, due to limitations in the separation efficiency and peak capacity in an equipment. Therefore, two dimensional (2D)/multi-dimensional (multi-D) CCC strategies with recycling elution mode were developed to achieve successful separation of target compounds. However, the reported 2D or multi-D CCC approaches lead to experimental costs, complicated procedures, higher requirements for equipment, and increased time consumption. In this study, an online-storage recycling (OSR) CCC strategy was designed to achieve sequential recycling elution for multi-fractions of effluent in non-stop separation with single instrument using three 6-port valves and two storage loops, which would be realized by introducing 2D or multi-D CCC method before. In this non-stop separation system, the fraction C of effluent was subjected to recycling separation while the other fractions (A and B) were storing online, following which these two fractions were subjected to subsequent recycling separations in order, after the completion of the previous recycling elution. Then, six natural occurring naphthaquinone analogues, namely, shikonin (1), propionylshikonin (2), deoxyshikonin (3), isobutyrylshikonin (4), beta, beta-dimethylacrylshikonin (5) and isovalerylshikonin (6), were isolated from the crude extract of Arnebia euchroma in single run. The purities of all compounds were > 95.0% as determined by HPLC, and their structures were determined by means of UV, MS, (1)H NMR, (13)C NMR, and optical rotatory dispersion (ORD). PMID- 27554029 TI - Accurate determination of fiber water-retaining capability at process conditions by headspace gas chromatography. AB - This work reports on a method for the accurate determination of fiber water retaining capability at process conditions by headspace gas chromatography (HS GC) method. The method was based the HS-GC measurement of water vapor on a set closed vials containing in a given amount pulp with different amounts of water addition, from under-saturation to over-saturation. By plotting the equilibrated water vapor signal vs. the amount of water added in pulp, two different trend lines can be observed, in which the transition of the lines corresponds to fiber water-retaining capability. The results showed that the HS-GC method has good measurement precision (much better than the reference method) and good accuracy. The present method can be also used for determining pulp fiber water-retaining capability at the process temperatures in both laboratory research and mill applications. PMID- 27554030 TI - In-line coupling of an achiral-chiral column to investigate the enantioselective in vitro metabolism of the pesticide Fenamiphos by human liver microsomes. AB - The distinct activity and toxicity of enantiomers has increased concern about the use of chiral pesticides. The chiral pesticide Fenamiphos (FS) is employed as a racemic mixture to control nematode pests. Although recent studies revealed that FS enantiomers possess different toxicity, the toxicokinetics and liver metabolism of these enantiomers in humans remain unclear. This study characterizes the in vitro metabolism of rac-FS, (+)-FS, and (-)-FS by human liver microsomes and predicts some toxicokinetic parameters. First, a new enantioselective HPLC method was developed to analyze FS and its metabolites [fenamiphos sulfoxide (FSO) and fenamiphos sulfone (FSO2)]. Chiral separation of the stereoisomers was accomplished in an in-line coupled achiral-chiral column (Lichrosorb Si60 - Chiralpak AS-H); hexane: ethanol: methanol (85:12:3, v/v/v) was used as mobile phase at a flow rate of 1.2mLmin-1. Then, the HPLC method was fully validated. All the evaluated parameters agreed with the European Medicines Agency guideline. Finally, the enantioselective kinetic parameters were determined for CYP450 enzymes. The predicted toxicokinetic parameters showed that the liver exclusively eliminated FS without stereoselectivity. PMID- 27554031 TI - Rituximab versus fingolimod after natalizumab in multiple sclerosis: Also consider progressive multifocal leukoencephalopathy risk. PMID- 27554032 TI - Materials technology in drug eluting balloons: Current and future perspectives. AB - The coating material technology is important for the delivery of anti proliferative drugs from the surface of drug-eluting balloons (DEBs), which are emerging as alternatives to drug-eluting stents (DES) in the field of interventional cardiology. Currently, several shortcomings limit their competition with DES, including low drug transfer efficiency to the arterial tissues and undesirable particulate generation from the coating matrix. In this review, we provide a survey of the materials used in existing DEBs, and discussed the mechanisms of actions of both the drugs and coating materials. The type of drug and the influence of the coating material characteristics on the drug uptake, distribution and retention in arterial tissues are described. We also summarize the novel coating excipients under development and provide our perspective on the possible use of nano-scale carriers to address the shortcomings of current coating technology. The scope of this review includes only materials that have been approved for biomedical applications or are generally recognized as safe (GRAS) for drug delivery. PMID- 27554034 TI - Treatment Patterns and Visual Outcomes during the Maintenance Phase of Treat-and Extend Therapy for Age-Related Macular Degeneration. AB - PURPOSE: To present the treatment patterns, disease activity, and visual outcomes of eyes in the maintenance phase of a treat-and-extend regimen for neovascular age-related macular degeneration (nAMD). To compare the maintenance phase behavior of eyes with a shorter induction phase (<=3 injections) with those requiring a longer induction phase (>3 injections). DESIGN: Database observational study. PARTICIPANTS: Eyes with nAMD receiving anti-vascular endothelial growth factor (VEGF) treatment using a treat-and-extend protocol. Persistently active eyes were excluded, as were eyes with <12 months follow-up during the maintenance phase. METHODS: Clinical information from a large prospective international voluntary registry of nAMD was analyzed. The maintenance phase was defined as starting at the first clinician-reported grading of lesion inactivity. MAIN OUTCOME MEASURES: For analyses by eye: treatment interval at first reactivation; time to first reactivation; and visual acuity change during the study period. For analyses by visit: choroidal neovascular membrane activity graded by the treating physician; time since previous injection; and visual acuity loss since previous injection (>0 letters and >=15 letters). RESULTS: The mean change in visual acuity during the maintenance phase was +1.0 letters at 12 months -0.6 letters at 24 months and -1.5 at 36 months. Median treatment interval increased from 35 days at study entry to 63 days at 12 months and was 60 days at 36 months. 38.5% of eyes remained inactive at all observed visits during the maintenance phase (minimum 1 year follow-up, mean 945 days). The most common treatment interval at first reactivation was 8 weeks. Treatment intervals beyond 12 weeks seemed to be associated with increased risk of disease reactivation, with risk of reactivation reaching 37.4% at treatment intervals of >=20 weeks. Eyes with a longer induction phase had worse visual outcomes in the maintenance phase, and earlier and more-frequent disease reactivation, although they received injections less frequently. CONCLUSIONS: The detailed behavior of eyes in the maintenance phase of treat-and-extend management for nAMD is presented. Visual acuity was well maintained during the study period. The most common interval at which reactivation first occurred was 8 weeks. Longer duration of induction phase was associated with worse visual acuity outcomes and earlier disease reactivation, perhaps because of undertreatment. PMID- 27554035 TI - Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study. AB - PURPOSE: Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. DESIGN: Prospective cohort study. PARTICIPANTS: Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. METHODS: By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. MAIN OUTCOME MEASURES: During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; >= or <22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated. RESULTS: Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06-1.97); in particular, a report within the past 2 years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07 3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity >=0.36), although associations were strongest in relation to the POAG subtypes with IOP <22 mmHg (MVRR, 1.93; 95% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95% CI, 1.32-3.88). CONCLUSIONS: Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies. PMID- 27554036 TI - Association between Intraocular Pressure and Rates of Retinal Nerve Fiber Layer Loss Measured by Optical Coherence Tomography. AB - PURPOSE: To evaluate the relationship between intraocular pressure (IOP) and rates of retinal nerve fiber layer (RNFL) thickness change over time measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Observational cohort study. PARTICIPANTS: The study involved 547 eyes of 339 patients followed up for an average of 3.9+/-0.9 years. Three hundred eight (56.3%) had a diagnosis of glaucoma and 239 (43.7%) were considered glaucoma suspects. METHODS: All eyes underwent imaging using the Spectralis SD OCT (Heidelberg Engineering GmbH, Heidelberg, Germany), along with IOP measurements and standard automated perimetry (SAP). Glaucoma progression was defined as a result of "Likely Progression" from the Guided Progression Analysis software for SAP. Linear mixed models were used to investigate the relationship between average IOP during follow-up and rates of RNFL thickness change, while taking into account potential confounding factors such as age, race, corneal thickness, and baseline disease severity. MAIN OUTCOME MEASURES: The association between IOP and rates of global and sectorial RNFL thickness loss measured by SD OCT. RESULTS: Forty-six eyes (8.4%) showed progression on SAP during follow-up. Rates of global RNFL thickness change in eyes that progressed by SAP were faster than in those that did not progress (-1.02 vs. -0.61 MUm/year, respectively; P = 0.002). For progressing eyes, each 1-mmHg higher average in IOP during follow-up was associated with an additional average loss of 0.20 MUm/year (95% confidence interval [CI]: 0.08 to 0.31 MUm/year; P < 0.001) of global RNFL thickness versus only 0.04 MUm/year (95% CI: 0.01 to 0.07 MUm/year; P = 0.015) for nonprogressing eyes. The largest associations between IOP and rates of RNFL change were seen for measurements from the temporal superior and temporal inferior sectors, whereas the smallest association was seen for measurements from the nasal sector. CONCLUSIONS: Higher levels of IOP during follow-up were associated with faster rates of RNFL loss over time measured by SD OCT. These findings support the use of SD OCT RNFL thickness measurements as biomarkers for the evaluation of the efficacy of IOP lowering therapies to slow down the rate of disease progression. PMID- 27554038 TI - Autonomy, consent and responsibility. Part II. Informed consent in medical care and in the law. AB - Legal recognition of patient's rights aspired to change clinical relationship and medical lex artis. However, its implementation has been hampered by the scarcity of resources and the abundance of regulations. For several years, autonomy, consent, and responsibility have formed one of the backbones of the medical profession. However, they have sparked controversy and professional discomfort. In the first part of this article, we examine the conceptual and regulatory limitations of the principle of autonomy as the basis of informed consent. We approach the subject from philosophical, historical, legal, bioethical, deontological, and professional standpoints. In the second part, we cover the viability of informed consent in health care and its relationship with legal responsibility. PMID- 27554037 TI - An ultrasensitive electrogenerated chemiluminescence-based immunoassay for specific detection of Zika virus. AB - Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs can capture as little as 1 PFU of ZIKV in 100 MUl of saline, human plasma, or human urine. This platform has the potential for development as a cost-effective, rapid and ultrasensitive assay for the detection of ZIKV and possibly other viruses in clinical diagnosis, epidemiologic and vector surveillance, and laboratory research. PMID- 27554039 TI - Serie: pulmonary thromboembolism: current controversies. PMID- 27554041 TI - miR-297 acts as an oncogene by targeting GPC5 in lung adenocarcinoma. AB - OBJECTIVES: Emerging studies have demonstrated that microRNAs (miRNAs) play crucial roles in carcinogenesis of many developing human tumours. However, the functions and mechanisms of miR-297 in lung cancer have, up to now, been largely undefined. MATERIALS AND METHODS: Here, miR-297 expression was measured in lung adenocarcinoma tissues and cell lines, using qRT-PCR. Lung adenocarcinoma cell line was treated with an miR-297 mimic. MTT and colony analysis were performed to detect cell proliferation and colony formation. The direct target gene of miR-297 was assessed by qRT-PCR, Western blotting and luciferase assays. RESULTS: We demonstrated that miR-297 expression was upregulated in lung adenocarcinomas compared to adjacent normal tissues. Expression of miR-297 was also upregulated in tested lung adenocarcinoma cell lines. Ectopic expression of miR-297 enhanced lung adenocarcinoma cell proliferation and colony formation. Furthermore, overexpression of miR-297 promoted cell migration and invasion. In addition, we identified Glypican-5 (GPC5) as a direct target gene of miR-297 in lung adenocarcinoma cells. Expression of GPC5 was downregulated in both lung adenocarcinoma tissues and cell lines. Moreover, expression of GPC5 was inversely associated with expression of miR-297 in lung adenocarcinoma tissues. CONCLUSIONS: These results suggest that miR-297 acted as an oncogenic miRNA, partly by targeting GPC5, adenocarcinoma of the lung. PMID- 27554040 TI - Aberrant expression of miR-153 is associated with overexpression of hypoxia inducible factor-1alpha in refractory epilepsy. AB - Evidence suggest that overexpression of hypoxia-inducible factor-1alpha (HIF 1alpha) is linked to multidrug resistance of epilepsy. Here we explored whether aberrant expression of HIF-1alpha is regulated by miRNAs. Genome-wide microRNA expression profiling was performed on temporal cortex resected from mesial temporal lobe epilepsy (mTLE) patients and age-matched controls. miRNAs that are putative regulator of HIF-1alpha were predicted via target scan and confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Mimics or miRNA morpholino inhibitors were transfected in astrocytes and luciferase reporter assay was applied to detect HIF-11alpha expression. Microarray profiling identified down-regulated miR-153 as a putative regulator of HIF-1alpha in temporal cortex resected from surgical mTLE patients. RT-qPCR confirmed down regulation of miR-153 in plasma of mTLE patients in an independent validation cohort. Knockdown of miR-153 significantly enhanced expression of HIF-1alpha while forced expression of miR-153 dramatically inhibited HIF-1alpha expression in pharmacoresistant astrocyte model. Luciferase assay established that miR-153 might inhibit HIF-1alpha expression via directly targeting two binding sites in the 3'UTR region of HIF-1alpha transcript. These data suggest that down regulation of miR-153 may contribute to enhanced expression of HIF-1alpha in mTLE and serve as a novel biomarker and treatment target for epilepsy. PMID- 27554042 TI - Toxicology and Applied Pharmacology (TAAP): Building on the past for the new science of the twenty-first century. PMID- 27554043 TI - Destabilization of mitochondrial functions as a target against breast cancer progression: Role of TPP(+)-linked-polyhydroxybenzoates. AB - Mitochondrion is an accepted molecular target in cancer treatment since it exhibits a higher transmembrane potential in cancer cells, making it susceptible to be targeted by lipophilic-delocalized cations of triphenylphosphonium (TPP(+)). Thus, we evaluated five TPP(+)-linked decyl polyhydroxybenzoates as potential cytotoxic agents in several human breast cancer cell lines that differ in estrogen receptor and HER2/neu expression, and in metabolic profile. Results showed that all cell lines tested were sensitive to the cytotoxic action of these compounds. The mechanism underlying the cytotoxicity would be triggered by their weak uncoupling effect on the oxidative phosphorylation system, while having a wider and safer therapeutic range than other uncouplers and a significant lowering in transmembrane potential. Noteworthy, while the TPP(+)-derivatives alone led to almost negligible losses of ATP, when these were added in the presence of an AMP-activated protein kinase inhibitor, the levels of ATP fell greatly. Overall, data presented suggest that decyl polyhydroxybenzoates-TPP(+) and its derivatives warrant future investigation as potential anti-tumor agents. PMID- 27554044 TI - Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression. AB - Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that beta-actin, an important component of cytoskeleton, has been significantly down regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of beta-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. PMID- 27554045 TI - PKC-alpha modulation by miR-483-3p in platinum-resistant ovarian carcinoma cells. AB - The occurrence of drug resistance limits the efficacy of platinum compounds in the cure of ovarian carcinoma. Since microRNAs (miRNAs) may contribute to this phenomenon by regulating different aspects of tumor cell response, the aim of this study was to exploit the analysis of expression of miRNAs in platinum sensitive/resistant cells in an attempt to identify potential regulators of drug response. MiR-483-3p, which may participate in apoptosis and cell proliferation regulation, was found up-regulated in 4 platinum resistant variants, particularly in the IGROV-1/Pt1 subline, versus parental cells. Transfection of a synthetic precursor of miR-483-3p in IGROV-1 parental cells elicited a marked up-regulation of the miRNA levels. Growth-inhibition and colony-forming assays indicated that miR-483-3p over-expression reduced cell growth and conferred mild levels of cisplatin resistance in IGROV-1 cells, by interference with their proliferative potential. Predicted targets of miR-483-3p included PRKCA (encoding PKC-alpha), previously reported to be associated to platinum-resistance in ovarian carcinoma. We found that miR-483-3p directly targeted PRKCA in IGROV-1 cells. In keeping with this finding, cisplatin sensitivity of IGROV-1 cells decreased upon molecular/pharmacological inhibition of PKC-alpha. Overall, our results suggest that overexpression of miR-483-3p by ovarian carcinoma platinum-resistant cells may interfere with their proliferation, thus protecting them from DNA damage induced by platinum compounds and ultimately representing a drug-resistance mechanism. The impairment of cell growth may account for low levels of drug resistance that could be relevant in the clinical setting. PMID- 27554046 TI - Action mechanisms of histone deacetylase inhibitors in the treatment of hematological malignancies. AB - Histone deacetylases (HDACs) critically regulate gene expression by determining the acetylation status of histones. Studies have increasingly focused on the activities of HDACs, especially involving non-histone proteins, and their various biological effects. Aberrant HDAC expression observed in several kinds of human tumors makes HDACs potential targets for cancer treatment. Several preclinical studies have suggested that HDAC inhibitors show some efficacy in the treatment of acute myelogenous leukemia with AML1-ETO, which mediates transcriptional repression through its interaction with a complex including HDAC1. Recurrent mutations in epigenetic regulators are found in T-cell lymphomas (TCLs), and HDAC inhibitors and hypomethylating agents were shown to act cooperatively in the treatment of TCLs. Preclinical modeling has suggested that persistent activation of the signal transducer and activator of transcription signaling pathway could serve as a useful biomarker of resistance to HDAC inhibitor in patients with cutaneous TCL. Panobinostat, a pan-HDAC inhibitor, in combination with bortezomib and dexamethasone, has achieved longer progression-free survival in patients with relapsed/refractory multiple myeloma (MM) than the placebo in combination with bortezomib and dexamethasone. Panobinostat inhibited MM cell growth by degrading protein phosphatase 3 catalytic subunit alpha (PPP3CA), a catalytic subunit of calcineurin. This degradation was suggested to be mediated by the blockade of the chaperone function of heat shock protein 90 due to HDAC6 inhibition. Aberrant PPP3CA expression in advanced MM indicated a possible correlation between high PPP3CA expression and the pathogenesis of MM. Furthermore, PPP3CA was suggested as a common target of panobinostat and bortezomib. PMID- 27554047 TI - Relationship between vitamin D level and left atrial fibrosis in patients with lone paroxysmal atrial fibrillation undergoing cryoballoon-based catheter ablation. AB - BACKGROUND: Left atrial (LA) fibrosis is known as the hallmark for arrhythmogenic substrate in atrial fibrillation (AF). Quantification of LA fibrosis by using delayed-enhanced magnetic resonance imaging (DE-MRI) in AF patients is a pioneering noninvasive technique. Vitamin D (vitD) negatively regulates the renin angiotensin system, binds to vitD receptors on cardiac myocytes, and has antioxidant properties that may ameliorate the inflammation and proarrhythmic substrate formation. However, its role in LA fibrosis is unclear. We aimed to investigate the association of serum 25(OH)D level with the extent of LA fibrosis by using DE-MRI and also predictors for AF recurrence after cryoablation was assessed in patients with paroxysmal AF. METHODS: A total of 48 patients with lone paroxysmal AF (41.7% female; age: 48.5+/-8.4 years) who underwent DE-MRI at 1.5T and initial cryoballoon-based catheter ablation along with 48 healthy control subjects were enrolled. Fibrosis degree was categorized according to Utah class defined in the DECAAF study. RESULTS: Serum 25(OH)D levels were significantly lower in AF group compared to control group (25.8+/-7.6ng/ml vs. 31.0+/-9.5ng/ml, p=0.004). Serum 25(OH)D levels were associated with moderate severe LA fibrosis independent of other measures (OR: 0.72, 95% CI: 0.54-0.97, p=0.028). At a mean 16.5+/-2.6 months follow-up, late recurrence was observed in 10 (20.8%) patients. In multivariable Cox regression analysis, LA volume index (HR: 1.42, 95% CI: 1.01-2.01, p=0.045) and the extent of LA fibrosis (HR: 1.14, 95% CI: 1.01-1.28, p=0.034) were found as independently associated with late AF recurrence during follow-up. CONCLUSION: Lower levels of serum 25(OH)D are significantly associated with more extensive LA fibrosis in patients with lone paroxysmal AF and may be implicated in the pathophysiology of AF recurrence after cryoablation. Further large-scale studies are needed to elucidate the exact role of vitD deficiency and replacement on LA fibrosis. PMID- 27554048 TI - Dual origin multiple plexus-like coronary to pulmonary artery fistulas - Consideration of their etiology and therapeutic strategy. AB - BACKGROUND: Multiple plexus-like coronary to pulmonary fistulas (CAPFs) originating from bilateral coronary arteries are a rare type of coronary artery fistula (CAF). Their etiology and therapeutic strategy are discussed. METHODS AND RESULTS: Three patients were diagnosed with dual origin plexus-like CAFs drained to the pulmonary artery trunk. Their ages ranged from 40 to 78 years. Enhanced computed tomography could clearly demonstrate three-dimensional anatomy of CAPFs. Four catheter interventions were performed in all 3 patients. Antegrade approach was applied in 2 procedures and retrograde approach in 2 procedures. A detachable coil was used in 3 procedures and a combination of a vascular plug and detachable coils for 1 procedure. The effective occlusion was achieved in all patients without complications. Follow-up myocardial scintigraphy showed no perfusion defect in all patients. CONCLUSIONS: CAPFs in our cases, which developed in their adulthood, anatomically correspond with the vasa vasorum of the proximal of the great arteries. The dual origin multiple plexus-like CAPFs might develop from the vasa vasorum of the proximal portion of the great arteries with age. The antegrade approach would be effective because even dual origin multiple plexus like CAFs converged and drained to a single major exit of the pulmonary trunk. Catheter occlusion could be feasible and safe for dual origin multiple plexus like CAPFs. PMID- 27554049 TI - Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy. AB - BACKGROUND: The prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear. METHODS: We measured plasma alpha-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness >=15mm). RESULTS: Two patients (1.1%) showed very low alpha-galactosidase A activity [0.0 and 0.3nmol/hr/ml (normal range: 3.6-17.6nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16mm and posterior wall thickness of 11mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified. CONCLUSIONS: The prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation. PMID- 27554050 TI - Association between elevated blood glucose level on admission and long-term mortality in patients with acute decompensated heart failure. AB - BACKGROUND: The effect of elevated blood glucose (BG) levels on the long-term prognosis of acute decompensated heart failure (ADHF) patients has not been well defined. The purpose of this study is to evaluate the long-term prognosis of ADHF with elevated BG. METHODS: A cohort of patients consecutively admitted to the cardiac intensive care unit from 2007 to 2011 was studied. Among these, 495 patients who met the criteria were divided into 4 groups based on their BG level and diabetes mellitus (DM) status. The risks for all-cause mortality in each group were assessed using the multivariate Cox proportional hazards model. RESULTS: At a median follow-up of 1.8 years, 148 patients had died. There were 168 patients without either BG elevation or DM, 67 without BG elevation but with DM, 105 with BG elevation but not DM, and 155 with both BG elevation and DM. In a multivariate model, those with BG elevation, regardless of DM status, showed a greater risk of increased mortality when compared with patients without either BG elevation or DM [hazard ratio (HR), 1.79; p=0.042 for BG elevation without DM and HR, 1.73; p=0.048 for BG elevation with DM]. CONCLUSION: Elevated BG levels, irrespective of the DM status, at the time of admission in patients with ADHF, appear to be a prognostic marker for ADHF. PMID- 27554051 TI - Contribution of FcERI-associated vesicles to mast cell-macrophage communication following Francisella tularensis infection. AB - Understanding innate immune intercellular communication following microbial infection remains a key biological issue. Using live cell imaging, we demonstrate that mast cells actively extend cellular projections to sample the macrophage periphery during Francisella tularensis LVS infection. Mast cell MHCII(hi) expression was elevated from less than 1% to 13% during LVS infection. Direct contact during co-culture with macrophages further increased mast cell MHCII(hi) expression to approximately 87%. Confocal analyses of the cellular perimeter revealed mast cell caspase-1 was localized in close proximity with FcERI in uninfected mast cells, and repositioned to clustered regions upon LVS infection. Importantly, mast cell FcERI-encompassed vesicles are transferred to macrophages by trogocytosis, and macrophage caspase-1 expression is further up-regulated upon direct contact with mast cells. Our study reveals direct cellular interactions between innate cells that may impact the function of caspase-1, a known sensor of microbial danger and requirement for innate defense against many pathogenic microbes including F. tularensis. PMID- 27554052 TI - IL-21 inhibits IL-17A-producing gammadelta T-cell response after infection with Bacillus Calmette-Guerin via induction of apoptosis. AB - Innate gammadelta T cells expressing Vgamma6 produce IL-17A at an early stage following infection with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In this study, we used IL-21 receptor knockout (IL-21R KO) mice and IL-21-producing recombinant BCG mice (rBCG-Ag85B-IL-21) to examine the role of IL-21 in the regulation of IL-17A-producing innate gammadelta T-cell response following BCG infection. IL-17A-producing Vgamma6+ gammadelta T cells increased in the peritoneal cavity of IL-21R KO mice more than in wild type mice after BCG infection. In contrast, the number of IL-17A-producing Vgamma6+ gammadelta T cells was significantly lower after inoculation with rBCG-Ag85B-IL-21 compared with control rBCG-Ag85B. Notably, exogenous IL-21 selectively induced apoptosis of IL-17A-producing Vgamma6+ gammadelta T cells via Bim. Thus, these results suggest that IL-21 acts as a potent inhibitor of a IL-17A-producing gammadelta T cell subset during BCG infection. PMID- 27554053 TI - Pain perception in healthy volunteers: effect of repeated exposure to experimental systemic inflammation. AB - We aimed to study the relationship between pain perception and cytokine release during systemic inflammation. We present a randomized crossover trial in healthy volunteers (n = 17) in 37 individual trials. Systemic inflammation was induced by an i.v. bolus of Escherichia coli LPS (2 ng/kg) on two separate trial days, with or without a nicotine patch applied 10 h previously. Pain perception at baseline, and 2 and 6 h after LPS was assessed by pressure algometry and tonic heat stimulation at an increasing temperature (45-48C) during both trials. Compared with baseline, pain pressure threshold was reduced 2 and 6 h after LPS, while heat pain perception was accentuated at all testing temperatures after 2 but not 6 h. The magnitude of changes in pain perception did not correlate to cytokine release. No effect of transdermal nicotine or training status was observed. In conclusion, LPS administration in healthy human volunteers leads to reduction in pain pressure threshold and an increase in pain perception to heat stimuli, supporting a relationship between acute systemic inflammation and pain perception. PMID- 27554054 TI - Plasma contributes to the antimicrobial activity of whole blood against Mycobacterium tuberculosis. AB - The whole blood model for infection has proven useful to analyze the immunological response to Mycobacterium tuberculosis, because it exerts a significant antimicrobial activity. Although this activity has been generally assumed to be cellular, we have found that the leukocyte fraction of blood from healthy volunteers did not kill the bacilli. We have discovered that plasma was responsible for a large proportion, but not all, of the antimicrobial activity. Furthermore, infected monocytes controlled the mycobacterial multiplication when cultivated in the presence of plasma. Intriguingly, serum from the same donors did not share this activity, although it was able to eliminate the non-pathogenic Mycobacterium gordonae To identify the remaining components that participate in the antimycobacterial activity we fractionated blood in leukocytes, plasma, erythrocytes and platelets, and analyzed the bactericidal power of each fraction and their combinations using a factorial design. We found that erythrocytes, but not platelets, participated and showed by flow cytometry that mycobacteria physically associated with erythrocytes. We propose that in exposed healthy individuals that show 'early clearance' of the mycobacteria, the innate response is predominantly humoral, probably through the effect of antimicrobial peptides and proteins. PMID- 27554055 TI - Asparagine improves intestinal integrity, inhibits TLR4 and NOD signaling, and differently regulates p38 and ERK1/2 signaling in weanling piglets after LPS challenge. AB - Asparagine (Asn), an activator of ornithine decarboxylase (ODC), stimulates cell proliferation in intestinal epithelial cells. We hypothesized that Asn can mitigate LPS-induced injury of intestinal structure and barrier function by regulating inflammatory signaling pathways. We executed the following experiment using weanling pigs for each of the groups: (1) non-challenged control; (2) LPS challenged control; (3) LPS + 0.5% Asn; (4) LPS + 1.0% Asn. After 21-d feeding, pigs received an i.p. injection of either saline or LPS. Four h after injection, the mid-jejunum and mid-ileum samples were collected. We found that Asn restored ODC expression that was decreased by LPS treatment. Asn also restored intestinal morphology and barrier function that were impaired by LPS treatment. In addition, Asn down-regulated intestinal caspase-3 protein expression and TNF-alpha concentration, and decreased the mRNA expression of intestinal TLR4, TLR4 downstream signals (myeloid differentiation factor 88, IL-1 receptor-associated kinase 1 and TNF-alpha receptor-associated factor 6 and NOD1, NOD2 and their adaptor molecule (receptor-interacting serine/threonine-protein kinase 2). Moreover, Asn decreased p38 phosphorylation but increased ERK1/2 phosphorylation. Our results suggest that Asn improves intestinal integrity during an inflammatory insult, which appears to be related to the decrease of intestinal pro inflammatory cytokine (via TLR4, NODs and p38) and of enterocyte apoptosis (via p38 and ERK1/2). PMID- 27554056 TI - Normalization of human RNA-seq experiments using chimpanzee RNA as a spike-in standard. AB - Normalization of human RNA-seq experiments employing chimpanzee RNA as a spike-in standard is reported. Human and chimpanzee RNAs exhibit single nucleotide variations (SNVs) in average 210-bp intervals. Spike-in chimpanzee RNA would behave the same as the human counterparts during the whole NGS procedures owing to the high sequence similarity. After discrimination of species origins of the NGS reads based on SNVs, the chimpanzee reads were used to read-by-read normalize biases and variations of human reads. By this approach, as many as 10,119 transcripts were simultaneously normalized for the entire NGS procedures leading to accurate and reproducible quantification of differential gene expression. In addition, incomparable data sets from different in-process degradations or from different library preparation methods were made well comparable by the normalization. Based on these results, we expect that the normalization approaches using near neighbor genomes as internal standards could be employed as a standard protocol, which will improve both accuracy and comparability of NGS results across different sample batches, laboratories and NGS platforms. PMID- 27554057 TI - Symmetry Breaking in Chiral Ionic Liquids Evidenced by Vibrational Optical Activity. AB - Ionic liquids (ILs) are receiving increasing interest for their use in synthetic laboratories and industry. Being composed of charged entities, they show a complex and widely unexplored dynamic behavior. Chiral ionic liquids (CILs) have a high potential as solvents for use in asymmetric synthesis. Chiroptical methods, owing to their sensitivity towards molecular conformation, offer unique possibilities to study the structure of these chiral ionic liquids. Raman optical activity proved particularly useful to study ionic liquids composed of amino acids and the achiral 1-ethyl-3-methylimidazolium counterion. We could substantiate, supported by selected theoretical methods, that the achiral counterion adopts an overall chiral conformation in the presence of chiral amino acid ions. These findings suggest that in the design of chiral ionic liquids for asymmetric synthesis, the structure of the achiral counter ion also has to be carefully considered. PMID- 27554059 TI - Evidence on scleral contact lenses and intraocular pressure. PMID- 27554058 TI - Cytosolic phospholipase A2alpha increases proliferation and de-differentiation of human renal tubular epithelial cells. AB - The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2alpha) enzyme controls the release of arachidonic acid from membrane bound phospholipids and is the rate-limiting step in production of eicosanoids. A variety of different kidney injuries activate cPLA2alpha, therefore we hypothesized that cPLA2alpha activity would regulate pathologic processes in HK-2 cells, a human renal tubular epithelial cell line, by regulating cell phenotype and proliferation. In two lentiviral cPLA2alpha-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells. cPLA2alpha-silenced cells also demonstrated an altered morphology, had increased expression E-cadherin, and decreased expression of Ncadherin. Increased levels of E-cadherin were associated with increased promoter activity and decreased levels of SNAIL1, SNAIL2, and ZEB1, transcriptional repressors of E-cadherin expression. Addition of exogenous arachidonic acid, but not PGE2, reversed the phenotypic changes in cPLA2alpha silenced cells. These data suggest that cPLA2alpha may play a key role in renal repair after injury through a PGE2-independent mechanism. PMID- 27554060 TI - Development of a Comprehensive Clinical Radiation Oncology Resident Didactic Curriculum. PMID- 27554061 TI - International Perspectives on Radiology in Preventive Screening. AB - Several years ago, the International Economics Committee of the ACR began a study of comparisons among nations regarding the practice of radiology. This article is the second in a series. The purpose here is to compare the use across countries of imaging modalities in the screening algorithms of a variety of common diseases. In conjunction with the initial study, this will allow radiologists to understand in greater detail how health system practices differ among a selected set of nations. In this study, a standardized survey was administered to committee members from 10 countries in the developed and developing world. As with the prior study, there were both striking differences and similarities, even among a small cohort of nations that are all (except India) members of the Organisation for Economic Co-operation and Development. For example, breast cancer screening with mammography involves similar radiographic techniques for screening evaluations and has similarly high levels of insurance coverage, but the recommended ages at initial screening and end of screening differ. Other diseases, such as lung cancer and abdominal aortic aneurysm, have variable, but overall lower, levels of estimated participation among surveyed countries and significantly lower insurance coverage. Although this data set relies on survey data from individual practitioners, it provides an important perspective of the role of radiology in screening programs. Given the increasing pressure from domestic and foreign governments to reign in health care costs, the comparative differences in screening programs, and especially their use of (often costly) imaging techniques, may be a harbinger for future health policy decisions in the United States and abroad. PMID- 27554062 TI - Teaching and Working With Millennial Trainees: Impact on Radiological Education and Work Performance. AB - Many feel that the generational differences encountered with Millennial trainees are novel; the reality is that prior generations have always bemoaned generational differences. This is not a new problem; some of the same things may even have been said about us during our own training! There are a variety of myths and misconceptions about the Millennial generation (also known as Generation Y). In this article we review some of the differences frequently encountered as we educate and work alongside our Millennial colleagues, dispelling some of the myths and misconceptions. With increased understanding of this talented group of individuals, we hope to be more effective teachers and have more successful professional relationships. PMID- 27554063 TI - First application of a transcutaneous optical single-port glucose monitoring device in patients with type 1 diabetes mellitus. AB - The combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion can be used to improve the treatment of patients with diabetes. The aim of this study was to advance an existing preclinical single-port system for clinical application by integrating the sensors of a phosphorescence based CGM system into a standard insulin infusion set. The extracorporeal optical phase fluorimeter was miniaturised and is now comparable with commercial CGM systems regarding size, weight and wear comfort. Sensor chemistry was adapted to improve the adhesion of the sensor elements on the insulin infusion set. In-vitro tests showed a linear correlation of R2=0.998 between sensor values and reference glucose values in the range of 0-300mg/dl. Electrical and cytotoxicity tests showed no negative impact on human health. Two single-port devices were tested in each of 12 patients with type 1 diabetes mellitus in a clinical set-up for 12h. Without additional data processing, the overall median absolute relative difference (median ARD) was 22.5%. For some of the used devices the median ARD was even well below 10%. The present results show that individual glucose sensors performance of the single-port system is comparable with commercial CGM systems but further improvements are needed. The new system offers a high extent of safety and usability by combining insulin infusion and continuous glucose measurement in a single-port system which could become a central element in an artificial pancreas for an improved treatment of patients with type 1 diabetes mellitus. PMID- 27554064 TI - Electric field control of magnon-induced magnetization dynamics in multiferroics. AB - We consider theoretically the effect of an inhomogeneous magnetoelectric coupling on the magnon-induced dynamics of a ferromagnet. The magnon-mediated magnetoelectric torque affects both the homogeneous magnetization and magnon driven domain wall motion. In the domains, we predict a reorientation of the magnetization, controllable by the applied electric field, which is almost an order of magnitude larger than that observed in other physical systems via the same mechanism. The applied electric field can also be used to tune the domain wall speed and direction of motion in a linear fashion, producing domain wall velocities several times the zero field velocity. These results show that multiferroic systems offer a promising arena to achieve low-dissipation magnetization rotation and domain wall motion by exciting spin-waves. PMID- 27554065 TI - Role of Metal Oxide Electron-Transport Layer Modification on the Stability of High Performing Perovskite Solar Cells. AB - Organic-inorganic hybrid perovskite light absorbers have recently emerged as a "holy grail" for next generation thin-film photovoltaics with excellent optoelectronics properties and low fabrication cost. In a very short span of time, we have witnessed a pronounced and unexpected progress in organic- inorganic perovskite solar cells (PSCs) with a vertical rise in power conversion efficiency from 3.8 to 22.1 %. In this manuscript we focus specifically on the recent development of metal oxide-based electron-transporting layer (ETL) modification for high performing PSCs and their stability. This review highlights various methodologies to modify existing compact/scaffold layers for improving device performance and stability. Various aspects of the ETL are discussed with different metal oxide compact layers in their relation to modification in mesoporous layers towards the design of a cell structure with high performance and stability. PMID- 27554066 TI - Evolutionary and Expression Analysis Provides Evidence for the Plant Glutamate like Receptors Family is Involved in Woody Growth-related Function. AB - Glutamate-like receptors (GLRs) is a highly conserved family of ligand-gated ion channels, which have been associated with various physiological and developmental processes. Here, we investigated the evolutionary pattern of GLRs in plants. We observed that tandem duplications occupied the largest proportion of the plant GLR gene family expansion. Based on a phylogenetic tree, we suggested a new subfamily, GLR4, which is widespread in angiosperm but absence on Brassicales. Meanwhile, because GLR1 and GLR2 subfamilies were potential sister clades, we combined them into the GLR1&2 subfamily. A comparative analysis of plant GLR subfamilies revealed that selective forces shaped the GLR1&2 repertoires in the stems of eudicotyledons with distinct functional preferences. Moreover, GLR1&2 formed a species-specific highwoody-expanded subfamily, with preferential expression in the cambial-enriched and shoot apical meristem fractions of the highwood species. Together, these findings lay the foundation for evolutionary analysis of plant GLRs over the entire plant timescale and identified unique targets for manipulating the woody-growth behaviours of plant GLRs. PMID- 27554067 TI - Cyclobuteno[60]fullerenes as Efficient n-Type Organic Semiconductors. AB - Cyclobuteno[3,4:1,2][60]fullerenes have been prepared in a straightforward manner by a simple reaction between [60]fullerene and readily available allenoates or alkynoates as organic reagents under basic and mild conditions. The chemical structure of the new modified fullerenes has been determined by standard spectroscopic techniques and confirmed by X-ray diffraction analysis. Some of these new fullerene derivatives exhibit a remarkable intrinsic electron mobility (determined by using flash-photolysis time-resolved microwave conductivity (FP TRMC) measurements), which surpasses that of the well-known phenyl-C61-butyric acid methyl ester, thus behaving as promising n-type organic semiconductors. PMID- 27554068 TI - Microvascular Injury and Perfusion Changes Induced by Ultrasound and Microbubbles in a Machine-Perfused Pig Liver. AB - Localized drug delivery and uptake can benefit from the combined action of ultrasound and microbubbles at a specific site. Some of the possible mechanisms suggested are vessel poration and/or cell poration, but the exact acoustic parameters that trigger those phenomena remain unknown. Ex vivo machine perfusion of human-sized organs is a technique that provides an ideal environment for pre clinical investigations with high physiologic relevance not possible with in vitro experiments. In this work, ex vivo machine-perfused pig livers were combined with an image-guided therapy system to investigate microvascular flow changes caused by the interaction of ultrasound-driven microbubbles with the vasculature. The effects of acoustic pressure (1.7-4 MPa peak negative pressures) and number of cycles (1000 or 20 cycles) were examined. Perfusion changes caused by the action of ultrasound on microbubbles in the microcirculation were qualitatively and quantitatively assessed with contrast-enhanced ultrasound and used as a metric of the extent of vessel perforation, thus, extravasation. Areas that were exposed to peak negative pressures above 1.7 MPa underwent a detectable and irreversible perfusion change. Complete devascularization of the area exposed to ultrasound was observed at much larger acoustic pressures (~4 MPa). Shorter acoustic pulses (20 cycles) produced markedly fewer perfusion changes than longer pulses (1000 cycles) under the same acoustic amplitude exposure. PMID- 27554069 TI - High-Resolution Ultrasound of Schwannomas of the Limbs: Analysis of 72 Cases. AB - Schwannomas are common benign tumors that develop in peripheral nerves. High resolution ultrasound (HRUS) is an effective imaging modality in clinics. The aim of this study was to define the value of HRUS in diagnosing schwannomas that originate from different nerves in limbs. We reviewed the ultrasound and surgical records of 72 pathologically confirmed schwannomas in the limbs of 60 patients. Results revealed that 44 (61.1%) of 72 cases, 44 (75.9%) of 58 cases and 0 (0%) of 14 cases received an overall correct pre-operative diagnosis, a correct pre operative diagnosis in nerve trunks and a correct pre-operative diagnosis in small branches, respectively. Identification of the nerve of origin of schwannomas through HRUS likely increased confidence in diagnosing these benign tumors. PMID- 27554070 TI - Correlation of Breast Ultrasound Classifications with Breast Cancer in Chinese Women. AB - The aim of this study was to identify potential links between ultrasonographic breast parenchymal patterns and the risk of breast cancer in Chinese women. The population of Chinese women at high risk for breast cancer was explored using the ultrasonographic classification. Ultrasonographic parenchymal patterns were classified into four types: heterogeneous type, ductal type, mixed type and fibrous type. A total of 5879 Chinese women underwent breast ultrasound examination from May 2010 to April 2014. Of the 5879 women, 256 women had pathology-confirmed breast cancer. Among the remaining 5623 women, 512 randomly selected, age-matched women were recruited into the present study. The correlation between ultrasonographic type and breast cancer revealed that the odds ratio (OR) was highest for the heterogeneous type (odds ratio = 4.11, 95% confidence interval: 2.01-8.41, p < 0.001), followed by the fibrous type (odds ratio = 2.05, 95% confidence interval: 1.51-2.78, p < 0.001). The odds ratios of the ductal and mixed types were both less than 1 (p < 0.05). This study indicates that the heterogeneous and fibrous types in the ultrasonographic classification are associated with an increased risk of breast cancer and, therefore, can be used as a marker of breast cancer risk in the female population of China. PMID- 27554071 TI - Workplace managers' view of the role of co-workers in return-to-work. AB - PURPOSE: Theoretical and empirical research findings attest to the workplace being a social environment in which co-workers have a critical influence on the employment outcomes and return-to-work (RTW) success of other employees. However, co-workers do not have a formal role in RTW planning. The aim of this study was to explore how managers responsible for developing and implementing RTW procedures view the role of co-workers in this process. METHOD: An exploratory qualitative pilot study was conducted in Canada. Participants (1 male; 13 females; mean experience in RTW = 11.8 years) were workplace (n=8) or RTW managers (n=6) with direct oversight of RTW plans. The participants were recruited via invitation from a research institute and were drawn from three different provinces. Data were gathered via open-ended questions and were coded and subject to thematic analysis. FINDINGS: Three key themes were identified: (1) Managers view RTW as having little relevance to co-workers but expect them to cooperate with the arrangements; (2) Formal procedures are inadequate when psychosocial barriers to work resumption are present, so managers use informal strategies to engage co-workers' emotional and social support; and (3) Managers have difficulty integrating RTW procedures with other legal obligations, such as privacy and confidentiality requirements. CONCLUSION: Existing arrangements for the development and implementation of RTW are sufficient most of the time, but may be inadequate when an injured worker presents with psychosocial barriers to work resumption. Implications for Rehabilitation Standard RTW arrangements can be inadequate when a RTW plan requires active co-worker support. Privacy and confidentiality provisions can result in managers using informal procedures for information exchange and to engage co-workers. The use of risk management strategies - assessment, consultation and communication - could be used to include co-workers when workplace issues threaten the success of a RTW plan. PMID- 27554072 TI - Development of Abnormal Hemispheric Vascular Networks Mimicking Cerebral Proliferative Angiopathy in a Child Originally Diagnosed with Deep-Seated Arteriovenous Fistula. AB - Cerebral proliferative angiopathy (CPA), which is characterized by diffuse vascular abnormalities with intermingled normal brain parenchyma, is a rare clinical entity distinct from classical cerebral arteriovenous malformations. Its pathology at initial state and subsequent course of progression has totally been undetermined. We herein presented a case of a child who was initially diagnosed with deep-seated arteriovenous fistula (AVF), and ultimately developed symptomatic CPA-like vascular lesion over a long period of clinical follow-up. A 7-month-old boy was incidentally found to have an AVF in the right basal ganglia and conservatively followed up. Serial magnetic resonance angiograms revealed the gradual proliferation and enlargement of pial and medullary vessels surrounding the AVF. Seven years later, he had a transient ischemic attack followed by intraventricular hemorrhage. A catheter angiogram showed a diffuse large vascular malformation composed of 2 distinct structures, including AVF in the right basal ganglia and the surrounding proliferated pial and medullary arteries in the right hemisphere. Single-photon emission computed tomography with N-isopropyl[123I]-p iodoamphetamine revealed apparent hemodynamic compromise on the right hemisphere. Targeted embolization of the pseudoaneurysm originating from the right A1 perforator was performed to prevent rebleeding without complications. The patient had no further cerebrovascular events. Perinidal hypoperfusion induced by a deep seated AVF could be one of the underlying pathologies of progressive angiogenic activity. This is the first case showing the development of abnormal hemispheric vascular networks mimicking CPA, which offers insight into the pathogenesis of this new entity. PMID- 27554073 TI - Aerobic Exercises for Cognition Rehabilitation following Stroke: A Systematic Review. AB - BACKGROUND: Cognitive impairments are highly prevalent in stroke survivors and can substantially affect their physical rehabilitation and quality of life. The management of these impairments currently remains limited, but increasing studies reported the effect of aerobic exercise on cognitive performance in patients suffering from stroke. The purpose of this review was to assess the effects of aerobic exercise on cognitive function following stroke. METHODS: Seven electronic databases (China National Knowledge Infrastructure [CNKI], Chinese Science and Technology Periodical Database [VIP], Wanfang, China Biology Medicine disc [CBM], Science Citation Index [SCI], EMBASE, and PubMed) were searched from their inception to May 31, 2015, for the effects of aerobic exercise on cognitive ability compared to usual physical activity in stroke survivors. RevMan V5.3 (The Nordic Cochrane Centre) was used to analyze the data and to evaluate the methodological quality of the included studies. RESULTS: Ten eligible studies including 394 participants were identified. Six studies showed that aerobic exercise significantly improved global cognitive ability in stroke survivors. Four studies reported aerobic exercise to be beneficial in improving memory, but only one showed statistical significance. Two studies investigated the effects of aerobic exercise on attention, and one showed a significant improvement. One study reported a significant benefit of aerobic exercise on visuospatial ability in stroke survivors. No adverse events were reported in the included studies. CONCLUSIONS: Aerobic exercise may have a positive effect on improving global cognitive ability and a potential benefit on memory, attention, and the visuospatial domain of cognition in stroke survivors. However, further large, rigorously designed trials are needed to confirm these findings. PMID- 27554074 TI - Prediction of Ischemic Stroke-Associated Pneumonia: A Comparison between 3 Scores. AB - BACKGROUND: Stroke is a leading cause of death and disability worldwide. Among all poststroke complications, pneumonia constitutes a major complication with a strong impact on morbidity and mortality. To identify patients at high risk of stroke-associated pneumonia (SAP) and to tailor a prophylactic approach, a reliable scoring model for prediction may be useful in daily stroke care. OBJECTIVES: This study aimed to compare the performance of the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity (A2DS2) score, the acute ischemic stroke-associated pneumonia score (AIS-APS), and the Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) score in predicting SAP. METHODS: Seventy consecutive patients with ischemic stroke admitted to the Critical Care Medicine Department of Alexandria Main University Hospital were included. Patients were prospectively followed up for primary outcome of pneumonia within the first 7 days after admission diagnosed by the Centers for Disease Control and Prevention criteria. Accuracy in predicting outcome measures was assessed by calculating the area under receiver operating characteristic curve (AUC). RESULTS: Twenty-six (37.1%) patients developed pneumonia by the seventh day; the A2DS2 score AUC was .847 (95% CI: .741-.922), and the AIS-APS AUC was .798 (95% CI: .685-.884). The PANTHERIS score AUC was .715 (95% CI: .595-.817). The A2DS2 score AUC was significantly higher than the AIS-APS and the PANTHERIS score AUCs (P = .048 and P = .009 respectively), and the AIS-APS AUC was significantly higher than the PANTHERIS score AUC (P = .044). CONCLUSIONS: The A2DS2 score is a valid tool for the prediction of SAP based on routinely collected data, and among the 3 studied scores, it shows the best performance in predicting SAP. PMID- 27554075 TI - Independent Correlation of Serum Homocysteine with Cerebral Microbleeds in Patients with Acute Ischemic Stroke due to Large-Artery Atherosclerosis. AB - BACKGROUND AND AIM: The severity of cerebral microbleeds (CMBs) affected the prognosis of patients with acute cerebrovascular disease. Considering the impact of CMBs on clinical decision, it is necessary to assess the risk factors of CMBs. We aimed to evaluate the independent risk factors of CMBs in patients with acute ischemic stroke of large-artery atherosclerosis. MATERIALS AND METHODS: 112 patients were enrolled in the study. The baseline information, the results of laboratory examination and cranial MRI were collected. The independent risk factors of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis were evaluated. RESULTS: CMBs were found in 56 (50%) patients. Older age and higher homocysteine (Hcy) level were associated with an elevated chance of occurrence of CMBs. Further, there was a positive correlation between CMBs grade and serum Hcy level. CONCLUSIONS: Serum Hcy level is strongly associated with the presence of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis. Serum Hcy level may be a potential therapeutic target for alleviating adverse clinical outcomes of CMBs. PMID- 27554076 TI - Serum Immune Mediators Independently Associate with Atherosclerosis in the Left (But Not Right) Carotid Territory of Older Individuals. AB - BACKGROUND AND AIM: Disturbance in the carotid arteries strongly predicts cerebrovascular events and correlates with a systemic inflammatory milieu. We investigated the relationship of a profile of 10 circulating inflammatory mediators with measures of carotid intima-media thickness (cIMT) in elderly subjects, taking traditional risk factors into account. METHODS: Clinical inspection for present and past chronic conditions and events, as well as biochemical and anthropometric measurements, was performed for patients in ambulatory setting. Scores of cIMT were obtained bilaterally in the distal common carotid artery wall. Serum concentrations of cytokines were assessed by bead based, multiplexed flow cytometry immunoassays. RESULTS: Correlation analysis between log-transformed cytokines levels implicated the mediators interleukin 1beta (IL1beta), IL6, IL8, IL10, and tumor necrosis factor-alpha (TNFalpha) (P <= .005) with scores of the left cIMT. Stepwise multivariate regression showed that TNFalpha, IL1beta, and IL6 levels accounted for most of the variance in the cIMT scores. Comparison of cytokine levels across increasing tertiles of the left cIMT reproduced the positive association with TNFalpha and IL1beta levels. CONCLUSION: Five out of ten immune mediators independently correlated with cIMT of older subjects in a territory-sensitive manner. This possible contribution of immune mediators to an atherosclerotic process probably relates to the inflammaging process. PMID- 27554077 TI - Self-management program for chronic low back pain: A systematic review and meta analysis. AB - OBJECTIVE: To determine the effectiveness of self-management programs (SMPs) on chronic low back pain (CLBP). METHODS: A search of randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Web of Science, Elsevier, and CINAHL through June, 2015. Two reviewers selected trials, conducted critical appraisal, and extracted data. Meta analyses were performed. RESULTS: Thirteen moderate-quality RCTs were included. There were 9 RCTs for immediate post intervention on pain intensity and disability, 5 RCTs for short term, 3 RCTs for intermediate and 4 RCTs for long term. Specifically, the effect sizes (ESs) of SMP on pain intensity were -0.29, -0.20, -0.23, and -0.25 at immediate post intervention, short-term, intermediate-term, and long-term follow-ups, respectively. The ESs on disability were -0.28, -0.23, -0.19, and -0.19 at immediate post-intervention, short-term, intermediate-term, and long-term follow ups, respectively. CONCLUSION: For CLBP patients, there is moderate-quality evidence that SMP has a moderate effect on pain intensity, and small to moderate effect on disability. PRACTICE IMPLICATIONS: SMP can be regarded as an effective approach for CLBP management. In addition to face-to-face mode, internet-based strategy can also be considered as a useful option to deliver SMP. Theoretically driven programs are preferred. PMID- 27554078 TI - Are People Interested in Probabilities of Natural Disasters? AB - Previous research has demonstrated that in naturalistic risky decisions people tend to have little interest in receiving information about probabilities. The present research asked whether subjects search for and employ probabilistic information in situations that are representative of natural disasters: namely, situations where (1) they have no control over the occurrence of a negative event and (2) there might be huge losses of physical and human capital. Pseudo realistic scenarios involving risky situations were presented to 116 experimental participants. Based on the active information search paradigm, subjects were given only a basic description of the situation and had to acquire additional information from the experimenter. In addition to the main task, the individual risk aversion of participants was measured. We demonstrate that in pseudo naturalistic scenarios involving natural disasters people tend to show more interest in probabilities compared to scenarios with generally more controllable risks. Moreover, this interest increases with an increase in the importance of the situation to the decisionmaker. The importance of the situation also has a positive influence on the thoroughness of information search. The experiment detected no connection between individual risk aversion and information search. PMID- 27554080 TI - [Not Available]. PMID- 27554079 TI - Surgical Replacement of Implantable Pulse Generators in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort. AB - BACKGROUND: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. OBJECTIVE: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. METHODS: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. RESULTS: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). CONCLUSIONS: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements. PMID- 27554081 TI - BRAF V600E mutation in hairy cell leukemia: from bench to bedside. AB - Hairy cell leukemia (HCL) is a distinct clinicopathological entity whose underlying genetic lesion has remained a mystery for over half a century. The BRAF V600E mutation is now recognized as the causal genetic event of HCL because it is somatic, present in the entire tumor clone, detectable in almost all cases at diagnosis (encompassing the whole disease spectrum), and stable at relapse. BRAF V600E leads to the constitutive activation of the RAF-MEK-extracellular signal-regulated kinase (ERK) signaling pathway which represents the key event in the molecular pathogenesis of HCL. KLF2 and CDNK1B (p27) mutations may cooperate with BRAF V600E in promoting leukemic transformation. Sensitive molecular assays for detecting BRAF V600E allow HCL (highly responsive to purine analogs) to be better distinguished from HCL-like disorders, which are treated differently. In vitro preclinical studies on purified HCL cells proved that BRAF and MEK inhibitors can induce marked dephosphorylation of MEK/ERK, silencing of RAF-MEK ERK pathway transcriptional output, loss of the HCL-specific gene expression profile signature, change of morphology from "hairy" to "smooth," and eventually apoptosis. The overall response rate of refractory/relapsed HCL patients to the BRAF inhibitor vemurafenib approached 100%, with 35% to 40% complete remissions (CRs). The median relapse free-survival was about 19 months in patients who had achieved CR and 6 months in those who had obtained a partial response. Future therapeutic perspectives include: (1) combining BRAF inhibitors with MEK inhibitors or immunotherapy (anti-CD20 monoclonal antibody) to increase the percentage of CRs and (2) better understanding of the molecular mechanisms underlying resistance of HCL cells to BRAF inhibitors. PMID- 27554083 TI - N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. AB - Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. However, the molecular mechanisms underlying VWF clearance remain poorly understood. In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. Indeed, loss of the N glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo. PMID- 27554082 TI - In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors. AB - Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35++) vector system. These vectors target CD46, a receptor that is uniformly expressed on HSPCs. We demonstrated in human CD46 transgenic mice and immunodeficient mice with engrafted human CD34+ cells that HSPCs transduced in the periphery home back to the BM where they stably express the transgene. In hCD46 transgenic mice, we showed that our in vivo HSPC transduction approach allows for the stable transduction of primitive HSPCs. Twenty weeks after in vivo transduction, green fluorescent protein (GFP) marking in BM HSPCs (Lin-Sca1+Kit- cells) in most of the mice was in the range of 5% to 10%. The percentage of GFP-expressing primitive HSPCs capable of forming multilineage progenitor colonies (colony forming units [CFUs]) increased from 4% of all CFUs at week 4 to 16% at week 12, indicating transduction and expansion of long-term surviving HSPCs. Our approach was well tolerated, did not result in significant transduction of nonhematopoietic tissues, and was not associated with genotoxicty. The ability to stably genetically modify HSPCs without the need of myeloablative conditioning is relevant for a broader clinical application of gene therapy. PMID- 27554084 TI - Biomarkers defining the metabolic age of red blood cells during cold storage. AB - Metabolomic investigations of packed red blood cells (RBCs) stored under refrigerated conditions in saline adenine glucose mannitol (SAGM) additives have revealed the presence of 3 distinct metabolic phases, occurring on days 0-10, 10 18, and after day 18 of storage. Here we used receiving operating characteristics curve analysis to identify biomarkers that can differentiate between the 3 metabolic states. We first recruited 24 donors and analyzed 308 samples coming from RBC concentrates stored in SAGM and additive solution 3. We found that 8 extracellular compounds (lactic acid, nicotinamide, 5-oxoproline, xanthine, hypoxanthine, glucose, malic acid, and adenine) form the basis for an accurate classification/regression model and are able to differentiate among the metabolic phases. This model was then validated by analyzing an additional 49 samples obtained by preparing 7 new RBC concentrates in SAGM. Despite the technical variability associated with RBC processing strategies, verification of these markers was independently confirmed in 2 separate laboratories with different analytical setups and different sample sets. The 8 compounds proposed here highly correlate with the metabolic age of packed RBCs, and can be prospectively validated as biomarkers of the RBC metabolic lesion. PMID- 27554086 TI - Do women change their breast cancer mammogram screening behaviour after BRCA1/2 testing? AB - Little is known about the change in mammograms use by women after BRCA1/2 genetic testing. We compared the rate of bilateral mammograms after and prior to BRCA1/2 testing, according to test result. Information from the Quebec Health Insurance Board database was used to identify all registered mammograms delivered between May 1, 1998 and March 31, 2012 to a cohort of 396 unaffected French Canadian women tested for BRCA1/2 mutations. Mammograms incidence density ratios were calculated using the Cox proportional hazards model for repeated events. BRCA1/2 mutation carriers and women with an inconclusive result had more mammograms after, than prior to, genetic testing. Non-carriers did not receive more mammograms. The observed increase in mammography screening in BRCA1/2 carriers is consistent with the high risk of developing breast cancer in this group. The estimation of the cancer risk associated with an inconclusive result is based on familial cancer history, and women who received this result appear to have received follow-up as if at high risk. The fact that non-carriers did not change their use of mammograms after genetic testing may possibly reflect a 'defensive medicine' approach by some physicians or the women's preference. PMID- 27554085 TI - Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes. AB - Enhancers are the primary determinants of cell identity, and specific promoter/enhancer combinations of Endoglin (ENG) have been shown to target blood and endothelium in the embryo. Here, we generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by specific promoter/enhancer combinations of ENG, to evaluate their discriminative potential and value as molecular probes of the corresponding transcriptome. The Eng promoter (P) in combination with the -8/+7/+9-kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8-kb enhancer targeted TIE2+/c-KIT+/CD41- endothelial cells that were enriched for hematopoietic potential. These fractions were isolated using reporter expression and their transcriptomes profiled by RNA-seq. There was high concordance between our signatures and those from embryos with defects at corresponding stages of hematopoiesis. Of the 6 genes that were upregulated in both hemogenic mesoderm and hemogenic endothelial fractions targeted by the reporters, LRP2, a multiligand receptor, was the only gene that had not previously been associated with hematopoiesis. We show that LRP2 is indeed involved in definitive hematopoiesis and by doing so validate the use of reporter gene-coupled enhancers as probes to gain insights into transcriptional changes that facilitate cell fate transitions. PMID- 27554087 TI - Inducing ownership over an 'other' perspective with a visuo-tactile manipulation. AB - Seeing our body from a 'self' perspective while performing a movement improves our ability to detect asynchrony between the visual and proprioceptive information concerning that movement: a signature of enhanced body ownership referred to as the 'self-advantage'. We consequently experience no self-advantage when seeing our body from an 'other' perspective. Here we ask whether introducing visuo-tactile stimulation (VTS), similar to that used in the rubber hand illusion to invoke ownership over a dummy hand, would produce a self-advantage when viewing the body from a typically 'other' perspective. Prior to the experiment, participants watched a live video of their own back using a camera mounted behind them while their back was tapped with a rod for 2 min. The video was either synchronous (sVTS) or asynchronous (aVTS) with the tapping. Participants then raised their hands and made a stereotyped finger movement that they watched from the same camera either in the original, natural perspective or upside down. Participants indicated which of two periods (one with minimum delay and one with an added delay of 33-264 ms) appeared delayed. Sensitivity was calculated using psychometric functions. The sVTS group showed a self-advantage of about 45 ms in the natural visual condition compared to the upside down condition, whereas the aVTS group showed no difference between the two conditions. Synchronous visuo tactile experience increased the feeling of ownership over a typically 'other' perspective in a quantifiable way indicating the multisensory and malleable nature of body representation. PMID- 27554088 TI - Pharmacokinetic Properties of Intravenous Ibuprofen in Healthy Chinese Volunteers. AB - BACKGROUND AND OBJECTIVES: No pharmacokinetic data of intravenous ibuprofen were available in a Chinese population and the published information remained inadequate. The present study aimed to investigate the pharmacokinetic properties of intravenous ibuprofen in healthy Chinese volunteers after single- and multiple dose administration. METHODS: Twelve subjects received single doses of 200, 400, and 800 mg intravenous ibuprofen, respectively, and multiple doses of 400 mg intravenous ibuprofen, four times per day (every 6 h) till the morning of the sixth day in each study period. RESULTS: After single doses of 200, 400 and 800 mg and multiple doses of 400 mg intravenous ibuprofen, the main pharmacokinetic parameters obtained were: maximum plasma concentration (C max) 23.05 +/- 2.96, 41.90 +/- 3.22, 76.06 +/- 8.70, and 49.53 +/- 3.92 MUg/ml, respectively, which were achieved immediately at the end of the infusion; area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUC0-t ) 49.82 +/- 10.92, 88.79 +/- 12.43, 152.34 +/- 25.23, and 106.68 +/- 18.94 ug.h/mL, respectively; AUC from time zero to infinity (AUC0 infinity) 51.91 +/- 10.67, 91.46 +/- 12.06, 155.04 +/- 25.70, and 108.58 +/- 19.49 ug.h/ml, respectively; half-life (t 1/2) 1.87 +/- 0.30, 1.93 +/- 0.24, 2.02 +/- 0.38, and 1.74 +/- 0.26 h, respectively. The accumulation index (AI) was 1.22 +/- 0.17 after multiple doses. The most obvious accumulation was observed in males; other parameters revealed no significant differences. CONCLUSIONS: Similar pharmacokinetic properties of intravenous ibuprofen in healthy Chinese volunteers were observed to those reported in a Caucasian population. Multiple doses of intravenous ibuprofen every 6 h caused slight accumulation. Except for the AI, sex did not affect the pharmacokinetics of intravenous ibuprofen. CHICTR. ORG IDENTIFIER: ChiCTR-IIR-15007347. PMID- 27554089 TI - The impact of different types of parental support behaviours on child physical activity, healthy eating, and screen time: a cross-sectional study. AB - BACKGROUND: In Canada, 31.5 % of children are overweight or obese, putting them at an increased risk of chronic co-morbidities and premature mortality. Physical activity, healthy eating, and screen time are important behavioural determinants of childhood overweight and obesity that are influenced by the family environment, and particularly parents' support behaviours. However, there is currently a limited understanding of which types of these support behaviours have the greatest positive impact on healthy child behaviours. This study aims to determine the relative contribution of different types of parental support behaviours for predicting the likelihood that children meet established guidelines for daily physical activity, daily fruit and vegetable consumption, and recreational screen time. METHODS: A Computer Assisted Telephone Interview survey was used to collect data from a random sample of parents or guardians with at least one child under the age of 18 in Ontario (n = 3,206). Three multivariable logistic regression models were built to predict whether or not parents reported their child was meeting guidelines. Independent variables included parent and child age and gender, multiple indicators of parental support behaviours, and socio-demographic characteristics. Parental support behaviours were categorized post-hoc as motivational, instrumental, regulatory, and conditional based on an adapted framework. RESULTS: Controlling for all other factors in the model, several parental support behaviours were found to be significant predictors of children meeting established health guidelines. For example, conditional support behaviours including taking the child to places where they can be active (OR: 2.06; 95 % CI: 1.32-3.21), and eating meals as a family away from the TV (95 % CI: 1.15-2.41) were significant positive predictors of children meeting physical activity and fruit and vegetable guidelines, respectively. CONCLUSIONS: Health promotion efforts aimed at improving particular parent support behaviours could be effective levers for mitigating the burden of excess body weight in childhood. As such, the influence of support behaviours should be fully considered in any comprehensive approach to prevention and reduction of childhood overweight and obesity. PMID- 27554090 TI - Diabetic Peripheral Neuropathy as a Predictor of Asymptomatic Myocardial Ischemia in Type 2 Diabetes Mellitus: A Cross-Sectional Study. AB - INTRODUCTION: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and has been associated with cardiovascular disease, the leading cause of mortality in diabetes. As asymptomatic myocardial ischemia (MI) is frequent in diabetes, we hypothesized that DPN may be associated with MI in patients with type 2 diabetes mellitus and no history of cardiovascular events. METHODS: Eighty-two patients with DPN (n = 41) or without DPN (n = 41) were included. Among the DPN group, 15 had active foot ulcers. All subjects underwent Technetium-99 m sestamibi single-photon emission computed tomographic imaging for the estimation of myocardial ischemia, expressed as Summed Stress Score (SSS). The Neuropathy Disability Score (NDS) was used to quantify DPN and abnormal ratio of the longest electrocardiographic RR interval between the 28th and 32nd beats, after standing to the shortest interval between the 13th and 17th beats (RR ratio) was used as an index of cardiovascular autonomic neuropathy (CAN). RESULTS: Abnormal SSS was observed in 9.8% of patients without DPN and in 46.3% of patients with DPN (p < 0.001). In the multivariate analysis, NDS was the strongest predictor for SSS (beta = 0.32, p = 0.003). When excluding patients with abnormal RR ratio (beta = 0.32, p = 0.003) or with foot ulcers (beta = 0.24, p = 0.04), this association remained significant. The RR ratio was also significantly associated with SSS in univariate (rho = -0.30, p = 0.005) and multiple regressions (beta = 0.24, p = 0.02). CONCLUSIONS: MI was strongly associated with DPN, and this association remained significant in patients with normal RR ratio. These results suggest that DPN assessment could help in identifying patients at risk of cardiovascular disease (CVD). PMID- 27554091 TI - Management and Outcome of Periprocedural Cardiac Perforation and Tamponade with Radiofrequency Catheter Ablation of Cardiac Arrhythmias: A Single Medium-Volume Center Experience. AB - INTRODUCTION: Cardiac tamponade (CT) is a life-threatening complication of radiofrequency ablation (RFA). The course and outcome of CT in low-to-medium volume electrophysiology centers are underreported. METHODS: We analyzed the incidence, management and outcomes of CT in 1500 consecutive RFAs performed in our center during 2011-2016. RESULTS: Of 1500 RFAs performed in 1352 patients (age 55 years, interquartile range: 41-63), 569 were left-sided procedures (n = 406 with transseptal access). Conventional RFA or irrigated RFA was performed in 40.9% and 59.1% of procedures, respectively. Ablation was performed mostly for atrioventricular nodal reentrant tachycardia (25.4%), atrial fibrillation (AF; 18.5%), atrial flutter (18.4%), accessory pathway (16.5%) or idiopathic ventricular arrhythmia (VA; 12.3%), and rarely for structural VA (2.1%). CT occurred in 12 procedures (0.8%): 10 AF ablations, 1 idiopathic VA and 1 typical atrial flutter ablation. Factors significantly associated with CT were older age, pre-procedural oral anticoagulation, left-sided procedures, transseptal access, AF ablation, irrigated RFA and longer fluoroscopy time (on univariate analysis), and AF ablation (on multivariable analysis). The perforation site was located in the left atrium (n = 7), right atrium (n = 3), or in the left ventricle or coronary sinus (n = 1 each). Upon pericardiocentesis, two patients underwent urgent cardiac surgery because of continued bleeding. There was no fatal outcome. During the follow-up of 19 +/- 14 months, eight patients were arrhythmia free. CONCLUSION: Incidence of RFA-related CT in our medium-volume center was low and significantly associated with AF ablation. The outcome of CT was mostly favorable after pericardiocentesis, but readily accessible cardiothoracic surgery back-up should be mandatory in RFA centers. PMID- 27554092 TI - Training and evaluation corpora for the extraction of causal relationships encoded in biological expression language (BEL). AB - Success in extracting biological relationships is mainly dependent on the complexity of the task as well as the availability of high-quality training data. Here, we describe the new corpora in the systems biology modeling language BEL for training and testing biological relationship extraction systems that we prepared for the BioCreative V BEL track. BEL was designed to capture relationships not only between proteins or chemicals, but also complex events such as biological processes or disease states. A BEL nanopub is the smallest unit of information and represents a biological relationship with its provenance. In BEL relationships (called BEL statements), the entities are normalized to defined namespaces mainly derived from public repositories, such as sequence databases, MeSH or publicly available ontologies. In the BEL nanopubs, the BEL statements are associated with citation information and supportive evidence such as a text excerpt. To enable the training of extraction tools, we prepared BEL resources and made them available to the community. We selected a subset of these resources focusing on a reduced set of namespaces, namely, human and mouse genes, ChEBI chemicals, MeSH diseases and GO biological processes, as well as relationship types 'increases' and 'decreases'. The published training corpus contains 11 000 BEL statements from over 6000 supportive text excerpts. For method evaluation, we selected and re-annotated two smaller subcorpora containing 100 text excerpts. For this re-annotation, the inter-annotator agreement was measured by the BEL track evaluation environment and resulted in a maximal F score of 91.18% for full statement agreement. In addition, for a set of 100 BEL statements, we do not only provide the gold standard expert annotations, but also text excerpts pre-selected by two automated systems. Those text excerpts were evaluated and manually annotated as true or false supportive in the course of the BioCreative V BEL track task.Database URL: http://wiki.openbel.org/display/BIOC/Datasets. PMID- 27554093 TI - Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma. AB - We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235. PMID- 27554095 TI - Perirectal myxoid pseudocyst removed by transanal endoscopic microsurgery. PMID- 27554094 TI - Glucagon-like peptide-1 analogue, liraglutide, in experimental cerebral malaria: implications for the role of oxidative stress in cerebral malaria. AB - BACKGROUND: Cerebral malaria from Plasmodium falciparum infection is major cause of death in the tropics. The pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ROS/RNS) in the brain is incompletely understood. Insulinotropic glucagon-like peptide-1 (GLP-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ROS/RNS dysfunction. This study investigates the effect of the GLP-1 analogue, liraglutide against the clinical outcome of experimental cerebral malaria (ECM) and Plasmodium falciparum growth. Furthermore the role of oxidative stress on ECM pathogenesis is evaluated. METHODS: ECM was induced in Plasmodium berghei ANKA-infected C57Bl/6j mice. Infected Balb/c (non-cerebral malaria) and uninfected C57Bl/6j mice were included as controls. Mice were treated twice-daily with vehicle or liraglutide (200 MUg/kg). ROS/RNS were quantified with in vivo imaging and further analyzed ex vivo. Brains were assayed for cAMP, activation of cAMP response element binding protein (CREB) and nitrate/nitrite. Plasmodium falciparum was cultivated in vitro with increasing doses of liraglutide and growth and metabolism were quantified. RESULTS: The development and progression of ECM was not affected by liraglutide. Indeed, although ROS/RNS were increased in peripheral organs, ROS/RNS generation was not present in the brain. Interestingly, CREB was activated in the ECM brain and may protect against ROS/RNS stress. Parasite growth was not adversely affected by liraglutide in mice or in P. falciparum cultures indicating safety should not be a concern in type-II diabetics in endemic regions. CONCLUSIONS: Despite the breadth of models where GLP-1 is neuroprotective, ECM was not affected by liraglutide providing important insight into the pathogenesis of ECM. Furthermore, ECM does not induce excess ROS/RNS in the brain potentially associated with activation of the CREB system. PMID- 27554096 TI - Compression versus hand-sewn and stapled anastomosis in colorectal surgery: a systematic review and meta-analysis of randomized controlled trials. AB - Anastomotic leaks are a feared complication of colorectal resections and novel techniques that have the potential to decrease them are still sought. This study aimed to compare the anastomotic leak rates in patients undergoing compression anastomoses versus hand-sewn or stapled anastomoses. Randomized controlled trials (RCTs) comparing outcomes of compression versus conventional (hand-sewn and stapled) colorectal anastomosis were collected from MEDLINE, Embase and the Cochrane Library. The quality of the RCTs and the potential risk of bias were assessed. Pooled odds ratios (OR) were calculated for categorical outcomes and weighted mean differences for continuous data. Ten RCTs were included, comprising 1969 patients (752 sutured, 225 stapled, and 992 compression anastomoses). Most used the biofragmentable anastomotic ring. There was no significant difference between the two groups in terms of anastomotic leak rates (OR 0.80, 95 % confidence interval (CI) 0.47, 1.37; p = 0.42), stricture (OR 0.54: 95 % CI 0.18, 1.64; p = 0.28) or mortality (OR 0.70; 95 % CI 0.39, 1.26; p = 0.24). Compression anastomosis was associated with an earlier return of bowel function: 1.02 (95 % CI 1.37, 0.66) days earlier (p < 0.001) and a shorter postoperative stay; 1.13 (95 % CI 1.52, 0.74) days shorter (p < 0.001), but significant heterogeneity among studies was observed. There was an increased risk of postoperative bowel obstruction in the compression group (OR 1.87; 95 % CI 1.07, 3.26; p = 0.03). There was no significant difference in wound-related and general complications, or length of surgery. Compression devices do not appear to provide an advantage over conventional techniques in fashioning colorectal anastomoses and are associated with an increased risk of bowel obstruction. PMID- 27554097 TI - Advantages of continuous genotype values over genotype classes for GWAS in higher polyploids: a comparative study in hexaploid chrysanthemum. AB - BACKGROUND: Association studies are an essential part of modern plant breeding, but are limited for polyploid crops. The increased number of possible genotype classes complicates the differentiation between them. Available methods are limited with respect to the ploidy level or data producing technologies. While genotype classification is an established noise reduction step in diploids, it gains complexity with increasing ploidy levels. Eventually, the errors produced by misclassifications exceed the benefits of genotype classes. Alternatively, continuous genotype values can be used for association analysis in higher polyploids. We associated continuous genotypes to three different traits and compared the results to the output of the genotype caller SuperMASSA. Linear, Bayesian and partial least squares regression were applied, to determine if the use of continuous genotypes is limited to a specific method. A disease, a flowering and a growth trait with h (2) of 0.51, 0.78 and 0.91 were associated with a hexaploid chrysanthemum genotypes. The data set consisted of 55,825 probes and 228 samples. RESULTS: We were able to detect associating probes using continuous genotypes for multiple traits, using different regression methods. The identified probe sets were overlapping, but not identical between the methods. Baysian regression was the most restrictive method, resulting in ten probes for one trait and none for the others. Linear and partial least squares regression led to numerous associating probes. Association based on genotype classes resulted in similar values, but missed several significant probes. A simulation study was used to successfully validate the number of associating markers. CONCLUSIONS: Association of various phenotypic traits with continuous genotypes is successful with both uni- and multivariate regression methods. Genotype calling does not improve the association and shows no advantages in this study. Instead, use of continuous genotypes simplifies the analysis, saves computational time and results more potential markers. PMID- 27554098 TI - Utility of modified Faine's criteria in diagnosis of leptospirosis. AB - BACKGROUND: Leptospirosis is a globally emerging zoonotic disease and an important public health threat in developing countries. Diagnosis of leptospirosis is mainly based on clinical presentations in resource poor countries. World Health Organization (WHO) has introduced "Faine's criteria" for diagnosis of leptospirosis. This study was conducted to evaluate the usefulness of modified Faine's criteria (with amendment) 2012 to detect leptospirosis in resource poor settings. METHODS: Blood samples of 168 patients who fulfilled the inclusion criteria admitted between January 2013 to January 2014 were tested by a commercial immunochromatographic assay (Leptocheck WB, India), microscopic agglutination test (MAT) and polymerase chain reaction (PCR) methods. Leptospirosis was confirmed by a single MAT titre >=1:400 and / or by a positive PCR. Diagnosis of leptospirosis was made using the clinical, epidemiological and laboratory data according to modified Faine's criteria (with amendment) 2012. RESULTS: Leptospirosis was confirmed in 39 % (n = 66) by MAT and/or PCR. When modified Faine's criteria (MAT >= 1.400 &/ or PCR), was evaluated against LERG confirmed cases sensitivity, specificity, positive predictive value and negative predictive values were 95.45 %, 56.86 %, 58.88 %, 95.08 % respectively. The modified Faine's criteria with rapid immunochromatographic assay only had a sensitivity, specificity, positive predictive value and negative predictive value 89.39 %, 58.82 %, 58.42 %, and 89.55 % respectively. CONCLUSION: The modified Faine's criteria which utilized only immunochromatographic assay (leptocheck IgM) in Part C was found to be useful tool for diagnosing leptospirosis in a resource poor setting. PMID- 27554100 TI - Social Autopsy of maternal, neonatal deaths and stillbirths in rural Bangladesh: qualitative exploration of its effect and community acceptance. AB - OBJECTIVES: Social Autopsy (SA) is an innovative strategy where a trained facilitator leads community groups through a structured, standardised analysis of the physical, environmental, cultural and social factors contributing to a serious, non-fatal health event or death. The discussion stimulated by the formal process of SA determines the causes and suggests preventative measures that are appropriate and achievable in the community. Here we explored individual experiences of SA, including acceptance and participant learning, and its effect on rural communities in Bangladesh. The present study had explored the experiences gained while undertaking SA of maternal and neonatal deaths and stillbirths in rural Bangladesh. DESIGN: Qualitative assessment of documents, observations, focus group discussions, group discussions and in-depth interviews by content and thematic analyses. RESULTS: Each community's maternal and neonatal death was a unique, sad story. SA undertaken by government field-level health workers were well accepted by rural communities. SA had the capability to explore the social reasons behind the medical cause of the death without apportioning blame to any individual or group. SA was a useful instrument to raise awareness and encourage community responses to errors within the society that contributed to the death. People participating in SA showed commitment to future preventative measures and devised their own solutions for the future prevention of maternal and neonatal deaths. CONCLUSIONS: SA highlights societal errors and promotes discussion around maternal or newborn death. SA is an effective means to deliver important preventative messages and to sensitise the community to death issues. Importantly, the community itself is enabled to devise future strategies to avert future maternal and neonatal deaths in Bangladesh. PMID- 27554099 TI - The anti-arthritic, anti-inflammatory, antioxidant activity and relationships with total phenolics and total flavonoids of nine South African plants used traditionally to treat arthritis. AB - BACKGROUND: Oxidative stress predisposes the human and animal body to diseases like cancer, diabetes, arthritis, rheumatoid arthritis, atherosclerosis and chronic inflammatory disorders. Hence, this study seeks to determine the antioxidant, anti-inflammatory and anti-arthritic activities of acetone leaf extracts of nine South African medicinal plants that have been used traditionally to treat arthritis and inflammation. METHODS: The anti-inflammatory activity of the extracts was determined by investigating inhibition of nitric oxide production in lipopolysaccharide activated RAW 264.7 macrophages as well as 15 lipoxygenase enzyme inhibition. An anti-protein denaturation assay was used to determine the anti-arthritic properties of the extracts. The antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3 ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power (FRAP). The total phenolic and total flavonoid concentration of extracts were determined by using standard methods. RESULTS: All extracts inhibited nitric oxide production in a dose-dependent manner in the LPS stimulated RAW 264.7 macrophages. Extracts of Maesa lanceolata and Heteromorpha arborescens inhibited NO production by 99.16 % and 89.48 % at a concentration of 30 MUg/ml respectively. Elaeodendron croceum and Calpurnia aurea extracts had strong activity against 15-lipoxygenase activity with IC50 values of 26.23 and 34.70 MUg/ml respectively. Morus mesozygia and Heteromorpha arborescens extracts had good in vitro anti-arthritic activity with IC50 values of 11.89 and 53.78 MUg/ml, the positive control diclofenac sodium had IC50 value of 32.37 MUg/ml. The free radical scavenging activity of the extracts in DPPH assays ranged between 7.72 and 154.77 MUg/ml. Trolox equivalent antioxidant capacity (TEAC) and FRAP values ranged from 0.06 to 1.32 and 0.06 to 0.99 respectively. CONCLUSIONS: Results from this study support the traditional use of the selected medicinal plants in the management of arthritis and other inflammatory conditions. The free radical scavenging capacity of the extracts may be related to an immune boosting potential. PMID- 27554101 TI - Antibiotic use and clinical outcomes in the acute setting under management by an infectious diseases acute physician versus other clinical teams: a cohort study. AB - OBJECTIVES: To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery. DESIGN: Prospective cohort study (1 week) and analysis of linked electronic health records (3 years). SETTING: UK tertiary care centre. PARTICIPANTS: All patients admitted sequentially to the acute medical service under an infectious diseases acute physician (IDP) and other medical teams during 1 week in 2013 (n=297), and 3 years 2012-2014 (n=47 585). PRIMARY OUTCOME MEASURE: Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case mix. SECONDARY OUTCOME MEASURES: 30-day all-cause mortality, treatment failure and length of stay. RESULTS: Antibiotic use was 173 vs 282 DOT/100 admissions in the IDP versus non-IDP group. Using case mix-adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07 to 0.84), p=0.03) and received shorter courses (adjusted rate ratio (RR)=0.71 (95% CI 0.54 to 0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% vs 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p>0.5; also in the 3-year data set), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24 to 10.03), p=0.03) and have longer length of stay (adjusted RR=1.19 (95% CI 1.05 to 1.36), p=0.007). CONCLUSIONS: The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will increase or decrease risk of antibiotic-resistant infections. PMID- 27554103 TI - Consent and widespread access to personal health information for the delivery of care: a large scale telephone survey of consumers' attitudes using vignettes in New Zealand. AB - OBJECTIVES: In light of recent health policy, to examine factors which influence the public's willingness to consent to share their health information in a national electronic health record (EHR). DESIGN: Data were collected in a national telephone survey in 2008. Respondents were presented with vignettes that described situations in which their health information was shared and asked if they would consent to such sharing. The subset, consisting of the 18 vignettes that covered proving care, was reanalysed in depth using new statistical methods in 2016. SETTING: Adult population of New Zealand accessible by telephone landline. PARTICIPANTS: 4209 adults aged 18+ years in the full data set, 2438 of which are included in the selected subset. MAIN OUTCOME MEASURES: For each of 18 vignettes, we measured the percentage of respondents who would consent for their information to be shared for 2 groups; for those who did not consider that their records contained sensitive information, and for those who did or refused to say. RESULTS: Rates of consent ranged from 89% (95% CI 87% to 92%) for sharing of information with hospital doctors and nurses to 51% (47% to 55%) for government agencies. Mixed-effects logistic regression was used to identify factors which had significant impact on consent. The role of the recipient and the level of detail influenced respondents' willingness to consent (p<0.0001 for both factors). Of the individual characteristics, the biggest impact was that respondents whose records contain sensitive information (or who refused to answer) were less willing to consent (p<0.0001). CONCLUSIONS: A proportion of the population are reluctant to share their health information beyond doctors, nurses and paramedics, particularly when records contain sensitive information. These findings may have adverse implications for healthcare strategies based on widespread sharing of information. Further research is needed to understand and overcome peoples' ambivalence towards sharing their information. PMID- 27554102 TI - African Breast Cancer-Disparities in Outcomes (ABC-DO): protocol of a multicountry mobile health prospective study of breast cancer survival in sub Saharan Africa. AB - INTRODUCTION: Sub-Saharan African (SSA) women with breast cancer (BC) have low survival rates from this potentially treatable disease. An understanding of context-specific societal, health-systems and woman-level barriers to BC early detection, diagnosis and treatment are needed. METHODS: The African Breast Cancer Disparities in Outcomes (ABC-DO) is a prospective hospital-based study of overall survival, impact on quality of life (QOL) and delays along the journey to diagnosis and treatment of BC in SSA. ABC-DO is currently recruiting in Namibia, Nigeria, South Africa, Uganda and Zambia. Women aged 18 years or older who present at participating secondary and tertiary hospitals with a new clinical or histocytological diagnosis of primary BC are invited to participate. For consented women, tumour characteristics, specimen and treatment data are obtained. Over a 2-year enrolment period, we aim to recruit 2000 women who, in the first instance, will be followed for between 1 and 3 years. A face-to-face baseline interview obtains information on socioeconomic, cultural and demographic factors, QOL, health and BC attitudes/knowledge, and timing of all prediagnostic contacts with caregivers in orthodox health, traditional and spiritual systems. Responses are immediately captured on mobile devices that are fed into a tailored mobile health (mHealth) study management system. This system implements the study protocol, by prompting study researchers to phone women on her mobile phone every 3 months and, failing to reach her, prompts contact with her next-of-kin. At follow-up calls, women provide updated information on QOL, care received and disease impacts on family and working life; date of death is asked of her next-of kin when relevant. ETHICS AND DISSEMINATION: The study was approved by ethics committees of all involved institutions. All participants provide written informed consent. The findings from the study will be published in peer-reviewed scientific journals, presented to funders and relevant local organisations and at scientific conferences. PMID- 27554104 TI - Prevalence and incidence of pulmonary hypertension among HIV-infected people in Africa: a systematic review and meta-analysis. AB - OBJECTIVE: Patients infected with HIV have a direly increased risk of developing pulmonary hypertension (PH), and of dying from the condition. While Africa carries the greatest burden of HIV infection worldwide, there is unclear data summarising the epidemiology of PH among HIV-infected people in this region. Our objective was to determine the prevalence and incidence of PH among HIV-infected people living across Africa. DESIGN: A systematic review and meta-analysis. PARTICIPANTS: HIV-infected African people residing in Africa. OUTCOME: Prevalence and incidence of PH diagnosed through echocardiography or right heart catheterisation. DATA SOURCES: Articles published in PubMed/MEDLINE, EMBASE, African Journals Online and African Index Medicus between 1 January 1980 and 30 June 2016, without any language restriction. RESULTS: Overall, 121 studies were screened; 3 were included in this review: 1 from Southern Africa (South Africa), 1 from Eastern Africa (Tanzania) and 1 from Central Africa (Cameroon). These studies included HIV-infected adult patients selected based on presentation with cardiovascular symptoms. No study reported PH incidence or PH incidence/prevalence among children and adolescents. The quality assessment yielded moderate risk of bias. Ages of participants ranged between 18 and 78 years, and the proportion of females varied between 52.3% and 68.8%. The prevalence of PH in the pooled sample of 664 patients was 14% (95% CI 6%-23%). LIMITATIONS: Only 3 studies were found eligible from 3 regions of the African continent. CONCLUSIONS: The prevalence of PH among HIV-infected people in Africa seems very high. Further studies are urgently warranted to determine the incidence of HIV-induced PH, which must include all subregions of Africa. TRIAL REGISTRATION NUMBER: Review registration number PROSPERO CRD42016033863. PMID- 27554106 TI - Association between hyperglycaemic crisis and long-term major adverse cardiovascular events: a nationwide population-based, propensity score-matched, cohort study. AB - OBJECTIVE: Hyperglycaemic crisis was associated with significant intrahospital morbidity and mortality. However, the association between hyperglycaemic crisis and long-term cardiovascular outcomes remained unknown. This study aimed to investigate the association between hyperglycaemic crisis and subsequent long term major adverse cardiovascular events (MACEs). PARTICIPANTS AND METHODS: This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database for the period of 1996-2012. A total of 2171 diabetic patients with hyperglycaemic crisis fit the inclusion criteria. Propensity score matching was used to match the baseline characteristics of the study cohort to construct a comparison cohort which comprised 8684 diabetic patients without hyperglycaemic crisis. The risk of long-term MACEs was compared between the two cohorts. RESULTS: Six hundred and seventy-six MACEs occurred in the study cohort and the event rate was higher than that in the comparison cohort (31.1% vs 24.1%, p<0.001). Patients with hyperglycaemic crisis were associated with a higher risk of long-term MACEs even after adjusting for all baseline characteristics and medications (adjusted HR=1.76, 95% CI 1.62 to 1.92, p<0.001). Acute myocardial infarction had the highest adjusted HR (adjusted HR=2.19, 95% CI 1.75 to 2.75, p<0.001) in the four types of MACEs, followed by congestive heart failure (adjusted HR=1.97, 95% CI 1.70 to 2.28, p<0.001). Younger patients with hyperglycaemic crisis had a higher risk of MACEs than older patients (adjusted HR=2.69 for patients aged 20-39 years vs adjusted HR=1.58 for patients aged >65 years). CONCLUSIONS: Hyperglycaemic crisis was significantly associated with long term MACEs, especially in the young population. Further prospective longitudinal study should be conducted for validation. PMID- 27554105 TI - Study to Improve Cardiovascular Outcomes in high-risk older patieNts (ICON1) with acute coronary syndrome: study design and protocol of a prospective observational study. AB - INTRODUCTION: The ICON1 study (a study to Improve Cardiovascular Outcomes in high risk older patieNts with acute coronary syndrome) is a prospective observational study of older patients (>=75 years old) with non-ST-elevation acute coronary syndrome managed by contemporary treatment (pharmacological and invasive). The aim of the study was to determine the predictors of poor cardiovascular outcomes in this age group and to generate a risk prediction tool. METHODS AND ANALYSIS: Participants are recruited from 2 tertiary hospitals in the UK. Baseline evaluation includes frailty, comorbidity, cognition and quality-of-life measures, inflammatory status assessed by a biomarker panel, including microRNAs, senescence assessed by telomere length and telomerase activity, cardiovascular status assessed by arterial stiffness, endothelial function, carotid intima media thickness and left ventricular systolic and diastolic function, and coronary plaque assessed by virtual histology intravascular ultrasound and optical coherence tomography. The patients are followed-up at 30 days and at 1 year for primary outcome measures of death, myocardial infarction, stroke, unplanned revascularisation, bleeding and rehospitalisation. ETHICS AND DISSEMINATION: The study has been approved by the regional ethics committee (REC 12/NE/016). Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT01933581: Pre results. PMID- 27554107 TI - Maternal morbidity and mortality from severe sepsis: a national cohort study. AB - OBJECTIVES: To describe the incidence, characteristics and risk factors for critical care admission with severe maternal sepsis in the UK. DESIGN: National cohort study. SETTING: 198 critical care units in the UK. PARTICIPANTS: 646 pregnant and recently pregnant women who had severe sepsis within the first 24 hours of admission in 2008-2010. PRIMARY AND SECONDARY OUTCOME MEASURES: Septic shock, mortality. RESULTS: Of all maternal critical care admissions, 14.4% (n=646) had severe sepsis; 10.6% (n=474) had septic shock. The absolute risk of maternal critical care admission with severe sepsis was 4.1/10 000 maternities. Pneumonia/respiratory infection (irrespective of the H1N1 pandemic influenza strain) and genital tract infection were the most common sources of sepsis (40% and 24%, respectively). We identified a significant gradient in the risk of severe maternal sepsis associated with increasing deprivation (RR=6.5; 95% CI 4.9 to 8.5 most deprived compared with most affluent women). The absolute risk of mortality was 1.8/100 000 maternities. The most common source of infection among women who died was pneumonia/respiratory infection (41%). Known risk factors for morbidity supported by this study were: younger age, multiple gestation birth and caesarean section. Significant risk factors for mortality in unadjusted analysis were: age >=35 years (unadjusted OR (uOR)=3.5; 95% CI 1.1 to 10.6), >=3 organ system dysfunctions (uOR=12.7; 95% CI 2.9 to 55.1), respiratory dysfunction (uOR=6.5; 95% CI1.9 to 21.6), renal dysfunction (uOR=5.6; 95% CI 2.3 to 13.4) and haematological dysfunction (uOR=6.5; 95% CI 2.9 to 14.6). CONCLUSIONS: This study suggests a need to improve timely recognition of severe respiratory tract and genital tract infection in the obstetric population. The social gradient associated with the risk of severe sepsis morbidity and mortality raises important questions regarding maternal health service provision and usage. PMID- 27554110 TI - Social Science-Environmental Health Collaborations: An Exciting New Direction. AB - The Social Science-Environmental Health Collaborations Conference in May 2016 was a unique gathering of scholars from the social sciences and environmental health sciences, government agency professionals, community organizers and activists, and students. Conference participants described the research and practice of environmental public health as done through a transdisciplinary lens and with a community-based participatory research/community-engaged research model. NIEHS' role in supporting such work has helped create a growing number of social and environmental health scientists who cross boundaries as they work with each other and with community-based organizations. PMID- 27554108 TI - Thyroid hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis. AB - Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases. PMID- 27554111 TI - C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis. AB - C-peptide exerts protective effects against diabetic complications; however, its role in inhibiting hyperglycemic memory (HGM) has not been elucidated. We investigated the beneficial effect of C-peptide on HGM-induced vascular damage in vitro and in vivo using human umbilical vein endothelial cells and diabetic mice. HGM induced apoptosis by persistent generation of intracellular ROS and sustained formation of ONOO(-) and nitrotyrosine. These HGM-induced intracellular events were normalized by treatment with C-peptide, but not insulin, in endothelial cells. C-peptide also inhibited persistent upregulation of p53 and activation of mitochondrial adaptor p66(shc) after glucose normalization. Further, C-peptide replacement therapy prevented persistent generation of ROS and ONOO(-) in the aorta of diabetic mice whose glucose levels were normalized by the administration of insulin. C-peptide, but not insulin, also prevented HGM-induced endothelial apoptosis in the murine diabetic aorta. This study highlights a promising role for C-peptide in preventing HGM-induced intracellular events and diabetic vascular damage. PMID- 27554116 TI - C-reactive Protein Level, Apolipoprotein B-to-apolipoprotein A-1 Ratio, and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China. AB - OBJECTIVE: We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1 (ApoB/ApoA-1) ratio on the incidence of ischemic stroke (IS) or coronary heart disease (CHD) in a Mongolian population in China. METHODS: From June 2003 to July 2012, 2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation. All the participants were divided into four subgroups according to C-reactive protein (CRP) level and ApoB/ApoA-1 ratio. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the IS and CHD events in all the subgroups. RESULTS: The HRs (95% CI) for IS and CHD were 1.33 (0.84-2.12), 1.14 (0.69-1.88), and 1.91 (1.17-3.11) in the 'low CRP level with high ApoB/ApoA-1', 'high CRP level with low ApoB/ApoA-1', and 'high CRP level with high ApoB/ApoA-1' subgroups, respectively, in comparison with the 'low CRP level with low ApoB/ApoA-1' subgroup. The risks of IS and CHD events was highest in the 'high CRP level with high ApoB/ApoA-1' subgroup, with statistical significance. CONCLUSION: High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population. This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population. PMID- 27554109 TI - Adipokines in psoriasis: An important link between skin inflammation and metabolic alterations. AB - Psoriasis is a chronic inflammatory skin disease most common in Europe, North America, and Australia. The etiology and pathomechanisms underlying the evolution and persistence of the skin alterations are increasingly being understood and have led to the development of effective anti-psoriatic therapies. Apart from the skin manifestations, psoriasis is associated with the metabolic syndrome (MetS), known to increase the risk of type 2 diabetes mellitus and cardiovascular disorders. Research of the last years demonstrated a dysregulated adipokine balance as an important link between inflammation, MetS, and consequential disorders. This article describes selected adipokines and their potential role in both metabolic comorbidity and skin inflammation in psoriasis. PMID- 27554117 TI - Ideal Cardiovascular Health Metrics and Coronary Artery Calcification in Northern Chinese Population: A Cross-sectional Study. AB - OBJECTIVE: Coronary artery calcification (CAC) is a well-established risk predictor of coronary heart disease events and is recognized as an indicator of subclinical atherosclerosis. METHODS: A cross-sectional study consisting of 2999 participants aged ?40 years from the Jidong community of Tangshan City, an industrial and modern city of China, was conducted between 2013 and 2014 to examine the association between the ideal cardiovascular health (CVH) metrics and CAC. The ideal CVH metrics were determined based on the definition of the American Heart Association (AHA). The participants were then grouped into 4 categories according to the quartiles of their CVH metric scores as follows: first quartile (0-2), second quartile (3), third quartile (4), and fourth quartile (5-7). CAC was assessed by using high-pitch dual-source CT, and patients were identified based on thresholds of 0, 10, 100, or 400 Agatston units, as per common practice. RESULTS: The prevalence of subclinical atherosclerosis was 15.92%, 13.85%, 6.76%, and 1.93%, determined by using the CAC scores at thresholds of 0, 10, 100, and 400 Agatston units, respectively. Compared with the group in the first quartile, the other three CVH groups had a lower odds ratio of CAC >0 after adjusting for age, sex, income level, education level, and alcohol use in the logistic regression analysis. The odds ratios in these groups were 0.86 [95% confidence interval (CI), 0.63-1.17; P<0.05], 0.75 (95% CI, 0.55-1.02; P<0.05), and 0.49 (95% CI, 0.35-0.69; P<0.05), respectively. These associations of CAC with the CVH metrics were consistent when different CAC cutoff scores were used (0, 10, 100, or 400). CONCLUSION: The participants with more-ideal cardiovascular metrics had a lower prevalence of subclinical atherosclerosis determined according to CAC score. Maintaining an ideal cardiovascular health may be valuable in the prevention of atherosclerosis in the general population. PMID- 27554118 TI - p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis. AB - OBJECTIVE: To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. METHODS: Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-beta galactosidase (SA-beta-gal) staining combined with Ki67 staining, a cell proliferation marker. RESULTS: Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. CONCLUSION: Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2 arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis. PMID- 27554119 TI - Autophagy Attenuates MnCl2-induced Apoptosis in Human Bronchial Epithelial Cells. AB - OBJECTIVE: To investigate the role of autophagy in MnCl2-induced apoptosis in human bronchial epithelial 16HBE cells. METHODS: Cell proliferation was measured by MTT assay. Mitochondrial membrane potential (MMP) and apoptosis were measured by flow cytometry. Autophagic vacuoles were detected by fluorescence microscopy. Cellular levels of apoptosis and autophagy-related proteins were measured by western blotting. RESULTS: 16HBE cell proliferation was inhibited by MnCl2 in a dose- and time-dependent manner. MnCl2-induced 16HBE cell growth inhibition was related to MMP depolarization prior to the induction of apoptosis. Our data revealed that MnCl2-induced apoptosis in 16HBE cells was mediated by decreased expression of Bcl-2 and increased levels of cleaved caspase-3. It was observed that when we exposed 16HBE cells to MnCl2 in a dose-dependent manner, the formation of autophagic vacuoles and the levels of LC-3B-II were elevated. RNA interference of LC3B in these MnCl2-exposed cells demonstrated that MMP loss and apoptosis were enhanced. Additionally, the pan-caspase inhibitor Z-VAD-FMK increased the cellular levels of Bcl-2 and decreased apoptosis, but did not affect the cellular levels of LC3B in MnCl2-treated 16HBE cells. CONCLUSION: MnCl2 dose- and time-dependently inhibits 16HBE cell proliferation and induces MMP loss and apoptosis. Autophagy acts in a protective role against MnCl2-induced apoptosis in 16HBE cells. PMID- 27554120 TI - Association of the ADIPOQ Rs2241766 and Rs266729 Polymorphisms with Metabolic Syndrome in the Chinese Population: A Meta-analysis. AB - OBJECTIVE: This meta-analysis was performed to summarize the association of the ADIPOQ rs2241766 and rs266729 polymorphisms with metabolic syndrome (MS) in the Chinese population. METHODS: We searched for articles in MEDLINE via PubMed, EMBASE, HuGE Navigator, CNKI, and Wanfang databases and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to determine the strength of associations in fixed- or random-effects models. RESULTS: We included 21 articles in the meta-analysis: 17 reports of ADIPOQ rs2241766 with 3628 cases and 3000 controls and 8 of rs266729 with 2021 cases and 2226 controls. We found an increased risk of MS with the ADIPOQ rs2241766 polymorphism in some genetic models (allele model: OR=1.12, 95% CI: 1.03-1.21; dominant model: OR=1.15, 95% CI: 1.04-1.28; homozygote model: OR=1.22, 95% CI: 1.00-1.49) but no association with the ADIPOQ rs266729 polymorphism (allele model: OR=0.98, 95% CI: 0.82-1.17; dominant model: OR=0.90, 95% CI: 0.79-1.02; recessive model: OR=1.09, 95% CI: 0.85-1.39; homozygote model: OR=1.03, 95% CI: 0.80-1.33). CONCLUSION: The results of this meta-analysis suggest an association between the ADIPOQ rs2241766 polymorphism and MS in the Chinese population. G allele of ADIPOQ rs2241766 increases the risk of MS. Better designed studies with different ethnic populations and larger sample sizes are needed for assessing the relationship between ADIPOQ rs2241766 and rs266729 polymorphisms and MS in the future. PMID- 27554121 TI - Lack of Association between rs4331426 Polymorphism in the Chr18q11.2 Locus and Pulmonary Tuberculosis in an Iranian Population. AB - OBJECTIVE: The effect of rs4331426 polymorphism in the Chr18q11.2 locus on pulmonary tuberculosis (PTB) risk was evaluated. METHODS: This case-control study included 208 PTB patients and 204 healthy subjects. Genotyping of the rs4331426 variant was conducted using polymerase chain reaction restriction fragment length polymorphism. RESULTS: The frequencies of genotypes AA, AG, and GG polymorphisms were 83.1%, 15.9%, and 1.0% in the PTB group and 84.3%, 15.2%, and 0.5% in the control group, respectively. The frequency of the minor (G) allele was 8.9% in the PTB group and 8.1% in controls. Neither genotype nor allele frequencies of the rs4331426 variant showed statistically significant differences between PTB and controls. In addition, stratification by sex showed no significant association between the rs4331426 variant and PTB risk in males or females. CONCLUSION: In conclusion, the results of this study do not support an association between the rs4331426 polymorphism and risk of PTB in an Iranian population. PMID- 27554122 TI - Detection of Multi-drug Resistant Acinetobacter Lwoffii Isolated from Soil of Mink Farm. AB - There were 4 Acinetobacter lwoffii obtained from soil samples. The antimicrobial susceptibility of the strains to 16 antimicrobial agents was investigated using K B method. Three isolates showed the multi-drug resistance. The presence of resistance genes and integrons was determined using PCR. The aadA1, aac(3')-IIc, aph(3')-VII, aac(6')-Ib, sul2, cat2, floR, and tet(K) genes were detected, respectively. Three class 1 integrons were obtained. The arr-3-aacA4 and blaPSE-1 gene cassette, which cause resistance to aminoglycoside and beta-lactamase antibiotics. Our results reported the detection of multi-drug resistant and carried resistant genes Acinetobacter lwoffii from soil. The findings suggested that we should pay close attention to the prevalence of multi-drug resistant bacterial species of environment. PMID- 27554123 TI - Green Tea Polyphenols Alleviate Autophagy Inhibition Induced by High Glucose in Endothelial Cells. AB - Bovine aortic endothelial cells (BAECs) were cultured with high glucose (33 mmol/L), 4 mg/L green tea polyphenols (GTPs) or 4 mg/L GTPs co-treatment with high glucose for 24 h in the presence or absence of Bafilomycin-A1 (BAF). We observed that high glucose increased the accumulation of LC3-II. Treatment with BAF did not further increase the accumulation of LC3-II. Results also showed an increased level of p62 and decreased Beclin-1. However, GTPs showed inversed trends of those proteins. Furthermore, GTPs co-treatment with high glucose decreased the level of LC3-II and a much higher accumulation of LC3-II was observed in the presence of BAF in comparison with high glucose alone. Results also showed a decreased p62 and increased Beclin-1. The results demonstrated that GTPs alleviated autophagy inhibition induced by high glucose, which may be involved in the endothelial protective effects of green tea against hyperglycemia. PMID- 27554124 TI - Cytotoxic Responses and Apoptosis in Rat Kidney Epithelial Cells Exposed to Lead. AB - The toxic effects of lead on normal rat kidney epithelial cells (NRK cells) may occur via various pathways. However, the role of intrinsic mitochondrial pathway in Lead-induced apoptosis in NRK cells has not been investigated. The purpose of our study was to investigate cytotoxic responses and cell apoptosis mediated by lead in NRK cells. NRK cells were treated with different concentrations of Lead acetate for 12 h to determine the cytotoxicity of lead. Mitochondrial transmembrane potential was also analyzed using a fluorescence spectrophotometer. Moreover, the activities of caspase-3 and caspase-9 were detected in the presence of lead. Finally, the lead-induced cell apoptosis was evaluated by flow cytometry in the present of caspase inhibitors Z-VAD-FMK and Ac-LEHD-FMK, respectively. The results would contribute to clarify the role of Lead in proliferation and apoptosis of NRK cells, and help to understand the underlying mechanism responsible for lead-induced cell apoptosis. PMID- 27554125 TI - Prevalence of High Non-high-density Lipoprotein Cholesterol and Associated Risk Factors in Patients with Diabetes Mellitus in Jilin Province, China: A Cross sectional Study. AB - Dyslipidemia is a risk factor for cardiovascular diseases (CVDs) in patients with diabetes, and non-high-density lipoprotein cholesterol (non-HDL-C) is a better predictor of CVDs than low-density lipoprotein cholesterol (LDL-C) in patients with diabetes. Therefore, we aimed to investigate the distribution of non-HDL-C and the prevalence of high non-HDL-C level in Chinese patients with diabetes mellitus and identify the associated risk factors. Non-HDL-C concentration positively correlated with total cholesterol, triglycerides, and LDL-C concentrations. Although both non-HDL-C and LDL-C concentration both related positively with TC concentration, the magnitude of correlation was relatively higher for non-HDL-C. The prevalence of high non-HDL-C (?4.14 mmol/L) was higher in two age groups (55-64 years: 46.7%; 65-79 years: 47.3%) than other age groups (18-24 years: 4.2%; 25-34 years: 43.6%; 35-44 years: 38.1%; 45-54 years: 41.0%). It was also higher among overweight (45.1%), generally obese (50.9%), or abdominally obese (47.3%) subjects, compared with normal weight subjects (34.5%). The risk of high non-HDL-C increased with advancing age. Both general obesity [odds ratio (OR)=1.488, 95% confidence interval (CI): 1.003-2.209] and abdominal obesity (OR=1.561, 95% CI: 1.101-2.214) were significantly associated with high non-HDL-C levels. PMID- 27554126 TI - Exploring Genome-wide DNA Methylation Profiles Altered in Kashin-Beck Disease Using Infinium Human Methylation 450 Bead Chips. AB - To understand how differentially methylated genes (DMGs) might affect the pathogenesis of Kashin-Beck disease (KBD). Genome-wide methylation profiling of whole blood from 12 matched KBD and controls pairs was performed using a high resolution Infinium 450 K methylation array. In total, 97 CpG sites were differentially methylated in KBD compared to the normal controls; of these sites, 36 sites were significantly hypermethylated (covering 22 genes) and 61 sites were significantly hypomethylated (covering 34 genes). Of these genes, 14 significant pathways were identified, the most significant P value pathway was type I diabetes mellitus pathway and pathways associated with autoimmune diseases and inflammatory diseases were included in this study. Subsequently, 4 CpG sites in HLA-DRB1 were validated using bisulfite sequencing polymerase chain reaction (BSP) in articular cartilage, and the results showed significant differences in the methylation status between KBD and controls, consistent with the results of the high-resolution array. These results suggested that differences in genome wide DNA methylation exist between KBD and the controls, and the biological pathways support the autoimmune disease and inflammatory disease hypothesis of KBD. PMID- 27554128 TI - Density functional theory: a tale of success in three codes. PMID- 27554127 TI - Direct Cardiac Cellular Reprogramming for Cardiac Regeneration. AB - OPINION STATEMENT: Direct cardiac cellular reprogramming of endogenous cardiac fibroblasts directly into induced cardiomyocytes is a highly feasible, promising therapeutic option for patients with advanced heart failure. The most successful cardiac reprogramming strategy will likely be a multimodal approach involving an optimal combination of cardio-differentiating factors, suppression of fibroblast gene expression, and induction of angiogenic factors. PMID- 27554129 TI - Editorial (Thematic Issue: Development of Biomarkers in Tumors of Digestive System Part II). PMID- 27554130 TI - Rhodium(III)-Catalyzed Regio- and Stereoselective C-H Allylation of Arenes with Vinyl Benzoxazinanones. AB - Vinyl benzoxazinanone was applied as an electrophilic allylating reagent for a series of arenes under redox-neutral Rh(III) catalysis. This reaction occurs in high efficiency under mild conditions to afford allylarenes bearing a sulfonamide functionality in exclusively E-selectivity. This allylation system combines C-H activation of arenes and scission of an unstrained six-membered ring. PMID- 27554131 TI - Gene polymorphisms as a predictor of body weight loss after Roux-en-Y gastric bypass surgery among obese women. AB - This study aimed to investigate the association between twelve gene polymorphisms and body weight loss, 12 months after Roux-en-Y gastric bypass (RYGB) surgery. Three hundred and fifty-one obese women participated in this study. The statistical software WEKA was used to identify which gene polymorphisms were potential predictors of postoperative percentage of excess weight loss (%EWL). Our results indicate that the only gene polymorphism that predicted %EWL was rs3813929, which is related to the serotonin receptor gene (5-HT2C). Therefore, the 5-HT2C gene polymorphism rs3813929 (more specifically, the TT genotype) predicted greater %EWL 12 months after RYGB surgery among female patients. PMID- 27554132 TI - Relationship between serum betatrophin levels and the first-phase of glucose stimulated insulin secretion. AB - AIMS: To examine circulating betatrophin concentrations in subjects with different glucose tolerance status and to investigate the relationship between serum betatrophin levels and first-phase of glucose-stimulated insulin secretion. METHODS: Serum betatrophin concentrations were measured in 110 age- and sex matched subjects: 47 newly diagnosed type 2 diabetes mellitus (T2DM), 29 impaired glucose tolerance (IGT) and 34 normal glucose tolerance (NGT). Oral glucose tolerance test and intravenous glucose tolerance test were performed to assess glucose tolerance and first-phase of glucose-stimulated insulin secretion. RESULTS: Serum betatrophin levels were significantly higher in the T2DM and IGT group than in the NGT group (2.10+/-1.16ng/mL vs 0.77+/-0.44ng/mL, 1.73+/ 1.28ng/mL vs 0.77+/-0.44ng/mL; P<0.01). The AIR and AUC among the three groups showed a progressive decrease from the NGT to IGT group with the lowest value in the T2DM group (P<0.01). Betatrophin were found to be positively correlated with BMI, waist circumference (WC), homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), and inversely associated with HDL-c (all P<0.01), but not significantly correlated with 0-10min insulin the area under the curve (AUC) and acute insulin response (AIR) (P>0.05). Stepwise multiple regression analysis showed that HOMA-IR and TG were independently related to betatrophin (P<0.05). CONCLUSION: Serum betatrophin concentrations were higher in T2DM and IGT, and were closely related to glucolipid disorder, insulin resistance, but not related to the first-phase of glucose-stimulated insulin secretion. PMID- 27554133 TI - Effect of texture of platelet bags on bacterial and platelet adhesion. AB - BACKGROUND: Missed detection of Staphylococcus epidermidis contamination in platelet (PLT) storage bags by the standard 24-hour-postcollection BacT/ALERT screening test has been documented. A slow growth rate and the strong tendency of this bacterium to adhere to surfaces can contribute to missed detection of the pathogen. STUDY DESIGN AND METHODS: Topography of two different PLT storage bag surfaces, textured (rough) and smooth surfaces of Terumo 80440 bags (designated A15), was studied. Adhesion of biofilm-positive and -negative S. epidermidis strains on these surfaces was evaluated under static conditions. Quality of stored PLTs in A15 bags under blood bank conditions was compared for two different bag orientations (rough vs. smooth surface down) on Days 2, 5, and 7 of storage. PLT adhesion on the surfaces was evaluated after 7 days of storage. RESULTS: Bacterial adhesion and biofilm formation were significantly higher on the rough surfaces of A15 bags compared to the smooth surfaces. After 7 days of storage in A15 bags, PLTs showed similar metabolite levels, pH, and response capacity in the bags with different orientation and more PLT adhesion and aggregation was observed on rough surfaces. CONCLUSION: Higher bacterial adhesion on rough surfaces can contribute to missed detection of bacterial strains that tend to adhere on surfaces. PLT adhesion and aggregation on rough surfaces can affect the quality and safety of PLTs by promoting more bacterial adhesion and biofilm formation on surfaces. PMID- 27554135 TI - Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder. AB - Individuals with autism spectrum disorders (ASD) have impaired detoxification capacity. Investigating the neurobiological bases of impaired antioxidant capacity is thus a research priority in the pathophysiology of ASD. We measured the urinary levels of hexanoyl-lysine (HEL) which is a new oxidative stress biomarker, total antioxidant power (TAP) and DNA methylation biomarker 8-hydroxy 2'-deoxyguanosine (8-OHdG), and the plasma levels of superoxide dismutase (SOD), which is a major antioxidant enzyme. We examined whether the urinary levels of these enzymes and biomarkers may be related to symptoms of social impairment in 20 individuals with ASD (meanage,11.1+/-5.2years) and 12 age- and gender-matched healthy controls (meanage,14.3+/-6.2years). Symptoms of social impairment were assessed using the Social Responsiveness Scale (SRS). The dietary TAP of the fruit juice, chocolate, cookies, biscuits, jam and marmalade were significantly higher in the ASD group than in the control group, although the intake of nutrients was not significantly different between the groups. The urinary TAP levels were significantly lower in the ASD group than in the control group. There were no significantly differences in urinary HEL and 8-OHdG levels between the ASD and control groups. The SRS scores were significantly higher in the ASD group than in the control group. Stepwise regression analysis revealed that urinary TAP levels and plasma SOD levels can differences in the biomarkers and the SRS scores between the ASD group and the control group. The endogenous antioxidant capacity may be deficient without altered urinary HEL and 8-OHdG levels in individuals with ASD. The plasma SOD levels may be related to reduced endogenous antioxidant capacity. PMID- 27554134 TI - Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT). AB - BACKGROUND AND AIMS: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT). METHODS: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT. RESULTS: Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin<35g/L was independently associated with severe infection. Compared with baseline values, a significant decrease (P=0.02) of the physical dimension of health-related quality of life was observed between W4 and W24. The mean (95% CI) number of self-reported symptoms doubled during treatment (from 6.3 [4.8-7.7] to 11.8 [9.3-14.3]; P<0.001). CONCLUSIONS: The safety of the PEG-IFN/RBV/boceprevir combination is poor in patients awaiting LT, with a high risk of severe infection. Moreover, the limited efficacy confirms the indication for IFN-free combinations in these patients. PMID- 27554136 TI - Smyd3-associated regulatory pathways in cancer. AB - SMYD3 is a member of the SET and MYND-domain family of methyl-transferases, the increased expression of which correlates with poor prognosis in various types of cancer. In liver and colon tumors, SMYD3 is localized in the nucleus, where it interacts with RNA Pol II and H3K4me3 and functions as a selective transcriptional amplifier of oncogenes and genes that control cell proliferation and metastatic spread. Smyd3 expression has a high discriminative power for the characterization of liver tumors and positively correlates with poor prognosis. In lung and pancreatic cancer, SMYD3 acts in the cytoplasm, potentiating oncogenic Ras/ERK signaling through the methylation of the MAP3K2 kinase and the subsequent release from its inhibitor. A clinico-pathological analysis of lung cancer patients uncovers prognostic significance of SMYD3 only for first progression survival. However, stratification of patients according to their smoking history significantly expands the prognostic value of SMYD3 to overall survival and other features, suggesting that smoking-related effects saturate the clinical analysis and mask the function of SMYD3 as an oncogenic potentiator. PMID- 27554137 TI - Graphene-based extremely wide-angle tunable metamaterial absorber. AB - We investigate the absorption properties of graphene-based anisotropic metamaterial structures where the metamaterial layer possesses an electromagnetic response corresponding to a near-zero permittivity. We find that through analytical and numerical studies, near perfect absorption arises over an unusually broad range of beam incidence angles. Due to the presence of graphene, the absorption is tunable via a gate voltage, providing dynamic control of the energy transmission. We show that this strongly enhanced absorption arises due to a coupling between light and a fast wave-mode propagating along the graphene/metamaterial hybrid. PMID- 27554138 TI - Enhanced Piezoelectric Response due to Polarization Rotation in Cobalt Substituted BiFeO3 Epitaxial Thin Films. AB - Polarization rotation induced by an external electric field in piezoelectric materials such as PbZr1-x Tix O3 is generally regarded as the origin of their large piezoelectric responses. Here, the piezoelectric responses of high-quality cobalt-substituted BiFeO3 epitaxial thin films with monoclinic distortions are systematically examined. It is demonstrated that polarization rotation plays a crucial role in improving the piezoelectric responses in this material. PMID- 27554139 TI - Assessment of quality of life in adolescent patients with cancer and adolescent survivors of childhood cancer. AB - PURPOSE: The aim of the study was to assess the quality of life (QoL) of adolescents with cancer and survivors of childhood cancer as well as the effect of various demographic factors upon it. DESIGN AND METHODS: The sample of the study included 82 adolescents aged 13-20 years who had been diagnosed with any type of cancer. Twenty-six of them received treatment and 56 survivors of childhood cancer had successfully completed their treatment. Data collection lasted from July 2010 to December 2012 in Children's Hematology-Oncology Unit in Athens. For data collection, Minneapolis-Manchester Quality Questionnaire of Life Instrument was used. The assessment of the QoL of adolescents undergoing treatment was performed with three measurements and that of the survivors with one. RESULTS: The QoL of adolescent patients did not significantly change during treatment and they showed a satisfactory QoL. Boys scored higher than girls (z = 1.78, p = .04 in psychological function and t = 2.27, p = .02 in body image) as far as QoL in social relations is concerned (z = -2.79, p = .002 in first measurement and z = -2.31, p = .01 in second measurement). Scores on the scale for the QoL of survivors of childhood cancer who completed treatment was 3.91. Survivors showed a higher QoL than the adolescent patients. CONCLUSIONS: This research has shown that the studied population scored a sufficient QoL, especially survivors of childhood cancer ones. Moreover, their QoL seemed to be influenced by the stage of treatment, the type of cancer, sex, age, family support, and their level of education. PMID- 27554140 TI - Biocide tolerance, phenotypic and molecular response of lactic acid bacteria isolated from naturally-fermented Alorena table to different physico-chemical stresses. AB - Lactic acid bacteria (LAB) isolated throughout the fermentation process of Alorena table olives were found to be resistant at least to three antibiotics (Casado Munoz et al., 2014); however, most were sensitive to the biocides tested in this study (with minimum inhibitory concentrations [MIC] below the epidemiological cut-off values). 2-15% of the isolates were found to be biocide resistant: Leuconostoc Pseudomesenteroides, which were resistant to hexachlorophene, and Lactobacillus pentosus to cetrimide and hexadecylpiridinium. We analyzed the effect of different physico-chemical stresses, including antimicrobials, on the phenotypic and genotypic responses of LAB, providing new insights on how they become resistant in a changing environment. Results indicated that similar phenotypic responses were obtained under three stress conditions: antimicrobials, chemicals and UV light. Susceptibility patterns to antibiotics changed: increasing MICs for ampicillin, chloramphenicol, ciprofloxacin, teicoplanin and tetracycline, and decreasing the MICs for clindamycin, erythromycin, streptomycin and trimethoprim in most strains. Statistically, cross resistance between different antibiotics was detected in all stress conditions. However, expression profiles of selected genes involved in stress/resistance response (rpsL, recA, uvrB and srtA) differed depending on the stress parameter, LAB species and strain, and the target gene. We conclude that, despite the uniform phenotypic response to stresses, the repertoire of induced and repressed genes differs. So, a search for a target to improve stress tolerance of LAB, especially those of importance as starter/protective cultures or probiotics, may depend on the individual screening of each strain, even though we could predict the antibiotic phenotypic response to all stresses. PMID- 27554141 TI - Modeling optimal process conditions for UV-heat inactivation of foodborne pathogens in liquid foods. AB - The combination of ultraviolet radiation and heat (UV-H treatment) has been demonstrated as a promising strategy to overcome the limited UV germicidal effect in fruit juices. Nonetheless, there are so far no data regarding the efficacy of the combined process for the inactivation of bacterial foodborne pathogens in other liquid foods with different pH and composition. In this investigation, the optimum UV-H processing conditions for the inactivation of Escherichia coli, Salmonella Typhimurium, Listeria monocytogenes, and S. aureus in chicken and vegetable broth, in addition to juices, were determined. From these data models that accurately predict the most advantageous UV-H treatment temperature and the expected synergistic lethal effect from UV and heat resistance data separately were constructed. Equations demonstrated that the optimum UV-H treatment temperature mostly depended on heat resistance, whereas the maximum synergistic lethal effect also was affected by the UV resistance of the microorganism of concern in a particular food. PMID- 27554142 TI - Genetically engineered Oenococcus oeni strains to highlight the impact of estA2 and estA7 esterase genes on wine ester profile. AB - Besides deacidifying wine, Oenococcus oeni bring significant changes in the chemical composition of wine by releasing esters by the action of their own esterases. The impact of O. oeni esterases remains relatively unexplored. Four esterase genes were identified from O. oeni genome (estA2, estA7, estC, and estB). The dual objective of this study was, first to use a genetic tool enabling the expression of esterase genes in enological conditions and, second, to investigate the impact of O. oeni esterase gene expression during winemaking on wine aromatic profile. Both estA2 and estA7 genes were successfully cloned and expressed in O. oeni and recombinant strains were inoculated in Aligote wine to initiate malolactic fermentation (MLF). Ester profile of experimental wine was established by SPME-GC-MS. EstA2 caused significant decreases in the concentrations of isoamyl acetate, ethyl hexanoate, isobutyl acetate, and hexyl acetate, by 42.7%, 23.4%, 51.5%, and 28.9%, respectively. EstA2 has preferential hydrolytic activity toward acetate esters from higher alcohols. EstA7 has synthetic activity toward hexyl acetate with a significant 22.7% increase. This study reports the first efficient expression system enabling the production of a functional protein in O. oeni in enological conditions. PMID- 27554143 TI - Selection of autochthonous lactic acid bacteria from goat dairies and their addition to evaluate the inhibition of Salmonella typhi in artisanal cheese. AB - This study aimed to select autochthonous lactic acid bacteria (LAB) with probiotic and functional properties from goat dairies and test their addition to artisanal cheese for the inhibition of Salmonella typhi. In vitro tests, including survival in the gastrointestinal tract (GIT), auto- and co-aggregation, the hemolytic test, DNase activity, antimicrobial susceptibility, antibacterial activity, tolerance to NaCl and exopolysaccharide (EPS), gas and diacetyl production were conducted for sixty isolates. Based on these tests, four LAB isolates (UNIVASF CAP 16, 45, 84 and 279) were selected and identified. Additional tests, such as production of lactic and citric acids by UNIVASF CAP isolates were performed in addition to assays of bile salt hydrolase (BSH), beta galactosidase and decarboxylase activity. The four selected LAB produced high lactic acid (>17 g/L) and low citric acid (0.2 g/L) concentrations. All selected strains showed BSH and beta-galactosidase activity and none showed decarboxylase activity. Three goat cheeses (1, 2 and control) were produced and evaluated for the inhibitory action of selected LAB against Salmonella typhi. The cheese inoculated with LAB (cheese 2) decreased 0.38 log10 CFU/g of S. Typhy population while in the cheese without LAB inoculation (cheese 1) the pathogen population increased by 0.29 log units. Further, the pH value increased linearly over time, by 0.004 units per day in cheese 1. In the cheese 2, the pH value decreased linearly over time, by 0.066 units per day. The cocktail containing selected Lactobacillus strains with potential probiotic and technological properties showed antibacterial activity against S. typhi in vitro and in artisanal goat cheese. Thus, goat milk is important source of potential probiotic LAB which may be used to inhibit the growth of Salmonella population in cheese goat, contributing to safety and functional value of the product. PMID- 27554144 TI - Potential transfer of extended spectrum beta-lactamase encoding gene, blashv18 gene, between Klebsiella pneumoniae in raw foods. AB - This study investigated the transfer frequency of the extended-spectrum beta lactamase-encoding gene (blaSHV18) among Klebsiella pneumoniae in tryptic soy broth (TSB), pasteurized milk, unpasteurized milk, alfalfa sprouts and chopped lettuce at defined temperatures. All transconjugants were characterized phenotypically and genotypically. KP04(DeltaKM) and KP08(DeltaKM) isolated from seed sprouts and KP342 were used as recipients in mating experiments with K. pneumoniae ATCC 700603 serving as the donor. In mating experiments, no transconjugants were detected at 4 degrees C in liquid media or chopped lettuce, but detected in all media tested at 15 degrees C, 24 degrees C, and 37 degrees C. At 24 degrees C, the transfer of blaSHV18 gene occurred more frequently in alfalfa sprouts (5.15E-04 transconjugants per recipient) and chopped lettuce (3.85E-05) than liquid media (1.08E-05). On chopped lettuce, transconjugants were not detected at day 1 post-mating at 15 degrees C, but observed on day 2 (1.43E 05). Transconjugants carried the blaSHV18 gene transferred from the donor and the virulence gene harbored by recipient. More importantly, a class 1 integrase gene and resistance to tetracycline, trimethoprim/sulfamethoxazole were co-transferred during mating. These quantitative results suggest that fresh produce exposed to temperature abuse may serve as a competent vehicle for the spread of gene encoding for antibiotic resistance, having a potential negative impact on human health. PMID- 27554145 TI - Do bacterial cell numbers follow a theoretical Poisson distribution? Comparison of experimentally obtained numbers of single cells with random number generation via computer simulation. AB - We investigated a bacterial sample preparation procedure for single-cell studies. In the present study, we examined whether single bacterial cells obtained via 10 fold dilution followed a theoretical Poisson distribution. Four serotypes of Salmonella enterica, three serotypes of enterohaemorrhagic Escherichia coli and one serotype of Listeria monocytogenes were used as sample bacteria. An inoculum of each serotype was prepared via a 10-fold dilution series to obtain bacterial cell counts with mean values of one or two. To determine whether the experimentally obtained bacterial cell counts follow a theoretical Poisson distribution, a likelihood ratio test between the experimentally obtained cell counts and Poisson distribution which parameter estimated by maximum likelihood estimation (MLE) was conducted. The bacterial cell counts of each serotype sufficiently followed a Poisson distribution. Furthermore, to examine the validity of the parameters of Poisson distribution from experimentally obtained bacterial cell counts, we compared these with the parameters of a Poisson distribution that were estimated using random number generation via computer simulation. The Poisson distribution parameters experimentally obtained from bacterial cell counts were within the range of the parameters estimated using a computer simulation. These results demonstrate that the bacterial cell counts of each serotype obtained via 10-fold dilution followed a Poisson distribution. The fact that the frequency of bacterial cell counts follows a Poisson distribution at low number would be applied to some single-cell studies with a few bacterial cells. In particular, the procedure presented in this study enables us to develop an inactivation model at the single-cell level that can estimate the variability of survival bacterial numbers during the bacterial death process. PMID- 27554146 TI - Survival and bioactivities of selected probiotic lactobacilli in yogurt fermentation and cold storage: New insights for developing a bi-functional dairy food. AB - In previous work, we demonstrated that two probiotic strains, namely Lactobacillus casei PRA205 and Lactobacillus rhamnosus PRA331, produce fermented milks with potent angiotensin-converting enzyme (ACE)-inhibitory and antioxidant activities. Here, we tested these strains for the survivability and the release of antihypertensive and antioxidant peptides in yogurt fermentation and cold storage. For these purposes three yogurt batches were compared: one prepared using yogurt starters alone (Lactobacillus delbrueckii subspecies bulgaricus 1932 and Streptococcus thermophilus 99), and the remaining two containing either PRA205 or PRA331 in addition to yogurt starters. Despite the lower viable counts at the fermentation end compared to PRA331, PRA205 overcame PRA331 in survivability during refrigerated storage for 28 days, leading to viable counts (>10(8) CFU/g) higher than the minimum therapeutic threshold (10(6) CFU/g). Analyses of in vitro ACE-inhibitory and antioxidant activities of peptide fractions revealed that yogurt supplemented with PRA205 displays higher amounts of antihypertensive and antioxidant peptides than that produced with PRA331 at the end of fermentation and over storage. Two ACE-inhibitory peptides, Valine Proline-Proline (VPP) and Isoleucine-Proline-Proline (IPP), were identified and quantified. This study demonstrated that L. casei PRA205 could be used as adjunct culture for producing bi-functional yogurt enriched in bioactive peptides and in viable cells, which bring health benefits to the host as probiotics. PMID- 27554147 TI - Quality assessment of ice-stored tropical yellowfin tuna (Thunnus albacares) and influence of vacuum and modified atmosphere packaging. AB - Metagenomic, microbial, chemical and sensory analyses of Thunnus albacares from Martinique stored in ice (AIR - 0 degrees C), vacuum (VP - 4/8 degrees C) and modified atmosphere packaging (MAP - 4/8 degrees C) (70% CO2 - 30% O2) were carried out. The organoleptic rejection of AIR tuna was observed at day 13 when total bacterial counts equaled 10(6)-10(7) CFU g(-1). No extension of shelf-life was provided by VP and MAP. According to 16S rRNA gene sequence analyzed by Illumina MiSeq and PCR-TTGE, Rhodanobacter terrae was the main species of the freshly caught tuna. At the sensory rejection time, Brochothrix thermosphacta and Pseudomonas dominated the AIR products while B. thermosphacta alone or a mix of B. thermosphacta, Enterobacteriaceae and lactic acid bacteria (LAB) dominated the microbiota of MAP and VP products, respectively. The pH value remained stable in all trials, ranging from 5.77 to 5.97. Total volatile basic nitrogen (TVBN) and trimethylamine (TMA-N) concentrations were weak and not significantly different between batches. Lipid oxidation increased in the samples containing O2 (MAP > AIR). The initial concentration of histamine was high (75-78 mg kg(-1)) and stable up to 8 days but then significantly decreased in all trials to reach 25-30 mg kg(-1), probably due to the presence of histamine-decomposing bacteria. PMID- 27554148 TI - Metagenomic analysis of fungal diversity in Korean traditional wheat-based fermentation starter nuruk. AB - Nuruk, a traditional natural starter, is extensively used in the brewing of Makgeolli, one of Korea's most popular alcoholic beverages that has been recently gaining global popularity. Thus, the quality of traditional nuruk needs to be enhanced. The nuruk mycobiome greatly influences both fermentation process as well as palatability enhancement. Limitations of culture-dependent identification restrict an accurate analysis of fungal diversity and distribution in nuruks. 454 pyrosequencing of two traditional wheat-based nuruks, prepared at two representative temperature conditions revealed a total of 153 and 53 OTUs for nuruks A and B, respectively, from a total of 33,157 ITS sequences. Phylogenetic assignments indicated that nuruk A mycobiota was dominated by the genera Aspergillus and Mucorales, whereas nuruk B by Rhizomucor. Species-level identification indicated that Mucorales sp., Aspergillus candidus, and Aspergillus cibarius predominated in nuruk A mycoflora whereas Rhizomucor pusillus, Mucorales sp., and Thermoascus crustaceus in nuruk B. The alpha diversity indices suggest nuruk A mycobiota to be more diverse than that of nuruk B at almost all time points of fermentation. Resemblances of patterns of predominant species composition and succession between culture-dependent and independent phylogenetic analysis creates the potential to reconstruct the nuruk mycobiome in vitro, which allows the establishment of a standard inoculum for scientific comparison. PMID- 27554149 TI - Identification and growth dynamics of meat spoilage microorganisms in modified atmosphere packaged poultry meat by MALDI-TOF MS. AB - Modified atmosphere packaging (MAP) is widely used in food industry to extend the microbiological shelf-life of meat. Typically, poultry meat has been packaged in a CO2/N2 atmosphere (with residual low O2). Recently, some producers use high O2 MAP for poultry meat to empirically reach comparable shelf lifes. In this work, we compared spoilage microbiota of skinless chicken breast in high (80% O2, 20% CO2) and low O2 MAP (65% N2 and 35% CO2). Two batches of meat were incubated in each atmosphere for 14 days at 4 degrees C and 10 degrees C. Atmospheric composition of each pack and colony forming units (25 degrees C, 48 h, BHI agar) of poultry samples were determined at seven timepoints. Identification of spoilage organisms was carried out by MALDI-TOF MS. Brochothrix thermosphacta, Carnobacterium sp. and Pseudomonas sp. were the main organisms found after eight days at 4 degrees C and 10 degrees C in high O2 MAP. In low O2 MAP, the main spoilage microbiota was represented by species Hafnia alvei at 10 degrees C, and genera Carnobacterium sp., Serratia sp., and Yersinia sp. at 4 degrees C. High O2 MAP is suggested as preferential gas because were less detrimental and pathogens like Yersinia were not observed. PMID- 27554150 TI - Improvement of Ayran quality by the selection of autochthonous microbial cultures. AB - Ayran is a traditional Turkish milk drink which is fermented and salted. Inadequate production and storage conditions contribute to its variable organoleptic quality and stability during shelf-life. A thorough physico chemical, nutritional and microbial characterization of artisanal Ayran was carried out in order to standardize its overall quality without altering its original traits. Ayran microbial ecosystem was largely dominated by Streptococcus thermophilus (ST) and Lactobacillus delbrueckii subsp. bulgaricus (LDB). High counts of other lactic acid bacteria species, including Lactobacillus helveticus (LH), Lactobacillus fermentum (LF), and Lactobacillus paracasei (LP), were also found. Selected LDB, LP and LH strains grew well in milk displaying fast acidification and high proteolysis, differently from ST and LF strains that did not cause noticeable changes. A selected autochthonous three-strain culture (TSC), composed of one strain of LDB, LP and ST, was applied for the pilot-scale production of traditional Ayran. The Ayran produced with this TSC resulted in the most extensive shelf-life (one month) and in the best terms of its nutritional and sensory quality nevertheless altering its typical pleasant yogurt and cottage cheese notes. This TSC is at disposal of SMEs who need to standardize the overall quality of this traditional fermented milk, preserving its typical traits. PMID- 27554151 TI - Influence of water activity on inactivation of Escherichia coli O157:H7, Salmonella Typhimurium and Listeria monocytogenes in peanut butter by microwave heating. AB - This study evaluated the efficacy of a 915 MHz microwave with 3 different electric power levels to inactivate three pathogens in peanut butter with different aw. Peanut butter inoculated with Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium and Listeria monocytogenes (0.3, 0.4, and 0.5 aw) were treated with a 915 MHz microwave with 2, 4, and 6 kW for up to 5 min. Six kW 915 MHz microwave treatment for 5 min reduced these three pathogens by 1.97 to >5.17 log CFU/g. Four kW 915 MHz microwave processing for 5 min reduced these pathogens by 0.41-1.98 log CFU/g. Two kW microwave heating did not inactivate pathogens in peanut butter. Weibull and Log-Linear + Shoulder models were used to describe the survival curves of three pathogens because they exhibited shouldering behavior. Td and T5d values were calculated based on the Weibull and Log-Linear + Shoulder models. Td values of the three pathogens were similar to D values of Salmonella subjected to conventional heating at 90 degrees C but T5d values were much shorter than those of conventional heating at 90 degrees C. Generally, increased aw resulted in shorter T5d values of pathogens, but not shorter Td values. The results of this study can be used to optimize microwave heating pasteurization system of peanut butter. PMID- 27554152 TI - Added ingredients affect the microbiota and biochemical characteristics of durum wheat type-I sourdough. AB - This study aimed at understanding the effect of additional ingredients (baker's yeast, macerated pears, grape must, honey, or water from macerated pears) on the microbiota and biochemical characteristics of durum wheat-based sourdough. One dough prepared using only flour was used as the control (control-dough). Compared to the control-dough, doughs containing additional ingredients showed higher (P < 0.05) cell numbers of lactic acid bacteria after the first fermentation. Constant pH of ca. 4.0 was found after two (macerated pears or water pears-doughs) to seven (control-dough) back-slopping steps. The use of additional ingredients caused lower microbial diversity, after the first fermentation and in mature sourdoughs. Regardless of the type of ingredient used, OTU belonging to the genus Lactobacillus represented more than 95% of the total Firmicutes in mature sourdoughs. Some metabolic capacities of microbial community of the mature sourdoughs were linked to the additional ingredient. Based on culture-dependent method, Lactobacillus plantarum and Saccharomyces cerevisiae dominated in all the sourdoughs. However, the sourdoughs showed different strains of these two species. Other lactic acid bacterium species were associated to baker's yeast, grape must and macerated pears. The different microbial composition was correlated (r > 0.7, P < 0.05) with several biochemical characteristics of the sourdoughs (e.g., free amino acids and their derivatives). PMID- 27554153 TI - Comparison and optimization of detection methods for noroviruses in frozen strawberries containing different amounts of RT-PCR inhibitors. AB - Frozen berries have been repeatedly identified as vehicles for norovirus (NoV) transmission causing large gastroenteritis outbreaks. However, virus detection in berries is often hampered by the presence of RT-PCR-inhibiting substances. Here, several virus extraction methods for subsequent real-time RT-PCR-based NoV-RNA detection in strawberries were compared and optimized. NoV recovery rates (RRs) between 0.21 +/- 0.13% and 10.29 +/- 6.03% were found when five different artificially contaminated strawberry batches were analyzed by the ISO/TS15216-2 method indicating the presence of different amounts of RT-PCR inhibitors. A comparison of five different virus extraction methods using artificially contaminated strawberries containing high amounts of RT-PCR inhibitors revealed the best NoV RRs for the ISO/TS15216 method. Further improvement of NoV RRs from 2.83 +/- 2.92% to 15.28 +/- 9.73% was achieved by the additional use of Sephacryl((r))-based columns for RNA purification. Testing of 22 frozen strawberry samples from a batch involved in a gastroenteritis outbreak resulted in 5 vs. 13 NoV GI-positive and in 9 vs. 20 NoV GII-positive samples using the original ISO/TS15216 method vs. the extended protocol, respectively. It can be concluded that the inclusion of an additional RNA purification step can increase NoV detection by the ISO/TS15216-2 method in frozen berries containing high amounts of RT-PCR inhibitors. PMID- 27554154 TI - Modeling the behavior of Listeria monocytogenes during enrichment in half Fraser broth; impact of pooling and the duration of enrichment on the detection of L. monocytogenes in food. AB - A stochastic model describing the growth of Listeria monocytogenes during enrichment in half Fraser was developed for the purpose of estimating the effects of modifications to the first enrichment step of the EN ISO 11290-1 detection method. Information pertaining to the variability of growth rates, physiological state of the cell, and the behavior of individual cells contaminating the food were obtained from previously published studies. We used this model to investigate the impact of pooling enrichment broths (wet pooling) on the performance of the standard method. For validation of the model, the numbers of L. monocytogenes occurring in 88 naturally contaminated foods following pre enrichment were compared to model-simulated microbial counts. The model was then used to perform simulations representative of the natural contamination observed for smoked salmon in the European baseline survey of 2010-2011. The model estimated L. monocytogenes levels following individual enrichment or following the pooling of five broths where only one would be contaminated were compared. The model indicated a 10% loss of method sensitivity resulting from wet pooling. The model also predicted a 5% decrease in the sensitivity of the method when the duration of the enrichment was reduced from 24 to 22 h. PMID- 27554155 TI - A peptidome-based phylogeny pipeline reveals differential peptides at the strain level within Bifidobacterium animalis subsp. lactis. AB - Bifidobacteria are gut commensal microorganisms belonging to the Actinobacteria group. Some specific strains of Bifidobacterium animalis subsp. lactis are used in functional foods as they are able to exert health-promoting effects in the human host. Due to the limited genetic variability within this subspecies, it is sometimes difficult for a manufacturer to properly track its strain once included in dairy products or functional foods. In this paper, we present a peptidome based analysis in which the proteomes of a set of B. animalis subsp. lactis strains were digested in silico with human gut endopeptidases. The molecular masses were compared along all the strains to detect strain-specific peptides. These peptides may be interesting towards the development of methodologies for strain identification in the final product. PMID- 27554156 TI - Influence of in-package cold plasma treatment on microbiological shelf life and appearance of fresh chicken breast fillets. AB - The effect of in-package cold plasmas (CP) was studied on microbiological shelf life and surface lightness of fresh chicken fillets (pectoralis major). Chicken fillets were packaged in food trays in air or modified atmosphere (MA) gas (O2:CO2:N2 = 65:30:5) and stored at 4 degrees C after exposed to an in-package cold plasma (80 kV for 180 s) treatment. Populations of mesophiles, psychrophiles, and pseudomonas spp. were measured as indicators for microbiological shelf life and CIELAB L(*) values as an indicator for raw meat appearance. Results show that regardless of microbial type, there were no significant differences in microbial counts between the control and CP treated chicken fillets packed in air. However, in the MA packages, microbial counts were consistently lower than the non-treated control during refrigerated storage. Regardless of CP treatment, the microbial counts on the samples packed in air were much higher than in MA. They were more than 6 logs cfu/g in air compared to fewer than 4 logs cfu/g in MA after 7 d storage and fewer than 6 logs cfu/g after 14 d storage. Regardless of CP treatment and gas composition in package, there were no significant differences in the surface L(*) value between the fillets pre treatment and those after storage at 4 degrees C. These results demonstrate that the effects of in-package CP treatments on microbiological shelf life of fresh chicken fillets depend upon headspace composition in packages. When fresh chicken fillets are packed in air, CP treatment has no effect on microbiological shelf life. MA packages with high O2 and CO2 significantly extend shelf life and CP treatment with MA can at least double shelf life of fresh chicken meat (more than 14 days). Regardless of headspace composition, in-package CP does not have negative effects on chicken meat appearance. PMID- 27554157 TI - High-throughput screening of a large collection of non-conventional yeasts reveals their potential for aroma formation in food fermentation. AB - Saccharomyces yeast species are currently the most important yeasts involved in industrial-scale food fermentations. However, there are hundreds of other yeast species poorly studied that are highly promising for flavour development, some of which have also been identified in traditional food fermentations. This work explores natural yeast biodiversity in terms of aroma formation, with a particular focus on aromas relevant for industrial fermentations such as wine and beer. Several non-Saccharomyces species produce important aroma compounds such as fusel alcohols derived from the Ehrlich pathway, acetate esters and ethyl esters in significantly higher quantities than the well-known Saccharomyces species. These species are Starmera caribaea, Hanseniaspora guilliermondii, Galactomyces geotrichum, Saccharomycopsis vini and Ambrosiozyma monospora. Certain species revealed a strain-dependent flavour profile while other species were very homogenous in their flavour profiles. Finally, characterization of a selected number of yeast species using valine or leucine as sole nitrogen sources indicates that the mechanisms of regulation of the expression of the Ehrlich pathway exist amongst non-conventional yeast species. PMID- 27554158 TI - Biocide and antibiotic resistance of Enterococcus faecalis and Enterococcus faecium isolated from the swine meat chain. AB - In this study nine strains of Enterococcus faecalis and 12 strains of Enterococcus faecium, isolated from different sample types in the swine meat chain and previously characterized for the presence of antibiotic resistance genes, were examined for phenotypic tolerance to seven biocides (chlorexidine, benzalkonium chloride, triclosan, sodium hypochlorite, 2-propanol, formaldehyde and hydrogen peroxide) and resistance to nine antibiotics (ampicillin, vancomycin, gentamicin, kanamycin, streptomycin, erythromycin, clindamycin, tetracycline and chloramphenicol). Moreover, the presence of efflux system encoding genes qacA/B, qacC, qacE, qacEDelta1, emeA, and stress response genes, sigV and gsp65, involved in the tolerance to biocides, was analysed. Most strains were not tolerant to the biocides, but showed minimum inhibitory concentrations (MICs) higher than the recommended cut-off values for all the antibiotics tested, except for vancomycin and chloramphenicol. Only weak correlations, if any, were found between biocide and antibiotic resistance data. One E. faecalis strain was tolerant to triclosan and one E. faecium strain, with higher tolerance to chlorexidine than the other strains tested, was found to carry a qacA/B gene. Our results indicated that phenotypic resistance to antibiotics is very frequent in enterococcal isolates from the swine meat chain, but phenotypic tolerance to biocides is not common. On the other hand, the gene qacA/B was found for the first time in the species E. faecium, an indication of the necessity to adopt measures suitable to control the spread of biocide resistance determinants among enterococci. PMID- 27554159 TI - Application of high pressure processing for controlling Clostridium tyrobutyricum and late blowing defect on semi-hard cheese. AB - In this study we evaluated the application of different high pressure (HP) treatments (200-500 MPa at 14 degrees C for 10 min) to industrial sized semi hard cheeses on day 7, with the aim of controlling two Clostridium tyrobutyricum strains causing butyric acid fermentation and cheese late blowing defect (LBD). Clostridium metabolism and LBD appearance in cheeses were monitored by sensory (cheese swelling, cracks/splits, off-odours) and instrumental analyses (organic acids by HPLC and volatile compounds by SPME/GC-MS) after 60 days. Cheeses with clostridial spores HP-untreated and HP-treated at 200 MPa showed visible LBD symptoms, lower concentrations of lactic, citric and acetic acids, and higher levels of pyruvic, propionic and butyric acids and of 1-butanol, ethyl and methyl butanoate, and ethyl pentanoate than cheeses without spores. However, cheeses with clostridial spores and HP-treated at >= 300 MPa did not show LBD symptoms and their organic acids and volatile compounds profiles were comparable to those of their respective HP-treated control cheeses, despite HP treatments caused a low spore reduction. A decrease in C. tyrobutyricum spore counts was observed after curd pressing, which seems to indicate an early spore germination, suggesting that HP treatments >=300 MPa were able to inactivate the emerged C. tyrobutyricum vegetative cells and, thereby, prevent LBD. PMID- 27554160 TI - Code stroke: Can we improve response times? PMID- 27554161 TI - Addenbrooke's Cognitive Examination III: a neuropsychological test useful to screen and obtain a cognitive profile. PMID- 27554162 TI - Trends in stroke hospitalisation rates and in-hospital mortality in Aragon, 1998 2010. AB - INTRODUCTION: Despite the impact of cerebrovascular disease (CVD) on global health, its morbidity and time trends in Spain are not precisely known. OBJECTIVE: The purpose of our study was to characterise the epidemiology and trends pertaining to stroke in Aragon over the period 1998-2010. METHODS: We conducted a retrospective, descriptive study using the data of the Spanish health system's Minimum Data Set and included all stroke patients admitted to acute care hospitals in Aragon between 1 January 1998 and 31 December 2010. We present data globally and broken down by stroke subtype, sex, and age group. RESULTS: The number of cases increased by 13% whereas age- and sex-adjusted hospitalisation rates showed a significant decrease for all types of stroke (mean annual decrease of 1.6%). Men and women in younger age groups showed opposite trends in hospitalisation rates for ischaemic stroke. Case fatality rate at 28 days (17.9%) was higher in patients with intracerebral haemorrhage (35.8%) than in those with subarachnoid haemorrhage (26.2%) or ischaemic stroke (13%). CVD case fatality showed a mean annual decline of 2.8%, at the expense of the fatality rate of ischaemic stroke, and it was more pronounced in men than in women. DISCUSSION: Understanding stroke epidemiology and trends at the regional level will help establish an efficient monitoring system and design appropriate strategies for health planning. PMID- 27554163 TI - Understanding the meaning and role of gifts given to Ugandan mothers in maternity care settings: 'The help they give when they've seen how different you are'. AB - The provision of gifts to new mothers in Uganda is laden with significance that varies by the social location of the giver and receiver and the context and conditions under which the gift is made available. Here, we examine the act of gift giving and receiving within a Ugandan maternity care setting, describing the connections between these material objects and social relations. A study investigating the social organisation of maternity care in post-conflict northern Uganda found that gift-giving to new mothers functioned to create a material and discursive context wherein women's desire to access these goods was leveraged to create an incentive to attend formal maternity care during pregnancy and for delivery. In this article we describe the material and discursive processes surrounding gift-giving to new mothers in this global South health care setting. This article contributes critical analyses of the function of gifts in healthcare settings as constructing shared identities, social differences and normative values about health citizenship, and an incentive politic that affects equitable access to maternity care. Drawing on intersectional theory and analysis of how specific practices function ideologically to reward or incentivise pregnant women, we integrate material culture studies into the sociology of women's reproductive health. PMID- 27554165 TI - A sister of PIN1 gene in tomato (Solanum lycopersicum) defines leaf and flower organ initiation patterns by maintaining epidermal auxin flux. AB - The spatiotemporal localization of the plant hormone auxin acts as a positional cue during early leaf and flower organogenesis. One of the main contributors to auxin localization is the auxin efflux carrier PIN-FORMED1 (PIN1). Phylogenetic analysis has revealed that PIN1 genes are split into two sister clades; PIN1 and the relatively uncharacterized Sister-Of-PIN1 (SoPIN1). In this paper we identify entire-2 as a loss-of-function SlSoPIN1a (Solyc10g078370) mutant in Solanum lycopersicum. The entire-2 plants are unable to specify proper leaf initiation leading to a frequent switch from the wild type spiral phyllotactic pattern to distichous and decussate patterns. Leaves in entire-2 are large and less complex and the leaflets display spatial deformities in lamina expansion, vascular development, and margin specification. During sympodial growth in entire-2 the specification of organ position and identity is greatly affected resulting in variable branching patterns on the main sympodial and inflorescence axes. To understand how SlSoPIN1a functions in establishing proper auxin maxima we used the auxin signaling reporter DR5: Venus to visualize differences in auxin localization between entire-2 and wild type. DR5: Venus visualization shows a widening of auxin localization which spreads to subepidermal tissue layers during early leaf and flower organogenesis, showing that SoPIN1 functions to focus auxin signaling to the epidermal layer. The striking spatial deformities observed in entire-2 help provide a mechanistic framework for explaining the function of the SoPIN1 clade in S.lycopersicum. PMID- 27554166 TI - Mespaa can potently induce cardiac fates in zebrafish. AB - The Mesp family of transcription factors have been implicated in the early formation and migration of the cardiac lineage, although the precise molecular mechanisms underlying this process remain unknown. In this study we examine the function of Mesp family members in zebrafish cardiac development and find that Mespaa is remarkably efficient at promoting cardiac fates in normally non cardiogenic cells. However, Mespaa is dispensable for normal cardiac formation. Despite no overt defects in cardiovascular specification, we find a consistent defect in cardiac laterality in mespaa null embryos. This is further exacerbated by the depletion of other mesp paralogues, highlighting a conserved role for the mesp family in left-right asymmetry, distinct from a function in cardiac specification. Despite an early requirement for mespaa to promote cardiogenesis, cells over-expressing mespaa are found to both exhibit unique cellular behaviors and activate the transcription of gata5 only after the completion of gastrulation. We propose that while mespaa remains capable of driving cardiac progenitor formation in zebrafish, it may not play an essential role in the cardiac regulatory network. Furthermore, the late activation of migration and cardiac gene transcription in mespaa over-expressing cells challenges previous studies on the timing of these events and provides intriguing questions for future study. PMID- 27554164 TI - The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9. AB - Acute myelogenous leukemia (AML) is a high-risk hematopoietic malignancy caused by a variety of mutations, including genes encoding the cohesin complex. Recent studies have demonstrated that reduction in cohesin complex levels leads to enhanced self-renewal in hematopoietic stem and progenitors (HSPCs). We sought to delineate the molecular mechanisms by which cohesin mutations promote enhanced HSPC self-renewal as this represents a critical initial step during leukemic transformation. We verified that RNAi against the cohesin subunit Rad21 causes enhanced self-renewal of HSPCs in vitro through derepression of polycomb repressive complex 2 (PRC2) target genes, including Hoxa7 and Hoxa9. Importantly, knockdown of either Hoxa7 or Hoxa9 suppressed self-renewal, implying that both are critical downstream effectors of reduced cohesin levels. We further demonstrate that the cohesin and PRC2 complexes interact and are bound in close proximity to Hoxa7 and Hoxa9. Rad21 depletion resulted in decreased levels of H3K27me3 at the Hoxa7 and Hoxa9 promoters, consistent with Rad21 being critical to proper gene silencing by recruiting the PRC2 complex. Our data demonstrates that the cohesin complex regulates PRC2 targeting to silence Hoxa7 and Hoxa9 and negatively regulate self-renewal. Our studies identify a novel epigenetic mechanism underlying leukemogenesis in AML patients with cohesin mutations. PMID- 27554167 TI - Cup regulates oskar mRNA stability during oogenesis. AB - The proper regulation of the localization, translation, and stability of maternally deposited transcripts is essential for embryonic development in many organisms. These different forms of regulation are mediated by the various protein subunits of the ribonucleoprotein (RNP) complexes that assemble on maternal mRNAs. However, while many of the subunits that regulate the localization and translation of maternal transcripts have been identified, relatively little is known about how maternal mRNAs are stockpiled and stored in a stable form to support early development. One of the best characterized regulators of maternal transcripts is Cup - a broadly conserved component of the maternal RNP complex that in Drosophila acts as a translational repressor of the localized message oskar. In this study, we have found that loss of cup disrupts the localization of both the oskar mRNA and its associated proteins to the posterior pole of the developing oocyte. This defect is not due to a failure to specify the oocyte or to disruption of RNP transport. Rather, the localization defects are due to a drop in oskar mRNA levels in cup mutant egg chambers. Thus, in addition to its role in regulating oskar mRNA translation, Cup also plays a critical role in controlling the stability of the oskar transcript. This suggests that Cup is ideally positioned to coordinate the translational control function of the maternal RNP complex with its role in storing maternal transcripts in a stable form. PMID- 27554169 TI - Counter-perfume: using pheromones to prevent female remating. AB - Strong selection to secure paternity in polyandrous species leads to the evolution of numerous chemicals in the male's seminal content. These include antiaphrodisiac pheromones, which are transmitted from the male to the female during mating to render her unattractive to subsequent males. An increasing number of species have been shown to use these chemicals. Herein, I examine the taxonomic distribution of species using antiaphrodisiac pheromones, the selection pressures driving their evolution in both males and females, and the ecological interactions in which these pheromones are involved. The literature review shows a highly skewed distribution of antiaphrodisiac use; all species currently known to use them are insects with the exception of the garter snakes Thamnophis sirtalis parietalis and T. radix. Nonetheless, many taxa have not yet been tested for the presence of antiaphrodisiacs, in groups both closely and distantly related to species known to express them. Within the Insecta, there have been multiple cases of convergent evolution of antiaphrodisiac pheromones using different chemical compounds and methods of transmission. Antiaphrodisiacs usually benefit males, but their effect on females is variable as they can either prevent them from mating multiple times or help them reduce male harassment when they are unreceptive. Some indirect costs of antiaphrodisiacs also impact both males and females, but more research is needed to determine how general this pattern is. Additional research is also important to understand how antiaphrodisiacs interact with the reproductive biology and sexual communication in different species. PMID- 27554168 TI - Graft-infiltrating host dendritic cells play a key role in organ transplant rejection. AB - Successful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells. We show that donor DCs that accompany heart or kidney grafts are rapidly replaced by recipient DCs. The DCs originate from non-classical monocytes and form stable, cognate interactions with effector T cells in the graft. Eliminating recipient DCs reduces the proliferation and survival of graft-infiltrating T cells and abrogates ongoing rejection or rejection mediated by transferred effector T cells. Therefore, host DCs that infiltrate transplanted organs sustain the alloimmune response after T cell activation has already occurred. Targeting these cells provides a means for preventing or treating rejection. PMID- 27554170 TI - The impact of parenting styles on children developmental outcome: The role of academic self-concept as a mediator. AB - Although the importance of parenting styles directly influencing child development is well established, fewer studied have examined whether parenting styles also affect children's behavioural problems indirectly, mediated through children's academic self-concept (ASC). We examined direct and shared effects of parenting styles on behavioural problems of 199 Kurdish primary school children with a mean age of 11 years 7 months (range 11 years 5 months to 12 years 3 months). Questionnaires measured parenting styles (child version of Alabama Parenting Questionnaire), assessed children's ASC (Myself-As-Learner Scale) and identified children's behavioural problems with the Strengths and Difficulties Questionnaire (SDQ). PROCESS analysis was used to perform the mediation analysis. The results revealed that positive and negative parenting composites are indirectly related to children's internalising behaviour problems. In addition, ASC partially mediated the relationship between the negative parenting composite and prosocial behaviour. However, the mediation analysis did not show the expected indirect effect of parenting styles on externalising problems as being mediated via ASC. Hence, we argue that the ASC serves as a significant mediator in the relationship between parenting styles with prosocial behaviour and internalising problems. PMID- 27554171 TI - Advances in the application of food emulsifier alpha-gel phases: Saturated monoglycerides, polyglycerol fatty acid esters, and their derivatives. AB - Emulsifiers form complex structures in colloidal systems. One of these structures, the alpha-gel phase, has drawn much research interest. alpha-gel phases are formed by emulsifiers that are stable in the alpha-crystalline structure in the presence of water. The alpha-gel phase has shown superior functionality in a variety of applications because it has a water-rich lamellar structure. Even though studies on emulsifier alpha-gel phases emerged over half a century ago, there is still a knowledge gap on fundamental properties of alpha gel phases formed by a variety of emulsifiers. This article summarizes recent studies on the physical and chemical properties of alpha-gel phases formed by several food emulsifiers, specifically saturated monoglycerides, polyglycerol monoester and diesters of fatty acid, and sodium stearoyl lactylate. Recent research has advanced the understanding of factors affecting the stability and foamability of the alpha-gel phases. Current and potential applications of alpha gel phases in baked food products and in personal care products are also reviewed here. PMID- 27554172 TI - Pulsed laser ablation based synthesis of colloidal metal nanoparticles for catalytic applications. AB - Nowadays, metal nanoparticles (NPs) have been considered as highly promising functional materials, impacting virtually all the fields of science and technologies. Numerous wet-chemical approaches have been developed to synthesize metal NPs with various components and structures. Although successful, impurities, such as additives and reaction residuals, usually remain in products. Recently, an alternative method, pulsed laser ablation in liquid (PLAL) phase has attracted increasing attention for colloidal NP preparation, since it can realize a chemical-free environment, leading to the formation of a "clean" NP dispersion. This unique feature makes the PLAL method and resulting metal NPs extremely attractive for catalytic applications, since catalytic reaction efficiency is strongly dependent on the surface feature of metal NPs. Usually, a surfactant free, "bare" metal surface is highly desired for catalysis as it favors the access of the reactants to the surface active sites of metal NPs. Due to the absence of ligand or stabilizer molecules on the surface of PLAL-NPs, it is expected that these PLAL-NPs can exhibit higher catalytic activity in comparison to their chemically synthesized counterparts. In this review, we briefly introduce some recent advances on the synthesis of PLAL-metal NPs and some of their important catalytic applications. PMID- 27554173 TI - Bifunctional Fe3O4/Ag nanoparticles obtained by two-step laser ablation in pure water. AB - HYPOTHESIS: Bimetallic nanoparticles made of iron oxide and Ag could be fabricated by pulsed laser ablation of iron and silver targets in pure water by a two-step route. These nanoparticles could exhibit both magnetic and plasmonic properties. EXPERIMENTS: Bimetallic nanoparticles were fabricated by using a focused Nd:YAG nanosecond laser source emitting a 1064nm wavelength radiation and characterized with zeta-potential, Dynamic Light Scattering (DLS), UV-vis absorption, Transmission Electron Microscopy (TEM), High Resolution TEM (HRTEM), Energy Dispersive X-ray Spectrometry (EDX), and Selected Area Electron Diffraction (SAED). The magnetic character of the nanoparticles was ascertained by observing attraction by a magnet and complete removing from the water environment, while their SERS (surface-enhanced Raman scattering) response was checked by decorating them with 2,2'-bipyridine as molecular reporter and performing Raman tests with green (514.5nm) and far-red (785nm) excitation wavelengths. FINDINGS: The observed magnetic attraction was due to magnetite (Fe3O4), the only ferromagnetic iron oxide form evidenced by the characterization tests in the aqueous colloidal system, where silver nanoparticles were also embedded. UV-vis and SERS spectra confirmed the presence of nanostructured silver as plasmonic constituent of the fabricated metal nanoparticles. PMID- 27554174 TI - Pulsed laser ablation in liquids: Impact of the bubble dynamics on particle formation. AB - Pulsed laser ablation in liquids (PLAL) is a multiscale process, involving multiple mutually interacting phenomena. In order to synthesize nanoparticles with well-defined properties it is important to understand the dynamics of the underlying structure evolution. We use visible-light stroboscopic imaging and X ray radiography to investigate the dynamics occurring during PLAL of silver and gold on a macroscopic scale, whilst X-ray small angle scattering is utilized to deepen the understanding on particle genesis. By comparing our results with earlier reports we can elucidate the role of the cavitation bubble. We find that symmetry breaking at the liquid-solid interface is a critical factor for bubble motion and that the bubble motion acts on the particle distribution as confinement and retraction force to create secondary agglomerates. PMID- 27554175 TI - Laser processing of TiO2 colloids for an enhanced photocatalytic water splitting activity. AB - We have measured the photocatalytic water splitting activity of several titania colloids, modified by nanosecond pulsed laser irradiation. Photocatalysis has been tested using UV and visible light. We have found that laser irradiation increases the hydrogen production efficiency up to a factor of three for anatase, rutile and P25. A hydrogen production rate as high as 30mmolg-1h-1 has been obtained with good stability, tested by repeated runs. The chemical and morphological properties of the nanoparticles have been studied by electron microscopy, X-ray photoelectron spectroscopy and Raman spectroscopy, showing that laser irradiation promotes the formation of disordered surface state and lattice distortion which could be responsible for the observed enhanced photocatalytic activity. PMID- 27554177 TI - The UVB-vitamin D3 -pigment hypothesis is alive and well. PMID- 27554176 TI - Preclinical disease activity in multiple sclerosis: A prospective study of cognitive performance prior to first symptom. AB - OBJECTIVE: To prospectively investigate potential signs of preclinical multiple sclerosis (MS) activity and when they are present prior to first symptom using data from a historical cohort. METHODS: We linked the cognitive performance of all Norwegian men born 1950-1995 who underwent conscription examination at age 18 to 19 years to the Norwegian MS registry to identify those later developing MS, and randomly selected controls frequency-matched on year of birth from the Norwegian Conscript Service database. In this nested case-control study, cognitive test scores were available for 924 male cases and 19,530 male controls. We estimated mean score differences among cases and controls (Student t test) and the risk of developing MS comparing lower to higher scores (Cox regression) in strata of years to clinical onset. RESULTS: Men developing first clinical MS symptoms up to 2 years after the examination scored significantly lower than controls (Delta = 0.80, p = 0.0095), corresponding to a 6 intelligence quotient (IQ)-point difference. Those scoring lowest, that is, >1 standard deviation below the controls' mean, had an increased MS risk during the 2 following years (relative risk = 2.81, 95% confidence interval = 1.52-5.20). Whereas results were similar for relapsing-remitting MS cases (RRMS), those developing primary progressive MS (PPMS) scored a significant 4.6 to 6.9 IQ points lower than controls up to 20 years prior to first progressive symptoms. INTERPRETATION: RRMS may start years prior to clinical presentation, and disease processes in PPMS could start decades prior to first apparent progressive symptoms. Cognitive problems could be present in both MS forms before apparent symptoms. Apart from potential implications for clinical practice and research, these findings challenge our thinking about the disease. Ann Neurol 2016;80:616-624. PMID- 27554178 TI - Predictors and risk factors of hypoparathyroidism after total thyroidectomy. AB - BACKGROUND: The aim of this study was to evaluate the risk factors for hypoparathyroidism after total thyroidectomy and to determine whether early postoperative serum levels of calcium and phosphorus could be used to predict its development. MATERIALS AND METHODS: The study group consisted of 1030 patients who had undergone total thyroidectomy at our institution between March 2008 and July 2014. The clinicopathologic characteristics, indications for the operation, and surgical details of normocalcemic and hypocalcemic patients were compared, and variations in serum calcium and phosphorus levels were measured every day after the operation. RESULTS: Of the 1030 patients, 291 (28.2%) were found to have transient hypocalcemia and 27 (2.6%) had permanent hypocalcemia. On univariate analysis, younger age (P = 0.001), female gender (P < 0.001), longer operative time (P = 0.009), extent of central neck dissection (CND) (P = 0.003), and malignancy (P = 0.005) were found to be significantly associated with transient hypocalcemia. On multivariate analysis, female gender (P = 0.001), extent of CND (P = 0.017), and the identification of parathyroid gland (PTG) tissue in permanent pathologic sections were significant factors. In addition, the occurrence of postoperative hypocalcemia was correlated with relative changes in serum calcium and phosphorus levels. Patients whose serum calcium levels decreased over 20% on postoperative day 2 were more likely to develop hypoparathyroidism, with 92% specificity. CONCLUSION: Female gender (P = 0.001), extent of CND (P = 0.014), and PTG in permanent pathologic sections (P = 0.035) were found to be significant factors affecting the development of hypocalcemia. Despite some study limitations, we suggest that the relative changes in the serum levels of calcium (20%) and of phosphorus (40%) on the second postoperative day may be reliable predictors of post-thyroidectomy hypoparathyroidism. PMID- 27554179 TI - Is routine dissection of the station 9 lymph nodes really necessary for primary lung cancer? AB - OBJECTIVES: Mediastinal lymph node dissection is an essential component of lung cancer surgery; however, choosing mediastinal lymph nodes stations to be dissected is subjective. We carried out this research to investigate the need for dissection of station 9 lymph nodes during lung cancer surgery. METHODS: Patients with primary lung cancer who underwent radical surgery between 2010 and 2014 were retrospectively reviewed. Clinical, pathologic, and prognosis data were obtained and analyzed. RESULTS: A total number of 1397 patients were included in this research. The metastasis rate of station 9 was 3.45%, which was significantly lower than other mediastinal stations. This metastasis rate was significantly correlated with pT stage, the lobe where the tumor was located, metastasis status of intrapulmonary lymph nodes, pTNM stage, and most of the other mediastinal lymph node stations. In males or ground glass opacity (GGO) patients, the metastasis of station 9 nodes was more unlikely to occur, even though there was no statistical significance. The staging results of most patients (99.63%) would not be impaired, even if station 9 nodes were not dissected, and the prognostic analysis showed that the metastasis status of station 9 had no significant influence on survival. CONCLUSION: The metastasis rate of station 9 lymph nodes was significantly lower than other mediastinal stations in lung cancer patients. The metastasis status of station 9 had no significant influence on tumor staging or prognosis. Routine dissection of station 9 lymph nodes may not be necessary, especially in patients with a low T stage, upper or middle lobe tumors, or without intrapulmonary lymph node metastasis. PMID- 27554180 TI - The diagnostic performance of ultrasound for acute appendicitis in pregnant and young nonpregnant women: A case-control study. AB - BACKGROUND: Ultrasonography is frequently used to diagnose acute appendicitis in women of reproductive age, but its diagnostic value in pregnant patients remains unclear. This study sought to compare the diagnostic performance of ultrasound in pregnant and young nonpregnant women with suspected acute appendicitis. METHODS: The database of a single tertiary medical center was reviewed for all women of reproductive age who underwent appendectomy either during pregnancy (2000-2014) or in the nonpregnant state (2004-2007) following ultrasound evaluation. The performance of ultrasound in terms of predicting the final pathologic diagnosis was compared between the pregnant and non pregnant groups using receiver operating characteristic curve analysis. RESULTS: Of 586 young women treated for appendicitis during the study periods (92 pregnant, 494 non-pregnant), 200 underwent preoperative ultrasound [67 pregnant, and 133 nonpregnant young women]. The pregnant and nonpregnant groups were comparable in age and presenting symptoms. There was no significant difference in the predictive performance of ultrasound between the two groups (AUC 0.76 and 0.73 respectively, p = 0.78) or within the pregnant group, by trimester [first (n = 23), AUC 0.73; second (n = 32), AUC 0.67; third (n = 12), AUC 0.86; p = 0.4]. Ultrasound had a positive predictive value of 0.94 in the pregnant group and 0.91 in the nonpregnant group; corresponding negative predictive values were 0.40 and 0.43. CONCLUSIONS: There appears to be no difference in the ability of ultrasound to predict the diagnosis of acute appendicitis between pregnant women and nonpregnant women of reproductive age. Therefore, similar preoperative imaging algorithms may be used in both patient populations. PMID- 27554181 TI - Coping with unpleasant knowledge: Meat eating among students of environmental studies. AB - This paper presents qualitative research on the attitudes and behaviors of environmental studies graduate students toward meat eating, and their strategies for coping with the cognitive dissonance induced by the issues related to meat eating and production. The research draws on theoretical and empirical research on the issue of meat eating and the psychological processes involved in it, and by analyzing in-depth interviews it reveals that these students exhibit partially different coping strategies than what studies on general population show, as a result of their awareness and their social circle. The results show that even though these people do not usually regard meat eating as wrong or undesirable in principle, they are well aware of the ethical and environmental issues related to it. In their attitudes and behavior the students are significantly influenced by their friends and fellow students amongst whom they perceive avoiding meat as a social norm. A generalization of the results suggests that the psychological dynamics of meat eating among environmentally informed and engaged people in general may be different than in general population. Further research into this group of people is proposed, most importantly from a socio-cultural point of view. PMID- 27554182 TI - Consumers' environmental and ethical consciousness and the use of the related food products information: The role of perceived consumer effectiveness. AB - Consumers can be important active contributors to a sustainable society by selecting food choices that are both healthy and produced respecting environmental and socially ethical standards. The current study investigates five consumer behavioural factors - namely, perceived consumer effectiveness (PCE); environmental conscious behaviour; concerns for ethical food production; health conscious lifestyle; and healthy dietary patterns. The key interest of the study lies in exploring the moderating role of PCE - the extent to which the consumer believes that his/her own efforts can make a difference - in these interrelationships. The empirical analysis was conducted through an online survey of food consumers implemented in three markets - the US, the UK and Germany. Findings indicate that for individuals with higher levels of PCE, who are environmental conscious and ethically concerned, information on food labels relating to environmental and social issues represents value by itself. Interestingly, health and nutrition information on food labels was not perceived valuable by consumers with high PCE. The predictive effects of various socio demographic variables on PCE, consumer environmental and health consciousness are discussed. Cross-cultural differences are also outlined. The results of this research may contribute to the development of environmental policies and communication strategies of the food industry to enhance perceived consumer effectiveness among consumers. Improved PCE, in turn, may catalyze consumers' environmental behaviour and ethical concerns in relation to consumption of food products with environmental and social information. PMID- 27554183 TI - Awakening to the politics of food: Politicized diet as social identity. AB - In this qualitative study, the process of developing a politicized identity around diet was explored through a social psychological lens. Applying one of the most influencial models of group identity development proposed by Cross (1978) in which an "encounter" experience spurs an awakening into a politicized identity, we asked 36 participants who followed alternative diets due to political reasons to describe their unique encounter experiences that brought them to their politicized awakening. Their self-identified diets included pescetarian, vegetarian, vegan, raw, non-GMO/organic, and reduced meat consumption. Participants described the rationale for their diets, their "encounter" or awakening to their politicized diets, and whether they viewed their diet as a part of their identity. Using thematic analysis, we identified four key types of encounters that sparked their politicization: a series of integrated events, exposure to educational materials, a direct visceral emotional experience, and guidance from a role model. We discuss the results with regard to the politics of food, the nature of the politicized dieter's identity as part of a minority food culture, and the difficulties of engaging in political action through one's diet. The underexplored benefits of applying social psychological theories of identity to research on dietary subcultures is also discussed. PMID- 27554184 TI - Association between objective and subjective binge eating and psychopathology during a psychological treatment trial for bulimic symptoms. AB - Although loss of control (LOC) while eating is a core construct of bulimia nervosa (BN), questions remain regarding its validity and prognostic significance independent of overeating. We examined trajectories of objective and subjective binge eating (OBE and SBE, respectively; i.e., LOC eating episodes involving an objectively or subjectively large amount of food) among adults participating in psychological treatments for BN-spectrum disorders (n = 80). We also explored whether changes in the frequency of these eating episodes differentially predicted changes in eating-related and general psychopathology and, conversely, whether changes in eating-related and general psychopathology predicted differential changes in the frequency of these eating episodes. Linear mixed models with repeated measures revealed that OBE decreased twice as rapidly as SBE throughout treatment and 4-month follow-up. Generalized linear models revealed that baseline to end-of-treatment reductions in SBE frequency predicted baseline to 4-month follow-up changes in eating-related psychopathology, depression, and anxiety, while changes in OBE frequency were not predictive of psychopathology at 4-month follow-up. Zero-inflation models indicated that baseline to end-of treatment changes in eating-related psychopathology and depression symptoms predicted baseline to 4-month follow-up changes in OBE frequency, while changes in anxiety and self-esteem did not. Baseline to end-of-treatment changes in eating-related psychopathology, self-esteem, and anxiety predicted baseline to 4 month follow-up changes in SBE frequency, while baseline to end-of-treatment changes in depression did not. Based on these findings, LOC accompanied by objective overeating may reflect distress at having consumed an objectively large amount of food, whereas LOC accompanied by subjective overeating may reflect more generalized distress related to one's eating- and mood-related psychopathology. BN treatments should comprehensively target LOC eating and related psychopathology, particularly in the context of subjectively large episodes, to improve global outcomes. PMID- 27554185 TI - Maternal characteristics associated with the obesogenic quality of the home environment in early childhood. AB - The home environment is likely to influence children's diet and activity patterns and ultimately, their weight trajectories. Identifying family characteristics associated with a more 'obesogenic' home can provide insight into the determinants, and has implications for targeting and tailoring strategies to promote healthier lifestyles. The present study examined maternal characteristics associated with a more obesogenic home environment in 1113 families with preschool children. Primary caregivers (99% mothers) from the Gemini cohort completed the Home Environment Interview (HEI) when their children were 4 years old. Maternal demographics and BMI were assessed in the Gemini baseline questionnaire when the children were on average 8 months old. Maternal eating style was assessed when the children were on average 2 years old, using the Dutch Eating Behaviour Questionnaire (DEBQ). Responses to the HEI were standardised and summed to create a composite score of the obesogenic quality of the home; this was categorised into tertiles. Multivariate ordinal logistic regression showed that mothers who were younger (adjusted OR; 95% CI = 0.96; 0.94-0.98), less educated (1.97; 1.40-2.77), and had lower incomes (1.89; 1.43-2.49) at baseline were more likely to live in an obesogenic home environment at 4 years, as were mothers who scored higher on the DEBQ External Eating scale (1.40; 1.16-1.70) at 2 years, and had a higher baseline BMI (1.05; 1.02-1.08). Using a novel, composite measure of the home environment, this study finds that families who are more socio-economically deprived, and where the mothers are themselves heavier and have a more food responsive eating style, tend to provide a home environment with the hallmarks of a higher risk of weight gain. PMID- 27554186 TI - Licence to eat: Information on energy expended during exercise affects subsequent energy intake. AB - An acute bout of exercise, compared with no exercise, appears to have little influence on subsequent energy intake (EI), resulting in short-term negative energy balance. Whereas the labelling of food is evidenced to influence EI, little research has focused on how EI is affected by framing acute exercise in different ways. To explore this, 70 healthy, mostly lean, male and female participants in the current study completed a set amount of exercise (estimated energy expenditure (EE) 120 kcal), but were informed on three occasions before and after the exercise that they had expended either 50 kcal or 265 kcal. An ad libitum test meal, comprising orange juice, tortilla chips and chocolate chip cookies, was then presented after a 10-min break to assess subsequent EI. Measures of hunger and dietary restraint were also completed. Greater EI, primarily driven by chocolate chip cookie consumption (p = 0.015), was observed in participants receiving 265 kcal EE information. Hunger ratings were significantly lower in the 265 kcal EE information group than in the 50 kcal group following the test meal (p = 0.035), but not immediately after the exercise. These results support an interpretation that higher EE information (265 kcal) provides participants with a greater 'licence to eat' when palatable foods are accessible. Tentative evidence for a moderating effect of dietary restraint was observed, indicating a greater influence of EE information in participants with lower restraint. The findings of the current study suggest that the provision of EE information (e.g., through mobile device apps) could be counter productive to healthy weight management. PMID- 27554188 TI - Translation of fetal abdominal circumference-guided therapy of gestational diabetes complicated by maternal obesity to a clinical outpatient setting. AB - OBJECTIVE: To evaluate the effectiveness of fetal abdominal circumference-guided therapy for gestational diabetes (GDM) in an outpatient population characterized by highly-prevalent maternal obesity. METHODS: Data for this translational retrospective cohort study come from medical records. Fetal abdominal circumference was assessed by ultrasound in late second trimester, and sex- and gestational age-specific percentiles assigned. Taking fetal abdominal circumference percentile as a marker for adequacy of fetal growth, maternal glucose targets were set accordingly: loose, moderate or tight. Associations between mother's targets and neonatal outcomes (small for gestational age (SGA), large for gestational age (LGA), macrosomia, neonatal intensive care unit (NICU) admission, and neonatal hypoglycemia) were assessed using unconditional logistic regression, controlling for pre-gravid body mass index (BMI) and gestational weight gain. RESULTS: In 419 consecutive pregnancies complicated by GDM, neonatal outcomes compared favorably with previous randomized trials of intensive GDM management. Importantly, adverse outcomes were observed less often than might be expected in an obese GDM population. BMI did not have an independent effect on neonatal outcomes. CONCLUSIONS: Ultrasound-guided therapy of GDM, in general clinic use, can limit excess macrosomia and LGA, even in a population with significant maternal obesity. PMID- 27554189 TI - Composition and emission dynamics of migratory locust volatiles in response to changes in developmental stages and population density. AB - Chemical communication plays an important role in density-dependent phase change in locusts. However, the volatile components and emission patterns of the migratory locust, Locusta migratoria, are largely unknown. In this study, we identified the chemical compositions and emission dynamics of locust volatiles from the body and feces and associated them with developmental stages, sexes and phase changes. The migratory locust shares a number of volatile components with the desert locust (Schistocerca gregaria), but the emission dynamics of the two locust species are significantly different. The body odors of the gregarious nymphs in the migratory locust consisted of phenylacetonitrile (PAN), benzaldehyde, guaiacol, phenol, aliphatic acids and 2,3-butanediol, and PAN was the dominant volatile. Volatiles from the fecal pellets of the nymphs primarily consist of guaiacol and phenol. Principal component analysis (PCA) showed significant differences in the volatile profiles between gregarious and solitary locusts. PAN and 4-vinylanisole concentrations were significantly higher in gregarious individuals than in solitary locusts. Gregarious mature males released significantly higher amounts of PAN and 4-vinylanisole during adulthood than mature females and immature adults of both sexes. Furthermore, PAN and 4 vinylanisole were completely lost in gregarious nymphs during the solitarization process, but were obtained by solitary nymphs during gregarization. The amounts of benzaldehyde, guaiacol and phenol only unidirectionally decreased from solitary to crowded treatment. Aliphatic aldehydes (C7 to C10), which were previously reported as locust volatiles, are now identified as environmental contaminants. Therefore, our results illustrate the precise odor profiles of migratory locusts during developmental stages, sexes and phase change. However, the function and role of PAN and other aromatic compounds during phase transition need further investigation. PMID- 27554190 TI - The Efficacy of Cognitive Behavioral Therapy for Adults With ADHD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - OBJECTIVE: To systematically review the literature on published randomized controlled trials (RCTs) of cognitive behavioral therapy (CBT) for adult ADHD and to establish the effectiveness of CBT in reducing ADHD symptoms. METHOD: A systematic review of nine RCTs and two subsequent meta-analyses of eight of the studies were conducted. RESULTS: Just nine studies were identified, of generally good quality but with some limitations. Four trials (total N = 160) compared CBT with waiting list controls, and three trials (total N = 191) compared CBT with appropriate active control groups. Meta-analyses showed that CBT was superior to waiting list with a moderate to large effect size (standardized mean difference [SMD] = 0.76, 95% confidence interval [CI] [0.21, 1.31], p = .006) and superior to active control groups with a small to moderate effect size (SMD = 0.43, 95% CI [0.14, 0.71], p = .004). CONCLUSION: These results give support to the efficacy of CBT in reducing symptoms of ADHD post-intervention. PMID- 27554191 TI - [Amaurosis and contralateral cranial nerve pairs III and VI paralysis after peribulbar block - case report]. AB - BACKGROUND AND OBJECTIVES: Peribulbar anesthesia has emerged as a safer option compared with intraconal retrobulbar block. Still, peribulbar anesthesia may not be considered without risk. Numerous complications have been described when performing this technique. This report aims to describe a rare case of amaurosis and contralateral paralysis while attempting to perform a peribulbar anesthesia. CASE REPORT: Male patient, 75-year old, physical status ASA II, undergoing cataract surgery by phacoemulsification with intraocular lens implantation. Sedated with fentanyl and midazolam and subjected to peribulbar anesthesia. There were no complications during surgery. After finishing the procedure, the patient reported lack of vision in the contralateral eye. Akinesia of the muscles innervated by the cranial nerve pairs III and VI, ptosis, and medium-sized pupils unresponsive to light stimulus were observed. Four hours after anesthesia, complete recovery of vision and eyelid and eyeball movements was seen in the non operated eye. CONCLUSIONS: During peribulbar anesthesia, structures located in the intraconal space can be accidentally hit leading to complications such as described in the above report. Following the technical guidelines and using appropriate size needles may reduce the risk of such complication, but not completely. PMID- 27554192 TI - Near-infrared luminescence and RNA cleavage ability of lanthanide Schiff base complexes derived from N,N'-bis(3-methoxysalicylidene)ethylene-1,2-diamine ligands. AB - A complete series of lanthanide Schiff base salen-type complexes were prepared with trivalent lanthanide ions (Ln3+) and the N,N'-bis-(3 methoxysalicylidene)ethylene-1,2-diamine ligand (Ln3+=La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+, Lu3+). Three unique crystal structures of La3+ and Pr3+N,N'-bis-(3-methoxysalicylidene)ethylene-1,2-diamine complexes, with the La3+ complex prepared in two different synthetic approaches, are reported, namely a dimeric [La(H2L)(NO3)3]2 (H2L=N,N'-bis-(3 methoxysalicylidene)ethylene-1,2-diamine) complex, an asymmetric two-centered [La2(H2L)2(NO3)6] complex and a discrete mononuclear [Pr(H2L)(NO3)2(H2O)2] complex. For Nd3+ and Sm3+, an isotypic mononuclear [Nd(H2L)(NO3)3] and 1D polymeric [Sm(H2L)(NO3)3(MeOH)]n structure was obtained, respectively. The whole series of complexes was tested for their ability to cleave the 20-mer RNA oligonucleotide 5'-AGC-GAU-AAG-AUU-CAU-AUA-UC-3'. Additionally three complexes (Ln3+=Nd3+, Sm3+, Ho3+) were tested for the cleavage of the 12-mer RNA oligonucleotide 5'-GCA-CCC-UGU-CAG-3'. A detailed luminescence study was additionally carried out and revealed that the Eu3+ complex emitted bright red light upon excitation at both 285.8nm and 394.4nm. The Nd3+, Er3+, and Yb3+ complexes showed strong emission in the near-infrared region after excitation at 380nm. PMID- 27554193 TI - TGF-beta1 promotes scar fibroblasts proliferation and transdifferentiation via up regulating MicroRNA-21. AB - TGF-beta1, upregulated in keloid tissue, promotes the proliferation, collagen formation and differentiation of dermal fibroblasts. miR-21 is one of microRNAs first found in human genome. The aim of our study is to explore the mechanisms of miR-21 in TGF-beta1-induced scar fibroblasts proliferation and transdifferentiation. In the present study, first we found that TGF-beta1 promoted scar fibroblasts proliferation and transdifferentiation via up regulating miR-21 expression, which could be attenuated when miR-21 was inhibited. Overexpression of miR-21 had similar effect as TGF-beta1 on proliferation and transdifferentiation. Additionally, TGF-beta1 increased the expressions and activities of MMP2 and MMP9 in keloid fibroblasts, which was suppressed by miR-21 inhibition. Finally, the results demonstrated that PTEN/AKT signaling pathway played important role in TGF-beta1-induced transdifferentiation. In conclusion, our study suggests that TGF-beta1 promotes keloid fibroblasts proliferation and transdifferentiation via up-regulation of miR-21 and PTEN/AKT signalling pathway plays important role in this process, which provides a potential theoretical basis for clinical treatment of skin scars. PMID- 27554195 TI - Factors associated with use of falls risk-increasing drugs among patients of a geriatric oncology outpatient clinic in Australia: a cross-sectional study. AB - Older people with cancer are at increased risk of falling. Falls risk-increasing drugs (FRIDs), comprising psychotropics and medications that cause orthostatic hypotension, are a potentially modifiable risk factor for falls. The objective of this study was to determine the prevalence and factors associated with use of FRIDs in older people with cancer. Patients aged >=70 years who presented to a hospital outpatient clinic between January 2009 and July 2010 were included in the study. Information on current medication use, falls in previous 6 months, and frailty criteria was collected. Multinomial logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CIs) for factors associated with levels of FRID use. Overall, 76.1% (n = 293) of 383 patients used FRIDs. This comprised psychotropics (31.2%, n = 120) and medications causing orthostatic hypotension (69.9%, n = 269). In total, 24.0% (n = 92) patients reported falling in the previous 6 months. Risk factors for falling were associated with use of psychotropics but not orthostatic hypotension drugs. Patients with a history of falls had increased odds of using psychotropics (>=3 psychotropics; OR 13.50; 95%CI, 2.64-68.94). Likewise, frail patients had increased odds of using psychotropics (>=3 psychotropics; OR 27.78; 95%CI, 6.06 127.42). Risk factors for falling were associated with the use of psychotropics. This suggests that clinicians either do not recognize or underestimate the contribution of medications to falls in this high-risk patient group. Further efforts are needed to rationalize medication regimens at the time of patients' first presentation to outpatient oncology services. PMID- 27554194 TI - PAFR activation of NF-kappaB p65 or p105 precursor dictates pro- and anti inflammatory responses during TLR activation in murine macrophages. AB - Platelet-activating factor receptor (PAFR) is a G protein-coupled receptor (GPCR) implicated in many diseases. Toll-like receptors (TLRs) play a critical role in shaping innate and adaptive immune responses. In this study, we investigated whether PAFR signaling changes the macrophages responsiveness to agonists of TLR2 (Pam3Cys), TLR4 (LPS), and TLR3 agonist Poly(I:C). Exogenous PAF inhibited the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-alpha) and increased anti-inflammatory IL-10 in macrophages challenged with Pam3Cys and LPS, but not with Poly (I:C). PAF did not affect mRNA expression of MyD88, suggesting that PAF acts downstream the adaptor. PAF inhibited LPS-induced phosphorylation of NF-kappaB p65 and increased NF-kappaB p105 phosphorylation, which is processed in the proteasome to generate p50 subunit. The PAF potentiation of IL-10 production was dependent on proteasome processing but independent of NF-kappaB transactivation domain. Inhibition of p50 abolished the PAF-induced IL-10 production. These findings indicate that the impaired transcriptional activity of the p65 subunit and the enhanced p105 phosphorylation induced by PAF are responsible for down regulation of pro-inflammatory cytokines and up regulation of IL-10, respectively, in LPS-challenged macrophages. Together, our data unveil a heretofore unrecognized role for PAFR in modulating activation of NF-kappaB in macrophages. PMID- 27554196 TI - First Synthesis of Continuous Mesoporous Copper Films with Uniformly Sized Pores by Electrochemical Soft Templating. AB - Although mesoporous metals have been synthesized by electrochemical methods, the possible compositions have been limited to noble metals (e.g., palladium, platinum, gold) and their alloys. Herein we describe the first fabrication of continuously mesoporous Cu films using polymeric micelles as soft templates to control the growth of Cu under sophisticated electrochemical conditions. Uniformly sized mesopores are evenly distributed over the entire film, and the pore walls are composed of highly crystalized Cu. PMID- 27554197 TI - A randomised controlled trial of cognitive behaviour therapy versus non-directive reflective listening for young people at ultra high risk of developing psychosis: The detection and evaluation of psychological therapy (DEPTh) trial. AB - BACKGROUND: Intervention trials for young people at ultra high risk (UHR) for psychosis have shown cognitive behaviour therapy (CBT) to have promising effects on treating psychotic symptoms but have not focused on functional outcomes. We hypothesized that compared to an active control, CBT would: (i) reduce the likelihood of, and/or delay, transition to psychosis; (ii) reduce symptom severity while improving social functioning and quality of life, whether or not transition occurred. METHOD: This was a single-blind randomised controlled trial for young people at UHR for psychosis comparing CBT to an active control condition, Non Directive Reflective Listening (NDRL), both in addition to standard care, with a 6month treatment phase and 12months of follow-up. Statistical analysis is based on intention-to-treat and used random effect models to estimate treatment effects common to all time-points. RESULTS: Fifty-seven young people (mean age=16.5years) were randomised to CBT (n=30) or NDRL (n=27). Rate of transition to psychosis was 5%; the 3 transitions occurred in the CBT condition (baseline, 2months, 5months respectively). The NDRL condition resulted in a significantly greater reduction in distress associated with psychotic symptoms compared to CBT (treatment effect=36.71, standard error=16.84, p=0.029). There were no significant treatment effects on frequency and intensity of psychotic symptoms, global, social or role functioning. CONCLUSION: Our sample was higher functioning, younger and experiencing lower levels of psychotic like experiences than other trials. The significantly better treatment effect of NDRL on distress associated with psychotic symptoms supports the recommendations for a stepped-care model of service delivery. This treatment approach would accommodate the younger UHR population and facilitate timely intervention. TRIAL REGISTRATION: ANZCTR 12606000101583. PMID- 27554198 TI - Cannabis and a lower BMI in psychosis: What is the role of AKT1? AB - Cannabis use has been associated with favorable outcomes on metabolic risk factors. The cause of this relation is still unknown. In this study we investigated whether this effect is mediated by the AKT1 gene, as activation of the related enzyme by cannabis may cause metabolic changes. Six Single Nucleotide Polymorphisms (SNPs) of the AKT1 gene (rs1130214, rs1130233, rs2494732, rs2498784, rs3730358, and rs3803300) of patients with psychotic disorders (n=623) were related to Body Mass Index (BMI), levels of glycosylated hemoglobin (HBA1c) and total metabolic risk. Next, mediation analysis was performed with BMI as outcome, cannabis as predictor, and AKT1 as mediator. Cannabis use was inversely related to BMI but not with levels of HBA1c and total metabolic risk. Moreover, out of 6 AKT1 SNPs, rs2494732 was associated with cannabis use, but AKT1 did not mediate the effect of cannabis on BMI. In conclusion, cannabis use is likely to be associated with a lower BMI in patients with a psychotic disorder. Moreover, AKT1 risk alleles may increase the incidence of cannabis use in patients with a psychotic disorder, but AKT1 does not appear to mediate the effect of cannabis on BMI. PMID- 27554200 TI - Migratory management and environmental conditions affect lifespan and oxidative stress in honey bees. AB - Most pollination in large-scale agriculture is dependent on managed colonies of a single species, the honey bee Apis mellifera. More than 1 million hives are transported to California each year just to pollinate the almonds, and bees are trucked across the country for various cropping systems. Concerns have been raised about whether such "migratory management" causes bees undue stress; however to date there have been no longer-term studies rigorously addressing whether migratory management is detrimental to bee health. To address this issue, we conducted field experiments comparing bees from commercial and experimental migratory beekeeping operations to those from stationary colonies to quantify effects on lifespan, colony health and productivity, and levels of oxidative damage for individual bees. We detected a significant decrease in lifespan of migratory adult bees relative to stationary bees. We also found that migration affected oxidative stress levels in honey bees, but that food scarcity had an even larger impact; some detrimental effects of migration may be alleviated by a greater abundance of forage. In addition, rearing conditions affect levels of oxidative damage incurred as adults. This is the first comprehensive study on impacts of migratory management on the health and oxidative stress of honey bees. PMID- 27554201 TI - A highly sensitive underwater video system for use in turbid aquaculture ponds. AB - The turbid, low-light waters characteristic of aquaculture ponds have made it difficult or impossible for previous video cameras to provide clear imagery of the ponds' benthic habitat. We developed a highly sensitive, underwater video system (UVS) for this particular application and tested it in shrimp ponds having turbidities typical of those in southern Taiwan. The system's high-quality video stream and images, together with its camera capacity (up to nine cameras), permit in situ observations of shrimp feeding behavior, shrimp size and internal anatomy, and organic matter residues on pond sediments. The UVS can operate continuously and be focused remotely, a convenience to shrimp farmers. The observations possible with the UVS provide aquaculturists with information critical to provision of feed with minimal waste; determining whether the accumulation of organic-matter residues dictates exchange of pond water; and management decisions concerning shrimp health. PMID- 27554199 TI - Increased diffusivity in gray matter in recent onset schizophrenia is associated with clinical symptoms and social cognition. AB - INTRODUCTION: Diffusion weighted MRI (dMRI) is a method sensitive to pathological changes affecting tissue microstructure. Most dMRI studies in schizophrenia, however, have focused solely on white matter. There is a possibility, however, that subtle changes in diffusivity exist in gray matter (GM). Accordingly, we investigated diffusivity in GM in patients with recent onset schizophrenia. METHODS: We enrolled 45 patients and 21 age and sex-matched healthy controls. All subjects were evaluated using the short form of the Wechsler Adult Intelligence Scale, the Positive and Negative Syndrome Scale (PANSS), and the video based social cognition scale. DMRI and T1W images were acquired on a 3 Tesla magnet, and mean Fractional Anisotropy (FA), Trace (TR) and volume were calculated for each of the 68 cortical GM Regions of Interest parcellated using FreeSurfer. RESULTS: There was no significant difference of FA and GM volume between groups after Bonferroni correction. For the dMRI measures, however, patients evinced increased TR in the left bank of the superior temporal sulcus, the right inferior parietal, the right inferior temporal, and the right middle temporal gyri. In addition, higher TR in the right middle temporal gyrus and the right inferior temporal gyrus, respectively, was associated with decreased social function and higher PANSS score in patients with schizophrenia. CONCLUSION: This study demonstrates high sensitivity of dMRI to subtle pathology in GM in recent onset schizophrenia, as well as an association between increased diffusivity in temporal GM regions and abnormalities in social cognition and exacerbation of psychiatric symptoms. PMID- 27554202 TI - Pharmacokinetic/pharmacodynamic studies in the CMI. PMID- 27554203 TI - Ethical considerations in research published in the CMI. PMID- 27554204 TI - A molecular epidemiological perspective of rhinovirus types circulating in Amsterdam from 2007 to 2012. AB - Rhinoviruses (RVs) are frequently detected respiratory viruses that cause mild common cold symptoms, but may also lead to more severe respiratory tract infections. The large number of RV types, classified into species A, B and C, hampers clear insights into the epidemiology and clinical significance of each RV type. The aim of this study was to map the circulation of RV types in the Amsterdam area. RV-positive nasopharyngeal and oropharyngeal samples, collected from 2007 to 2012 in the Academic Medical Centre (Amsterdam, the Netherlands), were typed based on the sequence of the region coding for capsid proteins VP4 and VP2. RV-A, RV-B and RV-C were found in proportions of of 52.4% (334/637), 11.3% (72/637), and 36.2% (231/637), respectively. We detected 129 of the 167 currently classified types. RVs circulated throughout the entire year with a peak in the autumn and a decline in the summer. Some RV types were observed throughout the entire sampling period and others had a more seasonal pattern. Nine RV-A and four RV-B novel provisionally assigned types were identified. This study provides an insight into the molecular epidemiology of RVs in the Amsterdam area. The RVs circulating are diverse and include several provisionally new types. PMID- 27554205 TI - Technical solutions to reduce mediastinal irradiation in young patients undergoing treatment for lymphomas: Preliminary experience. AB - This study aims at optimizing treatment planning in young patients affected by lymphoma (Stage II to III) by using an inclined board (IB) that allows reducing doses to the organs at risk. We evaluated 19 young patients affected by stage I to III lymphomas, referred to our Department for consolidation radiotherapy (RT) treatment on the mediastinum. Patients underwent 2 planning computed tomography (CT) scans performed in different positions: flat standard position and inclined position. A direct comparison between the different treatment plans was carried out analyzing dosimetric parameters obtained from dose-volume histograms generated for each plan. Comparison was performed to evaluate the sparing obtained on breast and heart. Dosimetric evaluation was performed for the following organs at risk (OARs): mammary glands, lungs, and heart. A statistically significant advantage was reported for V5, V20, and V30 for the breast when using the inclined board. A similar result was obtained for V5 and V10 on the heart. No advantage was observed in lung doses. The use of a simple device, such as an inclined board, allows the optimization of treatment plan, especially in young female patients, by ensuring a significant reduction of the dose delivered to breast and heart. PMID- 27554206 TI - Adenoid cystic carcinoma of the urethra/Cowper's gland with concurrent high-grade prostatic adenocarcinoma: a detailed clinicopathologic case report and review of the literature. AB - Primary adenoid cystic carcinoma of the urethra is uncommon with only 9 cases reported in the medical literature; all tumors arose from Cowper's glands. Herein, we report the histological features and immunohistochemical characteristics of 1 patient with primary adenoid cystic carcinoma involving the entire posterior urethra, prostate gland, corpus spongiosum, corpora cavernosa, urogenital diaphragm, perianal soft tissue, and muscularis propria layer of rectum. We also review other published cases to evaluate the prognosis and treatment. PMID- 27554207 TI - Primary lymphoma of bone in the pediatric and young adult population. AB - Primary lymphoma of bone (PLB) accounts for 3% to 7% of primary neoplasms of bone and must be distinguished from more common bone tumors in the pediatric population such as osteosarcoma, Ewing sarcoma, and other small round blue cell tumors. In this study, pathology databases from 4 institutions were queried for PLB in individuals 1 to 21 years old. A total of 54 cases of PLB were identified, including 41 diffuse large B-cell lymphomas (DLBCL, 76%), 8 B-lymphoblastic lymphomas (BLL, 15%), 3 anaplastic large cell lymphomas (ALCL, 6%), and 2 low grade follicular lymphomas (4%). The male/female ratio was 1.8:1 and median age was 16 years (range, 2-21). Patients with DLBCL were significantly older (P<.001), and patients with ALCL and BLL were significantly younger (P=.050 and P=.008, respectively) when compared with the other patients. Due to necrosis, crush artifact, and/or insufficient material, 30% of cases required multiple biopsies for diagnosis. The femur, tibia, pelvic bones, humerus, and vertebrae were most commonly involved. DLBCL patients had significantly more solitary bone involvement (P=.001), whereas BLL had significantly more polyostotic involvement (P<.001). Of the 37 patients with outcome data, all had no evidence of disease on last follow-up. This largest pediatric series of PLB identifies DLBCL as the most frequent subtype and documents rarer occurrences of BLL, ALCL, and follicular lymphomas. The differential diagnosis of bone neoplasms in pediatric patients, including those with necrosis, should include PLB. PMID- 27554208 TI - Longitudinal association of delta activity at sleep onset with cognitive and affective function in community-dwelling older adults. AB - OBJECTIVE: This investigation sought to determine whether delta activity at sleep onset (DASO) in the sleep electroencephalography of older adults represents normal variation or is associated with clinical pathology. To this end, we examined its longitudinal associations with cognitive and affective function in older adults without dementia. METHODS: Participants were 153 community-dwelling older adults without dementia. We evaluated polysomnography (PSG), cognitive performance, and affective function at four time points: baseline, 12, 24, and 36 months. All participants completed PSG and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, visuospatial ability, and measures of anxiety and depression. DASO was defined as sequences of rhythmic anterior delta activity on PSG in the transition from awake to sleep during the baseline assessment (Figure ). RESULTS: At the baseline, 83 women and 70 men, mean age 71.3 +/- 0.6 years participated and 19.6% of participants exhibited DASO. Age, years of education, gender, and body mass index did not differ according to DASO status. Linear mixed modeling showed that the presence of DASO was actually associated with lower levels of anxiety and depression. Further, participants with DASO, versus those without DASO, exhibited a trend towards better cognitive performance over time, although none of these associations reached statistical significance. CONCLUSIONS: Whereas DASO was associated with better affective function, no significant association was found between DASO and cognitive change over time. These longitudinal findings support the view that the presence of DASO in healthy older adults represents normal variation rather than pathological aging. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27554209 TI - Extending the Lifetime of Perovskite Solar Cells using a Perfluorinated Dopant. AB - The principle limitation of perovskite solar cells is related to their instability and, hence, their limited lifetime. Herein, we employ an imidazolium iodide dopant, 1-methyl-3-(1H,1H,2H,2H-nonafluorohexyl)-imidazolium iodide, containing a perfluorous appendage, which leads to prolonged (unencapsulated, under Ar atmosphere) device activities exceeding 100 days without compromising the power conversion efficiency and other photovoltaic parameters. The extended lifetime of the device can be attributed, at least in part, to the hydrophobic nature of the imidazolium iodide salt. The functionalization of the perovskite material was found to have negligible influence on the perovskite crystal structure. PMID- 27554210 TI - Fungal decomposition of terrestrial organic matter accelerated Early Jurassic climate warming. AB - Soils - constituting the largest terrestrial carbon pool - are vulnerable to climatic warming. Currently existing uncertainties regarding carbon fluxes within terrestrial systems can be addressed by studies of past carbon cycle dynamics and related climate change recorded in sedimentary successions. Here we show an example from the Early Jurassic (early Toarcian, c. 183 mya) marginal-marine strata from Poland, tracking the hinterland response to climatic changes through a super-greenhouse event. In contrast to anoxia-related enhanced carbon storage in coeval open marine environments, Total Organic Carbon (TOC) concentrations in the Polish successions are substantially reduced during this event. Increasing temperature favoured fungal-mediated decomposition of plant litter - specifically of normally resistant woody tissues. The associated injection of oxidized organic matter into the atmosphere corresponds to abrupt changes in standing vegetation and may have contributed significantly to the amplified greenhouse climate on Earth. The characteristic Toarcian signature of multiple warm pulses coinciding with rapidly decreasing carbon isotope ratios may in part be the result of a radical reduction of the terrestrial carbon pool as a response to climate change. PMID- 27554211 TI - Quantification of patient-reported outcome measures of radiation-induced skin reactions for use in clinical trial design. AB - PURPOSE: Skin toxicity is a common effect from radiotherapy, although difficult to predict on an individual basis, and there is little evidence-based management. This study aimed to quantify inter-patient variation in patient-reported outcome measures for radiation-induced skin reactions (RISR) to enable the determination of the number of patients required for adequate power in a comparative trial of RISR management strategies. METHODS: The study included 154 patients scheduled to receive breast cancer radiotherapy. Patients filled in a weekly questionnaire during and up to 4 weeks following the end of radiotherapy scoring five aspects of their experience of RISR: skin redness, and bother from redness like itching, burning sensation and tenderness/pain. RESULTS: Assessment of patients' reported experience of their RISR was shown to be feasible, with 91 % of patients returning at least two questionnaires. The mean score increase between weeks 1 and 4 was 25 points (p value <0.0001, 95 % CI 21-29), and the estimated standard deviation at 4 weeks was 18 (95 % CI 16-21). CONCLUSIONS: Patients' assessment of their reaction was not predicted on the basis of treatment and patient-related characteristics. Based on the observed variance in scores at 4 weeks, we could calculate the sample size required for a comparative study of two RISR management policies would be 200 patients to have statistical power to detect a clinically significant difference in patient-rated scores of their skin reactions. A trial employing this tool would help provide an evidence base to guide policy in advising patients how to manage their RISR. PMID- 27554212 TI - [Endoscopic Duodenal Snare Papillectomy Induced Complication: Prevention and Management]. AB - Tumors of the major duodenal papilla are being recognized more often because of the increased use of diagnostic upper endoscopy and ERCP. The standard of management for ampullary tumor is local surgical excision or pancreaticoduodenectomy, but these procedures are associated with significant mortality, as well as post-operative and long-term morbidity. Endoscopic snare papillectomy was introduced as an alternative to surgery, but post-procedure complications are serious drawback. The most serious complications are perforation, delayed bleeding and pancreatitis. Identification of high risk patients, early recognition of complications, and aggressive management abates frequency and severity. Prevention and management of endoscopic duodenal papillectomy-induced complications will be reviewed in this article. PMID- 27554213 TI - Formulation and Management of Poor Bowel Preparation: A Survey Study. AB - BACKGROUND/AIMS: There are no established guidelines for bowel preparation formulation for bowel cleansing, nor is there an optimal method of dealing with inadequate bowel cleansing. This study investigated bowel preparation formulation preferences and responses to bowel preparation situations using surveys. METHODS: The study surveyed 221 Korean lower gastrointestinal endoscopists from January to March 2015 and assessed their responses. RESULTS: The analysis indicated that 2-L polyethylene glycol (PEG) plus ascorbic acid (Asc) was the preferred method (76.5%) and most responders expressed satisfaction with the formulation in both potency and safety. To address poor bowel preparation on the day of colonoscopy, the majority of physicians chose to order ingestion of additional preparations and proceed with the colonoscopy as scheduled (56.6%). In addition, concerns about renal safety and electrolyte stability were raised regarding oral sodium phosphate. CONCLUSIONS: This study found that 2-L PEG+Asc was preferred for potency and safety, and that Korean endoscopists preferred to proceed with colonoscopy in poor bowel preparation situations rather than choose an alternate diagnostic modality. PMID- 27554214 TI - [Optimal Operational Definition of Patient with Peptic Ulcer Bleeding for Big Data Analysis Using Combination of Clinical Characteristics in a Secondary General Hospital]. AB - BACKGROUND/AIMS: Peptic ulcer bleeding (PUB) is the most common cause of upper gastrointestinal bleeding in Korea but there has been no research done using big data. This study evaluates the optimal operational definition (OD) for big data research by analyzing clinical characteristics of PUB. METHODS: We reviewed the clinical characteristics of 92 patients with PUB confirmed on endoscopy in Wonkwang University Sanbon Hospital (January 2013 to December 2014). We calculated sensitivity and positive predictive value (PPV) to detect confirmed PUB patients using ODs developed by combining clinical features of patients with PUB. RESULTS: The mean patient age was 63 years. Men had higher prevalence of PUB than women. Bleeding gastric ulcer was proportionately common in the age range of 40s to 60s in men, while a significantly higher rate of bleeding occurred in women older than 70s. The rate of drug-induced ulcer was 28.2%, whereas the prevalence of Helicobacter pylori was 47.8%. Among the hospitalized patients with diagnostic code of PUB, we ruled out patients with endoscopic removal of gastric adenoma or peritonitis, and selected patients who had been administered intravenous proton pump inhibitor. The sensitivity in this setting was 82.6%, and PPV was 88.4%. CONCLUSIONS: PUB was more common in older patients, and there was a clear gender difference in gastric ulcer bleeding by age. With a proper OD using PUB diagnostic codes, we can identify true patients with sufficiently high sensitivity and PPV. PMID- 27554215 TI - Rare Case of Primary Gastric Burkitt Lymphoma in a Child. AB - Primary gastric tumors are very rare in children. Burkitt lymphoma is a common type of non-Hodgkin's lymphoma, and gastric Burkitt lymphoma usually occurs in the aged. When involving the gastrointestinal tract, primary gastric Burkitt lymphoma is very rare in younger childhood. Many gastric lymphomas including mucosa-associated lymphoid tissue lymphoma are associated with Helicobacter pylori infection or acute bleeding symptom. We report a seven-year-old boy who presented with only some vomiting and postprandial pain. His upper gastrointestinal endoscopy and biopsy revealed a large primary Burkitt lymphoma with no acute bleeding and no evidence of H. pylori infection. After chemotherapy, he remains in remission. PMID- 27554216 TI - [A Case of Isolated Leptomeningeal Carcinomatosis from Advanced Gastric Cancer]. AB - Leptomeningeal carcinomatosis (LMC) is rare metastatic form of gastric cancer. Most cases are diagnosed in the final stage after multiple distant metastasis. An 84-year-old woman was admitted with melena, headache and vomiting. Esophagogastroduodenoscopy showed an ulceroinfiltrating lesion at the stomach (Borrmann class III), and biopsy revealed a signet ring cell carcinoma. The abdominal-pelvic CT showed no evidence of metastasis. A sudden decrease of consciousness was noted, but the brain CT showed no active lesion while the brain MRI revealed enhancement of leptomeninges. A lumbar puncture was performed and the cerebrospinal fluid study revealed malignant neoplastic cells. With family consent, no further evaluation and treatment were administered and she died six weeks after the diagnosis of gastric cancer. We report an extremely rare case of a patient who initially presented with neurologic symptoms, and was diagnosed LMC from advanced gastric cancer without any evidence of metastasis in abdomen and pelvis. PMID- 27554217 TI - [Gastric Mucormycosis Followed by Traumatic Cardiac Rupture in an Immunocompetent Patient]. AB - Gastric mucormycosis is a rare and life-threatening fungal disease, caused by fungus in the order Mucorales. While rhino-cerebral and pulmonary forms are common, gastric mucormycosis is an uncommon site for the disease. We diagnosed gastric mucormycosis in a 41-year-old female who had severe multiple trauma, including cardiac rupture, due to a traffic accident. Eighteen days after hospitalization, she passed 800 mL of melena over one day. We performed upper esophagogastroduodenoscopy (EGD) and found a huge gastric ulcer with bleeding. Histopathological examination identified non-septated and right-angled branching fungal hyphae, and we diagnosed gastric mucormycosis. We recommended total gastrectomy to her but she refused the operation, so she was treated with liposomal amphotericin B for 53 days. After two months of treatment with liposomal amphotericin B, we again performed EGD and found a healed gastric ulcer. After four months, with another EGD, we found that the gastric mucormycosis was completely healed. PMID- 27554218 TI - A Case of Ulcerative Colitis Following Acute Hepatitis Induced by Epstein-Barr Virus Infection. AB - Epstein-Barr virus (EBV) infection varies in its clinical manifestations and severity. EBV can be a causative agent of hepatitis and may have a role in the pathogenesis of chronic autoimmune diseases including inflammatory bowel disease. A 24-year-old woman was admitted to our hospital, presenting with fever and elevated liver enzymes. She was diagnosed with acute hepatitis and EBV infection according to serologic tests and liver biopsy. Within two months, she was re admitted to our hospital, presenting with hematochezia and lower abdominal pain. She was diagnosed with ulcerative colitis. In situ hybridization for EBV was positive in initial liver biopsy and colon biopsy. Here we report an unusual case of acute EBV hepatitis followed at a short interval by ulcerative colitis. PMID- 27554219 TI - [A Case of Composite Hepatocellular Carcinoma and Neuroendocrine Carcinoma in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis B]. AB - Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis. PMID- 27554220 TI - [Primary Biliary Mucosa-associated Lymphoid Tissue Lymphoma Mimicking Hilar Cholangiocarcinoma]. AB - Primary biliary mucosa-associated lymphoid tissue (MALT) lymphoma is extremely rare. We report a case of primary biliary MALT lymphoma with obstructive jaundice diagnosed by endoscopic biopsy, without surgical intervention. Obstructive jaundice was relieved by endoscopic drainage and endoscopic biopsy was done simultaneously during endoscopic retrograde cholangiopancreatography. Unnecessary surgical intervention can be avoided after pathological confirmation of lymphoma. The patient received radiotherapy, and is alive without any evidence of recurrence or biliary obstruction. Diagnosis of primary biliary lymphoma is very difficult because of its low prevalence. However, it should always be considered as a differential diagnosis, since when an accurate diagnosis is made, unnecessary surgical intervention can be avoided. PMID- 27554221 TI - Timing of Extubation After Cardiac Surgery. PMID- 27554222 TI - Preoperative Electrocardiogram Score for Predicting New-Onset Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery. AB - OBJECTIVE: To investigate if electrocardiogram (ECG) markers from routine preoperative ECGs can be used in combination with clinical data to predict new onset postoperative atrial fibrillation (POAF) following cardiac surgery. DESIGN: Retrospective observational case-control study. SETTING: Single-center university hospital. PARTICIPANTS: One hundred consecutive adult patients (50 POAF, 50 without POAF) who underwent coronary artery bypass grafting, valve surgery, or combinations. INTERVENTIONS: Retrospective review of medical records and registration of POAF. MEASUREMENTS AND MAIN RESULTS: Clinical data and demographics were retrieved from the Western Denmark Heart Registry and patient records. Paper tracings of preoperative ECGs were collected from patient records, and ECG measurements were read by two independent readers blinded to outcome. A subset of four clinical variables (age, gender, body mass index, and type of surgery) were selected to form a multivariate clinical prediction model for POAF and five ECG variables (QRS duration, PR interval, P-wave duration, left atrial enlargement, and left ventricular hypertrophy) were used in a multivariate ECG model. Adding ECG variables to the clinical prediction model significantly improved the area under the receiver operating characteristic curve from 0.54 to 0.67 (with cross-validation). The best predictive model for POAF was a combined clinical and ECG model with the following four variables: age, PR-interval, QRS duration, and left atrial enlargement. CONCLUSION: ECG markers obtained from a routine preoperative ECG may be helpful in predicting new-onset POAF in patients undergoing cardiac surgery. PMID- 27554223 TI - Cardiac Hydatid Disease: An Uncommon Cause of Cardiac Tumors. PMID- 27554224 TI - Paradoxical Tumor Embolism and Recurrent Intracardiac Mass From Uterine Intravenous Leiomyomatosis. PMID- 27554225 TI - Clinical Significance of Acquired Left Atrial Shadow. PMID- 27554226 TI - 3D Printing for Simulation in Thoracic Anesthesia. PMID- 27554227 TI - Effect of Continuous Paravertebral Dexmedetomidine Administration on Intraoperative Anesthetic Drug Requirement and Post-Thoracotomy Pain Syndrome After Thoracotomy: A Randomized Controlled Trial. AB - OBJECTIVES: To assess the effect of paravertebral administration of dexmedetomidine as an adjuvant to local anesthetic on the intraoperative anesthetic drug requirement and incidence of post-thoracotomy pain syndrome. DESIGN: Prospective, randomized, controlled, double-blind trial. SETTING: Single university hospital. PARTICIPANTS: The study comprised 30 patients who underwent elective thoracotomy and were assigned randomly to either the Ropin or Dexem group (n = 15 each). INTERVENTIONS: All patients received the study medications through paravertebral catheter. Patients in the Ropin group received a bolus of 15 mL of 0.75% ropivacaine over 3-to-5 minutes followed by an infusion of 0.2% ropivacaine at 0.1 mL/kg/hour. Patients in the Dexem group received 15 mL of 0.75% ropivacaine plus dexmedetomidine, 1 ug/kg bolus over 3-to-5 minutes followed by an infusion of 0.2% ropivacaine plus 0.2 ug/kg/hour of dexmedetomidine at 0.1 mL/kg/hour. MEASUREMENTS AND MAIN RESULTS: The primary outcome of the study was intraoperative anesthetic drug requirement. The secondary outcome was the incidence of post-thoracotomy pain syndrome 2 months after surgery. The amount of propofol required for induction of anesthesia was significantly less in the Dexem group (Dexem 49.33+/-20.51 v 74.33+/-18.40 in the Ropin group, p = 0.002). End-tidal isoflurane needed to maintain target entropy was significantly less in the Dexem group at all time points. Intraoperative fentanyl requirement was lower in the Dexem group (Dexem 115.33+/-33.77 v 178.67+/-32.48 in the Ropin group, p = 0.002). Postoperative pain scores and morphine consumption were significantly less in the Dexem group (p<0.001). The incidence of post-thoracotomy pain syndrome was comparable between the 2 groups (69.23% v 50%, p = 0.496). CONCLUSIONS: Paravertebral dexmedetomidine administration resulted in decreased intraoperative anesthetic drug requirement, less pain, and lower requirements of supplemental opioid in the postoperative period. However, it had no effect on the incidence of post-thoracotomy pain syndrome. PMID- 27554228 TI - Know the Guard of Coronary Sinus Before Cannulation. PMID- 27554229 TI - Colloids Versus Crystalloids: Is That the Real Problem? PMID- 27554230 TI - Smoking Cessation Can Reduce the Incidence of Postoperative Hypoxemia After On Pump Coronary Artery Bypass Grafting Surgery. AB - OBJECTIVES: To determine whether smoking cessation can reduce the incidence of postoperative hypoxemia (POH) after on-pump coronary artery bypass grafting (CABG) surgery. DESIGN: Prospective, single-center, observational study. SETTING: Single-center university teaching hospital. PARTICIPANTS: The study comprised 300 patients undergoing on-pump CABG surgery who met the inclusion criteria. Patients were divided into the following 3 groups according to smoking status: sustained quitters (n = 132)-smoking cessation for more than 1 month and less than 1 year; quitters (n = 95)-smoking cessation for more than 1 week and less than 1 month; and smokers (n = 73)-smoking at least 1 cigarette per day for at least 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of POH after on-pump CABG surgery. Secondary outcomes included length of postoperative mechanical ventilation and intensive care unit stay between the POH group and non-POH group. There were significant decreases of POH incidence in the sustained quitters and quitters compared with the smokers both after intensive care unit (ICU) admission and 24 hours after surgery (18.2%, 18.9%, v 32.9%; p = 0.036 and 9.8%, 10.5%, v 26%; p = 0.003, respectively), and there was no significant difference in POH incidence between the sustained quitters and quitters. The length of postoperative mechanical ventilation was longer in smokers than in sustained quitters and quitters (15.9+/-6.1 h v 11.9+/-5.3 h and 13.0+/-5.8 h, respectively; p<0.05), but there were no significant differences in the length of ICU stay among the 3 groups (54.2+/-7.5 h v 55.1+/-7.5 h and 53.7+/ 6.6 h, respectively; p = 0.333). CONCLUSIONS: Smoking cessation can reduce POH after on-pump CABG surgery, and it also can shorten the length of postoperative mechanical ventilation. PMID- 27554231 TI - Left Pulmonary Artery Stent Causes Ipsilateral Pulmonary Complication. PMID- 27554232 TI - Reply to Wolvetang et al: "Serotonin Syndrome After Methylene Blue Administration During Cardiac Surgery: A Case Report and Review". PMID- 27554233 TI - A Rare Cause of Exercise Intolerance and Progressive Dyspnea in an Elderly Woman. PMID- 27554234 TI - Continuous Monitoring of Lactate Using Intravascular Microdialysis in High-Risk Cardiac Surgery: A Prospective Observational Study. AB - OBJECTIVE: To assess the accuracy and applicability of a novel system, not requiring calibration, for continuous lactate monitoring with intravascular microdialysis in high-risk cardiac surgery. DESIGN: Single-center prospective observational study. SETTING: City Hospital #1 of Arkhangelsk, Russian Federation. PARTICIPANTS: Twenty-one adult patients undergoing elective complex repair or replacement of two or more valves or combined valve and coronary artery cardiac surgery. INTERVENTIONS: After induction of anesthesia, in all patients a dedicated triple-lumen catheter functioning as a regular central venous catheter with integrated microdialysis function was inserted via the right jugular vein for continuous lactate monitoring using the intravascular microdialysis system. MEASUREMENTS AND MAIN RESULTS: Lactate values displayed by the microdialysis system were compared with the reference arterial blood gas (ABG) values. In total, 432 paired microdialysis-ABG lactate samples were obtained. After surgery, the concentration of lactate increased significantly, peaking at 8 hours (p<0.05). The lactate clearance within 8 hours after peak concentration was 50% (39%-63%). There was a significant correlation between Lactatecont and Lactatecont (rho = 0.92, p<0.0001). Bland-Altman analysis showed a bias (mean difference)+/-limits of agreement (+/-1.96 SD) of 0.09+/-1.1 mmol/L. In patients with postoperative complications, peak lactate concentration was significantly higher compared with those without complications: 6.75 (4.43-7.75) mmol/L, versus 4.20 (3.95-4.87) mmol/L (p = 0.002). CONCLUSIONS: Lactate concentration increased significantly after high-risk cardiac surgery. The intravascular microdialysis technique for lactate measurement provided acceptable accuracy and can be used for continuous blood lactate monitoring in cardiac surgery. PMID- 27554235 TI - PAUSE: Perioperative Bedside Ultrasound. PMID- 27554236 TI - High Postoperative Blood Pressure After Cardiac Surgery Is Associated With Acute Kidney Injury and Death. AB - OBJECTIVES: Gaps and uncertainty exist regarding the understanding of optimal clinical goals for perioperative (ie, preoperative, intraoperative, and postoperative) blood pressure (BP) management in patients undergoing cardiac surgery and the consequences of achieving or failing to achieve those goals. In this setting, it is understood that preoperative hypertension is predictive of poor postoperative outcomes, with a growing appreciation that current, clinically acceptable changes in intraoperative BP also may be associated independently with adverse short- and long-term outcomes. In contrast, the impact of postoperative BP on outcomes after cardiac surgery remains less clear. DESIGN: This study was a retrospective outcome analysis. SETTING: The study included all cardiac surgery patients cared for at a single institution over a 7-year period. Consequences of the success or failure of meeting postoperative BP targets on medical outcomes and health resource utilization were evaluated. RESULTS: The study comprised 5,225 patients. Hypertensive postoperative patients experienced a higher in hospital mortality rate compared with matched-case normotensive patients (4.97% v 1.32%, p<0.001) and a longer hospital stay (p = 0.024). In hypertensive patients, serum creatinine levels from postoperative day 1 through postoperative day 7 were increased compared with baseline and postoperative renal dysfunction according to the Kidney Disease: Improving Global Outcomes criteria occurred significantly more often (25.3% v 19.7%, p = 0.027). CONCLUSIONS: Postoperative hypertension is associated with compromised outcome as reflected by higher mortality, longer length of stay, and higher incidence of renal dysfunction. PMID- 27554237 TI - Etomidate and the Risk of Complications After Cardiac Surgery: A Retrospective Cohort Analysis. AB - OBJECTIVE: To compare incidence of atrial arrhythmia, duration of care, and major complications after cardiac surgery between patients who received etomidate and those who received other induction agents. DESIGN: Retrospective cohort study utilizing propensity score matching. SETTING: A single academic, tertiary care hospital. PARTICIPANTS: Eight thousand nine hundred seventy-eight patients undergoing coronary artery bypass grafting (CABG), valve, or combined valve/CABG surgery requiring cardiopulmonary bypass between January 2005 and December 2010. INTERVENTIONS: Patients were divided into those who received etomidate at anesthetic induction and those who received another induction agent. Patients given etomidate were propensity-score matched to patients given other induction agents in a 2:1 ratio. MEASUREMENTS AND MAIN RESULTS: Of 8,978 patients who underwent CABG, valve, or combined valve/surgery, 6,313 received etomidate and 2,665 received other induction agents. Among these, the authors successfully matched 4,094 etomidate patients with 2,524 non-etomidate patients. The authors did not find a significant association between receiving etomidate and odds of experiencing postoperative atrial arrhythmia (odds ratio [98.3% confidence interval] of 1.07 [0.92, 1.23], p = 0.29). Etomidate was not associated significantly with either intensive care unit or hospital stay. Etomidate was associated significantly with use of packed red blood cells (odds ratio [99.6% confidence interval] of 1.32 [1.02, 1.70], p = 0.002), but not with use of fresh frozen plasma, platelets, or cryoprecipitate. None of the other complications differed significantly between the groups. CONCLUSIONS: Etomidate was not associated with increased incidence of postoperative atrial arrhythmia or increased intensive care unit or hospital stay. PMID- 27554238 TI - Erratum to 'Independent Risk Factors for Fast-Track Failure Using a Predefined Fast-Track Protocol in Preselected Cardiac Surgery Patients' [Journal of Cardiothoracic and Vascular Anesthesia 29 (2015) 1461-1465]. PMID- 27554239 TI - The gut-skin axis in health and disease: A paradigm with therapeutic implications. AB - As crucial interface organs gut and skin have much in common. Therefore it is unsurprising that several gut pathologies have skin co-morbidities. Nevertheless, the reason for this remains ill explored, and neither mainstream gastroenterology nor dermatology research have systematically investigated the 'gut-skin axis'. Here, in reviewing the field, we propose several mechanistic levels on which gut and skin may interact under physiological and pathological circumstances. We focus on the gut microbiota, with its huge metabolic capacity, and the role of dietary components as potential principle actors along the gut-skin axis. We suggest that metabolites from either the diet or the microbiota are skin accessible. After defining open key questions around the nature of these metabolites, how they are sensed, and which cutaneous changes they can induce, we propose that understanding of these pathways will lead to novel therapeutic strategies based on targeting one organ to improve the health of the other. PMID- 27554240 TI - Atomic and Ionic Radii of Elements 1-96. AB - Atomic and cationic radii have been calculated for the first 96 elements, together with selected anionic radii. The metric adopted is the average distance from the nucleus where the electron density falls to 0.001 electrons per bohr(3) , following earlier work by Boyd. Our radii are derived using relativistic all electron density functional theory calculations, close to the basis set limit. They offer a systematic quantitative measure of the sizes of non-interacting atoms, commonly invoked in the rationalization of chemical bonding, structure, and different properties. Remarkably, the atomic radii as defined in this way correlate well with van der Waals radii derived from crystal structures. A rationalization for trends and exceptions in those correlations is provided. PMID- 27554241 TI - Identification of protein binding partners of small molecules using label-free methods. AB - INTRODUCTION: Drug discovery efforts across the globe are chasing new drug targets and novel mechanisms of action. To support the identification of novel mechanisms of action, phenotype-based drug screening has significantly increased over the last decade. Along with the rise in phenotypic screening, methods and technologies that can help to identify drug targets of phenotypically screened 'hits' have also evolved significantly. AREAS COVERED: This article provides an overview of successful examples, limitations and advances in small-molecule target identification methodologies. Primarily, the methods are described, where small-molecules without derivatization are used as test-molecules for identifying their direct binding protein partners, the targets, in detail. A brief discussion of other affinity chromatography coupled mass-spectrometry based target identification methods are also presented for comparative appreciation of label free methods. EXPERT OPINION: Label-free methods do not require (a) extensive structure activity analysis of phenotypically screened 'hits' and (b) preparation of tool compounds or target capturing probes for target identification. These methods are significantly shortening the time required for the identification and the downstream validation of targets and hence are gaining popularity as the method of choice for target identification. PMID- 27554242 TI - Disrupting the Status Quo in Prostate Cancer Diagnosis. PMID- 27554243 TI - Re: 225Ac-PSMA-617 for PSMA-Targeting Alpha-radiation Therapy of Patients with Metastatic Castration-resistant Prostate Cancer. PMID- 27554245 TI - Termination of the left atrial tachycardia by the ablation of epicardial critical isthmus visualized with a novel high-resolution mapping system. PMID- 27554246 TI - Corrigendum to "Peripheral nerve tumors associated with Martin-Gruber anastomosis" [Clin. Neurophysiol. 126 (2015) 428-430]. PMID- 27554244 TI - Personalized absolute benefit of statin treatment for primary or secondary prevention of vascular disease in individual elderly patients. AB - OBJECTIVE: To estimate the absolute treatment effect of statin therapy on major adverse cardiovascular events (MACE; myocardial infarction, stroke and vascular death) for the individual patient aged >=70 years. METHODS: Prediction models for MACE were derived in patients aged >=70 years with (n = 2550) and without (n = 3253) vascular disease from the "PROspective Study of Pravastatin in Elderly at Risk" (PROSPER) trial and validated in the "Secondary Manifestations of ARTerial disease" (SMART) cohort study (n = 1442) and the "Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm" (ASCOT-LLA) trial (n = 1893), respectively, using competing risk analysis. Prespecified predictors were various clinical characteristics including statin treatment. Individual absolute risk reductions (ARRs) for MACE in 5 and 10 years were estimated by subtracting on-treatment from off-treatment risk. RESULTS: Individual ARRs were higher in elderly patients with vascular disease [5-year ARRs: median 5.1 %, interquartile range (IQR) 4.0-6.2 %, 10-year ARRs: median 7.8 %, IQR 6.8-8.6 %] than in patients without vascular disease (5-year ARRs: median 1.7 %, IQR 1.3-2.1 %, 10-year ARRs: 2.9 %, IQR 2.3 3.6 %). Ninety-eight percent of patients with vascular disease had a 5-year ARR >=2.0 %, compared to 31 % of patients without vascular disease. CONCLUSIONS: With a multivariable prediction model the absolute treatment effect of a statin on MACE for individual elderly patients with and without vascular disease can be quantified. Because of high ARRs, treating all patients is more beneficial than prediction-based treatment for secondary prevention of MACE. For primary prevention of MACE, the prediction model can be used to identify those patients who benefit meaningfully from statin therapy. PMID- 27554247 TI - Lower muscle density is associated with major postoperative complications in older patients after surgery for colorectal cancer. AB - BACKGROUND: Reduced muscle density is associated with an increased risk of postoperative complications. We examined the prognostic value of muscle density as a predictor of postoperative complications in elderly patients undergoing surgery for colorectal cancer. METHODS: Patients (>=70 years) who underwent surgery for colorectal cancer between 2006 and 2013 were selected from a prospective single centre database. The Hounsfield Unit Average (HUA or HU/mm2) of the psoas muscles at the level of the third lumbar vertebra was calculated on the scan. High and low muscle density groups were identified based on the lowest gender specific HUAC quartile. Major postoperative complications (Clavien-Dindo (CD) >=3) within 30 days after surgery were retrospectively documented. Logistic regression analysis was used to identify risk factors for postoperative complications. RESULTS: A total of 373 patients (median age = 78 years) were included in this study. The mean muscle density score was 24.5 +/- 4.3 HU/mm2 for males and 26.3 +/- 5.0 HU/mm2 for females. The cut-off point for the lowest gender specific quartile was <=22.0 HU/mm2 for males and <=23.5 HU/mm2 for females. After multivariable regression, there was a statistically significant association between muscle density and CD >= 3 (OR = 1.84 (95% CI 1.11-3.06), p = 0.019). Anastomotic leakage in patients with a primary anastomosis (n = 287) occurred more often in patients with low muscle density (11.7% vs 23.3%, p = 0.016). The associations remained significant after correction for confounders. CONCLUSION: Low muscle density is associated with major postoperative complications in older patients who undergo surgery for colorectal cancer. PMID- 27554248 TI - Focus on research: Nodal dissection for gastric cancer - A dilemma worthy of King Solomon! PMID- 27554249 TI - Impact of laminar air flow on operating room contamination, and surgical wound infection rates in clean and contaminated surgery. PMID- 27554250 TI - Enhanced recovery after surgery for gastric cancer and an assessment of preoperative carbohydrate loading. AB - BACKGROUND: We previously reported on the feasibility of enhanced recovery after surgery (ERAS) protocol for gastric cancer with a prospective phase II study, but the superiority of this approach over non-ERAS perioperative management remains unclear. Preoperative carbohydrate loading, an important element of the ERAS protocol, has been shown to reduce insulin resistance, but its effects on clinical endpoints in gastric cancer surgery remain controversial. The aim of this study was to clarify the efficacy of the ERAS protocol for gastric cancer surgery, with particular focus on preoperative carbohydrate loading. METHODS: In this ERAS case-control study, we enrolled 121 patients as a case group and 259 patients undergoing gastrectomy for gastric cancer with our conventional perioperative management as a control group. Matched-pair analysis was performed to balance the patients' characteristics for comparison analysis. RESULTS: After matching, 108 patients were included in each group. Postoperative hospital stay was significantly shorter in the ERAS group than in the control group (8 days vs. 9 days, p < 0.001), while the incidence of Clavien-Dindo classification grade II or more postoperative complication was similar between the groups (11.1% vs. 15.7%, p = 0.325). No significant differences were found in serum albumin level, body weight, or grip strength between the groups before surgery and at 1 week and 1 month after surgery. CONCLUSION: Use of the ERAS protocol for gastric cancer shortened the length of postoperative hospital stay without increasing complications. Preoperative carbohydrate loading didn't improve the postoperative nutritional status or maintain the muscle strength postoperatively. PMID- 27554251 TI - Methods for assessing the reliability of quality of life based on SF-36. AB - The 36-Item Short Form Health Survey (SF-36) has been widely used to measure quality of life. Reliability has been traditionally assessed by intraclass correlation coefficient (ICC), which is equivalent to Cronbach's alpha theoretically. However, it is a scaled assessment of reliability and does not indicate the extent of differences because of measurement error. In this paper, total deviation index (TDI) is used to interpret the magnitude of measurement error for SF-36, and a new formula for computing TDI for average item score is proposed. The interpretation based on TDI is simple and intuitive by providing, with a high probability, the expected difference that is because of measurement error. We also show that a high value of ICC does not always correspond to a smaller magnitude of measurement error, which indicates that ICC can sometimes provide a false sense of high reliability. The methodology is illustrated with reported SF-36 data from the literature and from real data in the Arthritis Self Management Program. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27554252 TI - Mianserin affects alarm reaction to conspecific chemical alarm cues in Nile tilapia. AB - In this study, I show that mianserin, a chemical with serotonin and adrenoceptor antagonist activities, increases fish vulnerability to a potential predator threat, when prey fish must deal with this threat based on conspecific chemical alarm cues. For that, I evaluated whether mianserin, diluted in the water, influences the behavioral responses of Nile tilapia (Oreochromis niloticus) to conspecific skin extract (chemical alarm cues). I found that, while mianserin did not abolished antipredator responses, this drug mitigates some components of this defensive reaction. Thus, a potential decrease in serotonin and adrenergic activities reduces the ability of dealing with predators when perceiving conspecific chemical alarm cues. PMID- 27554253 TI - Variability of Myocardial Repolarization in Pediatric Patients with a Ventricular Septal Defect. AB - : In patients with a ventricular septal defect, left-to-right shunting increases the left ventricular preload. This pathological change affects myocardial depolarization and repolarization and has the potential to evoke arrhythmogenic substrates. We examined the effect of ventricular septal defects on myocardial repolarization by investigating the variability in the repolarization interval. This retrospective study included 19 patients (mean age, 1.8 +/- 2.1 years) who underwent surgical closure (mean left-to-right shunt ratio, 2.60 +/- 0.55) and 26 age-matched healthy controls from 2008 to 2015. Using preoperative electrocardiograms, we studied two electrocardiographic parameters (heart rate corrected repolarization and variability of repolarization) and four repolarization intervals (QT, JT, J point to T peak [JTp], and T peak to T end [Tp-e] intervals). The variability index (VI) was calculated from the logarithm of the ratio of the repolarization parameter variance to heart rate variance. The various measures were compared between the patients and controls, and significant differences were found in the corrected QT, JTp, and Tp-e intervals (p < 0.05). The VI of the four intervals also showed significant differences (patients vs. CONTROLS: QTVI, -0.55 +/- 0.61 vs. -1.10 +/- 0.53; JTVI, -0.33 +/- 0.60 vs. -0.86 +/- 0.57; JTpVI, -0.15 +/- 0.78 vs. -0.73 +/- 0.56; Tp-eVI, 0.75 +/- 0.70 vs. 0.11 +/- 0.73, respectively; p < 0.05). No correlation was found between the QTVI and corrected QT interval using linear regression analysis. These repolarization characteristics provide not only electrophysiological indices but also a new index with which to assess the pathophysiology of congenital heart disease. PMID- 27554254 TI - Cardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies. AB - RASopathies are a group of syndromes caused by germline mutations of the RAS/MAPK pathway. They include Noonan syndrome, cardio-facio-cutaneous syndrome, Costello syndrome, and Noonan syndrome with multiple lentigines, which share many characteristic features including cardiac abnormalities. Here, we retrospectively reviewed the clinical manifestations and evaluated the genotype-phenotype associations with special focus on cardiac lesions of the patients with RASopathies. Cardiac symptoms were the most common initial presentation (27 %), except for admission to neonatal intensive care. Although there was a significant gap between the first visit to the hospital and the diagnosis of the genetic syndrome (19.9 +/- 39.1 months), the age at the clinical diagnosis of the genetic syndrome was significantly lower in patients with CHD than in patients without CHD (47.26 +/- 67.42 vs. 86.17 +/- 85.66 months, p = 0.005). A wide spectrum of cardiac lesions was detected in 76.1 % (118/155) of included patients. The most common lesion was pulmonary stenosis, followed by atrial septal defect and hypertrophic cardiomyopathy (HCMP). About half of the pulmonary stenosis and HCMP patients progressed during the median follow-up period of 109.9 (range 9.7-315.4) months. Early rapid aggravation of cardiac lesions was linked to poor prognosis. MEK1, KRAS, and SOS1 mutations tend to be highly associated with pulmonary stenosis. Cardiologists may play important roles in early detection and diagnosis of RASopathies as well as associated CHDs. Due to the variety of clinical presentations and their progression of severity, proper management with regular long-term follow-up of these patients is essential. PMID- 27554255 TI - Home Monitoring Program Reduces Mortality in High-Risk Sociodemographic Single Ventricle Patients. AB - A clinician-driven home monitoring program can improve interstage outcomes in single-ventricle patients. Sociodemographic factors have been independently associated with mortality in interstage patients. We hypothesized that even in a population with high-risk sociodemographic characteristics, a home monitoring program is effective in reducing interstage mortality. We defined interstage period as the time period between discharge following Norwood palliation and second-stage surgery. We reviewed the charts of patients for the three-year period before (group 1) and after (group 2) implementation of the home monitoring program. Clinical variables around Norwood palliation, during the interstage period, and at the time of second-stage surgery were analyzed. There were 74 patients in group 1 and 52 in group 2. 59 % patients were Hispanic, and 84 % lived in neighborhoods where over 5 % families lived below poverty line. There was no significant difference in pre-Norwood variables, Norwood discharge variables, age at second surgery, or outcomes at second surgery. There were more Sano shunts performed at the Norwood procedure as the source of pulmonary blood flow in group 2 (p value <0.05). There were more unplanned hospital admissions and percutaneous re-interventions in group 2. Patients in group 2 whose admission criteria included desaturation had a 45 % likelihood of having an unplanned re intervention. Group 2 noted an 80 % relative reduction in interstage mortality (p < 0.01). In a multiple regression analysis, after accounting for ethnicity, socio economic status, and source of pulmonary blood flow, enrollment in a home monitoring program independently predicted improved interstage survival (p < 0.01). A clinician-driven home monitoring program reduces interstage mortality even when the majority of patients has high-risk sociodemographic characteristics. PMID- 27554256 TI - Variable Myocardial Response to Load Stresses in Infants with Single Left Ventricular Anatomy: Influence of Initial Physiology and Surgical Palliative Strategy. AB - Initial surgical strategies in neonates with single left ventricular (LV) anatomy vary based on adequacy of pulmonary and systemic blood flow. Differing myocardial responses to these strategies, as reflected in indices of systolic function, ventricular size, and mass have not been well defined. We sought to evaluate single LV myocardial response to varied physiology and initial palliation and determine whether the response is consistent and predictable. Infants with single LV physiology were divided based on neonatal palliation: no palliation/PA band (NO); BT shunt only (BT); or Norwood procedure (NP). Echo measures were obtained at presentation, early post-bidirectional Glenn (BDG), late post-BDG follow-up, and post-Fontan procedure. Measures included ejection fraction, LV mass indexed to height2.7 and end diastolic volume indexed to body surface area, and mass/volume ratio. The cohort included 38 children (13 NO, 13 BT, 12 NP). Ejection fraction was similar but depressed in all groups at all stages. LV mass was higher in the NP group than the BT group at early post-BDG (p = 0.03) and higher than both BT and NO groups (p < 0.01) at late post-BDG, but the difference was resolved by post-Fontan follow-up. The NP group had the most remarkable remodeling in LV size from BDG to Fontan, suggesting that volume unloading is most valuable in this subgroup. Ventricular remodeling can be identified by echocardiography in children with single LV physiology, despite variable initial surgical palliative strategies. Importantly, these initial surgical strategies do not result in significant differences after Fontan palliation during early childhood. PMID- 27554259 TI - 2nd European Summer School on Nutrigenomics. September 5-9, 2016, Camerino, Italy: Abstracts. PMID- 27554258 TI - Current management and hospital outcome of the acute coronary syndromes. PMID- 27554257 TI - Androgenetic Alopecia: An Update of Treatment Options. AB - Androgenetic alopecia (AGA) is characterized by a non-scarring progressive miniaturization of the hair follicle in predisposed men and women with a pattern distribution. Although AGA is a very prevalent condition, approved therapeutic options are limited. This article discusses the current treatment alternatives including their efficacy, safety profile, and quality of evidence. Finasteride and minoxidil for male androgenetic alopecia and minoxidil for female androgenetic alopecia still are the therapeutic options with the highest level evidence. The role of antiandrogens for female patients, the importance of adjuvant therapies, as well as new drugs and procedures are also addressed. PMID- 27554260 TI - Prevalence and associated factors of occupational injuries among municipal solid waste collectors in four zones of Amhara region, Northwest Ethiopia. AB - BACKGROUND: Refuse collectors are at a high risk for fatal and non-fatal occupational accidents. This is more intensified in developing countries, like Ethiopia, due to physically demanding nature of the job. However, information on occupational injuries and related factors are almost non-existent in Ethiopia. Thus, the aim of this study was to assess the prevalence of occupational injuries and its associated factors. METHODS: A cross-sectional study was conducted among municipal solid waste collectors in four zones of Amhara region from February to May 2015. Computer generated simple random sampling technique was used to select the samples. Interviewer administrated questionnaires were used for the data collection process. Binary logistic regression was used to assess the association between outcome variables and explanatory variables. RESULTS: In this study, the annual prevalence of at least one occupational injury among solid waste workers was 34.3 % (95 % CI: 29.52, 39.10). Of these, 50.7 % of them were visited health facility to receive health care. The independent predictors of at least one occupational injury were shorter service years, low monthly salary, history of job related stress, and sleeping disturbance related to the job. Being illiterate, having lower monthly income, and those who reported sleeping disturbance were significantly and positively associated with severe occupational injuries of solid waste collectors. CONCLUSION: The magnitude of occupational injuries among municipal solid waste collectors is lower than other similar studies conducted in Ethiopia. Based on the finding of this and other studies, job rotation among work components, improvement of employees' income, job specific guideline regarding maximum production limits, and replacement of bags and bins with wheeled containers are an interventions expected to cope with the problem. There is also a need of specific periodic health surveillance (PHS) for refuse collectors to detect early signs of work related complaints and to monitor work ability. PMID- 27554262 TI - The probability of having advanced medical interventions is associated with age in out-of-hospital life-threatening situations. AB - BACKGROUND: The use of out-of-hospital emergency medical services by old and very old individuals is increasing. These patients frequently require complex evaluation and decision-making processes to determine a strategy of care, therapeutic choices or withdrawal of care in life-threatening situations. During out-of-hospital missions, thorough decision-making is difficult because of the limited amount of time and lack of direct access to medical charts or to pre existing advance directives. In this setting, age may be used as a proxy to determine strategy of care, therapeutic choices or withdrawal of care, particularly in relation to advanced medical interventions. We aimed to determine how an emergency physician's initiation of out-of-hospital advanced medical interventions varies with the patient's age. METHODS: We performed a retrospective analysis of the missions conducted by the emergency physicians staffed emergency medical services in a Swiss region. We used logistic regression analysis to determine whether the probability of receiving an advanced medical intervention was associated with the patient's age. RESULTS: Among 21,922 out-of hospital emergency adult missions requiring an emergency physician, the probability of receiving an advanced medical intervention decreased with age. It was highest among those aged 18 - 58 years and significantly lower among those aged >= 89 years (OR = 0.66; 95 % CI: 0.53 - 0.82). The probability of cardiopulmonary resuscitation attempts progressively decreased with age and was significantly lower for the three oldest age deciles (80 - 83, 84 - 88 and >= 89 years). CONCLUSION: The number of out-of-hospital advanced medical interventions significantly decreased for patients aged >= 89 years. It is unknown whether this lower rate of interventions was related only to age or to other medical characteristics of these patients, such as the number or severity of comorbidities. Thus, further studies are needed to confirm whether this observation corresponds to underuse of advanced medical interventions in very old patients. PMID- 27554263 TI - A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time dependent mechanical behavior of single cells. AB - Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease. PMID- 27554261 TI - Impact of food processing and detoxification treatments on mycotoxin contamination. AB - Mycotoxins are fungal metabolites commonly occurring in food, which pose a health risk to the consumer. Maximum levels for major mycotoxins allowed in food have been established worldwide. Good agricultural practices, plant disease management, and adequate storage conditions limit mycotoxin levels in the food chain yet do not eliminate mycotoxins completely. Food processing can further reduce mycotoxin levels by physical removal and decontamination by chemical or enzymatic transformation of mycotoxins into less toxic products. Physical removal of mycotoxins is very efficient: manual sorting of grains, nuts, and fruits by farmers as well as automatic sorting by the industry significantly lowers the mean mycotoxin content. Further processing such as milling, steeping, and extrusion can also reduce mycotoxin content. Mycotoxins can be detoxified chemically by reacting with food components and technical aids; these reactions are facilitated by high temperature and alkaline or acidic conditions. Detoxification of mycotoxins can also be achieved enzymatically. Some enzymes able to transform mycotoxins naturally occur in food commodities or are produced during fermentation but more efficient detoxification can be achieved by deliberate introduction of purified enzymes. We recommend integrating evaluation of processing technologies for their impact on mycotoxins into risk management. Processing steps proven to mitigate mycotoxin contamination should be used whenever necessary. Development of detoxification technologies for high-risk commodities should be a priority for research. While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments. PMID- 27554264 TI - Effects of non-vitamin K antagonist oral anticoagulants on fibrin clot and whole blood clot formation, integrity and thrombolysis in patients with atrial fibrillation. AB - Non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin and heparins in several clinical situations. With varying modes of action, the effects of NOACs on thrombus formation, integrity, and lysis is unknown. To determine whether two techniques of thrombelastography (TEG) and a micro-plate assay (MPA) provide novel data on thrombus formation, integrity and lysis in those taking a NOACs compared to warfarin and a control group taking aspirin. We assessed thrombogenesis, clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients-50 on aspirin, 50 on warfarin, and 82 on a NOAC (17 apixaban, 19 dabigatran and 46 rivaroxaban). Eleven of 16 TEG indices and 4 of 5 MPA indices differed (p <= 0.01) between those on aspirin, warfarin or a NOAC. Three TEG indices and 4 MPA indices differed (p < 0.01) between the NOACs. Time to initiation of clot formation was most rapid on apixaban, then rivaroxaban and slowest on dabigatran. The rate of clot formation was most rapid on dabigatran, then apixaban, and slowest on rivaroxaban. Clot density was greatest on rivaroxaban, then apixaban, but weakest on dabigatran. The rate of clot dissolution was most rapid in apixaban, then dabigatran, and slowest on rivaroxaban. The TEG and MPA identify major differences in thrombogenesis and fibrinolysis in different NOACs. These techniques may have value in investigating the effects of these drugs on haemostasis in a clinical setting, and in identifying those in need of targeted therapy. PMID- 27554265 TI - Effects of fetal calf serum on cGMP pathway and oocyte lipid metabolism in vitro. AB - Intracellular levels of cyclic nucleotides, such as cGMP, are involved in the regulation of adipocyte lipolysis. Cumulus-oocyte complexes (COCs) express enzymes that both synthesise (guanylate cyclase) and degrade (phosphodiesterase (PDE) 5A) cGMP. Because serum interferes with lipid metabolism, its effects on the cGMP pathway and lipid content in bovine COCs were examined. COCs were matured in medium containing fetal calf serum (FCS; 2% or 10%) or 0.4% bovine serum albumin (BSA; control). At both 2% and 10%, FCS decreased cGMP levels in COCs compared with BSA (0.64 and 1.04 vs 9.46 fmol per COC respectively; P<0.05) and decreased transcript levels of guanylate cyclase 1, soluble, beta 3 (GUCY1B3), whereas PDE5A levels were increased. FCS also affected the expression of genes related to lipolysis, increasing relative expression of perilipin 2 (PLIN2) and carnitine palmitoyltransferase 1B (CPT1B) in cumulus cells. Effects of FCS and cGMP on the lipid content of oocytes and embryos were evaluated by Nile red staining. COCs were matured with 10% FCS, FCS+10-5 M sildenafil (SDF), a PDE5 inhibitor, or 0.4% BSA. The lipid content was increased in oocytes matured in FCS compared with BSA (fluorescence intensity 20.1 vs 17.61 respectively; P<0.05), whereas the lipid content in oocytes matured in FCS+SDF (fluorescence intensity 16.33) was similar to that in the BSA-treated group (P>0.05). In addition, lipid content was higher in embryos from oocytes matured with FCS than BSA (fluorescence intensity 31.12 vs 22.31 respectively; P<0.05), but was increased even further in the FCS+SDF-treated group (fluorescence intensity 40.35; P<0.05), possibly due to a compensatory mechanism during embryo culture without SDF for the reduction in lipid content during IVM. The present study provides, for the first time, evidence that the cGMP pathway may be involved in lipid metabolism in bovine COCs and that this pathway is affected by FCS. PMID- 27554267 TI - From Cyclic CF3-ketimines to a Family of Trifluoromethylated Nazlinine and Trypargine Analogues. AB - An efficient (one- and two-step) synthesis of trifluoromethylated derivatives of the natural alkaloids nazlinine, trypargine, and homotrypargine was elaborated. Trifluoromethyl-substituted 5-7-membered cyclic imines were used as a masked carbonyl component in the Pictet-Spengler reaction with various tryptamines. As a result, this approach opens access to a family of alkaloid-like compounds bearing a CF3 group at position 1 of tetrahydro-beta-carboline. PMID- 27554266 TI - Palliative chemotherapy among people living in poverty with metastasised colon cancer: facilitation by primary care and health insurance. AB - BACKGROUND: Many Americans with metastasised colon cancer do not receive indicated palliative chemotherapy. We examined the effects of health insurance and physician supplies on such chemotherapy in California. METHODS: We analysed registry data for 1199 people with metastasised colon cancer diagnosed between 1996 and 2000 and followed for 1 year. We obtained data on health insurance, census tract-based socioeconomic status and county-level physician supplies. Poor neighbourhoods were oversampled and the criterion was receipt of chemotherapy. Effects were described with rate ratios (RR) and tested with logistic regression models. RESULTS: Palliative chemotherapy was received by less than half of the participants (45%). Facilitating effects of primary care (RR=1.23) and health insurance (RR=1.14) as well as an impeding effect of specialised care (RR=0.86) were observed. Primary care physician (PCP) supply took precedence. Adjusting for poverty, PCP supply was the only significant and strong predictor of chemotherapy (OR=1.62, 95% CI 1.02 to 2.56). The threshold for this primary care advantage was realised in communities with 8.5 or more PCPs per 10 000 inhabitants. Only 10% of participants lived in such well-supplied communities. CONCLUSIONS: This study's observations of facilitating effects of primary care and health insurance on palliative chemotherapy for metastasised colon cancer clearly suggested a way to maximise Affordable Care Act (ACA) protections. Strengthening America's system of primary care will probably be the best way to ensure that the ACA's full benefits are realised. Such would go a long way towards facilitating access to palliative care. PMID- 27554268 TI - Do Bone Graft and Cracking of the Sclerotic Cavity Improve Fixation of Titanium and Hydroxyapatite-coated Revision Implants in an Animal Model? AB - BACKGROUND: We previously introduced a manual surgical technique that makes small perforations (cracks) through the sclerotic bone shell that typically forms during the process of aseptic loosening ("crack" revision technique). Perforating just the shell (without violating the proximal cortex) can maintain overall bone continuity while allowing marrow and vascular elements to access the implant surface. Because many revisions require bone graft to fill defects, we wanted to determine if bone graft could further increase implant fixation beyond what we have experimentally shown with the crack technique alone. Also, because both titanium (Ti6Al4V) and hydroxyapatite (HA) implant surfaces are used in revisions, we also wanted to determine their relative effectiveness in this model. QUESTIONS/PURPOSES: We hypothesized that both (1) allografted plasma sprayed Ti6Al4V; and (2) allografted plasma-sprayed HA-coated implants inserted with a crack revision technique have better fixation compared with a noncrack revision technique in each case. METHODS: Under approval from our Institutional Animal Care and Use Committee, a female canine animal model was used to evaluate the uncemented revision technique (crack, noncrack) using paired contralateral implants while implant surface (Ti6Al4V, HA) was qualitatively compared between the two (unpaired) series. All groups received bone allograft tightly packed around the implant. This revision model includes a cylindrical implant pistoning 500 MUm in a 0.75-mm gap, with polyethylene particles, for 8 weeks. This engenders a bone and tissue response representative of the metaphyseal cancellous region of an aseptically loosened component. At 8 weeks, the original implants were revised and followed for an additional 4 weeks. Mechanical fixation was assessed by load, stiffness, and energy to failure when loaded in axial pushout. Histomorphometry was used to determine the amount and location of bone and fibrous tissue in the grafted gap. RESULTS: The grafted crack revision improved mechanical shear strength, stiffness, and energy to failure (for Ti6Al4V 27- to 69-fold increase and HA twofold increases). The histomorphometric analysis demonstrated primarily fibrous membrane ongrowth and in the gap for the allografted Ti6Al4V noncrack revisions. For allografted HA noncrack revisions, bone ongrowth at the implant surface was observed, but fibrous tissue also was present in the inner gap. Although both Ti6Al4V and HA surfaces showed improved fixation with grafted crack revision, and Ti6Al4V achieved the highest percent gain, HA demonstrated the strongest overall fixation. CONCLUSIONS: The results of this study suggest that novel osteoconductive or osteoinductive coatings and bone graft substitutes or tissue-engineered constructs may further improve bone implant fixation with the crack revision technique but require evaluation in a rigorous model such as presented here. CLINICAL RELEVANCE: This experimental study provides data on which to base clinical trials aimed to improve fixation of revision implants. Given the multifactorial nature of complex human revisions, such a protocoled clinical study is required to determine the clinical applicability of this approach. PMID- 27554269 TI - Sometimes, It's Just Black and White: Dark Urine and Pallor in a 2-Year-Old Boy. PMID- 27554270 TI - Assessing Initial Validity and Reliability of a Beverage Intake Questionnaire in Hispanic Preschool-Aged Children. AB - BACKGROUND: Understanding the relationship between high-calorie beverage consumption and weight gain requires an accurate report of dietary intake. A critical need exists to develop and test the psychometrics of brief quantitative tools for minority pediatric populations. OBJECTIVE: To modify the adult beverage intake questionnaire (BEVQ-15) for Hispanic preschool-aged children (BEVQ-PS) and test its validity and test-retest reliability in children aged 3 to 5 years. DESIGN: Cross-sectional. The modified quantitative 12-beverage category questionnaire assessed consumption of water, fruit juice, sweetened juice drinks, whole milk, reduced-fat milk, low-fat milk, flavored milk, carbonated sweetened drinks, diet carbonated drinks, sweet tea, tea with or without artificial sweetener, and sport drinks consumed during the past month. Hispanic mothers (n=109) recruited from day-care centers provided one 4-day food intake record (FIR) and completed two BEVQ-PS surveys during a 2-week period for their preschool-aged child. Data collection was conducted through one-on-one interviews in Spanish. Validity was assessed by comparing amounts (in grams) and energy intake (in kilocalories) for each beverage category between the first BEVQ-PS and the mean of the FIRs using paired t tests and Pearson's correlation coefficient. Criteria for validity were nonsignificant mean differences in grams and kilocalories from the first BEVQ-PS and mean of the FIRs beverage categories, and significant correlation coefficients between beverage categories. Test-retest reliability was assessed by comparing grams and kilocalories for each beverage category in the first BEVQ-PS with those from the second BEVQ-PS using Pearson's correlation coefficient. The criterion for reliability was a significant correlation coefficient between beverage categories. Significance was set at P<0.05. RESULTS: Mean differences between the first BEVQ-PS and FIR for water (42.4+/-23.1 g), sweetened juice drinks (-1.6+/-11.0 g), whole milk (18.3+/-9.91 g), sweetened carbonated drinks (-13.0+/-7.9 g), and total sugar-sweetened beverages (SSB) (1.4+/-8.9 g) were not significantly different, but were significantly correlated (r=0.20 to 0.37; P<0.05). Thus, validity criteria were met. With the exception of flavored milk and tea with or without artificial sweeteners, the remaining beverage categories-total beverages and SSB-in the first BEVQ-PS were correlated with those from the second BEVQ-PS (r=0.20 to 0.68; P<0.05), meeting reliability criteria. CONCLUSIONS: Researchers and clinicians may use the BEVQ-PS to assess SSB, water, and whole-milk intake in Hispanic children. Additional modifications should be evaluated to assess total beverage intake. PMID- 27554271 TI - The journey toward safer and optimized blood service in China: national strategy and progress. AB - BACKGROUND: The objective was to analyze and evaluate the effects of strategic measures the Chinese government attempted and undertook throughout the fast changing and difficult transition periods of the blood service system. STUDY DESIGN AND METHODS: We systematically reviewed data and information regarding policy, blood collection, service system, and clinical transfusion practice, which were the most representative indicators on a national level from 1978 to 2015. RESULTS: Blood donation in China has successfully transitioned from paid donation, then compulsory (but nonremunerated) donation, to voluntary nonremunerated donation. The volume of blood collection has steadily increased from 4,000,000 red blood cell (RBC; 200 mL/unit) units in 1998 to 22,000,000 RBC units in 2014. The percentage of human immunodeficiency virus (HIV) transfusion transmitted infections in newly diagnosed HIV/AIDS has reduced from 29.6% in 2005 to less than 0.15% in 2013. The use of component therapy has increased from 18% in 1989 to 99% in 2014. CONCLUSIONS: Involvement of the government through enforcement of new statutes and regulations helped improve blood safety and clinical transfusion practice. PMID- 27554272 TI - Characterization of virulence factors, antimicrobial resistance pattern and clonal complexes of group B streptococci isolated from neonates. AB - Between January and December 2013, swab samples were taken for the throat and external ear canals of 1037 newborns for screening of Group B Streptococcus (GBS or S. agalactiae). Isolates were analyzed form Multilocus sequence typing (MLST), capsular type, virulence genes and antibiotic susceptibility. The MLST analysis of 19 GBS isolates showed 8 sequence types (STs). Overall the most common STs were ST19 and ST28. Other STs were ST1, ST4, ST8, ST12, ST335 and ST734 (a new ST). The most common clonal complexes (CCs) were CC19 (68.4%) and CC10 (21%). The scpB, hlyB and bca virulence genes were detected in all STS, while the bac gene was predominant in ST12 with capsular type (CT) Ib. The IS1548 and the rib genes were particularly prevalent in CTIII and were detected in isolates belong to ST19, ST335 and ST734 and were grouped in CC19. All isolates were susceptible to penicillin, vancomycin, linezolid and quinupristin-dalfopristin. Resistance to tetracycline was observed in all 19 (100%) strains and was correlated with presence of the tetM gene except for one isolate with ST12. All the ST8 and ST12 isolates were resistant to macrolide carrying two resistance genes; the ermTR and the ermB, respectively. The results of this study showed that the CC19 was a major clone in the neonatal intensive care unit (NICU) of Imam Khomeini hospital which can cause severe infections in susceptible neonates (particularly in premature infants). As a result, an intensive infection control policy is needed to prevent the spread of this clone. PMID- 27554273 TI - Antibiofilm effect of antimicrobials used in the therapy of mycobacteriosis. AB - Rapidly growing mycobacteria (RGM) are opportunistic pathogens found in the environment. When in biofilms, mycobacteria is highly resistant to antibacterial treatments. The purpose of this study is to evaluate the antibiofilm activity of antimicrobials commonly used in therapy against mycobacteria. The antimicrobial susceptibility of Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium massiliense was determined in planktonic and sessile populations. The antimicrobials amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole were tested. For each drug, it was evaluated the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Results showed although, the antimicrobials tested are used as an alternative therapy for RGM, M. abscessus proved to be resistant to clarithromycin, beside that, M. massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Moreover, the inhibition of biofilm formation and its destruction have not been fully met. Considering that the biofilms are a known form of bacterial resistance, the failure of alternatives to inhibit or destroy biofilms can trigger the recurrence of infections. In RGM, besides causing treatment failures, biofilms are a factor of pathogenic risk, since these microorganisms are found in environmental sources and can cause infections easily. PMID- 27554274 TI - A local innate immune response against Trypanosoma cruzi in the human placenta: The epithelial turnover of the trophoblast. AB - Congenital Chagas disease, caused by Trypanosoma cruzi, is partially responsible for the progressive globalization of Chagas disease despite of its low transmission rate. The probability of congenital transmission depends on complex interactions between the parasite, the maternal and fetus/newborn immune responses and placental factors, being the latter the least studied one. During transplacental transmission, the parasite must cross the placental barrier where the trophoblast, a continuous renewing epithelium, is the first tissue to have contact with the parasite. Importantly, the epithelial turnover is considered part of the innate immune system since pathogens, prior to cell invasion, must attach to the surface of cells. The trophoblast turnover involves cellular processes such as proliferation, differentiation and apoptotic cell death, all of them are induced by the parasite. In the present review, we analyze the current evidence about the trophoblast epithelial turnover as a local placental innate immune response. PMID- 27554275 TI - Host environmental signals and effects on biofilm formation. AB - Biofilm matrix formation is a phenotype linked to the ability to survive a hostile host environment that includes the presence of antimicrobial peptides and serum factors. Multiple hormones and other host derived factors have been shown to function as exogenous quorum signaling compound homologs that inform microbes of their in situ presence, thus triggering a shift from a planktonic to the sessile biofilm phenotype. The focus of this review is to describe the impact various host-derived factors have on the initial steps required for biofilm formation, i.e., adherence to host surfaces and multiplication in the host. PMID- 27554276 TI - Neutralization of MMP-2 protects Staphylococcus aureus infection induced septic arthritis in mice and regulates the levels of cytokines. AB - Matrix metalloproteinases (MMPs) are crucial players in Staphylococcus aureus mediated synovial tissue destruction in the pathogenesis of septic arthritis. Bacterial insult increases proteolytic matrix fragments by activated chondrocytes and synovial fibroblasts leading to induction of matrix metalloproteinases. Tissue destruction via MMPs induced by bacterial products, necrotic tissues and proinflammatory cytokines have been reported. Cytokines like TNF-alpha, IL-1beta released from host cells in response to S. aureus infection promote cartilage degradation by stimulating the production of MMPs. Antibiotic treatment can eradicate invading bacteria but elevated levels of cytokines and cytokines induced MMPs activation lead to progressive and devastating bone and cartilage destruction even after bacterial clearance. Like other MMPs, MMP-2 also contributes to extracellular matrix degradation in different types of arthritis. Release of certain pro inflammatory cytokines can also be regulated by MMP-2 activation leading to further tissue destruction. The role of MMP-2 in the pathogenesis of S. aureus infection induced septic arthritis and its influence on cytokines regulation needs further investigation. Whether neutralization of MMP-2 provides protection against Staphylococcus aureus infection induced septic arthritis in mice is an obvious question. Here we reported that neutralization of MMP-2 during S. aureus infection induced septic arthritis might be beneficial for preventing infection induced extracellular matrix destruction thereby decreasing bacterial burden in synovial tissues and regulating inflammatory cytokines in arthritic mice. PMID- 27554277 TI - Ultrasonic-assisted green synthesis of flower like silver nanocolloids using marine sponge extract and its effect on oral biofilm bacteria and oral cancer cell lines. AB - The knowhow followed for synthesis, characterization and application of nanomaterials has become an important branch of nanoscience. The use of marine sponges for the synthesis of metal nanoparticles is still in the budding level of current nanobiotechnology. This paper reports a single step one pot biosynthesis utilizing marine sponge (Haliclona exigua) extract as a reducing agent by means of a conventional ultrasonic bath on the formation and growth of flower like silver nanocolloids. These silver nanocolloids were characterized through UV visible spectroscopy, High Resolution Transmission Electron Microscope, Fourier Transform Infrared spectroscopy and X-ray Diffractometer. Further, antibacterial activity and antiproliferative activity were done against oral biofilm bacteria and oral cancer cell lines for the biosynthesized flower like silver nanocolloids. Water soluble organic amines were responsible for the syntheses of nanomaterials which have a size range from 100 to 120 nm. An average size of 9.1 mm zone of inhibition was recorded with 10.0 MUg of silver nanocolloids against oral biofilm bacteria. The estimated half maximal inhibitory concentration value for flower like silver nanocolloids was 0.6 MUg/ml for oral cancer cell lines. PMID- 27554278 TI - Myrcia ovata Cambessedes essential oils: A proposal for a novel natural antimicrobial against foodborne bacteria. AB - This paper reports the innovative antibacterial activity of essential oils (EOs) from nine Myrcia ovata Cambessedes plants against eight foodborne bacteria. Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Enterococcus faecalis and Pseudomonas aeruginosa were the most susceptible bacteria to EOs. In particular, the P. aeruginosa, which is usually resistant to antimicrobials agents, was extremely sensitive to some EOs. The gram-positive and gram-negative bacteria were inhibited and eliminated with minimum EOs concentrations ranging from 0.78 to 25 MUL/mL. The Serratia marcensces and Escherichia coli were less susceptible to EOs alone. Consequently, some EOs combinations were investigated by checkerboard method against these bacteria and a synergistic effect was obtained. Myrcia ovata Cambessedes EOs showed high inhibitory and bactericidal effects against foodborne bacteria might be an interesting alternative for future applications as natural antimicrobials in food systems. PMID- 27554279 TI - Rotavirus activates dendritic cells derived from umbilical cord blood monocytes. AB - Rotavirus is the most common cause of acute infectious diarrhea in human neonates and infants. However, the studies aimed at dissecting the anti-virus immune response have been mainly performed in adults. Dendritic cells (DCs) play a crucial role in innate and acquired immune responses. Therefore, it is very important to determine the response of neonatal and infant DCs to rotavirus and to compare it to the response of adult DCs. Thus, we determined the response of monocyte-derived DCs from umbilical cord blood (UCB) and adult peripheral blood (PB) to rotavirus in vitro. It was found that the rotavirus and its genome, composed of segmented doubled stranded RNA (dsRNA), induced the activation of neonatal DCs, as these cells up-regulated the levels of CD40, CD86, MHC II, TLR-3 and TLR-4, the production of cytokines IL-6, IL-12/23p40, IL-10, TGF-beta (but not of IL-12p70), and the message for TNF-alpha and IFN-beta. This activation enabled the neonatal DCs to induce a strong proliferation of allogeneic CD4+ T cells and the production of IFN-gamma. Moreover, neonatal DCs could be infected by rotavirus and sustain its replication. Neonatal DCs had a similar response as adult DCs towards rotavirus and its genome. However, adult DCs had a biased pro inflammatory response compared to neonatal DCs, which showed a biased regulatory profile, as they produced higher levels of IL-10 and TGF-beta, and were less efficient in inducing a Th1 type response. So it can be concluded that rotavirus and its genome can induce the activation of neonatal DCs in spite of their tolerogenic bias. PMID- 27554280 TI - Return to sport following clavicle fractures: a systematic review. AB - INTRODUCTION: This review aims to provide information on the return rates and return times to sport following clavicle fractures. SOURCES OF DATA: A systematic search of Medline, EMBASE, CINAHAL, Cochrane, Web of Science, PEDro, SPORTDiscus, Scopus and Google Scholar was performed using the keywords 'clavicle', 'clavicular', 'fractures', 'athletes', 'sports', 'non-operative', 'conservative', 'operative', 'return to sport'. AREAS OF AGREEMENT: Twenty-three studies were included: 10 reported on mid-shaft fractures, 14 on lateral fractures. The management principles for athletic patients were to attempt non-operative management for undisplaced fractures to undertake operative intervention for displaced lateral fractures and to recommend operative intervention for displaced mid-shaft fractures. AREAS OF CONTROVERSY: The optimal surgical modality for mid shaft and lateral clavicle fractures. GROWING POINTS: Operative management of displaced mid-shaft fractures offers improved return rates and times to sport compared to non-operative management. Suture fixation and non-acromio-clavicular joint (ACJ)-spanning plate fixation of displaced lateral fractures show promising results. AREAS TIMELY FOR DEVELOPING RESEARCH: Future prospective studies should aim to establish the optimal treatment modalities for clavicle fractures. PMID- 27554281 TI - Wrist arthroscopy in the management of articular distal radius fractures. AB - INTRODUCTION: Fractures of the distal radius account for 15% of all fractures. The use of arthroscopy is increasingly popular in the last years, with the goal to achieve a better anatomical reduction of the articular fragments. SOURCES OF DATA: We searched the literature on Medline (PubMed), Web of Science and Scopus databases using the combined keywords 'wrist', 'distal radial fracture', 'distal radius fracture' and 'arthroscopy'. Twenty-eight studies were identified. The quality of the studies was assessed using the Coleman Methodological Score. AREAS OF AGREEMENT: Arthroscopy allows to detect intra-articular, ligamentous and triangular fibrocartilage complex injuries in an acute setting with a better prognosis. Arthroscopy increases the quality of the intra-articular reduction compared to fluoroscopy. AREAS OF CONTROVERSY: The main limitation of the selected studies is the short follow-up: the average follow-up in 20 studies was 12 months, a period long enough to assess functional outcomes, but not to assess the occurrence of post-traumatic degenerative changes and their impact on function. Better stratification of the fracture population is needed. GROWING POINTS: The shorter recovery time and the low incidence of adverse effects are the main advantages of this new technology. AREAS TIMELY FOR DEVELOPING RESEARCH: There is need to perform randomized controlled trials reporting on the use of volar locking plates as, at the present time, they are the standard management for these fractures. In addition, the different pattern of fracture should be better classified to manage the patients who will benefit after the management. PMID- 27554282 TI - The changing face of the English National Health Service: new providers, markets and morality. AB - INTRODUCTION: One significant change in the English National Health Service (NHS) has been the introduction of market mechanisms. This review will explore the following questions: should we have markets in healthcare? What is the underlying philosophy of introducing more market mechanisms into the NHS? What are the effects of this and does it change the NHS beyond anything Bevan might have imagined in 1948? SOURCES OF DATA: The review will use empirical studies, philosophical literature, bioethics discussion, policy and NHS documents. AREAS OF AGREEMENT: The NHS is facing unprecedented challenges at the beginning of the 21st century, with funding levels not meeting the increase in demand. AREAS OF CONTROVERSY: The extent and appropriate role for market mechanisms in the NHS is hotly debated. It will be argued that we are moving towards a more market-based NHS and the possible effects of this will be discussed. GROWING POINTS: Rarely are the policy changes in the NHS evidence based in any meaningful way and they are often driven by ideological considerations rather than clear evidence. There needs to be a greater reliance on evidence of what works and a continuing commitment to healthcare as a societal good. AREAS TIMELY FOR DEVELOPING RESEARCH: There needs to be a discussion of what the NHS should be-a funder and provider, a funder or a partial funder? How the balance of power between regulators, different types of provider, commissioners and ultimately patients will play out in this changing environment are also areas for future study. PMID- 27554283 TI - Outcomes of patients with non-melanoma solid tumours receiving self-funded pembrolizumab at Chris O'Brien Lifehouse. AB - BACKGROUND: Immunotherapy agents show anti-cancer activity in several solid cancers. Efficacy in non-melanoma solid tumours for non-approved indications is unknown. AIM: To evaluate patient and disease characteristics, rate and duration of response, and toxicity of self-funded pembrolizumab in patients with non melanoma solid cancers. METHOD: Retrospective review describing outcomes and toxicity of self-funded pembrolizumab in patients with non-melanoma solid cancers treated at Chris O'Brien Lifehouse. RESULTS: From April 2015 to December 2015, 21 patients received or were planned to receive self-funded pembrolizumab. The median age was 50 years (16-76), 28 and 10% had an Eastern Cooperative Oncology Group performance status of 2, and 3-4 respectively. Sixty-two percent received at least two to four lines of prior drug treatment. Median follow-up was 3.0 months (range, 0.4-9.6). Fourteen (67%) patients requested pembrolizumab. Pembrolizumab was clinician offered for 7 (33%) patients. Patients who requested pembrolizumab had worse outcomes. Three patients died before receiving pembrolizumab. Of the 18 patients that received at least one dose, a partial response was observed in 3 (17%). Progressive disease occurred in 83%. Four patients received only one cycle of pembrolizumab and died after a median of 27 days (range 13-43). Immune-related adverse events of any grade occurred in 33%. No grade 3-4 events were observed. CONCLUSION: Pembrolizumab was well tolerated. Meaningful responses were observed in 17% of treated patients. Response continues after 5-6.5 months follow-up in 11% and >8 months of follow-up for the other responding patient. Financial impact to the patient can be substantial. Outcomes for 33% were poor with three patients dying prior to receiving therapy and four dying within weeks of receiving one dose. This highlights issues regarding the careful selection of patients, futility of anti-cancer therapy at the end-of-life and patients' perceived benefit of receiving this therapy. PMID- 27554284 TI - Vitamin insufficiencies/deficiencies in relation to sickle cell disease severity and associated morbidity. PMID- 27554285 TI - Role of vacancies, light elements and rare-earth metals doping in CeO2. AB - The magnetic properties and electronic structures of pure, doped and defective cerium oxide (CeO2) have been studied theoretically by means of ab initio calculations based on the density function theory (DFT) with the hybrid HF/DFT technique named PBE0. Carbon (C), nitrogen (N), phosphorus (P), sulphur (S), lanthanum (La) and praseodymium (Pr) doped in CeO2 and CeO2 containing oxygen vacancies (Ov) were considered. Our spin-polarized calculations show that C, N, Pr dopants and Ov defects magnetize the non-magnetic CeO2 in different degree. The optical band gap related to photocatalysis for pure CeO2, corresponding to the ultraviolet region, is reduced obviously by C, N, S, Pr impurities and oxygen vacancies, shifting to the visible region and even further to the infrared range. Especially, N-, S- and Pr-doped CeO2 could be used to photocatalytic water splitting for hydrogen production. As the concentration of Ov increasing up to 5%, the CeO2 exhibits a half-metallic properties. PMID- 27554286 TI - ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling. AB - The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of neurodegenerative disorders. The Keap1-binding partner and autophagy receptor SQSTM1/p62 has also recently been linked genetically to ALS-FTLD, with some missense mutations identified in patients mapping within or close to its Keap1-interacting region (KIR, residues 347-352). Here we report the effects on protein function of four different disease associated mutations of SQSTM1/p62 which affect the KIR region. Only mutations mapping precisely to the KIR (P348L and G351A) were associated with a loss of Keap1 binding in co immunoprecipitations comparable to wild-type SQSTM1/p62. These selective effects on Keap1 recognition were entirely rational based on protein structural models. Consistent with impaired Keap1 binding, the P348L and G351A KIR mutants showed reduced ability to activate Nrf2 signalling compared to wild-type SQSTM1/p62 in antioxidant response element (ARE)-luciferase reporter assays. The results suggest that SQSTM1 mutations within the KIR of SQSTM1/p62 contribute to aetiology of some cases of ALS-FTLD through a mechanism involving aberrant expression or regulation of oxidative response genes. PMID- 27554287 TI - The effects of the concentration-dependent erythrocyte distribution of TAK-802, a potent acetylcholinesterase inhibitor, on rat pharmacokinetics. AB - The purpose of this study was to investigate the effect of the concentration dependent erythrocyte distribution of TAK-802, a potent acetylcholinesterase inhibitor, on rat pharmacokinetics. In an ascending oral dose study, the maximum plasma concentration (Cmax ) of TAK-802 increased in a dose-dependent manner. The time to reach Cmax decreased as the dose increased, whereas the total clearance was independent of the tested dose range. In this intravenous (i.v.) ascending dose study in rats, the apparent distribution volumes at steady state decreased, and the apparent terminal elimination rate constants increased with TAK-802 dose escalation. A marked concentration dependency was observed in an associated in vitro erythrocyte distribution study. The in vitro erythrocyte distribution study results and a relationship analysis between the plasma and blood concentrations of TAK-802 after i.v. dosing revealed that the characteristics of the erythrocyte distribution could be expressed by Langmuir's adsorption formula. The concentration-time profiles of TAK-802 in plasma and whole blood calculated using a nonlinear pharmacokinetic model incorporating the concentration-dependent erythrocyte distribution with optimized parameters fit well to the observed plasma and blood concentration profiles obtained from the i.v. ascending dose study. These results indicate that the concentration-dependent erythrocyte distribution plays a major role in the nonlinear pharmacokinetics of TAK-802 in rats. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27554289 TI - Spatially modulated spin structure (SMSS) in BiFeO3-30 years later. PMID- 27554290 TI - Electro-optical Memory of a Nanoengineered Amorphous Blue-Phase-III Polymer Scaffold. AB - An electro-optical (EO) memory device is presented, which is based on a 3D nanostructured polymer scaffold of the amorphous blue phase III (BPIII) of cholesteric liquid crystals (LCs), which can impart optical isotropy, optical activity, and sub-millisecond EO response of BPIII to conventional nematic LCs. This functional scaffold also enables the first experimental observation of the long debated structure of BPIII. PMID- 27554288 TI - The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis. AB - Epithelia function as barriers against environmental insults and express the transcription factor aryl hydrocarbon receptor (AhR). However, AhR function in these tissues is unknown. Here we show that AhR regulates multiciliogenesis in both murine airway epithelia and in Xenopus laevis epidermis. In air-exposed airway epithelia, induction of factors required for multiciliogenesis, including cyclin O (Ccno) and Multicilin (Mcidas), is AhR dependent, and air exposure induces AhR binding to the Ccno promoter. Submersion and hypoxic conditions impede AhR-dependent Ccno induction. This is mediated by the persistence of Notch signalling, as Notch blockade renders multiciliogenesis and Ccno induction by AhR independent from air exposure. In contrast to Ccno induction, air exposure does not induce the canonical AhR target cytochrome P450 1a1 (Cyp1a1). Inversely, exposure to AhR ligands induces Cyp1a1 but not Ccno and impeded ciliogenesis. These data indicate that AhR involvement in detoxification of environmental pollutants may impede its physiological role, resulting in respiratory pathology. PMID- 27554291 TI - [Contextual indicators to assess social determinants of health and the Spanish economic recession]. AB - OBJECTIVE: To provide indicators to assess the impact on health, its social determinants and health inequalities from a social context and the recent economic recession in Spain and its autonomous regions. METHODS: Based on the Spanish conceptual framework for determinants of social inequalities in health, we identified indicators sequentially from key documents, Web of Science, and organisations with official statistics. The information collected resulted in a large directory of indicators which was reviewed by an expert panel. We then selected a set of these indicators according to geographical (availability of data according to autonomous regions) and temporal (from at least 2006 to 2012) criteria. RESULTS: We identified 203 contextual indicators related to social determinants of health and selected 96 (47%) based on the above criteria; 16% of the identified indicators did not satisfy the geographical criteria and 35% did not satisfy the temporal criteria. At least 80% of the indicators related to dependence and healthcare services were excluded. The final selection of indicators covered all areas for social determinants of health, and 62% of these were not available on the Internet. Around 40% of the indicators were extracted from sources related to the Spanish Statistics Institute. CONCLUSIONS: We have provided an extensive directory of contextual indicators on social determinants of health and a database to facilitate assessment of the impact of the economic recession on health and health inequalities in Spain and its autonomous regions. PMID- 27554292 TI - Organocatalyzed Atom Transfer Radical Polymerization Using N-Aryl Phenoxazines as Photoredox Catalysts. AB - N-Aryl phenoxazines have been synthesized and introduced as strongly reducing metal-free photoredox catalysts in organocatalyzed atom transfer radical polymerization for the synthesis of well-defined polymers. Experiments confirmed quantum chemical predictions that, like their dihydrophenazine analogs, the photoexcited states of phenoxazine photoredox catalysts are strongly reducing and achieve superior performance when they possess charge transfer character. We compare phenoxazines to previously reported dihydrophenazines and phenothiazines as photoredox catalysts to gain insight into the performance of these catalysts and establish principles for catalyst design. A key finding reveals that maintenance of a planar conformation of the phenoxazine catalyst during the catalytic cycle encourages the synthesis of well-defined macromolecules. Using these principles, we realized a core substituted phenoxazine as a visible light photoredox catalyst that performed superior to UV-absorbing phenoxazines as well as previously reported organic photocatalysts in organocatalyzed atom transfer radical polymerization. Using this catalyst and irradiating with white LEDs resulted in the production of polymers with targeted molecular weights through achieving quantitative initiator efficiencies, which possess dispersities ranging from 1.13 to 1.31. PMID- 27554293 TI - Subunit vaccine H56/CAF01 induces a population of circulating CD4 T cells that traffic into the Mycobacterium tuberculosis-infected lung. AB - The capacity of CD4 T cells to protect against Mycobacterium tuberculosis (Mtb) is governed by their ability to localize to the lung site of infection. Subunit vaccine H56/CAF01, a liposome-adjuvanted fusion protein of Mtb antigens Ag85B, ESAT-6, and Rv2660, conferred durable protection and elicited polyfunctional CD4 T cells that preferentially localized to the lung parenchyma. These lung-resident T cells had reduced KLRG1 and increased CXCR3 expression, an intermediate state of Th1 differentiation that has been associated with Mtb protection. Importantly, KLGR1- CXCR3+ cells were also enriched in the lung vasculature and peripheral circulation of vaccinated animals, but not controls. Moreover, S1P1R blockade rapidly cleared this population from the blood and adoptive transfer of T cells recovered from the vasculature of vaccinated, but not control, mice efficiently trafficked into the Mtb-infected lung parenchyma. Thus, durable immunity elicited by H56/CAF01 vaccination is associated with the maintenance of circulating CD4 T cells that selectively home to the lung parenchyma. PMID- 27554294 TI - Intestinal tuft cells: epithelial sentinels linking luminal cues to the immune system. AB - Epithelial tuft cells (also known as "brush" cells in the airway) were first identified morphologically, almost six decades ago in the trachea and gastro intestinal tract, but their function remained mysterious until three almost simultaneous reports recently revealed their essential role in the initiation of immune type 2 responses. This is a new and exciting example of cooperation between the epithelial and haematopoietic compartments for the management of enteric parasite infections. Here we review tuft cell functions and markers, and anchors epithelial tuft cells within the current paradigm of type 2 immune responses. PMID- 27554296 TI - A double edged sword: Schistosoma mansoni Sm29 regulates both Th1 and Th2 responses in inflammatory mucosal diseases. PMID- 27554295 TI - Mechanisms of inflammation-driven bacterial dysbiosis in the gut. AB - The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut. PMID- 27554297 TI - Neutrophil pyroptosis mediates pathology of P. aeruginosa lung infection in the absence of the NADPH oxidase NOX2. AB - Nod-like receptor family, CARD domain-containing 4 (NLRC4) inflammasome activation is required for efficient clearance of intracellular pathogens through caspsase-1-dependent pyroptosis in macrophages. Although neutrophils have a critical role in protection from Pseudomonas aeruginosa infection, the mechanisms regulating inflammasome-mediated pyroptosis in neutrophils and its physiological role are largely unknown. We sought to determine the specific mechanisms regulating neutrophil pyroptosis in P. aeruginosa strain PAO1 (PAO1) lung infection and to identify the pathological role of this process. Nox2-/- models with reduced neutrophil antibacterial activity exhibited increased neutrophil pyroptosis, which was mediated by flagellin, a pathogenic PAO1 component. We also demonstrate that PAO1-induced pyroptosis depended on NLRC4 and Toll-like receptor 5 (TLR5) in neutrophils generated from Nlrc4-/- or Tlr5-/- mice. Our study reveals previously unknown mechanisms and physiological role of neutrophil pyroptosis during P. aeruginosa lung infection. Furthermore, our findings regarding neutrophil pyroptosis in the context of neutrophil dysfunction may explain the causes of acute and/or chronic infectious diseases discovered in immune-compromised patients. PMID- 27554298 TI - Echocardiography Combined With Cardiopulmonary Exercise Testing for the Prediction of Outcome in Idiopathic Pulmonary Arterial Hypertension. AB - BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension. The aim of the study was to evaluate the incremental prognostic value of echocardiography of the right ventricle and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred and thirty treatment-naive patients with idiopathic pulmonary arterial hypertension were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6 min walk distance plus an increase in functional class, or nonelective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic, and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 +/- 304 days, 54 patients experienced CW (53%). Among demographic, clinical, and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (model 1). With addition of echocardiographic and CPET variables (model 2), peak O2 pulse (peak Vo2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (area under the curve, 0.81 vs 0.66, respectively; P = .005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC + low O2 pulse showed a 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk, 41.1 and 25.3, respectively), compared with high RVFAC + high O2 pulse (P = .0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration. PMID- 27554299 TI - Pulmonary Hypertension in Diffuse Parenchymal Lung Diseases. AB - Pulmonary hypertension (PH) can be triggered by any number of disease processes that result in increased pulmonary vascular resistance. Although historically associated with idiopathic pulmonary arterial hypertension (PAH), most patients with PH do not have the idiopathic subtype, but rather PH associated with another underlying diagnosis, such as left heart or lung disease. The World Health Organization (WHO) classification of PH helps conceptualize the different categories based on presumed etiology. WHO group 3 is PH associated with lung disease. This review focuses on PH in diffuse parenchymal lung diseases (DPLDs), such as the idiopathic interstitial pneumonias and other more rare forms of DPLD. Although there are clear associations of PH with DPLD, the exact pathophysiologic mechanisms and full clinical significance remain uncertain. Treatment of PH related to DPLD remains investigational, but an area of great interest given the negative prognostic implications and the growing number of available pulmonary vasoactive agents. PMID- 27554300 TI - Long-Acting Bronchodilator Initiation in COPD and the Risk of Adverse Cardiopulmonary Events: A Population-Based Comparative Safety Study. AB - BACKGROUND: Long-acting bronchodilators, including long-acting beta2-agonists (LABA) and the anticholinergic tiotropium, are recommended as initial maintenance therapy in COPD. Studies to date have been limited in size and reported ambivalent results on the comparative risk of cardiovascular, cerebrovascular, and pulmonary adverse events between these two long-acting bronchodilators. Moreover, little information is available for the period when treatment is first initiated, a time when subjects may be especially at risk. METHODS: We identified a cohort of new users of long-acting bronchodilators between 2002 and 2012, age 55 or older, from the United Kingdom's Clinical Practice Research Datalink. Patients initiating tiotropium were matched on high-dimensional propensity scores and prior inhaled corticosteroid use with patients initiating LABAs, and followed for 1 year for the occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia. RESULTS: A total of 26,442 tiotropium initiators were matched to 26,442 LABA initiators, mainly single inhalers combined with inhaled corticosteroids. The hazard ratio of acute myocardial infarction associated with tiotropium initiation, relative to LABA initiation, was 1.10 (95% CI, 0.88-1.38), whereas for stroke it was 1.02 (95% CI, 0.78-1.34), for arrhythmia 0.81 (95% CI, 0.60-1.09), and heart failure 0.90 (95% CI, 0.79 1.02). The incidence of pneumonia was significantly less with tiotropium (hazard ratio, 0.81; 95% CI, 0.72-0.92). CONCLUSION: COPD treatment initiation with tiotropium compared with LABA does not increase cardiovascular risk in the first year of treatment. The risk of pneumonia is higher with LABA, a likely effect of the inhaled corticosteroids present in many LABA inhalers used in real world clinical practice. PMID- 27554301 TI - Effects of disinfectants against norovirus virus-like particles predict norovirus inactivation. AB - Human noroviruses (NoVs) are a major cause of epidemic and sporadic acute gastroenteritis worldwide. Public and personal hygiene is one of the most important countermeasures for preventing spread of NoV infection. However, no a practicable cell culture system for NoV had been developed, initial tests of the virucidal effectiveness of anti-NoV disinfectants and sanitizers have been performed using surrogate viruses. In this study, NoV virus-like particles (VLPs) were used as a new surrogate for NoVs and a method for evaluating NoV inactivation using them developed. This method is based on morphological changes in VLPs after treatment with sodium hypochlorite. VLP specimens were found to become deformed and degraded in a concentration-dependent manner. Based on these results, the effects of sodium hypochlorite on VLPs were classified into four phases according to morphological changes and number of particles. Using the criteria thus established, the efficacy of ethanol, carbonates and alkali solutions against VLPs was evaluated. Deformation and aggregation of VLPs were observed after treatment with these disinfectants under specific conditions. To determine the degradation mechanism(s), VLPs were examined by SDS-PAGE and immunoblotting after treatment with sodium hypochlorite and ethanol. The band corresponding to the major capsid protein, VP1, was not detected after treatment with sodium hypochlorite at concentrations greater than 500 ppm, but remained after treatment with ethanol. These results suggest that VLPs have excellent potential as a surrogate marker for NoVs and can be used in initial virucidal effectiveness tests to determine the mechanism(s) of chemical agents on NoVs. PMID- 27554302 TI - Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia. AB - Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia. PMID- 27554303 TI - On standardized relative survival. AB - Cancer survival comparisons between cohorts are often assessed by estimates of relative or net survival. These measure the difference in mortality between those diagnosed with the disease and the general population. For such comparisons methods are needed to standardize cohort structure (including age at diagnosis) and all-cause mortality rates in the general population. Standardized non parametric relative survival measures are evaluated by determining how well they (i) ensure the correct rank ordering, (ii) allow for differences in covariate distributions, and (iii) possess robustness and maximal estimation precision. Two relative survival families that subsume the Ederer-I, Ederer-II, and Pohar-Perme statistics are assessed. The aforementioned statistics do not meet our criteria, and are not invariant under a change of covariate distribution. Existing methods for standardization of these statistics are either not invariant to changes in the general population mortality or are not robust. Standardized statistics and estimators are developed to address the deficiencies. They use a reference distribution for covariates such as age, and a reference population mortality survival distribution that is recommended to approach zero with increasing age as fast as the cohort with the worst life expectancy. Estimators are compared using a breast-cancer survival example and computer simulation. The proposals are invariant and robust, and out-perform current methods to standardize the Ederer II and Pohar-Perme estimators in simulations, particularly for extended follow up. PMID- 27554304 TI - Treating reading comprehension deficits in sub-acute brain injury rehabilitation: Identifying clinical practice and management. AB - There is limited evidence for cognitive-communication reading comprehension (CCRC) interventions for adults following acquired brain injury (ABI), particularly during sub-acute rehabilitation. The purpose of this study was to investigate the clinical practice of speech-language pathologists (SLPs) with CCRC deficits during sub-acute ABI rehabilitation and compare it to the best available evidence. An electronic survey was used to gather information from clinicians across Australia regarding clinical practice in the areas of assessment, intervention, treatment hierarchies and service delivery; survey questions were developed from an extensive review of the literature and expert clinician opinion. Survey findings were then compared with the literature in the form of a systematic review. Surveyed clinicians provided multiple interventions for CCRC rehabilitation, including impairment based (94.7%), activity based (94.7%) and reading strategy interventions (100.0%). Five strategies were used by >94% of SLPs (highlighting, identifying main points/wh- questioning, re-reading, summarising, reducing visual load). When compared with the literature, strong similarities were found for strategy-based interventions and individual service delivery, with broad similarities for functional and impairment-based interventions, and impairment based treatment hierarchies. Strong differences in assessment were identified. Strategy use reported in clinical practice (100.0% SLPs) was higher than in the literature. Further investigation into the effectiveness of specific reading strategies for people with ABI is warranted. PMID- 27554305 TI - Expanded Endonasal Endoscopic Approach for Resection of an Infrasellar Craniopharyngioma. AB - BACKGROUND: Craniopharyngiomas are uncommon benign locally aggressive epithelial tumors mostly located in the sellar and suprasellar regions. An infrasellar origin of these tumors is rare. CASE DESCRIPTION: The authors report a 22-year old male patient with a purely infrasellar adamantinomatous craniopharyngioma centered in the nasopharynx with extension into the posterior nasal septum, sphenoid sinus, and clivus. Gross total resection was achieved using an expanded endonasal endoscopic transethmoidal, transsphenoidal, transpterygoid, and transclival approach. Follow-up at one year demonstrated no evidence of disease recurrence. CONCLUSIONS: Infrasellar craniopharyngioma should be included in the differential diagnosis of sinonasal masses even in the absence of sellar extension. Expanded endonasal endoscopic approaches provide excellent access to and visualization of such lesions and may obviate the need for postoperative radiotherapy when gross total resection is achieved. PMID- 27554306 TI - Perifascial Areolar Tissue Graft for Spinal Dural Repair with Cerebrospinal Fluid Leakage: Case Report of Novel Graft Material, Radiological Assessment Technique, and Rare Postoperative Hydrocephalus. AB - BACKGROUND: Incidental durotomy is a relatively common complication in spinal surgeries, and treatment of persistent cerebrospinal fluid (CSF) leakage is still challenging, especially in cases for which "watertight" suturing is inapplicable. The usefulness of a nonvascularized perifascial areolar tissue (PAT) graft recently was emphasized for plastic and skull base surgeries. Its hypervascularity allows for early engraftment and long-term survival, and its flexibility is advantageous in fixing defects of complex shapes in limited surgical spaces. CASE DESCRIPTION: The authors report a case of persistent CSF leakage after cervical spine surgery in which a PAT graft was used successfully for direct closure of the dural defect. The noninvasive, spin-labeled magnetic resonance imaging technique was used for postoperative assessment of CSF dynamics, not for CSF accumulation but for CSF leakage itself. In addition, some potential causes for the rare development of communicating hydrocephalus after cervical laminoplasty, as seen in this case, are discussed. CONCLUSIONS: PAT was used successfully as an alternative free graft material for direct spinal dural closure, and its hypervascularity seemed to assist with rapid resolution of CSF leakage in our case. Spin-labeled magnetic resonance imaging may enable assessment of spinal CSF dynamics without invasion. PMID- 27554307 TI - Intramedullary Spinal Cord Germinoma: A Case Report and Review of Literature. AB - Primary spinal cord germinomas are an extremely rare group of tumors, most commonly reported as single cases in young Japanese adults. They usually present as intramedullary lesions located in the thoracic and thoracolumbar spine. The importance of preoperative diagnosis lies in the fact that by using radiotherapy and chemotherapy, even without surgery, a good cure rate can be achieved in patients with spinal cord germinoma. These tumors, however, demonstrate unspecific imaging characteristics, and only some secrete tumor markers. Therefore, a diagnosis of these lesions before biopsy or resection with pathohistologic examination can be difficult. We present a case of a 28-year-old white man with intramedullary spinal cord germinoma. The tumor was resected completely with electrophysiological monitoring, without a biopsy and frozen section analysis. Postoperative radiotherapy also was part of the treatment. The patient has had no relapse 4.5 years after diagnosis; however, significant neurologic deficits remain. Although not as frequent in white patients, germinoma should be considered as differential diagnosis in cases of young adult patients with intramedullary tumor in the thoracic or thoracolumbar spine. Therefore, spinal mass surgery should commence with a biopsy and intraoperative frozen section analysis. In this way, attempting a gross total resection becomes unnecessary. With an approach of intraoperative biopsy and frozen section analysis, a considerable amount of postoperative neurologic deficits can be reduced. PMID- 27554308 TI - Endoscopic Histologic Mapping of a Mixed Germ Pineal Tumor. AB - BACKGROUND: The accurate histologic diagnosis of germ cell tumors in the pineal region is a keystone for determining the best treatment strategy and prognosis. This situation poses a challenge for the neuropathologist, considering the lack of a standarized procedure to obtain biopsy samples, which results in few and small specimens, which are not suitable for diagnosis. CASE DESCRIPTION: We report a case in which a pineal region mixed germ cell tumor was accurately diagnosed by performing histologic mapping through a dual burr-hole endoscopic approach. The technical pitfalls and other considerations necessary for obtaining an accurate diagnosis in this tumor subgroup are specified. In addition, the histologic analysis regarding the sampling technique used is described. CONCLUSIONS: The supraorbital frontal endoscopic approach enables the surgeon to perform histologic mapping of pineal region tumors, allowing standarization of the procedure used to obtain the specimens. This approach could result in a more accurate diagnosis, especially in mixed germ cell neoplasms. PMID- 27554309 TI - Difference in Angiographic Characteristics Between Hemorrhagic And Nonhemorrhagic Hemispheres Associated with Hemorrhage Risk of Moyamoya Disease in Adults: A Self Controlled Study. AB - BACKGROUND: Here, we compare the angiographic characteristics of hemorrhagic and nonhemorrhagic hemispheres within the same adult patient with moyamoya disease (MMD) and identify the possible risk factors for initial and recurrent hemorrhage during the long-term follow-up period. METHODS: We retrospectively collected and analyzed the clinical and angiographic data of 145 consecutive adults with hemorrhagic MMD between 2004 and 2011. Separate angiographic characteristics of the hemorrhagic and nonhemorrhagic hemispheres were analyzed based on digital subtraction angiography. Multivariate logistic regression analysis was used to study the risk factors related to initial hemorrhage. In addition, clinical follow-up for at least 5 years was obtained in all the 145 patients. Cox regression analysis was used to determine the predictors for the subsequent recurrent hemorrhagic strokes. RESULTS: With regard to the 145 consecutive patients in our cohort, multivariate analysis indicated that the dilation grade of anterior choroidal artery (odds ratio [OR], 2.449; 95% confidence interval [CI], 1.617-3.862), the dilation grade of the posterior communicating artery (PComA) (OR, 1.491; 95% CI, 1.071-2.075), and the involvement of the posterior cerebral artery (OR, 4.623; 95% CI, 1.273-16.792) were significantly associated with initial hemorrhage. After a median follow-up of 6.33 +/- 1.81 years, 20 of the 145 patients (13.8%) developed 22 recurrent episodes of hemorrhage. No significant correlation was found between rebleeding and the above significant factors associated with the initial hemorrhage. CONCLUSIONS: Compared with the nonhemorrhagic hemispheres, hemorrhagic hemispheres are more prone to recurrent hemorrhage. Our case-control study showed the dilation of the anterior choroidal artery or posterior communicating artery, as well as the involvement of the posterior cerebral artery, is associated with the initial hemorrhage of MMD, but not for the episode of recurrent hemorrhage. Longer and more detailed clinical and angiographic follow-up are still needed to delineate the specific mechanism underlying the recurrent hemorrhage in hemorrhagic MMD. PMID- 27554310 TI - A case-matched study of neurophysiological correlates to attention/working memory in people with somatic hypervigilance. AB - OBJECTIVE: Somatic hypervigilance describes a clinical presentation in which people report more, and more intense, bodily sensations than is usual. Most explanations of somatic hypervigilance implicate altered information processing, but strong empirical data are lacking. Attention and working memory are critical for information processing, and we aimed to evaluate brain activity during attention/working memory tasks in people with and without somatic hypervigilance. METHOD: Data from 173 people with somatic hypervigilance and 173 controls matched for age, gender, handedness, and years of education were analyzed. Event-related potential (ERP) data, extracted from the continuous electroencephalograph recordings obtained during performance of the Auditory Oddball task, and the Two In A Row (TIAR) task, for N1, P2, N2, and P3, were used in the analysis. Between group differences for P3 amplitude and N2 amplitude and latency were assessed with two-tailed independent t tests. Between-group differences for N1 and P2 amplitude and latency were assessed using mixed, repeated measures analyses of variance (ANOVAs) with group and Group * Site factors. Linear regression analysis investigated the relationship between anxiety and depression and any outcomes of significance. RESULTS: People with somatic hypervigilance showed smaller P3 amplitudes-Auditory Oddball task: t(285) = 2.32, 95% confidence interval, CI [3.48, 4.47], p = .026, d = 0.27; Two-In-A-Row (TIAR) task: t(334) = 2.23, 95% CI [2.20; 3.95], p = .021, d = 0.24-than case-matched controls. N2 amplitude was also smaller in people with somatic hypervigilance-TIAR task: t(318) = 2.58, 95% CI [0.33, 2.47], p = .010, d = 0.29-than in case-matched controls. Neither depression nor anxiety was significantly associated with any outcome. CONCLUSION: People with somatic hypervigilance demonstrated an event-related potential response to attention/working memory tasks that is consistent with altered information processing. PMID- 27554311 TI - Central natriuretic peptide receptor (NPR)-B and peripheral lipid accumulation. PMID- 27554312 TI - Baseline Frailty Evaluation in Drug Development. PMID- 27554322 TI - Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair. AB - Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34-CD45-CD146+) and adventitial cells (CD34+CD45-CD146-). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair. PMID- 27554323 TI - Measuring Risk Perception in Later Life: The Perceived Risk Scale. AB - BACKGROUND: Risk perception is a subjective assessment of the actual or potential threat to one's life or, more broadly, to one's psychological well-being. Given the various risks associated with later life, a valid and reliable integrative screening tool for assessing risk perception among the elderly is warranted. OBJECTIVES: The study examined the psychometric properties and factor structure of a new integrative risk perception instrument, the Perceived Risk Scale. This eight-item measure refers to various risks simultaneously, including terror, health issues, traffic accidents, violence, and financial loss, and was developed specifically for older adults. DESIGN: An online survey was conducted with 306 participants aged 50 years and older. The scale was examined using exploratory factor analysis and concurrent validity testing. RESULTS: Factor analysis revealed a two-factor structure: later-life risks and terror risks A high percentage of explained variance, as well as internal consistency, was found for the entire scale and for both factors. Concurrent validity was supported by significant positive associations with participants' depression and negative correlations with their life satisfaction. CONCLUSION: These findings suggest that the Perceived Risk Scale is internally reliable, valid, and appropriate for evaluating risk perception in later life. The scale's potential applications are discussed. PMID- 27554325 TI - Computational Approaches to the Chemical Equilibrium Constant in Protein-ligand Binding. AB - The physiological role played by protein-ligand recognition has motivated the development of several computational approaches to the ligand binding affinity. Some of them, termed rigorous, have a strong theoretical foundation but involve too much computation to be generally useful. Some others alleviate the computational burden by introducing strong approximations and/or empirical calibrations, which also limit their general use. Most importantly, there is no straightforward correlation between the predictive power and the level of approximation introduced. Here, we present a general framework for the quantitative interpretation of protein-ligand binding based on statistical mechanics. Within this framework, we re-derive self-consistently the fundamental equations of some popular approaches to the binding constant and pinpoint the inherent approximations. Our analysis represents a first step towards the development of variants with optimum accuracy/efficiency ratio for each stage of the drug discovery pipeline. PMID- 27554324 TI - Polygonatum sibiricum polysaccharide inhibits osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through Wnt/beta-catenin signalling pathway. AB - Bone homeostasis is maintained by a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis occurs when osteoclast activity surpasses osteoblast activity. Our previous studies showed the plant-derived natural polysaccharide (Polygonatum sibiricum polysaccharide or PSP) had significant anti-ovariectomy (OVX)-induced osteoporosis effects in vivo, but the mechanisms of PSP's anti-osteoporosis effect remains unclear. In this study, we assessed PSP's effect on the generation of osteoblast and osteoclast in vitro. This study showed that PSP promoted the osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) without affecting BMPs signaling pathway. This effect was due to the increased nuclear accumulation of beta-catenin, resulting in a higher expression of osteoblast-related genes. Furthermore, the study showed PSP could inhibit the receptor activator of nuclear factor-kappaB ligand (RANKL) induced osteoclastogenesis and exert prophylatic protection against LPS-induced osteolysis in vivo. This effect was also related to the increased nuclear accumulation of beta-catenin, resulting in the decreased expression of osteoclast related genes. In conclusion, our results showed that PSP effectively promoted the osteogenic differentiation of mouse BMSCs and suppressed osteoclastogenesis; therefore, it could be used to treat osteoporosis. PMID- 27554326 TI - Quantitative profiling of spreading-coupled protein tyrosine phosphorylation in migratory cells. AB - Protein tyrosine phosphorylation is an important mechanism that regulates cytoskeleton reorganization and cell spreading of migratory cells. A number of cytoskeletal proteins are known to be tyrosine phosphorylated (pY) in different cellular processes. However, the profile of pY proteins during different stages of cell spreading has not been available. Using immunoafffinity enrichment of pY proteins coupled with label free quantitative proteomics, we quantitatively identified 447 pY proteins in the migratory ECV-304 cells at the early spreading (adhesion) and the active spreading stages. We found that pY levels of the majority of the quantified proteins were significantly increased in the active spreading stage compared with the early spreading stage, suggesting that active cell spreading is concomitant with extra tyrosine phosphorylation. The major categories of proteins impacted by tyrosine phosphorylation are involved in cytoskeleton and focal adhesion regulation, protein translation and degradation. Our findings, for the first time, dissect the cell spreading-specific pY signals from the adhesion induced pY signals, and provide a valuable resource for the future mechanistic research regarding the regulation of cell spreading. PMID- 27554328 TI - Association of IL12B Gene Polymorphisms with Rheumatoid Arthritis: A Meta analysis. PMID- 27554327 TI - Scoping review: strategies of providing care for children with chronic health conditions in low- and middle-income countries. AB - OBJECTIVES: To identify and review strategies of providing care for children living with chronic health conditions in low- and middle-income countries. METHODS: We searched MEDLINE and Cochrane EPOC databases for papers evaluating strategies of providing care for children with chronic health conditions in low- or middle-income countries. Data were systematically extracted using a standardised data charting form, and analysed according to Arksey and O'Malley's 'descriptive analytical method' for scoping reviews. RESULTS: Our search identified 71 papers addressing eight chronic conditions; two chronic communicable diseases (HIV and TB) accounted for the majority of papers (n = 37, 52%). Nine (13%) papers reported the use of a package of care provision strategies (mostly related to HIV and/or TB in sub-Saharan Africa). Most papers addressed a narrow aspect of clinical care provision, such as patient education (n = 23) or task-shifting (n = 15). Few papers addressed the strategies for providing care at the community (n = 10, 15%) or policy (n = 6, 9%) level. Low income countries were under-represented (n = 24, 34%), almost exclusively involving HIV interventions in sub-Saharan Africa (n = 21). Strategies and summary findings are described and components of future models of care proposed. CONCLUSIONS: Strategies that have been effective in reducing child mortality globally are unlikely to adequately address the needs of children with chronic health conditions in low- and middle-income settings. Current evidence mostly relates to disease-specific, narrow strategies, and more research is required to develop and evaluate the integrated models of care, which may be effective in improving the outcomes for these children. PMID- 27554329 TI - Nuclear Transcription Factor Kappa B Downregulation Reduces Chemoresistance in Bone Marrow-derived Cells Through P-glycoprotein Modulation. PMID- 27554330 TI - V-Y advancement flaps for extensive perianal defect repair. AB - OBJECTIVES: Some perianal pathologies require aggressive surgery that will need techniques to allow to re-establish the integrity of the perianal region. The purpose is to analyze short and long term results after perineal reconstruction with V-Y flaps. METHODS: A retrospective review of prospectively collected database was conducted at Virgen de la Arrixaca's Hospital in Murcia (Espana) between January 2000 and December 2013. The study includes all patients who underwent a perineal reconstruction with V-Y flaps. Demographic and surgical data and short-/long- term morbidity was recorded. RESULTS: 10 patients were included, 6 males and 4 females. The average age was 58,1+/-17,4 years. Surgical indication included both malignant and benign pathologies. Operating time was 143,5+/ 41,3min. R0 resection was performed in all cases although histopathological analysis showed involvement of the deeper margin in 3 cases. Length of hospital stay was 7,8+/-7,6 days. Regarding complications: 6 patients had partial dehiscence of the flap. None of the patients lost the flap completely. The most frequent late complication was anal stenosis (n=4). Follow up showed total continence in 7 patients. Two patients had variable fecal and/or flatus incontinence. A colostomy was made in one case due to severe incontinence. CONCLUSIONS: V-Y flaps are an effective and feasible technique to cover large perianal defects after aggressive surgeries. However, this technique is not free of postoperative morbidity. PMID- 27554331 TI - Anaesthetic management of breast surgery in a patient with Eisenmenger syndrome. AB - Eisenmenger syndrome (ES) is a complex combination of cardiovascular abnormalities defined as pulmonary hypertension with investment or bidirectional flow through an intracardiac or aortopulmonary communication, usually secondary to a congenital heart disease not resolved promptly. It carries a significant risk of perioperative mortality, with an incidence close to 30% for non-cardiac surgery. We report the anaesthetic management in a ES patient undergoing breast surgery, which was successfully performed under general anaesthesia combined with thoracic analgesic blocks. The main pathophysiological implications of this syndrome are discussed, emphasizing the importance of appropriate preoperative evaluation with thorough assessment of associated risks, careful intraoperative management, and postoperative care, which should be initially performed in a critical care unit. The need to individualize and tailor the choice of drugs and anesthetic technique to the hemodynamic condition of the patient and the surgical procedure is highlighted. PMID- 27554332 TI - Epidural anesthesia and analgesia in liver resection: Safety and effectiveness. AB - OBJECTIVES: Perioperative epidural analgesia in liver resection provides optimal dynamic pain relief. Coagulation disorders occurring in the postoperative period can lead to greater risk of complications during epidural catheter removal. The aim of this study is to evaluate the effectiveness and complications of epidural analgesia and delayed epidural catheter removal due to postoperative coagulopathy. METHODS: A retrospective study of 114 patients undergoing open liver resection and epidural analgesia, from March 2012 to February 2015. Postoperative course of pain intensity, coagulation parameters and delayed catheter removal was analyzed RESULTS: Of the 114 operated patients, 73 met the inclusion criteria. 59% of patients received major hepatectomy (resection >= 3 segments) and 15% had Child's Class A cirrhosis (11/73). 96% of catheters functioned properly. 89% of patients had controlled pain (numerical rate scale <3) at rest and 8.2% (6 patients) had severe pain (numerical rate scale > 6) with movement. The INR peaked on postoperative day 2, 1.41 [0.99-2.30], and gradually returned to normal values in most patients by postoperative day 4, 1.26 [0.90 - 2.20]. The catheters were left in place 3.6 (+/- 1.1) days. In 6 patients (8%), catheter removal was postponed due to coagulation disorders. CONCLUSIONS: Epidural analgesia for liver resection was a safe practice, which produced optimal control of postoperative pain. The percentage of delayed catheter removal due to postoperative coagulopathy was low, not requiring transfusion of blood products. PMID- 27554333 TI - Paper-Origami-Based Multiplexed Malaria Diagnostics from Whole Blood. AB - We demonstrate, for the first time, the multiplexed determination of microbial species from whole blood using the paper-folding technique of origami to enable the sequential steps of DNA extraction, loop-mediated isothermal amplification (LAMP), and array-based fluorescence detection. A low-cost handheld flashlight reveals the presence of the final DNA amplicon to the naked eye, providing a "sample-to-answer" diagnosis from a finger-prick volume of human blood, within 45 min, with minimal user intervention. To demonstrate the method, we showed the identification of three species of Plasmodium, analyzing 80 patient samples benchmarked against the gold-standard polymerase chain reaction (PCR) assay in an operator-blinded study. We also show that the test retains its diagnostic accuracy when using stored or fixed reference samples. PMID- 27554334 TI - Stigma Experiences in Marginalized People Living With HIV Seeking Health Services and Resources in Canada. AB - HIV stigma may prevent people from obtaining a timely diagnosis and engaging in life-saving care. It may also prevent those who are HIV infected from seeking health and education resources, particularly if they are from marginalized communities. We inductively explored the roots of stigma and its impact on health services and resource seeking as experienced by HIV-infected members of marginalized communities in Vancouver, British Columbia, Canada, using a community-based participatory research framework. Five peer-facilitated focus groups were conducted with 33 Aboriginal, Latino, Asian, and African participants. Thematic analysis of the experiences revealed four dominant themes: beginnings of stigma, tensions related to disclosure, experiences of service seeking, and beyond HIV stigma and discrimination. Persons living with HIV from Aboriginal and refugee communities continue to experience disproportionate rates of stigma and discrimination. Fear remains a prime obstacle influencing these groups' abilities and willingness to access care in various settings. PMID- 27554335 TI - DC-SIGN promotes allergen uptake and activation of dendritic cells in patients with atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease, concomitant with allergic reactions to allergens. However, the exact mechanisms of allergen-induced immune responses in AD are not clear. The aim of this study is to explore the role of DC-SIGN in capturing and processing glycan-containing allergens and in the subsequent DC activation and T helper cell polarization in AD patients. METHODS: DC-SIGN expression on DCs from AD patients was analysed by confocal microscopy and flow cytometry. DC-SIGN binding to common allergens was determined by ELISA. Activation of monocyte-derived dendritic cells (Mo-DCs) by allergens was analysed by evaluation of pro-inflammatory cytokines production, and their impact on T-cell responses was investigated by a DC-T cell coculture. RESULTS: DC-SIGN expression was higher on DCs in the lesional skin of AD patients compared with that of healthy controls and was correlated with disease severity. DC-SIGN could bind to many common allergens including house dust mite allergen (Der p2) and egg white allergen (Gal d2). Mo-DCs showed measurable expression of DC-SIGN and a concentration-dependent uptake of Der p2 and Gal d2, which was inhibited by mannan and anti-DC-SIGN Abs. Der p2 and Gal d2 induced the production of pro-inflammatory cytokines, including TNF-alpha and IL-6, by DCs from AD patients and facilitated Th2 and Th22 cell polarization. CONCLUSIONS: Binding of common allergens by DC-SIGN on DCs may initiate allergen sensitization of AD or provoke the relapse of AD. Regulating the allergen-DC-SIGN interaction might be a promising strategy to prevent or intervene in the progress of AD. PMID- 27554336 TI - Whole-exome sequencing confirmation of multiple MC1R variants associated with extensive freckles and red hair: Analysis of a Mongolian family. PMID- 27554337 TI - Ectodermal dysplasia-skin fragility syndrome resulting from a new atypical homozygous cryptic acceptor splice site mutation in PKP1. PMID- 27554338 TI - Combination of oral zinc gluconate and topical triclosan: An anti-inflammatory treatment modality for initial hidradenitis suppurativa. AB - BACKGROUND: Hidradenitis suppurativa (HS) is often a therapeutic challenge with relapses and chronicity which can severely impact patients' quality of life. OBJECTIVE: To evaluate the efficacy of anti-inflammatory oral zinc gluconate, 90mg/day, combined with topical triclosan, 2% twice daily. METHODS: We retrospectively evaluated the medical records of HS patients in our HS Center of the Department of Dermatology, Venereology, and Allergology, Ruhr-University Bochum, regarding change of disease severity and quality of life. Secondary outcome measures were the number of nodules and fistulas, the number of boils or flair-ups, and the intensity of pain. RESULTS: Sixty-six patients in Hurley stage I and II were included. After 3 months of combination therapy, the modified HS Score and the Dermatology Life Quality Index improved significantly (p<0.0001 and p=0.0386, respectively). The number of inflammatory nodules, new boils or flare ups, and erythema scores decreased significantly. Fistula count and the visual analogue scale score showed no significant difference. Side-effects (mostly abdominal pain and nausea) were reported by 12 (22.2%) patients. CONCLUSION: The combination therapy of zinc gluconate and topical triclosan can be considered as an anti-inflammatory treatment for HS patients in Hurley stage I and initial Hurley stage II. PMID- 27554339 TI - ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells. AB - ADAMs are transmembrane multifunctional proteins that contain disintegrin and metalloprotease domains. ADAMs act in a diverse set of biological processes, including fertilization, inflammatory responses, myogenesis, cell migration, cell proliferation and ectodomain cleavage of membrane proteins. These proteins also have additional functions in pathological processes as cancer and metastasis development. ADAM9 is a member of ADAM protein family that is overexpressed in several types of human carcinomas. The aim of this study was to investigate the role of ADAM9 in hematogenous and lymphatic tumor cell dissemination assisting the development of new therapeutic tools. The role of ADAM9 in the interaction of breast tumor cells (MDA-MB-231) and endothelial cells was studied through RNA silencing. ADAM9 silencing in MDA-MB-231 cells had no influence in expression of several genes related to the metastatic process such as ADAM10, ADAM12, ADAM17, cMYC, MMP9, VEGF-A, VEGF-C, osteopontin and collagen XVII. However, there was a minor decrease in ADAM15 expression but an increase in that of MMP2. Moreover, ADAM9 silencing had no effect in the adhesion of MDA-MB-231 cells to vascular (HMEC-1 and HUVEC) and lymphatic cells (HMVEC-dLyNeo) under flow condition. Nevertheless, siADAM9 in MDA-MB-231 decreased transendothelial cell migration in vitro through HUVEC, HMEC-1 and HMVEC-dLyNeo (50%, 40% and 32% respectively). These results suggest a role for ADAM9 on the extravasation step of the metastatic cascade through both blood and lymph vessels. PMID- 27554340 TI - Blockage of Galectin-receptor Interactions by alpha-lactose Exacerbates Plasmodium berghei-induced Pulmonary Immunopathology. AB - Malaria-associated acute lung injury (ALI) is a frequent complication of severe malaria that is often caused by "excessive" immune responses. To better understand the mechanism of ALI in malaria infection, here we investigated the roles of galectin (Gal)-1, 3, 8, 9 and the receptors of Gal-9 (Tim-3, CD44, CD137, and PDI) in malaria-induced ALI. We injected alpha (alpha)-lactose into mice-infected with Plasmodium berghei ANKA (PbANKA) to block galectins and found significantly elevated total proteins in bronchoalveolar lavage fluid, higher parasitemia and tissue parasite burden, and increased numbers of CD68(+) alveolar macrophages as well as apoptotic cells in the lungs after blockage. Additionally, mRNA levels of Gal-9, Tim-3, CD44, CD137, and PDI were significantly increased in the lungs at day 5 after infection, and the levels of CD137, IFN-alpha, IFN-beta, IFN-gamma, IL-4, and IL-10 in the lungs were also increased after alpha-lactose treatment. Similarly, the levels of Gal-9, Tim-3, IFN-alpha, IFN-beta, IFN-gamma, and IL-10 were all significantly increased in murine peritoneal macrophages co cultured with PbANKA-infected red blood cells in vitro; but only IFN-alpha and IFN-beta were significantly increased after alpha-lactose treatment. Our data indicate that Gal-9 interaction with its multiple receptors play an important role in murine malaria-associated ALI. PMID- 27554341 TI - Mesenchymal Stem Cells Reversed Morphine Tolerance and Opioid-induced Hyperalgesia. AB - More than 240 million opioid prescriptions are dispensed annually to treat pain in the US. The use of opioids is commonly associated with opioid tolerance (OT) and opioid-induced hyperalgesia (OIH), which limit efficacy and compromise safety. The dearth of effective way to prevent or treat OT and OIH is a major medical challenge. We hypothesized that mesenchymal stem cells (MSCs) attenuate OT and OIH in rats and mice based on the understanding that MSCs possess remarkable anti-inflammatory properties and that both OT and chronic pain are associated with neuroinflammation in the spinal cord. We found that the development of OT and OIH was effectively prevented by either intravenous or intrathecal MSC transplantation (MSC-TP), which was performed before morphine treatment. Remarkably, established OT and OIH were significantly reversed by either intravenous or intrathecal MSCs when cells were transplanted after repeated morphine injections. The animals did not show any abnormality in vital organs or functions. Immunohistochemistry revealed that the treatments significantly reduced activation level of microglia and astrocytes in the spinal cord. We have thus demonstrated that MSC-TP promises to be a potentially safe and effective way to prevent and reverse two of the major problems of opioid therapy. PMID- 27554342 TI - Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging. AB - Stable heavy isotopes co-exist with their lighter counterparts in all elements commonly found in biology. These heavy isotopes represent a low natural abundance in isotopic composition but impose great retardation effects in chemical reactions because of kinetic isotopic effects (KIEs). Previous isotope analyses have recorded pervasive enrichment or depletion of heavy isotopes in various organisms, strongly supporting the capability of biological systems to distinguish different isotopes. This capability has recently been found to lead to general decline of heavy isotopes in metabolites during yeast aging. Conversely, supplementing heavy isotopes in growth medium promotes longevity. Whether this observation prevails in other organisms is not known, but it potentially bears promise in promoting human longevity. PMID- 27554343 TI - The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations. AB - OBJECTIVE: The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability.1 Individuals with loss-of-function mutations in SHANK3 have intellectual disability, autism, and variably, epilepsy.2-5 The spectrum of seizure semiologies and electroencephalography (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately 2% of individuals with moderate to severe intellectual disabilities and 1% of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations. METHODS: A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss-of-function mutation in SHANK3 identified through whole-exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset, and efficacy of therapy were determined. Electroencephalography studies were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist. RESULTS: There is a wide spectrum of seizure semiologies, frequencies, and severity in individuals with SHANK3 mutations. There are no specific EEG abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure. SIGNIFICANCE: All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure, which can be challenging to identify due to comorbid intellectual disability in individuals with SHANK3 mutations; however, no consistent seizure semiology, neuroimaging findings, or EEG findings were present in the majority of individuals with SHANK3 mutations. PMID- 27554345 TI - Abstracts for EUROSPINE Meeting 2016 Berlin, Germany, October 5-7. PMID- 27554344 TI - Nitrogen fixation and nifH diversity in human gut microbiota. AB - It has been hypothesized that nitrogen fixation occurs in the human gut. However, whether the gut microbiota truly has this potential remains unclear. We investigated the nitrogen-fixing activity and diversity of the nitrogenase reductase (NifH) genes in the faecal microbiota of humans, focusing on Papua New Guinean and Japanese individuals with low to high habitual nitrogen intake. A (15)N2 incorporation assay showed significant enrichment of (15)N in all faecal samples, irrespective of the host nitrogen intake, which was also supported by an acetylene reduction assay. The fixed nitrogen corresponded to 0.01% of the standard nitrogen requirement for humans, although our data implied that the contribution in the gut in vivo might be higher than this value. The nifH genes recovered in cloning and metagenomic analyses were classified in two clusters: one comprising sequences almost identical to Klebsiella sequences and the other related to sequences of Clostridiales members. These results are consistent with an analysis of databases of faecal metagenomes from other human populations. Collectively, the human gut microbiota has a potential for nitrogen fixation, which may be attributable to Klebsiella and Clostridiales strains, although no evidence was found that the nitrogen-fixing activity substantially contributes to the host nitrogen balance. PMID- 27554346 TI - Solitary bone cyst of a lumbar vertebra treated with percutaneous steroid injection: a case report and review of literature. AB - PURPOSE: We describe a rare case of solitary bone cyst involving the vertebral body of L4. INTRODUCTION: To the best of the authors' knowledge, only 15 cases of solitary bone cysts involving the spine have been reported previously. All the reported cases were treated surgically, including resection and curettage with or without bone grafting. In the current case, treatment was with steroid injection alone. METHOD: A cystic lesion involving the vertebral body of L4 was identified in a 16-year-old girl with persistent low back pain of 2 years' duration. According to the radiological characteristics of the lesion, a diagnosis of solitary bone cyst was suspected. The patient underwent surgical intervention with percutaneous steroid injection alone since there was no evidence of thinned cortex or pathological fracture. The patient was discharged 2 days after this intervention with resolution of the low back pain. RESULT: At the final follow-up 7 months after treatment, the patient was asymptomatic and the beginning of bony healing was evident. CONCLUSION: Herein, we reported an extremely rare case of solitary bone cyst involving the body of the fourth lumbar vertebra. Local steroid injection should be considered as a minimally invasive intervention for a solitary bone cyst involving the spinal column with no evidence of thinned cortex or pathological fracture. PMID- 27554347 TI - Transcranial magnetic stimulation in the semi-quantitative, pre-operative assessment of patients undergoing spinal deformity surgery. AB - PURPOSE: To compare measurements of motor evoked potential latency stimulated either magnetically (mMEP) or electrically (eMEP) and central motor conduction time (CMCT) made pre-operatively in conscious patients using transcranial and intra-operatively using electrical cortical stimulation before and after successful instrumentation for the treatment of adolescent idiopathic scoliosis. METHODS: A group initially of 51 patients with adolescent idiopathic scoliosis aged 12-19 years was evaluated pre-operatively in the outpatients' department with transcranial magnetic stimulation. The neurophysiological data were then compared statistically with intra-operative responses elicited by transcranial electrical stimulation both before and after successful surgical intervention. MEPs were measured as the cortically evoked compound action potentials of Abductor hallucis. Minimum F-waves were measured using conventional nerve conduction methods and the lower motor neuron conduction time was calculated and this was subtracted from MEP latency to give CMCT. RESULTS: Pre-operative testing was well tolerated in our paediatric/adolescent patients. No neurological injury occurred in any patient in this series. There was no significant difference in the values of mMEP and eMEP latencies seen pre-operatively in conscious patients and intra-operatively in patients under anaesthetic. The calculated quantities mCMCT and eCMCT showed the same statistical correlations as the quantities mMEP and eMEP latency. CONCLUSIONS: The congruency of mMEP and eMEP and of mCMCT and eCMCT suggests that these measurements may be used comparatively and semi quantitatively for the comparison of pre-, intra-, and post-operative spinal cord function in spinal deformity surgery. PMID- 27554348 TI - Anatomical variations of the foramen transversarium in cervical vertebrae: findings, review of the literature, and clinical significance during cervical spine surgery. AB - PURPOSE: To describe certain anatomical variations of the foramen transversarium, in spine cervical vertebrae in a contemporary specimen of an Indo-European population and approach their clinical importance during cervical spine surgery. METHODS: 102 cervical vertebrae (C2-C7) from 17 different skeletons, intact without any degenerative or traumatic disorders, which belonged to the collection of the Department of Anatomy, were examined. The age of specimens at the time of their death was between 25 and 65 years. All foramina were measured with a digital caliper. RESULTS: The average size of the normal foramina was: 6.49 mm * 5.74 mm on the right side and 6.65 mm * 5.76 mm on the left side. Regarding the variations, we found two cervical vertebrae (1.96 %), one C3 and one C6, in which the right foramen transversarium is clearly smaller than the left. The exact dimensions of these foramina are: 2.3 mm * 2.5 mm on the right side and 6.54 mm * 8 mm on the left side in the first vertebra and 2.8 mm * 3.74 mm on the right side and 6 mm * 7.5 mm on the left side, in the second one. We also observed double foramina in 14 vertebrae (13.72 %). In seven vertebrae, the duplication was bilateral (6.86 %). We finally found one vertebra (0.98 %) with triplication of the foramen transversarium on the left side. CONCLUSIONS: Summarizing, 10 out of our 17 skeletons were presented with variations (extremely narrow or multiple foramina). This finding of hypoplastic, duplicated and triplicated foramina transversaria in unexpectedly high rates raises questions about the integrity of the contained structures, the possibility of a different path for them. These variations may induce an extra-osseous position of the vertebra artery, and the ignorance of such an event may have catastrophic consequences during a surgery in the cervical spine. PMID- 27554349 TI - The changes of syrinx volume after posterior reduction and fixation of basilar invagination and atlantoaxial dislocation with syringomyelia. AB - PURPOSE: The purpose of this study focuses on the changes of the syrinx volume after posterior reduction and fixation of the basilar invagination (BI) and atlantoaxial dislocation (AAD) with syringomyelia. METHODS: We retrospectively analyzed the clinical outcome and syrinx volume changes in 71 patients with BI, AAD and syringomyelia treated with the posterior reduction and fixation technique. RESULTS: Clinical improvement was observed in 64 (90.1 %) patients postoperatively; 5 (7.0 %) were stable and 2 (2.8 %) were clinically aggravated. The postoperative Atlantodental interval became normal in 61 patients (86.0 %); showed reduction that was greater than 50 % but not complete in 5 patients (7.0 %); and reduction which was less than 50 % in 5 patients (7.0 %). The size of the syrinx was reduced postoperatively in 66 patients (93.0 %) while no change in the remaining 5 patients (7.0 %). CONCLUSIONS: Posterior reduction and fixation of the AAD and BI can effectively enlarge the foramen magnum, improve the cerebrospinal fluid circulation and consequently reduce the volume of the syrinx. PMID- 27554350 TI - Association between IGF1 gene single nucleotide polymorphism (rs5742612) and adolescent idiopathic scoliosis: a meta-analysis. AB - PURPOSE: Insulin-like growth factor 1 (IGF1) gene single nucleotide polymorphism (rs5742612) has been associated with adolescent idiopathic scoliosis (AIS) in several studies with limited sample size and inconsistent outcomes. So we perform this meta-analysis to assess the precise association between IGF1 gene single nucleotide polymorphism (rs5742612) and AIS. METHODS: We systematically searched Pubmed, Embase, Web of Science and Cochrane Library up to January 19, 2016 to obtain relevant studies using our research strategy. Four articles all belonging to case-control studies were included in our meta-analysis. RESULTS: A total of four studies containing 763 cases and 559 controls satisfied the inclusion criteria after judgment by two reviewers. No significant associations were detected between IGF1 gene single nucleotide polymorphism (rs5742612) and AIS (T vs. C, OR = 1.10, 95 % CI 0.91-1.34, p = 0.32; TT vs. CC: OR = 1.28, 95 % CI 0.82 2.02, p = 0.28; TC vs. CC: OR = 1.29, 95 % CI 0.82-2.06, p = 0.27; TT/TC vs. CC: OR = 1.28, 95 % CI 0.83-1.98, p = 0.27; TT vs. TC/CC: OR = 1.06, 95 % CI 0.82 1.36, p = 0.66). CONCLUSIONS: IGF1 gene single nucleotide polymorphism (rs5742612) is not significant associated with susceptibility to AIS in either Asian or Caucasian populations. However, IGF1 gene rs5742612 may be associated with severity of AIS. Further studies with larger sample size and different population groups involving the relationship are required to confirm the potential association. PMID- 27554351 TI - Percutaneous pedicle screw fixation plus kyphoplasty for thoracolumbar fractures A2, A3 and B2. AB - DESIGN: Retrospective cohort. PURPOSE: The aim of this study is to evaluate the effectiveness of percutaneous short fixation (PSFx) plus kyphoplasty (BP) for thoracolumbar fractures. METHODS: Thirty-six consecutive selected patients, aged 59 +/- 17 years, with fresh single thoracolumbar A2, A3, and B2 AO-type fracture, received PSFx plus BP. The primary outcomes pain, and vertebral body deformity; and the secondary outcomes screw malposition, facet violation, PMMA leakage, adjacent segment degeneration (ASD) and loss of correction were evaluated. The f/up was 31 +/- 7 months. RESULTS: Pain and kyphosis decreased and vertebral body heights increased significantly postoperation. PMMA leakage occurred in five cases; 6 (4 %) screws were grades III malpositioned in relation to pedicle; facet violation occurred in 8 (5.5 %) facets; loss of kyphosis correction was 3.68 degrees ; ASD occurred in two cases; interfacet fusion in ten (28 %) patients; Three patients were reoperated for different reasons. CONCLUSIONS: PSFx plus BP for thoracolumbar fractures reduces significantly spinal deformity and pain with few complications. PMID- 27554352 TI - Tarlov cysts: long-term follow-up after microsurgical inverted plication and sacroplasty. AB - PURPOSE: Surgical treatment of Tarlov cysts is still a matter of debate. Published literature thus far includes mainly small case series with retrospective evaluation and short-term follow-up. We present a novel microsurgical technique that combines the decompression of the nerve fibers with the prevention of recurrence. The long-term follow-up is provided. METHODS: The indication for surgery was incapacitating pain refractory to medical therapy for at least 6 months. The surgical technique consisted in microsurgical opening of the cyst, relief of CSF followed by secured inverted plication of the cyst wall, packing of remnant space with fat graft, and sacroplasty. Pain and neurological deficits were evaluated according to a modified Barrow National Institute score (BNI score, 0-5) and the Departmental Neuro Score (DNS score, 0-20). RESULTS: A total of 13 patients (9 women, 4 men) were operated and followed up to 14 years (mean FU 5.3 years). Mean age at surgery was 51.8 (+/-14) years. Pain and neurological deficits improved significantly in 11/13 patients (BNI score pre-OP 5 vs 3.1 +/- 1.2 at 1-year-FU, and 2.8 +/- 1.2 at last follow-up visit; DNS score pre-OP 5.5 +/- 1.5 vs 2.8 +/- 2.1 at 1-year follow-up, and 2.6 +/- 2.2 at last follow-up visit. Two patients needed revision surgery due to reoccurrence of the cyst. One patient suffered deterioration of preexisting neurological deficit. CONCLUSIONS: The inverted plication technique combined with sacroplasty is a promising technique. It improves pain and neurological deficits on the long term in the majority of patients with symptomatic Tarlov cysts. PMID- 27554353 TI - A comparison of a new zero-profile, stand-alone Fidji cervical cage and anterior cervical plate for single and multilevel ACDF: a minimum 2-year follow-up study. AB - PURPOSE: To compare perioperative parameters, clinical outcomes, radiographic parameters, and complication rates of the new zero-profile, stand-alone Fidji cervical cage with those of the stand-alone cages with a titanium plate for anterior cervical discectomy and fusion (ACDF) for the surgical treatment of single- and multilevel cervical degenerative disc disease (DDD). METHODS: Between October 2009 and December 2013, 152 consecutive patients [86 males and 52 females; mean age 51.0 years (range 30-69 years)] with cervical DDD, who underwent surgery and were followed for more than 2 years, were enrolled in this study and divided into the cage group and plate group. The study compared perioperative parameters, surgery-related and implant-related complication rates, clinical outcomes, and radiologic parameters. RESULTS: The clinical and radiologic results in both groups were satisfactory after a minimum 2-year follow up. No significant differences between the cage group and plate group in terms of improvement in the 36-Item Short Form Health Survey, visual analogue scale, Neck Disability Index, Japanese Orthopedic Association scores, disc height, mean fusion time, fusion rate, adjacent segment degeneration, and restoration of cervical lordosis, but the cage group was associated with a lower risk of postoperative dysphagia, shorter operation time, less blood loss, less cost of index surgery, and relatively greater simplicity than the plate group. CONCLUSIONS: The zero-profile, stand-alone Fidji cervical cage for ACDF is an effective, reliable, and safe alternate to the conventional method for the treatment of cervical DDD. However, there is no definitive evidence that Fidji cervical cage has better intermediate-term outcomes than the stand-alone cages with a titanium plate for ACDF. PMID- 27554354 TI - Laminoplasty versus laminectomy with fusion for the treatment of spondylotic cervical myelopathy: short-term follow-up. AB - BACKGROUND CONTEXT: Laminoplasty and laminectomy with fusion are two common procedures for the treatment of cervical spondylotic myelopathy. Controversy remains regarding the superior surgical treatment. PURPOSE: To compare short-term follow-up of laminoplasty to laminectomy with fusion for the treatment of cervical spondylotic myelopathy. STUDY DESIGN/SETTING: Retrospective review comparing all patients undergoing surgical treatment for cervical spondylotic myelopathy by a single surgeon. PATIENT SAMPLE: All patients undergoing laminoplasty or laminectomy with fusion by a single surgeon over a 5-year period (2007-2011). OUTCOME MEASURES: Cervical alignment and range of motion on pre- and post-operative radiographs and clinical outcome measures including Japanese Orthopaedic Association (JOA) scores, neck disability index (NDI), short form-12 mental (SF-12M) and physical (SF-12P) composite scores and visual analog pain scores for neck (VAS-N) and arm (VAS-A). METHODS: Patients undergoing laminoplasty or laminectomy with fusion by a single surgeon were reviewed. Cohorts of 41 laminoplasty patients and 31 laminectomy with fusion patients were selected based on strict criteria. The cohorts were well matched based on pre operative clinical scores, radiographic measurements, and demographics. The average follow-up was 19.2 months for laminoplasty and 18.2 months for laminectomy with fusion. Evaluated outcomes included Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), short form-12 (SF-12), visual analog pain scores (VAS), cervical sagittal alignment, cervical range of motion, length of stay, cost and complications. RESULTS: The improvement in JOA, SF-12 and VAS scores was similar in the two cohorts after surgery. There was no significant change in cervical sagittal alignment in either cohort. Range-of motion decreased in both cohorts, but to a greater degree after laminectomy with fusion. C5 nerve root palsy and infection were the most common complications in both cohorts. Laminectomy with fusion was associated with a higher rate of C5 nerve root palsy and overall complications. The average hospital length of stay and cost were significantly less with laminoplasty. CONCLUSIONS: This study provides evidence that laminoplasty may be superior to laminectomy with fusion in preserving cervical range of motion, reducing hospital stay and minimizing cost. However, the significance of these differences remains unclear, as laminoplasty clinical outcome scores were generally comparable to laminectomy with fusion. PMID- 27554356 TI - 5-(2-Mercaptoethyl)-1H-tetrazole: Facile Synthesis and Application for the Preparation of Water Soluble Nanocrystals and Their Gels. AB - A facile method for the preparation of the novel capping ligand 5-(2 mercaptoethyl)-1H-tetrazole for the stabilization of water-soluble nanocrystals was developed. This effective synthetic procedure is based on the cycloaddition of sodium azide to 3,3'-dithiobis(propionitrile) followed by the reductive cleavage of a S-S bond with triphenylphosphine. The structure of the synthesized compound was confirmed by single-crystal X-ray analysis. A target tetrazole was successfully applied for the direct aqueous synthesis of CdTe and Au nanocrystals. CdTe nanocrystals capped with 5-(2-mercaptoethyl)-1H-tetrazole were found to reveal high photoluminescence efficiencies (up to 77 %). Nanocrystals capped with this tetrazole ligand are able to build 3D structures in a metal-ion assisted gelation process in aqueous solution. Critical point drying of the as formed hydrogels allowed the preparation of the corresponding aerogels, while preserving the mesoporous structure. PMID- 27554355 TI - Minimally invasive cortical bone trajectory screws placement via pedicle or pedicle rib unit in the lower thoracic spine: a cadaveric and radiographic study. AB - PURPOSE: To evaluate the feasibility of cortical bone trajectory (CBT) screws fixation via pedicle or pedicle rib unit in the cadaveric thoracic spine (T9 T12). METHODS: Computed tomography (CT) images of 100 patients are analyzed by multiplanar reconstruction. Ten cadaveric thoracic spines are used to insert 4.5 * 35.0 mm CBT screws at all levels from T9 to T12. RESULTS: Maximal screw length obtained by CT has a tendency to gradually increase from T9 (29.64 mm) to T12 (32.84 mm), and the difference reaches significant level at all levels except T9 versus T10 (P < 0.01). Maximal screw diameter increases from T9 (4.92 mm) to T12 (7.47 mm) and the difference reaches significant level among all levels (P < 0.01). Lateral angle increases from T9 (7.37 degrees ) to T12 (10.47 degrees ), and the difference reaches significant level among all levels except T11 versus T12. Cephalad angle from T9 to T12 are 19.03 degrees , 22.10 degrees , 25.62 degrees and 27.50 degrees (P < 0.01), respectively. The percentage of the inner and outer pedicle breakage are 2.5 and 22.5 %, respectively. The violation of lateral pedicle wall occurs at T9 and T10, especially for women at T9. CONCLUSIONS: Both radiographic and cadaveric studies establish the feasibility of CBT screws placement via pedicle or pedicle rib unit in the lower thoracic spine (T9-T12). Furthermore, our measurements are also useful for application of this technique. PMID- 27554357 TI - Protein-protein interaction inhibitors: advances in anticancer drug design. AB - INTRODUCTION: Pocket-based drug design has contributed to major scientific breakthroughs in pharmaceutical research and development (R&D). The integrated use of experimental and computational methods, primarily during the early phases of drug discovery, has enabled the development of highly potent and selective small-molecule ligands. In this scenario, the targeting of protein-protein interactions (PPIs) has emerged as an attractive strategy for designing innovative drugs for highly complex diseases, such as cancer. AREAS COVERED: This article focuses on the use of experimental and computational approaches with a diversity of PPI classes and discusses the relevant advances in the field, primarily for oncological applications. Analyses of the target binding pockets and medicinal chemistry approaches used to develop promising PPI inhibitors are provided, with an emphasis on data reported over the past 2 years. EXPERT OPINION: PPI drug discovery is a challenging field that depends completely on accurate structural data. The integration of molecular docking, nuclear magnetic resonance and X-ray crystallography is a cornerstone for the current development of effective PPI inhibitors. Although this field has not reached its peak, several compounds have entered clinical trials over the past few years, providing promising perspectives for novel therapies for highly prevalent and life threatening conditions. PMID- 27554358 TI - Effect of freezing on electrical properties and quality of thawed chicken breast meat. AB - OBJECTIVE: The objective of this research was to study the electrical properties and quality of frozen-thawed chicken breast meat and to investigate the relationship between these parameters at different times of frozen storage. METHODS: Thawed samples of chicken breast muscles were evaluated after being kept in frozen storage at -18 degrees C for different periods of time (1, 2, 3, 4, 5, 6, 7, and 8 months). RESULTS: The results showed that water-holding capacity (WHC) and protein solubility decreased while thiobarbituric acid-reactive substances content increased with increasing storage time. The impedance module of samples decreased during 8-month frozen storage. Pearson correlation coefficients showed that the impedance change ratio (Q value) was significantly (p<0.05) related to pH, color, WHC, lipid oxidation and protein solubility, indicating a good relationship between the electrical properties and qualities of frozen-thawed chicken breast meat. CONCLUSION: Impedance measurement has a potential to assess the quality of frozen chicken meat combining with quality indices. PMID- 27554359 TI - Partial dehulling increases the energy content and nutrient digestibility of barley in growing pigs. AB - OBJECTIVE: The hull attached to the barley kernel can be mechanically removed thus reducing the fiber content of the barley. This experiment was carried out to evaluate the effects of partial dehulling on the nutrient digestibility as well as the digestible energy (DE) and metabolizable energy (ME) content of barley in pigs. METHODS: Two hulled barley samples (high fiber barley [HF] and low fiber barley [LF]) with either high or low fiber contents were obtained from the Hubei and Jiangsu Provinces of China. A portion of the two barleys was mechanically dehulled (dehulled high fiber barley [DHF] and dehulled low fiber barley [DLF]). Thirty barrows (initial BW = 31.5+/-3.2 kg) were assigned to one of five diets in a randomized complete block design. The five diets consisted of 96.9% corn, HF, LF, DHF, or DLF supplemented with 3.1% minerals and vitamins. Each diet was fed to six barrows housed in individual metabolism crates for a 10-d acclimation period followed by a 5-day total but separate collection of feces and urine. RESULTS: The daily loss of gross energy (GE) in feces was lower (p<0.01) for pigs fed DHF than for those fed HF. The daily N intake and fecal N loss were lowest (p<0.01) for pigs fed the corn diet. The DE and ME as well as the apparent total tract digestibility (ATTD) of dry matter, GE, organic matter, neutral detergent fiber (NDF) and acid detergent fiber (ADF) of DHF or DLF were higher (p<0.01) than the values in HF and LF, respectively while the values except the ATTD of NDF and ADF in DLF were higher (p<0.01) than the values in DHF and were comparable to corn. CONCLUSION: The DE and ME contents as well as the ATTD of nutrients in both DHF and DLF barley were improved compared with the HF and LF barley. Moreover, the nutritive value of DLF barley was comparable to the yellow dent corn used in the study. PMID- 27554360 TI - Effects of particle size and adaptation duration on the digestible and metabolizable energy contents and digestibility of various chemical constituents in wheat for finishing pigs determined by the direct or indirect method. AB - OBJECTIVE: This experiment was conducted as a 3*2*2 factorial design to examine the effects of particle size (mean particle size of 331, 640, or 862 MUm), evaluation method (direct vs indirect method) and adaptation duration (7 or 26 days) on the energy content and the apparent total tract digestibility (ATTD) of various chemical components in wheat when fed to finishing pigs. METHODS: Forty two barrows (Duroc*Landrace*Yorkshire) with an initial body weight of 63.0+/-0.8 kg were individually placed in metabolic cages and randomly allotted to 1 of 7 diets with 6 pigs fed each diet. For the indirect method, the pigs were fed either a corn-soybean meal based basal diet or diets in which 38.94% of the basal diet was substituted by wheat of the different particle sizes. In the direct method, the diets contained 97.34% wheat with the different particle sizes. For both the direct and indirect methods, the pigs were adapted to their diets for either 7 or 26 days. RESULTS: A reduction in particle size linearly increased the digestible energy (DE) and metabolizable energy (ME) contents as well as the ATTD of gross energy, crude protein, organic matter, ether extract (EE) and acid detergent fiber (ADF) (p<0.05), and had a trend to increase the ATTD of dry matter of wheat (p = 0.084). The DE, ME contents, and ATTD of gross energy, crude protein, dry matter and organic matter were higher (p<0.05) when determined by the direct method, but the ATTD of ADF, EE, and neutral detergent fiber were higher when determined by the indirect method (p<0.05). Prolongation of the adaption duration decreased the ATTD of neutral detergent fiber (p<0.05) and had a trend to increase the ATTD of EE (p = 0.061). There were no interactions between particle size and the duration of the adaptation duration. The ATTD of EE in wheat was influenced by a trend of interaction between method and adaptation duration (p = 0.074). The ATTD of ADF and EE in wheat was influenced by an interaction between evaluation method and wheat particle size such that there were linear equations (p<0.01) about ATTD of ADF and EE when determined by the direct method but quadratic equations (p = 0.073 and p = 0.088, respectively) about ATTD of ADF and EE when determined by the indirect method. CONCLUSION: Decreasing particle size can improve the DE and ME contents of wheat; both of the direct and indirect methods of evaluation are suitable for evaluating the DE and ME contents of wheat with different particle sizes; and an adaptation duration of 7 d is sufficient to evaluate DE and ME contents of wheat in finishing pigs. PMID- 27554361 TI - Effects of dietary protein level on growth performance and nitrogen excretion of dairy heifers. AB - OBJECTIVE: Protein supplementation is costly and can result in excess nitrogen (N) excretion. The objective of this study was to evaluate the effects of feeding different levels of dietary protein on average daily gain, body size, rumen fermentation, and nitrogen excretion of 8 to 10 month-old Holstein heifers. METHODS: Thirty-six Holstein heifers were divided into 12 blocks according to age (273+/-6.2 d) and were randomly assigned to diets containing a low (10.2% dry matter [DM]), medium (11.9% DM), or high (13.5% DM) level of dietary crude protein (CP). All diets contained approximately 70% roughage and 30% concentrate with similar dietary metabolizable energy (ME) content (2.47 Mcal/kg). RESULTS: Dry matter intake did not differ among the treatments, and average daily gain increased with the increasing dietary protein, 0.79, 0.95, 0.97 kg/d for low, medium, and high group, respectively. Body height increased linearly with increasing dietary CP but no other significant differences in body dimensions were found among the treatments. The increased ratios of dietary CP improved the rate of rear teat length growth remarkably (p<0.05). There was no difference in rumen pH or ruminal major volatile fatty acid (acetate, propionate, and butyrate) concentration among the 3 diets, but rumen ammonia-N concentration increased with the higher dietary CP (p<0.05). Increasing N intake led to increased total N excretion; urinary N excretion was significantly increased (p<0.05) but fecal N excretion was similar among the treatments. CONCLUSION: These data suggest that the diet containing 11.9% CP (ME 2.47 Mcal/kg) could meet the maintenance and growth requirements of 9 to 11 month-old Holstein heifers gaining approximately 0.9 kg/d. PMID- 27554362 TI - Who Are the Men Caring for Maltreated Youth? Male Primary Caregivers in the Child Welfare System. AB - The goal of this study is to better understand the characteristics of men who act as primary caregivers of maltreated children. We examined differences between male primary caregivers (fathers) for youth involved in the child welfare system and female primary caregivers (mothers). We conducted secondary data analyses of the National Survey of Child and Adolescent Well-Being-II baseline data. Overall, primary caregiving fathers and mothers were more similar than different, though a few differences were revealed. Compared to mothers, fathers tended to be older and were more likely to be employed, with a higher household income and older children. Fathers and mothers did not differ in terms of depression or parenting behavior, but there was evidence that mothers have more problems with drug use compared to fathers. Compared to fathers, mothers reported higher levels of internalizing and externalizing problems in their children. Children with male primary caregivers were more likely to have experienced physical abuse but less likely to have experienced emotional abuse or witnessed domestic violence than children with female primary caregivers. These findings may help to inform researchers, practitioners, and policy makers on how to address the needs of male caregivers and their children. PMID- 27554363 TI - [Percutaneous coronary intervention of unprotected left main coronary compared with coronary artery bypass grafting; 3 years of experience in the National Institute of Cardiology, Mexico]. AB - BACKGROUND: The best revascularisation method of the unprotected left main artery is a current and evolving topic. METHODS: A total of 2439 percutaneous coronary interventions (PCI) were registered during a 3-year period. The study included all the patients with PCI of the unprotected left main coronary (n=48) and matched with patients who underwent coronary artery bypass graft (CABG) (n=50). Major adverse cerebral and cardiac events (MACCE) were assessed within the hospital and in outpatients during a 16 month follow up. RESULTS: The cardiovascular risk was greater in the PCI group; logEuroSCORE 16+/-21 vs. 5+/-6, P=.001; clinical Syntax 77+/-74 vs 53+/-39, P=.04. On admission, the PCI group of patients had a higher frequency of ST segment elevation myocardial infarction (STEMI) and cardiogenic shock. The MACCE were similar in both groups (14% vs. 18%, P=.64). STEMI was less frequent in the PCI group (0% vs. 10%, P=.03). Cardiovascular events were lower in the PCI group (2.3% vs. 18%, P=.01), and there was a decrease in general and cardiac mortality (2.3% vs. 12%, P=.08 y 2.3% vs. 8%, P=.24), on excluding the patients with cardiogenic shock as a presentation. MACCE were similar in both groups in the out-patient phase (15% vs. 12%, P=.46). Survival without MACCE, general and cardiac death were comparable between groups (log rank, P=.38, P=.44 and P=.16, respectively). CONCLUSION: Even though the clinical and peri-procedural risk profile of the PCI patients were higher, the in-hospital and out-hospital efficacy and safety were comparable with CABG. PMID- 27554364 TI - Geography of Adolescent Obesity in the U.S., 2007-2011. AB - INTRODUCTION: Obesity remains a significant threat to the current and long-term health of U.S. adolescents. The authors developed county-level estimates of adolescent obesity for the contiguous U.S., and then explored the association between 23 conceptually derived area-based correlates of adolescent obesity and ecologic obesity prevalence. METHODS: Multilevel small area regression methods applied to the 2007 and 2011-2012 National Survey of Children's Health produced county-level obesity prevalence estimates for children aged 10-17 years. Exploratory multivariable Bayesian regression estimated the cross-sectional association between nutrition, activity, and macrosocial characteristics of counties and states, and county-level obesity prevalence. All analyses were conducted in 2015. RESULTS: Adolescent obesity varies geographically with clusters of high prevalence in the Deep South and Southern Appalachian regions. Geographic disparities and clustering in observed data are largely explained by hypothesized area-based variables. In adjusted models, activity environment, but not nutrition environment variables were associated with county-level obesity prevalence. County violent crime was associated with higher obesity, whereas recreational facility density was associated with lower obesity. Measures of the macrosocial and relational domain, including community SES, community health, and social marginalization, were the strongest correlates of county-level obesity. CONCLUSIONS: County-level estimates of adolescent obesity demonstrate notable geographic disparities, which are largely explained by conceptually derived area based contextual measures. This ecologic exploratory study highlights the importance of taking a multidimensional approach to understanding the social and community context in which adolescents make obesity-relevant behavioral choices. PMID- 27554365 TI - Disparities in Diabetes by Education and Race/Ethnicity in the U.S., 1973-2012. AB - INTRODUCTION: Diabetes mellitus incidence has more than doubled in the U.S. over the past 2 decades. Not all sectors of the population have experienced the increase proportionally. The goal of this study was to determine if disparities in diabetes by education and race/ethnicity have increased over time, and if there are differences by gender and birth cohort. METHODS: Repeated cross sectional data were used from the 1973-2012 National Health Interview Survey of adults aged 25-84 years. Logistic regression models were run and predicted probabilities were calculated to determine if disparities in self-reported diabetes by education and race/ethnicity changed over time, by gender and birth cohort (birth before 1946, 1946-1970, 1971 or after). Analyses were conducted in 2014-2015. RESULTS: Relationships between education or race/ethnicity and diabetes were modified by time for people born before 1971, with stronger effect modification for women than men. Inequalities in diabetes prevalence grew over time, although the magnitude of disparities was smaller for the 1946-1970 cohort. For example, in 2005-2012, the gap in diabetes prevalence for women with the highest and lowest levels of education was 12.7% for pre-1946 versus 7.9% for 1946-1970. Similar trends were seen for differences between non-Hispanic whites and non-Hispanic blacks or Hispanics. Results were inconclusive for the youngest cohort. CONCLUSIONS: Diabetes disparities are evident. Smaller differences in later cohorts may indicate that large structural changes in society (e.g., Civil Rights movement, increased educational and economic opportunities) have benefited later generations. PMID- 27554366 TI - Assessment of pain perception following periodontal and implant surgeries. AB - OBJECTIVE: To evaluate patients' pain perception following periodontal or implant surgery and to explore risk factors associated with post-surgical pain. MATERIALS AND METHODS: Patients undergoing periodontal or implant surgery were recruited. Post-surgical pain perception was evaluated by a numeric rating scale (NRS, 1-10) after 1 week. Self-reported durations of pain (DOP) and of swelling (DOS), and consumption of prescriptions were also recorded. Demographic and surgical variables were compared between the groups of mild (MP) and moderate-to-severe post-surgical pain (SP). Factors associated with SP were analysed statistically. RESULTS: Ten surgical types in three categories, comprising 330 surgeries in 253 patients, were included. Overall, 70.3% of the subjects experienced MP, 25.5% experienced moderate pain and 4.2% experienced severe pain. The highest median NRS score was found in subjects having advanced implant surgery [4.0, interquartile range (IQR) 4.00] and the lowest in open flap debridement surgery (1.0, IQR 1.00). The median DOP was 2.0 days (IQR 2.00). Analgesic need (median = 2.0 days, IQR 4.00) was correlated with the DOP (r = 0.406, p < 0.01) and the NRS score (r = 0.358, p < 0.01). Subjects receiving periodontal plastic surgery (OR = 3.20, 95% CI = 1.06-9.71), complex surgery (OR = 2.63, 95% CI = 1.31-5.25), increased surgical extension (OR = 1.78, 95% CI = 1.21-2.62) and increased anaesthesia (OR = 2.32, 95% CI = 1.13-4.76) were more likely to experience SP. CONCLUSIONS: The majority of patients perceived mild post-surgical pain, but the pain level varied among different surgical procedures. Periodontal plastic surgery, complex surgery, surgical extension and anaesthetic volume were associated with more pain. PMID- 27554367 TI - The influence of operator position, height and body orientation on eye lens dose in interventional radiology and cardiology: Monte Carlo simulations versus realistic clinical measurements. AB - OBJECTIVE: This paper aims to provide some practical recommendations to reduce eye lens dose for workers exposed to X-rays in interventional cardiology and radiology and also to propose an eye lens correction factor when lead glasses are used. METHODS: Monte Carlo simulations are used to study the variation of eye lens exposure with operator position, height and body orientation with respect to the patient and the X-ray tube. The paper also looks into the efficiency of wraparound lead glasses using simulations. Computation results are compared with experimental measurements performed in Spanish hospitals using eye lens dosemeters as well as with data from available literature. RESULTS: Simulations showed that left eye exposure is generally higher than the right eye, when the operator stands on the right side of the patient. Operator height can induce a strong dose decrease by up to a factor of 2 for the left eye for 10-cm-taller operators. Body rotation of the operator away from the tube by 45 degrees -60 degrees reduces eye exposure by a factor of 2. The calculation-based correction factor of 0.3 for wraparound type lead glasses was found to agree reasonably well with experimental data. CONCLUSIONS: Simple precautions, such as the positioning of the image screen away from the X-ray source, lead to a significant reduction of the eye lens dose. Measurements and simulations performed in this work also show that a general eye lens correction factor of 0.5 can be used when lead glasses are worn regardless of operator position, height and body orientation. PMID- 27554368 TI - Fetal MRI: incidental findings in the mother. AB - BACKGROUND: Fetal magnetic resonance imaging (MRI) is a routinely used tool in prenatal diagnosis; however, there is a lack of studies evaluating incidental findings observed in the mother. OBJECTIVE: This study describes and quantifies incidental findings observed in the mother during fetal MRI. MATERIALS AND METHODS: We reviewed all fetal MRI studies at the University of Minnesota Medical Center from February 2008 to September 2014. Two pediatric radiologists retrospectively conducted a consensus evaluation. The maternal findings were categorized into neurologic, gynecologic, urinary, gastrointestinal and musculoskeletal. Hydronephrosis consistent with the stage of pregnancy was recorded but was not included as an abnormal finding. Abnormal findings were classified into three groups, depending on their clinical significance: level I (low), level II (medium) and level III (high). RESULTS: We evaluated 332 pregnant patients with a mean age of 29.3 years and a mean gestational age of 29 weeks. Of these, 55.4% had at least 1 incidental finding, for a total of 262 incidental maternal findings. Of the 262 abnormalities, 113 (43.1%) were neurologic, 69 were gynecologic (26.3%), 36 (13.7%) urinary, 24 (9.2%) gastrointestinal and 20 (7.6%) musculoskeletal. Of the 262 incidental findings, 237 (90.5%) were level I, 24 (9.2%) were level II and 1 (0.4%) was level III. CONCLUSION: Our results suggest that although the vast majority of incidental maternal findings are benign, more significant findings are still encountered and should be expected. PMID- 27554369 TI - A zebrafish mosaic assay to study mammalian stem cells in real time in vivo. AB - The differentiation potentials of stem cells have been evaluated by various in vivo and in vitro assays. However, these assays have different limitations hindering efficient study of mammalian stem cells. Here we describe a rapid and powerful mosaic assay to study the differentiation potentials of stem cells in real time in vivo by using zebrafish embryo. We transplanted mouse neural stem cells into zebrafish embryos at different developmental stages and found that they mainly formed neural tissues while occasionally trans-differentiated into mesoderm- and endoderm-derived tissues. Because zebrafish embryo is transparent, the behaviors of transplanted mouse stem cells can be easily tracked in a real time manner and at single-cell resolution. We expect that this assay may be widely applied to explore the in vivo behaviors of any stem cells available. PMID- 27554371 TI - Association between Urine Creatinine Excretion and Arterial Stiffness in Chronic Kidney Disease: Data from the KNOW-CKD Study. AB - BACKGROUND/AIMS: Previous studies have shown that low muscle mass is associated with arterial stiffness, as measured by pulse wave velocity (PWV), in a population without chronic kidney disease (CKD). This link between low muscle mass and arterial stiffness may explain why patients with CKD have poor cardiovascular outcomes. However, the association between muscle mass and arterial stiffness in CKD patients is not well known. METHODS: Between 2011 and 2013, 1,529 CKD patients were enrolled in the prospective Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). We analyzed 888 participants from this cohort who underwent measurements of 24-hr urinary creatinine excretion (UCr) and brachial-ankle PWV (baPWV) at baseline examination. The mean of the right and left baPWV (mPWV) was used as a marker of arterial stiffness. RESULTS: The baPWV values varied according to the UCr quartile (1,630+/-412, 1,544+/-387, 1,527+/-282 and 1,406+/-246 for the 1st to 4th quartiles of UCr, respectively, P<0.001). For each 100 mg/d increase in UCr, baPWV decreased by 6m/sec in a multivariable linear regression model fully adjusted for traditional and renal cardiovascular risk factors. The odds ratio of the 1st quartile for high baPWV (highest quintile of mPWV) compared with the 4th quartile was 2.62 (1.24-5.54, P=0.011) in a logistic model fully adjusted for traditional and renal cardiovascular risk factors. CONCLUSION: Low muscle mass estimated by low UCr was associated high baPWV in pre-dialysis CKD patients in Korea. Further studies are needed to confirm the causal relationship between UCR and baPWV, and the role of muscle mass in the development of cardiovascular disease in CKD. PMID- 27554370 TI - Pharmacological Treatment of Post-Prostatectomy Incontinence: What is the Evidence? AB - Urinary incontinence is a common and debilitating problem, and post-prostatectomy incontinence (PPI) is becoming an increasing problem, with a higher risk among elderly men. Current treatment options for PPI include pelvic floor muscle exercises and surgery. Conservative treatment has disputable effects, and surgical treatment is expensive, is not always effective, and may have complications. This article describes the prevalence and causes of PPI and the current treatment methods. We conducted a search of the PUBMED database and reviewed the current literature on novel medical treatments of PPI, with special focus on the aging man. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and alpha-adrenergic drugs have been proposed as medical treatments for PPI. Most studies were small and used different criteria for quantifying incontinence and assessing treatment results. Thus, there is not enough evidence to recommend the use of these medications as standard treatment of PPI. To determine whether medical therapy is a viable option in the treatment of PPI, randomized, placebo-controlled studies are needed that also assess side effects in the elderly population. PMID- 27554373 TI - Influence of Massive and Long Distance Migration on Parasite Epidemiology: Lessons from the Great Wildebeest Migration. AB - Very little is known about the influence of massive and long distance migration on parasite epidemiology. Migration can simultaneously minimize exposure to common parasites in their habitats and increase exposure to novel pathogens from new environments and habitats encountered during migration, while physiological stress during long distance movement can lead to immune suppression, which makes migrants vulnerable to parasites. In this paper, we investigated the diversity, prevalence, parasite load, co-infection patterns and predilection sites of adult gastrointestinal helminths in 130 migrating wildebeests and tested for their relation with animal age, sex and migration time (which also could indicate different migration routes), and compared them with the non-migratory wildebeest. Surprisingly, only four parasite species were found, Oesophagostomum columbianum, Haemonchus placei, Calicophoron raja and Moniezia expansa, which were lower than in non-migratory wildebeest reported in the literature. These parasites were generalists, infecting livestock, and suggests that wildebeest and livestock, because of their interaction during migration, have a cross-infection risk. There was a negative relation between parasites diversity, prevalence and intensity of infection, and host age, which suggests that wildebeests acquire protective immunity against these parasites as they get older. Prevalence and intensity of infection were higher among wildebeest crossing the Mara Bridge (early migrants) compared to those crossing the Serena (late migrants), which suggests that early migrants (or migrants originating from different areas) have varying infection intensities. The prevalence and intensity of infection were higher in males compared to females and may be due to ecological, behavioural, or physiological differences between males and females. Our findings compared to those of previous studies suggest that migration may provide a mechanism to minimize exposure of hosts to common parasites through migratory escape, but this result awaits examination of helminths epidemiology of non-migratory wildebeests from areas of migrant origins. The potential parasitic cross-infection between wildebeests and livestock is a real risk to be taken into account in the management of wildebeest migration corridors. PMID- 27554374 TI - Generation of alpha-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes. AB - Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the alpha-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT (DAF/CD39/TFPI/C1-INH/TNFAIP3)/+] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product. All five individual protein products were successfully produced as determined by western blotting of umbilical cords from the newborn transgenic pigs. Although gross observation and histological examination revealed no significant pathological abnormality in transgenic piglets, hematological examination found that the transgenic piglets had abnormally low numbers of platelets and WBCs, including neutrophils, eosinophils, basophils, and lymphocytes. However, transgenic piglets had similar numbers of RBC and values of parameters related to RBC compared to the control littermate piglets. These data suggest that transgenic expression of those human genes in pigs impaired hematopoiesis except for erythropoiesis. In conclusion, our data suggest that transgenic expression of up to five different genes can be efficiently achieved and provide the basis for determining optimal dosages of transgene expression and combinations of the transgenes to warrant production of transgenic donor pigs without health issues. PMID- 27554375 TI - Cytokines in saliva increase in head and neck cancer patients after treatment. AB - OBJECTIVE: Approximately one-third of advanced head and neck squamous cell carcinomas (HNSCCs) recur within 2 years of treatment. Due to ease of collection, saliva is of interest to monitor changes that correlate with treatment. Previously this was a challenge due to xerostomia after conventional radiation. The emergence of gland-sparing radiation has made it possible to collect saliva post-treatment. This study investigated changes in cytokines in saliva pre- and post-treatment to provide foundational knowledge for future studies exploring the use of saliva to monitor treatment response. STUDY DESIGN: Pre- and post treatment saliva was evaluated for 8 cytokines by multiplex assay and enzyme linked immunosorbent assay. RESULTS: In oropharyngeal HNSCC, secretion of epidermal growth factor (EGF), GROalpha (Growth-regulated protein alpha), interleukin (IL)-1alpha, IL-beta, IL-6, IL-8, tumor necrosis factor-alpha, and vascular endothelial growth factor increased significantly post-treatment. In additional patients, significant increases of GR-alpha and IL-6 were validated, but EGF showed no change. CONCLUSIONS: The uniqueness of this study is its comparison of salivary cytokines from HNSCC patients pre- and post-treatment. PMID- 27554376 TI - Keratocystic odontogenic tumor overexpresses invadopodia-related proteins, suggesting invadopodia formation. AB - OBJECTIVE: Keratocystic odontogenic tumor (KOT) is an odontogenic neoplasm that shows aggressive clinical behavior and local invasiveness. Invadopodia are actin rich cellular protrusions exhibiting proteolytic pericellular activity, thereby inducing focal invasion in neoplastic cells and increasing neoplasms aggressiveness. Thus, this study aimed to evaluate immunoexpression of invadopodia-related proteins, cortactin, MT1-MMP, Tks4, and Tks5, in KOT. STUDY DESIGN: Immunohistochemistry of 16 cases of KOT, eight cases of calcifying cystic odontogenic tumor (CCOT), and eight samples of the oral mucosa (OM) was carried out to assess the expression of the above described invadopodia-related proteins in the basal and suprabasal layer. RESULTS: KOT samples showed higher and significant immunoexpression of cortactin, MT1-MMP, TKs4, and TKs5 compared with the CCOT and OM samples. Significant expression of all these proteins was observed in the basal layer compared with the suprabasal layer in KOT. CONCLUSIONS: Overexpression of cortactin, MT1-MMP, TKs4, and TKs5 was observed in KOT compared with samples of CCOT and OM. These proteins were also overexpressed in the basal over the suprabasal layer of KOT samples. Taken together, these results suggest the participation of invadopodia-related proteins on the pathogenesis of this lesion. PMID- 27554377 TI - Delayed tooth emergence in children infected with human immunodeficiency virus. AB - OBJECTIVE: There is limited evidence that early deficits in growth might be reflected in tooth emergence in children infected with human immunodeficiency virus (HIV). The purpose of this study was to prospectively evaluate tooth emergence timing between children positive and negative for HIV in the exposed and unexposed groups, respectively. STUDY DESIGN: A longitudinal study of children positive for HIV and HIV-negative household peers, aged 2 to 15 years was conducted between 1993 and 1996. Emergence status was determined for the maxillary and the mandibular permanent first molars and the central and lateral incisors. A multivariable, discrete time, proportional hazards model was fitted to the data. Median age of emergence for each of the six pairs of teeth was calculated using the parameter estimates from the regression model. RESULTS: A total of 116 participants (62 HIV positive, 54 HIV negative) completed six examinations over the 36-month study period. Statistical differences in tooth emergence timing were observed for five of the six tooth pairs, with children positive for HIV being less likely to have emergence of the corresponding tooth compared with the children negative for HIV. Age differences for each tooth pair ranged from 0.7 to 1.5 years, with a median emergence age difference of 1.03 years. CONCLUSIONS: Delayed tooth emergence of the permanent dentition was observed in children with HIV. PMID- 27554378 TI - Management of dental extraction in patients undergoing anticoagulant oral direct treatment: a pilot study. AB - OBJECTIVE: The main goal of this study was to compare the incidence of postoperative bleeding events after dental extractions between patients treated with direct oral anticoagulants (DOACs) and those treated with vitamin K antagonists (VKAs) without withdrawal of oral anticoagulant therapy (OAT). Our second objective was to evaluate the risk factors affecting postoperative hemorrhage after tooth extraction in patients taking DOACs. STUDY DESIGN: This prospective observational study included 51 patients who were being treated with oral anticoagulants and required dental extractions. They were divided into two groups: 31 patients receiving a DOAC and 20 control patients taking VKA with an international normalized ratio between 2.0 and 3.0. In both groups, extractions were performed under continued OAT, and the same local hemostatic measures were applied. All procedures were performed in an outpatient facility. A bleeding event was defined as persistent oozing or marked hemorrhage over 20 minutes after tooth extraction despite local hemostasis procedures or all bleeding episode occurring during the first postoperative week. RESULTS: Five patients taking DOACs had seven bleeding episodes, and four patients receiving VKAs had five bleeding episodes during the postoperative follow-up period. The difference in the number of bleeding events between the two groups was not statistically significant (adjusted odds ratio = 0.77; 95% confidence interval 0.19-3.19; P = .723). Eleven (91.67%) bleeding events were mild and controlled by mechanical compression with gauzes, and one (8.33 %) was managed with a revision of the wound, application of fibrin glue, and resuturing. No bleeding required hospitalization or blood transfusion. All bleeding episodes occurred during the first 3 postoperative days. CONCLUSIONS: According to our preliminary outcome data, dental extractions can be performed safely in an outpatient facility in patients treated with DOAC by applying local hemostatic measures, without interrupting or modifying OAT. PMID- 27554379 TI - Management of coronal discolouration following a regenerative endodontic procedure in a maxillary incisor. AB - Pulpal necrosis and infection in an immature anterior tooth subsequent to traumatic injury is a challenging situation. Regenerative endodontics, resulting in continued development of the tooth, provides a biological response to this clinical challenge. Regenerative endodontic procedures require disinfection of the infected root canal and sealing of the pulp canal space. Mineral trioxide aggregate (MTA) provides a good seal, is biocompatible and allows the formation of a hard tissue to occur within the root canal. MTA, however, can lead to significant staining of the crown of the tooth that is difficult to mask. This case report describes the management of discolouration in an 11 year old girl subsequent to a regenerative endodontic procedure in an immature traumatized maxillary central incisor. PMID- 27554380 TI - New steps of elastography for the diagnosis of chronic pancreatitis. AB - Editorial on the role of ultrasound guided elastography for the diagnosis of chronic pancreatitis. PMID- 27554381 TI - Fibrolamellar hepatocellular carcinoma: a rare entity diagnosed by abdominal ultrasound. AB - We present the case of a young man with a hepatic mass in which ultrasound gives great and immediate support for diferential diagnosis. PMID- 27554382 TI - Common bile duct perforation sealed with a metal fully-covered stent. AB - A common bile duct perforation due to sphincteroplasty is reported. It was managed by temporary insertion of a metal fully covered stent with good outcomes. Images from the procedure are provided. PMID- 27554383 TI - Gastric inflammatory fibroid polyp mimicking a gastrointestinal stromal tumour. AB - Inflammatory fibroid polyp of the gastrointestinal tract is a rare, benign neoplasm, most frequently located in the gastric antrum. Symptoms depend on the location and the size of the lesion. Biopsies are limited for the diagnosis of inflammatory fibroid polyps and diagnosis may not be possible until resection. The authors present a case of a 55-year-old woman, presenting with an upper gastrointestinal bleeding due to a large gastric inflammatory fibroid polyp imitating a gastrointestinal stromal tumor. PMID- 27554384 TI - Gastric necrosis secondary to strangulated giant paraesophic hiatal hernia. AB - Asymptomatic giant hiatal hernia comprises a relatively common disease, mostly presented in women with 50 years onwards. The therapeutic approach remains controversial in recent years. Under the latest SAGES'revision, all the symptomatic hernias must be repaired, but the symptomatic hiatal hernia definition isn't even now established. We present the case os a A 67 - year old woman with an asymptomatic hiatal hernia, that is admitted to our hospital owing to toracic and abdominal pain. This pain was related with food intake for 6 months. The patient presents a clear worsening in the last 24 hours, with no other asociated symptomatology. Suspecting an incarcerated hiatal hernia with stomach perforation, the patient is taken to theatre for a laparotomy during the early hours. An atypic gastrectomy of the greater curvature with a gastropexy is performed with fixation to the anterior abdominal wall. The surgery is completed with a feeding jejunostomy. The Manegement of giant paraesophagic hernias, still remains as one of the challenge of the esophageal surgeons. PMID- 27554385 TI - Hemangioma of the rectum - How misleading can hematochezia be? AB - We present the case of an 18-year-old male patient that was referred to our gastrenterology department with history of intermittent painless hematochezia since childhood. During such instances, he was diagnosed with bowel intussusception, eosinophilic gastroenteritis and inflammatory bowel disease at 4, 6 and 8 years old, respectively. He underwent treatment with 5-aminosalicylic acid for two years, without improvement of symptoms. He was then lost to follow up until our observation. His physical examination was unremarkable except for digital rectal examination which found a nodular compressible mass by the palpating finger. Blood tests revealed a mild iron deficiency anemia. The colonoscopy showed an extended reddish and bluish multinodular submucosal mass in the rectum, suggesting diffuse cavernous hemangioma of the rectum (DHCR). The Magnetic Resonance Imaging, showed diffuse thickening of the entire rectum extending into the distal sigmoid with the mesorectum revealing multiple serpiginous structures, corresponding to abnormal blood vessels. After discussion, we considered to perform a sphincter-sparing procedure, namely pull through transection and coloanal anastomosis. However, intervention was ruled out by the patient because of his fear of anal incontinence and permanent colostomy. We adopted a conservative strategy with clinical surveillance and iron supplementation. At the present, the patient remains with intermittent rectal bleeding, referring poor quality of life due to his ongoing symptoms. This is a rare case of DHCR. Despite of being a benign disease, the management of DHCR requires a sphincter mucosectomy and pull-through coloanal sleeve anastomosis which has become the first-line procedure. The surgical outcomes are non expectable in 32% with permanent sphincter lesion or with incomplete DHCR removal. As in this case, the surgeons or patients refusal to perform the intervention is common which represents a challenge to the clinical follow-up. PMID- 27554386 TI - Spontaneous intramural hematoma of the colon. AB - A 73-year-old man was admitted to our clinic with sudden left quadrant abdominal pain and hematochezia. There was no history of trauma. He denied other symptoms or taking off-the-counter medication. His medical history was relevant for ischemic and aortic-mitral valve disease with prosthetic valves for which he was medicated with aspirin and warfarin. On physical examination the patient presented normal vital signs with tenderness on palpation of the left side of the abdomen. Laboratory tests revealed moderate anemia (10.8 g/dl) and thrombocytopenia (135.000x10^9 U/L) with therapeutic international normalized ratio (2.53). Colonoscopy revealed an extensive area of erythematous and bluish mucosa with an apparent torsion of the proximal descending colon around a volumous hematoma measuring 6.5x3 cm (Figure 1 A-C). Urgent abdominal CT confirmed the presence of a large intramural hematoma of the descending colon (Figure 2 A-B). A conservative approach was adopted with temporary suspension of anticoagulation. Given the high thrombotic risk, abdominal ultrasound was performed after 72 hours showing considerable reduction in the size of the hematoma. Anti-coagulation was then resumed without complications. One month later, colonoscopy was repeated showing complete healing of the mucosa. The increasing use of anti-aggregating and anti-coagulant therapy, especially in elderly patients, explains the increasing incidence of bleeding events seen in this population. However, gastrointestinal hematomas are estimated to occur in only 1 for every 250.000 anti-coagulated patients. Diagnosis is based on characteristic radiologic findings. While most parietal hematomas can be approached conservatively, surgery is indicated in the presence of complications or persistence of the hematoma. PMID- 27554387 TI - Population Genetic Structure and Marker Trait Associations Using Morphological, Phytochemical and Molecular Parameters in Habenaria edgeworthii-a Threatened Medicinal Orchid of West Himalaya, India. AB - Habenaria edgeworthii Hook. f. ex Collett is an important terrestrial orchid used in different Ayurvedic formulations. In the present study, variations among morphological, phytochemical and molecular markers were assessed. A significant difference was observed among populations using morphological traits. Inter simple sequence repeat (ISSR) data revealed lower genetic diversity at population level (He = 0.207) as compared to species level (He = 0.334). Analysis of molecular variance (AMOVA) indicates 74 % variation among populations and 26 % within population. Tuber extracts showed significantly (p < 0.05) higher total phenolics and flavonoids among the populations. Antioxidant activity determined by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) assays exhibited considerable antioxidant potential. Furthermore, the associations between molecular and morphological and phytochemical attributes were studied using multiple regression analysis (MRA). Several ISSR fragments were associated with some morphological and phytochemical traits. These ISSR fragments can be useful for breeding programme of the species when no other genetic information, such as linkage maps and quantitative trait loci, is available. PMID- 27554389 TI - A narrative review: The effects of opioids on sleep disordered breathing in chronic pain patients and methadone maintained patients. AB - BACKGROUND AND OBJECTIVES: Opioids increase the risk for sleep disordered breathing (SDB), but there are few studies examining the prevalence and risk factors for SDB, specifically central sleep apnea (CSA), and obstructive sleep apnea (OSA) in chronic pain patients on opioids as well as methadone maintained patients (MMPs). METHODS: A literature review was conducted in which SDB was confirmed by polysomnography (PSG) in chronic pain patients on opioids as well as patients with a diagnosis of an opioid use disorder or opioid dependence on methadone maintenance treatment (MMT). RESULTS: About 22 reports were included. Six were with MMPs, and 16 were with chronic pain patients on opioids. Among MMPs, the prevalence of SDB ranged from 42.3% to 70%; 0-60% had CSA and 10-35.2% had OSA. In chronic pain patients on opioids, the prevalence of SDB ranged from 71% to 100%; 17-80% had CSA and 20-39% had OSA. In MMPs, studies found a positive association between BMI, weight gain, duration of MMT, non-Caucasian race and the number of obstructive apneas, as well as blood methadone concentrations and the number of central apneas. In chronic pain patients on opioids, older age, higher BMI, male gender, and higher opioid doses predicted more obstructive apneas; older age, lower BMI, male gender, higher pain levels, higher benzodiazepine doses, and higher opioid doses predicted more central apneas. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: CSA and OSA are common in MMPs and chronic pain patients on opioids. Among chronic pain patients, higher opioid doses appear to be a risk factor for CSA, and to a lesser extent OSA. Therefore, it is important for providers to screen these patient populations for SDB. (Am J Addict 2016;25:452 465). PMID- 27554388 TI - Variable disruption of a syntactic processing network in primary progressive aphasia. AB - Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network. PMID- 27554390 TI - Detection and clinical significance of glomerular M-type phospholipase A2 receptor in patients with idiopathic membranous nephropathy. AB - BACKGROUND: Glomerular M-type phospholipase A2 receptor (PLA2 R) is important for diagnosing idiopathic membranous nephropathy (IMN). The relation between glomerular PLA2 R expression and response to treatment remains to be explored. AIMS: We conducted the study to explore the positive rate and clinical significance of glomerular M-type PLA2 R in IMN patients. METHODS: A total of 122 IMN patients receiving neither glucocorticoid nor immunosuppressant therapy prior to renal biopsies was included and followed for more than 1 year. The control group comprised 30 patients with secondary membranous nephropathy and 100 patients with non-membranous forms of nephropathy. PLA2 R level and IgG subclasses in glomeruli were detected. The primary end-point was the reduction of proteinuria to less than 50% of baseline value. RESULTS: A total of 82.0% of patients with IMN had positive glomerular PLA2 R deposits, compared with 16.7% in the secondary membranous nephropathy group (P < 0.001). Additionally, PLA2 R positive expression combined with IgG4 >= 2+ was found in 94.3% IMN patients, compared with 40.0% in secondary membranous nephropathy patients (P < 0.01). Among IMN patients, the remission rate of proteinuria after either glucocorticoid or glucocorticoid combined immunosuppressant therapy for at least 6 months was 83.9% in the PLA2 R-positive group compared with 54.5% in the negative group (P < 0.05). CONCLUSION: The positive rate of glomerular PLA2 R was more prevalent in IMN patients. Both PLA2 R and IgG4 glomerular deposits may help in discriminating between idiopathic and secondary membranous nephropathy. IMN patients with positive PLA2 R expression probably have a more beneficial response to glucocorticoid and/or immunosuppressant therapy. PMID- 27554392 TI - In Vivo Measurement in Pigs of Wash-In Kinetics of Xenon at its Site of Action. AB - BACKGROUND: Xenon (Xe) in many respects is an ideal anaesthetic agent. Its blood/gas partition coefficient is lower than that of any other anaesthetic, enabling rapid induction of and emergence from anaesthesia. While the whole body kinetics during wash-in of inhalational anaesthesia is well known, data describing the pharmacokinetics of xenon in the cerebral compartment at the site of action are still largely missing. METHODS: In order to illuminate xenon's cerebral pharmacokinetics, we anaesthetised five pigs and measured arterial, mixed- and sagittal sinus-venous blood, as well as end-expiratory gas concentrations of xenon by gas chromatography-mass spectrometry (GCMS) up to 30 minutes after starting the anaesthetic gas mixture. RESULTS: Despite xenon's fast onset of effect the half-time for equilibration between xenon concentration in arterial blood and at the site of action is measured to be 1.49 +/- 0.04 minutes versus 3.91 +/- 0.1 minutes. Successful loading of xenon in the brain during inhalational anesthesia was accomplished after approximately 15 minutes although the end-expiratory xenon concentration reached a plateau after 7 minutes. Thus cerebral xenon uptake rate is only moderate, xenon fast onset of action being largely due to its extremely fast alveolar uptake. CONCLUSIONS: To ensure safety and precise control during anaesthesia we need a profound knowledge about to what extent the measured end-tidal concentrations reflect the drug concentrations in the target tissue. The results of this study expand our knowledge about the temporal characteristics of xenon's pharmacokinetics at its site of action and provide the basis for appropriate clinical protocols and experimental designs of future studies. PMID- 27554391 TI - Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system. AB - Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCalpha. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERalpha, ERbeta, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID- 27554393 TI - Ontogenetic onset of immune-relevant genes in the common sole (Solea solea). AB - Fish are free-living organisms since initial stages of development and are exposed to numerous pathogens before their lymphoid organs have matured and adaptive immunity has developed. Susceptibility to diseases and juvenile mortality represent key critical factors for aquaculture. In this context, the characterization of the appearance kinetics of the immune system key members will be useful in understanding the ability of a particular species in generating immune protection against invading pathogens at different developmental stages. The present study characterized, for the first time, the transcriptional onset of un-explored relevant genes of both innate and adaptive immune system during the Solea solea ontogenesis. Gene expression profiles of immune relevant genes was investigated, by means of DNA microarray, in ten developmental stages, from hatching (1 day post-hatching, dph) to accomplishment of the juvenile form (33 dph). The obtained results revealed that transcripts encoding relevant members of innate immune repertoire, such as lysozyme, AMPs (hepcidin, beta-defensin), PPRs and complement components are generally characterized by high expression levels at first stages (i.e. hatch and first feeding) indicating protection from environmental pathogens even at early development. Transcription of adaptive immune genes (i.e. Class I and class II MHC, TCRs) differs from that of the innate immune system. Their onset coincides with metamorphosis and larvae-to juvenile transition, and likely overlaps with the appearance and maturation of the main lymphoid organs. Finally, data collected suggest that at the end of metamorphosis S. solea cell-mediated immune system hasn't still undergone full maturation. PMID- 27554394 TI - Toxic dinoflagellates and Vibrio spp. act independently in bivalve larvae. AB - Harmful algal blooms (HABs) and marine pathogens - like Vibrio spp. - are increasingly common due to climate change. These stressors affect the growth, viability and development of bivalve larvae. Little is known, however, about the potential for interactions between these two concurrent stressors. While some mixed exposures have been performed with adult bivalves, no such work has been done with larvae which are generally more sensitive. This study examines whether dinoflagellates and bacteria may interactively affect the viability and immunological resilience of blue mussel Mytilus edulis larvae. Embryos were exposed to environmentally relevant concentrations (100, 500, 2500 & 12,500 cells ml(-1)) of a dinoflagellate (Alexandrium minutum, Alexandrium ostenfeldii, Karenia mikimotoi, Protoceratium reticulatum, Prorocentrum cordatum, P. lima or P. micans), a known pathogen (Vibrio coralliilyticus/neptunius-like isolate or Vibrio splendidus; 10(5) CFU ml(-1)), or both. After five days of exposure, significant (p < 0.05) adverse effects on larval viability and larval development were found for all dinoflagellates (except P. cordatum) and V. splendidus. Yet, despite the individual effect of each stressor, no significant interactions were found between the pathogens and harmful algae. The larval viability and the phenoloxidase innate immune system responded independently to each stressor. This independence may be related to a differential timing of the effects of HABs and pathogens. PMID- 27554395 TI - Two isoforms of piscidin from Malabar grouper, Epinephelus malabaricus: Expression and functional characterization. AB - Two isoforms of piscidin from Malabar grouper (Epinephelus malabaricus), EmPis-1 and EmPis-2, were cloned and studied. EmPis-1 and EmPis-2 showed the different in the 3'UTR features of mRNA and gene expression patterns. AUUUA-motif-containing ARE was found in mRNA of EmPis-1, but not in that of EmPis-2. EmPis-1 and EmPis-2 expressed not only in the potential sites of pathogen entry, but also in grouper's immune-related tissues such as head kidney (HD), peripheral blood leukocytes (PBL) and spleen. The expression level of EmPis-1 was higher than that of EmPis-2 in most fish tissues. Expression of both EmPis-1 and EmPis-2 were upregulated by V. parahaemolyticus significantly in the PBL, HD and spleen. Besides, expression of EmPis-1 was upregulated in gills. The putative mature peptides of EmPis-1 and EmPis-2, which were predicted to adopt an amphipathic alpha-helical conformation, posessed excellent microbicidal activities against both gram-negative and -positive bacteria. The hemolytic activity of the putative mature peptides of EmPis-1 and EmPis-2 increased in a dose-dependent manner to both grouper erythrocytes and rabbit erythrocytes. Interestingly, grouper erythrocytes were less vulnerable than rabbit erythrocytes to the peptides. Grouper piscidins excluded the signal peptide were not the inactive precursors but possessed high microbicidal activity evidenced by minimum bactericidal concentration (MBC) assay and by the scanning electron microscope (SEM) observation. The present phylogenetic analysis did not support the suggestion that piscidins are ancient AMPs widespread across invertebrate and vertebrate taxa, and that piscidins are included in the cecropin superfamily. Collectively, the present data improve our understanding of the piscidin family, and give greater insights into EmPis-1 and EmPis-2 of the grouper immune system. PMID- 27554396 TI - Promoting Authentic Learning for Our Students. PMID- 27554397 TI - Open Mouth, Open Mind: Expanding the Role of Primary Care Nurse Practitioners. AB - Oral health is essential to overall health at any age, although in children it is particularly important because poor oral health can have a deleterious effect on deciduous and permanent dentition. For decades, oral health providers have urged primary care providers to incorporate oral health assessment, risk factor identification, parent education, and preventive therapy into routine well-child visits. Despite recommendations from various professional associations and governmental organizations, the incidence of dental disease in young children remains relatively unchanged. Although the literature has clearly demonstrated that preventive care treatments, such as the application of fluoride varnish performed in the primary care setting, improve oral health in children, very few primary care providers include oral health services in their well-child visits. The purpose of this article is to reduce the barriers and knowledge gaps identified in recent pediatric oral health research and educate primary care nurse practitioners on the application of fluoride varnish to reduce the risk of the development of dental caries in young children. PMID- 27554398 TI - Anisotropic etching of platinum electrodes at the onset of cathodic corrosion. AB - Cathodic corrosion is a process that etches metal electrodes under cathodic polarization. This process is presumed to occur through anionic metallic reaction intermediates, but the exact nature of these intermediates and the onset potential of their formation is unknown. Here we determine the onset potential of cathodic corrosion on platinum electrodes. Electrodes are characterized electrochemically before and after cathodic polarization in 10 M sodium hydroxide, revealing that changes in the electrode surface start at an electrode potential of -1.3 V versus the normal hydrogen electrode. The value of this onset potential rules out previous hypotheses regarding the nature of cathodic corrosion. Scanning electron microscopy shows the formation of well-defined etch pits with a specific orientation, which match the voltammetric data and indicate a remarkable anisotropy in the cathodic etching process, favouring the creation of (100) sites. Such anisotropy is hypothesized to be due to surface charge induced adsorption of electrolyte cations. PMID- 27554399 TI - Optical conductivity of a 2DEG with anisotropic Rashba interaction at the interface of LaAlO3/SrTiO3. AB - We study optical conductivity of a two-dimensional electron gas with anisotropic k-cubic Rashba spin-orbit interaction formed at the LaAlO3/SrTiO3 interface. The anisotropic spin splitting energy gives rise to different features of the optical conductivity in comparison to the isotropic k-cubic Rashba spin-orbit interaction. For large carrier density and strong spin-orbit couplings, the density dependence of Drude weight deviates from the linear behavior. The charge and optical conductivities remain isotropic despite anisotropic nature of the Fermi contours. An infinitesimally small photon energy would suffice to initiate inter-band optical transitions due to degeneracy along certain directions in momentum space. The optical conductivity shows a single peak at a given photon energy depending on the system parameters and then falls off to zero at higher photon energy. These features are lacking for systems with isotropic k-cubic Rashba spin-orbit coupling. These striking features can be used to extract the information about nature of the spin-orbit interaction experimentally and illuminate some light on the orbital origin of the two-dimensional electron gas. PMID- 27554400 TI - The benefits of cooling boar semen in long-term extenders prior to cryopreservation on sperm quality characteristics. AB - This study investigated the effects of long-term extenders on post-thaw sperm quality characteristics following different holding times (HT) of boar semen at 17 and 10 degrees C. Sperm-rich fractions, collected from five boars, were diluted in Androhep((r)) Plus (AHP), Androstar((r)) Plus (ASP), Safecell((r)) Plus and TRIXcell((r)) Plus (TCP) extenders. The extended semen samples were held for 2 hr at 17 degrees C (HT 1) and additionally for 24 hr at 10 degrees C (HT 2), after they were evaluated and frozen. CASA sperm motility and motion patterns, mitochondrial membrane potential (MMP), plasma membrane integrity (PMI) and normal apical ridge (NAR) acrosome integrity were assessed in the pre-freeze and frozen-thawed semen. The Vybrant Apoptosis Assay Kit was used to analyse the proportions of viable and plasma membrane apoptotic-like changes in spermatozoa. Results indicated that boar variability, extender and HT significantly affected the sperm quality characteristics, particularly after freezing-thawing. Differences in the pre-freeze semen were more marked in the sperm motion patterns between the HTs. Pre-freeze semen in HT 2 showed significantly higher VCL and VAP, whereas no marked effects were observed in the sperm membrane integrity and viability (YO-PRO-1(-) /PI(-) ) among the extenders. Post-thaw sperm TMOT and PMOT were significantly higher in the AHP and ASP extenders of HT 2 group, whereas VSL, VCL and VAP were markedly lower in the TCP extender. Furthermore, spermatozoa from the AHP- and ASP-extended semen of HT 2 group were characterized by higher MMP, PMI and NAR acrosome integrity following freezing-thawing. In most of the extenders, the incidence of frozen-thawed spermatozoa with apoptotic-like changes was greater in HT 1. The findings of this study indicate that holding of boar semen at 10 degrees C for 24 hr in long-term preservation extenders modulates post-thaw sperm quality characteristics in an extender-dependent manner. These results will further contribute to the improvement in the cryopreservation technology of boar semen. PMID- 27554401 TI - Problematizing in nursing education: Freire's contribution to transformative practice. PMID- 27554402 TI - Deaths from heart disease in UK fall, but prevalence is unchanged. PMID- 27554403 TI - A chemist's legacy. PMID- 27554404 TI - Organometallic chemistry: Fused ferrocenes come full circle. PMID- 27554405 TI - Density functional theory: Fixing Jacob's ladder. PMID- 27554406 TI - C-H fluorination: U can fluorinate unactivated bonds. PMID- 27554407 TI - Enzyme design: Functional Frankensteins. PMID- 27554408 TI - Oligomeric ferrocene rings. AB - Cyclic oligomers comprising strongly interacting redox-active monomer units represent an unknown, yet highly desirable class of nanoscale materials. Here we describe the synthesis and properties of the first family of molecules belonging to this compound category-differently sized rings comprising only 1,1' disubstituted ferrocene units (cyclo[n], n = 5-7, 9). Due to the close proximity and connectivity of centres (covalent Cp-Cp linkages; Cp = cyclopentadienyl) solution voltammograms exhibit well-resolved, separated 1e(-) waves. Theoretical interrogations into correlations based on ring size and charge state are facilitated using values of the equilibrium potentials of these transitions, as well as their relative spacing. As the interaction free energies between the redox centres scale linearly with overall ring charge and in conjunction with fast intramolecular electron transfer (~10(7) s(-1)), these molecules can be considered as uniformly charged nanorings (diameter ~1-2 nm). PMID- 27554409 TI - Accurate first-principles structures and energies of diversely bonded systems from an efficient density functional. AB - One atom or molecule binds to another through various types of bond, the strengths of which range from several meV to several eV. Although some computational methods can provide accurate descriptions of all bond types, those methods are not efficient enough for many studies (for example, large systems, ab initio molecular dynamics and high-throughput searches for functional materials). Here, we show that the recently developed non-empirical strongly constrained and appropriately normed (SCAN) meta-generalized gradient approximation (meta-GGA) within the density functional theory framework predicts accurate geometries and energies of diversely bonded molecules and materials (including covalent, metallic, ionic, hydrogen and van der Waals bonds). This represents a significant improvement at comparable efficiency over its predecessors, the GGAs that currently dominate materials computation. Often, SCAN matches or improves on the accuracy of a computationally expensive hybrid functional, at almost-GGA cost. SCAN is therefore expected to have a broad impact on chemistry and materials science. PMID- 27554410 TI - Installing hydrolytic activity into a completely de novo protein framework. AB - The design of enzyme-like catalysts tests our understanding of sequence-to structure/function relationships in proteins. Here we install hydrolytic activity predictably into a completely de novo and thermostable alpha-helical barrel, which comprises seven helices arranged around an accessible channel. We show that the lumen of the barrel accepts 21 mutations to functional polar residues. The resulting variant, which has cysteine-histidine-glutamic acid triads on each helix, hydrolyses p-nitrophenyl acetate with catalytic efficiencies that match the most-efficient redesigned hydrolases based on natural protein scaffolds. This is the first report of a functional catalytic triad engineered into a de novo protein framework. The flexibility of our system also allows the facile incorporation of unnatural side chains to improve activity and probe the catalytic mechanism. Such a predictable and robust construction of truly de novo biocatalysts holds promise for applications in chemical and biochemical synthesis. PMID- 27554411 TI - Self-assembled molecular p/n junctions for applications in dye-sensitized solar energy conversion. AB - The achievement of long-lived photoinduced redox separation lifetimes has long been a central goal of molecular-based solar energy conversion strategies. The longer the redox-separation lifetime, the more time available for useful work to be extracted from the absorbed photon energy. Here we describe a novel strategy for dye-sensitized solar energy applications in which redox-separated lifetimes on the order of milliseconds to seconds can be achieved based on a simple toolkit of molecular components. Specifically, molecular chromophores (C), electron acceptors (A) and electron donors (D) were self-assembled on the surfaces of mesoporous, transparent conducting indium tin oxide nanoparticle (nanoITO) electrodes to prepare both photoanode (nanoITO|-A-C-D) and photocathode (nanoITO| D-C-A) assemblies. Nanosecond transient-absorption and steady-state photolysis measurements show that the electrodes function microscopically as molecular analogues of semiconductor p/n junctions. These results point to a new chemical strategy for dye-sensitized solar energy conversion based on molecular excited states and electron acceptors/donors on the surfaces of transparent conducting oxide nanoparticle electrodes. PMID- 27554412 TI - Kinetic pathway for interfacial electron transfer from a semiconductor to a molecule. AB - Molecular approaches to solar-energy conversion require a kinetic optimization of light-induced electron-transfer reactions. At molecular-semiconductor interfaces, this optimization has previously been accomplished through control of the distance between the semiconductor donor and the molecular acceptor and/or the free energy that accompanies electron transfer. Here we show that a kinetic pathway for electron transfer from a semiconductor to a molecular acceptor also exists and provides an alternative method for the control of interfacial kinetics. The pathway was identified by the rational design of molecules in which the distance and the driving force were held near parity and only the geometric torsion about a xylyl- or phenylthiophene bridge was varied. Electronic coupling through the phenyl bridge was a factor of ten greater than that through the xylyl bridge. Comparative studies revealed a significant bridge dependence for electron transfer that could not be rationalized by a change in distance or driving force. Instead, the data indicate an interfacial electron-transfer pathway that utilizes the aromatic bridge orbitals. PMID- 27554413 TI - Self-organized architectures from assorted DNA-framed nanoparticles. AB - The science of self-assembly has undergone a radical shift from asking questions about why individual components self-organize into ordered structures, to manipulating the resultant order. However, the quest for far-reaching nanomanufacturing requires addressing an even more challenging question: how to form nanoparticle (NP) structures with designed architectures without explicitly prescribing particle positions. Here we report an assembly concept in which building instructions are embedded into NPs via DNA frames. The integration of NPs and DNA origami frames enables the fabrication of NPs with designed anisotropic and selective interactions. Using a pre-defined set of different DNA framed NPs, we show it is possible to design diverse planar architectures, which include periodic structures and shaped meso-objects that spontaneously emerge on mixing of the different topological types of NP. Even objects of non-trivial shapes, such as a nanoscale model of Leonardo da Vinci's Vitruvian Man, can be self-assembled successfully. PMID- 27554414 TI - Wide-dynamic-range kinetic investigations of deep proton tunnelling in proteins. AB - Directional proton transport along 'wires' that feed biochemical reactions in proteins is poorly understood. Amino-acid residues with high pKa are seldom considered as active transport elements in such wires because of their large classical barrier for proton dissociation. Here, we use the light-triggered proton wire of the green fluorescent protein to study its ground-electronic-state proton-transport kinetics, revealing a large temperature-dependent kinetic isotope effect. We show that 'deep' proton tunnelling between hydrogen-bonded oxygen atoms with a typical donor-acceptor distance of 2.7-2.8 A fully accounts for the rates at all temperatures, including the unexpectedly large value (2.5 * 10(9) s(-1)) found at room temperature. The rate-limiting step in green fluorescent protein is assigned to tunnelling of the ionization-resistant serine hydroxyl proton. This suggests how high-pKa residues within a proton wire can act as a 'tunnel diode' to kinetically trap protons and control the direction of proton flow. PMID- 27554416 TI - Uuh? No. It's livermorium! PMID- 27554415 TI - Cell-sized asymmetric lipid vesicles facilitate the investigation of asymmetric membranes. AB - Asymmetric lipid giant vesicles have been used to model the biochemical reactions in cell membranes. However, methods for producing asymmetric giant vesicles lead to the inclusion of an organic solvent layer that affects the mechanical and physical characteristics of the membrane. Here we describe the formation of asymmetric giant vesicles that include little organic solvent, and use them to investigate the dynamic responses of lipid molecules in the vesicle membrane. We formed the giant vesicles via the inhomogeneous break-up of a lipid microtube generated by applying a jet flow to an asymmetric planar lipid bilayer. The asymmetric giant vesicles showed a lipid flip-flop behaviour in the membrane, superficially similar to the lipid flip-flop activity observed in apoptotic cells. In vitro synthesis of membrane proteins into the asymmetric giant vesicles revealed that the lipid asymmetry in bilayer membranes improves the reconstitution ratio of membrane proteins. Our asymmetric giant vesicles will be useful in elucidating lipid-lipid and lipid-membrane protein interactions involved in the regulation of cellular functions. PMID- 27554417 TI - Diagnosis of HCC for patients with cirrhosis using miRNA profiles of the tumor surrounding tissue - A statistical model based on stepwise penalized logistic regression. AB - The presence of hepatocellular carcinoma (HCC) is a significant complication of cirrhosis because it changes the prognosis and the treatment of the patients. By now, contrast-enhanced CT and MR scans are the most reliable tools for the diagnosis of HCC; however, in some cases, a biopsy of the tumor is necessary for the final diagnosis. The aim of the study was to develop a diagnostic tool using the microRNA (miRNA) profiles of the tissue surrounding the HCC tumor combined with clinical parameters in statistical models. At a transplantation setting, 32 patients with HCC and cirrhosis (B) were compared to 22 patients suffering from cirrhosis only (A). The diagnosis and exclusion of HCC was confirmed following the histopathological examination of the explanted liver. The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p<0.001) and showed higher levels of ALT (A: 0.76MUkat/l, B: 1.02MUkat/, p=0.006) and AFP (A: 5.8ng/ml, B: 70.3ng/ml, p<0.001), whereas the bilirubin levels were higher in the cirrhosis only group (p=0.002). Using age (cut-off 50.23years) and AFP (cut-off 4.2ng/ml) thresholds, the levels of expression of miR-1285-3p and miR-943 differentiated between the patients with HCC and cirrhosis from those with cirrhosis only with an accuracy of 96.3%. This is the first report about the use of stepwise penalized logistic regression and decision tree analyses of miRNA expressions in the tumor-surrounding tissue combined with clinical parameters for the diagnosis of HCC. PMID- 27554418 TI - Hippocampal PER1: a circadian sentinel controlling RSKy activity during memory formation. AB - Studies have demonstrated a pronounced dependence of memory formation on circadian time; however, the numerous mechanisms underlying this reliance are only beginning to be understood. While the 24-h cellular clock controls various aspects of hippocampal memory formation, its consolidation in particular (i.e., its conversion from short-term to long-term memory), appears to be heavily dependent on circadian activity in hippocampal neurons. Hippocampal memory consolidation requires phosphorylation of the cAMP Response Element-Binding protein, CREB, which upon phosphorylation promotes the transcription of genes necessary for long-term memory formation. Rhythmic cAMP/ERK-MAPK activity upstream of CREB is a necessary component. This Editorial highlights a study by Rawashdeh and coworkers, in which the authors establish the circadian clock gene Period1 (Per1) as a regulator of CREB phosphorylation in the mouse hippocampus, and thus reveal a functional link between circadian rhythms and learning efficiency. Read the highlighted article 'Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK' on page 731. PMID- 27554420 TI - Ductal carcinoma in situ: Is core needle biopsy ever enough? AB - INTRODUCTION: This study investigates the rate of histological underestimation of invasive breast carcinoma following diagnosis of ductal carcinoma in situ (DCIS) on a radiologically guided core needle biopsy, and factors that may influence this upgrade rate. METHODS: A retrospective review of the results of breast core biopsies performed between 1st January, 2005 and 2nd July, 2014 was conducted, and those with a diagnosis of DCIS were identified. Data including final excision pathology, lesion size, performing radiologist, core biopsy system and guidance method used were collected and included in the analysis. RESULTS: We report an overall upgrade rate to invasive cancer of 20.5% (95% CI = 16.1-24.9%). No statistically significant relationship was identified between biopsy systems used or clinicians performing the biopsies and the rate of upgrade to invasive cancer. Initially a statistically significant relationship was demonstrated between upgrade rates and lesion size, DCIS grade, as well as guidance method. Subsequent multivariable analysis showed no statistically significant relationship between guidance method and upgrade rates but a trend towards statistical significance (P < 0.1). CONCLUSION: Our recommendation is to inform women diagnosed with DCIS preoperatively in our programme, that there is a one in five chance the diagnosis will prove to be invasive cancer on definitive surgery. This is particularly important for women contemplating whether or not to undergo surgery for DCIS. Additionally, as the most significant predictor of upgrade rate demonstrated in this study is increasing lesion size, consideration should be given to increasing the number of core samples taken of larger lesions. PMID- 27554419 TI - Metadherin peptides containing CD4(+) and CD8(+) T cell epitopes as a therapeutic vaccine candidate against cancer. AB - The concept of peptide-based vaccines against cancer has made noteworthy progress. Metadherin (MTDH) overexpression and its role in the development of diverse cancers make it an attractive target for cancer immunotherapy. In the current study, six different T cell epitope prediction tools were run to identify MTDH peptides with multiple immunogenic regions. Further, molecular docking was performed to assess HLA-peptide binding interactions. Nine and eleven peptides fragments containing multiple CD8 (+) and CD4 (+) T-cell epitopes, ranging from 9 to 20 amino acids, respectively, were obtained using a consensus immunoinformatics approach. The three peptides that were finally identified as having overlapping CD4 (+) and CD8 (+) T- cell epitopes are ARLREMLSVGLGFLRTELG, FLLGYGWAAACAGAR, YIDDEWSGLNGLSSADP. These peptides were found to not only have multiple T cell epitopes but also to have binding affinity with wide HLA molecules. A molecular docking study revealed that the predicted immunogenic peptides (with single or multiple T cell epitopes) of MTDH have comparable binding energies with naturally bound peptides for both HLA classes I and II. Thus, these peptides have the potential to induce immune responses that could be considered for developing synthetic peptide vaccines against multiple cancers. PMID- 27554421 TI - Calmodulin EF-hand peptides as Ca2+ -switchable recognition tags. AB - Calmodulin is a representative calcium-binding protein comprised of four Ca2+ binding motifs with a helix-loop-helix structure (EF-hands). In this study, we clarified the potential of peptide segments derived from the third and fourth EF hands (EF3 and EF4) to act as recognition tags. Through an analysis of the mode of disulfide formation among cysteines inserted at the N- or C-terminus of these peptide segments, EF3 and EF4 peptides were suggested to form a heterodimer with a topology similar to that in the wild-type protein. Heterodimer formation was shown to be a function of the Ca2+ concentration, suggesting that these structures may be used as Ca2+ -switchable recognition tags. An example of an "EF tag" system involving the membrane fusion of liposomes decorated with EF3 and EF4 peptides is presented. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2016. PMID- 27554422 TI - Subclinical atrial fibrillation: A new entity and what it means? AB - New device technologies allow for detection of clinically silent atrial fibrillation. This new entity has been associated with increased risk for stroke, even if detected for only relatively brief time periods. Current practice guidelines do not provide recommendations on how to approach this new clinical entity. PMID- 27554423 TI - QRS complex waveform indicators of ventricular activation slowing: Simulation studies. AB - Diffuse or regional activation slowing in ventricular myocardium can result from different cardiac pathologies, such as left ventricular hypertrophy, ischemia or fibrosis. Altered ventricular activation sequence leads to deformations of the activation front and consequently to the changes in the QRS complex. Using a computer model we simulated the effect of slowed ventricular activation on the QRS waveform with a special interest in ECG changes which reproduce the ECG criteria of left ventricular hypertrophy (ECG-LVH). This paper describes results of a set of computer modeling experiments and discusses visual QRS patterns. Slowed ventricular activation in the whole left ventricle resulted in the prolongation of QRS duration, leftward shift of electrical axis, and increase in the QRS amplitude mainly in the precordial leads, having thus their main impact on simulated Sokolow-Lyon index and Cornell voltage. Slowed ventricular activation in the anteroseptal region resulted in a leftward shift of the electrical axis and increased values of ECG-LVH criteria seen in limb leads or in a combination with precordial leads (Gubner criterion, Cornell voltage). Transmural slowing and midwall slowing in two layers in the anteroseptal area led also to the QRS duration prolongation. Changes in QRS complex were more pronounced in the cases of transmural slowing as compared to the left ventricular midwall slowing. Using computer modeling, we showed that slowed ventricular activation is a potent determinant of QRS complex morphology and can mimic ECG patterns that are usually interpreted as the effect of left ventricular hypertrophy, i.e., increased left ventricular mass. These results contribute to understanding the variety of ECG finding documented in patients with LVH, considering not only anatomical enlargement but also the altered electrical properties of hypertrophied myocardium. PMID- 27554424 TI - Electrocardiographic predictors of mortality and sudden cardiac death in patients with end stage renal disease on hemodialysis. AB - Patients with end stage renal disease (ESRD) on hemodialysis experience a high incidence of cardiovascular mortality, and sudden cardiac death (SCD) accounts for approximately 25% of all deaths in this patient population. Despite this high risk of SCD, many non-invasive SCD risk stratification tools that are frequently applied to other patient populations (such as those with prior myocardial infarction and reduced left ventricular systolic function) may be less useful markers of increased SCD risk in ESRD. Improved SCD risk stratification tools for use specifically in patients on hemodialysis are therefore necessary to optimally target use of primary prevention interventions aimed at decreasing SCD incidence. Electrocardiography is an effective, non-invasive SCD risk stratification tool in hemodialysis patients. This article reviews data supporting the association between various ECG parameters (QT interval, spatial QRS-T angle, signal averaged ECG, heart rate variability, and T-wave alternans) and mortality/SCD in the dialysis population. Despite the association between abnormal ECG parameters and SCD, it remains unclear if these abnormal parameters (such as prolonged QT interval) are mechanistically related to SCD and/or ventricular arrhythmias, or if they are simply markers for more severe cardiac disease, such as left ventricular hypertrophy, that may independently predispose to SCD. Current obstacles that impair widespread implementation of ECG risk stratification in the hemodialysis population are also discussed. PMID- 27554425 TI - Genetic determinant of trabecular bone score (TBS) and bone mineral density: A bivariate analysis. AB - : This study sought to estimate the extent of genetic influence on the variation in trabecular bone score (TBS). We found that genetic factors accounted for ~45% of variance in TBS, and that the co-variation between TBS and bone density is partially determined by genetic factors. INTRODUCTION: Trabecular bone score has emerged as an important predictor of fragility fracture, but factors underlying the individual differences in TBS have not been explored. In this study, we sought to determine the genetic contribution to the variation of TBS in the general population. METHODS: The study included 556 women and 189 men from 265 families. The individuals aged 53years (SD 11). We measured lumbar spine bone mineral density (BMD; Hologic Horizon) and then derived the TBS from the same Hologic scan where BMD was derived. A biometric model was applied to the data to partition the variance of TBS into two components: one due to additive genetic factors, and one due to environmental factors. The index of heritability was estimated as the ratio of genetic variance to total variance of a trait. Bivariate genetic analysis was conducted to estimate the genetic correlation between TBS and BMD measurements. RESULTS: TBS was strongly correlated with lumbar spine BMD (r=0.73; P<0.001). On average TBS in men was higher than women, after adjusting age and height which are significantly associated with both TBS and lumbar spine BMD. The age and height adjusted index of heritability of TBS was 0.46 (95% CI, 0.39-0.54), which was not much different from that of LSBMD (0.44; 95% CI, 0.31-0.55). Moreover, the genetic correlation between TBS and LSBMD was 0.35 (95% CI, 0.21-0.46), between TBS and femoral neck BMD was 0.21 (95% CI, 0.10-0.33). CONCLUSIONS: Approximately 45% of the variance in TBS is under genetic influence, and this effect magnitude is similar to that of lumbar spine BMD. This finding provides a scientific justification for the search for specific genetic variants that may be associated with TBS and fracture risk. PMID- 27554426 TI - Areal and volumetric bone mineral density and risk of multiple types of fracture in older men. AB - Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7years of follow-up. Men answered questionnaires about fractures every 4months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24-3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment. PMID- 27554427 TI - Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats. AB - BACKGROUND: Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear. OBJECTIVES: To investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE). METHODS: Male Zucker fatty rats were randomized distributed into 4 groups (n=8): normoprotein+sedentary; normoprotein+exercise; moderately high-protein+sedentary, and moderately high-protein+exercise. Training groups conducted an IASE program, 5days/week for 2months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography. RESULTS: Femur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, p<0.05), whereas plasma alkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, p<0.01). Final body weight and alkaline phosphatase levels were lower in the exercise compared to the sedentary (both, p<0.05), whereas femur length and weight, aminoterminal propeptides of type I procollagen and C terminal telopeptides of type I collagen concentrations, and cortical TV and BV were higher in the exercise compared to the sedentary groups (all, p<0.05). CONCLUSION: The combination of interventions may be effective to enhance trabecular bone microarchitecture and BMD, and has a partial impact on cortical bone in obese rats. Nevertheless, they do not induce any alteration on the bone turnover markers. PMID- 27554428 TI - Parathyroid hormone induces expression and proteolytic processing of Rankl in primary murine osteoblasts. AB - Rankl, the major pro-osteoclastogenic cytokine, is synthesized as a transmembrane protein that can be cleaved by specific endopeptidases to release a soluble form (sRankl). We have previously reported that interleukin-33 (IL-33) induces expression of Tnfsf11, the Rankl-encoding gene, in primary osteoblasts, but we failed to detect sRankl in the medium. Since we also found that PTH treatment caused sRankl release in a similar experimental setting, we directly compared the influence of the two molecules. Here we show that treatment of primary murine osteoblasts with PTH causes sRankl release into the medium, whereas IL-33 only induces Tnfsf11 expression. This difference was not explainable by alternative splicing or by PTH-specific induction of endopeptidases previously shown to facilitate Rankl processing. Since sRankl release after PTH administration was blocked in the presence a broad-spectrum matrix metalloprotease inhibitor, we applied genome-wide expression analyses to identify transcriptional targets of PTH in osteoblasts. We thereby confirmed some of the effects of PTH established in other systems, but additionally identified few PTH-induced genes encoding metalloproteases. By comparing expression of these genes following administration of IL-33, PTH and various other Tnfsf11-inducing molecules, we observed that PTH was the only molecule simultaneously inducing sRankl release and Adamts1 expression. The functional relevance of the putative influence of PTH on Rankl processing was further confirmed in vivo, as we found that daily injection of PTH into wildtype mice did not only increase bone formation, but also osteoclastogenesis and sRankl concentrations in the serum. Taken together, our findings demonstrate that transcriptional effects on Tnfsf11 expression do not generally trigger sRankl release and that PTH has a unique activity to promote the proteolytic processing of Rankl. PMID- 27554430 TI - Why do we have the kidney allocation system we have today? A history of the 2014 kidney allocation system. AB - "Those who do not know the past are destined to repeat it". The current system for the allocation of deceased donor kidneys that was implemented in December 2014 (termed the kidney allocation system (KAS)) was the culmination of a decade long process. Thus, many people involved in transplantation today may not be aware of the underlying concepts and early debates that resulted in KAS. Others who were involved might not remember the details (or have chosen to forget). The goal of this manuscript is to outline the history of the process in order to shed light on why KAS has its current format. PMID- 27554429 TI - Cerebral Perfusion Changes in Post-Concussion Syndrome: A Prospective Controlled Cohort Study. AB - The biology of post-concussive symptoms is unclear. Symptoms are often increased during activities, and have been linked to decreased cerebrovascular reactivity and perfusion. The aim of this study was to examine cerebral blood flow (CBF) in children with different clinical recovery patterns following mild traumatic brain injury (mTBI). This was a prospective controlled cohort study of children with mTBI (ages 8 to 18 years) who were symptomatic with post-concussive symptoms at one month post-injury (symptomatic, n = 27) and children who had recovered quickly (asymptomatic, n = 24). Pseudo continuous arterial spin labeling magnetic resonance imaging (MRI) was used to quantify CBF. The mTBI groups were imaged at 40 days post-injury. Global and regional CBF were compared with healthy controls of similar age and sex but without a history of mTBI (n = 21). Seventy-two participants (mean age: 14.1 years) underwent neuroimaging. Significant differences in CBF were found: global CBF was higher in the symptomatic group and lower in the asymptomatic group compared with controls, (F(2,69) 9.734; p < 0.001). Post-injury symptom score could be predicted by pre-injury symptoms and CBF in presence of mTBI (adjusted R2 = 0.424; p < 0.001). Altered patterns of cerebral perfusion are seen following mTBI and are associated with the recovery trajectory. Symptomatic children have higher CBF. Children who "recovered" quickly, have decreased CBF suggesting that clinical recovery precedes the cerebral recovery. Further longitudinal studies are required to determine if these perfusion patterns continue to change over time. PMID- 27554432 TI - Erratum. PMID- 27554431 TI - Lefty Glycoproteins in Human Embryonic Stem Cells: Extracellular Delivery Route and Posttranslational Modification in Differentiation. AB - Lefty is a member of transforming growth factor-beta (TGF-beta) superfamily and a potent antagonist of the TGF-beta/Nodal/Activin signaling pathway. Lefty is critical in sustaining self-renewal/pluripotency status, and implicated in the differentiation of embryonic stem cells (ESCs). However, emerging studies depict Lefty as a multifaceted protein involved in myriad cellular events. Lefty proteins (human Lefty A and B) are secreted glycoproteins, but their mode of secretion and the significance of their "glycan" moiety remain mostly unexplored. By employing an in vitro system of human ESCs (hESCs), we observed that Lefty protein(s) are encased in exosomes for extracellular release. The exosomal- and cell-associated Lefty diverge in their proteolytic processing, and possess N glycan structures of high mannose and complex nature. Differentiation of hESCs to mesenchymal cells (MSCs) or neuronal progenitor cells (NPCs) entails distinct changes in the Lefty A/Lefty B gene(s), and protein expression. Specifically, the proteolytic cleavage and N-glycan composition of the cell-associated and exosomal Lefty differ in the differentiated progenies. These modifications affected Lefty's inhibitory effect on Nodal signaling in aggressive melanoma cells. The microheterogeneity in the processing and glycosylation of Lefty protein(s) between hESCs, MSCs, and NPCs could present efficient means of diversifying the endogenous functions of Lefty. Whether Lefty's diverse functions in embryonic patterning, as well as its diffusion range in the extracellular environment, are similarly affected remains to be determined. Our studies underscore the potential relevance of Lefty-packaged exosomes for combating debilitating diseases such as cancer. PMID- 27554433 TI - Meta-Analysis and Systematic Review of Neural Stem Cells therapy for experimental ischemia stroke in preclinical studies. AB - To evaluate the preclinical studies using NSCs transplantation therapy for experimental ischemic stroke, and determine the effect size of NSCs therapy and the correlations between different clinical measures. We firstly searched literatures to identify studies of NSCs therapy in animal cerebral ischemia models, and then calculated the quality score of studies, assessed the effect size of NSCs therapy relative to behavioral and histologic endpoints by meta analysis. A total of 37 studies and 54 independent treated interventions were used for systematic review and meta-analysis. The median quality score was 5 of 10. 36 studies (53 intervention arms) reported functional outcome, 22 studies (34 intervention arms) reported structural outcome. After adjusted by subgroup and sensitivity analysis, the mean effect sizes were improved by 1.35 for mNSS, 1.84 for rotarod test, 0.61 for cylinder test, and 0.84 for infarct volume. Furthermore, effect size had a certain interaction with clinical variables, for example early NSCs therapy etc. In this preclinical studies, we demonstrated that transplanted NSCs significantly improved outcomes (both functional and structural outcome) in ischemic stroke. It is suggested that future preclinical animal model studies of stroke should improve study quality validity and reduce potentially confounded publication bias. PMID- 27554434 TI - Good Cell Culture Practice for stem cells and stem-cell-derived models. AB - The first guidance on Good Cell Culture Practice (GCCP) dates back to 2005. This document expands this to include aspects of quality assurance for in vitro cell culture focusing on the increasingly diverse cell types and culture formats used in research, product development, testing and manufacture of biotechnology products and cell-based medicines. It provides a set of basic principles of best practice that can be used in training new personnel, reviewing and improving local procedures, and helping to assure standard practices and conditions for the comparison of data between laboratories and experimentation performed at different times. This includes recommendations for the documentation and reporting of culture conditions. It is intended as guidance to facilitate the generation of reliable data from cell culture systems, and is not intended to conflict with local or higher level legislation or regulatory requirements. It may not be possible to meet all recommendations in this guidance for practical, legal or other reasons. However, when it is necessary to divert from the principles of GCCP, the risk of decreasing the quality of work and the safety of laboratory staff should be addressed and any conclusions or alternative approaches justified. This workshop report is considered a first step toward a revised GCCP 2.0. PMID- 27554436 TI - From Social Exclusion to Supported Inclusion: Adults with Intellectual Disability Discuss Their Lived Experiences of a Structured Social Group. AB - BACKGROUND: People with intellectual disability often have few friends and experience social exclusion. Recognising this gap, supported social groups with the aim of inclusion and interdependence were created by a supported employment provider. METHODS: Interviews were undertaken with 10 adults with intellectual disability exploring their lived experiences of a supported social group. Data were analysed using descriptive phenomenology. RESULTS: Two themes emerged (i) supported engagement fosters wellbeing, and (ii) developing social belonging and connectedness. Participants not only acknowledged the support that they needed to participate, but also that the social group had changed their lives in many ways. CONCLUSIONS: Adults with intellectual disability want to socialise, have friends and be part of their community. For this to be achieved, they recognise the need to seek some form of support. With appropriate and targeted support, adults with intellectual disability can move from social exclusion towards supported inclusion and experience richer lives. PMID- 27554437 TI - A Simple Primary Amide for the Selective Recovery of Gold from Secondary Resources. AB - Waste electrical and electronic equipment (WEEE) such as mobile phones contains a plethora of metals of which gold is by far the most valuable. Herein a simple primary amide is described that achieves the selective separation of gold from a mixture of metals typically found in mobile phones by extraction into toluene from an aqueous HCl solution; unlike current processes, reverse phase transfer is achieved simply using water. Phase transfer occurs by dynamic assembly of protonated and neutral amides with [AuCl4 ](-) ions through hydrogen bonding in the organic phase, as shown by EXAFS, mass spectrometry measurements, and computational calculations, and supported by distribution coefficient analysis. The fundamental chemical understanding gained herein should be integral to the development of metal-recovery processes, in particular through the use of dynamic assembly processes to build complexity from simplicity. PMID- 27554435 TI - Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties. AB - Staphylokinase (Sak) is a plasminogen activator protein that is secreted by many Staphylococcus aureus strains. Sak also offers protection by binding and inhibiting specific antimicrobial peptides (AMPs). Here, we evaluate Sak as a more general interaction partner for AMPs. Studies with melittin, mCRAMP, tritrpticin and bovine lactoferricin indicate that the truncation of the first ten residues of Sak (SakDeltaN10), which occurs in vivo and uncovers important residues in a bulge region, improves its affinity for AMPs. Melittin and mCRAMP have a lower affinity for SakDeltaN10, and in docking studies, they bind to the N terminal segment and bulge region of SakDeltaN10. By comparison, lactoferricin and tritrpticin form moderately high affinity 1:1 complexes with SakDeltaN10 and their cationic residues form several electrostatic interactions with the protein's alpha-helix. Overall, our work identifies two distinct AMP binding surfaces on SakDeltaN10 whose occupation would lead to either inhibition or promotion of its plasminogen activating properties. PMID- 27554438 TI - Plasma copeptin and functional outcome in patients with ischemic stroke and type 2 diabetes. AB - BACKGROUND: The activation of the arginine vasopressin system may be involved in the pathology of stroke and diabetes. In this study, we therefore evaluated the short-term prognostic value of early measurement of plasma copeptin levels in Chinese patients with type 2 diabetes mellitus (T2DM) and acute ischemic stroke (AIS). METHODS: From July 2014 to June 2015, all T2DM patients with first-ever AIS were included. Plasma levels of copeptin were tested at admission. The prognostic value of copeptin to predict the functional outcome and mortality 3months after stroke was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. RESULTS: We recorded 247 stroke patients with T2DM. The copeptin levels were obtained in those patients with a median value of 14.3pmol/L (IQR, 9.5-17.1pmol/L). At 3-month follow-up, a favorable functional outcome was found in 86 patients (34.8%). Plasma copeptin levels in patients with an unfavorable outcome were significantly greater than those in patients with a favorable outcome (16.2 [IQR, 12.2-20.3] vs. 12.4 [IQR, 8.6-15.2] pmol/L; Z=5.399; P<0.0001). In univariate logistic regression analysis, with an unadjusted OR of 1.123 (95% CI, 1.072-1.177, P<0.001), copeptin had a strong association with unfavorable functional outcome. In multivariate analyses, a copeptin level in the highest inter-quartile (>17.1pmol/L) was associated with a higher risk of unfavorable functional outcome (OR=4.62; 95% CI=2.63-9.21; P<0.001). After adjusting for other outcome predictors, a copeptin level in the highest inter-quartile (>17.1pmol/L) was associated with a higher risk of mortality (OR=5.12; 95% CI=2.20-11.38; P<0.001). CONCLUSION: Our study suggested that copeptin levels may reliably predict short-term stroke prognosis at its onset in Chinese patients with T2DM and stroke. PMID- 27554439 TI - Allergy to antibiotics in children: an overestimated problem. AB - Antibiotics are the most prescribed drugs for children, and a relevant number of prescriptions are associated with the emergence of adverse events. Allergic reactions are the most frequently reported adverse events, with an incidence of up to 10% of all prescriptions. However, literature analysis has shown that allergy to antibiotics is generally overdiagnosed in children because in most cases the diagnosis is based only on the clinical history without a full allergy work-up. Consequently, children are often improperly deprived of narrow-spectrum antibiotics because of a suspected allergy to these drugs. beta-Lactams, mainly penicillins, are more frequently involved as a cause of allergy to antibiotics, although allergic problems are reported for most of the antibiotic classes. Accurate diagnosis is essential for a precise definition of determination of allergy to a given drug. Diagnosis has to be based on history, laboratory tests and, when possible, on in vitro and drug provocation tests. Unfortunately, the allergological work-up is well structured only for beta-lactam antibiotics, whereas for non-beta-lactams few studies are available, with very limited experience in children. The main aim of this paper is to discuss the real relevance of allergy to antibiotics in children in order to provide physicians with the knowledge needed to establish an appropriate diagnostic allergy work-up and to make better use of antibiotic therapy. PMID- 27554440 TI - Ex vivo efficacy of gemifloxacin in experimental keratitis induced by methicillin resistant Staphylococcus aureus. AB - In recent years, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) strains has been observed in ocular infections. Resistance of MRSA to second- and third-generation fluoroquinolones has increased interest in the fourth-generation fluoroquinolones. In this study, the antibacterial activity of gemifloxacin against MRSA ocular isolates in vitro and in a modified ex vivo rabbit keratitis model was investigated. In vitro susceptibility test results indicated that the minimum inhibitory concentrations (MICs) of gemifloxacin were lower than the MICs of other fluoroquinolones, including moxifloxacin (MIC50 range, 0.016-0.032 ug/mL; MIC90 range, 0.047-0.094 ug/mL). Results from the ex vivo keratitis model showed a statistically significant decrease in MRSA counts (0.5-2 log10 CFU/g; P <0.05) in corneas treated with 0.3% gemifloxacin every 30 min for 7 h. Moreover, the dose-response effect of different concentrations of gemifloxacin (3-3000 ug/mL) demonstrated that a dose of 30 ug/mL had the same efficacy as the highest dose of 3000 ug/mL against all S. aureus strains. Possibly, gemifloxacin reached a steady-state level in the cornea, as the fourth generation fluoroquinolones have better anterior chamber penetration. This study demonstrated that 0.3% gemifloxacin ophthalmic solution may be an effective topical therapy for the treatment of MRSA keratitis. In addition, this reproducible, ethical and economic ex vivo infection model can be used as a mechanistically-based alternative to in vivo animal testing, bridging the gap between in vitro and in vivo results. PMID- 27554441 TI - Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT. AB - STUDY QUESTION: Does embryo culture medium influence pregnancy and perinatal outcome in IVF? SUMMARY ANSWER: Embryo culture media used in IVF affect treatment efficacy and the birthweight of newborns. WHAT IS KNOWN ALREADY: A wide variety of culture media for human preimplantation embryos in IVF/ICSI treatments currently exists. It is unknown which medium is best in terms of clinical outcomes. Furthermore, it has been suggested that the culture medium used for the in vitro culture of embryos affects birthweight, but this has never been demonstrated by large randomized trials. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter, double-blind RCT comparing the use of HTF and G5 embryo culture media in IVF. Between July 2010 and May 2012, 836 couples (419 in the HTF group and 417 in the G5 group) were included. The allocated medium (1:1 allocation) was used in all treatment cycles a couple received within 1 year after randomization, including possible transfers with frozen-thawed embryos. The primary outcome was live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples that were scheduled for an IVF or an ICSI treatment at one of the six participating centers in the Netherlands or their affiliated clinics. MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rate was higher, albeit nonsignificantly, in couples assigned to G5 than in couples assigned to HTF (44.1% (184/417) versus 37.9% (159/419); RR: 1.2; 95% confidence interval (CI): 0.99-1.37; P = 0.08). Number of utilizable embryos per cycle (2.8 +/- 2.3 versus 2.3 +/- 1.8; P < 0.001), implantation rate after fresh embryo transfer (20.2 versus 15.3%; P < 0.001) and clinical pregnancy rate (47.7 versus 40.1%; RR: 1.2; 95% CI: 1.02-1.39; P = 0.03) were significantly higher for couples assigned to G5 compared with those assigned to HTF. Of the 383 live born children in this trial, birthweight data from 380 children (300 singletons (G5: 163, HTF: 137) and 80 twin children (G5: 38, HTF: 42)) were retrieved. Birthweight was significantly lower in the G5 group compared with the HTF group, with a mean difference of 158 g (95% CI: 42-275 g; P = 0.008). More singletons were born preterm in the G5 group (8.6% (14/163) versus 2.2% (3/137), but singleton birthweight adjusted for gestational age and gender (z-score) was also lower in the G5 than in the HTF group (-0.13 +/- 0.08 versus 0.17 +/- 0.08; P = 0.008). LIMITATIONS, REASONS FOR CAUTION: This study was powered to detect a 10% difference in live births while a smaller difference could still be clinically relevant. The effect of other culture media on perinatal outcome remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture media used in IVF affect not only treatment efficacy but also perinatal outcome. This suggests that the millions of human embryos that are cultured in vitro each year are sensitive to their environment. These findings should lead to increased awareness, mechanistic studies and legislative adaptations to protect IVF offspring during the first few days of their existence. STUDY FUNDING/COMPETING INTERESTS: This project was partly funded by The NutsOhra foundation (Grant 1203-061) and March of Dimes (Grant 6 FY13-153). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: NTR1979 (Netherlands Trial Registry). TRIAL REGISTRATION DATE: 1 September 2009. DATE OF FIRST PATIENT'S ENROLMENT: 18 July 2010. PMID- 27554442 TI - Time to take human embryo culture seriously. AB - STUDY QUESTION: Is it important that end-users know the composition of human embryo culture media? SUMMARY ANSWER: We argue that there is as strong case for full transparency concerning the composition of embryo culture media intended for human use. WHAT IS KNOWN ALREADY: Published data suggest that the composition of embryo culture media may influence the phenotype of the offspring. STUDY DESIGN, SIZE, DURATION: A review of the literature was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data concerning the potential effects on embryo development of culture media were assessed and recommendations for users made. MAIN RESULTS AND THE ROLE OF CHANCE: The safety of ART procedures, especially with respect to the health of the offspring, is of major importance. There are reports from the literature indicating a possible effect of culture conditions, including culture media, on embryo and fetal development. Since the introduction of commercially available culture media, there has been a rapid development of different formulations, often not fully documented, disclosed or justified. There is now evidence that the environment the early embryo is exposed to can cause reprogramming of embryonic growth leading to alterations in fetal growth trajectory, birthweight, childhood growth and long-term disease including Type II diabetes and cardiovascular problems. The mechanism for this is likely to be epigenetic changes during the preimplantation period of development. In the present paper the ESHRE working group on culture media summarizes the present knowledge of potential effects on embryo development related to culture media, and makes recommendations. LIMITATIONS, REASONS FOR CAUTION: There is still a need for large prospective randomized trials to further elucidate the link between the composition of embryo culture media used and the phenotype of the offspring. We do not presently know if the phenotypic changes induced by in vitro embryo culture represent a problem for long-term health of the offspring. WIDER IMPLICATIONS OF THE FINDINGS: Published data indicate that there is a strong case for demanding full transparency concerning the compositions of and the scientific rationale behind the composition of embryo culture media. STUDY FUNDING/COMPETING INTERESTS: This work was funded by The European Society for Human Reproduction and Embryology. No competing interests to declare. PMID- 27554443 TI - Peanut butter. PMID- 27554444 TI - Synthesis, biological evaluation and molecular modeling study of some new methoxylated 2-benzylthio-quinazoline-4(3H)-ones as nonclassical antifolates. AB - A new series of 2,3,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 28 and 61 proved to be active DHFR inhibitors with IC50 0.02 and 0.01MUM, respectively. Molecular modeling studies concluded that recognition with the key amino acid Phe34 is essential for binding and hence DHFR inhibition. Compounds 34, 56 and 66 showed broad spectrum antimicrobial activity comparable to Gentamicin and Ciprofloxacin. Compounds 40 and 64 showed broad spectrum antitumor activity toward several tumor cell lines and proved to be 10 fold more active than 5-FU, with GI50 MG-MID values of 2.2 and 2.4MUM, respectively. PMID- 27554445 TI - Characterization of 3,3-dimethyl substituted N-aryl piperidines as potent microsomal prostaglandin E synthase-1 inhibitors. AB - Here we report on novel, potent 3,3-dimethyl substituted N-aryl piperidine inhibitors of microsomal prostaglandin E synthases-1(mPGES-1). Example 14 potently inhibited PGE2 synthesis in an ex vivo human whole blood (HWB) assay with an IC50 of 7nM. In addition, 14 had no activity in human COX-1 or COX-2 assays at 30MUM, and failed to inhibit human mPGES-2 at 62.5MUM in a microsomal prep assay. These data are consistent with selective mPGES-1-mediated reduction of PGE2. In dog, 14 had oral bioavailability (74%), clearance (3.62mL/(min*kg)) and volume of distribution (Vd,ss=1.6L/kg) values within our target ranges. For these reasons, 14 was selected for further study. PMID- 27554446 TI - Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase. AB - Protein tyrosine phosphatases (PTPs) play key roles in many physiological processes, including cell proliferation, differentiation, immune responses and neural activities. Inappropriate regulation of the PTP activity could lead to human diseases, such as cancer or diabetes. Functional studies of PTP can be greatly facilitated by chemical probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. Here, we characterize compound E4 as a new class of PTP activity probes. Compound E4 inactivate STEP in a time- and concentration-dependent fashion. Further study showed that compound E4 inhibits a series of PTPs in a time dependent manner, whereas it shows little or no inhibition toward metal dependent protein phosphatases. Collectively, this new identified covalent inhibitor of PTPs has the potential to be developed to an active site Cys directed PTP probes to study the active properties of the PTPs in cell signaling. PMID- 27554448 TI - New route for hollow materials. AB - Hollow micro/nano structures form an important family of functional materials. We have used the thermal oxidation process combined with the passage of electric current during a structural phase transition to disclose a colossal mass diffusion transfer of Ti ions. This combination points to a new route for fabrication of hollow materials. A structural phase transition at high temperature prepares the stage by giving mobility to Ti ions and releasing vacancies to the system. The electric current then drives an inward delocalization of vacancies, condensing into voids, and finally turning into a big hollow. This strong physical phenomenon leading to a colossal mass transfer through ionic diffusion is suggested to be driven by a combination of phase transition and electrical current followed by chemical reaction. We show this phenomenon for Ti leading to TiO2 microtube formation, but we believe that it can be used to other metals undergoing structural phase transition at high temperatures. PMID- 27554447 TI - Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation. AB - The intracellular Raf-Erk signaling pathway is activated during neural stem cell (NSC) proliferation, and neuronal and astrocytic differentiation. A key question is how this signal can evoke multiple and even opposing NSC behaviors. We show here, using a constitutively active Raf (ca-Raf), that Raf-Erk activation in NSCs induces neuronal differentiation in a cell-autonomous manner. By contrast, it causes NSC proliferation and the formation of astrocytes in an extrinsic autocrine/paracrine manner. Thus, treatment of NSCs with medium (CM) conditioned in ca-Raf-transduced NSCs (Raf-CM; RCM) became activated to form proliferating astrocytes resembling radial glial cells (RGCs) or adult-type NSCs. Infusion of Raf-CM into injured mouse brains caused expansion of the NSC population in the subventricular zone, followed by the formation of new neurons that migrated to the damaged site. Our study shows an example how molecular mechanisms dissecting NSC behaviors can be utilized to develop regenerative therapies in brain disorders. PMID- 27554450 TI - Proteins behaving badly. Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting. AB - The chief and largely terminal element of normal blood clotting is considered to involve the polymerisation of the mainly alpha-helical fibrinogen to fibrin, with a binding mechanism involving 'knobs and holes' but with otherwise little change in protein secondary structure. We recognise, however, that extremely unusual mutations or mechanical stressing can cause fibrinogen to adopt a conformation containing extensive beta-sheets. Similarly, prions can change morphology from a largely alpha-helical to largely beta-sheet conformation, and the latter catalyses both the transition and the self-organising polymerisation of the beta sheet structures. Many other proteins can also do this, where it is known as amyloidogenesis. When fibrin is formed in samples from patients harbouring different diseases it can have widely varying diameters and morphologies. We here develop the idea, and summarise the evidence, that in many cases the anomalous fibrin fibre formation seen in such diseases actually amounts to amyloidogenesis. In particular, fibrin can interact with the amyloid-beta (Abeta) protein that is misfolded in Alzheimer's disease. Seeing these unusual fibrin morphologies as true amyloids explains a great deal about fibrin(ogen) biology that was previously opaque, and provides novel strategies for treating such coagulopathies. The literature on blood clotting can usefully both inform and be informed by that on prions and on the many other widely recognised (beta-)amyloid proteins. A preprint has been lodged in bioRxiv (Kell and Pretorius, 2016). PMID- 27554449 TI - Are aberrant phase transitions a driver of cellular aging? AB - Why do cells age? Recent advances show that the cytoplasm is organized into many membrane-less compartments via a process known as phase separation, which ensures spatiotemporal control over diffusion-limited biochemical reactions. Although phase separation is a powerful mechanism to organize biochemical reactions, it comes with the trade-off that it is extremely sensitive to changes in physical chemical parameters, such as protein concentration, pH, or cellular energy levels. Here, we highlight recent findings showing that age-related neurodegenerative diseases are linked to aberrant phase transitions in neurons. We discuss how these aberrant phase transitions could be tied to a failure to maintain physiological physical-chemical conditions. We generalize this idea to suggest that the process of cellular aging involves a progressive loss of the organization of phase-separated compartments in the cytoplasm. PMID- 27554451 TI - The GCKR Gene Polymorphism rs780094 is a Risk Factor for Gestational Diabetes in a Brazilian Population. AB - BACKGROUND: The glucokinase regulatory protein (GCKR) regulates the activity of the glucokinase (GCK), which plays a key role in glucose homeostasis. Genetic variants in GCK have been associated with diabetes and gestational diabetes (GDM). Due to the relationship between GCKRP and GCK, polymorphisms in GCKR are also candidates for genetic association with GDM. The aim of this study was to evaluate the association between the GCKR rs780094 polymorphism and GDM in a Brazilian population. METHODS: 252 unrelated Euro-Brazilian pregnant women were classified as control (healthy pregnant women, n = 125) and GDM (pregnant women with GDM, n = 127) age-matched groups. Clinical and anthropometric data were obtained from all subjects. The GCKR rs780094 polymorphism was genotyped using fluorescent probes (TaqMan(r) , code C_2862873_10). RESULTS: Both groups were in Hardy-Weinberg equilibrium. The GCKR rs780094 polymorphism was associated with GDM in codominant and dominant models (P = 0.022 and P = 0.010, respectively). The minor allele (T) frequency for the control group in the study was 38.4% (95% CI: 32-44%), similar to frequencies reported for other Caucasian populations. CONCLUSION: Carriers of the C allele of rs780094 were 1.41 (odds ratio, 95% CI, 0.97-2.03) times more likely to develop GDM. PMID- 27554453 TI - From greening to browning: Catchment vegetation development and reduced S deposition promote organic carbon load on decadal time scales in Nordic lakes. AB - Increased concentrations of dissolved organic carbon (DOC), often labelled "browning", is a current trend in northern, particularly boreal, freshwaters. The browning has been attributed to the recent reduction in sulphate (S) deposition during the last 2 to 3 decades. Over the last century, climate and land use change have also caused an increasing trend in vegetation cover ("greening"), and this terrestrially fixed carbon represents another potential source for export of organic carbon to lakes and rivers. The impact of this greening on the observed browning of lakes and rivers on decadal time scales remains poorly investigated, however. Here, we explore time-series both on water chemistry and catchment vegetation cover (using NDVI as proxy) from 70 Norwegian lakes and catchments over a 30-year period. We show that the increase in terrestrial vegetation as well as temperature and runoff significantly adds to the reduced SO4-deposition as a driver of freshwater DOC concentration. Over extended periods (centuries), climate mediated changes in vegetation cover may cause major browning of northern surface waters, with severe impact on ecosystem productivity and functioning. PMID- 27554452 TI - Epilepsy due to mutations in the mitochondrial polymerase gamma (POLG) gene: A clinical and molecular genetic review. AB - We performed a systematic review of the clinical, molecular, and biochemical features of polymerase gamma (POLG)-related epilepsy and current evidence on seizure management. Patients were identified from a combined electronic search of articles using Ovid Medline and Scopus databases, published from January 2000 to January 2015. Only patients with a confirmed genetic diagnosis of POLG mutations were considered. Seventy-two articles were included for analysis. We identified 128 pathogenic variants in 372 patients who had POLG-related epilepsy. Among these, 84% of the cases harbored at least one of these pathogenic variants: p.Ala467Thr, p.Trp748Ser, and p.Gly848Ser. A bimodal distribution of disease onset was present in early childhood (<5 years) and adolescence; female patients had a later presentation than male patients (median age 4.00 vs. 1.83 years, p value = 0.041). Focal-onset seizure including convulsive, myoclonus, and occipital seizures was common at the outset and was refractory to pharmacotherapy. We confirmed that homozygous pathogenic variants located in the linker region of POLG were associated with later age of onset and longer survival compared to compound heterozygous variants. In addition, biochemical and molecular heterogeneities in different tissues were frequently observed. POLG related epilepsy is clinically heterogeneous, and the prognosis is, in part, influenced by the location of the variants in the gene and the presence of hepatic involvement. Normal muscle and fibroblast studies do no exclude the diagnosis of POLG-related mitochondrial disease and direct sequencing of the POLG gene should be the gold standard when investigating suspected cases. PMID- 27554454 TI - Synthesis, Properties, and Two-Dimensional Adsorption Characteristics of [6]Hexahelicene-7-carboxylic acid. AB - A convergent synthesis of racemic [6]hexahelicene-7-carboxylic acid by cross coupling of a bicyclic and a tricyclic component is described. A metal-catalyzed ring-closure is also a fundamental component of the synthetic approach. Scanning tunneling microscopy (STM) measurements of the racemate self-assembled on Au(111) at liquid-solid interface revealed the formation of ordered racemic 2D crystals. PMID- 27554455 TI - Recent advances and perspectives in topical oral anesthesia. AB - INTRODUCTION: Topical anesthesia is widely used in dentistry to reduce pain caused by needle insertion and injection of the anesthetic. However, successful anesthesia is not always achieved using the formulations that are currently commercially available. As a result, local anesthesia is still one of the procedures that is most feared by dental patients. Drug delivery systems (DDSs) provide ways of improving the efficacy of topical agents. Areas covered: An overview of the structure and permeability of oral mucosa is given, followed by a review of DDSs designed for dental topical anesthesia and their related clinical trials. Chemical approaches to enhance permeation and anesthesia efficacy, or to promote superficial anesthesia, include nanostructured carriers (liposomes, cyclodextrins, polymeric nanoparticle systems, solid lipid nanoparticles, and nanostructured lipid carriers) and different pharmaceutical dosage forms (patches, bio- and mucoadhesive systems, and hydrogels). Physical methods include pre-cooling, vibration, iontophoresis, and microneedle arrays. Expert opinion: The combination of different chemical and physical methods is an attractive option for effective topical anesthesia in oral mucosa. This comprehensive review should provide the readers with the most relevant options currently available to assist pain-free dental anesthesia. The findings should be considered for future clinical trials. PMID- 27554456 TI - Identification and Validation of Gene Expression Pattern and Signature in Patients with Immune Thrombocytopenia. AB - In the present study, we sought to define genes associated with immune thrombocytopenia (ITP). Microarray analysis revealed that of 1002 genes associated with ITP, 309 genes had downregulated expression and 693 genes had upregulated expression in patients with ITP. Gene set enrichment analysis revealed that 11 pathways were positively correlated to ITP, such as type I diabetes mellitus, intestinal immune network for IgA production, and oxidative phosphorylation. The messenger RNA expression levels of the indicated genes, including HLA-DRB5, IGHV3-66, IFI27, FAM212A, PLD5, tumor necrosis factor (TNF) alpha, interferon-gamma, interleukin (IL)-1beta, and IL-4, were significantly increased in patients with ITP compared with healthy humans, while MMP8, SLC1A3, CRISP3, THBS1, FMN1, and IL-10 were decreased. In conclusion, the gene expression profile of patients with ITP has established a foundation to study the gene mechanism of ITP progression. PMID- 27554457 TI - Cellular Phenotypic Analysis of Macrophage Activation Unveils Kinetic Responses of Agents Targeting Phosphorylation. AB - Macrophages are highly plastic cells, which serve as sentinels of the host immune system due to their ability to recognize and respond to microbial products rapidly and dynamically. Appropriate regulation of macrophage activation is essential for pathogen clearance or preventing autoimmune diseases. However, regularly used endpoint assays for analyzing macrophage functions have the limitations of being static and non-high throughput. In this study, we introduced a real-time and convenient method based on changes in cellular impedance that are detected by microelectronic biosensors. This new method can record the time/dose dependent cell response profiles (TCRPs) of macrophages in real time and generates physiologically relevant data. The TCRPs generated from classically interferon-gamma/lipopolysaccharide-activated macrophages showed considerable consistency with the data generated from standard endpoint assays. We further explored this approach by using it for global screening of a library of protein tyrosine kinase/phosphatase (PTK/PTP) inhibitors to investigate their impact on macrophage activation. Collectively, our findings suggest that the cellular impedance-based assay provides a promising approach for dynamically monitoring macrophage functions in a convenient and high-throughput manner. PMID- 27554458 TI - Laparoscopic vs. open Nissen's fundoplication for gastro-oesophageal reflux disease in children: A meta-analysis. AB - BACKGROUND AND OBJECTIVE: Available evidence showed inconsistent results between laparoscopic Nissen's fundoplication (LNF) and open Nissen's fundoplication (ONF) for children with gastro-oesophageal reflux disease (GERD), so this study aimed to evaluate the efficacy and safety between LNF and ONF. METHODS: Systematic, comprehensive literature searches were conducted to include randomized controlled trials (RCTs) that compared LNF and ONF for GERD. Two reviewers independently selected studies, abstracted data and assessed the methodological quality and evidence level. Data was analyzed by Review Manager Version 5.0. Risk ratio (RR) was used for dichotomous outcomes, and mean difference (MD) was used for continuous scales. Heterogeneity was estimated with the I2 statistic, fixed effect model was used if I2 <50%, and otherwise random-effects model was used. RESULTS: Three RCTs (171 children) were included. There was not a statistical difference in mortality (RR 1.12, 95%CI 0.50 2.48), or postoperative complications (RR 0.87, 95%CI 0.61 1.25), readmission (RR 1.53, 95%CI 0.67 3.51), or hospital stay (MD 0.85, 95%CI -0.06 1.75) between LNF and ONF. But LNF was associated with more incidence of recurrence (RR 3.32, 95%CI 1.40 7.84), longer surgery duration (MD 76.33, 95%CI 69.37 83.28), but fewer retching (RR 0.11, 95%CI 0.02 0.58) than ONF. CONCLUSIONS: LNF might be as effective and safe as ONF in the short and long term, but both were associated with high risk of recurrence and mortality, especially for those children with neurological impairment, before the age of 18 months and female gender. This required a comprehensive evaluation of children before surgery. PMID- 27554459 TI - Quantitative measurement of mean inner potential and specimen thickness from high resolution off-axis electron holograms of ultra-thin layered WSe2. AB - The phase and amplitude of the electron wavefunction that has passed through ultra-thin flakes of WSe2 is measured from high-resolution off-axis electron holograms. Both the experimental measurements and corresponding computer simulations are used to show that, as a result of dynamical diffraction, the spatially averaged phase does not increase linearly with specimen thickness close to an [001] zone axis orientation even when the specimen has a thickness of only a few layers. It is then not possible to infer the local specimen thickness of the WSe2 from either the phase or the amplitude alone. Instead, we show that the combined analysis of phase and amplitude from experimental measurements and simulations allows an accurate determination of the local specimen thickness. The relationship between phase and projected potential is shown to be approximately linear for extremely thin specimens that are tilted by several degrees in certain directions from the [001] zone axis. A knowledge of the specimen thickness then allows the electrostatic potential to be determined from the measured phase. By using this combined approach, we determine a value for the mean inner potential of WSe2 of 18.9+/-0.8V, which is 12% lower than the value calculated from neutral atom scattering factors. PMID- 27554460 TI - [Management of arterial hypertension before 20weeks gestation in pregnant women]. AB - In the first 6 months of pregnancy, the primary goal of antihypertensive treatment is to prevent the complications of severe hypertension. Initiation of antihypertensive drug treatment is recommended in pregnant women with severe hypertension (blood pressure>160/110mmHg). Initiation of antihypertensive drug treatment should also be considered in pregnant women at high cardiovascular risk (diabetes, chronic kidney disease, personal history of cardiovascular disease) with moderate hypertension (blood pressure between 140-159/90-109mmHg). A systolic blood pressure goal<160 and a diastolic blood pressure goal between 85 and 100mmHg is recommended in pregnancy. Labetalol, nifedipine, nicardipine and alphamethyldopa should be considered preferential antihypertensive drugs in pregnancy. Salt restriction, physical exercise and weight loss have not demonstrated any effect in the prevention of preeclampsia and serious maternal complications of hypertension. PMID- 27554461 TI - [Why and how to treat psychosis earlier?] AB - Chronic psychosis, as for instance schizophrenia, usually begins in young adulthood and may cause severe disability. It causes a mean loss of life expectancy of 22 years. Actual models of psychosis do not trace the beginning of psychosis to the first franc psychotic episode only, but to earlier symptoms. In a classical health system only considering the first psychotic episode, the mean duration of untreated illness (DUI) can last several years. Yet this DUI has a direct impact on the prognosis of the disease. Actual international recommendations prescribe to early detect and treat at risk mental states of psychosis, thus reducing DUI. Such an attitude also helps the patient to integrate care in a moment where she/he is fully in condition to consent and to adhere. Generalist practitioners are crucial actors of early detection. We describe here simple and standardized tools helping early detection of high-risk mental states of psychosis in primary care and the appropriate attitude to do it properly. Numerous countries have developed early detection and treatment centers for psychosis. It has been established that such interventions clearly decrease the risk of transition towards chronic psychosis and improve the prognosis. These recent data about early detection and intervention in psychosis are a major step forward in psychiatry practice. It is now necessary to largely develop such actions in France. PMID- 27554462 TI - [Place of doctors and medicine in our society. What the names given to hospitals reveal]. PMID- 27554463 TI - Site-specific treatment outcome in smokers following 12 months of supportive periodontal therapy. AB - AIM: To evaluate the effect of cigarette smoking on periodontal health at patient, tooth, and site levels following supportive therapy. MATERIALS AND METHODS: Eighty chronic periodontitis patients, 40 smokers and 40 non-smokers, were recruited to a single-arm clinical trial. Periodontal examinations were performed at baseline (T0), 3 months following active periodontal therapy (T1), and 12 months following supportive periodontal therapy (T2). Smoking status was validated measuring serum cotinine levels. Probing depth (PD) >= 5 mm with bleeding on probing (BoP) was defined as the primary outcome. Logistic regression analyses adjusted for clustered observations of patients, teeth, and sites and mixed effects models were employed to analyse the data. RESULTS: All clinical parameters improved from T0 to T2 (p < 0.001), whereas PD, bleeding index (BI), and plaque index (PI) increased from T1 to T2 in smokers and non-smokers (p < 0.001). An overall negative effect of smoking was revealed at T2 (OR = 2.78, CI: 1.49, 5.18, p < 0.001), with the most pronounced effect at maxillary single rooted teeth (OR = 5.08, CI: 2.01, 12.78, p < 0.001). At the patient level, less variation in treatment outcome was detected within smokers (ICC = 0.137) compared with non-smokers (ICC = 0.051). CONCLUSION: Smoking has a negative effect on periodontal health following 12 months of supportive therapy, in particular at maxillary single-rooted teeth. PMID- 27554464 TI - Specialized issue: Lumbar spinal stenosis. PMID- 27554465 TI - Extracorporeal shock wave therapy, ultrasound-guided percutaneous lavage, corticosteroid injection and combined treatment for the treatment of rotator cuff calcific tendinopathy: a network meta-analysis of RCTs. AB - Treatment of calcific tendinitis using extracorporeal shock wave therapy (ESWT), ultrasound-guided percutaneous lavage (UGPL or barbotage), subacromial corticosteroid injection (SAI) and combined treatment is still controversial. This systematic review and meta-regression aimed to compare clinical outcomes between treatments. Relevant RCTs were identified using PubMed and Scopus search engines to date of September 23, 2015. Seven of 920 studies identified were eligible. Compared to the other treatments, the results of this study indicate that ESWT significantly improved CMS and VAS when compared to placebo. Barbotage plus ESWT significantly improved CMS, VAS and decreased size of calcium deposit when compared to ESWT, while barbotage plus SAI significantly improved CMS and decreased size of calcium deposit when compared to SAI. There have no different adverse effects of all treatment groups. Multiple active treatment comparisons indicated that barbotage plus SAI significantly improved VAS and size of calcium deposit when compared to other groups, while barbotage plus SAI improved CMS when compared to other groups. But there was no significant difference. The network meta-analysis suggested that combined US-guided needling and subacromial corticosteroid injection significantly decreased shoulder pain VAS, improved CMS score and decreased the size of calcium deposits, while also lowering risks of adverse event when compared to barbotage plus ESWT, ESWT and subacromial corticosteroid injection; therefore, the evidence points to UGPL as being the treatment of choice for nonsurgical options of treatment in calcific tendinitis of the shoulder. Level of evidence I. PMID- 27554466 TI - [The health professional to the world of Big Data]. PMID- 27554468 TI - White Adipocyte Adiponectin Exocytosis Is Stimulated via beta3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes. AB - We investigated the physiological regulation of adiponectin exocytosis in health and metabolic disease by a combination of membrane capacitance patch-clamp recordings and biochemical measurements of short-term (30-min incubations) adiponectin secretion. Epinephrine or the beta3-adrenergic receptor (AR) agonist CL 316,243 (CL) stimulated adiponectin exocytosis/secretion in cultured 3T3-L1 and in primary subcutaneous mouse adipocytes, and the stimulation was inhibited by the Epac (Exchange Protein directly Activated by cAMP) antagonist ESI-09. The beta3AR was highly expressed in cultured and primary adipocytes, whereas other ARs were detected at lower levels. 3T3-L1 and primary adipocytes expressed Epac1, whereas Epac2 was undetectable. Adiponectin secretion could not be stimulated by epinephrine or CL in adipocytes isolated from obese/type 2 diabetic mice, whereas the basal (unstimulated) adiponectin release level was elevated twofold. Gene expression of beta3AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective ~35% and ~30% reduction at the protein level. Small interfering RNA-mediated knockdown of beta3AR (~60%) and Epac1 (~50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving beta3ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity/type 2 diabetes as a result of the reduced expression of beta3ARs and Epac1 in a state we define as "catecholamine resistance." PMID- 27554467 TI - F1F0 ATP Synthase-Cyclophilin D Interaction Contributes to Diabetes-Induced Synaptic Dysfunction and Cognitive Decline. AB - Mitochondrial abnormalities are well known to cause cognitive decline. However, the underlying molecular basis of mitochondria-associated neuronal and synaptic dysfunction in the diabetic brain remains unclear. Here, using a mitochondrial single-channel patch clamp and cyclophilin D (CypD)-deficient mice (Ppif -/-) with streptozotocin-induced diabetes, we observed an increase in the probability of Ca2+-induced mitochondrial permeability transition pore (mPTP) opening in brain mitochondria of diabetic mice, which was further confirmed by mitochondrial swelling and cytochrome c release induced by Ca2+ overload. Diabetes-induced elevation of CypD triggers enhancement of F1F0 ATP synthase-CypD interaction, which in turn leads to mPTP opening. Indeed, in patients with diabetes, brain cypD protein levels were increased. Notably, blockade of the F1F0 ATP synthase CypD interaction by CypD ablation protected against diabetes-induced mPTP opening, ATP synthesis deficits, oxidative stress, and mitochondria dysfunction. Furthermore, the absence of CypD alleviated deficits in synaptic plasticity, learning, and memory in diabetic mice. Thus, blockade of ATP synthase interaction with CypD provides a promising new target for therapeutic intervention in diabetic encephalopathy. PMID- 27554469 TI - FGF21 Improves the Adipocyte Dysfunction Related to Seipin Deficiency. AB - Fibroblast growth factor 21 (FGF21) was shown to improve metabolic homeostasis, at least partly by controlling white adipocyte profile and adiponectin secretion. Here, we studied its effect on adipocyte dysfunction in the context of Berardinelli-Seip congenital lipodystrophy (BSCL) linked to seipin deficiency. Bscl2-/- mice displayed a progressive adipose tissue loss with aging as evidenced by the altered profile of residual fat pads and the decrease in adiponectin plasma levels in 12- vs. 4-week-old animals. Aiming to prevent this impairment, we treated 6-week-old Bscl2-/- mice with an FGF21 analog (LY2405319) for a period of 28 days. FGF21 treatment increased adiponectin plasma levels and normalized insulin sensitivity in Bscl2-/- mice by improving the white adipose tissue gene expression pattern. To further decipher the molecular pathways altered by seipin deficiency in mature adipocytes, we developed a unique inducible seipin knockdown cell line (SKD). SKD showed chronic activation of the p38 MAPK pathway associated with apoptotic cell death. Interestingly, FGF21 treatment exerted an antistress effect on SKD cells, reducing p38 MAPK phosphorylation and limiting mature adipocyte loss. Our data demonstrate that FGF21 treatment improves the metabolic profile of Bscl2-/- lipodystrophic mice, partly by improving mature adipocyte maintenance through suppression of cellular stress via inhibition of p38 MAPK activity. PMID- 27554470 TI - Adipose-Specific Deficiency of Fumarate Hydratase in Mice Protects Against Obesity, Hepatic Steatosis, and Insulin Resistance. AB - Obesity and type 2 diabetes are associated with impaired mitochondrial function in adipose tissue. To study the effects of primary deficiency of mitochondrial energy metabolism in fat, we generated mice with adipose-specific deficiency of fumarate hydratase (FH), an integral Krebs cycle enzyme (AFHKO mice). AFHKO mice have severe ultrastructural abnormalities of mitochondria, ATP depletion in white adipose tissue (WAT) and brown adipose tissue, low WAT mass with small adipocytes, and impaired thermogenesis with large unilocular brown adipocytes. AFHKO mice are strongly protected against obesity, insulin resistance, and fatty liver despite aging and high-fat feeding. AFHKO white adipocytes showed normal lipolysis but low triglyceride synthesis. ATP depletion in normal white adipocytes by mitochondrial toxins also decreased triglyceride synthesis, proportionally to ATP depletion, suggesting that reduced triglyceride synthesis may result nonspecifically from adipocyte energy deficiency. At thermoneutrality, protection from insulin resistance and hepatic steatosis was diminished. Taken together, the results show that under the cold stress of regular animal room conditions, adipocyte-specific FH deficiency in mice causes mitochondrial energy depletion in adipose tissues and protects from obesity, hepatic steatosis, and insulin resistance, suggesting that in cold-stressed animals, mitochondrial function in adipose tissue is a determinant of fat mass and insulin sensitivity. PMID- 27554471 TI - Salsalate (Salicylate) Uncouples Mitochondria, Improves Glucose Homeostasis, and Reduces Liver Lipids Independent of AMPK-beta1. AB - Salsalate is a prodrug of salicylate that lowers blood glucose in patients with type 2 diabetes (T2D) and reduces nonalcoholic fatty liver disease (NAFLD) in animal models; however, the mechanism mediating these effects is unclear. Salicylate directly activates AMPK via the beta1 subunit, but whether salsalate requires AMPK-beta1 to improve T2D and NAFLD has not been examined. Therefore, wild-type (WT) and AMPK-beta1-knockout (AMPK-beta1KO) mice were treated with a salsalate dose resulting in clinically relevant serum salicylate concentrations (~1 mmol/L). Salsalate treatment increased VO2, lowered fasting glucose, improved glucose tolerance, and led to an ~55% reduction in liver lipid content. These effects were observed in both WT and AMPK-beta1KO mice. To explain these AMPK independent effects, we found that salicylate increases oligomycin-insensitive respiration (state 4o) and directly increases mitochondrial proton conductance at clinical concentrations. This uncoupling effect is tightly correlated with the suppression of de novo lipogenesis. Salicylate is also able to stimulate brown adipose tissue respiration independent of uncoupling protein 1. These data indicate that the primary mechanism by which salsalate improves glucose homeostasis and NAFLD is via salicylate-driven mitochondrial uncoupling. PMID- 27554472 TI - Deficiency in the Heat Stress Response Could Underlie Susceptibility to Metabolic Disease. AB - Heat treatment (HT) effectively prevents insulin resistance and glucose intolerance in rats fed a high-fat diet (HFD). The positive metabolic actions of heat shock protein 72 (HSP72), which include increased oxidative capacity and enhanced mitochondrial function, underlie the protective effects of HT. The purpose of this study was to test the ability of HSP72 induction to mitigate the effects of consumption of a short-term 3-day HFD in rats selectively bred to be low-capacity runners (LCRs) and high-capacity runners (HCRs)-selective breeding that results in disparate differences in intrinsic aerobic capacity. HCR and LCR rats were fed a chow or HFD for 3 days and received a single in vivo HT (41 degrees C, for 20 min) or sham treatment (ST). Blood, skeletal muscles, liver, and adipose tissues were harvested 24 h after HT/ST. HT decreased blood glucose levels, adipocyte size, and triglyceride accumulation in liver and muscle and restored insulin sensitivity in glycolytic muscles from LCR rats. As expected, HCR rats were protected from the HFD. Importantly, HSP72 induction was decreased in LCR rats after only 3 days of eating the HFD. Deficiency in the highly conserved stress response mediated by HSPs could underlie susceptibility to metabolic disease with low aerobic capacity. PMID- 27554473 TI - Loss of Mbd2 Protects Mice Against High-Fat Diet-Induced Obesity and Insulin Resistance by Regulating the Homeostasis of Energy Storage and Expenditure. AB - Previous studies including ours demonstrated that methyl-CpG-binding domain 2 (MBD2) acts as a reader to decipher DNA methylome-encoded information. We thus in the current study used Mbd2-/- mice as a model to dissect the impact of high-fat diet (HFD) on DNA methylome relevant to the pathoetiology of obesity. It was interestingly noted that mice deficient in Mbd2 were protected from HFD-induced obesity and insulin resistance. Mechanistic study revealed that HFD rendered epididymal adipose tissues to undergo a DNA methylation turnover as evidenced by the changes of methylation levels and patterns. Specifically, HFD was noted with higher potency to induce DNA hypomethylation in genes relevant to energy storage than that in genes associated with energy expenditure. As a result, arrays of genes were subjected to expression changes, which led to an altered homeostasis for energy storage and expenditure in favor of obesity development. Loss of Mbd2 resulted in impaired implementation of above DNA methylation changes associated with altered energy homeostasis, which then protected mice from HFD-induced obesity and insulin resistance. Those data would provide novel insight into the understanding of the pathoetiology underlying obesity with potential for developing effective therapies against obesity in clinical settings. PMID- 27554474 TI - Systematic Functional Characterization of Candidate Causal Genes for Type 2 Diabetes Risk Variants. AB - Most genetic association signals for type 2 diabetes risk are located in noncoding regions of the genome, hindering translation into molecular mechanisms. Physiological studies have shown a majority of disease-associated variants to exert their effects through pancreatic islet dysfunction. Systematically characterizing the role of regional transcripts in beta-cell function could identify the underlying disease-causing genes, but large-scale studies in human cellular models have previously been impractical. We developed a robust and scalable strategy based on arrayed gene silencing in the human beta-cell line EndoC-betaH1. In a screen of 300 positional candidates selected from 75 type 2 diabetes regions, each gene was assayed for effects on multiple disease-relevant phenotypes, including insulin secretion and cellular proliferation. We identified a total of 45 genes involved in beta-cell function, pointing to possible causal mechanisms at 37 disease-associated loci. The results showed a strong enrichment for genes implicated in monogenic diabetes. Selected effects were validated in a follow-up study, including several genes (ARL15, ZMIZ1, and THADA) with previously unknown or poorly described roles in beta-cell biology. We have demonstrated the feasibility of systematic functional screening in a human beta cell model and successfully prioritized plausible disease-causing genes at more than half of the regions investigated. PMID- 27554475 TI - The Inactivation of RabGAP Function of AS160 Promotes Lysosomal Degradation of GLUT4 and Causes Postprandial Hyperglycemia and Hyperinsulinemia. AB - The AS160 (Akt substrate of 160 kDa) is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers GLUT4 protein levels and causes severe insulin resistance. How its deficiency causes diminished GLUT4 proteins remains unknown. We found that the deletion of AS160 decreased GLUT4 levels in a cell/tissue-autonomous manner. Consequently, skeletal muscle-specific deletion of AS160 caused postprandial hyperglycemia and hyperinsulinemia. The pathogenic effects of AS160 deletion are mainly, if not exclusively, due to the loss of its RabGAP function since the RabGAP-inactive AS160R917K mutant mice phenocopied the AS160 knockout mice. The inactivation of RabGAP of AS160 promotes lysosomal degradation of GLUT4, and the inhibition of lysosome function could restore GLUT4 protein levels. Collectively, these findings demonstrate that the RabGAP activity of AS160 maintains GLUT4 protein levels in a cell/tissue-autonomous manner and its inactivation causes lysosomal degradation of GLUT4 and postprandial hyperglycemia and hyperinsulinemia. PMID- 27554476 TI - Oxytocin Improves beta-Cell Responsivity and Glucose Tolerance in Healthy Men. AB - In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in beta-cell responsivity (PHItotal) that was largely due to an enhanced dynamic response (PHId), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment. PMID- 27554477 TI - Nationwide Population-Based Incidence and Survival Rates of Malignant Central Nervous System Germ Cell Tumors in Korea, 2005-2012. AB - PURPOSE: Malignant central nervous system (CNS) germ cell tumors (GCTs), although rare, are thought to occur more frequently among Asians. However, a recent population-based study revealed no differences in GCT incidence between Asians and Caucasians. Therefore, this study was conducted to determine the incidence and survival rates of CNS GCTs using the national cancer incidence database, and to compare these rates to those in the United States and Japan. MATERIALS AND METHODS: We extracted CNS GCT patients diagnosed between 2005 and 2012 from the Korea Central Cancer Registry database. Age-standardized rates (ASRs), annual percentage change, and the male-female incidence rate ratios (IRRs) were calculated. To estimate the survival rate, we used data for patients diagnosed between 2005 and 2010 and followed their cases until December 31, 2013. RESULTS: The ASR for CNS GCT between 2005 and 2012 was 0.179 per 100,000 (95% confidence interval, 0.166 to 0.193), with an overall male-to-female (M:F) IRR of 2.95:1. However, when stratified by site, the M:F IRR was 13.62:1 for tumors of the pineal region and 1.87:1 for those located in nonpineal regions. The most frequent histologic type was germinoma (76.0%), and the most frequent location was the suprasellar region (48.5%). The 5-year survival rate of germinoma patients was 95.3%. CONCLUSION: The incidence rate of CNS GCTs in Korea during 2005-2012 was 0.179 per 100,000, which was similar to that of the Asian/Pacific Islander subpopulation in the United States. Moreover, the CNS GCT survival rate in Korea was similar to rates in Japan and the United States. PMID- 27554478 TI - Magnetic Resonance Imaging-Detected Intracranial Extension in the T4 Classification Nasopharyngeal Carcinoma with Intensity-Modulated Radiotherapy. AB - PURPOSE: This study was conducted is to identify the prognostic value and staging categories of magnetic resonance imaging (MRI)-detected intracranial extension in nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT) to determine whether it is necessary to subclassify the T4 classification NPC. MATERIALS AND METHODS: A total of 335 nonmetastatic T4 classification NPC patients with MRI treated between March 2004 and June 2011 by radical IMRT were included. The T4 classification patients were subclassified into two grades (T4a, without intracranial extension vs. T4b, with intracranial extension) according to the site of invasion. RESULTS: The frequency of intracranial extension was 40.9% (137 of 335 patients). Multivariate analysis identified subclassification (T4a vs. T4b) as an independent prognostic factor for local failure-free survival (p=0.049; hazard ratio [HR], 0.498) and overall survival (p=0.004; HR, 0.572); however, it had no effect on regional failure-free survival or distant failure free survival (p > 0.050). CONCLUSION: For patients with T4 classification NPC, those with MRI-detected intracranial extension are more likely to experience local failure and death after IMRT than patients without intracranial extension. According to the site of invasion, subclassification of T4 patients as T4a or T4b has prognostic value in NPC. PMID- 27554479 TI - Young Age Is Associated with Increased Locoregional Recurrence in Node-Positive Breast Cancer with Luminal Subtypes. AB - PURPOSE: The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes. MATERIALS AND METHODS: Medical records of 524 breast cancer patients with positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapy was administered to 413 patients with positive hormone receptors according to their menstrual status. RESULTS: During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those >= 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for >= 40 years; p < 0.01). Multivariate analysis using luminal subtypes >= 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01). CONCLUSION: Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged >= 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes. PMID- 27554480 TI - Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution. AB - PURPOSE: This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors. MATERIALS AND METHODS: A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months). RESULTS: The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%). CONCLUSION: Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches. PMID- 27554481 TI - DNA Methyltransferase Gene Polymorphisms for Prediction of Radiation-Induced Skin Fibrosis after Treatment of Breast Cancer: A Multifactorial Genetic Approach. AB - PURPOSE: This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation induced fibrosis. MATERIALS AND METHODS: DNMT1 rs2228611,DNMT3A rs1550117,DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC). RESULTS: Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade >= 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation-induced fibrosis (GG vs. AA; hazard ratio, 0.26; 95% confidence interval [CI], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611 to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% CI, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710). CONCLUSION: DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models. PMID- 27554482 TI - Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer in Korea. AB - PURPOSE: Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. MATERIALS AND METHODS: This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. RESULTS: The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval <= 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. CONCLUSION: Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC. PMID- 27554483 TI - Systematic Review of Clinical Practice Guidelines for Failed Antidepressant Treatment Response in Major Depressive Disorder, Dysthymia, and Subthreshold Depression in Adults. AB - OBJECTIVE: This systematic review critically evaluated clinical practice guidelines (CPGs) for treating adults with major depressive disorder, dysthymia, or subthreshold or minor depression for recommendations following inadequate response to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). METHOD: Searches for CPGs (January 2004 to November 2014) in English included 7 bibliographic databases and grey literature sources using CPG and depression as the keywords. Two raters selected CPGs on depression with a national scope. Data extraction included definitions of adequate response and recommended treatment options. Two raters assessed quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: From 46,908 citations, 3167 were screened at full text. From these 21 CPG were applicable to adults in primary care and outpatient settings. Five CPGs consider patients with dysthymia or subthreshold or minor depression. None provides recommendations for those who do not respond to first-line SSRI treatment. For adults with MDD, most CPGs do not define an "inadequate response" or provide specific suggestions regarding how to choose alternative medications when switching to an alternative antidepressant. There is variability between CPGs in recommending combination strategies. AGREE II ratings for stakeholder involvement in CPG development, editorial independence, and rigor of development are domains in which depression guidelines are often less robust. CONCLUSIONS: About half of patients with depression require second-line treatment to achieve remission. Consistency and clarity in guidelines for second-line treatment of depression are therefore important for clinicians but lacking in most current guidelines. This may reflect a paucity of primary studies upon which to base conclusions. PMID- 27554484 TI - Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability. AB - The TIM22 complex mediates the import of hydrophobic carrier proteins into the mitochondrial inner membrane. While the TIM22 machinery has been well characterised in yeast, the human complex remains poorly characterised. Here, we identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it's C-terminus exposed to the intermembrane space. Tim29 is required for the stability of the TIM22 complex and functions in the assembly of hTim22. Furthermore, Tim29 contacts the Translocase of the Outer Mitochondrial Membrane, TOM complex, enabling a mechanism for transport of hydrophobic carrier substrates across the aqueous intermembrane space. Identification of Tim29 highlights the significance of analysing mitochondrial import systems across phylogenetic boundaries, which can reveal novel components and mechanisms in higher organisms. PMID- 27554487 TI - [Total temporomandibular joint prostheses]. AB - The temporomandibular joint (TMJ) is probably the most complex human joint. As in all joints, its prosthetic replacement may be indicated in selected cases. Significant advances have been made in the design of TMJ prostheses during the last three decades and the indications have been clarified. The aim of our work was to make an update on the current total TMJ total joint replacement. Indications, contraindications, prosthetic components, advantages, disadvantages, reasons for failure or reoperation, virtual planning and surgical protocol have been exposed. PMID- 27554486 TI - Hunger neurons drive feeding through a sustained, positive reinforcement signal. AB - The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states. PMID- 27554485 TI - Muscle contraction is required to maintain the pool of muscle progenitors via YAP and NOTCH during fetal myogenesis. AB - The importance of mechanical activity in the regulation of muscle progenitors during chick development has not been investigated. We show that immobilization decreases NOTCH activity and mimics a NOTCH loss-of-function phenotype, a reduction in the number of muscle progenitors and increased differentiation. Ligand-induced NOTCH activation prevents the reduction of muscle progenitors and the increase of differentiation upon immobilization. Inhibition of NOTCH ligand activity in muscle fibers suffices to reduce the progenitor pool. Furthermore, immobilization reduces the activity of the transcriptional co-activator YAP and the expression of the NOTCH ligand JAG2 in muscle fibers. YAP forced-activity in muscle fibers prevents the decrease of JAG2 expression and the number of PAX7+ cells in immobilization conditions. Our results identify a novel mechanism acting downstream of muscle contraction, where YAP activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH in a non-cell-autonomous manner. PMID- 27554488 TI - [Arthrocentesis of the temporomandibular joint and intra-articular injections : An update]. AB - INTRODUCTION: Arthocentesis of the temporomandibular joint combined with intra articular washout and, more recently, intra-articular injection of pharmacological agents has been developed from the 1990s and is nowadays extensively in use for the treatment of temporomandibular dysfunctions (TMDs). The goal of our work was to answer 3 questions: 1. Is intra-articular washout effective for the treatment of TMDs ? 2. What kind of pharmacological agents may nowadays be injected in addition to washout and are these injections useful ? 3. What is the place of these treatments in the treatment strategies of TMDs ? MATERIAL AND METHODS: A bibliographic research has been carried out in the PubMed database using following keywords arthrocentesis, temporomandibular joint. The 27 articles published between 1991 and 2016, indicating patient's inclusion criterions and objectively evaluating the clinical results (mouth opening, intra articular noises, pain) were selected. Pharmacological agents were noticed when used. RESULTS: 1. All authors concluded to the efficacy of intra-articular washout. No prognostic factor for arthrocentesis efficacy could be identified. 2. Main pharmacological agents used were steroids, hyaluronic acid, morphine-based drugs and platelet rich plasma. Superiority of ith-injection protocols failed to win unanimous support. All authors who compared with- and without-injection protocols concluded to the superiority of with-injection protocols, whatever the agent. DISCUSSION: Numerous studies have proven the efficacy of intra-articular washout for the treatment of TMDs resistant to noninvasive treatments. The advantage of any kind of pharmacological agent is not clear. Mechanisms of action are not all elucidated. No pharmacological agent showed any superiority over another. Study methodologies are often defective: imprecise inclusion criterions, short follow-up, confounding variables not taken into account, few comparison between pharmacological agents. PMID- 27554489 TI - [Congenital malformations of the temporo-mandibular joint and the mandibular ramus: Grafting vs distraction osteogenesis]. AB - Congenital deformities of the mandibular ramus and of the temporo-mandibular joint are treated by surgery since the early 20th century. However, morphological and functional results are often disappointing, accounting for iterative operations. Today, a clear consensus concerning the type of intervention to be proposed, and at what age it should be carried out does not yet exist. For mild cases, "conventional" orthognathic or osteogenic distraction procedures seem to work well, especially if they are carried out at the end of growth. In severe cases, it is often necessary to proceed in several surgical steps, usually starting with a chondrocostal graft, especially when interceptive surgery, performed before the end of growth, is preferred in order to improve the patient's quality of life. PMID- 27554490 TI - [Temporomandibular joint arthropathy in situ steroid injection]. AB - INTRODUCTION: Temporomandibular disorders (TMDs) affect the masticatory muscles and the temporomandibular joints (TMJs). TMDs most often result from occlusal and/or muscular disorders and are then called primary or idiopathic TMDs. Less frequently, TMDs are related to local (trauma, infection) or general (rheumatoid arthritis) causes and are then called secondary TMDs. A little known iatrogenic cause of secondary TDM is the osteoarthritis that may be induced by intra articular cortisone injections. We report one case of condylar lysis that occurred after one single intra-articular cortisone injection. OBSERVATION: A 62 years-old woman consulted for a long-lasting TMD on the left side manifesting itself through pain and noise. She benefited one year before from an intra articular injection of cortisone by her rheumatologist for repeated closed lock of her left TMJ. Physical examination showed limited mouth opening with deviation on the left side. Lateral movements on the right side were impossible. The panoramic X-ray showed a condylar lysis on the left side that was on the CT scan. MRI additionally showed an anteriorly displaced and severely reshaped disc and an articular inflammation without intra-articular effusion. DISCUSSION: TMJ osteoarthritis secondary to unique or repeated intra-articular steroid injections are little-known. They are clinically expressed as typical TMDs and characterized on X-rays by condylar lysis and inflammation. Intra-articular injections of steroids are not totally harmless and other treatments must be preferred. PMID- 27554491 TI - [TMJ, eating and breathing]. AB - The study of the relationship between temporomandibular joints (TMJ), mastication and ventilation and the involvement of these two functions in the genesis of primary Temporomandibular Disorders (TMD) and in some dentofacial deformities, was initiated in France, more than 30years, by Professor Raymond Gola. Once criticized the weakness of the scientific literature in this domain, the originality of the TMJ within the masticatory system is recalled with its huge adaptation potential to very different biomechanical constraints according to the age and masticatory activities during the day. But the biomechanics of the masticatory system does not stop at night and the positions of the mandible and head during sleep should be studied carefully. In case of nocturnal mouth breathing with open mouth, the predominant sleeping position (generating small but long-term strengths) may be deleterious to the condyle-disc complex, to the surrounding muscles and the occlusal relationships. Some condyle-disc displacements and asymmetric malocclusions occur in this long portion of life what sleep, especially as oral breathing leads to a lot of dysfunctions (low position of the tongue, labio-lingual dysfunctions, exacerbation of bruxism sleep...). The aim of this work was to share our multidisciplinary experience of the biomechanical consequences of the nocturnal mouth breathing on the face involving orthodontists, maxillofacial surgeons, ENT, allergists, speech therapists, physiotherapists and radiologists. PMID- 27554492 TI - Marked improvement in the success rate of medical management of early pregnancy failure following the implementation of a novel institutional protocol and treatment guidelines: a follow-up study. AB - PURPOSE: To analyze the success rate, time to passage of tissue and subjective patient experience of a newly implemented protocol for medical management of early pregnancy failure (EPF) over a 2-year period. METHODS: A retrospective chart review of all patients with early pregnancy failure primarily opting for medical management was performed. 200 mg mifepristone were administered orally, followed by a single vaginal dose of 800 mcg misoprostol after 36-48 h. We followed-up with our patients using a written questionnaire. RESULTS: 167 women were included in the present study. We observed an overall success rate of 92 %, defined as no need for surgical management after medication administration. We could not identify predictive values for success in a multivariate regression analysis. Most patients (84 %) passed tissue within 6 h after misoprostol administration. The protocol was well tolerated with a low incidence of side effects. Pain was managed well with sufficient analgesics. Responders to the questionnaire felt adequately informed prior to treatment and rated their overall experience as positive. CONCLUSION: The adaption of the institutional medical protocol resulted in a marked improvement of success rate when compared to the previously used protocol (92 vs. 61 %). We credit this increase to the adjusted medication schema as well as to targeted physician education on the expected course and interpretation of outcome measures. Our results underscore that the medical management of EPF is a safe and effective alternative to surgical evacuation in the clinical setting. PMID- 27554494 TI - Author's Reply to Sani et al.: "Effects of Exercise Training in Hypoxia Versus Normoxia on Vascular Health: Comments on Clinical Importance"-Facing Common Misconceptions Concerning Meta-Analysis in Biomedical Research. PMID- 27554495 TI - Biosynthetic gene clusters for relevant secondary metabolites produced by Penicillium roqueforti in blue cheeses. AB - Ripening of blue-veined cheeses, such as the French Bleu and Roquefort, the Italian Gorgonzola, the English Stilton, the Danish Danablu or the Spanish Cabrales, Picon Bejes-Tresviso, and Valdeon, requires the growth and enzymatic activity of the mold Penicillium roqueforti, which is responsible for the characteristic texture, blue-green spots, and aroma of these types of cheeses. This filamentous fungus is able to synthesize different secondary metabolites, including andrastins, mycophenolic acid, and several mycotoxins, such as roquefortines C and D, PR-toxin and eremofortins, isofumigaclavines A and B, and festuclavine. This review provides a detailed description of the main secondary metabolites produced by P. roqueforti in blue cheese, giving a special emphasis to roquefortine, PR-toxin and mycophenolic acid, and their biosynthetic gene clusters and pathways. The knowledge of these clusters and secondary metabolism pathways, together with the ability of P. roqueforti to produce beneficial secondary metabolites, is of interest for commercial purposes. PMID- 27554493 TI - Recent advances in the noninvasive strategies of cardiac amyloidosis. AB - The heart, like any organ in the body, is susceptible to amyloid deposition. Although more than 30 types of protein can cause amyloidosis, only two types commonly deposit in the ventricular myocardium: amyloid light chain and amyloid transthyretin. Amyloid cardiomyopathy is usually a major determinant of patient outcomes, and the diagnosis of heart involvement can be often relatively under diagnosed, owing to nonspecific presenting symptoms and signs at a subclinical stage. The diagnosis of cardiac amyloidosis is usually performed by endomyocardial biopsy; however, the invasive nature and related high-risk complications restrict its wide use in clinical settings. Recently, with the advent of innovative techniques used for evaluating cardiac amyloidosis, noninvasive methods become increasingly important, especially in earlier diagnosis, distinguishing typing, risk prediction and response to treatment. Here, we will review recent developments in the noninvasive methods used in the assessment of cardiac amyloidosis, focused on the laboratory biomarkers and imaging modalities. PMID- 27554496 TI - Investigation on antimicrobial agents of the terrestrial Streptomyces sp. BCC71188. AB - The terrestrial actinomycete strain BCC71188 was identified as Streptomyces by its morphology (having spiral chain spore on the aerial mycelium), chemotaxonomy (containing LL-diaminopimelic acid in the cell wall), and 16S rRNA gene sequence analysis [showing high similarity values compared with Streptomyces samsunensis M1463T (99.85 %) and Streptomyces malaysiensis NBRC 16446T (99.40 %)]. The crude extract exhibited antimalarial against Plasmodium falciparum (IC50 0.19 MUg/ml), anti-TB against Mycobacterial tuberculosis (MIC 6.25 MUg/ml), and antibacterial against Bacillus cereus (MIC 1.56 MUg/ml) activities. Therefore, chemical investigation was conducted by employing bioassay-guided method and led to the isolation of 19 compounds including two cyclic peptides (1-2), five macrolides (3 7), new naphthoquinone (8), nahuoic acid C (9), geldanamycin derivatives (10-13), cyclooctatin (14), germicidins A (15) and C (16), actinoramide A (17), abierixin, and 29-O-methylabierixin. These isolated compounds were evaluated for antimicrobial activity, such as antimalarial, anti-TB, and antibacterial activities, and for cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells. Compounds 1-7, 10-14 exhibited antimalarial (IC50 0.22-7.14 MUg/ml), and elaiophylin analogs (4-6) displayed anti-TB (MIC 0.78 12.00 MUg/ml) and B. cereus (MIC 0.78-3.13 MUg/ml) activities. Compounds 1, 2, 14, and abierixin displayed weak cytotoxicity, indicating a potential for antimicrobial agents. PMID- 27554497 TI - L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation. AB - BACKGROUND/AIMS: The interactions between calcium oxalate monohydrate (COM) crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. METHODS: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. RESULTS: Dedifferentiated MDCK cells induced by transforming growth factor beta1 (TGF-beta1) shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3beta/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. CONCLUSIONS: COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3beta/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis. PMID- 27554498 TI - Prevalence of functional gastrointestinal disorders among adolescents in Delhi based on Rome III criteria: A school-based survey. AB - BACKGROUND: Functional gastrointestinal diseases (FGIDs) are emerging as an important cause of morbidity in adolescents globally. The prevalence of FGIDs among Indian children or adolescents is not clear. METHODS: A cross-sectional school-based survey conducted in 1115 children aged 10-17 years attending four semi urban government schools of National capital territory (NCT) of Delhi. Rome III questionnaire was translated into Hindi and was filled by the students under supervision. Prevalence of FGIDs was calculated. RESULTS: Ten percent (112) adolescents had FGIDs. Out of 112, 52 % (58) were boys, and 48 % (54) were girls. 2.7 % (30) had functional dyspepsia, 1.3 % (15) had irritable bowel syndrome, 1.4 % (16) had abdominal migraine, 1.5 % (17) had aerophagia, 0.4 % (5) had functional abdominal pain syndrome, and 0.3 % (4) had functional abdominal pain. Prevalence of functional constipation, adolescent rumination syndrome, cyclical vomiting syndrome, and non-retentive fecal incontinence were 0.5 % (6), 0.3 % (4), 0.3 % (3), 0.4 % (5), respectively. Functional abdominal pain-related FGID were present in 6.3 % (70) children (35 boys and 35 girls). Functional constipation (4 vs. 2) and functional abdominal pain syndrome (4 vs. 1, p < 0.05) were significantly more in females. CONCLUSIONS: The prevalence of functional gastrointestinal disorders in our study was 10 %. The most frequent FGID noted was functional dyspepsia. PMID- 27554499 TI - Extensive analysis of milk fatty acids in two fat-tailed sheep breeds during lactation. AB - The profile of fatty acids (FA) in the milk fat of two Iranian fat-tailed sheep breeds, Sanjabi and Mehraban, was compared during lactation. Eight ewes of each breed, balanced in parity and carrying one foetus, were selected before parturition. Ewes were kept separated in individual pens during the experimental period, under the same management practices and fed the same diet, in order to eliminate any confounding effects on milk FA profile. Milk was sampled at biweekly intervals up to 10 weeks of lactation, starting 2 weeks after parturition. More than 100 FA were determined in milk fat by means of gas chromatography. The milk fat of Sanjabi ewes contained more cis-9 18:1, that of Mehraban ewes was richer in 10:0, 12:0 and 14:0, and no differences were found for 16:0 and 18:0. No breed differences were found for most branched-chain FA. Mehraban ewes showed a higher presence of vaccenic and rumenic acids in their milk fat. The milk fat of Sanjabi ewes had a lower atherogenicity index and n-6/n 3 FA ratio. The contents of several FA showed time-dependent changes, so breed differences were more apparent or disappeared as lactation progressed. The milk fat of Sanjabi ewes showed a better FA profile from the human health point of view. PMID- 27554500 TI - Toxoplasmosis in camels (Camelus dromedarius) of Borana zone, Oromia region, Ethiopia: seroprevalence and risk factors. AB - Toxoplasmosis is one of the most prevalent parasitic infections of medical and veterinary importance. A cross-sectional study was conducted from November 2013 to January 2014 to estimate the seroprevalence of Toxoplasma gondii infection in camels from four districts of Borana zone, Southern Oromia, Ethiopia. In addition, a questionnaire survey was administered to 124 pastoralists to identify possible risk factors and to assess the awareness level of pastoral communities about toxoplasmosis. A total of 396 serum samples were examined for anti Toxoplasma IgG antibodies using the direct agglutination test (DAT). Fisher's exact test and logistic regression were used for data analysis. An overall seroprevalence of 8.33 % (95 % confidence interval [CI] 5.60 %, 11.07 %) at animal-level and 37.5 % (95 % CI: 20.1 %, 57.4 %) at herd-level was found. The seroprevalence was significantly high in Moyale district (23.07 %) followed by Yabello (7.20 %), Dirre (3.77 %), and Arero (0.0 %) districts (P < 0.001). Multivariable logistic regression analysis revealed that the likelihood of acquiring T. gondii infection was significantly higher in camels of Moyale district (adjusted OR = 5.89, 95 % CI 2.15, 16.12; P = 0.001) than Dirre district, in camels of >8 years old (adjusted odds ratio [OR] = 4.95, 95 % CI 1.68, 14.55; P = 0.004) than camels of <=4 years old. There was no significant association between herd-level seroprevalence of T. gondii infection and abortion history, herd size, and presence of domestic cats and wild felids (P > 0.05). The majority of interviewees were uneducated (82.25 %), and all had no knowledge of toxoplasmosis. All camel herders drink raw camel milk but consume cooked meat (90.32 %). Of the interviewees, 93.06 % are aware about soil-eating habit of camels and provide salt supplement for their camels. Majority of the respondents practice improper disposal of aborted materials (throw along the way) (88.70 %), and 73 % of the study participants do not wash their hands after handling aborted fetus. The results of the present study confirm relatively lower prevalence of T. gondii infection in camels reared in Borana zone. Age and study district are significant predictors of T. gondii seropositivity. The vast majorities of interviewed pastoralists were uneducated and practice poor biosecurity measures to prevent diseases. Education of pastoralists about biosecurity measures to prevent toxoplasmosis and further studies are warranted to unravel the economic and public health consequences of T. gondii infection. PMID- 27554501 TI - Impact of Portal Vein Involvement from Pancreatic Cancer on Metastatic Pattern After Surgical Resection. AB - BACKGROUND: The present study aims to evaluate the long-term outcome and metastatic pattern of patients who underwent resection of a pancreatic ductal adenocarcinoma (PDAC) with portal or superior mesenteric vein (PV/SMV) resection. METHODS: Patients who underwent a partial pancreatoduodenectomy or total pancreatectomy for PDAC between 2005 and 2015 were retrospectively analyzed. Three subgroups were generated, depending on PV/SMV resection (P+) and pathohistological PV/SMV tumor infiltration (I+): P+I+, P+I-, and P-I-. Statistical analysis was performed using the R software package. RESULTS: The study cohort included 179 patients, 113 of whom underwent simultaneous PV/SMV resection. Thirty-six patients (31.9 %) had pathohistological tumor infiltration of the PV/SMV (P+I+), and were matched with 66 cases without PV/SMV infiltration (P-I-). The study revealed differences in overall median survival (11.9 [P+I+] vs. 16.1 [P+I-] vs. 20.1 [P-I-] months; p = 0.01). Multivariate survival analysis identified true invasion of the PV/SMV as the only significant, negative prognostic factor (p = 0.01). Whereas the incidence of local recurrence was comparable (p = 0.96), the proportion of patients with distant metastasis showed significant differences (75 % [P+I+] vs. 45.8 % [P+I-] vs. 54.7 % [P-I-], p = 0.01). Furthermore, the median time to progression was significantly shorter if the PV/SMV was involved (7.4 months [P+I+] vs. 10.9 months [P+I-] vs. 11.6 months [P-I-]). Initial liver metastases occurred in 33 % of the patients. CONCLUSIONS: True invasion of the PV/SMV is an independent risk factor for overall survival, and is associated with a higher incidence of distant metastasis and shorter progressive-free survival. Radical vascular resection cannot compensate for aggressive tumor biology. PMID- 27554502 TI - Results of Resection for Recurrent or Residual Retroperitoneal Sarcoma After Failed Primary Treatment. AB - BACKGROUND: Local recurrence after resection of retroperitoneal sarcoma (RPS) is a common and difficult problem. Gross residual disease after incomplete resection is a particular challenge. The authors reviewed their experience with patients referred for management of recurrent or residual RPS. METHODS: Patients seen at the authors' center from 1996 to 2013 who had undergone resection at an outside institution were identified from a prospective database. Kaplan-Meier survival curves were generated and compared by log-rank analysis. RESULTS: A total of 45 patients were referred with recurrent (n = 33) or residual (n = 12) disease. Before initial surgery elsewhere, cross-sectional imaging (computed tomograpy/magnetic resonance imaging) had been obtained for 30 patients (67 %) and percutaneous biopsy for 8 patients (18 %). At referral to the authors' center, 15 patients were deemed inappropriate for resection, with a subsequent median overall survival (OS) period of 15 months. At the authors' center, 30 patients (22 with recurrent and 8 with residual disease) were resected. The majority received preoperative radiation (77 %). The postoperative mortality rate was 0 % in the recurrent group and 25 % (2/8) in the residual group (p = 0.015). Among the 30 resected patients, the median and 5-year OS was 53 months (50 %), and the OS was better in the recurrent group (median, 77 months) than in the residual group (median, 41 months (p = 0.027). The median time to local re recurrence was 49 months in the recurrent group and 35 months in the residual group (p = 0.730). CONCLUSIONS: Durable disease control and prolonged survival may be achieved for selected patients with recurrent RPS. In this study, resection after previous grossly incomplete resection was associated with high postoperative mortality and inferior OS. The benefit of extensive surgery for these patients may be limited. PMID- 27554503 TI - Maybe you should blame your parents: Parental attachment, gender, and problematic Internet use. AB - Background and aims Prior research has generally established parental attachment as a predictor of problematic Internet use (PIU). However, findings across studies are inconsistent as to which factor(s) of attachment style (i.e., attachment anxiety and attachment avoidance) contributes to PIU. Another gap in the literature is that as most studies highlight the importance of maternal (over paternal) attachment security in inhibiting PIU, little research has examined the possibility of a gender difference, where maternal and paternal attachment securities may exert different influences on males and females. Methods An anonymous survey was completed by 243 undergraduate students in a public university in the U.S. Midwest. In addition to demographic information, the survey contained measurement scales to assess PIU and parental attachment (both maternal and paternal). Results Survey data show that (a) attachment anxiety, but not attachment avoidance, is significantly related to PIU and (b) gender significantly moderates this relationship, where paternal attachment anxiety leads to PIU in female students while maternal attachment anxiety contributes to PIU in male students. Conclusions This study deepens our understanding in the relationship between family upbringing, particularly parental attachment, and PIU. More specifically, attachment anxiety is found to be a significant predictor of PIU, but attachment avoidance is not. Also, contributing to the research literature is the finding of a significant gender effect in this relationship. PMID- 27554504 TI - Identifying the features of an exercise addiction: A Delphi study. AB - Objectives There remains limited consensus regarding the definition and conceptual basis of exercise addiction. An understanding of the factors motivating maintenance of addictive exercise behavior is important for appropriately targeting intervention. The aims of this study were twofold: first, to establish consensus on features of an exercise addiction using Delphi methodology and second, to identify whether these features are congruous with a conceptual model of exercise addiction adapted from the Work Craving Model. Methods A three-round Delphi process explored the views of participants regarding the features of an exercise addiction. The participants were selected from sport and exercise relevant domains, including physicians, physiotherapists, coaches, trainers, and athletes. Suggestions meeting consensus were considered with regard to the proposed conceptual model. Results and discussion Sixty-three items reached consensus. There was concordance of opinion that exercising excessively is an addiction, and therefore it was appropriate to consider the suggestions in light of the addiction-based conceptual model. Statements reaching consensus were consistent with all three components of the model: learned (negative perfectionism), behavioral (obsessive-compulsive drive), and hedonic (self-worth compensation and reduction of negative affect and withdrawal). Conclusions Delphi methodology allowed consensus to be reached regarding the features of an exercise addiction, and these features were consistent with our hypothesized conceptual model of exercise addiction. This study is the first to have applied Delphi methodology to the exercise addiction field, and therefore introduces a novel approach to exercise addiction research that can be used as a template to stimulate future examination using this technique. PMID- 27554505 TI - Physiological markers of biased decision-making in problematic Internet users. AB - Background and aims Addiction has been reliably associated with biased emotional reactions to risky choices. Problematic Internet use (PIU) is a relatively new concept and its classification as an addiction is debated. Implicit emotional responses were measured in individuals expressing nonproblematic and problematic Internet behaviors while they made risky/ambiguous decisions to explore whether they showed similar responses to those found in agreed-upon addictions. Methods The design of the study was cross sectional. Participants were adult Internet users (N = 72). All testing took place in the Psychophysics Laboratory at the University of Bath, UK. Participants were given the Iowa Gambling Task (IGT) which provides an index of an individual's ability to process and learn probabilities of reward and loss. Integration of emotions into current decision making frameworks is vital for optimal performance on the IGT and thus, skin conductance responses (SCRs) to reward, punishment, and in anticipation of both were measured to assess emotional function. Results Performance on the IGT did not differ between the groups of Internet users. However, problematic Internet users expressed increased sensitivity to punishment as revealed by stronger SCRs to trials with higher punishment magnitude. Discussion and conclusions PIU seems to differ on behavioral and physiological levels with other addictions. However, our data imply that problematic Internet users were more risk-sensitive, which is a suggestion that needs to be incorporated into in any measure and, potentially, any intervention for PIU. PMID- 27554506 TI - Dual pH with Multichannel Intraluminal Impedance Testing in the Evaluation of Subjective Laryngopharyngeal Reflux Symptoms. AB - OBJECTIVES: Minimal data exist to define the use of contemporary dual pH with multichannel intraluminal impedance (MII) probes integrating both pharyngeal acid and impedance sensors to evaluate laryngopharyngeal reflux (LPR) symptoms in a laryngology clinic population. This study was performed to review a series of patients tested with dual pH-MII for suspected LPR symptoms and to analyze pH-MII data findings for this patient cohort. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary laryngology clinic. SUBJECTS AND METHODS: Patients with symptoms suggestive of possible LPR (dysphonia, chronic cough, globus sensation, subglottic stenosis,) were evaluated with a dual pH-MII system, as well as previously validated reflux finding score (RFS) and reflux symptom index (RSI) instruments. RESULTS: A total of 109 patients were evaluated with dual pH-MII studies between 2010 and 2015, with 51 (47%) studies interpreted as "positive" for evidence of significant LPR, 43 (39%) as "negative," and 15 (14%) as "equivocal." Dual pH-MII data analysis showed that positive studies had an average of 2.84 pharyngeal acid exposures below pH 4 (vs 0.28 for negative) and 46 episodes of proximal reflux exposure (either acid or nonacid) by impedance detection (vs 30.6 for negative). RSI scores were significantly different between positive and negative studies, while RFS scores were not. CONCLUSIONS: Dual pH MII analysis is a useful supplementary tool to provide objective evidence of pharyngeal reflux exposure in patients with suspected LPR. RSI scores appear to correlate with objective evidence of acid exposure in the pharynx, while RFS scores do not. PMID- 27554507 TI - Structured Preoperative Phone Counseling by Junior Medical Staff for Improving the Consent Process for Tonsillectomy. AB - OBJECTIVE: To assess the effectiveness of preoperative phone counseling by junior medical staff for improving the standard of informed consent for tonsillectomy. STUDY DESIGN: Prospective randomized controlled trial. SETTING: District general hospital. SUBJECTS AND METHODS: A total of 43 patients undergoing tonsillectomy were randomly allocated to 2 groups. Group A (n = 25) underwent the conventional consent process by the consultant ear, nose, and throat surgeon at the time of assessment (which generally takes place 6 to 12 months prior to surgery due to wait-list times). Group B (n = 18) underwent this same consent process but received a structured preoperative phone call 2 to 3 weeks prior to the day of surgery. A preoperative questionnaire assessing the knowledge of tonsillectomy, perioperative course, and risks was completed on the day of surgery. RESULTS: Group B had a better recall of the risks of tonsillectomy, recalling 7.1 of the 10 most significant risks, as compared with 4.6 for group A (P = .017). Group B had a better awareness of tooth damage (78% vs 30% of patients, P <= .001), voice change (61 vs 19%, P = .005), and burns to lips and mouth (44% vs 8%, P = .005). Finally, 35% more patients from group B rated their understanding of tonsillectomy as good or very good (P = .017). CONCLUSION: Preoperative phone counseling by junior medical staff closer to the time of surgery reinforces and clarifies the information previously provided by senior consultants at the time of initial consent for tonsillectomy. PMID- 27554509 TI - Does the Preoperative Administration of Steroids Reduce Intraoperative Bleeding during Endoscopic Surgery of Nasal Polyps? AB - OBJECTIVES: Corticosteroids are frequently used in a range of otorhinolaryngologic conditions due to their anti-inflammatory and antiedematous properties. In this meta-analysis, we aimed to assess the role of preoperative steroids for attenuating intraoperative bleeding during endoscopic sinus surgery among patients with nasal polyps. DATA SOURCES: PubMed, SCOPUS, EMBASE, the Web of Science, and Cochrane database. METHODS: Literature was screened from January 1980 to January 2016. Five articles comparing patients who were preoperatively administered steroids (steroid groups) with patients who received a placebo or no treatment (control group) were included for analysis, which encompassed intraoperative bleeding, endoscopic surgical field visibility, operative time, and side effects during endoscopic sinus surgery. RESULTS: Intraoperative bleeding and operative time during endoscopic sinus surgery in the steroid group were significantly reduced as compared with the control group. Additionally, the preoperative administration of steroids had a significant effect on improving endoscopic surgical field visibility during sinus surgery. There were no significant adverse effects reported in the enrolled studies. In subgroup analyses of these results, steroids showed similar effects on intraoperative bleeding regardless of administration type (topical or systemic). CONCLUSION: This study demonstrated that the preoperative administration of steroids in patients with nasal polyps could effectively reduce intraoperative bleeding. However, the duration of treatment and dosing standard require further investigation, and more trials need to be included. PMID- 27554508 TI - Radiation Dose Reduction in Paranasal Sinus CT: With Feasibility of Iterative Reconstruction Technique. AB - OBJECTIVES: To (1) compare the radiation dose of low-dose computed tomography (CT) to that of standard-dose CT, (2) determine the minimum optimal radiation dose for use in patients who need endoscopic sinus surgery, and (3) assess the reliability of iterative model reconstruction. STUDY DESIGN: Prospective single institution study. SETTING: Tertiary care center. SUBJECTS AND METHODS: We recruited 48 adults with medically refractory sinusitis. Each patient underwent 4 scans with different CT parameters: 120 kV and 100 mAs (standard dose), 100 kV and 40 mAs (low dose), 100 kV and 20 mAs (very low dose), and 100 kV and 10 mAs (ultra-low dose). All CT scans were reconstructed via filtered back-projection, and ultra-low dose scans were additionally reconstructed through iterative model reconstruction. Radiation dose, image quality, and diagnostic performance were compared among the scans. RESULTS: Radiation doses decreased to 6% (ultra-low dose), 12% (very low dose), and 22% (low dose) of the standard-dose CT. The image quality of low-dose CT was similar to that of standard-dose CT. Ultra-low-dose CT with iterative model reconstruction was inferior to standard-dose CT for identifying anatomic structures, except for the optic nerve. All CT scans had 100% agreement for diagnosing rhinosinusitis. CONCLUSIONS: With low-dose CT, the radiation dose can be decreased to 22% of that of standard-dose CT without affecting the image quality. Low-dose CT can be considered the minimum optimal radiation for patients who need surgery. Iterative model reconstruction is not useful for assessing the anatomic details of the paranasal sinus on CT. PMID- 27554510 TI - Drainage Patterns to Nontraditional Nodal Regions and Level IIB in Cutaneous Head and Neck Malignancy. AB - OBJECTIVES: (1) Determine the frequency of nontraditional sentinel lymph node (SLN) locations in cutaneous head and neck malignancy and (2) determine the frequency of level IIB SLNs in cutaneous head and neck malignancy. DESIGN: Case series with chart review. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: In total, 145 consecutive sentinel lymph node biopsy (SLNB) specimens for cutaneous head and neck malignancies were reviewed from 2007 to 2015. Nodal regions were categorized into levels I to V, parotid, external jugular (EJ), perifacial, suboccipital, and postauricular regions. Primary locations were divided into scalp, forehead, cheek, ear, neck, nose, periocular, and lip. Frequencies of sentinel lymph node (SLN) locations for each primary location were determined. RESULTS: Parotid, EJ, perifacial, suboccipital, postauricular, and level IIB lymph SLNs were identified as nontraditional lymph node regions at risk in head and neck cutaneous malignancy. EJ SLNs were present in over 15% of all cases and over 25% of periocular and cheek lesions. Perifacial SLNs were frequently present in nose and lip lesions. Suboccipital and postauricular nodes were only present in scalp lesions. Level II was the most common location for a SLN. In total, 15.9% of all cases involved level IIB. Scalp and ear primary lesions were most likely to drain to level IIB. CONCLUSIONS: Nontraditional SLN locations, such as EJ, perifacial, suboccipital, postauricular, and parotid, as well as level IIB, are important sites of drainage for head and neck cutaneous malignancy. Prediction of at-risk lymph node regions is important to help guide SLNBs, elective and completion neck lymphadenectomy and radiation, and long-term observation. PMID- 27554512 TI - Health Literacy Assessment in an Otolaryngology Clinic Population. AB - OBJECTIVE: To assess health literacy in an adult tertiary care otolaryngology clinic population and to explore potential determinants of inadequate health literacy. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care otolaryngology clinic. SUBJECTS AND METHODS: The study population included all adult patients treated at 3 of Stanford University's adult otolaryngology clinic sites between March 1 and 11, 2016. Data were collected via an anonymous questionnaire. Health literacy was assessed with the Brief Health Literacy Screen. RESULTS: Ten percent of patients had inadequate health literacy. White race (odds ratio [OR], 0.23) and having English as the primary language (OR, 0.12) were associated with adequate health literacy, while high school or lower level of education (OR, 3.2) was associated with inadequate health literacy. Age, sex, and Hispanic ethnicity were not associated with health literacy. CONCLUSION: Our study highlights the need for health literacy screening in the otolaryngology clinic setting and identifies sociodemographic risk factors for inadequate health literacy. Further studies are needed to assess the impact of health literacy on patient outcomes and to test specific interventions to address health literacy and health outcomes. PMID- 27554511 TI - Patient-Reported Outcome Measures Related to Laryngopharyngeal Reflux: A Systematic Review of Instrument Development and Validation. AB - OBJECTIVES: Patient-reported outcome (PRO) measures are often used to diagnose laryngopharyngeal reflux (LPR) and monitor treatment outcomes in clinical and research settings. The present systematic review was designed to identify currently available LPR-related PRO measures and to evaluate each measure's instrument development, validation, and applicability. DATA SOURCES: MEDLINE via PubMed interface, CINAHL, and Health and Psychosocial Instrument databases were searched with relevant vocabulary and key terms related to PRO measures and LPR. REVIEW METHODS: Three investigators independently performed abstract review and full text review, applying a previously developed checklist to critically assess measurement properties of each study meeting inclusion criteria. RESULTS: Of 4947 studies reviewed, 7 LPR-related PRO measures (publication years, 1991-2010) met criteria for extraction and analysis. Two focused on globus and throat symptoms. Remaining measures were designed to assess LPR symptoms and monitor treatment outcomes in patients. None met all checklist criteria. Only 2 of 7 used patient input to devise item content, and 2 of 7 assessed responsiveness to change. Thematic deficiencies in current LPR-related measures are inadequately demonstrated: content validity, construct validity, plan for interpretation, and literacy level assessment. CONCLUSION: Laryngopharyngeal reflux is often diagnosed according to symptoms. Currently available LPR-related PRO measures used to symptomatically identify suspected LPR patients have disparate developmental rigor and important methodological deficiencies. Care should be exercised to understand the measurement characteristics and contextual relevance before applying these PRO measures for clinical, research, or quality initiatives. PMID- 27554513 TI - Uvulopalatopharyngoplasty: Does Multilevel Surgery Increase Risk? AB - OBJECTIVES: (1) Determine the rate of postoperative complications, reoperation, readmission, and death after uvulopalatopharyngoplasty (UPPP) for sleep apnea through multi-institutional clinical data. (2) Compare outcomes of UPPP between multilevel and single-level procedures for the treatment of sleep apnea. STUDY DESIGN: Retrospective database analysis. METHODS: The American College of Surgeons National Surgical Quality Improvement Program-a nationally validated, prospective, multi-institutional database from 2005 to 2013-was analyzed for patients who underwent UPPP, per corresponding Current Procedural Terminology codes. Patients were categorized into 3 groups: UPPP alone, UPPP + nasal cavity (NC), and UPPP + base of tongue (BOT). Perioperative outcome measures of interest include surgical/medical complications, reoperation, readmission, and death. Comparisons were made among surgical groups through univariate cross-sectional analysis. RESULTS: A total of 1079 patients underwent UPPP; 413 patients had UPPP + NC; and 200 patients had UPPP + BOT procedures. One death was reported for the entire cohort of patients. Among all 3 groups (UPPP, UPPP + NC, and UPPP + BOT), no differences were noted in the rates of medical complications (P = .445), surgical complications (P = .396), reoperation (P = .332), and readmission (P = .447). However, the length of hospital stay in days was greatest for the UPPP + BOT group (UPPP, 0.81 +/- 0.69; UPPP + NC, 0.87 +/- 0.90; UPPP + BOT, 1.50 +/- 2.70; P < .001). CONCLUSION: These national data demonstrate no significant increase in risk when UPPP is performed as a single- or multilevel procedure. When indicated, UPPP with multilevel procedures may be safely performed for treatment of sleep apnea. These data set a benchmark for perioperative risk in UPPP surgery and will prove useful for counseling patients. PMID- 27554514 TI - Laryngology in Art: The Portrait of Dr Wilhelm Mayer-Hermann. AB - Otto Dix's portrait of the laryngologist Dr Wilhelm Mayer-Hermann represents a shining example of Neue Sachlichkeit, or New Objectivity, offering a return to unsentimental reality and a focus on the objective world, as opposed to the more abstract and idealistic tendencies of expressionism. However, precious little is known about the subject of the portrait. This article examines the portrait and attempts to shed light on the life and career of the Dr Wilhelm Mayer-Hermann. PMID- 27554515 TI - The History and Evolution of Surgery on the Vestibular Labyrinth. AB - The history of surgery on the vestibular labyrinth is rich but sparsely documented in the literature. The story begins over a century ago with the labyrinthectomy in an era that consisted exclusively of ablative surgery for infection or vertigo. Improved understanding of vestibular physiology and pathology produced an era of selective ablation and hearing preservation that includes semicircular canal occlusion for benign paroxysmal positional vertigo. An era of restoration began with a discovery of superior semicircular canal dehiscence and its repair. The final era of vestibular replacement is upon us as the possibility of successful prosthetic vestibular implantation becomes reality. PMID- 27554516 TI - The Impact of Angiotensin-Modulating Antihypertensives on Time Interval to Revision Surgery for Nasal Polyps. AB - OBJECTIVE/HYPOTHESIS: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to suppress expression of periostin, a matricellular protein that is markedly elevated in nasal polyp tissue. The purpose of this study was to determine whether use of these antihypertensive agents affects the time to revision sinus surgery in patients with polyp regrowth. STUDY DESIGN: Case series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS: Records were reviewed for 330 patients who underwent >=2 operations for chronic sinusitis with nasal polyps from April 1987 through August 2015. The time between surgical interventions was compared with patient demographics and clinical characteristics, including use of ACEIs and ARBs. RESULTS: Sixty patients were taking ACEIs or ARBs during the study period, of which 32 had concurrent asthma. The mean interval between polyp operations was 61.0 +/- 45.2 months (range, 2-228.6 months). Among patients with asthma (n = 197), the mean time to revision surgery was prolonged by >2 years for those taking ACEIs or ARBs (81.0 vs 54.5 months, P = .006). A similar impact on time to revision surgery was not observed for nonasthmatics taking these medications (61.0 vs 65.2 months, P = .655). CONCLUSION: Use of ACEIs and ARBs is associated with an increased time to revision sinus surgery among patients with concurrent nasal polyps and asthma. A possible mechanism of this observed effect is suppression of periostin expression through inhibition of the angiotensin pathway. PMID- 27554517 TI - Developing Quality Measures for Adult Cochlear Implant Centers: Preliminary Findings. AB - The study objective was to develop quality measures for adult cochlear implant centers. A modified Delphi design beginning with focus groups of surgeons and audiologists was used, as adapted from the American College of Cardiology / American Heart Association method for creating quality measures. Two academic cochlear implant programs and 1 private program participated. Qualitative focus group analysis yielded 58 candidate measures. An additional 5 candidate measures were added from a systematic review of the literature. After exclusion of pediatric measures, structure measures, and process measures and discussion of details and implications of each measure, 8 measures remained as the preliminary Adult Cochlear Implant Outcome (CI-OUTCOME) Measure Set. This study provides a preliminary set of measures for evaluating the quality of adult cochlear implant centers, based on input from implant surgeons and audiologists. The next step will be to gather feedback from implant patients. PMID- 27554518 TI - TLR2 controls random motility, while TLR7 regulates chemotaxis of microglial cells via distinct pathways. AB - Microglial cells are the pathologic sensor of the brain, and any pathologic event triggers microglial activation, which involves migration of these cells to a lesion site. Employing different migration assays, we show that ligands for toll like receptor (TLR) 2 stimulate random motility, while TLR7 ligands are chemoattractants. The subtype specificity of the TLR ligands was verified by using different TLR-deficient (TLRKO) mouse lines. PI3K and Rac inhibition impairs both TLR2- and TLR7-stimulated microglial migration. In contrast, Akt phosphorylation is only required for the TLR2-, but not for the TLR7-stimulated pathway. Interestingly, P2Y12 receptor signaling is involved in the TLR2 activation-induced microglial migration but not TLR7. Furthermore, TLR7 mRNA expression is down-regulated by TLR2 and TLR7 activation. We conclude that TLRs control the migratory behavior of microglia in a distinct manner. PMID- 27554520 TI - Combined HRT may raise breast cancer risk, study finds. PMID- 27554519 TI - In vivo erosion of orthopedic screws prepared from nacre (mother of pearl). AB - BACKGROUND: Biodegradable biomaterials have been proposed to prepare orthopedic devices. Nacre is a natural aragonitic material made of calcium carbonate and is bioerodible. WORKING HYPOTHESIS: We postulated that nacre is biodegradable without provoking bone erosion and favors bone apposition. MATERIAL AND METHODS: We prepared orthopedic screws from nacre of the giant oyster Pinctada maxima. Threaded screws (3.5mm diameter) were implanted in 6 ewes in the upper tibial metaphysis (3 to 4 screws per animal). Their trajectory was transcortical and intramedullary to the opposite cortex. Animals were kept for 3months (n=2) and 6 months (n=4). They did not develop local inflammation. Before euthanasia, they received a double calcein labeling. Bone samples were analyzed by X-ray nanotomography and histology after embedding in poly(methyl methacrylate). The fractal dimension of the screw profiles (measured by the box-counting method) was used to quantify surface erosion. RESULTS: 3D nanotomography showed a gradual erosion of the threads, which was confirmed by a decreased fractal dimension. Histologically, multinucleated cells (non-osteoclastic appearance) were visible at the surface of the screws. No ruffled border was seen in these cells but they had extensions creeping in the organic matter between the aragonite tablets. Bone apposition was noted in the transcortical path of the screws with limited osteoconduction at the endosteum. Mineralization rate was increased in these zones composed of woven bone in contact with the nacre. DISCUSSION AND CONCLUSION: Screws prepared from nacre have the advantage of an in vivo resorbability by macrophage-derived cells and an osteoconductive apposition in contact with the material without triggering a local inflammatory reaction. PMID- 27554521 TI - "Our organs have a purpose": body image acceptance in Latina breast cancer survivors. AB - OBJECTIVE: Studies examining body image concerns among breast cancer survivors have primarily captured the experiences of non-Latina white women. Thus, little is known about body image concerns among Latinas. To address this gap, we examined Latina breast cancer survivors' lived experiences related to body image. METHODS: Twenty-seven Latina breast cancer survivors provided data through focus groups and individual interviews as part of a larger study conducted by the first author. In the current paper, we conducted a secondary thematic analysis to uncover women's experiences unique to body image concerns. RESULTS: We identified 2 themes related to women's experiences with body image: (a) perceptions of loss and reconstruction and (b) process of achieving body image acceptance. The salience of these themes varied as a function of survivorship stage and type of surgery. CONCLUSIONS: Body image concerns are distressing for Latina breast cancer survivors. Accepting their altered appearance was an ongoing and complex process. Clinical implications include the need for psychoeducational programs and tailored interventions to enhance women's body image acceptance. PMID- 27554522 TI - Two-Step Chemoenzymatic Detection of N-Acetylneuraminic Acid-alpha(2-3)-Galactose Glycans. AB - Sialic acids are typically linked alpha(2-3) or alpha(2-6) to the galactose that located at the non-reducing terminal end of glycans, playing important but distinct roles in a variety of biological and pathological processes. However, details about their respective roles are still largely unknown due to the lack of an effective analytical technique. Herein, a two-step chemoenzymatic approach for the rapid and sensitive detection of N-acetylneuraminic acid-alpha(2-3)-galactose glycans is described. PMID- 27554523 TI - Metastatic Giant Condyloma Acuminata (Buschke-Lowenstein Tumor). PMID- 27554524 TI - Primary CNS Leiomyosarcoma in an Immunocompetent Patient. PMID- 27554525 TI - Use and Appreciation of a Tailored Self-Management eHealth Intervention for Early Cancer Survivors: Process Evaluation of a Randomized Controlled Trial. AB - BACKGROUND: A fully automated computer-tailored Web-based self-management intervention, Kanker Nazorg Wijzer (KNW [Cancer Aftercare Guide]), was developed to support early cancer survivors to adequately cope with psychosocial complaints and to promote a healthy lifestyle. The KNW self-management training modules target the following topics: return to work, fatigue, anxiety and depression, relationships, physical activity, diet, and smoking cessation. Participants were guided to relevant modules by personalized module referral advice that was based on participants' current complaints and identified needs. OBJECTIVE: The aim of this study was to evaluate the adherence to the module referral advice, examine the KNW module use and its predictors, and describe the appreciation of the KNW and its predictors. Additionally, we explored predictors of personal relevance. METHODS: This process evaluation was conducted as part of a randomized controlled trial. Early cancer survivors with various types of cancer were recruited from 21 Dutch hospitals. Data from online self-report questionnaires and logging data were analyzed from participants allocated to the intervention condition. Chi square tests were applied to assess the adherence to the module referral advice, negative binominal regression analysis was used to identify predictors of module use, multiple linear regression analysis was applied to identify predictors of the appreciation, and ordered logistic regression analysis was conducted to explore possible predictors of perceived personal relevance. RESULTS: From the respondents (N=231; mean age 55.6, SD 11.5; 79.2% female [183/231]), 98.3% (227/231) were referred to one or more KNW modules (mean 2.9, SD 1.5), and 85.7% (198/231) of participants visited at least one module (mean 2.1, SD 1.6). Significant positive associations were found between the referral to specific modules (range 1-7) and the use of corresponding modules. The likelihoods of visiting modules were higher when respondents were referred to those modules by the module referral advice. Predictors of visiting a higher number of modules were a higher number of referrals by the module referral advice (beta=.136, P=.009), and having a partner was significantly related with a lower number of modules used (beta=-.256, P=.044). Overall appreciation was high (mean 7.5, SD 1.2; scale 1-10) and was significantly predicted by a higher perceived personal relevance (beta=.623, P=.000). None of the demographic and cancer-related characteristics significantly predicted the perceived personal relevance. CONCLUSIONS: The KNW in general and more specifically the KNW modules were well used and highly appreciated by early cancer survivors. Indications were found that the module referral advice might be a meaningful intervention component to guide the users in following a preferred selection of modules. These results indicate that the fully automated Web-based KNW provides personal relevant and valuable information and support for early cancer survivors. Therefore, this intervention can complement usual cancer aftercare and may serve as a first step in a stepped-care approach. TRIAL REGISTRATION: Nederlands Trial Register: NTR3375; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3375 (Archived by WebCite at http://www.webcitation.org/6jo4jO7kb). PMID- 27554526 TI - Benchmarking of the Oxford Nanopore MinION sequencing for quantitative and qualitative assessment of cDNA populations. AB - To assess the performance of the Oxford Nanopore Technologies MinION sequencing platform, cDNAs from the External RNA Controls Consortium (ERCC) RNA Spike-In mix were sequenced. This mix mimics mammalian mRNA species and consists of 92 polyadenylated transcripts with known concentration. cDNA libraries were generated using a template switching protocol to facilitate the direct comparison between different sequencing platforms. The MinION performance was assessed for its ability to sequence the cDNAs directly with good accuracy in terms of abundance and full length. The abundance of the ERCC cDNA molecules sequenced by MinION agreed with their expected concentration. No length or GC content bias was observed. The majority of cDNAs were sequenced as full length. Additionally, a complex cDNA population derived from a human HEK-293 cell line was sequenced on an Illumina HiSeq 2500, PacBio RS II and ONT MinION platforms. We observed that there was a good agreement in the measured cDNA abundance between PacBio RS II and ONT MinION (rpearson = 0.82, isoforms with length more than 700bp) and between Illumina HiSeq 2500 and ONT MinION (rpearson = 0.75). This indicates that the ONT MinION can sequence quantitatively both long and short full length cDNA molecules. PMID- 27554528 TI - I can see where you would be: Patterns of fMRI activity reveal imagined landmarks. AB - Visual mental imagery arises when perceptual information is accessed from memory, originating the experience of "seeing with the mind's eye". Different content dependent brain areas in the human ventral visual stream are activated during visual mental imagery, similarly to what happens during visual perception. The neural patterns within these regions, but not in the early visual cortex, are similar during imagery and perception, suggesting that, in the absence of perceptual stimulation, content-dependent brain areas are able to re-instantiate specific neural patterns allowing for mental imagery. However, it remains unknown whether these areas contain adequate neural representations that create mental images or need to interact with other regions in the brain, such as the hippocampus (HC), to access the necessary information from memory. To test this hypothesis, we used functional magnetic resonance imaging and both multivoxel pattern classification and psychophysiological interaction analyses. Participants were scanned while viewing or imagining scenes of familiar environments. We found that the identity of familiar places can be decoded from the neural patterns in the parahippocampal place area (PPA), retrosplenial complex/parieto-occipital sulcus (RSC/POS) and HC, during both imagery and perception, and that item specific information from perceived places was re-instantiated during mental imagery of the same places and vice versa. Furthermore, the right PPA significantly interacted with the right HC and RSC/POS according to the performed task. Specifically, the functional coupling between PPA and HC was higher during mental imagery, whereas the functional coupling between PPA and RSC/POS was higher during perception. Our investigation provides an important contribution to the understanding of how the brain uses previously acquired knowledge to build a mental representation of the world. PMID- 27554527 TI - Retinotopic patterns of functional connectivity between V1 and large-scale brain networks during resting fixation. AB - Psychophysical and neurobiological evidence suggests that central and peripheral vision are specialized for different functions. This specialization of function might be expected to lead to differences in the large-scale functional interactions of early cortical areas that represent central and peripheral visual space. Here, we characterize differences in whole-brain functional connectivity among sectors in primary visual cortex (V1) corresponding to central, near peripheral, and far-peripheral vision during resting fixation. Importantly, our analyses reveal that eccentricity sectors in V1 have different functional connectivity with non-visual areas associated with large-scale brain networks. Regions associated with the fronto-parietal control network are most strongly connected with central sectors of V1, regions associated with the cingulo opercular control network are most strongly connected with near-peripheral sectors of V1, and regions associated with the default mode and auditory networks are most strongly connected with far-peripheral sectors of V1. Additional analyses suggest that similar patterns are present during eyes-closed rest. These results suggest that different types of visual information may be prioritized by large-scale brain networks with distinct functional profiles, and provide insights into how the small-scale functional specialization within early visual regions such as V1 relates to the large-scale organization of functionally distinct whole-brain networks. PMID- 27554529 TI - Imaging structural covariance in the development of intelligence. AB - Verbal and non-verbal intelligence in children is highly correlated, and thus, it has been difficult to differentiate their neural substrates. Nevertheless, recent studies have shown that verbal and non-verbal intelligence can be dissociated and focal cortical regions corresponding to each have been demonstrated. However, the pattern of structural covariance corresponding to verbal and non-verbal intelligence remains unexplored. In this study, we used 586 longitudinal anatomical MRI scans of subjects aged 6-18 years, who had concurrent intelligence quotient (IQ) testing on the Wechsler Abbreviated Scale of Intelligence. Structural covariance networks (SCNs) were constructed using interregional correlations in cortical thickness for low-IQ (Performance IQ=100+/-8, Verbal IQ=100+/-7) and high-IQ (PIQ=121+/-8, VIQ=120+/-9) groups. From low- to high-VIQ group, we observed constrained patterns of anatomical coupling among cortical regions, complemented by observations of higher global efficiency and modularity, and lower local efficiency in high-VIQ group, suggesting a shift towards a more optimal topological organization. Analysis of nodal topological properties (regional efficiency and participation coefficient) revealed greater involvement of left-hemispheric language related regions including inferior frontal and superior temporal gyri for high-VIQ group. From low- to high-PIQ group, we did not observe significant differences in anatomical coupling patterns, global and nodal topological properties. Our findings indicate that people with higher verbal intelligence have structural brain differences from people with lower verbal intelligence - not only in localized cortical regions, but also in the patterns of anatomical coupling among widely distributed cortical regions, possibly resulting to a system-level reorganization that might lead to a more efficient organization in high-VIQ group. PMID- 27554530 TI - Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans. AB - Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit. PMID- 27554532 TI - Rapid top-down control over template-guided attention shifts to multiple objects. AB - Previous research has shown that when observers search for targets defined by a particular colour, attention can be directed rapidly and independently to two target objects that appear in close temporal proximity. We investigated how such rapid attention shifts are modulated by task instructions to selectively attend versus ignore one of these objects. Two search displays that both contained a colour-defined target and a distractor in a different colour were presented in rapid succession, with a stimulus onset asynchrony (SOA) of 100ms. In different blocks, participants were instructed to attend and respond to target-colour objects in the first display and to ignore these objects in the second display, or vice versa. N2pc components were measured to track the allocation of spatial attention to target-colour objects in these two displays. When participants responded to the second display, irrelevant target-colour objects in the first display still triggered N2pc components, demonstrating task-set contingent attentional capture while a feature-specific target template is active. Critically, when participants responded to the first display instead, no N2pc was elicited by target-colour items in the second display, indicating that they no longer rapidly captured attention. However, these items still elicited a longer latency contralateral negativity (SPCN component), suggesting that attention was oriented towards template-matching objects in working memory. This dissociation between N2pc and SPCN components shows that rapid attentional capture and subsequent attentional selection processes within working memory can be independent. We suggest that early attentional orienting mechanisms can be inhibited when task-set matching objects are no longer task-relevant, and that this type of inhibitory control is a rapid but transient process. PMID- 27554533 TI - Evaluation of cortical local field potential diffusion in stereotactic electro encephalography recordings: A glimpse on white matter signal. AB - While there is a strong interest in meso-scale field potential recording using intracranial electroencephalography with penetrating depth electrodes (i.e. stereotactic EEG or S-EEG) in humans, the signal recorded in the white matter remains ignored. White matter is generally considered electrically neutral and often included in the reference montage. Moreover, re-referencing electrophysiological data is a critical preprocessing choice that could drastically impact signal content and consequently the results of any given analysis. In the present stereotactic electroencephalography study, we first illustrate empirically the consequences of commonly used references (subdermal, white matter, global average, local montage) on inter-electrode signal correlation. Since most of these reference montages incorporate white matter signal, we next consider the difference between signals recorded in cortical gray matter and white matter. Our results reveal that electrode contacts located in the white matter record a mixture of activity, with part arising from the volume conduction (zero time delay) of activity from nearby gray matter. Furthermore, our analysis shows that white matter signal may be correlated with distant gray matter signal. While residual passive electrical spread from nearby matter may account for this relationship, our results suggest the possibility that this long distance correlation arises from the white matter fiber tracts themselves (i.e. activity from distant gray matter traveling along axonal fibers with time lag larger than zero); yet definitive conclusions about the origin of the white matter signal would require further experimental substantiation. By characterizing the properties of signals recorded in white matter and in gray matter, this study illustrates the importance of including anatomical prior knowledge when analyzing S-EEG data. PMID- 27554531 TI - Phase-amplitude coupling and the BOLD signal: A simultaneous intracranial EEG (icEEG) - fMRI study in humans performing a finger-tapping task. AB - Although it has been consistently found that local blood-oxygen-level-dependent (BOLD) changes are better modelled by a combination of the power of multiple EEG frequency bands rather than by the power of a unique band alone, the local electro-haemodynamic coupling function is not yet fully characterised. Electrophysiological studies have revealed that the strength of the coupling between the phase of low- and the amplitude of high- frequency EEG activities (phase-amplitude coupling - PAC) has an important role in brain function in general, and in preparation and execution of movement in particular. Using electrocorticographic (ECoG) and functional magnetic resonance imaging (fMRI) data recorded simultaneously in humans performing a finger-tapping task, we investigated the single-trial relationship between the amplitude of the BOLD signal and the strength of PAC and the power of alpha, beta, and gamma bands, at a local level. In line with previous studies, we found a positive correlation for the gamma band, and negative correlations for the PACbetagamma strength, and the alpha and beta bands. More importantly, we found that the PACbetagamma strength explained variance of the amplitude of the BOLD signal that was not explained by a combination of the alpha, beta, and gamma band powers. Our main finding sheds further light on the distinct nature of PAC as a functionally relevant mechanism and suggests that the sensitivity of EEG-informed fMRI studies may increase by including the PAC strength in the BOLD signal model, in addition to the power of the low- and high- frequency EEG bands. PMID- 27554535 TI - Obstetrical and neonatal case definitions for immunization safety data. PMID- 27554534 TI - A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes. AB - BACKGROUND: Rabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes. METHODS: This was a randomized active-controlled non-inferiority study in 180 individuals (age 5years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures). The participants received either Rabivax-S (1mL IM; five doses), Rabivax-S (0.1mL ID; eight doses) or purified chick embryo cell vaccine (PCEC, Rabipur(r)) (1mL IM; five doses). The IM doses were given on Day 0, 3, 7, 14 and 28 while the ID doses were given on days 0, 3, 7 and 28. Category III patients also received a human rabies immunoglobulin (HRIG) on Day 0. Adverse events (AEs) were recorded with diary cards till day 42. Rabies neutralizing antibody levels were measured on day 0, 7, 14, 28 and 42. RESULTS: In both the category II and III patients, the geometric mean concentration (GMC) ratios of Rabivax-S IM and Rabivax-S ID groups to PCEC IM were more than 1, thus proving the non-inferiority. GMCs were similar or higher in Rabivax-S groups at all the time points. Seroresponse against rabies (RFFIT titre?0.5IU/mL) was achieved in all participants. Mostly mild local and systemic adverse events were reported across the three groups and all resolved without sequelae. CONCLUSIONS: Rabivax-S was well tolerated and showed immunogenicity comparable to a licensed rabies vaccine by both IM and ID routes in post-exposure prophylaxis. Registry No.: CTRI/2012/11/003135. PMID- 27554536 TI - Effect of growth differentiation factor-9 (GDF-9) on the progression of buffalo follicles in vitrified-warmed ovarian tissues. AB - To improve the reproductive performance of water buffalo to level can satisfy our needs, the mechanisms controlling ovarian follicular growth and development should be thoroughly investigated. Therefore, in this study, the expressions of growth differentiation factor-9 (GDF-9) in buffalo ovaries were examined by immunohistochemistry, and the effects of GDF-9 treatment on follicle progression were investigated using a buffalo ovary organ culture system. Frozen-thawed buffalo ovarian follicles within slices of ovarian cortical tissue were cultured for 14 days in the presence or absence of GDF-9. After culture, ovarian slices were fixed, sectioned and stained. The follicles were morphologically analysed and counted. Expression pattern of GDF-9 was detected in oocytes from primordial follicles onwards, besides, also presented in granulosa cells. Moreover, GDF-9 was detected in mural granulosa cells and theca cells of pre-antral follicles. In antral follicles, cumulus cells and theca cells displayed positive expression of GDF-9. In corpora lutea, GDF-9 was expressed in both granulosa and theca lutein cells. After in vitro culture, there was no difference in the number of primordial follicles between cultured plus GDF-9 and cultured control that indicated the GDF-9 treatment has no effect on the primordial to primary follicle transition. GDF-9 treatment caused a significant decrease in the number of primary and secondary follicles compared with controls accompanied with a significant increase in pre-antral and antral follicles. These results suggest that a larger number of primary and secondary follicles were stimulated to progress to later developmental stages when treated with GDF-9. Vitrification/warming of buffalo ovarian tissue had a little remarkable effect, in contrast to culturing for 14 days, on the expression of GDF-9. In conclusion, treatment with GDF-9 was found to promote progression of primary follicle that could provide an alternative approach to stimulate early follicle development and to improve therapies for the most common infertility problem in buffaloes (ovarian inactivity). PMID- 27554537 TI - Evolution of magnetic properties and exchange interactions in Ru doped YbCrO3. AB - Magnetic properties of YbCr1-x Ru x O3 as a function of temperature and magnetic field have been investigated to explore the intriguing magnetic phenomena in rare earth orthochromites. A quantitative analysis of x-ray photoelectron spectroscopy confirms the mixed valence state (Yb(3+) and Yb(2+)) of Yb ions for the highest doped sample. Field-cooled magnetization reveals a broad peak around 75 K and then becomes zero at about 20-24 K, due to the antiparallel coupling between Cr(3+) and Yb(3+) moments. An increase of the Ru(4+) ion concentration leads to a slight increase of compensation temperature T comp from 20 to 24 K, but the Neel temperature remains constant. A larger value of the magnetic moment of Yb ions gives rise to negative magnetization at low temperature. An external magnetic field significantly modifies the temperature dependent magnetization. Simulation of temperature dependent magnetization data, below T N, based on the three (two) magnetic sub-lattice model predicts stronger intra-sublattice exchange interaction than that of inter-sublattice. Thermal hysteresis and Arrot plots suggest first order magnetic phase transition. Random substitution of Ru(4+) ion reduces the magnetic relaxation time. Weak ferromagnetic component in canted antiferromagnetic system and negative internal magnetic field cause zero-field cooled exchange bias effect. Large magnetocrystalline anisotropy associated with Ru creates high coercivity in the Ru doped sample. A maximum value of magnetocaloric effect is found around the antiferromagnetic ordering of Yb(3+) ions. Antiferromagnetic transition at about 120 K and temperature induced magnetization reversal lead to normal and inverse magnetocaloric effects in the same material. PMID- 27554538 TI - We shall all make mistakes. PMID- 27554539 TI - We must educate the doctors that society needs. PMID- 27554540 TI - Equal treatment for myocardial infarction patients? PMID- 27554541 TI - An unexpected death? PMID- 27554542 TI - [Not Available]. PMID- 27554543 TI - [Not Available]. PMID- 27554544 TI - [Not Available]. PMID- 27554545 TI - [Not Available]. PMID- 27554546 TI - [Not Available]. PMID- 27554547 TI - [Not Available]. PMID- 27554548 TI - [Not Available]. PMID- 27554549 TI - [Not Available]. PMID- 27554550 TI - [Not Available]. PMID- 27554551 TI - [New medical curriculum - Oslo 2014]. PMID- 27554553 TI - [Ultrasound as an integral part of the medical education]. PMID- 27554552 TI - [Oslo 2014 from the student perspective]. PMID- 27554554 TI - [Personalized medicine - a technological concern?]. PMID- 27554555 TI - [Together for patients with hereditary neuromuscular conditions]. PMID- 27554556 TI - [Intrauterine spiral and contraceptive implants are best for prevention of unwanted pregnancies]. PMID- 27554557 TI - [Courses in coping with depression - for the benefit of whom?]. PMID- 27554558 TI - [Patient admission beyond capacity and danger limit for mortality]. PMID- 27554559 TI - [Myocardial infarction, saturated fat and cholesterol]. PMID- 27554560 TI - ["Chronic ischemic changes" - a misleading term]. PMID- 27554561 TI - [Not Available]. PMID- 27554562 TI - Gender differences in the assessment and treatment of myocardial infarction. AB - BACKGROUND: Previous studies have shown that there are gender-related differences in the assessment and treatment of myocardial infarction, despite international guidelines that prescribe identical treatment for women and men. We investigated whether these differences occurred in Norway. MATERIAL AND METHOD: All patients admitted to Norwegian hospitals with myocardial infarction from 1 January 2013 to 31 December 2014 and registered in the Norwegian Myocardial Infarction Registry were included. Data from the registry were used to analyse differences in the assessment, treatment, complications and survival of women and men in different age groups. RESULTS: A total of 26 447 myocardial infarctions were registered in the Norwegian Myocardial Infarction Registry in the period 2013 - 2014. Fewer women than men were assessed by means of coronary angiography. Percutaneous coronary intervention (PCI) was used to virtually the same extent for both genders if coronary stenosis was found. Women were recommended secondary prophylactic medication to a lesser extent than men. There were no major differences between men and women in the incidence of complications in the course following myocardial infarction or in survival. INTERPRETATION: Fewer women than men suffering acute myocardial infarction were assessed by means of coronary angiography, and women were recommended secondary prophylactic medication less often than men. The reason for the gender differences is not known, but comorbidity and a potentially greater risk of adverse reactions in women may be contributory factors. The different views of doctors providing treatment may also play a part. PMID- 27554563 TI - Following the Utoya attack - who received early assistance? AB - BACKGROUND: Following the terror attack on Utoya on 22 July 2011, the Norwegian Directorate of Health recommended a proactive model of follow-up in the municipalities. According to this model, crisis teams were to rapidly contact the survivors, and all survivors were to be assigned a fixed contact person in the municipality. The aim was to ensure early assistance and continuity of follow-up. In this study we investigate whether there were geographical differences in the assistance measures provided. MATERIAL AND METHOD: The study includes 321 of 495 survivors of the Utoya attack. The participants were interviewed 4 - 5 months after the terror attack. We studied whether there were differences in the proportion of survivors who received proactive follow-up and other health services based on health region or centrality of the municipality of residence. RESULTS: The study showed that there were geographical differences in the health assistance provided, whereby a lower proportion of survivors received proactive follow-up in Oslo compared to the country as a whole. In Oslo, 66 % of the survivors reported that they had been contacted by a crisis team and 61 % that they had been assigned a contact person. In smaller central municipalities, 88 - 98 % reported contact with a crisis team and 85 - 91 % reported that they had been assigned a contact person. INTERPRETATION: The findings must be seen in the context of the particularly severe effect on Oslo of the terror attacks on 22 July 2011. Organisational factors in the municipality may also have had an impact on the outcome. PMID- 27554564 TI - [Atypical mycobacteria and Lady Windermere]. PMID- 27554566 TI - A woman in her thirties with cough, tremor, agitation and visual disturbances. PMID- 27554565 TI - A patient with sepsis following a burn injury in Pakistan. PMID- 27554567 TI - [Predator attacks in Norway]. PMID- 27554568 TI - [The devil on the back]. PMID- 27554569 TI - The Sun King's anal fistula. PMID- 27554570 TI - The Norwegian Medical Association's lack of clarity on "active help in dying". PMID- 27554571 TI - [Not "fast track" in Norwegian]. PMID- 27554572 TI - [Not Available]. PMID- 27554574 TI - [Not Available]. PMID- 27554573 TI - [Not Available]. PMID- 27554575 TI - [Motivated interns starts in general practice, but do they stay?]. PMID- 27554576 TI - [Medical certificates for use by The Norwegian Child Welfare Services]. PMID- 27554578 TI - [Not Available]. PMID- 27554577 TI - [Not Available]. PMID- 27554579 TI - [Not Available]. PMID- 27554580 TI - [Not Available]. PMID- 27554581 TI - [Not Available]. PMID- 27554582 TI - [Not Available]. PMID- 27554583 TI - Racial Disparities in Histology and Short-Term Renal Functional Outcomes Following Robotic Nephron-Sparing Surgery. AB - PURPOSE: To identify variations in renal function and histology between Caucasian Americans (CA) and African Americans (AA) undergoing robotic nephron-sparing surgery (NSS). METHODS: A retrospective chart review was performed on patients who underwent NSS. Multivariate analysis identified factors affecting postoperative estimated glomerular filtration rate (eGFR). Histology was re reviewed by pathology to confirm papillary type. RESULTS: A total of 331 patients underwent NSS: CA (n = 212), AA (n = 105), Hispanic (n = 10), and other (n = 4). AA average age (60.1 years) was lower than CA (62.3 years) (P < .001), with a higher proportion of AA women (46%) than CA (37%) (P = .021). AA had a higher incidence of diabetes (58.2%) and hypertension (93.9%). Preoperative average eGFR was similar: 70.35 mL/min for AA versus 69.06 mL/min for CA. Average postoperative eGFR was 50.59 mL/min for AA and 57.85 mL/min for CA. Postoperative creatinine increased more in AA (0.44 mg/dL) versus CA (0.33 mg/dL) (P < .001) even when stratified by pathological stage. Clear cell renal cell carcinoma (RCC) was the most common histology with AA (45%) and CA (60%). A greater than 2-fold higher incidence of papillary RCC was observed in AA (31%) versus CA (13%). AA exhibited a greater proportion of high-grade or type 2 papillary RCC (40% and 30%) versus CA (25% and 13%). CONCLUSIONS: AA patients were treated at a younger age, with a larger proportion of women. Postoperatively, AA experienced a greater increase in serum creatinine. Final histology demonstrated greater papillary RCC incidence in AA and increased likelihood for type 2 papillary RCC, a more aggressive histology. PMID- 27554584 TI - Adjuvant Chemotherapy After Radical Cystectomy for Urothelial Bladder Cancer: Outcome and Prognostic Factors for Survival in a French Multicenter, Contemporary Cohort. AB - BACKGROUND: In the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. PATIENTS AND METHODS: We retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. RESULTS: The median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT >=3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. CONCLUSION: Classical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment. PMID- 27554586 TI - A Systematic Review of the Incidence and Risk Factors for Taxane Acute Pain Syndrome in Patients Receiving Taxane-Based Chemotherapy for Prostate Cancer. AB - Taxane acute pain syndrome (TAPS) is characterized by myalgia and arthralgia starting 24 to 48 hours after taxane-based chemotherapy and lasting <= 7 days. Little is known about its incidence and predisposing factors in patients with prostate cancer. A systematic review was performed to identify studies reporting the incidence and risk factors for TAPS in patients receiving taxane-based chemotherapy for prostate cancer. Embase, Ovid Medline, and other nonindexed citations were searched from 1947 to July 7, 2015. Randomized trials and prospective observational studies reporting the outcomes for prostate cancer patients who had received taxane-based chemotherapy were assessed. Four reviewers independently screened the citations and full text reports for data collection. Of 980 citations, 5 studies (2710 patients) met the eligibility criteria. The incidence of myalgia and arthralgia was reported in 4 trials (14%, [29% and 38%], 44.2%, and 46%). TAPS was not reported with cabazitaxel chemotherapy. Clinical risk factors were identified in 4 studies, suggesting that TAPS was numerically more common in the castrate-resistant setting and when concurrent medications (eg, corticosteroids) were not used. Although the TAPS incidence has been poorly reported in clinical practice, the results of the present study suggest that arthralgia and myalgia are a common toxicity in patients with prostate cancer. An improved and universal definition of TAPS, patient-directed reporting of TAPS, and improved standardized assessments are needed to better identify patients at the greatest risk of experiencing TAPS and improving patient care. PMID- 27554585 TI - Novel Angiogenesis Markers as Long-Term Prognostic Factors in Patients With Renal Cell Cancer. AB - OBJECTIVE: To evaluate Ang-2 expression alone and in combination with expression of cell proliferation and cell survival markers (MIB-1 and Bcl-2) and angiogenesis markers (VEGFR3 and CD31), and the associations of these markers with renal cell cancer (RCC) in long-term survival. PATIENTS AND METHODS: Our study included 224 patients with RCC who were treated before the availability of antiangiogenic agents between 1985 and 1995, at the Pirkanmaa Hospital District in Finland. All tumor samples were reclassified and reevaluated by an experienced uropathologist, and parallel tissue microarrays (TMA) were performed for immunohistochemical analysis. Kaplan-Meier's survival estimation method and Cox proportional hazards models were used for survival analysis. RESULTS: The percentage of Ang-2 expression in the tumor area varied from 0.07 to 25.65. Ang-2 expression was significantly associated with the tumor grade and stage, as well as the MIB-1, Bcl-2, and VEGFR3 expression (P = .042, P = .019, P = .039, P = .013, and P = .005, respectively). The highest Ang-2 expression predicted better survival, P < .05. High Bcl-2 and low MIB-1 expression combined with Ang-2 expression was associated with better survival. Multivariate analysis showed poorer survival in patients with low Ang-2 or high MIB-1 expressions: HR 1.89, 95% CI 1.16 to 3.08, P = .010 and HR 2.20, 95% CI 1.36 to 3.54, P = .001, respectively. CONCLUSIONS: Very high Ang-2 expression was associated with better survival in patients with RCC. Ang-2 expression correlated with tumor stage and grade, but it was still an independent prognostic factor in a multivariate analysis. PMID- 27554587 TI - Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment? AB - Sepsis is the most frequent cause of death in noncoronary intensive care units. In the past 10 years, progress has been made in the early identification of septic patients and their treatment. These improvements in support and therapy mean that mortality is gradually decreasing, however, the rate of death from sepsis remains unacceptably high. Immunotherapy is not currently part of the routine treatment of sepsis. Despite experimental successes, the administration of agents to block the effect of sepsis mediators failed to show evidence for improved outcome in a multitude of clinical trials. The following survey summarizes the current knowledge and results of clinical trials on the immunotherapy of sepsis and describes the limitations of our knowledge of the pathogenesis of sepsis. Administration of immunomodulatory drugs should be linked to the current immune status assessed by both clinical and molecular patterns. Thus, a careful daily review of the patient's immune status needs to be introduced into routine clinical practice giving the opportunity for effective and tailored use of immunomodulatory therapy. PMID- 27554588 TI - Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma. AB - PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability, treatment, and prognosis in patients with lung adenocarcinoma. A total of 810 patients with completely resected lung adenocarcinoma were recruited between 2008 and 2013. The status of PIK3CA mutation and other three genes, that is, EGFR mutation, KRAS mutation and ALK fusion were examined by reverse transcription-polymerase chain reaction (RT-PCR). Survival curves were plotted with the Kaplan-Meier method and log-rank for comparison. Cox proportional hazard model was performed for multivariate analysis. Among the 810 patients, 23 cases of PIK3CA mutation were identified with a frequency of 2.8%. There were 14 men and 9 women with a median age of 61 years. Seventeen tumors revealed concurrent gene abnormalities of EGFR mutation (n = 12), KRAS mutation (n = 3), and ALK fusion (n = 2). Seven patients with EGFR & PIK3CA mutations recurred and administrated of EGFR-TKIs yielded a median progression free-survival of 6.0 months. Among four eviromous-treated patients, stable disease was observed in three patients with a median Progression free survival (PFS) of 3.5 months. Patients with and without PIK3CA mutation had different overall survivals (32.2 vs. 49.6 months, P = 0.003). Multivariate analysis revealed that PIK3CA mutation was an independent predictor of poor overall survival (HR = 2.37, P = 0.017). The frequency of PIK3CA mutation was around 2.8% in the Chinese patients of lung adenocarcinoma. PIK3CA mutation was associated with reduced PFS of EGFR-TKIs treatment and shorter overall survival. PMID- 27554589 TI - Functional Diversification of the Four MARCKS Family Members in Zebrafish Neural Development. AB - Myristoylated alanin-rich C-kinase substrate (MARCKS) and MARCKS-like 1, each encoded by a different gene, comprise a very small family of actin-modulating proteins with essential roles in mammalian neural development. We show here that four genes (two marcks and two marcksl1) are present in teleosts including zebrafish, while ancient actinopterigians, sarcopterigian fishes, and chondrichtyans only have two. No marcks genes were found in agnaths or invertebrates. All four zebrafish genes are expressed during development, and we show here how their early knockdown causes defects in neural development, with some phenotypical differences. Knockdown of marcksa generated embryos with smaller brain and eyes, while marcksb caused different morphogenetic defects, such as larger hindbrain ventricle and folded retina. marcksl1a and marcksl1b morpholinos also caused smaller eyes and brain, although marcksl1a alone generated larger brain ventricles. At 24 hpf, marcksb caused a wider angle of the hindbrain walls, while marcksl1a showed a "T-shaped" neural tube and alterations in neuroepithelium organization. The double knockdown surprisingly produced new features, which included an increased neuroepithelial disorganization and partial neural tube duplications evident at 48 hpf, suggesting defects in convergent extension. This disorganization was also evident in the retina, although retinal ganglion cells were still able to differentiate. marcksl1b morphants presented a unique retinal phenotype characterized by the occurrence of sporadic ectopic neuronal differentiation. Although only marcksl1a morphant had a clear "ciliary phenotype," all presented significantly shorter cilia. Altogether, our data show that all marcks genes have functions in zebrafish neural development, with some differences that suggest the onset of protein diversification. PMID- 27554590 TI - Cloning and characterization of novel cyclotides genes from South American plants. AB - Cyclotides are multifunctional plant cyclic peptides containing 28-37 amino acid residues and a pattern of three disulfide bridges, forming a motif known as the cyclic cystine knot. Due to their high biotechnological potential, the sequencing and characterization of cyclotide genes are crucial not only for cloning and establishing heterologous expression strategies, but also to understand local plant evolution in the context of host-pathogen relationships. Here, two species from the Brazilian Cerrado, Palicourea rigida (Rubiaceae) and Pombalia lanata (A.St.-Hil.) Paula-Souza (Violaceae), were used for cloning and characterizing novel cyclotide genes. Using 3' and 5' RACE PCR and sequencing, two full cDNAs, named parigidin-br2 (P. rigida) and hyla-br1 (P. lanata), were isolated and shown to have similar genetic structures to other cyclotides. Both contained the conserved ER-signal domain, N-terminal prodomain, mature cyclotide domain and a C terminal region. Genomic sequencing of parigidin-br2 revealed two different gene copies: one intronless allele and one presenting a rare 131-bp intron. In contrast, genomic sequencing of hyla-br1 revealed an intronless gene-a common characteristic of members of the Violaceae family. Parigidin-br2 5' and 3' UTRs showed the presence of 12 putative candidate sites for binding of regulatory proteins, suggesting that the flanking and intronic regions of the parigidin-br2 gene must play important roles in transcriptional rates and in the regulation of temporal and spatial gene expression. The high degree of genetic similarity and structural organization among the cyclotide genes isolated in the present study from the Brazilian Cerrado and other well-characterized plant cyclotides may contribute to a better understanding of cyclotide evolution. PMID- 27554591 TI - Comparison of second transplantation and donor lymphocyte infusion for donor mixed chimerism after allogeneic stem cell transplantation for nonmalignant diseases. AB - BACKGROUND: Donor mixed chimerism (MC) is an increasing problem after hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases. PROCEDURE: In this study, a self-administered questionnaire was used to retrospectively compare efficacy and safety in 49 patients undergoing second HSCT (n = 13) or donor lymphocyte infusion (DLI; n = 36) as treatment for MC. RESULTS: The response rate to DLI of patients with secondary graft failure (GF) (25.0%) was significantly lower than that of patients without secondary GF (81.3%; P = 0.041). Among patients undergoing DLI, the rates of successful response were significantly higher in patients having at least 30% donor chimerism (94.1%) than in patients having less than 30% donor chimerism (61.1%; P = 0.041). Furthermore, the rates of successful response were significantly higher in patients receiving larger first or maximum doses of DLI. Sixteen (50.0%) of 32 patients without secondary GF attained complete chimerism after DLI. The cumulative incidence of grade II-IV acute graft-versus-host disease and cytopenia was 37.6 and 26.1%, respectively. CONCLUSIONS: DLI yields promising response rates in most patients with higher donor chimerism levels, whereas second HSCT is more likely to benefit patients with lower donor chimerism levels. PMID- 27554593 TI - [18F]FDG-PET Combined with MRI Elucidates the Pathophysiology of Traumatic Brain Injury in Rats. AB - Non-invasive measurements of brain metabolism using 18F-fluorodeoxyglucose (FDG) with positron emission tomography (PET) may provide important information about injury severity following traumatic brain injury (TBI). There is growing interest in the potential of combining functional PET imaging with anatomical and functional magnetic resonance imaging (MRI). This study aimed to investigate the effectiveness of combining clinically available FDG-PET with T2 and diffusion MR imaging, with a particular focus on inflammation and the influence of glial alterations after injury. Adult male Sprague Dawley rats underwent a moderate controlled cortical impact (CCI) injury followed by FDG-PET, MRI, and histological evaluation. FDG uptake showed significant alterations in the corpus callosum, hippocampus, and amygdala after TBI, demonstrating that a relatively "focal" CCI injury can result in global alterations. Analysis of MRI T2 intensity and apparent diffusion coefficient (ADC) also showed significant alterations in these regions to include cytotoxic and vasogenic edema. Histology showed increased glial activation in the corpus callosum and hippocampus that was associated with increased FDG uptake at sub-acute time-points. Glial activation was not detected in the amygdala but neuronal damage was evident, as the amygdala was the only region to show a reduction in both FDG uptake and ADC at sub-acute time-points. Overall, FDG-PET detected glial activation but was confounded by the presence of cell damage, whereas MRI consistently detected cell damage but was confounded by glial activation. These results demonstrate that FDG-PET and MRI can be used together to improve our understanding of the complex alterations in the brain after TBI. PMID- 27554592 TI - Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals. AB - In mammals it is unclear if UHRF1-mediated DNA maintenance methylation by DNMT1 is strictly dependent on histone H3K9 methylation. Here we have generated an Uhrf1 knockin (KI) mouse model that specifically abolishes the H3K9me2/3-binding activity of Uhrf1. The homozygous Uhrf1 KI mice are viable and fertile, and exhibit ~10% reduction of DNA methylation in various tissues. The reduced DNA methylation occurs globally in the genome and does not restrict only to the H3K9me2/3 enriched repetitive sequences. In vitro UHRF1 binds with higher affinity to reconstituted nucleosome with hemi-methylated CpGs than that with H3K9me2/3, although it binds cooperatively to nucleosome with both modifications. We also show that the nucleosome positioning affects the binding of methylated DNA by UHRF1. Thus, while our study supports a role for H3K9 methylation in promoting DNA methylation, it demonstrates for the first time that DNA maintenance methylation in mammals is largely independent of H3K9 methylation. PMID- 27554594 TI - Carotid intima-media thickness in young survivors of childhood cancer. AB - INTRODUCTION: Radiotherapy (RT) and some chemotherapy regimens are known risk factors predisposing to the development of premature arterial disease. Vascular ultrasound measurement of carotid intima-media thickness (IMT) is a non-invasive technique, useful to detect early subclinical symptoms of atherosclerosis that can appear in the paediatric population. We analysed the influence of chemotherapy and moderate doses of head or neck irradiation in childhood cancer survivors on the possibility of premature carotid artery disease. METHODS: Ultrasound measurements of the intima-media thickness (IMT) in the common carotid artery (CCA), bulb and internal carotid artery (ICA) were performed in 74 young cancer survivors and in 48 age- and sex-matched controls. RESULTS: In the whole study group, we observed higher IMT in all positions as compared with the control, except for comparable thickness in the CCA (bilaterally). We failed to find any differences in IMT between irradiated and non-irradiated females. In irradiated males, all IMT measurements on the right side were higher than in non irradiated patients. There was no effect of body mass index, blood pressure, serum cholesterol, triglycerides, fibrinogen and thyroid hormones on IMT. In the irradiated group, a positive correlation was observed between IMT in the right bulb and the post-radiation time. CONCLUSIONS: Anticancer treatment during childhood, especially including irradiation to the mediastinum, head or neck, affects the IMT, particularly in males. This suggests a possible role of irradiation in the premature development of carotid artery disease. PMID- 27554595 TI - Lubricity of gold nanocrystals on graphene measured using quartz crystal microbalance. AB - In order to test recently predicted ballistic nanofriction (ultra-low drag and enhanced lubricity) of gold nanocrystals on graphite at high surface speeds, we use the quartz microbalance technique to measure the impact of deposition of gold nanocrystals on graphene. We analyze our measurements of changes in frequency and dissipation induced by nanocrystals using a framework developed for friction of adatoms on various surfaces. We find the lubricity of gold nanocrystals on graphene to be even higher than that predicted for the ballistic nanofriction, confirming the enhanced lubricity predicted at high surface speeds. Our complementary molecular dynamics simulations indicate that such high lubricity is due to the interaction strength between gold nanocrystals and graphene being lower than previously assumed for gold nanocrystals and graphite. PMID- 27554596 TI - Increase in antioxidant activity by sheep/goat whey protein through nuclear factor-like 2 (Nrf2) is cell type dependent. AB - The aim of the present study was to investigate the molecular mechanisms through which sheep/goat whey protein exerts its antioxidant activity. Thus, it was examined whey protein's effects on the expression of transcription factor, nuclear factor-like 2 (Nrf2) and on the expression and activity of a number of antioxidant and phase II enzymes, superoxide dismutase (SOD), catalase (CAT), heme oxygenase 1 (HO-1), synthase glutamyl cysteine (GCS) and glutathione-s transferase (GST), in muscle C2C12 and EA.hy926 endothelial cells. C2C12 and EA.hy926 cells were treated with sheep/goat whey protein (0.78 and 3.12 mg/ml) and incubated for 3, 6, 12, 18 and 24 h. Whey protein increased significantly the expression of Nrf2 only in EA.hy926 cells. Also, the expression of SOD, HO-1, CAT and the activity of SOD, CAT and GST were increased significantly in both cells types. The expression of GCS was increased significantly only in C2C12 cells. Sheep/goat whey protein was shown for the first time to exert its antioxidant activity through Nrf2-dependent mechanism in endothelial cells and Nrf2 independent mechanism in muscle cells. Thus, Nrf2 could be a target for food supplements containing whey protein in order to prevent oxidative stress damages and diseases related to endothelium. PMID- 27554597 TI - In vitro genotoxicity testing-Can the performance be enhanced? AB - The assessment of genotoxicity represents an essential component of the safety assessment of all types of substances. Several in vitro tests are available at different stages of development and acceptance, yet they are not considered at present sufficient to fully replace animal tests needed to evaluate the safety of substances. For an overall improvement of the traditional genotoxicity testing paradigm, several recent activities have taken place. These include the improvement of existing tests, the development of novel tests, as well as, the establishment and exploration of approaches to optimise in vitro testing accuracy. Furthermore, useful tools, such as databases or reference chemical lists have been developed to support advances in this field. PMID- 27554599 TI - Fostering Emotion Expression and Affective Involvement with Communication Partners in People with Congenital Deafblindness and Intellectual Disabilities. AB - BACKGROUND: Recent studies have shown that it is possible to foster affective involvement between people with congenital deafblindness and their communication partners. Affective involvement is crucial for well-being, and it is important to know whether it can also be fostered with people who have congenital deafblindness and intellectual disabilities. METHODS: This study used a multiple baseline design to examine whether an intervention based on the Intervention Model for Affective Involvement would (i) increase affective involvement between four participants with congenital deafblindness and intellectual disabilities and their 13 communication partners and (ii) increase the participants' positive emotions and decrease their negative emotions. RESULTS: In all cases, dyadic affective involvement increased, the participants' very positive emotions also increased and the participants' negative emotions decreased. CONCLUSION: The results indicate that communication partners of persons with congenital deafblindness and intellectual disabilities can be successfully trained to foster affective involvement. PMID- 27554598 TI - Short-term culture of monocytes as an in vitro evaluation system for bionanomaterials designated for medical use. AB - We studied the feasibility of using a short-term culture of monocytes, isolated from peripheral donor blood, to assess the biological activity of different types of bionanomaterials (BNM): biodegradable polimeric particles, fiber and film substrates of micro- and nano-dimensions, fullerenes (F) and nanodiamonds (ND), which are either currently in use and/or potentially applicable in medicine. Additionally, the effect of creating a protein corona on ND and F particles was investigated. The cellular reduction of (4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) is a well-established tool for assessing the viability/metabolic activity of cells. The scanning electron microscopy assay can detect fine changes in cell morphology. In the present study BNM have been shown to affect; in a size, chemical composition and morphological characteristics dependent manner, the ability of monocytes to reduce MTT as well as their morphology. Moreover, the specific effects of ND and F on MTT reduction and cell morphology were exhibited in a dose-dependent manner and sensitive to the formation of surface protein corona. Our results suggest that short-term culture of monocytes is a sensitive model system for assessing the biological effects of BMPs in vitro. PMID- 27554600 TI - Development of Light-Activated CRISPR Using Guide RNAs with Photocleavable Protectors. AB - The ability to remotely trigger CRISPR/Cas9 activity would enable new strategies to study cellular events with greater precision and complexity. In this work, we have developed a method to photocage the activity of the guide RNA called "CRISPR plus" (CRISPR-precise light-mediated unveiling of sgRNAs). The photoactivation capability of our CRISPR-plus method is compatible with the simultaneous targeting of multiple DNA sequences and supports numerous modifications that can enable guide RNA labeling for use in imaging and mechanistic investigations. PMID- 27554601 TI - 14-3-3zeta promotes lung cancer cell invasion by increasing the Snail protein expression through atypical protein kinase C (aPKC)/NF-kappaB signaling. AB - 14-3-3zeta has been identified as a putative oncogene in several cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms underlying its functions remain undefined. In this study, we show that overexpression of 14 3-3zeta was frequently detected in lung adenocarcinoma (LuAC) tissues and was significantly associated with lymph node metastasis and poor outcome. Functional studies demonstrated that 14-3-3zeta promoted migration and invasion in A549 cells, both of which were effectively inhibited when 14-3-3zeta was silenced with short hairpin RNA (shRNA). Furthermore, 14-3-3zeta-mediated invasion of cancer cells was found to upregulate Snail through the activation of atypical protein kinase C (aPKC). Activation of aPKCzeta mediates this effect by stimulating NF kappaB signaling. Our results identify a specific pathway by which 14-3-3zeta induces tumor invasion and provide insight into potential therapeutic approaches to target 14-3-3zeta-associated lung adenocarcinoma. PMID- 27554602 TI - Characterization of a spontaneously generated murine retinal pigmented epithelium cell line; a model for in vitro experiments. AB - Retinal pigmented epithelium (RPE), the outermost layer of the retina, has a key role in maintaining retinal cells' functions. Severity of the culture of RPE cells has exerted many limitations to both in vitro and in vivo studies and its therapeutic applications. Therefore, establishment of RPE cell lines with high proliferative potential can considerably improve study of RPE cell biology. Here we report generation of a spontaneously immortalized murine RPE cell line in primary mouse RPE cell culture. Founded colonized cells were picked up and expression of RPE and retinal progenitor cells' (RPC) markers were studied using immunocytochemistry (ICC). Emerged cells cultured over 35 passages and population doubling times in different serum concentrations were calculated. We also investigated the ability of cells for becoming transfected by calcium-phosphate method and for becoming infected by adeno-associated virus serotype 2 (AAV2) using flow cytometry. Data showed that the cobblestone constituent cells expressed RPE65, cytokeratin and ZO1 and moreover several progenitor markers such as Pax6, Sox2, Nestin and Chx10. It revealed that, despite primary RPE cells, the newly emerged cells were easily transfectable and were highly infectable when compared with HEK293T cells. Our data indicated that the emerged mouse RPE cell line pretended RPC-like phenotype and also simultaneously expressed RPE markers. It would be a promising model for leading studies on RPE and RPC cells and substantially confirmed the great RPE plasticity and its invaluable potential in research studies. PMID- 27554603 TI - Metformin activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against Amyloid-beta-induced mitochondrial dysfunction. AB - Alzheimer's disease (AD) is the general consequence of dementia and is diagnostic neuropathology by the cumulation of amyloid-beta (Abeta) protein aggregates, which are thought to promote mitochondrial dysfunction processes leading to neurodegeneration. AMP-activated protein kinase (AMPK), a critical regulator of energy homeostasis and a major player in lipid and glucose metabolism, is potentially implied in the mitochondrial deficiency of AD. Metformin, one of the widespread used anti- metabolic disease drugs, use its actions in part by stimulation of AMPK. While the mechanisms of AD are well established, the neuronal roles for AMPK in AD are still not well understood. In the present study, human neural stem cells (hNSCs) exposed to Abeta had significantly reduced cell viability, which correlated with decreased AMPK, neuroprotective genes (Bcl 2 and CREB) and mitochondria associated genes (PGC1alpha, NRF-1 and Tfam) expressions, as well as increased activation of caspase 3/9 activity and cytosolic cytochrome c. Co-treatment with metformin distinct abolished the Abeta caused actions in hNSCs. Metformin also significantly rescued hNSCs from Abeta mediated mitochondrial deficiency (lower D-loop level, mitochondrial mass, maximal respiratory function, COX activity, and mitochondrial membrane potential). Importantly, co-treatment with metformin significantly restored fragmented mitochondria to almost normal morphology in the hNSCs with Abeta. These findings extend our understanding of the central role of AMPK in Abeta related neuronal impairment. Thus, a better understanding of AMPK might assist in both the recognition of its critical effects and the implementation of new therapeutic strategies in the treatment of AD. PMID- 27554604 TI - Variation in helper effort among cooperatively breeding bird species is consistent with Hamilton's Rule. AB - Investment by helpers in cooperative breeding systems is extremely variable among species, but this variation is currently unexplained. Inclusive fitness theory predicts that, all else being equal, cooperative investment should correlate positively with the relatedness of helpers to the recipients of their care. We test this prediction in a comparative analysis of helper investment in 36 cooperatively breeding bird species. We show that species-specific helper contributions to cooperative brood care increase as the mean relatedness between helpers and recipients increases. Helper contributions are also related to the sex ratio of helpers, but neither group size nor the proportion of nests with helpers influence helper effort. Our findings support the hypothesis that variation in helping behaviour among cooperatively breeding birds is consistent with Hamilton's rule, indicating a key role for kin selection in the evolution of cooperative investment in social birds. PMID- 27554607 TI - The role of peer support in ICU rehabilitation. PMID- 27554605 TI - Investigating the nature of co-occurring depression and anxiety: Comparing diagnostic and dimensional research approaches. AB - BACKGROUND: Although approximately half of adults diagnosed with a depressive or anxiety disorder exhibit their simultaneous co-occurrence, traditional research has centered on single-target diagnoses, overlooking comorbidities within samples. In this article, we review and extend the literature that directly investigates co-occurring depression and anxiety, with the goal of shifting the focus from co-occurring diagnoses to symptom dimensions. METHODS: First, we review studies that have directly compared psychobiological features (neural, neuroendocrine, autonomic) across depression, anxiety, and their co-occurrence, defined either categorically or dimensionally. Second, we analyze adults' diurnal cortisol secretion to examine the independent and interactive relations of continuously-assessed depressive and anxiety symptoms to neuroendocrine function. RESULTS: Previous findings on the psychobiology of diagnostic co-occurrence are mixed. While nascent, evidence from dimensionally focused studies suggests that co-occurring levels of depressive and anxiety symptoms can interact with one another, as reflected in a distinct psychobiological profile for individuals with high levels of both symptom dimensions. Results of our analyses support this formulation: we found that depressive and anxiety symptom dimensions interacted consistently in their relation to the measures of diurnal cortisol. LIMITATIONS: The illustrative sample was relatively small and included only women; future research should examine generalizability of these findings. CONCLUSIONS: A dimensional approach to investigating the psychobiology of co-occurring depression and anxiety affords both conceptual and practical advantages. Simultaneously assessing depressive and anxiety symptom dimensions can efficiently capture their unique, shared, and interactive features, thereby identifying targets for intervention across a wide range of symptom presentations. PMID- 27554608 TI - Intensive care nurses' knowledge of enteral nutrition: A descriptive questionnaire. AB - BACKGROUND: Nurses have an important role in the delivery and management of enteral nutrition in critically ill patients, to prevent iatrogenic malnutrition. It is not clear how nurses source enteral nutrition information. OBJECTIVE: This study aimed to explore Australian nurses' enteral nutrition knowledge and sources of information. DESIGN: Data were collected from members of the Australian College of Critical Care Nurses in May 2014 using an online questionnaire. A combination of descriptive statistics and non-parametric analyses were undertaken to evaluate quantitative data. Content analysis was used to evaluate qualitative data. RESULTS: 359 responses were included in data analysis. All respondents were Registered Nurses with experience working in an Australian intensive care unit or high dependency unit. Most respondents reported their enteral nutrition knowledge was good (n=205, 60.1%) or excellent (n=35, 10.3%), but many lacked knowledge regarding the effect of malnutrition on patient outcomes. Dietitians and hospital protocols were the most valuable sources of enteral nutrition information, but were not consistently utilised. CONCLUSION: Significant knowledge deficits in relation to enteral nutrition were identified. Dietitians were the preferred source of nurses' enteral nutrition information, however their limited availability impacted their efficacy as an information resource. Educational opportunities for nurses need to be improved to enable appropriate nutritional care in critically ill patients. PMID- 27554610 TI - Unfurling the Genetic Map of Sarcomas. AB - An international team of researchers has uncovered multiple new germline mutations that may influence the development of sarcomas. Notably, they found that variants in several DNA damage sensing and repair genes contribute greatly to sarcoma risk, including BRCA2, ATM, ATR, and ERCC2. PMID- 27554609 TI - Rotator cuff repair: a review of surgical techniques, animal models, and new technologies under development. AB - Rotator cuff tears are the most common musculoskeletal injury occurring in the shoulder. Current surgical repair fails to heal in 20% to 95% of patients, depending on age, size of the tear, smoking, time of repair, tendon quality, muscle quality, healing response, and surgical treatments. These problems are worsened by the limited healing potential of injured tendons attributed to the presence of degenerative changes and relatively poor vascularity of the cuff tendons. Development of new techniques to treat rotator cuff tears requires testing in animal models to assess safety and efficacy before clinical testing. Hence, it is important to evaluate appropriate animal models for rotator cuff research with degeneration of tendons, muscular atrophy, and fatty infiltration similar to humans. This report reviews current clinical treatments and preclinical approaches for rotator cuff tear repair. The review will focus on current clinical surgical treatments, new repair strategies under clinical and preclinical development, and will also describe different animal models available for rotator cuff research. These findings and future directions for rotator cuff tear repair will be discussed. PMID- 27554606 TI - Disruptive Mood Dysregulation Disorder (DMDD): An RDoC perspective. AB - In recent years, there has been much debate regarding the most appropriate diagnostic classification of children exhibiting emotion dysregulation in the form of irritability and severe temper outbursts. Most recently, this has resulted in the addition of a new diagnosis, Disruptive Mood Dysregulation Disorder (DMDD) in the DSM 5. The impetus for including this new disorder was to reduce the number of diagnoses that these children would typically receive; however, there is concern that it has only complicated matters rather than simplifying them. For example, a recent epidemiologic study shows that DMDD cannot be differentiated from oppositional defiant disorder (ODD) based on symptoms alone. Thus, these children are an ideal population in which to apply RDoC constructs in order to obtain greater clarity in terms of underlying processes and ultimately, inform nosology and appropriate interventions. The aim of this article is to provide a foundation for future research by examining extant theoretical and empirical evidence for the role of four key RDoC constructs in DMDD. PMID- 27554611 TI - Illuminating T-cell Exhaustion. AB - Two studies have illuminated some of the molecular underpinnings of T-cell exhaustion. The first pinpoints the subset of exhausted T cells that revive upon PD-1 blockade. The second describes key metabolic deficiencies-restricted glucose uptake and mitochondrial dysfunction-that drive T cells to exhaustion. PMID- 27554612 TI - Vemurafenib Active in Iodine-Refractory Thyroid Cancer. AB - A new study shows that the BRAF inhibitor vemurafenib may induce partial responses and stable disease in patients with papillary thyroid cancer that has become refractory to radioactive iodine. However, the drug led to a variety of serious adverse events in roughly 65% of patients, including the development of some squamous cell carcinomas. PMID- 27554613 TI - Jackson Lab Receives New KOMP2 Grant. AB - The Jackson Laboratory has been awarded $28.3 million from the NIH to expand the Knockout Mouse Production and Phenotyping Project, which was launched in 2011. Since then, researchers there have made and extensively phenotyped 833 knockout mouse strains from embryonic stem cells. Now, they'll capitalize on CRISPR/Cas9 technology to generate another 1,000 strains in the next 5 years. PMID- 27554614 TI - Evaluation of the types and frequency of drug-related problems and the association with gender in patients with chronic diseases attending a primary health care center in Jordan. AB - BACKGROUND: Drug-related problems (DRPs) can be defined as any event that is drug related that results in harm or in providing less than optimum medical care to patients. The aim of this study is to determine the types and frequency of each type of DRP in selected outpatient settings in Jordan, with emphasis on gender as a grouping variable. METHODS: This study was a non-randomized controlled trial, carried out over 3 days, at Alsarih Medical Health Center in the north of Jordan. Clinical pharmacists conducting the research interviewed a randomly selected population, assessed their DRPs, proposed appropriate clinical interventions to physicians and provided appropriate patient counseling. RESULTS: The study included a total of 258 patients (mean age 54.4+/-12.1; male ratio 37.6%). The most frequently encountered DRPs in our study were patients' need for counseling and education (83.8%), and life style modifications (80%). This study also revealed that 71.8% of patients required additional and/or more frequent monitoring, and 53% of patients had untreated conditions that required pharmacological and/or non-pharmacological interventions. Gender did not affect the frequency of DRPs among patients. CONCLUSION: Certain types of DRPs are the most common among outpatient settings. Therefore, measures should be taken to specifically tackle these types of DRPs. PMID- 27554615 TI - Percutaneous laser ablation for treatment of locally recurrent papillary thyroid carcinoma <15 mm. AB - AIM: To evaluate the efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for recurrent papillary thyroid carcinomas (PTC) <15 mm in the neck. MATERIALS AND METHODS: A retrospective study was conducted in 21 patients with 27 recurrent PTC lesions who underwent PLA. The extent of ablation was assessed by contrast-enhanced ultrasonography (CEUS) after PLA. Measurement of the volume of tumour and serum thyroglobulin, and clinical evaluation were performed at 7 days, and 1, 3, 6, and 12 months, and every 6 months thereafter. RESULTS: The procedure was well tolerated. Of 21 patients, 18 were successfully treated in a single session. Incomplete ablation was detected by CEUS in three patients, and a second ablation was performed. The mean largest diameter and the average baseline volume were reduced from 7.5+/-2.8 mm and 105.4+/-114 mm3 to 0.4+/-1 mm and 0.8+/-2.4 mm3 at the final follow-up. CONCLUSIONS: Ultrasound guided PLA is effective for the treatment of recurrent PTCs with a comparable success rate to radio-iodine therapy, and it may become a primary choice of treatment for recurrent PTCs in selected patients who are ineligible for surgery and/or prefer not to have further surgery. PMID- 27554616 TI - Does perfusion CT play a role in the evaluation of percutaneous microwave-ablated lung tumours? AB - AIM: To assess the clinical utility of perfusion computed tomography (pCT) parameters in microwave ablation (MWA) of lung tumours. MATERIALS AND METHODS: Patients were included who had primary or metastatic lung tumours and underwent pCT studies immediately pre- and post-MWA. Perfusion maps of the tumours were constructed using CT perfusion software (GE, Milwaukee, WI, USA). Regions of interest were drawn on sequential axial sections to extract the pCT parameters, blood volume (BV), average blood flow (BF), and mean transit time (MTT) from the entire tumour volume. Direct visualisation of perfusion maps were performed by two experienced readers blinded to outcome. Data were analysed using the Mann Whitney test. RESULTS: Thirty-one patients with 34 lung tumours had follow-up data at 12 months. The median tumour diameter was 19 mm (10-52 mm). Seven patients developed local tumour progression (LTP) at 12 months. There was no statistical difference between patients with LTP and complete treatment based on quantitative pCT parameters. Using radiologist visualisation of perfusion maps, there was moderate agreement between the two readers (kappa coefficient 0.53) with a combined 96% sensitivity, 62% specificity, 91% positive predictive value, and 80% negative predictive value. CONCLUSION: Quantitative pCT parameters do not help differentiate between LTP and complete treatment, but subjective analysis of perfusion maps may be a useful assessment tool for identifying treatment adequacy potentially enabling identification of areas requiring further treatment at the time of the procedure. PMID- 27554617 TI - MRI and clinicopathological correlation of childhood primary central nervous system angiitis. AB - AIM: To review the long-term clinical and imaging follow-up of eight children with histopathologically proven childhood primary central nervous system angiitis (cPACNS). MATERIALS AND METHODS: Eight children (5-17 years, five female and three male patients) with biopsy-proven cPACNS vasculitis were reviewed retrospectively. All children were followed at the Children's Hospital of Eastern Ontario. Magnetic resonance imaging (MRI) images of the brain parenchyma and vessel pattern of the arteries of the circle of Willis were reviewed at baseline and follow-up(s). All MRI images were correlated with clinical and histopathological findings. RESULTS: Seven (87.5%) children demonstrated parenchymal abnormalities: five of the seven (71.4%) presented with non haemorrhagic lesions, one (14.3%) presented with a parenchymal bleed, and one (14.3%) showed diffuse oedema. One child remained negative for brain parenchymal abnormality at baseline and follow-up. Of the seven children with a parenchymal abnormality, parenchymal enhancement was seen in two (28.5%) and leptomeningeal enhancement was seen in one child. Only two children had positive diffusion weighted imaging (DWI) restriction at baseline. Five of the seven children (71.4%) showed no magnetic resonance angiography (MRA) abnormalities at baseline. In one, MRA detected complete absence of flow. Follow-up MRA (24-74 months) demonstrated that five of the seven (71.4%) children had progressive paucity of the peripheral vascularity. Two children (28.5%) with shorter-term follow-up (7 and 13 months) did not demonstrate MRA changes. CONCLUSION: Long-term follow-up MRA demonstrated progressive paucity of peripheral vessels, which could be secondary to the inflammation affecting the peripheral vasculature causing reduction in vessel lumen size beyond the resolution of the maximum intensity projection (MIP) reconstruction. PMID- 27554618 TI - Prospective prediction of the major component of urinary stone composition with dual-source dual-energy CT in vivo. AB - AIM: To prospectively evaluate the diagnostic accuracy of dual-source dual-energy computed tomography (DSDECT) for predicting the major component and determining the composition of urinary calculi in patients with urolithiasis, using postoperative in vitro Fourier transform infrared spectroscopy (FT-IR) analysis as the reference standard. MATERIALS AND METHODS: Patients with known urolithiasis underwent preoperative DSDECT evaluation, and subsequently, underwent surgical removal of the stones. All patients were examined using the dual-energy renal stone protocol. Material-specific chromatic images were made using dedicated post-processing software. The final determination of stone composition was made using FT-IR postoperatively. Diagnostic parameters of DSDECT for predicting the major component and detecting the presence of four composition types were calculated. RESULTS: A total of 81 urinary calculi were included in this study. Forty-three were pure stones and 38 were mixed stones according to FT IR. DSDECT correctly identified the major component of all pure stones and 36 mixed stones. The major component of two mixed stones with uric acid as the major component was falsely interpreted as calcium oxalate. The overall accuracy of DSDECT for predicting the major component of stones was 97.5% (79/81). The accuracy of DSDECT for detecting the presence of four types of composition, uric acid, cysteine, hydroxyapatite, and calcium oxalate, was 97.5% (79/81), 93.8% (76/81), 80.2% (65/81), and 93.8% (76/81), respectively. CONCLUSION: DSDECT could accurately predict the major component of urinary calculi and detect uric acid, cysteine, and calcium oxalate with a satisfactory accuracy. PMID- 27554620 TI - Association of HLA genotypes with phenobarbital hypersensitivity in children. AB - OBJECTIVE: Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. METHODS: The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. RESULTS: The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15 661.62). SIGNIFICANCE: An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children. PMID- 27554619 TI - A Novel High-Throughput Screening Platform Reveals an Optimized Cytokine Formulation for Human Hematopoietic Progenitor Cell Expansion. AB - The main limitations of hematopoietic cord blood (CB) transplantation, viz, low cell dosage and delayed reconstitution, can be overcome by ex vivo expansion. CB expansion under conventional culture causes rapid cell differentiation and depletion of hematopoietic stem and progenitor cells (HSPCs) responsible for engraftment. In this study, we use combinatorial cell culture technology (CombiCult(r)) to identify medium formulations that promote CD133+ CB HSPC proliferation while maintaining their phenotypic characteristics. We employed second-generation CombiCult screens that use electrospraying technology to encapsulate CB cells in alginate beads. Our results suggest that not only the combination but also the order of addition of individual components has a profound influence on expansion of specific HSPC populations. Top protocols identified by the CombiCult screen were used to culture human CD133+ CB HSPCs on nanofiber scaffolds and validate the expansion of the phenotypically defined CD34+CD38lo/-CD45RA-CD90+CD49f+ population of hematopoietic stem cells and their differentiation into defined progeny. PMID- 27554621 TI - Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens. AB - Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4(+)T/CD8(+)T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections. PMID- 27554622 TI - The role of extended criteria donors in liver transplantation for nonalcoholic steatohepatitis. AB - BACKGROUND: Nonalcoholic steatohepatitis is expected to become the leading indication for liver transplantation. Use of extended criteria donors (ECD) may help with donor allocation in these patients. The objective of this study was to determine the use of ECDs in patients with nonalcoholic steatohepatitis undergoing liver transplantation to stimulate a liver-specific predictive model for ECD use. METHODS: The United Network for Organ Sharing database was used to identify patients undergoing liver transplantation for nonalcoholic steatohepatitis (2002-2014). Cox hazards models were created using (1) United Network for Organ Sharing ECD criteria (based on kidney allocation), (2) individual donor characteristics (age, sex, race, cause of death, body mass index, cold ischemic time), and (3) the Kidney Donor Profile Index (KDPI) to examine the effect of ECDs on mortality and graft failure. RESULTS: A total of 4,387 patients underwent liver transplantation for nonalcoholic steatohepatitis; 1,359 (30.9%) patients received an ECD. Transplantation with ECD livers had comparable patient survival (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.91-1.23) between donor types but an increased risk of graft failure (HR 1.18, 95% CI 1.03-1.36) compared to standard donors. Individual characteristics did not affect patient survival or graft failure. A 10% increase in KDPI was associated with a 28% increase in patient mortality (HR 1.28, 95% CI 1.02-1.60) and 45% increase in graft failure (HR 1.45, 95% CI 1.18-1.80). CONCLUSION: Based on the current United Network for Organ Sharing definition, ECDs in nonalcoholic steatohepatitis were associated with similar overall survival but increased risk of graft failure. Given the shortage of organs, creation of an easily calculated, liver-specific model similar to the KDPI may help risk stratify patients and improve organ allocation. PMID- 27554623 TI - Variation in inpatient hospital and physician payments among patients undergoing general versus orthopedic operations. AB - BACKGROUND: Comparative data on surgeon payments for operative procedures are not well documented. We sought to assess variations in surgeon payments after common general and orthopedic operations using a nationally representative sample of privately insured patients. METHODS: A total of 486,506 patients who underwent a general (appendectomy, cholecystectomy, colectomy) or orthopedic (total knee replacement, total hip replacement) operation between 2010-2012 were identified from the Truven Health MarketScan database. RESULTS: Median age was 54 years (general operation, 44 years vs orthopedic operation, 58 years; P < .001). Patients had an average Charlson Comorbidity Index of 0 (interquartile range [IQR]: 0, 1). Median duration of stay was 3 days (IQR: 2, 4) (general operation, 3 days [IQR: 1, 5] vs orthopedic operation, 3 days [IQR: 2, 3]; P < .001). Total hospital payments averaged $18,209 (IQR: $11,751, $26,598) (general operation: $12,744 [IQR: $8,402, $19,896] vs orthopedic operation: $22,386 [IQR: $16,888, $30,100]; P < .001). Median surgeon reimbursement was $1,923 (IQR: $1,146, $2,676), with orthopedic surgeon payments being on average twice as high as general surgeon payments ($2,349 vs $1,191; P < .001). Median surgeon payment varied among both general (appendectomy: $903 vs cholecystectomy: $1,125 vs colectomy: $2,209; P < .001) and orthopedic operations (total knee replacement: $2,282 vs total hip replacement: $2,392; P < .001). The presence of a postoperative complication resulted in an increase in hospital payments by 25% and surgeon payments by 11%. CONCLUSIONS: Hospital and surgeon payments following routine general and orthopedic operations vary greatly. Patients with comorbid conditions and those who experienced a postoperative complication resulted in higher overall payments. Though significant variability existed at the surgeon level, hospital payments were responsible for the highest source of variability. PMID- 27554625 TI - Redox and Acid-Base Properties of Binuclear 4-Terphenyldithiophenolate Complexes of Nickel. AB - This work reports on the redox and acid-base properties of binuclear complexes of nickel from 1,4-terphenyldithiophenol ligands. The results provide insight into the cooperative electronic interaction between a dinickel core and its ligand. Donor/acceptor contributions flexibly adjust to stabilize different redox states at the metals, which is relevant for redox reactions like proton reduction. Proton transfer to the [S2 Ni2 ] core and Ni-H bond formation are kinetically favored over the thermodynamically favored yet unproductive proton transfer to ligand. PMID- 27554624 TI - Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation. AB - Glucocorticoid-induced osteoporosis (GIO) is one of the major side effects of long-term glucocorticoid (GC) therapy mediated mainly via the suppression of bone formation and osteoblast differentiation independently of GC receptor (GR) dimerization. Since microRNAs play a critical role in osteoblast differentiation processes, we investigated the role of Dicer dependent microRNAs in the GC induced suppression of osteoblast differentiation. MicroRNA sequencing of dexamethasone-treated wild-type and GR dimer-deficient mesenchymal stromal cells revealed GC-controlled miRNA expression in a GR dimer-dependent and GR dimer independent manner. To determine the functional relevance of mature miRNAs in GC induced osteoblast suppression, mice with an osteoblast-specific deletion of Dicer (Dicer(Runx2Cre)) were exposed to glucocorticoids. In vitro generated Dicer deficient osteoblasts were treated with dexamethasone and analyzed for proliferation, differentiation and mineralization capacity. In vivo, abrogation of Dicer-dependent miRNA biogenesis in osteoblasts led to growth retardation and impaired bone formation. However, subjecting these mice to GIO showed that bone formation was similar reduced in Dicer(Runx2Cre) mice and littermate control mice upon GC treatment. In line, differentiation of Dicer deficient osteoblasts was suppressed to the same extent as wild type cells by GC treatment. Therefore, Dicer-dependent small RNA biogenesis in osteoblasts plays only a minor role in the pathogenesis of GC-induced inhibition of bone formation. PMID- 27554626 TI - Mass in Solitary Intrathoracic Kidney Within Bochdalek Hernia. AB - Bochdalek hernia is a congenital defect in the diaphragm posterolaterally that allows abdominal contents to enter the thorax. Herniation and development of an intrathoracic kidney associated with this condition are uncommon, with an incidence less than 0.25%. Intrathoracic kidney is also the rarest form of renal ectopia, consisting of less than 5% of cases. We present a series of images from a case of a 55-year-old female with a right renal mass suspicious for malignancy in a solitary right intrathoracic kidney within Bochdalek hernia, who underwent an open right partial nephrectomy for definitive diagnosis and treatment. PMID- 27554627 TI - Re: Packiam et al: The Impact of Minimally Invasive Surgery on Major Iatrogenic Ureteral Injury and Subsequent Ureteral Repair During Hysterectomy: A National Analysis of Risk Factors and Outcome (Urology 2016;doi:10.1016/j.urology.2016.06.041). PMID- 27554628 TI - Inter-facility transfer of pediatric burn patients from U.S. Emergency Departments. AB - PURPOSE: To describe the epidemiology of pediatric burn patients seen in U.S. emergency departments (EDs) and to determine factors associated with inter facility transfer. METHODS: We analyzed data from the 2012 Nationwide Emergency Department Sample. Current American Burn Association (ABA) Guidelines were used to identify children <18 who met criteria for referral to burn centers. Burn patient admission volume was used as a proxy for burn expertise. Logistic models were fitted to examine the odds of transfer from low volume hospitals. RESULTS: In 2012, there were an estimated 126,742 (95% CI: 116,104-137,380) pediatric burn ED visits in the U.S. Of the 69,003 (54.4%) meeting referral criteria, 83.2% were in low volume hospitals. Only 8.2% of patients meeting criteria were transferred from low volume hospitals. Of the 52,604 (95% CI: 48,433-56,775) not transferred, 98.3% were treated and released and 1.7% were admitted without transfer; 54.7% of burns involved hands. CONCLUSIONS: Over 90% of pediatric burn ED patients meet ABA burn referral criteria but are not transferred from low volume hospitals. Perhaps a portion of the 92% of patients currently receiving definitive care in low volume hospitals are under-referred and would have improved clinical outcomes if transferred at the time of presentation. PMID- 27554629 TI - Steven Johnson Syndrome and Toxic Epidermal Necrolysis in a burn unit: A 15-year experience. AB - INTRODUCTION: The diffuse epidermal exfoliation seen in Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is similar to skin loss in second degree burns, and many of these patients are referred for treatment at burn centers. Treatment can differ markedly from center to center, and mortality can range from 25% to 70%, including a considerable morbidity. However, our experience over a 15-year period from 2000 to 2015 with 40 patients found a mortality rate of only 10% (4/40). The purpose of this paper is to discuss our treatment algorithm as a model for other centers treating SJS/TENs patients. METHODS: Records were reviewed for all patients admitted to the LAC+USC burn unit between 2000 and 2015 and 40 patients were identified with biopsy-proven SJS or TENS. These cases were reviewed for age, gender, initial and greatest TBSA, causative drug, pre-existing medical conditions, and morbidity and mortality. All data were entered into the SPSS statistical software package and all statistical analyses were performed using this program. RESULTS: Our treatment algorithm focused on early referral to a specialty burn unit, immediate discontinuation of the offending drug, fluid resuscitation, nutritional supplementation, and meticulous wound care. Average time to transfer to a burn unit was 3.36 days. Silver-releasing antimicrobial dressings were applied to the affected skin surface and changed every 3 days. Mupirocin coated petroleum gauze was used for facial involvement. Steroids were tapered and discontinued if initiated at an outside facility (58% of patients), and starting after 2001, all patients received a course of IVIG. All patients received fluid resuscitation and the majority received supplemental tube feedings (69%). Average length of total stay was 17.1 days and length of ICU stay 15.9 days. While 44% were transferred to another facility for further rehabilitative care, 37% of patients discharge to home. In patients discharged home with complete resolution of skin lesions, time to healing was an average of 14 days. DISCUSSION: With our 10% mortality rate in 40 patients, our study represents a relatively large study population while maintaining a relatively low mortality rate. The demographic data from our study largely aligns with the existing literature, and we therefore feel that our low mortality rate is due to our treatment algorithm, rather than to a less severe pathology in our patient population. This claim is supported by a standard mortality ratio of 1.68. This ratio proves a significantly improved mortality than would be expected based on disease severity on admission. PMID- 27554630 TI - Thigh burns from exploding E-cigarette. PMID- 27554631 TI - Utility and outcomes of hydroxocobalamin use in smoke inhalation patients. AB - INTRODUCTION: Hydroxocobalamin has been available for use for suspected cyanide toxicity in smoke inhalation patients in the United States since 2006. Our study compares outcomes of patients who received hydroxocobalamin to historical controls who did not. METHODS: In this retrospective review, patients administered hydroxocobalamin (2008-2014) were compared to historical controls (2002-2008). Patients <18 years, patients who received an alternate antidote, and patients without suspicion of smoke inhalation injury were excluded. Mortality was the primary outcome. Secondary outcomes evaluated were 7-day change in creatinine, culture-proven pneumonia, days on mechanical ventilation, ventilator- free days (VFD), ICU length of stay (ICU LOS), and hospital length of stay (HLOS). RESULTS: A total of 138 patients in the hydroxocobalamin group and 135 in the control group were identified. Mortality rate was similar between both groups (29% vs. 28%, p=0.90). Hydroxocobalamin was associated with lower pneumonia rate (23% vs. 49%, p<0.01), less ventilator days (4 days vs. 7 days, p<0.01), and increased VFD (20 days vs. 11 days, p=0.01) compared to controls. Shorter ICU LOS (6 days vs. 10 days, p=0.03) and a trend toward lower HLOS (7 day vs. 11 days, p=0.06) were also found in patients who received hydroxocobalamin. CONCLUSIONS: Routine administration was associated with lower rate of pneumonia, faster liberation from the ventilator, and reductions in intensive care unit stay. Burn centers should consider its empiric use in suspected smoke inhalation patients. PMID- 27554632 TI - Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy. AB - OBJECTIVE: Mutations in ion channels genes are potential cause of cardiomyopathy. The SCN5A gene (sodium channel, voltage gated, type V alpha subunit gene; 3p21) belongs to the family of cardiac sodium channel genes. Mutations in SCN5A gene lead to decreased Na+ current and ion unbalance. The SCN5A gene mutations are found in approximately 2% of patients with dilated cardiomyopathy (DCM), and they may be potential phenotype modifiers in hypertrophic cardiomyopathy (HCM). The role of SCN5A gene mutations in cardiomyopathy is not fully elucidated. METHODS: Three selected exons (12, 20, and 21) of the SCN5A gene in the cohort of 58 East Slovak patients with dilated and HCM were analyzed by the Sanger sequencing method in order to detect etiopathogenic mutations associated with dilated and HCM. RESULTS: The mutation screening of three selected exons of SCN5A gene in the cohort of 27 DCM, 12 HCM patients, and 16 controls identified 10 missense genetic variants. Three of them (T1247I, A1260D, and G1262S), all in exon 21 of the SCN5A gene, were potentially damaging and disease-causing variants. CONCLUSION: Data from this study demonstrate that SCN5A gene variants have important role in the etiopathogenesis of dilated and HCM. PMID- 27554633 TI - A Simple Paper-Based Colorimetric Device for Rapid Mercury(II) Assay. AB - Contamination of the environment by mercury(II) ions (Hg(2+)) poses a serious threat to human health and ecosystems. Up to now, many reported Hg(2+) sensors require complex procedures, long measurement times and sophisticated instrumentation. We have developed a simple, rapid, low cost and naked-eye quantitative method for Hg(2+) environmental analysis using a paper-based colorimetric device (PCD). The sample solution to which platinum nanoparticles (PtNPs) have been added is dispensed to the detection zone on the PCD, where the 3,3,5,5-tetramethylbenzidine (TMB) substrate has been pre-loaded. The PtNPs effect a rapid oxidization of TMB, inducing blue colorization on the PCD. However, Hg(2+) in the solution rapidly interact with the PtNPs, suppressing the oxidation capacity and hence causing a decrease in blue intensity, which can be observed directly by the naked eye. Moreover, Hg(2+) at concentrations as low as 0.01 uM, can be successfully monitored using a fiber optic device, which gives a digital readout proportional to the intensity of the blue color change. This paper-based colorimetric device (PCD) shows great potential for field measurement of Hg(2+). PMID- 27554634 TI - PZP and PAI-2: Structurally-diverse, functionally similar pregnancy proteins? AB - Pregnancy zone protein (PZP) and plasminogen activator inhibitor type 2 (PAI-2) are two multifunctional proteins that are elevated in normal pregnancy and numerous other inflammatory states. Both proteins were originally identified as protease inhibitors, but current evidence supports the notion that they may also function as modulators of T-helper cells and/or extracellular chaperones. Exacerbated inflammation, fibrinolytic disturbances and misfolded proteins are all implicated in the pathology of preeclampsia, a leading cause of maternal and foetal mortality and morbidity. Notably, reduced levels of PZP or PAI-2 are associated with preeclampsia and clarification of their diverse functions in normal pregnancy could provide much needed insight regarding the pathogenesis of this disorder. Given that inflammation and protein misfolding underlie the pathology of a very large number of disorders, the contributions of PZP and PAI-2 to extracellular proteostasis and immunoregulation could be broad-reaching. PMID- 27554635 TI - Evidence for an expanded time-window to mitigate a reactivated fear memory by tamoxifen. AB - The mechanisms underpinning the persistence of emotional memories are inaccurately understood. Advancing the current level of understanding with regards to this aspect is of potential translational value for the treatment of post-traumatic stress disorder (PTSD), which stems from an abnormal aversive memory formation. Tamoxifen (TMX) is a drug used in chemotherapy for breast cancer and associated with poor cognitive performances. The present study investigated whether the systemic administration of TMX (1.0-50mg/kg) during and/or beyond the reconsolidation time-window could attenuate a reactivated contextual fear memory in laboratory animals. When administered 0, 6 or 9h (but not 12h) post-memory retrieval and reactivation, TMX (50mg/kg) reduced the freezing behavior in male rats re-exposed to the paired context on day 7, but not on day 1, suggesting a specific impairing effect on memory persistence. Importantly, this effect lasts up to 21 days, but it is prevented by omitting the memory retrieval or memory reactivation. When female rats in the diestrous or proestrous phase were used, the administration of TMX 6h after retrieving and reactivating the fear memory also impaired its persistence. Altogether, regardless of the gender, the present results indicate that the TMX is able to disrupt the persistence of reactivated fear memories in an expanded time-window, which could shed light on a new promising therapeutic strategy for PTSD. PMID- 27554636 TI - Pharmacodynamic effects of suvorexant and zolpidem on EEG during sleep in healthy subjects. AB - The objective of this study was to evaluate sleep electrophysiology in healthy subjects after bedtime administration of therapeutic doses of two insomnia treatments - the orexin receptor antagonist suvorexant or the GABAergic agonist zolpidem. Eighteen healthy men received single bedtime doses of suvorexant 20mg, zolpidem 10mg, or placebo in a double-blinded, randomized, balanced 3-period crossover study. EEG power spectral densities during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were recorded in a polysomnography (PSG) laboratory using a 19-lead EEG recording array. Spectral density was analyzed for each lead for frequencies between 1-32Hz. During NREM and REM sleep, zolpidem treatment reduced spectral density across theta and alpha frequency bands in all leads. In contrast, suvorexant had no significant effects on spectral density in any frequency band during NREM sleep, and modestly increased spectral density in the theta frequency band during REM sleep. Although the study was not designed to detect effects on PSG sleep endpoints in healthy subjects, both suvorexant and zolpidem increased mean total sleep time and sleep efficiency. Zolpidem reduced latency to persistent sleep whereas suvorexant did not. Suvorexant decreased wake after sleep onset, whereas zolpidem did not. These findings suggest that EEG power spectral density profile after administration of suvorexant in healthy subjects more closely approximates placebo sleep physiology than after zolpidem treatment. PMID- 27554637 TI - No meaningful association between suicidal behavior and the use of IL-17A neutralizing or IL-17RA-blocking agents. AB - INTRODUCTION: An emerging class of agents blocking IL-17 signaling represents a very promising therapeutic approach. One of these agents, brodalumab, has been associated with an increased risk of suicide behavior. Areas covered: This review sought to provide an overview strictly focused on suicide behavior signals related to the use of IL-17 agents. Data collection regarding this peculiar safety aspect was primarily based on: (i) a revision of safety outcomes belonging to phase II and phase III trials; (ii) a systematic search using the Pubmed Medline database; and (iii) collecting recent data issued as posters or communications in eminent international meetings. Expert opinion: Whilst secukinumab and ixekizumab were not associated with increased signal of suicidal behavior, being recently approved for the treatment of psoriasis by EMA and FDA, brodalumab raised concern because of suicide behavior cases that led to pause momentarily its development program during pre-marketing stage before obtaining the positive recommendation by an FDA advisory panel for its approval. Indeed, a careful re-evaluation of brodalumab safety profile is being performed and no evidence clarified a significant association or a pathogenic mechanism linking brodalumab treatment to the risk of suicidal behavior, suggesting that cases of suicidal behavior accidentally occurred during brodalumab trials. PMID- 27554638 TI - Distal mean nocturnal baseline impedance on pH-impedance monitoring predicts reflux burden and symptomatic outcome in gastro-oesophageal reflux disease. AB - BACKGROUND: Mean nocturnal baseline impedance (MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden. AIM: To assess the predictive value of MNBI on symptomatic outcomes after anti-reflux therapy. METHODS: In this prospective observational cohort study, pH-impedance studies performed over a 5 year period were reviewed. Baseline impedance was extracted from six channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal oesophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7 and 9 cm, and 15 and 17 cm respectively. Symptomatic outcomes were measured as changes in global symptom severity (GSS, rated on 100-mm visual analogue scales) on prospective follow-up after medical or surgical anti-reflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes. RESULTS: Of 266 patients, 135 (50.8%) were tested off proton pump inhibitor (PPI) therapy and formed the study cohort (52.1 +/- 1.1 years, 63.7% F). The 59 with elevated acid exposure time (AET) had lower composite and distal MNBI values than those with physiological AET (P < 0.0001), but similar proximal MNBI (P = 0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r = -0.5, P < 0.001), but not proximal MNBI (Pearson's r = 0, P = 0.72). After prospective follow-up (94 patients were followed up for 3.1 +/- 0.2 years), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement. CONCLUSIONS: Distal oesophageal MNBI negatively correlates with AET and, when assessed off PPI therapy, is independently predictive of symptomatic improvement following anti reflux therapy. PMID- 27554639 TI - TAZ regulates cell proliferation and sensitivity to vitamin D3 in intrahepatic cholangiocarcinoma. AB - The transcriptional coactivator with PDZ binding motif (TAZ) is reported as one of the nuclear effectors of Hippo-related pathways. TAZ is found overexpressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in Intrahepatic Cholangiocarcinoma (ICC). In this study, we found that TAZ is expressed more in ICC tissues than in peritumoral tissue, and a robust expression of TAZ is correlated with a lower overall survival rate of ICC patients after hepatectomy. TAZ knockdown results in an increase in cell apoptosis, a promotion of cell-cycle arrest and a decrease in tumor size and weight in vivo through an increased expression of p53. Vitamin D3 can also inhibit cell proliferation by promoting p53 expression in ICC cells. A reduction in TAZ can also enhance the sensitivity of tumor cells to vitamin D by regulating the p53/CYP24A1 pathway. In conclusion, TAZ is associated with the proliferation and drug-resistance of ICC cells, and could be a novel therapeutic target for the treatment of ICC. PMID- 27554640 TI - Parent Perceptions of Sexual Education Needs for Their Children With Autism. AB - : Primary responsibility for sexual education for adolescents with autism spectrum disorder falls on parents who have reported a lack of professional and material support. The purpose of this study was to 1) describe parent perceptions of sexual education needs of their children aged 14-20 with an autism spectrum disorder diagnosis and 2) determine parent-preferred mechanisms of delivery for tailored educational intervention strategies. DESIGN AND METHODS: The study aims were accomplished by a qualitative research design using focus groups and telephone interviews assisted by a structured interview guide. Study methods and analysis were guided by social marketing principles. RESULTS: A total of 15 parents (5 participated in 1 focus group and 10 completed individual interviews) acknowledged their primary role in providing sexual education for their children and confirmed a need for resources to assist them in this role. All parents in this study found that some level of sexual education was necessary and important and that all children had been introduced to sexual information but in varying degrees. Topic preferences included those that would increase the recognition of healthy relationships, provide a measure of self-protection, and ameliorate undesirable consequences of sexual activity. Parents were knowledgeable about how their children best learned and suggested future interventions use technology interfaces with engaging displays and allow for individualized content. CONCLUSION AND IMPLICATIONS: These findings highlight a need for additional research and enhanced clinical services to ensure that adolescents with autism spectrum disorder have their informational needs met, are able to avoid risks, and have the greatest capacity for a healthy sexuality as they transition to adulthood. PMID- 27554641 TI - Chronic pancreatitis: Do serum biomarkers provide an association with an inflammageing phenotype? AB - BACKGROUND: Chronic pancreatitis is an inflammatory disorder of the pancreas that is associated with accelerated mortality for patients suffering from this disease. The association between chronic inflammation and accelerated biological ageing has been well described and is often referred to as "inflammageing". In this review we seek to determine how systemic inflammation in chronic pancreatitis may contribute to an accelerated ageing phenotype. METHODS: A systematic literature search with a predefined search protocol was performed on Medline, Embase and Cochrane libraries according to the PRISMA guidelines. RESULTS: The initial search identified 499 studies. After title, abstract and full text screen of the search results, 20 were included for further evaluation. In the 20 remaining articles 41 inflammatory mediators were identified - mainly involved in chronic inflammation, fibrosis and particularly cardinal features of inflammageing such as sarcopenia and osteoporosis. CONCLUSION: Chronic pancreatitis is associated with elevated levels of inflammatory mediators many of which are associated with an accelerated ageing phenotype and may explain some of the clinical sequelae of this disease. PMID- 27554642 TI - High-Velocity Microsprays Enhance Antimicrobial Activity in Streptococcus mutans Biofilms. AB - Streptococcus mutans in dental plaque biofilms play a role in caries development. The biofilm's complex structure enhances the resistance to antimicrobial agents by limiting the transport of active agents inside the biofilm. The authors assessed the ability of high-velocity water microsprays to enhance delivery of antimicrobials into 3-d-old S. mutans biofilms. Biofilms were exposed to a 90 degrees or 30 degrees impact, first using a 1-um tracer bead solution (109 beads/mL) and, second, a 0.2% chlorhexidine (CHX) or 0.085% cetylpyridinium chloride (CPC) solution. For comparison, a 30-s diffusive transport and simulated mouthwash were also performed. Confocal microscopy was used to determine number and relative bead penetration depth into the biofilm. Assessment of antimicrobial penetration was determined by calculating the killing depth detected by live/dead viability staining. The authors first demonstrated that the microspray was able to deliver significantly more microbeads deeper in the biofilm compared with diffusion and mouthwashing exposures. Next, these experiments revealed that the microspray yielded better antimicrobial penetration evidenced by deeper killing inside the biofilm and a wider killing zone around the zone of clearance than diffusion alone. Interestingly the 30 degrees impact in the distal position delivered approximately 16 times more microbeads and yielded approximately 20% more bacteria killing (for both CHX and CPC) than the 90 degrees impact. These data suggest that high-velocity water microsprays can be used as an effective mechanism to deliver microparticles and antimicrobials inside S. mutans biofilms. High shear stresses generated at the biofilm-burst interface might have enhanced bead and antimicrobial delivery inside the remaining biofilm by combining forced advection into the biofilm matrix and physical restructuring of the biofilm itself. Further, the impact angle has potential to be optimized both for biofilm removal and active agents' delivery inside biofilm in those protected areas where some biofilm might remain. PMID- 27554643 TI - Children and young people's views on access to a web-based application to support personal management of long-term conditions: a qualitative study. AB - BACKGROUND: An exploration of children and young people's views on a proposed web based application to support personal management of chronic kidney disease at home is important for developing resources that meet their needs and preferences. METHODS: As part of a wider study to develop and evaluate a web-based information and support application for parents managing their child's chronic kidney disease, qualitative interviews were conducted with 26 children and young people aged 5-17 years. Interviews explored their views on content of a proposed child and young person-appropriate application to support personal management of their condition. Data were analysed by using framework technique and self-efficacy theory. RESULTS: One overarching theme of Access and three subthemes (information, accessibility and normalization) were identified. Information needed to be clear and accurate, age appropriate and secure. Access to Wi-Fi was essential to utilize information and retain contact with peers. For some, it was important to feel 'normal' and so they would choose not to access any care information when outside of the hospital as this reduced their ability to feel normal. CONCLUSION: Developing a web-based application that meets children and young peoples' information and support needs will maximize its utility and enhance the effectiveness of home-based clinical caregiving, therefore contributing to improved outcomes for patients. PMID- 27554644 TI - Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report. AB - BACKGROUND Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. CASE REPORT The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated. CONCLUSIONS Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant interactions with the patient's immunosuppressive regimens. Still, the peritransplant setting is a very demanding environment for anti-HCV therapy, and further studies are needed. PMID- 27554645 TI - [Should treatment of chronic obstructive pulmonary disease be based on multidimensional scales?] PMID- 27554646 TI - RhoE Is a Pro-Survival p53 Target Gene that Inhibits ROCK I-Mediated Apoptosis in Response to Genotoxic Stress. PMID- 27554647 TI - Mangrove forests. AB - Mangrove forests are unique ecosystems that are important for human populations. PMID- 27554648 TI - Prosociality. AB - Prosociality refers to behaviours that are intended to benefit others. This definition appears to be so straightforward that it hardly bears mentioning: like certain forms of adult entertainment, we know it when we see it. Yet, determining what counts as prosocial is not as simple as it first appears. There are numerous behaviours that appear prosocial but, on scrutiny, may not have been intended and motivated for the well-being of others. Consider a banal scenario: a seated passenger on a crowded bus stands up and someone takes his seat. Did the person standing up intend that someone else take the seat? Perhaps he was getting off the bus at the next stop and did not care if anyone sat there. But what if he remained standing for several stops, or made an overt gesture such as waving his hand toward the seat? In that case it is more likely that he intended for someone to have his place on the bus. But what about his underlying motives? Maybe he was putting himself in a better position to pick the pocket of the person sitting down. Less sinister possibilities include trying to impress the person who took his seat - trying to improve his reputation, his social standing, as it were. Or maybe, just maybe, he intended for another passenger to sit comfortably, to increase the happiness of a stranger, with no ulterior motives. PMID- 27554649 TI - Polarization vision seldom increases the sighting distance of silvery fish. AB - Although the function of polarization vision, the ability to discern the polarization characteristics of light, is well established in many terrestrial and benthic species, its purpose in pelagic species (squid and certain fish and crustaceans) is poorly understood [1]. A long-held hypothesis is that polarization vision in open water is used to break the mirror camouflage of silvery fish, as biological mirrors can change the polarization of reflected light [2,3]. Although, the addition of polarization information may increase the conspicuousness of silvery fish at close range, direct evidence that silvery fish - or indeed any pelagic animal - are visible at longer distances using polarization vision rather than using radiance (i.e. brightness) vision is lacking. Here we show, using in situ polarization imagery and a new visual detection model, that polarization vision does not in fact appear to allow viewers to see silvery fish at greater distances. PMID- 27554650 TI - Evidence for meiotic sex in bdelloid rotifers. AB - In their study of genetic exchange in the bdelloid rotifer Adineta vaga, Debortoli et al. [1] conclude that the patchwork pattern of allele sharing among three individuals in the genomic regions they examined is "...unlikely to arise in cases of PTH (Oenothera-like) meiosis since haplotypes are transferred as entire blocks..." and therefore that "Genetic exchange among bdelloid rotifers is more likely due to horizontal gene transfer than to meiotic sex." This assumes without justification that horizontal gene transfer (HGT) in bdelloids precludes the sexual transmission of entire haplotypes, for which we have reported evidence in the bdelloid Macrotrachela quadricornifera[2]. And it does not consider the contribution to such a patchwork pattern that would result from conversion and subsequent outcrossing, even in Oenothera-like systems. PMID- 27554651 TI - Response to Signorovitch et al. AB - Signorovitch et al.[1] comment that an Oenothera-like meiosis [2] could produce a pattern similar to what we observed in our study of natural isolates of the bdelloid rotifer Adineta vaga, which we attributed to horizontal gene transfers (HGTs) [3]. Indeed, our HGT hypothesis appears at first sight difficult to conciliate with their observation of a congruent pattern of allele sharing at four large loci possibly located on different chromosomes [4]. However, one might imagine conditions under which massive horizontal gene transfer between bdelloid individuals could produce such a pattern, notably if the individuals involved had previously lost most of their heterozygosity because of their exposure to frequent desiccation (which produces DNA double-strand breaks [5]). In the published A. vaga genome the loss of heterozygosity due to large-scale gene conversion events or break-induced replication covers only about 10% of the genome [6], but this percentage may be much higher in environmental isolates that often experience dessication. Besides, if an Oenothera-like mode of meiosis occurs in bdelloids frequently enough to be detected in a single sampling of 29 individuals (as in [4]), one would expect males and meiosis to be observed at least occasionally, and instances of congruent allele sharing across loci should turn up frequently in genetic surveys. This was not the case in [3]: among the 82 A. vaga individuals sequenced for four nuclear markers, no trio of individuals presented congruent patterns of shared sequences at different loci. For these reasons, and in the absence of any direct evidence for an Oenothera-like meiosis in bdelloids, we still consider inter-bdelloid HGTs a more parsimonious explanation for our results. PMID- 27554652 TI - Social Evolution: The Force of the Market. AB - Biological market forces shape patterns of cooperation typical of small-scale human societies that are organized by division of labor based on age and gender. Labor specialization promotes trade, while supply and demand affect the amount individuals exchange for commodities. PMID- 27554653 TI - Evolution: Fossil Ears and Underwater Sonar. AB - A key innovation in the history of whales was the evolution of a sonar system together with high-frequency hearing. Fossils of an archaic toothed whale's inner ear bones provide clues for a stepwise emergence of underwater echolocation ability. PMID- 27554654 TI - Behavior: Warriors Shaking Hands. AB - A basic precondition of social life is that conflicts must be resolved when you need each other. A new study shows that men affiliate more after one-on-one conflicts than women. This reflects the deep evolutionary history of male bonding. PMID- 27554655 TI - Vector Biology: Tyrosine Degradation Protects Blood Feeders from Death via La Grande Bouffe. AB - Blood-feeding arthropods digest vast amounts of host-blood nutrients. A new study suggests that tyrosine degradation is essential for the survival of blood-fed kissing bugs, mosquitoes, and ticks. This finding presents a promising target for the control of these disease vectors. PMID- 27554656 TI - Sleep: Switching Off the Off-Switch. AB - What are the synaptic drives controlling the sleep-wake circuitry in the mammalian brain? In a new study it was found that GABAergic cells in posterior lateral hypothalamus inhibit sleep-promoting anterior hypothalamic cells to cause waking, whereas their inhibition augments sleep. PMID- 27554657 TI - Growth: A Model for Establishing Cell Size and Shape. AB - New experiments reveal that the relative growth between cell surface area and volume are key determinants of the shape and size of rod-like bacteria. These results are synthesized into a relative-growth model that applies to questions ranging from morphogenesis to cell-cycle timing. PMID- 27554658 TI - Ecology: The Tropical Deforestation Debt. AB - Tropical deforestation is a significant cause of global carbon emissions and biodiversity loss. A new study shows that deforestation today leaves a carbon and biodiversity debt to be paid over subsequent years. This has potentially profound implications for forest conservation. PMID- 27554659 TI - Microglia: Senescence Impairs Clearance of Myelin Debris. AB - Growing evidence highlights the crucial physiological functions of microglia that rely on their phagocytic activities, which can be compromised with age. A new study reports the impaired clearance of myelin debris by microglia in the brain, leading to insoluble lysosomal inclusions and contributing to the immune dysfunction and senescence of these cells. PMID- 27554660 TI - Fungal Evolution: Mucor and Phycomyces See Double. AB - Newly available genome sequences of two Mucoralean fungi, Phycomyces blakesleeanus and Mucor circinelloides, provide evidence for an ancient whole genome duplication that contributed to the generation of expanded gene families. These fungi have robust responses to light that can be correlated with the expansion of gene networks involved in light sensing and signaling. PMID- 27554661 TI - Hybrid-fusion SPECT/CT systems in parathyroid adenoma: Technological improvements and added clinical diagnostic value. AB - Nuclear medicine traditionally employs planar and single photon emission computed tomography (SPECT) imaging techniques to depict the biodistribution of radiotracers for the diagnostic investigation of a range of disorders of endocrine gland function. The usefulness of combining functional information with anatomy derived from computed tomography (CT), magnetic resonance imaging (MRI), and high resolution ultrasound (US), has long been appreciated, either using visual side-by-side correlation, or software-based co-registration. The emergence of hybrid SPECT/CT camera technology now allows the simultaneous acquisition of combined multi-modality imaging, with seamless fusion of 3D volume datasets. Thus, it is not surprising that there is growing literature describing the many advantages that contemporary SPECT/CT technology brings to radionuclide investigation of endocrine disorders, showing potential advantages for the pre operative locating of the parathyroid adenoma using a minimally invasive surgical approach, especially in the presence of ectopic glands and in multiglandular disease. In conclusion, hybrid SPECT/CT imaging has become an essential tool to ensure the most accurate diagnostic in the management of patients with hyperparathyroidism. PMID- 27554662 TI - Investigation of sinonasal anatomy via low-dose multidetector CT examination in chronic rhinosinusitis patients with higher risk for perioperative complications. AB - The aim of the study was to compare visualisation of the surgically relevant anatomical structures via low- and standard-dose multidetector CT protocol in patients with chronic rhinosinusitis (CRS) and higher risk for perioperative complications (i.e. presence of bronchial asthma, history of sinus surgery and advanced nasal polyposis). 135 adult CRS patients were divided randomly into standard-dose (120 kVp, 100 mAs) or low-dose CT groups (120 kVp, 45 mAs). The detectability of the vital anatomical structures (anterior ethmoid artery, optic nerve, cribriform plate and lamina papyracea) was scored using a five-point scale (from excellent to unacceptable) by a radiologist and sinus surgeon. Polyp sizes were quantified endoscopically according to the Lildholdt's scale (LS). Olfactory function was tested with the "Sniffin' Sticks" test. On the low-dose CT images, detectability ranged from 2.42 (better than poor) for cribriform plate among anosmic cases to 4.11 (better than good) for lamina papyracea in cases without nasal polyps. Identification of lamina papyracea on low-dose scans was significantly worse in each group and the same was the case with cribriform plates in patients with advanced polyposis and anosmia. Cribriform plates were the most poorly identified (between poor and average) among all the structures on low-dose images. Identification of anterior ethmoid artery (AEA) with reduced dose was insignificantly worse than with standard-dose examination. The AEA was scored as an average-defined structure and was the second weakest visualised. In conclusion, preoperatively, low-dose protocols may not sufficiently visualise the surgically relevant anatomical structures in patients with CRS and bronchial asthma, advanced nasal polyps (LS > 2) and history of sinus surgery. Low mAs value enables comparable detectability of sinonasal landmarks with standard-dose protocols in patients without analysed risk factors. In the context of planned surgery, the current preferences of the tube should be carefully evaluated for different patient constitutions to minimise the risk of complications. PMID- 27554663 TI - Quality of life before and after sinonasal surgery: a population-based matched cohort study. AB - A population-based matched cohort study was conducted to explore how the quality of life (QoL) changes in patients with septal deviation or recurrent/chronic rhinosinusitis after septoplasty (SP) and endoscopic sinus surgery (ESS). We also compared the QoL of the surgical cohort with that of a concurrently collected healthy cohort. We collected data on QoL in a population-based surgical cohort of 160 patients residing in one health care district (population 405,000) in Northern Finland, and in a control cohort comprised of 206 age- and sex-matched randomly selected subjects residing in Finland (population 5,470,000). QoL was assessed at entry and 12 months later with the Sino-Nasal Outcome Test-22 (SNOT 22) and the RAND-36 generic instruments. Seventy-six SP and 84 ESS patients and 206 controls were enrolled. At entry, the mean SNOT-22 scores of the SP and ESS groups were similar (34.9 and 35.1, respectively) and both were significantly worse than the control group (17.7). At 12 months, the mean SNOT-22 score had improved after SP [change 15.7, 95 % confidence interval (CI) 11.4-19.9] and ESS (change 18.0, 95 % CI 12.4-20.9) and almost reached that of the control group, which remained unchanged. The benefit was similar regardless of the surgical indication. At 12 months, mean RAND-36 scores had improved in most domains in both patient groups and remained unchanged in the controls. After appropriate surgical criteria, both SP and ESS are effective in enhancing QoL on the population level, and postoperative QoL almost reaches the level of the control population. PMID- 27554664 TI - Variation in treatment and outcome in the early stage oral cavity squamous cell carcinoma. AB - This study aims to determine the survival impact of patient characteristics and treatment options associated with the early stage oral cavity squamous cell carcinoma, OCSCC. The methods are analysis of Irish cancer database examining T1/2, N0, and M0 cases of OCSCC from 1997 to 2007 inclusive. In total, 397 cases were identified. Anterolateral tongue accounted for 52.9 % of cases. Increased age at diagnosis and smoking are independent prognostic survival indicators associated with poorer outcomes. Surgery as the initial intervention was associated with significantly better survival outcomes, while surgery and adjuvant radiotherapy significantly worse outcomes. Surgical intervention is recommended as the first-line treatment in the early stage OCSCC in combination with elective neck dissection. PMID- 27554665 TI - Audiometric evaluation in patients with Alzheimer's disease. AB - The objective of this study is to assess the validity of ASSR as a complementary diagnostic test for peripheral hearing loss by proving a significant correlation between behavioral thresholds and ASSR. The design used in this study is monocentric prospective study from November 2014 to April 2015. The setting used in this study is the ENT-Head and Neck Surgery Department and Geriatrics Department in a French Regional and University Hospital. The participants are patients over 75 years with cognitive impairment (Alzheimer's disease or mild cognitive impairment) with a Mini-Mental State Examination score under 27/30 and without hearing aids. Exclusion criteria were: otoscopic and middle ear abnormalities, retro-cochlear lesion, other types of dementia, and central nervous system disease altering cerebral lateralization. The intervention used in this study is pure-tone audiometry, speech audiometry, dichotic listening test, and auditory steady-state responses recording. The correlations between these exams were studied with Pearson's correlation coefficient and Student's t test. Results were significant if p < 0.05. Twenty-three ears were analyzed from 12 patients. There were six women and six men with cognitive impairment, mean age 82.1 (+/-4.6) years, and mean MMSE score that was 21.3/30 (+/-5.7). The correlation between pure-tone audiometry and ASSR was significant for all frequencies: r = 0.55 (p = 0.006) for 500 Hz, r = 0.58 (p = 0.005) for 1000 Hz, r = 0.61 (p = 0.003) for 2000 Hz, and r = 0.66 (p = 0.002) for 4000 Hz. There was no significant correlation between the MMSE and the difference between ASSR and PTA on each frequency. The dichotic listening test showed a right ear advantage (50.9 %, p = 0.039). The ASSR in patients with cognitive impairment and understanding troubles is a promising complementary technique to estimate the hearing thresholds. PMID- 27554666 TI - The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies, aqueous pK a, and cyclohexane-water log D. AB - We predict cyclohexane-water distribution coefficients (log D 7.4) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the "embedded cluster reference interaction site model" (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (pK a) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the "Minnesota Solvation Database" (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol-1 for water and 0.8-0.9 kcal mol-1 for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical pK a model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2-3 for each solvent and two for the pK a) for training solvation and acidity models. Applying the final models to the log D 7.4 dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0-2.1 for the RMSE with the first and 2.2-2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed. PMID- 27554667 TI - Computed tomography for the detection of distal radioulnar joint instability: normal variation and reliability of four CT scoring systems in 46 patients. AB - OBJECTIVES: The diagnosis of distal radioulnar joint (DRUJ) instability is clinically challenging. Computed tomography (CT) may aid in the diagnosis, but the reliability and normal variation for DRUJ translation on CT have not been established in detail. The aim of this study was to evaluate inter- and intraobserver agreement and normal ranges of CT scoring methods for determination of DRUJ translation in both posttraumatic and uninjured wrists. MATERIALS AND METHODS: Patients with a conservatively treated, unilateral distal radius fracture were included. CT scans of both wrists were evaluated independently, by two readers using the radioulnar line method, subluxation ratio method, epicenter method and radioulnar ratio method. The inter- and intraobserver agreement was assessed and normal values were determined based on the uninjured wrists. RESULTS: Ninety-two wrist CTs (mean age: 56.5 years, SD: 17.0, mean follow-up 4.2 years, SD: 0.5) were evaluated. Interobserver agreement was best for the epicenter method [ICC = 0.73, 95 % confidence interval (CI) 0.65-0.79]. Intraobserver agreement was almost perfect for the radioulnar line method (ICC = 0.82, 95 % CI 0.77-0.87). Each method showed a wide normal range for normal DRUJ translation. Normal range for the epicenter method is -0.35 to -0.06 in pronation and -0.11 to 0.19 in supination. CONCLUSION: DRUJ translation on CT in pro- and supination can be reliably evaluated in both normal and posttraumatic wrists, however with large normal variation. The epicenter method seems the most reliable. Scanning of both wrists might be helpful to prevent the radiological overdiagnosis of instability. PMID- 27554668 TI - Empirically Derived Dietary Patterns and Hypertension Likelihood: A Meta Analysis. AB - BACKGROUND/AIMS: Dietary patterns, which represent whole-diet and a complex integration of food and nutrient, have been reported to play an important role in the development of hypertension. However, the results have yielded conflicting findings. Herein, we performed this meta-analysis to evaluate the associations between different dietary patterns and the likelihood of hypertension. METHODS: MEDLINE and EBSCO were searched to identify relevant articles published until the end of March 2016. A random-effects model was used to account for possible heterogeneity between studies.A total of twenty-seven studies met the inclusion criteria and were included in this meta-analysis. RESULTS: There was evidence of a decreased likelihood for hypertension in the highest compared with the lowest categories of healthy pattern (odds ratio (OR)=0.81; 95% confidence interval(CI): 0.67-0.97; P=0.02). An increased likelihood of hypertension was shown for the highest compared with the lowest category of heavy drinking pattern (OR=1.62; 95% CI: 1.16-2.26; P=0.004), whereas no statistically significant association with western-style and light-moderate drinking pattern were observed(OR=1.04, 95% CI: 0.83-1.31; OR=1.20, 95% CI:0.94- 1.53; P>0.05). CONCLUSIONS: Our results of this systematic review and meta-analysis suggest that dietary pattern may be associated with the likelihood of hypertension. PMID- 27554670 TI - Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients. AB - OBJECTIVE: The current study was carried out to assess the effects of omega-3 fatty acid and alpha-tocopherol co-supplementation on malnutrition-inflammation score (MIS), biomarkers of inflammation and oxidative stress in chronic hemodialysis (HD) patients. METHODS: In a randomized double-blind placebo controlled clinical trial, 120 patients with chronic HD were included. Patients were randomly allocated into four groups to receive: (1) 1250 mg/day omega-3 fatty acid containing 600 mg EPA and 300 mg DHA + alpha-tocopherol placebo (n = 30); (2) 400 IU/day alpha-tocopherol + omega-3 fatty acids placebo (n = 30); (3) 1250 mg omega-3 fatty acids/day + 400 IU/day alpha-tocopherol (n = 30); and (4) omega-3 fatty acids placebo + alpha-tocopherol placebo (n = 30) for 12 weeks. RESULTS: After 12 weeks of intervention, all three groups of alpha-tocopherol only, individual omega-3 fatty acids, and combined omega-3 fatty acids and alpha tocopherol experienced a significant improvements in MIS compared with the placebo group; however, improvements were much greater in the individual omega-3 fats (-1.4 +/- 1.4) and combined omega-3 fats and alpha-tocopherol (-1.1 +/- 2.3) groups compared with alpha-tocopherol group alone (-0.5 +/- 1.7, P = 0.004). Furthermore, both individual and combined intervention with omega-3 fats and alpha-tocopherol led to a significant increase in plasma nitric oxide (NO) (combined group: +17.6 +/- 29.3; alpha-tocopherol: +43.1 +/- 36.3; omega-3 fats: +31.0 +/- 40.0; and placebo: -0.5 +/- 18.5 umol/L, respectively, P < 0.001) and total antioxidant capacity (TAC) (+64.9 +/- 113.6, +53.0 +/- 144.6, +57.6 +/- 157.8 and -69.9 +/- 215.1 mmol/L, respectively, P = 0.004) levels. CONCLUSION: Overall, omega-3 fatty acids and alpha-tocopherol co-supplementation for 12 weeks among HD patients improved MIS, plasma NO and TAC levels. Future studies with longer duration of the intervention are needed to confirm the validity of our findings. CLINICAL REGISTRATION: www.irct.ir as IRCT201410245623N28. PMID- 27554669 TI - The critical roles of mitophagy in cerebral ischemia. AB - Mitochondria play a key role in various cell processes including ATP production, Ca2+ homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia. PMID- 27554671 TI - Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma. AB - PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown. METHODS: A total of 180 patients who underwent radical nephroureterectomy (RNU) for UTUC were included in this retrospective analysis. The associations of pretreatment serum PChE levels with clinicopathological characteristics and clinical outcomes were assessed. RESULTS: The median (IQR) pretreatment serum PChE level was 6385 (5449-7260) IU/L, and an optimal cutoff value of 5336 IU/L was set according to ROC analysis. Decreased pretreatment serum PChE levels were significantly correlated with older patient age, higher preoperative chronic kidney disease (CKD) stage and pT stage (all P < 0.05). On multivariate analysis, adjusting for preoperative variables, decreased pretreatment serum PChE levels independently predicted higher pT stage (P = 0.011). Moreover, Kaplan-Meier curves suggested that patients with PChE levels <5336 IU/L were predicted to have a shorter overall survival (OS) and cancer specific survival (CSS) than those with PChE levels >=5336 IU/L (both P < 0.001). On multivariate analysis, decreased pretreatment serum PChE levels were significantly associated with shorter OS (HR 0.553; 95 %CI 0.322-0.951; P = 0.032) and CSS (HR 0.484; 95 %CI 0.269-0.870; P = 0.015). CONCLUSIONS: Decreased pretreatment serum PChE level is an independent predictor for higher pT stage, shorter OS and CSS in patients with UTUC. Pretreatment serum PChE levels may act as a simple and effective parameter to predict prognosis for UTUC patients after RNU. PMID- 27554672 TI - Finite Element-Derived Surrogate Models of Locked Plate Fracture Fixation Biomechanics. AB - Internal fixation of bone fractures using plates and screws involves many choices implant type, material, sizes, and geometric configuration-made by the surgeon. These decisions can be important for providing adequate stability to promote healing and prevent implant mechanical failure. The purpose of this study was to develop mathematical models of the relationships between fracture fixation construct parameters and resulting 3D biomechanics, based on parametric computer simulations. Finite element models of hundreds of different locked plate fixation constructs for midshaft diaphyseal fractures were systematically assembled using custom algorithms, and axial, torsional, and bending loadings were simulated. Multivariate regression was used to fit response surface polynomial equations relating fixation design parameters to outputs including maximum implant stresses, axial and shear strain at the fracture site, and construct stiffness. Surrogate models with as little as three regressors showed good fitting (R 2 = 0.62-0.97). Inner working length was the strongest predictor of maximum plate and screw stresses, and a variety of quadratic and interaction terms influenced resulting biomechanics. The framework presented in this study can be applied to additional types of bone fractures to provide clinicians and implant designers with clinical insight, surgical optimization, and a comprehensive mathematical description of biomechanics. PMID- 27554673 TI - Dynamic Response and Residual Helmet Liner Crush Using Cadaver Heads and Standard Headforms. AB - Biomechanical headforms are used for helmet certification testing and reconstructing helmeted head impacts; however, their biofidelity and direct applicability to human head and helmet responses remain unclear. Dynamic responses of cadaver heads and three headforms and residual foam liner deformations were compared during motorcycle helmet impacts. Instrumented, helmeted heads/headforms were dropped onto the forehead region against an instrumented flat anvil at 75, 150, and 195 J. Helmets were CT scanned to quantify maximum liner crush depth and crush volume. General linear models were used to quantify the effect of head type and impact energy on linear acceleration, head injury criterion (HIC), force, maximum liner crush depth, and liner crush volume and regression models were used to quantify the relationship between acceleration and both maximum crush depth and crush volume. The cadaver heads generated larger peak accelerations than all three headforms, larger HICs than the International Organization for Standardization (ISO), larger forces than the Hybrid III and ISO, larger maximum crush depth than the ISO, and larger crush volumes than the DOT. These significant differences between the cadaver heads and headforms need to be accounted for when attempting to estimate an impact exposure using a helmet's residual crush depth or volume. PMID- 27554676 TI - What is the most effective treatment for frozen shoulder? PMID- 27554675 TI - Hypoglycemia During the Temporary Interruption of Parenteral Nutrition Infusion in Pediatric Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Parenteral nutrition (PN) is required with pediatric procedures such as hematopoietic stem cell transplantation (HSCT). However, risks associated with temporary PN infusion interruption remain unclear. MATERIALS AND METHODS: We retrospectively analyzed in 22 children undergoing HSCT receiving PN with the same daily routine: temporary PN infusion interruption before breakfast for administering a saline-diluted acyclovir drip. After correcting patients' glucose levels, we examined minimum blood glucose levels between preparative regimen initiation and post-HSCT day 30. Patients were divided into 2 groups according to a minimum glucose cutoff of 60 mg/dL. Patient background characteristics and hypoglycemia risk factors were compared between both groups. RESULTS: The hypoglycemia group had a significantly lower body surface area, higher glucose infusion rate (GIR), lower cholinesterase levels, and higher zinc levels at the onset of the minimum blood glucose level ( P < .05). Multivariate analyses revealed an association only between higher GIR (>=5 mg/kg/min) and hypoglycemia during the temporary PN infusion interruption. A time course analysis of blood glucose and immunoreactive insulin (IRI) levels in 1 patient revealed a combined high-caloric and saline flush before acyclovir initiation, causing temporary increased IRI, as the etiology for hypoglycemia. CONCLUSIONS: Particular attention and several precautions are required to prevent complications associated with temporary PN infusion interruption in children with higher GIR. PMID- 27554674 TI - Automated Gait Analysis Through Hues and Areas (AGATHA): A Method to Characterize the Spatiotemporal Pattern of Rat Gait. AB - While rodent gait analysis can quantify the behavioral consequences of disease, significant methodological differences exist between analysis platforms and little validation has been performed to understand or mitigate these sources of variance. By providing the algorithms used to quantify gait, open-source gait analysis software can be validated and used to explore methodological differences. Our group is introducing, for the first time, a fully-automated, open-source method for the characterization of rodent spatiotemporal gait patterns, termed Automated Gait Analysis Through Hues and Areas (AGATHA). This study describes how AGATHA identifies gait events, validates AGATHA relative to manual digitization methods, and utilizes AGATHA to detect gait compensations in orthopaedic and spinal cord injury models. To validate AGATHA against manual digitization, results from videos of rodent gait, recorded at 1000 frames per second (fps), were compared. To assess one common source of variance (the effects of video frame rate), these 1000 fps videos were re-sampled to mimic several lower fps and compared again. While spatial variables were indistinguishable between AGATHA and manual digitization, low video frame rates resulted in temporal errors for both methods. At frame rates over 125 fps, AGATHA achieved a comparable accuracy and precision to manual digitization for all gait variables. Moreover, AGATHA detected unique gait changes in each injury model. These data demonstrate AGATHA is an accurate and precise platform for the analysis of rodent spatiotemporal gait patterns. PMID- 27554677 TI - High-Throughput Screen for Inhibitors of Androgen Receptor-RUNX2 Transcriptional Regulation in Prostate Cancer. AB - Runt-related transcription factor 2 (RUNX2) plays a critical role in prostate cancer progression. RUNX2 interacts with the androgen receptor (AR) and modulates its transcriptional activity in a locus-specific manner. RUNX2 and AR synergistically stimulate a subset of genes, including the pro-oncogene snail family zinc finger 2 (SNAI2). AR-RUNX2 signaling cooperatively induces invasiveness of prostate cancer cells via SNAI2; and coexpression of AR, RUNX2, and SNAI2 in prostate cancer biopsy samples predicts disease recurrence. Competitive inhibition of AR alone could not disrupt the synergistic activation of SNAI2. We therefore established a phenotypic cell-based screening assay for compounds that could inhibit AR-RUNX2 synergistic activity either directly or indirectly. This assay was used to screen 880 compounds as a proof of concept, resulting in identification of several compounds that disrupted the synergistic stimulation of genes. Further investigation suggested the involvement of epidermal growth factor receptor (EGFR) signaling in AR/RUNX2 synergistic activity. Our assay is amenable to high-throughput screening and can be used to identify inhibitors of the AR-RUNX2 interaction in prostate cancer cells. PMID- 27554678 TI - Hydrogen-rich water regulates effects of ROS balance on morphology, growth and secondary metabolism via glutathione peroxidase in Ganoderma lucidum. AB - Ganoderma lucidum is one of the most important medicinal fungi, but the lack of basic study on the fungus has hindered the further development of its value. To investigate the roles of the redox system in G. lucidum, acetic acid (HAc) was applied as a reactive oxygen species (ROS) stress inducer, and hydrogen-rich water (HRW) was used to relieve the ROS stress in this study. Our results demonstrate that the treatment of 5% HRW significantly decreased the ROS content, maintained biomass and polar growth morphology of mycelium, and decreased secondary metabolism under HAc-induced oxidative stress. Furthermore, the roles of HRW were largely dependent on restoring the glutathione system under HAc stress in G. lucidum. To provide further evidence, we used two glutathione peroxidase (GPX)-defective strains, the gpxi strain, the mercaptosuccinic acid (MS, a GPX inhibitor)-treated wide-type (WT) strain, and gpx overexpression strains for further research. The results show that HRW was unable to relieve the HAc-induced ROS overproduction, decreased biomass, mycelium morphology change and increased secondary metabolism biosynthesis in the absence of GPX function. The gpx overexpression strains exhibited resistance to HAc-induced oxidative stress. Thus, we propose that HRW regulates morphology, growth and secondary metabolism via glutathione peroxidase under HAc stress in the fungus G. lucidum. Furthermore, our research also provides a method to study the ROS system in other fungi. PMID- 27554679 TI - Carbon Monoxide Potentiation of L-Type Ca2+ Channel Activity Increases HIF-1alpha Independent VEGF Expression via an AMPKalpha/SIRT1-Mediated PGC-1alpha/ERRalpha Axis. AB - AIMS: The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1alpha (HIF 1alpha)-dependent VEGF expression, the underlying mechanism independent of HIF 1alpha remains to be elucidated. RESULTS: HO-1 and VEGF were coexpressed in astrocytes of ischemic mouse brain tissues. Experiments with specific siRNAs and pharmacological activators/inhibitors of various target genes demonstrated that astrocytes pre-exposed to the CO-releasing compound, CORM-2, or transfected with HO-1 increased HIF-1alpha-independent VEGF expression via sequential activation of the following signal cascades; Ca2+/calmodulin-dependent protein kinase kinase beta-mediated AMP-activated protein kinase (AMPK)alpha activation, AMPKalpha induced increases in nicotinamide phosphoribosyltransferase (NAMPT) expression and cellular NAD+ level, sirtuin 1 (SIRT1)-dependent peroxisome proliferator activated receptor-gamma coactivator-1alpha (PGC-1alpha) stabilization and activation, and PGC-1alpha/estrogen-related receptor (ERR)alpha-mediated VEGF expression. All of these sequential events were blocked by an L-type voltage gated Ca2+ channel inhibitor and Ca2+ chelators, but not by other Ca2+ channel inhibitors. INNOVATION: HO-1-derived CO elicits Ca2+ influx by activating L-type Ca2+ channels, which is a key player in HIF-1alpha-independent VEGF expression by activating the AMPKalpha-NAMPT-SIRT1-PGC-1alpha/ERRalpha pathway. CONCLUSION: Our results provide new mechanistic insight into the possible role for L-type Ca2+ channels in HO-1/CO-induced angiogenesis. Antioxid. Redox Signal. 27, 21-36. PMID- 27554680 TI - Beral et al's 1990 paper on Kaposi's sarcoma among persons with AIDS: demonstrating the power of descriptive epidemiology. AB - Here we discuss the impact of Beral et al's 1990 paper "Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?" Not only did this paper galvanise research into the underlying infectious cause of Kaposi's sarcoma, it also demonstrated the power of observational epidemiology in pointing the way towards major discoveries. PMID- 27554682 TI - Semaphorins 4A and 4D in chronic inflammatory diseases. AB - Long-term inflammatory processes directed at a particular endogenous or exogenous antigen, or sometimes of unknown etiology, form the pathogenetic basis for many debilitating conditions, such as cardiovascular, pulmonary, autoimmune, neurologic diseases, and cancer. Recent discoveries of neuroimmune semaphorins 4A and 4D (Sema4A and Sema4D, respectively) expression and function in the immune system and their key regulatory roles in fine tuning of inflammatory processes made them the molecules of interest for a potential immunotherapy. In this short review, we discuss the current knowledge in the Sema4A and Sema4D actions in chronic inflammation underlying the outlined above diseases. PMID- 27554684 TI - The mechanobiology of wounds: The science of preventing pain and suffering. PMID- 27554685 TI - Erratum to 'Realistic glottal motion and airflow rate during human breathing'. [Medical Engineering & Physics, Volume 37, Issue 9, September 2015, Pages 829 839]. PMID- 27554683 TI - Potential dual role of nuclear factor-kappa B in experimental subarachnoid hemorrhage-induced early brain injury in rabbits. AB - OBJECTIVE AND DESIGN: Nuclear factor-kappa B (NF-kappaB) has multiple physiological and pathological functions. The role of NF-kappaB can be protective or destructive. We aim to investigate the biphasic activation of NF-kappaB in brain after subarachnoid hemorrhage (SAH). MATERIAL OR SUBJECTS: Eighty male New Zealand rabbits are assigned to control, SAH, vehicle, and pyrrolidine dithiocarbamate (PDTC) groups. TREATMENT: PDTC (3 mg/kg, dissolved in saline) was injected into cisterna magna. METHODS: Immunofluorescence and electrophoretic mobility shift assay experiments were performed to assess the activation of NF kappaB. The levels of inflammatory and apoptosis mediators were detected by ELISA and real-time polymerase chain reaction. Nissl and immunofluorescent stain was performed to evaluate neuron injury. RESULTS: NF-kappaB activity in the brain cortex showed two peaks after SAH. Inflammatory mediators exhibited similar time course. PDTC could significantly inhibit the NF-kappaB activity and inflammatory mediators. Suppressing the early NF-kappaB activity significantly decreased neuron injury, while inhibiting the late one could statistically increase neuron injury. CONCLUSIONS: The biphasic NF-kappaB activation in the brain cortex after SAH played a decisive role on neuronal fate through the inflammatory signaling pathway. The early NF-kappaB activity contributed to neuron damage after SAH. Nevertheless, the late activated NF-kappaB may serve as a protector. PMID- 27554686 TI - Increased Prevalence of Moderate and Severe Peripheral Arterial Disease in the American Indian (AI)/Alaskan Native (AN) Population; a Study of 96,000 AI/AN. AB - BACKGROUND: Peripheral arterial disease (PAD) disproportionally affects racial groups in the United States. Few studies have analyzed the rates of PAD in the American Indian (AI)/Alaskan Native (AN) population. In this article, we compare the prevalence of PAD in the AI/AN as compared with white and nonwhite Americans. METHODS: The study data were provided by Life Line Screening (Independence, OH). The cohort consists of self-referred individuals who paid for vascular screening tests. Mild-to-moderate and severe PAD were defined as having an ankle-brachial index (ABI) in at least one extremity of < 0.9 and < 0.5, respectively. Univariate and multivariate analyses were performed to compare the rates of PAD between AI/AN, Caucasians, and nonwhites. RESULTS: The original sample for which this study was obtained included 3,444,272 people. Of this group there was a predominance of females 64.5% (2,221,555) compared with 35.5% (1,222,716) males. The Native American/AN population was 2.8% of the sample (96,440). In our univariate analysis AI/AN had the highest rates of mild-moderate and severe PAD when compared with whites (odds ratio [OR] 1.78 and 2.14, respectively) and nonwhites (OR 1.52 and 1.82, respectively). We then controlled for atherosclerotic risk factors in our multivariate analysis, and the AI/NA cohort had persistently higher rates of both moderate and severe PAD compared with whites (OR 1.32 and 1.40) but not compared with nonwhites (OR 0.95 and 0.92). CONCLUSIONS: Here we present the largest epidemiology study of PAD in AI/AN to date. AI/NA people have disproportionately high rates of both mild to-moderate and severe PAD when compared with whites and nonwhite Americans. After controlling for atherosclerotic risk factors the rates of PAD remain high for AI/NA when compared with whites but not when compared with nonwhites. While it is possible that a combination of diet and lifestyle choices are responsible for the high rates of PAD in this population, genetic factors may be involved as well, and deserve further investigation. Optimal medical management may help to prevent the complications of PAD in this patient population. PMID- 27554687 TI - Hybrid Procedure with Debranching from the Descending Aorta for Aortic Arch Aneurysm after Previous Open Repair. AB - Aortic arch aneurysms can be treated with hybrid procedures by endovascular exclusion and prior debranching of supra-aortic arteries. We report on a case of symptomatic arch aneurysm following previous supracoronary ascending aorta and hemiarch replacement with a very short proximal landing zone. A successful reconstruction was performed by retrograde revascularization of supra-aortic vessels from the descending aorta and subsequent endovascular repair deploying a proximal stent graft directly above the sinotubular junction with good results in the 4-year follow-up. Retrograde supra-aortic debranching may constitute a suitable approach for hybrid endovascular repair of aneurysms of the aortic arch and the ascending aorta in selected cases. PMID- 27554688 TI - Real-World Performance of Paclitaxel Drug-Eluting Bare Metal Stenting (Zilver PTX) for the Treatment of Femoropopliteal Occlusive Disease. AB - BACKGROUND: The aim of this study was to evaluate the performance and predictors of stent failure of paclitaxel drug-eluting stents for the treatment of femoropopliteal disease. METHODS: A retrospective review of clinical and angiographic data was performed for patients treated for femoropopliteal disease with the Zilver PTX (Cook Medical, Bloomington, IN) stent by a single operator between 2012 and 2015 at a tertiary referral center. Clinical grading was determined by both Rutherford classification and the Society for Vascular Surgery's Wound, Ischemia, and Foot Infection (WIFi) scoring system, and lesions were classified anatomically by the TransAtlantic Intersociety Consensus (TASC) II criteria. Treated lesions included those with prior in-stent restenosis and long-segment disease. Primary clinical end points were stent failure, need for reintervention, and major adverse limb events (MALE). Kaplan-Meier methods and Cox proportional hazard models were used to evaluate factors affecting outcomes. RESULTS: Zilver PTX stents were placed in 52 limbs among 46 patients (71.1% male, mean age 72.6 years) with a median follow-up of 11.1 (range 1-26) months. Limbs were treated for life-disabling claudication in 76.9% and critical limb ischemia in 23.1%. Disease severity was highly variable, with 21 (40.4%) limbs with TASC C or D lesions and 16 (30.7%) treated for restenosis after prior endovascular treatment. During follow-up, 6 (12.7%) limbs experienced loss of stent patency (5 occlusions, one >50% restenosis). Four limbs underwent target lesion revascularization, 2 required open bypass, 2 underwent thrombolysis, and no patients required major amputation. Primary patency was 88.9%, 81.6%, and 81.6% at 6, 12, and 18 months, respectively. Treated lesion length (hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.14-21.75) was the only independent predictor of patency loss. Freedom from target lesion revascularization at 6, 12, and 18 months was 94.2%, 87.8%, and 87.8%, respectively. Freedom from MALE (composite of thrombolysis, major amputation, and bypass operation) was 97.5%, 90.9%, and 79.6% at 6, 12, and 18 months, respectively. Chronic renal insufficiency was the only factor that trended toward increased risk of MALE (HR 9.92, 95% CI 0.86-113.35) within a multivariate model. CONCLUSIONS: Our real-world experience supports the continued use of the Zilver PTX for the treatment of both de novo lesions and lesions with prior endovascular revascularization in the femoropopliteal segment. Routine follow-up between 6 and 12 months postoperatively is essential for detecting early restenosis and guiding reintervention. Careful attention when treating complex lesions and long-segment disease remains important for selecting the optimal revascularization strategy for individual patients and optimizing stent patency. PMID- 27554689 TI - Compression versus No Compression after Endovenous Ablation of the Great Saphenous Vein: A Randomized Controlled Trial. AB - BACKGROUND: The goal of this study is to determine if compression therapy after endovenous ablation (EVA) of the great saphenous vein (GSV) improves efficacy and patient-reported outcomes of pain, ecchymosis, and quality of life. METHODS: This is a prospective randomized controlled trial from 2009 to 2013 comparing the use of thigh-high 30-40 mm Hg compression therapy for 7 days versus no compression therapy following EVA of the GSV. Severity of venous disease was measured by clinical severity, etiology, anatomy, pathophysiology scale and the Venous Clinical Severity Score (VCSS). Quality of life assessments were carried out with a Chronic Venous Insufficiency Questionnaire (CIVIQ-2) at days 1, 7, 14, 30, and 90, and the Visual Analog Pain Scale daily for the first week. Bruising score was assessed at 1 week post procedure. Postablation venous duplex was also performed. RESULTS: Seventy patients and 85 limbs with EVA were randomized. EVA modalities included radiofrequency ablation (91%) and laser ablation (9%). Clinical severity, etiology, anatomy, pathophysiology class and VCSS scores were equivalent between the 2 groups. There was no significant difference in patient reported outcomes of postprocedural pain scores at day 1 (mean 3.0 vs. 3.12, P = 0.948) and day 7 (mean 2.11 vs. 2.81, P = 0.147), CIVIQ-2 scores at 1 week (mean 36.9 vs. 35.1, P = 0.594) and 90 days (mean 29.1 vs. 22.5, P = 0.367), and bruising score (mean 1.2 vs. 1.4, P = 0.561) in the compression versus no compression groups, respectively. Additionally, there was a 100% rate of GSV closure in both groups and no endothermal heat-induced thrombosis as assessed by postablation duplex. CONCLUSIONS: Compression therapy does not significantly affect both patient-reported and clinical outcomes after GSV ablation in patients with nonulcerated venous insufficiency. It may be an unnecessary adjunct following GSV ablation. PMID- 27554690 TI - Adductor Canal Compression Syndrome in a 46-Year-Old Female Patient Leading to Acute External Iliac, Femoral, and Popliteal Artery Thrombosis and Critical Ischemia: A Case Report. AB - The adductor canal compression syndrome is one of the several rare nontraumatic causes of arterial occlusions, which may lead to critical ischemia of the lower limb. We report the case of a 46-year-old athletic woman, who suffered from activity-related paresthesia and sharp pain in the left upper and lower leg for 2 years. Imaging and neurological investigations of the spine remained without pathological findings that would explain the patient's complaints. Actually, the patient presented with symptoms of critical lower limb ischemia. Magnetic resonance angiography revealed nearly complete thrombotic occlusion of the common femoral artery and the arteries of the lower leg. An emergency surgery was performed, revealing an external compression of the superficial femoral artery in the adductor canal. Subsequently, a thrombectomy was performed and a venous bypass graft was installed. No postoperative complications occurred, the patient recovered well and could return to her activities of daily living about 3 weeks after the surgery. The adductor canal compression syndrome results from a local anomalous musculotendinous band or hypertrophic musculature surrounding the passing structures. It mainly occurs in athletes exposed to repetitive stress, especially runners and skiers, and may lead to thrombosis followed by critical lower extremity ischemia. The lack of obvious symptoms during routine physical examination often impedes rapid diagnosis and timely therapy. Considering the high thrombotic risk, attention should be paid to this rare cause of lower limb pain to prevent the patient from critical lower extremity ischemia and potential limb loss due to consecutive acute thrombotic occlusions. PMID- 27554691 TI - Modifiable Factors Leading to Increased Length of Stay after Carotid Endarterectomy. AB - BACKGROUND: Carotid endarterectomy (CEA) is a commonly performed vascular operation. Yet, postoperative length of stay (LOS) varies greatly even within institutions. In this study, the morbidity and mortality, as well as financial impact of increased LOS were reviewed to establish modifiable factors associated with prolonged hospital stay. METHODS: The Society for Vascular Surgery Vascular Quality Initiative database was used to identify all patients undergoing primary CEA at a single institution between June 1, 2011 and November 28, 2014. Preoperative patient characteristics, intraoperative details, postoperative factors, long-term outcomes, and cost data were reviewed using an Institutional Review Board-approved prospectively collected database. Multivariate analysis was used to determine statistical difference between patients with LOS <=1 day and >1 day. RESULTS: Complete 30-day variable and cost data were available for 219 patients with an average follow-up of 12 months. Seventy-nine (36%) patients had an LOS > 1 day. Variables determined to be statistically significant predictors of prolonged LOS included preoperative creatinine (P = 0.02) and severe congestive heart failure (P = 0.05) with self-pay status (P = 0.02) and preoperative beta-blocker therapy (P = 0.04) being protective. Shunt placement (P = 0.04), arterial re-exploration, and postoperative cardiac (P = 0.001) or neurological (P = 0.03) complications also resulted in prolonged hospitalization. Specific modifiable risk factors that contributed to increased LOS included operative start time after noon (P = 0.04), drain placement (P = 0.05), prolonged operative time (101 vs. 125 min, P = 0.01), return to the operating room (P = 0.01), and postoperative hypertension (P = 0.02) or hypotension (P = 0.04). Of note, there was no difference in LOS associated with technique (conventional versus eversion), patch use (P = 0.49), protamine administration (P = 0.60), electroencephalogram monitoring (P = 0.45), measurement of stump pressure (P = 0.63), Doppler (P = 0.36), or duplex (P = 0.92). Both hospital charges (P = 0.0001) and costs (P = 0.0001) were found to be significantly higher in patients with prolonged LOS, with no difference in physician charges (P = 0.10). Increased LOS after CEA was associated with an increase in 12-month mortality (P = 0.05). CONCLUSIONS: Increased LOS was associated with increased hospital charges, costs, as well as significant morbidity and midterm mortality following CEA. Furthermore, this study highlights several modifiable risk factors leading to increased LOS. Identified factors associated with increase LOS can serve as targets for improving care in vascular surgery. PMID- 27554692 TI - Analysis of Compensation Disparities between Junior Academic and Private Practice Vascular Surgeons. AB - BACKGROUND: Compensation may be a significant factor for academic vascular surgeons seeking or changing employment. We compared compensation for academic and private practice vascular surgeons practicing for approximately similar duration. METHODS: Compensation data for academic and private practice vascular surgeons were obtained from the Association of American Medical Colleges (AAMC) and Medical Group Management Association (MGMA), respectively. Comparisons of nominal annual compensation data were made between Group 1 (assistant professor vascular surgeons versus private practice vascular surgeons in practice for 1-7 years), Group 2 (associate professor vascular surgeons versus private practice vascular surgeons in practice for 8-17 years), and Group 3 (professor vascular surgeons versus private practice vascular surgeons in practice for >=18 years) from 2003 to 2012. RESULTS: In Group 1, there was a $54,500 difference in 2003 (P = 0.043) which increased to $110,500 by 2012 (P = 0.001). In Group 2, there was a $44,200 difference in 2007 (P = 0.016) which increased to $53,400 by 2010 (P = 0.034). In Group 3, there was no statistically significant difference in compensation (P >= 0.999). CONCLUSIONS: There is a significant and increasing disparity in compensation in favor of private practice vascular surgeons compared with assistant professor vascular surgeon faculty. Differences equalized with increasing seniority and experience. Compensation plans should be market based and in line with nonacademic benchmarks as well. PMID- 27554693 TI - Multidisciplinary Management of Blunt Renal Artery Injury with Endovascular Therapy in the Setting of Polytrauma: A Case Report and Review of the Literature. AB - BACKGROUND: Injury to the renal artery is a rare but serious concern in patients suffering blunt trauma. Complications of renovascular injury include prolonged hospitalization, kidney loss, and death. There remains considerable controversy regarding the optimal treatment of blunt renal artery injury. METHODS: We describe the management of a 39-year-old woman following blunt polytrauma who underwent a multidisciplinary collaborative procedure with open splenectomy and endovascular repair of an occluded renal artery. A literature review of the past 25 years follows including all publications describing endovascular treatment for blunt renal artery injury. RESULTS: The literature search identified 27 patients with blunt renal artery injury treated by endovascular means. All patients were treated with angioplasty and stenting; none were treated with angioplasty alone. One patient (4%) required nephrectomy for hypertension and 89% of patients were reported to be in good condition at their last contact with the healthcare system. CONCLUSIONS: The optimal treatment of blunt injury to the renal artery is unknown, but endovascular therapy is a feasible and reasonable choice. Further study is warranted to delineate the appropriate role for endovascular treatment as a component of a multidisciplinary approach to the care of trauma patients with blunt renal artery injury. PMID- 27554694 TI - Medicare Facility Diagnosis-Related Groups Have Outpaced Individual Physician Payment. AB - BACKGROUND: We set out to compare the rates of Medicare reimbursement to physicians versus hospitals for several major vascular procedures over a period of 5 years. METHODS: We queried the Wolters Kluwer MediRegs database to collect Medicare reimbursement data from fiscal years 2011 to 2015. We surveyed reimbursements for carotid endarterectomy, carotid angioplasty and stenting, femoropopliteal bypass, and lower extremity fem-pop revascularization with stenting. Based on data availability, we surveyed physician reimbursement data on the national level and in both medically overserved and underserved areas. Hospital reimbursement rates were examined on a national level and by hospitals' teaching and wage index statuses. RESULTS: We found that for all 4 vascular procedures, Medicare reimbursements to hospitals increased by a greater percentage than to physicians. By region, underserved areas had lower physician reimbursements than the national average, while the opposite was true for overserved areas. Additionally, for hospital Medicare reimbursements, location in a high wage index accounted for a significant increase in reimbursement over the national average, with teaching status contributing to this increase in a smaller extent. CONCLUSIONS: These data on Medicare reimbursements indicate that payments to hospitals are increasing more significantly than to physicians. This disparity in pay changes affects both independent and academic vascular surgeons. Medicare should consider pay increases to independent providers in accordance to the hospital pay increase. PMID- 27554695 TI - The Need for Accreditation of Office-Based Interventional Vascular Centers. AB - The rise in office-based interventional vascular laboratories in recent years was prompted in part by expedient ambulatory patient experience and favorable outpatient procedural reimbursement. While studies have shown that clinical safety and treatment efficacy can be achieved in office-based vascular facilities, critics have raised various concerns due to inconsistent patient care standards and lack of organizational oversight to ensure optimal patient outcome. Available literature showed widely varied clinical outcomes which were partly attributable to nonuniform standards in reporting clinical efficacy and adverse events. In this report, various concerns and pitfalls of office-based interventional vascular centers are discussed. Strategies to improve patient care delivery in office-based laboratories including accreditations which serve as external validation of processes to ensure patient care and safety are also mentioned. Finally, the requirements to obtain accreditation in an office-based practice and the differences between these nationally recognized accrediting organizations are discussed herein. PMID- 27554696 TI - Use of Self-Expanding Covered Stents as Bailout Treatment of Spontaneous Rupture of the Femoral Artery Caused by Staphylococcus aureus Infection. AB - Spontaneous rupture of femoropopliteal arteries caused by infection requires treatment in the urgent setting. The present article reports on the performance of self-expanding covered stents in 3 patients who experienced acute rupture of the femoral artery caused by Staphylococcus aureus infection. After a mean follow up of 16.4 months, the bailout placement of self-expanding covered devices showed sustained patency and sufficient exclusion of the rupture site. A surgical conversion and bypass reconstruction was not necessary. Long-term follow-up and inclusion of more patients are needed to provide more evidence about the utility of this approach. PMID- 27554697 TI - Embolization of Onyx Causing Acute Limb Ischemia. AB - We present the case of a patient with a refractory type II endoleak treated with translumbar Onyx with passage of the Onyx material into the endograft and subsequent embolization to the infrainguinal vasculature. This report represents a new complication of Onyx embolization that, to our knowledge, has not previously been described in the literature. PMID- 27554698 TI - Hybrid Treatment for Budd-Chiari Syndrome: A Case Report by 11-Year Follow-up. AB - Budd-Chiari syndrome (BCS) is a rare hepatic disease caused by occlusion of the hepatic venous outflow at any level from the small hepatic veins to the atriocava junction. BCS could have serious consequences if not treated promptly. The appropriate therapeutic strategy can be offered to change the natural course of the disease. The present case reports a young man with BCS who successfully received the hybrid treatment combined with endovascular intervention and mesocaval shunt by step. The 11-year follow-up showed that the patient was free of clinical symptoms, and computed tomography and ultrasonography confirmed the patency of the stent and shunt. Although BCS therapy methods are well established, the patient often needs to be treated repeatedly because of the high risk of recurrence. Step therapeutic strategy to alleviate portal and inferior vena cava hypertension of BCS patients are respected. The combination of endovascular intervention and mesocaval shunt was effective in our patient, and both stent and shunt have satisfactory long-term patency. PMID- 27554699 TI - Long-Term Effect of the Type of Carotid Endarterectomy on Blood Pressure. AB - BACKGROUND: The dissection of the carotid sinus nerve in eversion carotid endarterectomy (eCEA) has been hypothesized to cause an increase in postoperative blood pressure (BP). The objective of this study is to evaluate the effect of eCEA on BP and changes in BP medications over the course of year-long follow-up after eCEA compared with longitudinal incision carotid endarterectomy patch angioplasty (pCEA). METHODS: A retrospective review of patients who underwent CEA between July 1, 2009 and June 30, 2014 in the Vascular Surgery Department at The University of Iowa Hospital and Clinics was conducted. Demographics, comorbidities, BP, and number, dosage, and type of antihypertensive medications were collected preoperatively, at 30 days, and at 12 months. The differences in BP and medications between pCEA and eCEA patients were compared. Demographic data and comorbidities were compared using t-tests and chi-squared analysis. Differences in BP and medication dosages were analyzed using multivariate analysis of variance. RESULTS: In total, 363 CEA procedures were performed during the study period, of which 275 procedures were included in the final analysis. Thirty percent of the patients underwent eCEA. Fifty-four percent of the patients who underwent eCEA and 60% of the patients who underwent pCEA were symptomatic. Thirty-day mortality was 1.4% and 12-month mortality was 6.4% for the entire population. No postoperative neurologic deficits, including stroke, were observed. Analysis of BP did not yield a significant difference among preoperative, 30-day, and 12-month follow-up measurements (P = 0.893). There was no significant change to the number and total daily dose of BP medications preoperatively, at 30 days, or at 12 months. CONCLUSIONS: There is no statistical difference in mortality, morbidity, and patency rates at 30 days and 12 months between pCEA and eCEA. eCEA is also not associated with long-term BP changes compared with pCEA. PMID- 27554700 TI - A Cost Analysis of Regional Versus General Anesthesia for Carotid Endarterectomy. AB - BACKGROUND: Medical care in the United States has evolved into a more cost conscious value-based health care system that necessitates a comparison of costs when there are alternative interventions considered to be acceptable in the treatment of a disease. This study compares the cost differences between regional anesthesia (RA) and general anesthesia (GA) for carotid endarterectomy (CEA). METHODS: Data from 346 consecutive patients who underwent CEA between January 2012 and September 2014 were retrospectively reviewed for the type of anesthesia used, outcomes data, and cost variables. Overall hospital day costs were compared between RA and GA. Medians and interquartile ranges were compared using Wilcoxon Mann-Whitney test. A P < 0.05 was considered statistically significant using 2 sided tests. RESULTS: Median overall costs for GA were significantly higher than median costs for RA (medians [with interquartile ranges], $10,140 [$7,158 $12,658] versus $7,122 [$5,072-$8,511], P < 0.001). Median total operative time for GA was significantly longer than median time for RA (168 [144-188] versus 134 [115-147] min, P < 0.001). Median in-hospital length of stay (LOS) for GA was significantly longer compared with RA (2.0 vs 1.2 days, P < 0.001). Patients who received GA were also more likely to be admitted to the intensive care unit. CONCLUSIONS: Decreased cost, operating room expenses, postoperative resources, and overall LOS were observed for individuals who underwent RA for CEA as compared with GA. In summary, RA is more cost-effective and should be the optimal choice when clinically appropriate. PMID- 27554701 TI - Endovascular Management of Concomitant Thoracic and Abdominal Aortic Ruptures Resulting from Brucellosis Aortitis. AB - BACKGROUND: Acute aortic symptomatology is an unusual manifestation of Brucella melitensis infection. We present a rare case of acute multifocal thoracic and abdominal aortic ruptures arising from Brucellosis aortitis managed exclusively with endovascular surgery. METHODS: A 71-year-old Hispanic male with a history of atrial fibrillation and prior stroke on chronic anticoagulation presented with shortness of breath and malaise. In addition, he had been treated approximately 1 year previously in Mexico for B. melitensis bacteremia after eating fresh unpasteurized cheese. Computed tomography (CT) angiography demonstrated an acute rupture of the descending thoracic aorta just proximal to the celiac trunk and synchronous rupture at the abdominal aortic bifurctation. RESULTS: The patient was taken emergently to the hybrid operating room, where synchronous supraceliac thoracic aorta and abdominal aortoiliac stent grafts were deployed under local anesthesia. Completion angiography demonstrated total exclusion of the thoracic and abdominal extravasation with no evidence of endoleak. Twenty hours postoperatively, the patient became acutely obtunded and hypotensive. Repeat CT angiography demonstrated contrast extravasation at the level of the excluded aortic bifurcation. Emergent angiography confirmed a type II endoleak with free extraluminal rupture. Multiple coils were placed at the level of the aortic bifurcation between the left limb of the stent graft and the aortic wall to tamponade the endoleak. No further extravasation was noted on final aortography. Postoperatively, blood cultures confirmed the diagnosis of B. melitensis. The patient was treated with systemic doxycycline, gentamicin, and rifampin. Resolution of the acute event occurred without additional sequelae and he was discharged from the hospital to a rehabilitation facility. CONCLUSIONS: Concomitant multifocal aortic ruptures arising from Brucellosis aortic infection is a very rare event. In this case, the patient was successfully treated with thoracic and abdominal endovascular stent-graft exclusion, coiling, and long-term targeted antibiotics. PMID- 27554702 TI - Mothers' education and working status; do they contribute to corrosive poisoning among paediatric patients of Karachi, Pakistan? AB - OBJECTIVE: To determine the causative factors behind corrosive poisoning in children like effect of working mothers, their educational status, financial background, family size and number of siblings. METHODS: The multi-centre, prospective, case series of all paediatric patients presenting to the Emergency Department of the National Institute of Child Health and the Aga Khan University Hospital, Karachi from August 2008 to July 2009 is presented. It comprised all paediatric patients with a history of corrosive poisoning at the two hospitals. SPSS 20 was used for statistical analysis. RESULTS: Out of 105 cases, 56(53%) related to the private-sector Aga Khan University Hospital, and 49(47%) to the public-sector National Institute of Child Health. Of the total, 82(78%) were in 1 5 age group; 61 (58%) were males; and 44(42%) were females. While 59 (56.2%) mothers were educated, only 21 (20%) were working. Of the 46 (43.8%) non-educated mothers, 20 (19%) were working. The type of poison was alkali in 81(77%) cases, acid in 23(22%). The corrosive varied from liquid in 80(76%) cases to powder/gel/semi-solid form in 25(24%) exposures. Besides, 65 (61.9%) families had 3 or more siblings, and the age of siblings was less than 10 in 60 (57.14%) cases, In 34 (32.38%) cases, the chemical were kept in the original container, while in 71 (67.61%) cases other commonly used and familiar containers were used to store these chemicals. Kitchen was the most common place with 51 (48.57%) cases. The time of incident was afternoon in 51(48.57%) cases. Majority cases (n=23; 21.9%) occurred in October. CONCLUSIONS: There are multiple contributory factors in corrosive exposure among children rather than the mother's working status and her educational background. PMID- 27554703 TI - The utility of genetic testing in neuromuscular disease: A consensus statement from the AANEM on the clinical utility of genetic testing in diagnosis of neuromuscular disease. AB - INTRODUCTION: The aim of this consensus statement is to provide a recommendation from AANEM experts on the clinical utility of genetic testing. It is not meant to recommend or endorse any specific genetic testing methodology or algorithm. METHODS: The AANEM Professional Practice Committee reached a consensus based on expert opinion on the utility of genetic testing in neuromuscular diseases and made recommendations on factors that physicians and patients should consider when deciding whether to proceed with such testing. RESULTS: Despite the costs of genetic testing, these tests can be both valuable and beneficial in the diagnosis and treatment of neuromuscular diseases in many situations. CONCLUSIONS: The AANEM believes that performing genetic testing to arrive at a specific molecular diagnosis is a critical step in providing high-quality care to neuromuscular patients. The cost of testing should not be a deterrent, as there are important clinical, safety, psychosocial, and research benefits. Muscle Nerve 54: 1007 1009, 2016. PMID- 27554704 TI - An Evaluation of a Smartphone-Assisted Behavioral Weight Control Intervention for Adolescents: Pilot Study. AB - BACKGROUND: The efficacy of adolescent weight control treatments is modest, and effective treatments are costly and are not widely available. Smartphones may be an effective method for delivering critical components of behavioral weight control treatment including behavioral self-monitoring. OBJECTIVE: To examine the efficacy and acceptability of a smartphone assisted adolescent behavioral weight control intervention. METHODS: A total of 16 overweight or obese adolescents (mean age=14.29 years, standard deviation=1.12) received 12 weeks of combined treatment that consisted of weekly in-person group behavioral weight control treatment sessions plus smartphone self-monitoring and daily text messaging. Subsequently they received 12 weeks of electronic-only intervention, totaling 24 weeks of intervention. RESULTS: On average, participants attained modest but significant reductions in body mass index standard score (zBMI: 0.08 standard deviation units, t (13)=2.22, P=.04, d=0.63) over the in-person plus electronic only intervention period but did not maintain treatment gains over the electronic only intervention period. Participants self-monitored on approximately half of combined intervention days but less than 20% of electronic-only intervention days. CONCLUSIONS: Smartphones likely hold promise as a component of adolescent weight control interventions but they may be less effective in helping adolescents maintain treatment gains after intensive interventions. PMID- 27554705 TI - Radon in the soil air of Estonia. AB - Several investigations in Estonia during 1996!-1999 have shown that permissible level (200 Bq/m3) of radon (222Rn) in indoor air is exceeded in 33% of the inspected dwellings. This makes Estonia one of the five countries with highest radon risk in Europe (Fig 1). Due to correlation between the soil radon risk level and radon concentration in houses, small scale radon risk mapping of soil air was carried out (one study point per 70-100 km2). It turned out that one third of Estonian mainland has high radon risk potential, where radon concentration in soil air exceeds safe limit of 50 kBq/m3. In order to estimate radon content in soil air, two different methods developed in Sweden were used simultaneously. Besides measuring radon content from soil air at the depth of 80 cm with an emanometer (RnM), maximum potential content of radon in soil (RnG) was estimated based on the rate of eU (226Ra) concentration in soil, which was acquired by using gamma-ray spectrometer. Mapping and following studies revealed that simultaneously measured RnG and RnM in study points may often differ. To inspect the cause, several monitoring points were set up in places with different geological conditions. It appeared that unlike the RnG content, which remains close to average level in repeated measurements, the RnM content may differ more than three times periodically. After continuous observations it turned out that concentration of directly measured radon depended on various factors being mostly controlled by mineral composition of soil, properties of topsoil as well as different factors influencing aeration of soil. The results of Rn monitoring show that reliable level of radon risk in Estonian soils can only be acquired by using calculated Rn-concentration in soil air based on eU content and directly measured radon content of soil air in combination with interpreting specific geological and geochemical situations in the study points. PMID- 27554706 TI - The uncertainty in the radon hazard classification of areas as a function of the number of measurements. AB - The administration in many countries demands a classification of areas concerning their radon risk taking into account the requirements of the EU Basic Safety Standards. The wide variation of indoor radon concentrations in an area which is caused by different house construction, different living style and different geological situations introduces large uncertainties for any classification scheme. Therefore, it is of importance to estimate the size of the experimental coefficient of variation (relative standard deviation) of the parameter which is used to classify an area. Besides the time period of measurement it is the number of measurements which strongly influences this uncertainty and it is important to find a compromise between the economic possibilities and the needed confidence level. Some countries do not use pure measurement results for the classification of areas but use derived quantities, usually called radon potential, which should reduce the influence of house construction, living style etc. and should rather represent the geological situation of an area. Here, radon indoor measurements in nearly all homes in three municipalities and its conversion into a radon potential were used to determine the uncertainty of the mean radon potential of an area as a function of the number of investigated homes. It could be shown that the coefficient of variation scales like 1/?n with n the number of measured dwellings. The question how to deal with uncertainties when using a classification scheme for the radon risk is discussed and a general procedure is proposed. PMID- 27554707 TI - Radon measurements in an area of tectonic zone: A case study in Central Slovakia. AB - General overviews of the spatial distribution of radon and other natural radionuclides in the geological basement as commonly presented on regional or country maps tend to offer a low density of information, insufficient for gaining relevant knowledge of the environmental impact, especially in the areas of tectonic zones often assumed to be radon prone and therefore dangerous for the human population. An additional survey, employing radon measurements in soil and indoor air, was carried out seeking to provide a more detailed characterization of the expressive fault zone of the Mala Magura in the Horna Nitra region of Central Slovakia. Eventually, the results of soil 222Rn volume activity measurements along two short profiles crossing the assumed fault line did not reveal any indication of active nature of local tectonics, but merely pointed to an existence of a zone of contact between different types of rocks. The results of indoor radon measurements in dwellings of two villages lying on the studied fault showed values that were lower than those commonly observed on the Slovak territory, ruling out any negative health impact on population. Nevertheless, in order to add new findings to an already well established study of geological structure of the region, the indoor radon data collected through a previous survey require a further analysis. PMID- 27554708 TI - Radiological characterization and evaluation of high volume bauxite residue alkali activated concretes. AB - Bauxite residue, also known as red mud, can be used as an aggregate in concrete products. The study involves the radiological characterization of different types of concretes containing bauxite residue from Ukraine. The activity concentrations of radionuclides from the 238U, 232Th decay series and 40K were determined for concrete mixture samples incorporating 30, 40, 50, 60, 75, 85 and 90% (by mass) of bauxite residue using gamma-ray spectrometry with a HPGe detector. The studied bauxite residue can, from a radiological point of view using activity concentration indexes developed by Markkanen, be used in concrete for building materials and in road construction, even in percentages reaching 90% (by mass). However, when also occupational exposure is considered it is recommended to incorporate less than 75% (by mass) of Ukrainian bauxite residue during the construction of buildings in order to keep the dose to workers below the dose criterion used by Radiation Protection (RP) 122 (0.3 mSv/a). Considering RP122 for evaluation of the total effective dose to workers no restrictions are required for the use of the Ukrainian bauxite residue in road construction. PMID- 27554755 TI - Progressive MS Alliance Industry Forum: Maximizing Collective Impact To Enable Drug Development. AB - The Progressive MS Alliance Industry Forum describes a new approach to address barriers to developing treatments for progressive multiple sclerosis (MS). This innovative model promises to facilitate robust collaboration between industry, academia, and patient organizations and accelerate research towards the overarching goal of developing safe and effective treatments for progressive MS. PMID- 27554756 TI - Pediatric malignant germ cell tumors: A comparison of the neuro-oncology and solid tumor experience. AB - Malignant germ cell tumors (GCT) arise from abnormal migration of primordial germ cells and are histologically identical whether they occur inside or outside the central nervous system (CNS). However, the treatment strategy for GCTs varies greatly depending on the location of the tumor. These differences are in part due to the increased morbidity of surgery in the CNS but may also reflect differential sensitivity of the tumors to chemotherapy and radiation therapy (RT) or not-yet-understood biologic differences between these tumors. Historically, specialists caring for extracranial and intracranial GCT in the United States have practiced separately without much cross communication. The focus of this review is a discussion of differences between the management of CNS and extra-CNS GCTs and opportunities for collaboration and future research. PMID- 27554757 TI - Identification of a novel HLA-A*02 variant, HLA-A*02:621, in a Taiwanese bone marrow donor. AB - One nucleotide replacement at residue 169 of HLA-A*02:01:01:01 results in a new allele, HLA-A*02:621. PMID- 27554758 TI - Planthopper family Issidae (Insecta: Hemiptera: Fulgoromorpha): linking molecular phylogeny with classification. AB - A molecular phylogeny of the planthopper family Issidae (Hemiptera, Fulgoroidea) is provided using both Maximum likelihood and Bayesian inference analyses. The phylogeny is based on 18S, two parts of 28S, COXI and Cytb genes from 50 genera and 79 ingroup species (including 8 species recently excluded from Issidae). As with the only few previous studies, an important taxonomic impediment is observed with the sampling; however for the first time, all analyses depict several fully supported lineages, which challenge the recent proposed "modern classification" of the family. It also highlights a strong coherence between these lineages and their respective geographical distribution. All previously excluded taxa are confirmed as not being part of the Issidae as recently defined which monophyly is confirmed. Accordingly, a new classification of the family is proposed with 3 subfamilies and 7 tribes as follows. Neotropical issid Thioniini in Thioniinae stat. rev. is re-established as an independent lineage sister to all other Issidae. Palaearctic Issidae are weakly supported as a monophyletic lineage, Issinae stat. nov., including 2 tribes: Issini stat. nov. (genera Issus and Latissus) and Hysteropterini stat. rev. (all other Palaearctic genera). Oriental Issidae form a strongly supported monophyletic subfamily group Hemisphaeriinae stat. rev. including 4 tribes: Kodaianellini trib. nov., Sarimini trib. nov., Parahiraciini Cheng & Yang, 1991, and Hemisphaeriini Melichar, 1906, the latter including 2 subtribes: Mongolianina s.trib. nov., and Hemisphaeriina Melichar, 1906. A Neotropical lineage including the genus Picumna is provisionally placed in incertae sedis within the Hemisphaeriinae stat. nov. PMID- 27554759 TI - Evolutionary history of chloridoid grasses estimated from 122 nuclear loci. AB - Chloridoideae (chloridoid grasses) are a subfamily of ca. 1700 species with high diversity in arid habitats. Until now, their evolutionary relationships have primarily been studied with DNA sequences from the chloroplast, a maternally inherited organelle. Next-generation sequencing is able to efficiently recover large numbers of nuclear loci that can then be used to estimate the species phylogeny based upon bi-parentally inherited data. We sought to test our chloroplast-based hypotheses of relationships among chloridoid species with 122 nuclear loci generated through targeted-enrichment next-generation sequencing, sometimes referred to as hyb-seq. We targeted putative single-copy housekeeping genes, as well as genes that have been implicated in traits characteristic of, or particularly labile in, chloridoids: e.g., drought and salt tolerance. We recovered ca. 70% of the targeted loci (122 of 177 loci) in all 47 species sequenced using hyb-seq. We then analyzed the nuclear loci with Bayesian and coalescent methods and the resulting phylogeny resolves relationships between the four chloridoid tribes. Several novel findings with this data were: the sister lineage to Chloridoideae is unresolved; Centropodia+Ellisochloa are excluded from Chloridoideae in phylogenetic estimates using a coalescent model; Sporobolus subtilis is more closely related to Eragrostis than to other species of Sporobolus; and Tragus is more closely related to Chloris and relatives than to a lineage of mainly New World species. Relationships in Cynodonteae in the nuclear phylogeny are quite different from chloroplast estimates, but were not robust to changes in the method of phylogenetic analysis. We tested the data signal with several partition schemes, a concatenation analysis, and tests of alternative hypotheses to assess our confidence in this new, nuclear estimate of evolutionary relationships. Our work provides markers and a framework for additional phylogenetic studies that sample more densely within chloridoid tribes. These results represent progress towards a robust classification of this important subfamily of grasses, as well as proof-of-concept for hyb-seq next-generation sequencing as a method to generate sequences for phylogenetic analyses in grasses and other plant families. PMID- 27554760 TI - Metabolic blood profile of beef heifers during oestrous and non-oestrous states. AB - Haematological metabolic profiles in heifers could contribute to the development of proxies for oestrous detection and provide clues to further characterize biological changes during oestrus. One hundred and seven beef heifers were observed for oestrous behaviour twice daily for 124 days. Feed intake and productive performance (body weight and composition) traits were measured, and feed efficiency was determined using residual feed intake (kg DM/day). Blood plasma samples were collected when signs of oestrus were observed and every 30 +/ 2 days. Heifers were considered in oestrus (n = 71) when plasma progesterone concentrations were <0.6 ng/ml. Least square means of blood metabolic parameters were compared between oestrous and non-oestrous states and within oestrous groups according to performance traits and age. Heifers in oestrus exhibited higher concentrations of alkaline phosphatase, aspartate aminotransferase (AST), beta hydroxybutyric acid, creatine kinase (CK) and triiodothyronine (T3) than heifers in non-oestrus. Heifers in oestrus revealed lower osmolality and concentrations of calcium, sodium and total protein than during non-oestrus. Younger (and smaller) heifers had greater concentrations of CK, gamma-glutamyl transferase (GGT), glucose and sodium than the older heifers. Heifers with lower fatness had increased osmolality and concentrations of cholesterol, CK, phosphorus, sodium and reduced T3 levels. Feed efficient heifers had greater levels of AST, cholesterol and GGT than inefficient heifers. Blood plasma parameters may be complementary to oestrous detection upon further validation; effects of age, feed efficiency, body size and body composition should be considered to optimize this haematological assessment. PMID- 27554761 TI - Data Resource Profile: The Human Fertility Database. PMID- 27554762 TI - Nomenclature of homodetic cyclic peptides produced from ribosomal precursors: An IUPAC task group interim report. AB - In 2015, an International Union of Pure and Applied Chemistry (IUPAC) Task Group was formed to develop nomenclature recommendations for homodetic cyclic peptides produced from ribosomal precursors. Delegates of the 2015 International Conference on Circular Proteins (ICCP) were presented with the strengths and weaknesses of four published approaches to homodetic cyclic peptide nomenclature, and a summary of the ensuing discussion is presented here. This interim report presents a potentially novel suggestion-the use of Cahn-Ingold-Prelog rules to specify amino acid priority in homodetic peptides for consistent numbering. Indeed, this might be the first extension of the Cahn-Ingold-Prelog rules in five decades. The authors invite interested parties to contact the corresponding author with suggestions for the improvement of the proposed nomenclature; these ideas will be discussed and considered for inclusion in the final report. PMID- 27554764 TI - The preventive effects of two nutraceuticals on experimentally induced acute synovitis. AB - BACKGROUND: Nutraceuticals are often used in the management of equine osteoarthritis, but scientific evidence of their efficacy is lacking. OBJECTIVES: To study the preventive effects of two new nutraceuticals after the experimental induction of synovitis in comparison with positive and negative control treatments. STUDY DESIGN: Blinded, controlled, randomised experiment. METHODS: Twenty-four healthy Standardbred horses were randomly allocated to supplement AT (multi-ingredient, 28 days), supplement HP (collagen hydrolysate, 60 days), meloxicam (4 days) or placebo (60 days). Synovitis was induced in the right intercarpal joint by intra-articular injection of 0.5 ng lipopolysaccharide (LPS) of Escherichia coli while treatments were continued. Blood and synovial fluid were sampled before treatment, immediately prior to LPS injection, and at 8, 24 and 48 h post-injection. Synovial fluid samples were analysed for total nucleated cell count (TNCC), total protein (TP) and selected biomarkers (prostaglandin E2 [PGE2 ], interleukin-6 [IL-6], glycosaminoglycans [GAGs], type II collagen synthesis [CPII], matrix metalloproteinase [MMP]). Lameness was scored by visual examination and pressure plate analysis immediately prior to LPS injection, and at 8, 24 and 48 h post-injection. Clinical examinations were performed before treatment, immediately prior to LPS injection, at 2, 4 and 6 h post-injection, and then twice per day during the test period. RESULTS: Before treatment and intra-articular challenge, there were no statistically significant differences among the treatment groups for any of the parameters. After intra-articular challenge, the placebo group showed significantly higher synovial fluid TP, TNCC and PGE2 compared with the meloxicam group, although the model did not induce a relevant amount of lameness. Both nutraceuticals resulted in significantly lower synovial fluid TP, TNCC and PGE2 compared with placebo. No statistical differences in IL-6, GAGs, CPII or MMPs were observed among treatment groups. No adverse effects were observed. MAIN LIMITATIONS: Despite evidence of synovitis, lameness was too mild to detect. CONCLUSIONS: The preventive administration of these nutraceuticals showed anti-inflammatory effects in this validated synovitis model. Therefore, further studies of their clinical applicability are warranted. PMID- 27554765 TI - Texts for Talking: Evaluation of a Mobile Health Program Addressing Speech and Language Delay. AB - Speech and language delays are common developmental disorders that can lead to long-term academic and psychosocial impairments. Affected families often benefit from instruction in cultivating a language-rich home environment. This study investigated the feasibility of utilizing text messaging to deliver developmental education to families. Parents of children aged 11 to 36 months with concerning language development were enrolled in a 3-month text messaging program. Pre program and post-program telephone surveys were completed. All enrolled parents were of low socioeconomic status, and 48% were monolingual Spanish speakers. A total of 27 parents (87%) completed the program and follow-up survey. After program completion, parents reported increased awareness of language-promoting activities and local child development resources (P = .002; P = .005). Parents also reported increased engagement in language-promoting activities (P = .004). The marginal program cost was 37 cents per participant. Findings from this pilot study indicate that text messaging is a feasible, engaging, and inexpensive platform for delivering developmental education to families. PMID- 27554766 TI - Screening for Spinal Dysraphisms in Newborns With Sacral Dimples. AB - Sacral dimples are common physical examination findings among newborns and are rarely associated with spinal dysraphism. Screening ultrasonography for simple sacral dimples in the absence of other physical findings leads to unnecessary health care costs and undue stress on families. This study was a retrospective chart review of infants with a sacral dimple on examination who underwent spinal ultrasonography in the first week of life. The documented indication for ultrasonography was compared to standard guidelines. Among 151 infants in the study, 80% had a normal spinal ultrasound. Of infants with abnormal ultrasonography, 7 (5%) had abnormal spinal magnetic resonance imaging and 2 infants (1%) required neurosurgical intervention. Our study revealed that nearly one-third of infants who underwent spinal ultrasonography had a simple sacral dimple and low likelihood of spinal dysraphism according to existing guidelines. Among patients who underwent spinal ultrasonography in accordance with guidelines, only a small percentage required neurosurgical intervention indicating that guidelines may need to be revised. Larger studies involving multiple centers are necessary to assess this need. PMID- 27554767 TI - Severe Hypernatremia and Failure to Thrive. PMID- 27554763 TI - Inhibition of the Biosynthesis of Prostaglandin E2 By Low-Dose Aspirin: Implications for Adenocarcinoma Metastasis. AB - Meta-analyses have demonstrated that low-dose aspirin reduces the risk of developing adenocarcinoma metastasis, and when colon cancer is detected during aspirin treatment, there is a remarkable 83% reduction in risk of metastasis. As platelets participate in the metastatic process, the antiplatelet action of low dose aspirin likely contributes to its antimetastatic effect. Cycloxooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) also contributes to metastasis, and we addressed the hypothesis that low-dose aspirin also inhibits PGE2 biosynthesis. We show that low-dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers (P < 0.0001). Aspirin is found to be more potent in colon adenocarcinoma cells than in the platelet, and in lung adenocarcinoma cells, its inhibition is equivalent to that in the platelet. Inhibition of COX by aspirin in colon cancer cells is in the context of the metastasis of colon cancer primarily to the liver, the organ exposed to the same high concentrations of aspirin as the platelet. We find that the interaction of activated platelets with lung adenocarcinoma cells upregulates COX-2 expression and PGE2 biosynthesis, and inhibition of platelet COX-1 by aspirin inhibits PGE2 production by the platelet tumor cell aggregates. In conclusion, low-dose aspirin has a significant effect on extraplatelet cyclooxygenase and potently inhibits COX-2 in lung and colon adenocarcinoma cells. This supports a hypothesis that the remarkable prevention of metastasis from adenocarcinomas, and particularly from colon adenocarcinomas, by low-dose aspirin results from its effect on platelet COX-1 combined with inhibition of PGE2 biosynthesis in metastasizing tumor cells. Cancer Prev Res; 9(11); 855-65. (c)2016 AACR. PMID- 27554768 TI - Effect of ghrelin on regulation of splenic sympathetic nerve discharge. AB - Ghrelin influences immune system function and modulates the sympathetic nervous system; however, the contribution of ghrelin to neural-immune interactions is not well-established because the effect of ghrelin on splenic sympathetic nerve discharge (SND) is not known. This study tested the hypothesis that central ghrelin administration would inhibit splenic SND in anesthetized rats. Rats received intracerebroventricular (ICV) injections of ghrelin (1nmol/kg) or aCSF. Lumbar SND recordings provided a non-visceral nerve control. The ICV ghrelin administration significantly increased splenic and lumbar SND, whereas mean arterial pressure (MAP) was not altered. These findings provide fundamental information regarding the nature of sympathetic-immune interactions. PMID- 27554769 TI - Anxiety and physiological responses to the Trier Social Stress Test for Children in adolescents with cyclic vomiting syndrome. AB - This study compared anxiety and physiological responses during the Trier Social Stress Test for Children (TSST-C) in adolescents. 38 subjects (26 females) were enrolled: 11 cyclic vomiting syndrome (CVS), 11 anxiety, and 16 controls. Salivary cortisol, alpha-amylase and heart rate variability (HRV) were assessed during the TSST-C. Anxiety was measured by the Screen for Childhood Anxiety Related Emotional Disorders (SCARED), Anxiety Disorders Interview Schedule, and State-Trait Anxiety Inventory for Children (STAI-C). 11 anxiety and 7 CVS subjects had >=1 anxiety disorder. 82% in the anxiety and CVS groups met criteria for an anxiety disorder on the SCARED. Combining groups, cortisol increased from baseline to recovery during the TSST-C (p=0.0004) and the stressor to recovery (p=0.005). alpha-amylase did not differ during the TSST-C for the total sample, but increased for anxiety compared to controls from baseline to recovery (p=0.01). HRV decreased during the stressor (p=0.0001) and increased at recovery (p=0.004). No associations were found between biomarkers and trait anxiety. Associations were found between baseline HRV and pre-test state anxiety (r= 0.406, p=0.012) and between recovery HRV and post-test state anxiety (r=-0.501, p=0.002) for the total sample. Anxiety is prevalent in CVS warranting screening. HRV may serve as a biomarker for evaluating stress as a potential trigger for CVS episodes. State but not trait anxiety was associated with changes in HRV, suggesting acute anxiety may be more relevant in linking stress and CVS episodes. PMID- 27554770 TI - Changing paediatric emergency department model of care is associated with improvements in the National Emergency Access Target and a decrease in inpatient admissions. AB - OBJECTIVE: To assess the impact on patient flow as noted by the National Emergency Access Target (NEAT), with the introduction of a new Paediatric ED (PEM ED) model of care. METHODS: This longitudinal observational study was conducted at the Logan Hospital, a 344 bed public hospital in metropolitan Brisbane, which opened a physically separate, dedicated PEM ED on 14 October 2014, incorporating approximately 30% more staff, limited changes in processes and no changes in governance. De-identified data of the entire clientele from the ED Information System were compared 365 days before and after the opening of the PEM ED. RESULTS: Although the number of children presenting to ED increased by 23% (pre 18 142, post 22 391), the median length of stay decreased substantially from 152 min to 138 min, resulting in a 7.75% rise in presentations that met the NEAT target (pre 77.41%, post 85.16%; P < 0.0001). Admission to the ED Short Stay Unit rose by 16.48% (pre 5.38%, post 21.86%; P < 0.0001), whereas final disposition to the inpatient paediatric unit fell by 2.30% (pre 11.43, post 9.13%; P < 0.0001). The clinical presentations were similar pre and post across age, sex, ethnicity, referral and arrival mode, Australasian Triage Scale category, presenting problem and discharge diagnosis. CONCLUSION: NEAT times improved after changing the PEM ED model of care. Further studies may assist identifying which of the specific features within the new model are most effective for improving patient flow. PMID- 27554771 TI - Analysis of Genomewide DNA Methylation Reveals Differences in DNA Methylation Levels between Dormant and Naturally as well as Artificially Potentiated Pedicle Periosteum of Sika Deer (Cervus nippon). AB - Deer antlers are the only mammalian appendages that can fully regenerate each year from the permanent bony protuberances of the frontal bones, called pedicles. Pedicle periosteum (PP) is the key tissue for antler regeneration and the source of antler stem cells. The distal one third of the PP has acquired the ability to regenerate antlers and is termed the potentiated PP (PPP), whereas the proximal two thirds of the PP requires further interactions within its niche to launch antler regeneration and is termed the dormant PP (DPP). However, the molecular mechanisms underlying the process of potentiation from the DPP to the PPP are unknown. In this study, we used the fluorescence-labeled methylation-sensitive amplified polymorphism method to assess the levels of DNA methylation in both cells and tissues of the PPP and the DPP. The results showed that the levels of DNA methylation were significantly lower in the PPP compared to the DPP (P < 0.05). Therefore, DNA demethylation may be involved in the process of this potentiation. This involvement was further confirmed by functional testing by artificially creating a potentiated PP (aPPP) from DPP tissue. Moreover, we identified 15 methylated fragments by the methylation sensitive amplified polymorphism method that are either unique to the PPP or the DPP, which were further confirmed by Southern blot analysis. Taken together, our data suggest that DNA demethylation is involved in the process of PP potentiation, which is a prerequisite step for the initiation of antler regeneration. These findings provide the first experimental evidence to link epigenetic regulation and mammalian appendage regeneration. PMID- 27554772 TI - Disruption of calcitonin gene-related peptide signaling accelerates muscle denervation and dampens cytotoxic neuroinflammation in SOD1 mutant mice. AB - Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal vacuolization and glial activation are pathologic hallmarks in the superoxide dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide calcitonin gene-related peptide (CGRP) associated with vacuolization and astrogliosis in the spinal cord of these mice. We now show that CGRP abundance positively correlated with the severity of astrogliosis, but not vacuolization, in several motor and non-motor areas throughout the brain. SOD1 mice harboring a genetic depletion of the betaCGRP isoform showed reduced CGRP immunoreactivity associated with vacuolization, while motor functions, body weight, survival, and astrogliosis were not altered. When CGRP signaling was completely disrupted through genetic depletion of the CGRP receptor component, receptor activity modifying protein 1 (RAMP1), hind limb muscle denervation, and loss of muscle performance were accelerated, while body weight and survival were not affected. Dampened neuroinflammation, i.e., reduced levels of astrogliosis in the brain stem already in the pre-symptomatic disease stage, and reduced microgliosis and lymphocyte infiltrations during the late disease phase were additional neuropathology features in these mice. On the molecular level, mRNA expression levels of brain-derived neurotrophic factor (BDNF) and those of the anti inflammatory cytokine interleukin 6 (IL-6) were elevated, while those of several pro-inflammatory cytokines found reduced in the brain stem of RAMP1-deficient SOD1 mice at disease end stage. Our results thus identify an important, possibly dual role of CGRP in ALS pathogenesis. PMID- 27554774 TI - The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma. AB - BACKGROUND: Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker. METHODS: We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV). RESULTS: Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors. CONCLUSION: Large BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning. PMID- 27554773 TI - Toxin bioportides: exploring toxin biological activity and multifunctionality. AB - Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides-a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity. PMID- 27554775 TI - Monascin from Monascus-Fermented Products Reduces Oxidative Stress and Amyloid beta Toxicity via DAF-16/FOXO in Caenorhabditis elegans. AB - Amyloid-beta (Abeta)-induced oxidative stress and toxicity are leading risk factors for Alzheimer's disease (AD). Monascin (MS) is a novel compound proposed for antioxidative stress applications and is derived from an edible fungus secondary metabolite. This study assessed the effects of MS on oxidative stress, paralysis, Abeta accumulation, and lifespan in the nematode Caenorhabditis elegans and investigated its underlying mechanisms of action. The results showed that MS increased the survival of C. elegans under juglone-induced oxidative stress and attenuated endogenous levels of reactive oxygen species. Furthermore, MS induced a decline in Abeta-induced paralysis phenotype and Abeta deposits in the transgenic strains CL4176 and CL2006 of C. elegans, which expresses human muscle-specific Abeta1-42 in the cytoplasm of body wall muscle cells. In addition, mRNA levels of strain CL4176 of several antioxidant genes (sod-1, sod 2, sod-3, hsp16.2) and daf-16 were up-regulated by MS treatment when compared to the nontreated controls. Further evidence showed that MS treatment in C. elegans strains lacking DAF-16/FOXO did not affect paralysis or lifespan phenotypes. The findings indicate that MS reduces oxidative stress and Abeta toxicity via DAF-16 in C. elegans, suggesting that MS can be used for the prevention of AD-associated oxidative stress complications. PMID- 27554776 TI - Lymph Node Fine-Needle Cytology of Non-Hodgkin Lymphoma: Diagnosis and Classification by Flow Cytometry. AB - In the last decades, lymph node fine-needle cytology (FNC), coupled with flow cytometry (FC), has gained a role in the diagnosis and classification of non Hodgkin lymphoma (NHL). The combination of FNC/FC allows the diagnosis and classification of NHL in lymph node samples with a high sensitivity and specificity by combining cytological features and specific phenotypic profiles. The present review provides a brief technical description of FC and a detailed analysis of the current markers and their combinations (diagnostic algorithm) for the diagnosis and classification of NHL. The basic principles of clonality assessment, as well as the diagnostic strengths and weaknesses of the procedure, are reported. The current diagnostic algorithms for NHL classification are critically reviewed with a focus on specific problems related to single entities. Moreover, this review provides a detailed analysis of the different clinical contexts in which FNC/FC is performed and related implications. Future and further applications of FNC/FC for NHL are also discussed. PMID- 27554777 TI - Cyclic Oligosaccharide-Based Chiral Stationary Phases Applicable to Drug Purity Control; A Review. AB - Oligosaccharide-based chiral stationary phases are frequently used for enantioselective separations by different chromatographic techniques, namely gas chromatography, high performance liquid chromatography, supercritical fluid chromatography or capillary electrochromatography. Their multimodal application potential (they are compatible with both polar and/or non-polar mobile phases) makes them suitable chiral selector candidates for separation of a wide variety of structurally diverse compounds. In this paper, separation systems utilizing cyclodextrin- or cyclofructan-based chiral stationary phases in analyses of pharmacologically active compounds are summarized. The review covers the period from 2000 to 2015. This review article can be helpful to analysts searching for an appropriate method for the separation/determination of pharmaceuticals of their interest. PMID- 27554778 TI - Effect of Hypoglycemia on the Incidence of Revision in Total Knee Arthroplasty. AB - BACKGROUND: It is well established that diabetic patients undergoing total knee arthroplasty (TKA) are more susceptible to infection, problematic wound healing, and overall higher complication rates. However, a paucity in current literature exists. The purpose of this study was to determine the effect of hypoglycemia on TKA revision (rTKA) incidence by analyzing a national private payer database for procedures performed between 2007 and 2015 Q1 Q2. METHODS: A retrospective review of a national private payer database within the PearlDiver Supercomputer application for patients undergoing TKA with blood glucose levels from 20 to 219 mg/mL, in 10-mg/mL increments, was conducted. Patients who underwent TKA were identified by Current Procedural Terminology (CPT) and International Classification of Disease (ICD) codes. Glucose ranges were identified by filtering for Logical Observation Identifiers Names and Codes within the PearlDiver database. Patients with diagnosed diabetes mellitus type I or II were excluded by using ICD-9 codes 250.00-250.03, 250.10-250.13, and 250.20-250.21. rTKA causes including mechanical loosening, failure/break, periprosthetic fracture, osteolysis, infection, pain, arthrofibrosis, instability, and trauma were identified with CPT and ICD-9 codes. Statistical analysis was primarily descriptive. RESULTS: Our query returned 264,824 TKAs, of which 12,852 (4.9%) were revised. Most TKAs were performed with a glucose of 70-99 mg/mL (26.1%), followed by 100-109 mg/mL (18.5%). Patients with TKAs performed with glucose 20 29 mg/mL had the highest rate of revision (17.2%; P < .001). Infection was the most common cause of revision among all glucose ranges (P < .001). CONCLUSION: Infection remains one of the most common causes of rTKA irrespective of glucose level. Our results suggest that hypoglycemia may increase revision rates among TKA patients. Tight glycemic control before and during surgery may be warranted. PMID- 27554779 TI - Characterizing the Acute Phase Response in Healthy Patients Following Total Joint Arthroplasty: Predictable and Consistent. AB - BACKGROUND: During surgery, trauma to musculoskeletal tissue induces a systemic reaction known as the acute phase response (APR). When excessive or prolonged, the APR has been implicated as an underlying cause of surgical complications. The purpose of this study was to determine the typical APR following total joint arthroplasty in a healthy population defined by the Charlson Comorbidity Index (CCI). METHODS: This retrospective study identified 180 healthy patients (CCI < 2) who underwent total joint arthroplasty by a single surgeon for primary osteoarthritis from 2013 to 2015. Serial measurements of C-reactive protein (CRP) and fibrinogen were obtained preoperative, perioperative, and at 2 and 6 weeks postoperative. RESULTS: Postoperative CRP peaked during the inpatient period and returned to baseline by 2 weeks. Fibrinogen peaked after CRP and returned to baseline by 6 weeks. Elevated preoperative CRP correlated with a more robust postoperative APR for both total hip arthroplasty and total knee arthroplasty, suggesting that a patient's preoperative inflammatory state correlates with the magnitude of the postoperative APR. CONCLUSION: Measurement of preoperative acute phase reactants may provide an objective means to predict a patient's risk of postoperative dysregulation of the APR and complications. PMID- 27554780 TI - The Utility of Postoperative Radiographs 2 Years After Primary Total Knee Arthroplasty. AB - BACKGROUND: Radiographs are routinely used to evaluate patients postoperatively after total knee arthroplasty, but no evidence-based guidelines exist regarding their use. The purpose of this study is to quantify the use of radiographs within 2 years of primary total knee arthroplasty by one surgeon and to determine if routine studies in asymptomatic patients altered patient management. METHODS: Patients undergoing consecutive primary total knee arthroplasties between 2008 and 2010 were identified. Patients undergoing revision or additional simultaneous procedures or those with less than 6 months of radiographic follow-up were excluded. Operative and clinic notes, radiographs, and radiology reports were reviewed. RESULTS: A total of 263 patients were identified; each patient had an average of 13.5 +/- 3.8 individual radiographs obtained in 6.5 +/- 1.7 series. Twelve radiographic series were noted to have abnormal findings by either the attending surgeon or by radiology report. Three of these patients underwent reoperation directly related to the findings; 2 for deep infections and 1 for extensor mechanism disruption. All 3 patients had reported abnormal symptoms when their films were obtained. The remaining 9 abnormal radiographic findings included focal lucencies or osteolysis, asymmetric spacer wear, a healing stress fracture, an inferior patellar avulsion fracture, and heterotopic ossification. No patient had symptoms attributable to these findings when the radiographs were obtained, and in no case was the management altered based on these finding. CONCLUSION: This study suggests that the observed frequency of routine postoperative radiographs in asymptomatic patients may not be necessary in the first 2 years after primary total knee arthroplasty. PMID- 27554781 TI - No Effect of a Bipolar Sealer on Total Blood Loss or Blood Transfusion in Nonseptic Revision Knee Arthroplasty-A Prospective Study With Matched Retrospective Controls. AB - BACKGROUND: Postoperative anemia is frequent after revision of total knee arthroplasty (TKA) with reported transfusion rates up to 83%. Despite increased efforts of reducing blood loss and enhancing fast recovery within the fast-track setup, a considerable transfusion rate is still evident. The aim of this study was therefore to evaluate the effect of a bipolar sealer on blood loss and transfusion in revision TKA. METHODS: In this single-center prospective cohort study with retrospective controls, 51 patients were enrolled in a fast-track setup for revision TKA without the use of a tourniquet. Twenty-five prospectively enrolled patients received treatment with both a bipolar sealer and electrocautery, whereas 26 patients had received treatment with a conventional electrocautery only in the retrospective group. RESULTS: No significant differences were found neither for calculated blood loss, with 1397 (standard deviation, +/- 452) mL in the bipolar sealer group vs 1452 (SD, +/- 530) mL in the control group (P = .66), nor for blood transfusion rates of 53% and 46% (P = .89), respectively. Four controls were readmitted within 90 days follow-up. CONCLUSION: The use of a bipolar sealer in a TKA revision setting without the use of a tourniquet did not reduce blood loss or blood transfusion rates. PMID- 27554782 TI - Rate of Transfusions After Total Knee Arthroplasty in Patients Receiving Lovenox or High-Dose Aspirin. AB - BACKGROUND: Controversy continues regarding the use of powerful anticoagulants for venous thromboembolism prophylaxis in patients undergoing total knee arthroplasty (TKA). To comply with institution-mandated guidelines and pressure from hospitalist intent on complying with conventionally recommended anticoagulation guidelines, we singularly changed our chemoprophylaxis practice from using aspirin to Lovenox and noted that transfusion rates increased substantially. METHODS: A retrospective case review was performed to evaluate transfusion requirement differences in primary TKA patients receiving Lovenox (unilateral TKA: n = 135, bilateral TKA: n = 44) or aspirin (unilateral TKA: n = 153, bilateral TKA: n = 45) for venous thromboembolism prophylaxis. Pearson's chi square tests were used to evaluate surgical complications and the rate of transfusions between aspirin and Lovenox groups. Independent t tests were used to evaluate the units of packed red blood cells transfused, hemoglobin drop, and hematocrit drop between aspirin and Lovenox groups. RESULTS: Lovenox was found to significantly increase (P < .01) the rate of transfusion, units of packed red blood cells, hemoglobin drop, and hematocrit drop compared to aspirin in both unilateral and bilateral TKA patients, without significantly decreasing venous thromboembolism events (aspirin: 3 pulmonary embolisms and 4 deep venous thrombosis; Lovenox: 3 pulmonary embolisms and 2 deep venous thrombosis). CONCLUSION: Our findings suggest that aspirin is as effective as Lovenox in preventing venous thromboembolism and that the use of Lovenox significantly increases the likelihood of requiring transfusions after surgery. PMID- 27554783 TI - Comparable Stability of Cemented vs Press-Fit Placed Stems in Revision Total Knee Arthroplasty With Mild to Moderate Bone Loss: 6.5-Year Results From a Randomized Controlled Trial With Radiostereometric Analysis. AB - BACKGROUND: Short-term stability after revision total knee arthroplasty (TKA) with either fully cemented or hybrid-placed implants is comparable. Interestingly, implant micromotion >1 mm/degree occurred with both techniques which might increase the risk of loosening in the midterm or long-term. Therefore, the present study investigated midterm stability and clinical results of fully cemented vs hybrid-placed revision TKA, with mild to moderate bone loss, using radiostereometric analysis (RSA). METHODS: This study involves the prolonged follow-up of a previous randomized controlled trial. RSA images taken at baseline, 6 weeks, 3 and 6 months, and 1, 2 and 6.5 years of follow-up were analyzed. Stability of the femoral and tibial implants was evaluated using total translation and rotation, based on the micromotion determined with model-based RSA. RESULTS: Of the 30 patients who completed the 2-year follow-up in the original randomized controlled trial, 23 (12 cement, 11 hybrid) were available for follow-up at 6.5-year (range 5.4-7.3). There were no differences in median total translation and rotation of the femoral and tibial components between the 2 groups, and none of the clinical scores differed between the groups. Interestingly, in the group with cemented stems, 5 tibia implants showed >1 mm/degree micromotion compared to none in the hybrid group. CONCLUSION: There was no difference in median micromotion and clinical outcome between fully cemented and hybrid-placed revision TKA 6.5 years postoperatively. Two femur components showed progressive migration over time whereas tibia components migrate especially in the first year followed by a stable situation. Whether this will lead to loosening and re-revisions remains to be investigated. PMID- 27554784 TI - Comparison of Bone Remodeling Between an Anatomic Short Stem and a Straight Stem in 1-Stage Bilateral Total Hip Arthroplasty. AB - BACKGROUND: Femurs of dysplastic hips exhibit specific abnormalities, and use of modular or specially designed components is recommended. An anatomic short stem was previously designed specifically for dysplastic hips using 3-dimensional data acquired from dysplastic patients. To investigate effects of stem geometry on bone remodeling, we undertook a prospective, randomized study of patients who had undergone 1-stage bilateral total hip arthroplasty (THA) with the anatomic short stem on one side and a conventional straight stem on the other. METHODS: The study included 36 patients who underwent the above THA procedure. We assessed bone mineral density as well as the presence of cancellous condensation or bony atrophy due to stress shielding based on the analysis of Gruen's zones and newly defined equal-interval zones, at an average follow-up period of 9.2 years. RESULTS: All stems were bone ingrown stable. Cancellous condensation was observed more proximally, and areas of bone atrophy were narrower on the anatomic short stem side than on the straight stem side. Bone mineral density values reflected results of cancellous condensation and stress shielding and were higher in more proximal zones on the anatomic short stem side than on the straight stem side. CONCLUSION: Although radiographic results indicated good midterm outcomes of THA with both stems, the loading pattern differed. The anatomic short stem achieved its design purpose in terms of proximal fixation and load transfer and led to better preservation of the proximal femur. PMID- 27554785 TI - Corrigendum to 'Difference in Stem Alignment Between the Direct Anterior Approach and the Posterolateral Approach in Total Hip Arthroplasty'. [The Journal of Arthroplasty 30/10 (2015) 1761-1766]. PMID- 27554786 TI - Leaf venation, as a resistor, to optimize a switchable IR absorber. AB - Leaf vascular patterns are the mechanisms and mechanical support for the transportation of fluidics for photosynthesis and leaf development properties. Vascular hierarchical networks in leaves have far-reaching functions in optimal transport efficiency of functional fluidics. Embedding leaf morphogenesis as a resistor network is significant in the optimization of a translucent thermally functional material. This will enable regulation through pressure equalization by diminishing flow pressure variation. This paper investigates nature's vasculature networks that exhibit hierarchical branching scaling applied to microfluidics. To enable optimum potential for pressure drop regulation by algorithm design. This code analysis of circuit conduit optimization for transport fluidic flow resistance is validated against CFD simulation, within a closed loop network. The paper will propose this self-optimization, characterization by resistance seeking targeting to determine a microfluidic network as a resistor. To advance a thermally function material as a switchable IR absorber. PMID- 27554787 TI - Atrazine activates multiple signaling pathways enhancing the rapid hCG-induced androgenesis in rat Leydig cells. AB - Atrazine (ATR) is an endocrine disruptor that affects steroidogenic process, resulting in disruption of reproductive function of the male and female gonads. In this study, we used the primary culture of peripubertal Leydig cells to investigate the effect of ATR on the rapid androgen production stimulated by human chorionic gonadotropin (hCG). We demonstrated that ATR activated multiple signaling pathways enhancing the rapid hCG-stimulated androgen biosynthesis in Leydig cells. Low hCG concentration (0.25ng/mL) caused cAMP-independent, but ERK1/2-dependent increase in androgen production after 60min of incubation. Co treatment with ATR for 60min enhanced the cAMP production in hCG-stimulated cells. Accumulation of androgens was prevented by addition of U0126, N-acetyl-l cysteine and AG1478. Co-treatment with hCG and ATR for 60min did not alter steroidogenic acute regulatory protein (Star) mRNA level in Leydig cells. After 120min, hCG further increased androgenesis in Leydig cells that was sensitive to inhibition of the cAMP/PKA, ERK1/2 and ROS signaling pathways. Co-treatment with ATR for 120min further enhanced the hCG-induced androgen production, which was prevented by inhibition of the calcium, PKC and EGFR signaling cascades. After 120min, ATR enhanced the expression of Star mRNA in hCG-stimulated Leydig cells through activation of the PKA and PKC pathway. Collectively, these data suggest that exposure to ATR caused perturbations in multiple signaling pathways, thus enhancing the rapid hCG-dependent androgen biosynthesis in peripubertal Leydig cells. PMID- 27554788 TI - Game of Trans-Kingdom Effectors. AB - TplE, a type VI secreted (phospho)lipase, has been identified as the third trans kingdom effector of Pseudomonas aeruginosa, targeting both prokaryotic and eukaryotic hosts. Indeed, TplE triggers the killing of bacterial competitors and promotes autophagy in epithelial cells once localized to the endoplasmic reticulum. PMID- 27554789 TI - Costs of formal and informal care at home for people with dementia: 'Expert panel' opinions from staff and informal carers. AB - Effective home support in dementia is key in delaying nursing home admission. However, home support is frequently not tailored to the individual needs of people with dementia. Staff allocating home support services may not identify important care needs, which only be recognised by informal carers. The purpose of this study was to explore the balance of informal and formal home support and their associated costs from the perspectives of both informal carers and paid staff. Five case vignettes of people with dementia were designed based on an existing English data set from a European study into transition into long-term care (the RightTimePlaceCare programme), representing 42 per cent of the English sample. In total, 14 informal carers and 14 paid staff were consulted in separate groups, as expert panels, regarding their recommendations for home care services for each vignette. Care recommendations of carers and staff were costed based on nationally available unit costs and compared. Informal carers allocated fewer hours of care than staff. Personal and domestic home care and day care centres were the most frequently recommended formal services by both groups, and some vignettes of people with dementia were recommended for care home admission. The ratio of costs of informal versus formal support was relatively equal for paid staff, yet unbalanced from the perspectives of informal carers with a greater proportion of formal care costs. Recommendations from this study can help shape dementia care to be more tailored to the individual needs of people with dementia and their carers. PMID- 27554790 TI - Stability of the cargo regions of the cfr-carrying, multiresistance plasmid pSP01 from Staphylococcus epidermidis. AB - This study investigated the stability or instability - i.e. the ability or inability to undergo excision in circular form - of the four cargo regions (cr1 to cr4) of the novel cfr-carrying, multiresistance plasmid pSP01, arboured by a clinical Staphylococcus epidermidis isolate. Only cr4 proved unstable. The stability of cr1 and cr2 was substantially expected. Insertion sequences (ISs) played an important role in the stability of cr3 (the cfr gene context) and in the instability of cr4. Whereas the stability of cfr genetic contexts is associated with the presence of a single IS copy (istAS-istBS in cr3), their instability is associated with two identical, flanking ISs with the same orientation. cr4 is bracketed between two identical IS257 elements, and appears to behave as a composite transposon. Its instability is of interest because of the existence of a closely related cfr plasmid from S. epidermidis (pSP01.1) that differs from pSP01 only by the lack of cr4. An integration/recombination mechanism is suggested to explain how cr4 may have moved to pSP01.1 to form pSP01. PMID- 27554791 TI - Immune signature of urothelial cancer associated with grade, recurrence, and invasion. AB - BACKGROUND: Urothelial carcinoma (UC) is one of most common genitourinary malignancy and the spectrum of disease ranges from in situ lesions to muscle invasive cancers. The non-muscle-invasive lesions have tendency to recur or progress to muscle-invasive disease. The study of the immune profile may identify immune determinants associated with high-grade, recurrence, and invasion in patients with UC. METHODS: Pathway-focused RT(2) profiler arrays were used to screen patients with UC for dysregulation of candidate genes of Th1-Th2-Th3 and NFkappaB pathways, which were then validated by real-time polymerase chain reaction on tumor samples and correlated with grade, recurrence, and invasion of tumors to identify their role in predicting behavior of the tumor. The cytokines found associated with recurrence were then validated in urine of patients with UC. RESULTS: IFNgamma, IL2, IL4, IL10, IL17, CCL7, CTLA4, and SPP1 of the cytokine pathway and TLR4, TLR3, RELA, NFkappaB1, and MYD88 of the NFkappaB pathway were found differentially expressed in patients with urothelial cancer by array and quantative real-time polymerase chain reaction. Among these, IL10 and SPP1 were found consistently up-regulated in high-grade, invasive, and recurrent cases and up-regulated IL10 and CTLA4 were found associated with a short recurrence-free survival time (P = 0.001 and P = 0.065). Urinary IL10 concentration was significantly higher in both patients with cancer and cystitis compared with healthy controls, but the difference in concentration between patients with cancer and cystitis patients was not statistically significant. However, urinary CTLA4 concentrations were found to be significantly higher in urothelial cancer patients compared with healthy controls and cystitis cases and found to be associated with poor recurrence-free survival. CONCLUSION: The study indicates that high urinary CTLA4 concentration raises the index of suspicion of recurrence in a known case of urothelial cancer and may be used as a surveillance marker. PMID- 27554792 TI - Hydrogel microphones for stealthy underwater listening. AB - Exploring the abundant resources in the ocean requires underwater acoustic detectors with a high-sensitivity reception of low-frequency sound from greater distances and zero reflections. Here we address both challenges by integrating an easily deformable network of metal nanoparticles in a hydrogel matrix for use as a cavity-free microphone. Since metal nanoparticles can be densely implanted as inclusions, and can even be arranged in coherent arrays, this microphone can detect static loads and air breezes from different angles, as well as underwater acoustic signals from 20 Hz to 3 kHz at amplitudes as low as 4 Pa. Unlike dielectric capacitors or cavity-based microphones that respond to stimuli by deforming the device in thickness directions, this hydrogel device responds with a transient modulation of electric double layers, resulting in an extraordinary sensitivity (217 nF kPa(-1) or 24 MUC N(-1) at a bias of 1.0 V) without using any signal amplification tools. PMID- 27554794 TI - Exploring risk factors associated with intimate partner violence in Vietnam: results from a cross-sectional national survey. AB - OBJECTIVES: Empirical evidence documents that some risk factors for intimate partner violence (IPV) are similar across contexts, while others differ considerably. In Vietnam, there was a need to investigate risk factors for IPV to support evidence-based policy and programming. METHODS: Using the dataset gathered in the 2010 National Study on Domestic Violence against Women, forty variables were explored in logistic regression analysis, including socio demographic characteristics of women and their husbands, other experiences with violence, husband's behaviours, family support, and context-specific variables such as the sex of their children. RESULTS: Fifteen independent factors remained strongly associated with IPV. Significant risk was associated with husbands' behaviour that supports male power (extra-marital relationships; fighting with other men) and alcohol use. Violence experienced in childhood increased the likelihood of women experiencing and of men perpetrating IPV. Notable was further the association with women's higher financial contribution to the household and lack of association with not having sons. CONCLUSIONS: The findings support theories describing how underlying gender and power imbalance are fundamental causes of IPV and indicate the need for context-specific interventions. PMID- 27554795 TI - Luminescent Europium(III) Coordination Zippers Linked with Thiophene-Based Bridges. AB - Novel Eu(III) coordination polymers [Eu(hfa)3 (dpt)]n (dpt: 2,5 bis(diphenylphosphoryl)thiophene) and [Eu(hfa)3 (dpedot)]n (dpedot: 2,5 bis(diphenylphosphoryl)ethylenedioxythiophene) with hydrogen-bonded zipper structures are reported. The coordination polymers are composed of Eu(III) ions, hexafluoroacetylacetonato ligands, and thiophene-based phosphine oxide bridges. The zig-zag orientation of single polymer chains induced the formation of densely packed coordination structures with multiple intermolecular interactions, resulting in thermal stability above 300 degrees C. They exhibit a high intrinsic emission quantum yield (ca. 80 %) due to their asymmetrical and low vibrational coordination structures around Eu(III) ions. Furthermore, the characteristic alternative orientation of substituents also contributes to the dramatically high ligand-to-metal energy transfer efficiencies of up to 80 % in the solid state. PMID- 27554793 TI - Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings. AB - Epilepsy is among the most common brain network disorders, and it is associated with substantial morbidity and increased mortality. Although focal epilepsy was traditionally considered a regional brain disorder, growing evidence has demonstrated widespread network alterations in this disorder that extend beyond the epileptogenic zone from which seizures originate. The goal of this review is to summarize recent investigations examining functional and structural connectivity alterations in focal epilepsy, including neuroimaging and electrophysiologic studies utilizing model-based or data-driven analytic methods. A significant subset of studies in both mesial temporal lobe epilepsy and focal neocortical epilepsy have demonstrated patterns of increased connectivity related to the epileptogenic zone, coupled with decreased connectivity in widespread distal networks. Connectivity patterns appear to be related to the duration and severity of disease, suggesting progressive connectivity reorganization in the setting of recurrent seizures over time. Global resting-state connectivity disturbances in focal epilepsy have been linked to neurocognitive problems, including memory and language disturbances. Although it is possible that increased connectivity in a particular brain region may enhance the propensity for seizure generation, it is not clear if global reductions in connectivity represent the damaging consequences of recurrent seizures, or an adaptive mechanism to prevent seizure propagation away from the epileptogenic zone. Overall, studying the connectome in focal epilepsy is a critical endeavor that may lead to improved strategies for epileptogenic-zone localization, surgical outcome prediction, and a better understanding of the neuropsychological implications of recurrent seizures. PMID- 27554796 TI - Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes. AB - OBJECTIVES: Accumulating evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes, making BMSCs a promising source of cardiomyocytes for transplantation. However, little is known about the molecular mechanisms underlying myogenic conversion of BMSCs. METHODS: This study was designed to investigate the functional role of caveolin-1 in the cardiomyocyte differentiation of BMSCs and to explore the potential underlying molecular mechanisms. RESULTS: BMSC differentiation was induced by treatment with 10 MUM 5-azacytidine, and immunofluorescence assay showed that the expression of cardiomyocyte marker cardiac troponin T (cTnT) was significantly increased compared with a control group. Meanwhile, an increased caveolin-1 expression was found during the 5-azacytidine-induced BMSC differentiation. Additionally, the role of caveolin-1 in the differentiation process was then studied by using caveolin-1 siRNAs. We found that silencing caveolin-1 during induction remarkably enhanced the expression of cardiomyocyte marker genes, including cTnT, Nkx2.5 (cardiac-specific transcription factor), alpha-cardiac actin and alpha-myosin heavy chain (alpha-MHC). Moreover, we observed that downregulation of caveolin-1 was accompanied by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. CONCLUSIONS: Taken together, these findings demonstrate that caveolin-1 plays an important role in the differentiation of BMSCs into cardiomyocytes in conjunction with the STAT3 pathway. PMID- 27554798 TI - Incidence, characteristics and survival outcomes of out-of-hospital cardiac arrest in children and adolescents between 1997 and 2014 in Perth, Western Australia. AB - OBJECTIVE: The present study was to describe the trends in the incidence, characteristics and survival of paediatric out-of-hospital cardiac arrest (OHCA) over an 18 year period. METHODS: We conducted a population-based retrospective cohort study using prospectively collected data from all OHCA patients aged <18 years who were attended by St John Ambulance Western Australia paramedics in the Perth metropolitan area, WA, between 1997 and 2014. The incidence, characteristics and survival were compared across 4 year periods (1997-2000, 2001 2005, 2006-2010 and 2011-2014). The Paediatric Cerebral Performance Category at hospital discharge was determined by medical record review. Incidence per 100 000 population was calculated for four age groups (<1, 1-4, 5-12 and 13-17). RESULTS: In total, 723 OHCAs were identified, and 451 (62.4%) had resuscitation commenced by paramedics. The patients were predominantly male (61.6%) with a median age of 2 years (IQR 0-14 years). Bystander CPR increased over time from 35.0% (1997 2000) to 63.0% (2011-2014) (P < 0.001). Any return of spontaneous circulation was 39/451 (8.6%), and survival to hospital discharge was 21/451 (5.0%). Of the 20 survivors assessed, 11 had good neurological status at hospital discharge (Paediatric Cerebral Performance Category 1 or 2). The overall incidence decreased from 14.1 (1997-2000) to 8.7 (2011-2014) per 100 000 population (P < 0.001). This was almost halved in children aged <1 year group (P < 0.001). CONCLUSION: The incidence of paediatric OHCA decreased over time, but survival remained poor. Strategies to strengthen the chain of survival for paediatric OHCA need to be considered. PMID- 27554797 TI - Microbiota as a mediator of cancer progression and therapy. AB - Complex and intricate circuitries regulate cellular proliferation, survival, and growth, and alterations of this network through genetic and epigenetic events result in aberrant cellular behaviors, often leading to carcinogenesis. Although specific germline mutations have been recognized as cancer inducers, the vast majority of neoplastic changes in humans occur through environmental exposure, lifestyle, and diet. An emerging concept in cancer biology implicates the microbiota as a powerful environmental factor modulating the carcinogenic process. For example, the intestinal microbiota influences cancer development or therapeutic responses through specific activities (immune responses, metabolites, microbial structures, and toxins). The numerous effects of microbiota on carcinogenesis, ranging from promoting, preventing, or even influencing therapeutic outcomes, highlight the complex relationship between the biota and the host. In this review, we discuss the latest findings on this complex microbial interaction with the host and highlight potential mechanisms by which the microbiota mediates such a wide impact on carcinogenesis. PMID- 27554799 TI - Patents: problem or panacea? PMID- 27554800 TI - Maximum limit to the number of myosin II motors participating in processive sliding of actin. AB - In this work, we analysed processive sliding and breakage of actin filaments at various heavy meromyosin (HMM) densities and ATP concentrations in IVMA. We observed that with addition of ATP solution, the actin filaments fragmented stochastically; we then determined mean length and velocity of surviving actin filaments post breakage. Average filament length decreased with increase in HMM density at constant ATP, and increased with increase in ATP concentration at constant HMM density. Using density of HMM molecules and length of actin, we estimated the number of HMM molecules per actin filament (N) that participate in processive sliding of actin. N is solely a function of ATP concentration: 88 +/- 24 and 54 +/- 22 HMM molecules (mean +/- S.D.) at 2 mM and 0.1 mM ATP respectively. Processive sliding of actin filament was observed only when N lay within a minimum lower limit (Nmin) and a maximum upper limit (Nmax) to the number of HMM molecules. When N < Nmin the actin filament diffused away from the surface and processivity was lost and when N > Nmax the filament underwent breakage eventually and could not sustain processive sliding. We postulate this maximum upper limit arises due to increased number of strongly bound myosin heads. PMID- 27554802 TI - Targeting the endocannabinoid system: future therapeutic strategies. AB - The endocannabinoid system (ECS) is involved in many physiological regulation pathways in the human body, which makes this system the target of many drugs and therapies. In this review, we highlight the latest studies regarding the role of the ECS and the drugs that target it, with a particular focus on the basis for the discovery of new cannabinoid-based drugs. In addition, we propose some key steps, such as the creation of a cannabinoid-receptor interaction matrix (CRIM) and the use of metabolomics, toward the development of improved and more specific drugs for each relevant disease. PMID- 27554801 TI - Macrophage polarization in response to epigenetic modifiers during infection and inflammation. AB - Macrophages are a heterogeneous population of phagocytic cells present in all tissues. Recently, several drugs that target the epigenetic machinery have emerged as attractive molecules for treating infection and inflammation by modulating macrophages. Treatment of lipopolysaccharide (LPS)-challenged macrophages with epigenetic modifiers leads to phenotype switching. This could provide stimulatory/destructive (M1) or suppressive/protective (M2) therapeutic strategies, which are crucial in the cytokine milieu in which the macrophages reside. In this review, we provide an overview of macrophage functional diversity during various diseases, including infection, as well as the current status in the development and clinical utility of epigenetic modifiers. PMID- 27554804 TI - Recipients Inherit a Cardiovascular Risk Factor From Bone Marrow Donors: Implications for Screening of Donors? PMID- 27554803 TI - Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard dose ticagrelor in healthy subjects: an open-label randomized controlled trial. AB - Ticagrelor has a greater antiplatelet efficacy than clopidogrel but may be accompanied by an increased risk of bleeding. This study evaluated the antiplatelet effect and pharmacokinetic profile of low-dose ticagrelor in healthy Chinese volunteers. Thirty healthy subjects were randomized to receive standard dose ticagrelor (180-mg loading dose, 90-mg twice daily [bid] [n = 10]), low-dose ticagrelor (90-mg loading dose, 45-mg bid [n = 10]), or clopidogrel (600-mg loading dose, 75-mg once daily [n = 10]). Platelet reactivity was assessed by using the VerifyNow P2Y12 assay at baseline and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours post-dosing. The ticagrelor and AR-C124910XX concentrations were measured for pharmacokinetic analysis. The percentage inhibition of P2Y12 reaction units was higher in the low-dose and standard-dose ticagrelor group than in the clopidogrel group at 0.5, 1, 2, 4, 8, and 48 hours post-dosing (P < 0.05 for all), but did not differ significantly between the two ticagrelor doses at any time-point (P > 0.05). The plasma ticagrelor and ARC124910XX concentrations were approximately 2-fold higher with standard-dose versus low-dose ticagrelor. No serious adverse events were reported. In conclusion, low-dose ticagrelor achieved faster and higher inhibition of platelet functions in healthy Chinese subjects than did clopidogrel, with an antiplatelet efficacy similar to that of standard dose ticagrelor. PMID- 27554805 TI - Therapeutic Strategies for Alzheimer's and Parkinson's Diseases by Means of Drug Delivery Systems. AB - Alzheimer's and Parkinson's diseases are prevalent neurodegenerative disorders worldwide, which are essentially related to aging. Within the remarkable era of nanomedicine, nowadays several delivery systems have been suggested to improve the treatment of these disorders, namely, liposomes, micelles, nanoparticles (polymeric, lipid, metallic and inorganic), exosomes, dendrimers and fullerenes. The advantage that has been claimed to these delivery systems is that they facilitate the passage of drugs through the blood brain barrier (BBB), enabling targeting before body degradation, and increasing therapeutic efficacy, comparied to conventional pharmaceutical dosage forms. This review article provides a state of the art regarding the drug delivery systems that have been studied for the treatment of Alzheimer's and Parkinson's diseases. It begins with a brief description of the central nervous system (CNS) and the mechanisms involved in the development of these diseases. Later, some examples of drugs used in the treatment of these neurodegenerative diseases are presented, which are currently available in conventional pharmaceutical dosage forms, and in new drug delivery systems that are under development. PMID- 27554806 TI - Hyaluronan in Medical Practice. AB - Hyaluronan is the major extracellular matrix glycosaminoglycan polymer present in vertebrate tissues, with a molar mass that can reach several megaDaltons. It is particularly prominent in the matrix of tissues undergoing rapid turnover, in fetal tissues, and wherever regeneration and repair are occurring. Hyaluronan has highly varied biological functions often dependent on molar mass, however they are highly dependent on source of hyaluronan, its purity and nature of contaminants. Hyaluronan of highmolar- mass is known for its anti-angiogenic, anti-inflammatory and immunosuppressive properties, unlike hyaluronan of low molar-mass that has the opposite effects. Hyaluronan also has a broad range of clinical applications, such as intra-articular injection, in ophthalmology, otolaryngology, wound healing, and commercially in the cosmetic industry, as well as in drug delivery systems. Currently, polymers of hyaluronan are modified in order to improve their properties, including bioavailability and resistance to degradation. Because of greatly increased interest currently in hyaluronan, the multiple functions of the polymer are presented here, including medicine and industry, as well as recent progress in the formulation of hyaluronan-based materials. PMID- 27554807 TI - Vanadium, Ruthenium and Copper Compounds: A New Class of Nonplatinum Metallodrugs with Anticancer Activity. AB - Cancer is a group of diseases involving abnormal cell growth. The cells grow uncontrollably with the potential to invade and spread to other parts of the body. This disease is one of the principal death causes in the world, thus becoming a significant topic of scientific research. On the other hand, transition metals play a fundamental role in different living systems. In particular, Metallodrugs represent new and powerful tools for diverse therapeutic applications. To date, various metallodrugs display interesting biological activities for chemotherapy. In this field, cisplatin was the first inorganic compound with high relevance in cancer treatment. This compound was a leader agent in clinical use. Toxicity and resistance problems trigger the development of other platinum drugs with better clinical perspective and also raise the scientific interest for the putative antitumor properties of V, Ru and Cu compounds. Several scientific articles show that complexes of these metals are the new metal-based drugs used in the treatment of several cancers, such us, lung, colon, breast, bladder, etc. In this review we recapitulate current information and new advances on antitumor in vitro effects of several organic and inorganic compounds derived from copper, ruthenium and vanadium. These metal derived compounds targeting DNA or cell proteins involved in cell signaling pathways related to cancer. The mechanisms of cell death of these metallodrugs have also been comprehensibly reviewed. The knowledge of these mechanisms of death and the relationship between chemical structure and biological activity may be useful for the design of new metal-based drugs with promising pharmacologic applications as anticancer agents. PMID- 27554808 TI - The Role of NF-kB Inhibitors in Cell Response to Radiation. AB - It is well documented that ionizing radiation (IR) activates the transcription factor (NF-kappaB) which is a trigger for resistance cancer cells to treatment. It is involved in activation of pro-survival signaling pathways and resulting in cancer development and progression. In unstimulated condition, NF-kappaB is sequestered in cytoplasm but after the cell exposure to IR, proteasomal degradation of IkappaB flowing phosphorylation via IKK, leads to aberrantly NF kappaB activation and nuclear translocation. Therefore, interruption in IkappaB degradation, proteasome action, IKK phosphorylation and NF-kappaB nuclear translocation provide robust strategies for inhibiting adverse effect of IR induced NF-kappaB. In spite of uncompleted elucidation of NF-kappaB molecular mechanisms, different NF-kappaB inhibitors have been used in order to inhibiting the IR induced NF-kappaB. The aim of this review is to highlight the role of IR induced-NF-kappaB inhibitors such as MG132, bortezomib, curcumin, DHMEQ, naringin, sorafenib, genistein and parthenolide in suppression of IR induced NF kappaB adverse effects. Moreover, their chemical, structural characteristics and molecular mechanisms will be discussed. PMID- 27554809 TI - Crystal structure and functional characterization of a light-driven chloride pump having an NTQ motif. AB - A novel light-driven chloride-pumping rhodopsin (ClR) containing an 'NTQ motif' in its putative ion conduction pathway has been discovered and functionally characterized in a genomic analysis study of a marine bacterium. Here we report the crystal structure of ClR from the flavobacterium Nonlabens marinus S1-08(T) determined under two conditions at 2.0 and 1.56 A resolutions. The structures reveal two chloride-binding sites, one around the protonated Schiff base and the other on a cytoplasmic loop. We identify a '3 omega motif' formed by three non consecutive aromatic amino acids that is correlated with the B-C loop orientation. Detailed ClR structural analyses with functional studies in E. coli reveal the chloride ion transduction pathway. Our results help understand the molecular mechanism and physiological role of ClR and provide a structural basis for optogenetic applications. PMID- 27554810 TI - Response to "Response to Zhang et al.: Levetiracetam vs. brivaracetam for adults with refractory focal seizures: A meta-analysis and indirect comparison". PMID- 27554811 TI - Acute asthma, prognosis, and treatment. AB - Asthma affects about 300 million people globally and accounts for 1 in every 250 deaths in the world. Approximately 12 million people in the United States each year experience an acute exacerbation of their asthma, a quarter of which require hospitalization. Acute asthma should be differentiated from poor asthma control. Patients with acute asthma will exhibit increasing shortness of breath, chest tightness, coughing, and/or wheezing. In contrast, poor asthma control typically presents with a diurnal variability in airflow and is a characteristic that is usually not seen during an acute exacerbation. The history should include a review of comorbidities, adherence to medications, previous episodes of near fatal asthma, and whether the patient has experienced multiple emergency department visits or hospitalizations, particularly those requiring admission to an intensive care unit involving respiratory failure, intubation, and mechanical ventilation. Patient education is important to ensure that the patient understands that asthma is mostly a chronic disease and necessitates the avoidance of allergens, prevention of infections, adherence with routine vaccinations, management of comorbid conditions, and adherence to treatment regimens. This article is a structured review of the available literature regarding the diagnosis and management of acute asthma. PMID- 27554812 TI - Randomized controlled trial of early regular egg intake to prevent egg allergy. AB - BACKGROUND: The ideal age to introduce egg into the infant diet has been debated for the past 2 decades in the context of rising rates of egg allergy. OBJECTIVE: We sought to determine whether regular consumption of egg protein from age 4 to 6 months reduces the risk of IgE-mediated egg allergy in infants with hereditary risk, but without eczema. METHODS: Infants aged 4 to 6 months were randomly allocated to receive daily pasteurized raw whole egg powder (n = 407) or a color matched rice powder (n = 413) to age 10 months. All infants followed an egg-free diet and cooked egg was introduced to both groups at age 10 months. The primary outcome was IgE-mediated egg allergy defined by a positive pasteurized raw egg challenge and egg sensitization at age 12 months. RESULTS: There was no difference between groups in the percentage of infants with IgE-mediated egg allergy (egg 7.0% vs control 10.3%; adjusted relative risk, 0.75; 95% CI, 0.48 1.17; P = .20). A higher proportion of participants in the egg group stopped taking the study powder because of a confirmed allergic reaction (25 of 407 [6.1%] compared with 6 of 413 [1.5%]). Egg-specific IgG4 levels were substantially higher in the egg group at 12 months (median, 1.22 mgA/L vs control 0.07 mgA/L; P < .0001). CONCLUSIONS: We found no evidence that regular egg intake from age 4 to 6 months substantially alters the risk of egg allergy by age 1 year in infants who are at hereditary risk of allergic disease and had no eczema symptoms at study entry. PMID- 27554813 TI - Probiotic supplementation has little effect on peripheral blood regulatory T cells. PMID- 27554814 TI - Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. PMID- 27554815 TI - Age dictates a steroid-resistant cascade of Wnt5a, transglutaminase 2, and leukotrienes in inflamed airways. AB - BACKGROUND: Airway remodeling is a detrimental and refractory process showing age dependent clinical manifestations that are mechanistically undefined. The leukotriene (LT) and wingless/integrase (Wnt) pathways have been implicated in remodeling, but age-specific expression profiles and common regulators remained elusive. OBJECTIVE: We sought to study the activation of the LT and Wnt pathways during early- or late-onset allergic airway inflammation and to address regulatory mechanisms and clinical relevance in normal human bronchial epithelial cells (NHBEs) and nasal polyp tissues. METHODS: Mice were sensitized with house dust mite (HDM) allergens from days 3, 15, or 60 after birth. Remodeling factors in murine bronchoalveolar lavage fluid, lung tissue, or human nasal polyp tissue were analyzed by means of Western blotting, immunoassays, or histology. Regulatory mechanisms were studied in cytokine/HDM-stimulated NHBEs and macrophages. RESULTS: Bronchoalveolar lavage fluid LT levels were increased in neonatal and adult but reduced in juvenile HDM-sensitized mice. Lungs of neonatally sensitized mice showed increased 5-lipoxygenase levels, whereas adult mice expressed more group 10 secretory phospholipase A2, Wnt5a, and transglutaminase 2 (Tgm2). Older mice showed colocalization of Wnt5a and LT enzymes in the epithelium, a pattern also observed in human nasal polyps. IL-4 promoted epithelial Wnt5a secretion, which upregulated macrophage Tgm2 expression, and Tgm2 inhibition in turn reduced LT release. Tgm2, group 10 secretory phospholipase A2, and LT enzymes in NHBEs and nasal polyps were refractory to corticosteroids. CONCLUSION: Our findings reveal age differences in LT and Wnt pathways during airway inflammation and identify a steroid-resistant cascade of Wnt5a, Tgm2, and LTs, which might represent a therapeutic target for airway inflammation and remodeling. PMID- 27554816 TI - Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling. AB - BACKGROUND: Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. OBJECTIVE: We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. METHODS: We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n = 46,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. RESULTS: We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14-purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively-were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. CONCLUSION: We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs. PMID- 27554817 TI - Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-gamma. AB - BACKGROUND: CD40 ligand (CD40L) deficiency predisposes to opportunistic infections, including those caused by fungi and intracellular bacteria. Studies of CD40L-deficient patients reveal the critical role of CD40L-CD40 interaction for the function of T, B, and dendritic cells. However, the consequences of CD40L deficiency on macrophage function remain to be investigated. OBJECTIVES: We sought to determine the effect of CD40L absence on monocyte-derived macrophage responses. METHODS: After observing the improvement of refractory disseminated mycobacterial infection in a CD40L-deficient patient by recombinant human IFN gamma (rhIFN-gamma) adjuvant therapy, we investigated macrophage functions from CD40L-deficient patients. We analyzed the killing activity, oxidative burst, cytokine production, and in vitro effects of rhIFN-gamma and soluble CD40 ligand (sCD40L) treatment on macrophages. In addition, the effect of CD40L absence on the macrophage transcriptome before and after rhIFN-gamma treatment was studied. RESULTS: Macrophages from CD40L-deficient patients exhibited defective fungicidal activity and reduced oxidative burst, both of which improved in the presence of rhIFN-gamma but not sCD40L. In contrast, rhIFN-gamma and sCD40L ameliorate impaired production of inflammatory cytokines. Furthermore, rhIFN-gamma reversed defective control of Mycobacterium tuberculosis proliferation by patients' macrophages. The absence of CD40L dysregulated the macrophage transcriptome, which was improved by rhIFN-gamma. Additionally, rhIFN-gamma increased expression levels of pattern recognition receptors, such as Toll-like receptors 1 and 2, dectin 1, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin in macrophages from both control subjects and patients. CONCLUSION: Absence of CD40L impairs macrophage development and function. In addition, the improvement of macrophage immune responses by IFN-gamma suggests this cytokine as a potential therapeutic option for patients with CD40L deficiency. PMID- 27554819 TI - Exploiting CD22 on antigen-specific B cells to prevent allergy to the major peanut allergen Ara h 2. PMID- 27554818 TI - IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. AB - BACKGROUND: Atopic dermatitis (AD) is characterized by intense pruritis and is a common childhood inflammatory disease. Many factors are known to affect AD development, including the pleiotropic cytokine IL-4. Yet little is known regarding the direct effects of IL-4 on keratinocyte function. OBJECTIVE AND METHODS: In this report RNA sequencing and functional assays were used to define the effect of the allergic environment on primary keratinocyte function and wound repair in mice. RESULTS: Acute or chronic stimulation by IL-4 modified expression of more than 1000 genes expressed in human keratinocytes that are involved in a broad spectrum of nonoverlapping functions. Among the IL-4-induced changes, repression of fibronectin critically impaired the human keratinocyte wound response. Moreover, in mouse models of spontaneous and induced AD-like lesions, there was delayed re-epithelialization. Importantly, topical treatment with fibronectin restored the epidermal repair response. CONCLUSION: Keratinocyte gene expression is critically shaped by IL-4, altering cell fate decisions, which are likely important for the clinical manifestations and pathology of allergic skin disease. PMID- 27554820 TI - Allergy-related disease in relation to early life exposures-the ALADDIN birth cohort. PMID- 27554822 TI - Dedicator of cytokinesis 8-deficient CD4+ T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells. AB - BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4+ T cells to disease pathogenesis in these patients has not been thoroughly investigated. OBJECTIVE: We sought to investigate the phenotype and function of DOCK8-deficient CD4+ T cells to determine (1) intrinsic and extrinsic CD4+ T-cell defects and (2) how defects account for the clinical features of DOCK8 deficiency. METHODS: We performed in-depth analysis of the CD4+ T-cell compartment of DOCK8-deficient patients. We enumerated subsets of CD4+ T helper cells and assessed cytokine production and transcription factor expression. Finally, we determined the levels of IgE specific for staple foods and house dust mite allergens in DOCK8-deficient patients and healthy control subjects. RESULTS: DOCK8-deficient memory CD4+ T cells were biased toward a TH2 type, and this was at the expense of TH1 and TH17 cells. In vitro polarization of DOCK8-deficient naive CD4+ T cells revealed the TH2 bias and TH17 defect to be T-cell intrinsic. Examination of allergen-specific IgE revealed plasma IgE from DOCK8-deficient patients is directed against staple food antigens but not house dust mites. CONCLUSION: Investigations into the DOCK8 deficient CD4+ T cells provided an explanation for some of the clinical features of this disorder: the TH2 bias is likely to contribute to atopic disease, whereas defects in TH1 and TH17 cells compromise antiviral and antifungal immunity, respectively, explaining the infectious susceptibility of DOCK8-deficient patients. PMID- 27554823 TI - Mendelian randomization analysis demonstrates that low vitamin D is unlikely causative for pediatric asthma. PMID- 27554821 TI - An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis. AB - BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking because the underlying molecular basis is poorly understood. OBJECTIVE: We sought to characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsy specimens from 21 genotyped patients with ichthyosis (congenital ichthyosiform erythroderma, n = 6; lamellar ichthyosis, n = 7; epidermolytic ichthyosis, n = 5; and Netherton syndrome, n = 3) using immunohistochemistry and RT-PCR and compared them with specimens from healthy control subjects, patients with atopic dermatitis (AD), and patients with psoriasis. Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); transepidermal water loss; and pruritus. RESULTS: Ichthyosis samples showed increased epidermal hyperplasia (increased thickness and keratin 16 expression) and T-cell and dendritic cell infiltrates. Increases of general inflammatory (IL-2), innate (IL-1beta), and some TH1/interferon (IFN gamma) markers in patients with ichthyosis were comparable with those in patients with psoriasis or AD. TNF-alpha levels in patients with ichthyosis were increased only in those with Netherton syndrome but were much lower than in patients with psoriasis and those with AD. Expression of TH2 cytokines (IL-13 and IL-31) was similar to that seen in control subjects. The striking induction of IL-17-related genes or markers synergistically induced by IL-17 and TNF-alpha (IL-17A/C, IL-19, CXCL1, PI3, CCL20, and IL36G; P < .05) in patients with ichthyosis was similar to that seen in patients with psoriasis. IASI and IASI-E scores strongly correlated with IL-17A (r = 0.74, P < .001) and IL-17/TNF-synergistic/additive gene expression. These markers also significantly correlated with transepidermal water loss, suggesting a link between the barrier defect and inflammation in patients with ichthyosis. CONCLUSION: Our data associate a shared TH17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17-targeting strategies. PMID- 27554824 TI - Using mobile devices for inpatient rounding and handoffs: an innovative application developed and rapidly adopted by clinicians in a pediatric hospital. AB - Objective: To describe the usage of a novel application (The FLOW) that allows mobile devices to be used for rounding and handoffs. Materials and Methods: The FLOW provides a view of patient data and the capacity to enter short notes via personal mobile devices. It was deployed using a "bring-your-own-device" model in 4 pilot units. Social network analysis (SNA) was applied to audit trails in order to visualize usage patterns. A questionnaire was used to describe user experience. Results: Overall, 253 health professionals used The FLOW with their personal mobile devices from October 2013 to March 2015. In pediatric and neonatal intensive care units (ICUs), a median of 26-26.5 notes were entered per user per day. Visual network representation of app entries showed that usage patterns were different between the ICUs. In 127 questionnaires (50%), respondents reported using The FLOW most often to enter notes and for handoffs. The FLOW was perceived as having improved patient care by 57% of respondents, compared to usual care. Most respondents (86%) wished to continue using The FLOW. Discussion: This study shows how a handoff and rounding tool was quickly adopted in pediatric and neonatal ICUs in a hospital setting where patient charts were still paper-based. Originally developed as a tool to support informal documentation using smartphones, it was adapted to local practices and expanded to print sign-out documents and import notes within the medicolegal record with desktop computers. Interestingly, even if not supported by the nursing administrative authorities, the level of use for data entry among nurses and doctors was similar in all units, indicating close collaboration in documentation practices in these ICUs. PMID- 27554826 TI - Gastrointestinal tract obstruction secondary to post-operative oedema: does dexamethasone administration help? AB - Oedema can occur in handled tissues following upper gastrointestinal surgery with anastomosis formation. Obstruction of the lumen may result in delayed return of enteric function. Intravenous steroid use may be beneficial. Three cases of delayed emptying following fundoplication, gastro-enteric and entero-enteric anastomoses are reviewed. Conservative management with supportive measures failed. Dexamethasone was administered to treat the oedematous obstruction. A literature review in PubMed, Cochrane database and Medline for English language publications on the use of dexamethasone in the treatment of acute post surgical oedema of the upper gastrointestinal was conducted. Administration of dexamethasone led to resolution of symptoms and successful outcome. No reports on the use of steroids in this context were identified in the literature. The use of dexamethasone may effectively treat intestinal obstruction due to inflammatory or oedematous cause in the early post-operative period. PMID- 27554825 TI - International health IT benchmarking: learning from cross-country comparisons. AB - Objective: To pilot benchmark measures of health information and communication technology (ICT) availability and use to facilitate cross-country learning. Materials and Methods: A prior Organization for Economic Cooperation and Development-led effort involving 30 countries selected and defined functionality based measures for availability and use of electronic health records, health information exchange, personal health records, and telehealth. In this pilot, an Organization for Economic Cooperation and Development Working Group compiled results for 38 countries for a subset of measures with broad coverage using new and/or adapted country-specific or multinational surveys and other sources from 2012 to 2015. We also synthesized country learnings to inform future benchmarking. Results: While electronic records are widely used to store and manage patient information at the point of care-all but 2 pilot countries reported use by at least half of primary care physicians; many had rates above 75%-patient information exchange across organizations/settings is less common. Large variations in the availability and use of telehealth and personal health records also exist. Discussion: Pilot participation demonstrated interest in cross-national benchmarking. Using the most comparable measures available to date, it showed substantial diversity in health ICT availability and use in all domains. The project also identified methodological considerations (e.g., structural and health systems issues that can affect measurement) important for future comparisons. Conclusion: While health policies and priorities differ, many nations aim to increase access, quality, and/or efficiency of care through effective ICT use. By identifying variations and describing key contextual factors, benchmarking offers the potential to facilitate cross-national learning and accelerate the progress of individual countries. PMID- 27554827 TI - Acute colonic pseudo-obstruction (Ogilvie's syndrome) with caecal perforation after caesarean section. AB - Ogilvie syndrome or acute colonic pseudo-obstruction is characterized by acute dilatation of the colon usually involving caecum and right hemi-colon in the absence of any mechanical obstruction. It is usually associated with an underlying severe illness/infection or surgery, mostly caesarean section and rarely occurs spontaneously. Identification of this condition is important due to the increased risk of bowel ischaemia and perforation particularly with caecal diameter >9 cm. This is a case report of bowel perforation following caesarean section leading to urgent laparotomy. PMID- 27554828 TI - Acute small bowel obstruction due to a large intraluminal blood clot after laparoscopic Roux-en-Y gastric bypass. AB - Small bowel obstructions (SBOs) are a known perioperative complication of laparoscopic Roux-en-Y gastric bypass and common etiologies include internal hernia, port site hernia, jejunojejunostomy stricture, ileus and adhesions. Less commonly, SBO can be caused by superior mesenteric artery syndrome, intussusception and intraluminal blood clot. We present a case of SBO caused by intraluminal blood clot from jejunojejunostomy staple line bleeding in a patient with a normal coagulation profile. Computed tomography was used to elucidate the cause of perioperative SBO, and diagnostic laparoscopy was used to both diagnose and treat the complication. In this case, the intraluminal clot was evacuated laparoscopically by enterotomy, thrombectomy and primary closure without anastomotic revision since there was no evidence of continued bleeding. Administration of enoxaparin and Toradol post-operatively may have exacerbated mild intraluminal bleeding occurring at the stapled jejunojejunal anastomosis. Prompt recognition and treatment of perioperative SBO can prevent catastrophic consequences related to bowel perforation. PMID- 27554829 TI - Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula. AB - The interrelation of depression and pain is increasingly coming under scrutiny. Although the lateral habenula (LHb) is widely implicated in the pathogenesis of depression and pain, its role in the interaction of depression and pain remains unknown. Thus, the aim of current study was to investigate the role of LHb in rat depression-pain comorbidity. Single extracellular firing recording and immunofluorescence methods were used to compare firing rates and c-Fos expression of the LHb neurons in normal and model rats. Following subcutaneous injection of formalin into the hind paw to simulate natural pain, we assessed pain behavior in rats subjected to the chronic, unpredictable mild stress procedure (CUMS, a model of depression). Pain sensitivity in the model rats was increased over that of controls. These rats showed a significant increase in the firing activity of LHb neurons compared with normal rats. Significantly, about 73% of neurons with high discharge frequency in LHb of model rats were pain-activated neurons (PANs), and the firing rates of PANs were inhibited by intraperitoneal injection of a tricyclic antidepressant, clomipramine. Immunofluorescence showed that the percentage of c-Fos positive cells in LHb was significantly increased in rats receiving CUMS alone, rats receiving pain stimulation alone, and rats receiving both CUMS and pain stimulation, but especially the last. The interaction effect was inhibited by injection of clomipramine. The LHb lesion can improve both depression-like behavior and pain sensitivity in depression model rats with pain. These suggest that hyperactivity of the LHb neurons contributes to depression pain comorbidity in rats. PMID- 27554832 TI - Drug appraisal issues must be resolved at policy level. PMID- 27554830 TI - Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2. AB - Psoriatic arthritis (PsA) patients have increased risk of both atherosclerosis and osteoporosis. Previous studies revealed that IL-33/ST2 axis may be related to both conditions; however, these associations were never evaluated in a single patients' group. Here we explored the association among plasma levels of IL-33 and its decoy receptor soluble ST2 (sST2), carotid plaque determined by ultrasound, and volumetric bone mineral density (vBMD)/microstructure of distal radius measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 80 PsA patients (55% male; 53.0 +/- 10.1 years). Plasma sST2 levels were significantly higher in 33 (41%) patients with carotid plaques (11.2 +/- 4.5 vs 7.7 +/- 3.7 ng/ml, P < 0.001). In multivariate analysis, sST2 was an independent explanatory variable associated with carotid plaques (OR = 1.296, 95% CI: [1.091,1.540]; P = 0.003). After adjustment for the osteoporotic risk factors, sST2 was significantly associated with higher cortical porosity (beta = 0.184, [0.042,0.325]; P = 0.012) and cortical pore volume (2.247, [0.434,4.060]; P = 0.016); and had a trend to be associated with lower cortical vBMD (-2.918, [ 6.111,0.275]; P = 0.073). IL-33 was not associated with carotid plaque or vBMD/microstructure. In conclusion, plasma sST2 levels were independently correlated with both carotid plaque and compromised cortical vBMD/microstructure in PsA patients. IL-33/ST2 axis may be a link between accelerated atherosclerosis and osteoporosis in PsA. PMID- 27554833 TI - Missing patients in "Major Trauma Registry" of Navarre: incidence and pattern. AB - BACKGROUND: Trauma registries (TR) collect information about trauma patients according to inclusion criteria, and it helps to establish protocols to improve care. However, all TR deal with incompleteness. The aim of this study is to assess the number of patients not included despite fulfilling inclusion criteria in our regional TR and identifying the predictors for being missing. METHODS: The sample was randomly selected. Two months of each year from 2010 to 2014 (5 years) were selected, and medical files of all patients attended in the emergency department room during those months were studied. Patients who were already correctly included in the TR were assigned to the 'included' group, and patients who should have been but were not to the 'missing' group. The multivariable logistic regression analysis was performed to identify predictors for being missed from the TR. RESULTS: Of a total of 200, 79 (40 % approximately) were identified as missing. We defined the characteristic profiles of missing patients and found that the hospital RTS and the number of injuries are independent predictors to be missing in our trauma registry, with an adjusted odds ratio of 1844 [95 % (1092-3114) and 0.574 (95 % CI 0.428-0.770)], respectively. CONCLUSIONS: Overall, 40 % of the patients who met the inclusion criteria of the TR were not included in the registry. Our results can be generalized to other trauma records based on Utstein style, because we think probably that this fact is also happening in other databases. PMID- 27554834 TI - Leishmania-FAST15: A rapid, sensitive and low-cost real-time PCR assay for the detection of Leishmania infantum and Leishmania braziliensis kinetoplast DNA in canine blood samples. AB - We describe an improved real-time PCR assay (designated as "Leishmania-FAST15") for the detection and quantification of Leishmania infantum and Leishmania braziliensis kinetoplast DNA minicircles in canine blood samples. The analytical sensitivity of this technique is 0.1 fg of DNA, which is equivalent to 0.002 parasite per reaction. This assay uses a small reaction volume (15 MUl) and is rapid to perform, with the results being available in less than 34 min. This improved assay might also be suitable for detecting and quantifying L. infantum and L. braziliensis DNA in other tissues, such as bone marrow and lymph nodes. PMID- 27554835 TI - Nivolumab-Induced Pericardial Tamponade: A Case Report and Discussion. AB - Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life threatening immune-related side effects may still occur and clinical vigilance is required. PMID- 27554836 TI - Diagnosis, treatment, and monitoring of dry eye disease. PMID- 27554837 TI - "Just This Breath..." How Mindfulness Meditation Can Shift Everything, Including Neural Connectivity. PMID- 27554838 TI - Genetic Risk for Lung Cancer and the Benefits of Quitting Smoking. PMID- 27554840 TI - Corrigendum to "One of the Immune Activation Profiles Observed in HIV-1-Infected Adults with Suppressed Viremia is Linked to Metabolic Syndrome: The ACTIVIH Study" [EBioMedicine 8 (2016) 265-276]. PMID- 27554839 TI - Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants. AB - BACKGROUND: Respiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanisms remain unclear. METHODS: We infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates. FINDINGS: GWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV. INTERPRETATION: Translational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies). PMID- 27554841 TI - ALK rearrangements-associated renal cell carcinoma (RCC) with unique pathological features in an adult. AB - We report an exceptional case of renal cell carcinoma (RCC) associated with ALK translocation in an adult. The tumor was located in the left kidney and measured 4cm. The tumor was composed of sheets of large eosinophilic cells with frequently intracytoplasmic vacuoles. The nuclei were large with a nucleolar grade 3. At immunohistochemistry, tumor cells were diffusely positive for PAX8 and vimentin and focally stained with CK7. ALK immunostaining was diffuse and fluorescent in situ hybridization showed a rearrangement of ALK in numerous tumor cells. To date, less than 17 cases of RCCs with ALK rearrangements are reported in children and adults. The prognosis remains uncertain but ALK rearrangement may be of potential value for target therapy with crizotinib. PMID- 27554842 TI - Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. METHODS: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion. RESULTS: A systematic review revealed 10 eligible publications. Sotalol was superior to placebo and/or no antiarrhythmic therapy in AF conversion, with a relative success of 24 (95% CI 4.7-119, p < 0.001). Sotalol was not significantly different from class IA antiarrhythmic drugs. Similarly, sotalol was not different from class IC antiarrhythmic drugs or amiodarone in terms of conversion efficacy. In one study, sotalol was less effective than high dose ibutilide (2 mg), with a relative success of 0.248 (95% CI 0.128-0.481, p < 0.001). Ibutilide caused more proarrhythmia. CONCLUSIONS: Sotalol is as effective as class IA and class IC antiarrhythmic agents, and it is also as effective as amiodarone for pharmacologic conversion of AF. Only ibutilide at a high dose showed a greater conversion rate of AF. PMID- 27554843 TI - Dissection of the HOG pathway activated by hydrogen peroxide in Saccharomyces cerevisiae. AB - Cells usually cope with oxidative stress by activating signal transduction pathways. In the budding yeast Sacchromyces cerevisiae, the high osmolarity glycerol (HOG) pathway has long been implicated in transducing the oxidative stress-induced signal, but the underlying mechanisms are not well defined. Based on phosphorylation of the mitogen-activated protein kinase (MAPK) Hog1, we reveal that the signal from hydrogen peroxide (H2 O2 ) flows through Ssk1, the response regulator of the two-component system of the HOG pathway. Downstream signal transduction into the HOG MAPK cascade requires the MAP kinase kinase kinase (MAP3K) Ssk2 but not its paralog Ssk22 or another MAP3K Ste11 of the pathway, culminating in Hog1 phosphorylation via the MAP2K Pbs2. When overexpressed, Ssk2 is also activated in an Ssk1-independent manner. Unlike in mammals, H2 O2 does not cause endoplasmic reticulum stress, which can activate Hog1 through the conventional unfolded protein response. Hog1 activated by H2 O2 is retained in the cytoplasm, but is still able to activate the cAMP- or stress-responsive elements by unknown mechanisms. PMID- 27554844 TI - On the domains of T4 phage sliding clamp gp45: An intermolecular crosstalk governs structural stability and biological activity. AB - BACKGROUND: DNA polymerase processivity factors are ubiquitously present in all living organisms. Notwithstanding their high significance, the molecular details of clamps pertaining to the factors contributing to their stability are presently lacking. The bacteriophage T4 sliding clamp gp45 forms a homotrimer that besides being involved in DNA replication, moonlights as a transcription factor. Here we have carried out a detailed characterization of gp45 to understand the role of monomer-monomer interface interactions in stability and functioning of the protein. METHODS: We generated several gp45 mutants harboring either Ala or Pro substitutions at the interface residues and performed a detailed investigation using biochemical and biophysical methods including circular dichroism, fluorescence anisotropy and quenching, differential scanning calorimetry, blue native PAGE, cross-linking, size exclusion chromatography, and dynamic light scattering. We also carried out both transcription and DNA replication to understand the properties of the wild-type and the mutant proteins. RESULTS: One specific mutation S88P leads not only to monomerization, but also results in an unstable molecule. Most interestingly, mutating either Q125 or K164 in the gp45 C terminal domain negatively affects the stability of the N-terminal domain. We also report that these residues upon mutation to alanine make gp45 inactive for late promoter transcription, whereas strand-displacement DNA replication ability remains unaltered. CONCLUSIONS AND GENERAL SIGNIFICANCE: The results suggest that the two domains of gp45 demonstrate an "inter-monomer" crosstalk that stabilizes the trimer. We also conclude that the residue-specific interactions at the interface allow the protein to function distinctly as replication and transcription factors. PMID- 27554846 TI - The tip and hidden part of the iceberg: Proteinogenic and non-proteinogenic aliphatic amino acids. AB - BACKGROUND: Amino acids are the essential building blocks of proteins and, therefore, living organisms. While the focus often lies on the canonical or proteinogenic amino acids, there is also a large number of non-canonical amino acids to explore. Some of them are part of toxins or antibiotics in fungi, bacteria or animals (e.g. sponges). Some others operate at the translational level like an "undercover agent". SCOPE OF REVIEW: Here we give an overview of natural aliphatic amino acids, up to a side chain length of five carbons, without rings and with an unmodified backbone, and have a closer look on each of them. Some of them are dehydro amino acids with double or even triple bonds. Moreover, we outline mathematical methods for enumerating the complete list of all potential aliphatic amino acids of a given chain length. This should be of interest for synthetic biology. MAJOR CONCLUSIONS: Most non-proteinogenic amino acids are found within fungi, with particularly many produced by Amanita species as defence chemicals. Several are incorporated into peptide antibiotics. Some of the amino acids occur due to broad substrate specificity of the branched-chain amino acid synthesis pathways. A large variety of amino acids were also found in the Murchison meteorite. GENERAL SIGNIFICANCE: Non-proteinogenic amino acids are of interest for numerous medical applications: discovery of new antibiotics, support in designing synthetic antibiotics, improvement of protein and peptide pharmaceuticals by avoiding incorporation of non-canonical amino acids, study of toxic cyanobacteria and other applications. PMID- 27554845 TI - A novel role for small molecule glycomimetics in the protection against lipid induced endothelial dysfunction: Involvement of Akt/eNOS and Nrf2/ARE signaling. AB - BACKGROUND: Glycomimetics are a diverse array of saccharide-inspired compounds, designed to mimic the bioactive functions of glycosaminoglycans. Therefore, glycomimetics represent a unique source of novel therapies to target aberrant signaling and protein interactions in a wide range of diseases. We investigated the protective effects of four newly synthesized small molecule glycomimetics against lipid-induced endothelial dysfunction, with an emphasis on nitric oxide (NO) and oxidative stress. METHODS: Four aromatic sugar mimetics were synthesized by the stepwise transformation of 2,5-dihydroxybenzoic acid to derivatives (C1 C4) incorporating sulfate groups to mimic the structure of heparan sulfate. RESULTS: Glycomimetic-treated human umbilical vein endothelial cells (HUVECs) were exposed to palmitic acid to model lipid-induced oxidative stress. Palmitate induced impairment of NO production was restored by the glycomimetics, through activation of Akt/eNOS signaling. Furthermore, C1-C4 significantly inhibited palmitate-induced reactive oxygen species (ROS) production, lipid peroxidation, and activity and expression of NADPH oxidase. These effects were attributed to activation of the Nrf2/ARE pathway and downstream activation of cellular antioxidant and cytoprotective proteins. In ex vivo vascular reactivity studies, the glycomimetics (C1-C4) also demonstrated a significant improvement in endothelium-dependent relaxation and decreased ROS production and NADPH oxidase activity in isolated mouse thoracic aortic rings exposed to palmitate. CONCLUSIONS: The small molecule glycomimetics, C1-C4, protect against lipid induced endothelial dysfunction through up-regulation of Akt/eNOS and Nrf2/ARE signaling pathways. Thus, carbohydrate-derived therapeutics are a new class of glycomimetic drugs targeting endothelial dysfunction, regarded as the first line of defense against vascular complications in cardiovascular disease. PMID- 27554847 TI - Interpersonal violence and synthetic cannabinoids. PMID- 27554848 TI - Ipsilateral full-thickness skin grafts to repair the donor site defect of a radial forearm free flap: a reflection on technique. PMID- 27554849 TI - From Obesity Resistance to Obesity Prediction and Prevention? PMID- 27554851 TI - Biochemical and biophysical approaches to study the structure and function of the chloride channel (ClC) family of proteins. AB - The chloride channel (ClC) protein family comprises both chloride (Cl(-)) channels and chloride/proton (Cl(-)/H(+)) antiporters. In prokaryotes and eukaryotes, these proteins mediate the movement of Cl(-) ions across the membrane. In eukaryotes, ClC proteins play a role in the stabilization of membrane potential, epithelial ion transport, hippocampal neuroprotection, cardiac pacemaker activity and vesicular acidification. Moreover, mutations in the genes encoding ClC proteins can cause genetic disease in humans. In prokaryotes, the Cl(-)/H(+) antiporters, such as ClC-ec1 found in Escherichia coli promote proton expulsion in the extreme acid-resistance response common to enteric bacteria. To date, structural and functional studies of the prokaryotic protein have revealed unique structural features, including complicated transmembrane topology with 18 alpha-helices in each subunit and an anion coordinating region in each subunit. Several different approaches such as X-ray crystallography, NMR, biochemical studies, and molecular dynamics simulations have been applied to the study of ClC proteins. Continued study of the unique structure and function of this diverse family of proteins has the potential to lead to the development of novel therapeutic targets for neuronal, renal, bone, and food-borne diseases. PMID- 27554850 TI - Efficient Pathway for the Preparation of Aryl(isoquinoline)iodonium(III) Salts and Synthesis of Radiofluorinated Isoquinolines. AB - Iodonium compounds play a pivotal role in (18) F-fluorination of radiopharmaceuticals containing non-activated arenes. However, preparation of these species is limited to oxidation conditions or exchange with organometallics that are prepared from aryl halides. Herein we describe a novel "one-pot" process to assemble aryl(isoquinoline)iodonium salts in 40-94 % yields from mesoionic carbene silver complex and Aryl-I-Py2 (OTf)2 . The method is general, practical, and compatible with well-functionalized molecules as well as useful for the preparation of a wide range of (18) F-labeled isoquinolines resulting in up to 92 % radiochemical conversion. As proof of concept, a fluorinated isoquinoline alkaloid, (18) F-aspergillitine is prepared in 10 % isolated radiochemical yield from the corresponding phenyl(aspergillitine)iodonium salt. PMID- 27554852 TI - Emerging spotted fever group rickettsiae in ticks, northwestern China. AB - We report Rickettsia conorii subsp. indica, Candidatus R. barbariae and R. massiliae in Rhipicephalus turanicus from sheep around the Taklamakan desert, northwestern China. The topology of the phylogenetic trees produced from the maximum likelihood (ML) analyses of the ompA-gltA-rrs-geneD-ompB concatenated sequence data was very similar to that of the neighbor joining (NJ) tree, and with total support of 69%-100% bootstrap values for the inclusion of the rickettsiae in Rh. turanicus within the clade that contained R. conorii subsp. indica; Candidatus R. barbariae and Rickettsia sp. Tselentii; R. massiliae str. AZT80; and R. massiliae MTU5, respectively. Studies suggest that the co-existence of these spotted fever group rickettsiae is a threat to public health in China. Work is important in exploring novel and emerging pathogens. PMID- 27554853 TI - Heme-Oxygenase I and PCG-1alpha Regulate Mitochondrial Biogenesis via Microglial Activation of Alpha7 Nicotinic Acetylcholine Receptors Using PNU282987. AB - AIMS: A loss in brain acetylcholine and cholinergic markers, subchronic inflammation, and impaired mitochondrial function, which lead to low-energy production and high oxidative stress, are common pathological factors in several neurodegenerative diseases (NDDs). Glial cells are important for brain homeostasis, and microglia controls the central immune response, where alpha7 acetylcholine nicotinic receptors (nAChR) seem to play a pivotal role; however, little is known about the effects of this receptor in metabolism. Therefore, the aim of this study was to evaluate if glial mitochondrial energetics could be regulated through alpha7 nAChR. RESULTS: Primary glial cultures treated with the alpha7 nicotinic agonist PNU282987 increased their mitochondrial mass and their mitochondrial oxygen consumption without increasing oxidative stress; these changes were abolished when nuclear erythroid 2-related factor 2 (Nrf2) was absent, heme oxygenase-1 (HO-1) was inhibited, or peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) was silenced. More specifically, microglia of animals treated intraperitoneally with the alpha7 nAChR agonist PNU282987 (10 mg/kg) showed a significant increase in mitochondrial mass. Interestingly, LysMcre-Hmox1Delta/Delta and PGC-1alpha-/- animals showed lower microglial mitochondrial levels and treatment with PNU282987 did not produce effects on mitochondrial levels. INNOVATION: Increases in microglial mitochondrial mass and metabolism can be achieved via alpha7 nAChR by a mechanism that implicates Nrf2, HO-1, and PGC-1alpha. This signaling pathway could open a new strategy for the treatment of NDDs, such as Alzheimer's, characterized by a reduction of cholinergic markers. CONCLUSION: alpha7 nAChR signaling increases glial mitochondrial mass, both in vitro and in vivo, via HO-1 and PCG-1alpha. These effects could be of potential benefit in the context of NDDs. Antioxid. Redox Signal. 27, 93-105. PMID- 27554854 TI - Evaluation of an Axial Pattern Flap Based on the Cranial Cutaneous Branch of the Saphenous Artery: A Cadaveric Perfusion Study. AB - OBJECTIVES: To confirm the anatomic location of the cranial cutaneous branch of the saphenous artery (CCSA), delineate the angiosome of the CCSA, and provide guidelines for clinical use of an axial pattern flap based on the CCSA. STUDY DESIGN: Anatomic study. ANIMALS: Greyhound cadavers (n=10). METHODS: Shortly after euthanasia, the CCSA was identified and isolated in each hindlimb. Methylene blue and radiographic perfusion studies were performed. The skin was freed from the thigh for photographic and radiographic images. The dimensions of the skin area suitable for use as an axial pattern flap were related to anatomical landmarks. Mock surgical elevation and transposition of the flap in 2 dogs allowed assessment of flap mobility and ease of donor site closure for clinical use. RESULTS: The CCSA was reliably identified in all dogs branching from the saphenous artery as it became superficial to the sartorius muscle, immediately distal to the caudal cutaneous branch and proximal to the genicular branches. Genicular branches were variably paired or singular. Perfusion studies defined the CCSA angiosome as the area cranial to the saphenous artery and caudal to the cranial border of the thigh, extending proximally from the level of the medial tibial condyle to two-thirds of the distance to the inguinal ring. CONCLUSION: An axial pattern flap based on the CCSA could be expected to cover skin defects of the cranial aspect of the distal thigh and stifle, the popliteal region caudal to the stifle, and the proximal medial crus. PMID- 27554856 TI - Modulators of Stomatal Lineage Signal Transduction Alter Membrane Contact Sites and Reveal Specialization among ERECTA Kinases. AB - Signal transduction from a cell's surface to its interior requires dedicated signaling elements and a cellular environment conducive to signal propagation. Plant development, defense, and homeostasis rely on plasma membrane receptor-like kinases to perceive endogenous and environmental signals, but little is known about their immediate downstream targets and signaling modifiers. Using genetics, biochemistry, and live-cell imaging, we show that the VAP-RELATED SUPPRESSOR OF TMM (VST) family is required for ERECTA-mediated signaling in growth and cell fate determination and reveal a role for ERECTA-LIKE2 in modulating signaling by its sister kinases. We show that VSTs are peripheral plasma membrane proteins that can form complexes with integral ER-membrane proteins, thereby potentially influencing the organization of the membrane milieu to promote efficient and differential signaling from the ERECTA-family members to their downstream intracellular targets. PMID- 27554855 TI - Hedgehog Signal Transduction: Key Players, Oncogenic Drivers, and Cancer Therapy. AB - The Hedgehog (Hh) signaling pathway governs complex developmental processes, including proliferation and patterning within diverse tissues. These activities rely on a tightly regulated transduction system that converts graded Hh input signals into specific levels of pathway activity. Uncontrolled activation of Hh signaling drives tumor initiation and maintenance. However, recent entry of pathway-specific inhibitors into the clinic reveals mixed patient responses and thus prompts further exploration of pathway activation and inhibition. In this review, we share emerging insights into regulated and oncogenic Hh signaling, supplemented with updates on the development and use of Hh pathway-targeted therapies. PMID- 27554857 TI - Fascin Regulates Nuclear Movement and Deformation in Migrating Cells. AB - Fascin is an F-actin-bundling protein shown to stabilize filopodia and regulate adhesion dynamics in migrating cells, and its expression is correlated with poor prognosis and increased metastatic potential in a number of cancers. Here, we identified the nuclear envelope protein nesprin-2 as a binding partner for fascin in a range of cell types in vitro and in vivo. Nesprin-2 interacts with fascin through a direct, F-actin-independent interaction, and this binding is distinct and separable from a role for fascin within filopodia at the cell periphery. Moreover, disrupting the interaction between fascin and nesprin-2 C-terminal domain leads to specific defects in F-actin coupling to the nuclear envelope, nuclear movement, and the ability of cells to deform their nucleus to invade through confined spaces. Together, our results uncover a role for fascin that operates independently of filopodia assembly to promote efficient cell migration and invasion. PMID- 27554858 TI - aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization. AB - Atypical protein kinase C (aPKC) is a key apical-basal polarity determinant and Par complex component. It is recruited by Par3/Baz (Bazooka in Drosophila) into epithelial apical domains through high-affinity interaction. Paradoxically, aPKC also phosphorylates Par3/Baz, provoking its relocalization to adherens junctions (AJs). We show that Par3 conserved region 3 (CR3) forms a tight inhibitory complex with a primed aPKC kinase domain, blocking substrate access. A CR3 motif flanking its PKC consensus site disrupts the aPKC kinase N lobe, separating P loop/alphaB/alphaC contacts. A second CR3 motif provides a high-affinity anchor. Mutation of either motif switches CR3 to an efficient in vitro substrate by exposing its phospho-acceptor site. In vivo, mutation of either CR3 motif alters Par3/Baz localization from apical to AJs. Our results reveal how Par3/Baz CR3 can antagonize aPKC in stable apical Par complexes and suggests that modulation of CR3 inhibitory arms or opposing aPKC pockets would perturb the interaction, promoting Par3/Baz phosphorylation. PMID- 27554861 TI - Analysis authors reply to Response by Corrado and colleagues. PMID- 27554859 TI - Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos. AB - Embryos of most metazoans undergo rapid and synchronous cell cycles following fertilization. While diffusion is too slow for synchronization of mitosis across large spatial scales, waves of Cdk1 activity represent a possible process of synchronization. However, the mechanisms regulating Cdk1 waves during embryonic development remain poorly understood. Using biosensors of Cdk1 and Chk1 activities, we dissect the regulation of Cdk1 waves in the Drosophila syncytial blastoderm. We show that Cdk1 waves are not controlled by the mitotic switch but by a double-negative feedback between Cdk1 and Chk1. Using mathematical modeling and surgical ligations, we demonstrate a fundamental distinction between S phase Cdk1 waves, which propagate as active trigger waves in an excitable medium, and mitotic Cdk1 waves, which propagate as passive phase waves. Our findings show that in Drosophila embryos, Cdk1 positive feedback serves primarily to ensure the rapid onset of mitosis, while wave propagation is regulated by S phase events. PMID- 27554860 TI - A Transcriptional Lineage of the Early C. elegans Embryo. AB - During embryonic development, cells must establish fates, morphologies, and behaviors in coordination with one another to form a functional body. A prevalent hypothesis for how this coordination is achieved is that each cell's fate and behavior is determined by a defined mixture of RNAs. Only recently has it become possible to measure the full suite of transcripts in a single cell. Here we quantify genome-wide mRNA abundance in each cell of the Caenorhabditis elegans embryo up to the 16-cell stage. We describe spatially dynamic expression, quantify cell-specific differential activation of the zygotic genome, and identify genes that were previously unappreciated as being critical for development. We present an interactive data visualization tool that allows broad access to our dataset. This genome-wide single-cell map of mRNA abundance, alongside the well-studied life history and fate of each cell, describes at a cellular resolution the mRNA landscape that guides development. PMID- 27554862 TI - Making Sense of Bereavement in People with Profound Intellectual and Multiple Disabilities: Carer Perspectives. AB - BACKGROUND: People with intellectual disabilities are thought to have a reduced capacity for understanding death. Drawing on cognitive theory, researchers have suggested that those with profound intellectual and multiple disabilities mainly perceive loss as a mismatch between past and present experiences. However, very little research has considered how carers conceptualize bereavement in relation to this group. METHOD: Semi-structured interviews obtained responses from seven carers. Transcripts were examined using interpretative phenomenological analysis. RESULTS: Two superordinate themes emerged: 'difficulty articulating the experience of loss' and 'making sense of bereavement through familiar patterns'. CONCLUSIONS: Carers conceptualize bereavement primarily in cognitive terms, but also take account of relational factors mediating loss. Implications for training and further research are outlined. PMID- 27554863 TI - Paleodysmorphology and paleoteratology: Diagnosing and interpreting congenital conditions of the skeleton in anthropological contexts. AB - Most congenital conditions have low prevalence, but collectively they occur in a few percent of all live births. Congenital conditions are rarely encountered in anthropological studies, not least because many of them have no obvious effect on the skeleton. Here, we discuss two groups of congenital conditions that specifically affect the skeleton, either qualitatively or quantitatively. Skeletal dysplasias (osteochondrodysplasias) interfere with the histological formation, growth and maturation of skeletal tissues leading to diminished postural length, but the building plan of the body is unaffected. Well- known skeletal dysplasias represented in the archeological record include osteogenesis imperfecta and achondroplasia. Dysostoses, in contrast, interfere with the building plan of the body, leading to e.g. missing or extraskeletal elements, but the histology of the skeletal tissues is unaffected. Dysostoses can concern the extremities (e.g., oligodactyly and polydactyly), the vertebral column (e.g., homeotic and meristic anomalies), or the craniofacial region. Conditions pertaining to the cranial sutures, i.e., craniosynostoses, can be either skeletal dysplasias or dysostoses. Congenital conditions that are not harmful to the individual are known as anatomical variations, several of which have a high and population-specific prevalence that could potentially make them useful for determining ethnic origins. In individual cases, specific congenital conditions could be determinative in establishing identity, provided that ante-mortem registration of those conditions was ensured. Clin. Anat. 29:878-891, 2016. (c) 2016 The Authors Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists. PMID- 27554865 TI - The psychometric properties of the Ages & Stages Questionnaires for ages 2-2.5: a systematic review. AB - BACKGROUND: Early identification of children with potential development delay is essential to ensure access to care. The Ages & Stages Questionnaires (ASQ) is used as population outcome indicators in England as part of the 2.5-year review. METHOD: The aim of this article was to systematically review the worldwide evidence for the psychometric properties of the ASQ third edition (ASQ-3TM ) and the Ages & Stages Questionnaires(r): Social-Emotional (ASQ:SE). Eight electronic databases and grey literature were searched for original research studies available in English language, which reported reliability, validity or responsiveness of the ASQ-3TM or ASQ:SE for children aged between 2 and 2.5 years. Twenty studies were included. Eligible studies used either the ASQ-3TM or the ASQ:SE and reported at least one measurement property of the ASQ-3TM and/or ASQ:SE. Data were extracted from all papers identified for final inclusion, drawing on Cochrane guidelines. RESULTS: Using 'positive', 'intermediate' and 'negative' criteria for evaluating psychometric properties, results showed 'positive' reliability values in 11/18 instances reported, 'positive' sensitivity values in 13/18 instances reported and 'positive' specificity values in 19/19 instances reported. CONCLUSIONS: Variations in age or language versions used, quality of psychometric properties and quality of papers resulted in heterogeneous evidence. It is important to consider differences in cultural and contextual factors when measuring child development using these indicators. Further research is very likely to have an important impact on the interpretation of the ASQ-3TM and ASQ:SE psychometric evidence. PMID- 27554864 TI - Nuclear Perilipin 5 integrates lipid droplet lipolysis with PGC-1alpha/SIRT1 dependent transcriptional regulation of mitochondrial function. AB - Dysfunctional cellular lipid metabolism contributes to common chronic human diseases, including type 2 diabetes, obesity, fatty liver disease and diabetic cardiomyopathy. How cells balance lipid storage and mitochondrial oxidative capacity is poorly understood. Here we identify the lipid droplet protein Perilipin 5 as a catecholamine-triggered interaction partner of PGC-1alpha. We report that during catecholamine-stimulated lipolysis, Perilipin 5 is phosphorylated by protein kinase A and forms transcriptional complexes with PGC 1alpha and SIRT1 in the nucleus. Perilipin 5 promotes PGC-1alpha co-activator function by disinhibiting SIRT1 deacetylase activity. We show by gain-and-loss of function studies in cells that nuclear Perilipin 5 promotes transcription of genes that mediate mitochondrial biogenesis and oxidative function. We propose that Perilipin 5 is an important molecular link that couples the coordinated catecholamine activation of the PKA pathway and of lipid droplet lipolysis with transcriptional regulation to promote efficient fatty acid catabolism and prevent mitochondrial dysfunction. PMID- 27554866 TI - Anti-Candida activity of geraniol involves disruption of cell membrane integrity and function. AB - Candidiasis is a major problem in immunocompromised patients. Candida, an opportunistic fungal pathogen, is a major health concern today as conventional drugs are highly toxic with undesirable side effects. Their fungistatic nature is responsible for drug resistance in continuously evolving strains. Geraniol, an acyclic monoterpene alcohol, is a component of several plant essential oils. In the present study, an attempt has been made to understand the antifungal activity of geraniol at the cell membrane level in three Candida species. With an MIC of 30-130MUg/mL, this natural compound was fungicidal at concentrations 2*MIC. There was complete suppression of fungal growth at MIC values (growth curves) and encouragingly geraniol is non-toxic even at the concentrations approaching 5*MIC (hemolysis assay). Exposed cells showed altered morphology, wherein the cells appeared either broken or shrivelled up (SEM studies). Significant reduction was seen in ergosterol levels at sub-MIC and glucose-induced H(+) efflux at concentrations>MIC values. Our results suggest that geraniol disrupts cell membrane integrity by interfering with ergosterol biosynthesis and inhibiting the very crucial PM-ATPase. It may hence be used in the management and treatment of both superficial and invasive candidiasis but further studies are required to elaborate its mode of action. PMID- 27554867 TI - [Evolution of tinea capitis observed in mycology laboratory of institute Pasteur of Algeria from1995 to 2015]. AB - : Tinea capitis are common in Algeria and are a frequent reason for consultation. This mycosis affects children and rarely adults. This is a retrospective study over a period of 20 years from 1995 to 2015 at the mycology laboratory of the Pasteur institute of Algeria. OBJECTIVE OF THE STUDY: Observe the evolution of these tinea over the years, to study the epidemiological aspects and identify the responsible agents. PATIENTS: This study concerned patients of all ages and sexes living in the region of Algiers and the environs, consultant for various scalp lesions. MATERIALS AND METHODS: For each patient, a completed information sheet is developed in insisting on the presence of animals and people with similar lesions. For each sampling, direct examination and culture on Sabouraud medium and antibiotics are utilized. The cultures are put at T degrees 27 to 28 degrees C and controlled regularly during 3 to 4 weeks. RESULTS: A total of 2664 samples were collected, 892 examinations were positive corresponding to a frequency of 33.48%. The age group 0-10 years is the most affected 710 cases (79.60%), with a slight predominance for male sex 502 cases (56.27%) and 390 cases (43.72%) for female sex. Eight hundred and fifty-five dermatophytes strains were isolated. Among the species found, Trichophyton violaceum is the most species isolated (59.41%), followed by Microsporum canis to 35.08%. In our series, the number of cases of tinea has increased slightly over the years, the rate of 26% in 2001 has progressed to 41.02% in 2015. From 1995 to 2011, T. violaceum was the predominant species, but from the year 2011 we see an increase of M. canis and decreased of T. violaceum. CONCLUSION: Tinea capitis remains frequent in Algeria and affects preferentially the children. T. violaceum and M. canis dominate the dermatophytic flora. Tinea trichophytic anthropophiles have progressively decreased in favor of tinea microsporic zoophiles who saw their number increased. PMID- 27554868 TI - Optimization of antifungal activity of Aeollanthus heliotropioides oliv essential oil and Time Kill Kinetic Assay. AB - OBJECTIVE: The limitations encountered in the management of fungal infections are due to the resistance, high toxicity, and overuse of conventional antifungal drugs. For bringing solutions, the antifungal activity of Aeollanthus heliotropioides essential oil will be evaluated and optimized. MATERIAL AND METHODS: The aerial parts of A. heliotropioides were harvested and essential oil extracted by hydrodistillation. The chemical composition was determined using gas chromatography and gas chromatography coupled with mass spectrometry and nuclear magnetic resonance. The sensitivity of fungal strains was determined using broth microdilution method. The fungicidal parameters were checked by viability assay using methylene blue dye. The Fractional Inhibitory Concentration Index was determined according the two-dimensional checkboard methods. The efficiency of the simulated optimum concentrations confirmed experimentally on American type culture collection strains, through the Time Kill Kinetic Study. RESULTS: The yield of extraction of essential oil was 0.1%. The major compounds were linalool (38.5%), Z-alpha-farnesene (25.1%), 9-hexa-decen-1-ol (13.9%) saturated/unsaturated massoia and gamma-lactones (4.5%). The MIC of extract on yeast isolates ranged from 0.6mg/mL to 5mg/mL. The combination of essential oil with thymol leads mainly to synergistic effects (0.5<=FICI). The optimums of essential oil (1.6+/-0.4MUl/mL) and thymol (0.6+/-0.1mg/mL) revealed a total inhibition of yeast after 120 and 180minutes according to the yeasts strains used. CONCLUSION: This study highlights the in vitro antifungal activity of A. heliotropioides essential oil and it synergistic effect with thymol. PMID- 27554869 TI - [Etiology of intertrigo in adults: A prospective study of 103 cases]. AB - INTRODUCTION: The etiologies of intertrigo in adults are numerous and different. The objective of our work was to study the epidemiological, clinical and the risk factors of intertrigo in adults. METHODS: We conducted a prospective study for a period of seven months in two Dermatology Units in Dakar (Senegal). All adults patient with intertrigo seen during this period who gave consent were included. RESULTS: One hundred and three patients with intertrigo were diagnosed with a hospital prevalence of 2.54%. The sex -ratio was 0.63 and the average age was 41. The study of habits and lifestyles of the patients found a history of intensive skin lightening, sport, wearing synthetic clothes and smoking in 26, 22, 20 and 22 cases, respectively. Infectious complications mainly bacterial (3.88%) and viral (1.94%) were reported in nine cases (8.7%). A dry erythroderma was noted in 3 cases (2.9%). It was found that the intertigo was commonly caused by fungal infections with a prevalence of 48.5% followed by immuno-allergic reactions with a prevalence of 34.9%, suppurative hidradenitis and inverse psoriasis with the same prevalence of 2.9%. Fifty-eight percent of cases with tinea and 63% of cases with candidiasis were women. Thirty-five percent of tinea cases and 45% of candidiasis cases were found to have a history of intensive skin lightening. CONCLUSION: The cause of intertrigo in adults are mainly infectious, particularly fungi, infections and immuno-allergic diseases. There are predisposing factors and some professions are more at risk. PMID- 27554913 TI - Re: Implementation of hospital-wide reform at improving access and flow: Impact on time to antibiotics in the emergency department. PMID- 27554914 TI - OBSERVING TODDLERS' INDIVIDUAL EXPERIENCES IN CLASSROOMS: INITIAL USE OF THE PARENTING INTERACTIONS WITH CHILDREN: CHECKLIST OF OBSERVATIONS LINKED TO OUTCOMES. AB - This study investigated using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO; Roggman, Cook, Innocenti, Norman, & Christiansen, 2013a) measure to assess teacher-child interactions experienced by individual toddlers within their childcare classrooms. Forty toddlers were observed, each during three 10-min cycles, and all their interactions with adults in the classroom were coded using the PICCOLO. Results, in terms of psychometric properties, indicate promise for using this measure to observe toddlers' individual experiences of teacher-child interactions in group settings. Furthermore, certain individual teacher-toddler interactions were associated with toddlers' problem behavior. Implications for use of the PICCOLO in early childhood classroom research and particular findings related to toddlers' behavior are discussed. PMID- 27554915 TI - Cloud Based Surveys to Assess Patient Perceptions of Health Care: 1000 Respondents in 3 days for US $300. AB - BACKGROUND: There are many challenges in conducting surveys of study participants, including cost, time, and ability to obtain quality and reproducible work. Cloudsourcing (an arrangement where a cloud provider is paid to carry out services that could be provided in-house) has the potential to provide vastly larger, less expensive, and more generalizable survey pools. OBJECTIVE: The objective of this study is to evaluate, using Amazon's Mechanical Turk (MTurk), a cloud-based workforce to assess patients' perspectives of health care. METHODS: A national online survey posted to Amazon's MTurk consisted of 33 multiple choice and open-ended questions. Continuous attributes were compared using t tests. RESULTS: We obtained 1084 responses for a total cost of US $298.10 in less than 3 days with 300 responses in under 6 hours. Of those, 44.74% (485/1084) were male and 54.80% (594/1084) female, representing 49 out of 50 states and aged 18 to 69 years. CONCLUSIONS: Amazon's MTurk is a potentially useful survey method for attaining information regarding public opinions and/or knowledge with the distinct advantage of cost, speed, and a wide and relatively good representation of the general population, in a confidential setting for respondents. PMID- 27554912 TI - Review article: the pathogenesis of pouchitis. AB - BACKGROUND: A total proctocolectomy followed by ileal pouch-anal anastomosis is a potentially curative surgery for ulcerative colitis or familial adenomatous polyposis. About 5-35% of patients with ulcerative colitis and 0-11% of patients with familial adenomatous polyposis develop subsequent inflammation of the ileal pouch termed pouchitis. AIM: To provide a comprehensive analysis of the research studying the possible pathogenesis of pouchitis. The goals were to identify promising areas of investigation, to help focus clinicians, researchers and patients on how to better understand and then potentially manage ileal pouchitis, and to provide avenues for future research investigations. METHODS: This review examined manuscripts from 1981 to 2015 that discussed and/or proposed hypotheses with supportive evidence for the potential underlying pathogenic mechanism for pouchitis. RESULTS: The pathogenesis of pouchitis is not definitively understood, but various hypotheses have been proposed, including (i) recurrence of ulcerative colitis, (ii) dysbiosis of the ileal pouch microbiota, (iii) deprivation of nutritional short-chain fatty acids, (iv) mucosal ischaemia and oxygen-free radical injury, (v) host genetic susceptibility and (vi) immune dysregulation. However, none of these alone are able to fully explain pouchitis pathogenesis. CONCLUSIONS: Pouchitis, similar to inflammatory bowel disease, is a complex disorder that is not caused by any one single factor. More likely, pouchitis occurs through a combination of both dysregulated host inflammatory mechanisms and interaction with luminal microbiota. PMID- 27554916 TI - A simple, reliable method for high-throughput screening for diabetes drugs using 3D beta-cell spheroids. AB - Early screens for new diabetes drugs rely on monolayers of beta-cells, which are known to be poor predictors of the in vivo response. Previously, we developed a method to create uniform islet spheroids from freshly-dispersed human donor tissue for drug screening. While the human engineered islets worked well to reduce donor-to-donor variability, it is difficult and expensive to obtain sufficient high-quality human islets for drug testing. Thus, this study utilized a genetically-modified beta-cell culture line (INS-1832/13) in 2D and as 3D spheroids and compared the results to human islet tissue formed into spheroids using a high-throughput 384-well format. In response to increasing concentrations of glucose, all 3 groups increased insulin release, but the cultured beta-cells (2D and 3D) were more sensitive to glucose (EC50 5.85mM for 2D beta-cells, 16.24mM for 3D beta-cell spheroids) than the human islet spheroids (EC50 53.69mM). The order of responses to glybenclamide was human spheroids >3D beta cell culture >2D beta-cell culture. In response to caffeine, the beta-cells in 2D or 3D were more responsive compared to the human islet spheroids (EC50 0.39 and 0.31mM for 2D and 3D beta-cells respectively). When exposed to inhibitors of insulin secretion (nifedipine and diazoxide), the responses were more similar between groups. Z' calculations, indicative of assay quality, determined that the 3D beta-cell spheroids reached the criteria of an excellent to ideal drug screen assay more consistently than the other test models. In conclusion, 3D beta-cell spheroids from a cultured cell line can be used in HTS assays that, according to reference drugs tested here, are sensitive and predictive of the in vivo response. PMID- 27554917 TI - A standardized approach for the assessment and treatment of internationally adopted children with a previously repaired anorectal malformation (ARM). AB - INTRODUCTION: A significant number of internationally adopted children have congenital birth defects. As a specialist center for colorectal diagnoses, we evaluate such children with an anorectal malformation (ARM) and have found that a significant number need a reoperation. Knowledge of the common complications following ARM surgery has led us to develop treatment algorithms for patients with unknown past medical and surgical history, a situation typically encountered in the adopted population. METHODS: The results of investigations, indications, and rate of reoperation were assessed for adopted children with an ARM evaluated between 2014 and 2016. RESULTS: 56 patients (28 males) were identified. 76.8% required reoperative surgery. Mislocation of the anus outside the sphincter complex was seen in 50% of males and 39.3% of females. Anal stricture, rectal prolapse, retained vaginal septum, and a strictured vaginal introitus were also common. CONCLUSION: The reoperative surgery rate in the internationally adopted child with an ARM is high. Complete, systematic evaluation of these children is required to identify complications following initial repair. Development of mechanisms to improve the primary surgical care these children receive is needed. PMID- 27554918 TI - Membrane Glycolipids Content Variety in Gastrointestinal Tumors and Transplantable Hepatomas in Mice. AB - BACKGROUND The aim of this study was to investigate the variety of plasma contents of membrane glycolipids in 65 gastrointestinal tumors and 31 transplant hepatomas in mice. MATERIAL AND METHODS The experimental model was a transplantable murine hepatoma. Experimental mice were divided into 3 groups. RESULTS The LSA and TSA content in the 2 groups were significantly difference (p<0.01), and were significantly lower in the therapeutic group than in the control group (p<0.01). CONCLUSIONS These results indicate that membrane glycolipids index LSA and TSA are sensitive markers in gastrointestinal tumors. In the transplanted hepatomas in mice, they may be considered as ancillary indicators for judging the therapeutic effect of hepatoma. PMID- 27554919 TI - Limits to sustained energy intake XXV: milk energy output and thermogenesis in Swiss mice lactating at thermoneutrality. AB - Previous studies at 21 degrees C and 5 degrees C suggest that in Swiss mice sustained energy intake (SusEI) and reproductive performance are constrained by the mammary capacity to produce milk. We aimed to establish if this constraint also applied at higher ambient temperature (30 degrees C). Female Swiss mice lactating at 30 degrees C had lower asymptotic food intake and weaned lighter litters than those at 21 degrees C. Resting metabolic rate, daily energy expenditure, milk energy output and suckling time were all lower at 30 degrees C. In a second experiment we gave mice at 30 degrees C either 6 or 9 pups to raise. Female performance was independent of litter size, indicating that it is probably not controlled by pup demands. In a third experiment we exposed only the mother, or only the offspring to the elevated temperature. In this case the performance of the mother was only reduced when she was exposed, and not when her pups were exposed, showing that the high temperature directly constrains female performance. These data suggest that at 30 degrees C SusEI and reproductive performance are likely constrained by the capacity of females to dissipate body heat, and not indirectly via pup demands. Constraints seem to change with ambient temperature in this strain of mouse. PMID- 27554920 TI - Successful treatment of limy bile syndrome extending to the common bile duct by laparoscopic cholecystectomy and common bile duct exploration: A case report and literature review. AB - Limy bile syndrome extending to the common bile duct (CBD) is a rare condition that lacks a standardized treatment. Laparoscopic cholecystectomy with laparoscopic choledocholithotomy by CBD exploration is preferred because it preserves the function of the sphincter of the Vater's papilla and allows treatment of both lesions. A 37-year-old man who was receiving entecavir for chronic hepatitis B developed right upper quadrant pain. Abdominal ultrasonography revealed a calcified shadow in the gallbladder and CBD. Abdominal imaging revealed a liquid-like material identified by a calcified shadow in two phases separated by a fluid-fluid level. Abdominal and 3-D drip infusion cholangiography CT showed stones in the gallbladder and CBD with limy bile. The patient underwent laparoscopic cholecystectomy and choledocholithotomy. Intraoperatively, white-yellow-colored bile and stones were drained from the CBD. A C-tube was placed. Postoperatively, remnant stones and radiopaque materials were absent. The stones comprised of >95% calcium carbonate. PMID- 27554921 TI - Effect of MRJF4 on C6 Glioma Cells Proliferation and Migration. AB - BACKGROUND: MRJF4, a novel haloperidol metabolite II prodrug, was obtained through the esterification of the secondary hydroxyl group of haloperidol metabolite II with 4-phenylbutyric acid. The activities of (+/-)-MRJF4 and its two enantiomers [(+)-MRJF4 and (-)-MRJF4] as tumor specific inducers of pro apoptotic genes were evaluated on malignant C6 glioma cells. In particular, changes in Nf-kappaB signaling pathway, activity of nitric oxide synthases (NOS), metalloproteinases (MMPs), and membrane adhesion proteins were investigated. RESULTS: IkappaBalpha reduced phosphorylation and iNOS lowered activity could be correlated with the previously demonstrated decreased proliferation and tumor progression of C6 cells upon 24 h of treatment with all the three compounds. Integrin beta1 decreased expression, at the same experimental time, seems to support lower C6 cells migrative capability and the consequent reduced invasiveness of these cells upon treatment with (+/-)-MRJF4 and its enantiomers. CONCLUSION: These results suggest that this multi-target prodrug and its two enantiomers might be a valuable clinical tool for the treatment of metastatic glioblastoma. PMID- 27554922 TI - Anticancer, Antioxidant and Cytotoxic Potential of Thymol in vitro Brain Tumor Cell Model. AB - BACKGROUND: Thymol (THY), which is a monocyclic monoterpene, found in oil of thyme various other kinds of plants. Until today, although different biological properties of THY have been indicated, its neurological toxicity has never been investigated. METHOD: In this study, in vitro antiproliferative (by 3-(4,5 dimetylthiazol-2-yl)-2,5 diphenlytetrazolium bromide (MTT) test), genotoxic (by single cell gel electrophoresis (SCGE)) and oxidative effects (by total antioxidant capacity (TAC) and total oxidative status (TOS) analysis) of THY (0 400 mg/L) were assessed on cultured primary rat neurons (CPRNs) and N2a neuroblastoma cells. RESULTS: The obtained data from MTT analysis revealed that THY (only at 400 mg/L) led to significant (p<0.05) decreases of the cell viability in cultured primary rat neurons. And, THY was found to inhibit cell growth in N2a cells at concentrations of 200 and 400 mg/L. Again, DNA damage rates were statistically indifferent (p>0.05) in both treated cell type as compared to control group. The present results also showed that 10, 25 and 50 mg/L of THY application into the cell cultures supported antioxidant capacity in primary rat neurons but not in N2a cells. CONCLUSION: In a conclusion, these results confirm that THY may have antiproliferative potential against brain tumor cells involving oxidative alteration. PMID- 27554923 TI - High chronic training loads and exposure to bouts of maximal velocity running reduce injury risk in elite Gaelic football. AB - OBJECTIVES: To examine the relationship between chronic training loads, number of exposures to maximal velocity, the distance covered at maximal velocity, percentage of maximal velocity in training and match-play and subsequent injury risk in elite Gaelic footballers. DESIGN: Prospective cohort design. METHODS: Thirty-seven elite Gaelic footballers from one elite squad were involved in a one season study. Training and game loads (session-RPE multiplied by duration in min) were recorded in conjunction with external match and training loads (using global positioning system technology) to measure the distance covered at maximal velocity, relative maximal velocity and the number of player exposures to maximal velocity across weekly periods during the season. Lower limb injuries were also recorded. Training load and GPS data were modelled against injury data using logistic regression. Odds ratios (OR) were calculated based on chronic training load status, relative maximal velocity and number of exposures to maximal velocity with these reported against the lowest reference group for these variables. RESULTS: Players who produced over 95% maximal velocity on at least one occasion within training environments had lower risk of injury compared to the reference group of 85% maximal velocity on at least one occasion (OR: 0.12, p=0.001). Higher chronic training loads (>=4750AU) allowed players to tolerate increased distances (between 90 to 120m) and exposures to maximal velocity (between 10 to 15 exposures), with these exposures having a protective effect compared to lower exposures (OR: 0.22 p=0.026) and distance (OR=0.23, p=0.055). CONCLUSIONS: Players who had higher chronic training loads (>=4750AU) tolerated increased distances and exposures to maximal velocity when compared to players exposed to low chronic training loads (<=4750AU). Under- and over-exposure of players to maximal velocity events (represented by a U-shaped curve) increased the risk of injury. PMID- 27554924 TI - The effects of dose and diet on the pharmacodynamics of omeprazole in the horse. AB - BACKGROUND: Conflicting data are presented in the current literature regarding the efficacy of omeprazole for suppressing gastric acidity in the horse. OBJECTIVES: The objective of this study was to investigate the duration of intraday acid suppression achieved with two doses of omeprazole under two different dietary conditions. STUDY DESIGN: A four-way crossover design. METHODS: Six adult Thoroughbred horses instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00-07.00 h) for six consecutive days (Days 0-5). Baseline data was recorded on Day 0 and omeprazole administered on Days 1-5. Two doses (1 mg/kg and 4 mg/kg bwt per os once a day) and two diets (a high grain/low fibre [HG/LF] and ad libitum hay [HAY)] diet) were studied. Data for the percent (%) time pH was above 4 (%tpH>4) and median intraday pH was reported for two measurement locations and analysed using generalised estimating equations. RESULTS: An effect of both diet and dose was evident with mean %tpH>4 and the mean of the median intraday pHs typically higher at the higher (4 mg/kg bwt) dose and in HG/LF diet. The overall efficacy of omeprazole in raising intragastric pH was good under the HG/LF conditions but relatively poor in the HAY diet. A cumulative effect of dosing, not previously reported in the horse, was observed. CONCLUSIONS: The overall efficacy of omeprazole in raising ventral gastric pH was less than previously reported. Both dose and diet may play a role in the efficacy of omeprazole in the horse. Therefore, the use of singular dosing recommendations that encompass all horse types and management conditions may not be appropriate and dosing recommendations that take into account the diet of the horse may be advantageous. PMID- 27554925 TI - Prognostic factors in traumatic atlanto-occipital dislocation. AB - Traumatic atlanto-occipital dislocation (AOD) is an ominous injury with high mortality and morbidity in trauma patients. Improved survival has been observed with advancements in pre-hospital and hospital care. Furthermore, high quality imaging studies are accessible at most trauma centers; these are crucial for prompt diagnosis of AOD. The objective of this study is to perform a comprehensive literature review of traumatic AOD, with specific emphasis on identifying prognostic factors for survival. A review of the literature was performed using the Medline database for all traumatic atlanto-occipital articles published between March 1959 and June 2015; 141 patients from 60 total studies met eligibility criteria for study inclusion. A binary logistic regression model was utilized to identify prognostic factors. The analysis assessed age, sex, spinal cord injury (SCI), traumatic brain injury (TBI), polytrauma injury (PI), and Traynelis AOD Classification. Only TBI was statistically significantly associated with death (OR 8.05 p<0.05); SCI did not reach statistical significance for predicting mortality in AOD patients (OR 1.25 p>0.05). Age, sex, PI, and Traynelis AOD Classification did not meet significance to predict mortality in AOD patients. We found that patients with TBI are eight times more likely to die than patients without TBI. A high degree of suspicion for AOD during pre-hospital care, as well as, prompt diagnosis and management in the trauma center play a key role in the treatment of this devastating injury. The relationship between survival and factors such as TBI and SCI should be further explored. PMID- 27554926 TI - Relationship between endometritis and oxidative stress in the follicular fluid and luteal function in the buffalo. AB - In this study, alteration in the follicular fluid composition and luteal function was investigated in the buffalo with endometritis. Genitalia were classified into cytological and purulent endometritis on the basis of polymorphonuclear cell cut off while non-endometritis served as control (n = 10/group). In the follicular phase, the number of surface follicles was counted, diameter of the largest follicle was measured and the follicular fluid was assayed for total protein, cholesterol, malondialdehyde (MDA), total antioxidant capacity (TAC), oestradiol (E2 ) and progesterone (P4 ). The P4 content of corpus luteum during mid-luteal phase was estimated by radioimmunoassay. Ovaries from the follicular phase of oestrous cycle showed no significant difference in the total number of surface follicles, size of the largest follicle and volume of follicular fluid in the buffaloes with and without endometritis (p > .05). However, the antral fluid of the largest follicle from the genitalia of buffalo with cytological and purulent endometritis showed a significant decrease in the concentration of total protein, cholesterol, TAC and E2 and a significant increase in the concentration of MDA and P4 (p < .05). The results indicated that there is an association between endometritis and decreased ovarian function. PMID- 27554927 TI - Insights into molecular and cellular mechanisms of hormonal actions on fish ion regulation derived from the zebrafish model. AB - Fish have sophisticated mechanisms of ionic and acid-base regulation for maintaining body fluid homeostasis. Many hormones have been proposed to control the ionic and acid-base regulation mechanisms in fishes; however, lots of the proposed actions lack convincing cellular/molecular evidence. With the advantages of available genetic databases and molecular manipulation techniques, zebrafish has become an emerging model for research into ion transport physiology and functional regulation. Different types of ionocytes were found to transport ions through various sets of ion transporters, and the molecular mechanisms of ionocyte proliferation and differentiation have also been dissected, providing a competent platform with which to precisely study the ion transport pathways and ionocytes targeted by hormones, including isotocin, prolactin, cortisol, stanniocalcin-1, calcitonin, endothelin-1, vitamin D, parathyroid hormone 1, catecholamines, the renin-angiotensin-system, estrogen-related receptor alpha, and calcitonin gene-related peptide, which have been demonstrated to positively or negatively regulate ion transport through specific receptors at different molecular levels (transcriptional, translational, or posttranslational) or at different developmental stages of ionocytes (proliferation or differentiation). The knowledge obtained in zebrafish not only enhances our understanding of the hormonal control of fish ion regulation, but also informs studies on other animal species, thereby providing insights into related fields. PMID- 27554928 TI - Identification and characterization of a progestin and adipoQ receptor (PAQR) structurally related to Paqr7 in the ovary of Cynoglossus semilaevis and its potential role in regulating oocyte maturation. AB - Membrane progestin receptors (mPRs) play an important role in the regulation of oocyte meiotic maturation in fish. However, details of the molecular endocrine mechanism regulating oocyte maturation in multiple spawning fish with asynchronous ovarian development remain unclear. The cDNA encoding a novel progestin and adipoQ receptor with structural similarity to mPRalpha (Paqr7), herein called Paqr7b, was cloned and sequenced from the ovary of half-smooth tongue sole Cynoglossus semilaevis. Phylogenetic analysis showed that Paqr7b represents an evolutionary intermediate between mPRalpha and mPRbeta and shares high homology with other similar Paqr proteins in other teleost species. However, the tongue sole Paqr7b protein showed much greater homology to teleost mPRalphas (average 52%) than mPRbetas (average 40%), suggesting it may have arisen from gene duplication of mPRalpha. paqr7b and paqr7 mRNA exhibited similar patterns of tissue expression. The mRNA and protein of Paqr7b were ubiquitously detected in all tissues analyzed, including the ovary. Moreover, in situ hybridization results revealed that paqr7b was expressed in stage V oocytes, as well as in scattered cells in the pituitary. The expression of paqr7b mRNA in brain and ovary significantly increased from ovarian development stage II to stage V (P<0.05), and was maximal at stage V, and then sharply decreased at stage VI. The transcript level of paqr7b mRNA in the pituitary also peaked at stage V (P<0.05). Treatment of tongue sole ovarian follicles with gonadotropin consistently increased the expression level of Paqr7b protein and mRNA in both a dose- and stage-dependent manner. Microinjection of tongue sole oocytes with a morpholino antisense oligonucleotide to Paqr7b blocked the progestin induction of oocyte maturation. Our findings demonstrate an important role of Paqr7b in the regulation of oocyte maturation in tongue sole and suggest the receptor may also influence other aspects of reproduction, such as pituitary function. PMID- 27554929 TI - [Erratum to: Dexmedetomidine in the treatment of acute alcohol withdrawal delirium]. PMID- 27554930 TI - Magnetic-flux-driven topological quantum phase transition and manipulation of perfect edge states in graphene tube. AB - We study the tight-binding model for a graphene tube with perimeter N threaded by a magnetic field. We show exactly that this model has different nontrivial topological phases as the flux changes. The winding number, as an indicator of topological quantum phase transition (QPT) fixes at N/3 if N/3 equals to its integer part [N/3], otherwise it jumps between [N/3] and [N/3] + 1 periodically as the flux varies a flux quantum. For an open tube with zigzag boundary condition, exact edge states are obtained. There exist two perfect midgap edge states, in which the particle is completely located at the boundary, even for a tube with finite length. The threading flux can be employed to control the quantum states: transferring the perfect edge state from one end to the other, or generating maximal entanglement between them. PMID- 27554931 TI - Better research is needed on surgery for lumbar spinal stenosis. PMID- 27554932 TI - Spectroscopic studies on the interaction of DNA with the copper complexes of NSAIDs lornoxicam and isoxicam. AB - Non Steroidal Anti-inflammatory Drugs (NSAIDs) form the most common class of anti inflammatory and analgesic agents. They also show anticancer properties for which they exert their effects by interacting at the protein but not at the genomic level. This is because most NSAIDs are anions at physiological pH, which prohibit their approach to the polyanionic DNA backbone. Complexing NSAIDs with bioactive metal like copper obliterates this disadvantage. Here, copper complexes of two oxicam NSAIDs, Lornoxicam (Lx) and Isoxicam (Isx) have been chosen to study their interaction with calf thymus (ct) DNA and have been synthesized as per reported protocols. UV-vis absorption showed that DNA binding to Cu(II)-Lx complex alters the absorption spectra indicating changes in the electronic environment of the complex, whereas, for Cu(II)-Isx there was only small changes. Hence, UV-vis absorption was used to determine the binding constant, stoichiometry and thermodynamic parameters of Cu(II)-Lx. However, UV-melting studies and CD difference spectra showed that both Cu(II)-Lx and Cu(II)-Isx can interact with the DNA backbone albeit with different binding modes. The probable binding mode was determined by kinetics of EtBr displacement and viscosity measurements. Our results point to an intercalative mode of binding for Cu(II)-Lx and external groove binding for Cu(II)-Isx. PMID- 27554933 TI - Structure and digestion of hybrid Indica rice starch and its biosynthesis. AB - The fine structure (including contents, size and chains length distribution) of amylose and amylopectin of Hybrid Indica Rice starch have an impact on digestion properties of Indica Rice. Indica Rice starches with different amylose contents were chosen as model materials in this study. The amylose and amylopectin size were characterized using size-exclusion chromatography (SEC), the fine structure of amylopectin were studied by flurophore-assisted carbohydrate electrophoresis (FACE) and parameterized by amylopectin biosynthesis model to identify associations with starch digestibility. The digestograms of all starches fit first-order kinetics. All results show that the hybrid Indica rice starch with higher amylose content has a slower digestion rate. SEC results show that there is no obviously in chains length distribution (CLD) for amylopectin, but a significantly sharp difference in amylose. No difference in amylopectin was also observed from FACE result. The amylose starch controlled by GBSSI enzyme may be the key parameter to influence starch digestion. PMID- 27554935 TI - Extraction, characterization, and biological activity of polysaccharides from Sophora flavescens Ait. AB - Four water-soluble polysaccharides, designated as SF1, SF2, SF3 and SF4, were efficiently extracted from the roots of Sophora flavescens by mechanochemistry under the conditions of rotational speed of 400rpm, grinding time of 10min, powder to ball weight ratio of 1:20, and Na2CO3 loading of 7wt%. The results obtained indicated that all of these four acid heteropolysaccharides are composed of rhamnose, arabinose, xylose, mannose, glucose and galactose, with the average molecular weights of 400.9, 98.6, 99.3, 42.7kDa, respectively. In vitro, SF4 showed the most significant scavenging activity on superoxide radical, ABTS, and DPPH radical, while SF3 had the most significant scavenging activity on hydroxyl radical. Immunological tests demonstrated that SF1, SF2, SF3 and SF4 significantly stimulated nitric oxide production without cytotoxicity in macrophages and promoted splenocyte proliferation. These data suggest that the four polysaccharides fractions have the potential as novel natural sources of antioxidative and immunopotentiating agents. PMID- 27554934 TI - Carboxylated graphene oxide functionalized with beta-cyclodextrin-Engineering of a novel nanohybrid drug carrier. AB - In this paper, we selected biocompatible carboxylated graphene oxide (GeneO-COOH) as a base material. The nanohybrid drug carriers composed of GeneO-COOH and cyclodextrin (beta-CD), have been successfully synthesized through esterification and self-assembly technique. The nanohybrid drug carriers of GeneO-COO-beta-CD were characterized by X-ray diffraction (XRD), fourier infrared spectroscopy (FTIR), thermogravimetric analysis (TG), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and solubility experiments. Results indicated that the nanohybrid was obtained with GeneO-COOH forming the core and a large number of beta-CD molecules forming the shell with a special structure. In the nanohybrid, the westerification between GeneO-COOH and beta-CD led to the formation of covalent bonds, while adjacent beta-CD molecules engineer an outer shell composed of 100 beta-CD molecules (ca. 800nm of thickness) in the form of a layer-by-layer self-assembly due to hydrogen-bonding interaction. The obtained novel nanohybrid drug carriers of GeneO-COO-beta-CD possessed good dispersibility in water media and the solutions were found to remain stable for 12 months,providing a possibility for further applications in biology, medicine, agriculture and other fields. PMID- 27554936 TI - Crosslinked quaternized chitosan/bentonite composite for the removal of Amino black 10B from aqueous solutions. AB - In this work, the crosslinked quaternized chitosan/bentonite composite was prepared by membrane-forming and cross-linking methods, and characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) techniques. Batch mode was adapted for the adsorption studies. The equilibrium data and kinetic data were well described by the Langmuir isotherm and the pseudo second-order kinetic model, respectively. There was not much drop in adsorption capacity up to 5th regeneration cycle. The maximum monolayer adsorption capacity was obtained at 990.1mg/g at 298K and natural pH in terms of the Langmuir model. The high adsorption capacity was attributed to the strong electrostatic interaction as well as the valence forces through the sharing or exchange of electrons between dye molecules and this composite. The thermodynamic parameters indicated the adsorption of Amino black 10B by this composite was a spontaneous and endothermic process. PMID- 27554937 TI - A novel anticoagulant protein with antithrombotic properties from the mosquito Culex pipiens pallens. AB - A newly discovered protein, named 'CPP protein', which possesses antithrombotic and anticoagulant properties, was purified from the salivary gland of the mosquito Culex pipiens pallens. CPP protein was found to have an estimated molecular mass of 21.7kDa, and to be active at 60 degrees C, and pH 7.0. The anticoagulation activity of CPP protein was strongly inhibited by calcium ions. CPP protein inhibited fibrin clot formation and platelet activation, and it degraded blood clots. It also inhibited the enzymatic activities of activated factor X and thrombin. In addition, CPP protein prolonged the activated partial thromboplastin time and prothrombin time. CPP protein demonstrated antithrombotic effect in two mouse models, a thrombin-induced acute thromboembolism model, and an ex vivo coagulation model. CPP protein at a dose of 20mg/kg was devoid of hemorrhagic activity. These results suggest that CPP protein could have potential as a therapeutic agent for thrombosis, due to its antithrombotic properties and lack of hemorrhagic activity. PMID- 27554938 TI - Engineering increased thermostability in the GH-10 endo-1,4-beta-xylanase from Thermoascus aurantiacus CBMAI 756. AB - The GH10 endo-xylanase from Thermoascus aurantiacus CBMAI 756 (XynA) is industrially attractive due to its considerable thermostability and high specific activity. Considering the possibility of a further improvement in thermostability, eleven mutants were created in the present study via site directed mutagenesis using XynA as a template. XynA and its mutants were successfully overexpressed in Escherichia coli Rosetta-gami DE3 and purified, exhibiting maximum xylanolytic activity at pH 5 and 65 degrees C. Three of the eleven mutants, Q158R, H209N, and N257D, demonstrated increased thermostability relative to the wild type at 70 degrees C and 75 degrees C.Q158R and N257D were stable in the pH range 5.0-10.0, while WT and H209N were stable from pH 8-10. CD analysis demonstrated that the WT and the three mutant enzymes were expressed in a folded form. H209N was the most thermostable mutant, showing a Tm of 71.3 degrees C. Molecular dynamics modeling analyses suggest that the increase in H209N thermostability may beattributed to a higher number of short helices and salt bridges, which displayed a positive charge in the catalytic core, stabilizing its tertiary structure. PMID- 27554939 TI - Mesenchymal stem cells growth and proliferation enhancement using PLA vs PCL based nanofibrous scaffolds. AB - Electrospinning of polymers is the most commonly used technique for nanofiber fabrication. polylactic acid (PLA) and polycaprolactone (PCL) have been shown to be ideal for nanofiber preparation in various biomedical applications, due to characteristics such as biodegradablity and their ability to promote the cell growth, similar to native tissues. The aim of this study was to develop biocompatible and biodegradable PLA and PCL-based nanofibrous scaffolds for enhancing stem cell growth and proliferation. The scaffolds were prepared by electrospinning, and their physicochemical properties were studied using Fourier Transform Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The surface morphology of the developed scaffolds was determined using scanning electron microscopy (SEM). Mesenchymal stem cells (MSCs), derived from both adipose tissue and bone marrow, were seeded onto the prepared nanofibrous scaffolds. The effect of scaffold type, and structural characteristics on survival and proliferation of MSCs were evaluated. Our results show that after full physicochemical characterization of PCL and PLA nanofibrous scaffolds both were safe and non toxic to the evaluated cells and both scaffolds supported cell attachment and proliferation of bone marrow and adipose tissue-derived MSCs. PMID- 27554940 TI - Measuring the efficacy of a project for adolescents and young adults with cancer: A study from the Milan Youth Project. AB - BACKGROUND: Various projects dedicated specifically to adolescents and young adults (AYA) with cancer have been developed in recent years. A critical aspect of such programs is the ability to demonstrate its value, and therefore how to measure desired outcomes. METHODS: A list of metrics to consider for demonstrating the advantages of an AYA program was identified and used to assess the activity of the Youth Project operating at the Pediatric Oncology Unit of the Istituto Nazionale Tumori in Milan. RESULTS: The number of newly diagnosed AYA patients seen at the Unit has increased since the formal launch of the Youth Project, from 65 to 81.2 cases/year. Concerning the 78 AYA patients presenting with malignant neoplasms in 2015, 82% were included in clinical trials (the other 18% in prospective observational studies). Fertility preservation measures were implemented for 59% of AYA patients considered at risk, and specific psychological support was provided in 70.6% of cases; 72.5% of patients actively participated in support activities. Other parameters considered were a preliminary satisfaction questionnaire administered to patients and the program's scientific recognition and acknowledgment by the community. CONCLUSIONS: The study proposed a number of potentially reproducible, practical parameters to consider in assessing the value of a program dedicated to AYA. These metrics were examined in terms of the activities of our Youth Project, and confirmed its efficacy. To be sustainable over time, AYA projects have to be accepted as a standard of care at the community and government levels. PMID- 27554941 TI - Echinococcus granulosus sensu stricto, Echinococcus canadensis (G7), and Echinococcus ortleppi in fertile hydatid cysts isolated from cattle in Southern Brazil. AB - Echinococcosis is a cosmopolitan zoonotic infection that affects humans and animals. The aim of this study was to identify and characterize the fertile hydatid cysts from bovine viscera in order to verify different species and/or genotypes present in Southern Brazil. Firstly, cysts were collected from a slaughterhouse, which received animals from different regions of Rio Grande do Sul State (RS), considered an important area of occurrence of cystic echinococcosis. In total, 2396 cysts were analyzed by microscopy to verify the presence of protoscoleces. Protoscoleces were detected in 291 samples and were classified as fertile hydatid cysts. Total DNA was extracted from protoscoleces and amplified by polymerase chain reaction (PCR). Two hundred and fifty-one samples were identified by PCR and characterized as G5/G6/G7 genotypes, of which 40 belonged to Echinococcus granulosus sensu stricto (G1-G3). PCR was also performed, using G5-specific primers to identify 250 samples as Echinococcus ortleppi (G5). Only one sample was identified as Echinococcus canadensis (G7) by DNA sequencing using primers specific for the coxI gene. Phylogenetic analysis was also performed and identified three distinct groups E1 (G5), E2 (G7), and E3 (G1-G3), which were grouped according to similarity of their sequences. The study highlights the fact that E. granulosus sensu stricto, E. ortleppi, and E. canadensis (G7) were infecting cattle in RS, emphasizing the adaptation of different species of Echinococcus to this intermediate host. PMID- 27554942 TI - A Cadaveric Study for the Improvement of Thread Carpal Tunnel Release. AB - PURPOSE: The thread carpal tunnel release (TCTR) technique has been improved and offers more precise control in dissecting thread placement. The purpose of this cadaveric study was to test the procedure operationally and verify the modified TCTR anatomically. METHODS: Eleven unembalmed cadaver wrists underwent the transverse carpal ligament (TCL) release by using the modified TCTR technique. An experienced observer dissected each specimen and assessed for completeness of release under direct visual assessment. Injury to the superficial palmar aponeurosis (SupPA), the Berrettini and common digital nerve branches were also recorded as a secondary outcome. RESULTS: Eleven out of 11 wrists (100%) underwent the modified TCTR with complete release of the TCL. All 11 wrists were released without damage to any vital neurovascular structure including the Berrettini branch and the common digital nerves. The SupPA remained intact in all 5 wrists performed with the preservation steps. CONCLUSIONS: The modified TCTR technique demonstrated complete division of the TCL while protecting the SupPA as well as the Berrettini and common digital nerve branches. CLINICAL RELEVANCE: The modified TCTR has the potential to offer a clinically safe and effective minimally invasive procedure for complete carpal tunnel release. PMID- 27554943 TI - Frequent interruptions of sedentary time modulates contraction- and insulin stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials. AB - Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID- 27554944 TI - Water ordering controls the dynamic equilibrium of micelle-fibre formation in self-assembly of peptide amphiphiles. AB - Understanding the role of water in governing the kinetics of the self-assembly processes of amphiphilic peptides remains elusive. Here, we use a multistage atomistic-coarse-grained approach, complemented by circular dichroism/infrared spectroscopy and dynamic light scattering experiments to highlight the dual nature of water in driving the self-assembly of peptide amphiphiles (PAs). We show computationally that water cage formation and breakage near the hydrophobic groups control the fusion dynamics and aggregation of PAs in the micellar stage. Simulations also suggest that enhanced structural ordering of vicinal water near the hydrophilic amino acids shifts the equilibrium towards the fibre phase and stimulates structure and order during the PA assembly into nanofibres. Experiments validate our simulation findings; the measured infrared O-H bond stretching frequency is reminiscent of an ice-like bond which suggests that the solvated water becomes increasingly ordered with time in the assembled peptide network, thus shedding light on the role of water in a self-assembly process. PMID- 27554945 TI - Continuous EEG monitoring enhances multimodal outcome prediction in hypoxic ischemic brain injury. AB - OBJECTIVE: Hypoxic brain injury is the largest contributor to disability and mortality after cardiac arrest. We aim to identify electroencephalogram (EEG) characteristics that can predict outcome on cardiac arrest patients treated with targeted temperature management (TTM). METHODS: We retrospectively examined clinical, EEG, functional outcome at discharge, and in-hospital mortality for 373 adult subjects with return of spontaneous circulation after cardiac arrest. Poor outcome was defined as a Cerebral Performance Category score of 3-5. Pure suppression-burst (SB) was defined as SB not associated with status epilepticus (SE), seizures, or generalized periodic discharges. RESULTS: In-hospital mortality was 68.6% (N=256). Presence of both unreactive EEG background and SE was associated with a positive predictive value (PPV) of 100% (95% confidence interval: 0.96-1) and a false-positive rate (FPR) of 0% (95% CI: 0-0.11) for poor functional outcome. A prediction model including demographics data, admission exam, presence of status epilepticus, pure SB, and lack of EEG reactivity had an area under the curve of 0.92 (95% CI: 0.87-0.95) for poor functional outcome prediction, and 0.96 (95% CI: 0.94-0.98) for in-hospital mortality. Presence of pure SB (N=87) was confounded by anesthetics use in 83.9% of the cases, and was not an independent predictor of poor functional outcome, having a FPR of 23% (95% CI: 0.19-0.28). CONCLUSIONS: An unreactive EEG background and SE predicted poor functional outcome and in-hospital mortality in cardiac arrest patients undergoing TTM. Prognostic value of pure SB is confounded by use of sedative agents, and its use on prognostication decisions should be made with caution. PMID- 27554946 TI - Conversion to shockable rhythms is associated with better outcomes in out-of hospital cardiac arrest patients with initial asystole but not in those with pulseless electrical activity. AB - BACKGROUND: The prognostic implication of conversion from initially non-shockable to shockable rhythms in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. Our objective is to determine whether the conversion to shockable rhythms is a reliable predictor of short- and long-term outcomes both in patients who initially presented with pulseless electrical activity (PEA) and in those with asystole. METHODS: A secondary analysis was performed on non traumatic OHCA cases >=18 years old with PEA or asystole as initial rhythms, who were treated in the field and enrolled in the Resuscitation Outcomes Consortium (ROC) PRIMED study (clinicaltrials.gov/ct2/show/NCT00394706). We reported the characteristics and outcomes for those patients with or without shocks delivered in the field. Logistic regression analysis assessed the association of shock delivery with pre-hospital return of spontaneous circulation (ROSC), survival to hospital discharge and favorable neurological outcome as well. RESULTS: Of the 9902 included cases, 3415 (34.5%) were initially in PEA and 6487 (65.5%) were in asystole. 744 (21.8%) PEA and 1134 (17.5%) asystolic patients underwent rhythm conversions and received subsequent shocks. For asystolic patients, the adjusted odds ratios (ORs) of shock delivery for pre-hospital ROSC, survival to discharge and favorable neurological outcome were 1.862 (95%CI 1.590-2.180), 3.778 (95%CI 2.374-6.014) and 4.154 (95%CI 2.192-7.871) respectively, while for PEA patients they were 0.951 (95%CI 0.796-1.137), 1.115 (95%CI 0.720-1.726) and 1.373 (95%CI 0.790-2.385) respectively. CONCLUSIONS: Conversion to shockable rhythms was associated with better outcomes in initially asystolic OHCA patients, whereas such associations were not observed in patients initially in PEA. PMID- 27554947 TI - Anticoagulation therapy in atrial fibrillation after intracranial hemorrhage. AB - BACKGROUND: The effect of oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF) with a history of intracranial hemorrhage (ICH) is poorly defined. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of OAT in patients with AF with an ICH history. METHODS: We retrospectively compared the composite end point, including thromboembolic and major bleeding events, between patients with AF with a history of ICH who were (OAT group, n = 254) and those who were not (no-OAT group, n = 174) taking OAT. RESULTS: During a mean follow-up of 39.5 +/- 31.9 months, 5.5 and 3.1 major bleeding events/100 patient-years were observed in the OAT and no-OAT groups, respectively (P = .024). Recurrent ICH was observed only in patient with OAT. Thromboembolic events occurred in 2.4 and 8.3 events/100 patient-years in OAT and no-OAT groups, respectively (P < .001). There was no significant differences in composite end points between OAT and no-OAT groups (11.5 events/100 patient-years vs 7.9 events/100 patient-years; P = .154). Patients with OAT who achieved a time in-therapeutic range of >=60% of the international normalized ratio of 2.0-3.0 demonstrated a better cumulative survival free of the composite end point (P < .001) than did patients without OAT. Early (<2 weeks) OAT after an index ICH did not improve composite end points because of the increased incidence of major bleeding events. However, OAT at 2 weeks after an index ICH was associated with decreased clinical events including thromboembolic events and composite end point. CONCLUSION: In patients with AF who require anticoagulation and have a history of ICH, maintaining optimal OAT with time-in-therapeutic range >= 60% and the initiation of OAT at least 2 weeks after an index ICH were associated with improved clinical outcomes. PMID- 27554948 TI - Flecainide versus digoxin for fetal supraventricular tachycardia: Comparison of two drug treatment protocols. AB - BACKGROUND: The optimal treatment for fetal supraventricular tachycardia (SVT) with 1:1 atrioventricular relationship is unclear. OBJECTIVE: We compared the effectiveness of transplacental treatment protocols used in 2 centers. METHODS: Pharmacologic treatment was used in 84 fetuses. Maternal oral flecainide was the primary therapy in center 1 (n = 34) and intravenous maternal digoxin in center 2 (n = 50). SVT mechanism was classified by mechanical ventriculoatrial (VA) time intervals as short VA or long VA. Treatment success was defined as conversion to sinus rhythm (SR), or rate control, defined as >15% rate reduction. RESULTS: Short VA interval occurred in 67 fetuses (80%) and long VA in 17 (20%). Hydrops was present 28 of 84 (33%). For short VA SVT, conversion to SR was 29 of 42 (69%) for digoxin and 24 of 25 (96%) for flecainide (P = .01). For long VA SVT, conversion to SR and rate control was 4 of 8 (50%) and 0 of 8, respectively, for digoxin, and 6 of 9 (67%) and 2 of 9 (cumulative 89%) for flecainide (P = .13). In nonhydropic fetuses, digoxin was successful in 23 of 29 (79%) and flecainide in 26 of 27 (96%) (P = .10). In hydrops, digoxin was successful in 8 of 21 (38%), flecainide alone in 6 of 7 (86%, P = .07 vs digoxin), and flecainide +/- amiodarone in 7 of 7 (100%) (P = .01). Intrauterine or neonatal death occurred in 9 of 21 hydropic fetuses treated with digoxin (43%), compared to 0 of 7 (P = .06) treated with flecainide. CONCLUSIONS: Flecainide was more effective than digoxin, especially when hydrops was present. No adverse fetal outcomes were attributed to flecainide. PMID- 27554949 TI - A regular irregular rhythm in an 80-year-old woman. PMID- 27554950 TI - Lebrikizumab for the treatment of asthma. AB - INTRODUCTION: In asthma, most commonly, 'conventional' anti-inflammatory medications represented by inhaled corticosteroids and leukotriene inhibitors are effective. In some patients however additional inhibition of the airways inflammation is necessary. Such compounds might be molecules inhibiting specifically certain inflammation pathways and lebrikizumab an anti IL-13 molecule might represent a relevant example as a potential asthma therapy. AREAS COVERED: Discussion of the rationale for the use of lebrikizumab in asthma. Analysis of the related preclinical and clinical data on lebrikizumab in asthma. EXPERT OPINION: Lebrikizumab demonstrated efficacy in an asthma subset characterized by high serum periostin levels and by heavy eosinophilic inflammation. Phase III data are necessary in order to better position this therapy in asthma including as a potential personalized approach. PMID- 27554951 TI - Post-epilepsy surgery psychogenic nonepileptic seizures. AB - OBJECTIVES: We investigated the prevalence of post-epilepsy surgery psychogenic nonepileptic seizures (PNES) in patients with drug-resistant epilepsy and the possible influence of risk factors on these seizures. METHODS: In this retrospective study, we examined data from all patients with a clinical diagnosis of drug-resistant epilepsy who underwent epilepsy surgery at Graduate Hospital and the Jefferson Comprehensive Epilepsy Center between 1986 and 2016. Postsurgical outcome was identified for up to 15 years after surgery. Diagnosis of PNES was verified in the epilepsy monitoring unit with video electroencephalography (EEG) ictal recording. Potential associated factors were assessed by comparing patients with or without postoperative PNES. RESULTS: A total of 1,105 patients were studied; 697 patients had postoperative seizures, and, of these, 27 patients (3.9%) had documented PNES after surgery. A full-scale intelligence quotient (IQ) <80 was significantly associated with post-epilepsy surgery PNES (odds ratio [OR] 2.89, p = 0.007, 95% confidence interval [CI] 1.33 6.29). A history of a preoperative psychiatric diagnosis was also significantly associated with post-epilepsy surgery PNES (OR 4.67, p = 0.0001, 95% CI 2.01 10.82). Other factors were not significantly associated with post-epilepsy surgery PNES. SIGNIFICANCE: Post-epilepsy surgery PNES should be considered when patients report recurrent seizures after epilepsy surgery. Although these seizures probably occur relatively infrequently, attention to factors such as appearance of new ictal behaviors, a preoperative history of a psychiatric disorder, and a low full-scale IQ should raise suspicion and lead to appropriate diagnostic measures. PMID- 27554952 TI - What Effect Does Transition Have on Health and Well-Being in Young People with Intellectual Disabilities? A Systematic Review. AB - BACKGROUND: Transition to adulthood might be a risk period for poor health in people with intellectual disabilities. However, the present authors could find no synthesis of evidence on health and well-being outcomes during transition in this population. This review aimed to answer this question. METHOD: PRISMA/MOOSE guidelines were followed. Search terms were defined, electronic searches of six databases were conducted, reference lists and key journals were reviewed, and grey literature was searched. Papers were selected based on clear inclusion criteria. Data were extracted from the selected papers, and their quality was systematically reviewed. The review was prospectively registered on PROSPERO: CRD42015016905. RESULTS: A total of 15 985 articles were extracted; of these, 17 met the inclusion criteria. The results of these articles were mixed but suggested the presence of some health and well-being issues in this population during transition to adulthood, including obesity and sexual health issues. CONCLUSION: This review reveals a gap in the literature on transition and health and points to the need for future work in this area. PMID- 27554953 TI - Older patients' perception of their own capacity to regain pre-fracture function after hip fracture surgery - an explorative qualitative study. AB - AIMS AND OBJECTIVES: To explore healthy older patients' perceptions of their own capacity to regain pre-fracture function in the acute phase following hip fracture surgery. BACKGROUND: The incidence of hip fractures is expected to increase. In Sweden, of the patients who sustain a hip fracture, 40 per cent are healthy and lived independently pre fracture. However, a hip fracture often results in declined functional outcomes for 40 per cent of these patients. DESIGN: The study had an explorative inductive qualitative design. METHODS: Semi structured interviews (n = 30) were conducted two to five days after hip fracture surgery. Data were analysed using manifest inductive content analysis. RESULTS: As a description of patients' perception of their own capacity to regain pre fracture function after a hip fracture, one main category emerged: To end up in a new situation with or without control. Patients expressed that they believed in recovery and thought nothing would be altered. However, since they had to adapt to the ward culture at the acute hospital, they became passive and became insecure about their future life situation. CONCLUSION: The attitudes of staff at the acute hospital can influence the outcome for hip fracture patients. Patients believe in recovery but do not receive psychological support to regain physical capacity. PMID- 27554954 TI - Why the Open Payments Program Is Likely to Provide Systematic and Transparent Data on Financial Relationships with Industry. PMID- 27554955 TI - The Reply. PMID- 27554956 TI - Health Care 2020: The Critical Role of Palliative/Hospice Care in the Reengineering of Health Care Delivery. PMID- 27554957 TI - The Reply. PMID- 27554958 TI - The Sunshine Act: Moving Forward. PMID- 27554959 TI - The Reply. PMID- 27554960 TI - Metformin in Chronic Kidney Disease - Should We Worry? PMID- 27554961 TI - The Reply. PMID- 27554962 TI - Assessing Association Among Anemia, Bleeding, and Transfusion with Long-Term Mortality. PMID- 27554963 TI - The Reply. PMID- 27554964 TI - How We Measure Heart Rate: Does it Matter? PMID- 27554965 TI - Pernicious Anemia: Another Interesting Analytic Finding. PMID- 27554966 TI - All-Cause Mortality Associated with Tumor Necrosis Factor-Alpha Inhibitor in Patients with Rheumatoid Arthritis. PMID- 27554967 TI - Effect of Huperzine A on Abeta-induced p65 of astrocyte in vitro. AB - Alzheimer's disease (AD) is the most common cause of dementia. Its pathology often accompanies inflammatory action, and astrocytes play important roles in such procedure. Rela(p65) is one of significant message factors in NF-kappaB pathway which has been reported high expression in astrocyte treated by Abeta. HupA, an alkaloid isolated from Chinese herb Huperzia serrata, has been widely used to treat AD and observations reflected that it improves memory and cognitive capacity of AD patients. To reveal its molecular mechanisms on p65, we cultured astrocytes, built Abeta-induced AD model, treated astrocytes with HupA at different concentrations, assayed cell viability with MTT, and detected p65 expression by immunohistochemistry and PCR. Our results revealed that treatment with 10 MUM Abeta1-42 for 24 h induced a significant increase of NF-kappaB in astrocytes; HupA significantly down-regulated p65 expression induced by Abeta in astrocytes. This study infers that HupA can regulate NF-kappaB pathway to treat AD. PMID- 27554968 TI - Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress. AB - Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, a model of DMD, under basal conditions and in response to seven weeks of voluntary exercise and/or activin receptor IIB ligand blocking using soluble activin receptor-Fc (sAcvR2B Fc) administration. In conjunction with reduced muscle strength, mdx muscle displayed greater levels of UPR/ER-pathway indicators including greater protein levels of IRE1alpha, PERK and Atf6b mRNA. Downstream to IRE1alpha and PERK, spliced Xbp1 mRNA and phosphorylation of eIF2alpha, were also increased. Most of the cytoplasmic and ER chaperones and mitochondrial UPR markers were unchanged in mdx muscle. Oxidized glutathione was greater in mdx and was associated with increases in lysine acetylated proteome and phosphorylated sirtuin 1. Exercise increased oxidative stress when performed independently or combined with sAcvR2B Fc administration. Although neither exercise nor sAcvR2B-Fc administration imparted a clear effect on ER stress/UPR pathways or heat shock proteins, sAcvR2B Fc administration increased protein expression levels of GRP78/BiP, a triggering factor for ER stress/UPR activation and TxNIP, a redox-regulator of ER stress induced inflammation. In conclusion, the ER stress and UPR are increased in mdx muscle. However, these processes are not distinctly improved by voluntary exercise or blocking activin receptor IIB ligands and thus do not appear to be optimal therapeutic choices for improving proteostasis in DMD. PMID- 27554970 TI - Serum free sulfhydryl status is associated with patient and graft survival in renal transplant recipients. AB - Oxidative stress contributes significantly to graft failure, morbidity and mortality in renal transplant recipients (RTR). In cells, free sulfhydryl groups (reduced thiols, R-SH) are the transducers of redox-regulated events; their oxidation status is modulated by interaction with reactive oxygen and nitrogen oxide species and thought to be in equilibrium with the circulating pool. We hypothesized that high levels of serum free thiols are a reflection of a favorable redox status and therefore positively associated with cardiovascular risk parameters, patient and graft survival in RTR. To test this, reactive free thiol groups (R-SH; corrected for total protein) were quantified in serum of 695 RTR (57% male, 53+/-13yr, functioning graft >=1yr) using Ellman's Reagent, and R SH determinants were evaluated with multivariable linear regression models. Associations between R-SH and mortality or graft failure were assessed using multivariable Cox regression analyses. In multivariable models, male gender, estimated glomerular filtration rate and serum thiosulfate positively associated with R-SH while BMI, HbA1c, corrected calcium and NT-pro-BNP inversely associated with R-SH (model R2=0.26). During follow-up (3.1 [2.7-3.9] yrs), 79 (11%) patients died and 45 (7%) patients developed graft failure. R-SH correlated inversely with all-cause mortality (HR 0.58 [95% CI 0.45-0.75] per SD increase) and graft failure (HR 0.42 [0.30-0.59]; both P<0.001), independent of parameters with which R-SH significantly associated in the multivariable regression analyses, except for NT-pro-BNP. Serum R-SH are associated with a beneficial cardiovascular risk profile and better patient and graft survival in RTR, suggesting potential usefulness as low-cost, high-throughput screening tool for whole-body redox status in translational studies. Whether R-SH modification improves long-term outcome of RTR warrants further exploration. PMID- 27554969 TI - Loss of C/EBPdelta enhances IR-induced cell death by promoting oxidative stress and mitochondrial dysfunction. AB - Exposure of cells to ionizing radiation (IR) generates reactive oxygen species (ROS). This results in increased oxidative stress and DNA double strand breaks (DSBs) which are the two underlying mechanisms by which IR causes cell/tissue injury. Cells that are deficient or impaired in the cellular antioxidant response are susceptible to IR-induced apoptosis. The transcription factor CCAAT enhancer binding protein delta (Cebpd, C/EBPdelta) has been implicated in the regulation of oxidative stress, DNA damage response, genomic stability and inflammation. We previously reported that Cebpd-deficient mice are sensitive to IR and display intestinal and hematopoietic injury, however the underlying mechanism is not known. In this study, we investigated whether an impaired ability to detoxify IR induced ROS was the underlying cause of the increased radiosensitivity of Cebpd deficient cells. We found that Cebpd-knockout (KO) mouse embryonic fibroblasts (MEFs) expressed elevated levels of ROS, both at basal levels and after exposure to gamma radiation which correlated with increased apoptosis, and decreased clonogenic survival. Pre-treatment of wild type (WT) and KO MEFs with polyethylene glycol-conjugated Cu-Zn superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) combination prior to irradiation showed a partial rescue of clonogenic survival, thus demonstrating a role for increased intracellular oxidants in promoting IR-induced cell death. Analysis of mitochondrial bioenergetics revealed that irradiated KO MEFs showed significant reductions in basal, adenosine triphosphate (ATP)-linked, maximal respiration and reserved respiratory capacity and decrease in intracellular ATP levels compared to WT MEFs indicating they display mitochondrial dysfunction. KO MEFs expressed significantly lower levels of the cellular antioxidant glutathione (GSH) and its precursor- cysteine as well as methionine. In addition to its antioxidant function, GSH plays an important role in detoxification of lipid peroxidation products such as 4-hydroxynonenal (4 HNE). The reduced GSH levels observed in KO MEFs correlated with elevated levels of 4-HNE protein adducts in irradiated KO MEFs compared to respective WT MEFs. We further showed that pre-treatment with the GSH precursor, N-acetyl L-cysteine (NAC) prior to irradiation showed a significant reduction of IR-induced cell death and increases in GSH levels, which contributed to the overall increase in clonogenic survival of KO MEFs. In contrast, pre-treatment with the GSH synthesis inhibitor- buthionine sulfoximine (BSO) further reduced the clonogenic survival of irradiated KO MEFs. This study demonstrates a novel role for C/EBPdelta in protection from basal as well as IR-induced oxidative stress and mitochondrial dysfunction thus promoting post-radiation survival. PMID- 27554971 TI - Nanoceria restrains PM2.5-induced metabolic disorder and hypothalamus inflammation by inhibition of astrocytes activation related NF-kappaB pathway in Nrf2 deficient mice. AB - Increasing studies demonstrated that air pollution (PM2.5) plays a significant role in metabolic and neurological diseases. Unfortunately, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. In this regard, we investigated the role of NF-kappaB and Nrf2 signaling in PM2.5-induced metabolic disorders and neuroinflammation, and further confirmed whether Nrf2 deficiency promoted PM2.5-induced inflammatory response by up regulating astrocytes activation and nerve injury via modulating NF-kappaB signaling pathways. Present results found that, indeed, PM2.5 challenges results in glucose tolerance, insulin resistance, dysarteriotony, peripheral inflammation, nerve injury and hypothalamus oxidative stress through astrocytes activation related NF-kappaB pathway in Nrf2 deficient mice. Moreover, in vitro study, we confirmed that activated astrocytes induced by PM2.5 were involved in pathogenesis of hypothalamic inflammation, which were significantly associated with NF-kappaB signaling. Nanoceria as potential anti-inflammatory and anti oxidant stress biomaterial has gained increasing attention. Moderate nanoceria treatment is able to restrain PM2.5-induced metabolic syndrome and inflammation. Inhibition of astrocytes activation related NF-kappaB and enhancement of Nrf2 by cerium oxide were observed in vivo and in vitro, suggesting cerium oxide inhibited hypothalamic inflammation and nerve injury by altering hypothalamic neuroendocrine alterations and decreasing glial cells activation. In addition, NF kappaB inhibitor pyrollidine dithiocarbamate (PDTC) treated primary astrocytes directly determined Nrf2 pathway could be up regulated by dose-dependent nanoceria. These results suggest a new therapeutic approach or target to protect against air pollution related diseases by cerium oxide treatment. PMID- 27554972 TI - Suppression of StarD7 promotes endoplasmic reticulum stress and induces ROS production. AB - StarD7 is an intracellular lipid transport protein identified as up-regulated in the choriocarcinoma JEG-3 cell line. StarD7 facilitates the delivery of phosphatidylcholine (PC) to the mitochondria, and StarD7 knockdown causes a reduction in phospholipid synthesis. Since inhibition of PC synthesis may lead to endoplasmic reticulum (ER) stress we hypothesized that StarD7 may be involved in maintaining cell homeostasis. Here, we examined the effect of StarD7 silencing on ER stress response and on the levels of reactive oxygen species (ROS) in the human hepatoma cell line HepG2. StarD7 knockdown induced alterations in mitochondria and ER morphology. These changes were accompanied with an ER stress response as determined by increased expression of inositol-requiring enzyme 1alpha (IRE1alpha), calnexin, glucose regulated protein 78/immunoglobulin heavy chain-binding protein (Grp78/BiP), protein kinase-like ER kinase (PERK) as well as the phosphorylated eukaryotic translation initiation factor 2, subunit 1alpha (p-eIF2alpha). Additionally, a downregulation of the tumor suppressor p53 by a degradation mechanism was observed in StarD7 siRNA cells. Furthermore, StarD7 silencing induced ROS generation and reduced cell viability after H2O2 exposure. Decreased expression of StarD7 was associated to increased levels of the heme oxygenase-1 (HO-1) and catalase enzymes as well as in catalase enzymatic activity. Finally, no changes in levels of autophagy and apoptosis markers were observed in StarD7 siRNA treated cells respect to control cells. Taken together, these results indicate that StarD7 contributes to modulate cellular redox homeostasis. PMID- 27554973 TI - Peroxiredoxin 6 expression is inversely correlated with nuclear factor-kappaB activation during Clonorchis sinensis infestation. AB - Clonorchis sinensis is a carcinogenic human liver fluke. Its infection promotes persistent oxidative stress and chronic inflammation environments in the bile duct and surrounding liver tissues owing to direct contact with worms and their excretory-secretory products (ESPs), provoking epithelial hyperplasia, periductal fibrosis, and cholangiocarcinogenesis. We examined the reciprocal regulation of two ESP-induced redox-active proteins, NF-kappaB and peroxiredoxin 6 (Prdx6), during C. sinensis infection. Prdx6 overexpression suppressed intracellular free radical generation by inhibiting NADPH oxidase2 and inducible nitric oxide synthase activation in the ESP-treated cholangiocarcinoma cells, substantially attenuating NF-kappaB-mediated inflammation. NF-kappaB overexpression decreased Prdx6 transcription levels by binding to two kappaB sites within the promoter. This transcriptional repression was compensated for by other ESP-induced redox active transcription factors, including erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor 1alpha (HIF1alpha), and CCAAT/enhancer-binding protein beta (C/EBPbeta). Distribution of immunoreactive Prdx6 and NF-kappaB was distinct in the early stages of infection in mouse livers but shared concomitant localization in the later stages. The intensity and extent of their immunoreactive staining in infected mouse livers are proportional to lesion severity and infection duration. The constitutive elevations of Prdx6 and NF kappaB during C. sinensis infection may be associated with more severe persistent hepatobiliary abnormalities mediated by clonorchiasis. PMID- 27554974 TI - Cochlear implant-related three-dimensional characteristics determined by micro computed tomography reconstruction. AB - To explore the structural characteristics of the cochlea in three-dimensional (3D) detail using 3D micro-computed tomography (mCT) image reconstruction of the osseous labyrinth, with the aim of improving the structural design of electrodes, the selection of stimulation sites, and the effectiveness of cochlear implantation. Three temporal bones were selected from among adult donors' temporal bone specimens. A micro-CT apparatus (GE eXplore) was used to scan three specimens with a voxel resolution of 45 MUm. We obtained about 460 slices/specimen, which produced abundant data. The osseous labyrinth images of three specimens were reconstructed from mCT. The cochlea and its spiral characteristics were measured precisely using Able Software 3D-DOCTOR. The 3D images of the osseous labyrinth, including the cochlea, vestibule, and semicircular canals, were reconstructed. The 3D models of the cochlea showed the spatial relationships and surface structural characteristics. Quantitative data concerning the cochlea and its spiral structural characteristics were analyzed with regard to cochlear implantation. The 3D reconstruction of mCT images clearly displayed the detailed spiral structural characteristics of the osseous labyrinth. Quantitative data regarding the cochlea and its spiral structural characteristics could help to improve electrode structural design, signal processing, and the effectiveness of cochlear implantation. Clin. Anat. 30:39-43, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27554975 TI - Tunable magnetism in metal adsorbed fluorinated nanoporous graphene. AB - Developing nanostructures with tunable magnetic states is crucial for designing novel data storage and quantum information devices. Using density functional theory, we investigate the thermodynamic stability and magnetic properties of tungsten adsorbed tri-vacancy fluorinated (TVF) graphene. We demonstrate a strong structure-property relationship and its response to external stimuli via defect engineering in graphene-based materials. Complex interplay between defect states and the chemisorbed atom results in a large magnetic moment of 7 MUB along with high in-plane magneto-crystalline anisotropy energy (MAE) of 17 meV. Under the influence of electric field, spin crossover effect accompanied by a change in the MAE is observed. The ascribed change in spin-configuration is caused by the modification of exchange coupling between defect states and a change in the occupation of d-orbitals of the metal complex. Our predictions open a promising way towards controlling the magnetic properties in graphene based spintronic and non-volatile memory devices. PMID- 27554976 TI - Effects of seasonal hypoxia on the release of phosphorus from sediments in deep water ecosystem: A case study in Hongfeng Reservoir, Southwest China. AB - Using the diffusive gradients in thin films (DGT) technique and microelectrode technique, hypoxia and its effects on the release of phosphorus (P) from sediments were carefully investigated in Hongfeng Reservoir, a typical deep-water ecosystem where eutrophication and hypoxia is still an environmental challenge in Southwest China. The results suggested that hypoxia significantly promotes the release of P from sediments and the release of P under hypoxic condition mostly comes from the release of BD-P. Together with the in-situ and high resolution evidences from DGT and microelectrode, the release of P from sediments under hypoxic condition was assumed to be coupled processes which are associated with the combined cycles of "P-Fe-S". Evidences from the present work implied that the internal P-loadings induced by hypoxia, especially after a reduction of external P-loading, should be paid more attention in eutrophic deep-water reservoirs, Southwest China. PMID- 27554977 TI - In-situ bitumen extraction associated with increased petrogenic polycyclic aromatic compounds in lake sediments from the Cold Lake heavy oil fields (Alberta, Canada). AB - Most future growth in the Alberta bituminous sands will be based on thermal in situ recovery technologies. To date, however, most attention on the environmental effects of bitumen recovery has focused on surface mining in the Athabasca region. Recent uncontrolled bitumen flow-to-surface incidents (FTS; appearance at the surface of bitumen emulsions from deep subsurface recovery zones) reported at the Cold Lake heavy oil fields highlight the need to better understand the potential role of in-situ extraction as a source of contaminants to landscapes and surface waters. We analyzed sediment cores from a lake located ~2 km away from a recent bitumen FTS incident to provide a long-term perspective on the delivery of metals, polycyclic aromatic compounds (PACs), and polychlorinated biphenyls (PCBs) to surface freshwaters, and to assess whether the onset of local in-situ bitumen extraction can be linked to contaminant increases in nearby lakes. An increase in alkyl PACs coincided with the onset and expansion of commercial in-situ bitumen extraction, and multiple lines of evidence indicate a petrogenic source for recent alkyl PAC enrichment. However, no coincident increase in vanadium (enriched in bitumen) occurred that would suggest the source of petrogenic PAC enrichment is direct input of bituminous particles. Our results show that, similar to surface mining in the Athabasca region, activities associated with in-situ extraction can increase the burden of petrogenic PACs in nearby lakes, but many questions still remain regarding the exact sources and pathways of PACs into the environment. Given that more than 80% of Alberta's bitumen reserves can only be accessed using in-situ technologies, we recommend that this be made a research priority. PMID- 27554978 TI - External lead contamination of women's nails by surma in Pakistan: Is the biomarker reliable? AB - Adverse health effects of heavy metals are a public health concern, especially lead may cause negative health impacts to human fetal and infantile development. The lead concentrations in Pakistani pregnant women's nails, used as a biomarker, were measured to estimate the lead exposure. Thirteen nail samples out of 84 nails analyzed contained lead higher than the concentration (13.6 MUg/g) of the fatal lead poisoning case, raising the possibility of an external contamination. Eye cosmetics such as surma are recognized as one of the important sources of lead exposure in Pakistan. We collected in Pakistan 30 eye cosmetics made in Pakistan, Saudi Arabia and western countries. As the metal composition analysis by energy dispersive X-ray fluorescence spectrometry revealed that some surma samples contained lead more than 96%, the surma might contaminate the nail specimen. Scanning electron microscopy observations showed that lead-containing surma consists of fine particle of galena (ore of lead sulfide) in respirable dust range (less than 10 MUm). In addition, relative in vitro bioavailability of lead in the surma was determined as 5.2%. Thus, lead-containing surma consists of inhalable and bioavailable particles, and it contributes an increased risk of lead exposure. Moreover, the relationship between the surma and the lead contaminated nails by lead isotope ratios analysis indicated the potential of lead contamination in nails by surma. These results suggest that lead in the nails was derived both from body burden of lead and external contamination by lead-containing surma. Therefore, nail is not suited as a biomarker for lead exposure in the countries where surma used, because we may overestimate lead exposure by surface lead contamination in the nail by surma. PMID- 27554979 TI - Endocrine-disruption potential of perfluoroethylcyclohexane sulfonate (PFECHS) in chronically exposed Daphnia magna. AB - Perfluoroethylcyclohexane sulfonate (PFECHS), mainly used in hydraulic fluids in aircrafts, is a member of the perfluoroalkyl sulfonate family which includes the regulated perfluorooctane sulfonate (PFOS). PFECHS has been reported in environmental samples but its toxicity to aquatic organisms is unknown. The objectives of this study were to identify biological pathways altered by sublethal exposure (12 d) of D. magna to PFECHS (0.06, 0.6, and 6 mg/L) using microarray and quantitative real-time PCR and to identify potential biomarkers to link transcriptomic to phenotypic responses. PFECHS was also quantified in surface water samples (1.04-1.38 ng/L) collected from the St. Lawrence River, Canada. Transcriptomic analyses indicated the under-regulation of vitellogenin related genes (VTG1) in PFECHS-exposed groups. PFECHS exposure also led to the up regulation of genes related to cuticle. VTG was selected as a potential cellular marker and identified in D. magna using an immuno-specific assay and quantified using Western blot and LC/MS/MS. Results indicated a decrease of VTG content in exposed D. magna which was in concordance with the transcription of VTG-related genes. No effects were observed on survival, molting, or reproduction at the individual/population levels. Overall, results suggest endocrine disruption potential for PFECHS in D. magna at concentrations higher than levels reported in the aquatic environment. PMID- 27554980 TI - Bisphenol A alters gut microbiome: Comparative metagenomics analysis. AB - Mounting evidence has shown that an alteration of the gut microbiota is associated with diet, and plays an important role in animal health and metabolic diseases. However, little is known about the influence of environmental contaminants on the gut microbial community. Bisphenol A (BPA), which is widely used for manufacturing plastic products, has recently been classified as an environmental obesogen. Although many studies have demonstrated the metabolic disrupting effects of BPA on liver and pancreatic functions, the possible effects of this synthetic compound on the metabolic diversity of the intestinal microbiota is unknown. Using 16S rRNA gene sequencing analysis on caecum samples of CD-1 mice, the present study aimed to test the hypothesis that dietary BPA intake may influence the gut microbiota composition and functions, an important attributing factor to development of the metabolic syndrome. A high-fat diet (HFD) and high-sucrose diet (HSD) were included as the positive controls for comparing the changes in the intestinal microbial profiles. Our results demonstrated a significant reduction of species diversity in the gut microbiota of BPA-fed mice. Alpha and beta diversity analyses showed that dietary BPA intake led to a similar gut microbial community structure as that induced by HFD and HSD in mice. In addition, comparative analysis of the microbial communities revealed that both BPA and a HFD favored the growth of Proteobacteria, a microbial marker of dysbiosis. Consistently, growth induction of the family Helicobacteraceae and reduction of the Firmicutes and Clostridia populations were observed in the mice fed BPA or a HFD. Collectively, our study highlighted that the effects of dietary BPA intake on the shift of microbial community structure were similar to those of a HFD and HSD, and revealed microbial markers for the development of diseases associated with an unstable microbiota. PMID- 27554981 TI - Seasonal accumulation of persistent organic pollutants on a high altitude glacier in the Eastern Alps. AB - The seasonal accumulations of perfluorinated substances (PFAS), polybrominated diphenyl ethers (PBDE) and polycyclic aromatic hydrocarbons (PAH) were measured in a 10 m shallow firn core from a high altitude glacier at Mt. Ortles (Italy, 3830 m above sea level) in South Tyrol in the Italian Eastern Alps. The most abundant persistent organic pollutants of each group were perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) (for PFASs); BDE 47, BDE 99, BDE 209 (for PBDEs) and phenanthrene (PHE), fluoranthene (FLA) and pyrene (PYR) (for PAHs). All compounds show different extents of seasonality, with higher accumulation during summer time compared to winter. This seasonal difference mainly reflects meteorological conditions with a low and stable atmospheric boundary layer in winter and strong convective activity in summer, transformation processes during the transport of chemicals and/or post depositional alterations. Change in the composition of the water-soluble PFCAs demonstrates the influence of meltwater percolation through the firn layers. PMID- 27554982 TI - Occurrence of polybrominated diphenyl ethers in indoor air and dust in Hangzhou, China: Level, role of electric appliances, and human exposure. AB - This study investigated the occurrence of 8 polybrominated diphenyl ether (PBDE) congeners from homes (n = 20), offices (n = 20), air conditioners (n = 6), and computers (n = 6). High detection frequencies for most of the congeners were observed, indicating continued widespread use of Penta-, Octa- and Deca-BDE mixtures. The median concentrations of ?PBDEs were 119 and 194 pg m-3 for home air and office air, respectively. Regarding dust, the median concentrations of ?PBDEs were 239 and 437 ng g-1 for home and office dust, respectively. The ratios of the median concentrations of BDE-209 to ?PBDEs were approximately 0.95 and 0.87 for home dust and office dust, respectively. The median concentrations of ?PBDEs were 359 ng g-1 and 350 ng g-1 for dust on air conditioner filters and the back cabinet of the computer, respectively. The ratios of the median concentrations of BDE-209 to ?PBDEs were approximately 0.58 and 0.46 for air conditioner and computer samples. Running air conditioners contributed to SigmaPBDEs in office air through direct and indirect pathways. The daily intake of PBDEs was estimated to be 2630 pg (kg bw)-1 day-1 for toddlers in homes and 319 pg (kg bw)-1 day-1 for adults in homes and offices. PMID- 27554983 TI - Plastics and microplastics on recreational beaches in Punta del Este (Uruguay): Unseen critical residents? AB - Beaches are social-ecological systems that provide several services improving human well-being. However, as one of the major coastal interfaces they are subject to plastic pollution, one of the most significant global environmental threats at present. For the first time for Uruguayan beaches, this study assessed and quantified the accumulation of plastic and microplastic debris on sandy beaches of the major touristic destination Punta del Este during the austral spring of 2013. Aiming to provide valuable information for decision-making, we performed a detailed analysis of plastic debris, their eventual transport pathways to the coast (from land and sea), and the associated persistent pollutants. The results indicated that the smallest size fractions (<20 mm) were the dominant size range, with fragments and resin pellets as types with the highest number of items. PAHs and PCBs were found in plastic debris, and their levels did not differ from baseline values reported for similar locations. The abundance of plastic debris was significantly and positively correlated with both the presence of possible land-based sources (e.g. storm-water drains, beach bars, beach access, car parking, and roads), and dissipative beach conditions. The analysis of coastal currents suggested some potential deposition areas along Punta del Este, and particularly for resin pellets, although modeling was not conclusive. From a local management point of view, the development and use of indices that allow predicting trends in the accumulation of plastic debris would be critically useful. The time dimension (e.g. seasonal) should also be considered for this threat, being crucial for locations such as Uruguay, where the use of beaches increases significantly during the summer. This first diagnosis aims to generate scientific baseline, necessary for improved management of plastic litter on beaches and their watersheds. PMID- 27554984 TI - Determination of MLN0128, an investigational antineoplastic agent, in human plasma by LC-MS/MS. AB - MLN0128, an mTOR kinase inhibitor, is currently undergoing clinical investigation for treatment of a variety of cancers. To support this work, an LC-MS/MS method has been developed for the determination of MLN0128 in human plasma. A structural analog STK040263 was used as the internal standard. Both MLN0128 and the IS were first extracted from plasma using methyl tert-butyl ether; then separated on a Waters XTerra(r) MS C18 column using a mobile phase consisting of methanol acetonitrile-10.0 mm ammonium formate (34:6:60, v/v/v) at a flow rate of 0.300 mL min-1 . Quantitation of MLN0128 was done by positive electrospray ionization tandem mass spectrometry in multiple-reaction-monitoring mode. This method has a total run time of <4 min with the retention times of 1.95 and 2.94 min for the IS and MLN0128, respectively. The method has been validated per the US Food and Drug Administration guidance for bioanalytical method validation. It has a calibration range of 0.100-50.0 ng mL-1 in human plasma with a correlation coefficient > 0.999. The overall assay accuracy and precision were <= +/- 4 and <=8%, respectively. The IS normalized recovery of MLN0128 was 98-100%. The stability studies showed that MLN0128 was stable under all tested conditions. The method developed may be useful for clinical studies of MLN0128. PMID- 27554985 TI - Secondary Structure and Membrane Topology of the Full-Length Dengue Virus NS4B in Micelles. AB - Dengue virus nonstructural protein 4B (NS4B) is a membrane protein consisting of 248 residues with a crucial role in virus replication and interference with the host innate immunity. The dengue virus serotype 3 NS4B was reconstituted into lyso-myristoyl phosphatidylglycerol (LMPG) micelles. Backbone resonance assignment of NS4B was obtained using conventional solution NMR experiments. Further studies suggested that NS4B contained eleven helices and six of them form five potential transmembrane regions. This study provides atomic level information for an important drug target to control flavivirus infections. PMID- 27554986 TI - Challenges for the in vivo quantification of brain neuropeptides using microdialysis sampling and LC-MS. AB - In recent years, neuropeptides and their receptors have received an increased interest in neuropharmacological research. Although these molecules are considered relatively small compared with proteins, their in vivo quantification using microdialysis is more challenging than for small molecules. Low microdialysis recoveries, aspecific adsorption and the presence of various multiply charged precursor ions during ESI-MS/MS detection hampers the in vivo quantification of these low abundant biomolecules. Every step in the workflow, from sampling until analysis, has to be optimized to enable the sensitive analysis of these compounds in microdialysates. PMID- 27554987 TI - Restoring touch. PMID- 27554988 TI - Robots with a sense of touch. PMID- 27554989 TI - Manganite films: Tuning phase diagrams. PMID- 27554990 TI - Porous materials: Zeolites shine bright. PMID- 27554991 TI - Drug delivery: Leukocyte-like carriers. PMID- 27554992 TI - Material witness: Bright new start for Europe? PMID- 27554993 TI - Let actual markets help assess the worth of optional very-low-nicotine cigarettes before deciding on mandatory regulations. PMID- 27554994 TI - The cellular proteome is affected by a gelsolin (BbGEL1) during morphological transitions in aerobic surface versus liquid growth in the entomopathogenic fungus Beauveria bassiana. AB - The gelsolin superfamily includes seven protein members: gelsolin, villin, adseverin, CapG, advillin, supervillin and flightless I. The gelsolin proteins are actin-binding proteins that contain three or six gelsolin-like domains, and they play important roles in remodelling actin dynamics and cellular processes in eukaryotes. The entomopathogenic fungus Beauveria bassiana expresses a unique CapG protein (BbGEL1) that contains three gelsolin-like domains. BbGEL1p is associated with actin during mycelial growth and plays an important role in fungal morphological transitions under both aerobic and submerged conditions. The DeltaBbGEL1 mutant displays abnormal spore-producing structures that reduce the conidial and blastospore yields by approximately 70% and 90% respectively. The virulence of the DeltaBbGEL1 mutant is notably reduced as indicated by topical and intrahemocoel injection assays. Two comparative proteomics analyses indicated that BbGEL1 has significantly different roles in the development of conidia and blastospores, and the results revealed the potential targets of BbGEL1 in the corresponding developmental processes. Additionally, as an overlapping downstream protein of BbGEL1, the hydrophobin-like protein gene BbHyd3 is required for conidiation but has a negative role in blastospore formation. Our findings indicate that in addition to its function as an actin-interacting protein, BbGEL1 contributes to fungal morphological transitions via broad genetic pathways. PMID- 27554995 TI - The use of a cartilage decellularized matrix scaffold for the repair of osteochondral defects: the importance of long-term studies in a large animal model. AB - OBJECTIVE: To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation. METHODS: After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur. In one joint a composite CDM-CaP scaffold was implanted (+P), in the contralateral joint a CDM only (-P) scaffold. After euthanasia at 6 months, tissues were analysed by histology, immunohistochemistry, micro-CT, biochemistry and biomechanical evaluation. RESULTS: The 8-week pilot showed encouraging formation of bone and cartilage, but incomplete defect filling. At 6 months, micro-CT and histology showed much more limited filling of the defect, but the CaP component of the +P scaffolds was well integrated with the surrounding bone. The repair tissue was fibrotic with high collagen type I and low type II content and with no differences between the groups. There were also no biochemical differences between the groups and repair tissue was much less stiff than normal tissue (P < 0.0001). CONCLUSIONS: The implants failed to produce reasonable repair tissue in this osteochondral defect model, although the CaP base in the -P group integrated well with the recipient bone. The study stresses the importance of long-term in vivo studies to assess the efficacy of cartilage repair techniques. PMID- 27554996 TI - EATING AND FEEDING DISORDERS IN THE FIRST FIVE YEARS OF LIFE: REVISING THE DC:0 3R DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD AND RATIONALE FOR THE NEW DC:0-5 PROPOSED CRITERIA. AB - Problems of eating and feeding are one of the most common reasons of referral to pediatric and infant mental health clinics. This article is drawn from work done by the ZERO TO THREE Task Force developing the DC:0-5 Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, specifically dealing with eating disorders in the first 5 years of life. The proposed changes come from both reviewing major studies and reviews published in the last 10 years and reports from clinicians collected through surveys commissioned by the Task Force. The main changes that are proposed include changes in terminology, such as Eating Disorders instead of Feeding Behavior Disorders, as well as focusing on the child's observed eating symptoms rather than on classifying the eating problems by inferred etiologies. Another major change relates to the differentiation between eating disorders that are observed beyond any specific caregiver-child relationship context and those that are confined to one specific relationship. A new category, Overeating Disorder, has been added, as it has been increasingly recognized as a significant and not rare clinical condition. Two illustrative cases are described. The proposed changes in the classification of eating disorders in the first 5 years of life are intended to encourage both clinicians and researchers to study these important disorders in young children. PMID- 27554997 TI - Investigating offering of vegetables by caregivers of preschool age children. AB - BACKGROUND: Research into the methods which caregivers use to encourage children to eat vegetables is limited, with minimal evidence about what the barriers are to offering these foods. Vegetable consumption in children is typically low, and so gaining information on these factors is vital in order to develop further caregiver-centred interventions to increase children's vegetable consumption. This study aimed to investigate the methods caregivers use to offer vegetables to preschool aged children, as well as the factors which influence whether and how caregivers present vegetables to their children. METHOD: Seventeen caregivers with a preschool aged child participated in focus groups to assess these questions. RESULTS: Thematic analysis indicated that caregivers use a range of methods to offer their children vegetables, with these methods falling into three broad categories: behavioural/active methods, passive methods and food manipulations. Influences on caregiver offering which emerged from the focus groups formed four categories: information, cost, parent factors and child factors. CONCLUSIONS: Together with large-scale quantitative data, this information can be used to shape future interventions aiming to increase children's vegetable intake as well as to tailor advice given to caregivers striving to achieve a healthful diet for their children. PMID- 27555039 TI - Fine mapping QTL for resistance to VNN disease using a high-density linkage map in Asian seabass. AB - Asian seabass has suffered from viral nervous necrosis (VNN) disease. Our previous study has mapped quantitative trait loci (QTL) for resistance to VNN disease. To fine map these QTL and identify causative genes, we identified 6425 single nucleotide polymorphisms (SNPs) from 85 dead and 94 surviving individuals. Combined with 155 microsatellites, we constructed a genetic map consisting of 24 linkage groups (LGs) containing 3000 markers, with an average interval of 1.27 cM. We mapped one significant and three suggestive QTL with phenotypic variation explained (PVE) of 8.3 to 11.0%, two significant and two suggestive QTL with PVE of 7.8 to 10.9%, for resistance in three LGs and survival time in four LGs, respectively. Further analysis one QTL with the largest effect identified protocadherin alpha-C 2-like (Pcdhac2) as the possible candidate gene. Association study in 43 families with 1127 individuals revealed a 6 bp insertion deletion was significantly associated with disease resistance. qRT-PCR showed the expression of Pcdhac2 was significantly induced in the brain, muscle and skin after nervous necrosis virus (NNV) infection. Our results could facilitate marker assisted selection (MAS) for resistance to NNV in Asian seabass and set up the basis for functional analysis of the potential causative gene for resistance. PMID- 27555041 TI - Birefringent crystals in thyroid fine-needle aspiration cytology. PMID- 27555040 TI - Use and knowledge of single dose activated charcoal: A survey of Australian doctors. AB - OBJECTIVE: The use of single dose activated charcoal (SDAC) as a means of gastric decontamination is declining. The present study examined the potential use of SDAC in common overdose scenarios by Australian emergency doctors, compared with clinical toxicologists and current guidelines. METHODS: We conducted a cross sectional survey of emergency doctors and toxicologists on the use of SDAC. The survey covered demographic data, education and previous use of SDAC and six clinical scenarios. The scenarios selected included agents not bound to SDAC, sustained-release preparations and ingestions at varying time points. Statistical calculations were performed using Fisher's exact test. RESULTS: There were 397 emergency doctors and 20 toxicologists who responded to the survey. Seventy-one per cent (n = 280/397) of emergency doctors indicated they had received some education on decontamination. Eighty-three per cent (n = 331/397) had administered SDAC during their medical career, 29% (n = 117/397) within the past year. There was a significant difference in responses between emergency doctors and toxicologists in two scenarios; a toxic paracetamol ingestion presenting within 1 h (P = 0.009) and verapamil ingestion in a 3 year old boy (P = 0.001). Toxicologists were more likely to administer SDAC in these scenarios, 89% (n = 16/18) and 88% (n = 15/17), respectively, compared with 52% (n = 197/381) and 43% (n = 158/371) of emergency doctors. CONCLUSIONS: Our study showed that there is a significant variation in the use of SDAC between toxicologists and emergency doctors in some scenarios. Clinical toxicologists are more likely to administer SDAC in certain overdose settings. It is essential to provide education on the benefits versus actual risks of SDAC in acute poisoning so that doctors will understand when to administer SDAC or seek further advice. PMID- 27555042 TI - Pure cystic adrenal space-occupying lesion: always rule out cystic pheochromocytoma. PMID- 27555043 TI - Reconstruction of a large upper arm defect with muscle sparing latissimus dorsi. AB - Reconstruction of large soft tissue defects in the upper arm represents a challenge for the reconstructive surgeon. The latissimus dorsi flap is widely used and preferred for this latter type of reconstruction due to its reliability and versatility, although sacrificing the entire muscle can lead to higher incidences of postoperative seroma and functional disability. The recent introduction of the perforator-based flap concept has led to an evolution in upper extremity reconstruction by significantly reducing donor-site morbidity and simultaneously ensuring optimal soft tissues coverage. We report a case of a large soft tissue defect of the posterolateral part of the upper arm, consequent to a sarcoma resection, in which a muscle-sparing latissimus dorsi technique was used to obtain total soft tissue coverage. A 2-year follow-up showed a satisfactory functional result and no evidence of recurrence. PMID- 27555044 TI - Staphylococcus lugdunensis: an unusual and aggressive cause of infective endocarditis. PMID- 27555045 TI - Cervical stenosis causing haematocervix and haematometra in a postmenopausal woman. PMID- 27555046 TI - Heat Transfer Analysis of an Optimized, Flexible Holder System for Freeze-Drying in Dual Chamber Cartridges Using Different State-of-the-Art PAT Tools. AB - The aim of this study was to determine the heat transfer characteristics of an optimized flexible holder device, using Tunable Diode Laser Absorption Spectroscopy, the Pressure Rise Test, and the gravimetric procedure. Two different controlled nucleation methods were tested, and an improved sublimation process, "preheated plate," was developed. Tunable Diode Laser Absorption Spectroscopy identified an initial sublimation burst phase. Accordingly, steady state equations were adapted for the gravimetric procedure, to account for this initial non-steady-state period. The heat transfer coefficient, KDCC, describing the transfer from the holder to the DCC, was the only heat transfer coefficient showing a clear pressure dependence with values ranging from 3.81E-04 cal/(g.cm2.K) at 40 mTorr to 7.38E-04 cal/(g.cm2.K) at 200 mTorr. The heat transfer coefficient, Ktot, reflecting the overall energy transfer via the holder, increased by around 24% from 40 to 200 mTorr. This resulted in a pressure independent sublimation rate of around 42 +/- 1.06 mg/h over the whole pressure range. Hence, this pressure-dependent increase in energy transfer completely compensated the decrease in driving force of sublimation. The "flexible holder" shows a substantially reduced impact of atypical radiation, improved drying homogeneity, and ultimately a better transferability of the freeze-drying cycle for process optimization. PMID- 27555047 TI - Does a bit of alcohol turn off inflammation and improve health? PMID- 27555048 TI - Association Between Polymorphisms of ADRBK1 Gene and Plasma Renin Activity in Hypertensive Patients: A Case-Control Study. AB - BACKGROUND Renin is the first step of the RAS cascade, which is a major regulator of salt-volume homeostasis. Adrenergic beta receptor kinase 1 (ADRBK1) plays important roles in regulating blood pressure via the epithelial Na+ channel (ENaC), which plays an important role in Na+ reabsorption in the renal collecting duct. The present case-control study was designed to investigate the potential relationship between polymorphisms of ADRBK1 and plasma renin activity (PRA) in hypertension. MATERIAL AND METHODS We recruited 1831 hypertensive and 422 normotensive Han Chinese subjects. Sitting PRA (ng/mL/h) was measured using radioimmunoassay method. Hypertensive patients were classified into 4 renin categories via PRA quartile. Single-nucleotide polymorphisms (SNPs) of the ADRBK1 gene (rs1894111, rs4930416, rs7127431, rs12286664, and rs3730147) were identified via TaqMan polymerase chain reaction. RESULTS Comparison of the hypertensive group and the control group showed significant differences in distribution of genotypes and alleles of rs1894111 (P<0.05). Moreover, distribution of the dominant model (CC vs. CT+TT) in rs1894111 was lower in the hypertensive group than in the control group (P<0.05). Subjects were classified into 4 subgroups based on PRA quartile; the dominant model (CC vs. CT+TT) of rs1894111 was significantly lower in the quartile 1 group (the group with the lowest PRA) than in the control group (P<0.05). Logistic regression analysis demonstrated that the dominant model (CC vs. CT+TT) of rs1894111 was significantly different in the hypertensive group (OR=1.590, 95%CI=1.022-2.474, P<0.05), particularly in the quartile 1 group (OR=1.845, 95%CI=1.119-3.042, P<0.05), but not in the quartile 4 group. CONCLUSIONS The dominant model (CC vs. CT+TT) of rs1894111 polymorphism in the ADRBK1 gene might be associated with low-renin hypertension in Han Chinese. PMID- 27555049 TI - Microscopy-based Saccharomyces cerevisiae complementation model reveals functional conservation and redundancy of N-terminal acetyltransferases. AB - N-terminal acetylation is a highly abundant protein modification catalyzed by N terminal acetyltransferases (NATs) NatA-NatG. The Saccharomyces cerevisiae protein Arl3 depends on interaction with Sys1 for its localization to the Golgi and this targeting strictly requires NatC-mediated N-terminal acetylation of Arl3. We utilized the Arl3 acetylation-dependent localization phenotype as a model system for assessing the functional conservation and in vivo redundancy of several human NATs. The catalytic subunit of human NatC, hNaa30 (Mak3), restored Arl3 localization in the absence of yNaa30, but only in the presence of either yeast or human Naa35 subunit (Mak10). In contrast, hNaa35 was not able to replace its yeast orthologue without the co-expression of hNaa30, suggesting co-evolution of the two NatC subunits. The most recently discovered and organellar human NAT, NatF/Naa60, restored the Golgi localization of Arl3 in the absence of yNaa30. Interestingly, this was also true for hNaa60 lacking its membrane-binding domain whereas hNaa50 did not complement NatC function. This in vivo redundancy reflects NatC and NatF's overlapping in vitro substrate specificities. The yeast model presented here provides a robust and rapid readout of NatC and NatF activity in vivo, and revealed evolutionary conservation of the NatC complex and redundancy between NatC and NatF. PMID- 27555050 TI - Photoluminescence in Carborane-Stilbene Triads: A Structural, Spectroscopic, and Computational Study. AB - A set of triads in which o- and m-carborane clusters are bonded to two stilbene units through Ccluster -CH2 bonds was synthesized, and their structures were confirmed by X-ray diffraction. A study on the influence of the o- and m- isomers on the absorption and photoluminescence properties of the stilbene units in solution revealed no charge-transfer contributions in the lowest excited state, as confirmed by (TD)DFT calculations. The presence of one or two B-I groups in m carborane derivatives does not affect the emission properties of the stilbenes in solution, probably due to the rather large distance between the iodo substituents and the fluorophore. Nevertheless, a significant redshift of the photoluminescence (PL) emission maximum in the solid state (thin films and powder samples) compared to solution was observed; this can be traced back to PL sensitization, most probably due to more densely packed stilbene moieties. Remarkably, the PL absolute quantum yields of powder samples are significantly higher than those in solution, and this was attributed to the restricted environment and the aforementioned sensitization. Thus, the bonding of the carborane clusters to two stilbene units preserves their PL behavior in solution, but produces significant changes in the solid state. Furthermore, iodinated species can be considered to be promising precursors for theranostic agents in which both imaging and therapeutic functions could possibly be combined. PMID- 27555051 TI - New Insights into the Mechanism of DNA Duplication by the Eukaryotic Replisome. AB - The DNA replication machinery, or replisome, is a macromolecular complex that combines DNA unwinding, priming and synthesis activities. In eukaryotic cells, the helicase and polymerases are multi-subunit, highly-dynamic assemblies whose structural characterization requires an integrated approach. Recent studies have combined single-particle electron cryo-microscopy and protein crystallography to gain insights into the mechanism of DNA duplication by the eukaryotic replisome. We review current understanding of how replication fork unwinding by the CMG helicase is coupled to leading-strand synthesis by polymerase (Pol) E and lagging strand priming by Pol alpha/primase, and discuss emerging principles of replisome organization. PMID- 27555052 TI - Metabolic Abnormalities, But Not Metabolically Healthy Obesity, Are Associated with Left Ventricular Hypertrophy. AB - BACKGROUND: Obesity has been found to be a predictor of left ventricular hypertrophy (LVH). However, studies which divide obesity into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) to study the effect of obesity on LVH have been rare. The present study aims to make clear the effects of various obese phenotypes and metabolic abnormalities on LVH. METHODS: A total of 10,804 participants were involved in this cross-sectional study. "Obesity" and "metabolically healthy" were defined as BMI >= 25kg/m2 and having none of the metabolic factors respectively. RESULTS: It was found that metabolically unhealthy non-obesity (MUNO) (OR, 2.675; 95%CI, 1.603-4.462, P < 0.001) and MUO (OR, 9.067; 95%CI, 5.474-15.020, P<0.001) were significantly associated with LVH, while it went in reverse for MHO (OR, 1.968; 95%CI, 0.560 6.920, P=0.291), after adjustment for age, race, gender, educational status, physical activity, annual income, current smoking status, current drinking status, sleep duration and BMI. And after further adjustment for metabolic abnormalities, MUNO (OR, 0.567; 95%CI, 0.316-1.018, P=0.794) and MUO (OR, 0.632; 95%CI, 0.342-1.166, P=0.142) tended not to be associated with LVH any longer. However, among the five metabolic components of metabolic abnormalities, high blood pressure (OR, 4.358; 95%CI, 3.266-5.815, P<0.001) and high waist circumference (OR, 1.530; 95%CI, 1.139-2.054, P=0.005) were significantly associated with LVH. CONCLUSIONS: Metabolic abnormalities, but not MHO, were significantly associated with LVH. In addition, metabolic abnormalities were probable to mediate the connection between MUNO/MUO and LVH. PMID- 27555053 TI - Multidisciplinary Assessment in Optimising Results of Percutaneous Patent Foramen Ovale Closure. AB - BACKGROUND: Percutaneous patent foramen ovale (PFO) closure is a therapeutic option to prevent recurrent cerebral ischaemia in patients with cryptogenic stroke and transient cerebral ischaemia (TIA). The apparent lack of benefit seen in previous randomised trials has, in part, reflected inclusion of patients with alternate mechanisms of stroke. The role of formal neurology involvement in accurately delineating the likely aetiology of stroke or TIA is crucial in appropriate identification of patients for device closure. Furthermore, as the benefits of device closure may accrue over time, long-term follow-up is essential to define the role of device closure in management of presumed cryptogenic stroke. METHODS: We retrospectively reviewed our experience with percutaneous PFO device closure since 2005. All subjects who underwent PFO closure at John Hunter and Lake Macquarie Private Hospitals were included in the study. All patients referred for device closure following cryptogenic stroke or TIA had first undergone formal neurology review with appropriate imaging and exclusion of paroxysmal atrial arrhythmia. Patients with a history of transient ischaemic attack (TIA) are frequently referred to a specialised clinic, aimed to identify patients with conditions not referable to cerebral ischaemia, with investigations initiated by the specialist clinic to elucidate an underlying aetiology. Outcome data was derived from the Hunter New England Area Local Health District Cardiac and Stroke Outcomes Unit, in addition to review of the medical record. The Cardiac and Stroke Outcomes Unit prospectively identified all patients presenting with stroke, TIA and atrial fibrillation. RESULTS: One hundred and twelve consecutive patients undergoing percutaneous patent foramen ovale closure between 2005 and 2015 were identified. The average age was 42.7 years and 57 (50.9%) patients were male. Cryptogenic stroke (68.8%) and transient cerebral ischaemia (23.2%) were the most common indications for PFO closure, with the Amplatzer device used in 83 cases (74.1%). Early residual shunting was visible in seven patients (6.3%), however on follow-up agitated saline study only two patients had residual shunt (1.8%). The annual risk of recurrent stroke or TIA was 0.21%. CONCLUSIONS: Percutaneous patent foramen ovale closure can be performed safely and effectively in patients with paradoxical embolism. In selected patients, following appropriate multidisciplinary specialist pre-procedural assessment, excellent long-term results with low incidence of recurrent events may be achieved. PMID- 27555054 TI - Efficacy and Safety of Renal Sympathetic Denervation on Dogs with Pressure Overload-Induced Heart Failure. AB - BACKGROUND: In dogs with heart failure (HF) induced by overload pressure, the role of renal sympathetic denervation (RSD) on heart failure and in the renal artery is unclear. Therefore, we investigated the efficacy and safety of RSD in dogs with pressure overload-induced heart failure. METHODS: Twenty mongrel dogs were divided into a sham-operated group, an HF group and an HF + RSD group. In the sham-operated group, the abdominal aorta was located but was not constricted, in the HF group, the abdominal aorta was constricted without RSD, and the HF+RSD group underwent RSD with constriction of the abdominal aorta after 10 weeks. Blood sampling assays, echocardiography, intravascular ultrasound (IVUS) measurement and histopathological examination were performed. RESULTS: Renal sympathetic denervation caused a significant reduction in the levels of noradrenaline (166.62+/-6.84 vs. 183.48+/-13.66 pg/ml, P<0.05), plasma renin activity (1.93+/-0.12 vs. 2.10+/-0.13 ng/mlh, P<0.05) and B-type natriuretic peptide (71.14+/-3.86 vs. 83.15+/-5.73 pg/ml, P<0.05) at eight weeks after RSD in the HF+RSD group. Compared with the HF group at eight weeks, the left ventricular internal dimension at end-diastole and end-systole were lower and the left ventricular ejection fraction was higher (all P<0.05) at eight weeks after RSD in the HF+RSD group. Intravenous ultrasound images showed no changes in the renal artery lumen, and intimal hyperplasia and vascular lumen stenosis were not observed after RSD. CONCLUSIONS: Renal sympathetic denervation could improve cardiac function in dogs with HF induced by pressure overload; RSD had no adverse influence on the renal artery. PMID- 27555055 TI - Two decades of p-phenylenediamine and toluene-2,5-diamine patch testing - focus on co-sensitizations in the European baseline series and cross-reactions with chemically related substances. AB - BACKGROUND: Cross-reactions and co-sensitizations are of great importance in understanding contact allergy and exposure sources. OBJECTIVES: To investigate common cross-reactions and co-sensitizations in p-phenylenediamine (PPD) sensitized and toluene-2,5-diamine (TDA)-sensitized individuals. METHODS: From our patch test population, 8036 patients patch tested with the European baseline series were extracted. Readings had to be performed at least on day 3 according to ICDRG guidelines. RESULTS: Two hundred and fifty-one patients were sensitized to PPD and/or TDA; 231 patients were sensitized to PPD, and 109 to TDA. Significant differences were observed regarding the strengths of patch test reactions to PPD and number of cross-reactions. For TDA, a difference was found between all reaction strengths, except between + and ++ strengths. PPD-sensitized individuals were more likely to be sensitized to carba mix, cobalt chloride, colophonium, p-tert-butyl phenolformaldehyde resin, paraben mix, and methylisothiazolinone. TDA-sensitized individuals were more often sensitized to carba mix. CONCLUSIONS: Cross-reactivity was commonly found among individuals sensitized to PPD or TDA, and was strongly related to the strength of the patch test reaction. Regarding co-sensitizations, a frequently appearing or common exposure source could not be determined. However, modification of the allergen by, for example, the skin microbiota may have caused the formation of molecules that are, for the human immune system, indistinguishable from PPD. PMID- 27555056 TI - Multilocus sequence typing of Dientamoeba fragilis identified a major clone with widespread geographical distribution. AB - The flagellated protozoan Dientamoeba fragilis is often detected in humans with gastrointestinal symptoms, but it is also commonly found in healthy subjects. As for other intestinal protozoa, the hypothesis that genetically dissimilar parasite isolates differ in their ability to cause symptoms has also been raised for D. fragilis. To date, only two D. fragilis genotypes (1 and 2) have been described, of which genotype 1 largely predominates worldwide. However, very few markers are available for genotyping studies and therefore the extent of genetic variation among isolates remains largely unknown. Here, we performed metagenomics experiments on two D. fragilis-positive stool samples, and identified a number of candidate markers based on sequence similarity to the phylogenetically related species Trichomonas vaginalis. Markers corresponding to structural genes and to genes encoding for proteases were selected for this study, and PCR experiments confirmed their belonging to the D. fragilis genome; two previously described markers (small subunit ribosomal DNA and large subunit of RNA polymerase II) were also included. Using this panel of markers, 111 isolates of human origin were genotyped, all of which, except one, belonged to genotype 1. These isolates had been collected at different times from symptomatic and asymptomatic persons of different age groups in Italy, Denmark, Brazil and Australia. By sequencing approximately 160kb from 500 PCR products, a very low level of polymorphism was observed across all the investigated loci, suggesting the existence of a major clone of D. fragilis with a widespread geographical distribution. PMID- 27555057 TI - [Transplantation strategies for hepatocellular carcinoma]. PMID- 27555058 TI - [Chewing gum after elective colon surgery]. PMID- 27555059 TI - [Fractures of carpal bones]. AB - Fractures of the carpal bones are uncommon. On standard radiographs fractures are often not recognized and a computed tomography (CT) scan is the diagnostic method of choice. The aim of treatment is to restore pain-free and full functioning of the hand. A distinction is made between stable and unstable carpal fractures. Stable non-displaced fractures can be treated conservatively. Unstable and displaced fractures have an increased risk of arthritis and non-union and should be stabilized by screws or k-wires. If treated adequately, fractures of the carpal bones have a good prognosis. Unstable and dislocated fractures have an increased risk for non-union. The subsequent development of carpal collapse with arthrosis is a severe consequence of non-union, which has a heterogeneous prognosis. PMID- 27555060 TI - [Anopexy according to Longo for hemorrhoids]. AB - The treatment for hemorrhoids ranges from conservative management to surgical procedures. The procedures are tailored to the individual grading of hemorrhoids and the individual complaints. The standard Goligher classification of the hemorrhoids is the basis for further treatment and no differentiation is made between segmental hemorrhoids and circular hemorrhoids. In the case of advanced circular hemorrhoid disease the surgical procedure with a stapler, so-called stapler anopexy, is the procedure of choice. PMID- 27555061 TI - Author's reply to Dean and Coakley. PMID- 27555063 TI - Pediatric and Neonatal Transfusion Medicine: A Roadmap for Research. PMID- 27555064 TI - Pediatric Therapeutic Apheresis: A Critical Appraisal of Evidence. AB - Apheresis technology has progressed significantly over the last 50-60 years from a predominately blood donation-based procedure to one that now includes a variety of therapeutic modalities. The last 25 years also has seen an increase in the number of diseases treated by therapeutic apheresis (TA) modalities. Because of ethical considerations, therapeutic modalities are often vetted first in adult populations before establishing utility in pediatric patients. TA is no different. The majority of published studies involve adult patients. Pediatric apheresis studies are traditionally retrospective, single-center experiences, single case reports, or case series. To confirm this, we evaluated the peer reviewed published literature to assess the level of evidence of clinical pediatric apheresis studies published in the last 21 years. Adverse events experienced by pediatric patients undergoing TA procedures and procedural modifications necessary to accommodate pediatric patients receiving TA were also explored. Consideration was given to differences in disease outcomes in pediatric vs adult patients and evolution of TA treatment indications. A systematic search of the literature yielded >1000 pediatric apheresis publications. Only 370 articles specifically assessed TA in the treatment of a pediatric disease. Of those, the majority (98%) were single-center experiences, single case reports, or case series. The remaining 2% were prospective cohort studies or randomized controlled trials. This first formal assessment of the pediatric apheresis literature confirms the findings of previous anecdotal reports and expert opinion. PMID- 27555062 TI - H3.3 demarcates GC-rich coding and subtelomeric regions and serves as potential memory mark for virulence gene expression in Plasmodium falciparum. AB - Histones, by packaging and organizing the DNA into chromatin, serve as essential building blocks for eukaryotic life. The basic structure of the chromatin is established by four canonical histones (H2A, H2B, H3 and H4), while histone variants are more commonly utilized to alter the properties of specific chromatin domains. H3.3, a variant of histone H3, was found to have diverse localization patterns and functions across species but has been rather poorly studied in protists. Here we present the first genome-wide analysis of H3.3 in the malaria causing, apicomplexan parasite, P. falciparum, which revealed a complex occupancy profile consisting of conserved and parasite-specific features. In contrast to other histone variants, PfH3.3 primarily demarcates euchromatic coding and subtelomeric repetitive sequences. Stable occupancy of PfH3.3 in these regions is largely uncoupled from the transcriptional activity and appears to be primarily dependent on the GC-content of the underlying DNA. Importantly, PfH3.3 specifically marks the promoter region of an active and poised, but not inactive antigenic variation (var) gene, thereby potentially contributing to immune evasion. Collectively, our data suggest that PfH3.3, together with other histone variants, indexes the P. falciparum genome to functionally distinct domains and contribute to a key survival strategy of this deadly pathogen. PMID- 27555065 TI - Fine structure of synaptic sites and circuits in mushroom bodies of insect brains. AB - In the insect brain, mushroom bodies represent a prominent central neuropil for multisensory integration and, crucially, for learning and memory. For this reason, special attention has been focused on its small chemical synapses. Early studies on synaptic types and their distribution, using conventional electron microscopy, and recent publications have resolved basic features of synaptic circuits. More recent studies, using experimental methods for resolving neurons, such as immunocytochemistry, genetic labelling, high resolution confocal microscopy and more advanced electron microscopy, have revealed many new details about the fine structure and molecular contents of identifiable neurons of mushroom bodies and has led to more refined modelling of functional organisation. Synaptic circuitries have been described in most detail for the calyces. In contrast, the mushroom bodies' columnar peduncle and lobes have been explored to a lesser degree. In dissecting local microcircuits, the scientist is confronted with complex neuronal compartmentalisation and specific synaptic arrangements. This article reviews classical and modern studies on the fine structure of synapses and their networks in mushroom bodies across several insect species. PMID- 27555066 TI - Punctate inner choroidopathy complicated with exudative neurosensory detachment: A favourable response to treatment with systemic corticosteroids and intravitreal ranibizumab. AB - CASE REPORT: Punctate inner choroidopathy (PIC) is a variant of multifocal choroiditis that principally affects young and healthy women. A case of this condition is described in a woman who presented with a scotoma as the main complaint. Four months after the diagnosis of PIC, she developed an exudative neurosensory detachment associated with an active focus of juxtafoveal choroiditis. Finally, with systemic corticosteroids and intravitreal ranibizumab, she made excellent progress. DISCUSSION: Intravitreal ranibizumab, associated with systemic corticosteroids, may be an effective treatment for exudative neurosensory detachment complicating PIC. PMID- 27555067 TI - The prodigious recovery of the blind woman of Villafranca. PMID- 27555068 TI - [Lymphedema as initial manifestation of malignancy]. AB - Lymphedema may result from various benign or malignant causes. In particular rapidly progressing central or unilateral lymphedema (even in case of only discrete clinical findings) should initiate an extensive diagnostic workup to detect underlying malignancies in order to enable early therapy. PMID- 27555069 TI - Osteoporosis in Pediatric Liver Transplantation. AB - Liver transplantation provides an important, often life-saving treatment for end stage liver disease. Osteoporosis post-liver transplantation has been described in adults; however, this has not been described in the pediatric population to date. We present a case of a 13-year-old female patient who underwent an orthotopic liver transplant for cryptogenic liver cirrhosis. Her immunosuppressants were tacrolimus and prednisone. Four months posttransplant, she started complaining of bilateral lower limb pain and limping while walking, progressing to a point where she was almost immobile. Magnetic resonance imagining of the pelvis showed bilateral avascular necrosis involving the weight bearing surfaces of both femoral heads, in addition to the extensive edema involving both hip joints. Bone mineral densitometry was below normal for her age at the hip and forearm. She was started on high-dose calcium and vitamin D supplement, as well as zoledronic acid with a remarkable symptomatic and functional improvement. PMID- 27555070 TI - A Solid Mass in the Chest Wall. AB - Posttransplant lymphoproliferative disorder (PTLD) is one of the most common malignancies after kidney transplantation. Different clinical and histopathological forms of PTLD related to immunosuppression can be observed after organ transplantations. We report a 42-year-old woman who had undergone deceased donor renal transplantation with an unusual presentation of PTLD. The immunosuppressive treatment was discontinued and appropriate chemotherapy was started. However, the patient died despite this treatment. Different presentations of PTLD in transplant patients should also be kept in mind. PMID- 27555071 TI - An Integrative Literature Review of Physical Activity Recommendations for Adult Renal Transplant Recipients. AB - OBJECTIVE: To establish the current state of knowledge regarding physical activity interventions for adult kidney transplant recipients. DATA SOURCES: A comprehensive literature search was conducted for the years 2009 to 2015 using 5 electronic databases: PubMed, CINAHL, Cochrane Library, Ovid, and ScienceDirect. DATA EXTRACTION: Of the 110 articles identified, only 6 met inclusion requirements. These studies were conducted between 2009 and 2015 and found that weight gain was reported most often within the first year of transplantation and that kidney transplant recipients desired early interventions to help them become more physically active. CONCLUSION: Further research is recommended to design age appropriate physical activity interventions among this aging population living with a chronic condition known to have a high prevalence of obesity and cardiovascular disease. PMID- 27555072 TI - The Health-Care Provider's Perspective of Education Before Kidney Transplantation. AB - CONTEXT: Adequate patient education is essential for preparing potential recipients for kidney transplantation. Health-care providers play a vital role in education and can identify gaps in patient understanding. OBJECTIVE: To identify deficits in patient knowledge from the perspective of a transplant multidisciplinary care team and determine whether their perceptions align with patients who have previously undergone a transplant. DESIGN: An open call was advertised for health-care providers to attend a focus group discussion regarding the educational needs of pretransplant patients in 1 Canadian center. A predetermined, semistructured set of questions was used to collect the views of transplant caregivers. A moderator, assistant moderator, and research assistant facilitated the discussion, which was transcribed verbatim. Paper surveys were distributed to collect opinions of those unable to attend or uncomfortable to voice their opinion in an open forum. Qualitative analysis software was used to identify any emergent themes. Results were compared to a previous study undertaken in transplant recipients. RESULTS: Despite pre- and posttransplant education, specific themes emerged including misconceptions about the assessment process and time on the wait list and the surgery, incongruency between patient expectations and outcome, and confusion regarding medications. Health-care provider perceptions were remarkably consistent with transplant recipients. CONCLUSION: Health-care providers identified gaps in patient understanding indicating that transplant candidates may not be internalizing what is taught. Innovative educational approaches may be needed to provide more successful patient education. Similarities between health-care provider and patient perceptions suggest that care providers are a valuable source of information. PMID- 27555073 TI - Serum Lactate Dehydrogenase is Elevated in Ischemic Acute Tubular Necrosis but Not in Acute Rejection in Kidney Transplant Patients. AB - BACKGROUND: Serum lactate dehydrogenase (LDH) levels may help to distinguish ischemic acute tubular necrosis (ATN) from acute rejection after kidney transplantation. METHODS: All kidney biopsies performed in the years 2010 to 2012 were reviewed. Serum LDH, creatinine level, clinical variables, and presence of donor-specific antibodies were recorded before the biopsy. RESULTS: Overall 150 biopsies were included. Ischemic ATN was diagnosed in 45 biopsies and acute cellular-mediated rejection and/or antibody-mediated rejection in 59 biopsies, 38 of which were accompanied by ATN. Serum LDH was elevated in 23 (51%) of 45 cases with ischemic ATN versus 15 (14%) of 105 cases with other diagnoses ( P < .0001). Median serum LDH was 478 U/L (range 277-2018) for ischemic ATN and 372 U/L (range 191-748) for all other diagnoses ( P < .001). When delayed graft function or primary nonfunctioning grafts were caused by ischemic ATN, serum LDH was elevated in 58% of cases, but when caused by acute rejection, LDH was normal in 88% of cases ( P = .02). CONCLUSIONS: There is a strong association between elevated serum LDH 1 to 3 days before performing kidney biopsy and the diagnosis of ischemic ATN after kidney transplantation, especially at the immediate posttransplantation period. Normal serum LDH at this period should raise a suspicion of acute rejection. PMID- 27555074 TI - Role of Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation. AB - CONTEXT: The management of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is challenging, especially if it is not treatable by surgery or embolization. OBJECTIVES: The present study aims to compare the survival rates of liver transplanted patients receiving sorafenib or best supportive care (BSC) for HCC recurrence not amenable to curative intent treatments. DESIGN: This is a retrospective comparative study on a prospectively maintained database. PARTICIPANTS: Liver transplanted patients with untreatable HCC recurrence receiving BSC (n = 18) until 2007 or sorafenib (n = 15) thereafter were compared. RESULTS: No group difference was observed for demographic characteristics at the time of transplantation and at the time of HCC recurrence. On the explant pathology of the native liver, 81.2% patients were classified within the Milan criteria, and 53.1% presented with microvascular invasion. Hepatocellular carcinoma recurrence was diagnosed 17.8 months (standard deviation: 14.5) after LT, with 17 (53.1%) patients presenting with early recurrence (<=12 months). The 1-year survival from untreatable progression of HCC recurrence was 23.9% for the BSC and 60% for the sorafenib group ( P = .002). The type of treatment (sorafenib vs BSC) was the sole independent predictor of survival (hazard ratio: 2.98; 95% confidence interval: 1.09-8.1; P = .033). In the sorafenib group, 8 (53.3%) patients required dose reduction, and 2 (13.3%) patients discontinued the treatment due to intolerable side effects. CONCLUSION: Sorafenib improves survival and is superior to the BSC in cases of untreatable posttransplant hepatocellular carcinoma recurrence. PMID- 27555075 TI - Having a Healthy Birth With a 100-Year-Old Liver. AB - In March 2008, a 19-year-old woman required emergency liver transplantation due to acute-on-chronic liver failure. No living donor candidate was available. A marginal deceased liver that had been rejected by all the other centers was offered. The liver belonged to a 93-year-old woman and contained a hydatid cyst. Because of low donation rates in our country, we chose to accept the 93-year-old liver. The postoperative early and late courses were fortunately uneventful. Five years after transplantation, the woman became pregnant and gave birth to a healthy female baby. Today, the ages of the baby, mother, and the transplanted liver are 1, 26, and 100 years, respectively. A nonagenarian liver with hydatid disease was able to sustain its viability in a younger woman after transplant and also helped her bring in a new life into the world. PMID- 27555076 TI - Vitamin D Treatment Effect on Serum Endocan and High-Sensitivity C-Reactive Protein Levels in Renal Transplant Patients. AB - CONTEXT: Endocan is a marker showing endothelial dysfunction and inflammation. Significantly increased endocan levels have been observed in serum of patients with sepsis and cancer. OBJECTIVE: Our aim was to investigate the relationship between vitamin D treatment and serum endocan and high-sensitivity C-reactive protein (hs-CRP) levels as inflammatory markers in transplant patients. DESIGN: Prospective. SETTING: Nephrology clinic. PATIENTS: Thirty-eight renal transplant patients with serum 25-hydroxy-vitamin D (25-OH-vitamin D) levels below 20 ng/mL and transplanted at least 12 months. INTERVENTION: One-time oral dose of 300 000 IU vitamin D3. MAIN OUTCOME MEASURES: Before and after vitamin D treatment, serum endocan, hs-CRP, calcium, phosphorus, and parathyroid hormone (PTH) levels were measured. RESULTS: Median serum endocan and PTH values before vitamin D were significantly higher than those of after treatment values ( P = .001 and P < .001, respectively). On the other hand, serum total calcium and phosphorus levels before vitamin D treatment were lower than the values obtained after vitamin D treatment ( P = .0013 and P < .001, respectively). Serum hs-CRP was lower after vitamin D therapy than before, but the difference was not statistically significant ( P = .06). A moderate negative correlation was determined between endocan and 25-OH-vitamin D levels after treatment with vitamin D ( r = -.36, P = .02). CONCLUSION: This study has revealed that vitamin D treatment reduced markers of endothelial dysfunction in patients with renal transplantation and vitamin D deficiency. PMID- 27555077 TI - Fatal Graft-Versus-Host Disease Following Adult-To-Adult Living Donor Liver Transplantation From an HLA Nonhomozygous Donor. AB - The use of a human leukocyte antigen (HLA) homozygous donor to a haploidentical recipient is a well-documented cause of transfusion-associated graft-versus-host disease (GVHD). Several authors have reported that use of a graft from an HLA homozygous donor with 1-way donor-recipient HLA matching led to an extremely high risk of developing GVHD in LDLT. We have experienced a fatal case of acute GVHD following adult-to-adult LDLT from a donor who was heterozygous at a single HLA locus. A 53-year-old female underwent LDLT for chronic hepatitis B and recurrent hepatocellular carcinoma. The donor was her 23-year-old son. The HLA phenotype of the donor was not homozygous (A24, -; B54, -; DR4, 9) and revealed one-way donor dominant HLA matching at two loci with the recipient (A2, 24; B48, 54; DR4, 12). On the fortieth postoperative day, the patient showed erythematous skin lesions. Skin biopsy revealed typical findings of GVHD. Donor-derived chimerism was demonstrated by performing fluorescent in situ hybridization (FISH) using the recipient's skin tissue. As the clinical course deteriorated, etanercept was started in addition to broad-spectrum antibiotics but there was no improvement. As multi-organ failure progressed, the patient succumbed to death on the 54th postoperative day, which was 2 weeks after onset of GVHD. The prevention of GVHD is more important since the results of treatment have been disappointing. We have experienced a fatal case of acute GVHD following adult-to-adult LDLT from a HLA non-homozygous donor. HLA heterozygosity at a single locus does not preclude the possibility of developing GVHD following adult-to-adult LDLT. PMID- 27555078 TI - Surgery is not always best for lumbar spinal stenosis. PMID- 27555079 TI - An antimicrobial protein of the Riptortus pedestris salivary gland was cleaved by a virulence factor of Serratia marcescens. AB - Recently, our group demonstrated that the bean bug, Riptortus pedestris, is a good experimental symbiosis model to study the molecular cross-talk between the host insect and the gut symbiont. The Burkholderia symbiont is orally acquired by host nymphs from the environment in every generation. However, it is still unclear how Riptortus specifically interacts with entomopathogens that are abundant in the environmental soil. In preliminary experiments, we observed that a potent entomopathogen, Serratia marcescens, can colonize the midgut of Riptortus insects and was recovered from the midgut when Serratia cells were orally administered, suggesting that this pathogenic bacterium can escape host immune defenses in the salivary fluid. We examined how orally fed Serratia cells can survive in the presence of antimicrobial substances of the Riptortus salivary fluid. In this study, a 15 kDa trialysin-like protein from the salivary gland of R. pedestris and a potent virulence factor of Serratia cells, a serralysin metalloprotease, from the culture medium of S. marcescens were successfully purified to homogeneity. When the purified Riptortus trialysin (rip-trialysin) was incubated with purified serralysin, rip-trialysin was specifically hydrolyzed by serralysin, leading to the loss of antimicrobial activity. These results clearly demonstrated that a potent virulent metalloprotease of S. marcescens functions as a key player in the escape from the salivary fluid-mediated host immune response, resulting in successful colonization of S. marcescens in the host midgut. PMID- 27555080 TI - Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts. AB - OBJECTIVES: Explicit reporting of absolute measures is important to ensure treatment effects are correctly interpreted. We examined the extent to which authors report absolute effects for patient-important outcomes in abstracts of systematic review (SR). STUDY DESIGN AND SETTING: We searched OVID MEDLINE and Cochrane Database of Systematic Reviews to identify eligible SRs published in the year 2010. Citations were stratified into Cochrane and non-Cochrane reviews, with repeated random sampling in a 1:1 ratio. Paired reviewers screened articles and recorded abstract characteristics, including reporting of effect measures for the most patient-important outcomes of benefit and harm. RESULTS: We included 96 Cochrane and 94 non-Cochrane reviews. About 117 (77.5%) relative measures were reported in abstracts for outcomes of benefit, whereas only 34 (22.5%) absolute measures were reported. Similarly, for outcomes of harm, 41 (87.2%) relative measures were provided in abstracts, compared with only 6 (12.8%) absolute measures. Eighteen (9.5%) abstracts reported both absolute and relative measures for outcomes of benefit, whereas only two (1.1%) abstracts reported both measures for outcomes of harm. Results were similar between Cochrane and non-Cochrane reviews. CONCLUSION: SR abstracts seldom report measures of absolute effect. Journal editors should insist that authors report both relative and absolute effects for patient-important outcomes. PMID- 27555081 TI - Unreported formal assessment of unblinding occurred in 4 of 10 randomized clinical trials, unreported loss of blinding in 1 of 10 trials. AB - OBJECTIVES: Randomized clinical trials often involve blinding as a methodological procedure to avoid bias. Unfortunately, blinding procedures may be unsuccessful, but the risk of unblinding is rarely reported in trial publications. Our primary aim was to assess the occurrence of unreported assessment of the risk of unblinding in randomized clinical trials and to describe the assessment procedures involved. Our secondary aim was to assess the occurrence of unreported suspected or overt unblinding and the mechanisms of unblinding. STUDY DESIGN AND SETTING: A Web-based questionnaire survey of authors to trial publications which did not report risk of unblinding. Respondents were corresponding authors to a random sample of PubMed indexed articles on blinded randomized clinical trials published in 2010. We initially sampled 300 publications of which 24 reported on risk of unblinding. RESULTS: Of the 276 contacted trial authors, 129 (47%) responded. Assessment of the risk of unblinding was conducted in 56 trials (43%), often based on a pretrial evaluation involving a group of healthy assessors trying to identify differences between experimental and control interventions. When we included informal assessments of the risk of unblinding, the number of trials assessing the risk of unblinding increased to 75 (58%). Suspected or overt unblinding occurred in 14 trials (11%), mostly based on perceptible differences between experimental and control interventions. CONCLUSION: Approximately 4 of 10 trials assessed risk of unblinding without reporting such assessments in the trial publication, and approximately 1 in 10 trials identified cases of overt or suspected unblinding, also without reporting them. Unblinding is not an exceptional event in randomized clinical trials; it occurs regularly but is rarely reported. PMID- 27555082 TI - Registry-based randomized controlled trials- what are the advantages, challenges, and areas for future research? AB - Registry-based randomized controlled trials are defined as pragmatic trials that use registries as a platform for case records, data collection, randomization, and follow-up. Recently, the application of registry-based randomized controlled trials has attracted increasing attention in health research to address comparative effectiveness research questions in real-world settings, mainly due to their low cost, enhanced generalizability of findings, rapid consecutive enrollment, and the potential completeness of follow-up for the reference population, when compared with conventional randomized effectiveness trials. However several challenges of registry-based randomized controlled trials have to be taken into consideration, including registry data quality, ethical issues, and methodological challenges. In this article, we summarize the advantages, challenges, and areas for future research related to registry-based randomized controlled trials. PMID- 27555083 TI - Longstanding Challenges in Lung Cancer: Are We Meeting Them? PMID- 27555085 TI - The role of crossover operator in evolutionary-based approach to the problem of genetic code optimization. AB - One of theories explaining the present structure of canonical genetic code assumes that it was optimized to minimize harmful effects of amino acid replacements resulting from nucleotide substitutions and translational errors. A way to testify this concept is to find the optimal code under given criteria and compare it with the canonical genetic code. Unfortunately, the huge number of possible alternatives makes it impossible to find the optimal code using exhaustive methods in sensible time. Therefore, heuristic methods should be applied to search the space of possible solutions. Evolutionary algorithms (EA) seem to be ones of such promising approaches. This class of methods is founded both on mutation and crossover operators, which are responsible for creating and maintaining the diversity of candidate solutions. These operators possess dissimilar characteristics and consequently play different roles in the process of finding the best solutions under given criteria. Therefore, the effective searching for the potential solutions can be improved by applying both of them, especially when these operators are devised specifically for a given problem. To study this subject, we analyze the effectiveness of algorithms for various combinations of mutation and crossover probabilities under three models of the genetic code assuming different restrictions on its structure. To achieve that, we adapt the position based crossover operator for the most restricted model and develop a new type of crossover operator for the more general models. The applied fitness function describes costs of amino acid replacement regarding their polarity. Our results indicate that the usage of crossover operators can significantly improve the quality of the solutions. Moreover, the simulations with the crossover operator optimize the fitness function in the smaller number of generations than simulations without this operator. The optimal genetic codes without restrictions on their structure minimize the costs about 2.7 times better than the canonical genetic code. Interestingly, the optimal codes are dominated by amino acids characterized by polarity close to its average value for all amino acids. PMID- 27555084 TI - Aristolochic Acid in the Etiology of Renal Cell Carcinoma. AB - BACKGROUND: Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)-DNA adducts. Here we investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC). METHODS: We conducted a population-based case-control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole-exome sequences of ccRCC tumors from 10 Taiwanese ccRCC patients with prior exposure to AA were determined. RESULTS: Cumulative ingestion of more than 250 mg of AA increased risk of ccRCC (OR, 1.25), and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Furthermore, the distinctive AA mutational signature was evident in six of 10 sequenced ccRCC exomes from Taiwanese patients. CONCLUSIONS: This study strongly suggests that AA contributes to the etiology of certain RCCs. IMPACT: The current study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiologic, molecular, and genetic data in the investigation of cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1600-8. (c)2016 AACR. PMID- 27555086 TI - Exact numerical calculation of fixation probability and time on graphs. AB - The Moran process on graphs is a popular model to study the dynamics of evolution in a spatially structured population. Exact analytical solutions for the fixation probability and time of a new mutant have been found for only a few classes of graphs so far. Simulations are time-expensive and many realizations are necessary, as the variance of the fixation times is high. We present an algorithm that numerically computes these quantities for arbitrary small graphs by an approach based on the transition matrix. The advantage over simulations is that the calculation has to be executed only once. Building the transition matrix is automated by our algorithm. This enables a fast and interactive study of different graph structures and their effect on fixation probability and time. We provide a fast implementation in C with this note (Hindersin et al., 2016). Our code is very flexible, as it can handle two different update mechanisms (Birth death or death-Birth), as well as arbitrary directed or undirected graphs. PMID- 27555087 TI - Role of neuroimaging in children with acute lymphoblastic leukemia and central nervous system involvement at diagnosis. AB - BACKGROUND: Each year approximately 200 children and adolescents are diagnosed with acute lymphoblastic leukemia (ALL) in the five Nordic countries, and 3% of these have central nervous system (CNS) involvement confirmed by leukemic cells in the cerebrospinal fluid (CSF) or neurological symptoms. We sought to determine the significance of neuraxis imaging in such patients. PROCEDURE: Magnetic resonance images of children aged 1-17.9 with CNS leukemia at diagnosis of ALL were centrally reviewed and clinical data were retrieved from the medical records and the Nordic leukemia registry. Patients were diagnosed in the period 2000-2012 in Sweden, Finland, or Denmark. RESULTS: The cohort comprised 1,877 patients, and 66 (3.5%) had CNS involvement. Forty-five percent (30/66) had CNS related symptoms. Symptoms included vomiting, facial palsy, headache, visual symptoms, and impaired hearing. CNS imaging was performed in 32 of 66 children (48%), and confirmed CNS involvement in 6 of 21 patients with symptoms (29%) and 5 of 11 (45%) without (P = 0.44). There was no difference in the overall survival between CNS-positive patients with and without signs of leukemic involvement by imaging (P = 0.53). CONCLUSIONS: Radiological imaging of asymptomatic children with CNS leukemia at diagnosis lacks clinical importance, but may be useful in patients with cranial nerve symptoms and negative CSF, as well as for follow-up. Imaging of symptomatic patients is warranted in order to exclude other causes underlying the symptoms. PMID- 27555088 TI - Altered gene expression in hippocampus and depressive-like behavior in young adult female mice by early protein malnutrition. AB - Perinatal development represents a critical period in the life of an individual. A common cause of poor development is that which comes from undernutrition or malnutrition. In particular, protein deprivation during development has been shown to have deep deleterious effects on brain's growth and plasticity. Early life stress has also been linked with an increased risk to develop different psychopathologies later in life. We have previously shown that perinatal protein malnutrition in mice leads to the appearance of anxiety-related behaviors in the adulthood. We also found evidence that the female offspring was more susceptible to the development of depression-related behaviors. In the present work, we further investigated this behavior together with its molecular bases. We focused our study on the hippocampus, as it is a structure involved in coping with stressful situations. We found an increase in immobility time in the forced swimming test in perinatally malnourished females, and an alteration in the expression of genes related with neuroplasticity, early growth response 1, calcineurin and c-fos. We also found that perinatal malnutrition causes a reduction in the number of neurons in the hippocampus. This reduction, together with altered gene expression, could be related to the increment in immobility time observed in the forced swimming test. PMID- 27555090 TI - Intensive care units in Turkish hospitals: do they meet the minimum standards? AB - BACKGROUND: International and national standards for ICUs have been developed to ensure patient safety and provide effective and efficient service in these units. However, global economic crises along with shortages in professional health care staff affect the ability of ICUs to meet and maintain these standards. AIMS AND OBJECTIVES: The aim of this study was to ascertain whether the equipment and workforce in intensive care units (ICUs) in Turkish hospitals meet current ICU standards. DESIGN: This is a descriptive study based on the results of a survey questionnaire. METHODS: In total, 145 ICUs in university and private hospitals in Turkey participated in this survey. Data collection was done by means of a survey questionnaire that assessed the current equipment and workforce in these ICUs. RESULTS: We found that 97.0% of the occupied beds in the ICUs had a cardiac monitor. Crash-carts were present in every ICU. Transport monitors and transport ventilators were available in two of three and in one of two ICUs, respectively. In 82.8% of the ICUs, a physician (as a trainee level) was present at all times, while only a few ICUs had ICU-care team members such as respiratory- and physiotherapist, clinical pharmacists and dieticians available. There was a general shortage of nursing staff in ICUs. CONCLUSION: Currently, ICUs in Turkish hospitals meet the majority of standards for ICU equipment, but they fail to meet both the international and national standards for ICU workforce requirement. CLINICAL RELEVANCE: Hospital and ICU managers could use our findings to compare their facilities with others or to identify areas in need of improvement. PMID- 27555089 TI - Differences in contents of organochlorine impurities do not influence responses to patch testing with Majantol(r). AB - BACKGROUND: Majantol(r) [2,2-dimethyl-3-(3-methylphenyl)propan-1-ol; CAS no. 103694-68-4] has been identified as a contact allergen in humans, despite negative animal tests. Hence impurities, specifically organochlorines, in Majantol(r) might have been the reason for positive patch test reactions in the past. OBJECTIVES: To assess elicitation via patch testing with a standard market quality version of Majantol(r) ('normal') with a normal content of organochlorine impurities, as compared with an ultra-purified version of Majantol(r) ('pure'), without detectable organochlorine impurities. METHODS: Between 1 October 2013 and 31 December 2014, two different Majantol(r) patch test preparations of the above mentioned quality were tested 5% pet. in parallel in the 'monitor series', that is, together with the baseline series, in 8005 consecutive patients from 33 departments of dermatology of the Information Network of Departments of Dermatology (IVDK). RESULTS: Fifty-three of 7740 [0.69% (95%CI: 0.51-0.87)] patch tested patients reacted to at least one Majantol(r) preparation. The majority (n = 32) (60.4%) reacted to both preparations, 13 (24.5%) reacted to the 'normal' version only, and 8 (15.1%) reacted to the 'pure' version only. There was good concordance between results [Cohen's kappa 0.75 (95%CI: 0.65-0.85)], and there was no significant difference in frequency or intensity between the two preparations. More doubtful or irritant reactions than positive reactions were observed, and> 80% of all positive reactions were weak positive. CONCLUSION: Organochlorine impurities are very probably not the cause of allergic reactions to Majantol(r). PMID- 27555092 TI - Prevention of Anaphylaxis: The Role of the Epinephrine Auto-Injector. AB - Anaphylaxis is a life-threatening condition, with at-risk individuals remaining at chronic high risk of recurrence. Anaphylaxis is frequently underrecognized and undertreated by healthcare providers. The first-line pharmacologic intervention for anaphylaxis is epinephrine, and guidelines uniformly agree that its prompt administration is vital to prevent progression, improve patient outcomes, and reduce hospitalizations and fatalities. Healthcare costs potentially associated with failure to provide epinephrine (hospitalizations and emergency department visits) generally exceed those of its provision. At-risk patients are prescribed epinephrine auto-injectors to facilitate timely administration in the event of an anaphylactic episode. Despite guideline recommendations that patients carry 2 auto-injectors at all times, a significant proportion of patients fail to do so, with cost of medicine cited as one reason for this lack of adherence. With the increase of high-deductible healthcare plans, patient adherence to recommendations may be further affected by increased cost sharing. The recognition and classification of epinephrine as a preventive medicine by both the US Preventive Services Task Force and insurers could increase patient access, improve outcomes, and save lives. PMID- 27555091 TI - Early cardiac electrographic and molecular remodeling in a model of status epilepticus and acquired epilepsy. AB - OBJECTIVES: A myriad of acute and chronic cardiac alterations are associated with status epilepticus (SE) including increased sympathetic tone, rhythm and ventricular repolarization disturbances. Despite these observations, the molecular processes underlying SE-associated myocardial remodeling remain to be identified. Here we determined early SE-associated myocardial electrical and molecular alterations using a model of SE and acquired epilepsy. METHODS: We performed electrocardiography (ECG) assessments in rats beginning at 2 weeks following kainate-induced SE, and calculated short-term variability (STV) of the corrected QT intervals (QTc) as a marker of ventricular stability. Using western blotting, we quantified myocardial beta1-adrenergic receptors (beta1-AR) and ventricular gap junction protein connexin 43 (Cx43) levels as makers of increased sympathetic tone. We determined the activation status of three kinases associated with sympathetic stimulation and their downstream ion channel targets: extracellular signal-regulated kinase (ERK), protein kinase A (PKA), Ca2+ /calmodulin-dependent protein kinase II (CamKII), hyperpolarization-activated cyclic nucleotide-gated channel subunit 2 (HCN2), and voltage-gated potassium channels 4.2 (Kv4.2 ). We investigated whether SE was associated with altered Ca2+ homeostasis by determining select Ca2+ -handling protein levels using western blotting. RESULTS: Compared with the sham group, SE animals exhibited higher heart rate, longer QTc interval, and higher STV beginning at 2 weeks following SE. Concurrently, the myocardium of SE rats showed lower beta1-AR and higher Cx43 protein levels, higher levels of phosphorylated ERK, PKA, and CamKII along with decreased HCN2 and Kv4.2 channel levels. In addition, the SE rats had altered proteins levels of Ca2+ -handling proteins, with decreased Na+ /Ca2+ exchanger-1 and increased calreticulin. SIGNIFICANCE: SE triggers early molecular alterations in the myocardium consistent with increased sympathetic tone and altered Ca2+ homeostasis. These changes, coupled with early and persistent ECG abnormalities, suggest that the observed molecular alterations may contribute to SE-associated cardiac remodeling. Additional mechanistic studies are needed to determine potential causal roles. PMID- 27555093 TI - The Association Between Barium Examination and Subsequent Appendicitis: A Nationwide Population-Based Study. AB - OBJECTIVE: The incidence and association between appendicitis and barium examination (BE) remain unclear. Such potential risk may be omitted. We conducted a longitudinal, nationwide, population-based cohort study to investigate the association between BE and appendicitis risk. METHODS: From the Taiwan National Health Insurance Research Database, a total of 24,885 patients who underwent BE between January 1, 2000 and December 31, 2010 were enrolled in a BE cohort; an additional 98,384 subjects without BE exposure were selected as a non-BE cohort, matched by age, sex, and index date. The cumulative incidences of subsequent appendicitis in the BE and non-BE cohorts were assessed using the Kaplan-Meier curves and log-rank test. Cox proportional hazards regression analyses were employed to calculate the appendicitis risk between the groups. RESULTS: The cumulative incidence of appendicitis was higher in the BE cohort than in the non BE cohort (P = .001). The overall incidence rates of appendicitis for the BE and non-BE cohorts were 1.19 and 0.80 per 1000 person-years, respectively. After adjustment for sex, age, and comorbidities, the risk of appendicitis was higher in the BE cohort (adjusted hazard ratio = 1.46, 95% confidence interval = 1.23 1.73) compared with the non-BE cohort, especially in the first 2 months (adjusted hazard ratio = 9.72, 95% confidence interval = 4.65-20.3). CONCLUSIONS: BE was associated with an increased, time-dependent appendicitis risk. Clinicians should be aware of this potential risk to avoid delayed diagnoses. PMID- 27555094 TI - Essential Facts About Mosquito Control and Zika Virus. AB - The threat to persons living in the southern United States from Zika virus (ZIKV) is both significant and ongoing. Although there are several modes of transmission of ZIKV to humans, mosquito transmission is the primary avenue by which persons become infected. Only 2 mosquito species are likely able to transmit ZIKV to humans in the United States, and information about their biology and control is important to physicians and public health officials. This article discusses ZIKV mosquito vector ecology and control, with emphasis on source reduction and personal protection. PMID- 27555095 TI - Mitral Regurgitation and Increased Risk of All-Cause and Cardiovascular Mortality in Patients with Type 2 Diabetes. AB - BACKGROUND: Mitral regurgitation is the most common heart valve disease in the general population, but little is known about the prevalence and prognostic implications of mitral regurgitation in patients with type 2 diabetes. METHODS: We retrospectively analyzed the data from 814 outpatients with type 2 diabetes who had undergone a conventional echocardiography for clinical reasons during the years 1992-2007. Mitral regurgitation was evaluated by using an integrated multiparametric echocardiographic approach. The study outcomes were all-cause and cardiovascular mortality. RESULTS: At baseline, 261 (32%) patients had mitral regurgitation (25% mild, 5% moderate, and 2% severe). Over a mean follow-up of 9 years, 120 (14%) patients died, 50 of them from cardiovascular causes. Compared with those without valve disease, patients with mild mitral regurgitation had a 3.3-fold increased risk of all-cause mortality, whereas those with moderate-to severe mitral regurgitation had a 5.1-fold increased risk of all-cause mortality. Results remained statistically significant after adjustment for multiple potential confounders. Similar results were found for cardiovascular mortality. CONCLUSIONS: Mitral regurgitation is a common pathologic condition in patients with type 2 diabetes and is independently associated with an increased risk of both all-cause and cardiovascular mortality, even if the severity of mitral regurgitation is mild. PMID- 27555096 TI - Public Policy and Physician Involvement: Removing Barriers, Enhancing Impact. PMID- 27555098 TI - The amino-terminal hydrophilic region of the vacuolar transporter Avt3p is dispensable for the vacuolar amino acid compartmentalization of Schizosaccharomyces pombe. AB - Avt3p, a vacuolar amino acid exporter (656 amino acid residues) that is important for vacuolar amino acid compartmentalization as well as spore formation in Schizosaccharomyces pombe, has an extremely long hydrophilic region (approximately 290 amino acid residues) at its N-terminus. Because known functional domains have not been found in this region, its functional role was examined with a deletion mutant avt3(?1-270) expressed in S. pombe avt3? cells. The deletion of this region did not affect its intracellular localization or vacuolar contents of basic amino acids as well as neutral ones. The defect of avt3Delta cells in spore formation was rescued by the expression of avt3+ but was not completely rescued by the expression of avt3(?1-270). The N-terminal region is thus dispensable for the function of Avt3p as an amino acid exporter, but it is likely to be involved in the role of Avt3p under nutritional starvation conditions. PMID- 27555097 TI - Physical Activity in Obese Type 2 Diabetes After Gastric Bypass or Medical Management. AB - BACKGROUND: The purpose of this study was to compare effects of Roux-en-Y gastric bypass versus a multidisciplinary, group-based medical diabetes and weight management program on physical fitness and behaviors. METHODS: Physical behavior and fitness were assessed in participants of the study Surgery or Lifestyle With Intensive Medical Management in the Treatment of Type 2 Diabetes (SLIMM-T2D) (NCT01073020), a randomized, parallel-group trial conducted at a US academic hospital and diabetes clinic with 18- to 24-month follow-up. Thirty-eight type 2 diabetes patients with hemoglobin A1c >=6.5% and body mass index 30-42 kg/m2 were randomized to Roux-en-Y gastric bypass or the medical program. A 6-minute walk test to evaluate fitness, self-reported physical activity, standardized physical surveys, and cardiometabolic risk assessment were performed at baseline and after intervention. RESULTS: Both groups similarly improved 6-minute walk test distance, with greater improvements in oxygen saturation and reduced heart rate after surgery. Self-reported physical activity improved similarly at 18-24 months after interventions, although exercise increased gradually after surgery, whereas early substantial increases in the medical group were not fully sustained. Self reported total and physical health were similar by Short Form-36 but improved more in the Impact of Weight on Quality of Life survey after surgery. Improvement in cardiovascular risk scores, HbA1c, and body mass index were greater after surgery. CONCLUSION: In this small, randomized study, both interventions led to therapeutic lifestyle changes and improved objective and self-reported physical fitness. Greater improvements in heart rate, oxygen saturation, and perceived impact of weight on health were seen after surgery, which could be attributable to greater weight loss. The clinical importance of these improvements with greater weight loss warrants further investigation. PMID- 27555099 TI - Erratum: On the use of composite analyses to form physical hypotheses: An example from heat wave - SST associations. PMID- 27555100 TI - Stability and complexity in model meta-ecosystems. AB - The diversity of life and its organization in networks of interacting species has been a long-standing theoretical puzzle for ecologists. Ever since May's provocative paper challenging whether 'large complex systems [are] stable' various hypotheses have been proposed to explain when stability should be the rule, not the exception. Spatial dynamics may be stabilizing and thus explain high community diversity, yet existing theory on spatial stabilization is limited, preventing comparisons of the role of dispersal relative to species interactions. Here we incorporate dispersal of organisms and material into stability-complexity theory. We find that stability criteria from classic theory are relaxed in direct proportion to the number of ecologically distinct patches in the meta-ecosystem. Further, we find the stabilizing effect of dispersal is maximal at intermediate intensity. Our results highlight how biodiversity can be vulnerable to factors, such as landscape fragmentation and habitat loss, that isolate local communities. PMID- 27555101 TI - Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids. AB - An investigation into the use of Lewis base catalysis for the enantioselective chlorolactonization of 1,2-disubstituted alkenoic acids is described. Two mechanistically distinct reaction pathways for catalytic chlorolactonization have been identified. Mechanistic investigation revealed that tertiary amines predominately operate as Bronsted rather than Lewis bases. Two potential modes of activation have been identified that involve donation of electron density of the carboxylate to the C?C bond as well hydrogen bonding to the chlorinating agent. Sulfur- and selenium-based additives operate under Lewis base catalysis; however, due to the instability of the intermediate benzylic chloriranium ion, chlorolactonization suffers from low chemo-, diastereo-, and enantioselectivities. Independent generation of the benzylic chloriranium ion shows that it is in equilibrium with an open cation, which leads to low specificities in the nucleophilic capture of the intermediate. PMID- 27555102 TI - The evolving role of international doctors in the Australian emergency medicine workforce. PMID- 27555103 TI - Effects of Race and Sex on Measured GFR: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: Kidney failure disproportionately affects older blacks versus whites. The reasons are unknown and may be related to lower measured glomerular filtration rate (GFR) and higher levels of albuminuria in community-based population samples. STUDY DESIGN: Cross-sectional analysis of a substudy of a prospective cohort. SETTING & PARTICIPANTS: Ancillary study following Multi Ethnic Study of Atherosclerosis (MESA) visit 5. PREDICTOR: Age, sex, and race. OUTCOMES & MEASUREMENTS: Measured GFR using plasma clearance of iohexol and urine albumin-creatinine ratio (ACR). RESULTS: GFR was measured in 294 participants. Mean age was 71+/-9 (SD) years, 47% were black, 48% were women, mean GFR was 73+/ 19mL/min/1.73m2, and median ACR was 10.0 (IQR, 5.8-20.9) mg/g. Measured GFR was on average 1.02 (95% CI, 0.79-1.24) mL/min/1.73m2 lower per year older. Mean GFR indexed for body surface area was not different between blacks versus whites (mean difference, 2.94 [95% CI, -1.37 to 7.26] mL/min/1.73m2), but was lower in women than men (mean difference, -9.34 [95% CI, -13.53 to -5.15] mL/min/1.73m2); this difference persisted and remained significant after adjustment for demographics, clinical characteristics, and measures of body size. The difference between men and women, but not between blacks and whites, was substantially greater when GFR was not indexed for body surface area. ACR was higher in older versus younger participants (mean difference, 3.2% [95% CI, 1.5%-4.8%] per year), but geometric mean ratio of ACR did not differ between blacks versus whites (mean difference, 19.7%; 95% CI, -39.1% to 6.1%) or between men versus women (mean difference, -4.4%; 95% CI, -27.7% to 26.3%). LIMITATIONS: This is a study of survivors. People who agreed to participate were younger than those who refused. CONCLUSIONS: In this first community-based study that included blacks and whites, no differences in measured GFR between races were found, suggesting that other factors must account for the disproportionately higher burden of kidney failure in older blacks versus whites. PMID- 27555104 TI - Honoring Patient Preferences: The 2016 National Kidney Foundation Presidential Address. PMID- 27555105 TI - Dialysis Patient Perspectives on CKD Advocacy: A Semistructured Interview Study. AB - BACKGROUND: Health advocacy groups provide education, raise public awareness, and engage in legislative, scientific, and regulatory processes to advance funding and treatments for many diseases. Despite a high burden of chronic kidney disease (CKD) in the United States, public awareness and research funding lag behind those for other disease states. We undertook this study of patients receiving maintenance dialysis to describe knowledge and beliefs about CKD advocacy, understand perceptions regarding advocacy participation, and elicit ideas for generating more advocacy in the dialysis community. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: 48 patients (89% response rate) receiving in center hemodialysis (n=39), home hemodialysis (n=4), and peritoneal dialysis (n=5) from 14 US states. METHODOLOGY: Semistructured interviews. ANALYTICAL APPROACH: Transcripts were thematically analyzed. RESULTS: 5 themes describing patient perspectives on CKD advocacy were identified: (1) advocacy awareness (advocacy vs engagement knowledge, concrete knowledge, CKD publicity), (2) willingness to participate (personal qualities, internal efficacy, external efficacy), (3) motivations (altruism, providing a purpose, advancement of personal health, self-education), (4) resource availability (time, financial and transportation, health status), and (5) mobilization experience (key figure, mobilization network). Participants displayed operational understanding of advocacy but generally lacked knowledge about specific opportunities for participation. Personal qualities and external efficacy were perceived as important for advocacy participation, as were motivating factors such as altruism and self-education. Resources factored heavily into perceived participation ability. Most participants identified a key figure who invited them to participate in advocacy. In-person patient-delivered communication about advocacy opportunities was identified as critical to enhancing CKD advocacy among patients living on dialysis therapy. LIMITATIONS: Potential selection bias and inclusion of only English-speaking participants may limit generalizability. CONCLUSIONS: Overall, our results suggest that there may be untapped advocacy potential within the dialysis community and highlight the need for local in-person patient-led initiatives to increase patient involvement in CKD advocacy. PMID- 27555107 TI - Intermediate and Long-term Outcomes of Survivors of Acute Kidney Injury Episodes: A Large Population-Based Cohort Study. AB - BACKGROUND: The long-term prognosis after acute kidney injury (AKI) is variable. It is unclear how the prognosis of AKI and its relationship to prognostic factors (baseline kidney function, AKI severity, prior AKI episodes, and recovery of kidney function) change as follow-up progresses. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The Grampian Laboratory Outcomes Morbidity and Mortality Study II (GLOMMS-II) is a large regional population cohort with complete serial biochemistry and outcome data capture through data linkage. From GLOMMS-II, we followed up 17,630 patients hospitalized in 2003 through to 2013. PREDICTORS: AKI identified using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine criteria, characterized by baseline kidney function (estimated glomerular filtration rate [eGFR] >= 60, 45-59, 30-44, and <30mL/min/1.73m2), AKI severity (KDIGO stage), 90-day recovery of kidney function, and prior AKI episodes. OUTCOMES: Intermediate- (30-364 days) and long term (1-10 years) mortality and long-term renal replacement therapy. MEASUREMENTS: Poisson regression in time discrete intervals. Multivariable Cox regression for those at risk in the intermediate and long term, adjusted for age, sex, baseline comorbid conditions, and acute admission circumstances. RESULTS: Of 17,630 patients followed up for a median of 9.0 years, 9,251 died. Estimated incidences of hospital AKI were 8.4% and 17.6% for baseline eGFRs>=60 and <60mL/min/1.73m2, respectively. Intermediate-term (30-364 days) adjusted mortality HRs for AKI versus no AKI were 2.48 (95% CI, 2.15-2.88), 2.50 (95% CI, 2.04-3.06), 1.90 (95% CI, 1.51-2.39), and 1.63 (95% CI, 1.20-2.22) for eGFRs>=60, 45 to 59, 30 to 44, and <30mL/min/1.73m2, respectively. Among 1-year survivors, long-term HRs were attenuated: 1.44 (95% CI, 1.31-1.58), 1.25 (95% CI, 1.09 1.43), 1.21 (95% CI, 1.03-1.42), and 1.08 (95% CI, 0.85-1.36), respectively. The excess long-term hazards in AKI were lower for lower baseline eGFRs (P for interaction = 0.01). LIMITATIONS: Nonprotocolized observational data. No adjustment for albuminuria. CONCLUSIONS: The prognostic importance of a discrete AKI episode lessens over time. Baseline kidney function is of greater long-term importance. PMID- 27555108 TI - The missing path to gain customers loyalty in pharmacy retail: The role of the store in developing satisfaction and trust. AB - BACKGROUND: An evolution led to community pharmacies experiencing increased competition both between themselves and with new entrants in the sector, for example, grocery retailers. Applying certain retail marketing strategies aimed at developing store loyalty may be an appropriate strategic path for pharmacies wanting to compete in this new arena. OBJECTIVES: This study aimed to develop and test a two-step model to identify the determinants of store loyalty for community pharmacies in Italy. METHODS: Based on the retail literature, qualitative research was conducted to identify key variables determining loyalty to community pharmacies. The model was then tested by means of a phone survey. A total of 735 usable questionnaires was collected. RESULTS: The study highlights the key role of the relationship between pharmacists and their customers in the loyalty building path; trust in pharmacists is the first driver of satisfaction and a direct and indirect (through satisfaction) driver of trust in pharmacies, which leads to store loyalty. Retail-level levers, such as the store environment, assortment, and communication, influence trust in pharmacies. CONCLUSIONS: This model is a first step toward investigating loyalty-building by applying the retail management literature's concepts to the community pharmacy sector. PMID- 27555106 TI - Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry. AB - BACKGROUND: The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries. FACTOR: Liver transplantation. OUTCOMES & MEASUREMENTS: Transplantation and patient survival. RESULTS: 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9% 100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4). LIMITATIONS: No data for liver disease of kidney therapy recipients. CONCLUSIONS: Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy. PMID- 27555109 TI - A Multimodal Structural and Functional Neuroimaging Study of Amnestic Mild Cognitive Impairment. AB - Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia. PMID- 27555110 TI - Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes. AB - OBJECTIVE: Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia. METHODS: The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset. RESULTS: Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia. CONCLUSION: Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk. PMID- 27555111 TI - Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients. AB - BACKGROUND: Acute mesenteric ischemia (AMI) has a high morbidity and mortality and often presents as a diagnostic challenge. Currently, there is no blood, urine, or radiologic tests that provide a definitive diagnosis of AMI. The aim of this study was to evaluate the clinical accuracy of urine intestinal fatty acid binding protein (I-FABP) to diagnosis AMI. MATERIALS AND METHODS: Twenty patients referred to the Acute Care Surgery service at University of Alberta Hospital with suspected AMI taken to the operating room for definitive diagnosis were recruited. Pathologic findings from surgical specimens confirmed a gold standard diagnosis for intestinal ischemia. The patients found to be nonischemic became the internal controls. Conventional clinical markers were examined in blood including white blood cell count, lactate, and creatinine. Blood was also examined by enzyme-linked immunosorbent assays (ELISAs) for I-FABP and interleukin-6. Urine was examined preoperatively and 6 and 24 h postoperatively for I-FABP. RESULTS: Thirteen patients were pathologically diagnosed with AMI while five patients were nonischemic; two were excluded due to missing biologic specimens. There was no difference in age or gender between ischemic and nonischemic patients (56 +/- 5 versus 66 +/- 11 years old, respectively; six females with ischemic and three females in the nonischemic group). There was no difference in serum lactate and creatinine between the two groups. Serum interleukin-6 levels in patients with AMI were significantly higher than nonischemic controls (0.4 +/- 0.2 ng/mL versus 0.2 +/- 0.07 ng/mL, respectively, P = 0.03). There was a nonstatistically significant increase in serum I-FABP in AMI patients compared to internal controls (9 +/- 3 ng/mL versus 2.4 +/- 0.9 ng/mL, respectively, P = 0.2). Urine I-FABP was significantly higher in patients diagnosed with AMI than in controls (7 +/- 1 ng/mL versus 2 +/- 1 ng/mL, respectively, P = 0.007). The receiver operating characteristic curve illustrated that urine I-FABP discriminates significantly between patients with AMI and controls (area under receiver operating characteristic = 0.88, P = 0.03). CONCLUSIONS: The traditional clinical markers lactate and white blood cell count were not able to differentiate AMI from nonischemic bowel. However, we found that urine I-FABP was a noninvasive biomarker with high specificity and sensitivity for accurately diagnosing AMI in patients. A noninvasive accurate tool for AMI would facilitate for a rapid treatment, while preventing unnecessary surgical interventions in high-risk patient populations. PMID- 27555114 TI - Pb2 BO3 Cl: A Tailor-Made Polar Lead Borate Chloride with Very Strong Second Harmonic Generation. AB - A meticulously designed, polar, non-centrosymmetric lead borate chloride, Pb2 BO3 Cl, was synthesized using KBe2 BO3 F2 (KBBF) as a model. Single-crystal X-ray diffraction revealed that the structure of Pb2 BO3 Cl consists of cationic [Pb2 (BO3 )](+) honeycomb layers and Cl(-) anions. Powder second harmonic generation (SHG) measurements on graded polycrystalline Pb2 BO3 Cl indicated that the title compound is phase-matchable (type I) and exhibits a remarkably strong SHG response, which is approximately nine times stronger than that of potassium dihydrogen phosphate, and the largest efficiency observed in materials with structures similar to KBBF. Further characterization suggested that the compound melts congruently at high temperature and has a wide transparency window from the near-UV to the mid-IR region. PMID- 27555112 TI - Lung Pericytes and Resident Fibroblasts: Busy Multitaskers. AB - Pericytes, resident fibroblasts, and mesenchymal stem cells are poorly described cell populations. They have recently been characterized in much greater detail in rodent lungs and have been shown to play important roles in development, homeostasis, response to injury and pathogens, as well as recovery from damage. These closely related mesenchymal cell populations form extensive connections to the lung's internal structure, as well as its internal and external surfaces. They generate and remodel extracellular matrix, coregulate the vasculature, help maintain and restore the epithelium, and act as sentries for the immune system. In this review, we revisit these functions in light of significant advances in characterizing and tracking lung fibroblast populations in rodents. Lineage tracing experiments have mapped the heritage, identified functions that discriminate lung pericytes from resident fibroblasts, identified a subset of mesenchymal stem cells, and shown these populations to be the predominant progenitors of pathological fibroblasts and myofibroblasts in lung diseases. These findings point to the importance of resident lung mesenchymal populations as therapeutic targets in acute lung injury as well as fibrotic and degenerative diseases. Far from being passive and quiescent, pericytes and resident fibroblasts are busily sensing and responding, through diverse mechanisms, to changes in lung health and function. PMID- 27555113 TI - Histone Deacetylase Inhibitor Vorinostat (SAHA) Suppresses IL-1beta-Induced Matrix Metallopeptidase-13 Expression by Inhibiting IL-6 in Osteoarthritis Chondrocyte. AB - Osteoarthritis (OA) is the most common whole-joint disease and is characterized by progressive loss of the cartilage matrix. Matrix metallopeptidase-13 (MMP-13) is a highly active and an abundantly expressed protease in OA cartilage and chondrocytes and degrades type II collagen and proteoglycans. We investigated the mechanism of MMP-13 suppression by histone deacetylase inhibitor vorinostat (SAHA). OA chondrocytes were obtained from knee cartilage after enzymatic digestion and treated with IL-1beta in the absence or presence of various histone deacetylase inhibitors. Gene expression was quantified using quantitative RT-PCR. Protein expression and chromatin modifications were determined by Western immunoblotting using specific antibodies. The effect of IL-6 on the expression of MMP-13 was determined by treating chondrocytes with recombinant IL-6 or by IL6 knockdown using IL6-specific siRNA. We found that SAHA is a potent suppressor of IL-1beta-induced MMP-13, tumor necrosis factor-alpha, and other catabolic marker expression in OA chondrocytes. Interestingly, SAHA rescued the COL2A1 and ACAN expression in OA chondrocytes that was down-regulated by IL-1beta. Of importance is our finding that IL-6-stimulated MMP-13 expression was independent of IL-1beta stimulation and was blocked by SAHA, suggesting that SAHA inhibits IL-6 signaling in OA chondrocytes. Taken together, our results suggest that SAHA could be used as a therapeutic agent for the management of OA. PMID- 27555115 TI - Antigen Receptor Nanoclusters: Small Units with Big Functions. AB - Adaptive lymphocytes express highly variable antigen receptors, allowing them to recognize a large variety of proteins, for example, derived from pathogens and tumor cells. Despite decades of investigations, the signaling mechanisms of these receptors are still incompletely understood. Super-resolution imaging studies revealed that antigen receptors, their coreceptors, and even some downstream signaling molecules tend to form dynamic nanometers-sized self-clusters in quiescent cells. Antigen stimulation induces the coalescence of these nanoclusters to form membrane proximal signalosomes that can mediate efficient signal transduction. In this review, we discuss the dynamic structures of T cell receptor and B cell receptor nanoclusters, the driving forces behind this spatial reorganization, as well as their potential relevance in the modulation of lymphocyte activation and function. PMID- 27555116 TI - A comparative study on the antioxidant effects of hesperidin and ellagic acid against skeletal muscle ischemia/reperfusion injury. AB - The antioxidant effects of ellagic acid (EA) and hesperidin (HES) against skeletal muscle ischemia/reperfusion injury (I/R) were performed. Hindlimb ischemia has been induced by tourniquet occlusion for 2 h on left hindlimb. At the end of ischemia, the tourniquate has been removed and initiated reperfusion for 2 h. EA (100 mg/kg) has been applied orally before ischemia/reperfusion in the EA + I/R group. HES (100 mg/kg) has been given orally in the HES + I/R group. The left gastrocnemius muscle has been harvested and stored immediately at -80 degrees C until assessed for the levels of MDA and antioxidant enzymes activities. MDA level has statistically increased in I/R group (p < 0.05) compared to other groups. The muscle tissue antioxidant enzymes activities were lower than the other groups in the I/R group (p < 0.05). EA and HES treatments significantly reversed the damage level in I/R, also activity of tissue SOD increased in the EA + I/R and HES + I/R groups. PMID- 27555117 TI - Increase in sensitivity of the baroreceptor reflex following microinjection of carbachol into the posterior hypothalamic nucleus of awake rats. AB - In a rat model, the baroreceptor reflex can be assessed by graded infusions of either phenylephrine or sodium nitroprusside with continuous hemodynamic monitoring. Microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) evokes an increase in mean arterial pressure and a change in heart rate. Lower doses of CCh evoke only tachycardia, whereas middle and higher doses evoke a biphasic change in heart rate of tachycardia followed by bradycardia. The bradycardia following the microinjection of CCh into the PHN can be attenuated by the previous administration of the vasopressin V1 receptor antagonist [d(CH2 )5 Tyr(Me)] arginine vasopressin (AVPX). Circulating arginine vasopressin (AVP) has been shown to increase the sensitivity of the baroreceptor reflex by stimulating vasopressin V1 receptors in the area postrema. The attenuation by AVPX of the bradycardia that results following the high doses of CCh suggests that AVP is released into the circulation following stimulation of cholinergic systems within the PHN. Thus, microinjection of a high dose of CCh (11 nmol) into the PHN alters the sensitivity of the baroreceptor reflex by increasing peripheral levels of AVP. PMID- 27555118 TI - Extended-hours hemodialysis is associated with lower mortality risk in patients with end-stage renal disease. AB - Extended-hours hemodialysis offers substantially longer treatment time compared to conventional hemodialysis schedules and is associated with improved fluid and electrolyte control and favorable cardiac remodeling. However, whether extended hours hemodialysis improves survival remains unclear. Therefore, we determined the association between extended-hours compared to conventional hemodialysis and the risk of all-cause mortality in a nationally representative cohort of patients initiating maintenance dialysis in the United States from 2007 to 2011. Survival analyses using causal inference modeling with marginal structural models were performed to compare mortality risk among 1206 individuals undergoing thrice weekly extended-hours hemodialysis or 111,707 patients receiving conventional hemodialysis treatments. The average treatment time per session for extended hours hemodialysis was 399 minutes compared to 211 minutes for conventional therapy. The crude mortality rate with extended-hours hemodialysis was 6.4 deaths per 100 patient-years compared with 14.7 deaths per 100 patient-years for conventional hemodialysis. In the primary analysis, patients treated with extended-hours hemodialysis had a 33% lower adjusted risk of death compared to those who were treated with a conventional regimen (95% confidence interval: 7% to 51%). Additional analyses accounting for analytical assumptions regarding exposure and outcome, facility-level confounders, and prior modality history were similar. Thus, in this large nationally representative cohort, treatment with extended-hours hemodialysis was associated with a lower risk for mortality compared to treatment with conventional in-center therapy. Adequately powered randomized clinical trials comparing extended-hours to conventional hemodialysis are required to confirm these findings. PMID- 27555119 TI - Label-free fluorescence lifetime and second harmonic generation imaging microscopy improves quantification of experimental renal fibrosis. AB - All forms of progressive renal diseases develop a final pathway of tubulointerstitial fibrosis and glomerulosclerosis. Renal fibrosis is usually quantified using histological staining, a process that is time-consuming and pathologist dependent. Here we develop a fast and operator-independent method to measure fibrosis utilizing the murine unilateral ureteral obstruction model which manifests a time-dependent fibrotic increase in obstructed kidneys while the contralateral kidneys are used as controls. After ureteral obstruction, kidneys were analyzed at 7, 14, and 21 days. Fibrosis was quantified using fluorescence lifetime imaging (FLIM) and second harmonic generation (SHG) in a Deep Imaging via Enhanced photon Recovery deep tissue imaging microscope. This microscope was developed for deep tissue along with second and third harmonic generation imaging and has extraordinary sensitivity toward harmonic generation. SHG data suggest the presence of more fibrillar collagen in the obstructed kidneys. The combination of short-wavelength FLIM and SHG analysis results in a robust assessment procedure independent of observer interpretation and let us create criteria to quantify the extent of fibrosis directly from the image. Thus, the FLIM-SHG technique shows remarkable improvement in quantification of renal fibrosis compared to standard histological techniques. PMID- 27555120 TI - Antiphospholipid syndrome and kidney disease. AB - The antiphospholipid syndrome is a common autoimmune disease caused by pathogenic antiphospholipid antibodies, leading to recurrent thrombosis and/or obstetrical complications. Importantly for nephrologists, antiphospholipid antibodies are associated with various renal manifestations including large renal vessel thrombosis, renal artery stenosis, and a constellation of intrarenal lesions that has been termed antiphospholipid nephropathy. This last condition associates various degrees of acute thrombotic microangiopathy, proliferative and fibrotic lesions of the intrarenal vessels, and ischemic modifications of the renal parenchyma. The course of the disease can range from indolent nephropathy to devastating acute renal failure. The pejorative impact of antiphospholipid antibody-related renal complication is well established in the context of systemic lupus erythematous or after renal transplantation. In contrast, the exact significance of isolated antiphospholipid nephropathy remains uncertain. The evidence to guide management of the renal complications of antiphospholipid syndrome is limited. However, the recent recognition of the heterogeneous molecular mechanisms underlying the progression of intrarenal vascular lesions in antiphospholipid syndrome have opened promising tracks for patient monitoring and targeted therapeutic intervention. PMID- 27555122 TI - A new validated HPLC method for the determination of quercetin: Application to study pharmacokinetics in rats. AB - A simple, accurate, and reproducible high-performance liquid chromatography (HPLC) method has been developed and validated for the quantification of quercetin (QR) in rat plasma. The method involves a simple protein precipitation procedure to extract both QR and thymoquinone (TQ), the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20 A HPLC system equipped with a Supelcosil LC-18 T C18 column and an isocratic mobile phase consisting of 0.3% trichloroacetic acid in water and acetonitrile HPLC-grade (50:50, v/v) run at a flow rate of 0.9 mL/min for 13 min. The UV detection wavelength was set at 254 nm. The method exhibited good linearity (R2 > 0.994) over the assayed concentration range (0.10-25 MUg/mL) and demonstrated good intra-day and inter day precision and accuracy (relative standard deviations and the deviation from predicted values were <20%). This method was also successfully applied for studying the pharmacokinetics of QR in rats following a single oral dose of QR to evaluate its pharmacokinetic parameters in rats. PMID- 27555121 TI - Twenty years of evolving trends in racial disparities for adult kidney transplant recipients. AB - Disparities in outcomes for African American (AA) kidney transplant recipients have persisted for 40 years without a comprehensive analysis of evolving trends in the risks associated with this disparity. Here we analyzed U.S. transplant registry data, which included adult Caucasian or AA solitary kidney recipients undergoing transplantation between 1990 and 2009 comprising 202,085 transplantations. During this 20-year period, the estimated rate of 5-year graft loss decreased from 27.6% to 12.8%. Notable trends in baseline characteristics that significantly differed by race over time included the following: increased prevalence of diabetes from 2001 to 2009 in AAs (5-year slope difference: 3.4%), longer time on the waiting list (76.5 more days per 5 years in AAs), fewer living donors in AAs from 2003 to 2009 (5-year slope difference: -3.36%), more circulatory death donors in AAs from 2000-09 (5-year slope difference: 1.78%), and a slower decline in delayed graft function in AAs (5-year slope difference: 0.85%). The absolute risk difference between AAs and Caucasians for 5-year graft loss significantly declined over time (-0.92% decrease per 5 years), whereas the relative risk difference actually significantly increased (3.4% increase per 5 years). These results provide a mixed picture of both promising and concerning trends in disparities for AA kidney transplant recipients. Thus, although the disparity for graft loss has significantly improved, equity is still far off, and other disparities, including living donation rates and delayed graft function rates, have widened during this time. PMID- 27555123 TI - Room-Temperature and Aqueous-Phase Synthesis of Plasmonic Molybdenum Oxide Nanoparticles for Visible-Light-Enhanced Hydrogen Generation. AB - A straightforward aqueous synthesis of MoO3-x nanoparticles at room temperature was developed by using (NH4 )6 Mo7 O24 ?4 H2 O and MoCl5 as precursors in the absence of reductants, inert gas, and organic solvents. SEM and TEM images indicate the as-prepared products are nanoparticles with diameters of 90-180 nm. The diffuse reflectance UV-visible-near-IR spectra of the samples indicate localized surface plasmon resonance (LSPR) properties generated by the introduction of oxygen vacancies. Owing to its strong plasmonic absorption in the visible-light and near-infrared region, such nanostructures exhibit an enhancement of activity toward visible-light catalytic hydrogen generation. MoO3 x nanoparticles synthesized with a molar ratio of Mo(VI) /Mo(V) 1:1 show the highest yield of H2 evolution. The cycling catalytic performance has been investigated to indicate the structural and chemical stability of the as-prepared plasmonic MoO3-x nanoparticles, which reveals its potential application in visible-light catalytic hydrogen production. PMID- 27555124 TI - The use of sugammadex in a pregnant patient with Wolff-Parkinson-White syndrome. AB - Wolff-Parkinson-White (WPW) syndrome is a rare pre-excitation syndrome which develops when atrioventricular conduction occurs through a pathologic accessory pathway known as the bundle of Kent instead of atrioventricular node, hence resulting in tachycardia. Patients with WPW syndrome may experience various symptoms arising from mild-to-moderate chest disease, palpitations, hypotension, and severe cardiopulmonary dysfunction. These patients are most often symptomatic because of cardiac arrhythmias. In this case report, we present an uneventful anesthetic management of a pregnant patient with WPW syndrome undergoing cesarean delivery. A 23-year-old American Society of Anesthesiologists class 2 pregnant patient was diagnosed with WPW syndrome. Her preoperative 12-lead electrocardiogram showed a sinus rhythm at 82 beats per minute, a delta wave, and a short PR interval. After an uneventful surgery, sugammadex 2mg/kg was administered as a reversal agent instead of neostigmine. Then she was discharged to her obstetrics service. Serious hemodynamic disorders may occur in patients with WPW syndrome due to development of fatal arrhythmias. Neostigmine used as a reversal agent in general anesthesia can trigger such fatal arrhythmias by leading changes in cardiac conduction. We believe that sugammadex, which is safely used in many areas in the scope of clinical practice, can be also used for patients diagnosed with WPW syndrome. PMID- 27555125 TI - Assessing student usage, perception, and the utility of a Web-based simulation in a third-year medical school clerkship. AB - STUDY OBJECTIVE: The goals of this study were to assess students' usage data of Web-based simulation (WBS), to determine if it can fill gaps in clinical experience-based medical education, and to determine students' perceived value of this kind of simulation during a clinical clerkship. DESIGN: Observational/prospective cohort. SETTING: Medical school affiliated with a large academic hospital. SUBJECTS: A total od 138 medical students. INTERVENTIONS: Web based simulation. MEASUREMENTS: Medical students in an anesthesiology clerkship were assigned a WBS focusing on the clinical use of pulmonary artery catheters (PACs). Usage data, including day of week and time of day that the simulation was used and total usage time, were collected for 99 students. Eighty voluntary survey responses, which gauged student perception of the simulation and clinical exposure to PACs, were also collected. MAIN RESULTS: Seventy-two percent of attempts were made during nonclinical hours of 5 pm to 7 am. Seventy-seven percent of students spent less than 30 minutes in total using the simulation. Students preferred the simulation (rated 4.1/5) over textbook (3.59) learning to a statistically significant degree (P < .001) and held favorable views toward the simulation. Sixty-seven percent of students had never encountered a patient with a PAC before performing the simulation, and 41% did not discuss this learning objective during their clerkship. Students' self-rated understanding of PACs significantly increased from a presimulation score of 1.8 of 5, to 2.56 (mean difference, 0.760; P < .001) after using the simulation. CONCLUSIONS: WBS in medical school clerkships is accepted by students and can fill gaps in clinical medical school education, without negatively affecting students' workloads or clerkship experiences. PMID- 27555126 TI - Recovery of laryngeal nerve function with sugammadex after rocuronium-induced profound neuromuscular block. AB - STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy of sugammadex in reversing profound rocuronium-induced neuromuscular block at the laryngeal adductor muscles using motor-evoked potentials (mMEPs). DESIGN: A prospective observational study. SETTING: University surgical center. PATIENTS: Twenty patients with American Society of Anesthesiologists physical class I-II status who underwent propofol-remifentanil anesthesia for the surgery of the thyroid gland. INTERVENTIONS: Patients were enrolled for reversal of profound neuromuscular block (sugammadex 16 mg/kg, 3 minutes after rocuronium 1.2 mg/kg). To prevent laryngeal nerve injury during the surgical procedures, all patients underwent neurophysiologic monitoring using mMEPs from vocal muscles. At the same time, the registration of TOF-Watch acceleromyograph at the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio >=0.9. MEASUREMENT AND MAIN RESULTS: After injection of 16 mg/kg of sugammadex, the mean time to recovery of the basal mMEPs response at the laryngeal adductor muscles was 70 +/- 18.2 seconds. The mean time to recovery of the TOF ratio to 0.9 was 118 +/- 80 seconds. In the postoperative period, 12 patients received follow-up evaluation of the vocal cords and no lesions caused by the surface laryngeal electrode during electrophysiological monitoring were noted. CONCLUSIONS: Recovery from profound rocuronium-induced block on the larynx is fast and complete with sugammadex. In urgent scenarios, "early" extubation can be performed, even with a TOF ratio <=0.9. However, all procedures to prevent postoperative residual curarization should still be immediately undertaken. PMID- 27555127 TI - Does the perioperative analgesic/anesthetic regimen influence the prevalence of long-term chronic pain after mastectomy? AB - STUDY OBJECTIVE: To investigate if the anesthetic/analgesic regimen is associated with the risk of reporting long-term chronic postmastectomy pain (CPMP). DESIGN: Cross-sectional survey SETTING: Academic hospital PATIENTS: A total of 267 women having undergone mastectomy with axillary lymph node dissection between 2003 and 2008 INTERVENTIONS: All patients were contacted between October and December 2012, with a questionnaire asking for persistent pain after surgery and its characteristics. MEASUREMENTS: Besides demographical data, tumor characteristics, and adjuvant treatment, we recorded type and doses of intraoperative anesthetics/analgesics (sufentanil, ketamine, clonidine, nonsteroidal anti inflammatory drugs, MgSO4, propofol, or halogenated agents). RESULTS: Of the 128 patients returning analyzable questionnaires, 43.8% reported chronic pain (48.2% with neuropathic characteristics). Multivariate logistic/linear regression model showed 4 factors independently associated with persistent pain: recall of preoperative pain (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.09 1.48), chemotherapy (OR, 1.32; 95% CI, 1.13-1.55), need for strong opioids in postanesthesia care unit (OR, 1.30; 95% CI, 1.11-1.53), and halogenated agent anesthesia (OR, 0.81; 95% CI, 0.70-0.95). CONCLUSION: In conclusion, our study confirms the high prevalence of CPMP, 4 to 9 years after surgery. Recall of preoperative pain, chemotherapy, and need for strong opioids in the postanesthesia care unit were all associated with the presence of chronic pain. Of the intraoperative analgesics/anesthetics studied, only use of halogenated agents was associated with a lower prevalence of CPMP. PMID- 27555128 TI - Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series. AB - STUDY OBJECTIVE: Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. DESIGN: Case series, chart review. SETTING: Academic medical center. PATIENTS: Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. INTERVENTIONS: The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. MEASUREMENTS: Patient charts were reviewed for any evidence of complications or reduced block efficacy. MAIN RESULTS: A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. CONCLUSIONS: This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. PMID- 27555129 TI - Middle cerebral artery blood flow velocity during beach chair position for shoulder surgery under general anesthesia. AB - OBJECTIVES: The goal of the present study was to examine changes of middle cerebral artery (VMCA) blood flow velocity in patients scheduled for shoulder surgery in beach chair position. DESIGN: Prospective observational study. SETTING: Operating room, shoulder surgery. PATIENTS: Fifty-three consecutive patients scheduled for shoulder surgery in beach chair position. INTERVENTIONS: Transcranial Doppler performed after induction of general anesthesia (baseline), after beach chair positioning (BC1), during surgery 20minutes (BC2), and after back to supine position before stopping anesthesia (supine). MEASUREMENTS: Mean arterial pressure (MAP), end-tidal CO2, and volatile anesthetic concentration and VMCA were recorded at baseline, BC1, BC2, and supine. Postoperative neurologic complications were searched. MAIN RESULTS: Beach chair position induced decrease in MAP (baseline: 73+/-10mm Hg vs lower MAP recorded: 61+/-10mm Hg; P<.0001) requiring vasopressors and fluid challenge in 44 patients (83%). There was a significant decrease in VMCA after beach chair positioning (BC1: 33+/-10cm/s vs baseline: 39+/-14cm/s; P=.001). The VMCA at baseline (39+/-2cm/s), BC2 (35+/ 14cm/s), and supine (39+/-14cm/s) were not different. The minimal alveolar concentration of volatile anesthetics, end-tidal CO2, SpO2, and MAP were not different at baseline, BC1, BC2, and supine. CONCLUSION: Beach chair position resulted in transient decrease in MAP requiring fluid challenge and vasopressors and a moderate decrease in VMCA. PMID- 27555130 TI - Correlation between extraction force during tracheal intubation stylet removal and postoperative sore throat. AB - STUDY OBJECTIVE: To examine postoperative sore throat resulting from tracheal intubation stylet removal. DESIGN: Prospective cohort study. SETTING: Operating rooms and hospital ward. PATIENTS: A total of 50 American Society of Anesthesiologists physical status 1 and 2 patients who underwent elective abdominal and/or orthopedic surgery under general anesthesia. INTERVENTIONS: Patients were allocated to 2 groups: those who developed sore throat postoperatively (ST group) and those who did not (NST group). Comparative analysis of these 2 groups was performed to identify risk factors of the development of sore throat. MEASUREMENTS: The extraction force during stylet removal was measured using a force measuring device. Postoperative sore throat was assessed by an anesthesiologist. MAIN RESULTS: Nine patients (18%) complained of postoperative sore throat. Increased extraction force (P=.0054; odds ratio, 1.84; 95% confidence interval, 1.20-2.84) was the only significant risk factor for the development of postoperative sore throat. An extraction force of >10.3N was determined as a cutoff for developing postoperative sore throat. CONCLUSION: Postoperative sore throat was significantly related to increased extraction force during stylet removal. PMID- 27555131 TI - Flexible optical intubation via the Ambu Aura-i vs blind intubation via the single-use LMA Fastrach: a prospective randomized clinical trial. AB - STUDY OBJECTIVE: This study was designed to compare the Ambu Aura-i to the single use LMA Fastrach regarding time to intubation, success rate, and airway morbidity in patients undergoing elective surgery requiring general anesthesia. DESIGN: Prospective, randomized controlled trial. SETTING: Academic medical center. PATIENTS: Sixty-five adult patients scheduled for elective surgery requiring general anesthesia. INTERVENTIONS: Patients were randomized into 2 groups. Group A (n=33) were intubated using Ambu Aura-i and the Ambu aScope 2, a disposable flexible intubating scope, whereas those in group B (n=33) were blindly intubated using the Intubating Laryngeal Mask Airway (ILMA). MEASUREMENTS: First-attempt intubation success rate, overall intubation success rate, time to intubation, incidence of airway morbidity. MAIN RESULTS: The data demonstrated that time for endotracheal intubation in the ILMA group was significantly shorter than in the Ambu Aura-i group (P<.05). There was no difference in the first-attempt intubation success rate (Aura-i=26/33, 78.8%; ILMA=27/33, 81.8%; P=.757) or the overall intubation success rate (Aura-i=29/33, 87.9%; ILMA=31/33, 93.9%; P=.392) between the groups. Four patients (12%) in the Ambu Aura-i group had a failed intubation; 1 was due to a failure of the aScope monitor, whereas 3 were due to inability to visualize the glottis. Two patients (7%) in the ILMA group had a failed intubation due to esophageal intubation. There was no statistically significant difference in airway morbidity between the 2 groups. CONCLUSIONS: The data suggest that intubation with the ILMA is faster but that first-attempt and overall intubation success rates were comparable in both groups. The results suggest that although the flexible intubating scope-guided Aura-i does not outperform blind intubation via the ILMA, the technique is comparable in terms of first-attempt and overall intubation success rate. PMID- 27555132 TI - Two loose screws: near-miss fall of a morbidly obese patient after an operating room table failure. AB - Operating room surgical table failure is a rare event but can lead to a dangerous situation when it does occur. The dangers can be compounded in the presence of obesity, especially in the anesthetized or sedated patient. We present a case of a near-miss fall of a morbidly obese patient while turning the patient in preparation to transfer from the operating room table to the hospital bed when 2 fractured bolts in the tilt cylinder mechanism led to an operating room table failure. PMID- 27555133 TI - Preoperative paracetamol improves post-cesarean delivery pain management: a prospective, randomized, double-blind, placebo-controlled trial. AB - STUDY OBJECTIVE: To evaluate the analgesic effect of preoperative single dose intravenous paracetamol on postoperative pain and analgesic consumption within 24hours after elective cesarean surgery. DESIGN: Prospective, randomized, double blind, placebo-controlled clinical trial. SETTING: University Teaching Hospital. PATIENTS: American Society of Anesthesiologists (ASA) I and II 60 patients between 18-40years of age who were scheduled to undergo elective cesarean section. INTERVENTIONS: Patients were randomized into two groups to receive either intravenous 1g paracetamol (100mL) (Group P) or 0.9% NaCl solution (100mL) (Group C) 15minutes before the induction of general anesthesia. After delivery of newborn 0.15mg kg(-1) morphine was administered to all patients in both groups. Postoperative analgesia was provided with patient-controlled intravenous analgesia with morphine in the postoperative period. MEASUREMENTS: Pain which is the primary outcome measure was assessed at 15th, 30th minutes and 1st, 2nd, 4th, 6th, 12th, 24th hours by the Visual Analogue Scale. Patients' demographics, hemodynamics, Apgar score, additional analgesic requirement, side effects, patients' satisfaction and postoperative total morphine consumption within 24hours were recorded. MAIN RESULTS: Median visual analogue scale for pain in Group P was significantly lower compared to Group C at all time points except for the score at 24th h postoperatively (P<.05). Additional analgesic requirement during postoperative first hour was lower in Group P (P<.05). Total morphine consumption was higher in Group C compared with Group P (P<.05). There was no difference between groups with respect to Apgar scores, side effects, and patient satisfaction (P>.05). CONCLUSIONS: Preoperative use of single-dose intravenous 1g paracetamol was found to be effective in reducing the severity of pain and opioid requirements within 24hours after cesarean section. PMID- 27555134 TI - Complete heart block in pregnancy: case report, analysis, and review of anesthetic management. AB - Maternal complete heart block can pose significant challenges for the anesthesiologist in the antepartum, peripartum, and postpartum periods. Some patients may present for the first time in the puerperium with dizziness, weakness, syncope, or congestive heart failure as a result of the additional hemodynamic burden that accompanies pregnancy. Although there is an increase in permanent pacemaker placement in young symptomatic patients before pregnancy, prophylactic placement of pacemakers in asymptomatic parturients is not always indicated. The need for temporary or permanent pacemakers in asymptomatic women should be assessed on a case-by-case basis; many of these patients may be safely managed during labor and delivery without pacing. The parturient with complete heart block must be followed vigilantly during pregnancy and post delivery, as the need for pacemaker insertion can also arise in the postpartum period. We present a case of third-degree heart block in a 26-year-old parturient. PMID- 27555135 TI - Airway risk factors for the Miller laryngoscope blade. AB - STUDY OBJECTIVE: The purpose of this study was to analyze previously reported airway risk factors in the performance of Miller laryngoscopy and orotracheal intubation. DESIGN: Prospective, observational study. SETTING: Operating rooms. PATIENTS: A total of 978 American Society of Anesthesiologists I-III adults requiring general orotracheal anesthesia for elective surgery. INTERVENTIONS: None. MEASUREMENTS: Nine previously reported airway risk factors used in predicting difficult laryngoscopy, modified McCormack-Lehane views observed during initial unaided Miller blade laryngoscopy, and number of attempts or need for alternate airway tools to facilitate orotracheal intubation. MAIN RESULTS: Orotracheal intubation occurred in 941 of 978 (96.2%) patients with the Miller blade, although 8 patients required 3 attempts, with the remaining 37 patients requiring alternate airway tools. There were no failed orotracheal intubations. Multivariable analysis revealed that modified Mallampati class, thyromental distance, and ability to prognath were associated with progressively inferior modified Cormack-Lehane views, whereas modified Mallampati class, height, and head and neck extension were associated with progressive difficulty with orotracheal intubation. CONCLUSIONS: The Miller blade is highly successful in the performance of direct laryngoscopy for orotracheal intubation. These findings suggest that different sets of airway risk factors affect the process of laryngoscopy and orotracheal intubation. PMID- 27555136 TI - Combined preoperative femoral and sciatic nerve blockade improves analgesia after anterior cruciate ligament reconstruction: a randomized controlled clinical trial. AB - STUDY OBJECTIVE: To compare preoperative femoral (FNB) with combined femoral and sciatic nerve block (CFSNB) in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction. DESIGN: Prospective, randomized clinical trial. SETTING: Ambulatory surgery center affiliated with an academic medical center. PATIENTS: Sixty-eight American Society of Anesthesiology physical status I and II patients undergoing arthroscopic ACL reconstruction. INTERVENTIONS: Subjects randomized to the CFSNB group received combined femoral and sciatic nerve blocks preoperatively, whereas patients randomized to the FNB group only received femoral nerve block preoperatively. Both groups then received a standardized general anesthetic with a propofol induction followed by sevoflurane or desflurane maintenance. Intraoperative pain was treated with fentanyl. Pain in the postanesthesia care unit (PACU) was treated with ketorolac and opiates. Patients with significant pain despite ketorolac and opiates could receive a rescue nerve block. MEASUREMENTS: Our primary outcome variable was highest Numeric Rating Scale (NRS) pain score in PACU. NRS pain scores, opioid consumption, opioid adverse effects, and patient satisfaction were assessed perioperatively until postoperative day 3. MAIN RESULTS: The highest PACU NRS pain score was significantly higher in the FNB group compared with the CFSNB group (7 [3-10] vs 5 [0-10], P=.002). The FNB group required significantly larger doses of opioids perioperatively (31.8 vs 19.8mg intravenous morphine equivalents, P<.001). PACU length of stay was significantly longer in the FNB group (128.2 vs 103.1minutes, P=.006). There was no significant difference in opioid consumption, pain scores, or patient satisfaction on postoperative days 1 3 between groups. CONCLUSIONS: Preoperative CFSNB for arthroscopic ACL reconstruction improves analgesia, decreases opioid consumption perioperatively, and decreases PACU length of stay when compared with FNB alone. PMID- 27555138 TI - Sevoflurane-associated torsade de pointes in a patient with congenital long QT syndrome genotype 2. AB - Although patients with congenital long QT syndrome (c-LQTS) are considered to be at high risk for anesthesia, few reports describe c-LQTS genotype-specific considerations for anesthesia. We describe a case of torsade de pointes (TdP) caused by sevoflurane in a patient with c-LQTS genotype 2 (LQT2). A 39-year-old woman diagnosed with c-LQTS was scheduled for an elective therapeutic abortion. Immediately after starting the operation, the patient developed TdP. Since pulseless ventricular tachycardia was sustained despite intravenous injection of lidocaine, defibrillation was performed. Analysis of the electrocardiogram revealed that the corrected QT interval before anesthesia was 530 ms and 2.0% sevoflurane markedly prolonged the corrected QT interval to 693 ms. Postoperative studies revealed a mutation in the KCNH2 gene. Anesthesiologists should note that patients with LQT2 could be more susceptible to volatile anesthetics than are those with other major genotypes. Genotype-specific management of anesthesia may reduce the risk of developing TdP during the perioperative period. PMID- 27555137 TI - Levobupivacaine vs racemic bupivacaine in spinal anesthesia for sequential bilateral total knee arthroplasty: a retrospective cohort study. AB - STUDY OBJECTIVES: To compare the anesthetic potency and safety of spinal anesthesia with higher dosages of levobupivacaine and bupivacaine in patients for bilateral sequential for total knee arthroplasty (TKA). DESIGN: Retrospective cohort study. SETTING: Operation theater with postoperative inpatient follow-up. PATIENTS: The medical records of 315 patients who underwent sequential bilateral TKA were reviewed. INTERVENTIONS: Patients who received intrathecal levobupicavaine 0.5% were compared with patients who received hyperbaric bupivacaine 0.5% with fentanyl 25 MUg for spinal anesthesia. MEASUREMENTS: The primary outcome was the use of rescue analgesia (systemic opioids, conversion to general anesthesia) during surgery for both groups. Secondary outcomes included adverse effects of local anesthetics (hypotension and bradycardia) during surgery and morbidity related to spinal anesthesia (postoperative nausea, vomiting, and bleeding) during hospital stay. MAIN RESULTS: One hundred fifty patients who received intrathecal levobupivacaine 0.5% (group L) were compared with 90 patients given hyperbaric bupivacaine 0.5% with fentanyl 25 MUg (group B). The mean volume of levobupivacaine administered was 5.8 mL (range, 5.0-6.0 mL), and that of bupivacaine was 3.8 mL (range, 3.5-4.0 mL). Both groups achieved similar maximal sensory level of block (T6). The time to maximal height of sensory block was significantly shorter in group B than group L, 18.2 +/- 4.5 vs 23.9 +/- 3.8 minutes (P< .001). The time to motor block of Bromage 3 was also shorter in group B (8.7 +/- 4.1 minutes) than group L (16.0 +/- 4.5 minutes) (P< .001). Patients in group B required more anesthetic supplement than group L (P< .001). Hypotension and postoperative bleeding were significantly less common in group L than group B. CONCLUSION: Levobupivacaine at a higher dosage provided longer duration of spinal anesthesia with better safety profile in sequential bilateral TKA. PMID- 27555139 TI - A validation study of the intubation difficulty scale for obese patients. AB - STUDY OBJECTIVE: An intubation difficulty scale (IDS) is the most commonly used tool to pronounce difficult intubation among obese patients in research area. There have not been any studies on assessing the use of IDS. The objectives were to determine the performance of the IDS among obese patients to define difficult tracheal intubation (DI) according to the subjective assessment of the difficulty experienced and to identify their optimal cutoff points. DESIGN: Cross-sectional study. SETTING: Tertiary care hospital. PATIENTS: Adult obese Thai patients who underwent conventional endotracheal intubation. MEASUREMENTS: Data of subjective assessment of the difficulty experienced by category-easy, somewhat difficult, and difficult-were collected from experienced anesthetic personnel who performed endotracheal intubation. IDS scores were collected by research assistants. MAIN RESULTS: There were 552 obese patients recruited. The incidence of somewhat DI was 14.3% and that of DI was 2.2%. The overall performance of the IDS using area under the receiver operating characteristic curves of somewhat DI is 0.99 with 95% confidence interval (CI) of 0.98 and 0.99 and that of DI is 1 (95% confidence interval, 1-1). For somewhat DI, the optimal cutoff point is 2; it provides sensitivity and specificity of 100% and 92%. The IDS scores of 5 indicate DI which had sensitivity and specificity of 100% and 100%. CONCLUSIONS: The IDS remains a good tool to declare DI among obese patients. It is recommended that a score of 2 or higher is an optimal cutoff point to indicate somewhat DI and a score of 5 or higher is an optimal cutoff point to indicate DI. PMID- 27555140 TI - Influence of dexmedetomidine on cognitive function in volunteers. AB - STUDY OBJECTIVE: Some outpatient procedures are performed under sedation with dexmedetomidine, although the effect of dexmedetomidine on cognitive function remains unclear. This study investigated the effect of dexmedetomidine on cognitive function in healthy volunteers. DESIGN: Observation study in volunteers. SETTING: University-affiliated teaching hospital. PATIENTS: Six healthy volunteers. INTERVENTIONS: After infusion of a 6-MUg/kg per hour loading dose of dexmedetomidine for 10 minutes, a maintenance infusion of 0.4 MUg/kg per hour was administered for 4 hours. MEASUREMENTS: Cognitive function was evaluated before infusion (baseline) and at 2, 4, 6, and 8 hours after infusion. Cognitive function, response speed, accuracy, and consistency were measured by CogHealth. Depth of sedation was evaluated at 1-hour intervals by evaluating the Bispectral Index. Data are presented as the change from baseline. MAIN RESULTS: The Bispectral Index value was significantly lower from 10 minutes to 6 hours after infusion versus the pre-infusion value. Response speed was also significantly lower at 2 hours and 4 hours after infusion (92 +/- 8%, P< .0001; 93 +/- 6%, P< .0001), as was consistency (96 +/- 7%, P= .0009; 96 +/- 5%, P= .0003). Response accuracy was unaltered by the infusion. CONCLUSIONS: Dexmedetomidine slightly reduced response speed and consistency, but did not affect response accuracy. Cognitive function was restored to pre-administration values 2 hours after the infusion of dexmedetomidine was discontinued. PMID- 27555141 TI - Increasing body mass index and the incidence of intraoperative hypoxemia. AB - STUDY OBJECTIVE: Obese patients regularly present for surgery and have greater hypoxemia risk. This study aimed to identify the risk and incidence of intraoperative hypoxemia with increasing body mass index (BMI). DESIGN: This was a retrospective cohort study. SETTING: Operating room. PATIENTS: A total of 15,238 adult patients who underwent general anesthesia for elective noncardiac surgery at a single large urban academic institution between January 2013 and December 2014. INTERVENTIONS: Unadjusted and risk-adjusted logistic regression analyses explored the relationship between increasing categories of BMI and intraoperative hypoxemia, severe hypoxemia, and prolonged hypoxemia. MEASUREMENTS: Intraoperative pulse oximeter readings and preoperative patient characteristics. MAIN RESULTS: With normal BMI, 731 (16%) patients experienced hypoxemia compared with 1150 (28%) obese patients. Adjusted odds ratio (AOR) of intraoperative hypoxemia increased with each category of BMI from 1.27 (95% confidence interval [CI], 1.12-1.44) in overweight patients to 2.63 (95% CI, 2.15 3.23) in patients with class III obesity. AOR of severe hypoxemia was significant with class I obesity (AOR, 1.32; 95% CI, 1.08-1.60), class II obesity (AOR, 2.01; 95% CI, 1.59-2.81), and class III obesity (AOR, 2.27; 95% CI, 1.75-2.93). AOR of prolonged hypoxemia increased with BMI from 3.29 (95% CI, 1.79-6.23) with class I obesity to 9.20 (95% CI, 4.74-18) with class III obesity. CONCLUSIONS: Despite existing practices to limit hypoxemia in obese patients, the odds of experiencing intraoperative hypoxemia increase significantly with increasing categories of BMI. Further practices may need to be developed to minimize the risk of intraoperative hypoxemia in obese patients. PMID- 27555142 TI - An update on predictive biomarkers for major adverse cardiovascular events in patients undergoing vascular surgery. AB - Cardiovascular complications signify a major cause of morbidity and mortality in patients undergoing vascular surgery adversely affecting both short- and long term prognosis. During the last decade, unmet needs for a distinct cardiovascular risk assessment have led to an intensive research for establishment of biomarkers with sufficient predictive value. This literature review aims in examining the value of several biomarkers in predicting the incidence of major adverse cardiac events in vascular surgery patients. We reviewed the English language literature and analyzed the biomarkers as independent predictors or in correlation with other factors. We found several biomarkers showing a significant predictive value for a major adverse cardiovascular event in patients undergoing vascular surgery. These biomarkers can be used in clinical practice as outcome predictors, although sensitivity and specificity varies. Detection of subclinical cardiovascular damage may improve total risk estimation and facilitate clinical assessment of patients at risk for future cardiovascular events. The wide variety of sensitivity and specificity in predicting a MACE of these biomarkers exert the need for future trials in which these markers will be tested as adjunctive tools of cardiovascular risk estimation scoring systems. PMID- 27555143 TI - Casting early light on anesthesiology milestone validation. PMID- 27555144 TI - Prone position craniotomy in pregnancy without fetal heart rate monitoring. AB - A pregnant patient in second trimester scheduled for posterior fossa craniotomy in prone position is a challenge for the anesthesiologist. Things to consider are physiological changes during pregnancy, non-obstetric surgery in pregnant patients, neuroanesthetic principles, effects of prone positioning, and need for fetal heart rate (FHR) monitoring. We have described the anesthetic management of this case and discussed intra-operative FHR monitoring including controversies about its role, indications, and various options available as per fetal gestational age. In our case we attempted intermittent intra-operative FHR monitoring to optimize maternal positioning and fetal oxygenation even though the fetus was pre-viable. However the attempt was abandoned due to practical difficulties with prone positioning. Patient made good neurological recovery following the procedure and delivered a healthy term baby 4 months later. Decisions regarding fetal monitoring should be individualized based on viability of the fetus and feasibility of emergency cesarean delivery. Good communication between a multidisciplinary team involving neurosurgeon, anesthesiologist, obstetrician, and neonatologist is important for a successful outcome for mother and fetus. We conclude that prone position neurosurgery can safely be carried out in a pregnant patient with pre-viable fetus without FHR monitoring. PMID- 27555145 TI - Association between preoperative maternal anxiety and neonatal outcomes: a prospective observational study. AB - STUDY OBJECTIVE: Preoperative anxiety can be associated with poor postoperative clinical outcomes. We aimed to assess whether preoperative maternal anxiety level of obstetric patients scheduled for elective cesarean surgery has an effect on clinical outcome of the newborn. DESIGN: A prospective observational study. SETTING: Operating room. PATIENTS: Sixty pregnant women with American Society of Anesthesiologists physical status 1 and 2 scheduled for elective cesarean surgery were enrolled. INTERVENTIONS: All patients received spinal anesthesia with hyperbaric bupivacaine 12.5mg. MEASUREMENTS: We performed a State-Trait Anxiety Inventory questionnaire to evaluate preoperative maternal anxiety. We used the Apgar scoring system to assess the physical condition of the newborn. Hemodynamic measurements (heart rate, systolic and diastolic blood pressure) were recorded at baseline, skin incision, childbirth, and 10, 15, and 30minutes after skin incision. The use of ephedrine, nausea, and vomiting were recorded as well. MAIN RESULTS: Average preoperative maternal state anxiety score was 41.1+/-4.6, and trait anxiety score was 50.9+/-5.7. Average Apgar scores of newborns were 7.6+/ 0.8 and 9.2+/-0.6, at first minute and fifth minute, respectively. We found no significant relationship between the anxiety scores and Apgar scores at first and fifth minute. Forty-two patients required ephedrine, 5 patients had nausea, and 5 patients had vomiting. CONCLUSIONS: We concluded that there was no relationship between preoperative maternal anxiety scores and Apgar scores at the first and fifth minute. PMID- 27555146 TI - Ultrashort acting remifentanil is not superior to long-acting sufentanil in preserving cognitive function-a randomized study. AB - STUDY OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a well-known complication after cardiac surgery and may cause permanent disabilities with severe consequences for quality of life. The objectives of this study were, first, to estimate the frequency of POCD after on-pump cardiac surgery in patients randomized to remifentanil- or sufentanil-based anesthesia and, second, to evaluate the association between POCD and quality of recovery and perioperative hemodynamics, respectively. DESIGN: Randomized study. SETTING: Postoperative cardiac recovery unit, University Hospital. PATIENTS: Sixty patients with ischemic heart disease scheduled for elective coronary artery bypass grafting +/- aortic valve replacement. INTERVENTIONS AND HANDLING: Randomized to either remifentanil or sufentanil anesthesia as basis opioid. Postoperative pain management consisted of morphine in both groups. MEASUREMENTS: Cognitive functioning evaluated preoperatively and on the 1st, 4th, and 30th postoperative day using the cognitive test from the Palo Alto Veterans Affairs Hospital. Perioperative invasive hemodynamics and the quality of recovery was evaluated by means of invasive measurements and an intensive care unit discharge score. MAIN RESULTS: No difference between opioids in POCD at any time. A negative correlation was found between preoperative cognitive function and POCD on the first postoperative day (r=-0.47; P=.0002). The fraction of patients with POCD on the first postoperative day was statistically greater in patients with more than 15minutes of Svo2 <60 (P=.037; chi(2) test). Among patients with postoperative ventilation time exceeding 300minutes, more patients had POCD on postoperative day 4 (P=.002). CONCLUSIONS: We could not demonstrate differences in POCD between remifentanil and sufentanil based anaesthesia, but in general, the fraction of patients with POCD seemed smaller than previously reported. We found an association between POCD and both perioperative low Svo2 and postoperative ventilation time, underlining the importance of perioperative stable hemodynamics and possible fast-track protocols with short ventilation times to attenuate POCD. PMID- 27555147 TI - Preoperative use of anxiolytic-sedative agents; are we on the right track? AB - STUDY OBJECTIVE: Although anxiolytic-sedative agents are used preoperatively since the advent of anesthesia, many aspects of this treatment, including the intended effects among which anxiolysis, effectiveness, and optimal agents, remain unclear. The objective of this study was to provide insight into the preoperative use of anxiolytic-sedative agents in the Netherlands and to relate the administration of these agents to the anxiolytic-sedative state of patients. DESIGN: Questionnaire study. SETTING: University, general, and specialized hospitals in the Netherlands. PATIENTS: One anesthesiologist in each hospital was asked for details about premedication in all elective procedures, except cardiothoracic surgery, in normal weighted adults in good to fair clinical condition. INTERVENTIONS: None. MEASUREMENTS: Estimated percentage of patients receiving anxiolytic-sedative premedication, type, dose, route of administration and timing of these agents, and anxiolytic state of patients when arriving at the holding area. MAIN RESULTS: All 8 university hospitals, 69 of 82 general hospitals and 2 of 3 specialized hospitals participated in this study (response rate, 84.9%). The estimated percentage of patients that received anxiolytic sedative agents was 46.8% for in-patients and 30.4% for day care patients (P<.0001), with large between-hospital variation. Midazolam (62.7%), oxazepam (20.2%), and temazepam (7.8%) were most frequently used and were virtually always orally administered 1 hour preoperatively. There was no relationship between use of anxiolytic-sedative agents and reduction of perceived anxiety (r=-0.09, P=.46 and r=-0.01, P=.91 for clinical and day care patients, respectively). CONCLUSIONS: Anxiolytic-sedative agents are used preoperatively in a substantial number of patients in the Netherlands, and the pharmacokinetic characteristics of many agents are not optimal of their intended use. In addition, we found no relationship with reduced anxiety. This study stresses the need for clear guidelines on preoperative use of anxiolytic-sedative agents. PMID- 27555148 TI - Triple A to triple S: From diagnosis, to anesthetic management of Allgrove syndrome. AB - INTRODUCTION: Allgrove syndrome (AS) is a rare autosomal recessive disorder characterized by achalasia cardia, alacrimia, and adrenocorticotropic hormone resistant adrenal insufficiency which is sometimes associated with autonomic dysfunction. It has also been referred to as the triple A syndrome in view of the cardinal symptoms described above. First described by Allgrove et al in 1978, the disorder usually presents mostly during the first decade of life. These patients have the threat of adrenal crisis, shock, and hypoglycemia and are usually on steroid supplementation. CASE REPORT: The anesthesiologist's encounter with such patients, although rare, is mostly for repair of the achalasia cardia. We thus report a similar case of AS in a 2-year-old girl who was scheduled to undergo Heller myotomy along with the preoperative evaluation and intraoperative management of the same. CONCLUSION: Being aware of the pathophysiology of AS gives useful insight about the disease and successful perioperative management in the form of the triple S strategy, that is, stress dose of steroids, slow induction and positioning, and finally maintenance of stable hemodynamics and euglycemia. PMID- 27555149 TI - A rare genetic variant of the ryanodine receptor in a suspected malignant hyperthermia susceptible patient. AB - Malignant hyperthermia (MH) remains a diagnostic challenge. This case report describes the anesthetic management of a suspected intraoperative MH episode and the subsequent, genetic sequence analysis of 3 genes associated with MH. The results of the molecular genetic testing revealed heterozygosity for a rare variant, c.12553G>A (p.Ala4185Thr), in the RYR1 gene encoding the ryanodine receptor. Although the RYR1 gene has previously been implicated in the pathogenesis of MH, (1) this particular variant has only been reported in one other case of MH; (2) the role for diagnostic genetic testing in the diagnosis of MH will be examined. PMID- 27555150 TI - Successful cases of S-ICD implantation performed under the serratus plane block. PMID- 27555151 TI - Prophylactic use of tranexamic acid combined with thrombelastogram guided coagulation management may reduce blood loss and allogeneic transfusion in pediatric hemispherectomy: case series. AB - Hemispherectomy is an established surgical procedure to treat medically refractory epilepsy caused by diffuse hemispheric diseases. The most common complication of hemispherectomy is intraoperative bleeding. Perioperative allogeneic blood transfusion increases mortality and morbidity in pediatric patients. Etiologies of massive blood loss during hemispherectomy include intraoperative diffuse vascular damage, antileptic drugs induced coagulation dysfunction, hyperfibrinolysis and dilutional coagulopathy. Great efforts should be made to minimize the need of blood transfusion. We present a series of three cases undergoing pediatric hemispherectomy, where a new algorithm was employed to manage coagulation. This new algorithm was mainly based on timely thrombelastogram analyses guided clotting factors supplement and continuous administration of tranexamic acid. In our cases, the amount of blood loss and subsequent allogeneic blood transfusion seemed to be less than literature reported. PMID- 27555152 TI - Cardiac arrest during radical nephrectomy due to a mass in the right ventricular outflow tract. AB - We report cardiac arrest due to obstruction of the right ventricular outflow tract (RVOT) caused by an RVOT mass that was not identified preoperatively. A 62 year-old woman with renal cell carcinoma (RCC) experienced deteriorating hypotension and bradycardia during radical nephrectomy. Hemodynamic stability was maintained on extracorporeal membrane oxygenation, and after surgery, she was transferred to the intensive care unit. On postoperative day 3, transthoracic echocardiography showed an intracardiac mass obstructing the RVOT, which caused severe functional pulmonary stenosis and moderate resting pulmonary hypertension. Despite maintaining extracorporeal membrane oxygenation, the patient died of cardiac arrest. Our findings suggest that it may be necessary to perform additional tests if RCC has invaded the renal vein and inferior vena cava or if a patient with RCC has abnormal cardiovascular symptoms without definite etiology for exclusion of cardiac metastasis or tumor thrombus. In addition, intraoperative transesophageal echocardiography might be the procedure of choice for the evaluation of these conditions because other diagnostic tests are difficult to perform during surgery. In conclusion, for patients with acute hemodynamic instability for whom other possible causes have been excluded, we recommend that anesthesiologists use transesophageal echocardiography to detect outflow tract obstruction or pulmonary thromboembolism and perform anesthetic management. PMID- 27555153 TI - A novel method to control the distal tip of nasotracheal tube. PMID- 27555154 TI - Can ondansetron be used in the treatment of subdural block? PMID- 27555155 TI - Branching of the radial artery in mid forearm: A rare anomaly. PMID- 27555156 TI - A rare cause of lower limb paralysis after epidural anesthesia. PMID- 27555157 TI - Regional cerebral oxygen saturation guided cerebral protection in a parturient with Takayasu's arteritis undergoing cesarean section: a case report. AB - The objective of this case report is to present the successful use of regional cerebral oxygen saturation (rScO2) monitoring guided cerebral protection for cesarean delivery in a parturient with Takayasu's arteritis at 38weeks' gestation. The parturient presented with impaired cerebral and renal perfusion. Titrated epidural anesthesia was performed. During the procedure, we used rScO2 guided cerebral protection strategies, which helped to optimize cerebral oxygen delivery and prevent cerebral complications. PMID- 27555158 TI - Evaluation of lifestyle changes before elective operation: a preliminary observational study. PMID- 27555159 TI - Hypoxia during general anesthesia? Unknown foreign body aspiration. AB - An 18-month-old male patient, classified as American Society of Anesthesiologists I, with bilateral inguinal hernia was scheduled for operation. Preanesthetic evaluation revealed history of completed medical treatment of acute bronchitis 10 days ago, and his respiratory examination was recorded as normal. He was successfully operated under general anesthesia with a laryngeal mask. After removal of the laryngeal mask, he displayed signs of hypoxia. Respiratory sounds were undetectable in the left thorax. He was intubated due to failure of adequate ventilation. Positive pressure ventilation and bronchodilators were administered to provide sufficient ventilation. In his chest X-ray, total atelectasis was determined in the left lung. Pleural effusion was ruled out with thoracic ultrasonography. Diagnostic rigid bronchoscopy was performed, and in left bronchial tree, hazelnut fragments were removed. The patient's hemodynamic and respiratory parameters recovered quickly after foreign body removal, and the patient was transferred to intensive care unit. His parents were questioned for persistent respiratory symptoms and they gave information about repeating respiratory tract infections in the last 3 months. We predict that displaced foreign body in lobar bronchus due to mechanical ventilation can cause this condition. PMID- 27555160 TI - A retrospective study showing the extent of compliance with perioperative guidelines in patients with coronary stents with regard to double antiplatelet therapy. AB - STUDY OBJECTIVE: To evaluate perioperative dual antiplatelet therapy management in patients with previously placed coronary stents. DESIGN: Retrospective medical record review. SETTING: Academic medical center. PATIENTS: A total of 1891 surgical cases performed at Vanderbilt University Medical Center in 2012 were evaluated using a perioperative database. Of these, 161 had complete data records that were evaluated using 2 evidence-based and expert opinion-supported protocols. INTERVENTIONS: N/A. MEASUREMENTS: This study is meant to evaluate perioperative antiplatelet management decisions in patients with coronary stents. MAIN RESULTS: Management decisions were consistent with guidelines regarding antiplatelet therapy in 13% (21/161) of patients. Of the 87% (140/161) of cases where decisions were not consistent, 88% (123/140) were due to discontinuing aspirin preoperatively when there was not a high risk of surgical bleeding. CONCLUSIONS: This study revealed suboptimal adherence to current perioperative antiplatelet management guidelines in patients with coronary stents. The lack of adherence to current guidelines is concerning and could be used to support the notion of an anesthesiologist-led Perioperative Surgical Home. PMID- 27555161 TI - Severe hypernatremia associated catheter malposition in an intensive care patient. AB - We present a catheter related severe hypernatremia in a 2-month-old baby who was admitted to the pediatric intensive care. Imbalance of plasma sodium is commonly seen in pediatric intensive care patients. The water and sodium balance is a complex process. Especially, brain and kidneys are the most important organs that affect the water and sodium balance. Other mechanisms of the cellular structure include osmoreceptors, Na-K ATPase systems, and vasopressin. Hypernatremia is usually an iatrogenic condition in hospitalized patients due to mismanagement of water electrolyte imbalance. Central venous catheterization is frequently used in pediatric intensive care patients. Complications of central venous catheter placement still continue despite the usage of ultrasound guidance. Malposition of central venous catheter in the brain veins should be kept in mind as a rare cause of iatrogenic hypernatremia. PMID- 27555162 TI - Where is an appropriate injection point for an ultrasound-guided transversus thoracic muscle plane block? PMID- 27555163 TI - Pulsed radiofrequency applied to the dorsal root ganglia for treatment of post stroke complex regional pain syndrome: A case series. AB - STUDY OBJECTIVE: Complex regional pain syndrome is a painful and disabling syndrome where the patient presents with neuropathic pain, edema, or vasomotor or pseudomotor abnormalities that are often refractory to treatment. Complex regional pain syndrome type 1 may occurs in stroke patients. Radiofrequency is a therapeutic modality that has been used for years for diseases associated with neuropathic pain. DESIGN: Case series report. SETTING: Selcuk University Hospital. PATIENTS: A 69-year-old woman and a 48-year-old women who suffered post stroke complex regional pain syndrome type 1. INTERVENTIONS: Pulsed radiofrequency current application to the cervical dorsal root ganglia. MEASUREMENTS: Pain reduction. MAIN RESULTS: The patients had complete resolution of their symptoms, which was maintained at 10 and 5 months of follow-up. CONCLUSIONS: These cases illustrates that pulsed radiofrequency applied to cervical dorsal root ganglia might play a significant role in multi-modal approach of complex regional pain syndrome type 1 management after stroke. Further randomized, controlled studies are needed to support this argument. PMID- 27555164 TI - Locating the optimal internal jugular target site for central venous line placement. AB - STUDY OBJECTIVE: Historically, the placement of internal jugular central venous lines has been accomplished by using external landmarks to help identify target rich locations in order to steer clear of dangerous structures. This paradigm is largely being displaced, as ultrasound has become routine practice, raising new considerations regarding target locations and risk mitigation. Most human anatomy texts depict the internal jugular vein as a straight columnar structure that exits the cranial vault the same size that it enters the thoracic cavity. We dispute the notion that the internal jugulars are cylindrical columns that symmetrically descend into the thoracic cavity, and purport that they are asymmetric conical structures. DESIGN: The primary aim of this study was to evaluate 100 consecutive adult chest and neck computed tomography exams that were imaged at an inpatient hospital. We measured the internal jugular on the left and right sides at three different levels to look for differences in size as the internal jugular descends into the thoracic cavity. MAIN RESULTS: We revealed that as the internal jugular descends into the thorax, the area of the vessel increases and geometrically resembles a conical structure. We also reconfirmed that the left internal jugular is smaller than the right internal jugular. CONCLUSIONS: Understanding that the largest target area for central venous line placement is the lower portion of the right internal jugular vein will help to better target vascular access for central line placement. This is the first study the authors are aware of that depicts the internal jugular as a conical structure as opposed to the commonly depicted symmetrical columnar structure frequently illustrated in anatomy textbooks. This target area does come with additional risk, as the closer you get to the thoracic cavity, the greater the chances for lung injury. PMID- 27555165 TI - Time-dependent changes in epidural catheter aspirate after injection of a local anesthetic. AB - STUDY OBJECTIVE: A glucose check is used for investigation of a suspected accidental dural puncture in epidural anesthesia. However, glucose-positive clear fluid is sometimes aspirated from an epidural catheter in cases without clinical evidence of puncture. The goal of the study was to investigate time-dependent changes in the aspirate composition after injection of a local anesthetic into the epidural space. DESIGN: Observational study. SETTING: Operating rooms at Hamamatsu University Hospital. PATIENTS: The subjects were 30 patients (ASA I or II) undergoing surgery with combined epidural and general anesthesia. INTERVENTIONS: After epidural injection of local anesthetics, aspiration through the catheter was performed every 10min until fluid could not be aspirated. pH, Na, K, Cl, Ca and glucose were measured in fluid samples using a blood gas analysis apparatus. MAIN RESULTS: No patients had pain or clinical signs suggesting dural puncture throughout the perioperative period. Fluid aspiration was possible in 15 patients (50%) after 10min and in 7, 3, 2 and 2 patients after 20, 30, 40 and 50min, respectively. Glucose was detected in each aspirated fluid sample and gradually increased with time to become closer to the level in cerebrospinal fluid (CSF). Each electrolyte also changed to approach the level found in CSF. CONCLUSIONS: A glucose check may increase the risk of a false positive finding for accidental dural puncture with increasing time after local anesthetic injection. Conversely, detection of glucose at the time of epidural catheter placement may provide useful information for detection of accidental dural puncture. PMID- 27555166 TI - Does intravenous induction dosing among patients undergoing gastrointestinal surgical procedures follow current recommendations: a study of contemporary practice. AB - STUDY OBJECTIVE: It is recommended to correct intravenous induction doses by up to 50% for patients older than 65 years. The objectives were to determine (a) the degree to which anesthesia providers correct induction doses for age and (b) additionally adjust for American Society of Anesthesiologists physical status (ASA-PS) class (severity of illness) and (c) whether postinduction hypotension is more common among patients aged >65. DESIGN: Retrospective chart review. SETTING: Academic medical center. PATIENTS: A total of 1869 adult patients receiving general anesthesia for GI surgical procedures from February 2013 to January 2014. MEASUREMENTS: Patients were divided into 3 age groups (age <65, 65-79, >=80 years) and then further stratified into ASA-PS class (I/II vs III/IV). Multiple pairwise comparisons were conducted using Welch t tests for continuous variables to determine whether dosing was different for the older groups vs the younger group; separate analyses were performed within and across ASA-PS class. This approach was also used to determine differences in mean arterial pressure change in the older groups vs the younger group, whereas the rates of hypotension among different age groups were compared by Cochran-Armitage trend test. MAIN RESULTS: No significant decrease in dosing between age groups was observed for fentanyl and midazolam. For propofol, there was a significantly lower dosing for older patients: 17% for patients aged 65-79 and 29% for those aged >80, which was still in less than the recommendations. An inverse relationship was observed between propofol dosing and ASA-PS class, but no consistent relationship was noted for fentanyl and midazolam. There were a significantly larger drop in mean arterial pressure and a greater likelihood of hypotension following induction in patients aged 65-79 years and >80 years as compared with those aged <65 years. CONCLUSIONS: This study shows that the administered dose of anesthetic induction agents is significantly higher than that recommended for patients older than 65 years. This failure to age-adjust dose may contribute to hypotensive episodes. PMID- 27555167 TI - Transversus abdominis plane block for analgesia in spinal muscular atrophy patient. PMID- 27555168 TI - Muscle relaxant facilitates i-gel insertion by novice doctors: A prospective randomized controlled trial. AB - STUDY OBJECTIVE: This study aimed to determine whether muscle relaxants facilitates insertion efficacy of the i-gel supraglottic device (i-gel) by novice doctors in anesthetized patients. DESIGN: Randomized clinical trial. SETTING: Operating room. PATIENTS: Seventy adult patients scheduled for elective surgery under general anesthesia. INTERVENTIONS: Seventy adult patients were assigned to the rocuronium (MR group; 35 patients) or control group (C group; 35 patients). Anesthesia was induced with propofol and remifentanil, and 0.9mgkg(-1) rocuronium was administered in the MR group. MEASUREMENTS: The number of attempts to successful insertion, sealing pressure, and subjective difficulty of insertion were compared between the groups. MAIN RESULTS: The total number of insertion attempts were as follows: one (MR group, 17 cases; C group, 4 cases), two (MR group, 13 cases; C group, 14 cases), three (MR group, 4 cases; C group, 14 cases), and failure (MR group, 1 case; C group, 3 cases), which was significantly different (P<.001). Sealing pressure was significantly higher in the MR group than in the C group (MR group, 22.1+/-5.4 cmH2O; C group, 18.7+/-3.2 cmH2O, P<.001). Subjective difficulty of insertion was significantly lower in the MR group than in the C group (C group, 72.4+/-19.0mm; MR group, 29.4+/-18.3mm; P<.001). CONCLUSIONS: Our randomized clinical trial suggests that muscle relaxation facilitates i-gel insertion efficacy in anesthetized patients, as assessed by successful insertion rate, sealing pressure, and subjective difficulty of insertion. PMID- 27555169 TI - Difficult airway management using Pentax-AWS Airwayscope with pediatric Intlock and tracheal tube introducer in Goldenhar syndrome patient. PMID- 27555170 TI - Therapeutic hypothermia after cardiac arrest is not associated with favorable neurological outcome: a meta-analysis. AB - BACKGROUND: Cardiac arrest is associated with very high mortality and causes neurological dysfunction in the survivors. Therapeutic hypothermia is one of the recommended modality in the postarrest management. However, recent findings question its benefit in postarrest management. This meta-analysis has been conceptualized to quantify clinical benefit of therapeutic hypothermia in post cardiac arrest patients. METHODS: Prospective, randomized, and quasi-randomized controlled trials comparing the efficacy of therapeutic hypothermia in post cardiac arrest adult population with a post-cardiac arrest management protocol that does not include therapeutic hypothermia were included in this meta analysis. Two authors independently searched PubMed, PubMed Central, Scopus, and Central Register of Clinical Trials of the Cochrane Collaboration for potentially eligible trials. RESULTS: Data of 1399 patients from 6 controlled trials have been included in this systematic review and meta-analysis. Therapeutic hypothermia does not provide any benefit in favorable neurological outcome (P=.06; odds ratio, 1.80; 95% confidence interval [CI], 0.97-3.35; n=1384), in survival at hospital discharge (P=.58; odds ratio, 1.16; 95% CI, 0.69-1.96; n=1399), and in long-term survival (P=.36; odds ratio, 1.32; 95% CI, 0.73-2.39; n=1292). Therapeutic hypothermia also increases incidence of pneumonia (P=.02; odds ratio, 1.30; 95% CI, 1.04-1.64; n=1204; number needed to harm, 15). CONCLUSION: Therapeutic hypothermia in the post-cardiac arrest management protocol does not provide any benefit in favorable neurological outcome, survival to hospital discharge, and long term survival. Incidence of pneumonia may be increased with the use of therapeutic hypothermia. PMID- 27555171 TI - Elective use of the Ventrain for upper airway obstruction during high-frequency jet ventilation. AB - The safety of high pressure source ventilation (jet ventilation) is dependent upon upper airway patency to facilitate adequate passive expiration and prevent increasing intrathoracic pressure and its associated deleterious sequelae. Distortions in airway anatomy may make passive expiration inadequate or impossible in some patients. We report the elective use of the Ventrain device to provide ventilation in a clinical setting of upper airway obstruction in a patient with post radiation fibrosis that had previously prevented passive expiration during attempted high pressure source ventilation. PMID- 27555172 TI - Impact of spinal versus general anesthesia on postoperative pain and long term recurrence after surgery for pilonidal disease. AB - STUDY OBJECTIVE: To assess the effect of the kind of anesthesia on postoperative pain and long term recurrence rate in pilonidal sinus disease. DESIGN: Retrospective study. SETTING: Surgical departments of German Armed Forces Hospitals in Hamburg, Bad Zwischenahn and Hamm. PATIENTS: 583 pilonidal sinus disease (PSD) surgery patients operated for pilonidal disease. INTERVENTION: Interview of randomly selected patients, who had been followed up to 20years after PSD surgery. MEASUREMENTS: Analysis of long term recurrence-free survival and postoperative pain scores among patients who received different anesthesia modalities. MAIN RESULTS: Recurrence occurred in 21.97% of patients who received general anesthesia with intubation (ITN), in 23.32% of spinal anesthesia (SPA), and in 31.91% of local- or cryoanesthesia. Our data indicate that there was no significant difference in recurrence-free time between the types of anesthesia in any of the surgical procedures applied. Pain scores of patients who underwent primary midline closure (4.74+/-2.63, 95% CI [4.36, 5.12]) were significantly lower than pain scores of patients who underwent marsupialization (6.12+/-2.71, 95% CI [5.17, 7.07]) or primary open treatment (6.09+/-2.79, 95% CI [5.79, 6.39]) (P<.0001). Post-operative pain scores did not differ between patients who received ITN or SPA. Cryo- or local anesthesia resulted in significantly lower post-operative pain scores compared to ITN (P=.0089) or SPA (P=.0031). CONCLUSION: The use of SPA or general anesthesia did not affect the long term recurrence rate in PSD. Postoperative pain experienced either in-hospital or after discharge did not differ between patients receiving ITN or SPA. With other cryo- or local anesthesia, postoperative pain score was significantly reduced in any surgical procedure. However, due to the higher recurrence rate after cryo- or local anesthesia, only SPA and general anesthesia should be applied. The decision whether spinal or general anesthesia is applied in PSD surgery remains a purely anesthesiological decision based on standard considerations. PMID- 27555173 TI - Both lavender fleur oil and unscented oil aromatherapy reduce preoperative anxiety in breast surgery patients: a randomized trial. AB - STUDY OBJECTIVE: The objective of this study was to determine whether lavender fleur oil (LFO) aromatherapy would reduce anxiety when administered to women before undergoing breast surgery. DESIGN: This was a single-site, randomized study comparing the effect of LFO to unscented oil (UO). SETTING: The study was conducted in the preoperative holding area of the ambulatory surgery department of NYU Langone Medical Center. PATIENTS: Ninety three women, 18 years and older, scheduled for breast surgery. Women meeting inclusion/exclusion criteria were randomized to either LFO or UO aromatherapy and were blind to their assigned treatment. OUTCOME MEASURES: Subjects completed a Speilberger State Anxiety Inventory for Adults (STAI) before and after aromatherapy. Vital signs were recorded before and after aromatherapy. RESULTS: STAI-State questions were divided into positive and negative emotions for analysis. Before aromatherapy, there was no significant difference between groups by individual questions or overall average answer of either positive or negative questions. The use of both LFO and UO increased the positive STAI score totals, with the LFO group having a slightly, but statistically significant, greater increase. Both resulted in a statistically significant decrease in the negative score totals after treatment. There were no differences in vital signs between groups for either treatment. Following the conclusion of the trial LFO was analyzed and found to contain a very low content of the 2 major Lavandula angustifolia constituents. CONCLUSIONS: Both LFO and UO aromatherapy treatments lowered anxiety before surgery despite no significant changes in vital signs. LFO treatment generated a slight but statistically significant increase in positive feelings compared with UO treatment. It is probable that the beneficial effect observed was due to both aromatherapy with LFO and a placebo effect related to the added attention given to the patients. PMID- 27555174 TI - Shoulder position influences the location of the musculocutaneous nerve in the axillary fossa. AB - In the axillary fossa, the musculocutaneous nerve (MC) is generally distant from the axillary artery and from the other brachial plexus nerves. In that way, MC requires a specific block. We observed that the location of MC is influenced by the position of the patient's arm and shoulder. Abduction of the shoulder significantly reduced the distance between the MC and the axillary artery. This change in the location of the MC is probably due to the moving of the nerve because of muscle rearrangements and the ability to achieve better proximity of the probe in the axillary fossae. PMID- 27555175 TI - A survey of residency program directors in anesthesiology regarding mentorship of residents. AB - INTRODUCTION: Mentorship of residents has been extensively studied within many academic specialties, but not anesthesia. The purpose of this study is to determine the prevalence of formal mentorship programs among anesthesia residency programs accredited by the Accreditation Council for Graduate Medical Education in the United States by surveying residency directors. The secondary goals of the study are to describe the programs that exist and identify areas that residency directors think should be the focus of mentoring. METHODS: Our survey was designed based on previous surveys administered to residency program directors from other specialties. After determination of exempt status by our institutional review board, the survey was administered via e-mail to program directors of Accreditation Council for Graduate Medical Education-accredited anesthesiology residencies. RESULTS: Response rate was 34% (45/131). The sample consisted of mainly university-based programs (93%). Most (88%) had a mentorship program in place. There was little consistency between methods of forming faculty-resident mentor pairs. Most mentors (84%) and mentees (79%) did not evaluate their programs. Nearly all program directors agree that mentorship is an important tool for resident development (90.6%) and that it is important to have a mentor during training (90.6%). Program directors identified the areas of career planning, professionalism, and achieving a balance between personal, career, and family demands to be the most valuable subjects to address in a mentoring relationship. CONCLUSION: Anesthesiology is currently underrepresented in the trainee mentoring literature. There is significant support for mentorship during resident training; however, the low rates of training for faculty and minimal evaluation by residents and faculty raise the question as to the efficacy of the existing programs. There is a need for more investigation of anesthesia residents' goals and perceptions of mentorship, and a more detailed evaluation of existing mentorship programs to determine the ideal structure of a mentoring program. PMID- 27555176 TI - Use of cuffed tracheal tubes in neonates, infants and children: A practice survey of members of the Society of Pediatric Anesthesia. AB - STUDY OBJECTIVE: This study aimed to characterize the current practice patterns with cuffed tracheal tubes (CTT) in neonates, infants, and children among members of the Society of Pediatric Anesthesia (SPA). DESIGN AND SETTING: An electronic mail survey was distributed using Survey Monkey to members of SPA between December 2013 and February 2014. Each member was permitted one response. PATIENTS/INTERVENTION/MEASUREMENTS: Not applicable as this is a practice survey study. MAIN RESULTS: A total of 805 (28%) of the 2901 members of the SPA responded. Of the respondents, 88% were from the US, 83% were fellowship trained, 82% practiced pediatric anesthesia >50% of the time, and 65% practiced in academic centers. Eighty-five percent used CTT >50% of the time in children >2 years and 60% used CTT in full-term neonates >50% of the time. Twenty-nine percent reported always using CTT whereas 5% reported never using CTT. Those in practice <5 years, who were fellowship trained or in academic practice used CTT more often in neonates compared with those in practice >20 years, not fellowship trained or in private practice (P< .0001, P= .0003 and P= .0005, respectively). The most common reason for avoiding CTT was concern about post-extubation stridor (39%). Almost 70% of respondents accept the TT if it passes the subglottis without resistance and has a leak at 15 to 20 cmH2O. More than 60% of respondents do not monitor cuff pressures in CTT. CONCLUSION: A majority of SPA members routinely use CTT in neonates, infants and children. PMID- 27555177 TI - Redesigning an airway cart using lean methodology. AB - STUDY OBJECTIVE: Use lean methodology to create a more efficient difficult airway management equipment transport and setup. DESIGN: The 5S steps of sort, set in order, sweep, standardize, and sustain were used to create a redesigned airway cart. The 5S steps provided the framework to separate the needed from unneeded equipment, logical equipment placement on the cart, and a plan to maintain improvements. Simulations were utilized to compare the revised airway cart to the previous airway equipment storage. SETTING: Hospital operating rooms and equipment storage rooms. PATIENTS: Simulated difficult airway scenarios without patient involvement. INTERVENTION: Difficult airway equipment 5S process. MEASUREMENTS: Total pieces and cost of airway equipment before and after intervention. Walking distance and time to retrieve equipment, setup equipment, and setup defect rate during a simulation. MAIN RESULTS: Previously, airway equipment was stored in 4 locations which was reduced a single difficult airway cart. The total pieces of equipment stored was reduced 89% and the cost of disposable equipment inventory was reduced 81%. Simulations looking at the acquisition and setup of equipment during a difficult airway scenario revealed a 39% reduction in equipment set up time, a 77% reduction in non-valued-added set up time, and a 74% reduction in walking distance. There was no difference in set up defect rates. CONCLUSION: Application of this lean method resulted in a revised single cart with equipment pared down to only what is needed, arranged according to frequency and order of use in a difficult airway. In a simulated difficult airway, there was a reduction in non-value-added time and walking distance to retrieve the equipment. PMID- 27555178 TI - Comparision of clonidine and dexmedetomidine for attenuation of laryngoscopy and intubation response - A randomized controlled trial. AB - BACKGROUND: Clonidine and dexmedetomidine are alpha-2 agonists with beneficial effect on the hemodynamic response to laryngoscopy and intubation. The present study was designed to evaluate and compare the efficacy of intravenous clonidine 1 MUg/kg, and dexmedetomidine in doses of 0.5 MUg/kg and 1 MUg/kg, for blunting the hemodynamic changes during laryngoscopy and intubation. METHOD: Adult patients of ASA physical grade I/II scheduled for surgery under general anaesthesia with endotracheal tube were randomly divided into three groups using a computer generated random number table, each group receiving one of the following drugs prior to induction of anaesthesia, by a blinded anaesthesiologist in a volume of 100 mL infused intravenously over 20 minutes: clonidine 1 MUg/kg, or dexmedetomidine 0.5 MUg/kg, or dexmedetomidine 1 MUg/kg. General anaesthesia was induced using standard technique and intubations performed by same anaesthesiologist. Heart rate and mean blood pressure were recorded in pre operative room (baseline) and again at 1 minute, 3 minutes, 5 minutes and 10 minutes after intubation. An increase in heart rate and/or mean blood pressure by >20% above baseline values during observation period was taken to indicate a positive intubation response. RESULTS: The incidence of intubation response was similar in all three groups (P>.05). The number of patients developing hypotension was significantly higher in group receiving dexmedetomidine1MUg/kg group (P<.005) as compared to other two groups. Both the groups receiving dexmedetomidine had higher number of patients developing bradycardia as compared to patients receiving clonidine. DISCUSSION & CONCLUSION: Dexmedetomidine 0.5 MUg/kg, 1 MUg/kg and clonidine 1 MUg/kg attenuate the laryngoscopy and intubation response but Clonidine 1 MUg/kg was associated with lesser side effects. PMID- 27555179 TI - Efficacy of premedication with intranasal dexmedetomidine on inhalational induction and postoperative emergence agitation in pediatric undergoing cataract surgery with sevoflurane. AB - STUDY OBJECTIVES: This study aimed to test the hypothesis that premedication with a single dose of intranasal dexmedetomidine (DEX) could not only reduce preoperative anxiety but also minimize the emergence agitation in children undergoing cataract surgery with sevoflurane anesthesia. DESIGN: Single-blinded, randomized, placebo-controlled clinical comparison study. SETTING: Academic medical center. PATIENTS: Ninety American Society of Anesthesiologists physical status 1 and 2 children scheduled for cataract surgery. INTERVENTIONS: Patients were randomized into 3 groups: group D1, group D2, and saline group (group C), in which the children received 1 or 2 MUg/kg of intranasal DEX or saline, respectively, and each group comprises 30 patients. MEASUREMENTS: The mask induction score and the incidences of postoperative emergence agitation evaluated by the Pediatric Anesthesia Emergence Delirium scale were assessed. The emergence time, postanesthesia care unit (PACU) stay time, and any adverse events were recorded. MAIN RESULTS: The mask induction scores were significantly higher in the saline group than those in the D1 and D2 groups (P<.001). The incidences of emergence agitation in the D1 and D2 groups were significantly lower than that in the saline group (7/30 in group D1 and 3/30 in group D2 vs 24/30 in group C, P<.001). The emergence time and PACU stay time were comparable among the 3 groups (P>.05). The emergence time and PACU stay time did not differ significantly in DEX-treated groups as compared with the saline group; there were no differences between 1- and 2-MUg/kg groups. None of the patients exhibited significant clinical complications. CONCLUSION: Intranasal DEX (1 or 2 MUg/kg) dose independently improves the incidences of mask acceptance and prevents the incidences of postoperative emergency agitation mainly from sevoflurane without delaying the emergency time or inducing severe adverse events. PMID- 27555180 TI - Tube in a tube: a ventilating conduit for intubating laryngeal mask airway-guided intubation. PMID- 27555181 TI - Laryngeal mask airway ProSeal provides higher oropharyngeal leak pressure than i gel in adult patients under general anesthesia: a meta-analysis. AB - STUDY OBJECTIVE: i-gel is a single-use supraglottic airway device that has a gastric drain tube similar to laryngeal mask airway (LMA) ProSeal. Randomized trials, when compared i-gel with LMA ProSeal, reported a differing results. Primary objective of this study is to compare LMA ProSeal and i-gel in terms of oropharyngeal leak pressure. DESIGN: Meta-analysis of randomized controlled trials where i-gel has been compared to LMA ProSeal in adult airway management during general anesthesia. SETTING: Teaching institutions. MEASUREMENTS: PubMed, PubMed Central, and Cochrane databases were searched with search words "i-gel," "i-gel laryngeal mask airway," "i-gel ProSeal," and "i-gel LMA ProSeal" to find out the randomized controlled trials that compared i-gel with LMA ProSeal in terms of safety and efficacy. A total of 10 prospective randomized trials have been included in this meta-analysis. MAIN RESULTS: LMA ProSeal provides higher oropharyngeal leak pressure than i-gel (mean difference, 3.37 cm H2O; 95% confidence interval, 1.80-4.95 cm H2O; P< .0001). Time to insert the device, first insertion success rate, and ease of gastric tube insertion are similar with both the devices, but i-gel may be easier to insert. Although the reported complications are not frequent and not very serious, a significantly higher blood staining on the mask has been noted with LMA ProSeal (odds ratio, 0.27; 95% confidence interval, 0.13-0.56; P= .0004). CONCLUSION: LMA ProSeal may still remain the supraglottic device of choice over i-gel in adult patients during general anesthesia as it provided better seal against leak pressure with comparable device insertion characteristics. PMID- 27555182 TI - Green urine: A bezoar effect. AB - The green color in urine may suggest the presence of a severe pathology needing treatment. Many different potential causes of green urine have previously been reported. In our case, after ruling out other potential causes of green urine, it was suggested that the surgical manipulation of the paralytic ileum might have induced the reabsorption of the methylene blue which had been retained in the bowel (bezoar effect), even 96 hours after the nasogastric administration. CONCLUSIONS: The staff should keep in mind this possible effect due to methylene blue to recognize early and avoid unnecessary laboratory tests. AUTHORS SUMMARY: This case report illustrates the significance of urine discoloration, sometimes indicate the presence of a systemic disorder and some rare cases, this phenomenon has no pathologic effects. To our knowledge, this is the first case report of a green urine by drug bezoar due methylene blue in children. PMID- 27555183 TI - A comparison of classic laryngeal mask airway insertion between lightwand- and standard index finger-guided techniques. AB - STUDY OBJECTIVE: To compare the efficacy of lightwand-guided classic laryngeal mask airway (cLMA) real-time insertion technique with the standard recommended index finger-guided insertion technique. DESIGN: Prospective, randomized controlled study. SETTING: University-affiliated hospital. PATIENTS: Three hundred patients undergoing minor gynecological or orthopedic surgeries under general anesthesia using the cLMA as an airway management tool. INTERVENTIONS: Patients were randomly divided into either lightwand-guided group or standard group. MEASUREMENTS: Fiberoptic bronchoscopy was used to determine the cLMA position after a cLMA was inserted. The first attempt and total success rates of the cLMA insertion, insertion time, distances from the end of cLMA pilot tube to the upper central incisors, views of fiberoptic bronchoscopy, blood staining, tidal volume, airway pressure, end-tidal CO2, SpO2, noninvasive hemodynamic parameters, and others were compared. MAIN RESULTS: The cLMA was all successfully inserted within 3 attempts except for 2 patients in the standard group. The success rates of lightwand-guided insertion technique at first attempt were significantly higher than standard insertion technique; the ideal view rates assessed by fiberoptic bronchoscopy in lightwand-guided group patients were also significantly higher than in standard group patients, but the insertion time of first successful attempt was similar; the blood staining rates on the cLMA in lightwand-guided group patients were significantly less than in standard group patients. The depths of cLMA insertion in standard group patients were significantly deeper than those in lightwand-guided group patients. There was no significant difference in end-tidal CO2, SpO2, airway pressure, and hemodynamic variables. CONCLUSION: Lightwand-guided cLMA insertion technique can provide a more objective indicator for correct cLMA positioning, higher first attempt success rates, better glottic views, and less damage to oropharyngeal or esophagus tissues than standard index finger-guided cLMA insertion technique. PMID- 27555184 TI - Reversal of profound neuromuscular blockade with sugammadex in an infant after bronchial foreign body removal. AB - Sugammadex is a selective chemical agent that can reverse neuromuscular blockade induced by vecuronium and rocuronium. The aim of this report is to discuss the effectiveness of sugammadex in the reversal of neuromuscular blockade in children younger than 2 years. A 16-month-old boy, weighing 10 kg, was admitted to the pediatric emergency department due to choking, cyanosis, and severe respiratory distress that occurred while he was eating peanuts. In the emergency department, the patient's condition deteriorated, and he went into respiratory arrest. He was immediately intubated and taken to the operating room. A rigid bronchoscopy was performed under general anesthesia, with administration of intravenous pentothal (5 mg/kg), rocuronium (0.6 mg/kg), and fentanyl (0.5 MUg/kg) in the operating room. The foreign body was removed within 6 minutes, and the profound neuromuscular blockade was reversed with a dose of 2 mg/kg sugammadex. He was extubated successfully after obtaining the spontaneous respiratory activity, and adequate breathing was restored. Clinical use of sugammadex in children younger than 2 years is not recommended because of the lack of clinical studies. In this case report, the profound neuromuscular blockade was successfully reversed with a dose of 2 mg/kg sugammadex in a 16-month-old boy. However, more prospective clinical studies are required for the safe use of this agent in children. PMID- 27555185 TI - Reliable low-molecular-weight heparin reversal in a child undergoing emergency surgery: a case report. AB - Low-molecular-weight heparin neutralization using protamine alone can be unreliable, especially in cases of immediate reversal for emergency surgery. Here, we describe a unique case of a 17-month-old girl with a history of glioneuronal tumor and corresponding hydrocephalus status post debulking and ventriculoperitoneal shunt placement, who was placed on enoxaparin after the development of a sagittal sinus thrombosis. Patient presented for emergency craniectomy and evacuation of subdural bleed after a fall while on therapeutic dose of enoxaparin. Protamine and fresh frozen plasma were used in the patient's perioperative course providing a reliable reversal of enoxaparin. PMID- 27555186 TI - Unexpected falsely low pulse oximeter measurements in a child with hemoglobin Southampton. PMID- 27555187 TI - Comparison of caudal epidural block and ultrasonography-guided transversus abdominis plane block for pain relief in children undergoing lower abdominal surgery. AB - STUDY OBJECTIVE: We conducted this study to compare the efficacy of caudal epidural block (CEB) vs ultrasonography-guided transversus abdominis plane (TAP) block for providing postoperative pain relief in children scheduled for lower abdominal surgery. Whereas the primary objective was to compare the duration of postoperative analgesia, the secondary objectives included comparative assessment (TAP vs CEB) of quality of pain relief in the first 24hours postoperatively and rescue analgesia requirements. DESIGN: Randomized-control, prospective, observer blinded, 2-arm, single-center comparison. SETTING: Operating room, postoperative recovery area. PATIENTS: Eighty-children, aged 2-6years, of American Society of Anesthesiologists physical status I/II scheduled to undergo unilateral lower abdominal surgery under general anesthesia. INTERVENTIONS: The recruited children were randomly allocated to receive under general anesthesia either CEB (group C, 0.75 mL/kg of 0.25% bupivacaine) or ultrasonography-guided administration of TAP block (group T, 0.5 mL/kg of 0.25% bupivacaine). MEASUREMENTS: Intraoperative: heart rate and noninvasive blood pressure; postoperative: pain profile, including duration of postoperative analgesia, quality of pain relief, and rescue analgesia requirements. MAIN RESULTS: The median duration of postoperative analgesia was significantly greater in children who received CEB than those who were administered TAP block (group C: 362.5 minutes [172.5-693.75] vs group T: 210 minutes [108.75-362.5]; P<.05). No difference was found in the incidence of postoperative pain up to 6 hours from the point of initiation of assessment (group C: 47.2% vs group T: 55.9%; P>.05). The children who received CEB experienced greater incidence of pain in the 6- to 24-hour postoperative interval than those administered TAP block (group C: 75% vs group T: 44.1%; P<.05). Although there was no difference in the rescue analgesia requirements, the number of children not requiring any rescue analgesia in the first 24 hours postoperatively was significantly higher in the TAP group (group C: n=2 vs group T: n=8; P<.05). CONCLUSIONS: In children undergoing lower abdominal surgery, CEB provides a significantly prolonged duration of postoperative analgesia when compared with ultrasonography-guided TAP block. PMID- 27555188 TI - A comparison between the GlideScope(r) classic and GlideScope(r) direct video laryngoscopes and direct laryngoscopy for nasotracheal intubation. AB - DESIGN: Prospective, randomized, clinical trial. SETTING: University hospital operation room. PATIENTS: 104 patients scheduled for elective dental or maxillofacial surgery were randomized to two groups: GlideScope(r) classic (GSc) and GlideScope(r) direct (GSd). INTERVENTIONS: We compared the video laryngoscopes GSc and GSd with each other and with direct laryngoscopy (DL) for nasotracheal intubation with regard to visualization of the glottis, intubation success rate, and required time for and ease of intubation. The aim of the study was to determine whether the use of the video monitor alone reduced the difficulty of nasotracheal intubation, and also to investigate whether the GSc, with its blade designed for difficult airways, had an additional advantage over the video-assisted Macintosh blade (GSd). In both groups the investigators first performed laryngoscopy using the GSd blade, first with the monitor concealed and then with it visible. In the GSd group the tube was then inserted into the trachea with the video monitor screen visible. In the GSc group, the GSd blade was exchanged for the GSc blade, which was then used when inserting the tube with the screen visible. RESULTS: The success rates and the times required for the video-assisted nasotracheal intubation did not differ significantly between the groups. A better view was obtained more often in the GSc group. In both groups there was a significant difference between direct laryngoscopy and the video assisted intubation technique. Overall, using the video monitor improved the C-L scores by one grade in 52% and by two grades in 11% of the patients. CONCLUSIONS: Video laryngoscopes increase the ease of nasotracheal intubation. The GSc blade might provide a better view of the laryngeal structures in case of a difficult airway than the GSd blade. Video laryngoscopy per se gives a better view of the glottis than direct laryngoscopy. PMID- 27555189 TI - An atypical presentation of chronic Stanford type A aortic dissection during pregnancy. AB - Aortic dissection is a rare but devastating disease during pregnancy, usually presenting with sharp pains on the chest or back. We report a pregnant woman suffering from chronic Stanford type A aortic dissection presented with atypical symptoms without pain in the third trimester with markedly dilated aortic root and congestive heart failure, who received concomitant cesarean delivery and aortic repair with good maternal and fetal outcomes. Multidisciplinary approach and tight hemodynamic control are very important. More attention should be paid to those atypical symptoms so as to early identify this scarce but disastrous disease during pregnancy. PMID- 27555190 TI - Concurrent pericardial and pleural effusions: a double jeopardy. AB - A 19-year-old man with large malignant pleural and pericardial effusions with tamponade physiology and signs of congestive heart failure presented for emergent subxiphoid pericardial window. Surgical drainage of the pericardium was complicated by a paradoxical cardiovascular collapse that failed to respond to pressors and intravenous fluids. Suspecting a pericardial perforation, a median sternotomy was performed and revealed an intact heart. The arterial pressure was promptly restored after drainage of the pleural effusion. It is proposed that, in patients presenting with tamponading pericardial and pleural effusions, drainage of the pleural effusion be given priority. The pathophysiology of low cardiac output states resulting from pericardial and large pleural effusion is discussed and the literature reviewed. PMID- 27555191 TI - Effect of Subcutaneous Unfractionated Heparin Prophylaxis on Activated Partial Thromboplastin Time: A Retrospective Evaluation. AB - STUDY OBJECTIVE: Characterize the incidence of elevated aPTT results in patients treated with prophylactic, subcutaneous unfractionated heparin (UFH). DESIGN: Retrospective, cohort analysis. SETTING: Single-center, university hospital. MEASUREMENTS: Evaluation of 257 patients with activated partial thromboplastin time (aPTT) testing both prior to and following subcutaneous (SC) unfractionated heparin (UFH) therapy. MAIN RESULTS: Evaluated patients received UFH 5000 units every 8 hours. Baseline aPTT values were within the normal range (mean+/-SD, 32.0+/-8.5 seconds). After initiation of UFH, aPTT values increased (mean+/-SD, 37.6+/-15.2 seconds). After 24 hours of SC UFH, mean aPTT values (mean+/-SD, 38.6+/-15.5) exceeded the normal laboratory range (23.3-35.7 seconds). An elevated aPTT result after UFH was associated with baseline aPTT, length of therapy, and weight-based UFH dose. A significant association was not identified between aPTT elevation and age, race, sex, history of liver disease, type of admission, or transfusion of blood products. CONCLUSIONS: Treatment with UFH resulted in a small, but significant, increase in aPTT. PMID- 27555192 TI - American-trained Chinese anesthesiologists: how are they doing? AB - More than 60 years have passed since 3 pioneer Chinese anesthesiologists were trained by American physicians. After returning to China, they applied their new knowledge and skills to develop a new anesthesia specialty in their own country. Over the past 2 decades, close to 600 Chinese medical graduates have been trained in the United States and have become part of the American anesthesia workforce. Unlike their elder generation, they did not go back to China after their training. People are always wondering how this new generation of American-trained Chinese anesthesiologists is doing in a different culture and different health care and political systems. This review indicates that these newly American trained Chinese anesthesiologists not only provide high-quality patient care but also conduct outstanding anesthesia teaching and research. In addition, as their pioneer anesthesiologists did in China, they use professional organizations and publications as 2 major means to advance professional development and promote academic exchanges between Chinese and American anesthesiologists, through which American anesthesiology continues to have influence on modern Chinese anesthesiology. PMID- 27555193 TI - Transversus abdominis plane block for laparoscopic inguinal hernia repair: a randomized trial. AB - BACKGROUND: Pain after laparoscopic inguinal hernia surgery can be moderate to severe, interfering with return to normal activity. The study aimed to assess the efficacy of bilateral ultrasound-guided (USG) transversus abdominis plane (TAP) block for relieving acute pain after laparoscopic hernia repair as T10-L1 nerve endings are anesthetized with this block. METHODS: Seventy-one American Society of Anesthesiologists I to II patients, aged 18 to 65 years, undergoing unilateral/bilateral laparoscopic hernia repair were randomized to port site infiltration (control, 36) and TAP block groups (35). All patients received general anesthesia (fentanyl 2 MUg/kg intravenously at induction, 0.5 MUg/kg on 20% increase in heart rate or mean blood pressure) and paracetamol 6 hourly. Postintubation, TAP group received bilateral USG TAP block (15-20 mL 0.5% ropivacaine, maximum 3 mg/kg) with 18-G Tuohy needle. Control group had 20 to 30 mL 0.5% ropivacaine infiltrated preincision, at port sites from skin to peritoneum. Postoperative patient-controlled analgesia fentanyl was provided for 6 hours; pain was assessed using 0- to 100-mm visual analog scale (VAS) at 0, 1, 2, 4, 6, and 24 hours and telephonically at 1 week and 3 months. RESULTS: Demographic profile of the 2 groups was comparable. Significantly more number of patients required intraoperative fentanyl in the control group (24/36) than in the TAP group (13/35); VAS at rest was lower in TAP than control patients in postanesthesia care unit at 0, 2, 6, and 24 hours (median VAS TAP group: 0, 0, 0, and 0; control: 10, 20, 10, and 10; P= .002, P= .001, P= .001, and P= .006, respectively); P< .01 was considered statistically significant. TAP group had significantly lower VAS on deep breathing at 6 hours and on knee bending and walking at 24 hours and lesser patient-controlled analgesia fentanyl requirement. No significant difference in pain scores was observed at 1 week and 3 months. CONCLUSION: TAP block reduced postoperative pain up to 24 hours after laparoscopic hernia repair. PMID- 27555194 TI - Effects of remifentanil, nitroglycerin, and sevoflurane on the corrected QT and Tp-e intervals during controlled hypotensive anesthesia. PMID- 27555195 TI - Bivalirudin anticoagulation for minimal invasive transapical transcatheter aortic valve replacement in a patient with antiphospholipid antibodies. AB - The occurrence of lupus anticoagulant is associated with the hazard of developing an antiphospholipid syndrome, a severe prothrombotic condition which may particularly occur after major surgical trauma. This disease requires certain considerations regarding surgical strategy and anticoagulation management. We describe the perioperative management of a patient scheduled for elective aortic valve replacement and diagnosed for having antiphospholipid antibodies. The procedure was successfully performed using a minimally invasive approach via transapical aortic valve replacement and anticoagulation with the nonreversible short-acting direct thrombin Inhibitor bivalirudin. PMID- 27555196 TI - A randomized trial of prewarming on patient satisfaction and thermal comfort in outpatient surgery. AB - STUDY OBJECTIVE: To test the primary hypothesis that forced-air prewarming improves patient satisfaction after outpatient surgery and to evaluate the effect on core temperature and thermal comfort. DESIGN: Prospective randomized controlled trial. SETTING: Preoperative area, operating room, and postanesthesia care unit. PATIENTS: A total of 115 patients aged 18 to 75 years with American Society of Anesthesiologists status <4 and body mass index of 15 to 36kg/m(2) who were undergoing outpatient surgery (duration <4 hours). INTERVENTIONS: Patients were randomized to active prewarming with a Mistral-Air warming system initially set to 43 degrees C or no active prewarming. All patients were warmed intraoperatively. MEASUREMENTS: Demographic and morphometric characteristics, perioperative core temperature, ambient temperature, EVAN-G satisfaction score, thermal comfort via visual analog scales. MAIN RESULTS: Data from 102 patients were included in the final analysis. Prewarming did not significantly reduce redistribution hypothermia, with prewarmed minus not prewarmed core temperature differing by only 0.18 degrees C (95% confidence interval [CI], -0.001 to 0.37) during the initial hour of anesthesia (P=.052). Prewarming increased the mean EVAN-G satisfaction score, although not significantly, with an overall difference (prewarmed minus not prewarmed) of 5.6 (95% CI, -0.9 to 12.2; P=.09). Prewarming increased thermal comfort, with an overall difference of 6.6 mm (95% CI, 1.0 12.9; P=.02). CONCLUSION: Active prewarming increased thermal comfort but did not significantly reduce redistribution hypothermia or improve postoperative patient satisfaction. PMID- 27555197 TI - The effects of caudal or intravenous dexmedetomidine on postoperative analgesia produced by caudal bupivacaine in children: a randomized controlled double blinded study. AB - STUDY OBJECTIVES: The aim of this study was to compare the effects of caudal and intravenous (IV) dexmedetomidine (1 MUg/kg) on postoperative analgesia after caudal bupivacaine in pediatric patients undergoing lower abdominal and perineal surgeries. DESIGN: A randomized controlled double-blind study. SETTING: University-affiliated teaching hospital. PATIENTS: Seventy-five American Society of Anesthesiologists I children, aged 1 to 6 years. INTERVENTION: Patients were randomly allocated to 3 groups. All patients received 1 mL/kg caudal 0.25% bupivacaine. In addition, those in group B (n=25) received 10-mL IV saline, those in group B-Dcau (n=25) received 1 MUg/kg caudal dexmedetomidine and 10-mL IV saline, and those in group B-DIV (n=25) received 1 MUg/kg IV dexmedetomidine in 10-mL saline. MEASUREMENTS: Intraoperative mean blood pressure, heart rate, peripheral oxygen saturation, end-tidal sevoflurane, and bispectral index as well as postoperative pain and behavior scores and time to first analgesia were assessed. MAIN RESULTS: Group B-Dcau had a significantly longer time to first rescue analgesia than groups B-DIV and B, with mean (SD) values of 14.4 (7.5), 9.18 (2.7), and 6.6 (2.5) hours, respectively (P<.05). Fewer patients in group B Dcau (n=16) required rescue analgesia during the first 24 hours postoperatively compared to group B (n=24) and group B-DIV (n=20) (P<.05). Groups B-Dcau and B DIV had lower pain and behavior scores than Group B. Eight patients Group B had agitation compared to 2 in Group B-DIV and 0 in Group B-Dcau. Four patients in Group B-DIV developed bradycardia and hypotension during surgery. CONCLUSIONS: Compared to IV administration, caudal administration of dexmedetomidine during caudal bupivacaine anesthesia provided prolonged postoperative analgesia and a greater analgesic sparing effect without significant side effects. This suggests a greater role of neuraxial compared to that of peripheral alpha-2 adrenoceptors in pain processing. PMID- 27555198 TI - Randomized study of postcesarean analgesia with intrathecal morphine alone or combined with clonidine. AB - STUDY OBJECTIVE: To investigate the efficacy of the combination of intrathecal morphine with clonidine in comparison with 2 doses of intrathecal morphine alone for postcesarean analgesia. DESIGN: Prospective, double-blinded, randomized clinical trial. SETTING: Maternity ward of Hospital Santa Cruz, Curitiba, Parana, Brazil (operating room and ward). PATIENTS: The study included 195 American Society of Anesthesiologist I to III singleton parturients undergoing elective cesarean section. INTERVENTIONS: The patients were randomized into 3 groups (M50, M100, and M/C). Patients were anesthetized intrathecally with 12 mg of 0.5% hyperbaric bupivacaine and 50 MUg or 100 MUg morphine (groups M50 and M100, respectively) or 50 MUg morphine and 75 MUg clonidine (group M/C). MEASUREMENTS: The patients were subsequently assessed for pain levels and side effects at 9 to 11 hours and 22 to 24 hours after the injection. MAIN RESULTS: There was no difference in the quality of pain relief among the groups. In all 3 groups, pain was more intense during the first assessment. Pruritus and nausea were more frequent in group M100, and dizziness was more frequent in group M/C; however, these results were statistically insignificant. The group receiving clonidine showed a significantly lower incidence of shivering compared with the other groups. CONCLUSIONS: At these doses, there was no benefit of associating clonidine with morphine to improve postcesarean analgesia. Considering that higher doses of morphine were associated with more side effects, 50 MUg of intrathecal morphine alone seems to be a better option for analgesia. The use of clonidine to reduce postoperative shivering must be balanced against the potential risks of hypotension, bradycardia, dizziness, and sedation. PMID- 27555199 TI - General anesthesia in a patient with citrullinemia using Precedex as an adjunct to prevent delayed emergence. AB - Citrullinemia type I is a rare autosomal recessive genetic condition that causes reduced activity of the enzyme, argininosuccinate synthase, which is needed for proper urea metabolism. The end result is hyperammonemia which can cause life threatening neurologic symptoms and global developmental delay. Previous case reports of the anesthetic management of patients with citrullinemia describe delayed recovery possibly related to elevated ammonia levels postoperatively or choice of intraoperative anesthetics which have included narcotics. In this case report, we present the anesthetic management of a 16-year-old adolescent girl with citrullinemia type I undergoing a vagus nerve stimulator revision. We used the alpha-2-adrenergic agonist, dexmedetomidine, as an adjunct to avoid narcotics to prevent delayed emergence. She was admitted for hydration the night before the procedure and had a baseline ammonia level of 33 MUmol/L (reference, 9-33 MUmol/L). Anesthetic maintenance consisted of 2% sevoflurane, dexmedetomidine 0.5 MUg/kg per hour, and intravenous acetaminophen given toward the conclusion of the surgery. The patient awoke immediately at the end of the procedure and was extubated in the operating room. Postprocedure, her ammonia level was less than 9 MUmol/L. She appeared to be free of pain, was tolerating gastric tube feeds postprocedure, and was discharged to home on the day of surgery. Effective management of ammonia levels in this patient using preoperative hydration and dexmedetomidine as an adjunct to general anesthesia may have helped to prevent delayed emergence. PMID- 27555200 TI - Pediatric-sized laryngeal mask airway as a backup device for airway rescue: a possible choice for adult "cannot ventilate, cannot intubate" scenarios? PMID- 27555201 TI - Ultrasound-guided airway blocks using a curvilinear probe. AB - We describe a novel technique of real-time ultrasound-guided superior laryngeal nerve and translaryngeal blocks in 4 patients with anticipated difficult airways. All patients had altered neck anatomy, and 1 had a prior unsuccessful awake fiberoptic bronchoscopic intubation. For block performance, an 11-mm broadband curved array transducer with a scanning frequency between 8 and 5 MHz (Sonosite, Bothell, WA) was used for anatomical structure identification, needle guidance toward each superior laryngeal nerve and through the cricothyroid membrane, and deposition of local anesthetic in the appropriate location. This was followed by successful awake fiberoptic bronchoscopic endotracheal intubation in all cases. PMID- 27555202 TI - Bilateral breast cancer resection performed under the bilateral transversus thoracic muscle plane block. PMID- 27555203 TI - Ultrasound-guided single- vs double-level thoracic paravertebral block for postoperative analgesia in total mastectomy with axillary clearance. AB - OBJECTIVES: Thoracic paravertebral block (TPVB) for breast surgery reduces acute and chronic postoperative pain. Using ultrasound for administering the block makes it easier, with its administration at multiple levels decreasing the number of unblocked segments. We conducted this study to evaluate the efficacy and safety of single- vs double-level ultrasound-guided TPVB in patients undergoing total mastectomy with axillary clearance under general anesthesia. DESIGN: This is a prospective, randomized study. SETTING: Recovery room and operation theater. PATIENTS: Sixty ASA I and II patients, aged 18 to 60 years, who were scheduled to undergo total mastectomy with axillary clearance under general anesthesia were enrolled in the study. INTERVENTIONS: Patients received either single- (group S) or double-level (group D) ultrasound-guided TPVB at T4 or at T2 and T5 levels, respectively, using 0.3 mL/kg of 0.5% ropivacaine. MEASUREMENTS: Primary outcome measure was 24-hour analgesic consumption, and secondary outcomes included number of segments blocked, postoperative pain scores, time to first request for rescue analgesic, and any side effects. RESULTS: The mean total amount of rescue analgesic given in group S was 175.3 +/- 70 mg and in group D was 115.7 +/- 48 mg (P = .002). Median number of segments showing less sensation to pinprick was 3 in group S and 4 in group D (P < .001). The mean time to first request for rescue analgesic was 533 +/- 124 minutes in group S and was 611 +/- 214 minutes in group D (P = .118). CONCLUSION: Patients receiving double-level TPVB had significantly less 24-hour analgesic consumption in the postoperative period than those in the single-level TPVB group. This could be due to decreased pain sensation to pinprick in significantly greater number of segments in the double-level TPVB group. PMID- 27555204 TI - Cuffed endotracheal tubes in neonates and infants undergoing cardiac surgery are not associated with airway complications. AB - STUDY OBJECTIVE: To determine the incidence of postoperative airway complications in infants <5kg in weight undergoing cardiac surgery intubated with Microcuff (Kimberley-Clark, Roswell, GA) endotracheal tubes (ETTs). DESIGN: Retrospective review of infants weighing <5.0 kg with congenital heart disease (CHD) presenting for cardiac surgery. SETTING: Single-center, tertiary pediatric cardiac critical care unit at a university hospital. PATIENTS: A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013. INTERVENTION: Intubation with Microcuff (Kimberley-Clark) ETTs. STUDY DESIGN: Retrospective review of infants weighing <5.0 kg with CHD presenting for cardiac surgery to a single center tertiary care university hospital. MEASUREMENTS: Perioperative data were collected. Primary outcome was development of tracheal stenosis and/or reintubation for stridor. Stridor was defined as mild (<=2 doses of racemic epinephrine), moderate (>2 doses of racemic epinephrine), or severe (requiring reintubation). Secondary outcomes were variables possibly contributing to postextubation stridor. Infants with a tracheostomy, airway anomalies, and death prior to initial extubation were excluded. Logistic regression analysis was performed to evaluate the association between clinical risk factors and the incidence of postextubation stridor. RESULTS: A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013; 12 subjects were excluded for death prior to initial extubation. No infant developed tracheal stenosis. The incidence of any stridor was 20.9% (95% confidence interval, 15.8%-27.1%) with severe stridor in 2 cases (1%). Age at surgery, weight, duration of intubation, dexamethasone use, and ETT size were not significantly associated with postextubation stridor. Presence of a comorbidity was significantly associated with stridor (P=.01). CONCLUSIONS: Microcuff ETTs in infants <5.0 kg in weight undergoing cardiac surgery are associated with a low incidence of severe postextubation stridor. Because cuffed ETTs allow for improved control of ventilation/oxygenation and decreased risk of aspiration, they should be considered for use in this high-risk population. Larger studies are needed to confirm these results. PMID- 27555205 TI - Total intravenous anesthesia with propofol is associated with a lower rate of postoperative delirium in comparison with sevoflurane anesthesia in elderly patients. AB - STUDY OBJECTIVE: Postoperative delirium (POD) is a common complication of anesthesia. The incidence of POD in elderly patients ranges from 37% to 53%, and POD increases the morbidity and mortality of elderly patients. However, the effects of anesthetics on POD are not well known. The present study aimed to compare the incidence of POD resulting from propofol and sevoflurane anesthesia. DESIGN: Double-blind prospective study. SETTING: Operating room and postoperative recovery area. PATIENTS: Thirty patients in the sevoflurane anesthesia group and 29 in the propofol anesthesia group. MEASUREMENTS: Statistical analyses were performed using Microsoft Excel 2010 for Windows 7 (Microsoft Corporation, Redmond, Wash). Statistical analysis was performed using Fisher exact test and Student t test. MAIN RESULTS: The incidence of POD in the propofol anesthesia (6.9%) was significantly less than that observed in the sevoflurane anesthesia (26.7%; 038). CONCLUSION: In comparison with sevoflurane anesthesia, propofol anesthesia is associated with a lower incidence of POD in elderly patients. PMID- 27555206 TI - Addition of buprenorphine to local anesthetic in adductor canal blocks after total knee arthroplasty improves postoperative pain relief: a randomized controlled trial. AB - BACKGROUND AND OBJECTIVES: For the hundreds of thousands of patients who undergo total knee arthroplasty (TKA) in the United States each year, early mobilization has been demonstrated to improve functional outcomes and reduce complications. Management of postoperative pain is a critical factor in achieving early mobilization. Recent studies have shown that the use of an adductor canal block (ACB) after TKA results in increased preservation of quadriceps muscle strength, without significant difference in postoperative pain when compared to femoral nerve block. This increased preservation of quadriceps muscle strength leads to earlier mobilization. Studies have also demonstrated a prolongation of analgesia with the addition of buprenorphine to local anesthetic for regional block placement. This study examined the effect on postoperative opioid consumption when adding buprenorphine to an ACB vs an ACB with local anesthetic alone, for postoperative analgesia after unilateral TKA. METHODS: A total of 100 patients scheduled for TKA were randomized to receive postoperative ACB with local anesthetic alone or with local anesthetic and buprenorphine. The primary outcome examined was total opioid analgesic (milligrams of hydrocodone equivalent) consumption in the first 24 hours postsurgery. The secondary outcomes examined were the reported incidence of the opioid side effects nausea, vomiting, and pruritis. RESULTS: Postoperative opioid consumption decreased significantly in the group that received an ACB with local anesthetic and buprenorphine compared to an ACB with local anesthetic only (25.34+/-2.62 vs 35.84+/-2.86; P=.0076). Secondary outcomes showed no statistical difference between the 2 groups in terms of the incidence of nausea, vomiting, or pruritus. CONCLUSION: The addition of buprenorphine to an adductor canal block decreases postoperative opioid consumption when compared to an ACB with local anesthetic alone. This reduction in opioid consumption, without significant increase in side effects, makes this an attractive anesthetic adjunct for TKA. PMID- 27555207 TI - Disseminated Staphylococcus aureus infection following spinal anesthesia: a case report. AB - We here presented a 65-year-old woman with disseminated Staphylococcus aureus infection following spinal anesthesia. The patient underwent spinal anesthesia for great saphenous vein stripping. Twenty days after the procedure, the patient developed hydrocephalus, pulmonary infection, and epidural abscess. Microbiological culture of the pus showed infection by S aureus. Appropriate antibiotic therapy and prompt surgical abscess drainage were associated with good outcome. Hydrocephalus is thought to be associated with arachnoiditis caused by S aureus infection, which provides new insights into the pathophysiology of arachnoiditis. Here we reported a case of disseminated S aureus infection following spinal anesthesia, implicating that appropriate interventions should not be delayed for waiting for the microbiological results. PMID- 27555208 TI - VivaSight: a new era in the evolution of tracheal tubes. AB - STUDY OBJECTIVE: To evaluate the available data describing the use of single and double lumen VivaSight tubes. DESIGN: Systematic review. SETTING: The use of VivaSight tubes for elective surgeries including advantages, disadvantages, and possible complications. PATIENTS: Systematic review of randomized controlled trials from databases including Medline, Web of Knowledge, Google Scholar, and Cochrane Central Register of Controlled Trials. INTERVENTIONS: Comparison of VivaSight single and double-lumen tubes with conventional tubes during normal airway and expected difficult airway management. The effectiveness of the devices was also evaluated during 1-lung ventilation for patients undergoing thoracic surgery. MEASUREMENTS: Intubation time, success rate, the requirement for fiberoptic bronchoscope, and the rate of complications. MAIN RESULTS: Following a VivaSight double-lumen tube, a flexible bronchoscope is still needed. It is difficult to agree that VivaSight tube reduces the need or use of a bronchoscope. According to the current literature, it is unclear if there is any advantage of the VivaSight compared with using flexible bronchoscopy to direct a blocker into the correct lung. The cost may be another issue. Studies comparing VivaSight tubes with standard double lumen tubes reported faster tracheal intubation rate and higher success rate at first attempt for VivaSight. However, VivaSight tubes may cause soft tissue trauma such as bleeding, hematoma, edema, and erythema. Sore throat and dysphonia are other reported complications. Due to the outer thickness, smaller-sized double-lumen tube may be necessary. It has been reported to have the disadvantages, such as melting due to the heat of light source before insertion and sudden shutdown without warning. CONCLUSIONS: Problems such as overheating and melting on the distal end of the tube due to the light source and potential breakdowns of the cable should be solved by the manufacturer. This will probably require a redesign and necessitate further studies. PMID- 27555209 TI - Use of single-lumen tube for minimally invasive and hybrid esophagectomies with prone thoracoscopic dissection: case series. AB - Minimally invasive and hybrid minimally invasive esophagectomy (MIE) is a technically challenging procedure. Anesthesia for the same is equally challenging due to special requirements of the video-assisted thoracoscopic technique used and shared operative and respiratory fields. Standard ventilatory strategy for this kind of surgery has been 1-lung ventilation with the help of a double-lumen tube. Prone positioning for thoracoscopic dissection facilitates gravity dependant collapse of the operative side lung induced by a unilateral capnothorax, thus making the use of single-lumen endotracheal tube a feasible option for this surgery. We report our experience of 10 consecutive cases of minimally invasive esophagectomy conducted in prone position at our center and the use of single-lumen endotracheal tube for ventilation. PMID- 27555210 TI - Interventional and multimodal pain rehabilitation in a child with meralgia paresthetica. AB - Meralgia paresthetica is a chronic pain syndrome that is extremely rare in the pediatric population. It is manifested by hypesthesia or pain in the distribution of the lateral femoral cutaneous nerve (LFCN) and is typically caused by entrapment as the nerve passes deep to the inguinal ligament. This sensory mononeuropathy is rare in children and diagnosis is typically delayed, often leading to prolonged functional impairment and unnecessary medical testing. A 9 year-old girl presented to the pain clinic with a 6-week history of right anterolateral thigh pain first noticed after a nontraumatic cheerleading practice. Comprehensive laboratory and radiographic evaluation by multiple prior specialists revealed no clear nociceptive source of pain. History and examination were consistent with a diagnosis of idiopathic, compressive meralgia paresthetica. Conservative management including physical therapy was followed for 2 weeks with only mild improvement noted. To facilitate physical therapy, an ultrasound-guided LFCN block was performed which confirmed the diagnosis by providing complete analgesia. The patient reported overall 25% improvement from multimodal therapy at another 2 weeks. A second LFCN block was performed with complete resolution of symptoms and restoration of function. The patient remains pain-free and has returned to walking, running, and competitive sports. The primary goal of pediatric chronic pain management, regardless of pain etiology, is early restoration of function to avoid prolonged absence from school, sports, or other productive activities and limit the psychological burden of chronic disease. PMID- 27555211 TI - Evaluation of high-risk obstetric patients: a survey of US academic centers. AB - STUDY OBJECTIVES: Obstetric anesthesiologists commonly care for high-risk obstetric patients. However, it is unclear how obstetricians refer these patients for anesthetic evaluation and whether obstetric anesthesia clinics (OACs) are used. Our study aims were to determine the availability and characteristics of OACs at US academic obstetric centers and to evaluate how high-risk patients are referred for anesthetic evaluation. DESIGN: This is a survey study design. SETTING: University of Virginia Center for Survey Research. INTERVENTION: A survey questionnaire was constructed and electronically mailed to obstetric anesthesia directors based at hospitals with accredited anesthesia residency programs. MEASUREMENT: One hundred thirteen obstetric anesthesia directors were contacted. We asked questions about the presence and operational characteristics of OACs. These characteristics were compared between hospitals with high, medium, and low annual delivery volumes. We also inquired about how high-risk patients are referred for anesthetic evaluation. Frequencies were compared using Fisher test, with P< .05 considered as statistically significant. MAIN RESULTS: The survey response rate was 58% (n = 65). Overall, only 25 (38%) respondents indicated that their hospital operated an OAC. The proportion of hospitals with an OAC and OAC operational hours did not significantly vary according to hospital delivery volume. Among hospitals with an OAC, 24% respondents indicated that obstetricians always refer high-risk patients to the OAC. Nearly half of respondents (44%) indicated that high-risk patients usually or sometimes receive their first anesthetic evaluation during the delivery hospitalization. CONCLUSION: Our findings suggest that, among US academic centers, OACs are uncommon and the referral of high-risk patients for antenatal anesthetic evaluation is inconsistent. These findings suggest that more structured referral processes are needed to ensure that high-risk women receive anesthetic evaluation before labor or delivery. PMID- 27555212 TI - Does laryngoscopic view after intubation predict laryngoscopic view before intubation? AB - STUDY OBJECTIVE: To determine if an endotracheal (ET) tube will distort the laryngeal view obtained with direct laryngoscopy measuring with the modified Cormack-Lehane scale (MCL). DESIGN: Observational single-arm study. SETTING: The University of Calgary teaching hospitals. PATIENTS: Patients between 18 and 86 years of age undergoing elective surgical procedures. A total of 173 patients were enrolled and analyzed. INTERVENTIONS: Direct laryngoscopy view obtained before ET intubation and directly after intubation. MEASUREMENTS AND RESULTS: The MCL scales were described for each view obtained and compared to each other with each patient serving as their own control. The primary objective was a change in the best obtainable view by direct laryngoscopy from an acceptable view (MCLS 1 or 2a) to an unacceptable view (MCLS 2b, 3, or 4) or changing from an unacceptable view (MCLS 2b, 3, or 4) to an acceptable view (MCLS 1 or 2a). The main finding of this study was that the ET tube altered the MCL in 58 (33%) of 173 patients, "worsening" the grade in 30 patients (17.34%) and "improving" the grade in 28 patients (16.18%). CONCLUSIONS: We performed a prospective observational study to address the predictive value of postintubation laryngoscopy grade in adults. The presence of the ET tube both increased visualization of the glottis and worsened the view in different subjects. The important outcome was that the presence of the ET tube did in fact change the view obtained of the larynx during direct laryngoscopy. In conclusion, postintubation MCL grades may not be reliable to predict laryngeal grade and should be used with caution in the right clinical context. PMID- 27555213 TI - Preoperative exercise therapy in surgical care: a scoping review. AB - OBJECTIVES: Several systematic reviews have focused on the role of preoperative exercise therapy (PET) in various fields of surgical care. Aims of the present scoping review are to summarize research findings and to identify gaps in existing literature. METHODS: Two authors independently conducted a comprehensive literature search on systematic reviews regarding PET. The risk of bias was assessed using "the methodology checklist for systematic reviews and meta analyses of the Scottish Intercollegiate Guidelines Network (SIGN)." Findings of the included systematic reviews were summarized according to type of surgery and type of PET. RESULTS: Twenty-one reviews on PET with a low risk of bias were included. Seven reviews investigated PET in multiple surgical fields and 14 in just a single surgical field. PET was studied before cardiac surgery (n = 9), orthopedic surgery (n = 8), abdominal surgery (n = 8), thoracic surgery (n = 8), vascular surgery (n = 3), and urologic surgery (n = 1). CONCLUSION: Overall, it seems that PET exerts beneficial effects on physical fitness and postoperative outcome measures. Gaps in current literature are the heterogeneity in selected patient populations and outcome measures as well as lack of guidelines on the specific PET regimes. Therefore, there is increasing need for multicenter randomized trials with specifically designed PET programs and a carefully selected patient population to strengthen current evidence. PMID- 27555214 TI - Effect of prolonged-released oxycodone/naloxone in postoperative pain management after total knee replacement: a nonrandomized prospective trial. AB - PURPOSE: The purpose of this study was to examine the effect of postoperative prolonged release oxycodone/naloxone (OXN) in comparison to other opioids (control group) on the early postoperative rehabilitation outcome after total knee replacement. METHODS: In a prospective, noninterventional, nonrandomized clinical trial, 80 patients were assigned to either the OXN group or a control group. Postoperative outcome and pain level at days 3, 6, 21, 35, and 6months were evaluated using the Bowel Function Index, Brief Pain Inventory Short Form questionnaire, the Hospital for Special Surgery score, modified Larson score, and the ability to attend physiotherapy. Medications were recorded and safety analysis was done. Both groups were compared using an analysis of covariance. RESULTS: There were no significant differences between both groups regarding pain levels. OXN group patients reported better bowel function (median values of 0.0 for the OXN group and 20.0 for the control group). No effect of treatment group (P=.19) and no treatment-by-visit interaction on Hospital for Special Surgery final score (P=.67) could be detected, but Larson function score in the early postoperative phase was significantly better in the OXN group (P=.018). The proportion of OXN group patients who were able to attend without any restriction was 58.1%. The proportions of patients in the OXN group and control group who experienced mild or moderate adverse drug reactions were 23.3% and 37.8%, respectively. There were no serious adverse drug reactions. CONCLUSION: In conclusion, OXN provides an effective analgesia and offers several benefits such as higher ability to participate in physiotherapy and better functional results. Incidence and severity of constipation can be reduced by using prolonged-released OXN as compared with other opioids. PMID- 27555215 TI - Lysozyme activity of the Ruminococcus champanellensis cellulosome. AB - Ruminococcus champanellensis is a keystone species in the human gut that produces an intricate cellulosome system of various architectures. A variety of cellulosomal enzymes have been identified, which exhibit a range of hydrolytic activities on lignocellulosic substrates. We describe herein a unique R. champanellensis scaffoldin, ScaK, which is expressed during growth on cellobiose and comprises a cohesin module and a family 25 glycoside hydrolase (GH25). The GH25 is non-autolytic and exhibits lysozyme-mediated lytic activity against several bacterial species. Despite the narrow acidic pH curve, the enzyme is active along a temperature range from 2 to 85 degrees C and is stable at very high temperatures for extended incubation periods. The ScaK cohesin was shown to bind selectively to the dockerin of a monovalent scaffoldin (ScaG), thus enabling formation of a cell-free cellulosome, whereby ScaG interacts with a divalent scaffodin (ScaA) that bears the enzymes either directly or through additional monovalent scaffoldins (ScaC and ScaD). The ScaK cohesin also interacts with the dockerin of a protein comprising multiple Fn3 domains that can potentially promote adhesion to carbohydrates and the bacterial cell surface. A cell-free cellulosomal GH25 lysozyme may provide a bacterial strategy to both hydrolyze lignocellulose and repel eventual food competitors and/or cheaters. PMID- 27555216 TI - Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/beta-catenin signaling associated mechanism. AB - Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/beta-catenin signaling. PEMF stimulated group exhibited higher Runx2, Wnt1, Lrp6 and beta-catenin protein expressions. In vivo results via MUCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/beta-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/beta-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect. PMID- 27555217 TI - Metamaterial-enhanced vibrational absorption spectroscopy for the detection of protein molecules. AB - From visible to mid-infrared frequencies, molecular sensing has been a major successful application of plasmonics because of the enormous enhancement of the surface electromagnetic nearfield associated with the induced collective motion of surface free carriers excited by the probe light. However, in the lower-energy terahertz (THz) region, sensing by detecting molecular vibrations is still challenging because of low sensitivity, complicated spectral features, and relatively little accumulated knowledge of molecules. Here, we report the use of a micron-scale thin-slab metamaterial (MM) architecture, which functions as an amplifier for enhancing the absorption signal of the THz vibration of an ultrathin adsorbed layer of large organic molecules. We examined bovine serum albumin (BSA) as a prototype large protein molecule and Rhodamine 6G (Rh6G) and 3,3'-diethylthiatricarbocyanine iodide (DTTCI) as examples of small molecules. Among them, our MM significantly magnified only the signal strength of bulky BSA. On the other hand, DTTCI and Rh6G are inactive, as they lack low-frequency vibrational modes in this frequency region. The results obtained here clearly demonstrate the promise of MM-enhanced absorption spectroscopy in the THz region for detection and structural monitoring of large biomolecules such as proteins or pathogenic enzymes. PMID- 27555218 TI - Density functional theory for molecular and periodic systems using density fitting and continuous fast multipole method: Analytical gradients. AB - A full implementation of analytical energy gradients for molecular and periodic systems is reported in the TURBOMOLE program package within the framework of Kohn Sham density functional theory using Gaussian-type orbitals as basis functions. Its key component is a combination of density fitting (DF) approximation and continuous fast multipole method (CFMM) that allows for an efficient calculation of the Coulomb energy gradient. For exchange-correlation part the hierarchical numerical integration scheme (Burow and Sierka, Journal of Chemical Theory and Computation 2011, 7, 3097) is extended to energy gradients. Computational efficiency and asymptotic O(N) scaling behavior of the implementation is demonstrated for various molecular and periodic model systems, with the largest unit cell of hematite containing 640 atoms and 19,072 basis functions. The overall computational effort of energy gradient is comparable to that of the Kohn Sham matrix formation. (c) 2016 Wiley Periodicals, Inc. PMID- 27555219 TI - B0 mapping using rewinding trajectories (BMART). AB - PURPOSE: To create a B0 map and correct for off-resonance with minimal scan time increase for two-dimensional (2D) or 3D non-Cartesian acquisitions. METHODS: Rewinding trajectories that bring the zeroth gradient moment to zero every repetition time (TR) were used to estimate the off-resonance with a center-out 3D cones trajectory, which required an increase in the minimum TR by 5%. The off resonance estimation and correction was implemented using an algorithm based on binning and object-domain phase correction. B0 maps using BMART (B0 mapping using rewinding trajectories) were compared to maps obtained using separate scans with multiple echo time (TE) in a phantom and human brain. RESULTS: Excellent agreement between BMART and the multiple-TE method were observed, and images corrected with BMART were deblurred. CONCLUSION: BMART can correct for off resonance without requiring an additional scan, and can be easily applied to center-out or projection trajectories (2D or 3D). Magn Reson Med 78:664-669, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27555221 TI - Does Acupuncture Alter Pain-related Functional Connectivity of the Central Nervous System? A Systematic Review. AB - Acupuncture has been studied for several decades to establish evidence-based clinical practice. This systematic review aims to evaluate evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain. A systematic search of the literature was conducted to identify studies in which the central response of acupuncture in patients with musculoskeletal pain was evaluated by neuroimaging techniques. Databases searched were AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PEDro, Pubmed, SCOPUS, SPORTDiscuss, and Web of Science. Included studies were assessed by two independent reviewers for their methodological quality by using the Downs and Black questionnaire and for their levels of completeness and transparency in reporting acupuncture interventions by using Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. Seven studies met the inclusion criteria. Three studies were randomized controlled trials (RCTs) and four studies were nonrandomized controlled trials (NRCTs). The neuroimaging techniques used were functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Positive effects on the functional connectivity of the central nervous system more consistently occurred during long-term acupuncture treatment. The results were heterogeneous from a descriptive perspective; however, the key findings support acupuncture's ability to alter pain-related functional connectivity in the central nervous system in patients with musculoskeletal pain. PMID- 27555220 TI - Understanding the spatiotemporal pattern of grazing cattle movement. AB - Understanding the drivers of animal movement is significant for ecology and biology. Yet researchers have so far been unable to fully understand these drivers, largely due to low data resolution. In this study, we analyse a high frequency movement dataset for a group of grazing cattle and investigate their spatiotemporal patterns using a simple two-state 'stop-and-move' mobility model. We find that the dispersal kernel in the moving state is best described by a mixture exponential distribution, indicating the hierarchical nature of the movement. On the other hand, the waiting time appears to be scale-invariant below a certain cut-off and is best described by a truncated power-law distribution, suggesting that the non-moving state is governed by time-varying dynamics. We explore possible explanations for the observed phenomena, covering factors that can play a role in the generation of mobility patterns, such as the context of grazing environment, the intrinsic decision-making mechanism or the energy status of different activities. In particular, we propose a new hypothesis that the underlying movement pattern can be attributed to the most probable observable energy status under the maximum entropy configuration. These results are not only valuable for modelling cattle movement but also provide new insights for understanding the underlying biological basis of grazing behaviour. PMID- 27555222 TI - Effect of Acupuncture on Pain and Quality of Life in Patients with Lumbar Spinal Stenosis: A Case Series Study. AB - Lumbar spinal stenosis (LSS) is a major cause of debilitation in adults, and acupuncture is a recommended treatment. We assessed the effect of acupuncture on pain and quality of life in patients with LSS. Twenty-four patients with LSS who had symptoms of neurogenic claudication were randomly selected and underwent 10 sessions of acupuncture. Pain and quality of life were evaluated before and immediately after the intervention and 6 weeks later using a visual analogue scale and Short Form-36 Health Survey. Paired t tests and repeated measure tests were used to analyze the data. The mean age of the patients was 48.2 +/- 10.8 years. The mean visual analogue scale scores before and immediately after intervention (7.9 +/- 1.3 and 4.3 +/- 2.1) were statistically different (p < 0.001), as was the mean score (3.08 +/- 2.3) 6 weeks later (p = 0.01). Five aspects of the Short Form-36 Health Survey score were associated with significant improvements immediately after acupuncture (p < 0.05). Comparisons of the scores before and 6 weeks after intervention showed significant improvements in emotions, vitality, general health, bodily pain, and physical well-being. Therefore, acupuncture had a significant short-term effect on pain and quality of life in patients with LSS. PMID- 27555223 TI - Differential Effect of Electroacupuncture on Inflammatory Adipokines in Two Rat Models of Obesity. AB - Chronic inflammation is known to be associated with visceral obesity and insulin resistance which are characterized by altered levels of production of pro- and anti-inflammatory adipokines. The dysregulation of the production of inflammatory adipokines and their functions in obese individuals leads to a state of chronic low-grade inflammation and may promote obesity-linked metabolic disorders and cardiovascular diseases such as insulin resistance, metabolic syndrome, and atherosclerosis. Electroacupuncture (EA) was tested to see if there was a difference in its effect on pro- and anti-inflammatory adipokine levels in the blood serum and the white adipose tissue of obese Zucker fatty rats and high-fat diet-induced obese Long Evans rats. In the two rat models of obesity, on Day 12 of treatment, repeated applications of EA were seen to have had a significant differential effect for serum tumor necrosis factor-alpha, adiponectin, the adiponectin:leptin ratio, and blood glucose. For the adipose tissue, there was a differential effect for adiponectin that was on the borderline of significance. To explore these changes further and how they might affect insulin resistance would require a modification to the research design to use larger group sizes for the two models or to give a greater number of EA treatments. PMID- 27555224 TI - Auricular Acupuncture Versus Progressive Muscle Relaxation in Patients with Anxiety Disorders or Major Depressive Disorder: A Prospective Parallel Group Clinical Trial. AB - Although acupuncture treatment is increasingly in demand among psychiatric patients, to date no studies have investigated the effectiveness of auricular acupuncture (AA) in treating anxiety disorders or major depressive disorder. Thus, this study aimed to compare the effectiveness of AA versus progressive muscle relaxation (PMR), a standardized and accepted relaxation method. We examined 162 patients with a primary diagnosis of anxiety disorder or major depressive disorder, and each patient chose between treatment with AA, executed according to the National Acupuncture Detoxification Association protocol, and treatment with PMR. Each group had treatments twice a week for 4 weeks. Before and after treatment, each participant rated four items on a visual analog scale: anxiety, tension, anger/aggression, and mood. Statistical analyses were performed with the original visual analog scale scores and the Change-Intensity Index, an appropriate indicator of the difference between two values of a variable. Our results show that treatment with AA significantly decreased tension, anxiety, and anger/aggression throughout the 4 weeks, but did not elevate mood. Between AA and PMR, no statistically significant differences were found at any time. Thus, we suggest that both AA and PMR may be useful, equally-effective additional interventions in the treatment of the above-mentioned disorders. PMID- 27555225 TI - 100-Hz Electroacupuncture but not 2-Hz Electroacupuncture is Preemptive Against Postincision Pain in Rats. AB - Preemptive analgesia involves introducing an analgesic before noxious stimulation. Electroacupuncture (EA) activates descending mechanisms that modulate nociceptive inputs into the spinal dorsal horn. This study evaluated whether preoperative EA is more effective than postoperative EA in reducing incision pain in rats. The nociceptive threshold to mechanical stimulation was utilized to examine the effects of an intraperitoneal injection of saline (0.1 mL/kg) or naloxone (1 mg/kg) on antinociception induced by a 20-minute period of 2-Hz or 100-Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints before surgical incision, or 10 minutes after or 100 minutes after surgical incision of the hind paw. The extent of mechanical hyperalgesia after the incision was significantly attenuated by the application of 100-Hz EA preoperatively, but not by its application at 10 minutes or 100 minutes postoperatively. By contrast, 2-Hz EA was effective against postoperative hyperalgesia when applied 10 minutes or 100 minutes after surgery but not when it was applied preoperatively. Only the effect of 2-Hz EA applied 10 minutes after surgery was sensitive to naloxone. The present study showed for the first time that 100-Hz EA, but not 2-Hz EA, exerts a nonopioidergic preemptive effect against postincision pain in rats. PMID- 27555226 TI - Phytochemical Profile of Erythrina variegata by Using High-Performance Liquid Chromatography and Gas Chromatography-Mass Spectroscopy Analyses. AB - Natural products derived from plant sources have been utilized to treat patients with numerous diseases. The phytochemical constituents present in ethanolic leaf extract of Erythrina variegata (ELEV) were identified by using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectroscopy (GC-MS) analyses. Shade dried leaves were powdered and extracted with ethanol for analyses through HPLC to identify selected flavonoids and through GC-MS to identify other molecules. The HPLC analysis of ELEV showed the presence of gallic and caffeic acids as the major components at concentrations of 2.0 ppm and 0.1 ppm, respectively, as well as other components. GC-MS analysis revealed the presence of 3-eicosyne; 3,7,11,15-tetramethyl-2-hexadecen-1-ol; butanoic acid, 3 methyl-3,7-dimethyl-6-octenyl ester; phytol; 1,2-benzenedicarboxylic acid, diundecyl ester; 1-octanol, 2-butyl-; squalene; and 2H-pyran, 2-(7 heptadecynyloxy) tetrahydro-derivative. Because pharmacopuncture is a new evolving natural mode that uses herbal extracts for treating patients with various ailments with minimum pain and maximum effect, the results of this study are particularly important and show that ELEV possesses a wide range of phytochemical constituents, as indicated above, as effective active principle molecules that can be used individually or in combination to treat patients with various diseases. PMID- 27555227 TI - Yoga for Health Care in Korea: A Protocol for Systematic Review of Clinical Trials. AB - This systematic review aims to evaluate the therapeutic effects of yoga therapy using an evidence-based approach and investigates the relationship between yoga and the meridian energies based on all available clinical studies in Korea. Sixteen electronic databases will be searched from the inception of the study until January 2016. All clinical evidences that evaluate any type of yoga and any type of control in individuals with any type of condition will be eligible. The methodological quality will be assessed using the Cochrane risk of bias tool for randomized clinical trials and the Newcastle-Ottawa scale for nonrandomized studies. Two authors will independently assess each study for eligibility and the risk of bias, and then they will extract the data. With its extensive, unbiased search of the Korean literature from various databases without any language restrictions, this systematic review will be useful for both practitioners in the field of yoga research as well as for patients. PMID- 27555228 TI - Image Guided Adaptive Brachytherapy in cervix cancer: A new paradigm changing clinical practice and outcome. PMID- 27555229 TI - Fiducial marker guided stereotactic liver radiotherapy: Is a time delay between marker implantation and planning CT needed? AB - To minimize the risk of marker migration in fiducial marker guided liver SBRT it is common to add a delay of a week between marker implantation and planning CT. This study found that such a delay is unnecessary and could be avoided to minimize the treatment preparation time. PMID- 27555230 TI - Role of mechanistic target of rapamycin (mTOR) in renal function and ischaemia reperfusion induced kidney injury. AB - Despite the presence of many studies on the role of mechanistic target of rapamycin (mTOR) in cardiorenal tissues, the definitive role of mTOR in the pathogenesis of renal injury subsequent to ischaemia-reperfusion (IR) remains unclear. The aims of the current study were to characterize the role of mTOR in normal kidney function and to investigate the role of mTOR activation in IR induced kidney injury. In euvolemic anaesthetized rats, treatment with the mTOR inhibitor rapamycin increased blood pressure (121 +/- 2 to 144 +/- 3 mmHg; P<.05), decreased glomerular filtration rate (GFR; 1.6 +/- 0.3 to 0.5 +/- 0.2 mL/min; P<.05) and increased urinary sodium excretion (UNaV; 14 +/- 1 to 109 +/- 25 mmol/L per hour; P<.05). In rats subjected to IR, autophagy induction, p-mTOR expression and serum creatinine increased (1.9 +/- 0.2 to 3 +/- 0.3 mg/dL; P<.05); treatment with rapamycin blunted p-mTOR expression but further increased autophagy induction and serum creatinine (3 +/- 0.3 to 5 +/- 0.6 mg/dL; P<.05). In contrast, clenbuterol, an mTOR activator, blunted the effect of rapamycin on serum creatinine (4 +/- 0.6 vs 2.3 +/- 0.3 mg/dL; P<.05), autophagy induction and p-mTOR expression. IR also increased 24 hour protein excretion (9 +/- 3 to 17 +/- 2 mg/day; P<.05) and kidney injury molecule-1 (KIM-1) expression, and rapamycin treatment further increased KIM-1 expression. Clenbuterol exacerbated protein excretion (13 +/- 2 to 26 +/- 4 mg/day; P<.05) and antagonized the effect of rapamycin on KIM-1 expression. Histopathological data demonstrated kidney injury in IR rats that was worsened by rapamycin treatment but attenuated by clenbuterol treatment. Thus, mTOR signalling is crucial for normal kidney function and protecting the kidney against IR injury through autophagy suppression. PMID- 27555231 TI - Molecular chaperone Hsp27 regulates the Hippo tumor suppressor pathway in cancer. AB - Heat shock protein 27 (Hsp27) is a molecular chaperone highly expressed in aggressive cancers, where it is involved in numerous pro-tumorigenic signaling pathways. Using functional genomics we identified for the first time that Hsp27 regulates the gene signature of transcriptional co-activators YAP and TAZ, which are negatively regulated by the Hippo Tumor Suppressor pathway. The Hippo pathway inactivates YAP by phosphorylating and increasing its cytoplasmic retention with the 14.3.3 proteins. Gain and loss of function experiments in prostate, breast and lung cancer cells showed that Hsp27 knockdown induced YAP phosphorylation and cytoplasmic localization while overexpression of Hsp27 displayed opposite results. Mechanistically, Hsp27 regulates the Hippo pathway by accelerating the proteasomal degradation of ubiquitinated MST1, the core Hippo kinase, resulting in reduced phosphorylation/activity of LATS1 and MOB1, its downstream effectors. Importantly, our in vitro results were supported by data from human tumors; clinically, high expression of Hsp27 in prostate tumors is correlated with increased expression of YAP gene signature and reduced phosphorylation of YAP in lung and invasive breast cancer clinical samples. This study reveals for the first time a link between Hsp27 and the Hippo cascade, providing a novel mechanism of deregulation of this tumor suppressor pathway across multiple cancers. PMID- 27555233 TI - Repetitive transcranial magnetic stimulation effectively facilitates spatial cognition and synaptic plasticity associated with increasing the levels of BDNF and synaptic proteins in Wistar rats. AB - Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique, by which cognitive deficits can be alleviated. Furthermore, rTMS may facilitate learning and memory. However, its underlying mechanism is still little known. The aim of this study was to investigate if the facilitation of spatial cognition and synaptic plasticity, induced by rTMS, is regulated by enhancing pre- and postsynaptic proteins in normal rats. Morris water maze (MWM) test was performed to examine the spatial cognition. The synaptic plasticity, including long-term potentiation (LTP) and depotentiation (DEP), presynaptic plasticity paired-pulse facilitation (PPF), from the hippocampal Schaffer collaterals to CA1 region was subsequently measured using in vivo electrophysiological techniques. The expressions of brain-derived neurotrophic factor (BDNF), presynaptic protein synaptophysin (SYP) and postsynaptic protein NR2B were measured by Western blot. Our data show that the spatial learning/memory and reversal learning/memory in rTMS rats were remarkably enhanced compared to that in the Sham group. Furthermore, LTP and DEP as well as PPF were effectively facilitated by 5Hz-rTMS. Additionally, the expressions of BDNF, SYP and NR2B were significantly increased via magnetic stimulation. The results suggest that rTMS considerably increases the expressions of BDNF, postsynaptic protein NR2B and presynaptic protein SYP, and thereby significantly enhances the synaptic plasticity and spatial cognition in normal animals. PMID- 27555232 TI - Long-term habituation of the C-start escape response in zebrafish larvae. AB - The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory. PMID- 27555234 TI - Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity. AB - Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. PMID- 27555236 TI - Fabry Disease: A Disorder of Childhood Onset. AB - BACKGROUND: Fabry disease, an X-linked disorder of glycosphingolipids, markedly increases the risk of systemic vasculopathy, ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction, and chronic kidney disease. METHODS: We performed an extensive PubMed search on the topic of Fabry disease and drew from our cumulative 43 years of experience. RESULTS: Most of these complications are nonspecific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. This disease is caused by variants of the GLA gene, and its incidence may have been underestimated. However, one must also guard against overdiagnosis of Fabry disease and unjustified enzyme replacement therapy, because some of the gene variants are benign. Specific therapy for Fabry disease has been developed in the last few years, but its clinical effect has been modest. Novel therapeutic agents are being developed. Standard "nonspecific" medical and surgical therapy is necessary and effective in slowing deterioration or compensating for organ failure in patients with Fabry disease. CONCLUSIONS: Fabry disease is a treatable and modifiable genetic risk factor for a myriad of clinical organ complications. Fabry disease may be frequently overlooked but on occasion overdiagnosed. PMID- 27555235 TI - Chronic sleep deprivation differentially affects short and long-term operant memory in Aplysia. AB - The induction, formation and maintenance of memory represent dynamic processes modulated by multiple factors including the circadian clock and sleep. Chronic sleep restriction has become common in modern society due to occupational and social demands. Given the impact of cognitive impairments associated with sleep deprivation, there is a vital need for a simple animal model in which to study the interactions between chronic sleep deprivation and memory. We used the marine mollusk Aplysia californica, with its simple nervous system, nocturnal sleep pattern and well-characterized learning paradigms, to assess the effects of two chronic sleep restriction paradigms on short-term (STM) and long-term (LTM) associative memory. The effects of sleep deprivation on memory were evaluated using the operant learning paradigm, learning that food is inedible, in which the animal associates a specific netted seaweed with failed swallowing attempts. We found that two nights of 6h sleep deprivation occurring during the first or last half of the night inhibited both STM and LTM. Moreover, the impairment in STM persisted for more than 24h. A milder, prolonged sleep deprivation paradigm consisting of 3 consecutive nights of 4h sleep deprivation also blocked STM, but had no effect on LTM. These experiments highlight differences in the sensitivity of STM and LTM to chronic sleep deprivation. Moreover, these results establish Aplysia as a valid model for studying the interactions between chronic sleep deprivation and associative memory paving the way for future studies delineating the mechanisms through which sleep restriction affects memory formation. PMID- 27555237 TI - Role of fine needle aspiration biopsy cytology in the diagnosis of infections. AB - The role of fine needle aspiration biopsy (FNAB) cytology in diagnosing infections has expanded due to the increase in the number of immune compromised patients and the increasing role of FNAB in the developing world where infection is a major cause of illness. FNAB has become the first procedural test in cases where the clinical and imaging findings suggest an infectious lesion or where there is a differential diagnosis of infection or metastatic or primary tumor. This applies to FNAB of palpable or image directed or deep seated lesions accessed by EUS and EBUS. This article details a recommended approach and technique for FNAB of infectious lesions, and discusses the role of rapid on site evaluation and the application of ancillary testing including the rapidly expanding array of molecular tests based on FNAB material. The utility of recognizing suppurative and granulomatous infectious patterns in FNAB direct smears, and the specific cytomorphological features on routine Papanicolaou and Giemsa stains and on special stains of FNAB smears is described for a large number of bacterial, fungal, viral, parasitic, and protozoan infections. The role of cytopathologists is to now train cytopathologists in sufficient numbers to provide FNAB services, teach trainee cytopathologists and cytotechnologists, and to encourage our clinical colleagues to use FNAB in the diagnosis of infections and other lesions to the benefit of patients and the medical system. Diagn. Cytopathol. 2016;44:1024-1038. (c) 2016 Wiley Periodicals, Inc. PMID- 27555238 TI - Evaluation of highly sensitive immunoassay technologies for quantitative measurements of sub-pg/mL levels of cytokines in human serum. AB - A comprehensive cross-platform and cross-assay evaluation using nine technology platforms and four cytokine immunoassays (IL-6, TNFalpha, IL-17a, IL-2) was performed by comparing assay precision, sensitivity, parallelism and data correlation between platforms. The precision was acceptable for most evaluated assays. In addition to comparing the analytical assay sensitivity using a spiked recombinant analyte in buffer, forty serum samples from both normal controls and multiple sclerosis patients were used to measure the frequency of endogenous analyte detection (FEAD) as a parameter of each assay's ability to detect the endogenous analyte. The highest FEAD measurements were observed on the SimoaTM, Erenna(r), Milliplex(r) and Imperacer(r) platforms. However, only Simoa and Erenna results showed a high correlation across all evaluated cytokine assays, followed by a more moderate correlation of results across platforms for the V plexTM, high sensitivity ELISA and the EllaTM IL-6 and TNFalpha assays. In contrast, results from the evaluated cytokine assays on the Milliplex, AMMPTM ViBE(r) and Imperacer platforms did not correlate to each other nor to other evaluated assays. Acceptable parallelism was observed for the Simoa, Erenna, V plex and Ella assays but not for the Milliplex, AMMP ViBE and Imperacer assays. In conclusion, the Simoa, Erenna,V-plex and Ella platforms performed well in one or more evaluated cytokine assays. Among those, the Simoa and Erenna assays had the highest sensitivity for detection of cytokines present at sub-pg/mL levels in human serum. In addition, the cross-platform and cross-assay comparisons demonstrated that different immunoassays may yield different results, which underscores the importance of performing such comparative evaluations, especially in the absence of reliable reference standards for the quantitative assessments of biomarkers in immunoassays. PMID- 27555239 TI - Correlation of transferrin receptor (CD71) with Ki67 expression on stimulated human and mouse T cells: The kinetics of expression of T cell activation markers. AB - T cell activation is a fascinating, yet tightly regulated cascade of events that lead to the induction of cytokine and expression of activation molecules that eventually result in divergent immune responses. Analyzing the qualitative and quantitative nature of T cell activation in different immunological conditions provides valuable information about the immune responses mediated by different agents or vaccinations. We evaluated the kinetics of CD4(+) and CD8(+) T cell activation markers such as CD25, CD38, CD69, CD71 and Ki67 following anti CD3/CD28 stimulation over a time course. Our data show that the kinetics of expression of these activation markers follows a precise and consistent time course with some differences between mouse and human T cells. Percentage of human T cells expressing CD69 and CD25 reached >90% at 24h stimulation, whereas higher percentage of cells co-expressing CD71 and Ki67 was evident for CD8(+) T cells compared with CD4(+) T cells at 24h. Similar to human T cells, percentage of CD8(+)CD38(+) cells was delayed but reached to >90% on mouse CD8(+) T cells at 48h and on mouse CD4(+) T cells at 72h. After 72h of stimulation all tested activation markers remained at the maximum levels in mouse T cells but interestingly percentages of cells expressing CD69 was significantly reduced in human T cells. Furthermore, these data demonstrate a positive correlation between CD71 and Ki67 expression on both mouse and human T cells from 12h post stimulation. Thus our results define the kinetics of activation markers/proliferation in human and mouse T cells; and may serve a reference for monitoring T cell function in clinical study and vaccinology. PMID- 27555240 TI - Effect of Inter-Porphyrin Distance on Spin-State in Diiron(III) MU-Hydroxo Bisporphyrins. AB - The synthesis, structure, and properties of bischloro, MU-oxo, and a family of MU hydroxo complexes (with BF4 (-) , SbF6 (-) , and PF6 (-) counteranions) of diethylpyrrole-bridged diiron(III) bisporphyrins are reported. Spectroscopic characterization has revealed that the iron centers of the bischloro and MU-oxo complexes are in the high-spin state (S=(5) /2 ). However, the two iron centers in the diiron(III) MU-hydroxo complexes are equivalent with high spin (S=(5) /2 ) in the solid state and an intermediate-spin state (S=(3) /2 ) in solution. The molecules have been compared with previously known diiron(III) MU-hydroxo complexes of ethane-bridged bisporphyrin, in which two different spin states of iron were stabilized under the influence of counteranions. The dimanganese(III) analogues were also synthesized and spectroscopically characterized. A comparison of the X-ray structural parameters between diethylpyrrole and ethane-bridged MU hydroxo bisporphyrins suggest an increased separation, and hence, less interactions between the two heme units of the former. As a result, unlike the ethane-bridged MU-hydroxo complex, both iron centers become equivalent in the diethylpyrrole-bridged complex and their spin state remains unresponsive to the change in counteranion. The iron(III) centers of the diethylpyrrole-bridged diiron(III) MU-oxo bisporphyrin undergo very strong antiferromagnetic interactions (J=-137.7 cm(-1) ), although the coupling constant is reduced to only a weak value in the MU-hydroxo complexes (J=-42.2, -44.1, and -42.4 cm(-1) for the BF4 , SbF6 , and PF6 complexes, respectively). PMID- 27555281 TI - Possible cures for clinical rabies: Are they already on the pharmacy shelf? PMID- 27555280 TI - Olfactomedin 1 negatively regulates NF-kappaB signalling and suppresses the growth and metastasis of colorectal cancer cells. AB - Uncontrolled growth and distant metastasis are hallmarks of colorectal cancer (CRC), but the mechanisms are poorly understood. Olfactomedin 1 (OLFM1), a member of the olfactomedin domain-containing protein family, plays an important role in the development of neurogenic tissues. Recently, OLFM1 deregulation was frequently observed in several cancers, and it was induced in colon cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine. However, the function of OLFM1 in CRC remains unknown. In this study, we reanalysed published microarray data and found that OLFM1 was significantly down-regulated in primary CRC samples compared to adjacent non-cancerous tissues. The results of immunohistochemistry indicated that decreased OLFM1 expression was significantly associated with lymph node status (p = 0.023), distant metastasis (p < 0.001), and AJCC/TNM stage (p = 0.013), and CRC patients with low OLFM1 expression had consistently poor overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Further analysis demonstrated that OLFM1 was epigenetically silenced in CRC tissues and cell lines via promoter hypermethylation. Overexpression and knockdown of OLFM1 attenuated and increased, respectively, CRC cells' proliferation, migration, and invasion in vitro and metastasis to the lung and liver in vivo. Mechanistically, the promotion of growth and metastasis of CRC cells by silencing of OLFM1 was associated with the activation of the non canonical NF-kappaB signalling pathway. OLFM1 interacted with NF-kappaB-inducing kinase (NIK; MAP3K14) and repressed the phosphorylation of its downstream substrate Ikappa B kinase alpha (IKKalpha). OLFM1 expression was negatively correlated with the phosphorylation level of IKKalpha in CRC tissue samples. Knockdown of NIK impaired the ability of OLFM1 to repress NF-kappaB signalling, cell growth or migration. Thus, OLFM1 may be a valuable biomarker and therapeutic target for CRC patients. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27555282 TI - A one-year effective reproduction number of the 2014-2015 Ebola outbreaks in the widespread West African countries and quantitative evaluation of air travel restriction measure. AB - BACKGROUND: The 2014-2015 Ebola outbreak in West Africa is the largest and longest Ebola Virus Disease (EVD) outbreak in the history, and the virus has escaped across countries and continents via air travel in this outbreak. METHOD: The interpolated data from WHO Ebola situation reports were used to estimate number of weekly infectious individuals and daily effective reproduction numbers (Rt) in Guinea, Liberia and Sierra Leone. A stochastic dynamic model was performed to estimate the risk of EVD importation into the top 20 final destination countries of air travelers departing from within the three epidemic countries, and the effectiveness of air travel restriction was subsequently evaluated. RESULTS: The daily Rt was estimated at 0.72-1.32 in Guinea, 0.62-1.38 in Liberia and 0.81-1.38 in Sierra Leone. The peak of EVD importation probability was observed in early November 2014 and the restriction of air travel may mitigate the risk up to 67.7% (95% CI 66.6-68.7). CONCLUSIONS: Our results suggest that restriction of air travels is effective in reducing the risk of EVD importation but controlling of the virus at the original affected countries is vitally more important for preventing inter-terrestrial dissemination of EVD. PMID- 27555283 TI - Historical review: Does falciparum malaria destroy isolated tribal populations? AB - Many isolated populations of tribal peoples were nearly destroyed when they first contacted infectious diseases particularly respiratory pathogens such as measles and smallpox. Surviving groups have often been found to have declining populations in the face of multiple social and infectious threats. Malaria, especially Plasmodium falciparum, was thought to be a major cause of depopulation in some tribal peoples isolated in tropical jungles. The dynamics of such host parasite interactions is unclear especially since most such populations would have had long histories of exposure to malaria. Three groups are individually reviewed: Meruts of Borneo, Yanomami of Amazonia, Jarawas of the Andaman Islands. The purpose of this review is to examine the role of falciparum malaria in the depopulation of some isolated tribal groups in order to understand what measures, if any, would be likely to prevent such losses. PMID- 27555284 TI - The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2 (JAK2) inhibitors versus JAK1 and JAK3. AB - Members of the Janus kinase (JAK) family are potential therapeutic targets. Abnormal signaling by mutant JAK2 is related to hematological malignancy, such as myeloproliferative neoplasms (MPNs), and tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). We discovered a potent and highly selective inhibitor of JAK2 over JAK1 and -3 based on the structure of 4 (2,5-triazole)-pyrrolopyrimidine. Among all triazole compounds tested, 2,5 triazole regioisomers more effectively inhibited JAK2 kinase activity than isomers with substitutions of various alkyl groups at the R2 position, except for methyl-substituted 1,5-triazole, which was more potent than the corresponding 1,4 and 2,5-triazoles. None of the synthesized 1,4-isomers inhibited all three JAK family members. Compounds with phenyl or tolyl group substituents at the R1 position were completely inactive compared with the corresponding analogues with a methyl substituted at the R1 position. As a result of this structure-activity relationship, 54, which is substituted with a cyclopropylmethyl moiety, exhibited significant inhibitory activity and selectivity (IC50=41.9nM, fold selectivity JAK1/2 10.6 and JAK3/2 58.1). Compound 54 also exhibited an equivalent inhibition of wild type JAK2 and the V617F mutant. Moreover, 54 inhibited the proliferation of HEL 92.1.7 cells, which carry JAK2 V617F, and gefitinib-resistant HCC827 cells. Compound 54 also suppressed STAT3 phosphorylation at Y705. PMID- 27555285 TI - Intrinsically disordered regions stabilize the helical form of the C-terminal domain of RfaH: A molecular dynamics study. AB - RfaH protein functions as both transcription anti-terminator and translation enhancer in bacteria. Recent studies have shown that the C-terminal domain (CTD) is an alpha-helical hairpin (two-helix bundle) in full-length RfaH, despite the intrinsically favored beta-barrel structure. Here, we carried out MUs-timescale molecular dynamics (MD) simulations for the wild-type (WT) RfaH, its E48S mutant and an established model without the intrinsically disordered region (IDR1) linking the CTD and the N-terminal domain (NTD). Our simulations showed that the WT can be well stabilized by our RSFF1 force field, while the E48S mutant and the model without IDR1 undergo considerable structural change, which is in good agreement with experimental observations. The IDR1 plays important roles in stabilizing the hydrophobic environment near the crucial E48-R138 salt-bridge as well as in tethering alpha4 helix in CTD to alpha3 helix in NTD. In the absence of the IDR1, destabilization of key interdomain contacts and unfolding of the CTD alpha5 helix were observed in the simulation. In addition, the intrinsically disordered tail of the CTD (IDR2) is also of great significance to stabilize the bound conformation of CTD. These findings provide important implications for consideration of simulations in revealing the functions of residues invisible in a crystal structure. PMID- 27555286 TI - New antiproliferative 7-(4-(N-substituted carbamoylmethyl)piperazin-1-yl) derivatives of ciprofloxacin induce cell cycle arrest at G2/M phase. AB - New N-4-piperazinyl derivatives of ciprofloxacin 2a-g were prepared and tested for their cytotoxic activity. The primary in vitro one dose anticancer assay experienced promising cytotoxic activity against different cancer cell lines especially non-small cell lung cancer. Independently, compounds 2b, 2d, 2f and 2g showed anticancer activity against human non-small cell lung cancer A549 cells (IC50=14.8, 24.8, 23.6 and 20.7MUM, respectively) compared to the parent ciprofloxacin (IC50 >100MUM) and doxorubicin as a positive control (IC50=1MUM). The flow cytometric analysis for 2b showed dose dependent G2/M arrest in A549 cells. Also, 2b increased the expression of p53 and p21 and decreased the expression of cyclin B1 and Cdc2 proteins in A549 cells without any effect on the same proteins expression in WI-38 cells. Specific inhibition of p53 by pifithrin alpha reversed the G2/M phase arrest induced by the 2b compound, suggesting contribution of p53 to increase. Taken together, 2b induced G2/M phase arrest via p53/p21 dependent pathway. The results indicate that 2b can be used as a lead compound for further development of new derivatives against non-small cell lung cancer. PMID- 27555287 TI - Exploring the cell signalling in hepatocyte differentiation. AB - The liver is the second largest organ in the human body and is responsible for several functions that directly contribute to homeostasis. Hepatocytes are the main parenchymal liver cells that regulate multiple biochemical and metabolic functions and the synthesis of substances important to the body. Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesoderm, which can be obtained from various tissues. Under certain conditions, MSCs can differentiate into several cell types, including hepatocytes. Post-transcriptional regulations of liver development signalling and hepatocyte differentiation have been demonstrated. At the post-transcriptional level, microRNAs have emerged as precursors for determining cell fate during differentiation. MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of gene expression. They can determine the stem cell fate by repressing the translation of target mRNAs. In this review, we outline signalling pathways involved in stem cell differentiation to hepatocytes and its interplay with liver development. Hepatic differentiation models in two-dimensional and three-dimensional cultures used to analyse signalling mechanisms will be described. We also highlight the possible miRNAs involved in this process and the transdifferentiation signalling mechanisms present in hepatocytes. PMID- 27555289 TI - Hyperuricemia is associated with increased hospitalization risk and healthcare costs: Evidence from an administrative database in Italy. AB - BACKGROUND AND AIM: Chronic hyperuricemia is responsible for a relevant burden of articular diseases and cardio-nephrometabolic disorders. We evaluated the effect of high serum uric acid (SUA) levels on hospitalization risk and mortality and on healthcare costs in a real-life setting. METHODS AND RESULTS: We conducted a retrospective analysis using a large administrative database and a clinical registry among 112,170 subjects from three Italian local health units. Individuals were divided into four groups according to their SUA levels: <6 mg/dL (66.5%), >6 mg/dL and <=7 mg/dL (19.3%), >7 mg/dL and <=8 mg/dL (8.7%), and >8 mg/dL (5.5%). Compared to those with SUA level of <6 mg/dL, the risk of hospitalization related to gout and/or nephrolithiasis was higher in the three groups of patients with higher SUA levels (1.51, P = 0.100; 2.21, P = 0.005; and 1.17, P = 0.703, respectively). A similar trend was also observed for hospitalization due to chronic kidney disease (CKD) (1.31, P < 0.001; 1.40, P < 0.001; and 2.18, P < 0.001, respectively) and cardiovascular disease (CVD) (1.08, P < 0.001; 1.23, P < 0.001; and 1.67, P < 0.001, respectively) and for all-cause mortality (0.97, P = 0.309; 1.21, P < 0.001; and 2.15, P < 0.001). The mean annual healthcare costs were higher in patients with higher SUA level (?2752, ?2957, ?3386, and ?4607, respectively) mainly because of a progressive increase in hospitalization costs per patient (from ? 1515 for SUA <6 mg/dL to ? 3096 for SUA >8 mg/dL). CONCLUSIONS: Increased SUA levels are associated with an increased risk of hospitalizations related to hyperuricemia, CKD, and CVDs and total mortality, and consequently with higher total healthcare costs and hospitalization costs per patient. PMID- 27555288 TI - Palmitate-induced Endoplasmic Reticulum stress and subsequent C/EBPalpha Homologous Protein activation attenuates leptin and Insulin-like growth factor 1 expression in the brain. AB - The peptide hormones Insulin-like growth factor-1 (IGF1) and leptin mediate a myriad of biological effects - both in the peripheral and central nervous systems. The transcription of these two hormones is regulated by the transcription factor C/EBPalpha, which in turn is negatively regulated by the transcription factor C/EBP Homologous Protein (CHOP), a specific marker of endoplasmic reticulum (ER) stress. In the peripheral system, disturbances in leptin and IGF-1 levels are implicated in a variety of metabolic diseases including obesity, diabetes, atherosclerosis and cardiovascular diseases. Current research suggests a positive correlation between consumption of diets rich in saturated free fatty acids (sFFA) and metabolic diseases. Induction of ER stress and subsequent dysregulation in the expression levels of leptin and IGF-1 have been shown to mediate sFFA-induced metabolic diseases in the peripheral system. Palmitic acid (palmitate), the most commonly consumed sFFA, has been shown to be up-taken by the brain, where it may promote neurodegeneration. However, the extent to which palmitate induces ER stress in the brain and attenuates leptin and IGF1 expression has not been determined. We fed C57BL/6J mice a palmitate enriched diet and determined effects on the expression levels of leptin and IGF1 in the hippocampus and cortex. We further determined the extent to which ER stress and subsequent CHOP activation mediate the palmitate effects on the transcription of leptin and IGF1. We demonstrate that palmitate induces ER stress and decreases leptin and IGF1 expression by inducing the expression of CHOP. The molecular chaperone 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress, precludes the palmitate-evoked down-regulation of leptin and IGF1 expression. Furthermore, the activation of CHOP in response to ER stress is pivotal in the attenuation of leptin and IGF1 expression as knocking-down CHOP in mice or in SH SY5Y and Neuro-2a (N2a) cells rescues the palmitate-induced mitigation in leptin and IGF1 expression. Our study implicates for the first time ER stress-induced CHOP activation in the brain as a mechanistic link in the palmitate-induced negative regulation of leptin and IGF1, two neurotrophic cytokines that play an indispensable role in the mammalian brain. PMID- 27555290 TI - Spontaneous eye blink rate as predictor of dopamine-related cognitive function-A review. AB - An extensive body of research suggests the spontaneous eye blink rate (EBR) is a non-invasive indirect marker of central dopamine (DA) function, with higher EBR predicting higher DA function. In the present review we provide a comprehensive overview of this literature. We broadly divide the available research in studies that aim to disentangle the dopaminergic underpinnings of EBR, investigate its utility in diagnosis of DA-related disorders and responsivity to drug treatment, and, lastly, investigate EBR as predictor of individual differences in DA-related cognitive performance. We conclude (i) EBR can reflect both DA receptor subtype D1 and D2 activity, although baseline EBR might be most strongly related to the latter, (ii) EBR can predict hypo- and hyperdopaminergic activity as well as normalization of this activity following treatment, and (iii) EBR can reliably predict individual differences in performance on many cognitive tasks, in particular those related to reward-driven behavior and cognitive flexibility. In sum, this review establishes EBR as a useful predictor of DA in a wide variety of contexts. PMID- 27555293 TI - The Luminescence of CH3 NH3 PbBr3 Perovskite Nanoparticles Crests the Summit and Their Photostability under Wet Conditions is Enhanced. AB - CH3 NH3 PbBr3 perovskite nanoparticles (PAD ) are prepared with a photoluminescence quantum yield of ~100% in air atmosphere by using the quasi spherical shaped 2-adamantylammonium bromide (ADBr) as the only capping ligand. The photostability under wet conditions of this kind of nanoparticles is enhanced by using cucurbit[7]uril-adamantylammonium (AD@CB) host-guest complexes as the capping ligand. PMID- 27555291 TI - A molecular conundrum involving hypothalamic responses to and roles of long non coding RNAs following food deprivation. AB - Long non-coding RNAs (lncRNAs) are one of most poorly understood RNA classes in the mammalian transcriptome. However, they are emerging as important players in transcriptional regulation, especially within the complexity of the nervous system. This review summarizes the known information about lncRNAs, and their roles in endocrine processes, as well as the lesser-known information about lncRNAs in the brain, and in the neuroendocrine hypothalamus. A "call-to-action" is presented for researchers to use archival transcriptome data to characterize differentially expressed lncRNA species within the hypothalamus. In accordance, we analyze for differential-expression of lncRNA between normal mice and mice with a targeted deletion of the nescient helix-loop-helix 2 gene, and between C57Bl/6 and 129Sv/J mice. Finally, strategies and approaches for researchers to analyze their own datasets or those on the NCBI GEO datasets repository are provided, in hopes that future studies will reveal many new roles for lncRNAs in hypothalamic physiological responses, solving this so-called "molecular conundrum" once and for all. PMID- 27555294 TI - Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia. AB - BACKGROUND: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. METHOD: Children (1.0 17.9 years) diagnosed with ALL, treated with asparaginase for 30 weeks, according to the NOPHO ALL2008 protocol at the University Hospital Rigshospitalet, Copenhagen, Denmark, were eligible. Pancreatic enzymes, triglycerides, and cholesterol were measured regularly. RESULTS: Thirty-one patients were included. Seven patients were diagnosed with AAP. HTG was most evident when PEG asparaginase and dexamethasone were administered concomitantly. Overall, there was no significant difference in triglyceride levels in patients who experienced AAP and patients who did not. An increase in triglyceride levels during concomitant dexamethasone therapy in delayed intensification was significantly associated with an increase in pancreas-specific amylase levels two weeks later (P = 0.005). CONCLUSIONS: AAP does not seem to be associated with HTG. Continuous monitoring of pancreas enzymes does not predict AAP. PMID- 27555295 TI - MiR-29a promotes cell proliferation and EMT in breast cancer by targeting ten eleven translocation 1. AB - Increasing evidence has shown that microRNAs played an important role in regulating carcinogenesis. However, the role of miR-29a in breast cancer is still unclear. Herein, we showed that miR-29a was significantly up-regulated in breast cancer as compared with non-tumor tissues. Moreover, the up-regulation of miR-29a was significantly correlated with tumor metastasis and shorter overall survival in breast cancer patients. Knockdown of miR-29a in breast cancer cell lines inhibited cell proliferation and migration. Furthermore, data from bioinformatic analysis validated by dual-luciferase reporter gene assay showed that ten eleven translocation 1 (TET1) was a direct target of miR-29a, and over-expression of TET1 inhibited cell proliferation and migration which could be induced by the up regulation of miR-29a. TET1 silencing promoted cell growth and migration in breast cancer. MiR-29a over-expression had the same effect. MiR-29a targets TET1, down regulates its expression and thus promotes EMT in breast cancer. Altogether, we demonstrate that miR-29a acts as a tumor activator by targeting TET1 and induces cell proliferation and EMT in breast cancer. PMID- 27555296 TI - In utero exposure to gestational diabetes mellitus conditions TLR4 and TLR2 activated IL-1beta responses in spleen cells from rat offspring. AB - Fetal exposure to gestational diabetes mellitus (GDM) is associated with a higher risk of youth-onset insulin resistance and type 2 diabetes. We have previously shown that the rat offspring of GDM dams are insulin resistant when compared to the offspring of lean dams. Since inflammation influences insulin sensitivity, we examined the impact of fetal exposure to GDM on inflammatory responses in the offspring. In rats, we compared inflammatory activity in newborn pups as well as 16week-old young-adult offspring from lean control dams with offspring from high fat and sucrose diet (HFS)-induced GDM dams. To determine whether there are additive effects of exposure to GDM and post-weaning diets, offspring of lean and GDM dams were fed either low fat or HFS diets until 16weeks of age. Plasma levels of interleukin(IL)-1beta were elevated in the offspring of GDM dams. To determine whether this was related to immune reactivity, spleen cells from both the newborn and 16week-old offspring were isolated and reactivity to the toll-like receptor activators, pam3CSK4 and lipopolysaccharides were measured over a 72h timeframe. Spleen cells of GDM dams exhibited sustained stimulation of interleukin(IL)-1beta and IL-10 production, whereas IL-1beta and IL-10 synthesis diminished over time in spleen cells from the offspring of lean dams. Additive effects of GDM exposure and post-weaning HFS diet were not observed, suggesting the effects of GDM on cytokine production are independent of the post-weaning diet. Thus, we conclude that exposure to GDM in utero may condition the immune reactivity of spleen cells. PMID- 27555292 TI - Transgenerational cardiology: One way to a baby's heart is through the mother. AB - Despite decades of progress, congenital heart disease remains a major cause of mortality and suffering in children and young adults. Prevention would be ideal, but formidable biological and technical hurdles face any intervention that seeks to target the main causes, genetic mutations in the embryo. Other factors, however, significantly modify the total risk in individuals who carry mutations. Investigation of these factors could lead to an alternative approach to prevention. To define the risk modifiers, our group has taken an "experimental epidemiologic" approach via inbred mouse strain crosses. The original intent was to map genes that modify an individual's risk of heart defects caused by an Nkx2 5 mutation. During the analysis of >2000 Nkx2-5(+/-) offspring from one cross we serendipitously discovered a maternal-age associated risk, which also exists in humans. Reciprocal ovarian transplants between young and old mothers indicate that the incidence of heart defects correlates with the age of the mother and not the oocyte, which implicates a maternal pathway as the basis of the risk. The quantitative risk varies between strain backgrounds, so maternal genetic polymorphisms determine the activity of a factor or factors in the pathway. Most strikingly, voluntary exercise by the mother mitigates the risk. Therefore, congenital heart disease can in principle be prevented by targeting a maternal pathway even if the embryo carries a causative mutation. Further mechanistic insight is necessary to develop an intervention that could be implemented on a broad scale, but the physiology of maternal-fetal interactions, aging, and exercise are notoriously complex and undefined. This suggests that an unbiased genetic approach would most efficiently lead to the relevant pathway. A genetic foundation would lay the groundwork for human studies and clinical trials. PMID- 27555297 TI - Direct effect of glucocorticoids on glucose-activated adult rat beta-cells increases their cell number and their functional mass for transplantation. AB - Compounds that increase beta-cell number can serve as beta-cell replacement therapies in diabetes. In vitro studies have identified several agents that can activate DNA synthesis in primary beta-cells but only in small percentages of cells and without demonstration of increases in cell number. We used whole well multiparameter imaging to first screen a library of 1,280 compounds for their ability to recruit adult rat beta-cells into DNA synthesis and then assessed influences of stimulatory agents on the number of living cells. The four compounds with highest beta-cell recruitment were glucocorticoid (GC) receptor ligands. The GC effect occurred in glucose-activated beta-cells and was associated with increased glucose utilization and oxidation. Hydrocortisone and methylprednisolone almost doubled the number of beta-cells in 2 wk. The expanded cell population provided an increased functional beta-cell mass for transplantation in diabetic animals. These effects are age dependent; they did not occur in neonatal rat beta-cells, where GC exposure suppressed basal replication and was cytotoxic. We concluded that GCs can induce the replication of adult rat beta-cells through a direct action, with intercellular differences in responsiveness that have been related to differences in glucose activation and in age. These influences can explain variability in GC-induced activation of DNA synthesis in rat and human beta-cells. Our study also demonstrated that beta cells can be expanded in vitro to increase the size of metabolically adequate grafts. PMID- 27555299 TI - Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review. AB - The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesized and reported as providing sufficient or insufficient "evidence of age related muscle anabolic resistance". Subsequently, three models were established to compare age-related differences in the MPS response to 1) exercise alone, 2) amino acid-based nutrition alone, or 3) the combination of exercise and amino acid-based nutrition. Following exercise alone, 8 of the 17 study arms provided sufficient evidence of age-related muscle anabolic resistance, while in response to amino acid-based nutrition alone, 8 of the 21 study arms provided sufficient evidence of age-related muscle anabolic resistance. When exercise and amino acid based nutrition were combined, only 2 of the 10 study arms provided sufficient evidence of age-related muscle anabolic resistance. Our results highlight that optimization of exercise and amino acid-based nutrition is sufficient to induce a comparable MPS response between young and older individuals. However, the exercise volume completed and/or the amino acid/protein dose and leucine content must exceed a certain threshold to stimulate equivalent MPS rates in young and older adults, below which age-related muscle anabolic resistance may become apparent. PMID- 27555300 TI - Occupational contact dermatitis caused by 1,3-benzenedimethanamine, N-(2 phenylethyl) derivatives in hardeners for epoxy paints and coatings. AB - BACKGROUND: Amines in epoxy hardeners are significant causes of occupational allergic contact dermatitis among workers who use epoxy resin systems. OBJECTIVES: To describe a novel group of contact allergens: N-(2-phenylethyl) derivatives of the reactive amine 1,3-benzenedimethanamine (1,3-BDMA). METHODS: We describe the clinical examinations and exposure of 6 patients with occupational contact allergy to derivatives of 1,3-BDMA. RESULTS: Of the 6 patients, 4 were spray painters who used epoxy paints, 1 was a floor layer who handled a variety of epoxy coatings, and 1 was a worker in epoxy hardener manufacture. We were able to confirm exposure to epoxy hardeners that contained derivatives of 1,3-BDMA in 5 of the 6 sensitized patients. Despite the close structural resemblance between derivatives of 1,3-BDMA and m-xylylenediamine (MXDA), only 3 patients reacted positively to MXDA. Concomitant contact allergy to diglycidyl ether of bisphenol A resin was seen in 2 of the 6 patients. CONCLUSIONS: Because of the lack of a commercially available patch test substance, the diagnosis of contact allergy to derivatives of 1,3-BDMA requires patch testing with either the epoxy hardener product or a hardener ingredient that contains the derivatives of 1,3-BDMA. PMID- 27555298 TI - Loss of CTRP1 disrupts glucose and lipid homeostasis. AB - C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q family with notable metabolic and cardiovascular functions. We have previously shown that CTRP1 infusion lowers blood glucose and that transgenic mice with elevated circulating CTRP1 are protected from diet-induced obesity and insulin resistance. Here, we used a genetic loss-of-function mouse model to address the requirement of CTRP1 for metabolic homeostasis. Despite similar body weight, food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet developed insulin resistance and hepatic steatosis. Impaired glucose metabolism in Ctrp1 KO mice was associated with increased hepatic gluconeogenic gene expression and decreased skeletal muscle glucose transporter glucose transporter 4 levels and AMP activated protein kinase activation. Loss of CTRP1 enhanced the clearance of orally administered lipids but did not affect intestinal lipid absorption, hepatic VLDL-triglyceride export, or lipoprotein lipase activity. In contrast to triglycerides, hepatic cholesterol levels were reduced in Ctrp1 KO mice, paralleling the reduced expression of cholesterol synthesis genes. Contrary to expectations, when challenged with a high-fat diet to induce obesity, Ctrp1 KO mice had increased physical activity and reduced body weight, adiposity, and expression of lipid synthesis and fibrotic genes in adipose tissue; these phenotypes were linked to elevated FGF-21 levels. Due in part to increased hepatic AMP-activated protein kinase activation and reduced expression of lipid synthesis genes, Ctrp1 KO mice fed a high-fat diet also had reduced liver and serum triglyceride and cholesterol levels. Taken together, these results provide genetic evidence to establish the significance of CTRP1 to systemic energy metabolism in different metabolic and dietary contexts. PMID- 27555301 TI - Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen. AB - BACKGROUND: Prevalence and risks for elevated liver enzymes have not been studied systematically in children with CF identified by newborn screen. METHODS: 298 CF children identified by newborn screen since 1982. AST, ALT and GGT tested at annual visits. Percent of children with 1 or >=2 values of elevated AST, ALT and GGT determined. Relationship of liver enzymes to clinical factors or subsequent liver disease was analyzed RESULTS: At least one abnormal value for AST (63%), ALT (93%) and ALT >=1.5* ULN (52%) occurred by 21years of age. Liver enzyme elevations were not correlated with CFTR mutation, meconium ileus or ethnicity. AST and GGT >=1.5* ULN were associated with later advanced liver disease HR (CI) 6.53 (2.02-21.1) and 4.03 (1.15-13.45), respectively. CONCLUSIONS: Elevated liver enzymes are common during childhood in CF patients identified by newborn screen. Elevated AST and GGT may be markers for risk of advanced liver disease. PMID- 27555302 TI - Intrahepatic NK cells function suppressed in advanced liver fibrosis. AB - BACKGROUND: Although numerous epidemiological studies indicate that hepatitis B virus-related liver fibrosis (HBV-LF), particularly cirrhosis, represents the main risk factor for liver cancer development, the mechanisms determining the persistence of fibrosis and liver cancer pathogenesis are still poorly defined. Few studies have investigated the status of NK cells during different stages of HBV-LF. METHODS: Liver tissues at least 3 cm away from the tumour site and peripheral blood were obtained simultaneously from 32 HBV-infected patients undergoing surgery for HCC at the medical centre of Sun Yat-sen University. We detected the amount of NK cells and analysed the phenotype and function of NK cells by flow cytometry. RESULTS: We found that there was no difference in the amount of circulating and intrahepatic NK cells between early and advanced HBV LF. However, NKp46 expression on intrahepatic NK cells decreased and productions of IFN-gamma and perforin of intrahepatic NK cells declined apparently in patients with advanced HBV-LF. CONCLUSION: In the present study, we displayed that in patients with advanced HBV-LF, the expression of NKp46 on intrahepatic NK cells as well as productions of IFN-gamma and perforin of intrahepatic NK cells decreased significantly. These results indicated that the immune function of intrahepatic NK cells in patients with advanced HBV-LF was suppressed distinctly, which provided new insight into the potential role of NK cells in the persistence of fibrosis and into the occurrence of HCC following cirrhosis. PMID- 27555303 TI - Rare complications of acute otitis media in a 2-year-old child. PMID- 27555304 TI - What's in a Name? Species-Wide Whole-Genome Sequencing Resolves Invasive and Noninvasive Lineages of Salmonella enterica Serotype Paratyphi B. AB - For 100 years, it has been obvious that Salmonella enterica strains sharing the serotype with the formula 1,4,[5],12:b:1,2-now known as Paratyphi B-can cause diseases ranging from serious systemic infections to self-limiting gastroenteritis. Despite considerable predicted diversity between strains carrying the common Paratyphi B serotype, there remain few methods that subdivide the group into groups that are congruent with their disease phenotypes. Paratyphi B therefore represents one of the canonical examples in Salmonella where serotyping combined with classical microbiological tests fails to provide clinically informative information. Here, we use genomics to provide the first high-resolution view of this serotype, placing it into a wider genomic context of the Salmonella enterica species. These analyses reveal why it has been impossible to subdivide this serotype based upon phenotypic and limited molecular approaches. By examining the genomic data in detail, we are able to identify common features that correlate with strains of clinical importance. The results presented here provide new diagnostic targets, as well as posing important new questions about the basis for the invasive disease phenotype observed in a subset of strains. IMPORTANCE: Salmonella enterica strains carrying the serotype Paratyphi B have long been known to possess Jekyll and Hyde characteristics; some cause gastroenteritis, while others cause serious invasive disease. Understanding what makes up the population of strains carrying this serotype, as well as the source of their invasive disease, is a 100-year-old puzzle that we address here using genomics. Our analysis provides the first high-resolution view of this serotype, placing strains carrying serotype Paratyphi B into the wider genomic context of the Salmonella enterica species. This work reveals a history of disease dating back to the middle ages, caused by a group of distinct lineages with various abilities to cause invasive disease. By quantifying the key genomic differences between the invasive and noninvasive populations, we are able to identify key virulence-related targets that can form the basis of simple, rapid, point-of-care tests. PMID- 27555306 TI - Mechanisms by Which Interleukin-12 Corrects Defective NK Cell Anticryptococcal Activity in HIV-Infected Patients. AB - Cryptococcus neoformans is a pathogenic yeast and a leading cause of life threatening meningitis in AIDS patients. Natural killer (NK) cells are important immune effector cells that directly recognize and kill C. neoformans via a perforin-dependent cytotoxic mechanism. We previously showed that NK cells from HIV-infected patients have aberrant anticryptococcal killing and that interleukin 12 (IL-12) restores the activity at least partially through restoration of NKp30. However, the mechanisms causing this defect or how IL-12 restores the function was unknown. By examining the sequential steps in NK cell killing of Cryptococcus, we found that NK cells from HIV-infected patients had defective binding of NK cells to C. neoformans Moreover, those NK cells that bound to C. neoformans failed to polarize perforin-containing granules to the microbial synapse compared to healthy controls, suggesting that binding was insufficient to restore a defect in perforin polarization. We also identified lower expression of intracellular perforin and defective perforin release from NK cells of HIV infected patients in response to C. neoformans Importantly, treatment of NK cells from HIV-infected patients with IL-12 reversed the multiple defects in binding, granule polarization, perforin content, and perforin release and restored anticryptococcal activity. Thus, there are multiple defects in the cytolytic machinery of NK cells from HIV-infected patients, which cumulatively result in defective NK cell anticryptococcal activity, and each of these defects can be reversed with IL-12. IMPORTANCE: The mechanisms by which NK cells bind directly to pathogens and deploy their deadly cytolytic machinery during microbial host defense are only beginning to be elucidated. With the goal of understanding this process, we used NK cells from HIV-infected patients, which were known to have a defect in killing of Cryptococcus neoformans Taking advantage of previous studies that had shown that IL-12 restored killing, we used the cytokine as a gain-of function approach to define the relevance of multiple steps in the recognition and cytolytic pathway. We demonstrated that NK cells from HIV-infected patients failed to kill Cryptococcus due to defects in perforin expression, granule polarization, and release of perforin. Additionally, IL-12 restored recognition of C. neoformans through binding of the NK-activating receptor NKp30. These observations identify important mechanisms used by NK cells to kill microbes and determine that defects in NK cells from HIV-infected patients are reversible. PMID- 27555305 TI - The Core and Seasonal Microbiota of Raw Bovine Milk in Tanker Trucks and the Impact of Transfer to a Milk Processing Facility. AB - Currently, the bacterial composition of raw milk in tanker trucks and the outcomes of transfer and storage of that milk at commercial processing facilities are not well understood. We set out to identify the bacteria in raw milk collected for large-scale dairy product manufacturing. Raw bovine milk samples from 899 tanker trucks arriving at two dairy processors in San Joaquin Valley of California during three seasons (spring, summer, and fall) were analyzed by community 16S rRNA gene sequencing. This analysis revealed highly diverse bacterial populations, which exhibited seasonal differences. Raw milk collected in the spring contained the most diverse bacterial communities, with the highest total cell numbers and highest proportions being those of Actinobacteria Even with this complexity, a core microbiota was present, consisting of 29 taxonomic groups and high proportions of Streptococcus and Staphylococcus and unidentified members of Clostridiales Milk samples were also collected from five large-volume silos and from 13 to 25 tankers whose contents were unloaded into each of them during 2 days in the summer. Transfer of the milk to storage silos resulted in two community types. One group of silos contained a high proportion of Streptococcus spp. and was similar in that respect to the tankers that filled them. The community found in the other group of silos was distinct and dominated by Acinetobacter Overall, despite highly diverse tanker milk community structures, distinct milk bacterial communities were selected within the processing facility environment. This knowledge can inform the development of new sanitation procedures and process controls to ensure the consistent production of safe and high-quality dairy products on a global scale. IMPORTANCE: Raw milk harbors diverse bacteria that are crucial determinants of the quality and safety of fluid milk and (fermented) dairy products. These bacteria enter farm milk during transport, storage, and processing. Although pathogens are destroyed by pasteurization, not all bacteria and their associated enzymes are eliminated. Our comprehensive analyses of the bacterial composition of raw milk upon arrival and shortly after storage at major dairy processors showed that the communities of milk microbiota are highly diverse. Even with these differences, there was a core microbiota that exhibited distinct seasonal trends. Remarkably, the effects of the processing facility outweighed those of the raw milk microbiome and the microbial composition changed distinctly within some but not all silos within a short time after transfer. This knowledge can be used to inform cleaning and sanitation procedures as well as to enable predictions of the microbial communities in raw milk that result in either high-quality or defective products. PMID- 27555307 TI - Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion. AB - Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia's sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-Rac(CA)) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-Rac(CA)-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. IMPORTANCE: The encystation process is crucial for the transmission of giardiasis and the life cycle of many protists. Encystation for Giardia lamblia involves the assembly of a protective cyst wall via sequential production, trafficking, and secretion of cyst wall material. However, the regulatory pathways that coordinate cargo maturation and secretion remain unknown. Here, we asked whether the signaling activities of G. lamblia's single Rho family GTPase, GlRac, might have a regulatory role in the encystation process. We show that GlRac localizes to endomembranes and its signaling activities regulate the production of cyst wall protein 1 (CWP1), the maturation of encystation-specific vesicles (ESVs), and secretion of CWP1. We also show that secreted CWP1 is available for the development of cysts at the population level, a finding that in part could explain why Giardia encystation proceeds more efficiently at high cell densities. PMID- 27555308 TI - Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome. AB - Two recent studies have reanalyzed previously published data and found that when data sets were analyzed independently, there was limited support for the widely accepted hypothesis that changes in the microbiome are associated with obesity. This hypothesis was reconsidered by increasing the number of data sets and pooling the results across the individual data sets. The preferred reporting items for systematic reviews and meta-analyses guidelines were used to identify 10 studies for an updated and more synthetic analysis. Alpha diversity metrics and the relative risk of obesity based on those metrics were used to identify a limited number of significant associations with obesity; however, when the results of the studies were pooled by using a random-effect model, significant associations were observed among Shannon diversity, the number of observed operational taxonomic units, Shannon evenness, and obesity status. They were not observed for the ratio of Bacteroidetes and Firmicutes or their individual relative abundances. Although these tests yielded small P values, the difference between the Shannon diversity indices of nonobese and obese individuals was 2.07%. A power analysis demonstrated that only one of the studies had sufficient power to detect a 5% difference in diversity. When random forest machine learning models were trained on one data set and then tested by using the other nine data sets, the median accuracy varied between 33.01 and 64.77% (median, 56.68%). Although there was support for a relationship between the microbial communities found in human feces and obesity status, this association was relatively weak and its detection is confounded by large interpersonal variation and insufficient sample sizes. IMPORTANCE: As interest in the human microbiome grows, there is an increasing number of studies that can be used to test numerous hypotheses across human populations. The hypothesis that variation in the gut microbiota can explain or be used to predict obesity status has received considerable attention and is frequently mentioned as an example of the role of the microbiome in human health. Here we assessed this hypothesis by using 10 independent studies and found that although there is an association, it is smaller than can be detected by most microbiome studies. Furthermore, we directly tested the ability to predict obesity status on the basis of the composition of an individual's microbiome and found that the median classification accuracy is between 33.01 and 64.77%. This type of analysis can be used to design future studies and expanded to explore other hypotheses. PMID- 27555309 TI - Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo. AB - We recently showed that human gut Bacteroidales species secrete antimicrobial proteins (BSAPs), and we characterized in vitro the first such BSAP produced by Bacteroides fragilis In this study, we identified a second potent BSAP produced by the ubiquitous and abundant human gut species Bacteroides uniformis The two BSAPs contain a membrane attack complex/perforin (MACPF) domain but share very little sequence similarity. We identified the target molecules of BSAP-sensitive cells and showed that each BSAP targets a different class of surface molecule: BSAP-1 targets an outer membrane protein of sensitive B. fragilis strains, and BSAP-2 targets the O-antigen glycan of lipopolysaccharide (LPS) of sensitive B. uniformis strains. Species-wide genomic and phenotypic analyses of B. fragilis and B. uniformis showed that BSAP-producing strains circumvent killing by synthesizing an orthologous nontargeted surface molecule. The BSAP genes are adjacent to the gene(s) encoding their target replacements, suggesting coacquisition. Using a gnotobiotic mouse competitive-colonization model, we found that the BSAP surface targets are important for colonization of the mammalian gut, thereby explaining why they are maintained in sensitive strains and why they were replaced rather than deleted in BSAP-producing strains. Using isogenic BSAP producing, -sensitive, and -resistant strains, we show that a BSAP-producing strain outcompetes a sensitive strain but not a resistant strain in the mammalian gut. Human gut metagenomic datasets reveal that BSAP-1-sensitive strains do not cooccur with BSAP-1-producing strains in human gut microbiotas, further supporting the idea that BSAPs are important competitive factors with relevance to the strain-level composition of the human gut microbiota. IMPORTANCE: We know relatively little about the ecology of the human intestinal microbiota and the combination of factors that dictate which strains and species occupy an individual's gut microbial community. Interference competition, mediated by bacterial factors that directly harm other members, is beginning to be appreciated as important in contributing to species- and strain-level dynamics of abundant gut bacteria. Here, we show that gut Bacteroidales secrete antimicrobial proteins (BSAPs) that antagonize strains of the same species. We show that BSAPs target molecules of sensitive cells that are important for gut colonization and therefore are maintained in sensitive cells. In an experimental animal model of gut colonization, a BSAP-1-producing strain antagonized and outcompeted an isogenic sensitive strain. Furthermore, metagenomic analyses showed that BSAP-1 producing and -sensitive strains are not found together in human gut microbiotas. These data suggest that BSAPs are strong ecological drivers shaping the strain level composition of gut communities. PMID- 27555310 TI - Comparative Community Proteomics Demonstrates the Unexpected Importance of Actinobacterial Glycoside Hydrolase Family 12 Protein for Crystalline Cellulose Hydrolysis. AB - Glycoside hydrolases (GHs) are key enzymes in the depolymerization of plant derived cellulose, a process central to the global carbon cycle and the conversion of plant biomass to fuels and chemicals. A limited number of GH families hydrolyze crystalline cellulose, often by a processive mechanism along the cellulose chain. During cultivation of thermophilic cellulolytic microbial communities, substantial differences were observed in the crystalline cellulose saccharification activities of supernatants recovered from divergent lineages. Comparative community proteomics identified a set of cellulases from a population closely related to actinobacterium Thermobispora bispora that were highly abundant in the most active consortium. Among the cellulases from T. bispora, the abundance of a GH family 12 (GH12) protein correlated most closely with the changes in crystalline cellulose hydrolysis activity. This result was surprising since GH12 proteins have been predominantly characterized as enzymes active on soluble polysaccharide substrates. Heterologous expression and biochemical characterization of the suite of T. bispora hydrolytic cellulases confirmed that the GH12 protein possessed the highest activity on multiple crystalline cellulose substrates and demonstrated that it hydrolyzes cellulose chains by a predominantly random mechanism. This work suggests that the role of GH12 proteins in crystalline cellulose hydrolysis by cellulolytic microbes should be reconsidered. IMPORTANCE: Cellulose is the most abundant organic polymer on earth, and its enzymatic hydrolysis is a key reaction in the global carbon cycle and the conversion of plant biomass to biofuels. The glycoside hydrolases that depolymerize crystalline cellulose have been primarily characterized from isolates. In this study, we demonstrate that adapting microbial consortia from compost to grow on crystalline cellulose generated communities whose soluble enzymes exhibit differential abilities to hydrolyze crystalline cellulose. Comparative proteomics of these communities identified a protein of glycoside hydrolase family 12 (GH12), a family of proteins previously observed to primarily hydrolyze soluble substrates, as a candidate that accounted for some of the differences in hydrolytic activities. Heterologous expression confirmed that the GH12 protein identified by proteomics was active on crystalline cellulose and hydrolyzed cellulose by a random mechanism, in contrast to most cellulases that act on the crystalline polymer in a processive mechanism. PMID- 27555311 TI - A Full-Length Infectious cDNA Clone of Zika Virus from the 2015 Epidemic in Brazil as a Genetic Platform for Studies of Virus-Host Interactions and Vaccine Development. AB - An arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barre syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a reverse genetic system based on an epidemic ZIKV strain. Here, we describe the generation and characterization in cell cultures of an infectious cDNA clone of ZIKV isolated from the 2015 epidemic in Brazil. The cDNA-derived ZIKV replicated efficiently in a variety of cell lines, including those of both neuronal and placental origin. We observed that the growth of cDNA-derived virus was attenuated compared to the growth of the parental isolate in most cell lines, which correlates with substantial differences in sequence heterogeneity between these viruses that were determined by deep-sequencing analysis. Our findings support the role of genetic diversity in maintaining the replicative fitness of viral populations under changing conditions. Moreover, these results indicate that caution should be exercised when interpreting the results of reverse-genetics experiments in attempts to accurately predict the biology of natural viruses. Finally, a Vero cell-adapted cDNA clone of ZIKV was generated that can be used as a convenient platform for studies aimed at the development of ZIKV vaccines and therapeutics. IMPORTANCE: The availability of genetic tools and laboratory models determines the progress in understanding mechanisms of virus emergence and pathogenesis. Recent large scale outbreaks of Zika virus (ZIKV) that were linked to complications during perinatal development and Guillain-Barre syndrome in adults emphasize the urgency for the development of a reverse-genetics system based on an epidemic ZIKV strain. Here, we report a stable infectious cDNA clone for ZIKV isolated during the 2015 epidemic in Brazil, as well as a Vero cell-adapted version of it, which will be used for virus-host interaction studies and vaccine development. PMID- 27555312 TI - A Role for Nuclear F-Actin Induction in Human Cytomegalovirus Nuclear Egress. AB - Herpesviruses, which include important pathogens, remodel the host cell nucleus to facilitate infection. This remodeling includes the formation of structures called replication compartments (RCs) in which herpesviruses replicate their DNA. During infection with the betaherpesvirus, human cytomegalovirus (HCMV), viral DNA synthesis occurs at the periphery of RCs within the nuclear interior, after which assembled capsids must reach the inner nuclear membrane (INM) for translocation to the cytoplasm (nuclear egress). The processes that facilitate movement of HCMV capsids to the INM during nuclear egress are unknown. Although an actin-based mechanism of alphaherpesvirus capsid trafficking to the INM has been proposed, it is controversial. Here, using a fluorescently-tagged, nucleus localized actin-binding peptide, we show that HCMV, but not herpes simplex virus 1, strongly induced nuclear actin filaments (F-actin) in human fibroblasts. Based on studies using UV inactivation and inhibitors, this induction depended on viral gene expression. Interestingly, by 24 h postinfection, nuclear F-actin formed thicker structures that appeared by super-resolution microscopy to be bundles of filaments. Later in infection, nuclear F-actin primarily localized along the RC periphery and between the RC periphery and the nuclear rim. Importantly, a drug that depolymerized nuclear F-actin caused defects in production of infectious virus, capsid accumulation in the cytoplasm, and capsid localization near the nuclear rim, without decreasing capsid accumulation in the nucleus. Thus, our results suggest that for at least one herpesvirus, nuclear F-actin promotes capsid movement to the nuclear periphery and nuclear egress. We discuss our results in terms of competing models for these processes. IMPORTANCE: The mechanisms underlying herpesvirus nuclear egress have not been fully determined. In particular, how newly assembled capsids move to the inner nuclear membrane for envelopment is uncertain and controversial. In this study, we show that HCMV, an important human pathogen, induces actin filaments in the nuclei of infected cells and that an inhibitor of nuclear F-actin impairs nuclear egress and capsid localization toward the nuclear periphery. Herpesviruses are widespread pathogens that cause or contribute to an array of human diseases. A better understanding of how herpesvirus capsids traffic in the nucleus may uncover novel targets for antiviral intervention and elucidate aspects of the nuclear cytoskeleton, about which little is known. PMID- 27555314 TI - The "virtual" obstetrical intensive care unit: providing critical care for contemporary obstetrics in nontraditional locations. AB - Management of the critically ill pregnant patient presents a clinical dilemma in which there are sparse objective data to determine the optimal setting for provision of high-quality care to these patients. This clinical scenario will continue to present a challenge for providers as the chronic illness and comorbid conditions continue to become more commonly encountered in the obstetric population. Various care models exist across a broad spectrum of facilities that are characterized by differing levels of resources; however, no studies have identified which model provides the highest level of care and patient safety while maintaining a reasonable degree of cost-effectiveness. The health care needs of the critically ill obstetric patient calls for clinicians to move beyond the traditional definition of the intensive care unit and develop a well-rounded, quickly responsive, and communicative interdisciplinary team that can provide high-quality, unique, and versatile care that best meets the needs of each particular patient. We propose a model in which a virtual intensive care unit team composed of preselected specialists from multiple disciplines (maternal fetal medicine, neonatology, obstetric anesthesiology, cardiology, pulmonology, etc) participate in the provision of individualized, precontemplated care that is readily adapted to the specific patient's clinical needs, regardless of setting. With this team-based approach, an environment of trust and familiarity is fostered among team members and well thought-out patient care plans are developed through routine prebrief discussions regarding individual clinical care for parturients anticipated to required critical care services. Incorporating debriefings between team members following these intricate cases will allow for the continued evolution of care as the medical needs of this patient population change as well. PMID- 27555313 TI - A Novel Erythrocyte Binding Protein of Plasmodium vivax Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes. AB - Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. In Plasmodium vivax, the interaction between the Duffy binding protein (DBP) and its cognate receptor, the Duffy antigen receptor for chemokines (DARC), on human erythrocytes is central to blood-stage infection. Contrary to this established pathway of invasion, there is growing evidence of P. vivax infections occurring in Duffy blood group-negative individuals, suggesting that the parasite might have gained an alternative pathway to infect this group of individuals. Supporting this concept, a second distinct erythrocyte binding protein (EBP2), representing a new member of the DBP family, was discovered in P. vivax and may be the ligand in an alternate invasion pathway. Our study characterizes this novel ligand and determines its potential role in reticulocyte invasion by P. vivax merozoites. EBP2 binds preferentially to young (CD71(high)) Duffy-positive (Fy(+)) reticulocytes and has minimal binding capacity for Duffy-negative reticulocytes. Importantly, EBP2 is antigenically distinct from DBP and cannot be functionally inhibited by anti-DBP antibodies. Consequently, our results do not support EBP2 as a ligand for invasion of Duffy-negative blood cells, but instead, EBP2 may represent a novel ligand for an alternate invasion pathway of Duffy-positive reticulocytes. IMPORTANCE: For decades, P. vivax infections in humans have been defined by a unique requirement for the interaction between the Duffy binding protein ligand of the parasite and the Duffy blood group antigen receptor (DARC). Recent reports of P. vivax infections in Duffy-negative individuals challenge this paradigm and suggest an alternate pathway of infection, potentially using the recently discovered EBP2. However, we demonstrate that EBP2 host cell specificity is more restricted than DBP binding and that EBP2 binds preferentially to Duffy-positive, young reticulocytes. This finding indicates that this DBP paralog does mediate a Duffy-independent pathway of infection. PMID- 27555315 TI - The combination tocolytic effect of magnesium sulfate and an oxytocin receptor antagonist in myometrium from singleton and twin pregnancies. AB - BACKGROUND: Preterm birth at <37 weeks of gestation is the most common and costly complication of pregnancy and remains the leading cause of neonatal morbidity, death, and reduced achievement in surviving infants. Magnesium sulfate is 1 class of tocolytics for threatened preterm labor; however, its clinical efficacy has been questioned. Twin pregnancies are at increased risk of preterm delivery compared with singleton gestations, which suggests that there is twin-specific risk to preterm delivery in twins. The prevention strategies that are applied to singleton pregnancies, however, have not been shown to be effective in twin pregnancies. OBJECTIVE: The purpose of this study was to compare the relaxant effect of magnesium sulfate on spontaneous and oxytocin-augmented contractions of human myometrium from singleton and twin pregnancies and to examine whether the effect of oxytocin on magnesium sulfate's potency could be reversed with the use of the oxytocin receptor antagonist, atosiban. STUDY DESIGN: Myometrium was obtained at the time of prelabor cesarean section (36-40 weeks of gestation) from women with singleton (n=23) or twin (n=12) pregnancy. Isometric tension recordings were made on myometrial strips that were mounted in organ baths that were superfused with physiologic saline solution. Strips were exposed to rising concentrations of magnesium sulfate, and the effect on spontaneous contractions or stimulated with oxytocin (0.5 nmol/L) and in the presence or absence of atosiban (100 nmol/L) was recorded. The contractile characteristics after each application of magnesium sulfate, which included amplitude of contraction and activity integral, were measured. Concentration-response curves were fitted with the use of nonlinear regression and comparison of the negative logarithm of the 50% reduction in activity values. RESULTS: Magnesium sulfate exerted an equal concentration-dependent inhibitory effect on spontaneous myometrial contractions from both singleton and twin myometrium (P>.05). The application of oxytocin produced a significant rightward shift in the concentration-response curves (P<.0001), but no differences were found between pregnancy groups (P>.05). The addition of atosiban shifted concentration-response curves significantly back to the left for amplitude of contraction and activity integral in singletons (P<.0001). However, only activity integral was significantly reversed in twins (P<.01). CONCLUSION: Magnesium sulfate is equipotent in suppressing contractions in singleton and twin myometrium. Oxytocin (0.5 nmol/L) significantly reduces the tocolytic potency of magnesium sulfate, which may explain, in part, magnesium sulfate's poor efficacy in vivo; however, this can be reversed partially by the use of an oxytocin receptor antagonist. Combination tocolysis that involves oxytocin receptor antagonists requires further investigation. PMID- 27555316 TI - Effect of letrozole on moderate and severe early-onset ovarian hyperstimulation syndrome in high-risk women: a prospective randomized trial. AB - BACKGROUND: Ovarian hyperstimulation syndrome is an iatrogenic complication of controlled ovarian stimulation. Early ovarian hyperstimulation syndrome occurs during luteal phase of controlled ovarian stimulation within 9 days after human chorionic gonadotropin trigger and reflects an acute consequence of this hormone on the ovaries. Late ovarian hyperstimulation syndrome occurs 10 or more days after human chorionic gonadotropin trigger and reflects increased endogenous human chorionic gonadotropin levels following pregnancy. Human chorionic gonadotropin stimulates granulosa-lutein cells to produce vascular endothelial growth factor messenger RNAs, which in turn raises serum vascular endothelial growth factor concentration and increases vascular permeability in women with ovarian hyperstimulation syndrome. Efforts to reduce the incidence and severity of ovarian hyperstimulation syndrome after oocyte retrieval, and in particular primary prevention efforts, are vital to prevent thrombogenesis and other serious complications. OBJECTIVE: The objective of the study was to compare the efficacy of letrozole, an aromatase inhibitor, with aspirin in primary prevention of early ovarian hyperstimulation syndrome and to compare vascular endothelial growth factor levels between groups. STUDY DESIGN: Participants in this prospective randomized trial included 238 participants undergoing cryopreservation of the whole embryos after oocyte retrieval with at least 1 of the following high-risk factors for ovarian hyperstimulation syndrome: oocyte retrieval >=25; estradiol level >=5000 pg/mL on the day of human chorionic gonadotropin administration; and clinical or ultrasonographic evidence of ovarian hyperstimulation syndrome on the day of oocyte retrieval, such as ultrasonographic evidence of ascites. After human chorionic gonadotropin triggering, experimental (119 cases) and control (119 cases) groups received letrozole and aspirin, respectively, for 5 days. The 5 categories of ovarian hyperstimulation syndrome include no, yes-mild, yes moderate, yes-severe, and yes-critical. The primary outcome was the incidence and severity of early ovarian hyperstimulation syndrome. The secondary outcome included vascular endothelial growth factor level both on the second and seventh day after the human chorionic gonadotropin trigger, and clinical and laboratory features of ovarian hyperstimulation syndrome symptoms. RESULTS: The incidence of ovarian hyperstimulation syndrome was significantly higher in women receiving aspirin, compared with letrozole (90.2% vs 80.4%, P = .044). Moderate and severe ovarian hyperstimulation syndrome was also higher in the aspirin group, 45.1%, compared with the letrozole group, 25.0% (P = .002). Moreover, the duration of luteal phase was shortened in letrozole group compared with aspirin group (8.1 +/ 1.1 days vs 10.5 +/- 1.9 days, P < .001). The vascular endothelial growth factor level was significantly higher in the letrozole-treated group than aspirin treated group (0.49 +/- 0.26 vs 0.42 +/- 0.22, P = .029). CONCLUSION: Letrozole was more effective than aspirin in decreasing the incidence of moderate and severe early-onset ovarian hyperstimulation syndrome. Our results indicate that ovarian hyperstimulation syndrome might be caused through a luteolytic effect rather than through modulation of vascular endothelial growth factor, racing by a decline in estradiol and termination of early-onset ovarian hyperstimulation syndrome in advance in high-risk women with cryopreservation of the whole embryos. PMID- 27555317 TI - Exercise during pregnancy and risk of cesarean delivery in nulliparous women: a large population-based cohort study. AB - BACKGROUND: Vaginal delivery for the first birth is of great importance for further obstetric performance for the individual woman. Given the rising cesarean delivery rates worldwide over the past decades, a search for modifiable factors that are associated with cesarean delivery is needed. Exercise may be a modifiable factor that is associated with type of delivery, but the results of previous studies are not conclusive. OBJECTIVE: The purpose of this study was to investigate the association between exercise during pregnancy and cesarean delivery, both acute and elective, in nulliparous women. STUDY DESIGN: We conducted a population-based cohort study that involved 39,187 nulliparous women with a singleton pregnancy who were enrolled in the Norwegian Mother and Child Cohort Study between 2000 and 2009. All women answered 2 questionnaires in pregnancy weeks 17 and 30. Acute and elective cesarean delivery data were obtained from the Medical Birth Registry of Norway. Information on exercise frequency and type was assessed prospectively by questionnaires in pregnancy weeks 17 and 30. Generalized linear models estimated risk differences of acute and elective cesarean delivery for different frequencies and types of exercise during pregnancy weeks 17 and 30. We used restricted cubic splines to examine dose-response associations of exercise frequency and acute cesarean delivery. A test for nonlinearity was also conducted. RESULTS: The total cesarean delivery rate was 15.4% (n=6030), of which 77.8% (n=4689) was acute cesarean delivery. Exercise during pregnancy was associated with a reduced risk of cesarean delivery, particularly for acute cesarean delivery. A nonlinear association was observed for exercise frequency in weeks 17 and 30 and risk of acute cesarean delivery (test for nonlinearity, P=.003 and P=.027, respectively). The largest risk reduction was observed for acute cesarean delivery among women who exercised >5 times weekly during weeks 17 (-2.2%) and 30 (-3.6%) compared with nonexercisers (test for trend, P<.001). Reporting high impact exercises in weeks 17 and 30 was associated with the greatest reduction in risk of acute cesarean delivery (-3.0% and -3.4%, respectively). CONCLUSION: Compared with nonexercisers, regular exercise and high-impact exercises during pregnancy are associated with reduced risk of having an acute cesarean delivery in first-time mothers. PMID- 27555318 TI - The interaction between maternal race/ethnicity and chronic hypertension on preterm birth. AB - BACKGROUND: In both the biomedical and public health literature, the risk for preterm birth has been linked to maternal racial/ethnic background, in particular African-American heritage. Despite this well-documented health disparity, the relationship of comorbid conditions, such as chronic hypertension, to maternal race/ethnicity and preterm birth has received relatively limited attention in the literature. OBJECTIVE: The objective of the study was to evaluate the interaction between chronic hypertension and maternal racial/ethnic background on preterm birth. STUDY DESIGN: This is a retrospective cohort study of singleton pregnancies among women who delivered between 2002 and 2015 at the University of California, San Francisco. The associations of chronic hypertension with both spontaneous and medically indicated preterm birth were examined by univariate and multivariate logistical regression, adjusting for confounders including for maternal age, history of preterm birth, maternal body mass index, insurance type (public vs private), smoking, substance abuse, history of pregestational diabetes mellitus, and use of assisted reproductive technologies. The interaction effect of chronic hypertension and racial/ethnicity was also evaluated. All values are reported as odds ratios, with 95% confidence intervals and significance set at P = .05. RESULTS: In this cohort of 23,425 singleton pregnancies, 8.8% had preterm deliveries (3% were medically indicated preterm birth, whereas 5.5% were spontaneous preterm births), and 3.8% of women carried the diagnosis of chronic hypertension. Chronic hypertension was significantly associated with preterm birth in general (adjusted odds ratio, 2.74, P < .001) and medically indicated preterm birth specifically (adjusted odds ratio, 5.25, P < .001). When evaluating the effect of chronic hypertension within racial/ethnic groups, there was an increased odds of a preterm birth among hypertensive, African-American women (adjusted odds ratio, 3.91, P < .001) and hypertensive, Asian-American/Pacific Islander women (adjusted odds ratio, 3.51, P < .001) when compared with their nonhypertensive counterparts within the same racial/ethnic group. These significant effects were also noted with regard to medically indicated preterm birth for hypertensive African-American women (adjusted odds ratio, 6.85, P < .001) and Asian-American/Pacific Islander women (adjusted odds ratio, 9.87, P < .001). There was no significant association of chronic hypertension with spontaneous preterm birth (adjusted odds ratio, 0.87, P = .4). CONCLUSION: The effect of chronic hypertension on overall preterm birth and medically indicated preterm birth differs by racial/ethnic group. The larger effect of chronic hypertension among African-American and Asian/Pacific Islander women on medically indicated and total preterm birth rates raises the possibility of an independent variable that is not captured in the data analysis, although data regarding the indication for medically indicated preterm delivery was limited in this data set. Further investigation into both social-structural and biological predispositions to preterm birth should accompany research focusing on the effect of chronic hypertension on birth outcomes. PMID- 27555319 TI - Maternofetal pharmacokinetics and fetal lung responses in chronically catheterized sheep receiving constant, low-dose infusions of betamethasone phosphate. AB - BACKGROUND: Antenatal steroids are standard of care for cases of anticipated preterm labor to improve neonatal outcomes. However, steroids are potent drugs, and their use in pregnancy remains largely unoptimized. OBJECTIVE: The objective of the study was to measure the maternofetal pharmacokinetics of constant, low dose intravenous betamethasone phosphate infusions and correlate these data with the transcriptional effect exerted by subclinical betamethasone exposures on the ovine fetal lung. STUDY DESIGN: Thirty-two ewes carrying a single fetus had surgery to catheterize fetal and maternal jugular veins at 116 days of gestation (term, 150 days). Animals were recovered for 2 days and then were randomized to receive 2 sequential maternal intravenous infusions of either (n = 4/group) of the following: 1) saline, 0.125, 0.04, or 0.0125 mg/kg betamethasone phosphate over 3 hours; or 2) saline, 0.25, 0.08, or 0.025 mg/kg betamethasone phosphate over 12 hours. Each infusion was separated by 2 days. Fetal lung tissue was collected for analysis using quantitative polymerase chain reaction and an ovine specific microarray. Plasma betamethasone levels from time-course catheter samples were determined by mass spectrometry. Data were assessed for distribution, variance, and tested by an analysis of variance. RESULTS: Betamethasone was detectable (>1 ng/mL) in fetal plasma only in animals randomized to 0.125 mg/kg 3 hour or 0.250 mg/kg 12 hour infusions. Fetal betamethasone half-lives were 1.7-2.8 times greater than maternal values. At maximum concentration, fetal plasma betamethasone levels were approximately 10% of maternal levels. Compared with saline control, all animals, other than those receiving 0.0125 mg/kg 3 hour betamethasone phosphate infusions, had evidence of dose-dependent glucocorticoid transcriptional responses in the fetal lung. CONCLUSION: Constant maternal betamethasone infusions delivering substantially lower fetal and maternal betamethasone maximal concentrations than those achieved with current clinical treatment protocols were associated with dose-dependent changes in glucocorticoid-response markers in the fetal lung. Further studies to determine the minimally efficacious dose of steroids for improving outcomes in preterm infants should be viewed as a priority. PMID- 27555320 TI - Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase iota. AB - DNA polymerase (pol) iota is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn2+ than Mg2+ The human germline R96G variant impairs both Mn2+-dependent and Mg2+-dependent activities of pol iota, whereas the Delta1-25 variant selectively enhances its Mg2+ dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol iota using pol iota core (residues 1-445) proteins. The presence of Mn2+ (0.15 mm) instead of Mg2+ (2 mm) caused a 770-fold increase in efficiency (kpol/Kd,dCTP) of pol iota for dCTP insertion opposite G, mainly due to a 450-fold decrease in Kd,dCTP The R96G and Delta1-25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in kpol/Kd,dCTP for dCTP insertion opposite G with Mg2+ when compared with wild type, substantially attenuated by substitution with Mn2+ Crystal structures of pol iota ternary complexes, including the primer terminus 3'-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg2+ or Mn2+, revealed that Mn2+ achieves more optimal octahedral coordination geometry than Mg2+, with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-pi interaction between both side chains. These results provide a mechanistic basis for alteration in pol iota catalytic function with coordinating metals and genetic variation. PMID- 27555321 TI - Allosteric Regulation of Mammalian Pantothenate Kinase. AB - Pantothenate kinase is the master regulator of CoA biosynthesis and is feedback inhibited by acetyl-CoA. Comparison of the human PANK3.acetyl-CoA complex to the structures of PANK3 in four catalytically relevant complexes, 5'-adenylyl beta,gamma-imidodiphosphate (AMPPNP).Mg2+, AMPPNP.Mg2+.pantothenate, ADP.Mg2+.phosphopantothenate, and AMP phosphoramidate (AMPPN).Mg2+, revealed a large conformational change in the dimeric enzyme. The amino-terminal nucleotide binding domain rotates to close the active site, and this allows the P-loop to engage ATP and facilitates required substrate/product interactions at the active site. Biochemical analyses showed that the transition between the inactive and active conformations, as assessed by the binding of either ATP.Mg2+ or acyl-CoA to PANK3, is highly cooperative indicating that both protomers move in concert. PANK3(G19V) cannot bind ATP, and biochemical analyses of an engineered PANK3/PANK3(G19V) heterodimer confirmed that the two active sites are functionally coupled. The communication between the two protomers is mediated by an alpha-helix that interacts with the ATP-binding site at its amino terminus and with the substrate/inhibitor-binding site of the opposite protomer at its carboxyl terminus. The two alpha-helices within the dimer together with the bound ligands create a ring that stabilizes the assembly in either the active closed conformation or the inactive open conformation. Thus, both active sites of the dimeric mammalian pantothenate kinases coordinately switch between the on and off states in response to intracellular concentrations of ATP and its key negative regulators, acetyl(acyl)-CoA. PMID- 27555322 TI - Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae. AB - Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6 ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. PMID- 27555323 TI - Substrate Affinity Differentially Influences Protein Kinase C Regulation and Inhibitor Potency. AB - The overlapping network of kinase-substrate interactions provides exquisite specificity in cell signaling pathways, but also presents challenges to our ability to understand the mechanistic basis of biological processes. Efforts to dissect kinase-substrate interactions have been particularly limited by their inherently transient nature. Here, we use a library of FRET sensors to monitor these transient complexes, specifically examining weak interactions between the catalytic domain of protein kinase Calpha and 14 substrate peptides. Combining results from this assay platform with those from standard kinase activity assays yields four novel insights into the kinase-substrate interaction. First, preferential binding of non-phosphorylated versus phosphorylated substrates leads to enhanced kinase-specific activity. Second, kinase-specific activity is inversely correlated with substrate binding affinity. Third, high affinity substrates can suppress phosphorylation of their low affinity counterparts. Finally, the substrate-competitive inhibitor bisindolylmaleimide I displaces low affinity substrates more potently leading to substrate selective inhibition of kinase activity. Overall, our approach complements existing structural and biophysical approaches to provide generalizable insights into the regulation of kinase activity. PMID- 27555324 TI - A Novel Role of Chromodomain Protein CBX8 in DNA Damage Response. AB - Induction of DNA damage induces a dynamic repair process involving DNA repair factors and epigenetic regulators. Chromatin alterations must occur for DNA repair factors to gain access to DNA lesions and restore original chromatin configuration to preserve the gene expression profile. We characterize the novel role of CBX8, a chromodomain-containing protein with established roles in epigenetic regulation in DNA damage response. CBX8 protein rapidly accumulates at the sites of DNA damage within 30 s and progresses to accumulate until 4 min before gradually dispersing back to its predamage distribution by 15 min. CBX8 recruitment to the sites of DNA damage is dependent upon PARP1 activation and not dependent on ATM activation. CBX8 biochemically interacts with TRIM33, and its recruitment to DNA damage is also dependent on the presence of TRIM33. Knockdown of CBX8 using siRNA significantly reduces the efficiency of both homologous and the other non-homologous recombination, as well as increases sensitivity of cells to ionizing radiation. These findings demonstrate that CBX8 functions in the PARP dependent DNA damage response partly through interaction with TRIM33 and is required for efficient DNA repair. PMID- 27555325 TI - Anthrax Toxin Protective Antigen Variants That Selectively Utilize either the CMG2 or TEM8 Receptors for Cellular Uptake and Tumor Targeting. AB - The protective antigen (PA) moiety of anthrax toxin binds to cellular receptors and mediates the translocation of the two enzymatic moieties of the toxin to the cytosol. Two PA receptors are known, with capillary morphogenesis protein 2 (CMG2) being the more important for pathogenesis and tumor endothelial marker 8 (TEM8) playing a minor role. The C-terminal PA domain 4 (PAD4) has extensive interactions with the receptors and is required for binding. Our previous study identified PAD4 variants having enhanced TEM8 binding specificity. To obtain PA variants that selectively bind to CMG2, here we performed phage display selections using magnetic beads having bound CMG2. We found that PA residue isoleucine 656 plays a critical role in PA binding to TEM8 but has a much lesser effect on PA binding to CMG2. We further characterized the role of residue 656 in distinguishing PA binding to CMG2 versus TEM8 by substituting it with the other 19 amino acids. Of the resulting variants, PA I656Q and PA I656V had significantly reduced activity on TEM8-expressing CHO cells but maintained their activity on CMG2-expressing CHO cells. The preference of these PA mutants for CMG2 over TEM8 was further demonstrated using mouse embryonic fibroblast cells and mice deficient in the CMG2 and/or the TEM8 receptors. The structural basis of the alterations in the receptor binding activities of these mutants is also discussed. PMID- 27555326 TI - Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells. AB - A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function. PMID- 27555327 TI - Structural and Functional Basis for Lipid Synergy on the Activity of the Antibacterial Peptide ABC Transporter McjD. AB - The lipid bilayer is a dynamic environment that consists of a mixture of lipids with different properties that regulate the function of membrane proteins; these lipids are either annular, masking the protein hydrophobic surface, or specific lipids, essential for protein function. In this study, using tandem mass spectrometry, we have identified specific lipids associated with the Escherichia coli ABC transporter McjD, which translocates the antibacterial peptide MccJ25. Using non-denaturing mass spectrometry, we show that McjD in complex with MccJ25 survives the gas phase. Partial delipidation of McjD resulted in reduced ATPase activity and thermostability as shown by circular dichroism, both of which could be restored upon addition of defined E. coli lipids. We have resolved a phosphatidylglycerol lipid associated with McjD at 3.4 A resolution, whereas molecular dynamic simulations carried out in different lipid environments assessed the binding of specific lipids to McjD. Combined, our data show a synergistic effect of zwitterionic and negatively charged lipids on the activity of McjD; the zwitterionic lipids provide structural stability to McjD, whereas the negatively charged lipids are essential for its function. PMID- 27555329 TI - Fe-Catalyzed Aerobic Oxidative C-CN Bond Cleavage of Arylacetonitriles Leading to Various Esters. AB - Fe-catalyzed aerobic oxidative esterifications of arylacetonitriles with alcohols, tri alkoxsilanes, silicate esters, or borate esters have been developed. The acyl groups which were in situ generated via chemoselective C(CO) CN bond cleavage were directly used as electrophiles, leading to corresponding aryl esters in good to excellent yields under molecular oxygen when attacked by alcohols or alcohol surrogates. Dioxygen serves as both oxidant and reactant in this protocol. The reaction has a very broad substrate scope. Cheap starting materials as well as environmentally benign and inexpensive iron catalyst and ideal oxidant O2 feature this transformation and make it a practical and sustainable protocol to afford esters. PMID- 27555331 TI - Emerging Research on Orofacial Pain. PMID- 27555330 TI - Assembled molecular face-rotating polyhedra to transfer chirality from two to three dimensions. AB - In nature, protein subunits on the capsids of many icosahedral viruses form rotational patterns, and mathematicians also incorporate asymmetric patterns into faces of polyhedra. Chemists have constructed molecular polyhedra with vacant or highly symmetric faces, but very little is known about constructing polyhedra with asymmetric faces. Here we report a strategy to embellish a C3h truxene unit with rotational patterns into the faces of an octahedron, forming chiral octahedra that exhibit the largest molar ellipticity ever reported, to the best of our knowledge. The directionalities of the facial rotations can be controlled by vertices to achieve identical rotational directionality on each face, resembling the homo-directionality of virus capsids. Investigations of the kinetics and mechanism reveal that non-covalent interaction among the faces is essential to the facial homo-directionality. PMID- 27555333 TI - alpha-Glucosidase inhibitory activity, molecular docking, QSAR and ADMET properties of novel 2-amino-phenyldiazenyl-4H-chromene derivatives. PMID- 27555332 TI - Fear of Pain Mediates the Association between MC1R Genotype and Dental Fear. AB - Fear of pain is experienced in acute and chronic pain populations, as well as in the general population, and it affects numerous aspects of the orofacial pain experience, including pain intensity, pain-related disability, and pain behavior (e.g., avoidance). A related but separate construct-dental fear-is also experienced in the general population, and it influences dental treatment-seeking behavior and oral and systemic health. Minimal work has addressed the role of genetics in the etiologies of fear of pain and dental fear. Limited available data suggest that variants of the melanocortin 1 receptor (MC1R) gene may predict greater levels of dental fear. The MC1R gene also may be etiologically important for fear of pain. This study aimed to replicate the finding that MC1R variant status predicts dental fear and to determine, for the first time, whether MC1R variant status predicts fear of pain. Participants were 817 Caucasian participants (62.5% female; mean +/- SD age: 34.7 +/- 8.7 y) taking part in a cross-sectional project that identified determinants of oral diseases at the community, family, and individual levels. Participants were genotyped for single nucleotide polymorphisms on MC1R and completed self-report measures of fear of pain and dental fear. Presence of MC1R variant alleles predicted higher levels of dental fear and fear of pain. Importantly, fear of pain mediated the relation between MC1R variant status and dental fear (B = 1.60, 95% confidence interval: 0.281 to 3.056). MC1R variants may influence orofacial pain perception and, in turn, predispose individuals to develop fears about pain. Such fears influence the pain experience and associated pain behaviors, as well as fears about dental treatment. This study provides support for genetic contributions to the development/maintenance of fear of pain and dental fear, and it offers directions for future research to identify potential targets for intervention in the treatment of fear of pain and dental fear. PMID- 27555328 TI - Liberating Chiral Lipid Mediators, Inflammatory Enzymes, and LIPID MAPS from Biological Grease. AB - In 1970, it was well accepted that the central role of lipids was in energy storage and metabolism, and it was assumed that amphipathic lipids simply served a passive structural role as the backbone of biological membranes. As a result, the scientific community was focused on nucleic acids, proteins, and carbohydrates as information-containing molecules. It took considerable effort until scientists accepted that lipids also "encode" specific and unique biological information and play a central role in cell signaling. Along with this realization came the recognition that the enzymes that act on lipid substrates residing in or on membranes and micelles must also have important signaling roles, spurring curiosity into their potentially unique modes of action differing from those acting on water-soluble substrates. This led to the creation of the concept of "surface dilution kinetics" for describing the mechanism of enzymes acting on lipid substrates, as well as the demonstration that lipid enzymes such as phospholipase A2 (PLA2) contain allosteric activator sites for specific phospholipids as well as for membranes. As our understanding of phospholipases advanced, so did the understanding that many of the lipids released by these enzymes are chiral information-containing signaling molecules; for example, PLA2 regulates the generation of precursors for the biosynthesis of eicosanoids and other bioactive lipid mediators of inflammation and resolution underlying disease progression. The creation of the LIPID MAPS initiative in 2003 and the ensuing development of the lipidomics field have revealed that lipid metabolites are central to human metabolism. Today lipids are recognized as key mediators of health and disease as we enter a new era of biomarkers and personalized medicine. This article is my personal "reflection" on these scientific advances. PMID- 27555334 TI - Reversible FMN dissociation from Escherichia coli respiratory complex I. AB - Respiratory complex I transfers electrons from NADH to quinone, utilizing the reaction energy to translocate protons across the membrane. It is a key enzyme of the respiratory chain of many prokaryotic and most eukaryotic organisms. The reversible NADH oxidation reaction is facilitated in complex I by non-covalently bound flavin mononucleotide (FMN). Here we report that the catalytic activity of E. coli complex I with artificial electron acceptors potassium ferricyanide (FeCy) and hexaamineruthenium (HAR) is significantly inhibited in the enzyme pre reduced by NADH. Further, we demonstrate that the inhibition is caused by reversible dissociation of FMN. The binding constant (Kd) for FMN increases from the femto- or picomolar range in oxidized complex I to the nanomolar range in the NADH reduced enzyme, with an FMN dissociation time constant of ~5s. The oxidation state of complex I, rather than that of FMN, proved critical to the dissociation. Such dissociation is not observed with the T. thermophilus enzyme and our analysis suggests that the difference may be due to the unusually high redox potential of Fe-S cluster N1a in E. coli. It is possible that the enzyme attenuates ROS production in vivo by releasing FMN under highly reducing conditions. PMID- 27555335 TI - How long and what does it take for physical and emotional recovery after heart surgery? PMID- 27555336 TI - Blue-black pigmentation of heart valves. Is it as evil as it looks? PMID- 27555337 TI - Yes, minimally invasive left ventricular device implantation can be done-but should it? PMID- 27555338 TI - Scallops, fenestrations, CHIMPS, and other monkey business. PMID- 27555339 TI - The tail wagging the dog: Attention to detail in valvular surgery. PMID- 27555340 TI - Prevention and management of sternal wound infections. PMID- 27555341 TI - Erratum: Stiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density. PMID- 27555342 TI - Are international medical graduates well supported by the emergency medicine community in Australasia? Yes. PMID- 27555343 TI - Photorhabdus-nematode symbiosis is dependent on hfq-mediated regulation of secondary metabolites. AB - Photorhabdus luminescens maintains a symbiotic relationship with the nematodes Heterorhabditis bacteriophora and together they infect and kill insect larvae. To maintain this symbiotic relationship, the bacteria must produce an array of secondary metabolites to assist in the development and replication of nematodes. The regulatory mechanisms surrounding production of these compounds are mostly unknown. The global post-transcriptional regulator, Hfq, is widespread in bacteria and performs many functions, one of which is the facilitation of sRNA binding to target mRNAs, with recent research thoroughly exploring its various pleiotropic effects. Here we generate and characterize an hfq deletion mutant and show that in the absence of hfq, the bacteria are no longer able to maintain a healthy symbiosis with nematodes due to the abolishment of the production of all known secondary metabolites. RNAseq led us to produce a second deletion of a known repressor, HexA, in the same strain, which restored both metabolite production and symbiosis. PMID- 27555344 TI - The dorsal pancreatic artery in pancreas procurement and transplantation: anatomical considerations and potential implications. AB - AIM: Organ procurement errors account for almost 20% of discarded pancreatic allografts. For this reason, the anatomical significance of the dorsal pancreatic artery (DPA) was reviewed. METHODS: A strategy on dealing with an often overlooked DPA is evaluated. RESULTS: The DPA provides together with the splenic artery the main blood supply to the pancreatic tail. Three different arterial variations have been described. In the rare instances when the DPA arises from the common hepatic artery or the celiac trunk, instead of the splenic origin, the DPA can easily be overlooked by surgeons not familiar with this artery. This may result in an unintentional damage to the pancreatic tail blood supply. If unrecognized during the back-table inspection, it could potentially jeopardize the pancreatic graft after reperfusion. When a cut DPA is encountered during inspection, efforts should be attempted to revascularize the graft, especially if there is no backflow from the splenic artery as sign of absent collateral circulation. CONCLUSION: The DPA may play a more prominent role in the vascularization of pancreas transplants than currently assumed. Better understanding of the vascular anatomy may lead to improved results in pancreas transplantation. PMID- 27555345 TI - Mangifera sylvatica (Wild Mango): A new cocoa butter alternative. AB - Cocoa butter is the pure butter extracted from cocoa beans and is a major ingredient in the chocolate industry. Global production of cocoa is in decline due to crop failure, diseases and ageing plantations, leading to price fluctuations and the necessity for the industry to find high quality cocoa butter alternatives. This study explored the potential of a wild mango (Mangifera sylvatica), an underutilised fruit in south-east Asia, as a new Cocoa Butter Alternative (CBA). Analyses showed that wild mango butter has a light coloured fat with a similar fatty acid profile (palmitic, stearic and oleic acid) and triglyceride profile (POP, SOS and POS) to cocoa butter. Thermal and physical properties are also similar to cocoa butter. Additionally, wild mango butter comprises 65% SOS (1, 3-distearoyl-2-oleoyl-glycerol) which indicates potential to become a Cocoa Butter Improver (an enhancement of CBA). It is concluded that these attractive properties of wild mango could be prompted by a coalition of policy makers, foresters, food industries and horticulturists to promote more widespread cultivation of this wild fruit species to realise the market opportunity. PMID- 27555346 TI - Somatic Genome Editing Goes Viral. AB - Generating new mouse models of cancer is a challenging and laborious task that can require years of investment to interrogate a single gene. Now, Jonkers and colleagues describe the first application of CRISPR-based genome editing in the mammary gland, providing a new approach to dissect complex genetic interactions in vivo. PMID- 27555347 TI - NRF2: Translating the Redox Code. AB - Cancer requires mechanisms to mitigate reactive oxygen species (ROS) generated during rapid growth, such as induction of the antioxidant transcription factor, Nrf2. However, the targets of ROS-mediated cytotoxicity are unclear. Recent studies in pancreatic cancer show that redox control by Nrf2 prevents cysteine oxidation of the mRNA translational machinery, thereby supporting efficient protein synthesis. PMID- 27555348 TI - Corrigendum to "Expert consensus paper on the use of Vedolizumab for the management of patients with moderate-to-severe Inflammatory Bowel Disease" [Dig. Liver Dis. 48 (2016) 360-370]. PMID- 27555349 TI - [Evolution of the non-conformities of prescriptions of labile blood products after awareness the physician in the department of Indre (France)]. PMID- 27555350 TI - Soluble epoxide hydrolase inhibitory components from Rheum undulatum and in silico approach. AB - Continuous efforts to identify sEH inhibitors using activity-guided fractionation have revealed 12 known compounds, 2-13, from Rheum undulatum. Compounds 2-13 and 1, which was obtained from the in-house library, were tested for inhibitory activity against sEH. Compounds 1-9, 11, and 12 were shown to have inhibitory activity, with IC50 values ranging from 2.5 +/- 0.5 to 53.2 +/- 4.4 MUM. They were subjected to enzyme kinetic studies to explore the binding mode between the ligand and receptor. Based on our results, compounds 1, 2, 5-9, and 11 (mixed type) and compounds 3 and 12 (noncompetitive type) had a preferred allosteric site. Compound 4 was identified as a competitive-type interaction in the active site. Molecular docking studies revealed the interacting residues and binding energy between sEH and inhibitors. Additionally, molecular dynamics provided detailed information on the interaction between the ligand and receptor. PMID- 27555351 TI - Outcome of Minimally Invasive Open and Percutaneous Techniques for Repair of Calcaneal Fractures: A Systematic Review. AB - Percutaneous and minimally invasive open techniques for the treatment of calcaneal fractures are now frequently used with good results, although a comparison between these different techniques has not yet been performed. The aim of the present review was to search for studies evaluating the outcomes of patients after treatment with percutaneous and minimally invasive open techniques for calcaneal fractures. A search was performed using PubMed/MEDLINE, Embase, and the Cochrane Library. Studies from the previous 15 years in English were included. Data on the Sanders classification, operation technique, infection rate, American Orthopaedic Foot and Ankle Society ankle-hindfoot score, radiographic evaluation, and follow-up were extracted. The techniques were divided into 4 groups: minimally invasive open, percutaneous reduction and screw osteosynthesis, external fixation, and other. Forty-six studies were included, with 1776 patients and 2018 calcaneal fractures. Of the 2018 fractures, 924 (46%) were classified as Sanders II, 558 (28%) as Sanders III, and 245 (12%) as Sanders IV; the fractures of 291 patients(14%) were not classified or were classified as complete extra-articular. Of the 46 studies, 15 used a minimally invasive open technique, 19 evaluated the outcome of percutaneous reduction and screw osteosynthesis, 10 investigated the results of an external fixation system, and 2 studies used other operative techniques. The median infection rate was 3% (range 0% to 33%). The median American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 83 (range 67 to 94). The median angle of Bohler postoperatively was 24 degrees (range 14 degrees to 35 degrees ) and had increased after operative treatment, with a median of 16 degrees (range 0 degrees to 39 degrees ). The percutaneous reduction and screw osteosynthesis and minimal invasive open technique resulted in significantly better outcomes compared with external fixation and other techniques. In conclusion, percutaneous reduction and screw osteosynthesis and minimal invasive open techniques have the best outcomes for the minimal invasive open surgical treatment of calcaneal fractures. PMID- 27555352 TI - Intraneural Lipoma of the Tibial Nerve: A Case Report. AB - Intraneural lipomas, neurofibrolipomas, lipofibromatous hamartomas, and perineural lipomas are subsets of hamartomas that typically present as fibroadipose, soft tissue masses within the epineurium of a nerve. Several cases involving intraneural lipomas of the median nerve in the upper extremity have been reported; however, owing to the lesion's rare incidence in the foot and ankle, only a select few cases involving the superficial peroneal nerve have been reported. We present the first case of a tibial nerve intraneural lipoma in a 42 year-old female with a follow-up period of 2 years. We discuss the clinical presentation, distinguishing features, surgical procedures, and short-term outcome regarding this unique tumor. PMID- 27555353 TI - Knotless Repair of Achilles Tendon Rupture in an Elite Athlete: Return to Competition in 18 Weeks. AB - Rupture of the Achilles tendon is an increasingly common injury, particularly in physically active males, and current evidence favors minimally invasive surgical repair. We describe the case of a 36-year-old male elite bobsled athlete with complete rupture of the Achilles tendon. He was treated with surgical repair of the ruptured tendon using an innovative, minimally invasive procedure based on an internal bracing concept and was able to undergo early mobilization and aggressive physiotherapy rehabilitation. His recovery was such that he returned to training at 13 weeks postoperatively and participated in an international competition at 18 weeks, winning a World Cup silver medal. He subsequently raced at the 2014 Winter Olympic Games at 29 weeks after surgery. At >2 years since his injury, he has experienced no complications or reinjury. This represents an exceptional recovery that far exceeds the standard expected for such injuries. The use of this technique for athletes could enable accelerated return to sporting activity and attainment of their preinjury activity levels. PMID- 27555354 TI - Reduced nicotine content cigarettes, e-cigarettes and the cigarette end game. PMID- 27555355 TI - Non-enhanced MR lymphography of the thoracic duct: improved visualization following ingestion of a high fat meal-initial experience. AB - PURPOSE: The objective of this study was to compare the clarity of magnetic resonance lymphography (MRL) images of the thoracic duct (TD) obtained from subjects following an overnight fast with those obtained from the same subjects after ingestion of a high fat meal. METHODS: Nineteen healthy volunteers were included in this study. TD images were acquired on a 3.0T MRI system with the imaging sequence of magnetic resonance cholangiopancreatography. TD MRL images were obtained from subjects following an overnight fast and from the same subjects 3-4 h after ingestion of a high fat meal. Images were displayed in maximum intensity projection format and degree of visualization was evaluated using a scoring system. RESULTS: The mean TD score obtained following an overnight fast was significantly lower than the mean TD score obtained 3-4 h after ingestion of a high fat meal (P<0.05). CONCLUSION: The clarity of TD MRL images is improved if subjects have ingested a high fat meal 3-4 h prior to examination. PMID- 27555356 TI - Development, structure, and maintenance of C. elegans body wall muscle. AB - In C. elegans, mutants that are defective in muscle function and/or structure are easy to detect and analyze since: 1) body wall muscle is essential for locomotion, and 2) muscle structure can be assessed by multiple methods including polarized light, electron microscopy (EM), Green Fluorescent Protein (GFP) tagged proteins, and immunofluorescence microscopy. The overall structure of the sarcomere, the fundamental unit of contraction, is conserved from C. elegans to man, and the molecules involved in sarcomere assembly, maintenance, and regulation of muscle contraction are also largely conserved. This review reports the latest findings on the following topics: the transcriptional network that regulates muscle differentiation, identification/function/dynamics of muscle attachment site proteins, regulation of the assembly and maintenance of the sarcomere by chaperones and proteases, the role of muscle-specific giant protein kinases in sarcomere assembly, and the regulation of contractile activity, and new insights into the functions of the dystrophin glycoprotein complex. PMID- 27555357 TI - Editorial Comment. PMID- 27555358 TI - Author Reply. PMID- 27555359 TI - Adverse Infant Outcomes Associated with Discordant Gestational Age Estimates. AB - BACKGROUND: Gestational age estimation by last menstrual period (LMP) vs. ultrasound (or best obstetric estimate in the US) may result in discrepant classification of preterm vs. term birth. We investigated whether such discrepancies are associated with adverse infant outcomes. METHODS: We studied singleton livebirths in the Medical Birth Registries of Norway, Sweden and Finland and US live birth certificates from 1999 to the most recent year available. Risk ratios (RR) with 95% confidence intervals (CI) by discordant and concordant gestational age estimation for infant, neonatal and post-neonatal mortality, Apgar score <4 and <7 at 5 min, and neonatal intensive care unit (NICU) admission were estimated using generalised linear models, adjusting for maternal age, education, parity, year of birth, and infant sex. Results were presented stratified by country. RESULTS: Compared to infants born at term by both methods, infants born preterm by ultrasound/best obstetric estimate but term by LMP had higher infant mortality risks (range of adjusted RRs 3.9 to 7.2) and modestly higher risks were obtained among infants born preterm by LMP but term by ultrasound/best obstetric estimate (range of adjusted RRs 1.6 to 1.9). Risk estimates for the other outcomes showed the same pattern. These findings were consistent across all four countries. CONCLUSIONS: Infants classified as preterm by ultrasound/best estimate, but term by LMP have consistently higher risks of adverse outcomes than those classified as preterm by LMP but term by ultrasound/best estimate. Compared with ultrasound/best estimate, use of LMP overestimates the proportion of births that are preterm. PMID- 27555360 TI - Noncoding RNA-regulated gain-of-function of STOX2 in Finnish pre-eclamptic families. AB - The familial forms of early onset pre-eclampsia and related syndromes (HELLP) present with hypertension and proteinuria in the mother and growth restriction of the fetus. Genetically, these clinically similar entities are caused by different founder-dependent, placentally-expressed paralogous genes. All susceptibility genes (STOX1, lincHELLP, INO80B) identified so far are master control genes that regulate an essential trophoblast differentiation pathway, but act at different entry points. Many genes remain to be identified. Here we demonstrate that a long non-coding RNA (lncRNA) within intron 3 of the STOX2 gene on 4q35.1 acts as a permissive cis-acting regulator of alternative splicing of STOX2. When this lncRNA is mutated or absent, an alternative exon (3B) of STOX2 is included. This introduces a stop codon resulting in the deletion of a highly conserved domain of 64 amino acids in the C-terminal of the STOX2 protein. A mutation present within a regulatory region within intron 1 of STOX2 has the same effect after blocking with CRISPR technology: transcripts with exon 3B are upregulated. This proces appears related to transcriptional control by a chromatin-splicing adaptor complex as described for FGFR2. For STOX2, CHD5, coding for a chromodomain helicase DNA binding protein, qualifies as the chromatin modifier in this process. PMID- 27555362 TI - MOF-5-Polystyrene: Direct Production from Monomer, Improved Hydrolytic Stability, and Unique Guest Adsorption. AB - An unprecedented mode of reactivity of Zn4 O-based metal-organic frameworks (MOFs) offers a straightforward and powerful approach to polymer-hybridized porous solids. The concept is illustrated with the production of MOF-5 polystyrene wherein polystyrene is grafted and uniformly distributed throughout MOF-5 crystals after heating in pure styrene for 4-24 h. The surface area and polystyrene content of the material can be fine-tuned by controlling the duration of heating styrene in the presence of MOF-5. Polystyrene grafting significantly alters the physical and chemical properties of pristine MOF-5, which is evident from the unique guest adsorption properties (solvatochromic dye uptake and improved CO2 capacity) as well as the dramatically improved hydrolytic stability of composite. Based on the fact that MOF-5 is the best studied member of the structure class, and has been produced at scale by industry, these findings can be directly leveraged for a range of current applications. PMID- 27555363 TI - Modulation of Inhibitory Processing by Posttraumatic Stress Symptoms and Anxiety in a Subclinical Sample of Children. AB - In adults, pathologies of anxiety such as posttraumatic stress symptoms (PTSS) involve deficits in information processing that may reflect hypervigilance and deficient inhibitory control, specifically for negative information. However, little is known about inhibitory processing in children, particularly regarding the inhibition of emotional information. This study investigated whether children with PTSS or anxiety show impairments in executive control in an inhibition task. A total of 45 children (M age = 9.2 year, SD = 0.7, range: 8-11) completed an inhibition task involving emotional-happy, angry, and fearful-and neutral stimuli and clinical scales for PTSS and anxiety. The results indicated that the percentage of correct answers was modulated by PTSS status, particularly in the happiness task. PTSS and anxiety altered the inhibition of fearful information in children. These data suggest different types of inhibitory deficits depending on clinical symptoms, and implications are discussed. PMID- 27555361 TI - White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder. AB - Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD and 44 typically developing (TD) age- and IQ-matched peers using diffusion tensor imaging. Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long-distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory. PMID- 27555364 TI - Mental Toughness, Emotional Intelligence, and Coping Effectiveness: An Analysis of Construct Interrelatedness Among High-Performing Adolescent Male Athletes. AB - The purpose of this study was to examine the interrelationships between mental toughness (MT) and two constructs also linked to athletic performance, emotional intelligence (EI) and coping effectiveness. A sample of 151 male adolescent athletes (M age = 15.4 years, SD = 1.3) completed the Sports Mental Toughness Questionnaire, the Self-Rated Emotional Intelligence Scale, and an adapted version of the Coping Effectiveness Scale. The regression and mediation analysis results supported both hypotheses in that (a) EI was a significant predictor of MT and (b) the relationship between EI and coping effectiveness was fully mediated by MT. The findings suggest that EI may be an important mechanism through which mentally tough responses and outcomes are generated. Furthermore, although EI is associated with coping effectiveness, it is the attributes of MT that account for the superior coping effectiveness reported among athletes high in EI. Future research could explore whether MT may be developed through intervention programs that target EI, along with the influence of such programs on athletes' coping effectiveness. PMID- 27555365 TI - Control Strategies for Accurate Force Generation and Relaxation. AB - Characteristics and motor strategies for force generation and force relaxation were examined using graded tasks during isometric force control. Ten female college students (M age = 20.2 yr., SD = 1.1) were instructed to accurately control the force of isometric elbow flexion using their right arm to match a target force level as quickly as possible. They performed: (1) a generation task, wherein they increased their force from 0% maximum voluntary force to 20% maximum voluntary force (0%-20%), 40% maximum voluntary force (0%-40%), or 60% maximum voluntary force (0%-60%) and (2) and a relaxation task, in which they decreased their force from 60% maximum voluntary force to 40% maximum voluntary force (60% 40%), 20% maximum voluntary force (60%-20%), or to 0% maximum voluntary force (60%-0%). Produced force parameters of point of accuracy (force level, error), quickness (reaction time, adjustment time, rate of force development), and strategy (force wave, rate of force development) were analyzed. Errors of force relaxation were all greater, and reaction times shorter, than those of force generation. Adjustment time depended on the magnitude of force and peak rates of force development and force relaxation differed. Controlled relaxation of force is more difficult with low magnitude of force control. PMID- 27555366 TI - Gaze Control in One Versus One Defensive Situations in Soccer Players With Various Levels of Expertise. AB - Experienced and less experienced soccer players were compared in terms of their gaze behavior (number of fixations, fixation duration, number of fixation regions, and distribution of fixations across specific regions) during frontal 1 vs. 1 defensive situations. Twenty-four men (eight experienced soccer players, eight less experienced players and eight non-players) watched 20 video clips. Gaze behavior was registered with an Eye Tracking System. The video scenes were analyzed frame-by-frame. Significant main effect of the group (experience) was observed for the number of fixation regions. Experienced soccer players had a lower number of fixation regions than the non-soccer players. Moreover, the former group presented with significantly larger percentage of fixations in the ball/foot region. These findings suggest that experienced players may use a more efficient search strategy than novices, involving fixation on a lesser number of areas in specific locations. PMID- 27555367 TI - Participation in Team Sports Can Eliminate the Effect of Social Loafing. AB - The effect known as Ringelmann effect states that as group size increases, individual behavior may be less productive. If this decrease in productivity in groups is attributed to a decrement in individual motivation, it is called social loafing. We tested hypotheses that the collectivism associated with participation in team sports would reduce the level of social loafing compared to people who were not involved in team sports. In one experiment, participants (n = 72; M age = 21.7 years, SD = 2.0) had to pull a rope individually and collectively. Groups of two, three, four, and six persons were formed from among individuals with no previous sports experience, and of those who had engaged in individual and team sports. For each team, the sum of individual achievements of the individuals constituting a team was computed. This sum served as the anticipated result (expected value). The expected values were later compared to the actual achievements, i.e., the value achieved by the whole team. The results of the study suggested that previous experience in collective (team) sports eliminated the effect of social loafing. PMID- 27555368 TI - The Simplest Chronoscope V: A Theory of Dual Primary and Secondary Reaction Time Systems. AB - Extending work by Montare, visual simple reaction time, choice reaction time, discriminative reaction time, and overall reaction time scores obtained from college students by the simplest chronoscope (a falling meterstick) method were significantly faster as well as significantly less variable than scores of the same individuals from electromechanical reaction timers (machine method). Results supported the existence of dual reaction time systems: an ancient primary reaction time system theoretically activating the V5 parietal area of the dorsal visual stream that evolved to process significantly faster sensory-motor reactions to sudden stimulations arising from environmental objects in motion, and a secondary reaction time system theoretically activating the V4 temporal area of the ventral visual stream that subsequently evolved to process significantly slower sensory-perceptual-motor reactions to sudden stimulations arising from motionless colored objects. PMID- 27555369 TI - Strains of the Propionibacterium acnes type III lineage are associated with the skin condition progressive macular hypomelanosis. AB - Progressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in a variety of skin types. Although the underlying aetiology of this condition is unclear, there is circumstantial evidence that links the skin bacterium Propionibacterium acnes to the condition. We now describe the first detailed population genetic analysis of P. acnes isolates recovered from paired lesional and non-lesional skin of PMH patients. Our results demonstrate a strong statistical association between strains from the type III phylogenetic lineage and PMH lesions (P = 0.0019), but not those representing other phylogroups, including those associated with acne (type IA1). We also demonstrate, based on in silico 16S rDNA analysis, that PMH isolates previously recovered from patients in Europe are also consistent with the type III lineage. Using comparative genome analysis, we identified multiple genomic regions that are specific for, or absent from, type III strains compared to other phylogroups. In the former case, these include open reading frames with putative functions in metabolism, transport and transcriptional regulation, as well as predicted proteins of unknown function. Further study of these genomic elements, along with transcriptional and functional analyses, may help to explain why type III strains are associated with PMH. PMID- 27555370 TI - Abundant Lysine Methylation and N-Terminal Acetylation in Sulfolobus islandicus Revealed by Bottom-Up and Top-Down Proteomics. AB - Protein post-translational methylation has been reported to occur in archaea, including members of the genus Sulfolobus, but has never been characterized on a proteome-wide scale. Among important Sulfolobus proteins carrying such modification are the chromatin proteins that have been described to be methylated on lysine side chains, resembling eukaryotic histones in that aspect. To get more insight into the extent of this modification and its dynamics during the different growth steps of the thermoacidophylic archaeon S. islandicus LAL14/1, we performed a global and deep proteomic analysis using a combination of high throughput bottom-up and top-down approaches on a single high-resolution mass spectrometer. 1,931 methylation sites on 751 proteins were found by the bottom-up analysis, with methylation sites on 526 proteins monitored throughout three cell culture growth stages: early-exponential, mid-exponential, and stationary. The top-down analysis revealed 3,978 proteoforms arising from 681 proteins, including 292 methylated proteoforms, 85 of which were comprehensively characterized. Methylated proteoforms of the five chromatin proteins (Alba1, Alba2, Cren7, Sul7d1, Sul7d2) were fully characterized by a combination of bottom-up and top down data. The top-down analysis also revealed an increase of methylation during cell growth for two chromatin proteins, which had not been evidenced by bottom up. These results shed new light on the ubiquitous lysine methylation throughout the S. islandicus proteome. Furthermore, we found that S. islandicus proteins are frequently acetylated at the N terminus, following the removal of the N-terminal methionine. This study highlights the great value of combining bottom-up and top down proteomics for obtaining an unprecedented level of accuracy in detecting differentially modified intact proteoforms. The data have been deposited to the ProteomeXchange with identifiers PXD003074 and PXD004179. PMID- 27555371 TI - Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin. AB - Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of articular cartilage. As chondrocytes are the only cell type forming the articular cartilage, their gradual loss is the main cause of OA. There is a substantial body of published research that suggests reactive oxygen species (ROS) are major causative factors for chondrocyte damage and OA development. Oxidative stress elicited by ROS is capable of oxidizing and subsequently disrupting cartilage homeostasis, promoting catabolism via induction of cell death and damaging numerous components of the joint. IL-1beta and TNF-alpha are crucial inflammatory factors that play pivotal roles in the pathogenesis of OA. In this process, the mitochondria are the major source of ROS production in cells, suggesting a role of mitochondrial dysfunction in this type of arthritis. This may also be promoted by inflammatory cytokines such as IL-1beta and TNF alpha which contribute to chondrocyte death. In patients with OA, the expression of endoplasmic reticulum (ER) stress-associated molecules is positively correlated with cartilage degeneration. Melatonin and its metabolites are broad spectrum antioxidants and free radical scavengers which regulate a variety of molecular pathways such as inflammation, proliferation, apoptosis, and metastasis in different pathophysiological situations. Herein, we review the effects of melatonin on OA, focusing on its ability to regulate apoptotic processes and ER and mitochondrial activity. We also evaluate likely protective effects of melatonin on OA pathogenesis. PMID- 27555372 TI - Challenges for teens with sickle cell disease extend to mental health. PMID- 27555373 TI - Evaluation of oral microbiota in undernourished and eutrophic children using checkerboard DNA-DNA hybridization. AB - The aim of this study was to evaluate the relationship among nutritional status, gingival health and the composition of oral microbiota in children of a public school from a very poor area of San Miguel de Tucuman. Forty-five children ranging in age from 6 to 14 years old, 13 males and 32 females were studied. Twenty of these children were undernourished (Lejarraga-Morasso Table) and twenty five were eutrophic. A clinical study that included DMF and dmf indexes, Loe Silness Plaque Index and bleeding on probing was performed. For microbiological study, saliva samples without stimulation were taken; aliquots of them were immediately placed in TAE buffer pH 7.6, adding NaOH (N and keeping at -70 degrees C until processed by checkerboard DNA-DNA hybridization method to check the presence of 40 oral microorganism species. Positive bleeding on probing was present in more than 80% of children, without significant differences between eutrophic and undernourished groups. Same result were obtain for the other clinical indexes (p > 0.05, Two Way ANOVA). Significant differences were found for some oral microorganism species, with a higher percentage of undernourished children harboring them. That was the case of S. gordonii (p < 0.05), Capnocitophaga gingivalis and C. ochraceae (p < 0.01 and p < 0.10, respectively), F. nucleatum ss nucleatum (p < 0.05), P. nigrescens (p < 0.10), Campylobacter gracilis (p < 0,05), and T. denticola (p < 0.10, multiple logistic regression). Significant differences were also found between children groups for E. saborreum (p < 0.001), P. acnes (p < 0.10), G. morbillorum (p < 0.05) and L. buccalis (p < 0.10). Gingivitis and bleeding on probing would not be related to nutritional status in the groups of children studied. There were significant differences for the presence of some of the main periodontal pathogen species between eutrophic and undernourished children. It would be important to study the meaning of significant differences found for the other microorganisms more deeply. PMID- 27555374 TI - Prevention of bisphosphonate-related osteonecrosis of the jaws in patients with prostate cancer treated with zoledronic acid - A prospective study over 6 years. AB - INTRODUCTION: To explore the preventive effect of a prophylactic oral and maxillofacial treatment to reduce bisphosphonate associated necrosis of the jaws (BRONJ) in metastatic prostate cancer (PC) patients treated with zoledronic acid (4.0 mg i.v./months). MATERIALS AND METHOD: 253 PC patients with bone metastases were prospectively randomized. All patients received baseline assessments including a dental panoramic tomogram. Group A was monitored and treated where deemed necessary by the patient's dentist and were re-evaluated once a year. In group B patients were monitored and treated where necessary by the authors at 12 week intervals. We compared the incidence rate per year (IR) and incidence proportion (IP) in both cohorts and assessed independent risk factors for BRONJ. RESULTS: Patients in group A were evaluated 3.2 (range 2-4) vs. 6.8 times (range 4-24) in group B. A significantly higher proportion of dental extractions was performed in group B vs. A (26.7% vs. 22.7%, p = 0.006). A BRONJ was detected with an IP of 23.3% vs. 2.2% in group A vs. B, revealing a 2.59 fold higher relative risk for group A (p = 0.01, 95% CI 0.01-0.56). The IR in group A was 0.073 cases/year while the IR in group B was significantly decreased by 82% to 0.0131 (p < 0.001). Extraction therapy was the only independent risk factor for BRONJ (p < 0.0001; 95% CI 21.22-189.06). CONCLUSIONS: Preventive oral and maxillofacial treatment before bisphosphonate application combined with 3-monthly dental follow-ups significantly reduces the occurrence and risk of BRONJ in PC patients. Therefore this approach should be implemented in the specific treatment algorithms. PMID- 27555375 TI - A new approach to nasoseptal fractures: Submucosal endoscopically assisted septoplasty and closed nasal reduction. AB - BACKGROUND: Nasal bone fracture is the most common among facial bone fractures. The prevalence of concomitant septal and nasal bone fractures fluctuates between 34% and 96.2%. An adequate management of such fractures is essential to prevent complications such as post-traumatic nasal obstruction and nasoseptal deformities. The purpose of the present study is to introduce the submucosal endoscopically assisted septoplasty (SEAS) as an alternative approach for acute septal lesions and to report our experience and outcomes. METHODS: Retrospective review including patients with nasal fracture in association with septal fracture (nasoseptal fractures) who underwent to submucosal endoscopically assisted septoplasty and closed nasal reduction. The surgical technique is described and a video is presented. RESULTS: Ninety patients were included; 23% were female and 77% were male, with a mean age of 40 years. All the cases were workplace accidents or commuting accidents. The mean time elapsed between the accident and surgery was 15 days. There were no technique-related intraoperative complications. Three (3.3%) patients suffered a subsequent nasal obstruction and/or deviation of the nasal axis, requiring subsequent secondary open rhinoseptoplasty. CONCLUSIONS: Submucosal endoscopically assisted septoplasty and closed nasal reduction for the treatment of nasoseptal fractures is a novel approach that reduces the rate of secondary rhinoseptoplasty as compared to other authors' reports. The technique described is reproducible, cost-effective and has very encouraging outcomes. LEVEL OF EVIDENCE: IV Therapeutic. PMID- 27555376 TI - Toxic effects of copper sulfate and copper nanoparticles on minerals, enzymes, thyroid hormones and protein fractions of plasma and histopathology in common carp Cyprinus carpio. AB - Differences in toxicological effects of dissolved copper and copper nanoparticles were studied in common carp, Cyprinus carpio. The fish were exposed to 0.25mgL-1 copper as copper sulfate (0.25Cu), 0.25mgL-1 copper as copper oxide nanoparticles (0.25NCu) and 25mgL-1 copper as copper oxide nanoparticles (25NCu) over 14days. Plasma biochemical, enzymatic and hormonal characteristics, and liver and kidney histopathology were examined at the end of the experiment. The results showed that both forms of copper had no significant effects on plasma calcium levels, however, significantly increased plasma phosphorous levels, compared to control group (no added copper). Plasma alanine transaminase (ALT) activity increased in 0.25Cu and 25NCu treatments compared to the control and 0.25NCu treatments. Nanoparticle copper exposure significantly decreased plasma alkaline phosphatase (ALP) activity compared to the control and 0.25Cu treatments. Only copper sulfate exposure caused plasma aspartate transaminase (AST) elevation. Both copper forms increased plasma T4 and free T4 (FT4); however, copper sulfate effect was higher than nanoparticle copper. Copper sulfate exposure increased plasma albumin fraction, whereas, 25mgL-1 copper nanoparticle exposure increased plasma alpha2 globulin fraction compared to the control. Both copper forms damaged the fish liver and kidney, however, copper sulfate caused more severe damages compared to nanoparticle copper. Overall, except for plasma ALP and alpha2-globulin fraction, dissolved copper seems to be more toxic than nanoparticle copper in common carp. PMID- 27555377 TI - Minocycline, a putative neuroprotectant, co-administered with doxorubicin cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer. AB - Minocycline is purported to have neuroprotective properties in experimental models of some human neurologic diseases, and has therefore been identified as a putative neuroprotectant for chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. However, because its mechanism of action is believed to be mediated through anti-inflammatory, anti-apoptotic, and anti-oxidant pathways, co-administration of minocycline with chemotherapeutic agents has the potential to reduce the efficacy of anticancer drugs. The objective of this study is to evaluate the effect of minocycline on the activity of the AC chemotherapeutic regimen (Adriamycin [doxorubicin], Cytoxan [cyclophosphamide]) in in vitro and in vivo models of triple-negative breast cancer (TNBC). Clonogenic and methylthiazol tetrazolium (MTT) assays were used to assess survival and viability in two TNBC cell lines treated with increasing concentrations of AC in the presence or absence of minocycline. Biomarkers of apoptosis, cell stress, and DNA damage were evaluated by western blot. The in vivo effects of AC and minocycline, each alone and in combination, were assessed in a xenograft model of TNBC in female athymic nude mice by weekly tumor volume measurement, body and organ weight measurement, and histopathology. Apoptosis and proliferation were characterized by immunohistochemistry in the xenografts tumors. Brains from tumor-bearing mice were evaluated for microglial activation, glial scars, and the proportion of neural progenitor cells. Data from these in vitro and in vivo studies demonstrate that minocycline does not diminish the cytotoxic and tumor-suppressive effects of this chemotherapeutic drug combination in TNBC cells. Moreover, minocycline appeared to prevent the reduction in doublecortin-positive neural progenitor cells observed in AC-treated mice. We posit that minocycline may be useful clinically for its reported neuroprotective activity in breast cancer patients receiving AC without loss of chemotherapeutic efficacy. PMID- 27555378 TI - Interactions between phasic alerting and consciousness in the fronto-striatal network. AB - Only a small fraction of all the information reaching our senses can be the object of conscious report or voluntary action. Although some models propose that different attentional states (top-down amplification and vigilance) are necessary for conscious perception, few studies have explored how the brain activations associated with different attentional systems (such as top-down orienting and phasic alerting) lead to conscious perception of subsequent visual stimulation. The aim of the present study was to investigate the neural mechanisms associated with endogenous spatial attention and phasic alertness, and their interaction with the conscious perception of near-threshold stimuli. The only region demonstrating a neural interaction between endogenous attention and conscious perception was the thalamus, while a larger network of cortical and subcortical brain activations, typically associated with phasic alerting, was highly correlated with participants' conscious reports. Activation of the anterior cingulate cortex, supplementary motor area, frontal eye fields, thalamus, and caudate nucleus was related to perceptual consciousness. These data suggest that not all attentional systems are equally effective in enhancing conscious perception, highlighting the importance of thalamo-cortical circuits on the interactions between alerting and consciousness. PMID- 27555379 TI - Genetic Contributions of Inflammation to Depression. AB - This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case-control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1beta, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2. Moreover, increased blood cytokines mRNA expression (especially of IL-1beta) identifies patients that are less likely to respond to conventional antidepressants. However, even for the most replicated findings there are inconsistent results, not only between studies, but also between the immune effects of the genetic variants and the resulting effects on depression. We find evidence that these discrepant findings may be explained, at least in part, by the heterogeneity of the depression immunophenotype, by environmental influences and gene * environment interactions, and by the complex interfacing of genetic variants with gene expression. Indeed, some of the most robust findings have been obtained in patients developing depression in the context of treatment with interferon-alpha, a widely used model to mimic depression in the context of inflammation. Further 'omics' approaches, through GWAS and transcriptomics, will finally shed light on the interaction between immune genes, their expression, and the influence of the environment, in the pathogenesis of depression. PMID- 27555380 TI - Dynamic Alterations of Rat Nucleus Accumbens Dendritic Spines over 2 Months of Abstinence from Extended-Access Cocaine Self-Administration. AB - Chronic cocaine exposure influences the density and morphology of dendritic spines on medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a critical brain region for cocaine craving. However, the relationship between spine plasticity and craving remains unclear. To study this relationship, we trained rats to self-administer cocaine using an extended-access regimen (6 h per day, 10 days); controls self-administered saline. Previously, a time-dependent intensification (incubation) of cue-induced cocaine craving has been demonstrated after withdrawal from this regimen; furthermore, Ca2+-permeable AMPA receptors (CP-AMPARs) increase in the NAc core after ~1 month of withdrawal and thereafter mediate the expression of incubated craving. Although neither craving nor CP AMPAR levels were measured in the present study, we killed rats at four withdrawal day (WD) time-points (WD14, WD25, WD36, or WD60) selected to span the rising phase of incubation and the transition from low to high CP-AMPAR levels. MSNs were iontophoretically filled with Lucifer yellow and spines were analyzed with NeuronStudio software. Compared with saline controls, cocaine rats showed no changes in spine density or morphology in the NAc core on WD14 or WD25. On WD36, approximately the withdrawal time when stable elevation of CP-AMPAR levels is detected, the cocaine group exhibited increased density of thin spines in the NAc core. By WD60, however, this effect had reversed: the density of thin spines was lower in cocaine rats compared with saline rats. In contrast, craving and CP AMPAR levels remain high on WD60. We also assessed spine density on WD36 in the dorsolateral striatum, a region that is not implicated in incubation of cocaine craving and does not undergo CP-AMPAR plasticity. Here, the cocaine group exhibited a small leftward shift in the distribution of spine densities plotted as a cumulative distribution, opposite to the effect found in the NAc core. Overall, our results demonstrate changes in NAc core spines over 2 months of withdrawal but no simple relationship between the time dependency of these spine changes and the previously demonstrated time course of incubation of cocaine craving. However, they raise the possibility that CP-AMPAR accumulation in the NAc core occurs in a population of thin spines that emerges after ~1 month of withdrawal. PMID- 27555381 TI - Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults. AB - In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation. PMID- 27555383 TI - Investigating the spatial distribution of growth anomalies affecting Montipora capitata corals in a 3-dimensional framework. AB - Diseases have caused significant reductions in coral populations throughout the global ocean. Despite a substantial effort to thoroughly characterize the epizootiology and etiology of coral diseases, little is known about the distribution and spatial clustering of disease lesions on affected coral colonies. This study investigated spatial clustering of the coral disease, growth anomaly (GA), which exhibits high levels of prevalence and severity in Montipora capitata and other corals at Wai'opae, southeast Hawai'i Island. Like many other coral diseases, the patterns of disease spread and transmissibility of GA remains unknown. We utilized cutting-edge 3D reconstruction techniques to map the precise spatial distribution of GAs on affected coral colonies. Three statistical measures, Ripley's K, Moran's I, and the Kolmogorov-Smirnov test were used to determine if the GA lesions were distributed in a non-random pattern. Each measure showed the GA lesions exhibited distinct spatial clustering on all ten affected colonies analyzed in this study. Our study is not only the first 3D analysis of intra-colony disease clustering, but also provides a novel approach for investigating and quantifying levels of disease clustering in order to improve our understanding of coral disease epizootiology, transmission, and etiology. PMID- 27555384 TI - Intramolecular trans-Dicarbofunctionalization of Alkynes by a Formal anti Carbopalladation/Stille Cascade. AB - An intramolecular Pd-catalyzed trans-dicarbofunctionalization of internal alkynes using aryl bromides and aryl stannanes is presented. Tetrasubstituted double bonds embedded in an oligocyclic ring system are obtained in a regio- and diastereoselective fashion. The transformation features a broad substrate scope and functional-group tolerance. PMID- 27555423 TI - Longitudinal diffusion tensor imaging of the rat brain after hexachlorophene exposure. AB - Longitudinal MRI employing diffusion tensor imaging and T2 mapping approaches has been applied to investigate the mechanisms of white matter damage caused by acute hexachlorophene neurotoxicity in rats in vivo. Male Sprague-Dawley rats were administered hexachlorophene orally once a day for five consecutive days at a dose of 30mg/kg and were monitored in 7T MRI scanner at days 0 (baseline), 3, 6, 13, and 20 following the first hexachlorophene dose. Quantitative T2 maps as well as a number of diffusion tensor parameters (fractional anisotropy, radial and axial diffusivity, apparent diffusion coefficient, and trace) were calculated from corresponding MR images. T2, as well as all diffusion tensor derived parameters (except fractional anisotropy) showed significant changes during the course of neurotoxicity development. These changes peaked at 6days after the first dose of hexachlorophene (one day after the last dose) and recovered to practically baseline levels at the end of observation (20days from the first dose). While such changes in diffusivity and T2 relaxation clearly demonstrate myelin perturbations consistent with edema, the lack of changes of fractional anisotropy suggests that the structure of the myelin sheath was not disrupted significantly by hexachlorophene in this study. This is also confirmed by the rapid recovery of all observed MRI parameters after cessation of hexachlorophene exposure. PMID- 27555424 TI - Water Formation for the Metalation of Porphyrin Molecules on Oxidized Cu(111). AB - Herein the formation of water molecules in the intermediate step of the redox reaction of porphyrins self-metalation on O/Cu(111) is demonstrated. Photoemission measurements show that the temperature on which porphyrins pick-up a substrate metal atom on O/Cu(111) is reduced by about 185+/-15 K with respect to the pure Cu(111). DFT calculations clearly indicate that the formation of a water molecule is less expensive than the formation of H2 on the O/Cu(111) substrate and, in some cases, it can be also exothermic. PMID- 27555425 TI - Non-fatal impalement of the brain: A case report. AB - We present a rare case of a non-fatal impalement injury of the brain. A 13-year old boy was found in his classroom unconsciously lying on floor. His classmates reported that they had been playing, and throwing building bricks, when suddenly the boy collapsed. The emergency physician did not find significant injuries. Upon admission to a hospital, CT imaging revealed a "blood path" through the brain. After clinical forensic examination, an impalement injury was diagnosed, with the entry wound just below the left eyebrow. Eventually, the police presented a variety of pointers that were suspected to have caused the injury. Forensic trace analysis revealed human blood on one of the pointers, and subsequent STR analysis linked the blood to the injured boy. Confronted with the results of the forensic examination, the classmates admitted that they had been playing "sword fights" using the pointers, and that the boy had been hit during the game. The case illustrates the difficulties of diagnosing impalement injuries, and identifying the exact cause of the injury. PMID- 27555382 TI - Therapeutic Implications of Brain-Immune Interactions: Treatment in Translation. AB - A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specific behaviors. What is clear is that the impact of inflammation on the brain cuts across psychiatric disorders and engages dopaminergic and glutamatergic pathways that regulate motivation and motor activity as well as the sensitivity to threat. Given the ability to identify patient populations with increased inflammation, the precision of interventions can be further tuned, in conjunction with the ability to establish target engagement in the brain through the use of multiple neuroimaging strategies. After a brief overview of the mechanisms by which inflammation affects the brain and behavior, this review examines the extant literature on the efficacy of anti inflammatory treatments, while forging guidelines for future intelligent clinical trial design. An examination of the most promising therapeutic strategies is also provided, along with some of the most exciting clinical trials that are currently being planned or underway. PMID- 27555426 TI - Perceived Injustice Is Associated With Pain and Functional Outcomes in Children and Adolescents With Chronic Pain: A Preliminary Examination. AB - : Chronic pain is prevalent in children/adolescents and contributes to high rates of healthcare utilization. Research suggests injustice perceptions about pain are important in adult patients and a possible treatment focus. We conducted a preliminary evaluation of the psychometric properties of the Injustice Experiences Questionnaire (IEQ) and the relationship between injustice perceptions, pain, and functioning in chronic pain patients (N = 139, mean age = 15 years, 72% female) presenting to a pediatric pain clinic. Patients completed measures assessing pain intensity, injustice perceptions about pain, catastrophizing, overall functional disability, emotional functioning, social functioning, and school functioning. The IEQ showed good reliability and validity. Higher levels of perceived injustice were associated with higher levels of pain intensity, catastrophizing, and functional disability, and with poorer emotional, social, and school functioning. Additionally, perceived injustice remained significantly associated with pain intensity, functional disability, emotional functioning, social functioning, and school functioning after accounting for relevant demographic and clinical factors. This is the first study to suggest that injustice perceptions are important in the experience of pediatric chronic pain patients. Future studies should more thoroughly examine the psychometric properties of the IEQ in children/adolescents and elucidate the causal nature of these relationships, which will inform treatment efforts to improve pediatric pain care. PERSPECTIVE: This initial investigation suggests that injustice perceptions about pain can be reliably and validly measured and are tied to important clinical outcomes in children/adolescents. Future studies that replicate and extend these preliminary results are necessary to determine the extent to which injustice perceptions are an important target for intervention. PMID- 27555428 TI - The Effect of Perceived Injustice on Appraisals of Physical Activity: An Examination of the Mediating Role of Attention Bias to Pain in a Chronic Low Back Pain Sample. AB - : The current study examined the relationship between perceived injustice and attentional bias (AB) toward pain among individuals with chronic low back pain asked to perform and appraise the pain and difficulty of a standardized set of common physical activities. A pictorial dot-probe task assessed AB toward pain stimuli (ie, pain faces cueing pain), after which participants performed the physical tasks. Participants also rated face stimuli in terms of pain, sadness, and anger expression. As hypothesized, perceived injustice was positively associated with AB toward pain stimuli; additionally, perceived injustice and AB were positively associated with appraisals of pain and difficulty. Counter to expectations, AB did not mediate the relationship between perceived injustice and task appraisals, suggesting that AB is insufficient to explain this relationship. Exploratory analyses indicated that participants with higher levels of perceived injustice rated stimulus faces as sadder and angrier; no such differences emerged for pain ratings. To our knowledge, this is the first study to examine the association between perceived injustice and AB toward pain, as well as perceived injustice and in vivo appraisals of common physical activity. Results extend existing literature and suggest that attentional and potential interpretive bias should be considered in future research. PERSPECTIVE: This article identifies significant associations between perceived injustice, biased attention to pain, and appraisals of common physical activities among individuals with chronic low back pain. These findings suggest targets for intervention as well as directions for future research regarding individuals with high perceptions of injustice related to pain. PMID- 27555427 TI - Disease-Related, Nondisease-Related, and Situational Catastrophizing in Sickle Cell Disease and Its Relationship With Pain. AB - : Catastrophizing is a potent psychological modulator of pain across several chronic pain populations; yet despite evidence that patients with sickle cell disease (SCD) catastrophize more than patients with other chronic pain conditions, previous research indicates that catastrophizing is not related to sickle cell pain after controlling for relevant covariates such as depression. Recent research suggests that pain-related catastrophizing should be assessed across pain contexts (eg, dispositional and situational). In this study, we measured disease-specific, general non-disease-related, and situational catastrophizing and assessed the relationship between these contextual dimensions of catastrophizing and laboratory and clinical pain among patients with SCD. Results revealed differential catastrophizing across pain contexts, with patients reporting greater catastrophizing about SCD-specific pain compared with non-SCD pain and laboratory pain. SCD-specific and non-SCD catastrophizing were associated with clinical pain outcomes, and situational catastrophizing with markers of central sensitization and laboratory pain. Further examination of the time course of laboratory responses revealed that increases in situational catastrophizing were associated with subsequent increases in laboratory pain sensitivity. Taken together, results show the relevance of catastrophizing in understanding pain in SCD, and suggest that context-specific anchors may be beneficial in predicting different aspects of the pain experience (eg, chronic pain, pain sensitization). PERSPECTIVE: Patients with SCD report greater catastrophizing about sickle cell-specific pain relative to other pains. Disease specific and non-disease-related pain catastrophizing were associated with clinical pain, and situational catastrophizing predictive of subsequent laboratory pain. Evaluation of context-specific catastrophizing may more accurately predict different aspects of the pain experience. PMID- 27555429 TI - Participant Preferences for Pharmacologic Chronic Pain Treatment Trial Characteristics: An ACTTION Adaptive Choice-Based Conjoint Study. AB - : Barriers to clinical trial recruitment can delay study completion, potentially resulting in increased costs and an unrepresentative sample. In the current study of 150 participants with chronic pain, we used a computerized adaptive choice based conjoint survey that included 8 characteristics that may affect enrollment in pharmacologic pain treatment trials (ie, treatment allocation, frequency of pain ratings, treatment administration method, current medications, number of study visits, availability of evening and weekend visits, invasiveness of laboratory procedures, payment). These data were analyzed using Sawtooth Software ver. 8.4.8 (Sawtooth Software, Inc, Orem, UT), which identifies the characteristics that dominate participants' decisions across multiple sets of potential trials. Three characteristics had the largest relative importance in participants' trial preferences: 1) invasiveness of required laboratory procedures (ie, 22%), with no procedures or blood tests preferred over ice-water sensory testing or skin biopsy; 2) ability to continue current pain medications (21%); and 3) payment for study participation (21%), with higher payment preferred. The fourth most important characteristic was number of study visits (13%), with participants preferring fewer in-person visits and more phone contacts. Understanding the preferences of potential participants is an important step toward enhancing enrollment in pain treatment trials. PERSPECTIVE: This article presents the preferences of individuals with chronic pain conditions regarding modifiable pain treatment trial characteristics (eg, number of study visits, payment, treatment allocation). These findings may help to improve enrollment into analgesic clinical trials and in turn accelerate the development of new pain treatments. PMID- 27555430 TI - Endovascular Aneurysm Sealing: Early and Midterm Results From the EVAS FORWARD Global Registry. AB - PURPOSE: To report the early and 12-month results of a global registry of patients treated with endovascular aneurysm sealing (EVAS) for abdominal aortic aneurysms (AAAs). METHODS: The EVAS FORWARD Global Registry was a postmarket, multicenter, open-label, single-arm registry that enrolled 277 patients (mean age 75 years; 228 men) treated with the Nellix EVAS system for nonruptured AAAs at 18 sites over a 1-year period. The cohort had challenging aortic anatomy, with 17% having a proximal aortic neck length <10 mm, 8% a neck angulation >60 degrees , and 20% an iliac diameter >25 mm. Baseline and follow-up computed tomography images were assessed by an independent core laboratory, and major adverse events were reviewed by an independent safety committee. RESULTS: Three patients died within 30 days of the procedure (none device-related). There were 13 endoleaks recorded in this time frame: 8 type Ia, 1 type Ib, and 5 type II. Root cause analysis demonstrated that the majority of type Ia endoleaks were due to technical error (low device placement and underfilling of the endobags). Between 30 days and 1 year, there were 4 new type Ia endoleaks; all were treated. There was also 1 type III endoleak between a Nellix device and a distal extension limb. At 1 year, the persistent endoleak rate was 0.7% (1 type Ia and 1 type II). The Kaplan-Meier estimates of freedom from types I and II endoleak at 12-month follow up were 96% and 98%, respectively. The estimate of freedom from open conversion (n=7) was 98% at 12 months and the rate of freedom from any reintervention was 92%. The need for secondary intervention was associated with aortic morphology; for patients meeting the requirements of the instructions for use (IFU), the freedom from reintervention at 12 months was 98% compared with 86% when the implant was outside the IFU (p=0.009). At 1 year, the estimates of freedom from aortic-related and all-cause mortality were 98% and 95%, respectively. CONCLUSION: The EVAS FORWARD Global Registry documents the 12-month outcome of EVAS in an unselected group of patients with challenging aortic morphology. The results at present appear acceptable with regard to perioperative outcomes and complications. The type II endoleak rate is low. The place of EVAS in the armamentarium of techniques to treat AAAs will be defined by durability data in the longer term. PMID- 27555431 TI - Seduction and Its Impact on Instructions for Use. PMID- 27555432 TI - Lymph node staging in prostate cancer: perspective for the pathologist. AB - Pelvic lymph node dissection (PLND) currently represents the gold standard method for nodal staging in the setting of localised prostate cancer and may also have a therapeutic benefit in certain patients. The histopathological evaluation of PLND specimens plays a critical role in accurate lymph node staging, however there is currently a lack of consensus regarding the optimum approach and no quality parameters are in place. In addition, there are no guidelines as to the handling of less commonly encountered nodal specimens such as those identified within the anterior fat pad. This summary provides an overview of pertinent issues regarding lymph node staging in prostate cancer, with a focus on the histopathological evaluation of resected nodal specimens. We hope that this review will further the discussion on how to achieve a more standardised approach to the processing and reporting of PLND specimens in the setting of prostate cancer. PMID- 27555433 TI - Dysfibrinogenemia-associated novel heterozygous mutation, Shanghai (FGA c.169_180+2 del), leads to N-terminal truncation of fibrinogen Aalpha chain and impairs fibrin polymerization. AB - AIMS: A novel heterozygous variant, FGA c.169_180+2 del (designated fibrinogen Shanghai), was identified in a patient with dysfibrinogenemia with antiphospholipid antibody syndrome (APS) and recurrent venous thrombosis, and in his asymptomatic father. We aimed to reveal the functional implication of structural change caused by this variant. METHODS: Transcription analysis was performed with FGA minigene transfection assay to evaluate the impact of nucleosides deletion on mRNA editing. The fibrinogen isolated from propositus' plasma was used to characterise its functional defects. Fibrin polymerization and clot lysis experiments were performed by optical measurement of turbidity. Thrombin-catalysed fibrinopeptide release was analysed by the reversed-phase, high-performance liquid chromatography. The ultrastructures of fibrin clots were visualised by scanning electron microscopy. RESULTS: FGA c.169_180+2 del led to an aberrant mRNA with exon 2 skipping and encoded an shortened Aalpha chain with 42 amino acids truncation at its N-terminal. The propositus' fibrinogen had an impaired release of fibrinopeptide A and abnormal polymerization with a significantly prolonged lag time, a slower maximum slope and reduced final turbidity. The fibrin clot formed with propositus' fibrinogen showed thicker fibres with looser network structure. Clot lysis was normal using the purified fibrinogen but was significantly impaired using the plasma sample from propositus, compared with that from his father. CONCLUSIONS: Fibrinogen Shanghai results in N-terminal truncation of Aalpha chain, which does not interfere with synthesis, assembly or secretion of fibrinogen, but compromises fibrin polymerization and clot formation. APS at least partially contributes to the development of thrombosis in the propositus. PMID- 27555434 TI - Involvement of oxidative stress in increased peripheral nerve firing during spontaneous dysesthesia in a mouse model of ischemia-reperfusion. AB - Transient ischemia-reperfusion in the hand and foot elicits spontaneous dysesthesia. However, the mechanisms by which this occurs are not completely understood. The objectives of this study were to examine peripheral neural activity related to spontaneous dysesthesia in a mouse model of hind-paw transient ischemic-reperfusion and to investigate the involvement of oxidative stress in this neural activity. The femoral artery and vein were interrupted for 10min using tourniquet pressure, before the tourniquet was removed to allow reperfusion of the hind paw. Neural activity in the saphenous nerve was recorded during both ischemia and reperfusion. In both the ischemic phase and the reperfusion phase, the frequency of saphenous nerve firing was significantly increased compared to baseline. The antioxidant agent N-acetyl-l-cysteine inhibited significantly the firing of the saphenous nerve in both the maximum and minimum activity periods during ischemia, and in the maximum activity state after reperfusion percentage inhibition being approximately 68%, 60%, and 58%, respectively. In the reperfusion phase, the production of 4-hydroxy-2-noneal, a major product of endogenous lipid peroxidation, was significantly increased in the plantar skin, and this was inhibited by N-acetyl-l-cysteine. In the ischemic phase, a similar trend was observed. These results suggest that an increase in peripheral nerve activity related to oxidative stress may be involved in the spontaneous dysesthesia induced by transient ischemia-reperfusion. PMID- 27555435 TI - High degree of clonal reproduction and lack of large-scale geographic patterning mark the introduced range of the invasive vine, kudzu (Pueraria montana var. lobata), in North America. AB - PREMISE OF THE STUDY: Pueraria montana var. lobata, or kudzu, is an invasive species whose invasion in North America is not genetically well characterized. The clonality of kudzu introduces challenges to population genetic analyses that can bias the assessment of spatial patterns of genotypes. Assessing patterns of genetic diversity while considering clonality is necessary to understand the invasion and spread of kudzu in its invasive range. METHODS: We screened 1747 individuals from 87 populations across the invasive range with 15 microsatellite markers and a 789 bp chloroplast region. We performed detailed clonal analyses and tested levels of genetic diversity, population structure, and phylogeographic relationships. KEY RESULTS: Kudzu exhibited a clonal rate of 80%, and was more heterozygous than other long-lived perennials. We detected only 353 distinct clonal lineages, with over 60% sharing a maternal haplotype. Populations were established with few genotypes, many consisting of only a single clone. We found no isolation by distance. Despite high genetic diversity, we found little geographic patterning. CONCLUSIONS: Kudzu is highly clonal with few genetically distinct lineages and haplotypes existing in the introduced range. Our data are consistent with a large single introduction, or a few at most. Introduced lineages are geographically randomly distributed but isolated, suggesting that genotypes rarely expand into already established populations. No route of expansion was detectable from an original introduction. The invasion of kudzu does not seem to have been dominated by a single genotype, thus standing genetic variation and phenotypic plasticity are more likely mechanisms explaining kudzu's invasion success. PMID- 27555436 TI - Frequent colonization and little in situ speciation in Senecio in the tropical alpine-like islands of eastern Africa. AB - PREMISE OF THE STUDY: Floras of continental habitat islands, like those of islands, originate mostly through colonization, which can be followed by in situ speciation. We here address the question of the relative importance of colonization and in situ diversification in the high-altitude areas of the eastern African high mountains, the tropical Afroalpine Region, using the most species-rich genus in the region, Senecio, as an example. METHODS: We expanded earlier Senecioneae phylogenies by adding more tropical African species and analyzed our phylogenetic tree biogeographically. KEY RESULTS: Senecio contains at least five clades with tropical African species, all of them containing tropical afroalpine species. Between four to 14 independent colonization events into the tropical Afroalpine most likely from montane regions in southern Africa were found. Additionally, relationships of tropical afroalpine species to Palearctic and South American taxa were identified. Although some in situ diversification occurred in Senecio in the tropical Afroalpine, the resulting number of species per clade is never higher than seven. CONCLUSION: Like other genera, Senecio colonized the tropical Afroalpine several times independently. Comparison with Mt. Kinabalu, a small tropical alpine-like region in Southeast Asia, and alpine-like regions in the Andes implies that rates of in situ speciation might be linked to area size. PMID- 27555437 TI - Specialization in the yucca-yucca moth obligate pollination mutualism: A role for antagonism? AB - PREMISE OF THE STUDY: Specialized brood pollination systems involve both mutualism and antagonism in the overall interaction and have led to diversification in both plants and insects. Although largely known for mutualism, the role of the antagonistic side of the interaction in these systems has been overlooked. Specialization may be driven by plant defenses to feeding by the insect larvae that consume and kill developing plant ovules. The interaction among yuccas and yucca moths is cited as a classic example of the importance of mutualism in specialization and diversification. Pollinators moths are very host specific, but whether this specificity is due to adult pollination ability or larval feeding ability is unclear. Here, I test the potential role of antagonism in driving specialization among yuccas and yucca moths. METHODS: I examined the ability of the most-polyphagous yucca moth pollinator, Tegeticula yuccasella, to pollinate and develop on five Yucca species used across its range. Yucca species endemic to the Great Plains and Texas were transplanted to a common garden in Syracuse, New York and exposed to the local pollinator moth population over 3 years. KEY RESULTS: Local moths visited all but one of the Yucca species, but had drastically lower rates of successful larval development on non-natal Yucca species in comparison to the local host species. CONCLUSION: Specialization in many brood pollination systems may be strongly influenced by the antagonistic rather than the mutualistic side of the overall interaction, suggesting that antagonistic coevolution is a possible source of diversification. PMID- 27555438 TI - Flower-like ZnO decorated polyaniline/reduced graphene oxide nanocomposites for simultaneous determination of dopamine and uric acid. AB - A novel sensor was fabricated by electrochemical deposition of ZnO flower like/polyaniline nanofiber/reduced graphene oxide nanocomposite (ZnO/PANI/RGO) on glassy carbon electrode (GCE) for direct detection of dopamine (DA) and uric acid (UA) in the presence of fixed concentration of ascorbic acid (AA). Surface morphology and characterization of the modified electrodes were confirmed by field emission scanning microscopy (FE-SEM), X-ray diffraction (XRD), Raman and FT-IR spectroscopies. For individual detection, the linear responses were in the two concentration ranges of 0.001-1 MUM and 1-1000 MUM with detection limit 0.8 nM (S/N = 3) for DA, and also 0.1-100 MUM and 100-1000 MUM with detection limit 0.042 MUM (S/N = 3) for UA. Simultaneous determination of these species in their mixture solution showed the linear responses in the two concentration ranges of 0.1-90 MUM and 90-1000 MUM with detection limit 0.017 MUM (S/N = 3) for DA and also showed two linear range of 0.5-90 MUM and 100-1000 MUM with detection limit 0.12 MUM (S/N = 3) for UA, with coexistence of 1000 MUM AA. The applicability of sensor for the analysis of DA, and UA in dopamine injection solution, human serum and human urine samples was successfully demonstrated. PMID- 27555439 TI - A polystyrene binding target-unrelated peptide isolated in the screening of phage display library. AB - Phage display is a powerful methodology for the identification of peptide ligands binding to any desired target. However, the selection of target-unrelated peptides (TUPs) appears as a huge problem in the screening of phage display libraries through biopanning. The phage-displayed peptide TLHPAAD has been isolated both in our laboratory and by another reserach group on completely different screening targets prompting us to hypothesize that it may be a potential TUP. In the current study, we analyzed the binding characteristics and propagation rate of phage clone displaying TLHPAAD peptide (SW-TUP clone). The results of ELISA experiment and phage recovery assay provided strong support for the notion that SW-TUP phage binds to polystyrene with a significantly higher affinity than control phage clones. Furthermore, this polystyrene binding was demonstrated to occur in a concentration- and pH-dependent mode. Characterization of the propagation profile of phage clones within a specified time course revealed no statistically significant difference between the amplification rate of SW-TUP and control phages. Our findings lead us to the conclusion that SW-TUP phage clone with the displayed peptide TLHPAAD is not a true target binder and its selection in biopanning experiments results from its bidning affinity to the polystyrene surface of the solid phase. PMID- 27555440 TI - Polydopamine assisted fabrication of titanium oxide nanoparticles modified column for proteins separation by capillary electrochromatography. AB - Development of a simple method for preparation of stable open tubular (OT) columns for proteins separation by capillary electrochromatography is still challenging. In this work, the titanium oxide (TiO2) nanoparticles coated OT column was successfully prepared for separation of proteins by capillary electrochromatography. The polydopamine (PDA) film was first formed in the inner surface of a fused-silica capillary by the self-polymerization of dopamine under alkaline conditions. Then the TiO2 coating was deposited onto the surface of pre modified capillary with PDA by a liquid phase deposition process. The plentifully active hydroxyl groups in PDA coating can chelate with Ti(4+) to boost the nucleation and growth of TiO2 film. The as-prepared TiO2 coated OT column was characterized by scanning electron microscopy and measurement of electroosmotic flow. Furthermore, the influence of liquid phase deposition time on the TiO2 coating was investigated. The TiO2 coated OT column was used for successful separation of two variants of beta-lactoglobulin and eight glycoisoforms of ovalbumin. The column demonstrated good repeatability and stability. The relative standard deviations of migration times of proteins representing run-to-run, day to-day, and column-to-column were less than 3.7%. Moreover, the application of the column was verified by successful separation of acidic proteins in egg white. PMID- 27555441 TI - Computational simulation analysis on human SOD1 mutant (H80R) exposes the structural destabilization and the deviation of Zn binding that directs familial amyotrophic lateral sclerosis. PMID- 27555442 TI - The CHEVI tethering complex: facilitating special deliveries. AB - VPS33B and VIPAR comprise the two known components of the recently christened class C Homologues in Endosome-Vesicle Interaction (CHEVI) complex, thought to act as a tethering complex in endosomal trafficking distinct from the HOPS and CORVET complexes in mammalian cells. A recent paper in The Journal of Pathology further explores the role of the CHEVI complex in the biogenesis of alpha granules in megakaryocytes, identifying two novel interactors of this complex: alpha-tubulin and SEC22B, and demonstrating that VPS33B expression is required for the localization of SEC22B and the alpha-granule cargo VWF to proplatelets in megakaryocytes. These findings advance the current knowledge of the function of the CHEVI complex in alpha-granule biogenesis and together with studies in other systems, corroborate its role in the specialized delivery of cargo in different cell types. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27555443 TI - Opinion: Science in the age of selfies. PMID- 27555445 TI - Monodisperse AIE-Active Conjugated Polymer Nanoparticles via Dispersion Polymerization Using Geminal Cross-Coupling of 1,1-Dibromoolefins. AB - Monodisperse AIE (aggregation-induced emission)-active conjugated polymer nanoparticles are synthesized by dispersion polymerization using geminal Suzuki cross-coupling of 1,1-dibromoolefins. The size of the nanoparticles can be adjusted by varying the concentration of the initial monomer. PMID- 27555446 TI - Multiscale approaches to crowd dynamics and the reliability of data from experiments: Comment on "Human behaviours in evacuation crowd dynamics: From modelling to "big data" toward crisis management" by Nicola Bellomo et al. PMID- 27555447 TI - Effects of foot orthoses with medial arch support and lateral wedge on knee adduction moment in patients with medial knee osteoarthritis. AB - BACKGROUND: There is contradictory evidence regarding whether the addition of medial arch supports to laterally wedged insoles reduces knee adduction moment, improves comfort, and reduces knee pain during the late stance phase of gait. OBJECTIVES: To verify if such effects occur in participants with medial knee osteoarthritis. STUDY DESIGN: Randomized single-blinded study. METHODS: Gait analysis was performed on 18 patients affected by medial knee osteoarthritis. Pain and comfort scores, frontal plane kinematics and kinetics of ankle, knee, and hip were compared in four conditions: without foot orthosis, with foot orthoses, with medial arch support, and with foot orthoses with medial arch support and lateral wedge insoles with 6 degrees and 10 degrees inclination. RESULTS: Lower-extremity gait kinetics were characterized by a significant decrease, greater than 6%, in second peak knee adduction moment in laterally wedged insole conditions compared to the other conditions ( p < 0.001; effect size = 0.6). No significant difference in knee adduction moment was observed between laterally wedged insole conditions. In contrast, a significant increase of 7% in knee adduction moment during the loading response was observed in the customized foot orthoses without lateral inclination condition ( p < 0.001; effect size = 0.3). No difference was found in comfort or pain ratings between conditions. CONCLUSION: Our study suggests that customized foot orthoses with a medial arch support may only be suitable for the management of medial knee osteoarthritis when a lateral wedge is included. Clinical relevance Our data suggest that customized foot orthoses with medial arch support and a lateral wedge reduce knee loading in patients with medial knee osteoarthritis (KOA). We also found evidence that medial arch support may increase knee loading, which could potentially be detrimental in KOA patients. PMID- 27555449 TI - 'Social' egg freezing and the UK's statutory storage time limits. AB - This article argues that the statutory time limits upon the storage of gametes have unintended and perhaps even perverse consequences for women freezing their eggs as insurance against age-related fertility decline. They work against good clinical practice and potentially represent an interference with a woman's right to respect for her family life, which is neither necessary nor proportionate. My claim will be that the statutory time limit, and the options for extension, are no longer fit for purpose. PMID- 27555448 TI - Temporal regulation of Lsp1 O-GlcNAcylation and phosphorylation during apoptosis of activated B cells. AB - Crosslinking of B-cell receptor (BCR) sets off an apoptosis programme, but the underlying pathways remain obscure. Here we decipher the molecular mechanisms bridging B-cell activation and apoptosis mediated by post-translational modification (PTM). We find that O-GlcNAcase inhibition enhances B-cell activation and apoptosis induced by BCR crosslinking. This proteome-scale analysis of the functional interplay between protein O-GlcNAcylation and phosphorylation in stimulated mouse primary B cells identifies 313 O GlcNAcylation-dependent phosphosites on 224 phosphoproteins. Among these phosphoproteins, temporal regulation of the O-GlcNAcylation and phosphorylation of lymphocyte-specific protein-1 (Lsp1) is a key switch that triggers apoptosis in activated B cells. O-GlcNAcylation at S209 of Lsp1 is a prerequisite for the recruitment of its kinase, PKC-beta1, to induce S243 phosphorylation, leading to ERK activation and downregulation of BCL-2 and BCL-xL. Thus, we demonstrate the critical PTM interplay of Lsp1 that transmits signals for initiating apoptosis after BCR ligation. PMID- 27555450 TI - Response to Editorial re 'Barriers to Transition in Young Adults with Neurogenic Bladder'. PMID- 27555451 TI - Wireless communication system via nanoscale plasmonic antennas. AB - Present on-chip optical communication technology uses near-infrared light, but visible wavelengths would allow system miniaturization and higher energy confinement. Towards this end, we report a nanoscale wireless communication system that operates at visible wavelengths via in-plane information transmission. Here, plasmonic antenna radiation mediates a three-step conversion process (surface plasmon -> photon -> surface plasmon) with in-plane efficiency (plasmon -> plasmon) of 38% for antenna separation 4lambda0 (with lambda0 the free-space excitation wavelength). Information transmission is demonstrated at bandwidths in the Hz and MHz ranges. This work opens the possibility of optical conveyance of information using plasmonic antennas for on-chip communication technology. PMID- 27555452 TI - Application of high resolution OCT to evaluate irregularity of Bowman's layer in asymmetric keratoconus. AB - Irregularity of the Bowman's layer (BL) in keratoconus (KC, sample size (n) = 28) and forme fruste keratoconus (FFKC, n = 18) eyes was evaluated. Subjects underwent high resolution OCT imaging (Bioptigen Inc., USA) and corneal tomography (Pentacam v1.20r41, OCULUS Optikgerate GmbH, Germany). Anterior edge of the BL was segmented. A Bowman's roughness index (BRI) was defined as the sum of the enclosed areas between segmented edge and a smooth 3rd order polynomial fit to the edge. BRI was compared with corneal aberrations, Keratoconus percentage index (KISA), Cone location magnitude index (CLMI) and Belin-Ambrosio enhanced ectasia display overall deviation index (BAD-D). Area under the curve (AUC) was determined with logistic regression (LR). Mean BRI (*10-3 ) was 2.12 mm2 , 1.81 mm2 and 1.7 mm2 in normal (n = 26), FFKC and KC eyes, respectively (p < 0.001). BAD-D (0.79) and BRI (0.74) had the best AUC for FFKC. By combining BAD D and BRI, the AUC improved to 0.85 (p = 0.01). For KC eyes, KISA (0.94), CLMI (0.88), BAD-D (0.96) and aberrations had comparable AUC (p > 0.05). However, LR with BRI and other indices didn't improve the AUC in KC eyes (p > 0.05). BRI was significantly reduced in FFKC and KC eyes. It improved the detection of FFKC but not KC eyes. PMID- 27555453 TI - The genetic basis of anoxygenic photosynthetic arsenite oxidation. AB - 'Photoarsenotrophy', the use of arsenite as an electron donor for anoxygenic photosynthesis, is thought to be an ancient form of phototrophy along with the photosynthetic oxidation of Fe(II), H2 S, H2 and NO2-. Photoarsenotrophy was recently identified from Paoha Island's (Mono Lake, CA) arsenic-rich hot springs. The genomes of several photoarsenotrophs revealed a gene cluster, arxB2AB1CD, where arxA is predicted to encode for the sole arsenite oxidase. The role of arxA in photosynthetic arsenite oxidation was confirmed by disrupting the gene in a representative photoarsenotrophic bacterium, resulting in the loss of light dependent arsenite oxidation. In situ evidence of active photoarsenotrophic microbes was supported by arxA mRNA detection for the first time, in red pigmented microbial mats within the hot springs of Paoha Island. This work expands on the genetics for photosynthesis coupled to new electron donors and elaborates on known mechanisms for arsenic metabolism, thereby highlighting the complexities of arsenic biogeochemical cycling. PMID- 27555454 TI - Pathways linking health literacy, health beliefs, and cognition to medication adherence in older adults with asthma. AB - BACKGROUND: Limited health literacy is associated with low adherence to asthma controller medications among older adults. OBJECTIVE: We sought to describe the causal pathway linking health literacy to medication adherence by modeling asthma illness and medication beliefs as mediators. METHODS: We recruited adults aged 60 years and older with asthma from hospital and community practices in New York, New York, and Chicago, Illinois. We measured health literacy and medication adherence using the Short Test of Functional Health Literacy in Adults and the Medication Adherence Rating Scale, respectively. We used validated instruments to assess asthma illness and medication beliefs. We assessed cognition using a cognitive battery. Using structural equation modeling, we modeled illness and medication beliefs as mediators of the relationship between health literacy and adherence while controlling for cognition. RESULTS: Our study included 433 patients with a mean age of 67 +/- 6.8 years. The sample had 84% women, 31% non Hispanic blacks, and 39% Hispanics. The 36% of patients with limited health literacy were more likely to have misconceptions about asthma (P < .001) and asthma medications (P < .001). Health literacy had a direct effect (beta = 0.089; P < .001) as well as an indirect effect on adherence mediated by medications concerns (beta = 0.033; P = .002). Neither medication necessity (beta = 0.044; P = .138) nor illness beliefs (beta = 0.007; P = .143) demonstrated a mediational role between health literacy and adherence. CONCLUSIONS: Interventions designed to improve asthma controller medication adherence in older adults may be enhanced by addressing concerns about medications in addition to using communication strategies appropriate for populations with limited health literacy and cognitive impairments. PMID- 27555455 TI - Early and late B-cell developmental impairment in nuclear factor kappa B, subunit 1-mutated common variable immunodeficiency disease. PMID- 27555456 TI - Pharmacologic inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia. AB - BACKGROUND: Mucosal mast cells (MMCs) play a central role in the development of symptoms associated with IgE-mediated food allergy. Recently, Notch2-mediated signaling was shown to be involved in proper MMC distribution in the intestinal tract. OBJECTIVE: This study aimed to clarify the mechanism by which Notch signaling regulates MMC distribution in the intestinal mucosa. Furthermore, pharmacologic inhibition of Notch signaling was evaluated as a treatment for symptoms associated with experimental food allergy. METHODS: Bone marrow-derived mast cells generated from mice were cultured with Notch ligands, and then expression of genes associated with MMCs was measured in the cells. In addition, the effect of an inhibitor of Notch signaling on food antigen-induced allergic reactions was examined in a mouse model of food allergy. RESULTS: Notch signaling induced MMC differentiation through upregulation of expression of genes characteristic of MMCs in the presence of IL-3. Some lamina propria cells isolated from the mouse small intestine expressed Notch ligands and were able to upregulate MMC markers in bone marrow-derived mast cells through Notch signaling. In a mouse model of food allergy, administration of a Notch signaling inhibitor led to suppression of food antigen-induced hyperplasia of intestinal MMCs, resulting in alleviation of allergic diarrhea and systemic anaphylaxis. CONCLUSION: Notch signaling contributes to differentiation and accumulation of MMCs in the intestinal mucosa. Thus inhibition of Notch signaling alleviates symptoms associated with experimental food allergy. These results raise the possibility that Notch signaling in mast cells is a novel target for therapy in patients with food allergy. PMID- 27555457 TI - Primary T-cell immunodeficiency with functional revertant somatic mosaicism in CD247. PMID- 27555458 TI - Restrictive IL-10 induction by an innocuous parainfluenza virus vector ameliorates nasal allergy. PMID- 27555461 TI - Corrigendum: Static and Dynamical Properties of heavy actinide Monopnictides of Lutetium. PMID- 27555462 TI - Controlling fatigue risk in safety-critical workplaces: A summary of selected papers from the 9th International Conference on Managing Fatigue in Transportation, Resources and Health. PMID- 27555460 TI - Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis. AB - BACKGROUND: Conflicting results have been obtained regarding the roles of Fc receptors and effector cells in models of active systemic anaphylaxis (ASA). In part, this might reflect the choice of adjuvant used during sensitization because various adjuvants might differentially influence the production of particular antibody isotypes. OBJECTIVE: We developed an "adjuvant-free" mouse model of ASA and assessed the contributions of components of the "classical" and "alternative" pathways in this model. METHODS: Mice were sensitized intraperitoneally with ovalbumin at weekly intervals for 6 weeks and challenged intraperitoneally with ovalbumin 2 weeks later. RESULTS: Wild-type animals had immediate hypothermia and late-phase intraperitoneal inflammation in this model. These features were reduced in mice lacking the IgE receptor FcepsilonRI, the IgG receptor FcgammaRIII or the common gamma-chain FcRgamma. FcgammaRIV blockade resulted in a partial reduction of inflammation without any effect on hypothermia. Depletion of monocytes/macrophages with clodronate liposomes significantly reduced the hypothermia response. By contrast, depletion of neutrophils or basophils had no significant effects in this ASA model. Both the hypothermia and inflammation were dependent on platelet-activating factor and histamine and were reduced in 2 types of mast cell (MC)-deficient mice. Finally, engraftment of MC-deficient mice with bone marrow-derived cultured MCs significantly exacerbated the hypothermia response and restored inflammation to levels similar to those observed in wild type mice. CONCLUSION: Components of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for MCs and monocytes/macrophages. PMID- 27555459 TI - Clinical spectrum and features of activated phosphoinositide 3-kinase delta syndrome: A large patient cohort study. AB - BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase delta (PI3Kdelta). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. RESULTS: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kdelta in the central nervous system; consistent with this, PI3Kdelta is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. CONCLUSION: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kdelta inhibitors offer new prospects for APDS treatment. PMID- 27555463 TI - Osteoid osteoma of the pisiform: A case report. AB - BACKGROUND: Osteoid osteoma is an uncommon benign bone-forming tumor of the musculoskeletal system but it is the most common primary bone tumor of the carpal region. However, only seven cases of its pisiform involvement have been described. CASE: We present a 19 year-old male patient with osteoid osteoma of the pisiform which initially could not be detected in any diagnostic study for long standing wrist pain. The patient was treated with excision and curettage. In 1 year of follow-up, the patient was asymptomatic without recurrence. CONCLUSION: In cases with long standing ulnar wrist pain, one should consider osteoid osteoma of the pisiform in differential diagnosis. If an OO is suspected, thin slice CT scan in initial evaluation would be valuable in preventing the patient from misdiagnosis or delay in diagnosis. PMID- 27555464 TI - Improved Compressive Sensing of Natural Scenes Using Localized Random Sampling. AB - Compressive sensing (CS) theory demonstrates that by using uniformly-random sampling, rather than uniformly-spaced sampling, higher quality image reconstructions are often achievable. Considering that the structure of sampling protocols has such a profound impact on the quality of image reconstructions, we formulate a new sampling scheme motivated by physiological receptive field structure, localized random sampling, which yields significantly improved CS image reconstructions. For each set of localized image measurements, our sampling method first randomly selects an image pixel and then measures its nearby pixels with probability depending on their distance from the initially selected pixel. We compare the uniformly-random and localized random sampling methods over a large space of sampling parameters, and show that, for the optimal parameter choices, higher quality image reconstructions can be consistently obtained by using localized random sampling. In addition, we argue that the localized random CS optimal parameter choice is stable with respect to diverse natural images, and scales with the number of samples used for reconstruction. We expect that the localized random sampling protocol helps to explain the evolutionarily advantageous nature of receptive field structure in visual systems and suggests several future research areas in CS theory and its application to brain imaging. PMID- 27555465 TI - Chemotaxis of bio-hybrid multiple bacteria-driven microswimmers. AB - In this study, in a bio-hybrid microswimmer system driven by multiple Serratia marcescens bacteria, we quantify the chemotactic drift of a large number of microswimmers towards L-serine and elucidate the associated collective chemotaxis behavior by statistical analysis of over a thousand swimming trajectories of the microswimmers. The results show that the microswimmers have a strong heading preference for moving up the L-serine gradient, while their speed does not change considerably when moving up and down the gradient; therefore, the heading bias constitutes the major factor that produces the chemotactic drift. The heading direction of a microswimmer is found to be significantly more persistent when it moves up the L-serine gradient than when it travels down the gradient; this effect causes the apparent heading preference of the microswimmers and is the crucial reason that enables the seemingly cooperative chemotaxis of multiple bacteria on a microswimmer. In addition, we find that their chemotactic drift velocity increases superquadratically with their mean swimming speed, suggesting that chemotaxis of bio-hybrid microsystems can be enhanced by designing and building faster microswimmers. Such bio-hybrid microswimmers with chemotactic steering capability may find future applications in targeted drug delivery, bioengineering, and lab-on-a-chip devices. PMID- 27555466 TI - Investigation of active tracking for robotic arm assisted magnetic resonance guided focused ultrasound ablation. AB - BACKGROUND: Focused ultrasound surgery (FUS) is a technique that does not need invasive access to the patient while allowing precise targeted therapy. Magnetic resonance (MR) guided FUS provides capabilities for monitoring treatments. Because the targeted tumours are distributed at different positions, focus repositioning becomes necessary. METHODS: An MR compatible robot was used to increase the operational range of FUS application. Active tracking was developed to detect the robotic arm with regard to the MR coordinate system. The purpose of this study was to construct active tracking to allow a wide spatial range of repositioning the FUS transducer that is fast and accurate. The technique was characterised and validated by a series of positioning tests to prove its efficiency for guiding the robot. RESULTS: In the calibration range, tracking achieved an RMS accuracy of 0.63 mm. Results of phantom ablation showed a focal scanning precision Deltax = 0.4 +/- 0.37 mm, Deltay = 0.4 +/- 0.28 mm and Deltaz = 0.7 +/- 0.66 mm. CONCLUSIONS: The active tracking localisation can be considered a feasible approach for the MR guided FUS system positioned by a robot. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27555467 TI - Special Section on Comorbidity: Introduction. PMID- 27555468 TI - Risk of Childhood Cancer and Socio-economic Disparities: Results of the French Nationwide Study Geocap 2002-2010. AB - BACKGROUND: Socio-economic status is related to many life style and environmental factors, some of which have been suggested to influence the risk of childhood cancer. Studies requiring subject participation are usually hampered by selection of more educated parents. To prevent such bias, we used unselected nationwide Geographical Information System (GIS)-based registry data, to investigate the influence of socio-economic disparities on the risk of childhood cancer. METHODS: The Geocap study included all French residents diagnosed with cancer aged up to 15 years over the period 2002-2010 (15 111 cases) and 45 000 contemporaneous controls representative of the childhood population. Area socio-economic characteristics used to calculate the European Deprivation Index (EDI) were based on census data collected on the fine scale of the Merged Islet for Statistical Information (IRIS). RESULTS: Overall, the risk of acute lymphoblastic leukaemia (ALL) was lower in the most deprived quintile than in the other quintiles of EDI (ORQ5vs36.5 degrees for the identification of lateral and medial perforations, respectively. CONCLUSION: For CPS insertion into the C3-C5 pedicles using CT, there is an increased likelihood of lateral or medial perforation for insertion angles of <24.5 degrees or >36.5 degrees , respectively. PMID- 27555486 TI - The efficacy of interlaminar epidural steroid administration in multilevel intervertebral disc disease with chronic low back pain: a randomized, blinded, prospective study. AB - BACKGROUND CONTEXT: Epidural steroid injection is commonly used in patients with chronic low back pain. Applying a mixture of a local anesthetic (LA) and steroid using the interlaminar (IL), transforaminal, and caudal techniques is a preferred approach. PURPOSE: The present study aims to investigate the efficacy of interlaminar epidural steroid administration in patients with multilevel lumbar disc pathology (LDP) and to assess the possible correlation of the procedure's success with age and body mass index (BMI). STUDY DESIGN: A randomized controlled trial was performed. PATIENT SAMPLE: We administered interlaminar epidural steroid to a total of 98 patients with multilevel LDP. OUTCOME MEASURES: The visual analog scale (VAS) and Oswestry Disability Index (ODI) scoring were performed on the study population at pretreatment (PRT), posttreatment, and 1, 3, 6, and 12 PRT months. A possible correlation of BMI and age with the procedure success was evaluated. METHODS: The LA group (Group L, n=50) received 10 mL 0.25% bupivacaine, whereas the steroid+LA group (Group S, n=48) received 10 mL 0.25% bupivacaine+40 mg methylprednisolone at L4-L5 intervertebral space in prone position under the guidance of C-arm fluoroscopy. RESULTS: There was no statistical difference in the PRT VAS and ODI scores between the groups (p<.05), whereas the VAS and ODI scores at 1, 3, 6, and 12 posttreatment months were higher in Group L, compared with Group S (p<.05). Age and BMI were not found to be related with the success of the procedure. CONCLUSIONS: Our study results showed that the VAS and ODI scores were lower in patients with multilevel LDP receiving steroid, following the administration of IL epidural injection. However, further studies are required to establish a robust conclusion on the dispersion of IL epidural injections in the epidural area and the dose of steroid. PMID- 27555488 TI - Validation of an electrophoretic method to detect albuminuria in cats. AB - Objectives The aims of this study were to validate a semi-automated high resolution electrophoretic technique to quantify urinary albumin in healthy and diseased cats, and to evaluate its diagnostic performance in cases of proteinuria and renal diseases. Methods Urine samples were collected from 88 cats (healthy; chronic kidney disease [CKD]; lower urinary tract disease [LUTD]; non-urinary tract diseases [OTHER]). Urine samples were routinely analysed and high resolution electrophoresis (HRE) was performed. Within-assay and between-assay variability, linearity, accuracy, recovery and the lowest detectable and quantifiable bands were calculated. Receiver operating curve (ROC) analysis was also performed. Results All coefficients of variation were <10%, percentage recovery was between 97% and 109% with a high linearity (r = 0.99). HRE allowed the visualisation of a faint band of albumin and a diffused band between alpha and beta zones in healthy cats, while profiles from diseased cats were variable. Albumin (mg/dl) and urine albumin:creatinine ratio (UAC) were significantly ( P <0.05) different between healthy and diseased cats. After ROC analysis, UAC values of 0.035 and 0.074 had a high sensitivity and high specificity, respectively, to classify proteinuria and identify borderline proteinuric cats. Moreover, a UAC of 0.017 had a high sensitivity in distinguishing between healthy and diseased cats. However, UAC was not able to distinguish between renal (CKD) and non-renal diseases (LUTD/OTHER), probably owing to the pathophysiology of CKD in cats, which is characterised by low-grade proteinuria and less glomerular involvement than in dogs. Conclusions and relevance HRE is an accurate and precise method that could be used to measure albuminuria in cats. UAC was useful to correctly classify proteinuria and to discriminate between healthy and diseased cats. HRE might also provide additional information on urine proteins with a profile of all proteins (albumin and globulins) to aid clinicians in the diagnosis of diseases characterised by proteinuria. PMID- 27555487 TI - Associations of Premenopausal Hysterectomy and Oophorectomy With Breast Cancer Among Black and White Women: The Carolina Breast Cancer Study, 1993-2001. AB - Black women experience higher rates of hysterectomy than other women in the United States. Although research indicates that premenopausal hysterectomy with bilateral oophorectomy decreases the risk of breast cancer in black women, it remains unclear how hysterectomy without ovary removal affects risk, whether menopausal hormone therapy use attenuates inverse associations, and whether associations vary by cancer subtype. In the population-based, case-control Carolina Breast Cancer Study of invasive breast cancer in 1,391 black (725 cases, 666 controls) and 1,727 white (939 cases, 788 controls) women in North Carolina (1993-2001), we investigated the associations of premenopausal hysterectomy and oophorectomy with breast cancer risk. Compared with no history of premenopausal surgery, bilateral oophorectomy and hysterectomy without oophorectomy were associated with lower odds of breast cancer (for bilateral oophorectomy, multivariable-adjusted odds ratios = 0.60, 95% confidence interval: 0.47, 0.77; for hysterectomy without oophorectomy, multivariable-adjusted odds ratios = 0.68, 95% confidence interval: 0.55, 0.84). Estimates did not vary by race and were similar for hormone receptor-positive and hormone receptor-negative cancers. Use of estrogen-only menopausal hormone therapy did not attenuate the associations. Premenopausal hysterectomy, even without ovary removal, may reduce the long-term risk of hormone receptor-positive and hormone receptor-negative breast cancers. Varying rates of hysterectomy are a potentially important contributor to differences in breast cancer incidence among racial/ethnic groups. PMID- 27555489 TI - Frequency of electrophoretic changes consistent with feline infectious peritonitis in two different time periods (2004-2009 vs 2013-2014). AB - Objectives The aim of this study was to evaluate whether the frequency of electrophoretic changes in serum of cats with feline infectious peritonitis (FIP) changed in recent years vs past years. Methods Agarose gel electrophoresis (AGE) and capillary zone electrophoresis (CZE) from cats with FIP and healthy cats recorded in the periods 2004-2009 and 2013-2014 were retrospectively analysed. Relative and absolute values of each electrophoretic fraction were recorded and the number of cats showing single or combined electrophoretic changes consistent with FIP (hypoalbuminaemia, inverted albumin to globulin [A:G] ratio, increased total protein, total globulin, alpha [alpha]2-globulin and gamma [gamma]-globulin concentration) were counted. Additionally, a visual analysis of electrophoretograms was also performed. Results for the two time periods were statistically compared. Results The details of 91 AGE procedures (41 from cats with FIP and 50 from healthy cats) and 45 CZE procedures (26 from cats with FIP and 19 from healthy cats) were obtained from the database. No significant differences between the two time periods were found both in FIP and in healthy cats analysed with CZE and in healthy cats analysed with AGE. Compared with 2004 2009, cats with FIP sampled in 2013-2014 with AGE showed a significantly lower concentration of total protein, gamma-globulins and total globulins, and a significantly higher A:G ratio and percentage of albumin and alpha2-globulins. Using both AGE and CZE, in recent years the proportion of cats with high alpha2 globulins without gammopathy and the proportion of cats with gammopathy alone decreased. With a visual approach, the number of patterns considered as dubious increased in the second period with AGE (non-statistically significant). Conclusions and relevance The frequency of electrophoretic abnormalities in cats with FIP decreased in recent years, independently of the technique employed. Although the mechanism responsible for this change was not investigated in this study, this altered frequency may decrease the diagnostic accuracy of serum protein electrophoresis for FIP. PMID- 27555490 TI - Relation Between Intelligence and Family Size, Position, and Income in Adolescent Girls in Saudi Arabia. AB - Data are reported showing statistically significant negative correlations between intelligence and family size, position, and income in a sample of 604 adolescent girls in Saudi Arabia. There were no statistically significant correlations or associations between whether the mother or father were deceased or both parents were alive, and whether the parents were living together or were divorced. PMID- 27555491 TI - ADHD, learning difficulties and sleep disturbances associated with KCNJ11-related neonatal diabetes. AB - OBJECTIVES: Mutations in KCNJ11 are the most common cause of permanent neonatal diabetes mellitus (NDM). Approximately 25% of patients have obvious neurological dysfunction, but whether milder related problems might be more common has been unclear. We sought to assess the prevalence of parental concerns about learning, behavior, attention deficit hyperactivity disorder (ADHD), social competency, and sleep in subjects with KCNJ11-related NDM compared to unaffected sibling controls. STUDY DESIGN: Subjects or their guardians in the University of Chicago Monogenic Diabetes Registry completed a survey examining learning, behavior, ADHD and sleep. Thirty subjects with KCNJ11 -related NDM and 25 unaffected sibling controls were assessed. Data were analyzed using GraphPad Prism 6. Nonparametric analysis was performed using Fisher's exact test for group comparisons. RESULTS: Thirteen (43%) individuals with KCNJ11 -related NDM had treatment for or a diagnosis of ADHD compared to two (8%) of the sibling controls (P < 0.05). Compared to their sibling controls, individuals with KCNJ11 mutations had significant differences in behavior difficulties, social awareness, academic achievement and the need for an Individualized Education Plan (IEP). As seen in other neurodevelopmental disorders, individuals with KCNJ11 mutations also had significantly higher rates of sleep difficulties (P < 0.01). CONCLUSION: Patients with KCNJ11 -related NDM are at an increased risk for delays in learning, social emotional and behavioral development, ADHD and sleep difficulties based on parent report. Early identification, along with integrated medical and developmental support, may promote better neurodevelopmental outcomes for this unique population. Further investigation utilizing detailed neuropsychological testing will better define the neurodevelopmental consequences of KATP mutations. PMID- 27555492 TI - Insights into kinetic mechanism of Janus kinase 3 and its inhibition by tofacitinib. AB - JAK3 kinase plays a critical role in several cytokine signaling pathways involved in immune cell development and function. The studies presented in this report were undertaken to elucidate the kinetic mechanism of the JAK3 kinase domain, investigate the role of activation loop phosphorylation in regulating its catalytic activity, and examine its inhibition by the anti-rheumatoid arthritis drug, tofacitinib. Phosphorylation of two Tyr residues in JAK3's activation loop has been reported to impact its kinase activity. The recombinant JAK3 kinase domain used in our studies was heterogeneous in its activation loop phosphorylation, with the non-phosphorylated protein being the dominant species. Kinetic analysis revealed similar kinetic parameters for the heterogeneously phosphorylated JAK3, JAK3 mono-phosphorylated on Tyr 980, and the activation loop mutant YY980/981FF. Bisubstrate and product inhibition kinetic results were consistent with both sequential random and sequential ordered kinetic mechanisms. Solvent viscosometric experiments showed perturbation of kcat, suggesting the phosphoryl transfer step is not likely rate limiting. This was supported by results from quench-flow experiments, where a rapid burst of product formation was observed. Kinetic analysis of JAK3 inhibition by tofacitinib indicated inhibition is time dependent, characterized by on- and off-rate constants of 1.4 +/- 0.1 MUM-1s-1 and 0.0016 +/- 0.0005 s-1, respectively. PMID- 27555494 TI - Magnesium cations assist with unpairing hydrogen-bonded 2-deoxyribose trinucleotides. AB - 2-deoxyribose trinucleotides are essential units for storage and transfer of the genetic information. Nucleotide transpositions in trinucleotide sequences affect production of different amino acids. The study focuses on the mechanism of unpairing initially H-bonded trinucleotides. In living cells, the unpairing proceeds through DNA polymerase operating only in the presence of Mg cations. The DNA polymerase is a very complex system to be studied quantum chemically. In our simplistic approach, the polymerase is replaced by two Mg cations attached to both sides of the complementary trinucleotides. A distinguished feature of Mg in cell is in its easiness to accept and donate the electron density. In a particular molecular configuration, this makes Mg singly charged. As to the current case, we observe an unpaired electron on the Mg(+) and an unpaired electron on the trinucleotide - totally, a radical pair which coupling produces either triplet or singlet state. The study, based on the DFT B3LYP (6-311G** basis set) computations, shows that the singlet state energetically is less preferable than the triplet state. The latter is unstable and makes the trinucleotide strands unpair in the region where the singlet and triplet states cross. PMID- 27555493 TI - The chemical biology of HNO signaling. AB - Nitroxyl (HNO) is a simple molecule with significant potential as a pharmacological agent. For example, its use in the possible treatment of heart failure has received recent attention due to its unique therapeutic properties. Recent progress has been made on the elucidation of the mechanisms associated with its biological signaling. Importantly, the biochemical mechanisms described for HNO bioactivity are consistent with its unique and novel chemical properties/reactivity. To date, much of the biology of HNO can be associated with interactions and modification of important regulatory thiol proteins. Herein will be provided a description of HNO chemistry and how this chemistry translates to some of its reported biological effects. PMID- 27555495 TI - Comments on Methods to Suppress Endogenous beta-Galactosidase Activity in Mouse Tissues Expressing the LacZ Reporter Gene. AB - The Escherichia coli LacZ gene (encoding beta-galactosidase) is a widely used reporter for gene regulation analysis in transgenic mice. Determination of beta galactosidase activity is classically performed using 5-bromo-4-chloro-3-indolyl beta-d-galactopyranoside/ferri-/ferrocyanide (X-Gal/FeCN) histochemistry. Uncertainty about the origin of the beta-galactosidase signal is encountered in tissues containing high levels of endogenous beta-galactosidase. Here, we show that reliable results can nevertheless be obtained in these tissues by performing the histochemical reaction under slightly basic pH conditions (pH 8-9). We further demonstrate that in this context, analysis of tissue sections may be advantageous over that of conventional whole-mount tissues because poor dye penetration and remaining tissue acidity are avoided in tissue sections. We also recommend that bacterial debris should always be carefully removed from the luminal surface of gastrointestinal tract specimens unless staining of resident microflora is deliberately used as an internal positive control in the assay. Finally, we show that 6-chloro-3-indolyl-beta-d-galactopyranoside with nitrotetrazolium blue chloride works well as an alternative chromogenic substrate for visualizing LacZ reporter gene expression in cryostat sections. Its use in high endogenous beta-galactosidase-expressing organs is superior over the use of X-Gal/FeCN at slightly basic pH conditions. PMID- 27555496 TI - Root-mediated signal transmission of systemic acquired resistance against above ground and below-ground pathogens. AB - BACKGROUND AND AIMS: Plants modulate defence signalling networks in response to various biotic stresses via inter-organ communications. The root-mediated transmission of systemic acquired resistance (SAR) against soil-borne and air borne plant pathogens from SAR-induced plants to neighbouring plants subjected to local chemical and pathogen treatments was evaluated. METHODS: The first two plants out of ten Nicotiana benthamiana seedlings were pre-treated with the SAR triggering chemical benzothiadiazole (BTH). All ten seedlings were then challenged with two pathogenic bacteria, i.e. the root (bacterial wilt) pathogen Ralstonia solanacearum and the leaf (wildfire) pathogen Pseudomonas syringae pv. tabaci, at 7 d after SAR induction. KEY RESULTS: Disease severity was noticeably lower in BTH-pre-treated plants than in the control. Surprisingly, two plants located next to BTH-treated plants exhibited reduced disease symptoms indicating that SAR signal transmission occurred through the root system. Determinant(s) secreted from the root system were search for and it was found that salicylic acid (SA) is a major molecule involved in SAR transmission through the root. Analysis of the expression of the defence-related genes N. benthamiana pathogenesis-related gene 1a (NbPR1a) and NbPR2 confirmed that BTH treatment elicited SAR via root-root transmission between plants. Plants with knock-down of the multiple resistance component SGT1 and SA biosynthesis-related gene ICS1 by Tobacco rattle virus-mediated virus-induced gene silencing exhibited a lack of root-mediated SAR transmission. The biological relevance of this finding was validated by challenge with the SAR-inducing avirulent pathogen P. syringae pv. syringae instead of BTH, which produced similar results. CONCLUSIONS: Our findings demonstrated that SAR is transmissible through the root system from SAR triggered plants to neighbouring plants. PMID- 27555498 TI - Clinical Scholarship: Let's Share What We Are Doing in Practice to Improve Outcomes. PMID- 27555497 TI - Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing. AB - Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC. PMID- 27555499 TI - Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes. AB - We recently described an inducible human TNF transgenic mouse line (ihTNFtg) that develops psoriasis-like arthritis after doxycycline stimulation and analysed the pathogenesis of arthritis in detail. Here, we show that the skin phenotype of these mice is characterized by hyperproliferation and aberrant activation of keratinocytes, induction of pro-inflammatory cytokines, and infiltration with Th1 and Treg lymphocytes, particularly with macrophage infiltration into lesional skin, thus pointing to a psoriasis-like phenotype. To reveal the contribution of T cells and macrophages to the development of TNF-mediated psoriasis, ihTNFtg mice were crossbred into RAG1KO mice lacking mature T and B cells. Surprisingly, the psoriatic phenotype in the double mutants was not reduced; rather, it was enhanced. The skin showed significantly increased inflammation and in particular, increased infiltration by macrophages. Consequently, depletion of macrophages in RAG1KO or wild-type mice led to decreased disease severity. On the contrary, depletion of Treg cells in wild-type mice increased both psoriasis and the number of infiltrating macrophages, while adoptive transfer of Foxp3-positive cells into RAG1KO or wild-type mice decreased both the development of psoriasis and macrophage infiltration. Thus, we conclude that Treg lymphocytes inhibit the pro inflammatory activity of macrophages, which are the major immune effector cells in hTNF-mediated psoriasis. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27555500 TI - Refining and validating a conceptual model of Clinical Nurse Leader integrated care delivery. AB - AIMS: To empirically validate a conceptual model of Clinical Nurse Leader integrated care delivery. BACKGROUND: There is limited evidence of frontline care delivery models that consistently achieve quality patient outcomes. Clinical Nurse Leader integrated care delivery is a promising nursing model with a growing record of success. However, theoretical clarity is necessary to generate causal evidence of effectiveness. DESIGN: Sequential mixed methods. METHODS: A preliminary Clinical Nurse Leader practice model was refined and survey items developed to correspond with model domains, using focus groups and a Delphi process with a multi-professional expert panel. The survey was administered in 2015 to clinicians and administrators involved in Clinical Nurse Leader initiatives. Confirmatory factor analysis and structural equation modelling were used to validate the measurement and model structure. RESULTS: Final sample n = 518. The model incorporates 13 components organized into five conceptual domains: 'Readiness for Clinical Nurse Leader integrated care delivery'; 'Structuring Clinical Nurse Leader integrated care delivery'; 'Clinical Nurse Leader Practice: Continuous Clinical Leadership'; 'Outcomes of Clinical Nurse Leader integrated care delivery'; and 'Value'. Sample data had good fit with specified model and two-level measurement structure. All hypothesized pathways were significant, with strong coefficients suggesting good fit between theorized and observed path relationships. CONCLUSIONS: The validated model articulates an explanatory pathway of Clinical Nurse Leader integrated care delivery, including Clinical Nurse Leader practices that result in improved care dynamics and patient outcomes. The validated model provides a basis for testing in practice to generate evidence that can be deployed across the healthcare spectrum. PMID- 27555502 TI - How Food Intakes Modify Testosterone Level. PMID- 27555501 TI - Regeneration in bipinnaria larvae of the bat star Patiria miniata induces rapid and broad new gene expression. AB - BACKGROUND: Some metazoa have the capacity to regenerate lost body parts. This phenomenon in adults has been classically described in echinoderms, especially in sea stars (Asteroidea). Sea star bipinnaria larvae can also rapidly and effectively regenerate a complete larva after surgical bisection. Understanding the capacity to reverse cell fates in the larva is important from both a developmental and biomedical perspective; yet, the mechanisms underlying regeneration in echinoderms are poorly understood. RESULTS: Here, we describe the process of bipinnaria regeneration after bisection in the bat star Patiria miniata. We tested transcriptional, translational, and cell proliferation activity after bisection in anterior and posterior bipinnaria halves as well as expression of SRAP, reported as a sea star regeneration associated protease (Vickery et al., 2001b). Moreover, we found several genes whose transcripts increased in abundance following bisection, including: Vasa, dysferlin, vitellogenin 1 and vitellogenin 2. CONCLUSION: These results show a transformation following bisection, especially in the anterior halves, of cell fate reassignment in all three germ layers, with clear and predictable changes. These results define molecular events that accompany the cell fate changes coincident to the regenerative response in echinoderm larvae. PMID- 27555503 TI - Preserved Erectile Function in the Aged Transgenic Rat Harboring Human Tissue Kallikrein 1. AB - INTRODUCTION: Human tissue kallikrein 1 (hKLK1) has enormous potential for the protection of vasodilation and endothelial function in the cardiovascular system. Our previous study proved the decreased expression of kallikrein 1 in the corpus cavernosum (CC) of aged rats, but the role of kallikrein 1 in age-related erectile dysfunction remains unknown. AIM: To explore the effect and underlying mechanisms of hKLK1 on age-related erectile dysfunction. METHODS: Male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 27 months of age, respectively, and divided into four groups: young WTR (yWTR) as the control, young TGR (yTGR), aged WTR (aWTR), and aged TGR (aTGR). Rats' erectile function was evaluated by the cavernous nerve electrostimulation method. Then, CCs were collected for verification of hKLK1 followed by measurement of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) and RhoA-Rho-kinase (ROCK) signaling activities. Masson trichrome staining and terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling assay were conducted to evaluate penile fibrosis and apoptosis. MAIN OUTCOME MEASURES: Erectile response, NO-cGMP and RhoA-ROCK pathway-related indices, ratio of smooth muscle to collagen, and apoptosis index. RESULTS: The hKLK1 alleviated the decrease of erectile function in the aWTR group. Endothelial NO synthase (eNOS) and phospho-eNOS(Ser1177) expressions, NO synthase activity, and NO and cGMP levels were decreased, whereas phospho-eNOS(Thr495), L-type Ca(2+) channel, RhoA, ROCK1, ROCK2, and transforming growth factor beta1 proteins were increased in the CCs of the aWTR group compared with the control yWTR group. These changes were obviously mitigated in the aTGR group. Moreover, hKLK1 prevented the sharp decrease of the ratio of smooth muscle to collagen and the increase of the apoptosis index in the CCs of the aWTR group. CONCLUSION: These results suggest that hKLK1 could play a preventive role in age-related erectile dysfunction by activation of the NO-cGMP pathway and inhibition of the RhoA-ROCK pathway and by antitissue fibrotic and apoptotic effects. PMID- 27555504 TI - Editorial Commentary on Miner and Colleagues' Study: Understanding the Personality and Behavioral Mechanisms Defining Hypersexuality in Men Who Have Sex With Men. PMID- 27555506 TI - High Triglycerides Predicts Arteriogenic Erectile Dysfunction and Major Adverse Cardiovascular Events in Subjects With Sexual Dysfunction. AB - INTRODUCTION: The atherogenic role of triglycerides (TG) remains controversial. The aim of the present study is to analyze the contribution of TG in the pathogenesis of erectile dysfunction (ED) and to verify the value of elevated TG in predicting major adverse cardiovascular events (MACE). METHODS: An unselected series of 3,990 men attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of this sample (n = 1,687) was enrolled in a longitudinal study. MAIN OUTCOME MEASURES: Several clinical, biochemical, and instrumental (penile color Doppler ultrasound; PCDU) factors were evaluated. RESULTS: Among the patients studied, after adjustment for confounders, higher TG levels were associated with arteriogenic ED and a higher risk of clinical and biochemical hypogonadism. Conversely, no association between TG and other sexual dysfunctions was observed. When pathological PCDU parameters-including flaccid acceleration (<1.17 m/sec(2)) or dynamic peak systolic velocity (PSV <35 cm/sec) were considered, the negative association between impaired penile flow and higher TG levels was confirmed, even when subjects taking lipid-lowering drugs or those with diabetes were excluded from the analysis (OR = 6.343 [1.243;32.362], P = .026 and 3.576 [1.104;11.578]; P = .34 for impaired acceleration and PSV, respectively). Similarly, when the same adjusted models were applied, TG levels were associated with a higher risk of hypogonadism, independently of the definition criteria (OR = 2.892 [1.643;5.410], P < .0001 and 4.853 [1.965;11.990]; P = .001 for total T <12 and 8 nM, respectively). In the longitudinal study, after adjusting for confounders, elevated TG levels (upper quartile: 162-1686 mg/dL) were independently associated with a higher incidence of MACE (HR = 2.469 [1.019;5.981]; P = .045), when compared to the rest of the sample. CONCLUSION: Our data suggest an association between elevated TG and arteriogenic ED and its cardiovascular (CV) risk stratification. Whether the use of TG lowering drugs might improve ED and its associated CV risk must be confirmed through specific trials. PMID- 27555505 TI - Blood Pressure, Sexual Activity, and Dysfunction in Women With Hypertension: Baseline Findings From the Systolic Blood Pressure Intervention Trial (SPRINT). AB - INTRODUCTION: Sexual function, an important component of quality of life, is gaining increased research and clinical attention in older women with hypertension. AIM: To assess the association between systolic blood pressure (SBP) and other variables, and sexual activity and sexual dysfunction in hypertensive women. METHODS: Baseline analysis of 635 women participants of a larger randomized clinical trial of 9361 men and women. MAIN OUTCOME MEASURES: Self-reported sexual activity (yes/no), and sexual function using the Female Sexual Function Inventory (FSFI). RESULTS: 452 participants (71.2%) reported having no sexual activity during the previous 4 weeks. The mean (SD) FSFI score for sexually active participants was 25.3 (6.0), and 52.6% of the sample reported a FSFI score <=26.55 designating sexual dysfunction. In logistic regression models, SBP was not significantly associated with sexual activity (AOR = 1.002; P > .05). Older age (AOR = 0.95, P < .05), and lower education (AOR for < high school vs college degree = 0.29, P < .05) were associated with lower odds of being sexually active, as was living alone versus living with others (AOR = 0.56, P < .05). Higher weekly alcohol consumption was associated with increased odds of being sexually active (AOR = 1.39; P < .05). In logistic regression models among sexually active participants, SBP was not associated with sexual dysfunction (AOR = 1.01; P > .05). Higher depressive symptoms from the Patient Health Questionnaire-9 (PHQ-9) was associated with higher odds of sexual dysfunction (AOR = 1.24, P < .05), as was increased number of physical comorbidities (AOR = 1.25, P < .05). Diuretic use was associated with lower odds of being sexually active in participants with chronic kidney disease (AOR = 0.33, P < .05). CONCLUSION: Younger age, higher education, living with others, and higher weekly alcohol consumption were significantly associated with higher odds of being sexually active in a sample of middle-aged and older women with hypertension. Increased depressive symptoms and increased physical comorbidities were significantly associated with increased odds of sexual dysfunction. SBP was not significantly associated with sexual activity or sexual dysfunction. PMID- 27555507 TI - Sexual Response Models: Toward a More Flexible Pattern of Women's Sexuality. AB - INTRODUCTION: Recent research suggests that none of the current theoretical models can sufficiently describe women's sexual response, because several factors and situations can influence this. AIM: To explore individual variations of a sexual model that describes women's sexual responses and to assess the association of endorsement of that model with sexual dysfunctions and reasons to engage in sexual activity. METHODS: A sample of 157 randomly selected hospital employees completed self-administered questionnaires. MAIN OUTCOME MEASURES: Two models were developed: one merged the Master and Johnson model with the Kaplan model (linear) and the other was the Basson model (circular). Sexual function was evaluated by the Female Sexual Function Index and the Brief Sexual Symptom Checklist for Women. The Reasons for Having Sex Questionnaire was administered to investigate the reasons for which women have sex. RESULTS: Women reported that their current sexual experiences were at times consistent with the linear and circular models (66.9%), only the linear model (27%), only the circular model (5.4%), and neither model (0.7%). When the groups were reconfigured to the group that endorsed more than 5 of 10 sexual experiences, 64.3% of women endorsed the linear model, 20.4% chose the linear and circular models, 14.6% chose the circular model, and 0.7% selected neither. The Female Sexual Function Index, demographic factors, having sex for insecurity reasons, and sexual satisfaction correlated with the endorsement of a sexual response model. When these factors were entered in a stepwise logistic regression analysis, only the Female Sexual Function Index and having sex for insecurity reasons maintained a significant association with the sexual response model. CONCLUSION: The present study emphasizes the heterogeneity of female sexuality, with most of the sample reporting alternating between the linear and circular models. Sexual dysfunctions and having sex for insecurity reasons were associated with the Basson model. PMID- 27555508 TI - Opioids Increase Sexual Dysfunction in Patients With Non-Cancer Pain. AB - INTRODUCTION: Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated. AIM: To analyze the presence of SD in a large group of patients receiving long-term opioids. METHODS: A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects. MAIN OUTCOME MEASURES: Sexual function was determined by the Female Sexual Function Index (FSFI; scores = 2-36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores = 1-30). RESULTS: Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P < .05), although they reported having a regular partner (84% vs 70%, P = .03) and a sexually active life (69% vs 34%, respectively, P = .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median = 70 mg/d, interquartile range = 43.1-170, 115.5 +/- 110.3 mg/d vs median = 60 mg/d, interquartile range = 30-100.6, 76.67 +/- 63.79 mg/d, P = .016) at the same mean intensity of pain (P = .54), which correlated to FSFI scores (r = -0.313, P = .01). CONCLUSION: SD is prevalent in patients with CNP and higher in men who received a significantly higher mean opioid dose at the same intensity pain level than women. The morphine equivalent dose was correlated to SD intensity. Evidence-based interventions to support sexual activity and function in CNP are needed. PMID- 27555509 TI - The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction. AB - INTRODUCTION: An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. AIM: To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. METHODS: A consecutive series of 2833 men (mean age 50.2 +/- 13.5 years) was retrospectively studied. MAIN OUTCOME MEASURES: Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). RESULTS: Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P < .05). Moreover, they reported a general impairment of their sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P < .005). Interestingly, we observed a significant association between MHQ-S scoring with a reduced testosterone level and hypogonadism symptoms (both P < .05). Finally, we found a significant association between somatic symptoms and both SIEDY Scales 1 (organic domain of ED) and 3 (intrapsychic domain of ED) (both P < .0001). CONCLUSION: The present study demonstrates that the presence of somatic symptoms can represent an important contextual factor in the determination of or in the exacerbation of male sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality. PMID- 27555510 TI - Initial Validation of the Sexual Pleasure Scale in Clinical and Non-Clinical Samples of Partnered Heterosexual People. AB - INTRODUCTION: Sexual pleasure is a central aspect of human sexuality; however, no validated measurements exist that assess sexual pleasure. We present a preliminary validation study of the psychometric properties of a Sexual Pleasure Scale (SPS), based on the three items developed by Sanchez, Crocker and Boike to measure sexual pleasure. The SPS is a brief and easy-to-implement instrument that assesses the extent of sexual pleasure experienced from sexual relationships, sexual activities, and sexual intimacy. AIM: To assess the validity of the SPS in a subgroup of patients diagnosed with sexual dysfunction (n = 89) and a non clinical community sample (n = 188) of Portuguese men and women. METHODS: We provide an initial examination of the reliability (eg, Cronbach alpha), convergent validity (eg, with measurements of sexual satisfaction), and divergent validity (eg, with measurements of body satisfaction) of the SPS. MAIN OUTCOME MEASURES: The survey included a sociodemographic questionnaire and a set of questionnaires to test the psychometric properties of the SPS. RESULTS: The reliability study showed a high Cronbach value (alpha = 0.94). Convergent validity of the SPS with the measurements described showed mostly moderate to high statistically significant positive correlations, whereas the criterion related validity showed the expected low non-significant correlation. The results also showed that the SPS shows strong sensitivity to discriminate people with from those without sexual problems. CONCLUSION: Results from the clinical population indicate that the SPS has good psychometric qualities and is a reliable measurement of sexual pleasure with applicability in clinical practice and clinical research but shows little variability within the community sample. PMID- 27555511 TI - Editorial Comment on "Penile Girth Enhancement With PMMA-Based Soft Tissue Fillers". PMID- 27555512 TI - Response and Rebuttal to Editorial Comment Regarding "Penile Girth Enhancement With PMMA-Based Soft Tissue Fillers". PMID- 27555513 TI - Is Risk of Artificial Urethral Sphincter Cuff Erosion Higher in Patients with Penile Prosthesis? AB - INTRODUCTION: Frequently encountered morbidities after prostatectomy include stress urinary incontinence and erectile dysfunction. Patients with severe disease may undergo placement of both a penile prosthesis (PP) and an artificial urethral sphincter (AUS). AIM: We hypothesized that concomitant PP may promote AUS cuff erosion by impaired corporal blood flow and/or direct pressure on the cuff. The aim of this study was to compare the rate of AUS cuff erosion in patients with and without a PP. METHODS: We reviewed 366 AUS operations at our tertiary center between 2007 and 2015 with a mean follow-up of 41 months (range 6 104). Included in the analysis were first-time AUS cuff erosions. Patients with recurrent erosions, AUS revisions, and iatrogenic erosions were excluded. In a separate analysis, we analyzed AUS explantations for all causes. Cohorts were compared by demographic information, preoperative characteristics, and rates of erosion and explantation. MAIN OUTCOME MEASURES: Erosion confirmed by cystourethroscopy and explantation of the AUS for all causes. RESULTS: Among 366 AUS surgeries at a mean follow-up of 41 months, there were 248 (67.8%) AUS alone cases compared to 118 (32.2%) AUS and PP cases (AUS/PP). Sixty-two patients met exclusion criteria for first-time cuff erosion. Among 304 evaluable AUS patients, we found a significantly higher rate of erosion in the AUS/PP group (11/95, 11.6%) compared to the AUS alone group (9/209, 4.3%, P = .037). When examining explantations for all causes in the entire cohort (n = 366), we observed a significantly higher rate of device removal, (20/118, 17%) in the AUS/PP group compared to the AUS group (23/248, 9.2%, P = .044). CONCLUSION: AUS/PP patients appear to have a higher risk of AUS cuff erosion and explantation compared to men with AUS alone. PMID- 27555515 TI - [Report of the ordinary general assembly of the Morphologists' Association - 18th March 2016]. PMID- 27555514 TI - A mutagenic study identifying critical residues for the structure and function of rice manganese transporter OsMTP8.1. AB - Rice (Oryza sativa) MTP8.1 (OsMTP8.1) is a tonoplast-localized manganese transporter of the cation diffusion facilitator family. Here we present a structure-function analysis of OsMTP8.1 based on the site-directed and random mutagenesis and complementation assays in manganese hypersensitive yeast, in combination with three-dimensional (3D) structure modeling based on the crystal structure of the Escherichia coli CDF family member, EcYiiP. Two metal-binding sites are conserved in OsMTP8.1 with EcYiiP, one is between transmembrane helices TM2 and TM5, the other is the cytoplasmic C-terminus. In addition to these two metal-binding sites, there may exist other Mn-binding sites such as that at the very end of the CTD. Two residues (R167 and L296) may play an important role for the hinge-like movement of CTDs. Several mutations such as E357A and V374D may affect dimer formation, and S132A may induce a conformational change, resulting in a loss of transport function or modification in metal selectivity. The N terminus of OsMTP8.1 was not functional for Mn transport activity, and the real function of NTD remains to be investigated in the future. The findings of the present study illustrate the structure-function relationship of OsMTP8.1 in Mn transport activity, which may also be applied to other plant Mn-CDF proteins. PMID- 27555516 TI - Pancreatic cancer: A role for redox regulation in PDAC. PMID- 27555517 TI - Cutaneous Sarcoid with Livedoid Changes in a Patient with Hashimoto's Thyroiditis. PMID- 27555518 TI - Congenital Plaque-type Glomuvenous Malformation: 11 Years of Follow-up and Response to Treatment With the Combined Pulsed-Dye and Neodymium:Yttrium-Aluminum Garnet Laser. PMID- 27555519 TI - A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria. AB - Fatty acid metabolism is an important feature of the pathogenicity of Mycobacterium tuberculosis during infection. Consumption of fatty acids requires regulation of carbon flux bifurcation between the oxidative TCA cycle and the glyoxylate shunt. In Escherichia coli, flux bifurcation is regulated by phosphorylation-mediated inhibition of isocitrate dehydrogenase (ICD), a paradigmatic example of post-translational mechanisms governing metabolic fluxes. Here, we demonstrate that, in contrast to E. coli, carbon flux bifurcation in mycobacteria is regulated not by phosphorylation but through metabolic cross activation of ICD by glyoxylate, which is produced by the glyoxylate shunt enzyme isocitrate lyase (ICL). This regulatory circuit maintains stable partitioning of fluxes, thus ensuring a balance between anaplerosis, energy production, and precursor biosynthesis. The rheostat-like mechanism of metabolite-mediated control of flux partitioning demonstrates the importance of allosteric regulation during metabolic steady-state. The sensitivity of this regulatory mechanism to perturbations presents a potentially attractive target for chemotherapy. PMID- 27555520 TI - Dense water plumes modulate richness and productivity of deep sea microbes. AB - Growing evidence indicates that dense water formation and flow over the continental shelf is a globally relevant oceanographic process, potentially affecting microbial assemblages down to the deep ocean. However, the extent and consequences of this influence have yet to be investigated. Here it is shown that dense water propagation to the deep ocean increases the abundance of prokaryotic plankton, and stimulates carbon production and organic matter degradation rates. Dense waters spilling off the shelf modifies community composition of deep sea microbial assemblages, leading to the increased relevance of taxa likely originating from the sea surface and the seafloor. This phenomenon can be explained by a combination of factors that interplay during the dense waters propagation, such as the transport of surface microbes to the ocean floor (delivering in our site 0.1 megatons of C), the stimulation of microbial metabolism due to increased ventilation and nutrients availability, the sediment re-suspension, and the mixing with ambient waters along the path. Thus, these results highlight a hitherto unidentified role for dense currents flowing over continental shelves in influencing deep sea microbes. In light of climate projections, this process will affect significantly the microbial functioning and biogeochemical cycling of large sectors of the ocean interior. PMID- 27555522 TI - Synergistic Diazo-OH Insertion/Conia-Ene Cascade Catalysis for the Stereoselective Synthesis of gamma-Butyrolactones and Tetrahydrofurans. AB - A novel and highly efficient diazo-OH insertion/Conia-ene cascade reaction of readily available homopropargylic acids and alcohols with diazo carbonyl compounds is described. The cascade reaction involves a synergistic Rh/Ag/Au catalyst cocktail and proceeds instantly with a variety of substituted diazo compounds and acids/alcohols to provide functionalized gamma-butyrolactones and tetrahydrofurans with complete regio- and stereoselectivity. The unprecedented rate-enhancement, complete stereoselectivity, and the enabling of new Conia-ene cyclizations suggest a concerted [4+1]-cycloaddition reaction pathway under synergistic (Rh/Ag/Au)-catalysis conditions. PMID- 27555521 TI - TGEV infection up-regulates FcRn expression via activation of NF-kappaB signaling. AB - It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up regulated pFcRn expression. In addition, the NF-kappaB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV infected IPEC-J2 cells with the NF-kappaB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-kappaB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-kappaB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-kappaB signaling. PMID- 27555523 TI - Health care institutional charges associated with ambulatory bloodstream infections in pediatric oncology and stem cell transplant patients. AB - BACKGROUND: The impact of ambulatory bloodstream infections (Amb-BSIs) in pediatric oncology and stem cell transplant (PO/SCT) patients is poorly understood, although a large portion of their treatment increasingly occurs in this setting. This study aimed to understand the economic impact and length of stay (LOS) associated with these infections. PROCEDURE: Charges and LOS were retrospectively collected and analyzed for Amb-BSI events leading to a hospital admission between 2012 and 2013 in a tertiary, university-affiliated hospital. Events were grouped as BSI-MIXED when hospitalizations with care unrelated to the infection-extended LOS by more than 24 hr or as BSI-PURE for all others. Billing codes were used to group charges and main drivers were analyzed. RESULTS: Seventy four BSI events were identified in 61 patients. Sixty-nine percent met definition for central line-associated BSI (CLABSI). Median total charge and LOS for an Amb BSI were $40,852 (interquartile range [IQR] $44,091) and 7 days (IQR 6), respectively. Median charges for BSI-PURE group (N = 62) were $36,611 (IQR $34,785) and $89,935 (IQR $153,263) in the BSI-MIXED (N = 12) group. Median LOS was 6 (IQR 5) days in the BSI-PURE group and 15 (IQR 24) in the BSI-MIXED. Room, pharmacy, and procedure charges accounted for more than 70% of total charges in all groups. CONCLUSIONS: Amb-BSIs in PO/SCT patients result in significant healthcare charges and unplanned extended hospital admissions. This analysis suggests that efforts aiming at reducing rates of infections could result in substantial system savings, validating the need for increased efforts to prevent Amb-BSIs. PMID- 27555524 TI - Identification of suitable combinations of in vitro sperm-function test for the prediction of fertility in buffalo bull. AB - The present study assessed sperm functional characteristics in the frozen-thawed semen of buffalo bulls and estimated their relationship with field fertility. Frozen semen samples from three different freezing operations each from nine Murrah buffalo bulls were used for the assessment of different sperm functions related to fertilizing potential. Bulls were classified into high (n = 2), medium (n = 5), and low (n = 2) fertile based on adjusted field fertility. The sperm functions estimated included membrane integrity using carboxyfluorescein diacetate-propidium iodide, acrosome reaction status using fluorescein isothiocyanate peanut agglutinine, status of apoptosis using Annexin-V, protamine deficiency using Chromomycin A3, membrane stability using Merocyanine 540 and lipid peroxidation status using 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene. The relationship between the proportion of live acrosome-intact spermatozoa and fertility was positive and significant (r = 0.59; P = 0.001). The proportion of moribund spermatozoa showed a significantly negative correlation with fertility (r = -0.50; P = 0.008). Similarly, the relationship of spermatozoa with unstable membrane (r = -0.51; P = 0.007), necrotic (r = - 0.42; P = 0.028), early necrotic (r = -0.42; P = 0.031), and apoptotic spermatozoa (r = -0.39; P = 0.046) with bull fertility was negative and significant. The correlation between the protamine-deficient spermatozoa and fertility was negative, but not significant. Among different combinations of tests, live acrosome-intact spermatozoa and lipid peroxidation status of spermatozoa revealed high positive correlation with buffalo bull fertility (adjusted R2 = 0.73, C[p] = 0.80). These preliminary findings may help in developing tools for assessing fertility of buffalo bulls, once validated in more animals. PMID- 27555525 TI - Cryopreservation of animal oocytes and embryos: Current progress and future prospects. AB - Cryopreservation describes techniques that permit freezing and subsequent warming of biological samples without loss of viability. The application of cryopreservation in assisted reproductive technology encompasses the freezing of gametes, embryos, and primordial germ cells. Whilst some protocols still rely on slow-freezing techniques, most now use vitrification, or ultra-rapid freezing, for both oocytes and embryos due to an associated decreased risk of damage caused by the lack of ice crystal formation, unlike in slow-freezing techniques. Vitrification has demonstrated its use in many applications, not only following IVF procedures in human embryology clinics but also following in vitro production of embryos in agriculturally important, or endangered animal species, before embryo transfer. Here, we review the various cryopreservation and vitrification technologies that are used in both humans and other animals and discuss the most recent innovations in vitrification with a particular emphasis on their applicability to animal embryology. PMID- 27555526 TI - Vitamin D receptor is expressed within human carotid plaques and correlates with pro-inflammatory M1 macrophages. AB - The role of Vitamin D system in cardiovascular diseases remains controversial. Here, we investigated whether intraplaque levels of vitamin D receptor (VDR) predicted major adverse cardiovascular events (MACEs) at 18month-follow-up and correlated with macrophage subsets in 164 patients undergoing endarterectomy for carotid stenosis. In human carotid plaque portions upstream and downstream the blood flow, VDR, lipid, collagen, as well as macrophage subsets were determined. Human primary monocytes were then differentiated in vitro to M1 and M2 macrophages and treated with 1,25(OH)2D3. Intraplaque VDR positively correlated with total and M1 macrophages. According to the result of ROC curve analysis, downstream portions of plaques having high VDR expression were characterized by increased M1 macrophages. Kaplan-Meier analysis showed that the risk of MACEs was greater in patients having low downstream VDR levels (8.2% vs. 1.3%; p=0.005). Cox proportional hazard regression analyses confirmed that MACE risk decreased with increasing downstream VDR (adjusted HR 0.78 [95% CI 0.62-0.98]; p=0.032). In vitro, VDR expression was prevalent in M1, but not M2. Incubation of M1 macrophages with 1,25(OH)2D3, increased VDR expression and suppressed toll-like receptor 4 expression. These results suggest that low intraplaque VDR expression predict MACEs in patients with carotid stenosis potentially involving M1 macrophages. PMID- 27555527 TI - Zinc Homeostasis at the Bacteria/Host Interface-From Coordination Chemistry to Nutritional Immunity. AB - Zinc is one of the most important metal nutrients for species from all kingdoms, being a key structural or catalytic component of hundreds of enzymes, crucial for the survival of both pathogenic microorganisms and their hosts. This work is an overview of the homeostasis of zinc in bacteria and humans. It explains the importance of this metal nutrient for pathogens, describes the roles of zinc sensors, regulators, and transporters, and summarizes various uptake systems and different proteins involved in zinc homeostasis-both those used for storage, buffering, and signaling inside the cell and those excreted in order to obtain ZnII from the host. The human zinc-dependent immune system response is explained, with a special focus given to 'zinc nutritional immunity', a process that describes the competition between the bacteria or fungus and the host for this metal, during which both the pathogen and host make huge efforts to control zinc availability. This sophisticated tug of war over ZnII might be considered as a possible target for novel antibacterial therapies. PMID- 27555528 TI - Multimetal-Substituted Epsilon-Iron Oxide epsilon-Ga0.31 Ti0.05 Co0.05 Fe1.59 O3 for Next-Generation Magnetic Recording Tape in the Big-Data Era. AB - From the viewpoints of large capacity, long-term guarantee, and low cost, interest in magnetic recording tapes has undergone a revival as an archive storage media for big data. Herein, we prepared a new series of metal-substituted epsilon-Fe2 O3 , epsilon-Ga(III) 0.31 Ti(IV) 0.05 Co(II) 0.05 Fe(III) 1.59 O3 , nanoparticles with an average size of 18 nm. Ga, Ti, and Co cations tune the magnetic properties of epsilon-Fe2 O3 to the specifications demanded for a magnetic recording tape. The coercive field was tuned to 2.7 kOe by introduction of single-ion anisotropy on Co(II) (S=3/2) along the c-axis. The saturation magnetization was increased by 44 % with Ga(III) (S=0) and Ti(IV) (S=0) substitution through the enhancement of positive sublattice magnetizations. The magnetic tape media was fabricated using an actual production line and showed a very sharp signal response and a remarkably high signal-to-noise ratio compared to the currently used magnetic tape. PMID- 27555530 TI - Asymmetric Hydrogenation of Quinoline Derivatives Catalyzed by Cationic Transition Metal Complexes of Chiral Diamine Ligands: Scope, Mechanism and Catalyst Recycling. AB - This personal account is focused on the asymmetric hydrogenation of quinolines and their analogues recently developed by using phosphorus-free chiral cationic ruthenium(II)/eta6 -arene-N-monosulfonylated diamine complexes. In our initial study, the chiral Ru-diamine complexes were found to be highly effective catalysts for the asymmetric hydrogenation of difficult quinoline substrates in room temperature ionic liquids (RTILs) with unprecedentedly excellent enantioselectivity. Our further systematic study revealed that a wide range of quinoline derivatives could be efficiently hydrogenated in alcoholic solvents, or under solvent-free and concentrated conditions with good to excellent stereoselectivity. Complexes of iridium analogues could also efficiently catalyze the asymmetric hydrogenation of quinolines in undegassed solvent. Asymmetric tandem reduction of various 2-(aroylmethyl)quinolines was achieved in high yield with excellent enantioselectivity and good diastereoselectivity. More challenging substrates, alkyl- and aryl-substituted 1,5- and 1,8-naphthyridine derivatives were successfully hydrogenated with these chiral ruthenium catalysts to give 1,2,3,4-tetrahydronaphthyridines with good to excellent enantioselectivity. Unlike the asymmetric hydrogenation of ketones, quinoline is reduced via a stepwise H+ /H- transfer process outside the coordination sphere rather than a concerted mechanism. The enantioselectivity originates from the CH/pi attraction between the eta6 -arene ligand in the Ru-complex and the fused phenyl ring of dihydroquinoline via a 10-membered ring transition state with the participation of TfO- anion. In addition, the Ru-catalyzed asymmetric hydrogenation of quinolines could be carried out in some environmentally benign reaction media, such as undegassed water, RTILs and oligo(ethylene glycol)s (OEGs). In the latter two cases, unique chemoselectivity and/or reactivity were observed. Catalyst recycling could also be realized by using [BMIM]PF6 and OEGs as solvents, as well as via magnetic nanoparticles. Applications of this catalytic protocol were also exemplified by the employments of the reduced products for the syntheses of some important natural alkaloids, pharmaceutical intermediates, as well as chiral diamine ligands. PMID- 27555531 TI - Sorbent track: Quantitative monitoring of adsorbed VOCs under in-situ plasma exposure. AB - Sorbent-TRACK is a new device developed to monitor adsorption and surface oxidation of pollutants under direct plasma exposure. It is based on direct transmitted Fourier Transformed Infrared (FTIR) spectroscopy. A pyrex reactor under controlled gas pressure and composition is inserted on the infrared beam of a commercially available Nicolet 5700 FTIR spectrometer. A substrate holder is located on the optical path of the infrared beam. A thin pellet of a dedicated catalyst (CeO2 in the present work) is inserted in a substrate holder and can be exposed to direct plasma treatment using a Dielectric Barrier Discharge. The time resolution of Sorbent-TRACK is limited by the time resolution of the Nicolet 5700 FTIR spectrometer and close to 30 s. The dynamic of the adsorption and plasma oxidation of acetone and isopropanol on CeO2 are studied and intermediates are monitored. Performances and sensitivity of Sorbent-TRACK are reported Adsorption and oxidation of acetone leads to production of adsorbed isobutene and acetic acid, where oxidation of isopropanol gives mainly to adsorbed acetone, mesityl oxide and acetate. An increase of the plasma power leads to an increase of the isopropanol and acetone oxidation rate and a related increase of the production of adsorbed intermediates. PMID- 27555532 TI - Measurements of dermal uptake of nicotine directly from air and clothing. AB - In this preliminary study, we have investigated whether dermal uptake of nicotine directly from air or indirectly from clothing can be a meaningful exposure pathway. Two participants wearing only shorts and a third participant wearing clean cotton clothes were exposed to environmental tobacco smoke (ETS), generated by mechanically "smoking" cigarettes, for three hours in a chamber while breathing clean air from head-enveloping hoods. The average nicotine concentration (420 MUg/m3 ) was comparable to the highest levels reported for smoking sections of pubs. Urine samples were collected immediately before exposure and 60 hour post-exposure for bare-skinned participants. For the clothed participant, post-exposure urine samples were collected for 24 hour. This participant then entered the chamber for another three-hour exposure wearing a hood and clothes, including a shirt that had been exposed for five days to elevated nicotine levels. The urine samples were analyzed for nicotine and two metabolites-cotinine and 3OH-cotinine. Peak urinary cotinine and 3OH-cotinine concentrations for the bare-skinned participants were comparable to levels measured among non-smokers in hospitality environments before smoking bans. The amount of dermally absorbed nicotine for each bare-skinned participant was conservatively estimated at 570 MUg, but may have been larger. For the participant wearing clean clothes, uptake was ~20 MUg, and while wearing a shirt previously exposed to nicotine, uptake was ~80 MUg. This study demonstrates meaningful dermal uptake of nicotine directly from air or from nicotine-exposed clothes. The findings are especially relevant for children in homes with smoking or vaping. PMID- 27555533 TI - Allogeneic Hematopoietic Stem Cell Transplantation in Thirty-Four Pediatric Cases of Mucopolysaccharidosis-A Ten-Year Report from the China Children Transplant Group. AB - We investigated the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric patients with mucopolysaccharidosis (MPS). A retrospective analysis of transplantation data from 34 cases of MPS from the China Children Transplant Group, treated between December 2004 and September 2015, was conducted. Among the 34 cases, 12 cases were type I, 12 were type II, 4 were type IV, 4 were type VI, and 2 were of an unknown type. The median age at transplantation was 3.75 years (range, 1 to 7 years); the median follow-up time was 14 months (range, 2 to 119 months). Eleven patients underwent unrelated cord blood transplantation and 23 underwent peripheral blood stem cell transplantation (4 cases with an HLA-matched sibling donor, 2 cases with an HLA-mismatched related donor, and 17 cases with an unrelated donor). A busulfan-based myeloablative regimen was used as a conditioning regimen. The estimated overall survival at 3 years was 84.8% +/- 6.3% and 91.2% of the patients (31 of 34) achieved full donor chimerism. Twenty-seven children were evaluable and all but 1 (carrier sibling donor; enzyme level improved but failed to reach normal) achieved normal enzyme level after transplantation. The incidence of grades II to IV acute graft-versus-host disease (aGVHD) was 41.1% (14 of 34), wherein the incidence of grades III and IV aGVHD was 11.8% (4 of 34). The incidence of moderate-to-severe chronic graft-versus-host disease was 5.9% (2 of 34). There was a significant difference in the survival rate between children who received transplantation before 2009 and those after 2009 (55.6% versus 95.7%, P = .002); the survival rate was lower in patients with pneumonia before transplantation than in those with no active infection before transplantation (66.7% versus 95.5%, P = .019), and no significant differences in survival rates were observed among children with different disease types, ages at transplantation, donor/graft source, and conditioning regimens. After transplantation, upper-airway obstruction, hepatosplenomegaly, and corneal clouding were significantly improved; hearing and motor function were improved to a certain extent; valvular heart disease was improved in some patients but progressed in others; and short stature and speech skills showed little improvement. AlloHSCT may save the lives of patients with MPS I, II, IV or VI and could improve quality of life. Pretransplantation pneumonia affects transplantation outcomes. Advances in transplantation protocols and techniques help to improve patient prognosis. Well matched unrelated donors can also be an ideal donor source. Standardized follow up and a multidisciplinary team contribute to accurate evaluation of long-term post-transplantation outcome and further improve the quality of life of MPS patients. PMID- 27555534 TI - Neural substrates of a schizotypal spectrum in typically-developing children: Further evidence of a normal-pathological continuum. AB - Schizophrenia represents the extreme end of a distribution of traits that extends well into the general population. Using a recently developed measure of psychotic like traits in children, we examined the neural substrates of psychotic (and other psychiatric) symptoms using structural magnetic resonance imaging (MRI). Twenty-eight typically-developing children (14 males) between the ages of 6-17 years underwent a 3T MRI scan. Parents completed the Psychiatric and Schizotypal Inventory for Children. Results revealed that caudate, amygdala, hippocampal and middle temporal gyrus volumes were associated with quantitative dimensions of psychiatric traits. Furthermore, results suggest a differential a sexually dimorphic pattern of brain-schizotypy associations. These findings highlight brain-behavior continuities between clinical conditions such as schizophrenia and normal trait variation in typical development. PMID- 27555535 TI - IL-7 and Depression: The importance of gender and blood fraction. AB - Interleukin 7 (IL-7) is involved in B and T cell development and differentiation. Recent work suggests IL-7 may be altered in depression; however, we have previously shown that gender and blood fraction oftentimes impacts putative biomarker relationships among those with and without Alzheimer's disease (AD). The current study examined the impact of blood fraction (serum versus plasma) and gender on the IL7 depression link in a sample of elders with and without AD. Non fasting serum (150 AD cases 150 controls) and plasma (100 AD cases, 100 controls) IL-7 levels were assayed via electrochemiluminescence. The correlation between serum and plasma for IL-7 was 0.34. In the total sample, serum (r(2)=0.16, p=0.006) and plasma (r(2)=-0.20, p=0.007) IL-7 levels were significantly, but inversely, correlated with GDS-30 scores. When split by gender, serum IL-7 levels were significantly positively associated with GDS scores among men (r(2)=0.34, p=0.001) whereas plasma IL-7 levels (r(2)=-0.23, p=0.008) were significantly negatively associated with GDS scores among women. A logistic regression model predicting depression status (GDS30>=10) included age, gender, education, plasma, and serum IL-7 levels, found both significantly associated with depression status, but in opposite directions. Our findings support a significant link between IL-7 and depression; however, we further highlight the importance of blood fraction and gender when examining this relationship. Additionally, these findings further support the need for additional work that could lead to targeted therapeutic interventions utilizing anti-inflammatory medications for individuals with depression. PMID- 27555536 TI - Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function. AB - Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100MUg/kg/side) and H-89(10MUM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative related neurodegenerative disorders. PMID- 27555537 TI - TRPM7 functions in non-neuronal and neuronal systems: Perspectives on its role in the adult brain. AB - Transient receptor potential melastatin-like 7 (TRPM7) has a unique dual protein structure. It is an ion channel that has biophysical characteristics enabling divalent cations transport and a kinase domain involved in molecular events starting from modulating signaling pathways to inducing chromatin remodeling. Over the past 15 years, significant progress in the molecular and functional characterization of TRPM7 has been made in peripheral tissue and/or cell lines. TRPM7 appears to be involved in a plethora of physiological and pathological processes including embryonic development, organogenesis, cell proliferation and survival, and cell death following certain triggers. In the post-mitotic neuronal cells, however, the functional role of TRPM7 remains unclear. Majority of the progress in this area of research has focused on the potential role of TRPM7 in mediating neuronal death following ischemia-like and neuronal injuries-like conditions. Here, we summarize major progress on the biological roles of the TRPM7 during development and in mitotic systems (cell lines). Then, we address the recent developments made in neuronal systems. Besides its role in neuronal death, we emphasize on direct and indirect evidences that could link TRPM7 to fundamental neurobiological processes such as synaptic transmission, synapse remodeling, plasticity, cognitive functions as well as to some mental disorders. Therefore, we propose that an equivalent effort is demanded to systematically characterize the role of TRPM7 in healthy neural system before presenting it as a potential molecular target to treat neurodegenerative disorders or to prevent neuronal death following ischemia and/or neuronal injuries. PMID- 27555538 TI - Linking blast physics to biological outcomes in mild traumatic brain injury: Narrative review and preliminary report of an open-field blast model. AB - Blast exposures are associated with traumatic brain injury (TBI) and blast induced TBIs are common injuries affecting military personnel. Department of Defense and Veterans Administration (DoD/VA) reports for TBI indicated that the vast majority (82.3%) has been mild TBI (mTBI)/concussion. mTBI and associated posttraumatic stress disorders (PTSD) have been called "the invisible injury" of the current conflicts in Iraq and Afghanistan. These injuries induce varying degrees of neuropathological alterations and, in some cases, chronic cognitive, behavioral and neurological disorders. Appropriate animal models of blast-induced TBI will not only assist the understanding of physical characteristics of the blast, but also help to address the potential mechanisms. This report provides a brief overview of physical principles of blast, injury mechanisms related to blast exposure, current blast animal models, and the neurological behavioral and neuropathological findings related to blast injury in experimental settings. We describe relationships between blast peak pressures and the observed injuries. We also report preliminary use of a highly reproducible and intensity-graded blast murine model carried out in open-field with explosives, and describe physical and pathological findings in this experimental model. Our results indicate close relationships between blast intensities and neuropathology and behavioral deficits, particularly at low level blast intensities relevant to mTBI. PMID- 27555539 TI - Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats. AB - Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40-50% in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals. PMID- 27555540 TI - Combat blast related traumatic brain injury (TBI): Decade of recognition; promise of progress. AB - Between April 2007 and December 2015, the Veterans Health Administration (VHA) screened one million combat veterans for traumatic brain injury (TBI), among 2.6 million deployed during operations Enduring Freedom, Iraqi Freedom and New Dawn (OEF/OIF/OND). Since 2007, among those reporting, screened and referred for definitive evaluation, approximately 8.4% of these Veterans received a diagnosis of TBI, the majority characterized as mTBI/Concussion (mTBI) and, in great proportion, related to blast exposures. Mild Traumatic brain injury called "a signature injury" is also known as 'the invisible injury' of these conflicts. Identifying and assessing neuropathological, cellular and resulting cognitive, emotional, behavioral and neurological consequences of mTBI comprise vast clinical and research challenges. We provide a brief overview of current history, injury mechanisms related to blast exposure, coordinated research support, and the need to understand specific cellular and neurological changes occurring with blast injury, particularly mTBI. PMID- 27555541 TI - Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress. AB - Sarcosine, an N-methyl-d-aspartate receptor enhancer, can improve depression-like behavior in rodent models and depression in humans. We found that a single dose of sarcosine exerted antidepressant-like effects with rapid concomitant increases in the mammalian target of rapamycin (mTOR) signaling pathway activation and enhancement of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) membrane insertion. Sarcosine may play a crucial role in developing novel therapy for depression. For a detailed understanding of sarcosine, this study examined the effects of long-term sarcosine treatment on the forced swim test (FST), mTOR signaling, and AMPAR membrane insertion in rats. The effects of long term sarcosine treatment were examined in naive rats and rats exposed to chronic unpredictable stress (CUS). Long-term sarcosine treatment (560mg/kg/d for 21 d) significantly ameliorated the increased immobility induced by CUS in the FST, reaffirming the potential role of sarcosine as an antidepressant for depressed patients. The same long-term treatment exhibited no such effect in naive rats despite increased mTOR activation and AMPAR membrane insertion in both groups. Our findings clearly show CUS-exposed rats are sensitive to long-term sarcosine treatment in FST and the response at the same dose is absent in naive rats. Nevertheless, the distinct sensitivity to long-term sarcosine treatment in rats with or without CUS is not associated with the activated mTOR signaling pathway or increased AMPAR membrane insertion. Additionally, understanding the behavioral and molecular basis of distinct responses is vital important for developing personalized treatment programs to increase the probability of success when treating depression. PMID- 27555543 TI - Concordance between HER-2 status determined by qPCR in Fine Needle Aspiration Cytology (FNAC) samples compared with IHC and FISH in Core Needle Biopsy (CNB) or surgical specimens in breast cancer patients. AB - Determining the status of HER2-neu amplification and overexpression in breast cancer is crucial for prognosis but mostly for treatment purposes. Standard techniques include the determination of IHC in combination with in situ hybridization techniques to confirm a HER2-neu amplification in case of IHC2+ using either a core-needle biopsy or a surgical specimen. qPCR has been also demonstrated to be able to determine HER2 status, mostly in core biopsies or in surgical specimens. Fine-needle aspiration is a reliable, quicker and less invasive technique that is widely used for diagnosis of invasive breast cancer. In this study, we assessed the performance of qPCR in invasive breast carcinomas to determine HER2-neu status by using fine-needle aspiration samples and comparing to standard IHC and FISH. From a total of 154 samples from patients who had nodular breast lesions and attended the 1-day-stop clinic at the Gustave Roussy from March 2013 to October 2014, qPCR was able to determine the HER2 status in a mean of 3.7 days (SD 3.1). The overall concordance with standard HER2 testing was very high: 97% (95% CI 0.94 to 0.99); sensitivity was 96% (0.87-1), specificity 98% (0.95-1) and positive and negative predictive values 88% (0.75-1) and 99% (0.98-1), respectively. In conclusion, our study demonstrates that qPCR performed using fine-needle aspiration samples from a primary tumour is a reliable and fast method to determine HER2/neu status in patients with early breast cancer. PMID- 27555542 TI - A large-scale analysis of alternative splicing reveals a key role of QKI in lung cancer. AB - Increasing interest has been devoted in recent years to the understanding of alternative splicing in cancer. In this study, we performed a genome-wide analysis to identify cancer-associated splice variants in non-small cell lung cancer. We discovered and validated novel differences in the splicing of genes known to be relevant to lung cancer biology, such as NFIB, ENAH or SPAG9. Gene enrichment analyses revealed an important contribution of alternative splicing to cancer-related molecular functions, especially those involved in cytoskeletal dynamics. Interestingly, a substantial fraction of the altered genes found in our analysis were targets of the protein quaking (QKI), pointing to this factor as one of the most relevant regulators of alternative splicing in non-small cell lung cancer. We also found that ESYT2, one of the QKI targets, is involved in cytoskeletal organization. ESYT2-short variant inhibition in lung cancer cells resulted in a cortical distribution of actin whereas inhibition of the long variant caused an increase of endocytosis, suggesting that the cancer-associated splicing pattern of ESYT2 has a profound impact in the biology of cancer cells. Finally, we show that low nuclear QKI expression in non-small cell lung cancer is an independent prognostic factor for disease-free survival (HR = 2.47; 95% CI = 1.11-5.46, P = 0.026). In conclusion, we identified several splicing variants with functional relevance in lung cancer largely regulated by the splicing factor QKI, a tumor suppressor associated with prognosis in lung cancer. PMID- 27555544 TI - OsFRDL1 expressed in nodes is required for distribution of iron to grains in rice. AB - Iron (Fe) is essential for plant growth and development, but the molecular mechanisms underlying its distribution to different organs are poorly understood. We found that OsFRDL1 (FERRIC REDUCTASE DEFECTIVE LIKE 1), a plasma membrane localized transporter for citrate, was highly expressed in the upper nodes of rice at the reproductive growth stage. OsFRDL1 was expressed in most cells of enlarged vascular bundles, diffuse vascular bundles, and the interjacent parenchyma cell bridges of uppermost node I, as well as vascular tissues of the leaf blade, leaf sheath, peduncle, rachis, husk, and stamen. Knockout of OsFRDL1 decreased pollen viability and grain fertility when grown in a paddy field. Iron was deposited in the parenchyma cell bridges, a few of the cell layers of the parenchyma tissues outside of the bundle sheath of enlarged vascular bundles in node I in both the wild-type rice and osfrdl1 mutant, but the mutant accumulated more Fe than the wild-type rice in this area. A stem-fed experiment with stable isotope 57Fe showed that the distribution of Fe in the anther and panicle decreased in the knockout line, but that in the flag leaf it increased compared with the wild-type rice. Taken together, our results show that OsFRDL1 expressed in the upper nodes is required for the distribution of Fe in the panicles through solubilizing Fe deposited in the apoplastic part of nodes in rice. PMID- 27555545 TI - Aggregation Induced Emission Fluorogens Based Nanotheranostics for Targeted and Imaging-Guided Chemo-Photothermal Combination Therapy. AB - Nanotheranostics for biomedical imaging-guided cancer therapy have attracted increasing interest due to their capabilities of both precise tumor diagnosis and high therapeutic efficacy. Among the diverse imaging models, fluorescence imaging have been extensively researched for their high sensitivity, simple operation, and low cost. In this work, aggregation induced emission (AIE) fluorogens based targeted nanotheranostics are facilely fabricated via paclitaxel (PTX) induced assembly of proteins for the first time. Thanks to the unique fluorescence property of AIE fluorogens PhENH2 , the prepared theranostic nanoplatforms can emit bright fluorescence even after being incorporated with the photothermal therapy agent polypyrrole (PPy), which will often decrease or quench the emission of common fluorescence dyes. The target moiety of cyclic arginine-glycine aspartic acid (cRGD) endows the nanotheranostics with outstanding targeting ability, which can further facilitate the targeted imaging and cancer treatment. As revealed by the in vitro and in vivo experiments, the prepared nanotheranostics human serum albumin-PhENH2 -PPy-PTX-cRGD shows impressive performance in the targeted fluorescence imaging even after intravenous injection for 48 h, and their combined chemo-photothermal therapy is also very effective. These results indicate that AIE fluorogens based nanotheranostics would find a promising prospect in further improved multimodal imaging and imaging guided cancer treatment. PMID- 27555546 TI - CT-guided Cervical Bone Biopsy in 43 Patients: Diagnostic Yield and Safety at Two Large Tertiary Care Hospitals. AB - RATIONALE AND OBJECTIVES: The cervical spine is a high-risk area for percutaneous biopsy compared to the thoracic and lumbar regions. Biopsy of the cervical spine is less commonly undertaken, and previously published series on diagnostic yield and safety of cervical spine biopsy have been limited to 12 patients or less. The purpose of our study is to further define the diagnostic yield of computed tomography (CT)-guided biopsy for bony lesions identified in the cervical spine, by combining data from two large tertiary care referral centers. METHODS: A retrospective review of an imaging database was performed to identify all percutaneous CT-guided biopsies of the cervical spine performed at two tertiary care hospitals from 2010 to 2015. Core biopsies were obtained whenever possible and supplemented with fine-needle aspiration in some cases. Histopathologic results of the biopsy were recorded, as were changes in subsequent management, need for repeat biopsy, and complications. RESULTS: Forty-three patients underwent CT-guided biopsy of the cervical spine. Sufficient tissue for histopathologic analysis was obtained in 41 out of 43 cases, for a yield of 95%. One case was false-negative and one was deemed insufficient by the pathologist for diagnostic purposes; in both of these cases, only a fine-needle aspiration was obtained. There were no immediate or delayed complications. CONCLUSIONS: Percutaneous biopsy of the cervical spine is a safe and high-yield method of obtaining a tissue diagnosis when performed under image guidance with CT. PMID- 27555547 TI - Social Capital and Unretirement: Exploring the Bonding, Bridging, and Linking Aspects of Social Relationships. AB - Working longer is an important area of research given extended life expectancy, shortfalls of retirement income, desires to remain socially engaged, and solvency concerns of social insurance programs. The purpose of this longitudinal population-based study of older adults is to examine how different types of social resources (social bonding, bridging, and linking) relate to returning to work after retirement. Data were drawn from the Health and Retirement Study of fully retired older adults aged 62+ in 1998 ( N = 8,334) and followed to 2008. After controlling for a comprehensive set of fixed and time-varying covariates, findings suggest that social bridging (informal volunteering) and social linking (formal volunteering, partnered with an employed spouse) were strongly and positively related to returning to work (Hazard Ratio [HR]: 1.49, p < .001; HR: 1.58, p < .0001; and HR: 1.75, p < .0001, respectively). Social bonding resources were not significantly associated with returning to work. Implications for social policy are discussed. PMID- 27555548 TI - Transient glutathione depletion in the substantia nigra compacta is associated with neuroinflammation in rats. AB - Glutathione (GSH) deficiency has been identified as an early event in the progression of Parkinson's disease. However, the role of GSH in the etiology and pathogenesis of this neurodegenerative disorder is not well established. The aim of this study is to assess the effect of transient GSH depletion in the substantia nigra pars compacta (SNpc) on neuroinflammation after the injection of a single dose of l-buthionine sulfoximine (BSO) into the SNpc of male Sprague Dawley rats. The results showed that BSO treatment stimulates microglia (p<0.01) and astroglial response (p<0.01), c-Jun N-terminal kinase and inducible nitric oxide synthase (iNOS) (p<0.001) in the SNpc, accompanied by dopaminergic dysfunction. In addition, high levels of tumor necrosis factor alpha (p<0.01), interleukins IL-1beta p<0.01), IL-6 p<0.001) and nitric oxide p<0.01) were found in the treated animals compared to control groups, while no significant differences were found in IL-10 levels. These results suggest that transient GSH depletion can increase the susceptibility of SNpc to degeneration by promoting an inflammatory response and nitrosative stress, reinforcing the possible role of GSH unbalance, oxygen/nitrogen reactive species and neuroinflammation as causal factors on the degeneration of the SNpc. PMID- 27555549 TI - Short-term Internet-search practicing modulates brain activity during recollection. AB - Internet-searching behaviors may change ways in which we find, store and consider information. In this study, we tested the effect of short-term Internet-search practicing on recollection processes. Fifty-nine human subjects with valid data (Experimental group, 43; Control group, 16) completed procedures involving a pre test, 6days of practicing, and a post-test. Behavioral and imaging results were obtained and within- and between-group comparisons were made at pre-test and post test times. With respect to behavioral performance, six days of practicing was associated with improved behavioral performance during Internet searching: subjects in the experimental group showed shorter response times (RTs) and similar accuracy rates during recollection at post-test as compared to pre-test. During imaging and as compared to pre-test data, subjects in the experimental group showed during post-test recall relatively decreased brain activations bilaterally in the middle frontal and temporal gyri. Such findings were not observed in the control group. The findings suggest that six days of practicing Internet searching may improve the efficiency of Internet searching without influencing the accuracy of recollection, with neuroimaging results implicating cortical regions involved in long-term memory and executive processing. PMID- 27555550 TI - Rat odontoblasts may use glutamate to signal dentin injury. AB - Accumulating evidence indicates that odontoblasts act as sensor cells, capable of triggering action potentials in adjacent pulpal nociceptive axons, suggesting a paracrine signaling via a currently unknown mediator. Since glutamate can mediate signaling by non-neuronal cells, and peripheral axons may express glutamate receptors (GluR), we hypothesized that the expression of high levels of glutamate, and of sensory receptors in odontoblasts, combined with an expression of GluR in adjacent pulpal axons, is the morphological basis for odontoblastic sensory signaling. To test this hypothesis, we investigated the expression of glutamate, the thermo- and mechanosensitive ion channels transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and TWIK-1-related K+channel (TREK-1), and the glutamate receptor mGluR5, in a normal rat dental pulp, and following dentin injury. We also examined the glutamate release from odontoblast in cell culture. Odontoblasts were enriched with glutamate, at the level as high as in adjacent pulpal axons, and showed immunoreactivity for TRPV1, TRPA1, and TREK-1. Pulpal sensory axons adjacent to odontoblasts expressed mGluR5. Both the levels of glutamate in odontoblasts, and the expression of mGluR5 in nearby axons, were upregulated following dentin injury. The extracellular glutamate concentration was increased significantly after treating of odontoblast cell line with calcium permeable ionophore, suggesting glutamate release from odontoblasts. These findings lend morphological support to the hypothesis that odontoblasts contain glutamate as a potential neuroactive substance that may activate adjacent pulpal axons, and thus contribute to dental pain and hypersensitivity. PMID- 27555551 TI - Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia reperfusion injury in rats - A possible new hydrogen resource for clinical use. AB - Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. PMID- 27555552 TI - Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia ischemia. AB - Males are more susceptible than females to long-term cognitive deficits following neonatal hypoxic-ischemic encephalopathy (HIE). Mitochondrial dysfunction is implicated in the pathophysiology of cerebral hypoxia-ischemia (HI), but the influence of sex on mitochondrial quality control (MQC) after HI is unknown. Therefore, we tested the hypothesis that mitophagy is sexually dimorphic and neuroprotective 20-24h following the Rice-Vannucci model of rat neonatal HI at postnatal day 7 (PN7). Mitochondrial and lysosomal morphology and degree of co localization were determined by immunofluorescence in the cerebral cortex. No difference in mitochondrial abundance was detected in the cortex after HI. However, net mitochondrial fission increased in both hemispheres of female brain, but was most extensive in the ipsilateral hemisphere of male brain following HI. Basal autophagy, assessed by immunoblot for the autophagosome marker LC3BI/II, was greater in males suggesting less intrinsic reserve capacity for autophagy following HI. Autophagosome formation, lysosome size, and TOM20/LAMP2 co localization were increased in the contralateral hemisphere following HI in female, but not male brain. An accumulation of ubiquitinated mitochondrial protein was observed in male, but not female brain following HI. Moreover, neuronal cell death with NeuN/TUNEL co-staining occurred in both hemispheres of male brain, but only in the ipsilateral hemisphere of female brain after HI. In summary, mitophagy induction and neuronal cell death are sex dependent following HI. The deficit in elimination of damaged/dysfunctional mitochondria in the male brain following HI may contribute to male vulnerability to neuronal death and long-term neurobehavioral deficits following HIE. PMID- 27555554 TI - Innovative Strength-Based Care in Child and Adolescent Inpatient Psychiatry. AB - PROBLEM: Child and adolescent psychiatric units serve the highest risk, most vulnerable populations in the mental health delivery system. This article describes the integration of a strength-based approach with a traditional, medical model of psychiatric care on an acute inpatient unit. A strength-based framework allows for increased focus on exploring patients' goals, strengths, relationships, skills, and family communication within the hospital setting. METHODS: The process of integration of strength-based care is described, followed by discussion of the implementation and evaluation of interventions, including mindfulness, family movie, narrative, and animal-assisted therapies. FINDINGS: Innovative interventions led to improvement in patient symptoms, unit culture, and patient, family, and staff satisfaction. CONCLUSION: A strong emphasis on strength-based, multidisciplinary treatment has enhanced patient care, as the goals of acute inpatient admission are broadened to include more than diagnosis and medication management. PMID- 27555553 TI - Distribution patterns of phthalic acid esters in soil particle-size fractions determine biouptake in soil-cereal crop systems. AB - The use of wastewater irrigation for food crops can lead to presence of bioavailable phthalic acid esters (PAEs) in soils, which increase the potential for human exposure and adverse carcinogenic and non-cancer health effects. This study presents the first investigation of the occurrence and distribution of PAEs in a maize-wheat double-cropping system in a wastewater-irrigated area in the North China Plain. PAE levels in maize and wheat were found to be mainly attributed to PAE stores in soil coarse (250-2000 MUm) and fine sand (53-250 MUm) fractions. Soil particle-size fractions with higher bioavailability (i.e., coarse and fine sands) showed greater influence on PAE congener bioconcentration factors compared to PAE molecular structures for both maize and wheat tissues. More PAEs were allocated to maize and wheat grains with increased soil PAE storages from wastewater irrigation. Additional findings showed that levels of both non-cancer and carcinogenic risk for PAE congeners in wheat were higher than those in maize, suggesting that wheat food security should be prioritized. In conclusion, increased soil PAE concentrations specifically in maize and wheat grains indicate that wastewater irrigation can pose a contamination threat to food resources. PMID- 27555556 TI - Contradictory views of nursing care among students at the end of their nursing education. AB - AIM: To understand how nursing students at the end of their nursing education view nursing care. BACKGROUND: Although care is understood as the essence of nursing, it is often difficult for nurses to provide care, which demonstrates a contradiction between theory and practice. Moreover, it is unknown to what extent this contradiction is transmitted to future nursing professionals or how they view nursing care and its practice. DESIGN: Qualitative ethnographic research. METHODS: The fieldwork was conducted between December 2010 - May 2012 in a university nursing school in Barcelona and two centres where students carry out most of their practical education. The data collection techniques were participant observation and focus groups. A thematic analysis was used. RESULTS: The students demonstrated contradictory views of nursing care. On one hand, they voiced a more theoretical, official definition where care is considered the core of the profession. On the other hand, they also expressed a view where the provision of care is not nurses' principal daily activity, a fact that did not surprise them. Students interpreted caring as an activity that has low value and that can be transferred unproblematically to other professionals. CONCLUSION: The contradictory views of care reveal a problem in the transmission of the definition of nursing to new generations of professionals and reflect a problematic professional reality where there is dissonance between how nursing is defined and how it is carried out in practice. PMID- 27555557 TI - Cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability. AB - We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants ( N = 474) were divided into four groups based on IQ and severity of alcohol use-related problems. IQ was estimated using (a short form of) the Wechsler Adult Intelligence Scale third edition. Severity of alcohol use-related problems was assessed using the Alcohol Use Disorder Identification Test. Overall, there were no significant differences between light and problematic drinkers on estimated VIQ. Within the group without MBID, estimated PIQ was significantly lower. Estimated PIQ was not lower in problematic drinkers with MBID compared to light drinkers with MBID. The results are indicative of cognitive deficits in problematic drinkers without MBID. Screening for cognitive deficits with additional instruments is advised. PMID- 27555555 TI - Eliminating Nox2 reactive oxygen species production protects dystrophic skeletal muscle from pathological calcium influx assessed in vivo by manganese-enhanced magnetic resonance imaging. AB - KEY POINTS: Inhibiting Nox2 reactive oxygen species (ROS) production reduced in vivo calcium influx in dystrophic muscle. The lack of Nox2 ROS production protected against decreased in vivo muscle function in dystrophic mice. Manganese enhanced magnetic resonance imaging (MEMRI) was able to detect alterations in basal calcium levels in skeletal muscle and differentiate disease status. Administration of Mn2+ did not affect muscle function or the health of the animal, and Mn2+ was cleared from skeletal muscle rapidly. We conclude that MEMRI may be a viable, non-invasive technique to monitor molecular alterations in disease progression and evaluate the effectiveness of potential therapies for Duchenne muscular dystrophy. ABSTRACT: Duchenne muscular dystrophy (DMD) is an X linked progressive degenerative disease resulting from a mutation in the gene that encodes dystrophin, leading to decreased muscle mechanical stability and force production. Increased Nox2 reactive oxygen species (ROS) production and sarcolemmal Ca2+ influx are early indicators of disease pathology, and eliminating Nox2 ROS production reduces aberrant Ca2+ influx in young mdx mice, a model of DMD. Various imaging modalities have been used to study dystrophic muscle in vivo; however, they are based upon alterations in muscle morphology or inflammation. Manganese has been used for indirect monitoring of calcium influx across the sarcolemma and may allow detection of molecular alterations in disease progression in vivo using manganese-enhanced magnetic resonance imaging (MEMRI). Therefore, we hypothesized that eliminating Nox2 ROS production would decrease calcium influx in adult mdx mice and that MEMRI would be able to monitor and differentiate disease status in dystrophic muscle. Both in vitro and in vivo data demonstrate that eliminating Nox2 ROS protected against aberrant Ca2+ influx and improved muscle function in dystrophic muscle. MEMRI was able to differentiate between different pathological states in vivo, with no long-term effects on animal health or muscle function. We conclude that MEMRI is a viable, non invasive technique to differentiate disease status and might provide a means to monitor and evaluate the effectiveness of potential therapies in dystrophic muscle. PMID- 27555558 TI - Mycological profile of tinea capitis in schoolchildren in rural southern Ethiopia. AB - Tinea capitis is a known common infection among schoolchildren in developing countries that is still underreported in Ethiopia. The aim of this study was to examine the epidemiologic and etiologic profile of tinea capitis among school aged children in a rural area in southern Ethiopia. We collected demographic and clinicodermatological data from school children aged 3-12 years with tinea infections. Pathologic specimens were taken for potassium hydroxide (KOH) mount and mycological culture. Dermatophyte species were identified by macroscopic examination of the colony and microscopic examination of fungal cultures. A total of 634 schoolchildren were screened in the study; 128 cases were suspected for tinea capitis based on clinical examination of which 99 patients (mean age 6.7 years within a range of 4-12 years), who were subsequently positive, either based on KOH examination or showed growth of dermatophytes on culture, were included in our study. The ratio of males to females was 3:1. A total of 88 patients (89.9%) had a culture positive for dermatophytes. The zoophilic species Trichophyton verrucosum was the most prevalent isolate (n = 29 cases), followed by the anthropophilic species T. tonsurans (n = 27). The other Trichophyton species implicated were T. mentagrophytes (n = 14), as well as T. schoenleinii, T. soudanense, and T. violaceum. Only 11 of the isolates belonged to the genus Microsporum: M. audouinii (n = 8), M. ferrugineum (n = 2), and M. gallinae (n = 1). T. verrucosum, followed by T. tonsurans were the most frequent causative agents in this study. PMID- 27555559 TI - Different classes of hydrolytic enzymes produced by multidrug-resistant yeasts comprising the Candida haemulonii complex. AB - The production of enzymes in clinical isolates of Candida haemulonii (Ch, n = 5), Candida duobushaemulonii (Cd, n = 4) and Candida haemulonii var. vulnera (Chv, n = 3) was identified by agar plate. Aspartic protease, phytase, caseinolytic and hemolytic activities were detected in all the isolates. A distinct scenario was evidenced regarding the production of lipases. In this way, 80%, 50% and 100% of Ch, Cd and Chv, respectively, were phospholipase producers. Regarding esterase activity, 100%, 50% and 66.7% of Ch, Cd and Chv, respectively, were positive isolates. Esterase activity was significantly higher in isolates recovered from cutaneous candidiasis compared with those recovered from body fluids. PMID- 27555560 TI - Molecular study of the Candida parapsilosis complex in Sfax, Tunisia. AB - Candida parapsilosis, which was previously considered to be a complex of three genetically distinct groups, has emerged as a significant agent of nosocomial infections. Recently, this complex was separated into three species: C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis In Tunisia, data pertaining to these fungi are limited. Thus, the purpose of our study was to determine by BanI PCR-RFLP and ITS sequencing, the occurrence of Candida parapsilosis complex among 182 isolates identified as C. parapsilosis by phenotypical methods. C. parapsilosis sensu stricto represented 94.5% of all isolates, while C. metapsilosis and. C. orthopsilosis were identified in 3.3% and 2.2%, respectively. Sequence analysis of internal transcribed spacer region confirmed and revealed only one genotype among the C. parapsilosis sensu stricto strains, three genotypes among six C. metapsilosis strains and two genotypes among four C. orthopsilosis strains. PMID- 27555561 TI - High frequency of pathogenic Aspergillus species among nonsporulating moulds from respiratory tract samples. AB - Nonsporulating moulds (NSM) represent an identification challenge for clinical laboratories. Data on the prevalence of pathogenic species among NSM are lacking. We prospectively investigated consecutive thermotolerant (36 degrees C) clinical NSM isolates from respiratory tract samples. A total of 123 isolates were identified by DNA sequencing and phenotypically characterized. Of those, 13 (11%) were pathogenic species (Aspergillus fumigatus, n = 10; A. flavus, n = 1; A. hiratsukae, n = 1; Schizophyllum commune, n = 1). Presumptive identification of Aspergillus species among NSM can be achieved by simple phenotypic testing. PMID- 27555563 TI - A new (Ba, Ca) (Ti, Zr)O3 based multiferroic composite with large magnetoelectric effect. AB - The lead-free ferroelectric 0.5Ba(Zr0.2Ti0.8)O3 - 0.5(Ba0.7Ca0.3)TiO3 (BCZT) is a promising component for multifunctional multiferroics due to its excellent room temperature piezoelectric properties. Having a composition close to the polymorphic phase boundary between the orthorhombic and tetragonal phases, it deserves a case study for analysis of its potential for modern electronics applications. To obtain magnetoelectric coupling, the piezoelectric phase needs to be combined with a suitable magnetostrictive phase. In the current article, we report on the synthesis, dielectric, magnetic, and magnetoelectric characterization of a new magnetoelectric multiferroic composite consisting of BCZT as a piezoelectric phase and CoFe2O4 (CFO) as the magnetostrictive phase. We found that this material is multiferroic at room temperature and manifests a magnetoelectric effect larger than that of BaTiO3 -CoFe2O4 bulk composites with similar content of the ferrite phase. PMID- 27555562 TI - Spontaneous perception of numerosity in humans. AB - Humans, including infants, and many other species have a capacity for rapid, nonverbal estimation of numerosity. However, the mechanisms for number perception are still not clear; some maintain that the system calculates numerosity via density estimates-similar to those involved in texture-while others maintain that more direct, dedicated mechanisms are involved. Here we show that provided that items are not packed too densely, human subjects are far more sensitive to numerosity than to either density or area. In a two-dimensional space spanning density, area and numerosity, subjects spontaneously react with far greater sensitivity to changes in numerosity, than either area or density. Even in tasks where they were explicitly instructed to make density or area judgments, they responded spontaneously to number. We conclude, that humans extract number information, directly and spontaneously, via dedicated mechanisms. PMID- 27555564 TI - Thf1 interacts with PS I and stabilizes the PS I complex in Synechococcus sp. PCC7942. AB - Thylakoid formation1 protein (Thf1) is a multifunctional protein that is conserved in all photosynthetic organisms. In this study, we used the model cyanobacterium Synechococcus sp. PCC7942 (hereafter Synechococcus) to show that the level of Thf1 is altered in response to various stress conditions. Although this protein has been reported to be involved in thylakoid formation, the thylakoid membrane in the thf1 deletion strain (DeltaThf1) was not affected. Compared with the WT, DeltaThf1 showed reduced PS II activity, with increased levels of D1 under high light (HL) conditions, which was resulted from blocked D1 degradation by the FtsH protease and thus inhibits PS II repair. PS I was found to be more seriously affected than PS II in DeltaThf1, even under low light conditions, suggesting that PS I damage could be the primary effect of thf1 deletion in Synechococcus. Further analysis revealed that the DeltaThf1 mutant had a lower PS I subunit content and lower PS I stability under HL conditions. Further sucrose gradient fractionation of the membrane protein complexes and crosslinking and immunoblot analysis indicated that Thf1 interacts with PS I. Together, our results reveal that Thf1 interacts with PS I and thereby stabilizes PS I in Synechococcus. PMID- 27555565 TI - Excellent remission rates with limited toxicity in relapsed/refractory Langerhans cell histiocytosis with pulse dexamethasone and lenalidomide in children. AB - Refractory/relapsed Langerhans cell histiocytosis (LCH) has a difficult course with a guarded prognosis. We used a novel protocol including six cycles of pulse dexamethasone and lenalidomide in four children with LCH refractory to first-line agents and courses of cladribine and cytarabine or single-agent cladribine. All four children completed the protocol without any significant adverse effects and remain in complete and durable remission 15-18 months posttreatment. The novel protocol we propose for relapsed/refractory LCH is cost-effective and outpatient based with durable remission and minimal toxicity. This is particularly suited for resource-limited settings. PMID- 27555566 TI - Abnormal Anterior Corneal Morphology in Diabetes Observed Using In Vivo Laser scanning Confocal Microscopy. AB - PURPOSE: To assess if diabetes alters corneal epithelial, anterior stromal and subbasal nerve plexus morphology and to determine the associations between these and other clinical variables. METHODS: A cohort of 78 participants with diabetes (39 with Type 1 and 39 with Type 2 diabetes) and 29 age-matched healthy controls underwent laser-scanning confocal microscopy of the central cornea. Intermediate cell density (ICD), basal cell density (BCD), anterior stromal cell density (ASCD), corneal nerve fiber density (CNFD) and nerve fiber length (CNFL) were quantified. RESULTS: Compared with controls, participants with diabetes showed reduced ICD (6097 +/- 669 vs. 5548 +/- 669 no/mm2, P<.01), BCD (8925 +/- 1196 vs. 7842 +/- 1040 cell/mm2, P<.01), CNFD (23.4 +/- 9.1 vs. 17.5 +/- 9.7 no/mm2, P<.01) and CNFL (21.0 +/- 4.0 vs. 17.4 +/- 4.9 mm/mm2, P<.01), with no difference in ASCD (785 +/- 262 vs. 733 +/- 278 cell/mm2, respectively, P=.40). None of these structural parameters were associated with type of diabetes (P>.06). Multiple regression analysis showed that ICD and BCD were inversely associated with the diabetes duration and diastolic blood pressure (P<.05) and positively associated with CNFD (P<.01). CNFD and CNFL were inversely associated with HbA1c (P<.01), while ASCD was inversely associated with age (P<.01). CONCLUSIONS: Corneal epithelial cells and subbasal nerve fibers are reduced in patients with diabetes; however, anterior stromal cells show no difference. Furthermore, abnormalities in corneal epithelial cells and nerves are interrelated and correlated with modifiable risk factors. PMID- 27555567 TI - From air to clothing: characterizing the accumulation of semi-volatile organic compounds to fabrics in indoor environments. AB - Uptake kinetics of semi-volatile organic compounds (SVOCs) present indoors, namely phthalates and halogenated flame retardants (HFRs), were characterized for cellulose-based cotton and rayon fabrics. Cotton and rayon showed similar accumulation of gas- and particle-phase SVOCs, when normalized to planar surface area. Accumulation was 3-10 times greater by rayon than cotton, when normalized to Brunauer-Emmett-Teller (BET) specific surface area which suggests that cotton could have a longer linear uptake phase than rayon. Linear uptake rates of eight consistently detected HFRs over 56 days of 0.35-0.92 m3 /day.dm2 planar surface area and mass transfer coefficients of 1.5-3.8 m/h were statistically similar for cotton and rayon and similar to those for uptake to passive air sampling media. These results suggest air-side controlled uptake and that, on average, 2 m2 of clothing typically worn by a person would sequester the equivalent of the chemical content in 100 m3 of air per day. Distribution coefficients between fabric and air (K') ranged from 6.5 to 7.7 (log K') and were within the range of partition coefficients measured for selected phthalates as reported in the literature. The distribution coefficients were similar for low molecular weight HFRs, and up to two orders of magnitude lower than the equilibrium partition coefficients estimated using the COSMO-RS model. Based on the COSMO-RS model, time to reach 95% of equilibrium for PBDEs between fabric and gas-phase compounds ranged from 0.1 to >10 years for low to high molecular weight HFRs. PMID- 27555568 TI - Advancement in Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric Isomerization of Allylic Alcohols. AB - Catalytic asymmetric hydrogenation of ketones through the "metal-ligand cooperative mechanism" has been improved in terms of the efficiency, stereoselectivity, and scope of substrates by varying the arrangement of the catalyst structure and reaction conditions. Imino compounds are also smoothly converted to the optically active amines with appropriate catalysts. This type of catalyst exhibits excellent performance on the asymmetric isomerization of primary allylic alcohols into the optically active aldehydes. This personal account describes recent progress on these topics. PMID- 27555571 TI - Central Regulation of Glucose Metabolism in Humans: Fact or Fiction? PMID- 27555569 TI - Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice. AB - BACKGROUND: The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. METHODS: The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. RESULTS: Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. CONCLUSIONS: Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical management scenarios although the concurrent use of amiodarone requires more study. PMID- 27555572 TI - Islets Transplanted Into the Eye: Do They Improve Our Insight Into Islet Adaptation to Insulin Resistance? PMID- 27555573 TI - Orphaned No More? Glucose-Sensing Hypothalamic Neurons Control Insulin Secretion. PMID- 27555574 TI - The Muscle Race After Bariatric Surgery: Ribosomal Proteins Come First. PMID- 27555575 TI - Is There Enhanced Risk of Cerebral Ischemic Stroke by Sulfonylureas in Type 2 Diabetes? PMID- 27555576 TI - Erratum. Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells. Diabetes 2016;65:1164-1178. PMID- 27555578 TI - Comment on The Look AHEAD Research Group. Prospective Association of GLUL rs10911021 With Cardiovascular Morbidity and Mortality Among Individuals With Type 2 Diabetes: The Look AHEAD Study. Diabetes 2016;65:297-302. PMID- 27555579 TI - Response to Comment on The Look AHEAD Research Group. Prospective Association of GLUL rs10911021 With Cardiovascular Morbidity and Mortality Among Individuals With Type 2 Diabetes: The Look AHEAD Study. Diabetes 2016;65:297-302. PMID- 27555580 TI - Comment on Menke et al. Metals in Urine and Diabetes in U.S. Adults. Diabetes 2016;65:164-171. PMID- 27555581 TI - Population Genomics Reveals Low Genetic Diversity and Adaptation to Hypoxia in Snub-Nosed Monkeys. AB - Snub-nosed monkeys (genus Rhinopithecus) are a group of endangered colobines endemic to South Asia. Here, we re-sequenced the whole genomes of 38 snub-nosed monkeys representing four species within this genus. By conducting population genomic analyses, we observed a similar load of deleterious variation in snub nosed monkeys living in both smaller and larger populations and found that genomic diversity was lower than that reported in other primates. Reconstruction of Rhinopithecus evolutionary history suggested that episodes of climatic variation over the past 2 million years, associated with glacial advances and retreats and population isolation, have shaped snub-nosed monkey demography and evolution. We further identified several hypoxia-related genes under selection in R. bieti (black snub-nosed monkey), a species that exploits habitats higher than any other nonhuman primate. These results provide the first detailed and comprehensive genomic insights into genetic diversity, demography, genetic burden, and adaptation in this radiation of endangered primates. PMID- 27555582 TI - Microstructured Multilevel Bacterial Cellulose Allows the Guided Growth of Neural Stem Cells. AB - Repeated photolithographic and etching processes allow the production of multileveled polymer microstructures that can be used as templates to produce bacterial cellulose with defined surfaces on demand. By applying this approach, the bacterial cellulose surface obtains new properties and its use for culturing neural stem cells cellulose substrate topography influences the cell growth in a defined manner. PMID- 27555583 TI - The price of complexity in financial networks. AB - Financial institutions form multilayer networks by engaging in contracts with each other and by holding exposures to common assets. As a result, the default probability of one institution depends on the default probability of all of the other institutions in the network. Here, we show how small errors on the knowledge of the network of contracts can lead to large errors in the probability of systemic defaults. From the point of view of financial regulators, our findings show that the complexity of financial networks may decrease the ability to mitigate systemic risk, and thus it may increase the social cost of financial crises. PMID- 27555584 TI - Fundamental structures of dynamic social networks. AB - Social systems are in a constant state of flux, with dynamics spanning from minute-by-minute changes to patterns present on the timescale of years. Accurate models of social dynamics are important for understanding the spreading of influence or diseases, formation of friendships, and the productivity of teams. Although there has been much progress on understanding complex networks over the past decade, little is known about the regularities governing the microdynamics of social networks. Here, we explore the dynamic social network of a densely connected population of ~1,000 individuals and their interactions in the network of real-world person-to-person proximity measured via Bluetooth, as well as their telecommunication networks, online social media contacts, geolocation, and demographic data. These high-resolution data allow us to observe social groups directly, rendering community detection unnecessary. Starting from 5-min time slices, we uncover dynamic social structures expressed on multiple timescales. On the hourly timescale, we find that gatherings are fluid, with members coming and going, but organized via a stable core of individuals. Each core represents a social context. Cores exhibit a pattern of recurring meetings across weeks and months, each with varying degrees of regularity. Taken together, these findings provide a powerful simplification of the social network, where cores represent fundamental structures expressed with strong temporal and spatial regularity. Using this framework, we explore the complex interplay between social and geospatial behavior, documenting how the formation of cores is preceded by coordination behavior in the communication networks and demonstrating that social behavior can be predicted with high precision. PMID- 27555586 TI - Rich gets simpler. PMID- 27555585 TI - Hedgehog-dependent E3-ligase Midline1 regulates ubiquitin-mediated proteasomal degradation of Pax6 during visual system development. AB - Pax6 is a key transcription factor involved in eye, brain, and pancreas development. Although pax6 is expressed in the whole prospective retinal field, subsequently its expression becomes restricted to the optic cup by reciprocal transcriptional repression of pax6 and pax2 However, it remains unclear how Pax6 protein is removed from the eyestalk territory on time. Here, we report that Mid1, a member of the RBCC/TRIM E3 ligase family, which was first identified in patients with the X-chromosome-linked Opitz BBB/G (OS) syndrome, interacts with Pax6. We found that the forming eyestalk is a major domain of mid1 expression, controlled by the morphogen Sonic hedgehog (Shh). Here, Mid1 regulates the ubiquitination and proteasomal degradation of Pax6 protein. Accordantly, when Mid1 levels are knocked down, Pax6 expression is expanded and eyes are enlarged. Our findings indicate that remaining or misaddressed Pax6 protein is cleared from the eyestalk region to properly set the border between the eyestalk territory and the retina via Mid1. Thus, we identified a posttranslational mechanism, regulated by Sonic hedgehog, which is important to suppress Pax6 activity and thus breaks pax6 autoregulation at defined steps during the formation of the visual system. PMID- 27555587 TI - Cytosolic activation of cell death and stem rust resistance by cereal MLA-family CC-NLR proteins. AB - Plants possess intracellular immune receptors designated "nucleotide-binding domain and leucine-rich repeat" (NLR) proteins that translate pathogen-specific recognition into disease-resistance signaling. The wheat immune receptors Sr33 and Sr50 belong to the class of coiled-coil (CC) NLRs. They confer resistance against a broad spectrum of field isolates of Puccinia graminis f. sp. tritici, including the Ug99 lineage, and are homologs of the barley powdery mildew resistance protein MLA10. Here, we show that, similarly to MLA10, the Sr33 and Sr50 CC domains are sufficient to induce cell death in Nicotiana benthamiana Autoactive CC domains and full-length Sr33 and Sr50 proteins self-associate in planta In contrast, truncated CC domains equivalent in size to an MLA10 fragment for which a crystal structure was previously determined fail to induce cell death and do not self-associate. Mutations in the truncated region also abolish self association and cell-death signaling. Analysis of Sr33 and Sr50 CC domains fused to YFP and either nuclear localization or nuclear export signals in N benthamiana showed that cell-death induction occurs in the cytosol. In stable transgenic wheat plants, full-length Sr33 proteins targeted to the cytosol provided rust resistance, whereas nuclear-targeted Sr33 was not functional. These data are consistent with CC-mediated induction of both cell-death signaling and stem rust resistance in the cytosolic compartment, whereas previous research had suggested that MLA10-mediated cell-death and disease resistance signaling occur independently, in the cytosol and nucleus, respectively. PMID- 27555588 TI - PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front. AB - Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. Optogenetic inactivation of PLEKHG3 showed that PLEKHG3 is indispensable both for inducing and for maintaining cell polarity. By selectively binding to newly polymerized actin, PLEKHG3 promotes local Rac1/Cdc42 activation to induce more local actin polymerization, which in turn promotes the recruitment of more PLEKHG3 to induce and maintain cell front. Thus, autocatalytic reinforcement of PLEKHG3 localization to the leading edge of the cell provides a molecular basis for the proposed positive feedback loop that is required for cell polarization and directed migration. PMID- 27555589 TI - Baseplate assembly of phage Mu: Defining the conserved core components of contractile-tailed phages and related bacterial systems. AB - Contractile phage tails are powerful cell puncturing nanomachines that have been co-opted by bacteria for self-defense against both bacteria and eukaryotic cells. The tail of phage T4 has long served as the paradigm for understanding contractile tail-like systems despite its greater complexity compared with other contractile-tailed phages. Here, we present a detailed investigation of the assembly of a "simple" contractile-tailed phage baseplate, that of Escherichia coli phage Mu. By coexpressing various combinations of putative Mu baseplate proteins, we defined the required components of this baseplate and delineated its assembly pathway. We show that the Mu baseplate is constructed through the independent assembly of wedges that are organized around a central hub complex. The Mu wedges are comprised of only three protein subunits rather than the seven found in the equivalent structure in T4. Through extensive bioinformatic analyses, we found that homologs of the essential components of the Mu baseplate can be identified in the majority of contractile-tailed phages and prophages. No T4-like prophages were identified. The conserved simple baseplate components were also found in contractile tail-derived bacterial apparatuses, such as type VI secretion systems, Photorhabdus virulence cassettes, and R-type tailocins. Our work highlights the evolutionary connections and similarities in the biochemical behavior of phage Mu wedge components and the TssF and TssG proteins of the type VI secretion system. In addition, we demonstrate the importance of the Mu baseplate as a model system for understanding bacterial phage tail-derived systems. PMID- 27555591 TI - Catalytic strategy for carbon-carbon bond scission by the cytochrome P450 OleT. AB - OleT is a cytochrome P450 that catalyzes the hydrogen peroxide-dependent metabolism of Cn chain-length fatty acids to synthesize Cn-1 1-alkenes. The decarboxylation reaction provides a route for the production of drop-in hydrocarbon fuels from a renewable and abundant natural resource. This transformation is highly unusual for a P450, which typically uses an Fe(4+)-oxo intermediate known as compound I for the insertion of oxygen into organic substrates. OleT, previously shown to form compound I, catalyzes a different reaction. A large substrate kinetic isotope effect (>=8) for OleT compound I decay confirms that, like monooxygenation, alkene formation is initiated by substrate C-H bond abstraction. Rather than finalizing the reaction through rapid oxygen rebound, alkene synthesis proceeds through the formation of a reaction cycle intermediate with kinetics, optical properties, and reactivity indicative of an Fe(4+)-OH species, compound II. The direct observation of this intermediate, normally fleeting in hydroxylases, provides a rationale for the carbon-carbon scission reaction catalyzed by OleT. PMID- 27555590 TI - Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development. AB - T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 cell-driven disease and therefore is a promising target for treating autoimmune diseases. However, the molecular mechanisms controlling this balance are still unclear. Here, we report that pharmacological inhibition as well as genetic ablation of the protein kinase CK2 (CK2) ameliorates experimental autoimmune encephalomyelitis (EAE) severity and relapse incidence. Furthermore, CK2 inhibition or genetic ablation prevents TH17 cell development and promotes the generation of Treg cells. Molecularly, inhibition of CK2 leads to reduced STAT3 phosphorylation and strongly attenuated expression of the IL-23 receptor, IL-17, and GM-CSF. Thus, these results identify CK2 as a nodal point in TH17 cell development and suggest this kinase as a potential therapeutic target to treat TH17 cell-driven autoimmune responses. PMID- 27555592 TI - Vibrio cholerae biofilm growth program and architecture revealed by single-cell live imaging. AB - Biofilms are surface-associated bacterial communities that are crucial in nature and during infection. Despite extensive work to identify biofilm components and to discover how they are regulated, little is known about biofilm structure at the level of individual cells. Here, we use state-of-the-art microscopy techniques to enable live single-cell resolution imaging of a Vibrio cholerae biofilm as it develops from one single founder cell to a mature biofilm of 10,000 cells, and to discover the forces underpinning the architectural evolution. Mutagenesis, matrix labeling, and simulations demonstrate that surface adhesion mediated compression causes V. cholerae biofilms to transition from a 2D branched morphology to a dense, ordered 3D cluster. We discover that directional proliferation of rod-shaped bacteria plays a dominant role in shaping the biofilm architecture in V. cholerae biofilms, and this growth pattern is controlled by a single gene, rbmA Competition analyses reveal that the dense growth mode has the advantage of providing the biofilm with superior mechanical properties. Our single-cell technology can broadly link genes to biofilm fine structure and provides a route to assessing cell-to-cell heterogeneity in response to external stimuli. PMID- 27555593 TI - Reply to Boucher et al.: Rate and timescale of black carbon aging regulate direct radiative forcing. PMID- 27555594 TI - Jury is still out on the radiative forcing by black carbon. PMID- 27555595 TI - Rnd3 in Cancer: A Review of the Evidence for Tumor Promoter or Suppressor. AB - : Rho-GTPases are members of the Ras superfamily of small GTPases and are general modulators of important cellular processes in tumor biology such as migration and proliferation. Among these proteins, Rnd3/RhoE, an atypical Rho-GTPase devoid of GTP hydrolytic activity, has recently been studied for its putative role in tumorigenesis. Indeed, Rnd3 is implicated in processes, such as proliferation and migration, whose deregulation is linked to cancer development and metastasis. The aim of this review is to provide an overview of the data surrounding Rnd3 deregulation in cancers, its origin, and consequences. Presented here is a comprehensive account of the expression status and biological output obtained in prostate, liver, stomach, colon, lung, and brain cancers as well as in melanoma and squamous cell carcinoma. Although there appears to be no general consensus about Rnd3 expression in cancers as this protein is differently altered according to the tumor context, these alterations overwhelmingly favor a protumorigenic role. Thus, depending on the tumor type, it may behave either as a tumor suppressor or as a tumor promoter. Importantly, the deregulation of Rnd3, in most cases, is linked to patient poor outcome. IMPLICATIONS: Rnd3 has prognostic marker potential as exemplified in lung cancers and Rnd3 or Rnd3-associated signaling pathways may represent a new putative therapeutic target. Mol Cancer Res; 14(11); 1033-44. (c)2016 AACR. PMID- 27555598 TI - Secondary Victimization: Domestic Violence Survivors Navigating the Family Law System. AB - This qualitative study explored the experiences of 22 domestic violence survivors attempting to negotiate safe post-separation parenting arrangements through the Australian family law system. Their allegations of violence put them at odds with a system that values mediated settlements and shared parenting. Skeptical responses, accusations of parental alienation, and pressure to agree to unsafe arrangements exacerbated the effects of post-separation violence. Core themes in the women's narratives of engagement with the family law system-silencing, control, and undermining the mother-child relationship-mirrored domestic violence dynamics, suggesting the concept of secondary victimization as a useful lens for understanding their experiences. PMID- 27555596 TI - Predicting Sexual Assault Revictimization in a Longitudinal Sample of Women Survivors: Variation by Type of Assault. AB - This study used a large community sample of women sexual assault survivors to prospectively assess 17 theorized predictors across four types of sexual assault revictimization: unwanted contact, coercion, substance-involved assault (SIA), and force. Results indicated that predictors varied across types of revictimization: Unwanted contact and coercion appeared more common in social contexts more hostile toward survivors, whereas forcible assaults and SIAs occurred in circumstances where survivors were vulnerable to being targeted by perpetrators. Overall, the strongest predictors were social environments hostile to survivors, race, childhood sexual abuse, decreased refusal assertiveness, and having more sexual partners. We discuss implications for intervention and research. PMID- 27555597 TI - When Women Do Not Want It: Young Female Bargoers' Experiences With and Responses to Sexual Harassment in Social Drinking Contexts. AB - Women frequently experience unwanted sexual touching and persistent advances at bars and parties. This study explored women's responses to these unwanted experiences through online surveys completed by 153 female bargoers (aged 19-29) randomly recruited from a bar district. More than 75% had experienced sexual touching or persistence (46% both). Most women used multiple deterrent strategies, including evasion, facial expressions, direct refusals, aggression, friends' help, and leaving the premises. Women experienced negative feelings (disrespected, violated, disgusted, angry, embarrassed), especially from incidents involving touching. Cultural change is needed to reduce substantial negative impacts of sexual harassment on women in drinking and other settings. PMID- 27555599 TI - Tackling Trafficking by Targeting Sex Buyers: Can It Work? AB - The European legal instruments on human trafficking encourage states to tackle the demand for services of trafficked persons, for example, by making the use of services of a trafficked person a criminal offense. In Finland, buying sex from a trafficked person is a criminal offense. This article reports the results of an evaluation of the Finnish law and shows that the implementation has been inefficient. The authors argue that with an amendment of the law, the implementation could be improved but a truly efficient policy would require a total ban of sex purchase along the lines of the Swedish model. PMID- 27555600 TI - Protein RS1 (RSC1A1) Downregulates the Exocytotic Pathway of Glucose Transporter SGLT1 at Low Intracellular Glucose via Inhibition of Ornithine Decarboxylase. AB - Na+-d-glucose cotransporter 1 (SGLT1) is rate-limiting for glucose absorption in the small intestine. Shortly after intake of glucose-rich food, SGLT1 abundance in the luminal membrane of the small intestine is increased. This upregulation occurs via glucose-induced acceleration of the release of SGLT1-containing vesicles from the trans-Golgi network (TGN), which is regulated by a domain of protein RS1 (RSC1A1) named RS1-Reg. Dependent on phosphorylation, RS1-Reg blocks release of vesicles containing SGLT1 or concentrative nucleoside transporter 1. The hypothesis has been raised that RS1-Reg binds to different receptor proteins at the TGN, which trigger release of vesicles with different transporters. To identify the presumed receptor proteins, two-hybrid screening was performed. Interaction with ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme of polyamine synthesis, was observed and verified by immunoprecipitation. Binding of RS1-Reg mutants to ODC1 was characterized using surface plasmon resonance. Inhibition of ODC1 activity by RS1-Reg mutants and the ODC1 inhibitor difluoromethylornithine (DFMO) was measured in the absence and presence of glucose. In addition, short-term effects of DFMO, RS1-Reg mutants, the ODC1 product putrescine, and/or glucose on SGLT1 expressed in oocytes of Xenopus laevis were investigated. High-affinity binding of RS1-Reg to ODC1 was demonstrated, and evidence for a glucose binding site in ODC1 was provided. Binding of RS1-Reg to ODC1 inhibits the enzymatic activity at low intracellular glucose, which is blunted at high intracellular glucose. The data suggest that generation of putrescine by ODC1 at the TGN stimulates release of SGLT1 containing vesicles. This indicates a biomedically important role of ODC1 in regulation of glucose homeostasis. PMID- 27555602 TI - An Update on Travel Vaccines and Issues in Travel and International Medicine. AB - The fields of travel and international medicine are rapidly changing and growing. The role of occupational and travel health nurses is expanding and should be a focus for the future. At the American Association of Occupational Health Nurses Annual meeting on March 24, 2015, in Boston, five presentations were included in the session, An Update on Travel Vaccines and Issues in Travel and International Medicine. This article summarizes three of the presentations and includes a portion of the information generated by the Centers for Disease Control and Prevention (CDC) included in the fourth presentation. The first section focuses on the Essential Elements of Travel Medicine Programs including the pre-travel care assessment, trip research and risk identification, medication intervention review, non-pharmaceutical and prevention strategies, and post-travel care. The next section is an overview of key issues for business travelers. The growth in the number of international business travelers and unique aspects of business travel are emphasized in a comprehensive travel health program. This section also includes a discussion of expatriates and their special risks identified in recent literature (e.g., an assessment of the significant costs of health events and productivity losses by both business travelers and expatriates). The final section offers a specific example of a vaccine-preventable disease, namely, Japanese encephalitis (JE) virus, and needed changes in JE vaccine recommendations. PMID- 27555601 TI - Comparison of an Electronic Glycemic Management System Versus Provider-Managed Subcutaneous Basal Bolus Insulin Therapy in the Hospital Setting. AB - BACKGROUND: American Diabetes Association (ADA) guidelines recommend a basal bolus correction insulin regimen as the preferred method of treatment for non critically ill hospitalized patients. However, achieving ADA glucose targets safely, without hypoglycemia, is challenging. In this study we evaluated the safety and efficacy of basal bolus subcutaneous (SubQ) insulin therapy managed by providers compared to a nurse-directed Electronic Glycemic Management System (eGMS). METHOD: This retrospective crossover study evaluated 993 non-ICU patients treated with subcutaneous basal bolus insulin therapy managed by a provider compared to an eGMS. Analysis compared therapy outcomes before Glucommander (BGM), during Glucommander (DGM), and after Glucommander (AGM) for all patients. The blood glucose (BG) target was set at 140-180 mg/dL for all groups. The safety of each was evaluated by the following: (1) BG averages, (2) hypoglycemic events <40 and <70 mg/dL, and (3) percentage of BG in target. RESULT: Percentage of BG in target was BGM 47%, DGM 62%, and AGM 36%. Patients' BGM BG average was 195 mg/dL, DGM BG average was 169 mg/dL, and AGM BG average was 174 mg/dL. Percentage of hypoglycemic events <70 mg/dL was 2.6% BGM, 1.9% DGM, and 2.8% AGM treatment. CONCLUSION: Patients using eGMS in the DGM group achieved improved glycemic control with lower incidence of hypoglycemia (<40 mg/dL and <70 mg/dl) compared to both BGM and AGM management with standard treatment. These results suggest that an eGMS can safely maintain glucose control with less hypoglycemia than basal bolus treatment managed by a provider. PMID- 27555603 TI - Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training. AB - Background: Exercise promotes repair processes in the mouse brain and improves cognition in both mice and humans. It is not known whether these benefits translate to human brain injury, particularly the significant injury observed in children treated for brain tumors. Methods: We conducted a clinical trial with crossover of exercise training versus no training in a restricted sample of children treated with radiation for brain tumors. The primary outcome was change in brain structure using MRI measures of white matter (ie, fractional anisotropy [FA]) and hippocampal volume [mm3]). The secondary outcome was change in reaction time (RT)/accuracy across tests of attention, processing speed, and short-term memory. Linear mixed modeling was used to test the effects of time, training, training setting, and carryover. Results: Twenty-eight participants completed training in either a group (n=16) or a combined group/home (n=12) setting. Training resulted in increased white matter FA (Delta=0.05, P<.001). A carryover effect was observed for participants ~12 weeks after training (Delta=0.05, P<.001). Training effects were observed for hippocampal volume (Delta=130.98mm3; P=.001) and mean RT (Delta=-457.04ms, P=0.36) but only in the group setting. Related carryover effects for hippocampal volume (Delta=222.81mm3, P=.001), and RT (Delta=-814.90ms, P=.005) were also observed. Decreased RT was predicted by increased FA (R=-0.62, P=.01). There were no changes in accuracy. Conclusions: Exercise training is an effective means for promoting white matter and hippocampal recovery and improving reaction time in children treated with cranial radiation for brain tumors. PMID- 27555604 TI - Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. AB - Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty-seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute-Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay for mucositis development and progression in silymarin group. Prophylactic administration of conventional form of silymarin tablets could significantly reduce the severity of radiotherapy induced mucositis and delay its occurrence in patients with head and neck cancer. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27555606 TI - Coronary thrombosis in diabetes: Are we doing enough? PMID- 27555605 TI - Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. AB - BACKGROUND: Tazemetostat (EPZ-6438) is a selective inhibitor of the histone methyltransferase EZH2 and currently in clinical development for non-Hodgkin lymphoma and genetically defined tumors. PROCEDURES: Tazemetostat was tested against the Pediatric Preclinical Testing Program (PPTP) solid tumor xenografts using a dose of 400 mg/kg administered twice daily by oral gavage for 28 days. H3K27me3:H3 ratios were determined in control and treated tumors. RESULTS: Tazemetostat induced significant differences in event-free survival (EFS) distribution compared with control in nine of 30 (30%) of the xenografts studied. Significant differences in EFS distribution were observed in five of seven (71%) rhabdoid tumor xenograft lines compared with four of 23 (17%) nonrhabdoid xenograft lines (chi-square [chi2 ] test P = 0.006). Tazemetostat induced tumor growth inhibition meeting criteria for intermediate and high EFS treated-to control (T/C) activity in two of 25 (8%) and one of 25 (4%) xenografts, respectively. Intermediate and high activity for the EFS T/C metric was observed exclusively among rhabdoid tumor xenografts (three of five rhabdoid tumor vs 0 of 22 nonrhabdoid tumors (chi2 test P < 0.001). One rhabdoid tumor xenograft (G401) showed stable disease. For one rhabdoid tumor (G401), delayed tumor regression to tazemetostat was noted following 1 week of tumor growth. Tazemetostat induced significant reduction of H3K27me3 levels in the majority of tumors compared with controls. CONCLUSIONS: Tazemetostat demonstrated significant antitumor activity in rhabdoid tumor models but showed no consistent activity against any other histology. Tazemetostat reduced H3K27me3 levels irrespective of tumor response. Further preclinical testing to evaluate tazemetostat in combination with other anticancer agents is warranted. PMID- 27555607 TI - 'The Rule of Six 2s': teaching learners simple strategies for structuring an outpatient adult primary care follow-up visit in the 21st century. PMID- 27555608 TI - Association between blood lead levels and blood pressures in a non-smoking healthy Korean population. AB - OBJECTIVE: The Korea National Health and Nutrition Examination Survey (KNHANES) has been performed every 3 years in Korea to help prevent cardiovascular mortality in the general population. Previous studies showed an association between blood lead levels and cardiovascular mortality. In order to assess the relationship between blood lead concentration and blood pressure in the healthy general population, we investigated whether blood lead levels were related to blood pressure in a non-smoking healthy population without any known medical diseases in the 2013 KNHANES. METHODS: 896 (mean age 40.55+/-13.83 years; body mass index 23.06+/-3.33 kg/m2) subjects who had no known diseases were included among 8018 subjects. Exclusion criteria were: hypertension, diabetes, hyperlipidaemia, cerebrovascular events, renal insufficiency, liver cirrhosis, thyroid dysfunction, any cardiovascular or renal disease, and any malignancy. Blood pressures were measured three times by sphygmomanometers, 5 min apart. Blood pressures were then expressed as the average between the second and third values. Height, weight, waist circumferences and blood pressure, as well as total cholesterol, high density lipoprotein cholesterol, triglycerides, low density lipoprotein cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), white blood cell count and blood lead levels were measured. In addition, dietary components were analysed by 24 hour recall. RESULTS: The association between log blood lead levels and systolic/diastolic pressure was stronger after it was controlled for age, sex, education, body mass index (BMI), waist circumference and fasting plasma glucose (FPG) (p=0.048, 0.002). Furthermore, the association between log blood lead levels and systolic pressure (p=0.048) and diastolic pressure (p=0.002) was more evident when controlled for age, sex, education, BMI, waist circumference, FPG, AST and ALT. CONCLUSIONS: Blood lead levels are significant determinants of systolic and diastolic blood pressure in a healthy Korean population, irrespective of sociodemographic factors and metabolic derangements. PMID- 27555609 TI - Highly Efficient Water Oxidation Photoanode Made of Surface Modified LaTiO2 N Particles. AB - An improved variation of highly active/durable O2 -evolving LaTiO2 N powder-based photoelectrode has been fabricated by pre-cleaning the powder with mild polysulfonic acid and by homogeneous deposition of CoOx co-catalyst aided by microwave annealing. The treatment in aqueous solution of poly(4-styrene sulfonic acid) results in removal of surface LaTiO2 N layers, forming fine pores in the crystallites. The CoOx co-catalyst by microwave deposition in Co(NH3 )6 Cl3 /ethylene glycol homogeneously covers the particle surface. The LaTiO2 N powder is fabricated into particle-transferred electrodes on Ti thin film supported on solid substrate. The modified LaTiO2 N grains on the electrode serve as a highly active O2 -evolving photoanode achieving 8.9 mA cm-2 of the photocurrent density at 1.23 V versus reversible hydrogen electrode (RHE) in 0.1 m NaOH (pH 13) under solar-simulator irradiation Airmass 1.5 Global (AM 1.5G). The activity has been much improved, compared with conventional LaTiO2 N treated in mineral acid or with CoOx deposited by impregnation. The new electrode also exhibits better durability in fixed-potential chronoamperometric tests under AM 1.5G irradiation. PMID- 27555610 TI - Plasma metabolic profile delineates roles for neurodegeneration, pro-inflammatory damage and mitochondrial dysfunction in the FMR1 premutation. AB - Carriers of premutation CGG expansions in the fragile X mental retardation 1 (FMR1) gene are at higher risk of developing a late-onset neurodegenerative disorder named Fragile X-associated tremor ataxia syndrome (FXTAS). Given that mitochondrial dysfunction has been identified in fibroblasts, PBMC and brain samples from carriers as well as in animal models of the premutation and that mitochondria are at the center of intermediary metabolism, the aim of the present study was to provide a complete view of the metabolic pattern by uncovering plasma metabolic perturbations in premutation carriers. To this end, metabolic profiles were evaluated in plasma from 23 premutation individuals and 16 age- and sex-matched controls. Among the affected pathways, mitochondrial dysfunction was associated with a Warburg-like shift with increases in lactate levels and altered Krebs' intermediates, neurotransmitters, markers of neurodegeneration and increases in oxidative stress-mediated damage to biomolecules. The number of CGG repeats correlated with a subset of plasma metabolites, which are implicated not only in mitochondrial disorders but also in other neurological diseases, such as Parkinson's, Alzheimer's and Huntington's diseases. For the first time, the identified pathways shed light on disease mechanisms contributing to morbidity of the premutation, with the potential of assessing metabolites in longitudinal studies as indicators of morbidity or disease progression, especially at the early preclinical stages. PMID- 27555611 TI - Decoding common and divergent cellular functions of the domains of forkhead transcription factors Fkh1 and Fkh2. AB - Forkhead transcription factors play a key role in embryonic patterning during development. In Saccharomyces cerevisiae, two forkhead transcription factors, Fkh1 and Fkh2, regulate the transcription of CLB2 cluster genes important for mitosis. Fkh1 reduces, whereas Fkh2 elevates, the transcription of CLB2 cluster genes. However, the mechanism for this observation remains unclear. Fkh1 and Fkh2 each contain a forkhead domain (DNA-binding domain, DBD) and a forkhead associated domain (FHAD), whereas Fkh2 possesses an extra C' domain containing six consensus cyclin-dependent kinase phosphorylation sites. In the present study, roles of these domains in protein complexes, the regulation of cell growth and CLB2 cluster genes and protein interactions were investigated using various domain mutants. The result showed that the DBD was vital for ternary complex formation with Mcm1, whereas the FHAD was central for the regulation of cell growth and CLB2 cluster transcription and for interactions with Ndd1 and Clb2. However, the Fkh2 C' domain was dispensable for the above functions. Both DBDs and FHADs had functional divergences in the cell, and Ndd1 functioned via its phosphorylated form. These data provide important insights into the functional mechanism of Fkh1 and Fkh2 in cell cycle control. PMID- 27555612 TI - Methylglyoxal-induced dicarbonyl stress in aging and disease: first steps towards glyoxalase 1-based treatments. AB - Dicarbonyl stress is the abnormal accumulation of dicarbonyl metabolites leading to increased protein and DNA modification contributing to cell and tissue dysfunction in aging and disease. It is produced by increased formation and/or decreased metabolism of dicarbonyl metabolites. MG (methylglyoxal) is a dicarbonyl metabolite of relatively high flux of formation and precursor of the most quantitatively and functionally important spontaneous modifications of protein and DNA clinically. Major MG-derived adducts are arginine-derived hydroimidazolones of protein and deoxyguanosine-derived imidazopurinones of DNA. These are formed non-oxidatively. The glyoxalase system provides an efficient and essential basal and stress-response-inducible enzymatic defence against dicarbonyl stress by the reduced glutathione-dependent metabolism of methylglyoxal by glyoxalase 1. The GLO1 gene encoding glyoxalase 1 has low prevalence duplication and high prevalence amplification in some tumours. Dicarbonyl stress contributes to aging, disease and activity of cytotoxic chemotherapeutic agents. It is found at a low, moderate and severe level in obesity, diabetes and renal failure respectively, where it contributes to the development of metabolic and vascular complications. Increased glyoxalase 1 expression confers multidrug resistance to cancer chemotherapy and has relatively high prevalence in liver, lung and breast cancers. Studies of dicarbonyl stress are providing improved understanding of aging and disease and the basis for rational design of novel pharmaceuticals: glyoxalase 1 inducers for obesity, diabetes and cardiovascular disease and glyoxalase 1 inhibitors for multidrug resistant tumours. The first clinical trial of a glyoxalase 1 inducer in overweight and obese subjects showed improved glycaemic control, insulin resistance and vascular function. PMID- 27555613 TI - Molecular mechanisms of appetite and obesity: a role for brain AMPK. AB - Feeding behaviour and energy storage are both crucial aspects of survival. Thus, it is of fundamental importance to understand the molecular mechanisms regulating these basic processes. The AMP-activated protein kinase (AMPK) has been revealed as one of the key molecules modulating energy homoeostasis. Indeed, AMPK appears to be essential for translating nutritional and energy requirements into generation of an adequate neuronal response, particularly in two areas of the brain, the hypothalamus and the hindbrain. Failure of this physiological response can lead to energy imbalance, ultimately with extreme consequences, such as leanness or obesity. Here, we will review the data that put brain AMPK in the spotlight as a regulator of appetite. PMID- 27555615 TI - Responding to the challenge of look-alike, sound-alike drug names. PMID- 27555614 TI - Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine. AB - Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene-environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases. PMID- 27555616 TI - Role of microglia in embryonic neurogenesis. AB - Microglia begin colonizing the developing brain as early as embryonic day 9, prior to the emergence of neurons and other glia. Their ontogeny is also distinct from other central nervous system cells, as they derive from yolk sac hematopoietic progenitors and not neural progenitors. In this review, we feature these unique characteristics of microglia and assess the spatiotemporal similarities between microglia colonization of the central nervous system and embryonic neurogenesis. We also infer to existing evidence for microglia function from embryonic through to postnatal neurodevelopment to postulate roles for microglia in neurogenesis. PMID- 27555617 TI - Residual Volume and Total Lung Capacity to Assess Reversibility in Obstructive Lung Disease. AB - BACKGROUND: Reversibility of obstructive lung disease is traditionally defined by changes in FEV1 or FVC in response to bronchodilators. These may not fully reflect changes due to a reduction in hyperinflation or air-trapping, which have important clinical implications. To date, only a handful of studies have examined bronchodilators' effect on lung volumes. The authors sought to better characterize the response of residual volume and total lung capacity to bronchodilators. METHODS: Responsiveness of residual volume and total lung capacity to bronchodilators was assessed with a retrospective analysis of pulmonary function tests of 965 subjects with obstructive lung disease as defined by the lower limit of normal based on National Health and Nutritional Examination Survey III prediction equations. RESULTS: A statistically significant number of subjects demonstrated response to bronchodilators in their residual volume independent of response defined by FEV1 or FVC, the American Thoracic Society and European Respiratory Society criteria. Reduced residual volume weakly correlated with response to FEV1 and to FVC. No statistically significant correlation was found between total lung capacity and either FEV1 or FVC. CONCLUSIONS: A significant number of subjects classified as being nonresponsive based on spirometry have reversible residual volumes. Subjects whose residual volumes improve in response to bronchodilators represent an important subgroup of those with obstructive lung disease. The identification of this subgroup better characterizes the heterogeneity of obstructive lung disease. The clinical importance of these findings is unclear but warrants further study. PMID- 27555618 TI - Rhinopharyngeal Retrograde Clearance Induces Less Respiratory Effort and Fewer Adverse Effects in Comparison With Nasopharyngeal Aspiration in Infants With Acute Viral Bronchiolitis. AB - BACKGROUND: Acute viral bronchiolitis is an inflammatory disease of the lower respiratory tract. This study aimed to compare the immediate effects of retrograde rhinopharyngeal clearance with nasopharyngeal aspiration in children admitted with acute viral bronchiolitis. METHODS: This was a randomized controlled clinical trial with children admitted for acute viral bronchiolitis up to 12 months old. Subjects were divided into a nasopharyngeal aspiration group and a clearance group, submitted to retrograde rhinopharyngeal clearance with physiological solution (0.9%) instillation. In both groups, there were 3 evaluations on the same day (data collections 1, 2, and 3), including cardiorespiratory parameters, clinical score of respiratory dysfunction, and adverse effects. RESULTS: One hundred children were included, with no statistical differences between groups regarding the characteristics of the sample. There was a significant reduction (P < .05) in heart rate in data collections 1 and 2 after 10 and 30 min. The number of episodes of nasal bleeding (28 vs 1) and vomiting (11 vs 7) was higher in the aspiration group compared with the clearance group. Children classified as moderate showed a significant reduction of retractions (100% vs 84.6%) and nasal bleeding (44.8% vs 0%). An increase of 6.7 and 19.5% in wheezing and retractions, respectively, was shown for the aspiration group, whereas the clearance group showed only 4.6% for both parameters. CONCLUSIONS: The use of retrograde rhinopharyngeal clearance in the management of infants with acute viral bronchiolitis can be an alternative for the clearance of the upper airways, since it showed immediate positive effects on the occurrence of complications and signs of respiratory effort compared with nasopharyngeal aspiration. Children classified with a moderate clinical score appear to benefit the most. (ClinicalTrials.gov registration NCT02460614.). PMID- 27555619 TI - Compensating Artificial Airway Resistance via Active Expiration Assistance. AB - BACKGROUND: Artificial airway resistance as provided by small-lumen tracheal tubes or catheters increases the risk of intrinsic PEEP (PEEPi). We hypothesized that by active expiration assistance, larger minute volumes could be generated without causing PEEPi compared with conventional mechanical ventilation when using small-lumen tracheal tubes or a cricothyrotomy catheter. METHODS: We investigated the active expiration assistance in a physical model of the respiratory system and estimated its hypothetical performance in terms of maximal flow generated with endotracheal tubes ranging from 3.0 to 8.0 mm inner diameter (ID); with microlaryngeal tubes of 4.0, 5.0, and 6.0 mm ID; and with a cricothyrotomy catheter. Furthermore, we determined the minute volumes that could be achieved without generating PEEPi by ventilating a physical lung model using conventional mechanical ventilation or using active expiration assistance. RESULTS: The inspiratory and expiratory flow during active expiration assistance increased with increasing supply flow and decreased with decreasing ID of the connected endotracheal tubes (both P < .001). With small-lumen tracheal tubes, the active expiration assistance generated similar or higher minute volumes than conventional ventilation. Conventional mechanical ventilation with PEEPi <1 cm H2O was not achievable via a microlaryngeal tube of 4.0 mm ID and smaller lumen tubes. CONCLUSIONS: For mechanical ventilation via small-lumen tubes or thin catheters, active compensation of airway resistance might be a necessary means to generate adequate minute ventilation without causing PEEPi. Active expiration assistance can generate reasonable respiratory minute volumes via small-lumen tubes or thin catheters. PMID- 27555621 TI - George A. Bray, MD: Progress in Obesity-Multidisciplinary Research, Multidimensional Man. PMID- 27555622 TI - Diagnosed and Undiagnosed Diabetes Prevalence by County in the U.S., 1999-2012. AB - OBJECTIVE: Previous analyses of diabetes prevalence in the U.S. have considered either only large geographic regions or only individuals in whom diabetes had been diagnosed. We estimated county-level trends in the prevalence of diagnosed, undiagnosed, and total diabetes as well as rates of diagnosis and effective treatment from 1999 to 2012. RESEARCH DESIGN AND METHODS: We used a two-stage modeling procedure. In the first stage, self-reported and biomarker data from the National Health and Nutrition Examination Survey (NHANES) were used to build models for predicting true diabetes status, which were applied to impute true diabetes status for respondents in the Behavioral Risk Factor Surveillance System (BRFSS). In the second stage, small area models were fit to imputed BRFSS data to derive county-level estimates of diagnosed, undiagnosed, and total diabetes prevalence, as well as rates of diabetes diagnosis and effective treatment. RESULTS: In 2012, total diabetes prevalence ranged from 8.8% to 26.4% among counties, whereas the proportion of the total number of cases that had been diagnosed ranged from 59.1% to 79.8%, and the proportion of successfully treated individuals ranged from 19.4% to 31.0%. Total diabetes prevalence increased in all counties between 1999 and 2012; however, the rate of increase varied widely. Over the same period, rates of diagnosis increased in all counties, while rates of effective treatment stagnated. CONCLUSIONS: Our findings demonstrate substantial disparities in diabetes prevalence, rates of diagnosis, and rates of effective treatment within the U.S. These findings should be used to target high burden areas and select the right mix of public health strategies. PMID- 27555623 TI - Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990 to 2010. AB - OBJECTIVE: To estimate global and regional trends from 1990 to 2010 of the prevalence and number of persons visually impaired specifically by diabetic retinopathy (DR), as a complication of the precipitous trends in global diabetes, is fundamental for health planning purposes. RESEARCH DESIGN AND METHODS: The meta-analysis of published population studies from 1990 to 2012 for the Global Burden of Disease Study 2010 (GBD) yielded estimated global regional trends in DR among other causes of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18, >=3/60) and blindness (presenting visual acuity <3/60). RESULTS: Globally in 2010, out of overall 32.4 million blind and 191 million visually impaired people, 0.8 million were blind and 3.7 million were visually impaired because of DR, with an alarming increase of 27% and 64%, respectively, spanning the two decades from 1990 to 2010. DR accounted for 2.6% of all blindness in 2010 and 1.9% of all MSVI worldwide, increasing from 2.1% and 1.3%, respectively, in 1990. These figures were lower in regions with younger populations (<2% in East and Southeast Asia and Oceania) than in high-income regions (North America, Western Europe, and Australasia) with relatively aging populations (>4%). CONCLUSIONS: The number of persons with visual impairment due to DR worldwide is rising and represents an increasing proportion of all blindness/MSVI causes. Age-standardized prevalence of DR-related blindness/MSVI was higher in sub-Saharan Africa and South Asia. One out of 39 blind people had blindness due to DR, and 1 out of 52 visually impaired people had visual impairment due to DR. PMID- 27555624 TI - Diagnostic Dilemma: Clinical and Histological Abnormalities in a Hispanic Patient With Diabetes. PMID- 27555625 TI - Erratum. Classification and diagnosis of diabetes. Sec. 2. In Standards of Medical Care in Diabetes-2016. Diabetes Care 2016;39(Suppl. 1):S13-S22. PMID- 27555627 TI - Comment on Podmore et al. Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study. Diabetes Care 2016;39:572-581. PMID- 27555628 TI - Comment on Muraki et al. Potato Consumption and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies. Diabetes Care 2016;39:376-384. PMID- 27555629 TI - Response to Comment on Muraki et al. Potato Consumption and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies. Diabetes Care 2016;39:376-384. PMID- 27555630 TI - Comment on Beltrand et al. Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations. Diabetes Care 2015;38:2033-2041. PMID- 27555631 TI - Response to Comment on Beltrand et al. Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations. Diabetes Care 2015;38:2033-2041. PMID- 27555632 TI - Comment on Kovatchev and Cobelli. Glucose Variability: Timing, Risk Analysis, and Relationship to Hypoglycemia in Diabetes. Diabetes Care 2016;39:502-510. PMID- 27555633 TI - Response to Comment on Kovatchev and Cobelli. Glucose Variability: Timing, Risk Analysis, and Relationship to Hypoglycemia in Diabetes. Diabetes Care 2016;39:502 510. PMID- 27555634 TI - Comment on Yang et al. Association of Statin Use and Reduced Risk of Lower Extremity Amputation Among Patients With Diabetes: A Nationwide Population-Based Cohort Observation. Diabetes Care 2016;39:e54-e55. PMID- 27555635 TI - Response to Comment on Yang et al. Association of Statin Use and Reduced Risk of Lower-Extremity Amputation Among Patients With Diabetes: A Nationwide Population Based Cohort Observation. Diabetes Care 2016;39:e54-e55. PMID- 27555636 TI - Moderate drinkers may not have reduced risk of all-cause mortality: a lifecourse perspective. PMID- 27555637 TI - Colorectal cancer screening is cost-effective in the elderly who have had less intense prior screening, high baseline risk of colorectal cancer and less comorbidities. PMID- 27555638 TI - Late-life increases in alcohol consumption among postmenopausal women appear associated with greater breast cancer risk and less coronary heart disease risk. PMID- 27555639 TI - Smokers with respiratory symptoms but no airflow limitation, often have activity limitation, exacerbations and evidence of airway disease. PMID- 27555640 TI - Metformin reduces weight gain in overweight/obese adolescents with type 1 diabetes. PMID- 27555641 TI - Reduction in general intelligence and executive function persists into adulthood among very preterm or very low birthweight children. PMID- 27555643 TI - Environmental Heterogeneity in Parasitoid-Host Interaction for Mutillidae (Hymenoptera: Apocrita). AB - Environmental heterogeneity is a major factor influencing the spatial distribution of organisms. Due to intimate relationships with their hosts, parasitic insects are inclined to be even more sensitive to variations. This study aimed to verify the relationship between spatial distribution of Mutillidae, potential hosts, and the effect of heterogeneity in the distribution of both, testing the hypotheses: i) the spatial distribution of mutillids depends on the distribution of hosts and ii) variation in environmental heterogeneity affects the distribution of both. Sampling was conducted in four fragments of the Cerrado. We collected Hymenopteran specimens from 25 plots of one hectare using 18 Malaise traps throughout one year, totalizing 32,400 trap-hours. Female Mutillidae were hand collected at all sampling points, for a total of 450 man hours. At each hectare plot, we obtained the environmental variables from nine plots of 25 m2 A total of 1,089 individuals were collected (Apidae: 311; Crabronidae: 165; Shpecidae: 84; Vespidae: 229) belonging to 127 species of potential hosts (bees and wasps) and 300 individuals (42 species) of Mutillidae. Leaf-litter depths showed significant relation in host-parasitoid distribution. The spatiotemporal distribution followed the predator-prey model for Mutillidae, and environmental heterogeneity was a factor that determined the structure of the host-parasitoid community. The results suggest an intense relationship between the Mutillidae and Crabronidae, as well as Sphecidae and two Apidae subfamilies (Halictinae and Colletinae). These families and subfamilies present behavior in which they build nests in aggregations even each female being solitary. Crabronidae is considered the best potential host for Mutillidae. PMID- 27555642 TI - Inflammatory Bowel Disease Incidence is on the Continuous Rise Among All Paediatric Patients Except for the Very Young: A Nationwide Registry-based Study on 28-Year Follow-up. AB - BACKGROUND AND AIMS: The burden of inflammatory bowel disease [IBD] in health care is high. We conducted research on the temporal changes in the incidence of paediatric IBD [PIBD] using nationwide registry-based data in Finland. METHODS: All PIBD cases diagnosed at less than 20 years of age during 1987-2014 [in total, 5415 patients] were retrieved from a database documenting reimbursements for drug costs. Incidence rates were calculated by dividing the number of annual new PIBD cases by the size of the paediatric population at risk during each calendar year. Temporal trends in the incidences of PIBD and its subtypes, ulcerative colitis [UC] and Crohn's disease [CD], were estimated using Poisson regression analyses. RESULTS: The mean annual incidence of PIBD increased from 7/100000 for the years 1987-1990 to 23/100000 for the years 2011-2014. The average rate of increase was 4.1% (95% confidence interval [CI]: 3.6-4.5) per annum. In the period 2000-2014, the increase rate in the annual incidence of UC [3.8%; 95% CI: 2.7-5.0], was steeper than for CD [2.5%; 95% CI: 1.0-3.8]. The most pronounced increase occurred in UC among adolescents aged 16-19 years [4.8%; 95% CI: 2.9-6.7]. For children less than 10 years of age, the rate of change remained low. Approximately 0.17% of the birth cohort for the years 1999-2000 was diagnosed with PIBD by the age of 14 years. CONCLUSION: The incidence of PIBD is primarily increasing among adolescents, challenging the identification of the possible environmental triggers for the disease. PMID- 27555644 TI - Effects of changing sea ice on marine mammals and subsistence hunters in northern Alaska from traditional knowledge interviews. AB - Marine mammals are important sources of food for indigenous residents of northern Alaska. Changing sea ice patterns affect the animals themselves as well as access to them by hunters. Documenting the traditional knowledge of Inupiaq and Yupik hunters concerning marine mammals and sea ice makes accessible a wide range of information relevant to understanding the ecosystem to which humans belong. We interviewed hunters in 11 coastal villages from the northern Bering Sea to the Beaufort Sea. Hunters reported extensive changes in sea ice and weather that have affected the timing of marine mammal migrations, their distribution and behaviour and the efficacy of certain hunting methods. Amidst these changes, however, hunters cited offsetting technological benefits, such as more powerful and fuel efficient outboard engines. Other concerns included potential impacts to subsistence hunting from industrial activity such as shipping and oil and gas development. While hunters have been able to adjust to some changes, continued environmental changes and increased disturbance from human activity may further challenge their ability to acquire food in the future. There are indications, however, that innovation and flexibility provide sources of resilience. PMID- 27555645 TI - Selective disappearance of individuals with high levels of glycated haemoglobin in a free-living bird. AB - Although disruption of glucose homeostasis is a hallmark of ageing in humans and laboratory model organisms, we have little information on the importance of this process in free-living animals. Poor control of blood glucose levels leads to irreversible protein glycation. Hence, levels of protein glycation are hypothesized to increase with age and to be associated with a decline in survival. We tested these predictions by measuring blood glycated haemoglobin in 274 adult collared flycatchers of known age and estimating individual probability of recapture in the following 2 years. Results show a strong decrease in glycated haemoglobin from age 1 to 5 years and an increase thereafter. Individuals with high levels of glycated haemoglobin had a lower probability of recapture, even after controlling for effects of age and dispersal. Altogether, our findings suggest that poor control of glucose homoeostasis is associated with lower survival in this free-living bird population, and that the selective disappearance of individuals with the highest glycation levels could account for the counterintuitive age-related decline in glycated haemoglobin in the early age categories. PMID- 27555646 TI - Whither life? Conjectures on the future evolution of biochemistry. AB - Life has existed on the Earth for approximately four billion years. The sheer depth of evolutionary time, and the diversity of extant species, makes it tempting to assume that all the key biochemical innovations underpinning life have already happened. But we are only a little over halfway through the trajectory of life on our planet. In this Opinion piece, we argue: (i) that sufficient time remains for the evolution of new processes at the heart of metabolic biochemistry and (ii) that synthetic biology is providing predictive insights into the nature of these innovations. By way of example, we focus on engineered solutions to existing inefficiencies in energy generation, and on the complex, synthetic regulatory circuits that are currently being implemented. PMID- 27555647 TI - Nepotism and subordinate tenure in a cooperative breeder. AB - In many cooperatively breeding societies, subordinate individuals delay dispersal and independent breeding. The length of time that subordinates delay dispersal (subordinate tenure) is likely to have important implications for both subordinate and dominant fitness. However, quantitative comparisons of the subordinate tenure of males and females are rare, especially with respect to the presence of same- versus opposite-sex close kin. Here, we investigate subordinate tenure and how it is affected by the genetic relationship between subordinates and dominants in the cooperatively breeding southern pied babbler (Turdoides bicolor). We find that for males, longer subordinate tenures result in increased likelihood of attaining dominance. In the presence of an unrelated dominant male, tenure of subordinate males is significantly shorter, indicating nepotism among males. Female tenures are unaffected by the genetic relationship to either the dominant male or female. These results are some of the first to demonstrate that the sex of both the dominants and subordinates, and the genetic relationship between them, can have significant impacts on subordinate tenure and dispersal delays. Nepotism has likely played a vital role in the evolution of cooperative breeding in this species. PMID- 27555648 TI - Taxonomic distribution of cryptic diversity among metazoans: not so homogeneous after all. AB - Cryptic diversity plagues estimates of biodiversity, conservation efforts and attempts to control diseases and invasive species. Here, we re-visit a decade-old assessment of whether or not cryptic species are homogeneously reported among higher metazoan taxa. We compiled information from an extensive survey of the literature to recover all reports of cryptic species among metazoans. After correcting for currently known species richness and research effort per taxon, we find that cryptic species are over-reported in some taxa and under-reported in others. Although several taxa showing either a lack or an excess of reported cryptic species were poorly studied invertebrate groups, we found that cryptic species were over-reported in amphibians, reptiles and crustaceans, all relatively well-studied groups. The observed heterogeneity in the distribution of reported cryptic species may reflect taxon-specific properties affecting either the propensity for cryptic species to be formed or their likelihood of being detected by conventional taxonomy. Either way, the implications of cryptic diversity may not apply equally across all taxonomic groups. PMID- 27555649 TI - Cross-modal individual recognition in wild African lions. AB - Individual recognition is considered to have been fundamental in the evolution of complex social systems and is thought to be a widespread ability throughout the animal kingdom. Although robust evidence for individual recognition remains limited, recent experimental paradigms that examine cross-modal processing have demonstrated individual recognition in a range of captive non-human animals. It is now highly relevant to test whether cross-modal individual recognition exists within wild populations and thus examine how it is employed during natural social interactions. We address this question by testing audio-visual cross-modal individual recognition in wild African lions (Panthera leo) using an expectancy violation paradigm. When presented with a scenario where the playback of a loud call (roaring) broadcast from behind a visual block is incongruent with the conspecific previously seen there, subjects responded more strongly than during the congruent scenario where the call and individual matched. These findings suggest that lions are capable of audio-visual cross-modal individual recognition and provide a useful method for studying this ability in wild populations. PMID- 27555650 TI - A single origin of extreme matrotrophy in African mabuyine skinks. AB - Most mammals and approximately 20% of squamates (lizards and snakes) are viviparous, whereas all crocodilians, birds and turtles are oviparous. Viviparity evolved greater than 100 times in squamates, including multiple times in Mabuyinae (Reptilia: Scincidae), making this group ideal for studying the evolution of nutritional patterns associated with viviparity. Previous studies suggest that extreme matrotrophy, the support of virtually all of embryonic development by maternal nutrients, evolved as many as three times in Mabuyinae: in Neotropical Mabuyinae (63 species), Eumecia (2 species; Africa) and Trachylepis ivensii (Africa). However, no explicit phylogenetic hypotheses exist for understanding the evolution of extreme matrotrophy. Using multilocus DNA data, we inferred a species tree for Mabuyinae that implies that T. ivensii (here assigned to the resurrected genus Lubuya) is sister to Eumecia, suggesting that extreme matrotrophy evolved only once in African mabuyine skinks. PMID- 27555651 TI - Oceanic circulation models help to predict global biogeography of pelagic yellow bellied sea snake. AB - It is well recognized that most marine vertebrates, and especially tetrapods, precisely orient and actively move in apparently homogeneous oceanic environments. Here, we investigate the presumptive role of oceanic currents in biogeographic patterns observed in a secondarily marine tetrapod, the yellow bellied sea snake (Hydrophis [Pelamis] platurus). State-of-the-art world ocean circulation models show how H. platurus, the only pelagic species of sea snake, can potentially exploit oceanic currents to disperse and maintain population mixing between localities that spread over two-thirds of the Earth's circumference. The very close association of these snakes with surface currents seems to provide a highly efficient dispersal mechanism that allowed this species to range extensively and relatively quickly well beyond the central Indo-Pacific area, the centre of origin, abundance and diversity of sea snakes. Our results further suggest that the pan-oceanic population of this species must be extraordinarily large. PMID- 27555652 TI - Behavioural phenotypes predict disease susceptibility and infectiousness. AB - Behavioural phenotypes may provide a means for identifying individuals that disproportionally contribute to disease spread and epizootic outbreaks. For example, bolder phenotypes may experience greater exposure and susceptibility to pathogenic infection because of distinct interactions with conspecifics and their environment. We tested the value of behavioural phenotypes in larval amphibians for predicting ranavirus transmission in experimental trials. We found that behavioural phenotypes characterized by latency-to-food and swimming profiles were predictive of disease susceptibility and infectiousness defined as the capacity of an infected host to transmit an infection by contacts. While viral shedding rates were positively associated with transmission, we also found an inverse relationship between contacts and infections. Together these results suggest intrinsic traits that influence behaviour and the quantity of pathogens shed during conspecific interactions may be an important contributor to ranavirus transmission. These results suggest that behavioural phenotypes provide a means to identify individuals more likely to spread disease and thus give insights into disease outbreaks that threaten wildlife and humans. PMID- 27555653 TI - The reef-building coral Acropora conditionally hybridize under sperm limitation. AB - Multi-specific synchronous spawning risks both sperm limitation, which reduces fertilization success, and hybridization with other species. If available sperm of conspecifics are limited, hybridization with heterospecific sperm could be an alternative. Some species of the reef-building coral Acropora produce hybrid offspring in vitro, and therefore hybridization between such species does sometimes occur in nature. Here, we report that the interbreeding species Acropora florida and A. intermedia preferentially bred with conspecifics at optimal gamete concentrations (10(6) cells ml(-1)), but when sperm concentration was low (10(4) cells ml(-1)), A florida eggs displayed an increased incidence of fertilization by sperm of A intermedia However, A intermedia eggs never crossed with heterospecific sperm, regardless of gamete concentrations. It appears that A florida eggs conditionally hybridize with heterospecific sperm; in nature, this would allow A florida to cross with later-spawning species such as A intermedia These results indicate that hybridization between some Acropora species could occur in nature according to the number of available sperm, and the choice of heterospecific sperm for fertilization could be one of the fertilization strategies in the sperm-limited condition. PMID- 27555654 TI - The Latin American Biological Dosimetry Network (LBDNet). AB - Biological Dosimetry is a necessary support for national radiation protection programmes and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American Region. Here are presented the main topics considered in the foundational document of the network, which comprise: mission, partners, concept of operation, including the mechanism to request support for biological dosimetry assistance in the region, and the network capabilities. The process for network activation and the role of the coordinating laboratory during biological dosimetry emergency response is also presented. This information is preceded by historical remarks on biological dosimetry cooperation in Latin America. A summary of the main experimental and practical results already obtained by the LBDNet is also included. PMID- 27555656 TI - The Mayak Worker Dosimetry System (MWDS-2013): A Bayesian Analysis to Quantify Pulmonary Binding of Plutonium in Lungs Using Historic Beagle Dog Data. AB - The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protection's (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, fb, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, sb The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (239Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data. PMID- 27555655 TI - Measurement of the Dose to the Family Members Taking Care of Thyroid Cancer Patients Undergoing I-131 Therapy in Nuclear Medicine Using TLD-100. AB - The family members or friends of the patients undergoing treatment using radioiodine in nuclear medicine are inevitably exposed to ionization radiation. The purpose of this study is measurement of the dose received by the people taking care of the thyroid cancer patients treated by 131I. For this purpose, the dose amounts received by 29 people accompanying patients were measured using thermoluminescence dosimeters. A badge containing three TLD-100 chips was given to each caregiver. The people were asked to wear the badges for 24 days, when they are taking care of the patients. Finally the dose to each person was estimated by averaging the readings of the three TLDs. The measured dose amounts to the people were compared with the recommendations of international commitions. According to the results obtained in this study, the amounts of dose received by the caregivers were between 0.03 and 0.38 mSv, with the average of 0.12 mSv. By comparison of the results of this study with the recommendations of International Commission on Radiological Protection (ICRP), it can be observed that the dose to family members of the patients is less than the dose constraints. However, it is recommended that the caregivers be aware of the radiation protection principles in order to reduce their dose. PMID- 27555657 TI - Evolution and Optimization of Tooth Models for Testing In Vivo EPR Tooth Dosimetry. AB - Testing and verification are an integral part of any cycle to design, manufacture and improve a novel device intended for use in humans. In the case of testing Dartmouth's electron paramagnetic resonance (EPR) in vivo tooth dosimetry device, in vitro studies are needed throughout its development to test its performance, i.e. to verify its current capability for assessing dose in individuals potentially exposed to ionizing radiation. Since the EPR device uses the enamel of human teeth to assess dose, models that include human teeth have been an integral mechanism to carry out in vitro studies during development and testing its ability to meet performance standards for its ultimate intended in vivo use. As the instrument improves over time, new demands for in vitro studies change as well. This paper describes the tooth models used to perform in vitro studies and their evolution to meet the changing demands for testing in vivo EPR tooth dosimetry. PMID- 27555658 TI - Proceedings of the 14th Coordination and Planning Meeting of the WHO-REMPAN: Radiation Emergency Medical Preparedness and Assistance Network, Wuerzburg, Germany, 07-09 MAY 2014. PMID- 27555659 TI - Relationship Between Objectively Measured Sedentary Behavior and Cognitive Performance in Patients With Schizophrenia Vs Controls. AB - Objective: Sedentary behavior (SB) is associated with poor cognitive performance in the general population. Although people with schizophrenia are highly sedentary and experience marked cognitive impairments, no study has investigated the relationship between SB and cognition in people with schizophrenia. Methods: A total of 199 inpatients with schizophrenia (mean [SD] age 44.0 [9.9] years, 61.3% male, mean [SD] illness duration 23.8 [6.5]) and 60 age and sex matched controls were recruited. Sedentary behavior and physical activity (PA) were captured for 7 consecutive days with an accelerometer. Cognitive performance was assessed using the Vienna Test System, and the Grooved Pegboard Test. Multivariate regression analyses adjusting for important confounders including positive and negative symptoms, illness duration, medication, and PA were conducted. Results: The 199 patients with schizophrenia engaged in significantly more SB vs controls (581.1 (SD 127.6) vs 336.4 (SD 107.9) min per day, P < .001) and performed worse in all cognitive performance measures (all P < .001). Compared to patients with high levels of SB (n = 89), patients with lower levels of SB (n = 110) had significantly (P < .05) better motor reaction time and cognitive processing. In the fully adjusted multivariate analysis, SB was independently associated with slower motor reaction time (beta = .162, P < .05) but not other cognitive outcomes. Lower levels of PA were independently associated with worse attention and processing speed (P < .05). Conclusion: Our data suggest that higher levels of sedentary behavior and physical inactivity are independently associated with worse performance across several cognitive domains. Interventions targeting reductions in SB and increased PA should be explored. PMID- 27555661 TI - Ras and TGF-beta signaling enhance cancer progression by promoting the DeltaNp63 transcriptional program. AB - The p53 family of transcription factors includes p63, which is a master regulator of gene expression in epithelial cells. Determining whether p63 is tumor suppressive or tumorigenic is complicated by isoform-specific and cellular context-dependent protein associations, as well as antagonism from mutant p53. DeltaNp63 is an amino-terminal-truncated isoform, that is, the predominant isoform expressed in cancer cells of epithelial origin. In HaCaT keratinocytes, which have mutant p53 and DeltaNp63, we found that mutant p53 antagonized DeltaNp63 transcriptional activity but that activation of Ras or transforming growth factor-beta (TGF-beta) signaling pathways reduced the abundance of mutant p53 and strengthened target gene binding and activity of DeltaNp63. Among the products of DeltaNp63-induced genes was dual-specificity phosphatase 6 (DUSP6), which promoted the degradation of mutant p53, likely by dephosphorylating p53. Knocking down all forms of p63 or DUSP6 and DUSP7 (DUSP6/7) inhibited the basal or TGF-beta-induced or epidermal growth factor (which activates Ras)-induced migration and invasion in cultures of p53-mutant breast cancer and squamous skin cancer cells. Alternatively, overexpressing DeltaNp63 in the breast cancer cells increased their capacity to colonize various tissues upon intracardiac injection in mice, and this was inhibited by knocking down DUSP6/7 in these DeltaNp63 overexpressing cells. High abundance of DeltaNp63 in various tumors correlated with poor prognosis in patients, and this correlation was stronger in patients whose tumors also had a mutation in the gene encoding p53. Thus, oncogenic Ras and TGF-beta signaling stimulate cancer progression through activation of the DeltaNp63 transcriptional program. PMID- 27555660 TI - Dynamic DNA methylation regulates neuronal intrinsic membrane excitability. AB - Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory-related plasticity also includes alterations in intrinsic membrane excitability mediated by changes in the abundance or activity of ion channels in the plasma membrane, which sets the threshold for action potential generation. We found that prolonged inhibition of DNA methyltransferase (DNMT) activity increased intrinsic membrane excitability of cultured cortical pyramidal neurons. Knockdown of the cytosine demethylase TET1 or inhibition of RNA polymerase blocked the increased membrane excitability caused by DNMT inhibition, suggesting that this effect was mediated by subsequent cytosine demethylation and de novo transcription. Prolonged DNMT inhibition blunted the medium component of the after-hyperpolarization potential, an effect that would increase neuronal excitability, and was associated with reduced expression of the genes encoding small-conductance Ca(2+)-activated K(+) (SK) channels. Furthermore, the specific SK channel blocker apamin increased neuronal excitability but was ineffective after DNMT inhibition. Our results suggested that DNMT inhibition enables transcriptional changes that culminate in decreased expression of SK channel encoding genes and decreased activity of SK channels, thus providing a mechanism for the regulation of neuronal intrinsic membrane excitability by dynamic DNA cytosine methylation. This study has implications for human neurological and psychiatric diseases associated with dysregulated intrinsic excitability. PMID- 27555662 TI - Negative regulation of NF-kappaB p65 activity by serine 536 phosphorylation. AB - Nuclear factor kappaB (NF-kappaB) is a master regulator of inflammation and cell death. Whereas most of the activity of NF-kappaB is regulated through the inhibitor of kappaB (IkappaB) kinase (IKK)-dependent degradation of IkappaB, IKK also phosphorylates subunits of NF-kappaB. We investigated the contribution of the phosphorylation of the NF-kappaB subunit p65 at the IKK phosphorylation site serine 536 (Ser(536)) in humans, which is thought to be required for the activation and nuclear translocation of NF-kappaB. Through experiments with knock in mice (S534A mice) expressing a mutant p65 with an alanine-to-serine substitution at position 534 (the murine homolog of human Ser(536)), we observed increased expression of NF-kappaB-dependent genes after injection of mice with the inflammatory stimulus lipopolysaccharide (LPS) or exposure to gamma irradiation, and the enhanced gene expression was most pronounced at late time points. Compared to wild-type mice, S534A mice displayed increased mortality after injection with LPS. Increased NF-kappaB signaling in the S534A mice was at least in part explained by the increased stability of the S534A p65 protein compared to that of the Ser(534)-phosphorylated wild-type protein. Together, our results suggest that Ser(534) phosphorylation of p65 in mice (and, by extension, Ser(536) phosphorylation of human p65) is not required for its nuclear translocation, but instead inhibits NF-kappaB signaling to prevent deleterious inflammation. PMID- 27555663 TI - Frequency of KLK3 gene deletions in the general population. AB - Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population. Methods The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample ( n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population. Results Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis. Conclusions We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring. PMID- 27555664 TI - Elevated fasting and postprandial C-terminal telopeptide after Roux-en-Y gastric bypass. AB - Background Roux-en-Y gastric bypass increases circulating bile acid concentrations, known mediators of postprandial suppression of markers of bone resorption. Long-term data, however, indicate that Roux-en-Y gastric bypass confers an increased risk of bone loss on recipients. Methods Thirty-six obese individuals, median age 44 (26-64) with median body mass index at baseline of 42.5 (40.4-46) were studied before and 15 months after Roux-en-Y gastric bypass. After an overnight fast, patients received a 400 kcal mixed meal. Blood samples were collected premeal then at 30-min periods for 120 min. Pre and postmeal samples were analysed for total bile acids, parathyroid hormone and C-terminal telopeptide. Results Body weight loss post Roux-en-Y gastric bypass was associated with a median 4.9-fold increase in peak postprandial total bile acid concentration, and a median 2.4-fold increase in cumulative food evoked bile acid response. Median fasting parathyroid hormone, postprandial reduction in parathyroid hormone and total parathyroid hormone release over 120 min remained unchanged after surgery. After surgery, median fasting C-terminal telopeptide increased 2.3-fold, peak postprandial concentrations increased 3.8-fold and total release was increased 1.9-fold. Conclusions Fasting and postprandial total bile acids and C-terminal telopeptide are increased above reference range after Roux en-Y gastric bypass. These changes occur in spite of improved vitamin D status with supplementation. These results suggest that post-Roux-en-Y gastric bypass increases in total bile acids do not effectively oppose an ongoing resorptive signal operative along the gut-bone axis. Serial measurement of C-terminal telopeptide may be of value as a risk marker for long-term skeletal pathology in patients post Roux-en-Y gastric bypass. PMID- 27555665 TI - Best practice guidelines on first-line laboratory testing for porphyria. AB - The porphyrias are disorders of haem biosynthesis which present with acute neurovisceral attacks or disorders of sun-exposed skin. Acute attacks occur mainly in adults and comprise severe abdominal pain, nausea, vomiting, autonomic disturbance, central nervous system involvement and peripheral motor neuropathy. Cutaneous porphyrias can be acute or chronic presenting at various ages. Timely diagnosis depends on clinical suspicion leading to referral of appropriate samples for screening by reliable biochemical methods. All samples should be protected from light. Investigation for an acute attack: * Porphobilinogen (PBG) quantitation in a random urine sample collected during symptoms. Urine concentration must be assessed by measuring creatinine, and a repeat requested if urine creatinine <2 mmol/L. * Urgent porphobilinogen testing should be available within 24 h of sample receipt at the local laboratory. Urine porphyrin excretion (TUP) should subsequently be measured on this urine. * Urine porphobilinogen should be measured using a validated quantitative ion-exchange resin-based method or LC-MS. * Increased urine porphobilinogen excretion requires confirmatory testing and clinical advice from the National Acute Porphyria Service. * Identification of individual acute porphyrias requires analysis of urine, plasma and faecal porphyrins. Investigation for cutaneous porphyria: * An EDTA blood sample for plasma porphyrin fluorescence emission spectroscopy and random urine sample for TUP. * Whole blood for porphyrin analysis is essential to identify protoporphyria. * Faeces need only be collected, if first-line tests are positive or if clinical symptoms persist. Investigation for latent porphyria or family history: * Contact a specialist porphyria laboratory for advice. Clinical, family details are usually required. PMID- 27555666 TI - The investigation of children and adolescents with abnormalities of pubertal timing. AB - Concerns with pubertal development are common and can cause considerable distress to patients and their carers. Many presentations reflect normal variations of pubertal timing and primarily require reassurance, although patients may opt for interventions. Other presentations need active management to avoid significant adverse effects on growth and psychosocial development. All should undergo careful assessment, particularly as some children or adolescents presenting with abnormalities in pubertal timing may have serious pathology which requires urgent investigations and treatment. This review describes the appropriate investigations and their interpretation for young people presenting with disorders in pubertal timing. PMID- 27555667 TI - Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients. AB - Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP 9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process. PMID- 27555668 TI - Degraded Impairment of Emotion Recognition in Parkinson's Disease Extends from Negative to Positive Emotions. AB - Because of dopaminergic neurodegeneration, patients with Parkinson's disease (PD) show impairment in the recognition of negative facial expressions. In the present study, we aimed to determine whether PD patients with more advanced motor problems would show a much greater deficit in recognition of emotional facial expressions than a control group and whether impairment of emotion recognition would extend to positive emotions. Twenty-nine PD patients and 29 age-matched healthy controls were recruited. Participants were asked to discriminate emotions in Experiment 1 and identify gender in Experiment 2. In Experiment 1, PD patients demonstrated a recognition deficit for negative (sadness and anger) and positive faces. Further analysis showed that only PD patients with high motor dysfunction performed poorly in recognition of happy faces. In Experiment 2, PD patients showed an intact ability for gender identification, and the results eliminated possible abilities in the functions measured in Experiment 2 as alternative explanations for the results of Experiment 1. We concluded that patients' ability to recognize emotions deteriorated as the disease progressed. Recognition of negative emotions was impaired first, and then the impairment extended to positive emotions. PMID- 27555669 TI - Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients. AB - Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID- 27555671 TI - Celebrity endorsements in medicine: who should be held liable? PMID- 27555670 TI - Effect of Interferon-gamma on the Basal and the TNFalpha-Stimulated Secretion of CXCL8 in Thyroid Cancer Cell Lines Bearing Either the RET/PTC Rearrangement Or the BRAF V600e Mutation. AB - CXCL8 displays several tumor-promoting effects. Targeting and/or lowering CXCL8 concentrations within the tumor microenvironment would produce a therapeutic benefit. Aim of this study was to test the effect of IFNgamma on the basal and TNFalpha-stimulated secretion of CXCL8 in TCP-1 and BCPAP thyroid cancer cell lines (harboring RET/PTC rearrangement and BRAF V600e mutation, resp.). Cells were incubated with IFNgamma (1, 10, 100, and 1000 U/mL) alone or in combination with TNF-alpha (10 ng/mL) for 24 hours. CXCL8 and CXCL10 concentrations were measured in the cell supernatants. IFNgamma inhibited in a dose-dependent and significant manner both the basal (ANOVA F: 22.759; p < 0.00001) and the TNFalpha stimulated (ANOVA F: 15.309; p < 0.00001) CXCL8 secretions in BCPAP but not in TPC-1 cells (NS). On the other hand, IFNgamma and IFNgamma + TNF-alpha induced a significant secretion of CXCL10 in both BCPAP (p < 0.05) and TPC-1 (p < 0.05) cells. Transwell migration assay showed that (i) CXCL8 increased cell migration in both TPC-1 and BCPAP cells; (ii) IFNgamma significantly reduced the migration only of BCPAP cells; and (iii) CXCL8 reverted the effect of IFNgamma. These results constitute the first demonstration that IFNgamma inhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line. PMID- 27555672 TI - Current trends in kidney transplantation in India. PMID- 27555673 TI - Renal transplantation in 2016. PMID- 27555674 TI - The development and current status of Intensive Care Unit management of prospective organ donors. AB - INTRODUCTION: Despite continuous advances in transplant medicine, there is a persistent worldwide shortage of organs available for donation. There is a growing body of research that supports that optimal management of deceased organ donors in Intensive Care Unit can substantially increase the availability of organs for transplant and improve outcomes in transplant recipients. METHODS: A systematic literature review was performed, comprising a comprehensive search of the PubMed database for relevant terms, as well as individual assessment of references included in large original investigations, and comprehensive society guidelines. RESULTS: In addition to overall adherence to catastrophic brain injury guidelines, optimization of physiologic state in accordance with established donor management goals (DMGs), and establishment of system-wide processes for ensuring early referral to organ procurement organizations (OPOs), several specific critical care management strategies have been associated with improved rates and outcomes of renal transplantation from deceased donors. These include vasoactive medication selection, maintenance of euvolemia, avoidance of hydroxyethyl starch, glycemic control, targeted temperature management, and blood transfusions if indicated. CONCLUSIONS: Management of deceased organ donors should focus first on maintaining adequate perfusion to all organ systems through adherence to standard critical care guidelines, early referral to OPOs, and family support. Furthermore, several specific DMGs and strategies have been recently shown to improve both the rates and outcomes of organ transplantation. PMID- 27555675 TI - The development and current status of minimally invasive surgery to manage urological complications after renal transplantation. AB - INTRODUCTION: In the past, urological complications after renal transplantation were associated with significant morbidity. With the development and application of endourological procedures, it is now possible to manage these cases with minimally invasive techniques. MATERIALS AND METHODS: A MEDLINE search for articles published in English using key words for the management of urological complications after renal transplantation was undertaken. Forty articles were selected and reviewed. RESULTS: The incidence of urological complications postrenal transplantation was reported to be 2-13%. Ureteric leaks occurred in up to 8.6%, and 55% were managed endourologically. The incidence of lymphocele was as high as 20%, and less that 12% of the cases required treatment. Ureteric stricture was the most common complication, and endourological management was successful in 50-70%. The occurrence of complicated vesicoureteral reflux was 4.5%, and 90% of low-grade reflux cases were successfully treated with deflux injections. Stones and obstructive voiding dysfunction occurred in about 1% of kidney transplant recipients. CONCLUSION: Minimally invasive techniques have a critical role in the management of urological complications after renal transplantation. Urinary leakage should be managed with complete decompression. Percutaneous drainage should be the first line of treatment for lymphocele that is symptomatic or causing ureteric obstruction. Laparoscopic lymphocele deroofing is successful in aspiration-resistant cases. Deflux is highly successful for the management of complicated low-grade kidney transplant reflux. The principles of stone management in a native solitary kidney are applied to the transplanted kidney. Early identification and treatment of bladder outlet obstruction after renal transplantation can prevent urinary leakage and obstructive uropathy. PMID- 27555676 TI - The role of the pharmacist in the management of kidney transplant recipients. AB - Pharmacists may play a key role on the multidisciplinary transplant team. This article describes the development and current status of pharmacists in the management of transplant recipients in the United States. Traditionally, pharmacists played an important support role in transplant medicine. This role has been expanded to include direct patient care for the avoidance, detection, and/or treatment of side effects from the polypharmacy necessary in the management of these complex patients. Pharmacists provide pre- and post transplant education to transplant recipients to enhance adherence to complicated medical regimens and thereby reduce readmission to hospital and unscheduled, costly visits to urgent care centers and/or hospital emergency departments. PMID- 27555677 TI - Assessment of the performance of Partin's nomogram (2007) in contemporary Indian cohort. AB - INTRODUCTION: Partin's nomogram is an important prognostic tool to predict adverse pathological features for clinically localized prostate carcinoma. This tool is widely used by both radiation and surgical oncologists for pre intervention counseling, treatment planning, and predicting the possible need for adjuvant treatment. However, the model is derived from a Western population with typical characteristics of prostate cancer in a prostate-specific antigen (PSA) screened population. Therefore, this study was conducted to assess the performance of the Partin's nomogram as applied to an Indian cohort by assessing the discrimination and calibration properties. METHODS: A retrospective review of 282 patients treated with robotic radical prostatectomy from 2010 to 2015 was conducted. Partin tables (year 2007) were used to calculate the predicted probabilities for lymph node invasion (LNI), seminal vesicle invasion (SVI), and extraprostatic extension (EPE). The discrimination properties were assessed using the receiver operating characteristic (ROC) curves. Calibration of the model was done to show the relationship between predicted and observed values. RESULTS: The mean age of the patients was 64.3 years. Most (59.4%) were clinical T2 disease. Patients with PSA >10 ng/ml comprised 60% of the population. ECE, SVI, and LNI were present in 39.2%, 22%, and 11% of cases, respectively. ROC analysis revealed area under curve values for EPE, SVI, and LNI of 68%, 67.5%, and 71.2%, respectively. Calibration plot suggested that the Partin tables under-predicted the risk whenever the values of predicted risk were more than 26%, 3%, and 1% for EPE, SVI, and LNI, respectively, and over predicted when the risk was lower. CONCLUSION: Our data show that Partin's tables, despite having fair discrimination properties, do not accurately predict LNI, SVI, and ECE across the entire range of predicted values in a contemporary Indian cohort. PMID- 27555678 TI - Impact of assistant surgeon on outcomes in robotic surgery. AB - INTRODUCTION: It is believed that the outcomes of robotic surgery depends not only on the experience of the console surgeon but also the patient-side assistant. However, objective data supporting it is lacking. The aim of this study was to objectively determine change in operative outcomes with increasing experience of patient-side assistant. MATERIALS AND METHODS: We performed a retrospective analysis of 222 urologic robotic procedures performed by two teams of surgeon-assistant and split the data into two chronological halves according to date of surgery. We considered that the assistant was inexperienced in the 1(st) half and had become experienced by the 2(nd) half, and we compared mean operative time and blood loss between these two halves of his experience. RESULTS: We observed that with increasing experience of the assistant, the mean operative time reduced from 138.06 to 124.32 min (P = 0.001) and mean blood loss decreased from 191.93 to 187.61 ml (P = 0.57). On subset analysis, a consistent trend of reduction in the mean operative time was noted for both the assistants separately and for all surgical procedures included in the analysis. Maximum reduction was noted for pyeloplasty which was the most commonly performed surgery. The mean blood loss had a varied relation to the experience of the assistant and did not reach statistical significance in either direction. CONCLUSIONS: With increasing experience of the patient-side surgeon, the mean operative time for all robotic procedures showed a consistent trend of reduction across all types of surgery with greater reduction for commonly performed procedures. PMID- 27555679 TI - Dosimetric correlation of acute and late toxicities in high-risk prostate cancer patients treated with three-dimensional conformal radiotherapy followed by intensity modulated radiotherapy boost. AB - INTRODUCTION: In prostate cancer, higher radiation doses are often related to higher local control rates. However, the clinical effect of these higher doses on normal tissue toxicities is generally overlooked. We dosimetrically analyze sequential intensity modulated radiotherapy (IMRT) plans in high-risk prostate cancer patients and correlate them with acute and late normal tissue toxicities. MATERIALS AND METHODS: Twenty-five high-risk prostate cancer patients were planned with three-dimensional conformal radiotherapy to a dose of 50 Gy delivered in 25 fractions in 5 weeks, followed by seven-field IMRT boost, to a dose of 24 Gy delivered in 12 fractions in 2.5 weeks, along with hormonal therapy. Acute and late toxicities were analyzed using Radiation Therapy Oncology Group toxicity criteria. Student's t-test was used for correlating doses received by normal tissues with toxicity grade. Five-year disease-free survival (DFS) and biochemical relapse-free survival (RFS) were evaluated using Kaplan-Meier analysis. RESULTS: Median follow-up of patients was 65 months. Of 25 patients, two developed acute Grade 2 rectal toxicity. Only 1 patient developed acute Grade 2 bladder toxicity. Late Grade 2 and 3 rectal toxicity was seen in 2 and 1 patient, respectively. Late Grade 2 and 3 bladder toxicity was seen in 1 patient each. Grade 2 or more acute rectal toxicity correlated significantly with rectal volume receiving >70 Gy (P = 0.04). The 5-year DFS and biochemical RFS was 70.2% and 79.2%, respectively. One patient failed locally and seven failed at distant sites. CONCLUSION: Sequential IMRT with a dose of 74 Gy and maximum androgen blockade is well tolerated in high-risk patients in Indian setup with adequate control rates. PMID- 27555680 TI - Impact of changing trends in technique and learning curve on outcome of hypospadias repair: An experience from tertiary care center. AB - INTRODUCTION: Apart from numerous clinical factors, surgical experience and technique are important determinants of hypospadias repair outcome. This study was aimed to evaluate the learning curve of hypospadias repair and the impact of changing trends in surgical techniques on the success of primary hypospadias repair. MATERIALS AND METHODS: We retrospectively analyzed of data of 324 patients who underwent primary repair of hypospadias between January 1997 and December 2013 at our center. During the initial 8 years, repairs were performed by multiple 5 different urologists. From 2005 onwards, all procedures were performed by a single urologist. The study cohorts was categorized into three groups; Group I, surgeries performed between 1997-2004 by multiple surgeons, Group II, between 2005-2006 during the initial learning curve of a single surgeon, and Group III, from 2007 onwards after completion of the learning curve of the single surgeon. The groups were compared in respect to surgical techniques, overall success and complications. RESULTS: Overall 296 patients fulfilled the inclusion criterion, 93 (31.4%), 50 (16.9%), and 153 (51.7%) in Group I, II, and III, respectively. Overall success was achieved in 60 (64.5%), 32 (64%), and 128 (83.7%) patients among the three groups respectively (P < 0.01). Nineteen (20.4%), 20 (40%), and 96 (62.7%) patients underwent tubularized incised plate repair in Group I, II, and III, with successful outcome in 12 (63.2%), 15 (75%), and 91 (94.8%) patients, respectively (P < 0.01). The most common complication among all groups was urethrocutaneous fistula, 20 (21.5%) in Group I, 11 (22%) in Group II, and 17 (11.1%) in Group III. CONCLUSION: There is a learning curve for attaining surgical skills in hypospadias surgery. Surgeons dedicated for this surgery provide better results. Tubularized incised plate urethroplasty appear promising in both distal and proximal type hypospadias. PMID- 27555681 TI - Follow-up imaging after pediatric pyeloplasty. AB - INTRODUCTION: The duration, methods and frequency of radiographic follow-up after pediatric pyeloplasty is not well-defined. We prospectively evaluated a cohort of children undergoing pyeloplasty to determine the method for follow-up. METHODS: Between 2000 and 2008, children undergoing pyeloplasty for unilateral ureteropelvic junction obstruction were evaluated for this study. All patients were evaluated preoperatively with protocol ultrasound (USG) and diuretic renal scan (RS). On the basis of preoperative split renal function (SRF), these patients were divided into four groups - Group I: SRF > 40%, Group II: SRF 30 39%, Group III: SRF 20-29%, and Group IV: SRF 10-19%. In follow-up, USG and RS were done at 3 months and repeated at 6 months, 1 year, and then yearly after surgery for a minimum period of 5 years. Improvement, stability, or worsening of hydronephrosis was based on the changes in anteroposterior (AP) diameter of pelvis and caliectasis on USG. Absolute increase in split renal function (SRF) >5% was considered significant. Failure was defined as increase in AP diameter of pelvis and decrease in cortical thickness on 3 consecutive USG, t1/2 >20 min with obstructive drainage on RS and/or symptomatic patient. RESULTS: 145 children were included in the study. Their mean age was 3.26 years and mean follow-up was 7.5 years. Pre- and post-operative SRF remain unchanged within 5% range in 35 of 41 patients (85%) in Group I. While 9 of 20 patients (45%) in Group II, 23 of 50 patients (46%) in Group III, and 14 of 34 patients (41%) in Group IV exhibited changes >5% after surgery. 5 patients failed, 2 in Group III, and 3 in Group IV. None of the patients deteriorated in Group I and II. CONCLUSION: After pyeloplasty in children with a baseline split GFR >30%, if a diuretic renogram and USG performed 3 months postoperatively shows nonobstructive drainage with t1/2 <20 min and decreased hydronephrosis, no further follow-up is required. PMID- 27555682 TI - Comment on: Kumar et al. Follow-up imaging after pediatric pyeloplasty. Indian J Urol, 2016;32:221-226. PMID- 27555683 TI - Concomitant repair of stress urinary incontinence with proximal urethrovaginal fistula: Our experience. AB - INTRODUCTION: Proximal urethrovaginal fistula (UVF) located close to the bladder neck may cause extensive sphincter damage and is usually associated with continuous incontinence, which may mask the associated stress urinary incontinence (SUI). Simultaneous correction of SUI avoids a second surgery for SUI, which needs dissection in ischemic fields and carries a high risk of failure. The aim of this study is to describe our technique of concomitant repair of SUI with proximal UVF and our results. METHODS: Between July 2010 and August 2014, 14 patients underwent UVF repair in Jackknife position by the interposition of a Martius flap and simultaneous correction of SUI by modified McGuire pubovaginal autologous fascial sling. The procedure was carried out a minimum of 3 months of presentation and after detailed preoperative evaluation. RESULTS: After a mean follow-up of 28 months, all 14 patients were continent. None of the patients developed recurrence of the UVF. Two patients presented with retention immediately after catheter removal and clean intermittent catheterization training was given to both of them. Two patients became pregnant during the follow-up period and were advised cesarean section near term. CONCLUSIONS: Repair of proximal UVF and correction of SUI can be performed in the same session to avoid the operation in an ischemic field. PMID- 27555684 TI - Grading of complications of transurethral resection of bladder tumor using Clavien-Dindo classification system. AB - INTRODUCTION: Clavien-Dindo classification system is used for grading complications of various oncological, renal, and endourological procedures. We applied this system for grading the severity of perioperative complications in patients undergoing transurethral resection of bladder tumor (TURBT) and identify parameters predicting these complications. MATERIALS AND METHODS: Data of 984 patients who underwent TURBT from 2006 to 2014 were included in this study. All data was retrospectively collected and analyzed for complications occurring within the first postoperative month. All complications were classified according to the five grades of modified CCS (.Clavien classification system). RESULTS: A total of 172 complications were observed in 138 patients. Majority were low grade complications (Grade 1 [77.3%] and Grade 2 [12.7%]). Higher grade complications were rare (Grade 3 [6.4%] and Grade 4 [3.0%]). There was one death (Grade 5 0.6%), with an overall mortality rate of 0.1%. The incidence of complications was significantly greater for age >60 years, baseline serum creatinine >1.4 mg/dl, size of tumor >4 cm, tumor located at dome, resection time >60 min, incomplete resection and if surgery performed by a resident urologist. CONCLUSIONS: Clavien Dindo classification system can be easily applied to grade the complications of TURBT, and it is easily reproducible. We observed that TURBT was a safe procedure. Majority of complications were Grade 1-2 (90%) and Grade 3-5 were rare (10%). Postoperative bleeding is the most common complication. A greater rate of complications of TURBT was associated with patient age, size of tumor, location of tumor, surgeon experience, resection time, and completion of tumor resection. PMID- 27555685 TI - Feasibility of robotic radical prostatectomy for medication refractory chronic prostatitis/chronic pelvic pain syndrome: Initial results. AB - Four patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), met criteria for National Institute of Health (NIH) Category III prostatitis, failed multiple medicinal treatments and underwent robotic radical prostatectomy (RRP). Median operative time (range): 157 (127-259) min. Validated functional questionnaires responses and NIH CP symptom index (NIH-CPSI) score were collected for each patient's status at different time points pre- and post operatively. Median decreases (range) were: International Prostate Symptom Score 14 (1-19); Sexual Health Inventory for Men - 6 (-14-22); and NIH-CPSI total - 23.5 (13-33). Median length of follow-up (range) was 34 (24-43) months. RRP appears to be an option for carefully selected patients with medication refractory CP/CPPS who understand that baseline sexual function may not be restored postoperatively. PMID- 27555686 TI - Herpes zoster reactivation after extracorporeal shock wave lithotripsy: A case report. AB - Herpes zoster is a reactivated varicella-zoster virus (VZV) infection of the sensory nerve ganglion, peripheral nerve, and its branches. Mechanical trauma to the nervous system can reactivate VZV. It is well known that extracorporeal shock wave lithotripsy (SWL) can produce mechanical damage to the tissue. We report a rare case of herpes zoster reactivation after SWL for treatment of 1.2 cm size renal stone in a 63-year-old male patient. PMID- 27555687 TI - Rare presentation of urachal adenocarcinoma with skip metastasis to colon. AB - Urachal carcinoma is a rare malignancy constituting <1% of bladder malignancies. The disease arises from a malignant transformation of rests of enteric epithelium in the urachus. Most common sites of metastasis are lung, liver, and bone. We report a postoperative case of urachal carcinoma presenting with distant metastasis to lung and skip lesions in colon. As both urachal and colon carcinoma share common histopathological features, most of the literature suggested using chemotherapy regimens similar to those recommended for colon malignancies. There are no randomized trials till date regarding the management of urachal adenocarcinomas except for the primary treatment being surgery. PMID- 27555688 TI - Cryptorchid testis with torsion: Inguinoscrotal whirlpool sign. AB - Non contrast helical computed tomography (CT) study of the abdomen is frequently performed in evaluation of suspected ureteric colic. We present CT images of a young adult male patient who had torsion of an undescended, non-neoplastic testis and describe the "Inguinoscrotal whirlpool sign on CT". PMID- 27555689 TI - Primary emphysematous adrenal hydatid: Unusual site for presentation with rare pathology. AB - Hydatid disease of the adrenal gland is uncommon. We present images and description a case of emphysematous hydatid cyst of the adrenal gland that had an unfavourable intraoperative outcome. PMID- 27555690 TI - Hematuria among dengue patients: A note on observation. PMID- 27555691 TI - Impact of malnutrition on pediatric risk of mortality score and outcome in Pediatric Intensive Care Unit. AB - OBJECTIVES: This study was done to determine the effect of malnutrition on mortality in Pediatric Intensive Care Unit (PICU) and on the pediatric risk of mortality (PRISM) scoring. SUBJECTS AND METHODS: This was a prospective study done over 1 year. There were total 400 patients (1 month 14 years), who were divided into cases with weight for age <3(rd) centile and controls with >=3(rd) centile of WHO charts. Cases were subdivided into mild/moderate (61-80% of expected weight for age) and severe malnutrition (<60%). RESULTS: Out of total, 38.5% patients were underweight, and malnutrition was more in infancy, 61/104, i.e. 58.5% (P - 0.003). There was no significant difference in vitals at admission. Cases needed prolonged mechanical ventilation (P - 0.0063) and hospital stay (P - 0.0332) compared to controls. Mean and median PRISM scores were comparable in both the groups, but mortality was significantly higher in severely malnourished (P value 0.027). CONCLUSION: Severe malnutrition is independently associated with higher mortality even with similar PRISM score. There is need to give an additional score to children with weight for age <60% of expected. PMID- 27555692 TI - Characteristics and mortality of elderly patients admitted to the Intensive Care Unit of a district hospital. AB - AIM: To study all the elderly patients (>=75 years) who were admitted in an Intensive Care Unit (ICU) of a Spanish hospital and identify factors associated with mortality. PATIENTS AND METHODS: A retrospective, observational data collected prospectively in patients >=75 years recruited from the ICU in the period of January 2004 to December 2010. RESULTS: During the study period, 1661 patients were admitted to our unit, of whom 553 (33.3%) were older than 75 years. The mean age was 79.9 years, 317 (57.3%) were male, and the overall in-hospital mortality was 94 patients (17% confidence interval 14-20.3%). When comparing patients who survived to those who died, we found significant differences in mean age (P = 0.001), Acute Physiologic Assessment and Chronic Health Evaluation II and Simplified Acute Physiology Scoring II (SAPS II) on admission (P < 0.0001, postoperative patients (P = 0.001), and need for mechanical ventilation (P < 0.0001). Comparing age groups, we found statistically significant differences in SAPS II (P = 0.007), diagnosis of non-ST-segment elevation myocardial infarction (P = 0.014), complicated postoperative period (P = 0.001), and pacemaker (P = 0.034). Mortality between the groups was statistically significant (P = 0.004). The survival between the group of 65 and 74 years and patients >75 years was not significant (P = 0.1390). CONCLUSIONS: The percentage of elderly patients in our unit is high, with low mortality rates. The age itself is not the sole determinant for admission to the ICU and other factors should be taken into account. PMID- 27555693 TI - A comparative cost analysis of polytrauma and neurosurgery Intensive Care Units at an apex trauma care facility in India. AB - CONTEXT: Although Intensive Care Units (ICUs) only account for 10% of the hospital beds, they consume nearly 22% of the hospital resources. Few definitive costing studies have been conducted in Indian settings that would help determine appropriate resource allocation. AIM: The aim of this study was to evaluate and compare the cost of intensive care delivery between multispecialty and neurosurgery ICUs at an apex trauma care facility in India. MATERIALS AND METHODS: The study was conducted in a polytrauma and neurosurgery ICU at a 203 bedded Level IV trauma care facility in New Delhi, India, from May 1, 2012 to June 30, 2012. The study was cross-sectional, retrospective, and record-based. Traditional costing was used to arrive at the cost for both direct and indirect cost estimates. The cost centers included in the study were building cost, equipment cost, human resources, materials and supplies, clinical and nonclinical support services, engineering maintenance cost, and biomedical waste management. STATISTICAL ANALYSIS: Statistical analysis was performed by Fisher's two tailed t test. RESULTS: Total cost/bed/day for the multispecialty ICU was Rs. 14,976.9/- and for the neurosurgery ICU, it was Rs. 14,306.7/-, workforce constituting nearly half of the expenditure in both ICUs. The cost center wise and overall difference in the cost among the ICUs were statistically significant. CONCLUSIONS: Quantification of expenditure in running an ICU in a trauma center would assist health-care decision makers in better allocation of resources. Although multispecialty ICUs are more cost-effective, other factors will also play a role in defining the kind of ICU that needs to be designed. PMID- 27555694 TI - Early demographic and clinical predictors of developing acute kidney injury in snake bite patients: A retrospective controlled study from an Indian tertiary care hospital in North Eastern Uttar Pradesh India. AB - AIMS: This study was conducted retrospectively to define early demographic and clinical predictors for acute kidney injury (AKI) among snake bite patients at the time of hospital admission. MATERIALS AND METHODS: We analyzed 138 cases with a poisonous snake bite. Patients were classified into two groups according to the presence and absence of AKI. The data regarding clinical features and demographic profile of these patients were collected from the hospital records in a prestructured pro forma and statistically compared. RESULTS: Of the 138 patients of venomous snake bite, 62 developed AKI (44.92%). Patients who developed AKI were older in age. Moreover, prolonged bite to anti-snake venom (ASV) time had a significant relationship in developing AKI (P < 0.05). Among the clinical features, there was an independent positive association of AKI with abdomen pain, tenderness and vomiting, cellulitis, bleeding tendencies, myalgia, and black or brown urine (P < 0.05). Neurological features were inversely associated with renal involvement. CONCLUSION: We found that marked abdominal pain, tenderness and vomiting, myalgia, black or brown urine, bite site cellulitis, bleeding tendencies, and prolonged (>2 h) bite to ASV time were significantly associated with the development of AKI in snake bite patients. PMID- 27555695 TI - Complications of tracheal intubation in critically ill pediatric cancer patients. AB - BACKGROUND AND AIMS: The oncologists are treating cancer more aggressively, leading to increase in number of pediatric admissions to the ICU. Due to anatomical and physiological differences, pediatric patients are at high risk of complications during intubation. We evaluated the incidence of complications during intubations in pediatric patients in our ICU. SUBJECTS AND METHODS: We performed retrospective analysis of complications occurring during intubation in 42 pediatric patients. All intubations were orotracheal. We recorded number of attempts at intubation, need for use of intubation adjuncts and complications during laryngoscopy and intubation. The incidence of difficult intubation, hypoxia, and severe cardiovascular collapse was also noted. RESULTS: Complications occurred during 13 (31%) intubations. Hypoxia and severe cardiovascular collapse occurred in during 7 (16.7%) intubations each, while 4 patients (9.5%) (n=4) had cardiac arrest during intubation. Thirty three (78.6%) intubations were successful in first attempt and difficult intubation was recorded in 4 patients. CONCLUSION: Critically ill pediatric cancer patients have a high rate of complications during intubation. PMID- 27555697 TI - The role of C-reactive protein as a diagnostic predictor of sepsis in a multidisciplinary Intensive Care Unit of a tertiary care center in Nepal. AB - AIM: C-reactive protein (CRP) is a commonly used biomarker of sepsis, the leading cause of mortality in Intensive Care Units (ICUs). However, sufficient data are still lacking to strongly recommend it in clinical practice. The present study is aimed to find out its reliability in diagnosing sepsis. MATERIALS AND METHODS: CRP was measured in ICU-admitted patients with systemic inflammatory response syndrome and compared using a cutoff of 50 mg/L with the gold standard for diagnosing sepsis, taken as isolation of organism from a suspected source of infection or the Centers for Disease Control criteria for clinical sepsis. RESULTS: CRP had a sensitivity and specificity of 84.3% and 46.15%, respectively. Area under the receiver operating characteristics curve was calculated to be 0.683 (+/-0.153, P < 0.05). The cutoff value with the best diagnostic accuracy was found to be 61 mg/L. CONCLUSION: CRP is a sensitive marker of sepsis, but it is not specific. PMID- 27555698 TI - Tombs of Aspergillus: A missed cause of recurrent respiratory infections in allergic bronchopulmonary aspergillosis. AB - Broncholithiasis is an often overlooked condition and has been associated with symptoms such as cough, hemoptysis, and recurrent respiratory infections. The most common mechanism of a broncholith formation is the enlargement and subsequent erosion of a lymph node into an adjacent airway. Here, we describe this entity in a patient with advanced allergic bronchopulmonary aspergillosis, with chronic hypercapnic respiratory failure, and with frequent infective exacerbations. These frequent exacerbations were initially attributed to the poor lung function of the patient and the inability to cough out the secretions. The diagnosis of broncholithiasis was eventually established on bronchoscopy, when the patient was intubated and mechanically ventilated. In this patient, the mixed broncholiths were not associated with mediastinal lymphadenopathy and with biopsy showing Aspergillus with no lymph node tissue indicating its bronchial origin. A high index of suspicion should be kept in patients with recurrent infective exacerbations of pulmonary diseases, especially when computed tomography images show calcifications in the vicinity of airways even in the absence of lymphadenopathy, as most of these can be treated with routine bronchoscopic interventions. PMID- 27555696 TI - The incidence of deep venous thrombosis in high-risk Indian neurosurgical patients: Need for early chemoprophylaxis? AB - INTRODUCTION: Deep venous thrombosis (DVT) is thought to be less common in Asians than in Caucasian population. The incidence of DVT in high-risk groups, especially the neurosurgical (NS) patients, has not been well studied. This leaves no firm basis for the start of early prophylactic anticoagulation within first 5 postoperative days in Indian NS patients. This is a prospective observational study to determine the early occurrence of DVT in the NS patients. PATIENTS AND METHODS: We screened 137 consecutive high-risk NS patients based on inclusion and exclusion criteria. The femoral veins were screened using Doppler ultrasound on day 1, 3, and 5 of admission into the NS Intensive Care Unit (ICU) at tertiary center from South India. RESULTS: Among 2887 admissions to NICU 147 patients met inclusion criteria. One hundred thirty seven were screened for DVT. There was a 4.3% (6/137) incidence of DVT with none of the six patients having signs or symptoms of pulmonary embolism. Among the risk factors studied, there was a significant association with femoral catheterization and a probable association with weakness/paraparesis/paraplegia. The mortality in the study group was 10.8% with none attributable to DVT or pulmonary embolism. CONCLUSION: There is a low incidence of DVT among the high risk neurosurgical population evaluated within the first 5 days of admission to NICU, limiting the need for early chemical thrombo-prophylaxis in these patients. With strict protocols for mechanical prophylaxis with passive leg exercise, early mobilization and serial femoral Doppler screening, heparin anticoagulation can be restricted within the first 5 days of ICU admission in high risk patients. PMID- 27555699 TI - Systemic thrombolysis with recombinant tissue plasminogen activator for acute life-threatening Blalock-Taussig shunt obstruction. AB - Modified Blalock-Taussig shunt (mBTS) obstruction can be life-threatening, especially when it represents the only source of pulmonary blood flow. Current therapeutic options to reverse obstruction include surgical shunt revision/replacement, interventional endovascular procedures including balloon angioplasty and/or stent placement, and a combination of local and systemic thrombolytic therapy. We report two cases of acute mBTS thrombosis successfully treated with systemic recombinant tissue plasminogen activator in infants convalescing after cardiac surgery when the clinical status and resources precluded traditionally described rescue therapies. PMID- 27555700 TI - Acute intermittent porphyria: A critical diagnosis for favorable outcome. AB - Acute intermittent porphyria (AIP) is an inherited metabolic disorder characterized by the accumulation of toxic metabolites of the heme pathway. It rarely presents in the prepubertal age group. AIP often presents with nonspecific and nonlocalizing symptoms. Moreover, several commonly used medications and stress states are known to precipitate an attack. We present the case of a previously healthy 5 years female who was diagnosed as acute central nervous system infection/inflammation at admission. It was the presence of red flags that led to a correct diagnosis. Besides supportive management, a dedicated search for intravenous hemin (chemically heme arginate, aminolevulinic acid synthase inhibitor, and drug of choice) was attempted. Unexpected help was rendered by doctors from a medical college in Gujarat, and two ampoules could be obtained. The patient received three doses of intravenous hemin; however, she succumbed later. This case is presented for the diagnostic and therapeutic challenges faced in developing countries. PMID- 27555701 TI - Hospital curtains: An undermined source of nosocomial infections. PMID- 27555702 TI - Dealing with the neglected public health issue of drowning in low-resource settings. PMID- 27555703 TI - Calculating incidence and prognosis in a prospective study. PMID- 27555704 TI - Odontogenic-related sepsis. PMID- 27555705 TI - Erratum: Yakson touch as a part of early intervention in the Neonatal Intensive Care Unit: A systematic narrative review. AB - [This corrects the article on p. 349 in vol. 20, PMID: 27390459.]. PMID- 27555706 TI - Demographic and Clinical Features of Pediatric Uveitis at a Tertiary Referral Center in Iran. AB - PURPOSE: To determine the clinical features and distribution of uveitis in the pediatric age group at a referral eye care center in Shiraz, South Iran. MATERIALS AND METHODS: All new cases of uveitis in patients 18-year-old or younger referred from January 2007 to December 2013 were enrolled in this study. The patient underwent a complete history of systemic and ocular diseases, comprehensive ophthalmic examination. Patients were classified according to the International Uveitis Study Group definitions. The definitive diagnosis was based on clinical manifestations and laboratory investigations. RESULTS: Seventy-seven eyes (54 patients) comprised the study sample. The mean age at the onset of uveitis was 12.5 years. The female-to-male ratio was 1.25. Anterior uveitis was the most frequent anatomical location (40.7%), followed by intermediate uveitis (33.3%), posterior uveitis (18.5%), and panuveitis (7.5%). Seventy-four percent of patients presented with chronic uveitis. Noninfectious uveitis (81.5%) was the most frequent etiology. Thirty-seven percent of patients had a specific diagnosis for uveitis, and 63% were classified as idiopathic cases. Toxocariasis was the most common infectious cause. Associated systemic diseases were present in 14.8% of patients. The most frequent systemic disease was juvenile idiopathic arthritis in 9.2% of patients. Complications occurred in 66 (85.5%) of affected eyes. The most common complications were posterior synechia (20.7%), cataract (18.8%), and cystoid macular edema (12.9%). CONCLUSIONS: Uveitis in the majority of children had an insidious onset and was chronic. Over half the patients had a specific diagnosis. Idiopathic cases were more common in the intermediate uveitis group. PMID- 27555707 TI - Lack of Correlation Between Diabetic Macular Edema and Thickness of the Peripapillary Retinal Nerve Fibre Layer. AB - INTRODUCTION: We compared the thickness of the peripapillary retinal nerve fiber layer (RNFL) in patients with diabetic macular edema (DME) and/against the thickness in the normal population. METHODS: This cross-sectional study compared the RNFL thickness in patients with DME (DME group) using optical coherence tomography (OCT) to a comparable group of healthy (nondiabetic) patients (control group). Measurements were performed in different/the four peripapillary quadrants and in the macula region for the fovea, parafoveal, and perifoveal areas. The mean RNFL thickness was compared between both groups. RESULTS: There were fifty eyes of fifty nonglaucomatous diabetic patients with DME (29 with nonproliferative diabetic retinopathy [PDR] and 21 with PDR), and fifty eyes in the control group. The macular regions were significantly thicker in the DME group compared to the control group. The central foveal thickness was 149 MU thicker in eyes with DME compared to the control group (P < 0.001). The difference in total RNFL thickness between groups was not significant (4.4 MU [95% confidence interval: -3.1 to +12]). The between-group differences in peripapillary RNFL thickness by age group, glycemic control, history of intravitreal treatments, and refractive errors were not statistically significant (P > 0.05, all comparisons). CONCLUSION: Peripapillary RNFL thickness measurements were not significantly influenced by DME. Hence, OCT parameters could be used to monitor/early detect glaucomatous eyes even in the presence of DME. PMID- 27555708 TI - Argon Laser Photoablation for Treating Benign Pigmented Conjunctival Nevi. AB - PURPOSE: To evaluate the outcomes of argon laser photoablation of benign conjunctival pigmented nevi with different clinical presentations. PATIENTS AND METHODS: This interventional case series was conducted between July 2014 and January 2015. Patients presenting with benign conjunctival nevi were included. Data were collected on the clinical features at presentation, argon laser photoablation, and follow-up at 8 and 24 weeks. Postoperative photography allowed recording of the success of each case and the overall success rate. Complete removal of conjunctival pigments was considered an absolute success. Partial pigmentation requiring repeat laser treatment was considered a qualified success. RESULTS: There were 14 eyes (four right eyes and ten left eyes) with benign pigmented conjunctival nevi. There were three males and eight females in the study sample. The median age was 36 (25% percentile: 26 years). Three patients had bilateral lesions. The nevi were located temporally in nine eyes, nasally in three eyes, and on the inferior bulbar conjunctiva in two eyes. The mean horizontal and vertical diameters of nevi were 5 +/- 2 mm and 4 +/- 2.7 mm, respectively. The mean follow-up period was 5 months. Following laser treatment, no eyes had subconjunctival hemorrhage, infection, scarring, neovascularization, recurrence, or corneal damage. The absolute success rate of laser ablation was 79%. Three eyes with elevated nevi had one to three sessions of laser ablation resulting in a qualified success rate of 100%. CONCLUSIONS: Argon laser ablation was a safe and effective treatment for the treatment of selective benign pigmented conjunctival nevi in Arab patients. PMID- 27555709 TI - Ocular Pulse Amplitude and Retinal Vessel Caliber Changes after Intravitreal Dexamethasone Implant. AB - PURPOSE: The purpose of this study is to evaluate possible changes in ocular pulse amplitude (OPA), retinal arteriole caliber (RAC), and retinal venule caliber (RVC), following the intravitreal injection of dexamethasone implants (DIs). METHODS: Thirty-four eyes of 34 patients with macular edema were included. All participants received a full ophthalmologic examination at baseline. RAC and RVC were measured via optical coherence tomography; OPA and intraocular pressure (IOP) were measured via dynamic contour tonometry at baseline, month 1, and month 3. Statistical analysis was performed for before-after comparison of OPA, IOP, RAC, and RVC measurements. RESULTS: The mean OPA (in order to baseline, month 1, month 3) was 2.8 +/- 0.8, 2.9 +/- 1.0, 2.9 +/- 0.9. The mean IOP was 16.8 +/- 2.9, 17.3 +/- 2.7, 18.4 +/- 2.9 mmHg. The mean RAC was 97.8 +/- 9.2, 97.2 +/- 9.0, 97.6 +/- 9.4. The mean RVC was 124.4 +/- 8.2, 124.8 +/- 8.8, 123.8 +/- 8.2. There were no statistically significant changes in RAC (P = 0.688), RVC (P = 0.714), OPA (P = 0.348), and IOP (P = 0.115). There was also no correlation between RAC and OPA (r = 0.12, P = 0.62) or RVC and OPA (r = 0.16, P = 0.68) at the last visit. CONCLUSION: The intravitreal injection of DI does not significantly affect RAC, RVC, or OPA, which indicates that the treatment does not alter overall retinal-choroidal vasculature or hemodynamics. PMID- 27555710 TI - Bilateral Central Retinal Vein Occlusion as Presenting Feature of Chronic Myeloid Leukemia. AB - Central retinal vein occlusion (CRVO) is a common pathology of the retinal vasculature. Patients with CRVO usually present with a drop in visual acuity. The condition bears no specific therapy; treatment is aimed at the management of potentially blinding complications, of which there are many. With majority of cases being unilateral, bilateral CRVO is usually associated with an underlying systemic illness such as a hyperviscosity syndrome. Here, we present a case of a patient, who presented with a bilateral drop in vision diagnosed as bilateral CRVO on ophthalmic evaluation. Systemic workup revealed the presence of an underlying undiagnosed chronic myeloid leukemia. An initial presentation to the ophthalmologist is a rare occurrence in leukemic patients. This case report highlights the role of the ophthalmologist in diagnosing a potentially life threatening hematological illness. PMID- 27555711 TI - Multiple Ocular and Systemic Disorders in Association with Bilateral Duane's Retraction Syndrome. AB - Duane's retraction syndrome (DRS) is characterized by limitations in horizontal eye movements, globe retraction, and palpebral fissure narrowing on attempted adduction. This disorder is caused by a disturbance in innervation originating in the brain stem and represents <1% of all cases of strabismus. It is postulated that this syndrome is due to an insult during the early weeks (8-10 weeks) of pregnancy and is 10-20 times more frequently associated with other systemic congenital anomalies. This case report of bilateral DRS included bilateral iris retinal coloboma and congenital heart disease, sensory hearing loss, and inguinal hernia. PMID- 27555712 TI - Removal of Retained Descemets Membrane Using Femtosecond Laser. AB - We present a unique method of retrocorneal membrane removal with a femtosecond laser (FSL). A 22-year-old male who had undergone penetrating keratoplasty had a retained retrocorneal membrane and a double anterior chamber postoperatively. The membrane was dissected completely with the FSL and the free-floating membrane was removed. Histopathological evaluation confirmed the diagnosis of retained Descemets membrane (DM). There was improvement in uncorrected visual acuity from 20/300 to 20/50. Central corneal endothelial cell count was 810 cells/mm(2) preoperatively and 778 cells/mm(2) postoperatively. Inadvertent retention of DM may be safely treated with the FSL. Clarity and viability of the existing graft can be maintained. PMID- 27555713 TI - Bilateral Atypical Granular Corneal Dystrophy Associated with Unilateral Keratoconus in a Male Child. AB - A 14-year-old male presented with decreased vision. Slit lamp examination indicated multiple anterior corneal stromal opacities with clear intervening spaces accompanied with superficial subepithelial lines arranged in a quasi-whorl like fashion bilateral with greater prominence in the right eye. Corneal steepening associated with thinning was noted only in the right eye. Genetic analysis confirmed a mutation suggestive of granular corneal dystrophy. Here, we describe a rare case of an atypical granular dystrophy associated with unilateral keratoconus in a male child. PMID- 27555714 TI - Achieving Controlled Intraocular Pressure and Restoration of Vision Following Proactive Treatment of Total Choroidal Detachment Due to Endocyclophotocoagulation. AB - Ocular hypotony due to choroidal detachment (CD) following endocyclophotocoagulation (ECP) is transient. If hypotony lasts for more than 1 week, it could affect vision. This is a case of refractory glaucoma following cataract surgery that was managed by ECP. We drained subchoroidal fluid as CD did not resolve after 1 week. After 5 months, the intraocular pressure was restored to 16 mmHg with one topical glaucoma medication, uncorrected vision improved to 20/300, and with aphakic soft contact lens, it was 20/50. Ophthalmologists facing such complications need not panic and manage hypotony, and the prognosis of such intervention seems to be promising. PMID- 27555715 TI - A Surprise in the Lacrimal Sac. AB - To present a case with recurrent dacryocystitis as an unusual complication of medial orbital wall fracture repair with cartilage tissue graft. A 20-year-old male had facial trauma and underwent surgery to reconstruct right medial orbital wall fracture. During follow-up, he presented with continuous epiphora, mucopurulent discharge from the right eye. A thorough history taking indicated that medial orbital fracture was reconstructed with postauricular cartilage. We planned a standard external dacryocystorhinostomy (DCR). During the creation of lacrimal sac flaps, hard tissue was noted in the lacrimal sac. This tissue was excised and sent for pathological examination. The pathological examination revealed cartilage tissue. There were no further ipsilateral symptoms or complications after DCR. In patients with lacrimal system injury related to orbital wall fracture, iatrogenic foreign bodies in the lacrimal sac should be considered in patients with recurrent dacryocystitis who had reconstructive surgery for facial and orbital trauma. PMID- 27555716 TI - Traumatic Ghost Cell Glaucoma with Successful Resolution of Corneal Blood Staining Following Pars Plana Vitrectomy. AB - Ghost cell glaucoma (GCG) was first described in 1976. It is a type of a secondary open angle glaucoma, which occurs following long-standing vitreous hemorrhage. The ghost cells are rigid and less pliable than fresh red blood cells; therefore, they may cause direct obstruction of the trabecular meshwork and secondary increase in the intraocular pressure (IOP). This case report presents the diagnosis and management of a rare case of traumatic GCG after vitreous hemorrhage in a phakic child. Pars plana vitrectomy was done after unsuccessful medical therapy and the diagnosis was confirmed by cytopathology. Surprisingly, spontaneous resolution of the corneal blood staining occurred. The outcome in this case was favorable with controlled IOP in the affected eye. PMID- 27555717 TI - Corneal Epitheliopathy After Trauma by Fake Snow Powder in a 7-year-old Child. AB - Fake snow is a polymer of sodium polyacrylates used in games and celebrations. Despite the product leaflet that indicates safety, contact with the ocular surface can cause injury. We report a case of a child with corneal epitheliopathy due to a chemical burn injury after ocular surface contact with fake snow. The case was managed with epithelial debridement and a bandage contact lenses and topical antibiotics with complete resolution. PMID- 27555718 TI - Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane. AB - A 58-year-old female presented with intracameral retained perfluoro-n-octane (PFO) following previous retinal reattachment surgery. After 4 years of follow-up without related sequelae, the patient complained of a gradual decrease in vision secondary to corneal edema with whitish corneal precipitate inferiorly corresponding to the area of retained PFO. Three weeks after anterior chamber washout, corneal edema resolved and the patient obtained 20/40 visual acuity. Even though PFO considered to have a relatively good safety profile, early anterior chamber washout may prevent corneal toxicity and avoid later persistent corneal decompensation. PMID- 27555719 TI - Unilateral Glaucoma Associated with Conjunctival Angioma and Choroidal Thickening without Facial Angioma. AB - We report a case of a suspected Sturge-Weber syndrome variant diagnosed at the age of 58 with the help of enhanced depth imaging spectral-domain ocular coherence tomography (EDI-SDOCT). A 58-year-old female with unilateral glaucoma was suspected to have choroidal vascular lesion, conjunctival angioma, and no facial port-wine stain who presented to the clinic with bleb dysesthesia many years after trabeculectomy. EDI-SDOCT was performed and revealed markedly increased choroidal thickness in the affected eye. EDI-SDOCT may be helpful in diagnosing Sturge-Weber variants without facial involvement and may aid in the investigation of the pathogenesis of this disease. PMID- 27555720 TI - Death in dental clinic: Indian scenario. AB - Deaths during dental treatment or as a result of dental treatment are rare, but the unfortunate fact is that such deaths do occur. Unexpected death of a patient can be emotionally draining and even harrowing to his or her relatives. The death of a patient may bring an enormous feeling of anxiety both at the personal and professional level, stress, profound grief, damage to self-esteem, loss of self confidence, reputation, and specter of litigation on a dental surgeon. No dentist can be guaranteed to be free of such an incident during the course of his or her practice. The dentist should respond in a compassionate and respectful manner in case of such unfortunate tragic events, and also ensure self-protection. This article emphasizes on prevention of such incidents and throws some light on how to respond in case of an unfortunate death in a dental clinic, including the medico-legal aspects. PMID- 27555721 TI - Correlation of calcification of permanent mandibular canine, mandibular premolars, and permanent mandibular first and second molars with skeletal maturity in Indian population. AB - CONTEXT: Morphological variation in children can be understood by the knowledge of growth and development. The state of dental development can be used in forensic odontology to ascertain the age of an unidentified child. AIMS: This study aims to investigate the relationship of the stages of calcification of the permanent mandibular canine, mandibular premolars, and permanent mandibular first and second molars with skeletal maturity using panoramic and hand-wrist radiographs. SETTINGS AND DESIGN: This descriptive work was designed as a cross sectional study. MATERIALS AND METHODS: The study was conducted on 300 healthy subjects (150 males and 150 females) ranging 7-20 years of age. Demirjian's method and Bjork, Grave, and Brown's method were used to correlate teeth calcification and skeletal maturity, respectively. STATISTICAL ANALYSIS USED: Descriptive statistics and Spearman's rank correlation coefficient were used. RESULTS: 1. Correlation coefficients between the skeletal maturity stages and the developmental stages of the five teeth ranged 0.461-0.877 for females and 0.480 0.790 for males. 2. The second molar showed the highest and the first molar showed the lowest relationship for female and male subjects in the Indian population. CONCLUSIONS: The findings of this study indicate that tooth calcification stages might be clinically used as a maturity indicator of the pubertal growth period. PMID- 27555722 TI - Radiographic evaluation of mandibular ramus for gender estimation: Retrospective study. AB - BACKGROUND AND AIMS: Gender estimation is a very important part of a study in the field of anthropology and forensic sciences. In the skeleton, gender estimation is the first step of the identification process as subsequent methods for age and stature estimation are sex-dependent. Skeletal components such as the pelvis and skull are investigated for gender estimation and the mandible is a practical element to analyze sexual dimorphism in fragmented bones. The aim of the present study is to measure, compare, and evaluate various measurements of the mandibular ramus, observed in digital orthopantomographs and also to assess the usefulness of the mandibular ramus as an aid in gender estimation. MATERIALS AND METHODS: A radiographic retrospective study was conducted using 80 digital orthopantomographs to measure, compare, and evaluate the measurements of the mandibular ramus such as maximum ramus breadth, maximum ramus height, and coronoid heightusing Planmeca ProMax((r)) digital machine to assess the usefulness of mandibular measurements in gender estimation. RESULTS: Descriptive statistics of various measurements and associated univariate F ratios for both the sexes were determined. Four variables were significant predictor in classifying a given sample (P < 0.001). The F-statistic values indicated that measurements expressing the greatest sexual dimorphism were noticed in the maximum ramus height. CONCLUSION: Mandibular ramus can be considered as a valuable tool in gender estimation and the most reliable measurements were obtained of linear objects in the horizontal plane by digital panoramic imaging. PMID- 27555723 TI - Location of mental foramen using digital panoramic Radiography. AB - OBJECTIVE: Comparative evaluation of the location of mental foramen in different age groups. Determine the variation in position of mental foramen with gender using digital panoramic radiography. MATERIALS AND METHODS: Digital panoramic radiographs of 250 patients were reviewed. The study population was divided into five age groups with 50 patients each. Radiographic position of mental foramen was evaluated in each radiograph based on three parameters. Measurements were taken in each radiograph using Planmeca Dimaxis pro version 4.4.0 (Helsinki, Finland). The collected data were subjected to statistical analysis using paired Student's t-test. RESULTS: The mean distance of position of mental foramen showed a significant variation within the five age groups. In the first group, female patients showed an increase in mean distance of mental foramen position in relation to three parameters. From the second to fifth groups, male patient showed an increase in the mean distance of mental foramen position. The first and fifth group showed a reduced mean distance of mental foramen position when compared to other age groups. CONCLUSION: This study concluded that the position of mental foramen varies with age. There was a gender-related variation in position of mental foramen within the population too. PMID- 27555724 TI - Mandibular canine dimensions as an aid in gender estimation. AB - BACKGROUND: All humans have an identity in life; compassionate societies require this identity to be recognized even after death. OBJECTIVES: To measure the dimensions of the mandibular canine and assess the usefulness of the mandibular canine as an aid in gender estimation. MATERIALS AND METHODS: The study population comprised 200 subjects inclusive of 100 males and 100 females with an age range of 18-25 years. Measurements made in mm at the contact point were of mesiodistal width of the right and left canines and intercanine distance both intraorally and on casts, and the mandibular canine index (MCI) was calculated. The obtained data were subjected to t-test/Mann-Whitney test and discriminant function analysis. RESULTS: All parameters of mandibular canines, namely, intercanine distance, canine width, and canine index were greater in males compared to females suggesting significant sexual dimorphism of mandibular canines. On subjecting the data to discriminant function analysis, it classified sex correctly in 73% of the samples. CONCLUSION: The result of our study establishes the existence of significant sexual dimorphism in mandibular canines. We can therefore, recommend the use of mandibular canine dimensions as an applicable and additional method for gender determination in human identification. PMID- 27555725 TI - Analysis of dental hard tissues exposed to high temperatures for forensic applications: An in vitro study. AB - AIM: The aim of this study was to observe and record the macroscopic, radiographic, and microscopic findings obtained after subjecting the teeth to high temperatures. MATERIALS AND METHODS: An in vitro study was conducted to observe macroscopic, radiographic, and microscopic changes in dental hard tissues in 60 unrestored non carious extracted human teeth. The teeth were grouped based on age: Below 30 years, 30-40 years, and above 40 years The teeth from each age group were further divided into five subgroups, and each subgroup was subjected to a particular temperature: 200 degrees C, 400 degrees C, 600 degrees C, 800 degrees C, and 1000 degrees C. [C = Celsius]. RESULTS: Various degrees of changes in relation to temperature were observed macroscopically, radiographically, and microscopically. The histological examination was limited for teeth exposed to 200 degrees C. CONCLUSION: This investigation was carried out to study the gross changes, radiographic changes and histological changes in dental hard tissues exposed to high temperatures, which is an important part of forensic science. The aforementioned alterations caused by heat may provide useful information about temperature ranges and duration of exposure to high temperatures. PMID- 27555726 TI - Sex determination by mandibular ramus: A digital orthopantomographic study. AB - AIMS AND OBJECTIVES: (1) To determine the usefulness of mandibular ramus as an aid in sex determination. (2) To evaluate Anteroposterior | superioinferior angle of mandibular condyle. MATERIALS AND METHODS: A retrospective study was conducted using orthopantomographs of 60 males and 60 females, which were taken using Kodak 8000C Digital Panoramic and Cephalometric System (73 kVp, 12 mA, 13.9 s). The age group ranged between 18 - 45 years. Mandibular ramus measurements were carried out using Master View 3.0 software. The measurements of the mandibular ramus will be subjected to Discriminant function analysis. RESULTS: Maximum ramus breadth, Minimum ramus breadth, Condylar height, Projective height of ramus Coronoid height were calculated for both the sexes differently with the formula & analyzed with Discriminant function analysis using Fischer exact test. The P value was statistically significant with the P value < 0.05 for the following parameters Max. ramus breadth, Condylar height and Projective height of ramus. CONCLUSION: Mandibular ramus measurements can be a useful tool for gender determination. PMID- 27555727 TI - Mesiodistal odontometrics as a distinguishing trait: A comparative preliminary study. AB - INTRODUCTION: Sex determination is a vital step in reconstructing an individual profile from unidentified skeletal remnants. Variations in tooth size are influenced by genetic and environmental factors. Tooth size variations have been reported among different populations. AIM: To identify the sex by determining the mesiodistal (MD) dimensions of maxillary canines. OBJECTIVES: (1) To compare the MD diameter of all maxillary canines - (a) in the entire urban and tribal population, (b) in urban male and urban female populations, (c) in tribal male and tribal female populations, and (d) in the entire male and female populations and (2) To estimate the percentage of sexual dimorphism individually in urban and tribal populations. MATERIALS AND METHODS: Fifty subjects each from urban and tribal populations in equal gender ratio were selected in Khammam district, Telangana, for the purpose of this study. After obtaining informed consent, maxillary study models of the selected subjects were made. MD diameters of left and right maxillary canines were measured on casts using vernier calipers. The obtained data were subjected to statistical analysis. RESULTS: (1) The total tribal population showed a greater MD diameter of maxillary canines than the total urban population, (2) Urban males showed a greater MD diameter of maxillary canines than urban females, (3) Tribal males showed a greater MD diameter of maxillary canines than tribal females, (4) The entire male population showed a greater MD diameter of maxillary canines than the entire female population, and (5) The percentage of dimorphism between males and females in individual groups was found to be significant. CONCLUSION: The study showed maxillary canines exhibiting significant sexual dimorphism and can be used as a distinguishing trait for sex determination along with other procedures. PMID- 27555728 TI - Oral autopsy: A simple, faster procedure for total visualization of oral cavity. AB - Identification of humans, especially in mass disaster is a challenging aspect for team members of the disaster victim identification (DVI) unit. Identification is necessary for humanitarian and emotional reasons and for many legal issues, particularly for family members. In the modern day, all possible methods have been applied for establishing the identification of deceased individuals. The DVI team comprises specialists from different disciplines. The forensic dentist plays a major role in the identification of victims in disaster. To establish a simple, faster and time saving procedure for Postmortem dental identification in mass disaster. In this article, we present a simpler and faster method, which helps in gaining access into the oral cavity that helps in the recording of postmortem oral findings where required. PMID- 27555729 TI - Study on eunuchs/transgenders: An opinion. PMID- 27555730 TI - Histopathological evaluation of tissue undergoing thermal insult. AB - CONTEXT: Thermal insult is the major cause of thermal injury or death and in case of death due to thermal injury the body often has to be recovered from the site. Histologically, one can predict whether the victim was alive or dead when the fire was on going. However, determination of probable cause of thermal insult to which victim subjected to be difficult when the victim's body is found somewhere else from the crime scene or accident site or found alone. Hence, histopathological evaluation of the tissue which has undergone thermal insult in such conditions could help to place evidence in front of law officials, regarding probable condition, or scenario at time of burn of victim. AIMS: Keeping this as a criteria in this study we aim to evaluate burnt tissue histopathologically, that undergone various degree of thermal insult, which simulates various real life scenario for mortality in burn cases. SETTINGS AND DESIGN: We evaluate the changes in hematoxylin and eosin staining pattern of tissue which has undergone thermal insult compared to normal tissue and also the progressive changes in staining pattern, architectural, and cellular details. MATERIALS AND METHODS: Samples were taken from the patients, in various surgical procedures. Each sample was cut into five parts with close margins so that each burnt tissue is evaluated for same field or region. The tissue that obtained was immediately subjected to varying degree of temperature over a specific period so as to simulate the various real-life condition. Then the tissues were fixed, processed, and stained with routine H and E staining. The processed slides of tissue were examined under the microscope, and the staining, and architectural changes were evaluated and described. RESULTS: Results show that there was a progressive changes in the architectural pattern of the epithelium and connective tissue showing cleft formation and vacuolization, staining pattern also shows mixing of stains progressively as the severity of thermal insult increases. PMID- 27555731 TI - Validity of Carrea's index in stature estimation among two racial populations in India. AB - BACKGROUND: Stature is considered to be one of the "big fours" in forensic anthropology. Though Carrea's Index was published as early as 1920 it has not been validated in any other population apart from the Brazilians. AIM: The present study was conducted to validate Carrea's index in stature estimation in two different racial populations in India. MATERIALS AND METHODS: The study was carried out in a sample of 100 persons comprising of 25 Aryan males, 25 Aryan females, 25 Dravidian males, and 25 Dravidian females in the age group of 18-30 years. The maximum and minimum stature of all individuals was estimated by Carrea's Index. The actual stature was measured by an anthropometer. The estimated stature was compared with the actual stature and percentage of success was calculated. RESULTS: The Carrea's Index was found to be valid in predicting the stature of 80% Dravidian and 84% Aryan males, the difference being statistically insignificant (Fisher Exact test-0.16; P = 0.99). The stature of 76% of females in both Aryan and Dravidian races was successfully predicted by Carrea's index. Regression analysis showed that the minimum estimated height was more valid in estimating the stature of Aryan and Dravidian population. CONCLUSION: The validity to use Carrea's index in Aryan and Dravidian population was evaluated and found to be valid. PMID- 27555732 TI - Applicability of the Ricketts' posteroanterior cephalometry for sex determination using logistic regression analysis in Hispano American Peruvians. AB - BACKGROUND: The Ricketts' posteroanterior (PA) cephalometry seems to be the most widely used and it has not been tested by multivariate statistics for sex determination. OBJECTIVE: The objective was to determine the applicability of Ricketts' PA cephalometry for sex determination using the logistic regression analysis. MATERIALS AND METHODS: The logistic models were estimated at distinct age cutoffs (all ages, 11 years, 13 years, and 15 years) in a database from 1,296 Hispano American Peruvians between 5 years and 44 years of age. RESULTS: The logistic models were composed by six cephalometric measurements; the accuracy achieved by resubstitution varied between 60% and 70% and all the variables, with one exception, exhibited a direct relationship with the probability of being classified as male; the nasal width exhibited an indirect relationship. CONCLUSION: The maxillary and facial widths were present in all models and may represent a sexual dimorphism indicator. The accuracy found was lower than the literature and the Ricketts' PA cephalometry may not be adequate for sex determination. The indirect relationship of the nasal width in models with data from patients of 12 years of age or less may be a trait related to age or a characteristic in the studied population, which could be better studied and confirmed. PMID- 27555733 TI - Evaluation of skeletal maturation using mandibular third molar development in Indian adolescents. AB - OBJECTIVE: This study was done with the following objectives: to estimate dental maturity using the Demirjian Index (DI) for the mandibular third molar; to investigate the relationship between dental maturity and skeletal maturity among growing patients; to evaluate the use of the mandibular third molar as an adjunctive tool for adolescent growth assessment in combination with the cervical vertebrae; to evaluate the clinical value of the third molar as a growth evaluation index. MATERIALS AND METHODS: Samples were derived from panoramic radiographs and lateral cephalograms of 615 subjects (300 males and 315 females) of ages ranging 9-18 years, and estimates of dental maturity (DI) and skeletal maturity [cervical vertebrae maturation indicators (CVMI)] were made. RESULTS: A highly significant association (r = 0.81 for males and r = 0.72 for females) was found between DI and CVMI. DI Stage B corresponded to Stage 2 of CVMI (prepeak of pubertal growth spurt) in both sexes. In males, DI stages C and D represent the peak of the pubertal growth spurt. In females, stages B and C show that the peak of the pubertal growth spurt has not been passed. DI stage E in females and DI Stage F in males correlate that the peak of the pubertal growth spurt has been passed. CONCLUSION: A highly significant association exists between DI and CVMI. Mandibular third molar DI stages are reliable adjunctive indicators of skeletal maturity. PMID- 27555734 TI - Pulp/tooth ratio of mandibular first and second molars on panoramic radiographs: An aid for forensic age estimation. AB - OBJECTIVE: To determine and compare the accuracy of pulp/tooth ratio method in mandibular first and second molar teeth in forensic age estimation. MATERIALS AND METHODS: A total 300 panoramic radiographs of the Gujarati population (187 males and 113 females) were studied. The measurements of Pulp Chamber Height (PCH) and Crown Root Trunk Height (CRTH) were performed on the mandibular first and second molar teeth. The acquired data was subjected to correlation and regression. RESULTS: The pulp chamber crown root trunk height ratios (PCTHR) of both the first (r = -0.609) and second molars (r = -0.422) were significantly correlated with the age of the individual. Individual regression formulae were derived for both the teeth which were then used separately to calculate the age. The standard errors estimate (SEE) for the first and second molars were 8.84 years and 10.11 years, respectively. There was no statistically significant difference between chronological and calculated age by both the teeth (P = 1.000). CONCLUSION: The mandibular first and second molar is a potential tool for age estimation in forensic dentistry. The pulp/tooth ratio of both the teeth is a useful method for forensic age prediction with reasonable accuracy in the Gujarati population. PMID- 27555735 TI - Documentation of postmortem changes in salivary gland architecture and staining characteristics. AB - CONTEXT: Estimation of time passed since death continues to be a major problem for the forensic pathologist and its determination plays an important and vital role in medico-legal cases. The histological studies on various tissues after death have been mostly confined to single organ or tissue by individual workers at different atmospheric conditions. AIMS: The aim of this study is to determine the best rehydrating solution for dehydrated tissues in postmortem examination. SETTINGS AND DESIGN: This study was specific to salivary gland tissues and certain pattern of changes were determined during postmortem time intervals using hematoxylin and eosin stain and special stains like mucicarmine and alcian blue. MATERIALS AND METHODS: The study was divided into two groups. (1) Group A: Normal tissue samples (twenty normal salivary gland tissue samples left without fixation for varying periods of time). (2) Group B: Control group (twenty normal salivary gland tissue samples immediately fixed in formalin). The three different rehydrating agents used in this study were glycerol, normal saline and modified Ruffer solution. STATISTICAL ANALYSIS USED: Not required. RESULTS: Modified Ruffer solution is the best when compared to glycerol and normal saline for rehydration of dehydrated tissues. CONCLUSIONS: Thus in our study we conclude that the tissue which had been dehydrated at the crime scene for a fairly long period showed better rehydration with modified Ruffer solution and yield good cellular and nuclear details. PMID- 27555736 TI - A questionnaire survey on forensic odontology: Are we really aware? AB - INTRODUCTION: The role of a dentist is not only to examine and treat the oral diseases but also to assist the legal authorities by means of its branch-forensic odontology. Through forensic odontology, a dentist plays a very important role in crime investigation of any type. OBJECTIVE: To analyze the knowledge, awareness, and interest of forensic odontology among the dental teaching staff who are working in the dental colleges within the Delhi NCR. MATERIALS AND METHODS: A questionnaire of 12 questions (both open-ended and close-ended) was prepared and the survey was conducted with 200 dental teaching staff. RESULTS: A sufficient knowledge but poor awareness and interest among the dental teaching staff was observed. CONCLUSION: The study highlighted that although dental teaching staff themselves have sound knowledge regarding forensic odontology, their awareness and interest need to be upgraded on a regular basis. The success of acquiring such extensive knowledge would be valid if better job opportunities in these fields would be increased. PMID- 27555737 TI - Assessment of histological changes in antemortem gingival tissues fixed at various time intervals: A method of estimation of postmortem interval. AB - INTRODUCTION: Conventional methods to estimate the time of death are adequate, but a histological method is yet unavailable to assess postmortem interval (PMI). The autolytic changes that occur in an unfixed antemortem gingival tissue which reflects histologically at an early stage are similar to changes that occur in postmortem tissue. These histological changes can be used and applied in a postmortem tissue as a method to assess PMI. AIMS: The aim of the study is to assess the histological changes in a gingival tissue left unfixed for various time intervals and to correlate the findings with duration. MATERIALS AND METHODS: Sixty gingival tissues obtained from patients following therapeutic extractions, impactions, gingivectomy and crown lengthening procedures were used. Each tissue obtained was divided into two pieces and labeled as "A", the control group and " B" the study group. Tissues labeled "A" were fixed in 10% formalin immediately and tissues labeled"B" were placed in closed containers and fixed after 15, 30, 45 min, 1, 2, and 4 h time interval. Of the sixty tissues in the study group " B", ten tissues were used for each time interval under investigation. All the fixed tissues were processed, stained, assessed, and analyzed statistically using Pearson correlation and regression analysis. RESULTS: Histological changes appear at 15 min in an unfixed antemortem tissue. At 2 h interval, all layers with few cells in basal cell layer are involved. At 4 h interval, loss of stratification and complete homogenization of cells in the superficial layers with prominent changes in basal layer is evident. There was a positive correlation (<1.0) between the time interval and the appearance of the histological changes. CONCLUSION: Histological changes such as complete homogenization of cells in superficial layers and loss of epithelial architecture at 4 h in unfixed antemortem tissue may be used as a criterion to estimate PMI, after further studies on postmortem tissues. PMID- 27555738 TI - Age estimation based on Kvaal's technique using digital panoramic radiographs. AB - INTRODUCTION: Age estimation is important for administrative and ethical reasons and also because of legal consequences. Dental pulp undergoes regression in size with increasing age due to secondary dentin deposition and can be used as a parameter of age estimation even beyond 25 years of age. Kvaal et al. developed a method for chronological age estimation based on the pulp size using periapical dental radiographs. There is a need for testing this method of age estimation in the Indian population using simple tools like digital imaging on living individuals not requiring extraction of teeth. AIMS AND OBJECTIVES: Estimation of the chronological age of subjects by Kvaal's method using digital panoramic radiographs and also testing the validity of regression equations as given by Kvaal et al. MATERIALS AND METHODS: The study sample included a total of 152 subjects in the age group of 14-60 years. Measurements were performed on the standardized digital panoramic radiographs based on Kvaal's method. Different regression formulae were derived and the age was assessed. The assessed age was then correlated to the actual age of the patient using Student's t-test. RESULTS: No significant difference between the mean of the chronological age and the estimated age was observed. However, the values of the mean age estimated by using regression equations as given previously in the study of Kvaal et al. significantly underestimated the chronological age in the present study sample. CONCLUSION: The results of the study give an inference for the feasibility of this technique by calculation of regression equations on digital panoramic radiographs. However, it negates the applicability of same regression equations as given by Kvaal et al. on the study population. PMID- 27555739 TI - Analysis of RPE morphometry in human eyes. AB - PURPOSE: To describe the RPE morphometry of healthy human eyes regarding age and topographic location using modern computational methods with high accuracy and objectivity. We tested whether there were regional and age-related differences in RPE cell area and shape. METHODS: Human cadaver donor eyes of varying ages were dissected, and the RPE flatmounts were immunostained for F-actin with AF635 phalloidin, nuclei stained with propidium iodide, and imaged with confocal microscopy. Image analysis was performed using ImageJ (NIH) and CellProfiler software. Quantitative parameters, including cell density, cell area, polygonality of cells, number of neighboring cells, and measures of cell shape, were obtained from these analyses to characterize individual and groups of RPE cells. Measurements were taken from selected areas spanning the length of the temporal retina through the macula and the mid-periphery to the far periphery. RESULTS: Nineteen eyes from 14 Caucasian donors of varying ages ranging from 29 to 80 years were used. Along a horizontal nasal to temporal meridian, there were differences in several cell shape and size characteristics. Generally, the cell area and shape was relatively constant and regular except in the far periphery. In the outer third of the retina, the cell area and shape differed from the inner two-thirds statistically significantly. In the macula and the far periphery, an overall decreasing trend in RPE cell density, percent hexagonal cells, and form factor was observed with increasing age. We also found a trend toward increasing cell area and eccentricity with age in the macula and the far periphery. When individuals were divided into two age groups, <60 years and >=60 years, there was a higher cell density, lower cell area, lower eccentricity, and higher form factor in the younger group in the macula and the far periphery (p<0.05 for all measurements). No statistically significant differences in RPE morphometry between age groups were found in the mid-periphery. CONCLUSIONS: Human cadaver RPE cells differ mainly in area and shape in the outer one third compared to the inner two-thirds of the temporal retina. RPE cells become less dense and larger, lose their typical hexagonal shape, and become more oval with increasing age. PMID- 27555740 TI - Novel mutations in FZD4 and phenotype-genotype correlation in Chinese patients with familial exudative vitreoretinopathy. AB - PURPOSE: To identify novel mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) in southern China and to delineate the mutation-associated clinical manifestations. METHODS: Clinical data and genomic DNA were collected from 100 probands and their family members. The coding regions of FZD4 were screened for mutations with PCR and Sanger sequencing. Cosegregation analysis was used to verify suspected variants, and clinical symptoms in the probands were analyzed. RESULTS: Fourteen causative heterozygous mutations in FZD4 in 21 unrelated probands were noted, in 21.0% of the index patients (21/100). Four novel missense mutations (C45R, C45S, C53S, and C90R) and three novel deletion mutations (T326fsX356, G492fsX512, and S345_A351del) with a high possibility of pathogenicity were detected. None of these mutations were found in current online databases and 150 ethnically matched control subjects without retinopathy. The majority of the mutations in FZD4 were identified in probands with retinal folds (15/21) and ectopic macula (5/21). No mutations in FZD4 were found in probands with complete tractional retinal detachment in infancy or with mild asymptomatic FEVR in adulthood. CONCLUSIONS: Seven novel mutations found in this study have broadened the spectrum of mutations in FZD4 known to cause FEVR, providing a deeper understanding of this disease. The results show that mutations in FZD4 are associated with the phenotypes of retinal folds or ectopic macula in FEVR but might not be associated with extreme severe bilateral FEVR during infancy, at least in southern Chinese patients. PMID- 27555741 TI - A mathematical approach to human pterygium shape. AB - PURPOSE: Pterygium is a common lesion affecting the population in countries with high levels of ultraviolet exposure. The final shape of a pterygium is the result of a growth pattern, which remains poorly understood. This manuscript provides a mathematical analysis as a tool to determine the shape of human pterygia. MATERIALS AND METHODS: Eighteen patients, all affected by nasal unilateral pterygia, were randomly selected from our patient database independently of sex, origin, or race. We included all primary or recurrent pterygia with signs of proliferation, dry eye, and induction of astigmatism. Pseudopterygia were excluded from this study. Pterygia were outlined and analyzed mathematically using a Cartesian coordinate system with two axes (X, Y) and five accurate landmarks of the pterygium. RESULTS: In 13 patients (72%), the shape of the pterygia was hyperbolic and in five patients (28%), the shape was rather elliptical. CONCLUSION: This analysis gives a highly accurate mathematical description of the shape of human pterygia. This might help to better assess the clinical results and outcome of the great variety of therapeutic approaches concerning these lesions. PMID- 27555742 TI - Intraocular pressure dynamics with prostaglandin analogs: a clinical application of the water-drinking test. AB - AIM: To evaluate the clinical applicability of the water-drinking test in treatment-naive primary open-angle glaucoma patients. METHODS: Twenty newly diagnosed primary open-angle glaucoma patients and 20 healthy controls were enrolled in this prospective study. The water-drinking test was performed at baseline and 6 weeks and 3 months after prostaglandin analog treatment. Peak and fluctuation of intraocular pressure (IOP) measurements obtained with the water drinking test during follow-up were analyzed. Analysis of variance for repeated measures and paired and unpaired t-tests were used for statistical analysis. RESULTS: The mean baseline IOP values in patients with primary open-angle glaucoma were 25.1+/-4.6 mmHg before prostaglandin analog treatment, 19.8+/-3.7 mmHg at week 6, and 17.9+/-2.2 mmHg at month 3 after treatment. The difference in mean baseline IOP of the water-drinking tests was statistically significant (P<0.001). At 6 weeks of prostaglandin analog treatment, two patients had high peak and fluctuation of IOP measurements despite a reduction in baseline IOP. After modifying treatment, patients had lower peak and fluctuation of IOP values at month 3 of the study. CONCLUSION: Peak and fluctuation of IOP in response to the water-drinking test were lower with prostaglandin analogs compared with before medication. The water-drinking test can represent an additional benefit in the management of glaucoma patients, especially by detecting higher peak and fluctuation of IOP values despite a reduced mean IOP. Therefore, it could be helpful as a supplementary method in monitoring IOP in the clinical practice. PMID- 27555743 TI - Comparative evaluation of femtosecond laser-assisted cataract surgery and conventional phacoemulsification in white cataract. AB - PURPOSE: To compare femtosecond laser-assisted capsulotomy with conventional manual capsulorhexis in cases of white cataract. PATIENTS AND METHODS: The prospective comparative study enrolled 80 eyes (80 patients) with white cataract that underwent either femtosecond laser-assisted cataract surgery (Group I, n=40) or conventional manual phacoemulsification (Group II, n=40) at a tertiary care ophthalmic institution. The groups were divided based on the patient's choice and affordability of the procedure. Capsulotomy/capsulorhexis was evaluated in terms of size, circularity index (4Pi [area/perimeter2]), intraocular lens coverage, and continuity. Each group was further subdivided based on the release of white milky fluid on initiation of the capsulotomy/capsulorhexis, and the "fluid" cases were compared with the "no-fluid" cases. The primary outcome measure was capsulotomy/capsulorhexis characteristics in the two groups. The secondary outcome measures were intraoperative phacoemulsification parameters, intraoperative complications, and postoperative visual acuity. RESULTS: The size of the capsulotomy/capsulorhexis was 4.9+/-0.1 mm in Group I and 5.3+/-0.4 mm in Group II (P<0.001). Mean circularity index was 0.996+/-0.003 and 0.909+/-0.047 in Groups I and II, respectively (P<0.001). In Group I, free-floating circular capsulotomies were obtained in 52.5% (21/40) eyes; 37.5% (15/40) eyes had microadhesions; and 10% (4/40) eyes had incomplete capsulotomy in 1-2 clock hours. The incidence of residual adhesions was more in cases with release of white milky fluid (P=0.003). In Group II, a multistep capsulorhexis was performed in 70% (28/40) of the eyes. There was no difference in terms of visual outcomes and intraoperative complications. CONCLUSION: Femtosecond laser-assisted cataract surgery has the advantage of creating a circular and optimally sized capsulotomy in cases of white cataract. The release of white milky fluid during femtosecond laser delivery is the most important factor affecting the creation of a free floating capsulotomy. PMID- 27555744 TI - Advantages, limitations, and diagnostic accuracy of photoscreeners in early detection of amblyopia: a review. AB - Amblyopia detection is important to ensure proper visual development and avoid permanent decrease of visual acuity. This condition does not produce symptoms, so it is difficult to diagnose if a vision problem actually exists. However, because amblyopia treatment is limited by age, early diagnosis is of paramount relevance. Traditional vision screening (conducted in <3 years) is related with difficulty in getting cooperation from a subject to conduct the eye exam, so accurate objective methods to improve amblyopia detection are necessary. Handheld devices used for photoscreening or autorefraction could offer advantages to improve amblyopia screening because they reduce exploration time to just few seconds, no subject collaboration is needed, and they provide objective information. The purpose of this review is to summarize the main functions and clinical applicability of commercially available devices for early detection of amblyopia and to describe their differences, advantages, and limitations. Although the studies reviewed are heterogeneous (due to wide differences in referral criteria, use of different risk factors, different types of samples studied, etc), these devices provide objective measures in a quick and objective way with a simple outcome report: retest, pass, or refer. However, due to major limitations, these devices are not recommended, and their use in clinical practice is limited. PMID- 27555745 TI - The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye. AB - PURPOSE: To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. METHODS: The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). RESULTS: At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4+/-3.7 (baseline) to 17.3+/-9.1 (P<0.0001) and dry eye symptoms from 44.1+/-20.4 to 21.6+/-21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3+/-3.6 to 18.4+/-11.1 (P<0.0001) and dry eye symptoms from 49.1+/-21.0 to 24.0+/-23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). CONCLUSION: A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is associated with improved treatment outcomes. PMID- 27555746 TI - Effect of pupillary dilation on Haigis formula-calculated intraocular lens power measurement by using optical biometry. AB - PURPOSE: The purpose of this study was to evaluate the effect of pupillary dilation on the Haigis formula-calculated intraocular lens (IOL) power and ocular biometry measurements by using IOLMaster((r)). METHODS: A prospective study was performed for biometry measurements of 373 eyes of 192 healthy subjects using the IOLMaster at the outpatient department of King Chulalongkorn Memorial Hospital from February 2013 to July 2013. The axial length (AL), anterior chamber depth (ACD), keratometry (K), and IOL power were measured before and after 1% tropicamide eye drop instillation. The Haigis formula was used in the IOL power calculation with the predicted target to emmetropia. Each parameter was compared by a paired t-test prior to and after pupillary dilation. Bland-Altman plots were also used to determine the agreement between each parameter. RESULTS: The mean age of the subjects was 53.74+/-14.41 years (range 18-93 years). No differences in AL (P=0.03), steepest K (P=0.42), and flattest K (P=0.41) were obtained from the IOLMaster after pupillary dilation. However, ACD and IOL power were significantly different postdilation (P<0.01 and P<0.01, respectively). In ACD and IOL power measurements, the concordance rates were 93.03% and 97.05% within 95% limits of agreement (-0.48 to 0.26 mm and -1.09 to 0.88 D, respectively) in the Bland-Altman plots. CONCLUSION: Biometry measurements in the cycloplegic stage should be considered in the IOL formulas that use parameters other than AL and K. PMID- 27555747 TI - An upright eyedrop bottle: accuracy, usage of excess drops, and contamination compared to a conventional bottle. AB - PURPOSE: This study tested the feasibility of using an upright eyedrop bottle (UEB), a device designed to assist patients with eyedrop placement without reclining their head. PATIENTS AND METHODS: Experienced eyedrop users were enrolled who answered "yes" to the question, "Do you ever have trouble getting your eyedrops in?" After being shown a multimedia presentation and answering a questionnaire regarding eyedrop usage, participants were observed instilling eyedrops. Participants were instructed to instill a single eyedrop in each eye with both a standard bottle and the UEB. They repeated this process three times. With each trial, the amount of time taken to instill drops was recorded, as well as whether a drop landed in the eye (accuracy), if excess drops were used, and if the bottle tip was contaminated. RESULTS: Forty participants were enrolled, with an average age of 72.4+/-8.9 years; the majority were females (24 females). Thirty-four participants had been using eyedrops for at least 1 year. The time required to instill eyedrops was significantly less with the UEB in the second and third trials. There was no difference in accuracy between the conventional bottle and the UEB in the left or right eye in any trials. Significantly more participants used excess number of drops while using the conventional bottle in both the left and right eyes in all three trials. The bottle tip was never contaminated with the UEB. Depending on the trial and the eye, the conventional bottle was contaminated by between 42% and 53% of participants. CONCLUSION: The UEB has the potential to assist patients with eyedrop placement. Although there was no difference in accuracy between the UEB and the conventional bottle, the UEB was associated with less use of excess drops and less contamination of the bottle tip, compared to the conventional bottle. PMID- 27555748 TI - Etiologic analysis of 100 anatomically failed dacryocystorhinostomies. AB - BACKGROUND: The aim of this study was to assess the etiological factors contributing to the failure of a dacryocystorhinostomy (DCR). PATIENTS AND METHODS: Retrospective review was performed in 100 consecutive patients who were diagnosed with anatomically failed DCR at presentation to a tertiary care hospital over a 5-year period from 2010 to 2015. Patient records were reviewed for demographic data, type of past surgery, preoperative endoscopic findings, previous use of adjuvants such as intubation and mitomycin C, and intraoperative notes during the re-revision. The potential etiological factors for failure were noted. RESULTS: Of the 100 patients with failed DCRs, the primary surgery was an external DCR in 73 and endoscopic DCR in 27 patients. Six patients in each group had multiple revisions. The mean ages at presentation in the external and endoscopic groups were 39.41 years and 37.19 years, respectively. All patients presented with epiphora. The most common causes of failure were inadequate osteotomy (69.8% in the external group and 85.1% in the endoscopic group, P=0.19) followed by inadequate or inappropriate sac marsupialization (60.2% in the external group and 77.7% in the endoscopic group, P=0.16) and cicatricial closure of the ostium (50.6% in the external group and 55.5% in the endoscopic group, P=0.83). The least common causes such as ostium granulomas and paradoxical middle turbinate (1.37%, n=1) were noted in the external group only. CONCLUSION: Inadequate osteotomy, incomplete sac marsupialization, and cicatricial closure of the ostium were the most common causes of failure and did not significantly differ in the external and endoscopic groups. Meticulous evaluation to identify causative factors for failure and addressing them are crucial for subsequent successful outcomes. PMID- 27555749 TI - Visualization of a hyaluronan network on the surface of silicone-hydrogel materials. AB - Biotrue multipurpose solution (MPS) is a bioinspired disinfecting and conditioning solution that includes hyaluronic acid (HA) as a natural wetting agent. Previous studies demonstrated that HA sorbed from Biotrue MPS on both conventional and silicone hydrogel (SiHy) contact lens materials; an in vitro simulated-wear test validated the presence of HA on the lens surfaces for as long as 20 hours. In this study, the morphology and distribution of HA sorbed from both Biotrue and pure HA solution on SiHy contact lens surfaces was examined. Atomic force microscopy imaging was used to illustrate the topography of fresh SiHy contact lens materials before and after incubation with 0.1% (w/v) HA solution. The distribution, as well as fine details of the HA network, were resolved by first staining HA with Gram's safranin, then imaging with confocal laser-scanning microscopy and differential interference-contrast microscopy. In this approach, SiHy materials take up the dye (safranin) nonspecifically, such that the resultant safranin-HA complex appears dim against the fluorescent lens background. Balafilcon A was chosen as the representative of glassy SiHy lenses that require postpolymerization plasma treatment to increase wettability. Senofilcon A and samfilcon A were chosen as representatives of SiHy materials fabricated with an internal wetting agent. A confluent and dim HA-safranin network was observed adhered to balafilcon A, senofilcon A, and samfilcon A lens surfaces incubated with either 0.1% (w/v) HA solution or Biotrue MPS. Therefore, the conditioning function provided by Biotrue MPS may be in part explained by the presence of the HA humectant layer that readily sorbs on the various types of SiHy contact lens materials. PMID- 27555750 TI - Flurbiprofen-antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling. AB - Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug. PMID- 27555751 TI - Patients' empowerment, physicians' perceptions, and achievement of therapeutic goals in patients with type 1 and type 2 diabetes mellitus in Mexico. AB - BACKGROUND: Physicians' perception may not parallel objective measures of therapeutic targets in patients with diabetes. This is an issue rarely addressed in the medical literature. We aimed to analyze physicians' perception and characteristics of adequate control of patients with diabetes. PATIENTS AND METHODS: We studied information on physicians and their patients who participated in the third wave of the International Diabetes Management Practices Study registry in Mexico. This analysis was performed on 2,642 patients, 203 with type 1 diabetes mellitus (T1DM) and 2,439 with type 2 diabetes mellitus (T2DM), treated by 200 physicians. RESULTS: The patients perceived at target had lower hemoglobin A1c (HbA1c) and fasting blood glucose than those considered not at target. However, overestimation of the frequency of patients with HbA1c <7% was 41.5% in patients with T1DM and 31.7% in patients with T2DM (underestimation: 2.8% and 8.0%, respectively). The agreement between the physicians' perception and the class of HbA1c was suboptimal (kappa: 0.612). Diabetologists and endocrinologists tested HbA1c more frequently than primary care practitioners, internists, or cardiologists; however, no differences were observed in mean HbA1c, for both T1DM (8.4% vs 7.2%, P=0.42) and T2DM (8.03% vs 8.01%, P=0.87) patients. Nevertheless, insulin users perceived at target, who practiced self monitoring and self-adjustment of insulin, had a lower mean HbA1c than patients without these characteristics (mean HbA1c in T1DM: 6.8% vs 9.6%, respectively; mean HbA1c in T2DM: 7.0% vs 10.1%, respectively). CONCLUSION: Although there is a significant physicians' overestimation about the optimal glycemic control, this global impression and characteristics of patients' empowerment, such as self monitoring and self-adjustment of insulin, are associated with the achievement of targets. PMID- 27555752 TI - Modeling the hospital safety partnership preferences of patients and their families: a discrete choice conjoint experiment. AB - BACKGROUND: Patients and their families play an important role in efforts to improve health service safety. OBJECTIVE: The objective of this study is to understand the safety partnership preferences of patients and their families. METHOD: We used a discrete choice conjoint experiment to model the safety partnership preferences of 1,084 patients or those such as parents acting on their behalf. Participants made choices between hypothetical safety partnerships composed by experimentally varying 15 four-level partnership design attributes. RESULTS: Participants preferred an approach to safety based on partnerships between patients and staff rather than a model delegating responsibility for safety to hospital staff. They valued the opportunity to participate in point of service safety partnerships, such as identity and medication double checks, that might afford an immediate risk reduction. Latent class analysis yielded two segments. Actively engaged participants (73.3%) comprised outpatients with higher education, who anticipated more benefits to safety partnerships, were more confident in their ability to contribute, and were more intent on participating. They were more likely to prefer a personal engagement strategy, valued scientific evidence, preferred a more active approach to safety education, and advocated disclosure of errors. The passively engaged segment (26.7%) anticipated fewer benefits, were less confident in their ability to contribute, and were less intent on participating. They were more likely to prefer an engagement strategy based on signage. They preferred that staff explain why they thought patients should help make care safer and decide whether errors were disclosed. Inpatients, those with immigrant backgrounds, and those with less education were more likely to be in this segment. CONCLUSION: Health services need to communicate information regarding risks, ask about partnership preferences, create opportunities respecting individual differences, and ensure a positive response when patients raise safety concerns. PMID- 27555753 TI - First-ever ischemic stroke in elderly patients: predictors of functional outcome following carotid artery stenting. AB - Age is an important risk factor for stroke, and carotid artery stenosis is the primary cause of first-ever ischemic stroke. Timely intervention with stenting procedures can effectively prevent secondary stroke; however, the impact of stenting on various periprocedural physical functionalities has never been thoroughly investigated. The primary aim of this study was to investigate whether prestenting characteristics were associated with long-term functional outcomes in patients presenting with first-ever ischemic stroke. The secondary aim was to investigate whether patient age was an important factor in outcomes following stenting, measured by the modified Rankin scale (mRS). In total, 144 consecutive patients with first-ever ischemic stroke who underwent carotid artery stenting from January 2010 to November 2014 were included. Clinical data were obtained by review of medical records. The Barthel index (BI) and mRS were used to assess disability before stenting and at 12-month follow-up. In total, 72/144 patients showed improvement (mRS[+]), 71 showed stationary and one showed deterioration in condition (mRS[-]). The prestenting parameters, ratio of cerebral blood volume (1.41 vs 1.2 for mRS[-] vs mRS[+]), BI (75 vs 85), and high-sensitivity C reactive protein (hsCRP 5.0 vs 3.99), differed significantly between the two outcome groups (P<0.05). The internal carotid artery/common carotid artery ratio (P=0.011), BI (P=0.019), ipsilateral internal carotid artery resistance index (P=0.003), and HbA1c (P=0.039) were all factors significantly associated with patient age group. There was no significant association between age and poststenting outcome measured by mRS with 57% of patients in the >=75 years age group showing mRS(-) and 43% showing mRS(+) (P=0.371). Our findings indicate that in our elderly patient series, carotid artery stenting may benefit a significant proportion of carotid stenotic patients regardless of age. Ratio of cerebral blood volume, BI, and admission hsCRP could serve as important predictors of mRS improvement and may facilitate differentiation of patients at baseline. PMID- 27555754 TI - Surveying the effects of an exercise program on the sleep quality of elderly males. AB - BACKGROUND: Old age is a stage of life featured with many physiological and mental changes. The Iranian population is aging, and one of the problems that the elderly are faced with is sleep disorders. The present study is an attempt to examine the effectiveness of an exercise program on the sleep quality of the elderly. METHODS: A semi-experimental study was carried out on the elderly males referred to the Shahid Yari Elderly Center, Kermanshah, Iran. The sample group comprised of 46 participants: 23 in the experimental group and 23 in the control group. The study was carried out for a period of 2 months and follow-up was conducted every week. To improve the quality of sleep of the participants, a four stage exercise program was implemented and the collected data were analyzed by SPSS version 20. RESULTS: The results of a Mann-Whitney test showed that the quality of sleep of the majority in the experimental group improved compared with that of the control group (P<0.05). In addition, a Wilcoxon test showed improvement of the Petersburg's sleep quality index based on subelements and the results of a total score of sleep in the experimental group after the intervention. CONCLUSION: The study showed effectiveness of scheduled exercising on the quality of sleep of the elderly. It is recommended, therefore, to add an exercise program to the daily program of the elderly. PMID- 27555755 TI - Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment. AB - Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apoptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. PMID- 27555756 TI - Cause-specific mortality in individuals with severe alpha 1-antitrypsin deficiency in comparison with the general population in Sweden. AB - BACKGROUND: Severe alpha 1-antitrypsin deficiency (PiZZ) predisposes to morbidity and mortality due to early-onset emphysema and liver disease. The risk of death from other causes, including cardiovascular disease and cancer, has not been well investigated. We aimed to analyze cause-specific mortality in PiZZ individuals compared with the general Swedish population. METHODS: Data on 1,561 PiZZ individuals from the Swedish National AAT Deficiency Register, prospectively followed from 1991 to 2014, were analyzed. Causes of death according to the Swedish National Causes of Death Register for the study group were compared with those for the general Swedish population matched for age, sex, and calendar year, with the excess mortality expressed as standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). RESULTS: There were 524 deaths during the follow up period. PiZZ individuals had excess all-cause mortality compared with the Swedish general population (SMR 3.6, 95% CI 3.3-3.9). SMR for ischemic heart disease (IHD) was 0.5 (95% CI 0.3-0.8) and was similar for never and ever smokers, and in males and females. SMR for lung cancer was 0.9 (95% CI 0.4-1.7). PiZZ individuals had increased mortality compared with the general population for the following diseases: respiratory disease, SMR 48.4 (95% CI 43.0-54.5); primary liver carcinoma, SMR 90.0 (95% CI 59.3-130.9); complicated colon diverticulitis, SMR 20.8 (95% CI 6.7-48.6); and pulmonary embolism, SMR 6.9 (95% CI 3.3-12.7). CONCLUSION: PiZZ individuals had a reduced mortality risk of IHD. Mortality due to respiratory, hepatic disease, diverticulitis, and pulmonary embolism was markedly increased compared with the age- and sex-matched Swedish population. PMID- 27555757 TI - Respiratory muscle strength effect on linear and nonlinear heart rate variability parameters in COPD patients. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is recognized as a multisystemic inflammatory disease associated with extrapulmonary comorbidities, including respiratory muscle weakness and cardiovascular and cardiac autonomic regulation disorders. We investigated whether alterations in respiratory muscle strength (RMS) would affect cardiac autonomic modulation in COPD patients. METHODS: This study was a cross-sectional study done in ten COPD patients affected by moderate to very severe disease. The heart rate variability (HRV) signal was recorded using a Polar cardiofrequencimeter at rest in the sitting position (10 minutes) and during a respiratory sinus arrhythmia maneuver (RSA-M; 4 minutes). Linear analysis in the time and frequency domains and nonlinear analysis were performed on the recorded signals. RMS was assessed using a digital manometer, which provided the maximum inspiratory pressure (PImax) and the maximum expiratory pressure (PEmax). RESULTS: During the RSA-M, patients presented an HRV power increase in the low-frequency band (LFnu) (46.9+/-23.7 vs 75.8+/-27.2; P=0.01) and a decrease in the high-frequency band (HFnu) (52.8+/ 23.5 vs 24.0+/-27.0; P=0.01) when compared to the resting condition. Significant associations were found between RMS and HRV spectral indices: PImax and LFnu (r= 0.74; P=0.01); PImax and HFnu (r=0.74; P=0.01); PEmax and LFnu (r=-0.66; P=0.01); PEmax and HFnu (r=0.66; P=0.03); between PEmax and sample entropy (r=0.83; P<0.01) and between PEmax and approximate entropy (r=0.74; P=0.01). Using a linear regression model, we found that PImax explained 44% of LFnu behavior during the RSA-M. CONCLUSION: COPD patients with impaired RMS presented altered cardiac autonomic control, characterized by marked sympathetic modulation and a reduced parasympathetic response; reduced HRV complexity was observed during the RSA-M. PMID- 27555758 TI - Quality of life and adherence to inhaled corticosteroids and tiotropium in COPD are related. AB - BACKGROUND: Poor adherence to inhaled medications in COPD patients seems to be associated with an increased risk of death and hospitalization. Knowing the determinants of nonadherence to inhaled medications is important for creating interventions to improve adherence. OBJECTIVES: To identify disease-specific and health-related quality of life (HRQoL) factors, associated with adherence to inhaled corticosteroids (ICS) and tiotropium in COPD patients. METHODS: Adherence of 795 patients was recorded over 3 years and was deemed optimal at >75%-<=125%, suboptimal at >=50%-<75%, and poor at <50% (underuse) or >125% (overuse). Health related quality of life was measured with the Clinical COPD Questionnaire and the EuroQol-5D questionnaire. RESULTS: Patients with a higher forced expiratory volume in 1 second (FEV1)/vital capacity (VC) (odds ratio [OR] =1.03) and >=1 hospitalizations in the year prior to inclusion in this study (OR =2.67) had an increased risk of suboptimal adherence to ICS instead of optimal adherence. An increased risk of underuse was predicted by a higher FEV1/VC (OR =1.05). Predictors for the risk of overuse were a lower FEV1 (OR =0.49), higher scores on Clinical COPD Questionnaire-question 3 (anxiety for dyspnea) (OR =1.26), and current smoking (OR =1.73). Regarding tiotropium, predictors for suboptimal use were a higher FEV1/VC (OR =1.03) and the inability to perform usual activities as asked by the EuroQol-5D questionnaire (OR =3.09). A higher FEV1/VC also was a predictor for the risk of underuse compared to optimal adherence (OR =1.03). The risk of overuse increased again with higher scores on Clinical COPD Questionnaire question 3 (OR =1.46). CONCLUSION: Several disease-specific and quality of life factors are related to ICS and tiotropium adherence, but a clear profile of a nonadherent patient cannot yet be outlined. Overusers of ICS and tiotropium experience more anxiety. PMID- 27555759 TI - Impact of lung function on exacerbations, health care utilization, and costs among patients with COPD. AB - OBJECTIVE: To evaluate the impact of lung function, measured as forced expiratory volume in 1 second (FEV1) % predicted, on health care resource utilization and costs among patients with COPD in a real-world US managed-care population. METHODS: This observational retrospective cohort study utilized administrative claim data augmented with medical record data. The study population consisted of patients with one or more medical claims for pre- and postbronchodilator spirometry during the intake period (July 1, 2012 to June 30, 2013). The index date was the date of the earliest medical claim for pre- and postbronchodilator spirometry. Spirometry results were abstracted from patients' medical records. Patients were divided into two groups (low FEV1% predicted [,50%] and high FEV1% predicted [>=50%]) based on the 2014 Global Initiative for Chronic Obstructive Lung Disease report. Health care resource utilization and costs were based on the prevalence and number of discrete encounters during the 12-month postindex follow up period. Costs were adjusted to 2014 US dollars. RESULTS: A total of 754 patients were included (n=297 low FEV1% predicted group, n=457 high FEV1% predicted group). COPD exacerbations were more prevalent in the low FEV1% predicted group compared with the high group during the 12-month pre- (52.5% vs 39.6%) and postindex periods (49.8% vs 36.8%). Mean (standard deviation) follow up all-cause and COPD-related costs were $27,380 ($38,199) and $15,873 ($29,609) for patients in the low FEV1% predicted group, and $22,075 ($28,108) and $10,174 ($18,521) for patients in the high group. In the multivariable analyses, patients in the low FEV1% predicted group were more likely to have COPD exacerbations and tended to have higher COPD-related costs when compared with patients in the high group. CONCLUSION: Real-world data demonstrate that patients with COPD who have low FEV1% predicted levels use more COPD medications, have more COPD exacerbations, and incur higher COPD-related health care costs than those with high FEV1% predicted levels. PMID- 27555760 TI - Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice. AB - COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-alpha (TNF-alpha) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-alpha transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-alpha transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema. PMID- 27555761 TI - Alteration of spontaneous brain activity in COPD patients. AB - BACKGROUND AND OBJECTIVE: Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. PATIENTS AND METHODS: Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. RESULTS: Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. CONCLUSION: We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID- 27555762 TI - The inhibitory mechanism of Cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells. AB - OBJECTIVES: Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE) induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence. METHODS: Human bronchial epithelial cells (16HBE cells) cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS), PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway. RESULTS: Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence. CONCLUSION: CSE can induce cellular senescence in human bronchial epithelial cells, and ROS/PI3K/AKT/mTOR signaling pathway may play an important role in this process. C. sinensis can inhibit the CSE-induced senescence. PMID- 27555763 TI - Nrf2 expression is increased in peripheral blood mononuclear cells derived from mild-moderate ex-smoker COPD patients with persistent oxidative stress. AB - Inadequacy of antioxidant nuclear factor-E2-related factor 2 (Nrf2) and endoplasmic reticulum stress-mediated unfolded protein response has been implicated in severe chronic obstructive pulmonary disease (COPD) and cigarette smoking-induced emphysema. As evidence suggests that the ability to upregulate Nrf2 expression may influence the progression of COPD and no data exist up to now in ex-smokers with mild-moderate COPD, this study was first aimed to evaluate Nrf2 and unfolded protein response expression in peripheral blood mononuclear cells (PBMC) of mild-moderate ex-smokers with COPD compared to smoking habit matched non-COPD subjects. Then, we tested whether oxidative stress persists after cigarette smoking cessation and whether the concentrations of oxidized phospholipids (oxidation products of the phospholipid 1-palmitoyl-2-arachidonyl sn-glycero-3-phosphorylcholine [oxPAPC]) in the PBMC of the same subjects may have a causative role in determining the upregulation of Nrf2. The expression (mRNA and protein) of Nrf2 and of its related gene heme oxygenase-1 was significantly increased in COPD group without differences in the unfolded protein response. Plasma malondialdehyde, the circulating marker of oxidative stress, and oxPAPC in PBMC were significantly higher in COPD than in non-COPD subjects. The fact that the expression of p47phox, a subunit of NADPH oxidase, was increased in PBMC of COPD patients and that it was directly correlated with oxPAPC may indicate that oxPAPC may be one of the determinants of oxidative stress-induced Nrf2 upregulation. Finally, we also demonstrated that lung function inversely correlated with plasma malondialdehyde and with Nrf2 and heme oxygenase-1 mRNA expression in all subjects. Our results indicate that mild-moderate ex-smokers with COPD may be able to counteract oxidative stress by increasing the expression of Nrf2/antioxidant-response elements. Because Nrf2 failure significantly contributes to the development of COPD, our findings suggest that the possibility to prevent Nrf2 reduction may open a new scenario in helping to prevent the oxidative stress-associated lung function decline. PMID- 27555764 TI - Gallic acid conjugated with gold nanoparticles: antibacterial activity and mechanism of action on foodborne pathogens. AB - Foodborne pathogens, including Plesiomonas shigelloides and Shigella flexneri B, are the major cause of diarrheal endemics worldwide. Antibiotic drug resistance is increasing. Therefore, bioactive compounds with antibacterial activity, such as gallic acid (GA), are needed. Gold nanoparticles (AuNPs) are used as drug delivery agents. This study aimed to conjugate and characterize AuNP-GA and to evaluate the antibacterial activity. AuNP was conjugated with GA, and the core shell structures were characterized by small-angle X-ray scattering and transmission electron microscopy. Antibacterial activity of AuNP-GA against P. shigelloides and S. flexneri B was evaluated by well diffusion method. AuNP-GA bactericidal mechanism was elucidated by Fourier transform infrared microspectroscopic analysis. The results of small-angle X-ray scattering showed that AuNP-GA conjugation was successful. Antibacterial activity of GA against both bacteria was improved by conjugation with AuNP because the minimum inhibitory concentration value of AuNP-GA was significantly decreased (P<0.0001) compared to that of GA. Fourier transform infrared analysis revealed that AuNP-GA resulted in alterations of lipids, proteins, and nucleic acids at the bacterial cell membrane. Our findings show that AuNP-GA has potential for further application in biomedical sciences. PMID- 27555765 TI - Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique. AB - This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis - bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA phosphatidylcholine flavonosome, which revealed an average diameter of 375.93+/ 33.61 nm, with a zeta potential of -39.07+/-3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%+/-0.17%, 34.51%+/-2.07%, and 31.79%+/-0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 ug/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate. PMID- 27555766 TI - Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration. AB - In this study, bioactive scaffold of nano magnesium phosphate (nMP)/wheat protein (WP) composite (MWC) was fabricated. The results revealed that the MWC scaffolds had interconnected not only macropores (sized 400-600 MUm) but also micropores (sized 10-20 MUm) on the walls of macropores. The MWC scaffolds containing 40 w% nMP had an appropriate degradability in phosphate-buffered saline and produced a weak alkaline microenvironment. In cell culture experiments, the results revealed that the MWC scaffolds significantly promoted the MC3T3-E1 cell proliferation, differentiation, and growth into the scaffolds. The results of synchrotron radiation microcomputed tomography and analysis of the histological sections of the in vivo implantation revealed that the MWC scaffolds evidently improved the new bone formation and bone defects repair as compared with WP scaffolds. Moreover, it was found that newly formed bone tissue continued to increase with the gradual reduction of materials residual in the MWC scaffolds. Furthermore, the immunohistochemical analysis further offered the evidence of the stimulatory effects of MWC scaffolds on osteogenic-related cell differentiation and new bone regeneration. The results indicated that MWC scaffolds with good biocompability and degradability could promote osteogenesis in vivo, which would have potential for bone tissue repair. PMID- 27555767 TI - Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer. AB - Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs) were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween). A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%), and superior blood biocompatibility based on in vitro hemolysis assay. Blood circulation, tumor uptake, and antitumor activity of Cbz-NPs were assessed in prostatic cancer xenograft-bearing nude mice. Cbz-NPs exhibited prolonged blood circulation and greater accumulation of Cbz in tumors along with reduced toxicity compared to Cbz Tween. Moreover, hematoxylin and eosin histopathological staining of organs revealed consistent results. The levels of blood urea nitrogen and serum creatinine in drug-treated mice showed that Cbz-NPs were less toxic than Cbz Tween to the kidneys. In conclusion, Cbz-NPs provide a promising therapeutic for prostate cancer. PMID- 27555768 TI - Photothermal effects of laser-activated surface plasmonic gold nanoparticles on the apoptosis and osteogenesis of osteoblast-like cells. AB - The specific properties of gold nanoparticles (AuNPs) make them a novel class of photothermal agents that can induce cancer cell damage and even death through the conversion of optical energy to thermal energy. Most relevant studies have focused on increasing the precision of cell targeting, improving the efficacy of energy transfer, and exploring additional functions. Nevertheless, most cells can uptake nanosized particles through nonspecific endocytosis; therefore, before hyperthermia via AuNPs can be applied for clinical use, it is important to understand the adverse optical-thermal effects of AuNPs on nontargeted cells. However, few studies have investigated the thermal effects induced by pulsed laser-activated AuNPs on nearby healthy cells due to nonspecific treatment. The aim of this study is to evaluate the photothermal effects induced by AuNPs plus a pulsed laser on MG63, an osteoblast-like cell line, specifically examining the effects on cell morphology, viability, death program, and differentiation. The cells were treated with media containing 50 nm AuNPs at a concentration of 5 ppm for 1 hour. Cultured cells were then exposed to irradiation at 60 mW/cm(2) and 80 mW/cm(2) by a Nd:YAG laser (532 nm wavelength). We observed that the cytoskeletons of MG63 cells treated with bare AuNPs followed by pulsed laser irradiation were damaged, and these cells had few bubbles on the cell membrane compared with those that were not treated (control) or were treated with AuNPs or the laser alone. There were no significant differences between the AuNPs plus laser treatment group and the other groups in terms of cell viability, death program analysis results, or alkaline phosphatase and calcium accumulation during culture for up to 21 days. However, the calcium deposit areas in the cells treated with AuNPs plus laser were larger than those in other groups during the early culture period. PMID- 27555769 TI - Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy. AB - Gold nanoclusters (Au NCs) have exhibited great advantages in medical diagnostics and therapies due to their efficient renal clearance and high tumor uptake. The in vivo effects of the surface chemistry of Au NCs are important for the development of both nanobiological interfaces and potential clinical contrast reagents, but these properties are yet to be fully investigated. In this study, we prepared glutathione-protected Au NCs of a similar hydrodynamic size but with three different surface charges: positive, negative, and neutral. Their in vivo biodistribution, excretion, and toxicity were investigated over a 90-day period, and tumor uptake and potential application to radiation therapy were also evaluated. The results showed that the surface charge greatly influenced pharmacokinetics, particularly renal excretion and accumulation in kidney, liver, spleen, and testis. Negatively charged Au NCs displayed lower excretion and increased tumor uptake, indicating a potential for NC-based therapeutics, whereas positively charged clusters caused transient side effects on the peripheral blood system. PMID- 27555770 TI - A nano-sandwich construct built with graphene nanosheets and carbon nanotubes enhances mechanical properties of hydroxyapatite-polyetheretherketone scaffolds. AB - A nano-sandwich construct was built by combining two-dimensional graphene nanosheets (GNSs) and one-dimensional carbon nanotubes (CNTs) to improve the mechanical properties of hydroxyapatite-polyetheretherketone (HAP-PEEK) scaffolds for bone tissue engineering. In this nano-sandwich construct, the long tubular CNTs penetrated the interlayers of graphene and prevented their aggregation, increasing the effective contact area between the construct and matrix. The combination of GNSs and CNTs in a weight ratio of 2:8 facilitated the dispersion of each other and provided a synergetic effect in enhancing the mechanical properties. The compressive strength and modulus of the scaffolds were increased by 63.58% and 56.54% at this time compared with those of HAP-PEEK scaffolds, respectively. The carbon-based fillers, pulling out and bridging, were also clearly observed in the matrix. Moreover, the dangling of CNTs and their entangling with GNSs further reinforced the mechanical properties. Furthermore, apatite layer formed on the scaffold surface after immersing in simulated body fluid, and the cells attached and spread well on the surface of the scaffolds and displayed good viability, proliferation, and differentiation. These evidence indicate that the HAP-PEEK scaffolds enhanced by GNSs and CNTs are a promising alternative for bone tissue engineering. PMID- 27555771 TI - Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells. AB - Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-alpha (TNF- alpha) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter <200 nm and highly negative zeta potential (about -30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-alpha in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 uM) and major histocompatibility complex-class II molecule human leukocyte antigen - antigen D related (10 uM), both upregulated in response to TNF-alpha stimulation. Rsv-NLC were compared with free rsv; at 5 uM, rsv-NLC were able to inhibit nuclear factor kappa beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF alpha, while 10 uM free rsv were needed to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation. PMID- 27555772 TI - The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation. AB - Reductive drug-functionalized gold nanoparticles (AuNPs) have been proposed to enhance the damage of X-rays to cells through improving hydroxyl radical production by secondary electrons. In this work, polyethylene glycol-capped AuNPs were conjugated with tirapazamine (TPZ) moiety, and then thioctyl TPZ (TPZs) modified AuNPs (TPZs-AuNPs) were synthesized. The TPZs-AuNPs were characterized by transmission electron microscopy, ultraviolet-visible spectra, dynamic light scattering, and inductively coupled plasma mass spectrometry to have a size of 16.6+/-2.1 nm in diameter and a TPZs/AuNPs ratio of ~700:1. In contrast with PEGylated AuNPs, the as-synthesized TPZs-AuNPs exhibited 20% increment in hydroxyl radical production in water at 2.0 Gy, and 19% increase in sensitizer enhancement ratio at 10% survival fraction for human hepatoma HepG2 cells under X ray irradiation. The production of reactive oxygen species in HepG2 cells exposed to X-rays in vitro demonstrated a synergistic radiosensitizing effect of AuNPs and TPZ moiety. Thus, the reductive drug-conjugated TPZs-AuNPs as a kind of AuNP radiosensitizer with low gold loading provide a new strategy for enhancing the efficacy of radiation therapy. PMID- 27555773 TI - Aptamer-hybrid nanoparticle bioconjugate efficiently delivers miRNA-29b to non small-cell lung cancer cells and inhibits growth by downregulating essential oncoproteins. AB - MicroRNAs (miRNAs) are potentially attractive candidates for cancer therapy. However, their therapeutic application is limited by lack of availability of an efficient delivery system to stably deliver these potent molecules intracellularly to cancer cells while avoiding healthy cells. We developed a novel aptamer-hybrid nanoparticle bioconjugate delivery system to selectively deliver miRNA-29b to MUC1-expressing cancer cells. Significant downregulation of oncoproteins DNMT3b and MCL1 was demonstrated by these MUC1 aptamer functionalized hybrid nanoparticles in A549 cells. Furthermore, downregulation of these oncoproteins led to antiproliferative effect and induction of apoptosis in a superior version when compared with Lipofectamine 2000. This novel aptamer hybrid nanoparticle bioconjugate delivery system could potentially serve as a platform for intracellular delivery of miRNAs to cancer cells, hence improving the therapeutic outcome of lung cancer. PMID- 27555774 TI - Degradability, cytocompatibility, and osteogenesis of porous scaffolds of nanobredigite and PCL-PEG-PCL composite. AB - Biocomposite scaffolds were fabricated by incorporation of nanobredigite (n-BD) into the polymer of poly(epsilon-caprolactone)-poly(ethyleneglycol)-poly(epsilon caprolactone) (PCL-PEG-PCL). The results revealed that the addition of n-BD into PCL-PEG-PCL significantly improved water absorption, compressive strength, and degradability of the scaffolds of n-BD/PCL-PEG-PCL composite (n-BPC) compared with PCL-PEG-PCL scaffolds alone. In addition, the proliferation and alkaline phosphatase activity of MG63 cells cultured on n-BPC scaffolds were obviously higher than that cultured on PCL-PEG-PCL scaffolds. Moreover, the results of the histological evaluation from the animal model revealed that the n-BPC scaffolds significantly improved new bone formation compared with the PCL-PEG-PCL scaffolds, indicating good osteogenesis. The n-BPC scaffolds with good biocompatibility could stimulate cell proliferation, differentiation, and bone tissue regeneration and would be an excellent candidate for bone defect repair. PMID- 27555775 TI - Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment. AB - Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in ADHD patients with those in age matching controls, lower levels are found in ADHD patients' blood. omega-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that omega-3 PUFA supplements could have beneficial effects on ADHD. However, the results of omega 3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of omega-3 containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as "ADHD" and "omega-3/6 PUFA" and identified 25 studies that met the inclusion and exclusion criteria. The results of these omega 3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a omega-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with omega-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to omega-3 PUFA treatments and also to determine the optimal concentrations of omega-3 PUFAs, whether used as single treatment or in combination with other medication. PMID- 27555776 TI - Clinical characteristics of patients with benign nonlesional temporal lobe epilepsy. AB - PURPOSE: To evaluate the evolution of nonlesional temporal lobe epilepsy (TLE-NL) in patients treated exclusively with antiepileptic drugs and to elucidate clinical phenotypes related to the prognosis of these patients. METHODS: Clinical, radiological, and electroencephalographic (EEG) findings in 84 patients with TLE-NL were reviewed. A good response group (GRG) and a poor response group (PRG) were defined if the duration of their seizure-free period was >1 year, or <1 year, respectively. RESULTS: There were 46 (54.8%) patients in the GRG and 38 (45.2%) patients in the PRG. The number of antiepileptic drugs administered was significantly lower in the GRG than that in the PRG (1.3+/-0.8 vs 2.8+/-1.0, respectively; P<0.05). The GRG had a significantly older age of onset than the PRG and a lower occurrence of initial precipitating events, such as febrile seizures, central nervous system infection, and head trauma (P<0.05). The prevalence of EEG abnormality, presence of aura, generalized seizures, and automatism was less frequently observed in the GRG (P<0.05). Multivariate analysis showed that the presence of automatism and initial precipitating events were significantly associated with a poor prognosis (P<0.05). CONCLUSION: In contrast to the commonly assumed intractability of TLE, we found that more than 54% of patients with TLE-NL achieved a long seizure-free period. Older age at onset of TLE-NL was associated with a better prognosis. However, the presence of automatism and initial precipitating events were related to a poor prognosis. Future prospective studies with a much larger population are warranted. PMID- 27555777 TI - A bypass case due to an acute inferior myocardial infarction caused by vascular occlusion of the left subclavian artery and left anterior descending artery. AB - ST segment elevation is the most common electrocardiographic finding in acute myocardial infarction. ST elevation in chest leads generally represents left anterior descending artery occlusion, while elevation in DII and III, and aVF represents right coronary and circumflex artery occlusion. A female patient aged 66 years was admitted to our emergency service with ST elevation in leads DIII and aVF. A diagnosis of acute inferior myocardial infarction was made. The patient's history included coronary artery bypass graft involving the left internal mammary artery to the left anterior descending coronary artery and aorta to the right coronary artery. The patient was taken to the cardiac catheterization laboratory for primary percutaneous coronary intervention and a lesion in the left anterior descending artery was identified. Additionally, the left subclavian artery was totally occluded. Following intervention to the lesion, the patient was discharged on day 4 of admission. PMID- 27555778 TI - Repeated adjacent segment diseases and fractures in osteoporotic patients: a case report. AB - BACKGROUND: Pedicle screw instrumentation for treating spinal disorder is becoming increasingly widespread. Many studies have advocated its use to facilitate rigid fixation for spine; however, adjacent segmental disease is a known complication. Instrumented fusion for osteoporotic spines remains a significant challenge for spine surgeons. Prophylactic vertebroplasty for adjacent vertebra has been reported to reduce the complications of junctional compression fractures but has raised a new problem of vertebral subluxation. This case report is a rare and an extreme example with many surgical complications caused by repeated instrumented fusion for osteoporotic spine in a single patient. This patient had various complications including adjacent segmental disease, vertebral subluxation, and junctional fractures on radiographs and magnetic resonance images. CASE PRESENTATION: An 81-year-old Taiwanese woman underwent decompression and instrumented fusion of L4-L5 in Taiwan 10 years ago. Due to degenerative spinal stenosis of L3-L4 and L2-L3, she had decompression with instrumented fusion from L5 to L1 at the previous hospital. However, catastrophic vertebral subluxations with severe neurologic compromise occurred, and she underwent salvage surgeries twice with prolonged instrumented fusion from L5 to T2. The surgeries did not resolve her problems of spinal instability and neurologic complications. Eventually, the patient remained with a Frankel Grade C spinal cord injury. CONCLUSION: Adjacent segmental disease, junctional fracture, and vertebral subluxation are familiar complications following instrumented spinal fusion surgeries for osteoporotic spines. Neurologic injuries following long instrumentation are often serious and difficult to address with surgery alone. Conservative treatments should always be contemplated as an alternative method for patients with poor bone stock. PMID- 27555779 TI - A simple dietary assessment tool to monitor food intake of hospitalized adult patients. AB - BACKGROUND/OBJECTIVES: Monitoring food intake of patients during hospitalization using simple methods and minimal training is an ongoing problem in hospitals. Therefore, there is a need to develop and validate a simple, easy to use, and quick tool that enables staff to estimate dietary intake. Thus, this study aimed to develop and validate the Pictorial Dietary Assessment Tool (PDAT). SUBJECTS AND METHODS: A total of 37 health care staff members consisting of dietitians, nurses, and serving assistants estimated 130 breakfast and lunch meals consumed by 67 patients using PDAT. PDAT was developed based on the hospital menu that consists of staple food (rice or porridge), animal source protein (chicken, meat, eggs, and fish), and non-animal source protein (tau fu and tempeh), with a total of six pictorials of food at each meal time. Weighed food intake was used as a gold standard to validate PDAT. Agreement between methods was analyzed using correlations, paired t-test, Bland-Altman plots, kappa statistics, and McNemar's test. Sensitivity, specificity, and area under the curve of receiver operating characteristic were calculated to identify whether patients who had an inadequate food intake were categorized as at risk by the PDAT, based on the food weighing method. Agreement between different backgrounds of health care staff was calculated by intraclass correlation coefficient and analysis of variance test. RESULTS: There was a significant correlation between the weighing food method and PDAT for energy (r=0.919, P<0.05), protein (r=0.843, P<0.05), carbohydrate (r=0.912, P<0.05), and fat (r=0.952; P<0.05). Nutrient intakes as assessed using PDAT and food weighing were rather similar (295+/-163 vs 292+/-158 kcal for energy; 13.9+/-7.8 vs 14.1+/-8.0 g for protein; 46.1+/-21.4 vs 46.7+/-22.3 g for carbohydrate; 7.4+/-3.1 vs 7.4+/-3.1 g for fat; P>0.05). The PDAT and food weighing method showed a satisfactory agreement beyond chance (k) (0.81 for staple food and animal source protein; 0.735 for non-animal source protein). Intraclass correlation coefficient ranged between 0.91 and 0.96 among respondents. There were no differences in energy, protein, carbohydrate, and fat intake estimated among health care staff (P=0.967; P=0.951; P=0.888; P=0.847, respectively). CONCLUSION: In conclusion, PDAT provides a valid estimation of macronutrient consumption among hospitalized adult patients. PMID- 27555780 TI - Alpers-Huttenlocher syndrome: the role of a multidisciplinary health care team. AB - Alpers-Huttenlocher syndrome (AHS) is a mitochondrial DNA-depletion syndrome. Age of onset is bimodal: early onset at 2-4 years and later adolescent onset at 17-24 years of age. Early development is usually normal, with epilepsy heralding the disorder in ~50% of patients. The onset of seizures is coupled with progressive cognitive decline. Hepatopathy is variable, and when present is a progressive dysfunction leading to liver failure in many cases. These features of seizures, cognitive degeneration, and hepatopathy represent the "classic triad" of AHS. However, most patients develop other system involvement. Therefore, although AHS is ultimately a lethal disorder, medical care is required for sustained quality of life. Frequently, additional organ systems - gastrointestinal, respiratory, nutritional, and psychiatric - abnormalities appear and need treatment. Rarely, cardiovascular dysfunction and even pregnancy complicate medical treatment. Optimal care requires a team of physicians and caretakers to make sure quality of life is optimized. The care team, together with the family and palliative care specialists, need to be in communication as the disease progresses and medical changes occur. Although the unpredictable losses of function challenge medical care, the team approach can foster the individual quality-of-life care needed for the patient and family. PMID- 27555781 TI - Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposite. AB - The study describes an in situ green biosynthesis of zinc oxide nanocomposite using the seaweed Sargassum muticum water extract and hyaluronan biopolymer. The morphology and optical properties of the hyaluronan/zinc oxide (HA/ZnO) nanocomposite were determined by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and ultraviolet-vis analysis. Electron microscopy and X-ray diffraction analysis showed that the zinc oxide nanoparticles were polydispersed with a mean size of 10.2+/-1.5 nm. The nanoparticles were mostly hexagonal in crystalline form. The HA/ZnO nanocomposite showed the absorption properties in the ultraviolet zone that is ascribed to the band gap of zinc oxide nanocomposite. In the cytotoxicity study, cancer cells, pancreatic adenocarcinoma (PANC-1), ovarian adenocarcinoma (CaOV-3), colonic adenocarcinoma (COLO205), and acute promyelocytic leukemia (HL-60) cells were treated with HA/ZnO nanocomposite. At 72 hours of treatment, the half maximal inhibitory concentration (IC50) value via the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was 10.8+/-0.3 MUg/mL, 15.4+/-1.2 MUg/mL, 12.1+/-0.9 MUg/mL, and 6.25+/-0.5 MUg/mL for the PANC-1, CaOV-3, COLO-205, and HL 60 cells, respectively, showing that the composite is most toxic to the HL-60 cells. On the other hand, HA/ZnO nanocomposite treatment for 72 hours did not cause toxicity to the normal human lung fibroblast (MRC-5) cell line. Using fluorescent dyes and flow cytometry analysis, HA/ZnO nanocomposite caused G2/M cell cycle arrest and stimulated apoptosis-related increase in caspase-3 and -7 activities of the HL-60 cells. Thus, the study shows that the HA/ZnO nanocomposite produced through green synthesis has great potential to be developed into an efficacious therapeutic agent for cancers. PMID- 27555782 TI - Network analysis reveals potential markers for pediatric adrenocortical carcinoma. AB - Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein protein interaction (PPI) and gene-gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs microRNAs-transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID- 27555783 TI - miR-203 is involved in the laryngeal carcinoma pathogenesis via targeting VEGFA and Cox-2. AB - The development of laryngeal squamous cell carcinoma (LSCC) is a multistep process involving multiple factors. MicroRNAs, a group of important negative regulators of gene expression, have also been confirmed to be involved in the LSCC pathogenesis. In the present study, we compared the expression of nine selected microRNAs in the LSCC tissues and adjacent nontumor tissues. We found that the expression of miR-203 was significantly reduced in the LSCC tissues. Predicted by using bioinformatics tools, we found that VEGFA and cyclooxygenase-2 (Cox-2) may be direct targets of miR-203. By subsequent determination through dual-luciferase assay and Western blot, we confirmed that miR-203 suppresses the expression of VEGFA and Cox-2 by directly targeting 3'-untranslated region. Meanwhile, by analyzing the relationship between miR-203 and VEGFA in clinical tissue samples, we found that a negative correlation existed in the expression of miR-203 and VEGFA (P=0.0096, r=-0.33). Similarly, the expression of miR-203 and Cox-2 also has a negative correlation (P=0.0019, r=-0.46). Subsequently, in vitro functional study indicated that miR-203 played as a tumor suppressor by repressing proliferation, migration, and invasion of Hep-2 cells. The overexpression of VEGFA partially rescued the effect of overexpressed miR-203. Overexpressed Cox-2 partially rescued the effect of miR-203 on Hep-2 cell proliferation but not on the cell migration and invasion capacity. These findings suggest that miR-203 plays as a tumor suppressor in LSCC, partially by regulating VEGFA and Cox-2, and may serve as a potential target for therapeutic intervention. PMID- 27555784 TI - Efficacy of cisplatin/pemetrexed with bevacizumab to treat advanced lung adenocarcinoma with different drive genes: case report and literature review. AB - BACKGROUND: Bevacizumab combined with chemotherapy has become the first-line therapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). However, few studies have focused on cisplatin/pemetrexed with bevacizumab as the first-line therapy to treat advanced nonsquamous NSCLC. Importantly, whether the epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements can influence the efficacy of bevacizumab in combination with chemotherapy is very interesting. Herein, we report three cases with different types of gene drives in advanced nonsquamous NSCLC. CASE PRESENTATION: In the first case, a patient presented with wild-type EGFR and negative ALK rearrangement. In the second case, a patient presented with wild-type EGFR and positive ALK rearrangement. In the third case, a patient presented with negative ALK rearrangement and mutated EGFR in exon 19. CONCLUSION: We speculate that bevacizumab in combination with cisplatin/pemetrexed as the first-line therapy is well tolerated and results in a clinically meaningful treatment benefit, irrespective of the gene drive type in advanced nonsquamous NSCLC. However, more data are needed to confirm the relationship. PMID- 27555785 TI - Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients. AB - Long noncoding RNAs have been documented as having widespread roles in carcinogenesis and cancer progression. However, roles of long noncoding RNAs in osteosarcoma remain unclear. This study is to investigate the clinical relevance and biological functions of long noncoding RNA 91H in osteosarcoma. Herein, we confirmed that 91H expression was notably increased in osteosarcoma patients and cell lines compared to healthy controls and normal human bone cell lines. High expression of 91H was significantly correlated with advanced clinical stage, chemotherapy after surgery, and tumor size >5 cm. Furthermore, 91H was an independent prognostic factor for overall survival in osteosarcoma patients after treatments. Additionally, the knockdown of 91H expression inhibited osteosarcoma cells' proliferation and promoted their apoptosis in vitro. In summary, these findings indicate that 91H may be a novel biomarker for risk prognostication and also provide a clue to the molecular etiology of osteosarcoma. PMID- 27555786 TI - Potential predictive role of chemotherapy-induced changes of soluble CD40 ligand in untreated advanced pancreatic ductal adenocarcinoma. AB - Pancreas ductal adenocarcinoma lacks predictive biomarkers. CD40 is a member of the tumor necrosis factor superfamily. CD40-sCD40L interaction is considered to contribute to the promotion of tumor cell growth and angiogenesis. The aim of the present study was to investigate the role of serum sCD40L as a predictor in metastatic pancreatic cancer. We evaluated 27 consecutive pancreatic cancer patients treated with FOLFIRINOX (21 patients) or gemcitabine plus nab-paclitaxel combination (six patients). The sCD40L level was measured in serum by enzyme linked immunosorbent assay at baseline, at first evaluation (all patients), and at time to progression (18 patients). The radiological response was evaluated according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. The Wilcoxon signed-rank test was used to compare pre-post treatment sCD40L levels with respect to clinical response, while Pearson's correlation coefficient was used for the correlation between sCD40L and CA19.9 pre- and post-treatment. The Kruskal-Wallis test was also conducted for further comparisons. We observed a statistically significant reduction in the sCD40L level after 3 months of treatment in patients with partial response (11,718.05+/-7,097.13 pg/mL vs 4,689.42+/-5,409.96 pg/mL; P<0.01). Conversely, in patients with progressive disease, the biomarker statistically increased in the same time (9,351.51+/ 7,356.91 pg/mL vs 22,282.92+/-11,629.35 pg/mL; P<0.01). This trend of sCD40L was confirmed in 18 patients at time to progression after the first evaluation. No differences were recorded within the stable disease group. Moreover, there was a positive correlation between the sCD40L and CA19.9 pre-post treatment variation percentage (Pearson's correlation coefficient =0.52; P<0.05). Our data suggest a possible predictive role of sCD40L in pancreatic cancer patients, similar to CA19.9. PMID- 27555787 TI - The impact of the extent of surgical resection on survival of gastric cancer patients. AB - OBJECTIVE: The aim of this study was to examine the significance of the extent of gastric resection on the postoperative and overall gastric cancer survival. BACKGROUND: Resection with clean margins (4 cm or more) is widely accepted as the standard-ized goal for radical treatment of gastric cancer according to current guidelines, while the type of resection (subtotal or total) is still a matter of debate. PATIENTS AND METHODS: The study included 155 patients diagnosed and treated in the Department of Surgery, Aleksandrovska University Hospital between January 2005 and December 2014. In order to determine the significance of the resection volume, we excluded from the study 54 patients receiving palliative intervention or staging exploratory laparoscopy. The remaining 101 patients were divided into two groups based on the volume of the performed gastric resection (total and subtotal) and compared based on overall survival and perioperative mortality. We also investigated the 3-year survival in the two groups as well as the overall survival only in the subgroup of patients with D2 lymphadenectomy. RESULTS: We could not determine any statistically significant difference in overall survival and 3-year survival (P=0.990) based on the extent of surgical resection (P=0.824) or perioperative mortality. The statistical analysis on patients with D2 lymph node dissection only did not show significance for overall survival. CONCLUSION: Our study shows no difference in safety and long-term survival rate of patients with gastric carcinoma based on the volume of stomach resection. Comparison with other studies also shows no difference in survival based on volume of the resection. PMID- 27555788 TI - Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy. AB - PURPOSE: Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%-45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions. PATIENTS AND METHODS: Twenty-four paired primary and corresponding metastatic tissue samples from eight nonresponding and four responding metastatic colorectal cancer patients treated with cetuximab-based therapy were sequenced using a next-generation sequencing panel of 26 genes involved in EGFR signaling pathway and colorectal carcinogenesis. RESULTS: Mutational status of primary tumors and metastatic lesions was highly concordant in TP53, APC, CTNNB1, KRAS, PIK3CA, PTEN, and FBXW7 genes. Metastatic samples harbor significantly more mutations than primary tumors. Potentially negative predictive value of FBXW7 mutations in relationship to anti-EGFR treatment outcomes was confirmed. Finally, new occurrences of activating KRAS mutations were identified in a group of patients initially determined as wild-type RAS by routinely used qPCR-based RAS mutational tests. All newly detected activating KRAS mutations most likely led to cetuximab treatment failure. CONCLUSION: The results of the present study suggest a need of careful consideration of previously published results of anti-EGFR targeted therapy with regard to potentially inaccurate diagnostic tools used in the past. Based on our findings, we recommend more extensive use of next generation sequencing testing in daily clinical practice, as it brings a significant added value in terms of validity of the diagnostic procedure. PMID- 27555789 TI - Characterizing individual painDETECT symptoms by average pain severity. AB - BACKGROUND: painDETECT is a screening measure for neuropathic pain. The nine-item version consists of seven sensory items (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure), a pain course pattern item, and a pain radiation item. The seven-item version consists only of the sensory items. Total scores of both versions discriminate average pain-severity levels (mild, moderate, and severe), but their ability to discriminate individual item severity has not been evaluated. METHODS: Data were from a cross-sectional, observational study of six neuropathic pain conditions (N=624). Average pain severity was evaluated using the Brief Pain Inventory-Short Form, with severity levels defined using established cut points for distinguishing mild, moderate, and severe pain. The Wilcoxon rank sum test was followed by ridit analysis to represent the probability that a randomly selected subject from one average pain-severity level had a more favorable outcome on the specific painDETECT item relative to a randomly selected subject from a comparator severity level. RESULTS: A probability >50% for a better outcome (less severe pain) was significantly observed for each pain symptom item. The lowest probability was 56.3% (on numbness for mild vs moderate pain) and highest probability was 76.4% (on cold/heat for mild vs severe pain). The pain radiation item was significant (P<0.05) and consistent with pain symptoms, as well as with total scores for both painDETECT versions; only the pain course item did not differ. CONCLUSION: painDETECT differentiates severity such that the ability to discriminate average pain also distinguishes individual pain item severity in an interpretable manner. Pain-severity levels can serve as proxies to determine treatment effects, thus indicating probabilities for more favorable outcomes on pain symptoms. PMID- 27555790 TI - Work intensity in sacroiliac joint fusion and lumbar microdiscectomy. AB - BACKGROUND: The evidence base supporting minimally invasive sacroiliac (SI) joint fusion (SIJF) surgery is increasing. The work relative value units (RVUs) associated with minimally invasive SIJF are seemingly low. To date, only one published study describes the relative work intensity associated with minimally invasive SIJF. No study has compared work intensity vs other commonly performed spine surgery procedures. METHODS: Charts of 192 patients at five sites who underwent either minimally invasive SIJF (American Medical Association [AMA] CPT(r) code 27279) or lumbar microdiscectomy (AMA CPT(r) code 63030) were reviewed. Abstracted were preoperative times associated with diagnosis and patient care, intraoperative parameters including operating room (OR) in/out times and procedure start/stop times, and postoperative care requirements. Additionally, using a visual analog scale, surgeons estimated the intensity of intraoperative care, including mental, temporal, and physical demands and effort and frustration. Work was defined as operative time multiplied by task intensity. RESULTS: Patients who underwent minimally invasive SIJF were more likely female. Mean procedure times were lower in SIJF by about 27.8 minutes (P<0.0001) and mean total OR times were lower by 27.9 minutes (P<0.0001), but there was substantial overlap across procedures. Mean preservice and post-service total labor times were longer in minimally invasive SIJF (preservice times longer by 63.5 minutes [P<0.0001] and post-service labor times longer by 20.2 minutes [P<0.0001]). The number of postoperative visits was higher in minimally invasive SIJF. Mean total service time (preoperative + OR time + postoperative) was higher in the minimally invasive SIJF group (261.5 vs 211.9 minutes, P<0.0001). Intraoperative intensity levels were higher for mental, physical, effort, and frustration domains (P<0.0001 each). After taking into account intensity, intraoperative workloads showed substantial overlap. CONCLUSION: Compared to a commonly performed lumbar spine surgical procedure, lumbar microdiscectomy, that currently has a higher work RVU, preoperative, intraoperative, and postoperative workload for minimally invasive SIJF is higher. The work RVU for minimally invasive SIJF should be adjusted upward as the relative amount of work is comparable. PMID- 27555791 TI - Effects of vildagliptin relative to sulfonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: influence of age and treatment with/without metformin in the VIRTUE study. AB - BACKGROUND: VIRTUE was a prospective, observational study assessing the effectiveness and safety of vildagliptin vs sulfonylureas (SUs) (both as monotherapy and in combination with metformin) in patients with type 2 diabetes mellitus who fasted during Ramadan. A post hoc analysis was carried out to assess the effect of treatment with/without metformin and age (<65 years or >=65 years). PATIENTS AND METHODS: Patients were recruited from the Middle East and Asia. The primary end point was proportion of patients with one or more hypoglycemic event (HE) during Ramadan. Secondary end points included change from baseline in glycated hemoglobin (HbA1c), body weight, and safety. RESULTS: Overall, 684 patients received vildagliptin and 631 received SUs. Most patients received dual therapy with metformin (n=1,148) and were aged <65 years (n=1,189). A few patients experienced one or more HE with vildagliptin vs SU monotherapy (6.5% vs 14.5%) and with vildagliptin + metformin vs SUs + metformin (5.3% vs 20.6%); the latter achieved statistical significance (P<0.001) in both age subgroups (<65 years: 5.5% vs 18.4%, P<0.001; >=65 years: 2.8% vs 30.9%, P<0.001). Vildagliptin was associated with numerically greater HbA1c and body weight reductions vs SUs, regardless of the therapy type or age. A higher proportion of SU- vs vildagliptin treated patients experienced adverse events across all subgroups. CONCLUSION: A few patients experienced HEs with vildagliptin vs SUs regardless of age, and in patients on dual therapy. Vildagliptin +/- metformin was also associated with good glycemic and weight control and was well tolerated. Vildagliptin might be a useful treatment option for patients with type 2 diabetes mellitus, particularly high-risk populations such as the elderly fasting during Ramadan. PMID- 27555792 TI - Translational and clinical perspectives on sphincter of Oddi dysfunction. AB - Sphincter of Oddi dysfunction is a complex pathophysiologic entity that is associated with significant morbidity causing abdominal pain, nausea, and vomiting. The purpose of this review is to describe the anatomy and physiology of the sphincter of Oddi, to understand the pathologic mechanisms thought to be responsible for symptomatology, review recent major studies, explore endoscopic and pharmacologic therapies and their efficacy, and to explore future research avenues. PMID- 27555794 TI - Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype. AB - BACKGROUND: Previous studies on genetic testing of chromosomal abnormalities in individuals diagnosed with autism spectrum disorder (ASD) found that ~80% have negative genetic test results (NGTRs) and ~20% have positive genetic test results (PGTRs), of which ~7% were probable de novo mutations (PDNMs). Research suggests that parental age is a risk factor for an ASD diagnosis. This study examined genotypic variation in ASD and its relationship to parental age and phenotype. METHODS: Phenotype was derived from detailed clinical information, and genotype was derived from high-resolution blood chromosome and blood whole-genome copy number variant genetic testing on a consecutive cohort (born: 1983-2009) of subjects diagnosed with ASD (N=218). RESULTS: Among the subjects examined, 80.3% had NGTRs and 19.7% had PGTRs, of which 6.9% had PDNMs. NGTR subjects were born more recently (the risk of PDNMs decreasing by 12% per more recent birth year) and tended to have an increased male-female ratio compared to PDNM subjects. PDNM subjects had significantly increased mean parental age and paternal age at subject's birth (the risk of a PDNM increasing by 7%-8% per year of parental or paternal age) compared to NGTR subjects. PGTR and NGTR subjects showed significant improvements in speech/language/communication with increasing age. PGTR subjects showed significant improvements in sociability, a core feature of an ASD diagnosis, with increasing age, whereas NGTR subjects showed significant worsening in sociability with increasing age. CONCLUSION: This study helps to elucidate different phenotypic ASD subtypes and may even indicate the need for differential diagnostic classifications. PMID- 27555793 TI - Hereditary pancreatitis: current perspectives. AB - Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. PMID- 27555795 TI - Does a medical history of hypertension influence disclosing genetic testing results of the risk for salt-sensitive hypertension, in primary care? AB - OBJECTIVE: Disclosing genetic testing results may contribute to the prevention and management of many common diseases. However, whether the presence of a disease influences these effects is unclear. This study aimed to clarify the difference in the effects of disclosing genetic testing results of the risk for developing salt-sensitive hypertension on the behavioral modifications with respect to salt intake in hypertensive and nonhypertensive patients. METHODS: A cross-sectional study using a self-administered questionnaire was conducted for outpatients aged >20 years (N=2,237) at six primary care clinics and hospitals in Japan. The main factors assessed were medical histories of hypertension, salt preferences, reduced salt intakes, and behavior modifications for reducing salt intake. Behavioral modifications of participants were assessed using their behavior stages before and after disclosure of the hypothetical genetic testing results. RESULTS: Of the 2,237 participants, 1,644 (73.5%) responded to the survey. Of these respondents, 558 (33.9%) patients were hypertensive and 1,086 (66.1%) were nonhypertensive. After being notified of the result "If with genetic risk", the nonhypertensive participants were more likely to make positive behavioral modifications compared to the hypertensive patients among all participants and in those aged <65 years (adjusted relative ratio [ad-RR], 1.76; 95% confidence interval, 1.12-2.76 and ad-RR, 1.99; 1.11-3.57, respectively). In contrast, no difference in negative behavioral modifications between hypertensive and nonhypertensive patients was detected after being notified of the result "If without genetic risk" (ad-RR, 1.05; 95% confidence interval, 0.70-1.57). CONCLUSION: The behavior of modifying salt intake after disclosure of the genetic testing results differed between hypertensive and nonhypertensive patients. Disclosing a genetic risk for salt-sensitive hypertension was likely to cause nonhypertensive patients, especially those aged <65 years, to improve their behavior regarding salt intake. We conclude that disclosing genetic testing results could help prevent hypertension, and that the doctor should communicate the genetic testing results to those patients with a medical history of hypertension, or those who are at risk of developing hypertension. PMID- 27555796 TI - Efficacy of stereotactic gamma knife surgery and microvascular decompression in the treatment of primary trigeminal neuralgia: a retrospective study of 220 cases from a single center. AB - OBJECTIVES: A retrospective study was undertaken to compare the efficacy of stereotactic gamma knife surgery (GKS) and microvascular decompression (MVD) in the treatment of primary trigeminal neuralgia (TN) at a single center. The study included the evaluation of clinical outcomes of pain relief and pain recurrence and complications associated with GKS and MVD. METHODS: The study included 202 patients with primary TN and was conducted between January 2013 and December 2014; about 115 patients were treated with GKS and 87 patients were treated with MVD. TN pain was evaluated using the Barrow Neurological Institute and the visual analog scale scoring systems. Preoperative magnetic resonance tomographic angiography was performed for all patients. Microscope-assisted MVD used the suboccipital retrosigmoid sinus approach. GKS targeted the trigeminal nerve root entry zone with a margin radiation dose of 59.5 Gy, and brainstem dose <12 Gy. Posttreatment follow-up was for 2 years. RESULTS: Postoperative Barrow Neurological Institute scores for patients treated with GKS and MVD were significantly improved compared with preoperative scores (P<0.01). Reduction in postoperative pain following MVD (95.4% patients) was significantly greater than that following GKS (88.7% patients) (P<0.01). Postoperative visual analog scale scores of the MVD group were significantly reduced compared with those of patients treated with GKS at the same postoperative time points (P<0.01). Patients treated with GKS had a significantly increased rate of loss of corneal reflex compared with patients treated with MVD (P=0.002). CONCLUSION: Both GKS and MVD are safe and effective first-line and adjunctive treatment options for patients with TN. The clinical outcomes of pain relief and reduction of pain recurrence were better with MVD. For GKS, this study showed that the optimal radiation therapeutic dose range was 70-90 Gy, but brainstem radiation protection is recommended. PMID- 27555797 TI - Current best practice in the management of hypertensive disorders in pregnancy. AB - Preeclampsia is a potentially serious complication of pregnancy with increasing significance worldwide. Preeclampsia is the cause of 9%-26% of global maternal mortality and a significant proportion of preterm delivery, and maternal and neonatal morbidity. Incidence is increasing in keeping with the increase in obesity, maternal age, and women with medical comorbidities entering pregnancy. Recent developments in the understanding of the pathophysiology of preeclampsia have opened new avenues for prevention, screening, and management of this condition. In addition it is known that preeclampsia is a risk factor for cardiovascular disease in both the mother and the child and presents an opportunity for early preventative measures. New tools for early detection, prevention, and management of preeclampsia have the potential to revolutionize practice in the coming years. This review presents the current best practice in diagnosis and management of preeclampsia and the hypertensive disorders of pregnancy. PMID- 27555798 TI - Idiopathic horseshoe-like macular tear: a case report. AB - BACKGROUND: Although a few cases with idiopathic horseshoe-like macular tear have been reported, the mechanism remains unknown and a standard treatment has yet to be determined. OBJECTIVE: To report the outcome for a patient with idiopathic horseshoe-like macular tear who underwent vitreous surgery. CASE REPORT: A 65 year-old man with no previous injury or ophthalmic disease presented with abnormal vision in his left eye. Best-corrected visual acuity was 0.8 in the right and 0.3 in the left, and the relative afferent pupillary defect was negative. Ophthalmoscopy revealed a horseshoe-like tear on the temporal side of the macula in the left eye. The tear size was 0.75 disc diameters (DD). Optical coherence tomography showed that the focal retinal detachment reached the fovea. A few days after the first visit, there was no longer adhesion of the flap of the tear to the retina and the tear size had increased to 1.5 DD. The patient underwent vitreous surgery similar to large macular hole surgery, with the tear closure repaired using the inverted internal limiting membrane flap technique with 20% SF6 gas tamponade. Although the tear decreased to 0.5 DD after the surgery, complete closure of the tear was not achieved. CONCLUSION: While cases with horseshoe-like macular tear following trauma and branch retinal vein occlusion have been reported, to the best of our knowledge, this is the first reported idiopathic case. In the present case, there was expansion of the tear until the patient actually underwent surgery. If vertical vitreous traction indeed plays a role in horseshoe-like macular tears, this will need to be taken into consideration at the time of the vitreous surgery in these types of cases. PMID- 27555799 TI - Myoelectric control of prosthetic hands: state-of-the-art review. AB - Myoelectric signals (MES) have been used in various applications, in particular, for identification of user intention to potentially control assistive devices for amputees, orthotic devices, and exoskeleton in order to augment capability of the user. MES are also used to estimate force and, hence, torque to actuate the assistive device. The application of MES is not limited to assistive devices, and they also find potential applications in teleoperation of robots, haptic devices, virtual reality, and so on. The myoelectric control-based prosthetic hand aids to restore activities of daily living of amputees in order to improve the self esteem of the user. All myoelectric control-based prosthetic hands may not have similar operations and exhibit variation in sensing input, deciphering the signals, and actuating prosthetic hand. Researchers are focusing on improving the functionality of prosthetic hand in order to suit the user requirement with the different operating features. The myoelectric control differs in operation to accommodate various external factors. This article reviews the state of the art of myoelectric prosthetic hand, giving description of each control strategy. PMID- 27555801 TI - Medicine reclassification processes and regulations for proper use of over-the counter self-care medicines in Japan. AB - OBJECTIVES: Japan has actively reclassified substances ranging from prescription drugs to over-the-counter (OTC) drugs in recent years. The sale of most OTC drugs was deregulated several times and pharmacists' supervision was deemed no longer mandatory. Japan established a new OTC evaluation system in 2015 to hear opinions from various stakeholders regarding medicine types to be reclassified. This study aimed to examine the new framework to identify candidate substances for reclassification. Moreover, we examined how to manage the safe, self-care use of OTC drugs in Japan. METHODS: The necessary regulatory information on OTC approvals as of January 2015 was collected using an Internet search and relevant databases. To highlight the characteristics of OTC drugs in Japan, the UK was selected as a comparison country because it too was actively promoting the reclassification of medicines from prescription to nonprescription status, and because of economic similarity. RESULTS: Japan and the UK have a risk-based classification for nonprescription medicines. Japan has made OTC drugs available with mandatory pharmacists' supervision, face-to-face with pharmacists, or online instruction, which is similar to the "pharmacy medicine" practiced in the UK. Japan recently reformed the reclassification process to involve physicians and the public in the process; some interactions were back to "prescription-only medicine" in the UK. CONCLUSION: It is expected that the opinion of marketers, medical professionals, and the public will improve the discussion that will greatly contribute to the safe use of drugs. Monitoring the new system will be noteworthy to ensure that OTC drug users are managing their self-care properly and visiting a doctor only when necessary. The supply methods are similar in Japan and the UK; however, the expected growth in the Japanese OTC market by the Cabinet and the industry is still uncertain. PMID- 27555800 TI - Idiopathic noncirrhotic portal hypertension: current perspectives. AB - The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. PMID- 27555802 TI - Clinical predictors of central sleep apnea evoked by positive airway pressure titration. AB - PURPOSE: Treatment-emergent central sleep apnea (TECSA), also called complex apnea, occurs in 5%-15% of sleep apnea patients during positive airway pressure (PAP) therapy, but the clinical predictors are not well understood. The goal of this study was to explore possible predictors in a clinical sleep laboratory cohort, which may highlight those at risk during clinical management. METHODS: We retrospectively analyzed 728 patients who underwent PAP titration (n=422 split night; n=306 two-night). Demographics and self-reported medical comorbidities, medications, and behaviors as well as standard physiological parameters from the polysomnography (PSG) data were analyzed. We used regression analysis to assess predictors of binary presence or absence of central apnea index (CAI) >=5 during split-night PSG (SN-PSG) versus full-night PSG (FN-PSG) titrations. RESULTS: CAI >=5 was present in 24.2% of SN-PSG and 11.4% of FN-PSG patients during titration. Male sex, maximum continuous positive airway pressure, and use of bilevel positive airway pressure were predictors of TECSA, and rapid eye movement dominance was a negative predictor, for both SN-PSG and FN-PSG patients. Self reported narcotics were a positive predictor of TECSA, and the time spent in stage N2 sleep was a negative predictor only for SN-PSG patients. Self-reported history of stroke and the CAI during the diagnostic recording predicted TECSA only for FN-PSG patients. CONCLUSION: Clinical predictors of treatment-evoked central apnea spanned demographic, medical history, sleep physiology, and titration factors. Improved predictive models may be increasingly important as diagnostic and therapeutic modalities move away from the laboratory setting, even as PSG remains the gold standard for characterizing primary central apnea and TECSA. PMID- 27555803 TI - Student-centered tutoring as a model for patient-centeredness and empathy. AB - BACKGROUND: Curriculum planners and medical teachers attempt to enhance medical students' empathy and patient-centeredness. Despite educational efforts, there is stability in medical students' empathy and patient-centered medicine during the preclinical stage and a decline in both of them throughout the clinical years. Student-tutor relationship plays a key role in students' learning. This study tests the effect of learner-centered tutoring on students' empathy, patient centeredness, and behavior. PARTICIPANTS AND METHODS: The cohort of 55 students was divided into groups of seven or eight. The experimental group's tutors underwent LC mentoring. Empathy was assessed with the Jefferson Scale of Physician Empathy for Students; PC attitude was assessed with the Patient Provider Orientation Scale (PPOS). Behavior was assessed by simulations of doctor patient encounters with 32 students at the end of the third year. Each student participated in three such simulations, during which we analyzed ten aspects of physician-patient communication via Roter interaction analysis system (RIAS) coded audiotapes. RESULTS: A significant group difference was found for three RIAS categories: building a relationship and patient-centeredness, where the mean percentage of the experimental group was significantly higher than that of the control group, and gathering data, where the mean percentage of the experimental group was significantly lower than that of the control group. A significant correlation was found in the experimental group between empathy and positive talk and between PPOS and three of the RIAS categories: gathering data, psychosocial talk, and patient-centeredness. A significant negative correlation was found in the experimental group between PPOS and two of the RIAS categories: negative talk and doctor-centeredness. Two significant negative correlations were found in the control group: between empathy and patient-centeredness and PPOS and negative talk. CONCLUSION: The LC approach supports two of the RIAS categories, corresponding to clinical empathy and PC care and the link between certain behaviors and the PPOS. PMID- 27555804 TI - Monocyte chemoattractant protein-1 is not required for liver regeneration after partial hepatectomy. AB - BACKGROUND: Liver regeneration following 70 % partial hepatectomy (PH) requires the coordinated expression of soluble mediators produced by macrophages. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulus of monocyte recruitment and macrophage activation. The goal of this study was to determine how MCP-1 contributes to liver regeneration. METHODS: PH was performed on anesthetized C57Bl/6 (wild type) and MCP-1 knockout mice, and macrophage-produced cytokines and hepatocyte proliferation were measured. RESULTS: In wild type mice, hepatic MCP-1 protein levels increased 4-6 h after PH, and elevated plasma MCP-1 levels were detected 12 h after PH. Hepatocyte proliferation was comparable in MCP-1 knockout and wild type mice, as was the expression of macrophage-derived cytokines, TNFalpha and IL-6, and levels of phosphorylated STAT3. The number of CCR2(+) cells in the liver was similar in MCP-1 knockout and wild type mice, which suggests that other chemokines may recruit CCR2(+) cells in the absence of MCP-1. Studies with CCR2 knockout mice revealed that hepatocyte proliferation was suppressed ~40 % compared to wild type mice 36 h after PH, but proliferation and liver-body-weight ratios were similar at 48 h. CONCLUSION: These findings suggest that MCP-1 is not required for PH-induced liver regeneration, yet the role of CCR2 warrants further study. PMID- 27555805 TI - Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton. AB - Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation and antigravity assistance augments upper limb function and brain activity during rehabilitation exercises and may thus provide a novel restorative framework for severely affected stroke patients. PMID- 27555806 TI - Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization. AB - Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life. PMID- 27555807 TI - Caffeine Taste Signaling in Drosophila Larvae. AB - The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors. PMID- 27555808 TI - The Frequency-Dependent Neuronal Length Constant in Transcranial Magnetic Stimulation. AB - BACKGROUND: The behavior of the dendritic or axonal membrane voltage due to transcranial magnetic stimulation (TMS) is often modeled with the one-dimensional cable equation. For the cable equation, a length constant lambda0 is defined; lambda0 describes the axial decay of the membrane voltage in the case of constant applied electric field. In TMS, however, the induced electric field waveform is typically a segment of a sinusoidal wave, with characteristic frequencies of the order of several kHz. OBJECTIVE: To show that the high frequency content of the stimulation pulse causes deviations in the spatial profile of the membrane voltage as compared to the steady state. METHODS: We derive the cable equation in complex form utilizing the complex frequency-dependent representation of the membrane conductivity. In addition, we define an effective length constant lambdaeff, which governs the spatial decay of the membrane voltage. We model the behavior of a dendrite in an applied electric field oscillating at 3.9 kHz with the complex cable equation and by solving the traditional cable equation numerically. RESULTS: The effective length constant decreases as a function of frequency. For a model dendrite or axon, for which lambda0 = 1.5 mm, the effective length constant at 3.9 kHz is decreased by a factor 10 to 0.13 mm. CONCLUSION: The frequency dependency of the neuronal length constant has to be taken into account when predicting the spatial behavior of the membrane voltage as a response to TMS. PMID- 27555809 TI - Assembly of Neuronal Connectivity by Neurotrophic Factors and Leucine-Rich Repeat Proteins. AB - Proper function of the nervous system critically relies on sophisticated neuronal networks interconnected in a highly specific pattern. The architecture of these connections arises from sequential developmental steps such as axonal growth and guidance, dendrite development, target determination, synapse formation and plasticity. Leucine-rich repeat (LRR) transmembrane proteins have been involved in cell-type specific signaling pathways that underlie these developmental processes. The members of this superfamily of proteins execute their functions acting as trans-synaptic cell adhesion molecules involved in target specificity and synapse formation or working in cis as cell-intrinsic modulators of neurotrophic factor receptor trafficking and signaling. In this review, we will focus on novel physiological mechanisms through which LRR proteins regulate neurotrophic factor receptor signaling, highlighting the importance of these modulatory events for proper axonal extension and guidance, tissue innervation and dendrite morphogenesis. Additionally, we discuss few examples linking this set of LRR proteins to neurodevelopmental and psychiatric disorders. PMID- 27555810 TI - Systems Biology, Neuroimaging, Neuropsychology, Neuroconnectivity and Traumatic Brain Injury. AB - The patient who sustains a traumatic brain injury (TBI) typically undergoes neuroimaging studies, usually in the form of computed tomography (CT) and magnetic resonance imaging (MRI). In most cases the neuroimaging findings are clinically assessed with descriptive statements that provide qualitative information about the presence/absence of visually identifiable abnormalities; though little if any of the potential information in a scan is analyzed in any quantitative manner, except in research settings. Fortunately, major advances have been made, especially during the last decade, in regards to image quantification techniques, especially those that involve automated image analysis methods. This review argues that a systems biology approach to understanding quantitative neuroimaging findings in TBI provides an appropriate framework for better utilizing the information derived from quantitative neuroimaging and its relation with neuropsychological outcome. Different image analysis methods are reviewed in an attempt to integrate quantitative neuroimaging methods with neuropsychological outcome measures and to illustrate how different neuroimaging techniques tap different aspects of TBI-related neuropathology. Likewise, how different neuropathologies may relate to neuropsychological outcome is explored by examining how damage influences brain connectivity and neural networks. Emphasis is placed on the dynamic changes that occur following TBI and how best to capture those pathologies via different neuroimaging methods. However, traditional clinical neuropsychological techniques are not well suited for interpretation based on contemporary and advanced neuroimaging methods and network analyses. Significant improvements need to be made in the cognitive and behavioral assessment of the brain injured individual to better interface with advances in neuroimaging-based network analyses. By viewing both neuroimaging and neuropsychological processes within a systems biology perspective could represent a significant advancement for the field. PMID- 27555811 TI - Moving Forward by Stimulating the Brain: Transcranial Direct Current Stimulation in Post-Stroke Hemiparesis. AB - Stroke remains a leading cause of disability worldwide, with a majority of survivors experiencing long term decrements in motor function that severely undermine quality of life. While many treatment approaches and adjunctive strategies exist to remediate motor impairment, many are only efficacious or feasible for survivors with active hand and wrist function, a population who constitute only a minority of stroke survivors. Transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation, has been increasingly utilized to increase motor function following stroke as it is able to be used with stroke survivors of varying impairment levels, is portable, is relatively inexpensive and has few side effects and contraindications. Accordingly, in recent years the number of studies investigating its efficacy when utilized as an adjunct to motor rehabilitation regimens has drastically increased. While many of these trials have reported positive and promising efficacy, methodologies vary greatly between studies, including differences in stimulation parameters, outcome measures and the nature of physical practice. As such, an urgent need remains, centering on the need to investigate these methodological differences and synthesize the most current evidence surrounding the application of tDCS for post-stroke motor rehabilitation. Accordingly, the purpose of this paper is to provide a detailed overview of the most recent tDCS literature (published 2014-2015), while highlighting these variations in methodological approach, as well to elucidate the mechanisms associated with tDCS and post-stroke motor re-learning and neuroplasticity. PMID- 27555813 TI - Mild Developmental Foreign Accent Syndrome and Psychiatric Comorbidity: Altered White Matter Integrity in Speech and Emotion Regulation Networks. AB - Foreign accent syndrome (FAS) is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS) the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, and schizophrenia) as well as in developmental disorders (specific language impairment, apraxia of speech). In the present study, two adult males, one with atypical phonetic production and the other one with cluttering, reported having developmental FAS (DFAS) since their adolescence. Perceptual analysis by naive judges could not confirm the presence of foreign accent, possibly due to the mildness of the speech disorder. However, detailed linguistic analysis provided evidence of prosodic and segmental errors previously reported in AFAS cases. Cognitive testing showed reduced communication in activities of daily living and mild deficits related to psychiatric disorders. Psychiatric evaluation revealed long-lasting internalizing disorders (neuroticism, anxiety, obsessive-compulsive disorder, social phobia, depression, alexithymia, hopelessness, and apathy) in both subjects. Diffusion tensor imaging (DTI) data from each subject with DFAS were compared with data from a group of 21 age- and gender-matched healthy control subjects. Diffusion parameters (MD, AD, and RD) in predefined regions of interest showed changes of white matter microstructure in regions previously related with AFAS and psychiatric disorders. In conclusion, the present findings militate against the possibility that these two subjects have FAS of psychogenic origin. Rather, our findings provide evidence that mild DFAS occurring in the context of subtle, yet persistent, developmental speech disorders may be associated with structural brain anomalies. We suggest that the simultaneous involvement of speech and emotion regulation networks might result from disrupted neural organization during development, or compensatory or maladaptive plasticity. Future studies are required to examine whether the interplay between biological trait-like diathesis (shyness, neuroticism) and the stressful experience of living with mild DFAS lead to the development of internalizing psychiatric disorders. PMID- 27555814 TI - Speech Discrimination Difficulties in High-Functioning Autism Spectrum Disorder Are Likely Independent of Auditory Hypersensitivity. AB - Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive behaviors, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD) individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support the argument that an attentional deficit, rather than a perceptual deficit, affects the ability of individuals with ASD to discriminate speech from background noise. Finally, we piloted a novel questionnaire that measures difficulty hearing in noisy environments, and sensitivity to non-verbal and verbal sounds. Psychometric analysis using 128 TD participants provided novel evidence for a difference in sensitivity to non-verbal and verbal sounds, and these findings were reinforced by participants with ASD who also completed the questionnaire. The study was limited by a small and high-functioning sample of participants with ASD. Future work could test larger sample sizes and include lower-functioning ASD participants. PMID- 27555812 TI - Microglial Priming and Alzheimer's Disease: A Possible Role for (Early) Immune Challenges and Epigenetics? AB - Neuroinflammation is thought to contribute to Alzheimer's disease (AD) pathogenesis that is, to a large extent, mediated by microglia. Given the tight interaction between the immune system and the brain, peripheral immune challenges can profoundly affect brain function. Indeed, both preclinical and clinical studies have indicated that an aberrant inflammatory response can elicit behavioral impairments and cognitive deficits, especially when the brain is in a vulnerable state, e.g., during early development, as a result of aging, or under disease conditions like AD. However, how exactly peripheral immune challenges affect brain function and whether this is mediated by aberrant microglial functioning remains largely elusive. In this review, we hypothesize that: (1) systemic immune challenges occurring during vulnerable periods of life can increase the propensity to induce later cognitive dysfunction and accelerate AD pathology; and (2) that "priming" of microglial cells is instrumental in mediating this vulnerability. We highlight how microglia can be primed by both neonatal infections as well as by aging, two periods of life during which microglial activity is known to be specifically upregulated. Lasting changes in (the ratios of) specific microglial phenotypes can result in an exaggerated pro inflammatory cytokine response to subsequent inflammatory challenges. While the resulting changes in brain function are initially transient, a continued and/or excess release of such pro-inflammatory cytokines can activate various downstream cellular cascades known to be relevant for AD. Finally, we discuss microglial priming and the aberrant microglial response as potential target for treatment strategies for AD. PMID- 27555815 TI - A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome. AB - Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)-microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker "retinoic acid" in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5'-AGGTCA-3') in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it. PMID- 27555816 TI - Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks. AB - Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross correlations) influence the efficacy variability under pair-wise additive spike timing dependent plasticity (STDP) and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded), by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF) neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy). PMID- 27555817 TI - Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences. AB - Chronic tendinopathy is a painful common condition affecting athletes as well as the general population undergoing to tendon overuse. Although its huge prevalence, little is known about tendinopathy pathogenesis, and even cloudier is its treatment. Traditionally, tendinopathy has been defined as a lack of tendon ability to overcome stressing stimuli with appropriate adaptive changes. Histologic studies have demonstrated the absence of inflammatory infiltrates, as a consequence conventional antinflammatory drugs have shown little or no effectiveness in treating tendinopathies. New strategies should be therefore identified to address chronic tendon disorders. Angiofibroblastic changes have been highlighted as the main feature of tendinopathy, and vascular endothelial growth factor (VEGF) has been demonstrated as one of the key molecules involved in vascular hyperplasia. More recently, attention has been focused on new peptides such as Substance P, nitric oxide, and calcitonin gene-related peptide (CGRP). Those new findings support the idea of a nerve-mediated disregulation of tendon metabolism. Each of those molecules could be a target for new treatment options. This study aimed to systematically review the current available clinical and basic science in order to summarize the latest evidences on the pathophysiology and its effect on treatment of chronic tendinopathy, and to spread suggestions for future research on its treatment. PMID- 27555819 TI - Association between hs-CRP Levels and the Outcomes of Patients with Small-Artery Occlusion. AB - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is not only a marker of inflammation but also a prognostic factor for ischemic stroke. The objective of our study was to investigative the association between hs-CRP levels and outcomes of patients with small-artery occlusion (SAO). METHODS: We selected 718 participants diagnosed with SAO (according to Trial of Org 10172 in Acute Stroke Treatment classification) using the stroke registry of the Department of Neurorehabilitation of Tianjin HuanHu Hospital. Hs-CRP values at admission were classified into 3 categories: <0.91 mg/L, 0.91 to <2.77 mg/L, and >=2.77 mg/L. Patients were divided into two subgroups based on age: the younger subgroup (<75years) and the elder subgroup (>=75 years). Clinical outcomes were evaluated with the modified Rankin scale (mRS) 3 months after the onset of stroke. We examined the relationship between hs-CRP levels at the time of admission and mRS scores using multivariate logistic regression analysis. We also assessed the association between hs-CRP levels and patient outcomes according to age. RESULTS: Among 718 patients with SAO (mean age, 61.7 +/- 11.3 years), median hs-CRP was 1.54 mg/L. Although 628 patients had a favorable outcome, and 90 patients had a poor outcome at 3 months after SAO. Compared with the lowest levels of hs-CRP, those highest levels of hs-CRP (hs-CRP > 2.77 mg/L) were at increased risk of poor outcome (adjusted odds ratio, 1.917; 95% CI, 1.050-3.500; P = 0.034), and more than twice the risk of poor outcome among patients in the younger subgroup (adjusted odds ratio, 2.092; 95% CI, 1.079-4.058; P = 0.029). These associations persisted after adjustment for confounding risk factors. However, hs-CRP levels were not significantly associated with outcome among patients in the elder subgroup. CONCLUSIONS: Elevated hs-CRP in patients with SAO is an independent predictor of poor prognosis; however, this association is only present in younger patients (<75 years). PMID- 27555818 TI - Lifespan Changes in the Countermanding Performance of Young and Middle Aged Adult Rats. AB - Inhibitory control can be investigated with the countermanding task, which requires subjects to make a response to a go signal and cancel that response when a stop signal is presented occasionally. Adult humans performing the countermanding task typically exhibit impaired response time (RT), stop signal response time (SSRT) and response accuracy as they get older, but little change in post-error slowing. Rodent models of the countermanding paradigm have been developed recently, yet none have directly examined age-related changes in performance throughout the lifespan. Male Wistar rats (N = 16) were trained to respond to a visual stimulus (go signal) by pressing a lever directly below an illuminated light for food reward, but to countermand the lever press subsequent to a tone (stop signal) that was presented occasionally (25% of trials) at a variable delay. Subjects were tested in 1 h sessions at approximately 7 and 12 months of age with intermittent training in between. Rats demonstrated longer go trial RT, a higher proportion of go trial errors and performed less total trials at 12, compared to 7 months of age. Consistent SSRT and post-error slowing were observed for rats at both ages. These results suggest that the countermanding performance of rats does vary throughout the lifespan, in a manner similar to humans, suggesting that rodents may provide a suitable model for behavioral impairment related to normal aging. These findings also highlight the importance of indicating the age at which rodents are tested in countermanding investigations. PMID- 27555820 TI - Inhibition of P-Glycoprotein and Multidrug Resistance-Associated Protein 2 Regulates the Hepatobiliary Excretion and Plasma Exposure of Thienorphine and Its Glucuronide Conjugate. AB - Thienorphine (TNP) is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G) undergo significant bile excretion. The purpose of this study was to investigate the roles of efflux transporters in regulating biliary excretion and plasma exposure of TNP and TNP-G. An ATPase assay suggested that TNP and TNP-G were substrates of P-gp and MRP2, respectively. The in vitro data from rat hepatocytes showed that bile excretion of TNP and TNP-G was regulated by the P-gp and MRP2 modulators. The accumulation of TNP and TNP-G in HepG2 cells significantly increased by the treatment of mdr1a or MRP2 siRNA for P-gp or MRP2 modulation. In intact rats, the bile excretion, and pharmacokinetic profiles of TNP and TNP-G were remarkably changed with tariquidar and probenecid pretreatment, respectively. Tariquidar increased the Cmax and AUC0-t and decreased MRT and T1/2 of TNP, whereas probenecid decreased the plasma exposure of TNP-G and increased its T1/2. Knockdown P-gp and MRP2 function using siRNA significantly increased the plasma exposure of TNP and TNP-G and reduced their mean retention time in mice. These results indicated the important roles of P-gp and MRP2 in hepatobiliary excretion and plasma exposure of TNP and TNP-G. Inhibition of the efflux transporters may affect the pharmacokinetics of TNP and result in a drug-drug interaction between TNP and the concomitant transporter inhibitor or inducer in clinic. PMID- 27555821 TI - Pharmacist Remote Review of Medication Prescriptions for Appropriateness in Pediatric Intensive Care Unit. AB - BACKGROUND: One aspect of ordering and prescribing medication is the requirement for a trained professional to review medication orders or prescriptions for appropriateness. In practice, this review process is usually performed by a clinical pharmacist. However, in many medical centers there is a shortage of staff and a pharmacist is not always available. OBJECTIVE: To determine whether remote review of medication orders by a pharmacist is a plausible method in a pediatric intensive care unit (PICU). METHODS: A pharmacist from the pharmacy department reviewed medication orders of patients admitted to our PICU over a 7 month period for appropriateness. A special form for medical orders was filled in and sent to the physician in the PICU, who replied informing whether the recommendation had been accepted. The time spent by the pharmacist for this activity was recorded. RESULTS: The review time for one medical record was 8.9 (95% CI, 6.9-10.9) min. Every additional drug prescribed increased the total review time by 0.8 (95% CI, 0.45-1.11) min. The pharmacist filled in 186 forms on 117 admissions for 109 children. The median review time was 15 (12.8-18.8) and 12 (9-15) min, respectively, for patients with psychiatric-neurologic disorders compared to those without (p = 0.032). Usually, a daily workload of 240 min was needed for the pharmacist accompanying the round in contrast to 108 min per day needed to review all the medical records in 95% of the cases. The physician accepted 51.2%, rejected 11.9%, and made no comment on 36.9% of the recommendations. CONCLUSION: Hospitals facing budget shortages can carry out focused remote reviews of prescriptions by the pharmacist. PMID- 27555822 TI - Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats. AB - Lignosus also known as "Tiger Milk Mushroom," is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg. PMID- 27555823 TI - Comparative Multifractal Analysis of Dynamic Infrared Thermograms and X-Ray Mammograms Enlightens Changes in the Environment of Malignant Tumors. AB - There is growing evidence that the microenvironment surrounding a tumor plays a special role in cancer development and cancer therapeutic resistance. Tumors arise from the dysregulation and alteration of both the malignant cells and their environment. By providing tumor-repressing signals, the microenvironment can impose and sustain normal tissue architecture. Once tissue homeostasis is lost, the altered microenvironment can create a niche favoring the tumorigenic transformation process. A major challenge in early breast cancer diagnosis is thus to show that these physiological and architectural alterations can be detected with currently used screening techniques. In a recent study, we used a 1D wavelet-based multi-scale method to analyze breast skin temperature temporal fluctuations collected with an IR thermography camera in patients with breast cancer. This study reveals that the multifractal complexity of temperature fluctuations superimposed on cardiogenic and vasomotor perfusion oscillations observed in healthy breasts is lost in malignant tumor foci in cancerous breasts. Here we use a 2D wavelet-based multifractal method to analyze the spatial fluctuations of breast density in the X-ray mammograms of the same panel of patients. As compared to the long-range correlations and anti-correlations in roughness fluctuations, respectively observed in dense and fatty breast areas, some significant change in the nature of breast density fluctuations with some clear loss of correlations is detected in the neighborhood of malignant tumors. This attests to some architectural disorganization that may deeply affect heat transfer and related thermomechanics in breast tissues, corroborating the change to homogeneous monofractal temperature fluctuations recorded in cancerous breasts with the IR camera. These results open new perspectives in computer-aided methods to assist in early breast cancer diagnosis. PMID- 27555824 TI - Prosocial Personality Traits Differentially Predict Egalitarianism, Generosity, and Reciprocity in Economic Games. AB - Recent research has highlighted the role of prosocial personality traits agreeableness and honesty-humility-in egalitarian distributions of wealth in the dictator game. Expanding on these findings, we ran two studies to examine individual differences in two other forms of prosociality-generosity and reciprocity-with respect to two major models of personality, the Big Five and the HEXACO. Participants (combined N = 560) completed a series of economic games in which allocations in the dictator game were compared with those in the generosity game, a non-constant-sum wealth distribution task where proposers with fixed payoffs selected the size of their partner's payoff ("generosity"). We further examined positive and negative reciprocity by manipulating a partner's previous move ("reciprocity"). Results showed clear evidence of both generosity and positive reciprocity in social preferences, with allocations to a partner greater in the generosity game than in the dictator game, and greater still when a player had been previously assisted by their partner. There was also a consistent interaction with gender, whereby men were more generous when this was costless and women were more egalitarian overall. Furthermore, these distinct forms of prosociality were differentially predicted by personality traits, in line with the core features of these traits and the theoretical distinctions between them. HEXACO honesty-humility predicted dictator, but not generosity allocations, while traits capturing tendencies toward irritability and anger predicted lower generosity, but not dictator allocations. In contrast, the politeness-but not compassion-aspect of Big Five agreeableness was uniquely and broadly associated with prosociality across all games. These findings support the discriminant validity between related prosocial constructs, and have important implications for understanding the motives and mechanisms taking place within economic games. PMID- 27555825 TI - "The Bitter Laughter". When Parody Is a Moral and Affective Priming in Political Persuasion. AB - Research on socially aware systems requires fine-grained knowledge of the mechanisms of persuasion in order to promote civic knowledge and aware political participation. Within humor studies, political parody is generally considered a simple pleasant weapon for political evaluation, currently explained by referring to the so called "just a joke effect" (Nabi et al., 2007). Indeed the funny side of parody can induce positive emotions, but it also includes a discrediting act that sometimes produces a "bitter laughter." The present study aims to understand the role played by negative and moral emotions aroused by parody. A parody is defined as a communicative behavior (a discourse, text, body movement, song) that imitates a communicative behavior or trait displayed by some Target by reproducing it in a distorted way, with the aim of making fun of the Target. Based on a socio-cognitive approach, a distinction is made between "surface" and "deep" parody (Poggi and D'Errico, 2013), with the former simply imitating behaviors actually displayed by the Target, and the latter implying a (humorous) re-categorization of the Target. The paper studies the effect of these two different types of parody on persuasion processes. Results show that the deep parody, as opposed to surface parody, triggers more negative emotions, and in particular indignation, that in turn lead to more negative evaluations of the Target. Moreover, the moral priming of parody is influenced by the Target politician's gender. PMID- 27555826 TI - The Effects of Auditory Contrast Tuning upon Speech Intelligibility. AB - We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure. PMID- 27555827 TI - Effects of Emotional Experience in Lexical Decision. AB - Previous research has examined the effects of emotional experience (i.e., the ease with which words evoke emotion information) in semantic categorization (SCT), word naming, and Stroop tasks (Newcombe et al., 2012; Siakaluk et al., 2014; Moffat et al., 2015). However, to date there are no published reports on whether emotional experience influences performance in the lexical decision task (LDT). In the present study, we examined the influence of emotional experience in LDT using three different stimulus sets. In Experiment 1 we used a stimulus set used by both Kousta et al. (2009; Experiment 1) and Yap and Seow (2014) that is comprised of 40 negative, 40 positive, and 40 neutral words; in Experiment 2 we used a stimulus set comprised of 150 abstract nouns; and in Experiment 3 we used a stimulus set comprised of 373 verbs. We observed facilitatory effects of emotional experience in each of the three experiments, such that words with higher emotional experience ratings were associated with faster response latencies. These results are important because the influence of emotional experience: (a) is observed in stimulus sets comprised of different types of words, demonstrating the generalizability of the effect in LDT; (b) accounts for LDT response latency variability above and beyond the influences of valence and arousal, and is thus a robust dimension of conceptual knowledge; PMID- 27555828 TI - A Comparative Analysis of the Universal Elements of Music and the Fetal Environment. AB - Although the idea that pulse in music may be related to human pulse is ancient and has recently been promoted by researchers (Parncutt, 2006; Snowdon and Teie, 2010), there has been no ordered delineation of the characteristics of music that are based on the sounds of the womb. I describe features of music that are based on sounds that are present in the womb: tempo of pulse (pulse is understood as the regular, underlying beat that defines the meter), amplitude contour of pulse, meter, musical notes, melodic frequency range, continuity, syllabic contour, melodic rhythm, melodic accents, phrase length, and phrase contour. There are a number of features of prenatal development that allow for the formation of long term memories of the sounds of the womb in the areas of the brain that are responsible for emotions. Taken together, these features and the similarities between the sounds of the womb and the elemental building blocks of music allow for a postulation that the fetal acoustic environment may provide the bases for the fundamental musical elements that are found in the music of all cultures. This hypothesis is supported by a one-to-one matching of the universal features of music with the sounds of the womb: (1) all of the regularly heard sounds that are present in the fetal environment are represented in the music of every culture, and (2) all of the features of music that are present in the music of all cultures can be traced to the fetal environment. PMID- 27555829 TI - The Personality Trait of Intolerance to Uncertainty Affects Behavior in a Novel Computer-Based Conditioned Place Preference Task. AB - Recent work has found that personality factors that confer vulnerability to addiction can also affect learning and economic decision making. One personality trait which has been implicated in vulnerability to addiction is intolerance to uncertainty (IU), i.e., a preference for familiar over unknown (possibly better) options. In animals, the motivation to obtain drugs is often assessed through conditioned place preference (CPP), which compares preference for contexts where drug reward was previously received. It is an open question whether participants with high IU also show heightened preference for previously rewarded contexts. To address this question, we developed a novel computer-based CPP task for humans in which participants guide an avatar through a paradigm in which one room contains frequent reward (i.e., rich) and one contains less frequent reward (i.e., poor). Following exposure to both contexts, subjects are assessed for preference to enter the previously rich and previously poor room. Individuals with low IU showed little bias to enter the previously rich room first, and instead entered both rooms at about the same rate which may indicate a foraging behavior. By contrast, those with high IU showed a strong bias to enter the previously rich room first. This suggests an increased tendency to chase reward in the intolerant group, consistent with previously observed behavior in opioid-addicted individuals. Thus, the personality factor of high IU may produce a pre-existing cognitive bias that provides a mechanism to promote decision-making processes that increase vulnerability to addiction. PMID- 27555830 TI - Large Group Exposure Treatment: a Feasibility Study in Highly Spider Fearful Individuals. AB - A large group one-session exposure treatment (LG-OST) based on indirect modeled exposure strategies was carried out to investigate its feasibility and effectiveness in a sample of highly spider fearful individuals (N = 78). The stability of LG-OST-effects was assessed at 8-month follow-up (FU). Furthermore, a second sample (N = 30) of highly spider fearful individuals was treated in a standard, single-person one-session treatment (SP-OST) design to compare LG-OST effects to a standard spider fear treatment. Participants' fear of spider was assessed by multiple questionnaires and by a behavioral approach test. The fear assessment took place before and after the respective intervention, and at 8 month FU in LG-OST. Regarding subjective spider fear measures, LG-OST mainly showed medium to large effect sizes, ranging from Cohen's d = 0.69 to d = 1.21, except for one small effect of d = 0.25. After LG-OST, participants approached the spider closer at post-treatment measures (d = 1.18). LG-OST-effects remained stable during the 8-month FU-interval. However, SP-OST-effects proved superior in most measures. An LG-OST-protocol provided evidence for feasibility and efficiency. The effects of LG-OST were equal to those of indirect modeled exposure strategies, carried out in single-settings. LG-OST may represent a useful tool in future phobia-treatment, especially if it can match the effects of single-setting OST, e.g., by including more direct exposure elements in future large group attempts. PMID- 27555831 TI - Down with Retirement: Implications of Embodied Cognition for Healthy Aging. AB - Cognitive and neurocognitive approaches to human healthy aging attribute age related decline to the biologically caused loss of cognitive-control functions. However, an embodied-cognition approach to aging implies a more interactive view according to which cognitive control emerges from, and relies on a person's active encounters with his or her physical and social environment. We argue that the availability of cognitive-control resources does not only rely on biological processes but also on the degree of active maintenance, that is, on the systematic use of the available control resources. Unfortunately, there is evidence that the degree of actual use might systematically underestimate resource availability, which implies that elderly individuals do not fully exploit their cognitive potential. We discuss evidence for this possibility from three aging-related issues: the reduction of dopaminergic supply, loneliness, and the loss of body strength. All three phenomena point to a downward spiral, in which losses of cognitive-control resources do not only directly impair performance but also more indirectly discourage individuals from making use of them, which in turn suggests underuse and a lack of maintenance-leading to further loss. On the positive side, the possibility of underuse points to not yet fully exploited reservoirs of cognitive control, which calls for more systematic theorizing and experimentation on how cognitive control can be enhanced, as well as for reconsiderations of societal practices that are likely to undermine the active maintenance of control resources-such as retirement laws. PMID- 27555832 TI - Exploring the Link among State of Mind Concerning Childhood Attachment, Attachment in Close Relationships, Parental Bonding, and Psychopathological Symptoms in Substance Users. AB - BACKGROUND: In the present study, we have explored the link among styles of attachment and psychopathology in drug users. We know that insecure attachment predisposes the individuals the development of drug-addiction and psychopathological symptoms. However, we do not know which attachment is more frequent in drug users and which is related to particular psychopathological symptoms. The aim of the present work is to explore the relationship between childhood attachment state of mind, attachment in close relationships, parental bonding and psychopathology in sample of Italian substance users. METHODS: We explored, in a sample of 70 drug users and drug-addicted patients, the childhood attachment state of mind measured by the Adult Attachment Interview, the attachment in close relationships by the Relationship Questionnaire and parental bonding measured by the Parental Bonding Instrument. The Symptom Check-List-90-R (SCL-90-R) measured psychopathological symptoms. RESULTS: We found that parental bonding, rather than state of mind concerning childhood attachment or attachment in close relationships, is related to the psychopathological manifestation of anxiety, hostility, depression, and paranoid ideation in the sample. The latter occurs frequently in our sample, independent of state of mind concerning child attachment, attachment in close relationships, and parental bonding, suggesting its role either as a factor that favors a bad image of the participants' own relationships or as a direct effect of consuming drugs. CONCLUSION: These results have clinical implications on suggesting ways of interventions that prevent drug addiction, which should include the evaluation of attachment in the prodromic phases of substance use onset or rehabilitation programs to prevent and manage psychotic-like symptoms. PMID- 27555833 TI - Approaching the Distinction between Intuition and Insight. AB - Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight. PMID- 27555834 TI - Distracted While Reading? Changing to a Hard-to-Read Font Shields against the Effects of Environmental Noise and Speech on Text Memory. AB - The purpose of this study was to investigate the distractive effects of background speech, aircraft noise and road traffic noise on text memory and particularly to examine if displaying the texts in a hard-to-read font can shield against the detrimental effects of these types of background sounds. This issue was addressed in an experiment where 56 students read shorter texts about different classes of fictitious creatures (i.e., animals, fishes, birds, and dinosaurs) against a background of the aforementioned background sounds respectively and silence. For half of the participants the texts were displayed in an easy-to-read font (i.e., Times New Roman) and for the other half in a hard to-read font (i.e., Haettenschweiler). The dependent measure was the proportion correct answers on the multiple-choice tests that followed each sound condition. Participants' performance in the easy-to-read font condition was significantly impaired by all three background sound conditions compared to silence. In contrast, there were no effects of the three background sound conditions compared to silence in the hard-to-read font condition. These results suggest that an increase in task demand-by displaying the text in a hard-to-read font-shields against various types of distracting background sounds by promoting a more steadfast locus-of-attention and by reducing the processing of background sound. PMID- 27555835 TI - Subjectivity: A Case of Biological Individuation and an Adaptive Response to Informational Overflow. AB - The article presents a perspective on the scientific explanation of the subjectivity of conscious experience. It proposes plausible answers for two empirically valid questions: the 'how' question concerning the developmental mechanisms of subjectivity, and the 'why' question concerning its function. Biological individuation, which is acquired in several different stages, serves as a provisional description of how subjective perspectives may have evolved. To the extent that an individuated informational space seems the most efficient way for a given organism to select biologically valuable information, subjectivity is deemed to constitute an adaptive response to informational overflow. One of the possible consequences of this view is that subjectivity might be (at least functionally) dissociated from consciousness, insofar as the former primarily facilitates selection, the latter action. PMID- 27555836 TI - Production of Thermostable Organic Solvent Tolerant Keratinolytic Protease from Thermoactinomyces sp. RM4: IAA Production and Plant Growth Promotion. AB - There are several reports about the optimization of protease production, but only few have optimized the production of organic solvent tolerant keratinolytic proteases that show remarkable exploitation in the development of the non polluting processes in biotechnological industries. The present study was carried with aim to optimize the production of a thermostable organic solvent tolerant keratinolytic protease Thermoactinomyces sp. RM4 utilizing chicken feathers. Thermoactinomyces sp. RM4 isolated from the soil sample collected from a rice mill wasteyard site near Kashipur, Uttrakhand was identified on the basis of 16S rDNA analysis. The production of organic solvent tolerant keratinolytic protease enzyme by Thermoactinomyces sp. RM4 was optimized by varying physical culture conditions such as pH (10.0), temperature (60 degrees C), inoculum percentage (2%), feather concentration (2%) and agitation rate (2 g) for feather degradation. The result showed that Thermoactinomyces sp. RM4 potentially produces extra-cellular thermostable organic solvent tolerant keratinolytic protease in the culture medium. Further, the feather hydrolysate from keratinase production media showed plant growth promoting activity by producing indole-3 acetic acid itself. The present findings suggest that keratinolytic protease from Thermoactinomyces sp. RM4 offers enormous industrial applications due to its organic solvent tolerant property in peptide synthesis, practical role in feather degradation and potential function in plant growth promoting activity, which might be a superior candidate to keep ecosystem healthy and functional. PMID- 27555837 TI - A Bayesian Framework for the Classification of Microbial Gene Activity States. AB - Numerous methods for classifying gene activity states based on gene expression data have been proposed for use in downstream applications, such as incorporating transcriptomics data into metabolic models in order to improve resulting flux predictions. These methods often attempt to classify gene activity for each gene in each experimental condition as belonging to one of two states: active (the gene product is part of an active cellular mechanism) or inactive (the cellular mechanism is not active). These existing methods of classifying gene activity states suffer from multiple limitations, including enforcing unrealistic constraints on the overall proportions of active and inactive genes, failing to leverage a priori knowledge of gene co-regulation, failing to account for differences between genes, and failing to provide statistically meaningful confidence estimates. We propose a flexible Bayesian approach to classifying gene activity states based on a Gaussian mixture model. The model integrates genome wide transcriptomics data from multiple conditions and information about gene co regulation to provide activity state confidence estimates for each gene in each condition. We compare the performance of our novel method to existing methods on both simulated data and real data from 907 E. coli gene expression arrays, as well as a comparison with experimentally measured flux values in 29 conditions, demonstrating that our method provides more consistent and accurate results than existing methods across a variety of metrics. PMID- 27555838 TI - Endogenous Retroviruses in Fish Genomes: From Relics of Past Infections to Evolutionary Innovations? AB - The increasing availability of fish genome sequences has allowed to gain new insights into the diversity and host distribution of retroviruses in fish and other vertebrates. This distribution can be assessed through the identification and analysis of endogenous retroviruses, which are proviral remnants of past infections integrated in genomes. Retroviral sequences are probably important for evolution through their ability to induce rearrangements and to contribute regulatory and coding sequences; they may also protect their host against new infections. We argue that the current mass of genome sequences will soon strongly improve our understanding of retrovirus diversity and evolution in aquatic animals, with the identification of new/re-emerging elements and host resistance genes that restrict their infectivity. PMID- 27555839 TI - Soil Fungal:Bacterial Ratios Are Linked to Altered Carbon Cycling. AB - Despite several lines of observational evidence, there is a lack of consensus on whether higher fungal:bacterial (F:B) ratios directly cause higher soil carbon (C) storage. We employed RNA sequencing, protein profiling and isotope tracer techniques to evaluate whether differing F:B ratios are associated with differences in C storage. A mesocosm (13)C labeled foliar litter decomposition experiment was performed in two soils that were similar in their physico-chemical properties but differed in microbial community structure, specifically their F:B ratio (determined by PLFA analyses, RNA sequencing and protein profiling; all three corroborating each other). Following litter addition, we observed a consistent increase in abundance of fungal phyla; and greater increases in the fungal dominated soil; implicating the role of fungi in litter decomposition. Litter derived (13)C in respired CO2 was consistently lower, and residual (13)C in bulk SOM was higher in high F:B soil demonstrating greater C storage potential in the F:B dominated soil. We conclude that in this soil system, the increased abundance of fungi in both soils and the altered C cycling patterns in the F:B dominated soils highlight the significant role of fungi in litter decomposition and indicate that F:B ratios are linked to higher C storage potential. PMID- 27555840 TI - Actin and DNA Protect Histones from Degradation by Bacterial Proteases but Inhibit Their Antimicrobial Activity. AB - Histones are small polycationic proteins located in the cell nucleus. Together, DNA and histones are integral constituents of the nucleosomes. Upon apoptosis, necrosis, and infection - induced cell death, histones are released from the cell. The extracellular histones have strong antimicrobial activity but are also cytotoxic and thought as mediators of cell death in sepsis. The antimicrobial activity of the cationic extracellular histones is inhibited by the polyanionic DNA and F-actin, which also become extracellular upon cell death. DNA and F-actin protect histones from degradation by the proteases of Pseudomonas aeruginosa and Porphyromonas gingivalis. However, though the integrity of the histones is protected, the activity of histones as antibacterial agents is lost. The inhibition of the histone's antibacterial activity and their protection from proteolysis by DNA and F-actin indicate a tight electrostatic interaction between the positively charged histones and negatively charged DNA and F-actin, which may have physiological significance in maintaining the equilibrium between the beneficial antimicrobial activity of extracellular histones and their cytotoxic effects. PMID- 27555841 TI - Phenotypic and Genetic Heterogeneity in Vibrio cholerae O139 Isolated from Cholera Cases in Delhi, India during 2001-2006. AB - Incidence of epidemic Vibrio cholerae serogroup O139 has declined in cholera endemic countries. However, sporadic cholera caused by V. cholerae O139 with notable genetic changes is still reported from many regions. In the present study, 42 V. cholerae O139 strains isolated from 2001 to 2006 in Delhi, India, were retrospectively analyzed to understand their phenotype and molecular characteristics. The majority of isolates were resistant to ampicillin, furazolidone and nalidixic acid. Though the integrative conjugative element was detected in all the O139 isolates, the 2004-2006 isolates remained susceptible to co-trimoxazole, chloramphenicol, and streptomycin. Cholera toxin genotype 1 was present in the majority of the O139 isolates while few had type 3 or a novel type 4. In the cholera toxin encoding gene (ctx) restriction fragment length polymorphism, the majority of the isolates harbored three copies of CTX element, of which one was truncated. In this study, the ctx was detected for the first time in the small chromosome of V. cholerae O139 and one isolate harbored 5 copies of CTX element, of which 3 were truncated. The ribotype BII pattern was found in most of the O139 isolates. Three V. cholerae O139 isolated in 2001 had a new ribotype BVIII. Pulsed-field gel electrophoresis analysis revealed clonal variation in 2001 isolates compared to the 2004-2006 isolates. Molecular changes in V. cholerae O139 have to be closely monitored as this information may help in understanding the changing genetic features of this pathogen in relation to the epidemiology of cholera. PMID- 27555842 TI - Prophylactic Bacteriophage Administration More Effective than Post-infection Administration in Reducing Salmonella enterica serovar Enteritidis Shedding in Quail. AB - Infections caused by Salmonella bacteria, often through poultry products, are a serious public health issue. Because of drawbacks associated with antibiotic prophylaxis, alternative treatments are sought. Bacterial viruses (bacteriophages) may provide an effective alternative, but concerns remain with respect to bacteriophage stability and effectiveness. To this end, we assessed the stability of a novel bacteriophage isolated from poultry excreta, siphovirus PSE, and its effectiveness in reducing Salmonella enterica serovar Enteritidis colonization in vitro and in vivo. Moreover, we sought to determine how the timing (prophylactic or therapeutic) and route (oral gavage or vent lip) of PSE administration impacted its effectiveness. Here we report that significant quantities of viable PSE bacteriophages were recovered following exposure to high and low pH, high temperatures, and bile salts, testifying to its ability to survive extreme conditions. In addition, we found that ileal lactic acid bacteria and Streptococcus spp. counts increased, but colibacilli and total aerobe counts decreased, in quail receiving phage PSE through both oral gavage and vent lip routes. In other experiments, we assessed the efficiency of PSE administration, in both prophylactic and therapeutic contexts, via either oral gavage or vent lip administration, on S. Enteritidis colonization of quail cecal tonsils. Our results demonstrate that administration of PSE as a preventive agent could reduce the S. Enteritidis colonization more effectively than post-challenge administration. Furthermore, oral administration of PSE phage is a more effective prophylactic tool for reduction of S. Enteritidis shedding in poultry than is vent lip administration. PMID- 27555843 TI - Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy. AB - It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 MUM concentrations, whereas in in vivo the growth delay was limited with 24-48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID- 27555844 TI - A Flow Cytometric and Computational Approaches to Carbapenems Affinity to the Different Types of Carbapenemases. AB - The synergy of carbapenem combinations regarding Enterobacteriaceae producing different types of carbapenemases was study through different approaches: flow cytometry and computational analysis. Ten well characterized Enterobacteriaceae (KPC, verona integron-encoded metallo-beta-lactamases -VIM and OXA-48-like enzymes) were selected for the study. The cells were incubated with a combination of ertapenem with imipenem, meropenem, or doripenem and killing kinetic curves performed with and without reinforcements of the drugs. A cephalosporin was also used in combination with ertapenem. A flow cytometric assay with DiBAC4-(3), a membrane potential dye, was developed in order to evaluate the cellular lesion after 2 h incubation. A chemical computational study was performed to understand the affinity of the different drugs to the different types of enzymes. Flow cytometric analysis and time-kill assays showed a synergic effect against KPC and OXA-48 producing-bacteria with all combinations; only ertapenem with imipenem was synergic against VIM producing-bacteria. A bactericidal effect was observed in OXA-48-like enzymes. Ceftazidime plus ertapenem was synergic against ESBL negative KPC producing-bacteria. Ertapenem had the highest affinity for those enzymes according to chemical computational study. The synergic effect between ertapenem and others carbapenems against different carbapenemase-producing bacteria, representing a therapeutic choice, was described for the first time. Easier and faster laboratorial methods for carbapenemase characterization are urgently needed. The design of an ertapenem derivative with similar affinity to carbapenemases but exhibiting more stable bonds was demonstrated as highly desirable. PMID- 27555845 TI - Biosynthesis and Functional Significance of Peripheral Node Addressin in Cancer Associated TLO. AB - Peripheral node addressin (PNAd) marks high endothelial venules (HEV), which are crucial for the recruitment of lymphocytes into lymphoid organs in non-mucosal tissue sites. PNAd is a sulfated and fucosylated glycoprotein recognized by the prototypic monoclonal antibody, MECA-79. PNAd is the ligand for L-selectin, which is expressed on the surface of naive and central memory T cells, where it mediates leukocyte rolling on vascular endothelial surfaces. Although PNAd was first identified in the HEV of peripheral lymph nodes, recent work suggests a critical role for PNAd in the context of chronic inflammatory diseases, where it can be used as a marker for the formation of tertiary lymphoid organs (TLOs). TLO form in tissues impacted by sustained inflammation, such as the tumor microenvironment where they function as local sites of adaptive immune cell priming. This allows for specific B- and T-cell responses to be initiated or reactivated in inflamed tissues without dependency on secondary lymphoid organs. Recent studies of cancer in mice and humans have identified PNAd as a biomarker of improved disease prognosis. Blockade of PNAd or its ligand, L-selectin, can abrogate protective antitumor immunity in murine models. This review examines pathways regulating PNAd biosynthesis by the endothelial cells integral to HEV and the formation and maintenance of lymphoid structures throughout the body, particularly in the setting of cancer. PMID- 27555847 TI - Roostocks/Scion/Nitrogen Interactions Affect Secondary Metabolism in the Grape Berry. AB - The present work investigates the interactions between soil content, rootstock, and scion by focusing on the effects of roostocks and nitrogen supply on grape berry content. Scions of Cabernet Sauvignon (CS) and Pinot Noir (PN) varieties were grafted either on Riparia Gloire de Montpellier (RGM) or 110 Richter (110R) rootstock. The 4 rooststock/scion combinations were fertilized with 3 different levels of nitrogen after fruit set. Both in 2013 and 2014, N supply increased N uptake by the plants, and N content both in vegetative and reproductory organs. Rootstock, variety and year affected berry weight at harvest, while nitrogen did not affect significantly this parameter. Grafting on RGM consistently increased berry weight compared to 110R. PN consistently produced bigger berries than CS. CS berries were heavier in 2014 than in 2013, but the year effect was less marked for PN berries. The berries were collected between veraison and maturity, separated in skin and pulp, and their content was analyzed by conventional analytical procedures and untargeted metabolomics. For anthocyanins, the relative quantitation was fairly comparable with both LC-MS determination and HPLC-DAD, which is a fully quantitative technique. The data show complex responses of the metabolite content (sugars, organic acids, amino acids, anthocyanins, flavonols, flavan-3-ols/procyanidins, stilbenes, hydroxycinnamic, and hydroxybenzoic acids) that depend on the rootstock, the scion, the vintage, the nitrogen level, the berry compartment. This opens a wide range of possibilities to adjust the content of these compounds through the choice of the roostock, variety and nitrogen fertilization. PMID- 27555846 TI - Modulation of Alloimmunity by Heat Shock Proteins. AB - The immunological mechanisms that evolved for host defense against pathogens and injury are also responsible for transplant rejection. Host rejection of foreign tissue was originally thought to be mediated mainly by T cell recognition of foreign MHC alleles. Management of solid organ transplant rejection has thus focused mainly on inhibition of T cell function and matching MHC alleles between donor and host. Recently, however, it has been demonstrated that the magnitude of the initial innate immune responses upon transplantation has a decisive impact on rejection. The exact mechanisms underlying this phenomenon have yet to be characterized. Ischemic cell death and inflammation that occur upon transplantation are synonymous with extracellular release of various heat shock proteins (Hsps), many of which have been shown to have immune-modulatory properties. Here, we review the impact of Hsps upon alloimmunity and discuss the potential use of Hsps as accessory agents to improve solid organ transplant outcomes. PMID- 27555848 TI - Environmental pH and the Requirement for the Extrinsic Proteins of Photosystem II in the Function of Cyanobacterial Photosynthesis. AB - In one of the final stages of cyanobacterial Photosystem II (PS II) assembly, binding of up to four extrinsic proteins to PS II stabilizes the oxygen-evolving complex (OEC). Growth of cyanobacterial mutants deficient in certain combinations of these thylakoid-lumen-associated polypeptides is sensitive to changes in environmental pH, despite the physical separation of the membrane-embedded PS II complex from the external environment. In this perspective we discuss the effect of environmental pH on OEC function and photoautotrophic growth in cyanobacteria with reference to pH-sensitive PS II mutants lacking extrinsic proteins. We consider the possibilities that, compared to pH 10.0, pH 7.5 increases susceptibility to PS II-generated reactive oxygen species (ROS) causing photoinhibition and reducing PS II assembly in some mutants, and that perturbations to channels in the lumenal regions of PS II might alter the accessibility of water to the active site as well as egress of oxygen and protons to the thylakoid lumen. Reduced levels of PS II in these mutants, and reduced OEC activity arising from the disruption of substrate/product channels, could reduce the trans-thylakoid pH gradient (DeltapH), leading to the impairment of photosynthesis. Growth of some PS II mutants at pH 7.5 can be rescued by elevating CO2 levels, suggesting that the pH-sensitive phenotype might primarily be an indirect result of back-pressure in the electron transport chain that results in heightened production of ROS by the impaired photosystem. PMID- 27555849 TI - Cocowood Fibrovascular Tissue System-Another Wonder of Plant Evolution. AB - The coconut palm (Cocos nucifera L.) stem tissue (referred to as cocowood in this study) is a complex fibrovascular system that is made up of fibrovascular bundles embedded into a parenchymatous ground tissue. The complex configuration of fibrovascular bundles along with the non-uniform distribution of the material properties likely allow senile coconut stems to optimize their biomechanical performance per unit mass (i.e., mechanical efficiency) and grow into tall, slender, and very flexible plants with minimum resources of biomass and water. For the first time, to the best of the authors' knowledge, this paper examines, from the integral (i.e., stem structure) and macroscopic (i.e., tissue structure) levels of hierarchy, the characteristic triple helix formation depicted by the fibrovascular bundles within the monocotyledon cocowood. The natural course of the tangential orientation of the axial fibrovascular bundles is mapped for the whole cocowood structure by quantifying 264 cocowood discs, corresponding to 41 senile coconut palms estimated to be >70 years old. The observed variations were modeled in this paper by simple equations that partially enabled characterization of the cocowood fibrovascular tissue system. Furthermore, 11 finite element analyses (FEA) were performed over a three dimensional (3D) finite element (FE) model resembling a characteristic coconut palm stem of 25 m in height to analyze the biomaterial reactions produced by the progressive deviation of the tangential fibrovascular bundles on the cocowood mechanical response (i.e., on the material compressive strength and the bending stiffness). The analyses in this study were carried out for the critical wind speed of 23 m/s (i.e., Gale tornado according to the Fujita tornado scale). For each analysis, the characteristic average maxima degree of orientation of the cocowood fibrovascular bundles was varied from 0 degrees to 51 degrees . The acquired results provided a deep understanding of the cocowood optimum fibrovascular tissue system that denotes the natural evolution of the material through millions of years. The knowledge advanced from this study may also serve as concept generators for innovative biomimetic applications to improve current engineered wood products. PMID- 27555850 TI - Identification of Ice Plant (Mesembryanthemum crystallinum L.) MicroRNAs Using RNA-Seq and Their Putative Roles in High Salinity Responses in Seedlings. AB - The halophyte Mesembryanthemum crystallinum (common or crystalline ice plant) is a useful model for studying molecular mechanisms of salt tolerance. The morphology, physiology, metabolism, and gene expression of ice plant have been studied and large-scale analyses of gene expression profiling have drawn an outline of salt tolerance in ice plant. A rapid root growth to a sudden increase in salinity was observed in ice plant seedlings. Using a fluorescent dye to detect Na(+), we found that ice plant roots respond to an increased flux of Na(+) by either secreting or storing Na(+) in specialized cells. High-throughput sequencing was used to identify small RNA profiles in 3-day-old seedlings treated with or without 200 mM NaCl. In total, 135 conserved miRNAs belonging to 21 families were found. The hairpin precursor of 19 conserved mcr-miRNAs and 12 novel mcr-miRNAs were identified. After 6 h of salt stress, the expression of most mcr-miRNAs showed decreased relative abundance, whereas the expression of their corresponding target genes showed increased mRNA relative abundance. The cognate target genes are involved in a broad range of biological processes: transcription factors that regulate growth and development, enzymes that catalyze miRNA biogenesis for the most conserved mcr-miRNA, and proteins that are involved in ion homeostasis and drought-stress responses for some novel mcr-miRNAs. Analyses of the functions of target genes revealed that cellular processes, including growth and development, metabolism, and ion transport activity are likely to be enhanced in roots under salt stress. The expression of eleven conserved miRNAs and two novel miRNAs were correlated reciprocally with predicted targets within hours after salt stress exposure. Several conserved miRNAs have been known to regulate root elongation, root apical meristem activity, and lateral root formation. Based upon the expression pattern of miRNA and target genes in combination with the observation of Na(+) distribution, ice plant likely responds to increased salinity by using Na(+) as an osmoticum for cell expansion and guard cell opening. Excessive Na(+) could either be secreted through the root epidermis or stored in specialized leaf epidermal cells. These responses are regulated in part at the miRNA-mediated post-transcriptional level. PMID- 27555851 TI - Evolution of Epiphytism and Fruit Traits Act Unevenly on the Diversification of the Species-Rich Genus Peperomia (Piperaceae). AB - The species-rich genus Peperomia (Black Pepper relatives) is the only genus among early diverging angiosperms where epiphytism evolved. The majority of fruits of Peperomia release sticky secretions or exhibit hook-shaped appendages indicative of epizoochorous dispersal, which is in contrast to other flowering plants, where epiphytes are generally characterized by fruit morphological adaptations for anemochory or endozoochory. We investigate fruit characters using Cryo-SEM. Comparative phylogenetic analyses are applied for the first time to include life form and fruit character information to study diversification in Peperomia. Likelihood ratio tests uncover correlated character evolution. We demonstrate that diversification within Peperomia is not homogenous across its phylogeny, and that net diversification rates increase by twofold within the most species-rich subgenus. In contrast to former land plant studies that provide general evidence for increased diversification in epiphytic lineages, we demonstrate that the evolution of epiphytism within Peperomia predates the diversification shift. An epiphytic-dependent diversification is only observed for the background phylogeny. An elevated frequency of life form transitions between epiphytes and terrestrials and thus evolutionary flexibility of life forms is uncovered to coincide with the diversification shift. The evolution of fruits showing dispersal related structures is key to diversification in the foreground region of the phylogeny and postdates the evolution of epiphytism. We conclude that the success of Peperomia, measured in species numbers, is likely the result of enhanced vertical and horizontal dispersal ability and life form flexibility but not the evolution of epiphytism itself. PMID- 27555852 TI - Comparative Proteomics of Oxalate Downregulated Tomatoes Points toward Cross Talk of Signal Components and Metabolic Consequences during Post-harvest Storage. AB - Fruits of angiosperms evolved intricate regulatory machinery for sensorial attributes and storage quality after harvesting. Organic acid composition of storage organs forms the molecular and biochemical basis of organoleptic and nutritional qualities with metabolic specialization. Of these, oxalic acid (OA), determines the post-harvest quality in fruits. Tomato (Solanum lycopersicum) fruit has distinctive feature to undergo a shift from heterotrophic metabolism to carbon assimilation partitioning during storage. We have earlier shown that decarboxylative degradation of OA by FvOXDC leads to acid homeostasis besides increased fungal tolerance in E8.2-OXDC tomato. Here, we elucidate the metabolic consequences of oxalate down-regulation and molecular mechanisms that determine organoleptic features, signaling and hormonal regulation in E8.2-OXDC fruit during post-harvest storage. A comparative proteomics approach has been applied between wild-type and E8.2-OXDC tomato in temporal manner. The MS/MS analyses led to the identification of 32 and 39 differentially abundant proteins associated with primary and secondary metabolism, assimilation, biogenesis, and development in wild-type and E8.2-OXDC tomatoes, respectively. Next, we interrogated the proteome data using correlation network analysis that identified significant functional hubs pointing toward storage related coinciding processes through a common mechanism of function and modulation. Furthermore, physiochemical analyses exhibited reduced oxalic acid content with concomitant increase in citric acid, lycopene and marginal decrease in malic acid in E8.2-OXDC fruit. Nevertheless, E8.2-OXDC fruit maintained an optimal pH and a steady state acid pool. These might contribute to reorganization of pectin constituent, reduced membrane leakage and improved fruit firmness in E8.2-OXDC fruit with that of wild-type tomato during storage. Collectively, our study provides insights into kinetically controlled protein network, identified regulatory module for pathway formulation and provide basis toward understanding the context of storage quality maintenance as a consequence of oxalate downregulation in the sink organ. PMID- 27555853 TI - Efficient Production of a Bioactive Bevacizumab Monoclonal Antibody Using the 2A Self-cleavage Peptide in Transgenic Rice Callus. AB - Bevacizumab, a humanized monoclonal antibody (mAb) targeting to the vascular endothelial growth factor (VEGF), has been widely used in clinical practice for the treatment of multiple cancers. Bevacizumab was mostly produced by the mammalian cell expression system. We here reported the first plant-derived Bevacizumab by using transgenic rice callus as an alternative gene expression system. Codon-optimized Bevacizumab light chain (BLC) and Bevacizumab heavy chain (BHC) genes were designed, synthesized as a polyprotein with a 2A self-cleavage linker peptide from the Foot-and-mouth disease virus, cloned into a plant binary vector under a constitutive maize ubiquitin promoter, and transformed into rice nuclear genome through Agrobacterium-mediated transformation. Southern blot and western blot analyses confirmed the integration and expression of BLC and BHC genes in transgenic rice callus. Enzyme-linked immunosorbent assay (ELISA) analysis indicated that the rice-derived Bevacizumab mAb was biologically active and the recombinant mAb was expressed at high levels (160.7-242.8 mg/Kg) in transgenic rice callus. The mAb was purified by using protein A affinity chromatography and the purified antibody was tested for its binding affinity with its target human VEGF (hVEGF) antigen by ELISA. Rice callus produced Bevacizumab and a commercial Bevacizumab (Avastin) were shown to have similar binding affinity to hVEGF. These results indicated that rice callus produced Bevacizumab could have similar biological activity and might potentially be used as a cost effective biosimilar molecule in future cancer treatment. PMID- 27555854 TI - New Features on the Environmental Regulation of Metabolism Revealed by Modeling the Cellular Proteomic Adaptations Induced by Light, Carbon, and Inorganic Nitrogen in Chlamydomonas reinhardtii. AB - Microalgae are currently emerging to be very promising organisms for the production of biofuels and high-added value compounds. Understanding the influence of environmental alterations on their metabolism is a crucial issue. Light, carbon and nitrogen availability have been reported to induce important metabolic adaptations. So far, the influence of these variables has essentially been studied while varying only one or two environmental factors at the same time. The goal of the present work was to model the cellular proteomic adaptations of the green microalga Chlamydomonas reinhardtii upon the simultaneous changes of light intensity, carbon concentrations (CO2 and acetate), and inorganic nitrogen concentrations (nitrate and ammonium) in the culture medium. Statistical design of experiments (DOE) enabled to define 32 culture conditions to be tested experimentally. Relative protein abundance was quantified by two dimensional differential in-gel electrophoresis (2D-DIGE). Additional assays for respiration, photosynthesis, and lipid and pigment concentrations were also carried out. A hierarchical clustering survey enabled to partition biological variables (proteins + assays) into eight co-regulated clusters. In most cases, the biological variables partitioned in the same cluster had already been reported to participate to common biological functions (acetate assimilation, bioenergetic processes, light harvesting, Calvin cycle, and protein metabolism). The environmental regulation within each cluster was further characterized by a series of multivariate methods including principal component analysis and multiple linear regressions. This metadata analysis enabled to highlight the existence of a clear regulatory pattern for every cluster and to mathematically simulate the effects of light, carbon, and nitrogen. The influence of these environmental variables on cellular metabolism is described in details and thoroughly discussed. This work provides an overview of the metabolic adaptations contributing to maintain cellular homeostasis upon extensive environmental changes. Some of the results presented here could be used as starting points for more specific fundamental or applied investigations. PMID- 27555855 TI - Vector-Borne Bacterial Plant Pathogens: Interactions with Hemipteran Insects and Plants. AB - Hemipteran insects are devastating pests of crops due to their wide host range, rapid reproduction, and ability to transmit numerous plant-infecting pathogens as vectors. While the field of plant-virus-vector interactions has flourished in recent years, plant-bacteria-vector interactions remain poorly understood. Leafhoppers and psyllids are by far the most important vectors of bacterial pathogens, yet there are still significant gaps in our understanding of their feeding behavior, salivary secretions, and plant responses as compared to important viral vectors, such as whiteflies and aphids. Even with an incomplete understanding of plant-bacteria-vector interactions, some common themes have emerged: (1) all known vector-borne bacteria share the ability to propagate in the plant and insect host; (2) particular hemipteran families appear to be incapable of transmitting vector-borne bacteria; (3) all known vector-borne bacteria have highly reduced genomes and coding capacity, resulting in host dependence; and (4) vector-borne bacteria encode proteins that are essential for colonization of specific hosts, though only a few types of proteins have been investigated. Here, we review the current knowledge on important vector-borne bacterial pathogens, including Xylella fastidiosa, Spiroplasma spp., Liberibacter spp., and 'Candidatus Phytoplasma spp.'. We then highlight recent approaches used in the study of vector-borne bacteria. Finally, we discuss the application of this knowledge for control and future directions that will need to be addressed in the field of vector-plant-bacteria interactions. PMID- 27555856 TI - Optimization of Agroinfiltration in Pisum sativum Provides a New Tool for Studying the Salivary Protein Functions in the Pea Aphid Complex. AB - Aphids are piercing-sucking insect pests and feed on phloem sap. During feeding, aphids inject a battery of salivary proteins into host plant. Some of these proteins function like effectors of microbial pathogens and influence the outcome of plant-aphid interactions. The pea aphid (Acyrthosiphon pisum) is the model aphid and encompasses multiple biotypes each specialized to one or a few legume species, providing an opportunity to investigate the underlying mechanisms of the compatibility between plants and aphid biotypes. We aim to identify the aphid factors that determine the compatibility with host plants, hence involved in the host plant specialization process, and hypothesize that salivary proteins are one of those factors. Agrobacterium-mediated transient gene expression is a powerful tool to perform functional analyses of effector (salivary) proteins in plants. However, the tool was not established for the legume species that A. pisum feeds on. Thus, we decided to optimize the method for legume plants to facilitate the functional analyses of A. pisum salivary proteins. We screened a range of cultivars of pea (Pisum sativum) and alfalfa (Medicago sativa). None of the M. sativa cultivars was suitable for agroinfiltration under the tested conditions; however, we established a protocol for efficient transient gene expression in two cultivars of P. sativum, ZP1109 and ZP1130, using A. tumefaciens AGL-1 strain and the pEAQ-HT-DEST1 vector. We confirmed that the genes are expressed from 3 to 10 days post-infiltration and that aphid lines of the pea adapted biotype fed and reproduced on these two cultivars while lines of alfalfa and clover biotypes did not. Thus, the pea biotype recognizes these two cultivars as typical pea plants. By using a combination of ZP1109 and an A. pisum line, we defined an agroinfiltration procedure to examine the effect of in planta expression of selected salivary proteins on A. pisum fitness and demonstrated that transient expression of one candidate salivary gene increased the fecundity of the aphids. This result confirms that the agroinfiltration can be used to perform functional analyses of salivary proteins in P. sativum and consequently to study the molecular mechanisms underlying host specialization in the pea aphid complex. PMID- 27555858 TI - QTL Detection and Elite Alleles Mining for Stigma Traits in Oryza sativa by Association Mapping. AB - Stigma traits are very important for hybrid seed production in Oryza sativa, which is a self-pollinated crop; however, the genetic mechanism controlling the traits is poorly understood. In this study, we investigated the phenotypic data of 227 accessions across 2 years and assessed their genotypic variation with 249 simple sequence repeat (SSR) markers. By combining phenotypic and genotypic data, a genome-wide association (GWA) map was generated. Large phenotypic variations in stigma length (STL), stigma brush-shaped part length (SBPL) and stigma non-brush shaped part length (SNBPL) were found. Significant positive correlations were identified among stigma traits. In total, 2072 alleles were detected among 227 accessions, with an average of 8.3 alleles per SSR locus. GWA mapping detected 6 quantitative trait loci (QTLs) for the STL, 2 QTLs for the SBPL and 7 QTLs for the SNBPL. Eleven, 5, and 12 elite alleles were found for the STL, SBPL, and SNBPL, respectively. Optimal cross designs were predicted for improving the target traits. The detected genetic variation in stigma traits and QTLs provides helpful information for cloning candidate STL genes and breeding rice cultivars with longer STLs in the future. PMID- 27555859 TI - Phytohormonal Regulation of Biomass Allocation and Morphological and Physiological Traits of Leaves in Response to Environmental Changes in Polygonum cuspidatum. AB - Plants plastically change their morphological and physiological traits in response to environmental changes, which are accompanied by changes in endogenous levels of phytohormones. Although roles of phytohormones in various aspects of plant growth and development were elucidated, their importance in the regulation of biomass allocation was not fully investigated. This study aimed to determine causal relationships among changes in biomass allocation, morphological and physiological traits, and endogenous levels of phytohormones such as gibberellins (GAs) and cytokinins (CKs) in response to environmental changes in Polygonum cuspidatum. Seedlings of P. cuspidatum were grown under two light intensities, each at three nitrogen availabilities. The seedlings grown in high light intensity and high nitrogen availability (HH) were subjected to three additional treatments: Defoliating half of the leaves (Def), transferral to low nitrogen availability (LowN), or low light intensity (LowL). Biomass allocation at the whole-plant level, morphological and physiological traits of each leaf, and endogenous levels of phytohormones in each leaf and shoot apex were measured. Age dependent changes in leaf traits were also investigated. After the treatments, endogenous levels of GAs in the shoot apex and leaves significantly increased in Def, decreased in LowN, and did not change in LowL compared with HH seedlings. Among all of the seedlings, the levels of GAs in the shoot apex and leaves were strongly correlated with biomass allocation ratio between leaves and roots. The levels of GAs in the youngest leaves were highest, while the levels of CKs were almost consistent in each leaf. The levels of CKs were positively correlated with leaf nitrogen content in each leaf, whereas the levels of GAs were negatively correlated with the total non-structural carbohydrate content in each leaf. These results support our hypothesis that GAs and CKs are key regulatory factors that control biomass allocation, leaf morphology, and photosynthesis in response to changes in environmental variables in P. cuspidatum. PMID- 27555857 TI - A Snapshot of Functional Genetic Studies in Medicago truncatula. AB - In the current context of food security, increase of plant protein production in a sustainable manner represents one of the major challenges of agronomic research, which could be partially resolved by increased cultivation of legume crops. Medicago truncatula is now a well-established model for legume genomic and genetic studies. With the establishment of genomics tools and mutant populations in M. truncatula, it has become an important resource to answer some of the basic biological questions related to plant development and stress tolerance. This review has an objective to overview a decade of genetic studies in this model plant from generation of mutant populations to nowadays. To date, the three biological fields, which have been extensively studied in M. truncatula, are the symbiotic nitrogen fixation, the seed development, and the abiotic stress tolerance, due to their significant agronomic impacts. In this review, we summarize functional genetic studies related to these three major biological fields. We integrated analyses of a nearly exhaustive list of genes into their biological contexts in order to provide an overview of the forefront research advances in this important legume model plant. PMID- 27555860 TI - Two Novel AP2/EREBP Transcription Factor Genes TaPARG Have Pleiotropic Functions on Plant Architecture and Yield-Related Traits in Common Wheat. AB - AP2/EREBPs play significant roles in plant growth and development. A novel, pleiotropic TaPARG (PLANT ARCHITECTURE-RELATED GENE), a member of the AP2/EREBP transcription factor gene family, and its flanking sequences were isolated in wheat (Triticum aestivum L.). Two TaPARG genes were identified and named as TaPARG-2A and TaPARG-2D. Their amino acid sequences were highly similar especially in the functional domains. TaPARG-2A on chromosome 2A was flanked by markers Xwmc63 and Xgwm372. TaPARG-2D was mapped to chromosome 2D. Subcellular localization revealed that TaPARG-2D was localized in the nucleus. The results of tissue expression pattern, overexpression in rice, association analysis and distinct population verification jointly revealed that TaPARG functions during the entire growth cycle of wheat. Its functions include regulation of plant architecture-related and yield-related traits. Association analysis, geographic distribution and allelic frequencies suggested that favored haplotypes Hap-2A-2 and Hap-2A-3 were selected in Chinese wheat breeding programs. Both favored haplotypes might be caused by a single amino acid substitution (His/Tyr). These results suggest that TaPARG is a regulatory factor in plant growth and development, and that the favored alleles might be useful for improving plant architecture and grain yield of wheat. PMID- 27555861 TI - Development of Gene-Pyramid Lines of the Elite Restorer Line, RPHR-1005 Possessing Durable Bacterial Blight and Blast Resistance. AB - RPHR-1005, the stable restorer line of the popular medium slender (MS) grain type rice hybrid, DRRH-3 was improved in this study for resistance against bacterial blight (BB) and blast diseases through marker-assisted backcross breeding (MABB). In this study, four major resistance genes (i.e., Xa21 and Xa33 for BB resistance and Pi2 and Pi54 for blast resistance) have been transferred to RPHR-1005 using RPBio Patho-1 (possessing Xa21 + Pi2), RPBio Patho-2 (possessing Xa21 + Pi54) and FBR1-15EM (possessing Xa33) as the donors. Foreground selection was carried out using PCR-based molecular markers specific for the target resistance genes and the major fertility restorer genes, Rf3 and Rf4, while background selection was carried out using a set of parental polymorphic rice SSR markers and backcrossing was continued uptoBC2 generation. At BC2F2, plants possessing the gene combination- Xa21 + Pi2, Xa21 + Pi54 and Xa33 in homozygous condition and with >92% recovery of the recurrent parent genome (RPG) were identified and intercrossed to combine all the four resistance genes. Twenty-two homozygous, pyramid lines of RPHR-1005 comprising of three single-gene containing lines, six 2-gene containing lines, eight 3-gene containing lines, and five 4-gene containing lines were identified among the double intercross lines at F3 generation (DICF3). They were then evaluated for their resistance against BB and blast, fertility restoration ability and for key agro-morphological traits. While single gene containing lines were resistant to either BB or blast, the 2-gene, 3 gene, and 4-gene pyramid lines showed good level of resistance against both and/or either of the two diseases. Most of the 2-gene, 3-gene, and 4-gene containing pyramid lines showed yield levels and other key agro-morphological and grain quality traits comparable to the original recurrent parent and showed complete fertility restoration ability, with a few showing higher yield as compared to RPHR-1005. Further, the experimental hybrids derived by crossing the gene-pyramid lines of RPHR-1005 with APMS6A (the female parent of DRRH-3), showed heterosis levels equivalent to or higher than DRRH-3. The results of present study exemplify the utility of MABB for targeted improvement of multiple traits in hybrid rice. PMID- 27555863 TI - Impact of Grassland Reseeding, Herbicide Spraying and Ploughing on Diversity and Abundance of Soil Arthropods. AB - In order to determine the interactive effect of reseeding, herbicide spraying and ploughing on soil fauna communities, we conducted a grassland reseeding experiment combined with pre-reseed management to examine how with the whole reseeding process affects soil faunal composition. Sampling occasions and exact treatments were as follows: (1) before chemical herbicide spray; (2) after spray but before ploughing; (3) after ploughing but before reseeding; and (4) after 1 year of recovery. Our results demonstrate that, Acari and Collembola were the two soil fauna taxa with the highest abundance and accounted for around 96% of the relative total abundance among the various managements. Herbicide application tended to increase soil invertebrate abundance. Conversely, subsequent ploughing significantly reduced soil invertebrate abundance and had an obvious negative effect on soil primary and secondary decomposers, which were mainly due to the variations of Acari (especially Oribatida) and Coleoptera group abundance. Moreover, reseeding also reduced the individual number of the groups mentioned above, and favored those predators with a larger body size and individual weight. After 1 year recovery, Collembola abundance recovered to the pre-treatment levels, while with Arthropod and Acari groups were still fluctuating. PMID- 27555862 TI - The Garlic Allelochemical Diallyl Disulfide Affects Tomato Root Growth by Influencing Cell Division, Phytohormone Balance and Expansin Gene Expression. AB - Diallyl disulfide (DADS) is a volatile organosulfur compound derived from garlic (Allium sativum L.), and it is known as an allelochemical responsible for the strong allelopathic potential of garlic. The anticancer properties of DADS have been studied in experimental animals and various types of cancer cells, but to date, little is known about its mode of action as an allelochemical at the cytological level. The current research presents further studies on the effects of DADS on tomato (Solanum lycopersicum L.) seed germination, root growth, mitotic index, and cell size in root meristem, as well as the phytohormone levels and expression profile of auxin biosynthesis genes (FZYs), auxin transport genes (SlPINs), and expansin genes (EXPs) in tomato root. The results showed a biphasic, dose-dependent effect on tomato seed germination and root growth under different DADS concentrations. Lower concentrations (0.01-0.62 mM) of DADS significantly promoted root growth, whereas higher levels (6.20-20.67 mM) showed inhibitory effects. Cytological observations showed that the cell length of root meristem was increased and that the mitotic activity of meristematic cells in seedling root tips was enhanced at lower concentrations of DADS. In contrast, DADS at higher concentrations inhibited root growth by affecting both the length and division activity of meristematic cells. However, the cell width of the root meristem was not affected. Additionally, DADS increased the IAA and ZR contents of seedling roots in a dose-dependent manner. The influence on IAA content may be mediated by the up-regulation of FZYs and PINs. Further investigation into the underlying mechanism revealed that the expression levels of tomato EXPs were significantly affected by DADS. The expression levels of EXPB2 and beta-expansin precursor were increased after 3 d, and those of EXP1, EXPB3 and EXLB1 were increased after 5 d of DADS treatment (0.41 mM). This result suggests that tomato root growth may be regulated by multiple expansin genes at different developmental stages. Therefore, we conclude that the effects of DADS on the root growth of tomato seedlings are likely caused by changes associated with cell division, phytohormones, and the expression levels of expansin genes. PMID- 27555864 TI - Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones. AB - Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones. PMID- 27555865 TI - A Unified and Comprehensible View of Parametric and Kernel Methods for Genomic Prediction with Application to Rice. AB - One objective of this study was to provide readers with a clear and unified understanding of parametric statistical and kernel methods, used for genomic prediction, and to compare some of these in the context of rice breeding for quantitative traits. Furthermore, another objective was to provide a simple and user-friendly R package, named KRMM, which allows users to perform RKHS regression with several kernels. After introducing the concept of regularized empirical risk minimization, the connections between well-known parametric and kernel methods such as Ridge regression [i.e., genomic best linear unbiased predictor (GBLUP)] and reproducing kernel Hilbert space (RKHS) regression were reviewed. Ridge regression was then reformulated so as to show and emphasize the advantage of the kernel "trick" concept, exploited by kernel methods in the context of epistatic genetic architectures, over parametric frameworks used by conventional methods. Some parametric and kernel methods; least absolute shrinkage and selection operator (LASSO), GBLUP, support vector machine regression (SVR) and RKHS regression were thereupon compared for their genomic predictive ability in the context of rice breeding using three real data sets. Among the compared methods, RKHS regression and SVR were often the most accurate methods for prediction followed by GBLUP and LASSO. An R function which allows users to perform RR-BLUP of marker effects, GBLUP and RKHS regression, with a Gaussian, Laplacian, polynomial or ANOVA kernel, in a reasonable computation time has been developed. Moreover, a modified version of this function, which allows users to tune kernels for RKHS regression, has also been developed and parallelized for HPC Linux clusters. The corresponding KRMM package and all scripts have been made publicly available. PMID- 27555867 TI - An update on the epidemiological situation of spotted fever in Brazil. AB - BACKGROUND: Spotted fever is a tick-borne rickettsial disease. In Brazil, its notification to the Ministry of Health is compulsory. Since 2007, cases of spotted fever have been integrated to the Notifiable Diseases Information System, and epidemiological analyzes are part of the routines on surveillance programs. METHODS: This descriptive study updates epidemiological information on cases of spotted fever registered in Brazil between 2007 and 2015. RESULTS: In Brazil, 17,117 suspected cases of the disease were reported and 1,245 were confirmed in 12 states, mainly in Sao Paulo (550, 44.2 %) and Santa Catarina (276, 22.2 %). No geographic information was registered for 132 cases (10.6 %). Most of the infected people were men (70.9 %), mainly in rural areas (539, 43.3 %), who had contact with ticks (72.7 %). A higher number of suspected cases were registered between 2011 and 2015, but the number of confirmed cases and the incidence were relatively low. Moreover, 411 deaths were registered between 2007 and 2015, mainly in the southeastern region of the country, where the case-fatality rate was 55 %. Lack of proper filling of important fields of notification forms was also observed. CONCLUSIONS: The results showed expansion of suspected cases of spotted fever and high case-fatality rates, which could be related to diagnostic difficulties and lack of prompt treatment. These factors may comprise limitations to the epidemiological surveillance system in Brazil, hence improvement of notification and investigation are crucial to reduce morbidity and mortality due to spotted fever in Brazil. PMID- 27555868 TI - An Optimal Seed Based Compression Algorithm for DNA Sequences. AB - This paper proposes a seed based lossless compression algorithm to compress a DNA sequence which uses a substitution method that is similar to the LempelZiv compression scheme. The proposed method exploits the repetition structures that are inherent in DNA sequences by creating an offline dictionary which contains all such repeats along with the details of mismatches. By ensuring that only promising mismatches are allowed, the method achieves a compression ratio that is at par or better than the existing lossless DNA sequence compression algorithms. PMID- 27555866 TI - DNA Damage Response and Immune Defense: Links and Mechanisms. AB - DNA damage plays a causal role in numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signaling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signaling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signaling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans. PMID- 27555869 TI - Genome-Wide DNA Methylation in Mixed Ancestry Individuals with Diabetes and Prediabetes from South Africa. AB - Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings. PMID- 27555870 TI - Frequency and Influencing Factors of Rubber Dam Usage in Tianjin: A Questionnaire Survey. AB - Objective. To investigate the frequency and influencing factors of rubber dam usage for endodontic procedures among general dentistry practitioners and specialized practitioners (endodontist) in Tianjin. Methods. Three hundred questionnaires were distributed among practitioners from 3 different types of medical institutions in Tianjin. Data were collected and analysed using Chi square tests. Results. There were 63.3% of respondents who have used rubber dam (response rate 82.7%, valid response rate 76.3%). However, only 0.4% and 3.1% of them recognized using rubber dam "every time" during caries direct restoration and root canal therapy, respectively. There was no significant difference in rubber dam usage between male and female practitioners. Among the respondents, practitioners with working experience between 5 and 10 years showed the highest usage rate (76.3%), while practitioners working more than 20 years showed the lowest (53.2%). The endodontists gained the highest and the most frequent usage rate and the best rubber dam technique mastering skills. Practitioners working in those stomatological departments of general hospitals showed the lowest rubber dam usage rate. Conclusions. The prevalence of rubber dam usage in Tianjin city is still low. The practitioner's gender, years of professional experience, general or specialized field, and the type of dental setting they work for are the factors that need to be considered during making policy and executing training. PMID- 27555871 TI - Development of an Ion-Pairing Reagent and HPLC-UV Method for the Detection and Quantification of Six Water-Soluble Vitamins in Animal Feed. AB - A novel and simple method for detecting six water-soluble vitamins in animal feed using high performance liquid chromatography equipped with a photodiode array detector (HPLC/PDA) and ion-pairing reagent was developed. The chromatographic peaks of the six water-soluble vitamins were successfully identified by comparing their retention times and UV spectra with reference standards. The mobile phase was composed of buffers A (5 mM PICB-6 in 0.1% CH3COOH) and B (5 mM PICB-6 in 65% methanol). All peaks were detected using a wavelength of 270 nm. Method validation was performed in terms of linearity, sensitivity, selectivity, accuracy, and precision. The limits of detection (LODs) for the instrument employed in these experiments ranged from 25 to 197 MUg/kg, and the limits of quantification (LOQs) ranged from 84 to 658 MUg/kg. Average recoveries of the six water-soluble vitamins ranged from 82.3% to 98.9%. Method replication resulted in intraday and interday peak area variation of <5.6%. The developed method was specific and reliable and is therefore suitable for the routine analysis of water soluble vitamins in animal feed. PMID- 27555872 TI - Microbial Content of "Bowl Water" Used for Communal Handwashing in Preschools within Accra Metropolis, Ghana. AB - Objective. This study aimed at determining the microbial content of "bowl water" used for communal handwashing in preschools within the Accra Metropolis. Method. Six (6) preschools in the Accra Metropolis were involved in the study. Water samples and swabs from the hands of the preschool children were collected. The samples were analysed and tested for bacteria, fungi, parasites, and rotavirus. Results. Eight different bacteria, two different parasites, and a fungus were isolated while no rotavirus was detected. Unlike the rest of the microbes, bacterial isolates were found among samples from all the schools, with Staphylococcus species being the most prevalent (40.9%). Out of the three schools that had parasites in their water, two of them had Cryptosporidium parvum. The fungus isolated from two out of the six schools was Aspergillus niger. All bacteria isolated were found to be resistant to cotrimoxazole, ciprofloxacin, and ampicillin and susceptible to amikacin and levofloxacin. Conclusion. Although handwashing has the ability to get rid of microbes, communal handwashing practices using water in bowls could be considered a possible transmission route and may be of public concern. PMID- 27555873 TI - Simultaneous Two-Vessel Subacute Stent Thrombosis Caused by Clopidogrel Resistance from CYP2C19 Polymorphism. AB - Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism. PMID- 27555874 TI - Needle Fracture during Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Suspicious Thoracic Lymph Nodes. AB - Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is used to make a cytopathologic diagnosis of suspicious lesions located around the gastrointestinal tract. It is a safe technique with few complications. The most common complications of EUS-FNA are related to pancreatic lesions (pancreatitis, bleeding, and abdominal pain). Rare complications have been noted such as stent malfunction, air embolism, infection, neural and vascular injuries, and tumor cell seeding. There are very few studies examining equipment malfunctions. We report a case of needle fracture during the EUS-FNA of suspicious thoracic lymph nodes in a 79-year-old man investigated for unexplained weight loss. PMID- 27555875 TI - Potential factors involved in the causation of rhabdomyolysis following status asthmaticus. AB - Rhabdomyolysis is a rare but potentially fatal complication of status asthmaticus. Since the first case was reported in 1978, only a few dozen cases have been described till date. We performed a literature review with the aim to characterize the pathophysiological basis of the occurrence of rhabdomyolysis in patients with status asthmaticus. Excessive exertion of respiratory muscles, hypoxia and acidosis, electrolyte imbalance, infections, some drugs used for asthma control, use of mechanical ventilation, prolonged cardiopulmonary resuscitation, higher age of the patient and some underlying diseases or genetic factors appear to be involved in its causation. In patients with status asthmaticus, it is important to pay more attention to these factors and to closely monitor creatine kinase levels in blood so as to ensure early detection of rhabdomyolysis. PMID- 27555876 TI - Stable isotope signatures reflect dietary diversity in European forest moths. AB - BACKGROUND: Information on larval diet of many holometabolous insects remains incomplete. Carbon (C) and nitrogen (N) stable isotope analysis in adult wing tissue can provide an efficient tool to infer such trophic relationships. The present study examines whether moth feeding guild affiliations taken from literature are reflected in isotopic signatures. RESULTS: Non-metric multidimensional scaling and permutational analysis of variance indicate that centroids of dietary groups differ significantly. In particular, species whose larvae feed on mosses or aquatic plants deviated from those that consumed vascular land plants. Moth delta(15)N signatures spanned a broader range, and were less dependent on species identity than delta(13)C values. Comparison between moth samples and ostensible food sources revealed heterogeneity in the lichenivorous guild, indicating only Lithosia quadra as an obligate lichen feeder. Among root-feeding Agrotis segetum, some specimens appear to have developed on crop plants in forest-adjacent farm land. Reed-feeding stem-borers may partially rely on intermediary trophic levels such as fungal or bacterial growth. CONCLUSION: Diagnostic partitioning of moth dietary guilds based on isotopic signatures alone could not be achieved, but hypotheses on trophic relationships based on often vague literature records could be assessed with high resolution. Hence, the approach is well suited for basic categorization of moths where diet is unknown or notoriously difficult to observe (i.e. Microlepidoptera, lichen-feeders). PMID- 27555877 TI - The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism. AB - BACKGROUND: Maternal obesity may program the fetus and increase the susceptibility of the offspring to adult diseases. Metformin crosses the placenta and has been associated with decreased inflammation and reversal of fatty liver in obese leptin-deficient mice. We investigated the effects of metformin on maternal and fetal lipid metabolism and hepatic inflammation using a rat model of diet-induced obesity during pregnancy. METHODS: Female Wistar rats (6-7 weeks old) were fed normal or high calorie diets for 5 weeks. After mating with normal diet fed males, half of the high calorie-fed dams received metformin (300 mg/kg, daily); dams (8 per group) continued diets through gestational day 19. Maternal and fetal livers and fetal brains were analyzed for fatty acids and for fatty acid metabolism-related gene expression. Data were analyzed by ANOVA followed by Dunnett's post hoc testing. RESULTS: When compared to control-lean maternal livers, obesogenic-diet-exposed maternal livers showed significantly higher saturated fatty acids (14:0 and 16:0) and monounsaturated fatty acids (16:1n7 and 18:1n9) and lower polyunsaturated (18:2n6 and 20:4n6 [arachidonic acid]) and anti inflammatory n3 polyunsaturated fatty acids (18:3n3 and 22:6n3 [docosahexaenoic acid]) (p < 0.05). Metformin did not affect diet-induced changes in maternal livers. Fetal livers exposed to the high calorie diet showed significantly increased saturated fatty acids (18:0) and monounsaturated fatty acids (18:1n9 and 18:1n7) and decreased polyunsaturated fatty acids (18:2n6, 20:4n6 and 22:6n3) and anti-inflammatory n3 polyunsaturated fatty acids, along with increased gene expression of fatty acid metabolism markers (Fasn, D5d, D6d, Scd1, Lxralpha). Metformin significantly attenuated diet-induced inflammation and 18:1n9 and 22:6n3 in fetal livers, as well as n3 fatty acids (p < 0.05). Prenatal obesogenic diet exposure significantly increased fetal liver IFNgamma levels (p < 0.05), which was reversed by maternal metformin treatment (p < 0.05). CONCLUSIONS: Consumption of a high calorie diet significantly affected maternal and fetal fatty acid metabolism. It reduced anti-inflammatory polyunsaturated fatty acids in maternal and fetal livers, altered gene expression of fatty acid metabolism markers, and induced inflammation in the fetal livers. Prenatal metformin attenuated some diet-induced fatty acid changes and inflammation in the fetal livers without affecting maternal livers, suggesting that maternal metformin may impact fetal/neonatal fatty acid/lipid metabolism. PMID- 27555878 TI - The effect of inhibiting glycinamide ribonucleotide formyl transferase on the development of neural tube in mice. AB - BACKGROUND: Folate deficiency is closely related to the development of neural tube defects (NTDs). However, the exact mechanism is not completely understood. This study aims to induce murine NTDs by inhibiting one of the folate metabolic pathways, de novo purine synthesis and preliminarily investigate the potential mechanisms. The key enzyme, glycinamide ribonucleotide formyl transferase (GARFT) was inhibited by a specific inhibitor, lometrexol (DDATHF) in the pregnant mice. METHODS: Pregnant mice were intraperitoneally injected with various doses of DDATHF on gestational day 7.5 and embryos were examined for the presence of NTDs on gestational day 11.5. GARFT activity and levels of ATP, GTP, dATP and dGTP were detected in embryonic brain tissue. Proliferation and apoptosis was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemical assay and western blotting. RESULTS: 40 mg kg(-1) body weight (b/w) of DDATHF caused the highest incidence of NTDs (30.8 %) and therefore was selected as the optimal dose to establish murine NTDs. The GARFT activity and levels of ATP, GTP, dATP and dGTP in embryonic brain tissue were significantly decreased after DDATHF treatment. Furthermore, Levels of proliferation-related genes (Pcna, Foxg1 and Ptch1) were downregulated and apoptosis-related genes (Bax, Casp8 and Casp9) were upregulated. Expression of phosphohistone H3 was significantly decreased while expression of cleaved caspase-3 was greatly increased. CONCLUSIONS: Results indicate that DDATHF induced murine NTDs by disturbing purine metabolism and further led to abnormal proliferation and apoptosis. PMID- 27555879 TI - 4-aroylpiperidines and 4-(alpha-hydroxyphenyl)piperidines as selective sigma-1 receptor ligands: synthesis, preliminary pharmacological evaluation and computational studies. AB - BACKGROUND: Sigma (sigma) receptors are membrane-bound proteins characterised by an unusual promiscuous ability to bind a wide variety of drugs and their high affinity for typical neuroleptic drugs, such as haloperidol, and their potential as alternative targets for antipsychotic agents. Sigma receptors display diverse biological activities and represent potential fruitful targets for therapeutic development in combating many human diseases. Therefore, they present an interesting avenue for further exploration. It was our goal to evaluate the potential of ring opened spipethiane (1) analogues as functional ligands (agonists) for sigma receptors by chemical modification. RESULTS: Chemical modification of the core structure of the lead compound, (1), by replacement of the sulphur atom with a carbonyl group, hydroxyl group and 3-bromobenzylamine with the simultaneous presence of 4-fluorobenzoyl replacing the spirofusion afforded novel potent sigma-1 receptor ligands 7a-f, 8a-f and 9d-e. The sigma-1 receptor affinities of 7e, 8a and 8f were slightly lower than that of 1 and their selectivities for this receptor two to threefold greater than that of 1. CONCLUSIONS: It was found that these compounds have higher selectivities for sigma-1 receptors compared to 1. Quantitatitive structure-activity relationship studies revealed that sigma-1 binding is driven by hydrophobic interactions.Graphical abstractIdentified pharmacophore features for sigma binding. PMID- 27555880 TI - Characterization of a glucose-tolerant beta-glucosidase from Anoxybacillus sp. DT3-1. AB - BACKGROUND: In general, biofuel production involves biomass pretreatment and enzymatic saccharification, followed by the subsequent sugar conversion to biofuel via fermentation. The crucial step in the production of biofuel from biomass is the enzymatic saccharification. Many of the commercial cellulase enzyme cocktails, such as Spezyme((r)) CP (Genencor), AcelleraseTM 1000 (Genencor), and Celluclast((r)) 1.5L (Novozymes), are ineffectively to release free glucose from the pretreated biomass without additional beta-glucosidase. RESULTS: In this study, for the first time, a beta-glucosidase DT-Bgl gene (1359 bp) was identified in the genome of Anoxybacillus sp. DT3-1, and cloned and heterologously expressed in Escherichia coli BL21. Phylogenetic analysis indicated that DT-Bgl belonged to glycosyl hydrolase (GH) family 1. The recombinant DT-Bgl was highly active on cello-oligosaccharides and p-nitrophenyl beta-d-glucopyranoside (pNPG). The DT-Bgl was purified using an Ni-NTA column, with molecular mass of 53 kDa using an SDS-PAGE analysis. It exhibited optimum activity at 70 degrees C and pH 8.5, and did not require any tested co-factors for activation. The K m and V max values for DT-Bgl were 0.22 mM and 923.7 U/mg, respectively, with pNPG as substrate. The DT-Bgl displayed high glucose tolerance, and retained 93 % activity in the presence of 10 M glucose. CONCLUSIONS: Anoxybacillus DT-Bgl is a novel thermostable beta-glucosidase with low glucose inhibition, and converts long-chain cellodextrins to cellobiose, and further hydrolyse cellobiose to glucose. Results suggest that DT-Bgl could be useful in the development of a bioprocess for the efficient saccharification of lignocellulosic biomass. PMID- 27555881 TI - Elucidation of the co-metabolism of glycerol and glucose in Escherichia coli by genetic engineering, transcription profiling, and (13)C metabolic flux analysis. AB - BACKGROUND: Glycerol, a byproduct of biodiesel, has become a readily available and inexpensive carbon source for the production of high-value products. However, the main drawback of glycerol utilization is the low consumption rate and shortage of NADPH formation, which may limit the production of NADPH-requiring products. To overcome these problems, we constructed a carbon catabolite repression-negative DeltaptsGglpK* mutant by both blocking a key glucose PTS transporter and enhancing the glycerol conversion. The mutant can recover normal growth by co-utilization of glycerol and glucose after loss of glucose PTS transporter. To reveal the metabolic potential of the DeltaptsGglpK* mutant, this study examined the flux distributions and regulation of the co-metabolism of glycerol and glucose in the mutant. RESULTS: By labeling experiments using [1,3 (13)C]glycerol and [1-(13)C]glucose, (13)C metabolic flux analysis was employed to decipher the metabolisms of both the wild-type strain and the DeltaptsGglpK* mutant in chemostat cultures. When cells were maintained at a low dilution rate (0.1 h(-1)), the two strains showed similar fluxome profiles. When the dilution rate was increased, both strains upgraded their pentose phosphate pathway, glycolysis and anaplerotic reactions, while the DeltaptsGglpK* mutant was able to catabolize much more glycerol than glucose (more than tenfold higher). Compared with the wild-type strain, the mutant repressed its flux through the TCA cycle, resulting in higher acetate overflow. The regulation of fluxomes was consistent with transcriptional profiling of several key genes relevant to the TCA cycle and transhydrogenase, namely gltA, icdA, sdhA and pntA. In addition, cofactor fluxes and their pool sizes were determined. The DeltaptsGglpK* mutant affected the redox NADPH/NADH state and reduced the ATP level. Redox signaling activated the ArcA regulatory system, which was responsible for TCA cycle repression. CONCLUSIONS: This work employs both (13)C-MFA and transcription/metabolite analysis for quantitative investigation of the co-metabolism of glycerol and glucose in the DeltaptsGglpK* mutant. The ArcA regulatory system dominates the control of flux redistribution. The DeltaptsGglpK* mutant can be used as a platform for microbial cell factories for the production of biofuels and biochemicals, since most of fuel molecule (e.g., alcohols) synthesis requires excess reducing equivalents. PMID- 27555882 TI - Heterologous expression of family 10 xylanases from Acidothermus cellulolyticus enhances the exoproteome of Caldicellulosiruptor bescii and growth on xylan substrates. AB - BACKGROUND: The ability to deconstruct plant biomass without conventional pretreatment has made members of the genus Caldicellulosiruptor the target of investigation for the consolidated processing of lignocellulosic biomass to biofuels and bioproducts. These Gram-positive bacteria are hyperthermophilic anaerobes and the most thermophilic cellulolytic organisms so far described. They use both C5 and C6 sugars simultaneously and have the ability to grow well on xylan, a major component of plant cell walls. This is an important advantage for their use to efficiently convert biomass at yields sufficient for an industrial process. For commodity chemicals, yield from substrate is perhaps the most important economic factor. In an attempt to improve even further the ability of C. bescii to use xylan, we introduced two xylanases from Acidothermus cellulolyticus. Acel_0180 includes tandem carbohydrate-binding modules (CBM2 and CBM3) located at the C-terminus, one of which, CBM2, is not present in C. bescii. Also, the sequences of Xyn10A and Acel_0180 have very little homology with the GH10 domains present in C. bescii. For these reasons, we selected these xylanases as potential candidates for synergistic interaction with those in the C. bescii exoproteome. RESULTS: Heterologous expression of two xylanases from Acidothermus cellulolyticus in Caldicellulosiruptor bescii resulted in a modest, but significant increase in the activity of the exoproteome of C. bescii on xylan substrates. Even though the increase in extracellular activity was modest, the ability of C. bescii to grow on these substrates was dramatically improved suggesting that the xylan substrate/microbe interaction substantially increased deconstruction over the secreted free enzymes alone. CONCLUSIONS: We anticipate that the ability to efficiently use xylan, a major component of plant cell walls for conversion of plant biomass to products of interest, will allow the conversion of renewable, sustainable, and inexpensive plant feedstocks to products at high yields. PMID- 27555883 TI - The influence of insoles with a peroneal pressure point on the electromyographic activity of tibialis anterior and peroneus longus during gait. AB - BACKGROUND: Peroneus longus acts as a foot evertor and pronator, thus ensuring stability of the talocrural joint by curbing inversion movement of the rearfoot. Increased activation of the peroneus longus muscle in the stance phase could have a stabilising effect on the ankle joint. This study aimed to determine whether the activity of the peroneus longus muscle could be increased by the targeted use of a specially formed lateral pressure element in a customised orthopaedic insole. METHODS: This was a laboratory-based study that utilised a randomised crossover design. Thirty-four healthy participants walked along a walkway in neutral footwear wearing a control insole or a sensorimotor insole with a lateral pressure point adjacent to the tendon of the peroneus longus muscle. The electromyographic muscle activity of the peroneus longus and tibialis anterior muscles was measured using surface electromyography. Contact with the ground was recorded via two pressure sensors under the sole of the shoe. Muscle activity during the stance phase was analysed in the time and amplitude domains and compared statistically with paired t-tests for both insole types. RESULTS: In 27 out of the 34 participants, an additional activity peak of the peroneus longus muscle was observed in the loading response phase with the sensorimotor insole, which reached its maximum at 29.7 % (+/-4.5 %) of the stance phase. When averaged over all 34 participants, the integrated electromyographic output for the peroneus longus in the mid-stance phase revealed a significant higher activity (p < 0.001, post hoc power = 0.98, effect size: Cohen's d = 0.71) with the sensorimotor insole (18.1 +/- 11.3 % MVCs) than with the control insole (11.2 +/- 7.7 % MVCs). No significant effects were established for the other gait phases or for the tibialis anterior. CONCLUSIONS: An increase of muscle activity of the peroneus longus muscle was observed during the loading response and mid-stance phase, when orthopedic insoles with a lateral pressure point were worn. We conclude that the pressure point changes afferent information and leads to an increased peroneus longus activation in the time interval in which the pressure point exerted pressure on the peroneal tendon. PMID- 27555884 TI - The evaluation of off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) randomized controlled trial: study design and rational. AB - BACKGROUND: Off-loading is essential for diabetic foot management, but remains understudied. The evaluation of Off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) trial aims to evaluate the efficacy of a new removable device "Orthese Diabete" in the healing of diabetic foot. METHODS/DESIGN: ORTHODIAB is a French multi-centre randomized, open label trial, with a blinded end points evaluation by an adjudication committee according to the Prospective Randomized Open Blinded End-point. Main endpoints are adjudicated based on the analysis of diabetic foot photographs. Orthese Diabete is a new removable off loading orthosis (PROTEOR, France) allowing innovative functions including real time evaluation of off-loading and estimation of patients' adherence. Diabetic patients with neuropathic plantar ulcer or amputation wounds (toes or transmetatarsal) are assigned to one of 2 parallel-groups: Orthese Diabete or control group (any removable device) according to a central computer-based randomization. Study visits are scheduled for 6 months (days D7 and D14, and months M1, M2, M3, and M6). The primary endpoint is the proportion of patients whose principal ulcer is healed at M3. Secondary endpoints are: the proportion of patients whose principal ulcer is healed at M1, M2 and M6; the proportion of patients whose initial ulcers are all healed at M1, M2, M3, and M6; principal ulcer area reduction; time-related ulcer-free survival; development of new ulcers; new lower-extremity amputation; infectious complications; off-loading adherence; and patient satisfaction. The study protocol was approved by the French National Agency for Medicines and Health Products Safety, and by the ethics committee of Saint-Louis Hospital (Paris). Comprehensive study information including a Patient Information Sheet has been provided to each patient who must give written informed consent before enrolment. Monitoring, data management, and statistical analyses are providing by UMANIS Life Science (Paris), independently to the sponsor. Since 27/10/2013, 13 centres have agreed to participate in this study, 117 participants were included, and 70 have achieved the study schedules. The study completion is expected for the end of 2016, and the main results will be published in 2017. CONCLUSION: ORTHODIAB trial evaluates an innovating removable off-loading device, seeking to improve diabetic foot healing (ClinicalTrials.gov identifier: NCT01956162). PMID- 27555885 TI - Occupation and metabolic syndrome: is there correlation? A cross sectional study in different work activity occupations of German firefighters and office workers. AB - BACKGROUND: The treatment and prevention of the metabolic syndrome (MetS) is currently one of the major challenges in medicine. The impact of working conditions on metabolic risk has not been adequately studied. Our objective was to compare the prevalence of MetS and metabolic risk in two extremely different occupational groups: firefighters and office workers. METHODS: A total of 143 male subjects (97 firefighters and 46 office workers) from Germany participated in the study. Anthropometric characteristics, metabolic risk parameters as well as laboratory parameters were collected. MetS was diagnosed according to criteria of the International Diabetes Federation. RESULTS: Sedentary occupation showed a significant tendency towards obesity. Abdominal waist circumference was significantly greater in office workers than in firefighters [5.08 CI (1.44 8.71), p = 0.007]. Concerning metabolic risk factors, abnormal HDL, triglycerides, BMI, blood pressure and waist circumference values were more frequently found in office workers than in firefighters. The MetS was detected in almost 33 % of office workers as compared with only 14 % in firefighters (p = 0.015). Regarding MetS in an international comparison, the prevalence of MetS in German office workers was high and in firefighters it was extremely low. CONCLUSIONS: Sedentary occupation as an office worker is associated with a high risk of MetS. Both groups need to be made aware of the metabolic risks, and health promoting concepts such as corporate sports activities or education in healthy nutrition need to be implemented to counteract the development of the MetS and cardiovascular risk factors. PMID- 27555887 TI - Biomechanical Modeling of the Forces Applied to Closed Incisions During Single Use Negative Pressure Wound Therapy. AB - OBJECTIVES: The use of negative pressure wound therapy (NPWT) on closed surgical incisions is an emerging technology that may reduce the incidence of complications such as surgical site infections. One of the mechanisms through which incisional NPWT is thought to operate is the reduction of lateral tension across the wound. METHODS: Finite element analysis computer modeling and biomechanical testing with Syndaver SynTissueTM synthetic skin were used to explore the biomechanical forces in the presence of the PICO(?) (Smith & Nephew Ltd, Hull, United Kingdom) negative pressure wound therapy system on a sutured incision. RESULTS: Finite element analysis modeling showed that the force on an individual suture reduced to 43% of the force without negative pressure (from 1.31 to 0.56 N) at -40 mm Hg and to 31% (from 1.31 to 0.40 N) at -80 mm Hg. Biomechanical testing showed that at a pressure of -80 mm Hg, 55% more force is required for deformations in the tissue compared with the situation where no negative pressure wound therapy dressing is active. The force required for the same deformation at -120 mm Hg is only 10% greater than at -80 mm Hg, suggesting that most of the effect is achieved at -80 mm Hg. CONCLUSIONS: The results show that a canister-less single-use NPWT device is able to reduce the lateral tension across a closed incision, which may explain observed clinical reductions in surgical site complications with incisional NPWT. PMID- 27555888 TI - Forty-Year Follow-up of Full-Thickness Skin Graft After Thermal Burn Injury to the Volar Hand. AB - BACKGROUND: The hands are commonly affected in severe thermal burn injuries. Resulting contractures lead to significant loss of function. Burn contracture release and skin grafting are necessary to restore hand function. We report a case in which surgical reconstruction of a volar hand burn was performed with full-thickness skin grafting. The patient had a 40-year follow-up to assess the function and cosmesis of the repaired hand. METHODS: We report a case in which a 15-month-old boy presented after receiving third-degree burns to the left volar hand, including the flexural aspects of the index, long, and ring fingers by placing it on a hot kitchen stove burner. The patient subsequently underwent scar contracture release and full-thickness skin grafting. RESULTS: Eleven years after reconstruction, further contractures developed associated with the patient's growth, which were reconstructed with repeat full-thickness skin graft from the inguinal region. No recurrence was witnessed afterward and 40 years after initial injury, the patient maintains full activities of daily living and use of his hand in his occupation. CONCLUSIONS: There is debate regarding the superiority of split-thickness versus full-thickness grafts during reconstruction. Our case strengthens the argument for durability of a full-thickness skin graft following thermal burn injury. PMID- 27555886 TI - Cytotoxic and targeted therapy for hereditary cancers. AB - There is a number of drugs demonstrating specific activity towards hereditary cancers. For example, tumors in BRCA1/2 mutation carriers usually arise via somatic inactivation of the remaining BRCA allele, which makes them particularly sensitive to platinum-based drugs, PARP inhibitors (PARPi), mitomycin C, liposomal doxorubicin, etc. There are several molecular assays for BRCA-ness, which permit to reveal BRCA-like phenocopies among sporadic tumors and thus extend clinical indications for the use of BRCA-specific therapies. Retrospective data on high-dose chemotherapy deserve consideration given some unexpected instances of cure from metastatic disease among BRCA1/2-mutated patients. Hereditary non-polyposis colorectal cancer (HNPCC) is characterized by high-level microsatellite instability (MSI-H), increased antigenicity and elevated expression of immunosuppressive molecules. Recent clinical trial demonstrated tumor responses in HNPCC patients treated by the immune checkpoint inhibitor pembrolizumab. There are successful clinical trials on the use of novel targeted agents for the treatment or rare cancer syndromes, e.g. RET inhibitors for hereditary medullary thyroid cancer, mTOR inhibitors for tumors arising in patients with tuberous sclerosis (TSC), and SMO inhibitors for basal-cell nevus syndrome. Germ-line mutation tests will be increasingly used in the future for the choice of the optimal therapy, therefore turnaround time for these laboratory procedures needs to be significantly reduced to ensure proper treatment planning. PMID- 27555889 TI - Easy-to-Use Preservation and Application of Platelet-Rich Plasma in Combination Wound Therapy With a Gelatin Sheet and Freeze-Dried Platelet-Rich Plasma: A Case Report. AB - OBJECTIVE: Platelet-rich plasma is blood plasma enriched with platelets and contains various growth factors. Two major issues remain to be resolved in the use of platelet-rich plasma: the short biological activity after application, and the need to prepare platelet-rich plasma at each application instance. To overcome these problems, we developed a drug delivery system using gelatin hydrogel and preserved the excess platelet-rich plasma as freeze-dried platelet rich plasma. We then applied combination treatment with a gelatin sheet and platelet-rich plasma at the first instance and freeze-dried platelet-rich plasma at the second instance in the treatment of a nonhealing wound. METHODS: A 68-year old woman had suffered open fracture of her right tibia 2 years prior, and a split-thickness skin graft had been applied to repair the skin defect on the right tibia. She had multiple relapse of ulcers, and the present ulcer had not healed for 2 months. After debridement, 2 mL of activated platelet-rich plasma was applied to the ulcer, and the gelatin sheet was laid to impregnate with the platelet-rich plasma, after which the sheet was covered with a polyurethane film. Thirty-three days after the first platelet-rich plasma application, the freeze dried platelet-rich plasma was reconstituted and 2 mL of the reconstituted platelet-rich plasma was applied with a gelatin sheet. RESULTS: At 14 days after the freeze-dried platelet-rich plasma application, the wound was mostly epithelized, with the rest of the wound covered with granulation tissue. CONCLUSIONS: These findings suggest that combination wound therapy with a gelatin sheet and freeze-dried platelet-rich plasma is a promising method for resolving issues with conventional platelet-rich plasma treatment. PMID- 27555890 TI - High quality draft genome sequence of the type strain of Pseudomonas lutea OK2(T), a phosphate-solubilizing rhizospheric bacterium. AB - Pseudomonas lutea OK2(T) (=LMG 21974(T), CECT 5822(T)) is the type strain of the species and was isolated from the rhizosphere of grass growing in Spain in 2003 based on its phosphate-solubilizing capacity. In order to identify the functional significance of phosphate solubilization in Pseudomonas Plant growth promoting rhizobacteria, we describe here the phenotypic characteristics of strain OK2(T) along with its high-quality draft genome sequence, its annotation, and analysis. The genome is comprised of 5,647,497 bp with 60.15 % G + C content. The sequence includes 4,846 protein-coding genes and 95 RNA genes. PMID- 27555892 TI - Increased fecal viral content associated with obesity in mice. AB - AIM: To investigate the presence of total gut viral content in obese mice, and establish correlation with obesity associated metabolic measures and gut microbiome. METHODS: Fresh fecal samples were collected from normal and obese (Leptin deficient: Lep(ob/ob)) mice. Total viral DNA and RNA was isolated and quantified for establishing the correlation with metabolic measures and composition of gut bacterial communities. RESULTS: In this report, we found that obese mice feces have higher viral contents in terms of total viral DNA and RNA (P < 0.001). Interestingly, these increased viral DNA and RNA content were tightly correlated with metabolic measures, i.e., body weight, fat mass and fasting blood glucose. Total viral content were positively correlated with firmicutes (R(2) > 0.6), whilst negatively correlated with bacteroidetes and bifidobacteria. CONCLUSION: This study suggests the strong correlation of increased viral population into the gut of obese mice and opens new avenues to explore the role of gut virome in pathophysiology of obesity. PMID- 27555891 TI - Pharmacogenetic studies update in type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment. PMID- 27555893 TI - Effect of dimethyl sulfoxide on bond durability of fiber posts cemented with etch and-rinse adhesives. AB - PURPOSE: This study was undertaken to investigate whether use of an adhesive penetration enhancer, dimethyl sulfoxide (DMSO), improves bond stability of fiber posts to root dentin using two two-step etch-and-rinse resin cements. MATERIALS AND METHODS: Forty human maxillary central incisor roots were randomly divided into 4 groups after endodontic treatment and post space preparation, based on the fiber post/cement used with and without DMSO pretreatment. Acid-etched root dentin was treated with 5% DMSO aqueous solution for 60 seconds or with distilled water (control) prior to the application of Excite DSC/Variolink II or One-Step Plus/Duo-link for post cementation. After micro-slicing the bonded root dentin, push-out bond strength (P-OBS) test was performed immediately or after 1-year of water storage in each group. Data were analyzed using three-way ANOVA and Student's t-test (alpha=.05). RESULTS: A significant effect of time, DMSO treatment, and treatment * time interaction were observed (P<.001). DMSO did not affect immediate bonding of the two cements. Aging significantly reduced P-OBS in control groups (P<.001), while in DMSO-treated groups, no difference in P-OBS was observed after aging (P>.05). CONCLUSION: DMSO-wet bonding might be a beneficial method in preserving the stability of resin-dentin bond strength over time when fiber post is cemented with the tested etch-and-rinse adhesive cements. PMID- 27555894 TI - Effect of surface treatments on shear bond strength of resin composite bonded to CAD/CAM resin-ceramic hybrid materials. AB - PURPOSE: The purpose of this study was to assess the effect of surface treatments on shear bond strength of resin composite bonded to thermocycled and non thermocycled CAD/CAM resin-ceramic hybrid materials. MATERIALS AND METHODS: 120 specimens (10*10*2 mm) from each material were divided into 12 groups according to different surface treatments in combination with thermal aging procedures. Surface treatment methods were airborne-particle abrasion (abraded with 50 micron alumina particles), dry grinding (grinded with 125 um grain size bur), and hydrofluoric acid (9%) and silane application. According to the thermocycling procedure, the groups were assigned as non-thermocycled, thermocycled after packing composites, and thermocycled before packing composites. The average surface roughness of the non-thermocycled specimens were measured after surface treatments. After packing composites and thermocycling procedures, shear bond strength (SBS) of the specimens were tested. The results of surface roughness were statistically analyzed by 2-way Analysis of Variance (ANOVA), and SBS results were statistically analyzed by 3-way ANOVA. RESULTS: Surface roughness of GC were significantly lower than that of LU and VE (P<.05). The highest surface roughness was observed for dry grinding group, followed by airborne particle abraded group (P<.05). Comparing the materials within the same surface treatment method revealed that untreated surfaces generally showed lower SBS values. The values of untreated LU specimens showed significantly different SBS values compared to those of other surface treatment groups (P<.05). CONCLUSION: SBS was affected by surface treatments. Thermocycling did not have any effect on the SBS of the materials except acid and silane applied GC specimens, which were subjected to thermocycling before packing of the composite resin. PMID- 27555895 TI - Shear bond strength of indirect composite material to monolithic zirconia. AB - PURPOSE: This study aimed to evaluate the effect of surface treatments on bond strength of indirect composite material (Tescera Indirect Composite System) to monolithic zirconia (inCoris TZI). MATERIALS AND METHODS: Partially stabilized monolithic zirconia blocks were cut into with 2.0 mm thickness. Sintered zirconia specimens were divided into different surface treatment groups: no treatment (control), sandblasting, glaze layer & hydrofluoric acid application, and sandblasting + glaze layer & hydrofluoric acid application. The indirect composite material was applied to the surface of the monolithic zirconia specimens. Shear bond strength value of each specimen was evaluated after thermocycling. The fractured surface of each specimen was examined with a stereomicroscope and a scanning electron microscope to assess the failure types. The data were analyzed using one-way analysis of variance (ANOVA) and Tukey LSD tests (alpha=.05). RESULTS: Bond strength was significantly lower in untreated specimens than in sandblasted specimens (P<.05). No difference between the glaze layer and hydrofluoric acid application treated groups were observed. However, bond strength for these groups were significantly higher as compared with the other two groups (P<.05). CONCLUSION: Combined use of glaze layer & hydrofluoric acid application and silanization are reliable for strong and durable bonding between indirect composite material and monolithic zirconia. PMID- 27555896 TI - Microtensile bond strength and micromorphologic analysis of surface-treated resin nanoceramics. AB - PURPOSE: The aim of this study was to evaluate the influence of different surface treatment methods on the microtensile bond strength of resin cement to resin nanoceramic (RNC). MATERIALS AND METHODS: RNC onlays (Lava Ultimate) (n=30) were treated using air abrasion with and without a universal adhesive, or HF etching followed by a universal adhesive with and without a silane coupling agent, or tribological silica coating with and without a universal adhesive, and divided into 6 groups. Onlays were luted with resin cement to dentin surfaces. A microtensile bond strength test was performed and evaluated by one-way ANOVA and Tukey HSD test (alpha=.05). A nanoscratch test, field emission scanning electron microscopy, and energy dispersive X-ray spectroscopy were used for micromorphologic analysis (alpha=.05). The roughness and elemental proportion were evaluated by Kruskal-Wallis test and Mann-Whitney U test. RESULTS: Tribological silica coating showed the highest roughness, followed by air abrasion and HF etching. After HF etching, the RNC surface presented a decrease in oxygen, silicon, and zirconium ratio with increasing carbon ratio. Air abrasion with universal adhesive showed the highest bond strength followed by tribological silica coating with universal adhesive. HF etching with universal adhesive showed the lowest bond strength. CONCLUSION: An improved understanding of the effect of surface treatment of RNC could enhance the durability of resin bonding when used for indirect restorations. When using RNC for restoration, effective and systemic surface roughening methods and an appropriate adhesive are required. PMID- 27555897 TI - Tensile bond strength between auto-polymerized acrylic resin and acrylic denture teeth treated with MF-MA solution. AB - PURPOSE: This study evaluated the effect of chemical surface treatment using methyl formate-methyl acetate (MF-MA) solution on the tensile bond strength between acrylic denture teeth and auto-polymerized acrylic resin. MATERIALS AND METHODS: Seventy maxillary central incisor acrylic denture teeth for each of three different brands (Yamahachi New Ace; Major Dent; Cosmo HXL) were embedded with incisal edge downwards in auto-polymerized resin in polyethylene pipes and ground with silicone carbide paper on their ridge lap surfaces. The teeth of each brand were divided into seven groups (n=10): no surface treatment (control group), MF-MA solution at a ratio of 25:75 (v/v) for 15 seconds, 30 seconds, 60 seconds, 120 seconds, 180 seconds, and MMA for 180 seconds. Auto-polymerized acrylic resin (Unifast Trad) was applied to the ground surface and polymerized in a pressure cooker. A tensile strength test was performed with a universal testing machine. Statistical analysis of the results was performed using two-way analysis of variance (ANOVA) and post-hoc Dunnett T3 test (alpha=.05). RESULTS: The surface treatment groups had significantly higher mean tensile bond strengths compared with the control group (P<.05) when compared within the same brand. Among the surface treatment groups of each brand, there were no significantly different tensile bond strengths between the MF-MA groups and the MMA 180 second group (P>.05), except for the Yamahachi New Ace MF-MA 180-second group (P<.05). CONCLUSION: 15-second MF-MA solution can be an alternative chemical surface treatment for repairing a denture base and rebonding acrylic denture teeth with auto-polymerized acrylic resin, for both conventional and cross-linked teeth. PMID- 27555898 TI - Influence of ozone and paracetic acid disinfection on adhesion of resilient liners to acrylic resin. AB - PURPOSE: The aim of this study was to evaluate the effect of paracetic acid (PAA) and ozone disinfection on the tensile bond strength (TBS) of silicone-based resilient liners to acrylic resins. MATERIALS AND METHODS: One hundred and twenty dumbbell shaped heat-polymerized acrylic resins were prepared. From the mid segment of the specimens, 3 mm of acrylic were grinded off and separated parts were reattached by resilient liners. The specimens were divided into 2 control (control1, control7) and 4 test groups of PAA and ozone disinfection (PAA1, PAA7, ozone1 and ozone7; n=10). While control groups were immersed in distilled water for 10 min (control1) and 7 days (control7), test groups were subjected to PAA (16 g/L) or ozone rich water (4 mg/L) for 1 cycle (10 min for PAA and 60 min for ozone) per day for 7 days prior to tensile tests. Measurements of the TBS were analyzed using 3-way ANOVA and Tukey's HSD test. RESULTS: Adhesive strength of Mollosil decreased significantly by application of ozone disinfection. PAA disinfection had no negative effect on the TBS values of Mollosil and Molloplast B to acrylic resin. Single application of ozone disinfection did not have any negative effect on TBS values of Molloplast B, but prolonged exposure to ozone decreased its adhesive strength. CONCLUSION: The adhesion of resilient liners to acrylic was not adversely affected by PAA disinfection. Immersion in ozonated water significantly decreased TBS of Mollosil. Prolonged exposure to ozone negatively affects adhesion of Molloplast B to denture base materials. PMID- 27555899 TI - Three dimensional deformation of dry-stored complete denture base at room temperature. AB - PURPOSE: The aim of this study was to evaluate whether there is any typical deformation pattern existing in complete denture when it was dried by using the 3D scanner and surface matching program. MATERIALS AND METHODS: A total of 28 denture bases were fabricated with heat curing acrylic resin (each 14 upper and lower denture bases), and 14 denture bases (each 7 upper and lower denture bases) were stored in the water bottle (water stored), and another 14 denture bases were stored in the air (dry stored). Each specimen was scanned at 1(st) day after deflasking, 14(th) day after deflasking, and 28(th) day after deflasking, and digitalized. Three dimensional deformation patterns were acquired by comparison of the data within storage group using surface matching program. For evaluating differences between groups, these data were compared statisticallyusing Kruskal Wallis and Mann Whitney-U test (alpha=.05). RESULTS: When evaluating 3D deformation of denture base, obvious deformations were not found in maxillary and mandibular water storage group. However, in dry stored group, typical deformation pattern was detected as storage time passes. It occurred mostly in first two weeks. Major deformations were found in the bilateral posterior area in both maxillary and mandibular group. In maxillary dry stored group, a statistical significance was found. CONCLUSION: It was proved that in both upper and lower denture bases, dry storage caused more dimensional deformation than water storage with typical pattern. PMID- 27555900 TI - A two-short-implant-supported molar restoration in atrophic posterior maxilla: A finite element analysis. AB - PURPOSE: The aim of this study was to investigate the stress distribution of 2 short implants (2SIs) installed in a severely atrophic maxillary molar site. MATERIALS AND METHODS: Three different diameters of internal connection implants were modeled: narrow platform (NP), regular platform (RP), and wide platform (WP). The maxillary first molars were restored with one implant or two short implants. Three 2SI models (NP-oblique, NP-vertical, and NP-horizontal) and four single implant models (RP and WP in a centered or cantilevered position) were used. Axial and oblique loadings were applied on the occlusal surface of the crown. The von Mises stress values were measured at the bone-implant, peri implant bone, and implant/abutment complex. RESULTS: The highest stress distribution at the bone-implant interface and the peri-implant bone was noticed in the RP group, and the lowest stress distribution was observed in the 2SI groups. Cantilevered position showed unfavorable stress distribution with axial loading. 2SI types did not affect the stress distribution in oblique loading. The number and installation positions of the implant, rather than the bone level, influenced the stress distribution of 2SIs. The implant/abutment complex of WP presented the highest stress concentration while that of 2SIs showed the lowest stress concentration. CONCLUSION: 2SIs may be useful for achieving stable stress distribution on the surrounding bone and implant-abutment complex in the atrophic posterior maxilla. PMID- 27555901 TI - Clinical evaluation of mandibular implant overdentures via Locator implant attachment and Locator bar attachment. AB - PURPOSE: The aim of this study was to evaluate the clinical findings and patient satisfaction on implant overdenture designed with Locator implant attachment or Locator bar attachment in mandibular edentulous patients. MATERIALS AND METHODS: Implant survival rate, marginal bone loss, probing depth, peri-implant inflammation, bleeding, plaque, calculus, complications, and satisfaction were evaluated on sixteen patients who were treated with mandibular overdenture and have used it for at least 1 year (Locator implant attachment: n=8, Locator bar attachment: n=8). RESULTS: Marginal bone loss, probing depth, plaque index of the Locator bar attachment group were significantly lower than the Locator implant attachment group (P<.05). There was no significant difference on bleeding, peri implant inflammation, and patient satisfaction between the two denture types (P>.05). The replacement of the attachment components was the most common complication in both groups. Although there was no correlation between marginal bone loss and plaque index, a significant correlation was found between marginal bone loss and probing depth. CONCLUSION: The Locator bar attachment group indicates lesser marginal bone loss and need for maintenance, as compared with the Locator implant attachment group. This may be due to the splinting effect among implants rather than the types of Locator attachment. PMID- 27555902 TI - Long-term evaluation of teeth and implants during the periodic maintenance in patients with viral liver disease. AB - PURPOSE: This study was designed to investigate the maintenance of teeth and implants in patients with viral liver disease. MATERIALS AND METHODS: 316 patients without any significant systemic disease were selected as a control group. Liver disease group was consisted of 230 patients. Necessary data were collected using clinical records and panoramic radiographs. Then, the patients were subdivided into 2 groups based on the type of active dental therapy received before maintenance period (Pre-Tx). Analysis for finding statistically significant difference was performed based on the need for re-treatment of active dental therapy (Re-Tx) and change in the number of teeth (N-teeth) and implants (N-implants). RESULTS: Comparing to control group, the patients with liver disease showed higher value on N-teeth, N-implants, and Re-Tx. Statistically significant differences were found on N-teeth (P=.000) and Re-Tx (P=.000) in patients with non-surgical Pre-Tx. Analysis based on severity of liver disease showed that N-teeth and Re-Tx were directly related to severity of liver disease regardless of received type of Pre-Tx. Significant differences were found on N teeth (P=.003) and Re-Tx (P=.044) in patients with non-surgical Pre-Tx. CONCLUSION: In this study, it was concluded that liver disease might influence the loss of teeth and cause the relapse of dental disease during maintenance period in patients. A significant positive relationship between tooth and implant loss and severity of liver disease seems to exist. PMID- 27555903 TI - Fabrication of a CAD/CAM monolithic zirconia crown to fit an existing partial removable dental prosthesis. AB - Fabricating a surveyed prosthesis beneath an existing partial removable dental prosthesis (PRDP) is a challenging and time-consuming procedure. The computer aided design/computer-assisted manufacturing (CAD/CAM) technology was applied to fabricate a retrofitted, surveyed zirconia prosthesis to an existing PRDP. CAD/CAM technology enabled precise and easy replication of the contour of the planned surveyed crown on the existing abutment tooth. This technology ensured excellent adaptation and fit of newly fabricated crown to the existing PRDP with minimal adjustments. In this case report, a seventy-year-old male patient presented with fractured existing surveyed crown. Because the existing PRDP was serviceable, new crown was fabricated to the existing PRDP. PMID- 27555904 TI - HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions. AB - The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix(r) and the tetravalent (6, 11, 16 and 18) Gardasil(r) and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID- 27555905 TI - Sem analysis zirconia-ceramic adhesion interface. AB - OBJECTIVES: Modern dentistry increasingly tends to use materials aesthetically acceptable and biomimetic. Among these are zirconia and ceramics for several years, a combination that now has becoming synonym of aesthetic; however, what could be the real link between these two materials and especially its nature, remains a controversial topic debated in the literature. The aim of our study was to "underline" the type of bonding that could exist between these materials. MATERIALS AND METHODS: To investigate the nature of this bond we used a SEM microscopy (Zeiss SUPRA 25). Different bilaminar specimens: "white" zirconia Zircodent(r) and ceramic "Noritake(r)", after being tested with loading test in bending (three-point-bending) and FEM analysis, were analyzed by SEM. Fragments' analysis in closeness of the fracture's point has allowed us to be able to "see" if at large magnifications between these two materials, and without the use of linear, could exist a lasting bond and the possible type of failure that could incur. RESULTS: From our analysis of the specimens' fragments analyzed after test Equipment, it is difficult to highlight a clear margin and no-adhesion zones between the two materials, although the analysis involving fragments adjacent to the fracture that has taken place at the time of Mechanical test Equipment. CONCLUSIONS: According to our analysis and with all the clarification of the case, we can assume that you can obtain a long and lasting bond between the zirconia and ceramics. Agree to the data present in the literature, we can say that the type of bond varies according to the type of specimens and of course also the type of failure. In samples where the superstructure envelops the ceramic framework Zirconium we are in the presence of a cohesive failure, otherwise in a presence of adhesive failure. PMID- 27555906 TI - Combined orthodontic-surgical approach in the treatment of impacted maxillary canines: three clinical cases. AB - Impaction of maxillary canine is a relatively frequent orthodontic anomaly which could represent fuctional and aesthetic problems for patients. Nowadays, the conventional technique to impacted canines consists of a combined orthodontic and surgical approach, aimed to guide cuspids at the center of the alveolar ridge in a stable position and surrounded by healthy hard and soft tissues. This article presents three cases studies with different combined surgical-orthodontic approaches for the treatment of infraosseous impacted canines. An impacted maxillary canine could be guided, after adequate space is created orthodontically, to the center of the ridge through an orthodontic traction directly applied to the crown of impacted cuspid. Several surgical techniques have been proposed to expose the crown of impacted tooth. Location (buccal or palatal side) of impactation and depth influence surgical approach in order to obtain best aesthetic and functional results. PMID- 27555907 TI - Oral and dental signs of child abuse and neglect. AB - AIM: The aim of this report is to identify the main oral and dental aspects of physical and sexual abuse and dental neglect in childhood, contributing to the precocious identification and diagnosis in a dental practice. METHODS: The oral and dental manifestations were divided and classified according to the type of child abuse: physical abuse, sexual abuse, neglect. PHYSICAL ABUSE: Several studies in the literature have shown that oral or facial trauma occurs in about 50% of physically abused children; the oral cavity may be a central focus for physical abuse. Oro-facial manifestations of physical abuse include bruising, abrasions or lacerations of tongue, lips, oral mucosa, hard and soft palate, gingiva, alveolar mucosa, frenum; dental fractures, dental dislocations, dental avulsions; maxilla and mandible fractures. SEXUAL ABUSE: Although the oral cavity is a frequent site of sexual abuse in children, visible oral injuries or infections are rare. Some oral signs may represent significant indications of sexual abuse, as erythema, ulcer, vescicle with purulent drainage or pseudomembranus and condylomatous lesions of lips, tongue, palate and nose pharynx. Furthermore, if present erythema and petechiae, of unknown etiology, found on soft and hard palates junction or on the floor of the mouth, can be certainly evident proofs of forced oral sex. DENTAL NEGLECT: Oral signs of neglect are easily identifiable and are: poor oral hygiene, halitosis, Early Childhood Caries (ECC), odontogenous infections (recurrent and previous abscesses), periodontal disease, aptha lesions as a consequence of a nutritional deficiency status. Moreover, it is analyzed the assessment of bite marks because often associated with child abuse, the identification and collection of clinical evidence of this type of injury. CONCLUSION: A precocious diagnosis of child abuse, in a dental practice, could considerably contribute in the identification of violence cases and in an early intervention. PMID- 27555908 TI - Transcrestal guided sinus lift without grafting materials: a 36 months clinical prospective study. AB - PURPOSE: This study describes the ability to perform a technique for bone regeneration in maxillary posterior deficit (TGSL) without the use of bone grafting materials using a highly minimally invasive protocol. MATERIALS AND METHODS: Sixty six implants have been inserted in the sinus floor of a total of 39 patients through the transcrestal guided sinus lift technique (TGSL). All patients have been followed for at least three years in function. The drilling protocol was adapted on the basis of bone density of each implant site to achieve a torque between 45 and 55 Ncm. Healing titanium abutments tightened to 35 Ncm have been used. A CAD/CAM metal ceramics final prosthetic restoration has been generated a six months after the tissues healing and the provisional functionalization of the occlusion. Survival rate of implants and prostheses, biological and biomechanical complications, changes in marginal bone levels, and total height of alveolar crest bone before and after surgery have been evaluate and measured by the results obtained in this prospective study. It was also measured the periodontal parameters as well as levels of perception of pain by the patient during the entire recovery period. RESULTS: The result of the data of follow-up was 41.96 (24 to 36) months. Cumulative implant survival was 98.53% at 3 years. There were no biological and mechanical complications and there were no prosthetic failures during the whole period of follow-up. The Marginal Bone Loss (MBL) average during the first year of operation was from 0.33 to 0.36 mm, while the 3-year follow-up, the MBL average was 0.51 to 0.29 mm. The average of residual bone height of alveolar ridge before treatment was 6.7 to 1.6 mm (range 5.1 to 9.2 mm), while the average bone height was gained 6,4 - 1.6 mm (range 3.2 to 8.1 mm). All patients reported lower pain levels and found to have normal periodontal parameters. CONCLUSIONS: This study suggests that the use of guided surgery to perform transcrestal maxillary sinus lift to increase the sub-antral crestal height is a minimally invasive technique of success for the short and medium-term of follow-up, thus avoiding the extended treatment time and reducing the morbidity associated with the lifting of the floor of the maxillary sinus with traditional technique using bone grafting materials. Furthermore, this protocol without the use of graft materials does not vary the final outcome that have demonstrated the presence of newly formed bone around implants offering always predictable results, and giving a further reduction in the costs of the procedure rehabilitation. PMID- 27555909 TI - Analysis of Axin2 expression and function in murine models for pancreatic cancer. AB - BACKGROUND: The involvement of Wnt in carcinogenesis and progression of pancreatic cancer is currently intensely discussed. We evaluated activation of the Wnt signaling pathway by using a Wnt reporter mouse strain expressing beta galactosidase under the control of the Axin2 promotor during pancreatitis induced formation of precancerous lesions. We also evaluated activation of Wnt signaling during interaction of pancreatic cancer with the tumor stroma. RESULTS: Activation of Wnt signaling was observed during acinar-to-ductal metaplasia after chronic as well as acute pancreatitis. Activation of Wnt signaling was also noticed during growth of pancreatic cancer in an orthotopic syngeneic pancreas cancer model. Activation of Wnt signaling was, however, not observed in carcinoma associated fibroblasts, but was detected in few cell clusters inside the tumor. Genetic ablation of Axin2 significantly reduced body weight without having a major impact on blood glucose concentration. However, ablation of Axin2 had no influence on the observed beta-galactosidase positive cell clusters or on tumor weight. CONCLUSION: These data demonstrate that the Wnt signaling pathway is activated during acinar-to-ductal metaplasia after injury to the pancreas. However these data do not support a major role of Wnt signaling or of Axin2 in carcinoma associated fibroblasts and tumor growth. PMID- 27547378 TI - Biomedical Mutation Analysis (BMA): A software tool for analyzing mutations associated with antiviral resistance. AB - INTRODUCTION: Hepatitis C virus (HCV) is considered a major public health problem, with 200 million people infected worldwide. The treatment for HCV chronic infection with pegylated interferon alpha plus ribavirin inhibitors is unspecific; consequently, the treatment is effective in only 50% of patients infected. This has prompted the development of direct-acting antivirals (DAA) that target virus proteins. These DAA have demonstrated a potent effect in vitro and in vivo; however, virus mutations associated with the development of resistance have been described. OBJECTIVE: To design and develop an online information system for detecting mutations in amino acids known to be implicated in resistance to DAA. MATERIALS AND METHODS: We have used computer applications, technological tools, standard languages, infrastructure systems and algorithms, to analyze positions associated with resistance to DAA for the NS3, NS5A, and NS5B genes of HCV. RESULTS: We have designed and developed an online information system named Biomedical Mutation Analysis (BMA), which allows users to calculate changes in nucleotide and amino acid sequences for each selected sequence from conventional Sanger and cloning sequencing using a graphical interface. CONCLUSION: BMA quickly, easily and effectively analyzes mutations, including complete documentation and examples. Furthermore, the development of different visualization techniques allows proper interpretation and understanding of the results. The data obtained using BMA will be useful for the assessment and surveillance of HCV resistance to new antivirals, and for the treatment regimens by selecting those DAA to which the virus is not resistant, avoiding unnecessary treatment failures. The software is available at: http://bma.itiud.org. PMID- 27547381 TI - Case Report: ALCAPA syndrome: successful repair with an anatomical and physiological alternative surgical technique. AB - Anomalous left coronary artery from the pulmonary artery, or ALCAPA syndrome, is a rare congenital cardiac disease that can cause myocardial infarction, heart failure and even death in paediatric patients. Only few untreated patients survive until adult age. Here we present the case of a 33-year-old female patient with paroxysmal tachycardia, syncope and mild exertional dyspnoea. She was diagnosed with ALCAPA syndrome and underwent surgical correction with an alternative technique of left main coronary artery extension to the aorta. PMID- 27555912 TI - Effects of dietary protein restriction on muscle fiber characteristics and mTORC1 pathway in the skeletal muscle of growing-finishing pigs. AB - BACKGROUND: To investigate the effects of dietary crude protein (CP) restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing pigs (62.30 +/- 0.88 kg) were allotted to 3 groups and fed with the recommended adequate protein (AP, 16 % CP) diet, moderately restricted protein (MP, 13 % CP) diet and low protein (LP, 10 % CP) diet, respectively. The skeletal muscle of different locations in pigs, including longissimus dorsi muscle (LDM), psoas major muscle (PMM) and biceps femoris muscle (BFM) were collected and analyzed. RESULTS: Results showed that growing-finishing pigs fed the MP or AP diet improved (P < 0.01) the average daily gain and feed: gain ratio compared with those fed the LP diet, and the MP diet tended to increase (P = 0.09) the weight of LDM. Moreover, the ATP content and energy charge value were varied among muscle samples from different locations of pigs fed the reduced protein diets. We also observed that pigs fed the MP diet up-regulated (P < 0.05) muscular mRNA expression of all the selected key genes, except that myosin heavy chain (MyHC) IIb, MyHC IIx, while mRNA expression of ubiquitin ligases genes was not affected by dietary CP level. Additionally, the activation of mammalian target of rapamycin complex 1 (mTORC1) pathway was stimulated (P < 0.05) in skeletal muscle of the pigs fed the MP or AP diet compared with those fed the LP diet. CONCLUSION: The results suggest that the pigs fed the MP diet could catch up to the growth performance and the LDM weight of the pigs fed the AP diet, and the underlying mechanism may be partly due to the alteration in energy status, modulation of muscle fiber characteristics and mTORC1 activation as well as its downstream effectors in skeletal muscle of different locations in growing-finishing pigs. PMID- 27555913 TI - Cultural and linguistic validation of the NHQ-2 Questionnaire: a specific instrument for assessing patient's usability of inhalation devices. AB - BACKGROUND: An increasing number of inhalation devices are presently available in the market. They are differently characterized in terms of their handling and usability, both factors which may affect the outcomes of respiratory treatment. The assessment of the preference and the usability rate of all devices can be carried out by means of specific questionnaires. Before their use, the identification of errors due to the incorrect wording of questions included in the questionnaires, together with the trans-cultural reliability represents the main issues of their cultural and linguistic validation. METHODS AND RESULTS: The New Handling Questionnaire - NHQ-2 is a novel specific questionnaire aimed to measure both the preference and the usability of all kinds of inhalation devices. The method used for its validation has been summarized in the first section of the present paper, while the results of the specific validation and translation process have been described in the second section, together with the grading of improvement achieved over the process. The comprehensibility and the reproducibility rates achieved for both the Italian and the English final versions of the NHQ-2 questionnaire were very high, such as >90 % for each question included. CONCLUSIONS: The novel NHQ-2 questionnaire proved very high comprehensibility and reproducibility in both its Italian and English final versions. It can be proposed for the trans-cultural clinical use when the usability, and not only the patients' preference of devices, should be assessed. PMID- 27555914 TI - Chew and Spit (CHSP): a systematic review. AB - BACKGROUND: This systematic review is an evaluation of the empirical literature relating to the disordered eating behaviour Chew and Spit (CHSP). Current theories postulate that CHSP is a symptom exhibited by individuals with recurrent binge eating and Bulimia Nervosa. AIMS: The review aimed to identify and critically assess studies that have examined the distribution of CHSP behaviour, its relationship to eating disorders, its physical and psychosocial consequences and treatment. METHODS: A systematic database search with broad inclusion criteria, dated to January 2016 was conducted. Data were extracted by two authors and papers appraised for quality using a modified Downs and Black Quality Index. RESULTS: Nine studies met the inclusion criteria. All were of clinical samples and majority (n = 7) were of low quality. The pathological action of chewing food but not swallowing was reported more often in those with restrictive type eating disorders, such as Anorexia Nervosa, than binge eating type disorders. CHSP also was reported to be an indicator of overall severity of an eating disorder and to appear more often in younger individuals. No studies of treatment were found. CONCLUSIONS: Conclusions were limited due to the low quality and small numbers of studies based on clinical samples only. Further research is needed to address gaps in knowledge regarding the physiological, psychological, social, socioeconomic impact and treatment for those engaging in CHSP. PMID- 27555915 TI - A case of low serum insulin levels in a patient with insulinoma. AB - Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Traditionally, inappropriately elevated levels of insulin in the face of hypoglycemia are the key to diagnosis. However, contradictory levels of insulin and C-peptide do not necessarily exclude the diagnosis. A 50-year-old female was brought to our emergency department because of conscious disturbance on the previous night. She had no history of diabetes mellitus, and was not using any medications or alcohol. Laboratory data showed low sugar, a significantly low insulin level, and elevated C-peptide. After admission, she had multiple episodes of spontaneous hypoglycemia after overnight fasts without discomfort. It was considered that a neuroendocrine tumor was the source of her hypoglycemia. CT scan of the abdomen revealed a 1.1cm hypervascular nodule in the pancreatic tail. Elective laparoscopic distal pancreatectomy was incorporated into her treatment course. A 1.2*1.0cm homogenous well-encapsulated tumor was resected. We monitored her glucose levels in the outpatient clinic every month for a period of six months. She did not have another episode of spontaneous hypoglycemia. LEARNING POINTS: Insulinoma causes endogenous hypoglycemia - it cannot be ruled out in patients presenting with hypoglycemia and low insulin levels; history and imaging studies should be done for further assessmentA 24-h fast test has the same clinical significance as that of 72-h fast testC-peptide is a useful biochemical marker in addition to serum insulin, which can be used to diagnose insulinomasCT scan is used to measure the tumor size and localize the tumor. However, definitive diagnosis is only achieved through histopathologic evaluation of diseased tissue. PMID- 27555916 TI - A case of pituitary abscess presenting without a source of infection or prior pituitary pathology. AB - Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI) of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected preoperatively. She underwent transsphenoidal resection and purulent material was seen intraoperatively. Culture of the surgical specimen showed two species of alpha hemolytic Streptococcus, Staphylococcus capitis and Prevotella melaninogenica. Urine and blood cultures, dental radiographs and transthoracic echocardiogram failed to show any source of infection that could have caused the pituitary abscess. The patient was treated with 6weeks of oral metronidazole and intravenous vancomycin. After 6weeks of transsphenoidal resection and just after completion of antibiotic therapy, her headache and bitemporal hemianopsia resolved. However, nocturia and polydipsia from central diabetes insipidus and amenorrhoea from hypogonadotrophic hypogonadism persisted. LEARNING POINTS: Pituitary abscesses typically develop in patients who have other sources of infection or disruption of the normal suprasellar anatomy by either surgery, irradiation or pre-existing pathology; however, they can develop in the absence of known risk factors.Patients with pituitary abscesses typically complain of headache, visual changes and symptoms of pituitary hormone deficiencies.As other pituitary neoplasms present with similar clinical findings, the diagnosis of pituitary abscess is often not suspected until transsphenoidal resection is performed.Prompt surgical and medical treatment of pituitary abscess is necessary, which typically results in improvement in headache and visual changes; however, pituitary hormone deficiencies are typically often permanent. PMID- 27555917 TI - Exergaming (XBOX KinectTM) versus traditional gym-based exercise for postural control, flow and technology acceptance in healthy adults: a randomised controlled trial. AB - BACKGROUND: The use of exergaming is a potential alternative to traditional methods of balance training, which can be repetitive and somewhat monotonous. The purpose of this study was to assess the effects of exergaming using XBOX KinectTM versus traditional gym-based exercise with no virtual stimuli (TGB) on postural control, technology acceptance, flow experience and exercise intensity, in young healthy adults. METHODS: Fifty healthy active adults (age: 33.8 +/- 12.7 years, height: 172.9 +/- 11.9 cm, weight: 75 +/- 15.8 kg) were recruited; 44 completed both baseline and post-intervention data collection. Participants were randomised (blind card) allocation to one of two groups: (1) received balance training using the XBOX KinectTM and (2) performed traditional gym-based exercise. Exercises were matched for intensity, duration and movement patterns across groups. All participants completed three, 30-minute, exercise sessions a week for four weeks. Postural sway was measured using a KistlerTM Force platform during unipedal standing. Mean heart rate (HR) and rate of perceived exertion (RPE) were collected during each exercise session to determine and verify that intensity of exercise was matched between groups. Technology acceptance was measured with the Unified Theory of Acceptance and Use of Technology (UTAUT) and flow experience with the Flow State Scale (FSS). RESULTS: Heart rate was matched between groups and BORG RPE was significantly lower in the KinectTM group. There were significant between-group differences in postural sway in the medial-lateral direction and CoP. There were also significant differences in technology acceptance between groups for performance expectancy, social influence and behavioral intention, with higher values in the Kinect exercise group. The flow state scale showed significant differences between the groups on several dimensions, with higher values in the Kinect exercise group. CONCLUSION: Objective physiological demand of exercise (HR) was matched across groups, but the exergaming group perceived it as being less demanding and of lower intensity. This suggests that exergaming may offer an alternative method of rehabilitation exercise through improved concordance. Balance training in healthy adults using the Kinect is both accepted and intrinsically motivating. TRIAL REGISTRATION: Retrospectively registered on 27th July 2016. Trial number NCT02851017. PMID- 27555918 TI - Long working hours and overweight and obesity in working adults. AB - BACKGROUND: Previous studies have identified a link between gender and the various risk factors associated with obesity. We examined obesity risk factors in working adults to identify the effects of differences in body mass index (BMI) and percentage body fat (PBF) between women and men. METHODS: A total of 1,120 adults agreed to participate in the study. Data from 711 participants, including 411 women and 300 men, were analyzed. Multiple logistic regression analysis was used to estimate the effects of risk factors on obesity and being overweight. In addition, the least-squares (LS) means of both BMI and PBF were estimated by analysis of covariance (ANCOVA) in a generalized linear model. RESULTS: Increases in BMI and PBF were significantly related to an age > 50 years and long working hours in women after compensating for confounding factors. Using the PBF criterion, the odds ratio (OR) of being overweight or obese in women > 50 years of age who worked for > 9 h a day was 3.9 (95% confidence interval [CI], 1.05 11.00). For BMI, women who were > 50 years of age and worked for > 9 h a day were 3.82 times (95% CI, 1.31-11.14) more likely to be overweight or obese than those who were < 50 years of age and worked for < 9 h a day. CONCLUSION: Obesity in working adults was associated with > 50 years of age and long working hours in women. Further studies are needed to investigate the underlying mechanisms of this relationship and its potential implications for the prevention and management of excess weight and obesity. PMID- 27555919 TI - Differential response of tomato genotypes to Xanthomonas-specific pathogen associated molecular patterns and correlation with bacterial spot (Xanthomonas perforans) resistance. AB - Plants depend on innate immune responses to retard the initial spread of pathogens entering through stomata, hydathodes or injuries. These responses are triggered by conserved patterns in pathogen-encoded molecules known as pathogen associated molecular patterns (PAMPs). Production of reactive oxygen species (ROS) is one of the first responses, and the resulting 'oxidative burst' is considered to be a first line of defense. In this study, we conducted association analyses between ROS production and bacterial spot (BS; Xanthomonas spp.) resistance in 63 genotypes of tomato (Solanum lycopersicum L.). A luminol-based assay was performed on leaf tissues that had been treated with a flagellin 22 (flg22), flagellin 28 and a Xanthomonas-specific flg22 (flg22-Xac) peptide, to measure PAMP-induced ROS production in each genotype. These genotypes were also assessed for BS disease response by inoculation with Xanthomonas perforans, race T4. Although there was no consistent relationship between peptides used and host response to the BS, there was a significant negative correlation (r=-0.25, P<0.05) between foliar disease severity and ROS production, when flg22-Xac was used. This response could potentially be used to identify the Xanthomonas specific PRR allele in tomato, and eventually PAMP-triggered immunity loci could be mapped in a segregating population. This has potential significance in tomato improvement. PMID- 27555920 TI - Effect of floral cluster pruning on anthocyanin levels and anthocyanain-related gene expression in 'Houman' grape. AB - Lateral floral clusters were removed from the main axis of the floral clusters of 'Houman' grape plants, leaving only 3-5-cm-long region of flowers at the end of the central axis. The floral clusters were pruned at 7 days prior to flowering. The effect of the pruning on fruit quality was assessed by determining the composition and levels of anthocyanins in the fruit and anthocyanin-related gene expression. Results indicated that floral cluster pruning significantly improved the quality of the fruit by increasing berry size, fruit weight and the total content of soluble solids. Floral cluster pruning also decreased the level of titratable acidity. Sixteen different anthocyanins were detected in fruit of the pruned clusters, while only 15 were detected in fruit from unpruned clusters. The level of anthocyanins was also significantly higher in fruit of the pruned clusters than in the unpruned clusters. Anthocyanin-related gene expression was also significantly upregulated to a higher level in fruit from pruned floral clusters as compared with unpruned clusters. The upregulation was closely associated with increases in anthocyanin biosynthesis. PMID- 27555921 TI - Unaltered sequence of dental, skeletal, and sexual maturity in domestic dogs compared to the wolf. AB - BACKGROUND: It has been hypothesised that domestication altered the sequence of dental, skeletal, and sexual maturity of dogs when compared to their wolf ancestor. To test this we investigated a comprehensive sample of domestic dogs. METHODS: We documented the timing of completed eruption of permanent dentition into occlusion (dental maturity) and the timing of growth plate closure at the proximal humerus (skeletal maturity) in ontogenetic series of wolves and 15 domestic dog breeds. Data for 137 domestic dog and 64 wolf individuals were collected based on radiographs and examination of macerated bones. RESULTS: Our analyses show that domestic dogs exhibit a similar sequence of dental and skeletal maturity as the ancestral wolf. Although the absolute change of the age at attainment of sexual maturity is great in domestic dogs as compared to the wolf, the sequence of dental, skeletal, and sexual maturity is not altered as extensively, contradicting one previous hypothesis. Moreover, our data suggest that the chondrodystrophic dachshund attains skeletal maturity earlier than the non-chondrodystrophic breeds examined here. CONCLUSIONS: Domestic dogs are more wolf-like in terms of the sequence of dental, skeletal, and sexual maturation than previously hypothesised. This implies that the domestication process and/or breed formation did not have a major impact on this sequence, although the absolute values of life history variables do have a greater range of variation than in the wild wolf. PMID- 27555922 TI - Crystal structure of Ag2(MU-SCN)2(NH3)4. AB - Di-MU-thio-cyanato-bis-[diamminesilver(I)], [Ag2(MU-SCN)2(NH3)4], was synthesized by the reaction of AgSCN with anhydrous liquid ammonia. In the binuclear mol ecule, the Ag(I) atom is coordinated by two ammine ligands and the S atom of one thio-cyanate ligand. Two of these [Ag(SCN)(NH3)2] units are bridged by the S atoms of the thio-cyanate anions at longer distances, leading to a dimer with point group symmetry C 2. The distance between the Ag(I) atoms in the dimer is at 3.0927 (6) A within the range of argentophilic inter-actions. The crystal structure displays N-H?N and N-H?S hydrogen-bonding inter-actions that build up a three-dimensional network. PMID- 27555923 TI - Crystal structure of (acetato-kappaO)(ethanol-kappaO)[(9S,17S,21S,29S)-9,17,21,29 tetra-hydroxy-18,30-dioxa-octa-cyclo [18.10.0.0(2,7).0(8,19).0(9,17).0(11,16).0(21,29).0(23,28)]triaconta 1,3,5,7,11(16),12,14,19,23(28),24,26-undeca-ene-10,22-dione-kappa(3) O (18),O (21),O (22)]caesium ethanol monosolvate. AB - The title compound, [Cs(CH3COO)(C28H16O8)(C2H5OH)].C2H5OH, is the product of the complexation between one vasarene analogue [1], bis ninhydrin naphthalene-1,3 diol and CsF, where the F(-) ion has reacted with residual acetic acid (AcOH), to form a [1].CsOAc complex. The inter-molecular inter-actions with the multiple oxygen-containing functional groups of the ligand, as well as O-H?O hydrogen bonds involving the ethanol solvent mol-ecules, stabilize the complex, forming a chain along [100]. Additional parallel-displaced pi-pi stacking, with an inter planar distance of 3.669 (1) A, connect several unit cells in a three-dimensional supra-molecular structure, though, the larger size of AcO(-) (1.60 A) compared to F(-) (1.33 A) prevents the tight packing that was once achieved with other vasarene complexes of CsF. PMID- 27555925 TI - Crystal structure of poly[N,N-diethyl-2-hy-droxy-ethan-1-aminium [MU3-cyanido kappa(3) C:C:N-di-MU-cyanido-kappa(4) C:N-dicuprate(I)]]. AB - In the title compound, {(C6H16NO)[Cu2(CN)3]} n , the cyanide groups link the Cu(I) atoms into an open three-dimensional anionic network, with the mol-ecular formula Cu2(CN)3 (-). One Cu(I) atom is tetra-hedrally bound to four CN groups, and the other Cu(I) atom is bonded to three CN groups in an approximate trigonal planar coordination. The tetra-hedrally coordinated Cu(I) atoms are linked into centrosymmetric dimers by the C atoms of two end-on bridging CN groups which bring the Cu(I) atoms into close contact at 2.5171 (7) A. Two of the cyanide groups bonded to the Cu(I) atoms with trigonal-planar surrounding link the dimeric units into columns along the a axis, and the third links the columns together to form the network. The N,N-di-ethyl-ethano-lamine mol-ecules used in the synthesis have become protonated at the N atoms and are situated in cavities in the network, providing charge neutrality, with no covalent inter-actions between the cations and the anionic network. PMID- 27555924 TI - Crystal structure of di-aqua-bis-(4-tert-butyl-benzoato-kappaO)bis-(nicotinamide kappaN (1))cobalt(II) dihydrate. AB - The asymmetric unit of the mononuclear cobalt complex, [Co(C11H13O2)2(C6H6N2O)2(H2O)2].2H2O, contains one half of the complex mol-ecule, one coordinating and one non-coordinating water mol-ecule, one 4-tert-butyl benzoate (TBB) ligand and one nicotinamide (NA) ligand; the Co atom lies on an inversion centre. All ligands coordinating to the Co atom are monodentate. The four nearest O atoms around the Co atom form a slightly distorted square-planar arrangement, with the distorted octa-hedral coordination completed by the two pyridine N atoms of the NA ligands at distances of 2.1638 (11) A. The coordinating water mol-ecules are hydrogen bonded to the carboxyl O atoms [O ? O = 2.6230 (17) A], enclosing an S(6) hydrogen-bonding motif, while inter-molecular O-H?O hydrogen bonds link two of the non-coordinating water mol-ecules to the coordinating water mol-ecules and NA anions. The dihedral angle between the planar carboxyl-ate group and the adjacent benzene ring is 29.09 (10) degrees , while the benzene and pyridine rings are oriented at a dihedral angle of 88.53 (4) degrees . In the crystal, O-H?O and N-H?O hydrogen bonds link the mol-ecules, enclosing R 2 (2)(8), R 2 (2)(10) and R 4 (4)(12) ring motifs, forming layers parallel to (001). The C and H atoms of the tert-butyl group of the TBB ligand are disordered over two sets of sites with an occupancy ratio of 0.631 (5):0.369 (5). PMID- 27555926 TI - Crystal structure of bis-(benzoato-kappaO)di-butyl-tin(IV), nBu2Sn(bzo)2. AB - The title compound, [Sn(C4H9)2(C6H5COO)2], was synthesized in order to study the inter-action between di-n-butyl-tin(IV) oxide and some carb-oxy-lic acids. Di-n butyl-tin(IV) dibenzoate, nBu2Sn(obz)2, exhibits the same structural features as other diorganotin(IV) dibenzoates characterized by an unsymmetrical bidentate bonding mode [Delta(Sn-O) ? 0.4 A] of the two benzoate groups to tin. In a first approximation, the coordination sphere at tin resulting from the two stronger bonded O atoms [2.1227 (17) and 2.1405 (16) A] and the two alpha-C atoms of the n butyl groups [2.125 (3) and 2.129 (2) A] is compressed to a tetra-gonal disphenoid [<(C-Sn-C) = 148.2 (1) degrees and <(O-Sn-O) = 82.01 (6) degrees ]. This coordination sphere is expanded by the less strongly bonded two O atoms [2.507 (2) and 2.485 (2) A] to a substanti-ally distorted octa-hedron and by a weak inter-molecular Sn?O inter-action [2.943 (2) A] to a penta-gonal bipyramid with the formation of centrosymmetric dimers. The unbranched butyl groups adopt two different conformations: anti-gauche [torsion angles: 166.0 (2)-63.9 (4) degrees ] and gauche-gauche [65.0 (3)-56.3 (3) degrees ]. Inter-molecular inter actions between the dimers are restricted to O?H-C contacts (2.64 A) and van der Waals inter-actions. PMID- 27555927 TI - Crystallographic and spectroscopic characterization of (R)-O-acetyl-mandelic acid. AB - The title compound [systematic name: (R)-(-)-2-acet-oxy-2-phenyl-acetic acid], C10H10O4, is a resolved chiral ester derivative of mandelic acid. The compound contains an acetate group and a carb-oxy-lic acid group, which engage in inter molecular hydrogen bonding, forming chains extending parallel to [001] with a short donor-acceptor hydrogen-bonding distance of 2.676 (2) A. PMID- 27555928 TI - Crystal structure of hexa-kis-(dimethyl sulfoxide-kappaO)manganese(II) diiodide. AB - The asymmetric unit of the title salt, [Mn(C2H6OS)6]I2, consists of one Mn(II) ion, six O-bound dimethyl sulfoxide (DMSO) ligands and two I(-) counter-anions. The isolated complex cations have an octa-hedral configuration and are grouped in hexa-gonally arranged rows extending parallel to [100]. The two I(-) anions are located between the rows and are linked to the cations through two weak C-H?I inter-actions. PMID- 27555929 TI - Crystal structure of bis-{4-bromo-2-[(carb-amim-id-amido-imino)-meth-yl]phenolato kappa(3) N,N',O}cobalt(III) nitrate di-methyl-formamide monosolvate. AB - The title compound, [Co(C8H8BrN4O)2]NO3.C3H7NO, is formed of discrete [CoL 2](+) cations, nitrate anions and di-methyl-formamide (DMF) mol-ecules of crystallization. The cation has no crystallographically imposed symmetry. The ligand mol-ecules are deprotonated at the phenol O atom and octa-hedrally coordinate the Co(III) atoms through the azomethine N and phenolate O atoms in a mer configuration. The deprotonated ligand mol-ecules adopt an almost planar conformation. In the crystal lattice, the cations are arranged in layers in the ab plane divided by the nitrate anions and solvent mol-ecules. No pi-pi stacking is observed. All of the amine H atoms are involved in hydrogen bonding to nitrate, DMF or ligand O atoms or to one of the Br atoms, forming two-dimensional networks parallel to (100). PMID- 27555930 TI - Crystal structures of organoplatinum complexes containing alkyl-eugenoxyacetate and p-chloro-aniline. AB - In the title complexes, trans-di-chlorido-(4-chloro-aniline-kappaN){3-meth-oxy-4 meth-oxy-carbonyl-meth-oxy-1-[(2,3-eta)-prop-2-en-1-yl]benzene}-platinum(II) 0.1 hydrate, [PtCl2(C6H6ClN)(C13H16O4)].0.1H2O, (I), and trans-di-chlorido-(4-chloro aniline-kappaN){4-eth-oxy-carbonyl-meth-oxy-3-meth-oxy-1-[(2,3-eta)-prop-2-en-1 yl]benzene}-platinum(II), [PtCl2(C6H6ClN)(C14H18O4)], (II), the Pt(II) metal atom displays a slightly distorted square-planar coordination geometry defined by the aniline N atom, two chloride anions (trans-positioned) and one ethyl-enic double bond. The least-squares planes through the two aromatic ring systems make an angle of 47.3 (3) degrees for (I) and 38.6 (2) degrees for (II). Both structures show disorder for the PtCl2 fragment, in the case of (I) even further extended towards the CH2-CH=CH2 ligand. An intra-molecular C-H?Cl hydrogen bond occurs in (I). In the crystal packing of (I), which is dominated by N-H?O and C H?Cl inter-actions, a partially occupied water mol-ecule is observed on a twofold rotation axis with a refined site occupancy of 0.10 (1). A C-H?pi inter-action is also present. In (II), inversion dimers form chains along the b-axis direction by N-H?O hydrogen bonds. PMID- 27555931 TI - Crystal structure of trans-N,N'-bis-(3,5-di-tert-butyl-2-hy-droxy-phen-yl)oxamide methanol monosolvate. AB - The here crystallized oxamide was previously characterized as an unsolvated species [Jimenez-Perez et al. (2000 ?). J. Organomet. Chem. 614-615, 283-293], and is now reported with methanol as a solvent of crystallization, C30H44N2O4.CH3OH, in a different space group. The introduction of the solvent influences neither the mol-ecular symmetry of the oxamide, which remains centrosymmetric, nor the mol-ecular conformation. However, the unsolvated mol ecule crystallized as an ordered system, while many parts of the solvated crystal are disordered. The hy-droxy group in the oxamide is disordered over two chemically equivalent positions, with occupancies 0.696 (4):0.304 (4); one tert butyl group is disordered by rotation about the C-C bond, and was modelled with three sites for each methyl group, each one with occupancy 1/3. Finally, the methanol solvent, which lies on a twofold axis, is disordered by symmetry. The disorder affecting hy-droxy groups and the solvent of crystallization allows the formation of numerous supra-molecular motifs using four hydrogen bonds, with N-H and O-H groups as donors and the oxamide and methanol mol-ecule as acceptors. PMID- 27555932 TI - Crystal structure of bis-(isonicotinamide-kappaN (1))bis-(thio-cyanato kappaN)zinc. AB - The asymmetric unit of the title complex, [Zn(SCN)2(C6H6N2O)2], consists of one Zn(2+) cation located on a twofold rotation axis, as well as of one thio-cyanate anion and one neutral isonicotinamide ligand, both occupying general positions. The Zn(2+) cation is tetra-hedrally coordinated into a discrete complex by the N atoms of two symmetry-related thio-cyanate anions and by the pyridine N atoms of two isonicotinamide ligands. The complexes are linked by inter-molecular C-H?O and N-H?O, and weak inter-molecular N-H?S hydrogen-bonding inter-actions into a three-dimensional network. PMID- 27555933 TI - Crystal structures of three 6-substituted coumarin-3-carboxamide derivatives. AB - Three coumarin derivatives, viz. 6-methyl-N-(3-methyl-phen-yl)-2-oxo-2H-chromene 3-carboxamide, C18H15NO3 (1), N-(3-meth-oxy-phen-yl)-6-methyl-2-oxo-2H-chromene-3 carboxamide, C18H15NO4 (2), and 6-meth-oxy-N-(3-meth-oxy-phen-yl)-2-oxo-2H chromene-3-carboxamide, C18H15NO5 (3), were synthesized and structurally characterized. The mol-ecules display intra-molecular N-H?O and weak C-H?O hydrogen bonds, which probably contribute to the approximate planarity of the mol ecules. The supra-molecular structures feature C-H?O hydrogen bonds and pi-pi inter-actions, as confirmed by Hirshfeld surface analyses. PMID- 27555934 TI - Crystal structure of 2-(4-acetyl-anilino)-2-oxoethyl 3-(4-hy-droxy-phen yl)propionate. AB - In the title compound, C19H19NO5, the amide carbonyl O atom is positioned anti to the other two carbonyl O atoms. The 4-hy-droxy-hydro-cinnamate fragment is disordered over two positions with an occupancy ratio of 0.729 (12):0.271 (12). The N-(C=O)-C plane of the acetamide group and the acetate O-(C=O)-C plane are almost co-planar; the acetamide plane makes dihedral angles of 1.9 (6) and 16.0 (19) degrees , respectively, with the acetate planes of the major and minor occupancy components. In the crystal, N-H?O, O-H?O and C-H?O hydrogen bonds link the mol-ecules into a supra-molecular sheet structure parallel to (102). PMID- 27555935 TI - Crystal structure of an unknown solvate of (piperazine-kappaN){5,10,15,20-tetra kis-[4-(benzo-yloxy)phen-yl]porphyrinato-kappa(4) N}zinc. AB - The title compound, [Zn(C72H44N4O8)(C4H10N2)] or [Zn(TPBP)(pipz] (where TPBP and pipz are 5,10,15,20-tetra-kis-[4-(benzo-yloxy)phen-yl]porphyrinato and piperazine ligands respectively), features a distorted square-pyramidal coordin-ation geometry about the central Zn(II) atom. This central atom is chelated by the four N atoms of the porphyrinate anion and further coordinated by a nitro-gen atom of the piperazine axial ligand, which adopts a chair confirmation. The average Zn N(pyrrole) bond length is 2.078 (7) A and the Zn- N(pipz) bond length is 2.1274 (19) A. The zinc cation is displaced by 0.4365 (4) A from the N4C20 mean plane of the porphyrinate anion toward the piperazine axial ligand. This porphyrinate macrocycle exhibits major saddle and moderate ruffling deformations. In the crystal, the supra-molecular structure is made by parallel pairs of layers along (100), with an inter-layer distance of 4.100 A while the distance between two pairs of layers is 4.047 A. A region of electron density was treated with the SQUEEZE [Spek (2015 ?). Acta Cryst. C71, 9-18] procedure in PLATON following unsuccessful attempts to model it as being part of disordered n-hexane solvent and water mol-ecules. The given chemical formula and other crystal data do not take into account these solvent mol-ecules. PMID- 27555936 TI - Disodium hydrogen citrate sesquihydrate, Na2HC6H5O7(H2O)1.5. AB - The crystal structure of disodium hydrogen citrate sesquihydrate, 2Na2 (+).C6H6O7 (2-).1.5H2O, has been solved and refined using laboratory X-ray single-crystal diffraction data, and optimized using density functional techniques. The asymmetric unit contains two independent hydrogen citrate anions, four sodium cations and three water molecules. The coordination polyhedra of the cations (three with a coordination number of six, one with seven) share edges to form isolated 8-rings. The un-ionized terminal carb-oxy-lic acid groups form very strong hydrogen bonds to non-coordinating O atoms, with O?O distances of 2.46 A. PMID- 27555937 TI - Crystal structure of dimethyl 3,4,5,6-tetra-phenyl-cyclo-hexa-3,5-diene-1,2-di carboxyl-ate. AB - In the title compound, C34H28O4, the cyclo-hexa-diene ring has a screw-boat conformation with a torsion angle between the double bonds being on average ca 15 degrees [15.2 (3) and -15.3 (3) in the two independent mol-ecules]. All four phenyl rings in both mol-ecules are arranged in a propeller-like conformation. The two mol-ecules exhibit S,R- and R,S- chirality, respectively, and are connected via C-H?O inter-molecular inter-actions. In turn, these weakly bound dimers form the mol-ecular crystal. PMID- 27555938 TI - Crystal structure of ethyl 4-[(E)-(4-hy-droxy-3-meth-oxy-benzyl-idene)amino] benzoate: a p-hy-droxy Schiff base. AB - The title p-hy-droxy Schiff base, C17H17NO4, was synthesized via the condensation reaction of benzocaine with vanillin. The benzyl-idine and benzoate rings are inclined to one another by 24.58 (8) degrees , and the conformation about the C=N bond is E. In the crystal, mol-ecules are linked by O-H?N hydrogen bonds, forming zigzag chains propagating along [010]. Adjacent chains are linked by C-H?pi and weak offset pi-pi inter-actions [inter-centroid distance = 3.819 (1) A], forming sheets parallel to (10-2). PMID- 27555939 TI - Crystal structure of (E)-2-[(2-bromopyridin-3-yl)methyl-idene]-6-meth-oxy-3,4-di hydro-naphthalen-1(2H)-one and 3-[(E)-(6-meth-oxy-1-oxo-1,2,3,4-tetra-hydro naphthalen-2-ylidene)meth-yl]pyridin-2(1H)-one. AB - The title compounds C17H14BrNO2, (I), and C17H15NO3, (II), were obtained from the reaction of 6-meth-oxy-3,4-di-hydro-2H-naphthalen-1-one and 2-bromo nicotinaldehyde in ethanol. Compound (I) was the expected product and compound (II) was the oxidation product from air exposure. In the crystal structure of compound (I), there are no short contacts or hydrogen bonds. The structure does display pi-pi inter-actions between adjacent benzene rings and adjacent pyridyl rings. Compound (II) contains two independent mol-ecules, A and B, in the asymmetric unit; both are non-planar, the dihedral angles between the meth-oxy benzene and 1H-pyridin-2-one mean planes being 35.07 (9) degrees in A and 35.28 (9) degrees in B. In each mol-ecule, the 1H-pyridin-2-one unit participates in inter-molecular N-H?O hydrogen bonding to another mol-ecule of the same type (A to A or B to B). The structure also displays pi-pi inter-actions between the pyridyl and the benzene rings of non-equivalent mol-ecules (viz., A to B and B to A). PMID- 27555940 TI - Redetermination of ruizite, Ca2Mn(3+) 2[Si4O11(OH)2](OH)2.2H2O. AB - The crystal structure of ruizite, ideally Ca2Mn(3+) 2[Si4O11(OH)2](OH)2.2H2O [dicalcium dimanganese(III) tetra-silicate tetra-hydroxide dihydrate] was first determined in space group A2 with an isotropic displacement parameter model (R = 5.6%) [Hawthorne (1984 ?). Tschermaks Mineral. Petrogr. Mitt. 33, 135-146]. A subsequent refinement in space group C2/m with anisotropic displacement parameters for non-H atoms converged with R = 8.4% [Moore et al. (1985 ?). Am. Mineral. 70, 171-181]. The current study reports a redetermination of the ruizite structure by means of single-crystal X-ray diffraction data of a natural sample from the Wessels mine, Kalahari Manganese Field, Northern Cape Province, South Africa. Our data (R 1 = 3.0%) confirm that the space group of ruizite is that of the first study rather than C2/m. This work improves upon the structure reported by Hawthorne (1984 ?) in that all non-H atoms were refined with anisotropic displacement parameters and all hydrogen atoms were located. The crystal structure consists of [010] chains of edge-sharing MnO6 octa-hedra flanked by finite [Si4O11(OH)2] chains. The Ca(2+) cations are situated in the cavities of this arrangement and exhibit a coordination number of seven. PMID- 27555941 TI - Weak inter-actions in the crystal structures of two indole derivatives. AB - We describe the syntheses and crystal structures of two indole derivatives, namely a second monoclinic polymorph of ethyl 5-chloro-1H-indole-2-carboxyl-ate C11H10ClNO2, (I), and ethyl 5-chloro-3-iodo-1H-indole-2-carboxyl-ate, C11H9ClINO2, (II). In their crystal structures, both compounds form inversion dimers linked by pairs of N-H?O hydrogen bonds, which generate R 2 (2)(10) loops. The dimers are linked into double chains in (I) and sheets in (II) by a variety of weak inter-actions, including pi-pi stacking, C-I?pi, C-Cl-pi inter-actions and I?Cl halogen bonds. PMID- 27555942 TI - Crystal structure of 6-hy-droxy-5-(2-meth-oxy-phenoxy)-2,2'-bipyrimidin-4(3H) one. AB - In the title compound, C15H12N4O4, the dihedral angle between the heterocyclic rings is 12.60 (8) degrees , and that between the benzene ring and the adjacent heterocyclic ring is 85.14 (6) degrees . In the crystal, a combination of N-H?O and O-H?O hydrogen bonds link mol-ecules related by a glide plane into a C(5) C(6)[R (2) 2(9)] chain of rings, which is a distinctly different packing motif to those observed in hydrated modifications of this compound. PMID- 27555943 TI - Crystal structure of a one-dimensional looped-chain silver(I) coordination polymer: catena-poly[[silver(I)-bis-{MU-4-[1-(5'-isopropyl-[1,1':3',1''-terphen yl]-2'-yl)-1H-imidazol-2-yl]pyridine-kappa(2) N:N'}] nitrate methanol monosolvate monohydrate]. AB - In the title compound, {[Ag(C29H25N3)2]NO3.CH3OH.H2O} n , the Ag(I) cation is four-coordinated by two pyridine N atoms and two imidazole N atoms from four individual 4-(1-(5'-isopropyl-[1,1':3',1''-terphen-yl]-2'-yl)-1H-imidazol-2 yl)pyridine (i-pro-pyim) ligands. This gives rise to a highly distorted tetra hedral geometry with bond angles falling in the range 100.33 (19)-122.76 (19) degrees . Two crystallographically independent i-pro-pyim ligands (A and B) adopt very similar conformations to one another, such that the dihedral angles between the pyridyl and imidazolyl rings in the two ligands are 40.7 (3) and 42.2 (3) degrees , respectively. Each i-pro-pyim ligand binds two symmetry-related Ag(+) cations, leading to the formation of 14-membered cyclic dimers, in which the Ag(I) atoms are separated by 6.963 (2) A for the Ag-A 2-Ag dimer and 7.020 (2) A for Ag-B 2-Ag. These cyclic dimers are alternately connected to each other by sharing Ag(I) atoms, resulting in the formation of a looped-chain structure extending along the [100] direction. Moreover, adjacent looped chains are connected by inter-molecular pi-pi inter-actions [centroid-to-centroid distance = 3.689 (4) A], giving rise to the formation of a two-dimensional supra-molecular network propagating parallel to (110). Several inter-molecular C-H?O and O-H?O hydrogen bonds further contribute to the stabilization of the crystal structure. PMID- 27555944 TI - Crystal structure of racemic [(1R,2S,3R,4S,6S)-2,6-bis-(furan-2-yl)-4-hy-droxy-4 (thio-phen-2-yl)cyclo-hexane-1,3-di-yl]bis-(thio-phen-2-yl-methanone). AB - In the title compound, C28H22O5S3, the central cyclo-hexane ring adopts a chair conformation. The atoms of the furan ring attached to the 6-position of the central cyclo-hexane ring are disordered over two sets of sites with occupancies of 0.832 (5) and 0.168 (5). The hy-droxy group is disordered over two positions (at the 4- and 6-positions of the cyclo-hexane ring) in the ratio 0.832 (5):0.168 (5). In the crystal, mol-ecules are linked by C-H?O hydrogen bonds and C-H?pi inter-actions, forming layers parallel to (100). PMID- 27555945 TI - Crystal structures of (E)-N'-(2-hy-droxy-5-methyl-benzyl idene)isonicotinohydrazide and (E)-N'-(5-fluoro-2-hy-droxy-benzyl idene)isonicotinohydrazide. AB - Two derivatives of the well-known iron chelator, (E)-N'-(2-hy-droxy-benzyl idene)isonicotinohydrazide (SIH), substituted in the 5-position of the 2-hy-droxy benzene ring by a methyl and a fluorine group viz. (E)-N'-(2-hy-droxy-5-methyl benzyl-idene)isonicotinohydrazide, C14H13N3O2, (I), and (E)-N'-(5-fluoro-2-hy droxy-benzyl-idene)isonicotinohydrazide, C13H10FN3O2, (II), have been prepared and characterized by single-crystal X-ray diffraction, (1)H NMR and mass spectrometry. The mol-ecules of both compounds deviate slightly from planarity [r.m.s. deviations are 0.145 and 0.110 A for (I) and (II), respectively] and adopt an E conformation with respect to the double bond of the hydrazone bridge. In each mol-ecule, there is an intra-molecular O-H?N hydrogen bond forming an S(6) ring motif. The dihedral angles between the mean planes of the isonicotinoyl ring and the cresol ring in (I) or the fluoro-phenol ring in (II) are 10.49 (6) and 9.43 (6) degrees , respectively. In the crystals of both compounds, zigzag chains are formed via N-H?N hydrogen bonds, in the [10-1] direction for (I) and [010] for (II). In (I), the chains are linked by weak C-H?pi and pi-pi stacking inter-actions [centroid-to-centroid distances = 3.6783 (8) A; inter-planar angle = 10.94 (5) degrees ], leading to the formation of a three-dimensional supra molecular architecture. In (II), adjacent chains are connected through C-H?O hydrogen bonds to form sheets parallel to (100), which enclose R 4 (4)(30) ring motifs. The sheets are linked by weak C-H?pi and pi-pi [centroid-to-centroid distance = 3.7147 (8) A; inter-planar angle = 10.94 (5) degrees ] inter-actions, forming a three-dimensional supra-molecular architecture. PMID- 27555946 TI - Crystal structure and Hirshfeld-surface analysis of (benzene-carbo-thio-amide kappaS)bromido-bis-(tri-phenylphosphane-kappaP)silver(I). AB - The title complex, [AgBr(C7H7NS)(C18H15P)2], was obtained from the reaction of silver(I) bromide with benzene-carbo-thio-amide (C7H7NS) and tri-phenyl-phosphane (C18H15P) in the mixed solvent of aceto-nitrile and ethanol. The mononuclear complex exhibits a distorted tetra-hedral coordination geometry about the metal atom, arising from one S atom of a benzene-carbo-thio-amide ligand, two P atoms of two tri-phenyl-phosphane mol-ecules and one bromide ion. An intra-molecular N H?Br hydrogen bond is observed and in the crystal structure, inversion dimers linked by pairs of N-H?Br and C-H?Br hydrogen bonds are observed. In addition, C H?pi inter-actions occur, leading to [101] chains. Hirshfeld-surface analyses are presented and discussed. PMID- 27555947 TI - Crystal structures of bis-(phen-oxy)silicon phthalocyanines: increasing pi-pi inter-actions, solubility and disorder and no halogen bonding observed. AB - We report the syntheses and characterization of three solution-processable phen oxy silicon phthalocyanines (SiPcs), namely bis-(3-methyl-phen oxy)(phthalocyanine)silicon [(3MP)2-SiPc], C46H30N8O2Si, bis-(2-sec-butyl-phen oxy)(phthalocyanine)silicon [(2secBP)2-SiPc], C44H24I2N8O2Si, and bis-(3-iodo phen-oxy)(phthalocyanine)silicon [(3IP)2-SiPc], C52H42N8O2Si. Crystals grown of these compounds were characterized by single-crystal X-ray diffraction and the pi pi inter-actions between the aromatic SiPc cores were studied. It was determined that (3MP)2-SiPc has similar inter-actions to previously reported bis-(3,4,5-tri fluoro-phen-oxy)silicon phthalocyanines [(345 F)2-SiPc] with significant pi-pi inter-actions between the SiPc groups. (3IP)2-SiPc and (2secBP)2-SiPc both experienced a parallel stacking of two of the peripheral aromatic groups. In all three cases, the solubility of these mol-ecules was increased by the addition of phen-oxy groups while maintaining pi-pi inter-actions between the aromatic SiPc groups. The solubility of (2secBP)2-SiPc was significantly higher than other bis phen-oxy-SiPcs and this was exemplified by the higher observed disorder within the crystal structure. PMID- 27555948 TI - Li2GeMo3O8: a novel reduced molybdenum oxide containing Mo3O13 cluster units. AB - The crystal structure of the title compound, dilithium germanium trimolybdenum octa-oxide, consists of distorted hexa-gonal-close-packed oxygen layers with stacking sequence ABAC along [001] that are held together by alternating lithium germanium and molybdenum layers. The two Li(+) and Ge(4+) ions all have site symmetry 3m. and occupy, respectively, tetra-hedral and octa-hedral sites in the ratio 2:1. The Mo atom has a formal oxidation state of +3.3 and occupies an octa hedral site (site symmetry .m.) and forms strongly bonded triangular cluster units [Mo-Mo distance = 2.4728 (8) A] involving three MoO6 octa-hedra that are each shared along two edges, constituting an Mo3O13 unit. PMID- 27555949 TI - Crystal structure of 2-ethyl-4-methyl-1-(2-oxido-3,4-dioxo-cyclo-but-1-en-1-yl) 1H-imidazol-3-ium. AB - In the title inner salt molecule, C10H10N2O3, the four-membered cyclobutene ring is twisted by 7.1 (2) degrees with respect to the five-membered imidazole ring. The crystal packing exhibits an R 2 (2)(9) hydrogen-bonding ring motif through N H?O and C-H?O inter-actions. The potential non-linear optical properties were studied by a computational ab initio calculations performed at the DFT/B3LYP/6 31++G(d,p) level of theory. PMID- 27555950 TI - Crystal structure of bis-[4-(di-methyl-amino)-pyridinium] aqua-bis (oxalato)oxidovanadate(IV) dihydrate. AB - The title organic-inorganic hybrid salt, (C7H11N2)2[V(C2O4)2O(H2O)].2H2O, shows a distorted octa-hedral coordination environment for the vanadium(IV) atom in the anion (point group symmetry 2), with four O atoms from two symmetry-related chelating oxalate dianions and two O atoms in trans configuration from a coordinating water mol-ecule and a terminal vanadyl O atom. In the crystal, (001) layers of cations and anions alternate along [001]. The anionic layers are built up by inter-molecular O-H?O hydrogen bonds involving the coordinating and solvent water mol-ecules. The cationic layers are linked to the anionic layers via N-H?O hydrogen bonds between the pyridinium group and the non-coordinating O atoms of the oxalate group. The 4-(di-methyl-amino)-pyridinium cations are also engaged in pi-pi stacking with their anti-parallel neighbours [centroid-to-centroid distance = 3.686 (2) A]. Considering all supra-molecular features, a three-dimensional network structure is accomplished. PMID- 27555951 TI - Crystal structure of chlorido-[trans-1-(di-phenyl-phosphane-thioyl-kappaS)-2-(di phenyl-phosphano-yl)ethene]gold(I) di-chloro-methane hemisolvate. AB - The title compound, [AuCl(C26H22OP2S)].0.5CH2Cl2, crystallizes with a trans-O-P?P S geometry of the groups either side of the C=C double bond, which prevents any intra-molecular contact between the Au and O atoms. The Au(I) atom exhibits a nearly linear coordination [Cl-Au-S = 177.55 (4) degrees ]. The mol-ecules associate to form broad ribbons parallel to the c axis via two C-H?O, one C H?Cl(Au) and one Au?Cl inter-action. PMID- 27555952 TI - Synthesis and crystal structure of [2,7,12-trimethyl-3,7,11,17-tetra-aza-bicyclo [11.3.1]hepta-deca-1(17),13,15-triene-kappa(4) N]copper(II) bis-(perchlorate). AB - The title copper(II) complex of a pyridine-containing macrocycle (PyMAC), [Cu(C16H28N4)](ClO4)2, has been prepared. The crystal structure reveals the Cu(II) atom to be octahedrally coordinated by a tetradentate aminopyridine macrocyclic ligand surrounding the metal cation in a square-planar geometry. Two weakly bound perchlorate counter-ions occupy the axial sites above and below the macrocyclic plane. The crystal studied was refined as a two-component pseudo merohedral twin; the refined fractional contribution of the minor component is 38.77 (8). PMID- 27555953 TI - Crystal structure of the tetra-gonal polymorph of bis-(1-ethyl-3-methyl imidazolium) tetra-bromido-cadmate. AB - Both unique Cd atoms in the tetra-gonal polymorph of bis-(1-ethyl-3-methyl imidazolium) tetra-bromido-cadmate, (C6H11N2)2[CdBr4], occupy special positions (site symmetry -4). The crystal structure consists of isolated tetra-hedral [CdBr4](2-) anions which are surrounded by 1-ethyl-3-methyl-imidazolium cations. The methyl and ethyl side chains of the cations show positional disorder in a 0.590 (11):0.410 (11) ratio. In the crystal, (C6H11N2)(+) cations display three weak C-H?Br hydrogen-bond inter-actions through the imidazolium ring H atoms with the Br(-) ligands of the surrounding complex anions. The alkyl groups of the side chains are not involved in hydrogen bonding. PMID- 27555954 TI - The alluaudite-type crystal structures of Na2(Fe/Co)2Co(VO4)3 and Ag2(Fe/Co)2Co(VO4)3. AB - Single crystals of the title compounds, disodium di(cobalt/iron) cobalt tris (orthovanadate), Na2(Fe/Co)2Co(VO4)3, and disilver di(cobalt/iron) cobalt tris (orthovanadate), Ag2(Fe/Co)2Co(VO4)3, were grown from a melt consisting of stoichiometric mixtures of three metallic cation precursors and vanadium pentoxide. The difficulty to distinguish between cobalt and iron by using X-ray diffraction alone forced us to explore several models, assuming an oxidation state of +II for Co and +III for Fe and a partial cationic disorder in the Wyckoff site 8f containing a mixture of Co and Fe with a statistical distribution for the Na compound and an occupancy ratio of 0.4875:0.5125 (Co:Fe) for the Ag compound. The alluaudite-type structure is made up from [10-1] chains of [(Co,Fe)2O10] double octa-hedra linked by highly distorted [CoO6] octa-hedra via a common edge. The chains are linked through VO4 tetra-hedra, forming polyhedral sheets perpendicular to [010]. The stacking of the sheets defines two types of channels parallel to [001] where the Na(+) cations (both with full occupancy) or Ag(+) cations (one with occupancy 0.97) are located. PMID- 27555955 TI - Crystal structure of 4-methyl-2,6,7-trioxa-1-phosphabi-cyclo-[2.2.2]octa-ne. AB - The title mol-ecule, C5H9O3P, has a bi-cyclo-[2.2.2] structure with the P atom at the prow and the bridge-head C atom, with the bonded methyl group, at the stern. The three six-membered rings in the bi-cyclo-[2.2.2] structure have essentially identical good boat conformations. PMID- 27555956 TI - N'-[(1E)-(5-Nitro-furan-2-yl)methyl-idene]thio-phene-2-carbohydrazide: crystal structure and Hirshfeld surface analysis. AB - In the title carbohydrazide, C10H7N3O4S, the dihedral angle between the terminal five-membered rings is 27.4 (2) degrees , with these lying to the same side of the plane through the central CN2C(=O) atoms (r.m.s. deviation = 0.0403 A), leading to a curved mol-ecule. The conformation about the C=N imine bond [1.281 (5) A] is E, and the carbonyl O and amide H atoms are anti. In the crystal, N-H?O hydrogen bonds lead to supra-molecular chains, generated by a 41 screw-axis along the c direction. A three-dimensional architecture is consolidated by thienyl-C H?O(nitro) and furanyl-C-H?O(nitro) inter-actions, as well as pi-pi inter-actions between the thienyl and furanyl rings [inter-centroid distance = 3.515 (2) A]. These, and other, weak inter-molecular inter-actions, e.g. nitro-N-O?pi(thien yl), have been investigated by Hirshfeld surface analysis, which confirms the dominance of the conventional N-H?O hydrogen bonding to the overall mol-ecular packing. PMID- 27555957 TI - Crystal structure of di-aqua-bis-(7-di-ethyl-amino-3-formyl-2-oxo-2H-chromen-4 olato-kappa(2) O (3),O (4))zinc(II) dimethyl sulfoxide disolvate. AB - The structure of the title coordination complex, [Zn(C14H14NO4)2(H2O)2].2C2H6OS, shows that the Zn(II) cation adopts an octa-hedral geometry and lies on an inversion center. Two organic ligands occupy the equatorial positions of the coordination sphere, forming a chelate ring motif via the O atom on the formyl group and another O atom of the carbonyl group (a pseudo-beta-diketone motif). Two water mol-ecules occupy the remaining coordination sites of the Zn(II) cation in the axial positions. The water mol-ecules are each hydrogen bonded to a single dimethyl sulfoxide mol-ecule that has been entrapped in the crystal lattice. PMID- 27555958 TI - Structural characterization of two benzene-1,2-di-amine complexes of zinc chloride: a mol-ecular compound and a co-crystal salt. AB - The structures of two zinc complexes containing bidentate benzene-1,2-di-amine ligands are reported. (Benzene-1,2-di-amine-kappa(2) N,N')di-chloro-idozinc, [ZnCl2(C6H8N2)], (I), displays a distorted tetra-hedral coordination sphere for the metal cation. The di-amine ligand and the Zn atom reside on a crystallographic mirror plane. In the 1:1 co-crystal salt trans-di-aqua-bis-(4,5 di-methyl-benzene-1,2-di-amine-kappa(2) N,N')zinc chloride-4,5-di-methyl-benzene 1,2-di-amine (1/1), [Zn(C8H12N2)2(H2O)2]Cl2.2C8H12N2, (II), the zinc(II) complex cation exhibits a tetra-gonally distorted octa-hedral coordination sphere. The Zn atom sits on a crystallographically imposed inversion center and the di-amine ligands are tilted 30.63 (6) degrees with respect to the ZnN4 plane. Both complexes exhibit extensive hydrogen bonding. In (I), a stacked-sheet extended structure parallel to (101) is observed. In (II), the co-crystallized di-amine is hydrogen-bonded to the complex cation via O-H?N and N-H?N linkages. These units are in turn linked into planes along (200) by O-H?Cl and N-H?Cl hydrogen bonds. PMID- 27555959 TI - Crystal structure of 4-amino-5-chloro-2,6-di-methyl-pyrimidinium thio-phene-2,5 di-carboxyl-ate. AB - In the title salt, C6H9ClN3 (+).C6H3O4S(-), the cations and anions are linked via O-H?O and N-H?O hydrogen bonds, forming R 6 (6)(37) ring motifs that are inter connected with each other, producing sheets. Separate parallel inversion-related sheets are linked through N-H?N and pi-pi stacking inter-actions [centroid centroid distance = 3.5414 (13) A], forming double layers parallel to (101). Weak C-H?O and C-H?S hydrogen bonds, as well as C-H?pi inter-actions, connect the double layers into a three-dimensional network. PMID- 27555960 TI - Crystal structure of bis-(N,N,N',N'-tetra-methyl-guanidinium) tetra-chlorido cuprate(II). AB - In the structure of the title salt, (C5H14N3)2[CuCl4], the Cu(II) atom in the anion lies on a twofold rotation axis. The tetra-chlorido-cuprate(II) anion adopts a flattened tetra-hedral coordination environment and inter-acts electrostatically with the tetra-methyl-guanidinium cation. The crystal packing is additionally consolidated through N-H?Cl and C-H?Cl hydrogen bonds, resulting in a three-dimensional network structure. PMID- 27555961 TI - Crystal structure of non-centrosymmetric bis-(4-meth-oxy-benzyl-ammonium) tetra chlorido-zincate. AB - The structure of the title non-centrosymmetric organic-inorganic hybrid salt, (C8H12NO)2[ZnCl4], consists of two 4-meth-oxy-benzyl-ammonium cations sandwiched between anionic layers, formed by isolated tetra-chlorido-zincate tetra-hedra. The double layers extend parallel to the ac plane. The crystal packing is assured by Coulombic inter-actions and by a complex N-H?Cl and C-H?Cl hydrogen-bonding system mostly involving the positively charged ammonium groups and the chloride ligands of the isolated tetra-hedral [ZnCl4](2-) units. One of the methyl-ene ammonium groups is disordered over two sets of sites in a 0.48 (2):0.52 (2) ratio. The crystal investigated was twinned by non-merohedry with a twin component ratio of 0.738 (2):0.262 (2). PMID- 27555962 TI - Two polymorphs of trans-[3-(3-nitro-phen-yl)oxiran-2-yl](phen-yl)methanone. AB - The title compound, C15H11NO4, crystallizes in two polymorphic forms, centrosymmetric monoclinic and chiral ortho-rhom-bic. The geometry of the mol ecules in the two polymorphs is slightly different, possibly due to inter molecular inter-actions. There are no classical hydrogen bonding in these two structures. However, a number of C-H?O inter-molecular inter-actions, involving both O atoms of the nitro as well the benzoyl groups, stabilize the crystal structures. PMID- 27555963 TI - Crystal structure of Cr-bearing Mg3BeAl8O16, a new polytype of magnesiotaaffeite 2N'2S. AB - The crystal structure of a new polytype of magnesiotaaffeite-2N'2S, ideally Mg3BeAl8O16 (trimagnesium beryllium octa-aluminium hexa-deca-oxide), is described in space-group symmetry P-3m1. It has been identified in a fragment of a mineral sample from Burma (Myanmar). The new polytype is composed of two Mg2Al4O8 (S)- and two BeMgAl4O8 (N')-modules in a stacking sequence N'SSN'' which differs from the N'SN'S-stacking sequence of the known magnesiotaaffeite-2N'2S polytype. The crystal structure can be derived from a close-packed arrangement of O atoms and is discussed with regard to its polytypism and its Cr(3+) chromophore content. PMID- 27555964 TI - Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis. AB - Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage. PMID- 27555965 TI - Classification of SD-OCT Volumes Using Local Binary Patterns: Experimental Validation for DME Detection. AB - This paper addresses the problem of automatic classification of Spectral Domain OCT (SD-OCT) data for automatic identification of patients with DME versus normal subjects. Optical Coherence Tomography (OCT) has been a valuable diagnostic tool for DME, which is among the most common causes of irreversible vision loss in individuals with diabetes. Here, a classification framework with five distinctive steps is proposed and we present an extensive study of each step. Our method considers combination of various preprocessing steps in conjunction with Local Binary Patterns (LBP) features and different mapping strategies. Using linear and nonlinear classifiers, we tested the developed framework on a balanced cohort of 32 patients. Experimental results show that the proposed method outperforms the previous studies by achieving a Sensitivity (SE) and a Specificity (SP) of 81.2% and 93.7%, respectively. Our study concludes that the 3D features and high-level representation of 2D features using patches achieve the best results. However, the effects of preprocessing are inconsistent with different classifiers and feature configurations. PMID- 27555966 TI - The Blockade of IL6 Counterparts the Osmolar Stress-Induced Apoptosis in Human Conjunctival Epithelial Cells. AB - To determine the effect of hyperosmolarity on cell survival/apoptosis of conjunctival epithelial cells and evaluate the possible role of IL6, Wong Kilbourne derivative of Chang conjunctival cell line (WKD) was used in this study. Confluent cells were incubated under different osmolarity (290 mOsm and 500 mOsm) with or without neutralizing IL6 antibody (50 ng/mL). The expression of IL6 level was measured in the supernatant of each conditioned medium. Cell viability/apoptosis assay was performed using Annexin V/Propidium Iodide (PI) and Cell Counting Kit-8 (CCK-8). Western blot was conducted to measure the abundance of apoptotic markers and IL6 related downstream signaling pathway. The concentration of IL6 showed time-dependent increase in cells treated with 500 mOsm. Although apoptosis of WKD cell is increased in treated 500 mOsm for 24 h, apoptosis reduced in WKD cell treated 500 mOsm with anti-IL6 for 24 h. Anti-IL6 inhibited the activation of JAK-STAT signaling pathway, which was induced by hyperosmolarity. Hyperosmolar condition induced apoptosis in conjunctival epithelial cells, along with increase of IL6 production. IL6 neutralizing antibody inhibited apoptosis and JAK-STAT signaling in hyperosmolar condition. These findings suggested that IL6 may be involved in apoptotic change and in hyperosmolarity. PMID- 27555967 TI - Management of Maternal Cardiac Arrest in the Third Trimester of Pregnancy: A Simulation-Based Pilot Study. AB - Objective. To evaluate confidence, knowledge, and competence after a simulation based curriculum on maternal cardiac arrest in an Obstetrics & Gynecologic (OBGYN) residency program. Methods. Four simulations with structured debriefing focusing on high yield causes and management of maternal cardiac arrest were executed. Pre- and post-individual knowledge tests (KT) and confidence surveys (CS) were collected along with group scores of critical performance steps evaluated by content experts for the first and final simulations. Results. Significant differences were noted in individual KT scores (pre: 58.9 +/- 8.9 versus post: 72.8 +/- 6.1, p = 0.01) and CS total scores (pre: 22.2 +/- 6.4 versus post: 29.9 +/- 3.4, p = 0.007). Significant differences were noted in airway management, p = 0.008; appropriate cycles of drug/shock-CPR, p = 0.008; left uterine displacement, p = 0.008; and identifying causes of cardiac arrest, p = 0.008. Nonsignificant differences were noted for administration of appropriate drugs/doses, p = 0.074; chest compressions, p = 0.074; bag-mask ventilation before intubation, p = 0.074; and return of spontaneous circulation identification, p = 0.074. Groups remained noncompetent in team leader tasks and considering therapeutic hypothermia. Conclusion. This study demonstrated improved OBGYN resident knowledge, confidence, and competence in the management of third trimester maternal cardiac arrest. Several skills, however, will likely require more longitudinal curricular exposure and training to develop and maintain proficiency. PMID- 27555968 TI - Male Partner's Involvement in HIV Counselling and Testing and Associated Factors among Partners of Pregnant Women in Gondar Town, Northwest Ethiopia. AB - Background. Despite the existence of several programmes promoting male involvement in HIV counselling and testing during their wife's pregnancy as a part of PMTCT, few men have heeded the call. The aim of this study was to assess male partner's involvement in HCT and its associated factors. Methods. This study was based on institution based cross-sectional study design that used systematic random sampling technique. A total of 416 partners were interviewed in the data collection. Multivariable logistic regression model was fitted to identify the independent predictors. Result. In this study, the prevalence of male involvement in HCT was found to be 40.1% (95% CI: 35.3%-44.7%). The independent predictors of male involvement were partners who were younger, were cohabitant, were with multigravida wives, were knowledgeable on route of mother-to-child transmission, and discussed HCT. Conclusion. The prevalence of male involvement in HCT was found to be suboptimal compared to similar studies in Ethiopia. There is a need of interventions on partners who are older, separated, and with lower gravidity wife. Awareness creation campaign should also be created on the route of mother to-child transmission of HIV and on the importance of discussion with wife. PMID- 27555969 TI - Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behcet's Disease. AB - Behcet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behcet's disease was described by Hulusi Behcet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behcet's disease is based on International Criteria of Behcet's Disease (ICBD). The present paper describes a case report of Behcet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID- 27555970 TI - Replacement of Anterior Composite Resin Restorations Using Conservative Ceramics for Occlusal and Periodontal Rehabilitation: An 18-Month Clinical Follow-Up. AB - This case report describes a patient with discolored and fractured composite resin restorations on the anterior teeth in whom substitution was indicated. After wax-up and mock-up, the composite was removed and replaced with minimally invasive ceramic laminates. An established and predictable protocol was performed using resin cement. Minimally invasive ceramic restorations are increasingly being used to replace composite restorations. This treatment improves the occlusal and periodontal aspects during the planning and restorative phases, such as anterior guides, and laterality can be restored easily with ceramic laminates. In addition, the surface smoothness and contour of ceramic restorations do not affect the health of the surrounding periodontal tissues. Here we present the outcome after 18 months of clinical follow-up in a patient in whom composite resin restorations in the anterior teeth were replaced with minimally invasive ceramic laminates. PMID- 27555971 TI - Ultrasound-Guided Forearm Nerve Blocks: A Novel Application for Pain Control in Adult Patients with Digit Injuries. AB - Phalanx fractures and interphalangeal joint dislocations commonly present to the emergency department. Although these orthopedic injuries are not complex, the four-point digital block used for anesthesia during the reduction can be painful. Additionally, cases requiring prolonged manipulation or consultation for adequate reduction may require repeat blockade. This case series reports four patients presenting after mechanical injuries resulting in phalanx fracture or interphalangeal joint dislocations. These patients received an ultrasound-guided peripheral nerve block of the forearm with successful subsequent reduction. To our knowledge, use of ultrasound-guided peripheral nerve blocks of the forearm for anesthesia in reduction of upper extremity digit injuries in adult patients in the emergency department setting has not been described before. PMID- 27555972 TI - Campylobacter Pouchitis Mimicking the Appearance of Crohn's Disease. AB - An unusual case of campylobacter pouchitis resembling the endoscopic appearance of Crohn's disease is reported. PMID- 27555973 TI - The Association of Streptococcus gallolyticus Subspecies pasteurianus Bacteremia with the Detection of Premalignant and Malignant Colonic Lesions. AB - Streptococcus gallolyticus subspecies (subsp.) gallolyticus (formerly bovis biotype I) bacteremia has been associated with colonic adenocarcinoma. The bovis species underwent reclassification in 2003. Subtypes of gallolyticus are associated with colonic malignancy but are less frequent, resulting in less awareness. A 71-year-old male admitted with worsening lower back pain and fevers. Initial vital signs and laboratory data were within normal limits. MRI revealed lumbosacral osteomyelitis and antibiotics were initiated. Blood cultures showed Streptococcus species, prompting a transesophageal echocardiogram (TEE) revealing vegetations on the mitral and aortic valves. The etiology for his endocarditis was unclear. A colonoscopy was suggested, but his clinical instability made such a procedure intolerable. Final cultures revealed Streptococcus gallolyticus subsp. pasteurianus (previously bovis biotype II). After antibiotic completion he underwent aortic grafting with valve replacements. Later, he was readmitted for Streptococcus bacteremia. After a negative TEE, colonoscopy revealed a 2.5 * 3 cm cecal tubulovillous adenoma with high-grade dysplasia suspicious for his origin of infection. Clinicians understand the link between Streptococcus gallolyticus subsp. gallolyticus (bovis type I) and malignancy, but the new speciation may be unfamiliar. There are no guidelines for managing S. gallolyticus subsp. pasteurianus bacteremia; therefore a colonoscopy should be considered when no source is identified. PMID- 27555974 TI - Tuberculous Empyema Necessitatis in a 40-Year-Old Immunocompetent Male. AB - Empyema necessitans (EN) is a kind of empyema that diffuses to extrapleural space and can involve chest pain. Tuberculosis (TB) is the most common cause of EN. This disease can be found in both immunocompromised and immunocompetent individuals but is usually seen in the immunocompromised individuals. Because of long duration and ambiguous symptoms of the disease, diagnosis can be hard. The disease can be treated both medically and surgically. Missing the disease can lead to undesirable effects on patient's condition and health care setting. This problem can be seen in endemic area in which controlling of TB is hard. Report of the disease in local health care center for desirable treatment and health maintenance is necessary. We explained a rare case of pulmonary TB in a patient that was healthy in other fields and just showed the minimum systemic symptoms. The patient came with a mass in lower part of back of chest cage, with a mild pain. The imaging survey showed EN. Smear and Ziehl-Neelsen stains from subcutaneous aspiration were positive for TB. This case showed importance of clinical view and awareness of this silent but serious disease in endemic area especially for TB. PMID- 27555975 TI - Delayed Axillary Artery Occlusion after Reverse Total Shoulder Arthroplasty. AB - Axillary artery injury has been associated with shoulder dislocation and surgery. We describe a case of delayed axillary artery occlusion after reverse total shoulder arthroplasty. The injury was confirmed by Doppler and angiography and was treated with angioplasty and stenting. Early recognition and treatment of this injury are mandatory for patients' recovery. PMID- 27555976 TI - Acute Failure of a Glenoid Component in Anatomic Shoulder Arthroplasty. AB - Glenoid loosening is the most common cause of failure in primary total shoulder arthroplasty (TSA) and often occurs years after the initial surgery. It is rare for a glenoid component to fail acutely. Several case reports of complete glenoid dissociation appear in the literature. It is important to report these failures to identify technical errors or component design flaws to improve outcomes in TSA. In this case report, we present an unrecognized acute failure of a cemented hybrid glenoid component at the time of surgery. PMID- 27555977 TI - Severe Hydronephrosis and Perinephric Urinoma with Rupture of Renal Fornix Secondary to Postoperative Urinary Retention following Laparoscopic Umbilical Hernia Repair. AB - Postoperative urinary retention (POUR) is a known complication following a variety of procedures, with a reported incidence of 2.1-3.8% in general surgery and up to 52% in anorectal surgery. We report a case of POUR in a female resulting in severe unilateral hydronephrosis with a perinephric urinoma due to a ruptured fornix. The extent of hydroureter caused an axial rotation upon itself producing further outflow obstruction. This phenomenon of an anatomical ureter deformity secondary to urinary retention resulting in a ruptured fornix is an unusual occurrence. The patient underwent a percutaneous nephrogram where a stiff guidewire was successfully passed into the bladder by interventional radiology (IR) and allowed for placement of an indwelling ureteral stent. The case presentation, diagnostic evaluation, and therapeutic intervention are discussed. PMID- 27555978 TI - Cardiac Arrhythmias: Update on Mechanisms and Clinical Managements. PMID- 27555979 TI - Extraction Efficiency of Different Solvents and LC-UV Determination of Biogenic Amines in Tea Leaves and Infusions. AB - Biogenic amines (BAs), that is, spermine, spermidine, putrescine, histamine, tyramine, beta-phenylethylamine, cadaverine, and serotonin, have been determined in several samples of tea leaves, tea infusions, and tea drinks by LC-UV method after derivatization with dansyl chloride. Different extraction solvents have been tested and TCA 5% showed better analytical performances in terms of linearity, recovery percentages, LOD, LOQ, and repeatability than HCl 0.1 M and HClO4 0.1 M and was finally exploited for the quantitative determination of BAs in all samples. In tea leaves total BAs concentration ranged from 2.23 MUg g(-1) to 11.24 MUg g(-1) and PUT (1.05-2.25 MUg g(-1)) and SPD (1.01-1.95 MUg g(-1)) were always present, while SER (nd-1.56 MUg g(-1)), HIS (nd-2.44 MUg g(-1)), and SPM (nd-1.64 MUg g(-1)) were detected more rarely. CAD and PHE were determined in few samples at much lower concentrations while none of the samples contained TYR. Tea infusions showed the same trend with total BAs concentrations never exceeding 80.7 MUg L(-1). Black teas showed higher amounts of BAs than green teas and organic and decaffeinated samples always contained much lower BAs levels than their conventional counterparts. PMID- 27555980 TI - Congenital Chikungunya Virus Infection after an Outbreak in Salvador, Bahia, Brazil. AB - There is little information about the congenital chikungunya virus (CHIKV) transmission. We describe two cases of well-documented congenital CHIKV infection in Salvador-Brazil, where CHIKV has been identified since 2014. The outbreak in the city led to the clinical CHIKV diagnoses of both pregnant women 2 days before delivery. Urine and blood samples from the mothers and newborns were collected and tested for reverse transcription-polymerase chain reaction (PCR) analysis for Zika, dengue, and CHIKV. Both neonates and mothers had positive urine and serum PCR results for CHIKV. The newborns had significant perinatal complications and were admitted to the neonatal intensive care unit. The purpose of our case report is to show how severe congenital CHIKV infection can be and the importance to include CHIKV infection in the differential diagnosis of neonatal sepsis when mothers have clinical signs of the disease and live in an affected area. PMID- 27555981 TI - Correlation Between Aneurysm Size and Hemodynamics in One Individual with Multiple Small Intracranial Aneurysms. AB - Objective A large number of cases are needed in the patient-specific modeling of intracranial aneurysms to establish the statistical significance due to individual variation of risk factors that are difficult to account for. However, these risk factors are critical in hemorrhage risk as demonstrated in large clinical studies. Rupture risks for aneurysms in an individual are easier to compare because these aneurysms are under the same physiological environment, and their only differences are the local hemodynamic factors associated with their anatomic locations. Methods Eight small aneurysms (< 7 mm) from one individual were analyzed using patient-specific hemodynamic modeling. Four scenarios with different perfusion assumptions were performed to account for the flow rate at two smaller communicating arteries. Wall shear stresses (WSS) at these aneurysms were compared to determine their relationship with the aneurysm size. Results Each of the three largest aneurysms is either the most proximal or distal aneurysm in a given artery so that blood pressure does not have a direct influence on aneurysm size. No wall shear stress-derived hemodynamic variables are found to be related to aneurysm size. Discussion A study of multiple aneurysms from one individual offers a unique opportunity to examine various hemodynamic factors without selection biases. Aneurysms greater than 4 mm (Group 1) have a higher product of maximum WSS and area of low WSS; aneurysms smaller than 4 mm (Group 2) have a lower product of maximum WSS and area of low WSS. In addition, aneurysm size is linearly correlated with the flow rate at the parent artery in each group. PMID- 27555982 TI - Neurological Manifestations of Brucellosis in an Indian Population. AB - Brucellosis is a zoonotic disease causing serious public health problems in countries of the Middle-East and developing countries like India. Neurobrucellosis is one of the devastating complications of this re-emerging zoonosis. The objective of this review was to identify the neurological manifestations of Brucellosis in an Indian population and bring into light the effective modalities used for treating neurobrucellosis. A systematic review of the scientific literature reported in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines was conducted. Three databases (PubMed, IndMed, and ScienceDirect) were used to analyze retrospectively case reports of sufficient quality for data extraction (from the last 15 years, 2002-2016), and relevant literature was reviewed. Most of the cases had a definite history of exposure to Brucella through occupational contact with cattle, drinking raw milk, or living near unhygienic abattoir or even trips to epidemic areas outside India. The common presentations include fever, meningitis, brisk deep-tendon reflexes, extensor plantars, sensory deficit usually below the twelfth thoracic vertebral level, weakness of lower limbs, ocular signs of papilledema, and retrobulbar neuritis. The usual systemic findings associated were hepatosplenomegaly and weight-loss. Neurobrucellosis needs to be kept in mind in the differential diagnosis of fever of unknown origin involving neurological symptoms and systemic involvement. Prognosis is good if there is a combination of antibiotics, each with different mechanisms of action given in full dose. Suitable measures for its prevention are also suggested. PMID- 27555983 TI - Can We CanMEDS? Intangible Learning Through Tangible Simulation Case Development. AB - The Royal College CanMEDS framework has become a guide for medical school curricula. This framework aims to improve patient care by identifying and explaining seven key roles that physicians must fulfill in order to deliver high quality healthcare to their patients. While medical schools incorporate these roles in their teaching processes, students can also apply them outside the classroom. Here, we describe a unique model developed at Memorial University of Newfoundland's Tuckamore Simulation Research Collaborative (TSRC), where students develop simulation cases with the guidance of expert mentors and apply the Royal College CanMEDS framework to writing clinical simulations. PMID- 27555984 TI - Having Your Cake and Eating It Too: Combining SBRT and Multi-agent Chemotherapy in Locally Advanced Pancreatic Cancer. AB - We read with great interest the results of the LAP07 study comparing capecitabine based chemoradiation with gemcitabine-based therapy for non-progressive locally advanced pancreatic cancer (LAPC), following four months of gemcitabine-based therapy. The results, consistent with previous data, showed that standard chemoradiation improves local control (LC) but not overall survival. In this brief editorial, we emphasize that LC may still be very important in LAPC, as up to 30% of patients with LAPC may die from locally progressive disease. This is particularly likely to be true as systemic therapies continue to improve in efficacy. We very briefly review the data in support of stereotactic body radiotherapy (SBRT) for LAPC, which has been shown to offer excellent LC with minimal late grade >= 2 toxicity rate in a recent multi-institutional phase II study. We underscore that a short course of SBRT offers an expeditious alternative to a long course of chemoradiation, allowing the use of fully intensive systemic therapy. PMID- 27555985 TI - Therapy-Associated Myeloid Dysplasia in a Long-Surviving Patient with Pancreatic Cancer. AB - Pancreatic cancer remains a diagnosis of poor prognosis with a median survival time of four-six months in patients with advanced stage of the disease. Although, with the development of novel chemotherapy agents some patients are able to live a little longer if they respond to therapy. However, long-term complications of chemotherapy or radiotherapy are not known due to the short survival period of patients with pancreatic cancer. We present a case of a 55-year-old-woman who developed therapy-related myelodysplastic syndrome (t-MDS) during a survival of approximately eight years during which she received multiple chemotherapies and radiation therapy. She presented with progressive fatigue and pancytopenia, which led to further work-up and led to the diagnosis of t-MDS. The latency period to developing hematologic abnormalities as well as the presence of the chromosome 5 and 7 abnormalities in this patient are likely consistent with t-MDS and possibly related to the use of chemotherapeutic agents such as oxaliplatin or irinotecan and radiation therapy. PMID- 27555986 TI - Are External Cervical Orthoses Necessary after Anterior Cervical Discectomy and Fusion: A Review of the Literature. AB - INTRODUCTION & BACKGROUND: The use of external cervical orthosis (ECO) after anterior cervical discectomy and fusion (ACDF) varies from physician to physician due to an absence of clear guidelines. Our purpose is to evaluate and present evidence answering the question, "Does ECO after ACDF improve fusion rates?" through a literature review of current evidence for and against ECO after ACDF. REVIEW: A PubMed database search was conducted using specific ECO and ACDF related keywords. Our search yielded a total of 1,267 abstracts and seven relevant articles. In summary, one study provided low quality of evidence results supporting the conclusion that external bracing is not associated with improved fusion rates after ACDF. The remaining six studies provide very low quality of evidence results; two studies concluded that external bracing after cervical procedures is not associated with improved fusion rates, one study concluded that external bracing after cervical procedures is associated with improved fusion rates, and the remaining three studies lacked sufficient evidence to draw an association between external bracing after ACDF and improved fusion rates. CONCLUSION: We recommend against the routine use of ECO after ACDF due to a lack of improved fusion rates associated with external bracing after surgery. PMID- 27555987 TI - Pancreatic Adenocarcinoma Complicated by Sinistral Portal Hypertension. AB - Pancreatic cancer is known for vague symptoms that lead to a delay in diagnosis, and hence most cases are found at an advanced stage. Many complications can happen secondary to pancreatic cancer including diabetes, malabsorption, and deep venous thrombosis. Sinistral (segmental or left-sided) portal hypertension (SPH) refers to portal hypertension confined to the left-sided segment of the portal venous system namely the splenic side, and the most common etiology is splenic vein thrombosis (SVT). We present here a case of a 66-year-old male with advanced pancreatic cancer who died due to bleeding secondary to SVT. We advise physicians caring for these patients to be aware of this complication, which may also be the manifestation of an undiagnosed pancreatic cancer. PMID- 27555988 TI - Comparison of Barriers Against Mammography Screening in Socioeconomically Very Low and Very High Populations. AB - AIM: To compare barriers against mammography screening (MS) in socioeconomically the most and the least developed cities in a developing country, Turkey. METHODS: We compared two population-based survey studies investigating barriers against MS in women aged 40-69 years and living in the lowest socioeconomic status (SES) city (Mus) and the highest SES city (Istanbul/Bahcesehir). RESULTS: In Mus 2,054 and in Bahcesehir 908 women were surveyed. MS rate was higher in Bahcesehir (49% vs. 35%, p<0.001). Being younger than 50 years old and having no insurance were barriers against MS in Mus. Being older than 60 years of age, widowhood, being illiterate, unemployment, a monthly income lower than the hunger threshold and limited insurance coverage were barriers against MS in Bahcesehir. Both in Mus and in Bahcesehir women not reading the daily newspaper and not making annual gynecology visits had lower MS rates. Both in Mus and in Bahcesehir audiovisual media was the most common source of information about breast cancer (BC). Women, who had a chance to be informed about BC by their doctors, had a higher MS rate. Being knowledgeable about BC being the most common cancer in females increased MS rates in both cities, while a false belief of MS exposing to unnecessary radiation decreased MS rates in both cities. CONCLUSION: Both in high and low SES populations more efforts should be given to influence women with low educational level, low-income level, and having no/limited insurance, while designing BC awareness programs. Low SES populations women being in 40-49 years age interval, in high SES populations being in 60-69 years age interval, and widowhood were SES specific barriers and should be taken into consideration. Audiovisual media should be used efficiently to educate women on BC. Physicians from all specialties should not miss the chance to refer their patients to MS. PMID- 27555989 TI - Evaluating the Effectiveness of a Front Windshield Sticker Reminder in Reducing Texting while Driving in Young Adults. AB - Texting while driving is a dangerous activity that is on the rise in the United States (U.S.). Since 2011 there has been a 17% increase in the number of people injured in a motor vehicle crash involving a distracted driver. Bans on the act of texting and driving have already taken place in 46 states in the U.S., but studies have shown that they are ineffective. An unstudied method of reducing texting while driving is sticker reminders. Sticker reminders have already been proven to be an effective intervention in the realm of driver safety; one study found that a "Buckle-Up" dashboard sticker doubled the use of safety belts by front seat passengers. In this study, 104 medical students aged 21 - 29, from the University of Central Florida (UCF) College of Medicine were randomly divided into two groups, an interventional group receiving a "Drive in the Moment" windshield sticker, and a control group not receiving the sticker. Both groups took a pre- and post-survey that recorded self-reported texting and driving frequency. The results showed that the sticker intervention significantly reduced reported rates of sending texts while driving, reading texts while driving, and using social media while driving (p < 0.05). The results of this study suggest that a novel sticker-intervention could potentially serve as a point of attack when addressing the growing and dangerous texting while driving the epidemic. PMID- 27555990 TI - Small Bowel Neuroendocrine Tumors with Inguinal Metastases: A Diagnostic and Therapeutic Dilemma. AB - Small bowel neuroendocrine tumors (NETs) are frequently characterized by a strong propensity to metastasize to the liver, mesentery, and peritoneum. However, only a few extra-abdominal metastatic sites have been reported in the published literature. The present paper implicates that primary small bowel NETs may unusually metastasize to the inguinal lymph nodes. Furthermore, we discuss the formidable diagnostic and therapeutic challenges associated with the metastatic NETs. PMID- 27555991 TI - Myocardial Fatty Foci in Tuberous Sclerosis Complex: Imaging Findings. AB - Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic syndrome. The hallmark of the disease is multiple hamartomatous lesions in multiple organ systems. Common cardiac manifestations of TSC are rhabdomyomas, which are a benign tumor of striated muscle. In some patients with TSC, myocardial fatty foci (MFF) deposition has been described with or without the presence of rhabdomyomas. We present the case of a 24-year-old female with TSC and refractory seizures, who was evaluated with cardiac magnetic resonance (CMR) for an intracardiac right ventricular mass thought to be rhabdomyoma on echocardiography and for multiple areas of myocardial fatty deposition. Myocardial fatty deposition is a common finding in patients at cardiac imaging. In patients with TSC, it is critical that fatty deposits and lipomas are clearly distinguished from rhabdomyoma. CMR is an integral part of characterizing cardiac masses as it has superior soft tissue characterization and a wider field of view compared to echocardiography. A positive correlation has been shown between the number of MFF and the degree of extracardiac tuberous sclerosis (TS) manifestations suggesting that MFF may indicate more severe multiorgan disease in patients with TSC. Cardiac MR is superior to echocardiogram in evaluating and distinguishing intracardiac lipomas and fatty deposits from rhabdomyomas. Published studies have indicated that in patients with TSC, the presence of MFF correlates with the severity of multiorgan disease as was seen in our case. PMID- 27555992 TI - Surgeon Specialty Influences Referral Rate for Osteoporosis Management following Vertebral Compression Fractures. AB - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To evaluate the referral rate for long-term osteoporosis management following vertebral compression fracture treated by different specialties at a single academic institution. METHODS: Patients undergoing vertebral cement augmentation for painful osteoporotic compression fractures from 2009 to 2014 were identified. Medical records were reviewed to determine if the treating surgeon discussed and/or referred the patient for long-term osteoporosis management. Any referral for or mention of medical long-term osteoporosis management was counted as a positive response. Results were statistically analyzed with chi-square test. RESULTS: Two hundred fourteen patients underwent vertebral cement augmentation; 150 met inclusion criteria. Orthopedic surgeons treated 88 patients, neurosurgeons treated 39, and interventional radiology or pain management physicians treated 23. Orthopedic surgeons referred 82% of patients for osteoporosis management, neurosurgeons referred 36%, and interventional radiology/pain management referred 17%. The referral rate was significantly higher for orthopedic surgeons compared with either of the other two groups; there was no significant difference between neurosurgery and interventional radiology/pain management. CONCLUSIONS: Among physicians who treat osteoporotic vertebral compression fractures, orthopedic surgeons more frequently address osteoporosis or refer patients for osteoporosis management compared with neurosurgeons and interventional radiologists or pain management physicians. The results of this study shed light on the disparity in how different specialties approach treatment of osteoporosis in patients with fractures painful enough to require surgery and highlight potential areas for improvement in osteoporosis awareness training. PMID- 27555993 TI - The Application of the Revised Condyle-C1 Interval Method to Diagnose Traumatic Atlanto-occipital Dissociation in Adults. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: Traumatic atlanto-occipital dissociation (AOD) remains a diagnostic challenge, and delay in diagnosis is associated with catastrophic outcomes. Recently, a revised version of the condyl C1 interval (CCI) utilizing parasagittal computed tomography (CT) reconstruction was used successfully with unilateral dislocation of 2.5 mm at the level of that joint diagnostic of AOD. We report the utility of this simple technique in the diagnosis of six patients with AOD. METHODS: Two blinded neurosurgeons assessed CTs of six patients with AOD and 30 patients without AOD. The following methodologies were applied: basion-dens interval (BDI), basion-axial interval (BAI), Lee X-lines, Powers ratio, CCI, and revised CCI. The average sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) as well as the kappa statistic indicating interrater reliability of each method were investigated. RESULTS: The average sensitivity for BDI, BAI, Lee X-lines, Power ratio, CCI, and revised CCI was 0.75, 0.33, 0.67, 0.50, 1.00, and 1.00, respectively. The average specificity was 1.00, 1.00, 0.50, 1.00, 0.94, and 1.00, respectively. The average PPV was 1.00, 1.00, 0.25, 1.00, 0.80, and 1.00, respectively. The average NPV was 0.96, 0.88, 0.89, 0.91, 1.00, and 1.00, respectively, and the kappa statistic was 0.57, 0.25, 0.25, 0.20, 1.00, and 1.00, respectively. CONCLUSION: Based on this study, the revised CCI method is simple yet the most sensitive and reliable technique for the diagnosis of AOD. PMID- 27555994 TI - Comparative Study of Untethering and Spine-Shortening Surgery for Tethered Cord Syndrome in Adults. AB - STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: Although untethering surgery has been a standard treatment in patients with adult tethered cord syndrome (TCS), spine-shortening osteotomy (SSO) has recently been performed as an alternative technique. The purpose of this study was to compare the clinical outcomes of the two procedures for TCS in adults. METHODS: Fourteen patients (37.7 +/- 12.5 years) with TCS were enrolled at 6 hospitals. Their clinical charts, operative records, and follow-up data were reviewed. The categories of tethering lesions were tight terminal filum in 1 patient, lipoma in 5 patients, and lipomyelomeningocele in 8 patients. Eleven patients underwent untethering surgery, and 3 patients underwent SSO surgery. RESULTS: There were no significant differences in age, sex, types of preoperative symptoms, or duration of follow-up between the two groups. The preoperative duration of symptoms was significantly longer (25 +/- 12.4 years) and the percentage of those with prior surgery was higher in the SSO group (66.7%). The preoperative pathology was lipomeningocele in all SSO group and lipoma or tight terminal filum in the untethering group. Cerebrospinal fluid leakage and urinary infection occurred in 1 patient each among those with untethering, and massive intraoperative bleeding occurred in 1 patient with SSO. SSO provided better clinical improvement than untethering surgery (p = 0.003). CONCLUSIONS: Based on this small retrospective case series, SSO appears to provide clinical improvement at least comparable to the untethering procedure, especially in more challenging cases. PMID- 27555995 TI - Inadequate Surgical Decompression in Patients with Cervical Myelopathy: A Retrospective Review. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: We reviewed cases of surgically treated cervical spondylotic myelopathy (CSM) or chronic, degenerative myelopathy of the subaxial cervical spine to study the incidence of inadequate surgical decompression. METHODS: We included all persons treated at our institution after a first surgical decompression for CSM over a 3-year period. Inadequate original surgical decompression was defined as neurologic decline within 12 months postoperatively and ongoing impingement of the spinal cord with <1-mm change in anteroposterior canal dimension from pre- to postoperative magnetic resonance imaging (MRI) leading to revision decompressive surgery. Revisions for other reasons were not counted as inadequate. RESULTS: Of 50 patients, 5 (10%) required revision decompression for neurologic decline and inadequate change in space available for the cord on postoperative imaging; 4 patients declined within the first 6 months and 1 patient at 8 months postoperatively. None of the 5 declined further after posterior revision, but none recovered from the interval loss. All 5 had undergone anterior approaches, for an anterior inadequacy rate of 23% (5 of 22). None of the 28 patients having posterior or combined approach declined at 2 years or had <1-mm change on postoperative MRI. The difference between anterior and posterior approaches was statistically significant (p = 0.018). CONCLUSIONS: The rate of inadequate surgical decompression for CSM was greater than expected in this series and directly associated with an anterior approach. No cases of inadequacy occurred for posterior or combined approaches. Postoperative neuroradiographic imaging such as MRI should be entertained routinely for this entity or at least for anterior-only approaches. PMID- 27555996 TI - Correlation and Reliability of Cervical Sagittal Alignment Parameters between Lateral Cervical Radiograph and Lateral Whole-Body EOS Stereoradiograph. AB - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To evaluate the correlation and reliability of cervical sagittal alignment parameters obtained from lateral cervical radiographs (XRs) compared with lateral whole-body stereoradiographs (SRs). METHODS: We evaluated adults with cervical deformity using both lateral XRs and lateral SRs obtained within 1 week of each other between 2010 and 2014. XR and SR images were measured by two independent spine surgeons using the following sagittal alignment parameters: C2-C7 sagittal Cobb angle (SCA), C2-C7 sagittal vertical axis (SVA), C1-C7 translational distance (C1-7), T1 slope (T1 S), neck tilt (NT), and thoracic inlet angle (TIA). Pearson correlation and paired t test were used for statistical analysis, with intra- and interrater reliability analyzed using intraclass correlation coefficient (ICC). RESULTS: A total of 35 patients were included in the study. We found excellent intrarater reliability for all sagittal alignment parameters in both the XR and SR groups with ICC ranging from 0.799 to 0.994 for XR and 0.791 to 0.995 for SR. Interrater reliability was also excellent for all parameters except NT and TIA, which had fair reliability. We also found excellent correlations between XR and SR measurements for most sagittal alignment parameters; SCA, SVA, and C1-C7 had r > 0.90, and only NT had r < 0.70. There was a significant difference between groups, with SR having lower measurements compared with XR for both SVA (0.68 cm lower, p < 0.001) and C1-C7 (1.02 cm lower, p < 0.001). There were no differences between groups for SCA, T1-S, NT, and TIA. CONCLUSION: Whole-body stereoradiography appears to be a viable alternative for measuring cervical sagittal alignment parameters compared with standard radiography. XR and SR demonstrated excellent correlation for most sagittal alignment parameters except NT. However, SR had significantly lower average SVA and C1-C7 measurements than XR. The lower radiation exposure using single SR has to be weighed against its higher cost compared with XR. PMID- 27555997 TI - Burst C2 Fractures Combined with Traumatic Spondylolisthesis: Can Atlantoaxial Motion Be Preserved? Including Some Technical Tips for Reduction and Fixation. AB - STUDY DESIGN: Retrospective comparative clinical case series. OBJECTIVE: Burst C2 fractures are very rare. Treatment options include conservative treatment or fusion (anterior, posterior, or anterior and posterior). Anterior fusion addresses mainly hangman component. The bursting body usually needs posterior or combined anterior-posterior fusion, but both permanently sacrifice atlantoaxial motion. Can anterior-"first" approach preserve C1-C2 motion and restore function? METHODS: We report nine cases of burst C2 combined with C2-C3 spondylolisthesis and an odontoid fracture. The surgical group included six patients treated initially with an anterior approach, moving to a posterior one when necessary. All were treated with anterior diskectomy fusion using one session and one incision. The halo group included three patients treated conservatively using halo traction followed by rigid collar. Assessments included self-reported, physiologic, and functional measures. Reduction was assessed using Roy-Camille's criteria and improvement of canal compression ratio. Clinical outcome was graded excellent, very good, good, or poor according to pain, range of motion, and work status. RESULTS: Mean follow-up was 44.5 +/- 8.3 (range 36.0 to 62.0) weeks. Results in the surgical group were judged to be excellent in four and good in two. One patient developed atlantoaxial osteoarthritis. Results were good in one patient and poor in two patients in the halo group. Two patients developed atlantoaxial osteoarthritis. All three cases had work limitations. CONCLUSION: A single anterior approach achieved union and preserved C1-C2 motion and function in some cases. Conservative treatment achieved union but failed to achieve good reduction or good clinical outcome in grossly instable fractures. However, we believe that the ideal management is yet to evolve. PMID- 27555998 TI - Relief of Cervicogenic Headaches after Single-Level and Multilevel Anterior Cervical Diskectomy: A 5-Year Post Hoc Analysis. AB - STUDY DESIGN: Prospective study. OBJECTIVE: Because single-level disk arthroplasty or arthrodesis in the lower subaxial spine improves headaches after surgery, we studied whether this effect may be better appreciated after two-level arthroplasty. METHODS: We performed an independent post hoc analysis of two concurrent prospective randomized investigational device exemption trials for cervical spondylosis, one for single-level treatment and the other for two adjacent-level treatments. RESULTS: For the one-level study, baseline mean headache scores significantly improved at 60 months for both the cervical disk arthroplasty (CDA) and anterior cervical diskectomy and fusion (ACDF) groups (p < 0.0001). However, mean improvement in headache scores was not statistically different between the investigational and control groups from 6 months through 60 months. For the two-level study, baseline mean headache scores significantly improved at 60 months for both the CDA and ACDF groups (p < 0.0001). The CDA group demonstrated greater improvement from baseline at all points; this difference was statistically significant at 6, 12, 24, 36, and 48 months but not at 18 and 60 months. CONCLUSION: Both CDA and ACDF at either one or two levels are associated with sustained headache relief from baseline. Patients undergoing two-level arthroplasty had significantly greater improvement in headache at all points except for at 18 and 60 months. This difference in improvement was not observed in patients undergoing single-level arthroplasty. The mechanism of greater headache relief after two-level arthroplasty remains unclear. PMID- 27555999 TI - Postoperative Delayed Cervical Palsies: Understanding the Etiology. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: This study reviews 1,768 consecutive cervical decompressions with or without instrumented fusion to identify patient-specific and procedural risk factors significantly correlated with the development of delayed cervical palsy (DCP). METHODS: Baseline demographic and procedural information was collected from the electronic medical record. Particular attention was devoted to reviewing each chart for recognized risk factors of postsurgical inflammatory neuropathy: autoimmune disease, blood transfusions, diabetes, and smoking. RESULTS: Of 1,669 patients, 56 (3.4%) developed a DCP. Although 71% of the palsies involved C5, 55% of palsies were multimyotomal and 18% were bilateral. Significant risk factors on univariate analysis included age (p = 0.0061, odds ratio [OR] = 1.07, 95% confidence interval [CI] 1.008 to 1.050), posterior instrumented fusion (p < 0.0001, OR = 3.30, 95% CI 1.920 to 5.653), prone versus semisitting/sitting position (p = 0.0036, OR = 3.58, 95% CI 1.451 to 11.881), number of operative levels (p < 0.0001, OR = 1.42, 95% CI 1.247 to 1.605), intraoperative transfusions (p = 0.0231, OR = 2.57, 95% CI 1.152 to 5.132), and nonspecific autoimmune disease (p = 0.0107, OR = 3.83, 95% CI 1.418 to 8.730). On multivariate analysis, number of operative levels (p = 0.0053, OR = 1.27, 95% CI 1.075 to 1.496) and nonspecific autoimmune disease (p = 0.0416, OR 2.95, 95% CI 1.047 to 7.092) remained significant. CONCLUSIONS: Although this study partially supports a mechanical etiology in the pathogenesis of a DCP, we also describe a notable correlation with autoimmune risk factors. Bilateral and multimyotomal involvement provides additional support that some DCPs may result from an inflammatory response and thus an underlying multifactorial etiology for this complication. PMID- 27556000 TI - Management of Giant Calcified Thoracic Disks and Description of the Trench Vertebrectomy Technique. AB - STUDY DESIGN: Case series and review of the literature. OBJECTIVE: To review the management of giant calcified disks in our large cohort and compare with the existing literature. We discuss our surgical technique. METHODS: Twenty-nine cases of herniated thoracic disk between 2000 and 2013 were reviewed. Eighteen patients were identified as having giant calcified thoracic disks, defined as diffusely calcified disks occupying at least 40% of the spinal canal. Demographic data was collected in addition to presentation, imaging findings, operative details, and outcomes using the modified Japanese Orthopaedic Association (mJOA) scale. RESULTS: Giant calcified thoracic disks (GCTDs) are unique clinical entities that require special neurosurgical consideration owing to significant (>=40%) involvement of the spinal canal and compression of the spinal cord, often leading to myelopathy. The median age at diagnosis was 51.2 years (range 37 to 70) with the mean duration of presenting symptoms being 9.9 months (range 2 weeks to 3 years). Seventeen (94.4%) patients presented with at least one sign of myelopathy (hyperreflexia, hypertonia, bladder or bowel dysfunction) with the remaining 1 (5.6%) patient presenting with symptoms in keeping with radiculopathy. Thoracotomy was performed on 17 (94.4%) patients, and 1 (5.6%) patient had a costotransverse approach. Mean follow-up was 19.8 months (range 7 months to 2 years). mJOA score improved in 15 (83.3%) patients. mJOA scores in the other patients remained stable. CONCLUSIONS: GCTDs are difficult neurosurgical challenges owing to their size, degree of spinal cord compression, and consistency. We recommend a trench vertebrectomy via a thoracotomy in their surgical management. This procedure safely allows the identification of normal dura on either side of the compressed segment prior to performing a diskectomy. Excellent fusion rates were achieved with insertion of rib head autograft in the trench. PMID- 27556001 TI - Iliac Crest Bone Graft versus Local Autograft or Allograft for Lumbar Spinal Fusion: A Systematic Review. AB - STUDY DESIGN: Systematic review. OBJECTIVE: To compare the effectiveness and safety between iliac crest bone graft (ICBG) and local autologous bone and allograft in the lumbar spine. METHODS: A systematic search of multiple major medical reference databases identified studies evaluating spinal fusion in patients with degenerative joint disease using ICBG, local autograft, or allograft in the thoracolumbar spine. RESULTS: Six comparative studies met our inclusion criteria. A "low" strength of the overall body of evidence suggested no difference in fusion percentages in the lumbar spine between local autograft and ICBG. We found no difference in fusion percentages based on low evidence comparing allograft with ICBG autograft. There were no differences in pain or functional results comparing local autograft or allograft with ICBG autograft. Donor site pain and hematoma/seroma occurred more frequently in ICBG autograft group for lumbar fusion procedures. There was low evidence around the estimate of patients with donor site pain following ICBG harvesting, ranging from 16.7 to 20%. With respect to revision, low evidence demonstrated no difference between allograft and ICBG autograft. There was no evidence comparing patients receiving allograft with local autograft for fusion, pain, functional, and safety outcomes. CONCLUSION: In the lumbar spine, ICBG, local autograft, and allograft have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes. However, ICBG is associated with an increased risk for donor site related complications. Significant limitations exist in the available literature when comparing ICBG, local autograft, and allograft for lumbar fusion, and thus ICBG versus other fusion methods necessitates further investigation. PMID- 27556002 TI - Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review. AB - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). METHODS: A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. RESULTS: The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. CONCLUSION: Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID- 27556004 TI - Erratum: Adolescent Idiopathic Scoliosis and Pregnancy: An Unsolved Paradigm. AB - [This corrects the article DOI: 10.1055/s-0035-1552987.]. PMID- 27556003 TI - Athletic Population with Spondylolysis: Review of Outcomes following Surgical Repair or Conservative Management. AB - STUDY DESIGN: Narrative review. OBJECTIVE: The study aims to critically review the outcomes associated with the surgical repair or conservative management of spondylolysis in athletes. METHODS: The English literature listed in MEDLINE/PubMed was reviewed to identify related articles using the term "spondylolysis AND athlete." The criteria for studies to be included were management of spondylolysis in athletes, English text, and no year, follow-up, or study design restrictions. The references of the retrieved articles were also evaluated. The primary outcome was time to return to sport. This search yielded 180 citations, and 25 publications were included in the review. RESULTS: Treatment methods were dichotomized as operative and nonoperative. In the nonoperative group, 390 athletes were included. A combination of bracing with physical therapy and restriction of activities was used. Conservative measures allowed athletes to return to sport in 3.7 months (weighted mean). One hundred seventy-four patients were treated surgically. The most common technique was Buck's, using a compression screw (91/174). All authors reported satisfactory outcomes. Time to return to play was 7.9 months (weighted mean). There were insufficient studies with suitably homogenous subgroups to conduct a meta analysis. CONCLUSION: There is no gold standard approach for the management of spondylolysis in the athletic population. The existing literature suggests initial therapy should be a course of conservative management with thoracolumbosacral orthosis brace, physiotherapy, and activity modification. If conservative management fails, surgical intervention should be considered. Two sided clinical studies are needed to determine an optimal pathway for the management of athletes with spondylolysis. PMID- 27556005 TI - Pathological and Topographical Classification of Craniopharyngiomas: A Literature Review. AB - Craniopharyngiomas (CPs) are clinically relevant tumors of the sellar region and are associated with high morbidity and occasional mortality. There are two different subtypes of CPs that differ clinically and pathologically: adamantinomatous CP and papillary CP. The differential diagnosis is still challenging even with developments in preoperative imaging as several tumors of the sellar/parasellar region share a continuum of clinical characteristics and imaging similarities. Several topographical classifications of CPs have been mentioned in literature, but to date, there has not been a consensus on a standard reference classification system and there is need to a develop such a model. PMID- 27556006 TI - Stigma, substance use and sexual risk behaviors among HIV-infected men who have sex with men: A qualitative study. AB - BACKGROUND: Public health HIV-service providers, including Medical Case Managers (case managers) and Disease Intervention Specialists (DIS) have a key role to play in identifying and addressing clients' complex mental health needs and substance use which contribute to sexual risk behaviors, yet their understanding and its consensus with HIV-infected men who have sex with men (MSM) have not been well characterized. METHODS: Together with an AIDS Service Organization and the Connecticut State Department of Public Health in 2011-2012, we conducted a focus group of case managers (n = 14) and interviewed DIS (n = 7) and HIV-infected MSM (n = 17) in Connecticut. We used the constant comparison method, grounded theory, and a community-based participatory approach to guide analysis. RESULTS: We identified three themes characterizing public health HIV-service providers' and MSM's perspectives regarding factors contributing to substance use and sexual risk behaviors in the context of HIV infection: 1) While both MSM and providers described a co-occurrence of HIV, stigma, substance use, and sexual risk behaviors, only MSM identified a causal relationship between these factors; 2) MSM and providers both described varying levels of self-efficacy in readiness to decrease substance use and sexual risk behaviors among MSM; both identified the social network as the key barrier to overcome; 3) Providers described how the co occurrence of HIV, stigma and sexual risk behaviors leads to multi-faceted client needs for which they lacked sufficient training and collaboration. CONCLUSIONS: Provider education, skills-based training, and interventions targeting social networks may decrease sexual risk behaviors among HIV-infected MSM. PMID- 27556007 TI - Addressing ethical challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT). AB - BACKGROUND: The conduct of international collaborative genomics research raises distinct ethical challenges that require special consideration, especially if conducted in settings that are research-naive or resource-limited. Although there is considerable literature on these issues, there is a dearth of literature chronicling approaches taken to address these issues in the field. Additionally no previous ethical guidelines have been developed to support similar research in Trinidad and Tobago. METHODS: A literature review was undertaken to identify strategies used to address common ethical issues relevant to human genetics and genomics research in research-naive or resource-limited settings. Strategies identified were combined with novel approaches to develop a culturally appropriate, multifaceted strategy to address potential challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT). RESULTS: Regarding the protection of study participants, we report a decision to exclude children as participants; the use of a Community Engagement and Sensitization Strategy to increase the genetic literacy of the target population; the involvement of local expertise to ensure cultural sensitivity and to address potential comprehension barriers in informed consent; and an audit of the informed consent process to ensure valid consent. Concerning the regulation of the research, we report on ethics approvals from relevant authorities; a Materials Transfer Agreement to guide sample ownership and export; and a Sample Governance Committee to oversee data use and data access. Finally regarding the protection of the interests of scientists from the host country, we report on capacity building efforts to ensure that local scientists have access to data collected through the project and appropriate recognition of their contributions in future publications. CONCLUSION: This paper outlines an ethical framework for the conduct of population-based genetics and genomics research in Trinidad and Tobago; highlights common issues arising in the field and strategies to address these. PMID- 27556008 TI - RANK and RANK ligand expression in primary human osteosarcoma. AB - Receptor activator of nuclear factor kappa-B ligand (RANKL) is an essential mediator of osteoclast formation, function and survival. In patients with solid tumor metastasis to the bone, targeting the bone microenvironment by inhibition of RANKL using denosumab, a fully human monoclonal antibody (mAb) specific to RANKL, has been demonstrated to prevent tumor-induced osteolysis and subsequent skeletal complications. Recently, a prominent functional role for the RANKL pathway has emerged in the primary bone tumor giant cell tumor of bone (GCTB). Expression of both RANKL and RANK is extremely high in GCTB tumors and denosumab treatment was associated with tumor regression and reduced tumor-associated bone lysis in GCTB patients. In order to address the potential role of the RANKL pathway in another primary bone tumor, this study assessed human RANKL and RANK expression in human primary osteosarcoma (OS) using specific mAbs, validated and optimized for immunohistochemistry (IHC) or flow cytometry. Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79) of samples exhibited>=10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor. PMID- 27556010 TI - Detection of taeniid (Taenia spp., Echinococcus spp.) eggs contaminating vegetables and fruits sold in European markets and the risk for metacestode infections in captive primates. AB - Due to frequent cases of alveolar echinococcosis (AE) in captive primates in Europe, 141 samples of food, which consisting of vegetables and fruits, were investigated for contamination with egg-DNA of taeniids. Each sample consisted of at least 40 heads of lettuce as well as various vegetables and fruits. The samples were purchased at different times of the year: either from September to November (autumn), originating from greenhouses or fields in the Basel region in the North of Switzerland, or in April and May (spring) when fruit and vegetables are sourced from throughout Europe from various wholesalers. Each sample was washed, and the washing water sieved through mesh apertures of 50 MUm and 21 MUm, respectively. The debris, including taeniid eggs, collected on the 21 MUm sieve were investigated by a multiplex PCR-analysis followed by direct sequencing. In 17 (18%) of the 95 samples collected in autumn, taeniid-DNA was detected (Taenia hydatigena in four, Taenia ovis in three, Taenia polyacantha in two and Hydatigera (Taenia) taeniaeformis in five cases). Similarly, in 13 (28%) of the 46 samples collected during spring taeniid-DNA was detected (Echinococcus granulosus s.l. in two, Taenia crassiceps in one, T. hydatigena in two, Taenia multiceps/Taenia serialis in two, Taenia saginata in one and H. taeniaeformis in five cases). Although DNA of Echinococcus multilocularis was not found specifically in this study, the detection of other fox taeniids reveals that vegetables and fruit fed to the primates at the Zoo Basel at different times of the year and from different origin are contaminated with carnivore's faeces and therefore act as a potential source of AE infections. PMID- 27556011 TI - Whole genome sequencing of Mycobacterium tuberculosis SB24 isolated from Sabah, Malaysia. AB - Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis (TB) that causes millions of death every year. We have sequenced the genome of M. tuberculosis isolated from cerebrospinal fluid (CSF) of a patient diagnosed with tuberculous meningitis (TBM). The isolated strain was referred as M. tuberculosis SB24. Genomic DNA of the M. tuberculosis SB24 was extracted and subjected to whole genome sequencing using PacBio platform. The draft genome size of M. tuberculosis SB24 was determined to be 4,452,489 bp with a G + C content of 65.6%. The whole genome shotgun project has been deposited in NCBI SRA under the accession number SRP076503. PMID- 27556012 TI - Microarray analyses for identifying genes conferring resistance to pepper leaf curl virus in chilli pepper (Capsicum spp.). AB - Pepper leaf curl virus (PepLCV) is a serious threat to pepper (Capsicum spp.) production worldwide. Molecular mechanism underlying pepper plants response to PepLCV infection is key to develop PepLCV resistant varieties. In this study, we generated transcriptome profiles of PepLCV resistant genotype (BS-35) and susceptible genotype (IVPBC-535) after artificial viral inoculation using microarray technology and detail experimental procedures and analyses are described. A total of 319 genes differentially expressed between resistant and susceptible genotypes were identified, out of that 234 unique genes were found to be up-regulated > 2-fold in resistant line BS-35 when compared to susceptible, IVPBC-535. The data set we generated has been analyzed to identify genes that are involved in the regulation of resistance against PepLCV. The raw data have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE41131. PMID- 27556009 TI - Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis. AB - Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence. PMID- 27556013 TI - Elements of lentiviral vector design toward gene therapy for treating mucopolysaccharidosis I. AB - Mucopolysaccharidosis type I (MPS I) is a lysosomal disease caused by alpha-l iduronidase (IDUA) deficiency and accumulation of glycosaminoglycans (GAG). Lentiviral vector encoding correct IDUA cDNA could be used for treating MPS I. To optimize the lentiviral vector design, 9 constructs were designed by combinations of various promoters, enhancers, and codon optimization. After in vitro transfection into 293FT cells, 5 constructs achieved the highest IDUA activities (5613 to 7358 nmol/h/mg protein). These 5 candidate vectors were then tested by injection (1 * 10(7) TU/g) into neonatal MPS I mice. After 30 days, one vector, CCEoIDW, achieved the highest IDUA levels: 2.6% of wildtype levels in the brain, 9.9% in the heart, 200% in the liver and 257% in the spleen. CCEoIDW achieved the most significant GAG reduction: down 49% in the brain, 98% in the heart, 100% in the liver and 95% in the spleen. Further, CCEoIDW had the lowest transgene frequency, especially in the gonads (0.03 +/- 0.01 copies/100 cells), reducing the risk of insertional mutagenesis and germ-line transmission. Therefore, CCEoIDW is selected as the optimal lentiviral vector for treating MPS I disease and will be applied in large animal preclinical studies. Further, taken both in vitro and in vivo comparisons together, codon optimization, use of EF-1alpha promoter and woodchuck hepatitis virus posttranscriptional response element (WPRE) could enhance transgene expression. These results provided a better understanding of factors contributing efficient transgene expression in lentiviral gene therapies. PMID- 27556015 TI - A re-usable wave bioreactor for protein production in insect cells. AB - Wave-mixed bioreactors have increasingly replaced stainless steel stirred tank reactors in seed inoculum productions and mammalian cell-based process developments. Pre-sterilized, single-use plastic bags are used for cultivation, eliminating the risk of cross-contamination and cleaning procedures. However, these advantages come with high consumable costs which is the main barrier to more uptakes of the technology by academic institutions. As an academic Core Facility that faces high demand in protein production from insect cells, we have therefore developed a cost-effective alternative to disposable wave bags. In our study we identified: *A re-usable wave shaken polycarbonate bioreactor for protein production in insect cells achieves protein yields comparable to disposable bags.*The advantages of this re-usable bioreactor are low costs, long life cycle, flexible configuration of accessories and convenient handling due to its rigid shape. PMID- 27556016 TI - Brainstem Glioma in Adults. AB - Brainstem gliomas are not nearly as common in adults as they are in children. They are likely the final common consequence not of a single disease process but of several. They can be difficult to diagnose, and are challenging to treat. Clinical studies of this diagnosis are few and generally small. Because of these factors, our understanding of the biology of adult brainstem glioma is incomplete. However, the knowledge base is growing and progress is being made. In this article, we review the current state of knowledge for brainstem glioma in adults and identify key areas for which additional information is required. PMID- 27556017 TI - Minimally invasive prostate cancer detection test using FISH probes. AB - PURPOSE: The ability to test for and detect prostate cancer with minimal invasiveness has the potential to reduce unnecessary prostate biopsies. This study was conducted as part of a clinical investigation for the development of an OligoFISH((r)) probe panel for more accurate detection of prostate cancer. MATERIALS AND METHODS: One hundred eligible male patients undergoing transrectal ultrasound biopsies were enrolled in the study. After undergoing digital rectal examination with pressure, voided urine was collected in sufficient volume to prepare at least two slides using ThinPrep. Probe panels were tested on the slides, and 500 cells were scored when possible. From the 100 patients recruited, 85 had more than 300 cells scored and were included in the clinical performance calculations. RESULTS: Chromosomes Y, 7, 10, 20, 6, 8, 16, and 18 were polysomic in most prostate carcinoma cases. Of these eight chromosomes, chromosomes 7, 16, 18, and 20 were identified as having the highest clinical performance as a fluorescence in situ hybridization test and used to manufacture the fluorescence in situ hybridization probe panels. The OligoFISH((r)) probes performed with 100% analytical specificity. When the OligoFISH((r)) probes were compared with the biopsy results for each individual, the test results highly correlated with positive and negative prostate biopsy pathology findings, supporting their high specificity and accuracy. Probes for chromosomes 7, 16, 18, and 20 showed in the receiver operator characteristics analysis an area under the curve of 0.83, with an accuracy of 81% in predicting the biopsy result. CONCLUSION: This investigation demonstrates the ease of use with high specificity, high predictive value, and accuracy in identifying prostate cancer in voided urine after digital rectal examination with pressure. The test is likely to have positive impact on clinical practice and advance approaches to the detection of prostate cancer. Further evaluation is warranted. PMID- 27556014 TI - The broken "Off" switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance. AB - Aberrant activation of signal transduction pathways can transform a normal cell to a malignant one and can impart survival properties that render cancer cells resistant to therapy. A diverse set of cascades have been implicated in various cancers including those mediated by serine/threonine kinases such RAS, PI3K/AKT, and PKC. Signal transduction is a dynamic process involving both "On" and "Off" switches. Activating mutations of RAS or PI3K can be viewed as the switch being stuck in the "On" position resulting in continued signaling by a survival and/or proliferation pathway. On the other hand, inactivation of protein phosphatases such as the PP2A family can be seen as the defective "Off" switch that similarly can activate these pathways. A problem for therapeutic targeting of PP2A is that the enzyme is a hetero-trimer and thus drug targeting involves complex structures. More importantly, since PP2A isoforms generally act as tumor suppressors one would want to activate these enzymes rather than suppress them. The elucidation of the role of cellular inhibitors like SET and CIP2A in cancer suggests that targeting these proteins can have therapeutic efficacy by mechanisms involving PP2A activation. Furthermore, drugs such as FTY-720 can activate PP2A isoforms directly. This review will cover the current state of knowledge of PP2A role as a tumor suppressor in cancer cells and as a mediator of processes that can impact drug resistance and immune surveillance. PMID- 27556018 TI - Evaluation and management of overactive bladder: strategies for optimizing care. AB - Overactive bladder (OAB) is a common condition affecting millions of men and women worldwide. It is an embarrassing condition with far-reaching consequences. Although many treatment options exist, no single treatment has been proven to be most effective. Often a combination of therapy is required to successfully manage OAB symptoms. In this review, we provide an overview of OAB, including risk factors for development of OAB; keys to diagnosis; therapeutic options including conservative and medical management, as well as treatments for refractory OAB; when to consider referral to a specialist; and resources for clinicians and patients. The aim of this review is to inform clinicians regarding OAB management in order to improve patient counseling and care. PMID- 27556019 TI - Malocclusion and early orthodontic treatment requirements in the mixed dentitions of a population of Nigerian children. AB - INTRODUCTION: The aims of this study were to establish the prevalence of dental features that indicate a need for early intervention and to ascertain the prevalence of different methods of early treatment among a population of Nigerian children in mixed dentition. METHODS: Occlusal relationships were evaluated in 101 children in mixed dentition between the ages of 6 and 12 years who presented at the Orthodontic Unit, Department of Child Dental Health, Lagos University Teaching Hospital over a 2 years period. The need for different modes of early orthodontic treatment was also recorded. RESULTS: Anterior tooth rotations (61.4%) and increased overjet (44.6%) were the most prevalent occlusal anomalies. Others included deep bite (31.7%), reverse overjet (13.9%), and anterior open bite (14.8%). Severe maxillary spacing and crowding were exhibited in 12.0% and 5.0%, respectively. About a third (35.7%) of the subjects presented with crossbite while lip incompetence was observed in 43.6% of the subjects. About 44% of the subjects also presented with various oral habits with digit (15.8%) and lip sucking (9.9%) being the most prevalent. Subjects were recommended for treatment with 2 by 4 fixed orthodontic appliances (22.3%), habit breakers (20.7%), removable orthodontic appliances (16.5%), and extractions (15.7%). CONCLUSIONS: Increased overjet and anterior tooth rotation were the majority of occlusal anomalies seen, which are not only esthetically displeasing but may also cause an increased susceptibility to trauma to these teeth. Treatment options varied from extractions only to the use of appliance therapy. PMID- 27556020 TI - Effects of adhesion promoter on orthodontic bonding in fluorosed teeth: A scanning electron microscopy study. AB - INTRODUCTION: The objectives of the present study were to elucidate the effects of fluorosis in orthodontic bonding and to evaluate the efficiency of an adhesion promoter (Assure Universal Bonding Resin) in bonding to fluorosed teeth. MATERIALS AND METHODS: Extracted premolars were divided into two groups on the basis of Thylstrup and Fejerskov Index. Ten samples from each group were etched and evaluated for etching patterns using scanning electron microscope (SEM). The remaining samples were subdivided into four groups of 20 each on the basis of adhesives used: IA, IIA - Transbond XT and IB, IIB - Transbond XT plus Assure Universal Bonding Resin. Shear bond strength (SBS) was measured after 24 h using the universal testing machine. Adhesive remnant index (ARI) scores were recorded using SEM. Statistical analysis was conducted using a two-way analysis of variance, and Tukey's post hoc test was performed on SBS and ARI scores. RESULTS: Similar etching patterns were observed in both fluorosed and nonfluorosed teeth. No significant differences were found in the SBS values observed in both groups (8.66 +/- 3.19 vs. 8.53 +/- 3.44, P = 1.000). Increase in SBS was observed when Assure Universal Bonding Resin was used. Higher ARI scores were observed when adhesion promoter was used for bonding. CONCLUSIONS: Mild-moderately fluorosed teeth etch in a manner similar to the nonfluorosed teeth. Similar bond strengths were achieved in fluorosed and nonfluorosed teeth when conventional composite was used. Use of adhesion promoter increases the bond strengths in both groups of teeth. PMID- 27556021 TI - A comparative evaluation of skeletal, dental, and soft tissue changes with skeletal anchored and conventional facemask protraction therapy. AB - OBJECTIVE: To cephalometrically evaluate and compare the skeletal, dentoalveolar, and soft tissue changes after maxillary protraction with skeletally anchored and conventional facemask. METHODS: The data for the study were collected from the pre- and post-treatment records of patients of maxillary retrusion treated with skeletally anchored and conventional facemask therapy. Twenty subjects were included in the study and were categorized into two groups, namely skeletal anchored maxillary protraction (SAMP) group with the mean age of 10.10 +/- 1.1 years and conventional facemask maxillary protraction (CFMP) group with the mean age of 9.90 +/- 1.1 years. Pre and post-treatment lateral cephalograms were assessed. RESULTS: The data were analyzed by Mann-Whitney test and Wilcoxon signed-rank test. The mean duration of treatment in SAMP group and CFMP group was 5.8 months and 10 months, respectively. The mean forward displacement of the maxilla (vertical point A) was 3.40 +/- 1.07 mm in SAMP group and 2.80 +/- 0.79 mm in CFMP group. The mandible showed downward and backward rotation in both the groups with more rotation in CFMP group. A significant increase in maxillary incisor inclination was seen in CFMP group as compared to SAMP group. A significant decrease was found in mandibular incisor inclination in both the treatment groups. The soft tissue changes corresponded to underlying skeletal tissue. CONCLUSIONS: SAMP is proven to be a better treatment modality as compared to CFMP for achieving true skeletal changes and minimal dental changes in cases with developing skeletal Class III with maxillary retrusion. PMID- 27556022 TI - Mandibular incisor extraction treatment in Angle's Class I malocclusion with peg shaped maxillary lateral incisors. AB - Accurate diagnosis and treatment planning are essential for obtaining ideal treatment result in cases involving mandibular incisor extraction. This case report describes a 15-year-old female with balanced soft-tissue profile, peg shaped maxillary lateral incisors, and moderate mandibular anterior crowding treated with a mandibular incisor extraction. Ideal overbite and overjet were achieved. "Black triangle" formation was avoided due to the bodily movement of mandibular incisors and the use of uprighting springs for ideal axial inclination of mandibular incisors. A mandibular incisor extraction can be an effective treatment option in carefully selected clinical situations. PMID- 27556023 TI - Long-term stability of conservative orthodontic treatment in a patient with temporomandibular joint disorder. AB - This article reports the orthodontic treatment of a 20-year-old patient with dental crowding and temporomandibular joint disorders (TMDs). The patient presented moderate anterior crowding with a Class I molar relationship and masticatory disturbance in the mandibular position induced by previous splint therapy. Orthodontic treatment with multi-bracket appliance was initiated to correct the anterior crowding in both dental arches, after the extraction of first premolars and third molars, and also to maintain the splint-induced position of the condyles. After 26 months of treatment, an acceptable occlusion was achieved without any TMD symptoms. After 18-month retention, flattening on the right condyle was observed, possibly as an adaptative remodeling. After 16 year retention period, the occlusion was maintained without recurrence of any TMD symptoms, indicating a long-term stability of occlusion and temporomandibular joint (TMJ) components. Our results suggest the possibility of compromised treatment in patients with TMD to achieve a long-term stability in occlusion and TMJ function. PMID- 27556024 TI - Total Synthesis of Putative 11-epi-Lyngbouilloside Aglycon. AB - We report here the total synthesis of 11-epi-lyngbouilloside aglycon. Our strategy features a Boeckman-type esterification followed by a RCM to form the 14 membered ring macrolactone and a late-stage side chain introduction via a Wittig olefination. Overall, the final product was obtained in 20 steps and 2% overall yield starting from commercially available 3-methyl-but-3-enol. Most importantly, the strategy employed is versatile enough to eventually allow us to complete the synthesis of the natural product and irrevocably confirm its structure. PMID- 27556025 TI - The Future Liver Remnant in Patients Undergoing the Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) Maintains the Immunological Components of a Healthy Organ. AB - BACKGROUND AND AIMS: A short-interval, two-stage approach termed associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) increases the number of patients with extensive malignant disease of the liver and a small future liver remnant (FLR) that can undergo liver resection. While this approach results in accelerated liver hypertrophy of the FLR, it remains unknown whether this phenomenon is restricted to liver parenchymal cells. In the current study, we evaluated whether ALPPS alters the immunological composition of the deportalized lobe (DL) and the FLR. METHODS: In this prospective, single-center study, liver tissue from the DL and the FLR were collected intra-operatively from adult patients undergoing ALPPS for their liver metastases. The extent of hypertrophy of the FLR was determined by volumetric helical computed tomography. Flow cytometry and histological analyses were conducted on liver tissues to compare the frequency of several immune cell subsets, and the architecture of the liver parenchyma between both stages of ALPPS. RESULTS: A total of 12 patients completed the study. Histologically, we observed a patchy peri-portal infiltration of lymphocytes within the DL, and a significant widening of the liver cords within the FLR. Within the DL, there was a significantly higher proportion of B cells and CD4(+) T cells as well innate-like lymphocytes, namely mucosa-associated invariant T (MAIT) cells and natural killer T (NKT) cells following ALPPS. In contrast, the frequency of all evaluated immune cell types remained relatively constant in the FLR. CONCLUSION: Our results provide the first description of the immunological composition of the human liver following ALPPS. We show that following the ALPPS procedure, while the immune composition of the FLR remains relatively unchanged, there is a moderate increase in several immune cell populations in DL. Overall, our results support the continued utilization of the ALPPS procedure. PMID- 27556026 TI - Simulation-Based Training - Evaluation of the Course Concept "Laparoscopic Surgery Curriculum" by the Participants. AB - INTRODUCTION: The learning curve in minimally invasive surgery is much longer than in open surgery. This is thought to be due to the higher demands made on the surgeon's skills. Therefore, the question raised at the outset of training in laparoscopic surgery is how such skills can be acquired by undergoing training outside the bounds of clinical activities to try to shorten the learning curve. Simulation-based training courses are one such model. METHODS: In 2011, the surgery societies of Germany adopted the "laparoscopic surgery curriculum" as a recommendation for the learning content of systematic training courses for laparoscopic surgery. The curricular structure provides for four 2-day training courses. These courses offer an interrelated content, with each course focusing additionally on specific topics of laparoscopic surgery based on live operations, lectures, and exercises carried out on bio simulators. RESULTS: Between 1st January, 2012 and 31st March, 2016, a total of 36 training courses were conducted at the Vivantes Endoscopic Training Center in accordance with the "laparoscopic surgery curriculum." The training courses were attended by a total of 741 young surgeons and were evaluated as good to very good during continuous evaluation by the participants. CONCLUSION: Training courses based on the "laparoscopic surgery curriculum" for acquiring skills in laparoscopy are taken up and positively evaluated by young surgeons. PMID- 27556028 TI - Screening of Drugs Inhibiting In vitro Oligomerization of Cu/Zn-Superoxide Dismutase with a Mutation Causing Amyotrophic Lateral Sclerosis. AB - Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS). A major pathological hallmark of this disease is abnormal accumulation of mutant SOD1 oligomers in the affected spinal motor neurons. While no effective therapeutics for SOD1-ALS is currently available, SOD1 oligomerization will be a good target for developing cures of this disease. Recently, we have reproduced the formation of SOD1 oligomers abnormally cross-linked via disulfide bonds in a test tube. Using our in vitro model of SOD1 oligomerization, therefore, we screened 640 FDA approved drugs for inhibiting the oligomerization of SOD1 proteins, and three effective classes of chemical compounds were identified. Those hit compounds will provide valuable information on the chemical structures for developing a novel drug candidate suppressing the abnormal oligomerization of mutant SOD1 and possibly curing the disease. PMID- 27556027 TI - Post-translational Serine/Threonine Phosphorylation and Lysine Acetylation: A Novel Regulatory Aspect of the Global Nitrogen Response Regulator GlnR in S. coelicolor M145. AB - Soil-dwelling Streptomyces bacteria such as S.coelicolor have to constantly adapt to the nitrogen (N) availability in their habitat. Thus, strict transcriptional and post-translational control of the N-assimilation is fundamental for survival of this species. GlnR is a global response regulator that controls transcription of the genes related to the N-assimilation in S. coelicolor and other members of the Actinomycetales. GlnR represents an atypical orphan response regulator that is not activated by the phosphorylation of the conserved aspartate residue (Asp 50). We have applied transcriptional analysis, LC-MS/MS analysis and electrophoretic mobility shift assays (EMSAs) to understand the regulation of GlnR in S. coelicolor M145. The expression of glnR and GlnR-target genes was revisited under four different N-defined conditions and a complex N-rich condition. Although, the expression of selected GlnR-target genes was strongly responsive to changing N-concentrations, the glnR expression itself was independent of the N-availability. Using LC-MS/MSanalysis we demonstrated that GlnR was post-translationally modified. The post-translational modifications of GlnR comprise phosphorylation of the serine/threonine residues and acetylation of lysine residues. In the complex N-rich medium GlnR was phosphorylated on six serine/threonine residues and acetylated on one lysine residue. Under defined N excess conditions only two phosphorylated residues were detected whereas under defined N-limiting conditions no phosphorylation was observed. GlnR phosphorylation is thus clearly correlated with N-rich conditions. Furthermore, GlnR was acetylated on four lysine residues independently of the N-concentration in the defined media and on only one lysine residue in the complex N-rich medium. Using EMSAs we demonstrated that phosphorylation inhibited the binding of GlnR to its targets genes, whereas acetylation had little influence on the formation of GlnR-DNA complex. This study clearly demonstrated that GlnR DNA-binding affinity is modulated by post-translational modifications in response to changing N conditions in order to elicit a proper transcriptional response to the latter. PMID- 27556029 TI - Beneficial Effect of Short Pretransplant Period of Hypothermic Pulsatile Perfusion of the Warm-Ischemic Kidney after Cold Storage: Experimental Study. AB - Warm ischemia (WI) produces a significant deleterious effect in potential kidney grafts. Hypothermic machine perfusion (HMP) seems to improve immediate graft function after transplant. Our aim was to analyze the effect of short pretransplant periods of pulsatile HMP on histology and renal injury in warm ischemic kidneys. Twelve minipigs were used. WI was achieved in the right kidney by applying a vascular clamp for 45 min. After nephrectomy, autotransplant was performed following one of two strategies: cold storage of the kidneys or cold storage combined with perfusion in pulsatile HMP. The graft was removed early to study renal morphology, inflammation (fibrosis), and apoptosis. Proinflammatory activity and fibrosis were less pronounced after cold storage of the kidneys with HMP than after cold storage only. The use of HMP also decreased apoptosis compared with cold storage only. The detrimental effects on cells of an initial and prolonged period of WI seem to improve with a preservation protocol that includes a short period of pulsatile HMP after cold storage and immediately before the transplant, in comparison with cold storage only. PMID- 27556030 TI - Diagnostic Potential of Evaluation of SDF-1alpha and sRAGE Levels in Threatened Premature Labor. AB - Preterm birth remains the most prevalent cause of neonatal morbidity. This study aimed to evaluate the diagnostic value of SDF-1alpha, resistin, secretory RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) in preterm labor. A total of 211 pregnant women participated in the study. Group A contained 72 women between 22 and 36 weeks of gestation, with premature labor, who finally had preterm birth. Group B contained 66 women in labor between 37 and 41 weeks of gestation. Women in group A had lower SDF-1alpha and sRAGE levels than those in group B. Moreover, in group A, SDF-1alpha and sRAGE levels were correlated with the latency period from the occurrence of premature labor symptoms until delivery. Sensitivity and specificity of studied parameters for prediction of preterm birth were 95% and 40% for SDF-1alpha and 51.3% and 93.5% for sRAGE, respectively. The prognostic value of plasma SDF-1alpha and sRAGE levels was comparable with that of cervical length ultrasound measurement and serum C-reactive protein levels. We conclude that SDF-1alpha and sRAGE appear to play a major role in the diagnosis of preterm birth and its evaluation could be convenient and useful for predicting preterm birth. PMID- 27556031 TI - Air Pollutants, Climate, and the Prevalence of Pediatric Asthma in Urban Areas of China. AB - Background. Prevalence of childhood asthma varies significantly among regions, while its reasons are not clear yet with only a few studies reporting relevant causes for this variation. Objective. To investigate the potential role of city average levels of air pollutants and climatic factors in order to distinguish differences in asthma prevalence in China and explain their reasons. Methods. Data pertaining to 10,777 asthmatic patients were obtained from the third nationwide survey of childhood asthma in China's urban areas. Annual mean concentrations of air pollutants and other climatic factors were obtained for the same period from several government departments. Data analysis was implemented with descriptive statistics, Pearson correlation coefficient, and multiple regression analysis. Results. Pearson correlation analysis showed that the situation of childhood asthma was strongly linked with SO2, relative humidity, and hours of sunshine (p < 0.05). Multiple regression analysis indicated that, among the predictor variables in the final step, SO2 was found to be the most powerful predictor variable amongst all (beta = -19.572, p < 0.05). Furthermore, results had shown that hours of sunshine (beta = -0.014, p < 0.05) was a significant component summary predictor variable. Conclusion. The findings of this study do not suggest that air pollutants or climate, at least in terms of children, plays a major role in explaining regional differences in asthma prevalence in China. PMID- 27556033 TI - Avian Mycobacteriosis: Still Existing Threat to Humans. AB - The nontuberculous mycobacteria are typically environmental organisms residing in soil and water. These microorganisms can cause a wide range of clinical diseases; pulmonary disease is most frequent, followed by lymphadenitis in children, skin and soft tissue disease, and rare extra pulmonary or disseminated infections. Mycobacterium avium complex is the second most common cause of pulmonary mycobacterioses after M. tuberculosis. This review covers the clinical and laboratory diagnosis of infection caused by the members of this complex and particularities for the treatment of different disease types and patient populations. PMID- 27556034 TI - Enhancing the Feasibility of Microcystis aeruginosa as a Feedstock for Bioethanol Production under the Influence of Various Factors. AB - Microcystis aeruginosa, a freshwater microalga, is capable of producing and accumulating different types of sugars in its biomass which make it a good feedstock for bioethanol production. Present study aims to investigate the effect of different factors increasing growth rate and carbohydrates productivity of M. aeruginosa. MF media (modified BG11 media) and additional ingredients such as aminolevulinic acid (2 mM), lysine (2.28 mM), alanine (1 mM), and Naphthalene acetic acid (1 mM) as cytokine promoted M. aeruginosa growth and sugar contents. Salmonella showed growth-assisting effect on M. aeruginosa. Enhanced growth rate and carbohydrates contents were observed in M. aeruginosa culture grown at 25 degrees C under red LED light of 90 MUmolm(-2)s(-1) intensity. More greenish and carbohydrates rich M. aeruginosa biomass was prepared (final OD660 nm = 2.21 and sugar contents 10.39 mM/mL) as compared to control (maximum OD660 nm = 1.4 and sugar contents 3 mM/mL). The final algae biomass was converted to algae juice through a specific pretreatment method. The resulted algae Juice was used as a substrate in fermentation process. Highest yield of bioethanol (50 mM/mL) was detected when Brettanomyces custersainus, Saccharomyces cerevisiae, and Pichia stipitis were used in combinations for fermentation process as compared to their individual fermentation. The results indicated the influence of different factors on the growth rate and carbohydrates productivity of M. aeruginosa and its feasibility as a feedstock for fermentative ethanol production. PMID- 27556035 TI - Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock. AB - Objectives. The peroxisome proliferator-activated receptor gamma (PPARgamma) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARgamma plays an important role in maraviroc-mediated lung protection following trauma-hemorrhage. Methods. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35 40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARgamma inhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n = 8 rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey's testing were used for statistical analysis. Results. Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1beta levels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury. Conclusion. These results suggest that PPARgamma might play a key role in maraviroc-mediated lung protection following trauma hemorrhage. PMID- 27556036 TI - Radiation Exposure to Staff in Intensive Care Unit with Portable CT Scanner. AB - Background. Bedside radiological procedures pose a risk of radiation exposure to ICU staff. The perception of risk may increase the degree of caution among the health care staff and raise new barriers preventing patients from obtaining prompt care. Objective. The aim of this study was to estimate the annual cumulative radiation dose to individual ICU staff. Methods. In this prospective study, forty subjects were required to wear thermoluminescent dosimeter badges during their working hours. The badges were analyzed to determine the exposure after 3 months. Results. A total of 802 radiological procedures were completed at bedside during the study period. The estimated annual dosage to doctors and nurses on average was 0.99 mSv and 0.88 mSv (p < 0.001), respectively. Residents were subjected to the highest radiation exposure (1.04 mSv per year, p = 0.002). The radiation dose was correlated with day shift working hours (r = 0.426; p = 0.006) and length of service (r = -0.403; p < 0.01). Conclusions. With standard precautions, bedside radiological procedures-including portable CT scans-do not expose ICU staff to high dose of ionizing radiation. The level of radiation exposure is related to the daytime working hours and length of service. PMID- 27556032 TI - Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery. AB - Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID- 27556037 TI - The Role of RhoJ in Endothelial Cell Biology and Tumor Pathology. AB - Background. RhoJ, an endothelially expressed member of Cdc42 (cell division cycle 42) subfamily of Rho GTPase, plays an important role in endocytic pathway, adipocyte differentiation, endothelial motility, tube formation, and focal adhesion. RhoJ is a selective and effective therapeutic target in tumor tissues or retinopathy. Methods. A systematic review was related to "small Rho GTPase" or "RhoJ" with "endothelial motility, tube formation and focal adhesion" and "tumor therapy". This led to many cross-references involving RhoJ and these data have been incorporated into the following study. Results. We have grouped the role of RhoJ according to three main effects: RhoJ regulates endocytic pathway and adipocyte differentiation in early studies, and RhoJ shows an important role in endothelial cell biology; furthermore, RhoJ blockade serves as a target in tumor vasculature and enhances the effects of anticancer drug. Conclusions. More research is necessary to understand the role of RhoJ in many aspects, on the basis of current knowledge of the role of RhoJ blockade in tumor vessels, there are opportunities for the therapy of tumor, and RhoJ is expressed outside tumour vasculature and is involved in wound healing. Taking advantage of the opportunities could result in a development in tumor therapy. PMID- 27556038 TI - Targeting Lung Cancer Stem Cells with Antipsychological Drug Thioridazine. AB - Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells. PMID- 27556039 TI - PET Evidence of the Effect of Donepezil on Cognitive Performance in an Animal Model of Chemobrain. AB - A considerable number of patients with breast cancer complain of cognitive impairment after chemotherapy. In this study, we showed that donepezil enhanced memory function and increased brain glucose metabolism in a rat model of cognitive impairment after chemotherapy using behavioral analysis and positron emission tomography (PET). We found that chemotherapy affected spatial learning ability, reference memory, and working memory and that donepezil improved these cognitive impairments. According to PET analysis, chemotherapy reduced glucose metabolism in the medial prefrontal cortex and hippocampus, and donepezil increased glucose metabolism in the bilateral frontal lobe, parietal lobe, and hippocampus. Reduced glucose metabolism was more prominent after treatment with doxorubicin than cyclophosphamide. Our results demonstrated the neural mechanisms for cognitive impairment after chemotherapy and show that cognition was improved after donepezil intervention using both behavioral and imaging methods. Our results suggested that donepezil can be employed clinically for the treatment of cognitive deficits after chemotherapy. PMID- 27556040 TI - Effect of Anti-TNF Antibodies on Clinical Response in Rheumatoid Arthritis Patients: A Meta-Analysis. AB - Background. Antitumor necrosis factor (anti-TNF) drugs have been applied for rheumatoid arthritis (RA) treatment; however, patients having anti-drug antibodies (ADAbs) do not benefit from these drugs. The meta-analysis aims to comprehensively assess the relationship between ADAb positive (ADAb+) and anti TNF response in RA patients. Methods. Observational studies comparing different clinical response between ADAb+ and ADAb negative groups were included. Odds ratio (OR) with its corresponding 95% confidence interval (CI) was used as effect size. Subgroup analyses stratified by TNF inhibitor types and assay methods for ADAb detection were performed. Results. Totally, 10 eligible studies containing 1806 subjects were included. ADAb+ was significantly associated with reduced anti TNF response to RA at all the time points after follow-up (P < 0.001). Subgroup analysis also supported this significant association (P < 0.05), except for enzyme-linked immunosorbent assay (ELISA) group at 3 months, infliximab (INF) and enzyme-linked immunosorbent assay (ELISA) groups at 6 months, and Immunological Multi-Parameter Chip Technology (IMPACT) group at 12 months. Conclusion. ADAb+ was significantly associated with reduced clinical response in RA patients, and other alternatives should be considered in RA patients presenting ADAb+. PMID- 27556041 TI - National Survey of Workplaces Handling and Manufacturing Nanomaterials, Exposure to and Health Effects of Nanomaterials, and Evaluation of Nanomaterial Safety Data Sheets. AB - A national survey on workplace environment nanomaterial handling and manufacturing was conducted in 2014. Workplaces relevant to nanomaterials were in the order of TiO2 (91), SiO2 (88), carbon black (84), Ag (35), Al2O3 (35), ZnO (34), Pb (33), and CeO2 (31). The survey results indicated that the number of workplaces handling or manufacturing nanomaterials was 340 (0.27% of total 126,846) workplaces. The number of nanomaterials used and products was 546 (1.60 per company) and 583 (1.71 per company), respectively. For most workplaces, the results on exposure to hazardous particulate materials, including nanomaterials, were below current OELs, yet a few workplaces were above the action level. As regards the health status of workers, 9 workers were diagnosed with a suspected respiratory occupational disease, where 7 were recommended for regular follow-up health monitoring. 125 safety data sheets (SDSs) were collected from the nanomaterial-relevant workplaces and evaluated for their completeness and reliability. Only 4 CNT SDSs (3.2%) included the term nanomaterial, while most nanomaterial SDSs were not regularly updated and lacked hazard information. When taken together, the current analysis provides valuable national-level information on the exposure and health status of workers that can guide the next policy steps for nanomaterial management in the workplace. PMID- 27556042 TI - Microbial Production of Short Chain Fatty Acids from Lignocellulosic Biomass: Current Processes and Market. AB - Biological production of organic acids from conversion of biomass derivatives has received increased attention among scientists and engineers and in business because of the attractive properties such as renewability, sustainability, degradability, and versatility. The aim of the present review is to summarize recent research and development of short chain fatty acids production by anaerobic fermentation of nonfood biomass and to evaluate the status and outlook for a sustainable industrial production of such biochemicals. Volatile fatty acids (VFAs) such as acetic acid, propionic acid, and butyric acid have many industrial applications and are currently of global economic interest. The focus is mainly on the utilization of pretreated lignocellulosic plant biomass as substrate (the carbohydrate route) and development of the bacteria and processes that lead to a high and economically feasible production of VFA. The current and developing market for VFA is analyzed focusing on production, prices, and forecasts along with a presentation of the biotechnology companies operating in the market for sustainable biochemicals. Finally, perspectives on taking sustainable product of biochemicals from promise to market introduction are reviewed. PMID- 27556043 TI - HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases. AB - Histone deacetylase (HDAC) inhibitors are powerful epigenetic regulators that have enormous therapeutic potential and have pleiotropic effects at the cellular and systemic levels. To date, HDAC inhibitors are used clinically for a wide variety of disorders ranging from hematopoietic malignancies to psychiatric disorders, are known to have anti-inflammatory properties, and are in clinical trials for several other diseases. In addition to influencing gene expression, HDAC enzymes also function as part of large, multisubunit complexes which have many nonhistone targets, alter signaling at the cellular and systemic levels, and result in divergent and cell-type specific effects. Thus, the effects of HDAC inhibitor treatment are too intricate to completely understand with current knowledge but the ability of HDAC inhibitors to modulate the immune system presents intriguing therapeutic possibilities. This review will explore the complexity of HDAC inhibitor treatment at the cellular and systemic levels and suggest strategies for effective use of HDAC inhibitors in biomedical research, focusing on the ability of HDAC inhibitors to modulate the immune system. The possibility of combining the documented anticancer effects and newly emerging immunomodulatory effects of HDAC inhibitors represents a promising new combinatorial therapeutic approach for HDAC inhibitor treatments. PMID- 27556044 TI - The Expression of Osteopontin and Wnt5a in Articular Cartilage of Patients with Knee Osteoarthritis and Its Correlation with Disease Severity. AB - Objectives. This study is undertaken to investigate the relation between osteopontin (OPN) and Wnt5a expression in the progression and pathogenesis of osteoarthritis (OA). Methods. 50 cartilage tissues from knee OA patients and normal controls were divided into four groups of severe, moderate, minor, and normal lesions based on the modified grading system of Mankin. Immunohistochemistry and real-time PCR were utilized to analyze the OPN and Wnt5a expression in articular cartilage. Besides, the relations between OPN and Wnt5a expression and the severity of OA were explored. Results. OPN and Wnt5a could be identified in four groups' tissues. Amongst the groups, the intercomparisons of OPN expression levels showed statistical differences (P < 0.01). Besides, the intercomparisons of Wnt5a expression degrees showed statistical differences (P < 0.05), except that between the minor and normal groups (P > 0.05). The scores of Mankin were demonstrated to relate to OPN expression (r = -0.847, P < 0.01) and Wnt5a expression in every group (r = -0.843, P < 0.01). Also, a positive correlation can be observed between the OPN and Wnt5a expression (r = 0.769, P < 0.01). Conclusion. In articular cartilage, the expressions of OPN and Wnt5a are positively related to progressive damage of knee OA joint. The correlation between Wnt5a and OPN might be important to the progression and pathogenesis of knee OA. PMID- 27556046 TI - Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System. AB - Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction. PMID- 27556047 TI - PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells. AB - Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD 1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance. We first observe that the UVB-iDC-induced alloantigen-specific tolerance can be maintained for over 6 weeks. Supporting this, at 6 weeks after tolerance induction completion, alloantigen-specific tolerance is still able to be transferred to syngeneic naive mice through adoptive transfer of CD4+ T cells. Furthermore, skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. Further studies show that PD-1/PD-L1 interaction is essential for maintaining the induced tolerance as blockade of PD-1/PD-L1 by anti PD-L1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. Importantly, we show that PD-1/PD-L1 interaction in tolerant mice is also essential for controlling alloantigen-responding T cells, which have never experienced alloantigens. The above findings suggest that PD 1/PD-L1 plays a crucial role in maintaining immune tolerance induced by UVB-iDCs, as well as in actively controlling effector T cells specific to alloantigens. PMID- 27556048 TI - Emerging Technologies and Generic Assays for the Detection of Anti-Drug Antibodies. AB - Anti-drug antibodies induced by biologic therapeutics often impact drug pharmacokinetics, pharmacodynamics response, clinical efficacy, and patient safety. It is critical to assess the immunogenicity risk of potential biotherapeutics in producing neutralizing and nonneutralizing anti-drug antibodies, especially in clinical phases of drug development. Different assay methodologies have been used to detect all anti-drug antibodies, including ELISA, radioimmunoassay, surface plasmon resonance, and electrochemiluminescence-based technologies. The most commonly used method is a bridging assay, performed in an ELISA or on the Meso Scale Discovery platform. In this report, we aim to review the emerging new assay technologies that can complement or address challenges associated with the bridging assay format in screening and confirmation of ADAs. We also summarize generic anti-drug antibody assays that do not require drug specific reagents for nonclinical studies. These generic assays significantly reduce assay development efforts and, therefore, shorten the assay readiness timeline. PMID- 27556045 TI - Zebrafish: A Versatile Animal Model for Fertility Research. AB - The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research. PMID- 27556050 TI - SEC Based Method for Size Determination of Immune Complexes of Therapeutic Antibodies in Animal Matrix. AB - Therapeutic monoclonal antibodies (mAbs) represent a milestone in pharmacological development. Their superiority is based on the combination of high specificity, low toxicity, and long half-life that characterizes biologics. If biologics have Achilles' heel, it is their potential immunogenicity. To better understand the impact of the size of immune complexes of mAbs on anti-drug antibody (ADA) dependent adverse reactions in Macaca fascicularis, we developed an efficient high-throughput size exclusion chromatography- (SEC-) based methodology that enables analysis of the size, size distribution, and ratio of free and ADA complexed mAb in serum allowing for assessment of formation and clearance of circulating ADA-mAb immune complexes (CIC). PMID- 27556049 TI - Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-alpha and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1beta in plasma and IL 1beta mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX. PMID- 27556051 TI - The Effect of G-ORS Along With Rice Soup in the Treatment of Acute Diarrhea in Children: A Single-Blind Randomized Controlled Trial. AB - BACKGROUND: The world health organization guidelines for treatment of diarrhea in children emphasize on continued feeding together with prescription of oral rehydration solution (ORS) and supplementary zinc therapy. However, conflicting viewpoints exist regarding the optimal diet and dietary ingredients for children with diarrhea. Moreover, few studies have investigated the effect of rice soup along with ORS in the treatment of this disease. OBJECTIVES: This study aimed to explore effects of simultaneous taking of glucose oral rehydration solution (G ORS) and rice soup in the treatment of acute diarrhea in 8 to 24-month-old children. PATIENTS AND METHODS: This single-blind controlled clinical trial was conducted in the pediatric ward of 22nd of Bahman hospital, Gonabad, Iran between June 2013 and February 2014. Forty children aged 8-24 months with acute diarrhea were randomly assigned into an intervention group (G-ORS plus rice soup group) comprising 20 babies and a control group (G-ORS) of 20 children based on balanced blocking randomization. The variables under investigation were diarrhea duration, patient hospitalization, need for intravenous (IV) fluids and stool output frequency. Data was analyzed using independent samples t and chi-square test. RESULTS: At the end of study, the time for treating acute watery diarrhea in the intervention and control groups were 21.10 +/- 8.81 and 34.55 +/- 5.82 hours (P < 0.001) and hospital stay were 34.05 +/- 6.62 and 40.20 +/- 6.32 hours (P = 0.005). Moreover, stool output frequency were 4.20 +/- 0.95 and 8.00 +/- 1.37 (P < 0.001) in the first 24 hours, and 2.18 +/- 0.60 and 2.80 +/- 0.76 (P = 0.03) in the second 24 hours of treatment in intervention and control groups, respectively. CONCLUSIONS: Rice soup regimen was highly effective and inexpensive in the treatment of acute diarrhea in children. Thus, in addition to the common treatment by G-ORS, rice soup can be consumed simultaneously with G-ORS. PMID- 27556052 TI - The Effects of Pregnancy-Adaptation Training on Maternal-Fetal Attachment and Adaptation in Pregnant Women With a History of Baby Loss. AB - BACKGROUND: Studies have shown that educating mothers can improve their adaptation to pregnancy and motherhood roles. There are also studies that have investigated the effects of certain interventions on maternal-fetal attachment. However, studies on the effects of maternal adaptation training on maternal-fetal attachment in mothers with a history of fetal or baby loss are rare. OBJECTIVES: The aim of this study was to determine the effects of a pregnancy adaptation training package on maternal-fetal attachment in pregnant women with a history of baby loss. PATIENTS AND METHODS: This quasi-experimental study was conducted on 60 pregnant women with previous fetal or neonatal death in 2014. The women were randomly divided into an experimental group (n = 30) and a control group (n = 30). The pregnant women in the experimental group received routine prenatal education in addition to four sessions of a pregnancy adaption training package. The control group received only routine prenatal education. The data were collected using a demographic questionnaire, Cranley's maternal-fetal attachment scale, and a prenatal self-evaluation questionnaire at the beginning and at the end of the study. The data analysis was conducted using the Mann-Whitney U, Wilcoxon, chi-square, Fisher's exact, and spearman correlation coefficient tests. RESULTS: Before the intervention, there were no statistically significant differences between the study and control groups in terms of maternal-fetal attachment (P = 0.280) and adaptation to pregnancy (P = 0.883). However, following the intervention, the mean score of the maternal-fetal attachment was significantly higher in the experimental group, when compared with the control (77.57 +/- 7.23 vs. 61.53 +/- 2.62; P = 0.001). In addition, the mean post intervention adaptation to pregnancy score was significantly lower in the experimental group than in the control group (118.89 +/- 8.12 vs. 126.38 +/- 4.17; P = 0.001). CONCLUSIONS: The pregnancy adaptation training package increased the adaptation and maternal-fetal attachment scores in pregnant women with a history of baby loss. PMID- 27556053 TI - Evaluation of Mackey Childbirth Satisfaction Rating Scale in Iran: What Are the Psychometric Properties? AB - BACKGROUND: With the integration of the evaluation of patient satisfaction in the overall assessment of healthcare services, authorities can be assured about the alignment of these services with patient needs and the suitability of care provided at the local level. OBJECTIVES: This study was conducted in 2013 in Zahedan, Iran, in order to assess the psychometric properties of the Iranian version of the mackey childbirth satisfaction rating scale (MCSRS). PATIENTS AND METHODS: For this study, a methodological design was used. After translating the MCSRS and confirming its initial validity, the questionnaires were distributed among women with uncomplicated pregnancies and no prior history of cesarean section. The participants had given birth to healthy, full-term, singletons (with cephalic presentation) via normal vaginal delivery at hospitals within the past six months. Cronbach's alpha and test-retest (via the intraclass correlation coefficient) were applied to analyze the internal consistency and reliability of the scale. Moreover, the validity of the scale was tested via exploratory factor analysis, confirmatory factor analysis, and convergent validity. RESULTS: The MCSRS consists of six subscales. Through the process of validation, two partner related items ("partner" subscale) of the scale were excluded due to cultural barriers and hospital policies. Cronbach's alpha for the total scale was 0.78. It ranged between 0.70 and 0.86 for five subscales, and was 0.31 for the "baby" subscale. Factor analysis confirmed the subscales of "nurse," "physician," and "baby," which were identified in the original scale. However, in the translated version, the "self" subscale was divided into two separate dimensions. The six subscales explained 70.37% of the variance. Confirmatory factor analysis indicated a good fitness for the new model. Convergent validity showed a significant correlation between the MCSRS and the SERVQUAL scale (r = 0.72, P < 0.001). Moreover, the Farsi version of the MCSRS showed excellent repeatability (r = 0.81 - 0.96 for individual subscales and r = 0.96 for the entire scale). CONCLUSIONS: The study findings indicated the Farsi version of the MCSRS is a reliable and valid instrument. However, according to the reliability assessment and factor analysis, the "baby" and "self" subscales need further revisions. PMID- 27556054 TI - Skills Required for Nursing Career Advancement: A Qualitative Study. AB - BACKGROUND: Nurses require certain skills for progression in their field. Identifying these skills can provide the context for nursing career advancement. OBJECTIVES: This study aimed to identify the skills needed for nurses' career advancement. MATERIALS AND METHODS: A qualitative approach using content analysis was adopted to study a purposive sample of eighteen nurses working in teaching hospitals affiliated with the Qazvin, Shahid Beheshti, and Iran Universities of Medical Sciences. The data were collected through semi-structured interviews, and analyzed using conventional content analysis. RESULTS: The three themes extracted from the data included interpersonal capabilities, competency for career success, and personal capacities. The results showed that acquiring a variety of skills is essential for career advancement. CONCLUSIONS: The findings showed that personal, interpersonal, and functional skills can facilitate nurses' career advancement. The effects of these skills on career advancement depend on a variety of conditions that require further studies. PMID- 27556055 TI - Self-Concept in Mothers of Educable Mentally Retarded Children. PMID- 27556056 TI - The Quality of Pre-hospital Circulatory Management in Patients With Multiple Trauma Referred to the Trauma Center of Shahid Beheshti Hospital in Kashan, Iran, in the First Six Months of 2013. AB - BACKGROUND: Circulatory management is a critical issue in pre-hospital transportation phase of multiple trauma patients. However, the quality of this important care did not receive enough attention. OBJECTIVES: The aim of this study was to investigate the quality of pre-hospital circulatory management in patients with multiple trauma. PATIENTS AND METHODS: This was a cross-sectional study conducted in 2013. The study population consisted of all patients with multiple trauma who had been transferred by emergency medical services (EMS) to the central trauma department in Kashan Shahid Beheshti medical center, Kashan, Iran. We recruited a convenience sample of 400 patients with multiple trauma. Data were collected using the circulatory assessment questionnaire and controlling hemorrhage (CAQCH) that were designed by the researchers and were described by using frequency tabulations, central tendency measures, and variability indices. The chi-square test was used to analyze the data. RESULTS: The study sample consisted of 263 males (75.2%); 57.75% had lower levels of education and 28.75% were workers. The most common mechanism of trauma was traffic accident (85.4%). We found that the quality of circulatory management was unfavorable in 61% of the cases. A significant relationship was observed between the quality of circulatory management and type of trauma and staff's employment status. CONCLUSIONS: The quality of pre-hospital circulatory management provided to patients with multiple trauma was unfavorable. Therefore, establishment of in service training programs on circulatory management is recommended. PMID- 27556057 TI - Loving and Humane Care: A Missing Link in Nursing. PMID- 27556058 TI - Effectiveness of Problem-Focused Coping Strategies on the Burden on Caregivers of Hemodialysis Patients. AB - BACKGROUND: Studies have shown that family caregivers of hemodialysis patients experience high levels of burden. However, these caregivers are often neglected, and no studies are available on the effectiveness of coping strategies on the burden of care among these caregivers. OBJECTIVES: This study aimed to examine the effectiveness of problem-focused coping strategies (communication skills, anger management, and deep breathing) on the burden on caregivers of hemodialysis patients. PATIENTS AND METHODS: A randomized controlled clinical trial was conducted on 76 family caregivers of hemodialysis patients referred to Shahid Hasheminejad hemodialysis center in Tehran, Iran. The subjects were equally allocated into two groups of 38. Through a coin-tossing method, caregivers of patients who referred on even or odd days of the week were randomly assigned into the intervention group or the control group, respectively. The intervention group received four training sessions on problem-focused coping strategies, but the control group did not receive any intervention. Both groups answered the caregiver's burnout inventory at the start and six weeks after the last educational session. Descriptive statistics, chi-square, Fisher's exact test, independent-samples t-test, and Mann-Whitney U test were used to analyze the data. RESULTS: The majority of caregivers (54%) were in the age range of 35 - 55 years, female (68.4%), and married (70%). No significant difference was found between the baseline mean caregivers' burden scores of the intervention and control groups (88.56 +/- 11.74 vs. 84.97 +/- 15.13, P = 0.308). However, the mean caregivers' burden in the intervention group decreased, and the two groups were significantly different at the end of the study (58.77 +/- 6.64 vs. 87.84 +/ 11.74, P < 0.001). CONCLUSIONS: The current study showed the effectiveness of problem-focused coping strategies on reducing the burden on caregivers of hemodialysis patients. Authorities and policymakers in the healthcare system are responsible for developing strategies to integrate educational programs, such as the program implemented in the current study, into the country's healthcare system. PMID- 27556060 TI - TFEB overexpression promotes glycogen clearance of Pompe disease iPSC-derived skeletal muscle. AB - Pompe disease (PD) is a lysosomal disorder caused by acid alpha-glucosidase (GAA) deficiency. Progressive muscular weakness is the major symptom of PD, and enzyme replacement therapy can improve the clinical outcome. However, to achieve a better clinical outcome, alternative therapeutic strategies are being investigated, including gene therapy and pharmacological chaperones. We previously used lentiviral vector-mediated GAA gene transfer in PD patient specific induced pluripotent stem cells. Some therapeutic efficacy was observed, although glycogen accumulation was not normalized. Transcription factor EB is a master regulator of lysosomal biogenesis and autophagy that has recently been associated with muscular pathology, and is now a potential therapeutic target in PD model mice. Here, we differentiated skeletal muscle from PD patient-specific induced pluripotent stem cells by forced MyoD expression. Lentiviral vector mediated GAA and transcription factor EB gene transfer independently improved GAA enzyme activity and reduced glycogen content in skeletal muscle derived from PD induced pluripotent stem cells. Interestingly, GAA and transcription factor EB cooperatively improved skeletal muscle pathology, both biochemically and morphologically. Thus, our findings show that abnormal lysosomal biogenesis is associated with the muscular pathology of PD, and transcription factor EB gene transfer is effective as an add-on strategy to GAA gene transfer. PMID- 27556059 TI - PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina. AB - Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell types that endogenously express Pax6: ganglion, amacrine, horizontal, and Muller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia. PMID- 27556061 TI - Griseofulvin associated with drug reaction with eosinophilia and systemic symptoms (DRESS). PMID- 27556062 TI - Carcinoma en cuirasse caused by pleomorphic lobular carcinoma of the breast in a man. PMID- 27556063 TI - Renal transplantation-related risk factors for the development of uterine adenomatoid tumors. AB - *We analyzed the epidemiological factors for clinical manifestations of uterine adenomatoid tumors.*Renal transplantation with immunosuppression therapy is risk factor for the development of uterine adenomatoid tumors.*The length of time on dialysis is risk factor for the development of uterine adenomatoid tumors. PMID- 27556064 TI - A case of gastric hamartomatous inverted polyp resected endoscopically. AB - We report the case of a 55-year-old woman with a tumor in the greater curvature of the upper gastric body. The tumor was incidentally found on an upper gastrointestinal X-ray series performed during a routine medical examination. Whereas endoscopy revealed a gastric submucosal tumor (SMT), endoscopic ultrasonography demonstrated a heterogeneous tumor with small, cystic, hypoechoic spots originating from the second layer. The patient was clinically asymptomatic, with no contributory family history or abnormal laboratory data. The results of a physical examination, abdominal computed tomography, and plain chest radiography were all unremarkable. Although the endoscopic tumor type was determined to be SMT, the tumor was successfully resected by endoscopic submucosal dissection (ESD) and subsequently diagnosed as a gastric hamartomatous inverted polyp (GHIP). The findings of the present case highlight the importance of considering GHIP as a diagnosis and indicate the utility of en bloc resection of GHIP with ESD. PMID- 27556065 TI - Colonic transendoscopic enteral tubing: A novel way of transplanting fecal microbiota. AB - BACKGROUND AND STUDY AIMS: Placement of a tube through the anus into the cecum has not yet been established as a method of administering whole-colonic treatment. The aim of this study was to evaluate the safety, feasibility, and value of transendoscopic enteral tubing (TET) for fecal microbiota transplantation (FMT) through the colon. PATIENTS AND METHODS: A prospective observational study was performed of FMT using a new colonic TET technique. Under endoscopic guidance, a TET tube was affixed to the cecum with clips. The safety, value, and satisfaction with the FMT by TET were evaluated. RESULTS: A total of 54 patients underwent TET. The success rate of the TET procedure was 100 % (54/54). Duration of the TET procedures was 14.8 +/- 5.8 min. During the TET tube retention period, 98.1 % (53/54) of patients were satisfied with TET. The retention time for whole-colon delivery of the fecal microbiota suspension was 12.4 +/- 2.3 days. In 88.4 % (49/54) of cases, no discomfort was reported during injection through the TET tube of the microbiota suspension. No adverse events were see in patients who required tube extubation after FMT. CONCLUSIONS: Colonic TET is a novel, safe, convenient, and reliable procedure for FMT that results in a high degree of patient satisfaction. PMID- 27556066 TI - Clinical usefulness of a single-use splinting tube for poor endoscope operability in deep colonic endoscopic submucosal dissection. AB - BACKGROUND AND STUDY AIMS: Poor endoscope operability remains a significant challenge during colorectal endoscopic submucosal dissection (ESD). We retrospectively evaluated the experience and clinical usefulness of a new single use splinting tube in deep colonic ESD in the setting of poor scope operability. PATIENTS AND METHODS: Among 691 patients with colorectal tumors treated with ESD at Hiroshima University Hospital between November 2009 and July 2015, we analyzed 20 consecutive patients who underwent deep colonic ESD using a single-use splinting tube because of poor scope operability. Poor operability was defined as paradoxical movement of the endoscope, poor control with adhesions, and lesion motion with heartbeat or breathing. Technical and clinical success rates and adverse events were assessed. RESULTS: Paradoxical movement and poor control with adhesions were improved in all cases using the single-use splinting tube. The en bloc resection rate was 95 % (19/20) and histological en bloc resection rate was 100 % (20/20). There were no complications related to use of the splinting tube. CONCLUSIONS: Use of a single-use splinting tube helped to overcome poor scope operability in deep colonic ESD. PMID- 27556067 TI - Biodegradable esophageal stents in benign and malignant strictures - a single center experience. AB - BACKGROUND AND STUDY AIMS: Biodegradable (BD) esophageal stents were recently developed mainly for refractory benign strictures, but experience and available literature are limited. PATIENTS AND METHODS: This was a retrospective observational study. All patients who had BD stents inserted due to refractory benign esophageal strictures or malignant strictures, or were awaiting radical radiotherapy/chemotherapy or neo-adjuvant therapy and esophagectomy between March 2011 and July 2015 were included. RESULTS: Stent placement was successful in all patients. Ten patients with benign strictures (3 male, median age 80.5 years, IQR: 68.75 - 89.5) were followed-up for a median of 171.5 weeks (IQR: 24 - 177.25). The interval between dilatations prior to the first BD stent placement (median: 34.25 days, IQR: 23.06 - 48.29) was significantly shorter than the interval between the first BD stent placement and the first intervention required (median: 149.5 days, IQR: 94.25 - 209.5) and this difference was statistically significant (P = 0.012). Ten patients with esophageal cancer (8 male, median age: 69 years, IQR: 59.25 - 80.75) were included and they were followed up for a median of 36 weeks (IQR: 26 - 58). Only 1 completed radical radiotherapy successfully, but developed refractory post-radiotherapy stricture. No one proceeded to esophagectomy and 50 % required a self-expanding metal stent (SEMS) at a median of 134 days (IQR: 100 - 263) following stent placement. CONCLUSIONS: BD stents were successfully deployed in both benign and malignant strictures. They offered a prolonged dilatation-free interval in benign strictures, yet in the majority of patients, strictures recurred. In malignant strictures, stent patency was similar to that of benign strictures, which suggests a potential value in ensuring adequate oral intake during oncologic therapy. In our cohort, however, use of stents did not contribute to improved outcome. PMID- 27556068 TI - Endoscopic retrograde cholangiopancreatography in octogenarians: A population based study using the nationwide inpatient sample. AB - BACKGROUND AND STUDY AIMS: In the elderly population, there is a growing demand for minimally invasive procedures as the incidence of pancreaticobiliary disease increases with age. Patients with advanced age offer unique challenges for any procedure because they also tend to have a higher rate of baseline comorbidities and malignancy. The aim of the current study was to characterize the mortality and length of stay of octogenarians undergoing inpatient endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: Using the 2007 - 2010 Nationwide Inpatient Sample (NIS), we performed a retrospective analysis of health-related outcomes among 80- to 89-year-old patients undergoing inpatient ERCP. Surgical patients were excluded. RESULTS: An estimated 61,322 octogenarians underwent inpatient ERCP in the United States from 2007 to 2010. The mean age was 84.2 (SE 0.02) with 59.5 % (n = 36,460) of the patients being female. A large majority of the patients were white (79. %, n = 41,144) and 63.5 % (n = 38,940) had a comorbidity index of at least 2. The mean length of stay was 7.1 days (SE 0.08) with an in-hospital mortality of 3.1 % (n = 1,919). The primary discharge diagnosis was most often biliary stone disease (55.9 %, n = 34,263). A diagnosis of any infection was recorded in 45.0 % (n = 27,609) of patients. Infection was associated with a significantly higher risk of in-hospital mortality (OR 3.3, 95 % CI 2.6 - 4.2, P < 0.001). CONCLUSIONS: ERCP is now routinely being performed during inpatient admissions for octogenarians with diseases of the biliary tract. The mortality of octogenarians undergoing inpatient ERCP is higher than previous reports and is likely due to superimposed infection during the same admission. PMID- 27556069 TI - Development of a predictive model of Crohn's disease proximal small bowel involvement in capsule endoscopy evaluation. AB - BACKGROUND AND STUDY AIMS: One of the indications for capsule endoscopy (CE) is the detection of proximal small bowel (SB) involvement in Crohn's disease (CD) patients. Our aim was to assess clinical, laboratory and endoscopic predictors associated with proximal SB involvement in CD patients submitted to CE. PATIENTS AND METHODS: Retrospective multicenter study in which Lewis score (LS) was systematically determined in 190 CE of patients diagnosed with CD between 2003 and 2014. RESULTS: Significant inflammatory activity (LS > 135) was present in 23 % of the patients in the first tertile and in 31 % of the patients in the second tertile. Albumin, haemoglobin, and total proteins were significantly lower in patients with a LS > 790 compared to patients with a LS < 135, while white blood cell counts and C-reactive protein were significantly higher. In the univariable analysis, a higher risk for proximal SB involvement at CE was associated with ileal involvement at ileocolonoscopy (OR 2.858, P = 0.006), higher platelets levels (OR 1.005, P = 0.004) and significant weight loss (OR 2.450, P = 0.006). In logistic regression, ileal involvement at ileocolonoscopy (OR 6.817, P = 0.003), stricturing behavior (OR 8.653, P = 0.011) and significant weight loss (OR 3.629, P = 0.028) were independently associated with proximal SB involvement at CE. Considering the ROC curve of this model, a cut-off > 0.249 predicts proximal SB involvement with 90 % sensitivity and 40 % specificity (AUROC 0.732). CONCLUSIONS: One-third of patients had proximal SB involvement. Predictive factors were significant weight loss, stricturing behaviour, and ileal involvement at ileocolonoscopy. These data help to select CD patients that benefit the most from performing a CE. PMID- 27556070 TI - Endoscopic ultrasound-guided forceps biopsy from upper gastrointestinal subepithelial lesions using a forward-viewing echoendoscope. AB - BACKGROUND AND STUDY AIMS: Endoscopic tissue acquisition techniques using needle knife and biopsy forceps allow abundant tissue acquisition from upper gastrointestinal subepithelial lesions; however, these techniques cannot capture real-time intratumor information. The aim of this study was to evaluate the feasibility of endoscopic ultrasound-guided forceps biopsy (EUS-FB) from upper gastrointestinal subepithelial lesions using a forward-viewing echoendoscope. PATIENTS AND METHODS: This study was a prospective case series. After mucosal cuts, several specimens were taken using a hot biopsy forceps under real-time EUS visualization. The incision was closed using hemoclips. Diagnostic yield, rate of diagnosable samples obtained under EUS visualization, procedure time, and adverse events were assessed. RESULTS: Ten patients (median lesion size 16 mm, range 15 - 44 mm) underwent EUS-FB. The overall rate of histological diagnosis by EUS-FB was 100 % (10/10). The rate of diagnosable samples among all cases was 97.6 % (41/42). The median procedure times for EUS-FB and complete closure were 28.5 and 4.5 minutes, respectively. No adverse events occurred. CONCLUSIONS: This newly developed EUS-FB is feasible and allowed forceps biopsy from upper gastrointestinal subepithelial lesions. STUDY REGISTRATION: UMIN000015364. PMID- 27556071 TI - Accuracy of polyp localization at colonoscopy. AB - BACKGROUND AND STUDY AIMS: Accurate documentation of lesion localization at the time of colonoscopic polypectomy is important for future surveillance, management of complications such as delayed bleeding, and for guiding surgical resection. We aimed to assess the accuracy of endoscopic localization of polyps during colonoscopy and examine variables that may influence this accuracy. PATIENTS AND METHODS: We conducted a prospective observational study in consecutive patients presenting for elective, outpatient colonoscopy. All procedures were performed by Australian certified colonoscopists. The endoscopic location of each polyp was reported by the colonoscopist at the time of resection and prospectively recorded. Magnetic endoscope imaging was used to determine polyp location, and colonoscopists were blinded to this image. Three experienced colonoscopists, blinded to the endoscopist's assessment of polyp location, independently scored the magnetic endoscope images to obtain a reference standard for polyp location (Cronbach alpha 0.98). The accuracy of colonoscopist polyp localization using this reference standard was assessed, and colonoscopist, procedural and patient variables affecting accuracy were evaluated. RESULTS: A total of 155 patients were enrolled and 282 polyps were resected in 95 patients by 14 colonoscopists. The overall accuracy of polyp localization was 85 % (95 % confidence interval, CI; 60 - 96 %). Accuracy varied significantly (P < 0.001) by colonic segment: caecum 100 %, ascending 77 % (CI;65 - 90), transverse 84 % (CI;75 - 92), descending 56 % (CI;32 - 81), sigmoid 88 % (CI;79 - 97), rectum 96 % (CI;90 - 101). There were significant differences in accuracy between colonoscopists (P < 0.001), and colonoscopist experience was a significant independent predictor of accuracy (OR 3.5, P = 0.028) after adjustment for patient and procedural variables. CONCLUSIONS: Accuracy of localization of polyps is imprecise and affected by position within the colon and colonoscopist, including their level of experience. Magnetic endoscope imaging may improve the localization of lesions during colonoscopy. PMID- 27556072 TI - Endoscopic internal drainage as first-line treatment for fistula following gastrointestinal surgery: a case series. AB - BACKGROUND AND STUDY AIMS: Leaks following gastrointestinal surgery are a dreadful complication burdened by high morbidity and not irrelevant mortality. Endoscopic internal drainage (EID) has showed optimal results in the treatment of leaks following bariatric surgery. We report our experience with EID as first line treatment for fistulas following surgery along all gastrointestinal tract. PMID- 27556073 TI - Digestive leaks: An approach tailored to both indication and anatomy. PMID- 27556074 TI - A comparative study of grasping-type scissors forceps and insulated-tip knife for endoscopic submucosal dissection of early gastric cancer: a randomized controlled trial. AB - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is technically difficult for beginners. Few comparative studies of technical feasibility, efficacy, and safety using various devices have been reported. This study evaluated the feasibility, efficacy, and safety of ESD for EGC < 2 cm using grasping-type scissors forceps (GSF) or insulated-tip knife (IT2) for three resident endoscopists. PATIENTS AND METHODS: This was a randomized phase II study in a cancer referral center. A total of 108 patients with 120 EGCs were enrolled with the following characteristics: differentiated type mucosal EGC, without ulcers or scars, < 2 cm (86 men, 22 women; median age 72 years). All lesions were stratified according to operator and tumor location (antrum or corpus), assigned randomly to two groups (GSF or IT2), and resected by ESD. Self-completion rate, complete resection rate, procedure time, and adverse events were evaluated as main outcome measures. RESULTS: There was no difference in self-completion rate between the IT2 group (77 %, 47/61, P = 0.187) and the GSF group (66 %, 37/56). Also, there were no differences in en bloc resection rate (98 %, 60/61 vs. 93 %, 52/56, P = 0.195) and adverse events (3.3 %, 2/61 vs. 7.1 %, 4/56, P = 0.424). Median (min [range]) procedure time in the IT2 group (47 [33 - 67], P = 0.003) was shorter than that in the GSF group (66 [40 - 100]). Limitations of this study were the small sample size and single center design. CONCLUSIONS: ESD with GSF did not show a statistically significant advantage in improvement of self-completion rate over IT2. ( STUDY REGISTRATION: UMIN 000005048). PMID- 27556075 TI - Filling and shielding for postoperative gastric perforations of endoscopic submucosal dissection using polyglycolic acid sheets and fibrin glue. AB - BACKGROUND AND STUDY AIMS: Many medical institutions in Japan perform endoscopic mucosal dissection (ESD) to treat early gastric cancer. Perforations can occur during ESD, and clipping has been reported as useful for treating small pinhole perforations. However, it is often difficult to close postoperative perforations because they usually have large diameters, and the muscle layer around the perforated region is often fragile, so additional open surgery is the only currently used method to treat large perforations and delayed perforations. Another method for large perforation is needed to treat perforations endoscopically. Ono et al. reported a case in which a postoperative perforation was closed using a polyglycolic acid (PGA) sheet and fibrin glue. In addition, it has been used by the authors' group to repair duodenal injuries that occur during ESD. We report 3 cases in which PGA sheets and fibrin glue were successfully used to repair postoperative gastric perforations endoscopically. This method is simple, safe, and effective, and is a new way to treat large perforations and delayed perforations that occur following ESD. PMID- 27556076 TI - Therapeutic or spontaneous Helicobacter pylori eradication can obscure magnifying narrow-band imaging of gastric tumors. AB - BACKGROUND AND STUDY AIMS: We previously reported that narrow-band imaging with magnifying endoscopy (NBI-ME) revealed a unique "gastritis-like" appearance in approximately 40 % of early gastric cancers after Helicobacter pylori eradication. Because rates of gastric cancer are increasing in patients with non persistent infection of H. pylori, we aimed to clarify contribution factors to obscure tumors after therapeutic or spontaneous eradication. PATIENTS AND METHODS: NBI-ME findings were examined retrospectively in 194 differentiated-type adenocarcinomas from H. pylori-negative patients with prior eradication therapy (83 patients) or without prior eradication therapy (72 patients). A gastritis like appearance under NBI-ME was defined as an orderly microsurface structure and/or loss of clear demarcation with resemblance to the adjacent, non-cancerous mucosa. The correlation of this phenomenon with the degree of atrophic gastritis, determined both histologically in the adjacent mucosa and endoscopically, was evaluated. RESULTS: The tumor-obscuring gastritis-like appearance was observed in 42 % and 23 % of the patients in the H. pylori eradication and non-eradication groups, respectively. The development of this appearance was affected by the histological grade of atrophy (P = 0.003) and intestinal metaplasia (P < 0.001) on univariate analysis. Multivariate analysis revealed an odds ratio of 0.25 (95 % confidence interval 0.10 - 0.61, P = 0.002) for an endoscopically severe extent of atrophy, independently of eradication therapy. CONCLUSIONS: An endoscopically mild or moderate extent of atrophy is associated with a gastritis-like appearance under NBI-ME in currently H. pylori-negative gastric cancers. Surveillance endoscopy should be performed carefully after successful eradication or spontaneous elimination of H. pylori, particularly in patients with non-severe atrophic background mucosa. PMID- 27556077 TI - Endoscopic extraction of adjustable gastric bands after intragastric migration as a complication of bariatric surgery: technique and advice. AB - BACKGROUND: Surgery has been the method most widely used to manage the extraction of gastric bands with inclusion as a late complication of bariatric surgery; however, surgical extraction entails morbidity and limits future surgical procedures. The development of endoscopic techniques has provided an important means of improving the treatment of this complication, enabling minimally invasive and safe procedures that have a high success rate. METHODS: A retrospective analysis was conducted of patients who had laparoscopic gastric banding complicated by intragastric migration and were treated endoscopically. A technique already described for managing this complication was employed. An MTW Endoskopie Dormia basket for mechanical lithotripsy or a standard 0.0035-in guidewire was placed around the band, and an MTW Endoskopie emergency lithotripter was used to section it, after which the band was extracted with a standard polypectomy snare. Also analyzed were the initial symptoms of patients with this complication, the mean time from surgery to development of the event, the success rate of endoscopic treatment, and complications, Results: A total of 127 patients had undergone gastric banding surgery in our Bariatric Surgery Center; of these, 12 patients (9.4 %) developed a complication such as intragastric migration of the band. Weight gain and pain were the main symptoms in 11 patients (92 %), and the mean time to the development of symptoms was 51.3 months. A single endoscopic treatment was successful in 7 of 9 patients (78 %). Only 1 complication, involving ventilation during anesthesia, occurred; no other adverse events were recorded. CONCLUSIONS: The endoscopic extraction of bands with inclusion is feasible and can be performed easily and successfully. The procedure is available in all hospitals and has a low incidence of related complications, so that unnecessary surgical procedures can be avoided. PMID- 27556078 TI - Endoscopic versus surgical approach in the treatment of Zenker's diverticulum: systematic review and meta-analysis. AB - BACKGROUND: Zenker's diverticulum is a rare disease in the general population. Its treatment can be carried out by either an endoscopic or surgical approach. The objective of this study was to systematically identify all reports that compare both treatment modalities and to assess the outcomes in terms of length of procedure, length of hospitalization, time until diet introduction, complication rates, and recurrence rates. METHODS: A search of Medline and Embase selected all studies that compared different methods of surgical and endoscopic treatment for Zenker's diverticulum published in the English, Portuguese, and Spanish languages between 1975 and 2014. The meta-analysis was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta analyses (PRISMA) statement. Data were extracted and analyzed for five different outcomes. RESULTS: Eleven studies met the inclusion criteria, describing outcomes of endoscopic versus surgical treatment for 596 patients with Zenker's diverticulum. A meta-analysis of the studies suggested a statistically significant reduction in operating time and length of hospitalization, favoring endoscopic treatment (standardized mean difference (SMD) - 78.06, 95 %CI - 90.63, - 65.48 and SMD - 3.72, 95 %CI - 4.49, - 2.95, respectively), just as with the reduction in the fasting period (SMD - 4.30, 95 %CI - 5.18, - 3.42) and risk of complications (SMD - 0.09, 95 %CI 0.03, 0.43) for patients who had undergone the endoscopic approach in comparison with the surgical group. Also, a statistically significant reduction in the risk of symptom recurrence was seen when the treatment of Zenker's diverticulum was carried out by a surgical approach compared with endoscopic treatment (SMD 0.08, 95 %CI 0.03, 0.13). CONCLUSION: Compared with a surgical approach, endoscopic treatment appeared to result in a shorter length of procedure and hospitalization, earlier diet introduction, and lower rates of complications, but in higher rates of symptom recurrence. PMID- 27556079 TI - Flat-type primary malignant melanoma of the esophagus. PMID- 27556080 TI - Magnifying endoscopy with narrow-band imaging is more accurate for determination of horizontal extent of early gastric cancers than chromoendoscopy. AB - BACKGROUND AND STUDY AIMS: Although magnifying endoscopy with narrow-band imaging (ME-NBI) is reported to be useful for delineating the horizontal extent of early gastric cancers (EGCs), there are few reports which have objectively demonstrated the superiority of ME-NBI over chromoendoscopy with indigo carmine for this purpose. We conducted an exploratory comparison of the diagnostic accuracy of both modalities for the delineation of EGCs using prospectively collected data, and clarified the clinicopathological features related to inaccurate evaluation of the horizontal extent of EGCs. PATIENTS AND METHODS: EGCs were assigned to the oral narrow-band imaging (O-NBI) group or the oral chromoendoscopy (O-CE) group before endoscopic submucosal dissection (ESD). The oral border was observed according to assignment, and the anal border with the other modality. The horizontal extent of the tumor was evaluated by each modality and a marking dot was placed on the visible delineation line. After ESD, the marking dots were identified pathologically and defined as "accurate evaluation" if they were located within 1 mm of the pathological tumor border. We compared the rate of accurate evaluation of ME-NBI and chromoendoscopy, and analyzed the clinicopathological features related to inaccurate evaluation. RESULTS: A total of 113 marking dots evaluated by ME-NBI and 116 evaluated by chromoendoscopy were analyzed. The rate of accurate evaluation by ME-NBI was significantly higher than that by chromoendoscopy (89.4 % vs 75.9 %, P = 0.0071). The EGCs with flat borders and large EGCs were significantly related to inaccurate evaluation using ME-NBI. There were no significant factors related to inaccurate evaluation with chromoendoscopy. CONCLUSIONS: The accurate evaluation rate of the horizontal extent of EGCs by ME-NBI is significantly higher than that by chromoendoscopy. STUDY REGISTRATION: UMIN000007641. PMID- 27556081 TI - Efficacy and safety of endoscopic mucosal resection of non-ampullary duodenal polyps: a systematic review. AB - BACKGROUND AND AIMS: Data on the safety and efficacy of endoscopic resection of non-ampullary duodenal polyps are limited. This study evaluated the safety and efficacy of endoscopic mucosal resection (EMR) of sporadic non-ampullary duodenal polyps. METHODS: Relevant studies for the meta-analysis were identified through search of PUBMED and EMBASE databases. Studies employing EMR for the management of sporadic duodenal polyps in the non-ampullary region were included. The primary outcome was the surgical intervention rates due to non-curative endoscopic resection (incomplete removal/recurrence necessitating surgery) and/or management of procedural adverse events. RESULTS: A total of 440 patients (485 duodenal polyps) from 14 studies were included. The mean size of the polyps was 13 mm to 35 mm. Surgical intervention due to non-curative EMR and adverse events was required in 2 % (95 % confidence interval [CI] 0 - 4 %). EMR was successfully accomplished in 93 % (95 %CI 89 - 97 %). The overall bleeding rate after EMR was 16 % (95 %CI 10 - 23 %), and the pooled delayed bleeding rate was 5 % (95 %CI 2 - 7 %). The overall incidence of perforation was 1 % (95 %CI 1 - 3 %). Over a median follow-up period of 6 - 72 months, the recurrence rate after EMR was 15 % (95 %CI 7 - 23 %). Six studies (pooled recurrence 20 %, 95 %CI 14 - 27 %) reported on the outcomes of managing recurrent polyps, for which endoscopic removal was successful in 62 % (95 %CI 37 - 87 %). There was no procedure related mortality. CONCLUSION: EMR appears to be a safe and effective therapeutic option for management of sporadic non-ampullary duodenal polyps. Long-term endoscopic surveillance is required to manage and treat recurrent disease. PMID- 27556082 TI - Gastric ulcers: malignancy yield and risk stratification for follow-up endoscopy. AB - BACKGROUND AND STUDY AIM: Malignant change can occur in gastric ulcer but guideline recommendations for follow-endoscopy (FU-OGD) are conflicting. This study aims to determine rate of malignancy and need for follow-up for gastric ulcers. PATIENTS AND METHODS: Patients with a first diagnosis of gastric ulcer between January 2012 and September 2013 were studied by analyzing endoscopic assessments, dysplasia, and malignancy yield and the influence of risk factors on the likelihood of benign disease. RESULTS: In a cohort of 432 patients with gastric ulcer (53 % male, mean age 65 years) dysplasia or neoplasia were found in 27 (19 adenocarcinomas, 2 cases of dysplasia, 5 lymphomas, 1 melanoma; malignancy yield 6 %). Twenty-five (93 %) cases were diagnosed on first biopsy. The cancer yield of FU-OGD after initially benign biopsy was 0.9 %. Binary logistic regression analysis revealed that endoscopically benign appearance (odds ratio 0.004 95 % CI 0 - 0.576; P = 0.029), benign histology on first biopsy (odds ratio 0 95 % CI 0 - 0.39; P = 0.011) and lower number of ulcers (odds ratio 0.22 (95 % CI 0.05 - 0.99); P = 0.049) were independent predictors of benign disease. All dysplastic and neoplastic cases would have been identified by a combination of initial biopsies plus repeat endoscopy with further biopsies for endoscopically suspicious appearances. CONCLUSIONS: In this large cohort 6 % of gastric ulcers were found to be malignant, highlighting the need for all gastric ulcers to be biopsied. The cancer yield of FU-OGD after benign biopsies was low. We have demonstrated that the combination of benign index histology and no endoscopic suspicion of malignancy can predict benign disease. We recommend that all gastric ulcers to be biopsied. Risk stratification could potentially reduce need for FU OGD. PMID- 27556083 TI - Prospective evaluation of the clinical utility of endoscopic submucosal dissection (ESD) in patients with Barrett's esophagus: a Western center experience. AB - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) carries significant advantages over endoscopic mucosal resection. As such, ESD is an established therapy for esophageal squamous cell carcinoma but there are only limited data on ESD as therapy for Barrett's esophagus (BE). Thus, we prospectively evaluated the outcomes of ESD in patients with BE with high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) performed in a Western center. PATIENTS AND METHODS: This is a prospective cohort study. Indications for ESD included: (1) early EAC defined as lesions with intramucosal cancer or superficial submucosal invasion; (2) early EAC with positive lateral margin after EMR; and (3) nodularity with HGD that could not be removed en-bloc with EMR Results: From October 2013 to July 2015, 36 consecutive patients (median age 69, 32 males) underwent ESD at our center. Median procedure time was 88 minutes, with median maximal diameter of resected specimens of 49 mm. En-bloc, R0, and curative resection rates were 100 %, 81 %, and 69 %, respectively. Intramucosal EAC was found in 13 patients (36 %), and submucosal invasion in 13 patients (36 %). In 59 % of the cases, there was discrepancy in the pre- and post-ESD histopathologic diagnosis. Adverse events occurred in 8 patients (22 %), including one episode of bleeding treated with endoscopy and seven esophageal strictures, which were successfully managed with dilations. CONCLUSIONS: ESD for BE with HGD/early EAC is feasible and safe with resulting very high en-bloc and R0 resection rates. ESD provided for more accurate pathologic evaluation and significant discrepancy between the pre- and post-ESD histopathological diagnosis was noted. PMID- 27556084 TI - Barrett's esophagus: The advocacy for ESD. PMID- 27556085 TI - Antireflux versus conventional self-expanding metallic Stents (SEMS) for distal esophageal cancer: results of a multicenter randomized trial. AB - INTRODUCTION: Self-expanding metal stents (SEMS) are commonly used in the palliation of dysphagia in patients with inoperable esophageal carcinoma. However, they predispose to gastroesophageal reflux when deployed across the gastroesophageal junction. The aims of this study were to: 1) assess the influence of the antireflux valve on trans-prosthetic reflux (primary outcome); and 2) compare the results of SEMS with and without antireflux valve in terms of reflux symptoms, quality of life (QOL), improvement of dysphagia and adverse events (secondary outcomes). PATIENTS AND METHODS: Thirty-eight patients were enrolled in nine centers. Carcinomas were locally advanced (47 %) or metastatic. After randomization, patients received either a covered SEMS with antireflux valve (n = 20) or a similar type of SEMS with no antireflux device but assigned to standard proton pump inhibitor therapy and postural advice (n = 18). Trans prosthetic reflux was assessed at day 2 using a radiological score based on barium esophagography performed after Trendelenburg maneuver and graded from 0 (no reflux) to 12 (maximum). Monthly telephone interviews were conducted for Organisation Mondiale de la Sante (OMS) scoring from 0 (excellent) to 5 (poor), QOL assessment (based on the Reflux-Qual Simplifie scoring system) from 0 (poor) to 100 (excellent), dysphagia scoring from 0 (no dysphagia) to 5 (complete dysphagia) and regurgitation scoring from 0 (no regurgitation) to 16 (maximum). RESULTS: No difference was noted in terms of age, sex, size of lesion, prosthesis length or need for dilation prior to SEMS placement. No difficulty in placing SEMS nor complications were noted. Radiological scores of reflux were found to be significantly lower in patients with an antireflux stent compared to the conventional stent and associated measures. The regurgitation scores were significantly decreased in patients with antireflux stents during the first 2 months after stent placement and thereafter, they were similar in the two groups. QOL and dysphagia were improved in both groups. Survival rates were comparable in the two groups. CONCLUSIONS: No difference was observed between the two types of SEMS regarding the palliation of dysphagia and improvement of QOL. However, SEMS with an antireflux valve were more effective in preventing trans-prosthetic gastroesophageal reflux but at the cost of an increased likehood of minor adverse events (migrations and/or obstruction of the SEMS). PMID- 27556086 TI - Use of percutaneous endoscopic colostomy (PEC) to treat sigmoid volvulus: a systematic review. AB - BACKGROUND AND AIM: Percutaneous endoscopic colostomy provides an alternative management option for patients with recurrent sigmoid volvulus who are considered too high risk to undergo surgery. We reviewed the literature to assess whether the National Institute for Health and Clinical Excellence guidelines published in 2006 supporting the use of percutaneous endoscopic colostomy are still valid. METHODS: A systematic literature search was conducted using PubMed, Web of Science, and Embase. The exploded search terms "Percutaneous Endoscopic Colostomy" and "Sigmoid Volvulus" were used. Librarian support was used to ensure the maximum number of relevant articles were returned. Identified abstracts were then analyzed and included if they met the inclusion criteria. RESULTS: Five observational studies and 5 case reports were identified that met the inclusion criteria. They provided data on 56 patients with recurrent sigmoid volvulus treated with percutaneous endoscopic colostomy placement. Sixteen of the 56 patients were treated with a single percutaneous endoscopic colostomy (PEC) tube while 38 patients were treated with 2 PEC tubes. For 2 patients the details of the procedure were unknown. Five patients developed major complications following the procedure: 1 patient developed peritonitis after 4 days, due to fecal contamination secondary to tube migration and 2 patients with cognitive impairment pulled their PEC tubes out. Two other patients died following PEC insertion. Nine patients developed minor complications following the procedure. The most commonly reported minor complication was infection at the PEC site. Four of 56 patients developed a recurrent sigmoid volvulus with a PEC tube in situ. CONCLUSION: Although in these case series there is a 21 % risk of morbidity and 5 % risk of mortality from the use of a PEC, this is favorable compared to the mortality risk of 6.6 % to 44 % reported with operative intervention. This review of contemporary literature therefore supports the use of PEC in frail and elderly patients. PMID- 27556087 TI - Should we recommend PEC and when? PMID- 27556088 TI - Primary micropapillary carcinoma of the colon with submucosal invasion: A case report. AB - BACKGROUND AND STUDY AIMS: We present a case of invasive micropapillary carcinoma (IMPC) of the colon treated by endoscopic resection following magnifying endoscopy. A 47-year-old woman visited our hospital for follow-up of a positive fecal occult blood test. Colonoscopy revealed a semi-pedunculated reddish polyp, the surface of which showed gentle irregularity, and mild tension in the sigmoid colon. Magnifying colonoscopy with narrow band imaging revealed an irregular surface pattern with heterogeneity in vascular diameter and distribution. Magnifying endoscopic findings using crystal violet staining showed an irregular pit pattern with an expansion of stromal areas. Endoscopic resection of the sigmoid colon tumor was performed, and the histology of the resected specimen primarily revealed a micropapillary component with a small moderately differentiated adenocarcinoma component that massively invaded into the submucosal layer, accompanied by lymphatic invasion, although the tumor was very small (7 mm in diameter, smaller than any in previous reports). Laparoscopy assisted sigmoidectomy and regional lymph node resection were performed; neither cancer nor lymph node metastases were present. This is the first report of a case with early-stage colonic IMPC observed with magnifying colonoscopy. PMID- 27556089 TI - Adjunctive radiofrequency ablation for the endoscopic treatment of ampullary lesions with intraductal extension (with video). AB - BACKGROUND AND STUDY AIMS: Catheter-based radiofrequency ablation (RFA) delivered during endoscopic retrograde cholangiopancreatography (ERCP) may represent a viable treatment option for intraductal extension of ampullary neoplasms, however, clinical experience with this modality is limited. After ampullary resection, 4 patients with intraductal extension underwent adjunctive RFA of the distal bile duct. All patients received a temporary pancreatic stent to reduce the risk of pancreatitis, as well as a plastic biliary stent to prevent biliary obstruction. Three patients were treated for adenoma and 1 for adenoma with a focus of adenocarcinoma. During a short follow-up period, 3 patients experienced complete eradication of the target lesion, whereas the patient with a focus of adenocarcinoma had progression to overt invasive cancer. There were no immediate adverse events. One patient developed a post-RFA bile duct stricture, which has required additional endoscopic therapy. Catheter-based RFA of ampullary lesions that extend up the bile duct is technically feasible. Additional research is necessary to understand the risks and long-term benefits of this technique. PMID- 27556090 TI - Endoscopic surveillance of head and neck cancer in patients with esophageal squamous cell carcinoma. AB - BACKGROUND AND STUDY AIMS: Multiple squamous cell carcinomas (SCCs) frequently arise in the upper aerodigestive tract, referred to as the field cancerization phenomenon. The aim of this study was to elucidate the detailed clinical features of second primary head and neck (H&N) SCCs arising in patients with esophageal SCC. PATIENTS AND METHODS: A total of 818 patients underwent endoscopic resection for superficial esophageal cancer between January 2006 and December 2013. Of these, 439 patients met our inclusion criteria, and we retrospectively investigated the incidence, primary sites, and stages of second primary H&N SCCs in these patients. RESULTS: A total of 53 metachronous H&N SCCs developed in 40 patients after a median follow-up period of 46 months (range 9 - 109). The cumulative incidence rates of metachronous H&N SCCs at 3, 5, and 7 years were 5.3 %, 9.7 %, and 17.2 %, respectively. These lesions were frequently located at pyriform sinus or in the posterior wall of the pharynx (70 %, 37/53 lesions). Most of the lesions were detected at an early stage, though 4 lesions were associated with lymph node metastasis when their primary sites were detected (1 postcricoid area, 2 posterior wall of hypopharynx, and 1 lateral wall of oropharynx). CONCLUSIONS: Patients with esophageal SCC should undergo careful inspection of the pyriform sinus and posterior wall of the pharynx for detection of H&N SCCs. Methods to open the hypopharyngeal space, such as the Valsalva maneuver, should be included in the surveillance program. PMID- 27556091 TI - Rare condition of needle tract seeding after EUS-guided FNA for intraductal papillary mucinous carcinoma. AB - BACKGROUND AND STUDY AIMS: We report on a 75-year-old man who was admitted due to pancreatic cystic lesion accompanied by a solid mass with liver metastasis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed on the solid mass, and pathological findings revealed the lesion to be an adenocarcinoma diagnosed as intraductal papillary mucinous carcinoma (IPMC). Approximately 3 months after, a cystic subepithelial lesion appeared in the posterior gastric wall where the EUS-FNA had been performed. We performed EUS-FNA again, which revealed that the cystic mass was IPMC with pathology similar to the original lesion. This is a rare case demonstrating needle tract seeding of EUS FNA for IPMC. PMID- 27556092 TI - PEG closure in the second attempt. AB - BACKGROUND AND STUDY AIMS: This case report demonstrates successful endoscopic treatment of a persistent gastrocutaneous fistula after removal of a percutaneous endoscopic gastrostomy (PEG) in a 21-year-old patient with mucoviscidosis after lung transplantation. Because the initial OTSC clip (gastric) did not close the fistula sufficiently, we had to remove it and replace it with a larger OTSC clip (colon) in a second intervention. That clip finally sufficiently closed the fistula. PMID- 27556093 TI - Timing of single balloon enteroscopy: significant or not? AB - BACKGROUND: The development of balloon assisted enteroscopy (BAE) has revolutionized diagnostic and therapeutic modalities for small-bowel disorders. Although the role of emergent esophagogastroduodenoscopy and colonoscopy for upper and lower gastrointestinal bleeding is well defined, there is scarce data with regard to emergent BAE for gastrointestinal bleeding. STUDY: We performed a retrospective cohort study including 110 hospitalized patients with obscure gastrointestinal bleeding who underwent single balloon enteroscopy (SBE) between January 2010 and August 2013. Patients were divided into two groups based on procedures performed emergently (within 24 hours) versus non-emergently (greater than 24 hours). Data on patient demographics, hemodynamic characteristics, type of obscure bleed, lesions identified, location of lesions, endoscopic intervention performed, need for further surgical or radiological intervention, diagnostic and therapeutic yield, and adverse events were compared between groups. Independent samples t test and Fisher's exact test were used to assess the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and 95 % confidence intervals (CI), and for binary as odds ratio and 95 %CI. RESULTS: Although patients in the group where enteroscopy was performed within 24 hours had a significantly higher incidence of radiological intervention (10.0 % vs. 0.0 %, P = 0.019), the diagnostic and therapeutic yields between the two groups were not significantly different. Additionally, there were no statistically significant differences between the groups for overt and occult bleeding, transfusion requirements, type and location of lesions, endoscopic intervention performed, or adverse events. Hospital stay was shorter in the patients who had SBE within 24 hours of admission (6.2 vs. 11.3 days, P < 0.001). CONCLUSIONS: Although the diagnostic and therapeutic yields of SBE were not significantly different between patients having the procedure within 24 hours and those having it later, the early SBE group required more interventional radiology procedures. While endoscopists may not necessarily have to perform emergent assessment within 24 hours in patients with obscure gastrointestinal bleeding (OGIB) for greater diagnostic or therapeutic yield, early intervention may allow for earlier stabilization and thus shorter hospital stays. Prospective studies further evaluating these findings are indicated. PMID- 27556094 TI - Endoscopic evaluation of celiac disease severity and its correlation with histopathological aspects of the duodenal mucosa. AB - BACKGROUND AND STUDY AIMS: Celiac disease (CD) is a chronic systemic autoimmune disorder affecting genetically predisposed individuals, triggered and maintained by the ingestion of gluten. Triggered and maintained by the ingestion of gluten, celiac disease is a chronic systemic autoimmune disorder affecting genetically predisposed individuals. Persistent related inflammation of the duodenal mucosa causes atrophy architecture detectable on esophagogastroduodenoscopy (EGD) and histopathology. We investigated the association between endoscopic features and histopathological findings (Marsh) for duodenal mucosa in celiac disease patients and propose an endoscopic classification of severity. PATIENTS AND METHODS: Between January 2000 and March 2010, an electronic database containing 34,540 EDGs of patients aged > 14 years was searched for cases of CD. Out of 109 cases, 85 met the inclusion criteria: conventional EGD combined with chromoendoscopy, zoom and biopsy. EGD types 0, I and II corresponds to Marsh grades 0, 1 and 2, respectively, while EGD type III corresponds to Marsh grade 3 and 4. RESULTS: Five patients (5.8 %) were EGD I but not Marsh grade 1; 25 patients (29.4 %) were EGD II, 4 of whom (16 %) were classified as Marsh grade 2; and 55 patients (64.7 %) were EGD III, 51 (92.7 %) of whom were classified as Marsh grades 3 and 4. The Spearman correlation coefficient (r = 0.33) revealed a significant association between the methods (P = 0.002). CONCLUSIONS: Changes in the duodenal mucosa detected on EGD were significantly and positively associated with histopathologic findings. The use of chromoendoscopy in addition to conventional EGD enhances changes in the duodenal mucosa and permits diagnosis of CD, even in routine examinations. The proposed endoscopic classification is practical and easily reproducible and provides valuable information regarding disease extension. PMID- 27556095 TI - Optical diagnosis of malignant colorectal polyps: is it feasible? AB - BACKGROUND AND STUDY AIMS: As colorectal cancer screening programs are being implemented worldwide, an increasing number of early (T1) cancers are being diagnosed. These cancers should be recognized during colonoscopy because they require a specific therapeutic approach. Several studies have shown that Asian experts can reliably recognize T1 cancers during colonoscopy. In daily practice, however, accurate endoscopic diagnosis of T1 cancers still seems challenging. We evaluated the performance of optical diagnosis of T1 cancers by European colonoscopy experts, general gastroenterologists and gastrointestinal fellows. PATIENTS AND METHODS: We collected endoscopic images of 43 colonic lesions: 19 T1 cancers (excluding intramucosal carcinoma) and 24 benign polyps ranging from 7 mm to 30 mm in size. Seven colonoscopy experts, 7 general gastroenterologists, and 14 gastrointestinal fellows assessed these images. We calculated sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) and their 95 % confidence intervals for optical diagnosis of T1 cancers. RESULTS: Overall sensitivity for correct diagnosis of T1 cancers was 60 % (95 % CI;45 - 72). Sensitivity was highest for experts (67 %: 95 %CI; 48 - 81), when compared to general gastroenterologists (53 %: 95 %CI; 37 - 69) and gastrointestinal fellows (59 %: 95 %CI;45 - 72). The overall NPV was 75 % (95 %CI;60 - 86); NPV was lowest for general gastroenterologists 72 % (95 %CI;57 - 83) vs 78 % (95 %CI;63 - 89) for experts and 75 % (95 %CI;60 - 85) for gastrointestinal fellows. CONCLUSIONS: In this image-based study, both sensitivity for the optical diagnosis of a T1 cancer and NPV for excluding a T1 cancer were insufficient. Experts performed best with a sensitivity of 67 % and a NPV of 78 %, while the performance of fellows in the last year of training was comparable to that of experts. Our study indicates that training for endoscopic diagnosis for T1 cancers is urgently needed to ensure optimal clinical practice for treatment of these lesions. PMID- 27556096 TI - Novel technique of endoscopic full-thickness resection for superficial nonampullary duodenal neoplasms to avoid intraperitoneal tumor dissemination. AB - BACKGROUND AND STUDY AIMS: Recently, laparoscopic and/or endoscopic full thickness resection (FTR) has been reported to be a useful technique for the treatment of superficial duodenal neoplasms (SDNs). In the current study, we evaluated clinical outcomes in 5 consecutive patients who underwent resection of nonampullary SDNs using laparoscopy-assisted endoscopic full-thickness resection with ligation Device (LAEFTR-L), which is an alternative FTR method developed to avoid peritoneal dissemination. Using a snare technique with a ligation band, the duodenal lesions were easily resected. The provisional and additional sutures for the resected site prevented delayed perforation and bleeding and they also protected the abdominal cavity from direct exposure to malignant cells. Complete resection could be achieved and FTR was histologically confirmed in all cases. The mean operation time was 173 minutes (range 138 - 217 minutes). Mean diameter of the resected specimen was 24 mm (range 18 - 32 mm). No adverse events (AEs) were observed. LAEFTR-L, which can achieve complete resection of nonampullary SDNs without severe AEs and peritoneal dissemination, could be a useful technique for the treatment of such lesions. PMID- 27556098 TI - Management of long post-radiation esophageal strictures by means of endoscopic submucosal dissection. PMID- 27556097 TI - Factors associated with incomplete gastric endoscopic submucosal dissection due to misdiagnosis. AB - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is widely accepted for treating early gastric cancer (EGC); however, there can be cases of incomplete resection due to not only technical problems, but also misdiagnosis. Our aim was to identify factors associated with incomplete gastric ESD due to misdiagnosis. PATIENTS AND METHODS: A total of 2,268 patients with solitary EGCs at initial onset underwent ESD with curative intent at our hospital from 1999 to 2008. We retrospectively assessed the clinicopathological factors by comparing the two groups of incomplete ESD cases due to misdiagnosis (cases with a positive lateral margins [LM] [Group A] or those with a positive vertical margins [VM] [Group B]) with complete ESD cases using multivariable analysis. RESULTS: Complete ESD was achieved in 2,097 patients. The 171 patients with incomplete ESDs were divided into 109 with a positive LM and 80 with a positive VM (overlapped). Except 49 cases with a positive LM due to technical problems, a positive LM due to misdiagnosis was identified in 60 cases (Group A). Excluding 32 cases with a positive VM due to technical problems, a positive VM due to misdiagnosis was found in 48 cases (Group B). Significant independent factors (odds ratios [OR]; 95 % confidence intervals [CI]) for each group were as follows: Group A: size > 20 mm (5.4; 3.0 - 9.9), undifferentiated-type (4.1; 1.8 9.0), submucosal invasion (2.0; 1.1 - 3.4) and location of upper/middle (1.9; 1.0 - 3.6); Group B: size > 20 mm (3.0; 1.6 - 5.5), undifferentiated-type (3.0; 1.1 - 8.0) and location of upper/middle (2.4; 1.2 - 4.8). CONCLUSIONS: Endoscopists must be aware of these factors associated with incomplete gastric ESD due to misdiagnosis to further decrease their incidence. PMID- 27556099 TI - Endoscopic restoration of the esophagus. PMID- 27556100 TI - Peroral endoscopic pyloromyotomy accelerates gastric emptying in healthy pigs: proof of concept. AB - INTRODUCTION: Gastroparesis, or delayed gastric emptying, can be diagnosed with gastric emptying scintigraphy. Manometric studies of patients with gastroparesis show increased pyloric tone (pylorospasm). Among the recent endoscopic therapies for pylorospasm is peroral endoscopic pylorotomy (POP). In this study, we explored the effect of POP on gastric emptying in healthy pigs. MATERIAL AND METHODS: Four mini-pigs underwent POP following general anaesthesia. The mucosal entrance was situated 5 cm above the pylorus. POP was performed through a submucosal tunnel dissection. The duration of gastric emptying was assessed by scintigraphy before and after the procedure. The pigs were then euthanised for necropsy and pathologic assessment of the pylorus. RESULTS: The mean duration of the procedure was 55 (+/- 4 SD) min. All surgeries were performed in their entirety with 100 % feasibility. There were no cases of bleeding. The one case of perforation had no clinical significance. The duration of gastric emptying was 2.22-fold shorter after POP compared with before POP (T1/2 post-POP = 84.5 [+/- 35.7 SD] min vs. T1/2 pre-POP = 188.4 [+/- 87.3 SD] min; P = 0.029). In agreement with the endoscopic observations, sectioning of the pyloric muscle in each pig was histologically complete. CONCLUSION: The efficacy of the procedure provides indirect proof of the involvement of the pyloric ring in delayed gastric emptying and suggests new therapies for patients with gastroparesis. Our protocol combining gastric emptying scintigraphy and POP validated the use of anaesthetised mini-pigs as a learning and training model for POP or other endoscopic/surgical procedures related to gastric emptying. PMID- 27556101 TI - Linked color imaging improves endoscopic diagnosis of active Helicobacter pylori infection. AB - BACKGROUND AND STUDY AIMS: Linked color imaging (LCI) is a new image-enhanced endoscopy technique using a laser light source to enhance slight differences in mucosal color. The aim of this study was to compare the usefulness of LCI and conventional white light imaging (WLI) endoscopy for diagnosing Helicobacter pylori (H. pylori). PATIENTS AND METHODS: We retrospectively analyzed images from 60 patients examined with WLI and LCI endoscopy between October 2013 and May 2014. Thirty patients had H. pylori infections, and other thirty patients tested negative for H. pylori after eradication therapy. Four endoscopists evaluated the 2 types of images to determine which was better at facilitating a diagnosis of H. pylori infection. RESULTS: H. pylori infection was identified with LCI by enhancing the red appearance of the fundic gland mucosa. The accuracy, sensitivity, and specificity for diagnosing H. pylori infection using WLI were 74.2 %, 81.7 %, and 66.7 %, respectively, while those for LCI were 85.8 %, 93.3 %, and 78.3 %, respectively. Thus, the accuracy and sensitivity for LCI were significantly higher than those for WLI (P = 0.002 and P = 0.011, respectively). The kappa values for the inter- and intraobserver variability among the 4 endoscopists were higher for LCI than for WLI. CONCLUSIONS: H. pylori infection can be identified by enhancing endoscopic images of the diffuse redness of the fundic gland using LCI. LCI is a novel image-enhanced endoscopy and is more useful for diagnosing H. pylori infection than is WLI. PMID- 27556102 TI - Clinical features of gallstone impaction at the ampulla of Vater and the effectiveness of endoscopic biliary drainage without papillotomy. AB - BACKGROUND AND STUDY AIMS: Gallstone impaction at the ampulla of Vater is a critical condition, and the standard treatment is endoscopic papillotomy. However, the clinical features remain largely unclear, and some patients are reluctant to undergo papillotomy because of a bleeding tendency. The aim of this study was to clarify the clinical features of gallstone impaction at the ampulla of Vater and to examine the effectiveness of endoscopic biliary drainage without papillotomy. PATIENTS AND METHODS: We retrospectively examined 30 patients who had undergone endoscopic treatment for gallstone impaction at the ampulla of Vater between 2010 and 2015. RESULTS: According to the severity classification for acute cholangitis in the Tokyo Guidelines (TG13), the condition was mild in 8 patients, moderate in 14, and severe in only 8 (27 %), despite the stone impaction at the ampulla of Vater. Hyperamylasemia was observed in 18 patients (60 %); computed tomography (CT) revealed clear pancreatitis in 5 cases (17 %). Patients were classified into Group A (13 patients who received biliary drainage with papillotomy) and Group B (17 patients receiving biliary drainage without papillotomy). All patients in Group B had 1 or more types of hemorrhage risk. There were no differences between the 2 groups in the success rate of biliary drainage, the rate of elevated serum amylase the following day, or procedure related complications. Serum amylase levels decreased the following day in all patients, even in Group B (including the 10 patients with hyperamylasemia and the 3 patients with clear pancreatitis on CT). CONCLUSIONS: Even with stone impaction at the ampulla of Vater, typical clinical features of cholangitis and pancreatitis are relatively rare. Biliary drainage without papillotomy is acceptable for gallstone impaction at the ampulla of Vater. PMID- 27556103 TI - Interobserver agreement among cytopathologists in the evaluation of pancreatic endoscopic ultrasound-guided fine needle aspiration cytology specimens. AB - BACKGROUND AND AIMS: Endoscopic ultrasound with fine needle aspiration (EUS-FNA) has become the standard of care in the evaluation of solid pancreatic lesions. Limited data exist on interobserver agreement (IOA) among cytopathologists in assessing solid pancreatic EUS-FNA specimens. This study aimed to evaluate IOA among cytopathologists in assessing EUS-FNA cytology specimens of solid pancreatic lesions using a novel standardized scoring system and to assess individual clinical and cytologic predictors of IOA. METHODS: Consecutive patients who underwent EUS-FNA of solid pancreatic lesions at a tertiary care referral center were included. EUS-FNA slides were evaluated by four blinded cytopathologists using a standardized scoring system that assessed final cytologic diagnosis and quantitative (number of nucleated/diagnostic cells) and qualitative (bloodiness, inflammation/necrosis, contamination, artifact) cytologic parameters. Final clinical diagnosis was based on final cytology, surgical pathology, or 1-year clinical follow-up. IOA was calculated using multi rater kappa (kappa) statistics. Bivariate analyses were performed comparing cases with and without uniform agreement among the cytopathologists followed by logistic regression with backward elimination to model likelihood of uniform agreement. RESULTS: Ninety-nine patients were included (49 % males, mean age 64 years, mean lesion size 26 mm). IOA for final diagnosis was moderate (kappa = 0.45, 95 % confidence interval (CI) 0.4 - 0.49) with minimal improvement when combining suspicious and malignant diagnoses (kappa = 0.54, 95 %CI 0.49 - 0.6). The weighted kappa value for overall diagnosis was 0.65 (95 %CI 0.54 - 0.76). IOA was slight to fair (kappa = 0.04 - 0.32) for individual cytologic parameters. A final clinical diagnosis of malignancy was the most significant predictor of agreement [OR 3.99 (CI 1.52 - 10.49)]. CONCLUSIONS: Interobserver agreement among cytopathologists for pancreatic EUS-FNA specimens is moderate-substantial for the final cytologic diagnosis. The final clinical diagnosis of malignancy was the strongest predictor of agreement. These results have significant implications for patient management and need to be validated in future trials. PMID- 27556104 TI - Bowel preparation in pediatric colonoscopy: results of an open observational study. AB - BACKGROUND AND STUDY AIMS: The goal of this study was to analyze the bowel cleansing methods currently used for pediatric colonoscopy in terms of effectiveness, tolerance and safety. PATIENTS AND METHODS: Data from 768 colonoscopies reported by 28 centers were registered in an online database for further analysis. Binary logistic regression was used to determine how preparation methods affected the cleaning effect (Aronchick score) and the rate of adverse events (Aes) and complications. RESULTS: The most frequently reported cleansing agents were sodium picosulphate (54.2 %) and polyethylene-glycol (41.3 %) in various combinations. The cleaning effect was good to excellent in 72.6 % of patients. AEs during the preparation period occurred in 21.5 % of patients. Complications during endoscopy were reported in 12.1 % and were mostly mild. The different agents had no influence on the cleaning effect. In contrast the risk of AEs during preparation was significantly increased when polyethylene-glycol was used (odds ratio (OR) 2.112, P = 0.002) but reduced with the use of sodium picosulphate (OR 0.380, P < 0.001). In particular, the risk of needing a nasogastric tube to complete clean-out was about 10-fold higher when polyethylene glycol was used. CONCLUSIONS: A large variety of regimens are used for bowel preparation in children. We found a good overall cleaning result independent of the agents used. Cleansing agents, on the other hand, had a significant influence on tolerance and safety. PMID- 27556105 TI - Recombinant mumps virus as a cancer therapeutic agent. AB - Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21(st) century, the interest to pursue mumps virus for cancer treatment slowly faded away. Recent success stories of oncolytic clinical trials prompted us to resurrect the mumps virus and to explore its potential for cancer treatment. We have obtained the Urabe strain of mumps virus from Osaka University, Japan, which was used in the earlier human clinical trials. In this report we describe the development of a reverse genetics system from a major isolate of this Urabe strain mumps virus stock, and the construction and characterization of several recombinant mumps viruses with additional transgenes. We present initial data demonstrating these recombinant mumps viruses have oncolytic activity against tumor cell lines in vitro and some efficacy in preliminary pilot animal tumor models. PMID- 27556106 TI - N-end rule pathway inhibition assists colon tumor regression via necroptosis. AB - Recent study has shown that N-end rule pathway, an ubiquitin dependent proteolytic system, counteracts cell death by degrading many antisurvival protein fragments like BCLxL, BRCA1, RIPK1, etc. Inhibition of the N-end rule pathway can lead to metabolic stabilization of proapoptotic protein fragments like RIPK1, thereby sensitizing cells to programmed cell death. Receptor interacting serine threonine protein kinase-1 (RIPK1) is one of the upstream regulators of programmed necrosis known as necroptosis. Necroptosis is particularly gaining attention of cancer biologists as it provides an alternate therapeutic modality to kill cancer cells, which often evolve multiple strategies to circumvent growth inhibition by apoptosis. Utilizing the over expression of biotin receptor in cancer cells, herein, we report that coadministration of synthetic hetero bivalent N-end rule inhibitor RFC11 and anticancer drug shikonin solubilized in a stable biotin receptor-targeted liposome exhibited significant synergistic antitumor effect in both subcutaneous and orthotopic mouse colon tumor model through induction of necroptosis with distinctive upregulation of RIPK1. Besides developing a newly targeted formulation for necroptosis induction, this report is the first in vivo evidence demonstrating that potent inhibition of N-end rule pathway can enhance therapeutic efficacy of conventional chemotherapeutics. PMID- 27556107 TI - Editorial. AB - no summary. PMID- 27556108 TI - Polish project of a Sex Offenders Registry - a mental health professionals' perspective. AB - The paper discusses the governmental draft of the Act on counteracting threats of sexual offences. It assumes the creation of the Registry of Sex Offenders in a version with a limited access and a version available to the public. The registry is supplemented with a publically available map of sexual crime threats, which includes the places of sexual offences and the places of residence of offenders. Criticising the proposed solutions, the authors point out the lack of integration with other interventions conducted in Poland against sex offenders, noncompliance with the recommendations of the most important expert circles in the field, as well as the research results showing the lack of effectiveness of the planned measures to reduce sexual offences. Anumber of negative consequences of making the sex offenders'data available to the public was also highlighted in the form of a clear deterioration of social rehabilitation prognoses, additional stigmatisation, as well as social exclusion of the offenders themselves and the victims of sexual violence. The summary emphasises the need to counteract the problem of sexual offences in a systematic way and the need to diversify the interventions undertaken against the offenders, depending on the level of risk of sexual recidivism. PMID- 27556109 TI - Nonspecific eating disorders - a subjective review. AB - AIM: The aim of this paper was to characterise nonspecific eating disorders (other than anorexia nervosa and bulimia nervosa). METHOD: The Medline database was searched for articles on nonspecific eating disorders. The following disorders were described: binge eating disorder (BED), pica, rumination disorder, avoidant/restrictive food intake disorder, night eating syndrome (NES), sleep related eating disorder (SRED), bigorexia, orthorexia, focusing on diagnosis, symptoms, assessment, comorbidities, clinical implications and treatment. RESULTS: All of the included disorders may have dangerous consequences, both somatic and psychological. They are often comorbid with other psychiatric disorders. Approximately a few percent of general population can be diagnosed with each disorder, from 0.5-4.7% (SRED) to about 7% (orthorexia). With the growing literature on the subject and changes in DSM-5, clinicians recognise and treat those disorders more often. CONCLUSIONS: More studies have to be conducted in order to differentiate disorders and treat or prevent them appropriately. PMID- 27556110 TI - Bone mineralization disorders as a complication of anorexia nervosa - etiology, prevalence, course and treatment. AB - Anorexia nervosa (AN) most often has its onset in adolescence, which is a crucial period to achieve peak bone mass. The hormonal abnormalities (hypoestrogenism, hypercortisolism, decreased secretion of dehydroepiandrosterone, testosterone, insulin-like growth factor) and malnutrition are associated with profound bone mineralization disorders. Densitomertic bone mineral density (BMD) values for osteopenia and osteoporosis were found respectively in 35-98% and 13-50% of women with AN. Prospective studies indicate a further decline in BMD at the beginning of treatment and a crucial importance of weight gain and return of spontaneous menses for its growth. Due to frequent chronic and relapsing course of AN densitometric assessment of BMD is recommended in all patients with AN and amenorrhea lasting around twelve months. In order to establish standards for the treatment of osteoporosis in AN, studies on pharmacological treatment are conducted. There are promising results indicating the improvement in BMD after treatment with physiologic oestrogen replacement treatment and sequential administration of medroxyprogesterone in teenage girls and bisphosphonates in adult women. Supplementation of vitamin D and adequate consumption of calcium from diet are recommended. Further studies on the effectiveness of long-term treatment of osteoporosis with regard to the possibility of increase in BMD and reducing the risk of osteoporotic fractures are needed. PMID- 27556111 TI - Changes in oral cavity during period of intensive vomiting in patient with somatoform autonomic dysfunction - description of the case. AB - INTRODUCTION: The most important endogenous causes of erosion are eating disorders, gastro-oesophageal reflux (GERD), alcoholism and syndromes involving lowered saliva secretion. AIM: The aim of this work is to study a patient with symptoms of somatoform autonomic dysfunction, in which significant erosive loss occurred through chemical influence of gastric acid on oral cavity. METHODS: Seventeen years old girl was sent to Department of Child and Adolescent Psychiatry due to persistent nausea and vomiting, which occurred over a period of about 10 months. Because of this she was repeatedly admitted to a paediatric hospital. Nausea and vomiting led to fear of going out of the house and of being in public places. In addition dental clinical examination was performed. RESULTS: Somatoform Disorders, during which there has been intense vomiting, can be seen as an unusual example of purging-type eating disorders. Erosion of enamel was the most common. In examination of oral mucosa, keratinisation, tongue covered with removable coating and exfoliative cheilitis associated with drying and cracking of lips, were detected. CONCLUSIONS: Observed erosion of teeth and changes in macroscopic construction of oral mucosa seem to be symptoms caused mainly by induced intense and prolonged vomiting. Those changes may be a serious problem not only for the patient's health but also their aesthetics. The described case of patient with intense and long-term vomiting indicates the need of multidisciplinary medical care, including systematic dental assessment. PMID- 27556112 TI - Impaired social cognition processes in Asperger syndrome and anorexia nervosa. In search for endophenotypes of social cognition. AB - A growing number of publications indicates presence of significant deficits in social cognition in patients with anorexia nervosa (AN). These deficits appear to be comparable in qualitative and quantitative dimension with impairment of the same functions among people with Asperger syndrome (AS). The aim of this study is to identify subject areas in the field of impairment of social cognition processes among people with Asperger syndrome and anorexia nervosa taking into consideration the potential contribution of genetic pathways of oxytocin and vasopressin in the pathogenesis of these diseases. In the first part of the paper a systematic analysis of studies aimed at the evaluation of the processes of social cognition among patients with AN and AS has been carried out. The results of a significant number of studies confirm the presence of deficits in social cognition in AN and AS. In addition, among patients with AN and AS there exists a similar structure and distribution of the brain functions in regions responsible for social cognition. The second part of the paper describes the role of the oxytocin-vasopressin system (OT-AVP) in the processes of social cognition in AN and AS. Its genetic basis and the possible importance of single nucleotide polymorphisms within the genes: OXT, AVP, CD38, OXTR, AVPR1A and LNPEP have also been presented. PMID- 27556114 TI - Prevalence and consequences of insomnia in pediatric population. AB - Insomnia presents an increasing and significant health issue in paediatric population. As the problem had grown over past decade, it became recognised by the specialists dealing with children and adolescents. In a recent study American Academy of Child and Adolescent Psychiatry members were asked about their experience with patients complaining about sleep disturbances. Doctors reported that sleep was a problem for 1/3 of their patients out of which 1/4 required pharmacotherapy [1]. Multiple studies concerning adults confirmed significance of healthy sleep in optimal cognitive, emotional, social and biological functioning. Adequate sleep is important in prophylaxis of many chronic diseases such as obesity, diabetes, hypertension, myocardial infarction, stroke [2]. Due to increasing prevalence of insomnia in children and adolescents growing attention is paid to its short and long term consequences in this group. This review summarises available data on chronic insomnia prevalence and its consequences in population under 18 years old. PMID- 27556113 TI - The role of genetic factors and pre- and perinatal influences in the etiology of autism spectrum disorders - indications for genetic referral. AB - Autism spectrum disorders (ASD) are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system - oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders - intellectual disability, epilepsy and dysmorphias - a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases. PMID- 27556115 TI - Treatment of behavioral sleep problems in children and adolescents - literature review. AB - AIM: To collect data on treatment of behavioural sleep disorders in children and adolescents. MATERIALS AND METHODS: A literature review based on the PUBMED database. RESULTS: Based on the analysed materials three basic complementary procedures were identified - implementation of sleep hygiene, behavioural interventions and pharmacological treatment. The rules of sleep hygiene proven to be effective include: regular sleep schedule, adequately prepared place to sleep (a dark, quiet bedroom without multimedia), bedtime routine, avoiding caffeinated beverages. The following issues require further studies to confirm their effectiveness: falling asleep independently without parent's assistance, bedtime reading, physical activity, reducing daytime multimedia use, tryptophan rich breakfasts. Behavioural interventions and pharmacological treatment may in some cases be temporarily implemented to complement the sleep hygiene. CONCLUSIONS: The implementation of sleep hygiene is a primary, fully acceptable to the child and parents, way to improve the baby sleep. In case of ineffectiveness of the proposed rules, those can be complemented with behavioural methods that are highly effective but some parents do not accept them or make mistakes in their introduction. Pharmacotherapy can be used as a temporary support for families with severe behavioural problems as an aid in the implementation of sleep hygiene and behavioural methods. PMID- 27556116 TI - The application of computer assisted technologies (CAT) in the rehabilitation of cognitive functions in psychiatric disorders of childhood and adolescence. AB - First applications of computer-assisted technologies (CAT) in the rehabilitation of cognitive deficits, including child and adolescent psychiatric disorders date back to the 80's last century. Recent developments in computer technologies, wide access to the Internet and vast expansion of electronic devices resulted in dynamic increase in therapeutic software as well as supporting devices. The aim of computer assisted technologies is the improvement in the comfort and quality of life as well as the rehabilitation of impaired functions. The goal of the article is the presentation of most common computer-assisted technologies used in the therapy of children and adolescents with cognitive deficits as well as the literature review of their effectiveness including the challenges and limitations in regard to the implementation of such interventions. PMID- 27556117 TI - Characteristics of mentalization patterns in parents of children with difficulties in realizing developmental objectives of the latency stage - qualitative analysis results. AB - OBJECTIVES: The aim of the study was to answer the question about the ability to mentalize emotional states in parents of children with difficulties in realizing developmental objectives of the latency stage. The research was exploratory in nature; the aim was formulated on the basis of notions from the field literature indicating a correlation between the attachment style and the ability to mentalize in the parents and psychosocial functioning of their children. METHODS: The structured Adult Attachment Interview (AAI) was used as the main tool for the research. The analysis was performed with the Reflective Functioning Scale. Total of 9 narrations obtained through AAI were subjected to qualitative analysis. RESULTS: The conducted analysis showed that parents of children with difficulties in realizing developmental objectives of the latency stage are characterized by reduced mentalization skills. The mentalization pattern isolated in the analysis, characteristic for the studied group encompasses the tendency towards idealization, generalization, describing the relation at the behavioural level and avoidance of reflecting upon mental states experienced in the context of early attachment relations, and the lack of coherence. Difficulties in mentalization of relationships mainly concern the relation with the mother. Relations established later in life are better mentalized than the early relations with parents. CONCLUSIONS: Observed disturbance in mentalization may suggest possible disturbances in the process of reflecting and containing in the early developmental stages of the examined persons. Mentalization skills were developed later in life of the examined persons. Idealization turned out to be the process that is most impacting and interfering with free reflections upon one's own emotions and emotions of the others (including those of one's own child). PMID- 27556118 TI - Family therapy process - works on the Polish version of SCORE-15 tool. AB - OBJECTIVES: The aim of the paper is to demonstrate progress of the works on the Polish version of SCORE-15 and the results of the preliminary data analysis of changes in the process of family therapy, obtained with this tool. The works on the Polish version, ongoing since 2010, were inspired by the Research Committee European Family Therapy Association EFTA. Since the Polish version of SCORE-15 will be make public and published on EFTA website in the near future, therefore, it is important that people interested in the tool know the context of its development. METHODS: The Polish version of SCORE-15, the tool designed to examine the process of family therapy, was used. RESULTS: The comparison of the results obtained by family members before the first family session and before the fourth one and psychotherapists' assessments show that the perception of the weight of the problem with which the family members came to therapy is indeed significantly lower already after three sessions of family therapy. Additionally, the obtained results show great coherence of the assessment of the family therapy progress in families and their therapists. CONCLUSIONS: The preliminary analysis of data obtained during the research project conducted in Outpatient Family Therapy Clinic, Department of Adult, Child and Adolescent Psychiatry, University Hospital in Krakow and in Laboratory of Psychology and Systemic Psychotherapy, Department of Child and Adolescent Psychiatry, Jagiellonian University Medical College between 2010 and 2014 revealed that SCORE-15 is a useful tool in research on changes in the systemic family therapy process. PMID- 27556119 TI - Mechanisms shaping the development of personality and personality disorders in children and adolescents. AB - Until the end of the nineties last century personality disorders could not be diagnosed before the age of eighteen. Nevertheless, the results of studies published in the last decade have revealed that personality disorders can be observed in children and adolescents and that personality disorders diagnosed in adult patients had been present as early as in childhood. The knowledge of possible mechanisms shaping personality disorders in childhood is unsatisfactory and needs to be expanded. Developmental psychology explains the development of abnormal personality through inappropriate attachment patterns and abnormal transitions between developmental phases. Genetic and temperamental factors are also important in the aetiology of personality disorders as well as early maladaptive schemas resulting from personal experiences and interactions with others. The aim of this article is to review the current knowledge on the mechanisms shaping the development of personality and personality disorders in childhood and adolescence. PMID- 27556120 TI - Prevalence and risk factors of depressive episodes among student population in Wroclaw - epidemiological study results. AB - OBJECTIVES: The aim of this study was to identify risk factors and estimate prevalence of depressive episodes among Wroclaw's universities students. METHODS: Polish adaptation of the Composite International Diagnostic Interview (CIDI) was implemented to gather epidemiological data from 370 students of public universities in Wroclaw. Proportional stratified sampling was performed to obtain distinct, independent strata representing sex, year of study and educational profiles. Randomisation was ensured by recruitment procedures. RESULTS: Prevalence of depressive episodes among students in Wroclaw is high - 14.7% throughout life, 9.8% within 12 months prior to the interview. High prevalence of severe and moderate depressive episodes seems to be worrisome (respectively 5.1% and 6.6% throughout life, 3.8% and 3.9% within 12 months prior to the study). Year of study, profile and lack of partner relationship remain risk factor for depression. CONCLUSIONS: High prevalence of depressive episodes indicates the need for prevention and therapy based on epidemiological data and tailored to the students' needs. Depression among students requires further epidemiological studies. PMID- 27556121 TI - Letter to Editors. Upon the bill on prevention of sexual delinquency threats. PMID- 27556122 TI - Letter to Editor. Who should reach for psychotherapy ? PMID- 27556123 TI - Letter to Editor. Polish text with information for the patientand the form of the informed consent for electroconvulsive treatment. PMID- 27556124 TI - Letter to Editor. Report "An investigation of the 'female camouflage effect' in autism using a new computerized test showing sex/gender differences during ADOS 2". IMFAR 2016, Baltimore, USA. PMID- 27556125 TI - Preface. PMID- 27556126 TI - Response. PMID- 27556127 TI - Response. PMID- 27556128 TI - Immunology: JAK3 inhibition-is it sufficient? PMID- 27556129 TI - Not Available. PMID- 27556130 TI - Bioplastic hydroxyl radical trapping. PMID- 27556131 TI - Corrigendum to "Prenatal valproic acid exposure disrupts tonotopic c-Fos expression in the rat brainstem" [Neuroscience 311 (2015) 349-361]. PMID- 27556132 TI - Preface. PMID- 27556133 TI - Author Reply. PMID- 27556134 TI - Author Reply. PMID- 27556135 TI - Re-making the system: founding an inspirational model for humanitarian aid: An interview with Drs Vincent Leung and KL Cheung. PMID- 27556136 TI - The mobile X-ray machine. PMID- 27556137 TI - Summer-Safe, Trauma-Wise: Advocating for Preventative Legislation. PMID- 27556138 TI - Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity. AB - New catechol-containing chemical entities have been investigated as matrix metalloproteinase inhibitors as well as antioxidant molecules. The combination of the two properties could represent a useful feature due to the potential application in all the pathological processes characterized by increased proteolytic activity and radical oxygen species (ROS) production, such as inflammation and photoaging. A series of catechol-based molecules were synthesized and tested for both proteolytic and oxidative inhibitory activity, and the detailed binding mode was assessed by crystal structure determination of the complex between a catechol derivative and the matrix metalloproteinase-8. Surprisingly, X-ray structure reveals that the catechol oxygens do not coordinates the zinc atom. PMID- 27556139 TI - Evaluating the clinical utility of the Validity-10 for detecting amplified symptom reporting for patients with mild traumatic brain injury and comorbid psychological health conditions. AB - The objective of this study was to compare the Validity-10 scale with the PAI Negative Impression Management Scale (PAI-NIM) for detecting exaggerated symptom reporting in active-duty military service members (SMs) admitted with unremitting mild TBI symptoms and comorbid psychological health conditions (mTBI/PH). Data were analyzed from 254 SMs who completed the Neurobehavioral Symptom Inventory (NSI) and Personality Assessment Inventory (PAI) as a part of a larger battery of self-report symptom scales upon admission to the intensive-outpatient TBI treatment program at a military medical center. Symptom exaggeration was operationalized using the PAI Negative Impression Management Scale (PAI-NIM). A PAI-NIM score of >=73 was categorized as positive for symptom exaggeration (SVTpos), while a lower score was categorized as negative for symptom exaggeration (SVTneg). SMs in the SVTpos group (n = 34) had significantly higher scores (p <= .004) on the PAI clinical scales as well as on the NSI total score (range: d = 0.59-1.91) compared to those who were SVTneg (n = 220). The optimal cut-score for the NSI Val-10 scale to identify possible symptom exaggeration was >=26 (sensitivity = .29, specificity = .95, PPP = .74, NPP = .71). In patients suffering from mTBI/PH, the Validity-10 requires a higher cut-score than previously reported to be useful as a metric of exaggerated symptom reporting. PMID- 27556140 TI - Interfacial Diffusion and Bonding in Multilayer Polymer Films: A Molecular Dynamics Simulation. AB - As a stacked form of ultrathin polymer films, multilayer nanostructures are of great interest in various applications. Coarse-grained molecular dynamics simulations were carried out to understand the behaviors of interfacial diffusion and bonding of multilayer polymer films. We found two obvious stages for the interfacial diffusion of polymers in the multilayer film, and it is 3 times faster in the first stage than in the second one due to the evolution of molecular conformations. The polymers near the interfaces have an in-plane mobility much higher than the out-of-plane one. The strength of interfacial bonding has been characterized by the fast tensile stress-strain curve along the normal direction. It shows multiple yielding points for the multilayer polymer films, which is distinct from the tensile behavior of the bulk. The ultimate tensile stress (UTS) and corresponding separating strain, surprisingly, do not necessarily increase with diffusion time. Because of the dramatic molecular rotation and extension during the first stage of interfacial diffusion, the interlayer interpenetration is nonuniformly distributed in the plane of the interface. Such a nonuniform distribution may be one of the reasons for the decrease of the UTS and separating strain. PMID- 27556141 TI - Cross Section of OH Radical Overtone Transition near 7028 cm(-1) and Measurement of the Rate Constant of the Reaction of OH with HO2 Radicals. AB - The absorption cross section of an overtone transition of OH radicals at 7028.831 cm(-1) has been measured using an improved experimental setup coupling laser photolysis to three individual time-resolved detection techniques. Time-resolved relative OH radical profiles were measured by laser-induced fluorescence (LIF), and their absolute profiles have been obtained by cw-cavity ring-down spectroscopy (cw-CRDS). HO2 radicals were quantified simultaneously at the well characterized absorption line at 6638.21 cm(-1) by a second cw-CRDS absorption path. Initial OH concentrations and thus their absorption cross sections have been deduced from experiments of 248 nm photolysis of H2O2: OH and HO2 profiles have been fitted to a simple kinetic model using well-known rate constants. The rate constant of the reaction between OH and HO2 radicals turned out to be sensitive to the deduction of the initial OH concentration and has been revisited in this work: OH decays have been observed in the presence of varying excess HO2 concentrations. A rate constant of (1.02 +/- 0.06) * 10(-10) cm(3) s(-1) has been obtained, in good agreement with previous measurements and recent recommendations. An absorption cross section of sigmaOH = (1.54 +/- 0.1) * 10( 19) cm(2) at a total pressure of 50 Torr helium has been obtained from consistent fitting of OH and HO2 profiles in a large range of concentrations. PMID- 27556142 TI - Inhaled Desmopressin for Refractory Gastrointestinal Bleeding in a Patient With a HeartMate II Left Ventricular Assist Device. AB - Patients with a durable, continuous-flow left ventricular assist device (LVAD) are commonly prescribed the combination of an oral anticoagulant and an oral antiplatelet agent as prophylaxis against device thrombosis and systemic embolic events. Current International Society of Heart and Lung (ISHLT) guidelines recommend warfarin with an INR goal of 2-3 and concomitant aspirin 81-325 mg daily for patients with a HeartMate II LVAD. Unfortunately, gastrointestinal (GI) bleeding is very common in these patients because of multiple factors including the development of arteriovenous malformations and acquired von Willebrand syndrome. If this bleeding cannot be corrected through interventional measures, it then requires at least temporary, and potentially permanent, cessation of antiplatelet or anticoagulant therapy. Patients who continue to bleed while off all antithrombotic therapies present a clinical challenge. We describe the successful management of a patient with refractory GI bleeding through the use of inhaled desmopressin. PMID- 27556143 TI - Extracorporeal Left Ventricular Circulatory Support as a Bridge to Implantable LVAD for a Patient With Pan-Left Ventricular Thrombosis. AB - We present the case of a 57 year old woman who developed pan-left ventricular thrombus while being supported with central extracorporeal membrane oxygenation support for cardiogenic shock. The left heart thrombus was evacuated emergently through the aortic valve, left atriotomy, and left ventriculotomy. The cannulation was then revised with the addition of a 36 French angled cannula in the apex of the left ventricle to decompress the ventricle, minimize stasis, and allow for any residual microthrombus to be trapped in the oxygenator membrane, not causing embolization. Once her neurological status was confirmed intact, a durable device was implanted. She recovered well without any neurological injury. PMID- 27556144 TI - Numerical and In Vitro Experimental Investigation of the Hemolytic Performance at the Off-Design Point of an Axial Ventricular Assist Pump. AB - The ventricular assist pumps do not always function at the design point; instead, these pumps may operate at unfavorable off-design points. For example, the axial ventricular assist pump FW-2, in which the design point is 5 L/min flow rate against 100 mm Hg pressure increase at 8,000 rpm, sometimes works at off-design flow rates of 1 to 4 L/min. The hemolytic performance of the FW-2 at both the design point and at off-design points was estimated numerically and tested in vitro. Flow characteristics in the pump were numerically simulated and analyzed with special attention paid to the scalar sheer stress and exposure time. An in vitro hemolysis test was conducted to verify the numerical results. The simulation results showed that the scalar shear stress in the rotor region at the 1 L/min off-design point was 70% greater than at the 5 L/min design point. The hemolysis index at the 1 L/min off-design point was 3.6 times greater than at the 5 L/min design point. The in vitro results showed that the normalized index of hemolysis increased from 0.017 g/100 L at the 5 L/min design point to 0.162 g/100 L at the 1 L/min off-design point. The hemolysis comparison between the different blood pump flow rates will be helpful for future pump design point selection and will guide the usage of ventricular assist pumps. The hemolytic performance of the blood pump at the working point in the clinic should receive more focus. PMID- 27556146 TI - The Pathophysiology of Nitrogen Dioxide During Inhaled Nitric Oxide Therapy. AB - Administration of inhaled nitric oxide (NO) with the existing compressed gas delivery systems is associated with unavoidable codelivery of nitrogen dioxide (NO2), an unwanted toxic contaminant that forms when mixed with oxygen. The NO2 is generated when NO is diluted with O2-enriched air before delivery to the patient. When NO2 is inhaled by the patient, it oxidizes protective antioxidants within the epithelial lining fluid (ELF) and triggers extracellular damage in the airways. The reaction of NO2 within the ELF triggers oxidative stress (OS), possibly leading to edema, bronchoconstriction, and a reduced forced expiratory volume in 1 second. Nitrogen dioxide has been shown to have deleterious effects on the airways of high-risk patients including neonates, patients with respiratory and heart failure, and the elderly. Minimizing co-delivery of NO2 for the next generation delivery systems will be a necessity to fully optimize the pulmonary perfusion of NO because of vasodilation, whereas minimizing the negative ventilatory and histopathological effects of NO2 exposure during inhaled NO therapy. PMID- 27556147 TI - Percutaneous Dilatation Tracheostomy in Patients with Left Ventricular Assist Device and Established Phenprocoumon Therapy. AB - Over the last decade, the number of heart transplantations declined, and the number of implanted left ventricular assist devices (LVADs) markedly increased. Accordingly, common intensive care interventions rise and present their own challenges, especially because of the necessary anticoagulation regimen. One of these procedures is percutaneous dilatation tracheostomy (PDT). We herein report our experience with 34 patients with LVAD and established phenprocoumon therapy (International normalized ratio 2.1 +/- 0.9, partial thromboplastin time 68.9 +/- 19.0 seconds) who underwent PDT between 2006 and 2015 at our specialized cardiac surgery intensive care unit. Intraprocedural success was achieved in all cases (34/34 patients) with sufficient placement of the tracheal tube and adequate mechanical ventilation. No retained secretions or tracheostomy tube obstructions were observed during follow-up. In no case, conversion to surgical tracheostomy was necessary. No serious bleeding complications that required urgent or emergent reoperation occurred during or after the PDT procedure. A total of 16 patients (47.1%) died within the first 30 days after LVAD implantation. This is the first report describing outcomes of patients with LVAD under established phenprocoumon therapy and postoperative implemented PDT. PDT is a safe procedure for those patients. It is not connected with bleeding complications and shows a good procedural outcome. PMID- 27556148 TI - The "Central Sport Model": Extracorporeal Membrane Oxygenation Using the Innominate Artery for Smaller Patients as Bridge to Lung Transplantation. AB - Venoarterial extracorporeal membrane oxygenation (VA ECMO) may be used in patients with advanced cardiac or pulmonary failure. Arterial cannulation via the femoral arteries is suboptimal in many clinical scenarios because of associated complications and the potential for differential hypoxemia between the upper and lower body. To address these concerns, we typically use an upper body configuration (sport model) with right internal jugular and axillary or subclavian artery cannulation to allow a safe and durable means of providing VA ECMO support without differential hypoxemia. Unfortunately, this approach may not be feasible in smaller patients, whose vessels may preclude optimal use of the axillary or subclavian arteries and in those with systemic vasculopathy associated with connective tissue disorders. We describe a new approach for patients of small stature using the innominate artery through a mini-upper sternotomy in seven patients. PMID- 27556149 TI - Systemic Thrombolysis Is an Alternative Therapeutic Option for Pump Thrombosis with Acceptable Risks. PMID- 27556150 TI - Outcomes of Adult Patients with Small Body Size Supported with a Continuous-Flow Left Ventricular Assist Device. AB - There is insufficient data on patients with small body size to determine if this should be considered a risk factor for continuous-flow left ventricular assist device (CF-LVAD) support. We sought to evaluate survival outcomes, adverse events, and functional status of CF-LVAD patients with body surface area (BSA) <1.5 m in a large national registry. Adults with BSA < 1.5 m (n = 128) implanted with a HeartMate II (HMII)-LVAD from the Interagency Registry for Mechanically Assisted Circulatory Support registry from April 2008 to December 2012 formed this cohort. Outcomes were compared with HMII bridge to transplant (BTT) and destination therapy (DT) post approval studies. The majority of patients were female (n = 106, 83%). A total of 64% (n = 82) were implanted for BTT and 36% (n = 46) for DT. The median BSA (range) was 1.44 (1.19-1.49) and 1.45 (1.25-1.49) m for BTT and DT, respectively. Overall survival 1 year post implant was 81% +/- 5% for BTT and 84% +/- 6% for DT. The most common adverse events for BTT and DT patients were bleeding (0.91, 0.88 events/patient year) and driveline infection (16%, 0.28 events/patient year). Six months post implantation, 87% of BTT and 77% of DT patients were New York Heart Association functional class I or II. Post implant survival, functional status improvement, and adverse event profile for adult BTT and DT HMII patients with BSA < 1.5 m are favorable and comparable with outcomes published in the overall patient population. PMID- 27556151 TI - Systemic Thrombolysis Can Be a Therapy Option Only in Highly Selected Cases of Pump Thrombosis. PMID- 27556152 TI - Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device. AB - Efficacious ventricular assist device (VAD) support in pediatric patients depends on successful antithrombotic management. The experience with antithrombotic management for the EXCOR Pediatric VAD Investigational Device Exemption (IDE) study is described. All 68 children in North America enrolled in the IDE study from May 9, 2007 to December 10, 2010 are included. The Edmonton Anticoagulation and Platelet Inhibition Protocol was provided for management guidance. Monitoring parameters, drug dosing, targeted serious adverse events, and pump changes were reviewed. Major bleeding occurred in 43% of all subjects with most events occurring within 14 days of implantation. Bleeding events were probably/definitely related in 24% to antithrombotic management. Neurologic events occurred in 28% of subjects and were probably/definitely related in 9% to antithrombotic therapy intensity. Most neurologic events occurred between 4 and 30 days postimplantation and sporadically thereafter. Pump change occurred in 56% of subjects. Use of an antithrombotic protocol for enrolled subjects was possible in this multicenter study. Incidence of significant bleeding and thromboembolic events was acceptable when balanced against life-saving benefits of VADs. Further studies are needed to optimize the antithrombotic management of this patient population. PMID- 27556153 TI - Active Clearance of Chest Tubes Reduces Re-Exploration for Bleeding After Ventricular Assist Device Implantation. AB - Chest tubes are utilized to evacuate shed blood after left ventricular assist device (LVAD) implantation, however, they can become clogged, leading to retained blood. We implemented a protocol for active tube clearance (ATC) of chest tubes to determine if this might reduce interventions for retained blood. A total of 252 patients underwent LVAD implantation. Seventy-seven patients had conventional chest tube drainage (group 1), whereas 175 patients had ATC (group 2). A univariate and multivariate analysis adjusting for the use of conventional sternotomy (CS) and minimally invasive left thoracotomy (MILT) was performed. Univariate analysis revealed a 65% reduction in re-exploration (43-15%, p < 0.001), and an 82% reduction in delayed sternal closure (DSC; 34-6%, p <0.001). In a sub-analysis of CS only, there continued to be statistically significant 53% reduction in re-exploration (45% vs. 21%, p = 0.0011), and a 77% reduction in DSC (35% vs. 8%, p < 0.001) in group 2. Using a logistic regression model adjusting for CS versus MILT, there was a significant reduction in re-exploration (odds ratio [OR] = 0.44 [confidence interval {CI} = 0.23-0.85], p = 0.014) and DSC (OR = 0.20 [CI = 0.08-0.46], p <0.001) in group 2. Actively maintaining chest tube patency after LVAD implantation significantly reduces re-exploration and DSC. PMID- 27556154 TI - Learning an EMG Controlled Game: Task-Specific Adaptations and Transfer. AB - Video games that aim to improve myoelectric control (myogames) are gaining popularity and are often part of the rehabilitation process following an upper limb amputation. However, direct evidence for their effect on prosthetic skill is limited. This study aimed to determine whether and how myogaming improves EMG control and whether performance improvements transfer to a prosthesis-simulator task. Able-bodied right-handed participants (N = 28) were randomly assigned to 1 of 2 groups. The intervention group was trained to control a video game (Breakout EMG) using the myosignals of wrist flexors and extensors. Controls played a regular Mario computer game. Both groups trained 20 minutes a day for 4 consecutive days. Before and after training, two tests were conducted: one level of the Breakout-EMG game, and grasping objects with a prosthesis-simulator. Results showed a larger increase of in-game accuracy for the Breakout-EMG group than for controls. The Breakout-EMG group moreover showed increased adaptation of the EMG signal to the game. No differences were found in using a prosthesis simulator. This study demonstrated that myogames lead to task-specific myocontrol skills. Transfer to a prosthesis task is therefore far from easy. We discuss several implications for future myogame designs. PMID- 27556155 TI - Clinical Significance of Serum Soluble CD Molecules to Assess Disease Activity in Vitiligo. AB - Importance: It is difficult to determine disease activity in vitiligo owing to the absence of inflammatory signs, such as erythema or scaling. A biomarker that could confirm active disease and indicate likely future disease progression would therefore be of considerable value. Objective: To investigate whether soluble CD27 (sCD27), sCD25, or sCD40L could be valuable biomarkers to determine disease activity in vitiligo and indicate likely future progression. Design, Setting, and Participants: A combined cross-sectional and prospective study was conducted at the department of dermatology at Ghent University Hospital between February 24, 2012, and December 12, 2015. Ninety-three patients with vitiligo were enrolled, including 83 individuals with nonsegmental vitiligo and 10 with segmental vitiligo. Blood sampling was performed, and sCD25, sCD27, and sCD40L were measured in serum. Main Outcomes and Measures: The associations between sCD levels, disease activity, and future progression were investigated. Results: Of the 93 patients included in the study, 51 were women (55%); median (interquartile range) age was 36.5 (26.0-49.8) years. Both sCD27 (21.5 ng/mL [16.1-30.0 ng/mL] vs 18.4 ng/mL [12.5-22.1 ng/mL]; P = .006) and sCD25 (2.6 ng/mL [2.1-3.4 ng/mL] vs 2.2 ng/mL [1.7-2.4 ng/mL]; P = .002) levels were associated with active disease. Moreover, a statistically significant link with disease progression after 3 to 6 months was found for sCD27 (21.7 [17.0-29.1] vs 16.6 [13.5-23.7]; P = .02) but not for sCD25 (2.8 ng/mL [2.2-3.4 ng/mL] vs 2.3 [1.9-2.8 ng/mL]; P = .053). Further in vitro experiments showed a correlation between sCD25 and interferon gamma (r = 0.562, P = .005), interleukin 10 (r = 0.453, P = .03), and sCD27 secretion (r = 0.549, P = .007). No associations were found for sCD40L levels. Conclusions and Relevance: This study demonstrates increased levels of sCD27 and sCD25 in patients with active vitiligo. Moreover, these results provide the first evidence that these markers have a capacity to indicate the probability of future disease progression, which supports their role as biomarkers in vitiligo. PMID- 27556157 TI - Integrative analysis of somatic mutations and transcriptomic data to functionally stratify breast cancer patients. AB - BACKGROUND: Somatic mutations can be used as potential biomarkers for subtyping and predicting outcomes for cancer patients. However, cancer patients often carry many somatic mutations, which do not always concentrate on specific genomic loci, suggesting that the mutations may affect common pathways or gene interaction networks instead of common genes. The challenge is thus to identify the functional relationships among the mutations using multi-modal data. We developed a novel approach for integrating patient somatic mutation, transcriptome and clinical data to mine underlying functional gene groups that can be used to stratify cancer patients into groups with different clinical outcomes. Specifically, we use distance correlation metric to mine the correlations between expression profiles of mutated genes from different patients. RESULTS: With this approach, we were able to cluster patients based on the functional relationships between the affected genes using their expression profiles, and to visualize the results using multi-dimensional scaling. Interestingly, we identified a stable subgroup of breast cancer patients that are highly enriched with ER-negative and triple-negative subtypes, and the somatic mutation genes they harbor were capable of acting as potential biomarkers to predict patient survival in several different breast cancer datasets, especially in ER-negative cohorts which has lacked reliable biomarkers. CONCLUSIONS: Our method provides a novel and promising approach for integrating genotyping and gene expression data in patient stratification in complex diseases. PMID- 27556156 TI - p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. AB - E-cadherin-mediated cell-cell adhesion is critical for naive pluripotency of cultured mouse embryonic stem cells (mESCs). E-cadherin-depleted mESC fail to downregulate their pluripotency program and are unable to initiate lineage commitment. To further explore the roles of cell adhesion molecules during mESC differentiation, we focused on p120 catenin (p120ctn). Although one key function of p120ctn is to stabilize and regulate cadherin-mediated cell-cell adhesion, it has many additional functions, including regulation of transcription and Rho GTPase activity. Here, we investigated the role of mouse p120ctn in early embryogenesis, mESC pluripotency and early fate determination. In contrast to the E-cadherin-null phenotype, p120ctn-null mESCs remained pluripotent, but their in vitro differentiation was incomplete. In particular, they failed to form cystic embryoid bodies and showed defects in primitive endoderm formation. To pinpoint the underlying mechanism, we undertook a structure-function approach. Rescue of p120ctn-null mESCs with different p120ctn wild-type and mutant expression constructs revealed that the long N-terminal domain of p120ctn and its regulatory domain for RhoA were dispensable, whereas its armadillo domain and interaction with E-cadherin were crucial for primitive endoderm formation. We conclude that p120ctn is not only an adaptor and regulator of E-cadherin, but is also indispensable for proper lineage commitment. PMID- 27556158 TI - Comprehensive comparison of molecular portraits between cell lines and tumors in breast cancer. AB - BACKGROUND: Proper cell models for breast cancer primary tumors have long been the focal point in the cancer's research. The genomic comparison between cell lines and tumors can investigate the similarity and dissimilarity and help to select right cell model to mimic tumor tissues to properly evaluate the drug reaction in vitro. In this paper, a comprehensive comparison in copy number variation (CNV), mutation, mRNA expression and protein expression between 68 breast cancer cell lines and 1375 primary breast tumors is conducted and presented. RESULTS: Using whole genome expression arrays, strong correlations were observed between cells and tumors. PAM50 gene expression differentiated them into four major breast cancer subtypes: Luminal A and B, HER2amp, and Basal-like in both cells and tumors partially. Genomic CNVs patterns were observed between tumors and cells across chromosomes in general. High C > T and C > G trans version rates were observed in both cells and tumors, while the cells had slightly higher somatic mutation rates than tumors. Clustering analysis on protein expression data can reasonably recover the breast cancer subtypes in cell lines and tumors. Although the drug-targeted proteins ER/PR and interesting mTOR/GSK3/TS2/PDK1/ER_P118 cluster had shown the consistent patterns between cells and tumor, low protein-based correlations were observed between cells and tumors. The expression consistency of mRNA verse protein between cell line and tumors reaches 0.7076. These important drug targets in breast cancer, ESR1, PGR, HER2, EGFR and AR have a high similarity in mRNA and protein variation in both tumors and cell lines. GATA3 and RP56KB1 are two promising drug targets for breast cancer. A total score developed from the four correlations among four molecular profiles suggests that cell lines, BT483, T47D and MDAMB453 have the highest similarity with tumors. CONCLUSIONS: The integrated data from across these multiple platforms demonstrates the existence of the similarity and dissimilarity of molecular features between breast cancer tumors and cell lines. The cell lines only mirror some but not all of the molecular properties of primary tumors. The study results add more evidence in selecting cell line models for breast cancer research. PMID- 27556162 TI - Cultural humility: The key to patient/family partnerships for making difficult decisions. PMID- 27556159 TI - Structure-guided selection of specificity determining positions in the human Kinome. AB - BACKGROUND: The human kinome contains many important drug targets. It is well known that inhibitors of protein kinases bind with very different selectivity profiles. This is also the case for inhibitors of many other protein families. The increased availability of protein 3D structures has provided much information on the structural variation within a given protein family. However, the relationship between structural variations and binding specificity is complex and incompletely understood. We have developed a structural bioinformatics approach which provides an analysis of key determinants of binding selectivity as a tool to enhance the rational design of drugs with a specific selectivity profile. RESULTS: We propose a greedy algorithm that computes a subset of residue positions in a multiple sequence alignment such that structural and chemical variation in those positions helps explain known binding affinities. By providing this information, the main purpose of the algorithm is to provide experimentalists with possible insights into how the selectivity profile of certain inhibitors is achieved, which is useful for lead optimization. In addition, the algorithm can also be used to predict binding affinities for structures whose affinity for a given inhibitor is unknown. The algorithm's performance is demonstrated using an extensive dataset for the human kinome. CONCLUSION: We show that the binding affinity of 38 different kinase inhibitors can be explained with consistently high precision and accuracy using the variation of at most six residue positions in the kinome binding site. We show for several inhibitors that we are able to identify residues that are known to be functionally important. PMID- 27556163 TI - A transformative service learning experience in Guatemala. PMID- 27556166 TI - New Drugs 2016, part 3. PMID- 27556167 TI - Understanding spinal cord compression. PMID- 27556165 TI - Lead poisoning: When an entire community is exposed. PMID- 27556168 TI - Finding time for Rose. PMID- 27556169 TI - Preventing perioperative hypothermia. PMID- 27556170 TI - Behavioral health: A natural nursing fit. PMID- 27556172 TI - Online resources about vaccination. PMID- 27556171 TI - Shigellosis. PMID- 27556173 TI - The little things. PMID- 27556175 TI - Cooperation Is Not Enough-Exploring Social-Ecological Micro-Foundations for Sustainable Common-Pool Resource Use [corrected]. AB - Cooperation amongst resource users holds the key to overcoming the social dilemma that characterizes community-based common-pool resource management. But is cooperation alone enough to achieve sustainable resource use? The short answer is no. Developing management strategies in a complex social-ecological environment also requires ecological knowledge and approaches to deal with perceived environmental uncertainty. Recent behavioral experimental research indicates variation in the degree to which a group of users can identify a sustainable exploitation level. In this paper, we identify social-ecological micro foundations that facilitate cooperative sustainable common-pool resource use. We do so by using an agent-based model (ABM) that is informed by behavioral common pool resource experiments. In these experiments, groups that cooperate do not necessarily manage the resource sustainably, but also over- or underexploit. By reproducing the patterns of the behavioral experiments in a qualitative way, the ABM represents a social-ecological explanation for the experimental observations. We find that the ecological knowledge of each group member cannot sufficiently explain the relationship between cooperation and sustainable resource use. Instead, the development of a sustainable exploitation level depends on the distribution of ecological knowledge among the group members, their influence on each other's knowledge, and the environmental uncertainty the individuals perceive. The study provides insights about critical social-ecological micro foundations underpinning collective action and sustainable resource management. These insights may inform policy-making, but also point to future research needs regarding the mechanisms of social learning, the development of shared management strategies and the interplay of social and ecological uncertainty. PMID- 27556176 TI - Meta-analysis of Vitamin D Deficiency and Risk of Atrial Fibrillation. AB - BACKGROUND: There are accumulating studies investigating the association between vitamin D status and the risk of atrial fibrillation (AF). However, the results in these studies were inconsistent in regard to the role of vitamin D deficiency in predicting the development of AF. HYPOTHESIS: Vitamin D deficiency is associated increased risk of AF. METHODS: Using PubMed and Embase databases, we searched for records published before March 2016. Additionally, a manual search was conducted using all review articles on this topic. Of the 587 initially identified records, 8 studies with a total of 27 307 patients were finally analyzed. RESULTS: In the categorical variable analysis, vitamin D deficiency was associated with the occurrence of AF (odds ratio: 1.31, 95% confidence interval: 1.06-1.62, P = 0.01). In the continuous variable analysis, higher vitamin D levels appear to protect against the development of AF (odds ratio: 0.92, 95% confidence interval: 0.87-0.97, P = 0.002). However, the association is weak on the pooled analysis of prospective cohort studies focused on new-onset AF (P = 0.07 and 0.04), whereas the pooled analysis of case-control studies mainly assessing for chronic AF strongly support such an association (both P < 0.0001). CONCLUSIONS: Vitamin D deficiency modestly increases the risk of AF. Further studies are needed to determine the if there is a direct causal relationship between vitamin D levels and AF and whether vitamin D supplements will prevent new-onset AF. PMID- 27556177 TI - Inside or Outside of the Heart? PMID- 27556178 TI - Phase II organ-preservation trial: Concurrent cisplatin and radiotherapy for advanced laryngeal cancer after response to docetaxel, cisplatin, and 5 fluorouracil-based induction chemotherapy. AB - BACKGROUND: The optimal treatment for locally advanced laryngeal cancer remains controversial. The purpose of this trial was to determine if the response to induction chemotherapy could select patients for organ preservation protocols, and improve larynx-preservation rates without compromising overall survival (OS). METHODS: The cohort comprised 12 patients with T3 disease and 14 with T4. Induction chemotherapy consisted of docetaxel, cisplatin, and 5-fluorouracil (TPF). Response to the first cycle was determined by examination and positron emission tomography (PET)-CT. Responders (>50% tumor reduction) underwent chemoradiation, whereas nonresponders underwent laryngectomy. RESULTS: Eighty three percent of the patients had a response and 17% had stable or progressive disease. At 2 years, the median OS was 80%, the larynx-preservation rate was 83%, and the disease-specific survival rate was 86%. Response to a single TPF cycle was associated with 2-year OS (92% vs 50%; p = .02). The T classification was not predictive of survival. CONCLUSION: Response to a single TPF-based cycle may identify patients with advanced laryngeal cancer who are amenable to organ preservation treatment. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 227-233, 2017. PMID- 27556179 TI - Yolk@Shell Nanoarchitectures with Bimetallic Nanocores-Synthesis and Electrocatalytic Applications. AB - In the present paper, we demonstrate a versatile approach for the one-pot synthesis of metal oxide yolk@shell nanostructures filled with bimetallic nanocores. This novel approach is based on the principles of hydrophobic nanoreactor soft-templating and is exemplified for the synthesis of various AgAuNP@tin-rich ITO (AgAu@ITOTR) yolk@shell nanomaterials. Hydrophobic nanoreactor soft-templating thereby takes advantage of polystyrene-block-poly(4 vinylpiridine) inverse micelles as two-compartment nanoreactor template, in which the core and the shell of the micelles serve as metal and metal oxide precursor reservoir, respectively. The composition, size and number of AuAg bimetallic nanoparticles incorporated within the ITOTR yolk@shell can easily be tuned. The conductivity of the ITOTR shell and the bimetallic composition of the AuAg nanoparticles, the as-synthesized AuAgNP@ITOTR yolk@shell materials could be used as efficient electrocatalysts for electrochemical glucose oxidation with improved onset potential when compared to their gold counterpart. PMID- 27556180 TI - Distinct role of interleukin-6 and tumor necrosis factor receptor-1 in oval cell- mediated liver regeneration and inflammation-associated hepatocarcinogenesis. AB - Interleukin 6 (IL6), tumor necrosis factor alpha (TNFalpha) and TNF receptor 1(TNFR1) have been shown to involve in oval cell proliferation and hepatocellular carcinoma (HCC) development. However, their role in these processes is still unclear. In the present study, by using hepatocytes-specific DDB1 deletion mouse models, we explored the role and mechanism of IL6, TNFalpha and TNFR1 in oval cell proliferation and HCC development in the context of inflammation, which is the common features of HCC pathogenesis in humans. Our results showed that IL6 promotes oval cell proliferation and liver regeneration, while TNFalpha/TNFR1 does not affect this process. Deletion of IL6 accelerates HCC development and increases tumor burden. The number of natural killer(NK) cells is significantly decreased in tumors without IL6, implying that IL6 suppresses HCC by NK cells. In contrast to IL6, TNFR1-mediated signaling pathway promotes HCC development, and deletion of TNFR1 reduced tumor incidence. Increased apoptosis, compensatory proliferation and activation of MAPK/MEK/ERK cascade contribute to the oncogenic function of TNFR1-mediated signaling pathway. Intriguingly, deletion of TNFalpha accelerates tumor development, which shows divergent roles of TNFalpha and TNFR1 in hepatocarcinogenesis. PMID- 27556181 TI - Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 target. AB - The p53 tumor suppressor inhibits cell growth through the activation of both cell cycle arrest and apoptosis, which maintain genome stability and prevent cancer development. Here, we report that intercellular adhesion molecule-2 (ICAM2) is transcriptionally activated by p53. Specifically, ICAM2 is induced by the p53 family and DNA damage in a p53-dependent manner. We identified a p53 binding sequence located within the ICAM2 gene that is responsive to wild-type p53, TAp73, and TAp63. In terms of function, we found that the ectopic expression of ICAM2 inhibited cancer cell migration and invasion. In addition, we demonstrated that silencing endogenous ICAM2 in cancer cells caused a marked increase in extracellular signal-regulated kinase (ERK) phosphorylation levels, suggesting that ICAM2 inhibits migration and invasion of cancer cells by suppressing ERK signaling. Moreover, ICAM2 is underexpressed in human cancer tissues containing mutant p53 as compared to those with wild-type p53. Notably, the decreased expression of ICAM2 is associated with poor survival in patients with various cancers. Our findings demonstrate that ICAM2 induction by p53 has a key role in inhibiting migration and invasion. PMID- 27556182 TI - Dux4 controls migration of mesenchymal stem cells through the Cxcr4-Sdf1 axis. AB - We performed transcriptome profiling of human immortalized myoblasts (MB) transiently expressing double homeobox transcription factor 4 (DUX4) and double homeobox transcription factor 4 centromeric (DUX4c) and identified 114 and 70 genes differentially expressed in DUX4- and DUX4c-transfected myoblasts, respectively. A significant number of differentially expressed genes were involved in inflammation, cellular migration and chemotaxis suggesting a role for DUX4 and DUX4c in these processes. DUX4 but not DUX4c overexpression resulted in upregulation of the CXCR4 (C-X-C motif Receptor 4) and CXCL12 (C-X-C motif ligand 12 also known as SDF1) expression in human immortalized myoblasts. In a Transwell cell migration assay, human bone marrow-derived mesenchymal stem cells (BMSCs) were migrating more efficiently towards human immortalized myoblasts overexpressing DUX4 as compared to controls; the migration efficiency of DUX4 transfected BMSCs was also increased. DUX4c overexpression in myoblasts or in BMSCs had no impact on the rate of BMSC migration. Antibodies against SDF1 and CXCR4 blocked the positive effect of DUX4 overexpression on BMSC migration. We propose that DUX4 controls the cellular migration of mesenchymal stem cells through the CXCR4 receptor. PMID- 27556183 TI - Ets2 knockdown inhibits tumorigenesis in esophageal squamous cell carcinoma in vivo and in vitro. AB - Increased expression of Ets2 is reported upregulated in esophageal squamous cell carcinoma tissue. However, the function of Ets2 in carcinogenesis of ESCC is poorly understood. Here, the rise of Ets2 was confirmed in ESCC cells and Ets2 depletion by RNA interference promotes cell apoptosis, inhibits cell proliferation, attenuates cell invasion and induces cell cycle G0/G1 arrest in vitro. Moreover, in vivo, Xenograft mouse model studies showed Ets2 knockdown inhibits tumor formation and metastasis significantly. Furthermore, Ets2 depletion inactivates the mTOR/p70S6K signaling pathway both in vitro and in vivo. Taken together, these findings strongly suggest that a critical role of Ets2 in human ESCC pathogenesis via the inactivation of the mTOR/p70S6K signaling pathway. PMID- 27556184 TI - Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis. AB - Treatment with alternating electric fields at an intermediate frequency (100-300 kHz), referred to as tumor treating fields (TTF) therapy, inhibits cancer cell proliferation. In the present study, we demonstrated that TTF application suppressed the metastatic potential of U87 and U373 glioblastoma cell lines via the NF-kB, MAPK and PI3K/AKT signaling pathways. Wound-healing and transwell assays showed that TTF suppressed cell migration and invasion compared with controls. Soft agar and three-dimensional culture assays showed that TTF inhibited both anchorage-dependent (cell proliferation) and anchorage-independent (colony formation) GBM cell growth. TTF dysregulated epithelial-to-mesenchymal transition-related genes, such as vimentin and E-cadherin, which partially accounted for TTF inhibition of cell migration and invasion. We further demonstrated that TTF application suppressed angiogenesis by downregulating VEGF, HIF1alpha and matrix metalloproteinases 2 and 9. TTF also inhibited NF-kB transcriptional activity. Collectively, our findings show that TTF represents a promising novel anti-invasion and anti-angiogenesis therapeutic strategy for use in GBM patients. PMID- 27556185 TI - PinX1: structure, regulation and its functions in cancer. AB - PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene located at human chromosome 8p23, playing a vital role in maintaining telomeres length and chromosome stability. It has been demonstrated to be involved in tumor genesis and progression in most malignancies. However, some researches showed opposing molecular status of PinX1 gene and its expression patterns in several other types of tumors. The pathogenic mechanism of PinX1 expression in human malignancy is not yet clear. Moreover, emerging evidence suggest that PinX1 (especially its TID domain) might be a potential new target cancer treatment. Therefore, PinX1 may be a new potential diagnostic biomarker and therapeutic target for human cancers, and may play different roles in different human cancers. The functions and the mechanisms of PinX1 in various human cancers remain unclear, suggesting the necessity of further extensive works of its role in tumor genesis and progression. PMID- 27556188 TI - CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma. AB - Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma. PMID- 27556187 TI - p53, a potential predictor of Helicobacter pylori infection-associated gastric carcinogenesis? AB - Helicobacter pylori (H. pylori) is an ancient and persistent inhabitant of the human stomach that is closely linked to the development of gastric cancer (GC). . Emerging evidence suggests that H. pylori strain interactions with gastric epithelial cells subvert the best- characterized p53 tumour suppressor pathway. A high prevalence of p53 mutations is related to H. pylori infection. H. pylori also accelerates p53 protein degradation by disturbing the MDM2-P53 feedback loop. Additionally, H. pylori triggers the alteration of other p53 isoforms. Dysregulation of p53 by H. pylori infection contributes to gastric carcinogenesis by mediating cell proliferation and apoptosis. This review focuses on the regulation of p53 in H. pylori infection-associated GC. PMID- 27556186 TI - Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. AB - EGFR is an extensively studied biomarker in head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the prognostic and predictive role of EGFR in HNSCC, focusing on the different molecular alterations in specific treatment modalities such as radiotherapy alone (RT), combination of surgery, RT and chemotherapy (CT), EGFR inhibitors. We considered EGFR at different molecular levels: protein expression, protein activation, gene copy number, polymorphisms, mutation, EGFRvIII expression and EGFR ligand expression.Considering RT alone, evidence supports the predictive and prognostic role of high EGFR expression only when evaluated by quantitative assays: this may help select the patients who can mostly benefit from accelerated treatment. Conversely, no predictive biomarkers are available when treatment is a combination of surgery, CT and RT. For this combined treatment, several studies indicate that EGFR expression represents a good prognostic parameter only when measured by a "quantitative" or at least semi quantitative method. With respect to EGFR inhibitors, neither EGFR expression nor increased gene copy number represent prognostic/predictive factors.If validated, nuclear EGFR, TGFalpha levels, EGFR phopshorylation and polymorphisms could represent additional prognostic factors in relation to combination of surgery, CT and RT, while EGFR polymorphisms and high amphiregulin levels could have prognostic value in patients treated with EGFR inhibitors. PMID- 27556189 TI - Application of PET/CT in treatment response evaluation and recurrence prediction in patients with newly-diagnosed multiple myeloma. AB - : Multiple myeloma (MM) causes osteolytic lesions which can be detected by 18F fluorodeoxyglucose positron emission tomography/Computed tomography (18F-FDG PET/CT). We prospectively involve 96 Newly diagnosed MM to take PET/CT scan at scheduled treatment time (figure 1), and 18F-FDG uptake of lesion was measured by SUVmax and T/Mmax. All MM patients took bortezomib based chemotherapy as induction and received ASCT and maintenance. All clinical features were analyzed with the PET/CT image changes, and some relationships between treatment response and FDG uptakes changes were found: Osteolytic lesions of MM uptakes higher FDG than healthy volunteers, and this trend is more obvious in extramedullary lesions. Compared to X-ray, PET/CT was more sensitive both in discoering bone as well as extramedullary lesions. In newly diagnosed MM, several adverse clinical factors were related to high FDG uptakes of bone lesions. Bone lesion FDG uptakes of MM with P53 mutation or with hypodiploidy and complex karyotype were also higher than those without such changes. In treatment response, PET/CT showed higher sensitivity in detecting tumor residual disease than immunofixation electrophoresis. But in relapse prediction, it might show false positive disease recurrences and the imaging changes might be influenced by infections and hemoglobulin levels. CONCLUSION: PET/CT is sensitive in discovering meduallary and extrameduallary lesions of MM, and the 18F-FDG uptake of lesions are related with clinical indictors and biological features of plasma cells. In evaluating treatment response and survival, PET/CT showed its superiority. But in predicting relapse or refractory, it may show false positive results. PMID- 27556191 TI - Role of Ultrasound in Complications of Hematopoetic Stem Cell Transplantation. AB - Hematopoetic stem cell transplantation (HSCT) is an established therapeutic option for both malignant and nonmalignant indications, whose incidence has continued to increase in recent years. Because of its lower cost and lack of radiation exposure, ultrasound examination is often the first-line imaging modality in evaluating patients both before and after HSCT. It is important for radiologists to be aware of sonographic manifestations of the complications that may arise from HSCT. In this study, we will review the basics of HSCT, the role of imaging, and ultrasound examination findings in common and uncommon complications arising from HSCT. PMID- 27556190 TI - Is Greater Frequency of Physical Activity Associated with Lower Prevalence of Depression in Older Community Residents? A Study From Brazil. PMID- 27556192 TI - Sonographic Features of Nodular Hashimoto Thyroiditis. AB - OBJECTIVE: The aim of the study was to analyze the sonographic features of nodular Hashimoto thyroiditis (HT) in patients with diffuse background thyroiditis and normal background thyroid parenchyma. SUBJECTS AND METHODS: Eighty-six patients who had fine-needle aspiration biopsy of 100 thyroid nodules confirmed to be HT and a thyroid ultrasound within 1 year of the biopsy were included in the study. Retrospective analysis of several sonographic features of each nodule was then performed. RESULTS: The mean age of patients with nodular HT was 53 years, 84% of which were female. Nodular HT occurred in a background of diffuse thyroiditis in 85% and in a homogeneous normal background in 15%. Ninety three percent of nodules were completely solid and 7% of nodules were cystic and solid. Although the sonographic appearance of nodular HT was variable, the most common appearance was a solid (93/100) and hypoechoic nodule (44/100) with a thin hypoechoic halo (42/100) without calcifications (96/100). On color Doppler, 17% of nodules showed peripheral hypervascularity, 14% of nodules were diffusely hypervascular, 34% were iso vascular, 32% were hypovascular, and 3% were avascular. The sonographic appearance of nodular HT was not significantly different in patients with diffuse background thyroiditis compared with those without background thyroiditis. CONCLUSIONS: The sonographic appearance of nodular HT is variable, but the most common appearance is a solid sharply circumscribed hypoechoic nodule with thin hypoechoic halo without calcification. There was no significant difference in the appearance of nodular HT in patients with diffuse background thyroiditis compared with patients with normal background thyroid parenchyma. PMID- 27556193 TI - The Lung Point Sign, not Pathognomonic of a Pneumothorax. AB - Since the development of portable ultrasonography equipment, this technology has provided clinicians the ability to evaluate a variety of lung pathology at the bedside, but we are still learning how to accurately interpret the acquired images. Adequate interpretation and recognition of certain signs is crucial to diagnosing pathological processes. In addition, such signs must be adequately correlated with the patient's medical condition. For instance, the "lung point sign" has been traditionally considered to be pathognomonic for the presence of a pneumothorax, yet such finding may be present in patients with bullous lung disease without a pneumothorax.We present a case of an 83-year-old man with underlying chronic obstructive pulmonary disease. Bedside ultrasonography identified a "lung point sign" initially suggesting a possible pneumothorax. Further evaluation demonstrated absence of pneumothorax, with the patient having a large bulla.To our knowledge, this is the first case reported demonstrating that the "lung point sign" is not always indicative of a pneumothorax. We discuss the importance of both clinical correlation and understanding of the underlying pathophysiology when reviewing ultrasound images to accurately interpret ultrasound findings. PMID- 27556194 TI - Sonographic Findings of Hydropneumothorax. AB - Ultrasound is increasingly being used in examination of the thorax. The sonographic features of normal aerated lung, abnormal lung, pneumothorax, and intrapleural fluid have been published. The sonographic features of uncommon intrathoracic syndromes are less known. Hydropneumothorax is an uncommon process in which the thoracic cavity contains both intrapleural air and water. Few published examples of the sonographic findings in hydropneumothorax exist. We present 3 illustrative cases of the sonographic features of hydropneumothorax with comparative imaging and a literature review of the topic. PMID- 27556195 TI - Acute Epididymo-orchitis-Related Global Testicular Infarction: Clinical and Ultrasound Findings With an Emphasis on the Juxta-epididymal String-of-Bead Sign. AB - Acute epididymo-orchitis (AEO)-related global testicular infarction (GTI) is rare. We report herein the clinical and ultrasound findings of 6 patients with AEO-related GTI. Seventeen patients with torsion-related GTI were also reviewed and compared. The echotexture of AEO-related GTI ranged from mildly inhomogeneous to diffuse heteroechoic, depending on the severity of testicular necrotic changes. All of the patients showed a juxta-epididymal string-of-bead pattern on color Doppler ultrasound, which was ascribed to patent arteries (5/6, 87%) and collateral vessels (1/6, 13%) in the tunica albuginea. There were no significant differences in age, laterality, leukocyte count, testicular volume ratio (infarcted/normal), frequencies of heteroechoic testicular parenchyma, scrotal skin thickening, and hydrocele between the 2 groups. However, the left testis was predominantly affected in both groups. Compared with torsion-related GTI, patients with AEO-related GTI had significantly longer duration from scrotal pain onset to surgery (13.5 +/- 5.2 vs 2.6 +/- 2.0 days, P < 0.001), a higher level of serum C-reactive protein (110.0 +/- 82.0 vs 41.2 +/- 35.9 mg/dL, P = 0.013), a higher frequency of the juxta-epididymal string-of-bead sign (100% vs 12%, P < 0.001), and a lower frequency of the whirlpool/knot sign (0% vs 88%, P = 0.002). Although the testis in AEO-related GTI may appear variable from mildly to extensively heteroechoic on gray-scale ultrasound, this unusual disease can be characterized by an avascular testis with a juxta-epididymal string-of-bead sign on color Doppler ultrasound. PMID- 27556196 TI - Xanthogranulomatous Pyelonephritis. PMID- 27556197 TI - Acromioclavicular Joint Cyst. PMID- 27556199 TI - Seven great achievements in pediatric research in the past 40 y. PMID- 27556200 TI - The impact of clinical use on the torsional behavior of Reciproc and WaveOne instruments. AB - OBJECTIVE: The aim of this study was to assess the influence of clinical use, in vivo, on the torsional behavior of Reciproc and WaveOne instruments considering the possibility that they degraded with use. MATERIAL AND METHODS: Diameter at each millimeter, pitch length, and area at 3 mm from the tip were determined for both types of instruments. Twenty-four instruments, size 25, 0.08 taper, of each system were divided into two groups (n=12 each): Control Group (CG), in which new Reciproc (RC) and WaveOne Primary (WO) instruments were tested in torsion until rupture based on ISO 3630-1; and Experimental Group (EG), in which each new instrument was clinically used to clean and shape the root canals of one molar. After clinical use, the instruments were analyzed using optical and scanning electron microscopy and subsequently tested in torsion until fracture. Data were analyzed using one-way analysis of variance at a=.05. RESULTS: WO instruments showed significantly higher mean values of cross-sectional area A3 (P=0.000) and smaller pitch lengths than RC instruments with no statistically significant differences in the diameter at D3 (P=0.521). No significant differences in torsional resistance between the RC and WO new instruments (P=0.134) were found. The clinical use resulted in a tendency of reduction in the maximum torque of the analyzed instruments but no statistically significant difference was observed between them (P=0.327). During the preparation of the root canals, two fractured RC instruments and longitudinal and transversal cracks in RC and WO instruments were observed through SEM analysis. CONCLUSION: After clinical use, no statistically significant reduction in the torsional resistance was observed. PMID- 27556201 TI - Water interaction and bond strength to dentin of dye-labelled adhesive as a function of the addition of rhodamine B. AB - OBJECTIVE: This study investigated the effect of the fluorescent dye rhodamine B (RB) for interfacial micromorphology analysis of dental composite restorations on water sorption/solubility (WS/WSL) and microtensile bond strength to dentin (uTBS) of a 3-step total etch and a 2-step self-etch adhesive system. MATERIAL AND METHODS: The adhesives Adper Scotchbond Multi-Purpose (MP) and Clearfil SE Bond (SE) were mixed with 0.1 mg/mL of RB. For the WS/WSL tests, cured resin disks (5.0 mm in diameter x 0.8 mm thick) were prepared and assigned into four groups (n=10): MP, MP-RB, SE, and SE-RB. For uTBS assessment, extracted human third molars (n=40) had the flat occlusal dentin prepared and assigned into the same experimental groups (n=10). After the bonding and restoration procedures, specimens were sectioned in rectangular beams, stored in water and tested after seven days or after 12 months. The failure mode of fractured specimens was qualitatively evaluated under optical microscope (x40). Data from WS/WSL and uTBS were assessed by one-way and three-way ANOVA, respectively, and Tukey's test (alpha=5%). RESULTS: RB increased the WSL of MP and SE. On the other hand, WS of both MP and SE was not affected by the addition of RB. No significance in uTBS between MP and MP-RB for seven days or one year was observed, whereas for SE a decrease in the uTBS means occurred in both storage times. CONCLUSIONS: RB should be incorporated into non-simplified DBSs with caution, as it can interfere with their physical-mechanical properties, leading to a possible misinterpretation of bonded interface. PMID- 27556202 TI - Osseointegration aspects of placed implant in bone reconstruction with newly developed block-type interconnected porous calcium hydroxyapatite. AB - OBJECTIVES: The purpose of this study was to evaluate the osseointegration of dental implant in bone reconstructions with interconnected porous calcium hydroxyapatite (IP-CHA). MATERIAL AND METHODS: The IP-CHA cylinders (D; 4.3 mm, H; 10.0 mm) were placed into bone sockets in each side of the femurs of four male dogs. The IP-CHA on the right side was a 24-week sample. Twelve weeks after placement, a titanium implant was placed into a socket that was prepared in half of the placed IP-CHA cylinder on the right side. On the left side, another IP-CHA cylinder was placed as a 12-week sample. After another 12 weeks, the samples were harvested, and the bone regeneration and bone-implant contact (BIC) ratios were measured. RESULTS: New bone formation area was superior in the 24-week IP-CHA compared with the 12-week IP-CHA. BIC was not significantly different between IP CHA and the parent sites. Osseointegration was detected around the implant in IP CHA-reconstructed bone. CONCLUSION: Our preliminary results suggest that IP-CHA may be a suitable bone graft material for reconstructing bones that require implant placement. PMID- 27556203 TI - Effects of low-level laser therapy on stem cells from human exfoliated deciduous teeth. AB - OBJECTIVE: This study aimed to evaluate the influence of different laser therapy energy densities on SHED viability and proliferation. MATERIAL AND METHODS: SHED were irradiated according to the groups: I (1.2 J/cm2 - 0.5 mW - 10 s), II (2.5 J/cm2 - 10 mW - 10 s), III (3.7 J/cm2 - 15 mW - 10 s), IV (5.0 J/cm2 - 20 mW - 10 s), V (6.2 J/cm2 - 25 mW - 10 s), and VI (not irradiated - control group). Cell viability was assessed 6 and 24 h after irradiation measuring the mitochondrial activity and using the Crystal Violet assay. Cell proliferation was assessed after 24, 48, and 72 h of irradiation by SRB assay. RESULTS: MTT assay demonstrated differences from 6 to 24 hours after irradiation. After 24 h, groups I and IV showed higher absorbance values than those of control group. Crystal Violet assay showed statistically differences in the absorbance rate from 6 to 24 h after irradiation for groups III and VI. At 24 h after irradiation, Group III absorbance rate was greater than that of groups I, II, and IV. Group VI absorbance rate was greater than that of groups I and IV. SRB assay showed that the group I had higher rates than those of groups II, III, V, and VI, at 24 h after irradiation. After 48 h, group I exhibited the greatest cell proliferation rate followed by groups III, V, and VI. After 72 h, group III exhibited the lowest cell proliferation rate than those of groups II, IV, and V. CONCLUSIONS: The Low-Level Laser Therapy energy densities used in this study did not cause loss of cell viability and stimulated SHED proliferation within the parameters described in this study. PMID- 27556204 TI - Cytotoxicity and cytokine expression induced by silorane and methacrylate-based composite resins. AB - OBJECTIVE: The aim of this study was to evaluate cytotoxicity and cytokine production induced by light-cured or non-light-cured methacrylate-based and silorane composite resins in RAW 264.7 macrophages. MATERIAL AND METHODS: Cells were stimulated with the extracts from light-cured or non-light-cured composite resins. After incubation for 24 h, cytotoxicity was assessed with the lactate dehydrogenase (LDH) and methyl thiazolyl tetrazolium (MTT) assays, and total protein was quantified using the Lowry method. TNF-alpha detection was examined with an enzyme-linked immunosorbent assay (ELISA) conducted with cell supernatants after cell stimulation for 6, 12, and 24 h. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's post hoc test (alpha=0.05). RESULTS: KaloreTM and FiltekTM Silorane were cytotoxic with or without light curing (p<0.05) after 24 h of incubation. KaloreTM stimulated the early production of TNF-alpha in comparison with control (p<0.05), whereas FiltekTM Silorane did not affect TNF-alpha levels after 6 and 12 h (p>0.05). However, after 24 h FiltekTM Silorane inhibited the production of TNF-alpha (p<0.05). CONCLUSIONS: KaloreTM and FiltekTM Silorane were cytotoxic regardless of light curing. The extract obtained from KaloreTM after 15 days of incubation stimulated the production of TNF-alpha, unlike that obtained from FiltekTM Silorane. PMID- 27556205 TI - Characterisation and microleakage of a new hydrophilic fissure sealant - UltraSeal XT(r) hydroTM. AB - OBJECTIVES: The aim of this study was to characterise the new hydrophilic fissure sealant, UltraSeal XT(r) hydroTM (Ultradent Products, USA), and to investigate its in vitro resistance to microleakage after placement on conventionally acid etched and sequentially lased and acid etched molars. MATERIAL AND METHODS: The sealant was characterised by Fourier transform infra-red spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and Vickers indentation test. Occlusal surfaces of extracted human molars were either conventionally acid etched (n=10), or sequentially acid etched and laser irradiated (n=10). UltraSeal XT(r) hydroTM was applied to both groups of teeth which were then subjected to 2,500 thermocycles between 5 and 55 degrees C prior to microleakage assessment by fuchsin dye penetration. RESULTS: UltraSeal XT(r) hydroTM is an acrylate-based sealant that achieved a degree of conversion of 50.6+/-2.2% and a Vickers microhardness of 24.2+/-1.5 under standard light curing (1,000 mWcm-2 for 20 s). Fluoride ion release is negligible within a 14-day period. SEM and EDX analyses indicated that the sealant comprises irregular submicron and nano-sized silicon-, barium-, and aluminium-bearing filler phases embedded in a ductile matrix. Laser preconditioning was found to significantly reduce microleakage (Mann-Whitney U test, p<0.001). The lased teeth presented enhanced surface roughness on a 50 to 100 MUm scale that caused the segregation and concentration of the filler particles at the enamel-sealant interface. CONCLUSION: Laser preconditioning significantly decreased microleakage and increased enamel surface roughness, which caused zoning of the filler particles at the enamel-sealant interface. PMID- 27556206 TI - Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease. AB - MATERIAL AND METHODS: This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, and TNF-alpha were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. RESULTS: CAD patients that experienced major events had higher concentrations of IFN-gamma (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-alpha (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-gamma log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-alpha were associated with higher mean CA loss (R2=0.07). CONCLUSION: Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients. PMID- 27556207 TI - Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer. AB - OBJECTIVE: This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. MATERIAL AND METHODS: A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. RESULTS: From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). CONCLUSIONS: Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors. PMID- 27556208 TI - MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements. AB - OBJECTIVE: In this study, we evaluated the association between the MMP1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with MMP-1 mRNA levels in vivo. MATERIAL AND METHODS: MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, IL-17A, IL-21, IL-10, IL-4, IL-9, and FOXp3 were determined via RealTimePCR in DNA/RNA samples from patients presenting periapical granulomas (N=111, for both genotyping and expression analysis) and control subjects (N=214 for genotyping and N=26 for expression analysis). The Shapiro-Wilk, Fisher, Pearson, Chi-square ordinal least squares regression tests were used for data analysis (p<0.05 was considered statistically significant). RESULTS: The MMP1 1607 1G/2G and 1G/2G+2G/2G genotypes were significantly more prevalent in the patients than in controls, comprising a risk factor for periapical lesions development. MMP-1 mRNA levels were higher in periapical lesions than in healthy periodontal ligament samples, as well as higher in active than in inactive lesions. The polymorphic allele 2G carriers presented a significantly higher MMP 1 mRNA expression when compared with the 1G/1G genotype group. The ordered logistic regression demonstrated a significant correlation between the genetic polymorphism and the expression levels of MMP-1. Additionally, the pro- and anti inflammatory cytokines IL-17A, IFN-g, TNF-a, IL-21, IL-10, IL-9, and IL-4 were significant as complementary explanatory variables of MMP-1 expression. CONCLUSION: The MMP1-1607 SNP was identified as a risk factor for periapical lesions development, possibly due to its association with increased MMP-1 mRNA levels in periapical lesions. The MMP-1 expression is also under the control of the inflammatory milieu elements, being the cytokines TNF-a, IL-21, IL-17A, and IFN-g associated with increased MMP-1 levels in periapical lesions, while IL-10, IL-9, or IL-4 presented an inverse association. PMID- 27556209 TI - Aging impairs osteoblast differentiation of mesenchymal stem cells grown on titanium by favoring adipogenesis. AB - OBJECTIVE: We investigated the osteoblast and adipocyte differentiation of mesenchymal stem cells (MSCs) from young and aged rats cultured on Ti. MATERIAL AND METHODS: Bone marrow MSCs derived from 1-month and 21-month rats were cultured on Ti discs under osteogenic conditions for periods of up to 21 days and osteoblast and adipocyte markers were evaluated. RESULTS: Cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene expression of RUNX2, osterix, ALP, bone sialoprotein, osteopontin, and osteocalcin were reduced in cultures of 21-month rats compared with 1-month rats grown on Ti. Gene expression of PPAR-gamma , adipocyte protein 2, and resistin and lipid accumulation were increased in cultures of 21-month rats compared with 1-month rats grown on the same conditions. CONCLUSIONS: These results indicate that the lower osteogenic potential of MSCs derived from aged rats compared with young rats goes along with the higher adipogenic potential in cultures grown on Ti surface. This unbalance between osteoblast and adipocyte differentiation should be considered in dental implant therapy to the elderly population. PMID- 27556210 TI - Comparison of the marginal adaptation of direct and indirect composite inlay restorations with optical coherence tomography. AB - OBJECTIVE: The purpose of the study was to use the photonic imaging modality of optical coherence tomography (OCT) to compare the marginal adaptation of composite inlays fabricated by direct and indirect techniques. MATERIAL AND METHODS: Class II cavities were prepared on 34 extracted human molar teeth. The cavities were randomly divided into two groups according to the inlay fabrication technique. The first group was directly restored on cavities with a composite (Esthet X HD, Dentsply, Germany) after isolating. The second group was indirectly restored with the same composite material. Marginal adaptations were scanned before cementation with an invisible infrared light beam of OCT (Thorlabs), allowing measurement in 200 um intervals. Restorations were cemented with a self adhesive cement resin (SmartCem2, Dentsply), and then marginal adaptations were again measured with OCT. Mean values were statistically compared by using independent-samples t-test and paired samples t-test (p<0.05), before and after cementation. RESULTS: Direct inlays presented statistically smaller marginal discrepancy values than indirect inlays, before (p=0.00001442) and after (p=0.00001466) cementation. Marginal discrepancy values were increased for all restorations after cementation (p=0.00008839, p=0.000000952 for direct and indirect inlays, respectively). The mean marginal discrepancy value of the direct group increased from 56.88+/-20.04 um to 91.88+/-31.7 um, whereas the indirect group increased from 107.54+/-35.63 um to 170.29+/-54.83 um. Different techniques are available to detect marginal adaptation of restorations, but the OCT system can give quantitative information about resin cement thickness and its interaction between tooth and restoration in a nondestructive manner. CONCLUSIONS: Direct inlays presented smaller marginal discrepancy than indirect inlays. The marginal discrepancy values were increased for all restorations that refer to cement thickness after cementation. PMID- 27556211 TI - Influence of resin cement shade on the color and translucency of ceramic veneers. AB - OBJECTIVE: This in vitro study evaluated the effect of two different shades of resin cement (RC- A1 and A3) layer on color change, translucency parameter (TP), and chroma of low (LT) and high (HT) translucent reinforced lithium disilicate ceramic laminates. MATERIAL AND METHODS: One dual-cured RC (Variolink II, A1- and A3-shade, Ivoclar Vivadent) was applied to 1-mm thick ceramic discs to create thin RC films (100 um thick) under the ceramics. The RC was exposed to light from a LED curing unit. Color change (DeltaE) of ceramic discs was measured according to CIEL*a*b* system with a standard illuminant D65 in reflectance mode in a spectrophotometer, operating in the light range of 360-740 nm, equipped with an integrating sphere. The color difference between black (B) and white (W) background readings was used for TP analysis, while chroma was calculated by the formula C*ab=(a*2+b*2)1/2. DeltaE of 3.3 was set as the threshold of clinically unacceptable. The results were evaluated by two-way ANOVA followed by Tukey's post hoc test. RESULTS: HT ceramics showed higher DeltaE and higher TP than LT ceramics. A3-shade RC promoted higher DeltaE than A1-shade cement, regardless of the ceramic translucency. No significant difference in TP was noted between ceramic discs with A1- and those with A3-shade cement. Ceramic with underlying RC showed lower TP than discs without RC. HT ceramics showed lower chroma than LT ceramics, regardless of the resin cement shade. The presence of A3-shade RC resulted in higher chroma than the presence of A1-shade RC. CONCLUSIONS: Darker underlying RC layer promoted more pronounced changes in ceramic translucency, chroma, and shade of high translucent ceramic veneers. These differences may not be clinically differentiable. PMID- 27556212 TI - Higher prevalence and gene amplification of HPV16 in oropharynx as compared to oral cavity. AB - OBJECTIVE: The objective of this study was to clarify differences regarding HPV16 infection and gene amplification between the oral cavity and oropharynx in healthy individuals. MATERIAL AND METHODS: The subjects were 94 healthy asymptomatic individuals (41 males, 53 females; mean age 58.6 years, range 16-97 years) who visited the Department of Oral and Maxillofacial Reconstructive Surgery of the Hiroshima University Hospital from 2014 to 2015. Oral epithelial cells were collected from oral rinse and pharynx gargle samples and placed in saline. The human endogenous retrovirus gene ERV3-1 was used as a reference to estimate the number of human cells in each sample. DNA samples were extracted from approximately 10,000 human cells and tested for HPV16 DNA by PCR using a type-specific primer. Similarly, we analyzed the HPV16 viral copy number in HPV16 positive cases using real-time PCR to examine genomic amplification. RESULTS: The percentage of HPV16-positive cases was higher in the gargle (28.7%) as compared to the rinse (16.0%) samples. In the oral rinse samples, males (26.8%) showed a significantly higher rate of HPV16 than females (7.5%) (P=0.021). Importantly, in older subjects (aged 60-89 years), gargle samples showed a significantly higher rate of HPV16 (33.3%) than oral rinse samples (13.7%) (P=0.034). The average number of viral copies was approximately 8 times higher in the gargle than in the oral rinse samples (0.16+/-0.27 vs. 1.35+/-1.26 copy numbers per cell), a significant difference (P<0.001). CONCLUSION: Our findings suggest that the oropharynx is more susceptible to HPV16 infection as compared to the oral cavity, while HPV16 gene amplification is also more commonly found in the oropharynx. PMID- 27556213 TI - Effect of silver nanoparticles on the physicochemical and antimicrobial properties of an orthodontic adhesive. AB - OBJECTIVE: This study aimed to incorporate silver nanoparticle solutions (AgNP) in an orthodontic adhesive and evaluate its physicochemical and antimicrobial properties. MATERIAL AND METHODS: Silver nanoparticle solutions were added to a commercial adhesive in different concentrations (w/w): 0%, 0.11%, 0.18%, and 0.33%. Shear bond strength (SBS) test was performed after bonding metal brackets to enamel. Raman spectroscopy was used to analyze in situ the degree of conversion (DC) of the adhesive layer. The surface free energy (SFE) was evaluated after the measurement of contact angles. Growth inhibition of Streptococcus mutans in liquid and solid media was determined by colony-forming unit count and inhibition halo, respectively. One-way ANOVA was performed for SBS, DC, SFE, and growth inhibition. RESULTS: The incorporation of AgNP solution decreased the SBS (p<0.001) and DC in situ (p<0.001) values. SFE decreased after addition of 0.18% and 0.33% AgNP. Growth inhibition of S. mutans in liquid media was obtained after silver addition (p<0.05). CONCLUSIONS: The addition of AgNP solutions to TransbondTM XT adhesive primer inhibited S. mutans growth. SBS, DC, and SFE values decreased after incorporation up to 0.33% AgNP solution without compromising the chemical and physical properties of the adhesive. PMID- 27556214 TI - Occlusal changes secondary to temporomandibular joint conditions: a critical review and implications for clinical practice. AB - OBJECTIVES: The aim of this article is to present the most commonly occlusal changes secondary to TMD. METHODS: The clinical presentation of these conditions is discussed. Details regarding diagnosis, treatment, and follow-up of patients presenting TMD prior or during treatment are also presented. CONCLUSIONS: All plans for irreversible therapy should be preceded by a meticulous analysis of TMD signs and symptoms in such a way that patients are not submitted to irreversible treatment, based on an untrue occlusal relationship, secondary to articular and/or muscular disorders. When present, TMD symptoms must always be controlled to reestablish a "normal" occlusion and allow proper treatment strategy. PMID- 27556215 TI - Curcumin Protects Trabecular Meshwork Cells From Oxidative Stress. AB - PURPOSE: Glaucoma is closely linked with oxidative stress and inflammation, and difficult to treat. Its occurrence frequently is contributed by the failure of the trabecular meshwork (TM). Curcumin is known as an antioxidative and anti inflammatory substance, possessing the potential to treat glaucoma. METHODS: Using TM cells as the in vitro model system, we investigated the effects of curcumin on oxidative stress-induced markers for TM impairments, including cell death, production of intracellular reactive oxygen species (iROS), induction of proinflammatory proteins, activation of senescence marker, accumulation of carbonylated proteins, and apoptotic cell numbers. RESULTS: Curcumin treatment protected TM cells against oxidative stress-induced cell death. Curcumin treatment at concentrations between 1 and 20 MUM reduced the production of iROS in H2O2-exposed TM cells in a dose-dependent manner. Further studies demonstrated that curcumin treatment (20 MUM) significantly inhibited proinflammatory factors, including IL-6, ELAM-1, IL-1alpha, and IL-8, whereas it decreased activities of senescence marker SA-beta-gal, and lowered levels of carbonylated proteins and apoptotic cell numbers. CONCLUSIONS: Curcumin is capable of protecting TM cells against oxidative stress, shedding new light on potential treatment for glaucoma. PMID- 27556217 TI - Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma. AB - PURPOSE: We developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months. METHODS: The release rates of DE-117-loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE-117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS). RESULTS: In vitro release of DE-117 showed zero-order release with a release rate of 0.5 MUg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE-117 and hDE-117 (the hydrolyzed active form of DE-117) in ocular tissues (cornea, iris-ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE-117 and its conversion to hDE-117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE-117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device. CONCLUSIONS: Proof of-concept PCL drug delivery devices containing DE-117 show promise as a long term glaucoma treatment based on their zero-order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues. PMID- 27556218 TI - The Combination of PlGF Inhibition and MMC as a Novel Anti-Scarring Strategy for Glaucoma Filtration Surgery. AB - PURPOSE: The complementary effects of mitomycin-C (MMC) and anti-placental growth factor (PlGF) therapy were explored and compared to the combined administration of MMC and aflibercept. Additionally, the effect of PlGF (inhibition) on IOP was investigated, since aqueous PlGF is known to be upregulated in glaucoma patients. METHODS: In the trabeculectomy mouse model, intracameral injection(s) of the PlGF inhibitor (5D11D4) were compared to MMC or aflibercept and to the combination of both compounds. Treatment outcome was studied by bleb investigation and by Sirius Red staining. The effect of subconjunctival PlGF administration and topical 5D11D4 on IOP was investigated in normotensive mice and was compared to topical administration of latanoprost, the gold standard for IOP-lowering. RESULTS: Combination of MMC and 5D11D4 was able to significantly improve surgical outcome compared to monotherapy of MMC or 5D11D4 (n = 20; P < 0.001). Compared to combined treatment of MMC with aflibercept, the simultaneous administration of MMC and 5D11D4 was equally efficacious in improving surgical outcome (n = 15; P = 0.88). In normotensive mice, 5D11D4 was able to significantly reduce the IOP elevation induced by PlGF (n = 10; P < 0.05), whereas no effect of 5D11D4 was seen in naive mice, which was in contrast to latanoprost. CONCLUSIONS: The current data suggest that application of MMC together with PlGF inhibition may have complementary effects in the improvement of surgical outcome and is equally efficacious as the combined treatment of MMC and aflibercept. Inhibition of PlGF also might open alternative perspectives as IOP-lowering strategy for glaucoma patients with increased aqueous PlGF levels. PMID- 27556216 TI - Acute and Chronic Hyperglycemia Elicit JIP1/JNK-Mediated Endothelial Vasodilator Dysfunction of Retinal Arterioles. AB - PURPOSE: Hyperglycemia, a hallmark of diabetes mellitus, is associated with retinal inflammation and impairment of endothelium-dependent nitric oxide (NO) mediated dilation of retinal arterioles. However, molecular mechanisms involved in this diminished endothelial vasodilator function remain unclear. We examined whether inflammatory stress-activated kinases, c-Jun N-terminal kinase (JNK) and p38, contribute to retinal arteriolar dysfunction during exposure to acute and chronic hyperglycemia. METHODS: Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2 weeks; chronic hyperglycemia, 471 +/- 23 mg/dL) or age-matched control pigs (euglycemia, 79 +/- 5 mg/dL), and then cannulated and pressurized for vasoreactivity study. For acute hyperglycemia study, vessels from nondiabetic pigs were exposed intraluminally to high glucose (25 mM ~ 450 mg/dL) for 2 hours, and normal glucose (5 mM ~ 90 mg/dL) served as the control. RESULTS: Endothelium-dependent vasodilation to bradykinin was reduced in a similar manner after exposure to acute or chronic hyperglycemia. Administration of NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) nearly abolished vasodilations either in control (euglycemia and normal glucose) or hyperglycemic (acute and chronic) vessels. Treatment of either acute or chronic hyperglycemic vessels with JNK inhibitor SP600125 or JNK-interacting protein-1 (JIP1) inhibitor BI-78D3, but not p38 inhibitor SB203580, preserved bradykinin-induced dilation in an L-NAME-sensitive manner. By contrast, endothelium-independent vasodilation to sodium nitroprusside was unaffected by acute or chronic hyperglycemia. CONCLUSIONS: Activation of JIP1/JNK signaling in retinal arterioles during exposure to acute or chronic hyperglycemia leads to selective impairment of endothelium-dependent NO-mediated dilation. Therapeutic targeting of the vascular JNK pathway may improve retinal endothelial vasodilator function during early diabetes. PMID- 27556219 TI - Inhibitory effects of Zanthoxylum rhoifolium Lam. (Rutaceae) against the infection and infectivity of macrophages by Leishmania amazonensis. AB - Zanthoxylum rhoifolium Lam. (Rutaceae) has been traditionally used in the treatment of microbial infections and parasitic diseases. In the present study, the antileishmanial effect induced by the ethanol extract of stem barks from Z. rhoifolium (ZR-EEtOH) and its n-hexane fraction (ZR-FHEX) on infection and infectivity of murine macrophages by promastigote forms of Leishmania amazonensis were investigated. In different set of experiments, macrophages or promastigotes were pretreated with ZR-EEtOH or ZR-FHEX at non-lethal concentrations for 24 hours, and then macrophages were submitted to infection by promastigotes. Moreover, their effects on activation of macrophages, as well as on the DNA content, size and number of promastigotes by flow cytometry were also evaluated. The infection rate and the number of internalized amastigote forms were markedly decreased after pretreatment of macrophages or promastigotes when compared with non-treated cells. The increase in phagocytic capability and nitrite content was also observed. Furthermore, the decrease of DNA content, size and number of promastigotes was also observed. In conclusion, ZR-EEtOH and ZR-FHEX promoted a markedly significant antileishmanial effect and reduction of infection of macrophages, probably underlying defense mechanisms activation in macrophages. These findings reinforce the potential application of Z. rhoifolium in the treatment of leishmaniasis. PMID- 27556220 TI - Modeling the reflection of Photosynthetically active radiation in a monodominant floodable forest in the Pantanal of Mato Grosso State using multivariate statistics and neural networks. AB - The study of radiation entrance and exit dynamics and energy consumption in a system is important for understanding the environmental processes that rule the biosphere-atmosphere interactions of all ecosystems. This study provides an analysis of the interaction of energy in the form of photosynthetically active radiation (PAR) in the Pantanal, a Brazilian wetland forest, by studying the variation of PAR reflectance and its interaction with local rainfall. The study site is located in Private Reserve of Natural Heritage, Mato Grosso State, Brazil, where the vegetation is a monodominant forest of Vochysia divergens Phol. The results showed a high correlation between the reflection of visible radiation and rainfall; however, the behavior was not the same at the three heights studied. An analysis of the hourly variation of the reflected waves also showed the seasonality of these phenomena in relation to the dry and rainy seasons. A predictive model for PAR was developed with a neural network that has a hidden layer, and it showed a determination coefficient of 0.938. This model showed that the Julian day and time of measurements had an inverse association with the wind profile and a direct association with the relative humidity profile. PMID- 27556221 TI - Science communication in Brazil: A historical review and considerations about the current situation. AB - In this paper, we present a historical overview of the science communication activities in Brazil since the nineteenth century and we analyze the current situation and its main concerns. The principal scopes and tools for science communication discussed here are the following: science centers and museums, mass media and large public events for communicating science and technology (S&T). In recent years, such activities have had a significant breakthrough in Brazil. Yet, there is still a long way to go in order to deliver a quality and extensive science and technology communication to the Brazilians as well as to achieve a suitable level of social appropriation of knowledge on S&T by the Brazilian society. Some of the main challenges that we are facing are discussed herein. PMID- 27556222 TI - Scientific Performance of Brazilian Researchers in Pharmacology with grants from CNPq: A comparative study within the Brazilian categories. AB - In Brazil, scientific performance of researchers is one important criteria for decision-making in grant allocation. In this context, this study aimed to evaluate and compare the profile of 82 seniors' investigators (graded as level 1A D) which were receiving CNPq (National Council for Scientific and Technological Development) productivity grant in Pharmacology, by analyzing the pattern of citation of their papers and h-index. Total documents, citations (with and without self-citations) and h-index (with and without self-citations) were retrieved from the Scopus database. The results indicated a clear difference among researchers from the higher categories (1A and 1B) in most of the parameters analyzed. However, no noticeable differentiation was found between researchers from grant category 1C and 1D. The results presented here may inform the scientific community and the grant agencies on the profile of PQ 1(A-D) fellows of Pharmacology, and may help to define new differences within CNPq grant categories, and consequently, a better allocation of grants. PMID- 27556223 TI - Miconia gigantea, a long-forgotten endemic and endangered species of Melastomataceae in the Brazilian Atlantic Forest. AB - Taxonomic and floristic studies in the state of Rio de Janeiro allowed the rediscovery of Miconia gigantea, an endemic species to the Atlantic Forest, until recently known only from the type specimen, collected over 100 years by A.F.M. Glaziou. We present an amended and detailed description of M. gigantea, providing characteristics of the flowers, fruits and seeds, in addition to illustrations, comments about taxonomic affinities with closely related species, the presently known distribution together with new occurrence records, and the conservation status. PMID- 27556224 TI - Sloths of the Atlantic Forest in the sixteenth and seventeenth centuries. AB - Sloths were a curiosity item for Europeans in the 16th and 17th centuries, and several descriptions of them exist in bestiaries and texts of that time. Here, we assemble the descriptions and drawings of sloths from the travellers and naturalists of those centuries in the Brazilian Atlantic Forest. The sloth was a novelty to the European audience, and it was described in many strange and inaccurate ways: as a monster, a beast, or an odd child. It served as a source of admiration, amusement, and confusion among naturalists and travellers of the 16th and 17th centuries. We also raised the question about the identity of Carolus Clusius' sloth, a drawing published in Exoticorum libri decem (1605). We compared his drawing with earlier depictions and descriptions, from Andre Thevet (1516 1590) to George Marcgrave (1610-1644). We present evidence to validate the first drawing of the maned sloth, completed 206 years before the official taxonomic description. PMID- 27556225 TI - Technique of spinal cord compression induced by inflation of epidural balloon catheter in rabbits (Oryctologus cuniculus): efficient and easy to use model. AB - The most common cause of spinal cord injury are high impact trauma, which often result in some motor impairment, sensory or autonomic a greater or lesser extent in the distal areas the level of trauma. In terms of survival and complications due to sequelae, veterinary patients have a poor prognosis unfavorable. Therefore justified the study of experimental models of spinal cord injury production that could provide more support to research potential treatments for spinal cord injuries in medicine and veterinary medicine. Preclinical studies of acute spinal cord injury require an experimental animal model easily reproducible. The most common experimental animal model is the rat, and several techniques for producing a spinal cord injury. The objective of this study was to describe and evaluate the effectiveness of acute spinal cord injury production technique through inflation of Fogarty(r) catheter using rabbits as an experimental model because it is a species that has fewer conclusive publications and contemplating. The main requirements of a model as low cost, handling convenience, reproducibility and uniformity. The technique was adequate for performing preclinical studies in neuro-traumatology area, effectively leading to degeneration and necrosis of the nervous tissue fostering the emergence of acute paraplegia. PMID- 27556226 TI - Nasal carriage of resistant Staphylococcus aureus in a medical student community. AB - Staphylococcus aureus can cause a variety of infections due to its high transmissibility, high pathogenic potential and resistance to multiple drugs, factors that contribute to the relevance of infections in healthcare services. The aim of this study was to document phenotypic and genotypic resistance factors of Staphylococcus aureus strains, isolated from nasal mucosa of medical students. A nasal swab was collected from the nares (nostrils) of 222 medical students. After collection, the samples were submitted to isolation and identification procedures. From 204 valid samples, 20.6% (42 samples) were positive for S. aureus. For the assessment of phenotypic resistance by disk-diffusion technique, from 42 samples, 95.2% showed resistance to erythromycin, 42.8% to clindamycin, 16.6% to cephoxitin and 9.5% to oxacillin. The D test showed that 26.2% of samples were resistant to macrolides, lincosamides and streptogramin B. A PCR assay allowed for the evaluation of a genotypic resistance profile, in which 16.6% of the samples were positive for the mecA gene, 35.7% positive for the ermC gene or ermA gene and 28.5% were positive for both genes. These results demonstrate that medical students can enter the healthcare service previously colonized by multidrug resistant strains and become potential spreaders in the hospital environment. PMID- 27556227 TI - Expanding the knowledge of the chemical structure of glycoconjugates from Trypanosoma cruzi TcI genotype. Contribution to taxonomic studies. AB - One of the main obstacles to the treatment of Chagas disease is the genetic and phenotypical variance displayed by T. cruzi strains, resulting in differences in morphology, virulence, pathogenicity and drug susceptibility. To better understand the role of glycoconjungates in Chagas disease, we performed the molecular characterization of the O-linked chains from mucins and glycoinositolphospholipids (GIPLs) of the Silvio X10 clone 1 strain. We demonstrated the presence of a beta-galactofuranose (beta-Galf) unity linked to the O-4 position of the alpha-N-acetylglucosamine (alpha-GlcNAc)O-4 in Tc-mucins. GIPLs analysis showed that the lipidic portion is exclusively composed of ceramide and the PI-oligossacharidic portion contains the Man4(AEP)GlcN-Ins-PO4 core, substituted by ethanolamine-phosphate (EtNP) on the third distal mannose from inositol, which may or may not have a terminal beta Galf unity. These results confirm the classification of the Silvio X10/1 strain in group T. cruzi I. Again, it is noted that the study of T. cruzi surface glycoconjugates confirm the molecular results and the hypothesis that surface glycoconjugates may be interesting biomarker for the differentiation of trypanosomatid strains. PMID- 27556228 TI - MicroRNA-144 regulates cancer cell proliferation and cell-cycle transition in acute lymphoblastic leukemia through the interaction of FMN2. AB - BACKGROUND: In the present study, we explored the functional roles of microRNA 144 (miR-144) upregulation and downregulation in human acute lymphoblastic leukemia (ALL). METHODS: Gene expression of miR-144 was examined using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in both ALL cell lines and T-leukemic cells of ALL patients. In ALL cell lines Molt-3 and Jurkat cells, miR-144 was either upregulated or downregulated through lentiviral transduction. The subsequent effects of miR-144 upregulation or downregulation on ALL proliferation, cell-cycle transition and in vivo xenograft were assessed. A possible downstream target of miR-144, human formin-2 (FMN2), was assessed by a dual-luciferase activity assay, qRT-PCR and western blotting. FMN2 was then overexpressed in miR-144-upregulated Molt-3 and Jurkat cells to determine its effect on miR-144 induced tumor suppression on ALL proliferation and cell-cycle transition. RESULTS: MiR-144 was significantly downregulated in both ALL cell lines and T-leukemic cells of ALL patients. Lentiviral transfection successfully induced miR-144 upregulation or downregulation in Molt-3 and Jurkat cells without affecting cell viability. Functional assays demonstrated that miR-144 upregulation suppressed ALL proliferation and cell-cycle transition in vitro, as well as the growth of Jurkat xenograft in vivo, whereas miR-144 downregulation had no functional effect on ALL development. Multiple approaches confirmed that FMN2 was the downstream target of miR-144 in ALL. Finally, overexpressing FMN2 reversed the inhibitory effects of miR-144-upregulation on ALL proliferation and cell-cycle transition. CONCLUSIONS: MiR-144 functions as a tumor suppressor in ALL, very likely through the inverse regulation of its target gene FMN2. PMID- 27556230 TI - Novel TPLO Alignment Jig/Saw Guide Reproduces Freehand and Ideal Osteotomy Positions. AB - OBJECTIVES: To evaluate the ability of an alignment jig/saw guide to reproduce appropriate osteotomy positions in the tibial plateau leveling osteotomy (TPLO) in the dog. METHODS: Lateral radiographs of 65 clinical TPLO procedures using an alignment jig and freehand osteotomy performed by experienced TPLO surgeons using a 24 mm radial saw blade between Dec 2005-Dec 2007 and Nov 2013-Nov 2015 were reviewed. The freehand osteotomy position was compared to potential osteotomy positions using the alignment jig/saw guide. The proximal and distal jig pin holes on postoperative radiographs were used to align the jig to the bone; saw guide position was selected to most closely match the osteotomy performed. The guide-to-osteotomy fit was categorized by the distance between the actual osteotomy and proposed saw guide osteotomy at its greatest offset (<=1 mm = excellent; <=2 mm = good; <=3 mm = satisfactory; >3 mm = poor). RESULTS: Sixty four of 65 TPLO osteotomies could be matched satisfactorily by the saw guide. Proximal jig pin placement 3-4 mm from the joint surface and pin location in a craniocaudal plane on the proximal tibia were significantly associated with the guide-to-osteotomy fit (P = 0.021 and P = 0.047, respectively). CLINICAL SIGNIFICANCE: The alignment jig/saw guide can be used to reproduce appropriate freehand osteotomy position for TPLO. Furthermore, an ideal osteotomy position centered on the tibial intercondylar tubercles also is possible. Accurate placement of the proximal jig pin is a crucial step for correct positioning of the saw guide in either instance. PMID- 27556231 TI - Should psoriasis be considered a risk factor for hypogonadism in male patients? A monocentric, prospective, observational pilot study. PMID- 27556232 TI - Do Radiologists and Surgeons Speak the Same Language? A Retrospective Review of Facial Trauma. AB - OBJECTIVE: The objective of the present study is to examine the concordance of facial fracture classifications in patients with trauma who underwent surgery and to assess the epidemiologic findings associated with facial trauma. MATERIALS AND METHODS: Patients with trauma who underwent facial CT examination and inpatient operative intervention during a 1-year period were retrospectively analyzed. Patient demographic characteristics, the mechanism of injury, the radiology report, the surgical diagnosis, and clinical indications were reviewed. Fractures were documented according to bone type and were classified into the following subtypes: LeFort 1, LeFort 2, LeFort 3, naso-orbital-ethmoidal, zygomaticomaxillary complex (ZMC), orbital, and mandibular. Concordance between the radiology and surgery reports was assessed. RESULTS: A total of 115,000 visits to the emergency department resulted in 9000 trauma activations and 3326 facial CT examinations. One hundred fifty-six patients (4.7%) underwent facial surgical intervention, and 133 cases met criteria for inclusion in the study. The mean injury severity score was 10.2 (range, 1-75). The three most frequently noted injury mechanisms were as follows: assault (77 cases [57.9%]), a traffic accident (21 cases [15.8%]), and a fall (20 cases [15%]). The three most frequently noted facial bone fractures were as follows: mandible (100 cases [75.2%]), maxilla (53 cases [39.8%]), and orbit (53 cases [39.8%]). The five descriptors most frequently found in the radiology and surgery reports were the mandibular angle (25 cases), the orbital floor (25 cases), the mandibular parasymphysis (22 cases), the mandibular body (21 cases), and ZMC fractures (19 cases). A classification was not specified in 31 of the radiologic impressions (22.5%), with 28 of 31 radiologists expecting the surgeon to read the full report. The descriptors used in the radiology and surgery reports matched in 73 cases (54.9%) and differed in 51 cases (38.3%). No classifications were used by one or both specialties in nine cases (6.8%). CONCLUSION: For 38.3% of patients needing facial surgery, descriptors used in the radiologic and surgery reports differed. Speaking a common language can potentially improve communication between the radiology and surgery services and can help expedite management of cases requiring surgery. PMID- 27556233 TI - Changes in the Floating Plastic Pollution of the Mediterranean Sea in Relation to the Distance to Land. AB - The composition, size distribution, and abundance of floating plastic debris in surface waters of the Mediterranean Sea were analyzed in relation to distance to land. We combined data from previously published reports with an intensive sampling in inshore waters of the Northwestern Mediterranean. The highest plastic concentrations were found in regions distant from from land as well as in the first kilometer adjacent to the coastline. In this nearshore water strip, plastic concentrations were significantly correlated with the nearness to a coastal human population, with local areas close to large human settlements showing hundreds of thousands of plastic pieces per km2. The ratio of plastic to plankton abundance reached particularly high values for the coastal surface waters. Polyethylene, polypropylene and polyamides were the predominant plastic polymers at all distances from coast (86 to 97% of total items), although the diversity of polymers was higher in the 1-km coastal water strip due to a higher frequency of polystyrene or polyacrylic fibers. The plastic size distributions showed a gradual increase in abundance toward small sizes indicating an efficient removal of small plastics from the surface. Nevertheless, the relative abundance of small fragments (< 2 mm) was higher within the 1-km coastal water strip, suggesting a rapid fragmentation down along the shoreline, likely related with the washing ashore on the beaches. This study constitutes a first attempt to determine the impact of plastic debris in areas closest to Mediterranean coast. The presence of a high concentration of plastic including tiny plastic items could have significant environmental, health and economic impacts. PMID- 27556229 TI - Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. AB - The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P<=8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive. PMID- 27556235 TI - Sensitivity and specificity of normality tests and consequences on reference interval accuracy at small sample size: a computer-simulation study. AB - BACKGROUND: According to international guidelines, parametric methods must be chosen for RI construction when the sample size is small and the distribution is Gaussian. However, normality tests may not be accurate at small sample size. OBJECTIVES: The purpose of the study was to evaluate normality test performance to properly identify samples extracted from a Gaussian population at small sample sizes, and assess the consequences on RI accuracy of applying parametric methods to samples that falsely identified the parent population as Gaussian. METHODS: Samples of n = 60 and n = 30 values were randomly selected 100 times from simulated Gaussian, lognormal, and asymmetric populations of 10,000 values. The sensitivity and specificity of 4 normality tests were compared. Reference intervals were calculated using 6 different statistical methods from samples that falsely identified the parent population as Gaussian, and their accuracy was compared. RESULTS: Shapiro-Wilk and D'Agostino-Pearson tests were the best performing normality tests. However, their specificity was poor at sample size n = 30 (specificity for P < .05: .51 and .50, respectively). The best significance levels identified when n = 30 were 0.19 for Shapiro-Wilk test and 0.18 for D'Agostino-Pearson test. Using parametric methods on samples extracted from a lognormal population but falsely identified as Gaussian led to clinically relevant inaccuracies. CONCLUSIONS: At small sample size, normality tests may lead to erroneous use of parametric methods to build RI. Using nonparametric methods (or alternatively Box-Cox transformation) on all samples regardless of their distribution or adjusting, the significance level of normality tests depending on sample size would limit the risk of constructing inaccurate RI. PMID- 27556236 TI - Asymptomatic Atherosclerosis in Primary Sjogren Syndrome: Correlation Between Low Ankle Brachial Index and Autoantibodies Positivity. AB - BACKGROUND: Primary Sjogren syndrome is a chronic inflammatory autoimmune disease. The delay in diagnosis allows the establishment of a chronic inflammatory state, which makes primary Sjogren syndrome an interesting model for the study of atherosclerosis. OBJECTIVES: The aim of this study was to evaluate subclinical atherosclerosis in 49 patients with Sjogren syndrome using noninvasive methods. METHODS: We assessed traditional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and family history of atherosclerosis. Patients with prior cardiovascular events and a history of atherosclerosis were excluded. Clinical and laboratory features were recorded, as well as the European League Against Rheumatism Sjogren's Syndrome Activity Index calculation. The atherosclerosis evaluation was done by carotid intima-media thickness, measured by ultrasonography, and ankle-brachial index (ABI). RESULTS: Fifteen patients (31%) had at least 1 traditional risk factor, and 65.3% had a European League Against Rheumatism Sjogren's Syndrome Activity Index score from mild to moderate. Only 2 patients had increased carotid intima-media thickness. However, 59% presented ABI alterations. Multiple correspondence analysis showed a clear correlation between low ABI and the positivity of autoantibodies (antinuclear antibodies, anti-SSA, rheumatoid factor). CONCLUSIONS: The subgroup of patients with positive autoantibodies showed low ABI, which may represent a higher risk of early atherosclerosis and indicate the need for more careful monitoring in this group. PMID- 27556237 TI - Rheumatologists' Approaches to Diagnosis and Treatment of Depression. AB - OBJECTIVE: We examined rheumatologists' approaches to and perceptions of depression in everyday practice. METHODS: A questionnaire was mailed to 470 practicing rheumatologists in California; 226 were included in the final analyses. Respondents provided information on demographics, practice characteristics, and attitudes, perceptions, and practices related to depression. Logistic regression models were constructed to assess the relationship of rheumatologists' personal and practice characteristics with their depression related practices. RESULTS: Fifty-one percent of respondents reported that at least half of their patients had depression. Nearly all providers (99%) reported addressing mental health issues during some visits. Rheumatologists were about equally likely to prescribe antidepressants, refer to a psychiatrist, or return the patient to the primary care physician, with roughly 60% often applying each of the 3 strategies. Respondents identified access to services and patients' resistance to mental health diagnoses as major barriers to effective depression management. In logistic regression models, greater number of patient visits per week, greater percentage of patients with fibromyalgia, and private practice setting were associated with more prescription of antidepressants (P < 0.05). CONCLUSIONS: Depression is common in rheumatologic practice, yet systems for identification, treatment, and referral of depressed patients are not universal. Rheumatologists' awareness of the need for mental health services is high, but they may lack the confidence, time, and/or referral networks to provide consistently effective care for depressed patients. Improving depression care in rheumatology may require a combination of clinician-level interventions (e.g., enhanced behavioral health training) and practice-level reforms (e.g., collaborative care). PMID- 27556234 TI - Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations. AB - RATIONALE: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined. OBJECTIVES: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA. METHODS: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (>=3). Replication of a multivariable model was performed with data from the SARP-1 + 2 cohort. MEASUREMENTS AND MAIN RESULTS: Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2-2.1] for every log unit of eosinophils, 1.3 [1.1-1.4] for every 10 body mass index units, and 1.2 [1.1-1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4-2.1] and 1.6 [1.3 2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP-1 + 2 multivariable model. CONCLUSIONS: EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915). PMID- 27556238 TI - Low-Density Lipoprotein Cholesterol Is Associated With Asymptomatic Sensorineural Hearing Loss in Patients With Systemic Lupus Erythematosus. AB - OBJECTIVE: The aims of this study were to determine the frequency of asymptomatic sensorineural hearing loss (SNHL) in systemic lupus erythematosus (SLE) and to determine the association between SNHL and demographic, clinical, and laboratory features and cardiovascular risk factors. METHODS: We conducted a cross-sectional study including consecutive female SLE patients. We performed audiometry and clinical and laboratory evaluation and determined cardiovascular risk factors in all patients. Statistical analysis included principal component analysis and logistic regression. RESULTS: Eighty-nine women were included with mean age of 38.98 (SD, 7.77) years and mean disease duration of 10.29 (SD, 9.19) years. Asymptomatic SNHL was observed in 14 patients (16%). In logistic regression model, only low-density lipoprotein levels (z = 2.64; P = 0.008) were associated with SNHL. CONCLUSIONS: We observed asymptomatic SNHL in 16% of SLE and an association with low-density lipoprotein levels suggesting atherosclerosis as a mechanism. Follow-up is needed to determine clinical implications. PMID- 27556239 TI - Rheumatologists and Ophthalmologists Differ in Treatment Decisions for Ocular Behcet Disease. AB - BACKGROUND: Ocular involvement in patients with Behcet disease represents a significant clinical morbidity in this disease, and the prevention of visual impairment is an important treatment goal. There are no randomized controlled trials for the treatment of ocular Behcet disease; however, clinicians must still make treatment decisions. OBJECTIVES: The goals of this study were to describe the treatment preferences of rheumatologists and ophthalmologists for the treatment of ocular Behcet disease and to identify factors that influence these decisions. METHODS: Eight hundred fifty-two rheumatologists and 934 ophthalmologists were surveyed via e-mail regarding their choice of therapy for a hypothetical patient with ocular Behcet disease. Respondents were asked to select first- and second-choice therapies and then reselect first and second choices assuming there would be no issues with cost or insurance prior authorization. RESULTS: One hundred thirty two physicians (7.4%) who were willing to recommend treatment completed the survey: 68 rheumatologists and 64 ophthalmologists. The most common first-choice therapy for both specialties was a biologic agent. Significantly more rheumatologists than ophthalmologists chose methotrexate (P < 0.025) and azathioprine (P < 0.005) as their first-choice therapy. After assuming there were no concerns with cost or prior authorization, rheumatologists were still more likely to choose azathioprine compared with ophthalmologists (P < 0.02), and ophthalmologists were more likely to choose local steroid implants (P < 0.02). Both rheumatologists and ophthalmologists increased their choice of an anti-tumor necrosis factor agent when cost and prior authorization issues were removed (P < 0.0001 and 0.008, respectively). CONCLUSIONS: Physician decision making is influenced by medical specialty and concerns regarding cost and prior authorization. PMID- 27556240 TI - Use of Eculizumab in Atypical Hemolytic Uremic Syndrome, Complicating Systemic Lupus Erythematosus. AB - Atypical hemolytic uremic syndrome is characterized by the presence of thrombocytopenia, microangiopathic hemolytic anemia, and end-organ injury. In this report, we describe two patients with systemic lupus erythematosus who presented with findings compatible with atypical hemolytic uremic syndrome, complicated by acute kidney injury that was refractory to conventional therapies. Both patients exhibited a response to eculizumab, a monoclonal antibody to complement protein C5, with stabilization of their platelet count. On 1-year follow-up from their initial presentation, their hematologic disease remained in remission without recurrence. PMID- 27556241 TI - Role of Ultrasonography in Knee Osteoarthritis. AB - Ultrasound has become popular among rheumatologists as the first-choice imaging investigation for the evaluation and monitoring of osteoarthritis (OA). Because of recent improvement in technology, ultrasound has the ability to demonstrate and assess the minimal structural abnormalities, which involve the pathophysiology and progression of OA, such as articular cartilage, synovial tissue, bony cortex, and other soft tissue. Nowadays, ultrasonography is a promising technique for assessing soft tissue abnormalities such as joint effusion, synovial hypertrophy, Baker cyst, and other structural changes including the decrease in cartilage thickness, meniscus bulging, and formation of osteophyte. Ultrasonography not only possesses diagnostic potential in knee OA but also reveals long-term predictability for disease progress as imaging biomarker. Ultrasonography has also been proven as a useful tool in guiding therapeutic interventions and monitoring treatment effectiveness. This review addresses the utility, reliability, and potential utilization of ultrasonography as an imaging technique in knee OA. PMID- 27556242 TI - Back Pain Due to Fracture of a Sacral Syndesmophyte in Ankylosing Spondylitis. PMID- 27556243 TI - Subungual Glomus Tumor. PMID- 27556244 TI - Digital Tophaceous Gout. PMID- 27556245 TI - Bizarre Parosteal Osteochondromatous Proliferation. PMID- 27556246 TI - Pain Name. PMID- 27556247 TI - Systemic Lupus Erythematosus Onset Seven Years After Initiation of Highly Active Antiretroviral Therapy in a Patient With Human Immunodeficiency Virus: Literature Review and Update on Disease Mechanism of This Unusual Presentation. PMID- 27556248 TI - Methotrexate-Associated Classic Hodgkin Lymphoma in a Patient With Dermatomyositis. PMID- 27556249 TI - Improvement of Articular Pain, Stiffness, and Function in Obese Patients Submitted to Bariatric Surgery. PMID- 27556250 TI - Patient specific computational models to optimize surgical correction for flatfoot deformity. AB - Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of AAFD to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models' behavior was governed solely by patient bodyweight, soft tissue constraints, muscle loading, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. All procedures incorporated first a tendon transfer and then included one hindfoot procedure, the Medializing Calcaneal Osteotomy (MCO), and one of three lateral column procedures: Evans osteotomy, Calcaneocuboid Distraction Arthrodesis (CCDA), Z osteotomy, and the combination procedures MCO & Evans osteotomy, MCO & CCDA, and MCO & Z osteotomy. The combination MCO & Evans and MCO & Z procedures were shown to provide the greatest amount of correction for both forefoot abduction and hindfoot valgus. However, these two procedures significantly increased joint contact force, specifically at the calcaneocuboid joint, and ground reaction force along the lateral column. With exception to the lateral bands of the plantar fascia and middle spring ligament, the strain present in the plantar fascia, spring, and deltoid ligaments decreased after all procedures. The use of patient specific computational models provided the ability to investigate effects of alternate surgical corrections on restoring biomechanical function in these flatfoot patients. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1523-1531, 2017. PMID- 27556251 TI - Patterns of olfactory impairment reflect underlying disease etiology. AB - OBJECTIVE: We aimed to determine whether the pattern of olfactory impairment seen in psychophysical testing reflects underlying disease etiology. STUDY DESIGN: Retrospective cohort. METHODS: We performed a retrospective analysis of 1,226 patients from our tertiary referral center. Only hyposmic patients with the following conditions were included: postinfectious hyposmia, posttraumatic hyposmia, hyposmia secondary to sinonasal disease, and hyposmia secondary to Parkinson disease. Patients with anosmia were excluded. RESULTS: Using a repeated measures analysis of variance (within subject factor "test": threshold [T], discrimination [D], identification [I]; between subject factor: "etiology") with posthoc Bonferroni corrected t tests, we found significant interaction between the factors "test" and "etiology" (F6,2444 = 8.46, P < 0.001), indicating that different causes of hyposmia produce different patterns of olfactory loss with respect to the individual subtests T, D, and I . Specifically, patients with Parkinson disease performed relatively well in odor threshold testing, but poorly in odor identification and discrimination compared with the other etiology groups. Conversely, patients with sinonasal disease performed well in odor identification and discrimination but poorly in odor threshold. Patients with postinfectious and posttraumatic hyposmia performed relatively well in both thresholds and discrimination but poorly in identification. However, patients with posttraumatic hyposmia had globally reduced scores compared with the other groups. CONCLUSION: This is the first study to comprehensively show that patterns of olfactory impairment reflect underlying disease etiology. We suggest that multicomponent olfactory testing should be performed, especially if there is diagnostic uncertainty. However, to clearly separate different patterns of olfactory loss to the various causes at an individual level, more work is needed. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016 127:291-295, 2017. PMID- 27556253 TI - An International Asset Map of Clinicians, Educators, and Researchers Pursuing Better Medicine Use in Children: Initial Findings. AB - The world's 1.89 billion children (age 0-14) too frequently receive treatments that have not been validated through clinical pharmacology research, especially in low- and middle-income countries. Initial findings from an international asset map of professionals and clinician scientists available to address the needs for education, research, and treatment support suggest a critical shortage of clinical pharmacologists, clinical pharmacists, and other professionals with advanced training in the evaluation of therapies for childhood conditions and illnesses. A total of 497 individuals responded to a survey conducted between May 2015 and February 2016. An alarming signal is apparent showing that, while the overall resource pool is unquestionably limited, 87% of relevant qualified personnel are located in high-income countries. The data suggest an urgent need for targeted training in pediatric clinical pharmacology, with particular focus on the needs in Africa, Latin America, and most of Asia. PMID- 27556252 TI - Comparative Methylome Analysis of the Occasional Ruminant Respiratory Pathogen Bibersteinia trehalosi. AB - We examined and compared both the methylomes and the modification-related gene content of four sequenced strains of Bibersteinia trehalosi isolated from the nasopharyngeal tracts of Nebraska cattle with symptoms of bovine respiratory disease complex. The methylation patterns and the encoded DNA methyltransferase (MTase) gene sets were different between each strain, with the only common pattern being that of Dam (GATC). Among the observed patterns were three novel motifs attributable to Type I restriction-modification systems. In some cases the differences in methylation patterns corresponded to the gain or loss of MTase genes, or to recombination at target recognition domains that resulted in changes of enzyme specificity. However, in other cases the differences could be attributed to differential expression of the same MTase gene across strains. The most obvious regulatory mechanism responsible for these differences was slipped strand mispairing within short sequence repeat regions. The combined action of these evolutionary forces allows for alteration of different parts of the methylome at different time scales. We hypothesize that pleiotropic transcriptional modulation resulting from the observed methylomic changes may be involved with the switch between the commensal and pathogenic states of this common member of ruminant microflora. PMID- 27556255 TI - In This Issue * September 1, 2016. PMID- 27556256 TI - Navigating the future with purpose and certainty. PMID- 27556254 TI - Risk stratification model to detect early pulmonary disease in infants with cystic fibrosis diagnosed by newborn screening. AB - OBJECTIVE: The clinical benefit of newborn screening (NBS) for cystic fibrosis (CF) has been primarily nutritional, with less overt respiratory impact. Identification of risk factors for infant CF lung disease could facilitate targeted interventions to improve pulmonary outcomes. METHODS: This retrospective study evaluated socioeconomic information, clinical data, and results from routine infant pulmonary function testing (iPFT) of infants diagnosed with CF through NBS (N = 43) at a single CF center over a 4-year period (2008-2012). A five-item composite clinical score was developed and combined with socioeconomic indicators to facilitate identification of CF infants at increased risk of early onset respiratory impairment. RESULTS: Paternal education was positively associated with lung function (P = 0.02). Clinical score <7 (on a scale of 0-10) predicted diminished pulmonary measure (P < 0.005). Retrospective risk stratification by clinical score and paternal education identified CF infants at low, intermediate, or high risk of pulmonary disease. Forced expiratory volume (FEV0.5 %, mean +/- SD) averaged 115 +/- 19% in the low-risk group, 97 +/- 17% in the intermediate-risk group, and 90 +/- 8% in the high-risk group (P < 0.005). Results were similar for mid-expiratory flows (FEF25-75 %). Multiple regression analysis confirmed the predictive value of this risk stratification model of CF infant pulmonary health. CONCLUSION: We combined socioeconomic and clinical data to risk-stratify CF infants for early-onset lung disease as quantified by iPFT. Our model showed significant differences in infant pulmonary function across risk groups. The developed tool offers an easily available, inexpensive, and non invasive way to assess risk of respiratory decline in CF infants and identify those meriting targeted therapeutic attention. Pediatr Pulmonol. 2016;51:1168 1176. (c) 2016 Wiley Periodicals, Inc. PMID- 27556258 TI - Letters to the Editor. PMID- 27556259 TI - What Is Your Diagnosis? PMID- 27556260 TI - Pathology in Practice. PMID- 27556261 TI - Pathology in Practice. PMID- 27556262 TI - Characteristics of cats sterilized through a subsidized, reduced-cost spay-neuter program in Massachusetts and of owners who had cats sterilized through this program. AB - OBJECTIVE To determine characteristics of cats sterilized through a subsidized, reduced-cost spay-neuter program in Massachusetts and of owners who had their cats sterilized through this program. DESIGN Cross-sectional anonymous survey and telephone interviews. SAMPLE 1,188 (anonymous surveys) and 99 (telephone interviews) cat owners. PROCEDURES Owners who had a cat sterilized at clinics held between January 2006 and December 2008 were invited to complete anonymous surveys. Semistructured telephone interviews were conducted with owners who had a cat sterilized during clinics held in 2009. RESULTS Most cats had never been seen by a veterinarian previously; "too expensive" was the most common reason for this. Total annual household income was significantly associated with the number of times the cat had been examined by a veterinarian and reason why the cat had not been spayed or neutered previously. Most cats were acquired through informal means and without actively being sought, and there was often a time lag between acquisition and sterilization. Undesirable behavior and avoiding pregnancy were primary motivations for neutering and spaying, respectively. Nearly half of owners who indicated they would have had their cat sterilized through a private veterinarian if the clinic had not been available stated that the surgery would have been delayed because of cost. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that spay-neuter decisions were related to owner income and procedure cost, that elimination of the reduced-cost spay-neuter program would likely have exacerbated the spay-delay problem, and that gradations of financial need should be considered when evaluating relationships between income and spay-neuter decisions. PMID- 27556263 TI - Impact of a chapter book and collectible cards describing the lives of seven veterinarians on third-grade students' career aspirations and expectations. AB - OBJECTIVE To determine the impact of exposure to a chapter book and collectible cards describing the lives of 7 veterinarians on career aspirations and expectations of third-grade students. DESIGN Survey. SAMPLE 176 third-grade students from 6 schools in Indiana. PROCEDURES Students responded to a questionnaire by stating their career aspirations and expectations before and within 8 days after classroom exposure to the chapter book and collectible cards. RESULTS As a group, significantly more students answered that they would like or expect to be a veterinarian when they are an adult after exposure to the book and cards. By gender, more boys, but not girls, answered that they would like or expect to be a veterinarian after exposure to the book and cards. Additionally, more White students and more rural students answered that they expected to be a veterinarian after exposure to the book and cards. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that young children's career aspirations and expectations can be influenced, at least in the short term, by exposure to educational materials about veterinary medicine when delivered as part of a classroom curriculum. PMID- 27556264 TI - Correction: Sedation and mechanical hypoalgesia after sublingual administration of detomidine hydrochloride gel to donkeys. PMID- 27556265 TI - Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs. AB - OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug. PMID- 27556266 TI - Evaluation of peripheral blood and abdominal fluid variables as predictors of intestinal surgical site failure in dogs with septic peritonitis following celiotomy and the placement of closed-suction abdominal drains. AB - OBJECTIVE To evaluate peripheral blood and abdominal fluid variables as predictors of intestinal surgical site failure in dogs with septic peritonitis following celiotomy and closed-suction abdominal drain (CSAD) placement. DESIGN Prospective study. ANIMALS 26 dogs with septic peritonitis that underwent celiotomy and CSAD placement. PROCEDURES Abdominal fluid and blood samples were collected prior to surgery and daily thereafter until CSAD removal. Abdominal fluid was collected through the CSAD. Analysis of all samples included pH, PCO2, PO2, PCV, WBC count, and total solids, glucose, lactate, and electrolyte concentrations. Abdominal fluid samples also underwent cytologic evaluation and bacterial culture, and the volume of fluid removed through the drain was recorded daily. The blood-to-fluid glucose and lactate differences, fluid-to-blood lactate ratio and blood-to-fluid WBC and neutrophil ratios were determined daily. Dogs were categorized into 2 groups on the basis of whether they had an uneventful recovery (UR) or developed postoperative septic peritonitis (POSP). RESULTS 23 dogs had a UR and 3 developed POSP. On the third day after surgery, the abdominal fluid WBC count was significantly lower and the blood-to-fluid WBC and neutrophil ratios were significantly higher for dogs in the POSP group, compared with those for dogs in the UR group. None of the other blood and abdominal fluid variables assessed differed significantly between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Results failed to identify any objective predictive indicators for POSP in dogs with CSADs. Use of blood-to-fluid WBC and neutrophil ratios as predictive indicators for POSP requires further investigation. PMID- 27556267 TI - Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006-2013). AB - OBJECTIVE To evaluate outcomes for cats treated with orally administered famciclovir 3 times/d for clinical signs attributed to naturally occurring feline herpesvirus type 1 (FHV-1) infection and to assess variables related to owner satisfaction with the treatment. DESIGN Retrospective case series. ANIMALS 59 client-owned cats. PROCEDURES Medical records were reviewed to identify cats treated for presumed FHV-1 infection from 2006 through 2013 with >= 1 follow-up visit. Signalment, duration of clinical signs, prior treatment, examination findings, diagnostic test results, concurrent treatments, and outcome data were recorded. Owners were asked to complete a survey regarding patient- and treatment related variables. Data were compared between cats that received low (approx 40 mg/kg [18 mg/lb]) and high (approx 90 mg/kg [41 mg/lb]) doses of famciclovir, PO, 3 times/d. RESULTS Patient age ranged from 0.03 to 16 years. Conjunctivitis (51/59 [86%]), keratitis (51 [86%]), blepharitis (19 [32%]), nasal discharge or sneezing (10 [17%]), and dermatitis (4 [7%]) were common findings. Clinical improvement was subjectively graded as marked in 30 (51%) cats, mild in 20 (34%), and nonapparent in 9 (15%). Median time to improvement was significantly shorter, and degree of improvement was significantly greater in the highdose group than in the low-dose group. Adverse effects potentially attributable to famciclovir administration were reported for 10 cats. On the basis of survey responses, most (29/32 [91%]) owners were satisfied with their cat's treatment. CONCLUSIONS AND CLINICAL RELEVANCE Famciclovir at the prescribed dosages was associated with improved clinical signs in cats with presumed FHV-1 infection, and few adverse effects were attributed to the treatment. Further studies are needed to assess whether a famciclovir dosage of 90 versus 40 mg/kg, PO, 3 times/d would result in increased efficacy and shorter treatment time. PMID- 27556268 TI - Early diagnostic imaging findings in juvenile dogs with presumed diskospondylitis: 10 cases (2008-2014). AB - OBJECTIVE To describe early diagnostic imaging findings in juvenile dogs with diskospondylitis. DESIGN Retrospective case series. ANIMALS 10 client-owned dogs < 6 months of age. PROCEDURES Medical records were searched to identify juvenile dogs with a presumptive diagnosis of diskospondylitis. Signalment, history, examination findings, diagnostic test results, and imaging procedures were reviewed. Archived diagnostic images were retrieved and retrospectively evaluated. Data analysis was descriptive. RESULTS All dogs were evaluated for signs of vertebral pain <= 3 weeks after treatment for blunt trauma, bite wounds, or systemic illness. The earliest radiographic change was a narrowed intervertebral disk space (found for 28 disk spaces <= 2 weeks after evaluation for signs of vertebral pain); subluxation of adjacent vertebrae was identified for 8 of 28 affected disks, either initially or within the following 2 weeks. Vertebral end plate lysis was not an initial radiographic feature but was evident in follow-up radiographs. Ultrasonographic and transverse, multiformatted, volume rendered CT images were obtained for 5 and 4 dogs, respectively. Ultrasonographic changes included ventrally bulging hypoechoic material at the affected disk site and loss of typical normal reverberation artifact in 4 dogs; these were detected prior to radiographic changes in 2 dogs. Affected disks on volume-rendered CT images had altered coloration in 3 of 4 dogs, and this was identified prior to radiographic changes in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE Juvenile dogs with a presumptive diagnosis of diskospondylitis had early imaging findings that were atypical, compared with the changes described for adult dogs with this condition. PMID- 27556269 TI - Defining the primary research question in veterinary clinical studies. AB - A thoughtful, clearly defined research question should be the foundation of any clinical trial or research study. The research question helps determine key study methods, and defining a specific research question helps avoid problems with inadequate sample size, inappropriate design, or multiple statistical comparisons. Rationales and strategies for formulating research questions and using them to define study protocols are discussed, with a focus on application in clinical trials. PMID- 27556270 TI - Self-injury Mortality in the United States in the Early 21st Century: A Comparison With Proximally Ranked Diseases. AB - Importance: Fatal self-injury in the United States associated with deliberate behaviors is seriously underestimated owing to misclassification of poisoning suicides and mischaracterization of most drug poisoning deaths as "accidents" on death certificates. Objective: To compare national trends and patterns of self injury mortality (SIM) with mortality from 3 proximally ranked top 10 causes of death: diabetes, influenza and pneumonia, and kidney disease. Data, Setting, and Participants: Underlying cause-of-death data from 1999 to 2014 were extracted for this observational study from death certificate data in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research online databases. Linear time trends were compared by negative binomial regression with a log link function. Self-injury mortality was defined as a composite of suicides by any method and estimated deaths from drug self intoxication whose manner was an "accident" or was undetermined. Main Outcomes and Measures: Mortality rates and ratios, cumulative mortality in individuals younger than 55 years, and years of life lost in 2014. Results: There were an estimated 40 289 self-injury deaths in 1999 and 76 227 in 2014. Females comprised 8923 (22.1%) of the deaths in 1999 and 21 950 (28.8%) of the 76 227 deaths in 2014. The estimated crude rate for SIM increased 65% between 1999 and 2014, from 14.4 to 23.9 deaths per 100 000 persons (rate ratio, 1.03; 95% CI, 1.03-1.04; P < .001). The SIM rate continuously exceeded the kidney disease mortality rate and surpassed the influenza and pneumonia mortality rate by 2006. By 2014, the SIM rate converged with the diabetes mortality rate. Additionally, the SIM rate was 1.8-fold higher than the suicide rate in 2014 vs 1.4-fold higher in 1999. The male-to-female ratio for SIM decreased from 3.7 in 1999 to 2.6 in 2014 (male by year: rate ratio, 0.98; 95% CI, 0.97-0.98; P < .001). By 2014, SIM accounted for 32.2 and 36.6 years of life lost for male and female decedents, respectively, compared with 15.8 and 17.3 years from diabetes, 15.0 and 16.6 years from influenza and pneumonia, and 14.5 and 16.2 years from kidney disease. Conclusions and Relevance: The burgeoning SIM [self-injury mortality] rate has converged with the mortality rate for diabetes, but there is a 6-fold differential in the proportion of SIM vs diabetes deaths involving people younger than 55 years and SIM is increasingly affecting women relative to men. Accurately characterizing, measuring, and monitoring this major clinical and public health challenge will be essential for developing a comprehensive etiologic understanding and evaluating preventive and therapeutic interventions. PMID- 27556271 TI - Transfollicular enhancement of methyl myristate loaded in cationic niosomes incorporated in hair lotion. AB - Hair lotion containing methyl myristate loaded in cationic niosomes (HL-MMnio) composed of Brij72/cholesterol/DDAB at 7:3:0.65 molar ratio was developed. The remaining percentages of MM loaded in cationic niosomes in hair lotion were higher than free MM in hair lotion of about 1.2 times. The cumulative amounts in porcine skin and the receiver compartment of MM loaded in cationic niosomes incorporated in hair lotion were higher than those of free MM in hair lotion of 1.45 and 1.32 times, respectively. HL-MMnio showed very slightly irritation on rabbit skin, which was disappeared after 4 d. For melanogenesis induction in C57BL/6 mice with aged-induced grey body coat hairs, the highest pigmentation scores of HL-MMnio applied on the dorsal area were observed after 21 days, while hair lotion containing the free MM indicated after 35 days. This study has suggested that HL-MMnio was the high potential formulation for canities treatment. PMID- 27556272 TI - An Update on Intradialytic Cardiac Dysfunction. AB - Cardiac dysfunction is a key factor in the high morbidity and mortality rates seen in hemodialysis (HD) patients. Much of the dysfunction is manifest as adverse changes in cardiac and vascular structure prior to commencing dialysis. This adverse vascular remodeling arises as a dysregulation between pro- and antiproliferative signaling pathways in response to hemodynamic and nonhemodynamic factors. The HD procedure itself further promotes cardiomyopathy by inducing hypotension and episodic regional cardiac ischemia that precedes global dysfunction, fibrosis, worsening symptoms, and increased mortality. Drug based therapies have been largely ineffective in reversing HD-associated cardiomyopathy, in part due to targeting single pathways of low yield. Few studies have sought to establish natural history and there is no framework of priorities for future clinical trials. Targeting intradialytic cardiac dysfunction by altering dialysate temperature, composition, or ultrafiltration rate might prevent the development of global cardiomyopathy, heart failure, and mortality through multiple pathways. Novel imaging techniques show promise in characterizing the physiological response to HD that is a unique model of repetitive ischemia-reperfusion injury. Reducing HD-associated cardiomyopathy may need a paradigm shift from empirical delivery of solute clearance to a personalized therapy balancing solute and fluid removal with microvascular protection. This review describes the evidence for intradialytic cardiac dysfunction outlining cardioprotective strategies that extend to multiple organs with potential impacts on exercise tolerance, sleep, cognitive function, and quality of life. PMID- 27556273 TI - Preoperative Assessment of Pancreatic Cancer with FDG PET/MR Imaging versus FDG PET/CT Plus Contrast-enhanced Multidetector CT: A Prospective Preliminary Study. AB - Purpose To determine the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) imaging in the preoperative assessment of pancreatic cancer in comparison with that of FDG PET/computed tomography (CT) plus contrast material-enhanced multidetector CT. Materials and Methods This prospective study was approved by the institutional review board; written informed consent was obtained. Thirty-seven patients with 39 pancreatic tumors underwent preoperative FDG PET/MR imaging, PET/CT, and contrast-enhanced multidetector CT. The authors measured maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) of pancreatic cancer at PET/MR imaging and PET/CT. Two radiologists independently reviewed the two imaging sets (set 1, PET/MR imaging; set 2, PET/CT plus multidetector CT) to determine tumor resectability according to a five-point scale, N stage (N0 or N positive), and M stage (M0 or M1). With use of clinical-surgical-pathologic findings as the standard of reference (n = 20), diagnostic performances of the two imaging sets were compared by using the McNemar test. Results Both SUVmax and SUVmean of pancreatic tumors showed strong correlations between PET/MR imaging and PET/CT (r = 0.897 and 0.890, respectively; P < .001). The diagnostic performance of PET/MR imaging was not significantly different from that of PET/CT plus multidetector CT in the assessment of tumor resectability (area under the receiver operating characteristic curve: 0.891 vs 0.776, respectively, for reviewer 1 [P = .109] and 0.859 vs 0.797 for reviewer 2 [P = .561]), N stage (accuracy: 54% [seven of 13 patients] vs 31% [four of 13 patients]; P = .250 for both reviewers), and M stage (accuracy: 94% [16 of 17 patients] vs 88% [15 of 17 patients] for reviewer 1 [P > .999] and 94% [16 of 17 patients] vs 82% [14 of 17 patients] for reviewer 2 [P = .500]). Conclusion FDG PET/MR imaging showed a diagnostic performance similar to that of PET/CT plus contrast-enhanced multidetector CT in the preoperative evaluation of the resectability and staging of pancreatic tumors. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27556274 TI - Determination of Glomerular Filtration Rate with CT Measurement of Renal Clearance of Iodinated Contrast Material versus 99mTc-DTPA Dynamic Imaging "Gates" Method: A Validation Study in Asymmetrical Renal Disease. AB - Purpose To validate a computed tomographic (CT) glomerular filtration rate (GFR) measurement and compare it with renal dynamic imaging GFR obtained by using the "Gates" method, with dual plasma sampling technetium 99m (99mTc) diethylenetriaminepenta-acetic acid (DTPA) clearance ("true GFR") as the reference standard. Materials and Methods This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Forty-two patients with unilateral renal disease were included. Single-kidney CT GFR was calculated as excretory phase whole-kidney CT number enhancement divided by the area under the time-attenuation curve for the aorta, multiplied by (1 - hematocrit level). The CT GFR was then obtained by summing the result of the two sides. The true GFR and the Gates GFR were measured by using a single injection of 99mTc-DTPA. The CT GFR and Gates GFR were respectively compared with the true GFR by using a paired t test and linear regression analysis. Results The difference between CT GFR (mean +/- standard deviation, 96.02 mL/min +/- 23.11) and true GFR (90.50 mL/min +/- 21.46) was 5.51 mL/min +/- 6.96 (P < .001), demonstrating 6.09% systemic overestimation. The difference between Gates GFR (93.93 mL/min +/- 26.97) and true GFR was 3.42 mL/min +/- 16.10 (P = .176). Linear regression findings confirmed the association between CT GFR (y-axis) and true GFR (x-axis) and between Gates GFR (y-axis) and true GFR (x axis) (P < .001 for both). Both regression lines paralleled the diagonal (intercept = 0 and slope = 1) (P = .599 and P = .945, respectively). The 95% confidence interval of the former was above the diagonal, confirming the systemic overestimation. The standard deviations of residuals of both linear regressions were 7.02 mL/min and 16.30 mL/min, respectively, demonstrating smaller deviation of the CT GFR (P < .001). Conclusion The proposed CT GFR measurement was validated in this study and was proved to be more accurate than the Gates method despite slight (6.09%) systemic overestimation. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27556275 TI - Three-Dimensional Isotropic Fat-Suppressed Proton Density-Weighted MRI at 3 Tesla Using a T/R-Coil Can Replace Multiple Plane Two-Dimensional Sequences in Knee Imaging. AB - PURPOSE: To evaluate whether a 3 D proton density-weighted fat-suppressed sequence (PDwFS) of the knee is able to replace multiplanar 2D-PDwFS. MATERIALS AND METHODS: 52 patients (26 men, mean age: 41.9 +/- 14.5years) underwent magnetic resonance imaging (MRI) of the knee at 3.0 Tesla using a T/R-coil. The imaging protocol included 3 planes of 2D-PDwFS (acquisition time (AT): 6:40 min; voxel sizes: 0.40 - 0.63 * 0.44 - 0.89 * 3mm3) and a 3D-PDwFS (AT: 6:31 min; voxel size: 0.63 * 0.68 * 0.63mm3). Homogeneity of fat suppression (HFS), artifacts, and image sharpness (IS) were evaluated on a 5-point scale (5[excellent] - 1[non-diagnostic]). The sum served as a measure for the overall image quality (OIQ). Contrast ratios (CR) compared to popliteal muscle were calculated for the meniscus (MEN), anterior (ACL) and posterior cruciate ligaments (PCL). In 13 patients who underwent arthroscopic knee surgery, two radiologists evaluated the presence of meniscal, ligamental and cartilage lesions to estimate the sensitivity and specificity of lesion detection. RESULTS: The CR was higher in the ACL, PCL and MEN in 3D- PDwFS compared to 2D-PDwFS (p < 0.01 for ACL and PCL; p = 0.07 for MEN). Compared to 2 D images, the OIQ was rated higher in 3D-PDwFS images (p < 0.01) due to fewer artifacts and HFS despite the lower IS (p < 0.01). The sensitivity and specificity of lesion detection in 3D- and 2D-PDwFS were similar. CONCLUSION: Compared to standard multiplanar 2D-PDwFS knee imaging, isotropic high spatial resolution 3D-PDwFS of the knee at 3.0 T can be acquired with high image quality in a reasonable scan time. Multiplanar reformations in arbitrary planes may serve as an additional benefit of 3D-PDwFS. KEY POINTS: * 3D-PDwFS of the knee is acquired with high image quality* 3D-PDwFS can be achieved in only one measurement with a reasonable scan time* 3D-PDwFS with the advantage of multiplanar reformation may replace 2D-PD-weighted knee MRI Citation Format: * Homsi R, Gieseke J, Luetkens JA et al. Three-Dimensional Isotropic Fat-Suppressed Proton Density-Weighted MRI at 3 Tesla Using a T/R-Coil Can Replace Multiple Plane Two-Dimensional Sequences in Knee Imaging. Fortschr Rontgenstr 2016; 188: 949 - 956. PMID- 27556276 TI - Modern Imaging of Myocarditis: Possibilities and Challenges AB - Myocarditis is known as the chameleon of cardiac diseases. The symptoms and the course of disease vary greatly so that it is often challenging to establish a diagnosis. Early and accurate diagnosis is of utmost importance, since myocarditis is one of the leading causes of sudden cardiac death in young adults and represents an important precursor to dilated cardiomyopathy. Due to the constraints of the routinely used diagnostic approach, including clinical history and examination, laboratory testing, and electrocardiogram, different imaging modalities have emerged over the last decades as contributors to the noninvasive diagnosis of myocarditis. With this interdisciplinary review we would like to present the current state-of-the-art imaging of myocarditis across all available imaging modalities (i. e., echocardiography, cardiac magnetic resonance, cardiac computed tomography, and nuclear medicine). Furthermore, we present novel imaging techniques that might become useful in the near future for easier and more accurate diagnosis of this highly relevant disease. KEY POINTS: * Different imaging modalities are increasingly used in the diagnostic workup of myocarditis.* Several emerging imaging techniques are currently on the way to becoming part of the clinical routine.* This review summarizes the diagnostic value of echocardiography, CMR, CT, and nuclear medicine imaging.* There is special focus on the possibilities and challenges of novel imaging tools within the different modalities. PMID- 27556277 TI - [Not Available]. PMID- 27556278 TI - Continuous Dissolved Oxygen Measurements and Modelling Metabolism in Peatland Streams. AB - Stream water dissolved oxygen was monitored in a 3.2km2 moorland headwater catchment in the Scottish Highlands. The stream consists of three 1st order headwaters and a 2nd order main stem. The stream network is fringed by peat soils with no riparian trees, though dwarf shrubs provide shading in the lower catchment. Dissolved oxygen (DO) is regulated by the balance between atmospheric re-aeration and the metabolic processes of photosynthesis and respiration. DO was continuously measured for >1 year and the data used to calibrate a mass balance model, to estimate primary production, respiration and re-aeration for a 1st order site and in the 2nd order main stem. Results showed that the stream was always heterotrophic at both sites. Sites were most heterotrophic in the summer reflecting higher levels of stream metabolism. The 1st order stream appeared more heterotrophic which was consistent with the evident greater biomass of macrophytes in the 2nd order stream, with resulting higher primary productivity. Comparison between respiration, primary production, re-aeration and potential physical controls revealed only weak relationships. However, the most basic model parameters (e.g. the parameter linking light and photosynthesis) controlling ecosystem processes resulted in significant differences between the sites which seem related to the stream channel geometry. PMID- 27556280 TI - Spin-orbit coupling goes global. PMID- 27556279 TI - A Retrospective Study of G-Tube Use in Japanese Patients Treated with Concurrent Chemoradiotherapy for Hypopharyngeal Cancer. AB - OBJECTIVE: Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7-42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports. METHODS: We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan. RESULTS: At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303). CONCLUSIONS: The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT. PMID- 27556281 TI - Oxygen-Deficient TiO2 - x/Methylene Blue Colloids: Highly Efficient Photoreversible Intelligent Ink. AB - Oxygen-sensitive photoreversible intelligent ink capable of assessment with the human eye is an ongoing demand in the modern era. In the food industry, redox-dye based oxygen indicator films have been proposed, but the leaching of dyes from the film that contaminates the food is one unsolved issue. On the other hand, it is also highly desirable to develop rewritable paper that significantly reduces the pressure on modern society for the production and consumption of paper. Herein, we have developed an oxygen-deficient TiO2 - x/methylene blue (MB) sol without relying on external sacrificial electron donors (SEDs) for photoreversible color switching. Oxygen vacancies in TiO2 - x can work as electron donor to favor the adsorption of the substrate and improve the charge separation that is required for the redox-based color-switching system. The problems of rewriteable paper and food packaging are addressed as two sides of a single coin in this article. We have used hydroxyethyl cellulose (HEC) for rewritable paper that can significantly delay the oxidation of leuco-MB (LMB) through hydrogen bonding and retain the printed information for a long time. The dye leaching from oxygen indicator films is also significantly reduced (only 1.54%) by using furcelleran as the coating polymer that is extracted from edible red seaweed. PMID- 27556282 TI - Enriching acid rock drainage related microbial communities from surface-deposited oil sands tailings. AB - Little is known about the microbial communities native to surface-deposited pyritic oil sands tailings, an environment where acid rock drainage (ARD) could occur. The goal of this study was to enrich sulfur-oxidizing organisms from these tailings and determine whether different populations exist at pH levels 7, 4.5, and 2.5. Using growth-based methods provides model organisms for use in the future to predict potential activities and limitations of these organisms and to develop possible control methods. Thiosulfate-fed enrichment cultures were monitored for approximately 1 year. The results showed that the enrichments at pH 4.5 and 7 were established quicker than at pH 2.5. Different microbial community structures were found among the 3 pH environments. The sulfur-oxidizing microorganisms identified were most closely related to Halothiobacillus neapolitanus, Achromobacter spp., and Curtobacterium spp. While microorganisms related to Chitinophagaceae and Acidocella spp. were identified as the only possible iron-oxidizing and -reducing microbes. These results contribute to the general knowledge of the relatively understudied microbial communities that exist in pyritic oil sands tailings and indicate these communities may have a potential role in ARD generation, which may have implications for future tailings management. PMID- 27556283 TI - Comparative study of strategies for preventing post-ERCP pancreatitis after early precut sphincterotomy for biliary access. AB - OBJECTIVE: Needle knife precut sphincterotomy (PS) during endoscopic retrograde cholangiopancreatography (ERCP) has been associated with a high risk of post-ERCP pancreatitis (PEP). This study aimed to examine the effect of no prophylaxis, somatostatin, rectal diclofenac and pancreatic duct (PD) stenting in reducing rates of PEP in patients who underwent early PS. METHODS: This was a retrospective comparative study and the study period was from January 2006 to December 2015. A standardized approach to early PS was used: (i) inadvertent guidewire cannulation of the PD > thrice; (ii) impacted bile duct stone; (iii) inability to achieve deep cannulation within 10 min. PEP prophylactic measures included: (i) none when there was minimal papilla trauma; (ii) somatostatin infusion; (iii) rectal diclofenac; (iv) PD stent. The difference in rates of PEP between the different strategies was analysed. RESULTS: During the study period, PS was performed in 191 ERCP patients (mean age 66 years; 56.5% males). The ERCP success rate after PS was 93.2% (178/191). Overall the PEP rate was 3.1% (6/191) and the severity in all cases was mild. PEP occurred in 6.1% of patients with PD cannulation but not in those without (P = 0.016). PEP rates were 1.8%, 7.3%, 1.8% and 0% in control, somatostatin, diclofenac and PD stenting groups, respectively (P = 0.209). CONCLUSIONS: There was no significant difference in PEP rates after early PS whether or not prophylactic measures were adopted if there was minimal papilla trauma. A trend towards lower PEP rates was observed in patients who had either rectal diclofenac or PD stenting, compared to somatostatin. PMID- 27556284 TI - Synthesis of Multibranched Gold Nanoechinus Using a Gemini Cationic Surfactant and Its Application for Surface Enhanced Raman Scattering. AB - High-yield multibranched Au nanoechinus possessing lengthy and dense branched nanorods on the surface were synthesized using a seed-mediated surfactant directed approach in the presence of gemini cationic surfactant N,N,N'N' tetramethyl-N,N'-ditetradecylethane-1,2-diaminium bromide (C14C2C14Br2), HAuCl4, AgNO3, and ascorbic acid. C14C2C14Br2 surfactant provides a versatile template in designing the unique morphology of Au nanoechinus with the assistance of AgNO3. UV-vis spectroscopic analysis proves that Au nanoechinus possess a unique intense broad localized surface plasmon resonance (LSPR) peak, which extends from 400 to 1700 nm in the NIR region making a highly potential platform for biomedical applications. Systematic time-dependent TEM, UV-vis-NIR, and XRD analysis were performed to monitor the morphological evolution of multibranched Au nanoechinus. It was found that the surface of branched nanorods of Au NE preferentially grew along (111) crystal planes. Furthermore, as-synthesized Au nanoechinus shows excellent SERS enhancement ability for dopamine inside HeLa cells. PMID- 27556285 TI - The applied statistical approach highly influences the 99th percentile of cardiac troponin I. AB - BACKGROUND: Cardiac troponin (cTn) is the biomarker of choice for assessment of patients with acute coronary syndromes. Guidelines recommend the cTn 99th percentile derived from a cardiovascular healthy reference population as decision threshold. The importance of standardized criteria for the composition of such a reference population is well acknowledged. In this analysis, we investigated to which extent different statistical methods might have bearing on the calculated cTnI 99th percentile. METHODS: cTnI (Abbott) 99th percentiles were determined in 521 cardiovascular healthy community-dwelling subjects using the nonparametric method, the Harrell-Davis bootstrap method and the robust method together with different tests to identify potential outliers (Dixon, Tukey, Reed) and different statistical softwares. RESULTS: The cTnI 99th percentiles (nonparametric method) were 37ng/L (total population), 42ng/L (men) and 25ng/L (women). These estimates differed by -7.4% to +5.7% using the Harrell-Davis bootstrap method and were up to 64.1% lower using the robust method. For the robust method, cTnI 99th percentiles varied by 44.2% depending on the applied software. The method of Tukey classified nine subjects as outliers while no outlier was detected using the other methods. Excluding these nine subjects resulted in up to 60.2% lower cTnI 99th percentiles. CONCLUSIONS: Our results emphasize the need of a standardized statistical approach to calculate cTnI 99th percentiles. Our findings support the use of the nonparametric method and a conservative approach to detect outliers. This requires that the assessed population is sufficiently large and well selected on the basis of stringently applied clinical criteria. PMID- 27556286 TI - Performance of the artus C. difficile QS-RGQ Kit for the detection of toxigenic Clostridium difficile. AB - OBJECTIVES: Nucleic acid amplification tests are commonly used for the direct detection of toxigenic Clostridium difficile. We evaluated the diagnostic performance of newly launched, artus C. difficile QS-RGQ Kit (artus C. difficile, QIAGEN, Hilden, Germany), in comparison with toxigenic culture (TC) and Xpert C. difficile (Cepheid, Sunnyvale, CA, USA). DESIGN AND METHODS: In prospectively collected 261 diarrheal specimens, the artus C. difficile and the Xpert C. difficile assays were performed. TC using chromogenic agar (chromID CD agar, bioMerieux, Marcy-l'Etoile, France) was used a reference method. RESULTS: Based on TC, the sensitivity and specificity of the artus C. difficile were 98.2% and 93.6%, respectively, and those of the Xpert C. difficile were 94.6% and 94.6%, respectively; there was no statistical difference. The agreement between the artus C. difficile and the Xpert C. difficile was almost perfect (kappa=0.918). In the artus C. difficile, the cycle threshold (Ct) values of tcdA were constantly lower than those of tcdB in all positive specimens (mean Ct, 24.5 vs. 26.4; mean difference of 1.9). Three specimens were considered tcdA+/tcdB- by the difference of Ct cutoffs between tcdA and tcdB (38.3 and 36.5, respectively). CONCLUSIONS: The performance of the artus C. difficile is excellent compared with TC and is comparable to that of the Xpert C. difficile. Both PCR assays could be useful diagnostic options for the direct detection of toxigenic C. difficile in clinical laboratories. The optimal Ct cutoff of tcdA and tcdB for artus C. difficile may be further validated in following studies. PMID- 27556287 TI - Fragment-Based Direct-Local-Ring-Coupled-Cluster Doubles Treatment Embedded in the Periodic Hartree-Fock Solution. AB - We present a periodic/finite-cluster interface for fragment-based direct local ring-coupled-cluster doubles (d-LrCCD) calculations embedded in the periodic mean field. The fragment is defined by a set of Wannier functions (WFs), obtained from a periodic Hartree-Fock calculation. The pair-specific virtual space is spanned by projected atomic orbitals (PAOs) truncated to pair domains. The computational procedure is initiated by a periodic local Moller-Plesset (LMP2) calculation. A subset of the WF pairs is then subsequently subjected to a finite-cluster d-LrCCD treatment using the local coupled cluster program of Molpro; this subset is specified by an interorbital cutoff distance. The orbital, pair, and domain lists, as well as other essential quantities needed for d-LrCCD such as the Fock and overlap matrices, and the electron repulsion integrals (ERIs) in the basis of WFs and PAOs are evaluated in the periodic framework and passed to Molpro via an interface. These periodic quantities provide the correct periodic mean-field embedding for the fragment d-LrCCD. Moreover, no expensive orbital transformations involving orbital coefficients related to large supporting clusters are necessary. ERIs appearing in the d-LrCCD diagrams are factorized via density fitting, which enables an efficient processing of the corresponding terms via three-index intermediates. The corresponding 3-index and the metric 2-index ERIs involving auxiliary functions are also computed and transformed to the WF PAO basis (the 3-index ERI) on the periodic side. Although the direct ring-CCD method itself is not generally more accurate than MP2, it is more stable in the case of small band gap systems, as it sums up the ring diagrams to infinite order. Furthermore, this interface is a first step toward a high-level fragment based quantum chemical treatment such as local CCSD(T) within a periodic embedding that is treated at a lower level. As two test examples we study the physisorption of H2 and argon on graphane. PMID- 27556288 TI - Tuning Viral Capsid Nanoparticle Stability with Symmetrical Morphogenesis. AB - Virus-like particles (VLPs) provide engineering platforms for the design and implementation of protein-based nanostructures. These capsids are comprised of protein subunits whose precise arrangement and mutual interactions determine their stability, responsiveness to destabilizing environments, and ability to undergo morphological transitions. The precise interplay between subunit contacts and the overall stability of the bulk capsid population remains poorly resolved. Approaching this relationship requires a combination of techniques capable of accessing nanoscale properties, such as the mechanics of individual capsids, and bulk biochemical procedures capable of interrogating the stability of the VLP ensemble. To establish such connection, a VLP system is required where the subunit interactions can be manipulated in a controlled fashion. The P22 VLP is a promising platform for the design of nanomaterials and understanding how nanomanipulation of the particle affects bulk behavior. By contrasting single particle atomic force microscopy and bulk chemical perturbations, we have related symmetry-specific anisotropic mechanical properties to the bulk ensemble behavior of the VLPs. Our results show that the expulsion of pentons at the vertices of the VLP induces a concomitant chemical and mechanical destabilization of the capsid and implicates the capsid edges as the points of mechanical fracture. Subsequent binding of a decoration protein at these critical edge regions restores both chemical and mechanical stability. The agreement between our single molecule and bulk techniques suggests that the same structural determinants govern both destabilizing and restorative mechanisms, unveiling a phenomenological coupling between the chemical and mechanical behavior of self assembled cages and laying a framework for the analysis and manipulation of other VLPs and symmetric self-assembled structures. PMID- 27556289 TI - Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons. AB - Polyamidoamine (PAMAM) dendrimers are hyperbranched macromolecules which have been described as one of the most promising drug nanocarrier systems. A key process to understand is their cellular internalization mechanism because of its direct influence on their intracellular distribution, association with organelles, entry kinetics, and cargo release. Despite that internalization mechanisms of dendrimers have been studied in different cell types, in the case of neurons they are not completely described. Considering the relevance of central nervous system (CNS) diseases and neuropharmacology, the aim of this report is to describe the molecular internalization mechanism of different PAMAM based dendrimer systems in hippocampal neurons. Four dendrimers based on fourth generation PAMAM with different surface properties were studied: unmodified G4, with a positively charged surface; PP50, with a substitution of the 50% of amino surface groups with polyethylene glycol neutral groups; PAc, with a substitution of the 30% of amino surface groups with acrylate anionic groups; and PFO, decorated with folic acid groups in a 25% of total terminal groups. Confocal images show that both G4 and PFO are able to enter the neurons, but not PP50 and PAc. Colocalization study with specific endocytosis markers and specific endocytosis inhibitor assay demonstrate that clathrin-mediated endocytosis would be the main internalization mechanism for G4, whereas clathrin- and caveolae mediated endocytosis would be implicated in PFO internalization. These results show the existence of different internalization mechanisms for PAMAM dendrimers in neurons and the possibility to control their internalization properties with specific chemical modifications. PMID- 27556290 TI - Advanced Practice Palliative Nursing. PMID- 27556291 TI - The 15-item version of the Boston Naming Test as an index of English proficiency. AB - OBJECTIVE: The present study was designed to examine the potential of the Boston Naming Test - Short Form (BNT-15) to provide an objective estimate of English proficiency. A secondary goal was to examine the effect of limited English proficiency (LEP) on neuropsychological test performance. METHOD: A brief battery of neuropsychological tests was administered to 79 bilingual participants (40.5% male, MAge = 26.9, MEducation = 14.2). The majority (n = 56) were English dominant (EN), and the rest were Arabic dominant (AR). The BNT-15 was further reduced to 10 items that best discriminated between EN and AR (BNT-10). Participants were divided into low, intermediate, and high English proficiency subsamples based on BNT-10 scores (<=6, 7-8, and >=9). Performance across groups was compared on neuropsychological tests with high and low verbal mediation. RESULTS: The BNT-15 and BNT-10 respectively correctly identified 89 and 90% of EN and AR participants. Level of English proficiency had a large effect (partial eta2 = .12-.34; Cohen's d = .67-1.59) on tests with high verbal mediation (animal fluency, sentence comprehension, word reading), but no effect on tests with low verbal mediation (auditory consonant trigrams, clock drawing, digit-symbol substitution). CONCLUSIONS: The BNT-15 and BNT-10 can function as indices of English proficiency and predict the deleterious effect of LEP on neuropsychological tests with high verbal mediation. Interpreting low scores on such measures as evidence of impairment in examinees with LEP would likely overestimate deficits. PMID- 27556293 TI - Options in treating trigeminal neuralgia: Experience with 195 patients. AB - OBJECTIVE: For patients with medically unresponsive trigeminal neuralgia (TN), surgical options include microvascular decompression (MVD), radiofrequency rhizotomy (RF), and stereotactic radiosurgery (SRS). In an attempt to identify the risks and benefits and cost inherent with each of the three modalities, we performed a retrospective review of our experience with 195 cases of TN treated over the past 15 years. METHODS: Since 2001, 195 patients with previously untreated TN were managed: with MVD in 79, RF in 36, and SRS in 80. All patients reported herein underwent preoperative MRI. Women outnumbered men 122/73 (p=0.045). Follow-up after surgery was 32+/-46months. RESULTS: The patients qualifying for MVD were generally healthier and younger, with a mean age+/-SD of 57+/-14, compared to those undergoing RF (75+/-15) or SRS (73+/-13, p<0.0001). In case of relapse, medical treatment was always tried and failed prior to consideration of surgical intervention. A second surgical procedure was necessary in 2, 23, and 18 patients initially treated with MVD, RF, and SRS respectively (p<0.0001). In the patients treated with MVD, RF, and SRS, the average number of procedures per patient necessary to achieve pain control was 1.1, 2.0, and 1.3 respectively (p=0.001). There were 7 complications in the patients treated with MVD but no deaths. Numbness was present in 13, 18, and 29 patients treated with MVD, RF, and SRS respectively (p=0.008). CONCLUSION: MVD for TN is the treatment least likely to fail or require additional treatment. Patients who underwent MVD were younger than those undergoing RF or SRS. The highest rate of recurrence of TN was encountered in patients undergoing RF (64%). Facial numbness was least likely to occur with MVD (16%) compared to RF and SRS (50% and 36% respectively). PMID- 27556292 TI - MoDnm1 Dynamin Mediating Peroxisomal and Mitochondrial Fission in Complex with MoFis1 and MoMdv1 Is Important for Development of Functional Appressorium in Magnaporthe oryzae. AB - Dynamins are large superfamily GTPase proteins that are involved in various cellular processes including budding of transport vesicles, division of organelles, cytokinesis, and pathogen resistance. Here, we characterized several dynamin-related proteins from the rice blast fungus Magnaporthe oryzae and found that MoDnm1 is required for normal functions, including vegetative growth, conidiogenesis, and full pathogenicity. In addition, we found that MoDnm1 co localizes with peroxisomes and mitochondria, which is consistent with the conserved role of dynamin proteins. Importantly, MoDnm1-dependent peroxisomal and mitochondrial fission involves functions of mitochondrial fission protein MoFis1 and WD-40 repeat protein MoMdv1. These two proteins display similar cellular functions and subcellular localizations as MoDnm1, and are also required for full pathogenicity. Further studies showed that MoDnm1, MoFis1 and MoMdv1 are in complex to regulate not only peroxisomal and mitochondrial fission, pexophagy and mitophagy progression, but also appressorium function and host penetration. In summary, our studies provide new insights into how MoDnm1 interacts with its partner proteins to mediate peroxisomal and mitochondrial functions and how such regulatory events may link to differentiation and pathogenicity in the rice blast fungus. PMID- 27556294 TI - Evaluation of pulsing magnetic field effects on paresthesia in multiple sclerosis patients, a randomized, double-blind, parallel-group clinical trial. AB - OBJECTIVES: Evidence is mounting that magnet therapy could alleviate the symptoms of multiple sclerosis (MS). This study was performed to test the effects of the pulsing magnetic fields on the paresthesia in MS patients. PATIENTS AND METHODS: This study has been conducted as a randomized, double-blind, parallel-group clinical trial during the April 2012 to October 2013. The subjects were selected among patients referred to MS clinic of Imam Reza Hospital; affiliated to Kermanshah University of Medical Sciences, Iran. Sixty three patients with MS were included in the study and randomly were divided into two groups, 35 patients were exposed to a magnetic pulsing field of 4mT intensity and 15-Hz frequency sinusoidal wave for 20min per session 2 times per week over a period of 2 months involving 16 sessions and 28 patients was exposed to a magnetically inactive field (placebo) for 20min per session 2 times per week over a period of 2 months involving 16 sessions. The severity of paresthesia was measured by the numerical rating scale (NRS) at 30, 60days. The study primary end point was NRS change between baseline and 60days. The secondary outcome was NRS change between baseline and 30days. RESULTS: Patients exposing to magnetic field showed significant paresthesia improvement compared with the group of patients exposing to placebo. CONCLUSION: According to our results pulsed magnetic therapy could alleviate paresthesia in MS patients .But trials with more patients and longer duration are mandatory to describe long-term effects. PMID- 27556295 TI - Intelligent biology and medicine in 2015: advancing interdisciplinary education, collaboration, and data science. AB - We summarize the 2015 International Conference on Intelligent Biology and Medicine (ICIBM 2015) and the editorial report of the supplement to BMC Genomics. The supplement includes 20 research articles selected from the manuscripts submitted to ICIBM 2015. The conference was held on November 13-15, 2015 at Indianapolis, Indiana, USA. It included eight scientific sessions, three tutorials, four keynote presentations, three highlight talks, and a poster session that covered current research in bioinformatics, systems biology, computational biology, biotechnologies, and computational medicine. PMID- 27556296 TI - Dysregulation of the BRCA1/long non-coding RNA NEAT1 signaling axis contributes to breast tumorigenesis. AB - Dysregulation of long non-codng RNA (lncRNA) expression has been found to contribute to tumorigenesis. However, the roles of lncRNAs in BRCA1-related breast cancer remain largely unknown. In this study, we delineate the role of the novel BRCA1/lncRNA NEAT1 signaling axis in breast tumorigenesis. BRCA1 inhibits NEAT1 expression potentially through binding to its genomic binding site upstream of the NEAT1 gene. BRCA1 deficiency in human normal/cancerous breast cells and mouse mammary glands leads to NEAT1 overexpression. Our studies show that NEAT1 upregulation resulting from BRCA1 deficiency stimulates in vitro and in vivo breast tumorigenicity. We have further identified molecular mediators downstream of the BRCA1/NEAT1 axis. NEAT1 epigenetically silences miR-129-5p expression by promoting the DNA methylation of the CpG island in the miR-129 gene. Silencing of miR-129-5p expression by NEAT1 results in upregulation of WNT4 expression, a target of miR-129-5p, which leads to activation of oncogenic WNT signaling. Our functional studies indicate that this NEAT1/miR-129-5p/WNT4 axis contributes to the tumorigenic effects of BRCA1 deficiency. Finally our in silico expression correlation analysis suggests the existence of the BRCA1/NEAT1/miR-129-5p axis in breast cancer. Our findings, taken together, suggest that the dysregulation of the BRCA1/NEAT1/miR-129-5p/WNT4 signaling axis is involved in promoting breast tumorigenesis. PMID- 27556297 TI - Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma. AB - In the present work, we show that T-cell lymphoblastic lymphoma cells exhibit a reduction of FADD availability in the cytoplasm, which may contribute to impaired apoptosis. In addition, we observe a reduction of FADD phosphorylation that inversely correlates with the proliferation capacity and tumor aggressiveness. The resultant balance between FADD-dependent apoptotic and non-apoptotic abilities may define the outcome of the tumor. Thus, we propose that FADD expression and phosphorylation can be reliable biomarkers with prognostic value for T-LBL stratification. PMID- 27556298 TI - Ligand-activated PPARgamma downregulates CXCR4 gene expression through a novel identified PPAR response element and inhibits breast cancer progression. AB - Stromal Derived Factor-1alpha (SDF-1alpha) and its cognate receptor CXCR4 play a key role in mediating breast cancer cell invasion and metastasis. Therefore, drugs able to inhibit CXCR4 activation may add critical tools to reduce tumor progression, especially in the most aggressive form of the breast cancer disease. Peroxisome Proliferator-Activated Receptor (PPAR) gamma, a member of the nuclear receptor superfamily, has been found to downregulate CXCR4 gene expression in different cancer cells, however the molecular mechanism underlying this effect is not fully understood. Here, we identified a novel PPARgamma-mediated mechanism that negatively regulates CXCR4 expression in both epithelial and stromal breast cancer cells. We found that ligand-activated PPARgamma downregulated CXCR4 transcriptional activity through the recruitment of the silencing mediator of retinoid and thyroid hormone receptor (SMRT) corepressor onto a newly identified PPAR response element (PPRE) within the CXCR4 promoter in breast cancer cell lines. As a consequence, the PPARgamma agonist rosiglitazone (BRL) significantly inhibited cell migration and invasion and this effect was PPARgamma-mediated, since it was reversed in the presence of the PPARgamma antagonist GW9662. According to the ability of cancer-associated fibroblasts (CAFs), the most abundant component of breast cancer stroma, to secrete high levels of SDF-1alpha, BRL reduced migratory promoting activities induced by conditioned media (CM) derived from CAFs and affected CXCR4 downstream signaling pathways activated by CAF-CM. In addition, CAFs exposed to BRL showed a decreased expression of CXCR4, a reduced motility and invasion along with a phenotype characterized by an altered morphology. Collectively, our findings provide novel insights into the role of PPARgamma in inhibiting breast cancer progression and further highlight the utility of PPARgamma ligands for future therapies aimed at targeting both cancer and surrounding stromal cells in breast cancer patients. PMID- 27556299 TI - Body mass index as a prognostic factor in patients with extranodal natural killer/T-cell lymphoma, nasal type. AB - Epidemiological evidence has shown that body mass index (BMI) can predict survival in several types of cancer. However, the role of BMI in extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is still unclear. This retrospective single-center study included 251 newly diagnosed patients to determine the prognostic value of BMI in ENKTL. Of these, 203 patients received chemoradiotherapy, 37 received chemotherapy alone, 8 received radiotherapy alone, and 3 received only best supportive care. With a median follow-up of 28 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) rates were 64.4% and 60.9%, respectively. The receiver-operating characteristic curve showed that 20.8 kg/m2 was the optimal cut-off of BMI to predict survival. BMI < 20.8 kg/m2 was associated with lower 3-year OS (52.8% vs. 72.9%, P = 0.001) and PFS (48.8% vs. 69.8%, P < 0.001) rates. Multivariate analysis indicated that BMI, performance status, lactate dehydrogenase (LDH) levels, chemotherapy, and radiotherapy were independent prognostic factors for OS. Furthermore, BMI, number of extranodal sites, performance status, LDH, and radiotherapy were predictive of PFS. These results suggest that BMI at the cut-off of 20.8 kg/m2 might be a prognostic factor in patients with ENKTL. PMID- 27556300 TI - Adjuvant radiation therapy in stage I seminoma: 20 years of oncologic results. AB - AIM: To report long term oncologic outcomes after adjuvant radiotherapy (RT) for stage I seminoma. METHOD: We reviewed the complete data set for all patients treated at our institute between 1988 and 2005 for stage I seminoma with adjuvant RT after radical orchiectomy . RESULTS: A total of 85 patients were included. The median follow-up was 15 years. The 20-year overall survival (OS) and relapse free survival (RFS) were 92% and 96.3%, respectively. No severe acute and late complications were recorded. Overall 5.9% of patients had a second unrelated malignancy. CONCLUSION: Adjuvant RT is an efficacious and safe treatment in stage I seminoma. PMID- 27556301 TI - Diagnosis and treatment pattern among rural and urban breast cancer patients in Southwest China from 2005 to 2009. AB - The incidence of all cancers in China is generally higher in urban areas; however, the mortality risk for affected patients is considerably higher in rural areas. We present a subanalysis investigating the differences in patient and disease characteristics, treatment patterns, and outcomes between rural and urban patients who were diagnosed with breast cancer at West China Hospital between 2005-2009. Baseline patient and disease characteristics were recorded, and patients were followed up for a minimum of 3 years, or until death. For this subanalysis, patients were stratified by their residential status (rural or urban). Of the 2252 patients in the cohort, 76.3% were from urban areas and 22.1% were from rural areas. Significant differences were observed in the prevalence of luminal A and human epidermal growth factor receptor 2-positive breast cancers among rural and urban patients. Estrogen receptor (ER)-positive patients were less likely to receive anti-ER therapy if they were from rural areas compared with urban areas; the use of aromatase inhibitors was also significantly lower for rural patients than urban patients. Univariate, multivariate, and Kaplan Meier analyses all demonstrated that overall survival and progression-free survival were significantly lower for rural patients than urban patients. PMID- 27556303 TI - Role of Jnk1 in development of neural precursors revealed by iPSC modeling. AB - Jnk1-deficient mice manifest disrupted anterior commissure formation and loss of axonal and dendritic microtubule integrity. However, the mechanisms and the specific stages underlying the developmental defects remain to be elucidated. Here, we report the generation of Jnk1-deficient (Jnk1 KO) iPSCs from Jnk1 KO mouse tail-tip fibroblasts (TTFs) for modeling the neural disease development. The efficiency in the early induction of iPSCs was higher from Jnk1 KO fibroblasts than that of wild-type (WT) fibroblasts. These Jnk1 KO iPSCs exhibited pluripotent stem cell properties and had the ability of differentiation into general three embryonic germ layers in vitro and in vivo. However, Jnk1 KO iPSCs showed reduced capacity in neural differentiation in the spontaneous differentiation by embryoid body (EB) formation. Notably, by directed lineage differentiation, Jnk1 KO iPSCs specifically exhibited an impaired ability to differentiate into early stage neural precursors. Furthermore, the neuroepitheliums generated from Jnk1 KO iPSCs appeared smaller, indicative of neural stem cell developmental defects, as demonstrated by teratoma tests in vivo. These data suggest that Jnk1 dei!?ciency inhibits the development of neural stem cells/precursors and provide insights to further understanding the complex pathogenic mechanisms of JNK1-related neural diseases. PMID- 27556302 TI - Protein arginine methylation/demethylation and cancer. AB - Protein arginine methylation is a common post-translational modification involved in numerous cellular processes including transcription, DNA repair, mRNA splicing and signal transduction. Currently, there are nine known members of the protein arginine methyltransferase (PRMT) family, but only one arginine demethylase has been identified, namely the Jumonji domain-containing 6 (JMJD6). Although its demethylase activity was initially challenged, its dual activity as an arginine demethylase and a lysine hydroxylase is now recognized. Interestingly, a growing number of substrates for arginine methylation and demethylation play key roles in tumorigenesis. Though alterations in the sequence of these enzymes have not been identified in cancer, their overexpression is associated with various cancers, suggesting that they could constitute targets for therapeutic strategies. In this review, we present the recent knowledge of the involvement of PRMTs and JMJD6 in tumorigenesis. PMID- 27556304 TI - Not all 1p/19q non-codeleted oligodendroglial tumors are astrocytic. AB - Although 1p/19q codeletion is the genetic hallmark defining oligodendrogliomas, approximately 30-40% of oligodendroglial tumors have intact 1p/19q in the literature and they demonstrate a worse prognosis. This group of 1p/19q intact oligodendroglial tumors is frequently suggested to be astrocytic in nature with TP53 and ATRX mutations but actually remains under-investigated. In the present study, we provided evidence that not all 1p/19q intact oligodendroglial tumors are astrocytic through histologic and molecular approaches. We examined 1p/19q status by FISH in a large cohort of 337 oligodendroglial tumors and identified 39.8% lacking 1p/19q codeletion which was independently associated with poor prognosis. Among this 1p/19q intact oligodendroglial tumor cohort, 58 cases demonstrated classic oligodendroglial histology which showed older patient age, better prognosis, association with grade III histology, PDGFRA expression, TERTp mutation, as well as frequent IDH mutation. More than half of the 1p/19q intact oligodendroglial tumors showed lack of astrocytic defining markers, p53 expression and ATRX loss. TP53 mutational analysis was additionally conducted in 45 cases of the 1p/19q intact oligodendroglial tumors. Wild-type TP53 was detected in 71.1% of cases which was associated with classic oligodendroglial histology. Importantly, IDH and TERTp co-occurred in 75% of 1p/19q intact, TP53 wild-type oligodendrogliomas, highlighting the potential of the co-mutations in assisting diagnosis of oligodendrogliomas in tumors with clear cell morphology and non-codeleted 1p/19q status. In summary, our study demonstrated that not all 1p/19q intact oligodendroglial tumors are astrocytic and co-evaluation of IDH and TERTp mutation could potentially serve as an adjunct for diagnosing 1p/19q intact oligodendrogliomas. PMID- 27556305 TI - Molecular dissection of the valproic acid effects on glioma cells. AB - Many glioblastoma patients suffer from seizures why they are treated with antiepileptic agents. Valproic acid (VPA) is a histone deacetylase inhibitor that apart from its anticonvulsive effects in some retrospective studies has been suggested to lead to a superior outcome of glioblastoma patients. However, the exact molecular effects of VPA treatment on glioblastoma cells have not yet been deciphered. We treated glioblastoma cells with VPA, recorded the functional effects of this treatment and performed a global and unbiased next generation sequencing study on the chromatin (ChIP) and RNA level. 1) VPA treatment clearly sensitized glioma cells to temozolomide: A protruding VPA-induced molecular feature in this context was the transcriptional upregulation/reexpression of numerous solute carrier (SLC) transporters that was also reflected by euchromatinization on the histone level and a reexpression of SLC transporters in human biopsy samples after VPA treatment. DNA repair genes were adversely reduced. 2) VPA treatment, however, also reduced cell proliferation in temozolomide-naive cells: On the molecular level in this context we observed a transcriptional upregulation/reexpression and euchromatinization of several glioblastoma relevant tumor suppressor genes and a reduction of stemness markers, while transcriptional subtype classification (mesenchymal/proneural) remained unaltered. Taken together, these findings argue for both temozolomide-dependent and -independent effects of VPA. VPA might increase the uptake of temozolomide and simultaneously lead to a less malignant glioblastoma phenotype. From a mere molecular perspective these findings might indicate a surplus value of VPA in glioblastoma therapy and could therefore contribute an additional ratio for clinical decision making. PMID- 27556306 TI - Associated Clinical and Laboratory Markers of Donor on Allograft Function After Heart Transplant. AB - INTRODUCTION: Primary graft dysfunction is a major cause of mortality after heart transplantation. OBJECTIVE: To evaluate correlations between donor-related clinical/biochemical markers and the occurrence of primary graft dysfunction/clinical outcomes of recipients within 30 days of transplant. METHODS: The prospective study involved 43 donor/recipient pairs. Data collected from donors included demographic and echocardiographic information, noradrenaline administration rates and concentrations of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2), interleukins (IL-6 and IL-10), monocyte chemoattractant protein-1, C-reactive protein and cardiac troponin I. Data collected from recipients included operating, cardiopulmonary bypass, intensive care unit and hospitalization times, inotrope administration and left/right ventricular function through echocardiography. RESULTS: Recipients who developed moderate/severe left ventricular dysfunction had received organs from significantly older donors (P =0.020). Recipients from donors who required moderate/high doses of noradrenaline (>0.23 ug/kg/min) around harvesting time exhibited lower post-transplant ventricular ejection fractions (P =0.002) and required longer CPB times (P =0.039). Significantly higher concentrations of sTNFR1 (P =0.014) and sTNFR2 (P =0.030) in donors were associated with reduced intensive care unit times (<=5 days) in recipients, while higher donor IL-6 (P =0.029) and IL-10 (P =0.037) levels were correlated with reduced hospitalization times (<=25 days) in recipients. Recipients who required moderate/high levels of noradrenaline for weaning off cardiopulmonary bypass were associated with lower donor concentrations of sTNFR2 (P =0.028) and IL-6 (P =0.001). CONCLUSION: High levels of sTNFR1, sTNFR2, IL-6 and IL-10 in donors were associated with enhanced evolution in recipients. Allografts from older donors, or from those treated with noradrenaline doses >0.23 ug/kg/min, were more frequently affected by primary graft dysfunction within 30 days of surgery. PMID- 27556307 TI - Institutional Impact of EVAR's Incorporation in the Treatment of Abdominal Aortic Aneurysm: a 12 Years' Experience Analysis. AB - INTRODUCTION: Endovascular aneurysm repair (EVAR) was introduced as a less aggressive treatment of abdominal aortic aneurysms (AAA) for patients ineligible for open repair (OR). OBJECTIVE: To analyze EVAR's incorporation impact in the treatment of infra-renal abdominal aortic aneurysms in our institution. METHODS: A retrospective study of the patients with diagnostic of infra-renal AAA treated between December 2001 and December 2013 was performed. The choice between EVAR and OR was based on surgeon's experience, considering patient clinical risk and aneurysm's anatomical features. Patients treated by EVAR and by OR were analyzed. In each group, patient's and aneurysm's characteristics, surgical and anesthesia times, cost, transfusion rate, intraoperative complications, hospital stay, mortality and re-intervention rates and survival curves were evaluated. RESULTS: The mean age, all forms of heart disease and chronic renal failure were more common in EVAR group. Blood transfusion, surgical and anesthesia times and mean hospital stay were higher for OR. Intraoperative complications rate was higher for endovascular aneurysm repair, overall during hospitalization complication rate was higher for open repair. The average cost in endovascular aneurysm repair was 1448.3? higher. Re-interventions rates within 30 days and late re intervention were 4.1% and 11.7% for endovascular aneurysm repair versus 13.7% and 10.6% for open repair. CONCLUSIONS: Two different groups were treated by two different techniques. The individualized treatment choice allows to achieve a mortality of 2.7%. Age >=80 years influences survival curve in OR group and ASA >=IV in EVAR group. We believe EVAR's incorporation improved the results of OR itself. Patients with more comorbidities were treated by endovascular aneurysm repair, decreasing those excluded from treatment. Late reinterventions were similar for both techniques. PMID- 27556308 TI - Clopidogrel use After Myocardial Revascularization: Prevalence, Predictors, and One-Year Survival Rate. AB - INTRODUCTION: Antiplatelet therapy after coronary artery bypass graft (CABG) has been used. Little is known about the predictors and efficacy of clopidogrel in this scenario. OBJECTIVE: Identify predictors of clopidogrel following CABG. METHODS: We evaluated 5404 patients who underwent CABG between 2000 and 2009 at Duke University Medical Center. We excluded patients undergoing concomitant valve surgery, those who had postoperative bleeding or death before discharge. Postoperative clopidogrel was left to the discretion of the attending physician. Adjusted risk for 1-year mortality was compared between patients receiving and not receiving clopidogrel during hospitalization after undergoing CABG. RESULTS: At hospital discharge, 931 (17.2%) patients were receiving clopidogrel. Comparing patients not receiving clopidogrel at discharge, users had more comorbidities, including hyperlipidemia, hypertension, heart failure, peripheral arterial disease and cerebrovascular disease. Patients who received aspirin during hospitalization were less likely to receive clopidogrel at discharge (P<=0.0001). Clopidogrel was associated with similar 1-year mortality compared with those who did not use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however, an interaction between the use of cardiopulmonary bypass and clopidogrel, with lower 1-year mortality in patients undergoing off-pump CABG who received clopidogrel, but not those undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032). CONCLUSION: Clopidogrel was used in nearly one-fifth of patients after CABG. Its use was not associated with lower mortality after 1 year in general, but lower mortality rate in those undergoing off-pump CABG. Randomized clinical trials are needed to determine the benefit of routine use of clopidogrel in CABG. PMID- 27556309 TI - Dacron Graft Intussusception Technique for Treatment of Type A Aortic Dissections: Technical Notes and Preliminary Results. AB - INTRODUCTION: Optimal surgical management for acute type A aortic dissection (AAAD) remains unclear. The in-hospital mortality rate is still high (15%), and the intraoperative bleeding is an independent risk factor for hospital mortality. OBJECTIVE: The aim of our study was describe a new method for aortic anastomosis in the repair of AAAD and report the hospital mortality and bleeding complications. METHODS: Between January 2008 and November 2014, 24 patients, 16 male, median age 62 years, underwent surgical treatment of AAAD. The surgical technique consisted of intussusception of a Dacron tube in the dissected aorta, which is anastomosed with a first line of 2-0 polyester everting mattress suture and a second line of 3-0 polypropylene running suture placed at the outermost side. Open distal anastomosis was performed with bilateral selective antegrade cerebral perfusion in 13 (54.1%) patients. RESULTS: Cardiopulmonary bypass and aortic clamping time ranged from 75 to 135 min (mean=85 min) and 60 to 100 min (mean=67 min), respectively. The systemic circulatory arrest ranged from 29 to 60 min (mean=44.5 min). One (4.1%) patient required reoperation for bleeding, due to the use of preoperative clopidogrel. The postoperative bleeding was 382-1270 ml (mean=654 ml). We used an average of 4.2 units of red blood cells/patient. There were two (8.3%) hospital deaths, one due to intraoperative bleeding and another due to mesenteric ischemia. The average length of stay in the intensive care unit and hospital was 44 hours and 6.7 days, respectively. CONCLUSION: This new method for surgical correction of AAAD was reproducible and resulted in satisfactory clinical outcomes. PMID- 27556310 TI - Effect of LIMA Harvesting Technique on Postoperative Drainage in Off-Pump CABG. AB - OBJECTIVE: We investigated the effects of pedicled and semiskeletonized left internal mammary artery (LIMA) harvesting techniques on postoperative drainage in patients subjected to off-pump CABG, ignoring other advantages or disadvantages of those techniques. METHODS: The present study comprises a total of 160 subjects that underwent coronary artery bypass surgery in our clinic. Data were collected consecutively and retrospectively. An attempt was made to have similar groups in terms of demographic characteristics. Patients that underwent off-pump coronary artery bypass surgery by two surgical teams which differed only in LIMA harvesting technique were dichotomized and compared according to these techniques. The first group (Group 1) consisted of patients in whom LIMA was harvested with surrounding tissues using the pedicled technique. The second group (Group 2) consisted of patients in whom LIMA was harvested using the semiskeletonized technique, with the veins separated from surrounding connective tissues. RESULTS: The mean amount of drainage in the first 24 hours was 706.1+/ 234.2 ml vs. 591+/-258.8 ml (Group 1 vs. Group 2; P=0.005), the mean amount of drainage in the second 24 hours was 270+/-133.6 ml vs. 189.4+/-140.4 ml (Group 1 vs. Group 2; P<0.001), and the mean amount of total drainage was determined to be 976.1+/-306.9 ml vs. 781.2+/-335.5 ml (Group 1 vs. Group 2; P<0.001). CONCLUSION: It was observed that semiskeletonized LIMA presents reduced amount of postoperative drainage in the first and second 24-hour periods and total amount of drainage than pedicled LIMA, independent of pleural integrity. PMID- 27556311 TI - Endovascular Treatment of Internal Iliac Artery Aneurysms: Single Center Experience. AB - OBJECTIVE: Internal iliac artery aneurysms (IIAA) are rare, representing only 0.3% of aortoiliac aneurysms. Its treatment with open surgery is complex and associated with high morbidity and mortality, which led to increasing application of endovascular solutions. In this study, we aimed to evaluate outcomes of endovascular aneurysm repair (EVAR) of IIAA in one institution. METHODS: We retrospectively reviewed all cases of IIAA treated with endovascular techniques between 2003 and 2014. Endpoints were morbidity, mortality, freedom from pelvic ischemic symptoms (buttock claudication, ischemic colitis, and spinal cord injury), and need for reintervention. RESULTS: There were 16 patients, 13 males and 3 females, with mean age of 75.1+/-7 years. A total of 20 IIAA (4 cases were bilateral), with mean diameter of 37.9 mm, were treated. EVAR was performed in 13 (81.3%) patients, with associated internal iliac artery's outflow occlusion in 2. Iliac branch device was used in one patient. Two patients underwent endovascular IIAA embolization alone. One patient underwent percutaneous, transgluteal, IIAA embolization. IIAA flow preservation in at least one internal iliac artery was possible in 9 (56.3%) patients. Early mortality was 7% (1 case). Early morbidity was 18.8%. Pelvic ischemic complications occurred in 1 (7%) patient with buttock claudication. Late reintervention was needed in 3 patients, none of them for IIAA related complications. CONCLUSION: Endovascular treatment of IIAA is technically feasible and durable. Although overall morbidity is relatively high, major complications are infrequent and perioperative mortality is low. internal iliac artery flow preservation is technically challenging and, in a significant number of cases, not possible at all. PMID- 27556312 TI - Is Age a Determinant Factor in EVAR as a Predictor of Outcomes or in the Selection Procedure? Our Experience. AB - INTRODUCTION: Endovascular aneurysm repair (EVAR) is the therapy of choice in high risk patients with abdominal aortic aneurysm. The good results described are leading to the broadening of clinical indications to younger patients. However, reintervention rates seem higher and even with successful treatment sometimes there is growth of the aneurysm sac and rupture, meaning a failure of the therapeutic goal. This study proposes to analyse the impact of age in patients' selection and post-EVAR results. METHODS: The clinical records of consecutive patients undergoing endovascular aneurysm repair, between 2001 and 2013, were retrospectively reviewed. Patients were divided according to age groups (<70, 70 80 and >80 years). Gender, body mass index, aneurysm anatomic features, neck characteristics, iliac morphology, surgical indication, endograft type, anesthesic risk classification, length of stay, reinterventions and mortality were analysed and compared. RESULTS: The study included 171 patients, 161 (94.1%) men, and mean age 74.1+/-8.9 years. The age group under 70 had 32% of the patients. Only three characteristics were found different among age groups: 1) body mass index was higher in younger patients, with a considerable trend toward significance (P=0.06); 2) surgical indication, in the younger group, surgeon's and the patient's option were more proeminent (P<0.05); 3) erectile dysfunction was higher in elderly group (P<0.05). No other clinical and anatomical characteristics or final outcomes were found statisticaly different among age groups. CONCLUSION: The absence of statistically differences in mortality and reinterventions among age groups suggests that age by itself is not a relevant factor in endovascular aneurysm repair. Indeed, the three characteristics different in younger (obesity, sexual function and patient's choice) favor endovascular aneurysm repair. PMID- 27556313 TI - Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery. AB - INTRODUCTION: Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. OBJECTIVE: To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. METHODS: This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. RESULTS: 50 patients, 27 (54%) males were included, with a mean age of 56.7+/-13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5+/-14.9 vs. 83.1+/-19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4+/-102.8 vs. 502.4+/-112.8 m, P=0.0031). CONCLUSION: We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery. PMID- 27556314 TI - Dilatation of Common Iliac Arteries after Endovascular Infrarenal Abdominal Aortic Repair with Bell-Bottom Extension. AB - OBJECTIVE: Endovascular techniques to treat abdominal aortic aneurysms results in lower morbidity and mortality rates. However, dilation of the common iliac arteries prevents adequate distal sealing, which compromises the procedure success. The aim of this study is report the long-term outcomes of patients with abdominal aortic aneurysms associated with aneurysm of the common iliac artery following endovascular repair using a bifurcated bell-bottom stent graft. METHODS: This is a retrospective study that evaluated patients treated with bifurcated bell-bottom extension stent grafts to repair an infrarenal abdominal aortic aneurysm and who had at least one common iliac artery with dilatation >= 1.5 cm for at least 12 months after the endovascular intervention. RESULTS: Thirty-eight patients with a mean age of 70.4+/-8.2 years were included. Stent graft placement was followed by dilation of the common iliac artery aneurysms in 35.3% of cases; endoleak and reoperation rates were 17.6% and 15.7%, respectively. Younger patients showed a higher rate of artery diameter increase following the procedure. The average arterial dilation was 16% in the first year, 29% in the second year, 57% in the third year and 95% from the fourth year until the end of follow-up. CONCLUSION: Repair of infrarenal abdominal aortic aneurysms with bifurcated bell-bottom type stents when there is common iliac artery dilation is a good therapeutic option to preserve hypogastric flow. The rate of endoleak was 17.6%, and 15.7% of cases required reoperation. Younger patients are more likely to experience dilation of the common iliac artery after the procedure. PMID- 27556315 TI - Experimental Validation of a Cardiac Simulator for in vitro Evaluation of Prosthetic Heart Valves. AB - OBJECTIVE: This work describes the experimental validation of a cardiac simulator for three heart rates (60, 80 and 100 beats per minute), under physiological conditions, as a suitable environment for prosthetic heart valves testing in the mitral or aortic position. METHODS: In the experiment, an aortic bileaflet mechanical valve and a mitral bioprosthesis were employed in the left ventricular model. A test fluid of 47.6% by volume of glycerin solution in water at 36.5oC was used as blood analogue fluid. A supervisory control and data acquisition system implemented previously in LabVIEW was applied to induce the ventricular operation and to acquire the ventricular signals. The parameters of the left ventricular model operation were based on in vivo and in vitro data. The waves of ventricular and systemic pressures, aortic flow, stroke volume, among others, were acquired while manual adjustments in the arterial impedance model were also established. RESULTS: The acquired waves showed good results concerning some in vivo data and requirements from the ISO 5840 standard. CONCLUSION: The experimental validation was performed, allowing, in future studies, characterizing the hydrodynamic performance of prosthetic heart valves. PMID- 27556316 TI - Mitral Valve Prolapse in Pregnancy. AB - Mitral valve prolapse is a benign condition. Mitral regurgitation is only complicated in patients with severe mitral valve prolapse. Women with mitral valve prolapse in the absence of other cardiovascular disorders tolerate pregnancy well and do not develop remarkable cardiac complications. Nevertheless, serious complications of mitral valve prolapse, including arrhythmia, infective endocarditis and cerebral ischemic events, can be present in pregnancy. Debates remain with regard to the use of prophylactic antibiotics and beta-blockers in the pregnant women with mitral valve prolapse. The prognosis of the pregnant patients might be closely related to the pathological and (or) functional changes of the mitral valve. Non-myxomatous mitral valve prolapse poses no or little obstetric risks in terms of pregnancy, labor and neonatal complications; whereas myxomatous mitral valve prolapse is a major etiology of valvular heart disease in women of childbearing age. In the pregnant patients with mitral valve prolapse progressing into major complications, surgical interventions are considered. Medicinal treatment of such patients with beta-blockers should be a concern for the fetal safety. PMID- 27556317 TI - The Middle Ages Contributions to Cardiovascular Medicine. AB - The historical period called the Middle Ages, a long interval between the 5th and the 15th centuries, is still commonly known as the Dark Ages, especially in the area of health sciences. In the last decades, this "classic" view of the Middle Ages has been gradually modified with advances in historiographical studies and the history of science. During that period in Western Europe, knowledge about the human body suffered a regression in terms of anatomy and physiology, with the predominance of religious conceptions mainly about diseases and their treatments. Knowledge on the cardiovascular system and heart diseases has been classically described as a repetition of the concepts developed by Galen from the dissection of animals and his keen sense of observation. However, the Middle East, especially Persia, was the birth place of a lot of intellectuals who preserved the ancient knowledge of the Greeks while building new knowledge and practices, especially from the 8th to the 13th century. The invasion of the Arabs in North of Africa and the Iberian Peninsula and the eclosion of the Crusades resulted in a greater contact between the East and the West, which in turn brought on the arrival of the Arab medical knowledge, among others, to 12th century Europe. Such fact contributed to an extremely important change in the scientific medical knowledge in the West, leading to the incorporation of different concepts and practices in the field of cardiovascular Medicine. The new way of teaching and practicing Medicine of the great Arab doctors, together with the teaching hospitals and foundations in the Koran, transformed the Medicine practiced in Europe definitely. The objective of this paper is to describe the knowledge drawn up from the Middle Ages about the cardiovascular system, its understanding and therapeutic approach to cardiologists and cardiovascular surgeons. PMID- 27556318 TI - Duration of Systole and Diastole for Hydrodynamic Testing of Prosthetic Heart Valves: Comparison Between ISO 5840 Standards and in vivo Studies. AB - OBJECTIVE: To complement the ISO 5840 standards concerning the duration of left ventricular systole and diastole as a function of changes in heart rates according to in vivo studies from the physiologic literature review. METHODS: The systolic and diastolic durations from three in vivo studies were compared with the durations of systole proposed by the ISO 5840:2010 and ISO 5840-2:2015 for hydrodynamic performance assessment of prosthetic heart valves. RESULTS: Based on the in vivo studies analyzed, the systolic durations proposed by the ISO 5840 standard seemed consistent for 45 and 120 beats per minute (bpm), and showed diverse results for the 70 bpm condition. CONCLUSION: Information on the realistic validation of the operation of left ventricular models for different heart rates were obtained. PMID- 27556319 TI - Major Intrahepatic Veno-Venous Fistula after Fontan Operation Treated by Transcatheter Implantation of Amplatzer Septal Occluder through Internal Jugular Vein. AB - Six months after undergoing a Fontan operation, a 7-year-old boy with right atrial isomerism and a single functional ventricle was admitted to our emergency department with cyanosis. Emergency cardiac catheterization revealed a large veno venous fistula that began in a left hepatic vein, connected to the left accessory hepatic veins, and drained into the common atrium, resulting in desaturation. The fistula was occluded proximally with an Amplatzer septal occluder, with satisfying results; the patient's systemic arterial saturation decreased during his hospital stay. Three weeks after the first intervention, a second procedure was performed to retrieve the first device and to close the fistula distally. Multiple attempts with different types of gooseneck snares and a bioptome catheter failed to retrieve the first device, so a telescopic method was used to re-screw it. Using a Mullins long sheath and delivery sheath, the delivery cable was manipulated to fit into the slot of the end screw, and the cable was rotated gently in a clockwise direction to re-screw the device. Then, another Amplatzer septal occluder was placed at the distal end of the fistula. In conclusion, distal transcatheter occlusion of intrahepatic veno-venous fistulas might lead to better clinical outcomes in selected patients. Amplatzer septal occluder device can be retrieve without any complication within three weeks. PMID- 27556320 TI - Bispectral Index Monitoring in Patients Undergoing Open Heart Surgery. AB - INTRODUCTION: To obtain the optimal anesthesia depth is not easy in cardiovascular surgery patients where the haemodynamic reserve is limited, due to reasons such as not being able to give the desired dose of anesthetic agent, or the change in the pharmacokinetics of the agent in the heart-lung machine. This study was planned to assess the contribution of bispectral index (BIS) monitoring in the depth of anesthesia. METHODS: The patients were divided into 2 groups, and BIS monitoring was used for each patient. Group 1 (G1 n=35): keeping the BIS monitor screen open, the anesthesia need was set. Group 2 (G2 n=35): BIS monitor was tied to the patient and the monitor screen was closed in such a way that the anaesthesist couldn't see the BIS value. When the recording time came, the data on the monitor was recorded. The need for the anesthetic agent was set according to the parameters such as haemodynamics or follow up of pupils, instead of BIS value, by titrating the anesthetic infusion doses. RESULTS: BIS values were similar in both groups before the induction, BIS values in both groups showed a decrease, showing no significant statistical difference (P>0.05). One patient in each group said that he dreamt, and one patient in G2 said that he had heard a noise and felt that he was taken from one place to another. CONCLUSION: The management should be done with clinical evaluation, haemodynamics and other monitorization methods and BIS monitoring findings together. PMID- 27556321 TI - Initial Surgical Experience with Aortic Valve Repair: Clinical and Echocardiographic Results. AB - INTRODUCTION: Due to late complications associated with the use of conventional prosthetic heart valves, several centers have advocated aortic valve repair and/or valve sparing aortic root replacement for patients with aortic valve insufficiency, in order to enhance late survival and minimize adverse postoperative events. METHODS: From March/2012 thru March 2015, 37 patients consecutively underwent conservative operations of the aortic valve and/or aortic root. Mean age was 48+/-16 years and 81% were males. The aortic valve was bicuspid in 54% and tricuspid in the remaining. All were operated with the aid of intraoperative transesophageal echocardiography. Surgical techniques consisted of replacing the aortic root with a Dacron graft whenever it was dilated or aneurysmatic, using either the remodeling or the reimplantation technique, besides correcting leaflet prolapse when present. Patients were sequentially evaluated with clinical and echocardiographic studies and mean follow-up time was 16+/-5 months. RESULTS: Thirty-day mortality was 2.7%. In addition there were two late deaths, with late survival being 85% (CI 95% - 68%-95%) at two years. Two patients were reoperated due to primary structural valve failure. Freedom from reoperation or from primary structural valve failure was 90% (CI 95% - 66%-97%) and 91% (CI 95% - 69%-97%) at 2 years, respectively. During clinical follow-up up to 3 years, there were no cases of thromboembolism, hemorrhage or endocarditis. CONCLUSIONS: Although this represents an initial series, these data demonstrates that aortic valve repair and/or valve sparing aortic root surgery can be performed with satisfactory immediate and short-term results. PMID- 27556322 TI - Profile of Heart Donors from the Human Valve Bank of the Santa Casa de Misericordia de Curitiba. AB - INTRODUCTION: Human heart valves are used as replacement valves and have satisfactory functional results compared with conventional prostheses. OBJECTIVE: Characterize the profile of effective heart donors from the human valve bank of the santa casa de misericordia de curitiba and analyze the association between the profile variables. METHODS: It consists of a retrospective and quantitative study of electronic medical records from heart donors for heart valves. every heart donation made to the bank between january 2004 and december 2014 was studied. RESULTS: 2,149 donations were analyzed, from donors aged 0 to 71 years old, with an average of 34.9 +/- 15.03 years old. most donors were male 65.7% (n=1,411) and 34.3% (n=738) were female. among the most frequent causes of the donors' death are trauma at 53% (n=1,139) and cerebral vascular accident at 34.2% (n=735). there was significant statistical association between the analyzed variables. CONCLUSION: There has been an improvement in brazil's donation rate, being essential that the tissue banks work together with the state and federal district centers for notification, procurement and distribution of organs in order to increase the number of donors. PMID- 27556323 TI - Off-Pump Triple Coronary Artery Bypass Grafting in a Patient with Situs Inversus Totalis: Case Presentation and a Brief Review of the Brazilian and the International Experiences. AB - A 76-year-old man with situs inversus totalis underwent a successful off-pump three-vessel coronary artery bypass surgery. The postoperative course was uneventful, and the patient was discharged 8 days later. At 9-month follow-up a coronary computed tomography angiography confirmed the viability of all of the grafts, and one year after the operation the patient remained asymptomatic. It comprises the fifth Brazilian case of a coronary surgery in a patient with situs inversus totalis and the first one of the country of a coronary artery bypass surgery without the use of the cardiopulmonary bypass in this condition. PMID- 27556325 TI - It is Time to Renew! PMID- 27556324 TI - Dysfunctional Hyperpolarization-Activated Cyclic Nucleotide-gated Ion Channels in Cardiac Diseases. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP) or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions. PMID- 27556326 TI - Brazilian Registry of Cardiovascular Surgery in Adults Fully Operational. PMID- 27556327 TI - The Role of Age in the Abdominal Aortic Aneurysm Repair. PMID- 27556328 TI - Morphological and histochemical characterization of the digestive tract of the puffer fish Sphoeroides testudineus (Linnaeus 1758) (Tetraodontiformes: Tetraodontidae). AB - Morphological analysis of the digestive tract of Sphoeroides testudineus showed an esophagus with an anterior and a posterior portion, the abdominal pouch. No stomach was observed between the abdominal pouch and the intestine. The intestine was arranged in three segments and two loops, and the distal portion had the rectum opening into the anus. Histochemical analyses showed that the esophagus secreted acid mucosecretions, and that there was a qualitative increase in goblet cells from the proximal to distal area of the intestine. The rectum showed cells secreting acid and neutral mucus. Given these features, this species presents a morphology which creates a link between its ecology and behavior. PMID- 27556329 TI - Lipolytic response of adipose tissue and metabolic adaptations to long periods of fasting in red tilapia (Oreochromis sp., Teleostei: Cichlidae). AB - Adaptive changes of carbohydrate and lipid metabolism induced by 7, 15, 30, 60, 90, 150 and 200 days of fasting were investigated in red tilapia (Oreochromis sp.). Plasma glucose, lactate and free fatty acids (FFA) levels, liver and muscle glycogen and total lipid contents and rates of FFA release from mesenteric adipose tissue (MAT) were measured. Plasma glucose levels showed significant differences only after 90 days of fasting, when glycemia was 34% lower (50+/ 5mg.dL-1) than fed fish values (74+/-1mg.dL-1), remaining relatively constant until 200 days of fasting. The content of liver glycogen ("15%) in fed tilapia fell 40% in 7 days of food deprivation. In 60, 90 and 150 days of fasting, plasma FFA levels increased 49%, 64% and 90%, respectively, compared to fed fish values. In agreement with the increase in plasma FFA, fasting induced a clear increase in lipolytic activity of MAT incubated in vitro. Addition of isobutylmethylxanthine (cAMP-phosphodiesterase inhibitor) and isoproterenol (non selective beta adrenergic agonist) to the incubation medium induced a reduction of lipolysis in fasted fish, differently to what was observed in mammal adipose tissue. This study allowed a physiological assessment of red tilapia response to starvation. PMID- 27556330 TI - rDNA mapping, heterochromatin characterization and AT/GC content of Agapanthus africanus (L.) Hoffmanns (Agapanthaceae). AB - Agapanthus (Agapanthaceae) has 10 species described. However, most taxonomists differ respect to this number because the great phenotypic plasticity of the species. The cytogenetic has been an important tool to aid the plant taxon identification, and to date, all taxa of Agapanthus L'Heritier studied cytologically, presented 2n = 30. Although the species possess large chromosomes, the group is karyologically little explored. This work aimed to increase the cytogenetic knowledge of Agapanthus africanus (L.) Hoffmanns by utilization of chromosome banding techniques with DAPI / CMA3 and Fluorescent in situ Hybridization (FISH). In addition, flow cytometry was used for determination of DNA content and the percentage of AT / GC nitrogenous bases. Plants studied showed 2n = 30 chromosomes, ranging from 4.34 - 8.55 um, with the karyotype formulae (KF) = 10m + 5sm. Through FISH, one 45S rDNA signal was observed proximally to centromere of the chromosome 7, while for 5S rDNA sites we observed one signal proximally to centromere of chromosome 9. The 2C DNA content estimated for the species was 2C = 24.4 with 59% of AT and 41% of GC. Our data allowed important upgrade for biology and cytotaxonomy of Agapanthus africanus (L.) Hoffmanns. PMID- 27556331 TI - Bioprospecting of lipolytic microorganisms obtained from industrial effluents. AB - The lipases have ability to catalyze diverse reactions and are important in different biotechnological applications. The aim of this work was to isolate and characterize microorganisms that produce lipases, from different food industry effluents localized in Pelotas, RS/Brazil. Bacteria were identified using Gram stain and biochemical tests (Vitek 2(r)). Fungi were identified according to macro and micromorphology characteristics. The extracellular lipase production was evaluated using the Rhodamine B test and the enzymatic activity by titration. Twenty-one bacteria were isolated and identified as Klebsiella pneumoniae ssp. pneumoniae, Serratia marcescens, Enterobacter aerogenes, Raoultella ornithinolytica and Raoultella planticola. Were characterized isolated filamentous fungi by the following genera: Alternaria sp., Fusarium sp., Geotrichum sp., Gliocladium sp., Mucor sp., Paecilomyces sp. and Trichoderma sp. Extracellular lipase production was observed in 71.43% of the bacteria and 57.14% of the fungi. The bacterium that presented better promising enzymatic activity was E. aerogenes (1.54 U/ml) however between fungi there was not significant difference between the four isolates. This study indicated that microorganisms lipase producers are present in the industrial effluents, as well as these enzymes have potential of biodegradation of lipid compounds. PMID- 27556332 TI - Biological functions of selenium and its potential influence on Parkinson's disease. AB - Parkinson's disease is characterized by the death of dopaminergic neurons, mainly in the substantia nigra, and causes serious locomotor dysfunctions. It is likely that the oxidative damage to cellular biomolecules is among the leading causes of neurodegeneration that occurs in the disease. Selenium is an essential mineral for proper functioning of the brain, and mainly due to its antioxidant activity, it is possible to exert a special role in the prevention and in the nutritional management of Parkinson's disease. Currently, few researchers have investigated the effects of selenium on Parkinson's disease. However, it is known that very high or very low body levels of selenium can (possibly) contribute to the pathogenesis of Parkinson's disease, because this imbalance results in increased levels of oxidative stress. Therefore, the aim of this work is to review and discuss studies that have addressed these topics and to finally associate the information obtained from them so that these data and associations serve as input to new research. PMID- 27556333 TI - Phaeosphaeria deschampsii (Ascomycota): A new parasite species of Deschampsia antarctica (Poaceae) described to Antarctica. AB - This study presents the description of Phaeosphaeria deschampsii, which was found in plant communities from Half Moon Island, South Shetland Archipelago, Antarctica, in February 2014. Many patches of Deschampsia antarctica (Poaceae), the only indigenous Poaceae specie in Antarctic, were found dead, parasitized by a fungi pathogen. Based on the shape of its perithecia, with oblique neck, erumpent in the grass tissues, ascospore form and septation, the specie was identified as new to science. PMID- 27556334 TI - Luigi Naldini on His Lifelong Involvement with the Development of Gene Therapy. PMID- 27556335 TI - Influence of IV Contrast Administration on CT Measures of Muscle and Bone Attenuation: Implications for Sarcopenia and Osteoporosis Evaluation. AB - OBJECTIVE: The objective of our study was to characterize enhancement of muscle and bone that occurs on standardized four-phase contrast-enhanced CT. MATERIALS AND METHODS: Two musculoskeletal radiologists reviewed standardized four-phase abdominal CT scans obtained with IV contrast material. The psoas area was measured, and the mean attenuation (in Hounsfield units) was recorded for the aorta, psoas muscles, posterior paraspinal muscles, and L4 vertebral body. CT attenuation measures were compared between anatomic regions and imaging phases with the paired t test; associations between measures were examined with the Pearson correlation coefficient (R). RESULTS: The study included 201 patients (97 men, 104 women; mean age, 57.7 +/- 12.5 [SD] years). Subject age was inversely correlated with unenhanced attenuation in the psoas muscles, posterior paraspinal muscles, and L4 (p < 0.001). The psoas muscles, posterior paraspinal muscles, and L4 enhanced significantly (p < 0.001) at all three contrast-enhanced phases. The greatest muscle enhancement was observed on delayed phase scans, whereas the greatest enhancement in L4 was seen on portal phase imaging. The unenhanced attenuation of the psoas muscles was significantly and negatively correlated with enhancement of the psoas muscles at the portal and delayed phases (p < 0.05 and p < 0.01, respectively), but these correlations were not seen for the posterior paraspinal muscles. Age was positively correlated with posterior paraspinal muscle enhancement at the portal and delayed phases in men (p < 0.05 and p < 0.01, respectively) but not in women. CONCLUSION: Contrast enhancement of commonly measured muscle and bone regions is routinely observed and should be considered when using CT attenuation values as biomarkers of sarcopenia and osteoporosis. Furthermore, CT enhancement may be significantly influenced by age, sex, and unenhanced tissue attenuation. PMID- 27556337 TI - The Impact of Maturity Stage on Cell Membrane Integrity and Enzymatic Browning Reactions in High Pressure Processed Peaches (Prunus persica). AB - Fruit maturity is an important factor associated with final product quality, and it may have an effect on the level of browning in peaches that are high pressure processed (HPP). Peaches from three different maturities, as determined by firmness (M1 = 50-55 N, M2 = 35-40 N, and M3 = 15-20 N), were subjected to pressure levels at 0.1, 200, and 400 MPa for 10 min. The damage from HPP treatment results in loss of fruit integrity and the development of browning during storage. Increasing pressure levels of HPP treatment resulted in greater damage, particularly in the more mature peaches, as determined by shifts in transverse relaxation time (T2) of the vacuolar component and by light microscopy. The discoloration of peach slices of different maturities processed at the same pressure was comparable, indicating that the effect of pressure level is greater than that of maturity in the development of browning. PMID- 27556338 TI - Following Metabolism in Living Microorganisms by Hyperpolarized (1)H NMR. AB - Dissolution dynamic nuclear polarization (dDNP) is used to enhance the sensitivity of nuclear magnetic resonance (NMR), enabling monitoring of metabolism and specific enzymatic reactions in vivo. dDNP involves rapid sample dissolution and transfer to a spectrometer/scanner for subsequent signal detection. So far, most biologically oriented dDNP studies have relied on hyperpolarizing long-lived nuclear spin species such as (13)C in small molecules. While advantages could also arise from observing hyperpolarized (1)H, short relaxation times limit the utility of prepolarizing this sensitive but fast relaxing nucleus. Recently, it has been reported that (1)H NMR peaks in solution phase experiments could be hyperpolarized by spontaneous magnetization transfers from bound (13)C nuclei following dDNP. This work demonstrates the potential of this sensitivity-enhancing approach to probe the enzymatic process that could not be suitably resolved by (13)C dDNP MR. Here we measured, in microorganisms, the action of pyruvate decarboxylase (PDC) and pyruvate formate lyase (PFL)-enzymes that catalyze the decarboxylation of pyruvate to form acetaldehyde and formate, respectively. While (13)C NMR did not possess the resolution to distinguish the starting pyruvate precursor from the carbonyl resonances in the resulting products, these processes could be monitored by (1)H NMR at 500 MHz. These observations were possible in both yeast and bacteria in minute-long kinetic measurements where the hyperpolarized (13)C enhanced, via (13)C -> (1)H cross relaxation, the signals of protons binding to the (13)C over the course of enzymatic reactions. In addition to these spontaneous heteronuclear enhancement experiments, single-shot acquisitions based on J-driven (13)C -> (1)H polarization transfers were also carried out. These resulted in higher signal enhancements of the (1)H resonances but were not suitable for multishot kinetic studies. The potential of these (1)H-based approaches for measurements in vivo is briefly discussed. PMID- 27556339 TI - A Study of 2-Iodobutane by Rotational Spectroscopy. AB - Rotational transitions belonging to 2-iodobutane (sec-butyl-iodide, CH3CHICH2CH3) were measured over the frequency range 5.5-16.5 GHz via jet-pulsed Fourier transform microwave spectroscopy. The complete nuclear quadrupole coupling tensor of iodine, chi, was obtained for the gauche (g)-, anti (a)-, and gauche' (g') conformers as well as the four (13)C isotopologues of the gauche species. Rotational constants, centrifugal distortion constants, quadrupole coupling constants, and nuclear spin-rotation constants were determined for each species. Changes in chi of the iodine nucleus, resulting from conformational and isotopic differences, are discussed. Isotopic substitution of g-2-iodobutane allowed for an rs structure to be determined for the carbon backbone. Additionally, isotopic substitution in conjunction with an ab initio structure allowed for a fit of various r0 structural parameters belonging to g-2-iodobutane. PMID- 27556336 TI - Systems Biology and Clinical Practice in Respiratory Medicine. The Twain Shall Meet. AB - Respiratory diseases are highly complex, being driven by host-environment interactions and manifested by inflammatory, structural, and functional abnormalities that vary over time. Traditional reductionist approaches have contributed vastly to our knowledge of biological systems in health and disease to date; however, they are insufficient to provide an understanding of the behavior of the system as a whole. In this Pulmonary Perspective, we discuss systems biology approaches, especially but not limited to the study of the lung as a complex system. Such integrative approaches take into account the large number of dynamic subunits and their interactions found in biological systems. Borrowing methods from physics and mathematics, it is possible to study the collective behavior of these systems over time and in a multidimensional manner. We first examine the physiological basis for complexity in the respiratory system and its implications for disease. We then expand on the potential applications of systems biology methods to study complex systems, within the context of diagnosis and monitoring of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and critical illness. We summarize the significant advances made in recent years using systems approaches for disease phenotyping, applied to data ranging from the molecular to clinical level, obtained from large scale asthma and COPD networks. We describe new studies using temporal complexity patterns to characterize asthma and COPD and predict exacerbations as well as predict adverse outcomes in critical care. We highlight new methods that are emerging with this approach and discuss remaining questions that merit greater attention in the field. PMID- 27556340 TI - Highly Flexible Self-Powered Organolead Trihalide Perovskite Photodetectors with Gold Nanowire Networks as Transparent Electrodes. AB - Organolead trihalide perovskites (OTPs) such as CH3NH3PbI3 (MAPbI3) have attracted much attention as the absorbing layer in solar cells and photodetectors (PDs). Flexible OTP devices have also been developed. Transparent electrodes (TEs) with higher conductivity, stability, and flexibility are necessary to improve the performance and flexibility of flexible OTP devices. In this work, patterned Au nanowire (AuNW) networks with high conductivity and stability are prepared and used as TEs in self-powered flexible MAPbI3 PDs. These flexible PDs show peak external quantum efficiency and responsivity of 60% and 321 mA/W, which are comparable to those of MAPbI3 PDs based on ITO TEs. The linear dynamic range and response time of the AuNW-based flexible PDs reach ~84 dB and ~4 MUs, respectively. Moreover, they show higher flexibility than ITO-based devices, around 90%, and 60% of the initial photocurrent can be retained for the AuNW based flexible PDs when bent to radii of 2.5 and 1.5 mm. This work suggests a high-performance, highly flexible, and stable TE for OTP flexible devices. PMID- 27556341 TI - Erratum. PMID- 27556342 TI - Optimisation of one-step desolvation and scale-up of gelatine nanoparticle production. AB - Gelatine nanoparticles (GNPs) are biodegradable and biocompatible drug delivery systems with excellent clinical performances. A two-step desolvation is commonly used for their preparation, although this methodology has several shortcomings: lack of reproducibility, small scales and low yields. A straightforward and more consistent GNP preparation approach is presented here focusing on the development of a one-step desolvation with the use of a commercially available gelatine type. Controlled stirring conditions and ultrafiltration are used to achieve large scale production of nanoparticles of up to 2.6 g per batch. Particle size distributions are conserved and comparable to those determined for two-step desolvation on small scale. Additionally, a range of cross-linking agents is examined for their effectiveness in stabilising GNPs as an alternative to glutaraldehyde. Glyceraldehyde demonstrated outstanding properties, which led to high colloidal stability. This approach optimises the manufacturing process and the scale-up of the production capacity, providing a clear potential for future applications. PMID- 27556343 TI - Progressive Proptosis Secondary to an Orbital Floor Implant. AB - A 49-year-old female with advanced left maxillary squamous cell carcinoma underwent total maxillectomy. The orbital floor was reconstructed using a titanium mesh implant and the midface reformed with a free fibula flap. Following reconstruction, the patient developed progressive left-sided proptosis. Review of postoperative imaging prompted extraction of the titanium implant, rapidly normalizing globe position. This unique case highlights the clinical relevance of orbital venous anatomy. PMID- 27556344 TI - Cicatricial Eyelid Paralysis Secondary to Trigeminal Trophic Syndrome. PMID- 27556345 TI - Necrotizing Fasciitis of the Periorbital Region Complicated by Combined Central Retinal Artery Occlusion, Central Retinal Vein Occlusion, and Posterior Ciliary Occlusion. AB - A 50 year-old man on immunosuppressive agents presented with left eye vision loss, periorbital swelling, pain, and ophthalmoplegia. The patient was clinically found to have a central retinal artery and vein occlusion. A CT scan was performed which demonstrated intraorbital fat stranding, however the patient lacked sinus disease. The etiology of the orbital infection was held in question. The area was debrided in the operating room, and the specimen demonstrated group A streptococcal species consistent with necrotizing fasciitis. Periorbital necrotizing fasciitis should be suspected in patients with rapidly progressive orbital symptoms without sinus disease as lack of surgical intervention can result in poor outcomes. The unusual aspect to this case is the mechanism of vision loss, as the authors hypothesize that there was vascular infiltration of the infection resulting in the central retinal artery occlusion and central retinal vein occlusion which have not been previously reported secondary to necrotizing fasciitis of the orbit. PMID- 27556346 TI - Predictive Factors for Intermittent Self-catheterization in German and Brazilian Individuals With Spina Bifida and Neurogenic Bladder Dysfunction. AB - PURPOSE: Our study aimed to identify predictive factors for the use of intermittent self-catheterization (ISC) in persons with spina bifida (SB) and neurogenic bladder. Cultural effects were evaluated by comparing ISC use in individuals from 2 countries, Germany and Brazil. DESIGN: Cross-sectional, descriptive study. SUBJECTS AND SETTING: The study included 71 Brazilian and 77 German individuals with SB (108 females and 92 males), aged between 6 and 55 years, who have used ISC for bladder management. METHODS: Data were collected using printed (Brazil) and online (Germany) questionnaires, with 53 questions related to intermittent catheterization (IC) technique, the materials used in IC, difficulties with IC, and sociodemographic and health variables. Data were analyzed using analysis of variance and multivariate logistical regression. RESULTS: Self-catheterization and assisted catheterization were used for 92 and 56 patients, respectively. Intermittent self-catheterization was more common in German participants (79.2%), while most Brazilian participants used assisted catheterization (56.3%). The following variables influenced the choice of catheterization method, according to logistic regression: age, education level, presence of hydrocephalus, severity of SB, and nationality. The variables unrelated to ISC use included gender, difficulty obtaining ISC equipment or learning to perform ISC, and wheelchair dependency. CONCLUSIONS: The identification of predictive factors for ISC improved our understanding of ISC in SB patients and should aid in the development of more effective strategies to increase ISC use. PMID- 27556347 TI - Measuring Weight-Bearing Activities in Patients With Previous Diabetic Foot Ulcers. AB - PURPOSE: The purpose of this article was to evaluate the accuracy of 2 physical activity monitors, monitors 1 and 2, for measuring weight-bearing activity in persons with prior diabetic foot ulcers. DESIGN: Cross-sectional design. INSTRUMENTS: Two recently developed monitors were used to differentiate anatomical postures such as lying, sitting, and standing upright. One monitor was designed to distinguish between duration of standing and walking and the other combines duration of standing and walking into 1 measure. SUBJECTS AND SETTING: Thirty-one subjects were recruited; all participants had experienced a diabetic foot ulcer and completed participation in a previous cohort study. The study setting was 2 medical centers in the Midwestern United States. METHODS: Subjects simultaneously wore the 2 monitors while performing 14 weight-bearing (ie, walking and standing) and non-weight-bearing (ie, sitting and lying) activities. The duration spent on each activity and the total number of steps taken for each walking activity were directly observed and recorded with each monitor. The accuracy of monitors 1 and 2 was assessed via direct observation as a reference standard. Paired-samples t tests were used to examine the difference in accuracy between the 2 monitors. RESULTS: For measuring duration of activity, the accuracy of monitor 1 ranged from 73% to 100% for walking, 50% for standing, and from 42% to 100% for sitting/lying. In contrast, the accuracy of monitor 2 ranged from 98% to 100% for walking, 100% for standing, and from 97% to 100% for sitting/lying. The accuracy of monitor 1 for counting the number of steps ranged from 43% to 81%, while the accuracy of monitor 2 ranged from 91% to 99%. Monitor 2 was significantly more accurate than monitor 1 in measuring duration of standing still, slow walking, pedaling while sitting, lying on the left, and lying on the right, as well as measuring steps across different kinds of walking activities. Differences in monitor accuracy between subjects with and without foot pain and between subjects with and without foot amputation were not statistically significant. CONCLUSION: These findings suggest that monitor 2 is a more accurate measure of weight-bearing activities than monitor 1 among patients with previous diabetic foot ulcers. Additionally, the 2 monitors differ in terms of function; monitor 2 distinguishes standing from walking, whereas monitor 1 combines standing and walking into 1 measure. We recommend monitor 2 to examine the impact of weight-bearing activity on foot ulceration in patients with diabetic neuropathy. PMID- 27556348 TI - Efficacy and safety of intracoronary verapamil versus sodium nitroprusside for the prevention of microvascular obstruction during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. AB - OBJECTIVE: The aim of this study was to compare the role of intracoronary (IC) verapamil versus sodium nitroprusside (SNP) in the prevention of microvascular obstruction (MVO) during a primary percutaneous coronary intervention (pPCI). BACKGROUND: A head-to-head comparison between verapamil and SNP in the prevention of MVO lacks evidence. PATIENTS AND METHODS: Sixty patients with ST-segment elevation myocardial infarction were randomized to receive IC verapamil (n=30) versus SNP (n=30) during pPCI. The primary outcome was the incidence of angiographic MVO as defined by Thrombolysis In Myocardial Infarction flow less than 3 or Thrombolysis In Myocardial Infarction flow 3 with myocardial blush grade less than 2. The secondary outcomes were the percentage of ST-segment resolution on 12-lead ECG, left ventricular ejection fraction and wall motion score index by two-dimensional echocardiography at 3-5 days after pPCI, as well as major adverse cardiovascular events at 30 days. Safety outcomes were the incidence of hypotension and/or bradycardia during pPCI. RESULTS: Verapamil was associated with lower incidence of angiographic MVO compared with SNP (13.3 vs. 40%, respectively; P=0.02), as well as superior ST-segment resolution greater than or equal to 70% (33.3 vs. 6.7%, respectively; P=0.01). There was a trend towards improved left ventricular ejection fraction with verapamil (42.6+/-4.9 vs. 40.4+/-4.7%, respectively; P=0.09), but with similar wall motion score index (1.43+/-0.1 vs. 1.45+/-0.2, respectively; P=0.14). Both groups had similar 30-day major adverse cardiovascular events (3.3 vs. 6.7%, respectively; P=0.55). Verapamil was associated with lower incidence of hypotension compared with SNP (3.3 vs. 20%, respectively; P=0.04). CONCLUSION: In pPCI, IC verapamil results in significant improvements in MVO with a better safety profile compared with SNP. Larger trials should be conducted to confirm these results. PMID- 27556349 TI - Stereotactic body radiotherapy for oligoprogressive cancer. AB - Stereotactic body radiotherapy (SBRT) is a focused tumour treatment that produces high local control rates with low toxicity. Its use in metastatic cancer is evolving rapidly, with purported benefits in the oligometastatic setting and for better palliation of symptomatic disease. Another potential indication for SBRT is in the setting of oligoprogression, where there is progression of a solitary or a few tumours while all other tumours are responding or stable on a systemic therapy strategy. SBRT to the progressing "rogue" tumours may delay the need to start or change systemic therapy. This may have clinical benefits including improved progression-free/overall survival and quality of life for patients. This review will summarize the limited published data. More prospective clinical trials are urgently needed to better identify and quantify the potential clinical benefits. PMID- 27556350 TI - Developing the First Recombinant Factor XIII for Congenital Factor XIII Deficiency: Clinical Challenges and Successes. AB - Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing plasma derived products containing FXIII (fresh frozen plasma, cryoprecipitate, and plasma-derived FXIII concentrates), all of which contain both subunits. Despite the increased safety of plasma-derived products, concern remains regarding potential viral safety issues. This review describes the development, from concept to clinical use, of a recombinant FXIII molecule (containing subunit A only; rFXIII-A2) for congenital FXIII-A subunit deficiency. Unmet needs and ongoing challenges in congenital FXIII deficiency are also discussed. Despite the challenges in developing a product for a very rare bleeding disorder, the information gathered on efficacy, safety, and pharmacokinetics of FXIII replacement therapy represents the largest dataset on congenital FXIII-A subunit deficiency in the world. It also provides evidence for the safety and efficacy of monthly prophylaxis with 35 IU/kg of rFXIII-A2 in patients with FXIII-A subunit deficiency. The issues encountered and overcome, along with lessons learned, may be applied to and encourage the development of new recombinant products for other rare bleeding disorders. PMID- 27556351 TI - The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. AB - Extracellular matrix (ECM) deposition during wound healing is a physiological response to an insult. Wound healing becomes deregulated in the setting of chronic injury or long-standing metabolic disease, leading to the accumulation of ECM components and fibrosis. Matrix protein turnover is determined by the rate of synthesis as well as the rate of proteolytic degradation and clearance by matrix metalloproteinases (MMPs). The persistent activation of interstitial myofibroblasts, coupled with defects in matrix proteolysis, ultimately disrupts tissue architecture and leads to biochemical and mechanical organ dysfunction with eventual organ failure. Plasminogen activator inhibitor type-1 (PAI-1) regulates tissue homeostasis and wound healing by inhibiting plasmin-mediated MMP activation. Multiple reports using models of liver, lung, and kidney fibrosis suggest that PAI-1 deficiency or inhibition of PAI-1 activity attenuates fibrosis. The disinhibition of plasmin-mediated MMP activation leads to collagen degradation and its diminished accumulation, resulting in the reduction of fibrotic matrix deposition in these organs. Paradoxically, homozygous deficiency of PAI-1 promotes age-dependent spontaneous cardiac fibrosis, suggesting a protective role for PAI-1 in the heart. It remains unclear whether PAI-1 deficient cardiac fibroblasts have increased proliferative, migratory, or differentiation capabilities, that allow them to overcome increased plasmin and MMP activity and matrix clearance. In this review, we examine the specific roles of PAI-1 in fibrosis of different organs including the lung, liver, kidney, and cardiovascular system. PMID- 27556352 TI - Differences in Radiation Dose Response between Small and Large Intestinal Crypts. AB - The protection of intestinal epithelial cells from the lethal effects induced by high-dose radiation is an important issue in radiotherapy and in the treatment of acute radiation syndrome. However, the effects of middle- and low-dose radiation on intestinal epithelial cells remain unclear. Because the accumulation of DNA damage in intestinal stem cells may be crucial for the development of cancer initiating cells, it is important to understand the kinetics of DNA repair and tissue response (which are involved in the elimination of damaged cells and tissue injury repair) to middle- to low-dose irradiation. In this study, mice were X-ray irradiated with 0.1, 1 or 4 Gy, after which the small intestine (duodenum and ileum) and colon were harvested from the animals. DNA damage repair and the elimination of damaged cells were quantified by measuring the number of foci of 53BP1, a surrogate marker for DNA double-strand breaks. Tissue proliferative response was evaluated by determining the number of Ki-67(+) and mitotic cells. Intra-crypt response differed considerably between the small intestine and the colon. In the small intestine, 53BP1 foci were detected immediately after irradiation, but rapidly disappeared thereafter, especially noticeable in Lgr5(+) stem cells. Cellular growth was temporally arrested; however, cell numbers and mitotic cell numbers in the crypt did not change. The kinetics of DNA damage repair in Lgr5(+) stem cells were similar to those in the small intestines, while the colon was more susceptible to radiation-induced damage. Preferential cell loss in the lower crypt was clearly observed in the colon; and after low-dose X-ray irradiation, only the colon exhibited considerably reduced cell numbers and dramatic induction of mitosis. These results suggest that differences in radiation dose response between the small and the large intestine may depend on the growth activity of stem cells after DNA repair. PMID- 27556354 TI - Chirality-Discriminated Conductivity of Metal-Amino Acid Biocoordination Polymer Nanowires. AB - Biocoordination polymer (BCP) nanowires are successfully constructed through self assembly of chiral cysteine amino acids and Cd cations in solution. The varied chirality of cysteine is explored to demonstrate the difference of BCP nanowires in both morphology and structure. More interestingly and surprisingly, the electrical property measurement reveals that, although all Cd(II)/cysteine BCP nanowires behave as semiconductors, the conductivity of the Cd(II)/dl-cysteine nanowires is 4 times higher than that of the Cd(II)/l-cysteine or Cd(II)/d cysteine ones. The origin of such chirality-discriminated characteristics registered in BCP nanowires is further elucidated by theoretical calculation. These findings demonstrate that the morphology, structure, and property of BCP nanostructures could be tuned by the chirality of the bridging ligands, which will shed light on the comprehension of chirality transcription as well as construction of chirality-regulated functional materials. PMID- 27556353 TI - Transcript Analysis for Internal Biodosimetry Using Peripheral Blood from Neuroblastoma Patients Treated with (131)I-mIBG, a Targeted Radionuclide. AB - Calculating internal dose from therapeutic radionuclides currently relies on estimates made from multiple radiation exposure measurements, converted to absorbed dose in specific organs using the Medical Internal Radiation Dose (MIRD) schema. As an alternative biodosimetric approach, we utilized gene expression analysis of whole blood from patients receiving targeted radiotherapy. Collected blood from patients with relapsed or refractory neuroblastoma who received (131)I labeled metaiodobenzylguanidine ((131)I-mIBG) at the University of California San Francisco (UCSF) was used to compare calculated internal dose with the modulation of chosen gene expression. A total of 40 patients, median age 9 years, had blood drawn at baseline, 72 and 96 h after (131)I-mIBG infusion. Whole-body absorbed dose was calculated for each patient based on the cumulated activity determined from injected mIBG activity and patient-specific time-activity curves combined with (131)I whole-body S factors. We then assessed transcripts that were the most significant for describing the mixed therapeutic treatments over time using real time polymerase chain reaction (RT-PCR). Modulation was evaluated statistically using multiple regression analysis for data at 0, 72 and 96 h. A total of 10 genes were analyzed across 40 patients: CDKN1A; FDXR; GADD45A; BCLXL; STAT5B; BAX; BCL2; DDB2; XPC; and MDM2. Six genes were significantly modulated upon exposure to (131)I-mIBG at 72 h, as well as at 96 h. Four genes varied significantly with absorbed dose when controlling for time. A gene expression biodosimetry model was developed to predict absorbed dose based on modulation of gene transcripts within whole blood. Three transcripts explained over 98% of the variance in the modulation of gene expression over the 96 h (CDKN1A, BAX and DDB2). To our knowledge, this is a novel study, which uses whole blood collected from patients treated with a radiopharmaceutical, to characterize biomarkers that may be useful for biodosimetry. Our data indicate that transcripts, which have been previously identified as biomarkers of external exposures in ex vivo whole blood and in vivo radiotherapy patients, are also good early indicators of internal exposure. However, for internal sources of radiation, the biokinetics and physical decay of the radionuclide strongly influence the gene expression. PMID- 27556355 TI - CD151-mediated adhesion is crucial to osteosarcoma pulmonary metastasis. AB - CD151, a tetraspanin family protein involved in cell-cell and cell-extracellular matrix interaction, is differentially expressed in osteosarcoma cell membranes. Thus, this study aimed to investigate the role of CD151 in osteosarcoma metastasis. We analyzed CD151 expression in patient tissue samples using immunohistochemistry. CD151 expression was also silenced with shRNA in osteosarcoma cells of high metastatic potential, and cell adhesion, migration and invasion were evaluated in vitro and pulmonary metastasis was investigated in vivo. Mediators of cell signaling pathways were also examined following suppression of CD151 expression. Overall survival for patients with low versus high CD151 expression level was 94 vs. 41 months (p=0.0451). CD151 expression in osteosarcoma cells with high metastatic potential was significantly higher than in those with low metastatic potential (p<0.001). shRNA-mediated silencing of CD151 did not influence cell viability or proliferation; however, cell adhesion, migration and invasion were all inhibited (all p<0.001). In mice inoculated with shRNA-transduced osteosarcoma cells, the number and size of lung metastatic lesions were reduced compared to the mice inoculated with control-shRNA transduced cells (p<0.001). In addition, CD151 knockdown significantly reduced Akt, p38, and p65 phosphorylation as well as focal adhesion kinase, integrin beta1, p70s6, and p-mTOR levels. Taken together, CD151 induced osteosarcoma metastasis likely by regulating cell function through adhesion signaling. Further studies are necessary to fully explore the diagnostic and prognostic value of determining CD151 expression in osteosarcoma patients. PMID- 27556357 TI - Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer. AB - Prostate cancer (PCa) is a leading cause of mortality among males. Long non coding RNAs (lncRNAs) are subclass of noncoding RNAs that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE. Combined the two results, a total of 44 androgen-responsive lncRNAs with ARE were found to be over-expressed in PCa samples. Ten lncRNAs were selected for further validation by examining their expressions in LNCaP cells under DHT stimulation, and in PCa samples and cell lines. Among them, RP1-4514.2, LINC01138, SUZ12P1 and KLKP1 were validated as directly AR-targeted lncRNAs by ChIP-PCR. Then we conducted a bioinformatic analysis to identify lncRNAs as putative prognostic and therapeutic targets by using TCGA data. Three androgen-responsive lncRNAs, LINC01138, SUZ12P1 and SNHG1 showed association with gleason score and pT-stage. The biological functions of LINC01138 and SUZ12P1 were also evaluated, both lncRNAs promoted the proliferation and inhibited apoptosis of PCa. These results provide potent information for exploring potential biomarkers and therapeutic targets for prostate cancer, especially for castration-resistant PCa. PMID- 27556363 TI - Impact of Hearing Aid Technology on Outcomes in Daily Life II: Speech Understanding and Listening Effort. AB - OBJECTIVES: Modern hearing aid (HA) devices include a collection of acoustic signal-processing features designed to improve listening outcomes in a variety of daily auditory environments. Manufacturers market these features at successive levels of technological sophistication. The features included in costlier premium hearing devices are designed to result in further improvements to daily listening outcomes compared with the features included in basic hearing devices. However, independent research has not substantiated such improvements. This research was designed to explore differences in speech-understanding and listening-effort outcomes for older adults using premium-feature and basic-feature HAs in their daily lives. DESIGN: For this participant-blinded, repeated, crossover trial 45 older adults (mean age 70.3 years) with mild-to-moderate sensorineural hearing loss wore each of four pairs of bilaterally fitted HAs for 1 month. HAs were premium- and basic-feature devices from two major brands. After each 1-month trial, participants' speech-understanding and listening-effort outcomes were evaluated in the laboratory and in daily life. RESULTS: Three types of speech understanding and listening-effort data were collected: measures of laboratory performance, responses to standardized self-report questionnaires, and participant diary entries about daily communication. The only statistically significant superiority for the premium-feature HAs occurred for listening effort in the loud laboratory condition and was demonstrated for only one of the tested brands. CONCLUSIONS: The predominant complaint of older adults with mild-to moderate hearing impairment is difficulty understanding speech in various settings. The combined results of all the outcome measures used in this research suggest that, when fitted using scientifically based practices, both premium- and basic-feature HAs are capable of providing considerable, but essentially equivalent, improvements to speech understanding and listening effort in daily life for this population. For HA providers to make evidence-based recommendations to their clientele with hearing impairment it is essential that further independent research investigates the relative benefit/deficit of different levels of hearing technology across brands and manufacturers in these and other real-world listening domains. PMID- 27556362 TI - Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma. AB - Ependymomas in children can arise throughout all compartments of the central nervous system (CNS). Highly malignant paediatric ependymoma subtypes are Group A tumours of the posterior fossa (PF-EPN-A) and RELA-fusion positive (ST-EPN-RELA) tumours in the supratentorial compartment. It was repeatedly reported in smaller series that accumulation of p53 is frequently observed in ependymomas and that immunohistochemical staining correlates with poor clinical outcome, while TP53 mutations are rare. Our TP53 mutation analysis of 130 primary ependymomas identified a mutation rate of only 3%. Immunohistochemical analysis of 398 ependymomas confirmed previous results correlating the accumulation of p53 with inferior outcome. Among the p53-positive ependymomas, the vast majority exhibited a RELA fusion leading to the hypothesis that p53 inactivation might be linked to RELA positivity.In order to assess the potential of p53 reactivation through MDM2 inhibition in ependymoma, we evaluated the effects of Actinomycin-D and Nutlin-3 treatment in two preclinical ependymoma models representing the high-risk subtypes PF-EPN-A and ST-EPN-RELA. The IC-50 of the agent as determined by metabolic activity assays was in the lower nano-molar range (0.2-0.7 nM). Transcriptome analyses of high-dose (100 nM), low-dose (5 nM) and non-treated cells revealed re-expression of p53 dependent genes including p53 upregulated modulator of apoptosis (PUMA) after low-dose treatment. At the protein level, we validated the Actinomycin-D induced upregulation of PUMA, and of p53 interaction partners MDM2 and p21. Proapoptotic effects of low-dose application of the agent were confirmed by flow cytometry. Thus, Actinomycin-D could constitute a promising therapeutic option for ST-EPN-RELA ependymoma patients, whose tumours frequently exhibit p53 inactivation. PMID- 27556364 TI - Progressive Hearing Loss in Early Childhood. AB - OBJECTIVES: Deterioration in hearing thresholds in children is of concern due to the effect on language development. Before universal newborn hearing screening (UNHS), accurate information on the progression of hearing loss was difficult to obtain due to limited information on hearing loss onset. The objective of this population-based study was to document the proportion of children who experienced progressive loss in a cohort followed through a UNHS program in one region of Canada. We explored risk factors for progression including risk indicators, audiologic, and clinical characteristics of children. We also investigated deterioration in hearing as a function of age. For this study, two working definitions of progressive hearing loss were adopted: (1) a change of >=20 dB in the 3 frequencies (500, 1000, and 2000 Hz) pure-tone average, and (2) a decrease of >=10 dB at two or more adjacent frequencies between 500 and 4000 Hz or a decrease in 15 dB at one octave frequency in the same frequency range. DESIGN: Population-based data were collected prospectively on a cohort of children identified from 2003 to 2013 after the implementation of UNHS. Clinical characteristics including risk indicators (as per Joint Committee on Infant Hearing), age at diagnosis, type and severity of hearing loss, and initial audiologic information were recorded when children were first identified with hearing loss. Serial audiometric results were extracted from the medical charts for this study. Differences between children with progressive and stable hearing loss were explored using chi tests. Association between risk indicators and progressive hearing loss was assessed through logistic regression. The cumulative amount of deterioration in hearing from 1 to 4 years of age was also examined. RESULTS: Our analysis of 330 children (251 exposed to screening) with detailed audiologic records showed that 158 (47.9%) children had some deterioration (at least >=10 dB and) in hearing thresholds in at least one ear. The 158 children included 76 (48.1%) with >=20 dB loss in pure-tone average in at least one ear and 82 (51.9%) with less deterioration in hearing levels (>=10 but <20 dB). In the children with progressive hearing loss, of 131 children initially diagnosed with bilateral loss, 75 (57.3%) experienced deterioration in 1 ear and 56 (112 ears; 42.7%) in both ears (total of 187 ears). Of 27 children with an initial diagnosis of unilateral loss, 25 experienced deterioration in the impaired ear and 5 in the normal-hearing ear, progressing to bilateral hearing loss. Within 4 years after diagnosis, the mean decrease in hearing for children with progressive loss was 25.9 dB (SD: 16.4) in the right ear and 28.3 dB (SD: 12.9) in the left ear. We explored the risk factors for hearing loss identified by Joint Committee on Infant Hearing where there were sufficient numbers in our sample. On multivariate analysis, there was no statistically significant relationship between most risk indicators examined (neonatal intensive care unit admission, family history, syndromes, and postnatal infections) and the likelihood of progressive loss. However, the presence of craniofacial anomalies was inversely associated with risk of progressive hearing loss (odds ratio = 0.27; 95% confidence interval: 0.10, 0.71; p = 0.01), that is, these children were more likely to have stable hearing. CONCLUSIONS: Given that almost half of the children in this cohort experienced deterioration in hearing, close postneonatal monitoring of hearing following early hearing loss identification is essential to ensure optimal amplification and therapy. PMID- 27556365 TI - Human Envelope Following Responses to Amplitude Modulation: Effects of Aging and Modulation Depth. AB - OBJECTIVE: To record envelope following responses (EFRs) to monaural amplitude modulated broadband noise carriers in which amplitude modulation (AM) depth was slowly changed over time and to compare these objective electrophysiological measures to subjective behavioral thresholds in young normal hearing and older subjects. DESIGN: PARTICIPANTS: three groups of subjects included a young normal hearing group (YNH 18 to 28 years; pure-tone average = 5 dB HL), a first older group ("O1"; 41 to 62 years; pure-tone average = 19 dB HL), and a second older group ("O2"; 67 to 82 years; pure-tone average = 35 dB HL). Electrophysiology: In condition 1, the AM depth (41 Hz) of a white noise carrier, was continuously varied from 2% to 100% (5%/s). EFRs were analyzed as a function of the AM depth. In condition 2, auditory steady-state responses were recorded to fixed AM depths (100%, 75%, 50%, and 25%) at a rate of 41 Hz. Psychophysics: A 3 AFC (alternative forced choice) procedure was used to track the AM depth needed to detect AM at 41 Hz (AM detection). The minimum AM depth capable of eliciting a statistically detectable EFR was defined as the physiological AM detection threshold. RESULTS: Across all ages, the fixed AM depth auditory steady-state response and swept AM EFR yielded similar response amplitudes. Statistically significant correlations (r = 0.48) were observed between behavioral and physiological AM detection thresholds. Older subjects had slightly higher (not significant) behavioral AM detection thresholds than younger subjects. AM detection thresholds did not correlate with age. All groups showed a sigmoidal EFR amplitude versus AM depth function but the shape of the function differed across groups. The O2 group reached EFR amplitude plateau levels at lower modulation depths than the normal hearing group and had a narrower neural dynamic range. In the young normal hearing group, the EFR phase did not differ with AM depth, whereas in the older group, EFR phase showed a consistent decrease with increasing AM depth. The degree of phase change (or phase slope) was significantly correlated to the pure tone threshold at 4 kHz. CONCLUSIONS: EFRs can be recorded using either the swept modulation depth or the discrete AM depth techniques. Sweep recordings may provide additional valuable information at suprathreshold intensities including the plateau level, slope, and dynamic range. Older subjects had a reduced neural dynamic range compared with younger subjects suggesting that aging affects the ability of the auditory system to encode subtle differences in the depth of AM. The phase-slope differences are likely related to differences in low and high frequency contributions to EFR. The behavioral-physiological AM depth threshold relationship was significant but likely too weak to be clinically useful in the present individual subjects who did not suffer from apparent temporal processing deficits. PMID- 27556366 TI - Insight into the Kluyveromyces lactis Pdr1p regulon. AB - The overexpression of efflux pumps is an important mechanism leading to the development of multidrug resistance phenomenon. The transcription factor KlPdr1p, belonging to the Zn2Cys6 family, is a central regulator of efflux pump expression in Kluyveromyces lactis. To better understand how KlPDR1-mediated drug resistance is achieved in K. lactis, we used DNA microarrays to identify genes whose expression was affected by deletion or overexpression of the KlPDR1 gene. Eighty nine targets of the KlPDR1 were identified. From those the transcription of 16 genes was induced in the transformant overexpressing KlPDR1* and simultaneously repressed in the Klpdr1Delta deletion mutant. Almost all of these genes contain putative binding motifs for the AP-1-like transcription factors in their promoters. Furthermore, we studied the possible interplay between KlPdr1p and KlYap1p transcription factors. Our results show that KlYap1p does not significantly contribute to the regulation of KlPDR1 gene expression in the presence of azoles. However, KlPDR1 expression markedly increased in the presence of hydrogen peroxide and hinged upon the presence of KlYap1p. Our results show that although both KlPdr1p and KlYap1p transcription factors are involved in the control of K. lactis multidrug resistance, further studies will be needed to determine their interplay. PMID- 27556367 TI - Baylisascaris procyonis Demography and Egg Production in a California Raccoon Population. AB - California has more reported human raccoon roundworm cases than any other state due to large and overlapping human and raccoon populations. Infection by this parasite, Baylisascaris procyonis , is relatively benign in raccoons but can cause severe pathology in other species. Disease risk is driven by environmental egg contamination which increases with raccoon density, worm intensity, and worm prevalence. To improve knowledge about risk to humans and other species, 189 raccoons from southern California were examined to investigate how host age and season affect worm abundance, demography, and fecundity. Adult worms were present in animals as young as 10 wk and 100% of 4-mo-old raccoons were infected. Although 80% of sampled raccoons hosted adult B. procyonis , prevalence and abundance were lower in older animals. There were more worms in juvenile than in adult raccoons, resulting in a convex age-intensity profile. Coupled with raccoon demography, this drove fall peaks in parasite abundance and egg production. Eggs per-gram feces averaged 4,606 +/- 661 (SE), and this output increased with worm intensity, with no evidence that crowding reduced parasite size or fecundity. High parasite egg outputs from hosts in this California raccoon population increase human exposure risk, and this risk could be reduced by management strategies that target heavily infected juvenile raccoons. PMID- 27556368 TI - Immunogenetics of multiple sclerosis: more questions than answers. PMID- 27556369 TI - Sometimes less is more in multiple sclerosis drug switching. PMID- 27556370 TI - The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population. AB - OBJECTIVE: To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. METHODS: We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. RESULTS: We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. CONCLUSIONS: Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds. PMID- 27556371 TI - Patients' satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis. AB - OBJECTIVE: The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients' satisfaction with the treatment must be taken into consideration. METHODS: Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. RESULTS: One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. CONCLUSION: Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD. PMID- 27556372 TI - Prevalence and predictors of post stroke depression among elderly stroke survivors. AB - OBJECTIVE: To identify the prevalence of post stroke depression (PSD) and their socio-demographic and clinical predictors among elderly stroke survivors after hospital discharge to home. METHODS: In this cross-sectional study, 90 elderly stroke survivors were evaluated 14 days after hospital discharge with the following scales: National Institutes of Health Stroke Scale, Functional Independence Measure, and Geriatric Depression Scale - 15 items (GDS-15). PSD was defined as a score > 5 on GDS-15. After univariate analyses, a multivariate logistic regression model was built to identify independent predictors of PSD. RESULTS: Fourteen days after hospital discharge, 27.7% (95%CI 18.1 to 37.2) of elderly stroke survivors had PSD. Functional dependence was the only independent predictor of PSD (OR: 1.04 95%CI: 1.01 to 1.09; p = 0.02). CONCLUSION: After stroke, depressive symptoms are common among elderly survivors. The degree of functional dependency is the main predictor of PSD among elderly stroke patients in Brazil. PMID- 27556373 TI - Serum levels of adiponectin, CCL3/MIP-1alpha, and CCL5/RANTES discriminate migraine from tension-type headache patients. AB - OBJECTIVES: Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. METHODS: This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. RESULTS: We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1alpha (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. CONCLUSIONS: This study showed higher CCL3/MIP-1alpha, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches. PMID- 27556374 TI - Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children. AB - This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons. PMID- 27556375 TI - Performance of language tasks in patients with ruptured aneurysm of the left hemisphere worses in the post-surgical evaluation. AB - OBJECTIVE: To assess the language and verbal fluency performance in aneurismal SAH pre- and post-surgery in patients caused by an aneurysm of the anterior communicating artery (AcomA), left middle cerebral artery (L-MCA) and left posterior comunicating artery (L-PcomA). METHODS: Assessment in 79 patients with SAH, on two occasions: pre- and post surgical treatment. They were divided into three groups by the aneurysms' location. RESULTS: Deterioration is detected in the performance of all patients during the post-surgical period; L-MCA aneurysm patients displayed a reduction in verbal naming and fluency; L-PcomA patients deteriorated in the written language and fluency tasks. CONCLUSION: After the surgical procedure the patients decreased in various language tasks and these differences in performance being directly related to the location of the aneurysm. PMID- 27556376 TI - Hemotransfusion and mechanical ventilation time are associated with intra hospital mortality in patients with traumatic brain injury admitted to intensive care unit. AB - OBJECTIVE: To identify the factors associated with the intra-hospital mortality in patients with traumatic brain injury (TBI) admitted to intensive care unit (ICU). METHODS: The sample included patients with TBI admitted to the ICU consecutively in a period of one year. It was defined as variables the epidemiological characteristics, factors associated with trauma and variables arising from clinical management in the ICU. RESULTS: The sample included 87 TBI patients with a mean age of 28.93 +/- 12.72 years, predominantly male (88.5%). The intra-hospital mortality rate was of 33.33%. The initial univariate analysis showed a significant correlation of intra-hospital death and the following variables: the reported use of alcohol (p = 0.016), hemotransfusion during hospitalization (p = 0.036), and mechanical ventilation time (p = 0.002). CONCLUSION: After multivariate analysis, the factors associated with intra hospital mortality in TBI patients admitted to the intensive care unit were the administration of hemocomponents and mechanical ventilation time. PMID- 27556377 TI - Safety of switching from natalizumab straight into fingolimod in a group of JCV positive patients with multiple sclerosis. AB - OBJECTIVE: To assess safety of the switch between natalizumab and fingolimod without a washout period. METHODS: Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. RESULTS: After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. CONCLUSION: Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching. PMID- 27556378 TI - Cross-cultural adaptation to Brazilian Portuguese of the Michigan Neuropathy Screening Instrument: MNSI-Brazil. AB - Since 1994, the University of Michigan Diabetes Research and Training Center proposed an instrument to measure neuropathies not yet adapted to use in Brazil. Then, this study aimed to adapt cross-culturally the Michigan Neuropathy Screening Instrument (MNSI) into Brazilian Portuguese, verifying its reliability. Thirty diabetic patients were initially evaluated with the adapted version after completed the essential steps to accomplish the cross-cultural adaptation. Twenty two of them completed the procedures to repeat the measured scores after day 1 (trial 0). The repeated measurements were tested at days 2 or 3 (trial 1) by another rater (inter-rater reliability) and retested at day 20 (trial 2) by one of the attended raters (inter-test reliability). There were not great semantics, linguistics or cultural differences between two versions and excellent reliability was confirmed by intra-class correlation coefficient above 0.840. It was concluded that MNSI in the Brazilian version is reliable and it is ready to use. PMID- 27556379 TI - Are astrocytes executive cells within the central nervous system? AB - Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson's disease, Alzheimer's dementia, Huntington's dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well. PMID- 27556380 TI - Lumbar puncture in patients using anticoagulants and antiplatelet agents. AB - The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks. PMID- 27556381 TI - Harbinger of storm: influence of Oliver Sacks on levodopa therapy in early 1970s. AB - Most known by his literary ability, the words of the neurologist Oliver Sacks (1933-2015) also had an impact on scientific community about the role of levodopa on parkinsonisms. Different from the most authors and based on his experience described on the book "Awakenings", he had a pessimistic opinion about levodopa, which was related on many articles written by himself and colleagues in early 1970s. We reviewed the scientific contribution of Oliver Sacks associated to levodopa therapy on parkinsonisms, and how he advised caution with its complications before the majority of physicians. PMID- 27556382 TI - Early reperfusion therapy in acute ischemic stroke after recent myocardial infarction. PMID- 27556383 TI - Guillain-Barre syndrome and Zika virus infection. PMID- 27556384 TI - Is heart rate variability a feasible method to determine anaerobic threshold in progressive resistance exercise in coronary artery disease? AB - BACKGROUND: Recent studies have shown that the magnitude of the metabolic and autonomic responses during progressive resistance exercise (PRE) is associated with the determination of the anaerobic threshold (AT). AT is an important parameter to determine intensity in dynamic exercise. OBJECTIVES: To investigate the metabolic and cardiac autonomic responses during dynamic resistance exercise in patients with Coronary Artery Disease (CAD). METHOD: Twenty men (age = 63+/-7 years) with CAD [Left Ventricular Ejection Fraction (LVEF) = 60+/-10%] underwent a PRE protocol on a leg press until maximal exertion. The protocol began at 10% of One Repetition Maximum Test (1-RM), with subsequent increases of 10% until maximal exhaustion. Heart Rate Variability (HRV) indices from Poincare plots (SD1, SD2, SD1/SD2) and time domain (rMSSD and RMSM), and blood lactate were determined at rest and during PRE. RESULTS: Significant alterations in HRV and blood lactate were observed starting at 30% of 1-RM (p<0.05). Bland-Altman plots revealed a consistent agreement between blood lactate threshold (LT) and rMSSD threshold (rMSSDT) and between LT and SD1 threshold (SD1T). Relative values of 1 RM in all LT, rMSSDT and SD1T did not differ (29%+/-5 vs 28%+/-5 vs 29%+/-5 Kg, respectively). CONCLUSION: HRV during PRE could be a feasible noninvasive method of determining AT in CAD patients to plan intensities during cardiac rehabilitation. PMID- 27556385 TI - Analysis of agreement between cardiac risk stratification protocols applied to participants of a center for cardiac rehabilitation. AB - BACKGROUND: Cardiac risk stratification is related to the risk of the occurrence of events induced by exercise. Despite the existence of several protocols to calculate risk stratification, studies indicating that there is similarity between these protocols are still unknown. OBJECTIVE: To evaluate the agreement between the existing protocols on cardiac risk rating in cardiac patients. METHOD: The records of 50 patients from a cardiac rehabilitation program were analyzed, from which the following information was extracted: age, sex, weight, height, clinical diagnosis, medical history, risk factors, associated diseases, and the results from the most recent laboratory and complementary tests performed. This information was used for risk stratification of the patients in the protocols of the American College of Sports Medicine, the Brazilian Society of Cardiology, the American Heart Association, the protocol designed by Frederic J. Pashkow, the American Association of Cardiovascular and Pulmonary Rehabilitation, the Societe Francaise de Cardiologie, and the Sociedad Espanola de Cardiologia. Descriptive statistics were used to characterize the sample and the analysis of agreement between the protocols was calculated using the Kappa coefficient. Differences were considered with a significance level of 5%. RESULTS: Of the 21 analyses of agreement, 12 were considered significant between the protocols used for risk classification, with nine classified as moderate and three as low. No agreements were classified as excellent. Different proportions were observed in each risk category, with significant differences between the protocols for all risk categories. CONCLUSION: The agreements between the protocols were considered low and moderate and the risk proportions differed between protocols. PMID- 27556386 TI - Family's presence associated with increased physical activity in patients with acute stroke: an observational study. AB - BACKGROUND: Inherent differences in organization of stroke care and rehabilitation practices in various settings influence the activity levels of patients in the hospital. The majority of published studies have been carried out in developed countries such as the United States, United Kingdom, Australia, Switzerland and Belgium; however, data from developing countries are scarce. OBJECTIVE: To measure the amount and nature of physical activity of patients admitted to medical wards of Indian hospitals and to assess the association between family presence and the patient and between the patient's functional status and their physical activity level. METHOD: This is an observational behavioral mapping study. A trained physical therapist recorded the patients' (N=47) physical activity level through direct observation in the ward using a predetermined observation scheme. RESULTS: Participants were found inactive and alone for 19% (inter quartile range [IQR] 12-36%) and 15% (IQR 10-19%) of the time during the day, respectively. They spent 46% (IQR 31-55%) of the time in therapeutic activities and 31% (IQR 22-34%) of the time in non-therapeutic activities. The family was present with patients 50% of the time during the day. Family presence with the patient and the patient's moderate dependence in daily activities are positively associated with their activity levels. CONCLUSION: Patients with stroke admitted to Indian hospitals spent less time being inactive and alone and more time with family participating in therapeutic activities. The presence of family members with the patients during hospital stay may be a significant resource for encouraging patients to be more active. PMID- 27556387 TI - High voltage pulsed current in collagen realignment, synthesis, and angiogenesis after Achilles tendon partial rupture. AB - OBJECTIVE: To verify the efficacy of high voltage pulsed current in collagen realignment and synthesis and in angiogenesis after the partial rupturing of the Achilles tendon in rats. METHOD: Forty male Wistar rats were randomized into four groups of 10 animals each: sham, cathodic stimulation, anodic stimulation, and alternating stimulation. Their Achilles tendons were submitted to direct trauma by a free-falling metal bar. Then, the treatment was administered for six consecutive days after the injury. In the simulation group, the electrodes were positioned on the animal, but the device remained off for 30 minutes. The other groups used a frequency of 120 pps, sensory threshold, and the corresponding polarity. On the seventh day, the tendons were removed and sent for histological slide preparation for birefringence and Picrosirius Red analysis and for blood vessel quantification. RESULTS: No significant difference was observed among the groups regarding collagen realignment (types I or III collagen) or quantity of blood vessels. CONCLUSION: High voltage pulsed current for six consecutive days was not effective in collagen realignment, synthesis, or angiogenesis after the partial rupturing of the Achilles tendon in rats. PMID- 27556388 TI - Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial. AB - OBJECTIVE: To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF) following myocardial infarction. METHOD: Twenty-seven male adult Wistar rats were randomized to CHF group (n=12) or Sham group (n=15). Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. RESULTS: The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs) and the total lung capacity (TLC) were lower (40% and 27%, respectively) in the CHF rats when compared to the Sham group (P<0.01). There was also an increase in tissue resistance (Gti) and elastance (Hti) (28% and 45%, respectively) in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01), while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02) in the CHF group when compared to the control. Pearson's correlation coefficient showed a negative association between pulmonary edema and Crs (r=-0.70, P=0.0001) and between pulmonary edema and TLC (r=-0.67, P=0.0034). Pulmonary edema correlated positively with Gti (r=0.68, P=0.001) and Hti (r=0.68, P=0.001). Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001). CONCLUSION: Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions. PMID- 27556389 TI - Effect of a single session of ear acupuncture on pain intensity and postural control in individuals with chronic low back pain: a randomized controlled trial. AB - BACKGROUND: Ear Acupuncture (EA) is a form of acupuncture in which needles are applied to the external ear and has been used in multiple painful conditions. Low back pain (LBP) is highly prevalent in active individuals and causes high economic burden to health systems worldwide. LBP affects the person's ability to keep balance, especially in challenging conditions. OBJECTIVE: The aim of the study was to examine the effects of a single session of EA on pain intensity and body sway during postural tasks. METHOD: Eighty adults with LBP and pain intensity equal to or greater than 4 (0-10 scale) were randomly allocated (1:1) to EA group (EAG) or placebo group (PG). Initially, the level of pain intensity was assessed. Next, participants stood still on a force plate either with feet in parallel or in semi-tandem and with eyes open or closed. Then, the EAG was treated with EA for 20 min and the PG was treated with detuned ultrasound. After the treatment, pain intensity was assessed again and the postural test was repeated. Pain intensity was the primary outcome and center of pressure sway area and speed were the secondary outcomes measured. RESULTS: Results revealed that pain intensity decreased in both groups after treatment, but decreased more in the EAG. For postural control, no effect of treatment and no interaction between treatment and postural condition on body sway were found. CONCLUSION: Those findings indicate that EA is better than placebo to reduce pain, but neither treatment has any effect on postural control. PMID- 27556390 TI - Effects of non-invasive ventilation and posture on chest wall volumes and motion in patients with amyotrophic lateral sclerosis: a case series. AB - BACKGROUND: The effects of non-invasive ventilation (NIV) on the breathing pattern and thoracoabdominal motion of patients with amyotrophic lateral sclerosis (ALS) are unknown. OBJECTIVES: 1) To analyze the influence of NIV on chest wall volumes and motion assessed by optoelectronic plethysmography in ALS patients and 2) to compare these parameters in the supine and sitting positions to those of healthy individuals (without NIV). METHOD: Nine ALS patients were evaluated in the supine position using NIV. In addition, the ALS patients and nine healthy individuals were evaluated in both sitting and supine positions. Statistical analysis was performed using the paired Student t-test or Wilcoxon test and the Student t-test for independent samples or Mann-Whitney U test. RESULTS: Chest wall volume increased significantly with NIV, mean volume=0.43 (SD=0.16)L versus 0.57 (SD=0.19)L (p=0.04). No significant changes were observed for the pulmonary rib cage, abdominal rib cage, or abdominal contribution. The index of the shortening velocity of the diaphragmatic muscle, mean=0.15 (SD=0.05)L/s versus 0.21 (SD=0.05)L/s (p<0.01), and abdominal muscles, mean=0.09 (SD=0.02)L/s versus 0.14 (SD=0.06)L/s (p<0.01), increased during NIV. Comparisons between the supine and sitting positions showed similar changes in chest wall motion in both groups. However, the ALS patients presented a significantly lower contribution of the abdomen in the supine position compared with the controls, mean=56 (SD=13) versus 69 (SD=10) (p=0.02). CONCLUSIONS: NIV improved chest wall volumes without changing the contribution of the chest wall compartment in ALS patients. In the supine position, ALS patients had a lower contribution of the abdomen, which may indicate early diaphragmatic dysfunction. PMID- 27556391 TI - Posture and mobility of the upper body quadrant and pulmonary function in COPD: an exploratory study. AB - BACKGROUND: There is limited evidence regarding interactions between pulmonary (dys)function, posture, and mobility of the upper body quadrant in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: This exploratory study aimed to investigate whether postural alignment and mobility of the upper quadrant are related to changes in pulmonary function and compare such variables between patients with COPD and healthy individuals. METHOD: Fifteen patients with COPD (67.93+/-9.71yrs) and 15 healthy controls (66.80+/-7.47yrs) participated. Pulmonary function (FEV1, FVC) was assessed with spirometry. Alignment and mobility of the head, thoracic spine, and shoulder were assessed using digital photographs. Pectoralis minor muscle (PmM) length and thoracic excursion were assessed with a measuring tape. Groups were compared and linear regression analyses were used to assess potential relationships between postural and mobility variables and pulmonary function. RESULTS: Patients with COPD were more likely to have a forward head position at maximal protraction (28.81+/-7.30o vs. 35.91+/-8.56o, p=0.02) and overall mobility of the head (21.81+/-10.42o vs. 13.40+/-7.84o, p=0.02) and a smaller range of shoulder flexion (136.71+/-11.91o vs. 149.08+/-11.58o, p=0.01) than controls. Patients' non-dominant PmM length and maximal head protraction were predictors of FEV1 (r2adjusted=0.34). These variables, together with the upper thoracic spine at maximal flexion and thoracic kyphosis at maximal extension, were predictors of FVC (r2adjusted=0.68). CONCLUSION: Our findings suggest that impaired pulmonary function is associated with muscle length and mobility adaptations. Further studies are needed to understand the underlying mechanisms and clinical value of these relationships. PMID- 27556392 TI - Health, function and disability in stroke patients in the community. AB - BACKGROUND: Stroke patients commonly have impairments associated with reduction in functionality. Among these impairments, the motor impairments are the most prevalent. The functional profile of these patients living in the community who are users of the primary health-care services in Brazil has not yet been established. OBJECTIVE: To describe the functional profile of stroke patients who are users of the primary health-care services in Brazil, looking at one health care unit in the city of Belo Horizonte, Brazil. METHOD: From medical records and home visits, data were collected regarding health status, assistance received following the stroke, personal and environmental contextual factors, function and disability, organized according to the conceptual framework of the International Classification of Functioning, Disability and Health (ICF). Test and instruments commonly applied in the assessment of stroke patients were used. RESULTS: Demographic data from all stroke patients who were users of the health-care unit (n=44, age: 69.23+/-13.12 years and 67+/-66.52 months since the stroke) participated of this study. Most subjects presented with disabilities, as changes in emotional function, muscle strength, and mobility, risks of falling during functional activities, negative self-perception of quality of life, and perception of the environment factors were perceived as obstacles. The majority of the patients used the health-care unit to renew drug prescriptions, and did not receive any information on stroke from health professionals, even though patients believed it was important for patients to receive information and to provide clarifications. CONCLUSION: Stroke patients who used primary health-care services in Brazil have chronic disabilities and health needs that require continuous health attention from rehabilitation professionals. All of these health needs should be considered by health professionals to provide better management as part of the integral care of stroke patients, as recommended by the clinical practice guidelines for stroke rehabilitation. PMID- 27556393 TI - Effects of 10,000 steps a day on physical and mental health in overweight participants in a community setting: a preliminary study. AB - BACKGROUND: Being overweight is associated not only with physical health problems, but also with risk of mental health problems. Increased physical activity (PA) has been recommended for the prevention of cardiovascular disease; however, little is known about the effect of walking on physical and mental health outcomes. OBJECTIVE: The purpose of the study was to explore the effectiveness of a pedometer-based PA intervention on physical and mental health states. METHOD: Thirty-five overweight participants with body mass index (BMI) >=25 kg*m-2 were selected and assigned to a 12-week pedometer-based walking program (10,000 steps*d-1). The profile of mood states, BMI, waist circumference (WC), body fat percentage (%BF), and lean body mass (LBM) were measured before and after the 12-week intervention. The number of step counts was recorded 5 days a week in a diary booklet. RESULTS: The 30 participants who accumulated 10,000 steps*d-1 had significantly lower anxiety, depression, anger, fatigue, confusion, and total mood distress scores compared with measurements taken prior to the intervention. Further, the participants had higher vigor scores compared to baseline. Regarding physical health, the participants who accrued 10,000 steps a day had significantly lower body weight, WC, BMI, and %BP. After adjustment for gender, height, and daily steps at follow-up, changes in WC were negatively associated with depression, fatigue, confusion, and total mood distress. CONCLUSIONS: An increase in PA by accumulating at least 10,000 steps*d-1 over a 12-week period improves physical and mood states in sedentary, overweight individuals. PMID- 27556394 TI - Emergence of psychotic content in psychotherapy: An exploratory qualitative analysis of content, process, and therapist variables in a single case study. AB - OBJECTIVE: Emerging integrative metacognitive therapies for schizophrenia seek to promote subjective aspects of recovery. Beyond symptom remission, they are concerned with shared meaning-making and intersubjective processes. It is unclear, however, how such therapies should understand and respond to psychotic content that threatens meaning-making in therapeutic contexts. Accordingly, we sought to understand what factors precede and potentially trigger psychotic content within psychotherapy and what aids in resolution and return to meaning making. METHOD: Forty-eight transcripts from a single psychotherapy case were analyzed with thematic analysis. Passages of delusional or disorganized content were identified and themes present prior to the emergence and resolution of such material were identified and coded. RESULTS: Themes that preceded the emergence of psychotic content varied across early, middle, and late phases of therapy. Material related to the patient's experience of inadequacy and potential vulnerability, therapist setting boundaries within the therapeutic relationship and making challenges appeared to trigger psychotic content, especially early in treatment. CONCLUSIONS: Psychotic content may emerge in session following identifiable antecedents which change over phases of therapy. Attending to psychotic content by assuming a non-hierarchical stance and not dismissing psychotic content may aid in maintaining intersubjectivity and support patient's movements toward recovery in integrative metacognitive therapies. PMID- 27556395 TI - Direct to Consumer Prescription Drug Advertising: More Harm Than Good. PMID- 27556396 TI - Rational Selection of the 3D Structure of Biomacromolecules for Molecular Docking Studies on the Mechanism of Endocrine Disruptor Action. AB - Molecular modeling has become an essential tool in predicting and simulating endocrine disrupting effects of chemicals. A key prerequisite for successful application of molecular modeling lies in the correctness of 3D structure for biomacromolecules to be simulated. To date, there are several databases that can provide the experimentally-determined 3D structures. However, commonly, there are many challenges or disadvantageous factors, e.g., (a) lots of 3D structures for a given biomacromolecular target in the protein database; (b) the quality variability for those structures; (c) belonging to different species; (d) mutant amino acid residue in key positions, and so on. Once an inappropriate 3D structure of a target biomacromolecule was selected in molecular modeling, the accuracy and scientific nature of the modeling results could be inevitably affected. In this article, based on literature survey and an analysis of the 3D structure characterization of biomacromolecular targets belonging to the endocrine system in protein databases, six principles were proposed to guide the selection of the appropriate 3D structure of biomacromolecules. The principles include considering the species diversity, the mechanism of action, whether there are mutant amino acid residues, whether the number of protein chains is correct, the degree of structural similarity between the ligand in 3D structure and the target compounds, and other factors, e.g., the experimental pH conditions of the structure determined process and resolution. PMID- 27556397 TI - A Checkpoint-Related Function of the MCM Replicative Helicase Is Required to Avert Accumulation of RNA:DNA Hybrids during S-phase and Ensuing DSBs during G2/M. AB - The Mcm2-7 complex is the catalytic core of the eukaryotic replicative helicase. Here, we identify a new role for this complex in maintaining genome integrity. Using both genetic and cytological approaches, we find that a specific mcm allele (mcm2DENQ) causes elevated genome instability that correlates with the appearance of numerous DNA-damage associated foci of gammaH2AX and Rad52. We further find that the triggering events for this genome instability are elevated levels of RNA:DNA hybrids and an altered DNA topological state, as over-expression of either RNaseH (an enzyme specific for degradation of RNA in RNA:DNA hybrids) or Topoisomerase 1 (an enzyme that relieves DNA supercoiling) can suppress the mcm2DENQ DNA-damage phenotype. Moreover, the observed DNA damage has several additional unusual properties, in that DNA damage foci appear only after S-phase, in G2/M, and are dependent upon progression into metaphase. In addition, we show that the resultant DNA damage is not due to spontaneous S-phase fork collapse. In total, these unusual mcm2DENQ phenotypes are markedly similar to those of a special previously-studied allele of the checkpoint sensor kinase ATR/MEC1, suggesting a possible regulatory interplay between Mcm2-7 and ATR during unchallenged growth. As RNA:DNA hybrids primarily result from transcription perturbations, we suggest that surveillance-mediated modulation of the Mcm2-7 activity plays an important role in preventing catastrophic conflicts between replication forks and transcription complexes. Possible relationships among these effects and the recently discovered role of Mcm2-7 in the DNA replication checkpoint induced by HU treatment are discussed. PMID- 27556398 TI - Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Executive dysfunction is common in patients with ALS, with up to 50% of patients performing within an impaired range. There is evidence that social cognitive deficits associated with ALS are a function of deficits in executive function. The 'Reading the Mind in the Eyes' Test is a recognized test of social cognitive function, although the reliability of this instrument remains to be established. METHODOLOGY: Patients with ALS (n = 106), and age and IQ matched controls (n = 50) were recruited and asked to perform the Reading the Mind in the Eyes Test as part of an on-going population-based study of cognitive function. ALS patients were sub-stratified based on the presence, and/or extent of executive dysfunction. RESULTS: Cronbach's Alpha of .73 was observed, indicating good reliability on this measure. Split-half reliability analysis further confirms these findings (p = 0.826). The Reading the Mind in the Eyes test had excellent psychometric properties when discriminating between ALS patients who are cognitively intact, and those who have executive impairment, with an overall medium difficulty. There was a large magnitude significant difference between patients and controls (p< 0.001; eta2 = .19). Post-hoc analysis revealed that controls performed significantly higher than patients with executive impairment (p< 0.001), and patients with single executive deficits (p = 0.002). CONCLUSION: Executive dysfunction impacts on social cognitive performance. This study contributes not only to the psychometric knowledge of this measure, but also to the usability, efficacy, and reliability of social cognitive assessment in ALS. Using population-specific normative data, we confirm the Reading the Mind in the Eyes Test is a reliable measure of social cognitive processes in ALS. PMID- 27556399 TI - Preliminary Validation of a High Docosahexaenoic Acid (DHA) and alpha-Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts. AB - Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (>=C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend. PMID- 27556401 TI - Patterns of Family Formation in Response to Sex Ratio Variation. AB - The impact that unbalanced sex ratios have on health and societal outcomes is of mounting contemporary concern. However, it is increasingly unclear whether it is male- or female-biased sex ratios that are associated with family and social instability. From a socio-demographic perspective, male-biased sex ratios leave many men unable to find a mate, elevating competition among males, disrupting family formation and negatively affecting social stability. In contrast, from a mating-market perspective, males are expected to be less willing to marry and commit to a family when the sex ratio is female-biased and males are rare. Here we use U.S. data to evaluate predictions from these competing frameworks by testing the relationship between the adult sex ratio and measures of family formation. We find that when women are rare men are more likely to marry, be part of a family and be sexually committed to a single partner. Our results do not support claims that male-biased sex ratios lead to negative family outcomes due to a surplus of unmarried men. Rather, our results highlight the need to pay increased attention to female-biased sex ratios. PMID- 27556400 TI - The Prolyl Isomerase Pin1 Promotes the Herpesvirus-Induced Phosphorylation Dependent Disassembly of the Nuclear Lamina Required for Nucleocytoplasmic Egress. AB - The nuclear lamina lines the inner nuclear membrane providing a structural framework for the nucleus. Cellular processes, such as nuclear envelope breakdown during mitosis or nuclear export of large ribonucleoprotein complexes, are functionally linked to the disassembly of the nuclear lamina. In general, lamina disassembly is mediated by phosphorylation, but the precise molecular mechanism is still not completely understood. Recently, we suggested a novel mechanism for lamina disassembly during the nuclear egress of herpesviral capsids which involves the cellular isomerase Pin1. In this study, we focused on mechanistic details of herpesviral nuclear replication to demonstrate the general importance of Pin1 for lamina disassembly. In particular, Ser22-specific lamin phosphorylation consistently generates a Pin1-binding motif in cells infected with human and animal alpha-, beta-, and gammaherpesviruses. Using nuclear magnetic resonance spectroscopy, we showed that binding of Pin1 to a synthetic lamin peptide induces its cis/trans isomerization in vitro. A detailed bioinformatic evaluation strongly suggests that this structural conversion induces large-scale secondary structural changes in the lamin N-terminus. Thus, we concluded that a Pin1-induced conformational change of lamins may represent the molecular trigger responsible for lamina disassembly. Consistent with this concept, pharmacological inhibition of Pin1 activity blocked lamina disassembly in herpesvirus-infected fibroblasts and consequently impaired virus replication. In addition, a phospho-mimetic Ser22Glu lamin mutant was still able to form a regular lamina structure and overexpression of a Ser22-phosphorylating kinase did not induce lamina disassembly in Pin1 knockout cells. Intriguingly, this was observed in absence of herpesvirus infection proposing a broader importance of Pin1 for lamina constitution. Thus, our results suggest a functional model of similar events leading to disassembly of the nuclear lamina in response to herpesviral or inherent cellular stimuli. In essence, Pin1 represents a regulatory effector of lamina disassembly that promotes the nuclear pore independent egress of herpesviral capsids. PMID- 27556402 TI - Free MoS2 Nanoflowers Grown on Graphene by Microwave-Assisted Synthesis as Highly Efficient Non-Noble-Metal Electrocatalysts for the Hydrogen Evolution Reaction. AB - Advanced approaches to preparing non-noble-metal electrocatalysts for the hydrogen evolution reaction (HER) are considered to be a significant breakthrough in promoting the exploration of renewable resources. In this work, a hybrid material of MoS2 nanoflowers (NFs) on reduced graphene oxide (rGO) was synthesized as a HER catalyst via an environmentally friendly, efficient approach that is also suitable for mass production. Small-sized MoS2 NFs with a diameter of ca. 190 nm and an abundance of exposed edges were prepared by a hydrothermal method and were subsequently supported on rGO by microwave-assisted synthesis. The results show that MoS2 NFs were distributed uniformly on the remarkably reduced GO and preserved the outstanding original structural features perfectly. Electrochemical tests show that the as-prepared hybrid material exhibited excellent HER activity, with a small Tafel slope of 80 mV/decade and a low overpotential of 170 mV. PMID- 27556403 TI - DNA Barcoding Reveals High Cryptic Diversity in the North Eurasian Moina Species (Crustacea: Cladocera). AB - Species of the genus Moina Baird (Cladocera: Moinidae) often dominate freshwater crustacean communities in temporary water bodies. Several species of Moina are used as food for fish larvae in aquaculture, as bioindicators in toxicological studies, and as common subjects for physiological studies. The aim of this paper is to estimate biodiversity of Moina in northern Eurasia using the standard DNA barcoding approach based on the cytochrome c oxidase subunit I (COI) gene. We analysed 160 newly obtained and 157 existing COI sequences, and found evidence for 21 phylogroups of Moina, some of which were detected here for the first time. Our study confirmed the opinion that the actual species diversity of cladocerans is several times higher than is presently accepted. Our results also indicated that Moina has the second richest species diversity among the cladoceran genera (with only Daphnia O. F. Mueller having a greater diversity of species). Our study strongly supports division of Moina into two faunistic groups: European Western Siberian and Eastern Siberian-Far Eastern, with a transitional zone at the Yenisey River basin (Eastern Siberia). Here, we refrain from taxonomic descriptions of new species, as this requires a thorough morphological and taxonomic study for each putative taxon. PMID- 27556405 TI - Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function. AB - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. METHODS: We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function. RESULTS: RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2 11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (beta -2.1, 95% CI -4.0 to -0.2; beta -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (beta -3.1, 95% CI -6.1 to 0.2) with a trend for lower FEV1/FVC % predicted. CONCLUSIONS: A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population. PMID- 27556406 TI - Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest. AB - Murine norovirus-1 (MNV-1) is known to subvert host cell division inducing an accumulation of cells in the G0/G1 phase, creating conditions where viral replication is favored. This study identified that NS5 (VPg), is capable of inducing cell cycle arrest in the absence of viral replication or other viral proteins in an analogous manner to MNV-1 infection. NS5 expression induced an accumulation of cells in the G0/G1 phase in an asynchronous population by inhibiting progression at the G1/S restriction point. Furthermore, NS5 expression resulted in a down-regulation of cyclin A expression in asynchronous cells and inhibited cyclin A expression in cells progressing from G1 to S phase. The activity of NS5 on the host cell cycle occurs through an uncharacterized function. Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G0/G1 phase as identified for wild-type NS5. To the best of our knowledge, this is the first report of a VPg protein manipulating the host cell cycle. PMID- 27556404 TI - An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. AB - We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-alpha ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies. PMID- 27556407 TI - Correlation Between MRI and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer. AB - OBJECTIVE: Increased levels of tumor-infiltrating lymphocytes (TILs) positively correlate with the pathologic complete response rate and increased survival in patients with triple-negative breast cancer (TNBC). The purpose of this study was to investigate associations between TIL levels and MRI findings in patients with TNBC. MATERIALS AND METHODS: From February 2006 through December 2014, a total of 112 women with TNBC were selected for inclusion in the study. All lesions were evaluated by radiologists in accordance with the BI-RADS lexicon. Lymph node involvement and multifocality were also assessed. Tumors were divided into two groups: those with a TIL level of less than 50% were included in the group with low TIL levels (hereafter referred to as the "low-TIL group"), and those with a TIL level of 50% or more were included in the group with high TIL levels (hereafter referred to as the "high-TIL group"). Associations between TIL levels and imaging features were evaluated. RESULTS: Tumors in the high-TIL group had a more round shape (46.0%), a circumscribed margin (76.0%), homogeneous enhancement (32.0%), and absence of multifocality (88.0%) (p < 0.005). Tumors in the low-TIL group had a more irregular shape (69.3%), no circumscribed margin (79.0%), heterogeneous enhancement (75.8%), and multifocality (70.9%) (p < 0.005). CONCLUSION: The well-known typical features of TNBC on MRI, including a round shape, a circumscribed margin, homogeneous enhancement, and lack of multifocality, are a major pattern of TNBC with high TIL levels. This information could provide added diagnostic benefit for the identification of tumors with a good prognosis, which could further assist in optimal pretreatment planning. PMID- 27556409 TI - Bowl Inversion and Electronic Switching of Buckybowls on Gold. AB - Bowl-shaped pi-conjugated compounds, or buckybowls, are a novel class of sp(2) hybridized nanocarbon materials. In contrast to tubular carbon nanotubes and ball shaped fullerenes, the buckybowls feature structural flexibility. Bowl-to-bowl structural inversion is one of the unique properties of the buckybowls in solutions. Bowl inversion on a surface modifies the metal-molecule interactions through bistable switching between bowl-up and bowl-down states on the surface, which makes surface-adsorbed buckybowls a relevant model system for elucidation of the mechano-electronic properties of nanocarbon materials. Here, we report a combination of scanning tunneling microscopy (STM) measurements and ab initio atomistic simulations to identify the adlayer structure of the sumanene buckybowl on Au(111) and reveal its unique bowl inversion behavior. We demonstrate that the bowl inversion can be induced by approaching the STM tip toward the molecule. By tuning the local metal-molecule interaction using the STM tip, the sumanene buckybowl exhibits structural bistability with a switching rate that is two orders of magnitude faster than that of the stochastic inversion process. PMID- 27556408 TI - Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. OBJECTIVES: To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. METHODS: We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5 year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV1 decline based on reported exacerbations or acute respiratory events. MEASUREMENTS AND MAIN RESULTS: In subjects with COPD, exacerbations were associated with excess FEV1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23 151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV1 decline. CONCLUSIONS: Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764). PMID- 27556410 TI - Comparison of Coronary Artery Calcium Scores Between Patients With Psoriasis and Type 2 Diabetes. AB - Importance: Psoriasis is associated with an increased risk of cardiovascular diseases. Subclinical atherosclerosis in patients with psoriasis has not been compared with other conditions associated with increased cardiovascular risk and more rigorous cardiovascular disease screening, such as type 2 diabetes. Objective: To assess the burden of asymptomatic coronary atherosclerosis measured by coronary artery calcium score in patients with moderate to severe psoriasis compared with patients with type 2 diabetes and healthy controls. Design, Setting, and Participants: Three single-center, cross-sectional studies were performed in patients recruited from specialty outpatient clinics with moderate to severe psoriasis without type 2 diabetes (recruited from November 1, 2013, through April 31, 2015), patients with type 2 diabetes without psoriasis or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011), and age- and sex-matched healthy controls without psoriasis, type 2 diabetes, or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011). Exposures: Psoriasis, type 2 diabetes, and healthy control effect on coronary artery calcium score. Main Outcomes and Measures: Coronary artery calcium measured by Agatston score. Results: A total of 387 individuals participated in the study. Mean (SD) age was 51 (7.7), 52 (8.0), and 52 (8.0) years in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively. There were 64 men (49.6%) in each group, and most patients were white (119 [92.2%], 123 [95.3%], and 128 [99.2%] in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively). Patients with psoriasis had low cardiovascular risk measured by the Framingham Risk Score but had a high prevalence of cardiovascular and cardiometabolic risk factors, similar to patients with type 2 diabetes. In a fully adjusted model, psoriasis was associated with coronary artery calcium (Tobit regression ratio, 0.89; P < .001) similar to the association in type 2 diabetes (Tobit regression ratio, 0.79; P = .04). Likelihood ratio testing revealed incremental value for psoriasis in a fully adjusted model (chi2 = 4.48, P = .03) in predicting coronary artery calcium. Psoriasis was independently associated with the presence of any coronary artery calcium (odds ratio, 2.35; 95% CI, 1.12-4.94) in fully adjusted models, whereas the association of coronary artery calcium with type 2 diabetes was no longer significant after adding body mass index to the model (odds ratio, 2.18; 95% CI, 0.75-6.35). Conclusions and Relevance: Patients with psoriasis have increased coronary artery calcium by mean total Agatston scores, similar to that of patients with type 2 diabetes, suggesting that patients with psoriasis harbor high rates of subclinical atherosclerosis beyond adjustment for body mass index. Major educational efforts for patients and physicians should be undertaken to reduce the burden of cardiovascular disease in patients with psoriasis. PMID- 27556411 TI - Insights on the Auxochromic Properties of the Guanidinium Group. AB - UV/vis spectra of phenylguanidine (PHGU) in the gas phase and in acetonitrile have been simulated by TD-DFT calculations. Several DFT hybrid and long-range corrected functionals were tested with respect to CASPT2 gas phase calculations. Solvent effects were considered using polarizable continuum model (PCM) and compared with the measured data in acetonitrile. Comparison with isoelectronic phenylurea and related phenyltiourea was done as well. The PBE0 and long-range corrected CAM-B3LYP functionals were selected to investigate the effect of protonation on the excitation energies and absorption intensities of PHGU and several guanidine derivatives with different aromatic chromophoric groups (naphthyl, anthracenyl, quinolinyl, anthraquinonyl, and coumarinyl). Also, the effect of complexation and specific interactions through hydrogen bonds with different anions was examined. It was shown that the protonation of the guanidine subunit shifts the low energy absorption bands toward higher energies (hypsochromic shift). The shift is reduced upon complexation with anions. In phenylguanidine salts, lambdamax values are correlated to the anion basicity and strength of H-bonding. The observed changes diminish upon increase of chromophoric size (naphthyl, anthracenyl). Theoretical predictions of UV/vis spectra correlate well with experimentally measured spectra of selected guanidine derivatives and their salts. PMID- 27556412 TI - Atypical Antipsychotic-Induced Weight Gain in Children and Adolescents: Sometimes Less Is More. PMID- 27556413 TI - Surgical Management of Choledocholithiasis: A Disappearing Skill. PMID- 27556414 TI - New Insights into the Structure Changes and Interface Properties of Li3VO4 Anode for Lithium-Ion Batteries during the Initial Cycle by in-Situ Techniques. AB - Li3VO4 has been regarded as a new-type anode of lithium-ion batteries in recent years, which has a high theoretical specific capacity of 394 mAh g(-1), a proper potential for Li(+) insertion/deinsertion (~1 V), and a good rate capacity. However, its low initial Coulombic efficiency, poor conductivity, and poor cycle performance restricts its development. In order to figure out the cause of the low initial Coulombic efficiency of Li3VO4 material, the nanosized Li3VO4 material was synthesized by citric acid-assisted sol-gel method. The lithium storage behaviors of the prepared Li3VO4 material were studied by in-situ XRD and in-situ EIS techniques. In-situ XRD results indicated that there was irreversible phase transformation of Li3VO4 during the initial charging/discharging process. In-situ EIS experiment was performed during the potentiostatic intermittent titration technique (PITT) process to discuss the formation of the solid electrolyte interface (SEI) on the Li3VO4 and the kinetics of lithium-ion diffusion. It is worth pointing out that this is the first time to prove the existence of SEI on Li3VO4 during the initial charging/discharging process by in situ EIS experiment. It turned out that the irreversible phase transformation and the formation of SEI on Li3VO4 were the two important reasons causing the low initial Coulombic efficiency of Li3VO4 material. PMID- 27556415 TI - Biogenic Fenton-like Reaction Involvement in Cometabolic Degradation of Tetrabromobisphenol A by Pseudomonas sp. fz. AB - Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant (BFR) that has frequently been detected in various environmental compartments. Although TBBPA biotransformation has been observed under both aerobic and anaerobic conditions, knowledge of the detailed mechanism of direct aerobic TBBPA biodegradation still remains limited. In this study, the underlying mechanism of cometabolic degradation of TBBPA by Pseudomonas sp. fz under aerobic conditions was investigated. Two key degradation pathways (beta scission and debromination) were proposed based on triple quadrupole liquid chromatography-mass spectrometry (LC-MS) analysis. TBBPA degradation by strain fz was demonstrated to be an extracellular process associated with the low-molecular-mass component (LMMC). Moreover, LMMC was preliminarily identified as oligopeptides, mainly consisting of glycine, proline, and alanine in a 2:1:1 molar ratio. Quenching studies suggested the involvement of hydroxyl radicals ((*)OH) in extracellular TBBPA degradation. To the best of our knowledge, we provide the first evidence that TBBPA was degraded by a biogenic Fenton-like reaction mediated via extracellular H2O2 and Fe(II)-oligopeptide complexes by the genus Pseudomonas. This study provides a new insight into the fate and biodegradation of TBBPA and other organic pollutants in natural and artificial bioremediation environments. PMID- 27556416 TI - A matrix rank based concordance index for evaluating and detecting conditional specific co-expressed gene modules. AB - BACKGROUND: Gene co-expression network analysis (GCNA) is widely adopted in bioinformatics and biomedical research with applications such as gene function prediction, protein-protein interaction inference, disease markers identification, and copy number variance discovery. Currently there is a lack of rigorous analysis on the mathematical condition for which the co-expressed gene module should satisfy. METHODS: In this paper, we present a linear algebraic based Centralized Concordance Index (CCI) for evaluating the concordance of co expressed gene modules from gene co-expression network analysis. The CCI can be used to evaluate the performance for co-expression network analysis algorithms as well as for detecting condition specific co-expression modules. We applied CCI in detecting lung tumor specific gene modules. RESULTS AND DISCUSSION: Simulation showed that CCI is a robust indicator for evaluating the concordance of a group of co-expressed genes. The application to lung cancer datasets revealed interesting potential tumor specific genetic alterations including CNVs and even hints for gene-fusion. Deeper analysis required for understanding the molecular mechanisms of all such condition specific co-expression relationships. CONCLUSION: The CCI can be used to evaluate the performance for co-expression network analysis algorithms as well as for detecting condition specific co expression modules. It is shown to be more robust to outliers and interfering modules than density based on Pearson correlation coefficients. PMID- 27556417 TI - Improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies. AB - BACKGROUND: Ion Torrent and Ion Proton are semiconductor-based sequencing technologies that feature rapid sequencing speed and low upfront and operating costs, thanks to the avoidance of modified nucleotides and optical measurements. Despite of these advantages, however, Ion semiconductor sequencing technologies suffer much reduced sequencing accuracy at the genomic loci with homopolymer repeats of the same nucleotide. Such limitation significantly reduces its efficiency for the biological applications aiming at accurately identifying various genetic variants. RESULTS: In this study, we propose a Bayesian inference based method that takes the advantage of the signal distributions of the electrical voltages that are measured for all the homopolymers of a fixed length. By cross-referencing the length of homopolymers in the reference genome and the voltage signal distribution derived from the experiment, the proposed integrated model significantly improves the alignment accuracy around the homopolymer regions. CONCLUSIONS: Besides improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies with the proposed model, similar strategies can also be used on other high-throughput sequencing technologies that share similar limitations. PMID- 27556418 TI - Reconstructing directed gene regulatory network by only gene expression data. AB - BACKGROUND: Accurately identifying gene regulatory network is an important task in understanding in vivo biological activities. The inference of such networks is often accomplished through the use of gene expression data. Many methods have been developed to evaluate gene expression dependencies between transcription factor and its target genes, and some methods also eliminate transitive interactions. The regulatory (or edge) direction is undetermined if the target gene is also a transcription factor. Some methods predict the regulatory directions in the gene regulatory networks by locating the eQTL single nucleotide polymorphism, or by observing the gene expression changes when knocking out/down the candidate transcript factors; regrettably, these additional data are usually unavailable, especially for the samples deriving from human tissues. RESULTS: In this study, we propose the Context Based Dependency Network (CBDN), a method that is able to infer gene regulatory networks with the regulatory directions from gene expression data only. To determine the regulatory direction, CBDN computes the influence of source to target by evaluating the magnitude changes of expression dependencies between the target gene and the others with conditioning on the source gene. CBDN extends the data processing inequality by involving the dependency direction to distinguish between direct and transitive relationship between genes. We also define two types of important regulators which can influence a majority of the genes in the network directly or indirectly. CBDN can detect both of these two types of important regulators by averaging the influence functions of candidate regulator to the other genes. In our experiments with simulated and real data, even with the regulatory direction taken into account, CBDN outperforms the state-of-the-art approaches for inferring gene regulatory network. CBDN identifies the important regulators in the predicted network: 1. TYROBP influences a batch of genes that are related to Alzheimer's disease; 2. ZNF329 and RB1 significantly regulate those 'mesenchymal' gene expression signature genes for brain tumors. CONCLUSION: By merely leveraging gene expression data, CBDN can efficiently infer the existence of gene-gene interactions as well as their regulatory directions. The constructed networks are helpful in the identification of important regulators for complex diseases. PMID- 27556420 TI - Adaptation and Compensation of Vestibular Responses Following Superior Canal Dehiscence Surgery. AB - OBJECTIVE: To describe vestibulo-ocular function and compensatory mechanisms in the immediate postoperative period after superior canal dehiscence surgery. STUDY DESIGN: Prospective longitudinal study. SETTING: Tertiary medical center. PATIENTS: Five patients who underwent plugging of superior semicircular canal via middle cranial fossa approach. INTERVENTIONS: Bedside quantitative video head impulse testing (vHIT). MAIN OUTCOME MEASURES: Dynamic measures of vestibulo ocular reflex (VOR) function including VOR gain and compensatory saccades during vHIT. RESULTS: Mean VOR gain of the ipsilateral superior semicircular canal (SC) decreased from 0.71 +/- 0.1 preoperatively to 0.28 +/- 0.07 on postoperative day (POD) 2-4 (p = 0.0031), consistent with plugging. There was also a significant immediate postoperative decrease of VOR gain for the other ipsilateral canals (posterior canal (PC) from gain 0.91 +/- 0.33 down to 0.55 +/- 0.14, p = 0.040; horizontal canal (HC) from 0.81 +/- 0.08 down to 0.54 +/- 0.19, p = 0.038). On PODs 1-2, compensatory saccades after testing the plugged SC occurred exclusively after the head stopped moving (overt) with latency of 186.2 ms +/- 19.9 ms. By POD 7 saccade latency decreased to 141.0 +/- 17.5 ms (p = 0.032), and saccades were occurring during the vertical head rotation (covert saccades). Follow-up >40 days was consistent with previous findings in that mean SC gain remained low. HC gain recovered fully, but some cases did not have full recovery of PC gain. CONCLUSION: When the SC is plugged surgically, early quantitative vHIT demonstrates significantly reduced VOR gain for all of the ipsilateral canals. Possible mechanisms include labyrinthine inflammation and loss of perilymph at the time of surgery. Full recovery is typical for the horizontal canal but not always for the PC. Evidence of central compensation occurred by the elicitation of compensatory saccades and by reducing their latencies within the first week after surgery. PMID- 27556419 TI - CrossLink: a novel method for cross-condition classification of cancer subtypes. AB - BACKGROUND: We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another. METHODS: To address the problem of current normalization approaches, we propose a novel algorithm called CrossLink (CL). CL recognizes that there is no universal, condition-independent normalization mapping of signatures. In contrast, it exploits the fact that the signature is unique to its associated class under any condition and thus employs an unsupervised clustering algorithm to discover this unique signature. RESULTS: We assessed the performance of CL for cross-condition predictions of PAM50 subtypes of breast cancer by using a simulated dataset modeled after TCGA BRCA tumor samples with a cross-validation scheme, and datasets with known and unknown PAM50 classification. CL achieved prediction accuracy >73 %, highest among other methods we evaluated. We also applied the algorithm to a set of breast cancer tumors derived from Arabic population to assign a PAM50 classification to each tumor based on their gene expression profiles. CONCLUSIONS: A novel algorithm CrossLink for cross-condition prediction of cancer classes was proposed. In all test datasets, CL showed robust and consistent improvement in prediction performance over other state-of-the-art normalization and classification algorithms. PMID- 27556421 TI - Determinants of using (non-)fluoroscopy-guided positioning for radiographs: a case study research. AB - This study examines the determinants of using (non-)fluoroscopy-guided positioning (FGP) for radiographs, in order to improve the use of non-FGP imaging techniques. We focused on knowledge and attitudes of radiographers and radiologists with respect to applying non-FGP in radiography and organizational factors. We analyzed data from an in-depth multiple case study that includes observations and field notes, interviews, documents and images collected from the radiology departments of four hospitals. The unified theory of acceptance and use of technology (UTAUT) was used to frame the findings. We found that inadequate skills and insufficient knowledge of positioning techniques and negative attitudes towards non-FGP were present. More precisely, staff expressed concerns with respect to the impact on the workload and workflow. Besides facilitating organizational conditions, the social influence of peers and the clinical leadership of RLs were found to be important. Adequate supervision, regular feedback and coaching were identified as important enabling factors for increasing the quality of the applied imaging techniques. In the conclusion we state that determinants of using non-FGP are quite complex. Therefore we argue that a holistic approach considering all these aspects is needed to improve imaging practices. PMID- 27556422 TI - Dosimetric predictors of acute haematological toxicity in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy. AB - OBJECTIVE: Haematological toxicity (HT) is common in patients with oesophageal cancer (EC) treated with chemoradiotherapy (CRT). The Quantitative Analysis of Normal Tissue Effects in the Clinic guidelines provide no dose constraints for the bone marrow (BM) to avoid HT. We aimed to determine dosimetric factors associated with HT during CRT for EC. METHODS: 41 patients with EC treated with neoadjuvant cisplatin and 5-fluorouracil-based CRT were retrospectively reviewed. Associations between the dose-volume histogram parameters of thoracic bones and blood cell count changes during CRT were assessed using logistic regression analyses. Receiver-operating characteristic curves were used to derive optimal dosimetric planning constraints. Vx indicates the total organ volume percentage exceeding a radiation dose of x (Gy). RESULTS: Greater thoracic vertebrae and rib irradiation doses, including mean vertebral dose (MVD), thoracic vertebrae V5-30 (TVV5-30), mean rib dose and rib V5-20, were associated with increased leukopenia (grade >= 3) risk. Additional BM sites (sternum, scapulae and clavicles) did not influence HT. White blood cell and absolute neutrophil count nadirs were associated with increased irradiation doses to the thoracic vertebrae, ribs and sternum. Chemotherapy cycle number was not significantly associated with severe neutropenia or leukopenia. Cut-off values with the highest likelihood of avoiding leukopenia were MVD < 25.9 Gy, TVV20 < 70% and TVV10 < 77%. CONCLUSION: Thoracic bone irradiation dose was significantly associated with HT after adjusting for chemotherapy effects. Efforts to maintain MVD < 25.9 Gy, TVV10 < 77% and TVV20 < 70% could reduce HT. ADVANCES IN KNOWLEDGE: This is the first study addressing issues concerning HT in patients with neoadjuvant CRT-treated EC. PMID- 27556423 TI - Direct Evidence for Metabolon Formation and Substrate Channeling in Recombinant TCA Cycle Enzymes. AB - Supramolecular assembly of enzymes into metabolon structures is thought to enable efficient transport of reactants between active sites via substrate channeling. Recombinant versions of porcine citrate synthase (CS), mitochondrial malate dehydrogenase (mMDH), and aconitase (Aco) were found to adopt a homogeneous native-like metabolon structure in vitro. Site-directed mutagenesis performed on highly conserved arginine residues located in the positively charged channel connecting mMDH and CS active sites led to the identification of CS(R65A) which retained high catalytic efficiency. Substrate channeling between the CS mutant and mMDH was severely impaired and the overall channeling probability decreased from 0.99 to 0.023. This work provides direct mechanistic evidence for the channeling of reaction intermediates, and disruption of this interaction would have important implications on the control of flux in central carbon metabolism. PMID- 27556424 TI - Self-Sampling as an Intervention to Promote Cervical Cancer Screening Among Women With HIV. PMID- 27556425 TI - MoS2 Nanosheets Vertically Grown on Graphene Sheets for Lithium-Ion Battery Anodes. AB - A designed nanostructure with MoS2 nanosheets (NSs) perpendicularly grown on graphene sheets (MoS2/G) is achieved by a facile and scalable hydrothermal method, which involves adsorption of Mo7O24(6-) on a graphene oxide (GO) surface, due to the electrostatic attraction, followed by in situ growth of MoS2. These results give an explicit proof that the presence of oxygen-containing groups and pH of the solution are crucial factors enabling formation of a lamellar structure with MoS2 NSs uniformly decorated on graphene sheets. The direct coupling of edge Mo of MoS2 with the oxygen from functional groups on GO (C-O-Mo bond) is proposed. The interfacial interaction of the C-O-Mo bonds can enhance electron transport rate and structural stability of the MoS2/G electrode, which is beneficial for the improvement of rate performance and long cycle life. The graphene sheets improve the electrical conductivity of the composite and, at the same time, act not only as a substrate to disperse active MoS2 NSs homogeneously but also as a buffer to accommodate the volume changes during cycling. As an anode material for lithium-ion batteries, the manufactured MoS2/G electrode manifests a stable cycling performance (1077 mAh g(-1) at 100 mA g(-1) after 150 cycles), excellent rate capability, and a long cycle life (907 mAh g(-1) at 1000 mA g(-1) after 400 cycles). PMID- 27556426 TI - [Not Available]. PMID- 27556427 TI - [Technique of Mesohepatectomy]. AB - In patients with primary or secondary malignant central liver tumours, the standard surgical procedure is extended left or right hemihepatectomy. Since extended resections are associated with increased morbidity and mortality and a loss of a large amount of functional liver parenchyma, central liver resection or mesohepatectomy (resection of segments 4a/4b, 5 and 8) with or without the resection of segment 1 is an alternative procedure, although technically demanding and not widely used so far. Resection margins are to the right of the falciform ligament and at the border between segments 5/6 and 7/8, which can be difficult to differentiate. Intraoperative sonography is highly recommended. The current video shows the technique of mesohepatectomy under exclusion of segment 1 in a case of a central colorectal liver metastasis. PMID- 27556428 TI - [Surgical Oncology, Metastatic Disease]. PMID- 27556429 TI - [The Impact of Tumor Cell Proliferation on Occult Micrometastases, Tumor Recurrence and Patient Outcome Following Resection for Liver Malignancies]. AB - Liver resection is currently considered to be essential part of the curative treatment of primary and secondary liver malignancies. However, long-term survival in these patients is limited by the high incidence of tumor recurrence. Recent clinical and experimental studies have indicated that cellular and molecular mechanisms associated with liver regeneration after partial hepatectomy may have a proliferative effect on occult micrometastases and circulating tumor cells and are thus responsible for recurrent disease. Growth factors and cytokines involved in liver regeneration have also been shown to influence tumour growth and metastasis. However, the underlying mechanisms explaining the interactions between regenerating liver tissue and tumour cell proliferation remain unclear. The development of modern agents specifically targeting these processes may improve disease-free and overall survival rates after oncological hepatectomy. PMID- 27556430 TI - Four New Dicaffeoylquinic Acid Derivatives from Glasswort (Salicornia herbacea L.) and Their Antioxidative Activity. AB - Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5 dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, and 3,5-di-dihydrocaffeoylquinic acid methyl ester. Their chemical structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy (LC-ESI-MS). In addition, the presence of dicaffeoylquinic acid derivatives in this plant was reconfirmed by LC-ESI-MS/MS analysis. The isolated compounds strongly scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited cholesteryl ester hydroperoxide formation during rat blood plasma oxidation induced by copper ions. These results indicate that the caffeoylquinic acid derivatives may partially contribute to the antioxidative effect of S. herbacea. PMID- 27556431 TI - Optimization of the Ultrasonic-Assisted Extraction of Bioactive Flavonoids from Ampelopsis grossedentata and Subsequent Separation and Purification of Two Flavonoid Aglycones by High-Speed Counter-Current Chromatography. AB - The fermented leaf of Ampelopsis grossedentata has been used as a beverage and folk medicine called "vine tea" in the southern region of China. In this paper, the optimum extraction conditions for the maximum recovery amounts of total flavonoids (TF), dihydromyricetin (DMY), myricitrin (MYG) and myricetin (MY) from natural Ampelopsis grossedentata leaves subjected to ultrasonic-assisted extraction (UAE) were determined and optimized by using response surface methodology. The method was employed by the Box-Behnken design (BBD) and Derringer's desirability function using methanol concentration, extraction time, liquid/solid ratio as factors and the contents of TF, DMY, MYG and MY as responses. The obtained optimum UAE conditions were as follows: a solvent of 80.87% methanol, an extraction time of 31.98 min and a liquid/solid ratio of 41.64:1 mL/g. Through analysis of the response surface, it implied that methanol concentration and the liquid/solid ratio had significant effects on TF, DMY, MYG and MY yields, whereas extraction time had relatively little effects. The established extraction and analytical methods were successfully applied to determine the contents of the total flavonoids and three individual flavonoids in 10 batches of the leaf samples of A. grossedentata from three counties in Fujian Province, China. The results suggested the variability in the quality of A. grossedentata leaves from different origins. In addition, high purities of dihydromyricetin and myricetin were simultaneously separated and purified from the extract subjected to optimized UAE, by high-speed counter-current chromatography using a solvent system of N-hexane-ethyl acetate-methanol-water (1:3:2:4; v/v/v/v). In a single operation, 200 mg of the extract were separated to yield 86.46 mg of dihydromyricetin and 3.61 mg of myricetin with the purity of 95.03% and 99.21%, respectively. The results would be beneficial for further exploiting the herbal products and controlling the quality of the herb and its derived products. PMID- 27556432 TI - Copper Ion Attenuated the Antiproliferative Activity of Di-2-pyridylhydrazone Dithiocarbamate Derivative; However, There Was a Lack of Correlation between ROS Generation and Antiproliferative Activity. AB - The use of chelators for cancer treatment has been an alternative option. Dithiocarbamates have recently attracted considerable attention owning to their diverse biological activities; thus, the preparation of new dithiocarbamate derivatives with improved antitumor activity and selectivity as well as probing the underlying molecular mechanism are required. In this study, di-2 pyridylhydrazone dithiocarbamate S-propionic acid (DpdtpA) and its copper complex were prepared and characterized, and its antiproliferative activity was evaluated. The proliferation inhibition assay showed that DpdtpA exhibited excellent antiproliferative effect in hepatocellular carcinoma (IC50 = 1.3 +/- 0.3 MUM for HepG2, and 2.5 +/- 0.6 MUM for Bel-7402). However, in the presence of copper ion, the antiproliferative activity of DpdtpA was dramatically attenuated (20-30 fold) owing to the formation of copper chelate. A preliminarily mechanistic study revealed that reactive oxygen species (ROS) generation mediated the antiproliferative activity of DpdtpA, and accordingly induced apoptosis, DNA cleavage, and autophagy. Surprisingly, the cytotoxicity of DpdtpA copper complex (DpdtpA-Cu) was also involved in ROS generation; however, a paradoxical relation between cellular ROS level and cytotoxicity was observed. Further investigation indicated that DpdtpA could induce cell cycle arrest at the S phase; however, DpdtpA-Cu lacked this effect, which explained the difference in their antiproliferative activity. PMID- 27556433 TI - Effect of Mono- and Poly-CH/P Exchange(s) on the Aromaticity of the Tropylium Ion. AB - In view of the fact that the phosphorus atom in its low co-ordination state (coordination numbers 1 and 2) has been termed as the carbon copy, there have been attempts to investigate, theoretically as well as experimentally, the effect of the exchange(s) of CH- moiety with phosphorus atom(s) (CH/P) on the structural and other aspects of the classical carbocyclic and heterocyclic systems. Tropylium ion is a well-known non-benzenoid aromatic system and has been studied extensively for its aromatic character. We have now investigated the effect of mono- and poly-CH/P exchange(s) on the aromaticity of the tropylium ion. For this purpose, the parameters based on the geometry and magnetic properties, namely bond equalization, aromatic stabilization energies (ASE), Nucleus-Independent Chemical Shift (NICS) values, (NICS(0), NICS(1), NICS(1)zz), proton nucleus magnetic resonance (1H-NMR) chemical shifts, magnetic susceptibility exaltation and magnetic anisotropic values of mono-, di-, tri- and tetra-phosphatropylium ions have been determined at the Density Functional Theory (DFT) (B3LYP/6 31+G(d)) level. Geometry optimization reveals bond length equalization. ASEs range from -46.3 kcal/mol to -6.2 kcal/mol in mono- and diphospha-analogues which are planar. However, the ions having three and four phosphorus atoms lose planarity and their ASE values approach the values typical for non-aromatic structures. Of the three NICS values, the NICS(1)zz is consistently negative showing aromatic character of all the systems studied. It is also supported by the magnetic susceptibility exaltations and magnetic anisotropic values. Furthermore, 1H-NMR chemical shifts also fall in the aromatic region. The conclusion that mono-, di-, tri- and tetra-phosphatropylium ions are aromatic in nature has been further corroborated by determining the energy gap between the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) (HOMO - LUMO gap), which falls in the range, ca. 3 * 10(-19)-9 * 10(-19) J. The systems having more than four phosphorus atoms are not able to sustain their monocyclic structure. PMID- 27556434 TI - Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation. AB - Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation. PMID- 27556435 TI - Self-Supported N-Heterocyclic Carbenes and Their Use as Organocatalysts. AB - The study of N-heterocyclic carbenes (NHCs) as organocatalysts has proliferated in recent years, and they have been found to be useful in a variety of reactions. In an attempt to further expand their utility and to study their recyclability, we designed and synthesized a series of self-supported NHCs in which the catalytic carbene groups form part of a densely functionalized polymer backbone, and studied them as organocatalysts. Of the self-Supported NHCs examined, a benzimidazole derived polymer with flexible linkers connecting the catalytic groups was found to be the most efficient organocatalyst in a model benzoin condensation reaction, and thus it was used in a variety of such reactions, including some involving catalyst recycling. Furthermore, it was also used to catalyze a set of redox esterification reactions involving conjugated unsaturated aldehydes. In all of these reactions the catalyst afforded good yield of the desired product and its polymeric nature facilitated product purification. PMID- 27556436 TI - Gold Nanocluster Decorated Polypeptide/DNA Complexes for NIR Light and Redox Dual Responsive Gene Transfection. AB - Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection. PMID- 27556437 TI - Neuroprotective Effects of Methyl 3,4-Dihydroxybenzoate against TBHP-Induced Oxidative Damage in SH-SY5Y Cells. AB - This study investigated the neuroprotective effects of methyl 3,4 dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB or N-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 MUM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2',7' dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8 OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells. PMID- 27556438 TI - Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en 1-one in Mice Models of Induced Nociception. AB - The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system. PMID- 27556439 TI - Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway. AB - Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications. PMID- 27556440 TI - Punica granatum L. Hydrogel for Wound Care Treatment: From Case Study to Phytomedicine Standardization. AB - The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the effect produced by a magistral formulation of ethanolic extracts of Punica granatum peels on a non-healing chronic ulcer. The complete closure of the chronic ulcer that was initially not responsive to standard medical care was observed. A 2% (w/w) P. granatum peels ethanolic extract hydrogel-based formulation (PGHF) was standardized and subjected to physicochemical studies to establish the quality control parameters using, among others, assessment criteria such as optimum appearance, pH range, viscosity and hydrogel disintegration. The stability and quantitative chromatographic data was assessed in storage for six months under two temperature regimes. An efficient HPLC-DAD method was established distinguishing the biomarkers punicalin and punicalagin simultaneously in a single 8 min run. PGHF presented suitable sensorial and physicochemical performance, showing that punicalagin was not significantly affected by storage (p > 0.05). Formulations containing extracts with not less than 0.49% (w/w) total punicalagin might find good use in wound healing therapy. PMID- 27556441 TI - Effect of the Production of Dried Fruits and Juice from Chokeberry (Aronia melanocarpa L.) on the Content and Antioxidative Activity of Bioactive Compounds. AB - The aim of this study was to evaluate the production of dried fruits and juices from chokeberry as potential sources of bioactive compounds with beneficial effects on human health. Dry powders and juices from chokeberry were analyzed for the contents of sugars with high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC-ELSD method), and the antioxidant capacity was analyzed by the FRAP (ferric-reducing ability of plasma) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) tests. Polyphenols were identified by high performance liquid chromatography (HPLC) coupled with a tandem mass spectrometer and a photodiode-array detector (LC-PDA-ESI-MS/MS), and their quantitative analysis was carried out by UPLC-MS/MS (using a Q/TOF detector and a PDA detector). A total of 27 polyphenolic compounds was identified in chokeberry products, including 7 anthocyanins, 11 flavonols, 5 phenolic acids, 3 flavan-3 ols and 1 flavanone. Three anthocyanin derivatives were reported for the first time from chokeberry fruit. A higher activity of the bioactive compounds was determined in dried fruit pomace and in juice obtained from crushed fruits than in those from the whole fruits. In addition, the pomace was found to be a better material for the production of dry powders, compared to chokeberry fruits. PMID- 27556442 TI - A Novel Insecticidal Peptide SLP1 Produced by Streptomyces laindensis H008 against Lipaphis erysimi. AB - Aphids are major insect pests for crops, causing damage by direct feeding and transmission of plant diseases. This paper was completed to discover and characterize a novel insecticidal metabolite against aphids from soil actinobacteria. An insecticidal activity assay was used to screen 180 bacterial strains from soil samples against mustard aphid, Lipaphis erysimi. The bacterial strain H008 showed the strongest activity, and it was identified by the phylogenetic analysis of the 16S rRNA gene and physiological traits as a novel species of genus Streptomyces (named S. laindensis H008). With the bioassay guided method, the insecticidal extract from S. laindensis H008 was subjected to chromatographic separations. Finally, a novel insecticidal peptide was purified from Streptomyces laindensis H008 against L. erysimi, and it was determined to be S-E-P-A-Q-I-V-I-V-D-G-V-D-Y-W by TOF-MS and amino acid analysis. PMID- 27556443 TI - Ribosome Inactivating Proteins from Rosaceae. AB - Ribosome-inactivating proteins (RIPs) are widespread among higher plants of different taxonomic orders. In this study, we report on the RIP sequences found in the genome/transcriptome of several important Rosaceae species, including many economically important edible fruits such as apple, pear, peach, apricot, and strawberry. All RIP domains from Rosaceae share high sequence similarity with conserved residues in the catalytic site and the carbohydrate binding sites. The genomes of Malus domestica and Pyrus communis contain both type 1 and type 2 RIP sequences, whereas for Prunus mume, Prunus persica, Pyrus bretschneideri, and Pyrus communis a complex set of type 1 RIP sequences was retrieved. Heterologous expression and purification of the type 1 as well as the type 2 RIP from apple allowed to characterize the biological activity of the proteins. Both RIPs from Malus domestica can inhibit protein synthesis. Furthermore, molecular modelling suggests that RIPs from Rosaceae possess three-dimensional structures that are highly similar to the model proteins and can bind to RIP substrates. Screening of the recombinant type 2 RIP from apple on a glycan array revealed that this type 2 RIP interacts with terminal sialic acid residues. Our data suggest that the RIPs from Rosaceae are biologically active proteins. PMID- 27556444 TI - Furfural Production from d-Xylose and Xylan by Using Stable Nafion NR50 and NaCl in a Microwave-Assisted Biphasic Reaction. AB - Pentose dehydration and direct transformation of xylan into furfural were performed in a water-cyclopentyl methyl ether (CPME) biphasic system under microwave irradiation. Heated up between 170 and 190 degrees C in the presence of Nafion NR50 and NaCl, d-xylose, l-arabinose and xylan gave furfural with maximum yields of 80%, 42% and 55%, respectively. The influence of temperature and reaction time on the reaction kinetics was discussed. This study was also completed by the survey of different reactant ratios, such as organic layer-water or catalyst-inorganic salt ratios. The exchange between proton and cation induced by an excess of NaCl was monitored, and a synergetic effect between the remaining protons and the released HCl was also discovered. PMID- 27556445 TI - Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats. AB - Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL. PMID- 27556446 TI - TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto's Thyroiditis. AB - The aim of the current study was to examine whether the polymorphism loci of the tumor necrosis factor superfamily member 4 (TNFSF4) gene increase the risk of susceptibility to autoimmune thyroid diseases (AITDs) in the Han Chinese population, and a case-control study was performed in a set of 1,048 AITDs patients and 909 normal healthy controls in the study. A total of four tagging single nucleotide polymorphisms (SNPs) in the TNFSF4 region, including rs7514229, rs1234313, rs16845607 and rs3850641, were genotyped using the method of ligase detection reaction. An association between GG genotype of rs3850641 in TNFSF4 gene and AITDs was found (p = 0.046). Additionally, the clinical sub-phenotype analysis revealed a significant association between GG genotype in rs7514229 and AITDs patients who were <=18 years of age. Furthermore, rs3850641 variant allele G was in strong association with hypothyroidism in Hashimoto's thyroiditis (HT) (p = 0.018). The polymorphisms of the TNFSF4 gene may contribute to the susceptibility to AITDs pathogenesis. PMID- 27556447 TI - Inhibitory Effect of 2,3,5,6-Tetrafluoro-4-[4-(aryl)-1H-1,2,3-triazol-1 yl]benzenesulfonamide Derivatives on HIV Reverse Transcriptase Associated RNase H Activities. AB - The HIV-1 ribonuclease H (RNase H) function of the reverse transcriptase (RT) enzyme catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate, and represents a suitable target for drug development. A particularly attractive approach is constituted by the interference with the RNase H metal-dependent catalytic activity, which resides in the active site located at the C-terminus p66 subunit of RT. Herein, we report results of an in-house screening campaign that allowed us to identify 4-[4-(aryl) 1H-1,2,3-triazol-1-yl]benzenesulfonamides, prepared by the "click chemistry" approach, as novel potential HIV-1 RNase H inhibitors. Three compounds (9d, 10c, and 10d) demonstrated a selective inhibitory activity against the HIV-1 RNase H enzyme at micromolar concentrations. Drug-likeness, predicted by the calculation of a panel of physicochemical and ADME properties, putative binding modes for the active compounds, assessed by computational molecular docking, as well as a mechanistic hypothesis for this novel chemotype are reported. PMID- 27556448 TI - MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes. AB - Ossification of the ligamentum flavum (OLF) is a disorder of heterotopic ossification of spinal ligaments and is the main cause of thoracic spinal canal stenosis. Previous studies suggested that miR-132-3p negatively regulates osteoblast differentiation. However, whether miR-132-3p is involved in the process of OLF has not been investigated. In this study, we investigated the effect of miR-132-3p and its target genes forkhead box O1 (FOXO1), growth differentiation factor 5 (GDF5) and SRY-box 6 (SOX6) on the osteogenic differentiation of ligamentum flavum (LF) cells. We demonstrated that miR-132-3p was down-regulated during the osteogenic differentiation of LF cells and negatively regulated the osteoblast differentiation. Further, miR-132-3p targeted FOXO1, GDF5 and SOX6 and down-regulated the protein expression of these genes. Meanwhile, FOXO1, GDF5 and SOX6 were up-regulated after osteogenic differentiation and the down-regulation of endogenous FOXO1, GDF5 or SOX6 suppressed the osteogenic differentiation of LF cells. In addition, we also found FOXO1, GDF5 and SOX6 expression in the ossification front of OLF samples. Overall, these results suggest that miR-132-3p inhibits the osteogenic differentiation of LF cells by targeting FOXO1, GDF5 and SOX6. PMID- 27556449 TI - How Many Conformations of Enzymes Should Be Sampled for DFT/MM Calculations? A Case Study of Fluoroacetate Dehalogenase. AB - The quantum mechanics/molecular mechanics (QM/MM) method (e.g., density functional theory (DFT)/MM) is important in elucidating enzymatic mechanisms. It is indispensable to study "multiple" conformations of enzymes to get unbiased energetic and structural results. One challenging problem, however, is to determine the minimum number of conformations for DFT/MM calculations. Here, we propose two convergence criteria, namely the Boltzmann-weighted average barrier and the disproportionate effect, to tentatively address this issue. The criteria were tested by defluorination reaction catalyzed by fluoroacetate dehalogenase. The results suggest that at least 20 conformations of enzymatic residues are required for convergence using DFT/MM calculations. We also tested the correlation of energy barriers between small QM regions and big QM regions. A roughly positive correlation was found. This kind of correlation has not been reported in the literature. The correlation inspires us to propose a protocol for more efficient sampling. This saves 50% of the computational cost in our current case. PMID- 27556450 TI - Protection of Historical Wood against Microbial Degradation-Selection and Application of Microbiocides. AB - The aim of this study was to select effective and safe microbiocides for the disinfection and protection of historical wooden surfaces at the former Auschwitz II-Birkenau concentration and extermination camp. We tested seven active compounds against bacteria and moulds, of which didecyldimethylammonium chloride and N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine were effective even at 0.02% 2%. Subsequently, eight microbiocides containing the selected active ingredients were chosen and applied three times on the surface of wood samples colonized by bacteria and moulds. ABM-1 and ABM-2-6% solution; Rocima 101-8%; Preventol R 80 12%; Acticide 706 LV-15% and Boramon-30% were the most effective disinfectants. Under laboratory conditions, ABM-1, Boramon and Rocima 101 ensured antimicrobial protection of new wood samples for six months. In situ, 30% Boramon and 8% Rocima 101 applied by spraying effectively protected the historical wood from bacterial and mould growth for 12 and 3 months, respectively. Colour and luminance of the new wood were not altered after exposure to the biocides. Boramon and Rocima 101, applied by the spraying method, caused no significant change in the colour of the historical wood. Results from this study were used to develop a procedure for the protection of wood in historical buildings against biodeterioration. PMID- 27556451 TI - Syngonanthus nitens Bong. (Rhul.)-Loaded Nanostructured System for Vulvovaginal Candidiasis Treatment. AB - Herbal-loaded drug delivery nanotechnological systems have been extensively studied recently. The antimicrobial activity of medicinal plants has shown better pharmacological action when such plants are loaded into a drug delivery system than when they are not loaded. Syngonanthus nitens Bong. (Rhul.) belongs to the Eriocaulaceae family and presents antiulcerogenic, antioxidant, antibacterial, and antifungal activity. The aim of this study was to evaluate the antifungal activity of Syngonanthus nitens (S. nitens) extract that was not loaded (E) or loaded (SE) into a liquid crystal precursor system (S) for the treatment of vulvovaginal candidiasis (VVC) with Candida albicans. The minimal inhibitory concentration (MIC) was determined by the microdilution technique. Additionally, we performed hyphae inhibition and biofilm tests. Finally, experimental candidiasis was evaluated in in vivo models with Wistar female rats. The results showed effective antifungal activity after incorporation into S for all strains tested, with MICs ranging from 31.2 to 62.5 MUg/mL. Microscopic observation of SE revealed an absence of filamentous cells 24 h of exposure to a concentration of 31.2 MUg/mL. E demonstrated no effective action against biofilms, though SE showed inhibition against biofilms of all strains. In the in vivo experiment, SE was effective in the treatment of infection after only two days of treatment and was more effective than E and amphotericin B. The S. nitens is active against Candida albicans (C. albicans) and the antifungal potential is being enhanced after incorporation into liquid crystal precursor systems (LCPS). These findings represent a promising application of SE in the treatment of VVC. PMID- 27556452 TI - The Study of Dynamic Potentials of Highly Excited Vibrational States of DCP: From Case Analysis to Comparative Study with HCP. AB - The dynamic potentials of highly excited vibrational states of deuterated phosphaethyne (DCP) in the D-C and C-P stretching coordinates with anharmonicity and Fermi coupling are studied in this article and the results show that the D-C P bending vibration mode has weak effects on D-C and C-P stretching modes under different Polyad numbers (P number). Furthermore, the dynamic potentials and the corresponding phase space trajectories of DCP are given, as an example, in the case of P = 30. In the end, a comparative study between deuterated phosphaethyne (DCP) and phosphaethyne (HCP) with dynamic potential is done, and it is elucidated that the uncoupled mode makes the original horizontal reversed symmetry breaking between the dynamic potential of HCP ( q 3 ) and DCP ( q 1 ), but has little effect on the vertical reversed symmetry, between the dynamic potential of HCP ( q 2 ) and DCP ( q 3 ). PMID- 27556453 TI - Plasma LncRNA-ATB, a Potential Biomarker for Diagnosis of Patients with Coal Workers' Pneumoconiosis: A Case-Control Study. AB - LncRNA-ATB (lncRNA was activated by transforming growth factor-beta) has been reported to be involved in specific physiological and pathological processes in human diseases, and could serve as biomarkers for cancers. However, the role of lncRNA-ATB in coal workers' pneumoconiosis (CWP) is still unknown. This study aimed to investigate the association between lncRNA-ATB and CWP. Quantitative real-time polymerase chain reaction was performed to detect plasma lncRNA-ATB expression in 137 CWP patients, 72 healthy coal miners and 168 healthy controls. LncRNA-ATB was significantly upregulated in CWP (p < 0.05). Compared with the healthy controls and healthy coal miners, the odds ratios (ORs) (95% confidence interval (CI)) for CWP were 2.57 (1.52-4.33) and 2.17 (1.04-4.53), respectively. LncRNA-ATB was positively associated with transforming growth factor-beta1 (TGF beta1) (r = 0.30, p = 0.003) and negative correlated with vital capacity (VC) (r = -0.18, p = 0.033) and forced vital capacity (FVC) (r = -0.18, p = 0.046) in CWP patients. Compared with healthy controls, the area under the curve (AUC) was 0.84, resulting in a 71.17% sensitivity and 88.14% specificity. When compared with healthy coal miners, the AUC was 0.83, the sensitivity and specificity were 70.07% and 86.36%, respectively. LncRNA-ATB expression is commonly increased in CWP and significantly correlates with the TGF-beta1 in CWP patients. Furthermore, elevated lncRNA-ATB was associated with CWP risk and may serve as a potential biomarker for CWP. PMID- 27556454 TI - The Effects of Female Sexual Hormones on the Expression of Aquaporin 5 in the Late-Pregnant Rat Uterus. AB - Thirteen mammalian aquaporin (AQP) water channels are known, and few of them play a role in the mammalian reproductive system. In our earlier study, the predominance of AQP5 in the late-pregnant rat uterus was proven. Our current aim was to investigate the effect of estrogen- and gestagen-related compounds on the expression of the AQP5 channel in the late-pregnant rat uterus. Furthermore, we examined the effect of hormonally-induced preterm delivery on the expression of AQP5 in the uterus. We treated pregnant Sprague-Dawley rats subcutaneously with 17beta-estradiol, clomiphene citrate, tamoxifen citrate, progesterone, levonorgestrel, and medroxyprogesterone acetate. Preterm delivery was induced by subcutaneous mifepristone and intravaginal prostaglandin E2. Reverse transcriptase PCR and Western blot techniques were used for the detection of the changes in AQP5 mRNA and protein expressions. The amount of AQP5 significantly increased after progesterone and progesterone analogs treatment on 18 and 22 days of pregnancy. The 17beta-estradiol and estrogen receptor agonists did not influence the AQP5 mRNA level; however, estradiol induced a significant increase in the AQP5 protein level on the investigated days of gestation. Tamoxifen increased the AQP5 protein expression on day 18, while clomiphene citrate was ineffective. The hormonally-induced preterm birth significantly decreased the AQP5 level similarly to the day of delivery. We proved that AQP5 expression is influenced by both estrogen and progesterone in the late-pregnant rat uterus. The influence of progesterone on AQP5 expression is more predominant as compared with estrogen. PMID- 27556455 TI - Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson's Disease. AB - Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson's disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA) as umol of pNPA hydrolyzed/min/mg.protein (U/mg protein). hDJ-1 showed maximum reaction velocity esterase activity (Vmax = 235.10 +/- 12.00 U/mg protein), with a sigmoidal fit (S0.5 = 0.55 +/- 0.040 mM) and apparent positive cooperativity (Hill coefficient of 2.05 +/- 0.28). A PD-associated mutant of DJ-1 (M26I) lacked activity. Unlike its protease activity which is inactivated by reactive oxygen species (ROS), esterase activity of hDJ-1 is enhanced upon exposure to low concentrations of hydrogen peroxide (<10 uM) and plateaus at elevated concentrations (>100 uM) suggesting that its activity is resistant to oxidative stress. Esterase activity of DJ-1 requires oxidation of catalytic cysteines, as chemically protecting cysteines blocked its activity whereas an oxido-mimetic mutant of DJ-1 (C106D) exhibited robust esterase activity. Molecular docking studies suggest that C106 and L126 within its catalytic site interact with esterase substrates. Overall, our data show that hDJ-1 contains intrinsic redox sensitive esterase activity that is abolished in a PD-associated mutant form of the hDJ-1 protein. PMID- 27556456 TI - Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model. AB - Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB 231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient's medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model. PMID- 27556457 TI - Synthesis and Evaluation of Novel Oxyalkylated Derivatives of 2',4' Dihydroxychalcone as Anti-Oomycete Agents against Bronopol Resistant Strains of Saprolegnia sp. AB - A series of novel oxyalkylchalcones substituted with alkyl groups were designed and synthesized, and the antioomycete activity of the series was evaluated in vitro against Saprolegnia strains. All tested O-alkylchalcones were synthesized by means of nucleophilic substitution from the natural compound 2',4' dihydroxychalcone (1) and the respective alkyl bromide. The natural chalcone (1) and 10 synthetic oxyalkylchalcones (2-11) were tested against Saprolegnia parasitica and Saprolegnia australis. Among synthetic analogs, 2-hydroxy,4 farnesyloxychalcone (11) showed the most potent activity against Saprolegnia sp., with MIC and MOC values of 125 ug/mL (similar to bronopol at 150 ug/mL) and 175 ug/mL, respectively; however, 2',4'-dihydroxychalcone (1) was the strongest and most active molecule, with MIC and MOC values of 6.25 ug/mL and 12.5 ug/mL. PMID- 27556458 TI - Analysis of Different Ploidy and Parent-Offspring Genomic DNA Methylation in the Loach Misgurnus anguillicaudatus. AB - In this study, we selected natural polyploidy loach (diploid, triploid and tetraploid) and hybrid F1 generation obverse cross (4 * 2) and inverse cross (2 * 4) by diploids and tetraploids as the research model. The MSAP (methylation sensitive amplified polymorphism) reaction system was established by our laboratory to explore methylation levels and pattern diversification features at the whole genome level of the polyploidy loach. The results showed that the total methylation and full methylation rates decreased on increased ploidy individuals; moreover, the hemimethylation rate showed no consistent pattern. Compared with diploid loach, the methylation patterns of tetraploid sites changed 68.17%, and the methylation patterns of triploid sites changed 73.05%. The proportion of hypermethylation genes is significantly higher than the proportion of demethylation genes. The methylation level of reciprocal cross F1 generation is lower than the male diploid and higher than the female tetraploid. The hemimethylation and total methylation rate of the cross hybrid F1 generation is significantly higher than the orthogonal F1 generation (p < 0.01). After readjusting, the methylation pattern of genome DNA of reciprocal hybrids changed 69.59% and 72.83%, respectively. PMID- 27556460 TI - Effect of Pulsed Electric Field on Membrane Lipids and Oxidative Injury of Salmonella typhimurium. AB - Salmonella typhimurium cells were subjected to pulsed electric field (PEF) treatment at 25 kV/cm for 0-4 ms to investigate the effect of PEF on the cytoplasmic membrane lipids and oxidative injury of cells. Results indicated that PEF treatment induced a decrease of membrane fluidity of Salmonella typhimurium (S. typhimuriumi), possibly due to the alterations of fatty acid biosynthesis associated gene expressions (down-regulation of cfa and fabA gene expressions and the up-regulation of fabD gene expression), which, in turn, modified the composition of membrane lipid (decrease in the content ratio of unsaturated fatty acids to saturated fatty acids). In addition, oxidative injury induced by PEF treatment was associated with an increase in the content of malondialdehyde. The up-regulation of cytochrome bo oxidase gene expressions (cyoA, cyoB, and cyoC) indicated that membrane damage was induced by PEF treatment, which was related to the repairing mechanism of alleviating the oxidative injury caused by PEF treatment. Based on these results, we achieved better understanding of microbial injury induced by PEF, suggesting that micro-organisms tend to decrease membrane fluidity in response to PEF treatment and, thus, a greater membrane fluidity might improve the efficiency of PEF treatment to inactivate micro-organisms. PMID- 27556459 TI - Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma. AB - Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2 associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2's potential role as a therapeutic target in HCC. PMID- 27556461 TI - Recognizing the Operating Hand and the Hand-Changing Process for User Interface Adjustment on Smartphones. AB - As the size of smartphone touchscreens has become larger and larger in recent years, operability with a single hand is getting worse, especially for female users. We envision that user experience can be significantly improved if smartphones are able to recognize the current operating hand, detect the hand changing process and then adjust the user interfaces subsequently. In this paper, we proposed, implemented and evaluated two novel systems. The first one leverages the user-generated touchscreen traces to recognize the current operating hand, and the second one utilizes the accelerometer and gyroscope data of all kinds of activities in the user's daily life to detect the hand-changing process. These two systems are based on two supervised classifiers constructed from a series of refined touchscreen trace, accelerometer and gyroscope features. As opposed to existing solutions that all require users to select the current operating hand or confirm the hand-changing process manually, our systems follow much more convenient and practical methods and allow users to change the operating hand frequently without any harm to the user experience. We conduct extensive experiments on Samsung Galaxy S4 smartphones, and the evaluation results demonstrate that our proposed systems can recognize the current operating hand and detect the hand-changing process with 94.1% and 93.9% precision and 94.1% and 93.7% True Positive Rates (TPR) respectively, when deciding with a single touchscreen trace or accelerometer-gyroscope data segment, and the False Positive Rates (FPR) are as low as 2.6% and 0.7% accordingly. These two systems can either work completely independently and achieve pretty high accuracies or work jointly to further improve the recognition accuracy. PMID- 27556462 TI - Channel Measurement and Modeling for 5G Urban Microcellular Scenarios. AB - In order to support the development of channel models for higher frequency bands, multiple urban microcellular measurement campaigns have been carried out in Berlin, Germany, at 60 and 10 GHz. In this paper, the collected data is uniformly analyzed with focus on the path loss (PL) and the delay spread (DS). It reveals that the ground reflection has a dominant impact on the fading behavior. For line of-sight conditions, the PL exponents are close to free space propagation at 60 GHz, but slightly smaller (1.62) for the street canyon at 10 GHz. The DS shows a clear dependence on the scenario (median values between 16 and 38 ns) and a strong distance dependence for the open square and the wide street canyon. The dependence is less distinct for the narrow street canyon with residential buildings. This behavior is consistent with complementary ray tracing simulations, though the simplified model tends to overestimate the DS. PMID- 27556463 TI - Clustering and Beamforming for Efficient Communication in Wireless Sensor Networks. AB - Energy efficiency is a critical issue for wireless sensor networks (WSNs) as sensor nodes have limited power availability. In order to address this issue, this paper tries to maximize the power efficiency in WSNs by means of the evaluation of WSN node networks and their performance when both clustering and antenna beamforming techniques are applied. In this work, four different scenarios are defined, each one considering different numbers of sensors: 50, 20, 10, five, and two nodes per scenario, and each scenario is randomly generated thirty times in order to statistically validate the results. For each experiment, two different target directions for transmission are taken into consideration in the optimization process (phi = 0 degrees and theta = 45 degrees ; phi = 45 degrees , and theta = 45 degrees ). Each scenario is evaluated for two different types of antennas, an ideal isotropic antenna and a conventional dipole one. In this set of experiments two types of WSN are evaluated: in the first one, all of the sensors have the same amount of power for communications purposes; in the second one, each sensor has a different amount of power for its communications purposes. The analyzed cases in this document are focused on 2D surface and 3D space for the node location. To the authors' knowledge, this is the first time that beamforming and clustering are simultaneously applied to increase the network lifetime in WSNs. PMID- 27556464 TI - Mounted Smartphones as Measurement and Control Platforms for Motor-Based Laboratory Test-Beds. AB - Laboratory education in science and engineering often entails the use of test beds equipped with costly peripherals for sensing, acquisition, storage, processing, and control of physical behavior. However, costly peripherals are no longer necessary to obtain precise measurements and achieve stable feedback control of test-beds. With smartphones performing diverse sensing and processing tasks, this study examines the feasibility of mounting smartphones directly to test-beds to exploit their embedded hardware and software in the measurement and control of the test-beds. This approach is a first step towards replacing laboratory-grade peripherals with more compact and affordable smartphone-based platforms, whose interactive user interfaces can engender wider participation and engagement from learners. Demonstrative cases are presented in which the sensing, computation, control, and user interaction with three motor-based test-beds are handled by a mounted smartphone. Results of experiments and simulations are used to validate the feasibility of mounted smartphones as measurement and feedback control platforms for motor-based laboratory test-beds, report the measurement precision and closed-loop performance achieved with such platforms, and address challenges in the development of platforms to maintain system stability. PMID- 27556465 TI - Subsea Cable Tracking by Autonomous Underwater Vehicle with Magnetic Sensing Guidance. AB - The changes of the seabed environment caused by a natural disaster or human activities dramatically affect the life span of the subsea buried cable. It is essential to track the cable route in order to inspect the condition of the buried cable and protect its surviving seabed environment. The magnetic sensor is instrumental in guiding the remotely-operated vehicle (ROV) to track and inspect the buried cable underseas. In this paper, a novel framework integrating the underwater cable localization method with the magnetic guidance and control algorithm is proposed, in order to enable the automatic cable tracking by a three degrees-of-freedom (3-DOF) under-actuated autonomous underwater vehicle (AUV) without human beings in the loop. The work relies on the passive magnetic sensing method to localize the subsea cable by using two tri-axial magnetometers, and a new analytic formulation is presented to compute the heading deviation, horizontal offset and buried depth of the cable. With the magnetic localization, the cable tracking and inspection mission is elaborately constructed as a straight-line path following control problem in the horizontal plane. A dedicated magnetic line-of-sight (LOS) guidance is built based on the relative geometric relationship between the vehicle and the cable, and the feedback linearizing technique is adopted to design a simplified cable tracking controller considering the side-slip effects, such that the under-actuated vehicle is able to move towards the subsea cable and then inspect its buried environment, which further guides the environmental protection of the cable by setting prohibited fishing/anchoring zones and increasing the buried depth. Finally, numerical simulation results show the effectiveness of the proposed magnetic guidance and control algorithm on the envisioned subsea cable tracking and the potential protection of the seabed environment along the cable route. PMID- 27556466 TI - Global Navigation Satellite System Multipath Mitigation Using a Wave-Absorbing Shield. AB - Code multipath is an unmanaged error source in precise global navigation satellite system (GNSS) observation processing that limits GNSS positioning accuracy. A new technique for mitigating multipath by installing a wave-absorbing shield is presented in this paper. The wave-absorbing shield was designed according to a GNSS requirement of received signals and collected measurements to achieve good performance. The wave-absorbing shield was installed at the KUN1 and SHA1 sites of the international GNSS Monitoring and Assessment System (iGMAS). Code and carrier phase measurements of three constellations were collected on the dates of the respective installations plus and minus one week. Experiments were performed in which the multipath of the measurements obtained at different elevations was mitigated to different extents after applying the wave-absorbing shield. The results of an analysis and comparison show that the multipath was mitigated by approximately 17%-36% on all available frequencies of BeiDou Navigation Satellite System (BDS), Global Positioning System (GPS), and Global Navigation Satellite System (GLONASS) satellites. The three-dimensional accuracies of BDS, GPS, and GLONASS single-point positioning (SPP) were, respectively, improved by 1.07, 0.63 and 0.49 m for the KUN1 site, and by 0.72, 0.79 and 0.73 m for the SHA1 site. Results indicate that the multipath of the original observations was mitigated by using the wave-absorbing shield. PMID- 27556467 TI - Factors Influencing Continuous Breath Signal in Intubated and Mechanically Ventilated Intensive Care Unit Patients Measured by an Electronic Nose. AB - INTRODUCTION: Continuous breath analysis by electronic nose (eNose) technology in the intensive care unit (ICU) may be useful in monitoring (patho) physiological changes. However, the application of breath monitoring in a non-controlled clinical setting introduces noise into the data. We hypothesized that the sensor signal is influenced by: (1) humidity in the side-stream; (2) patient-ventilator disconnections and the nebulization of medication; and (3) changes in ventilator settings and the amount of exhaled CO2. We aimed to explore whether the aforementioned factors introduce noise into the signal, and discuss several approaches to reduce this noise. METHODS: Study in mechanically-ventilated ICU patients. Exhaled breath was monitored using a continuous eNose with metal oxide sensors. Linear (mixed) models were used to study hypothesized associations. RESULTS: In total, 1251 h of eNose data were collected. First, the initial 15 min of the signal was discarded. There was a negative association between humidity and Sensor 1 (Fixed-effect beta: -0.05 +/- 0.002) and a positive association with Sensors 2-4 (Fixed-effect beta: 0.12 +/- 0.001); the signal was corrected for this noise. Outliers were most likely due to noise and therefore removed. Sensor values were positively associated with end-tidal CO2, tidal volume and the pressure variables. The signal was corrected for changes in these ventilator variables after which the associations disappeared. CONCLUSION: Variations in humidity, ventilator disconnections, nebulization of medication and changes of ventilator settings indeed influenced exhaled breath signals measured in ventilated patients by continuous eNose analysis. We discussed several approaches to reduce the effects of these noise inducing variables. PMID- 27556468 TI - Virtualized MME Design for IoT Support in 5G Systems. AB - Cellular systems are recently being considered an option to provide support to the Internet of Things (IoT). To enable this support, the 3rd Generation Partnership Project (3GPP) has introduced new procedures specifically targeted for cellular IoT. With one of these procedures, the transmissions of small and infrequent data packets from/to the devices are encapsulated in signaling messages and sent through the control plane. However, these transmissions from/to a massive number of devices may imply a major increase of the processing load on the control plane entities of the network and in particular on the Mobility Management Entity (MME). In this paper, we propose two designs of an MME based on Network Function Virtualization (NFV) that aim at facilitating the IoT support. The first proposed design partially separates the processing resources dedicated to each traffic class. The second design includes traffic shaping to control the traffic of each class. We consider three classes: Mobile Broadband (MBB), low latency Machine to Machine communications (lM2M) and delay-tolerant M2M communications. Our proposals enable reducing the processing resources and, therefore, the cost. Additionally, results show that the proposed designs lessen the impact between classes, so they ease the compliance of the delay requirements of MBB and lM2M communications. PMID- 27556469 TI - A Dielectric-Filled Waveguide Antenna Element for 3D Imaging Radar in High Temperature and Excessive Dust Conditions. AB - Three-dimensional information of the burden surface in high temperature and excessive dust industrial conditions has been previously hard to obtain. This paper presents a novel microstrip-fed dielectric-filled waveguide antenna element which is resistant to dust and high temperatures. A novel microstrip-to dielectric-loaded waveguide transition was developed. A cylinder and cuboid composite structure was employed at the terminal of the antenna element, which improved the return loss performance and reduced the size. The proposed antenna element was easily integrated into a T-shape multiple-input multiple-output (MIMO) imaging radar system and tested in both the laboratory environment and real blast furnace environment. The measurement results show that the proposed antenna element works very well in industrial 3D imaging radar. PMID- 27556470 TI - Monitoring of Grouting Compactness in a Post-Tensioning Tendon Duct Using Piezoceramic Transducers. AB - A post-tensioning tendon duct filled with grout can effectively prevent corrosion of the reinforcement, maintain bonding behavior between the reinforcement and concrete, and enhance the load bearing capacity of concrete structures. In practice, grouting of the post-tensioning tendon ducts always causes quality problems, which may reduce structural integrity and service life, and even cause accidents. However, monitoring of the grouting compactness is still a challenge due to the invisibility of the grout in the duct during the grouting process. This paper presents a stress wave-based active sensing approach using piezoceramic transducers to monitor the grouting compactness in real time. A segment of a commercial tendon duct was used as research object in this study. One lead zirconate titanate (PZT) piezoceramic transducer with marble protection, called a smart aggregate (SA), was bonded on the tendon and installed in the tendon duct. Two PZT patch sensors were mounted on the top outside surface of the duct, and one PZT patch sensor was bonded on the bottom outside surface of the tendon duct. In the active sensing approach, the SA was used as an actuator to generate a stress wave and the PZT sensors were utilized to detect the wave response. Cement or grout in the duct functions as a wave conduit, which can propagate the stress wave. If the cement or grout is not fully filled in the tendon duct, the top PZT sensors cannot receive much stress wave energy. The experimental procedures simulated four stages during the grout pouring process, which includes empty status, half grouting, 90% grouting, and full grouting of the duct. Experimental results show that the bottom PZT sensor can detect the signal when the grout level increases towards 50%, when a conduit between the SA and PZT sensor is formed. The top PZT sensors cannot receive any signal until the grout process is completely finished. The wavelet packet-based energy analysis was adopted in this research to compute the total signal energy received by PZT sensors. Experimental results show that the energy levels of the PZT sensors can reflect the degree of grouting compactness in the duct. The proposed method has the potential to be implemented to monitor the tendon duct grouting compactness of the reinforced concrete structures with post tensioning. PMID- 27556471 TI - Measurement Matrix Optimization and Mismatch Problem Compensation for DLSLA 3-D SAR Cross-Track Reconstruction. AB - With a short linear array configured in the cross-track direction, downward looking sparse linear array three-dimensional synthetic aperture radar (DLSLA 3-D SAR) can obtain the 3-D image of an imaging scene. To improve the cross-track resolution, sparse recovery methods have been investigated in recent years. In the compressive sensing (CS) framework, the reconstruction performance depends on the property of measurement matrix. This paper concerns the technique to optimize the measurement matrix and deal with the mismatch problem of measurement matrix caused by the off-grid scatterers. In the model of cross-track reconstruction, the measurement matrix is mainly affected by the configuration of antenna phase centers (APC), thus, two mutual coherence based criteria are proposed to optimize the configuration of APCs. On the other hand, to compensate the mismatch problem of the measurement matrix, the sparse Bayesian inference based method is introduced into the cross-track reconstruction by jointly estimate the scatterers and the off-grid error. Experiments demonstrate the performance of the proposed APCs' configuration schemes and the proposed cross-track reconstruction method. PMID- 27556472 TI - Fault Diagnosis Strategies for SOFC-Based Power Generation Plants. AB - The success of distributed power generation by plants based on solid oxide fuel cells (SOFCs) is hindered by reliability problems that can be mitigated through an effective fault detection and isolation (FDI) system. However, the numerous operating conditions under which such plants can operate and the random size of the possible faults make identifying damaged plant components starting from the physical variables measured in the plant very difficult. In this context, we assess two classical FDI strategies (model-based with fault signature matrix and data-driven with statistical classification) and the combination of them. For this assessment, a quantitative model of the SOFC-based plant, which is able to simulate regular and faulty conditions, is used. Moreover, a hybrid approach based on the random forest (RF) classification method is introduced to address the discrimination of regular and faulty situations due to its practical advantages. Working with a common dataset, the FDI performances obtained using the aforementioned strategies, with different sets of monitored variables, are observed and compared. We conclude that the hybrid FDI strategy, realized by combining a model-based scheme with a statistical classifier, outperforms the other strategies. In addition, the inclusion of two physical variables that should be measured inside the SOFCs can significantly improve the FDI performance, despite the actual difficulty in performing such measurements. PMID- 27556473 TI - Recognition of Daily Gestures with Wearable Inertial Rings and Bracelets. AB - Recognition of activities of daily living plays an important role in monitoring elderly people and helping caregivers in controlling and detecting changes in daily behaviors. Thanks to the miniaturization and low cost of Microelectromechanical systems (MEMs), in particular of Inertial Measurement Units, in recent years body-worn activity recognition has gained popularity. In this context, the proposed work aims to recognize nine different gestures involved in daily activities using hand and wrist wearable sensors. Additionally, the analysis was carried out also considering different combinations of wearable sensors, in order to find the best combination in terms of unobtrusiveness and recognition accuracy. In order to achieve the proposed goals, an extensive experimentation was performed in a realistic environment. Twenty users were asked to perform the selected gestures and then the data were off-line analyzed to extract significant features. In order to corroborate the analysis, the classification problem was treated using two different and commonly used supervised machine learning techniques, namely Decision Tree and Support Vector Machine, analyzing both personal model and Leave-One-Subject-Out cross validation. The results obtained from this analysis show that the proposed system is able to recognize the proposed gestures with an accuracy of 89.01% in the Leave-One-Subject-Out cross validation and are therefore promising for further investigation in real life scenarios. PMID- 27556474 TI - USLE-Based Assessment of Soil Erosion by Water in the Nyabarongo River Catchment, Rwanda. AB - Soil erosion has become a serious problem in recent decades due to unhalted trends of unsustainable land use practices. Assessment of soil erosion is a prominent tool in planning and conservation of soil and water resource ecosystems. The Universal Soil Loss Equation (USLE) was applied to Nyabarongo River Catchment that drains about 8413.75 km2 (33%) of the total Rwanda coverage and a small part of the Southern Uganda (about 64.50 km2) using Geographic Information Systems (GIS) and Remote Sensing technologies. The estimated total annual actual soil loss was approximately estimated at 409 million tons with a mean erosion rate of 490 t.ha(-1).y(-1) (i.e., 32.67 mm.y(-1)). The cropland that occupied 74.85% of the total catchment presented a mean erosion rate of 618 t.ha( 1).y(-1) (i.e., 41.20 mm.y(-1)) and was responsible for 95.8% of total annual soil loss. Emergency soil erosion control is required with a priority accorded to cropland area of 173,244 ha, which is extremely exposed to actual soil erosion rate of 2222 t.ha(-1).y(-1) (i.e., 148.13 mm.y(-1)) and contributed to 96.2% of the total extreme soil loss in the catchment. According to this study, terracing cultivation method could reduce the current erosion rate in cropland areas by about 78%. Therefore, the present study suggests the catchment management by constructing check dams, terracing, agroforestry and reforestation of highly exposed areas as suitable measures for erosion and water pollution control within the Nyabarongo River Catchment and in other regions facing the same problems. PMID- 27556475 TI - The Accessibility, Usability, and Reliability of Chinese Web-Based Information on HIV/AIDS. AB - OBJECTIVE: The present study was designed to assess the quality of Chinese language Internet-based information on HIV/AIDS. METHODS: We entered the following search terms, in Chinese, into Baidu and Sogou: "HIV/AIDS", "symptoms", and "treatment", and evaluated the first 50 hits of each query using the Minervation validation instrument (LIDA tool) and DISCERN instrument. RESULTS: Of the 900 hits identified, 85 websites were included in this study. The overall score of the LIDA tool was 63.7%; the mean score of accessibility, usability, and reliability was 82.2%, 71.5%, and 27.3%, respectively. Of the top 15 sites according to the LIDA score, the mean DISCERN score was calculated at 43.1 (95% confidence intervals (CI) = 37.7-49.5). Noncommercial websites showed higher DISCERN scores than commercial websites; whereas commercial websites were more likely to be found in the first 20 links obtained from each search engine than the noncommercial websites. CONCLUSIONS: In general, the HIV/AIDS related Chinese language websites have poor reliability, although their accessibility and usability are fair. In addition, the treatment information presented on Chinese language websites is far from sufficient. There is an imperative need for professionals and specialized institutes to improve the comprehensiveness of web based information related to HIV/AIDS. PMID- 27556476 TI - Well-Being and Diabetes Management in Early Pregnant Women with Type 1 Diabetes Mellitus. AB - This paper explores well-being and diabetes management in women with type 1 diabetes mellitus (DM) in early pregnancy and investigates associations among perceived well-being, diabetes management, and maternal characteristics. Questionnaires were answered by 168 Swedish women. Correlation analyses were conducted with Spearman's correlation coefficient (rs). The women reported relatively high scores of self-efficacy in diabetes management (SWE-DES-10: 3.91 (0.51)) and self-perceived health (excellent (6.5%), very good (42.3%), good (38.7%), fair (11.3%) and poor (1.2%)). Moderate scores were reported for general well-being (WBQ-12: 22.6 (5.7)) and sense of coherence (SOC-13: 68.9 (9.7), moderate/low scores for hypoglycemia fear (SWE-HFS 26.6 (11.8)) and low scores of diabetes-distress (SWE-PAID-20 27.1 (15.9)). A higher capability of self-efficacy in diabetes management showed positive correlations with self-perceived health (rs = -0.41, p < 0.0001) and well-being (rs = 0.34, p < 0.0001) as well as negative correlations with diabetes distress (rs = -0.51, p < 0.0001) and hypoglycemia worries (rs = -0.27, p = 0.0009). Women with HbA1c levels of <=48 mmL/mol scored higher in the subscales "goal achievement" in SWE-DES (p = 0.0028) and "comprehensibility" in SOC (p = 0.016). Well-being and diabetes management could be supported by strengthening the women's capability to achieve glycemic goals and their comprehensibility in relation to the treatment. Further studies are needed to test this. PMID- 27556477 TI - Performance Evaluation of the VIDAS((r)) Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection. AB - The objective of this study is primarily to compare the performance of the VIDAS((r)) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost((r)) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA((r)) (Microimmune). The sensitivity and the agreement of the VIDAS((r)) Measles IgG assay compared to the Enzygnost((r)) Anti measles Virus/IgG assay and the Measles IgG CAPTURE EIA((r)) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS((r)) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS((r)) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) < 0.3 and a strong avidity as an AI > 0.6. The VIDAS((r)) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID- 27556478 TI - Assessment of Domestic Pigs, Wild Boars and Feral Hybrid Pigs as Reservoirs of Hepatitis E Virus in Corsica, France. AB - In Corsica, extensive pig breeding systems allow frequent interactions between wild boars and domestic pigs, which are suspected to act as reservoirs of several zoonotic diseases including hepatitis E virus (HEV). In this context, 370 sera and 166 liver samples were collected from phenotypically characterized as pure or hybrid wild boars, between 2009 and 2012. In addition, serum and liver from 208 domestic pigs belonging to 30 farms were collected at the abattoir during the end of 2013. Anti-HEV antibodies were detected in 26% (21%-31.6%) of the pure wild boar, 43.5% (31%-56.7%) of hybrid wild boar and 88% (82.6%-91.9%) of the domestic pig sera. In addition, HEV RNA was detected in five wild boars, three hybrid wild boars and two domestic pig livers tested. Our findings provide evidence that both domestic pig and wild boar (pure and hybrid) act as reservoirs of HEV in Corsica, representing an important zoonotic risk for Corsican hunters and farmers but also for the large population of consumers of raw pig liver specialties produced in Corsica. In addition, hybrid wild boars seem to play an important ecological role in the dissemination of HEV between domestic pig and wild boar populations, unnoticed to date, that deserves further investigation. PMID- 27556479 TI - Influenza NA and PB1 Gene Segments Interact during the Formation of Viral Progeny: Localization of the Binding Region within the PB1 Gene. AB - The influenza A virus genome comprises eight negative-sense viral RNAs (vRNAs) that form individual ribonucleoprotein (RNP) complexes. In order to incorporate a complete set of each of these vRNAs, the virus uses a selective packaging mechanism that facilitates co-packaging of specific gene segments but whose molecular basis is still not fully understood. Recently, we used a competitive transfection model where plasmids encoding the A/Puerto Rico/8/34 (PR8) and A/Udorn/307/72 (Udorn) PB1 gene segments were competed to show that the Udorn PB1 gene segment is preferentially co-packaged into progeny virions with the Udorn NA gene segment. Here we created chimeric PB1 genes combining both Udorn and PR8 PB1 sequences to further define the location within the Udorn PB1 gene that drives co segregation of these genes and show that nucleotides 1776-2070 of the PB1 gene are crucial for preferential selection. In vitro assays examining specific interactions between Udorn NA vRNA and purified vRNAs transcribed from chimeric PB1 genes also supported the importance of this region in the PB1-NA interaction. Hence, this work identifies an association between viral genes that are co selected during packaging. It also reveals a region potentially important in the RNP-RNP interactions within the supramolecular complex that is predicted to form prior to budding to allow one of each segment to be packaged in the viral progeny. Our study lays the foundation to understand the co-selection of specific genes, which may be critical to the emergence of new viruses with pandemic potential. PMID- 27556480 TI - From Cells to Virus Particles: Quantitative Methods to Monitor RNA Packaging. AB - In cells, positive strand RNA viruses, such as Retroviridae, must selectively recognize their full-length RNA genome among abundant cellular RNAs to assemble and release particles. How viruses coordinate the intracellular trafficking of both RNA and protein components to the assembly sites of infectious particles at the cell surface remains a long-standing question. The mechanisms ensuring packaging of genomic RNA are essential for viral infectivity. Since RNA packaging impacts on several essential functions of retroviral replication such as RNA dimerization, translation and recombination events, there are many studies that require the determination of RNA packaging efficiency and/or RNA packaging ability. Studies of RNA encapsidation rely upon techniques for the identification and quantification of RNA species packaged by the virus. This review focuses on the different approaches available to monitor RNA packaging: Northern blot analysis, ribonuclease protection assay and quantitative reverse transcriptase coupled polymerase chain reaction as well as the most recent RNA imaging and sequencing technologies. Advantages, disadvantages and limitations of these approaches will be discussed in order to help the investigator to choose the most appropriate technique. Although the review was written with the prototypic simple murine leukemia virus (MLV) and complex human immunodeficiency virus type 1 (HIV 1) in mind, the techniques were described in order to benefit to a larger community. PMID- 27556481 TI - A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral. AB - Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral. PMID- 27556482 TI - Monitoring of Anti-Hepatitis E Virus Antibody Seroconversion in Asymptomatically Infected Blood Donors: Systematic Comparison of Nine Commercial Anti-HEV IgM and IgG Assays. AB - Diagnosis of hepatitis E virus (HEV) is usually determined serologically by detection of the presence of immunoglobulin (Ig)M antibodies or rising anti-HEV IgG titers. However, serological assays have demonstrated a significant variation in their sensitivities and specificities. In this study, we present the systematic comparison of different immunological anti-HEV assays using complete seroconversion panels of 10 virologically confirmed HEV genotype 3 infected individuals. Assay sensitivities were further evaluated by testing serially diluted World Health Organization (WHO) reference reagent for hepatitis E virus antibody and one patient sample infected with HEV genotype 3. Anti-HEV IgM and IgG antibody presence was determined using the immunological assays Wantai HEV IgM/IgG enzyme-linked immunosorbent assay (ELISA) (Sanbio, Uden, The Netherlands), recomWell HEV IgM/IgG (Mikrogen, Neuried, Germany), HEV IgM ELISA 3.0, HEV ELISA, HEV ELISA 4.0, Assure HEV IgM Rapid Test (all MP Biomedicals Europe, Illkirch Cedex, France) and Anti-HEV ELISA (IgM/IgG, Euroimmun, Lubeck, Germany). The assays showed differences regarding their analytical and diagnostic sensitivities, with anti-HEV IgM assays (n = 5) being more divergent compared to anti-HEV IgG (n = 4) assays in this study. Considerable variations were observed particularly for the detection period of IgM antibodies. This is the first study systematically characterizing serologic assays on the basis of seroconversion panels, providing sample conformity for a conclusive comparison. Future studies should include the assay comparison covering the four different genotypes. PMID- 27556483 TI - Evaluation of the Cross-Protective Efficacy of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus Constructed Based on Two Field Strains. AB - One of the major hurdles to porcine reproductive and respiratory syndrome (PRRS) vaccinology is the limited or no cross-protection conferred by current vaccines. To overcome this challenge, a PRRS chimeric virus (CV) was constructed using an FL12-based cDNA infectious clone in which open reading frames (ORFs) 3-4 and ORFs 5-6 were replaced with the two Korean field isolates K08-1054 and K07 2273,respectively. This virus was evaluated as a vaccine candidate to provide simultaneous protection against two genetically distinct PRRS virus (PRRSV) strains. Thirty PRRS-negative three-week-old pigs were divided into five groups and vaccinated with CV, K08-1054, K07-2273, VR-2332, or a mock inoculum. At 25 days post-vaccination (dpv), the pigs in each group were divided further into two groups and challenged with either K08-1054 or K07-2273. All of the pigs were observed until 42 dpv and were euthanized for pathological evaluation. Overall, the CV-vaccinated group exhibited higher levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-12 (IL-12) expression and of serum virus-neutralizing antibodies compared with the other groups after vaccination and also demonstrated better protection levels against both viruses compared with the challenge control group. Based on these results, it was concluded that CV might be an effective vaccine model that can confer a broader range of cross-protection to various PRRSV strains. PMID- 27556484 TI - Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage. AB - The protective effect of isoflavones on skin damage from ultraviolet (UV) radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05). The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05). Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05). Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05). These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice. PMID- 27556485 TI - Association between Body Mass Index, Waist-to-Height Ratio and Adiposity in Children: A Systematic Review and Meta-Analysis. AB - Obesity is defined as an abnormal or excessive fat accumulation that may impair health. Dual-energy X-ray absorptiometry (DEXA) has been suggested as the gold standard to define obesity, but because its use is complex and expensive, anthropometric measures such as body mass index (BMI) or the waist-to-height ratio (WtHr) have been used as alternatives. The aim of this study was to review the published literature and investigate the correlation of BMI and WtHr with body fat (BF) measured by DEXA in pediatric populations. References were sought in PubMed/Medline and Embase datasets. Five original articles, published between 2013 and 2015, were finally included in this review. Their sample size ranged from 83 to 5355, and the age of participants ranged from 4.9 to 19 years old. The most frequently reported association measurements were the coefficients of determination (R2), followed by correlation coefficients and least-squares regression coefficients. BF measured by DEXA was strongly correlated with both BMI (R2 ranging from 0.32 to 0.91) and WtHr (R2 ranging from 0.49 to 0.73). Thus, either BMI or WtHr may be useful to define obesity when more sophisticated techniques are not available. Our systematic review of the available literature found that neither index demonstrated superiority in assessing obesity in children. PMID- 27556487 TI - Reply to B. Meunier's Letter to the Editor Re: Brewer G. J.; Nutrients 2015, 7, 10053-10064. AB - In a letter to the editor, Meunier [1] apparently attempts to discredit the copper-2 hypothesis for causation of the Alzheimer's disease (AD) epidemic in developed countries proposed by myself in a review in this journal [2].[...]. PMID- 27556488 TI - Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity. AB - Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 +/- 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID- 27556486 TI - Natural Polyphenols for Prevention and Treatment of Cancer. AB - There is much epidemiological evidence that a diet rich in fruits and vegetables could lower the risk of certain cancers. The effect has been attributed, in part, to natural polyphenols. Besides, numerous studies have demonstrated that natural polyphenols could be used for the prevention and treatment of cancer. Potential mechanisms included antioxidant, anti-inflammation as well as the modulation of multiple molecular events involved in carcinogenesis. The current review summarized the anticancer efficacy of major polyphenol classes (flavonoids, phenolic acids, lignans and stilbenes) and discussed the potential mechanisms of action, which were based on epidemiological, in vitro, in vivo and clinical studies within the past five years. PMID- 27556489 TI - Mucosal MicroRNAs Expression Profiles before and after Exclusive Enteral Nutrition Therapy in Adult Patients with Crohn's Disease. AB - MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn's disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C-reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = -0.518, p = 0.008, and r = -0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD. PMID- 27556490 TI - Occurrence of Fusarium langsethiae and T-2 and HT-2 Toxins in Italian Malting Barley. AB - T-2 and HT-2 toxins are two of the most toxic members of type-A trichothecenes, produced by a number of Fusarium species. The occurrence of these mycotoxins was studied in barley samples during a survey carried out in the 2011-2014 growing seasons in climatically different regions in Italy. The percentage of samples found positive ranges from 22% to 53%, with values included between 26 and 787 MUg/kg. The percentage of samples with a T-2 and HT-2 content above the EU indicative levels for barley of 200 MUg/kg ranges from 2% to 19.6% in the 2011 2014 period. The fungal species responsible for the production of these toxins in 100% of positive samples has been identified as Fusarium langsethiae, a well known producer of T-2 and HT-2 toxins. A positive correlation between the amount of F. langsethiae DNA and of the sum of T-2 and HT-2 toxins was found. This is the first report on the occurrence of F. langsethiae-and of its toxic metabolites T-2 and HT-2-in malting barley grown in Italy. PMID- 27556491 TI - Epigenetic Activation of Wnt/beta-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis. AB - Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in liver, is closely associated with central obesity, over-nutrition and other features of metabolic syndrome, which elevate the risk of developing hepatocellular carcinoma (HCC). The Wnt/beta-catenin signaling pathway plays a significant role in the physiology and pathology of liver. Up to half of HCC patients have activation of Wnt/beta-catenin signaling. However, the mutation frequencies of CTNNB1 (encoding beta-catenin protein) or other antagonists targeting Wnt/beta-catenin signaling are low in HCC patients, suggesting that genetic mutations are not the major factor driving abnormal beta-catenin activities in HCC. Emerging evidence has demonstrated that obesity-induced metabolic pathways can deregulate chromatin modifiers such as histone deacetylase 8 to trigger undesired global epigenetic changes, thereby modifying gene expression program which contributes to oncogenic signaling. This review focuses on the aberrant epigenetic activation of Wnt/beta-catenin in the development of NAFLD-associated HCC. A deeper understanding of the molecular mechanisms underlying such deregulation may shed light on the identification of novel druggable epigenetic targets for the prevention and/or treatment of HCC in obese and diabetic patients. PMID- 27556492 TI - Genetic Variants of Retinoic Acid Receptor-Related Orphan Receptor Alpha Determine Susceptibility to Type 2 Diabetes Mellitus in Han Chinese. AB - Retinoic acid receptor-related orphan receptor alpha (RORA) plays a key role in the regulation of lipid and glucose metabolism and insulin expression that are implicated in the development of type 2 diabetes mellitus (T2DM). However, the effects of genetic variants in the RORA gene on the susceptibility to T2DM remain unknown. Nine tagging single-nucleotide polymorphisms (SNPs) were screened by using the SNaPshot method in 427 patients with T2DM and 408 normal controls. Association between genotypes and haplotypes derived from these SNPs with T2DM was analyzed using different genetic models. Allele and genotype frequencies at rs10851685 were significantly different between T2DM patients and control subjects (allele: p = 0.009, Odds ratios (OR) = 1.36 [95% Confidence intervals (CI) = 1.08-1.72]; genotype: p = 0.029). The minor allele T, at rs10851685, was potentially associated with an increased risk of T2DM in the dominant model, displaying OR of 1.38 (95% CI: 1.04-1.82, p = 0.025) in subjects with genotypes TA+TT vs. AA. In haplotype analysis, we observed that haplotypes GGTGTAACT, GGTGTAACC, and GATATAACT were significantly associated with increased risk of T2DM, while haplotypes GATGAAGTT, AGTGAAGTT, and AATGAAATT were protective against T2DM. These data suggest that the genetic variation in RORA might determine a Chinese Han individual's susceptibility to T2DM. PMID- 27556494 TI - The Use of a Fractional Factorial Design to Determine the Factors That Impact 1,3 Propanediol Production from Glycerol by Halanaerobium hydrogeniformans. AB - In recent years, biodiesel, a substitute for fossil fuels, has led to the excessive production of crude glycerol. The resulting crude glycerol can possess a high concentration of salts and an alkaline pH. Moreover, current crude glycerol purification methods are expensive, rendering this former commodity a waste product. However, Halanaerobium hydrogeniformans, a haloalkaliphilic bacterium, possesses the metabolic capability to convert glycerol into 1,3 propanediol, a valuable commodity compound, without the need for salt dilution or adjusting pH when grown on this waste. Experiments were performed with different combinations of 24 medium components to determine their impact on the production of 1,3-propanediol by using a fractional factorial design. Tested medium components were selected based on data from the organism's genome. Analysis of HPLC data revealed enhanced production of 1,3-propanediol with additional glycerol, pH, vitamin B12, ammonium ions, sodium sulfide, cysteine, iron, and cobalt. However, other selected components; nitrate ions, phosphate ions, sulfate ions, sodium:potassium ratio, chloride, calcium, magnesium, silicon, manganese, zinc, borate, nickel, molybdenum, tungstate, copper and aluminum, did not enhance 1,3-propanediol production. The use of a fractional factorial design enabled the quick and efficient assessment of the impact of 24 different medium components on 1,3-propanediol production from glycerol from a haloalkaliphilic bacterium. PMID- 27556493 TI - The Silencing of a 14-3-3E Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability. AB - The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3E isoform from Tenebrio molitor (Tm14-3-3E) in the hemocyte antimicrobial activity. The Tm14-3-3E transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES) sequence, and the peptide binding residues. The Tm14-3-3E transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3E silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3E silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP) into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3E silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3E is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform. PMID- 27556495 TI - Pharmacognostic and Antioxidant Properties of Dracaena sanderiana Leaves. AB - Endogenous and exogenous antioxidants are used to neutralise free radicals and protect the body from free radicals by maintaining the redox balance. The antioxidant properties of Dracaena sanderiana leaves were evaluated using the 2,2 diphenyl-1-picrylhydrazyl (DPPH) assay, and the total phenolic and flavonoid contents were measured. The classes of secondary metabolites were evaluated through pharmacognostic studies, and active compounds were identified by gas chromatography mass-spectrometry (GC-MS). All ethanol-water extracts and D. sanderiana leaf powder were positive for tannins, saponins, terpenoids, cardiac glycosides, and quinones. Flavonoids were present in 100%, 80%, 60%, and 40% ethanol extracts (E100, E80, E60, and E40). E100 showed the highest total flavonoid content, whereas E60 extract showed the highest antioxidant activity and total phenolic content. GC-MS revealed the presence of glycerol, 2,3-dihydro 3,5-dihydroxy-6-methyl-(4H)-pyran-4-one, n-dodecanoic acid, tetradecanoid acid, (n-) hexadecanoid acid, and n-octadecanoic acid in the E60 extract. PMID- 27556496 TI - The rhetoric and reality of nursing in aged care: views from the inside. AB - BACKGROUND: Aged care services and nursing roles are evolving in response to policy reform and increasing consumer expectations, however the nursing workforce is declining in numbers. AIMS: To examine registered nurses' perceptions and experiences of working in aged care. METHODS: Descriptive, exploratory study involving thematic analysis of individual interviews. RESULTS: Key issues related to: professional role strain; workforce challenges; managing expectations, relationships and communication; balancing rights and risk in decision-making; changing models of care and impacts of policy and regulation. CONCLUSION: Expectations and perceptions of aged care nursing are unclear and conflicted. Nurses face significant challenges in meeting consumer, profession, organisational, and policy expectations amidst workforce instability and resource constraints. Structural barriers and aged care policy environments represent significant threats to sustaining nursing in aged care. PMID- 27556497 TI - Calcitonin gene-related peptide down-regulates bleomycin-induced pulmonary fibrosis. AB - We have found that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis, and up-regulation of eIF3a induced by TGF-beta1 is mediated via the ERK1/2 pathway. Whether ERK1/2 - eIF3a signal pathway is involved in calcitonin gene-related peptide (CGRP)-mediated pathogenesis of bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. Sensory CGRP depletion by capsaicin exacerbated bleomycin-induced pulmonary fibrosis in rats, as shown by a significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, accompanied with increased expression of TGF-beta1, eIF3a, phosphorylated ERK1/2, alpha-SMA, collagen I, and collagen III. Exogenous application of CGRP significantly inhibited TGF-beta1 induced proliferation and differentiation of pulmonary fibroblasts concomitantly with decreased expression of eIF3a, phosphorylated ERK1/2, alpha-SMA, collagen I, and collagen III. These effects of CGRP were abolished in the presence of CGRP8 37. These results suggest that endogenous CGRP is related to the development of pulmonary fibrosis induced by bleomycin, and the inhibitory effect of CGRP on proliferation of lung fibroblasts involves the ERK1/2 - eIF3a signaling pathway. PMID- 27556498 TI - Correction: Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1. AB - [This corrects the article DOI: 10.1371/journal.pgen.1006226.]. PMID- 27556499 TI - Inhibition of ARC decreases the survival of HEI-OC-1 cells after neomycin damage in vitro. AB - Hearing loss is a common sensory disorder mainly caused by the loss of hair cells (HCs). Noise, aging, and ototoxic drugs can all induce apoptosis in HCs. Apoptosis repressor with caspase recruitment domain(ARC) is a key factor in apoptosis that inhibits both intrinsic and extrinsic apoptosis pathways; however, there have been no reports on the role of ARC in HC loss in the inner ear. In this study, we used House Ear Institute Organ of Corti 1 (HEI-OC-1) cells, which is a cochlear hair-cell-like cell line, to investigate the role of ARC in aminoglycoside-induced HC loss. ARC was expressed in the cochlear HCs as well as in the HEI-OC-1 cells, but not in the supporting cells, and the expression level of ARC in HCs was decreased after neomycin injury in both cochlear HCs and HEI-OC 1 cells, suggesting that reduced levels of ARC might correlate with neomycin induced HC loss. We inhibited ARC expression using siRNA and found that this significantly increased the sensitivity of HEI-OC-1 cells to neomycin toxicity. Finally, we found that ARC inhibition increased the expression of pro-apoptotic factors, decreased the mitochondrial membrane potential, and increased the level of reactive oxygen species (ROS) after neomycin injury, suggesting that ARC inhibits cell death and apoptosis in HEI-OC-1 cells by controlling mitochondrial function and ROS accumulation. Thus the endogenous anti-apoptotic factor ARC might be a new therapeutic target for the prevention of aminoglycoside-induced HC loss. PMID- 27556500 TI - The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo. AB - Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells. PMID- 27556501 TI - RALB provides critical survival signals downstream of Ras in acute myeloid leukemia. AB - Mutations that activate RAS proto-oncogenes and their effectors are common in acute myeloid leukemia (AML); however, efforts to therapeutically target Ras or its effectors have been unsuccessful, and have been hampered by an incomplete understanding of which effectors are required for AML proliferation and survival. We investigated the role of Ras effector pathways in AML using murine and human AML models. Whereas genetic disruption of NRAS(V12) expression in an NRAS(V12) and Mll-AF9-driven murine AML induced apoptosis of leukemic cells, inhibition of phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) signaling did not reproduce this effect. Conversely, genetic disruption of RALB signaling induced AML cell death and phenocopied the effects of suppressing oncogenic Ras directly - uncovering a novel role for RALB signaling in AML survival. Knockdown of RALB led to decreased phosphorylation of TBK1 and reduced BCL2 expression, providing mechanistic insight into RALB survival signaling in AML. Notably, we found that patient-derived AML blasts have higher levels of RALB TBK1 signaling compared to normal blood leukocytes, supporting a pathophysiologic role for RALB signaling for AML patients. Overall, our work provides new insight into the specific roles of Ras effector pathways in AML and has identified RALB signaling as a key survival pathway. PMID- 27556502 TI - Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma. AB - Aberrant expression of choline kinase alpha (CHKA) has been reported in a variety of human malignancies including colorectal carcinoma (CRC). However, the role of CHKA in the progression and prognosis of CRC remains unknown. In this study, we found that CHKA was frequently upregulated in CRC clinical samples and CRC derived cell lines and was significantly correlated with lymph node metastasis (p = 0.028), TNM stage (p = 0.009), disease recurrence (p = 0.004) and death (p < 0.001). Survival analyses indicated that patients with higher CHKA expression had a significantly shorter disease-free survival (DFS) and disease-specific survival (DSS) than those with lower CHKA expression. Multivariate analyses confirmed that increased CHKA expression was an independent unfavorable prognostic factor for CRC patients. In addition, combination of CHKA with TNM stage was a more powerful predictor of poor prognosis than either parameter alone. Functional study demonstrated that knockdown of CHKA expression profoundly suppressed the growth and metastasis of CRC cells both in vitro and in vivo. Mechanistic investigation revealed that EGFR/PI3K/AKT pathway was essential for mediating CHKA function. In conclusion, our results provide the first evidence that CHKA contributes to tumor progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target in CRC. PMID- 27556503 TI - Immunosuppressive effect of bladder cancer on function of dendritic cells involving of Jak2/STAT3 pathway. AB - Function of dendritic cells (DCs) is impaired by some cancer cells. However, the effect of bladder cancer cell (BCC) on phenotype and function of DCs remains unclear. In this study, healthy human peripheral blood mononuclear cells (PBMCs) derived DCs were co-cultured with BCC pumc-91 and adriamycin-resistant pumc 91/ADM. The expression of DC markers and costimulatory molecules decreased after co-culture. Co-cultured DCs rapidly underwent apoptosis, and had a declined capability to produce IL-8 and RANTES. Furthermore, co-cultured DCs showed impaired allogeneic T cell proliferation and T cell-derived cytokine secretion. Finally, AG490, a Jak2/STAT3 inhibitor, restored the expression of DC markers and costimulatory molecules. Of note, compared with control DCs, DCs co-cultured with pumc-91 produced more IP-10; DCs co-cultured with pumc-91/ADM secreted more MIG. Taken together, these results suggest BCC may inhibit maturation and function of DCs involving of Jak2/STAT3 pathway, and there may be different mechanisms by which adriamycin-resistant BCC restrains DC function in antitumor immune response. PMID- 27556504 TI - FAM65B controls the proliferation of transformed and primary T cells. AB - Cell quiescence is controlled by regulated genome-encoded programs that actively express genes which are often down-regulated or inactivated in transformed cells. Among them is FoxO1, a transcription factor that imposes quiescence in several cell types, including T lymphocytes. In these cells, the FAM65B encoding gene is a major target of FOXO1. Here, we show that forced expression of FAM65B in transformed cells blocks their mitosis because of a defect of the mitotic spindle, leading to G2 cell cycle arrest and apoptosis. Upon cell proliferation arrest, FAM65B is engaged in a complex containing two proteins well known to be involved in cell proliferation i.e. the HDAC6 deacetylase and the 14.3.3 scaffolding protein. In primary T cells, FAM65B is down-regulated upon T cell receptor engagement, and maintaining its expression blocks their proliferation, establishing that the decrease of FAM65B expression is required for proliferation. Conversely, inhibiting FAM65B expression in naive T lymphocytes decreases their activation threshold. These results identify FAM65B as a potential new target for controlling proliferation of both transformed and normal cells. PMID- 27556505 TI - Common housekeeping proteins are upregulated in colorectal adenocarcinoma and hepatocellular carcinoma, making the total protein a better "housekeeper". AB - Housekeeping proteins are essential endogenous controls for normalization as they are expected to be stably expressed. However, the stability of the expression level of housekeeping proteins needs to be assessed considering various experimental conditions. Our study evaluated the degree of variability of 7 commonly used housekeeping proteins with regard to their potential utility as normalizers in 56 pairs of matched colorectal adenocarcinoma (CRC) tissue samples and 6 pairs of hepatocellular carcinoma (HCC) tissue samples using multiple reaction monitoring (MRM) and Western blot analyses. A comprehensive experimental design and strict statistical analysis revealed that the expression levels of these 7 housekeeping proteins were not as stable as expected and they all exhibited upregulations to varying degrees in both the CRC and the HCC tissue samples. Consequently, we verified that using the amount of total protein instead of that of an individual protein can serve as a preferable control for studies of protein expression that require normalization. PMID- 27556506 TI - Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation. AB - Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer. PMID- 27556507 TI - In vitro comparison of conventional hyperthermia and modulated electro hyperthermia. AB - Radiofrequency-induced hyperthermia (HT) treatments for cancer include conventional capacitive coupling hyperthermia (cCHT) and modulated electro hyperthermia (mEHT). In this study, we directly compared these methods with regard to in vitro cytotoxicity and mechanisms of action under isothermal conditions. Hepatoma (HepG2) cells were exposed to HT treatment (42 degrees C for 30 min) using mEHT, cCHT or a water bath. mEHT produced a much higher apoptosis rate (43.1% +/- 5.8%) than cCHT (10.0% +/- 0.6%), the water bath (8.4% +/- 1.7%) or a 37 degrees C control (6.6% +/- 1.1%). The apoptosis-inducing effect of mEHT at 42 degrees C was similar to that achieved with a water bath at 46 degrees C. mEHT also increased expression of caspase-3, 8 and 9. All three hyperthermia methods increased intracellular heat shock protein 70 (Hsp70) levels, but only mEHT greatly increased the release of Hsp70 from cells. Calreticulin and E cadherin levels in the cell membrane also increased after mEHT treatment, but not after cCHT or water bath. These results suggest that mEHT selectively deposits energy on the cell membrane and may be a useful treatment modality that targets cancer cell membranes. PMID- 27556508 TI - Decreased TSPAN1 promotes prostate cancer progression and is a marker for early biochemical recurrence after radical prostatectomy. AB - Patients with prostate cancer (PCa) have a variable prognosis. It is challenging to recognize the progressive disease. In this study, we focused on TSPAN1, a new member of the tetraspanin family. Its expression was decreased in progressive PCa and was an independent prognosis factor of biochemical recurrence after radical prostatectomy. In vitro, knockdown and overexpression of TSPAN1 in PCa cell lines showed that TSPAN1 could inhibit cell proliferation and migration. TSPAN1 was positive related to PTEN in both clinical specimen and mouse models. The combination of these two markers could increase their prognosis value especially in low risk patients. In vitro TSPAN1 knockdown resulted in increased Akt phosphorylation and caused evident cell cycle transition from G1 to S phase. Our data suggests that TSPAN1 is a valuable marker to recognize more progressive PCa. PMID- 27556509 TI - Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/ syndecan-1/TGF-beta autocrine loop. AB - Sphingosine-1-phosphate (S1P) induces epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC). However, its underlying mechanism remains largely unknown. In the present study, we investigated the correlation between S1P and syndecan-1 in HCC, the molecular mechanism involved, as well as their roles in EMT of HCC. Results revealed a high serum S1P level presents in patients with HCC, which positively correlated with the serum syndecan-1 level. A significant inverse correlation existed between S1P1 and syndecan-1 in HCC tissues. S1P elicits activation of the PI3K/AKT signaling pathways via S1P1, which triggers HPSE, leading to increases in expression and activity of MMP-7 and leading to shedding and suppression of syndecan-1. The loss of syndecan-1 causes an increase in TGF-beta1 production. The limited chronic increase in TGF-beta1 can convert HCC cells into a mesenchymal phenotype via establishing an MMP-7/Syndecan-1/TGF beta autocrine loop. Finally, TGF-beta1 and syndecan-1 are essential for S1P induced epithelial to mesenchymal transition. Taken together, our study demonstrates that S1P induces advanced tumor phenotypes of HCC via establishing an MMP-7/syndecan-1/TGF-beta1 autocrine loop, and implicates targetable S1P1 PI3K/AKT-HPSE-MMP-7 signaling axe in HCC metastasis. PMID- 27556510 TI - Correlation between body mass index (BMI) and the Gleason score of prostate biopsies in Chinese population. AB - We assessed the correlation between BMI and Gleason score in prostate biopsies in Chinese Population. In this retrospective study, we collected the Gleason score, PSA, BMI, age, race, and other related clinical data on 290 patients who had undergone prostatic biopsy. We then compared the prostate cancer detection rates and Gleason scores between the high BMI group (BMI >= 25; 143 cases) and low BMI group (< 25; 147 cases). Among the 137 patients in whom prostate cancer detected, 70 had high BMIs and 67 had normal BMIs, making the detection rates 48.95% and 45.58% respectively. Seventeen prostate cancer patients had low Gleason scores (Gleason score < 7), while 120 had high Gleason scores (>= 7). Within the high BMI group, 44.76% had high Gleason scores, which was significantly greater than the 38.10% in the low BMI group (P = 0.027). These results indicate that while there was no effect of BMI on the rate of positive prostate cancer biopsies, the rate of high Gleason scores was greater in the high BMI group than the normal BMI group. PMID- 27556511 TI - Rab27A mediated by NF-kappaB promotes the stemness of colon cancer cells via up regulation of cytokine secretion. AB - Recent evidences have unveiled critical roles of cancer stem cells (CSCs) in tumorigenicity, but how interactions between CSC and tumor environments help maintain CSC initiation remains obscure. The small GTPases Rab27A regulates autocrine and paracrine cytokines by monitoring exocytosis of extracellular vesicles, and is reported to promote certain tumor progression. We observe that overexpression of Rab27A increased sphere formation efficiency (SFE) by increasing the proportion of CD44+ and PKH26high cells in HT29 cell lines, and accelerating the growth of colosphere with higher percentage of cells at S phase. Mechanism study revealed that the supernatant derived from HT29 sphere after Rab27A overexpression was able to expand sphere numbers with elevated secretion of VEGF and TGF-beta. In tumor implanting nude mice model, tumor initiation rates and tumor sizes were enhanced by Rab27A with obvious angiogenesis. As a contrast, knocking down Rab27A impaired the above effects. More importantly, the correlation between higher p65 level and Rab27A in colon sphere was detected, p65 was sufficient to induce up-regulation of Rab27A and a functional NF-kappaB binding site in the Rab27A promoter was demonstrated. Altogether, our findings reveal a unique mechanism that tumor environment related NF-kappaB signaling promotes various colon cancer stem cells (cCSCs) properties via an amplified paracrine mechanism regulated by higher Rab27A level. PMID- 27556512 TI - Coupling of LETM1 up-regulation with oxidative phosphorylation and platelet derived growth factor receptor signaling via YAP1 transactivation. AB - Persistent cellular proliferation and metabolic reprogramming are essential processes in carcinogenesis. Here, we performed Gene Set Enrichment Analysis (GSEA) and found that that LETM1, a mitochondrial calcium transporter, is associated with cellular growth signals such as platelet-derived growth factor (PDGF) receptor signaling and insulin signaling pathways. These results were then verified by qRT-PCR and immnunoblotting. Mechanistically, up-regulation of LETM1 induced YAP1 nuclear accumulation, increasing the expression of PDGFB, PDGFRB and THBS4. Consistent with this, LETM1 silencing caused loss of YAP1 nuclear signal, decreasing the expression of PDGFB, PDGFRB and THBS4. Immunohistochemical staining consistently indicated a positive association between LETM1 up regulation, YAP1 nuclear localization and high PDGFB expression. In clinical data analysis, LETM1 up-regulation in thyroid cancer was found to be related to aggressive tumor features such as lymphovascular invasion (LVI, P < 0.001) and lymph node metastasis (LNM, P = 0.011). Multivariate analysis demonstrated that LETM1 up-regulation increases the risk of LVI and LNM (OR = 3.455, 95% CI = 1.537 7.766 and OR = 3.043, 95% CI = 1.282-7.225, respectively). Collectively, these data suggest that up-regulation of LETM1 induces sustained activation of proliferative signaling pathways, such as PDGF signal pathway by AKT induced YAP1 transactivation, resulting in aggressive thyroid cancer phenotypes. PMID- 27556513 TI - Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447. AB - The PIM family kinases promote growth and survival of tumor cells and are expressed in a wide variety of human cancers. Their potential as therapeutic targets, however, is complicated by overlapping activities with multiple other pathways and remains poorly defined in most clinical scenarios. Here we explore activity of the new pan-PIM inhibitor PIM447 in a variety of lymphoid-derived tumors. We find strong activity in cell lines derived from the activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Sensitive lines show lost activation of the mTORC1 signaling complex and subsequent lost activation of cap dependent protein translation. In addition, we characterize recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases. PMID- 27556514 TI - ROCK inhibitor reduces Myc-induced apoptosis and mediates immortalization of human keratinocytes. AB - The Myc/Max/Mad network plays a critical role in cell proliferation, differentiation and apoptosis and c-Myc is overexpressed in many cancers, including HPV-positive cervical cancer cell lines. Despite the tolerance of cervical cancer keratinocytes to high Myc expression, we found that the solitary transduction of the Myc gene into primary cervical and foreskin keratinocytes induced rapid cell death. These findings suggested that the anti-apoptotic activity of E7 in cervical cancer cells might be responsible for negating the apoptotic activity of over-expressed Myc. Indeed, our earlier in vitro studies demonstrated that Myc and E7 synergize in the immortalization of keratinocytes. Since we previously postulated that E7 and the ROCK inhibitor, Y-27632, were members of the same functional pathway in cell immortalization, we tested whether Y-27632 would inhibit apoptosis induced by the over-expression of Myc. Our findings indicate that Y-27632 rapidly inhibited Myc-induced membrane blebbing and cellular apoptosis and, more generally, functioned as an inhibitor of extrinsic and intrinsic pathways of cell death. Most important, Y-27632 cooperated with Myc to immortalize keratinocytes efficiently, indicating that apoptosis is a major barrier to Myc-induced immortalization of keratinocytes. The anti-apoptotic activity of Y-27632 correlated with a reduction in p53 serine 15 phosphorylation and the consequent reduction in the expression of downstream target genes p21 and DAPK1, two genes involved in the induction of cell death. PMID- 27556515 TI - Antigen specific immune response in Chlamydia muridarum genital infection is dependent on murine microRNAs-155 and -182. AB - Anti-chlamydial immunity involves efficient presentation of antigens (Ag) to effector cells resulting in Ag-specific immune responses. There is limited information on inherent underlying mechanisms regulating these events. Previous studies from our laboratory have established that select microRNAs (miRs) function as molecular regulators of immunity in Chlamydia muridarum (Cm) genital infection. In this report, we investigated immune cell type-specific miRs, i.e. miR-155 and -182, and the role in Ag-specific immunity. We observed significant up-regulation of miR-155 in C57BL/6 bone marrow derived dendritic cells (BMDC), and miR-182 in splenic Ag-specific CD4+ T-cells. Using mimics and inhibitors, we determined that miR-155 contributed to BMDC activation following Cm infection. Co cultures of miR-155 over-expressed in BMDC and miR-182 over-expressed in Ag specific CD4+ T-cells, or miR-155-/- BMDC with miR-182 inhibitor treated Ag specific CD4+ T-cells, resulted in IFN-gamma production comparable to Ag-specific CD4+ T-cells isolated from Cm infected mice. Additionally, miR-182 was significantly up-regulated in intranasally vaccinated mice protected against Cm infection. In vivo depletion of miR-182 resulted in reduction in Ag-specific IFN gamma and genital pathology in Cm infected mice. To the best of our knowledge, this is the first study to report an interaction of miR-155 (in Cm infected DC) and miR-182 (in CD4+ T-cell) resulting in Ag specific immune responses against genital Cm. PMID- 27556516 TI - Expression of non-secreted IL-4 is associated with HDAC inhibitor-induced cell death, histone acetylation and c-Jun regulation in human gamma/delta T-cells. AB - Previously, the expression of a non-secreted IL-4 variant (IL-4delta13) has been described in association with apoptosis and age-dependent Th2 T-cell polarization. Signaling pathways involved in this process have so far not been studied. Here we report the induction of IL-4delta13 expression in human gammadelta T-cells upon treatment with a sublethal dose of histone deacetylase (HDACi) inhibitor valproic acid (VPA). Induction of IL-4delta13 was associated with increased cytoplasmic IL-4Ralpha and decreased IL-4 expression, while mRNA for mature IL-4 was concomitantly down-regulated. Importantly, only the simultaneous combination of apoptosis and necroptosis inhibitors prevented IL 4delta13 expression and completely abrogated VPA-induced global histone H3K9 acetylation mark. Further, our work reveals a novel involvement of transcription factor c-Jun in the signaling network of IL-4, HDAC1, caspase-3 and mixed lineage kinase domain-like protein (MLKL). This study provides novel insights into the effects of epigenetic modulator VPA on human gammadelta T-cell differentiation. PMID- 27556517 TI - Adrenomedullin blockade suppresses sunitinib-resistant renal cell carcinoma growth by targeting the ERK/MAPK pathway. AB - PURPOSE: To evaluate the mechanisms underlying sunitinib resistance in RCC and to identify targets that may be used to overcome this resistance. RESULTS: Reanalysis of transcriptome microarray datasets (GSE64052 and GSE76068) showed that adrenomedullin expression was increased in sunitinib-resistant tumors. And adrenomedullin expression was increased in sunitinib-resistant tumor xenografts, accompanied by upregulation of phospho-ERK levels. However, blocking adrenomedullin inhibited sunitinib-resistant tumor growth. Treatment of RCC cells with sunitinib and ADM22-52 was superior to monotherapy with either agent. Additionally, adrenomedullin upregulated cAMP and activated the ERK/MAPK pathway, promoting cell proliferation, while knockdown of adrenomedullin inhibited RCC cell growth and invasion in vitro. MATERIALS AND METHODS: We searched the Gene Expression Omnibus (GEO) database to find data regarding sunitinib-resistant RCC. These data were subsequently reanalyzed to identify targets that contribute to sunitinib resistance, and adrenomedullin upregulation was found to mediate sunitinib resistance in RCC. Then, we created an RCC mouse xenograft model. Mice were treated with sunitinib, an adrenomedullin receptor antagonist (ADM22-52), a MEK inhibitor (PD98059) and different combinations of these three drugs to investigate their effects on tumor growth. RCC cells (786-0) were cultured in vitro and treated with an ADM22-52 or PD98059 to determine whether adrenomedullin activates the ERK/MAPK pathway. Adrenomedullin was knocked down in 786-0 cells via siRNA, and the effects of this knockdown on cell were subsequently investigated. CONCLUSIONS: Adrenomedullin plays an important role in RCC resistance to sunitinib treatment. The combination of sunitinib and an adrenomedullin receptor antagonist may result in better outcomes in advanced RCC patients. PMID- 27556518 TI - Gender Identification Using High-Frequency Speech Energy: Effects of Increasing the Low-Frequency Limit. AB - OBJECTIVE: The purpose of this study was to investigate the ability of normal hearing listeners to use high-frequency energy for gender identification from naturally produced speech signals. DESIGN: Two experiments were conducted using a repeated-measures design. Experiment 1 investigated the effects of increasing high-pass filter cutoff (i.e., increasing the low-frequency spectral limit) on gender identification from naturally produced vowel segments. Experiment 2 studied the effects of increasing high-pass filter cutoff on gender identification from naturally produced sentences. Confidence ratings for the gender identification task were also obtained for both experiments. RESULTS: Listeners in experiment 1 were capable of extracting talker gender information at levels significantly above chance from vowel segments high-pass filtered up to 8.5 kHz. Listeners in experiment 2 also performed above chance on the gender identification task from sentences high-pass filtered up to 12 kHz. CONCLUSIONS: Cumulatively, the results of both experiments provide evidence that normal hearing listeners can utilize information from the very high-frequency region (above 4 to 5 kHz) of the speech signal for talker gender identification. These findings are at variance with current assumptions regarding the perceptual information regarding talker gender within this frequency region. The current results also corroborate and extend previous studies of the use of high-frequency speech energy for perceptual tasks. These findings have potential implications for the study of information contained within the high-frequency region of the speech spectrum and the role this region may play in navigating the auditory scene, particularly when the low-frequency portion of the spectrum is masked by environmental noise sources or for listeners with substantial hearing loss in the low-frequency region and better hearing sensitivity in the high-frequency region (i.e., reverse slope hearing loss). PMID- 27556519 TI - Prospective Study of Gastroesophageal Reflux, Use of Proton Pump Inhibitors and H2-Receptor Antagonists, and Risk of Hearing Loss. AB - OBJECTIVES: Gastroesophageal reflux disease (GERD) is common and often treated with proton pump inhibitors (PPIs) or H2-receptor antagonists (H2-RAs). GERD has been associated with exposure of the middle ear to gastric contents, which could cause hearing loss. Treatment of GERD with PPIs and H2-RAs may decrease exposure of the middle ear to gastric acid and decrease the risk of hearing loss. We prospectively investigated the relation between GERD, use of PPIs and H2-RAs, and the risk of hearing loss in 54,883 women in Nurses' Health Study II. DESIGN: Eligible participants, aged 41 to 58 years in 2005, provided information on medication use and GERD symptoms in 2005, answered the question on hearing loss in 2009 or in 2013, and did not report hearing loss starting before the date of onset of GERD symptoms or medication use. The primary outcome was self-reported hearing loss. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS: During 361,872 person-years of follow-up, 9842 new cases of hearing loss were reported. Compared with no GERD symptoms, higher frequency of GERD symptoms was associated with higher risk of hearing loss (multivariable adjusted relative risks: <1 time/month 1.04 [0.97, 1.11], several times/week 1.17 [1.09, 1.25], daily 1.33 [1.19, 1.49]; p value for trend <0.001). After accounting for GERD symptoms, neither PPI nor H2-RA use was associated with the risk of hearing loss. CONCLUSIONS: GERD symptoms are associated with higher risk of hearing loss in women, but use of PPIs and H2-RAs are not independently associated with the risk. PMID- 27556520 TI - The Benefits of Increased Sensation Level and Bandwidth for Spatial Release From Masking. AB - OBJECTIVE: Spatial release from masking (SRM) can increase speech intelligibility in complex listening environments. The goal of the present study was to document how speech-in-speech stimuli could be best processed to encourage optimum SRM for listeners who represent a range of ages and amounts of hearing loss. We examined the effects of equating stimulus audibility among listeners, presenting stimuli at uniform sensation levels (SLs), and filtering stimuli at two separate bandwidths. DESIGN: Seventy-one participants completed two speech intelligibility experiments (36 listeners in experiment 1; all 71 in experiment 2) in which a target phrase from the coordinate response measure (CRM) and two masking phrases from the CRM were presented simultaneously via earphones using a virtual spatial array, such that the target sentence was always at 0 degree azimuth angle and the maskers were either colocated or positioned at +/-45 degrees. Experiments 1 and 2 examined the impacts of SL, age, and hearing loss on SRM. Experiment 2 also assessed the effects of stimulus bandwidth on SRM. RESULTS: Overall, listeners' ability to achieve SRM improved with increased SL. Younger listeners with less hearing loss achieved more SRM than older or hearing-impaired listeners. It was hypothesized that SL and bandwidth would result in dissociable effects on SRM. However, acoustical analysis revealed that effective audible bandwidth, defined as the highest frequency at which the stimulus was audible at both ears, was the best predictor of performance. Thus, increasing SL seemed to improve SRM by increasing the effective bandwidth rather than increasing the level of already audible components. CONCLUSIONS: Performance for all listeners, regardless of age or hearing loss, improved with an increase in overall SL and/or bandwidth, but the improvement was small relative to the benefits of spatial separation. PMID- 27556522 TI - Effects of Implantation and Reimplantation of Cochlear Implant Electrodes in an In Vivo Animal Experimental Model (Macaca fascicularis). AB - OBJECTIVES: The objectives of this study were to evaluate the effect of reimplanting a cochlear implant electrode in animal normal-hearing cochlea to propose measures that may prevent cochlear injury and, given its close phylogenetic proximity to humans, to evaluate the macaque as a model for electroacoustic stimulation. DESIGN: Simultaneous, bilateral surgical procedures in a group of 5 normal-hearing specimens (Macaca fascicularis) took place in a total of 10 ears. Periodic bilateral auditory testing (distortion product otoacoustic emissions and auditory brainstem evoked responses [ABR]) took place during a 6-month follow-up period. Subsequently, unilateral explantation and reimplantation was performed. Auditory follow-up continued up to 12 months, after which animals were sacrificed and both temporal bones extracted for histological analysis. RESULTS: Implantation and reimplantation surgeries were performed without complications in 9 of 10 cases. Full insertion depth was achieved at reimplantation in four of five ears. Auditory evaluation: Statistically significant differences between implanted and reimplanted were observed for the frequencies 2000 and 11,000 Hz, the remaining frequencies showed no differences for distortion product otoacoustic emission. Before the procedure, average thresholds with click-stimuli ABR of the five animals were 40 dB SPL (implanted group) and 40 dB SPL (reimplanted group). One week after first implantation, average thresholds were 55 dB SPL and 60 dB, respectively. After 12 months of follow-up, the average thresholds were 72.5 dB SPL (implanted group) and 65 dB SPL (reimplanted group). Hearing loss appeared during the first weeks after the first implantation and no deterioration was observed thereafter. Differences for ABR under click stimulus were not significant between the two ear groups. Similar results were observed with tone-burst ABR. A 15 dB shift was observed for the implanted group preoperatively versus 1-week post surgery and an additional 17.5 dB shift was seen after 12-month follow-up. For the reimplanted group, a 20 dB shift was observed within the first week post reimplantation surgery and an additional 5 dB after 6 months follow-up. Statistical analysis revealed significant differences between the implanted and reimplanted ear groups for frequencies 4000 Hz (p = 0.034), 12000 Hz (p = 0.031), and 16,000 Hz (p = 0.031). The histological analysis revealed that the electrode insertion was minimally traumatic for the cochlea, mainly indicating rupture of the basilar membrane in the transition area between the basal turn and the first cochlear turn only in Mf1 left ear. CONCLUSIONS: With application of minimally traumatic surgical techniques, it is possible to maintain high rates of hearing preservation after implantation and even after reimplantation. Partial impairment of auditory thresholds may occur during the first weeks after surgery, which remains stable. Considering the tonotopic distribution of the cochlea, we found a correlation between the histological lesions sites and the auditory findings, suggesting that a rupture of the basilar membrane may impact hearing levels. The macaque was observed to be a functionally and anatomically an excellent animal model for cochlear implantation. PMID- 27556521 TI - The Acoustics of Word-Initial Fricatives and Their Effect on Word-Level Intelligibility in Children With Bilateral Cochlear Implants. AB - OBJECTIVES: Previous research has found that relative to their peers with normal hearing (NH), children with cochlear implants (CIs) produce the sibilant fricatives /s/ and /?/ less accurately and with less subphonemic acoustic contrast. The present study sought to further investigate these differences across groups in two ways. First, subphonemic acoustic properties were investigated in terms of dynamic acoustic features that indexed more than just the contrast between /s/ and /?/. Second, the authors investigated whether such differences in subphonemic acoustic contrast between sibilant fricatives affected the intelligibility of sibilant-initial single word productions by children with CIs and their peers with NH. DESIGN: In experiment 1, productions of /s/ and /?/ in word-initial prevocalic contexts were elicited from 22 children with bilateral CIs (aged 4 to 7 years) who had at least 2 years of CI experience and from 22 chronological age-matched peers with NH. Acoustic features were measured from 17 points across the fricatives: peak frequency was measured to index the place of articulation contrast; spectral variance and amplitude drop were measured to index the degree of sibilance. These acoustic trajectories were fitted with growth-curve models to analyze time-varying spectral change. In experiment 2, phonemically accurate word productions that were elicited in experiment 1 were embedded within four-talker babble and played to 80 adult listeners with NH. Listeners were asked to repeat the words, and their accuracy rate was used as a measure of the intelligibility of the word productions. Regression analyses were run to test which acoustic properties measured in experiment 1 predicted the intelligibility scores from experiment 2. RESULTS: The peak frequency trajectories indicated that the children with CIs produced less acoustic contrast between /s/ and /?/. Group differences were observed in terms of the dynamic aspects (i.e., the trajectory shapes) of the acoustic properties. In the productions by children with CIs, the peak frequency and the amplitude drop trajectories were shallower, and the spectral variance trajectories were more asymmetric, exhibiting greater increases in variance (i.e., reduced sibilance) near the fricative-vowel boundary. The listeners' responses to the word productions indicated that when produced by children with CIs, /?/-initial words were significantly more intelligible than /s/-initial words. However, when produced by children with NH, /s/-initial words and /?/-initial words were equally intelligible. Intelligibility was partially predicted from the acoustic properties (Cox & Snell pseudo-R > 0.190), and the significant predictors were predominantly dynamic, rather than static, ones. CONCLUSIONS: Productions from children with CIs differed from those produced by age-matched NH controls in terms of their subphonemic acoustic properties. The intelligibility of sibilant initial single-word productions by children with CIs is sensitive to the place of articulation of the initial consonant (/?/-initial words were more intelligible than /s/-initial words), but productions by children with NH were equally intelligible across both places of articulation. Therefore, children with CIs still exhibit differential production abilities for sibilant fricatives at an age when their NH peers do not. PMID- 27556523 TI - Indices of Effortful Listening Can Be Mined from Existing Electroencephalographic Data. AB - OBJECTIVES: Studies suggest that theta (~4 to 7 Hz), alpha (~8 to 12 Hz), and stimulus-evoked dynamics of the electroencephalogram index effortful listening. Numerous auditory event-related potential datasets exist, without thorough examination of these features. The feasibility of mining those datasets for such features is assessed here. DESIGN: In a standard auditory-oddball paradigm, 12 listeners heard deviant high-frequency tones (10%) interspersed among low frequency tones (90%) "near" or "far" separated in frequency. RESULTS: During active listening (deviance detection; experiment 1), sustained frontal midline theta power, and gamma-band inter-trial phase coherence, were greater for the near condition. No significant "near"/"far" differences were observable during passive exposure to the same sounds (experiment 2). CONCLUSIONS: Increased theta power likely reflects increased utilization of cognitive-control processes (e.g., working memory) that rely on frontal cortical networks. Inter-trial phase coherence differences may reflect differences in attention-modulated stimulus encoding. Reanalysis of existing datasets can usefully inform future work on listening effort. PMID- 27556524 TI - Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli II: Versus Adult Auditory Brainstem Responses. AB - OBJECTIVES: The purpose of the study was to examine the differences in auditory brainstem response (ABR) latency and amplitude indices to the CE-Chirp stimuli in neonates versus young adults as a function of stimulus level, rate, polarity, frequency and gender. DESIGN: Participants were 168 healthy neonates and 20 normal-hearing young adults. ABRs were obtained to air- and bone-conducted CE Chirps and air-conducted CE-Chirp octave band stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps. The effect of stimulus level was also examined with bone-conducted CE-Chirps and CE-Chirp octave band stimuli. The effect of gender was examined across all stimulus manipulations. RESULTS: In general, ABR wave V amplitudes were significantly larger (p < 0.0001) and latencies were significantly shorter (p < 0.0001) for adults versus neonates for all air-conducted CE-Chirp stimuli with all stimulus manipulations. For bone-conducted CE-Chirps, infants had significantly shorter wave V latencies than adults at 15 dB nHL and 45 dB nHL (p = 0.02). Adult wave V amplitude was significantly larger for bone-conducted CE-Chirps only at 30 dB nHL (p = 0.02). The effect of gender was not statistically significant across all measures (p > 0.05). CONCLUSIONS: Significant differences in ABR latencies and amplitudes exist between newborns and young adults using CE-Chirp stimuli. These differences are consistent with differences to traditional click and tone burst stimuli and reflect maturational differences as a function of age. These findings continue to emphasize the importance of interpreting ABR results using age-based normative data. PMID- 27556525 TI - Screening, Education, and Rehabilitation Services for Hearing Loss Provided to Clients with Low Vision: Measured and Perceived Value Among Participants of the Vision-Hearing Project. AB - OBJECTIVES: Combined vision and hearing impairment, termed dual sensory impairment (DSI), is associated with poorer health outcomes compared with a single sensory loss alone. Separate systems of care exist for visual and hearing impairment which potentially limit the effectiveness of managing DSI. To address this, a Hearing Screening Education Model (HSEM) was offered to older adults attending a low-vision clinic in Australia within this pilot study. The present study aimed to evaluate the benefits of seeking help on hearing handicap, self perceived health, and use of community services among those identified with unmet hearing needs after participation in the HSEM. DESIGN: Of 210 older adults (>55 years of age) who completed the HSEM and were referred for follow-up, 169 returned for a follow-up interview at least 12 months later. Of these, 68 (40.2%) sought help, and the majority were seen by a hearing healthcare provider (89.7%). Changes in hearing handicap, quality of life, and reliance on community services between the baseline and 12-month follow-up were compared between those who sought help and those who did not. In addition, the perceived value of the HSEM was assessed. RESULTS: Results showed that there was no significant difference in hearing handicap between those who sought help (mean change -1.02 SD = 7.97, p = 0.3) and those who did not (mean change 0.94 SD = 7.68, p = 0.3), p = 0.18. The mental component of the SF-36 worsened significantly between baseline and follow up measures across the whole group (mean change -2.49 SD = 9.98, p = 0.002). This was largely driven by those not seeking help, rather than those seeking help, but was not significantly different between the two groups. Those who sought help showed a significant reduction in the use of community services compared with those who did not. Further, all participants positively viewed the HSEM's underlying principle of greater integration between vision and hearing services. CONCLUSIONS: These findings suggest a need to further develop and evaluate integrated models of healthcare for older adults with DSI. It also highlights the importance of using broader measures of benefit, other than use of hearing aids to evaluate outcomes of hearing healthcare programs. PMID- 27556526 TI - Age-Related Differences in Listening Effort During Degraded Speech Recognition. AB - OBJECTIVES: The purpose of the present study was to quantify age-related differences in executive control as it relates to dual-task performance, which is thought to represent listening effort, during degraded speech recognition. DESIGN: Twenty-five younger adults (YA; 18-24 years) and 21 older adults (OA; 56 82 years) completed a dual-task paradigm that consisted of a primary speech recognition task and a secondary visual monitoring task. Sentence material in the primary task was either unprocessed or spectrally degraded into 8, 6, or 4 spectral channels using noise-band vocoding. Performance on the visual monitoring task was assessed by the accuracy and reaction time of participants' responses. Performance on the primary and secondary task was quantified in isolation (i.e., single task) and during the dual-task paradigm. Participants also completed a standardized psychometric measure of executive control, including attention and inhibition. Statistical analyses were implemented to evaluate changes in listeners' performance on the primary and secondary tasks (1) per condition (unprocessed vs. vocoded conditions); (2) per task (single task vs. dual task); and (3) per group (YA vs. OA). RESULTS: Speech recognition declined with increasing spectral degradation for both YA and OA when they performed the task in isolation or concurrently with the visual monitoring task. OA were slower and less accurate than YA on the visual monitoring task when performed in isolation, which paralleled age-related differences in standardized scores of executive control. When compared with single-task performance, OA experienced greater declines in secondary-task accuracy, but not reaction time, than YA. Furthermore, results revealed that age-related differences in executive control significantly contributed to age-related differences on the visual monitoring task during the dual-task paradigm. CONCLUSIONS: OA experienced significantly greater declines in secondary-task accuracy during degraded speech recognition than YA. These findings are interpreted as suggesting that OA expended greater listening effort than YA, which may be partially attributed to age-related differences in executive control. PMID- 27556527 TI - Overlap and Nonoverlap Between the ICF Core Sets for Hearing Loss and Otology and Audiology Intake Documentation. AB - OBJECTIVES: The International Classification of Functioning Disability and Health (ICF) Core Sets for Hearing Loss (HL) were developed to serve as a standard for the assessment and reporting of the functioning and health of patients with HL. The aim of the present study was to compare the content of the intake documentation currently used in secondary and tertiary hearing care settings in the Netherlands with the content of the ICF Core Sets for HL. Research questions were (1) to what extent are the ICF Core Sets for HL represented in the Dutch Otology and Audiology intake documentation? (2) are there any extra ICF categories expressed in the intake documentation that are currently not part of the ICF Core Sets for HL, or constructs expressed that are not part of the ICF? DESIGN: Multicenter patient record study including 176 adult patients from two secondary, and two tertiary hearing care settings. The intake documentation was selected from anonymized patient records. The content was linked to the appropriate ICF category from the whole ICF classification using established linking rules. The extent to which the ICF Core Sets for HL were represented in the intake documentation was determined by assessing the overlap between the ICF categories in the Core Sets and the list of unique ICF categories extracted from the intake documentation. Any extra constructs that were expressed in the intake documentation but are not part of the Core Sets were described as well, differentiating between ICF categories that are not part of the Core Sets and constructs that are not part of the ICF classification. RESULTS: In total, otology and audiology intake documentation represented 24 of the 27 Brief ICF Core Set categories (i.e., 89%), and 60 of the 117 Comprehensive ICF Core Set categories (i.e., 51%). Various ICF Core Sets categories were not represented, including higher mental functions (Body Functions), civic life aspects (Activities and Participation), and support and attitudes of family (Environmental Factors). One extra ICF category emerged from the intake documentation that is currently not included in the Core Sets: sleep functions. Various Personal Factors emerged from the intake documentation that are currently not defined in the ICF classification. CONCLUSIONS: The results showed substantial overlap between the ICF Core Sets for HL and the intake documentation of otology and audiology, but also revealed areas of nonoverlap. These findings contribute to the evaluation of the content validity of the Core Sets. The overlap can be viewed as supportive of the Core Sets' content validity. The nonoverlap in Core Sets categories indicates that current Dutch intake procedures may not cover all aspects relevant to patients with ear/hearing problems. The identification of extra constructs suggests that the Core Sets may not include all areas of functioning that are relevant to Dutch Otology and Audiology patients. Consideration of incorporating both aspects into future intake practice deserves attention. Operationalization of the ICF Core Sets categories, including the extra constructs identified in this study, into a practical and integral intake instrument seems an important next step. PMID- 27556528 TI - Missing Data in the Field of Otorhinolaryngology and Head & Neck Surgery: Need for Improvement. AB - OBJECTIVE: Clinical studies are often facing missing data. Data can be missing for various reasons, for example, patients moved, certain measurements are only administered in high-risk groups, and patients are unable to attend clinic because of their health status. There are various ways to handle these missing data (e.g., complete cases analyses, mean substitution). Each of these techniques potentially influences both the analyses and the results of a study. The first aim of this structured review was to analyze how often researchers in the field of otorhinolaryngology/head & neck surgery report missing data. The second aim was to systematically describe how researchers handle missing data in their analyses. The third aim was to provide a solution on how to deal with missing data by means of the multiple imputation technique. With this review, we aim to contribute to a higher quality of reporting in otorhinolaryngology research. DESIGN: Clinical studies among the 398 most recently published research articles in three major journals in the field of otorhinolaryngology/head & neck surgery were analyzed based on how researchers reported and handled missing data. RESULTS: Of the 316 clinical studies, 85 studies reported some form of missing data. Of those 85, only a small number (12 studies, 3.8%) actively handled the missingness in their data. The majority of researchers exclude incomplete cases, which results in biased outcomes and a drop in statistical power. CONCLUSIONS: Within otorhinolaryngology research, missing data are largely ignored and underreported, and consequently, handled inadequately. This has major impact on the results and conclusions drawn from this research. Based on the outcomes of this review, we provide solutions on how to deal with missing data. To illustrate, we clarify the use of multiple imputation techniques, which recently became widely available in standard statistical programs. PMID- 27556529 TI - Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli I: Versus Click and Tone Burst Stimuli. AB - OBJECTIVES: The purpose of the study was to generate normative auditory brainstem response (ABR) wave component peak latency and amplitude values for neonates with air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli (i.e., 500, 1000, 2000, and 4000 Hz). A second objective was to compare neonate ABRs to CE-Chirp stimuli with ABR responses to traditional click and tone burst stimuli with the same stimulus parameters. DESIGN: Participants were 168 healthy neonates. ABRs were obtained to air- and bone-conducted CE-Chirp and click stimuli and air-conducted CE-Chirp octave band and tone burst stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE Chirps and clicks. The effect of stimulus level was also examined with bone conducted CE-Chirps and clicks and air-conducted CE-Chirp octave band stimuli. RESULTS: In general, ABR wave V amplitudes to air- and bone-conducted CE-Chirp stimuli were significantly larger (p < 0.05) than those evoked to traditional click and tone burst stimuli. Systematic statistically significant (p < 0.05) wave V latency differences existed between the air- and bone-conducted CE-Chirp and CE-Chirp octave band stimuli relative to traditional click and tone burst stimuli. CONCLUSIONS: ABRs to air- and bone-conducted CE-Chirps and CE-Chirp octave band stimuli may be valuable in the assessment of newborn infants. However, the prognostic value of such stimuli needs to be validated. PMID- 27556531 TI - Neural Correlates of Selective Attention With Hearing Aid Use Followed by ReadMyQuips Auditory Training Program. AB - OBJECTIVES: The objectives of this study were to investigate the effects of hearing aid use and the effectiveness of ReadMyQuips (RMQ), an auditory training program, on speech perception performance and auditory selective attention using electrophysiological measures. RMQ is an audiovisual training program designed to improve speech perception in everyday noisy listening environments. DESIGN: Participants were adults with mild to moderate hearing loss who were first-time hearing aid users. After 4 weeks of hearing aid use, the experimental group completed RMQ training in 4 weeks, and the control group received listening practice on audiobooks during the same period. Cortical late event-related potentials (ERPs) and the Hearing in Noise Test (HINT) were administered at prefitting, pretraining, and post-training to assess effects of hearing aid use and RMQ training. An oddball paradigm allowed tracking of changes in P3a and P3b ERPs to distractors and targets, respectively. Behavioral measures were also obtained while ERPs were recorded from participants. RESULTS: After 4 weeks of hearing aid use but before auditory training, HINT results did not show a statistically significant change, but there was a significant P3a reduction. This reduction in P3a was correlated with improvement in d prime (d') in the selective attention task. Increased P3b amplitudes were also correlated with improvement in d' in the selective attention task. After training, this correlation between P3b and d' remained in the experimental group, but not in the control group. Similarly, HINT testing showed improved speech perception post training only in the experimental group. The criterion calculated in the auditory selective attention task showed a reduction only in the experimental group after training. ERP measures in the auditory selective attention task did not show any changes related to training. CONCLUSIONS: Hearing aid use was associated with a decrement in involuntary attention switch to distractors in the auditory selective attention task. RMQ training led to gains in speech perception in noise and improved listener confidence in the auditory selective attention task. PMID- 27556530 TI - Prevalence of Hearing Loss Among a Representative Sample of Canadian Children and Adolescents, 3 to 19 Years of Age. AB - OBJECTIVES: There are no nationally representative hearing loss (HL) prevalence data available for Canadian youth using direct measurements. The present study objectives were to estimate national prevalence of HL using audiometric pure-tone thresholds (0.5 to 8 kHz) and or distortion product otoacoustic emissions (DPOAEs) for children and adolescents, aged 3 to 19 years. DESIGN: This cross sectional population-based study presents findings from the 2012/2013 Canadian Health Measures Survey, entailing an in-person household interview and hearing measurements conducted in a mobile examination clinic. The initial study sample included 2591 participants, aged 3 to 19 years, representing 6.5 million Canadians (3.3 million males). After exclusions, subsamples consisted of 2434 participants, aged 3 to 19 years and 1879 participants, aged 6 to 19 years, with valid audiometric results. Eligible participants underwent otoscopic examination, tympanometry, DPOAE, and audiometry. HL was defined as a pure-tone average >20 dB for 6- to 18-year olds and >=26 dB for 19-year olds, for one or more of the following: four-frequency (0.5, 1, 2, and 4 kHz) pure-tone average, high frequency (3, 4, 6, and 8 kHz) pure-tone average, and low-frequency (0.5, 1, and 2 kHz) pure-tone average. Mild HL was defined as >20 to 40 dB (6- to 18-year olds) and >=26 to 40 dB (19-year olds). Moderate or worse HL was defined as >40 dB (6- to 19-year olds). HL in 3- to 5-year olds (n = 555) was defined as absent DPOAEs as audiometry was not conducted. Self-reported HL was evaluated using the Health Utilities Index Mark 3 hearing questions. RESULTS: The primary study outcome indicates that 7.7% of Canadian youth, aged 6 to 19, had any HL, for one or more pure-tone average. Four-frequency pure-tone average and high-frequency pure-tone average HL prevalence was 4.7 and 6.0%, respectively, whereas 5.8% had a low-frequency pure-tone average HL. Significantly more children/adolescents had unilateral HL. Mild HL was significantly more common than moderate or worse HL for each pure-tone average. Among Canadians, aged 6 to 19, less than 2.2% had sensorineural HL. Among Canadians, aged 3 to 19, less than 3.5% had conductive HL. Absent DPOAEs were found in 7.1% of 3- to 5-year olds, and in 3.4% of 6- to 19-year olds. Among participants eligible for the hearing evaluation and excluding missing data cases (n = 2575), 17.0% had excessive or impacted pus/wax in one or both ears. Self-reported HL in Canadians, aged 6 to 19, was 0.6 E% and 65.3% (aged 3 to 19) reported never having had their hearing tested. E indicates that a high sampling variability is associated with the estimate (coefficient of variation between 16.6% and 33.3%) and should be interpreted with caution. CONCLUSIONS: This study provides the first estimates of audiometrically measured HL prevalence among Canadian children and adolescents. A larger proportion of youth have measured HL than was previously reported using self-report surveys, indicating that screening using self-report or proxy may not be effective in identifying individuals with mild HL. Results may underestimate the true prevalence of HL due to the large number excluded and the presentation of impacted or excessive earwax or pus, precluding an accurate or complete hearing evaluation. The majority of 3- to 5-year olds with absent DPOAEs likely had conductive HL. Nonetheless, this type of HL which can be asymptomatic, may become permanent if left untreated. Future research will benefit from analyses, which includes the slight HL category, for which there is growing support, and from studies that identify factors contributing to HL in this population. PMID- 27556532 TI - Prevalence, Awareness, Treatment and Control of Hypertension in Indonesian Adults Aged >=40 Years: Findings from the Indonesia Family Life Survey (IFLS). AB - OBJECTIVE: Hypertension is the major driver of the cardiovascular epidemic facing Indonesia in the 21st century. Understanding the socioeconomic inequalities associated with hypertension is essential for designing effective intervention strategies. The aim of the current study was to use sub-nationally representative survey data to examine socio-demographic inequalities in the prevalence, diagnosis and management of hypertension in Indonesian adults. METHODS: We investigated factors associated with hypertension prevalence, diagnosis, treatment and control using data on self-reported diagnosis and treatment, and blood pressure measurements, collected from 9755 respondents aged 40 years and up in the 2007 Indonesian Family Life Survey (IFLS 4). RESULTS: Age-standardized prevalence of hypertension among the study participants was 47.8% (95% CI: 46.8, 48.9), of which almost 70% were undiagnosed. Hypertension was significantly higher in women than men (52.3% versus 43.1%, p-value<0.001). Prevalence of hypertension increased significantly with ageing (Pfor trend <0.001). Over 91% (men: 92.1%, women: 90.0%) of hypertension cases were uncontrolled. Gender, education and socioeconomic status had differential impact on the diagnosis of hypertension and in receiving treatment. CONCLUSIONS: Overall, less than a third were aware of their hypertension and a quarter of those on medication had their blood pressure effectively controlled. Men and those of younger age were more vulnerable to have undiagnosed and untreated hypertension. Substantial effort should be given to improve awareness about the condition and making provision for early diagnosis and treatment. PMID- 27556533 TI - Sequence Capture and Phylogenetic Utility of Genomic Ultraconserved Elements Obtained from Pinned Insect Specimens. AB - Obtaining sequence data from historical museum specimens has been a growing research interest, invigorated by next-generation sequencing methods that allow inputs of highly degraded DNA. We applied a target enrichment and next-generation sequencing protocol to generate ultraconserved elements (UCEs) from 51 large carpenter bee specimens (genus Xylocopa), representing 25 species with specimen ages ranging from 2-121 years. We measured the correlation between specimen age and DNA yield (pre- and post-library preparation DNA concentration) and several UCE sequence capture statistics (raw read count, UCE reads on target, UCE mean contig length and UCE locus count) with linear regression models. We performed piecewise regression to test for specific breakpoints in the relationship of specimen age and DNA yield and sequence capture variables. Additionally, we compared UCE data from newer and older specimens of the same species and reconstructed their phylogeny in order to confirm the validity of our data. We recovered 6-972 UCE loci from samples with pre-library DNA concentrations ranging from 0.06-9.8 ng/MUL. All investigated DNA yield and sequence capture variables were significantly but only moderately negatively correlated with specimen age. Specimens of age 20 years or less had significantly higher pre- and post-library concentrations, UCE contig lengths, and locus counts compared to specimens older than 20 years. We found breakpoints in our data indicating a decrease of the initial detrimental effect of specimen age on pre- and post-library DNA concentration and UCE contig length starting around 21-39 years after preservation. Our phylogenetic results confirmed the integrity of our data, giving preliminary insights into relationships within Xylocopa. We consider the effect of additional factors not measured in this study on our age-related sequence capture results, such as DNA fragmentation and preservation method, and discuss the promise of the UCE approach for large-scale projects in insect phylogenomics using museum specimens. PMID- 27556534 TI - Hydrogen Generation using non-polar coaxial InGaN/GaN Multiple Quantum Well Structure Formed on Hollow n-GaN Nanowires. AB - This article demonstrates for the first time to the best of our knowledge, the merits of InGaN/GaN multiple quantum wells (MQWs) grown on hollow n-GaN nanowires (NWs) as a plausible alternative for stable photoelectrochemical water splitting and efficient hydrogen generation. These hollow nanowires are achieved by a growth method rather not by conventional etching process. Therefore this approach becomes simplistic yet most effective. We believe relatively low Ga flux during the selective area growth (SAG) aids the hollow nanowire to grow. To compare the optoelectronic properties, simultaneously solid nanowires are also studied. In this present communication, we exhibit that lower thermal conductivity of hollow n-GaN NWs affects the material quality of InGaN/GaN MQWs by limiting In diffusion. As a result of this improvement in material quality and structural properties, photocurrent and photosensitivity are enhanced compared to the structures grown on solid n-GaN NWs. An incident photon-to-current efficiency (IPCE) of around ~33.3% is recorded at 365 nm wavelength for hollow NWs. We believe that multiple reflections of incident light inside the hollow n-GaN NWs assists in producing a larger amount of electron hole pairs in the active region. As a result the rate of hydrogen generation is also increased. PMID- 27556535 TI - Oncologic surgery: a great challenge. PMID- 27556536 TI - Cultural adaptation and the Clavien-Dindo surgical complications classification translated to Brazilian Portuguese. AB - OBJECTIVE: to generate a translated and validated version of the Clavien-Dindo Classification of Surgical Complications (CDC) to Brazilian Portuguese (CDC-BR). METHODS: the process of translation and adaptation followed the guideline of Beaton et al., 2000. We divided 76 participating surgeons, in different levels of experience, from the Department Surgery of the Hospital de Clinicas de Porto Alegre, into two groups: Group I applied the original version (CDC, n=36);r Group II used the modified version (CDC-BR, n=40). Each group classified 15 clinical cases of surgical complications. We compared performance between the groups (Mann Whitney test) relating to the level of experience of the surgeon (Kruskal-Wallis test), considering p value <0.05 as significant. RESULTS: the performance of the Group II (CDC-BR) was higher, with 85% accuracy, compared with 79% of Group I (CDC), p-value =0.012. The performance of the groups as for surgeons experience displayed p=0.171 for Group I, p=0.528 for Group II, and p=0.135 for overall performance. CONCLUSION: we produced a translated and validated version of the CDC for Brazilian Portuguese. The instrument will be a useful tool in the production of evidence on surgical outcomes. OBJETIVO: gerar uma versao traduzida e validada da Classificacao de Complicacoes Cirurgicas de Clavien-Dindo (CCD) para o Portugues-Brasileiro (CCD-BR). METODOS: o processo de traducao e adaptacao seguiu a diretriz de Beaton et al., de 2000. Formaram-se dois grupos, Grupo I, que utilizou a versao original (CCD, n=36) testado em relacao ao Grupo II, com a versao modificada (CCD-BR, n=40), com um total de 76 cirurgioes participantes em niveis de experiencia distintos do Departamento de Cirurgia do Hospital de Clinicas de Porto Alegre. Quinze casos clinicos de complicacoes cirurgicas foram classificados em cada grupo. Comparou-se o desempenho entre grupos (teste de Mann Whitney) relacionando ao nivel de experiencia dos cirurgioes (teste de Kruskal Wallis). Valor de p<0,05 como significativo. RESULTADOS: o desempenho do Grupo II (CCD-BR) foi superior, com 85% de acertos, contra 79% do Grupo I (CCD), p valor=0,012 do teste de Mann-Whitney. O desempenho dos grupos em relacao a experiencia dos cirurgioes foi p-valor=0,171 para o Grupo I, p-valor=0,528 para o Grupo II, e p-valor=0,135 para o desempenho geral, teste de Kruskal-Wallis. CONCLUSAO: foi produzida uma versao traduzida e validada da CCD para o Portugues Brasileiro. O instrumento produzido sera ferramenta util na producao de evidencias sobre os resultados cirurgicos. PMID- 27556537 TI - Type 2 Diabetes Mellitus remission eighteen months after Roux-en-Y gastric bypass. AB - OBJECTIVE: to evaluate the effectiveness of Roux-en-Y gastric bypass in improving the glycemic profile of obese patients with type 2 Diabetes Mellitus (DM2) after 18 months of follow-up. METHODS: four hundred sixty-eight pacients with DM2 and BMI >=35 were submitted to Roux-en-Y gastric bypass, from 1998 to 2010. All patients were submitted to glycemic control analysis in the 3rd, 6th, 9th, 12th and 18th postoperative months. We considered: type 2 diabetic patients, the ones with fasting glucose >=126mg/dl and HbA1C >=6.5 in two dosages; high risk patients for diabetes, those who presented fasting glucose >= 100 to 125 mg/dl and HbA1C between 5.7%-6.4%; and normal patients, those presenting glucose <100mg/dl and HbA1C <5.7%. Such diagnostic criteria were based on the official position of Sociedade Brasileira de Diabetes, published in July, 2011. RESULTS: The remission of DM2 was seen in 410 (87.6%) out of 468 patients 18 months after the surgery, that being a meaningful difference, with p<0.001. Fourty-eight (10.3%) patients sustained criteria for the disease and ten (2.1%) continued at high risk for DM2. CONCLUSIONS: Roux-en-Y gastric bypass was effective in the promotion and maintaince of long-term glycemic control. There are evidences showing that the remission of DM2 is not only related to weight loss and that other enteroinsular axis mechanisms must be involved. OBJETIVO: avaliar a eficacia da gastroplastia com derivacao em Y-de-Roux, em pacientes obesos e portadores de Diabetes Mellitus tipo 2 (DM2), na melhoria do perfil glicemico apos 18 meses de seguimento. METODOS: foram submetidos a derivacao gastrica em Y de-Roux 468 pacientes com IMC >=35 e portadores de DM2, no periodo de 1998 a 2010. Todos os pacientes tiveram a analise do controle glicemico realizadas no terceiro, sexto, nono, 12o e 18o meses de pos-operatorio. Os criterios diagnosticos de diabetes foram baseados no Posicionamento Oficial da Sociedade Brasileira de Diabetes, publicado em julho de 2011. RESULTADOS: observou-se a remissao do DM2 em 410 pacientes (87,6%) apos 18 meses da cirurgia, sendo essa diferenca significativa com p-valor <0,001. A doenca se manteve inalterada em 48 pacientes (10,3%), e dez pacientes (2,1%) permaneceram com o risco aumentado para DM2. CONCLUSAO: a gastroplastia com derivacao em Y-de-Roux foi efetiva na promocao e manutencao do controle glicemico em longo prazo. PMID- 27556538 TI - Alterations of blood flow pattern after triple stent endovascular treatment of saccular abdominal aortic aneurysm: a porcine model. AB - OBJECTIVE: to determine the blood flow pattern changes after endovascular treatment of saccular abdominal aortic aneurysm with triple stent. METHODS: we conducted a hemodynamic study of seven Landrace and Large White pigs with saccular aneurysms of the infrarenal abdominal aorta artificially produced according to the technique described. The animals were subjected to triple stenting for endovascular aneurysm. We evaluated the pattern of blood flow by duplex scan before and after stent implantation. We used the non-paired Mann Whitney test for statistical analysis. RESULTS: there was a significant decrease in the average systolic velocity, from 127.4cm/s in the pre-stent period to 69.81cm/s in the post-stent phase. There was also change in the flow pattern from turbulent in the aneurysmal sac to laminate intra-stent. CONCLUSION: there were changes in the blood flow pattern of saccular abdominal aortic aneurysm after endovascular treatment with triple stent. OBJETIVO: determinar as alteracoes do padrao do fluxo sanguineo apos tratamento endovascular do aneurisma sacular de aorta abdominal com triplo stent. METODOS: estudo hemodinamico de sete suinos das racas Landrace e Large White portadores de aneurismas saculares de aorta abdominal infrarrenal artificialmente produzidos segundo tecnica descrita. Os animais foram submetidos a implante de triplo stent para correcao endovascular do aneurisma e reavaliados por duplex scan quanto ao padrao do fluxo sanguineo antes e apos o implante dos stents. A analise estatistica foi realizada com o teste Mann-Whitney nao pareado. RESULTADOS: verificou-se uma queda significativa da velocidade sistolica media de 127,4cm/s na fase pre-stent para 69,81cm/s na fase pos-stent. Houve ainda mudanca no padrao do fluxo de turbilhonar no saco aneurismatico para laminar intrastent. CONCLUSAO: o estudo demonstrou alteracoes do padrao do fluxo sanguineo do aneurisma sacular de aorta abdominal apos tratamento endovascular com triplo stent. PMID- 27556539 TI - Augmentation mastopexy after bariatric surgery: evaluation of patient satisfaction and surgical results. AB - OBJECTIVE: to evaluate patient satisfaction and surgical results obtained after mastopexy with breast implant inclusion. METHODS: we conducted a prospective study of 20 consecutive female patients with a mean age of 39.9 years, submitted to augmentation mastopexy. We applied semi-directed psychological interviews pre and postoperatively. The answers to the evaluations were tabulated, categorized, and allowed patient satisfaction analysis. We evaluated surgical results through photographic analysis of three independent plastic surgeons, in the pre and postoperative periods, when scores were attributed to the following items: breasts shape, breasts volume, breasts symmetry, nipple-areolar complex position, and scar quality and extent. RESULTS: nineteen patients (95%) referred satisfaction with the surgical results attained (p<0,001). The mean sum of the scores attributed by the three surgeons to each patient varied between 4.7 and 10, with an overall mean of 7.28. The results were considered good or great for 65% of the sample and poor for 8.4%. CONCLUSION: there was a 95% satisfaction rate among patients with the results obtained through augmentation mastopexy. The photographic analysis of the results obtained a mean score of 7.28, considered as a good result, albeit the weak correlation among evaluators. OBJETIVO: avaliar a satisfacao das pacientes e os resultados cirurgicos obtidos apos a mastopexia com inclusao de implantes mamarios. METODOS: estudo prospectivo com 20 pacientes consecutivas do sexo feminino, com media etaria de 39,9 anos, que foram submetidas a mastopexia de aumento. Foram aplicadas entrevistas psicologicas semidirigidas nos periodos pre e pos-operatorios e cujas respostas foram tabuladas, divididas em categorias, e possibilitaram a avaliacao da satisfacao das pacientes. Foi realizada avaliacao dos resultados cirurgicos atraves da analise fotografica por tres cirurgioes plasticos independentes, nos periodos pre e pos-operatorios, que atribuiram notas aos seguintes itens: forma da mama, volume da mama, simetria entre as mamas, posicionamento do complexo areolo papilar e qualidade e extensao das cicatrizes. RESULTADOS: dezenove pacientes (95%) referiram satisfacao com o resultado cirurgico obtido (p<0,001). A media das somatorias das notas atribuidas pelos tres cirurgioes, referentes a cada paciente, variou entre 4,7 e 10, sendo a media geral de 7,28. Os resultados foram considerados bons ou otimos para 65% da amostra e pobres para 8,4%. CONCLUSAO: houve satisfacao de 95% das pacientes com os resultados obtidos pela mastopexia de aumento. A analise fotografica dos resultados obteve nota media de 7,28, caracterizado como bom resultado, apesar da fraca concordancia entre os avaliadores. PMID- 27556540 TI - Comparative evaluation of ventilatory function through pre and postoperative peak expiratory flow in patients submitted to elective upper abdominal surgery. AB - OBJECTIVE: to evaluate the ventilatory function by Peak Expiratory Flow (PEF) in the immediate pre and postoperative periods of patients undergoing elective surgical procedures in the upper abdomen. METHODS: we conducted a prospective cohort study including 47 patients admitted to the Hospital Regional de Mato Grosso do Sul from July to December 2014, who underwent elective surgeries of the upper abdomen, and submiited to spirometric evaluation and measurement of PEF immediately before and after surgery. RESULTS: of the 47 patients, 22 (46.8%) were male and 25 (53.20%) female. The mean preoperative PEF was 412.1+/-91.7, and postoperative, 331.0+/-87.8, indicating significant differences between the two variables. Men had higher PEF values than women, both in the pre and postoperative periods. There was a reasonable inverse correlation between age and decreased PEF. Both situations showed statistical significance (p<0.001). The group of smokers had lower PEF values both before and after surgery. The group of patients with comorbidities (hypertension and/or diabetes) showed lower PEF values both pre and postoperatively (p=0.005). In both groups, surgery resulted in a significant decrease in PEF (p<0.001). The type of surgery performed and the type of anesthesia did not show significant differences. CONCLUSION: the variables most involved in decreased lung function were: advanced age, smoking and presence of comorbidities. However, there is no consistent evidence to suggest conducting routine spirometry in such patients. OBJETIVO: avaliacao comparativa da funcao ventilatoria atraves do Pico de Fluxo Expiratorio (PFE) no pre e pos-operatorio imediatos de pacientes submetidos a procedimentos cirurgicos eletivos do andar superior do abdome. METODOS: estudo prospectivo de coorte incluindo 47 pacientes internados no Hospital Regional de Mato Grosso do Sul de Julho a Dezembro de 2014, e que realizaram cirurgias eletivas do andar superior do abdome, e submetidos a avaliacao espirometrica e afericao do PFE no pre e pos operatorio imediatos. RESULTADOS: dos 47 pacientes, 22 (46,8%) eram do sexo masculino, e 25 (53,20%) do sexo feminino. A media do PFE pre-operatorio foi 412,1+/-91,7, e do pos-operatorio de 331,0+/-87,8, indicando diferencas significantes entre as duas variaveis. O sexo masculino apresentou maiores valores de PFE do que o feminino, tanto no pre-cirurgico quanto no pos-cirurgico. Observou-se razoavel correlacao inversamente proporcional entre as variaveis idade e diminuicao do PFE. Ambas as situacoes mostraram significancia estatistica (p<0,001). O grupo composto por fumantes apresentou menores valores de PFE tanto no pre como no pos-operatorio. O grupo composto por portadores de co-morbidades (HAS e/ou DM) apresentou menores valores de PFE tanto no pre como no pos operatorio (p=0,005). Em ambos os grupos, o pos-operatorio determinou uma diminuicao significativa do PFE (p<0,001). O tipo de cirurgia realizada e o tipo de anestesia nao mostraram diferencas significantes em relacao ao PFE. CONCLUSAO: as variaveis mais implicadas na diminuicao da funcao ventilatoria, avaliadas atraves da PFE, foram: idade avancada, tabagismo e presenca de comorbidades. PMID- 27556541 TI - Multiprofissional electronic protocol in ophtalmology with enfasis in strabismus. AB - OBJECTIVE: to create and validate an electronic database in ophthalmology focused on strabismus, to computerize this database in the form of a systematic data collection software named Electronic Protocol, and to incorporate this protocol into the Integrated System of Electronic Protocols (SINPE(c)). METHODS: this is a descriptive study, with the methodology divided into three phases: (1) development of a theoretical ophthalmologic database with emphasis on strabismus; (2) computerization of this theoretical ophthalmologic database using SINPE(c) and (3) interpretation of the information with demonstration of results to validate the protocol. We inputed data from the charts of fifty patients with known strabismus through the Electronic Protocol for testing and validation. RESULTS: the new electronic protocol was able to store information regarding patient history, physical examination, laboratory exams, imaging results, diagnosis and treatment of patients with ophthalmologic diseases, with emphasis on strabismus. We included 2,141 items in this master protocol and created 20 new specific electronic protocols for strabismus, each with its own specifics. Validation was achieved through correlation and corroboration of the symptoms and confirmed diagnoses of the fifty included patients with the diagnostic criteria for the twenty new strabismus protocols. CONCLUSION: a new, validated electronic database focusing on ophthalmology, with emphasis on strabismus, was successfully created through the standardized collection of information, and computerization of the database using proprietary software. This protocol is ready for deployment to facilitate data collection, sorting and application for practitioners and researchers in numerous specialties. OBJETIVO: criar uma base eletronica de dados em oftalmologia com enfase em estrabismo atraves da coleta padronizada de informacoes. Informatizar esta base sob a forma de software para a coleta sistematica de dados chamado "Protocolo Eletronico" e incorporar este "Protocolo Eletronico" da Oftalmologia ao Sistema Integrado de Protocolos Eletronicos (SINPE(c)). METODOS: este e um estudo descritivo e a metodologia aplicada em seu desenvolvimento esta didaticamente dividida em tres fases: 1) criacao da base teorica de dados clinicos de oftalmologia com enfase em estrabismo; 2) informatizacao da base teorica dos dados utilizando o SINPE(c); e 3) interpretacao das informacoes com demonstracao dos resultados. A informatizacao da base de dados foi realizada pela utilizacao da concessao de uso do SINPE(c). Foram incluidos neste protocolo 50 pacientes com estrabismo para validacao do protocolo. RESULTADOS: o protocolo eletronico desenvolvido permitiu armazenar informacoes relacionadas a anamnese, exame fisico, exames complementares, diagnostico e tratamento de pacientes com doencas oftalmologicas, com enfase em estrabismo. Foram incluidos neste trabalho 2141 itens no protocolo mestre e foram criados 20 protocolos especificos de estrabismo, cada um com suas particularidades. Os 50 pacientes que foram incluidos nos protocolos especificos demonstraram a eficacia do metodo empregado. CONCLUSAO: foi criada uma base eletronica de dados em oftalmologia com enfase em estrabismo atraves da coleta padronizada de informacoes. Esta base de dados foi informatizada sob a forma de software onde os futuros usuarios poderao utilizar o protocolo eletronico multiprofissional de doencas oftalmologicas com enfase em estrabismo para a coleta de seus dados. PMID- 27556542 TI - Comparative analysis of endoscopic and histopathological features of superficial elevated lesions resected by endoscopic mucosal resection in the distal and proximal colon. AB - OBJECTIVE: to compare endoscopic and histopathologic features of superficial, elevated lesions with one or more centimeters in diameter, diagnosed by videocolonoscopy on the distal and proximal colon, and subjected to mucosal resection. METHODS: we conducted a retrospective, cross-sectional, observational study involving 8,075 videocolonoscopies. From this total, we evaluated 166 mucosectomies in 145 patients with superficial, elevated lesions with a diameter equal to or greater than 1cm. RESULTS: the lesion prevalence was lower in G1 than in G2 (34.9% vs. 65%). The mean age, gender distribution and size (1.9cm in G1 versus 2.0cm in G2, p=0.921) were similar. There was no difference of mucosal surfaces in relation to the location (p=0.575). Considering Intraepithelial neoplasias, both the low grade, high grade (including carcinomas) and hyperplasic ones showedd no difference (p=0.527), nor did the neoplastic lesions when divided into serrated and non-serrated (p=0.124). Excluding 13 hyperplastic lesions and two carcinomas, 124 (82.1%) were non-serrated and 27 (17.9%), serrated. CONCLUSION: were found no significant differences between endoscopic and histopathological aspects of superficial, elevated lesions of 1cm or more in diameter in distal colon compared with the proximal, when resected by mucosectomy. Although not significant, there was a tendency of association between the location of the lesion and the presence of serrated features. OBJETIVO: comparar aspectos endoscopicos e histopatologicos de lesoes superficialmente elevadas, com um ou mais centimetros de diametro, diagnosticadas por videocolonoscopias e ressecadas por mucosectomias do colon distal com as do colon proximal. METODOS: estudo foi retrospectivo, transversal, observacional, envolvendo 8075 videocolonoscopias. Avaliou-se 166 mucosectomias em 145 pacientes com lesoes superficialmente elevadas com diametro igual ou maior do que 1cm. RESULTADOS: a prevalencia de lesoes foi menor no G1 do que no G2 (34,9% x 65%). A media de idade, a distribuicao por sexo e o tamanho (1,9cm no G1 e 2cm no G2, p=0,921) foram semelhantes. Nao houve diferencas das superficies em relacao a localizacao (p=0,575). Considerando neoplasia intraepitelial de baixo grau, neoplasia intraepitelial de alto grau (incluindo carcinomas) e hiperplasicas, nao houve diferenca (p=0,527), assim como quando foram divididas as lesoes neoplasicas em serrilhadas e nao serrilhadas (p=0,124). Excluindo-se 13 lesoes hiperplasicas e duas com carcinomas, 124 (82,1%) foram nao serrilhadas e 27 (17,9%) serrilhadas. CONCLUSAO: nao foram observadas diferencas significativas entre os aspectos endoscopicos e os histopatologicos das lesoes superficialmente elevadas, com 1cm ou mais de diametro, ressecadas por mucosectomia do colon distal em relacao ao proximal. Embora nao significante, ha tendencia a associacao entre a localizacao da lesao e a presenca de caracteristicas serrilhadas. PMID- 27556543 TI - Minimally invasive treatment of vesicourethral leak after laparoscopic radical prostatectomy. AB - OBJECTIVE: to describe our experience with a minimally invasive approach for persistent vesicourethral anastomotic leak (PVAL) after Laparoscopic Radical Prostatectomy (LRP). METHODS: from 2004 to 2011, two surgeons performed LRP in 620 patients. Ten patients had PVAL, with initially indicated conservative treatment, to no avail. These patients underwent a minimally invasive operation, consisting of an endoscopically insertion of two ureteral catheters to direct urine flow, fixed to a new urethral catheter. We maintained the ureteral catheters for seven days on average to complete resolution of urine leakage. The urethral catheter was removed after three weeks of surgery. RESULTS: the correction of urine leakage occurred within a range of one to three days, in all ten patients, without complications. There were no stenosis of the bladder neck and urinary incontinence on long-term follow-up. CONCLUSION: the study showed that PVAL after laparoscopic radical prostatectomy can be treated endoscopically with safety and excellent results. OBJETIVO: descrever nossa experiencia com uma abordagem minimamente invasiva para fistula de anastomose vesicouretral persistente (FAVP) apos prostatectomia radical laparoscopica (PRL). METODOS: de 2004 a 2011, 620 pacientes foram submetidos a prostatectomia radical laparoscopica realizada por dois cirurgioes. Dez pacientes apresentaram FAVP e o tratamento conservador foi inicialmente indicado sem sucesso. Esses pacientes foram submetidos a uma reoperacao minimamente invasiva, por via endoscopica, com insercao de dois cateteres ureterais para direcionar o fluxo urinario, fixados a um novo cateter uretral. Os cateteres ureterais foram mantidos por sete dias, em media, ate a completa resolucao do vazamento de urina. O cateter uretral foi removido apos tres semanas da cirurgia. RESULTADOS: a correcao do vazamento de urina ocorreu dentro de um intervalo de um a tres dias em todos os dez pacientes, sem complicacoes. Nao foram observadas estenose de colo vesical ou incontinencia urinaria apos acompanhamento em longo prazo. CONCLUSAO: o estudo mostrou que a FAVP apos a prostatectomia radical laparoscopica pode ser tratada por via endoscopica com seguranca e excelentes resultados. PMID- 27556544 TI - Reliability of nutritional assessment in patients with gastrointestinal tumors. AB - Patients with gastrointestinal cancer and malnutrition are less likely to tolerate major surgical procedures, radiotherapy or chemotherapy. In general, they display a higher incidence of complications such as infection, dehiscence and sepsis, which increases the length of stay and risk of death, and reduces quality of life. The aim of this review is to discuss the pros and cons of different points of view to assess nutritional risk in patients with gastrointestinal tract (GIT) tumors and their viability, considering the current understanding and screening approaches in the field. A better combination of anthropometric, laboratory and subjective evaluations is needed in patients with GIT cancer, since malnutrition in these patients is usually much more severe than in those patients with tumors at sites other than the GIT. RESUMO Pacientes com neoplasia gastrointestinal e desnutridos sao menos propensos a tolerar procedimentos cirurgicos de grande porte, radioterapia ou quimioterapia. Em geral, apresentam maior incidencia de complicacoes, como infeccao, deiscencia e sepse, o que aumenta o tempo de internacao e o risco de morte, e reduz a qualidade de vida. O objetivo desta revisao e abordar os pros e contras de diferentes pontos de vista que avaliam risco nutricional em pacientes com tumores do Trato Gastrointestinal (TGI) e sua viabilidade, considerando o atual entendimento e abordagens de triagem neste campo. Melhor combinacao de avaliacoes antropometricas, laboratoriais e subjetivas se faz necessaria em pacientes com cancer do TGI, uma vez que a desnutricao nestes pacientes costuma ser muito mais grave do que naqueles individuos com tumores em outros sitios que nao o TGI. PMID- 27556545 TI - Minilaparoscopy-assisted transumbilical laparoscopic cholecystectomy. AB - The role of laparoscopy in the modern surgery era is well established. With the prospect of being able to improve the already privileged current situation, new alternatives have been proposed, such as natural orifice endoscopic surgery (NOTES), the method for single transumbilical access (LESS - Laparo-endoscopic single-site surgery) and minilaparoscopy (MINI). The technique proposed by the authors uses a laparoscope with an operative channel like the flexible endoscope used in NOTES. All operative times are carried out through the umbilical trocar as in LESS, and assisted by a minilaparoscopy grasper. This new technic combines, and results from, the rationalization of technical particularities and synergy of these three approaches, seeking to join their advantages and minimize their disadvantages. RESUMO O papel da videolaparoscopia na era moderna da cirurgia encontra-se bem estabelecido. Com a perspectiva de ser possivel melhorar a ja privilegiada situacao atual, novas alternativas tem sido propostas, como a cirurgia por orificios naturais (NOTES), o metodo por acesso unico transumbilical (LESS - Laparo-endoscopic single-site surgery) e a minilaparoscopia (MINI). A tecnica proposta pelos autores utiliza-se de optica com canal de trabalho como o endoscopio flexivel do NOTES, executa-se todos os tempos operatorios pelo trocarte umbilical, como no LESS, e e assistido por pinca de minilaparoscopia. Esta nova tecnica combina e resulta da racionalizacao de particularidades tecnicas e do sinergismo destas tres abordagens, buscando agregar suas vantagens e minimizar as suas desvantagens. PMID- 27556546 TI - The history of the parathyroid surgery. AB - The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment. RESUMO Os autores fizeram uma revisao dos principais aspectos historicos da progressao do conhecimento sobre o tratamento cirurgico do hiperparatireoidismo. Por meio de revisao bibliografica, foram analisados artigos selecionados sobre a historia da evolucao do conhecimento anatomico, fisiologico, patologico e cirurgico das glandulas paratireoides. Devido as suas caracteristicas anatomicas peculiares, as paratireoides foram as ultimas das glandulas endocrinas a serem descobertas, o que dificultou sobremaneira seu tratamento adequado ate as primeiras decadas do Seculo XX. A evolucao tecnologica ocorrida nos ultimos 30 anos facilitou sobremaneira a localizacao das glandulas e a cirurgia do hiperparatireoidismo. Contudo, um cirurgiao experiente e dedicado ao tratamento dessa enfermidade ainda e fundamental para a excelencia do tratamento. PMID- 27556548 TI - Attentive processes, blood lactate and CrossFit(r). AB - OBJECTIVES: To analyze the influences of blood lactate produced during a specific session of CrossFit(r) on intensity and selectivity of attention. The first was evaluated by measuring the reaction time and the second by analyzing divided attention with a dual task. METHODS: Fifteen male professionals of CrossFit(r) volunteered in the study. The training session was the Workout Of the Day (WOD) called 15.5, marked as: 27-21-15-9 repetitions (without recovery) in term of calories measured by using a rowing ergometer (e.g. 27 rowed calories) and in term of barbell full squats (raising a weight of 43 kg for men and of 29.5 kg for women). Blood lactate, blood glucose, reaction time, execution time of a dual task, number of errors and number of omissions were measured at rest, at the conclusion of the session and 15 minutes after its end. RESULTS: The levels of the blood lactate before the start of the session were considerably higher than those which normally occur at rest (<2 mmol /L), with a mean value of 4.5 mmol /l (+/- 1.99 SD). At the end of the workout session the blood lactate exhibited a significant increase, reaching a mean value of 13.8 mmol /l (+/- 1.18 SD) and then returning to values similar to the initial ones after 15 minutes. Blood glucose did not exhibit any statistically significant differences during the session. Reaction time, execution time, number of errors and number of omissions exhibited a significant worsening concomitantly with the increase in blood lactate. CONCLUSION: Athletes practicing CrossFit(r), with high levels of blood lactate even at rest, should consequently have attentional performances somewhat limited. PMID- 27556547 TI - Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1. AB - During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells. PMID- 27556549 TI - Individual differences in emotional processing and autobiographical memory: interoceptive awareness and alexithymia in the fading affect bias. AB - The capacity to perceive internal bodily states is linked to emotional awareness and effective emotional regulation. We explore individual differences in emotional awareness in relation to the fading affect bias (FAB), which refers to the greater dwindling of unpleasant compared to pleasant emotions in autobiographical memory. We consider interoceptive awareness and alexithymia in relation to the FAB, and private event rehearsal as a mediating process. With increasing interoceptive awareness, there was an enhanced FAB, but with increasing alexithymia, there was a decreased FAB. Further, the effects of interoceptive awareness were partially mediated by private rehearsal of pleasant events. We provide novel evidence that capacity for emotional awareness and thus effective processing is an important factor predictive of the FAB. Moreover, our results imply an important role for maintaining positive affect in the FAB. Our findings offer new insights into the effects of interoception and alexithymia on autobiographical memory, and support concepts of the FAB emerging as a result of adaptive emotional regulation processes. PMID- 27556550 TI - Dental pain, use of dental services and oral health-related quality of life in southern Brazil. AB - This study aimed at assessing the relationship between dental pain and the reason for using dental services and oral health quality of life in people aged 50 to 74 years in southern Brazil. A cross-sectional population-based study was conducted with 720 individuals aged 50 to 74 years, living in three health districts in the city of Porto Alegre. Dental impacts on daily life and sociodemographic data were assessed using structured interviews. The Oral Impacts on Daily Performance - OIDP instrument was used to measure oral impacts. The information was analyzed by Poisson regression with robust variance adjustment, taking into account cluster sampling. Dental pain was present in 32.5% of those reporting an oral impact on their daily activities. Dental pain most frequently affected talking (37.6%), cleaning teeth and gums (37.0%) and enjoying the companionship of people (36.5%). After adjustments to the multivariate analysis, the reason for dental visits due to dental pain was found to have a high impact on daily activities [RP 1.68 (1.11 - 2.54]. PMID- 27556551 TI - Evaluation of children's dental anxiety levels at a kindergarten and at a dental clinic. AB - This study evaluated the dental anxiety levels of preschool children at a kindergarten and at a dental clinic. The anxiety levels of ninety 4-6-year-old (4.99 +/- 0.81) preschool children were evaluated according to pulse rates, the facial image scale (FIS), the Venham picture test (VPT), and the Frankl behavior rating scale. The children's mothers were asked to complete the state-trait anxiety inventory (STAI) forms 1 and 2 (STAI 2 and STAI 2). The sample t-test, Mann-Whitney U test, and Pearson's correlation test were used. A statistically significant difference was observed between the children's pulse rates when measured at the dental clinic and those when measured at the kindergarten (p < 0.001). Although the results were not statistically significant, more negative facial expressions were observed in the children at the dental clinic than in those at the kindergarten when assessed using FIS and VPT (p = 0.090 and p = 0.108, respectively). There was a statistically significant correlation between the transient anxiety levels (STAI 1) of mothers and the VPT scores of their children evaluated at the dental clinic (r = 0.506, p < 0.001). The continuous anxiety level of the mothers of males was found to be significantly higher (p = 0.033) than that of the mothers of females (STAI 2). Although the children had been informed about dentistry and were introduced to a dentist at the kindergarten, their anxiety levels seemingly increased as they arrived at the dental clinic. The significant increase observed in the children's pulse rates was a physical indicator that their anxiety levels had increased. It can be concluded that the children felt more anxious at the dental clinic that at the kindergarten. PMID- 27556552 TI - Tissue characterization following revascularization of immature dog teeth using different disinfection pastes. AB - Revascularization of immature teeth with necrotic pulps traditionally involves the use of triple antibiotic paste, which may sometimes lead to undesirable complications. The objective of this study was to assess tissue repair in immature dog teeth with apical periodontitis subjected to revascularization, comparing two different pastes used for root canal disinfection. Apical periodontitis was induced in 30 dog premolars. Teeth were randomly divided into three experimental groups: root canals filled with triple antibiotic paste (n = 10); root canals filled with 1% propolis paste (n = 10); and no medication (n = 10). An additional group (n = 10, no intervention) was used as control. After 7 months, the jaws were histologically evaluated for the following variables: newly formed mineralized tissue (present/absent); vital tissue in the canal space (absent/periodontal ligament-like/pulp-like); apical extension of root (present/absent); and severity of inflammatory process (absent/mild/moderate/severe). There were no statistically significant differences among the experimental groups in new mineralized tissue formation and apical root development. The formation of vital tissue in the canal space, in turn, was statistically different between the triple paste and propolis groups: vital tissues were present in all revascularized teeth disinfected with propolis paste (100%), compared to 71% of those disinfected with the triple paste. Severity of inflammatory process was different between the triple paste and no medication groups. The new tissues formed onto canal walls and in the root canal space showed characteristics of cementum and periodontal ligament, respectively. Propolis may have some advantages over the triple paste for the revascularization of immature teeth. PMID- 27556553 TI - Relined fiberglass post: an ex vivo study of the resin cement thickness and dentin-resin interface. AB - The aim of this study was to evaluate the thickness of resin cements in the root thirds when using conventional fiberglass posts (CP) and relined fiberglass posts (RP) in weakened roots and to evaluate the morphological characteristics of the dentin-resin interface. Forty human maxillary anterior teeth had the crown sectioned below the cemento-enamel junction. The canals were endodontically treated and weakened with diamond burs. Teeth were divided into four groups (n = 10): Group 1 - CP + RelyX ARC; Group 2 - CP + RelyX U200; Group 3 - RP + RelyX ARC; and Group 4 - RP + RelyX U200. Prior to luting, 0.1% Fluorescein and 0.1% Rhodamine B dyes were added to an adhesive and resin cement, respectively. Slices were obtained from the apical, middle, and cervical thirds of the root. Confocal laser scanning microscopy images were recorded in four areas (buccal, lingual, mesial, distal) of each third. In each area, four equidistant measures of the resin cement were made and the mean value was calculated. The interface morphology was observed. The data were submitted to three-way ANOVA and Tukey's test (alpha = 0.05). The interaction between fiberglass posts, resin cement, and root thirds was significant (p < 0.0001). The resin cement thicknesses were significantly lower for RP in comparison with CP, except in the apical third. There was no significant difference between the resin cements for RP. There was formation of resin cement tags and adhesive tags along the root for RP. RP favored the formation of thin and uniform resin cement films and resin tags in weakened roots. PMID- 27556554 TI - Effects of modeling liquid/resin and polishing on the color change of resin composite. AB - Modeling liquids/resins have been used to build up resin composite (RC) restorations, although there is a lack of information regarding their effects on the color stability of the latter. Therefore, the purpose of the present study was to evaluate the effects of the presence of modeling liquid between layers of RC and the finishing/polishing state of the material on color change in specimens exposed to red wine staining over time. Specimens were prepared by placing four increments (+/-0.5 mm thick) of RC (FiltekTM Z350 XT, 3M ESPE) into molds; half of which were prepared by applying modeling liquid (ScotchbondTM Multi-PurposeTM Adhesive, SBMP, 3M ESPE) between the layers of RC, whereas the other half were prepared without SBMP (control). Light-activation was performed after application of the final RC layer using a light-emitting diode (Radii, SDI) curing unit with an irradiance of 900 mW/cm2 for 20 s. Each group was divided according to the surface finishing protocol (n = 7): nothing (non-polished) or polishing with Sof LexTM/diamond paste (polished). Initial colors of the specimens were evaluated with a digital spectrophotometer and the CIEL*a*b* color system. The specimens were stored in wine (37 degrees C) for 12 months, and the color measurements were reassessed after 4, 6, and 12 months of storage. Scanning electron microscopy (SEM) analysis was performed at the end. Data were analyzed using ANOVA and Tukey's test (alpha = 5%). The presence of SBMP resulted in lower overall color change of the RC as compared with the control. The non-polished specimens exhibited a significantly higher color change than the polished specimens. SEM images corroborated the previous findings. In summary, the use of modeling liquid between layers of RC shows potential for application to reduce or delay the staining process of RC over time. Moreover, polishing is essential to provide increased color stability of the RC restoration. PMID- 27556555 TI - Clinical and radiographic sequelae to primary teeth affected by dental trauma: a 9-year retrospective study. AB - This retrospective study aimed at determining the predicted risks of clinical and radiographic complications in primary teeth following traumatic dental injuries, according to injury type, severity and child's age. Data were collected from records of children treated at a Dental Trauma Center in Brazil for nine years. Records of 576 children were included; clinical sequelae were assessed in 774 teeth, and radiographic sequelae, in 566 teeth. A total of 408 teeth (52.7%) had clinical sequelae and 185 teeth (32.7%), radiographic sequelae. The type of injury with the highest number of clinical sequelae was the crown-root fracture (86.4%). Clinical sequelae increased with injury severity (p < 0.001), whereas radiographic sequelae did not (0.236). The predicted risk of color change was 29.0% (95%CI 19-41) for teeth with enamel fracture, and 26.0% (95%CI 14-40) for teeth with enamel dentin fracture as well as enamel dentin pulp fracture. Risk of periapical radiolucency was higher for teeth with enameldentinpulp fracture (61.1% 95%CI 35-82) and those with subluxation (15.8% 95%CI 10-22). Risk of premature loss was 27.3% (95%CI 13-45) for teeth with extrusive luxation, and 10.2% (95%CI 5-17) for those with intrusive luxation. The assessment of predicted risks of sequelae showed that teeth with hard tissue trauma tended to present color change, periapical radiolucency and premature loss, whereas teeth with supporting tissue trauma showed color change, abnormal position, premature loss and periapical radiolucency as the most common sequelae. Knowledge about the predicted risks of complications may help clinicians establish appropriate treatment plans. PMID- 27556556 TI - Civil liability: characterization of the demand for lawsuits against dentists. AB - In light of the fact that dentists may be held civilly liable for their practice, it is important to understand the current situation of lawsuits filed against these professionals by studying current legal decisions and the literature. The objective of this study was to analyze the case law of the Court of Justice of Sao Paulo, Brazil, relative to the profile of patients and professionals, the most commonly involved specialties, the amounts litigated and the court decisions pertaining to civil liability lawsuits against dentists. In an inductive approach, a single researcher screened and collected civil liability rulings by accessing the Court's website, and following a statistical-descriptive procedure and an indirect observation technique. The most frequently involved specialty was prosthodontics. However, oral and maxillofacial surgery was related to a higher incidence of damages awarded to settle claims and to higher damage amounts. The dentist was found guilty in 44.32% of the cases researched. Pecuniary damages ranged between R$ 485.50 and R$ 12,530.00, and non-pecuniary damages ranged between R$ 2,500.00 and R$ 70,000.00. Most lawsuits were filed by women against male dentists. An increase in the relative number of lawsuits against companies versus individuals was observed. PMID- 27556557 TI - Evaluation of the genotoxicity and mutagenicity of Ca3SiO5-based cement. AB - Ca3SiO5 is new cement based on the composition of Portland that has been developed to have superior physicochemical and biological properties. In a clinical evaluation, the cement did not appear to have cytotoxic properties and allowed for the proliferation of pulp cells and gingival fibroblasts. However, no previous studies have evaluated the genotoxicity or the mutagenicity of Ca3SiO5in vivo. Therefore, the goal of this study is to evaluate the genotoxic and mutagenic potential of Ca3SiO5-based cement in vivo. Twenty-four male Wistar rats were divided into 3 groups (n = 8). Group A rats received subcutaneous implantation of Ca3SiO5 in the dorsum. Group B rats received a single dose of cyclophosphamide (positive control). Group C rats received subcutaneous implantation of empty tubes in the dorsum (negative control). After 24 hours, all animals were euthanized and the bone marrow of the femurs was collected for use in the comet assay and the micronucleus test. The comet assay revealed that the Ca3SiO5 group had a tail intensity of 23.57 +/- 7.70%, the cyclophosphamide group had a tail intensity of 27.43 +/- 7.40%, and the negative control group had a tail intensity of 24.75 +/- 5.55%. The average number of micronuclei was 6.25 (standard deviation, SD = 3.53) in the Ca3SiO5 group, 9.75 (SD = 2.49) in the cyclophosphamide group, and 0.75 (SD = 1.03) in the negative control group. There was an increase in the micronuclei frequency in the Ca3SiO5 group compared to that of the negative control group (p < 0.05). Our data showed that exposure to the Ca3SiO5-based cement resulted in an increase in the frequency of micronuclei, but no genotoxicity was detected according to the comet assay. PMID- 27556558 TI - Erratum: Effective method for the detection of piroxicam in human plasma using HPLC. AB - [This corrects the article doi: 10.1590/1807-3107BOR-2016.vol30.0058]. PMID- 27556559 TI - Erratum: Thickness and nanomechanical properties of protective layer formed by TiF4 varnish on enamel after erosion. AB - [This corrects the article doi: 10.1590/1807-3107BOR-2016.vol30.0075]. PMID- 27556561 TI - Preface-Prion research in perspective IV. PMID- 27556560 TI - Opposing Roles of Foliar and Glandular Trichome Volatile Components in Cultivated Nightshade Interaction with a Specialist Herbivore. AB - Plant chemistry is an important contributor to the interaction with herbivores. Here, we report on a previously unknown role for foliar and glandular trichome volatiles in their interaction with the specialist herbivore of solanaceous plants, the tomato red spider mite Tetranychus evansi. We used various bioassays and chemical analyses including coupled gas chromatography-mass spectrometry (GC/MS) and liquid chromatography coupled to quadrupole time of flight mass spectrometry (LC-QToF-MS) to investigate this interaction between cultivated African nightshades and T. evansi. We show that, whereas morphologically different cultivated African nightshade species released similar foliar volatile organic compounds (VOCs) that attracted T. evansi, VOCs released from exudates of ruptured glandular trichomes of one nightshade species influenced local defense on the leaf surface. VOCs from ruptured glandular trichomes comprising mainly saturated and unsaturated fatty acids deterred T. evansi oviposition. Of the fatty acids, the unsaturated fatty acids accounted for >40% of the oviposition deterrent activity. Our findings point to a defense strategy in a plant, based on opposing roles for volatiles released by foliar and glandular trichomes in response to attack by a specialist herbivore. PMID- 27556562 TI - A stochastic model of the bovine spongiform encephalopathy epidemic in Canada. AB - Bovine spongiform encephalopathy (BSE) appeared in the United Kingdom in the mid 1980s, and has been attributed to the use of meat and bone meal (MBM) in cattle feed contaminated with a scrapie-like agent. Import of infectious materials from a country where BSE has occurred is believed to be the major factor underlying the spread of the BSE epidemic to other countries. This study presents a new stochastic model developed to estimate risk of BSE from importation of cattle infected with the BSE agent. The model describes the propagation of the BSE agent through the Canadian cattle herd through rendering and feeding processes, following importation of cattle with infectious prions. This model was used estimate the annual number of newly infected animals each year over the period 1980-2019. Model predictions suggested that the number of BSE infections in Canada might have been approximately 40-fold greater than the actual number of clinically diagnosed cases. Under complete compliance with the 2007 ban on feeding MBM, this model further predicts that BSE is disappearing from the Canadian cattle system. A series of sensitivity analyses was also conducted to test the robustness of model predictions to alternative assumptions about factors affecting the evolution of the Canadian BSE epidemic. PMID- 27556563 TI - Applications of mathematical modeling in managing the spread of chronic wasting disease (CWD) in wild deer under alternative harvesting scenarios. AB - The application of a recently developed mathematical model for predicting the spread of chronic wasting disease (CWD) in wild deer was assessed under different scenarios where harvesting is employed in disease management. A process-based mathematical model for CWD transmission in wild deer populations was recently developed and parameterized by Al-arydah et al. (2011) to provide a scientific basis for understanding the factors that affect spread of CWD and evaluate concomitant disease-control strategies. The impact of gender on CWD transmission was shown to have a significant influence on the spread of the disease in the wild. Our model demonstrates a range of harvesting rates in which CWD is controlled and deer populations survive. However, if harvesting rates are too low, the disease remains endemic for decades. Conversely, the Canadian deer population is eradicated if harvesting rates are excessive. Future investigation includes building the model to assess the spread of CWD under different disease management scenarios. PMID- 27556564 TI - A Bayesian back-calculation method to estimate the risk of bovine spongiform encephalopathy (BSE) in Canada during the period 1996-2011. AB - Seventeen typical cases of bovine spongiform encephalopathy (BSE) were detected in Canada the period of 2003-2011. The clinical incidence of BSE was censored by early slaughter, death, or exportation of infected cattle due to the long incubation period of BSE disease. The aim of this study was to estimate the infection incidence of BSE in birth cohorts during 1996-2004 and project infection frequency through to 2007. An estimate of the number of asymptomatic infected cattle slaughtered for human consumption is also provided. The number of incident, asymptomatic cases was assumed to follow a Poisson process. A Bayesian back-calculation approach was used to project the risk of contracting BSE in those birth cohorts. Model parameters and inputs were taken from scientific literature and governmental data sources. The projected number of infected cattle in birth cohorts spanning the period 1996-2007 was 492, with median 95% credible interval 258-830. If the requirement to remove specified risk material (SRM) from cattle prior to entering the food chain was not in place, the predicted number of slaughtered infected in the human food chain from 1996-2010 was 298, with a 95% credible interval 156-500. The magnitude of the BSE epidemic in Canada for 1996 2007 birth cohorts was estimated to be approximately 28-fold higher than the number of clinical cases detected through to October 2011. Although some of those cattle were slaughtered for human consumption, the requirement of SRM removal may have prevented most of the infectious material from entering the food chain. PMID- 27556565 TI - Using expert judgments to improve chronic wasting disease risk management in Canada. AB - ABSTARCT Chronic wasting disease (CWD) is a neurodegenerative, protein misfolding disease affecting cervids in North America in epidemic proportions. While the existence of CWD has been known for more than 40 years, risk management efforts to date have not been able to curtail the spread of this condition. An expert elicitation exercise was carried out in May 2011 to obtain the views of international experts on both the etiology of CWD and possible CWD risk management strategies. This study presents the results of the following three components of the elicitation exercise: (1) expert views of the most likely scenarios for the evolution of the CWD among cervid populations in Canada, (2) ranking analyses of the importance of direct and indirect transmission routes, and (3) rating analyses of CWD control measures in farmed and wild cervids. The implications of these findings for the development of CWD risk management strategies are described in a Canadian context. PMID- 27556566 TI - Expert elicitation on the uncertainties associated with chronic wasting disease. AB - A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the "Classical Model" of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available. PMID- 27556567 TI - Long-term impacts of bovine spongiform encephalopathy on beef risk perceptions and risk attitudes in Canada. AB - In this study, the objective was to examine whether or not changes in bovine spongiform encephalopathy (BSE) concerns exert an effect on people's risk perceptions and risk attitudes regarding consuming beef in Canada, 8 years after finding the first domestic animal with BSE. Data were collected from two surveys (2071 respondents) conducted with the same respondents in 2008 and 2011 in Canada. Data on meat consumption for the same households were also available from the Nielsen Homescan panel over the period 2002 to 2009. Based on census data, the current sample is generally not representative of the Canadian population, but the sample is unique in that the same individuals responded to two surveys and there is an ability to track their evolving household purchases of beef before the first survey and between the two surveys. In essence, alterations in beef risk perceptions are significantly influenced by changes in concerns regarding (1) feed given to livestock, (2) animal diseases and BSE, (3) trust in manufacturers, the government, and farmers, and (4) demographic characteristics. There were significant differences in beef purchases across households, with alterations to their risk perceptions and risk attitudes. In conclusion, although the first domestic incident of BSE was in 2003, concerns regarding BSE are still contributing to consumers' risk perceptions but not to their risk attitudes with respect to consumption of beef in 2011. PMID- 27556568 TI - Caribou consumption in northern Canadian communities. AB - Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) found in both farmed and wild deer, elk, and moose in the United States and Canada. Surveillance efforts in North America identified the geographical distribution of the disease and mechanisms underlying distribution, although the possibility of transmission to other cervids, including caribou, and noncervids, including humans, is not well understood. Because of the documented importance of caribou (Rangifer tarandus) to human populations in the northern regions of Canada, a risk-management strategy for CWD requires an understanding of the extent of potential dietary exposure to CWD. Secondary 24-h dietary recalls conducted among Inuvialuit and Inuit in 4 communities in the Northwest Territories and Nunavut were employed in this study. Econometric demand systems were estimated to model the impacts of individual- and community-level socioeconomic characteristics on expenditures on caribou and other foods, in order to examine the households' ability to consume other foods in response to changing levels of caribou consumption. Thirty-five percent of respondents reported consuming caribou in the survey period, and caribou comprised, on average, 26% of daily dietary intake by weight, or approximately 65 g/d, across individuals in the 4 communities. Consuming caribou was also shown to exert positive impacts on dietary quality, as measured by calorie intake and dietary diversity. Communities with less access to employment, income and food stores are predicted to be constrained in their ability to obtain an adequate diet in the event of scarcity of caribou meat. PMID- 27556569 TI - Ate Complexes in Iron-Catalyzed Cross-Coupling Reactions. AB - Iron-catalyzed cross-coupling reactions have an outstanding potential for sustainable organic synthesis, but remain poorly understood mechanistically. Here, we use electrospray-ionization (ESI) mass spectrometry to identify the ionic species formed in these reactions and characterize their reactivity. Transmetalation of Fe(acac)3 (acac=acetylacetonato) with PhMgCl in THF (tetrahydrofuran) produces anionic iron ate complexes, whose nuclearity (1 to 4 Fe centers) and oxidation states (ranging from -I to +III) crucially depend on the presence of additives or ligands. Upon addition of iPrCl, formation of the heteroleptic FeIII complex [Ph3 Fe(iPr)]- is observed. Gas-phase fragmentation of this complex results in reductive elimination and release of the cross-coupling product with high selectivity. PMID- 27556570 TI - Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins. AB - The intersection of small molecular weight drugs and antibody-based therapeutics is rarely studied in large scale. Both types of agents are currently part of the cancer armamentarium. However, very little is known about how to combine them in optimal ways. Immunotoxins are antibody-toxin gene fusion proteins engineered to target cancer cells via antibody binding to surface antigens. For fusion proteins derived from Pseudomonas exotoxin (PE), potency relies on the enzymatic domain of the toxin which catalyzes the ADP-ribosylation of EF2 causing inhibition of protein synthesis leading to cell death. Candidate immunotoxins have demonstrated clear value in clinical trials but generally have not been curative as single agents. Therefore we undertook three screens to discover effective combinations that could act synergistically. From the MIPE-3 library of compounds we identified various enhancers of immunotoxin action and at least one major class of inhibitor. Follow-up experiments confirmed the screening data and suggested that immunotoxins when administered with everolimus or nilotinib exhibit favorable combinatory activity and would be candidates for preclinical development. Mechanistic studies revealed that everolimus-immunotoxin combinations acted synergistically on elements of the protein synthetic machinery, including S61 kinase and 4E-BP1 of the mTORC1 pathway. Conversely, PARP inhibitors antagonized immunotoxins and also blocked the toxicity due to native ADP-ribosylating toxins. Thus, our goal of investigating a chemical library was justified based on the identification of several approved compounds that could be developed preclinically as 'enhancers' and at least one class of mitigator to be avoided. PMID- 27556571 TI - Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging. AB - PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content. RESULTS: The T1 value, 708 +/- 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 +/- 1 mM, Spm, 13.0 +/- 4.4 mM, Cit, 64.4 +/- 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 +/- 1 mM, Spm, 13.3 +/- 4.5 mM, Cit, 34.3 +/- 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265). CONCLUSION: We have shown that it is possible to perform water referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to citrate ratios. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1232-1240. PMID- 27556572 TI - Acute effects of moderate aerobic exercise on specific aspects of executive function in different age and fitness groups: A meta-analysis. AB - Whereas a wealth of studies have investigated acute effects of moderate aerobic exercise on executive function, the roles of age, fitness, and the component of executive function in this relationship still remain unclear. Therefore, the present meta-analysis investigates exercise-induced benefits on specific aspects of executive function in different age and aerobic fitness subgroups. Based on data from 40 experimental studies, a small effect of aerobic exercise on time dependent measures (g = .35) and accuracy (g = .22) in executive function tasks was confirmed. The results further suggest that preadolescent children (g = .54) and older adults (g = .67) compared to other age groups benefit more from aerobic exercise when reaction time is considered as dependent variable. In contrast to age, aerobic fitness and the executive function component had no influence on the obtained effect sizes. Consequently, high aerobic fitness is no prerequisite for temporary improvements of the executive control system, and low- as well as high fit individuals seem to benefit from exercise in a similar way. However, a higher sensitivity of executive function to acute aerobic exercise was found in individuals undergoing developmental changes. Therefore, preadolescent children and older adults in particular might strategically use a single aerobic exercise session to prepare for a situation demanding high executive control. PMID- 27556573 TI - Prehospital Triage of Injured Older Adults: Thinking Slow Inside the Golden Hour. PMID- 27556574 TI - Demographic and clinical characteristics of diagnosed and non-diagnosed psychotic disorders in the community. AB - AIM: Retrospective studies of first-episode psychosis patients have reported that psychosis often remains untreated for some time. Yet, from clinical samples, the characteristics and number of non-diagnosed untreated psychosis patients in a community can only be estimated. Thus, this short report compares socio demographic and clinical features of diagnosed and non-diagnosed psychotic individuals assessed in the community. METHODS: Using telephone interviews, we clinically assessed 2682 community participants (aged 16-40 years) in the Canton of Bern, Switzerland, to examine the characteristics of non-diagnosed psychosis. RESULTS: Of the 41 detected psychosis patients (1.5% of the sample), 21 (54%) had already been diagnosed and treated. Non-diagnosed individuals experienced a delusional disorder (DD) (n = 10) more frequently than diagnosed individuals (n = 1), but did not differ in other socio-demographic characteristics. CONCLUSION: Further study of DD should be emphasized, along with increased awareness of the condition in primary healthcare services, as individuals with DD might present themselves for other complaints. PMID- 27556575 TI - More Dialysis Has Not Proven Much Better. AB - Patients maintained on standard three times weekly hemodialysis have a high mortality rate and a limited quality of life. Some of this illness is due to systemic diseases that have caused kidney failure, and thus may be irreversible. But we presume that imperfect replacement of normal kidney function by dialysis contributes importantly. Patients on hemodialysis are subject to fluctuations in extracellular fluid volume and inorganic ion concentrations and their plasma levels of many organic waste solutes remain very high. It is thus natural to suppose that their health could be improved by increasing the intensity of dialysis treatment. But despite a great deal of work over the past 20 years, evidence that such improvement can be obtained is generally lacking. Specific benefits can indeed be achieved. Patients who cannot control their intradialytic weight gains or plasma phosphate levels with standard therapy can benefit from extending treatment time. But we cannot promise the average patient that longer or more frequent treatment will reduce mortality or improve the quality of life. PMID- 27556576 TI - Massive parallel sequencing of solid tumours - challenges and opportunities for pathologists. AB - The role of pathologists is to provide diagnostic, prognostic and predictive data to enable clinical colleagues to manage patients optimally. Current histo/anatomical pathology is predominantly morphology-based, with the addition of biomarkers, applied largely through immunohistochemistry, fluorescence in-situ hybridization (FISH) and a limited range of polymerase chain reaction (PCR)-based molecular tests. The desire to apply genomics to the clinical care of patients has been facilitated by the human genome project and subsequently by high throughput technologies known collectively as massive parallel sequencing (MPS, also referred to as next-generation sequencing, NGS). The use of MPS to identify mutations/variants and tissue RNA expression profiles for diagnosis, prognostication and targeted therapy stratification is now a reality in many clinical specialities. If histopathologists are considered experts in solid tumour pathology, MPS potentially falls within their scope; however, it challenges our predominant morphology-based paradigm. This review summarizes and comments on the current and future state of play of MPS for the practising histopathologist. It will focus on somatic mutations in solid tumours and will challenge histopathologists to take further leadership roles in this area. PMID- 27556577 TI - Risk factors for encapsulating peritoneal sclerosis: Analysis of a 36-year experience in a University Hospital. AB - AIM: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication that occurs in peritoneal dialysis (PD) therapy. The present study aimed to identify the risk factors, especially peritonitis and biocompatible PD fluid. METHODS: The study included 703 patients who received PD between January 1980 and March 2015 at two centres. The patients were divided into two groups: those who had developed EPS (EPS group: n = 44) and those who had no documentary evidence of EPS (non-EPS group: n = 659). The independent risks of EPS were determined by univariate and multivariate logistic models. RESULTS: Encapsulating peritoneal sclerosis occurred in 44/703 (6.3%) patients between January 1980 and March 2015. In multivariate logistic models of risk factors correlated with EPS, dialysate to plasma creatinine ratio (D/P Cr) by peritoneal equilibration test (PET) and history of peritonitis were risk factors for EPS development (P < 0.01, respectively) in addition to PD duration. Especially, total duration of peritonitis, defined by period between onset and resolution of peritonitis, was an important risk factor for EPS development in patients with a history of peritonitis. Receiver operating characteristic (ROC) curve analysis revealed that cut-off point for EPS development was 36 days. Moreover, biocompatible PD fluid contributed to decreased EPS development. CONCLUSION: Both the longer duration of peritonitis and higher D/P Cr, as well as the longer PD duration, were risk factors for EPS development. Furthermore, use of biocompatible PD fluid contributed to the decrease in EPS development. PMID- 27556578 TI - Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation. AB - Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33 degrees C]) were applied. This was compared with a perfused control group (group 2) where livers (n = 5) were perfused at 37 degrees C without anti-inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group 3). During 3-day follow-up, markers of reperfusion injury, bile duct injury, and liver function were examined. Aspartate aminotransferase (AST) levels during perfusion were significantly lower in the study versus control group at 1 hour (52 +/- 6 versus 162 +/- 86 U/L; P = 0.01), 2 hours (43 +/- 5 versus 191 +/- 111 U/L; P = 0.008), and 3 hours (24 +/- 16 versus 218 +/- 121 U/L; P = 0.009). During perfusion, group 1 versus group 2 had reduced interleukin (IL) 6, tumor necrosis factor alpha, and galactosidase levels and increased IL10 levels. After transplantation, group 1 had lower AST peak levels compared with group 2 and group 3 (1400 +/- 653 versus 2097 +/- 1071 versus 1747 +/- 842 U/L; P = 0.47) without reaching significance. Bilirubin levels were significantly lower in group 1 versus group 2 at day 1 (3.6 +/- 1.5 versus 6.60 +/- 1.5 MUmol/L; P = 0.02) and 3 (2 +/- 1.1 versus 9.7 +/- 7.6 MUmol/L; P = 0.01). A trend toward decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3, and 5 hours after reperfusion in group 1 versus group 2. Only 1 early death occurred in each group (80% survival). In conclusion, addition of anti-inflammatory strategies further improves warm perfused preservation. Liver Transplantation 22 1573-1583 2016 AASLD. PMID- 27556579 TI - Accounting for host cell protein behavior in anion-exchange chromatography. AB - Host cell proteins (HCP) are a problematic set of impurities in downstream processing (DSP) as they behave most similarly to the target protein during separation. Approaching DSP with the knowledge of HCP separation behavior would be beneficial for the production of high purity recombinant biologics. Therefore, this work was aimed at characterizing the separation behavior of complex mixtures of HCP during a commonly used method: anion-exchange chromatography (AEX). An additional goal was to evaluate the performance of a statistical methodology, based on the characterization data, as a tool for predicting protein separation behavior. Aqueous two-phase partitioning followed by two-dimensional electrophoresis provided data on the three physicochemical properties most commonly exploited during DSP for each HCP: pI (isoelectric point), molecular weight, and surface hydrophobicity. The protein separation behaviors of two alternative expression host extracts (corn germ and E. coli) were characterized. A multivariate random forest (MVRF) statistical methodology was then applied to the database of characterized proteins creating a tool for predicting the AEX behavior of a mixture of proteins. The accuracy of the MVRF method was determined by calculating a root mean squared error value for each database. This measure never exceeded a value of 0.045 (fraction of protein populating each of the multiple separation fractions) for AEX. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1453-1463, 2016. PMID- 27556580 TI - Targeted CT Dose Reduction Using a Novel Dose Metric and the American College of Radiology Dose Index Registry: Application to Thoracic CT Angiography. AB - OBJECTIVE: The purpose of this article is to illustrate the use of the American College of Radiology Dose Index Registry data with a novel measurement of exposure to guide quality improvement efforts. MATERIALS AND METHODS: Using information from the Dose Index Registry report covering July through December 2012, we examined our relative ranking compared with the national median CT dose for the 20 most frequently performed examinations at our institution. The total exposure variance, defined as the difference between institutional and median national dose multiplied by the local examination frequency and expressed in units of mGy-persons, was calculated. Using this metric, two examinations were selected for investigation: pulmonary and thoracic CT angiography (CTA). Protocol modifications were implemented, and postintervention dose data were assessed from the report 1 year later. RESULTS: As indicated by size-specific dose estimates (SSDEs), the 2012 pulmonary CTA was within the national interquartile range; however, total exposure variance analysis showed that it presented the greatest opportunity for improvement on a population basis. Thoracic CTA was a top quartile examination and offered the second highest potential savings. After protocol modification, the average pulmonary CTA SSDEs decreased by 16%, for a population exposure savings of 1776 mGy-persons in the 2013 report. Average thoracic CTA SSDEs decreased by 44%, for a population exposure savings of 1050 mGy-persons. CONCLUSION: Total exposure variance analysis can increase the usefulness of Dose Index Registry data by relating per-examination dose differences to the local examination frequency. This study exhibited reduction of dose metrics for two commonly performed examinations. PMID- 27556582 TI - Percutaneous Coronary Intervention for Bifurcation: How Can We Outperform the Provisional Strategy? AB - In the era of drug-eluting stents, the provisional stenting strategy has been established as the default strategy in percutaneous coronary intervention for bifurcation lesions. However, emerging evidence shows that, in selected situations, the complex strategy of stenting both vessels regardless could reduce side-branch restenosis without penalty. In particular, the double kissing crush technique has been proven to outperform the provisional strategy and other complex strategies in randomized trials. In this review, we present the evidence comparing the 2 strategies and individual stenting techniques and discuss the roles of other optimization techniques such as final kissing balloon inflation, proximal optimization technique, intravascular ultrasonography, and optical coherence tomography. Finally, we suggest a practical approach for choosing the optimal strategy for intervention with coronary bifurcation lesions. PMID- 27556581 TI - Sex Differences and Growth-Related Adaptations in Bone Microarchitecture, Geometry, Density, and Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR-pQCT Study. AB - Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls' values were 2% greater than boys'. Boys showed 13% to 48% greater cortical and total bone area across growth. Load-to strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys' superior bone size and strength compared with girls may confer them a protective advantage. However, boys' consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. (c) 2016 American Society for Bone and Mineral Research. PMID- 27556583 TI - Wandering Pleural Mesothelial Fatty Cyst. PMID- 27556584 TI - Direct Effective Dose Calculations in Pediatric Fluoroscopy-Guided Abdominal Interventions with Rando-Alderson Phantoms - Optimization of Preset Parameter Settings. AB - OBJECTIVE: The aim of the study was to calculate the effective dose during fluoroscopy-guided pediatric interventional procedures of the liver in a phantom model before and after adjustment of preset parameters. METHODS: Organ doses were measured in three anthropomorphic Rando-Alderson phantoms representing children at various age and body weight (newborn 3.5kg, toddler 10kg, child 19kg). Collimation was performed focusing on the upper abdomen representing mock interventional radiology procedures such as percutaneous transhepatic cholangiography and drainage placement (PTCD). Fluoroscopy and digital subtraction angiography (DSA) acquisitions were performed in a posterior-anterior geometry using a state of the art flat-panel detector. Effective dose was directly measured from multiple incorporated thermoluminescent dosimeters (TLDs) using two different parameter settings. RESULTS: Effective dose values for each pediatric phantom were below 0.1mSv per minute fluoroscopy, and below 1mSv for a 1 minute DSA acquisition with a frame rate of 2 f/s. Lowering the values for the detector entrance dose enabled a reduction of the applied effective dose from 12 to 27% for fluoroscopy and 22 to 63% for DSA acquisitions. Similarly, organ doses of radiosensitive organs could be reduced by over 50%, especially when close to the primary x-ray beam. CONCLUSION: Modification of preset parameter settings enabled to decrease the effective dose for pediatric interventional procedures, as determined by effective dose calculations using dedicated pediatric Rando Alderson phantoms. PMID- 27556585 TI - Using the Generalized Index of Dissimilarity to Detect Gene-Gene Interactions in Multi-Class Phenotypes. AB - To find genetic association between complex diseases and phenotypic traits, one important procedure is conducting a joint analysis. Multifactor dimensionality reduction (MDR) is an efficient method of examining the interactions between genes in genetic association studies. It commonly assumes a dichotomous classification of the binary phenotypes. Its usual approach to determining the genomic association is to construct a confusion matrix to estimate a classification error, where a binary risk status is determined and assigned to each genotypic multifactor class. While multi-class phenotypes are commonly observed, the current MDR approach does not handle these phenotypes appropriately because the thresholds for the risk statuses may not be clear. In this study, we suggest a new method for estimating gene-gene interactions for multi-class phenotypes. Our approach adopts the index of dissimilarity (IDS) as an evaluation measure. This is analytically equivalent to the common association measure of balanced accuracy (BA) for the binary traits, while it is not required to determine the risk status for the estimation. Moreover, it is easily expandable to the generalized index of dissimilarity (GIDS), which has an explicit form that can handle any number of categories. The performance of the proposed method was compared with those of other approaches via simulation studies in which fifteen genetic models were generated with three class outcomes. A consistently better performance was observed using the proposed method. The effect of a varying number of categories was examined. The proposed method was also illustrated using real genome-wide association studies (GWAS) data from the Korean Association Resource (KARE) project. PMID- 27556588 TI - Galvanic Replacement Coupled to Seeded Growth as a Route for Shape-Controlled Synthesis of Plasmonic Nanorattles. AB - Shape-controlled synthesis of metal nanoparticles (NPs) requires mechanistic understanding toward the development of modern nanoscience and nanotechnology. We demonstrate here an unconventional shape transformation of Au@Ag core-shell NPs (nanorods and nanocubes) into octahedral nanorattles via room-temperature galvanic replacement coupled with seeded growth. The corresponding morphological and chemical transformations were investigated in three dimensions, using state of-the-art X-ray energy-dispersive spectroscopy (XEDS) tomography. The addition of a reducing agent (ascorbic acid) plays a key role in this unconventional mechanistic path, in which galvanic replacement is found to dominate initially when the shell is made of Ag, while seeded growth suppresses transmetalation when a composition of Au:Ag (~60:40) is reached in the shell, as revealed by quantitative XEDS tomography. This work not only opens new avenues toward the shape control of hollow NPs beyond the morphology of sacrificial templates, but also expands our understanding of chemical transformations in nanoscale galvanic replacement reactions. The XEDS electron tomography study presented here can be generally applied to investigate a wide range of nanoscale morphological and chemical transformations. PMID- 27556586 TI - Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge. AB - Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the "LbSapSal" vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi-challenge. Our major data indicated that immunization with "LbSapSal" is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-alpha, interleukin [IL]-12, interferon [IFN] gamma) cytokines and reduction in type II cytokines (IL-4 and TGF-beta), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after "LbSapSal" immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the "LbSapSal" vaccination is a potential tool to control the Leishmania chagasi infection. PMID- 27556587 TI - A Family of CSalphabeta Defensins and Defensin-Like Peptides from the Migratory Locust, Locusta migratoria, and Their Expression Dynamics during Mycosis and Nosemosis. AB - Insect defensins are effector components of the innate defense system. During infection, these peptides may play a role in the control of pathogens by providing protective antimicrobial barriers between epithelial cells and the hemocoel. The cDNAs encoding four defensins of the migratory locust, Locusta migratoria, designated LmDEF 1, 3-5, were identified for the first time by transcriptome-targeted analysis. Three of the members of this CSalphabeta defensin family, LmDEF 1, 3, and 5, were detected in locust tissues. The pro regions of their sequences have little-shared identities with other insect defensins, though the predicted mature peptides align well with other insect defensins. Phylogenetic analysis indicates a completely novel position of both LmDEF 1 and 3, compared to defensins from hymenopterans. The expression patterns of the genes encoding LmDEFs in the fat body and salivary glands were studied in response to immune-challenge by the microsporidian pathogen Nosema locustae and the fungus Metarhizium anisopliae after feeding or topical application, respectively. Focusing on Nosema-induced immunity, qRT-PCR was employed to quantify the transcript levels of LmDEFs. A higher transcript abundance of LmDEF5 was distributed more or less uniformly throughout the fat body along time. A very low baseline transcription of both LmDEFs 1 and 3 in naive insects was indicated, and that transcription increases with time or is latent in the fat body or salivary glands of infected nymphs. In the salivary glands, expression of LmDEF3 was 20-40-times higher than in the fat body post-microbial infection. A very low expression of LmDEF3 could be detected in the fat body, but eventually increased with time up to a maximum at day 15. Delayed induction of transcription of these peptides in the fat body and salivary glands 5-15 days post-activation and the differential expression patterns suggest that the fat body/salivary glands of this species are active in the immune response against pathogens. The ability of N. locustae to induce salivary glands as well as fat body expression of defensins raises the possibility that these AMPs might play a key role in the development and/or tolerance of parasitic infections. PMID- 27556589 TI - Sex and Catheter Ablation for Ventricular Tachycardia: An International Ventricular Tachycardia Ablation Center Collaborative Group Study. AB - Importance: Significant differences have been described between women and men regarding presentation, mechanism, and treatment outcome of certain arrhythmias. Previous studies of ventricular tachycardia (VT) ablation have not included sufficient women for meaningful comparison. Objective: To compare outcomes between women and men with structural heart disease undergoing VT ablation. Design, Setting, and Participants: Investigator-initiated, multicenter, observational study performed between 2002 and 2013, conducted by the International VT Ablation Center Collaborative Group, consisting of 12 high volume ablation centers. Consecutive patients with structural heart disease undergoing VT ablation were studied. Structural heart disease was defined as left ventricular ejection fraction less than 55%, hypertrophic cardiomyopathy, or right ventricular cardiomyopathy, with scar confirmed during electroanatomic mapping. Exposures: Catheter ablation. Main Outcomes and Measures: Ventricular tachycardia-free survival and transplant-free survival were compared between women and men. Cox proportional hazard modeling was performed. Results: Of 2062 patients undergoing ablation, 266 (12.9%) were women. Mean (SD) age was 62.4 (13.3) years and 1095 (53.1%) had ischemic cardiomyopathy. Compared with men, women were younger, with higher left ventricular ejection fraction and less VT storm. Despite this, women had higher rates of 1-year VT recurrence following ablation (30.5% vs 25.3%; P = .03). This difference was only partially explained by higher prevalence of nonischemic cardiomyopathy among women and was actually most pronounced among those with ischemic cardiomyopathy. Conclusions and Relevance: In 12 high-volume ablation centers, women with structural heart disease have worse VT-free survival following ablation than men. Whether this is owing to differences in referral pattern, arrhythmia substrate, or undertreatment requires further study. PMID- 27556590 TI - Acute Cholangitis Management: Prevention of Organ Failure and Death. PMID- 27556591 TI - A Systematic Investigation on CrCun Clusters with n = 9-16: Noble Gas and Tunable Magnetic Property. AB - A systematic investigation on structure, dissociation behavior, chemical bonding, and magnetic property of Cr-doped Cun clusters (n = 9-16) is carried out using the mean of density functional theory calculations. It is found that CrCu12 is a crucial size, preferring an icosahedral Cu12 cage with the central Cr dopant. Smaller cluster sizes appear as on the way to form the CrCu12 icosahedron while larger ones are produced by attaching additional Cu atoms to the CrCu12 core. The presence of Cr dopant obviously enhances the stability of CrCun clusters in comparison to that of pure counterparts. Exceptionally stable CrCu12 has an 18 electron closed-shell electronic structure, mimicking a noble gas in the viewpoint of superatom concept. Analysis on cluster electronic structure shows that the interplay between 3d orbitals of Cr and 4s orbitals of Cu has a vital role on the magnetic properties of CrCun clusters. PMID- 27556592 TI - Laser Treatment of Nanoparticulated Metal Thin Films for Ceramic Tile Decoration. AB - This paper presents a new method for the fabrication of metal-like decorative layers on glazed ceramic tiles. It consists of the laser treatment of Cu thin films prepared by electron-beam evaporation at glancing angles. A thin film of discontinuous Cu nanoparticles was electron-beam-evaporated in an oblique angle configuration onto ceramic tiles and an ample palette of colors obtained by laser treatment both in air and in vacuum. Scanning electron microscopy along with UV vis-near-IR spectroscopy and time-of-flight secondary ion mass spectrometry analysis were used to characterize the differently colored layers. On the basis of these analyses, color development has been accounted for by a simple model considering surface melting phenomena and different microstructural and chemical transformations of the outmost surface layers of the samples. PMID- 27556594 TI - Reflection of Socioeconomic Changes in Wastewater: Licit and Illicit Drug Use Patterns. AB - The economic crisis plaguing Greece was expected to impact consumption of pharmaceuticals and illicit drugs - a priori to an unknown extent. We quantified the change of use for various classes of licit and illicit drugs by monitoring Athens' wastewater from 2010 to 2014. A high increase in the use of psychoactive drugs was detected between 2010 and 2014, especially for antipsychotics (35 fold), benzodiazepines (19-fold), and antidepressants (11-fold). This directly reflects the perceived increase of incidences associated with mental illnesses in the population, as a consequence of severe socioeconomic changes. Other therapeutic classes, like antiepileptics, hypertensives, and gastric and ulcer drugs also showed an increase in use (from 2-fold increase for antiepileptics to 13-fold for hypertensives). In contrast, the overall use of antibiotics and NSAIDs decreased. For mefenamic acid, an almost 28-fold decrease was observed. This finding is likely related to the reduction in drug expenditure applied in public health. A 2-fold increase of methamphetamine use was detected, associated with a cheap street drug called "sisa" (related to marginal conducts), which is a health concern. MDMA (5-fold) and methadone (7-fold) use showed also an increase, while cocaine and cannabis estimates did not show a clear trend. PMID- 27556593 TI - Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial. AB - IMPORTANCE: Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long term use. OBJECTIVE: To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. DESIGN, SETTING, AND PARTICIPANTS: A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. INTERVENTIONS: Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. MAIN OUTCOMES AND MEASURES: The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. RESULTS: Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to 1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P = .005). CONCLUSIONS AND RELEVANCE: Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01825798. PMID- 27556595 TI - pH and Salt Effects on Surface Activity and Self-Assembly of Copolymers Containing a Weak Polybase. AB - Copolymers with well-defined architectures, controlled molecular weights, and narrow molar mass dispersities (D) were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The resultant polymers contain different combinations of the pH-responsive monomer 2-(diethylaminoethyl) methacrylate (DEAEMA), the hydrophobic comonomer butyl methacrylate (BMA), and a neutral hydrophilic stabilizing monomer polyethylene glycol monomethyl ether methacrylate (designated O950). Surface tension and cryo-TEM measurements of native and heavy-atom stained samples were used to characterize the pH and salt responsiveness of the different polymers as a function of their composition. These studies indicate that while the polymers predominately self-assemble to form spherical micelles, a narrow size distribution is observed in aqueous solutions of poly(O950)-b-(BMA) and poly(O950)-b-(DEAEMA-co-BMA), whereas a broad size distribution characterizes the assemblies of poly(O950)-b-(DEAEMA) and poly(DEAEMA-co-BMA). In the latter case, micelles having diameters around 15-25 nm are found along with smaller aggregates (about 10 nm) mostly arranged in elongated necklace-like structures. The pH and salt-responsiveness of the DEAEMA residue, as indicated by the surface activity of the copolymers, was found to depend on the nature of the additional components: covalently linked hydrophobic groups (BMA) moderated the pH response of the copolymer as compared to nonionic and hydrophilic groups as in poly(O950)-b-(DEAEMA). These results suggest that mutual interactions among the building blocks of self-assembling copolymers should be taken into account when designing responsive copolymers. PMID- 27556596 TI - Transareolar Single-Port Needlescopic Thoracic Sympathectomy Under Intravenous Anesthesia Without Intubation: A Randomized Controlled Trial. AB - OBJECTIVES: Transareolar single-port needlescopic thoracic sympathectomy under intravenous anesthesia without intubation has rarely been attempted in managing primary palmar hyperhidrosis (PPH). The objective of this study is to evaluate the feasibility and safety of this minimally invasive technique. MATERIALS AND METHODS: From May 2012 to May 2015, 168 male patients with severe PPH underwent single-port endoscopic thoracic sympathectomy (ETS) and were randomly allocated to groups A or B. Patients in group A underwent nonintubated transareolar ETS with a 2-mm needle endoscope, while those in group B underwent intubated transaxillary ETS with a 5-mm thoracoscope. RESULTS: All procedures were performed successfully. The palms of all patients became dry and warm immediately after surgery. The mean resuscitation time was significantly shorter in nonintubated patients than in intubated patients. Postoperative sore throat occurred in 4 patients in group A and in 32 patients in group B (P < .01). The mean incision length was significantly shorter in group A than in group B. The mean postoperative pain scores were markedly higher in group B than in group A. The mean cost of anesthesia was considerably lower in nonintubated patients than in intubated patients. The mean cosmetic scores were higher in group A than in group B (P < .01). CONCLUSIONS: Nonintubated transareolar single-port ETS with a needle endoscope is a safe, effective, and minimally invasive therapeutic procedure, which allows a smaller incision with less pain and excellent cosmetic results. This novel procedure can be performed in a routine clinical practice for male patients with severe PPH. PMID- 27556597 TI - A hierarchical model for clustering m(6)A methylation peaks in MeRIP-seq data. AB - BACKGROUND: The recent advent of the state-of-art high throughput sequencing technology, known as Methylated RNA Immunoprecipitation combined with RNA sequencing (MeRIP-seq) revolutionizes the area of mRNA epigenetics and enables the biologists and biomedical researchers to have a global view of N (6) Methyladenosine (m(6)A) on transcriptome. Yet there is a significant need for new computation tools for processing and analysing MeRIP-Seq data to gain a further insight into the function and m(6)A mRNA methylation. RESULTS: We developed a novel algorithm and an open source R package ( http://compgenomics.utsa.edu/metcluster ) for uncovering the potential types of m(6)A methylation by clustering the degree of m(6)A methylation peaks in MeRIP Seq data. This algorithm utilizes a hierarchical graphical model to model the reads account variance and the underlying clusters of the methylation peaks. Rigorous statistical inference is performed to estimate the model parameter and detect the number of clusters. MeTCluster is evaluated on both simulated and real MeRIP-seq datasets and the results demonstrate its high accuracy in characterizing the clusters of methylation peaks. Our algorithm was applied to two different sets of real MeRIP-seq datasets and reveals a novel pattern that methylation peaks with less peak enrichment tend to clustered in the 5' end of both in both mRNAs and lncRNAs, whereas those with higher peak enrichment are more likely to be distributed in CDS and towards the 3'end of mRNAs and lncRNAs. This result might suggest that m(6)A's functions could be location specific. CONCLUSIONS: In this paper, a novel hierarchical graphical model based algorithm was developed for clustering the enrichment of methylation peaks in MeRIP-seq data. MeTCluster is written in R and is publicly available. PMID- 27556598 TI - A Computerized Cognitive Assessment Method in a Nurse-Led Clinic: A Comparative Study With the Traditional Pencil-and-Paper Approach. AB - This article reports our experience in developing a computerized cognitive assessment method in a nurse-led clinic. The assessment and report-writing time and the accuracy of using a computer as an assessment medium were compared with assessments that use the traditional pencil-and-paper method. The attitudes of professionals and service users toward the computerized approach were also collected. The results found that the computerized approach not only helped to reduce the time spent making assessments and writing reports but also improved the accuracy of the assessment when compared with the pencil-and-paper method. Most of the professionals and service users who were interviewed responded positively toward computerized assessments. The experience gained in this study will also help us to standardize our assessment procedures, promote communication among members of the clinical team, and facilitate data management and clinical research. PMID- 27556599 TI - Is Single-Stage Prosthetic Reconstruction Cost Effective? A Cost-Utility Analysis for the Use of Direct-to-Implant Breast Reconstruction Relative to Expander Implant Reconstruction in Postmastectomy Patients. AB - BACKGROUND: Prosthetic breast reconstruction is most commonly performed using the two-stage (expander-implant) technique. However, with the advent of skin-sparing mastectomy and the use of acellular dermal matrices, one-stage prosthetic reconstruction has become more feasible. Prior studies have suggested that one stage reconstruction has economic advantages relative to two-stage reconstruction despite a higher revision rate. This is the first cost-utility analysis to compare the cost and quality of life of both procedures to guide patient care. METHODS: A comprehensive literature review was conducted using the MEDLINE, EMBASE, and Cochrane databases to include studies directly comparing matched patient cohorts undergoing single-stage or staged prosthetic reconstruction. Six studies were selected examining 791 direct-to-implant reconstructions and 1142 expander-implant reconstructions. Costs were derived adopting both patient and third-party payer perspectives. Utilities were derived by surveying an expert panel. Probabilities of clinically relevant complications were combined with cost and utility estimates to fit into a decision tree analysis. RESULTS: The overall complication rate was 35 percent for single-stage reconstruction and 34 percent for expander-implant reconstruction. The authors' baseline analysis using Medicare reimbursement revealed a cost decrease of $525.25 and a clinical benefit of 0.89 quality-adjusted life-year when performing single-stage reconstructions, yielding a negative incremental cost-utility ratio. When using national billing, the incremental cost-utility further decreased, indicating that direct-to-implant breast reconstruction was the dominant strategy. Sensitivity analysis confirmed the robustness of the authors' conclusions. CONCLUSIONS: Direct-to-implant breast reconstruction is the dominant strategy when used appropriately. Surgeons are encouraged to consider single-stage reconstruction when feasible in properly selected patients. PMID- 27556600 TI - Does the Use of Incisional Negative-Pressure Wound Therapy Prevent Mastectomy Flap Necrosis in Immediate Expander-Based Breast Reconstruction? AB - BACKGROUND: Mastectomy flap necrosis is one of the most common and significant complications in immediate expander-based breast reconstruction. Negative pressure wound therapy is widely used for open wounds but is not commonly used for closed incisional wounds. However, the postoperative use of incisional negative-pressure wound therapy is demonstrated to reduce complication rates. The authors evaluate the incidence of mastectomy flap necrosis in patients with incisional negative-pressure wound therapy after immediate expander-based breast reconstruction compared with the incidence in patients with conventional dressing. METHODS: A retrospective review was conducted to identify patients who underwent immediate expander-based breast reconstruction between January of 2010 and February of 2015 at a single institution. Patients were divided into a conventional dressing group and an incisional negative-pressure wound therapy group. Patient demographics, intraoperative findings, and complications were compared between the two groups. RESULTS: A total of 228 breasts (206 patients) were included in this study. Of these, the incisional negative-pressure wound therapy group included 45 breasts (44 patients) and the conventional dressing group included 183 breasts (162 patients). The incisional negative-pressure wound therapy group had a lower overall complication rate (11.1 percent versus 27.9 percent; p = 0.019), overall mastectomy flap necrosis rate (8.9 percent versus 23.5 percent; p = 0.030), and major mastectomy flap necrosis rate (2.2 percent versus 13.7 percent; p = 0.031) compared with the conventional dressing group. CONCLUSIONS: Incisional negative-pressure wound therapy reduced the incidence of mastectomy flap necrosis. This simple and reliable dressing technique can be effective in preventing mastectomy flap necrosis in immediate expander-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27556601 TI - Discussion: Does the Use of Incisional Negative-Pressure Wound Therapy Prevent Mastectomy Flap Necrosis in Immediate Expander-Based Breast Reconstruction? PMID- 27556602 TI - The Subtleties of Success in Simultaneous Augmentation-Mastopexy. AB - BACKGROUND: Many have challenged the safety of performing breast augmentation and mastopexy simultaneously. However, staging these procedures incurs the increased risk and inconvenience of two periods of anesthesia and recuperation. The authors set out to evaluate the occurrence of complications across the populations of patients undergoing (1) combined augmentation-mastopexy, (2) isolated augmentation, and (3) isolated mastopexy. METHODS: A retrospective analysis of one surgeon's consecutive series of each of these procedures from 2000 to 2009 was conducted. Preoperative risk factors were characterized. Sixteen different complications were examined, and those necessitating operative revision were tracked. Statistical analysis was performed looking for significant differences between the surgical groups. RESULTS: No instances of infection, tissue loss, or implant exposure occurred among the 297 patients over an average follow-up period of 15.5 months. The isolated mastopexy group did not provide sufficient data for statistical comparison. Tissue-related complications were most common in the combined procedure group. The operative revision rate for isolated augmentation was 7.97 percent compared with a combined procedure revision rate of 12.4 percent (p = 0.28). CONCLUSIONS: The majority of complications in this series comparing simultaneous augmentation-mastopexy to isolated augmentation were minor. Complications requiring operative revision were not found to be significantly different between the two groups. There was a much lower reoperation rate (12.4 percent) with the combined procedure compared with a 100 percent reoperation rate when the procedure is staged. Thus, the authors feel the combined procedure can safely be part of every plastic surgeon's practice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27556603 TI - Phalloplasty: A Review of Techniques and Outcomes. AB - BACKGROUND: Acquired or congenital absence of the penis can lead to severe physical limitations and psychological outcomes. Phallic reconstruction can restore various functional aspects of the penis and reduce psychosocial sequelae. Moreover, some female-to-male transsexuals desire creation of a phallus as part of their gender transition. Because of the complexity of phalloplasty, there is not an ideal technique for every patient. This review sets out to identify and critically appraise the current literature on phalloplasty techniques and outcomes. METHODS: A comprehensive literature search of the MEDLINE, PubMed, and Google Scholar databases was conducted for studies published through July of 2015 with multiple search terms related to phalloplasty. Data on techniques, outcomes, complications, and patient satisfaction were collected. RESULTS: A total of 248 articles were selected and reviewed from the 790 identified. Articles covered a variety of techniques on phalloplasty. Three thousand two hundred thirty-eight patients underwent phalloplasty, with a total of 1753 complications reported, although many articles did not explicitly comment on complications. One hundred four patients underwent penile replantation and two underwent penile transplantation. Satisfaction was high, although most studies did not use validated or quantified approaches to address satisfaction. CONCLUSIONS: Phalloplasty techniques are evolving to include a number of different flaps, and most techniques have high reported satisfaction rates. Penile replantation and transplantation are also options for amputation or loss of phallus. Further studies are required to better compare different techniques to more robustly establish best practices. However, based on these studies, it appears that phalloplasty is highly efficacious and beneficial to patients. PMID- 27556604 TI - Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model. AB - BACKGROUND: Previous studies on solid organ transplantation have shown that cold ischemia contributes to the development of chronic allograft vasculopathy. The authors evaluated the effect of cold ischemia on the development of chronic rejection in vascularized composite allotransplantation. METHODS: Thirty rat hindlimbs were transplanted and divided into two experimental groups: immediate transplantation and transplantation after 7 hours of cold ischemia. The animals received daily low-dose immunosuppression with cyclosporine A for 2 months. Intimal proliferation, arterial permeability rate, leukocyte infiltration, and tissue fibrosis were assessed. The CD3, CD4, CD8, CD20, and CD68 cells per microscopic field (200*) were counted, and C4d deposition was investigated. Cytokine RNA analysis was performed to measure tumor necrosis factor-alpha, interleukin-6, and interleukin-10 levels. RESULTS: Significant differences were found in the intimal proliferation and arterial permeability rate between the two groups (p = 0.004). The arterial permeability rate worsened in the most distal and small vessels (p = 0.047). The numbers of CD3, CD8, CD20, and CD68 were also statistically higher in the cold ischemia group (p < 0.05, all levels). A trend toward significance was observed with C4d deposition (p = 0.059). No differences were found in the RNA of cytokines. CONCLUSIONS: An association between cold ischemia and chronic rejection was observed in experimental vascularized composite allotransplantation. Chronic rejection intensity and distal progression were significantly related with cold ischemia. The leukocyte infiltrates in vascularized composite allotransplantation components were a rejection marker; however, their exact implication in monitoring and their relation with cold ischemia are yet to be clarified. PMID- 27556605 TI - Predictors of Patient Satisfaction with Hand Function after Fasciectomy for Dupuytren's Contracture. AB - BACKGROUND: This study examined patient satisfaction with hand function after fasciectomy for Dupuytren's contracture and determined which preoperative patient and disease-specific factors predicted this satisfaction. METHODS: Demographics and disease-specific factors were assessed from a prospective cohort of 194 patients who completed the Michigan Hand Outcomes Questionnaire preoperatively and underwent limited fasciectomy between 2011 and 2014 at six hand surgery practice sites. To evaluate satisfaction with hand function, patients were asked to complete the Michigan Hand Outcomes Questionnaire during the first year after fasciectomy. After patients were classified into a satisfied and an unsatisfied category using the question that specifically pertains to satisfaction with hand function, the authors applied multivariate logistic regression modeling to identify independent predictors of patient satisfaction. RESULTS: At an average of 10 months (range, 6 to 12 months) after fasciectomy, 84 percent (n = 163) of the patients were satisfied with their hand function. In multivariate analyses adjusting for the degree of postoperative residual contracture (p < 0.001) and complications (p < 0.001), a higher preoperative Michigan Hand Outcomes Questionnaire hand appearance subscore and male gender predicted a higher likelihood of becoming satisfied after fasciectomy. Other patient- and disease specific factors did not show evidence for an association with patient satisfaction. CONCLUSIONS: The findings of this study suggest that providers should consider assessing concerns about the appearance of the hand in patients with Dupuytren's contracture. They also highlight the importance of complication prevention and full contracture correction from the patient's perspective. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. PMID- 27556606 TI - Evaluating the Rule of 10s in Cleft Lip Repair: Do Data Support Dogma? AB - BACKGROUND: Cleft lip represents one of the most common birth defects in the world. Although the timing of cleft lip repair is contingent on a number of factors, the "rule of 10s" remains a frequently quoted safety benchmark. Initially reported by Wilhelmsen and Musgrave in 1966 and modified by Millard in 1976, this rule referred to performing surgery once patients had reached cutoffs in weight, hemoglobin, and age/leukocyte count. Despite significant advances in both surgical and anesthetic technique, the oft-quoted "rule of 10s" has not been systematically investigated since its inception. METHODS: Patients who underwent primary cleft lip repair were identified from the National Surgical Quality Improvement Program Pediatric database. Multivariate logistic regression models were used to determine the independent effect of each rule of 10 metric or violation of the rule of 10s as a whole on postoperative complications, and to determine independent risk factors for complications in cleft lip surgery. RESULTS: One thousand three hundred thirteen patients met inclusion criteria, with a 3.6 percent complication rate. Of the included patients, 151 (11.5 percent) violated at least one facet of the rule of 10s. Other than patient weight, neither the rule of 10s nor any individual metric was significantly predictive of postoperative complications. CONCLUSIONS: Since its introduction nearly a half century ago, the risks associated with performing surgery in patients who violate the rule of 10s has undergone dramatic reductions. This analysis highlights the need to continually validate and evaluate dogma as the field continues to advance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. PMID- 27556607 TI - In-Depth Review of Symptoms, Triggers, and Surgical Deactivation of Frontal Migraine Headaches (Site I). AB - BACKGROUND: This study reports details of the technique and assesses efficacy of surgical deactivation of frontal migraine headaches. In addition, this study examines the effect of surgical deactivation of frontal migraine headaches on migraine triggers and associated symptoms besides the pain. METHODS: Charts of 270 patients undergoing surgery performed by a single surgeon for frontal migraine headaches, who were followed for at least 1 year, were analyzed. Median regression adjusted for age, sex, and follow-up time was used to determine postoperative reduction in frontal-specific Migraine Headache Index, which is the product of duration, frequency, and severity. Reduction in migraine-days, which is the product of duration and frequency, was also measured. The association between individual symptom or trigger resolution and frontal-specific Migraine Headache Index reduction was studied by logistic regression. Details of the surgical treatment are discussed and complication rates are reported. RESULTS: Eighty-six percent of patients reported a successful operation (>=50 percent improvement of frontal-specific Migraine Headache Index) at least 12 months after surgery (mean follow-up, 3 years). Eighty-four percent of patients had a successful operation as measured by migraine-days. Fifty-seven percent of patients reported complete elimination of frontal migraine headaches. Symptoms resolving with successful site I surgery beyond the headaches include visual aura and blurred or double vision (p < 0.05). Triggers resolving with successful site I surgery include fatigue, weather change, and missed meals (p < 0.05). CONCLUSIONS: Surgical deactivation of frontal migraine headaches provides long lasting migraine relief. Successful site I surgery is associated with changes in specific symptoms and triggers. This information can assist in trigger avoidance and contribute to constellations used for frontal migraine headache trigger-site identification. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27556608 TI - Discussion: Suprafascial Anterolateral Thigh Flap Harvest: A Better Way to Minimize Donor-Site Morbidity in Head and Neck Reconstruction. PMID- 27556609 TI - Melting the Plastic Ceiling: Overcoming Obstacles to Foster Leadership in Women Plastic Surgeons. AB - The underrepresentation of women leaders in plastic surgery echoes a phenomenon throughout society. The importance of female leadership is presented, and barriers to gender equality in plastic surgery, both intrinsic and extrinsic, are discussed. Strategies for fostering women in leadership on an individual level and for the specialty of plastic surgery are presented. PMID- 27556610 TI - Women and Men in Plastic Surgery: How They Differ and Why It Matters. PMID- 27556613 TI - The Telemark Breast Score: A Reliable Method for the Evaluation of Results after Breast Surgery. AB - BACKGROUND: Validated instruments for assessing results after breast surgery are sparse. The authors present here a method used for the past 10 years at their institution for evaluation of outcome after breast-conserving surgery and microsurgical breast reconstruction. METHODS: The Telemark Breast Score is a method based on standard two-dimensional photographs assessing the outcome after breast surgery in terms of volume, shape, and symmetry. Three panels comprising two plastic surgeons, two breast surgeons, and two nurses tested the Telemark Breast Score on 346 patients who underwent breast-conserving surgery for cancer and 31 other patients who underwent deep inferior epigastric perforator flap reconstruction. All patients were assessed at least 1 year after their operation. Consistency of agreement between and within the panels was studied. RESULTS: Interobserver and intraobserver reliability was good after consensus discussion. Good rating stability was shown using test-retest measurements. CONCLUSION: The Telemark Breast Score is an inexpensive, statistically reliable method and can be applied for quality control after breast surgery. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27556614 TI - Comparing the Outcomes of Different Agents to Treat Vasospasm at Microsurgical Anastomosis during the Papaverine Shortage. AB - BACKGROUND: Papaverine remains popular for treating intraoperative vasospasm, but the recent shortage has forced surgeons to trial antispasmodic agents unproven in microsurgery but commonly used in other body areas. During this shortage, the authors have used topical lidocaine and nicardipine to break intraoperative vasospasm. This study aims to analyze the outcomes of these medications on flap complications compared with papaverine. METHODS: All consecutive free flaps performed for breast reconstruction at a single institution were reviewed. Data collected included patient demographics, comorbidities, complications, and type of antispasmodic agent. Rates of reexploration, complications, and flap salvage were compared between patients receiving antispasmodic agents and matched papaverine controls. RESULTS: Of the 1087 flaps treated with antispasmodic agents, nicardipine was used on 59 flaps and lidocaine was used on 55 flaps. Patients treated with lidocaine had higher body mass indexes (31.0 kg/m versus 27.4 kg/m; p = 0.001). Patients treated with nicardipine tended to be older (64.0 versus 48.5; p < 0.01) and have a history of hypertension (22.0 percent versus 10.4 percent; p = 0.08) or preoperative irradiation (32.2 percent versus 13.6 percent; p = 0.016) compared with papaverine controls. No differences in the rates of total or partial flap loss, unplanned return to the operating room, or fat necrosis were observed between any of the groups. However, the nicardipine group demonstrated a higher rate of infection (15.3 percent versus 3.4 percent; p = 0.027). CONCLUSION: Substituting lidocaine or nicardipine for papaverine to treat vasospasm did not demonstrate an increased rate of flap loss or return to the operating room, making these medications safe and efficacious alternatives to papaverine. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27556615 TI - Computed Tomographic Angiography-Based Planning of Bipedicled DIEP Flaps with Intraflap Crossover Anastomosis: An Anatomical and Clinical Study. AB - BACKGROUND: When using deep inferior epigastric artery perforator (DIEP) flaps in breast reconstruction, harvesting bipedicled flaps can be a valuable option in cases requiring the transfer of a large portion of harvested flaps. Connecting the bilateral deep inferior epigastric arteries (DIEAs) by intraflap crossover anastomosis is one of the most popular methods of constructing bipedicled DIEP flaps. Planning the primary and secondary pedicle configurations for reliable intraflap crossover anastomosis is crucial. To achieve this, detailed anatomical DIEA information might be helpful. However, meticulous planning of bipedicled DIEP flaps based on computed tomographic angiography has not been reported. METHODS: Detailed anatomical investigation of DIEA branches was conducted using computed tomographic angiographs of 100 hemiabdomens. Thirty-eight prospectively collected patients who underwent breast reconstruction using bipedicled DIEP flaps with intraflap crossover under computed tomographic angiography-based planning were reviewed. RESULTS: Three intramuscular DIEA branching patterns with distinct branch point topography, branch diameters, and superior continuations cranial to sizable perforators were observed. In the prospective clinical study, a primary pedicle with a recipient branch for intraflap crossover anastomosis could be specified preoperatively using computed tomographic angiography-based anatomical data of the pedicles, including size of DIEA branches or their superior continuation and size of perforators. In all cases, the bipedicle configuration was easily achieved as planned on computed tomographic angiography, and secure perfusion of the entire flap was achieved. CONCLUSIONS: The authors' results suggest that computed tomographic angiography provides detailed anatomical DIEA information, and comprehensive analysis of these data allows precise planning of bipedicle configurations with intraflap crossover anastomosis in DIEP flaps. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27556616 TI - Inferior Turbinate Hypertrophy in Rhinoplasty: Systematic Review of Surgical Techniques. AB - BACKGROUND: Inferior turbinate hypertrophy is often encountered by plastic surgeons who perform rhinoplasty. Many treatment options are available to treat the inferior turbinate. The objective of this study was to systematically review outcomes of available techniques and provide guidance to surgical turbinate management. METHODS: A MEDLINE search was performed for means of treating inferior turbinate hypertrophy. Studies selected focused on treatment of the inferior turbinate in isolation and excluding patients with refractory allergic rhinitis, vasomotor rhinitis, or hypertrophic rhinitis. RESULTS: Fifty-eight articles were identified, collectively including the following surgical treatments of inferior turbinate hypertrophy: total turbinectomy, partial turbinectomy, submucosal resection, laser surgery, cryotherapy, electrocautery, radiofrequency ablation, and turbinate outfracture. Outcomes and complications were collected from all studies. Procedures such as turbinectomy (partial/total) and submucosal resection showed crusting and epistaxis at comparatively higher rates, whereas more conservative treatments such as cryotherapy and submucous diathermy failed to provide long-term results. Submucosal resection and radiofrequency ablation were shown to decrease nasal resistance and preserve mucosal function. No literature exists to support the belief that turbinate outfracture alone is an effective treatment for turbinate hypertrophy. CONCLUSIONS: Treatment of inferior turbinate hypertrophy is best accomplished with modalities that provide long-lasting results, preservation of turbinate function, and low complication rates. Submucosal resection and radiofrequency ablation appear to best fulfill these criteria. Turbinate outfracture should only be considered in combination with tissue-reduction procedures. PMID- 27556617 TI - Topographic Anatomy of the Inferior Medial Palpebral Artery and Its Relevance to the Pretarsal Roll Augmentation. AB - BACKGROUND: A detailed analysis of the topography of the inferior medial palpebral artery is needed to optimize the safety and efficacy of pretarsal roll augmentation. METHODS: Thirty-one hemifaces from 13 Korean and 8 Thai cadavers (15 male and six female cadavers) were dissected. The distributions of the inferior medial palpebral artery were determined with respect to the superior medial palpebral artery and the supratrochlear artery. RESULTS: Four distribution patterns were observed. The inferior and superior medial palpebral arteries branched individually from the ophthalmic artery, with the ophthalmic artery terminating as the supratrochlear artery on the forehead (type I); a short trunk branched from the ophthalmic artery and divided into the inferior medial palpebral artery and superior medial palpebral artery, and the ophthalmic artery terminated as the supratrochlear artery (type II); the inferior and superior medial palpebral arteries arose together from the ophthalmic artery, and the ophthalmic artery terminated as the supratrochlear artery (type III); or the inferior and superior medial palpebral arteries were the terminal branches of the ophthalmic artery, with the supratrochlear artery arising from the angular artery (type IV). The diameter of the artery was 0.94 +/- 0.22 mm at the entry point and 0.37 +/- 0.11 mm at the lateral canthus. CONCLUSIONS: The inferior medial palpebral artery was located along the tarsal plate deep to the pretarsal part of the orbicularis oculi in the lower eyelid. Injections to augment the pretarsal roll should be made between the subcutaneous tissue and this pretarsal part of the orbicularis oculi. PMID- 27556618 TI - Fat Grafting for Gluteal Augmentation: A Systematic Review of the Literature and Meta-Analysis. AB - BACKGROUND: With the increasing demand for gluteal fat augmentation, reports of fatal complications have surfaced. Therefore, the authors proposed to analyze the published techniques and compare different protocols, to identify those of potential concern. METHODS: A systematic review of the literature was performed with a search of 21 terms on the PubMed, MEDLINE, Cochrane, and Scientific Electronic Library Online databases. Nineteen articles meeting our predetermined criteria were analyzed, and data from the different steps of the procedure were classified, allowing evaluation and comparison of techniques. Independent-samples t test and one-way analysis of variance were used for statistical analysis. RESULTS: Seventeen case series and two retrospective studies including 4105 patients were reviewed. Most articles were authored in Colombia, Mexico, and Brazil. Most procedures were performed on adult female patients under general anesthesia. Fat was harvested using a tumescent technique from the lower extremities and the back, with machine-vacuum suction. A mean of 400 ml of decanted lipoaspirate was injected into each gluteal region, mostly subcutaneously and intramuscularly with 60-ml syringes. Most patients rated their results as "excellent." The mean complication rate was 7 percent (6.7 percent minor, 0.32 percent major), with no significant relation to the planes of injection. CONCLUSIONS: Fat grafting is an effective and predictable way to remodel the gluteal region; however, the procedure is not without risks. Avoiding gluteal vessel damage may prevent most feared complications, such as fat embolism. Accurate analysis, systematization of the procedure, and reporting cases in the fat grafting registry may provide the foundation for optimization of outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27556619 TI - Liposuction-Assisted Short-Scar Brachioplasty: Technical Highlights. AB - Upper arm contouring is based on the location and amount of excess skin and fat. The short-scar brachioplasty addresses minimal to moderate skin laxity and lipodystrophy in the proximal arm in patients with appropriate skin tone and quality. This article highlights technical refinements of the senior author's (R.J.R.) approach to short-scar medial liposuction-assisted brachioplasty to maximize results and minimize incision length. To highlight this simple and safe approach with high patient/surgeon satisfaction, the authors discuss the following in this Video Plus article: patient examination, preoperative assessment, surgical pearls, and postoperative outcomes. PMID- 27556620 TI - Optical Feedback Control and Electrical-Optical Costimulation of Peripheral Nerves. AB - BACKGROUND: Optogenetics is an emerging technology that enables the expression of light-activated ion channels in mammalian cells. Neurons expressing light activated ion channels can be depolarized using the appropriate wavelength of light. Optical stimulation of neurons could have important implications for further understanding and managing peripheral nerve deficits leading to paresis or paralysis. This study examines the utility of this technology in a feedback controlled system and the advantages of coupling this technology with conventional electrical stimulation. METHODS: The sciatic nerves of transgenic mice expressing blue light-activated ion channels (channelrhodopsin-2) were optically manipulated to generate electromyographic responses in the gastrocnemius muscle and to develop two potential applications of this technology: feedback-controlled optical stimulation using a proportional-integral controller, and simultaneous electrical-optical stimulation. RESULTS: The authors observed repeatable and predictable behavior of the optical controller in over 200 trials and a statistically significant decreased error when using optical feedback control as opposed to non-feedback controlled stimulation (n = 6 limbs). A second application of this technology was the amplification of electrically generated peripheral nerve signals using an optical source. Amplification of electrical activity was observed even when subthreshold electrical stimulation was used. CONCLUSIONS: Optical feedback control and optical amplification of subthreshold activity extend the versatility of optogenetics in peripheral nerve applications. Optical feedback control is a new application of an approach originally developed for functional electrical stimulation. Optical amplification of subthreshold electrical stimulation motivates future investigations into the optical amplification of endogenous subthreshold peripheral nerve activity (e.g., following spinal cord injury). PMID- 27556621 TI - A Porcine Orthotopic Forelimb Vascularized Composite Allotransplantation Model: Technical Considerations and Translational Implications. AB - BACKGROUND: The restoration of complex tissue deficits with vascularized composite allotransplantation is a paradigm shift in reconstructive surgery. Clinical adoption of vascularized composite allotransplantation is limited by the need for systemic immunosuppression, with associated morbidity and mortality. Small-animal models lack the biological fidelity and preclinical relevance to enable translation of immunologic insights to humans. Large-animal models have been described; however, limitations persist, including the inability of heterotopic models to evaluate functional nerve regeneration, and the sensitivity of primates to toxicity of immunosuppressive drugs. The authors' novel orthotopic porcine limb transplant model has broad applicability and translational relevance to both immunologic and functional outcomes after vascularized composite allotransplantation. METHODS: Recipients underwent amputation at a level corresponding to the mid forearm. Replantation or transplantation of grafts was performed by plate fixation of the radio-ulna, microsurgical repair of brachial artery and median nerve, and extensor and flexor tendon repairs. Viability of replants was monitored clinically and radiologically. Transplants were monitored for clinicopathologic signs of rejection. Animals mobilized freely postoperatively. RESULTS: Replantations remained viable until the endpoint of 14 days. Transplants developed Banff grade 4 acute rejection by postoperative day 7. Doppler sonography and angiography confirmed vascular patency. Serial biopsy specimens of skin and histopathology of replants at endpoint confirmed tissue viability and bone healing. CONCLUSIONS: An orthotopic load-bearing porcine forelimb vascularized composite allotransplantation model was successfully established. Technical, procedural, and logistic considerations were optimized to allow model use for immunologic, bone healing, functional nerve regeneration, and other translational studies. PMID- 27556622 TI - A Novel Three-Dimensional Platform to Investigate Neoangiogenesis, Transendothelial Migration, and Metastasis of MDAMB-231 Breast Cancer Cells. AB - BACKGROUND: A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation. METHODS: Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture-seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated. RESULTS: After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture-seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel "neovessel." In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively). CONCLUSION: The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena. PMID- 27556623 TI - Free Functioning Gracilis Muscle Transfer versus Intercostal Nerve Transfer to Musculocutaneous Nerve for Restoration of Elbow Flexion after Traumatic Adult Brachial Pan-Plexus Injury. AB - BACKGROUND: After complete five-level root brachial plexus injury, free functional muscle transfer and intercostal nerve transfer to the musculocutaneous nerve are two potential reconstructive options for elbow flexion. The aim of this study was to determine the outcomes of free functional muscle transfer versus intercostal nerve-to-musculocutaneous nerve transfers with respect to strength. METHODS: Sixty-two patients who underwent free functional muscle transfer reconstruction or intercostal nerve-to-musculocutaneous nerve transfer for elbow flexion following a pan-plexus injury were included. The two groups were compared with respect to postoperative elbow flexion strength according to the British Medical Research Council grading system; preoperative and postoperative Disabilities of the Arm, Shoulder, and Hand questionnaire scores. RESULTS: In the free functional muscle transfer group, 67.7 percent of patients achieved M3 or M4 elbow flexion. In the intercostal nerve-to-musculocutaneous nerve transfer group, 41.9 percent of patients achieved M3 or M4 elbow flexion. The difference was statistically significant (p < 0.05). Changes in Disabilities of the Arm, Shoulder, and Hand questionnaire scores were not statistically significant. Average time from injury to surgery was significantly different (p < 0.01) in both groups. The number of intercostal nerves used for the musculocutaneous nerve transfer did not correlate with better elbow flexion grade. CONCLUSIONS: Based on this study, gracilis free functional muscle transfer reconstruction achieves better elbow flexion strength than intercostal nerve-to-musculocutaneous nerve transfer for elbow flexion after pan-plexus injury. The role of gracilis free functional muscle transfer should be carefully considered in acute reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27556624 TI - Skin-Sparing Debridement for Necrotizing Fasciitis in Children. AB - BACKGROUND: Necrotizing fasciitis is a serious soft-tissue infection associated with sepsis and tissue destruction. Surgical management usually requires extensive debridement of necrotic fascia and overlying skin, with significant aesthetic and functional consequences. The authors review the outcome of all recent cases of necrotizing fasciitis treated with skin-sparing debridement at their institution. METHODS: The authors conducted a retrospective review of all of their cases of necrotizing fasciitis treated with skin-sparing debridement. Medical records were evaluated with a standard form gathering relevant demographic and clinical data. All cases were confirmed as necrotizing fasciitis histologically. RESULTS: Ten patients were admitted with a diagnosis of necrotizing fasciitis. The median age of the patients was 4.9 years (range, 1.7 to 15.1 years). The majority of initial lesions were caused by chickenpox, mostly on the trunk. Interval from admission to surgery was 6 hours (range, 1 to 27.5 hours), with a median hospital stay of 11 days (range, 5 to 43 days). Median fasciectomy was 2.5 percent (range, 1 to 15 percent) of total body surface area, with a median skin excision of 0.25 percent of total body surface area (range, 0.1 to 3 percent). All patients received intravenous amoxicillin/clavulanic acid plus clindamycin. Delayed direct closure was possible for all patients. Median follow-up was 17 months (range, 3 to 79 months). There was no death in this series. CONCLUSION: This surgical management restricts skin excision to the area of definite skin necrosis, limiting skin excision to one-tenth of excised fascia, with long-term favorable cosmetic and functional results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27556625 TI - The Deep Temporal Nerve Transfer: An Anatomical Feasibility Study and Implications for Upper Facial Reanimation. AB - BACKGROUND: Facial paralysis has a profound impact on the brow, and currently static procedures are the mainstay of treatment. The deep temporal branches of the trigeminal nerve, given their proximity to the brow, may serve as possible donor nerves for both potential innervation of a free muscle transfer in patients with prolonged facial palsy or nerve transfers in acute or subacute palsy. As such, the authors present the detailed surgical anatomy of the deep temporal nerve, assessing feasibility for both functional muscle and nerve transfers, including a proposed surgical technique. METHODS: Thirty cadaver hemifaces were dissected to establish deep temporal nerve anatomy and perform axonal analysis. RESULTS: Two (53 percent) or three (47 percent) divisions of the deep temporal nerve were noted, with the most consistent division being the middle division (30 of 30 specimens). This division was consistently found approximately 4.1 cm (range, 3.7 to 4.5 cm) anterior to the tragus at the level of the zygomatic arch. For each 1 cm cranial to the arch, the nerve courses approximately 1 mm posteriorly. The number of axons in the proposed temporal branch is 1469 as it emerges from behind the zygomatic arch, 889 at 1 cm, 682 at 2 cm, 534 at 3 cm, 355 at 4 cm, 377 at 5 cm, and 256 at 6 cm. CONCLUSION: Given its anatomical consistency, and expendability, the middle division of the deep temporal nerve is a viable donor nerve for dynamic upper facial reanimation with either nerve transfer or functional muscle transfer, depending on the length of facial palsy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 27556626 TI - Lengthening Temporalis Myoplasty: Virtual Animation-Assisted Technical Video. AB - Lengthening temporalis myoplasty is a well-established procedure for dynamic palliative reanimation of the lip in facial palsy sequelae. The particularity of this technique is that the entire temporal muscle is transferred from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. To date, no video describing the technique was available. This is the first video describing the entire procedure, from preoperative markings through postoperative rehabilitation. In the video presented herein, the authors craft virtual three-dimensional animations in addition to a live operation on a patient performed by Daniel Labbe, who first described this technique 20 years ago. PMID- 27556627 TI - Regional Oxygen Saturation Index: A Novel Criterion for Free Flap Assessment Using Tissue Oximetry. AB - BACKGROUND: Tissue oximetry is a useful tool for postoperative free flap monitoring. Reported criterion values have been accurate; however, there are various complicated author-dependent criteria, and sometimes it is too late for flap salvage. The authors offer a new, simple criterion for faster and accurate detection of perfusion problems. METHODS: Intraoperatively, perfusion areas of various free perforator flaps were assessed by both indocyanine green angiography and regional oxygen saturation. The elevated flap was categorized into the early stained area, the delayed-stained area, and the no-stained area by indocyanine green angiography. The regional oxygen saturation index (regional oxygen saturation on the flap on the control nondissected portion) of each area was calculated. Postoperative continuous flap monitoring was conducted, recording the value of the regional oxygen saturation index at the early-stained area. The blood glucose measurement index was also recorded periodically. RESULTS: In 60 cases of perforator-based free flaps, intraoperative indocyanine green areas were significantly correlated with the values of regional oxygen saturation index. The postoperative regional oxygen saturation index showed very stable values in various types of perforator flaps, provided that no vascular problem occurred, and it never went below 0.75. When vascular problems occurred, the regional oxygen saturation index dropped below 0.75 in all three cases before the blood glucose measurement index and the absolute value of regional oxygen saturation dropped below the criterion value. CONCLUSION: The regional oxygen saturation index may be a simple and fast criterion for detecting vascular problems following free flap reconstruction compared with existing criteria. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II. PMID- 27556628 TI - Current Uses of Botulinum Neurotoxins in Plastic Surgery. AB - LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Recognize the various types of botulinum toxins and their differences. 2. Identify current indications, both approved and off-label. 3. Inject botulinum toxin to counteract various natural aging processes, including facial descent and rhytides. SUMMARY: Botulinum neurotoxin is a naturally synthesized microbial protein that has been applied in the management of various disorders. In particular, its application within the realm of plastic surgery is addressed in this article. After evaluating the medical literature, the seven indications with the highest quality trials for the use of botulinum neurotoxin in plastic surgery were as follows: rhytides, facial dystonias, facial nerve palsy and aberrant regeneration, hand tremor, palmar hyperhidrosis, neuropathic pain, and upper limb spasticity. PMID- 27556629 TI - The Medical Mission and Modern Core Competency Training: A 10-Year Follow-Up of Resident Experiences in Global Plastic Surgery. AB - BACKGROUND: The emphasis on cultural competency for physicians and surgeons is increasingly important, as communication with both patients and other providers significantly affects individual and system-wide outcomes. International surgical training has been shown to improve leadership skills, cultural competency, and technical proficiency of participants in short-term follow-up. This study explores the long-term impact of international surgical mission experiences on developing participants' core competencies, professional outcomes, and commitment to global health. METHODS: All 208 plastic and reconstructive surgeons who completed the Operation Smile Regan/Stryker fellowship programs between 2006 and 2015 were surveyed electronically. RESULTS: One hundred sixty-five surveys were returned, for an overall response rate of 79.3 percent. The majority of participants reported that the fellowship positively impacted all six Accreditation Council for Graduate Medical Education core competencies. Most participants who were attending physicians at the time of the survey were practicing general plastic surgery, with 42 percent in an academic/teaching environment, 32 percent in assistant/associate professor positions, and 6 percent in either a program director or department chairman position. The majority currently volunteer on local or international missions, and all respondents would consider volunteering again. CONCLUSIONS: Carefully structured and rigorously proctored programs such as the Regan/Stryker Fellowship offer plastic surgery residents the opportunity to gain valuable professional and personal experiences that benefit them long after their service experience. Programs of this nature can not only effectively improve cultural competency of physicians, but also positively influence their attitudes toward leadership and direct that potential to meet the growing need for surgical care in low- and middle-income countries. PMID- 27556630 TI - Revenue Generation and Plastic Surgery Training Programs: 1-Year Evaluation of a Plastic Surgery Consultation Service. AB - BACKGROUND: In academic institutions, residents make substantial contributions to clinical productivity. However, billing cannot be generated unless there is direct attending physician supervision of these services. The purpose of this study was to quantify clinical services provided by residents at a large academic medical center. METHODS: The authors performed a review of all consultations to the plastic surgery service between January 1 and December 31, 2014. Documentation was reviewed and hypothetical billing for services was generated using American Medical Association Current Procedural Terminology and evaluation and management codes. RESULTS: A total of 2367 consultations were reviewed during the 1-year study period. Residents provided services under indirect supervision for the majority of consultations [n = 1940 (81.9 percent)]. If these services had been billed, evaluation and management would have resulted in 6970 physician work relative value units. More than half of the encounters (52.0 percent) involved at least one procedure, resulting in an additional 3316 work relative value units from 1339 Current Procedural Terminology codes. Using a conservative estimate (2014 Medicare reimbursement rates), charges from these services would total $368,496. CONCLUSIONS: The plastic surgery consultation service is a potential source of uncaptured revenue for training programs using indirect supervision of residents. Greater than 10,000 work relative value units could have been generated from resident clinical services, which is considerably more than the national average productivity of a full-time, academic plastic surgeon. Capturing a portion of this revenue stream could improve the fiscal balance of training programs and improve the cost-effective use of resident productivity. PMID- 27556631 TI - Reply: Surgical Timing and the Menstrual Cycle Affect Wound Healing in Young Breast Reduction Patients. PMID- 27556632 TI - Reply: Surgical Timing and the Menstrual Cycle Affect Wound Healing in Young Breast Reduction Patients. PMID- 27556633 TI - Reply: Surgical Timing and the Menstrual Cycle Affect Wound Healing in Young Breast Reduction Patients. PMID- 27556635 TI - Assessement of doses to members of the public arising from the use of ornamental rocks in residences. AB - The main pathways to human exposure associated with naturally occurring radionuclides in ornamental rocks are external irradiation and the inhalation of radon. Usually, external doses and risks are assessed by using generic approaches in which the specific properties and use of the material are not considered. Moreover, limited information on radon inhalation dose due to the use of rock is available. The radionuclide concentrations in 180 rock samples reached a wide range of values: for 228Ra from <2 to 530 Bq kg-1, for 226Ra between <5 and 600 Bq kg-1and for 40K varied between 190 and 2797 Bq kg-1. Considering the rock properties, mathematical models, a residential scenario and radionuclide concentrations in the rocks, 222Rn concentrations and inhalation and external doses were estimated to range from 0.1 to 13 Bq m-3, from 0.01 and 0.26 mSv yr-1 and from 0.01 and 0.61 mSv yr-1, respectively. The ventilation and the emanation rates are key parameters for the Rn dose, whereas the location of the receptor significantly affects the external dose. The overestimations of doses and risks by the generic approaches highlight the necessity of considering the properties and use of the materials for those estimations. PMID- 27556634 TI - Concordance of copy number loss and down-regulation of tumor suppressor genes: a pan-cancer study. AB - BACKGROUND: Tumor suppressor genes (TSGs) encode the guardian molecules to control cell growth. The genomic alteration of TSGs may cause tumorigenesis and promote cancer progression. So far, investigators have mainly studied the functional effects of somatic single nucleotide variants in TSGs. Copy number variation (CNV) is another important form of genetic variation, and is often involved in cancer biology and drug treatment, but studies of CNV in TSGs are less represented in literature. In addition, there is a lack of a combinatory analysis of gene expression and CNV in this important gene set. Such a study may provide more insights into the relationship between gene dosage and tumorigenesis. To meet this demand, we performed a systematic analysis of CNVs and gene expression in TSGs to provide a systematic view of CNV and gene expression change in TSGs in pan-cancer. RESULTS: We identified 1170 TSGs with copy number gain or loss in 5846 tumor samples. Among them, 207 TSGs tended to have copy number loss (CNL), from which fifteen CNL hotspot regions were identified. The functional enrichment analysis revealed that the 207 TSGs were enriched in cancer-related pathways such as P53 signaling pathway and the P53 interactome. We further performed integrative analyses of CNV with gene expression using the data from the matched tumor samples. We found 81 TSGs with concordant CNL events and decreased gene expression in the tumor samples we examined. Remarkably, seven TSGs displayed concordant CNL and gene down regulation in at least 50 tumor samples: MTAP (212 samples), PTEN (139), MCPH1 (85), FBXO25 (67), SMAD4 (64), TRIM35 (57), and RB1 (54). Specifically to MTAP, this concordance was found in 14 cancer types, an observation that is not much reported in literature yet. Further network-based analysis revealed that these TSGs with concordant CNL and gene down-regulation were highly connected. CONCLUSIONS: This study provides a draft landscape of CNV in pan-cancer. Our findings of systematic concordance between CNL and down-regulation of gene expression may help better understand the TSG biology in tumorigenesis and cancer progression. PMID- 27556636 TI - Benchmarking of de novo assembly algorithms for Nanopore data reveals optimal performance of OLC approaches. AB - BACKGROUND: Improved DNA sequencing methods have transformed the field of genomics over the last decade. This has become possible due to the development of inexpensive short read sequencing technologies which have now resulted in three generations of sequencing platforms. More recently, a new fourth generation of Nanopore based single molecule sequencing technology, was developed based on MinION((r)) sequencer which is portable, inexpensive and fast. It is capable of generating reads of length greater than 100 kb. Though it has many specific advantages, the two major limitations of the MinION reads are high error rates and the need for the development of downstream pipelines. The algorithms for error correction have already emerged, while development of pipelines is still at nascent stage. RESULTS: In this study, we benchmarked available assembler algorithms to find an appropriate framework that can efficiently assemble Nanopore sequenced reads. To address this, we employed genome-scale Nanopore sequenced datasets available for E. coli and yeast genomes respectively. In order to comprehensively evaluate multiple algorithmic frameworks, we included assemblers based on de Bruijn graphs (Velvet and ABySS), Overlap Layout Consensus (OLC) (Celera) and Greedy extension (SSAKE) approaches. We analyzed the quality, accuracy of the assemblies as well as the computational performance of each of the assemblers included in our benchmark. Our analysis unveiled that OLC-based algorithm, Celera, could generate a high quality assembly with ten times higher N50 & mean contig values as well as one-fifth the number of total number of contigs compared to other tools. Celera was also found to exhibit an average genome coverage of 12 % in E. coli dataset and 70 % in Yeast dataset as well as relatively lesser run times. In contrast, de Bruijn graph based assemblers Velvet and ABySS generated the assemblies of moderate quality, in less time when there is no limitation on the memory allocation, while greedy extension based algorithm SSAKE generated an assembly of very poor quality but with genome coverage of 90 % on yeast dataset. CONCLUSION: OLC can be considered as a favorable algorithmic framework for the development of assembler tools for Nanopore-based data, followed by de Bruijn based algorithms as they consume relatively less or similar run times as OLC-based algorithms for generating assembly, irrespective of the memory allocated for the task. However, few improvements must be made to the existing de Bruijn implementations in order to generate an assembly with reasonable quality. Our findings should help in stimulating the development of novel assemblers for handling Nanopore sequence data. PMID- 27556637 TI - EpiTracer - an algorithm for identifying epicenters in condition-specific biological networks. AB - BACKGROUND: In biological systems, diseases are caused by small perturbations in a complex network of interactions between proteins. Perturbations typically affect only a small number of proteins, which go on to disturb a larger part of the network. To counteract this, a stress-response is launched, resulting in a complex pattern of variations in the cell. Identifying the key players involved in either spreading the perturbation or responding to it can give us important insights. RESULTS: We develop an algorithm, EpiTracer, which identifies the key proteins, or epicenters, from which a large number of changes in the protein protein interaction (PPI) network ripple out. We propose a new centrality measure, ripple centrality, which measures how effectively a change at a particular node can ripple across the network by identifying highest activity paths specific to the condition of interest, obtained by mapping gene expression profiles to the PPI network. We demonstrate the algorithm using an overexpression study and a knockdown study. In the overexpression study, the gene that was overexpressed (PARK2) was highlighted as the most important epicenter specific to the perturbation. The other top-ranked epicenters were involved in either supporting the activity of PARK2, or counteracting it. Also, 5 of the identified epicenters showed no significant differential expression, showing that our method can find information which simple differential expression analysis cannot. In the second dataset (SP1 knockdown), alternative regulators of SP1 targets were highlighted as epicenters. Also, the gene that was knocked down (SP1) was picked up as an epicenter specific to the control condition. Sensitivity analysis showed that the genes identified as epicenters remain largely unaffected by small changes. CONCLUSIONS: We develop an algorithm, EpiTracer, to find epicenters in condition-specific biological networks, given the PPI network and gene expression levels. EpiTracer includes programs which can extract the immediate influence zone of epicenters and provide a summary of dysregulated genes, facilitating quick biological analysis. We demonstrate its efficacy on two datasets with differing characteristics, highlighting its general applicability. We also show that EpiTracer is not sensitive to minor changes in the network. The source code for EpiTracer is provided at Github ( https://github.com/narmada26/EpiTracer ). PMID- 27556638 TI - New Methods for the Site-Selective Placement of Peptides on a Microelectrode Array: Probing VEGF-v107 Binding as Proof of Concept. AB - Cu(I)-catalyzed "click" reactions cannot be performed on a borate ester derived polymer coating on a microelectrode array because the Cu(II) precursor for the catalyst triggers background reactions between both acetylene and azide groups with the polymer surface. Fortunately, the Cu(II)-background reaction can itself be used to site-selectively add the acetylene and azide nucleophiles to the surface of the array. In this way, molecules previously functionalized for use in "click" reactions can be added directly to the array. In a similar fashion, activated esters can be added site-selectively to a borate ester coated array. The new chemistry can be used to explore new biological interactions on the arrays. Specifically, the binding of a v107 derived peptide with both human and murine VEGF was probed using a functionalized microelectrode array. PMID- 27556639 TI - Efficacy of stereotactic radiotherapy for brain metastases using dynamic jaws technology in the helical tomotherapy system. AB - OBJECTIVE: Dynamic jaws (DJ) are expected to be useful in stereotactic radiotherapy (SRT) for brain metastases (BM). The efficacy and optimal dose fractionation were investigated. METHODS: In a planning study, 63 treatment plans were generated for the following 3 conditions: 1.0-cm fixed jaws (FJ), 2.5-cm FJ and 2.5-cm DJ. In a clinical study, 30 Gy/3 fr, 35 Gy/5 fr or 37.5 Gy/5 fr were prescribed depending on tumour size. Clinical results of groups treated with 2.5 cm DJ plans and 1.0-cm FJ were compared. RESULTS: In the planning study, the treatment times in 2.5-cm DJ and FJ plans were less than that in 1.0-cm FJ plans (p < 0.001). The brain doses in 1.0-cm FJ plans and 2.5-cm DJ plans were smaller than those in 2.5-cm FJ plans (p < 0.05). In the clinical study, 34 patients with 68 BM were treated with SRT. Of those, 15 patients with 34 BM were treated with 2.5-cm DJ plans and 19 patients with 34 BM were treated with 1.0-cm FJ plans. The overall survival and local tumour control (LC) rates were 52 and 93% at 12 months, respectively. The DJ system achieved favourable LC and 29% shorter treatment time compared with the FJ system (p < 0.001). Grade 2 or 3 necrosis occurred more frequently in patients with 15 cc or larger tumour volumes (p = 0.05). CONCLUSION: DJ technology enables treatment time to be reduced without worsening the dose distribution and clinical efficacy. The prescribed doses in this study may be acceptable for patients with small tumour volumes. ADVANCES IN KNOWLEDGE: DJ technology enables treatment time to be reduced without worsening the dose. PMID- 27556640 TI - Optical Gain in MoS2 via Coupling with Nanostructured Substrate: Fabry-Perot Interference and Plasmonic Excitation. AB - Despite the direct band gap of monolayer transition metal dichalcogenides (TMDs), their optical gain remains limited because of the poor light absorption in atomically thin, layered materials. Most approaches to improve the optical gain of TMDs mainly involve modulation of the active materials or multilayer stacking. Here, we report a method to enhance the optical absorption and emission in MoS2 simply through the design of a nanostructured substrate. The substrate consisted of a dielectric nanofilm spacer (TiO2) and metal film. The overall photoluminescence intensity from monolayer MoS2 on the nanostructured substrate was engineered based on the TiO2 thickness and amplified by Fabry-Perot interference. In addition, the neutral exciton emission was selectively amplified by plasmonic excitations from the local field originating from the surface roughness of the metal film with spacer thicknesses of less than 10 nm. We further demonstrate that the quality factor of the device can also be engineered by selecting a spacer material with a different refractive index. PMID- 27556641 TI - Intradiploic Epidermoid Tumors of the Cranium: Case Report with Review of the Literature. AB - Introduction Epidermoid cysts are a rare intracranial tumor, mostly arising from the cerebellar pontine angle but sporadically arising from the cranial diploe. Intradiploic epidermoids were first described in 1838 and have since been reported in sporadic case reports and case series. Due to the scarcity of cases, no institution has a large enough case series to fully characterize this tumor. We review numerous case series to better describe intradiploic epidermoids. Methods Using a search for intradiploic epidermoid, several case reports and series were found. References from these articles were reviewed for further cases. Results A total of 169 cases of intradiploic epidermoids were reviewed. The average age of patients presenting with intradiploic epidermoids was 38.1 years (standard error of the mean: 1.56). Overall, 68.9% of these patients presented with localized swelling over the scalp, 32.3% with headaches, and 42.7% with other neurologic symptoms. The most common location of the tumor was the frontal bones, with the least common the sphenoid, zygomatic, and maxillary bone. Surgical resection was curative in most cases, with a 3.2% mortality. Recurrence rate was only 5.8%, with nearly all occurring before 1999. Of the recurrent cases, malignant transformation to squamous cell carcinoma was estimated at 44% (4/9). Most of these cases are thought to have occurred as a result of incomplete resection of a primary intradiploic epidermoid. Conclusions To date, this is the largest review of intradiploic epidermoids reported in the literature. In the reported cases, most had a benign course. However, there are occasional malignant transformations, and some patients have neurologic sequelae from mass effect or tumor infiltration. This is a surgically curative tumor in most cases. PMID- 27556642 TI - The Geometric Phase of Stock Trading. AB - Geometric phases describe how in a continuous-time dynamical system the displacement of a variable (called phase variable) can be related to other variables (shape variables) undergoing a cyclic motion, according to an area rule. The aim of this paper is to show that geometric phases can exist also for discrete-time systems, and even when the cycles in shape space have zero area. A context in which this principle can be applied is stock trading. A zero-area cycle in shape space represents the type of trading operations normally carried out by high-frequency traders (entering and exiting a position on a fast time scale), while the phase variable represents the cash balance of a trader. Under the assumption that trading impacts stock prices, even zero-area cyclic trading operations can induce geometric phases, i.e., profits or losses, without affecting the stock quote. PMID- 27556643 TI - Affective Beliefs Influence the Experience of Eating Meat. AB - People believe they experience the world objectively, but research continually demonstrates that beliefs influence perception. Emerging research indicates that beliefs influence the experience of eating. In three studies, we test whether beliefs about how animals are raised can influence the experience of eating meat. Samples of meat were paired with descriptions of animals raised on factory farms or raised on humane farms. Importantly, the meat samples in both conditions were identical. However, participants experienced the samples differently: meat paired with factory farm descriptions looked, smelled, and tasted less pleasant. Even basic properties of flavor were influenced: factory farmed samples tasted more salty and greasy. Finally, actual behavior was influenced: participants consumed less when samples were paired with factory farm descriptions. These findings demonstrate that the experience of eating is not determined solely by physical properties of stimuli-beliefs also shape experience. PMID- 27556644 TI - Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements. AB - BACKGROUND: There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. CONCLUSIONS/SIGNIFICANCE: The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification. PMID- 27556646 TI - Social Groups Prioritize Selective Attention to Faces: How Social Identity Shapes Distractor Interference. AB - Human faces automatically attract visual attention and this process appears to be guided by social group memberships. In two experiments, we examined how social groups guide selective attention toward in-group and out-group faces. Black and White participants detected a target letter among letter strings superimposed on faces (Experiment 1). White participants were less accurate on trials with racial out-group (Black) compared to in-group (White) distractor faces. Likewise, Black participants were less accurate on trials with racial out-group (White) compared to in-group (Black) distractor faces. However, this pattern of out-group bias was only evident under high perceptual load-when the task was visually difficult. To examine the malleability of this pattern of racial bias, a separate sample of participants were assigned to mixed-race minimal groups (Experiment 2). Participants assigned to groups were less accurate on trials with their minimal in-group members compared to minimal out-group distractor faces, regardless of race. Again, this pattern of out-group bias was only evident under high perceptual load. Taken together, these results suggest that social identity guides selective attention toward motivationally relevant social groups-shifting from out-group bias in the domain of race to in-group bias in the domain of minimal groups-when perceptual resources are scarce. PMID- 27556647 TI - The Nurse Leader Role in Crisis Management. AB - Leaders from the American Organization of Nurse Executives describe the dynamic state of today's healthcare system related to crisis management. Adaptive leadership, driven by strong values and morality, can guide leaders and organizations through the most difficult times. PMID- 27556648 TI - The Commission on Magnet(r) Recognition. AB - The American Nurses Credentialing Center (ANCC) Commission on Magnet(r) Recognition is a voluntary governing body that oversees the Magnet Recognition Program(r). Commission members are appointed by the ANCC Board of Directors and are expert representatives from various sectors of the nursing community. In addition, 1 commission member represents public consumers. PMID- 27556649 TI - Knowledge Discovery and Data Mining: Implications for Nurse Leaders. AB - As systems evolve, their tendency is to become more complex. Studies in the field of complex systems have generated new perspectives on the application of management strategies in health systems. This is the 2nd in a series of articles addressing the mounting challenges faced by nursing leaders demanding insights from the vast amounts of information collected and stored by their organizations. PMID- 27556645 TI - Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma. AB - BACKGROUND: Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. AIMS: To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. METHODS: PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. RESULTS: PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet-derived microparticles, platelets, and platelet aggregates whereas SMHEF pulses primarily resulted in platelet-derived microparticles. Microparticles and platelets in PRP activated with SMLEF bipolar pulses had significantly lower annexin V-positivity than those following SMHEF activation. In contrast, the % P-selectin positivity and surface P-selectin expression (MFI) for platelets and microparticles in SMLEF bipolar pulse activated PRP was significantly higher than that in SMHEF-activated PRP, but not significantly different from that produced by thrombin activation. Higher levels of EGF were observed following either SMLEF bipolar pulses or SMHEF pulses of PRP than after bovine thrombin activation while VEGF, PDGF, and PF4 levels were similar with all three activating conditions. Cell proliferation was significantly increased by releasates of both SMLEF bipolar pulse and SMHEF pulse activated PRP compared to plasma alone. CONCLUSIONS: PEF activation of PRP at bipolar low vs. monopolar high field strength results in differential platelet derived microparticle production and activation of platelet surface procoagulant markers while inducing similar release of growth factors and similar capacity to induce cell proliferation. Stimulation of PRP with SMLEF bipolar pulses is gentler than SMHEF pulses, resulting in less platelet microparticle generation but with overall activation levels similar to that obtained with thrombin. These results suggest that PEF provides the means to alter, in a controlled fashion, PRP properties thereby enabling evaluation of their effects on wound healing and clinical outcomes. PMID- 27556650 TI - Engaging Nurses in the Development and Implementation of a Professional Practice Model Through Nursing Salons. AB - Developing creative ways to solicit nurse input into practice is a challenge for nurse executives. Engaging nurses through the use of nursing salons was seen as an innovative way to engage nurses. Feedback from nurses participating in salons informed development of a Professional Practice Model that reflects nursing practice at this large academic medical center and provided a voice to nursing. PMID- 27556651 TI - Is Spending More Time Associated With Less Missed Care?: A Comparison of Time Use and Missed Care Across 15 Nursing Units at 2 Hospitals. AB - OBJECTIVE: The aim of this study is to examine the relationship between nursing time use and perceptions of missed care. BACKGROUND: Recent literature has highlighted the problem of missed nursing care, but little is known about how nurses' time use patterns are associated with reports of missed care. METHODS: In 15 nursing units at 2 hospitals, we assessed registered nurse (RN) perceptions of missed care, observed time use by RNs, and examined the relationship between time spent and degree of missed care at the nursing unit level. RESULTS: Patterns of time use were similar across hospitals, with 25% of time spent on documentation. For 6 different categories of nursing tasks, no association was detected between time use, including time spent on documentation, and the degree of missed care at the nursing unit level. CONCLUSIONS: Nursing time use cannot fully explain variation in missed care across nursing units. Further work is needed to account for patterns of missed care. PMID- 27556652 TI - Understanding Mentorship in a Research Training Program for Point-of-Care Clinicians. AB - Evidence-based practice (EBP) is essential to high-quality patient care and can contribute to healthcare cost savings, yet nurses and other clinicians at the point of care report barriers to engagement with research and translating it to the clinical setting. Mentorship has been shown to improve nurses' understanding and implementation of EBP. In this article, we describe a mentorship model in a successful program to support point-of-care nurses in conducting small-scale research projects, many of which have led to practice changes and/or cost savings. PMID- 27556653 TI - What Nurses Do During Time Scarcity-and Why. AB - Time scarcity is a common occurrence in the nurse work environment that stimulates a decision-making process, known as clinical prioritization or implicit rationing. In implicit rationing, nurses must decide what care they will complete and what they will leave unfinished. Five mechanisms that influence this process are supported in the literature. The effects of these influential mechanisms leave patients vulnerable to unmet educational, psychological, care coordination and discharge planning needs. Potential areas for intervention by nurse leaders include redesigning care delivery models to reduce time scarcity, adding balancing measures to performance monitoring systems to promote patient centered care, and creating work cultures that support the values of nursing. PMID- 27556654 TI - A Metasynthesis Exploring Nurses and Women on Governing Boards. AB - OBJECTIVE: The purpose of this article is to present the results of a metasynthesis addressing significant issues relating to board appointments for nurses and women. BACKGROUND: Nurses are rarely engaged as voting board members even though they are positioned to add value. When nurses and women are appointed to boards, their experiences reflect the struggles associated with traditional patriarchal board norms. METHOD: A metasynthesis of qualitative studies was conducted. Seven studies from nursing and business literature were analyzed using the meta-ethnography methodology. RESULTS: Proving worth is the central issue of nurses and women on boards. CONCLUSION: Boardroom parity for nurses and women is an important social agenda with implications for strategic decision making in healthcare and business. PMID- 27556655 TI - Describing Nurse Leaders' and Direct Care Nurses' Perceptions of a Healthy Work Environment in Acute Care Settings, Part 2. AB - BACKGROUND: The American Association of Critical-Care Nurses (AACN) Healthy Work Environment Assessment Tool was developed as a simple screening tool to assess the characteristics of a healthy work environment (HWE) in critical care environments. PURPOSES: The purposes of these 2 qualitative research studies are to explore the nurse leaders' and direct care nurses' perceptions of the meaning of a HWE, to describe the nurse leaders' and direct care nurses' perceptions of a HWE, and to define the characteristics of a HWE in acute care settings. METHODS: Exploratory descriptive designs using focus groups and guided questions with tape recorded interviews were used to define the characteristics of an HWE. RESULTS: The 6 original themes from AACN HWE standards and 2 new themes emerged as a result of the nurse leaders and direct care nurses defining the characteristics of a HWE, which included appropriate staffing, authentic leadership, effective decision making, meaningful recognition, skilled communication, true collaboration genuine teamwork, and physical and psychological safety. The qualitative statements from these 2 studies will be used in future studies to describe and develop HWE scales for nurse leaders and direct care nurses and to assess the psychometric properties of these new tools. PMID- 27556656 TI - Noise Exposure on Pediatric Inpatient Units. AB - BACKGROUND: Noise is a problem placing registered nurses (RNs) at risk for safety events, decreased job performance, fatigue, irritability, and hearing loss. OBJECTIVE: The purpose of this study is to measure noise levels and sources on pediatric inpatient units as well as to explore the health impact of noise on RNs. METHODS: This was a descriptive nonexperimental study with 65 pediatric RNs from 14 units. Noise (levels, source, location, and activity), heart rate (HR), and stress were measured. Correlations between sound pressure levels (SPLs), HR, and stress were examined. RESULTS: Mean (SD) SPLs were 75.8 (8.9) dBA and were significantly higher than SPLs for patients. Noise was significantly associated with HR but not with time in tachycardia or stress. Primary sources of noise were employee conversations in patient rooms. CONCLUSIONS: On all units, SPLs exceeded protection agency guidelines. Cost-prohibitive structural changes underscore the importance of using behavioral and culture modification to reduce noise. PMID- 27556657 TI - Nurses' Perception of Shared Decision-Making Processes: Quantifying a Shared Governance Culture. AB - OBJECTIVE: The aim of this study is to describe how measuring the perceived and desired decision-making capacity of nurses in a model of shared governance (SG) can be beneficial. BACKGROUND: Shared governance (SG) increases nurse's control over professional practice. Engagement in SG can be impacted by how much decision making power nurses desire. This concept related to decision making has been termed decisional involvement (DI). Few studies exist that examine the concept of DI. METHODS: Using the Decisional Involvement Scale, acute care nurses were sampled concerning desired and perceived decision making on 21 topics related to nursing practice. RESULTS: Analysis of the data identified different governance priorities for several areas. Of particular interest was that those nurses on SG councils for more than 5 years did not report higher satisfaction with decision involvement. CONCLUSIONS: A comprehensive evaluation of shared decision making was a valuable tool to establish a baseline of data and seek opportunities for improvement. A well-integrated model of SG requires continuous improvement and analysis to be sustained. Measuring and evaluating staff nurses desire to control varied aspects of DI can allow organizations to make focused efforts to strengthen SG. PMID- 27556658 TI - Maximizing Cures and Preserving Function in Head and Neck Cancers. PMID- 27556659 TI - Management of Oropharyngeal Cancer in the HPV Era. AB - BACKGROUND: Historically, oropharyngeal cancer (OPC) has been attributed to risk factors such as smoking and alcohol use. The increased incidence of OPC has been driven by human papillomavirus (HPV) infection. METHODS: A search of the literature involving HPV infection and OPC was performed, along with a search of ongoing clinical trials regarding HPV-positive OPC. RESULTS: This review summarizes the differences in epidemiology and prognosis of HPV-positive OPC compared with non-HPV-related OPC. It will also discuss use of de-escalating treatment to minimize toxicity while maintaining excellent outcomes. Disease management is also addressed, including prevention and follow-up recommendations for this cohort of patients. CONCLUSIONS: HPV-positive OPC is a distinct disease, and efforts should be made to personalize its management. Preventive measures and vaccinations, along with de-escalation of treatment, may help optimize outcomes in this population. PMID- 27556660 TI - Definitive Radiotherapy for Squamous Cell Carcinoma of the Glottic Larynx. AB - BACKGROUND: Depending on the extent of disease, squamous cell carcinoma (SCC) of the glottis is managed with surgery, radiotherapy (RT), or a combination of these modalities. Patients with advanced disease may receive concomitant chemotherapy in conjunction with definitive or postoperative RT. METHODS: The treatment policies of the University of Florida and patient outcomes are reviewed. RESULTS: The likelihood of cure after RT for carcinoma in situ (Tis) to T2 glottic SCC varies from 70% to 94% depending on tumor stage. Consideration should be given to adding weekly cisplatin for patients with T2b SCC because of the high local recurrence rate after RT alone. The probability of cure is about 65% to 80% for select low-volume (<= 3.5 cc) T3 to T4 glottic SCC after RT. These patients should be considered for concomitant weekly cisplatin. Higher-volume tumors, particularly those with airway compromise, should be treated with laryngectomy and postoperative RT. CONCLUSION: Definitive RT is an excellent treatment for select patients with laryngeal cancer. PMID- 27556661 TI - Clinical Benefits of Proton Beam Therapy for Tumors of the Skull Base. AB - BACKGROUND: The unique radiobiological properties of protons have been understood for many years. In addition, many of the clinical benefits of radiotherapy were first noted in tumors involving the skull base. More public attention has been given to proton beam therapy due to the increasing number of centers now in operation or in the planning stages for offering this treatment option. METHODS: We reviewed the physical properties of protons and the clinical studies performed to justify their use in the management of skull-base tumors and determine the benefits of proton beam therapy. RESULTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas. CONCLUSIONS: Use of proton beam therapy may be beneficial in select patients. Surgical and medical oncologists should have a general understanding of such cases to facilitate their appropriate referral. PMID- 27556662 TI - Management of BCC and SCC of the Head and Neck. AB - BACKGROUND: For decades radiotherapy (RT) has been shown to treat skin cancers; however, the indications, delivery methods, and techniques for RT continue to evolve. METHODS: Relevant prospective and retrospective reports were reviewed that addressed outcomes with, indications for, and delivery techniques used with RT for the management of cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the head and neck. RESULTS: Rates of local control higher than 90% are typically achievable for early-stage BCC and SCC of the head and neck. RT is often recommended for tumors located in cosmetically or functionally sensitive areas of the face, for patients who cannot tolerate anesthesia, for those taking anticoagulants, or for patients who prefer RT to other treatment options. A wide range of radiation doses, daily fractionation schedules, and radiation techniques have been shown to be effective for management. In general, postoperative local radiation is recommended following excision for patients with high-risk factors, including those whose tumors have close or positive margins, perineural invasion, invasion of the bone or nerves, or those with recurrent disease. CONCLUSIONS: RT plays an integral role in the treatment of primary and postoperative cutaneous BCC and SCC of the head and neck. Prospective trials are in progress to address the roles of concurrent systemic therapy and RT for both cutaneous BCC and SCC. PMID- 27556663 TI - Treatment of Head and Neck Paragangliomas. AB - BACKGROUND: Commonly occurring in the head and neck, paragangliomas are typically benign, highly vascular neoplasms embryologically originating from the extra adrenal paraganglia of the neural crest. Frequently, these tumors are associated with the vagus or tympanic plexus nerve or the carotid artery, or jugular bulb. Their clinical presentation can vary across a wide spectrum of signs and symptoms. METHODS: We reviewed and compared standard treatment approaches for paragangliomas of the head and neck. RESULTS: In general, surgery is the first line choice of therapy for carotid body tumors, whereas radiotherapy is the first line option for jugular and vagal paragangliomas. CONCLUSIONS: Because of the complexity of clinical scenarios and treatment options for paragangliomas, a multidisciplinary algorithmic approach should be used for treating paragangliomas. The approach should emphasize single-modality treatment that yields excellent rates of tumor control, low rates of severe, iatrogenic morbidity, and the preservation of long-term function in this patient population. PMID- 27556664 TI - Multidisciplinary Management of Salivary Gland Cancers. AB - BACKGROUND: Salivary carcinomas are a rare group of biologically diverse neoplasms affecting the head and neck. The wide array of different histological entities and clinical presentations has historically limited attempts to establish well-defined treatment algorithms. In general, low-risk lesions can be managed with a single treatment modality, whereas advanced lesions require a more complex, multidisciplinary approach. METHODS: The relevant literature was reviewed, focusing on diagnostic and treatment algorithms for salivary malignancies. RESULTS: Salivary carcinomas with high-risk features require an aggressive treatment approach with complete surgical resection, neck dissection to appropriate cervical lymph-node basins, and postoperative radiotherapy. CONCLUSIONS: The heterogeneity of salivary neoplasms represents a unique clinical challenge. Despite the multidisciplinary management paradigm detailed in this review, outcomes for advanced disease are unsatisfactory. Future progress will likely require the addition of novel systemic therapeutic strategies. PMID- 27556665 TI - Practical Issues for Retroperitoneal Sarcoma. AB - BACKGROUND: Retroperitoneal sarcoma is rare. Using initial specimens on biopsy, a definitive diagnosis of histological subtypes is ideal but not always achievable. METHODS: A retrospective institutional review was performed for all cases of adult retroperitoneal sarcoma from 1996 to 2015. A review of the literature was also performed related to the distribution of retroperitoneal sarcoma subtypes. A meta-analysis was performed. RESULTS: Liposarcoma is the most common subtype (45%), followed by leiomyosarcoma (21%), not otherwise specified (8%), and undifferentiated pleomorphic sarcoma (6%) by literature review. Data from Moffitt Cancer Center demonstrate the same general distribution for subtypes of retroperitoneal sarcoma. A pathology-based algorithm for the diagnosis of retroperitoneal sarcoma is illustrated, and common pitfalls in the pathology of retroperitoneal sarcoma are discussed. CONCLUSIONS: An informative diagnosis of retroperitoneal sarcoma via specimens on biopsy is achievable and meaningful to guide effective therapy. A practical and multidisciplinary algorithm focused on the histopathology is helpful for the management of retroperitoneal sarcoma. PMID- 27556666 TI - Primary Gangrenous Cutaneous Mold Infections in a Patient With Cancer and Neutropenia. AB - BACKGROUND: Opportunistic fungal infections caused by Aspergillus and Candida followed by infections with Fusarium, Rhizopus, Mucor, and Alternaria species are an important cause of morbidity and mortality in patients with hematological malignancies. Cutaneous mucormycosis infections are rare, and the incidence, outcomes, and factors associated with survival in the setting of hematological malignancies are not clear. METHODS: A literature search was conducted for all cases of primary cutaneous mold infections in patients with hematological malignancy, of which 50 cases were found. Our case of a patient with a hematological malignancy who sustained a cat bite that in turn caused a primary cutaneous mold infection is also included. RESULTS: In the 51 cases identified, 66.7% were neutropenic upon presentation, and 54.9% were male with an average age of 32 years. Aspergillus species (33.3%) was the most cited followed by Rhizopus species (19.6%). Overall mortality rate was 29.4% and was observed more frequently in patients with neutropenia (60.0%) and without surgical intervention (73.3%). Survival rate was higher (35.3%) for cases utilizing both antifungal and surgical intervention. The antifungal agent with the highest survival rate was amphotericin B and its formulations (58.8%). CONCLUSIONS: Neutropenia within hematological malignancies demonstrate a risk for developing severe cutaneous fungal infections, of which primary cutaneous mucormycosis can carry significant mortality. Combination antifungal therapy and surgical debridement appears to be associated with higher survival outcomes and warrants further investigation. PMID- 27556667 TI - Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia. AB - Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed. PMID- 27556668 TI - Marijuana Smoking in Patients With Leukemia. AB - Worldwide, marijuana (cannabis) is a widely used drug. The incidence of marijuana smoking is increasing and is second only to tobacco as the most widely smoked substance in the general population. It is also the second most commonly used recreational drug after alcohol. Some adverse effects of marijuana smoking have been documented; however, the number of studies on the pulmonary effects of marijuana in individuals with leukemia is limited. In our case series, we report on 2 men with acute myeloid leukemia with miliary nodular lung patterns on computed tomography of the chest due to heavy marijuana use. We also report on 2 patients with acute lymphocytic leukemia who had a history of smoking marijuana and then developed lung opacities consistent with mold infection. PMID- 27556669 TI - Platelet-to-Lymphocyte Ratio and Use of NSAIDs During the Perioperative Period as Prognostic Indicators in Patients With NSCLC Undergoing Surgery. AB - BACKGROUND: Hematological biomarkers of inflammation such as the neutrophil-to lymphocytic rate have been reported as predictors of survival in a variety of cancers. The aim of the present study was to investigate the prognostic value of the perioperative platelet-to-lymphocyte ratio in patients with non-small-cell lung cancer (NSCLC) and to elucidate the effects of the perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) on tumor recurrence and survival in patients undergoing surgical resection for NSCLC. METHODS: This retrospective study included data from 1,637 patients who underwent surgical resection for stage I, II, or III NSCLC. Perioperative data and tumor-related variables were included. Univariate and multivariable Cox proportional hazard ratio (HR) models were used to evaluate the association between perioperative platelet-to lymphocyte ratio and NSAID use on recurrence-free survival (RFS) and overall survival (OS). RESULTS: Multivariate analysis showed that a preoperative platelet to-lymphocyte ratio of at least 180 was associated with reduced rates of RFS (HR = 1.22; 95% confidence interval [CI], 1.03-1.45; P = .019) and OS (HR = 1.33; 95% CI, 1.10-1.62; P = .004). Perioperative use of NSAIDs showed no statistically significant changes in RFS and OS rates (P = .72 and P = .44, respectively). CONCLUSIONS: A higher preoperative inflammatory status is associated with decreased rates of RFS and OS in patients with NSCLC undergoing curative surgery. Perioperative use of NSAIDs was not found to be an independent predictor of survival. PMID- 27556670 TI - Resection of the First Rib With Preservation of the T1 Nerve Root in Pancoast Tumors of the Lung. AB - BACKGROUND: Surgical outcomes for Pancoast (superior sulcus) tumors of the lung have significantly changed during the last few decades and have improved with use of curative-intent surgery by utilizing en bloc complete resections. METHODS: A retrospective analysis was conducted of 11 selected patients treated at Moffitt Cancer Center from 2007 to 2016. Data from patient records were collected and analyzed. RESULTS: All 11 patients with a Pancoast tumor involving the first rib had their T1 root preserved at surgery. In 10 patients (90.9%), the tumor was removed en bloc. Clear margins of resection were documented in 4 cases (36.0%). No patient developed postoperative hand weakness, but 3 patients (27.3%) had minor postoperative complications, including air leak, chylothorax, and pericardial effusion. One iatrogenic injury to the subclavian artery was reported during surgery; the injury was subsequently repaired. No operative mortality was reported. CONCLUSIONS: Radical resection of Pancoast tumors is considered to be safe, and preserving the T1 nerve root provides more favorable, functional outcomes. PMID- 27556671 TI - Feasibility, Preliminary Efficacy, and Lessons Learned From a Garden-Based Lifestyle Intervention for Cancer Survivors. AB - BACKGROUND: Cancer survivors remain at increased risk for secondary malignancies, comorbidities, and all-cause mortality. Lifestyle behaviors, such as diet and physical activity, are strongly linked to a decreased risk of chronic disease and improved health outcomes, yet a paucity of research has been conducted in this vulnerable population. METHODS: Adult cancer survivors were recruited to participate in Growing Hope, an experimental single-group study designed to assess the feasibility and efficacy of a theory-driven and evidence-based intervention. For 4 months, 22 participants received group and individual education and had access to harvesting fresh produce at an urban garden. Data on program satisfaction, compliance, diet, and physical activity were collected via surveys; anthropometrics, blood values, and skin carotenoids were objectively measured. RESULTS: The intervention resulted in significant improvements in consumption of fruits and vegetables (P = .003), decreased consumption of red and processed meats (P = .030) and sugar-sweetened beverages (P = .020). Levels of skin carotenoids, fasting blood glucose, and non-high density lipoprotein cholesterol were also significantly improved (P = .011, P = .043, and P = .05, respectively). CONCLUSIONS: The results of this study support the feasibility and efficacy of a multifaceted, garden-based intervention for cancer survivors. In addition, these preliminary results demonstrate a positive impact aligning with the current lifestyle recommendations for cancer survivorship. Larger randomized controlled trials are warranted to define impact on sustained health outcomes. PMID- 27556672 TI - Hypofractionated Stereotactic Radiotherapy for Auditory Canal or Middle Ear Cancer. AB - BACKGROUND: Stereotactic radiotherapy (SRT) may represent a new treatment option for individuals with auditory canal or middle ear cancer. METHODS: Study participants with pathologically proven ear cancer were treated with SRT (35 Gy for 3 fractions or 40 Gy for 5 fractions) as first-line therapy. When local tumor recurrence developed following SRT, subtotal temporal bone resection and postoperative chemoradiotherapy were performed as salvage treatment. Boluses were used for the initial 14 study patients. RESULTS: Twenty-nine study participants were enrolled and staged with T1 (n = 3), T2 (n = 7), T3 (n = 14), or T4 disease (n = 5). Three-year overall survival rates were 69% for T1/2 disease, 79% for T3 disease, and 0% for T4 disease. Three-year local control rates were 70% for T1/2 disease, 50% for T3 disease, and 20% for T4 disease. Grade 2 or higher dermatitis or soft-tissue necrosis occurred more frequently in study patients treated with boluses (8/14 vs 2/15; P = .02). Salvage treatment was safely performed for 12 recurrent cases. CONCLUSIONS: These results suggest that SRT outcomes are promising for patients with ear cancer (? T3 disease). The rate of toxicity was acceptable in the study patients treated without boluses. Outcomes of salvage surgery and postoperative radiotherapy following SRT were also encouraging. PMID- 27556673 TI - How Can Physicians Educate Patients About Health Care Policy Issues? AB - Complicated health care policy decisions are generally made by elected officials. The officials making these complicated decisions are elected by the people, and citizens' participation in the voting process is one of the basic tenets of democracy. Voters in the United States, who are also patients in the health care system, receive enormous amounts of information throughout election cycles. This information is generally delivered in sound bites often intended to elicit an emotional reaction rather than simply inform. From April through July 2016, the author-an academic physician-rode a bicycle across the United States and met with people in small rural towns to ask them their understanding of the Affordable Care Act and the impact it has had on their lives. In this Commentary the author shares some of those stories, which are often informed by sound bites and misinformation. The author argues that it is the role of academic physicians to educate not only students and residents but also patients. In addition to providing information about patients' medical problems, physicians can educate them about the health care policy issues that are decided by elected officials.A doctor can help educate patients about these issues to facilitate their making informed decisions in elections. Physicians have a role and responsibility in society as a knowledgeable person to make the health care system be the best it can be for the most people. PMID- 27556674 TI - Closing the Health Care Gap in Communities: A Safety Net System Approach. AB - The goal of U.S. health care should be good health for every American. This daunting goal will require closing the health care gap in communities with a particular focus on the most vulnerable populations and the safety net institutions that disproportionately serve these communities. This Commentary describes Denver Health's (DH's) two-pronged approach to achieving this goal: (1) creating an integrated system that focuses on the needs of vulnerable populations, and (2) creating an approach for financial viability, quality of care, and employee engagement. The implementation and outcomes of this approach at DH are described to provide a replicable model. An integrated delivery system serving vulnerable populations should go beyond the traditional components found in most integrated health systems and include components such as mental health services, school-based clinics, and correctional health care, which address the unique and important needs of, and points of access for, vulnerable populations. In addition, the demands that a safety net system experiences from an open-door policy on access and revenue require a disciplined approach to cost, quality of care, and employee engagement. For this, DH chose Lean, which focuses on reducing waste to respect the patients and employees within its health system, as well as all citizens. DH's Lean effort produced almost $195 million of financial benefit, impressive clinical outcomes, and high employee engagement. If this two-pronged approach were widely adopted, health systems across the United States would improve their chances of giving better care at costs they can afford for every person in society. PMID- 27556675 TI - Team Mentoring for Interdisciplinary Team Science: Lessons From K12 Scholars and Directors. AB - PURPOSE: Mentoring is critical for academic success. As science transitions to a team science model, team mentoring may have advantages. The goal of this study was to understand the process, benefits, and challenges of team mentoring relating to career development and research. METHOD: A national survey was conducted of Building Interdisciplinary Research Careers in Women's Health (BIRCWH) program directors-current and former scholars from 27 active National Institutes of Health (NIH)-funded BIRCWH NIH K12 programs-to characterize and understand the value and challenges of the team approach to mentoring. Quantitative data were analyzed descriptively, and qualitative data were analyzed thematically. RESULTS: Responses were received from 25/27 (93%) program directors, 78/108 (72%) current scholars, and 91/162 (56%) former scholars. Scholars reported that team mentoring was beneficial to their career development (152/169; 90%) and research (148/169; 88%). Reported advantages included a diversity of opinions, expanded networking, development of stronger study designs, and modeling of different career paths. Challenges included scheduling and managing conflicting opinions. Advice by directors offered to junior faculty entering team mentoring included the following: not to be intimidated by senior mentors, be willing to navigate conflicting advice, be proactive about scheduling and guiding discussions, have an open mind to different approaches, be explicit about expectations and mentors' roles (including importance of having a primary mentor to help navigate discussions), and meet in person as a team. CONCLUSIONS: These findings suggest that interdisciplinary/interprofessional team mentoring has many important advantages, but that skills are required to optimally utilize multiple perspectives. PMID- 27556676 TI - Prevalence of temporomandibular disorders in postmenopausal women and relationship with pain and HRT. AB - The prevalence of temporomandibular disorders (TMD) is higher in females, reaching their high peak during reproductive years, probably because of the action of some female hormones, which alter pain threshold. This study aimed to investigate the prevalence of TMD in postmenopausal women and its relationship with pain and hormone replacement therapy (HRT). In total, 284 patients were evaluated and classified using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Pain was measured using the Visual Analogue Scale (VAS), and patients were also asked about the use of HRT. All data was analyzed using analysis of variance (ANOVA) and chi-square test. In total, 155 subjects did not have TMD and 129 had TMD; TMD group patients were classified according to RDC/TMD axis I classification as follows: muscle disorder group (1.6%), disk displacement group (72.87%), and arthralgia, osteoarthritis, and osteoarthrosis group (37.98%). Pain was registered in 35 patients who belonged to the TMD group, while 48 patients reported the use of HRT. There was a similar percentage of TMD and non TMD patients; moreover, the use of exogenous hormones was no associated with TMD, suggesting that there is no influence on the pain threshold. PMID- 27556677 TI - Self-reported halitosis and associated demographic and behavioral factors. AB - Halitosis is still poorly studied in young adults. The aim of this study was to evaluate the occurrence of self-reported halitosis and associate it with demographic and behavioral factors in young adult dental students. This cross sectional study was designed as a census of students enrolled in three initial and three final semesters of a dental course in a Brazilian public university. Of 284 eligible students, 257 (90.5%) completed a self-administered questionnaire. Self-reported halitosis was the primary study outcome, and was assessed with the question "do you feel you have bad breath?". Data on age, gender, frequency of tooth brushing and interproximal cleaning, tongue cleaning, mouth rinse use and dry mouth were collected using the questionnaire, and were considered independent variables. Of the students surveyed, 26.5% reported as never, 51.7% as rarely, 21.4% as sometimes, and 0.4% as always feeling they had halitosis. Morning halitosis was reported by 90.6% of those who reported halitosis. In the final multiple model, last semester students had a 55% lower chance of reporting halitosis, compared with students from the first semesters [odds ratio (OR) 0.46; 95%CI 0.24-0.89]. Women had a 2.57fold higher chance of reporting halitosis (OR = 2.57; 95%CI 1.12-5.93). Dry mouth increased the chance of self-reported halitosis 3.95-fold, compared with absence of dry mouth (OR = 3.95; 95%CI 2.03-7.68). It can be concluded that self-reports of halitosis were low among dental students, but may represent an important complaint. Gender, dry mouth and level of college education of the dentist were factors significantly associated with self-reported halitosis. PMID- 27556678 TI - Longitudinal study on clinical and microbial analysis of periodontal status in pregnancy. AB - This study was aimed to provide a longitudinal overview of the subgingival bacterial microbiome using fluorescence in situ hybridization (FISH) technique, in women in the second trimester of pregnancy (between 14 and 24 weeks), and 48 h and 8 weeks postpartum. Of 31 women evaluated during pregnancy, 24 returned for the 48-h and 18 for their 8-week exams postpartum. Probing depth (PD), bleeding on probing, clinical attachment level, and presence of calculus were recorded. Subgingival plaque samples were collected, and FISH was used to identify the numbers of eight periodontal pathogens. Friedman test was used to compare differences between follow-up examinations, followed by a multiple comparison test for a post hoc pairwise comparison. Clinically, a significantly greater number of teeth with PD = 4-5 mm were found during pregnancy than on postpartum examinations. Microbial analysis showed a statistically significant decrease in cell count over the study period for Prevotella nigrescens. P. intermedia, Campylobacter rectus, and Porphyromonas gingivalis also decrease, although not significantly, and Aggregatibacter actinomycetemcomitans increased. No significant changes were found for Fusobacterium nucleatum, Treponema denticola, or Tannerella forsythia. Our data demonstrate a change in the subgingival microbiota during pregnancy, at least for P. nigrescens. PMID- 27556679 TI - Training and calibration of interviewers for oral health literacy using the BREALD-30 in epidemiological studies. AB - The objective of this study was to describe an interviewer training and calibration method to evaluate oral health literacy using the Brazilian Rapid Estimate of Adult Literacy in Dentistry (BREALD-30) in epidemiological studies. An experienced researcher (gold standard) conducted all training sessions. The interviewer training and calibration sessions included three different phases: theoretical training, practical training, and calibration. In the calibration phase, six interviewers (dentists) independently assessed 15 videos of individuals who had different levels of oral health literacy. Accuracy and reproducibility were evaluated using the kappa coefficient and the intraclass correlation coefficient (ICC). The percentage of agreement for each word in the instrument was also calculated. After training, the kappa values were higher than 0.911 and 0.893 for intra- and inter-rater agreement, respectively. When the results were analyzed separately for the different levels of literacy, the lowest agreement rate was found when evaluating the videos of individuals with low literacy (K = 0.871), but still within the range considered to be near-perfect agreement. The ICC values were higher than 0.990 and 0.975 for intra- and inter rater agreement, respectively. The lowest percentage of agreement was 86.6% for the word "hipoplasia" (hypoplasia). This interviewer training and calibration method proved to be feasible and effective. Therefore, it can be used as a methodological tool in studies assessing oral health literacy using the BREALD 30. PMID- 27556680 TI - Prevalence of periodontopathogens and Candida spp. in smokers after nonsurgical periodontal therapy - a pilot study. AB - This pilot study aimed to evaluate the influence of smoking on clinical and microbiological parameters after nonsurgical periodontal therapy. Forty-eight subjects were grouped into smokers (SM, n = 24) and nonsmokers (NS, n = 24) and paired according to gender, age, ethnicity, and periodontal status. Both groups received oral hygiene education and scaling and root planing. Clinical evaluation was performed using plaque index (PI), bleeding on probing (BOP), pocket probing depth (PPD), gingival recession (GR), and clinical attachment level (CAL) before instrumentation (baseline) and at 3 and 6 months. The prevalence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Candida albicans, Candida glabrata, Candida tropicalis, and Candida dubliniensis in subgingival biofilm was determined by polymerase chain reaction. The data were statistically analyzed considering p < 0.05. Clinical conditions improved between baseline and 3 months after periodontal treatment. However, NS had a better clinical response, presenting greater PPD reduction and CAL increase in comparison to SM. Periodontal treatment reduced the levels of P. gingivalis, A. actinomycetemcomitans, and T. forsythia individually after 3 months for the NS group and after 6 months for both groups. The prevalence of Candida species was markedly higher in SM than in NS at all time points evaluated. Periodontopathogens associated or not with C. albicans or C. dubliniensis were more prevalent in SM than in NS at baseline and after 3 months. It was concluded that smoking impairs clinical and microbiological responses to periodontal therapy. Periodontopathogens combined or not with some Candida species are resistant to short-term periodontal therapy in SM. PMID- 27556681 TI - Agreement between clinical and histopathologic diagnoses and completeness of oral biopsy forms. AB - The present study aimed to assess the rate of agreement between clinical and histopathological diagnoses and to report the frequency of completed forms for specimens that were subjected to histopathological examination and retrospectively examined. Data from 8,168 specimens submitted to histopathological examination were retrieved from the records. A total of 5,368 cases were included. Agreement was defined based on the definition of lesion nature according to its diagnostic category. Sensitivity, specificity, and positive and negative predictive values were calculated for each diagnostic category. The highest rate of agreement was observed for periapical lesions (92.6%), followed by potentially malignant disorders (90.1%) and non-neoplastic proliferative disorders (89.3%). Low rates of histopathological confirmation of the clinical impression were observed for mesenchymal tumors (25.0%) and cysts (44.2%). Sensitivity values were > 0.70 for all lesions, except for cysts (0.51). Specificity was relatively high, ranging from 0.97 to 1.00. The frequency of incomplete biopsy forms ranged from 16.8% (malignant tumors of oral mucosal epithelium) to 51.0% (nonspecific inflammatory reaction). The most frequently completed biopsy forms corresponded to epithelial malignant tumors (83.2%) and glandular inflammation (72.3%). In conclusion, there was an acceptable level of agreement. The low level of completeness of biopsy forms indicates little awareness about the relevance of gathering detailed information during clinical examination. PMID- 27556682 TI - Tumor-associated macrophages (TAMs): clinical-pathological parameters in squamous cell carcinomas of the lower lip. AB - The objective of this study was to analyze the presence of tumor-associated macrophage (TAM) subpopulations M1 and M2 in squamous cell carcinoma of the lower lip (SCCLL) by immunohistochemitry, and to evaluate the possible role of these subtypes in the development of regional lymph node metastasis and their association with clinical and pathological parameters. Forty-two cases of SCCLL were divided into two groups (21 with and 21 without regional lymph node metastasis). The histopathological grade of malignancy was determined and the material was submitted to double staining with anti-CD68/anti-CD163 and anti CD68/anti-HLA-DR monoclonal antibodies. The results were analyzed statistically using the Wilcoxon signed-rank and Spearman correlation tests. The M1 and M2 subpopulations were observed in all cases studied. No significant difference was observed between the quantities of M1 and M2 TAMs regarding tumor size (p > 0.05). A significantly larger number of M2 compared to M1 TAMs was observed in tumors without regional lymph node metastasis, tumors in early stages, and low grade tumors (p < 0.05). No significant difference between the numbers of M1 and M2 TAMs was observed in tumors with regional lymph node metastasis, tumors in advanced stages, and high-grade tumors (p > 0.05). There was a positive weak correlation between M1 and M2 TAMs (r = 0.361; p = 0.019). The results suggest a more important role of M2 TAMs in early stages than advanced stages of lip carcinogenesis. The progression of SCCLL does not seem to be related to an imbalance of macrophage polarization in the microenvironment of these tumors. PMID- 27556683 TI - The relevance of clinical and radiographic features of jaw lesions: A prospective study. AB - The study was carried out in a Brazilian population and the aim was to describe the prevalence and the clinic-radiographical features of jaw lesions. In addition, a comparison between the main diagnosis hypothesis and final diagnosis was accessed. A prospective study which evaluated all patients with jaw lesions diagnosed in an Oral Diagnosis Center, between August 2013 and October 2014. A total of 450 patients were observed for the first time, and 130 had some type of jaw lesion. The mean age of the patients was 35.2 years +/- 17.86. Among these, 71 were women (54.62%) and 87 were Caucasian (66.92%). The mandible was affected more frequently (71.43%) than the maxilla (28.57%). Swelling and pain were the most frequent clinical signs and symptoms and were observed in 60 (42.85%) and 38 (27.14%) cases, respectively. The panoramic x-ray was the main radiographic exam utilized (88.57%). Radiolucent lesions accounted for 89 cases (63.57%) and the unilocular form was present in 114 cases (81.43%). A total of 93 cases had histopathological analyses and the periapical cyst was the most frequent lesion. In the other 47 lesions, the diagnosis was conducted by clinical and radiographic management. Bone lesions were frequent, being noted on first visit in approximately 30% of patients; in 1/3 of the cases, the diagnoses were completed with a combination of clinical and radiographic exams. PMID- 27556684 TI - Experimental osteonecrosis: development of a model in rodents administered alendronate. AB - The main objective of this study was to cause bisphosphonate-related osteonecrosis of the jaws to develop in a rodent model. Adult male Holtzman rats were assigned to one of two experimental groups to receive alendronate (AL; 1 mg/kg/week; n = 6) or saline solution (CTL; n = 6). After 60 days of drug therapy, all animals were subjected to first lower molar extraction, and 28 days later, animals were euthanized. All rats treated with alendronate developed osteonecrosis, presenting as ulcers and necrotic bone, associated with a significant infection process, especially at the inter-alveolar septum area and crestal regions. The degree of vascularization, the levels of C-telopeptide cross linked collagen type I and bone-specific alkaline phosphatase, as well as the bone volume were significantly reduced in these animals. Furthermore, on radiographic analysis, animals treated with alendronate presented evident sclerosis of the lamina dura of the lower first molar alveolar socket associated with decreased radiographic density in this area. These findings indicate that the protocol developed in the present study opens new perspectives and could be a good starting model for future property design. PMID- 27556685 TI - Gate Switchable Transport and Optical Anisotropy in 90 degrees Twisted Bilayer Black Phosphorus. AB - Anisotropy describes the directional dependence of a material's properties such as transport and optical response. In conventional bulk materials, anisotropy is intrinsically related to the crystal structure and thus not tunable by the gating techniques used in modern electronics. Here we show that, in bilayer black phosphorus with an interlayer twist angle of 90 degrees , the anisotropy of its electronic structure and optical transitions is tunable by gating. Using first principles calculations, we predict that a laboratory-accessible gate voltage can induce a hole effective mass that is 30 times larger along one Cartesian axis than along the other axis, and the two axes can be exchanged by flipping the sign of the gate voltage. This gate-controllable band structure also leads to a switchable optical linear dichroism, where the polarization of the lowest-energy optical transitions (absorption or luminescence) is tunable by gating. Thus, anisotropy is a tunable degree of freedom in twisted bilayer black phosphorus. PMID- 27556686 TI - Relationship of health locus of control with specific health behaviours and global health appraisal: a meta-analysis and effects of moderators. AB - Health locus of control (HLOC) refers to beliefs regarding how one's health is influenced by oneself, others, or fate. This meta-analysis investigated whether three HLOC dimensions (internality/I-HLOC, powerful others/P-HLOC, chance/C-HLOC) were related to both specific health behaviours and global health appraisal, and whether these relationships were moderated by gender and age compositions, individualism, and power distance. Three-level mixed-effects meta-analysis was performed on studies examining the associations of HLOC with specific health behaviour (k = 76, N = 76,580, 57% women, Mage = 43.75) and global health appraisal (k = 95, N = 12,068, 57% women, Mage = 45.44), respectively. For specific health behaviour, the averaged correlations with the HLOC dimensions were generally weak (r's = -.07 to .10). However, the links between P-HLOC and exercise were moderated by all four demographic moderators, and gender composition and individualism moderated the association between the HLOC dimensions and diet. For global health appraisal, all of the averaged correlations were statistically significant (r's = -.16 to .21), except that between P-HLOC and mental quality of life. The results further showed individualism and power distance to moderate the links between the HLOC dimensions and both mental and physical quality of life, and gender composition to moderate those between these dimensions and two indicators of emotional problems (depression and anxiety). PMID- 27556687 TI - Multiple biopsy passes and the risk of complications of percutaneous liver biopsy. AB - BACKGROUND AND AIM: To minimize the sample variability of liver biopsy, the tissue length should be at least 25 mm. Consequently, more than one biopsy pass is needed with cutting biopsy needles. We aimed to investigate the risk factors of biopsy-related complication, including the number of biopsy passes. METHODS: All consecutive liver biopsies performed between 2005 and 2014 were included. Biopsies were ultrasound assisted and performed with cutting biopsy needles. A complication was an event where the patient visited a healthcare provider because of biopsy-related complaints. Complications followed by hospitalization 2 or more days or intervention were considered severe. RESULTS: In total, 1806 liver biopsies were analyzed. Overall, 102 (5.6%) complications were observed, of which 31 (1.7%) were severe. One (0.06%) patient died. Common complications were pain (n=75/102; 74%) and bleeding (n=34/102; 33%). Two biopsy passes were not associated with an increased risk of complications compared with one biopsy pass [odds ratio (OR): 1.59; 95% confidence interval (CI): 0.83-3.04; P=0.16], whereas three or more biopsy passes increased this risk compared with one (OR: 2.97; 95% CI: 1.38-6.42; P=0.005) or two biopsy passes (OR: 1.87; 95% CI: 1.10-3.19; P=0.021). The risk of severe complications was not influenced by the number of biopsy passes (P>0.24). Hepatic malignancy (OR: 3.21; 95% CI: 1.18-8.73; P=0.022) and international normalized ratio 1.4 or more (OR: 7.03; 95% CI: 2.74-18.08; P<0.001) were risk factors of severe complications. CONCLUSION: Severe complication rate and mortality were low. Performing multiple biopsy passes was not associated with severe complications, whereas hepatic malignancy or elevated international normalized ratio were associated with an increased risk. PMID- 27556688 TI - The utility and yield of endoscopic ultrasonography for suspected choledocholithiasis in common gastroenterology practice. AB - BACKGROUND AND STUDY AIM: Endoscopic ultrasonography (EUS) is an established diagnostic modality for diagnosing common bile duct (CBD) stones. Its use has led to a reduction in the number of endoscopic retrograde cholangiopancreatography (ERCP) procedures performed for suspected choledocholithiasis. We aimed to explore the role of EUS in detecting CBD stones and/or sludge in common gastroenterology practice. PATIENTS AND METHODS: We reviewed case records of 268 consecutive patients who underwent (EUS) procedures performed to confirm or rule out the presence of CBD stones and/or sludge between November 2006 and January 2011 in the Reinier de Graaf Hospital, Delft, The Netherlands, which is a nonacademic community hospital. RESULTS: On the basis of EUS findings, 169 of 268 (63%) patients did not undergo ERCP and were therefore not exposed to its risk of complications. Patients with positive findings on EUS (n=99) all underwent ERCP and endoscopic sphincterotomy. Only 57 of 99 (58%) had positive findings at ERCP. The main contributing factors to this finding seem to be time interval between EUS and ERCP and the type of CBD content (i.e. sludge, one CBD stone or more than one CBD stone) described. CONCLUSION: In our common gastroenterology practice, EUS plays an important role in selecting patients suspected to have CBD stones or sludge for ERCP. Much is to be learned about the probability of spontaneous passage of CBD stones and sludge into the duodenum. PMID- 27556689 TI - Improving spatial prioritisation for remote marine regions: optimising biodiversity conservation and sustainable development trade-offs. AB - Creating large conservation zones in remote areas, with less intense stakeholder overlap and limited environmental information, requires periodic review to ensure zonation mitigates primary threats and fill gaps in representation, while achieving conservation targets. Follow-up reviews can utilise improved methods and data, potentially identifying new planning options yielding a desirable balance between stakeholder interests. This research explored a marine zoning system in north-west Australia-a biodiverse area with poorly documented biota. Although remote, it is economically significant (i.e. petroleum extraction and fishing). Stakeholder engagement was used to source the best available biodiversity and socio-economic data and advanced spatial analyses produced 765 high resolution data layers, including 674 species distributions representing 119 families. Gap analysis revealed the current proposed zoning system as inadequate, with 98.2% of species below the Convention on Biological Diversity 10% representation targets. A systematic conservation planning algorithm Maxan provided zoning options to meet representation targets while balancing this with industry interests. Resulting scenarios revealed that conservation targets could be met with minimal impacts on petroleum and fishing industries, with estimated losses of 4.9% and 7.2% respectively. The approach addressed important knowledge gaps and provided a powerful and transparent method to reconcile industry interests with marine conservation. PMID- 27556690 TI - Ataxia-telangiectasia mutated activation mediates tumor necrosis factor-alpha induced MMP-13 up-regulation and metastasis in lung cancer cells. AB - Despite that ataxia-telangiectasia mutated (ATM) is involved in IL-6 promoted lung cancer chemotherapeutic resistance and metastasis, the exact role of ATM in tumor necrosis factor-alpha (TNF-alpha) increasing tumor migration is still elusive. In the present study, we demonstrated that TNF-alpha promoted lung cancer cell migration by up-regulation of matrix metalloproteinase-13 (MMP-13). Notably, by gene silencing or kinase inhibition, we proposed for the first time that ATM is a key up-stream regulator of TNF-alpha activated ERK/p38-NF-kappaB pathway. The existence of TNF-alpha secreted in autocrine or paracrine manner by components of tumor microenvironment highlights the significance of TNF-alpha in inflammation-associated tumor metastasis. Importantly, in vivo lung cancer metastasis test showed that ATM depletion actually reduce the number of metastatic nodules and cancer nests in lung tissues, verifying the critical role of ATM in metastasis. In conclusion, our findings demonstrate that ATM, which could be activated by lung cancer-associated TNF-alpha, up-regulate MMP-13 expression and thereby augment tumor metastasis. Therefore, ATM might be a promising target for prevention of inflammation-associated lung cancer metastasis. PMID- 27556691 TI - A polymorphism rs4705341 in the flanking region of miR-143/145 predicts risk and prognosis of colorectal cancer. AB - The aim of this study was to investigate the effect of a polymorphism rs4705341 in the flanking region of miR-143/145 on the risk of colorectal cancer (CRC). The rs4705341 polymorphism was analyzed in 1002 cases and 1062 controls using a polymerase chain reaction-restriction fragment length polymorphism method. We found a significantly reduced CRC susceptibility with miR-143/145 rs4705341 in homozygote comparison (adjusted OR = 0.66, 95%CI, 0.50-0.88, P = 0.004), dominant genetic model (adjusted OR = 0.80, 95%CI, 0.67-0.96, P = 0.015), recessive genetic model (adjusted OR = 0.73, 95%CI, 0.56-0.94, P = 0.016), and allele comparison (adjusted OR = 0.83, 95%CI, 0.73-0.94, P = 0.004). Stratification analysis showed that the rs4705341 was related to differentiated status, clinical stage I-II, and patients without lymph node metastasis. Moreover, patients with rs4705341GG had a longer overall survival (adjusted HR = 5.57, 95%CI, 0.95 32.68). These findings indicate that the miR-143/145 rs4705341 may be used as a potential biomarker for the development and prognosis of CRC. PMID- 27556693 TI - Association mining of mutated cancer genes in different clinical stages across 11 cancer types. AB - Many studies have demonstrated that some genes (e.g. APC, BRAF, KRAS, PTEN, TP53) are frequently mutated in cancer, however, underlying mechanism that contributes to their high mutation frequency remains unclear. Here we used Apriori algorithm to find the frequent mutational gene sets (FMGSs) from 4,904 tumors across 11 cancer types as part of the TCGA Pan-Cancer effort and then mined the hidden association rules (ARs) within these FMGSs. Intriguingly, we found that well known cancer driver genes such as BRAF, KRAS, PTEN, and TP53 were often co occurred with other driver genes and FMGSs size peaked at an itemset size of 3~4 genes. Besides, the number and constitution of FMGS and ARs differed greatly among different cancers and stages. In addition, FMGS and ARs were rare in endocrine-related cancers such as breast carcinoma, ovarian cystadenocarcinoma, and thyroid carcinoma, but abundant in cancers contact directly with external environments such as skin melanoma and stomach adenocarcinoma. Furthermore, we observed more rules in stage IV than in other stages, indicating that distant metastasis needed more sophisticated gene regulatory network. PMID- 27556692 TI - Chk1 inhibition significantly potentiates activity of nucleoside analogs in TP53 mutated B-lymphoid cells. AB - Treatment options for TP53-mutated lymphoid tumors are very limited. In experimental models, TP53-mutated lymphomas were sensitive to direct inhibition of checkpoint kinase 1 (Chk1), a pivotal regulator of replication. We initially tested the potential of the highly specific Chk1 inhibitor SCH900776 to synergize with nucleoside analogs (NAs) fludarabine, cytarabine and gemcitabine in cell lines derived from B-cell malignancies. In p53-proficient NALM-6 cells, SCH900776 added to NAs enhanced signaling towards Chk1 (pSer317/pSer345), effectively blocked Chk1 activation (Ser296 autophosphorylation), increased replication stress (p53 and gamma-H2AX accumulation) and temporarily potentiated apoptosis. In p53-defective MEC-1 cell line representing adverse chronic lymphocytic leukemia (CLL), Chk1 inhibition together with NAs led to enhanced and sustained replication stress and significantly potentiated apoptosis. Altogether, among 17 tested cell lines SCH900776 sensitized four of them to all three NAs. Focusing further on MEC-1 and co-treatment of SCH900776 with fludarabine, we disclosed chromosome pulverization in cells undergoing aberrant mitoses. SCH900776 also increased the effect of fludarabine in a proportion of primary CLL samples treated with pro-proliferative stimuli, including those with TP53 disruption. Finally, we observed a fludarabine potentiation by SCH900776 in a T-cell leukemia 1 (TCL1)-driven mouse model of CLL. Collectively, we have substantiated the significant potential of Chk1 inhibition in B-lymphoid cells. PMID- 27556694 TI - Lactoferrin selectively triggers apoptosis in highly metastatic breast cancer cells through inhibition of plasmalemmal V-H+-ATPase. AB - Breast cancer is the most common type of cancer affecting women. Despite the good prognosis when detected early, significant challenges remain in the treatment of metastatic breast cancer. The recruitment of the vacuolar H+-ATPase (V-H+-ATPase) to the plasma membrane, where it mediates the acidification of the tumor microenvironment (TME), is a recognized feature involved in the acquisition of a metastatic phenotype in breast cancer. Therefore, inhibitors of this pump have emerged as promising anticancer drugs. Lactoferrin (Lf) is a natural pro apoptotic iron-binding glycoprotein with strong anticancer activity whose mechanism of action is not fully understood. Here, we show that bovine Lf (bLf) preferentially induces apoptosis in the highly metastatic breast cancer cell lines Hs 578T and MDA-MB-231, which display a prominent localisation of V-H+ ATPase at the plasma membrane, but not in the lowly metastatic T-47D or in the non-tumorigenic MCF-10-2A cell lines. We also demonstrate that bLf decreases the extracellular acidification rate and causes intracellular acidification in metastatic breast cancer cells and, much like the well-known proton pump inhibitors concanamycin A and bafilomycin A1, inhibits V-H+-ATPase in sub cellular fractions. These data further support that bLf targets V-H+-ATPase and explain the selectivity of bLf for cancer cells, especially for highly metastatic breast cancer cells. Altogether, our results pave the way for more rational in vivo studies aiming to explore this natural non-toxic compound for metastatic breast cancer therapy. PMID- 27556695 TI - PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-alpha expression levels. AB - PADI4 (peptidyl deiminase isoform 4) is overexpressed in many tumor tissues and converts arginine residues to citrulline residues. This study used an Illumina SNP microarray and a TaqMan assay to determine the possible association of the PADI4 gene with various tumor risks. Both genotyping methods demonstrated significant associations between the tag SNPs rs1635566 and rs882537 in the PADI4 locus with gastric carcinoma in two independent cohorts. Based on this genotyping result, we used the Cancer Pathway Finder, p53 Signaling, Signal Transduction and Tumor Metastasis PCR arrays to investigate the tumorigenic pathway of PADI4 in MNK-45 cells derived from gastric carcinoma. We detected significantly decreased expression levels of CXCR2, KRT14 and TNF-alpha in MNK-45 cells that were treated with anti-PADI4 siRNA. We also detected increased expression of these three genes in MNK-45 cells transfected with a pcDNA3.1 plasmid overexpressing PADI4. A highly similar result was also obtained for SGC 7901 cells, which also originate from gastric carcinoma. Our result indicates that the PADI4 gene has genetic susceptibility in gastric carcinoma. PADI4 contributes to gastric tumorigenesis by upregulating CXCR2, KRT14 and TNF-alpha expression, which are well known to activate angiogenesis, cell proliferation, cell migration and the immune microenvironment in tumors. PMID- 27556696 TI - Knockdown of NEAT1 restrained the malignant progression of glioma stem cells by activating microRNA let-7e. AB - Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA, promotes oncogenesis in various tumors, including human gliomas. Herein, we studied the expression and function of NEAT1 in glioma stem cells (GSCs). Quantitative real-time PCR demonstrated that NEAT1 was upregulated in GSCs. NEAT1 knockdown inhibited GSC cell proliferation, migration and invasion and promoted GSC apoptosis. A potential binding region between NEAT1 and microRNA let-7e was confirmed by dual-luciferase assays. Upregulation of NEAT1 reduced the expression of let-7e, and there was reciprocal repression between NEAT1 and let-7e in an Argonaute 2-dependent manner. Let-7e expression was lower expression in glioblastoma tissues and GSCs than in normal brain tissues and cells. Restoration of let-7e suppressed tumor function by inhibiting proliferation, migration and invasion while promoting apoptosis in GSCs. NEAT1 knockdown and let-7e overexpression both reduced NRAS protein expression. NRAS was identified as a direct target of let-7e and promoted oncogenesis in GSCs. As NEAT1 promoted oncogenesis by downregulating let-7e expression, both of these genes could be considered for application in glioma therapy. PMID- 27556697 TI - Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. AB - Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer. PMID- 27556698 TI - TIPE2 suppresses angiogenesis and non-small cell lung cancer (NSCLC) invasiveness via inhibiting Rac1 activation and VEGF expression. AB - Non-small cell lung cancer (NSCLC) is one of the leading causes of all cancer related deaths worldwide. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly introduced negative immune regulator, which also controls tumorigenesis. However, the role of TIPE2 in angiogenesis is unknown. In the present study, we investigated the expression and roles of TIPE2 in NSCLC. TIPE2 upregulation in human NSCLC tissues was negatively associated with the primary tumor size, lymph node metastasis, and advanced clinical stage, which can be used to predict lymph node metastasis. Moreover, overexpression of TIPE2 not only inhibited the colony formation, migration, and invasion of NSCLC cells but also indirectly suppressed the proliferation, migration, and tube formation of vascular endothelial cells. Furthermore, TIPE2 suppressed tumor invasiveness and angiogenesis via inhibiting the activation of Rac1 and subsequently weakening its downstream effects, including F-actin polymerization and VEGF expression. Collectively, these results indicate that TIPE2 plays a key role in NSCLC metastasis, suggesting that forced TIPE2 expression might be a novel strategy for the treatment of NSCLC. PMID- 27556699 TI - Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation. AB - Alternating electric fields at an intermediate frequency (100~300 kHz), referred to as tumour-treating fields (TTF), are believed to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the existence of an antimitotic effect of TTF is widely known, the proposed apoptotic mechanism of TTF on cell function and the efficacy of TTF are controversial issues among medical experts. To resolve these controversial issues, a better understanding of the underlying molecular mechanisms of TTF on cell function and the differences between the effects of TTF alone and in combination with other treatment techniques is essential. Here, we report experimental evidence of TTF-induced apoptosis and the synergistic antimitotic effect of TTF in combination with ionizing radiation (IR). For these experiments, two human Glioblastoma multiforme (GBM) cells (U373 and U87) were treated either with TTF alone or with TTF followed by ionizing radiation (IR). Cell apoptosis, DNA damage, and mitotic abnormalities were quantified after the application of TTF, and their percentages were markedly increased when TTF was combined with IR. Our experimental results also suggested that TTF combined with IR synergistically suppressed both cell migration and invasion, based on the inhibition of MMP-9 and vimentin. PMID- 27556700 TI - Identification of breast cancer cell subtypes sensitive to ATG4B inhibition. AB - Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2 negative breast cancer cells, require ATG4B to survive under stress. In HER2 positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies. PMID- 27556701 TI - Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence. AB - OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. EXPERIMENTAL DESIGN: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Next-generation sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. RESULTS: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3%) and in cfDNA and metastatic tumor samples from one patient (100%). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. CONCLUSIONS: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC. PMID- 27556702 TI - Induction of exportin-5 expression during melanoma development supports the cellular behavior of human malignant melanoma cells. AB - Regulation of gene expression via microRNAs is known to promote the development of many types of cancer. In melanoma, miRNAs are globally up-regulated, and alterations of miRNA-processing enzymes have already been identified. However, mis-regulation of miRNA transport has not been analyzed in melanoma yet. We hypothesized that alterations in miRNA transport disrupt miRNA processing. Therefore, we investigated whether the pre-miRNA transporter Exportin-5 (XPO5) was involved in altered miRNA maturation and functional consequences in melanoma. We found that XPO5 is significantly over-expressed in melanoma compared with melanocytes. We showed enhanced XPO5 mRNA stability in melanoma cell lines which likely contributes to up-regulated XPO5 protein expression. In addition, we identified MEK signaling as a regulator of XPO5 expression in melanoma. Knockdown of XPO5 expression in melanoma cells led to decreased mature miRNA levels and drastic functional changes. Our data revealed that aberrant XPO5 expression is important for the maturation of miRNAs and the malignant behavior of melanoma cells. We suggest that the high abundance of XPO5 in melanoma leads to enhanced survival, proliferation and metastasis and thereby supports the aggressiveness of melanoma. PMID- 27556703 TI - Generation of TALEN-mediated FH knockout rat model. AB - Transcription activator-like effector nucleases (TALENs) are valuable tools for precise genome engineering of laboratory animals. Here we utilized this technique for efficient site-specific gene modification to create a fumarate hydratase (FH) gene knockout rat model, in which there was an 11 base-pair deletion in the first exon of the FH gene in 111 rats. 18 live-born targeted mutation offsprings were produced from 80 injected zygotes with 22.5% efficiency, indicating high TALEN knockout success in rat zygots. Only heterozygous deletion was observed in the offsprings. Sixteen pairs of heterozygous FH knockout (FH+/-) rats were arranged for mating experiments for six months without any homozygous KO rat identified. Sequencing from the pregnant rats embryo samples showed no homozygous FH KO, indicating that homozygous FH KO is embryonically lethal. Comparatively, the litter size was decreased in both male and female FH+/- KO rats. There was no behaviour difference between the FH+/- KO and the control rats except that the FH+/- KO male rats showed significantly higher body weight in the 16-week observation period. Clinical haematology and biochemical examinations showed hematopoietic and kidney dysfunction in the FH+/- KO rats. Small foci of anaplastic lesions of tubular epithelial cells around glomeruli were identified in the FH+/- kidney, and these anaplastic cells were comparatively positive for Ki67, p53 and Sox9, and such findings are most probably related to the kidney dysfunction reflected by the biochemical examinations of the rats. In conclusion, we have successfully established an FH+/- KO rat model, which will be useful for further functional FH studies. PMID- 27556705 TI - Myeloma minimal residual disease testing in the United States: Evidence of improved standardization. PMID- 27556706 TI - ICNP (r): a standardized terminology to describe professional nursing practice. PMID- 27556707 TI - Maternal and neonatal factors related to prematurity. AB - OBJECTIVE: To identify maternal and neonatal factors associated with prematurity in the municipality of Porto Alegre. METHOD: This was a population-based case control study. The cases were newborns under 37 weeks of gestation and the controls were newborns over 37 weeks. The data came from the records of 19,457 births in the city of Porto Alegre in the year 2012 from the Information System on Live Births of the Municipal Health Department. The analysis was carried outand adjusted by a Logistic Regression according to a hierarchical model. The variables studied were allocated into three hierarchy levels: sociodemographic variables; reproductive history; and gestational and birth factors. RESULTS: There were 767 cases allocated and 1,534 controls in a design of a case for two controls (1:2) by simple randomization. In the final model, a statistically significant association was found for prematurity for the following variables: mother's age under 19 years old (OR=1.32; CI 95%: 1.02-1.71) or over 34 years old (OR=1.39; CI 95%: 1.12-1.72); inadequate maternal schooling for age (OR=2.11; CI 95%: 1.22-3.65); multiple pregnancies (OR=1.14; CI 95%: 1.01-1.29); C-section (OR=1.15; CI 95%: 1.03-1.29); birth weights under 2,500g (OR=4.04; CI 95%: 3.64 4.49); Apgar score at five minutes between zero and three (OR=1.47; CI 95%: 1.12 1.91); and inadequate prenatal care (OR=1.18; CI 95%: 1.02-1.36). CONCLUSION: The present study showed the most immediate consequence of prematurity for newborns by evidencing its association with worse Apgar scores and low birth weight. The following factors were also shown as possible more distal determinants of prematurity: mother's age; inadequate maternal education; multiple gestation; inadequate prenatal care; and C-section. OBJETIVO: Identificar fatores maternos e neonatais associados a prematuridade no municipio de Porto Alegre. METODO: Estudo do tipo caso-controle de base populacional. Os casos foram recem-nascidos com menos de 37 semanas de gestacao, e os controles foram os recem-nascidos com 37 semanas ou mais. Os dados provieram dos registros de 19.457 nascimentos do municipio de Porto Alegre, no ano de 2012, no Sistema de Informacoes sobre Nascidos Vivos da Secretaria Municipal da Saude. Foi realizada analise ajustada mediante Regressao Logistica segundo modelo hierarquico. As variaveis estudadas foram alocadas em tres niveis de hierarquia: variaveis sociodemograficas; historia reprodutiva; fatores gestacionais e de nascimento. RESULTADOS: Foram alocados 767 casos e 1.534 controles, em um desenho de um caso para dois controles (1:2), mediante randomizacao simples. No modelo final, foi encontrada associacao estatisticamente significante para prematuridade para as seguintes variaveis: idade materna menor que 19 anos (OR=1,32; IC 95%: 1,02 - 1,71) e maior que 34 anos (OR=1,39; IC 95%: 1,12 - 1,72); escolaridade materna inadequada para a idade (OR=2,11; IC 95%: 1,22 - 3,65); gravidez multipla (OR=1,14; IC 95%: 1,01 1,29); cesariana (OR=1,15; IC 95%: 1,03 - 1,29); peso ao nascer menor a 2.500g (OR=4,04; IC 95%: 3,64 - 4,49); Indice de Apgar no 5 degrees minuto de zero a tres (OR=1,47; IC 95%: 1,12 - 1,91) e pre-natal inadequado (OR=1,18; IC 95%: 1,02 - 1,36). CONCLUSAO: O presente estudo evidenciou as consequencias mais imediatas da prematuridade para os recem-nascidos ao revelar sua associacao com piores escores de Apgar e baixo peso ao nascimento. Mostrou como possiveis determinantes mais distais de prematuridade: idade materna, educacao materna inadequada, gestacao multipla, pre-natal inadequado e realizacao de cesariana. PMID- 27556708 TI - Mortality among children under the age of one: analysis of cases after discharge from maternity. AB - OBJECTIVE: To analyze infant death after discharge from maternity in the time period between 2000 and 2013. METHOD: A cross-sectional retrospective quantitative study in a municipality northward in the state of Parana. Data were analyzed using the SPSS(r), and were subjected to Chi-square test, logistical regression, 95% confidence interval, and a significance level of p <0.05. RESULTS: Two hundred forty-nine children were born, discharged from maternity and subsequently died; 10.1% in the neonatal period and 89.9% in the post-neonatal period. Pregnancy follow-up, birth, and child monitoring took place mainly in the public health system. There was a statistically significant association between the infant component and place of delivery (p =0.002; RR=1.143; IC95%=1.064 1.229), and a lower number of childcare medical visits (p =0.001; RR=1.294; IC95%=1.039-1.613). The causes of death in the neonatal period were perinatal conditions (40%); external causes (32%); and congenital malformations (20%). In the post-neonatal period, congenital malformations (29.9%), external causes (24.1%); and infectious-parasitic diseases (11.2%) were the causes of death. CONCLUSION: Virtually all children were born in conditions of good vitality that were worsened due to potentially preventable diseases that led to death. OBJETIVO: Analisar as mortes infantis apos alta das maternidades ocorridas entre 2000 e 2013. METODO: Pesquisa quantitativa retrospectiva transversal, em municipio no norte do Parana. Os dados foram analisados no SPSS(r). .Aplicaram-se teste qui-quadrado, regressao logistica, intervalo de confianca 95% e nivel de significancia p <0,05. RESULTADOS: 249 criancas nasceram, receberam alta e evoluiram para obito, 10,1% no periodo neonatal e 89,9% no pos-neonatal. O acompanhamento gestacional, nascimento e seguimento da crianca ocorreram, predominantemente, no servico publico. Houve associacao estatisticamente significativa entre componente infantil e local de parto (p =0,002; RR=1,143; IC95%=1,064-1,229); realizar menos consultas de puericultura (p =0,001; RR=1,294; IC95%=1,039-1,613). As causas de morte no periodo neonatal foram afeccoes perinatais (40%), causas externas (32%) e malformacoes congenitas (20%). No pos neonatal, malformacoes congenitas (29,9%), causas externas (24,1%) e doencas infectoparasitarias (11,2%). CONCLUSAO: A quase totalidade das criancas nasceu em boas condicoes de vitalidade, apresentou agravos por doencas potencialmente preveniveis que culminaram no obito. PMID- 27556704 TI - Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit beta-Arrestin-2. AB - Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology. Herein, we report the pharmacology and SAR studies both in vitro and in vivo of mitragynine pseudoindoxyl (3), an oxidative rearrangement product of the corynanthe alkaloid mitragynine. 3 and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism/delta opioid receptor antagonism. In vitro, 3 and its analogs were potent agonists in [(35)S]GTPgammaS assays at the mu opioid receptor but failed to recruit beta-arrestin-2, which is associated with opioid side effects. Additionally, 3 developed analgesic tolerance more slowly than morphine, showed limited physical dependence, respiratory depression, constipation, and displayed no reward or aversion in CPP/CPA assays, suggesting that analogs might represent a promising new generation of novel pain relievers. PMID- 27556709 TI - Nurses' knowledge to identify early acute kidney injury. AB - OBJECTIVE: To evaluate the knowledgeof nurses on early identification of acute kidney injury (AKI) in intensive care, emergency and hospitalization units. METHOD: A prospective multi-center study was conducted with 216 nurses, using a questionnaire with 10 questions related to AKI prevention, diagnosis, and treatment. RESULTS: 57.2% of nurses were unable to identify AKI clinical manifestations, 54.6% did not have knowledge of AKI incidence in patients admitted to the ICU, 87.0% of the nurses did not know how to answer as regards the AKI mortality rate in patients admitted to the ICU, 67.1% answered incorrectly that slight increases in serum creatinine do not have an impact on mortality, 66.8% answered incorrectly to the question on AKI prevention measures, 60.4% answered correctly that loop diuretics for preventing AKI is not recommended, 77.6% answered correctly that AKI does not characterize the need for hemodialysis, and 92.5% said they had no knowledge of the Acute Kidney Injury Networkclassification. CONCLUSION: Nurses do not have enough knowledge to identify early AKI, demonstrating the importance of qualification programs in this field of knowledge. OBJETIVO: Avaliar o conhecimento do enfermeiro na identificacao precoce da Injuria Renal Aguda (IRA) em Unidade de Terapia Intensiva, Unidade de Internacao e Emergencia. METODO: Estudo multicentrico, prospectivo.Participaram do estudo 216 enfermeiros,por meio de questionario com 10 questoes relacionadas a prevencao, ao diagnostico e ao tratamento da IRA. RESULTADOS: 57,2% nao souberam identificar as manifestacoes clinicas da IRA, 54,6% nao tem conhecimento da incidencia de IRA em pacientes internados na UTI, 87,0% dos enfermeiros nao souberam responder ao indice de mortalidade de IRA em pacientes internados na UTI, 67,1% responderam incorretamente que aumentos discretos da creatinina serica nao tem impacto na mortalidade, 66,8% responderam incorretamente a questao sobre as medidas de prevencao da IRA, 60,4% acertaram quando responderam que nao e recomendada a utilizacao de diureticos de alca na prevencao da IRA, 77,6% acertaram ao responder que IRA nao caracteriza necessidade de hemodialise e 92,5% disseram nao conhecer a classificacao AKIN. CONCLUSAO: Enfermeiros nao tem conhecimento suficiente para a identificacao precoce da IRA, mostrando a importancia de programas de capacitacao nesta area do conhecimento. PMID- 27556710 TI - Endotoxins in surgical instruments of hip arthroplasty. AB - OBJECTIVE: To investigate endotoxins in sterilized surgical instruments used in hip arthroplasties. METHOD: A descriptive exploratory study conducted in a public teaching hospital. Six types of surgical instruments were selected, namely: acetabulum rasp, femoral rasp, femoral head remover, chisel box, flexible bone reamer and femoral head test. The selection was based on the analysis of the difficulty in removing bone and blood residues during cleaning. The sample was made up of 60 surgical instruments, which were tested for endotoxins in three different stages. The EndosafeTM Gel-Clot LAL (Limulus Amebocyte Lysate method) was used. RESULT: There was consistent gel formation with positive analysis in eight instruments, corresponding to 13.3%, being four femoral rasps and four bone reamers. CONCLUSION: Endotoxins in quantity >=0.125 UE/mL were detected in 13.3% of the instruments tested. OBJETIVO: Investigar endotoxinas em instrumentais cirurgicos esterilizados empregados em artroplastias do quadril. METODO: Estudo exploratorio, descritivo, desenvolvido em um hospital publico de ensino. Foram selecionados seis tipos de instrumentais, a saber: raspa acetabular, raspa femural, saca-cabeca de femur, formao box, fresa de femur e cabeca de prova de femur. A selecao foi feita a partir da analise da dificuldade para a remocao de residuos de sangue e osso durante a limpeza. A amostra foi constituida por 60 instrumentais cirurgicos, que foram testados para endotoxinas em tres momentos distintos. Foi utilizado o metodo de gel-clot pelo Limulus Amebocito Lisado (LAL) Endosafe(tm). RESULTADO: Houve formacao de gel consistente com analise positiva em oito instrumentais, o que corresponde a 13,3%, sendo quatro raspas de femur e quatro fresas de femur. CONCLUSAO: Foram detectadas endotoxinas em quantidade >=0,125 UE/mL em 13,3% dos instrumentais testados. PMID- 27556711 TI - Quality of life in liver transplant recipients and the influence of sociodemographic factors. AB - OBJECTIVE: To verify the influence of sociodemographic factors on the quality of life of patients after liver transplant. METHOD: Cross-sectional study with 150 patients who underwent liver transplant at a referral center. A sociodemographic instrument and the Liver Disease Quality of Life questionnaire were applied. The analysis of variance (ANOVA) was performed, as well as multiple comparisons by the Tukey test and Games-Howell tests when p <0.05. RESULTS: Old age had influence on domains of symptoms of liver disease (p = 0.049), sleep (p = 0.023) and sexual function (p = 0.03). Men showed better significant mean values than women for the loneliness dimension (p = 0.037). Patients with higher educational level had higher values for the domain of stigma of liver disease (p = 0.014). There was interference of income in the domains of quality of social interaction (p = 0.033) and stigma of the disease (p = 0.046). CONCLUSION: In half of the quality of life domains, there was influence of some sociodemographic variable. OBJETIVO: Verificar a influencia dos fatores sociodemograficos na qualidade de vida dos pacientes depois do transplante de figado. METODO: Estudo transversal, com 150 pacientes submetidos ao transplante de figado em um centro de referencia. Aplicou-se um instrumento sociodemografico e o questionario Liver Disease Quality of Life. Foi realizada Analise de Variancia (ANOVA) e comparacoes multiplas pelo teste de Tukey e Games-Howell, quando p<0,05. RESULTADOS: A idade avancada apresentou influencia nos dominios: sintomas da doenca hepatica (p=0,049), sono (p=0,023) e funcao sexual (p =0,03). Os homens apresentaram melhores medias significativas do que as mulheres na dimensao isolamento (p=0,037). Pacientes com nivel de instrucao mais alto apresentaram maiores valores no dominio estigma da doenca hepatica (p=0,014). Houve interferencia da renda nos dominios qualidade da interacao social (p=0,033) e estigma da doenca (p=0,046). CONCLUSAO: Em metade dos dominios de qualidade de vida, houve influencia de alguma variavel sociodemografica. PMID- 27556712 TI - Slips, lapses and mistakes inthe use of equipment by nurses in an intensive care unit. AB - OBJECTIVE: Toidentify the occurrence of errors in the use of equipment by nurses working in intensive careandanalyzing them in the framework of James Reason's theory of human error. METHOD: Qualitative field study in the intensive care unit of a federal hospital in the city of Rio de Janeiro. Observation and interviews were conductedwith eight nurses, from March to December 2014. Content analysis was used for the interviews, as well as the description of the scenes observed. RESULTS: Lapses of memory and attention were identified in the handling of infusion pumps, as well as planning failures during the programming of monitors. CONCLUSION: Errors cause adverse events that compromise patient safety. The authors propose creation of an instrument for daily checking of equipment, with checks throughout the work process in the programming of infusion pumps and monitors, in order to reduce failures and memory lapses. OBJETIVO: Identificar a ocorrencia de erros na utilizacao de equipamentos por enfermeiros que atuam na terapia intensiva, analisando-os a luz da teoria do erro humano de James Reason. METODO: Pesquisa de campo, qualitativa, na Unidade de Terapia Intensiva de um hospital federal do Rio de Janeiro. Realizou-se observacao e entrevista com oito enfermeiros, de marco a dezembro de 2014. Aplicou-se analise de conteudo nas entrevistas e descricao densa nas cenas observadas. RESULTADOS: Identificaram-se falhas de memoria e de atencao no manuseio das bombas infusoras e falhas de planejamento durante a programacao dos monitores. CONCLUSAO: Os erros causam eventos adversos que comprometem a seguranca do paciente. Propoe-se um instrumento de verificacao diaria dos equipamentos, com checagens ao longo do processo de trabalho da programacao das bombas infusoras e monitores, no intuito de reduzir as falhas e esquecimentos. PMID- 27556714 TI - Creation of complexity assessment tool for patients receiving home care. AB - OBJECTIVE: To create and validate a complexity assessment tool for patients receiving home care from a public health service. METHOD: A diagnostic accuracy study, with estimates for the tool's validity and reliability. Measurements of sensitivity and specificity were considered when producing validity estimates. The resulting tool was used for testing. Assessment by a specialized team of home care professionals was used as the gold standard. In the tool's reliability study, the authors used the Kappa statistic. The tool's sensitivity and specificity were analyzed using various cut-off points. RESULTS: On the best cut off point-21-with the gold standard, a sensitivity of 75.5% was obtained, with the limits of confidence interval (95%) at 68.3% and 82.8% and specificity of 53.2%, with the limits of confidence interval (95%) at 43.8% and 62.7%. CONCLUSION: The tool presented evidence of validity and reliability, possibly helping in service organization at patient admission, care type change, or support during the creation of care plans. OBJETIVO: Elaborar e validar instrumento de classificacao de complexidade assistencial de pacientes em atencao domiciliar de um servico publico de saude. METODO: Estudo de acuracia de diagnostico, com estimativas de validade e de reprodutibilidade do instrumento. Para a estimativa da validade foram consideradas as medidas de sensibilidade e especificidade; como teste, o instrumento elaborado e como padrao ouro, a classificacao atribuida por equipe especializada de profissionais de saude em atencao domiciliar. No estudo de reprodutibilidade do instrumento foi utilizada a estatistica Kappa. A sensibilidade e especificidade do instrumento foram analisadas considerando-se diferentes pontos de corte. RESULTADOS: Para o melhor ponto de corte - 21 - com o padrao ouro obteve-se Sensibilidade de 75,5% com os limites do IC (95%) iguais a 68,3% e 82,8% e Especificidade igual a 53,2% com os limites do IC (95%) iguais a 43,8% e 62,7%. CONCLUSAO: O instrumento apresentou evidencias de validade e reprodutibilidade, podendo vir a auxiliar na organizacao do servico, quer na admissao do paciente, quer na migracao de modalidade assistencial e no suporte para elaboracao do plano terapeutico. PMID- 27556713 TI - Triage in an adult emergency service: patient satisfaction. AB - OBJECTIVE: Assess the degree of patient satisfaction with triage in the adult emergency service of a public hospital. METHOD: Exploratory, descriptive, cross sectional study with a quantitative approach. Three hundred patients were interviewed and the data were analyzed using descriptive statistics based on sociodemographic variables and those related to patient satisfaction. RESULTS: There was a predominance of women, with elementary education and a mean age of 41 years. Most of the interviewees reported being satisfied in regard to the following items: timely service, embracement, trust, environment (comfort, cleanliness and signage), humanization (courtesy, respect, and interest), timely referral/scheduling of appointments and care expectations. CONCLUSION: There was a high level of patient satisfaction, evidenced by the strong association of user satisfaction with the items investigated. OBJETIVO: Avaliar o grau de satisfacao dos usuarios no setor de Acolhimento com Classificacao de Risco do Pronto-Socorro Adulto de um hospital publico. METODO: Pesquisa exploratoria, descritiva e transversal com abordagem quantitativa. Foram entrevistados 300 usuarios e os dados foram analisados por meio de estatistica descritiva a partir de variaveis sociodemograficas e as relacionadas a satisfacao do usuario. RESULTADOS: Houve predominancia do sexo feminino, nivel de escolaridade fundamental e idade media de 41 anos. A maioria dos entrevistados respondeu estar satisfeito em relacao aos itens: agilidade no atendimento; acolhimento; confianca; ambiencia (conforto, limpeza, sinalizacao), humanizacao (educacao, respeito e interesse); agilidade no encaminhamento/agendamento de consulta e expectativa sobre o servico. CONCLUSAO: Verificou-se elevado grau de satisfacao dos usuarios, evidenciada pela forte associacao da satisfacao do usuario com os itens investigados. PMID- 27556715 TI - Tool and ideological knowledge in Street Outreach Office working process. AB - OBJECTIVE: To identify ideological knowledge and tool knowledgethat provide support to the Street Outreach Office working process. METHOD: Qualitative and exploratory research. TwentyStreet Outreach Office professionals and six users collected the data, applying different semi-structured interview schedules for each category of participants. The resulting categories were analyzed in light of tool and ideological knowledge presented in the working process. RESULTS: From the participant discourses the following ideological knowledge emerged: public policies and the needs of the person ina street situation and tool knowledge, as well as devices and tools for the care of people in street situations and a weekly schedule. CONCLUSION: The focus on the working process discourse, supported by ideological knowledge, was verified. The structural dimension of the objective reality of the population in street situations was perceptible in the social determination of being situating on the street. When daily situations were revealed, the limitations to be overcome in the working process context were noticed. OBJETIVO: Identificar os saberes ideologicos e instrumentais que subsidiam o processo de trabalho do Consultorio na Rua. METODO: Pesquisa qualitativa e exploratoria. A coleta de dados foi realizada junto a 20 profissionais e seis usuarios do Consultorio na Rua de um municipio do sul do Brasil, por meio de entrevistas com roteiros semiestruturados distintos para cada categoria de participantes. As classes resultantes foram analisadas a luz dos saberes ideologicos e instrumentais presentes no processo de trabalho. RESULTADOS: Dos discursos dos participantes emergiram os saberes ideologicos: politicas publicas e necessidades da pessoa em situacao de rua e os saberes instrumentais: dispositivos e instrumentos no cuidado a pessoa em situacao de rua e agenda semanal. CONCLUSAO: Constatou-se a centralidade dos discursos no processo de trabalho, sustentado pelos saberes ideologicos. A dimensao estrutural da realidade objetiva da populacao em situacao de rua foi perceptivel na determinacao social do situar-se na rua. Ao descortinar contradicoes no cotidiano, apontam-se limites a serem superados no ambito do processo de trabalho. PMID- 27556716 TI - Partner notification for sexually transmitted infections and perception of notified partners. AB - OBJECTIVE: Learn the perceptions of patients with sexually transmitted infections and sexual partners who are notified of the infection. METHOD: A descriptive and qualitative study, based on the collective subject discourse technique, was conducted in four healthcare centers of reference in Fortaleza, Ceara, from March to July 2014. The sample comprised 21 subjects (11 index patients and 10 notified partners). RESULTS: The index patients reported complicity, concern about the partner's health and revelation of diagnosis aiming to preserve the relationship. The partners showed antagonistic perceptions: tranquility-betrayal, fear of death, of incurability and the diagnosis, especially of HIV. The reasons for coming to a healthcare center were: fear of being sick, attenuation of guilt of infection transmission, need for diagnosis, early start of treatment. CONCLUSION: Fear of losing trust, insecurities when dealing with a sexual infection and being responsible or co-responsible for the transmission were the predominant feelings. Various types of partner notification were reported (verbal, telephone, notification card), according to individual convenience. This study suggests the use of alternative methods of notification and an integrated system of notification. OBJETIVO: Conhecer as percepcoes dos pacientes com infeccoes sexualmente transmissiveis e parceiros sexuais sobre a notificacao da infeccao. METODO: Estudo descritivo e qualitativo, baseado na tecnica do discurso do sujeito coletivo, realizado em quatro Unidades de Saude de referencia em Fortaleza/CE, de marco a julho de 2014. Amostra composta por 21 sujeitos (11 pacientes-indice e 10 parceiros notificados). RESULTADOS: Pacientes-indice relataram cumplicidade, preocupacao com a saude do parceiro e revelacao do diagnostico como forma de preservacao do relacionamento. Para os parceiros, as percepcoes foram antagonicas: tranquilidade-traicao, medo da morte, da incurabilidade e do diagnostico, especialmente do HIV. Os motivos para o comparecimento foram: medo de estar doente, atenuacao da culpa relativa a transmissao, necessidade do diagnostico, inicio precoce do tratamento. CONCLUSAO: Predominou o medo da quebra da confianca, insegurancas em lidar com uma infeccao sexual e ser responsavel ou corresponsavel pela transmissao. As formas de comunicacao as parcerias sexuais foram diversificadas (verbal, telefone, cartao de comunicacao), atendendo a uma conveniencia individual. Sugere-se a uniao de metodos alternativos de notificacao e um sistema de notificacao integrado. PMID- 27556717 TI - CLINICAL SIGNS AND SYMPTOMS OF SEXUALLY TRANSMITTED INFECTIONS COMMUNICATED IN LIBRAS. AB - OBJECTIVE: To validate a video containing image representations of clinical signs and symptoms of sexually transmitted infections expressed in Libras. METHOD: Methodology development study conducted in an audio communication school. Thirty six deaf people were selected. A video containing image representations of clinical signs and symptoms of sexually transmitted infections expressed in Libras was produced. Semantic validation was performed by deaf students and content validation by three judges who are Libras experts. The validation results were subjected to the Content Validity Index, where an index score > 0.80/80% was considered as agreement among judges. RESULTS: Seven signs and symptoms related to sexually transmitted infections were validated and obtained satisfactory Content Validity Indexes, most of them with 100% representativeness and agreement. CONCLUSION: The validation process made the expressions of signs and symptoms related to sexually transmitted infections represented in Libras valid for establishing effective communication in the area of the study, turning it into a care tool that facilitates and standardizes communication with deaf people through Libras. OBJETIVO: Validar um video contendo as representacoes imageticas de sinais e sintomas clinicos de infeccoes sexualmente transmissiveis expressas em Libras. METODO: Estudo de desenvolvimento metodologico, realizado em uma escola de audiocomunicacao. Selecionou-se uma amostra de 36 surdos. Elaborou-se um video contendo a representacao imagetica de sinais e sintomas de infeccoes sexualmente transmissiveis expressos em Libras. A validacao semantica foi realizada pelos surdos e a validacao de conteudo por tres juizes experts em Libras. Os resultados da validacao foram submetidos ao Indice de Validade de Conteudo, considerando-se o escore do indice > 0,80/80% de concordancia entre os juizes. RESULTADOS: Foram validados sete sinais e sintomas relacionados as infeccoes sexualmente transmissiveis que obtiveram Indices de Validade de Conteudos satisfatorios e em sua maioria com 100% de representatividade e concordancia. CONCLUSAO: O processo de validacao tornou validas as expressoes de sinais e sintomas relacionados as infeccoes sexualmente transmissiveis representadas em Libras para estabelecer, na regiao do estudo, uma comunicacao eficiente, tornando-se uma ferramenta assistiva que permite facilidade e uniformidade na comunicacao com os surdos por meio da Libras. PMID- 27556718 TI - Quotidian of accompanying family members in an environment of care: the emergence of hospital tribes. AB - OBJETIVO: Compreender o relacionamento no quotidiano dos familiares acompanhantes nos cenarios de cuidado que se aproximam da metafora da tribo no ambiente hospitalar. METODO: Estudo qualitativo com dados coletados a partir de entrevistas semiestruturadas e observacao com 16 familiares acompanhantes de pessoas hospitalizadas com dependencia para o autocuidado. Os dados foram submetidos a analise tematica e analisados atraves da metafora da tribo proposta pela sociologia compreensiva. RESULTADOS: Os familiares formam um agrupamento social em torno do cuidado onde encontramos as caracteristicas das tribos: a ambiencia emocional; a solidariedade baseada nos vinculos de simpatia e ajuda mutua; a nebulosa afetual no processo interacional; a logica da fusao nas relacoes tacteis e a comunhao/religiosidade no processo de ligacao numa identidade coletiva. CONCLUSAO: Os familiares na presenca do tragico criam agrupamentos sociais que se assemelham a tribos cujo totem e o cuidado. OBJECTIVE: Understand the quotidian relationships of accompanying family members in an environment of care, which are close to the metaphor of a tribe in hospital environment. METHODQualitative study with data gathered from semi-structured interviews and observations with 16 family members accompanying hospitalized individuals with dependence on self-care. Data were submitted to thematic analysis, and analyzed through the metaphor of "tribe" proposed by comprehensive sociology. RESULTS: Family members build up social clusters around caring, where we find traits typical of tribes: emotional ambience; solidarity based on links of sympathy and mutual assistance; an affectual nebula in the process of interaction; a logic of fusion in tactile relations; and communion/religiosity in the process of connecting in a collective identity. CONCLUSION: In the presence of tragedy, families build social clusters similar to tribes having care as a totem. PMID- 27556719 TI - Nurses in post-operative heart surgery: professional competencies and organization strategies. AB - OBJECTIVE: To analyze nurses' competencies with regard to their work in post operative heart surgery and the strategies implemented to mobilize these competencies. METHOD: This was an exploratory study with a qualitative approach and a methodological design of collective case study. It was carried out in three post-operative heart surgery units, consisting of 18 nurses. Direct observation and semi-structured interviews were employed to collect data. Data were construed through thematic analysis. RESULTS: nine competencies were found, as follows: theoretical-practical knowledge; high-complexity nursing care; nursing supervision; leadership in nursing; decision making; conflict management; personnel management; material and financial resources management; and on-job continued education. Organizational and individual strategies were employed to develop and improve competencies such as regular offerings of courses and lectures, in addition to the individual pursuit for knowledge and improvement. CONCLUSION: the study is expected to lead future nurses and training centers to evaluate the need for furthur training required to work in cardiac units, and also the need for implementing programs aimed at developing the competencies of these professionals. OBJETIVO: Analisar as competencias dos enfermeiros para atuarem no pos-operatorio de cirurgia cardiaca e estrategias implementadas para a mobilizacao dessas competencias. METODO: Estudo exploratorio, com abordagem qualitativa e desenho metodologico estudo de caso coletivo. Foi realizado em tres unidades pos-operatorias de cirurgias cardiacas, com 18 enfermeiros. Na coleta de dados utilizou-se observacao direta e entrevista semiestruturada. Para interpretacao dos dados optou-se pela analise tematica. RESULTADOS: Foram identificadas nove competencias, sendo: conhecimento teorico-pratico, cuidados de enfermagem de alta complexidade, supervisao e lideranca em enfermagem, tomada de decisao, gerenciamento de conflitos, de recursos humanos, materiais, financeiros e educacao continuada em servico. Estrategias organizacionais e individuais sao realizadas a fim de desenvolver e aprimorar competencias, tais como: oferecimento de cursos e palestras periodicamente, alem da busca individual por conhecimento e aperfeicoamento. CONCLUSAO: O estudo deve provocar a reflexao de futuros enfermeiros e dos centros formadores quanto a formacao necessaria para atuar em unidades cardiacas e sobre a necessidade de implementacao de programas que visam desenvolver competencias nestes profissionais. PMID- 27556720 TI - Teamwork in a coronary care unit: facilitating and hindering aspects. AB - OBJECTIVE: To identify, within a multidisciplinary team, the facilitating and hindering aspects for teamwork in a coronary care unit. METHOD: A descriptive study, with qualitative and quantitative data, was carried out in the coronary care unit of a public hospital. The study population consisted of professionals working in the unit for at least one year. Those who were on leave or who were not located were excluded. The critical incident technique was used for data collection, by means of semi-structured interviews. For data analysis, content analysis and the critical incident technique were applied. RESULTS: Participants were 45 professionals: 29 nursing professionals; 11 physicians; 4 physical therapists; and 1 psychologist. A total of 49 situations (77.6% with negative references); 385 behaviors (54.2% with positive references); and 182 consequences emerged (71.9% with negative references). Positive references facilitate teamwork, whereas negative references hinder it. A collaborative/communicative interprofessional relationship was evidenced as a facilitator; whereas poor collaboration among agents/inadequate management was a hindering aspect. CONCLUSION: Despite the prevalence of negative situations and consequences, the emphasis on positive behaviors reveals the efforts the agents make in order to overcome obstacles and carry out teamwork. OBJETIVO: Identificar, junto a equipe multiprofissional, aspectos facilitadores e dificultadores do trabalho em equipe em Unidade Coronariana. METODO: Estudo descritivo, com dados qualitativos e quantitativos, realizado em Unidade Coronariana/Hospital publico. Populacao constituida de profissionais atuantes na Unidade ha, pelo menos, um ano. Excluidos os afastados do trabalho e os que nao foram nao localizados. Para a coleta de informacoes, utilizou-se da Tecnica do Incidente Critico por meio de entrevista semiestruturada. Para a analise dos dados, utilizaram-se da Analise de Conteudo e Tecnica do Incidente Critico. RESULTADOS: Participaram 45 profissionais: 29 profissionais de enfermagem; 11 medicos; quatro fisioterapeutas e um psicologo. Emergiram 49 situacoes (77,6% com referencias negativas); 385 comportamentos (54,2% com referencias positivas); e 182 consequencias (71,9% com referencias negativas). Referencias positivas facilitam o trabalho em equipe, e as negativas o dificultam. Relacionamento interprofissional colaborativo/comunicativo foi evidenciado como facilitador; baixa colaboracao entre agentes/gerenciamento inadequado como dificultador. CONCLUSAO: Apesar de predominarem situacoes e consequencias negativas, enfase em comportamentos positivos revela esforco dos agentes para vencer obstaculos e realizar trabalho em equipe. PMID- 27556721 TI - Patient safety in organizational culture as perceived by leaderships of hospital institutions with different types of administration. AB - OBJECTIVE: To identify the perceptions of leaderships toward patient safety culture dimensions in the routine of hospitals with different administrative profiles: government, social and private organizations, and make correlations among participating institutions regarding dimensions of patient safety culture used. METHOD: A quantitative cross-sectional study that used the Self Assessment Questionnaire 30 translated into Portuguese. The data were processed by analysis of variance (ANOVA) in addition to descriptive statistics, with statistical significance set at p-value <= 0.05. RESULTS: According to the participants' perceptions, the significant dimensions of patient safety culture were 'patient safety climate' and 'organizational learning', with 81% explanatory power. Mean scores showed that among private organizations, higher values were attributed to statements; however, the correlation between dimensions was stronger among government hospitals. CONCLUSION: Different hospital organizations present distinct values for each dimension of patient safety culture and their investigation enables professionals to identify which dimensions need to be introduced or improved to increase patient safety. OBJETIVO: Identificar percepcoes das liderancas sobre as dimensoes da cultura de seguranca do paciente no cotidiano de hospitais de diferentes perfis administrativos: publicos, organizacoes sociais e privados, e realizar correlacao entre as instituicoes participantes, de acordo com as dimensoes da cultura de seguranca do paciente utilizadas. METODO: Estudo transversal de aspecto quantitativo obtido por meio da aplicacao do instrumento Self Assessment Questionnaire 30, traduzido para a lingua portuguesa. Os dados foram tratados com analise de variancia (ANOVA), alem das estatisticas descritivas, considerando como de significancia estatistica valores de p-valor <= 0,05. RESULTADOS: Segundo a percepcao dos participantes do estudo, as dimensoes significativas para a cultura de seguranca do paciente foram Ambiente de Seguranca do Paciente e Aprendizado Organizacional, com poder explicativo de 81%. A media de respostas obtidas evidenciou que nas organizacoes privadas houve maiores valores atribuidos as questoes, porem a correlacao entre as dimensoes foi mais forte nas organizacoes publicas. CONCLUSAO: As dimensoes da cultura de seguranca do paciente tem valores distintos nas diferentes organizacoes hospitalares e a sua investigacao possibilita identificar quais necessitam ser introduzidas ou aprimoradas para maior seguranca do paciente. PMID- 27556722 TI - Portuguese nursing: history of the life and activism of Maria Augusta Sousa. AB - OBJECTIVE: To analyze the history of the life and activism of Portuguese nurse Maria Augusta Sousa. METHOD: Sousa's life story was obtained by means of semi structured interview swith Sousa as the oral source of data. NVivo qualitative research software was used for data analysis. Content analysis focused on thematic analysis based on the theoretical and philosophical ideas of Michel Foucault, in particular, power and techniques of the self. RESULTS: Alienation and political participation were revealed as pertinent issues. In techniques of production of activist subjects, the following were highlighted: the importance of the review of formal education; actions of involvement with the world, society and the profession; and finally, techniques of the self, techniques of constitution of activist subjects, professional identity and way of being. CONCLUSION: The constitution of the nurse Maria Augusta Sousa as an activist came about through questioning of how to be, education in the context of her family, and political engagement in Catholic Youth. This impacted her trajectory of contributions to Portuguese nursing, as expressed in the following achievements: the integration of nursing training into higher education; the creation of the Regulation of Nurses Professional Practice; and implementation of the Order of Nurses. OBJETIVO: Analisar a historia de vida e militancia da enfermeira Maria Augusta Sousa. METODO: Historia de vida, tendo como fonte oral a entrevista semiestruturada. Na analise de dados utilizou-se do software de pesquisa qualitativa Nvivo, e a analise de conteudo com foco na analise tematica e com base teorico-filosofica de Michel Foucault, em especial, o poder e as tecnicas de si. RESULTADOS: Evidenciaram-se a alienacao e a participacao politica comoquestoes pertinentes. Nas tecnicas de producao de sujeitos militantes destacam-se a importanciada revisao da educacao formal, dos atos de implicacao com o mundo, a sociedade e a profissao, e por fim, as tecnicas de si, tecnicas de constituicao de sujeitos militantes, a identidade profissional e o modo de ser. CONCLUSAO: A constituicao da enfermeira Maria Augusta Sousa como militante acontece por questoes do modo de ser, da educacao familiar e do seu engajamento politico na Juventude Catolica, que repercutiu em uma trajetoria de contribuicao para enfermagem portuguesa, expressa nas seguintes conquistas: a integracao do Ensino de Enfermagem no Ensino Superior, a criacao do Regulamento do Exercicio Profissional de Enfermagem e a implantacao da Ordem dos Enfermeiros. PMID- 27556723 TI - Policies for control and prevention of infections related to healthcare assistance in Brazil: a conceptual analysis. AB - This article is a theoretical-reflexive study that aims to discuss the development and changes in the quality of healthcare assistance to the patient over the years in Brazil, in light of the policies of control and prevention of Healthcare-associated Infection (HAI). Aspects of HAI and the process of change in health policy in Brazil, as well as the quality of assistance associated with its control, are approached in relation to policies of patient safety. There are various new theoretical and practical proposals created in Brazil. In spite of the difficulty of measuring patient safety, directed to the prevention and control of HAI, we emphasize that to only create policies and establish norms, guidelines, and indicators is not sufficient. If no structural support or conditions exist for interventions in the practices of healthcare professionals, aiming at results in acceptable levels, the control of HAI will not be achieved. Resumo Trata-se um estudo teorico-reflexivo, que objetiva discutir a evolucao e as mudancas na qualidade da assistencia ao paciente, ao longo dos anos no Brasil, a luz das politicas de controle e prevencao da Infeccao Relacionada a Assistencia a Saude (IRAS). Aspectos sobre IRAS e o processo de mudanca nas politicas de saude no Brasil, bem como a qualidade da assistencia associada ao seu controle, sao abordados em relacao as politicas de seguranca do paciente. Ha novas e varias propostas teoricas e praticas criadas no Brasil. Apesar da dificuldade de medir a seguranca do paciente, direcionada a prevencao e controle das IRAS, enfatiza-se que somente criar politicas, estabelecer normas, diretrizes e indicadores nao sao suficientes. Se nao houver suporte de estrutura e condicoes para as intervencoes nas praticas dos profissionais na assistencia prestada ao paciente, visando resultados em niveis aceitaveis, o controle das IRAS nao sera alcancado. PMID- 27556724 TI - The experiences of pregnant women at an advanced maternal age: an integrative review. AB - OBJECTIVE: To identify in the literature how the experiences of women age 35 or above are described in terms of pregnancy. METHOD: Integrative review based on MEDLINE/PubMed, CINAHL, LILACS, and SciELO databases, with no time period constraint. RESULTS: Eighteen studies that dealt with the experiences of pregnant women at an advanced maternal age were selected and analyzed. The studies evidenced four theme categories: the search for information, which pointed to a deficit of information supplied by health care professionals; perceiving the risks, which pointed to women's concerns about their own health and their children's; the ideal moment for motherhood, with different reasons for postponing it; and adjusting to a new routine, showing a concern regarding changes in daily life. CONCLUSION: From the results, it was possible to understand that other factors, in addition to those that include risks, are present in the experiences of older pregnant women and point to a need to involve such aspects in nursing care to create comprehensive strategies that are aligned with these women's needs. OBJETIVO: Identificar na literatura como sao descritas as experiencias das mulheres com idade igual ou superior a 35 anos na gestacao. METODO: Revisao integrativa realizada nas bases de dados MEDLINE/PubMed, CINAHL, LILACS e SciELO, sem restricao de periodo. RESULTADOS: Foram selecionados e analisados 18 estudos que tratavam das experiencias das mulheres na gestacao em idade avancada. Os estudos evidenciaram quatro categorias tematicas: A busca por informacoes, que mostrou aspectos como deficit de informacoes fornecidas pelos profissionais da saude;Percebendo os riscos, que apontou uma preocupacao da mulher com a propria saude e a do filho;Momento ideal para a maternidade, com diferentes motivos para o adiamento; e Adaptacao a nova rotina, com a preocupacao em relacao as mudancas no cotidiano. CONCLUSAO: A partir dos resultados, foi possivel compreender que outros fatores, alem dos que incluem os riscos, permeiam as experiencias da mulher na gestacao em idade avancada e induzem a necessidade de envolver tais aspectos no cuidado de enfermagem para construir estrategias abrangentes e condizentes com as necessidades dessas mulheres. PMID- 27556725 TI - Hyaluronic acid covers in burn treatment: a systematic review. AB - OBJECTIVE: To evaluate the effectiveness of hyaluronic acid in the healing of partial thickness burns. METHOD: Systematic review of randomized controlled trials on the use of hyaluronic acid for the topical treatment of skin burns, based on recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Two randomized controlled trials that analyzed 143 patients with partial thickness burns and/or deep partial thickness burns were selected. They compared the application of hyaluronic acid 0.2% associated to silver sulfadiazine 1% 5g/cm2 versus silver sulfadiazine 1% 5g/cm2 alone for the outcome of complete healing. CONCLUSION: This review emphasizes the need for new well-designed randomized controlled trials to establish the therapeutic relevance of hyaluronic acid with respect to the healing of burns of partial thickness or deep partial thickness. OBJETIVO: Avaliar a efetividade do acido hialuronico na cicatrizacao de queimaduras de espessura parcial. METODO: Revisao sistematica de ensaios clinicos randomizados sobre a utilizacao de acido hialuronico no tratamento topico de queimaduras de pele, baseada nas recomendacoes do Cochrane Handbook for Systematic Reviews of Interventions. RESULTADOS: Foram recuperados dois ensaios clinicos randomizados que analisaram 143 pacientes portadores de queimaduras de espessura parcial e/ou espessura parcial profunda, comparando a aplicacao de Acido Hialuronico 0,2% associado a Sulfadiazina de Prata 1% 5g/cm2, versus Sulfadiazina de Prata 1% 5g/cm2 isolada, para o desfecho cicatrizacao completa. CONCLUSAO: Esta revisao enfatiza a necessidade de novos ensaios clinicos randomizados bem delineados para estabelecimento da relevancia terapeutica do acido hialuronico no que tange a cicatrizacao de queimaduras de espessura parcial ou espessura parcial profunda. PMID- 27556726 TI - Comparison study between multicontrast atherosclerosis characterization (MATCH) and conventional multicontrast MRI of carotid plaque with histology validation. AB - PURPOSE: To compare Multicontrast ATherosclerosis Characterization (MATCH) with conventional multicontrast magnetic resonance imaging (MRI) in the characterization and quantification of carotid plaque components. MATERIALS AND METHODS: Fifty-three consecutive patients underwent carotid plaque 3.0T MRI including conventional multicontrast sequences and MATCH, with 13 of them having carotid endarterectomy for histology validation. The detection of major plaque components including lipid-rich necrotic core (LRNC), loose matrix (LM), intraplaque hemorrhage (IPH), and calcification (CA) and measurement of lumen area, outer wall area, normalized wall index (NWI), and plaque components areas were compared between the two protocols. RESULTS: Plaque analysis and comparison were done on 298 matched cross-sectional MRI. MATCH detected significantly more calcifications than conventional consequences (P < 0.01). The difference in detection of IPH (P = 0.07) and LRNC (P = 0.10) approached significance. There was no significant difference in demonstration of LM (P =0.52). A larger area of IPH and CA was measured on MATCH (P < 0.01). The difference nearly reached significance between the two protocols in measuring lumen area (P = 0.09) and outer wall area (P = 0.08). No significant difference was found when measuring the mean area of LRNC (P = 0.15) and LM (P = 0.14) and NWI (P = 0.38). By using receiver operating characteristic curve (ROC) analysis, the accuracy of MATCH and conventional protocols did not differ significantly in the detection of IPH (P = 0.15), LRNC (P = 0.61), LM (P = 0.48), and CA (P = 0.11) when histology served as a reference. CONCLUSION: MATCH was comparable if not superior to conventional protocol in identification and quantification of major carotid plaque components. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:764-770. PMID- 27556727 TI - The influence of maternal care and overprotection on youth adrenocortical stress response: a multiphase growth curve analysis. AB - We examined the association between two dimensions of maternal parenting style (care and overprotection) and cortisol response to an acute laboratory-induced stressor in healthy youth. Forty-three participants completed the Parental Bonding Instrument and an adapted version of the Trier Social Stress Test-Child (TSST-C). Nine cortisol samples were collected to investigate heterogeneity in different phases of youth's stress response. Multiphase growth-curve modeling was utilized to create latent factors corresponding to individual differences in cortisol during baseline, reactivity, and recovery to the TSST-C. Youth report of maternal overprotection was associated with lower baseline cortisol levels, and a slower cortisol decline during recovery, controlling for maternal care, puberty, and gender. No additive or interactive effects involving maternal care emerged. These findings suggest that maternal overprotection may exert a unique and important influence on youth's stress response. PMID- 27556728 TI - Pathophysiology of peripheral arterial disease in diabetes mellitus. AB - Peripheral arterial disease (PAD) increases the risk of lower extremity amputation. It is also an independent predictor of cardiovascular and cerebrovascular ischemic events, affecting both the quality and expectancy of life. Many studies have demonstrated that the prevalence of PAD in patients with diabetes mellitus (DM) is higher than in non-diabetic patients. In diabetic patients, PAD occurs early with rapid progression, and is frequently asymptomatic. Multiple metabolic aberrations in DM, such as advanced glycation end-products, low-density lipoprotein cholesterol, and abnormal oxidative stress, have been shown to worsen PAD. However, the role of DM in PAD is not completely understood. The purpose of the present article is to review and discuss the pathophysiology of PAD in DM. PMID- 27556729 TI - First Total Synthesis, Structure Revision, and Natural History of the Smallest Cytochalasin: (+)-Periconiasin G. AB - The total synthesis of the smallest cytochalasin isolated so far, periconiasin G, which bears a seven-membered ring in lieu of the usual macrocycle, has been performed from both enantiomers of citronellal, relying on an intramolecular Diels-Alder reaction in favor of the natural endo stereochemistry. We show that, among the four synthesized stereoisomers, including the exo isomers, the one matching the NMR data of the natural product was not that assigned in the original report, imposing structure revision. The natural product, previously isolated from a plant-mutualistic fungus, was biologically investigated taking into account its natural history, showing significant effects against the phytopathogenic fungus Botrytis cinerea and thus opening new opportunities in combating this pest. PMID- 27556730 TI - Affective bias in visual working memory is associated with capacity. AB - How does the affective nature of task stimuli modulate working memory (WM)? This study investigates whether WM maintains emotional information in a biased manner to meet the motivational principle of approaching positivity and avoiding negativity by retaining more approach-related positive content over avoidance related negative content. This bias may exist regardless of individual differences in WM functionality, as indexed by WM capacity (overall bias hypothesis). Alternatively, this bias may be contingent on WM capacity (capacity based hypothesis), in which a better WM system may be more likely to reveal an adaptive bias. In two experiments, participants performed change localisation tasks with emotional and non-emotional stimuli to estimate the number of items that they could retain for each of those stimuli. Although participants did not seem to remember one type of emotional content (e.g. happy faces) better than the other type of emotional content (e.g. sad faces), there was a significant correlation between WM capacity and affective bias. Specifically, participants with higher WM capacity for non-emotional stimuli (colours or line-drawing symbols) tended to maintain more happy faces over sad faces. These findings demonstrated the presence of a "built-in" affective bias in WM as a function of its systematic limitations, favouring the capacity-based hypothesis. PMID- 27556731 TI - Comprehensive attenuation of IL-25-induced airway hyperresponsiveness, inflammation and remodelling by the PI3K inhibitor LY294002. AB - BACKGROUND AND OBJECTIVE: Existing in vitro and in vivo studies suggest that both IL-25 and phosphoinositide 3-kinases (PI3Ks) exhibit broad effects on the functions of immune cells implicated in the pathogenesis of asthma. Whether the blockade of PI3K signalling directly inhibits the asthma relevant pathogenetic changes induced by IL-25 in an in vivo condition is still unclear. Using an established IL-25-induced murine model of asthma, we undertook a comprehensive evaluation of the effects of co-administered LY294002, a pharmacological pan inhibitor of PI3K on IL-25-induced changes on this model, with particular regard to airway remodelling. METHODS: BALB/c mice were serially intranasally challenged with IL-25 according to an established protocol to induce airway inflammation, hyperresponsiveness (AHR) and remodelling. In an additional subgroup LY294002 was administered intranasally. Lung function and airway cytokine and chemokine concentrations and cellular infiltration and remodelling changes assessed by histology and immunohistochemistry were measured at specific time points. RESULTS: Intranasal administration of LY294002 significantly inhibited IL-25 induced AHR and recruitment of inflammatory cells into bronchoalveolar lavage fluid. LY294002 also attenuated IL-25-induced increased concentrations of cytokines and chemokines in lung tissue. Histological and immunohistochemical analysis showed that LY294002 also significantly inhibited IL-25-induced lung tissue eosinophilia, mucus production, collagen deposition, smooth muscle hypertrophy and angiogenesis. CONCLUSION: The PI3K pan-inhibitor LY294002 attenuated not only IL-25-induced asthma-like AHR and airway inflammation but also remodelling in this model, suggesting that PI3K is a major downstream messenger for IL-25 and that targeting this pathway might reduce asthma symptoms in the short term and airway remodelling in the longer term. PMID- 27556732 TI - Microfiltration of enzyme treated egg whites for accelerated detection of viable Salmonella. AB - We report detection of <13 CFU of Salmonella per 25 g egg white within 7 h by concentrating the bacteria using microfiltration through 0.2-MUm cutoff polyethersulfone hollow fiber membranes. A combination of enzyme treatment, controlled cross-flow on both sides of the hollow fibers, and media selection were key to controlling membrane fouling so that rapid concentration and the subsequent detection of low numbers of microbial cells were achieved. We leveraged the protective effect of egg white proteins and peptone so that the proteolytic enzymes did not attack the living cells while hydrolyzing the egg white proteins responsible for fouling. The molecular weight of egg white proteins was reduced from about 70 kDa to 15 kDa during hydrolysis. This enabled a 50-fold concentration of the cells when a volume of 525 mL of peptone and egg white, containing 13 CFU of Salmonella, was decreased to a 10 mL volume in 50 min. A 10-min microcentrifugation step further concentrated the viable Salmonella cells by 10*. The final cell recovery exceeded 100%, indicating that microbial growth occurred during the 3-h processing time. The experiments leading to rapid concentration, recovery, and detection provided further insights on the nature of membrane fouling enabling fouling effects to be mitigated. Unlike most membrane processes where protein recovery is the goal, recovery of viable microorganisms for pathogen detection is the key measure of success, with modification of cell free proteins being both acceptable and required to achieve rapid microfiltration of viable microorganisms. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1464-1471, 2016. PMID- 27556733 TI - Mechanisms for allosteric activation of protease DegS by ligand binding and oligomerization as revealed from molecular dynamics simulations. AB - A local perturbation of a protein may lead to functional changes at some distal site, a phenomenon denoted as allostery. Here, we study the allosteric control of a protease using molecular dynamics simulations. The system considered is the bacterial protein DegS which includes a protease domain activated on ligand binding to an adjacent PDZ domain. Starting from crystallographic structures of DegS homo-trimers, we perform simulations of the ligand-free and -bound state of DegS at equilibrium. Considering a single protomer only, the trimeric state was mimicked by applying restraints on the residues in contact with other protomers in the DegS trimer. In addition, the bound state was also simulated without any restraints to mimic the monomer. Our results suggest that not only ligand release but also disassembly of a DegS trimer inhibits proteolytic activity. Considering various observables for structural changes, we infer allosteric pathways from the interface with other protomers to the active site. Moreover, we study how ligand release leads to (i) catalytically relevant changes involving residues 199-201 and (ii) a transition from a stretched to a bent conformation for residues 217 219 (which prohibits proper substrate binding). Finally, based on ligand-induced Calpha shifts we identify residues in contact with other protomers in the DegS trimer that likely transduce the perturbation from ligand release from a given protomer to adjacent protomers. These residues likely play a key role in the experimentally known effect of ligand release from a protomer on the proteolytic activity of the other protomers. Proteins 2016; 84:1690-1705. (c) 2016 Wiley Periodicals, Inc. PMID- 27556734 TI - IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function. AB - Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis. However, the molecular mechanisms involved in IL31-driven pathological remodeling in skin diseases remain largely unknown. Here, we studied the role of IL-31 in skin damage as a result of intradermal administration of recombinant IL-31 into mice. Notably, IL-31 was sufficient to increase epidermal basal-cell proliferation and thickening of the epidermal skin layer. Our findings demonstrate a progressive increase in transepidermal water loss with chronic administration of IL-31 into the skin. Further, analysis of the skin transcriptome indicates a significant increase in the transcripts involved in epidermal-cell proliferation, epidermal thickening, and mechanical integrity. In summary, our findings demonstrate an important role for IL-31 signaling in epidermal cell proliferation and thickening that together may lead to impaired skin-barrier function in pathological remodeling of the skin. PMID- 27556735 TI - Modeling Late-Summer Distribution of Golden Eagles (Aquila chrysaetos) in the Western United States. AB - Increasing development across the western United States (USA) elevates concerns about effects on wildlife resources; the golden eagle (Aquila chrysaetos) is of special concern in this regard. Knowledge of golden eagle abundance and distribution across the western USA must be improved to help identify and conserve areas of major importance to the species. We used distance sampling and visual mark-recapture procedures to estimate golden eagle abundance from aerial line-transect surveys conducted across four Bird Conservation Regions in the western USA between 15 August and 15 September in 2006-2010, 2012, and 2013. To assess golden eagle-habitat relationships at this scale, we modeled counts of golden eagles seen during surveys in 2006-2010, adjusted for probability of detection, and used land cover and other environmental factors as predictor variables within 20-km2 sampling units randomly selected from survey transects. We found evidence of positive relationships between intensity of use by golden eagles and elevation, solar radiation, and mean wind speed, and of negative relationships with the proportion of landscape classified as forest or as developed. The model accurately predicted habitat use observed during surveys conducted in 2012 and 2013. We used the model to construct a map predicting intensity of use by golden eagles during late summer across our ~2 million-km2 study area. The map can be used to help prioritize landscapes for conservation efforts, identify areas where mitigation efforts may be most effective, and identify regions for additional research and monitoring. In addition, our map can be used to develop region-specific (e.g., state-level) density estimates based on the latest information on golden eagle abundance from a late-summer survey and aid designation of geographic management units for the species. PMID- 27556736 TI - Differentiation of Benign From Metastatic Adrenal Masses in Patients With Renal Cell Carcinoma on Contrast-Enhanced CT. AB - OBJECTIVE: The purpose of this article was to determine whether imaging features on contrast-enhanced CT can differentiate benign from metastatic adrenal masses in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Between January 2008 and January 2014, 135 patients with untreated RCC were found to have 163 adrenal masses (102 benign and 61 metastatic) on contrast-enhanced CT including the corticomedullary phase (66 benign and 42 metastatic) or nephrographic phase (56 benign and 33 metastatic) or both. Imaging features of renal and adrenal masses were recorded, including T and N staging components of renal masses, internal texture, CT attenuation values, and attenuation differences between renal and adrenal masses. Logistic regression diagnostic models to differentiate benign from metastatic adrenal mass were constructed using independently significant imaging parameters in the respective corticomedullary and nephrographic phases (corticomedullary phase model and nephrographic phase model). Diagnostic performance of the models was evaluated by ROC analysis. RESULTS: Statistically significant variables for the models were regional lymphadenopathy, perirenal or renal sinus fat invasion (corticomedullary phase model only), adrenal mass size, CT attenuation value of adrenal mass, and absolute value of attenuation difference between renal and adrenal masses. Both models had excellent diagnostic performance; the AUC and optimal sensitivity and specificity for the diagnosis of metastasis were 0.991, 100%, and 92.4%, respectively, in the corticomedullary phase model and 0.947, 81.8%, and 96.4%, respectively, in the nephrographic phase model. CONCLUSION: Differentiation between benign and metastatic adrenal masses in patients with RCC can be achieved accurately by combining multiple imaging features on contrast-enhanced CT. PMID- 27556737 TI - New Guidelines for the Treatment of Drug-Susceptible Tuberculosis from the American Thoracic Society, Centers for Disease Control and Prevention, and the Infectious Diseases Society of America. Now Comes the Hard Part. PMID- 27556738 TI - Lack of Spatial Subdivision for the Snapper Lutjanus purpureus (Lutjanidae - Perciformes) from Southwest Atlantic Based on Multi-Locus Analyses. AB - The Caribbean snapper Lutjanus purpureus is a marine species fish commonly found associated with rocky seabeds and is widely distributed along of Western Atlantic. Data on stock delineation and stock recognition are essential for establishing conservation measures for commercially fished species. However, few studies have investigated the population genetic structure of this economically valuable species, and previous studies (based on only a portion of the mitochondrial DNA) provide an incomplete picture. The present study used a multi locus approach (12 segments of mitochondrial and nuclear DNA) to elucidate the levels of genetic diversity and genetic connectivity of L. purpureus populations and their demographic history. L. purpureus has high levels of genetic diversity, which probably implies in high effective population sizes values for the species. The data show that this species is genetically homogeneous throughout the geographic region analyzed, most likely as a result of dispersal during larval phase. Regarding demographic history, a historical population growth event occurred, likely due to sea level changes during the Pleistocene. PMID- 27556739 TI - Association of Fidaxomicin with C. difficile Spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production. AB - BACKGROUND: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production. METHODS: Prevalent UK C. difficile ribotypes (n = 10) were incubated with 200mg/L fidaxomicin, vancomycin or a non antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay. RESULTS: Fidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean = 10.1mg/L; range = 4.0-14mg/L) and faecal filtrate (mean = 17.4mg/L; 8.4 22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples. CONCLUSION: Fidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates. PMID- 27556742 TI - Tuning Magnetism of [MnSb4](9-) Cluster in Yb14MnSb11 through Chemical Substitutions on Yb Sites: Appearance and Disappearance of Spin Reorientation. AB - Single crystals of Yb14-xRExMnSb11 (0 < x < 0.6, RE = Pr, Nd, Sm, and Gd) were synthesized by Sn flux. The compounds are iso-structural with Ca14AlSb11 (I41/acd), and their compositions were determined by wavelength-dispersive spectroscopy. Yb14MnSb11 is described as a partially screened d-metal Kondo system with the isolated [MnSb4](9-) tetrahedral cluster having a d(5) + hole configuration that results in four unpaired electrons measured in the ferromagnetically ordered phase. All of the Yb atoms in Yb14MnSb11 are present as Yb(2+), and the additional RE in Yb14-xRExMnSb11 is trivalent, contributing one additional electron to the structure and altering the magnetic properties. All compounds show ferromagnetic ordering in the range of 39-52 K attributed to the [MnSb4](9-) magnetic moment. Temperature-dependent DC magnetization measurements of Yb14-xPrxMnSb11 (0.44 <= x <= 0.56) show a sharp downturn right below the ferromagnetic transition temperature. Single-crystal neutron diffraction shows that this downturn is caused by a spin reorientation of the [MnSb4](9-) magnetic moments from the ab-plane to c-axis. The spin reorientation behavior, caused by large anisotropy, is also observed for similar x values of RE = Nd but not for RE = Sm or Gd at any value of x. In Pr-, Nd-, and Sm-substituted crystals, the saturation moments are consistent with ~4 unpaired electrons attributed to [MnSb4](9-), indicating that local moments of Pr, Nd, and Sm do not contribute to the ferromagnetic order. In the case of RE = Pr, this is confirmed by neutron diffraction. In contrast, the magnetic measurements of RE = Gd show that the moments of Gd ferromagnetically order with the moments of [MnSb4](9-), and reduced screening of moments on Mn(2+) is evident. The sensitive variation of magnetic behavior is attributed to the various RE substitutions resulting in different interactions of the 4f-orbitals with the 3d-orbitals of Mn in the [MnSb4](9-) cluster conducted through 5p-orbitals of Sb. PMID- 27556741 TI - Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis. AB - Importance: The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. Objectives: To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. Design, Setting, and Participants: Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. Main Outcome and Measures: Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5 year follow-up. Results: One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). Conclusions and Relevance: An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging. PMID- 27556743 TI - Atmospheric Chemistry of Tetrahydrofuran, 2-Methyltetrahydrofuran, and 2,5 Dimethyltetrahydrofuran: Kinetics of Reactions with Chlorine Atoms, OD Radicals, and Ozone. AB - FTIR smog chamber techniques were used to study the kinetics of the gas-phase reactions of Cl atoms, OD radicals, and O3 with the five-membered ring-structured compounds tetrahydrofuran (C4H8O, THF), 2-methyltetrahydrofuran (CH3C4H7O, 2 MTHF), 2,5-dimethyltetrahydrofuran ((CH3)2C4H5O, 2,5-DMTHF), and furan (C4H4O). The rate coefficients determined using relative rate methods were kTHF+Cl = (1.96 +/- 0.24) * 10(-10), kTHF+OD = (1.81 +/- 0.27) * 10(-11), kTHF+O3 = (6.41 +/- 2.90) * 10(-21), k2-MTHF+Cl = (2.65 +/- 0.43) * 10(-10), k2-MTHF+OD = (2.41 +/- 0.51) * 10(-11), k2-MTHF+O3 = (1.87 +/- 0.82) * 10(-20), k2,5-DMTHF+OD = (4.56 +/ 0.68) * 10(-11), k2,5-DMTHF+Cl = (2.84 +/- 0.34) * 10(-10), k2,5-DMTHF+O3 = (4.58 +/- 2.18), kfuran+Cl = (2.39 +/- 0.27) * 10(-10), and kfuran+O3 = (2.60 +/- 0.31) * 10(-18) molecules cm(-3) s(-1). Rate coefficients of the reactions with ozone were also determined using the absolute rate method under pseudo-first order conditions. OD radicals, in place of OH radicals, were produced from CD3ONO to avoid spectral overlap of isopropyl and methyl nitrite with the reactants. The kinetics of OD radical reactions are expected to resemble the kinetics of OH radical reactions, and the rate coefficients of the reactions with OD radicals were used to calculate the atmospheric lifetimes with respect to reactions with OH radicals. The lifetimes of THF, 2-MTHF, and 2,5-DMTHF are approximately 15, 12, and 6 h, respectively. PMID- 27556740 TI - SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5). AB - Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development. PMID- 27556744 TI - Reticular Synthesis of a Series of HKUST-like MOFs with Carbon Dioxide Capture and Separation. AB - We reported a series of HKUST-like MOFs based on multiple copper-containing secondary building units (SBUs). Compound 1 is constructed by two SBUs: Cu2(CO2)4 paddle-wheel SBUs and Cu2I2 dimer SBUs. Compound 2 has Cu2(CO2)4 paddle-wheel SBUs and Cu4I4 SBUs. Furthermore, compound 3 possesses Cu2(CO2)4 paddle-wheel SBUs, Cu2I2 dimer SBUs, and Cu(CO2)4 SBUs. These compounds are promising materials for CO2 capture and separation, because they all display commendable adsorption of CO2 and high selectivity for CO2 over CH4 and N2. It is worthy to note that compound 1 exhibits the highest Brunauer-Emmett-Teller surface area (ca. 901 m(2) g(-1)) among the MOF materials based on CuxIy SBUs. In addition, compound 3 is the first case that three copper SBUs coexist in MOFs. PMID- 27556745 TI - Effect of Surface Ion Conductivity of Anion Exchange Membranes on Fuel Cell Performance. AB - Anion conductivity at the surfaces of two anion-exchange membranes (AEMs), quaternized ammonium poly(arylene ether) multiblock copolymer (QPE-bl-3) and quaternized ammonium poly(arylene perfluoro-alkylene) copolymer (QPAF-1), synthesized by our group was investigated using current-sensing atomic force microscopy under purified air at various relative humidities. The anion conducting spots were distributed inhomogeneously on the surface of QPE-bl-3, and the total areas of the anion-conducting spots and the current at each spot increased with humidity. The anion-conductive areas on QPAF-1 were found on the entire surface even at a low humidity. Distribution of the anion-conducting spots on the membrane was found to directly affect the performance of an AEM fuel cell. PMID- 27556746 TI - High Surface Area Electrodes Derived from Polymer Wrapped Carbon Nanotubes for Enhanced Energy Storage Devices. AB - Electrical double layer capacitors store energy on two adjacent layers, resulting in fast charging and discharging, but their energy density is limited by the available surface area. In this study, using poly(methyl methacrylate) assisted sonication, carbon nanotube buckypapers with specific surface area as high as 950 m(2)/g have been processed. Performance of these high surface area buckypapers have been evaluated as supercapacitor electrodes. The energy density of these high surface area electrodes at low power density of 0.68 kW/kg was 22.3 Wh/kg, and at high power density of 84 kW/kg was 3.13 Wh/kg using the ionic liquid electrolyte. PMID- 27556747 TI - Nurse-Led Titration of Angiotensin-Converting Enzyme Inhibitors, beta-Adrenergic Blocking Agents, and Angiotensin Receptor Blockers in Patients With Heart Failure With Reduced Ejection Fraction. AB - Clinical Question: Does nurse-led titration of beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with heart failure with reduced ejection fraction improve outcomes? Bottom Line: Participants whose treatment included nurse-led titration experienced fewer hospital admissions for any cause and an increase in survival, with more participants reaching target dose within a shorter period. PMID- 27556748 TI - Zika: Worse Than Thalidomide? PMID- 27556749 TI - Discussion: Advanced Technologies to Improve Wound Healing: Electrical Stimulation, Vibration Therapy, and Ultrasound-What Is the Evidence? PMID- 27556750 TI - An Update on the Appropriate Role for Hyperbaric Oxygen: Indications and Evidence. AB - BACKGROUND: Among advanced therapeutic interventions for wounds, hyperbaric oxygen therapy (HBOT) has the unique ability to ameliorate tissue hypoxia, reduce pathologic inflammation, and mitigate ischemia reperfusion injury. Most of the conditions for which it is utilized have few successful alternative treatments, and the morbidity and mortality associated with treatment failure are significant. Data on the efficacy and effectiveness of HBOT were reviewed, comparative effectiveness research of HBOT was explained, and a new paradigm for the appropriate use of HBOT was described. METHODS: Systematic reviews and randomized controlled trials that have evaluated HBOT were reviewed. RESULTS: Although numerous small randomized controlled trials provide compelling support for HBOT, the physics of the hyperbaric environment create significant barriers to trial design. The electronic health record infrastructure created to satisfy mandatory quality and registry reporting requirements as part of healthcare reform can be harnessed to facilitate the acquisition of real world data for HBOT comparative effectiveness studies and clinical decision support. CONCLUSIONS: Predictive models can identify patients unlikely to heal spontaneously and most likely to benefit from HBOT. Although electronic health records can automate the calculation of predictive models making them available at the point of care, using them in clinical decision making is complicated. It is not clear whether stakeholders will support the allocation of healthcare resources using mathematical models, but the current patient selection process mandates a 30-day delay for all patients who might benefit and allows treatment for at least some patients who cannot benefit. PMID- 27556751 TI - Discussion: An Update on the Appropriate Role for Hyperbaric Oxygen: Indications and Evidence. PMID- 27556753 TI - Negative-Pressure Wound Therapy: A Comprehensive Review of the Evidence. AB - BACKGROUND: Negative-pressure wound therapy (NPWT) and its variations are an established adjunctive modality for the treatment of wounds. Since its introduction, there have been an increasing number of publications with periods of rapid increases in the number of publications after innovations to the technology. Its application in different wound types and varying clinical scenarios has also contributed to the growing number of publications. METHODS: A comprehensive literature review (1998-2016) was performed using key words most relevant to NPWT using PubMed/Medline and OVID. Eligibility criteria included higher level evidence studies. RESULTS: One thousand three hundred and forty seven publications were identified. A total of 26 publications are included in this review: 16 comparing NPWT with standard wound dressing, 6 comparing variations of NPWT, and 4 for NPWT with instillation. The level of evidence, wound type studied, reported outcomes and impact, and key findings are tabulated and discussed. CONCLUSIONS: The number of publications has grown significantly since the inception of NPWT. In part, this reflects the variations of NPWT that have developed. However, a greater number of robust, randomized, prospective studies are needed to support its wide spread use. PMID- 27556752 TI - Cutaneous Imaging Technologies in Acute Burn and Chronic Wound Care. AB - BACKGROUND: Wound assessment relies on visual evaluation by physicians. Such assessment is largely subjective and presents the opportunity to explore the use of emergent technologies. METHODS: Emergent and powerful noninvasive imaging technologies applicable to assess burn and chronic wounds are reviewed. RESULTS: The need to estimate wound depth is critical in both chronic wound and burn injury settings. Harmonic ultrasound technology is powerful to study wound depth. It addresses the limitations of optical imaging with limited depth of penetration. What if a wound appears epithelialized by visual inspection, which shows no discharge yet is covered by repaired skin that lacks barrier function? In this case although the wound is closed as defined by current standards, it remains functionally open, presenting the risk of infection and other postclosure complications. Thus, assessment of skin barrier function is valuable in the context of assessing wound closure. Options for the study of tissue vascularization are many. If noncontact and noninvasive criteria are of importance, laser speckle imaging is powerful. Fluorescence imaging is standard in several clinical settings and is likely to serve the wound clinics well as long as indocyanine green injection is not of concern. A major advantage of harmonic ultrasound imaging of wound depth is that the same system is capable of providing information on blood flow dynamics in arterial perforators. CONCLUSION: With many productive imaging platforms to choose from, wound care is about to be transformed by technology that would help assess wound severity. PMID- 27556754 TI - A Review of Cellular and Acellular Matrix Products: Indications, Techniques, and Outcomes. AB - BACKGROUND: Wound healing is a dynamic process whereby cells, growth factors (GFs), and the extracellular matrix (ECM) interact to restore the architecture of damaged tissue. Chronic wounds can be difficult to treat due to the increased presence of inflammatory cells that degrade the ECM, GF, and cells necessary for wound healing to occur. Cellular and acellular matrix products can be used in the management of a variety of chronic wounds including venous, diabetic, and pressure ulcers and other conditions such as burns, epidermolysis bullosa, pyoderma gangrenosum, and surgical wounds. These matrices provide cells, GF, and other key elements that act as a scaffold and promote reepithelialization and revascularization of the wound bed. METHODS: This article focuses on cellular and acellular matrix products that have been well-studied clinically with positive results in randomized clinical trials and widely available matrices for chronic nonhealing wounds. We present trial results as well as their indications, techniques, and outcomes. RESULTS: There are a variety of matrix products available on the market. Some of these products are used to treat chronic wounds, for example, diabetic foot ulcers, venous leg ulcers, pyoderma gangrenosum, and pressure ulcers. In this review, we found that wounds of different etiologies have been treated with a variety of matrices, with successful outcomes compared with standard wound care. CONCLUSIONS: Both cellular and acellular matrix products are useful in the management of a variety of chronic wounds. These matrices provide cells, GF, and other key elements that promote reepithelialization and revascularization of the wound bed while preventing degradation of the ECM. The treatment of chronic wounds with matrix products in combination with standard wound care has been proven to aid in wound healing when added to standard of care. PMID- 27556755 TI - The Role of Dermal Matrices in Treating Inflammatory and Diabetic Wounds. AB - BACKGROUND: Dermal matrices are used to improve healing in both acute and chronic wounds including diabetic and lower extremity wounds, burns, trauma, and surgical reconstruction. The use of dermal matrices for the closure of inflammatory ulcerations is less frequent but growing. Currently available products include decellularized dermis and semisynthetic matrices. METHODS: A review of the published literature was performed to identify reports that use acellular dermal matrices in diabetic and inflammatory wounds. Studies were evaluated for quality and outcomes, and a level of evidence was assigned according to the American Society of Plastic Surgeons' Rating Levels of Evidence. Case studies from the authors' experience are also presented. RESULTS: Seventeen primary studies evaluating the use of dermal matrices in diabetic ulcers were identified with 2 based on level I data. There are no prospective clinical trial reports of their use in atypical or inflammatory wounds, but there are several case studies. CONCLUSIONS: Treatment of diabetic and inflammatory wounds may include both medical and surgical modalities. The use of dermal matrices can be a useful adjunct, but their optimal use will require future clinical studies. PMID- 27556756 TI - Dressing and Diabetic Foot Ulcers: A Current Review of the Evidence. AB - BACKGROUND: The outcome of ulcers of the foot in diabetes is generally poor with around 1 in 10 resulting in the loss of a limb. There is an urgent need for the development of interventions to improve the outcome for patients. To date, however, the evidence base to support many of the interventions in common use, including wound dressings, is poor. METHODS: This article summarizes the findings of systematic reviews of the subject published between 2006 and 2014 and covers all relevant articles in any language, as well as comments on certain newer publications. RESULTS: The 3 consecutive systematic reviews selected a total of 207 articles that met the predefined criteria from a total of 5,632 identified. These included articles on a very wide range of interventions designed to be applied to ulcers of the foot in diabetes to promote wound healing. CONCLUSIONS: The available data suggest that although some newer therapies show promise, few published studies were of high quality, and the majority were susceptible to bias. More work is needed to substantiate the role of available dressings and wound care products in day-to-day clinical practice. Future work will require studies to be performed to a higher standard than many of those reviewed here and should establish not just clinical effectiveness but cost-effectiveness. The conclusions drawn from the studies of diabetic foot ulcers (DFUs) might apply to the management of other types of chronic wounds. PMID- 27556757 TI - Evidence-Based Scar Management: How to Improve Results with Technique and Technology. AB - BACKGROUND: Scars represent the visible sequelae of trauma, injury, burn, or surgery. They may induce distress in the patient because of their aesthetically unpleasant appearance, especially if they are excessively raised, depressed, wide, or erythematous. They may also cause the patient symptoms of pain, tightness, and pruritus. Numerous products are marketed for scar prevention or improvement, but their efficacy is unclear. METHODS: A literature review of high level studies analyzing methods to prevent or improve hypertrophic scars, keloids, and striae distensae was performed. The evidence from these articles was analyzed to generate recommendations. Each intervention's effectiveness at preventing or reducing scars was rated as none, low, or high, depending on the strength of the evidence for that intervention. RESULTS: For the prevention of hypertrophic scars, silicone, tension reduction, and wound edge eversion seem to have high efficacy, whereas onion extract, pulsed-dye laser, pressure garments, and scar massage have low efficacy. For the treatment of existing hypertrophic scars, silicone, pulsed-dye laser, CO2 laser, corticosteroids, 5-fluorouracil, bleomycin, and scar massage have high efficacy, whereas onion extract and fat grafting seem to have low efficacy. For keloid scars, effective adjuncts to excision include corticosteroids, mitomycin C, bleomycin, and radiation therapy. No intervention seems to have significant efficacy in the prevention or treatment of striae distensae. CONCLUSION: Although scars can never be completely eliminated in an adult, this article presents the most commonly used, evidence based methods to improve the quality and symptoms of hypertrophic scars, as well as keloid scars and striae distensae. PMID- 27556758 TI - The Role of Pressure Offloading on Diabetic Foot Ulcer Healing and Prevention of Recurrence. AB - BACKGROUND: An increased plantar pressure is a causative factor in the development of plantar foot ulcers in people with diabetes mellitus, and ulcers are a precursor of lower extremity amputation. METHODS: In this article, the evidence is reviewed that relieving areas of increased plantar pressure (ie, offloading) can heal plantar foot ulcers and prevent their recurrence. RESULTS: Noninfected, nonischemic neuropathic plantar forefoot ulcers should heal in 6 to 8 weeks with adequate offloading. Recent meta-analyses and systematic reviews show that nonremovable knee-high devices are most effective. This is probably because they eliminate the problem of nonadherence with the use of a removable device. Studies show a large discrepancy between evidence-based recommendations on offloading and what is used in clinical practice. Many clinics continue to use methods that are less effective or have not been proven to be effective, while ignoring evidence-based methods. Strategies are proposed to address this issue, notably the adoption and implementation of recent international guidelines by professional societies and a stronger focus of clinicians on expedited healing. For the prevention of plantar foot ulcer recurrence in high-risk patients, 2 recent trials have shown that the incidence of recurrence can be significantly reduced with custom-made footwear that has a demonstrated pressure-relieving effect through guidance by plantar pressure measurements, under the condition that the footwear is worn. CONCLUSION: This review helps to inform clinicians about effective offloading treatment for healing plantar foot ulcers and preventing their recurrence. PMID- 27556759 TI - What Role Does Function Play in Deciding on Limb Salvage versus Amputation in Patients With Diabetes? AB - BACKGROUND: Patients with diabetic foot disease are at an increased risk for lower extremity amputation (LEA), premature mortality, and reduced health-related quality of life. In the setting of chronic infection, significant tissue loss, and/or an unstable deformity, limb salvage may not be possible, and major amputation is necessary. METHODS: The primary goal of this study was to review the literature with an emphasis on the functional aspects associated with successful limb salvage versus major LEA. A secondary goal was to review the epidemiology, quality of life, mortality, and energy expenditure associated with diabetic foot disease. RESULTS: After major LEA, patients with diabetes are 3 times more likely to die within 1 year of surgery compared with patients who have not undergone LEA. Only two thirds of diabetic patients who undergo major LEA will ambulate with a prosthesis. This increased risk of death is not fully explained by complications of diabetes mellitus such as heart attack, stroke, or kidney failure. Preservation of lower extremity function is the primary goal of treatment, and reconstructive surgery should strive to achieve a plantigrade foot that is ulcer free and stable. Patients who have undergone successful limb salvage fear major amputation more than death. The energy costs of ambulation after LEA increase as the site of LEA becomes more proximal. CONCLUSIONS: Major LEA is a devastating complication in patients with diabetes. Once amputation becomes medically necessary, preoperative evaluation with a clinic specializing in amputations is very beneficial for these patients. PMID- 27556761 TI - Discussion: What Role Does Function Play in Deciding on Limb Salvage versus Amputation in Patients with Diabetes? PMID- 27556762 TI - Modalities to Treat Venous Ulcers: Compression, Surgery, and Bioengineered Tissue. AB - BACKGROUND: Venous leg ulcers (VLUs) represent the most common ulcers of the lower extremity. VLUs are notorious for delayed and prolonged healing with high rates of recurrence. Most patients with VLUs also have significant comorbidities that interfere with primary wound healing. Thus, caring for patients with VLUs requires an interdisciplinary approach that addresses the abnormal venous anatomy and the downstream effects that lead to inflammation, ulceration, and a hostile wound microenvironment. METHODS: The current literature regarding venous ulcer treatment with an emphasis on compression, surgical options, and use of bioengineered tissue was reviewed. A combination of society guidelines, Cochrane reviews, and over 80 primary articles with high-level evidence were utilized to develop this summary and algorithm for an integrated approach to treating patients with venous ulcers. Details regarding compression modalities and venous diagnostic imaging are presented to help the clinician understand the rationale for using these technologies. RESULTS: The comprehensive approach to the patient with chronic venous insufficiency (CVI) includes advances in compression, diagnostics, minimally invasive surgical treatment of venous disease, wound bed preparation, and bioengineered skin and soft tissue substitutes. An algorithm that incorporates early treatment of the ulcer and the venous disease leading to healing with prevention of recurrence is presented. CONCLUSIONS: Utilizing guidelines that incorporate evidence-based modalities will lead to the highest quality outcomes with the most appropriate resource utilization. A proactive approach to treating venous disease will alleviate suffering and prevent the long term sequelae of CVI. PMID- 27556763 TI - The "Current Concepts in Wound Healing: Update 2016" Supplement. PMID- 27556760 TI - Biology and Biomarkers for Wound Healing. AB - BACKGROUND: As the population grows older, the incidence and prevalence of conditions that lead to a predisposition for poor wound healing also increase. Ultimately, this increase in nonhealing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has and will continue to be the leading pathway to the discovery of therapeutic targets, as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of nonhealing patients for whom biomarker-guided approaches may aid in healing. METHODS: A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. RESULTS: Currently, biomarkers are being identified using biomaterials sourced locally from human wounds and/or systemically using high-throughput "omics" modalities (genomic, proteomic, lipidomic, and metabolomic analysis). In this review, we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum, including those measured in tissue specimens, for example, beta-catenin and c-myc, wound fluid, matrix metalloproteinases and interleukins, swabs, wound microbiota, and serum, for example, procalcitonin and matrix metalloproteinases. CONCLUSIONS: Identification of numerous potential biomarkers using different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity and consistent implementation of these biomarkers, as well as an emphasis on efficacious follow-up therapeutics, is necessary for transition of this technology to clinically feasible point-of-care applications. PMID- 27556764 TI - Lymphedema: Surgical and Medical Therapy. AB - BACKGROUND: Secondary lymphedema is a dreaded complication that sometimes occurs after treatment of malignancies. Management of lymphedema has historically focused on conservative measures, including physical therapy and compression garments. More recently, surgery has been used for the treatment of secondary lymphedema. METHODS: This article represents the experience and treatment approaches of 5 surgeons experienced in lymphatic surgery and includes a literature review in support of the techniques and algorithms presented. RESULTS: This review provides the reader with current thoughts and practices by experienced clinicians who routinely treat lymphedema patients. CONCLUSION: The medical and surgical treatments of lymphedema are safe and effective techniques to improve symptoms and improve quality of life in properly selected patients. PMID- 27556765 TI - What Heals Hidradenitis Suppurativa: Surgery, Immunosuppression, or Both? AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin that is a significant source of impaired quality-of-life for affected individuals. For patients with refractory disease, radical resection of all involved tissue may offer the only potential option for a cure. However, high rates of recurrence after wide local excision have led investigators to seek alternative therapeutic combinations. We present our experience and a literature review. METHODS: A comprehensive literature review (1982-2016) was performed on PubMed and Ovid MEDLINE, using key words relevant to HS. RESULTS: A total of 1842 publications were identified, and 15 publications were included in this review on: surgical intervention (n = 10), biologic therapy (n = 4), and joint surgical and biologic treatment (n = 1) of HS. The treatment type, level of evidence, and key findings are assessed and discussed. CONCLUSIONS: Recent trials demonstrating the safety and efficacy of biologic therapy alone in patients with moderate-to severe HS have spurred questions regarding the potential utility of these agents as adjuncts to more traditional surgical interventions. The results of the literature search advocate a role for radical resection and biologic therapy in the setting of moderate-to-severe disease. Preliminary results from limited case series suggest a potential role for combined management in the setting of advanced, recalcitrant disease. PMID- 27556766 TI - Discussion: What Heals Hidradenitis Suppurativa: Surgery, Immunosuppression, or Both? PMID- 27556767 TI - Prevention of Pressure Ulcers in the Acute Care Setting: New Innovations and Technologies. AB - BACKGROUND: Pressure ulcers (PUs) challenge many in the healthcare field requiring costly and complex care. PUs result from prolonged ischemia and subsequent soft-tissue injury caused by unrelieved pressure over a bony prominence. Proper risk assessment and implementation of prevention strategies for PUs are crucial to providing comprehensive care while reducing healthcare costs. The emphasis has led to the expansion of research in PU prevention technologies in the recent years. The aim of this review is to present an evidence-based summary of some of the new innovations in PU prevention. METHODS: A literature search was performed. Articles were included if the article discussed the cost, prevalence, assessment, diagnosis, and/or prevention of PUs. The literature search was limited to 2013 to 2016. RESULTS: A total of 1393 potential studies were identified using the search criteria. Three hundred fifty three articles were reviewed and when possible, preference for inclusion was given to those studies with a higher level of evidence or those discussing novel ideas/innovations. CONCLUSION: The summary of topics explored includes the following: the use of risk assessment scales as an adjunct in risk identification, the benefit of alternative support surfaces to aid in prevention as compared with standard hospital mattresses, effective repositioning strategies, silicone prophylactic dressing for shear reduction, microclimate control, nutritional considerations, use of electrical stimulation for spinal cord injury patients, and the importance of patient participation. PMID- 27556768 TI - Building a Multidisciplinary Hospital-Based Wound Care Center: Nuts and Bolts. AB - BACKGROUND: A hospital-based wound care center provides an important platform for the multidisciplinary approach to wound care. The colocation of specialists is an ideal working environment for the efficient delivery of quality care of the complex wound through daily communication and shared resources. METHODS: We describe the critical components necessary in building a hospital-based wound care center. Furthermore, the experience at the authors' institution in developing the multidisciplinary approach is discussed. RESULTS: Readily available ancillary services, specially trained personnel, continuum of care from the outpatient clinic to admission to surgery, and inpatient and outpatient post operative care all contribute to a process that is especially amenable to the care of the complex wound. CONCLUSIONS: The final goal is to return the patient to the best quality of life achievable given his or her wound or disability. The aim of this study is to present the authors' experiences and provide insight for others who may want to build this model within their institutions. PMID- 27556769 TI - The Role of Telemedicine in Wound Care: A Review and Analysis of a Database of 5,795 Patients from a Mobile Wound-Healing Center in Languedoc-Roussillon, France. AB - BACKGROUND: Telemedicine in wound care is an evolving method of information technology and telecommunication designed to provide health care at a distance. Given the visual nature of wound care, telemedicine has many potential applications within this field. The authors will review the current status of wound care and telemedicine. METHODS: A comprehensive literature review of articles published on telemedicine in wound care was performed. Articles were selected for their relevance to wound healing and then reviewed for their discussion on the potential applications, benefits, and limitations to telemedicine in wound care. The CICAT network data were reviewed including 5,794 patients between January 2005 and October 2015. Clinical efficacy and medicoeconomic results were analyzed. RESULTS: Current literature suggests a myriad of potential benefits of telemedicine in wound care, often citing increased access to professional expertise in remote and rural settings, as well as cost savings. The CICAT wound network in France analyzed wounds, which were principally pressure ulcers (44%), leg ulcers (24%), and diabetic foot ulcers (8%). Results demonstrated 75% of wounds improved or healed, a 72% reduction in the number of hospitalizations, and 56% reduction in ambulance transfers to wound healing centers. CONCLUSIONS: There is an increasing demand for assistance from professionals not specialized in wound healing, facing complex wounds. The goal is to enable the spread of expertise beyond major medical centers. Several limitations and barriers to the application of telemedicine in all settings are evident, including over diagnosis, dependence on a functional telecommunication system, and various legal aspects. The CICAT network in France provides an example of a how telemedicine may be of benefit in wound care, although it is important to note that in other countries, such as the United States, legal constraints and credentialing concerns may make telemedicine extremely complicated. PMID- 27556770 TI - Evidence-Based Medicine: Wound Closure. AB - LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Describe various wound closure techniques available to the modern plastic surgeon, including the indications and contraindications of each. 2. Explain the fundamental concepts of wound healing as it relates to reconstruction. 3. Understand the role of commonly used reconstructive adjuncts such as negative pressure wound therapy, dermal substitutes, and tissue expansion. 4. Assess the important patient factors that may influence the strategy for surgical wound closure. SUMMARY: Successful wound closure requires a comprehensive approach that includes consideration of suitable surgical techniques and critical patient factors. A clear understanding of key concepts such as wound healing, flap design, and patient risk assessment is imperative to a favorable outcome. In this Maintenance of Certification/Continuing Medical Education article, the reader is provided a summary of the available surgical options for wound closure and a discussion of the algorithm used to choose the most appropriate reconstructive strategy. PMID- 27556771 TI - Discussion: Biology and Biomarkers for Wound Healing. PMID- 27556773 TI - Financial Disclosure Appendix for "Current Concepts in Wound Healing: Update 2016". PMID- 27556772 TI - The Role of Stem Cell Therapeutics in Wound Healing: Current Understanding and Future Directions. AB - BACKGROUND: Chronic wounds present unique challenges for healthcare providers as they place patients at increased risk for various morbidities and mortality. Advances in wound care technology have expanded the treatment options available for wound management, but few products fully address the underlying core deficiencies responsible for the development of poorly healing wounds. In the future, addressing these derangements will undoubtedly play a key role in the treatment of these patients. Broad enthusiasm has surrounded the field of stem cell biology, which has shown great promise in repairing damaged tissues across numerous disease phenotypes. METHODS: In this review, we provide a comprehensive review of the literature and evaluate the present landscape of wound therapeutics while discussing the rationales and allure behind stem cell-based products. We further propose 2 challenges that remain as new stem cell-based therapies are being developed and as this technology moves toward clinical translation. RESULTS: Given the relatively young age of this newer technology in wound healing, numerous challenges continue to surround its effective use including identifying the ideal population of stem cells to use and determining the optimal cell delivery method. However, significant forward progress has been made, with several clinical trials beginning to demonstrate reliable clinical benefit. CONCLUSION: The upward trajectory of stem cell technologies provides an exciting opportunity to positively impact patient outcomes through the controlled application of regenerative cell-based therapy. PMID- 27556774 TI - Current Concepts in Tissue Engineering: Skin and Wound. AB - BACKGROUND: Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. METHODS: Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. RESULTS: Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. CONCLUSIONS: Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds. PMID- 27556775 TI - Evidence-Based Strategies to Reduce Postoperative Complications in Plastic Surgery. AB - Reconstructive plastic surgery is vital in assisting patients with reintegration into society after events such as tumor extirpation, trauma, or infection have left them with a deficit of normal tissue. Apart from performing a technically sound operation, the plastic surgeon must stack the odds in the favor of the patient by optimizing them before and after surgery. The surgeon must look beyond the wound, at the entire patient, and apply fundamental principles of patient optimization. This article reviews the evidence behind the principles of patient optimization that are commonly used in reconstructive surgery patients. PMID- 27556776 TI - Update on the Role of Infection and Biofilms in Wound Healing: Pathophysiology and Treatment. AB - BACKGROUND: Chronic wounds, and among these infected diabetic foot ulcers, are a worldwide problem. The poor treatment outcomes result in high healthcare costs, amputations, a decreased quality of life, and an increased mortality. These outcomes are influenced by several factors, including biofilm formation. A biofilm consists of pathogenic bacteria that are encased in an exopolysaccharide layer and communicate through secretion of signaling molecules. Bacteria that live in a biofilm are refractory to host responses and treatment. METHODS: We performed a nonsystematic review of the currently published to-date medical biofilm literature. The review summarizes the evidence of biofilm in chronic wounds, the role of biofilm in wound healing, detection of biofilm, and available antibiofilm treatments. Articles containing basic science and clinical research, as well as systematic reviews, are described and evaluated. The articles have variable levels of evidence. All articles have been peer reviewed and meet the standards of evidence-based medicine. RESULTS: Both animal and human studies have identified biofilm in chronic wounds and have suggested that healing might be influenced by its presence. A promising development in biofilm detection is rapid molecular diagnostics combined with direct microscopy. This technique, rather than classic culture, might support individualized treatment in the near future. A wide range of treatments for chronic wounds also influence biofilm formation. Several agents that specifically target biofilm are currently being researched. CONCLUSIONS: Biofilm formation has a substantial role in chronic wounds. Several diagnostic and therapeutic methods against biofilm are currently being developed. PMID- 27556777 TI - Nutrition and Chronic Wounds: Improving Clinical Outcomes. AB - There is increasing awareness that chronic wound healing is very dependent on the patient's nutritional status, but there are no clearly established and accepted assessment protocols or interventions in clinical practice. Much of the data used as guidelines for chronic wound patients are extrapolated from acutely wounded trauma patients, but the 2 groups are very different patient populations. While most trauma patients are young, healthy, and well-nourished before injury, the chronic wound patient is usually old, with comorbidities and frequently malnourished. We suggest the assumption that all geriatric wound patients are malnourished until proved otherwise. Evaluation should include complete history and physical and a formal nutritional evaluation should be obtained. Laboratory studies can be used in conjunction with this clinical information to confirm the assessment. While extensive studies are available in relation to prevention and treatment of pressure ulcers and perioperative nutrition, less is known of the effect of nutritional deficits and supplementation of the diabetic foot ulcer and venous stasis ulcer patient. This does not necessarily mean that nutritional support of these patients is not helpful. In the pursuit of wound healing, we provide systemic support of cardiac and pulmonary function and cessation of smoking, improve vascular inflow, improve venous outflow, decrease edema, and treat with hyperbaric oxygen. If we address all of these other conditions, why would we not wish to support the most basic of organismal needs in the form of nutrition? PMID- 27556778 TI - Introduction to "Current Concepts in Wound Healing: Update 2016". PMID- 27556779 TI - Current Concepts in Debridement: Science and Strategies. AB - BACKGROUND: The establishment of a healthy wound bed through adequate debridement of infected, senescent, and/or devitalized tissue is central to the progression of normal wound healing. Although a variety of surgical and nonsurgical strategies have been proposed, none have proven completely effective in all settings. This review focuses on the principles and techniques of modern debridement practices employed in the management of complex wounds. METHODS: A comprehensive review of the PubMed/Medline and Ovid databases was performed to identify basic science and clinical studies using key words most relevant to biofilm, debridement, and wound healing. English language articles that were peer reviewed and that met the standard of evidence-based medicine were included. Level of evidence for various debridement approaches was rated utilizing the American Society of Plastic Surgeons Rating Levels of Evidence and Grading Recommendations. RESULTS: The value of both operative and nonoperative debridement techniques, their indications, and limitations are described. With an emphasis placed on surgical debridement, this review highlights technical adjuncts that can be used to optimize wound bed preparation, including preoperative topical staining of the wound, as well as the use of color-guided endpoints to prevent removal of excess healthy tissue. The indications for using temporizing measures for wound control such as negative pressure wound therapy with and without installation are also discussed. CONCLUSION: Optimal management requires a multimodal approach that centers around operative debridement and incorporates the use of adjunctive measures to facilitate the removal of infected tissue, biofilm, and/or senescent cells that impede the progression of normal wound healing. PMID- 27556780 TI - Advanced Technologies to Improve Wound Healing: Electrical Stimulation, Vibration Therapy, and Ultrasound-What Is the Evidence? AB - BACKGROUND: Cellular energy is required for the healing cascade to occur. A combination of cells, cytokines, chemokines, tissue perfusion, an extracellular matrix, and local forces are also required to allow for human tissue repair to proceed. Although there are many examples of treatment options, energy-based therapies are the least understood, appreciated, and employed by practicing wound care physicians. The recent growth of tissue engineering has encouraged researchers to employ both electrical stimulation and therapeutic ultrasound (US) to stimulate cells, induce migration, and modify tissue constructs. METHODS: The authors have reviewed the literature on electrical stimulation, US, and vibrational therapy and are providing an update to a prior 2007 publication on this topic. The hope was to provide a broad exposure to these treatments but not to create a comprehensive review. A table of evidence was generated from the recent literature to help guide treatment decisions for the clinician. RESULTS: In the current literature, there is much debate over which treatment modality, dosage levels, and timing are optimal. There are numerous in-vitro-based publications that describe mechanism of action and several clinical articles that describe effectiveness of electrical stimulation and US, but few well-controlled and/or randomized trials. The absence of level one evidence has hindered the adoption of these techniques throughout the years. Three energy-based treatment options, electrical stimulation, vibration, and US, will be reviewed along with possible clinical applications CONCLUSIONS: : Although most trials are underpowered with inconsistent treatment settings, physical therapy modality use is increasing in the clinical community. Recent guidelines reference the use of these treatments with increasing evidence level recommendations. At the present time, electrical stimulation carries the greatest level of evidence for clinical use. PMID- 27556781 TI - Wound Healing: Part I. Basic Science. AB - LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the basic physiologic events in normal wound healing. 2. Understand the differences in healing among skin, bone, cartilage, and tendon. 3. Identify factors that may compromise or delay wound healing. 4. Describe methods for optimal closure of a wound. SUMMARY: Understanding the physiology and pathophysiology of normal wound healing and potential impediments to its end will allow the plastic surgeon to maximize postoperative outcomes and, in some instances, avoid unnecessary surgical interventions. Continuous advancements in our understanding of this process require frequent reviews of available data to permit reliable, evidence-based recommendations for clinical application. This is the first of a two-part article summarizing the science and clinical recommendations necessary for successful wound healing. PMID- 27556782 TI - Synthesis and Characterization of Some New N-Glycosides of Pyridine-2,6-bis Carboxamides Derivatives. AB - A series of novel pyridine-bridged 2,6-bis-carboxamide N-beta-glycosides and Schiff's bases has been prepared starting from 2,6-bis-carboxamide pyridine hydrazide, which on treatment with appropriate monosaccharides, aromatic or heterocyclic aldehydes, and indoline-2,3-dione derivatives afforded the corresponding sugar hydrazones and pyridine-bridged 2,6-bis-carboxamide Schiff's bases. PMID- 27556783 TI - 4'-Epi-DNA: A DNA Mimic Containing 4'-hydroxymethyl-alpha-l-Xylo-Thymidine with Compact Backbone like RNA. AB - Synthesis of C4'-epi-DNA containing 3'-> 5" linkages is reported for the first time. Crystal structure study of the monomer indicated that though the dihedral angle O3'-C3'-C4'-C5" in this case would be like in RNA, the sugar conformation would remain like that in DNA. The study of the effect of this backbone configuration in DNA with respect to its binding to cDNA and RNA is reported in this note. PMID- 27556784 TI - A First Microwave-Assisted Synthesis of a New Class of Purine and Guanine Thioglycoside Analogs. AB - A first microwave-assisted synthesis of a new class of novel purine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyrazolo[1,5-a]pyrimidine-7 thiolate and 7-mercaptopyrazolo[1,5-a]pyrimidine derivatives via condensation of 5-amino-1H-pyrazoles with sodium 2,2-dicyanoethene-1,1-bis(thiolate) salts or 2 (dimercaptomethylene)malononitrile, respectively, under microwave irradiation, followed by coupling with halo sugars to give the corresponding purine thioglycoside analogs. The obtained purines and purines thioglycosides derivatives were evaluated in vitro against lung (A549), colon (HCT116), liver (HEPG2), and prostate (PC3) cancer cell lines. Some of these compounds (5b, 5d, 5f, and 9a-d) exhibited little potency toward the four cell lines. On the other hand, compound 5a elicited higher cytotoxicity on both prostate (PC3) and colon (HCT116), respectively, while it was found moderate on lung (A549), and inactive on liver (HEPG2). Moreover, compound 5c was found moderate with LC50 values 52.0 88.9 MUM for almost all the cell lines. PMID- 27556785 TI - Synthesis and Evaluation of 2'-Deoxy-2'-Spirodiflurocyclopropyl Nucleoside Analogs. AB - The preparation of 2'-deoxy-2'-siprodifluorocyclopropany-lnucleoside analogs has been achieved from alpha-d-glucose in several steps. The key step in the synthesis was the introduction of the difluorocyclopropane through a difluorocarbene type reaction at the 2'-position. Then, a series of novel 2' deoxy-2'-spirodifluorocyclopropanyl nucleoside analogs were synthesized using the Vorbruggen method. All the synthesized nucleosides were characterized and subsequently evaluated against hepatitis C and influenza A virus strains in vitro. PMID- 27556786 TI - Accuracy of software-assisted contour propagation from planning CT to cone beam CT in head and neck radiotherapy. AB - BACKGROUND: Autocontouring improves workflow in computed tomography (CT)-based dose planning, but could also potentially play a role for optimal use of daily cone beam CT (CBCT) in adaptive radiotherapy. This study aims to determine the accuracy of a deformable image registration (DIR) algorithm for organs at risk (OAR) in the neck region, when applied to CBCT. MATERIAL AND METHODS: For 30 head and neck cancer (HNC) patients 14 OARs including parotid glands, swallowing structures and spinal cord were delineated. Contours were propagated by DIR from CT to the CBCTs of the first and last treatment fraction. An indirect approach, propagating contours to the first CBCT and from there to the last CBCT was also tested. Propagated contours were compared to manually corrected contours by Dice similarity coefficient (DSC) and Hausdorff distance (HD). Dose was recalculated on CBCTs and dosimetric consequences of uncertainties in DIR were reviewed. RESULTS: Mean DSC values of >=0.8 were considered adequate and were achieved in tongue base (0.91), esophagus (0.85), glottic (0.81) and supraglottic larynx (0.83), inferior pharyngeal constrictor muscle (0.84), spinal cord (0.89) and all salivary glands in the first CBCT. For the last CBCT by direct propagation, adequate DSC values were achieved for tongue base (0.85), esophagus (0.84), spinal cord (0.87) and all salivary glands. Using indirect propagation only tongue base (0.80) and parotid glands (0.87) were >=0.8. Mean relative dose difference between automated and corrected contours was within +/-2.5% of planed dose except for esophagus inlet (-4.5%) and esophagus (5.0%) for the last CBCT using indirect propagation. CONCLUSION: Compared to manually corrected contours, the DIR algorithm was accurate for use in CBCT images of HNC patients and the minor inaccuracies had little consequence for mean dose in most clinically relevant OAR. The method can thus enable a more automated segmentation of CBCT for use in adaptive radiotherapy. PMID- 27556787 TI - Ionizing radiation exposure in interventional cardiology: current radiation protection practice of invasive cardiology operators in Lithuania. AB - Ionizing radiation management is among the most important safety issues in interventional cardiology. Multiple radiation protection measures allow the minimization of x-ray exposure during interventional procedures. Our purpose was to assess the utilization and effectiveness of radiation protection and optimization techniques among interventional cardiologists in Lithuania. Interventional cardiologists of five cardiac centres were interviewed by anonymized questionnaire, addressing personal use of protective garments, shielding, table/detector positioning, frame rate (FR), resolution, field of view adjustment and collimation. Effective patient doses were compared between operators who work with and without x-ray optimization. Thirty one (68.9%) out of 45 Lithuanian interventional cardiologists participated in the survey. Protective aprons were universally used, but not the thyroid collars; 35.5% (n = 11) operators use protective eyewear and 12.9% (n = 4) wear radio-protective caps; 83.9% (n = 26) use overhanging shields, 58.1% (n = 18)-portable barriers; 12.9% (n = 4)-abdominal patient's shielding; 35.5% (n = 11) work at a high table position; 87.1% (n = 27) keep an image intensifier/receiver close to the patient; 58.1% (n = 18) reduce the fluoroscopy FR; 6.5% (n = 2) reduce the fluoro image detail resolution; 83.9% (n = 26) use a 'store fluoro' option; 41.9% (N = 13) reduce magnification for catheter transit; 51.6% (n = 16) limit image magnification; and 35.5% (n = 11) use image collimation. Median effective patient doses were significantly lower with x-ray optimization techniques in both diagnostic and therapeutic interventions. Many of the ionizing radiation exposure reduction tools and techniques are underused by a considerable proportion of interventional cardiology operators. The application of basic radiation protection tools and techniques effectively reduces ionizing radiation exposure and should be routinely used in practice. PMID- 27556788 TI - Non-Prostate-Specific Membrane Antigen-Avid Metastatic Lung Nodule From Primary Prostatic Adenocarcinoma. AB - Ga-prostate-specific membrane antigen (PSMA) PET/CT is increasingly used to evaluate recurrent prostatic malignancy due to its high specificity. A 56-year old man with previous history of treated prostate cancer 4 years earlier presented with rising prostate-specific antigen level and underwent Ga-PSMA PET/CT, which demonstrated an enlarging pulmonary nodule without PSMA avidity. The pulmonary nodule, however, showed moderate uptake on a corresponding FDG PET/CT study, suspicious of primary lung malignancy. Cytological and histopathological examination of the pulmonary nodule confirmed a metastatic deposit from ductal prostatic adenocarcinoma, an uncommon variant of prostatic malignancy. PMID- 27556789 TI - Metabolic Tumor Volume and Total Lesion Glycolysis in PET/CT Correlate With the Pathological Findings of Colorectal Cancer and Allow Its Accurate Staging. AB - INTRODUCTION: PET/CT plays an important role in cancer diagnosis. Recently, novel metabolic parameters in PET/CT such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported to be diagnostic and prognostic biomarkers of various cancers. We evaluated the diagnostic value of these metabolic parameters in colorectal cancer (CRC). METHODS: The study included 138 patients who underwent surgical resection of CRCs between August 2012 and March 2014. The MTVs and TLGs of tumors were measured using various SUV thresholds. The diagnostic abilities of the metabolic parameters were analyzed using ROC curves and classification and regression trees. RESULTS: The AUCs of the MTVs and TLGs for predicting T stage (0.881-0.892) were significantly higher than the AUC of the SUVmax (0.824). In the M stage, the AUCs of MTVs and TLGs (0.688-0.723) were significantly higher than that of the SUVmax (0.606). Recursive partitioning applying classification and regression trees demonstrated that the optimal cutoff values of the most important variables for discriminating T, N, and M stages are MTV2.5 = 9.35 and 63.33 mL, TLG50% = 328.1, and TLG50% = 94.81, respectively. CONCLUSION: Metabolic tumor volumes and TLGs in PET/CT are reliable diagnostic biomarkers. Using these parameters, more accurate preoperative diagnoses for CRC can be made. PMID- 27556790 TI - 18F-FDG PET/CT Demonstrating Malignant Degeneration of a Uterine Fibroid. AB - Whereas benign leiomyoma of the uterus (fibroid) is very common, malignant degeneration of such fibroids to leiomyosarcoma is rare. Anatomical imaging with CT or MRI cannot differentiate between larger leiomyoma and leiomyosarcoma. Imaging with F-FDG PET/CT can be helpful in differentiating the two. High-grade F FDG uptake in uterine fibroids is suspected and warrants surgical excision for further evaluation. We present such as case of a 42-year-old premenopausal woman where F-FDG PET/CT helped in making the diagnosis of malignant degeneration of uterine fibroid. PMID- 27556791 TI - Nonneoplastic Neuroma After Radical Prostatectomy Is Not a Mimicker of Lymph Node Metastases on 68Ga-PSMA Ligand PET/CT. AB - Traumatic neuroma is frequently observed after surgery. PSMA expression has been demonstrated in neoplastic nerve sheath tumors, which may mimic metastases on PSMA imaging. In this case, histopathologic evaluation of a pelvic lesion with assumed intense tracer uptake on Ga-PSMA ligand PET/CT in a patient with biochemical recurrence of prostate cancer revealed an amputation neuroma. However, immunohistochemical evaluation showed absent PSMA expression, and follow up PET confirmed persistence of the metastasis. Unlike neoplastic nerve sheath tumors, traumatic neuroma does not show PSMA expression and is not a mimicker of metastases on Ga-PSMA PET/CT. PMID- 27556792 TI - Brain Metastases Mimicking Hyperostosis Frontalis Interna on 99mTc HDP Bone Scintigraphy. AB - Symmetric bifrontal uptake of bone-seeking agents is usually considered as the main feature of hyperostosis frontalis interna in postmenopausal elderly women. This finding is not uncommon in elderly women because of the change in their hormonal level. However, in the present case, a 66-year-old woman with intra axial brain metastases of breast cancer showed symmetric bifrontal uptake on bone scintigraphy. Therefore, symmetric bifrontal uptake should not always be considered as a definite indicator of hyperostosis frontalis interna. Further evaluation such as SPECT/CT is needed for evaluation of brain metastases especially in cancer patients. PMID- 27556793 TI - Optimal Time Points for Scintigraphic Imaging of Pleuroperitoneal Shunts. AB - OBJECTIVE: Nuclear imaging can confirm pleuroperitoneal shunt as the cause of pleural effusion. No society guidelines exist for scintigraphic pleuroperitoneal shunt detection. Our institutional protocol was evaluated to determine optimal imaging time points for shunt detection. METHODS: Pleuroperitoneal shunt studies over 4 years were blindly reviewed by 2 nuclear radiologists. Data from blinded review included presence or absence of pleuroperitoneal shunt, laterality of shunt and time points for shunt detection. RESULTS: Chart review yielded 30 studies. Three cases were excluded because of improper injection. Imaging was positive for pleuroperitoneal shunt in 81% (22/27) of cases. In positive cases, activity was identified in the right hemithorax in 82% (18/22), left hemithorax in 9% (2/22), and bilaterally in 9% (2/22). One-hour imaging demonstrated 91% (20/22) of positive cases. The remaining 2 positive cases were negative at 1 hour but positive after 4 hours. No study was negative at 1 and 4 hours and positive at 24 hours. All negative cases (5/27) were confirmed on 24-hour imaging. CONCLUSIONS: The majority of positive pleuroperitoneal shunt examinations will demonstrate activity in the right hemithorax on 1-hour imaging. Although no case was negative at 1 and 4 hours and positive at 24 hours, imaging at 24 hours may still be necessary to confirm absence of shunt. Therefore, optimal imaging time points consist of early 1-hour and delayed 24-hour images if the 1-hour time point was negative. The 4-hour time point may be considered optional, thereby potentially optimizing patient safety and resource utilization. PMID- 27556794 TI - Serial 18F-FDG PET/CT Findings in a Patient With IgLON5 Encephalopathy. AB - We presented the serial FDG PET/CT brain scans of a 64-year-old woman with IgLON5 encephalopathy, which is a novel syndrome in association with antibodies to a neuronal cell adhesion protein named IgLON5, and FDG PET findings have not been characterized previously. For our case, the relatively hypermetabolism in primary sensorimotor cortices, basal ganglia, and cerebrum comparing to other cortical regions on the pretreatment FDG PET/CT was partially recovered on the follow-up FDG PET/CT scan after immunotherapy, corresponding with the alleviation of clinical syndromes. The metabolic change pattern was not similar as other types of autoimmune encephalitis. PMID- 27556795 TI - Aspecific Uptake of 68GA-PSMA in Paget Disease of the Bone. AB - Ga-PSMA plays an increasing role in prostate cancer management, but several instances of false positivity have now been recognized. We present a patient with metastatic prostatic carcinoma who also showed overexpression of PSMA in Paget disease of the humerus on Ga-PSMA PET. This probably relates to bone remodeling and increased vascularity. It is important to be aware of this aspecific uptake because its recognition may avoid overstaging and may alter the therapeutic choice. PMID- 27556796 TI - Deep Vein Thrombosis Presenting on Pulmonary Ventilation and Perfusion Scintigraphy. AB - A 52-year-old woman presenting with dyspnea was referred for a ventilation and perfusion scan (VQ). VQ images (with Tc-DTPA [diethylene triamine pentaacetic acid aerosol] and Tc-MAA [macroaggregated albumin]) initially appeared normal; however, count rates on perfusion images were similar to ventilation images, implying little Tc-MAA had reached the lungs. Spot images of the injected extremity demonstrated focal Tc-MAA accumulation worrisome for a venous thrombus, subsequently confirmed by Doppler ultrasound. Careful attention to relative radiotracer count rates on VQ scans is crucial to ensure diagnostic utility. In addition, abnormal low perfusion radiotracer counts may unveil other pathology with important clinical implications. PMID- 27556797 TI - 68Ga-PSMA PET/CT False-Positive Tracer Uptake in Paget Disease. AB - 65-year-old man with left-sided pelvic pain on evaluation was found to have features suggestive of either Paget disease or prostatic bone metastasis of the left hemipelvis based on Tc-MDP bone scan and MRI. Ga-PSMA PET/CT to assess the possibility of primary prostate cancer and if present to stage it helped to rule out prostate cancer because of absence of focal abnormal increased tracer uptake in the prostate gland. However, false-positive tracer uptake was noted in the left hemipelvis, which was subject to biopsy and histopathologically proven to be Paget disease involvement. PMID- 27556798 TI - MRI and FDG PET/CT Findings of Primary Orbit Leiomyosarcoma. AB - Primary leiomyosarcoma of the orbit is extremely rare. Here we report the case of a 32-year-old woman who presented with proptosis and diplopia of the left eye. MRI examination showed a solid mass in the left orbit with invasion to adjacent tissue, and the lesion had intense FDG uptake with SUVmax of 18.7 on F-FDG PET/CT. Primary orbit leiomyosarcoma was diagnosed by surgery-pathology. F-FDG PET/CT has an advantage in excluding secondary or metastatic orbit malignancy. PMID- 27556799 TI - Unusual Uptake of Radioiodine in a Subcutaneous Lipoma in a Patient With Differentiated Thyroid Cancer. AB - A 68-year-old man underwent adjuvant radioiodine therapy for follicular variant papillary thyroid carcinoma. Post-therapeutic whole-body I scan showed abnormal radioiodine uptake on the right side of back. SPECT/CT localized this abnormal activity from a small subcutaneous lesion with fat density between the right 10th and 11th rib. Under ultrasound-guided autopsy, the lesion was confirmed as lipoma. PMID- 27556800 TI - Serendipitous Detection of Hodgkin Lymphoma by 18F-NaF PET/CT. AB - A 17-year-old girl underwent F-NaF PET/CT to evaluate bone pain after an accident. The images did not identify any osseous lesion. However, there was a focally increased activity in the left upper chest, which corresponded to a partially calcified soft tissue mass in the mediastinum, suggestive of malignancy. The result led to subsequent F-FDG PET/CT imaging, which demonstrated intense activity in the mediastinal mass and in multiple cervical, supraclavicular, and mediastinal lymph nodes. Hodgkin lymphoma was diagnosed histopathologically following the biopsy. PMID- 27556801 TI - False Suggestion of Malignant Transformation of Benign Bone Tumor by 18F-FDG PET/CT: A Potential Pitfall. AB - A 68-year-old man underwent serial F-FDG PET/CT scan follow-up for lung cancer. Then 5.5 years after the initial F-FDG PET/CT scan, the presumed benign bone tumor in the left clavicle showed markedly increased FDG uptake during follow-up; in contrast, the Tc-MDP bone scan paradoxically exhibited no apparent interval change since last bone scan 5.5 years earlier. He underwent a CT-guided biopsy, and the pathological diagnosis was benign fibrous histiocytoma. The result was consistent with the lack of progression in Tc-MDP bone scan, whereas the F-FDG PET/CT scan gave a false-positive impression of malignant transformation. PMID- 27556803 TI - A new algorithm for "the LCS problem" with application in compressing genome resequencing data. AB - BACKGROUND: The longest common subsequence (LCS) problem is a classical problem in computer science, and forms the basis of the current best-performing reference based compression schemes for genome resequencing data. METHODS: First, we present a new algorithm for the LCS problem. Using the generalized suffix tree, we identify the common substrings shared between the two input sequences. Using the maximal common substrings, we construct a directed acyclic graph (DAG), based on which we determine the LCS as the longest path in the DAG. Then, we introduce an LCS-motivated reference-based compression scheme using the components of the LCS, rather than the LCS itself. RESULTS: Our basic scheme compressed the Homo sapiens genome (with an original size of 3,080,436,051 bytes) to 15,460,478 bytes. An improvement on the basic method further reduced this to 8,556,708 bytes, or an overall compression ratio of 360. This can be compared to the previous state-of-the-art compression ratios of 157 (Wang and Zhang, 2011) and 171 (Pinho, Pratas, and Garcia, 2011). CONCLUSION: We propose a new algorithm to address the longest common subsequence problem. Motivated by our LCS algorithm, we introduce a new reference-based compression scheme for genome resequencing data. Comparative results against state-of-the-art reference-based compression algorithms demonstrate the performance of the proposed method. PMID- 27556804 TI - Statistical modeling for sensitive detection of low-frequency single nucleotide variants. AB - BACKGROUND: Sensitive detection of low-frequency single nucleotide variants carries great significance in many applications. In cancer genetics research, tumor biopsies are a mixture of normal and tumor cells from various subpopulations due to tumor heterogeneity. Thus the frequencies of somatic variants from a subpopulation tend to be low. Liquid biopsies, which monitor circulating tumor DNA in blood to detect metastatic potential, also face the challenge of detecting low-frequency variants due to the small percentage of the circulating tumor DNA in blood. Moreover, in population genetics research, although pooled sequencing of a large number of individuals is cost-effective, pooling dilutes the signals of variants from any individual. Detection of low frequency variants is difficult and can be cofounded by sequencing artifacts. Existing methods are limited in sensitivity and mainly focus on frequencies around 2 % to 5 %; most fail to consider differential sequencing artifacts. RESULTS: We aimed to push down the frequency detection limit close to the position specific sequencing error rates by modeling the observed erroneous read counts with respect to genomic sequence contexts. 4 distributions suitable for count data modeling (using generalized linear models) were extensively characterized in terms of their goodness-of-fit as well as the performances on real sequencing data benchmarks, which were specifically designed for testing detection of low-frequency variants; two sequencing technologies with significantly different chemistry mechanisms were used to explore systematic errors. We found the zero-inflated negative binomial distribution generalized linear mode is superior to the other models tested, and the advantage is most evident at 0.5 % to 1 % range. This method is also generalizable to different sequencing technologies. Under standard sequencing protocols and depth given in the testing benchmarks, 95.3 % recall and 79.9 % precision for Ion Proton data, 95.6 % recall and 97.0 % precision for Illumina MiSeq data were achieved for SNVs with frequency > = 1 %, while the detection limit is around 0.5 %. CONCLUSIONS: Our method enables sensitive detection of low-frequency single nucleotide variants across different sequencing platforms and will facilitate research and clinical applications such as pooled sequencing, cancer early detection, prognostic assessment, metastatic monitoring, and relapses or acquired resistance identification. PMID- 27556802 TI - Influenza epidemiology and influenza vaccine effectiveness during the 2014-2015 season: annual report from the Global Influenza Hospital Surveillance Network. AB - The Global Influenza Hospital Surveillance Network (GIHSN) has established a prospective, active surveillance, hospital-based epidemiological study to collect epidemiological and virological data for the Northern and Southern Hemispheres over several consecutive seasons. It focuses exclusively on severe cases of influenza requiring hospitalization. A standard protocol is shared between sites allowing comparison and pooling of results. During the 2014-2015 influenza season, the GIHSN included seven coordinating sites from six countries (St. Petersburg and Moscow, Russian Federation; Prague, Czech Republic; Istanbul, Turkey; Beijing, China; Valencia, Spain; and Rio de Janeiro, Brazil). Here, we present the detailed epidemiological and influenza vaccine effectiveness findings for the Northern Hemisphere 2014-2015 influenza season. PMID- 27556805 TI - Read-Split-Run: an improved bioinformatics pipeline for identification of genome wide non-canonical spliced regions using RNA-Seq data. AB - BACKGROUND: Most existing tools for detecting next-generation sequencing-based splicing events focus on generic splicing events. Consequently, special types of non-canonical splicing events of short mRNA regions (IRE1alpha targeted) have not yet been thoroughly addressed at a genome-wide level using bioinformatics approaches in conjunction with next-generation technologies. During endoplasmic reticulum (ER) stress, the gene encoding the RNase Ire1alpha is known to splice out a short 26 nt region from the mRNA of the transcription factor Xbp1 non canonically within the cytosol. This causes an open reading frame-shift that induces expression of many downstream genes in reaction to ER stress as part of the unfolded protein response (UPR). We previously published an algorithm termed "Read-Split-Walk" (RSW) to identify non-canonical splicing regions using RNA-Seq data and applied it to ER stress-induced Ire1alpha heterozygote and knockout mouse embryonic fibroblast cell lines. In this study, we have developed an improved algorithm "Read-Split-Run" (RSR) for detecting genome-wide Ire1alpha targeted genes with non-canonical spliced regions at a faster speed. We applied the RSR algorithm using different combinations of several parameters to the previously RSW tested mouse embryonic fibroblast cells (MEF) and the human Encyclopedia of DNA Elements (ENCODE) RNA-Seq data. We also compared the performance of RSR with two other alternative splicing events identification tools (TopHat (Trapnell et al., Bioinformatics 25:1105-1111, 2009) and Alt Event Finder (Zhou et al., BMC Genomics 13:S10, 2012)) utilizing the context of the spliced Xbp1 mRNA as a positive control in the data sets we identified it to be the top cleavage target present in Ire1alpha (+/-) but absent in Ire1alpha (-/-) MEF samples and this comparison was also extended to human ENCODE RNA-Seq data. RESULTS: Proof of principle came in our results by the fact that the 26 nt non conventional splice site in Xbp1 was detected as the top hit by our new RSR algorithm in heterozygote (Het) samples from both Thapsigargin (Tg) and Dithiothreitol (Dtt) treated experiments but absent in the negative control Ire1alpha knock-out (KO) samples. Applying different combinations of parameters to the mouse MEF RNA-Seq data, we suggest a General Linear Model (GLM) for both Tg and Dtt treated experiments. We also ran RSR for a human ENCODE RNA-Seq dataset and identified 32,597 spliced regions for regular chromosomes. TopHat (Trapnell et al., Bioinformatics 25:1105-1111, 2009) and Alt Event Finder (Zhou et al., BMC Genomics 13:S10, 2012) identified 237,155 spliced junctions and 9,129 exon skipping events (excluding chr14), respectively. Our Read-Split-Run algorithm also outperformed others in the context of ranking Xbp1 gene as the top cleavage target present in Ire1alpha (+/-) but absent in Ire1alpha (-/-) MEF samples. The RSR package including source codes is available at http://bioinf1.indstate.edu/RSR and its pipeline source codes are also freely available at https://github.com/xuric/read-split-run for academic use. CONCLUSIONS: Our new RSR algorithm has the capability of processing massive amounts of human ENCODE RNA-Seq data for identifying novel splice junction sites at a genome-wide level in a much more efficient manner when compared to the previous RSW algorithm. Our proposed model can also predict the number of spliced regions under any combinations of parameters. Our pipeline can detect novel spliced sites for other species using RNA-Seq data generated under similar conditions. PMID- 27556806 TI - Correlation of Quantitative Motor State Assessment Using a Kinetograph and Patient Diaries in Advanced PD: Data from an Observational Study. AB - INTRODUCTION: Effective management and development of new treatment strategies for response fluctuations in advanced Parkinson's disease (PD) largely depends on clinical rating instruments such as the PD home diary. The Parkinson's kinetigraph (PKG) measures movement accelerations and analyzes the spectral power of the low frequencies of the accelerometer data. New algorithms convert each hour of continuous PKG data into one of the three motor categories used in the PD home diary, namely motor Off state and On state with and without dyskinesia. OBJECTIVE: To compare quantitative motor state assessment in fluctuating PD patients using the PKG with motor state ratings from PD home diaries. METHODS: Observational cohort study on 24 in-patients with documented motor fluctuations who completed diaries by rating motor Off, On without dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were analyzed and calibrated to the patient's individual thresholds for Off and dyskinetic state by novel algorithms classifying the continuous accelerometer data into these motor states for every hour between 6 am and 10 pm. RESULTS: From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state time were excluded from analyses). Distributions of total motor state hours per day measured by PKG showed moderate-to-strong correlation to those assessed by diaries for the different motor states (Pearson's correlations coefficients: 0.404-0.658), but inter-rating method agreements on the single-hour-level were only low-to-moderate (Cohen's kappa: 0.215-0.324). CONCLUSION: The PKG has been shown to capture motor fluctuations in patients with advanced PD. The limited correlation of hour-to hour diary and PKG recordings should be addressed in further studies. PMID- 27556807 TI - Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013. AB - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. METHODOLOGY/PRINCIPAL FINDINGS: After a cluster of pediatric dengue-associated HLH patients was identified during the 2012-2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008-2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012-2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p <= 0.02). CONCLUSIONS/SIGNIFICANCE: During this cluster of dengue-associated HLH cases that was temporally associated with the 2012-2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury. PMID- 27556808 TI - Comparison of Electric- and Magnetic-Cardiograms Produced by Myocardial Ischemia in Models of the Human Ventricle and Torso. AB - Myocardial ventricular ischemia arises from a lack of blood supply to the heart, which may cause abnormal repolarization and excitation wave conduction patterns in the tissue, leading to cardiac arrhythmias and even sudden death. Current diagnosis of cardiac ischemia by the 12-lead electrocardiogram (ECG) has limitations as they are insensitive in many cases and may show unnoticeable differences to normal patterns. As the magnetic field provides extra information on cardiac excitation and is more sensitive to tangential currents to the surface of the chest, whereas the electric field is more sensitive to flux currents, it has been hypothesized that the magnetocardiogram (MCG) may provide a complementary method to the ECG in ischemic diagnosis. However, it is unclear yet about the differences in sensitivity regions of body surface ECG and MCG signals to ischemic conditions. The aim of this study was to investigate such differences by using 12-, 36- ECG and 36-MCG computed from multi-scale biophysically detailed computational models of the human ventricles and torso in both control and ischemic conditions. It was shown that ischemia produced changes in the ECG and MCG signals in the QRS complex, T-wave and ST-segment, with greater relative differences seen in the 36-lead ECG and MCG as compared to the 12-leads ECG (34% and 37% vs 26%, respectively). The 36-lead ECG showed more averaged sensitivity than the MCG in the change of T-wave due to ischemia (37% vs 32%, respectively), whereas the MCG showed greater sensitivity than the ECG in the change of the ST segment (50% vs 40%, respectively). In addition, both MCG and ECG showed regional dependent changes to ischemia, but with MCG showing a stronger correlation between ischemic region in the heart. In conclusion, MCG shows more sensitivity than ECG in response to ischemia, which may provide an alternative method for the diagnosis of ischemia. PMID- 27556809 TI - FDG-PET/CT Limited to the Thorax and Upper Abdomen for Staging and Management of Lung Cancer. AB - PURPOSE: This study evaluates the diagnostic accuracy of [F-18] fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) of the chest/upper abdomen compared to the generally performed scan from head to upper thighs, for staging and management of (suspected) lung cancer in patients with no history of malignancy or complaints outside the thorax. METHODS: FDG PET/CT scans of 1059 patients with suspected or recently proven lung cancer, with no history of malignancy or complaints outside the thorax, were analysed in a retrospective multi-centre trial. Suspect FDG-avid lesions in the chest and upper abdomen, the head and neck area above the shoulder line and in the abdomen and pelvis below the caudal tip of the liver were noted. The impact of lesions detected in the head and neck area and abdomen and pelvis on additional diagnostic procedures, staging and treatment decisions was evaluated. RESULTS: The head and neck area revealed additional suspect lesions in 7.2%, and the abdomen and pelvis in 15.8% of patients. Imaging of the head and neck area and the abdomen and pelvic area showed additional lesions in 19.5%, inducing additional diagnostic procedures in 7.8%. This resulted in discovery of additional lesions considered malignant in 10.7%, changing patient management for lung cancer in 1.2%. In (suspected) lung cancer, PET/CT limited to the chest and upper abdomen resulted in correct staging in 98.7% of patients, which led to the identical management as full field of view PET in 98.8% of patients. CONCLUSION: High value of FDG-PET/CT for staging and correct patient management is already achieved with chest and upper abdomen. Findings in head and neck area and abdomen and pelvis generally induce investigations with limited or no impact on staging and treatment of NSCLC, and can be interpreted accordingly. PMID- 27556811 TI - Circular Dichroism of Electric-Field-Oriented CdSe/CdS Quantum Dots-in-Rods. AB - Here we report anisotropy of intrinsic chiroptical response in CdSe/CdS quantum dot-in-rod systems. These nanostructures being oriented in an external electric field demonstrate dependence of circular dichroism signal on the orientation of the nanocrystals. The type of circular polarization in these nanostructures correlates with preferential direction of linear polarization, and the degree of circular polarization is the maximal for the first circular dichroism band corresponding to the absorption band edge. We also support our experimental data with a theoretical model. Using this model, we show a direct connection between theoretically derived morphological parameters of twisting in nanocrystals lattices and calculated from experimental data parameters of circular dichroism anisotropy. PMID- 27556810 TI - Biophysical and Pharmacological Characterization of Nav1.9 Voltage Dependent Sodium Channels Stably Expressed in HEK-293 Cells. AB - The voltage dependent sodium channel Nav1.9, is expressed preferentially in peripheral sensory neurons and has been linked to human genetic pain disorders, which makes it target of interest for the development of new pain therapeutics. However, characterization of Nav1.9 pharmacology has been limited due in part to the historical difficulty of functionally expressing recombinant channels. Here we report the successful generation and characterization of human, mouse and rat Nav1.9 stably expressed in human HEK-293 cells. These cells exhibit slowly activating and inactivating inward sodium channel currents that have characteristics of native Nav1.9. Optimal functional expression was achieved by coexpression of Nav1.9 with beta1/beta2 subunits. While recombinantly expressed Nav1.9 was found to be sensitive to sodium channel inhibitors TC-N 1752 and tetracaine, potency was up to 100-fold less than reported for other Nav channel subtypes despite evidence to support an interaction with the canonical local anesthetic (LA) binding region on Domain 4 S6. Nav1.9 Domain 2 S6 pore domain contains a unique lysine residue (K799) which is predicted to be spatially near the local anesthetic interaction site. Mutation of this residue to the consensus asparagine (K799N) resulted in an increase in potency for tetracaine, but a decrease for TC-N 1752, suggesting that this residue can influence interaction of inhibitors with the Nav1.9 pore. In summary, we have shown that stable functional expression of Nav1.9 in the widely used HEK-293 cells is possible, which opens up opportunities to better understand channel properties and may potentially aid identification of novel Nav1.9 based pharmacotherapies. PMID- 27556812 TI - Merging Visible Light Photoredox Catalysis with Metal Catalyzed C-H Activations: On the Role of Oxygen and Superoxide Ions as Oxidants. AB - The development of efficient catalytic systems for direct aromatic C-H bond functionalization is a long-desired goal of chemists, because these protocols provide environmental friendly and waste-reducing alternatives to classical methodologies for C-C and C-heteroatom bond formation. A key challenge for these transformations is the reoxidation of the in situ generated metal hydride or low valent metal complexes of the primary catalytic bond forming cycle. To complete the catalytic cycle and to regenerate the C-H activation catalyst, (super)stoichiometric amounts of Cu(II) or Ag(I) salts have often been applied. Recently, "greener" approaches have been developed by applying molecular oxygen in combination with Cu(II) salts, internal oxidants that are cleaved during the reaction, or solvents or additives enabling the metal hydride reoxidation. All these approaches improved the environmental friendliness but have not overcome the obstacles associated with the overall limited functional group and substrate tolerance. Hence, catalytic processes that do not feature the unfavorable aspects described above and provide products in a streamlined as well as economically and ecologically advantageous manner would be desirable. In this context, we decided to examine visible light photoredox catalysis as a new alternative to conventionally applied regeneration/oxidation procedures. This Account summarizes our recent advances in this expanding area and will highlight the new concept of merging distinct redox catalytic processes for C-H functionalizations through the application of visible light photoredox catalysis. Photoredox catalysis can be considered as catalytic electron-donating or -accepting processes, making use of visible-light absorbing homogeneous and heterogeneous metal-based catalysts, as well as organic dye sensitizers or polymers. As a consequence, photoredox catalysis is, in principle, an ideal tool for the recycling of any given metal catalyst via a coupled electron transfer (ET) process. Here we describe our first successful endeavors to address the above challenges by combining visible light photoredox catalysis with different ruthenium, rhodium, or palladium catalyzed C H activations. Since only small amounts of the oxidant are generated and are immediately consumed in these transformations, side reactions of substrates or products can be avoided. Thus, usually oxidant-sensible substrates can be used, which makes these methods highly suitable for complex molecular structure syntheses. Moreover, mechanistic studies shed light on new reaction pathways, intermediates, and in situ generated species. The successful development of our dual catalysis concept, consisting of combined visible light photoredox catalysis and metal catalyzed C-H functionalization, provides many new opportunities for further explorations in the field of C-H functionalization. PMID- 27556813 TI - Characterization of a scintillating fibre detector for small animal imaging and irradiation dosimetry. AB - OBJECTIVE: Small animal image-guided irradiators have recently been developed to mimic the delivery techniques of clinical radiotherapy. A dosemeter adapted to millimetric beams of medium-energy X-rays is then required. This work presents the characterization of a dosemeter prototype for this particular application. METHODS: A scintillating optical fibre dosemeter (called DosiRat) has been implemented to perform real-time dose measurements with the dedicated small animal X-RAD(r) 225Cx (Precision X-Ray, Inc., North Branford, CT) irradiator. Its sensitivity, stem effect, stability, linearity and measurement precision were determined in large field conditions for three different beam qualities, consistent with small animal irradiation and imaging parameters. RESULTS: DosiRat demonstrates good sensitivity and stability; excellent air kerma and air kerma rate linearity; and a good repeatability for air kerma rates >1 mGy s-1. The stem effect was found to be negligible. DosiRat showed limited precision for low air kerma rate measurements (<1 mGy s-1), typically for imaging protocols. A positive energy dependence was found that can be accounted for by calibrating the dosemeter at the needed beam qualities. CONCLUSION: The dosimetric performances of DosiRat are very promising. Extensive studies of DosiRat energy dependence are still required. Further developments will allow to reduce the dosemeter size to ensure millimetric beams dosimetry and perform small animal in vivo dosimetry. Advances in knowledge: Among existing point dosemeters, very few are dedicated to both medium-energy X-rays and millimetric beams. Our work demonstrated that scintillating fibre dosemeters are suitable and promising tools for real-time dose measurements in the small animal field of interest. PMID- 27556814 TI - Nursing Strategies to Increase Medication Safety in Inpatient Settings. PMID- 27556815 TI - Phenylpyrrole-based HDAC inhibitors: synthesis, molecular modeling and biological studies. AB - AIM: Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in the initiation and progression of cancer. Currently, three hydroxamate-containing HDAC pan-inhibitors have been approved as antitumor agents. RESULTS: We herein present the development of a series of novel phenylpyrrole-based derivatives stemmed from combined computational and medicinal chemistry efforts to rationally modulate HDAC1/6 isoform selectivity. In vitro activity on HDAC1 and HDAC6 isoforms and the effects of selected analogs on histone H3 and alpha-tubulin acetylation levels were determined. Cell-based data evidenced, for selected compounds, a promising antitumor potential and low toxicity on normal cells. CONCLUSION: The newly developed compounds represent a valuable starting point for the development of novel anticancer agents. PMID- 27556816 TI - Immune effect and safety evaluation of vaccine prepared by dendritic cells modified by rAAV-carrying BCSG1 gene. AB - The immune effect and safety evaluation of rAAV (recombinant adeno-associated virus)-containing Bcsg1 (breast cancer-specific gene 1) (rAAV/Bcsg1)-transfected DC (dendritic cell) (rAAV/Bcsg1-DC) vaccine in immunotherapy for (BCSG1) (+) BC was assessed. Immune effect of cytotoxic T lymphocytes (CTLs) on Bcsg1 (+) BC cells, and rAAV gene residuals in mature CTL cells and culture medium were determined. Nude mouse xenograft tumor model was established to assess the inhibition effects of DC-activated CTLs on tumor growth. DC cell surface markers were highly expressed in rAAV/Bcsg1 group and lysate-DC group, and rAAV/Bcsg1-DC CTL showed stronger cytotoxic activity targeting Bcsg1 (+) BC cells. The rAAV/Bcsg1-DC vaccine-treated groups showed lower mean tumor weight, higher tumor inhibition rates and slower tumor growth. rAAV/Bcsg1-DC can induce highly efficient CTL-targeting Bcsg1 antigen without rAAV gene residuals. PMID- 27556818 TI - Amnioinfusion for chorioamnionitis. AB - BACKGROUND: Chorioamnionitis is a leading cause of perinatal morbidity and mortality. Amnioinfusion aims at reducing the adverse effects of chorioamnionitis by dilution of the infective organisms or by an anti-microbial effect of the fluid infused. OBJECTIVES: The objective of this review was to determine the effect of amnioinfusion on clinical and sub-clinical chorioamnionitis, fetal well being, fetal heart rate characteristics and perinatal and maternal morbidity and mortality. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 July 2016), PubMed, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised clinical trials (RCTs) of amnioinfusion (treatment group) versus no amnioinfusion in women with chorioamnionitis.We would have also considered trials comparing amnioinfusion with sham amnioinfusion; different types or volumes of amnioinfusion fluid but none were identified.Cluster-RCTs and quasi-RCTs were eligible for inclusion but none were identified. We identified one study published in abstract form but it did not contain any numerical data and has therefore been excluded. Studies using a cross-over design are not an appropriate study design and thus were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed potential studies for inclusion and assessed trial quality. Both review authors independently extracted data and data were checked for accuracy. MAIN RESULTS: We included one small trial (with data from 34 participants) comparing transcervical amnioinfusion with no amnioinfusion. The trial was considered to be at a high risk of bias overall, due to small numbers, inconsistency in the reporting and lack of information on blinding. Meta-analysis was not possible. Transcervical amnioinfusion was with room temperature saline at 10 mL per minute for 60 minutes, then 3 mL per minute until delivery versus no amnioinfusion. All women received intrauterine pressure catheter, acetaminophen and antibiotics (ampicillin or, if receiving Group B beta streptococcal prophylaxis, penicillin and gentamycin). We did not identify any trials that used transabdominal amnioinfusion.Compared to no amnioinfusion, transcervical amnioinfusion had no clear effect on the incidence of postpartum endometritis (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.29 to 7.87; absolute risk 176/1000 (95% CI 34 to 96) versus 118/1000;low-quality evidence). Nor was there a clear effect in the incidence of neonatal infection (RR 3.00, 95% CI 0.13 to 68.84; absolute risk 0/1000 (95% CI 0 to 0) versus 0/1000; low-quality evidence). The outcome of perinatal death or severe morbidity (such as neonatal encephalopathy, intraventricular haemorrhage, admission to intensive/high care) was not reported in the included trial.In terms of this review's secondary outcomes, the rate of caesarean section was the same in both groups (RR 1.00, 95% CI 0.35 to 2.83; absolute risk 294/1000 (95% CI 103 to 832) versus 294/1000; low-quality evidence). There was no clear difference in the duration of maternal antibiotic treatment between the amnioinfusion and no amnioinfusion control group (mean difference (MD) 16 hours, 95% CI -1.75 to 33.75); nor in the duration of hospitalisation (MD 3.00 hours, 95% CI -15.49 to 21.49). The study did not report any information about how many babies had a low Apgar score at five minutes after birth.Women in the amnioinfusion group had a lower temperature at delivery compared to women in the control group (MD -0.38 degrees C, 95% CI -0.74 to 0.02) but this outcome was not pre-specified in the protocol for this review.The majority of this review's secondary outcomes were not reported in the included study. AUTHORS' CONCLUSIONS: There is insufficient evidence to fully evaluate the effectiveness of using transcervical amnioinfusion for chorioamnionitis and to assess the safety of this intervention or women's satisfaction. We did not identify any trials that used transabdominal amnioinfusion. The evidence in this review can neither support nor refute the use of transcervical amnioinfusion outside of clinical trials. We included one small study that reported on a limited number of outcomes of interest in this review. The numbers included in this review are too small for meaningful assessment of substantive outcomes, where reported. For those outcomes we assessed using GRADE (postpartum endometritis, neonatal infection, and caesarean section), we downgraded the quality of the evidence to low - with downgrading decisions based on small numbers and a lack of information on blinding. The included study did not report on this review's other primary outcome (perinatal death or severe morbidity).The reduction in pyrexia, though not a pre-specified outcome of this review, may be of relevance in terms of benefits to the fetus of reduced exposure to heat. We postulate that the temperature reduction found may be a direct cooling effect of amnioinfusion with room temperature fluid, rather than reduction of infection. Larger trials are needed to confirm and extend the findings of the trial reviewed here. These should be randomised controlled trials; participants, women with chorioamnionitis; interventions, amnioinfusion; comparisons, no amnioinfusion; outcomes, maternal and perinatal outcomes including neurodevelopmental measures.Further research is justified to determine possible benefits or risks of amnioinfusion for chorioamnionitis, and to investigate possible benefits of reducing temperature in fetuses considered at risk of neurological damage. Research should include randomised trials to examine transcervical or transabdominal amnioinfusion compared with no infusion for chorioamnionitis and examine outcomes listed in the methods of this review. PMID- 27556817 TI - Hepatocyte growth factor-modified mesenchymal stem cells improve ischemia/reperfusion-induced acute lung injury in rats. AB - Accumulative evidence demonstrated that mesenchymal stem cell (MSC) engraftment could protect tissue injury from ischemia/reperfusion (I/R). Hepatocyte growth factor (HGF) has important roles in the cell and tissue repairment and regeneration. Here we investigated the enhanced effects of HGF-modified MSCs on I/R-induced acute lung injury. Rat bone marrow-derived MSCs were successfully transfected to express HGF. HGF modification did not affect the characteristics of MSCs, and increased MSC viability, and inhibit the proinflammatory phenotype of MSCs in the inflammatory condition. In the rat model of I/R-induced lung injury, MSC-HGF engraftment attenuated lung wet-to-dry weight ratio, enhanced PaO2 level and improved lung pathological injury, compared with MSC treatment. Moreover, the decreased acitivity of malondialdehyde, myeloperoxidase and tumor necrosis factor-alpha and increased superoxide dismutase content and interleukin 10 level were also observed in the MSC-HGF treatment, compared with the MSC group. Importantly, we found that HGF contributed to the survival of engrafted MSCs in the lung tissue through upregulation of Bcl-2 level and reduction of Caspase 3 activation. Thus our data show for the first time a clear beneficial effect of HGF gene modification on the survival of MSCs and enhanced improvement for I/R-induced lung injury. PMID- 27556819 TI - Laryngeal Squamous Cell Carcinomas are Commonly Associated With Differentiated Squamous Intraepithelial Neoplasia With or Without an Admixture With Usual Type of Squamous Intraepithelial Neoplasia: Clinical and Pathologic Significance. AB - BACKGROUND: Differentiated squamous intraepithelial neoplasia (dSIN) is a pathway in the development of invasive squamous cell carcinoma (SCC) distinct from the usual-type squamous intraepithelial neoplasia (uSIN) and has not been described in the larynx. MATERIALS AND METHODS: Sixty-nine consecutive cases of SCC were identified which included 25 dSIN, 13 uSIN, and 31 mixed dSIN+usual-like SIN (u like SIN) cases. RESULTS: dSIN was characterized by atypical squamous cells limited to the basal/parabasal layers and u-like SIN was characterized by cytologic atypia limited to less than full thickness. Despite the lack of neoplastic involvement of the full thickness of the epithelium, these types of SIN were commonly connected with invasive carcinoma. Prior biopsies demonstrating only dSIN, without the underlying invasive SCC, were underdiagnosed in 2 cases. Because of the frequent keratinization, u-like SIN likely represents the "keratinized dysplasia" and shows changes suggestive of dSIN with upward spread of neoplastic cells into the upper layer of the epithelium. CONCLUSIONS: Laryngeal dSIN represents an important but under recognized pathway of invasive SCC development. As moderate dysplasia of uSIN type are not associated with invasive SCC, labeling u-like SIN as dysplasia of grade 2 or 3 likely leads to the controversies in the current grading systems in the upper aerodigestive system and causes confusion for clinicians. PMID- 27556820 TI - High Expression of Vimentin is Associated With Progression and a Poor Outcome in Glioblastoma. AB - Glioblastoma multiforme (GBM) has a high recurrence and mortality rate. Because of a poor understanding of the mechanism for this disease, treatment regimens have remained limited. Vimentin, one of the major cytoskeletal proteins, is associated with cellular structure. However, the function of vimentin in GBM is still undefined. In the present study, we investigated the expression level of vimentin in 179 GBM tissues using immunohistochemistry. We found that the vimentin expression level was associated with the time to progression (P=0.029). A Kaplan-Meier analysis revealed that patients with high vimentin expression had a significantly shorter overall survival (P=0.0002) and progression-free survival (P=0.0001) compared with those with low expression. Furthermore, in vitro experiments showed that withaferin-A, a chemical inhibitor of vimentin, could inhibit GBM cell migration and invasion activity when its concentrations were <0.5 MUM, and higher concentrations of withaferin-A could decrease the viability of U251and U87 cells significantly. In conclusion, our results indicated that vimentin may play an important role in the progression of GBM. PMID- 27556821 TI - The Evaluation of Angiogenesis Markers in Hepatocellular Carcinoma and Precursor Lesions in Liver Explants From a Single Institution. AB - Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. Precursor lesions are described, and the correct diagnosis of liver nodules is paramount when considering liver transplantation. We evaluated the immunohistochemical expression of vascular endothelial growth factor (VEGF) and angiopoietin-2 in HCC and precursors lesion in a single institution series of whole liver explants between 2013 and 2015, evaluating morphologic and clinical variables. The study comprised 67 patients (32.8% female) and 107 nodules. The mean age of the patients was 52.7 years (29 to 70 y). There were no significant epidemiologic differences among malignant lesions, dysplastic nodules, and regenerative nodules. Angiopoietin-2 expression was significantly more expressed in carcinoma when compared with regenerative lesions (P<0.0001). A statistically significant relationship was noted between the expression of VEGF in hepatocytes and Ang-2 expression in the small vasculature (P=0.006). VEGF expression also correlated significantly with the number of nonpaired arteries (P=0.03), although it was not useful in separating benign from malignant cases. We identified a sensitivity of 54% and a specificity of 96% using angiopoietin-2, and a sensitivity of 68.7% and a specificity of 31.2% when using VEGF for the diagnosis of HCC. There was no significant correlation between the immunohistochemical parameters and the clinical staging, the number of gross lesions, and the histologic grade in cases of HCC. Angiopoietin-2 may be a candidate biomarker in assessing liver nodules in transplant patients, and may assist in the diagnosis of difficult lesions and in small biopsies pretransplant. PMID- 27556822 TI - Succinate Dehydrogenase B (SDHB) Immunohistochemistry for the Evaluation of Muscle Biopsies. AB - Succinate dehydrogenase (SDH) is a key mitochondrial enzyme complex composed of 4 subunits. SDH histochemistry is routinely utilized in the assessment of muscle biopsies to reveal underlying pathology such as subsarcolemmal mitochondrial aggregates. In this study, we evaluated the utility of succinate dehydrogenase B (SDHB) immunohistochemistry (IHC) in 27 muscle biopsies, including 13 mitochondrial myopathies (MMs), 9 inflammatory myopathies, and 5 controls. SDHB IHC was performed on formalin-fixed, paraffin-embedded tissue sections with a mouse monoclonal antibody (Abcam 21A11AE7) in parallel with histochemical SDH stains on a fresh-frozen tissue. In all muscle biopsies, SDHB IHC exhibited granular immunoreactivity and highlighted the dark type 1 and lighter type 2 staining pattern observed by histochemistry. In all cases of MM, SDHB IHC showed subsarcolemmal granular aggregates involving the entire periphery of the fibers that were more distinct than those seen by SDH histochemistry. In 3 extraocular muscle biopsies, SDHB immunoreactive speckles of various sizes were distributed throughout the entire sarcoplasm that were more prominent than those seen on SDH histochemistry. Subsarcolemmal and cytoplasmic granular aggregates seen on SDHB IHC correlated with mitochondrial pathology on electron microscopy. In cases of inflammatory myopathy, there was diffuse sarcoplasmic SDHB immunoreactivity in degenerating fibers, but no evidence of subsarcolemmal aggregates. This study demonstrates that SDHB IHC is highly sensitive and specific in the identification of MM. The automation, reproducibility, and cost efficiency of SDHB IHC offer advantages over the labor-intensive histochemical method requiring frozen sections. As this technique is performed on formalin-fixed, paraffin-embedded tissues, it can be easily applied for retrospective studies. PMID- 27556823 TI - Proximal CD13 Versus Distal GATA-3 Expression in Renal Neoplasia According to WHO 2016 Classification. AB - Little is known about the aminopeptidase CD13 in renal neoplasia according to the new 2016 World Health Organization renal tumor classification. We selected 175 cases, including 79 clear cell, 31 papillary, 24 chromophobe, 8 clear cell papillary renal cell carcinomas (RCCs), 21 oncoytomas, and 12 microphthalmia transcription factor family translocation RCCs: 4 t(6;11)/transcription factor EB (TFEB), 7 t(Xp11) with 2 cystic variants and 1 t(X;17). GATA binding protein 3 (GATA-3) was inserted as control. Expression of proximal antigen CD13 was observed in 63/79 (80%) clear cell, 25/31 (81%) papillary, 3/8 (37%) clear cell papillary, 1/4 (25%) t(6;11)/TFEB, 2/7 (28%) cystic t(Xp11), and in 1/1 t(X;17) RCCs. All chromophobe RCC (0/24) and all oncocytomas (0/21) resulted negative. CD10 was seen in 76/79 (96%) clear cell, 15/31 (48%) papillary, 10/24 (42%) chromophobe, 1/8 (12%) clear cell papillary RCCs, 4/21 (19%) oncocytomas, 1/4 (25%) t(6;11)/TFEB, 2/7 (29%) cystic t(Xp11), and in 1/1 t(X;17) RCCs. GATA-3 was positive in 3/7 (42%) clear cell papillary RCCs and negative in all remaining RCCs, except a single chromophobe RCC and a single oncocytoma. We concluded that: (1) CD13 and GATA-3 immunostains may serve as a diagnostic aid in differentiating subtypes of RCC; (2) CD13 is always absent in chromophobe RCC and oncocytomas, whereas CD10 can be immunoexpressed in both; (3) CD13 should be included in a panel of antibodies to distinguish "proximal renal tumors" from "distal renal tumors" and between clear cell RCC versus microphthalmia transcription factor family translocations RCCs; and (4) when present, GATA-3 is specific for clear cell papillary RCC. PMID- 27556824 TI - Relationship between electrical activity of the temporal and masseter muscles, bite force, and morphological facial index. AB - PURPOSE: To analyze possible correlations between the electrical activity of masseter and temporal muscles, Bite Force (BF), and Morphological Facial Indices (MFI). METHODS: The study involved 43 young adults, both genders, 18 to 37 years old. The individuals were submitted to: face measurement to calculate MFI; Masseter and Temporal Surface Electromyography (sEMG) and BF measurements on right and left premolars and incisors. The following electromyographic tests were conducted: at rest position; Maximal Voluntary Isometrical Contraction (MVIC) and usual chewing of raisins. Statistical analysis was conducted using the coefficient of Spearman correlation with significance level of 5%. RESULTS: The values at rest in the temporal muscles were significantly higher than those in the masseter muscles. A meaningful correlation was found between MFI and sEMG in the MVIC test for the Left Temporal (rs=36, p=0.017). A significant correlation was observed between FMI and sEMG during BF in incisors for temporal muscles and the Right Masseter. During the force tests, it was possible to observe a meaningful correlation between BF in right premolars and the sEMG of the Left Temporal and Masseters. CONCLUSION: No correlation was found between the sEMG of temporal and masseter muscles, BF, and FMI in adult individuals based on the tests performed. The SEMG of temporal and masseter muscles seems to be associated only with BF. As a datum of habitual postural characteristic, the electrical activity of temporal muscles is higher than the activity of masseters, also regardless of MFI. PMID- 27556825 TI - Posture and body balance of schoolchildren aged 8 to 12 years with and without oral breathing. AB - PURPOSE: This study aims to evaluate the posture and body balance of students with and without oral breathing, as well as to verify whether there is a correlation between the values obtained in this evaluation and those of the analysis of sensory systems. METHODS: The research was conducted with school children aged 8 to 12 years. The sample was subdivided into two study groups: schoolchildren with oral breathing and school children without oral breathing (control). The division of the groups was determined on the basis of pre established criteria investigated in the anamnesis, hearing evaluation, and assessment of the stomatognathic system. The schoolchildren from both groups were submitted to postural evaluation using the Postural Assessment Software (SAPO) on the right and left lateral views and the Foam-laser Dynamic Posturography test. RESULTS: In the assessment of posture, a statistically significant difference was found only in the knee angle on the left lateral view. With regards to the Dynamic Posturography, there was a statistically significant difference in the values obtained in the six tests of sensory organization (TOS). There was a moderate correlation between the position of the head on the left lateral view and the sensory systems. CONCLUSIONS: Schoolchildren with oral breathing present postural changes compared with those without oral breathing, mainly regarding the positioning of the knee. The body balance in the group of schoolchildren with oral breathing showed greater impairment compared with that in the group of schoolchildren without oral breathing. There is a correlation between the cephalic position and the different sensory systems. PMID- 27556826 TI - SUS users' perception: a speech-language pathology approach based on health promotion. AB - PURPOSE: This study aimed to analyze the perceptions of users of the Brazilian Unified Health System (SUS) about the treatment Center where they were assisted, as well as about the speech-language pathology services rendered by this Center. METHODS: This is a transversal study composed of an interview with 26 open questions and 14 closed questions applied to 111 individuals who were assisted at the SUS Center in August 2013. The quantitative content analysis was conducted through the use of the GraphPadPrisma 5.1, Statistic Package for Social Sciences (SPSS) 15.0 software and the application of the D'agostino & Person, F-test and chi-squared test. RESULTS: Most participants reported a positive perception about the facilities and staff of the treatment center. They were also positive about the waiting time and the speech-language pathologists' explanations and conduct, especially in the audiology department. Most responses from participants were short and did not present an argumentative context. CONCLUSION: The treatment center received a high approval rating by most users. The audiology department had better grades than the clinical services related to language and oral motor pathologies. PMID- 27556827 TI - Aspects of oral communication in patients with Parkinson's disease submitted to Deep Brain Stimulation. AB - INTRODUCTION: Deep Brain Stimulation (DBS) has been satisfactorily used to control the cardinal motor symptoms of Parkinson's disease (PD), but little is known about its impact on communication. PURPOSE: This study aimed to characterize the aspects of cognition, language, speech, voice, and self perception in two patients with PD, pre- and post- DBS implant surgery. METHODS: The patients were assessed using a cognitive screening test, a brief language evaluation, a self-declared protocol, and an analysis of the aspects of voice and speech, which was conducted by a specialized Speech-language Therapist who was blinded for the study. RESULTS: At the pre-surgery assessment, Case I showed impairment regarding the aspects of cognition, language and voice, whereas Case II showed impairment only with respect to the voice aspect. The post-surgery evaluation of the cases showed an opposite pattern of the effect of DBS after analysis of the communication data: Case I, who presented greater impairment before the surgery, showed improvement in some aspects; Case II, who presented lower communicative impairment before the surgery, showed worsening in other aspects. CONCLUSION: This study shows that DBS may influence different communication aspects both positively and negatively. Factors associated with the different effects caused by DBS on the communication of patients with PD need to be further investigated. PMID- 27556828 TI - Receptive and expressive language performance in children with and without Cleft Lip and Palate. AB - PURPOSE: To compare the performance in the abilities of receptive and expressive language of children with cleft lip and palate with that of children without cleft lip and palate with typical 12 to 36-month chronological development. METHOD: The sample consisted of 60 children aged 12 and 36 months: 30 with cleft lip and palate diagnosis and 30 without cleft lip and palate diagnosis with typical development. The groups were paired according to gender, age (in months), and socioeconomic level. The procedures consisted of analysis of medical records, anamnesis with family members, and valuation of the Early Language Milestone Scale (ELMS). The chart analysis showed 63.34% of the children with unilateral cleft lip and palate, 16.66% with bilateral incisive transforamen cleft, and 20% with post-foramen cleft. Children with cleft lip and palate underwent surgeries (lip repair and/or palatoplasty) at the recommended ages and participated in early intervention programs; 40% presented recurrent otitis history, and 50% attended schools. Statistical analysis included the use of the Mann Whitney test with significance level of p <0.05. RESULTS: There was a statistically significant difference between the groups regarding receptive and expressive skills. CONCLUSION: The group of children with cleft lip and palate showed statistically significant low performance in receptive and expressive language compared with children without cleft lip and palate. PMID- 27556829 TI - Association of Part D coverage gap with COPD medication adherence. AB - OBJECTIVES: This study assessed the association of the Medicare Part D coverage gap with medication adherence among beneficiaries with chronic obstructive pulmonary disease (COPD). STUDY DESIGN: Retrospective observational study based on Medicare claims data. METHODS: A 5% random sample of Medicare claims data (2006-2010) was used in this study. Beneficiaries diagnosed with COPD and treated with long-acting bronchodilators (LABDs) were assigned to an exposure cohort (at risk of the coverage gap) or a control cohort (otherwise). The exposure and control cohorts were matched using high-dimensional propensity scores. Adherence was defined as >=80% of the proportion of days covered by LABDs. Logistic regressions controlling for unbalanced covariates post matching were applied to assess the association of the coverage gap with adherence. RESULTS: The final matched exposure and control cohorts each included 4147 patient-year observations with about 42% and 46% of them adherent to LABDs, respectively. About 17% of the exposure cohort hit the coverage gap after October 31. Logistic regression showed that, compared with the control cohort, the beneficiaries in the exposure cohort had a significantly lower likelihood of being adherent if they hit the coverage gap later in the year (odds ratio [OR], 0.603; 95% CI, 0.493-0.738), or had a lower likelihood without statistical significance if otherwise (OR, 0.931; 95% CI, 0.846-1.024). CONCLUSIONS: The findings suggest that the Part D coverage gap was associated with lower adherence in patients with COPD, which may serve as evidentiary support for phasing out the coverage gap by 2020. PMID- 27556830 TI - The financial impact of team-based care on primary care. AB - OBJECTIVES: Although team-based care can improve coronary heart disease (CHD) risk factors and is considered cost-effective from a healthcare system perspective, little is known about the financial impact of team-based primary care for secondary prevention of CHD. The purpose of this study was to define the impact of team-based care for CHD on utilization, costs, and revenue of a private primary care practice. STUDY DESIGN: Interrupted time series analysis. METHODS: Between March 1, 2010, and March 31, 2013, we assisted a private medical practice, comprising 5 primary care clinic sites, to organize and deliver team based care for patients with CHD. We used billing records and the registered nurse care manager's diary to calculate the cost of team-based care, differences in the average number of visits per patient, and revenue per patient before and after the implementation of team-based care. RESULTS: The net cost of team-based primary care was $291 per patient over the 1-year period of observation. CONCLUSIONS: The findings from this study are consistent with other economic analyses of team-based care and suggest that payment for care must be restructured if patients are expected to enjoy the benefits of team-based primary care. PMID- 27556831 TI - Opinions on the Hospital Readmission Reduction Program: results of a national survey of hospital leaders. AB - OBJECTIVES: To determine the opinions of US hospital leadership on the Hospital Readmissions Reduction Program (HRRP), a national mandatory penalty-for performance program. STUDY DESIGN: We developed a survey about federal readmission policies. We used a stratified sampling design to oversample hospitals in the highest and lowest quintile of performance on readmissions, and hospitals serving a high proportion of minority patients. METHODS: We surveyed leadership at 1600 US acute care hospitals that were subject to the HRRP, and achieved a 62% response rate. Results were stratified by the size of the HRRP penalty that hospitals received in 2013, and adjusted for nonresponse and sampling strategy. RESULTS: Compared with 36.1% for public reporting of readmission rates and 23.7% for public reporting of discharge processes, 65.8% of respondents reported that the HRRP had a "great impact" on efforts to reduce readmissions. The most common critique of the HRRP penalty was that it did not adequately account for differences in socioeconomic status between hospitals (75.8% "agree" or "agree strongly"); other concerns included that the penalties were "much too large" (67.7%), and hospitals' inability to impact patient adherence (64.1%). These sentiments were each more common in leaders of hospitals with higher HRRP penalties. CONCLUSIONS: The HRRP has had a major impact on hospital leaders' efforts to reduce readmission rates, which has implications for the design of future quality improvement programs. However, leaders are concerned about the size of the penalties, lack of adjustment for socioeconomic and clinical factors, and hospitals' inability to impact patient adherence and postacute care. These concerns may have implications as policy makers consider changes to the HRRP, as well as to other Medicare value-based payment programs that contain similar readmission metrics. PMID- 27556832 TI - Association among change in medical costs, level of comorbidity, and change in adherence behavior. AB - OBJECTIVES: Interventions to improve medication adherence are effective, but resource intensive. Interventions must be targeted to those who will potentially benefit most. We examined what heterogeneity exists in the value of adherence based on levels of comorbidity, and the changes in spending on medical services that followed changes in adherence behavior. STUDY DESIGN: Retrospective cohort study examining medical spending for 2 years (April 1, 2011, to March 31, 2013) in commercial insurance beneficiaries. METHODS: Multivariable linear modeling was used to adjust for differences in patient characteristics. Analyses were performed at the patient/condition level in 2 cohorts: adherent at baseline and nonadherent at baseline. RESULTS: We evaluated 857,041 patients, representing 1,264,797 patient therapies consisting of 40% high cholesterol, 48% hypertension, and 12% diabetes. Among those with 3 or more conditions, annual savings associated with becoming adherent were $5341, $4423, and $2081 for patients with at least diabetes, hypertension, and high cholesterol, respectively. The increased costs for patients in this group who became nonadherent were $4653, $7946, and $4008, respectively. Depending on the condition and the direction of behavior change, savings were 2 to 7 times greater than the value for individuals with fewer than 3 conditions. In most cases, the value of preventing nonadherence (ie, persistence) was greater than the value of moving people who are nonadherent to an adherent state. CONCLUSIONS: There is important heterogeneity in the impact of medication adherence on medical spending. Clinicians and policy makers should consider this when promoting the change of adherence behavior. PMID- 27556833 TI - Choosing Wisely: spine imaging. PMID- 27556834 TI - Burden of illness for super-refractory status epilepticus patients. AB - OBJECTIVE: To provide an estimate of the annual number of super-refractory status epilepticus (SRSE) cases in the US and to evaluate utilization of hospital resources by these patients. METHODS: The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.g. benzodiazepines, anti-epileptic drugs (AEDs), and ventilator use). Secondary analyses were conducted using more restrictive algorithms for SRSE. RESULTS: A total of 6,325 hospital discharges were classified as SRSE cases from a total of 5,300,000 hospital discharges. Applying a weighting based on hospital characteristics and 2012 US demographics, this projected to an estimated 41,156 cases of SRSE in the US during 2012, an estimated incidence rate of ~13/100,000 annually for SRSE in the US. Secondary analyses using stricter SRSE algorithms resulted in estimated incidence rates of ~11/100,000 and 8/100,000 annually. The mean LOS for SRSE hospitalizations was 16.5 days (median =11; interquartile range [IQR] = 6-20), and the mean ICU LOS was 9.3 days (median =6; IQR =3-12). The mean cost of an SRSE hospitalization was $51,247 (median = $33,294; 95% CI = $49,634-$52,861). LIMITATIONS: The analysis uses ICD-9 diagnostic codes and claims information, and there are inherent limitations in any methodology based on treatment protocol, which created challenges in distinguishing with complete accuracy between SRSE, RSE, and SE on the basis of care patterns in the database. CONCLUSION: SRSE is associated with high mortality and morbidity, which place a high burden on healthcare resources. Projections based upon the findings of this study suggest an estimated 25,821-41,959 cases of SRSE may occur in the US each year, but more in-depth studies are required. PMID- 27556835 TI - Comparing the standards of one metabolic equivalent of task in accurately estimating physical activity energy expenditure based on acceleration. AB - The purpose of the study is to analyse how the standard of resting metabolic rate (RMR) affects estimation of the metabolic equivalent of task (MET) using an accelerometer. In order to investigate the effect on estimation according to intensity of activity, comparisons were conducted between the 3.5 ml O2 . kg-1 . min-1 and individually measured resting VO2 as the standard of 1 MET. MET was estimated by linear regression equations that were derived through five-fold cross-validation using 2 types of MET values and accelerations; the accuracy of estimation was analysed through cross-validation, Bland and Altman plot, and one way ANOVA test. There were no significant differences in the RMS error after cross-validation. However, the individual RMR-based estimations had as many as 0.5 METs of mean difference in modified Bland and Altman plots than RMR of 3.5 ml O2 . kg-1 . min-1. Finally, the results of an ANOVA test indicated that the individual RMR-based estimations had less significant differences between the reference and estimated values at each intensity of activity. In conclusion, the RMR standard is a factor that affects accurate estimation of METs by acceleration; therefore, RMR requires individual specification when it is used for estimation of METs using an accelerometer. PMID- 27556836 TI - Health Services Utilization, Specialist Care, and Time to Diagnosis with Inflammatory Bowel Disease in Immigrants to Ontario, Canada: A Population-Based Cohort Study. AB - BACKGROUND: Canada has amongst the highest incidence of inflammatory bowel disease (IBD) in the world, and the highest proportion of immigrants among G8 nations. We determined differences in prediagnosis delay, specialist care, health services use, and risk of surgery in immigrants with IBD. METHODS: All incident cases of IBD in children (1994-2009) and adults (1999-2009) were identified from population-based health administrative data in Ontario, Canada. Linked immigration data identified those who arrived to Ontario after 1985. We compared time to diagnosis, postdiagnosis health services use (IBD specific and related), physician specialist care in immigrants and nonimmigrants, and risk of surgery between immigrants and nonimmigrants. RESULTS: Thousand two hundred two immigrants were compared with 22,990 nonimmigrants. Immigrants had similar time to diagnosis as nonimmigrants for Crohn's (hazard ratio [HR] 1.002; 95% confidence intervals [CIs] 0.89-1.12) and ulcerative colitis (HR 1.073; 95% CI 0.95-1.21). For outpatient visits, immigrants with IBD were seen by gastroenterologists more often than nonimmigrants. Immigrants had greater IBD specific outpatient health services use after diagnosis (odds ratio 1.24; 95% CI 1.15-1.33), emergency department visits (odds ratio 1.57, 95% CI 1.30-1.91), and hospitalizations (odds ratio 1.19; 95% CI 1.02-1.40). In immigrants, there was lower risk of surgery for Crohn's (HR 0.66, 95% CI 0.43-0.99) and ulcerative colitis (HR 0.52, 95% CI 0.31-0.87). CONCLUSIONS: Immigrants to Canada had greater outpatient and specialty care and lower risk of surgery, with no delay in diagnosis, indicating appropriate use of the health system. PMID- 27556837 TI - Vedolizumab in Inflammatory Bowel Disease Associated with Autoimmune Liver Disease Pre- and Postliver Transplantation: A Case Series. PMID- 27556839 TI - SEER*Educate: Use of Abstracting Quality Index Scores to Monitor Improvement of All Employees. AB - Integral parts of the Seattle-Puget Sound's Cancer Surveillance System registry's continuous improvement model include the incorporation of SEER*Educate into its training program for all staff and analyzing assessment results using the Abstracting Quality Index (AQI). The AQI offers a comprehensive measure of overall performance in SEER*Educate, which is a Web-based application used to personalize learning and diagnostically pinpoint each staff member's place on the AQI continuum. The assessment results are tallied from 6 abstracting standards within 2 domains: incidence reporting and coding accuracy. More than 100 data items are aligned to 1 or more of the 6 standards to build an aggregated score that is placed on a continuum for continuous improvement. The AQI score accurately identifies those individuals who have a good understanding of how to apply the 6 abstracting standards to reliably generate high quality abstracts. PMID- 27556838 TI - Culex Species Mosquitoes and Zika Virus. AB - Recent reports of Zika virus (ZIKV) isolates from Culex species mosquitoes have resulted in concern regarding a lack of knowledge on the number of competent vector species for ZIKV transmission in the new world. Although observations in the field have demonstrated that ZIKV isolation can be made from Culex species mosquitoes, the detection of ZIKV in these mosquitoes is not proof of their involvement in a ZIKV transmission cycle. Detection may be due to recent feeding on a viremic vertebrate, and is not indicative of replication in the mosquito. In this study, susceptibility of recently colonized Culex species mosquitoes was investigated. The results showed a high degree of refractoriness among members of Culex pipiens complex to ZIKV even when exposed to high-titer bloodmeals. Our finding suggests that the likelihood of Culex species mosquitoes serving as secondary vectors for ZIKV is very low, therefore vector control strategies for ZIKV should remain focused on Aedes species mosquitoes. Our demonstration that Culex quinquefasciatus from Vero Beach, FL, is refractory to infection with ZIKV is especially important and timely. Based on our data, we would conclude that the autochthonous cases of Zika in Florida are not due to transmission by C. quinquefasciatus, and so control efforts should focus on other species, logically Aedes aegypti and Aedes albopictus. PMID- 27556840 TI - Development of National Program of Cancer Registries SAS Tool for Population Based Cancer Relative Survival Analysis. AB - BACKGROUND: Studying population-based cancer survival by leveraging the high quality cancer incidence data collected by the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) can offer valuable insight into the cancer burden and impact in the United States. We describe the development and validation of a SASmacro tool that calculates population-based cancer site-specific relative survival estimates comparable to those obtained through SEER*Stat. METHODS: The NPCR relative survival analysis SAS tool (NPCR SAS tool) was developed based on the relative survival method and SAS macros developed by Paul Dickman. NPCR cancer incidence data from 25 states submitted in November 2012 were used, specifically cases diagnosed from 2003 to 2010 with follow-up through 2010. Decennial and annual complete life tables published by the National Center for Health Statistics (NCHS) for 2000 through 2009 were used. To assess comparability between the 2 tools, 5-year relative survival rates were calculated for 25 cancer sites by sex, race, and age group using the NPCR SAS tool and the National Cancer Institute's SEER*Stat 8.1.5 software. A module to create data files for SEER*Stat was also developed for the NPCR SAS tool. RESULTS: Comparison of the results produced by both SAS and SEER*Stat showed comparable and reliable relative survival estimates for NPCR data. For a majority of the sites, the net differences between the NPCR SAS tool and SEER*Stat produced relative survival estimates ranged from -0.1% to 0.1%. The estimated standard errors were highly comparable between the 2 tools as well. IMPLICATIONS: The NPCR SAS tool will allow researchers to accurately estimate cancer 5-year relative survival estimates that are comparable to those produced by SEER*Stat for NPCR data. Comparison of output from the NPCR SAS tool and SEER*Stat provided additional quality control capabilities for evaluating data prior to producing NPCR relative survival estimates. PMID- 27556841 TI - Timeliness of Breast Cancer Treatment in Delaware. AB - Studies have shown timely screening, diagnosis, and treatment of breast cancer reduces mortality rates. The objective of this study was to evaluate the overall timeliness of breast cancer diagnosis and treatment for Delawarean women using the Centers for Disease Control and Prevention (CDC)'s National Breast and Cervical Cancer Early Detection Program (NBCCEDP)'s recommendations of 60 days maximum for screening to diagnosis and 60 days maximum for diagnosis to treatment. This study analyzed Delaware Cancer Registry data for female Delawarean breast cancer patients diagnosed in 2010 who had valid screening, diagnosis, and treatment dates. Calculations of 3 time intervals were performed: screening to diagnosis (time interval A), diagnosis to treatment (time interval B), and screening to treatment (time interval C). The mean and median for time intervals A (21.2 days, 17.0 days), B (27.8 days, 25.0 days), and C (49.0 days, 42.0 days) met CDC recommendations. Our results show most Delawarean women who had valid screening, diagnosis, and treatment dates received a diagnosis within 60 days of screening and first course of treatment occurred within 60 days of diagnosis and therefore met the NBCCEDP recommendations. PMID- 27556842 TI - Statistical Process Control: A Quality Tool for a Venous Thromboembolic Disease Registry. AB - OBJECTIVE: We aim to describe Statistical Control Process as a quality tool for the Institutional Registry of Venous Thromboembolic Disease (IRTD), a registry developed in a community-care tertiary hospital in Buenos Aires, Argentina. METHODS: The IRTD is a prospective cohort. The process of data acquisition began with the creation of a computerized alert generated whenever physicians requested imaging or laboratory study to diagnose venous thromboembolism, which defined eligible patients. The process then followed a structured methodology for patient's inclusion, evaluation, and posterior data entry. To control this process, process performance indicators were designed to be measured monthly. These included the number of eligible patients, the number of included patients, median time to patient's evaluation, and percentage of patients lost to evaluation. Control charts were graphed for each indicator. RESULTS: The registry was evaluated in 93 months, where 25,757 patients were reported and 6,798 patients met inclusion criteria. The median time to evaluation was 20 hours (SD, 12) and 7.7% of the total was lost to evaluation. Each indicator presented trends over time, caused by structural changes and improvement cycles, and therefore the central limit suffered inflexions. CONCLUSION: Statistical process control through process performance indicators allowed us to control the performance of the registry over time to detect systematic problems. We postulate that this approach could be reproduced for other clinical registries. PMID- 27556843 TI - The Impact of Preoperative Magnetic Resonance Imaging in Detecting Additional Disease in Breast Cancer Patients. AB - In newly diagnosed breast cancer patients, it has been shown that magnetic resonance imaging (MRI) detects additional cancer not found on mammography and thus is useful to map out the extent of disease in the affected breast.1 Others have shown MRI valuable in detecting occult disease in the contralateral breast.2 More recently, it has been reported that MRI is suitable for guiding surgical decisions, especially in younger women with lobular cancer and/ or increased breast density.3 Consequently, MRI is increasingly being used for clinical staging of breast cancer and is currently supported by the National Comprehensive Cancer Network (NCCN) to define the extent and/or multifocality of cancer in the ipsilateral breast, and to screen the contralateral breast at the time of initial diagnosis.4. PMID- 27556844 TI - Differentiating Chronic Lymphocytic Leukemia from Small Lymphocytic Lymphoma: A Manitoba Cancer Registry Perspective. AB - Monoclonal B-cell lymphocytosis (MBL) does not have a World Health Organization (WHO) International Classification of Diseases for Oncology (ICD-O) morphology code as it is not currently recognized as a reportable disease. Although MBL is premalignant, patients diagnosed with MBL need to be monitored as they eventually progress to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Working together, the Manitoba CLL Disease Site Group (DSG) and the Manitoba Cancer Registry developed a way to record and track these patients to ensure they receive the proper follow-up care. PMID- 27556845 TI - Maximizing the Impact of Cancer Care Conferences. PMID- 27556846 TI - A Plan to Improve Melanoma Tumor Depth Data Quality in the Surveillance, Epidemiology, and End Results Program. AB - In light of the recent assessment done for ProstateSpecific Antigen values in the Surveillance, Epidemiology, and End Results (SEER) Program, it is possible that coding procedures for melanoma tumor depth may have similar quality issues. Potential errors that have been initially identified are implied decimal errors, transcription errors, and incomplete information. Because of the SEER Program's commitment to high data quality standards, various studies are being planned to review and adjudicate incorrect lab values for several different data items in the SEER data collection. PMID- 27556847 TI - CP3R: An Important Tool. AB - The Web-based Cancer Program Practice Profile Reports (CP3R) offer providers comparative information to assess adherence to and consideration of standard-of care therapies for major cancers. The tool helps facilities practice continuous improvement to ensure quality of patient care. The poster will illustrate a process to ensure the presentation of data at a compliance level. PMID- 27556849 TI - The Rapid Quality Reporting System (RQRS): Make it Work for You! PMID- 27556848 TI - SEER*Educate-Learn by Doing. AB - Historically, newly hired staff members were trained using a labor intensive one on-one strategy and experienced staff participated in monthly education meetings. With the ever-expanding data collection requirements and guideline changes, helping every staff member remain current became impossible to achieve using this methodology. To better address the training needs of each staff member and to do so in a cost effective way, a comprehensive e-training platform was designed. PMID- 27556850 TI - Primary Payer at DX: Issues with Collection and Assessment of Data Quality. AB - An individual's access to health insurance influences the amount and type of health services a patient receives for prevention and treatment, and, ultimately, influences survival. The North American Association of Central Cancer Registries (NAACCR) Item #630, Primary Payer at DX, is a required field intended to document health insurance status for the purpose of supporting patterns-of-care studies and other research. However, challenges related to the uniformity of collection and availability of data needed to populate this field diminish the value of the Primary Payer at DX data. A NAACCR taskforce worked on issues surrounding the collection of Primary Payer at DX; including proposing a crosswalk between Primary Payer at DX and the new Public Health Payment Typology standard, often available in hospital discharge databases. However, there are issues with compatibility between coding systems, intent of data collection, timelines for coding insurance, and changes in insurance coverage (partly due to the Affordable Care Act) that continue to complicate the collection and use of Primary Payer at DX data. PMID- 27556851 TI - Where Do I Find Those Site-Specific Factors? PMID- 27556852 TI - Identifying Class of Case to Improve Data Quality. AB - Accurately identifying Class of Case (Figure 1) is crucial in understanding the type of data that can be analyzed in determining valuable patient population characteristics for your cancer program targeted community. Class of Case has a large impact on statistical analysis and public reporting. Physician/institution mergers and acquisitions, contracts, and other agreements make determining class of case challenging. PMID- 27556853 TI - Onboarding the New Cancer Registrar. AB - In the search for new registrars, we often find that applicants have no medical experience or knowledge of the cancer registry. This poster will illustrate an onboarding process on how to train and foster the professional development of a new cancer registrar (Figure 1). PMID- 27556854 TI - Rapid Site-Specific Case Ascertainment. PMID- 27556855 TI - Bridging the Gap. AB - The view from the top of Hoover Dam looking south over the Colorado River was breathtaking! My friend and I stood there in silence, taking it all in. I had visited Hoover Dam on many occasions, but this visit was the first time I had seen the arch bridge that carries US Route 93 over the river and joins Nevada and Arizona states. It was a beautiful day, the temperature was perfect, and there was a slight breeze coming from Lake Mead behind us as we took in the view. PMID- 27556856 TI - MYO9B gene polymorphisms are associated with the risk of inflammatory bowel diseases. AB - Myosin IXB (MYO9B) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between MY09B gene polymorphisms and the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and CNKI databases were identified. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Ten studies published in eight papers reporting 8,975 cases and 9,482 controls were included in this meta-analysis. Five MY09B gene polymorphisms were evaluated: rs1545620, rs962917, rs1457092, rs2305764, and rs2305767. Our data suggested that the rs1545620 polymorphism was associated with a decreased risk of IBD. A similar result was found for rs2305767 and UC. The rs962917 single nucleotide polymorphism (SNP) increased the risk of IBD, CD and UC. Moreover, rs1457092 increased the risk of IBD and UC. Rs2305764 was also associated with an increased risk of IBD. Furthermore, stratification analyses indicated that rs1545620 decreased the risk of IBD, while rs962917 increased the risk of IBD, CD and UC in Caucasian populations. To sum up, our data indicate that these five SNPs in MY09B are significantly associated with the risk of IBD. PMID- 27556857 TI - Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer. AB - Tumour cell-extracellular matrix (ECM) interactions are fundamental for discrete steps in breast cancer progression. In particular, cancer cell adhesion to ECM proteins present in the microenvironment is critical for accelerating tumour growth and facilitating metastatic spread. To assess the utility of tumour cell ECM adhesion as a means for discovering prognostic factors in breast cancer survival, here we perform a systematic phenotypic screen and characterise the adhesion properties of a panel of human HER2 amplified breast cancer cell lines across six ECM proteins commonly deregulated in breast cancer. We determine a gene expression signature that defines a subset of cell lines displaying impaired adhesion to laminin. Cells with impaired laminin adhesion showed an enrichment in genes associated with cell motility and molecular pathways linked to cytokine signalling and inflammation. Evaluation of this gene set in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort of 1,964 patients identifies the F12 and STC2 genes as independent prognostic factors for overall survival in breast cancer. Our study demonstrates the potential of in vitro cell adhesion screens as a novel approach for identifying prognostic factors for disease outcome. PMID- 27556858 TI - Dendritic cell-derived nitric oxide inhibits the differentiation of effector dendritic cells. AB - Dendritic cells (DCs) play a pivotal role in the development of effective immune defense while avoiding detrimental inflammation and autoimmunity by regulating the balance of adaptive immunity and immune tolerance. However, the mechanisms that govern the effector and regulatory functions of DCs are incompletely understood. Here, we show that DC-derived nitric oxide (NO) controls the balance of effector and regulatory DC differentiation. Mice deficient in the NO-producing enzyme inducible nitric oxide synthase (iNOS) harbored increased effector DCs that produced interleukin-12, tumor necrosis factor (TNF) and IL-6 but normal numbers of regulatory DCs that expressed IL-10 and programmed cell death-1 (PD 1). Furthermore, an iNOS-specific inhibitor selectively enhanced effector DC differentiation, mimicking the effect of iNOS deficiency in mice. Conversely, an NO donor significantly suppressed effector DC development. Furthermore, iNOS-/- DCs supported enhanced T cell activation and proliferation. Finally iNOS-/- mice infected with the enteric pathogen Citrobacter rodentium suffered more severe intestinal inflammation with concomitant expansion of effector DCs in colon and spleen. Collectively, our results demonstrate that DC-derived iNOS restrains effector DC development, and offer the basis of therapeutic targeting of iNOS in DCs to treat autoimmune and inflammatory diseases. PMID- 27556859 TI - A novel molecular and clinical staging model to predict survival for patients with esophageal squamous cell carcinoma. AB - Current prognostic factors fail to accurately determine prognosis for patients with esophageal squamous cell carcinoma (ESCC) after surgery. Here, we constructed a survival prediction model for prognostication in patients with ESCC. Candidate molecular biomarkers were extracted from the Gene Expression Omnibus (GEO), and Cox regression analysis was performed to determine significant prognostic factors. The survival prediction model was constructed based on cluster and discriminant analyses in a training cohort (N=205), and validated in a test cohort (N=207). The survival prediction model consisting of two genes (UBE2C and MGP) and two clinicopathological factors (tumor stage and grade) was developed. This model could be used to accurately categorize patients into three groups in the test cohort. Both disease-free survival and overall survival differed among the diverse groups (P<0.05). In summary, we have developed and validated a predictive model that is based on two gene markers in conjunction with two clinicopathological variables, and which can accurately predict outcomes for ESCC patients after surgery. PMID- 27556860 TI - Novel synthetic cyclic integrin alphavbeta3 binding peptide ALOS4: Antitumor activity in mouse melanoma models. AB - ALOS4, a unique synthetic cyclic peptide without resemblance to known integrin ligand sequences, was discovered through repeated biopanning with pIII phage expressing a disulfide-constrained nonapeptide library. Binding assays using a FITC-labeled analogue demonstrated selective binding to immobilized alphavbeta3 and a lack of significant binding to other common proteins, such as bovine serum albumin and collagen. In B16F10 cell cultures, ALOS4 treatment at 72 h inhibited cell migration (30%) and adhesion (up to 67%). Immunofluorescent imaging an ALOS4 FITC analogue with B16F10 cells demonstrated rapid cell surface binding, and uptake and localization in the cytoplasm. Daily injections of ALOS4 (0.1, 0.3 or 0.5 mg/kg i.p.) to mice inoculated with B16F10 mouse melanoma cells in two different cancer models, metastatic and subcutaneous tumor, resulted in reduction of lung tumor count (metastatic) and tumor mass (subcutaneous) and increased survival of animals monitored to 45 and 60 days, respectively. Examination of cellular activity indicated that ALOS4 produces inhibition of cell migration and adhesion in a concentration-dependent manner. Collectively, these results suggest that ALOS4 is a structurally-unique selective alphavbeta3 integrin ligand with potential anti-metastatic activity. PMID- 27556862 TI - Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems. AB - Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant reduction in tumor volume in TMZ/zinc treated mice relative to treatment with TMZ alone. Our results suggest that zinc may serve as a potentiator of TMZ therapy in GBM patients. PMID- 27556864 TI - Erythrocyte adenosine deaminase levels are elevated in Diamond Blackfan anemia but not in the 5q- syndrome. PMID- 27556861 TI - Inhibition of interleukin-1beta-induced endothelial tissue factor expression by the synthetic cannabinoid WIN 55,212-2. AB - The role of cannabinoids in thrombosis remains controversial. In view of the primary importance of tissue factor (TF) in blood coagulation and its involvement in the pathology of several cardiovascular, inflammatory and neoplastic diseases, a regulation of this initial procoagulant signal seems to be of particular interest. Using human umbilical vein endothelial cells (HUVEC) the present study investigated the impact of the synthetic cannabinoid WIN 55,212-2 on interleukin (IL)-1beta-induced TF expression and activity. WIN 55,212-2 caused a time- and concentration-dependent suppression of IL-1beta-induced TF protein accompanied by decreases in TF mRNA and activity. Inhibition of TF protein expression by WIN 55,212-2 was mimicked by its cannabinoid receptor-inactive enantiomer WIN 55,212 3 but not by structurally unrelated phyto-, endo- and synthetic cannabinoids. In addition, the inhibitory effect of WIN 55,212-2 was not reversed by antagonists to cannabinoid receptors (CB1, CB2) or transient receptor potential vanilloid 1. Mechanistic approaches revealed WIN 55,212-2 to suppress IL-1beta-induced TF expression via inhibition of ceramide formation and via decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinases. Further inhibitor experiments demonstrated neutral sphingomyelinase (nSMase) to confer ceramide generation upon IL-1beta treatment with the parallel IL-1beta mediated activation of MAPKs occurring via an nSMase-independent pathway. Finally, a receptor-independent inhibition of IL-1beta-induced TF protein by WIN 55,212-2 was confirmed in human blood monocytes. Collectively, this data provide a hitherto unknown receptor-independent anticoagulatory action of the cannabinoid WIN 55,212-2. PMID- 27556865 TI - Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora. AB - Seven new 14-membered macrolides, pestalotioprolides C (2), D-H (4-8), and 7-O methylnigrosporolide (3), together with four known analogues, pestalotioprolide B (1), seiricuprolide (9), nigrosporolide (10), and 4,7-dihydroxy-13-tetradeca 2,5,8-trienolide (11), were isolated from the mangrove-derived endophytic fungus Pestalotiopsis microspora. Their structures were elucidated by analysis of NMR and MS data and by comparison with literature data. Single-crystal X-ray diffraction analysis was used to confirm the absolute configurations of 1, 2, and 10, while Mosher's method and the TDDFT-ECD approach were applied to determine the absolute configurations of 5 and 6. Compounds 3-6 showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC50 values of 0.7, 5.6, 3.4, and 3.9 MUM, respectively, while compound 5 showed potent activity against the human ovarian cancer cell line A2780 with an IC50 value of 1.2 MUM. Structure-activity relationships are discussed. Coculture of P. microspora with Streptomyces lividans caused a roughly 10-fold enhanced accumulation of compounds 5 and 6 compared to axenic fungal control. PMID- 27556867 TI - Definitions of Risky and Problematic Cannabis Use: A Systematic Review. AB - Although cannabis is widely used, it remains unclear which consumption patterns are more likely to produce future consequences (risky/hazardous use) or current damage (problematic/harmful use). This unresolved issue contributes to cannabis public health implications. In order to facilitate further consensus, this review analyzes previously used definitions in the literature. METHODS: This systematic review was performed following the PRISMA guidelines. Articles published before October 2015 in the Medline, Scopus-Elsevier, ISI-Web of Knowledge and Cochrane databases and fulfilling a-priori decided criteria were retrieved. Definitions in preselected websites of national and international organizations addressing drug problems were also included. RESULTS: Definitions identified in articles (n = 46) and official websites (n = 3) widely varied from each other. Weekly cannabis use was mostly considered risky. Problematic cannabis use was mostly described with the Cannabis Abuse and Screening Test. Evidence-based definitions as well as information on quantities consumed, time-frames and special considerations for risky groups were very limited. CONCLUSIONS: Working on official definitions is highly necessary as criteria used remain incomplete, leading to increased confusion in the field. Recommendations to improve existing definitions are given. PMID- 27556866 TI - Marijuana Use Among Young Black Men Who Have Sex With Men and the HIV Care Continuum: Findings From the uConnect Cohort. AB - BACKGROUND: Young Black men who have sex with men (YBMSM) are at highest risk for HIV seroconversion in the United States. Successful movement through the HIV care continuum is an important intervention for limiting onwards HIV transmission. OBJECTIVE: Little data exists on how substances most commonly used by YBMSM, such as marijuana, are related to the HIV continuum, which represents the primary aim of this study. METHODS: A cohort of YBMSM (n = 618) was generated through respondent-driven sampling. Frequency of marijuana use and marijuana use as a sex drug were assessed across the HIV care continuum using weighted logistic regression models. RESULTS: Study participants reported more intermittent marijuana use (n = 254, 56.2%) compared to heavy use (n = 198, 43.8%). Our sample contained 212 (34.3%) HIV seropositive participants of which 52 (24.5%) were unaware of their HIV positive status. Study participants who were heavy marijuana users were more likely to be unaware of their HIV seropositive status (AOR: 4.18; 95% CI 1.26, 13.89). All other stages in the care continuum demonstrated no significant differences between those who use marijuana intermittently or heavily or as a sex-drug and nonusers. CONCLUSIONS: YBMSM who used marijuana heavily were more likely to be HIV-positive unaware than those who never used marijuana. Findings were inconclusive regarding the relationships between marijuana use and other HIV care continuum metrics. However, knowledge of ones' HIV status is a critical requirement for engaging in care and may have implications for onwards HIV transmission. PMID- 27556868 TI - Public Perspectives on Expanding Naloxone Access to Reverse Opioid Overdoses. AB - BACKGROUND: Opioid overdoses can often be reversed with naloxone hydrochloride. Past studies on attitudes toward expanded naloxone access have surveyed drug users, family members, and providers. OBJECTIVES: To explore how the general public perceives take-home or nonmedical first-responder access to naloxone to reverse opioid overdoses. Additionally, little is known about how support for expanded access is related to participant's endorsement of Individualism and Just World Belief-colloquially people getting what they deserve and deserving what they get. METHODS: Lay participants completed an online survey examining concerns with and support for expanding naloxone access. Just World Belief, Individualism, and participants' dependence history were also measured. Four different hypothetical situations were considered, varying according to type of opioid (heroin versus nonmedical prescription opioid) and recipient (suburban middle class versus recent parolee). RESULTS: Most participants agreed with at least some degree of expanded access. Analyses of variance indicated that type of opioid or recipient did not affect attitudes toward expansion. Pearson correlations and multiple regressions revealed that endorsement of Just World Beliefs and Individualism were associated with greater concerns with and less support for expansion. IMPORTANCE: While there is general agreement with some degree of expanding naloxone access, participants' level of endorsement was influenced by their level of individualism and belief in a just world. These factors need to be considered in how to best frame messages to maximize layperson support for expansion. PMID- 27556869 TI - Estimates of the Absolute and Relative Strengths of Diverse Alcoholic Drinks by Young People. AB - BACKGROUND: Evidence suggests that college students are often unclear about how much alcohol is present in different drinks. OBJECTIVES: To evaluate the abilities of students to estimate the alcohol contents of drinks, both in relative and absolute terms, and to examine how alcohol strength informs behavior. METHODS: For 10 popular drinks that varied by alcohol content, beverage and volume, 209 UK university students rank-ordered the drinks according to total alcohol content and then estimated, for each drink, the number of UK "units" of alcohol contained and its percentage alcohol-by-volume (% ABV). Participants also reported the importance of drink strength as a factor in drink choice, and its influence in different scenarios. RESULTS: There was low but significant concordance between participants' rank-orderings of drinks by strength, and the correlation of mean ranks with correct ranks was also significant. However, their explicit estimates of the numbers of "units" in the drinks, and their % ABV values, often diverged dramatically from actual values. Participants tended to overestimate the unit contents of spirit-based drinks but underestimated the unit contents of beers and wine; women were consistently less accurate than men, typically making greater underestimates for commonly-consumed drinks. Over one third of the sample reported that strength influenced drink choice, but its importance ranked below flavor and cost; drink strength might contribute to drink choice depending on the drinking situation. Conclusion/Importance: Young drinkers (women especially) have a poor awareness of the alcohol contents of different drinks, particularly wines and beers, but they make better judgments of relative strength. PMID- 27556870 TI - Substance Misuse and Behavioral Adjustment Problems in Irish Adolescents: Examining Contextual Risk and Social Proximal Factors. AB - BACKGROUND: Using an ecological perspective to examine the roles of contextual factors and proximal social processes, the current study examined problem behavior among adolescents. OBJECTIVE: The study examined how family, peer, and school processes mediate the relationship between cumulative contextual risk and problem behavior, and whether these mediating relationships are moderated by gender. METHOD: Data were obtained from the My World Survey Second Level, a cross sectional national survey assessing risk and protective factors of mental health among 6062 adolescents aged 12-19 years (M = 14.93, SD = 1.62). Using risk factors from socioeconomic, community, and family levels, a cumulative contextual risk index (CCRI) was created to identify adolescents at increased risk of problem behavior in Ireland. Conditional process analysis examined whether gender moderated the relationship between the CCRI and problem behaviors (alcohol behavior, poorer behavioral adjustment, and problematic substance use) as mediated by five proximal social variables, family cohesion, mother criticism, father criticism, peer connectedness, and school connectedness. RESULTS: Using Hayes' (2013) SPSS macro for conditional process analyses, with age as a covariate, gender was shown to moderate the mediated relationships between CCRI and problem behaviors, via mother criticism and peer connectedness. Of note, a positive association was observed between high peer connectedness and alcohol risk behavior, highlighting the need to examine additional aspects of peer context including group norms and peer pressure. CONCLUSION: The study provides valuable and practical implications for informing research, interventions, and social policy at family, peer, and school levels. PMID- 27556871 TI - Anger Expression Style Predicts the Domain of the First Smoking Relapse After a Quit Attempt. AB - BACKGROUND: Risk for smoking relapse may be associated with context-dependent social and behavioral cues. However, lack of research examining the role of trait negative mood such as anger in this relationship and assessment of objective indices related to smoking status (e.g., biochemical measures) may limit existing findings. We examined the roles of trait anger, habitual anger expression behavior, and the situation in which the first incident of smoking lapse following a quit attempt occurs. METHODS: One-hundred and five smokers interested in cessation (mean age, SD: 34.7 +/- 11.8) set a quit day and attended multiple post-quit assessments where they were asked to provide biochemical measures including exhaled carbon monoxide (CO) and self-report measurements, including smoking status. RESULTS: Eighty-eight participants (40 women) returned to smoking over the 12-month study period. Self-reported smoking status was verified by exhaled CO measurements. Thirty-one percent of participants who relapsed reported the first lapse occurring at home, 15% at work, 14% at a restaurant or a bar, and 8% in a car. Multinomial logistic regression models found that high levels of anger-out were associated with smoking relapse in situations other than work or home (p <.05). CONCLUSIONS: These results expand prior work suggesting habitual anger expression style may moderate associations between situational factors and risk for smoking relapse, highlighting the need to incorporate findings in treatment methods. Absence of gender differences suggests the situational factors explored here affect relapse independent of gender. PMID- 27556872 TI - The Relationship Between Hope and Adolescent Likelihood to Endorse Substance Use Behaviors in a Sample of Marginalized Youth. AB - BACKGROUND: Hopefulness has been associated with increased treatment retention and reduced substance abuse among adults, and may be a promising modifiable factor to leverage in substance abuse treatment settings. Few studies have assessed the relationship between hopefulness and substance use in adolescents, particularly those with high-risk backgrounds. OBJECTIVE: We explored whether high hope is associated with less likelihood for engaging in a variety of substance use behaviors in a sample of marginalized adolescents. METHODS: Using logistic regression, we assessed results from a cross-sectional anonymous youth behavior survey (n = 256 youth, ages 14 to 19). We recruited from local youth serving agencies (e.g., homeless shelters, group homes, short-term detention). RESULTS: The sample was almost 60% male and two thirds African American. Unadjusted models showed youth with higher hope had a 50-58% (p = <.05) decreased odds of endorsing heavy episodic drinking, daily tobacco use, recent or lifetime marijuana use, and sex after using substances. Adjusted models showed a 52% decreased odds of lifetime marijuana use with higher hope, and a trend towards less sex after substance use (AOR 0.481; p = 0.065). No other substance use behaviors remained significantly associated with higher hope scores in adjusted models. CONCLUSIONS/IMPORTANCE: Hopefulness may contribute to decreased likelihood of substance use in adolescents. Focusing on hope may be one modifiable target in a comprehensive primary or secondary substance use prevention program. PMID- 27556873 TI - Endoscopic ultrasonography-guided intrapyloric injection of botulinum toxin to treat diabetic gastroparesis. PMID- 27556874 TI - Solid waste management in primary healthcare centers: application of a facilitation tool. AB - OBJECTIVES: to propose a tool to facilitate diagnosis, formulation and evaluation of the Waste Management Plan in Primary Healthcare Centers and to present the results of the application in four selected units. METHOD: descriptive research, covering the stages of formulation /application of the proposed instrument and the evaluation of waste management performance at the units. RESULTS: the tool consists in five forms; specific indicators of waste generation for outpatients healthcare units were proposed, and performance indicators that give scores for compliance with current legislation. In the studied units it is generated common waste (52-60%), infectious-sharps (31-42%) and recyclable (5-17%). The average rates of generation are: 0,09kg of total waste/outpatient assistance and 0,09kg of infectious-sharps waste/outpatient procedure. The compliance with regulations, initially 26-30%, then reached 30-38% a year later. CONCLUSION: the tool showed to be easy to use, bypassing the existence of a complex range of existing regulatory requirements, allowed to identify non-conformities, pointed out corrective measures and evaluated the performance of waste management. In this sense, it contributes to decision making and management practices relating to waste, tasks usually assigned to nurses. It is recommended that the tool be applied in similar healthcare units for comparative studies, and implementation of necessary adaptations for other medical services. PMID- 27556875 TI - Pain from the life cycle perspective: Evaluation and Measurement through psychophysical methods of category estimation and magnitude estimation. AB - OBJECTIVE: to describe acute and chronic pain from the perspective of the life cycle. METHODS: participants: 861 people in pain. The Multidimensional Pain Evaluation Scale (MPES) was used. RESULTS: in the category estimation method the highest descriptors of chronic pain for children/ adolescents were "Annoying" and for adults "Uncomfortable". The highest descriptors of acute pain for children/adolescents was "Complicated"; and for adults was "Unbearable". In magnitude estimation method, the highest descriptors of chronic pain was "Desperate" and for descriptors of acute pain was "Terrible". CONCLUSIONS: the MPES is a reliable scale it can be applied during different stages of development. OBJETIVO: descrever a dor aguda e a cronica na perspectiva do ciclo vital. Metodos: participaram 861 pessoas com dor. Foi utilizada a Escala Multidimensional de Avaliacao da Dor (EMADOR). Resultados: no metodo da estimacao de categoria o descritor da dor cronica de maior atribuicao para criancas e adolescentes foi "Chata" e para adultos foi "Desconfortavel". Os descritores de maior atribuicao para dor aguda em criancas e adolescentes foram "Complicada" e em adultos "Insuportavel". No metodo de estimacao de magnitude, o descritor de maior atribuicao na dor cronica foi "Atormentadora" e na dor aguda foi "Terrivel". CONCLUSOES: a EMADOR e uma escala confiavel e pode ser utilizada nas diferentes etapas do desenvolvimento humano. OBJETIVO: la descripcion del dolor agudo y cronico desde las perspectiva del ciclo de vida. METODOS: participaron 861 personas con dolor. Se utilizo la Escala Multidimensional de Evaluacion del Dolor (EMEDOR). RESULTADOS: en el metodo de estimacion de categoria el descriptor de dolor cronico mas alto para ninos y adolescentes fue de Molesto y para adultos fue Incomodo. Los descriptores mayores de dolor agudo para ninos y adolescentes fueron Complejo y para adultos Insoportable. En el metodo de estimacion de magnitud, el mayor descriptor de dolor cronico fueron Atormentador y el mayor de dolor agudo fue Terrible. CONCLUSIONES: la EMEDOR es una escala confiable y puede ser utilizada en diferentes etapas de desarrollo. PMID- 27556877 TI - Support for learning in the perspective of patient safety in primary health care. AB - OBJECTIVE: to analyze the support for learning, in the perspective of patient safety, offered in the work environment, according to health professionals working in primary care. METHOD: a transversal study, held with 86 health professionals working in primary care. A validated instrument was used, applied via the Internet. Descriptive statistical analysis was undertaken with a presentation of median, mean, standard deviation and coefficient of variation. RESULTS: points which are favorable to supporting learning were evidenced, such as mutual respect, autonomy for organizing the work and valorization of new ideas, which obtained means above 7.0. The variables which hinder the process of learning in the work environment, perceived by the professionals, were: resistance to changes, and excess of work impeding reflection on how to improve the work, with means above 6.0. CONCLUSION: the study found evidence of indicators related to the process of staff development in the area of health and indicates the influence of support for learning for the improvement of the work processes and of patient safety. It is necessary that a culture involving the systematic assessment of educational interventions in health should be established, the aim being to diagnose actions which are more incisive for changing health professionals' attitude and, therefore, clinical practice. PMID- 27556876 TI - Good practices in collecting umbilical cord and placental blood. AB - OBJECTIVE: to identify the factors related to the quality of umbilical cord and placental blood specimens, and define best practices for their collection in a government bank of umbilical cord and placental blood. METHOD: this was a descriptive study, quantitative approach, performed at a government umbilical cord and placental blood bank, in two steps: 1) verification of the obstetric, neonatal and operational factors, using a specific tool for gathering data as non participant observers; 2) definition of best practices by grouping non conformities observed before, during and after blood collection. The data was analyzed using descriptive statistics and the following statistical software: Statistica(r) and R(r). RESULTS: while there was a correlation with obstetrical and neonatal factors, there was a larger correlation with operational factors, resulting in the need to adjust the professional practices of the nursing staff and obstetrical team involved in collecting this type of blood. Based on these non-conformities we defined best practices for nurses before, during and after blood collection. CONCLUSION: the best practices defined in this study are an important management tool for the work of nurses in obtaining blood specimens of high cell quality. PMID- 27556878 TI - Domestic violence on children: development and validation of an instrument to evaluate knowledge of health professionals. AB - OBJECTIVE: to develop and validate an instrument to evaluate the knowledge of health professionals about domestic violence on children. METHOD: this was a study conducted with 194 physicians, nurses and dentists. A literature review was performed for preparation of the items and identification of the dimensions. Apparent and content validation was performed using analysis of three experts and 27 professors of the pediatric health discipline. For construct validation, Cronbach's alpha was used, and the Kappa test was applied to verify reproducibility. The criterion validation was conducted using the Student's t test. RESULTS: the final instrument included 56 items; the Cronbach alpha was 0.734, the Kappa test showed a correlation greater than 0.6 for most items, and the Student t-test showed a statistically significant value to the level of 5% for the two selected variables: years of education and using the Family Health Strategy. CONCLUSION: the instrument is valid and can be used as a promising tool to develop or direct actions in public health and evaluate knowledge about domestic violence on children. PMID- 27556879 TI - Evaluation of the educational technology "Caring for dependent people" by family caregivers in changes and transfers of patients and tube feeding. AB - OBJECTIVE: to assess the contributions of interactive educational technology "Caring for Dependent People" in the development of knowledge to family caregivers of dependent people in a household context and their satisfaction in its use. METHOD: quasi-experimental study, not randomized, of the before and after type, with a convenience sample of 65 family caregivers, from two Medicine services of a hospital in Porto, Portugal. The Control Group consisted of 33 family caregivers and the Experimental Group of 32, identified by consecutive sampling. The experimental group had access to educational technology at home. Data were collected by socio-demographic, satisfaction and evaluation of knowledge questionnaire, about how to feed by nasogastric tube, positioning and transferring the dependent person. The assessment in both groups had two moments: initial, during hospitalization and one month after discharge. RESULTS: the experimental group had a larger increase in knowledge related to the use of the educational technology. In the control group the knowledge did not differ in the two evaluation time points. CONCLUSION: these results confirm the improvement of interactive educational technologies and in the training of family caregivers to care for dependents. This technology successfully met the technical quality and learning needs of caregivers, and was considered easy and stimulating. PMID- 27556880 TI - Prevention of sexually transmitted diseases among visually impaired people: educational text validation. AB - OBJECTIVE: to validate an educational text in the context of Sexually Transmitted Diseases (STD) for visually impaired persons, making it accessible to this population. METHOD: a validation study, in a virtual environment. Data collection occurred from May to September 2012 by emailing the subjects, and was composed by seven content experts about STDs. Analysis was based on the considerations of the experts about Objectives, Structure and Presentation, and Relevance. RESULTS: on the Objectives and Structure and Presentation blocks, 77 (84.6%) and 48 (85.7%) were fully adequate or appropriate, respectively. In the Relevance block, items 3.2 - Allows transfer and generalization of learning, and 3.5 - Portrays aspects needed to clarify the family, showed bad agreement indices of 0.42 and 0.57, respectively. The analysis was followed by reformulating the text according to the relevant suggestions. CONCLUSION: the text was validated regarding the content of sexually transmitted diseases. A total of 35 stanzas were removed and nine others included, following the recommendations of the experts. PMID- 27556881 TI - Glycation and cardiovascular disease in diabetes: A perspective on the concept of metabolic memory. AB - Epidemiological studies have suggested that cumulative diabetic exposure, namely prolonged exposure to chronic hyperglycemia, contributes to the increased risk of cardiovascular disease (CVD) in diabetes. The formation and accumulation of advanced glycation end-products (AGEs) have been known to progress under hyperglycemic conditions. Because AGEs-modified collagens are hardly degraded and remain in diabetic vessels, kidneys and the heart for a long time, even after glycemic control has been achieved, AGEs could become a marker reflecting cumulative diabetic exposure. Furthermore, there is a growing body of evidence that an interaction between AGEs and the receptor for AGEs (RAGE) plays a role in the pathogenesis of CVD. In addition, AGEs induce the expression of RAGE, thus leading to sustained activation of the AGEs-RAGE axis in diabetes. Herein we review the pathological role of the AGEs-RAGE axis in CVD, focusing particularly on the phenomenon of metabolic memory, and discuss the potential clinical usefulness of measuring circulating and tissue levels of AGEs accumulation to evaluate diabetic macrovascular complications. PMID- 27556882 TI - Catalyst-Guided C=Het Hydroarylations by Manganese-Catalyzed Additive-Free C-H Activation. AB - Expedient hydroarylations of C=Het bonds (Het=heteroatom) were accomplished by user-friendly organometallic C-H activation in a positional-selective manner. The broadly applicable C-H functionalization platform enabled the step-economical transformation of aldehydes, ketones, and imines under additive-free reaction conditions. In contrast to palladium, rhodium, ruthenium, rhenium, iridium, nickel, and cobalt catalysis, solely manganese(I) complexes outcompeted the innate substrate control, clearly highlighting the unique power of manganese(I) C H activation catalysis. PMID- 27556884 TI - Bottled SAFT: A Web App Providing SAFT-gamma Mie Force Field Parameters for Thousands of Molecular Fluids. AB - Coarse-grained molecular simulation has become a popular tool for modeling simple and complex fluids alike. The defining aspects of a coarse grained model are the force field parameters, which must be determined for each particular fluid. Because the number of molecular fluids of interest in nature and in engineering processes is immense, constructing force field parameter tables by individually fitting to experimental data is a futile task. A step toward solving this challenge was taken recently by Mejia et al., who proposed a correlation that provides SAFT-gamma Mie force field parameters for a fluid provided one knows the critical temperature, the acentric factor and a liquid density, all relatively accessible properties. Building on this, we have applied the correlation to more than 6000 fluids, and constructed a web application, called "Bottled SAFT", which makes this data set easily searchable by CAS number, name or chemical formula. Alternatively, the application allows the user to calculate parameters for components not present in the database. Once the intermolecular potential has been found through Bottled SAFT, code snippets are provided for simulating the desired substance using the "raaSAFT" framework, which leverages established molecular dynamics codes to run the simulations. The code underlying the web application is written in Python using the Flask microframework; this allows us to provide a modern high-performance web app while also making use of the scientific libraries available in Python. Bottled SAFT aims at taking the complexity out of obtaining force field parameters for a wide range of molecular fluids, and facilitates setting up and running coarse-grained molecular simulations. The web application is freely available at http://www.bottledsaft.org . The underlying source code is available on Bitbucket under a permissive license. PMID- 27556883 TI - An Inhaled Inhibitor of Myristoylated Alanine-Rich C Kinase Substrate Reverses LPS-Induced Acute Lung Injury in Mice. AB - Intratracheal instillation of bacterial LPS is a well-established model of acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Because the myristoylated alanine-rich C kinase substrate (MARCKS) protein is involved in neutrophil migration and proinflammatory cytokine production, we examined whether an aerosolized peptide that inhibits MARCKS function could attenuate LPS-induced lung injury in mice. The peptide, BIO-11006, was delivered at 50 MUM via inhalation either just before intratracheal instillation of 5 MUg of LPS into Balb/C mice, or 4, 12, 24, or 36 hours after LPS instillation. Effects of BIO 11006 were evaluated via analysis of mouse disease-related behavior, lung histology, bronchoalveolar lavage fluid total protein, neutrophil counts and percentages, cytokine (KC [CXCl1, mouse IL-8 equivalent] and TNF-alpha) expression, and activation of NF-kappaB in lung tissue. Treatment with aerosolized BIO-11006 at 0, 4, 12, 24, and even 36 hours after LPS instillation reversed the disease process: mouse behavior returned to normal after two treatments 12 hours apart with the inhaled peptide after LPS injury, whereas control LPS-instilled animals treated with PBS only remained moribund. Histological appearance of inflammation, bronchoalveolar lavage fluid protein levels, leukocyte and neutrophil numbers, KC and TNF-alpha gene and protein expression, and NF-kappaB activation were all significantly attenuated by inhaled BIO-11006 at all time points. These results implicate MARCKS protein in the pathogenesis of ALI/ARDS and suggest that MARCKS-inhibitory peptide(s), delivered by inhalation, could represent a new and potent therapeutic treatment for ALI/ARDS, even if administered well after the disease process has begun. PMID- 27556885 TI - Plasma miR-142 accounting for the missing heritability of CYP3A4/5 functionality is associated with pharmacokinetics of clopidogrel. AB - AIM: To investigate whether plasma miRNAs targeting CYP3A4/5 have an impact on the variance of pharmacokinetics of clopidogrel. MATERIALS & METHODS: The contribution of 13 miRNAs to the CYP3A4/5 gene expression and activity was investigated in 55 liver tissues. The association between plasma miRNAs targeting CYP3A4/5 mRNA and clopidogrel pharmacokinetics was analyzed in 31 patients with coronary heart disease who received 300 mg loading dose of clopidogrel. RESULTS: Among 13 miRNAs, miR-142 was accounting for 12.2% (p = 0.002) CYP3A4 mRNA variance and 9.4% (p = 0.005) CYP3A5 mRNA variance, respectively. Plasma miR-142 was negatively associated with H4 Cmax (r = -0.5269; p = 0.0040) and associated with H4 AUC0-4h (r = -0.4986; p = 0.0069) after 300 mg loading dose of clopidogrel in coronary heart disease patients. CONCLUSION: miR-142 could account for a part of missing heritability of CYP3A4/5 functionality related to clopidogrel activation. PMID- 27556886 TI - Semiparametric time-to-event modeling in the presence of a latent progression event. AB - In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one. We derive the partial likelihood estimators for this problem assuming the latent event is observed, and propose a profile likelihood-based method for estimation when the latent event is unobserved. The baseline hazard in this case is estimated nonparametrically using the EM algorithm, which allows for closed-form Breslow-type estimators at each iteration, bringing improved computational efficiency and stability compared with maximizing the marginal likelihood directly. We present simulation studies to illustrate the finite-sample properties of the method; its use in practice is demonstrated in the analysis of a prostate cancer data set. PMID- 27556887 TI - Molecular Seesaw: How Increased Hydrogen Bonding Can Hinder Excited-State Proton Transfer. AB - A previously unexplained effect in the relative rate of excited-state intramolecular proton transfer (ESIPT) in related indole derivatives is investigated using both theory and experiment. Ultrafast spectroscopy [ J. Phys. Chem. A, 2015, 119, 5618-5625 ] found that although the diol 1,3-bis(2 pyridylimino)-4,7-dihydroxyisoindole exhibits two equivalent intramolecular hydrogen bonds, the ESIPT rate associated with tautomerization of either hydrogen bond is a factor of 2 slower than that of the single intramolecular hydrogen bond in the ethoxy-ol 1,3-bis(2-pyridylimino)-4-ethoxy-7-hydroxyisoindole. Excited state electronic structure calculations suggest a resolution to this puzzle by revealing a seesaw effect in which the two hydrogen bonds of the diol are both longer than the single hydrogen bond in the ethoxy-ol. Semiclassical rate theory recovers the previously unexplained trends and leads to clear predictions regarding the relative H/D kinetic isotope effect (KIE) for ESIPT in the two systems. The theoretical KIE predictions are tested using ultrafast spectroscopy, confirming the seesaw effect. PMID- 27556888 TI - Congenital Adrenal Neuroblastoma With and Without Cystic Change: Differentiating Features With an Emphasis on the of Value of Ultrasound. AB - OBJECTIVE: The purpose of this study was to compare the features of congenital adrenal neuroblastomas with and without cystic changes and to emphasize the value of ultrasound in the diagnostic evaluation of cystic congenital adrenal neuroblastoma. MATERIALS AND METHODS: A total of 41 patients with surgically confirmed congenital adrenal neuroblastoma were enrolled. We divided the patients into two groups according to presence or absence of cystic change in the tumor, as determined from the initial ultrasound findings. Clinical and laboratory findings, disease stage, and patient outcome were investigated with a statistical comparison between the two groups. The imaging findings for cystic congenital adrenal neuroblastoma were reviewed to compare the additional diagnostic value of CT and MRI when paired with ultrasound. RESULTS: There were 22 patients (54%) in the group without cystic changes and 19 patients (46%) in the group with cystic changes. Prenatal detection and absence of metastasis were significantly more common in the cystic group than in the noncystic group (p < 0.05). Sensitivities of tumor marker levels were also significantly lower in the cystic group. Patient outcome was excellent, and there was no significant difference between the groups. With regard to imaging of cystic congenital adrenal neuroblastoma, in the 15 cases in which CT or MRI was paired with ultrasound, no additional diagnostic information was discerned with CT or MRI. CONCLUSION: Nearly one-half of congenital adrenal neuroblastomas are cystic, and these tumors have clinical and laboratory features that distinguish them from noncystic congenital adrenal neuroblastoma. Diagnostic tests, including CT, MRI, and assessment of tumor markers, have low diagnostic value in the evaluation of cystic congenital adrenal neuroblastoma. PMID- 27556890 TI - Abstracts of the 32nd International Conference on Pharmacoepidemiology & Therapeutic Risk Management, The Convention Centre Dublin, Dublin, Ireland August 25-28, 2016. PMID- 27556889 TI - Clinical pharmacology, drug-drug interactions and safety of pazopanib: a review. AB - INTRODUCTION: In the past decade, treatment options for metastatic renal cell carcinoma and soft-tissue sarcoma have expanded. Pazopanib was discovered during the screening of compounds that suppressed vascular endothelial growth factor receptor-2 (VEGFR-2). As other tyrosine kinase inhibitors (TKI), pazopanib is not totally specific for one target since it also inhibits stem-cell factor receptor (cKIT), platelet-derived growth factor receptors (PDGFRalpha, beta), VEGFR-1 and 3. Areas covered: Clinical pharmacology, drug-drug interactions and safety data published on pazopanib, between January 2006 and April 2016, are reviewed. Expert opinion: This new therapy has been shown to improve progression-free survival compared with previous approaches, in renal cell cancer and soft-tissue sarcoma. However, some specific sub-populations, such as elderly patients, patients with brain metastases or with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 or comorbidities, are poorly represented in pivotal pazopanib phase III studies. Pazopanib meets criteria defining therapies as candidates for therapeutic drug monitoring: large intra- and inter-patient pharmacokinetic variability, potential pharmacokinetic drug-drug interactions, pharmacokinetic/pharmacodynamic relationship and narrow therapeutic index. Knowledge of predictors that can be used to guide dosing regimens in the target population and in special populations needs to be improved. PMID- 27556892 TI - Economic analysis of pilot-scale production of B-phycoerythrin. AB - beta-Phycoerythrin is a color protein with several applications, from food coloring to molecular labeling. Depending on the application, different purity is required, affecting production cost and price. Different production and purification strategies for B-phycoerythrin have been developed, the most studied are based on the production using Porphyridium cruentum and purified using chromatographic techniques or aqueous two-phase systems. The use of the latter can result in a less expensive and intensive recovery of the protein, but there is lack of a proper economic analysis to study the effect of using aqueous two phase systems in a scaled-up process. This study analyzed the production of B Phycoerythrin using real data obtained during the scale-up of a bioprocess using specialized software (BioSolve, Biopharm Services, UK). First, a sensitivity analysis was performed to identify critical parameters for the production cost, then a Monte Carlo analysis to emulate real processes by adding uncertainty to the identified parameters. Next, the bioprocess was analyzed to determine its financial attractiveness and possible optimization strategies were tested and discussed. Results show that aqueous two-phase systems retain their advantages of low cost and intensive recovery (54.56%); the costs of production per gram calculated (before titer optimization: US$15,709 and after optimization: US$2,374) allowed to obtain profit (in the range of US$millions in a 10-year period) for a potential company taking this production method by comparing the production cost against commercial prices. The bioprocess analyzed is a promising and profitable method for the generation of a highly purified B-phycoerythrin. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1472 1479, 2016. PMID- 27556893 TI - Multifunctional Luminescent Porous Organic Polymer for Selectively Detecting Iron Ions and 1,4-Dioxane via Luminescent Turn-off and Turn-on Sensing. AB - The first case of selective Fe(3+) ions and 1,4-dioxane luminescent sensor based on a porous organic polymer, POP-HT, was synthesized by reaction of tetra(p aminophenyl)methane and chromophoric 2,5,8-trichloro-s-heptazine. POP-HT displayed prominent fluorescence quenching or enhancement in the presence of Fe(3+) ion or 1,4-dioxane. Moreover, an excellent linear relationship was established between luminescent intensity and the corresponding Fe(3+) ion or 1,4 dioxane concentration. The mechanisms of luminescence quenching and enhancement were also studied by both experiment and theoretical calculation. The results of this study suggest that POP-HT can work as an effective luminescent indicator for qualitative and quantitative detection of Fe(3+) ions and 1,4-dioxane in aqueous solution over other metal ions and organic solvents. PMID- 27556894 TI - Human Immunodeficiency Virus (HIV)-Infected Patients Accept Finger Stick Blood Collection for Point-Of-Care CD4 Testing. AB - INTRODUCTION: HIV-infected patients require antiretroviral treatment for life. To improve access to care, CD4 enumeration and viral load tests have been redesigned to be used as point-of-care techniques using finger-stick blood. Accurate CD4 counting in capillary blood requires a free flowing blood drop that is achieved by blade incision. The aim of this study was to assess the attitude of the patients toward blade-based finger-stick blood donation. METHODS: Four hundred and ninety-nine patients were included (299 patients from South Africa and 200 from Belgium). They completed a questionnaire to express their preference for finger stick or venipuncture, after undergoing both. The South African patient cohort was divided in two groups, receiving either single or multiple finger stick for CD4 and other HIV-related tests. The Belgian patients received a single finger stick for CD4 testing, and were asked to respond directly and again after two days. RESULTS: The majority of the patients preferred the finger stick to the venipuncture. The perceived pain using the blade was superior to a small needle, but similar to a large needle. They preferred up to three finger sticks over one venipuncture. Up to 30% of the patients changed their mind over two days. The main reason for choosing a finger stick was continued bleeding after venipuncture. The most cited objection to finger stick was pain/soreness. CONCLUSION: Patient perceptions support the implementation of donating capillary blood with blade-based finger stick during CD4 point-of-care testing. PMID- 27556895 TI - Polychaete Community of a Marine Protected Area along the West Coast of India Prior and Post the Tropical Cyclone, Phyan. AB - Tropical cyclones are extreme random meteorological events that can have profound implications to coastal biodiversities. Given that the frequency, intensity and duration of these events are poised to increase due to the global climate change, understanding the ecological impacts of such erratic occurrences becomes imperative to devise better management strategies. The eventful passage of the tropical cyclone, Phyan, along the northwestern coast of India in November 2009, coupled with the availability of historical data presented a rare opportunity to elucidate the consequences on the polychaete assemblages of the Malvan Marine Sanctuary and their subsequent recovery. This was achieved by comparison of the pre- and post-Phyan seasonal data from four different sites in and around the Sanctuary. MDS analyses and polychaete community parameters suggested conspicuous cyclone related effects on the polychaete community characteristics in the three outer stations off Malvan, whereas the relatively protected bay station remained more or less unscathed. Impacts, attributable to the cyclone apart from seasonal variations, included changes in polychaete composition, reductions in total polychaete density, species diversity, evenness and functional groups. Dominance of the opportunistic polychaete, Paraprionospiopatiens was all pervasive just after Phyan, resulting in poor diversity and evenness values. In the outer stations, diverse feeding modes present prior to the cyclone were replaced by microphagous feeders post the disturbance. However, the study also observed complete recovery as substantiated by the improvement inpolychaete density, diversity indices and re-instatement of multiple feeding guilds in affected areas. This resilience of the coastal waters off Malvan is attributed to its marine protected status, implying that reduced human interference aided rapid revival of damaged ecosystems. PMID- 27556896 TI - Saline irrigations following sinus surgery - a controlled, single blinded, randomized trial. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a common health problem. If medical treatment fails, endonasal sinus surgery is a valuable treatment option. A thorough postsurgical treatment is needed including, among others, nasal saline irrigations (NSI). In this prospective, controlled, single blinded, randomized trial, we aimed to evaluate efficacy of nasal saline irrigations following endonasal sinus surgery in CRS-patients with nasal polyps. METHODOLOGY: We examined patient's nasal symptoms, general quality of life and postoperative condition of the mucosa. We also investigated whether or not NSI reduced the number of missed workdays after surgery (MWD). Patients were randomized into an irrigation and non-irrigation arm. RESULTS: Following treatment, mean nasal sum score in the irrigation arm was 4.4 and in the non-irrigation arm it was 6.3. Accordingly, mean general sum-score in the irrigation arm was 2.5 and in the non irrigation arm 4.8. Thus, nasal irrigation led to a more pronounced improvement of nasal and general symptoms than in the non-irrigation arm. No differences were observed in postoperative condition of mucosa or number of MWD. CONCLUSIONS: Nasal irrigation improves symptoms score after ESS in patients with CRSwNP. PMID- 27556897 TI - Epidemiology of Methicillin-Resistant Staphylococcus aureus Diabetic Foot Infections in a Large Academic Hospital: Implications for Antimicrobial Stewardship. AB - INTRODUCTION: Diabetic foot infections (DFIs) are the leading cause of non traumatic lower extremity amputations in the United States. Antimicrobials active against methicillin-resistant Staphylococcus aureus (MRSA) are recommended in patients with associated risk factors; however, limited data exist to support these recommendations. Due to the changing epidemiology of MRSA, and the consequences of unnecessary antibiotic therapy, guidance regarding the necessity of empirical MRSA coverage in DFIs is needed. We sought to 1) describe the prevalence of MRSA DFIs at our institution and compare to the proportion of patients who receive MRSA antibiotic coverage and 2) identify risk factors for MRSA DFI. METHODS: This was a retrospective cohort study of all adult, culture positive DFI patients managed at University Hospital, San Antonio, TX between January 1, 2010 and September 1, 2014. Patient eligibility included a principal ICD-9-CM discharge diagnosis code for foot infection and a secondary diagnosis of diabetes. The primary outcome was MRSA identified in the wound culture. Independent variables assessed included patient demographics, comorbidities, prior hospitalization, DFI therapies, prior antibiotics, prior MRSA infection, and laboratory values. Multivariable logistic regression was used to identify risk factors for MRSA DFI. RESULTS: Overall, 318 patients met inclusion criteria. Patients were predominantly Hispanic (79%) and male (69%). Common comorbidities included hypertension (76%), dyslipidemia (52%), and obesity (49%). S. aureus was present in 46% of culture-positive DFIs (MRSA, 15%). A total of 273 patients (86%) received MRSA antibiotic coverage, resulting in 71% unnecessary use. Male gender (OR 3.09, 95% CI 1.37-7.99) and bone involvement (OR 1.93, 1.00-3.78) were found to be independent risk factors for MRSA DFI. CONCLUSIONS: Although MRSA was the causative pathogen in a small number of DFI, antibiotic coverage targeted against MRSA was unnecessarily high. PMID- 27556899 TI - Diffusion of CO2 in Large Crystals of Cu-BTC MOF. AB - Carbon dioxide adsorption in metal-organic frameworks has been widely studied for applications in carbon capture and sequestration. A critical component that has been largely overlooked is the measurement of diffusion rates. This paper describes a new reproducible procedure to synthesize millimeter-scale Cu-BTC single crystals using concentrated reactants and an acetic acid modulator. Microscopic images, X-ray diffraction patterns, Brunauer-Emmett-Teller surface areas, and thermogravimetric analysis results all confirm the high quality of these Cu-BTC single crystals. The large crystal size aids in the accurate measurement of micropore diffusion coefficients. Concentration-swing frequency response performed at varying gas-phase concentrations gives diffusion coefficients that show very little dependence on the loading up to pressures of 0.1 bar. The measured micropore diffusion coefficient for CO2 in Cu-BTC is 1.7 * 10(-9) m(2)/s. PMID- 27556898 TI - Embryonic Ethanol Exposure Dysregulates BMP and Notch Signaling, Leading to Persistent Atrio-Ventricular Valve Defects in Zebrafish. AB - Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3-24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/beta-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish. PMID- 27556900 TI - Nationwide Assessment of Trends in Choledocholithiasis Management in the United States From 1998 to 2013. AB - Importance: There are currently 2 widely accepted treatment strategies for patients presenting to the hospital with choledocholithiasis. However, the rate of use for each strategy in the United States has not been evaluated, and their trends over time have not been described. Furthermore, an optimal management strategy for choledocholithiasis has yet to be defined. Objective: To evaluate secular trends in the management of choledocholithiasis in the United States and to compare hospital length of stay between patients with choledocholithiasis treated with endoscopic retrograde cholangiopancreatography with laparoscopic cholecystectomy (ERCP+LC) vs laparoscopic common bile duct exploration with laparoscopic cholecystectomy (LCBDE+LC). Design, Setting, and Participants: In this cohort study, we studied patients with a primary diagnosis of choledocholithiasis that were included in the National Inpatient Sample between 1998 and 2013 from a representative sample of acute care hospitals in the United States. Patients with cholangitis or pancreatitis were excluded. Main Outcomes and Measures: Unadjusted and risk-adjusted median hospital length of stay. Results: Of the 37 207 patients included in our analysis, 36 048 (96.9%) were treated with ERCP+LC and 1159 (3.1%) were treated with LCBDE+LC. The mean (SD) age of patients treated with ERCP+LC was 50.7 (21.1) years and was 51.9 (20.9) years for those treated with LCBDE+LC; 25 788 (69.3%) were female. Analysis of the National Inpatient Sample data indicates that there are an average of 26 158 patients with choledocholithiasis admitted in the United States each year. The overall use of CBDE for patients with choledocholithiasis decreased from 39.8% of admissions in 1998 to 8.5% in 2013 (P < .001). A decrease was also seen for open CBDE (30.6% vs 5.5%; P < .001) and laparoscopic CBDE (9.2% vs 3.0%; P < .001) independently. Rates of management with LCBDE+LC decreased from 5.3% to 1.5% (P < .001), while rates of ERCP+LC increased from 52.8% to 85.7% (P < .001). The unadjusted median hospital length of stay was shorter for patients treated with LCBDE+LC than for those treated with ERCP+LC (3.0 vs 4.0 days; P < .001). After risk-adjustment, the median length of stay remained 0.5 days shorter for patients treated with LCBDE+LC than with ERCP+LC (3.5 vs 4.0 days; P < .001). Conclusions and Relevance: This study highlights the marked decline in the use of both open and laparoscopic CBDE in the United States as well as the benefit to the length of stay LCBDE+LC has over ERCP+LC. Despite a persistent need for CBDE and the potential benefits of LCBDE+LC over ERCP+LC for managing choledocholithiasis, if current trends continue, CBDE may be at risk of disappearing from the surgical armamentarium. PMID- 27556901 TI - Origin of the Absorption Band of Bromophenol Blue in Acidic and Basic pH: Insight from a Combined Molecular Dynamics and TD-DFT/MM Study. AB - We study the linear and nonlinear optical properties of a well-known acid-base indicator, bromophenol blue (BPB), in aqueous solution by employing static and integrated approaches. In the static approach, optical properties have been calculated using time-dependent density functional theory (TD-DFT) on the fully relaxed geometries of the neutral and different unprotonated forms of BPB. Moreover, both closed and open forms of BPB were considered. In the integrated approach, the optical properties have been computed over many snapshots extracted from molecular dynamics simulation using a hybrid time-dependent density functional theory/molecular mechanics approach. The static approach suggests closed neutral => anionic interconversion as the dominant mechanism for the red shift in the absorption spectra of BPB due to a change from acidic to basic pH. It is found by employing an integrated approach that the two interconversions, namely open neutral => anionic and open neutral => dianionic, can contribute to the pH-dependent shift in the absorption spectra of BPB. Even though both static and integrated approaches reproduce the pH-dependent red shift in the absorption spectra of BPB, the latter one is suitable to determine both the spectra and spectral broadening. Finally, the computed static first hyperpolarizability for various protonated and deprotonated forms of BPB reveals that this molecule can be used as a nonlinear optical probe for pH sensing in addition to its highly exploited use as an optical probe. PMID- 27556902 TI - Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2' Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase eta. AB - The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymerase eta (hPol eta). Here, we report the crystal structure of a ternary Pol?DNA?dCTP complex between a C8-dG ABA-containing template:primer duplex and hPol eta. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP. PMID- 27556904 TI - Catalytic Properties of AgPt Nanoshells as a Function of Size: Larger Outer Diameters Lead to Improved Performances. AB - We report herein a systematic investigation on the effect of the size of silver (Ag) nanoparticles employed as starting materials over the morphological features and catalytic performances of AgPt nanoshells produced by a combination of galvanic replacement between Ag and PtCl6(2-) and PtCl6(2-) reduction by hydroquinone. More specifically, we focused on Ag nanoparticles of four different sizes as starting materials, and found that the outer diameter, shell thickness, and the number of Pt surface atoms of the produced nanoshells increased with the size of the starting Ag nanoparticles. The produced AgPt nanoshells were supported into SiO2, and the catalytic performances of the AgPt/SiO2 nanocatalysts toward the gas-phase oxidation of benzene, toluene, and o-xylene (BTX oxidation) followed the order: AgPt 163 nm/SiO2 > AgPt 133 nm/SiO2 > AgPt 105 nm/SiO2 > AgPt 95 nm/SiO2. Interestingly, bigger AgPt nanoshell sizes lead to better catalytic performances in contrast to the intuitive prediction that particles having larger outer diameters tend to present poorer catalytic activities due to their lower surface to volume ratios as compared to smaller particles. This is in agreement with the H2 chemisorption results, and can be assigned to the increase in the Pt surface area with size due to the presence of smaller NPs islands at the surface of the nanoshells having larger outer diameters. This result indicates that, in addition to the overall diameters, the optimization of the surface morphology may play an important role over the optimization of catalytic activities in metal-based nanocatalysts, which can be even more pronounced that the size effect. Our data demonstrate that the control over surface morphology play a very important role relative to the effect of size to the optimization of catalytic performances in catalysts based on noble-metal nanostructures. PMID- 27556905 TI - Job strain and informal caregiving as predictors of long-term sickness absence: A longitudinal multi-cohort study. AB - Objectives The aim of this study was to investigate the individual, joint and interactive effects of job strain and informal caregiving on long-term sickness absence with special attention to gender differences. Methods The study comprised a prospective cohort study of 6798 working adults from France, 14 727 from Finland, and 5275 from the UK. A total of 26 800 participants, age 52 (interquartile range 47-56) years participated in the study. Job strain was assessed using the demand-control model. Informal caregiving was defined as care for a sick, disabled, or elderly person. Long-term sickness absence spells defined as absence >14 consecutive days were registered during two years follow up. We used recurrent-events Cox regression in random-effects meta-analyses. Results A total of 12% men and 21% women had >=1 long-term sickness absence spell. Among women, both high job strain [hazard ratio (HR) 1.08, 95% confidence interval (95% CI) 1.00-1.17] and informal caregiving (HR 1.13, 95% CI 1.04-1.23) were associated with a modestly higher risk of sickness absence. Women doubly exposed to high job strain and informal caregiving also showed a moderately higher risk of sickness absence (HR 1.20, 95% CI 1.03-1.41), but the excess risk was not more than expected from joint exposure to caregiving and job strain. Neither job strain nor informal caregiving predicted sickness absence for men. Conclusions High job strain and informal caregiving predicted long-term sickness absence among women. However there was no noticeable interaction in the presence of both exposures. PMID- 27556906 TI - Low Defect FeFe(CN)6 Framework as Stable Host Material for High Performance Li Ion Batteries. AB - Low cost and high performance Li-ion batteries have been extensively pursued for grid-scale energy storage applications; however, their development has been impeded for a long time due to the lack of qualified cathode materials with not only decent electrochemical performance but also resource abundance and low price. In this paper, we report Prussian-blue type FeFe(CN)6 nanocrystals with well-controlled lattice defects and perfect nanocubic morphology, which can exhibit a high Li-storage capacity of 160 mAh g(-1), a strong rate performance at 24 C, and a superior cycle stability with 90% capacity retention over 300 cycles. This low defect lattice and its excellent Li-insertion performance might provide a new insight into the design of advanced Li-ion battery materials and also a competitive alternative to the presently developed Li(+) insertion cathodes to develop low cost and high performance Li-ion batteries for grid-scale energy storage applications. PMID- 27556907 TI - Effect of Drug Interactions and Adherence on Coagulation Control of Patients Treated With Warfarin. PMID- 27556908 TI - Is There a Relationship Between Speech Identification in Noise and Categorical Perception in Children With Dyslexia? AB - PURPOSE: Children with dyslexia have been suggested to experience deficits in both categorical perception (CP) and speech identification in noise (SIN) perception. However, results regarding both abilities are inconsistent, and the relationship between them is still unclear. Therefore, this study aimed to investigate the relationship between CP and the psychometric function of SIN perception. METHOD: Sixteen children with dyslexia, 16 chronological-age controls, and 16 reading-level controls were evaluated in CP of a voicing continuum and in consonant identification in both stationary and fluctuating noises. RESULTS: There was a small but significant impairment in speech identification performance of children with dyslexia in stationary noise compared with chronological age-matched controls (but not reading level-matched controls). However, their performance increased in a fluctuating background, hence suggesting normal masking and unmasking effects and preserved sensory processing of speech information. Regarding CP, location of the phoneme boundary differed in the children with dyslexia compared with both control groups. However, scrutinizing individual profiles failed to reveal consistently poor performance in SIN and CP tasks. In addition, there was no significant correlation between CP, SIN perception, and reading scores in the group with dyslexia. CONCLUSIONS: The relationship between the SIN deficit and CP, and how they potentially affect reading in children with dyslexia, remains unclear. However, these results are inconsistent with the notion that children with dyslexia suffer from a low-level temporal processing deficit and rather suggest a role of nonsensory (e.g., attentional) factors in their speech perception difficulties. PMID- 27556909 TI - ACUTE MACULAR NEURORETINOPATHY AFTER RANIBIZUMAB INJECTION IN A DIABETIC PATIENT. AB - PURPOSE: To report a case of acute macular neuroretinopathy occurring after intravitreal ranibizumab injection for diabetic macular edema. METHODS: Observational clinical case report. RESULTS: The patient received an intravitreal ranibizumab (0.3 mg) injection for diabetic macular edema. Three days later, he had a decline in vision associated with a central and paracentral scotoma. Optical coherence tomography (OCT) demonstrated bandlike hyperreflectivity of the outer nuclear and plexiform layers corresponding to the patient's scotoma, consistent with the diagnosis of acute macular neuroretinopathy. There was spontaneous resolution of the abnormalities observed in optical coherence tomography, but only partial resolution of the scotoma was observed 4 months after presentation. CONCLUSION: Diabetic retinopathy may be associated with acute macular neuroretinopathy. The temporal relationship between ranibizumab injection and the onset of acute macular neuroretinopathy in this case report raises the possibility of a causal relationship. PMID- 27556910 TI - Screening and Identification of Highly Specific MAbs for Discovering Novel Biomarkers of Bone Marrow Stromal Cells. AB - Bone marrow stromal cells (BMSCs) are very useful model systems for a better understanding of cell behavior and differential gene expression. Up to now, there have not been specific markers and MAbs for BMSCs that hamper the identification and isolation of BMSCs populations. In this study, chicken BMSCs were isolated from 1-day-old Beijing fatty chickens by adherent culture. After biological characteristics were detected, the chicken BMSCs were used to immunize BALB/c mice to prepare BMSCs-specific monoclonal antibodies (MAbs) by the routine hybridoma technique. These MAbs were characterized by FACS analysis, immunocytochemistry, immunohistochemistry, subtype identification, and Western blotting assay and were used to explore markers of chicken BMSCs. Our data showed that BMSCs expressing antigens CD29, CD44, and CD105, but not expressing antigens CD34, CD45, and CD11b, could be isolated from postnatal chicken bone marrow and hold great potential for multiline age differentiation. Meanwhile, we obtained two hybridoma cell lines secreting chicken BMSCs-specific MAbs (named CHK1 and CHK2), which specifically recognized the surface antigens expressed on chicken BMSCs. According to our subtype identification, heavy chains of CHK1 and CHK2 were typed as IgG1 and IgG2b, respectively; all the light strands were kappa subtype. MAbs CHK1 and CHK2 can be used to develop the detection assay and to discover novel biomarkers of chicken BMSCs. PMID- 27556911 TI - Characterization and Selection of 3-(1-Naphthoyl)-Indole Derivative-Specific Alpaca VHH Antibodies Using a Phage Display Library. AB - A new alpaca VHH antibody library against 3-(1-naphthoyl)-indole derivatives was developed from alpaca immunized with 7-(3-(1-naphthoyl)-1H-indol-1-yl)-heptanoic acid-keyhole limpet hemocyanin (Hep-KLH) protein conjugates as the immunogen. From this library, two 3-(1-naphthoyl)-indole derivative-specific clones, named NN01 and NN02, were isolated using biopanning technology. The binding specificity of these clones was confirmed using a competitive enzyme-linked immunosorbent assay (c-ELISA). Based on the results of c-ELISA, a median inhibitory concentration (IC50) of these two VHH antibodies, NN01 and NN02, in the case of 7 (3-(1-naphthoyl)-1H-indol-1-yl)-heptanoic acid (Hep; one of 3-(1-naphthoyl) indole derivatives) as an inhibitor exhibited an approximate 3 * 10(-7) M and 6 * 10(-7) M, respectively. Thus, VHH antibodies produced in this study could be considered a useful tool for the detection of 3-(1-naphthoyl)-indole derivatives. PMID- 27556912 TI - Monoclonal Antibodies DSHB-hGAPDH-2G7 and DSHB-hGAPDH-4B7 Against Human Glyceraldehyde-3-Phosphate Dehydrogenase. PMID- 27556913 TI - Antihuman Cardiac Troponin I (hcTn I) Monoclonal Antibody. PMID- 27556914 TI - Monoclonal Antibody Against Porcine Circovirus2 Cap Protein. PMID- 27556915 TI - Reaction rates in a theory of mechanochemical pathways. AB - If one applies mechanical stress to a molecule in a defined direction then one generates a new, effective potential energy surface (PES). Changes for minima and saddle points (SP) by the stress are described by Newton trajectories on the original PES (Quapp and Bofill, Theor. Chem. Acc. 2016, 135, 113). The barrier of a reaction fully breaks down for the maximal value of the norm of the gradient of the PES along a pulling Newton trajectory. This point is named barrier breakdown point (BBP). Depending on the pulling direction, different reaction pathways can be enforced. If the exit SP of the chosen pulling direction is not the lowest SP of the reactant valley, on the original PES, then the SPs must change their role anywhere: in this case the curve of the log(rate) over the pulling force of a forward reaction can show a deviation from the normal concave curvature. We discuss simple, two-dimensional examples for this model to understand more deeply the mechanochemistry of molecular systems under a mechanical stress. (c) 2016 Wiley Periodicals, Inc. PMID- 27556917 TI - Mean glandular doses in mammography: a comparison of values displayed by a mammography unit with in-house values, both using the method proposed by Dance. AB - The purpose of this work is to compare the mean glandular dose (MGD) displayed by the mammography system and the MGD calculated according to the method proposed by Dance for women. This study also attempts to analyse whether the relationship between the calculated and the displayed values is constant and what factors influence this relationship. Material for this study included data from 1200 exposures (i.e. six series; each series consisting of 200 exposures) performed with one full-field digital mammography unit. Based on collected parameters of exposures, values of the MGD for individual mammography examinations were calculated according to the methods proposed by Dance. Obtained values of the MGD were compared with the values displayed by the mammography system. The MGD displayed by the mammography system and the MGD calculated according to the method proposed by Dance for women are significantly different. This result emphasises the importance of verifying MGD values for patient radiation protection, particularly after machine servicing. PMID- 27556916 TI - Lung cancer among native and foreign-born Swedes: histopathology, treatment, and survival. AB - BACKGROUND: Lung cancer (LC) is the leading cause of cancer-related death worldwide, including Sweden. Several studies have shown that socioeconomic status affects the risk, treatment, and survival of LC. Due to immigration after Second World War, foreign-born people constitute 12.5% of the Swedish population. We wanted to investigate if there were any differences in LC management, treatment and survival among the foreign-born Swedes (FBS) compared to the native Swedish population (NatS) in Stockholm. MATERIAL AND METHODS: A retrospective analysis of all patients diagnosed with non-small cell lung cancer (NSCLC) at the Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Solna from 1 January 2003 to 31 December 2008 was made. In all, 2041 cases of LC were diagnosed, thereof 1803 with NSCLC. Of these, 211 (11.7%) were FBS. RESULTS: The mean age of NatS and FBS patients was 69.9 years, median 70 (range 26-96) and 66.0 years, median 66 (range 38-94), respectively (p < 0.001). In all, 89.8% of NatS and 90.0% of FBS were either smokers or former smokers. Adenocarcinoma was the most common subtype in both groups (NatS 54.7%, FBS 48.3%). In 140 (8.8%) of the NatS and 17 (8.1%) of the FBS the diagnosis was clinical only. There were no significant differences in stage at diagnosis, nor in performance status (PS) or different therapies between the groups. The median overall survival time for the NatS was 272 days and for FBS 328 days, again no significant difference. However, the median overall survival time for female NatS was 318 days and for female FBS 681 days (p = 0.002). CONCLUSION: FBS patients were significantly younger than NatS at diagnosis, and female FBS lived longer than female NatS, but otherwise there were no significant differences between NatS and FBS patients with LC regarding diagnosis, treatment, and survival. PMID- 27556918 TI - Masking in reports of "most serious" events: bias in estimators of sports injury incidence in Canadian children. AB - INTRODUCTION: Surveys that collect information on injuries often focus on the single "most serious" event to help limit recall error and reduce survey length. However, this can mask less serious injuries and result in biased incidence estimates for specific injury subcategories. METHODS: Data from the 2002 Health Behaviour in School-aged Children (HBSC) survey and from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were used to compare estimates of sports injury incidence in Canadian children. RESULTS: HBSC data indicate that 6.7% of children report sustaining a sports injury that required an emergency department (ED) visit. However, details were only collected on a child's "most serious" injury, so children who had multiple injuries requiring an ED visit may have had sports injuries that went unreported. The rate of 6.7% can be seen to be an underestimate by as much as 4.3%. Corresponding CHIRPP surveillance data indicate an incidence of 9.9%. Potential masking bias is also highlighted in our analysis of injuries attended by other health care providers. CONCLUSION: The "one most serious injury" line of questioning induces potentially substantial masking bias in the estimation of sports injury incidence, which limits researchers' ability to quantify the burden of sports injury. Longer survey recall periods naturally lead to greater masking. The design of future surveys should take these issues into account. In order to accurately inform policy decisions and the direction of future research, researchers must be aware of these limitations. PMID- 27556919 TI - Health behaviours associated with indoor tanning based on the 2012/13 Manitoba Youth Health Survey. AB - INTRODUCTION: Although indoor tanning causes cancer, it remains relatively common among adolescents. Little is known about indoor tanning prevalence and habits in Canada, and even less about associated behaviours. This study explores the prevalence of adolescent indoor tanning in Manitoba and its association with other demographic characteristics and health behaviours. METHODS: We conducted secondary analyses of the 2012/13 Manitoba Youth Health Survey data collected from Grade 7 to 12 students (n = 64 174) and examined associations between indoor tanning (whether participants had ever used artificial tanning equipment) and 25 variables. Variables with statistically significant associations to indoor tanning were tested for collinearity and grouped based on strong associations. For each group of highly associated variables, the variable with the greatest effect upon indoor tanning was placed into the final logistic regression model. Separate analyses were conducted for males and females to better understand sex based differences, and analyses were adjusted for age. RESULTS: Overall, 4% of male and 9% of female students reported indoor tanning, and prevalence increased with age. Relationships between indoor tanning and other variables were similar for male and female students. Binary logistic regression models indicated that several variables significantly predicted indoor tanning, including having part time work, being physically active, engaging in various risk behaviours such as driving after drinking for males and unplanned sex after alcohol/drugs for females, experiencing someone say something bad about one's body shape/size/appearance, identifying as trans or with another gender, consuming creatine/other supplements and, for females only, never/rarely using sun protection. CONCLUSION: Indoor tanning among adolescents was associated with age, part-time work, physical activity and many consumption behaviours and lifestyle risk factors. Though legislation prohibiting adolescent indoor tanning is critical, health promotion to discourage indoor tanning may be most beneficial if it also addresses these associated factors. PMID- 27556920 TI - Patterns of multiple health risk-behaviours in university students and their association with mental health: application of latent class analysis. AB - INTRODUCTION: University and college campuses may be the last setting where it is possible to comprehensively address the health of a large proportion of the young adult population. It is important that health promoters understand the collective challenges students are facing, and to better understand the broader lifestyle behavioural patterning evident during this life stage. The purpose of this study was to examine the clustering of modifiable health-risk behaviours and to explore the relationship between these identified clusters and mental health outcomes among a large Canadian university sample. METHODS: Undergraduate students (n = 837; mean age = 21 years) from the University of Toronto completed the National College Health Assessment survey. The survey consists of approximately 300 items, including assessments of student health status, mental health and health-risk behaviours. Latent class analysis was used to identify patterning based on eight salient health-risk behaviours (marijuana use, other illicit drug use, risky sex, smoking, binge drinking, poor diet, physical inactivity, and insufficient sleep). RESULTS: A three-class model based on student behavioural patterns emerged: "typical," "high-risk" and "moderately healthy." Results also found high-risk students reporting significantly higher levels of stress than typical students (chi2(1671) = 7.26, p < .01). CONCLUSION: Students with the highest likelihood of engaging in multiple health-risk behaviours reported poorer mental health, particularly as it relates to stress. Although these findings should be interpreted with caution due to the 28% response rate, they do suggest that interventions targeting specific student groups with similar patterning of multiple health-risk behaviours may be needed. PMID- 27556921 TI - Chronic Disease and Injury Indicator Framework: Quick Stats, 2016 Edition. PMID- 27556922 TI - An integrative genomics approach for identifying novel functional consequences of PBRM1 truncated mutations in clear cell renal cell carcinoma (ccRCC). AB - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Recent large-scale next-generation sequencing analyses reveal that PBRM1 is the second most frequently mutated gene harboring many truncated mutations and has a suspected tumor suppressor role in ccRCC. However, the biological consequences of PBRM1 somatic mutations (e.g., truncated mutations) that drive tumor progression in ccRCC remain unclear. METHODS: In this study, we proposed an integrative genomics approach to explore the functional consequences of PBRM1 truncated mutations in ccRCC by incorporating somatic mutations, mRNA expression, DNA methylation, and microRNA (miRNA) expression profiles from The Cancer Genome Atlas (TCGA). We performed a systematic analysis to detect the differential molecular features in a total of 11 ccRCC samples harboring PBRM1 truncated mutations from the 33 "pan-negative" ccRCC samples. We excluded the samples that had any of the five high-confidence driver genes (VHL, BAP1, SETD2, PTEN and KDM5C) reported in ccRCC to avoid their possible influence in our results. RESULTS: We identified 613 differentially expressed genes (128 up regulated and 485 down-regulated genes using cutoff |log2FC| > 1 and p < 0.05) in PBRM1 mutated group versus "pan-negative" group. The gene function enrichment analysis revealed that down-regulated genes were significantly enriched in extracellular matrix organization (adjusted p = 2.05 * 10(-7)), cell adhesion (adjusted p = 2.85 * 10(-7)), and ion transport (adjusted p = 9.97 * 10(-6)). Surprisingly, 26 transcriptional factors (TFs) genes including HOXB9, PAX6 and FOXC1 were found to be significantly differentially expressed (23 over expressed TFs and three lower expressed TFs) in PBRM1 mutated group compared with "pan negative" group. In addition, we identified 1405 differentially methylated CpG sites (targeting 1308 genes, ||log2FC| > 1, p < 0.01) and 185 significantly altered microRNAs (|log2FC| > 1, p < 0.05) associated with truncated PBRM1 mutations. Our integrative analysis suggested that methylation and miRNA alterations were likely the downstream events associated with PBRM1 truncation mutations. CONCLUSIONS: In summary, this study provided some important insights into the understanding of tumorigenesis driven by PBRM1 truncated mutations in ccRCC. The approach may be applied to many driver genes in various cancers. PMID- 27556923 TI - MBDDiff: an R package designed specifically for processing MBDcap-seq datasets. AB - BACKGROUND: Since its initial discovery in 1975, DNA methylation has been intensively studied and shown to be involved in various biological processes, such as development, aging and tumor progression. Many experimental techniques have been developed to measure the level of DNA methylation. Methyl-CpG binding domain-based capture followed by high-throughput sequencing (MBDCap-seq) is a widely used method for characterizing DNA methylation patterns in a genome-wide manner. However, current methods for processing MBDCap-seq datasets does not take into account of the region-specific genomic characteristics that might have an impact on the measurements of the amount of methylated DNA (signal) and background fluctuation (noise). Thus, specific software needs to be developed for MBDCap-seq experiments. RESULTS: A new differential methylation quantification algorithm for MBDCap-seq, MBDDiff, was implemented. To evaluate the performance of the MBDDiff algorithm, a set of simulated signal based on negative binomial and Poisson distribution with parameters estimated from real MBDCap-seq datasets accompanied with different background noises were generated, and then performed against a set of commonly used algorithms for MBDCap-seq data analysis in terms of area under the ROC curve (AUC), number of false discoveries and statistical power. In addition, we also demonstrated the effective of MBDDiff algorithm to a set of in-house prostate cancer samples, endometrial cancer samples published earlier, and a set of public-domain triple negative breast cancer samples to identify potential factors that contribute to cancer development and recurrence. CONCLUSIONS: In this paper we developed an algorithm, MBDDiff, designed specifically for datasets derived from MBDCap-seq. MBDDiff contains three modules: quality assessment of datasets and quantification of DNA methylation; determination of differential methylation of promoter regions; and visualization functionalities. Simulation results suggest that MBDDiff performs better compared to MEDIPS and DESeq in terms of AUC and the number of false discoveries at different levels of background noise. MBDDiff outperforms MEDIPS with increased backgrounds noise, but comparable performance when noise level is lower. By applying MBDDiff to several MBDCap-seq datasets, we were able to identify potential targets that contribute to the corresponding biological processes. Taken together, MBDDiff provides user an accurate differential methylation analysis for data generated by MBDCap-seq, especially under noisy conditions. PMID- 27556924 TI - Detection of high variability in gene expression from single-cell RNA-seq profiling. AB - BACKGROUND: The advancement of the next-generation sequencing technology enables mapping gene expression at the single-cell level, capable of tracking cell heterogeneity and determination of cell subpopulations using single-cell RNA sequencing (scRNA-seq). Unlike the objectives of conventional RNA-seq where differential expression analysis is the integral component, the most important goal of scRNA-seq is to identify highly variable genes across a population of cells, to account for the discrete nature of single-cell gene expression and uniqueness of sequencing library preparation protocol for single-cell sequencing. However, there is lack of generic expression variation model for different scRNA seq data sets. Hence, the objective of this study is to develop a gene expression variation model (GEVM), utilizing the relationship between coefficient of variation (CV) and average expression level to address the over-dispersion of single-cell data, and its corresponding statistical significance to quantify the variably expressed genes (VEGs). RESULTS: We have built a simulation framework that generated scRNA-seq data with different number of cells, model parameters, and variation levels. We implemented our GEVM and demonstrated the robustness by using a set of simulated scRNA-seq data under different conditions. We evaluated the regression robustness using root-mean-square error (RMSE) and assessed the parameter estimation process by varying initial model parameters that deviated from homogeneous cell population. We also applied the GEVM on real scRNA-seq data to test the performance under distinct cases. CONCLUSIONS: In this paper, we proposed a gene expression variation model that can be used to determine significant variably expressed genes. Applying the model to the simulated single cell data, we observed robust parameter estimation under different conditions with minimal root mean square errors. We also examined the model on two distinct scRNA-seq data sets using different single-cell protocols and determined the VEGs. Obtaining VEGs allowed us to observe possible subpopulations, providing further evidences of cell heterogeneity. With the GEVM, we can easily find out significant variably expressed genes in different scRNA-seq data sets. PMID- 27556925 TI - HIV Screening Rates among Medicaid Enrollees Diagnosed with Other Sexually Transmitted Infections. AB - INTRODUCTION: Approximately 20 million new sexually transmitted infections (STIs) are diagnosed yearly in the United States costing the healthcare system an estimated $16 billion in direct medical expenses. The presence of other STIs increases the risk of HIV transmission. The Centers for Disease Control and Prevention (CDC) has long recommended routine HIV screening for individuals with a diagnosed STI. Unfortunately, HIV screening prevalence among STI diagnosed patients are still sub-optimal in many healthcare settings. OBJECTIVE: To determine the proportion of STI-diagnosed persons in the Medicaid population who are screened for HIV, examine correlates of HIV screening, and to suggest critical intervention points to increase HIV screening in this population. METHODS: A retrospective database analysis was conducted to examine the prevalence and correlates of HIV screening among participants. Participant eligibility was restricted to Medicaid enrollees in 29 states with a primary STI diagnosis (chlamydia, gonorrhea, and syphilis) or pelvic inflammatory disease claim in 2009. HIV-positive persons were excluded from the study. Frequencies and descriptive statistics were conducted to characterize the sample in general and by STI diagnosis. Univariate and multivariate logistic regression were performed to estimate unadjusted odds ratios and adjusted odds ratio respectively and the 95% confidence intervals. Multivariate logistic regression models that included the independent variables (race, STI diagnosis, and healthcare setting) and covariates (gender, residential status, age, and state) were analyzed to examine independent associations with HIV screening. RESULTS: About 43% of all STI diagnosed study participants were screened for HIV. STI-diagnosed persons that were between 20-24 years, female, residing in a large metropolitan area and with a syphilis diagnosis were more likely to be screened for HIV. Participants who received their STI diagnosis in the emergency department were less likely to be screened for HIV than those diagnosed in a physician's office. CONCLUSION: This study showed that HIV screening prevalence among persons diagnosed with an STI are lower than expected based on the CDC's recommendations. These suboptimal HIV screening prevalence present "missed opportunities" for HIV screening in at-risk populations. Measures and incentives to increase HIV screening among all STI diagnosed persons are vital to the timely identification of HIV infection, linkage to HIV care, and mitigating further HIV transmission. PMID- 27556926 TI - Evolution of the Twist Subfamily Vertebrate Proteins: Discovery of a Signature Motif and Origin of the Twist1 Glycine-Rich Motifs in the Amino-Terminus Disordered Domain. AB - Twist proteins belong to the basic helix-loop-helix (bHLH) family of multifunctional transcriptional factors. These factors are known to use domains other than the common bHLH in protein-protein interactions. There has been much work characterizing the bHLH domain and the C-terminus in protein-protein interactions but despite a few attempts more focus is needed at the N-terminus. Since the region of highest diversity in Twist proteins is the N-terminus, we analyzed the conservation of this region in different vertebrate Twist proteins and study the sequence differences between Twist1 and Twist2 with emphasis on the glycine-rich regions found in Twist1. We found a highly conserved sequence motif in all Twist1 (SSSPVSPADDSLSNSEEE) and Twist2 (SSSPVSPVDSLGTSEEE) mammalian species with unknown function. Through sequence comparison we demonstrate that the Twist protein family ancestor was "Twist2-like" and the two glycine-rich regions found in Twist1 sequences were acquired late in evolution, apparently not at the same time. The second glycine-rich region started developing first in the fish vertebrate group, while the first glycine region arose afterwards within the reptiles. Disordered domain and secondary structure predictions showed that the amino acid sequence and disorder feature found at the N-terminus is highly evolutionary conserved and could be a functional site that interacts with other proteins. Detailed examination of the glycine-rich regions in the N-terminus of Twist1 demonstrate that the first region is completely aliphatic while the second region contains some polar residues that could be subject to post-translational modification. Phylogenetic and sequence space analysis showed that the Twist1 subfamily is the result of a gene duplication during Twist2 vertebrate fish evolution, and has undergone more evolutionary drift than Twist2. We identified a new signature motif that is characteristic of each Twist paralog and identified important residues within this motif that can be used to distinguish between these two paralogs, which will help reduce Twist1 and Twist2 sequence annotation errors in public databases. PMID- 27556928 TI - Cold Shock Proteins Are Expressed in the Retina Following Exposure to Low Temperatures. AB - Hypothermia has been proposed as a therapeutic intervention for some retinal conditions, including ischemic insults. Cold exposure elevates expression of cold shock proteins (CSP), including RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding protein (CIRP), but their presence in mammalian retina is so far unknown. Here we show the effects of hypothermia on the expression of these CSPs in retina-derived cell lines and in the retina of newborn and adult rats. Two cell lines of retinal origin, R28 and mRPE, were exposed to 32 degrees C for different time periods and CSP expression was measured by qRT-PCR and Western blotting. Neonatal and adult Sprague-Dawley rats were exposed to a cold environment (8 degrees C) and expression of CSPs in their retinas was studied by Western blotting, multiple inmunofluorescence, and confocal microscopy. RBM3 expression was upregulated by cold in both R28 and mRPE cells in a time-dependent fashion. On the other hand, CIRP was upregulated in R28 cells but not in mRPE. In vivo, expression of CSPs was negligible in the retina of newborn and adult rats kept at room temperature (24 degrees C). Exposure to a cold environment elicited a strong expression of both proteins, especially in retinal pigment epithelium cells, photoreceptors, bipolar, amacrine and horizontal cells, Muller cells, and ganglion cells. In conclusion, CSP expression rapidly rises in the mammalian retina following exposure to hypothermia in a cell type-specific pattern. This observation may be at the basis of the molecular mechanism by which hypothermia exerts its therapeutic effects in the retina. PMID- 27556927 TI - Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum. AB - Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient's clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-gamma and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease. PMID- 27556929 TI - Knowledge, Beliefs and Attitudes of Patients and the General Public towards the Interactions of Physicians with the Pharmaceutical and the Device Industry: A Systematic Review. AB - OBJECTIVE: To systematically review the evidence on the knowledge, beliefs, and attitudes of patients and the general public towards the interactions of physicians with the pharmaceutical and the device industry. METHODS: We included quantitative and qualitative studies addressing any type of interactions between physicians and the industry. We searched MEDLINE and EMBASE in August 2015. Two reviewers independently completed data selection, data extraction and assessment of methodological features. We summarized the findings narratively stratified by type of interaction, outcome and country. RESULTS: Of the 11,902 identified citations, 20 studies met the eligibility criteria. Many studies failed to meet safeguards for protecting from bias. In studies focusing on physicians and the pharmaceutical industry, the percentages of participants reporting awareness was higher for office-use gifts relative to personal gifts. Also, participants were more accepting of educational and office-use gifts compared to personal gifts. The findings were heterogeneous for the perceived effects of physician-industry interactions on prescribing behavior, quality and cost of care. Generally, participants supported physicians' disclosure of interactions through easy-to read printed documents and verbally. In studies focusing on surgeons and device manufacturers, the majority of patients felt their care would improve or not be affected if surgeons interacted with the device industry. Also, they felt surgeons would make the best choices for their health, regardless of financial relationship with the industry. Participants generally supported regulation of surgeon-industry interactions, preferably through professional rather than governmental bodies. CONCLUSION: The awareness of participants was low for physicians' receipt of personal gifts. Participants also reported greater acceptability and fewer perceived influence for office-use gifts compared to personal gifts. Overall, there appears to be lower awareness, less concern and more acceptance of surgeon-device industry interactions relative to physician pharmaceutical industry interactions. We discuss the implications of the findings at the patient, provider, organizational, and systems level. PMID- 27556930 TI - The potential of targeting epigenetic regulators for the treatment of fibrotic cardiac diseases. PMID- 27556931 TI - Randomized Controlled Trial to Assess the Effectiveness of a Self-Care Program for Pregnant Women for Relieving Hiesho. AB - OBJECTIVE: To assess differences in improvement of hiesho (sensitivity to cold) through a randomized controlled trial (RCT) of one group that used a self-care program (the Home Care Package Program for Relieving Hiesho) and another that did not. METHODS: Participants were pregnant women experiencing hiesho in the 28th to 33rd weeks of pregnancy. The group carried out the intervention program for 4 weeks by wearing leg warmers, performing exercises, and pressing acupuncture points. The control group did not take any specific actions. Hiesho condition was assessed by using thermography to measure temperature in the four limbs; the changes were analyzed. RESULTS: Findings for 140 pregnant women (73 in the experimental group and 67 in the control group) were analyzed. Participants' body temperatures were measured after completion of the program for 4 weeks and compared to their temperatures before start of the program. Compared with the control group, the experimental group had arm skin temperature 3.0 degrees C (p < 0.001) higher and leg skin temperature 1.93 degrees C (p = 0.02) higher; both differences were significant. CONCLUSION: The Home Care Package Program for Relieving Hiesho self-care program significantly relieved hiesho. PMID- 27556932 TI - Shining Light on Copper: Unique Opportunities for Visible-Light-Catalyzed Atom Transfer Radical Addition Reactions and Related Processes. AB - Visible-light photoredox catalysis offers exciting opportunities to achieve challenging carbon-carbon bond formations under mild and ecologically benign conditions. Desired features of photoredox catalysts are photostability, long excited-state lifetimes, strong absorption in the visible region, and high reduction or oxidation potentials to achieve electron transfer to substrates, thus generating radicals that can undergo synthetic organic transformations. These requirements are met in a convincing way by Ru(II)(phenanthroline)3- and Ir(III)(phenylpyridine)3-type complexes and, as a low-cost alternative, by organic dyes that offer a metal-free catalyst but suffer in general from lower photostability. Cu(I)(phenanthroline)2 complexes have been recognized for more than 30 years as photoresponsive compounds with highly negative Cu(I)* -> Cu(II) oxidation potentials, but nevertheless, they have not been widely considered as suitable photoredox catalysts, mainly because their excited lifetimes are shorter by a factor of 5 to 10 compared with Ru(II) and Ir(III) complexes, their absorption in the visible region is weak, and their low Cu(II) -> Cu(I) reduction potentials might impede the closure of a catalytic cycle for a given process. Contrasting again with Ru(II)L3 and Ir(III)L3 complexes, Cu(I)L2 assemblies undergo more rapid ligand exchange in solution, thus potentially reducing the concentration of the photoactive species. Focusing on atom transfer radical addition (ATRA) reactions and related processes, we highlight recent developments that show the utility of Cu(I)(phenanthroline)2 complexes as photoredox catalysts, demonstrating that despite their short excited-state lifetimes and weak absorption such complexes are efficient at low catalyst loadings. Moreover, some of the inherent disadvantages stated above can even be turned to advantages: (1) the low Cu(II) -> Cu(I) reduction potential might efficiently promote reactions via a radical chain pathway, and (2) the tendency for ligand exchange in Cu(I)L2 assemblies allows the efficient synthesis of heteroleptic Cu(I)LL' complexes to tune the steric and electronic properties and also might coordinate and thus activate substrates in the course of a reaction in addition to electron transfer. Moreover, new photoredox cycles have also been discovered beyond the visible-light-induced Cu(I)* -> Cu(II) electron transfer that is arguably best known: examples of the Cu(II)* -> Cu(I) and Cu(I)* -> Cu(0) transitions have been realized, greatly broadening the potential for copper-based photoredox-catalyzed transformations. Finally, a number of organic transformations that are unique to Cu(I) photoredox catalysts have been discovered. PMID- 27556933 TI - Stereotactic ablative radiotherapy and immunotherapy combinations: turning the future into systemic therapy? AB - Radiotherapy (RT) is effective at cytoreducing tumours and until relatively recently the focus in radiobiology has been on the direct effects of RT on the tumour. Increasingly, however, the effect of RT on the tumour vasculature, tumour stroma and immune system are recognized as important to the overall outcome. RT is known to lead to the induction of immunogenic cell death (ICD), which can generate tumour-specific immunity. However, systemic immunity leading to "abscopal effects" resulting in tumour shrinkage outside of the RT treatment field is rare, which is thought to be caused by the immunosuppressive nature of the tumour microenvironment. Recent advances in understanding the nature of this immunosuppression and therapeutics targeting immune checkpoints such as programmed death 1 has led to durable clinical responses in a range of cancer types including malignant melanoma and non-small-cell lung cancer. The effects of RT dose and fraction on the generation of ICD and systemic immunity are largely unknown and are currently under investigation. Stereotactic ablative radiotherapy (SABR) provides an opportunity to deliver single or hypofractionated large doses of RT and potentially increase the amount of ICD and the generation of systemic immunity. Here, we review the interplay of RT and the tumour microenvironment and the rationale for combining SABR with immunomodulatory agents to generate systemic immunity and improve outcomes. PMID- 27556934 TI - Dynamic Response in Nanoelectrowetting on a Dielectric. AB - Droplet spreading at an applied voltage underlies the function of tunable optical devices including adjustable lenses and matrix display elements. Faster response and the enhanced resolution motivate research toward miniaturization of these devices to nanoscale dimensions. The response of an aqueous nanodroplet to an applied field can differ significantly from macroscopic predictions. Understanding these differences requires characterization at the molecular level. We describe the equilibrium and nonequilibrium molecular dynamics simulations of nanosized aqueous droplets on a hydrophobic surface with the embedded concentric electrodes. Constant electrode potential is enforced by a rigorous account of the metal polarization. We demonstrate that the reduction of the equilibrium contact angle is commensurate to, and adjusts reversibly with, the voltage change. For a droplet with O(10) nm diameter, a typical response time to the imposition of the field is of O(10(2)) ps. Drop relaxation is about twice as fast when the field is switched off. The friction coefficient obtained from the rate of the drop relaxation on the nonuniform surface, decreases when the droplet approaches equilibrium from either direction, that is, by spreading or receding. The strong dependence of the friction on the surface hydrophilicity points to the dominance of the liquid-surface friction at the drop's perimeter as described in the molecular kinetic theory. This approach enables correct predictions of trends in dynamic responses associated with varied voltage or substrate material. PMID- 27556935 TI - Pulse Pressure Is Associated With Early Brain Atrophy and Cognitive Decline: Modifying Effects of APOE-epsilon4. AB - We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein E epsilon4 (APOE-epsilon4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-epsilon4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-epsilon4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-epsilon4 carriers. PMID- 27556936 TI - Predicting the Rate of Cognitive Decline in Alzheimer Disease: Data From the ICTUS Study. AB - BACKGROUND: Different rates of cognitive progression have been observed among Alzheimer disease (AD) patients. The present study aimed at evaluating whether the rate of cognitive worsening in AD may be predicted by widely available and easy-to-assess factors. METHODS: Mild to moderate AD patients were recruited in the ICTUS study. Multinomial logistic regression analysis was performed to measure the association between several sociodemographic and clinical variables and 3 different rates of cognitive decline defined by modifications (after 1 year of follow-up) of the Mini Mental State Examination (MMSE) score: (1) "slow" progression, as indicated by a decrease in the MMSE score <=1 point; (2) "intermediate" progression, decrease in the MMSE score between 2 and 5 points; and (3) "rapid" progression, decrease in the MMSE score >=6 points. RESULTS: A total of 1005 patients were considered for the present analyses. Overall, most of the study participants (52%) exhibited a slow cognitive course. Higher ADAS-Cog scores at baseline were significantly associated with both "intermediate" and "rapid" decline. Conversely, increasing age was negatively associated with "rapid" cognitive worsening. CONCLUSIONS: A slow progression of cognitive decline is common among AD patients. The influence of age and baseline cognitive impairment should always be carefully considered when designing AD trials and defining study populations. PMID- 27556937 TI - Pathogenesis, Diagnosis, and Treatment of Venous Thromboembolism in Older Adults. AB - Older adults have a significantly greater risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, than younger adults. The cause of this greater risk is thought to be multifactorial, including age-related changes in hemostatic factors and greater comorbid conditions and hospitalizations, but is not completely understood. Moreover, VTE remains underrecognized in older adults and may present atypically. Thus, a low index of clinical suspicion is essential when evaluating older adults with possible VTE. Despite this underrecognition in older adults, the diagnostic approach remains similar for all age groups and includes estimation of pretest probability, measurement of the D-dimer, and imaging. Antithrombotic agents are the mainstay of VTE treatment and, when used appropriately, substantially reduce VTE recurrence and complications. The approval of novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, provide clinicians with new therapeutic options. In some individuals, NOACs may offer advantages over warfarin, including fewer drug interactions, more-predictable anticoagulation, and lower risk of bleeding. Nevertheless, anticoagulation of VTE in older adults should always be performed cautiously, because age is a risk factor for bleeding complications. Identifying modifiable bleeding risk factors and balancing the risks of VTE recurrence with hemorrhage are important considerations when using anticoagulants in older adults. PMID- 27556939 TI - Corrigendum: Lytic to temperate switching of viral communities. PMID- 27556938 TI - Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. AB - Serotonin (also known as 5-hydroxytryptamine (5-HT)) is a neurotransmitter that has an essential role in the regulation of emotion. However, the precise circuits have not yet been defined through which aversive states are orchestrated by 5-HT. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (CRFBNST) in mice. Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5 HT2CRs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area and lateral hypothalamus. Furthermore, we demonstrate that this CRFBNST inhibitory circuit underlies aversive behaviour following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin-releasing factor type 1 receptor (CRF1R, also known as CRHR1), given that CRF1R antagonism is sufficient to prevent acute SSRI-induced enhancements in aversive learning. These results reveal an essential 5-HTDRN->CRFBNST circuit governing fear and anxiety, and provide a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders. PMID- 27556941 TI - Ageing: Dietary protection for genes. PMID- 27556940 TI - A developmental coordinate of pluripotency among mice, monkeys and humans. AB - The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre- and post-implantation EPI development in cynomolgus monkeys (Macaca fascicularis). We show that after specification in the blastocysts, EPI from cynomolgus monkeys (cyEPI) undergoes major transcriptome changes on implantation. Thereafter, while generating gastrulating cells, cyEPI stably maintains its transcriptome over a week, retains a unique set of pluripotency genes and acquires properties for 'neuron differentiation'. Human and monkey pluripotent stem cells show the highest similarity to post-implantation late cyEPI, which, despite co-existing with gastrulating cells, bears characteristics of pre gastrulating mouse EPI and epiblast-like cells in vitro. These findings not only reveal the divergence and coherence of EPI development, but also identify a developmental coordinate of the spectrum of pluripotency among key species, providing a basis for better regulation of human pluripotency in vitro. PMID- 27556942 TI - Immunology: Cytotoxic T cells that escape exhaustion. PMID- 27556943 TI - Surface patterning of nanoparticles with polymer patches. AB - Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest. Surface patterned particles act as colloidal analogues of atoms and molecules, serve as model systems in studies of phase transitions in liquid systems, behave as 'colloidal surfactants' and function as templates for the synthesis of hybrid particles. The generation of micrometre- and submicrometre-sized patchy colloids is now efficient, but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size- and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties. At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles, and nanoparticles with surface ripples or a 'raspberry' surface morphology. Here we demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. These patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization. PMID- 27556944 TI - Corrigendum: Holocene shifts in the assembly of plant and animal communities implicate human impacts. PMID- 27556945 TI - An endosomal tether undergoes an entropic collapse to bring vesicles together. AB - An early step in intracellular transport is the selective recognition of a vesicle by its appropriate target membrane, a process regulated by Rab GTPases via the recruitment of tethering effectors. Membrane tethering confers higher selectivity and efficiency to membrane fusion than the pairing of SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) alone. Here we address the mechanism whereby a tethered vesicle comes closer towards its target membrane for fusion by reconstituting an endosomal asymmetric tethering machinery consisting of the dimeric coiled-coil protein EEA1 (refs 6, 7) recruited to phosphatidylinositol 3-phosphate membranes and binding vesicles harbouring Rab5. Surprisingly, structural analysis reveals that Rab5:GTP induces an allosteric conformational change in EEA1, from extended to flexible and collapsed. Through dynamic analysis by optical tweezers, we confirm that EEA1 captures a vesicle at a distance corresponding to its extended conformation, and directly measure its flexibility and the forces induced during the tethering reaction. Expression of engineered EEA1 variants defective in the conformational change induce prominent clusters of tethered vesicles in vivo. Our results suggest a new mechanism in which Rab5 induces a change in flexibility of EEA1, generating an entropic collapse force that pulls the captured vesicle towards the target membrane to initiate docking and fusion. PMID- 27556946 TI - Restricted diet delays accelerated ageing and genomic stress in DNA-repair deficient mice. AB - Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1?/-) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair deficient, progeroid Xpg-/- (also known as Ercc5-/-) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1?/- mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1?/- mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of gammaH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1?/- mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general. PMID- 27556947 TI - Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs. AB - Ca2+ antagonist drugs are widely used in therapy of cardiovascular disorders. Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on CaV1.2 channels, the most prominent voltage-gated Ca2+ (CaV) channel type in myocytes in cardiac and vascular smooth muscle. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca2+ channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore. The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model CaV channel CaVAb, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca2+ interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on CaV channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases. PMID- 27556948 TI - Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling. AB - Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes. Kinase suppressor of Ras (KSR) is a MAPK scaffold that is subject to allosteric regulation through dimerization with RAF. Direct targeting of KSR could have important therapeutic implications for cancer; however, testing this hypothesis has been difficult owing to a lack of small-molecule antagonists of KSR function. Guided by KSR mutations that selectively suppress oncogenic, but not wild-type, Ras signalling, we developed a class of compounds that stabilize a previously unrecognized inactive state of KSR. These compounds, exemplified by APS-2-79, modulate KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK (mitogen-activated protein kinase kinase). Furthermore, APS-2-79 increased the potency of several MEK inhibitors specifically within Ras-mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. These results reveal conformational switching in KSR as a druggable regulator of oncogenic Ras, and further suggest co-targeting of enzymatic and scaffolding activities within Ras-MAPK signalling complexes as a therapeutic strategy for overcoming Ras-driven cancers. PMID- 27556949 TI - Nodal-chain metals. AB - The band theory of solids is arguably the most successful theory of condensed matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain-a chain of connected loops in momentum space-along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF4), as well as in other compounds of this class of materials. Using IrF4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations. PMID- 27556950 TI - HER2 expression identifies dynamic functional states within circulating breast cancer cells. AB - Circulating tumour cells in women with advanced oestrogen-receptor (ER) positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER+/HER2- primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2+ and HER2- subpopulations: HER2+ circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2- circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2+ and HER2- circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2+ and HER2- circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2- phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance. PMID- 27556951 TI - Addition of multiple limiting resources reduces grassland diversity. AB - Niche dimensionality provides a general theoretical explanation for biodiversity more niches, defined by more limiting factors, allow for more ways that species can coexist. Because plant species compete for the same set of limiting resources, theory predicts that addition of a limiting resource eliminates potential trade-offs, reducing the number of species that can coexist. Multiple nutrient limitation of plant production is common and therefore fertilization may reduce diversity by reducing the number or dimensionality of belowground limiting factors. At the same time, nutrient addition, by increasing biomass, should ultimately shift competition from belowground nutrients towards a one-dimensional competitive trade-off for light. Here we show that plant species diversity decreased when a greater number of limiting nutrients were added across 45 grassland sites from a multi-continent experimental network. The number of added nutrients predicted diversity loss, even after controlling for effects of plant biomass, and even where biomass production was not nutrient-limited. We found that elevated resource supply reduced niche dimensionality and diversity and increased both productivity and compositional turnover. Our results point to the importance of understanding dimensionality in ecological systems that are undergoing diversity loss in response to multiple global change factors. PMID- 27556953 TI - Heptaketides from an Endolichenic Fungus Biatriospora sp. and Their Antifungal Activity. AB - Twelve new heptaketides, biatriosporins A-L (1-12), biatriosporin M (13) (a ramulosin derivative), and 19 known compounds (14-32) were isolated from the endolichenic fungus Biatriospora sp. (8331C). The structures of these compounds were determined by analyzing MS and NMR data. The absolute configurations of compounds 1, 2, 7, and 9 were determined by single-crystal X-ray diffraction analysis, whereas compound 10 was deduced with Mosher's method. Four of the compounds were active in an antifungal assay. The most potent compound, compound 4, also sensitized clinically derived azole-resistant Candida albicans strains to fluconazole (FLC). A mechanistic investigation revealed that 4 inhibited the function of efflux pumps and reduced the transcriptional expression of the efflux pump-related genes CDR1 and CDR2. PMID- 27556954 TI - Universal Screening for Mismatch-Repair Deficiency in Endometrial Cancers to Identify Patients With Lynch Syndrome and Lynch-like Syndrome. AB - Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n=242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate. When consent was obtained, tumor samples underwent next-generation sequencing. A total of 11 unmethylated MMR-deficient cases (4.5% of cohort) were identified through IHC screening. Germline testing was performed in 10 cases and confirmed LS in 4 patients (1.7% of cohort). Of our 4 confirmed LS cases, 1 did not meet traditional LS screening criteria (eg, age below 50 y, Revised Bethesda criteria). In addition, universal screening identified 6 germline-negative MMR-deficient nonmethylated cases, 4 of which occurred in women older than 50. Although our next-generation sequencing data suggest somatic mutations in 4 of these cases, it is possible that these cases may represent cases of "Lynch-like syndrome." We conclude that a subset of LS cases could be missed using traditional screening guidelines. The value of screening for Lynch-like syndrome has yet to be determined. Although the cost effectiveness of universal screening in EC has yet to be elucidated, we conclude that universal IHC screening is currently a reasonable, and arguably superior, approach to screening for LS. PMID- 27556952 TI - Biosynthesis, remodeling and turnover of mitochondrial cardiolipin. AB - Among mitochondrial lipids, cardiolipin occupies a unique place. It is the only phospholipid that is specific to mitochondria and although it is merely a minor component, accounting for 10-20% of the total phospholipid content, cardiolipin plays an important role in the molecular organization, and thus the function of the cristae. This review covers the formation of cardiolipin, a phospholipid dimer containing two phosphatidyl residues, and its assembly into mitochondrial membranes. While a large body of literature exists on this topic, the review focuses on papers that appeared in the past three years. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum. PMID- 27556955 TI - Comparison of biological properties of 99mTc-labeled cyclic RGD Peptide trimer and dimer useful as SPECT radiotracers for tumor imaging. AB - INTRODUCTION: This study sought to evaluate a 99mTc-labeled trimeric cyclic RGD peptide (99mTc-4P-RGD3) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99mTc-3P-RGD2 in the same animal model. METHODS: HYNIC-4P-RGD3 was prepared by reacting 4P-RGD3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99mTc-4P-RGD3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99mTc-3P-RGD2 (a alphavbeta3-targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the alphavbeta3 specificity of 99mTc-4P-RGD3. RESULTS: 99mTc-4P-RGD3 was prepared with >95% RCP and high specific activity (~200GBq/MUmol). 99mTc-4P-RGD3 and 99mTc-3P-RGD2 shared almost identical tumor uptake and similar biodistribution properties. 99mTc-4P-RGD3 had higher uptake than 99mTc-3P-RGD2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99mTc-4P-RGD3 and 99mTc-3P-RGD2. CONCLUSION: Increasing peptide multiplicity from 3P-RGD2 to 4P-RGD3 offers no advantages with respect to the tumor-targeting capability. 99mTc-4P-RGD3 is as good a SPECT radiotracer as 99mTc-3P-RGD2 for imaging alphavbeta3-positive tumors. PMID- 27556957 TI - The impact of sentinel node dissection on disease-free and overall tumour specific survival in melanoma patients: a single centre group-matched analysis of 1192 patients. AB - BACKGROUND: Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence, removal of potential lymph node micrometastasis will alter survival outcome. OBJECTIVE: The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus SLND group to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma. METHODS AND MATERIALS: A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumour thickness and localization of primary tumour. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in; and hence, subject to change over time. RESULTS: Kaplan-Meier testing revealed significant differences in survival in favour of the SLND group. Mean overall tumour-specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group respectively (P-value: 0.024). Disease-free survival (log-rank test: 0.003) and time to lymph node progression (P-value: <0.01) also differed significantly between the two groups. CONCLUSION: SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumour-specific survival of melanoma patients. PMID- 27556956 TI - RTP801 Amplifies Nicotinamide Adenine Dinucleotide Phosphate Oxidase-4-Dependent Oxidative Stress Induced by Cigarette Smoke. AB - Tobacco smoke (TS) causes chronic obstructive pulmonary disease, including chronic bronchitis, emphysema, and asthma. Rtp801, an inhibitor of mechanistic target of rapamycin, is induced by oxidative stress triggered by TS. Its up regulation drives lung susceptibility to TS injury by enhancing inflammation and alveolar destruction. We postulated that Rtp801 is not only increased by reactive oxygen species (ROS) in TS but also instrumental in creating a feedforward process leading to amplification of endogenous ROS generation. We used cigarette smoke extract (CSE) to model the effect of TS in wild-type (Wt) and knockout (KO Rtp801) mouse lung fibroblasts (MLF). The production of superoxide anion in KO Rtp801 MLF was lower than that in Rtp801 Wt cells after CSE treatment, and it was inhibited in Wt MLF by silencing nicotinamide adenine dinucleotide phosphate oxidase-4 (Nox4) expression with small interfering Nox4 RNA. We observed a cytoplasmic location of ROS formation by real-time redox changes using reduction oxidation-sensitive green fluorescent protein profluorescent probes. Both the superoxide production and the increase in the cytoplasmic redox were inhibited by apocynin. Reduction in the activity of Sod and decreases in the expression of Sod2 and Gpx1 genes were associated with Rtp801 CSE induction. The ROS produced by Nox4 in conjunction with the decrease in cellular antioxidant enzymatic defenses may account for the observed cytoplasmic redox changes and cellular damage caused by TS. PMID- 27556958 TI - Tactile Ranschburg effects: facilitation and inhibitory repetition effects analogous to verbal memory. AB - The present paper examines the effect of within-sequence item repetitions in tactile order memory. Employing an immediate serial recall procedure, participants reconstructed a six-item sequence tapped upon their fingers by moving those fingers in the order of original stimulation. In Experiment 1a, within-sequence repetition of an item separated by two-intervening items resulted in a significant reduction in recall accuracy for that repeated item (i.e., the Ranschburg effect). In Experiment 1b, within-sequence repetition of an adjacent item resulted in significant recall facilitation for that repeated item. These effects mirror those reported for verbal stimuli (e.g., Henson, 1998a . Item repetition in short-term memory: Ranschburg repeated. Journal of Experimental Psychology: Learning, Memory, and Cognition, 24(5), 1162-1181. doi:doi.org/10.1037/0278-7393.24.5.1162). These data are the first to demonstrate the Ranschburg effect with non-verbal stimuli and suggest further cross-modal similarities in order memory. PMID- 27556959 TI - Venous Sinus Stenting in Idiopathic Intracranial Hypertension: Results of a Prospective Trial. AB - BACKGROUND: Our goal was to evaluate the safety and efficacy of stenting of venous sinus stenosis (VSS) in patients with medically-refractory, medically intolerant or fulminant idiopathic intracranial hypertension (IIH) in a prospective, observational study. METHODS: Thirteen patients with IIH who were refractory or intolerant to medical therapy or who presented with fulminant visual field (VF) loss underwent stenting of VSS at the transverse-sinus sigmoid sinus junction, using a Precise Pro carotid stent system (Cordis). Inclusion criteria included papilledema-related VF loss with mean deviation (MD) worse than or equal to -6.00 dB, elevated opening pressure (OP) on lumbar puncture (LP), VSS (either bilateral or unilateral in a dominant sinus), and an elevated (>=8 mm Hg) trans-stenotic gradient (TSG). The main outcome measures were pre- to post-stent change in symptoms related to intracranial hypertension, MD (in dB) on automated (Humphrey) VFs, grade of papilledema (1-5), retinal nerve fiber layer (RNFL) thickness as measured by spectral domain optical coherence tomography (SD-OCT), TSG (mm Hg), and OP on LP (cm H20). RESULTS: Improvement or resolution of headaches occurred in 84.7% of patients, pulse-synchronous tinnitus in 100%, diplopia in 100%, and transient visual obscuration in 100%. Out of 26 eyes, 21 showed an improvement in MD, with an average improvement of +5.40 dB. Of 24 eyes with initial papilledema, 20 showed an improvement in Frisen grade, (mean change in grade of 1.90). Of 23 eyes undergoing SD-OCT, 21 (91.3%) demonstrated a reduction in RNFL thickness, with a poststent mean thickness of 90.48 MUm. Mean change in OP was -20 cm H2O (reduction in mean from 42 to 22 cm H20) with all subjects demonstrating a reduction, although a second stenting procedure was necessary in one patient. Complications of the stenting procedure included one small, self-limited retroperitoneal hemorrhage, transient head or pelvic pain, and one allergic reaction to contrast. No serious adverse events occurred. CONCLUSIONS: Stenting of VSS is safe and results in reduction of intracranial pressure in patients with IIH. This is associated with improvement in papilledema, RNFL thickness, VF parameters, and symptoms associated with intracranial hypertension. PMID- 27556960 TI - Diagnosing Light Chain Amyloidosis on Temporal Artery Biopsies for Suspected Giant Cell Arteritis. AB - Although still rarely diagnosed, amyloid light chain (AL) amyloidosis is the most common form of systemic amyloidosis. It is characterized by misfolded monoclonal immunoglobulin light chain fragments that accumulate extracellularly as amyloid fibrils, with consequent organ dysfunction. We report 2 such cases where initial symptoms and signs were identical to and mistaken for those of giant cell arteritis, associated with polymyalgia rheumatica. Neither patient responded to high-dose corticosteroids; instead, their temporal artery biopsies revealed amyloid deposits and other investigations confirmed a diagnosis of systemic AL amyloidosis. Review of the literature reveals similar cases of diagnostic confusion spanning 75 years. We have summarized the findings and learning points from cases reported in the past 30 years and highlight the need for increased awareness and investigation of this underrecognized syndrome. PMID- 27556961 TI - Principal components analysis to characterise fatigue-related changes in technique: Application to double under jump rope. AB - The upper extremities play an important role in managing the rope-turning technique required to perform continuous double unders. However, acute adaptions in this technique may occur as a jumper fatigues. The purpose of this study was to examine how turning technique is adapted with fatigue. Three-dimensional kinematic data of the upper extremity were collected from 10 trained athletes as they performed consecutive double unders to volitional fatigue. Time series wrist, elbow and shoulder joint angles were calculated where joint angle waveforms representing 10 unique trials from the beginning ("fresh") and end ("fatigued") of the continuous jumping protocol for all participants were analysed using principal component analysis. Participants reported stopping due to cardiovascular and shoulder muscular fatigue. From a kinematics perspective, with fatigue athletes used a more internally rotated range of motion at the shoulder, which we believe prompted a series of more distal adaptions in order to maintain rope turning, preserving consecutive double under performance. The presence of a maladaptive adaptation at the shoulder may increase the risk of developing shoulder injuries. Coaches should consider helping jumpers develop appropriate shoulder muscle endurance such that they can continue to maximise their training and proficiency, while protecting against potential fatigue related maladaptation. PMID- 27556962 TI - The pharmacokinetics of propofol in ICU patients undergoing long-term sedation. AB - The aim of this study was to characterize the pharmacokinetics (PK) of propofol in ICU patients undergoing long-term sedation and to assess the influence of routinely collected covariates on the PK parameters. Propofol concentration-time profiles were collected from 29 patients. Non-linear mixed-effects modelling in NONMEM 7.2 was used to analyse the observed data. The propofol pharmacokinetics was best described with a three-compartment disposition model. Non-parametric bootstrap and a visual predictive check were used to evaluate the adequacy of the developed model to describe the observations. The typical value of the propofol clearance (1.46 l/min) approximated the hepatic blood flow. The volume of distribution at steady state was high and was equal to 955.1 l, which is consistent with other studies involving propofol in ICU patients. There was no statistically significant covariate relationship between PK parameters and opioid type, SOFA score on the day of admission, APACHE II, predicted death rate, reason for ICU admission (sepsis, trauma or surgery), gender, body weight, age, infusion duration and C-reactive protein concentration. The population PK model was developed successfully to describe the time-course of propofol concentration in ICU patients undergoing prolonged sedation. Despite a very heterogeneous group of patients, consistent PK profiles were observed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27556963 TI - Accuracy of probabilistic and deterministic record linkage: the case of tuberculosis. AB - OBJECTIVE: To analyze the accuracy of deterministic and probabilistic record linkage to identify TB duplicate records, as well as the characteristics of discordant pairs. METHODS: The study analyzed all TB records from 2009 to 2011 in the state of Rio de Janeiro. A deterministic record linkage algorithm was developed using a set of 70 rules, based on the combination of fragments of the key variables with or without modification (Soundex or substring). Each rule was formed by three or more fragments. The probabilistic approach required a cutoff point for the score, above which the links would be automatically classified as belonging to the same individual. The cutoff point was obtained by linkage of the Notifiable Diseases Information System - Tuberculosis database with itself, subsequent manual review and ROC curves and precision-recall. Sensitivity and specificity for accurate analysis were calculated. RESULTS: Accuracy ranged from 87.2% to 95.2% for sensitivity and 99.8% to 99.9% for specificity for probabilistic and deterministic record linkage, respectively. The occurrence of missing values for the key variables and the low percentage of similarity measure for name and date of birth were mainly responsible for the failure to identify records of the same individual with the techniques used. CONCLUSIONS: The two techniques showed a high level of correlation for pair classification. Although deterministic linkage identified more duplicate records than probabilistic linkage, the latter retrieved records not identified by the former. User need and experience should be considered when choosing the best technique to be used. OBJETIVO: Analisar a acuracia das tecnicas deterministica e probabilistica para identificacao de registros duplicados de tuberculose, assim como as caracteristicas dos pares discordantes. METODOS: Foram analisados todos os registros de tuberculose no periodo de 2009 a 2011 do estado do Rio de Janeiro. Foi desenvolvido algoritmo para relacionamento deterministico, usando conjunto de 70 regras, a partir da combinacao de fragmentos das variaveis-chave com ou sem modificacoes (Soundex ou substring). Cada regra era formada por tres ou mais fragmentos. Para a abordagem probabilistica, foi necessario estabelecer ponto de corte para o escore, acima do qual os links seriam classificados automaticamente como pertencentes ao mesmo individuo. O ponto de corte foi obtido por meio do relacionamento da base de dados Sistema de Informacao de Agravos de Notificacao - Tuberculose com ela mesma, posterior revisao manual e curvas ROC e precision recall. Foram calculadas a sensibilidade e especificidade para analise de acuracia. RESULTADOS: A acuracia variou de 87,2% a 95,2% para sensibilidade e 99,8% a 99,9% para especificidade para as tecnicas probabilistica e deterministica, respectivamente. A presenca de valores faltantes para as variaveis-chave e o baixo percentual da medida de similaridade para o nome e data de nascimento foram os principais responsaveis pela nao identificacao dos registros do mesmo individuo pelas tecnicas utilizadas. CONCLUSOES: As duas tecnicas apresentam alta concordancia para a classificacao como par. Apesar de a tecnica deterministica ter identificado mais registros duplicados que a probabilistica, a segunda recuperou registros nao identificados pela primeira. A necessidade e a experiencia do usuario devem ser consideradas para a escolha da tecnica a ser utilizada. PMID- 27556965 TI - Network as transconcept: elements for a conceptual demarcation in the field of public health. AB - The main proposal to set up an articulated mode of operation of health services has been the concept of network, which has been appropriated in different ways in the field of public health, as it is used in other disciplinary fields or even taking it from common sense. Amid the diversity of uses and concepts, we recognize the need for rigorous conceptual demarcation about networks in the field of health. Such concern aims to preserve the strategic potential of this concept in the research and planning in the field, overcoming uncertainties and distortions still observed in its discourse-analytic circulation in public health. To this end, we will introduce the current uses of network in different disciplinary fields, emphasizing dialogues with the field of public health. With this, we intend to stimulate discussions about the development of empirical dimensions and analytical models that may allow us to understand the processes produced within and around health networks. RESUMO A principal proposta para configurar um modo articulado de funcionamento dos servicos de saude tem sido o conceito de rede, que vem sendo apropriado de diferentes formas no campo da saude coletiva, conforme seu emprego em outros campos disciplinares ou mesmo tomando-o do senso comum. Em meio a pluralidade de usos e concepcoes, reconhecemos a necessidade de rigorosa demarcacao conceitual acerca de redes no campo da saude. Tal preocupacao visa a preservar o potencial estrategico desse conceito na investigacao e planificacao no campo, superando precariedades e distorcoes ainda observadas em sua circulacao discursivo-analitica na saude coletiva. Para tanto, apresentaremos os usos correntes de rede em diferentes campos disciplinares, destacando interlocucoes com o campo da saude coletiva. Com isso, pretendemos estimular o debate acerca do desenvolvimento de dimensoes empiricas e modelos de analise que permitam compreender os processos produzidos no interior e ao redor das redes de saude. PMID- 27556964 TI - Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis. AB - OBJECTIVE: To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS: This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients' chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS: The study included 11,642 patients with rheumatoid arthritis - 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD - and 1,251 patients with ankylosing spondylitis - 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS: A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing spondylitis as compared to rheumatoid arthritis; and a higher persistence for DMARD in patients with rheumatoid arthritis as compared to ankylosing spondylitis. OBJETIVO: Avaliar a persistencia do tratamento em pacientes com artrite reumatoide e espondilite anquilosante que iniciaram terapia com medicamentos modificadores do curso da doenca (MMCD) e agentes bloqueadores do fator de necrose tumoral (anti-TNF). METODOS: Este estudo de coorte retrospectiva de julho de 2008 a setembro de 2013 avaliou a persistencia na terapia, definida como o tempo do inicio ate a descontinuacao, permitindo-se um intervalo de ate 30 dias entre o fim da prescricao e o inicio da prescricao seguinte. Odds ratio (OR) com intervalos de confianca de 95% (IC95%) foram calculados por meio de modelos de regressao logistica para estimar a chance de apresentar persistencia na terapia apos o primeiro e os dois primeiros anos de seguimento. RESULTADOS: Foram incluidos 11.642 pacientes com artrite reumatoide - 2.241 iniciaram uso de agentes anti-TNF (+/-MMCD) e 9.401 iniciaram MMCD - e 1.251 pacientes com espondilite anquilosante - 976 iniciaram uso de agentes anti TNF (+/-MMCD) e 275 iniciaram MMCD. No primeiro ano de acompanhamento, 63,5% persistiram em terapia com anti-TNF (+/-MMCD) e 54,1% em uso de MMCD do grupo com artrite reumatoide. Em relacao a espondilite anquilosante, 79,0% do grupo anti TNF (+/-MMCD) e 41,1% do grupo MMCD persistiram no tratamento. O OR (IC95%) para persistencia na terapia foi de 1,50 (1,34-1,67) para o grupo anti-TNF (+/-MMCD) comparado com MMCD no primeiro ano em pacientes com artrite reumatoide, e de 2,33 (1,74-3,11) em pacientes com espondilite anquilosante. Foi observada tendencia semelhante ao final do segundo ano. CONCLUSOES: Observou-se uma tendencia geral de taxas mais elevadas de persistencia na terapia com anti-TNF (+/-MMCD) em relacao a MMCD no periodo estudado. Foram observadas taxas de persistencia mais elevadas para os usuarios de anti-TNF (+/-MMCD) em pacientes com espondilite anquilosante em relacao a artrite reumatoide, e maior persistencia para MMCD em pacientes com artrite reumatoide em relacao a espondilite anquilosante. PMID- 27556966 TI - Cross-cultural adaptation and validation of the teamwork climate scale. AB - OBJECTIVE: To adapt and validate the Team Climate Inventory scale, of teamwork climate measurement, for the Portuguese language, in the context of primary health care in Brazil. METHODS: Methodological study with quantitative approach of cross-cultural adaptation (translation, back-translation, synthesis, expert committee, and pretest) and validation with 497 employees from 72 teams of the Family Health Strategy in the city of Campinas, SP, Southeastern Brazil. We verified reliability by the Cronbach's alpha, construct validity by the confirmatory factor analysis with SmartPLS software, and correlation by the job satisfaction scale. RESULTS: We problematized the overlap of items 9, 11, and 12 of the "participation in the team" factor and the "team goals" factor regarding its definition. The validation showed no overlapping of items and the reliability ranged from 0.92 to 0.93. The confirmatory factor analysis indicated suitability of the proposed model with distribution of the 38 items in the four factors. The correlation between teamwork climate and job satisfaction was significant. CONCLUSIONS: The version of the scale in Brazilian Portuguese was validated and can be used in the context of primary health care in the Country, constituting an adequate tool for the assessment and diagnosis of teamwork. OBJETIVO: Adaptar e validar a escala Team Climate Invetory, de medida do clima de trabalho em equipe, para o idioma portugues, no contexto da atencao primaria a saude no Brasil. METODOS: Estudo metodologico com abordagem quantitativa de adaptacao transcultural (traducao, retrotraducao, sintese, comite de especialistas e pre teste) e validacao com 497 trabalhadores de 72 equipes da Estrategia Saude da Familia no municipio de Campinas, Sao Paulo. Verificou-se confiabilidade pelo alfa de Cronbach, validade de construto pela analise fatorial confirmatoria pelo software SmartPLS e correlacao com escala de satisfacao no trabalho. RESULTADOS: Foi problematizado a sobreposicao dos itens 9, 11 e 12 do fator participacao na equipe e o fator objetivos da equipe no tocante a sua definicao. A validacao mostrou que nao houve sobreposicao dos itens e a confiabilidade variou entre 0,92 a 0,93. A analise fatorial confirmatoria indicou adequacao do modelo proposto com distribuicao dos 38 itens nos quatro fatores. A correlacao entre clima de trabalho em equipe e satisfacao no trabalho foi significativa. CONCLUSOES: A versao da escala em portugues falado no Brasil foi validada e pode ser utilizada no contexto da atencao primaria a saude no Pais, constituindo ferramenta adequada para a avaliacao e diagnostico do trabalho em equipe. PMID- 27556967 TI - Self-perception of oral health in older adults from an urban population in Lisbon, Portugal. AB - OBJECTIVE: To analyze if the self-perception of oral health in the urban context is associated with sociodemographic factors that interfere in the life quality of oral health. METHODS: Cross-sectional study with convenience sample of older individuals (65 years old or more) enrolled in the Agrupamento de Centros de Saude de Lisboa Norte (ACES Lisboa Norte - Health Centers Groupings North Lisbon). The self-perception of oral health and associated life quality was evaluated by the Geriatric Oral Health Assessment Index and the individuals were classified according to sociodemographic characteristics. The internal consistency of the questionnaire was evaluated by Cronbach's alpha (alpha). Later, we used binary logistic regression models to characterize the factors associated with the self-perception of oral health, considering the sociodemographic variables and the older adults' clinical conditions of oral health and establishing the crude and adjusted (to age) odds ratios and their 90% confidence intervals. RESULTS: A total of 369 older adults participated in this study, with an average age of 74.2 years (SD = 6.75); 62.9% were female. On average, the index was moderated, with tendency to be high: 32.9 (SD = 3.6; 12-36 interval). The Cronbach's alpha was high: 0.805. Age, marital status, and the last dental appointment were the factors significantly associated with self perception of oral health. CONCLUSIONS: The study shows that these individuals have a moderate, with tendency to high, self-perception of oral health. The self perception of oral health assessment allowed us to identify the main associated sociodemographic factors. This instrument can help guiding planning strategies and oral health promotion directed toward a better life quality for this population group. OBJETIVO: Analisar se a autopercepcao de saude bucal em contexto urbano esta associada aos factores sociodemograficos que interferem na qualidade de vida da saude bucal. METODOS: Estudo transversal com amostra de conveniencia de individuos idosos (65 anos ou mais) inscritos no Agrupamento de Centros de Saude de Lisboa Norte. A autopercepcao da saude bucal e qualidade de vida associada foi avaliada pelo indice de avaliacao da saude bucal em idosos (Geriatric Oral Health Assessment Index) e os individuos foram classificados de acordo com as caracteristicas sociodemograficas. A consistencia interna do questionario foi avaliada por meio do alfa (alpha) de Cronbach. Posteriormente, foram utilizados modelos de regressao logistica binaria para caracterizar os factores associados com a autopercepcao de saude bucal considerando as variaveis sociodemograficas e de condicoes clinicas de saude bucal dos idosos e determinados os odds ratios bruto e ajustado (a idade) e respectivos intervalos de confianca a 90%. RESULTADOS: Participaram 369 idosos, com media de idade de 74,2 anos (DP = 6,75); 62,9% eram do sexo feminino. Em media, o indice foi moderado com tendencia a elevado: 32,9 (DP = 3,6; intervalo 12-36). O alfa de Cronbach foi elevado: 0,805. A idade, o estado civil e a ultima consulta de Medicina Dentaria foram os factores significativamente associados a autopercepcao da saude bucal. CONCLUSOES: O estudo mostra que esses individuos apresentam uma autopercepcao de saude bucal moderada, com tendencia a elevada. A avaliacao da autopercepcao da saude bucal permitiu identificar os principais factores sociodemograficos associados. Este instrumento pode contribuir para orientar as estrategias de planejamento e promocao da saude bucal direcionadas para uma melhor qualidade de vida deste grupo populacional. PMID- 27556969 TI - Cavity-dumped Yb:YAG ceramic in the 20 W, 12 mJ range at 6.7 ns operating from 20 Hz to 5 kHz with fluorescence feedback control. AB - Increasing data acquisition rates in metrology applications based on optical parametric oscillators (OPOs) can accelerate measurement processes. To achieve this, flash-lamp systems with low pulse repetition frequencies of 10-100 Hz used as a pump source for the OPOs could be replaced by diode-pumped solid-state lasers in the kHz range. We demonstrate a 969 nm pumped Yb:YAG ceramic laser yielding 21.6 W output power, 12.5 mJ pulse energy, and excellent beam quality. Fluorescence feedback control, developed from gain dynamics simulations in two operating regimes, allows stable operation at 6.7 ns from 20 to 5000 Hz. Third harmonic generation to 343 nm yields 3.24 W at 2 kHz. The system provides constant pulse duration in a huge repetition rate interval, which is beneficial for pump sources for future metrology devices. PMID- 27556968 TI - Late presentation to HIV/AIDS care in Brazil among men who self-identify as heterosexual. AB - OBJECTIVE: To analyze the factors associated with late presentation to HIV/AIDS services among heterosexual men. METHODS: Men infected by HIV who self-identified as heterosexual (n = 543) were included in the study. Descriptive, biivariate and logistic regression analyses were performed to evaluate the factors associated with late presentation (defined as individuals whose first CD4 count was <350 cells/mm3) in the study population. RESULTS: The prevalence of late presentation was 69.8%. The multivariate logistic analysis showed testing initiated by the provider (ORadjusted 3.75; 95%CI 2.45-5.63) increased the odds of late presentation. History of drug use (ORadjusted 0.59; 95%CI 0.38-0.91), history of having sexually transmitted infections (ORadjusted 0.64; 95%CI 0.42-0.97), and having less education (ORadjusted 0.63; 95%CI 0.41-0.97) were associated with a decreased odds of LP. CONCLUSIONS: Provider initiated testing was the only variable to increase the odds of late presentation. Since the patients in this sample all self-identified as heterosexual, it appears that providers are not requesting they be tested for HIV until the patients are already presenting symptoms of AIDS. The high prevalence of late presentation provides additional evidence to shift towards routine testing and linkage to care, rather than risk based strategies that may not effectively or efficiently engage individuals infected with HIV. PMID- 27556970 TI - Surface deformation and friction characteristic of nano scratch at ductile removal regime for optical glass BK7. AB - Nano scratch for optical glass BK7 based on the ductile-removal regime was carried out, and the influence rule of scratch parameters on surface deformation and friction characteristic was analyzed. Experimental results showed that, with increase of normal force, the deformation of burrs in the edge of the scratch was more obvious, and with increase of the scratch velocity, the deformation of micro fracture and burrs in the edge of the scratch was more obvious similarly. The residual depth of the scratch was measured by atomic force microscope. The experimental results also showed that, with increase of normal force, the residual depth of the scratch increased linearly while the elastic recovery rate decreased. Furthermore, with increase of scratch velocity, the residual depth of the scratch decreased while the elastic recovery rate increased. The scratch process of the Berkovich indenter was divided into the cutting process of many large negative rake faces based on the improved cutting model, and the friction characteristic of the Berkovich indenter and the workpiece was analyzed. The analysis showed that the coefficient of friction increased and then tended to be stable with the increase of normal force. Meanwhile, the coefficient of friction decreased with the increase of scratch velocity, and the coefficients, k ln(v) and MU0, were introduced to improve the original formula of friction coefficient. PMID- 27556971 TI - Compact KGd(WO4)2 picosecond pulse-train synchronously pumped broadband Raman laser. AB - We demonstrate an efficient approach to realizing an extra-cavity, synchronously pumped, stimulated Raman cascaded process under low repetition frequency (1 kHz) pump conditions. We also construct a compact KGd(WO4)2 (KGW) crystal picosecond Raman laser that has been configured as the developed method. A pulse-train green laser pumped the corresponding 70 mm long KGW crystal Raman cavity. The pulse train contains six pulses, about 800 ps separated, for every millisecond; thus, it can realize synchronous pumping between pump pulse and the pumped Raman cavity. The investigated system produced a collinear Raman laser output that includes six laser lines covering the 532 to 800 nm spectra. This is the first report on an all-solid-state, high-average-power picosecond collinear multi-wavelength (more than three laser components) laser to our knowledge. This method has never been reported on before in the synchronously pumped stimulated Raman scattering (SRS) realm. PMID- 27556972 TI - Nonlinear diffusion model for annealed proton-exchanged waveguides in zirconium doped lithium niobate. AB - Photorefractive-damage- (PRD) resistant zirconium-oxide-doped lithium niobate is investigated as a substrate for the realization of annealed proton-exchanged (APE) waveguides. Its advantages are a favorable distribution coefficient, PRD resistance comparable to magnesium-oxide-doped lithium niobate, and a proton diffusion behavior resembling congruent lithium niobate. A 1D model for APE waveguides was developed based on a previous model for congruently melting lithium niobate. Evidence for a nonlinear index dependence on concentration was found. PMID- 27556973 TI - Calibration and 3D reconstruction of underwater objects with non-single-view projection model by structured light stereo imaging. AB - Establishing the projection model of imaging systems is critical in 3D reconstruction of object shapes from multiple 2D views. When deployed underwater, these are enclosed in waterproof housings with transparent glass ports that generate nonlinear refractions of optical rays at interfaces, leading to invalidation of the commonly assumed single-viewpoint (SVP) model. In this paper, we propose a non-SVP ray tracing model for the calibration of a projector-camera system, employed for 3D reconstruction based on the structured light paradigm. The projector utilizes dot patterns, having established that the contrast loss is less severe than for traditional stripe patterns in highly turbid waters. Experimental results are presented to assess the achieved calibrating accuracy. PMID- 27556974 TI - Demonstration of random projections applied to the retrieval problem of geophysical parameters from hyper-spectral infrared observations. AB - The random projections statistical technique has been used to reduce the dimensionality of the radiance data space generated from high spectral resolution infrared observations. The mathematical inversion of the physical radiative transfer equation for geophysical parameters has been solved in this space of reduced dimensionality. The great advantage of using random projections is that they provide an unified treatment of instrument noise and forward model error, which can be comprehensively modeled with a single variance term. The result is a novel retrieval approach, which combines computational efficiency to possibly improved accuracy of the retrieval products. The novel approach has been demonstrated through application to the Infrared Atmospheric Sounding Interferometer. We have found that state-of-the-art spectroscopy and related line mixing treatment for the nu2CO2 absorption band, i.e., the fundamental band for temperature retrieval, show an excellent consistency with satellite observations. PMID- 27556975 TI - Influence of target reflection on three-dimensional range gated reconstruction. AB - The range gated technique is a promising laser ranging method that is widely used in different fields such as surveillance, industry, and military. In a range gated system, a reflected laser pulse returned from the target scene contains key information for range reconstruction, which directly affects the system performance. Therefore, it is necessary to study the characteristics and effects of the target reflection factor. In this paper, theoretical and experimental analyses are performed to investigate the influence of target reflection on three dimensional (3D) range gated reconstruction. Based on laser detection and ranging (LADAR) and bidirectional reflection distribution function (BRDF) theory, a 3D range gated reconstruction model is derived and the effect on range accuracy is analyzed from the perspectives of target surface reflectivity and angle of laser incidence. Our theoretical and experimental study shows that the range accuracy is proportional to the target surface reflectivity, but it decreases when the angle of incidence increases to adhere to the BRDF model. The presented findings establish a comprehensive understanding of target reflection in 3D range gated reconstruction, which is of interest to various applications such as target recognition and object modeling. This paper provides a reference for future improvement to perform accurate range compensation or correction. PMID- 27556976 TI - Rapid measurement of spatial light distribution of a short-arc xenon flash lamp. AB - Small short-arc xenon flash lamps, yielding high energy and ultraviolet radiation without cooling structures, provide ideal analytic-instrument light. Improving instrument designs requires accurately determining spatial optical-flux distribution. Thus, this paper presents rapid scanning of a xenon lamp's central light intensity using a high-sensitivity photodiode to capture short light pulses. Results show two-dimensional optical illumination patterns. In the horizontal mode, the anode and cathode lie in the target plane. In the vertical mode, the two electrodes are centered in a circle. Thus, because the xenon lamp's spatial light flux varies by orientation and main driving voltage, we recommend sampling light horizontally in front of the lamp across small angles. PMID- 27556977 TI - Nonlinear evolution of Airy-like beams generated by modulated waveguide arrays. AB - We numerically study the formation of modulated waveguide generated Airy-like beams and their subsequent evolution in homogeneous medium. The results show that the Airy-like beams could be generated from narrow Gaussian beams propagating in one-dimensional transverse separation modulated unbent, cosine bent, or logarithm bent waveguide arrays, respectively. The waveguide-generated Airy-like beams maintain their characteristics when propagating without nonlinearity or under the self-defocusing nonlinearity in homogeneous medium, while the beams are distorted under the self-focusing nonlinearity. The deformation depends on the waveguide bending and the outgoing angles of the Airy-like beams. Our results provide a new way to generate and manipulate the Airy-like beam. PMID- 27556978 TI - Analytical model for radiative transfer including the effects of a rough material interface. AB - The reflected and transmitted radiance due to a source located above a water surface is computed based on models for radiative transfer in continuous optical media separated by a discontinuous air-water interface with random surface roughness. The air-water interface is described as the superposition of random, unresolved roughness on a deterministic realization of a stochastic wave surface at resolved scales. Under the geometric optics assumption, the bidirectional reflection and transmission functions for the air-water interface are approximated by applying regular perturbation methods to Snell's law and including the effects of a random surface roughness component. Formal analytical solutions to the radiative transfer problem under the small-angle scattering approximation account for the effects of scattering and absorption as light propagates through the atmosphere and water and also capture the diffusive effects due to the interaction of light with the rough material interface that separates the two optical media. Results of the analytical models are validated against Monte Carlo simulations, and the approximation to the bidirectional reflection function is also compared to another well-known analytical model. PMID- 27556979 TI - Starlet transform applied to digital Gabor holographic microscopy. AB - In this paper, we show how the starlet transform can be used to process holograms from a digital Gabor holographic microscope. The starlet transform is an undecimated wavelet transform with the property that when performing reconstruction, we only need to add all scales without the use of a synthesis filter bank. When the starlet transform is applied to a hologram, we divide the hologram into a certain number of scales, process them separately, and propagate each one using a numerical diffraction method. After diffraction propagation, we perform processing on complex amplitudes that correspond to individual scales. With the aforementioned procedure, it is possible to reduce the background and effects of parasitic fringes caused by high coherence of a laser, enhance the contrast, and reduce the effects of the twin image. Experimental results confirming the method are presented. PMID- 27556980 TI - High-precision broadband measurement of refractive index by picosecond real-time interferometry. AB - The refractive index is one of the most important quantities that characterize a material's optical properties. However, it is hard to measure this value over a wide range of wavelengths. Here, we demonstrate a new technique to achieve a spectrally broad refractive index measurement. When a broadband pulse passes through a sample, different wavelengths experience different delays. By comparing the delayed pulse to a reference pulse, the zero path difference position for each wavelength can be obtained and the material's dispersion can be retrieved. Our technique is highly robust and accurate, and can be miniaturized in a straightforward manner. PMID- 27556981 TI - Analysis of multigroup and multichannel filtering properties in a ferroelectric dielectric periodic multilayer. AB - In this work, we propose a filter structure using a one-dimensional ferroelectric dielectric periodic multilayer, air/[(ABA)Ns C]Np(ABA)Ns /air, where Ns and Np are the two numbers of periods. Here, B is a dielectric material of SiO2, C is the same as B with a different thickness, and A is taken to be a ferroelectric material Ba55Sr45TiO3+30%Mg2SiO4, whose dielectric constant is very high (epsilon=439 at 10 GHz). The results show that the transmittance spectra have Ns-channel groups at microwave frequencies and these groups can be classified into two types. The first type has only one channel group with Np narrower channels. The other has Ns-1 groups, each of which has Np+1 broader channels. In this filter structure the group number and channel number of each group can be determined simply by changing Ns and Np. PMID- 27556982 TI - Active compensation of wavefront aberrations by controllable heating of lens with electric film heater matrix. AB - We present a new apparatus for active compensation of wavefront aberrations by controllable heating of a lens using a film heater matrix. The annular electric film heater matrix, comprising 24 individual heaters, is attached to the periphery of a lens. Utilizing the linear superposition, and wavefront change proportional to the heating energy properties induced by heating, a controllable wavefront can be defined by solving a linear function. The two properties of wavefront change of a lens have been confirmed through a specially designed experiment. The feasibility of the compensation method is validated by compensating the wavefront of a plate lens. The results show that the wavefront of the lens changes from 12.52 to 2.95 nm rms after compensation. With a more precise electric controlling board, better results could be achieved. PMID- 27556983 TI - Measurements of refractive indices and thermo-optical coefficients using a white light Michelson interferometer. AB - A dispersive white-light Michelson interferometer was used to determine the wavelength dependence of the refractive index (n) in the visible range from 425 to 775 nm and the thermo-optical coefficient (dn/dT) of fused silica (FS) and borosilicate glass (BK7). For FS, the values obtained for n and dn/dT at 546 nm were 1.46079 and 11.3*10-6 K-1, respectively, while the values for BK7 glass were 1.51825 and 2.2*10-6 K-1, respectively, which is in good agreement with the literature. The accuracy of the methodology used for n was almost 10-6, enabling precise spectroscopic characterization of materials across a wide spectral range. PMID- 27556984 TI - High sensitivity optical waveguide accelerometer based on Fano resonance. AB - An optical waveguide accelerometer based on tunable asymmetrical Fano resonance in a ring-resonator-coupled Mach-Zehnder interferometer (MZI) is proposed and analyzed. A Fano resonance accelerometer has a relatively large workspace of coupling coefficients with high sensitivity, which has potential application in inertial navigation, missile guidance, and attitude control of satellites. Due to the interference between a high-Q resonance pathway and a coherent background pathway, a steep asymmetric line shape is generated, which greatly improves the sensitivity of this accelerometer. The sensitivity of the accelerometer is about 111.75 mW/g. A 393-fold increase in sensitivity is achieved compared with a conventional MZI accelerometer and is approximately equal to the single ring structure. PMID- 27556985 TI - Color digital lensless holographic microscopy: laser versus LED illumination. AB - A comparison of the performance of color digital lensless holographic microscopy (CDLHM) as utilized for illumination of RGB lasers or a super-bright white-light LED with a set of spectral filters is presented. As the use of lasers in CDLHM conceals the possibility of having a compact, lightweight, portable, and low cost microscope, and additionally the limited available laser radiation wavelengths limit a real multispectral imaging microscope, here we present the use of super bright white-light LED and spectral filters for illuminating the sample. The performance of RGB laser-CDLHM and LED-CDLHM is evaluated on imaging a section of the head of a Drosophila melanogaster fly. This comparison shows that there is trade-off between the spatial resolution of the microscope and the light sources utilized, which can be understood with regard to the coherence properties of the illuminating light. Despite the smaller spatial coherence features of LED-CDLHM in comparison with laser-CDLHM, the former shows promise as a portable RGB digital lensless holographic microscope that could be extended to other wavelengths by the use of different spectral filters. PMID- 27556986 TI - Study of a micro-concentrated photovoltaic system based on Cu(In,Ga)Se2 microcells array. AB - We study a micro-concentrated photovoltaic (CPV) system based on micro solar cells made from a thin film technology, Cu(In,Ga)Se2. We designed, using the ray-tracing software Zemax OpticStudio 14, an optical system adapted and integrated to the microcells, with only spherical lenses. The designed architecture has a magnification factor of 100* for an optical efficiency of 85% and an acceptance angle of +/-3.5 degrees , without anti-reflective coating. An experimental study is realized to fabricate the first generation prototype on a 5 cm*5 cm substrate. A mini-module achieved a concentration ratio of 72* under AM1.5G, and an absolute efficiency gain of 1.8% for a final aperture area efficiency of 12.6%. PMID- 27556987 TI - GADICON spectrometer for ionosphere far-ultraviolet observation: prototype design, manufacturing, and testing. AB - The design, manufacturing, and testing of an imaging spectrometer prototype that will address new scientific requirements by the observation of the lower atmosphere's impact on the ionosphere are presented. The two sided lateral limb observation covering 130-180 nm far-ultraviolet (FUV) region allows the instrument to perform particle measurements in the daytime and nighttime. In this paper, we focus upon the working design principle, observation, and calibration. PMID- 27556988 TI - Optical performance simulation of free-form optics for an eye implant based on a measurement data enhanced model. AB - This paper describes the application of a modeling approach for precise optical performance prediction of free-form optics-based subsystems on a demonstration model of an eye implant. The simulation model is enhanced by surface data measured on the free-form lens parts. The manufacturing of the free-form lens parts is realized by two different manufacturing processes: ultraprecision diamond machining and microinjection molding. Evaluation of both processes is conducted by a simulation of the optical performance on the basis of their surface measurement comparisons with the nominal geometry. The simulation results indicate that improvements from the process optimization of microinjection molding were obtained for the best manufacturing accuracy. PMID- 27556989 TI - Dynamic analysis of optical microfiber coil resonators. AB - We present transient time analysis of a two-turn optical microfiber coil resonator (MCR). Our dynamic model is based on two sets of equations, coupled mode and nonlinear Schrodinger equations. The pulse response of this device is obtained by numerically solving the modified sets of equations in a dynamic regime. The results show that if the input pulse of the MCR is set at an off resonance wavelength, this resonator operates as an all-pass filter with neither loss nor time delay. But in the case of resonance, the output pulse may have loss and a relatively long time delay, according to the continuous rotation of light between the first and the second turns of the MCR. Tunable time delays up to td=320 ps are obtained by choosing different values of the coupling coefficients. Furthermore, the material and structural dispersions of the MCR are studied, and it is shown that strong dispersive effects can occur even in this millimeter dimensions photonic device. Pulse broadening and distortion effects of the MCR are studied in the dynamic regime. The results show that, for high bit rate applications, the dispersion effects of the MCR should be carefully considered. Finally, fundamental soliton solution and its conditions in the MCR are investigated. PMID- 27556990 TI - Spatially resolved photodiode response for simulating precise interferometers. AB - Quadrant photodiodes (QPDs) are used in laser interferometry systems to simultaneously detect longitudinal displacement of test masses and angular misalignment between the two interfering beams. The latter is achieved by means of the differential wavefront sensing (DWS) technique, which provides ultra-high precision for measuring angular displacements. We have developed a setup to obtain the spatially resolved response of QPDs that, together with an extension of the simulation software IfoCAD, allows us to use the measured response in simulations and accurately predict the desired longitudinal and DWS phase observables. Three different commercial off-the-shelf QPD candidates for space based interferometry were characterized. The measured response of one QPD was used in optical simulations. Nonuniformities in the response of the device and crosstalk between segments do not introduce significant variations in the longitudinal and DWS measurands with respect to the standard case when a uniform QPD without crosstalk is used. PMID- 27556991 TI - Field experiment and image reconstruction using a Fourier telescopy imaging system over a 600-m-long horizontal path. AB - To confirm the effect of uplink atmospheric turbulence on Fourier telescopy (FT), we designed a system for far-field imaging, utilizing a T-type laser transmitting configuration with commercially available hardware, except for a green imaging laser. The horizontal light transmission distance for both uplink and downlink was ~300 m. For both the transmitting and received beams, the height upon the ground was below 1 m. The imaging laser's pointing accuracy was ~9.3 MUrad. A novel image reconstruction approach was proposed, yielding significantly improved quality and Strehl ratio of reconstructed images. From the reconstruction result, we observed that the tip/tilt aberration is tolerated by the FT system even for Changchun's atmospheric coherence length parameter (r0) below 3 cm. The resolution of the reconstructed images was ~0.615 MUrad. PMID- 27556992 TI - Emission enhancement of laser-induced breakdown spectroscopy for aqueous sample analysis based on Au nanoparticles and solid-phase substrate. AB - In this paper, porous electrospun ultrafine fiber with a nanoparticle coating was proposed as an effective approach to enhance the laser-induced breakdown spectroscopy (LIBS) signal for metal ions in aqueous systems. It is known that the LIBS technique is very limited when used for liquid sample analysis. On the other hand, in practical applications, many LIBS measurements have been accomplished in a liquid environment. A signal enhancement method for aqueous sample LIBS analysis was presented in this work, where Au nanoparticles and a solid-phase support were combined for the first time for aqueous sample analysis with LIBS. The system operation was relatively simple, which only required Au nanoparticles being dropped onto the surface of porous electrospun ultrafine fibers before LIBS analysis. Significant signal enhancement was achieved due to the integration of the merits of the Au nanoparticles and the ultrafine fibers. Nanoparticles possess significant LIBS signal enhancement effects by providing several plasma ignition points and then causing more efficient emissions. In addition, Au nanoparticles could also help to decrease the breakdown threshold of target elements for LIBS analysis. The electrospun ultrafine fibers as solid phase support can accommodate a larger volume of aqueous sample. Meanwhile, the aqueous solution on the fiber surface was easy to evaporate. The experimental results showed that the limits of detection (LODs) with this method were significantly improved, 0.5 MUg/mL for Cr, 0.5 MUg/mL for Pb, and 1.1 MUg/mL for Cu, respectively, compared with 2.0 MUg/mL for Cr and 3.3 MUg/mL for Cu in the previous research. In the proposed method, signal enhancement could be achieved without any extra equipment, which makes the LIBS technique feasible for direct measurement of an aqueous sample. PMID- 27556993 TI - Three-frame self-calibration phase shift algorithm using the Gram-Schmidt orthonormalization approach. AB - Affected by the height dependent effects, the phase-shifting shadow moire can only be implemented in an approximate way. In the technique, a fixed phase step around pi/2 rad between two adjacent frames is usually introduced by a grating translation in its own plane. So the method is not flexible in some situations. Additionally, because the shadow moire fringes have a complex intensity distribution, computing the introduced phase shift from the existing arccosine function or arcsine function-based phase shift extraction algorithm always exhibits instability. To solve it, we developed a Gram-Schmidt orthonormalization approach based on a three-frame self-calibration phase-shifting algorithm with equal but unknown phase steps. The proposed method using the arctangent function is fast and can be implemented robustly in many applications. We also do optical experiments to demonstrate the correction of the proposed method by referring to the result of the conventional five-step phase-shifting shadow moire. The results show the correctness of the proposed method. PMID- 27556994 TI - Optical scattering modeling of etched ZnO:Al superstrates and device simulation studies of a-Si:H solar cells with different texture morphologies. AB - Transparent conductive oxide (TCO) materials have been widely used as the front electrodes of thin-film amorphous silicon (a-Si:H) solar cells. To improve the performance of solar cells, textured front TCO is required as the optical layer which effectively scatters the incoming light and thus enhances the photon absorption within the device. One promising TCO material is aluminum-doped zinc oxide (AZO), which is most commonly prepared by magnetron sputtering. After deposition, sputtered AZO films are typically wet-chemically etched using diluted hydrochloric (HCl) or hydrofluoric (HF) acid to obtain rough surface morphologies. In this paper, we report the effects of a textured AZO front electrode on the performance of a-Si:H solar cells based on optical scattering modeling and electrical device simulations, involving four different AZO surface morphologies. The simulated light scattering behaviors indicate that a better textured surface not only scatters more light, but also allows more light get transmitted into the absorber (~90% of visible light), due to greatly reduced front reflection by the rough surface. Device simulation results show that the two-step AZO texturing process should give improved a-Si:H solar cell performance, with an enhanced short-circuit current density of 16.5 mA/cm2, which leads to a high photovoltaic (PV) efficiency of 9.9%. PMID- 27556995 TI - Design and daytime performance of laser-induced fluorescence spectrum lidar for simultaneous detection of multiple components, dissolved organic matter, phycocyanin, and chlorophyll in river water. AB - In this work, we developed mobile laser-induced fluorescence spectrum (LIFS) lidar based on preliminary experiments on the excitation emission matrix of a water sample and a method for reducing solar background light using the synchronous detection technique. The combination of a UV short-pulse laser (355 nm, 6 ns) for fluorescence excitation with a 10-100 ns short-time synchronous detection using a gated image-intensified multi-channel CCD of the fluorescence made the LIFS lidar operation possible even in daytime. The LIFS lidar with this construction demonstrated the potential of natural river/lake water quality monitoring at the Tenryu River/Lake Suwa. Three main components in the fluorescence data of the water, dissolved organic matter, phycocyanin, and chlorophyll, were extracted by spectral analysis using the standard spectral functions of these components. Their concentrations were estimated by adapting experimentally calibrated data. Results of long-term field observations using our LIFS lidar from 2010 to 2012 show the necessity of simultaneous multi-component detection to understand the natural water environment. PMID- 27556996 TI - Distributed dynamic strain measurement using optical frequency-domain reflectometry. AB - Distributed dynamic strain measurement based on optical frequency-domain reflectometry is proposed. The technique makes use of the wide scanning range of a tunable laser source in a short sweeping time, and subdivides the overall spectrum into narrower frequency windows. The advantage of subdividing the laser spectral range is to improve the measurement uncertainty induced by the laser wavelength difference between repeated scans. The noise-limited dynamic strain resolution is investigated experimentally, indicating that a minimum detectable strain is less than 200 nepsilon for a spatial resolution of 20 cm. By measuring the subdivided spectral shifts in the time sequence along the sensing fiber, the dynamic strain can be properly quantified over a 30 m measurement range for a highest sampling rate of up to 50 Hz. PMID- 27556997 TI - Digital holography-secured scheme using only binary phase or amplitude as ciphertext. AB - A digital holography-secured scheme is presented by using binary phase or amplitude. The input image is encrypted based on double random phase encoding, and a complex-valued wavefront in the charge-coupled device plane is extracted by using digital holography. Subsequently, only the phase component of the extracted complex-valued wavefront is maintained, and is further binarized. Different from conventional methods, an interesting finding in this paper is that in addition to binary phase, binary amplitude originating from the binarized phase pattern can also be applied as ciphertext. During optical decoding, the decrypted image cannot visually render clear information about the input, and the authentication is further conducted. The binary phase or amplitude pattern can be flexibly applied as ciphertext, and the fully optical approach can be implemented for the decoding. The ciphertext is effectively compressed, which can facilitate the storage and transmission in practical applications. PMID- 27556998 TI - Long-term phase-locking technique for locking the repetition rate of an optical frequency comb laser with 1.67 * 10-19 precision. AB - An ultrahigh stable phase-locked loop system for synchronization of an optical frequency comb to a hydrogen maser has been proposed and experimentally demonstrated. A mathematical model has been set up to investigate the feasibility and steady state of the phase-locking system. The fractional frequency instability is evaluated by measuring the mixed-phase signal of an improved experimental system. Experimental results show that the fractional frequency instability of the phase-locked loop system lies from 8.83*10-16 at 1 s to 1.67*10-19 at 1000 s, which indicates our proposed phase-locking system possesses ultrahigh measurement precision with good long-term stabilization performance. PMID- 27556999 TI - Graded-index thin-film stack for cladding and coupling. AB - A graded-index multilayer thin-film stack is optimized to act as a cladding layer on top of a silicon (Si) nanowaveguide and also a collimator for chip coupling where the waveguide ends. The numerical example shows an optimized graded-index profile from 2.35 to 1.45 provides an optical coupling to the standard single mode fiber with efficiency close to 90% while retaining tight light confinement for the Si nanowaveguide. The corresponding material realization of a graded index profile with a Si-rich nitride SiNx/SiON/SiO2 system is explored using inductively coupled plasma chemical vapor deposition, and a SiNx cladded Si waveguide is demonstrated. PMID- 27557000 TI - Influence of atmospheric turbulence on the properties of specular and antispecular beams. AB - A class of optical fields with specular or antispecular properties can be generated by a Gaussian Schell-model beam passing through a wavefront-folding interferometer. Based on the generalized diffraction integral formula, an analytical expression for the cross-spectral density function of such fields propagating through non-Kolmogorov atmospheric turbulence is derived. It is revealed that the specular and antispecular properties of the beams always maintain during propagation in free space. However, the specularity and antispecularity properties of the beams become different in atmosphere, since they are quickly destroyed by the atmospheric turbulence. PMID- 27557001 TI - Comparison of envelope detection techniques in coherence scanning interferometry. AB - The aim of this work is to make a comparison of the most current signal processing techniques used to analyze the fringe signal in coherence scanning interferometry (CSI), a major technique for optical surface roughness measurements. We focus here on classical AM-FM signal-processing algorithms such as the Hilbert transform (HT), the five-sample adaptive (FSA), and the continuous wavelet transform (CWT). We have recently also introduced a new family of compact and robust algorithms using the Teager-Kaiser energy operator (TKEO). We propose an improved version of TKEO using a combination of different techniques of pre filtering and demodulation processing to remove the noise and offset component and to retrieve the fringe envelope to either determine the surface height information or to separate adjacent transparent layers. In particular, as a pre filtering approach, we have focused on empirical mode decomposition in combination with the Savitzky-Golay filter. An added Gaussian post-filtering is helpful for a precise peak extraction. The experimental results show that TKEO performs better than CWT in terms of computation time and provides a better surface extraction than HT and FSA. Results have been obtained on synthetic and real data taken from a layer of resin on a silicon substrate. PMID- 27557002 TI - Design and analysis of a highly nonlinear composite photonic crystal fiber for supercontinuum generation: visible to mid-infrared. AB - A composite photonic crystal fiber structure has been designed with tellurite as the cladding and chalcogenide as a core material. To increase nonlinearity, rods of the chalcogenide glass material have been inserted around the core region. The reported structure offers very high nonlinearity of 1042 W-1 Km 1 at 2800 nm pump wavelength with low and flattened dispersion of approximately -11 ps.nm-1 Km-1. An effective mode area of 6.46 MUm2 of the propagating mode has been achieved as at pump wavelength. Such a highly nonlinear composite photonic crystal fiber structure is a potential candidate for nonlinear applications, such as slow-light and supercontinuum generation. Pumping at 2800 nm results in a supercontinuum spectrum spanning 0.5-4.7 MUm using 8 mm long photonic crystal fiber pumped with femtosecond laser pulses with peak power of 3 kW. PMID- 27557003 TI - Analysis of nodal aberration properties in off-axis freeform system design. AB - Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design. PMID- 27557004 TI - Qualitative research in the area of health: the whys and wherefores. PMID- 27557005 TI - The qualitative research article under scrutiny. PMID- 27557006 TI - Control of dengue: Consensus views of Endemic Disease Control Agents and Community Health Agents on their integrated action. AB - Dengue is one of Brazil's most important public health challenges. Activities for its prevention and control have been based on the strategy of integrated management proposed in health policies, in which the central actors are the Endemic Disease Control Agent(ACE) and the Community Health Agent (ACS). This study analyzes consensus opinions produced by ACSs and ACEs on theactions for incorporating ACEs into the teams of the Family Health Strategy (ESF). It is a qualitative study from a large municipality in Brazil in which dengue is endemic, using a focus group of professionals that is subsequently analyzed using Collective Subject Discourse Analysis, supported by WebQDA. The results indicate consensus positions in relation to the following subjects: I) difficulty in the process of integration of ACSs and ACEs for control of dengue; II) inclusion of ACEs in the primary healthcare of the ESF; and III) absence of monitoring and assessment of the integrated actions. In conclusion, there are needs: to make participants more aware, seeking changes in behavior; to offer an environment of support to those involved with training courses about dengue; and to monitor the process of integration, and evaluate it periodically, creating indicators of quality and quantity. PMID- 27557007 TI - Expectations of a group of Portuguese pregnant women in the districts of Viseu and Aveiro regarding motherhood. AB - Motherhood is a complex phenomenon, supplementedwith expectations about the new reality, the hopes of all going well, taking into account the expected care. In order to meet the needs of the Portuguese expectant mother, it is necessary to know what she deems essential for herself and her family, so that strategies may be developed to facilitate the transition process. This study was intended to gain insight into fulfilled and unfulfilled expectations of health care in motherhood with a group pregnant females in Portugal. This is a qualitative, exploratory and descriptive study, with 22 Portuguese women belonging to the Clusters of Health Care Centers of the districts of Viseu and Aveiro. The data was collected through semi-structured interviews and analysed using content analysis proposed by Bardin, supported by QSR NVivo 10. It was observed that fulfilled expectations surpassed those unmet, especially in terms of high quality health care and competent health care professionals. Regarding unfulfilled expectations, they mainly refer to maternity incentives, with an emphasis on the wish of greater financial familly supportfrom the government. PMID- 27557008 TI - Can institutional videos contribute towards the debate on how to deal with domestic violence against children? AB - Violence is increasing worldwide mainly among the most socially vulnerable groups such as women, elderly people, children and adolescents. In addition to the justice sector, many other areas and workers are involved and they are becoming even more important for addressing violence. One such area is the health sector. This article aims to identify the creative potential of videos that aim to tackle issues involving domestic violence against children which are categorized based on generation (age) and gender. A search was conducted between 2013 and 2014 on official sites and video channels of institutions that deal with child-related topics. We used the webQDA software to conduct our analysis and for reference purposes we used "Generation" and "Gender" as categories. We collected 40 video campaigns, of which ten were analyzed qualitatively. Upon analyzing complete scenes and parts of scenes we were able to see both inter/intra -generational and inter/intra-gender violence and its consequences for children. The videos allowed for critical reflections to be made on the educational processes and training used to combat violence against children in the context of "Generations" and "Genders". PMID- 27557009 TI - Factors connected with professional satisfaction and dissatisfaction among nutrition teacher. AB - Teacher satisfaction can be reflected in the success of higher education institutions to provide meaningful learning to their students. This study analyzed the professional satisfaction of nutrition teachers at a federal institution of higher education by identifying the factors that generated satisfaction and dissatisfaction for them and also the feelings that they envisioned for themselves at the end of their careers. This is a descriptive and exploratory study with a qualitative approach. A questionnaire and semi structured interviews were performed. The results showed that 72.7% of the teachers were satisfied with their profession. In relation to satisfaction were considered: the fulfillment of a vocation; research and extension activities; the development and recognition of students and society; learning; autonomy; flexibility; and relationships with students. In relation to dissatisfaction were considered: overloading due to work, administration, bureaucratic duties and assistance; lack of interest and respect from students; relationships with colleagues and managers; devaluation in the role of teaching; large classes and poor physical infrastructure. The respondents expressed a positive attitude and had no desire to leave their profession. Further studies are required regarding factors leading to satisfaction and dissatisfaction for teachers, in order to contribute to their productivity and well-being. PMID- 27557010 TI - [Qualitative analysis of topics related to the quality of life of people with disabilities]. AB - Quality of life is a concept that reflects the subjective perception of individuals in relation to their degree of satisfaction with their living conditions. It is a concept that involves putting the individual at the forefront, talking about the quality of the professionals involved and influencing the development of programs and the provision of services. The article reflects the opinions that different agents have in relation to disability on given topics related to the model of quality of life such as: the relationship between different agents; the necessary training of professionals in the field of health and/or disability; and the existence of the presence of the participation in society of people with disabilities. Using qualitative methodology, the arguments of the participants in these three issues are discussed. The verbiage, the conceptual map and the analysis of content, performed after the encoding of information, made it possible to detect the perceived needs and satisfaction with the care of the different services. The profile of the qualified professional within the scope of disability is outlined. Proposals for the future are contained in the conclusions, ensuring the improvement of the quality of life of people with disabilities. PMID- 27557011 TI - Bond between nurses and mothers of children younger than two years: perception of nurses. AB - To promote child health during nursing consultations, it is essential that nurses establish bonds with mothers to guide them in childcare. The present study attempted to identify a possible bond during nursing consultations between the nurses who work in the Family Health Strategy and the mothers of children who are younger than two years old. This qualitative study was conducted in seven Family Health Units in the city of Joao Pessoa, in the state of Paraiba (PB), Brazil, between May and November 2013, through semi-structured interviews with nurses. The thematic analysis allowed the identification of relevant themes, namely, (1) the elements that create bonds and (2) the difficulties in the establishment of a bond. The nurses realize that in primary care, relationships are based on intersubjectivity. By acting within the concept of individual care, the nurses provide individualized and humanized care and believe that bonds are essential for comprehensive care. However, the nurses have difficulties in establishing bonds, and they attribute these difficulties to the high demand for care and the difficulty in giving continuity to the mothers' presence in the health care unit. PMID- 27557012 TI - Limits and possibilities of an online game for building adolescents' knowledge of sexuality. AB - This study looks at the limits and possibilities of an online game designed to build knowledge and awareness in adolescents in the field of affections, sexuality and reproduction. It evaluates the experience of a group of teenagers with a game called Papo Reto ('Straight Talk'), over a period of three months. A total of 23 teenagers aged 15 to 18 took part in the study. The data were collected in two workshops held at a secondary school in the city of Sao Paulo (Sao Paulo State), Brazil. The dialogs were recorded and transcribed, and their content analyzed. The results showed a variety of possibilities of the Straight Talk online game for reconstruction of knowledge in the field of sexuality, and for helping the subject perceive and analyze the complexity of reality from a gender point of view. The subjects covered in the game were assessed, as motivating factors for the game and for the interaction. Adjustments were suggested for inclusion of elements to create a more ludic quality, more interaction, in the game. PMID- 27557013 TI - The McGill Illness Narrative Interview - MINI: translation and cross-cultural adaptation into Portuguese. AB - This paper presents the process of translation and cultural adaptation into Portuguese of the McGill Illness Narrative Interview - MINI, an interview protocol that is used to research meanings and modes of narrating illness experiences, tested, in the Brazilian context, for psychiatric and cancer-related problems. Two translations and their respective back-translations were developed. In addition, semantic equivalence was evaluated, a synthesis version and a final version were prepared, and two pre-tests were administered to the target populations (people with auditory verbal hallucinations or breast cancer). A high degree of semantic equivalence was found between the original instrument and the translation/back-translation pairs, and also in the perspective of referential and general meanings. The semantic and operational equivalence of the proposed modifications was confirmed in the pre-tests. Therefore, the first adaptation of an interview protocol that elicits the production of narratives about illness experiences has been provided for the Brazilian context. PMID- 27557014 TI - Medellin youth experiences before, during and after belonging to an illegal armed group, 2005. AB - A better understanding of the experiences of young people before, during and after belonging to an illegal armed group (IAG) can provide information to promote their reintegration into urban settings in Colombia and to help prevent violence. A qualitative study with a hermeneutic historical approach was performed to examine these experiences from the perspective of direct or indirect participants in the armed conflict. Fifty individuals aged 14-24 years (7 women and 43 men) with low socioeconomic status from Medellin were interviewed; 26 of them had a history of direct experience with IAGs. What stands out in their stories are descriptions of obstacles to progress in their lives; lives marked by stigma, poverty, violence and inequality; the differences of opinion among these young people regarding whether to belong to these illegal groups; how becoming an active member of an IAG creates both an opportunity for the present and an additional obstacle for the future, which adds complexity to the risk behaviors they assume; and how the reintegration process offers new expectations regarding access to educational and employment opportunities and social recognition. All of these factors point to the need for not only a comprehensive reintegration process but for more inclusive and equitable social policies, in this case for children and young people. PMID- 27557015 TI - [Aging at home with telecare in Spain. A dicourse analysis]. AB - Caring for the elderly is turning to forms of community care and home care. Telecare is one of those emergent modalities of caring. This article will explore the meanings that older people give to the experience of staying at home in later life by using telecare. Discourse analysis is used to examine a set of focus groups and interviews with telecare users from different cities of Catalonia (Spain). The outcomes include three interpretative repertoires that we called: "Aging at home", "normal aging" and "unsafe aging". For each repertoire we examine how the permanence of older people in their homes is accounted, and which role telecare plays in such experience. PMID- 27557016 TI - Communication strategies employed by rare disease patient organizations in Spain. AB - The current study focuses on communication strategies employed by rare disease patient organizations. The aims of these organizations are: educate and inform the public about rare diseases, raise awareness of the problems related to rare diseases, and achieve social legitimacy in order give visibility to their demands. We analyzed the portrayal of rare disease and patient organizations by Spain's major media organizations in terms of circulation and viewership - the press (El Pais, El Mundo, La Vanguardia,ABC and El Periodico), radio (CadenaSer, Onda Cero, Cope and RNE), and television (Telecinco, Antena 3, La 1, La Sexta, Cuatro) -between 2012 and 2014.We then carried out a descriptive analysis of communication activities performed via the World Wide Web and social networks by 143 national organizations. Finally, we conducted a telephone questionnaire of a representative sample of 90 organizations in order to explore the association between media presence and funding and public image. The triangulation of quantitative and qualitative methods allowed us to meet the study's objectives. Increased visibility of the organizations afforded by an increase in the coverage of the topic by the medialed to an increase in membership - but not in donations and increased awareness of these diseases. PMID- 27557017 TI - [Youths in the shantytowns (favelas) of Rio de Janeiro/Brazil: from social vulnerability to opportunities for human development]. AB - Based on a review of living conditions in the complex and dynamic reality of the shantytowns ("favelas") of Rio de Janeiro and the main difficulties facing the human development of youths in this context, we analyze the social protection function involved in educational projects that offer new opportunities for life. In this article we analyze the relationship between the variables of social exclusion, poverty and violence, jointly grouped in the social vulnerability category, and the variables related to opportunities for human development grouped in the resilience category. The socio-educational projects constitute an important factor of resilience, able to influence the subjective development of young people and impact the improvement in the quality of life in the favelas. The social recognition and the relationship of trust established with educators and other youths in similar situations foster efforts to develop changes in attitude and to build new possibilities of life in spite of social vulnerability. The opportunity to experience interpersonal relationships, emotional bonds and positive social interaction can promote changes in the world view of youths and elicit a desire to change their living conditions and enhance their projects for the future. PMID- 27557018 TI - [New possible determinants of the quality of life of patients with treated thyroid cancer: a qualitative study]. AB - The aim of this study was to develop a qualitative approach of determinant factors of the quality of life of treated patients with papillary thyroid carcinoma. Sixteen in-depth interviews were conducted with individuals 18 to 45 years old regarding their disease representations and experiences, followed by statements content analysis. The results show issues already provided in structured questionnaires about quality of life, although others were only partially assumed in these surveys (management of the concept of disease etiology; the "forced" patient introduction into the medical conceptual universe; the fear of the prognosis and positive changes in lifestyle). The results interpretation were benefited from recently developed theoretical elaborations: the anxieties related to illness experience seem to be configured as a "modern risk", in the context of a "risk society". The development of structured questionnaires on quality of life requires frequent qualitative studies to capture changes in subjective aspects of the construct, given the dynamic changes of historical, cultural and psychological meanings of the health disease process, constantly influenced by technological innovations and continuing epidemiological interpretations. PMID- 27557019 TI - [Therapeutic itineraries of individuals with symptoms of anorexia and bulimia]. AB - The scope of this study is to identify and contextualize aspects of the therapeutic itineraries of patients treated at a university medical clinic specialized in nervous anorexia and bulimia. For this purpose, an attempt was made to reconstitute the succession of events triggered in 20 respondents and their families with the classification of anorexia and bulimia as "health problems." The narratives were analyzed in order to link the individual experiences and the social context of their occurrence (organization of health services, characteristics of treatment and medical knowledge and characteristics of contemporary subjectivity), in light of the theoretical studies of Public Health and Psychoanalysis. Data analysis revealed that these itineraries arise from connections and disconnections between two distinct approaches: one that organizes the management of patients and the other governing the conduct of health institutions and families. If the latter presuppose a quest for health, this is not what primarily concerns the individuals in question. Their refusal to moderate their own eating disorders is notable on their itineraries, and indicates the functionality of those practices. Such practices play a part in the reconstruction of their self-images. PMID- 27557020 TI - To donate or not donate, that is the question: an analysis of the critical factors of blood donation. AB - Currently, in Brazil, 1.78% of the population area blood donors, a level lower than the ideal one that, according to WHO, should be between 3% and 5% of the population. Following this scenario, the current study has a general goal of identifying and analyzing the main critical factors of the process of blood donation in the city of Belo Horizonte, MG, under the perception of donors, potential donors and non donors. A qualitative research approach was conducted, through twenty-four semi-structured interviews. The results highlight the lack of information in the various stages of the blood donation system. During the stages of donor recruitment and awareness, communication actions convey to society incomplete information about the donation process, discouraging future actions of donation. On the other hand, a lack of appreciation of the donation experience and the construction of social values associated with the donor prevent the multiplication of social behaviors for donation. The results of this study, found from theoretical framework outlined in this study, highlight the causes or critical factors that impede changes in behavior, incremental or radical, proposed by social marketing. PMID- 27557021 TI - Decision making and senior management: the implementation of change projects covering clinical management in SUS hospitals. AB - This paper analyses the decision making process for senior management in public hospitals that are a part of the National Health Service in Brazil (hereafter SUS) in relation to projects aimed at changing clinical management. The methodological design of this study is qualitative in nature taking a hermeneutics-dialectics perspective in terms of results. Hospital directors noted that clinical management projects changed the state of hospitals through: improving their organizations, mobilizing their staff in order to increase a sense of order and systemizing actions and available resources. Technical rationality was the principal basis used in the decision making process for managers. Due to the reality of many hospitals having fragmented organizations, this fact impeded the use of aspects related to rationality, such as economic and financial factors in the decision making process. The incremental model and general politics also play a role in this area. We concluded that the decision making process embraces a large array of factors including rational aspects such as the use of management techniques and the ability to analyze, interpret and summarize. It also incorporates subjective elements such as how to select values and dealing with people's working experiences. We recognized that management problems are wide in scope, ambiguous, complex and do not come with a lot of structure in practice. PMID- 27557022 TI - It's like a family: the significance attributed by health professionals to diabetes health education groups. AB - This article analyzes the significance that health professionals attribute to health education groups for people with Type 2 Diabetes Mellitus (T2DM). This ethnographic study was developed with five professionals from an Expanded Family Health team that operated in five diabetes health education groups. Information was gathered using participant observations and semi-structured interviews. Data were analyzed by means of a thematic coding technique. Three different categories emerged: (1) It is a way of educating them: groups as an educational and clinical monitoring forum; (2) they know I will be there for them: the groups as a resource to access the health system; and (3) this serves as a self-help group: after all, what purpose does this group serve? The conclusion reached is that the groups studied were a therapy and support hybrid that, by means of their structure, made it possible for the informants (perhaps, also for the patients) to construct other significance for the standardization of health policies and the dilemma of chronicity. Such hybridization made it possible to create outcomes for the specificities of health work in a "total life" context. PMID- 27557023 TI - School meals defined from the perspective of students catered for under the National School Feeding Program, Brazil. AB - Based on socio-anthropological studies into food and in connection with guidance from the Public Policy on Food and Nutrition Security in Brazil, this paper sought to objectively analyze students' views of the school meals given to them as part of the National School Feeding Program (PNAE). The data was produced through ethnographic exercises that were developed where the above Program (hereafter Program) had been implemented in a semi-arid municipality in the state of Bahia. The exercises also involved the production of written material and the use of focus groups with teenagers in primary school education. Of particular note in this study was the time and space the students had for their break/recreation period which brought to light the relationship between the body and food. Based on the responses given we were able to identify different understandings and meanings associated with the food served in these institutions. The study helped to shed some light on the relational aspects between habitual eating at "home-on the road-and-in school" with the right to have school meals. We were also able to obtain a broader understanding of the eating habits of teenagers that are catered for as part of the PNAE. PMID- 27557024 TI - Difficulties experienced by trans people in accessing the Unified Health System. AB - The objective of this study was to discuss the difficulties of trans people living in the metropolitan region of Greater Vitoria, Espirito Santo, Brazil, in accessing the health services of the Unified Health System (Sistema Unico de Saude - SUS). We used a qualitative approach through semi-structured interviews with 15 trans people. The results point to disrespect toward the adopted name, discrimination, and the diagnosis required for the gender reassignment process as major limitations to accessing the healthcare system. The diagnosis helps hide the responsibility of heteronormativity and gender binarism in the social marginalization of trans people. It is concluded that it is necessary to review the issue of diagnosis, given that the existence of a prior pathology is not required to access the SUS. It is important to develop educational programmes and permanent campaigns concerning the right to access the healthcare system free from discrimination and to use the adopted name. PMID- 27557025 TI - [Knowledge of nurses and incentive strategies for family participation in breastfeeding]. AB - This study sought to analyze the knowledge of nurses about the benefits of breastfeeding for the family and describe the inclusion of family involvement in health activities associated with breastfeeding. A qualitative, exploratory and descriptive study was conducted with 8 nurses in the municipality of Itapetinga in the state of Bahia in the first semester of 2014. Semi-structured interviews were used for data gathering and the thematic content analysis technique was used for processing the data. It was found that awareness of nurses about the benefits of breastfeeding for the family corresponds to the information released by the Ministry of Health and to the data found in the literature. This includes the promotion of maternal and child health and the strengthening of emotional bonds. It should be stressed that there was no mention about the advantages of breastfeeding as a natural method of family planning. With respect to family inclusion in breastfeeding, it was found that nurses use the actions of health education and puerperal and home visits as a strategy, emphasizing the trials and difficulties of a family nature. Health professionals should encourage this participation, in an attempt to work together with family members so that they feel active participants and recognize their importance in this process. PMID- 27557026 TI - Is the value of Community Healthcare Agents in Brazil's Family Health Strategy receiving full recognition? AB - This paper discusses meanings produced by Community Healthcare Agents (ACSs) on whether or not they feel that ACSs in Brazil's Family Health Strategy are receiving the recognition they deserve, considering their work with social networks. Discussion groups with 28 agents of six Health Units were held, sound recorded and transcribed. Qualitative analysis of the material enables us to identify, in the discursive practices of ACSs, a tension on whether proper value is attributed to their work, or not. There was attribution of value when they talk of their activity in close proximity with the community, and their potential for construction of human connections; but there was non-attribution of value when they talk of the system's macro-structural aspects, such as low salaries, and low recognition of their function, in comparison to higher-level professionals. We conclude that the view of their work - still involving fragmented work processes, and expectation by the population that they will be able to provide immediate solutions to demands - might be preventing them from taking on board a more wide-ranging concept of primary healthcare, as a structuring and communication agent of the Healthcare Network, and as an organizing agent of Brazil's Unified Health System. PMID- 27557027 TI - Innovation in the role of the Office of the Ombudsman of the Unified Health System (SUS) - reflections and potential benefits. AB - This article seeks to reflect on the potential of innovative practices in the design and work of the government bodies that comprise the National System of Offices of the Ombudsman of the Unified Health System. It is divided into two parts, seeking to answer the following question: How to think of and implement innovative practices - which include sustainability - when the people are voicing their urgent demands and these are being heard by the public authorities? These grievances are all the more urgent as they involve the area of Health and can they be promptly discussed, attended and resolved? In the first part, the article discusses the polysemic concept of innovation, focusing on its application in the three spheres of public administration, and highlights the importance of its close correlation with the different notions of information and knowledge in a society such as the one we live in. In the second, it develops a task-force of ideas for the office of the ombudsman and based on this, a draft operational concept of innovation in the role of the office of the ombudsman, considering the context of high speed change and transformations and the complexity inherent to contemporary life and the need for resource management and expertise development in information management. PMID- 27557028 TI - [Possibilities of inclusion of the partner in deliveries in public institutions]. AB - Qualitative research, with an exploratory and descriptive approach, was conducted between September 2011 and February 2012, aimed at revealing the possibility of inclusion of the partner in deliveries in institutions that currently restrict their presence. Twelve nurses responsible for obstetric centers and five technical directors of health institutions of Santa Catarina, who did not allow or infrequently allowed the presence of the partner during delivery, were interviewed. Data were analyzed using Bardin Content Analysis, with the support of ATLAS.ti software. The possibilities of including the partner are permitted in three categories: I - Labor pain process; II - Receptiveness of professionals to the partner; and III - Empowerment of patients. Although some institutions limit the presence of the partner, they describe aspects that favor their inclusion. From the results presented, it is suggested that these enabling elements could be bolstered with management strategies, ongoing learning and intersectoral actions. PMID- 27557029 TI - Independent Life Skills among psychosocial care network users of Rio Grande do Sul, Brazil. AB - This is a cross-sectional study that aims to identify the prevalence of lower independent living skills and their associations in 390 users of psychiatric community-based services in the state Rio Grande do Sul, Brazil. For tracing the outcome it was used the "scale Independent Living Skills Survey", adopting a cut off value lower than 2. The crude and adjusted analyses were conducted on binary logistic regressions and they considered a hierarchical model developed through a systematic literature review. In adjusted analysis the level of the same variables were adjusted to each other and to previous levels. The statistical significance remained as a < 0.05 p-value. The prevalence of smaller independent living skills was 33% and their associations were: younger age; no partner; lower education; resident at SRT; diagnosis of schizophrenia and younger diagnosis. PMID- 27557030 TI - [Anemia in indigenous women and children in Brazil: a systematic review]. AB - Iron-deficiency anemia can be considered the most important nutritional deficiency in Brazil. The scope of this article was to conduct a systematic review of the literature in order to describe the frequency of anemia in indigenous women and children in Brazil, and gather information on associated factors. A search of the PubMed, Scopus and Lilacs databases was conducted. Seventeen studies were selected. The rates of prevalence of anemia ranged from 23.1%-74.6%; 42.9%-92.3% and 29.6%-84%, for children aged 6 to 119 months, 6 to 23 months and 6 to 59 months, respectively. Two studies were conducted with women of childbearing age and rates of 67% were found among the Surui and 16.1% among the Xukuru of Ororuba. The majority of authors attribute the prevalence of anemia to inadequate sanitary conditions, diets deficient in iron and essential micronutrients and a lack of access to basic health services. The findings highlight the importance of anemia among the indigenous peoples studied, which has been reflected by a substantial increase in research over the last twenty years. PMID- 27557031 TI - [Parental roles and needs in neonatal intensive care: a review of Portuguese guidelines]. AB - The scope of this article is to analyze the parental roles and needs included in Neonatal Intensive Care Unit guidelines. Thematic content analysis was conducted of 33 guidelines (28 consensuses and 5 documents directed to parents) freely available on the Portuguese Pediatrics Society website in August 2014. These documents deal mainly with information needs, child care activities performed by the parents and the respective responsibilities in decision making with respect to the health of children. Furthermore, parental and family characteristics were mentioned as risk factors for prematurity and perinatal diseases. The psychosocial consequences of parenthood experienced in Neonatal Intensive Care Units, as well as the adequacy of their environmental characteristics to parental needs, were less frequently touched upon. Issues related to the safety and comfort, confidence of parents in healthcare and social support were rarely touched upon. The results reflect sociocultural norms associated with intensive parenting, which is exclusively child centered, highly emotional and performed under the guidance of health professionals. The important aspect is to issue and disseminate guidelines that foster the integration of family-centered care in the dynamics of Neonatal Intensive Care Units. PMID- 27557032 TI - Homeless people's right to health: reflections on the problems and components. AB - In the present context of neoliberalism, it can be seen that employment and family links are becoming more fragile, contributing to the phenomenon of social exclusion, and making people who are homeless - the Homeless - more visible. This population, situated on the margin of the healthcare network, challenges the universality, equity and integrated quality of Brazil's Unified Health System - the SUS, and has been the subject of focalizing policies. The debate on this theme is the subject of this study, which is an integrative review of Brazilian publications in the literature databases of Lilacs (Latin America and the Caribbean Health Sciences Database) and the BDENF (Base de Dados de Enfermagem - Nursing Database), to provide a survey of the literature on characterization of the Homeless as a group, their needs and the policies that have been developed to serve them. The study reveals that discussion on the homeless has been timid in production of knowledge, principally in relation to comprehension of the social determinants of the health-disease process of this group. The social policies addressing this population are, mostly, compensatory and existentialist, so that they do not allow for materialization of the right to health as a possible outcome. In this context, it becomes necessary to build social policies that are coherent with the social needs of the homeless. PMID- 27557033 TI - Towards a community mental health care for people with schizophrenia in Colombia. AB - Mental health care based on the community has shown to be effective and successful for the health care service to people with severe mental disorders such as schizophrenia, evidence that is less clear in the health care system in Colombia, where weaknesses are present, both for prevention and rehabilitation, although national guidelines give importance to the social context in relation to the disease. As a contribution to the discussion on providing care for people living with schizophrenia, a topic review was conducted with the aim of identifying experiences in community mental health care services, in relation to their relevance to these people at the national level. Articles were searched on Scientific Electronic Library Online (SciELO) Medline with Full text, Science Direct and documents of the World Health Organization, Pan American Health Organization and the Colombian Ministry of Health and Social Protection. Few experiences in community care for people with schizophrenia in Colombia were found and given its importance to public health worldwide, a call for attention is made towards the construction and implementation of these models in the Colombian context. PMID- 27557034 TI - Approval of the Resolution governing the ethics of research in social sciences, the humanities, and other disciplines that use methodologies characteristic of these areas: challenges and achievements. PMID- 27557035 TI - [Jose Lima Pedreira de Freitas and the redefinition and control of Chagas disease]. AB - A brief overview of the evolution of knowledge about Chagas disease since its discovery by Carlos Chagas in 1909 until the mid-1940s is presented. The trajectory of physician Pedreira de Freitas and his growing involvement in research in the area led to his contributions to laboratory diagnosis - which lent consistency and security to epidemiological surveys of Chagas disease - and the redefinition of the scale of the disease in Brazil and the Americas with its terrible social and economic impact. His proposal for the disease prevention model - based on selective purging in the application of insecticide - was adopted nationally and internationally and made it possible to bring the disease under control in Brazil and other countries. He devoted himself with equal intensity to enhancing the teaching of medical practices in the community and was a pioneer in the implementation of preventive medicine in medical education in Brazil. PMID- 27557036 TI - ? AB - [This corrects the article doi: 10.1590/1413-81232015213.06472015] [This corrects the article doi: 10.1590/1413-81232015216.07672016] [This corrects the article doi: 10.1590/1413-81232015216.08752016] [This corrects the article doi: 10.1590/1413-81232015216.08172016]. PMID- 27557037 TI - Theoretical Assessment of Fluorinated Phospholipids in the Design of Liposomal Drug-Delivery Systems. AB - Fluorinated phospholipid analogues are investigated as potential substrates for phospholipase A2 (PLA2) using classical molecular dynamics simulations and quantum mechanics/density functional theory calculations. The fluorinated phospholipid analogues are alpha-fluoro (HF-ProAEL) and alpha,alpha-difluoro (F2 ProAEL) conjugates of (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3 phoshocholineglycerol (ProAEL). Our results provide a theoretical assessment of the potential usefulness of these fluorinated lipids in the rational design of liposomal drug-delivery systems. The alpha-fluorine-substituted phospholipid analogues are found to be substrates for secretory PLA2, with sufficient accessibility of water to the active site to allow for enzymatic hydrolysis. Because of the inherently less stable nature of HF-ProAEL and F2-ProAEL when compared to that of ProAEL, the hydrolytic reaction is predicted to occur at a progressively faster rate; the more electronegative substituent at the alpha position effectively lowers the energy barrier for hydrolysis. We conclude that the partially fluorinated phospholipid analogues facilitate rational design of liposomal vesicles of phospholipid mixtures with desirable physicochemical properties and that are still subjects for important and pharmaceutically proven drug-delivery mechanisms. PMID- 27557038 TI - Metal-based ethanolamine-derived compounds: a note on their synthesis, characterization and bioactivity. AB - Metal-based ethanolamines, (L1)-(L4) coordinated with Co(II), Cu(II), Ni(II) and Zn(II) metals in 1:2 (metal:ligand) molar ratio to produce new compounds have been reported. These compounds were screened for their bactericidal/fungicidal activity against a number of bacterial (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata) alongside against a shrimp species known as Artemia salina. The screening results indicated that metal complexes have significantly higher activity than uncomplexed ligands against one or more bacterial/fungal species due to chelation. The ligand (L4) displayed good bacterial and fungal activity as compared to other ligands. The antibacterial results revealed that the Zn(II) complex (16) of (L4) was found to be the most active complex and Co(II) complex (14) of the same ligand (L4), demonstrated the highest antifungal activity. PMID- 27557039 TI - Mixed-Methods Study of Uptake of the Extension for Community Health Outcomes (ECHO) Telemedicine Model for Rural Veterans With HIV. AB - PURPOSE: Extension for Community Health Outcomes (ECHO) is a provider-level telemedicine model successfully applied to hepatitis C care, but little is known about its application to Human Immunodeficiency Virus (HIV) care. We performed a mixed-methods evaluation of 3 HIV ECHO programs in the Veterans Health Administration, focusing on uptake by primary care clinics and veterans. METHODS: Administrative data were used to assess program uptake, including adoption (ie, proportion of primary care clinics participating) and reach (ie, proportion of eligible veterans participating). Veterans were considered eligible if they had an HIV diagnosis and lived nearer to a primary care clinic than to the HIV specialty clinic. We interviewed 31 HIV specialists, primary care providers (PCPs), and administrators engaged in HIV ECHO, and we analyzed interview transcripts to identify factors that influenced program adoption and reach. FINDINGS: Nine (43%) of 21 primary care clinics adopted HIV ECHO (range 33%-67% across sites). Program reach was limited, with 47 (6.1%) of 776 eligible veterans participating. Reach was similar among rural and urban veterans (5.3% vs 6.3%). In interviews, limited adoption and reach were attributed partly to: (1) a sense of "HIV exceptionalism" that complicated shifting ownership of care from HIV specialists to PCPs, and (2) low HIV prevalence and long treatment cycles that prevented rapid learning loops for PCPs. CONCLUSIONS: There was limited uptake of HIV ECHO telemedicine programs in settings where veterans historically traveled to distant specialty clinics. Other telemedicine models should be considered for HIV care. PMID- 27557040 TI - Two light-activated neuroendocrine circuits arising in the eye trigger physiological and morphological pigmentation. AB - Two biological processes regulate light-induced skin colour change. A fast 'physiological pigmentation change' (i.e. circadian variations or camouflage) involves alterations in the distribution of pigment containing granules in the cytoplasm of chromatophores, while a slower 'morphological pigmentation change' (i.e. seasonal variations) entails changes in the number of pigment cells or pigment type. Although linked processes, the neuroendocrine coordination triggering each response remains largely obscure. By evaluating both events in Xenopus laevis embryos, we show that morphological pigmentation initiates by inhibiting the activity of the classical retinal ganglion cells. Morphological pigmentation is always accompanied by physiological pigmentation, and a melatonin receptor antagonist prevents both responses. Physiological pigmentation also initiates in the eye, but with repression of melanopsin-expressing retinal ganglion cell activity that leads to secretion of alpha-melanocyte-stimulating hormone (alpha-MSH). Our findings suggest a model in which eye photoperception links physiological and morphological pigmentation by altering alpha-MSH and melatonin production, respectively. PMID- 27557041 TI - LOW-FIELD MAGNETIC RESONANCE IMAGING APPEARANCE OF POSTARTHROSCOPIC MAGNETIC SUSCEPTIBILITY ARTIFACTS IN HORSES. AB - An awareness of magnetic susceptibility artifacts is important for interpreting prepurchase and postoperative magnetic resonance imaging (MRI) studies in horses. These artifacts occur when a metallic or a paramagnetic substance creates a local magnetic field deformity. Aims of the current experimental study were to determine prevalence of these artifacts after arthroscopy in a sample of nonlame horses, and to describe effects of time and type of pulse sequence on low-field MRI signal intensity and detection of the artifacts. Ten, nonlame Standardbred horses were prospectively recruited. All horses underwent arthroscopy of both metacarpophalangeal joints for purposes unrelated to the study. Serial low-Field MRI examinations were performed on each horse and each joint (before, and 6 and 12 weeks postsurgery). In two horses, more detailed longitudinal evaluations were performed with additional MRI examinations. Magnetic susceptibility artifacts were detected postoperatively at the surgical access sites in eight metacarpophalangeal joints at both 6 and 12 weeks after surgery (40% prevalence). Neither of the two longitudinally followed horses had artifacts at any time. Artifacts were only detected on gradient echo (GRE) sequences. Findings indicated that magnetic susceptibility artifacts can be present in postarthroscopy MRI studies in horses and can persist up to 12 weeks after arthroscopy. For this sample of horses, the artifacts did not interfere with evaluation of the joint. Further longitudinal studies are needed to determine the full duration of magnetic susceptibility artifact persistence in affected tissues. PMID- 27557042 TI - Speech effects of Hawley and vacuum-formed retainers by acoustic analysis: A single-center randomized controlled trial. AB - OBJECTIVE: To investigate the effects of alteration on speech articulation of adult patients between Hawley retainers and vacuum-formed retainers by an objective acoustic analysis of vowels and voiceless fricatives. MATERIALS AND METHODS: Twenty adults, aged 19.0-29.0 years, who had just finished active orthodontic treatment were included in this study. They were divided into a Hawley retainer group and a vacuum-formed retainer group by sortation randomization method. The assessment of speech sounds was performed objectively using acoustic analysis before and after retainer application at the following time points: before wearing (T0), immediately after wearing (T1), and at 24 hours (T2), 1 week (T3), 1 month (T4), and 3 months (T5). RESULTS: The production of /ze:/, /i:/, /f/, /theta/, /s/, and /?/ sounds for the Hawley retainer group and /i:/, /theta/, /s/, and /?/ sounds for the vacuum-formed retainer group showed severe speech impairment according to acoustic analysis (P < .05). A comparison of the Hawley retainer group with the vacuum-formed retainer group revealed that the performance of /i:/, /f/, and /s/ sounds were significantly different (P < .05). CONCLUSION: Although sound distortion could be found in both the Hawley retainer group and the vacuum-formed retainer group, changes in articulation were more obvious in the Hawley retainer group. PMID- 27557043 TI - Process-relevant concentrations of the leachable bDtBPP impact negatively on CHO cell production characteristics. AB - The biopharmaceutical industry has invested considerably in the implementation of single-use disposable bioreactors in place of or in addition to their stainless steel-counterparts. This new wave of construction materials for disposable bioprocess containers encompass a plethora of uncharacterized secondary compounds that, when in contact with the culture media, can leach, contaminating the bioprocess. One such cytotoxic leachable already receiving attention is bis(2,4 di-tert-butylphenyl)-phosphate (bDtBPP), a breakdown product of the secondary antioxidant Irgafos 168 in polyethylene-film based bags. This compound has been demonstrated to inhibit cell growth at concentrations ranging from 0.12 to 0.73 mg/L across an array of cell lines. Here we demonstrate that a further two CHO cell lines exhibit sensitivity to bDtBPP exposure at concentrations lower than that previously reported (0.035-0.1 mg/L). Furthermore, these inhibitory concentrations reflect bDtBPP levels found to leach early into the bioprocess, exposing reactor inoculums to serious risk. Quantitative label-free LC-MS/MS revealed that irrespective of cell line or concentration of bDtBPP, 8 proteins were found to be commonly differentially expressed in response to exposure to the compound highlighting biological processes related to cellular stress. Although the glycoprofile of the recombinant antibody remains primarily unchanged, we demonstrate that this compound when spiked at meaningful concentrations 72 h into culture considerably reduces the maximum cell density achieved. Studies like this reinforce the requirement for the complete characterization of all potential leachable compounds from disposable materials to assess their risk not only to the patient but also to the production pipeline itself. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1547-1558, 2016. PMID- 27557044 TI - Correction: Grasping Hand Verbs: Oscillatory Beta and Alpha Correlates of Action Word Processing. AB - [This corrects the article DOI: 10.1371/journal.pone.0108059.]. PMID- 27557045 TI - Quantum Dot/Light-Emitting Electrochemical Cell Hybrid Device and Mechanism of Its Operation. AB - A new type of light-emitting hybrid device based on colloidal quantum dots (QDs) and an ionic transition metal complex (iTMC) light-emitting electrochemical cell (LEC) is introduced. The developed hybrid devices show light emission from both active layers, which are combined in a stacked geometry. Time-resolved photoluminescence experiments indicate that the emission is controlled by direct charge injection into both the iTMC and the QD layer. The turn-on time (time to reach 1 cd/m(2)) at constant voltage operation is significantly reduced from 8 min in the case of the reference LEC down to subsecond in the case of the hybrid device. Furthermore, luminance and efficiency of the hybrid device are enhanced compared to reference LEC directly after device turn-on by a factor of 400 and 650, respectively. We attribute these improvements to an increased electron injection efficiency into the iTMC directly after device turn-on. PMID- 27557051 TI - The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. PMID- 27557050 TI - Association of Admission Laboratory Values and the Timing of Endoscopic Retrograde Cholangiopancreatography With Clinical Outcomes in Acute Cholangitis. AB - Importance: Acute cholangitis (AC), particularly severe AC, has historically required urgent endoscopic decompression, although the timing of decompression is controversial. We previously identified 2 admission risk factors for adverse outcomes in AC: total bilirubin level greater than 10 mg/dL and white blood cell count greater than 20 000 cells/uL. Objectives: To validate previously identified prognostic factors in AC, evaluate the effect of timing of endoscopic retrograde cholangiopancreatography on clinical outcomes, and compare recent experience with AC vs an historical cohort. Design, Setting, and Participants: A retrospective analysis (2008-2015) of patients with AC (validation cohort, n = 196) was conducted at 2 academic medical centers to validate predictors of adverse outcome. Timing of endoscopic retrograde cholangiopancreatography and outcome were stratified by severity using the Tokyo Guidelines for acute cholangitis diagnosis. Outcomes for the validation cohort were compared with the derivation cohort (1995-2005; n = 114). Data analysis was conducted from July 1, 2015, to September 9, 2015. Main Outcomes and Measures: Death and a composite outcome of death or organ failure. Results: The median age of patients in the derivation cohort was 54 years (interquartile range, 40-65 years) and in the validation cohort was 59 years (45-67 years). Multivariate logistic regression analysis of the validation cohort confirmed white blood cell count of more than 20 000 cells/uL (odds ratio, 3.4; 95% CI, 1.2-9.5; P = .02) and total bilirubin level of more than 10 mg/dL (odds ratio, 5.4; 95% CI, 1.8-16.4; P = .003) as independent risk factors for poor outcomes. In the validation cohort, timing of endoscopic retrograde cholangiopancreatography was not significantly different between those with and without an adverse outcome, even when stratified by AC severity (moderate: median, 0.6 hours [interquartile range (IQR), 0.5-0.9] vs 1.7 hours [IQR, 0.7-18.0] and severe: median, 10.6 hours [IQR, 1.2-35.1] vs 25.5 hours [IQR, 15.5-58.5] for those with and without adverse events, respectively). Patients in the validation cohort had a shorter hospital length of stay (median, 7 days [IQR, 4-10 days] vs 9 days [IQR, 5-16 days]) and lower rate of intensive care unit admission (26% vs 82%), despite a higher rate of severe cholangitis (n = 131 [67%] vs n = 29 [25%]). There were no significant differences in the composite outcome between the validation and derivation cohorts (22 [18.6%] vs 44 [22.4%]; P = .47). Adjusted analysis demonstrated decreased mortality in the validation cohort (odds ratio, 0.3; 95% CI, 0.1-0.7; P = .01). Conclusions and Relevance: White blood cell count greater than 20 000 cells/uL and total bilirubin level greater than 10 mg/dL are independent prognostic factors for adverse outcomes in AC. Consideration should be given to include these criteria in the Tokyo Guidelines severity assessment. Timing of endoscopic retrograde cholangiopancreatography does not appear to affect clinical outcomes in these patients. Management of AC has improved with time, with an overall shorter hospital length of stay, lower rate of intensive care unit admission, and a decreased adjusted mortality, demonstrating improvements in care efficiency and delivery. PMID- 27557052 TI - Long-Term Cost-Effectiveness of Transanal Irrigation in Patients with Neurogenic Bowel Dysfunction. AB - BACKGROUND: People suffering from neurogenic bowel dysfunction (NBD) and an ineffective bowel regimen often suffer from fecal incontinence (FI) and related symptoms, which have a huge impact on their quality of life. In these situations, transanal irrigation (TAI) has been shown to reduce these symptoms and improve quality of life. AIM: To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC). METHODS: A deterministic Markov decision model was developed to project the lifetime health economic outcomes, including quality-adjusted life years (QALYs), episodes of FI, urinary tract infections (UTIs), and stoma surgery when initiating TAI relative to continuing SBC. A data set consisting of 227 patients with NBD due to spinal cord injury (SCI), multiple sclerosis, spina bifida and cauda equina syndrome was used in the analysis. In the model a 30-year old individual with SCI was used as a base-case. A probabilistic sensitivity analysis was applied to evaluate the robustness of the model. RESULTS: The model predicts that a 30-year old SCI patient with a life expectancy of 37 years initiating TAI will experience a 36% reduction in FI episodes, a 29% reduction in UTIs, a 35% reduction in likelihood of stoma surgery and a 0.4 improvement in QALYs, compared with patients continuing SBC. A lifetime cost-saving of L21,768 per patient was estimated for TAI versus continuing SBC alone. CONCLUSION: TAI is a cost-saving treatment strategy reducing risk of stoma surgery, UTIs, episodes of FI and improving QALYs for NBD patients who have failed SBC. PMID- 27557054 TI - Evaluating Perceived Probability of Threat-Relevant Outcomes and Temporal Orientation in Flying Phobia. AB - Probability bias regarding threat-relevant outcomes has been demonstrated across anxiety disorders but has not been investigated in flying phobia. Individual temporal orientation (time perspective) may be hypothesised to influence estimates of negative outcomes occurring. The present study investigated whether probability bias could be demonstrated in flying phobia and whether probability estimates of negative flying events was predicted by time perspective. Sixty flying phobic and fifty-five non-flying-phobic adults were recruited to complete an online questionnaire. Participants completed the Flight Anxiety Scale, Probability Scale (measuring perceived probability of flying-negative events, general-negative and general positive events) and the Past-Negative, Future and Present-Hedonistic subscales of the Zimbardo Time Perspective Inventory (variables argued to predict mental travel forward and backward in time). The flying phobic group estimated the probability of flying negative and general negative events occurring as significantly higher than non-flying phobics. Past Negative scores (positively) and Present-Hedonistic scores (negatively) predicted probability estimates of flying negative events. The Future Orientation subscale did not significantly predict probability estimates. This study is the first to demonstrate probability bias for threat-relevant outcomes in flying phobia. Results suggest that time perspective may influence perceived probability of threat-relevant outcomes but the nature of this relationship remains to be determined. PMID- 27557053 TI - Molecular Components of the Neurospora crassa pH Signaling Pathway and Their Regulation by pH and the PAC-3 Transcription Factor. AB - Environmental pH induces a stress response triggering a signaling pathway whose components have been identified and characterized in several fungi. Neurospora crassa shares all six components of the Aspergillus nidulans pH signaling pathway, and we investigate here their regulation during an alkaline pH stress response. We show that the N. crassa pal mutant strains, with the exception of Deltapal-9, which is the A. nidulans palI homolog, exhibit low conidiation and are unable to grow at alkaline pH. Moreover, they accumulate the pigment melanin, most likely via regulation of the tyrosinase gene by the pH signaling components. The PAC-3 transcription factor binds to the tyrosinase promoter and negatively regulates its gene expression. PAC-3 also binds to all pal gene promoters, regulating their expression at normal growth pH and/or alkaline pH, which indicates a feedback regulation of PAC-3 in the pal gene expression. In addition, PAC-3 binds to the pac-3 promoter only at alkaline pH, most likely influencing the pac-3 expression at this pH suggesting that the activation of PAC-3 in N. crassa results from proteolytic processing and gene expression regulation by the pH signaling components. In N. crassa, PAC-3 is proteolytically processed in a single cleavage step predominately at alkaline pH; however, low levels of the processed protein can be observed at normal growth pH. We also demonstrate that PAC-3 preferentially localizes in the nucleus at alkaline pH stress and that the translocation may require the N. crassa importin-alpha since the PAC-3 nuclear localization signal (NLS) has a strong in vitro affinity with importin-alpha. The data presented here show that the pH signaling pathway in N. crassa shares all the components with the A. nidulans and S. cerevisiae pathways; however, it exhibits some properties not previously described in either organism. PMID- 27557055 TI - Synthesis of Fluorine-Doped Hydrophilic Carbon Nanoparticles from Hexafluorobenzene by Femtosecond Laser Pulses. AB - We report on the preparation and characterization of fluorine-doped hydrophilic carbon nanoparticles by the exposure of hexafluorobenzene or a water/hexafluorobenzene bilayer solution to femtosecond laser pulses. Uniform atom distributions are achieved not only on the particle surface but also inside the particles. The semi-ionic character of C-F bonds and the non-aggregating feature of the nanoparticles play key roles in the water-dispersible character of fluorine-doped carbon nanoparticles. We suggest the following building-up process of carbon nanoparticles: the fragmentation of hexafluorobenzene initiated by the electrons generated in laser-induced plasma followed by the reconstruction of a carbon framework of nanoparticles. PMID- 27557056 TI - Chemical Insight into the Mechanism and Specificity of GlfT2, a Bifunctional Galactofuranosyltransferase from Mycobacteria. AB - Mycobacteria, including the human pathogen Mycobacterium tuberculosis, produce a complex cell wall structure that is essential to survival. A key component of this structure is a glycoconjugate, the mycolyl-arabinogalactan-peptidoglycan complex, which has at its core a galactan domain composed of galactofuranose (Galf) residues linked to peptidoglycan. Because galactan biosynthesis is essential for mycobacterial viability, compounds that interfere with this process are potential therapeutic agents for treating mycobacterial diseases, including tuberculosis. Galactan biosynthesis in mycobacteria involves two glycosyltransferases, GlfT1 and GlfT2, which have been the subject of increasing interest in recent years. This Synopsis summarizes efforts to characterize the mechanism and specificity of GlfT2, which is responsible for introducing the majority of the Galf residues into mycobacterial galactan. PMID- 27557057 TI - Highly beta-Selective Cyclopolymerization of 1,6-Heptadiynes and Ring-Closing Enyne Metathesis Reaction Using Grubbs Z-Selective Catalyst: Unprecedented Regioselectivity for Ru-Based Catalysts. AB - It is well-known that Ru-based Grubbs catalysts undergo a highly selective alpha addition to alkynes to promote exo-cyclization during ring-closing enyne metathesis (RCEYM) or to produce conjugated polyenes containing five-membered rings during the cyclopolymerization (CP) of 1,6-heptadiynes. There are a few reports of beta-selective addition to alkynes using Schrock catalysts based on Mo but none for readily accessible and easy-to-use Ru-based catalysts. We report the first example of beta-selective addition to alkynes using Grubbs Z-selective catalyst, which produces only endo products during the RCEYM reaction of terminal enynes and promotes the CP of 1,6-heptadiyne derivatives to give conjugated polyenes containing a six-membered ring as a major repeat unit. This unique preference for beta-selectivity originated from the side-bound approach of alkynes to the catalyst, where the steric hindrance between the chelating N heterocyclic carbene ligand of the catalyst and the alkynes disfavored alpha addition. To enhance the beta-selectivity for CP further, one could increase the size of the substrates on the monomers and lower the reaction temperature to obtain conjugated polyenes containing up to 95% six-membered rings. Moreover, the physical properties of the resulting polymer were analyzed in detail and compared with those of the conjugated polyenes containing only five-membered rings prepared from the same monomer but with a conventional Grubbs catalyst. PMID- 27557058 TI - Considerations of the Effects of Naphthalene Moieties on the Design of Proton Conductive Poly(arylene ether ketone) Membranes for Direct Methanol Fuel Cells. AB - Novel sulfonated poly(arylene ether ketones) (SDN-PAEK-x), consisting of dual naphthalene and flexible sulfoalkyl groups, were prepared via polycondensation, demethylation, and sulfobutylation grafting reaction. Among them, SDN-PAEK-1.94 membrane with the highest ion exchange capacity (IEC = 2.46 mequiv.g(-1)) exhibited the highest proton conductivity, which was 0.147 S. cm(-1) at 25 degrees C and 0.271 S.cm(-1) at 80 degrees C, respectively. The introduction of dual naphthalene moieties is expected to achieve much enhanced properties compared to those of sulfonated poly(arylene ether ketones) (SNPAEK-x), consisting of single naphthalene and flexible sulfoalkyl groups. Compared with SNPAEK-1.60 with a similar IEC, SDN-PAEK-1.74 membrane showed higher proton conductivity, higher IEC normalized conductivity, and higher effective proton mobility, although it had lower analytical acid concentration. The SDN-PAEK-x membranes with IECs higher than 1.96 mequiv.g(-1) also exhibited higher proton conductivity than that of recast Nafion membrane. Furthermore, SDN-PAEK-1.94 displayed a better single cell performance with a maximum power density of 60 mW.cm(-2) at 80 degrees C. Considering its high proton conductivity, excellent single cell performance, good mechanical stabilities, low membrane swelling, and methanol permeability, SDN-PAEK-x membranes are promising candidates as alternative polymer electrolyte membranes to Nafion for direct methanol fuel cell applications. PMID- 27557059 TI - [Anaemia in the elderly - calculation of iron requirement]. PMID- 27557060 TI - [Anaemia in the elderly: calculation of iron requirement - in reply]. PMID- 27557061 TI - [Is Pioglitazone blessing or curse?]. PMID- 27557062 TI - [Statins potentially improve prognosis of Prinzmetal's angina patients]. PMID- 27557063 TI - [Regular ASA intake is associated with lower risk for cancer]. PMID- 27557064 TI - [Not Available]. PMID- 27557065 TI - [28-year old woman with sore throat, fever and haemogram changes]. PMID- 27557066 TI - [Not Available]. PMID- 27557067 TI - [Cognitive dysfunction in cardiovascular diseases]. AB - A multitude of modifiable risk factors during the median phase of life are often causative for cognitive dysfunction (CD) in old age. High evidence exists for cigarette smoking, diabetes, physical inactivity and sleeping disorders. Single large scale population based studies proof it for hypertension, hypercholesterinemia and depression, conflicting evidence exists for obesity and work stress. Little attention is paid to the close association between cardiovascular disease conditions and CD, particularly for atrial fibrillation, heart failure and for older patients with coronary heart disease. Undetected CD may be responsible for non-adherence and failure of self-care programs in chronic heart patients. PMID- 27557068 TI - [Depression and heart failure - a dangerous combination]. AB - Depression is common in heart failure and associated with impaired quality of life. It impacts adversely on clinical outcomes. Both diseases are widespread in the general population with increasing prevalence and treatment costs. They are therefore also of socio-economic relevance. Various interrelated biological and behavioral factors (e.g. lower treatment adherence in depressed patients with heart failure) seem to play a pathophysiological role, and there is growing evidence that both diseases may also share genetic susceptibilities. Simple screening tools ease depression diagnosis in clinical practice, although the clinical profile of both disorders overlaps. To date, there is no evidence that antidepressant pharmacotherapy improves depressive symptoms, mortality and morbidity in patients with heart failure and comorbid depression, but physical training, cognitive behavioral therapy and comprehensive disease management improved symptoms and/or prognosis in individual randomized studies. PMID- 27557069 TI - [Anxiety in progressive disease]. AB - Anxiety in terminally ill patients has a high impact on symptoms, trajectory and quality of life. There are different screening instruments for diagnosis. The holistic approach of palliative care considers the physical, psychological, social and spiritual needs and can improve the distress caused by anxiety. Early integration in palliative care decreases burden of symptoms and increases quality of life. PMID- 27557070 TI - [Bronchoscopy]. AB - Bronchoscopy is a diagnostic method of examination of the airways and the lung parenchyma, which can be performed in rigid or flexible examination technique. It is used for early detection and diagnosis of pulmonary diseases. Depending on the indication can be performed bronchial tumor biopsy, microbiological rinse, brush biopsy for cytology or microbiology, bronchoalveolar lavage (BAL) for differential and Immunocytology or needle biopsy for cytology. After each measure should be excluded after a hemorrhage and pneumothorax especially after transbronchial biopsy. PMID- 27557071 TI - [Neuralgic amyotrophy: an extrahepatic manifestation of hepatitis E]. AB - History and initial findings | A patient with bilateral pain in his shoulders is presented at the emergency room. Investigations | There were strongly increased transaminases. Diagnosis | Serology and PCR led to the diagnosis of hepatitis E. Neurological examination revealed a neuralgic amyotrophy Treatment and course | The pain in the shoulders disappeared spontaneously after vanishing of HEV viremia. Conclusion | Patients with shoulder pain of unknown origin and elevated transaminases should be tested for hepatitis E. PMID- 27557072 TI - [Patient from Gambia with sonographic white kidneys]. AB - HISTORY AND ADMISSION FINDINGS: A 39-year-old male refugee from Gambia is admitted to the emergency room with fever, body aches and productive cough. INVESTIGATIONS: Laboratory, ultrasound and CT investigations show a sepsis due to Staphylcoccus aureus, a renal failure with the appearance of "snow-white" kidneys on ultrasound and a previously unknown acute HIV-infection. DIAGNOSIS, TREATMENT AND COURSE: Broad antibiotic treatment and an antiretroviral therapy (adapted to the impaired renal function) as well as hemodialysis are commenced. Despite of successful sepsis treatment and viral load reduction, the kidney function does not recover. Histologically, a HIV-nephropathy is confirmed. CONCLUSIONS: The appearance of "snow-white" kidneys on ultrasound can be a characteristic sign of a HIV-associated nephropathy. PMID- 27557073 TI - [Autoimmune encephalitis]. AB - Autoimmune encephalitis, an inflammatory disease of the brain, is usually attributed to antibody-mediated damage and dysfunction of neuronal structures. A distinction is made between onconeuronal antibodies (directed against intracellular neuronal antigens with resulting paraneoplastic neurological syndromes) and antibodies directed against neuronal cell surface proteins (with resulting synaptic encephalopathies). Anti-NMDA-Receptor-Encephalitis, the most common form of autoimmune encephalopathy, is characterized by a phased course of disease. Early disease phase involves nonspecific prodromes (fatigue, fever, headache) which lead to family doctor or emergency department consultation. Subsequently, neuropsychiatric behavioural problems, seizures, disturbance of memory and finally coma, dysautonomia and respiratory insufficiency often result in major complications (e.g. status epilepticus) necessitating intensive care treatment. The diagnosis is secured by detection of auto-antibodies in serum or cerebrospinal fluid. An intensive search for tumors is also recommended. The treatment of autoimmune encephalitis comprises of immunomodulatory and immunosuppessive strategies. Tumor therapy is the most important treatment of autoimmune encephalitis by onconeuronal antibodies. PMID- 27557074 TI - [Incontinence - Etiology, diagnostics and Therapy]. AB - Fecal incontinence is defined by the unintentional loss of solid or liquid stool, and anal incontinence includes leakage of gas and / or fecal incontinence. Anal fecal incontinence is not a diagnosis but a symptom. Many patients hide the problem from their families, friends, and even their doctors. Epidemiologic studies indicate a prevalence between 7-15 %, up to 30 % in hospitals and up to 70 % in longterm care settings. Anal-fecal incontinence causes a significant socio-economic burden. There is no widely accepted approach for classifying anal fecal incontinence available. Anal-fecal continence is maintained by anatomical factors, rectoanal sensation, and rectal compliance. The diagnostic approach comprises muscle and nerve injuries by iatrogenic, obstetric or surgical trauma, descending pelvic floor or associated diseases. A basic diagnostic workup is sufficient to characterize the different manifestations of fecal incontinence in most of the cases. This includes patient history with a daily stool protocol and digital rectal investigation. Additional investigations may include anorectal manometry, anal sphincter EMG, conduction velocity of the pudendal nerve, needle EMG, barostat investigation, defecography and the dynamic MRI. Therapeutic interventions are focused on the individual symptoms and should be provided in close cooperation with gastroenterologists, surgeons, gynecologists, urologists, physiotherapeutics and psychologists (nutritional-training, food fibre content, pharmacological treatment of diarrhea/constipation, toilet training, pelvic floor gymnastic, anal sphincter training, biofeedback). Surgical therapy includes the STARR operation for rectoanal prolapse and sacral nerve stimulation for chronic constipation and anal-fecal incontinence. Surgery should not be applied unless the diagnostic work-up is complete and all conservative treatment options failed. PMID- 27557075 TI - [Epidemiological study on place of death for cancer patients Autoren]. AB - Background | In Germany, place of death is recorded on death certificates, but is not analyzed further. In consequence, only little is known about the place of death among cancer patients at the population level. The aim of the study was to describe the changes of places of death in cancer patients over a time period of 10 years. Material and methods | This study examined death certificates from 2001 and 2011 of selected regions of Westphalia-Lippe (Germany). Cancer patients were identified on the basis of cause of death. Description of frequencies of place of death and subgroup analyses by tumor entity (ICD-10, C00-C96) were performed. Results | A total of 24 009 death certificates were analyzed (2001: 11,585; 2011: 12,424). Cancer was the underlying or contributory cause of death in 34.0%. For the years 2001 and 2011, respectively, the following distributions of place of death were observed: home, 24.1% vs. 24.7% (p=0.553); hospital, 62.8% vs. 51.4% (p=0.001); palliative care unit, 0.0% vs. 2.2%; hospice, 5.5% vs. 12.5% (p=0.001); nursing home, 7.4% vs. 10.9% (p=0.001); other, 0.1% vs. 0.3% (p=0.063); no data, 0.1% vs. 0.3% (p=0.015). Patients with brain tumours had a higher probability of dying in a hospice (2011: female 23.5%; male 27.7%). A higher risk of death in hospital was observed among cancer patients with an underlying hematological malignancy (2011: female 63.7%; male 68.4%). Conclusion | Cancer patients mainly die in institutions, with hospitals being the most frequent location. Only one in four deaths occurs in the home setting. The trend over time shows a shift in place of death away from hospitals towards hospices, palliative care units, and nursing homes. PMID- 27557076 TI - A method for identifying discriminative isoform-specific peptides for clinical proteomics application. AB - BACKGROUND: Clinical proteomics application aims at solving a specific clinical problem within the context of a clinical study. It has been growing rapidly in the field of biomarker discovery, especially in the area of cancer diagnostics. Until recently, protein isoform has not been viewed as a new class of early diagnostic biomarkers for clinical proteomics. A protein isoform is one of different forms of the same protein. Different forms of a protein may be produced from single-nucleotide polymorphisms (SNPs), alternative splicing, or post translational modifications (PTMs). Previous studies have shown that protein isoforms play critical roles in tumorigenesis, disease diagnosis, and prognosis. Identifying and characterizing protein isoforms are essential to the study of molecular mechanisms and early detection of complex diseases such as breast cancer. However, there are limitations with traditional methods such as EST sequencing, Microarray profiling (exon array, Exon-exon junction array), mRNA next-generation sequencing used for protein isoform determination: 1) not in the protein level, 2) no connectivity about connection of nonadjacent exons, 3) no SNPs and PTMs, and 4) low reproducibility. Moreover, there exist the computational challenges of clinical proteomics studies: 1) low sensitivity of instruments, 2) high data noise, and 3) high variability and low repeatability, although recent advances in clinical proteomics technology, LC-MS/MS proteomics, have been used to identify candidate molecular biomarkers in diverse range of samples, including cells, tissues, serum/plasma, and other types of body fluids. RESULTS: Therefore, in the paper, we presented a peptidomics method for identifying cancer-related and isoform-specific peptide for clinical proteomics application from LC-MS/MS. First, we built a Peptidomic Database of Human Protein Isoforms, then created a peptidomics approach to perform large-scale screen of breast cancer-associated alternative splicing isoform markers in clinical proteomics, and lastly performed four kinds of validations: biological validation (explainable index), exon array, statistical validation of independent samples, and extensive pathway analysis. CONCLUSIONS: Our results showed that alternative splicing isoform makers can act as independent markers of breast cancer and that the method for identifying cancer-specific protein isoform biomarkers from clinical proteomics application is an effective one for increasing the number of identified alternative splicing isoform markers in clinical proteomics. PMID- 27557077 TI - MELODI comments on the new findings on cancer risk associated with low dose chronic radiation exposure from the INWORKS study. PMID- 27557079 TI - Effect of Cellulases and Xylanases on Refining Process and Kraft Pulp Properties. AB - Samples of bleached kraft pine cellulosic pulp, either treated with an enzyme preparation (a Thermomyces lanuginosus xylanase, an Aspergillus sp. cellulase, and a multienzyme preparation NS-22086 containing both these activities) or untreated, were refined in a laboratory PFI mill. The treatment with cellulases contained in the last two preparations significantly improved the pulp's susceptibility to refining (the target freeness value of 30 degrees SR was achieved in a significantly shorter time), increased water retention value (WRV) and fines contents while the weighted average fiber length was significantly reduced. These changes of pulp parameters caused deterioration of paper strength properties. The treatment with the xylanase, which partially hydrolyzed xylan, small amounts of which are associated with cellulose fibers, only slightly loosened the structure of fibers. These subtle changes positively affected the susceptibility of the pulp to refining (refining energy was significantly reduced) and improved the static strength properties of paper. Thus, the treatment of kraft pulps with xylanases may lead to substantial savings of refining energy without negative effects on paper characteristics. PMID- 27557078 TI - Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells. AB - BACKGROUND: Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. RESULTS: In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs. LPS-treated samples, revealing 197 exons whose BMSC splicing patterns were altered by LPS. Functional analysis of these alternatively spliced genes demonstrated significant enrichment of phosphoproteins, zinc finger proteins, and proteins undergoing acetylation. Additional bioinformatics analysis strongly suggest that LPS-induced alternatively spliced exons could have major effects on protein functions by disrupting key protein functional domains, protein-protein interactions, and post translational modifications. CONCLUSION: Although it is still to be determined whether such proteome modifications improve BMSC therapeutic efficacy, our comprehensive splicing characterizations provide greater understanding of the intracellular mechanisms that underlie the therapeutic potential of BMSCs. PMID- 27557080 TI - Development and Validation of the Bicultural Youth Acculturation Questionnaire. AB - OBJECTIVES: Acculturation is a multidimensional process involving changes in behaviour and beliefs. Questionnaires developed to measure acculturation are typically designed for specific ethnic populations and adult experiences. This study developed a questionnaire that measures acculturation among ethnically diverse populations of youth that can be included as a module in population surveys. METHODS: Questionnaires measuring acculturation in youth were identified in the literature. The importance of items from the existing questionnaires was determined using a Delphi process and this informed the development of our questionnaire. The questionnaire was then pilot tested using a sample of 248 Canadians aged 18-25 via an online system. Participants identified as East and South East Asian (27.8%), South Asian (17.7%) and Black (13.7%). The majority were 1st (33.5%) or 2nd generation immigrants (52.0%). After redundant items were eliminated, exploratory factor analysis grouped items into domains, and, for each domain, internal consistency, and convergent validity with immigrant generation then age at immigration estimated. A subset of participants re-completed the questionnaire for reliability estimation. RESULTS: The literature review yielded 117 articles that used 13 questionnaires with a total of 440 questions. The Delphi process reduced these to 32 questions. Pilot testing occurred in 248 Canadians aged 18-25. Following item reduction, 16 questions in three domains remained: dominant culture, heritage language, and heritage culture. All had good internal consistency (Cronbach's alphas > .75). The mean dominant domain score increased with immigrant generation (1st generation: 3.69 (95% CI: 3.49-3.89), 2nd: 4.13 (4.00-4.26), 3rd: 4.40 (4.19-4.61)), and mean heritage language score was higher among those who immigrated after age 12 than before (p = .0001), indicative of convergent validity. CONCLUSIONS: This Bicultural Youth Acculturation Questionnaire has demonstrated validity. It can be incorporated into population health surveys to elucidate the impact of acculturation on health outcomes among bicultural youth. PMID- 27557081 TI - Correction: Human Rabies Survivors in India: An Emerging Paradox? AB - [This corrects the article DOI: 10.1371/journal.pntd.0004774.]. PMID- 27557082 TI - Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 Is Not Required for Gene Regulation or Virulence. AB - The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a DeltapstA1DeltapstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, DeltapstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a DeltapstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions. PMID- 27557083 TI - FEATURES OF POSTERIOR STAPHYLOMAS ANALYZED IN WIDE-FIELD FUNDUS IMAGES IN PATIENTS WITH UNILATERAL AND BILATERAL PATHOLOGIC MYOPIA. AB - PURPOSE: Pigmentary alterations along the presumed edge of staphyloma in wide field fundus images have been reported to be highly correlated with the eye shape in three-dimensional magnetic resonance images. The purpose of this study was to analyze Optos images in a large series of highly myopic patients to determine the prevalence, types, and features of staphylomas. METHODS: One thousand and sixty eyes of 541 patients with high myopia (axial length >= 26.5 mm) in at least one eye were retrospectively analyzed in Japan and Spain. To determine the presence and types of staphyloma, the authors focused on pigmentary abnormalities along the presumed edge of staphylomas with at least one positive finding in fundus images, autofluorescent images, and infrared images by Optos. RESULTS: Posterior staphyloma was detected in 552 of 1,060 eyes (55%) in Optos images. Wide macular type was the most common (79%), followed by narrow macular (15%), then peripapillary (3%), inferior, and finally nasal. In the 60 non-highly myopic eyes of patients with unilateral high myopia, staphyloma was detected in 40%, suggesting that unilateral high myopia might be a bilateral disorder with marked differences in the degree of staphyloma between the two eyes. Combined staphylomas such as the peripapillary type within the wide macular type were also found. CONCLUSION: Posterior staphyloma was found in 55% of 1,060 eyes with bilateral or unilateral pathologic myopia. Wide macular was the most common type, although there were much more variations in the shape of staphylomas than that had been previously believed. PMID- 27557085 TI - LONGITUDINAL QUANTITATIVE EVALUATION OF OUTER RETINAL LESIONS IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY USING OPTICAL COHERENCE TOMOGRAPHY. AB - PURPOSE: To quantify the external limiting membrane (ELM) disruption and photoreceptor volume changes in eyes with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using Spectral Domain Optical Coherence Tomography (SD-OCT) at the acute and resolution phases. METHODS: Retrospective study of 10 eyes of 5 patients with APMPPE. Intact ELM and the Bruch's membrane were manually traced using ImageJ software and their lengths from each scan of the Spectral Domain Optical Coherence Tomography macular volume were summed. The ratio of intact ELM length/Bruch's membrane length was calculated. Also, two dimensional areas of specific regions of interest were demarcated between the intact ELM and Bruch's Membrane in every cross-sectional B-scan. Total volume of photoreceptors was calculated by multiplying the total area by the distance between B-scans. RESULTS: There was a statistically significant increase in ELM/Bruch's membrane ratio (P value = 0.022), mean photoreceptors volume (P value = 0.028), and a significant linear positive correlation between change of intact ELM/Bruch's membrane ratio and percent change of photoreceptor volume (r = 0.927, P value = 0.001) when comparing baseline and final follow-up visit, independent of total follow-up length. CONCLUSION: Using Spectral Domain-Optical Coherence Tomography, we showed that quantitative evaluation of ELM disruption and the volume of photoreceptor recovery can help us to follow the clinical course of APMPPE. PMID- 27557084 TI - ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY. AB - PURPOSE: To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. METHODS: The study was prospective and cross-sectional. A 1,050 nm wavelength, 400 kHz A-scan rate swept source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. RESULTS: Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. CONCLUSION: The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes. PMID- 27557086 TI - CHANGES IN CHOROIDAL THICKNESS IN AND OUTSIDE THE MACULA AFTER HEMODIALYSIS IN PATIENTS WITH END-STAGE RENAL DISEASE. AB - PURPOSE: To evaluate changes in choroidal thickness in and outside the macula as a result of hemodialysis (HD) in patients with end-stage renal disease. METHODS: Patients with end-stage renal disease treated with maintenance HD in the Dialysis Unit of Sanggye Paik Hospital, Seoul, South Korea, were included in this study. The choroidal thickness was measured in and outside the macula before and after HD (paired t-test). Choroidal thickness in the macula was measured at the foveal center and 1.5 mm temporal to the foveal center and outside the macula was measured at superior, inferior, and nasal area 3.5 mm from the optic disk margin. Peripapillary retinal nerve fiber layer thickness, intraocular pressure, central corneal thickness, and systemic parameters such as serum osmolarity and blood pressure (BP) were measured before and after HD (paired t-test). We divided patients into two groups, diabetic and nondiabetic groups to compare the changes in choroidal thickness. Patients with diabetes were subdivided into two groups: severe retinal change group and moderate retinal change group (Mann-Whitney test). Pearson's correlation test was used to evaluate the correlations between choroidal thickness and changes in serum osmolarity, BP, and body weight loss. Choroidal thickness and peripapillary retinal nerve fiber layer thickness were measured using spectral-domain optical coherence tomography. RESULTS: Fifty-four eyes of 31 patients with end-stage renal disease were included. After HD, the mean intraocular pressure was significantly decreased from 14.8 +/- 2.5 mmHg to 13.0 +/- 2.6 mmHg (P < 0.001). Choroidal thickness was reduced in all areas (P < 0.001). The reduction in choroidal thickness correlated with body weight loss, decrease in serum osmolarity, and decrease in systolic BP (P < 0.05). In the diabetic group, the mean choroidal thickness changes were greater than those in the nondiabetic group (P < 0.05). The severe retinal change group showed greater changes in choroidal thickness in all areas (P < 0.05). Other factors that significantly decreased after HD included serum osmolarity, body weight, and systolic BP (all P < 0.001). The diabetic group showed greater changes in serum osmolarity and body weight (P < 0.001, P = 0.048, respectively). The measured overall changes in peripapillary retinal nerve fiber layer thickness or central corneal thickness were not statistically significant. CONCLUSION: Changes in body weight, serum osmolarity, and BP during HD may affect choroidal thickness in and outside the macula. PMID- 27557088 TI - Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships. AB - BACKGROUND: Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. OBJECTIVES: Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. METHODS: A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. RESULTS: A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). CONCLUSION: Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes. PMID- 27557089 TI - Facile Peeling Method as a Post-Remedy Strategy for Producing an Ultrasmooth Self Assembled Monolayer for High-Performance Organic Transistors. AB - The modification of dielectric surface with a self-assembled monolayer (SAM) such as octadecyltrichlorosilane (OTS) is a widely used method to tune the electrical property of diverse electronic devices based on organic semiconductors, graphene, transition metal dichalcogenides (TMDs), and so forth. The surface roughness of self-assembled OTS monolayer is a key factor in determining its effect on device performance, but the preparation of an ultrasmooth OTS monolayer is a technologically challenging task. In this work, an ultrasmooth OTS monolayer is prepared via a facile peeling method, which may serve as a postremedy strategy to remove the protuberant aggregates. Such a method has not been reported before. With organic semiconductors as a testing model, ultrasmooth OTS may significantly improve the charge mobility of organic field-effect transistors (OFETs). P-type dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) OFET with an ultrasmooth OTS monolayer yields good reproducibility and unprecendented maximum mobility of 8.16 cm(2) V(-1) s(-1), which is remarkably superior to that of the OFET with a pristine OTS monolayer. This work develops a simple method to resolve the common and significant problem of the quality of OTS modification, which would be highly promising for electronic applications as well as other fields such as surface and interface engineering. PMID- 27557090 TI - Effect of Drug Interactions and Adherence to Warfarin Therapy on Patients-Reply. PMID- 27557091 TI - Structure and properties of iron oxide clusters: From Fe6 to Fe6 O20 and from Fe7 to Fe7 O24. AB - Geometrical and electronic structures of the neutral and singly negatively charged Fe6 On and Fe7 Om clusters in the range of 1 <= n <= 20 and 1 <= m <= 24, respectively, are computed using density functional theory with the generalized gradient approximation. The largest clusters in the two series, Fe6 O20 and Fe7 O24 , can be described as Fe(FeO4 )5 and Fe(FeO4 )6 or alternatively as [FeO5 ](FeO3 )5 and [FeO6 ](FeO3 )6 , respectively. The Fe6 O20 and Fe7 O24 clusters possess adiabatic electron affinities (EAad ) of 5.64 eV and 5.80 eV and can be attributed to the class of hyperhalogens since FeO4 is an unique closed-shell superhalogen with the EAad of 3.9 eV. The spin character of the lowest total energy states in both series changes from ferromagnetic to ferrimagnetic or antiferromagnetic when the first Fe?O?Fe bridge is formed. Oxidation decreases substantially the polarizability per atom of the initial bare clusters; namely, from 5.98 A(3) of Fe6 to 2.47 A(3) of Fe6 O20 and from 5.67 A(3) of Fe7 to 2.38 A(3) of Fe7 O24 . The results of our computations pertaining to the binding energies of O, Fe, O2 , and FeO in the Fe7 Om series provide an explanation for the experimentally observed abundance of the iron oxide nanoparticles with stoichiometric compositions. (c) 2016 Wiley Periodicals, Inc. PMID- 27557093 TI - Climate Change and Future Pollen Allergy in Europe. AB - BACKGROUND: Globally, pollen allergy is a major public health problem, but a fundamental unknown is the likely impact of climate change. To our knowledge, this is the first study to quantify the consequences of climate change upon pollen allergy in humans. OBJECTIVES: We produced quantitative estimates of the potential impact of climate change upon pollen allergy in humans, focusing upon common ragweed (Ambrosia artemisiifolia) in Europe. METHODS: A process-based model estimated the change in ragweed's range under climate change. A second model simulated current and future ragweed pollen levels. These findings were translated into health burdens using a dose-response curve generated from a systematic review and from current and future population data. Models considered two different suites of regional climate/pollen models, two greenhouse gas emissions scenarios [Representative Concentration Pathways (RCPs) 4.5 and 8.5], and three different plant invasion scenarios. RESULTS: Our primary estimates indicated that sensitization to ragweed will more than double in Europe, from 33 to 77 million people, by 2041-2060. According to our projections, sensitization will increase in countries with an existing ragweed problem (e.g., Hungary, the Balkans), but the greatest proportional increases will occur where sensitization is uncommon (e.g., Germany, Poland, France). Higher pollen concentrations and a longer pollen season may also increase the severity of symptoms. Our model projections were driven predominantly by changes in climate (66%) but were also influenced by current trends in the spread of this invasive plant species. Assumptions about the rate at which ragweed spreads throughout Europe had a large influence upon the results. CONCLUSIONS: Our quantitative estimates indicate that ragweed pollen allergy will become a common health problem across Europe, expanding into areas where it is currently uncommon. Control of ragweed spread may be an important adaptation strategy in response to climate change. Citation: Lake IR, Jones NR, Agnew M, Goodess CM, Giorgi F, Hamaoui-Laguel L, Semenov MA, Solomon F, Storkey J, Vautard R, Epstein MM. 2017. Climate change and future pollen allergy in Europe. Environ Health Perspect 125:385-391; http://dx.doi.org/10.1289/EHP173. PMID- 27557094 TI - Delta9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats. AB - BACKGROUND: Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug induced cognitive impairments. Delta9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. METHODS: Male Long-Evans rats (n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. RESULTS: We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats. LIMITATIONS: Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. CONCLUSION: These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction. PMID- 27557095 TI - Correction: Kinomic Profiling of Electromagnetic Navigational Bronchoscopy Specimens: A New Approach for Personalized Medicine. AB - [This corrects the article DOI: 10.1371/journal.pone.0116388.]. PMID- 27557096 TI - Innovative Visualizations Shed Light on Avian Nocturnal Migration. AB - Globally, billions of flying animals undergo seasonal migrations, many of which occur at night. The temporal and spatial scales at which migrations occur and our inability to directly observe these nocturnal movements makes monitoring and characterizing this critical period in migratory animals' life cycles difficult. Remote sensing, therefore, has played an important role in our understanding of large-scale nocturnal bird migrations. Weather surveillance radar networks in Europe and North America have great potential for long-term low-cost monitoring of bird migration at scales that have previously been impossible to achieve. Such long-term monitoring, however, poses a number of challenges for the ornithological and ecological communities: how does one take advantage of this vast data resource, integrate information across multiple sensors and large spatial and temporal scales, and visually represent the data for interpretation and dissemination, considering the dynamic nature of migration? We assembled an interdisciplinary team of ecologists, meteorologists, computer scientists, and graphic designers to develop two different flow visualizations, which are interactive and open source, in order to create novel representations of broad front nocturnal bird migration to address a primary impediment to long-term, large-scale nocturnal migration monitoring. We have applied these visualization techniques to mass bird migration events recorded by two different weather surveillance radar networks covering regions in Europe and North America. These applications show the flexibility and portability of such an approach. The visualizations provide an intuitive representation of the scale and dynamics of these complex systems, are easily accessible for a broad interest group, and are biologically insightful. Additionally, they facilitate fundamental ecological research, conservation, mitigation of human-wildlife conflicts, improvement of meteorological products, and public outreach, education, and engagement. PMID- 27557098 TI - Presynaptic Spontaneous Activity Enhances the Accuracy of Latency Coding. AB - The time to the first spike after stimulus onset typically varies with the stimulation intensity. Experimental evidence suggests that neural systems use such response latency to encode information about the stimulus. We investigate the decoding accuracy of the latency code in relation to the level of noise in the form of presynaptic spontaneous activity. Paradoxically, the optimal performance is achieved at a nonzero level of noise and suprathreshold stimulus intensities. We argue that this phenomenon results from the influence of the spontaneous activity on the stabilization of the membrane potential in the absence of stimulation. The reported decoding accuracy improvement represents a novel manifestation of the noise-aided signal enhancement. PMID- 27557097 TI - Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage. AB - Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID- 27557099 TI - The Space-Clamped Hodgkin-Huxley System with Random Synaptic Input: Inhibition of Spiking by Weak Noise and Analysis with Moment Equations. AB - We consider a classical space-clamped Hodgkin-Huxley model neuron stimulated by synaptic excitation and inhibition with conductances represented by Ornstein Uhlenbeck processes. Using numerical solutions of the stochastic model system obtained by an Euler method, it is found that with excitation only, there is a critical value of the steady-state excitatory conductance for repetitive spiking without noise, and for values of the conductance near the critical value, small noise has a powerfully inhibitory effect. For a given level of inhibition, there is also a critical value of the steady-state excitatory conductance for repetitive firing, and it is demonstrated that noise in either the excitatory or inhibitory processes or both can powerfully inhibit spiking. Furthermore, near the critical value, inverse stochastic resonance was observed when noise was present only in the inhibitory input process. The system of deterministic differential equations for the approximate first- and second-order moments of the model is derived. They are solved using Runge-Kutta methods, and the solutions are compared with the results obtained by simulation for various sets of parameters, including some with conductances obtained by experiment on pyramidal cells of rat prefrontal cortex. The mean and variance obtained from simulation are in good agreement when there is spiking induced by strong stimulation and relatively small noise or when the voltage is fluctuating at subthreshold levels. In the occasional spike mode sometimes exhibited by spinal motoneurons and cortical pyramidal cells, the assumptions underlying the moment equation approach are not satisfied. The simulation results show that noisy synaptic input of either an excitatory or inhibitory character or both may lead to the suppression of firing in neurons operating near a critical point and this has possible implications for cortical networks. Although suppression of firing is corroborated for the system of moment equations, there seem to be substantial differences between the dynamical properties of the original system of stochastic differential equations and the much larger system of moment equations. PMID- 27557100 TI - Energy-Efficient Neuromorphic Classifiers. AB - Neuromorphic engineering combines the architectural and computational principles of systems neuroscience with semiconductor electronics, with the aim of building efficient and compact devices that mimic the synaptic and neural machinery of the brain. The energy consumptions promised by neuromorphic engineering are extremely low, comparable to those of the nervous system. Until now, however, the neuromorphic approach has been restricted to relatively simple circuits and specialized functions, thereby obfuscating a direct comparison of their energy consumption to that used by conventional von Neumann digital machines solving real-world tasks. Here we show that a recent technology developed by IBM can be leveraged to realize neuromorphic circuits that operate as classifiers of complex real-world stimuli. Specifically, we provide a set of general prescriptions to enable the practical implementation of neural architectures that compete with state-of-the-art classifiers. We also show that the energy consumption of these architectures, realized on the IBM chip, is typically two or more orders of magnitude lower than that of conventional digital machines implementing classifiers with comparable performance. Moreover, the spike-based dynamics display a trade-off between integration time and accuracy, which naturally translates into algorithms that can be flexibly deployed for either fast and approximate classifications, or more accurate classifications at the mere expense of longer running times and higher energy costs. This work finally proves that the neuromorphic approach can be efficiently used in real-world applications and has significant advantages over conventional digital devices when energy consumption is considered. PMID- 27557101 TI - Identification of Stable Spike-Timing-Dependent Plasticity from Spiking Activity with Generalized Multilinear Modeling. AB - Characterization of long-term activity-dependent plasticity from behaviorally driven spiking activity is important for understanding the underlying mechanisms of learning and memory. In this letter, we present a computational framework for quantifying spike-timing-dependent plasticity (STDP) during behavior by identifying a functional plasticity rule solely from spiking activity. First, we formulate a flexible point-process spiking neuron model structure with STDP, which includes functions that characterize the stationary and plastic properties of the neuron. The STDP model includes a novel function for prolonged plasticity induction, as well as a more typical function for synaptic weight change based on the relative timing of input-output spike pairs. Consideration for system stability is incorporated with weight-dependent synaptic modification. Next, we formalize an estimation technique using a generalized multilinear model (GMLM) structure with basis function expansion. The weight-dependent synaptic modification adds a nonlinearity to the model, which is addressed with an iterative unconstrained optimization approach. Finally, we demonstrate successful model estimation on simulated spiking data and show that all model functions can be estimated accurately with this method across a variety of simulation parameters, such as number of inputs, output firing rate, input firing type, and simulation time. Since this approach requires only naturally generated spikes, it can be readily applied to behaving animal studies to characterize the underlying mechanisms of learning and memory. PMID- 27557102 TI - On the Analytical Solution of Firing Time for SpikeProp. AB - Error backpropagation in networks of spiking neurons (SpikeProp) shows promise for the supervised learning of temporal patterns. However, its widespread use is hindered by its computational load and occasional convergence failures. In this letter, we show that the neuronal firing time equation at the core of SpikeProp can be solved analytically using the Lambert W function, offering a marked reduction in execution time over the step-based method used in the literature. Applying this analytical method to SpikeProp, we find that training time per epoch can be reduced by 12% to 56% under different experimental conditions. Finally, this work opens the way for further investigations of SpikeProp's convergence behavior. PMID- 27557103 TI - Integrator or Coincidence Detector: A Novel Measure Based on the Discrete Reverse Correlation to Determine a Neuron's Operational Mode. AB - In this letter, we propose a definition of the operational mode of a neuron, that is, whether a neuron integrates over its input or detects coincidences. We complete the range of possible operational modes by a new mode we call gap detection, which means that a neuron responds to gaps in its stimulus. We propose a measure consisting of two scalar values, both ranging from -1 to +1: the neural drive, which indicates whether its stimulus excites the neuron, serves as background noise, or inhibits it; the neural mode, which indicates whether the neuron's response is the result of integration over its input, of coincidence detection, or of gap detection; with all three modes possible for all neural drive values. This is a pure spike-based measure and can be applied to measure the influence of either all or subset of a neuron's stimulus. We derive the measure by decomposing the reverse correlation, test it in several artificial and biological settings, and compare it to other measures, finding little or no correlation between them. We relate the results of the measure to neural parameters and investigate the effect of time delay during spike generation. Our results suggest that a neuron can use several different modes simultaneously on different subsets of its stimulus to enable it to respond to its stimulus in a complex manner. PMID- 27557104 TI - Simulation Neurotechnologies for Advancing Brain Research: Parallelizing Large Networks in NEURON. AB - Large multiscale neuronal network simulations are of increasing value as more big data are gathered about brain wiring and organization under the auspices of a current major research initiative, such as Brain Research through Advancing Innovative Neurotechnologies. The development of these models requires new simulation technologies. We describe here the current use of the NEURON simulator with message passing interface (MPI) for simulation in the domain of moderately large networks on commonly available high-performance computers (HPCs). We discuss the basic layout of such simulations, including the methods of simulation setup, the run-time spike-passing paradigm, and postsimulation data storage and data management approaches. Using the Neuroscience Gateway, a portal for computational neuroscience that provides access to large HPCs, we benchmark simulations of neuronal networks of different sizes (500-100,000 cells), and using different numbers of nodes (1-256). We compare three types of networks, composed of either Izhikevich integrate-and-fire neurons (I&F), single compartment Hodgkin-Huxley (HH) cells, or a hybrid network with half of each. Results show simulation run time increased approximately linearly with network size and decreased almost linearly with the number of nodes. Networks with I&F neurons were faster than HH networks, although differences were small since all tested cells were point neurons with a single compartment. PMID- 27557105 TI - The Functional Segregation and Integration Model: Mixture Model Representations of Consistent and Variable Group-Level Connectivity in fMRI. AB - The brain consists of specialized cortical regions that exchange information between each other, reflecting a combination of segregated (local) and integrated (distributed) processes that define brain function. Functional magnetic resonance imaging (fMRI) is widely used to characterize these functional relationships, although it is an ongoing challenge to develop robust, interpretable models for high-dimensional fMRI data. Gaussian mixture models (GMMs) are a powerful tool for parcellating the brain, based on the similarity of voxel time series. However, conventional GMMs have limited parametric flexibility: they only estimate segregated structure and do not model interregional functional connectivity, nor do they account for network variability across voxels or between subjects. To address these issues, this letter develops the functional segregation and integration model (FSIM). This extension of the GMM framework simultaneously estimates spatial clustering and the most consistent group functional connectivity structure. It also explicitly models network variability, based on voxel- and subject-specific network scaling profiles. We compared the FSIM to standard GMM in a predictive cross-validation framework and examined the importance of different model parameters, using both simulated and experimental resting-state data. The reliability of parcellations is not significantly altered by flexibility of the FSIM, whereas voxel- and subject-specific network scaling profiles significantly improve the ability to predict functional connectivity in independent test data. Moreover, the FSIM provides a set of interpretable parameters to characterize both consistent and variable aspects functional connectivity structure. As an example of its utility, we use subject-specific network profiles to identify brain regions where network expression predicts subject age in the experimental data. Thus, the FSIM is effective at summarizing functional connectivity structure in group-level fMRI, with applications in modeling the relationships between network variability and behavioral/demographic variables. PMID- 27557106 TI - A Note on Divergences. AB - In many areas of neural computation, like learning, optimization, estimation, and inference, suitable divergences play a key role. In this note, we study the conjecture presented by Amari ( 2009 ) and find a counterexample to show that the conjecture does not hold generally. Moreover, we investigate two classes of [Formula: see text]-divergence (Zhang, 2004 ), weighted f-divergence and weighted [Formula: see text]-divergence, and prove that if a divergence is a weighted f divergence, as well as a Bregman divergence, then it is a weighted [Formula: see text]-divergence. This result reduces in form to the main theorem established by Amari ( 2009 ) when [Formula: see text] [Formula: see text]. PMID- 27557107 TI - Learning Polychronous Neuronal Groups Using Joint Weight-Delay Spike-Timing Dependent Plasticity. AB - Polychronous neuronal group (PNG), a type of cell assembly, is one of the putative mechanisms for neural information representation. According to the reader-centric definition, some readout neurons can become selective to the information represented by polychronous neuronal groups under ongoing activity. Here, in computational models, we show that the frequently activated polychronous neuronal groups can be learned by readout neurons with joint weight-delay spike timing-dependent plasticity. The identity of neurons in the group and their expected spike timing at millisecond scale can be recovered from the incoming weights and delays of the readout neurons. The detection performance can be further improved by two layers of readout neurons. In this way, the detection of polychronous neuronal groups becomes an intrinsic part of the network, and the readout neurons become differentiated members in the group to indicate whether subsets of the group have been activated according to their spike timing. The readout spikes representing this information can be used to analyze how PNGs interact with each other or propagate to downstream networks for higher-level processing. PMID- 27557109 TI - Correction: Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar. AB - [This corrects the article DOI: 10.1371/journal.pntd.0004827.]. PMID- 27557108 TI - Genomic data mining reveals a rich repertoire of transport proteins in Streptomyces. AB - BACKGROUND: Streptomycetes are soil-dwelling Gram-positive bacteria that are best known as the major producers of antibiotics used in the pharmaceutical industry. The evolution of exceptionally powerful transporter systems in streptomycetes has enabled their adaptation to the complex soil environment. RESULTS: Our comparative genomic analyses revealed that each of the eleven Streptomyces species examined possesses a rich repertoire of from 761-1258 transport proteins, accounting for 10.2 to 13.7 % of each respective proteome. These transporters can be divided into seven functional classes and 171 transporter families. Among them, the ATP-binding Cassette (ABC) superfamily and the Major Facilitator Superfamily (MFS) represent more than 40 % of all the transport proteins in Streptomyces. They play important roles in both nutrient uptake and substrate secretion, especially in the efflux of drugs and toxicants. The evolutionary flexibility across eleven Streptomyces species is seen in the lineage-specific distribution of transport proteins in two major protein translocation pathways: the general secretory (Sec) pathway and the twin-arginine translocation (Tat) pathway. CONCLUSIONS: Our results present a catalog of transport systems in eleven Streptomyces species. These expansive transport systems are important mediators of the complex processes including nutrient uptake, concentration balance of elements, efflux of drugs and toxins, and the timely and orderly secretion of proteins. A better understanding of transport systems will allow enhanced optimization of production processes for both pharmaceutical and industrial applications of Streptomyces, which are widely used in antibiotic production and heterologous expression of recombinant proteins. PMID- 27557110 TI - A Unique Assemblage of Engraved Plaquettes from Ein Qashish South, Jezreel Valley, Israel: Figurative and Non-Figurative Symbols of Late Pleistocene Hunters Gatherers in the Levant. AB - Three engraved limestone plaquettes from the recently excavated Epipaleolithic open-air site Ein Qashish South in the Jezreel Valley, Israel comprise unique evidence for symbolic behavior of Late Pleistocene foragers in the Levant. The engravings, uncovered in Kebaran and Geometric Kebaran deposits (ca. 23ka and ca. 16.5ka BP), include the image of a bird-the first figurative representation known so far from a pre-Natufian Epipaleolithic-along with geometric motifs such as chevrons, crosshatchings and ladders. Some of the engravings closely resemble roughly contemporary European finds interpreted as "systems of notations" or "artificial memory systems"-records related to timing of seasonal resources and associated aggregation events of nomadic groups. Moreover, similarly looking signs and patterns are well known from the context of the local Natufian-a final Epipaleolithic culture of sedentary or semi-sedentary foragers who started practicing agriculture. The investigation of the engravings found in Ein Qashish South involves conceptualizations developed in studies of European and local parallels, a selection of ethnographic examples and preliminary microscopic observations of the plaquettes. This shows that the figurative and non-figurative images comprise a coherent assemblage of symbols that might have been applied in order to store, share and transmit information related to social and subsistence realms of mobile bands. It further suggests that the site functioned as a locality of groups' aggregation and indicates social complexity of pre-Natufian foragers in the Levant. While alterations in social and subsistence strategies can explain the varying frequency of image use characterizing different areas of the Late Pleistocene world-the apparent similarity in graphics and the mode of their application support the possibility that symbol-mediated behavior has a common and much earlier origin. PMID- 27557111 TI - Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis. AB - BACKGROUND: Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. METHODS: Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. RESULTS: Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). CONCLUSION: Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation. PMID- 27557112 TI - OCT-Based Quantification and Classification of Optic Disc Structure in Glaucoma Patients. AB - PURPOSE: To objectively classify the optic discs of open-angle glaucoma (OAG) patients into Nicolela's four disc types, i.e., focal ischemic (FI), myopic (MY), senile sclerotic (SS), and generalized enlargement (GE), with swept-source optical coherence tomography (SS-OCT). METHODS: This study enrolled 113 eyes of 113 OAG patients (mean age: 62.5 +/- 12.6; Humphrey field analyzer-measured mean deviation: -9.4 +/- 7.3 dB). Newly developed software was used to quantify a total of 20 optic disc parameters in SS-OCT (DRI OCT-1, TOPCON) images of the optic disc. The most suitable reference plane (RP) above the plane of Bruch's membrane opening was determined by comparing, at various RP heights, the SS-OCT measured rim parameters and spectral-domain OCT-measured circumpapillary retinal nerve fiber layer thickness (cpRNFLT), with Pearson's correlation analysis. To obtain a discriminant formula for disc type classification, a training group of 72 eyes of 72 OAG patients and a validation group of 60 eyes of 60 OAG patients were set up. RESULTS: Correlation with cpRNFLT differed with disc type and RP height, but overall, a height of 120 MUm minimized the influence of disc type. Six parameters were most significant for disc type discrimination: disc angle (horizontal), average cup depth, cup/disc ratio, rim-decentering ratio, average rim/disc ratio (upper and lower nasal). Classifying the validation group with these parameters returned an identification rate of 80.0% and a Cohen's Kappa of 0.73. CONCLUSION: Our new, objective SS-OCT-based method enabled us to classify glaucomatous optic discs with high reproducibility and accuracy. PMID- 27557113 TI - Multitemporal Modelling of Socio-Economic Wildfire Drivers in Central Spain between the 1980s and the 2000s: Comparing Generalized Linear Models to Machine Learning Algorithms. AB - The socio-economic factors are of key importance during all phases of wildfire management that include prevention, suppression and restoration. However, modeling these factors, at the proper spatial and temporal scale to understand fire regimes is still challenging. This study analyses socio-economic drivers of wildfire occurrence in central Spain. This site represents a good example of how human activities play a key role over wildfires in the European Mediterranean basin. Generalized Linear Models (GLM) and machine learning Maximum Entropy models (Maxent) predicted wildfire occurrence in the 1980s and also in the 2000s to identify changes between each period in the socio-economic drivers affecting wildfire occurrence. GLM base their estimation on wildfire presence-absence observations whereas Maxent on wildfire presence-only. According to indicators like sensitivity or commission error Maxent outperformed GLM in both periods. It achieved a sensitivity of 38.9% and a commission error of 43.9% for the 1980s, and 67.3% and 17.9% for the 2000s. Instead, GLM obtained 23.33, 64.97, 9.41 and 18.34%, respectively. However GLM performed steadier than Maxent in terms of the overall fit. Both models explained wildfires from predictors such as population density and Wildland Urban Interface (WUI), but differed in their relative contribution. As a result of the urban sprawl and an abandonment of rural areas, predictors like WUI and distance to roads increased their contribution to both models in the 2000s, whereas Forest-Grassland Interface (FGI) influence decreased. This study demonstrates that human component can be modelled with a spatio-temporal dimension to integrate it into wildfire risk assessment. PMID- 27557114 TI - Histone acetyltransferase inhibitors: where art thou? PMID- 27557115 TI - Small Intestinal Angioectasia: Characterization, Risk Factors, and Rebleeding. AB - BACKGROUND: Gastrointestinal angioectasias (AEs) represent the most common vascular malformation within the gastrointestinal tract. This study sought to characterize epidemiologic/comorbid risk factors for AEs, rebleeding, and patterns of anatomic distribution within the small intestine. STUDY: This retrospective observational cohort study included 158 patients with AEs on capsule endoscopy (CE) from 2007 to 2015. Epidemiologic/comorbid data were collected and incorporated into final analysis. Each AE was categorized by location using a small bowel transit time-based quartile system. Rebleeding was evaluated following CE. Multivariate logistic regression was applied to statistically significant factors on univariate analysis to determine independent risk factors for rebleeding. RESULTS: Most lesions were found in the first quartile (67.1%). Rebleeding occurred in 46 (29.7%) of the 156 patients for whom data were available. Rates of rebleeding were significantly higher among older patients (74.4 vs. 67.7 y, P=0.001), those with active bleeding on CE (41.3% vs. 16.5%, P=0.001), those with a history of aortic stenosis (21.7% vs. 9.2%, P=0.033), and those with AEs presents in quartile 3 (26.1% vs. 8.3%, P=0.003). Age, active bleeding on CE, and AE presence in quartile 3 were independently associated with rebleeding in multivariate analysis (P=0.009, 0.023, and 0.008, respectively). CONCLUSIONS: These data help improve our knowledge of AEs regarding risk factors for rebleeding, and utilizes a novel small bowel transit time-based quartile localization method that may simplify future research and comparisons of anatomic distribution and behavior of small bowel AEs. PMID- 27557116 TI - Efficacy of Fine-Needle Aspiration Cytology in the Diagnosis of Primary Thyroid Lymphoma for Elderly Adults. PMID- 27557117 TI - Hand grip strength in juvenile idiopathic arthritis as predictor of disease activity and disability in clinical practice. PMID- 27557118 TI - Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes. AB - BACKGROUND: Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. METHODS: We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. RESULTS: We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. CONCLUSION: We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM. PMID- 27557119 TI - Whole genomic sequence analysis of Bacillus infantis: defining the genetic blueprint of strain NRRL B-14911, an emerging cardiopathogenic microbe. AB - BACKGROUND: We recently reported the identification of Bacillus sp. NRRL B-14911 that induces heart autoimmunity by generating cardiac-reactive T cells through molecular mimicry. This marine bacterium was originally isolated from the Gulf of Mexico, but no associations with human diseases were reported. Therefore, to characterize its biological and medical significance, we sought to determine and analyze the complete genome sequence of Bacillus sp. NRRL B-14911. RESULTS: Based on the phylogenetic analysis of 16S ribosomal RNA (rRNA) genes, sequence analysis of the 16S-23S rDNA intergenic transcribed spacers, phenotypic microarray, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we propose that this organism belongs to the species Bacillus infantis, previously shown to be associated with sepsis in a newborn child. Analysis of the complete genome of Bacillus sp. NRRL B-14911 revealed several virulence factors including adhesins, invasins, colonization factors, siderophores and transporters. Likewise, the bacterial genome encodes a wide range of methyl transferases, transporters, enzymatic and biochemical pathways, and insertion sequence elements that are distinct from other closely related bacilli. CONCLUSIONS: The complete genome sequence of Bacillus sp. NRRL B-14911 provided in this study may facilitate genetic manipulations to assess gene functions associated with bacterial survival and virulence. Additionally, this bacterium may serve as a useful tool to establish a disease model that permits systematic analysis of autoimmune events in various susceptible rodent strains. PMID- 27557120 TI - Prioritization of Zoonotic Diseases in Kenya, 2015. AB - INTRODUCTION: Zoonotic diseases have varying public health burden and socio economic impact across time and geographical settings making their prioritization for prevention and control important at the national level. We conducted systematic prioritization of zoonotic diseases and developed a ranked list of these diseases that would guide allocation of resources to enhance their surveillance, prevention, and control. METHODS: A group of 36 medical, veterinary, and wildlife experts in zoonoses from government, research institutions and universities in Kenya prioritized 36 diseases using a semi quantitative One Health Zoonotic Disease Prioritization tool developed by Centers for Disease Control and Prevention with slight adaptations. The tool comprises five steps: listing of zoonotic diseases to be prioritized, development of ranking criteria, weighting criteria by pairwise comparison through analytical hierarchical process, scoring each zoonotic disease based on the criteria, and aggregation of scores. RESULTS: In order of importance, the participants identified severity of illness in humans, epidemic/pandemic potential in humans, socio-economic burden, prevalence/incidence and availability of interventions (weighted scores assigned to each criteria were 0.23, 0.22, 0.21, 0.17 and 0.17 respectively), as the criteria to define the relative importance of the diseases. The top five priority diseases in descending order of ranking were anthrax, trypanosomiasis, rabies, brucellosis and Rift Valley fever. CONCLUSION: Although less prominently mentioned, neglected zoonotic diseases ranked highly compared to those with epidemic potential suggesting these endemic diseases cause substantial public health burden. The list of priority zoonotic disease is crucial for the targeted allocation of resources and informing disease prevention and control programs for zoonoses in Kenya. PMID- 27557121 TI - Geometrical Measures Obtained from Pretreatment Postcontrast T1 Weighted MRIs Predict Survival Benefits from Bevacizumab in Glioblastoma Patients. AB - BACKGROUND: Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. METHODS: 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE 'rim' geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients. RESULTS: Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ. CONCLUSION: Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results. PMID- 27557122 TI - Vitamin D Intake and Risk of Skin Cancer in US Women and Men. AB - Previous studies suggested a protective effect of vitamin D against skin cancer development. However, epidemiologic studies on orally taken vitamin D and risk of skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) are few. We prospectively evaluated whether total, dietary and supplemental vitamin D intake were associated with skin cancer risk based on 63,760 women in the Nurses' Health Study (1984-2010) and 41,530 men in the Health Professionals Follow-up Study (1986-2010). Dietary information on vitamin D intake was assessed every 2 to 4 years during the follow-up and cumulative averaged intake was used. We used Cox proportional hazard models to compute the hazard ratios (HR) and 95% confidence intervals (CI). Pooled HR of cohort specific results were calculated using a random-effects model. During the follow up, we documented 20,840 BCC, 2,329 SCC and 1,320 melanoma cases. Vitamin D consumption was not associated with the risk of SCC or melanoma but was modestly positively associated with BCC; the pooled HRs of BCC for extreme quintiles of vitamin D intake were 1.10 (95%CI = 1.05-1.15; Ptrend = 0.05) for total vitamin D and 1.13 (95% CI = 1.07 to 1.20; Ptrend <0.01) for dietary vitamin D. Stratified analysis according to sun exposure related factors showed similar results. In conclusion, vitamin D intake was positively associated with risk of BCC, while null associations were found with SCC and melanoma. Our data do not support a beneficial role of orally taken vitamin D on skin cancer carcinogenesis. PMID- 27557123 TI - Revisiting Mitochondrial pH with an Improved Algorithm for Calibration of the Ratiometric 5(6)-carboxy-SNARF-1 Probe Reveals Anticooperative Reaction with H+ Ions and Warrants Further Studies of Organellar pH. AB - Fluorescence measurements of pH and other analytes in the cell rely on accurate calibrations, but these have routinely used algorithms that inadequately describe the properties of indicators. Here, we have established a more accurate method for calibrating and analyzing data obtained using the ratiometric probe 5(6) carboxy-SNARF-1. We tested the implications of novel approach to measurements of pH in yeast mitochondria, a compartment containing a small number of free H+ ions. Our findings demonstrate that 5(6)-carboxy-SNARF-1 interacts with H+ ions inside the mitochondria in an anticooperative manner (Hill coefficient n of 0.5) and the apparent pH inside the mitochondria is ~0.5 unit lower than had been generally assumed. This result, at odds with the current consensus on the mechanism of energy generation in the mitochondria, is in better agreement with theoretical considerations and warrants further studies of organellar pH. PMID- 27557124 TI - Health Service Accessibility and Risk in Cervical Cancer Prevention: Comparing Rural Versus Nonrural Residence in New Mexico. AB - PURPOSE: Multiple intrapersonal and structural barriers, including geography, may prevent women from engaging in cervical cancer preventive care such as screening, diagnostic colposcopy, and excisional precancer treatment procedures. Geographic accessibility, stratified by rural and nonrural areas, to necessary services across the cervical cancer continuum of preventive care is largely unknown. METHODS: Health care facility data for New Mexico (2010-2012) was provided by the New Mexico Human Papillomavirus Pap Registry (NMHPVPR), the first population based statewide cervical cancer screening registry in the United States. Travel distance and time between the population-weighted census tract centroid to the nearest facility providing screening, diagnostic, and excisional treatment services were examined using proximity analysis by rural and nonrural census tracts. Mann-Whitney test (P < .05) was used to determine if differences were significant and Cohen's r to measure effect. FINDINGS: Across all cervical cancer preventive health care services and years, women who resided in rural areas had a significantly greater geographic accessibility burden when compared to nonrural areas (4.4 km vs 2.5 km and 4.9 minutes vs 3.0 minutes for screening; 9.9 km vs 4.2 km and 10.4 minutes vs 4.9 minutes for colposcopy; and 14.8 km vs 6.6 km and 14.4 minutes vs 7.4 minutes for precancer treatment services, all P < .001). CONCLUSION: Improvements in cervical cancer prevention should address the potential benefits of providing the full spectrum of screening, diagnostic and precancer treatment services within individual facilities. Accessibility, assessments distinguishing rural and nonrural areas are essential when monitoring and recommending changes to service infrastructures (eg, mobile versus brick and mortar). PMID- 27557126 TI - Correction: Hybrid Symbiotic Organisms Search Optimization Algorithm for Scheduling of Tasks on Cloud Computing Environment. AB - [This corrects the article DOI: 10.1371/journal.pone.0158229.]. PMID- 27557125 TI - Toxin YafQ Reduces Escherichia coli Growth at Low Temperatures. AB - Toxin/antitoxin (TA) systems reduce metabolism under stress; for example, toxin YafQ of the YafQ/DinJ Escherichia coli TA system reduces growth by cleaving transcripts with in-frame 5'-AAA-G/A-3' sites, and antitoxin DinJ is a global regulator that represses its locus as well as controls levels of the stationary sigma factor RpoS. Here we investigated the influence on cell growth at various temperatures and found that deletion of the antitoxin gene, dinJ, resulted in both reduced metabolism and slower growth at 18 degrees C but not at 37 degrees C. The reduction in growth could be complemented by producing DinJ from a plasmid. Using a transposon screen to reverse the effect of the absence of DinJ, two mutations were found that inactivated the toxin YafQ; hence, the toxin caused the slower growth only at low temperatures rather than DinJ acting as a global regulator. Corroborating this result, a clean deletion of yafQ in the DeltadinJ DeltaKmR strain restored both metabolism and growth at 18 degrees C. In addition, production of YafQ was more toxic at 18 degrees C compared to 37 degrees C. Furthermore, by overproducing all the E. coli proteins, the global transcription repressor Mlc was found that counteracts YafQ toxicity only at 18 degrees C. Therefore, YafQ is more effective at reducing metabolism at low temperatures, and Mlc is its putative target. PMID- 27557127 TI - Integrative Medicine Preferences Among Coccidioidomycosis (Valley Fever) Patients. AB - OBJECTIVES: To understand the extent and modalities of integrative medicine strategies that patients with coccidioidomycosis (valley fever) have incorporated into their treatment regimens. DESIGN: A direct patient survey was distributed, with 100 unique responses, at a single infectious diseases clinic at an academic medical center in Arizona. Eligible patients, defined as those with confirmed coccidioidomycosis or currently under evaluation, were polled on their personal use of 36 integrative medicine modalities. Patients were also asked to indicate their level of fatigue on a 10-point scale in an attempt to correlate levels of fatigue to use of specific integrative medicine modalities. RESULTS: Of the patients surveyed, 64% had used at least one integrative medicine modality, and 53% used two or more, along with conventional medical therapy. The top three modalities were nutrition (39%), massage (27%), and breathing exercises (26%). The mean reported fatigue level was 4.7 on a 10-point scale, with a standard deviation of 3.0. There was no statistically significant association between use of a specific modality and reported level of fatigue. CONCLUSIONS: Nearly two thirds of patients (64%) surveyed had used at least one integrative medicine modality throughout the course of their therapy. Clinicians are probably unaware of the extent to which many patients, including this population, have embraced integrative medicine. Awareness of patients' goal and preferences is valuable in shared clinical decision making. PMID- 27557128 TI - Combination of Bottom-up 2D-LC-MS and Semi-top-down GelFree-LC-MS Enhances Coverage of Proteome and Low Molecular Weight Short Open Reading Frame Encoded Peptides of the Archaeon Methanosarcina mazei. AB - The recent discovery of an increasing number of small open reading frames (sORF) creates the need for suitable analytical technologies for the comprehensive identification of the corresponding gene products. For biological and functional studies the knowledge of the entire set of proteins and sORF gene products is essential. Consequently in the present study we evaluated analytical approaches that will allow for simultaneous analysis of widest parts of the proteome together with the predicted sORF. We performed a full proteome analysis of the methane producing archaeon Methanosarcina mazei strain Go1 cytosolic proteome using a high/low pH reversed phase LC-MS bottom-up approach. The second analytical approach was based on semi-top-down strategy, encompassing a separation at intact protein level using a GelFree system, followed by digestion and LC-MS analysis. A high overlap in identified proteins was found for both approaches yielding the most comprehensive coverage of the cytosolic proteome of this organism achieved so far. The application of the second approach in combination with an adjustment of the search criteria for database searches further led to a significant increase of sORF peptide identifications, finally allowing to detect and identify 28 sORF gene products. PMID- 27557129 TI - Effects of School-Based Educational Interventions for Enhancing Adolescents Abilities in Critical Appraisal of Health Claims: A Systematic Review. AB - BACKGROUND AND OBJECTIVE: Adolescents are frequent media users who access health claims from various sources. The plethora of conflicting, pseudo-scientific, and often misleading health claims in popular media makes critical appraisal of health claims an essential ability. Schools play an important role in educating youth to critically appraise health claims. The objective of this systematic review was to evaluate the effects of school-based educational interventions for enhancing adolescents' abilities in critically appraising health claims. METHODS: We searched MEDLINE, Embase, PsycINFO, AMED, Cinahl, Teachers Reference Centre, LISTA, ERIC, Sociological Abstracts, Social Services Abstracts, The Cochrane Library, Science Citation Index Expanded, Social Sciences Citation Index, and sources of grey literature. Studies that evaluated school-based educational interventions to improve adolescents' critical appraisal ability for health claims through advancing the students' knowledge about science were included. Eligible study designs were randomised and non-randomised controlled trials, and interrupted time series. Two authors independently selected studies, extracted data, and assessed risk of bias in included studies. Due to heterogeneity in interventions and inadequate reporting of results, we performed a descriptive synthesis of studies. We used GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) to assess the certainty of the evidence. RESULTS: Eight studies were included: two compared different teaching modalities, while the others compared educational interventions to instruction as usual. Studies mostly reported positive short-term effects on critical appraisal-related knowledge and skills in favour of the educational interventions. However, the certainty of the evidence for all comparisons and outcomes was very low. CONCLUSION: Educational interventions in schools may have beneficial short-term effects on knowledge and skills relevant to the critical appraisal of health claims. The small number of studies, their heterogeneity, and the predominantly high risk of bias inhibit any firm conclusions about their effects. None of the studies evaluated any long-term effects of interventions. Future intervention studies should adhere to high methodological standards, target a wider variety of school-based settings, and include a process evaluation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42015017936. PMID- 27557130 TI - Phylogenetic Reassessment of Antarctic Tetillidae (Demospongiae, Tetractinellida) Reveals New Genera and Genetic Similarity among Morphologically Distinct Species. AB - Species of Tetillidae are distributed worldwide. However, some genera are unresolved and only a few genera and species of this family have been described from the Antarctic. The incorporation of 25 new COI and 18S sequences of Antarctic Tetillidae to those used recently for assessing the genera phylogeny, has allowed us to improve the resolution of some poorly resolved nodes and to confirm the monophyly of previously identified clades. Classical genera such as Craniella recovered their traditional diagnosis by moving the Antarctic Tetilla from Craniella, where they were placed in the previous family phylogeny, to Antarctotetilla gen. nov. The morphological re-examination of specimens used in the previous phylogeny and their comparison to the type material revealed misidentifications. The proposed monotypic new genus Levantiniella had uncertain phylogenetic relationships depending on the gene partition used [corrected]. Two more clades would require the inclusion of additional species to be formally established as new genera. The parsimony tree based on morphological characters and the secondary structure of the 18S (V4 region) almost completely matched the COI M1-M6 and the COI+18S concatenated phylogenies. Morphological synapomorphies have been identified for the genera proposed. New 15 28S (D3-D5) and 11 COI I3 M11 partitions were exclusively sequenced for the Antarctic species subset. Remarkably, species within the Antarctic genera Cinachyra (C. barbata and C. antarctica) and Antarctotetilla (A. leptoderma, A. grandis, and A. sagitta), which are clearly distinguishable morphologically, were not genetically differentiated with any of the markers assayed. Thus, as it has been reported for other Antarctic sponges, both the mitochondrial and nuclear partitions used did not differentiate species that were well characterized morphologically. Antarctic Tetillidae offers a rare example of genetically cryptic (with the traditional markers used for sponges), morphologically distinct species. PMID- 27557131 TI - Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy. AB - OBJECTIVE: Radiotherapy is planned to achieve the optimal physical dose distribution to the target tumour volume whilst minimizing dose to the surrounding normal tissue. Recent in vitro experimental evidence has demonstrated an important role for intercellular communication in radiobiological responses following non-uniform exposures. This study aimed to model the impact of these effects in the context of techniques involving highly modulated radiation fields or spatially fractionated treatments such as spatially fractionated radiotherapy (GRID). METHODS: Using the small-animal radiotherapy research platform as a key enabling technology to deliver precision imaged-guided radiotherapy, it is possible to achieve spatially modulated dose distributions that model typical clinical scenarios. In this work, we planned uniform and spatially fractionated dose distributions using multiple isocentres with beam sizes of 0.5-5 mm to obtain 50% volume coverage in a subcutaneous murine tumour model and applied a model of cellular response that incorporates intercellular communication to assess the potential impact of signalling effects with different ranges. RESULTS: Models of GRID treatment plans which incorporate intercellular signalling showed increased cell killing within the low-dose region. This results in an increase in the equivalent uniform dose for GRID exposures compared with standard models, with some GRID exposures being predicted to be more effective than uniform delivery of the same physical dose. CONCLUSION: This study demonstrates the potential impact of radiation-induced signalling on tumour cell response for spatially fractionated therapies and identifies key experiments to validate this model and quantify these effects in vivo. Advances in knowledge: This study highlights the unique opportunities now possible using advanced preclinical techniques to develop a foundation for biophysical optimization in radiotherapy treatment planning. PMID- 27557133 TI - Nontargeted analysis of the urine nonpolar sulfateome: a pathway to the nonpolar xenobiotic exposome. AB - RATIONALE: Testing the urine nonpolar sulfateome can enable discovery of xenobiotics that are most likely to be bioactive. This is based on the fact that nonpolar xenobiotics are more likely to enter cells where they tend to undergo metabolism, in part, to sulfates that are then largely excreted into the urine. METHODS: The following sequence of steps, with conditions that achieve high reproducibility, was applied to large human urine samples: (1) competitive nonpolar extraction with a porous extraction paddle; (2) weak anion-exchange extraction with strong organic washing; and (3) ultrahigh-performance liquid chromatography (UHPLC)/negative ion matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometery (MALDI-TOF/TOF-MS) with recording of ions with signal-to-noise (S/N) >= 20 that yielded M-1-80 (loss of SO3 ) or m/z 97 (HSO4- ) upon fragmentation. RESULTS: From a collection of urine samples from six pregnant women, the masses of 1129 putative sulfates were measured. Three lists of candidate compounds (preliminary hits) from these masses were formed by searching METLIN, especially via MATLAB, yielding putative xenobiotic contaminants (35 compounds), steroids (122), and flavonoids (1582). CONCLUSIONS: A new way to reveal some of the nonpolar xenobiotic exposome has been developed that applies to urine samples. The value of the method is to suggest xenobiotics for subsequent targeted analysis in the population of people under study, in order to relate the environment to health and disease. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27557132 TI - Relationships between Parental Education and Overweight with Childhood Overweight and Physical Activity in 9-11 Year Old Children: Results from a 12-Country Study. AB - BACKGROUND: Globally, the high prevalence of overweight and low levels of physical activity among children has serious implications for morbidity and premature mortality in adulthood. Various parental factors are associated with childhood overweight and physical activity. The objective of this paper was to investigate relationships between parental education or overweight, and (i) child overweight, (ii) child physical activity, and (iii) explore household coexistence of overweight, in a large international sample. METHODS: Data were collected from 4752 children (9-11 years) as part of the International Study of Childhood Obesity, Lifestyle and the Environment in 12 countries around the world. Physical activity of participating children was assessed by accelerometry, and body weight directly measured. Questionnaires were used to collect parents' education level, weight, and height. RESULTS: Maternal and paternal overweight were positively associated with child overweight. Higher household coexistence of parent-child overweight was observed among overweight children compared to the total sample. There was a positive relationship between maternal education and child overweight in Colombia 1.90 (1.23-2.94) [odds ratio (confidence interval)] and Kenya 4.80 (2.21-10.43), and a negative relationship between paternal education and child overweight in Brazil 0.55 (0.33-0.92) and the USA 0.54 (0.33-0.88). Maternal education was negatively associated with children meeting physical activity guidelines in Colombia 0.53 (0.33-0.85), Kenya 0.35 (0.19-0.63), and Portugal 0.54 (0.31-0.96). CONCLUSIONS: Results are aligned with previous studies showing positive associations between parental and child overweight in all countries, and positive relationships between parental education and child overweight or negative associations between parental education and child physical activity in lower economic status countries. Relationships between maternal and paternal education and child weight status and physical activity appear to be related to the developmental stage of different countries. Given these varied relationships, it is crucial to further explore familial factors when investigating child overweight and physical activity. PMID- 27557134 TI - Study of reactivity of cyanoacetohydrazonoethyl-N-ethyl-N-methyl benzenesulfonamide: preparation of novel anticancer and antimicrobial active heterocyclic benzenesulfonamide derivatives and their molecular docking against dihydrofolate reductase. AB - This article describes the synthesis of some novel heterocyclic sulfonamides having biologically active thiophene 3, 4, 5, 6, coumarin 8, benzocoumarin 9, thiazole 7, piperidine 10, pyrrolidine 11, pyrazole 14 and pyridine 12, 13. Starting with 4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)-N-ethyl-N methylbenzenesulfonamide (2), which was prepared from condensation of acetophenone derivative 1 with 2-cyanoacetohydrazide. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR and MS spectral data. All the newly synthesized heterocyclic sulfonamides were evaluated as in-vitro anti-breast cancer cell line (MCF7) and as in-vitro antimicrobial agents. Compounds 8, 5 and 11 were more active than MTX reference drug and compounds 12, 7, 4, 14, 5 and 8 were highly potent against Klebsiella pneumonia. Molecular operating environment performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some prepared compounds are suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDBSD:4DFR) with further modification. PMID- 27557135 TI - The Modulation of Mimicry by Ethnic Group-Membership and Emotional Expressions. AB - Mimicry has been ascribed affiliative functions. In three experiments, we used a newly developed social-affective mimicry task (SAMT) to investigate mimicry's modulation by emotional facial expressions (happy, angry) and ethnic group membership (White in-group, Black out-group). Experiment 1 established the main consistent effect across experiments, which was enhanced mimicry to angry out group faces compared to angry in-group faces. Hence the SAMT was useful for experimentally investigating the modulation of mimicry. Experiment 2 demonstrated that these effects were not confounded by general aspects of response conflict, as a Simon task resulted in different response patterns than the SAMT. Experiment 2 and pooled analysis of Experiments 1 and 2 also corroborated the finding of enhanced mimicry to angry out-group faces. Experiment 3 tested whether this effect was related to perceptions of threat, by framing angry persons as physically threatening, or not. Selective enhancement of mimicry to out-group persons framed as physically threatening confirmed this hypothesis. Further support for the role of threat was derived from implicit measures showing, in all experiments, that black persons were more strongly associated with threat. Furthermore, enhanced mimicry was consistently related to response facilitation in the execution of congruent movements. This suggests that mimicry acted as a social congruency signal. Our findings suggest that mimicry may serve as an appeasement signal in response to negative affiliative intent. This extends previous models of mimicry, which have predominantly focused on its role in reciprocating affiliation. It suggests that mimicry might not only be used to maintain and establish affiliative bonds, but also to ameliorate a negative social situation. PMID- 27557136 TI - p-Terphenyl Derivatives from the Endolichenic Fungus Floricola striata. AB - Ten new p-terphenyl derivatives, floricolins A-J (1-10), together with six known compounds (11-16), were isolated from the extract of the endolichenic fungus Floricola striata. Chemical structures of these compounds were elucidated using spectroscopic data (HRESIMS and NMR). Among them, 9 and 10 were enantiomeric mixtures, and their configurations were established by single-crystal X-ray diffraction analysis using Cu Kalpha radiation. Evaluation of the isolated compounds against Candida albicans revealed that the most active compound, 3 (MIC 8 MUg/mL), exerted fungicidal action by destruction of the cell membrane. PMID- 27557137 TI - Whole blood transcriptional profiling comparison between different milk yield of Chinese Holstein cows using RNA-seq data. AB - BACKGROUND: The objective of this research was to investigate the variation of gene expression in the blood transcriptome profile of Chinese Holstein cows associated to the milk yield traits. RESULTS: We used RNA-seq to generate the bovine transcriptome from the blood of 23 lactating Chinese Holstein cows with extremely high and low milk yield. A total of 100 differentially expressed genes (DEGs) (p < 0.05, FDR < 0.05) were revealed between the high and low groups. Gene ontology (GO) analysis demonstrated that the 100 DEGs were enriched in specific biological processes with regard to defense response, immune response, inflammatory response, icosanoid metabolic process, and fatty acid metabolic process (p < 0.05). The KEGG pathway analysis with 100 DEGs revealed that the most statistically-significant metabolic pathway was related with Toll-like receptor signaling pathway (p < 0.05). The expression level of four selected DEGs was analyzed by qRT-PCR, and the results indicated that the expression patterns were consistent with the deep sequencing results by RNA-Seq. Furthermore, alternative splicing analysis of 100 DEGs demonstrated that there were different splicing pattern between high and low yielders. The alternative 3' splicing site was the major splicing pattern detected in high yielders. However, in low yielders the major type was exon skipping. CONCLUSION: This study provides a non invasive method to identify the DEGs in cattle blood using RNA-seq for milk yield. The revealed 100 DEGs between Holstein cows with extremely high and low milk yield, and immunological pathway are likely involved in milk yield trait. Finally, this study allowed us to explore associations between immune traits and production traits related to milk production. PMID- 27557138 TI - Clinical and histopathological effects of presurgical treatment with sunitinib for renal cell carcinoma with inferior vena cava tumor thrombus at a single institution. AB - To evaluate the clinical and histopathological effects of presurgical treatment with sunitinib on inferior vena cava (IVC) tumor thrombus. Between 2010 and 2014, we treated seven patients with renal cell carcinoma and IVC tumor thrombus presurgically with sunitinib. We retrospectively evaluated primitive tumor size, the level of tumor thrombus according to Novick's classification, its distance above the renal vein, thrombus diameter at its widest segment, and histopathological change after sunitinib treatment. Three patients were diagnosed histologically. Percutaneous biopsy of the renal mass before sunitinib treatment was performed in two patients. One patient was diagnosed after sunitinib treatment following nephrectomy. The primitive tumors shrank upon sunitinib therapy in four cases; however, although the caval thrombus was downstaged (from level II to I) in one patient, the level of caval thrombus did not change in five patients and increased in one patient (from level III to IV). We evaluated the histopathological effects in two patients. In one patient, the IVC tumor thrombus was mostly replaced with necrotic tissue, but its thrombus level was not downstaged. In the other patient, the IVC tumor thrombus was downstaged, but tumor thrombus was not replaced with necrotic tissue and viable tumor cells remained. Presurgical treatment with sunitinib for renal cell carcinoma with IVC tumor thrombus appears to have limited effect on IVC tumor thrombus, in contrast to its effects on primitive tumor shrinkage. In the absence of evidence of presurgical benefits from prospective studies, this treatment may not be systematically advisable. PMID- 27557139 TI - Chamaejasmine induces apoptosis in HeLa cells through the PI3K/Akt signaling pathway. AB - Chamaejasmine is one of the major bioactive components of Stellera chamaejasme L, which is a Chinese traditional herbal medicine that has been used widely in the treatment of cancer. The aim of this study is to investigate the potential effect of chamaejasmine on cervical cancer cells and elucidate the underlying mechanisms of action. We first examined the antitumor activity of chamaejasmine both in vitro and in vivo. In the following experiments with HeLa cells, cell apoptosis and ultrastructure changes were assessed by flow cytometry and transmission electron microscopy, respectively. The effects of chamaejasmine on reactive oxygen species production and mitochondrial membrane potential (Deltapsim) were examined using 2',7'-dichlorohydrofluorescein and rhodamine-123 staining. The mRNA and protein levels of apoptosis-related proteins were detected by real-time PCR and western blot. The activity of caspases 3, 8, and 9 was measured using the corresponding assay kit. The effect of chamaejasmine on the phosphoinositide 3 kinase (PI3K)/Akt pathway was evaluated by luciferase assay and western blot, and further confirmed in Akt overexpressing HeLa cells. We found that chamaejasmine has potent antitumor effects on cervical cancer cell lines both in vitro and in vivo. Mechanistic studies showed that chamaejasmine could induce apoptosis in HeLa cells, and this apoptosis-inducing effect may be mediated through the suppression of PI3K/Akt signaling cascades. These findings not only indicate the therapeutic potential of chamaejasmine for cervical cancer, but provide valuable insight into its mechanism of action. PMID- 27557140 TI - The TYMS-TSER polymorphism is associated with toxicity of low-dose capecitabine in patients with advanced gastrointestinal cancer. AB - Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of different genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with the outcome of a low-dose capecitabine schedule. Genotyping of DPYD IVS14+1 G>A, MTHFR C677T, and A1298C single nucleotide polymorphisms was performed by pyrosequencing technology. A PCR technique was used for genotyping TYMS-TSER. Using peripheral blood mononuclear cells, we also evaluated the 5-FU degradation rate, which determines the net result of all the enzymatic transformation of 5-FU, in terms of the amount of drug consumed by the cells in a time unit. The association of these variables with clinical outcome was evaluated using multivariate logistic regression analysis. Eighty-four patients with metastatic gastrointestinal cancer, who had been treated with a low-dose fluoropyrimidine schedule, as a rescue therapy were included in the study. The TSER 2R/2R genotype was significantly associated with both hematologic (odds ratio=7.90, P=0.002) and gastrointestinal toxicity (odds ratio=3.24, P=0.009). Because DPYD IVS14 G>A single-nucleotide polymorphism was not observed in the cohort, it was excluded from the statistical analysis. No significant association was detected between clinical outcome and both MTHFR polymorphisms and the 5-FU degradation rate. In the advanced setting of cancer care, high attention should be paid toward avoiding toxicity and worsening of quality of life. Although metronomic chemotherapy is generally well tolerated, treatment toxicity nonetheless does occur. Our data suggest a possible role of the TSER 2R/2R polymorphism as a predictive marker of toxicity in patients treated with low-dose capecitabine. PMID- 27557141 TI - Thyroid disorders in Brazil: time for action. PMID- 27557142 TI - Blood pressure levels and body mass index in Brazilian adults with Down syndrome. AB - CONTEXT AND OBJECTIVE: Increased life expectancy among people with Down syndrome (DS) has introduced new environmental factors that may affect blood pressure (BP) and/or lead to obesity in this population. The aim here was to investigate BP levels and body mass index (BMI) in adults with DS, correlating these data with the patients' sex and age. DESIGN AND SETTING: Analytical cross-sectional observational study conducted in special schools in Curitiba (PR), Brazil. METHODS: 97 adult patients were included. BP was measured in accordance with the established guidelines. BMI was calculated by dividing the weight by the height squared (kg/m2). RESULTS: Sex had no influence on BMI; nor did systolic BP (SBP) or diastolic BP (DBP). The age range was from 18 to 56 years. No correlation was observed between increasing age and greater BMI or BP. Eighty-six individuals (88.7%) presented normal BP, eleven (11.3%) prehypertension and none hypertension. Twenty patients (20.4%) presented BP lower than 90 * 60 mmHg. BMI ranged from 18 to 48 kg/m2 (mean of 28.8 +/- 3.92 kg/m2): 21.9% had normal weight; 40.7% were overweight; and 25.3% had obesity class I, 9.9% class II and 2.2% class III. Higher BMI was associated with significantly greater SBP and DBP (P = 0.0175 and P = 0.0015). CONCLUSION: Sex and age did not influence SBP, DBP or BMI in Brazilian adults with DS. Higher BMI was associated with greater BP (both systolic and diastolic). PMID- 27557143 TI - Hematological approaches to multiple myeloma: trends from a Brazilian subset of hematologists. A cross-sectional study. AB - CONTEXT AND OBJECTIVE: For the last nine years, hematologists and oncologists have gathered annually at an educational symposium organized by a Brazilian and an American hospital. During the 2015 Board Review, a survey among the attendees evaluated the differences in management and treatment methods for multiple myeloma (MM). DESIGN AND SETTING: Cross-sectional study during an educational hematology symposium in Sao Paulo, Brazil. METHODS: Hematologists present at the symposium gave responses to an electronic survey by means of mobile phone. RESULTS: Among the 350 attendees, 217 answered the questionnaire. Most of the participants believed that immunotargeting agents (iTA) might be effective for slowing MM progression in heavily pretreated patients (67%) and that continued exposure to therapy might lead to emergence of resistant clones in patients with MM (76%). Most of the physicians use maintenance therapy after hematopoietic stem cell transplantation (95%) and 45% of them would further restrict it to post transplantation patients with underlying high-risk disease. The first-line drugs used for transplantation-ineligible patients (TI-MM) were bortezomib-thalidomide dexamethasone (31%), bortezomib-dexamethasone (28%), lenalidomide-dexamethasone (Rd; 17%) and melphalan-based therapy (10%). Lenalidomide was the drug of choice for post-transplantation maintenance for half of the participants. No significant differences were observed regarding age or length of experience. CONCLUSION: The treatment choices for TI-MM patients were highly heterogenous and the melphalan based regimen represented only 10% of the first-line options. Use of maintenance therapy after transplantation was a common choice. Some results from the survey were divergent from the evidence in the literature. PMID- 27557144 TI - Perspectives for treating Alzheimer's disease: a review on promising pharmacological substances. AB - CONTEXT AND OBJECTIVE: Dementia is a syndrome characterized by functional and cognitive decline. Alzheimer's disease (AD) is one of the most common causes of dementia and has high prevalence among the elderly. It is known that there is no drug capable of interfering with the course of the disease. Research on treatments for AD has been marked by the appearance of new drugs and their abandonment. This study aimed to describe drugs that have been studied with regard to treating AD and which are capable of influencing the course of the disease. DESIGN AND SETTING: Narrative review on original articles published worldwide. METHODS: A systematized search was conducted in the PubMed/MEDLINE, Cochrane Library/Cochrane and SciELO/Bireme databases. The descriptors "Molecular Mechanisms of Pharmacological Action" and "Drug Therapy" were each combined with the descriptor "Alzheimer disease". All of these can be found in MeSH and DeCS. These descriptors were used alone or in combination, and a filter specifying publication between January 2009 and October 2015 in English, Spanish or Portuguese was set. RESULTS: 6,888 articles were found, of which 37 were included in this review; 70.3% of the articles selected were of good quality with low or unclear risk of bias. 86 drugs were considered promising for AD treatment and these were classified into 20 pharmacological categories. CONCLUSION: There are no drugs capable of influencing the course of AD such that treatments are safe and effective. However, immunomodulators stood out as promising, given their effectiveness and quality in the articles analyzed. PMID- 27557145 TI - Pilates for low back pain. AB - BACKGROUND: Non-specific low back pain is a major health problem worldwide. Interventions based on exercises have been the most commonly used treatments for patients with this condition. Over the past few years, the Pilates method has been one of the most popular exercise programmes used in clinical practice. OBJECTIVES: To determine the effects of the Pilates method for patients with non specific acute, subacute or chronic low back pain. METHODS: SEARCH METHODS: We conducted the searches in CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro and SPORTDiscus from the date of their inception to March 2014. We updated the search in June 2015 but these results have not yet been incorporated. We also searched the reference lists of eligible papers as well as six trial registry websites. We placed no limitations on language or date of publication. SELECTION CRITERIA: We only included randomized controlled trials that examined the effectiveness of Pilates intervention in adults with acute, subacute or chronic non-specific low back pain. The primary outcomes considered were pain, disability, global impression of recovery and quality of life. DATA COLLECTION AND ANALYSIS: Two independent raters performed the assessment of risk of bias in the included studies using the 'Risk of bias' assessment tool recommended by The Cochrane Collaboration. We also assessed clinical relevance by scoring five questions related to this domain as 'yes', 'no' or 'unclear'. We evaluated the overall quality of evidence using the GRADE approach and for effect sizes we used three levels: small (mean difference (MD) < 10% of the scale), medium (MD 10% to 20% of the scale) or large (MD > 20% of the scale). We converted outcome measures to a common 0 to 100 scale when different scales were used. MAIN RESULTS: The search retrieved 126 trials; 10 fulfilled the inclusion criteria and we included them in the review (a total sample of 510 participants). Seven studies were considered to have low risk of bias, and three were considered as high risk of bias.A total of six trials compared Pilates to minimal intervention. There is low quality evidence that Pilates reduces pain compared with minimal intervention, with a medium effect size at short-term follow-up (less than three months after randomization) (MD -14.05, 95% confidence interval (CI) -18.91 to -9.19). For intermediate-term follow-up (at least three months but less than 12 months after randomization), two trials provided moderate quality evidence that Pilates reduces pain compared to minimal intervention, with a medium effect size (MD 10.54, 95% CI -18.46 to -2.62). Based on five trials, there is low quality evidence that Pilates improves disability compared with minimal intervention, with a small effect size at short-term follow-up (MD -7.95, 95% CI -13.23 to 2.67), and moderate quality evidence for an intermediate-term effect with a medium effect size (MD -11.17, 95% CI -18.41 to -3.92). Based on one trial and low quality evidence, a significant short-term effect with a small effect size was reported for function (MD 1.10, 95% CI 0.23 to 1.97) and global impression of recovery (MD 1.50, 95% CI 0.70 to 2.30), but not at intermediate-term follow-up for either outcome.Four trials compared Pilates to other exercises. For the outcome pain, we presented the results as a narrative synthesis due to the high level of heterogeneity. At short-term follow-up, based on low quality evidence, two trials demonstrated a significant effect in favour of Pilates and one trial did not find a significant difference. At intermediate-term follow-up, based on low quality evidence, one trial reported a significant effect in favour of Pilates, and one trial reported a non-significant difference for this comparison. For disability, there is moderate quality evidence that there is no significant difference between Pilates and other exercise either in the short term (MD -3.29, 95% CI -6.82 to 0.24) or in the intermediate term (MD -0.91, 95% CI -5.02 to 3.20) based on two studies for each comparison. Based on low quality evidence and one trial, there was no significant difference in function between Pilates and other exercises at short-term follow-up (MD 0.10, 95% CI -2.44 to 2.64), but there was a significant effect in favour of other exercises for intermediate-term function, with a small effect size (MD -3.60, 95% CI -7.00 to -0.20). Global impression of recovery was not assessed in this comparison and none of the trials included quality of life outcomes. Two trials assessed adverse events in this review, one did not find any adverse events, and another reported minor events. AUTHORS CONCLUSIONS: We did not find any high quality evidence for any of the treatment comparisons, outcomes or follow-up periods investigated. However, there is low to moderate quality evidence that Pilates is more effective than minimal intervention for pain and disability. When Pilates was compared with other exercises we found a small effect for function at intermediate-term follow-up. Thus, while there is some evidence for the effectiveness of Pilates for low back pain, there is no conclusive evidence that it is superior to other forms of exercises. The decision to use Pilates for low back pain may be based on the patient's or care provider's preferences, and costs. PMID- 27557146 TI - Yoga for asthma. AB - BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. METHODS: SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardized mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarized the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 liters, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I2 = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I2 = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma. PMID- 27557148 TI - Correction: Emergency Department Visits and Inpatient Admissions Associated with Priapism among Males with Sickle Cell Disease in the United States, 2006-2010. AB - [This corrects the article DOI: 10.1371/journal.pone.0153257.]. PMID- 27557147 TI - Identification of rifampin-regulated functional modules and related microRNAs in human hepatocytes based on the protein interaction network. AB - BACKGROUND: In combination with gene expression profiles, the protein interaction network (PIN) constructs a dynamic network that includes multiple functional modules. Previous studies have demonstrated that rifampin can influence drug metabolism by regulating drug-metabolizing enzymes, transporters, and microRNAs (miRNAs). Rifampin induces gene expression, at least in part, by activating the pregnane X receptor (PXR), which induces gene expression; however, the impact of rifampin on global gene regulation has not been examined under the molecular network frameworks. METHODS: In this study, we extracted rifampin-induced significant differentially expressed genes (SDG) based on the gene expression profile. By integrating the SDG and human protein interaction network (HPIN), we constructed the rifampin-regulated protein interaction network (RrPIN). Based on gene expression measurements, we extracted a subnetwork that showed enriched changes in molecular activity. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG), we identified the crucial rifampin-regulated biological pathways and associated genes. In addition, genes targeted by miRNAs that were significantly differentially expressed in the miRNA expression profile were extracted based on the miRNA-gene prediction tools. The miRNA-regulated PIN was further constructed using associated genes and miRNAs. For each miRNA, we further evaluated the potential impact by the gene interaction network using pathway analysis. RESULTS AND DISCCUSSION: We extracted the functional modules, which included 84 genes and 89 interactions, from the RrPIN, and identified 19 key rifampin-response genes that are associated with seven function pathways that include drug response and metabolism, and cancer pathways; many of the pathways were supported by previous studies. In addition, we identified that a set of 6 genes (CAV1, CREBBP, SMAD3, TRAF2, KBKG, and THBS1) functioning as gene hubs in the subnetworks that are regulated by rifampin. It is also suggested that 12 differentially expressed miRNAs were associated with 6 biological pathways. CONCLUSIONS: Our results suggest that rifampin contributes to changes in the expression of genes by regulating key molecules in the protein interaction networks. This study offers valuable insights into rifampin-induced biological mechanisms at the level of miRNAs, genes and proteins. PMID- 27557149 TI - Time-Dependent Changes in Dural Enhancement Associated With Spontaneous Intracranial Hypotension. AB - OBJECTIVE: The objective of our study was to determine whether the presence of individual imaging signs of spontaneous intracranial hypotension (SIH) is correlated with increasing duration of headache symptoms. Of particular interest is the relationship of symptom duration to dural enhancement because it is the most commonly identified imaging sign in patients with SIH. MATERIALS AND METHODS: Eighty-nine patients with SIH who underwent pretreatment brain MRI and total-spine CT myelography and whose medical record included data on the duration of clinical symptoms were included in this cross-sectional retrospective study. Brain imaging was reviewed for the presence of dural enhancement, brain sagging, and the "venous distention" sign. CT myelograms were assessed for CSF leak. If present, a leak was subcategorized as a high-flow or low-flow leak. Differences in headache duration between subjects with and those without individual imaging signs were compared. RESULTS: Subjects without dural enhancement on brain MRI had a longer average duration of symptoms than those with dural enhancement present (average symptom duration: 45.3 +/- 59.0 [SD] vs 15.1 +/- 33.0 weeks, respectively; p = 0.002). No difference in symptom duration was observed between subjects whose MRI studies showed and those whose MRI studies did not show brain sagging (p = 0.10) or the venous distention sign (p = 0.21). The presence of a CSF leak on CT myelography was not associated with symptom duration (p = 0.56) except in the subgroup of patients with low-flow leaks. CONCLUSION: Increasing symptom duration in SIH is associated with decreased prevalence of abnormal dural enhancement on brain MRI. Because dural enhancement is considered a hallmark imaging feature of this condition, its absence may exacerbate the problem of underdiagnosis in chronic cases of SIH. PMID- 27557150 TI - Sleep disturbances and upregulation of brain arousal during daytime in depressed versus non-depressed elderly subjects. AB - OBJECTIVES: Although patients with depression often suffer from sleep disturbances, most of them are not sleepy. Upregulation of brain arousal has been proposed as pathophysiological mechanism explaining sleep disturbances, inner tension, autonomic hyperarousal and anhedonia in depression. The aim of the current study was to examine the association between night-time sleep disturbances and brain arousal regulation the next day in depressed versus non depressed subjects. METHODS: Twenty-eight elderly subjects (21 female; age = 70.5 +/- 4.4 years) with depressive syndromes without psychotropic medication, and 28 controls (22 female; age = 70.9 +/- 4.5 years), underwent a 15-min resting electroencephalogram; the Vigilance Algorithm Leipzig (VIGALL 2.1) provided an objective measure of brain arousal regulation. Sleep disturbances were assessed by a validated and self-rated sleep questionnaire. RESULTS: In the depressive group, but not in controls, more sleep disturbances were associated with a higher brain arousal stability score (high score corresponds to upregulation) the next day (sleep onset latency: rs = 0.69, P < .0001; sleep quality: rs = -0.59, P < .001). CONCLUSIONS: The data confirm the hypothesis that in persons with depressive syndromes sleep disturbances are related to upregulation of brain arousal the next day. This finding is in line with the concept that dysregulation of brain arousal is a central pathophysiological aspect in depression. PMID- 27557151 TI - An efficient method for the application of PHA-poor solvents to extract polyhydroxybutyrate from Cupriavidus necator. AB - There are many published studies presenting ethanol and acetone as PHAs-poor solvents, where these two solvents are shown to dissolve <2% (w/v) of PHAs at low temperatures. In this study, the suitability of ethanol and acetone for the recovery of PHB at different temperatures (from room temperature to near boiling point) in Cupriavidus necator was investigated. Experiments were performed using response surface methodology to examine the effects of different temperatures and heating incubation times on recovery percentage using the two solvents. The highest recovery percentage (92.3%) and product purity (up to 99%) were obtained with ethanol-assisted extraction at 76 degrees C for 32 min of incubation time. Under these conditions the extracted PHB exhibited a molecular mass of 1.2 * 106 . The present strategy showed that at temperatures near its boiling point, ethanol, as a nonhalogenated solvent, represents a good alternative to halogenated solvents, like chloroform, when PHB recovery is concerned. DSC analysis showed good thermal properties for ethanol- and acetone-extracted biopolymers. GC and 1 H NMR analysis confirmed the extracted biopolymer to be polyhydroxybutyrate of good purity. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1480-1486, 2016. PMID- 27557152 TI - Germination Ecology and Seed Dispersal of a Critically Endangered Plant: A Case Study of Pomaderris vacciniifolia (Round-Leaf Pomaderris). AB - Change in ecosystem disturbance regimes from human land-use poses a worldwide problem for management of rare species. Two important types of disturbance influencing the persistence of species in Australian ecosystems are habitat fragmentation and fire. In this study, seed dispersal and the germination ecology of Pomaderris vacciniifolia-a critically endangered, rare endemic Australian shrub-were examined to identify likely influences of fire and fragmentation on the decline of populations. The response of seed germination to simulated effects of wildfire and canopy openings was investigated, as was the unaided dispersal capability of seeds from parent plants. A significant increase in germination rate was observed following 100 degrees C heat treatment to seeds, while smoke and light exposure had little influence. Seed imbibition was strongly influenced by heat treatment. The findings indicate a likely positive post-fire germination response, with implications for recruitment success determined by moisture availability following fire. Unaided seed dispersal was limited, which partly explains the apparent decline of populations. Understanding disturbance requirements for threatened species, and subsequent management of landscapes for disturbance, will aid conservation of rare species throughout the world. PMID- 27557153 TI - Transport Properties of the 1-Hexyl-3-methylimidazolium Bis(trifluoromethylsulfonyl)amide-Trichloromethane Binary System: Indication of Trichloromethane Segregation. AB - Self-diffusion coefficients and electrical conductivity were studied for the binary system 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide trichloromethane ([C6mim][NTf2]-CHCl3) as a function of composition and temperature. Self-diffusion coefficients of cation and anion are identical for ionic liquid mole fractions xIL < 0.95. The self-diffusion coefficient of CHCl3 is consistently larger than that of the ions by a factor of 4. A double logarithmic plot for the ratio of self-diffusion coefficient and temperature versus viscosity is linear for ionic liquid mole fractions 0.1 < xIL < 0.9 indicating (a) a fractional Stokes-Einstein applies where self-diffusion is inverse proportional to some power b of viscosity (D ~ eta(-b)) and (b) single average length scales are associated with the mass transport of [C6mim][NTf2] and CHCl3. However, the obtained length scale for CHCl3 is unreasonably small, which is indicative of CHCl3 segregation. The molar conductivity displays a maximum near xIL = 0.2. Evaluation of the ionicity from molar conductivity and self diffusion coefficients indicates a gradual speciation change from charged species to neutral species for xIL < 0.5. The temperature dependencies of self-diffusion and molar conductivity follow Arrhenius behavior. The obtained xIL-dependent activation energies are found to be linear for molar conductivity and largest for the cation and anion self-diffusion coefficients. The activation energies for the self-diffusion of CHCl3 appear to be identical with those obtained from fluidity data. PMID- 27557154 TI - A novel indirect method for capturing involuntary musical imagery under varying cognitive load. AB - Involuntary musical imagery (INMI), i.e the internal experience of a repetitive musical fragment, is one of the most ubiquitous forms of spontaneous cognition. Findings regarding the relationship between INMI and cognitive load are conflicting. In the present study, 200 participants watched and evaluated two non dialogue, music-only film trailers. Subsequently, they either closed their eyes for 5 min (baseline), or engaged in one of three dot tasks of varying challenge and attentional demand (low, medium, and high cognitive load). Finally, they completed a novel "Mind Activity Questionnaire", which allows for indirect INMI sampling rather than direct questioning. The same questionnaire was completed 24 hours later. Overall, a significant negative linear trend was found. At baseline, 65% of people reported experiencing INMI. This rate decreased to 32.5% in the low load condition with further reductions observed in the medium and high conditions, which did not differ significantly from each other. INMI frequency and duration followed the same pattern as the induction rates. In the 24-hour follow-up, 21% of participants reported INMI experiences. This study supports the hypothesis that INMI occurrence, frequency, and duration relate to spare cognitive capacity and demonstrates an ecologically valid laboratory paradigm for covertly inducing and documenting INMI experiences. PMID- 27557155 TI - Career guide: Asia-Pacific. PMID- 27557156 TI - Japan. PMID- 27557157 TI - Australia. PMID- 27557158 TI - Relocating science. PMID- 27557159 TI - South Korea. PMID- 27557160 TI - India. PMID- 27557161 TI - Singapore. PMID- 27557162 TI - New Zealand. PMID- 27557163 TI - China. PMID- 27557164 TI - Systematic review of risk prediction models for diabetes after bariatric surgery. AB - BACKGROUND: Diabetes remission is an important outcome after bariatric surgery. The purpose of this study was to identify risk prediction models of diabetes remission after bariatric surgery. METHODS: A systematic literature review was performed in MEDLINE, MEDLINE-In-Process, Embase and the Cochrane Central Register of Controlled Trials databases in April 2015. All English-language full text published derivation and validation studies for risk prediction models on diabetic outcomes after bariatric surgery were included. Data extraction included population, outcomes, variables, intervention, model discrimination and calibration. RESULTS: Of 2330 studies retrieved, eight met the inclusion criteria. Of these, six presented development of risk prediction models and two reported validation of existing models. All included models were developed to predict diabetes remission. Internal validation using tenfold validation was reported for one model. Two models (ABCD score and DiaRem score) had external validation using independent patient cohorts with diabetes remission assessed at 12 and 14 months respectively. Of the 11 cohorts included in the eight studies, calibration was not reported in any cohort, and discrimination was reported in two. CONCLUSION: A variety of models are available for predicting risk of diabetes following bariatric surgery, but only two have undergone external validation. PMID- 27557165 TI - Solvothermal-Etching Process Induced Ti-Doped Fe2O3 Thin Film with Low Turn-On Voltage for Water Splitting. AB - In this work, a thinning process of hematite film accompanied by simultaneous titanium (Ti) doping has been demonstrated. Ti(4+) ion was incorporated into ultrathin Fe2O3 film by solvothermally etching a hematite film fabricated on titanium nanorod array substrate. As a consequence, the onset potential (Von) of oxygen evolution reaction for final ultrathin Ti-doped Fe2O3 film shifted toward cathodic substantially, a very low Von of 0.48 VRHE was realized, approximately 0.53 V cathodic shift of the hematite film. Working mechanisms were investigated from both kinetic and thermodynamic ways. The ultrathin Ti-doped Fe2O3 film exhibited reduced Tafel slope and higher generated photovoltage than the pristine Fe2O3 electrode. Moreover, the highly doped Fe2O3 resulted in significant reduction of charge-transfer resistance at the Fe2O3?electrolyte interface. The drastic cathodic-shift Von is believed to be a result of combined factors including thermodynamic contribution, improved surface reaction kinetics, as well as facilitated charge transfer across bulk and interface. PMID- 27557166 TI - Reciprocity breaking during nonlinear propagation of adapted beams through random media. AB - Adaptive optics (AO) systems rely on the principle of reciprocity, or symmetry with respect to the interchange of point sources and receivers. These systems use the light received from a low power emitter on or near a target to compensate phase aberrations acquired by a laser beam during linear propagation through random media. If, however, the laser beam propagates nonlinearly, reciprocity is broken, potentially undermining AO correction. Here we examine the consequences of this breakdown, providing the first analysis of AO applied to high peak power laser beams. While discussed for general random and nonlinear media, we consider specific examples of Kerr-nonlinear, turbulent atmosphere. PMID- 27557167 TI - Analytical description of 3D optical pulse diffraction by a phase-shifted Bragg grating. AB - Diffraction of a three-dimensional (3D) spatiotemporal optical pulse by a phase shifted Bragg grating (PSBG) is considered. The pulse diffraction is described in terms of signal transmission through a linear system with a transfer function determined by the reflection or transmission coefficient of the PSBG. Resonant approximations of the reflection and transmission coefficients of the PSBG as functions of the angular frequency and the in-plane component of the wave vector are obtained. Using these approximations, a hyperbolic partial differential equation (Klein-Gordon equation) describing a general class of transformations of the incident 3D pulse envelope is derived. A solution to this equation is found in the form of a convolution integral. The presented rigorous simulation results fully confirm the proposed theoretical description. The obtained results may find application in the design of new devices for spatiotemporal pulse shaping and for optical information processing and analog optical computing. PMID- 27557168 TI - Effect of anatomical noise on the detectability of cone beam CT images with different slice direction, slice thickness, and volume glandular fraction. AB - We investigate the effect of anatomical noise on the detectability of cone beam CT (CBCT) images with different slice directions, slice thicknesses, and volume glandular fractions (VGFs). Anatomical noise is generated using a power law spectrum of breast anatomy, and spherical objects with diameters from 1mm to 11mm are used as breast masses. CBCT projection images are simulated and reconstructed using the FDK algorithm. A channelized Hotelling observer (CHO) with Laguerre Gauss (LG) channels is used to evaluate detectability for the signal-known exactly (SKE) binary detection task. Detectability is calculated for various slice thicknesses in the transverse and longitudinal planes for 15%, 30% and 60% VGFs. The optimal slice thicknesses that maximize the detectability of the objects are determined. The results show that the beta value increases as the slice thickness increases, but that thicker slices yield higher detectability in the transverse and longitudinal planes, except for the case of a 1mm diameter spherical object. It is also shown that the longitudinal plane with a 0.1mm slice thickness provides higher detectability than the transverse plane, despite its higher beta value. With optimal slice thicknesses, the longitudinal plane exhibits better detectability for all VGFs and spherical objects. PMID- 27557169 TI - Three-dimensional shear wave imaging based on full-field laser speckle contrast imaging with one-dimensional mechanical scanning. AB - The high imaging resolution and motion sensitivity of optical-based shear wave detection has made it an attractive technique in biomechanics studies with potential for improving the capabilities of shear wave elasticity imaging. In this study we implemented laser speckle contrast imaging for two-dimensional (X Z) tracking of transient shear wave propagation in agarose phantoms. The mechanical disturbances induced by the propagation of the shear wave caused temporal and spatial fluctuations in the local speckle pattern, which manifested as local blurring. By mechanically moving the sample in the third dimension (Y), and performing two-dimensional shear wave imaging at every scan position, the three-dimensional shear wave velocity distribution of the phantom could be reconstructed. Based on comparisons with the reference shear wave velocity measurements obtained using a commercial ultrasound shear wave imaging system, the developed system can estimate the shear wave velocity with an error of less than 6% for homogeneous phantoms with shear moduli ranging from 1.52 kPa to 7.99 kPa. The imaging sensitivity of our system makes it capable of measuring small variations in shear modulus; the estimated standard deviation of the shear modulus was found to be less than 0.07 kPa. A submillimeter spatial resolution for three-dimensional shear wave imaging has been achieved, as demonstrated by the ability to detect a 1-mm-thick stiff plate embedded inside heterogeneous agarose phantoms. PMID- 27557170 TI - Iterated unscented Kalman filter for phase unwrapping of interferometric fringes. AB - A fresh phase unwrapping algorithm based on iterated unscented Kalman filter is proposed to estimate unambiguous unwrapped phase of interferometric fringes. This method is the result of combining an iterated unscented Kalman filter with a robust phase gradient estimator based on amended matrix pencil model, and an efficient quality-guided strategy based on heap sort. The iterated unscented Kalman filter that is one of the most robust methods under the Bayesian theorem frame in non-linear signal processing so far, is applied to perform simultaneously noise suppression and phase unwrapping of interferometric fringes for the first time, which can simplify the complexity and the difficulty of pre filtering procedure followed by phase unwrapping procedure, and even can remove the pre-filtering procedure. The robust phase gradient estimator is used to efficiently and accurately obtain phase gradient information from interferometric fringes, which is needed for the iterated unscented Kalman filtering phase unwrapping model. The efficient quality-guided strategy is able to ensure that the proposed method fast unwraps wrapped pixels along the path from the high quality area to the low-quality area of wrapped phase images, which can greatly improve the efficiency of phase unwrapping. Results obtained from synthetic data and real data show that the proposed method can obtain better solutions with an acceptable time consumption, with respect to some of the most used algorithms. PMID- 27557171 TI - Lens-free laser nanopatterning of large-scale metal film areas with structured light for biosensing applications. AB - Pulsed laser nanotexturing of metal films represents an ultra-fast, high performance and cost-effective processing technology for fabrication of various functional surfaces widely used in plasmonics, biosensing, and photovoltaics. However, this approach usually requires high-NA lenses to focus a laser beam onto a few-micron spot as well as a micropositioning platform to move this spot along the sample surface, which increases the cost of the produced functional surfaces and limits the performance of laser-assisted nanotexturing techniques. In this paper we report on a laser-assisted technology for the fabrication of large-scale nanotextured metal substrates. In our approach, speckle-modulated patterns obtained by passing nanosecond laser pulses through the simplest diffusive object were utilized to cover a thin gold film with closely packed micron-sized structures - nanojets, nanobumps and through holes - previously reported only for single-shot nanoablation with tightly focused laser beams. The presented easy-to implement technology, being one of the simplest of ever reported, since it requires neither focusing lenses nor micropositioning platforms, was shown to provide a way to pattern millimeter-size areas with the nano-sized jets at an average recording density of 35?103 nanostructures per square millimeter and an average recording speed of 4.5.103 nanostructures per pulse. The fabricated nanotextured Au substrates were shown to yield spatially uniform surface-enhanced fluorescence signals from the Rhodamine 6G organic dye with an averaged 5.3-fold enhancement factor as compared with non treated Au surface. PMID- 27557172 TI - Linewidth suppression mechanism of self-injection locked single-frequency fiber laser. AB - Linewidth suppression mechanism of the self-injection locked single-frequency fiber laser (SFFL) is investigated theoretically and experimentally. An analytical model based on the semi-phenomenological approach is built up to characterize the optical feedback in SFFL. According to the theoretical prediction, the linewidth tends to be reduced with longer external cavity photon lifetime. Experimentally, a 200-Hz linewidth self-injection locked SFFL is achieved with 101 m long delay fiber, which agrees well with the theoretical simulation. The model provides a new perspective to understand the mechanism of linewidth reduction of self-injection locked SFFL. PMID- 27557173 TI - Complex dynamics of a fiber laser in non-stationary pulsed operation. AB - Conventional mode locking is characterized by the generation of a stable train of optical pulses. Even in the noise-like pulsing regime of fiber lasers, sometimes described as partial mode locking, a periodic train of waveforms is still generated. In this work we study the dynamics of a figure-eight fiber laser away from the stable noise-like pulsing regime. By analyzing sequences of time-domain measurements performed with ns resolution, we reveal a wide range of puzzling dynamics, in which sub-structures emerge and drift away from the main bunch, decay or grow in a step-like manner, before vanishing abruptly. In some cases, sub-packets also concentrate in the central part of the period, forming one or multiple wide clouds that merge or split over time scales of seconds or minutes. Spontaneous transitions between these multiple states occur in a non-periodic manner, so that no quasi-stationary behavior is found over long time scales. These results provide a dramatic illustration of the extremely rich dynamics taking place in fiber lasers at the frontier of mode locking. PMID- 27557174 TI - Chalcogenide optical microwires cladded with fluorine-based CYTOP. AB - We demonstrate optical transmission results of highly nonlinear As2Se3 optical microwires cladded with fluorine-based CYTOP, and compare them with microwires cladded with typical hydrogen-based polymers. In the linear optics regime, the CYTOP-cladded microwire transmits light in the spectral range from 1.3 um up to >2.5 um without trace of absorption peaks such as those observed using hydrogen-based polymer claddings. The microwire is also pumped in the nonlinear optics regime, showing multiple-orders of four-wave mixing and supercontinuum generation spanning from 1.0 um to >4.3 um. We conclude that with such a broadband transparency and high nonlinearity, the As2Se3-CYTOP microwire is an appealing solution for nonlinear optical processing in the mid-infrared. PMID- 27557175 TI - 13.4km OAM state propagation by recirculating fiber loop. AB - Enabled by an enhanced effective index separation (Deltaneff = 1.7 * 10 4) and low transmission loss (0.8dB/km), OAM states are propagated over 13.4km in an air core fiber using a recirculating fiber loop. We observe that intermodal crosstalk decreases rapidly with increasing effective index separation, Deltaneff, and an order of magnitude lower crosstalk may be achieved just by doubling Deltaneff. We find that, in agreement with coupled power theory, our fiber has mode coupling properties analogous to elliptical core PM fibers, which yield ~10 * or more lower crosstalk than for conventional LP fiber mode orders with the same Deltaneff. This confirms that, for OAM modes, birefringent perturbations rather than shape perturbations matter most. In the process of performing the loop experiment, we demonstrate that OAM states in these fibers can be preserved with low loss (<= 0.2dB) and low crosstalk (-15dB) while splicing distinct segments of the air-core fiber. For well-designed fibers, we demonstrate that OAM modes can travel distances relevant for large-scale data centers. PMID- 27557176 TI - Quantification of MDL-induced signal degradation in MIMO-OFDM mode-division multiplexing systems. AB - Mode-division multiplexing (MDM) transmission over few-mode optical fiber has emerged as a promising technology to enhance transmission capacity, in which multiple-input-multiple-output (MIMO) digital signal processing (DSP) after coherent detection is used to demultiplex the signals. Compared with conventional single-mode systems, MIMO-MDM systems suffer non-recoverable signal degradation induced by mode-dependent loss (MDL). In this paper, the MDL-induced signal degradation in orthogonal-frequency-division-multiplexing (OFDM) MDM systems is theoretically quantified in terms of mode-average error vector magnitude (EVM) through frequency domain norm analysis. A novel scalar MDL metric is proposed considering the probability distribution of the practical MDM input signals, and a closed-form expression for EVM measured after zero-force (ZF) MIMO equalization is derived. Simulation results show that the EVM estimations utilizing the novel MDL metric remain unbiased for unrepeated links. For a 6 * 100 km 20-mode MDM transmission system, the estimation accuracy is improved by more than 90% compared with that utilizing traditional condition number (CN) based MDL metric. The proposed MDL metric can be used to predict the MDL-induced SNR penalty in a theoretical manner, which will be beneficial for the design of practical MIMO-MDM systems. PMID- 27557177 TI - Modeling quasi-dark states with temporal coupled-mode theory. AB - Coupled resonators are commonly used to achieve tailored spectral responses and allow novel functionalities in a broad range of applications. The Temporal Coupled-Mode Theory (TCMT) provides a simple and general tool that is widely used to model these devices. Relying on TCMT to model coupled resonators might however be misleading in some circumstances due to the lumped-element nature of the model. In this article, we report an important limitation of TCMT related to the prediction of dark states. Studying a coupled system composed of three microring resonators, we demonstrate that TCMT predicts the existence of a dark state that is in disagreement with experimental observations and with the more general results obtained with the Transfer Matrix Method (TMM) and the Finite-Difference Time-Domain (FDTD) simulations. We identify the limitation in the TCMT model to be related to the mechanism of excitation/decay of the supermodes and we propose a correction that effectively reconciles the model with expected results. Our discussion based on coupled microring resonators can be useful for other electromagnetic resonant systems due to the generality and far-reach of the TCMT formalism. PMID- 27557178 TI - Self-accelerating Airy-Ince-Gaussian and Airy-Helical-Ince-Gaussian light bullets in free space. AB - The evolution of the three-dimensional (3D) self-accelerating Airy-Ince-Gaussian (AiIG) and Airy-Helical-Ince-Gaussian (AiHIG) light bullets is investigated by solving the (3+1)D linear spatiotemporal evolution equation of an optical field analytically. As far as we know, the numerical experimental demonstrations of the Ince-Gaussian (IG) and Helical-Ince-Gaussian (HIG) beams in various modes are first developed to study the evolution characteristics of the different 3D spatiotemporal light bullets. A conclusion can be drawn that the different photoelastics, pulse stacked, boundary, elliptical ring and physically separated in-line vortices can be achieved by adjusting the ellipticity, the evolution distance and the mode-number of light bullets. PMID- 27557179 TI - Generalised optical differentiation wavefront sensor: a sensitive high dynamic range wavefront sensor. AB - Current wavefront sensors for high resolution imaging have either a large dynamic range or a high sensitivity. A new kind of wavefront sensor is developed which can have both: the Generalised Optical Differentiation wavefront sensor. This new wavefront sensor is based on the principles of optical differentiation by amplitude filters. We have extended the theory behind linear optical differentiation and generalised it to nonlinear filters. We used numerical simulations and laboratory experiments to investigate the properties of the generalised wavefront sensor. With this we created a new filter that can decouple the dynamic range from the sensitivity. These properties make it suitable for adaptive optic systems where a large range of phase aberrations have to be measured with high precision. PMID- 27557180 TI - Low cost, high performance white-light fiber-optic hydrophone system with a trackable working point. AB - A working-point trackable fiber-optic hydrophone with high acoustic resolution is proposed and experimentally demonstrated. The sensor is based on a polydimethylsiloxane (PDMS) cavity molded at the end of a single-mode fiber, acting as a low-finesse Fabry-Perot (FP) interferometer. The working point tracking is achieved by using a low cost white-light interferometric system with a simple tunable FP filter. By real-time adjusting the optical path difference of the FP filter, the sensor working point can be kept at its highest sensitivity point. This helps address the sensor working point drift due to hydrostatic pressure, water absorption, and/or temperature changes. It is demonstrated that the sensor system has a high resolution with a minimum detectable acoustic pressure of 148 Pa and superior stability compared to a system using a tunable laser. PMID- 27557181 TI - Efficiently poled electro-optic polymer modulators. AB - A titanium dioxide (TiO2) / electro-optic (EO) polymer hybrid waveguide modulator was designed and fabricated. This modulator possessed a significant advantage for realizing high poling efficiency regardless of the EO polymer resistivity. The in-device EO coefficient was measured to be 100 pm/V, which was 32% higher than that of the thin polymer film. As a result, the phase modulator displayed a VpiL figure of merit of 3.5 V?cm at 1550 nm, which can be reduced further in a push-pull Mach-Zehnder interferometer structure. Temporal stability test of the modulator at 85 degrees C indicated only 8% change of Vpi over 500 hours. The propagation loss in the waveguide was measured as ~3 dB/cm. PMID- 27557182 TI - Local temperature variation measurement by anti-Stokes luminescence in attenuated total reflection geometry. AB - Strong temperature dependence of anti-Stokes luminescence intensity from Rhodamine 101 is used to probe local temperature variation at a surface region in the attenuated total reflection geometry (ATR), when heating with laser light. In this method, the measured region can be limited by observing evanescent luminescence. The near-field depth (penetration depth) was changed by the observation angle thetaout of the evanescent luminescence and the spatial temperature variation was observed. PMID- 27557183 TI - Effective optimization and analysis of white LED properties by using nano honeycomb patterned phosphor film. AB - This study presents an approach for patterning a polydimethylsiloxane (PDMS) phosphor film with a photonic crystal nano-honeycomb structure on a blue chip package. A phosphor film with a nano-honeycomb structure was patterned and transferred using a nanosphere and used for fabricating remote white light emitting diodes (w-LEDs). The angular correlated color temperature deviation of the remote phosphor LED could be improved by varying nano-honeycomb structure pitches (450, 750, and 1150 nm). In particular, w-LED samples with excellent color uniformity (DeltaCCT ranging from 940 to 440 K) were fabricated from 750-nm w-LED samples with nano-honeycomb-patterned tops. PMID- 27557184 TI - Highly linear heterogeneous-integrated Mach-Zehnder interferometer modulators on Si. AB - In this paper we demonstrate highly linear Mach-Zehnder interferometer modulators utilizing heterogeneous integration on a Si substrate (HS-MZM). A record high dynamic range was achieved for silicon devices, obtained using hybrid III-V/Si phase modulation sections and single drive push-pull operation, demonstrating a spurious free dynamic range (SFDR) of 112 dB?Hz2/3 at 10 GHz, comparable to commercial Lithium Niobate MZMs. PMID- 27557185 TI - Engineering non-radiative anapole modes for broadband absorption enhancement of light. AB - In this paper, we propose a novel, frequency- and angularly- broadband approach to achieve absorption rate enhancement in high-index dielectric nanostructures through the engineering of non-radiative anapole modes. We employ multipolar decomposition of numerically computed current distributions and analyze the far field scattering power of multipole moments. By leveraging the destructive interference of electric dipole and toroidal dipole moments, we design non radiating anapole modes and demonstrate significantly enhanced absorbed power in silicon and germanium nanostructures. We demonstrate wide wavelength tunability of the anapole-driven peak absorption enhancement for nano-disks and square nano pixel geometries, which can be conveniently fabricated with current lithography. Finally, by combining nano-disks and nano-pixels of different sizes into functional surface units, we design nanostructured arrays with enhanced bandwidth and absorption rates that can be useful for the engineering of broadband semiconductor photodetectors driven by controllable anapole responses. PMID- 27557186 TI - Gain-guided broad area quantum cascade lasers emitting 23.5 W peak power at room temperature. AB - We report gain-guided broad area quantum cascade lasers at 4.55 MUm. The devices were processed in a buried heterostructure configuration with a current injector section much narrower than the active region. They demonstrate 23.5 W peak power at a temperature of 20 degrees C and duty cycle of 1%, while their far field consists of a single symmetric lobe centered on the optical axis. These experimental results are supported well by 2D numerical simulations of electric currents and optical fields in a device cross-section. PMID- 27557188 TI - Advanced video extensometer for non-contact, real-time, high-accuracy strain measurement. AB - We developed an advanced video extensometer for non-contact, real-time, high accuracy strain measurement in material testing. In the established video extensometer, a "near perfect and ultra-stable" imaging system, combining the idea of active imaging with a high-quality bilateral telecentric lens, is constructed to acquire high-fidelity video images of the test sample surface, which is invariant to ambient lighting changes and small out-of-plane motions occurred between the object surface and image plane. In addition, an efficient and accurate inverse compositional Gauss-Newton algorithm incorporating a temporal initial guess transfer scheme and a high-accuracy interpolation method is employed to achieve real-time, high-accuracy displacement tracking with negligible bias error. Tensile tests of an aluminum sample and a carbon fiber filament sample were performed to demonstrate the efficiency, repeatability and accuracy of the developed advanced video extensometer. The results indicate that longitudinal and transversal strains can be estimated and plotted at a rate of 117 fps and with a maximum strain error less than 30 microstrains. PMID- 27557187 TI - High performance waveguide-coupled Ge-on-Si linear mode avalanche photodiodes. AB - We present experimental results for a selective epitaxially grown Ge-on-Si separate absorption and charge multiplication (SACM) integrated waveguide coupled avalanche photodiode (APD) compatible with our silicon photonics platform. Epitaxially grown Ge-on-Si waveguide-coupled linear mode avalanche photodiodes with varying lateral multiplication regions and different charge implant dimensions are fabricated and their illuminated device characteristics and high speed performance is measured. We report a record gain-bandwidth product of 432 GHz for our highest performing waveguide-coupled avalanche photodiode operating at 1510nm. Bit error rate measurements show operation with BER< 10-12, in the range from -18.3 dBm to -12 dBm received optical power into a 50 Omega load and open eye diagrams with 13 Gbps pseudo-random data at 1550 nm. PMID- 27557189 TI - Quantum-beat based dissipation for spin squeezing and light entanglement. AB - We show an engineered dissipation for the spin squeezing and the light entanglement in a quantum beat system, in which two bright fields interact with an ensemble of three-level atoms in V configuration. The dissipation is based on the atom-field nonlinear interaction that is controlled by the atomic coherence between the excited states off two-photon resonance. Physical analysis and numerical verification are presented for the symmetrical parameters by using the dressed atomic states. It is shown that for particular parameters, the engineered dissipation induces almost perfect two-mode squeezing and entanglement both for the bright fields and for the dressed spins. The excited-state spin has squeezing of near 40% below the standard quantum limit although there remains the spontaneous emission from the involved excited states. PMID- 27557190 TI - High throughput fabrication of large-area plasmonic color filters by soft-X-ray interference lithography. AB - Plasmonic color filters in mass production have been restricted from current fabrication technology, which impede their applications. Soft-X-ray interference lithography (XIL) has recently generated considerable interest as a newly developed technique for the production of periodic nano-structures with resolution theoretically below 4 nm. Here we ameliorate XIL by adding an order sorting aperture and designing the light path properly to achieve perfect stitching nano-patterns and fast fabrication of large-area color filters. The fill factor of nanostructures prepared on ultrathin Ag films can largely affect the transmission minimum of plasmonic color filters. By changing the fill factor, the color can be controlled flexibly, improving the utilization efficiency of the mask in XIL simultaneously. The calculated data agree well with the experimental results. Finally, an underlying mechanism has been uncovered after systematically analyzing the localized surface plasmon polaritons (LSPPs) coupling in electric field distribution. PMID- 27557191 TI - Beam deflection measurement of bound-electronic and rotational nonlinear refraction in molecular gases: erratum. AB - We provide an updated comparison of second hyperpolazability of carbon disulfide reported in [Opt. Express23(17), 22224 (2015)10.1364/OE.23.022224Optica3(6), 657 (2016)10.1364/OPTICA.3.000657]. PMID- 27557192 TI - Phasing piston error in segmented telescopes. AB - To achieve a diffraction-limited imaging, the piston errors between the segments of the segmented primary mirror telescope should be reduced to lambda/40 RMS. We propose a method to detect the piston error by analyzing the intensity distribution on the image plane according to the Fourier optics principle, which can capture segments with the piston errors as large as the coherence length of the input light and reduce these to 0.026lambda RMS (lambda = 633nm). This method is adaptable to any segmented and deployable primary mirror telescope. Experiments have been carried out to validate the feasibility of the method. PMID- 27557193 TI - Numerical studies of focal modulation microscopy in high-NA system. AB - High spatial resolution with deep imaging penetration depth is the main advantage of focal modulation microscopy (FMM). This paper investigates effects of polarization on FMM in a high-NA system based on vectorial diffraction theory. Compared with confocal microscopy, FMM shows a 20.1% improvement in axial resolution. The performance of different polarization patterns is also discussed numerically. The study on polarization modulation may provide a new way to obtain a tighter focal spot. PMID- 27557194 TI - Photo-vibrational spectroscopy of solid and liquid chemicals using laser Doppler vibrometer. AB - Photoacoustic/photothermal spectroscopy is an established technique for trace detection of chemicals and explosives. However, prior sample preparation is required and the analysis is conducted in a sealed space with a high-sensitivity microphone or a piezo sensor coupled with a lock-in amplifier, limiting the technique to applications in a laboratory environment. Due to the aforementioned requirements, traditionally this technique may not be suitable for defense and security applications where the detection of explosives or hazardous chemicals is required in an open environment at a safe standoff distance. In this study, chemicals in various forms (membrane, powder and liquid) were excited by an intensity-modulated quantum cascade laser (QCL), while a laser Doppler vibrometer (LDV) based on the Mach-Zehnder interferometer was applied to detect the vibration signal resulting from the photocoustic/photothermal effect. The photo vibrational spectrum obtained by scanning the QCL's wavelength in MIR range, coincides well with the corresponding spectrum obtained using typical FTIR equipment. The experiment demonstrated that the LDV is a capable sensor for applications in photoacoustic/photothermal spectroscopy, with potential to enable the detection of chemicals in open environment at safe standoff distance. PMID- 27557195 TI - Joint effect of polarization and the propagation path of a light beam on its intrinsic structure. AB - The well-known effects of the spin-orbit interactions of light are manifestations of the pair's mutual influence of the three types of angular momentum (AM) of light, namely, the spin AM, the extrinsic orbital AM and the intrinsic orbital AM. Here we propose a convenient classification of the effects of the spin-orbit interactions of light and we observe one of the new effects in the frame of this classification, which is determined by the joint influence of two types of the AM on the third type of the AM, namely, the influence of the spin AM and the extrinsic orbital AM on the intrinsic orbital AM. We experimentally studied the propagation of circularly polarized light through an optical fiber coiled into a helix. We have found that the spin AM and the helix parameters affect the spatial structure of the radiation transmitted through the optical fiber. We found out that the structure of the light field rotates when changing the sign of circular polarization. The angle of rotation depends on the parameters of the helix. The results can be used to develop the general theory of spinning particles and can find application in metrology methods and nanooptics devices. PMID- 27557196 TI - Dissemination of optical-comb-based ultra-broadband frequency reference through a fiber network. AB - We disseminated an ultra-broadband optical frequency reference based on a femtosecond (fs)-laser optical comb through a kilometer-scale fiber link. Its spectrum ranged from 1160 nm to 2180 nm without additional fs-laser combs at the end of the link. By employing a fiber-induced phase noise cancellation technique, the linewidth and fractional frequency instability attained for all disseminated comb modes were of order 1 Hz and 10-18 in a 5000 s averaging time. The ultra-broad optical frequency reference, for which absolute frequency is traceable to Japan Standard Time, was applied in the frequency stabilization of an injection-seeded Q-switched 2051 nm pulse laser for a coherent light detection and ranging LIDAR system. PMID- 27557197 TI - Holographic projection with higher image quality. AB - The spatial resolution limited by the size of the spatial light modulator (SLM) in the holographic projection can hardly be increased, and speckle noise always appears to induce the degradation of image quality. In this paper, the holographic projection with higher image quality is presented. The spatial resolution of the reconstructed image is 2 times of that of the existing holographic projection, and speckles are suppressed well at the same time. Finally, the effectiveness of the holographic projection is verified in experiments. PMID- 27557198 TI - Emissivity range constraints algorithm for multi-wavelength pyrometer (MWP). AB - In order to realize rapid and real temperature measurement for high temperature targets by multi-wavelength pyrometer (MWP), emissivity range constraints to optimize data processing algorithm without effect from emissivity has been developed. Through exploring the relation between emissivity deviation and true temperature by fitting of large number of data from different emissivity distribution target models, the effective search range of emissivity for every time iteration is obtained, so data processing time is greatly reduced. Simulation and experimental results indicate that calculation time is less by 0.2 seconds with 25K absolute error at 1800K true temperature, and the efficiency is improved by more than 90% compared with the previous algorithm. The method has advantages of simplicity, rapidity, and suitability for in-line high temperature measurement. PMID- 27557199 TI - Moisture-insensitive optical fingerprint scanner based on polarization resolved in-finger scattered light. AB - A moisture-insensitive optical fingerprint scanner (FPS) that is based on polarization resolved in-finger light is proposed and realized. Incident visible light, which is selectively fed to a fingerprint sample via a polarization beam splitter (PBS), is deemed to be partially scattered backward by tissues associated with the skin of the finger. The backscattered light is mostly index guided in the ridge comprising the fingerprint, which has a higher refractive index, and is drastically dispersed in the valley, which is typically filled with water or air and so has a lower index. However, when light reflects directly off the surface of the finger skin, it fundamentally prevents the scanned image from being determined. The proposed FPS produces bright and dark intensity patterns that are alternately created on the surface of the PBS and correspond to the ridges and valleys, respectively. Thus, this method can especially distinguish between a fake synthetic fingerprint and a genuine fingerprint due to its use of in-finger scattered light. The scanner has been rigorously designed by carrying out ray-optic simulations depending on the wavelength, with tissue-induced scattering taken into account. The device was constructed by incorporating a wire grid type PBS in conjunction with visible LED sources, including blue, green and red. The scanner adopting a blue LED, which exhibits the strongest light scattering, resulted in the best fingerprint image, enabling enhanced fidelity under the wet and dry situations. Finally, a fake synthetic fingerprint could be successfully discriminated. PMID- 27557200 TI - Narrow-linewidth Q-switched random distributed feedback fiber laser. AB - A narrow-linewidth Q-switched random fiber laser (RFL) based on a half-opened cavity, which is realized by narrow-linewidth fiber Bragg grating (FBG) and a section of 3 km passive fiber, has been proposed and experimentally investigated. The narrow-linewidth lasing is generated by the spectral filtering of three FBGs with linewidth of 1.21 nm, 0.56 nm, and 0.12 nm, respectively. The Q switching of the distributed cavity is achieved by placing an acousto-optical modulator (AOM) between the FBG and the passive fiber. The maximal output powers of the narrow linewidth RFLs with the three different FBGs are 0.54 W, 0.27 W, and 0.08 W, respectively. Furthermore, the repetition rates of the output pulses are 500 kHz, and the pulse durations are about 500 ns. The corresponding pulse energies are about 1.08 MUJ, 0.54 MUJ, and 0.16 MUJ, accordingly. The linewidth of FBG can influence the output characteristics in full scale. The narrower the FBG, the higher the pump threshold; the lower the output power at the same pump level, the more serious the linewidth broadening; and thus the higher the proportion of the CW-ground exists in the output pulse trains. Thanks to the assistance of the band pass filter (BPF), the proportion of the CW-ground of narrow-linewidth Q-switched RFL under the relative high-pump-low-output condition can be reduced effectively. The experimental results indicate that it is challenging to demonstrate a narrow linewidth Q-switched RFL with high quality output. But further power scaling and linewidth narrowing is possible in the case of operating parameters, optimization efforts, and a more powerful pump source. To the best of our knowledge, this is the first demonstration of narrow-linewidth generation in a Q-switched RFL. PMID- 27557201 TI - Free-space transmission with passive 2D beam steering for multi-gigabit-per second per-beam indoor optical wireless networks. AB - In order to circumvent radio spectrum congestion, we propose an innovative system which can provide multiple infrared optical wireless beams simultaneously where each beam supports multi-gigabit-per-second communication. Scalable two dimensional beam steering by means of wavelength tuning is proposed. A passive beam-steering module constructed with cascaded reflection gratings is designed for simultaneous multi-user coverage. We experimentally characterized the beam steered system and thoroughly evaluated the performance of steered channels using the spectrally efficient and robust discrete multitone modulation in a bandwidth limited system deploying 10 GHz telecom transceivers. This study reports the achievement of at least 37 Gbps free-space transmission per beam over a distance of up to 2 m over 5.61 degrees * 12.66 degrees scanning angles. PMID- 27557202 TI - Ultrabroad linewidth orange-emitting nanowires LED for high CRI laser-based white lighting and gigahertz communications. AB - Group-III-nitride laser diode (LD)-based solid-state lighting device has been demonstrated to be droop-free compared to light-emitting diodes (LEDs), and highly energy-efficient compared to that of the traditional incandescent and fluorescent white light systems. The YAG:Ce3+ phosphor used in LD based solid-state lighting, however, is associated with rapid degradation issue. An alternate phosphor/LD architecture, which is capable of sustaining high temperature, high power density, while still intensity- and bandwidth-tunable for high color-quality remained unexplored. In this paper, we present for the first time, the proof-of-concept of the generation of high-quality white light using an InGaN-based orange nanowires (NWs) LED grown on silicon, in conjunction with a blue LD, and in place of the compound-phosphor. By changing the relative intensities of the ultrabroad linewidth orange and narrow-linewidth blue components, our LED/LD device architecture achieved correlated color temperature (CCT) ranging from 3000 K to above 6000K with color rendering index (CRI) values reaching 83.1, a value unsurpassed by the YAG-phosphor/blue-LD counterpart. The white-light wireless communications was implemented using the blue LD through on off keying (OOK) modulation to obtain a data rate of 1.06 Gbps. We therefore achieved the best of both worlds when orange-emitting NWs LED are utilized as "active-phosphor", while blue LD is used for both color mixing and optical wireless communications. PMID- 27557203 TI - Lasing properties of polymerized chiral nematic Bragg onion microlasers. AB - Dye doped photocurable cholesteric liquid crystal was used to produce solid Bragg onion omnidirectional lasers. The lasers were produced by dispersing and polymerizing chiral nematic LC with parallel surface anchoring of LC molecules at the interface, extracted and transferred into another medium. Lasing characteristics were studied in carrier medium with different refractive index. The lasing in spherical cholesteric liquid crystal was attributed to two mechanisms, photonic bandedge lasing and lasing of whispering-gallery modes. The latter can be suppressed by using a higher index carrier fluid to prevent total internal reflection on the interface of the spheres. Pulse-to-pulse stability and threshold characteristics were also studied and compared to non-polymerized lasers. The polymerization process greatly increases the lasing stability. PMID- 27557204 TI - Invisibility and cloaking structures as weak or strong solutions of Devaney-Wolf theorem. AB - Inspired by a general theorem on non-radiating sources demonstrated by Devaney and Wolf, a unified theory for invisible and cloaking structures is here proposed. By solving Devaney-Wolf theorem in the quasi-static limit, a weak solution is obtained, demonstrating the existence of Anapole modes, Mantle Cloaking and Plasmonic Cloaking. Beyond the quasi-static regime, a strong solution of Devaney-Wolf theorem can be formulated, predicting general non scattering devices based on directional invisibility, Transformation Optics, neutral inclusions and refractive index continuity. Both weak and strong solutions are analytically demonstrated to depend on the concept of contrast, mathematically defined as a normalized difference between constitutive parameters (or wave-impedance property) of a material and its surrounding background. PMID- 27557205 TI - Temperature- and roughness- dependent permittivity of annealed/unannealed gold films. AB - Intrinsic absorption and subsequent heat generation have long been issues for metal-based plasmonics. Recently, thermo-plasmonics, which takes the advantage of such a thermal effect, is emerging as an important branch of plasmonics. However, although significant temperature increase is involved, characterization of metal permittivity at different temperatures and corresponding thermo-derivative are lacking. Here we measure gold permittivity from 300K to 570K, which the latter is enough for gold annealing. More than one order difference in thermo-derivative is revealed between annealed and unannealed films, resulting in a large variation of plasmonic properties. In addition, an unusual increase of imaginary permittivity after annealing is found. Both these effects can be attributed to the increased surface roughness incurred by annealing. Our results are valuable for characterizing extensively used unannealed nanoparticles, or annealed nanostructures, as building blocks in future thermo-nano-plasmonic systems. PMID- 27557206 TI - Strong scintillations of pulsed Laguerrian beams in a turbulent atmosphere. AB - Turbulent fluctuations of the energy density of broadband pulsed Laguerre Gaussian beams are studied based on numerical solution of the parabolic wave equation for the complex spectral amplitude of the wave field by the split-step method. It is shown that in the regime of strong scintillations, the relative variance of energy density of the pulsed beams can take values smaller than unity, in contrast to the strong scintillation index of the continuous-wave beams, which tends to unity with increasing the turbulence strength. The level of residual spatial correlation of the energy density of pulsed beams exceeds that for the continuous-wave beams. It increases with shortening of the pulse duration and increasing of the refractive turbulence strength. PMID- 27557207 TI - Optical vortex generation with wavelength tunability based on an acoustically induced fiber grating. AB - We presented a method to actualize the optical vortex generation with wavelength tunability via an acoustically-induced fiber grating (AIFG) driven by a radio frequency source. The circular polarization fundamental mode could be converted to the first-order optical vortex through the AIFG, and its topological charges were verified by the spiral pattern of coaxial interference between the first order optical vortex and a Gaussian-reference beam. A spectral tuning range from 1540 nm to 1560 nm was demonstrated with a wavelength tunability slope of 4.65 nm/kHz. The mode conversion efficiency was 95% within the whole tuning spectral range. PMID- 27557208 TI - Measurements of the gain medium temperature in an operating Cs DPAL. AB - A Mach-Zehnder interferometer was used for contactless measurement of the temperature of the gain medium within a static cell of Cs DPAL. The maximum temperature recorded approached 700 degrees C leading to a significant degradation of laser performance. This work also examined lasing and non-lasing heat deposition and has shown that as much as 85% of the heating in a DPAL gain medium can be attributed to quenching. PMID- 27557209 TI - Close to transform-limited, few-cycle 12 uJ pulses at 400 kHz for applications in ultrafast spectroscopy. AB - Non-collinear optical parametric amplification has become the leading technology for amplifying few-cycle carrier-envelope phase (CEP) stable pulses to high energy at extreme repetition rates. In this work, a parametric amplifier system devoted to ultrafast photoionization experiments with coincidence detection is reported. The amplifier delivers CEP-stable few-cycle pulses with an average power of 5 W, and operates at repetition rates between 400 and 800 kHz. Close to transform-limited compression of the few-cycle pulses is achieved with minimized spatio-temporal distortions. Potential limitations introduced by spatio-temporal couplings to applications in attosecond science are analyzed. In particular, it is shown that pulse front tilt resulting from non-collinear amplification can considerably reduce the asymmetry in stereo above threshold ionization (stereo ATI) experiments. PMID- 27557210 TI - RF power fading mitigation for an IMDD multicarrier LR-PON. AB - In an intensity-modulation direct-detection (IMDD) orthogonal frequency division multiplexing (OFDM) signal format, radio frequency (RF) power fading produces non uniform receiving performance among the subcarriers due to chromatic dispersion. Hence each subscriber experiences distinct quality of service (QoS) in conventional frequency division multiple access (FDMA). In this paper, a multicarrier code division multiple access (MC-CDMA) signal along with multicode interference (MCI) cancellation process is proposed and experimentally demonstrated to enhance the receiving performance in an IMDD long reach passive optical network (LR-PON). With the proposed scheme, the receiving performance of each subcarrier can be equalized so that a universal transmitter design at central office (CO) can support all the subscribers with their locations ranging from back-to-back to 100 km. Our experimental results also reveal that, even under 20 dB RF power fading, the proposed scheme can still provide over 21.7 dB power budget and only approximately 2 dB sensitivity deviation is observed in an IMDD LR-PON system. PMID- 27557211 TI - All-fiber upconversion high spectral resolution wind lidar using a Fabry-Perot interferometer. AB - An all-fiber, micro-pulse and eye-safe high spectral resolution wind lidar (HSRWL) at 1.5 MUm is proposed and demonstrated by using a pair of upconversion single-photon detectors and a fiber Fabry-Perot scanning interferometer (FFP-SI). In order to improve the optical detection efficiency, both the transmission spectrum and the reflection spectrum of the FFP-SI are used for spectral analyses of the aerosol backscatter and the reference laser pulse. Taking advantages of high signal-to-noise ratio of the detectors and high spectral resolution of the FFP-SI, the center frequencies and the bandwidths of spectra of the aerosol backscatter are obtained simultaneously. Continuous LOS wind observations are carried out on two days at Hefei (31.843 degrees N, 117.265 degrees E), China. The horizontal detection range of 4 km is realized with temporal resolution of 1 minute. The spatial resolution is switched from 30 m to 60 m at distance of 1.8 km. In a comparison experiment, LOS wind measurements from the HSRWL show good agreement with the results from an ultrasonic wind sensor (Vaisala windcap WMT52). An empirical method is adopted to evaluate the precision of the measurements. The standard deviation of the wind speed is 0.76 m/s at 1.8 km. The standard deviation of bandwidth variation is 2.07 MHz at 1.8 km. PMID- 27557212 TI - Single-mode and single-polarization photonics with anchored-membrane waveguides. AB - An integrated photonic platform with "anchored-membrane" structures, the T-Guide, is proposed, numerically investigated, fabricated and characterized. These compact air-clad structures have high index contrast and are much more stable than prior membrane-type structures. Their semi-infinite geometry enables single mode and single-polarization (SMSP) operation over unprecedented bandwidths. Modal simulations quantify this behavior, showing that an SMSP window of 2.75 octaves (1.2-8.1 MUm) is feasible for silicon T-Guides, spanning almost the entire transparency range of silicon. Dispersion engineering for T-Guides yields broad regions of anomalous group velocity dispersion, rendering them a promising platform for nonlinear applications such as wideband frequency conversion. Cut back measurements of fabricated silicon T-guides at lambda = 3.64 MUm show low propagation losses of 1.75 +/- 0.3 dB/cm. PMID- 27557213 TI - Void-nanograting transition by ultrashort laser pulse irradiation in silica glass. AB - The structural evolution from void modification to self-assembled nanogratings in fused silica is observed for moderate (NA > 0.4) focusing conditions. Void formation, appears before the geometrical focus after the initial few pulses and after subsequent irradiation, nanogratings gradually occur at the top of the induced structures. Nonlinear Schrodinger equation based simulations are conducted to simulate the laser fluence, intensity and electron density in the regions of modification. Comparing the experiment with simulations, the voids form due to cavitation in the regions where electron density exceeds 1020 cm-3 but is below critical. In this scenario, the energy absorption is insufficient to reach the critical electron density that was once assumed to occur in the regime of void formation and nanogratings, shedding light on the potential formation mechanism of nanogratings. PMID- 27557214 TI - Estimating the leaf nitrogen content of paddy rice by using the combined reflectance and laser-induced fluorescence spectra. AB - Paddy rice is one of the most important crops in China, and leaf nitrogen content (LNC) serves as a significant indictor for monitoring crop status. A reliable method is needed for precise and fast quantification of LNC. Laser-induced fluorescence (LIF) technology and reflectance spectra of crops are widely used to monitor leaf biochemical content. However, comparison between the fluorescence and reflectance spectra has been rarely investigated in the monitoring of LNC. In this study, the performance of the fluorescence and reflectance spectra for LNC estimation was discussed based on principal component analysis (PCA) and back propagation neural network (BPNN). The combination of fluorescence and reflectance spectra was also proposed to monitor paddy rice LNC. The fluorescence and reflectance spectra exhibited a high degree of multi-collinearity. About 95.38%, and 97.76% of the total variance included in the spectra were efficiently extracted by using the first three PCs in PCA. The BPNN was implemented for LNC prediction based on new variables calculated using PCA. The experimental results demonstrated that the fluorescence spectra (R2 = 0.810, 0.804 for 2014 and 2015, respectively) are superior to the reflectance spectra (R2 = 0.721, 0.671 for 2014 and 2015, respectively) for estimating LNC based on the PCA BPNN model. The proposed combination of fluorescence and reflectance spectra can greatly improve the accuracy of LNC estimation (R2 = 0.912, 0.890 for 2014 and 2015, respectively). PMID- 27557215 TI - Wavelength independent all-fiber angle-tunable polarization rotator based on geometric effects. AB - We propose and demonstrate a simple wavelength independent all-fiber polarization rotator based on purely geometric effects. The device rotates the orientation of an arbitrary input polarization state by arbitrary angle without changing other parameters of the polarization state. The device structure maintains inherent wavelength independence during the tuning process when a non-birefringent single mode fiber is used. PMID- 27557216 TI - Phase and magnitude constrained metasurface holography at W-band frequencies. AB - Holographic optics are an essential tool for the control of light, generating highly complex and tailored light field distributions that can represent physical objects or abstract information. Conceptually, a hologram is a region of space in which an arbitrary phase shift and amplitude variation are added to an incident reference wave at every spatial location, such that the reference wave will produce a desired field distribution as it scatters from the medium. Practical holograms are composed of materials, however, which have limited properties that constrain the possible field distributions. Here, we show it is possible to produce a hologram with continuous phase distribution and a non-uniform amplitude variation at every point by leveraging resonant metamaterial elements and constraining the hologram's pixels to match the elements' resonant behavior. We demonstrate the viability of the resonant metamaterial approach with a single layer, co-polarized holographic metasurface that produces an image at millimeter wavelengths (92.5 GHz) despite the elements' limited phase range and coupled amplitude dependency. PMID- 27557217 TI - Volumetric rendering and metrology of spherical gradient refractive index lens imaged by angular scan optical coherence tomography system. AB - In this paper, we develop the methodology, including the refraction correction, geometrical thickness correction, coordinate transformation, and layer segmentation algorithms, for 3D rendering and metrology of a layered spherical gradient refractive index (S-GRIN) lens based on the imaging data collected by an angular scan optical coherence tomography (OCT) system. The 3D mapping and rendering enables direct 3D visualization and internal defect inspection of the lens. The metrology provides assessment of the surface geometry, the lens thickness, the radii of curvature of the internal layer interfaces, and the misalignment of the internal S-GRIN distribution with respect to the lens surface. The OCT metrology results identify the manufacturing defects, and enable targeted process development for optimizing the manufacturing parameters. The newly fabricated S-GRIN lenses show up to a 7x spherical aberration reduction that allows a significantly increased utilizable effective aperture. PMID- 27557218 TI - Design of Hartmann type null screens for testing a plano-convex aspheric lens with a CCD sensor inside the caustic. AB - A new method to design Hartmann type null screens to test either qualitatively or quantitatively fast plano-convex aspherical lenses is presented. We design both radial and square null screens that produce arrays of circular spots uniformly distributed at predefined planes, considering that the CCD sensor is solely placed inside the caustic region. The designs of these null screens are based on knowledge of the caustic by refraction and on exact ray tracing. The null screens also serve to improve the alignment in optical systems. PMID- 27557219 TI - Statistical properties of radiation of multiwavelength random DFB fiber laser. AB - In the presented paper, the temporal and statistical properties of a Lyot filter based multiwavelength random DFB fiber laser with a wide flat spectrum, consisting of individual lines, were investigated. It was shown that separate spectral lines forming the laser spectrum have mostly Gaussian statistics and so represent stochastic radiation, but at the same time the entire radiation is not fully stochastic. A simple model, taking into account phenomenological correlations of the lines' initial phases was established. Radiation structure in the experiment and simulation proved to be different, demanding interactions between different lines to be described via a NLSE-based model. PMID- 27557220 TI - Enhancement of optical pulse extinction-ratio using the nonlinear Kerr effect for phase-OTDR. AB - We present a novel approach for the generation of high extinction-ratio square pulses based on self-phase modulation of sinusoidally modulated optical signals (SMOS). A SMOS in a nonlinear medium experiences self-phase modulation induced by the nonlinear Kerr effect leading to the generation of distinct sidebands. A small variation in the peak power of the SMOS leads to a large variation in the power of the sidebands. Impressing a square pulse on the SMOS and filtering a sideband component results in a higher extinction-ratio square pulse. The advantage of high extinction-ratio pulses is demonstrated by a reduced background noise level in the Rayleigh backscattering traces of a phase-OTDR vibration measurement system. PMID- 27557221 TI - Mechanism of resonant perfect optical absorption in dielectric film supporting metallic grating structures. AB - The mechanism of resonant perfect optical absorbers is quantitatively revealed by the coupled mode method for the air/grating/dielectric film/air four region system. The sufficient and necessary conditions of the perfect optical absorption are derived from the interface scattering coefficients analyses. The coupling of the Fabry-Perot modes in the grating slits and non-zero order quasi waveguide modes in the dielectric film play a key role for the perfect optical absorption when the light is incident from the grating side. The analytical sufficient and necessary conditions of the perfect optical absorption provide an efficient tool towards geometry design for the perfect optical absorption at the specific wavelengths. The advantages of a widely tunable perfect optical absorption wavelength, a high Q factor and the confined energy loss on metal surfaces make the air/grating/film/air structures promising for applications in sensing, modulation and detection. PMID- 27557222 TI - Thin InSb layers with metallic gratings: a novel platform for spectrally selective THz plasmonic sensing. AB - We present a computational study of terahertz optical properties of a grating coupled plasmonic structure based on micrometer-thin InSb layers. We find two strong absorption resonances that we interpret as standing surface plasmon modes and investigate their dispersion relations, dependence on InSb thickness, and the spatial distribution of the electric field. The observed surface plasmon modes are well described by a simple theory of the air/InSb/air tri-layer. The plasmonic response of the grating/InSb structure is highly sensitive to the dielectric environment and the presence of an analyte (e.g., lactose) at the InSb interface, which is promising for terahertz plasmonic sensor applications. We determine the sensor sensitivity to be 7200 nm per refractive index unit (or 0.06 THz per refractive index unit). The lower surface plasmon mode also exhibits a splitting when tuned in resonance with the vibrational mode of lactose at 1.37 THz. We propose that such interaction between surface plasmon and vibrational modes can be used as the basis for a new sensing modality that allows the detection of terahertz vibrational fingerprints of an analyte. PMID- 27557223 TI - Controllable lasing behavior enabled by compound dielectric waveguide grating structures. AB - The photonic density of states (PDOS) is one of the key physical quantities governing the lasing behavior for photonic band-edge lasers. The PDOS is conventionally altered by exploiting the high-Q band-edge mode within a device, which is typically achieved by increasing the contrast of periodic refractive index variation (Deltan) or increasing the periodic number of the photonic crystals. In this paper, we propose a different approach to achieve a high-Q band edge mode within an active compound dielectric waveguide grating (CWDG). We demonstrate that the lasing threshold and intensity can be flexibly tuned by changing the filling factors of the CWDG. This design can effectively improve the performance of electrically pumped photonic band-edge lasers. PMID- 27557224 TI - Segmented silicon MZM for PAM-8 transmissions at 114 Gb/s with binary signaling. AB - We experimentally demonstrate PAM-8 generation from binary electrical signals driving a silicon multi-electrode Mach-Zehnder modulator acting as an optical digital-to-analog converter. Measured BER in back-to-back configuration is used to evaluate signal quality. We demonstrate 38 GBd PAM-8 transmission below the forward error correction (FEC) threshold using minimum mean square error (MMSE) equalization. The results show that modulators with segmented phase shifters can be advantageously used to eliminate the need for high bandwidth electronic digital-to-analog converters in the generation of multilevel signals. These modulators, that can be designed and fabricated with standard CMOS compatible tools and processes, are of high interest for short range high-speed data links. PMID- 27557226 TI - Transmission loss between single-mode Gaussian antennas. AB - We analytically derive a set of formulas for the transmission loss in vacuum between antennas that send and receive single-mode Gaussian beams. We relate our results to standard far-field link budget parameters. PMID- 27557225 TI - Theoretical study of mode evolution in active long tapered multimode fiber. AB - A concise and effective model based on coupled mode theory to describe mode evolution in long tapered active fiber is presented in this manuscript. The mode coupling due to variation of core radius and slight perturbation have been analyzed and local gain with transverse spatial hole burning (TSHB) effect, loss and curvature have been taken into consideration in our model. On the base of this model, the mode evolution behaviors under different factors have been numerically investigated. Our model and results can provide instructive suggestions when designing long tapered fiber based laser and amplifiers. PMID- 27557227 TI - Optical path length and trajectory stability in rotationally asymmetric multipass cells. AB - We describe the behavior of optical trajectories in multipass rotationally asymmetric cavities (RACs) using a phase-space motivated approach. Emphasis is placed on generating long optical paths. A trajectory with an optical path length of 18 m is generated within a 68 cm3 volume. This path length to volume ratio (26.6 cm-2) is large compared to current state of the art multipass cells such as the cylindrical multipass cell (6.6 cm-2) and astigmatic Herriott cell (9 cm-2). Additionally, the effect of small changes to the input conditions on the path length is studied and compared to the astigmatic Herriott cell. This work simplifies the process of designing RACs with long optical path lengths and could lead to broader implementation of these multipass cells. PMID- 27557228 TI - Temperature-dependent photoluminescence properties of quaternary ZnAgInS quantum dots. AB - A series of ZnAgInS (ZAIS) quantum dots were synthesized and their optical properties were tuned by adjusting the reaction times from 5 to 30 min. The emission spectra were observed ranging from 619 to 667 nm. The temperature dependent photoluminescence properties of ZAIS QDs were investigated from 10 K to 300 K that show a blue shift of spectra line with increasing intensity as well as broadening of spectral line owing to the coupling of the carrier to acoustic phonon. We have also discussed and investigated the internal luminescence mechanism of ZAIS QDs. PMID- 27557229 TI - Grating-coupled Otto configuration for hybridized surface phonon polariton excitation for local refractive index sensitivity enhancement. AB - We demonstrate numerically through rigorous coupled wave analysis (RCWA) that replacing the prism in the Otto configuration with gratings enables us to excite and control different modes and field patterns of surface phonon polaritons (SPhPs) through the incident wavelength and height of the Otto spacing layer. This modified Otto configuration provides us the following multiple modes, namely, SPhP mode, Fabry-Perot (FP) cavity resonance, dielectric waveguide grating resonance (DWGR) and hybridized between different combinations of the above mentioned modes. We show that this modified grating-coupled Otto configuration has a highly confined field pattern within the structure, making it more sensitive to local refractive index changes on the SiC surface. The hybridized surface phonon polariton modes also provide a stronger field enhancement compared to conventional pure mode excitation. PMID- 27557230 TI - Compact three-dimensional head-mounted display system with Savart plate. AB - We propose three-dimensional (3D) head-mounted display (HMD) providing multi focal and wearable functions by using polarization-dependent optical path switching in Savart plate. The multi-focal function is implemented as micro display with high pixel density of 1666 pixels per inches is optically duplicated in longitudinal direction according to the polarization state. The combination of micro display, fast switching polarization rotator and Savart plate retains small form factor suitable for wearable function. The optical aberrations of duplicated panels are investigated by ray tracing according to both wavelength and polarization state. Astigmatism and lateral chromatic aberration of extraordinary wave are compensated by modification of the Savart plate and sub-pixel shifting method, respectively. To verify the feasibility of the proposed system, a prototype of the HMD module for monocular eye is implemented. The module has the compact size of 40 mm by 90 mm by 40 mm and the weight of 131 g with wearable function. The micro display and polarization rotator are synchronized in real time as 30 Hz and two focal planes are formed at 640 and 900 mm away from eye box, respectively. In experiments, the prototype also provides augmented reality function by combining the optically duplicated panels with a beam splitter. The multi-focal function of the optically duplicated panels without astigmatism and color dispersion compensation is verified. When light field optimization for two additive layers is performed, perspective images are observed, and the integration of real world scene and high quality 3D images is confirmed. PMID- 27557231 TI - High efficiency, single-lobe surface-emitting DFB/DBR quantum cascade lasers. AB - We demonstrate a surface-emitting quantum cascade laser (QCL) based on second order buried distributed feedback/distributed Bragg reflector (DFB/DBR) gratings for feedback and outcoupling. The grating fabricated beneath the waveguide was found to fundamentally favor lasing in symmetric mode either through analysis or experiment. Single-lobe far-field radiation pattern with full width at half maximum (FWHM) of 0.18 degrees was obtained along the cavity-length direction. Besides, the buried DFB/DBR grating structure successfully provided an efficient vertical outcoupling mechanism with low optical losses, which manages to achieve a high surface outcouping efficiency of 46% in continuous-wave (CW) operation and 60% in pulsed operation at room temperature. Single-mode emission with a side mode suppression ratio (SMSR) about 25 dB was continuously tunable by heat sink temperature or injection current. Our work contributes to the realization of high efficiency surface-emitting devices with high far-field beam quality that are significantly needed in many application fields. PMID- 27557233 TI - Narrowband cw injection seeded high power femtosecond double-pass optical parametric generator at 43 MHz: Gain and noise dynamics. AB - We demonstrate narrowband cw injection seeding of a femtosecond double-pass optical parametric generator at 43 MHz repetition rate with a simple, low power external cavity diode laser. Up to 2.5 W of near-IR radiation (1.5 - 1.66 um) as well as 800 mW of tunable mid-IR radiation (2.75 - 3.15 um) with pulse durations below 300 fs are generated with a remarkable pulse-to-pulse and long term power stability. Compared to conventional, vacuum noise seeded optical parametric generators, the presented frequency conversion scheme does not only exhibit superior gain and noise dynamics, but also a high degree of flexibility upon control parameters such as pump power, seed power, or spectral position of the seed. PMID- 27557232 TI - Magneto-conductivity and magnetically-controlled nonlinear optical transmittance in multi-wall carbon nanotubes. AB - The impact of vectorial magnetic field effects on electrical conductivity and nonlinear optical transmittance exhibited by multi-wall carbon nanotubes was studied. The samples were synthetized by an aerosol pyrolysis processing route in a thin film form. Optical signals in a two-wave mixing configuration allowed us to identify two orthogonal directions of propagation for a magnetic field travelling through the nanomaterials studied. A selective modification in optical absorption was considered to be induced by magnetic perturbations in the sample. Standard optical Kerr gate measurements were carried out for exploring the third order nonlinear optical behavior of the film. A capacitive effect influenced by optical and magnetic excitations was distinguished to be characteristic of the sample. Magneto-quantum conductivity sensitive to the direction of an external magnetic field interacting with the tubes was analyzed. Magnetically-induced changes in electronic band parameters seem to be the main responsible for the optical and electrical modulation observed in the nanostructures. Immediate applications for developing magneto-optical and magneto-electrical functions can be contemplated. PMID- 27557234 TI - Surface enhanced fluorescence by metallic nano-apertures associated with stair gratings. AB - Metallic nano-apertures associated with stair-gratings are proposed for surface enhanced fluorescence with high excitation enhancement and narrow emission beaming effect. Fluorescence correlation spectroscopy method was utilized to analyze the fluorescence trace and fluorescence enhancement, and the angular patterns of fluorescent emission were measured with the back focal plane imaging method. The stair-grating presents a strong optical response which covering well both the excitation and the emission bands of the photoluminescence process. Such high enhancement and narrow directionality by the stair-gratings would enable the detection of single molecules with low numerical aperture objective effectively. PMID- 27557235 TI - Quantum random number generation enhanced by weak-coherent states interference. AB - We propose and demonstrate a technique for quantum random number generation based on the random population of the output spatial modes of a beam splitter when both inputs are simultaneously fed with indistinguishable weak coherent states. We simulate and experimentally validate the probability of generation of random bits as a function of the average photon number per input, and compare it to the traditional approach of a single weak coherent state transmitted through a beam splitter, showing an improvement of up to 32%. The ensuing interference phenomenon reduces the probability of coincident counts between the detectors associated with bits 0 and 1, thus increasing the probability of occurrence of a valid output. A long bit string is assessed by a standard randomness test suite with good confidence. Our proposal can be easily implemented and opens attractive performance gains without a significant trade-off. PMID- 27557236 TI - Generation of highly stable WDM time-bin entanglement by cascaded sum-frequency generation and spontaneous parametric downconversion in a PPLN waveguide device. AB - In this paper we report the generation of wavelength-division-multiplexed, time bin entangled photon pairs by using cascaded optical second nonlinearities (sum frequency generation and subsequent spontaneous parametric downconversion) in a periodically poled LiNbO3 device. Visibilities of approximately 94% were clearly observed in two-photon interference experiments for all the wavelength-multiplexed channels under investigation (five pairs), with insensitivity to the polarization states of the photon pairs. We also evaluated the performances in terms of quantum-key-distribution (QKD) applications by using four single-photon detectors, which enables to evaluate the QKD performance properly. The results showed long-term stability over 70 hours, maintaining approximately 3% of the quantum error rate and 110 bit/s of the sifted key rate. PMID- 27557237 TI - Photonic-assisted chirped microwave pulses generation with a flexible and fine parameter manipulation. AB - A photonic approach for generating chirped microwave pulses with a flexible and fine parameter manipulation is proposed and experimentally demonstrated. In the proposed system, an intensity modulator (IM) biased at the minimum transmission point is used to generate two +/- 1st-order optical sidebands which are then sent to a phase modulator (PM) for implementing large-signal phase modulations. A de interleaver combined with an optical variable delay line (OVDL) is utilized to introduce a time delay between two phase-modulated optical signals. A second IM that acts as a time domain intensity switch (TDIS) is used to select different phase modulation ranges of the two phase-modulated optical signals. After the optical-electrical conversion in a photodetector (PD), chirped microwave pulses are generated. The key feature of this approach is that the parameters of the generated chirped microwave pulses including central frequency, pulse repetition frequency, and chirp rate can be flexibly and precisely manipulated by the radio frequency (RF) signals applied to modulators. A proof-of-principle experiment is carried out to verify the proposed approach. Consequently, positive or negative chirped microwave pulses with different central frequencies at 20, 22, 24 or 26 GHz and different pulse repetition frequencies at 1.5 or 2 GHz are generated, respectively. PMID- 27557238 TI - Silk fibroin diaphragm-based fiber-tip Fabry-Perot pressure sensor. AB - A miniature fiber-optic Fabry-Perot is built on the tip of a single mode fiber with a thin silk fibroin film as the diaphragm for pressure measurement. The silk fibroin film is regenerated from aqueous silk fibroin solution obtained by an environmentally benign fabrication process, which exhibits excellent optical and physicochemical properties, such as transparency in visible and near infrared region, membrane-forming ability, good adhesion, and high mechanical strength. The resulted Fabry-Perot pressure sensor is therefore highly biocompatible and shows good airtightness with a response of 12.3 nm/kPa in terms of cavity length change. PMID- 27557239 TI - Experimental investigation of the effect of binocular disparity on the visibility threshold of asymmetric noise in stereoscopic viewing. AB - Stereoscopic images could have asymmetric distortions caused by image processing in capture, synthesis, and compression of them. In 3D perception in stereoscopic display, the visibility threshold of the asymmetric distortions in the left and right images is important, which is tolerable to the human visual system. In this paper, we investigate the effect of the binocular disparity on the visibility threshold of asymmetric noises in stereoscopic images via subjective assessments. Existing just-noticeable-difference (JND) models for stereoscopic images have not taken into account the effect of the disparity in stereoscopic viewing. In this paper, we subjectively assessed the visibility threshold of asymmetric noises in stereoscopic images according to the disparity. Subjective evaluations showed that large disparity magnitudes could make more tolerable to perceive the asymmetric noises in the stereoscopic viewing. PMID- 27557240 TI - Domain engineering algorithm for practical and effective photon sources. AB - We introduce a method for shaping the spectral response of nonlinear light sources by tailoring the quasi-phase matching. Our algorithm relies on engineering the poling to accurately trace a generated target signal field amplitude to determine the desired nonlinearity profile. The proposed poling algorithm results in a poling pattern that is more robust to manufacture, as all domain inversions are of equal width. The poling pattern is verified using a nonlinear beam propagation method simulation. This approach is applied to achieve Gaussian-shaped phase matching along a potassium titanyl phosphate (KTP) crystal in order to generate pure heralded single photons of spectral purity ~0.996-this is highly desirable for heralded single photon quantum optics. PMID- 27557241 TI - Four-photon-excited fluorescence resonance energy transfer in an aqueous system from ZnSe:Mn/ZnS quantum dots to hypocrellin A. AB - In this work, we established a fluorescence resonance energy transfer (FRET) system between ZnSe:Mn/ZnS quantum dots and Hypocrellin A (HA, a photosensitizer used for photodynamic therapy of cancer) in aqueous solution, excited by four photon. Here, the QDs are the donors and the HA are the acceptors. The four photon-excited fluorescence resonance energy transfer spectrum was obtained under 1300nm femtosecond laser pluses. The experimental results indicated that the highest efficiency of FRET can reach up to 61.3%. Furthermore, the viability test in cancer cells was further demonstrated for biological applications of FRET system. When FRET occurs the cell killing rate of the cancer cells will reach to 84.8% with the 1mM concentration of HA. Our work demonstrates that while the four photon excited FRET system is promising in both optics and biological applications, is also needs further investigation. PMID- 27557242 TI - Insights into directional scattering: from coupled dipoles to asymmetric dimer nanoantennas. AB - Strong and directionally specific forward scattering from optical nanoantennas is of utmost importance for various applications in the broader context of photovoltaics and integrated light sources. Here, we outline a simple yet powerful design principle to perceive a nanoantenna that provides directional scattering into a higher index substrate based on the interference of multiple electric dipoles. A structural implementation of the electric dipole distribution is possible using plasmonic nanoparticles with a fairly simple geometry, i.e. two coupled rectangular nanoparticles, forming a dimer, on top of a substrate. The key to achieve directionality is to choose a sufficiently large size for the nanoparticles. This promotes the excitation of vertical electric dipole moments due to the bi-anisotropy of the nanoantenna. In turn, asymmetric scattering is obtained by ensuring the appropriate phase relation between the vertical electric dipole moments. The scattering strength and angular spread for an optimized nanoantenna can be shown to be broadband and robust against changes in the incidence angle. The scattering directionality is maintained even for an array configuration of the dimer. It only requires the preferred scattering direction of the isolated nanoantenna not to be prohibited by interference. PMID- 27557243 TI - Long-range measurement of Rayleigh scatter signature beyond laser coherence length based on coherent optical frequency domain reflectometry. AB - Long-range C-OFDR measurement of fiber Rayleigh scatter signature is described. The Rayleigh scatter signature, which is an interference pattern of backscatters from the random refractive indices in fibers, is known to be applicable to fiber identification and temperature or strain sensing by measuring its repeatability and its spectral shift. However, these applications have not been realized at ranges beyond the laser coherence length since laser phase noise degrades its repeatability. This paper proposes and demonstrates a method for analyzing the optical power spectrum of local Rayleigh backscatter to overcome the limitation imposed by laser phase noise. The measurable range and spatial performance are also investigated experimentally with respect to the remaining phase noise and noise reduction by signal averaging with the proposed method. The feasibility of Rayleigh scatter signature measurement for long-range applications is confirmed. PMID- 27557244 TI - Enhanced third harmonic generation in a silicon metasurface using trapped mode. AB - We experimentally demonstrate enhanced third harmonic generation (THG) using a silicon metasurface, which is consist of symmetric spindle-shape nanoparticle array. Relying on the trapped mode supported by the high quality factor all dielectric metasurface, the conversion efficiency of THG is about 300 times larger than that of bulk silicon slab. The maximum extinction ratio of the intensity of THG reaches about 25 dB by tuning the polarization of incident light. The simulation results agree with the experimental performances. PMID- 27557245 TI - Computer-aided high-accuracy testing of reflective surface with reverse Hartmann test. AB - The deflectometry provides a feasible way for surface testing with a high dynamic range, and the calibration is a key issue in the testing. A computer-aided testing method based on reverse Hartmann test, a fringe-illumination deflectometry, is proposed for high-accuracy testing of reflective surfaces. The virtual "null" testing of surface error is achieved based on ray tracing of the modeled test system. Due to the off-axis configuration in the test system, it places ultra-high requirement on the calibration of system geometry. The system modeling error can introduce significant residual systematic error in the testing results, especially in the cases of convex surface and small working distance. A calibration method based on the computer-aided reverse optimization with iterative ray tracing is proposed for the high-accuracy testing of reflective surface. Both the computer simulation and experiments have been carried out to demonstrate the feasibility of the proposed measurement method, and good measurement accuracy has been achieved. The proposed method can achieve the measurement accuracy comparable to the interferometric method, even with the large system geometry calibration error, providing a feasible way to address the uncertainty on the calibration of system geometry. PMID- 27557246 TI - High energy, high repetition rate, second harmonic generation in large aperture DKDP, YCOB, and LBO crystals. AB - We report on type-I phase-matched second harmonic generation (SHG) in three nonlinear crystals: DKDP (98% deuteration), YCOB (XZ plane), and LBO (XY plane), of 8 J, 10 Hz cryogenic gas cooled Yb:YAG laser operating at 1029.5 nm. DKDP exhibited an efficiency of 45% at a peak fundamental intensity of 0.24 GW/cm2 for 10 Hz operation at 10 ns. At the same intensity and repetition rate, YCOB and LBO showed 50% and 65% conversion efficiencies, respectively. Significant improvement in conversion efficiency, to a maximum of 82%, was demonstrated in LBO at 0.7 GW/cm2 and 10 Hz, generating output energy of 5.6 J at 514.75 nm, without damage or degradation. However, no improvement in conversion efficiency was recorded for YCOB at this increased intensity. Additionally, we present theoretically calculated temperature maps for both 10 J and 100 J operation at 10 Hz, and discuss the suitability of these three crystals for frequency conversion of a 100 J, 10 Hz diode pumped solid state laser (DPSSL). PMID- 27557247 TI - Radial phased-locked partially coherent flat-topped vortex beam array in non Kolmogorov medium. AB - The analytical expressions for the cross-spectral density, the average intensity and the complex degree of spatial coherence of a radial phased-locked partially coherent flat-topped vortex beam array propagating through non-Kolmogorov medium are obtained by using the extended Huygens-Fresnel principle. The evolution behaviors of a radial phased-locked partially coherent flat-topped vortex beam array propagating through non-Kolmogorov medium are studied in detail. It is shown that the evolution behaviors of average intensity depend on beam parameters including the spatial correlation length, the radius of the beam array, as well as the propagation distance. A radial phased-locked partially coherent flat topped vortex beam array with high coherence evolves more rapidly than that with low coherence. PMID- 27557248 TI - Characterizing the radial content of orbital-angular-momentum photonic states impaired by weak-to-strong atmospheric turbulence. AB - The changes in the radial content of orbital-angular-momentum (OAM) photonic states described by Laguerre-Gaussian (LG) modes with a radial index of zero, suffering from turbulence-induced distortions, are explored by numerical simulations. For a single-photon field with a given LG mode propagating through weak-to-strong atmospheric turbulence, both the average LG and OAM mode densities are dependent only on two nondimensional parameters, i.e., the Fresnel ratio and coherence-width-to-beam-radius (CWBR) ratio. It is found that atmospheric turbulence causes the radially-adjacent-mode mixing, besides the azimuthally adjacent-mode mixing, in the propagated photonic states; the former is relatively slighter than the latter. With the same Fresnel ratio, the probabilities that a photon can be found in the zero-index radial mode of intended OAM states in terms of the relative turbulence strength behave very similarly; a smaller Fresnel ratio leads to a slower decrease in the probabilities as the relative turbulence strength increases. A photon can be found in various radial modes with approximately equal probability when the relative turbulence strength turns great enough. The use of a single-mode fiber in OAM measurements can result in photon loss and hence alter the observed transition probability between various OAM states. The bit error probability in OAM-based free-space optical communication systems that transmit photonic modes belonging to the same orthogonal LG basis may depend on what digit is sent. PMID- 27557249 TI - Optimization of beam transformation system for laser-diode bars. AB - An optimized beam transformation system (BTS) is proposed to improve the beam quality of laser-diode bars. Through this optimized design, the deterioration of beam quality after the BTS can be significantly reduced. Both the simulation and experimental results demonstrate that the optimized system enables the beam quality of a mini-bar (9 emitters) approximately equal to 5.0 mm * 3.6 mrad in the fast-axis and slow-axis. After beam shaping by the optimized BTS, the laser diode beam can be coupled into a 100 MUm core, 0.15 numerical aperture (NA) fiber with an output power of over 100 W and an electric-optical efficiency of 46.8%. PMID- 27557250 TI - Interference effects on harmonic generation from H2 + in nonhomogeneous laser field. AB - By solving the time-dependent Schrodinger equation both in simplified one dimensional coordinate and three-dimensional cylindrical coordinate systems, the high-order harmonic generation from H2 + in spatially symmetric and asymmetric nonhomogeneous laser fields was studied. At large internuclear distances, minima were clearly observed in high energy part of harmonic spectra, which can be attributed to two-center interference in diatomic molecule. Compared with previous studies, the minima in nonhomogeneous laser field are more distinct. Remarkably, the positions of the minima are different in these two types of fields, which demonstrate that interference effects are greatly influenced by laser parameters. Besides, the asymmetric nonhomogeneous field leads to an asymmetric recollision of the ionized electron, and both odd and even order harmonics could be emitted, which is explained in detail based on quantum dynamics calculations. PMID- 27557251 TI - Laser differential confocal ultra-large radius measurement for convex spherical surface. AB - A new laser differential confocal ultra-large radius measurement (LDCRM) method is proposed for high-precision measurement of ultra-large radii. Based on the property that the zero point of a differential confocal axial intensity curve precisely corresponds to the focus points of focusing beam, LDCRM measures the vertex positions of the test lens and the last optical surface of objective lens to obtain position difference L1, and then measures the vertex positions of the reflector and the last optical surface of objective lens to obtain the position difference L2, finally uses the measured L1 and L2 to calculate the radius of test lens. This method does not require the identification of confocal position. Preliminary experimental results and theoretical analyses indicate that the relative uncertainty is 0.03% for a convex spherical lens with a radius of approximately 20 m. LDCRM provides a novel approach for high-precision ultra-large radius measurement. PMID- 27557252 TI - Widely tunable single-/dual-wavelength fiber lasers with ultra-narrow linewidth and high OSNR using high quality passive subring cavity and novel tuning method. AB - High stability single- and dual-wavelength compound cavity erbium-doped fiber lasers (EDFLs) with ultra-narrow linewidth, high optical signal to noise ratio (OSNR) and widely tunable range are demonstrated. Different from using traditional cascaded Type-1/Type-2 fiber rings as secondary cavities, we nest a Type-1 ring inside a Type-2 ring to form a passive subring cavity to achieve single-longitudinal-mode (SLM) lasing with ultra-narrow linewidth for the first time. We also show that the SLM lasing stability can be further improved by inserting a length of polarization maintaining fiber in the Type-2 ring. Using a uniform fiber Bragg grating (FBG) and two superimposed FBGs as mode restricting elements, respectively, we obtain a single-wavelength EDFL with a linewidth as narrow as 715 Hz and an OSNR as high as 73 dB, and a dual-wavelength EDFL with linewidths less than 1 kHz and OSNRs higher than 68 dB for both lasing wavelengths. Finally, by employing a novel self-designed strain adjustment device capable of applying both the compression and tension forces to the FBGs for wavelength tuning, we achieve the tuning range larger than 10 nm for both of the EDFLs. PMID- 27557253 TI - Single-frequency tunable 447.3 nm laser by frequency doubling of tapered amplified diode laser at cesium D1 line. AB - A continuous single-frequency tunable blue laser at 447.3 nm is developed by external-cavity frequency doubling of a tapered amplifier-boosted continuous-wave diode laser at cesium (Cs) D1 line. A maximum blue power of 178 mW with 50.8% conversion efficiency is obtained. It can be continuously tuned over a range around 1.6 GHz as the diode laser frequency is scanned across the F=4 >F'=3 transition of 133Cs D1 line. The generated tunable and stable blue laser source has potential applications in constructing quantum light-atom interfaces in quantum networks. PMID- 27557254 TI - Directional generation of graphene plasmons by near field interference. AB - The highly unidirectional excitation of graphene plasmons (GPs) through near field interference of orthogonally polarized dipoles is investigated. The preferred excitation direction of GPs by a circularly polarized dipole can be simply understood with the angular momentum conservation law. Moreover, the propagation direction of GPs can be switched not only by changing the phase difference between dipoles, but also by placing the z-polarized dipole to its image position, whereas the handedness of the background field remains the same. The unidirectional excitation of GPs can be extended into arc graphene surface as well. Furthermore, our proposal on directional generation of GPs can be realized in a semiconductor nanowire/graphene system, where a semiconductor nanowire can mimic a circularly polarized dipole when illuminated by two orthogonally polarized plane waves. PMID- 27557255 TI - Optimal illumination for visual enhancement based on color entropy evaluation. AB - Object visualization is influenced by the spectral distribution of an illuminant impinging upon it. In this paper, we proposed a color entropy evaluation method to provide the optimal illumination that best helps surgeons distinguish tissue features. The target-specific optimal illumination was obtained by maximizing the color entropy value of our sample tissue, whose spectral reflectance was measured using multispectral imaging. Sample images captured under optimal light were compared with that under commercial white light emitting diodes (3000K, 4000K and 5500K). Results showed images under the optimized illuminant had better visual performance such as more subtle details exhibited. PMID- 27557256 TI - Calculation of reflectance distribution using angular spectrum convolution in mesh-based computer generated hologram. AB - We propose a method to obtain a computer-generated hologram that renders reflectance distributions of individual mesh surfaces of three-dimensional objects. Unlike previous methods which find phase distribution inside each mesh, the proposed method performs convolution of angular spectrum of the mesh to obtain desired reflectance distribution. Manipulation in the angular spectrum domain enables its application to fully-analytic mesh based computer generated hologram, removing the necessity for resampling of the spatial frequency grid. It is also computationally inexpensive as the convolution can be performed efficiently using Fourier transform. In this paper, we present principle, error analysis, simulation, and experimental verification results of the proposed method. PMID- 27557257 TI - Micrometer-resolution in-fiber OCT probe with tunable working distance. AB - Optical coherence tomography (OCT) is an attractive modality in biomedical imaging systems due to its non-invasive imaging character. Since the image quality of OCT may be limited by the decrease of transverse resolution away from the focus spot, working distance tunable probe can be a strategy to overcome such limitation and maintain high transverse resolution at different imaging depths. In this paper, a miniature, working distance-tunable in-fiber OCT probe is demonstrated. The influences of the graded index fiber (GIF) length as well as the air cavity length on the working distance and the transverse resolution are simulated and discussed. Experimental results prove that the working distance can be tuned freely from 337.31 MUm to 22.28 MUm, producing the transverse resolution from 13.86 MUm to 3.6 MUm, which are in good agreement with the simulated results. The application of the probe in an OCT system for imagining a standard USAF resolution target is investigated in detail. The best resolutions for the standard USAF resolution target imaging are 4.9 MUm and 6.9 MUm in horizontal and vertical direction, respectively. PMID- 27557258 TI - Spectroscopic and laser properties of bulk iron doped zinc magnesium selenide Fe:ZnMgSe generating at 4.5 - 5.1 um. AB - The Fe:Zn(1-x)Mg(x)Se (x = 0.19, 0.27, and 0.38) solid solutions spectroscopic properties were investigated and laser oscillations were achieved for the first time. The increase of the magnesium concentration in the Fe:ZnMgSe crystal was shown to result in an almost similar long wavelength shift of both absorption and fluorescence spectra of about 60 nm per each 10% of magnesium. With the Fe:ZnMgSe crystal temperature decrease, the fluorescence spectrum maximum shifts towards shorter wavelength resulting mainly from strong narrowing of the longest wavelength fluorescence line. Laser radiation wavelength dependence on the magnesium concentration as well as on temperature was observed. The Fe:ZnMgSe x = 0.38 laser oscillation wavelength increased from 4780 nm at 80 K to 4920 nm at 240 K using the optical resonator without any intracavity spectrally-selective element. In comparison with the Fe:ZnSe laser operating in similar conditions, these wavelengths at both temperatures were shifted by about 500 nm towards mid IR region. PMID- 27557259 TI - High dispersive mirrors for erbium-doped fiber chirped pulse amplification system. AB - We report on the development of near-infrared high dispersive mirrors (HDM) with a group delay dispersion (GDD) of -2000 fs2. A HDM pair based on one optimized result at two reference wavelengths (1550 nm and 1560 nm) can reduce the total oscillation of the GDD effectively in the wavelength range of 1530-1575 nm. This HDM pair is designed and fabricated in a single coating run by means of the nonuniformity in film deposition. For the first time, near-infrared HDMs with two different reference wavelengths have been successfully applied in an erbium doped fiber chirped pulse amplification system for the compression of 4.73 ps laser pulses to 380 fs. PMID- 27557260 TI - Thermal lensing in optical fibers. AB - Average powers from fiber lasers have reached the point that a quantitative understanding of thermal lensing and its impact on transverse mode instability is becoming critical. Although thermal lensing is well known qualitatively, there is a general lack of a simple method for quantitative analysis. In this work, we first conduct a study of thermal lensing in optical fibers based on a perturbation technique. The perturbation technique becomes increasingly inaccurate as thermal lensing gets stronger. It, however, provides a basis for determining a normalization factor to use in a more accurate numerical study. A simple thermal lensing threshold condition is developed. The impact of thermal lensing on transverse mode instability is also studied. PMID- 27557262 TI - Frequency comb SFG: a new approach to multiplex detection. AB - Determination of molecular orientation at interfaces by vibrational sum frequency generation spectroscopy (VSFG) requires measurements using at least two different polarization combinations of the incoming visible, IR, and generated SFG beams. We present a new method for the simultaneous collection of different VSFG polarization outputs by use of a modified 4f pulseshaper to create a simple frequency comb. Via the frequency comb, two visible pulses are separated spectrally but aligned in space and time to interact at the sample with mixed polarization IR light. This produces two different VSFG outputs that are separated by their frequencies at the monochromator rather than their polarizations. Spectra were collected from organic thin films with different polarization combinations to show the reliability of the method. The results show that the optical arrangement is immune to fluctuations in laser power, beam pointing, and IR spectral shape. PMID- 27557263 TI - Effect of input phase modulation to a phase-sensitive optical amplifier. AB - Many optical applications depend on amplitude modulating optical beams using devices such as acousto-optical modulators (AOMs) or optical choppers. Methods to add amplitude modulation (AM) often inadvertently impart phase modulation (PM) onto the light as well. While this PM is of no consequence to many phase insensitive applications, phase-sensitive processes can be affected. Here we study the effects of input phase and amplitude modulation on the output of a quantum-noise limited phase-sensitive optical amplifier (PSA) realized in hot 85Rb vapor. We investigate the dependence of PM on AOM alignment and demonstrate a novel approach to quantifying PM by using the PSA as a diagnostic tool. We then use this method to measure the alignment-dependent PM of an optical chopper which arises due to diffraction effects as the chopper blade passes through the optical beam. PMID- 27557261 TI - Characterizing cellular morphology by photoacoustic spectrum analysis with an ultra-broadband optical ultrasonic detector. AB - Photoacoustic spectrum analysis (PASA) has been demonstrated as a new method for quantitative tissue imaging and characterization. The ability of PASA in evaluating micro-size tissue features was limited by the bandwidth of detectors for photoacoustic (PA) signal acquisition. We improve upon such a limit, and report on developments of PASA facilitated by an optical ultrasonic detector based on micro-ring resonator. The detector's broad and flat frequency response significantly improves the performance of PASA and extents its characterization capability from the tissue level to cellular level. The performance of the system in characterizing cellular level (a few microns) stochastic objects was first shown via a study on size-controlled optically absorbing phantoms. As a further demonstration of PASA's potential clinical application, it was employed to characterize the morphological changes of red blood cells (RBCs) from a biconcave shape to a spherical shape as a result of aging. This work demonstrates that PASA equipped with the micro-ring ultrasonic detectors is an effective technique in characterizing cellular-level micro-features of biological samples. PMID- 27557264 TI - Bistatic laser polarimeter calibrated to 1% at visible-SWIR wavelengths. AB - This paper documents the accuracy and precision of the U. S. Air Force Research Laboratory APCL laser polarimeter in arbitrary bistatic geometries at the three laser wavelengths 633nm, 1064nm, and 1550nm. The difference between measured and theoretical-truth Mueller matrices of calibration components is used as the calibration metric and justified relative to block ellipsometer calibration methods. Calibration of the polarimeter ellipsometry mode is demonstrated first, at quasi-monostatic and large bistatic angles, employing a metallic mirror and a dielectric window as the calibration component, respectively, the latter in order to avoid uncertainty in the retardance of typical metallic mirrors at large incident angles. This uncertainty is demonstrated in measurements of COTS protected-silver mirrors from two vendors, revealing an approximately lambda/8 retardance difference, for reflection through 90 degrees , between nominally identical mirrors from the two vendors. Polarimeter calibration is finally extended beyond ellipsometry by calibrating depolarization measurements using a new technique employing ensembles of polarized states as calibration components. PMID- 27557265 TI - Boosting figures of merit of cavity plasmon resonance based refractive index sensing in dielectric-metal core-shell resonators. AB - We theoretically investigate the sensing performance of the dielectric-metal core shell resonators (DMCSRs) that support multipolar sharp magnetic and electric based cavity plasmon resonances. We show that at the cavity resonances the ability of the DMCSRs to strongly confine the optical fields inside the cavity is robust against the existence of nano-openings in the metal shell layer. As a result, both the perfect DMCSRs having a complete metal shell layer and the non perfect DMCSRs with nano-openings in the metal shell layers exhibit high refractive index sensitivities of 700 ~1200 nm/RIU. Furthermore, we demonstrate that such high refractive index sensitivities could be well maintained in an array of interconnected non-perfect DMCSRs. The narrow linewidths of the cavity plasmon resonances coupled with their high index sensitivities make the array of non-perfect DMCSRs possess high figure of merit (FOM) values up to ~88, approaching the theoretically estimated upper limit (FOM ~108) for gold standard prism coupled surface-plasmon sensors. PMID- 27557266 TI - Spectral super-resolution reflectance retrieval from remotely sensed imaging spectrometer data. AB - Existing atmospheric correction methods retrieve surface reflectance keeping the same nominal spectral response functions (SRFs) as that of the airborne/spaceborne imaging spectrometer radiance data. Since the SRFs vary dependent on sensor type and configuration, the retrieved reflectance of the same ground object varies from sensor to sensor as well. This imposes evident limitations on data validation efforts between sensors at surface reflectance level. We propose a method to retrieve super-resolution reflectance at the surface, by combining the first-principles atmospheric correction method FLAASH (fast line-of-sight atmospheric analysis of spectral hypercubes) with spectral super-resolution of imaging spectrometer radiance data. This approach is validated by comparing airborne AVIRIS (airborne visible/infrared imaging spectrometer) and spaceborne Hyperion data. The results demonstrate that the super-resolution reflectance in spectral bands with sufficiently high signal-to noise ratio (SNR) serves as intermediate quantity to cross validate data originating from different imaging spectrometers. PMID- 27557267 TI - High-dynamic-range fluorescence molecular tomography for imaging of fluorescent targets with large concentration differences. AB - When CCD-based free-space fluorescence molecular tomography (FMT) is used for imaging of fluorescent targets with a large concentration difference, the limited dynamic range of the CCD diminishes the localization and quantitative accuracy of FMT. To overcome this, we present a high-dynamic-range FMT (HDR-FMT) method. Under the multiple-exposure scheme, HDR fluorescence projection images are constructed using the recovered CCD response curve. Image reconstruction is implemented using iterative reweighted L1 regularization which can reduce artifacts by using fewer HDR fluorescence projection images. Phantom and in vivo animal studies indicate that localization of fluorescent targets with a large concentration difference is effectively improved with HDR-FMT and with good quantitative accuracy. PMID- 27557268 TI - Single layer retarder with negative dispersion of birefringence and wide field-of view. AB - A single layer retarder possessing negative dispersion (ND) of birefringence as well as wide field-of-view (FOV) was long-term objective in optical science. We synthesized new guest reactive monomers with x-shape and mixed them with the host smectic reactive mesogen. The host-guest molecules formed two dimensionally self organized nanostructure and showed both the ND of birefringence and wide FOV properties. We simulated the antireflection property of a circular polarizer using the optical properties of the retarder. The average reflectance of the retarder was 0.52% which was much smaller than that of the commercial single layer ND retarder 1.83%. PMID- 27557269 TI - 933 W Yb-doped fiber ASE amplifier with 50.4 nm bandwidth. AB - In this paper, a 933 W amplified spontaneous emission (ASE) source with a full width at half maximum (FWHM) of 50.4 nm is presented. The broadband source is generated by a 1271 W ASE amplifier together with 140m ordinary passive fiber for nonlinear transformation. With multi-wavelength rate equations and a nonlinear Schrodinger equation (NLSE), spectral evolution of the ASE source is analyzed theoretically. PMID- 27557270 TI - Four-plate piezoelectric actuator driving a large-diameter special optical fiber for nonlinear optical microendoscopy. AB - In nonlinear optical microendoscope (NOME), a fiber with excellent optical characteristics and a miniature scanning mechanism at the distal end are two key components. Double-clad fibers (DCFs) and double-clad photonic crystal fibers (DCPCFs) have shown great optical characteristics but limited vibration amplitude due to large diameter. Besides reducing the damping of fiber cantilever, optimizing the structural of the actuator for lower energy dissipation also contributes to better driving capability. This paper presented an optimized actuator for driving a particular fiber cantilever in the view point of energy. Firstly, deformation energy of a bending fiber cantilever operating in resonant mode is investigated. Secondly, strain and stress analyses revealed that the four plate actuator achieved lower energy dissipation. Then, finite-element simulations showed that the large-diameter fiber yielded an adequate vibration amplitude driven by a four-plate actuator, which was confirmed by experiments of our home-made four-plate actuator prototypes. Additionally, a NOME based on a DCPCF with a diameter of 350 MUm driven by four-plate piezoelectric actuator has been developed. The NOME can excite and collect intrinsic second-harmonic and two photon fluorescence signals with the excitation power of 10-30 mW and an adequate field of view of 200 MUm, which suggest great potential applications in neuroscience and clinical diagnoses. PMID- 27557271 TI - High energy, 1572.3 nm pulses for CO2 LIDAR from a polarization maintaining, very-large-mode-area, Er-doped fiber amplifier. AB - We demonstrate the first polarization-maintaining, very-large-mode-area, Er-doped fiber amplifier with ~1100 MUm2 effective area. The amplifier is core pumped by a Raman fiber laser and is used to generate single-frequency, one microsecond, pulses with pulse energy of 541 MUJ, peak power of 700 W, M2 of 1.1, and polarization extinction > 20 dB. The amplifier operates at 1572.3 nm, a wavelength useful for trace atmospheric CO2 detection. PMID- 27557272 TI - Efficient joint timing and frequency synchronization algorithm for coherent optical OFDM systems. AB - A joint timing and frequency synchronization algorithm is proposed for coherent optical orthogonal frequency-division multiplexing (CO-OFDM) systems. The timing and frequency synchronization is realized by using only one training symbol which is composed of conjugated symmetric sequence. The timing estimation of the proposed algorithm has the advantage of being robust to poor optical signal-to noise ratio (OSNR) and chromatic dispersion (CD), and the frequency estimation range of fractional subcarrier spacing can be achieved. The feasibility and effectiveness of the proposed joint synchronization algorithm is verified in both simulations and a 47.3 Gbit/s 16-ary quadrature amplitude modulation (16-QAM) CO OFDM system. PMID- 27557273 TI - Color-conversion efficiency enhancement of quantum dots via selective area nano rods light-emitting diodes. AB - A large enhancement of color-conversion efficiency of colloidal quantum dots in light-emitting diodes (LEDs) with novel structures of nanorods embedded in microholes has been demonstrated. Via the integration of nano-imprint and photolithography technologies, nanorods structures can be fabricated at specific locations, generating functional nanostructured LEDs for high-efficiency performance. With the novel structured LED, the color-conversion efficiency of the existing quantum dots can be enhanced by up to 32.4%. The underlying mechanisms can be attributed to the enhanced light extraction and non-radiative energy transfer, characterized by conducting a series of electroluminescence and time-resolved photoluminescence measurements. This hybrid nanostructured device therefore exhibits a great potential for the application of multi-color lighting sources. PMID- 27557274 TI - Single photon transport in two waveguides chirally coupled by a quantum emitter. AB - We investigate single photon transport in two waveguides coupled to a two-level quantum emitter (QE). With the deduced analytical scattering amplitudes, we show that under condition of the chiral coupling between the QE and the photon in the two waveguides, the QE can play the role of ideal quantum router to redirect a single photon incident from one waveguide into the other waveguide with a probability of 100% in the ideal condition. The influences of cross coupling between two waveguides and dissipations on the routing are also shown. PMID- 27557275 TI - Shared decision making and the pathways approach in the prenatal and postnatal management of the trisomy 13 and trisomy 18 syndromes. AB - The medical management of infants with the trisomy 13 and trisomy 18 syndromes is challenging and controversial. Both conditions have high neonatal and infant mortality, and surviving children display significant cognitive and motor disabilities. Currently, there exists a tension in the neonatal and perinatal communities regarding care. One view holds that management should consist solely of comfort care, while another opinion recommends offering medical and surgical intervention in appropriate situations. The purpose of this manuscript is to present a model for the care of fetuses and infants with trisomy 13 and 18 during the prenatal, perinatal, and postnatal periods. Adopting the pathways approach as a framework, we have identified several pertinent decision points, characterizing the goals of care and the resources needed for the decision points at various times. Additionally, we identified themes surrounding parental and professional experiences. The authors propose a care model for trisomy 13 and 18 that uses shared decision making as its foundational principle and the pathways approach as the method. Our model requires further investigation as a strategy for care in order to render it useful in other complex medical situations. (c) 2016 Wiley Periodicals, Inc. PMID- 27557276 TI - Demonstration of Resonance Coupling in Scalable Dielectric Microresonator Coatings for Photovoltaics. AB - To increase the power conversion efficiency of solar cells, improved antireflection coatings are needed to couple light into the cell with minimal parasitic loss. Here, we present measurements and simulations of an antireflection coating based on silicon dioxide (SiO2) nanospheres that improve solar cell absorption by coupling light from free space into the absorbing layer through excitation of modes within the nanospheres. The deposited monolayer of nanospheres leads to a significant increase in light absorption within an underlying semiconductor on the order of 15-20%. When the periodicity and spacing between the nanospheres are varied, whispering gallery-like modes can be excited and tuned throughout the visible spectrum. The coating was applied to a Si solar cell containing a Si3N4 antireflection layer, and an additional increase in the spectral current density of ~5% was found. The fabrication process, involving Meyer rod rolling, is scalable and inexpensive and could enable large-scale manufacturability of microresonator-based photovoltaics. PMID- 27557277 TI - Using Qualitative and Quantitative Methods to Choose a Habitat Quality Metric for Air Pollution Policy Evaluation. AB - Atmospheric nitrogen (N) deposition has had detrimental effects on species composition in a range of sensitive habitats, although N deposition can also increase agricultural productivity and carbon storage, and favours a few species considered of importance for conservation. Conservation targets are multiple, and increasingly incorporate services derived from nature as well as concepts of intrinsic value. Priorities vary. How then should changes in a set of species caused by drivers such as N deposition be assessed? We used a novel combination of qualitative semi-structured interviews and quantitative ranking to elucidate the views of conservation professionals specialising in grasslands, heathlands and mires. Although conservation management goals are varied, terrestrial habitat quality is mainly assessed by these specialists on the basis of plant species, since these are readily observed. The presence and abundance of plant species that are scarce, or have important functional roles, emerged as important criteria for judging overall habitat quality. However, species defined as 'positive indicator-species' (not particularly scarce, but distinctive for the habitat) were considered particularly important. Scarce species are by definition not always found, and the presence of functionally important species is not a sufficient indicator of site quality. Habitat quality as assessed by the key informants was rank-correlated with the number of positive indicator-species present at a site for seven of the nine habitat classes assessed. Other metrics such as species-richness or a metric of scarcity were inconsistently or not correlated with the specialists' assessments. We recommend that metrics of habitat quality used to assess N pollution impacts are based on the occurrence of, or habitat-suitability for, distinctive species. Metrics of this type are likely to be widely applicable for assessing habitat change in response to different drivers. The novel combined qualitative and quantitative approach taken to elucidate the priorities of conservation professionals could be usefully applied in other contexts. PMID- 27557278 TI - Association between rs17095355 polymorphism on 10q24 and susceptibility to biliary atresia: a meta-analysis. AB - OBJECTIVE: Recent studies have identified 10q24-rs17095355 as a susceptibility locus for biliary atresia (BA). To more precisely estimate the association between the rs17095355 polymorphism and BA risk, a meta-analysis was performed. METHODS: A comprehensive search was conducted to examine all the eligible studies by electronic databases including Elsevier Science Direct, Pubmed, Google Scholar, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature (CBM) up to December 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association. RESULTS: A total of 6 comparisons from 5 relevant studies involving 1000 patients and 3257 controls were included to analyze the association between rs17095355 and BA risk. The pooled OR for T allele of rs17095355 was 1.72 (95%CI 1.53-1.92, p < 0.01) in BA. Stratification by ethnicity indicated the degree of risk of rs17095355 with BA susceptibility was similar in populations of Asian origin. The pooled OR was 1.81 (95%CI 1.60-2.06, p < 0.01). CONCLUSIONS: This meta-analysis confirms the association of rs17095355 polymorphism and BA development, especially in Asians. More original studies with large sample are needed to replicate this genetic association in different ethnic groups. PMID- 27557279 TI - The influence of isometric preload on power expressed during bench press in strength-trained men. AB - The purpose of this study was to compare the power expressed during the bench press exercise in resistance-trained men following different pre-activation conditions. Twenty-two trained men (age 24.1 +/- 1.7 years, height 178.6 +/- 6.1 cm, body mass 81.1 +/- 10.6 kg) completed a maximal effort bench press (1-RM) test (100.0 kg +/- 8.1 kg). In a subsequent assessment, each participant performed concentric bench press movements with loads of 20%, 30%, 40% and 50% of their 1-RM preceded by either a concentric contraction (CC), a low isometric preload (LIP; 70% 1-RM) or a high isometric preload (HIP; 100% 1-RM) conditions. All movements were performed in a Smith machine with a settable quick-release device. Participants performed all three conditions in randomized fashion. Results indicated that power outputs during the bench press exercise following HIP were significantly (p < 0.05) greater than CC at 20% 1-RM (+9%), 30% 1-RM (+16%) and 40% 1-RM (+14%), and LIP at 20% 1-RM (+4%), 30% 1-RM (+20%) and 40% 1 RM (+15%). No differences were found between conditions at 50% 1-RM. Area under the force-power curve with HIP was greater (p < 0.05) than with CC and LIP. In conclusion, results of this study indicate that the use of a HIP (100% 1-RM) in trained participants results in significantly greater power output during the concentric phase of a multi-joint exercise when compared to standard concentric movement. PMID- 27557280 TI - Postextraction Separation, On-Board Storage, and Catalytic Conversion of Methane in Natural Gas: A Review. AB - In today's perspective, natural gas has gained considerable attention, due to its low emission, indigenous availability, and improvement in the extraction technology. Upon extraction, it undergoes several purification protocols including dehydration, sweetening, and inert rejection. Although purification is a commercially established technology, several drawbacks of the current process provide an essential impetus for developing newer separation protocols, most importantly, adsorption and membrane separation. This Review summarizes the needs of natural gas separation, gives an overview of the current technology, and provides a detailed discussion of the progress in research on separation and purification of natural gas including the benefits and drawbacks of each of the processes. The transportation sector is another growing sector of natural gas utilization, and it requires an efficient and safe on-board storage system. Compressed natural gas (CNG) and liquefied natural gas (LNG) are the most common forms in which natural gas can be stored. Adsorbed natural gas (ANG) is an alternate storage system of natural gas, which is advantageous as compared to CNG and LNG in terms of safety and also in terms of temperature and pressure requirements. This Review provides a detailed discussion on ANG along with computation predictions. The catalytic conversion of methane to different useful chemicals including syngas, methanol, formaldehyde, dimethyl ether, heavier hydrocarbons, aromatics, and hydrogen is also reviewed. Finally, direct utilization of methane onto fuel cells is also discussed. PMID- 27557282 TI - Frederico Simoes Barbosa, one hundred years: a kaleidoscope of memories. PMID- 27557281 TI - A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release. AB - Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb(3+)/Er(3+) codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy. PMID- 27557283 TI - [The Aggeu Magalhaes Institute and its symbolic figure: Frederico Simoes Barbosa]. PMID- 27557284 TI - [Interdisciplinarity in epidemiological research: some lessons from the pioneering work of Frederico Simoes Barbosa]. PMID- 27557285 TI - [Professor Frederico Simoes Barbosa and the University of Brasilia]. PMID- 27557286 TI - [Professor Frederico Simoes Barbosa and his contribution to Brazilian epidemiology]. PMID- 27557287 TI - [Crossed paths: the role of Frederico Simoes Barbosa in the constitution of Public Health]. PMID- 27557288 TI - [Frederico Simoes Barbosa and the plague]. PMID- 27557289 TI - [Frederico, my father]. PMID- 27557291 TI - [Frederico Simoes Barbosa: a researcher ahead of his time]. PMID- 27557290 TI - [Frederico Simoes Barbosa: a life, a work, a school]. PMID- 27557292 TI - [Frederico Simoes Barbosa: a history of contributions to science and public health]. PMID- 27557293 TI - [Frederico Simoes Barbosa: a remarkable person of the Brazilian Public Health]. PMID- 27557294 TI - Consequences of Delayed, Unfinished, or Missed Nursing Care During Labor and Birth. AB - : : The purpose of this study was to examine the concept of delayed, unfinished, or missed nursing care when patient census and acuity exceed nurse staffing resources with nurses who care for women during labor and birth. Focus groups were held during which labor nurses were asked about aspects of nursing care that may be regularly delayed, unfinished, or completely missed during labor and birth, including possible reasons and potential consequences. Seventy-one labor nurses participated in 11 focus groups in 6 hospitals. Nurses focused on support and encouragement as aspects of care that they felt are essential but often not able to be performed when the unit is busy. Nurses seemed to assume technical features of care as a "given" in the background and not always noticed unless missed. They voiced concerns about risks to maternal and fetal well-being when they were short-staffed. Potential outcomes were discussed including cesarean birth, depressed infants at birth, hemorrhage, and negative effects on patient satisfaction, successful breast-feeding, and the overall patient experience. CONCLUSION: When essential aspects of nursing care are delayed, unfinished, or completely missed, there are potentially negative implications for numerous patient outcomes and patient safety is at risk. PMID- 27557295 TI - Melanoma antigens are biomarkers for ipilimumab response. AB - BACKGROUND: Novel immunotherapy modalities significantly improve survival of patients with metastatic melanoma. However, CTLA-4-blocking monoclonal antibody ipilimumab is effective only in a small proportion of patients. Biomarkers for prediction of treatment response are indispensably needed. OBJECTIVE: To determine the utility of multimarker detection of circulating melanoma cells as prognostic and pharmacodynamic biomarker in patients with metastatic melanoma treated with ipilimumab. METHODS: Patients (n = 62) with metastatic melanoma in unresectable stage III or metastatic stage IV treated with ipilimumab were recruited prospectively. The values of four melanoma markers on circulating cells Melan-A, gp100, MAGE-3 and melanoma inhibitory antigen prior to the treatment and within the therapy were compared to the data collected at baseline - after the melanoma surgery. RESULTS: The immunotherapy pretreatment marker level was found to be prognostic of overall survival; lower levels were linked to longer survival time. Moreover, longitudinal follow-up of melanoma markers in patients treated with ipilimumab correlates with therapy response. A decline of marker levels by >30% at week 6 (in 83% of the responding subjects) to week 9 (in all responders) of ipilimumab administration was associated with response to therapy. Elevation of the tumour markers during the treatment precedes clinical progression and gives an early warning of treatment failure. CONCLUSION: Melanoma circulating cells hold potential as predictive and pharmacodynamic biomarker of immunotherapy. PMID- 27557296 TI - Development and validation of an LC-MS/MS quantitative method for endogenous deoxynucleoside triphosphates in cellular lysate. AB - The endogenous deoxynucleoside triphosphate (dNTP) pool includes deoxyadenosine triphosphate (dATP), deoxycytidine triphosphate (dCTP), deoxyguanosine triphosphate (dGTP) and thymidine triphosphate (TTP). The endogenous dNTP pool is regulated by complex enzymatic pathways that can be targeted by drugs, such as antimetabolites. In addition, these components compete with antiviral nucleos(t)ide analog triphosphates, contributing to the mechanism of pharmacologic action. This communication describes the development and validation of a sensitive method to quantify the intracellular dNTP pool in cellular lysates. The extraction process was optimized for dNTPs using an indirect strategy - the separation of mono-, di- and triphosphate moieties by strong anion exchange, dephosphorylation of target fractions to molar equivalent nucleosides - followed by sensitive quantitation using liquid chromatography-tandem mass spectrometry. The validated analytical range was 50-2500 fmol/sample for each dNTP. The assay was used to quantify dNTPs in peripheral blood mononuclear cells from 40 clinical research participants (n = 279 samples). Median (interquartile range) concentrations were 143 (116, 169) for dATP, 737 (605, 887) for dCTP, 237 (200, 290) for dGTP and 315 (220, 456) for TTP, in femtomoles per million cells. This method allows for future studies of endogenous dNTP disposition in subjects receiving antimetabolites or nucleos(t)ide analogs, or for other clinical scenarios. PMID- 27557297 TI - The Hard Work of Health Care Transformation. PMID- 27557298 TI - Uncertainty in the Era of Precision Medicine. PMID- 27557299 TI - The Abyss. PMID- 27557301 TI - A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. AB - BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.). PMID- 27557303 TI - Treatment of Patients with Cirrhosis. PMID- 27557300 TI - 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. AB - BACKGROUND: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70 gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. RESULTS: A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. CONCLUSIONS: Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5 year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.). PMID- 27557304 TI - IMAGES IN CLINICAL MEDICINE. Giant Thrombosed Intracranial Aneurysm. PMID- 27557305 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 26-2016. A 28-Year-Old Woman with Back Pain and a Lesion in the Lumbar Spine. PMID- 27557306 TI - Increasing Precision in Adjuvant Therapy for Breast Cancer. PMID- 27557302 TI - Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. AB - BACKGROUND: Daratumumab, a human IgGkappa monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P=0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3% and 32.9%, respectively), anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, respectively). Infusion related reactions that were associated with daratumumab treatment were reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 98.2% of these patients, they occurred during the first infusion. CONCLUSIONS: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone. (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT02136134.). PMID- 27557307 TI - Treatment of Medically Refractory Essential Tremor. PMID- 27557308 TI - Body Fatness and Cancer--Viewpoint of the IARC Working Group. PMID- 27557309 TI - Rate Control or Rhythm Control for Atrial Fibrillation after Heart Surgery. PMID- 27557310 TI - Rate Control or Rhythm Control for Atrial Fibrillation after Heart Surgery. PMID- 27557311 TI - Rate Control or Rhythm Control for Atrial Fibrillation after Heart Surgery. PMID- 27557312 TI - Rate Control or Rhythm Control for Atrial Fibrillation after Heart Surgery. PMID- 27557313 TI - Rate Control or Rhythm Control for Atrial Fibrillation after Heart Surgery. PMID- 27557314 TI - Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. PMID- 27557315 TI - Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. PMID- 27557316 TI - Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. PMID- 27557317 TI - Colorectal Cancer on the Decline. PMID- 27557318 TI - Colorectal Cancer on the Decline. PMID- 27557319 TI - Colorectal Cancer on the Decline. PMID- 27557320 TI - Bariatric Surgery and Preterm Birth. PMID- 27557321 TI - IMAGES IN CLINICAL MEDICINE. A Sneeze. PMID- 27557322 TI - Introducing Allergenic Foods in Infants. PMID- 27557323 TI - Introducing Allergenic Foods in Infants. PMID- 27557324 TI - Introducing Allergenic Foods in Infants. PMID- 27557325 TI - Introducing Allergenic Foods in Infants. PMID- 27557326 TI - Ozanimod Treatment for Ulcerative Colitis. PMID- 27557327 TI - Ozanimod Treatment for Ulcerative Colitis. PMID- 27557328 TI - The Need for Postdischarge, Patient-Centered Data in Trauma. PMID- 27557329 TI - Change in Auxin and Cytokinin Levels Coincides with Altered Expression of Branching Genes during Axillary Bud Outgrowth in Chrysanthemum. AB - In the production and breeding of Chrysanthemum sp., shoot branching is an important quality aspect as the outgrowth of axillary buds determines the final plant shape. Bud outgrowth is mainly controlled by apical dominance and the crosstalk between the plant hormones auxin, cytokinin and strigolactone. In this work the hormonal and genetic regulation of axillary bud outgrowth was studied in two differently branching cut flower Chrysanthemum morifolium (Ramat) genotypes. C17 is a split-type which forms an inflorescence meristem after a certain vegetative period, while C18 remains vegetative under long day conditions. Plant growth of both genotypes was monitored during 5 subsequent weeks starting one week before flower initiation occurred in C17. Axillary bud outgrowth was measured weekly and samples of shoot apex, stem and axillary buds were taken during the first two weeks. We combined auxin and cytokinin measurements by UPLC MS/MS with RT-qPCR expression analysis of genes involved in shoot branching regulation pathways in chrysanthemum. These included bud development genes (CmBRC1, CmDRM1, CmSTM, CmLsL), auxin pathway genes (CmPIN1, CmTIR3, CmTIR1, CmAXR1, CmAXR6, CmAXR2, CmIAA16, CmIAA12), cytokinin pathway genes (CmIPT3, CmHK3, CmRR1) and strigolactone genes (CmMAX1 and CmMAX2). Genotype C17 showed a release from apical dominance after floral transition coinciding with decreased auxin and increased cytokinin levels in the subapical axillary buds. As opposed to C17, C18 maintained strong apical dominance with vegetative growth throughout the experiment. Here high auxin levels and decreasing cytokinin levels in axillary buds and stem were measured. A differential expression of several branching genes accompanied the different hormonal change and bud outgrowth in C17 and C18. This was clear for the strigolactone biosynthesis gene CmMAX1, the transcription factor CmBRC1 and the dormancy associated gene CmDRM1, that all showed a decreased expression in C17 at floral transition and an increased expression in C18 with continuous vegetative growth. These results offer a case study for Chrysanthemum, showing an altered cytokinin to auxin balance and differential gene expression between vegetative growth with apical dominance and transition to generative growth with loss of apical dominance and axillary bud outgrowth. This suggests a conservation of several aspects of the hormonal and genetical regulation of bud outgrowth in Chrysanthemum. Furthermore, 15 previously uncharacterised genes in chrysanthemum, were described in this study. Of those genes involved in axillary bud outgrowth we identified CmDRM1, CmBRC1 and CmMAX1 as having an altered expression preceding axillary bud outgrowth, which could be useful as markers for bud activity. PMID- 27557330 TI - A genomics-based systems approach towards drug repositioning for rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of synovial joints. RA affects up to 1 % of the population worldwide. Currently, there are no drugs that can cure RA or achieve sustained remission. The unknown cause of the disease represents a significant challenge in the drug development. In this study, we address this challenge by proposing an alternative drug discovery approach that integrates and reasons over genetic interrelationships between RA and other genetic diseases as well as a large amount of higher-level drug treatment data. We first constructed a genetic disease network using disease genetics data from Genome-Wide Association Studies (GWAS). We developed a network-based ranking algorithm to prioritize diseases genetically-related to RA (RA-related diseases). We then developed a drug prioritization algorithm to reposition drugs from RA-related diseases to treat RA. RESULTS: Our algorithm found 74 of the 80 FDA-approved RA drugs and ranked them highly (recall: 0.925, median ranking: 8.93 %), demonstrating the validity of our strategy. When compared to a study that used GWAS data to directly connect RA-associated genes to drug targets ("direct genetics-based" approach), our algorithm ("indirect genetics-based") achieved a comparable overall performance, but complementary precision and recall in retrospective validation (precision: 0.22, recall: 0.36; F1: 0.27 vs. precision: 0.74, recall: 0.16; F1: 0.28). Our approach performed significantly better in novel predictions when evaluated using 165 not-yet-FDA-approved RA drugs (precision: 0.46, recall: 0.50; F1: 0.47 vs. precision: 0.40, recall: 0.006; F1: 0.01). CONCLUSIONS: In summary, although the fundamental pathophysiological mechanisms remain uncharacterized, our proposed computation-based drug discovery approach to analyzing genetic and treatment interrelationships among thousands of diseases and drugs can facilitate the discovery of innovative drugs for treating RA. PMID- 27557331 TI - Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation. AB - BACKGROUND: End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES: To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,((r)) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,((r)) Sanofi) as induction therapy and immediate release tacrolimus [Adoport((r)) (Sandoz); Capexion((r)) (Mylan); Modigraf((r)) (Astellas Pharma); Perixis((r)) (Accord Healthcare); Prograf((r)) (Astellas Pharma); Tacni((r)) (Teva); Vivadex((r)) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,((r)) Astellas Pharma); belatacept (BEL) (Nulojix,((r)) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip((r)) (Zentiva), CellCept((r)) (Roche Products), Myfenax((r)) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,((r)) Pfizer) and everolimus (Certican,((r)) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. DATA SOURCES: Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost). REVIEW METHODS: Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS: Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost effective at L20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost effective at L20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at L20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost effectiveness threshold of L20,000-30,000 per QALY, BAS and TAC are cost effective in all considered combinations; MMF was also cost-effective with CSA but not TAC. LIMITATIONS: The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence. CONCLUSIONS: TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at L20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost effective at L20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013544. FUNDING: The National Institute for Health Research HTA programme. PMID- 27557333 TI - Evaluation of Wet Cupping Therapy: Systematic Review of Randomized Clinical Trials. AB - BACKGROUND: Wet cupping is a widely used traditional therapy in many countries, which justifies a continuous scientific evaluation of its efficacy and safety. OBJECTIVES: To perform a systematic review to critically evaluate and update the available evidence of wet cupping in traditional and complementary medicine. METHODS: Ten electronic databases were searched from their inceptions to February 2016. Included studies were randomized clinical trials (RCTs) that evaluated wet cupping against any type of control interventions in patients with any clinical condition, as well as healthy individuals. Cochrane risk of bias tool was used to appraise the included RCTs. RESULTS: Fourteen RCTs met the eligibility criteria. The included studies evaluated the following clinical conditions: nonspecific low back pain (NSLBP), hypertension, brachialgia, carpal tunnel syndrome (CTS), chronic neck pain, metabolic syndrome, migraine headaches, oxygen saturation in smokers with chronic obstructive pulmonary disease (COPD), and oral and genital ulcers due to Behcet disease. Two RCTs evaluated physiologic and biochemical parameters of healthy individuals. Overall, 9 RCTs favored wet cupping over various control interventions in NSLBP (n = 2), hypertension (n = 1), brachialgia (n = 1), CTS (n = 1), chronic neck pain (n = 2), oxygen saturation in smokers with COPD (n = 1), and oral and genital ulcers due to Behcet disease (n = 1). Five RCTs showed no statistically significant between-group differences: NSLBP (n = 1), metabolic syndrome (n = 1), migraine headaches (n = 1), and physiologic and biochemical parameters of healthy individuals (n = 2). Included RCTs had a variable risk of bias across all domains and suffered methodologic limitations. CONCLUSIONS: There is a promising evidence in favor of the use of wet cupping for musculoskeletal pain, specifically NSLBP, neck pain, CTS, and brachialgia. Better quality trials are needed to generate solid evidence and firmly inform policy makers. PMID- 27557332 TI - Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus-Infected Adults: Veterans Aging Cohort Study. AB - Importance: With the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)-infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population. Objective: To examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV. Design, Setting, and Participants: Included in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998-2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015. Main Outcomes and Measures: Incident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009. Results: The mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05-1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04 1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05-1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00-1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87-1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI. Conclusions and Relevance: We report novel evidence that HIV infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population. PMID- 27557334 TI - Overcoming Barriers to Sustained Engagement in Mental Health Care: Perspectives of Rural Veterans and Providers. AB - PURPOSE: To better understand the attitudes, beliefs, and values that influence use of mental health care among rural veterans. METHODS: In-depth, semistructured interviews were conducted with 25 rural veterans and 11 rural mental health care providers in 4 states. Experienced qualitative interviewers asked participants about the attitudinal factors they thought most influenced rural veterans' decisions to seek and sustain mental health care. Verbatim transcriptions were analyzed using content analysis and constant comparison. FINDINGS: Rural veterans and their mental health care providers reported the same major attitudinal barriers to veterans' mental health treatment-seeking. Pre-eminent among those barriers was the importance rural veterans place on independence and self reliance. The centrality of self-reliance was attributed variously to rural, military, religious, and/or gender-based belief systems. Stoicism, the stigma associated with mental illness and health care, and a lack of trust in the VA as a caring organization were also frequently mentioned. Perceived need for care and the support of other veterans were critical to overcoming attitudinal barriers to initial treatment-seeking, whereas critical facilitators of ongoing service use included "warm handoffs" from medical to mental health care providers, perceived respect and caring from providers, as well as provider accessibility and continuity. CONCLUSIONS: Attitudes and values, like self-reliance, commonly associated with rural culture may play an important role in underutilization of needed mental health services. System support for peer and provider behaviors that generate trust and demonstrate caring may help overcome attitudinal barriers to treatment-seeking and sustained engagement in mental health care among rural veterans. PMID- 27557335 TI - Resource Availability Modulates the Cooperative and Competitive Nature of a Microbial Cross-Feeding Mutualism. AB - Mutualisms between species play an important role in ecosystem function and stability. However, in some environments, the competitive aspects of an interaction may dominate the mutualistic aspects. Although these transitions could have far-reaching implications, it has been difficult to study the causes and consequences of this mutualistic-competitive transition in experimentally tractable systems. Here, we study a microbial cross-feeding mutualism in which each yeast strain supplies an essential amino acid for its partner strain. We find that, depending upon the amount of freely available amino acid in the environment, this pair of strains can exhibit an obligatory mutualism, facultative mutualism, competition, parasitism, competitive exclusion, or failed mutualism leading to extinction of the population. A simple model capturing the essential features of this interaction explains how resource availability modulates the interaction and predicts that changes in the dynamics of the mutualism in deteriorating environments can provide advance warning that collapse of the mutualism is imminent. We confirm this prediction experimentally by showing that, in the high nutrient competitive regime, the strains rapidly reach a common carrying capacity before slowly reaching the equilibrium ratio between the strains. However, in the low nutrient regime, before collapse of the obligate mutualism, we find that the ratio rapidly reaches its equilibrium and it is the total abundance that is slow to reach equilibrium. Our results provide a general framework for how mutualisms may transition between qualitatively different regimes of interaction in response to changes in nutrient availability in the environment. PMID- 27557336 TI - Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus. AB - Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (beta = 0.11, P = 0.05) and TSH (beta = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis. PMID- 27557337 TI - Conceptual issues behind the Chinese translations of the term 'Bipolar Disorder'. AB - The paper examines the problems of the existing nomenclature in Chinese psychiatry with special reference to the Chinese translation of bipolar disorder in the context of stigma of mental illness in the Chinese culture. The development of the concept of bipolar disorder is reviewed, followed by a critical examination of the accuracy and validity of the current translation of bipolar disorder in the Chinese psychiatric literature. A new translation is suggested with consideration for literal accuracy and social acceptance. PMID- 27557338 TI - Relationship satisfaction in lesbian couples: Review, methodological critique, and research agenda. AB - There has been increased interest in and attention to understanding the characteristics associated with relationship satisfaction among same-sex couples. This review examines the individual, couple, and external factors associated with relationship satisfaction among contemporary lesbian couples, highlighting domains such as internalized homophobia, personality, communication, conflict, sex, stress, and social support. I discuss methodological concerns and future directions to advance research in this area. PMID- 27557339 TI - Safety Outcomes of NOTES Cholecystectomy Versus Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Natural orifice transluminal endoscopic surgery (NOTES) is an endoscopic technique whereby surgical interventions can be performed with a flexible endoscope passed through a natural orifice (mouth, vulva, urethra, anus) then through a transluminal opening of the stomach, vagina, bladder, or colon. Although in the early stage of research and development, NOTES has been clinically applied across the globe, above all the transvaginal cholecystectomy is among the most frequently performed procedures. In the existing 2 types of transvaginal routes, the hybrid NOTES cholecystectomy (NC) is more likely to be accepted. However, there has been controversy regarding the safety outcomes of hybrid NC in comparison with classical laparoscopic cholecystectomy (LC). The primary objective of this meta-analysis is to compare the characteristics between NC and classical LC. MATERIALS AND METHODS: A meta-analysis of eligible studies comparing NC with classical LC was performed to evaluate the safety outcomes including wound complications, other postoperative complications and intraoperative conversion between the 2 groups. RESULTS: Pooling 3 randomized controlled trials (n=157) and 7 nonrandomized trial (n=593) demonstrated that the rates of wound complications and other postoperative complications in NC group did not significantly differ from those of classical LC group [wound complications: ratio difference (RD)=-0.02, 95% confidence interval (CI) -0.04to 0.01, P=0.23; other postoperative complication: RD=-0.01; 95% CI, -0.03 to 0.02; P=0.6]. The intraoperative conversion rate in NC groups was higher than that of LC groups (RD=0.03; 95% CI, 0.01-0.06; P=0.02). CONCLUSIONS: There is no significate difference between the safety of NC and laparoscope cholecystectomy. NC is associated with a higher rate of intraoperative conversion when compared with LC. It is worthy of further promotion and validation in clinical settings. PMID- 27557340 TI - The Prevalence, Clinical, and Molecular Characteristics of Congenital Hypothyroidism Caused by DUOX2 Mutations: A Population-Based Cohort Study in Guangzhou. AB - Thyroid dyshormonogenesis (DH) has recently been reported to be more frequently associated with mutations in the dual oxidase 2 (DUOX2) gene. The present study was aimed to investigate the prevalence, clinical, and molecular characteristics of congenital hypothyroidism (CH) caused by DUOX2 mutations in Guangzhou. A population-based cohort of 156 patients with CH was recruited based on neonatal screening among 433 578 newborns born in Guangzhou from 2011 to 2012. Genetic analysis of DUOX2 was performed in 96 patients with suspected thyroid dyshormonogenesis (SDH) by PCR-amplified direct sequencing. Apart from 2 cases without ultrasonographic data, 118 (76.6%) of the 156 patients were classified as SDH and 36 (23.4%) as thyroid dysgenesis (TD) according to thyroid ultrasound at diagnosis. Genetic analysis revealed 23 different variants in 60 unrelated individuals (60/96, 62.5%), including 13 novel variants that were absent from HGMD, dbSNP databases, and the 50 normal controls. The novel missense variants were predicted to be pathogenic by SIFT and PolyPhen-2. The p.K530X was the most common mutation. Ninety-three percent of mutant alleles occurred in exons 5, 6, 9, 14, 17, 20, 25, 27, and 28. There were no significant differences in phenotypes between biallelic and monoallelic variants cases or between with-DUOX2 and non-DUOX2 variants cases. Most patients with DUOX2 defects (78.2%) were transient CH. In conclusion, the prevalence of DUOX2 pathogenic variants was high (62.5%) in this cohort. Thirteen novel probably pathologic variants were reported. The p.K530X was the most common mutation in the Chinese population. There was no correlation between DUOX2 genotypes and clinical phenotypes. PMID- 27557341 TI - Thyroid Function and its Implications in Oxidative Stress Influencing the Pathogenesis of Osteoporosis in Adults with Down Syndrome: A Cohort Study. AB - People with Down syndrome (DS) show lower bone mass density (BMD) and a higher prevalence of hypothyroidism compared to general population. Furthermore, DS is a well-known high oxidative stress (OS) condition because genes involved in OS map on chromosome 21. Thyroid function too is involved in OS. Since both thyroid function and OS lead to lower BMD and osteoporotic fractures, we have explored correlations among BMD, thyroid hormones, and parameters of OS in DS adults. A total of 105 DS patients (48 males; 21-71 years; mean BMI 28.88+/-7.12 kg/m(2)) were enrolled in a cohort study, 48 of them undergoing thyroid replacement therapy. We evaluated thyroid function, BMD, and total antioxidant capacity (TAC) in blood plasma. TAC was assayed by H2O2-metmyoglobin system, as source of radicals, and by the chromogenous ABTS, with a latency time (LAG) in the appearance of its cation ABTS+proportional to antioxidant concentration. BMD was evaluated with DEXA, using WHO criteria to classify osteoporosis. Low BMD was found in 83.78% of patients. TSH and LAG did not correlate with BMD. Nevertheless, LAG significantly correlates to Z-scores estimated at the lumbar spine (r(2)=0.558; p=0.03) in hypothyroid patients. Our data show that low TAC could be more associated with reduced BMD rather than TSH itself in DS patients and that the OS could have a role in the pathogenesis of osteoporosis regarding the hypothyroid subgroup. PMID- 27557342 TI - Effects of Polymorphisms in NR1H4, NR1I2, SLCO1B1, and ABCG2 on the Pharmacokinetics of Rosuvastatin in Healthy Chinese Volunteers. AB - The nuclear receptors (NR)-farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2)-have important effects on the expression of genes related to the pharmacokinetics (PKs) of rosuvastatin. This study was designed to investigate whether the genetic variants in drug disposition genes (SLCO1B1 and ABCG2) combined with their upstream regulators (NR1H4 and NR1I2) would affect the PKs of rosuvastatin in a Chinese population. Sixty-one healthy male volunteers were enrolled and the plasma concentrations of rosuvastatin were measured using the liquid chromatographic-tandem mass spectrometry/MS method. All subjects were analyzed and grouped according to the genotypes of NR1H4, NR1I2, SLCO1B1, and ABCG2. The exposure of rosuvastatin was higher in subjects carrying the SLCO1B1 521C or ABCG2 421A allele compared with noncarriers. No association was observed of single-nucleotide polymorphisms in NR1H4 or NR1I2 genes with the PKs of rosuvastatin. After adjusting for the 421C>A and 521T>C variants, the Cmax in subjects with NR1I2 63396TT wild type were about 2-fold of those of NR1I2 mutant type (63396CC and CT) (10.7 vs. 20.4 ng/mL, P = 0.023), whereas no significant differences were observed for other parameters. Polymorphisms investigated in the genes of NR1H4 and NR1I2 seemed to play no significant role in the disposition of rosuvastatin. PMID- 27557343 TI - Angular compounding by full-channel B-scan modulation encoding for optical coherence tomography speckle reduction. AB - We describe an angular compounding method by full-channel B-scan modulation encoding for speckle reduction in optical coherence tomography. The complex valued spectral interferogram (SI) is reconstructed by removing one of the conjugate terms in the depth space. Fourier transform of the complex SI along the lateral direction enables a full-channel (with both negative and positive Fourier space) for B-scan modulation in the spatial frequency (nu) domain. A full-size probe beam, determined by the scanning mirror size, is centered on the mirror pivot, which allows the negative and positive half-channels working in parallel. Compared with the existing method, where only a half-channel (negative or positive) works alone, the proposed full-channel method offers more than twice the performance in speckle reduction. The feasibility of the proposed full-space approach is validated through both the phantom and in vivo human thumbnail experiments. PMID- 27557344 TI - Calibration of optical coherence tomography angiography with a microfluidic chip. AB - A microfluidic chip with microchannels ranging from 8 to 96 MUm was used to mimic blood vessels down to the capillary level. Blood flow within the microfluidic channels was analyzed with split-spectrum amplitude-decorrelation angiography (SSADA)-based optical coherence tomography (OCT) angiography. It was found that the SSADA decorrelation value was related to both blood flow speed and channel width. SSADA could differentiate nonflowing blood inside the microfluidic channels from static paper. The SSADA decorrelation value was approximately linear with blood flow velocity up to a threshold Vsat of 5.83+/-1.33 mm/s (mean+/-standard deviation over the range of channel widths). Beyond this threshold, it approached a saturation value Dsat. Dsat was higher for wider channels, and approached a maximum value Dsm as the channel width became much larger than the beam focal spot diameter. These results indicate that decorrelation values (flow signal) in capillary networks would be proportional to both flow velocity and vessel caliber but would be capped at a saturation value in larger blood vessels. These findings are useful for interpretation and quantification of clinical OCT angiography results. PMID- 27557346 TI - Consecutive Outbreaks of Enterotoxigenic Escherichia coli O6 in Schools in South Korea Caused by Contamination of Fermented Vegetable Kimchi. AB - BACKGROUND: Two outbreaks of gastroenteritis occurred in South Korea, affecting a middle school in the Jeollanam-do province in 2013 (Outbreak 1) and 10 schools in the Incheon province in 2014 (Outbreak 2). We investigated the outbreaks to identify the pathogen and mode of transmission. METHODS: A retrospective cohort study was conducted in the Outbreak 1; and case-control studies were performed for the Outbreak 2. Samples from students, environments, and preserved food items were collected and pulsed-field gel electrophoresis (PFGE) was conducted to identify strains of pathogen. RESULTS: We identified 167 and 1022 students who met the case definition (>=3 loose stools in any 24-h period) in the Outbreaks 1 and 2, respectively. The consumption of cabbage kimchi and young radish kimchi were significantly associated with the illness. Adjusted odds ratios of kimchi were 2.62-11.74. In the Outbreak 1, cabbage kimchi was made and consumed in the school restaurant and in the Outbreak 2, young radish kimchi was supplied by food company X and distributed to all the 10 schools in the Incheon province. Enterotoxigenic Escherichia coli (ETEC) O6 was isolated from fecal samples in 375 cases (33.9%) and from kimchi samples. PFGE patterns of the outbreak strains isolated from cases and food were indistinguishable in each outbreak. CONCLUSION: The suspected food vehicle in these two consecutive outbreaks was kimchi contaminated with ETEC O6. We recommend continued monitoring and stricter sanitation requirements for the food supply process in Korea, especially in relation to kimchi. PMID- 27557345 TI - Changes in cytokinins are sufficient to alter developmental patterns of defense metabolites in Nicotiana attenuata. AB - Plant defense metabolites are well known to be regulated developmentally. The optimal defense (OD) theory posits that a tssue's fitness values and probability of attack should determine defense metabolite allocations. Young leaves are expected to provide a larger fitness value to the plant, and therefore their defense allocations should be higher when compared with older leaves. The mechanisms that coordinate development with defense remain unknown and frequently confound tests of the OD theory predictions. Here we demonstrate that cytokinins (CKs) modulate ontogeny-dependent defenses in Nicotiana attenuata. We found that leaf CK levels highly correlate with inducible defense expressions with high levels in young and low levels in older leaves. We genetically manipulated the developmental patterns of two different CK classes by using senescence- and chemically inducible expression of CK biosynthesis genes. Genetically modifying the levels of different CKs in leaves was sufficient to alter ontogenic patterns of defense metabolites. We conclude that the developmental regulation of growth hormones that include CKs plays central roles in connecting development with defense and therefore in establishing optimal patterns of defense allocation in plants. PMID- 27557348 TI - Life Stress, Race, and Abnormal Glucose Metabolism in Postmenopausal Women. PMID- 27557347 TI - Targeted Isolation of Indolopyridoquinazoline Alkaloids from Conchocarpus fontanesianus Based on Molecular Networks. AB - A dichloromethane-soluble fraction of the stem bark of Conchocarpus fontanesianus showed antifungal activity against Candida albicans in a bioautography assay. Off line high-pressure liquid chromatography activity-based profiling of this extract enabled a precise localization of the compounds responsible for the antifungal activity that were isolated and identified as the known compounds flindersine (17) and 8-methoxyflindersine (18). As well as the identification of the bioactive principles, the ultra-high-pressure liquid chromatography-high resolution mass spectrometry metabolite profiling of the dichloromethane stem bark fraction allowed the detection of more than 1000 components. Some of these could be assigned putatively to secondary metabolites previously isolated from the family Rutaceae. Generation of a molecular network based on MS(2) spectra indicated the presence of indolopyridoquinazoline alkaloids and related scaffolds. Efficient targeted isolation of these compounds was performed by geometric transfer of the analytical high-pressure liquid chromatography profiling conditions to preparative medium-pressure liquid chromatography. This yielded six new indolopyridoquinazoline alkaloids (5, 16, 19-22) that were assigned structurally. The medium-pressure liquid chromatography separations afforded additionally 16 other compounds. This work has demonstrated the usefulness of molecular networks to target the isolation of new natural products and the value of this approach for dereplication. A detailed analysis of the constituents of the stem bark of C. fontanesianus was conducted. PMID- 27557349 TI - Focusing the Neuroscience and Societal Implications of Cognitive Enhancers. AB - Cognitive enhancement can benefit the individual and society, but also has associated risks and ethical concerns. Cognitive-enhancing drugs are used in the treatment of neuropsychiatric disorders. Nonpharmacological strategies are also emerging, which have the potential to improve motivational deficits associated with neuropsychiatric symptoms and should be prioritized for development. The increasing lifestyle use of "smart" and other drugs indicates the desire for healthy people to improve themselves. Safety and ethical implications are discussed. PMID- 27557351 TI - MOF-Derived Tungstated Zirconia as Strong Solid Acids toward High Catalytic Performance for Acetalization. AB - A strong solid acid, tungstated zirconia (WZ), has been prepared first using tungstate immobilized UiO-66 as precursors through a "double-solvent" impregnation method under mild calcination temperature. With moderate W contents, the as-synthesized WZ catalysts possess a high density of acid sites, and the proper heat treatment also has facilely led to a bunch of oligomeric tungsten clusters on stabilized tetragonal ZrO2. The resultant solid acids show an improved catalytic performance toward the benzaldehyde's acetalization in comparison with traditional zirconium hydroxide-prepared WZ. Notably, due to large surface area and additionally introduced strong acid sites, the MOF-derived WZ catalysts afforded conversion up to 86.0%. The facile method endows the WZ catalysts with superior catalytic activities and excellent recyclability, thus opening a new avenue for preparation of metal oxide-based solid superacids and superbases. PMID- 27557350 TI - Safety of intravenous iron use in chronic kidney disease. AB - PURPOSE OF REVIEW: Iron deficiency anaemia (IDA) is common and associated with fatigue, reduced quality of life and poorer clinical outcomes. Treatment with oral iron is often inadequate and international guidelines recommend intravenous (i.v.) iron as the preferred option for the treatment of IDA in certain clinical situations. In this review, we assess the safety of using i.v. iron with a particular focus on patients with chronic kidney disease. RECENT FINDINGS: Recent publications have raised safety concerns regarding the incidence of serious reactions accompanying i.v. infusion, as well as the subsequent risk of infections and cardiovascular events. Methodological flaws influence the interpretation of these data that lack evidence from the use of modern irons. The latter have been investigated in several randomized control trials. SUMMARY: There is a need for better understanding and definition of the nature of i.v. iron reactions, as many are nonserious infusion reactions rather than true anaphylaxis. Retrospective identification of anaphylaxis is difficult and we suggest the importance of reanalysing data using fatalities or standardized terms as outcome measures. With the exception of high molecular weight iron dextran, serious or life-threatening reactions are rare with the use of i.v. irons, and they can be used safely for the treatment of IDA. PMID- 27557352 TI - Editors' Note. PMID- 27557353 TI - Basic sanitation policy in Brazil: discussion of a path. AB - This article demonstrates that the position of dominance enjoyed by state sanitation companies dictates the public policy decision-making process for sanitation in Brazil. These companies' hegemony is explained here through the analysis of a path that generated political and economic incentives that have permitted its consolidation over time. Through the content analysis of the legislation proposed for the sector and the material produced by the stakeholders involved in the approval of new regulations for the sector in 2007, the study identifies the main sources of incentive introduced by the adoption of the National Sanitation Plan, which explain certain structural features of the current sanitation policy and its strong capacity to withstand the innovations proposed under democratic rule. PMID- 27557354 TI - Brazilian historiography and the environment: contributions by Sergio Buarque de Holanda and the contemporary environmental history debate. AB - Throughout the second half of the twentieth century, Brazilian historigraphical debate was profoundly marked by Sergio Buarque de Holanda. The problems of national identity, the occupation of the land, the social organization of Brazil and its civilizatory roots, the cultural exchanges and boundaries in inland parts, the perceptions and forms of appropriation of nature, and other topics covered by the author still echo in contemporary historical research. This article discusses how his main works contribute to environmental history, especially his interpretations of how human societies and the natural environment have affected one another. The role of nature, its metaphors, ideas, or images are the evidence of a history of Brazilian historiography. PMID- 27557355 TI - An eighteenth century travelling theodolite. AB - An old topographic compass displayed in a showroom of the Museu de Astronomia e Ciencias Afins (MAST), in Rio de Janeiro, Brazil, took our curiosity namely because of its resemblance to a theodolite, described by J.H. de Magellan. Not many things were known about its previous history. From the different documents studied, and the characteristics of this singular theodolite, it must have belonged to the collections of instruments acquired for the Brazilian border demarcations undertaken after the Santo Ildefonso Treaty, agreed to by the Portuguese and Spanish courts in 1777. Several instruments were bought in London, and supervised and chosen by Magellan, the Portuguese instruments expert. We present arguments in favour of this conclusion. PMID- 27557356 TI - [Humanitarianism, war and technological innovation: the case of the Spanish Red Cross]. PMID- 27557357 TI - [The Spanish Red Cross, the repatriation of soldiers during the colonial wars and the development of medical science in Spain, 1896-1950]. AB - This article examines the role played by the Spanish Red Cross (founded in 1864) in the introduction and spread of humanitarian technologies and the development of medical science in Spain, using the case study of medical care for sick and wounded soldiers repatriated during the wars in Cuba, the Philippines and Morocco, and analyzing the impact these measures had on health care and public health among the civilian population. The article shows how this organization set up health care for Spanish soldiers, establishing a network of specialized medical centers that were later also used to provide medical care for civilians and to address new public health problems. PMID- 27557358 TI - [Scientific communication and technological innovation in the first Red Cross, 1863-1876]. AB - The early years of the international Red Cross movement coincided with great technological changes in war medicine. The organizational peculiarities of the International Association for Relief of Wounded Soldiers in Campaign, set up by the Geneva Committee, and by the Red-Cross' national committees; the convergence in various professional conferences and publications of doctors from different national societies of this association; and the construction of a body of shared practical expertise tested during the Franco-Prussian War (1870-1871) provide keys for understanding the technological innovations introduced by the Spanish Red Cross during the third and last Carlist War (1872-1876). PMID- 27557359 TI - [A state of need: the Spanish Red Cross in Morocco, 1886-1927]. AB - This article studies the central role of nation-states in the Red Cross during the interwar period. In the late nineteenth century, Spain pioneered the creation of European-style humanitarian institutions in Morocco. However, its perennial instability as a state, aggravated by the colonial disaster of 1898, put an end to the regenerationist project of a Moroccan Red Cross. When the Spanish protectorate was established in 1912, the Spanish Red Cross was overshadowed by competition from its French counterpart, the internationalization of Tangiers and resistance from the local inhabitants. This culminated in the so-called Rif War of 1921-1927, a mixture of anticolonial revolt and international war that vividly exposed the ingrained deficiencies of the Spanish State and its Red Cross. PMID- 27557360 TI - [Technological innovation and humanitarianism in the transport of war wounded: Nicasio Landa's report on a new elastic suspension system for stretchers (Pamplona, May 29, 1875)]. AB - In May 1875, in the midst of a bloody civil conflict in Spain known as the Third Carlist War, Nicasio Landa, a medical officer with Military Health, wrote a report requesting authorization for the Spanish Red Cross, of which he was Inspector General, to adopt a new elastic suspension system for stretchers that he had designed, developed and tested. Intended above all for use in farm wagons still the most widely-used method of transporting the wounded at the time - it was an inexpensive, sturdy mechanism that improved patient comfort and could also be installed in ambulance carriages, railway carriages and hospital ships. An annotated version of the report is included, preceded by a presentation of its contents. PMID- 27557361 TI - [The new history of science: an interview with Dominique Pestre]. AB - Originally a physicist, Dominique Pestre is now a leading historian of science, particularly in the realm of the transformations that have marked the history of science and technology in recent decades. In this interview, he offers some of his thoughts on the role of science and knowledge in our contemporary world. He underscores the deep bonds between scientific knowledge and political and economic power and makes clear society's participation in this production. Critical of the notion of progress, Pestre invites us to also take the prejudicial effects of science into account. PMID- 27557362 TI - Prevalence of histopathological intestinal lesions and enteric pathogens in Dutch commercial broilers with time. AB - Intestinal disease has a major impact on the broiler industry due to economic and welfare reasons. Intestinal disease might occur due to a large number of reasons varying from well-defined pathogens to non-specific enteritis and complex syndromes. However, knowledge about the nature of intestinal disease and presence of enteric viruses in the Dutch broiler industry is largely absent. Therefore, a large-scale field study, in which 98 broiler flocks from 86 farms were sampled weekly, was started to assess the prevalence of histopathological lesions in the jejunum, a number of enterotropic viruses by real-time quantitative reverse transcriptase PCR (RT-qPCR) and coccidia by lesion scoring. Histopathological lesions indicative of intestinal disease were found in all flocks examined. The pathogens investigated were chicken astrovirus (99% of flocks positive), avian nephritis virus 3 (100%), rotavirus A (95%), rotavirus D (52%), reovirus (100%), Eimeria acervulina (94%), E. maxima (49%) and E. tenella (40%). The enteric viruses were more prevalent in the first weeks of the growing period, while coccidiosis was more frequently found at 4 and 5 weeks of age. The abundant presence of the enteric viruses and enteric disorders stresses the need to elucidate the role of these viruses in intestinal disease. Furthermore, the high prevalence of coccidiosis despite the use of anticoccidials shows that the current coccidial management programmes might be insufficient in controlling this disease. PMID- 27557363 TI - Early work on semiconductor quantum nanoelectronics in the Cavendish Laboratory. PMID- 27557364 TI - Fine motor skills enhance lexical processing of embodied vocabulary: A test of the nimble-hands, nimble-minds hypothesis. AB - Research suggests that fine motor skills (FMS) are linked to aspects of cognitive development in children. Additionally, lexical processing advantages exist for words implying a high body-object interaction (BOI), with initial findings indicating that such words in turn link to children's FMS-for which we propose and evaluate four competing hypotheses. First, a maturational account argues that any links between FMS and lexical processing should not exist once developmental variables are controlled for. Second, functionalism posits that any link between FMS and lexical processing arises due to environmental interactions. Third, the semantic richness hypothesis argues that sensorimotor input improves lexical processing, but predicts no links between FMS and lexical processing. A fourth account, the nimble-hands, nimble minds (NHNM) hypothesis, proposes that having greater FMS improves lexical processing for high-BOI words. In two experiments, the response latencies of preschool children (n = 90, n = 76, ages = 5;1) to 45 lexical items encompassing high-BOI, low-BOI, and less imageable words were measured, alongside measures of FMS, reasoning, and general receptive/expressive vocabulary. High-BOI words appeared to show unique links to FMS, which remained after accounting for low-BOI and less imageable words, general vocabulary, reasoning, and chronological age. Although further work is needed, the findings provide initial support for the NHNM hypothesis. PMID- 27557365 TI - Reptilian exposure to polycyclic aromatic hydrocarbons and associated effects. AB - Reptiles are an underrepresented taxon in ecotoxicological literature, and the means by which toxicants play a role in population declines are only partially understood. Among the contaminants of interest for reptiles are polycyclic aromatic hydrocarbons (PAHs), a class of organic compounds that is already a concern for numerous other taxa. The objectives of the present review are to summarize the existing literature on reptilian exposure to PAHs and synthesize general conclusions, to identify knowledge gaps within this niche of research, and to suggest future directions for research. Results confirm a relative scarcity of information on reptilian exposure to PAHs, although research continues to grow, particularly after significant contamination events. The orders Testudines and Squamata are better represented than the orders Crocodilia and Rhynchocephalia. For the taxonomic orders with relevant literature (all but Rhynchocephalia), some species are more frequently represented than others. Few studies establish solid cause-effect relationships after reptilian exposure to PAHs, and many more studies are suggestive of effect or increased risk of effect. Despite the scarcity of information in this area, researchers have already employed a wide variety of approaches to address PAH-related questions for reptiles, including molecular techniques, modeling, and field surveys. As more research is completed, a thoughtful interpretation of available and emerging data is necessary to make the most effective use of this information. Environ Toxicol Chem 2017;36:25-35. (c) 2016 SETAC. PMID- 27557366 TI - Cancer prevention in developing countries: a vision for preserving health in Mexico. PMID- 27557367 TI - Eradication of cervical cancer in Latin America. PMID- 27557368 TI - Cancer burden in Mexico: urgent challenges to be met. PMID- 27557369 TI - Cancer patterns, trends and projections in Latin America and the Caribbean: a global context. AB - OBJECTIVE: To develop a situation analysis encompassing the patterns and trends in cancer incidence and mortality in South and Central America and the Caribbean, with comparisons globally and with selected external countries. MATERIALS AND METHODS: Data on cancer incidence and mortality rates for 31 countries were obtained from the 2012 GLOBOCAN database. Incidence and mortality trends for selected countries were analysed with data from the Cancer Incidence in Five Continents (CI5) series and the WHO Mortality Database, respectively. RESULTS: In 2012, almost 1.1 million new cancer cases were estimated annually, with important variations in rates across countries. The most common cancer types were breast, prostate, colorectum and lung cancer; stomach and cervical cancer ranked high in less developed countries. Increasing trends were observed in prostate, breast and colorectal cancer; lung cancer mortality trends diverged among males and females, while cervix cancer incidence and stomach cancer mortality uniformly decreased. A 66% increase in cancer cases in the region by 2030 is projected based on population aging and growth. CONCLUSIONS: Cancer patterns and trends reflect the significant sociodemographic changes in the region: the growing burden imposes great challenges to national health care systems to implement cancer control actions, while improving cancer surveillance to effectively measure the response. PMID- 27557370 TI - The burden of cancer in Mexico, 1990-2013. AB - OBJECTIVE: To analyze mortality and incidence for 28 cancers by deprivation status, age and sex from 1990 to 2013. MATERIALS AND METHODS: The data and methodological approaches provided by the Global Burden of Disease (GBD 2013) were used. RESULTS: Trends from 1990 to 2013 show important changes in cancer epidemiology in Mexico. While some cancers show a decreasing trend in incidence and mortality (lung, cervical) others emerge as relevant health priorities (prostate, breast, stomach, colorectal and liver cancer). Age standardized incidence and mortality rates for all cancers are higher in the northern states while the central states show a decreasing trend in the mortality rate. The analysis show that infection related cancers like cervical or liver cancer play a bigger role in more deprived states and that cancers with risk factors related to lifestyle like colorectal cancer are more common in less marginalized states. CONCLUSIONS: The burden of cancer in Mexico shows complex regional patterns by age, sex, types of cancer and deprivation status. Creation of a national cancer registry is crucial. PMID- 27557371 TI - The burden of disease of cancer in the Mexican Social Security Institute. AB - OBJECTIVE: To estimate the disease burden of cancer in the affiliate population of the Mexican Social Security Institute (Instituto Mexicano del Seguro Social, IMSS) in 2010 by delegation. MATERIALS AND METHODS: The Disability-Adjusted Life Years (DALYs), Years of Life Lost (YLL) due to premature mortality and Years Lived with Disability/Disease (YLD) for 21 specific cancers and a subgroup of other malignant neoplasms were calculated based on the methodology of the Global Burden of Disease Study (GBD) for each of the 35 delegations of the IMSS. RESULTS: In 2010, cancer represented the fifth overall leading cause of disease burden in IMSS affiliates (16.72 DALYs/1000 affiliates). A total of 75% of the cancer disease burden in each delegation is due to ten specific cancers, particularly breast cancer, which ranks first in 82% of the delegations. Prostate cancer; tracheal, bronchial, and lung cancers; leukemia, and colorectal and stomach cancers occupy the second to fourth positions in each delegation. With the exception of breast and prostate cancer, for which the contribution of YLD to the DALYs was higher than 50%, the greatest contribution to the DALYs of the other cancers was premature mortality, which accounted for more than 90% of the DALYs in some cases. CONCLUSION: The results obtained in this study allow for the identification of intervention priorities with regard to cancer at the institutional level and also for the focus at the delegation level to be placed on cancers ranking in the top positions for disease burden. PMID- 27557373 TI - Cancer mortality in the Mexican Social Security Institute, 1989-2013. AB - Objetive: To analyze cancer mortality in affiliates of the Mexican Social Security Institute (Instituto Mexicano del Seguro Social - IMSS) and time trends in the risk of death due to cancer from 1989 to 2013. MATERIALS AND METHODS: A descriptive analysis of cancer mortality trends in beneficiaries of the IMSS was performed. Age- and sex-adjusted mortality rates were obtained using direct standardization with the WHO population. Changes in the risk of death due to cancer over time were evaluated using Poisson regression. RESULTS: The absolute number of deaths due to cancer doubled from 1989 to 2013 due to increasing age of the affiliate population. The risk of death among affiliates decreased for the majority of cancers except for colon and rectal cancer. CONCLUSION: The risk of dying from cancer among IMSS affiliates showed a marked decrease, which may be due to an increase in detection and opportune treatment. PMID- 27557372 TI - Utilization of hospital services for cancer care in Mexico. AB - OBJECTIVE: To analyze the utilization of hospital services for cancer care by location, sex, age group and care institution in Mexico from 2004-2013. MATERIALS AND METHODS: Time series study from 2004-2013, based on administrative records of hospital discharges for cancer in the health sector, including the private sector. RESULTS: The utilization rate increased significantly from 290 to 360 per 100 000 inhabitants. A total of 62% of hospital discharges related to malignant tumors were concentrated in eight types of cancer. Leukemia, breast and colorectal cancers almost doubled in the period. While lung cancer showed a decline among men, it increased among women. A total of 63.1% of cancer patients were women, and 81% of cases occurred in the public sector. From 2011, the Ministry of Health was the main provider of hospital services for cancer care. CONCLUSIONS: Increases in utilization were mainly found in the Ministry of Health, quite possibly as a result of the implementation of universal insurance. PMID- 27557374 TI - Cancer incidence and mortality in children in the Mexican Social Security Institute (1996-2013). AB - OBJECTIVE: To identify the cancer incidence and mortality in Mexican Social Security Institute beneficiary (MSSI-B) children during 1996-2013. MATERIALS AND METHODS: Both cancer cases (n=4 728) and deaths (n=2 378) were analyzed in MSSI-B children who were registered in five states of the Mexican Republic. The incidence and mortality trends and the incidences (rate x 1 000 000 children / year) of the type of cancer, age, sex, and place of residence were obtained. RESULTS: For both indicators (incidence and mortality), there was a downward trend for the period of 1996-2001 and a stable trend for 2002-2013. This occurred in the overall mortality and incidence trends of the Estado de Mexico and Chiapas and in the leukemia and the acute lymphoid subgroups. The annual overall incidence was 128 cases per 1 000 000 children. Leukemia, lymphomas, and central nervous system tumors were the principal cancer groups. CONCLUSIONS: Cancer mortality for the period of 2002-2013 did not diminish. Interinstitutional and/or international research should be designed to improve the care of these children. PMID- 27557375 TI - Historical distribution of central nervous system tumors in the Mexican National Institute of Neurology and Neurosurgery. AB - OBJECTIVE: To determine the frequency of central nervous system (CNS) tumors in the first fifty years of the National Institute of Neurology and Neurosurgery of Mexico Manuel Velasco Suarez (Instituto Nacional de Neurologia y Neurocirugia de Mexico, INNN) from 1965 to 2014. MATERIALS AND METHODS: A total of 16 116 institutional records of CNS tumors were analyzed. The frequency and distribution of CNS tumors were evaluated by tumor type, patient age and patient gender. The annual relationship between CNS tumors and surgical discharges (SD) over the last 20 years was estimated. RESULTS: The frequencies of most CNS tumors were consistent with those found worldwide, and the most common tumors were neuroepithelial tumors (33%), particularly astrocytic tumors (67%); meningeal tumors (26%); and pituitary tumors (20%). The incidence of pituitary tumors in these data was twice as high as that reported in other regions of the world, and the relationship between CNS tumors and SD was consistent over time (0.22-0.39). CONCLUSION: This study summarizes the largest sample of CNS tumor cases analyzed in Mexico and provides an important reference of the frequency of this tumor type in the country. This work will serve as a basis for conducting studies evaluating factors associated with the presence of CNS tumors and for identifying adequate public health interventions. PMID- 27557376 TI - Prostate cancer mortality according to marginalization status in Mexican states from 1980 to 2013. AB - OBJECTIVE: To assess prostate cancer (PC) mortality in Mexico from 1980 to 2013, according to the state marginalization level. MATERIALS AND METHODS: Using age adjusted rates in men >= 40 years old, we estimated trends and age-cohort-period effects of PC mortality from 1980-2013 according to state marginalization status by using a joinpoint regression model and a Poisson regression model proposed by Holford. RESULTS: The PC mortality risk has increased nationwide at a constant rate (2% annually) during the past 13 years. The highest annual increase was observed among states with very high (4.4%) and high (7.7%) marginalization rates. In contrast, states with very low levels of marginalization showed a significant reduction of 1.5% per year. The main changes were observed in the 1945-1950 birth year cohorts. CONCLUSIONS: Differences in PC mortality across regions of Mexico may reflect differences in the timing of the diagnosis and treatment of PC. PMID- 27557377 TI - Hospitalization and mortality in Mexico due to breast cancer since its inclusion in the catastrophic expenditures scheme. AB - OBJECTIVE: To compare trends in hospital discharges and mortality due to breast cancer (BC) in Mexico from 2004 to 2012 by insurance condition before and after incorporating BC comprehensive treatment into the System of Social Protection in Health (Sistema de Protreccion Social en Salud, SPSS) in 2007. MATERIALS AND METHODS: Data on BC hospital discharges and mortality reported in women aged 25 years and over were obtained from the National Health Information System. Mortality rates were adjusted by age and state. RESULTS: At the national level, a growing tendency in hospital discharges was observed, mainly for women without social security, while mortality rate remained constant. Mortality rates by state show that lower marginalization index corresponded to higher mortality. CONCLUSIONS: A differential behavior was observed among women according to insurance condition, partly due to the inclusion of BC treatment in the SPSS. PMID- 27557378 TI - Triage strategies in cervical cancer detection in Mexico: methods of the FRIDA Study. AB - OBJECTIVE: This paper describes the study design and baseline characteristics of the study population, including the first 30 829 women who enrolled in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA Study). This is a large population based study that is evaluating the performance and cost-effectiveness of different triage strategies for high-risk HPV (hrHPV) positive women in Mexico. MATERIALS AND METHODS: The target population is more than 100 000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. Since August 2013, all women in the region have been invited to enroll in the study. The study participants are evaluated to determine hrHPV infection using the Cobas 4800 HPV test. The HPV-16/18 genotyping and cytology triage strategies are performed as reflex tests in all hrHPV-positive participants. Women with a positive HPV-16/18 test and/or abnormal cytology (atypical squamous cells of undetermined significance or worse, ASCUS+) are referred for colposcopy evaluation, where a minimum of four biopsies and an endocervical sample are systematically collected. Histologic confirmation is performed by a standardized panel of pathologists. RESULTS: Among the 30 829 women who have been screened, the overall prevalence of hrHPV is 11.0%. The overall prevalence of HPV16 and HPV18 are 1.5% and 0.7%, respectively. Cytological abnormalities (ASCUS+) were detected in 11.8% of the hrHPV-positive women. A total of 27.0% (920/3,401) of the hrHPV-positive women were referred to colposcopy because of a positive HPV16/18 test and/or abnormal reflex cytology, (31.6% had only ASCUS+, 53.6% were HPV16/18 positive with a normal cytology result, and 9.5% were positive to both triage tests). CONCLUSION: The results of this study will help policy makers and health service providers establish the best practices for triage in cervical cancer screening in Mexico and other countries. PMID- 27557379 TI - HPV vaccination impact on a cervical cancer screening program: methods of the FASTER-Tlalpan Study in Mexico. AB - OBJECTIVE: To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. MATERIALS AND METHODS: A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. CONCLUSION: The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals. PMID- 27557380 TI - Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women. AB - OBJECTIVE: To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARgamma (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). MATERIALS AND METHODS: Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. RESULTS: In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. CONCLUSION: Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC. PMID- 27557381 TI - Estimating the indirect costs associated with the expected number of cancer cases in Mexico by 2020. AB - OBJECTIVE: To estimate the indirect costs generated by adults with cancer in Mexico from 2002-2020. MATERIALS AND METHODS: Using information from national sources and the national cancer incidence from GLOBOCAN, we estimated income lost due to premature death (ILPD), short-term benefits (STBs), disability pensions (DPs), and opportunity costs for the carer (OCCs) generated by patients with cancer. Amounts were reported in Mexican pesos. RESULTS: We estimated 23 359 deaths and 216 679 new cases of cancer by 2020, which would be associated with a total indirect cost of 20.15 billion Mexican pesos. Men are expected to generate 54.9% of these costs. ILPD is expected to comprise the highest percentage of the cost (60%), followed by OCCs (22%), STBs (17%) and DPs (1%). CONCLUSIONS: From an economic perspective, the results emphasize the need to strengthen preventive interventions and early detection of cancer among adults to reduce its effect on the productivity of Mexico. PMID- 27557382 TI - Effect of care-delivery delay on the survival of Mexican women with breast cancer. AB - OBJECTIVE: To estimate the effect of care-delivery delays on survival among women with breast cancer. MATERIALS AND METHODS: A retrospective analysis of 854 women attending 11 hospitals from 2007-2009 was carried out. Kaplan-Meier estimators and a Cox proportional-risk model were employed. RESULTS: A total of 10.5% of cases were diagnosed in stage I. 82% of sampled women delayed care for more than 67 days between noticing a symptom and initiating treatment. The median time from receipt of results of the mammography to biopsy was 31 days (IQR 14-56). Compared with those who were in quartile I (Q1), survival was lower among those in Q3 and Q4 (HR=1.68, 95%CI 0.94-3.00; HR=1.76, 95% CI 1.04-2.98, respectively). CONCLUSIONS: To increase survival, it is suggested that the time between receipt of the mammography results and diagnostic biopsy be reduced. PMID- 27557383 TI - Tobacco and cancer: epidemiology and new perspectives of prevention and monitoring in Mexico. AB - Tobacco smoking is causal risk factor of at least 16 different types of cancer. In Mexico, smoking causes 6 035 premature deaths annually of lung cancer and 5 154 from other types. Additionally, 16 408 new smoking- attributable cases are diagnosed, causing high costs in the Mexican health sector. The WHO Framework Convention on Tobacco Control is the global strategy to reduce morbidity and mortality caused by this risk factor. Four more cost-effective strategies to ensure the population benefit are: i) increase tobacco taxes, ii) create 100% smoke-free environments, iii) warn damage through health warnings with pictograms and iv) total ban of advertising and promotion. Mexico is call upon to implement with determination this comprehensive strategy to reduce cancer mortality and assuring the health population. PMID- 27557384 TI - The role of diet in cancer: the epidemiologic link. AB - Diet is an important modifiable risk factor for cancer. Adequate diet modification may play a key role in reducing the incidence of some cancers. A growing body of epidemiological evidence suggested links of some nutritional exposures with individual cancers. This review updates and summarises the existing data on diet related factors for cancer prevention, evaluated in 2007 by World Cancer Research Fund/American Institute for Cancer Research and identifies the areas where more research is needed. Mechanisms of action of nutrients are discussed. For cancer prevention, more apparent association pertains to the role of foods from plant origin, processed meat products and alcohol. There is a lack of evidence to clarify the relationship of dairy and cereal products, different types of carbohydrates, micronutrients naturally found in foods vs supplements, industrial trans-fats, food preparation and handling techniques and dietary patterns and cancer, in order to implement safe cancer prevention strategies. PMID- 27557385 TI - Proposals for the prevention of lung cancer in the health system of Mexico. AB - The management of lung cancer is challenging. However, nowadays the main goal is to achieve a significant overall survival accompanied by a good quality of life. Because smoking is associated with up to 71% of cancer deaths, the first policy that should be established is one that promotes strategies for healthy lifestyles by providing information about lung cancer, risk factors, protection factors, and precautionary data. Furthermore, an effective screening method that would allow early diagnosis should be established. Following diagnosis, the patient should be genotyped to identify predisposing mutations to give personalized medicine to the patient. The health system policies should include information that affects the health of the population and simultaneously allows for early diagnoses, resulting in a higher survival rate. PMID- 27557386 TI - Prostate cancer. AB - Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer. PMID- 27557387 TI - Oropharyngeal cancer: an emergent disease? AB - Oropharyngeal cancer incidence has recently increased, thereby attracting public attention. Akin to other malignancies of the upper aerodigestive tract, it has been attributed to the carcinogenic effects of tobacco and alcohol use. However, recent evidence shows that a substantial increase in the disease is attributable to the effects of human papillomavirus (HPV). Marked progress has been made in relation to the knowledge of molecular and genetic mechanisms involved in the genesis and progression of these cancers. This has led to the development of new and promising therapies of a more specific and less toxic nature that have prolonged life and improved its quality. However, these therapies have failed to significantly increase the proportion of patients who are cured. To decrease the mortality associated with these neoplasms, it is necessary to adopt public health measures aimed at prevention and early diagnosis. PMID- 27557388 TI - Advances in the diagnosis and treatment of acute and chronic leukemia in Mexico. AB - In the last 60 years, there have been substantial advances regarding the diagnosis and treatment of patients with acute and chronic leukemia in Mexico. Immunologic and molecular classifications of these diseases have improved both diagnosis and therapeutic capabilities. Although the pace of diagnostic and therapeutic advances has been slower compared with developed countries, Mexico is at the forefront among developing countries. Supporting research in these fields is expected to enhance the generation of new knowledge and improve the care of patients suffering from these diseases. PMID- 27557389 TI - Advances in the diagnosis and control of lymphomas. AB - Lymphoproliferative disorders have increased in last decades. Immunohistochemistry analysis is required to categorize them in different clinical entities, as has been stablished by WHO. Advances in imaging have set the PET-CT as a standard staging procedure in most cases. Knowledge of the biology of these malignancies has allowed therapeutic advances with different approaches, including development of monoclonal antibodies, conjugated antibodies, immunomodulatory agents, as well as inhibition of specific pathways. Although new drugs are promising, the cost-benefit impact requires to be evaluated in pharmacoeconomic clinical trials. PMID- 27557390 TI - Epidemiological overview, advances in diagnosis, prevention, treatment and management of epithelial ovarian cancer in Mexico. AB - The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease. PMID- 27557391 TI - The importance of registries in cancer control. AB - Cancer is one of the major causes of morbidity and mortality in the world, with 14.1 million new cases and 8.2 million deaths annually. A marked disparity exists between developed countries and developing countries, with 57% of new cases and 65% of deaths in 2012 occurring in developing countries. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow cancer estimations for different geographic areas. Our objective is to perform a review of different types of registries and their role in the control of cancer. These types of registries are lacking in developing countries. In Central and South America, only 6% of the population is included in cancer registries versus 83% in North America. It is necessary to increase the coverage of cancer registries to obtain more reliable data that will more appropriately guide control programs. PMID- 27557392 TI - Integrated oncology and palliative care: five years experience at the National Cancer Institute of Mexico. AB - Under the national plan for addressing cancer, prevention and detection play important roles. However, the cost of treatments and late diagnosis represent a significant burden on health services. At the National Cancer Institute, more than half of patients present with tumors in advanced stages, and approximately 10% of patients seen for the first time exhibit terminal-stage malignancies, where there are no feasible cancer treatment options, and the patients are instead admitted to the hospital exclusively for palliative symptomatic management. In 2010, the National Cancer Plan began implementing a model of integrative management of palliative care in oncology that has gradually come to include symptomatic palliative care, involving ambulatory, distant and hospitalized management of patients with cancer, in its final stages and, more recently, in earlier stages. PMID- 27557393 TI - Challenges in the development and implementation of the National Comprehensive Cancer Control Program in Mexico. AB - Chronic noncommunicable diseases (NCDs), including cancer, have become the leading cause of human morbidity and mortality. In Mexico, cancer is the third leading cause of death, with a high incidence among the economically active population, a high proportion of advanced stages at diagnosis and limited care coverage for patients. However, no public policy aimed at managing this important public health problem has been developed and implemented to date. This manuscript describes the first interinstitutional proposal of a National Program for Cancer Control, considering the known risk factors, early detection, treatment, palliative care and patient rehabilitation. This manuscript also outlines a series of thoughts on the difficulties and needs that the Mexican health system faces in achieving the main objectives of the program: to decrease the incidence of cancer, to increase survival and to improve the quality of life for this group of patients. PMID- 27557394 TI - Interaction of Biologically Active Flavins inside Bile Salt Aggregates: Molecular Level Investigation. AB - In this work we have studied the photophysics of biologically active flavin molecule lumichrome (LCM) in different bile-salt aggregates. With alteration of the functional groups of the bile salts, the photophysics of confined fluorophore is largely affected and shows difference in their spectral behavior. This study also reveals the selective prototropic species of LCM present in bile salt aggregates. In the presence of the bile salt aggregates, LCM molecule shows excitation and emission wavelength-dependent emission properties, indicating switch over of the structural change of different prototropic form of the LCM molecule. The observation of higher rotational relaxation time in NaDC aggregates compared to NaTC aggregates clearly reflects that NaDC aggregates are more rigid due to its greater hydrophobicity and large in size, which is capable to bind the guest molecule more into their nanoconfined medium. Moreover, due to less acidic nature, NaDC aggregates have more ability to accept hydrogen bond from the LCM molecule and show the selective formation of isoalloxazine N10 anion (A1 monoanionic form) of LCM. PMID- 27557396 TI - Levator ani muscle injuries associated with vaginal vacuum assisted delivery determined by 3/4D transperineal ultrasound. AB - OBJECTIVES: To determine the rate of pelvic floor trauma, levator ani muscle (LAM) avulsion as well as the mean difference in levator hiatus area, after normal vaginal deliveries (NVD) and vacuum assisted deliveries (VD), assessed with three-dimensional transperineal ultrasound (3D-TpUS). MATERIALS AND METHODS: Prospective observational study with 151 nulliparous women with NVD or VD at >=37 weeks between 9-2012 and 6-2013. 3D-TpUS was performed six months after every patient's delivery, during which LAM, anteroposterior diameter, transverse diameter and levator hiatus area were assessed. RESULTS: A total of 146 nulliparous were studied, comprising 73 NVD and 73 VD. No differences in obstetric, intrapartum or neonatal characteristics were observed between study groups, with the following exceptions: maternal age (28.1 +/- 5.4 versus 30.4 +/- 5.5; p = 0.008, OR = 1.1) and episiotomy rate (35.6% versus 97.3%; p = 0.011, OR = 4.3). LAM avulsion rate was 9.6% in NVD versus 34.2% in VD (p = 0.001, OR 3.99), while levator hiatus area at rest was 16.5 +/- 3.2 versus 18.2 +/- 3.9 (p = 0.016). CONCLUSIONS: Vacuum assisted deliveries present a higher rate of LAM avulsion, as well as a greater increase in levator hiatal area than in NVD. PMID- 27557397 TI - Forms of interdisciplinarity in four sport science research centres in Europe. AB - Interdisciplinarity is often presented as a significant element of sport science. We present here the results of an investigation conducted in four European Sport Science Research Centres applying interdisciplinarity. Four main dimensions, that we have called "forms", have been investigated. The "scientific", "organisational", "academic" and "societal" forms cover a wide range of activities run by these Centres. We have compared their situations using indicators. Globally they present quite similar combinations of forms, with dominant roles in the construction of interdisciplinarity played by the organisational and societal forms. The scientific form is never quite supported by an epistemological setting and the academic form, mostly characterised by the position of the university, plays an influential role when it is hostile to that kind of research. Following Klein classification, all of them remain at a multidisciplinary stage, one of them exploring interdisciplinary tracks in some research projects. The development of a common culture and a curiosity regarding disciplines other than its own is a key factor for a sustainable situation, as is the capacity to secure long-term financial resources, often linked to a high academic recognition for the director(s). PMID- 27557395 TI - Mixed-methods analysis of internalized stigma correlates in poorly adherent individuals with bipolar disorder. AB - BACKGROUND: Internalized stigma, which occurs when stigmatized individuals accept society's assessment and incorporate this assessment into their sense of self, is prevalent in individuals with bipolar disorder (BD). This study explored the correlates of internalized stigma in a research sample of patients with BD who were poorly adherent to their medications. METHODS: Both quantitative and qualitative analyses were performed. Scores of 115 individuals with BD on the Internalized Stigma of Mental Illness (ISMI) scale were correlated with scores on the General Self-Efficacy (GSE) Scale, Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS). Regression was run for GSE (dependent variable) and ISMI (independent variable). In-depth qualitative interviews were conducted on a representative subsample (N=21). RESULTS: Internalized stigma levels were moderately high. Internalized stigma and self-efficacy correlated, and internalized stigma related to self-efficacy after adjusting for demographic variables (age, gender, years of education), comorbidities, and symptom severity (BPRS and MADRS). Internalized stigma was also associated with the BD symptoms of depression, anxiety, guilt feelings, suspiciousness, and hallucinogenic behaviors. No association was found with mania. CONCLUSIONS: Because internalized stigma has strong psychosocial and psychiatric symptom associations, it is recommended that clinicians address both societal stigma and internalized stigma. Strategies such as cognitive-behavioral therapy may help modify BD patients' internalized stigma. PMID- 27557398 TI - Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model. AB - Microneedle arrays have been developed to deliver a range of biomolecules including vaccines into the skin. These microneedles have been designed with a wide range of geometries and arrangements within an array. However, little is known about the effect of the geometry on the potency of the induced immune response. The aim of this study was to develop a computational model to predict the optimal design of the microneedles and their arrangement within an array. The three-dimensional finite element model described the diffusion and kinetics in the skin following antigen delivery with a microneedle array. The results revealed an optimum distance between microneedles based on the number of activated antigen presenting cells, which was assumed to be related to the induced immune response. This optimum depends on the delivered dose. In addition, the microneedle length affects the number of cells that will be involved in either the epidermis or dermis. By contrast, the radius at the base of the microneedle and release rate only minimally influenced the number of cells that were activated. The model revealed the importance of various geometric parameters to enhance the induced immune response. The model can be developed further to determine the optimal design of an array by adjusting its various parameters to a specific situation. PMID- 27557399 TI - Development of a liquid formulation of poorly water-soluble isosteviol sodium using the co-solvent technology. AB - An intravenously injectable liquid formulation of the poorly water-soluble isosteviol sodium (ISVNa) that has a great clinical potential for cardiovascular diseases was developed using the co-solvent technology. The pH and composition of the co-solvent were optimized to obtain a stable liquid formulation (termed as STVNa) based on saline at pH 10.0 containing 25% (v/v) of ethanol and 20% (v/v) of propylene glycol. STVNa was physicochemically stable upon storage for more than 3 months under various conditions. In vitro studies showed that STVNa did not induce hemolytic effects up to 9.1% (v/v) after 3 h of incubation and it was cytocompatible up to 50 MUg/mL in H2C9 cells. Furthermore, STVNa showed acceptable safety and pharmacokinetic parameters comparable with those of ISVNa in saline (dissolved at 60 degrees C) upon i.v. injection in Wistar rats. Overall, the results demonstrated that STVNa is a promising formulation of ISVNa for clinical translation. PMID- 27557400 TI - Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis. AB - Importance: Transthyretin cardiac amyloidosis (also known as ATTR cardiac amyloidosis) is an increasingly recognized cause of heart failure with preserved ejection fraction. In single-center studies, technetium 99m pyrophosphate (Tc 99m PYP) cardiac imaging noninvasively detects ATTR cardiac amyloidosis, but the accuracy of this technique in a multicenter study and the association of Tc 99m PYP myocardial uptake with survival are unknown. Objective: To assess Tc 99m PYP cardiac imaging as a diagnostic tool for ATTR cardiac amyloidosis and its association with survival in a multicenter study. Design, Setting, and Participants: Retrospective cohort study performed at 3 academic specialty centers for cardiac amyloidosis in the United States in which 229 participants were evaluated for cardiac amyloidosis and also underwent Tc 99m PYP cardiac imaging. The date of analysis and final confirmation from the statistician was May 4, 2016. Exposure: Tc 99m PYP cardiac imaging for detection of ATTR cardiac amyloidosis. Main Outcomes and Measures: Retention of Tc 99m PYP in the heart was assessed using both a semiquantitative visual score (range, 0 [no uptake] to 3 [uptake greater than bone]) and a quantitative heart to contralateral (H/CL) ratio. The H/CL ratio was calculated as total counts in a region of interest over the heart divided by background counts in an identical size region of interest over the contralateral chest. The outcome measured was time to death after Tc 99m PYP imaging. Results: Tc 99m PYP imaging of 171 participants (121 with ATTR cardiac amyloidosis and 50 with non-ATTR cardiac amyloidosis [34 with AL amyloidosis and 16 with nonamyloid heart failure with preserved ejection fraction]; 86% male; median [IQR] age, 73 years [65-79 years]) demonstrated 91% sensitivity and 92% specificity for detecting ATTR cardiac amyloidosis with an area under the curve of 0.960 (95% CI, 0.930-0.981). Univariable and multivariable Cox proportional hazards regression analyses among participants with ATTR cardiac amyloidosis showed that an H/CL ratio of 1.6 or greater predicted worse survival (hazard ratio, 3.911 [95% CI, 1.155-13.247]; P = .03 for univariable analysis and 7.913 [95% CI, 1.679-37.296]; P = .01 for multivariable analysis). In Kaplan-Meier analysis over a 5-year follow-up period, survival was significantly worse if the H/CL ratio was 1.6 or greater rather than less than 1.6 (log-rank P = .02). Conclusions and Relevance: In this multicenter study, Tc 99m PYP cardiac imaging conferred a high level of sensitivity and specificity for differentiation of patients with ATTR cardiac amyloidosis (irrespective of genotype) from patients with AL cardiac amyloidosis and patients with nonamyloid heart failure with preserved ejection fraction. An H/CL ratio of 1.6 or greater was associated with worse survival among patients with ATTR cardiac amyloidosis. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, Tc 99m PYP may be of diagnostic and prognostic importance. PMID- 27557401 TI - Quantification of Single-Kidney Function and Volume in Living Kidney Donors Using Dynamic Contrast-Enhanced MRI. AB - OBJECTIVE: The objective of our study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) can detect differences and potential adaption in single kidney parenchymal volume, blood flow, glomerular filtration rate (GFR), and filtration fraction in the remaining kidney of healthy donors compared with nondonors. Further, we evaluated the agreement in donor GFRs measured using DCE MRI versus serum clearance of iohexol. SUBJECTS AND METHODS: Twenty living kidney donors and 20 healthy control subjects underwent DCE-MRI and iohexol GFR. Renal parenchymal volume was assessed from maximum-signal-intensity maps. Single-kidney MRI measurements of blood flow and GFR were derived from parenchymal signal intensity-time curves fitted to a two-compartment filtration model. The Student t test, Pearson correlation coefficient, mean differences, and limits of agreement were applied to analyze MRI measurements between groups and agreement with iohexol GFR. RESULTS: MRI findings showed significantly higher blood flow (difference in mean values of donors vs control subjects, 54%; p = 0.001), GFR (78%, p < 0.0001), and renal parenchymal volume (65%, p < 0.0001) in the single kidney of donors compared with the single kidney of healthy control subjects. In the donors, a proportional increase in blood flow and GFR resulted in a comparable filtration fraction, as was observed in the control subjects. Significant correlations were found between MRI-derived GFR and parenchymal volume (p < 0.0016) as well as with iohexol GFR (p < 0.0001). The mean difference between MRI-derived GFR and iohexol GFR was 14.0 mL/min, and the limits of agreement between MRI-derived GFR and iohexol GFR were -24.1 and 52.1 mL/min. CONCLUSION: DCE-MRI-derived values for single-kidney function and volume in kidney donors were significantly higher than those in control subjects and suggest a future potential benefit of DCE-MRI for diagnostic and prognostic structural and functional assessments in living kidney donors. PMID- 27557402 TI - Clusters of Painful Blue Papules. PMID- 27557403 TI - Energetic 4,4'-Oxybis[3,3'-(1-hydroxytetrazolyl)]furazan and Its Salts. AB - Energetic compounds that incorporate multiple nitrogen-rich heterocycles are of great interest for high-density energetic materials. A facile synthetic strategy to combine an oxy bridge and furazan groups, as well as tetrazole-ols, into a molecule (5) was found. Some energetic salts based on 5 were prepared by neutralization. All of the compounds were fully characterized. Additionally, the structure of 7 has been elucidated by single-crystal XRD analysis. Physicochemical and energetic properties were also studied; these show that these newly designed energetic salts exhibit good thermal stabilities. Hydroxylammonium salt (6) has a detonation performance and sensitivities comparable with those of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). PMID- 27557404 TI - Broadband pH-Sensing Organic Transistors with Polymeric Sensing Layers Featuring Liquid Crystal Microdomains Encapsulated by Di-Block Copolymer Chains. AB - We report broadband pH-sensing organic field-effect transistors (OFETs) with the polymer-dispersed liquid crystal (PDLC) sensing layers. The PDLC layers are prepared by spin-coating using ethanol solutions containing 4-cyano-4'-pentyl biphenyl (5CB) and a diblock copolymer (PAA-b-PCBOA) that consists of LC-philic block [poly(4-cyano-biphenyl-4-oxyundecyl acrylate) (PCBOA)] and acrylic acid block [poly(acrylic acid) (PAA)]. The spin-coated sensing layers feature of 5CB microdomains (<5 MUm) encapsulated by the PAA-b-PCBOA polymer chains. The resulting LC-integrated-OFETs (PDLC-i-OFETs) can detect precisely and reproducibly a wide range of pH with only small amounts (10-40 MUL) of analyte solutions in both static and dynamic perfusion modes. The positive drain current change is measured for acidic solutions (pH < 7), whereas basic solutions (pH > 7) result in the negative change of drain current. The drain current trend in the present PDLC-i-OFET devices is explained by the shrinking-expanding mechanism of the PAA chains in the diblock copolymer layers. PMID- 27557405 TI - Validity of the Physical Activity Questionnaires IPAQ-SF and GPAQ for Cancer Survivors: Insights from a Spanish Cohort. AB - Regular physical activity (PA) decreases mortality risk in survivors of breast and colorectal cancer. Such impacts of exercise have prompted initiatives designed both to promote and adequately monitor PA in cancer survivors. This study examines the validity of 2 widely used self-report methods for PA determination, the International Physical Activity Questionnaire short version (IPAQ-SF) and Global Physical Activity Questionnaire (GPAQ). Both instruments were compared with the triaxial accelerometry (Actigraph) method as an objective reference standard. Study participants were 204 cancer survivors (both sexes, aged 18-79 years). Compared with accelerometry, both questionnaires significantly overestimated PA levels (across all intensities) and underestimated physical inactivity levels. No differences were detected between the 2 questionnaires except for a shorter inactivity time estimated by GPAQ (p=0.001). The Bland and Altman method confirmed that both questionnaires overestimated all PA levels. Receiver operating characteristic (ROC) analysis classified IPAQ and GPAQ as fair and poor predictors, respectively, of the proportions of survivors fulfilling international PA recommendations (>=150 min.week-1 of moderate-vigorous PA). IPAQ SF showed a higher sensitivity but lower specificity than GPAQ. Our data do not support the use of IPAQ-SF or GPAQ to determine PA or inactivity levels in cancer survivors. PMID- 27557406 TI - Jump Training in Youth Soccer Players: Effects of Haltere Type Handheld Loading. AB - The aim of this study was to compare the effects of a jump training program, with or without haltere type handheld loading, on maximal intensity exercise performance. Youth soccer players (12.1+/-2.2 y) were assigned to either a jump training group (JG, n=21), a jump training group plus haltere type handheld loading (LJG, n=21), or a control group following only soccer training (CG, n=21). Athletes were evaluated for maximal-intensity performance measures before and after 6 weeks of training, during an in-season training period. The CG achieved a significant change in maximal kicking velocity only (ES=0.11-0.20). Both jump training groups improved in right leg (ES=0.28-0.45) and left leg horizontal countermovement jump with arms (ES=0.32-0.47), horizontal countermovement jump with arms (ES=0.28-0.37), vertical countermovement jump with arms (ES=0.26), 20-cm drop jump reactive strength index (ES=0.20-0.37), and maximal kicking velocity (ES=0.27-0.34). Nevertheless, compared to the CG, only the LJG exhibited greater improvements in all performance tests. Therefore, haltere type handheld loading further enhances performance adaptations during jump training in youth soccer players. PMID- 27557407 TI - The Effect of Water Temperature during Cold-Water Immersion on Recovery from Exercise-Induced Muscle Damage. AB - This study investigated the effects of 5 and 15 degrees C cold-water immersion on recovery from exercise resulting in exercise-induced muscle damage. 42 college aged men performed 5*20 drop-jumps and were randomly allocated into one of 3 groups: (1) 5 degrees C; (2) 15 degrees C; or (3) control. After exercise, individuals from the cold-water immersion groups had their lower limbs immerged in iced water for 20 min. Isometric knee extensor torque, countermovement jump, muscle soreness, and creatine kinase were measured before, immediately after, 24, 48, 72, 96 and 168 h post-exercise. There was no between-group difference in isometric strength recovery (p=0.73). However, countermovement jump recovered quicker in cold-water immersion groups compared to control group (p<0.05). Countermovement jump returned to baseline after 72 h in 15 degrees C, 5 degrees C group recovered after 96 h and control did not recovered at any time point measured. Also, creatine kinase returned to baseline at 72 h and remained stable for all remaining measurements for 15 degrees C group, whereas remained elevated past 168 h in both 5 degrees C and control groups. There was a trend toward lower muscle soreness (p=0.06) in 15 degrees C group compared to control at 24 h post exercise. The result suggests that cold-water immersion promote recovery of stretch-shortening cycle performance, but not influence the recovery of maximal contractile force. Immersion at warmer temperature may be more effective than colder temperatures promoting recovery from strenuous exercise. PMID- 27557408 TI - DNA Damage Assessment in Zebrafish Embryos Exposed to Monceren((r)) 250 SC Fungicide Using the Alkaline Comet Assay. AB - Monceren 250 SC is a commercial fungicide with the active ingredient 1-(4 chlorobenzyl)-1-(cyclopentyl)-3-phenylurea, also known as pencycuron. This compound inhibits the growth of fungi as Rhizoctonia solani that invades potato, rice, and cotton or as Pellicularia spp, which contaminates lettuce and tomato crops. In this study, we assessed genotoxicity or DNA damage by the alkaline comet assay in zebrafish blastula-stage embryos exposed to 250 to 1250 MUg/mL of the Monceren fungicide or to Bleomycin (0.25 MUg/mL) used as a positive control. Additionally, survival and spontaneous movement were monitored in embryos after exposure to different concentrations of fungicide. DNA damage was evaluated using three genotoxicity parameters of the alkaline comet assay: tail length, tail moment, and tail intensity. We found that Monceren 250 SC fungicide induces DNA damage, as shown by significant increases in the three genotoxicity parameters in zebrafish embryos compared with control embryos nonexposed to Monceren. Tail intensity was the more accurate parameter to evaluate genotoxicity levels in zebrafish embryos. At 48 h after exposure to the fungicide, the survival rate of larvae-embryos was reduced to 40-45%. This study shows that the Monceren 250 SC fungicide exerts genotoxic effects in zebrafish during early stages of development. PMID- 27557410 TI - Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens. AB - CONTEXT: - Fine-needle aspiration of thyroid nodules is a reliable diagnostic method to determine the nature of thyroid nodules. Nonetheless, indeterminate cytology diagnoses remain a diagnostic challenge. The development of multiplex molecular techniques and the identification of genetic alterations associated with different follicular cell-derived cancers in the thyroid have led to the introduction of several commercially available tests. OBJECTIVE: - To summarize the most common commercially available molecular testing in thyroid cancer, focusing on the technical features and test performance validation. DATA SOURCES: - Peer-reviewed original articles, review articles, and published conference abstracts were reviewed to analyze the advantages and limitations of the most common tests used in the evaluation of thyroid needle aspirations. CONCLUSIONS: - The most common tests available include the Afirma Gene Expression Classifier, ThyGenX, and ThyroSeq. The excellent negative predictive value (NPV) of the Afirma test allows it to be used as a "rule out" test. ThyGenX analyzes a panel of DNA mutations and RNA translocation fusion markers to assess the risk of malignancy with good NPV and positive predictive value. ThyroSeq is a next generation sequencing-based gene mutation and fusion test that has been reported to have the best NPV and positive predictive value combined, suggesting that it can be used as a "rule in" and "rule out" test. Molecular testing of cytology specimens from thyroid nodules has the potential to play a major role in the evaluation of indeterminate thyroid lesions. PMID- 27557411 TI - The State of Cell Blocks and Ancillary Testing: Past, Present, and Future. AB - Cell blocks are an integral part of cytology, but their utility is recognized probably more now than ever before, largely owing to the significant role they play in ancillary testing, particularly molecular diagnostics. Modifications to improve the cell block method initially introduced more than a century ago have been made over the years. Though their value is acknowledged and they are widely used across laboratories, cell block preparations are not standardized and results of ancillary testing performed on them are inconsistent. This article reviews the state of cell blocks-summarizes the more common, currently available and used methods and their corresponding advantages and shortcomings, outlines the role of alternative techniques (eg, smears), and proposes methods to optimize results. PMID- 27557409 TI - Ultraperformance convergence chromatography-high resolution tandem mass spectrometry for lipid biomarker profiling and identification. AB - Lipids represent biologically ubiquitous and highly dynamic molecules in terms of abundance and structural diversity. Whereas the potential for lipids to inform on disease/injury is promising, their unique characteristics make detection and identification of lipids from biological samples analytically demanding. We report the use of ultraperformance convergence chromatography (UPC2 ), a variant of supercritical fluid chromatography, coupled to high-resolution, data independent tandem mass spectrometry for characterization of total lipid extracts from mouse lung tissue. The UPC2 platform resulted in lipid class separation and when combined with orthogonal column chemistries yielded chromatographic separation of intra-class species based on acyl chain hydrophobicity. Moreover, the combined approach of using UPC2 with orthogonal column chemistries, accurate mass measurements, time-aligned low- and high-collision energy total ion chromatograms, and positive and negative ion mode product ion spectra correlation allowed for confident lipid identification. Of great interest was the identification of differentially expressed ceramides that were elevated 24 h post whole thorax lung irradiation. The identification of lipids that were elevated 24 h post-irradiation signifies a unique opportunity to investigate early mechanisms of action prior to the onset of clinical symptoms in the whole thorax lung irradiation mouse model. PMID- 27557412 TI - Update on the College of American Pathologists Experience With High-Risk Human Papillomavirus Proficiency Testing for Cytology. AB - CONTEXT: - Since 2008, the College of American Pathologists has provided the human papillomavirus for cytology laboratories (CHPV) proficiency testing program to help laboratories meet the requirements of the Clinical Laboratory Improvement Amendments of 1988. OBJECTIVES: - To provide an update on trends in proficiency testing performance in the College of American Pathologists CHPV program during the 4-year period from 2011 through 2014 and to compare those trends with the preceding first 3 years of the program. DESIGN: - Responses of laboratories participating in the CHPV program from 2011 through 2014 were analyzed using a nonlinear mixed model to compare different combinations of testing medium and platform. RESULTS: - In total, 818 laboratories participated in the CHPV program at least once during the 4 years, with participation increasing during the study period. Concordance of participant responses with the target result was more than 98% (38 280 of 38 892). Overall performance with all 3 testing media-ThinPrep (Hologic, Bedford, Massachusetts), SurePath (Becton, Dickinson and Company, Franklin Lakes, New Jersey), or Digene (Qiagen, Valencia, California)-was equivalent (P = .51), and all 4 US Food and Drug Administration (FDA)-approved platforms-Hybrid Capture 2 (Qiagen), Cervista (Hologic), Aptima (Hologic), and cobas (Roche Molecular Systems, Pleasanton, California)-outperformed laboratory developed tests, unspecified commercial kits, and other (noncommercial) methods in ThinPrep medium (P < .001). However, certain off-label combinations of platform and medium, most notably Cervista with SurePath, demonstrated suboptimal performance (P < .001). CONCLUSIONS: - Laboratories demonstrated proficiency in using various combinations of testing media and platforms offered in the CHPV program, with statistically significant performance differences in certain combinations. These observations may be relevant in the current discussions about FDA oversight of laboratory-developed tests. PMID- 27557413 TI - Autopsy and Postmortem Studies Are Concordant: Pathology of Zika Virus Infection Is Neurotropic in Fetuses and Infants With Microcephaly Following Transplacental Transmission. AB - CONTEXT: -Pathology studies have been important in concluding that Zika virus infection occurring in pregnant women can result in vertical transmission of the agent from mother to fetus. Fetal and infant autopsies have provided crucial direct evidence that Zika virus can infect an unborn child, resulting in microcephaly, other malformations, and, in some cases, death. OBJECTIVE: -To better understand the etiologic role and mechanism(s) of Zika virus in causing birth defects such as microcephaly, this communication analyzes the spectrum of clinical and autopsy studies reported from fetuses and infants who developed intrauterine Zika virus infection, and compares these findings with experimental data related to Zika virus infection. DESIGN: -Retrospective analysis of reported clinical, autopsy, pathology, and related postmortem studies from 9 fetuses and infants with intrauterine Zika virus infection and microcephaly. RESULTS: -All fetuses and infants examined demonstrated an overlapping spectrum of gross and microscopic neuropathologic abnormalities. Direct cytopathic effects of infection by the Zika virus were confined to the brain; in cases where other organs were evaluated, no direct viral effects were identified. CONCLUSIONS: -There is concordance of the spectrum of brain damage, reinforcing previous data indicating that the Zika virus has a strong predilection for cells of the fetal central nervous system following vertical transmission. The occurrence of additional congenital abnormalities suggests that intrauterine brain damage from Zika virus interferes with normal fetal development, resulting in fetal akinesia. Experimental in vitro and in vivo studies of Zika virus infection corroborate the human autopsy findings of neural specificity. PMID- 27557414 TI - Financial Performance of Rural Medicare ACOs. AB - PURPOSE: The Centers for Medicare & Medicaid Services (CMS) has facilitated the development of Medicare accountable care organizations (ACOs), mostly through the Medicare Shared Savings Program (MSSP). To inform the operation of the Center for Medicare & Medicaid Innovation's (CMMI) ACO programs, we assess the financial performance of rural ACOs based on different levels of rural presence. METHODS: We used the 2014 performance data for Medicare ACOs to examine the financial performance of rural ACOs with different levels of rural presence: exclusively rural, mostly rural, and mixed rural/metropolitan. RESULTS: Of the ACOs reporting performance data, we identified 97 ACOs with a measurable rural presence. We found that successful rural ACO financial performance is associated with the ACO's organizational type (eg, physician-based) and that 8 of the 11 rural ACOs participating in the Advanced Payment Program (APP) garnered savings for Medicare. Unlike previous work, we did not find an association between ACO size or experience and rural ACO financial performance. CONCLUSIONS: Our findings suggest that rural ACO financial success is likely associated with factors unique to rural environments. Given the emphasis CMS has placed on rural ACO development, further research to identify these factors is warranted. PMID- 27557416 TI - Editorial. PMID- 27557417 TI - Erratum. PMID- 27557418 TI - Emestrins: Anti-Cryptococcus Epipolythiodioxopiperazines from Podospora australis. AB - Eleven emestrin-type epipolythiodioxopiperazines, including four new compounds, emestrins H-K (1-4), were isolated from the crude extracts of two strains of the coprophilous fungus Podospora australis. The structures of 1-4 were established primarily by analysis of NMR data, and the absolute configuration of C-6 in 1 was independently assigned using the modified Mosher method. Four of the known emestrins obtained (emestrins C-E and MPC1001C) were found to selectively inhibit the growth of Cryptococcus neoformans. These results also represent the first report of chemistry from any strain of P. australis. PMID- 27557415 TI - Sugar Influx Sensing by the Phosphotransferase System of Escherichia coli. AB - The phosphotransferase system (PTS) plays a pivotal role in the uptake of multiple sugars in Escherichia coli and many other bacteria. In the cell, individual sugar-specific PTS branches are interconnected through a series of phosphotransfer reactions, thus creating a global network that not only phosphorylates incoming sugars but also regulates a number of cellular processes. Despite the apparent importance of the PTS network in bacterial physiology, the holistic function of the network in the cell remains unclear. Here we used Forster resonance energy transfer (FRET) to investigate the PTS network in E. coli, including the dynamics of protein interactions and the processing of different stimuli and their transmission to the chemotaxis pathway. Our results demonstrate that despite the seeming complexity of the cellular PTS network, its core part operates in a strikingly simple way, sensing the overall influx of PTS sugars irrespective of the sugar identity and distributing this information equally through all studied branches of the network. Moreover, it also integrates several other specific metabolic inputs. The integrated output of the PTS network is then transmitted linearly to the chemotaxis pathway, in stark contrast to the amplification of conventional chemotactic stimuli. Finally, we observe that default uptake through the uninduced PTS network correlates well with the quality of the carbon source, apparently representing an optimal regulatory strategy. PMID- 27557419 TI - Selective inhibition of human carbonic anhydrase IX in Xenopus oocytes and MDA-MB 231 breast cancer cells. AB - Human carbonic anhydrase IX (CA IX) is overexpressed in the most aggressive and invasive tumors. Therefore, CA IX has become the promising antitumor drug target. Three inhibitors have been shown to selectively and with picomolar affinity inhibit human recombinant CA IX. Their inhibitory potencies were determined for the CA IX, CA II, CA IV and CA XII in Xenopus oocytes and MDA-MB-231 cancer cells. The inhibition IC50 value of microelectrode-monitored intracellular and extracellular acidification reached 15 nM for CA IX, but with no effect on CA II expressed in Xenopus oocytes. Results were confirmed by mass spectrometric gas analysis of lysed oocytes, when an inhibitory effect on CA IX catalytic activity was found after the injection of 1 nM VD11-4-2. Moreover, VD11-4-2 inhibited CA activity in MDA-MB-231 cancer cells at nanomolar concentrations. This combination of high selectivity and potency renders VD11-4-2, an auspicious therapeutic drug for target-specific tumor therapy. PMID- 27557420 TI - Inborn Errors of Metabolism in Elderly Adults. PMID- 27557421 TI - Intrauterine growth restriction impairs right ventricular response to hypoxia in adult male rats. AB - BACKGROUND: Intrauterine growth restriction (IUGR) predisposes to cardiovascular diseases in adulthood. The mechanisms of this phenomenon remain cryptic. We hypothesized that heart mitochondria in IUGR-born adult rats are more sensitive to acute hypoxia which translates into dysfunctional cardiac response to hypoxic stress. METHODS: Adult IUGR-born male rats (the offspring of dams fed with calories-restricted diet during pregnancy) were exposed to acute hypoxic stress with echocardiographic assessment of cardiac function. In parallel, mitochondrial respiration in organelles isolated from left ventricle (LV) and right ventricle (RV) was tested in normoxic and anoxic conditions. The extent of post-anoxic inhibition of mitochondrial respiration and cardiac function was compared with controls, non-IUGR rats. RESULTS: Compared with controls, in the IUGR rats hypoxia significantly reduced only RV contractility, evidenced by decreased fractional shortening, functional area of contraction, and tricuspid annular plane systolic excursion. In isolated mitochondria, anoxic challenge inhibited respiratory chain in both groups of rats. However, compared with controls, the extent of anoxic mitochondrial depression was significantly greater in IUGR-born rats, but only in the organelles isolated from RV. CONCLUSIONS: In adult IUGR born rats, mitochondria from RV are hypersensitive to oxygen deprivation and this translates into maladaptive RV cardiac response to acute hypoxia. PMID- 27557422 TI - A Molecular Basis for Innovation in Drug Excipients. AB - Excipients are ubiquitous in drug formulation, ensuring that active ingredient drugs are properly released on dosing, retain their properties over time, and are palatable, among other roles. Despite their crucial roles, surprisingly little is known about their systemic availability and activities on molecular targets. Here we review key excipient properties, introduce a public-accessible database that enumerates and categorizes them, and sketch a strategy for exploring their possible direct actions on molecular targets. PMID- 27557423 TI - Efficient sequential and parallel algorithms for finding edit distance based motifs. AB - BACKGROUND: Motif search is an important step in extracting meaningful patterns from biological data. The general problem of motif search is intractable and there is a pressing need to develop efficient, exact and approximation algorithms to solve this problem. In this paper, we present several novel, exact, sequential and parallel algorithms for solving the (l,d) Edit-distance-based Motif Search (EMS) problem: given two integers l,d and n biological strings, find all strings of length l that appear in each input string with atmost d errors of types substitution, insertion and deletion. METHODS: One popular technique to solve the problem is to explore for each input string the set of all possible l-mers that belong to the d-neighborhood of any substring of the input string and output those which are common for all input strings. We introduce a novel and provably efficient neighborhood exploration technique. We show that it is enough to consider the candidates in neighborhood which are at a distance exactly d. We compactly represent these candidate motifs using wildcard characters and efficiently explore them with very few repetitions. Our sequential algorithm uses a trie based data structure to efficiently store and sort the candidate motifs. Our parallel algorithm in a multi-core shared memory setting uses arrays for storing and a novel modification of radix-sort for sorting the candidate motifs. RESULTS: The algorithms for EMS are customarily evaluated on several challenging instances such as (8,1), (12,2), (16,3), (20,4), and so on. The best previously known algorithm, EMS1, is sequential and in estimated 3 days solves up to instance (16,3). Our sequential algorithms are more than 20 times faster on (16,3). On other hard instances such as (9,2), (11,3), (13,4), our algorithms are much faster. Our parallel algorithm has more than 600 % scaling performance while using 16 threads. CONCLUSIONS: Our algorithms have pushed up the state-of-the-art of EMS solvers and we believe that the techniques introduced in this paper are also applicable to other motif search problems such as Planted Motif Search (PMS) and Simple Motif Search (SMS). PMID- 27557424 TI - Wreaking Reproductive Havoc One Chemical at a Time. PMID- 27557425 TI - Lentigo maligna - anatomic location as a potential risk factor for recurrences after non-surgical treatment. AB - BACKGROUND: A higher incidence of lentigo maligna (LM) recurrences on the nose was previously observed in our cohort after non-surgical treatment. OBJECTIVES: To determine histological parameters that might be related to the previously observed higher incidence of LM recurrences on the nose after non-surgical treatment. METHODS: We randomly selected 22 surgical specimens of LM on the nose and 22 on the cheek. Histopathological analysis was performed on haematoxylin and eosin stained and microphthalmia transcription factor immunohistochemically stained slides. The number of pilosebaceous units (PSU) per mm, maximum depth of atypical melanocytes along the skin appendages and maximum depth of the PSU itself were determined. RESULTS: The nose had a significantly higher density of PSU than the cheek. The atypical melanocytes extended deeper along the PSU on the nose with a mean (SD) depth of 1.29 mm (0.48) vs. a mean depth of 0.72 mm (0.30) on the cheek (P < 0.001). The maximum depth of the PSU on the nose was greater than on the cheek, mean (SD) depth of 2.28 mm (0.41) vs. 1.65 mm (0.82) (P = 0.003). CONCLUSIONS: The higher recurrence risk of LM on the nose after non surgical treatment that we previously observed in our cohort is most likely based on a higher density of atypical melanocytes and also their deeper extension into the follicles. These results shed more light on our previous findings and learn that anatomical location is relevant for the risk of recurrence of LM after non surgical treatment. PMID- 27557426 TI - Sertraline as an Additional Treatment for Cholestatic Pruritus in Children. AB - OBJECTIVES: Pruritus is a severe symptom accompanying chronic cholestasis. It can be debilitating and difficult to control. In children, first-line treatments are ursodeoxycholic acid and rifampicin. Refractory pruritus may require invasive therapies including liver transplantation. Clinical trials based on small samples of adult patients suggest that serotonin reuptake inhibitors can improve pruritus in cholestatic or uremic disease. We performed a prospective, multicenter study to assess efficiency and safety of the serotonin reuptake inhibitor sertraline in treating children with refractory cholestatic pruritus. METHODS: Twenty children experiencing refractory cholestatic pruritus related to Alagille syndrome or progressive familial intrahepatic cholestasis were included from 4 centers between 2007 and 2014, and treated with sertraline at a starting dose of 1 mg . kg . day and thereafter individually adapted up to 4 mg . kg . day. Before and after 3 months with therapy, pruritus was assessed using a visual itching scale graded on 10 points, a skin scratch marks score and a sleeping impairment score. RESULTS: Sertraline was prescribed at a median daily dose of 2.2 mg . kg . day. After 3 months, pruritus improved in 14 out of 20 treated patients, and the median itching score decreased significantly from 8/10 (5-10) to 5/10 (2-10). Likewise, skin scratch marks and sleep quality improved in 9 of these 14 patients. Nonsevere adverse events were reported in 6 children, leading to treatment discontinuation in 3. CONCLUSION: Our data suggest that sertraline may constitute a useful drug in the management of refractory cholestatic pruritus in children. PMID- 27557427 TI - The Intragastric Pressure Measurement: A Novel Method to Assess Gastric Accommodation in Functional Dyspepsia Children. AB - BACKGROUND: Impaired gastric accommodation (GA) is proposed as a main pathophysiological mechanism for functional dyspepsia (FD). At present, the gastric barostat is the criterion standard to measure GA. Hence, this procedure is invasive and it may alter gastric physiology. Recently, we proposed the measurement of intragastric pressure (IGP) by means of high-resolution manometry during nutrient intake as a potential alternative for assessing GA in adults. OBJECTIVES: Our aim was first to study the feasibility of the IGP measurement with nutrient tolerance in children with FD and second to compare these results with young healthy adults. METHODS: A high-resolution manometry probe and a feeding tube were positioned in the proximal stomach. The IGP was measured before and during intragastric infusion of a nutrient drink (ND, 300 kcal, 60 mL/min). Subjects were asked to score their satiation and epigastric symptoms. The test ended when the subjects scored maximal satiation. RESULTS: A total of 15 healthy volunteers (HVs, 21.7 +/- 4.7 years, 21.1 +/- 0.3 kg/m) and 17 patients with FD (14.4 +/- 0.7 years, 19.6 +/- 0.7 kg/m) participated. Patients with FD experienced mainly from postprandial fullness (86%), epigastric pain (71%), and bloating (62%). In both groups, intragastric infusion of ND induced a drop in IGP (area above the IGP curve FD: -15.5 +/- 3.5 mmHg vs HVs: -18.0 +/- 8.7 mmHg; P = 0.57). Patients showed impaired nutrient tolerance compared with HVs (587.6 +/- 80.2 vs 936 +/- 66.2 kcal; P = 0.003). All patients and HVs tolerated the catheters and could finalize the study. CONCLUSIONS: The measurement of IGP during intragastric ND infusion was well tolerated in children. Nutrient tolerance was reduced in children with FD compared with HVs. In the future, this may be a useful tool to assess GA accommodation and nutrient tolerance in children. PMID- 27557428 TI - Nutritional Status in Short Stature Children Is Related to Both Ghrelin and Insulin-like Growth Factor I Concentrations. AB - OBJECTIVES: Ghrelin plays an important role in the growth processes in children. In addition, it regulates appetite. The aim of the study was to assess ghrelin and insulin-like growth factor type I (IGF-I) concentrations in children with idiopathic short stature, dependent on nutritional status. METHODS: The study group included 116 children, ages 10.6 +/- 3.5 years (mean +/- standard deviation), with idiopathic short stature (height <-2.0 standard deviation scores [SDS], maximal growth hormone [GH] secretion during 2 GH-stimulating tests->10 ng/mL). In each child, fasting ghrelin, IGF-I, insulin-like growth factor binding protein 3 (IGFBP-3), glucose, insulin, lipids, leptin, adiponectin, and resistin concentrations were assessed. The IGF-I/IGFBP-3 molar ratio was calculated to determine the IGF-I bioavailability. According to body mass index SDS calculated for height age, the children were divided into 3 groups: poorly nourished (thin), normal, and obese. The control group consisted of 19 healthy children, ages 11.0 +/- 3.5 years, with normal body weight and height. RESULTS: Ghrelin concentration was significantly higher in short, thin children than in short, obese children (1458.3 +/- 798.5 vs 917.2 +/- 303.0 pg/mL; P < 0.005). In turn, IGF-I/IGFBP-3 molar ratio was significantly lower in short, thin children than in short, obese children (0.16 +/- 0.06 vs 0.28 +/- 0.15; P < 0.005). CONCLUSIONS: In short, thin children, despite elevated ghrelin production, the low IGF-I concentration is observed, probably due to undernutrition and worse IGF-I formation. In short, normal-weight children and in short, obese ones, ghrelin and IGF-I production is normal, and it seems that mechanisms responsible for their short stature are other than low IGF-I. PMID- 27557429 TI - Machine learning-based 3-D geometry reconstruction and modeling of aortic valve deformation using 3-D computed tomography images. AB - To conduct a patient-specific computational modeling of the aortic valve, 3-D aortic valve anatomic geometries of an individual patient need to be reconstructed from clinical 3-D cardiac images. Currently, most of computational studies involve manual heart valve geometry reconstruction and manual finite element (FE) model generation, which is both time-consuming and prone to human errors. A seamless computational modeling framework, which can automate this process based on machine learning algorithms, is desirable, as it can not only eliminate human errors and ensure the consistency of the modeling results but also allow fast feedback to clinicians and permits a future population-based probabilistic analysis of large patient cohorts. In this study, we developed a novel computational modeling method to automatically reconstruct the 3-D geometries of the aortic valve from computed tomographic images. The reconstructed valve geometries have built-in mesh correspondence, which bridges harmonically for the consequent FE modeling. The proposed method was evaluated by comparing the reconstructed geometries from 10 patients with those manually created by human experts, and a mean discrepancy of 0.69 mm was obtained. Based on these reconstructed geometries, FE models of valve leaflets were developed, and aortic valve closure from end systole to middiastole was simulated for 7 patients and validated by comparing the deformed geometries with those manually created by human experts, and a mean discrepancy of 1.57 mm was obtained. The proposed method offers great potential to streamline the computational modeling process and enables the development of a preoperative planning system for aortic valve disease diagnosis and treatment. PMID- 27557430 TI - Why won't they sit with me? An exploratory investigation of stereotyped cues, social exclusion, and the P3b. AB - The importance of understanding how we anticipate and prepare for being socially excluded is underscored by the numerous adverse mental and physical consequences of social rejection. In this study, we adapted a social exclusion paradigm, the Lunchroom task, to investigate the use of social context cues in the formation of social outcome expectations as indexed by the P3b, an ERP component associated with attention orientation and context updating. In this task, Black and White participants were presented with either neutral or stereotyped cues prior to being exposed to simulated inclusion versus exclusion outcome scenarios. Black participants showed evidence of (1) a significantly reduced P3b response to exclusions preceded by stereotyped cues relative to neutral cue-related exclusions and (2) a marginally significant increase in the P3b response to inclusions relative to exclusions when both were preceded by stereotyped cues. Both of these findings suggest a key role for the use of social cues in the formation of outcome expectations. In line with our hypothesis that the random intermixing of inclusion and exclusion outcomes would prevent formation of outcome expectations when coupled with the absence of self-relevant cues, no overall P3b modulations were observed among a comparison group of White participants. PMID- 27557431 TI - Evaluation for citation metrics and peer reviewer acknowledgments. AB - This editorial discusses the indexing systems that include the Journal of Chiropractic Education, reflects on the increased international participation in chiropractic education scholarly meetings and peer review, and acknowledges the editorial board and peer reviewers for the journal. PMID- 27557432 TI - Selection and applicability of quenching agents for the analysis of polar iodinated disinfection byproducts. AB - Iodide is widely present in drinking water sources as well as wastewater effluents. Chlorination and chloramination are the most commonly used disinfection methods. During chlorination or chloramination of drinking water/wastewater effluents, iodide may be oxidized to hypoiodous acid, which may further react with organic matter to form iodinated disinfection byproducts (DBPs). Recently, several new polar iodinated DBPs have been identified in drinking water as well as chlorinated wastewater effluents, and they have drawn increasing concerns due to their high toxicity. In DBPs studies, the selection of an appropriate quenching agent is critical to prevent further formation or any decomposition of DBPs during the holding time between sample collection and analysis. A previous study reported the applicability of different quenching agents for the analysis of various categories of chlorinated and brominated DBPs. But the applicability of quenching agents for the analysis of polar iodinated DBPs has not been reported. In this study, four different quenching agents (sodium sulfite, sodium thiosulfate, ascorbic acid and sodium borohydride) were tested for their suitability for the analysis of polar iodinated DBPs, and ascorbic acid was selected as the suitable quenching agent. Furthermore, it was found that ascorbic acid was applicable for the analysis of polar iodinated DBPs under the quenching agent doses of 0-0.42 mmol/L (stoichiometric amounts equivalent to 0-30 mg/L Cl2), contact times within 24 h, and pHs in the range of 6-8. Therefore, ascorbic acid was a widely applicable quenching agent for the analysis of polar iodinated DBPs under various conditions. PMID- 27557433 TI - Impact of three task demand factors on simulated unmanned system intelligence, surveillance, and reconnaissance operations. AB - The present study investigated how three task demand factors influenced performance, subjective workload and stress of novice intelligence, surveillance, and reconnaissance operators within a simulation of an unmanned ground vehicle. Manipulations were task type, dual-tasking and event rate. Participants were required to discriminate human targets within a street scene from a direct video feed (threat detection [TD] task) and detect changes in symbols presented in a map display (change detection [CD] task). Dual-tasking elevated workload and distress, and impaired performance for both tasks. However, with increasing event rate, CD task deteriorated, but TD improved. Thus, standard workload models provide a better guide to evaluating the demands of abstract symbols than to processing realistic human characters. Assessment of stress and workload may be especially important in the design and evaluation of systems in which human character critical signals must be detected in video images. Practitioner Summary: This experiment assessed subjective workload and stress during threat and CD tasks performed alone and in combination. Results indicated an increase in event rate led to significant improvements in performance during TD, but decrements during CD, yet both had associated increases in workload and engagement. PMID- 27557434 TI - Predominant prevalence of human rotaviruses with the G1P[8] and G8P[8] genotypes with a short RNA profile in 2013 and 2014 in Sukhothai and Phetchaboon provinces, Thailand. AB - Of 2,754 stool specimens collected from children with acute gastroenteritis during 2013-2014 in Sukhothai and Phetchaboon provinces, Thailand, 666 (24.2%) were positive for rotavirus A (RVA) in polyacrylamide gel electrophoresis (PAGE). The G and P types of all RVA-positive specimens were determined by semi-nested RT PCR. G1P[8] (56.5%) was most prevalent, followed by G2P[4] (22.1%). Unusual G8P[8] human RVAs (HuRVAs) were detected at a high frequency (20.0%). Interestingly, 171 of the 376 G1P[8] HuRVAs and all of the 133 G8P[8] HuRVAs showed a short RNA pattern in PAGE. Thus, it was shown that the properties of HuRVAs have been markedly unusual in recent years in Thailand. J. Med. Virol. 89:615-620, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27557435 TI - Peripapillary Suprachoroidal Cavitation, Parapapillary Gamma Zone and Optic Disc Rotation Due to the Biomechanics of the Optic Nerve Dura Mater. PMID- 27557436 TI - Author Response: Peripapillary Suprachoroidal Cavitation, Parapapillary Gamma Zone and Optic Disc Rotation Due to the Biomechanics of the Optic Nerve Dura Mater. PMID- 27557437 TI - Neutral-Density Filters Are Not a Patch on Occlusion. PMID- 27557439 TI - Imaging follow-up study of acute rhinosinusitis. AB - OBJECTIVES/HYPOTHESIS: To evaluate with imaging the course of acute rhinosinusitis (ARS) and the associations between paranasal imaging results, symptoms, bony anatomic variations, and culture-proven bacterial ARS. STUDY DESIGN: Inception cohort study with 50 conscripts with ARS. METHODS: During a single ARS episode, we collected symptoms daily and took sequential cone-beam computed tomography (CBCT) scans of the paranasal sinuses of the same patients 2 to 3, 5 to 6 and 9 to 10 days after the onset of symptoms. Culture-proven bacterial ARS was verified with maxillary sinus aspiration and bacterial culture at 9 to 10 days. RESULTS: At 2 to 3 days, 38% of the patients had major abnormalities, 42% had minor abnormalities in their paranasal sinuses, and 68% had an occluded ostiomeatal complex (OMC). At 5 to 6 days and 9 to 10 days, these proportions remained essentially the same. At 2 to 3 days, patients with bacterial ARS had slightly higher CBCT scores than those without bacterial ARS. Later, the CBCT and symptom scores gradually increased in patients with bacterial ARS and decreased in those without bacterial ARS. The CBCT and symptom scores had only a weak correlation (rs = 0.36), and anatomic variations were not related to development of bacterial ARS. CONCLUSIONS: Paranasal mucosal abnormalities and occlusion of the OMC do not develop gradually during ARS, but are present when symptoms begin and remain fairly constant in most patients both with and without bacterial ARS. This indicates that the spread of the disease process to the paranasal sinuses and obstruction of the OMC may not be etiological factors in the development of bacterial ARS. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1965 1970, 2016. PMID- 27557440 TI - Combinatorial Strategies for Synthesis and Characterization of Alloy Microstructures over Large Compositional Ranges. AB - The exploration of new alloys with desirable properties has been a long-standing challenge in materials science because of the complex relationship between composition and microstructure. In this Research Article, we demonstrate a combinatorial strategy for the exploration of composition dependence of microstructure. This strategy is comprised of alloy library synthesis followed by high-throughput microstructure characterization. As an example, we synthesized a ternary Au-Cu-Si composition library containing over 1000 individual alloys using combinatorial sputtering. We subsequently melted and resolidified the entire library at controlled cooling rates. We used scanning optical microscopy and X ray diffraction mapping to explore trends in phase formation and microstructural length scale with composition across the library. The integration of combinatorial synthesis with parallelizable analysis methods provides a efficient method for examining vast compositional ranges. The availability of microstructures from this vast composition space not only facilitates design of new alloys by controlling effects of composition on phase selection, phase sequence, length scale, and overall morphology, but also will be instrumental in understanding the complex process of microstructure formation in alloys. PMID- 27557441 TI - Serial trichoscopy vs. modified hair pull test for monitoring the disease activity and treatment response of localized alopecia areata. PMID- 27557438 TI - Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review. AB - Importance: Stem cell therapy is a promising treatment strategy for patients with heart failure, which accounts for more than 10% of deaths in the United States annually. Despite more than a decade of research, further investigation is still needed to determine whether stem cell regenerative therapy is an effective treatment strategy and can be routinely implemented in clinical practice. Objective: To describe the progress in cardiac stem cell regenerative therapy using adult stem cells and to highlight the merits and limitations of clinical trials performed to date. Evidence Review: Information for this review was obtained through a search of PubMed and the Cochrane database for English language studies published between January 1, 2000, and July 26, 2016. Twenty nine randomized clinical trials and 7 systematic reviews and meta-analyses were included in this review. Findings: Although adult stem cells were once believed to have the ability to create new heart tissue, preclinical studies suggest that these cells release cardioprotective paracrine factors that activate endogenous pathways, leading to myocardial repair. Subsequent randomized clinical trials, most of which used autologous bone marrow mononuclear cells, have found only a modest benefit in patients receiving stem cell therapy. The lack of a significant benefit may result from variations in trial methods, discrepancies in reporting, and an overreliance on surrogate end points. Conclusions and Relevance: Although stem cell therapy for cardiovascular disease is not yet ready for routine clinical application, significant progress continues to be made. Physicians should be aware of the current status of this treatment so that they can better inform their patients who may be in search of alternative therapies. PMID- 27557442 TI - A Closer Look at Rural-Urban Health Disparities: Associations Between Obesity and Rurality Vary by Geospatial and Sociodemographic Factors. AB - BACKGROUND: Obesity affects over one-third of older adults in the United States. Both aging and obesity contribute to an increased risk for chronic disease, early mortality, and additional health care utilization. Obesity rates are higher in rural areas than in urban areas, although findings are mixed. The objectives of this study are to assess potential nonlinearity in the association between rurality and obesity, and to evaluate the potential for socioeconomic status and geographic area to moderate the associations between rurality and obesity. METHODS: Using a representative sample of adults aged 65 and above from the Behavioral Risk Factor Surveillance System, obesity (BMI >= 30 kg/m2 ) was modeled against the primary exposure of rural-urban status, as measured by the Index of Relative Rurality. Binary logistic regression models were used to estimate the odds of obesity by rurality both as a continuous variable and by decile of rurality. Models were then stratified by per-capita income and state to assess potential moderation by these factors. RESULTS: The prevalence of obesity in older adults was highest in intermediate rurality areas (OR in rurality decile #5 1.134, 95% CI: 1.086-1.184) and lowest in the most rural and most urban areas. Obesity was highest in low- and middle-income areas, regardless of rural-urban status. In high-income areas, obesity among older adults was highest in areas of intermediate rurality and lowest in the most rural areas (OR 0.726, 95% CI: 0.606 0.870) and more urban areas, showing a J-shaped association. There were substantial differences in the associations between rurality and obesity in older adults among states. CONCLUSION: Associations between rurality and obesity varied by degree of rurality, socioeconomic status, and geography. Therefore, traditional "one-size-fits-all" approaches to reducing rural-urban health disparities in older adults may be more effective if tailored to the area specific rural-urban gradients in health. PMID- 27557443 TI - [Pilot Study of the Feasibility of a Short Biofeedback Treatment of Chronic Headache in the Outpatient Care System]. AB - Introduction: Although biofeedback has been shown to be an effective treatment of tension-type headache and migraine, it has not been well implemented in the outpatient care system yet. Central aims of this randomized controlled pilot study were to examine the feasibility and implementation of a short biofeedback treatment of chronic headache in the outpatient care system, to estimate standardized effect sizes for treatment outcome, and to investigate the influence of expectancies on treatment outcomes. Methods: In this pilot study, the patients (N=18) were diagnosed according to the criteria defined by the International Headache Society and randomized afterwards. Patients received 8-11 sessions of biofeedback (depending on the indication: Electromyography biofeedback, Vasoconstriction-/Vasodilatation training or a combination of both). Outcome assessments took place before and after the biofeedback treatment via questionnaires. Hedges' g was computed based on change scores of treatment expectancies, session performance (patients and therapists), headache-specific self-efficacy (Headache Management Self-efficacy Scale-Short form), headache related variables (Pain Disability Index, German Pain Coping Questionnaire) and comorbid strain (Hospital Anxiety and Depression Scale). Pearson-correlations were calculated for the relations of change scores. Results: Effect sizes for most of the assessed expectancies and coping were high (g=0.94-1.45). Improvements in the willingness to practice and disability in everyday life were moderate (g=0.40-0.51). The correlations between patients' expectancies and disability or coping were medium (r=- 0,42 - 0.41). Results showed a moderate negative correlation between the patient-rated session performance and depression (r=-0.33). Discussion and Conclusion: The short biofeedback treatment showed a good feasibility and implementation in the outpatient care system, with pilot results indicating effectiveness. The documented associations between patient rated and therapist-rated expectancies and the treatment outcome emphasize the importance of the assessment of expectancies. PMID- 27557445 TI - How to build a human. AB - The genes that control the development of specific tissues and organs in human embryos have been identified. PMID- 27557444 TI - Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors. AB - Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction. PMID- 27557447 TI - Hybrid Dendrimers of PPI(core)-PAMAM(shell): A Molecular Dynamics Simulation Study. AB - The structural properties of hybrid dendrimers PPI(core)-PAMAM(shell) for application in drug delivery are studied by coarse-grained molecular dynamics simulation, and their capacity to encapsulate drug guest molecules such as pyrene is investigated by changing the core (PPI) in the PPI-PAMAM hybrids. For this purpose, a coarse-grained model for PPI dendrimer is developed and is used to predict the structural properties as a function of PPI core size, such as the size of hybrid dendrimers, the depth of water penetration, the extent of back folding of their chain terminals, the size and distribution of created cavities, and asphericity. The results show that the location of pyrene in the interior structure of the hybrids is independent of PPI core size and the branching chains create a barrier against the penetrating molecules in the shell of PPI. Then, by adding the PAMAM to the surface of PPI, this barrier is removed, and this will enhance the encapsulation capacity of the hybrid. PMID- 27557446 TI - An integrative transcriptomic atlas of organogenesis in human embryos. AB - Human organogenesis is when severe developmental abnormalities commonly originate. However, understanding this critical embryonic phase has relied upon inference from patient phenotypes and assumptions from in vitro stem cell models and non-human vertebrates. We report an integrated transcriptomic atlas of human organogenesis. By lineage-guided principal components analysis, we uncover novel relatedness of particular developmental genes across different organs and tissues and identified unique transcriptional codes which correctly predicted the cause of many congenital disorders. By inference, our model pinpoints co-enriched genes as new causes of developmental disorders such as cleft palate and congenital heart disease. The data revealed more than 6000 novel transcripts, over 90% of which fulfil criteria as long non-coding RNAs correlated with the protein-coding genome over megabase distances. Taken together, we have uncovered cryptic transcriptional programs used by the human embryo and established a new resource for the molecular understanding of human organogenesis and its associated disorders. PMID- 27557448 TI - Sampling Serum in Patients With Vitiligo to Measure Disease Activity in the Skin. PMID- 27557449 TI - Re: Oelke et al. Unravelling detrusor underactivity: Development of a bladder outlet resistance-bladder contractility nomogram for adult male patients with lower urinary tract symptoms and Letter-to-the-Editor by Alison Bray and Michael Drinnan. PMID- 27557450 TI - Mismatch Between Proximal Rod Contouring and Proximal Junctional Angle: A Predisposed Risk Factor for Proximal Junctional Kyphosis in Degenerative Scoliosis. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate whether the mismatch between proximal junctional angle (PJA) and the proximal rod contouring contributed to the occurrence of postoperative proximal junctional kyphosis (PJK) in degenerative scoliosis. SUMMARY OF BACKGROUND DATA: PJK is one of the complications in the treatment of degenerative scoliosis, the postoperative PI-LL mismatch and the increased rod stiffness are supposed to be the etiology of PJK. However, the impact of rod contouring on PJK has not been fully illustrated. METHODS: A retrospective study was performed on 27 consecutive degenerative scoliosis patients (three males and 24 females) who underwent corrective surgery with more than 2-year follow-up. Radiographic parameters included proximal rod contouring angle (PRCA) and PJA at the three time-points. The subjects were divided into two groups: PJK group and non-PJK group with the definition of PJK as a PJA more than 10 degrees . The mismatch between PRCA and post-op PJA, defined as the difference between PRCA and postop PJA of more than 5 degrees , was then compared with PJK and non-PJK group. RESULTS: The patients' mean age was 60.48 +/- 6.47 years old with a mean Cobb angle of 40.89 +/- 14.33 degrees . Twelve patients, with a mean PJA of 18.67 +/- 5.31 degrees at the last followup, were stratified into the PJK group, while the remaining 15 patients, with a mean PJA of 5.33 +/- 2.47, were placed into the non-PJK group. A significant difference in the mismatch between post-op PJA and PRCA was observed between PJK and non-PJK group (8.83 +/- 5.07 degrees vs. 4.07 +/- 2.91 degrees , P = 0.005). Meanwhile the difference of mismatch between preop PJA and PRCA showed no statistical significance (5.16 +/- 4.24 degrees vs. 3.00 +/- 2.48 degrees , P = 0.109). CONCLUSION: Mismatch between rod contouring and postoperative proximal spinal curve may be a predisposed risk factor for PJK in degenerative scoliosis. LEVEL OF EVIDENCE: 4. PMID- 27557451 TI - Diagnostic Accuracy of Somatosensory Evoked Potentials in Evaluating New Neurological Deficits After Posterior Cervical Fusions. AB - STUDY DESIGN: This study examined the diagnostic accuracy of significant changes of somatosensory evoked potentials (SSEPs) to evaluate and predict postoperative neurological deficits after posterior cervical fusions (PCF). Eight hundred forty six eligible patients underwent PCF at the University of Pittsburgh Medical Center (UPMC), from 2010 to 2012. OBJECTIVE: To assess the specificity and sensitivity of intraoperative monitoring in predicting postoperative neurological deficits during PCF. SUMMARY OF BACKGROUND DATA: We calculated the predictive value, including sensitivity and specificity, of changes in SSEPs to identify neurological deficits postoperatively. We used a receiver operating characteristic (ROC) curve with SSEP categories as cutoff values to further evaluate the diagnostic accuracy of change in SSEPs and postoperative neurological deficit. METHODS: All patients had preposition baselines and continuous SSEP monitoring throughout the surgery. Statistical analysis was completed using SPSS version 22 (IBM Corp., Armonk, NY). RESULTS: Age and sex did not influence outcomes. Obesity affected patient outcome. The SSEP categories of significant changes and loss of responses resulted in a sensitivity/specificity of 0.30/0.96 and 0.16/0.98, respectively. The receiver operating characteristic curve has an area under the curve for significant change in/loss of SSEPs of 0.62/0.65 with a 95% confidence interval of 0.525 to 0.714/0.509 to 0.797. CONCLUSION: Significant SSEP changes during PCF are a very specific but poorly sensitive indicator of postoperative neurological deficits. The odds ratio for significant changes in SSEPs and loss of waveforms was 9.80 and 11.82, respectively, with a 95% confidence interval of 4.695 to 20.46 and 4.45 to 31.41, respectively. LEVEL OF EVIDENCE: 1. PMID- 27557452 TI - Validation of Using Claims Data to Measure Safety of Lumbar Fusion Surgery. AB - STUDY DESIGN: Retrospective analysis of patients undergoing elective lumbar fusion operations, comparing rates of repeat spine surgery based on method of ascertainment. OBJECTIVE: We report the accuracy of a claims-based approach for reporting repeat surgery compared with medical records abstraction as the "gold standard." SUMMARY OF BACKGROUND DATA: Previous studies have reported the validity of a claims-based algorithm for grouping patients by surgical indication and classifying operative features, but their accuracy in measuring surgical quality indicators has not been widely examined. METHODS: We identified a subset of patients undergoing elective lumbar fusion operations at a single institution from 1996 to 2011, excluding those with spinal fracture, spinal cord injury, or cancer. From the medical record we abstracted the incidence of repeat spine operation or rehospitalization at 1 year. We cross-classified each event record with its corresponding value derived from claims. The sensitivity and specificity of the claims-based approach were calculated for reoperation within 30, 90, and 365 days, and all-cause hospital readmission within 30 days. RESULTS: Medical records linked to claims data were obtained for 520 patients undergoing elective lumbar fusion. Reoperation rates based on chart review were 1.0%, 1.3%, 3.6%, compared with 0.8%, 1.7%, and 3.8% based on the final claims methods at 30, 90, and 365 days, respectively. The claims-based algorithm had sensitivities of 80.0%, 100%, and 94.1% and specificities of 100%, 99.6%, 99.2% for repeat surgery within 30, 90, and 365 days, respectively. The sensitivity for all-cause readmission was 50%. CONCLUSION: Health care quality improvement efforts often rely on administrative data to report surgical safety. We found that claims-based ascertainment of safety at a single institution was very accurate. However, accuracy depended on careful attention to the timing of outcomes, as well as the definitions and coding of repeat surgery, including how orthopedic device removal codes are classified. LEVEL OF EVIDENCE: 3. PMID- 27557453 TI - Cost-benefit analysis of the intraoperative parathyroid hormone assay in primary hyperparathyroidism. AB - BACKGROUND: The purpose of this study was to evaluate the usefulness of the routine intraoperative intact parathyroid hormone (IOPTH) assay, the role of unilateral and bilateral cervical exploration and of preoperative imaging, and to do a cost-benefit analysis in parathyroidectomy for primary hyperparathyroidism. METHODS: Two hundred sixty-four patients who underwent operations between January 2000 and March 2015 were retrospectively divided into 2 groups. RESULTS: Group A (IOPTH) was composed of 64 patients. Ultrasonography and technetium-99m-sestamibi (MIBI) identified the adenoma in 38 cases. Bilateral exploration was performed in 43 patients; of which 2 failures occurred. The IOPTH false-negative rate was 18.4%. The average cost was ?1297.30. Group B (without IOPTH) was composed of 200 patients. Ultrasonography and MIBI identified the adenoma in 113 cases. Bilateral exploration was performed in 129 patients; of which 2 failures occurred. The average cost was ?618.75. CONCLUSION: The IOPTH assay should be used only in few selected cases because of its high cost. The experience of the team is essential to obtain a high cure rate. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 241 246, 2017. PMID- 27557454 TI - Catastrophizing, rumination, and reappraisal prospectively predict adolescent PTSD symptom onset following a terrorist attack. AB - BACKGROUND: Disruptions in emotion regulation are a transdiagnostic risk factor for psychopathology. However, scant research has examined whether emotion regulation strategies are related to the onset of posttraumatic stress disorder (PTSD) symptoms among youths exposed to trauma. We investigated whether pretrauma emotion regulation strategies prospectively predicted PTSD symptom onset after the 2013 Boston Marathon terrorist attack among adolescents and whether these associations were moderated by the degree of exposure to media coverage of the attack. METHODS: A sample of 78 Boston-area adolescents (mean age = 16.72 years, 65% female) who previously participated in studies assessing emotion regulation and psychopathology were recruited following the terrorist attack. Within 4 weeks of the attack, we assessed self-reported PTSD symptoms and attack-related media exposure via an online survey. We examined the association of pretrauma emotion regulation strategies with PTSD symptom onset after adjustment for pretrauma internalizing symptoms and violence exposure. RESULTS: Greater pretrauma engagement in rumination predicted onset of PTSD symptoms following the attack. Adolescents who engaged in catastrophizing also had greater PTSD symptoms postattack, but only when exposed to high levels of media coverage of the attacks; the same pattern was observed for adolescents who engaged in low levels of cognitive reappraisal. CONCLUSIONS: Engagement in specific emotion regulation strategies prior to a traumatic event predicts the onset of PTSD symptoms among youths exposed to trauma, extending transdiagnostic models of emotion regulation to encompass trauma-related psychopathology in children and adolescents. PMID- 27557455 TI - A fast and sensitive UHPLC-MS/MS method for the determination of N butylscopolamine in human plasma: application in a bioequivalence study. AB - We have developed and validated a fast and sensitive ultra high-performance liquid chromatography with positive ion electrospray ionization tandem mass spectrometry method for determining N-butylscopolamine levels in human plasma using propranolol as an internal standard. The acquisition was set up in the multiple reaction monitoring mode with the transitions m/z 360.3 -> 138.0 for N butylscopolamine and m/z 260.2 -> 116.1 for IS. This method uses a liquid-liquid extraction process with dichloromethane. The analyte and IS were chromatographed on a C18 , 50 * 2.1 mm, 1.7 MUm column through isocratic elution with acetonitrile-5 mm ammonium acetate (adjusted to pH 3.0 with formic acid). The method was linear in the 1-1000 pg/mL range for N-butylscopolamine and was selective, precise, accurate and robust. The validated method was successfully applied to perform a bioequivalence study of the reference (Buscopan(r) , from Boehringer Ingelheim) and the test sample coated-tablet formulations (from Foundation for Popular Remedy), both containing 10 mg of N-butylscopolamine bromide administered as a single dose. Using 58 healthy volunteers and accounting for the high intra-individual variability confirmed by statistical calculations (38%), the two formulations were considered bioequivalent because the rate and extent of absorption (within 80-125% interval), satisfying international requirements. PMID- 27557456 TI - Airborne foliar transfer of PM bound heavy metals in Cassia siamea: A less common route of heavy metal accumulation. AB - In order to investigate possible foliar transfer of toxic heavy metals, concentrations of Cd, Pb, and Fe were measured in samples of: Cassia siamea leaves (a common tree) Cassia siamea foliar dust, nearby road dust, and soil (Cassia siamea tree roots) at six different sites in/around the Bilaspur industrial area and a control site on the university campus. Bilaspur is located in a subtropical central Indian region. The enrichment factor (EF) values of Pb and Cd, when derived using the crustal and measured soil Fe data as reference, indicated significant anthropogenic contributions to Pb and Cd regional pollution. Based on correlation analysis and scanning electron microscopy (SEM) observations, it was evident that Pb and Cd in foliar part of Cassia siamea were largely from airborne sources. The SEM studies of leaf confirmed that leaf morphology (epidermis, trichome, and stomata) of Cassia siamea helped accumulate the toxic metals from deposited particulate matter (PM). There is a line of evidence that the leaf of Cassia siamea was able to entrap PM in respirable suspended particulate matter (RSPM) range (i.e., both in fine and coarse fractions). The overall results of this study suggest that Cassia siamea can be a potential plant species to control the pollution of PM and PM-bound metals (Pb and Cd) in affected areas. PMID- 27557457 TI - Evaluation of aggregate microstructures following natural regeneration in bauxite residue as characterized by synchrotron-based X-ray micro-computed tomography. AB - Bauxite residue often has poor physical conditions which impede plant growth. Native plant encroachment on a bauxite residue disposal area in Central China reveals that natural regeneration may improve its physicochemical properties. Residue samples collected from three different disposal ages were assessed to evaluate residue micromorphology and three-dimensional (3D) aggregate microstructure under natural regeneration. The residue aggregates in different disposal ages were divided in two sections: macro-aggregate (2-1mm) and micro aggregate (0.25-0.05mm). Residue aggregate micromorphology was determined by scanning electron microscope and energy dispersive X-ray spectroscopy, and the residue aggregate microstructure was determined by synchrotron-based X-ray micro computed tomography (SR-MUCT) and image analysis techniques. Natural regeneration may improve residue aggregate stability and form a stable aggregate structure. Calcium content increased whilst sodium content decreased significantly on the surface of residue aggregates. Under natural soil-forming processes bauxite residue porosity, specific surface area, average length of paths, and average tortuosity of paths all significantly increased. This demonstrated that natural regeneration may stimulate the formation of stable aggregate structure in residues. Further understanding should focus on particle interaction forces and agglomeration mechanisms with the addition of external ameliorations. PMID- 27557458 TI - Detection of modiolar proximity through bipolar impedance measurements. AB - OBJECTIVES: To test the hypothesis that bipolar electrical impedance measurements in perimodiolar cochlear implants (CIs) may be used to differentiate between perimodiolar insertion technique favoring proximity to the modiolus or lateral wall. STUDY DESIGN AND METHODS: Bipolar impedances are a measure of electrical resistance between pairs of electrode contacts in a CI. Stimulation is through biphasic pulses at fixed frequency. Impedance measurements were made in real time through sequential sampling of electrode pairs. Perimodiolar electrodes were inserted in temporal bones using one of two techniques: 1) In the standard insertion technique (SIT), the electrode array slides along the lateral wall during insertion. 2) In the Advance Off Stylet (Cochlear Ltd. Sydney) technique (AOS), the electrode maintains modiolar contact throughout the insertion process. A set of 22 insertions were performed in temporal bone specimens using perimodiolar electrode arrays with both AOS and SIT. Buffered saline was used as a substitute for natural perilymph based on similar electrical conductivity properties. Impedance with and without stylet removal were recorded with a 30 second sampling window at final insertion depth. RESULTS: There is a significant difference in bipolar impedance measures between AOS and SIT, with impedances rising in measurements with stylet removal. Evaluation was based on two-sided analysis of variance considering technique and electrode with P < 0.025. CONCLUSION: Bipolar electrical impedance can be used to detect relative motion toward the modiolus inside the cochlea. This detection method has the potential to optimize intraoperative placement of perimodiolar electrode arrays during implantation. We anticipate that this will result in lower excitation thresholds and improved hearing outcome. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:1413-1419, 2017. PMID- 27557459 TI - Implementation of a Tranexamic Acid Protocol to Reduce Blood Loss During Cranial Vault Remodeling for Craniosynostosis. AB - OBJECTIVE: Pediatric cranial vault remodeling for repair of craniosynostosis is associated with significant blood loss and transfusion requirements. Beginning in 2011, the authors evaluated the impact tranexamic acid (TXA) on blood loss and blood product transfusion for children less than 15 months of age undergoing primary surgical repair of nonsyndromic single suture craniosynostosis. METHODS: Following institutional review board approval, the authors performed a retrospective study of all children undergoing surgical correction of craniosynostosis at Oregon Health & Science University from 2005 to 2015. All available records were reviewed, and patient data were collected from the time of preoperative evaluation until discharge, comparing patient and clinical variables before and after the implementation of perioperative TXA. RESULTS: Of a total of 259 patients with craniosynostosis, 187 had nonsyndromic single-suture involvement; 69 of these patients (36.9%) received TXA. A single surgical team (AAK and NRS) performed all operations. Median age at the time of surgery was 8.1 months (interquartile range [IQR] of 6.0-9.8 months). The TXA group had a significant reduction in estimated intraoperative blood loss (26 mL/kg versus 36 mL/kg, P <0.001), cell saver volume transfused 6 mL/kg versus 10 mL/kg, P <0.001), red cell transfusion volume (32 mL/kg versus 42 mL/kg, P <0.001), exposure to plasma transfusion (0% versus 24% P <0.001), exposure to cryoprecipitate transfusion (0% versus 16%, P <0.001), and exposure to platelet transfusion (0% versus 7.6% P = 0.03). Despite reduced red cell transfusion, the TXA-treated patients exhibited similar postoperative hematocrits (30.4 versus 30.3 P = 0.906) to those not treated with TXA. Use of TXA was associated with reduced length of stay (4 days IQR 3-4 versus 4 days IQR 4-5, P <0.001) and reduced postoperative output from surgically placed drains (181 mL versus 311 mL P <0.001). There was no difference in postoperative complications between groups and no deaths in either group. CONCLUSIONS: The introduction of TXA for nonsyndromic single-suture synostosis repair at our institution has significantly reduced blood loss and blood product and plasma transfusion during and following primary cranial vault remodeling for single suture craniosynostosis. Postoperative hematocrit was similar in the TXA-treated and untreated groups despite reduced red cell transfusion in the treated group. In addition, TXA use in this population has eliminated the need for plasma transfusion, and is associated with a shorter hospital stay. No difference in postoperative complications was observed. Our data provide support for further investigation of TXA treatment to improve clinical outcomes in children undergoing pediatric cranial vault remodeling. PMID- 27557460 TI - Relative Projective Location of Three Bottom Apexes of Petrous Bone on Skull. AB - The complex anatomy of petrous part of temporal bone makes the craniotomy around this area challenging. To avoid damaging the interior structures of petrous part of temporal bone, the authors used computed tomography to get the projection of the petrous part of temporal bone on skulls, making the external contours of petrous part clear, thus protecting its interior structure as a reference in craniotomy. The objective of this study was to find out the three-dimensional location of 4 points of petrous part of temporal bone. Parameters of 120 patients (240 observations) between 25 and 65 years who were free of abnormalities and pathological changes in temporal bone were measured on high-resolution spiral multiple slice computed tomographic multiple planar reconstruction images that were parallel to the base plane. The data were analyzed by SPSS, statistical software with the comparison between sides and sexes. The authors found the accurate locations that 4 points of petrous part of temporal bone with mastoidale as the origin. Then the authors connect the 3 vertexes of underside and the petrous apex and lengthen it until intersect with skulls to get the external landmarks. In the end, the authors get the safe range that can be applied to the clinical surgery. PMID- 27557462 TI - Corrugator: Muscle of Empathy and Determination. PMID- 27557466 TI - Simplified Calvarial Reconstruction: Coverage of Bare Skull With GammaGraft Promotes Granulation and Facilitates Skin Grafting. AB - Repair of scalp defects with exposed calvaria remains a difficult clinical problem. Herein, we present a simple alternative method of scalp reconstruction. Coverage of bare skull with GammaGraft (Promethean LifeSciences, Inc, Pittsburgh, PA) promotes the evolution of granulation tissue and permits subsequent skin grafting without need for burring, drilling, or other manipulation of the outer table of the calvaria. A retrospective review of patients undergoing scalp reconstruction utilizing GammaGraft and subsequent skin grafting was performed at our institution. From our cohort, 5 patients treated with GammaGraft and subsequent skin grafting had both immediate and long-term follow-up available. Indications for scalp reconstruction included erosions of prior skin grafts and direct excision of full-thickness scalp and pericranium. Average time to definitive skin grafting was 3 weeks; repeat application of GammaGraft was required in some patients with reapplication to subsequent smaller wounds as healing occurred. Complications were minor and consisted of ongoing wound drainage. Alternative flap reconstruction was not required in any patient due to treatment failures. No major complications, wound infections, or early reoperations occurred in any of the patients; 1 patient to date has required repeat reconstruction due to recurrent disease. Coverage of bare skull with GammaGraft and subsequent skin grafting provides a simple and elegant solution to an often too difficult clinical problem. Confirmed by results in out limited series, the utilization of GammaGraft in calvarial reconstruction represents an alternative method in surgical care of complex scalp defects with exposed bone. PMID- 27557467 TI - Abdominal Retraction Pad Used in Orthognathic Surgery: A Novel Technique for Nasotracheal Tube Stabilization During Le Fort I Osteotomy. AB - Many types of surgical osteotomies of the cranio-facial skeleton relay on adequate surgical field preparation. Placement and stabilization of nasotracheal tube during orthognathic surgery is very important. In most cases, long-lasting surgery includes various surgical maneuvers around patient's skull, which depend on accurate nasotracheal tube stabilization. Usage of adhesive plasters for heavy anesthetic tube connector placement and stability might result in tube instability and local disfigurement of nasal projection and visibility in the nasal and infraorbital areas. We present a novel technique for nasotracheal tube stabilization allowing each surgeon controlling tube position, visual evaluation of nasal projection, and its tip during various surgical movements of maxillary bone, such as extrusion, intrusion, rotation or others, during Le Fort I osteotomy. Despite additional time necessary for preparation of surgical field, attachment of the tube and suturing, presented method allows achieving very satisfactory final outcomes with visible access to key nasal structures important in Le Fort I osteotomy. Presented method could be also used in any other facial surgery procedure. PMID- 27557468 TI - Combination of Sturge-Weber Syndrome and Trigonocephaly. AB - Regarded singly, both Sturge-Weber syndrome and trigonocephaly are rare congenital disorders. The cardinal features of Sturge-Weber syndrome are facial cutaneous capillary malformation (port-wine stain), leptomeningeal angiomatosis, and glaucoma. Premature closure of the metopic suture results in trigonocephaly. However, to the best of our knowledge, the diagnosis of a combination of both Sturge-Weber syndrome and trigonocephaly has not as yet been reported. This brief clinical study thus presents a patient with the unusual findings of a Sturge Weber syndrome and simultaneous trigonocephaly induced by premature metopic synostosis. Thus, the rare combination of a port-wine stain involving the first division of the trigeminal nerve with the diagnosis of a craniosynostosis justifies the indication of a prophylactic magnetic resonance imaging acquisition before craniofacial surgeries, in order to prevent seizures and stroke-like episodes triggered by the surgical intervention. PMID- 27557469 TI - Transoral Fully Robotic Dissection of a Parapharyngeal Hemangioma. AB - Soft tissue robotics found its trigger for success in minimally invasive surgery. The minimization of the surgical damage is more obvious as the surgical alternative is more aggressive. In head and neck surgery, potential sequelae are both functional and cosmetic. Robotic instrumentation might allow for further development of the transoral approach to the deep regions of the face.The authors present an uneventful, fully robotic, transoral surgical excision of a parapharyngeal hemangioma. The authors discuss management alternatives, surgical risks, and safety measures. The medial approach is the natural choice, provided it is safe and technically feasible. Transoral robotic surgery could be a reasonable minimally invasive approach for selected parapharyngeal tumors. PMID- 27557470 TI - Identifying clinically relevant sources of variability: The clopidogrel challenge. AB - High interindividual variability in clinical outcomes following clopidogrel's standard dosing regimen continues to be a challenge even two decades after its approval. CYP2C19 polymorphisms, obesity, older age, diabetes, and drug-drug interactions have been identified as risk factors for adverse events and treatment failure. We conducted a mechanism-based pharmacokinetic/pharmacodynamic analysis, where we integrated knowledge on in vitro enzyme kinetic, physiological, genetic, and demographic information to characterize changes in platelet reactivity from baseline following clopidogrel antiplatelet therapy. When considering the combined impact of these covariates, our analysis results indicate that higher maintenance doses are required for CYP2C19 intermediate metabolizers and poor metabolizers compared to extensive metabolizers and that respective maintenance doses have to be further increased for obese subjects for each of these CYP2C19 phenotypes. In addition, interindividual differences in the fraction absorbed and the CES1 activity were identified as sources of interindividual differences in clopidogrel's active metabolite concentrations and, thus, platelet reactivity. PMID- 27557471 TI - Apoptosis of keratinocytes and serum DNase I activity in patients with cutaneous lupus erythematosus: relationship with clinical and immunoserological parameters. AB - BACKGROUND: Dysregulation of apoptosis has an important role in the induction of autoimmunity. OBJECTIVE: To evaluate the influence of keratinocyte apoptosis and deoxyribonuclease I (DNase I) activity on the clinical and immunoserological parameters of cutaneous lupus erythematosus (CLE). METHODS: We studied 69 CLE patients (39 with discoid LE (DLE), 12 with subacute CLE (SCLE), 12 with acute and 6 with intermittent CLE). Thirty of sixty-nine patients fulfilled criteria for systemic LE (SLE). Apoptotic index (AI) was evaluated immunohistochemically in lesional and non-lesional, photoprotected skin. Serum DNase I activity, antichromatin and anti-ENA antibodies were measured by ELISA. Disease activity was determined by SLEDAI-2K, SLICC/ACR, CLASI and RCLASI. RESULTS: AI in lesions was higher than in non-lesional skin (P < 0.001). There was no difference in AI between CLE and SLE patients. Patients with SCLE had higher lesional AI than patients with DLE (P < 0.05). We found a positive correlation between the lesional AI with CLASI A (P < 0.05) and RCLASI D (P < 0.05). CLE and SLE patients had significantly lower DNase I activity than healthy controls (P < 0.001). Patients with normal DNase I activity and low AI had significantly lower CLASI A than patients with decreased DNase I activity and/or elevated AI (P < 0.05). CONCLUSIONS: Increased keratinocyte apoptosis characterizes lesions of all CLE forms, especially of SCLE. AI correlates with CLE markers of acute and chronic inflammation. Normal level of apoptosis and DNase I activity simultaneously reduce the level of acute inflammation in CLE. Serum DNase I activity and AI might be important biomarkers in the evaluation of CLE patients. PMID- 27557472 TI - Linking in Vitro Lipolysis and Microsomal Metabolism for the Quantitative Prediction of Oral Bioavailability of BCS II Drugs Administered in Lipidic Formulations. AB - Lipidic formulations (LFs) are increasingly utilized for the delivery of drugs that belong to class II of the Biopharmaceutics Classification System (BCS). The current work proposes, for the first time, the combination of in vitro lipolysis and microsomal metabolism studies for the quantitative prediction of human oral bioavailability of BCS II drugs administered in LFs. Marinol and Neoral were selected as model LFs, and their observed oral bioavailabilities (Fobserved) were obtained from published clinical studies in humans. Two separate lipolysis buffers, differing in the level of surfactant concentrations, were used for digestion of the LFs. The predicted fraction absorbed (Fabs) was calculated by measuring the drug concentration in the micellar phase after completion of the lipolysis process. To determine first-pass metabolism (Fg.Fh), drug depletion studies with human microsomes were performed. Clearance values were determined by applying the "in vitro half-life" approach. The estimated Fabs and Fg.Fh values were combined for the calculation of the predicted oral bioavailability (Fpredicted). Results showed that there was a strong correlation between Fobserved and Fpredicted values only when Fabs was calculated using a buffer with surfactant concentrations closer to physiological conditions. The general accuracy of the predicted values suggests that the novel in vitro lipolysis/metabolism approach could quantitatively predict the oral bioavailability of lipophilic drugs administered in LFs. PMID- 27557473 TI - The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q): a validated 6-item questionnaire as a diagnostic aid for empty nose syndrome patients. AB - BACKGROUND: Empty nose syndrome (ENS) is considered an acquired condition that remains difficult to diagnose objectively. Defining specific symptoms that can be reliably associated with this disorder would be essential to identifying possible ENS patients. We sought to validate an ENS-specific, 6-item questionnaire as an adjunct to the standard Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire to discriminate patients suspected of having ENS. METHODS: The Empty Nose Syndrome 6 item Questionnaire (ENS6Q) paired 6 common ENS symptoms (nasal suffocation, nasal burning, nasal openness, crusting, dryness, and impaired air sensation through nasal cavities) with testing on 75 patients divided in 3 patient cohorts: ENS; chronic rhinosinusitis without polyposis; and healthy controls. Participants answered 2 rounds of both the SNOT-22 questionnaire and ENS6Q within 48 hours of each other. No changes in treatments occurred in the test interval between questionnaires. Internal consistency, test-retest reliability, validity, and area under the curve were assessed to differentiate between patient cohorts using the 2 instruments. RESULTS: We found high internal consistency for ENS6Q and SNOT-22 questionnaire at 0.93 (95% CI, 0.90-0.95) and 0.94 (95% CI, 0.94-0.96), respectively. The test-retest reliability between timepoints for ENS6Q testing was 0.969. The ENS6Q statistically significantly discriminated between ENS and control patients and between ENS and chronic rhinosinusitis without polyposis (CRSsNP) patients, without significant differences between CRSsNP and controls. The area-under-the-curve (AUC) threshold score comparison further supported the ability of the ENS6Q to differentiate ENS from CRSsNP patients. CONCLUSION: The ENS6Q is the first validated, specific, adjunct questionnaire to the SNOT-22 to more reliably identify patients suspected of developing ENS. PMID- 27557474 TI - Unusual Closed Loop Stimulator Responsive Pacing in a Patient with Paroxysmal Atrial Fibrillation. PMID- 27557475 TI - Polytetrafluoroethylene-jacketed stirrer modified with graphene oxide and polydopamine for the efficient extraction of polycyclic aromatic hydrocarbons. AB - Steel stirrers jacketed with polytetrafluoroethylene can be regarded as an ideal substrate for stirrer bar sorptive extraction. However, it is still a great challenge to immobilize graphene onto a polytetrafluoroethylene stirrer due to the high chemical resistance of the surface of a polytetrafluoroethylene stirrer. We describe here a method to modify the surface of polytetrafluoroethylene stirrers with graphene. In this work, graphene was used as the sorbent due to its excellent adsorption capability for aromatic compounds, such as polycyclic aromatic compounds. Graphene was successfully immobilized onto polytetrafluoroethylene-stirrer by a bio-inspired polydopamine functionalization method. The graphene-modified polytetrafluoroethylene-stirrer shows good stability and tolerance to stirring, ultrasonication, strong acidic and basic solutions, and to organic solvents. The multilayer coating was characterized by scanning electronic microscopy and Fourier transform infrared spectroscopy. After the optimization of some experimental conditions, the graphene-modified polytetrafluoroethylene stirrer was used for the stirrer bar sorptive extraction of polycyclic aromatic hydrocarbons, in which the binding between the polycyclic aromatic hydrocarbons and the graphene layer was mainly based on pi-pi stacking and hydrophobic interactions. The graphene-modified polytetrafluoroethylene stirrer-based stirrer bar sorptive extraction and high-performance liquid chromatography method was developed for the determination of polycyclic aromatic hydrocarbons with great extraction efficiency, with enrichment factors from 18 to 62. The method has low limits of detection of 1-5 pg/mL, wide linear range (5-100 and 10-200 pg/mL), good linearity (R >= 0.9957) and good reproducibility (RSD <= 6.45%). The proposed method has been applied to determine polycyclic aromatic hydrocarbons in real dust samples. Good recoveries were obtained, ranging from 88.53 to 109.43%. PMID- 27557477 TI - Effect of proinflammatory cytokine IL-6 on efflux transport of rebamipide in Caco 2 cells. AB - 1. Effect of IL-6, a pro-inflammatory cytokine, on efflux transport of rebamipide, an antiulcer drug, was investigated in Caco-2 cells. 2. Rebamipide had a greater basal-to-apical than apical-to-basal transport rate. Efflux transport of rebamipide was inhibited by cyclosporine A, a P-gp inhibitor, and probenecid, which is a general MRP inhibitor, but not by Ko143, a BCRP inhibitor. 3. By the addition of IL-6, mannitol transport was slightly increased in a concentration-dependent manner in both directions of absorption and efflux. The addition of IL-6 did not change efflux transport of rebamipide even though efflux transport of digoxin, a typical substrate of P-gp, was significantly decreased by the addition of IL-6, indicating decrease of the function of P-gp. 4. Therefore, it was suggested that increase of MRP(s)-mediated transport compensates for the decrease of P-gp mediated transport of rebamipide. These findings suggested that rebamipide absorption is unlikely to be changed in IBD patients. PMID- 27557476 TI - National and International Guidelines for Patient Blood Management in Obstetrics: A Qualitative Review. AB - In developed countries, rates of postpartum hemorrhage (PPH) requiring transfusion have been increasing. As a result, anesthesiologists are being increasingly called upon to assist with the management of patients with severe PPH. First responders, including anesthesiologists, may adopt Patient Blood Management (PBM) recommendations of national societies or other agencies. However, it is unclear whether national and international obstetric societies' PPH guidelines account for contemporary PBM practices. We performed a qualitative review of PBM recommendations published by the following national obstetric societies and international groups: the American College of Obstetricians and Gynecologists; The Royal College of Obstetricians and Gynecologists, United Kingdom; The Royal Australian and New Zealand College of Obstetricians and Gynecologists; The Society of Obstetricians and Gynecologists of Canada; an interdisciplinary group of experts from Austria, Germany, and Switzerland, an international multidisciplinary consensus group, and the French College of Gynaecologists and Obstetricians. We also reviewed a PPH bundle, published by The National Partnership for Maternal Safety. On the basis of our review, we identified important differences in national and international societies' recommendations for transfusion and PBM. In the light of PBM advances in the nonobstetric setting, obstetric societies should determine the applicability of these recommendations in the obstetric setting. Partnerships among medical, obstetric, and anesthetic societies may also help standardize transfusion and PBM guidelines in obstetrics. PMID- 27557479 TI - Analysis of the articular cartilage T1rho and T2 relaxation times changes after ACL reconstruction in injured and contralateral knees and relationships with bone shape. AB - The objectives of this study were twofold: (1) to evaluate the longitudinal change in cartilage T1rho and T2 6- and 12-months after ACL reconstruction (ACLR) in both reconstructed and intact contralateral knees with the aim of validating the role of the contralateral knee as an internal control in longitudinal studies; (2) to explore relationships between bone shape at the time of injury and the progression of T1rho and T2 over 12-months after ACLR. T1rho and T2 cartilage relaxation times and 3D MRI-based statistical shape modeling (SSM) of tibia and femur were computed for both knees of forty ACL-injured patients and 15 healthy controls. ACL subjects were scanned 8.4 +/- 6.4 weeks after injury (2.4 +/- 3.7 weeks prior to ACLR), 6- and 12-months after ACLR. Longitudinal changes in T1rho and T2 values were assessed using linear mixed model, and partial correlation coefficients were calculated between bone shape and longitudinal changes in T1rho and T2 values. Significant longitudinal increases in T1rho and T2 values were observed in reconstructed and contralateral knees 6-months after ACLR. Tibial bone shape features, associated with the medial plateau height and width, were observed to be correlated with cartilage T1rho and T2 progression in reconstructed knees. Our results suggest that caution should be used in considering contralateral knee as internal controls in longitudinal ACL studies and 3D MRI-based-SSM might serve as an imaging biomarker for the early stratification of patients at risk for developing post-traumatic accelerated cartilage degeneration and potentially osteoarthritis after ACL tear. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:707-717, 2017. PMID- 27557478 TI - A comprehensive draft genome sequence for lupin (Lupinus angustifolius), an emerging health food: insights into plant-microbe interactions and legume evolution. AB - Lupins are important grain legume crops that form a critical part of sustainable farming systems, reducing fertilizer use and providing disease breaks. It has a basal phylogenetic position relative to other crop and model legumes and a high speciation rate. Narrow-leafed lupin (NLL; Lupinus angustifolius L.) is gaining popularity as a health food, which is high in protein and dietary fibre but low in starch and gluten-free. We report the draft genome assembly (609 Mb) of NLL cultivar Tanjil, which has captured >98% of the gene content, sequences of additional lines and a dense genetic map. Lupins are unique among legumes and differ from most other land plants in that they do not form mycorrhizal associations. Remarkably, we find that NLL has lost all mycorrhiza-specific genes, but has retained genes commonly required for mycorrhization and nodulation. In addition, the genome also provided candidate genes for key disease resistance and domestication traits. We also find evidence of a whole-genome triplication at around 25 million years ago in the genistoid lineage leading to Lupinus. Our results will support detailed studies of legume evolution and accelerate lupin breeding programmes. PMID- 27557480 TI - Bilateral vocal fold paralysis and dysphagia secondary to diffuse idiopathic skeletal hyperostosis. AB - BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is an idiopathic spinal disease common in the elderly and characterized by flowing ossification and osteophyte formation along the spinal column. Cervical hyperostosis is capable of producing dysphagia, stridor, and airway obstruction; however, there are no extant reports of true paralysis of bilateral vocal folds in patients fulfilling the criteria for DISH. METHODS AND RESULTS: We report a case of a 61 year-old man presenting with dysphagia and dyspnea. Flexible laryngoscopy revealed bilateral true vocal fold paralysis. Cervical radiograph showed flowing ossification of the anterior longitudinal ligament with preservation of intervertebral disc height. Tracheotomy and cervical osteophytectomy were performed, after which the patient showed improved swallowing and speaking ability and was decannulated without complication. CONCLUSION: In the case presented, cervical osteophytectomy dramatically reversed bilateral vocal fold paralysis and dysphagia secondary to hyperostosis, thus negating the need for prolonged tracheostomy and feeding tube dependence. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: E1-E3, 2017. PMID- 27557481 TI - Decrease in somatostatin-positive cell density in the amygdala of females with major depression. AB - BACKGROUND: Somatostatin (SST) is a neuropeptide expressed in a subtype of gamma aminobutyric acid (GABA) interneurons that target the dendrites of pyramidal neurons. We previously reported reduced levels of SST gene and protein expression in the postmortem amygdala of subjects with major depressive disorder (MDD). This reduction was specific to female subjects with MDD. METHODS: Here, we used in situ hybridization to examine the regional and cellular patterns of reductions in SST expression in a cohort of female MDD subjects with known SST deficits in the amygdala (N = 10/group). RESULTS: We report a significant reduction in the density of SST-labeled neurons in the lateral, basolateral, and basomedial nuclei of the amygdala of MDD subjects compared to controls. SST mRNA levels per neuron did not differ between MDD and control subjects in the lateral or basolateral nuclei, but were lower in the basomedial nucleus. There was no difference in cross-sectional density of total cells. CONCLUSIONS: In summary, we report an MDD related reduction in the density of detectable SST-positive neurons across several nuclei in the amygdala, with a reduction in SST mRNA per cell restricted to the basomedial nucleus. In the absence of changes in total cell density, these results suggest the possibility of a change in SST cell phenotype rather than cell death in the amygdala of female MDD subjects. PMID- 27557482 TI - Determination of dihydroartemisinic acid in Artemisia annua L. by gas chromatography with flame ionization detection. AB - Dihydroartemisinic acid (DHAA) is the direct precursor to artemisinin, an effective anti-malaria compound from Artemisia annua L. (A. annua), and it can be transformed to artemisinin without the catalysis of enzyme. A rapid and sensitive analysis of DHAA in A. annua is needed to screen excellent plant resources aimed to improve artemisinin production. In order to develop a rapid and sensitive determination method for DHAA in plant, the extraction and analysis conditions were extensively investigated in the present work. As a result, extraction of powdered A. annua leaves at 55 degrees C for 50 min with chloroform resulted in the highest yield of DHAA, with a recovery of >98%. The precision of this gas chromatographic procedure ranged from 1.22 to 2.94% for intra-day and from 1.69 to 4.31% for inter-day, respectively. The accuracy was 99.55-103.02% for intra day and 98.86-99.98% for inter-day, respectively. The measured LOQ and LOD values of the proposed method reached 5.00 and 2.00 MUg/mL, respectively. Validation indicated the method was robust, quick, sensitive and adequate for DHAA analysis. PMID- 27557483 TI - Reconstructive transoral laser microsurgery for posterior glottic web with stenosis. AB - OBJECTIVES/HYPOTHESIS: To demonstrate that reconstructive transoral laser microsurgical (R-TLM) techniques can be used for the treatment of symptomatic laryngeal posterior glottic web-based stenosis (PGWS) in a large cohort of patients utilizing a postcricoid mucosal advancement flap (PCMAF). STUDY DESIGN: Retrospective cohort review. METHODS: A consecutive series of patients with PGWS who underwent R-TLM using a PCMAF were reviewed for outcomes. After laser excision of the PGWS scar and mobilization of fixed cricoarytenoid joints, a PCMAF was raised using microinstruments and a scanning free-beam CO2 laser. The flap was advanced and attached over the scar bed using a technique with multiple novel features that make it easy to adopt. RESULTS: Fifty-two patients were treated. Of the cases, 42.3% had a tracheostomy at presentation with grade II to IV PGWS, and 46% of cases had grade III to IV PGWS. In all cases, R-TLM was the only treatment approach. No open reconstructions were performed. No airway stents were used. Patients without tracheostomy, regardless of the grade of stenosis, did not require a tracheostomy to undergo this operation. All tracheostomy patients were successfully decannulated. All patients without a tracheostomy had significant improvement of their respiratory symptoms on the Dyspnea Index (mean Delta = 14.75, P value <.01). CONCLUSIONS: RTLM using the PCMAF is a feasible, safe, and effective alternative to open approaches for airway reconstruction for PGWS. This novel transoral technique includes a much simpler endoscopic suturing alternative to knot tying among other new features. It is reproducible and reliable for laryngologists familiar with laryngeal microsurgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:685-690, 2017. PMID- 27557484 TI - Participation and adherence to cardiac rehabilitation programs. A systematic review. AB - Acute myocardial infarction (AMI) is an important health problem. Cardiac rehabilitation (CR) programs following AMI have shown to be effective in reducing mortality. We aim to systematically review the existing literature that analyzes the factors that affect participation and adherence to cardiac rehabilitation programs. We reviewed Medline, EMBASE and Cochrane databases from 01/01/2004 to June 2016 using predefined inclusion and exclusion criteria. We classified the results into factors affecting participation and factors influencing adherence to CR programs. We included 29 studies, and there was a general agreement in those factors predicting participation and adherence to CR programs. These factors can be classified into person-related factors and aspects related to CR programs. Older participants, women, patients with comorbidities, unemployed and uncoupled persons, less educated people and those with lower income had a lower participation. A similar pattern was observed for CR adherence. Also, those potential participants who live farther from CR facilities, do not have transportation, or do not drive, attended less to CR programs. These factors were very similar when analyzing adherence to CR programs. These aspects were similar in Europe and the USA. These results clearly show that participation in CR programs follows a determined pattern that is very homogeneous in different settings. Health professionals should also be aware of patients reluctant to participate in CR programs and adapt their messages and redesign CR programs, to promote participation and adherence. PMID- 27557485 TI - Stent design parameters and crimpability. PMID- 27557486 TI - Minimally invasive cardiac surgery: A systematic review and meta-analysis. AB - BACKGROUND: Minimally invasive (MI) cardiac surgery was introduced to reduce problems associated with a full sternotomy. This meta-analysis aimed to investigate the effects of minimally invasive cardiac surgery on a range of clinical outcomes. METHODS: To identify potential studies (randomised/prospective clinical trials) systematic searches were carried out. The search strategy included the concepts of "minimally invasive" OR "MIDCAB" AND "coronary artery bypass grafting" OR "cardiac surgery". This was followed by a meta-analysis investigating cross-clamp time, cardiopulmonary bypass (CPB) time, operation time, ventilation time, intensive care unit (ICU) stay, hospital stay, incidence of myocardial infarction and of stroke/neurologic complications. RESULTS: Eight studies (9 intervention groups), totalling 596 participants were analysed. MI cardiac surgery was associated with a shorter ICU stay mean difference (MD) 0.7days (95% confidence interval (CI) -1.23 to -0.18, p=0.009) and longer cross clamp MD 6.7min (95% CI 1.24 to 12.17, p=0.02), CPB MD 26.68min (95% CI 10.31 to 43.05, p=0.001), and operation times MD 55.03min (95% CI 22.76 to 87.31, p=0.0008). However no differences were found in the ventilation time MD -3.94h (95% CI -8.09 to 0.21, p=0.06), length of hospital stay MD -1.14days (95% CI 3.11 to 0.83, p=0.26) and in the incidence of myocardial infarction odds ratio (OR) 1.97 (95% CI 0.49 to 7.9, p=0.34) or stroke/neurologic complications OR 0.67 (95% CI 0.11 to 4.05, p=0.66). CONCLUSIONS: Minimally invasive cardiac surgery is as safe as conventional surgery and could reduce costs due to a shorter period spent in ICU. PMID- 27557487 TI - Could personalized bio-3D printing rescue the cardiovascular system? PMID- 27557488 TI - Atrial Tachycardia Originating in the Vicinity of the Noncoronary Sinus of Valsalva: Report of a Series Including the First Case of Ablation-Related Complete Atrioventricular Block. AB - BACKGROUND: A few series of focal atrial tachycardia (AT) originating from the noncoronary sinus of Valsalva (NCSV) have been reported in the literature during the last decade. METHODS AND RESULTS: Of 147 patients with AT referred for radiofrequency ablation (RFA), we identified nine (6%) originating in the vicinity of the NCSV. Clinical AT was induced during electrophysiological study in all patients without (n = 6) and with (n = 3) isoproterenol infusion. Mean cycle length of the induced tachycardia was 399 +/- 85 ms. Mapping of the right atrium and of the left atrium (LA) was initially performed in all nine patients and in four patients, respectively. Earliest tachycardia activation occurred at the His bundle area in all cases. Earliest activations in the LA were at the low paraseptal regions. In two patients with antegrade dual atrioventricular (AV) node physiology that rendered difficult accurate distinction between atrial and ventricular activation, slow pathway ablation was necessary. A retrograde aortic approach was used for mapping the aortic cusps. The earliest local atrial activation in the NCSV preceded the atrial activation in the His area in all patients by 27 +/- 8 ms. RFA was performed in all nine patients and was acutely successful in eight. Two patients required radiofrequency (RF) energy outputs of 50 W in order to terminate the arrhythmia. In one patient, successful AT ablation was associated with complete AV block requiring implantation of permanent pacemaker. CONCLUSIONS: Focal AT can be successfully mapped and ablated in the NCSV. Higher than usual RF energy levels are sometimes required. Complete AV block is a possible complication. PMID- 27557489 TI - A retrospective evaluation of contrast-induced kidney injury in dogs (2006-2012). AB - OBJECTIVE: To evaluate a population of dogs for evidence of contrast-induced nephropathy (CIN). DESIGN: A retrospective case review between 2006 and 2012. SETTING: A university teaching hospital. ANIMALS: A total of 1,217 client-owned dogs that were administered intravenous iodinated contrast agents were reviewed for evidence of CIN. Inclusion required a measured serum creatinine within 1 week prior as well as within 1 week following administration of contrast. Eighty-six dogs with 92 contrast administrations qualified for inclusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CIN was defined as an increase in >44.2 MUmol/L (0.5 mg/dL) from baseline creatinine concentration within 1 week following administration of an intravenous iodinated contrast agent. A total of 7.6% of contrast administrations (7/92) fulfilled the definition of CIN. The creatinine postcontrast administration as well as the change in creatinine concentration was significantly higher in the CIN group than in the non-CIN group (median postcreatinine 150 MUmol/L [1.7 mg/dL] versus 70.7 MUmol/L [0.8 mg/dL], median change in creatinine 53 MUmol/L [0.6 mg/dL] versus 0 MUmol/L). Patient signalment, initial creatinine, number of total contrast administrations, dose of contrast received, duration of anesthesia, IV fluid administration, administration of nephrotoxic agents, and use or vasopressor therapy were not significantly different between groups. CONCLUSIONS: The temporal association between contrast administration and renal injury in these cases highlights the potential for CIN in dogs. Due to the retrospective nature of this study, a causal association between contrast administration and renal injury cannot be determined. A prospective study is needed to further evaluate CIN in dogs. PMID- 27557490 TI - Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study. AB - Cancer stem cells (CSCs) are thought as the source of tumor maintaining and many CSCs markers have been identified. Regarding the heterogeneity in gastric cancer (GC), TNM stage is not enough to accurately predict the prognosis. The aim of this study was to investigate the clinical significance of CSCs markers (Lgr5, Oct4, CD133, EpCAM, CD54 and Sox2) and establish a new model based on these markers to accurately predict prognosis of GC. We retrospectively enrolled 377 GC tissues from January 2006 to October 2012 to perform immunohistochemistry (IHC), and 93 pairs of GC tissues and corresponding adjacent normal gastric tissues to perform quantitative PCR (qPCR) from December 2011 to October 2012. The clinicopathological and follow-up characteristics were collected. In IHC, Oct4, CD133 and EpCAM were independently related to tumor progression, while Sox2 were associated with well or moderate differentiation (all p<0.05). Cox regression showed that Oct4-EpCAM was an independently prognostic factor, indicating that double low expression of Oct4-EpCAM group had significantly better prognosis than control group (p=0.035). Regarding qPCR, CD133 was an independent prognostic factor, showing that the prognosis of patients with CD133 high expression was significantly worse than that of patients with CD133 low expression (p<0.001). The prognostic prediction accuracy of nomogram based on Oct4-EpCAM expression in IHC was significantly better than TNM stage alone (p=0.003). Low expressions of Oct4-EpCAM in IHC and CD133 in qPCR were favorable prognostic factors in GC. The nomogram based on Oct4-EpCAM was valuable in prognostic prediction of GC patients. PMID- 27557491 TI - Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells. AB - Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway. PMID- 27557492 TI - Foxp3 enhances HIF-1alpha target gene expression in human bladder cancer through decreasing its ubiquitin-proteasomal degradation. AB - Hypoxia-inducible factor-1alpha (HIF-1alpha) can control a transcriptional factor forkhead box P3 (Foxp3) protein expression in T lymphocyte differentiation through proteasome-mediated degradation. In this study, we unveil a reverse regulatory mechanism contributing to bladder cancer progression; Foxp3 expression attenuates HIF-1alpha degradation. We first demonstrated that Foxp3 expression positively correlates with the metastatic potential in T24 cells and can increase the expression of HIF-1alpha-target genes, such as vascular endothelial growth factor (VEGF) and glucose transporter (GLUT). Foxp3 protein can bind with HIF 1alpha, particularly under hypoxia. In vivo ubiquination assay demonstrated that Foxp3 can decrease HIF-1alpha degradation in a dose-dependent manner. Knocking down of Foxp3 expression blocks in vivo tumor growth in mice and prolongs mice's survival, which is associated with von Willebrand factor expression. Thirty-three of 145 (22.8 %) bladder tumors exhibit Foxp3 expression. Foxp3 expression is an independent predictor for disease progression in superficial bladder cancer patients (p = 0.032), associated with less number of intratumoral CD8+ lymphocyte. The metaanalysis from 2 published datasets showed Foxp3 expression is positively associated with GLUT-4,-9, and VEGF-A, B-, D expression. This reverse post-translational regulation of HIF-1alpha protein by Foxp3 provides a new potential target for developing new therapeutic strategy for bladder cancer. PMID- 27557493 TI - Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1 pathway. AB - There is an urgent need for new therapeutic strategies for patients with glioblastoma multiforme (GBM). Previous studies have shown that berberine (BBR), a natural plant alkaloid, has potent anti-tumor activity. However, the mechanisms leading to cancer cell death have not been clearly elucidated. In this study, we show that BBR has profound effects on the metabolic state of GBM cells, leading to high autophagy flux and impaired glycolytic capacity. Functionally, these alterations reduce the invasive properties, proliferative potential and induce apoptotic cell death. The molecular alterations preceding these changes are characterized by inhibition of the AMPK/mTOR/ULK1 pathway. Finally, we demonstrate that BBR significantly reduces tumor growth in vivo, demonstrating the potential clinical benefits for autophagy modulating plant alkaloids in cancer therapy. PMID- 27557494 TI - Pesticide exposure and risk of bladder cancer: A meta-analysis. AB - OBJECTIVE: We conducted a meta-analysis to quantitatively evaluate the correlation between pesticide exposure and the risk of bladder cancer by summarizing the results of published case-control and cohort studies. METHODS: A systematic literature search of articles update to February 2015 was conducted via Pubmed, Web of Science, Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI) databases, and the references of the retrieved articles. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs for the highest versus the lowest exposure of pesticide. RESULTS: The pooled OR estimates indicated that pesticide exposure was associated with an increased risk of bladder cancer (OR=1.649, 95% CI 1.223-2.223). In subgroup analysis, we detected pesticide exposure demonstrated as a significant risk factor on bladder cancer in America (OR=1.741, 95% CI 1.270-2.388). Similar results were discovered in both case-control group and cohort group (OR=2.075, 95% CI 1.183-3.638, OR=1.146, 95% CI 1.074-1.223, respectively). No evidence of publication bias was found by Begg's or Egger's test (P = 0.210, P = 0.358, respectively). CONCLUSION: In conclusion, our meta-analysis indicated that pesticide exposure was associated with an increased risk of bladder cancer. Further researches should be conducted to confirm the findings in our study and better clarify the potential biological mechanisms. PMID- 27557495 TI - Therapeutic relevance of the protein phosphatase 2A in cancer. AB - Chromosomal Instability (CIN) is regarded as a unifying feature of heterogeneous tumor populations, driving intratumoral heterogeneity. Polo-Like Kinase 1 (PLK1), a serine-threonine kinase that is often overexpressed across multiple tumor types, is one of the key regulators of CIN and is considered as a potential therapeutic target. However, targeting PLK1 has remained a challenge due to the off-target effects caused by the inhibition of other members of the polo-like family. Here we use synthetic dosage lethality (SDL), where the overexpression of PLK1 is lethal only when another, normally non-lethal, mutation or deletion is present. Rather than directly inhibiting PLK1, we found that inhibition of PP2A causes selective lethality to PLK1-overexpressing breast, pancreatic, ovarian, glioblastoma, and prostate cancer cells. As PP2A is widely regarded as a tumor suppressor, we resorted to gene expression datasets from cancer patients to functionally dissect its therapeutic relevance. We identified two major classes of PP2A subunits that negatively correlated with each other. Interestingly, most mitotic regulators, including PLK1, exhibited SDL interactions with only one class of PP2A subunits (PPP2R1A, PPP2R2D, PPP2R3B, PPP2R5B and PPP2R5D). Validation studies and other functional cell-based assays showed that inhibition of PPP2R5D affects both levels of phospho-Rb as well as sister chromatid cohesion in PLK1-overexpressing cells. Finally, analysis of clinical data revealed that patients with high expression of mitotic regulators and low expression of Class I subunits of PP2A improved survival. Overall, these observations point to a context-dependent role of PP2A that warrants further exploration for therapeutic benefits. PMID- 27557496 TI - Dual targeting of androgen receptor and mTORC1 by salinomycin in prostate cancer. AB - Androgen receptor (AR) and PI3K/AKT/mTORC1 are major survival signals that drive prostate cancer to a lethal disease. Reciprocal activation of these oncogenic pathways from negative cross talks contributes to low/limited success of pathway selective inhibitors in curbing prostate cancer progression. We report that the antibiotic salinomycin, a cancer stem cell blocker, is a dual-acting AR and mTORC1 inhibitor, inhibiting PTEN-deficient castration-sensitive and castration resistant prostate cancer in culture and xenograft tumors. AR expression, its transcriptional activity, and androgen biosynthesis regulating enzymes CYP17A1, HSD3beta1 were reduced by sub-micro molar salinomycin. Estrogen receptor-alpha expression was unchanged. Loss of phosphorylated AR at serine-81, which is an index for nuclear AR activity, preceded total AR reduction. Rapamycin enhanced the AR protein level without altering phosphoAR-Ser81 and CYP17A1. Inactivation of mTORC1, evident from reduced phosphorylation of mTOR and downstream effectors, as well as AMPK activation led to robust autophagy induction. Apoptosis increased modestly, albeit significantly, by sub-micro molar salinomycin. Enhanced stimulatory TSC2 phosphorylation at Ser-1387 by AMPK, and reduced inhibitory TSC2 phosphorylation at Ser-939/Thr-1462 catalyzed by AKT augmented TSC2/TSC1 activity, which led to mTORC1 inhibition. AMPK-mediated raptor phosphorylation further reduced mTOR's kinase function and mTORC1 activity. Our novel finding on dual inhibition of AR and mTORC1 suggests that salinomycin is potentially active as monotherapy against advanced prostate cancer. PMID- 27557497 TI - The emerging insights into catalytic or non-catalytic roles of TET proteins in tumors and neural development. AB - The Ten-eleven translocation (TET) proteins have been recently identified as critical regulators in epigenetic modification, especially in the methylation of cytosine in DNA. TET-mediated DNA oxidation plays prominent roles in a wide variety of physiological and pathological processes, especially in tumor and neural development. TET proteins execute stepwise enzymatic conversion of 5 methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to the more proverbial enzymatic role of TET proteins, TET proteins also possess non-enzymatic activity, through interacting with some epigenetic modifiers. In this review article, we focus on TET proteins dual activities (catalytic or non-catalytic) in tumor and neural development. Hence, the clarification of TET proteins dual activities will contribute to our further understanding of neural development and may open the possibility of new therapeutic avenues to human tumors. PMID- 27557498 TI - Gene expression signature based screening identifies ribonucleotide reductase as a candidate therapeutic target in Ewing sarcoma. AB - There is a critical need in cancer therapeutics to identify targeted therapies that will improve outcomes and decrease toxicities compared to conventional, cytotoxic chemotherapy. Ewing sarcoma is a highly aggressive bone and soft tissue cancer that is caused by the EWS-FLI1 fusion protein. Although EWS-FLI1 is specific for cancer cells, and required for tumorigenesis, directly targeting this transcription factor has proven challenging. Consequently, targeting unique dependencies or key downstream mediators of EWS-FLI1 represent important alternative strategies. We used gene expression data derived from a genetically defined model of Ewing sarcoma to interrogate the Connectivity Map and identify a class of drugs, iron chelators, that downregulate a significant number of EWS FLI1 target genes. We then identified ribonucleotide reductase M2 (RRM2), the iron-dependent subunit of ribonucleotide reductase (RNR), as one mediator of iron chelator toxicity in Ewing sarcoma cells. Inhibition of RNR in Ewing sarcoma cells caused apoptosis in vitro and attenuated tumor growth in an in vivo, xenograft model. Additionally, we discovered that the sensitivity of Ewing sarcoma cells to inhibition or suppression of RNR is mediated, in part, by high levels of SLFN11, a protein that sensitizes cells to DNA damage. This work demonstrates a unique dependency of Ewing sarcoma cells on RNR and supports further investigation of RNR inhibitors, which are currently used in clinical practice, as a novel approach for treating Ewing sarcoma. PMID- 27557499 TI - Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme Regulated eIF2alpha kinase in cortical neurons. AB - The activation of N-Methyl D-Aspartate Receptor (NMDAR) by glutamate is crucial in the nervous system function, particularly in memory and learning. NMDAR is composed by two GluN1 and two GluN2 subunits. GluN2B has been reported to participate in the prevalent NMDAR subtype at synapses, the GluN1/2A/2B. Here we studied the regulation of GluN2B expression in cortical neurons finding that glutamate up-regulates GluN2B translation through the action of nitric oxide (NO), which induces the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2alpha). It is a process mediated by the NO-heme-regulated eIF2alpha kinase (HRI), as the effect was avoided when a specific HRI inhibitor or a HRI small interfering RNA (siHRI) were used. We found that the expressed GluN2B co-localizes with PSD-95 at the postsynaptic ending, which strengthen the physiological relevance of the proposed mechanism. Moreover the receptors bearing GluN2B subunits upon NO stimulation are functional as high Ca2+ entry was measured and increases the co-localization between GluN2B and GluN1 subunits. In addition, the injection of the specific HRI inhibitor in mice produces a decrease in memory retrieval as tested by the Novel Object Recognition performance. Summarizing our data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons. PMID- 27557500 TI - Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis. AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by systemic inflammation and multiple organ failures. Dysregulation of T cells plays a critical role in SLE pathogenesis. Our previous study indicates that JKAP (also named DUSP22) inhibits T-cell activation and that JKAP knockout mice develop spontaneous autoimmunity; therefore, we investigated whether JKAP downregulation is involved in SLE patients. JKAP protein levels in purified T cells were examined by immunoblotting using blood samples from 43 SLE patients and 32 healthy controls. SLE patients showed significantly decreased JKAP protein levels in peripheral blood T cells compared to healthy controls. JKAP protein levels in peripheral blood T cells were inversely correlated with SLE disease activity index (SLEDAI) and anti-dsDNA antibody levels. JKAP downregulation in T cells was highly correlated with daily urinary protein amounts and with poor renal outcome in lupus nephritis patients. Notably, the diagnostic power of JKAP downregulation in T cells for active lupus nephritis was higher than those of serum anti-dsDNA antibody, C3, and C4 levels. Moreover, T cell-specific transgenic mice expressing a dominant-negative JKAP mutant developed spontaneous autoimmune nephritis. Furthermore, JKAP-deficient T cells overproduced complement components, soluble ICAM-1, and soluble VCAM-1 in the kidney; these cytokines have been reported to be involved in lupus nephritis. Taken together, JKAP downregulation in T cells is a novel diagnostic and prognostic biomarker for SLE nephritis. PMID- 27557501 TI - Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response. AB - There is an urgent need for new tools for the rapid diagnosis of tuberculosis disease. We evaluated the potentials of 74 host markers as biomarkers for the immunological diagnosis of tuberculosis and monitoring of treatment response. Fifty-five individuals that presented with signs and symptoms requiring investigation for tuberculosis disease were prospectively recruited prior to clinical diagnosis, at a health centre in Cape Town, South Africa. Patients were later classified as having tuberculosis disease or other respiratory diseases (ORD) using a combination of clinical, radiological and laboratory findings. Out of 74 host markers that were evaluated in plasma samples from study participants using a multiplex platform, 18 showed potential as tuberculosis diagnostic candidates with the most promising being NCAM, CRP, SAP, IP-10, ferritin, TPA, I 309, and MIG, which diagnosed tuberculosis disease individually, with area under the ROC curve >=0.80. Six-marker biosignatures containing NCAM diagnosed tuberculosis disease with a sensitivity of 100% (95%CI, 86.3-100%) and specificity of 89.3% (95%CI, 67.6-97.3%) irrespective of HIV status, and 100% accuracy in the absence of HIV infection. Furthermore, the concentrations of 11 of these proteins changed with treatment, thereby indicating that they may be useful in monitoring of the response to tuberculosis treatment. Our findings have potential to be translated into a point-of-care screening test for tuberculosis, after future validation studies. PMID- 27557502 TI - The gasdermin-D pore: Executor of pyroptotic cell death. PMID- 27557503 TI - Protective effects of Huangqin Decoction against ulcerative colitis and associated cancer in mice. AB - Individuals with ulcerative colitis (UC) are at a high risk for developing colorectal cancer (CRC). Huangqin Decoction (HQD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat gastrointestinal symptoms. However, experimental evidence for supporting the clinical practice is lacking. This study used modern biomedical approaches to investigate the protective/preventive effects of HQD in dextran sulfate sodium (DSS)-induced acute/chronic UC and azoxymethane (AOM)/DSS-induced CRC in mice. HQDs were prepared in 4 different ways: HQD-1 and HQD-2 were prepared in boiling water, whereas HQD-3 and HQD-4 were prepared in heated ethanol (70%). For HQD-1 and HQD-3, the 4 constituent herbs were processed together, whereas for HQD-2 and HQD4, these herbs were processed individually and then combined. The mice were administered 9.1 g/kg HQD via oral gavage daily. HQD-1 significantly inhibited DSS-induced acute UC, whereas HQD-3 and HQD-4 exhibited mild ameliorative effects; but HQD-2 had no protective effect and resulted in a higher mortality rate. This higher mortality rate may be due to the greater abundance of baicalein and wogonin in HQD-2 than HQD-1. Furthermore, HQD-1 protected against DSS-induced chronic UC and significantly inhibited AOM/DSS-induced CRC in mice. HQD-1 also inhibited the production of inflammatory cytokines and increased antioxidant capacity both in chronic DSS and AOM/DSS treated mice. Overall, HQD-1 inhibits the development of acute/chronic colitis and prevents colitis-associated CRC, possibly by inhibiting inflammation and preventing oxidative stress induced cellular damage. PMID- 27557504 TI - A novel inflammation-based prognostic score for patients with esophageal squamous cell carcinoma: the c-reactive protein/prognostic nutritional index ratio. AB - BACKGROUND: Inflammation plays a critical role in cancer prognosis. In the current study, we proposed a novel inflammation-based prognostic score, named c reactive protein/prognostic nutritional index ratio (CRP/PNI ratio), for predicting the prognosis for patients with resectable esophageal squamous cell carcinoma (ESCC). RESULTS: The optimal cut-off value was 0.10 for CRP/PNI ratio according to the ROC curve. Patients with CRP/PNI ratio <=0.10 had a significantly better 5-year CSS compared to CRP/PNI ratio >0.10 (44.5% vs. 15.7%, P<0.001). On multivariate analyses, we revealed that CRP/PNI ratio was a significant predictive factor of CSS (P=0.009). A nomogram could be more accuracy for CSS. The Harrell's c-index for CSS prediction was 0.688. MATERIALS AND METHODS: A total of 308 patients with resectable ESCC were enrolled in this retrospective study. The optimal cuf-off value for CRP/PNI ratio was calculated by a receiver operating characteristic (ROC) curve. Kaplan-Meier methods were used to analyse the cancer-specific survival (CSS). Univariate and multivariate analyses were evaluated for CSS. A nomogram was also established to predict the prognosis for CSS. CONCLUSION: The CRP/PNI ratio is a novel and useful prognostic score for CSS in patients with resectable ESCC. PMID- 27557505 TI - A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma. AB - Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors. PMID- 27557506 TI - The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation. AB - Septins are a novel class of GTP-binding cytoskeletal proteins evolutionarily conserved from yeast to mammals and have now been found to play a contributing role in a broad range of tumor types. However, their functional importance in breast cancer remains largely unclear. Here, we demonstrated that pharmaceutical inhibition of global septin dynamics would greatly suppress proliferation, migration and invasiveness in breast cancer cell lines. We then examined the expression and subcellular distribution of the selected septins SEPT2 and SEPT7 in breast cancer cells, revealing a rather variable localization of the two proteins with cell cycle progression. To determine the role of both septins in mediating malignant behavior of cancer cells, we used RNA silencing to specifically deplete endogenous SEPT2 or SEPT7 in highly invasive breast cancer cell line MDA-MB-231. Our findings showed that SEPT2/7 depletion had virtually identical inhibitory effects on cellular proliferation, apoptosis, migration and invasion. Moreover, the opposite performance in migration and invasion was observed after enforced expression of SEPT2/7 in the same cell line. We further demonstrated MEK/ERK activation, but not other MAPKs and AKT, was positively correlated with the protein levels of SEPT2 and SEPT7. Additionally, in SEPT2/7 overexpressing cells, the MEK specific inhibitor U0126 was able to correct the high active status of MEK/ERK while normalizing the increased invasive behaviors of these cells. Taken together, these results strongly suggest that SEPT2 and SEPT7 are involved in breast carcinogenesis and may serve as valuable therapeutic targets for breast cancer. PMID- 27557507 TI - Sensitizing thermochemotherapy with a PARP1-inhibitor. AB - Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects. PMID- 27557508 TI - RhoGDIalpha suppresses self-renewal and tumorigenesis of glioma stem cells. AB - Glioma stem cells (GSCs) are a subset of tumor cells that drive glioma initiation and progression. The molecular mechanisms underlying the maintenance of GSCs are still poorly understood. Here we investigated the role of Rho GDP dissociation inhibitor alpha (RhoGDIalpha) in GSCs. RhoGDIalpha was down-regulated in glioma stem cells. Over-expression of RhoGDIalpha suppressed the self-renewal and tumorigenesis of GSCs. Further data showed that RhoGDIalpha inhibited the transcription activity of stem cell marker Oct4. Moreover, inactivation of ROCK1, a downstream effector of RhoGDIalpha, also decreased the self-renewal and Oct4 transcription activity, and rescued the effects caused by RhoGDIalpha knockdown. Our results indicate that RhoGDIalpha is involved in the maintenance of GSCs. PMID- 27557509 TI - CM363, a novel naphthoquinone derivative which acts as multikinase modulator and overcomes imatinib resistance in chronic myelogenous leukemia. AB - Human Chronic Myelogenous Leukemia (CML) is a hematological stem cell disorder which is associated with activation of Bcr-Abl-Stat5 oncogenic pathway. Direct Bcr-Abl inhibitors are initially successful for the treatment of CML but over time many patients develop drug resistance. In the present study, the effects of CM363, a novel naphthoquinone (NPQ) derivative, were evaluated on human CML derived K562 cells. CM363 revealed an effective cell growth inhibition (IC50 = 0.7 +/- 0.5 MUM) by inducing cancer cells to undergo cell cycle arrest and apoptosis. CM363 caused a dose- and time-dependent reduction of cells in G0/G1 and G2/M phases. This cell cycle arrest was associated with increased levels of cyclin E, pChk1 and pChk2 whereas CM363 downregulated cyclin B, cyclin D3, p27, pRB, Wee1, and BUBR1. CM363 increased the double-strand DNA break marker gammaH2AX. CM363 caused a time-dependent increase of annexin V-positive cells, DNA fragmentation and increased number of apoptotic nuclei. CM363 triggered the mitochondrial apoptotic pathway as reflected by a release of cytochrome C from mitochondria and induction of the cleavage of caspase-3 and -9, and PARP. CM363 showed multikinase modulatory effects through an early increased JNK phosphorylation followed by inhibition of pY-Bcrl-Abl and pY-Stat5. CM363 worked synergistically with imatinib to inhibit cell viability and maintained its activity in imatinib-resistant cells. Finally, CM363 (10 mg/Kg) suppressed the growth of K562 xenograft tumors in athymic mice. In summary, CM363 is a novel multikinase modulator that offers advantages to circumvent imanitib resistance and might be therapeutically effective in Bcrl-Abl-Stat5 related malignancies. PMID- 27557510 TI - KLRG1 restricts memory T cell antitumor immunity. AB - Killer cell lectin-like receptor subfamily G member 1 (KLRG1) has been found on human memory T lymphocytes. However, the roles of KLRG1 on human T cells especially in tumor microenvironment have not been fully understood. Our results showed KLRG1 expression on T cells significantly increased in tumor microenvironment. KLRG1+ T cells exhibited poor proliferative capacity with decreased effector cytokine production. Meanwhile, KLRG1+ T cells expressed abundant pro-inflammatory cytokines and demonstrated high level of Foxp3 expression. KLRG1+ T cells showed decreased expression of miRNA-101 and higher expression of CtBP2. Our results indicated KLRG1 might contribute to the impaired antitumor immunity of memory T cells in tumor microenvironment. Thus, repressing KLRG1 on human memory T cells might be a novel therapeutics against cancer. PMID- 27557511 TI - Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline. AB - Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 MUg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3' UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users. PMID- 27557512 TI - CD73 is associated with poor prognosis in HNSCC. AB - CD73 is a cell surface immunosuppressive enzyme involved in tumor progression and metastasis. While patients whose cancer cells express elevated CD73 are typically associated with an unfavorable outcome, the clinical impact of CD73 expression in patients with Head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, we investigated the prognostic significance of CD73 in HNSCC using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with reduced overall survival in patients with HNSCC. We also investigated the functional role of CD73 in vitro and demonstrated that CD73 promotes HNSCC migration and invasion through adenosine A3R stimulation and the activation of EGF/EGFR signaling. Moreover, in vivo xenograft studies demonstrated that CD73 promotes tumorigenesis. In conclusion, our study highlights a role for CD73 as a poor prognostic marker of patient survival and also as a candidate therapeutic target in HNSCCs. PMID- 27557513 TI - Genetic variants of genes in the Notch signaling pathway predict overall survival of non-small cell lung cancer patients in the PLCO study. AB - The Notch signaling pathway has been shown to have biological significance and therapeutic application in non-small cell lung cancer (NSCLC). We hypothesize that genetic variants of genes in the Notch signaling pathway are associated with overall survival (OS) of NSCLC patients. To test this hypothesis, we performed multivariate Cox proportional hazards regression analysis to evaluate associations of 19,571 single nucleotide polymorphisms (SNPs) in 132 Notch pathway genes with OS of 1,185 NSCLC patients available from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We found that five potentially functional tagSNPs in four genes (i.e., ADAM12 rs10794069 A > G, DTX1 rs1732793 G > A, TLE1 rs199731120 C > CA, TLE1 rs35970494 T > TC and E2F3 rs3806116 G > T) were associated with a poor OS, with a variant-allele attributed hazards ratio (HR) of 1.27 [95% confidence interval (95% CI) = 1.13-1.42, P = 3.62E-05], 1.30 (1.14-1.49, 8.16E-05), 1.40 (1.16-1.68, 3.47E-04), 1.27 (1.11 1.44, 3.38E-04), and 1.21 (1.09-1.33, 2.56E-04), respectively. Combined analysis of these five risk genotypes revealed that the genetic score 0-5 was associated with the adjusted HR in a dose-response manner (Ptrend = 3.44E-13); individuals with 2-5 risk genotypes had an adjusted HR of 1.56 (1.34-1.82, 1.46E-08), compared with those with 0-1 risk genotypes. Larger studies are needed to validate our findings. PMID- 27557514 TI - LncRNA ANRIL is up-regulated in nasopharyngeal carcinoma and promotes the cancer progression via increasing proliferation, reprograming cell glucose metabolism and inducing side-population stem-like cancer cells. AB - Long noncoding RNAs play a vital role in diverse biological processes such as embryonic development, cell growth, and tumorigenesis. In this study, we report that LncRNA ANRIL, which encodes a 3834-nt RNA that contains 19 exons at the antisense orientation of the INK4B-ARF-INK4A gene cluster, generally up-regulated in nasopharyngeal carcinoma [1]. In a cohort of 88 NPC patients, ANRIL was highly expressed in advanced-stage cancer. Multivariate analyses revealed that ANRIL expression could serve as an independent predictor of overall survival (P = 0.027) and disease-free survival (P = 0.033). Further investigation showed that knockdown of ANRIL significantly repressed NPC cell proliferation and transformation. We also found that ANRIL could induce the percentage of side population cells (SP cells) in NPC. To meet the urgent needs of energy provision, ANRIL can also reprogram glucose metabolism via increasing glucose uptake for glycolysis, which was regulated by the mTOR signal pathway to affect the expression of essential genes in glycolysis. We concluded that ANRIL could promote NPC progression via increasing cell proliferation, reprograming cell glucose metabolism and inducing side-population stem-like cancer cells. Our results also suggested that ANRIL may serve as a novel diagnostic or prognostic biomarker and a candidate target for new therapies in NPC. PMID- 27557515 TI - Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate. AB - Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL 6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2 mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2 p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes. PMID- 27557516 TI - CK2 targeted RNAi therapeutic delivered via malignant cell-directed tenfibgen nanocapsule: dose and molecular mechanisms of response in xenograft prostate tumors. AB - CK2, a protein serine/threonine kinase, promotes cell proliferation and suppresses cell death. This essential-for-survival signal demonstrates elevated expression and activity in all cancers examined, and is considered an attractive target for cancer therapy. Here, we present data on the efficacy of a tenfibgen (TBG) coated nanocapsule which delivers its cargo of siRNA (siCK2) or single stranded RNA/DNA oligomers (RNAi-CK2) simultaneously targeting CK2alpha and alpha' catalytic subunits. Intravenous administration of TBG-siCK2 or TBG-RNAi CK2 resulted in significant xenograft tumor reduction at low doses in PC3-LN4 and 22Rv1 models of prostate cancer. Malignant cell uptake and specificity in vivo was verified by FACS analysis and immunofluorescent detection of nanocapsules and PCR detection of released oligomers. Dose response was concordant with CK2alphaalpha' RNA transcript levels and the tumors demonstrated changes in CK2 protein and in markers of proliferation and cell death. Therapeutic response corresponded to expression levels for argonaute and GW proteins, which function in oligomer processing and translational repression. No toxicity was detected in non-tumor tissues or by serum chemistry. Tumor specific delivery of anti-CK2 RNAi via the TBG nanoencapsulation technology warrants further consideration of translational potential. PMID- 27557517 TI - The double benefit of Spalax p53: surviving underground hypoxia while defying lung cancer cells in vitro via autophagy and caspase-dependent cell death. AB - The blind subterranean mole rat, Spalax ehrenbergi, is a model organism for hypoxia tolerance. This superspecies have adapted to severe environment by altering an array of hypoxia-mediated genes, among which an alteration in the p53 DNA binding domain (corresponding to R174K in humans) that hinders its transcriptional activity towards apoptotic genes. It is well accepted that apoptosis is not the only form of programmed cell death and that mechanisms that depend on autophagy are also involved. In the current work we have extended our research and investigated the possibility that Spalax p53 can activate autophagy. Using two complementary assays, we have established that over-expression of the Spalax p53 in p53-null cells (human lung cancer cells, H1299), potently induces autophagy. As Spalax is considered highly resistant to cancer, we further studied the relative contribution of autophagy on the outcome of H1299 cells, following transfection with Spalax p53. Results indicate that Spalax p53 acts as a tumor suppressor in lung cancer cells, inducing cell death that involves autophagy and caspases and inhibiting cell number, which is exclusively caspase-dependent. To conclude, the Spalax p53 protein was evolutionary adapted to survive severe underground hypoxia while retaining the ability to defy lung cancer. PMID- 27557518 TI - IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway. AB - NOD1 (nucleotide-binding oligomerization domain 1) is overexpressed in head and neck squamous cell carcinoma (HNSCC) cells, as is IL-8 in cancer cells. However, the mechanism of the IL-8-mediated overexpression of NOD in HNSCC not been identified. This study determines whether IL-8 promotes tumor progression via the NOD signaling pathway in HNSCC. Higher IL-8, NOD1 and receptor-interacting protein kinase (RIP2) expressions were observed in HNSCC tissue than in non cancerous matched tissue (NCMT), whereas NOD2 was weakly expressed. Furthermore, IL-8 stimulated the proliferation of HNSCC cells (SCC4, SCC9 and SCC25) but not dysplastic oral mucosa DOK cells. Exposure to IL-8 increased the clonogenicity of HNSCC cells. IL-8 siRNA inhibited cell proliferation and cell colony formation, suggesting that IL-8 is involved in HNSCC cancer progression. The expressions of CXCR1 and CXCR2 were higher in HNSCC tissue than in NCMT. HNSCC cells that were exposed to IL-8 exhibited higher expression of CXCR1/2 than did controls. The blocking of IL-8 by siRNA reduced CXCR1/2 expression in HNSCC cells, suggesting that the cancer progression of HNSCC cells that is induced by IL-8 depends on CXCR1/2. Additionally, IL-8 is associated with increased NOD1 and RIP2 expression and reduced NOD2 expression in three types of HNSCC cells. The blocking of IL-8 by siRNA reduces IL-8, NOD1 and RIP2 expressions in HNSCC cells, but not the level of NOD2. These results suggest that IL-8 has an important role in HNSCC progression via a CXCR1/2-meidated NOD1/RIP2 signaling pathway. PMID- 27557519 TI - The accuracy of microRNA-210 in diagnosing lung cancer: a systematic review and meta-analysis. AB - Studies examining the diagnostic value of microRNA-210 for lung cancer have yielded inconsistent results. Here, we performed a meta-analysis to assess the diagnostic accuracy of microRNA-210 for lung cancer. Nine eligible studies involving 993 patients (554 lung cancer patients and 439 non-cancer patients) were independently identified, and the quality of these studies was assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.66 (95% CI, 0.57 to 0.75), 0.82 (95% CI, 0.72 to 0.89), 3.64 (95% CI, 2.54 to 5.21), 0.41 (95% CI, 0.34 to 0.51) and 8.78 (95% CI, 6.10 to 12.66), respectively. The area under the summary receiver operator characteristic curve was 0.80 (95% CI, 0.76 to 0.83). These results indicated that microRNA-210 had moderate diagnostic value for lung cancer. Additional prospective studies are needed to confirm the diagnostic value of microRNA-210. PMID- 27557520 TI - Synergistic effect of reduced polypeptide micelle for co-delivery of doxorubicin and TRAIL against drug-resistance in breast cancer. AB - Cationic peptides as a non-viral gene vector have become a hotspot of research because of their high transfection efficcacy and safety. Based on our previous study, we synthesized a cationic reduction-responsive vector based on disulfide cross-linked L-arginine, L-histidine and lipoic acid (LHRss) as the co-carrier of both doxorubicin (DOX) and the necrosis factor-related apoptosis-inducing ligand (pTRAIL). The LHRss/DOX/TRAIL construct has reduction-sensitive behavior and an enhanced endosomal escape ability to increase the cytotoxicity of DOX and the transfection efficiency. Further, the LHRss/DOX/TRAIL construct increased the accumulation of DOX and promoted the expression of pTRAIL, thus increasing cellular apoptosis by 83.7% in MCF-7/ADR cells. In addition, the in vivo biodistribution results showed that the LHRss/DOX/TRAIL construct could target tumors well. The in vivo anti-tumor effect study demonstrated that the LHRss/DOX/TRAIL construct inhibited tumor growth markedly, with a tumor inhibitory rate of 94.0%. The co-delivery system showed a significant synergistic anti-tumor effect. The LHRss/DOX/TRAIL construct may prove to be a promising co delivery vector for the effective treatment of drug resistant breast cancer. PMID- 27557521 TI - Activation of HERV-K Env protein is essential for tumorigenesis and metastasis of breast cancer cells. AB - Human endogenous retrovirus type K (HERV-K) Env protein was previously demonstrated to be overexpressed in human breast cancer (BC) cells and tissues. However, the molecular pathways driving the specific alterations are unknown. We now show that knockdown of its expression with an shRNA (shRNAenv) blocked BC cell proliferation, migration, and invasion. shRNAenv transduction also attenuated the ability of BC cells to form tumors, and notably prevented metastasis. Mechanistically, downregulation of HERV-K blocked expression of tumor associated genes that included Ras, p-RSK, and p-ERK. The major upstream regulators influenced by HERV-K knockdown were p53, TGF- beta1, and MYC. Of interest, when the HERV-K env gene was overexpressed in shRNAenv-transduced BC cells using an HERV-K env expression vector, Ras/Raf/MEK/ERK pathway signaling was restored. CDK5, which alters p53 phosphorylation in some cancers, was upregulated and p53 was downregulated when HERV-K was overexpressed. CDK5 is also a mediator of TGF-beta1-induced epithelial-mesenchymal transition and migration in cancer cells, and is involved in tumor formation. Importantly, reductions in migration, invasion, and transformation of BC cells stably transduced with shRNAenv was reversed after adding back a vector with a synonymous mutation of HERV-K env. Taken together, these results indicate that HERV-K Env protein plays an important role in tumorigenesis and metastasis of BC. PMID- 27557522 TI - Selenoprotein W redox-regulated Ca2+ channels correlate with selenium deficiency induced muscles Ca2+ leak. AB - Selenium (Se) deficiency induces Ca2+ leak and calcification in mammal skeletal muscles; however, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and selenoprotein W (SelW) gene knockdown myoblast and embryo models were used to study the mechanism. The results showed that Se deficiency-induced typical muscular injuries accompanied with Ca2+ leak and oxidative stress (P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca2+ channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 (P < 0.05); and increased the levels of Ca2+ channel PMCA (P < 0.05). Similarly, SelW knockdown also induced Ca2+ leak from the SR and cytoplasm; increased mitochondrial Ca2+ levels and oxidative stress; injured SR and mitochondrial ultrastructure; decreased levels of SLC8A, CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca2+ channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdown induced Ca2+ leak, oxidative stress, and Ca2+ channel reduction. In addition, Ca2+ levels and the expression of the Ca2+ channels, RyR1, SERCA, CACNA1S, TRPC1, and TRPC3 were recovered to normal levels by N-acetyl-L-cysteine (NAC) treatment compared with SelW knockdown cells. Thus, with regard to the decreased Ca2+ channels, SelW knockdown closely correlated Se deficiency with Ca2+ leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca2+ leak in muscles. PMID- 27557524 TI - Author Replies. PMID- 27557523 TI - Early response to neoadjuvant chemotherapy can help predict long-term survival in patients with cervical cancer. AB - It is still controversial whether cervical cancer patients with clinical responses after neoadjuvant chemotherapy (NACT) have a better long-term survival or not. This study was designed to investigate the effect of the clinical response on the disease-free survival (DFS) of cervical cancer patients undergoing NACT. A total of 853 patients from a retrospective study were used to evaluate whether the clinical response was an indicator for the long-term response, and 493 patients from a prospective cohort study were used for further evaluation. The survival difference was detected by log-rank test, univariate and multivariate Cox regression and a pooled analysis. The log-rank test revealed that compared with non-responders, the DFS of responders was significantly higher in the retrospective data (P = 0.007). Univariate Cox regression showed that the clinical response was an indicator of long-term survival in the retrospective study (HR 1.83, 95% CI 1.18-2.85, P = 0.007). In a multivariate Cox model, the clinical response was still retained as an independent significant prognostic factor in the retrospective study (HR 1.59, 95% CI 1.01-2.50, P = 0.046). The result was also validated in the prospective data with similar results. These findings implied that the clinical response can be regarded as an independent predictor of DFS. PMID- 27557525 TI - Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene. AB - To maximise the efficiency of template-dependent gene editing, most studies describe programmable and/or RNA-guided endonucleases that make a double-stranded break at, or close to, the target sequence to be modified. The rationale for this design strategy is that most gene repair tracts will be very short. Here, we describe a CRISPR Cas9/gRNA selection-free strategy which uses deep sequencing to characterise repair tracts from a donor plasmid containing seven nucleotide differences across a 216 bp target region in the human CFTR gene. We found that 90% of the template-dependent repair tracts were >100 bp in length with equal numbers of uni-directional and bi-directional repair tracts. The occurrence of long repair tracts suggests that a single gRNA could be used with variants of the same template to create or correct specific mutations within a 200 bp range, the size of ~80% of human exons. The selection-free strategy used here also allowed detection of non-homologous end joining events in many of the homology-directed repair tracts. This indicates a need to modify the donor, possibly by silent changes in the PAM sequence, to prevent creation of a second double-stranded break in an allele that has already been correctly edited by homology-directed repair. PMID- 27557526 TI - Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review. AB - Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted. PMID- 27557527 TI - Clinical importance of the antibiotic regimen in transrectal ultrasound-guided biopsy: quinolone versus cephalosporin. AB - BACKGROUND: Quinolone is recommended as an antimicrobial prophylaxis to prevent infectious complication after transrectal ultrasound-guided biopsy, but the increased appearance of quinolone-resistant organism has raised concerns about the efficacy of quinolone. The current study was performed to evaluate various clinical factors including antimicrobial regimens associated with infectious complication after transrectal ultrasound-guided prostate biopsy. METHODS: The medical records of 5215 patients who underwent a multicore transrectal ultrasound guided prostate biopsy between May 2003 and January 2013 at our institution were reviewed. We analyzed clinical variables including prostate-specific antigen, International Prostate Symptom Score, antimicrobial regimen, prostate size, and number of biopsy cores. Univariate and multivariate logistic regression analyses of infection-related hospitalization after prostate biopsy were performed. RESULTS: The mean age and median prostate-specific antigen of the entire cohort were 66 years and 6.4 ng/ml, respectively. Twenty-eight (0.54 %) patients developed an infectious complication after prostate biopsy that required hospitalization. Patients who received prophylactic quinolone showed a higher infectious hospitalization rate than patients who received prophylactic third generation cephalosporin (1.5 vs. 0.3 %; p < 0.001). Multivariate logistic regression analysis demonstrated that the International Prostate Symptom Score (odds ratio = 3.18, 95 % confidence interval 1.24-8.13, p = 0.016) and the use of third-generation cephalosporin (odds ratio = 0.21, 95 % confidence interval 0.10 0.44, p < 0.001) were independent predictors of infection-related hospitalization after prostate biopsy. CONCLUSION: With the emergence of quinolone-resistant microorganisms, third-generation cephalosporin may effectively reduce the risk of infectious complications after transrectal ultrasound-guided prostate biopsy. Severe lower urinary tract symptoms may also be an independent risk factor for infection-related hospitalization after transrectal ultrasound-guided prostate biopsy. PMID- 27557528 TI - Continuous weeklong measurements of indoor particle levels in a Minnesota Tribal Casino Resort. AB - BACKGROUND: Secondhand smoke (SHS) exposure for workers and patrons in hospitality venues is a persistent and significant public health concern. We designed this study to provide a comprehensive assessment of SHS exposure inside an Indian Tribal Casino in Minnesota. METHODS: Real-time fine particulate matter (PM2.5) concentrations were measured at multiple locations for up to 7 days. The field monitoring provided information on the day of week and time of day variation of SHS exposure, as well as comparisons between smoking and non-smoking areas. RESULTS: Indoor PM2.5 level was nearly 13 times the concurrent outdoor PM2.5 level. Gaming floor hourly PM2.5 level was highest on Saturday night, averaged at 62.9 MUg/m(3). Highest PM2.5 concentration was observed in smoking permitted employee break room, reaching 600 MUg/m(3). PM2.5 readings in non smoking sections exhibited same temporal pattern as the readings in smoking sections. CONCLUSIONS: The results show that indoor concentration of PM2.5 is substantially higher than the outdoor level, posing health risks to casino workers and patrons. SHS can migrate into adjacent non-smoking areas very quickly. The casino's ventilation system did not fully eliminate SHS. A completely smoke-free casino would be the only way to fully protect non-smoking patrons and employees from the dangers of tobacco smoke. PMID- 27557529 TI - Comparative heel stick study showed that newborn infants who had undergone repeated painful procedures showed increased short-term pain responses. AB - AIM: We evaluated the short-term effect of repeated pain exposure on the pain responses of newborn infants using different pain assessment methods, as this area had been under-researched. METHODS: We compared 20 term, large for gestational age infants and 40 term, appropriate for gestational age controls. All had undergone a heel stick for a newborn screening test just before discharge, but the larger babies had also undergone at least other five painful stimuli prior to that. A pulse oximeter and a skin conductance algesimeter (SCA) were connected to the babies during the heel prick, and video recordings were made. Crying time, the Neonatal Infant Pain Scale (NIPS), heart rate, peripheral oxygen saturation (SpO2 ) and SCA measurements were compared within and between the groups. RESULTS: After the heel prick, the crying time (p = 0.021) and NIPS (p = 0.013) scores were significantly higher in the study group and the SpO2 levels were significantly lower (p = 0.009), but the heart rate (p = 0.981) was not significantly different between the groups. SCA measurements did not differ significantly between the groups. CONCLUSION: Babies who received more painful stimuli during the first few days of life showed greater pain responses during a subsequent heel prick. PMID- 27557530 TI - Iatrogenic aortic dissection after minimally invasive aortic valve replacement: a case report. AB - BACKGROUND: As minimally invasive cardiac and vascular procedures are on the rise, the incidence of iatrogenic acute aortic dissection (IAAD) will increase. Cardiovascular professionals should be aware about the risk factors, means of prevention and best management options for IAAD in the perioperative setting. CASE PRESENTATION: We present the successful clinical management of a complicated case of IAAD after minimally invasive aortic valve replacement. CONCLUSION: High index of suspicion is required for prompt diagnosis of IAAD; collaboration of the whole perioperative team is imperative for management of this catastrophe. PMID- 27557531 TI - Psychological distress in medical patients 30 days following an emergency department admission: results from a prospective, observational study. AB - BACKGROUND: Psychological distress in medical patients admitted to the emergency department (ED) is not well studied. Our aim was to investigate the extent of psychological distress in a broad and unselected medical patient sample 30 days after ED admission and its association with socio-demographic and clinical variables. METHOD: We used data from a prospective observational cohort study including 1575 consecutive adult medical patients presenting to the ED with acute somatic conditions. Outcome variables were patient's psychological distress measured by the 4-item Patient Health Questionnaire (PHQ-4) and self-rated health assessed 30 days after ED admission using telephone interviews. Risk factors included socio-demographic variables (e.g. gender, marital status), clinical presentation (e.g. illness severity, main initial diagnosis) and course of illness (e.g. rehospitalisation, length of hospital stay). RESULTS: A total of 38 % of patients had evidence for psychological distress 30 days after ED admission. Multivariate analysis found female gender (adjusted odds ratio [aOR] 1.35, 95 % confidence interval [CI] 1.02 to 1.78), comorbid psychiatric disorder (aOR 1.63, 95 % CI 1.08 to 2.62), discharge to a post-acute care institution (aOR 1.47, 95 % CI 1.03 to 2.09), unplanned rehospitalisation (aOR 2.38, 95 % CI 1.47 to 3.86), and unplanned visit at general practitioner (aOR 4.75, 95 % CI 2.57 to 8.80) to be associated with distress at day 30 following ED admission. CONCLUSIONS: One month after ED admission a significant number of patients still show a moderate amount of psychophysical distress. Strongest related variables were course of illness, in particular unplanned general practitioner visits. Future interventional studies should assess possibilities to reduce distress in patients at increased risk. TRIAL REGISTRATION: NCT01768494 , January 9, 2013 (registration date), February 25, 2013 (enrolment of first participant). PMID- 27557532 TI - The Role of Glucose and Lipid Metabolism in Growth and Survival of Cancer Cells. AB - One of the prerequisites for cell growth and proliferation is the synthesis of macromolecules, including proteins, nucleic acids and lipids. Cells have to alter their metabolism to allow the production of metabolic intermediates that are the precursors for biomass production. It is now evident that oncogenic signalling pathways target metabolic processes on several levels and metabolic reprogramming has emerged as a hallmark of cancer. The increased metabolic demand of cancer cells also produces selective dependencies that could be targeted for therapeutic intervention. Understanding the role of glucose and lipid metabolism in supporting cancer cell growth and survival is crucial to identify essential processes that could provide therapeutic windows for cancer therapy. PMID- 27557533 TI - Lactate-An Integrative Mirror of Cancer Metabolism. AB - The technique of induced metabolic bioluminescence imaging (imBI) has been developed to obtain a "snapshot" of the momentary metabolic status of biological tissues. Using cryosections of snap-frozen tissue specimens, imBI combines highly specific and sensitive in situ detection of metabolites with a spatial resolution on a microscopic level and with metabolic imaging in relation to tissue histology. Here, we present the application of imBI in human colorectal cancer. Comparing the metabolic information of one biopsy with that of 2 or 3 biopsies per individual cancer, the classification into high versus low lactate tumors, reflecting different glycolytic activities, based on a single biopsy was in agreement with the result from multiple biopsies in 83 % of all cases. We further demonstrate that the metabolic status of tumor tissue can be preserved at least over 10 years by storage in liquid nitrogen, but not by storage at -80 degrees C. This means that tissue banking with long-term preservation of the metabolic status is possible at -180 degrees C, which may be relevant for studies on long term survival of cancer patients. As with other tumor entities, tissue lactate concentration was shown to be correlated with tumor development and progression in colorectal cancer. At first-time diagnosis, lactate values were low in rectal normal tissue and adenomas, were significantly elevated to intermediate levels in non-metastatic adenocarcinomas, and were very high in carcinomas with distant metastasis. There was an inverse behavior of tissue glucose concentration under corresponding conditions. The expression level of monocarboxylate transporter-4 (MCT4) was positively correlated with the tumor lactate concentration and may thus contribute to high lactate tumors being associated with a high degree of malignancy. PMID- 27557534 TI - Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer. AB - In the past decade, there has been a resurgence of interest in elucidating how metabolism is altered in cancer cells and how such dependencies can be targeted for therapeutic gain. At the core of this research is the concept that metabolic pathways are reprogrammed in cancer cells to divert nutrients toward anabolic processes to facilitate enhanced growth and proliferation. Importantly, physiological cellular signaling mechanisms normally tightly regulate the ability of cells to gain access to and utilize nutrients, posing a fundamental barrier to transformation. This barrier is often overcome by aberrations in cellular signaling that drive tumor pathogenesis by enabling cancer cells to make critical cellular decisions in a cell-autonomous manner. One of the most frequently altered pathways in human cancer is the PI3K-Akt-mTOR signaling pathway. Here, we describe mechanisms by which this signaling network is responsible for controlling cellular metabolism. Through both the post-translational regulation and the induction of transcriptional programs, the PI3K-Akt-mTOR pathway coordinates the uptake and utilization of multiple nutrients, including glucose, glutamine, nucleotides, and lipids, in a manner best suited for supporting the enhanced growth and proliferation of cancer cells. These regulatory mechanisms illustrate how metabolic changes in cancer are closely intertwined with oncogenic signaling pathways that drive tumor initiation and progression. PMID- 27557535 TI - MYC, Metabolic Synthetic Lethality, and Cancer. AB - The MYC oncogene plays a pivotal role in the development and progression of human cancers. It encodes a transcription factor that has broad reaching effects on many cellular functions, most importantly in driving cell growth through regulation of genes involved in ribosome biogenesis, metabolism, and cell cycle. Upon binding DNA with its partner MAX, MYC recruits factors that release paused RNA polymerases to drive transcription and amplify gene expression. At physiologic levels of MYC, occupancy of high-affinity DNA-binding sites drives 'house-keeping' metabolic genes and those involved in ribosome and mitochondrial biogenesis for biomass accumulation. At high oncogenic levels of MYC, invasion of low-affinity sites and enhancer sequences alter the transcriptome and cause metabolic imbalances, which activates stress response and checkpoints such as p53. Loss of checkpoints unleashes MYC's full oncogenic potential to couple metabolism with neoplastic cell growth and division. Cells that overexpress MYC, however, are vulnerable to metabolic perturbations that provide potential new avenues for cancer therapy. PMID- 27557536 TI - The Role of pH Regulation in Cancer Progression. AB - Frequently observed phenotypes of tumours include high metabolic activity, hypoxia and poor perfusion; these act to produce an acidic microenvironment. Cellular function depends on pH homoeostasis, and thus, tumours become dependent on pH regulatory mechanisms. Many of the proteins involved in pH regulation are highly expressed in tumours, and their expression is often of prognostic significance. The more acidic tumour microenvironment also has important implications with regard to chemotherapeutic and radiotherapeutic interventions. In addition, we review pH-sensing mechanisms, the role of pH regulation in tumour phenotype and the use of pH regulatory mechanisms as therapeutic targets. PMID- 27557537 TI - Metabolic Features of Cancer Treatment Resistance. AB - A major barrier to achieving durable remission and a definitive cure in oncology patients is the emergence of tumor resistance, a common outcome of different disease types, and independent from the therapeutic approach undertaken. In recent years, subpopulations of slow-cycling cells endowed with enhanced tumorigenic potential and multidrug resistance have been isolated in different tumors, and mounting experimental evidence suggests these resistant cells are responsible for tumor relapse. An in-depth metabolic characterization of resistant tumor stem cells revealed that they rely more on mitochondrial respiration and less on glycolysis than other tumor cells, a finding that challenges the assumption that tumors have a primarily glycolytic metabolism and defective mitochondria. The demonstration of a metabolic program in resistant tumorigenic cells that may be present in the majority of tumors has important therapeutic implications and is a critical consideration as we address the challenge of identifying new vulnerabilities that might be exploited therapeutically. PMID- 27557538 TI - Tissue-Based Metabolomics to Analyze the Breast Cancer Metabolome. AB - Mass spectrometry and nuclear magnetic resonance-based metabolomics have been developed into mature technologies that can be utilized to analyze hundreds of biological samples in a high-throughput manner. Over the past few years, both technologies were utilized to analyze large cohorts of fresh frozen breast cancer tissues. Metabolite biomarkers were shown to separate breast cancer tissues from normal breast tissues with high sensitivity and specificity. Furthermore, the metabolome differed between hormone receptor positive (HR+) and hormone receptor negative (HR-) breast cancer, but was unchanged in HER2+ tumors compared to HER2- tumors. New metabolism-related biomarkers were discovered including the 4 aminobutyrate aminotransferase ABAT, where low mRNA expression led to an accumulation of beta-alanine and shortened relapse-free survival. The glutamate to-glutamine ratio (GGR) represents another new biomarker that was increased in 88 % of HR- tumors and 56 % of HR+ tumors compared to normal breast tissues. The GGR might help to stratify patients for the treatment with specific glutaminase inhibitors that were recently developed and are currently being tested in phase I clinical studies. Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. In summary, metabolomics analysis of breast cancer tissues is a reliable method and has produced many new biological insights that may impact breast cancer diagnostics and treatment over the coming years. PMID- 27557539 TI - Imaging of Tumor Metabolism Using Positron Emission Tomography (PET). AB - Molecular imaging employing PET/CT enables in vivo visualization, characterization, and measurement of biologic processes in tumors at a molecular and cellular level. Using specific metabolic tracers, information about the integrated function of multiple transporters and enzymes involved in tumor metabolic pathways can be depicted, and the tracers can be directly applied as biomarkers of tumor biology. In this review, we discuss the role of F-18 fluorodeoxyglucose (FDG) as an in vivo glycolytic marker which reflects alterations of glucose metabolism in cancer cells. This functional molecular imaging technique offers a complementary approach to anatomic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) and has found widespread application as a diagnostic modality in oncology to monitor tumor biology, optimize the therapeutic management, and guide patient care. Moreover, emerging methods for PET imaging of further biologic processes relevant to cancer are reviewed, with a focus on tumor hypoxia and aberrant tumor perfusion. Hypoxic tumors are associated with poor disease control and increased resistance to cytotoxic and radiation treatment. In vivo imaging of hypoxia, perfusion, and mismatch of metabolism and perfusion has the potential to identify specific features of tumor microenvironment associated with poor treatment outcome and, thus, contribute to personalized treatment approaches. PMID- 27557540 TI - Quantitative Analysis of Cancer Metabolism: From pSIRM to MFA. AB - Metabolic reprogramming is a required step during oncogenesis and essential for cellular proliferation. It is triggered by activation of oncogenes and loss of tumor suppressor genes. Beside the combinatorial events leading to cancer, common changes within the central metabolism are reported. Increase of glycolysis and subsequent lactic acid formation has been a focus of cancer metabolism research for almost a century. With the improvements of bioanalytical techniques within the last decades, a more detailed analysis of metabolism is possible and recent studies demonstrate a wide range of metabolic rearrangements in various cancer types. However, a systematic and mechanistic understanding is missing thus far. Therefore, analytical and computational tools have to be developed allowing for a dynamic and quantitative analysis of cancer metabolism. In this chapter, we outline the application of pulsed stable isotope resolved metabolomics (pSIRM) and describe the interface toward computational analysis of metabolism. PMID- 27557541 TI - Mathematical Modeling of Cellular Metabolism. AB - Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research. PMID- 27557542 TI - Ketogenic Diet and Cancer-a Perspective. AB - Research of the last two decades showed that chronic low-grade inflammation, elevated blood glucose and insulin levels may play role in the onset of a number of non-communicable diseases such as type 2 diabetes and some forms of cancer. Regular exercise and fasting can ameliorate high blood glucose and insulin levels as well as increase the concentration of plasma ketone bodies. These, in consequence, may lead to reduction of inflammation. Exercise or severe restriction of caloric intake is not always advisable for patients, in particular those suffering from cancer. The ketogenic diet (KD), characterized by high fat, moderate protein and very low carbohydrate composition can evoke a physiological state similar to that triggered by exercise or fasting. These attributes of KD prompted its possible use in treatment of a number of metabolic diseases, including several types of malignancies. Although results from clinical studies employing KD in the treatment of cancer are still limited, the results obtained from animal models are encouraging and show that KD presents a viable option as an adjunct therapy for cancer. PMID- 27557543 TI - Fasting and Caloric Restriction in Cancer Prevention and Treatment. AB - Cancer is the second leading cause of death in the USA and among the leading major diseases in the world. It is anticipated to continue to increase because of the growth of the aging population and prevalence of risk factors such as obesity, smoking, and/or poor dietary habits. Cancer treatment has remained relatively similar during the past 30 years with chemotherapy and/or radiotherapy in combination with surgery remaining the standard therapies although novel therapies are slowly replacing or complementing the standard ones. According to the American Cancer Society, the dietary recommendation for cancer patients receiving chemotherapy is to increase calorie and protein intake. In addition, there are no clear guidelines on the type of nutrition that could have a major impact on cancer incidence. Yet, various forms of reduced caloric intake such as calorie restriction (CR) or fasting demonstrate a wide range of beneficial effects able to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories are emerging as interventions with the potential to be widely used to prevent and treat cancer. Here, we review preclinical and preliminary clinical studies on dietary restriction and fasting and their role in inducing cellular protection and chemotherapy resistance. PMID- 27557544 TI - Multiscale dispersion-state characterization of nanocomposites using optical coherence tomography. AB - Nanocomposite materials represent a success story of nanotechnology. However, development of nanomaterial fabrication still suffers from the lack of adequate analysis tools. In particular, achieving and maintaining well-dispersed particle distributions is a key challenge, both in material development and industrial production. Conventional methods like optical or electron microscopy need laborious, costly sample preparation and do not permit fast extraction of nanoscale structural information from statistically relevant sample volumes. Here we show that optical coherence tomography (OCT) represents a versatile tool for nanomaterial characterization, both in a laboratory and in a production environment. The technique does not require sample preparation and is applicable to a wide range of solid and liquid material systems. Large particle agglomerates can be directly found by OCT imaging, whereas dispersed nanoparticles are detected by model-based analysis of depth-dependent backscattering. Using a model system of polystyrene nanoparticles, we demonstrate nanoparticle sizing with high accuracy. We further prove the viability of the approach by characterizing highly relevant material systems based on nanoclays or carbon nanotubes. The technique is perfectly suited for in-line metrology in a production environment, which is demonstrated using a state-of-the-art compounding extruder. These experiments represent the first demonstration of multiscale nanomaterial characterization using OCT. PMID- 27557545 TI - Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett's Esophagus Than in Healthy Controls. AB - Background/Aims: Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett's esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett's esophagus to that in healthy controls. Methods: A total of 26 patients with histology-confirmed Barrett's esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. Results: Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 +/- 0.74 vs 1.19 +/- 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pH-measurement and acid clearance test were not correlated (all P > 0.3). Conclusions: More frequent swallowing and thus faster acid clearance in Barrett's esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes. PMID- 27557546 TI - Risk assessment of gene variants for neonatal hyperbilirubinemia in Taiwan. AB - BACKGROUND: Hyperbilirubinemia is a common disorder during neonatal period in Taiwan. Gene variants may play an important role in the development of neonatal hyperbilirubinemia. The current study investigated the association between neonatal hyperbilirubinemia and common gene variants involving the production and metabolism of bilirubin. METHODS: This prospective study enrolled 444 healthy infants born in the Chang Gung Memorial Hospital at Taipei from 2013-2015. Hyperbilirubinemia was defined as a total bilirubin >= 15 mg/dL. A log-binomial model was used to assess the risk of gene variants. RESULTS: The most common genetic variant was short heme oxygenase (HO)-1 promoter GT-allele (<24 repeats) (39.4 %), followed by GA at nt388 in hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) (31.1 %), GA at nt211 in UDP-glucuronosyltransferase 1A1 (UGT1A1) (29.3 %), ABO incompatibility (16.2 %), alpha thalassemia (5.0 %), and G6PD deficiency (3.2 %). The log-binomial analysis demonstrated greater risks of hyperbilirubinemia in infants with GA at nt211 in UGT1A1 (RR = 1.548; 95 % CI = 1.096-2.187), short HO-1 promoter GT-repeat (RR = 2.185; 95 % CI = 1.527 3.125), and G6PD deficiency (RR = 1.985; 95 % CI = 1.010-3.901). The other gene variants - including blood type, alpha thalassemia, and SLCO1B1 - carried no significant risk. CONCLUSIONS: G6PD deficiency, short HO-1 promoter GT-repeat and GA at nt211 in UGT1A1 are risk factors of neonatal hyperbilirubinemia. The data provide clinical evidence to explain the high incidence of neonatal hyperbilirubinemia in Taiwan. PMID- 27557547 TI - A pan-coronary artery angiographic study of the association between diabetes mellitus and progression or regression of coronary atherosclerosis. AB - The frequency and pattern of progression or regression of coronary atherosclerosis in contemporary patients with diabetes remain unknown. This study included 605 patients with coronary artery disease (CAD). Two coronary angiographic examinations at baseline and after 2 years were performed. The analysis focused on non-stented segments with diameter stenosis >=25 %. Atherosclerosis progression (or regression) was defined as a decrease (or increase) in the mean minimal lumen diameter (MLD) in the 2-year angiogram compared to mean MLD in the baseline angiogram of >0.2 mm. Statins were prescribed in 576 patients (95.2 %). The primary outcome was atherosclerosis progression or regression in the 2-year angiogram. One hundred sixty-nine patients (28 %) had diabetes. Diabetic patients had greater reduction of mean MLD in the 24 angiogram compared to baseline angiogram than nondiabetic patients (0.11 +/- 0.18 vs. -0.08 +/- 0.15 mm, P < 0.001). Atherosclerosis progression was observed in 37 patients with diabetes and 16 nondiabetic patients (21.9 vs. 3.7 %; P < 0.001). Atherosclerosis regression was observed in two diabetic patients and 78 nondiabetic patients (1.2 vs. 17.9 %; P < 0.001). A progression pattern across all coronary segments was observed in 70 patients (41.4 %) with diabetes and 60 patients (13.8 %) without diabetes (P < 0.001). Diabetic patients with a low-density lipoprotein cholesterol >=70 mg/dl showed more atherosclerosis progression than diabetic patients with LDL cholesterol <70 mg/dl (delta-MLD: 0.12 +/- 0.19 vs. 0.08 +/- 0.16 mm; P = 0.04). In conclusion, in contemporary patients with CAD treated with moderate-intensity statin therapy, diabetes is associated with the increased risk of progression and decreased probability of regression of coronary atherosclerosis. PMID- 27557548 TI - Inverse relationship between erythrocyte size and platelet reactivity in elderly. AB - Previous work indicates that erythrocytes (RBCs) accumulate beta-amyloid X-40 (Abeta40) in individuals with Alzheimer disease (AD) and to a lesser extent in healthy elderly. The toxin damages RBCs and increases their mean corpuscular volume (MCV). Furthermore, AD platelets demonstrate lower reactivity. This study investigated interactions between RBCs and platelets. Older individuals with moderate hypertension (n = 57) were classified into two groups, depending on MCV in whole blood: The MCVhigh group comprised individuals with higher MCV (n = 27; 97 +/- 3(SD) fl) and MCVlow group had relatively lower MCV (n = 30; 90 +/- 3(SD) fl). Flow cytometry was used to determine platelet reactivity, i.e., the surface binding of fibrinogen after provocation. Adenosine diphosphate (ADP) and a thrombin receptor-activating protein (TRAP-6) were used as agonists. Subsequently, blood cells were divided according to density into 17 subfractions. Intra-RBC Abeta40 content was analyzed and in all platelet populations surface bound fibrinogen was determined to estimate platelet in vivo activity. We found Abeta40 inside RBCs of approximately 50% of participants, but the toxin did not affect MCV and platelet reactivity. In contrast, MCV associated inversely with platelet reactivity as judged from surface-attached fibrinogen after ADP (1.7 MUmol/L) (p < 0.05) and TRAP-6 provocation (57 MUmol/L (p = 0.01) and 74 MUmol/L (p < 0.05)). In several density fractions (nos. 3, 4, 8, 11-13 (p < 0.05) and nos. 5-7 (p < 0.01)) MCV linked inversely with platelet-attached fibrinogen. In our community-dwelling sample, enhanced MCV associated with decreased platelet reactivity and lower in vivo platelet activity. It resembles RBCs and platelet behavior in AD-type dementia. PMID- 27557549 TI - Predictors of Problem Gambling in the U.S. AB - In this article we examine data from a national U.S. adult survey of gambling to determine correlates of problem gambling and discuss them in light of theories of the etiology of problem gambling. These include theories that focus on personality traits, irrational beliefs, anti-social tendencies, neighborhood influences and availability of gambling. Results show that males, persons in the 31-40 age range, blacks, and the least educated had the highest average problem gambling symptoms. Adults who lived in disadvantaged neighborhoods also had the most problem gambling symptoms. Those who attended religious services most often had the fewest problem gambling symptoms, regardless of religious denomination. Respondents who reported that it was most convenient for them to gamble had the highest average problem gambling symptoms, compared to those for whom gambling was less convenient. Likewise, adults with the personality traits of impulsiveness and depression had more problem gambling symptoms than those less impulsive or depressed. Respondents who had friends who approve of gambling had more problem gambling symptoms than those whose friends did not approve of gambling. The results for the demographic variables as well as for impulsiveness and religious attendance are consistent with an anti-social/impulsivist pathway to problem gambling. The results for depression are consistent with an emotionally vulnerable pathway to problem gambling. PMID- 27557550 TI - Regional Differences in Serotonin Transporter Occupancy by Escitalopram: An [11C]DASB PK-PD Study. AB - BACKGROUND AND OBJECTIVE: Escitalopram is one of the most commonly prescribed selective serotonin reuptake inhibitors (SSRIs). It is thought to act by blocking the serotonin transporter (SERT). However, its dose-SERT occupancy relationship is not well known, so it is not clear what level of SERT blockade is achieved by currently approved doses. METHODS: To determine the dose-occupancy relationship, we measured serial SERT occupancy using [11C]DASB [3-amino-4-(2 dimethylaminomethylphenylsulfanyl)-benzonitrile] positron emission tomography (PET) and plasma drug concentrations after the administration of escitalopram in 12 healthy volunteers. We then built a pharmacokinetic-pharmacodynamic model to characterize the dose-occupancy relationship in the putamen and the dorsal raphe nucleus. RESULTS: Escitalopram at approved doses occupied less SERT than expected and the SERT occupancy showed regional effects [occupancy was higher in the dorsal raphe nucleus than in the putamen (p < 0.001)]. The drug concentration when 50 % of receptors are occupied (EC50) value and Hill coefficient were significantly different between the putamen (EC50 4.30, Hill coefficient 0.459) and the dorsal raphe nucleus (EC50 2.89, Hill coefficient 0.817). CONCLUSIONS: Higher doses of escitalopram than 20 mg are needed to achieve 80 % or greater SERT occupancy. Higher occupancy by escitalopram in the dorsal raphe nucleus relative to the striatum may explain the delayed onset of action of SSRIs by modulating autoreceptor function. The prevention of the 5-HT1A autoreceptor mediated negative feedback could be a strategy for accelerating the clinical antidepressant effects. PMID- 27557551 TI - Does capitation payment under national health insurance affect subscribers' trust in their primary care provider? a cross-sectional survey of insurance subscribers in Ghana. AB - BACKGROUND: Ghana introduced capitation payment for primary care in 2012 with the view to containing escalating claims expenditure. This shift in provider payment method raised issues about its potential impact on patient-provider trust relationship and insured-patients' trust in the Ghana National Health Insurance Scheme. This paper presents findings of a study that explored insured-patients' perception about, and attitude towards capitation payment in Ghana; and determined whether capitation payment affect insured-patients' trust in their preferred primary care provider and the National Health Insurance Scheme in general. METHODS: We adopted a survey design for the study. We administered closed-ended questionnaires to collect data from insurance card-bearing members aged 18 years and above. We performed both descriptive statistics to determine proportions of observations relating to the variables of interest and chi-square test statistics to determine differences within gender and setting. RESULTS: Sixty-nine per cent (69 %) out of 344 of respondents selected hospital level of care as their primary care provider. The two most important motivations for the choice of a provider were proximity in terms of geographical access (40 %) and perceived quality of care (38 %). Eighty-eight per cent (88 %) rated their trust in their provider as (very) high. Eighty-two per cent (82 %) actively selected their providers. Eighty-eight per cent (88 %) had no intention to switch provider. A majority (91 %) would renew their membership when it expires. Female respondents (91 %; n = 281) were more likely to renew their membership than males (87 %; n = 63). Notwithstanding capitation payment experience, 81 % of respondents would recommend to their peers to enrol with the NHIS with rural dwellers (87 %; n = 156) being more likely to do so than urban dwellers (76 %; n = 188). Almost all respondents (92 %) rated the NHIS as (very) good. CONCLUSION: Health Insurance subscribers in Ghana have high trust in their primary care provider giving them quality care under capitation payment despite their negative attitude towards capitation payment. They are guided by proximity and quality of care considerations in their choice of provider. The NHIA would, however, have to address itself to the negative perceptions about the capitation payment policy. PMID- 27557552 TI - Optimizing stroke prevention in elderly patients with atrial fibrillation. PMID- 27557553 TI - Development of a multisystem surveillance database for transfusion-transmitted infections among blood donors in the United States. AB - BACKGROUND: The frequency of positive test results for transfusion-transmitted infections (TTIs) among blood donors is an important index of safety; thus, appropriate monitoring is critical, particularly when there are changes in policies affecting donor suitability. STUDY DESIGN AND METHODS: Testing algorithms from three large blood systems were reviewed and consensus definitions for a surveillance-positive result for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) established. In addition, information on each donation, including donor demographics and location, was collected. Combined data were analyzed to characterize the epidemiology of TTIs by person, place, and time. RESULTS: Data from 14.8 million donations were collected for 2011 to 2012, representing more than 50% of the US blood supply. Surveillance-positive rates per 10,000 donations were as follows: HBV, 0.76; HCV, 2.0; HIV, 0.28; and HTLV 0.34. Rates did not vary between the 2 years, although there was variation within a year. With the exception of HTLV, rates were higher among males, and all rates were higher among first-time donations. Window-period donations (those positive only in nucleic acid tests) were infrequent (HBV, 13; HCV, 60; HIV, 14) during the 2-year period. Frequencies of surveillance-positive results varied by donor age and residence location. CONCLUSIONS: We demonstrated that standardized data from multiple major US blood systems can be combined and analyzed for change. However, TTI frequencies are low, impacting their sensitivity to change. Furthermore, observed fluctuations in TTI frequencies may be secondary to changes in blood donor demographics rather than necessarily reflecting the immediate impact of policy modification. PMID- 27557554 TI - School lunches in the Republic of Ireland: a comparison of the nutritional quality of adolescents' lunches sourced from home or purchased at school or 'out' at local food outlets. AB - OBJECTIVE: To compare the energy, nutrient and food group compositions of three sources of school-day lunches among students in five secondary schools in the Republic of Ireland (ROI). DESIGN: Cross-sectional study conducted between October 2012 and March 2013. Students completed self-report food diaries over two school days. The energy, nutrient, nutrient density and food group composition of school-day lunches from home, school and 'out' in local food outlets were compared using ANCOVA and Tukey's Honest Significant Difference post hoc analysis. SETTING: Five secondary schools in the ROI. SUBJECTS: Male and female students aged 15-17 years (n 305). RESULTS: Six hundred and fifteen lunches (376 home lunches, 115 school lunches and 124 lunches sourced 'out' in the local environment) were analysed. School and 'out' purchased lunches were significantly higher than packed lunches from home in energy (2047 kJ (489 kcal), 2664 kJ (627 kcal), 1671 kJ (399 kcal), respectively), total fat (23.5 g, 30.1 g, 16.6 g, respectively) and free (added) sugars (12.6 g, 19.3 g, 7.4 g, respectively). More home lunches contained more fruit, wholemeal breads, cheese and red meat than lunches from school or 'out'. Meat products, chips and high-calorie beverages were sourced more frequently at school or 'out' than home. Fibre and micronutrient contents of lunches from all sources were low. CONCLUSIONS: Home sourced lunches had the healthiest nutritional profile in terms of energy and macronutrients. Foods high in energy, fat and free sugars associated with school and local food outlets are of concern given the public health focus to reduce their consumption. While school food should be improved, all sources of lunches need to be considered when addressing the dietary behaviours of secondary-school students. PMID- 27557555 TI - [Differences between adolescents with pathological Internet use in inpatient and outpatient treatment]. AB - Objective: In epidemiological studies high prevalence estimates for pathological Internet use in adolescence were reported. There are only few studies published, reporting data of adolescents seeking treatment concerning their pathological Internet use. Currently, a comparison of patients in inpatient versus outpatient treatment is not available. Method: We investigated 74 adolescents reporting pathological Internet use with standardized questionnaires concerning problematic Internet use, psychopathological symptoms and life satisfaction. Overall, 35 adolescents were treated in an outpatient and another 39 adolescents in an inpatient setting. Results: A substantial portion in both groups showed comorbid mental health problems. There were no differences in the degree of problematic Internet use between the two groups. However, compared to adolescents in an outpatient setting, adolescents in inpatient treatment reported longer average Internet usage times, a lower life satisfaction as well as more anxiety/depressiveness and self-esteem problems. In a multivariate logistic regression analysis Internet usage time and life satisfaction were identified as statistically significant factors for the affiliation to one of the two treatment groups. Conclusions: The results of the present study could be useful as a further description of this group of patients and more general to develop interventions for adolescents reporting pathological Internet use. PMID- 27557556 TI - Biochemical parameters of renal impairment/injury and surrogate markers of nephron number in intrauterine growth-restricted and preterm neonates at 30-40 days of postnatal corrected age. AB - BACKGROUND: Premature and/or intrauterine growth-restricted neonates have an increased risk of developing postnatal renal injuries in later life. Studies on renal physiology in these neonates at a corrected age of 30-40 days are scarce and mostly relate to preterm infants. The data from these studies often lack the results of correlation analyses between biochemical parameters and nephron number data which could provide additional insight and/or improve recognition of individuals at higher risk of renal failure. METHODS: Urinary total protein and albumin levels and N-acetyl-beta-D-glucosaminidase and cathepsin B activity were evaluated in preterm and intrauterine growth-restricted infants at a corrected age of 30-40 days and compared to data from a healthy control neonate population. The data were then associated with predominant susceptibility factors of renal damage related to low nephron number, such as gestational age, birth weight, total renal volume and renal cortex volume. RESULTS: Compared to the control neonate population, we found significantly increased levels of all biochemical parameters tested in the intrauterine growth-restricted neonates, whereas in the preterm infants we observed a significant increase in cathepsin B activity, total protein level and, to a lesser extent, albumin level. Cathepsin B activity showed a significant, strong and inverse correlation with all surrogate markers of nephron number and was also strongly and positively correlated with urinary albumin level. CONCLUSIONS: At this postnatal age, we found that lower nephron number in low birth weight neonates was associated to tubular impairment/injury that could be concurrent with a dysfunction of glomerular permeability. Urinary cathepsin B activity may be a candidate marker for the early prediction of renal susceptibility to damage in low birth weight neonates. PMID- 27557557 TI - Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort. AB - BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of >=0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN. PMID- 27557558 TI - Study of procaine and tetracaine in the lipid bilayer using molecular dynamics simulation. AB - Despite available experimental results, the molecular mechanism of action of local anesthetics upon the nervous system and contribution of the cell membrane to the process are still controversial. In this work, molecular dynamics simulations were performed to investigate the effect of two clinically used local anesthetics, procaine and tetracaine, on the structure and dynamics of a fully hydrated dimyristoylphosphatidylcholine lipid bilayer. We focused on comparing the main effects of uncharged and charged drugs on various properties of the lipid membrane: mass density distribution, diffusion coefficient, order parameter, radial distribution function, hydrogen bonding, electrostatic potential, headgroup angle, and water dipole orientation. To compare the diffusive nature of anesthetic through the lipid membrane quantitatively, we investigated the hexadecane/water partition coefficient using expanded ensemble simulation. We predicted the permeability coefficient of anesthetics in the following order: uncharged tetracaine > uncharged procaine > charged tetracaine > charged procaine. We also shown that the charged forms of drugs are more potent in hydrogen bonding, disturbing the lipid headgroups, changing the orientation of water dipoles, and increasing the headgroup electrostatic potential more than uncharged drugs, while the uncharged drugs make the lipid diffusion faster and increase the tail order parameter. The results of these simulation studies suggest that the different forms of anesthetics induce different structural modifications in the lipid bilayer, which provides new insights into their molecular mechanism. PMID- 27557560 TI - Erratum to: Use of signals and systems engineering to improve the safety of warfarin initiation. PMID- 27557559 TI - Epsin1 modulates synaptic vesicle retrieval capacity at CNS synapses. AB - Synaptic vesicle retrieval is an essential process for continuous maintenance of neural information flow after synaptic transmission. Epsin1, originally identified as an EPS15-interacting protein, is a major component of clathrin mediated endocytosis. However, the role of Epsin1 in synaptic vesicle endocytosis at CNS synapses remains elusive. Here, we showed significantly altered synaptic vesicle endocytosis in neurons transfected with shRNA targeting Epsin1 during/after neural activity. Endocytosis was effectively restored by introducing shRNA-insensitive Epsin1 into Epsin1-depleted neurons. Domain studies performed on neurons in which domain deletion mutants of Epsin1 were introduced after Epsin1 knockdown revealed that ENTH, CLAP, and NPFs are essential for synaptic vesicle endocytosis, whereas UIMs are not. Strikingly, the efficacy of the rate of synaptic vesicle retrieval (the "endocytic capacity") was significantly decreased in the absence of Epsin1. Thus, Epsin1 is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles. PMID- 27557562 TI - Performance of arsenene and antimonene double-gate MOSFETs from first principles. AB - In the race towards high-performance ultra-scaled devices, two-dimensional materials offer an alternative paradigm thanks to their atomic thickness suppressing short-channel effects. It is thus urgent to study the most promising candidates in realistic configurations, and here we present detailed multiscale simulations of field-effect transistors based on arsenene and antimonene monolayers as channels. The accuracy of first-principles approaches in describing electronic properties is combined with the efficiency of tight-binding Hamiltonians based on maximally localized Wannier functions to compute the transport properties of the devices. These simulations provide for the first time estimates on the upper limits for the electron and hole mobilities in the Takagi's approximation, including spin-orbit and multi-valley effects, and demonstrate that ultra-scaled devices in the sub-10-nm scale show a performance that is compliant with industry requirements. PMID- 27557561 TI - Simvastatin up-regulates adenosine deaminase and suppresses osteopontin expression in COPD patients through an IL-13-dependent mechanism. AB - BACKGROUND: Adenosine deaminase (ADA) and osteopontin (OPN) may play opposing roles in the pathogenesis of COPD. Deficiency of ADA results in enhanced adenosine signaling which up-regulates OPN expression. Although statins suppress OPN in cancer cells, little is known about their effects on ADA and OPN in COPD patients. METHODS: We extended a previous randomized double-blind placebo crossover study to investigate the effects of simvastatin (20 mg/day) on sputum ADA and OPN expression and explored the underlying signaling pathways involved by conducting in vitro experiments with cigarette smoke extract (CSE)-treated monocyte-derived macrophages (MDM) from COPD patients and healthy subjects. RESULTS: Simvastatin decreased sputum IL-13, OPN and CD73, while increasing ADA expression, irrespective of inhaled corticosteroid treatment and smoking status in parallel to increased inosine levels. The degree of simvastatin-restored ADA activity was significantly correlated with the magnitude of changes in pre bronchodilator FEV1. Mechanistic exploration showed that CSE enhanced the expression of IL-13, which induced an increase in OPN and inhibited ADA mRNA accumulation in MDM from COPD patients but not healthy subjects through a STAT6 dependent mechanism. Simvastatin treatment inhibited IL-13 transcription in a dose-dependent manner, and therefore diminished the IL-13-induced increase in OPN and restored IL-13-suppressed ADA. There was no effect of simvastatin on adenosine receptors in CSE-stimulated MDM, indicating that its effects were on the adenosine pathway. CONCLUSION: Simvastatin reversed IL-13-suppressed ADA activity that leads to the down-regulation of adenosine signaling and therefore inhibits OPN expression through the direct inhibition of IL-13-activated STAT6 pathway. Inhibition of IL-13 may reverse the imbalance between ADA and OPN in COPD and therefore may prevent COPD progression. PMID- 27557563 TI - Prediction of the originating site of sinonasal inverted papilloma by preoperative magnetic resonance imaging and computed tomography. AB - BACKGROUND: Precise localization and excision of the originating site of a sinonasal inverted papilloma (SNIP) is essential for decreasing tumor recurrence. In this study we evaluated the use of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) to pinpoint the attachment/originating sites of SNIPs in 143 patients. METHODS: Osteitis signs in CTs and convoluted cerebriform pattern (CCP)-based reverse tracings from MRIs of 143 SNIP patients were analyzed preoperatively to predict the originating site of SNIPs. The predicted sites were compared with actual SNIP attachment sites determined by surgery, and patients were followed-up for evaluation of SNIP recurrence rates over a mean period of about 4 years. RESULTS: Osteitis signs in CT accurately predicted the actual tumor attachment site in 49.7% of all patients. In comparison, convoluted cerebriform pattern (CCP)-based reverse tracings in MRI and combination CT plus MRI accurately predicted the SNIP originating sites in 84.1% and 86% of the patients, respectively. Sensitivity and specificity in predicting the SNIP originating site were: CT, 54.6% and 69.2%; MRI, 93.1% and 76.9%; and CT+MRI, 94.6% and 92.3%, respectively. A single postoperative recurrence occurred in 4.2% of the patients. CONCLUSIONS: Preoperative combination of MRI and CT provides a better option to accurately predict the SNIP originating site, and thus may facilitate accurate and complete excision of the SNIP. PMID- 27557564 TI - Association between mannose-binding lectin variants, haplotypes and risk of hepatocellular carcinoma: A case-control study. AB - The innate immunity gene mannose-binding lectin2 (MBL2) has played an important role in hepatitis B virus (HBV) infection, and the relationship between MBL2 variants and hepatocellular carcinoma (HCC) risk has not yet been identified. In total, 315 HCC cases and 315 healthy controls were enrolled and blood samples were acquired. High resolution melt analysis (HRM) was employed to genotype 6 polymorphisms in MBL2 gene. Increased HCC risk in carriers of LL genotype of -550 polymorphism with an adjusted OR (AOR) of 1.61 (95%CI = 1.00-2.57) was observed but no significant association detected in HL genotype. Both YX and XX genotype demonstrated a significantly elevated HCC risk in the analysis of -221 polymorphism. The B variants in codon 54 was also significantly associated with elevated HCC risk. HYB was identified as the protective factor of HCC while LXB was significantly associated with increase HCC risk. ELISA technique revealed that the MBL2 protein was significantly reduced in HCC cases. Moreover, both IL 1beta and IL-6 were inversely associated with plasma MBL2 level.The mutations in MBL2 could lead to compromised innate immunity, and possibly lead to elevated HCC risk, and a novel haplotype HXB has been identified with a rate of 12.5%. PMID- 27557565 TI - Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations. AB - Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. Mild TBI may lead to neuropsychiatric sequelae, including memory loss and motor impairment. Mitochondrial dysfunction and oxidative stress have a contributory role in several neurological disorders; however, their association with mitophagy in mild TBI is unclear. TBI was induced in female Sprague Dawley (SD) rats using a New York University Impactor (10 g, impactor head 2.5 mm diameter, weight drop 50 mm) and compared to sham surgery controls. The novel object recognition and error ladder tests were performed at 24 hours and for 6 weeks post injury, and the brains were examined histologically to confirm the extent of injury. Mitochondria manganese superoxide dismutase (MnSOD) and the oxidative phosphorylation (OXPHOS) complexes I-V (CI-CV), as well as mitophagy markers, dynamin related protein 1 (DRP-1), LC3A/B and PTEN-induced putative kinase 1 (PINK-1), were measured in the penumbra by western blot. At 24 hours sham rats performed as expected on a novel object recognition test while TBI rats showed cognitive deficits at the early time points. TBI rats also showed more early motor deficits on a horizontal ladder, compared with the sham rats. MnSOD, OXPHOS CI, CIII and CV protein levels were significantly lower in the TBI group at 24 hours. DRP-1, LC3A/B I and II, and PINK-1 were increased at 6 weeks suggesting abnormal mitophagy. Moderate TBI caused immediate cognitive and mild motor functional deficits in the rats that did not persist. Reduced antioxidative capacity and possibly compromised mitochondrial function may affect the long term functional recovery. PMID- 27557566 TI - Predicting complex syntactic structure in real time: Processing of negative sentences in Russian. AB - In Russian negative sentences the verb's direct object may appear either in the accusative case, which is licensed by the verb (as is common cross linguistically), or in the genitive case, which is licensed by the negation (Russian-specific "genitive-of-negation" phenomenon). Such sentences were used to investigate whether case marking is employed for anticipating syntactic structure, and whether lexical heads other than the verb can be predicted on the basis of a case-marked noun phrase. Experiment 1, a completion task, confirmed that genitive-of-negation is part of Russian speakers' active grammatical repertoire. In Experiments 2 and 3, the genitive/accusative case manipulation on the preverbal object led to shorter reading times at the negation and verb in the genitive versus accusative condition. Furthermore, Experiment 3 manipulated linear order of the direct object and the negated verb in order to distinguish whether the abovementioned facilitatory effect was predictive or integrative in nature, and concluded that the parser actively predicts a verb and (otherwise optional) negation on the basis of a preceding genitive-marked object. Similarly to a head-final language, case-marking information on preverbal noun phrases (NPs) is used by the parser to enable incremental structure building in a free word-order language such as Russian. PMID- 27557567 TI - Controlled Dealloying of Alloy Nanoparticles toward Optimization of Electrocatalysis on Spongy Metallic Nanoframes. AB - Atomic-level understanding of the structural transformations of multimetallic nanoparticles triggered by external stimuli is of vital importance to the enhancement of our capabilities to fine-tailor the key structural parameters and thereby to precisely tune the properties of the nanoparticles. Here, we show that, upon thermal annealing in a reducing atmosphere, Au@Cu2O core-shell nanoparticles transform into Au-Cu alloy nanoparticles with tunable compositional stoichiometries that are predetermined by the relative core and shell dimensions of their parental core-shell nanoparticle precursors. The Au-Cu alloy nanoparticles exhibit distinct dealloying behaviors that are dependent upon their Cu/Au stoichiometric ratios. For Au-Cu alloy nanoparticles with Cu atomic fractions above the parting limit, nanoporosity-evolving percolation dealloying occurs upon exposure of the alloy nanoparticles to appropriate chemical etchants, resulting in the formation of particulate spongy nanoframes with solid/void bicontinuous morphology composed of hierarchically interconnected nanoligaments. The nanoporosity evolution during percolation dealloying is synergistically guided by two intertwining structural rearrangement processes, ligament domain coarsening driven by thermodynamics and framework expansion driven by Kirkendall effects, both of which can be maneuvered by controlling the Cu leaching rates during the percolation dealloying. The dealloyed nanoframes possess large open surface areas accessible by the reactant molecules and high abundance of catalytically active undercoordinated atoms on the ligament surfaces, two unique structural features highly desirable for high-performance electrocatalysis. Using the room temperature electro-oxidation of methanol as a model reaction, we further demonstrate that, through controlled percolation dealloying of Au-Cu alloy nanoparticles, both the electrochemically active surface areas and the specific activity of the dealloyed metallic nanoframes can be systematically tuned to achieve the optimal electrocatalytic activities. PMID- 27557568 TI - Quick method for separating target compounds from the bark of Maqian (Zanthoxylum myriacanthum var. pubescens) by high-performance countercurrent chromatography. AB - Choosing a suitable solvent system for a countercurrent chromatography separation presents a challenge for many researchers. In this study, we introduce a quick method of separating a target compound from the bark of Zanthoxylum myriacanthum var. pubescens by countercurrent chromatography. This method relies on the thin layer chromatography based generally useful estimation of solvent systems. This paper will present how to quickly choose a suitable solvent system with a thin layer chromatography based generally useful estimation of solvent systems working chart. O-Methyltembamide (1) was enriched by countercurrent chromatography using n-hexane/ethyl acetate/methanol/water (6:4:6:4) as the solvent system. Further purification was achieved by high-performance liquid chromatography with purities of 98.2% from Z. myriacanthum var. pubescens bark. PMID- 27557569 TI - Histological Analysis of the Arabidopsis Gynoecium and Ovules Using Chloral Hydrate Clearing and Differential Interference Contrast Light Microscopy. AB - The use of chloral hydrate optical clearing paired with differential interference contrast microscopy allows the analysis of internal structures of developing plant organs without the need for paraffin embedding and sectioning. This approach is appropriate for the analysis of the developing gynoecium or seedpod of the flowering plant Arabidopsis thaliana and many other types of fixed plant material. Early stages of ovule development are observable with this approach. PMID- 27557570 TI - Indirect Immunofluorescence of Proteins in Oogenic Germ Cells of Caenorhabditis elegans. AB - Formation of full-grown oocytes requires the control and coordination of a number of processes (e.g., oocyte growth) through multiple stages, where disruption at any one step can result in infertility. Numerous proteins are required for the regulation and execution of the various oogenic processes as well as functioning as maternal products needed for embryogenesis. Immunofluorescence microscopy combined with staining using antibodies against specific proteins, or their posttranslationally modified forms, is a standard approach to determine the temporal and spatial location of gene products that function in oocyte development. The simple linear organization of the germline in the model organism Caenorhabditis elegans allows easy correlation of protein localization and germ cell developmental stage, thus aiding in our understanding of protein function during gametogenesis. Here we outline co-immunofluorescence staining for two major regulators of C. elegans germline development, the translational repressor GLD-1 and activated form of MPK-1 (dpMPK-1) ERK MAP kinase in dissected gonads from adult C. elegans. Worms are first dissected and the extruded gonads are fixed and permeabilized before being bathed in primary antibodies against GLD-1 and dpMPK-1. Secondary antibodies conjugated to fluorophore dyes and that target the IgG domains of the primary antibody reagents are then used to provide a fluorescent signal that corresponds to the position of GLD-1 and dpMPK-1. The outlined procedure is amenable to many other proteins expressed in C. elegans germ cells. PMID- 27557571 TI - Antibody Staining in Drosophila Germaria. AB - Drosophila oogenesis is a powerful model for studying a wide spectrum of cellular and developmental processes in vivo. Oogenesis starts in a specialized structure called the germarium, which harbors the stem cells for both germ and somatic cells. The germarium produces egg chambers, each of which will develop into an egg. Active areas of research in Drosophila germaria include stem cell self renewal, division, and maintenance, cell cycle control and differentiation, oocyte specification, intercellular communication, and signaling, among others. The solid knowledge base, the genetic tractability of the Drosophila model, as well as the availability and fast development of tools and imaging techniques for oogenesis research ensure that studies in this model will keep being instrumental for novel discoveries within cell and developmental biology also in the future. This chapter focuses on antibody staining in Drosophila germaria and provides a protocol for immunostaining as well as an overview of commonly used antibodies for visualization of different cell types and cellular structures. The protocol is well-suited for subsequent confocal microscopy analyses, and in addition we present key adaptations of the protocol that are useful when performing structured illumination microscopy (SIM) super-resolution imaging. PMID- 27557572 TI - In Vitro Culturing and Live Imaging of Drosophila Egg Chambers: A History and Adaptable Method. AB - The development of the Drosophila egg chamber encompasses a myriad of diverse germline and somatic events, and as such, the egg chamber has become a widely used and influential developmental model. Advantages of this system include physical accessibility, genetic tractability, and amenability to microscopy and live culturing, the last of which is the focus of this chapter. To provide adequate context, we summarize the structure of the Drosophila ovary and egg chamber, the morphogenetic events of oogenesis, the history of egg-chamber live culturing, and many of the important discoveries that this culturing has afforded. Subsequently, we discuss various culturing methods that have facilitated analyses of different stages of egg-chamber development and different types of cells within the egg chamber, and we present an optimized protocol for live culturing Drosophila egg chambers.We designed this protocol for culturing late-stage Drosophila egg chambers and live imaging epithelial tube morphogenesis, but with appropriate modifications, it can be used to culture egg chambers of any stage. The protocol employs a liquid-permeable, weighted "blanket" to gently hold egg chambers against the coverslip in a glass-bottomed culture dish so the egg chambers can be imaged on an inverted microscope. This setup provides a more buffered, stable, culturing environment than previously published methods by using a larger volume of culture media, but the setup is also compatible with small volumes. This chapter should aid researchers in their efforts to culture and live-image Drosophila egg chambers, further augmenting the impressive power of this model system. PMID- 27557573 TI - Using Fluorescent Reporters to Monitor Autophagy in the Female Germline Cells in Drosophila melanogaster. AB - Oogenesis is a fundamental biological process for the transmission of genetic information to the next generations. Drosophila has proven to be a valuable model for elucidating the molecular and cellular mechanisms involved in this developmental process. It has been shown that autophagy participates in the maturation of the egg chamber. Here we provide a protocol for monitoring and quantification of the autophagic process in the Drosophila germline cells using the fluorescent reporters mCherry-DmAtg8a and GFP-mCherry-DmAtg8a. PMID- 27557574 TI - Analysis of Phagocytosis in the Drosophila Ovary. AB - Programmed cell death (PCD) is essential for health and development. Generally, the last step of PCD is clearance, or engulfment, by phagocytes. Engulfment can be broken down into five basic steps: attraction of the phagocyte, recognition of the dying cell, internalization, phagosome maturation, and acidification of the engulfed material. The Drosophila melanogaster ovary serves as an excellent model to study diverse types of PCD and engulfment by epithelial cells. Here, we describe several methods to detect and analyze multiple steps of engulfment in the Drosophila ovary: recognition, vesicle uptake, phagosome maturation, and acidification. Annexin V detects phosphatidylserine, which is flipped to the outer leaflet of the plasma membrane of apoptotic cells, serving as an "eat me" signal. Several germline markers including tral-GFP, Orb, and cleaved Dcp-1 can all be used to label the germline and visualize its uptake into engulfing follicle cells. Drosophila strains expressing GFP and mCherry protein fusions can enable a detailed analysis of phagosome maturation. LysoTracker labels highly acidified compartments, marking phagolysosomes. Together these labels can be used to mark the progression of engulfment in Drosophila follicle cells. PMID- 27557575 TI - Immuno-Gold Labeling of Drosophila Follicles for Transmission Electron Microscopy. AB - Detecting the localization of cellular components using gold nanoparticles has come to offer tremendous advantages in cell biology, allowing for the high resolution imaging of the cellular organization at the subcellular level. This is further aided by the breakthroughs in the cryopreparation of samples, which focus at the retention of antigenicity in efforts to mirror the native state of the tissues and cells as closely as possible. Herein, we describe the methodology for immuno-gold labeling of Drosophila follicles, following preparation of the samples using the Tokuyasu method for ultracryosectioning. PMID- 27557576 TI - Preparation of Drosophila Follicles for Transmission Electron Microscopy. AB - Transmission Electron Microscopy (TEM) provides high resolution and accuracy at the subcellular level for observing and investigating cellular structures. This is essential for understanding a large variety of cellular processes. In this chapter, we describe a detailed protocol for preparing Drosophila follicles in order to be used as a specimen for transmission electron microscopy. PMID- 27557577 TI - Quantitative Real-Time PCR Analysis of Gene Transcripts of Mosquito Follicles. AB - Real-time (quantitative) PCR, or QPCR, has become an indispensible tool for characterizing gene expression. Depending on the experimental design, researchers can use either the relative or absolute (standard curve) method to quantify transcript abundance. Characterizing the expression of genes in mosquito ovaries will require use of the standard curve method of quantification. Here, I describe reagents and equipment necessary to run standard curve QPCR. I also provide details on the construction of the standard linear curve and calculations required to determine transcript abundance. PMID- 27557578 TI - Studying Oogenesis in a Non-model Organism Using Transcriptomics: Assembling, Annotating, and Analyzing Your Data. AB - This chapter provides a guide to processing and analyzing RNA-Seq data in a non model organism. This approach was implemented for studying oogenesis in the Speckled Wood Butterfly Pararge aegeria. We focus in particular on how to perform a more informative primary annotation of your non-model organism by implementing our multi-BLAST annotation strategy. We also provide a general guide to other essential steps in the next-generation sequencing analysis workflow. Before undertaking these methods, we recommend you familiarize yourself with command line usage and fundamental concepts of database handling. Most of the operations in the primary annotation pipeline can be performed in Galaxy (or equivalent standalone versions of the tools) and through the use of common database operations (e.g. to remove duplicates) but other equivalent programs and/or custom scripts can be implemented for further automation. PMID- 27557579 TI - Live Imaging of Centriole Dynamics by Fluorescently Tagged Proteins in Starfish Oocyte Meiosis. AB - High throughput DNA sequencing, the decreasing costs of DNA synthesis, and universal techniques for genetic manipulation have made it much easier and quicker to establish molecular tools for any organism than it has been 5 years ago. This opens a great opportunity for reviving "nonconventional" model organisms, which are particularly suited to study a specific biological process and many of which have already been established before the era of molecular biology. By taking advantage of transcriptomics, in particular, these systems can now be easily turned into full fetched models for molecular cell biology.As an example, here we describe how we established molecular tools in the starfish Patiria miniata, which has been a popular model for cell and developmental biology due to the synchronous and rapid development, transparency, and easy handling of oocytes, eggs, and embryos. Here, we detail how we used a de novo assembled transcriptome to produce molecular markers and established conditions for live imaging to investigate the molecular mechanisms underlying centriole elimination-a poorly understood process essential for sexual reproduction of animal species. PMID- 27557580 TI - High-Pressure Freezing Electron Microscopy of Zebrafish Oocytes. AB - Oogenesis is an essential cellular and developmental process to prepare the oocyte for propagation of a species after fertilization. Oocytes of oviparous animals are enormous cells endowed with many, big cellular compartments, which are interconnected through active intracellular transport. The dynamic transport pathways and the big organelles of the oocyte provide the opportunity to study cellular trafficking with outstanding resolution. Hence, oocytes were classically used to investigate cellular compartments. Though many novel regulators of vesicle trafficking have been discovered in yeast, tissue culture cells and invertebrates, recent forward genetic screens in invertebrate and vertebrate oocytes isolated novel control proteins specific to multicellular organisms. Zebrafish is a widely used vertebrate model to study cellular and developmental processes in an entire animal. The transparency of zebrafish embryos allows following cellular events during early development with in vivo imaging. Unfortunately, the active endocytosis of the oocyte also represents a drawback for imaging. The massive amounts of yolk globules prevent the penetration of light-beams and currently make in vivo microscopy a challenge. As a consequence, electron microscopy (EM) still provides the highest resolution to analyze the ultra-structural details of compartments and organelles and the mechanisms controlling many cellular pathways of the oocyte. Among different fixation approaches for EM, High Pressure Freezing (HPF) in combination with freeze substitution significantly improves the samples preservation closest to their natural status. Here, we describe the HPF with freeze substitution embedding method for analyzing cellular processes in zebrafish oocytes using electron microscopy. PMID- 27557581 TI - Cytoskeleton and Cytoskeleton-Bound RNA Visualization in Frog and Insect Oocytes. AB - The majority of oocyte functions involves and depends on the cytoskeletal elements, which include microtubules and actin and cytokeratin filaments. Various structures and molecules are temporarily or permanently bound to the cytoskeletal elements and their functions rely on cytoskeleton integrity and its timely assembly. Thus the accurate visualization of cytoskeleton is often crucial for studies and analyses of oocyte structure and functions. Here we describe several reliable methods for microtubule and/or microfilaments preservation and visualization in Xenopus oocyte extracts, and in situ in live and fixed insect and frog (Xenopus) oocytes. In addition, we describe visualization of cytoskeleton-bound RNAs using molecular beacons in live Xenopus oocytes. PMID- 27557582 TI - RNA FISH, DNA FISH and Chromosome Painting of Chicken Oocytes. AB - Fluorescence in situ hybridization (FISH) is a molecular cytogenetic technique. It identifies the location of DNA loci and RNAs, including nascent RNAs in the process of being transcribed, within individual cells. Great advances in fluorescent dye technology and technique sensitivity, combined with developments in light microscopy and imaging software have made it widely accessible and have expanded the range of applications in basic research as well as in diagnostics. Being able to perform RNA hybridization, DNA hybridization, and protein immunofluorescence consecutively on the same sample is an invaluable tool to study RNA expression in relation to their gene loci and to map RNA and DNA in relation to nuclear or cellular structures. This has contributed to enormous progress in understanding basal mechanisms of male and female meiosis in different animal model systems. In this chapter we describe in detail the protocols for FISH based techniques applied to study gene expression dynamics and nuclear architecture of chicken oocytes during meiotic prophase I. These techniques can be easily performed in any molecular and cell biology laboratory and be adapted to different systems and to different phases of gametogenesis. PMID- 27557583 TI - Preparation of Cell Lysate from Mouse Oocytes for Western Blotting Analysis. AB - Western Blotting has been used extensively for the identification of the protein factors that regulate mammalian oocyte meiosis. However, the limitations in collecting sufficient numbers of oocytes can hinder the efficiency of the technique. Here we provide a detailed protocol for the accurate preparation of mouse oocyte samples for Western Blotting analysis. PMID- 27557584 TI - Quantitative Microinjection of Morpholino Antisense Oligonucleotides into Mouse Oocytes to Examine Gene Function in Meiosis-I. AB - Specific protein depletion is a powerful approach for assessing individual gene function in cellular processes, and has been extensively employed in recent years in mammalian oocyte meiosis-I. Conditional knockout mice and RNA interference (RNAi) methods such as siRNA or dsRNA microinjection are among several approaches to have been applied in this system over the past decade. RNAi by microinjection of Morpholino antisense Oligonucleotides (MO), in particular, has proven highly popular and tractable in many studies, since MOs have high specificity of interaction, low cell toxicity, and are more stable than other microinjected RNAi molecules. Here, we describe a method of MO microinjection into the mouse germinal vesicle-stage (GV) oocyte followed by a simple immunofluorescence approach for examination of gene function in meiosis-I. PMID- 27557585 TI - Monitoring Calcium Oscillations in Fertilized Mouse Eggs. AB - In mammalian species, including human, fertilization is characterized by the triggering of long-lasting calcium (Ca(2+)) oscillations in the egg cytoplasm. The monitoring of these Ca(2+) oscillations is a valuable technique to demonstrate that fertilization has occurred, to study egg activation events elicited downstream of the Ca(2+) signal, as well as to evaluate sperm quality. This chapter describes our protocol to monitor sperm-induced Ca(2+) oscillations in mouse eggs, using fluorescence microscopy techniques and the Fura-2-AM ratiometric Ca(2+) indicator. PMID- 27557586 TI - Live Imaging of Intracellular Dynamics During Meiotic Maturation in Mouse Oocytes. AB - Fluorescence live imaging is a powerful approach to study intracellular dynamics during cellular events such as cell division. By applying automated confocal live imaging to mouse oocytes, in which meiotic maturation can be induced in vitro after the introduction of fluorescent proteins through microinjection, the meiotic dynamics of intracellular structures, such as chromosomes, can be monitored at high resolution. A combination of this method with approaches for the perturbation of specific proteins opens up opportunities for understanding the molecular and intracellular basis of mammalian meiosis. PMID- 27557587 TI - Isolation of Mammalian Oogonial Stem Cells by Antibody-Based Fluorescence Activated Cell Sorting. AB - The ability to isolate and subsequently culture mitotically active female germ cells from adult ovaries, referred to as either oogonial stem cells (OSCs) or adult female germline stem cells (aFGSCs), has provided a robust system to study female germ cell development under multiple experimental conditions, and in many species. Flow cytometry or fluorescence-activated cell sorting (FACS) is an integral part of many isolation and characterization protocols. Here, we provide methodological details for antibody-based flow cytometric isolation of OSCs using antibodies specific for external epitopes of the proteins Ddx4 or Ifitm3, alone or in combination with the use of fluorescent reporter mice. Beginning with sample preparation, we provide point-by-point instructions to guide researchers on how to isolate OSCs using flow cytometry. PMID- 27557588 TI - Immunohistochemistry of Paraffin Sections from Mouse Ovaries. AB - Immunohistochemistry (IHC) is an efficient technique to detect cellular localizations of the proteins in paraffin-embedded tissues. It allows specific proteins to be visualized by the interaction of antibodies with an enzyme substrate-chromogen system. Here, we describe indirect immunohistochemistry method for paraffin-embedded mouse ovaries fixed with Bouin's Fixative. PMID- 27557589 TI - Jessner's solution vs. 30% salicylic acid peels: a comparative study of the efficacy and safety in mild-to-moderate acne vulgaris. AB - INTRODUCTION: Chemical peeling is a well-identified therapeutic modality for acne vulgaris (AV). Jessner's solution (JS) is a known peeling agent for acne since more than 100 years. Salicylic acid (SA) peel is a well-established peeling agent for acne. There is paucity of literature comparing the current peeling agents of choice, that is, SA with the older peeling agents, that is, JS for acne. OBJECTIVE: To compare the efficacy and safety of 30% SA vs. JS peels in treatment of mild-to-moderate facial acne in Indian patients. MATERIALS AND METHOD: A total of 40 patients with mild-to-moderate AV were enrolled for 12 weeks and were randomly divided into two groups: group 1, 30% SA peels and group 2, JS peels were performed 2 weeks apart with total of six peels in 12-week duration. Clinical improvement was assessed objectively using Michaelsson acne scores (MAS) and clinical photographs. Side effects were observed at each visit. RESULTS: At the end of therapy, improvement in MAS and percentage decrease in MAS were significantly higher in group 1 as compared to group 2. Likewise, decrease in mean comedone counts in group 1 was significantly higher as compared to group 2. However, there was no statistically significant difference in the decrease in mean papule and pustule counts between the two groups. Both the groups tolerated the peels well. CONCLUSION: Thus, 30% SA peels were more effective than JS peels in treatment of noninflammatory lesions, that is, comedones and in overall improvement of mild-to-moderate facial acne vulgaris. PMID- 27557590 TI - The contributions to long-term health-relevant particulate matter at the UK EMEP supersites between 2010 and 2013: Quantifying the mitigation challenge. AB - Human health burdens associated with long-term exposure to particulate matter (PM) are substantial. The metrics currently recommended by the World Health Organization for quantification of long-term health-relevant PM are the annual average PM10 and PM2.5 mass concentrations, with no low concentration threshold. However, within an annual average, there is substantial variation in the composition of PM associated with different sources. To inform effective mitigation strategies, therefore, it is necessary to quantify the conditions that contribute to annual average PM10 and PM2.5 (rather than just short-term episodic concentrations). PM10, PM2.5, and speciated water-soluble inorganic, carbonaceous, heavy metal and polycyclic aromatic hydrocarbon components are concurrently measured at the two UK European Monitoring and Evaluation Programme (EMEP) 'supersites' at Harwell (SE England) and Auchencorth Moss (SE Scotland). In this work, statistical analyses of these measurements are integrated with air mass back trajectory data to characterise the 'chemical climate' associated with the long-term health-relevant PM metrics at these sites. Specifically, the contributions from different PM concentrations, months, components and geographic regions are detailed. The analyses at these sites provide policy-relevant conclusions on mitigation of (i) long-term health-relevant PM in the spatial domain for which these sites are representative, and (ii) the contribution of regional background PM to long-term health-relevant PM. At Harwell the mean (+/-1 sd) 2010-2013 annual average concentrations were PM10=16.4+/-1.4MUgm(-3) and PM2.5=11.9+/-1.1MUgm(-3) and at Auchencorth PM10=7.4+/-0.4MUgm(-3) and PM2.5=4.1+/-0.2MUgm(-3). The chemical climate state at each site showed that frequent, moderate hourly PM10 and PM2.5 concentrations (defined as approximately 5-15MUgm(-3) for PM10 and PM2.5 at Harwell and 5-10MUgm(-3) for PM10 at Auchencorth) determined the magnitude of annual average PM10 and PM2.5 to a greater extent than the relatively infrequent high, episodic PM10 and PM2.5 concentrations. These moderate PM10 and PM2.5 concentrations were derived across the range of chemical components, seasons and air-mass pathways, in contrast to the highest PM concentrations which tended to associate with specific conditions. For example, the largest contribution to moderate PM10 and PM2.5 concentrations - the secondary inorganic aerosol components, specifically NO3(-) - were accumulated during the arrival of trajectories traversing the spectrum of marine, UK, and continental Europe areas. Mitigation of the long-term health-relevant PM impact in the regions characterised by these two sites requires multilateral action, across species (and hence source sectors), both nationally and internationally; there is no dominant determinant of the long-term PM metrics to target. PMID- 27557591 TI - Adherence to the Mediterranean diet is inversely associated with metabolic syndrome occurrence: a meta-analysis of observational studies. AB - Diet plays a role in the onset and progression of metabolic disorders, including metabolic syndrome (MetS). We aimed to systematically review and conduct a quantitative meta-analysis of results from observational cross-sectional and prospective cohort studies on adherence to the Mediterranean dietary pattern and risk of MetS. Literature databases including PubMed, SCOPUS and EMBASE were searched from the beginning to May 2016. Eight cross-sectional and four prospective studies were included in this meta-analysis, accounting for a total of 33,847 individuals and 6342 cases of MetS. High adherence to the Mediterranean diet was associated with a risk of MetS (RR: 0.81, 95%CI: 0.71, 0.92). Regarding individual components of the MetS, the inverse associations were significant for waist circumference, blood pressure and low HDL-C levels. In conclusion, adoption of a Mediterranean dietary pattern was associated with lower risk of the MetS and it can be proposed for the primary prevention of the MetS. PMID- 27557592 TI - Experiment and simulation of novel liquid crystal plasma mirrors for high contrast, intense laser pulses. AB - We describe the first demonstration of plasma mirrors made using freely suspended, ultra-thin films formed dynamically and in-situ. We also present novel particle-in-cell simulations that for the first time incorporate multiphoton ionization and dielectric models that are necessary for describing plasma mirrors. Dielectric plasma mirrors are a crucial component for high intensity laser applications such as ion acceleration and solid target high harmonic generation because they greatly improve pulse contrast. We use the liquid crystal 8CB and introduce an innovative dynamic film formation device that can tune the film thickness so that it acts as its own antireflection coating. Films can be formed at a prolonged, high repetition rate without the need for subsequent realignment. High intensity reflectance above 75% and low-field reflectance below 0.2% are demonstrated, as well as initial ion acceleration experimental results that demonstrate increased ion energy and yield on shots cleaned with these plasma mirrors. PMID- 27557593 TI - Osmoregulation in Saccharomyces cerevisiae via mechanisms other than the high osmolarity glycerol pathway. AB - The response of Saccharomyces cerevisiae to osmotic stress, whether arising from environmental conditions or physiological processes, has been intensively studied in the last two decades. The well-known high-osmolarity glycerol (HOG) signalling pathway that is induced in response to osmotic stress interacts with other signalling pathways such as the cell wall integrity and the target of rapamycin pathways. Osmotic balance is also maintained by the regulated opening and closing of channel proteins in both the cell membrane and intracellular organelles such as the vacuole. Additionally, environmental stresses, including osmotic shock, induce intracellular calcium signalling. Thus, adaptation to environmental stresses in general, and osmotic stress in particular, is dependent on the concerted action of components of multiple interacting pathways. In this review, we describe some of the major mechanisms and molecules involved in osmoregulation via pathways other than the high-osmolarity glycerol pathway and their known interactions with one another that have been discovered over the last two decades. PMID- 27557594 TI - Identification and inhibition of carbonic anhydrases from nematodes. AB - Carbonic anhydrases (CAs) are metalloenzymes, and classified into the evolutionarily distinct alpha, beta, gamma, delta, zeta, and eta classes. alpha CAs are present in many living organisms. beta- and gamma-CAs are expressed in most prokaryotes and eukaryotes, except for vertebrates. delta- and zeta-CAs are present in phytoplanktons, and eta-CAs have been found in Plasmodium spp. Since the identification of alpha- and beta-CAs in Caenorhabditis elegans, the nematode CAs have been considered as an emerging target in research focused on antiparasitic CA inhibitors. Despite the presence of alpha-CAs in both helminths and vertebrates, structural studies have revealed different kinetic and inhibition results. Moreover, lack of beta-CAs in vertebrates makes this enzyme as an attractive target for inhibitory studies against helminthic infection. Some CA inhibitors, such as sulfonamides, have been evaluated against nematode CAs. This review article aims to present comprehensive information about the nematode CAs and their inhibitors as potential anthelminthic drugs. PMID- 27557595 TI - Reagents with a Crystalline Coat. AB - Tetrakis(dimethoxyphenyl)adamantane (TDA) readily forms crystalline inclusion complexes with reactive, toxic, or malodorous reagents, such as benzoyl chloride, acetyl chloride, cyclohexyl isocyanide, phosphorus trichloride, and trimethylsilyl chloride. The crystals are stable and largely free of the problematic properties of the free reagents. When exposed to solvents such as DMSO or MeOH, the reagents react, and a large portion of the TDA precipitates. The TDA-coated reagents may lead to a safer way of storing, handling, and delivering reagents, and ultimately to synthetic protocols that do not require fume hoods. PMID- 27557597 TI - Global dermatology: challenges and changes? PMID- 27557598 TI - Reed's syndrome, a diagnosis not to forget. PMID- 27557596 TI - Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation. AB - Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body's iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen. This results in iron-limited erythropoiesis and anemia. This review summarizes current diagnostic and pathophysiological concepts of iron deficiency anemia and anemia of inflammation, as well as combined conditions, and provides a brief outlook on novel therapeutic options. PMID- 27557599 TI - A man with abdominal pain and skin pigmentation. PMID- 27557600 TI - The old open question of marijuana and healthcare: Flares from NANHES. PMID- 27557601 TI - Environmental Contamination by Heavy Metals in Region with Previous Mining Activity. AB - Due to its status as one of the most contaminated regions in Slovakia, 45 soil and plant samples were collected in the Middle Spis region. In soil, the exchangeable soil reaction, humus content and heavy metals content (Zn, Cd, Cu, Pb, Hg) were determined. Total content of heavy metals (TC-HMs) and content of mobile forms (MF-HMs) in soil, as well as metal content in plants, were determined by atomic absorption spectrometry. The concentration ranges for total Zn, Cd, Cu, Pb and Hg in soil were 33.1-953, 0.65-6.73, 11.0-913, 26.5-165 and 0.28--415 mg/kg, respectively. The overall concentration ranges of these metals in plants of two types (Athyrium filix-femina L. and Poaceae herbs) were 12.4 158.6, 0.10-1.63, 3.34-85.7, 0.09-29.7 and 0.01-12.8 mg/kg, respectively. Despite the values of Zn, Cd, Cu, Pb and Hg content in the soil exceeding limit values, only the Hg content in plants presented an ecological risk. PMID- 27557602 TI - Influence of Formulation on Mobility of Clomazone in Soil. AB - The mobility of clomazone [2-(2-chlorobenzylo)-4,4-dimetylo-1,2-oxazolidin-3-one] in a loamy sand soil and a sand soil was studied in a soil column under laboratory conditions. Commercial clomazone formulation (Command 480 EC) and clomazone immobilized in an alginate matrix were used for a leaching experiment. For both formulations, the same dose of 2.0 mg of the active substance was applied. After an application of a herbicide, the columns were irrigated with: 100, 40 and 3.7 mm of water. After 1 h, when an addition of water was completed, the soils were sampled in the 5 cm segments and were used for the analysis of the residues. The use of an alginate formulation reduced the vertical mobility of clomazone into a soil layer in comparison with the formulation EC. PMID- 27557606 TI - Multicentre observational study of surgical system failures in aortic procedures and their effect on patient outcomes. AB - BACKGROUND: Vascular surgical care has changed dramatically in recent years with little knowledge of the impact of system failures on patient safety. The primary aim of this multicentre observational study was to define the landscape of surgical system failures, errors and inefficiency (collectively termed failures) in aortic surgery. Secondary aims were to investigate determinants of these failures and their relationship with patient outcomes. METHODS: Twenty vascular teams at ten English hospitals trained in structured self-reporting of intraoperative failures (phase I). Failures occurring in open and endovascular aortic procedures were reported in phase II. Failure details (category, delay, consequence), demographic information (patient, procedure, team experience) and outcomes were reported. RESULTS: There were strong correlations between the trainer and teams for the number and type of failures recorded during 88 procedures in phase I. In 185 aortic procedures, teams reported a median of 3 (i.q.r. 2-6) failures per procedure. Most frequent failures related to equipment (unavailability, failure, configuration, desterilization). Most major failures related to communication. Fourteen failures directly harmed 12 patients. Significant predictors of an increased failure rate were: endovascular compared with open repair (incidence rate ratio (IRR) for open repair 0.71, 95 per cent c.i. 0.57 to 0.88; P = 0.002), thoracic aneurysms compared with other aortic pathologies (IRR 2.07, 1.39 to 3.08; P < 0.001) and unfamiliarity with equipment (IRR 1.52, 1.20 to 1.91; P < 0.001). The major failure total was associated with reoperation (P = 0.011), major complications (P = 0.029) and death (P = 0.027). CONCLUSION: Failure in aortic procedures is frequently caused by issues with team working and equipment, and is associated with patient harm. Multidisciplinary team training, effective use of technology and new-device accreditation may improve patient outcomes. PMID- 27557607 TI - Effect of Wild and Cultivated Rice Genotypes on Rhizosphere Bacterial Community Composition. AB - BACKGROUND: Deposition and secretion from roots influences the composition of the microbial communities surrounding them in the rhizosphere, and microbial activities influence the growth and health of the plant. Different host plant genotypes result in differences in those microbial communities. Crop genomes may have a narrow genetic base because of bottlenecks that occurred when domesticated crops were derived from small populations within the progenitor species. Desirable traits influencing root-associated microbial communities might therefore have been lost in the transition from wild species to modern cultivars. To investigate the diversity of bacterial communities associated with wild and cultivated rice, we surveyed a series of plant species and cultivars spanning the Oryza genus, growing them in the same nutrient-poor soil and assessing the bacterial composition of their rhizospheres and the surrounding soil using 16S rDNA sequencing. RESULTS: Root-associated bacterial communities showed small but significant differences dependent on the plant genotype. We found that differences between bacteria associated with differing plant genotypes were only weakly correlated with the phylogenetic distance between the Oryza wild species and cultivars. In ordination plots, domesticated and wild samples could be separated on the basis of their associated bacterial communities. Taxa of the Anaerolineae were overrepresented in wild samples compared to domesticated ones. Certain methanotrophs were overrepresented in the earliest diverged part of the Oryza genus. CONCLUSIONS: Bacterial populations associated with the rhizosphere of wild rice species displayed differences with those associated with cultivars, suggesting that root traits selected in domestication could have significant influence on the rhizosphere microbiota composition. Variation within the genus seems to influence the representation of methanotrophs. This suggests that greenhouse emissions from paddy fields could be altered by manipulating plant genotypes through the introgression of wild rice genetic material. PMID- 27557608 TI - Sulfatides in extracellular vesicles isolated from plasma of multiple sclerosis patients. AB - Extracellular vesicles (EVs) are membrane nanovesicles of diverse sizes secreted by different cell types and are involved in intercellular communication. EVs shuttle proteins, nucleic acids, and lipids that reflect their cellular origin and could mediate their biological function in recipient cells. EVs circulate in biological fluids and are considered as potential biomarkers that could be used to analyze and characterize disease development, course and response to treatment. EVs exhibit specific distribution of glycolipids and membrane organization, but little is known about the biological significance of this distribution or how it could contribute to pathological conditions such as multiple sclerosis (MS). We provide the first description of sulfatide composition in plasma-derived EVs by ultra-high-performance liquid chromatography tandem mass spectrometry. We found that EVs of different sizes showed C16:0 sulfatide but no detectable levels of C18:0, C24:0, or C24:1 sulfatide species. Small EVs isolated at 100,000 * g-enriched in exosomes-from plasma of patients with MS showed a significant increase of C16:0 sulfatide compared with healthy controls. Nanoparticle tracking analysis showed that the particle size distribution in MS plasma was significantly different compared with healthy controls. Characterization of small EVs isolated from MS plasma showed similar protein content and similar levels of exosomal markers (Alix, Rab-5B) and vesicular marker MHC class I (major histocompatibility complex class I) compared with healthy controls. Our findings indicate that C16:0 sulfatide associated with small EVs is a candidate biomarker for MS that could potentially reflect pathological changes associated with this disease and/or the effects of its treatment. (c) 2016 Wiley Periodicals, Inc. PMID- 27557609 TI - Satisfaction assessment with malleable prosthetic implant of Spectra (AMS) and Genesis (Coloplast) models. AB - The malleable prosthetic implant is widely accepted among patients and physicians owing to a lower degree of surgical complexity, its rare mechanic failures and lower cost. We have compared the degree of satisfaction with malleable prosthetic implant in 60 patients, 36 with Spectra (AMS) and 24 with Genesis (Coloplast). For assessment purposes, we implemented the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) satisfaction questionnaire adapted for penile prosthetic implants. The mean age and follow-up was 61.7 years (31-82) and 19.9 months (1-61), respectively. Mean EDITS scores did not indicate superiority of one implant over the other, overall satisfaction index being 77.1% and 75.6% for Genesis and Spectra prosthesis, respectively (P=0.4970). Our results revealed that these two models of malleable prostheses present a high level of satisfaction and confirm that the malleable prosthetic implant is an excellent option to treat patients with ED refractory to medical treatment. PMID- 27557610 TI - Event-level impact of Promescent on quality of sexual experience in men with subjective premature ejaculation. AB - Promescent is a lidocaine-based ejaculation delaying spray that absorbs into the skin of the penis prior to sexual activity. This article aimed to evaluate the effect of Promescent on the experience of orgasm, ejaculatory latency time and quality of sexual experience (QSE). Additionally, we assessed ease of application of Promescent and the extent to which it enhanced or interrupted the sexual experience. The analytic sample consisted of 91 men with self-reported subjective premature ejaculation who were sent a sample of Promescent and completed a 14-day internet-based prospective daily electronic report. Average ejaculatory latency time was 11.16 min during product use events, compared with 6.81 min during product non-use events. Both members of the couple had an orgasm 65.6% of the time when they used the product, compared with 44.1% when they did not use the product. QSE was significantly improved on product use days (P<0.05). Quality also significantly improved each subsequent time the product was used (P<0.01). The product was reported as easy to use and did not interrupt the sexual experience. Findings suggest that the use of this topical spray significantly improves QSE and perception of partner experience, and that these improve with longer duration of use. PMID- 27557611 TI - Anti-inflammatory and anti-fibrotic effects of annexin1 on erectile function after cavernous nerve injury in rats. AB - The aim of this study was to investigate the effect of the anti-inflammatory and anti-fibrotic actions of ANX1 on erectile function (EF). Forty-eight male Wistar rats were randomly distributed into four equal groups: one group (sham operation control) and three groups (bilateral cavernous nerve (CN) crush injury). Crush injury groups were treated prior to injury with an intravascular injection of either ANX1 (50 or 100 MUg kg-1) or vehicle. EF was assessed by CN electrical stimulation at 2 and 7 days after CN injury with histomorphometric and immunohistochemical analysis. ANX1 demonstrated functional preservation as the increase in intracavernous pressure (ICP). A dose-response relationship regarding the effect on penile tissue was confirmed, and preservation of the penile dorsal nerves and anti-apoptotic effects in the corpus cavernosum (real P-value vs injured control). ANX1 treatment prevented collagen deposition and smooth muscle loss in the penis. ANX1 normalized the expression of vascular endothelial growth factor and decreased tumor necrosis factor-alpha in the lumen of the blood vessels of the organ. ANX1 proved effective in preserving EF in a rat model of neurogenic erectile dysfunction. ANX1 treatment before CN injury in rats improved erectile recovery, enhanced vascular regeneration and preserved the micro architecture of the corpus cavernosum. The clinical availability of this compound merits application in penile rehabilitation studies following radical prostatectomy. PMID- 27557612 TI - Joule heating effects on electroosmotic entry flow. AB - Electroosmotic flow is the transport method of choice in microfluidic devices over traditional pressure-driven flow. To date, however, studies on electroosmotic flow have been almost entirely limited to inside microchannels. This work presents the first experimental study of Joule heating effects on electroosmotic fluid entry from the inlet reservoir (i.e., the well that supplies fluids and samples) to the microchannel in a polymer-based microfluidic chip. Electrothermal fluid circulations are observed at the reservoir-microchannel junction, which grow in size and strength with the increasing alternating current to direct current voltage ratio. Moreover, a 2D depth-averaged numerical model is developed to understand the effects of Joule heating on fluid temperature and flow fields in electrokinetic microfluidic chips. This model overcomes the problems encountered in previous unrealistic 2D and costly 3D models, and is able to predict the observed electroosmotic entry flow patterns with a good agreement. PMID- 27557613 TI - Recent advances in engineering propionyl-CoA metabolism for microbial production of value-added chemicals and biofuels. AB - Diminishing fossil fuel reserves and mounting environmental concerns associated with petrochemical manufacturing practices have generated significant interests in developing whole-cell biocatalytic systems for the production of value-added chemicals and biofuels. Although acetyl-CoA is a common natural biogenic precursor for the biosynthesis of numerous metabolites, propionyl-CoA is unpopular and non-native to most organisms. Nevertheless, with its C3-acyl moiety as a discrete building block, propionyl-CoA can serve as another key biogenic precursor to several biological products of industrial importance. As a result, engineering propionyl-CoA metabolism, particularly in genetically tractable hosts with the use of inexpensive feedstocks, has paved an avenue for novel biomanufacturing. Herein, we present a systematic review on manipulation of propionyl-CoA metabolism as well as relevant genetic and metabolic engineering strategies for microbial production of value-added chemicals and biofuels, including odd-chain alcohols and organic acids, bio(co)polymers and polyketides. [Formula: see text]. PMID- 27557614 TI - One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation. AB - A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications. PMID- 27557615 TI - Effect of Kineret(r) on ovarian ischemia reperfusion injury in a rat model. AB - AIM: To investigate the effect of Kineret(r) on ischemia reperfusion (IR) injury in rat ovaries. METHODS: Rats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret(r) + ovarian IR (KIR-50); 100 mg/kg Kineret(r) + ovarian IR (KIR 100); and sham operation (SOC). KIR-50 (n = 10) and KIR-100 (n = 10) groups received an intraperitoneal injection of Kineret(r) at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method. The results were compared between the groups. RESULTS: In rats in which IR occurred, oxidant parameters, such as malondialdehyde (MDA) and myeloperoxidase (MPO), were increased, the level of proinflammatory interleukin 1 beta (IL-1beta) was elevated and total glutathione (tGSH) as an antioxidant was decreased in the ovarian tissues. Administration of Kineret(r) at a dose of 100 mg/kg inhibited the increase of MDA, MOP and IL-1beta and a decrease in tGSH caused by IR more significantly than administration of Kineret(r) at a dose of 50 mg/kg. In addition, 100 mg/kg Kineret(r) significantly decreased severe hemorrhage, degeneration and inflammatory signs in the follicular cells, caused by IR. Kineret(r) at 100 mg/kg markedly ameliorated increased apoptosis in ovarian tissue with IR more significantly than 50 mg/kg kineret. CONCLUSION: Our findings indicate that Kineret(r) might be useful in clinical practice for the treatment of damage that may occur as a result of ovarian torsion. PMID- 27557617 TI - Erratum: Efficient second-harmonic imaging of collagen in histological slides using Bessel beam excitation. PMID- 27557616 TI - Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer. AB - Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n = 167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1 - 1.5 years HR: 1.61 (95%CI: 1.36 - 1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 3 - 4 years HR: 1.17 (95% CI: 0.98 - 1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65 - 0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM. PMID- 27557618 TI - Blacks' Death Rate Due to Circulatory Diseases Is Positively Related to Whites' Explicit Racial Bias. AB - Perceptions of racial bias have been linked to poorer circulatory health among Blacks compared with Whites. However, little is known about whether Whites' actual racial bias contributes to this racial disparity in health. We compiled racial-bias data from 1,391,632 Whites and examined whether racial bias in a given county predicted Black-White disparities in circulatory-disease risk (access to health care, diagnosis of a circulatory disease; Study 1) and circulatory-disease-related death rate (Study 2) in the same county. Results revealed that in counties where Whites reported greater racial bias, Blacks (but not Whites) reported decreased access to health care (Study 1). Furthermore, in counties where Whites reported greater racial bias, both Blacks and Whites showed increased death rates due to circulatory diseases, but this relationship was stronger for Blacks than for Whites (Study 2). These results indicate that racial disparities in risk of circulatory disease and in circulatory-disease-related death rate are more pronounced in communities where Whites harbor more explicit racial bias. PMID- 27557619 TI - Aging of the Liver: What This Means for Patients with HIV. AB - As the HIV population continues to live longer as a result of antiretroviral therapy, liver-related mortality has become one of the leading causes of non-AIDS related death in this patient population. The liver possesses a remarkable regenerative capacity but undergoes complex biological changes in response to aging and inflammation that result in decreased cellular regeneration and a tipping of the scales towards fibrogenesis. Patients with HIV infection have serological evidence of ongoing inflammation, with elevations in some biomarkers persisting despite adequate virologic control. In addition, HIV-co-infected patients have markers of advanced age on liver biopsy and increased prevalence of fibrosis as compared to an age-matched HCV mono-infected cohort. In this review, we will discuss the biology of aging, age-related changes in the liver, and the relevant mechanisms by which HIV causes inflammation in the context of accelerated aging, fibrosis of the liver, and other viral co-infection. PMID- 27557620 TI - Phase-amplitude coupling at the organism level: The amplitude of spontaneous alpha rhythm fluctuations varies with the phase of the infra-slow gastric basal rhythm. AB - A fundamental feature of the temporal organization of neural activity is phase amplitude coupling between brain rhythms at different frequencies, where the amplitude of a higher frequency varies according to the phase of a lower frequency. Here, we show that this rule extends to brain-organ interactions. We measured both the infra-slow (~0.05Hz) rhythm intrinsically generated by the stomach - the gastric basal rhythm - using electrogastrography, and spontaneous brain dynamics with magnetoencephalography during resting-state with eyes open. We found significant phase-amplitude coupling between the infra-slow gastric phase and the amplitude of the cortical alpha rhythm (10-11Hz), with gastric phase accounting for 8% of the variance of alpha rhythm amplitude fluctuations. Gastric-alpha coupling was localized to the right anterior insula, and bilaterally to occipito-parietal regions. Transfer entropy, a measure of directionality of information transfer, indicates that gastric-alpha coupling is due to an ascending influence from the stomach to both the right anterior insula and occipito-parietal regions. Our results show that phase-amplitude coupling so far only observed within the brain extends to brain-viscera interactions. They further reveal that the temporal structure of spontaneous brain activity depends not only on neuron and network properties endogenous to the brain, but also on the slow electrical rhythm generated by the stomach. PMID- 27557621 TI - Ultrasonography of inferior vena cava to determine central venous pressure: a meta-analysis and meta-regression. AB - Background Until now, no valid alternative exists for predicting central venous pressure (CVP) with lower invasiveness than central venous catheter. Purpose To explore inferior vena cava diameter (IVCD) measurement accuracy by ultrasonography as a surrogate variable for determination of central venous pressure (CVP). Material and Methods A systematic review and meta-analysis of all published studies in PubMed, Scopus, Web of Knowledge, and Google Scholar were conducted from inception to July 2013. We used the STROBE checklist for quality assessment and meta-regression. Results Thirty-seven papers with 2843 cases were identified. The correlation coefficients between each one of IVCD, inspiratory IVC (iIVC), IVC collapsibility index (IVCCI), and expiratory IVC (eIVC) with CVP, were 0.68, 0.60, 0.54, and 0.44, respectively. There was no evidence of publication bias ( P = 0.28). Based on meta-regression, male gender was an important source of heterogeneity (OR = 1.01; 95% confidence interval, 1-1.03), which resulted in a higher correlation between IVCD and CVP. The present study showed a higher strength of association with CVP pertaining to IVCD, iIVC, IVCCI, and eIVC, respectively, and they were higher in men. Conclusion This study does not support the measurement of IVCD by ultrasonography as an acceptable surrogate variable to determine CVP among critical patients. PMID- 27557623 TI - Frailty syndrome in patients with heart rhythm disorders. AB - AIM: To assess the prevalence of frailty syndrome in patients with heart rhythm disorders that qualified for pacemaker implantation. METHODS: The study included 171 patients (83 women, aged 73.9 +/- 6.7 years) who qualified for pacemaker implantation as a result of sinus node dysfunction (81 patients) or atrio ventricular blocks (AVB; 90 patients). A total of 60 patients (25 women, aged 72.40 +/- 7.09 years) without heart rhythm disorders were included in the control group. Frailty syndrome was diagnosed using the Canadian Study of Health and Aging Clinical Frailty Scale test. RESULTS: Frailty syndrome was diagnosed in 25.15% of the patients, and pre-frailty in 36.84% of the patients. Frailty syndrome was diagnosed in 10% of the control group, and the average value of frailty was 3.35 +/- 0.92. Frailty occurred significantly more often among patients with AVB (33.34%) compared with patients who were diagnosed with sinus node dysfunction (16.05%); P = 0.0081. The average score of frailty for sinus node dysfunction was 3.71 +/- 0.89, and for AVB it was 4.14 +/- 0.93; P = 0.0152. In the case of AVB, the women had a statistically more intense level of frailty of 4.54 +/- 0.90 as compared with the men 3.87 +/- 0.85; P = 0.0294. In the multiple logistic analysis, the presence of any arrhythmia was strongly associated with frailty syndrome (OR 2.1286, 95% CI 1.4594 - 3.1049; P = 0.0001). CONCLUSIONS: Frailty syndrome was diagnosed in one-quarter of patients with cardiac arrhythmias, whereas a further 40% were at a higher risk of frailty syndrome, and its occurrence was significantly higher if compared with the control group. Frailty occurred significantly more often among patients with atrio-ventricular blocks, especially in women. The results of the present research showed that there is a statistical association between frailty and arrhythmias. Geriatr Gerontol Int 2017; 17: 1313-1318. PMID- 27557624 TI - Reactivity of p-Toluenesulfonylmethyl Isocyanide: Iron-Involved C-H Tosylmethylation of Imidazopyridines in Nontoxic Media. AB - A novel iron-involved tosylmethylation of imidazo[1,2-alpha]pyridines with p toluenesulfonylmethyl isocyanide in a solvent mixture of H2O and PEG400 under an Ar atmosphere has been developed. This protocol provides a facile synthetic route for the functionalization of the imidazo[1,2-alpha]pyridine scaffold with broad substrate compatibility, which is less expensive and environmentally friendly. The current methodology could further enable regioselective C-H tosylmethylation of indole at the C3 position. Also, p-toluenesulfonylmethyl isocyanide was utilized as the tosylmethylating reagent for the first time. PMID- 27557622 TI - Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells. AB - Autotaxin (ATX; also known as ENPP2), the lysophospholipase responsible for generating the lipid receptor agonist lysophosphatidic acid (LPA), is a secreted enzyme. Here we show that, once secreted, ATX can bind to the surface of cell secreted exosomes. Exosome-bound ATX is catalytically active and carries generated LPA. Once bound to a cell, through specific integrin interactions, ATX releases the LPA to activate cell surface G-protein-coupled receptors of LPA; inhibition of signalling by the receptor antagonist Ki1642 suggests that these receptors are LPAR1 and LPAR3. The binding stimulates downstream signalling, including phosphorylation of AKT and mitogen-activated protein kinases, the release of intracellular stored Ca2+ and cell migration. We propose that exosomal binding of LPA-loaded ATX provides a means of efficiently delivering the lipid agonist to cell surface receptors to promote signalling. We further propose that this is a means by which ATX-LPA signalling operates physiologically. PMID- 27557626 TI - Chapter 6 - Oral medication. PMID- 27557625 TI - Using mixed methods case-series evaluation in the development of a guided self management hybrid CBT and ACT intervention for multiple sclerosis pain. AB - PURPOSE: Two-thirds of the people with multiple sclerosis (pwMS) experience pain. Medications provide minimal relief, and current non-pharmacological interventions lack a clear conceptualization of MS pain. This study explored the potential efficacy of a telephone-supported hybrid cognitive behavior therapy and acceptance and commitment therapy self-management intervention for pwMS based on an empirically supported model of MS pain using a replicated single-case series design. METHODS: Seven pwMS with varied demographic and disease characteristics completed the 8-week home-based program alongside 3 hours of telephone support. Online questionnaires were completed every four days for 16 weeks (4-weeks baseline, 8-weeks treatment, 4-weeks follow-up). The primary outcomes were pain severity and pain interference. Psychological process variables drawn from the MS pain model were also completed, and post-treatment qualitative interviews conducted. RESULTS: Simulation modeling analysis (SMA) showed three patients had large improvements in pain outcomes, two showed no change and two worsened. Five participants showed significant change on various psychological process variables. Change in pain catastrophizing was the most consistent finding. CONCLUSIONS: The findings suggest a self-management program for MS pain with minimal therapy support may be effective for some pwMS, but not those with more complex comorbidities. The participants suggested web-based delivery may simplify the approach, and therapist telephone contact was highly valued. Implications for Rehabilitation This case series suggests a hybrid CBT/ACT self-management workbook program for MS pain improves severity and impact of pain in some pwMS. Pain-related catastrophizing reduced in most pwMS, whilst change in other ACT and CBT process variables varied across the individuals. PwMS feedback suggests a tailored web-based delivery of the program with therapist telephone support may be optimal. PwMS with serious co-morbid depression and very advanced disease may not respond well to this self-management approach. PMID- 27557627 TI - PTK7 regulates radioresistance through nuclear factor-kappa B in esophageal squamous cell carcinoma. AB - Tumor radioresistance is a major reason for decreased efficiency of cancer radiation therapy. Although a number of factors involved in radioresistance have been identified, the molecular mechanisms underlying radioresistance of esophageal squamous cell carcinoma (ESCC) have not been elucidated. In this study, we investigated the role of oncogenic protein tyrosine kinase 7 (PTK7) in the resistance of ESCC to radiation therapy. ESCC cell lines with high PTK7 expression were more refractive to radiation than those with low PTK7 levels. In radioresistant ESCC cells, PTK7 knockdown by specific siRNAs decreased the survival of irradiated cells and increased radiation-induced apoptosis, while in radiosensitive ESCC cells, PTK7 overexpression promoted cell survival and inhibited radiation-induced apoptosis. We hypothesized that PTK7 could regulate the activation of transcription factor NF-kB known for its role in cancer radioresistance. Our results indicated that the inhibition of PTK7 suppressed nuclear translocation of NF-kB subunit p65 induced by radiation, suggesting relevance of PTK7 expression with NF-kB activation in radioresistant ESCC. Furthermore, the levels of inhibitor of apoptosis proteins (IAPs), XIAP, and survivin, encoded by NF-kB-regulated genes, were induced in irradiated radioresistant cells but not in radiosensitive cells, while PTK7 knockdown downregulated IAP expression. Our findings revealed a novel mechanism underlying radioresistance in ESCC, which is associated with PTK7 and NF-kB-dependent apoptosis. These results suggest that the manipulation of PTK7 expression can be instrumental in enhancing ESCC response to radiotherapy. This study demonstrates that PTK7 plays a significant role in ESCC radioresistance via the NF-kB pathway. PMID- 27557629 TI - Differences in Antiproliferative Activity Between Salinomycin-AZT Conjugates Obtained via 'Click' and Esterification Reactions. AB - BACKGROUND: Pharmacophore hybridization by bioconjugation, in which two bioactive moieties are covalently linked, is one of the current strategies in drug discovery for the development of new compounds with improved affinity and efficacy relative to those of the parent molecules. Prompted by the idea that cancer cells may be effectively killed by 3'-azido-3'-deoxythymidine (AZT) and salinomycin (SAL) individually, we synthesized hybrids of these compounds. The development of this type of derivatives, which can easily penetrate the lipid rich cell membranes and then undergo hydrolysis inside the cancer cells, is an important research area. METHODS: Efficient methods for the synthesis of two new conjugates are presented. The first method is based on the 'click' chemistry and involves the copper(I) catalysed 1,3-dipolar Huisgen cycloaddition reaction. In the second method AZT as well as SAL are connected by the ester bond under mild reaction conditions. The in vitro anti-proliferative activity of both conjugates against several drugsensitive and drug-resistant cancer cell lines as well as toxicity against normal murine embryonic fibroblasts are also determined. RESULTS: Our studies clearly showed that the hybrid obtained via esterification reaction (SAL-OAZT) seems to be attractive in the fight against neoplastic diseases because it helps to overcome a strong drug-resistance of the cancer cell lines examined at low micromolar concentrations. The anticancer activity of this hybrid is also connected with high selectivity indexes (low toxicity) against normal cells.On the other hand, the 'click' conjugate (SAL-AZT) is practically inactive against the drug-resistant cancer cell lines tested and weakly active against the drug-sensitive ones. Also no synergistic effect has been found between SAL and AZT against eight cancer cell lines studied. CONCLUSION: All of our findings support a strategy to decrease the doxorubicin concentration in combination with SAL-O-AZT hybrid in order to reduce the toxicity of this drug, as recently demonstrated for SAL. The advantages of the SAL-O-AZT conjugate over SAL are better RI and SI parameters at similar IC50values. PMID- 27557628 TI - Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5. AB - Whether transcriptional regulators are functionally involved in mitosis is a fundamental question in cell biology. Here we report that the RNF20/40 complex, a major ubiquitin ligase catalysing histone H2B monoubiquitination, interacts with the motor protein Eg5 during mitosis and participates in spindle assembly. We show that the RNF20/40 complex monoubiquitinates and stabilizes Eg5. Loss of RNF20/40 results in spindle assembly defects, cell cycle arrest and apoptosis. Consistently, depletion of either RNF20/40 or Eg5 suppresses breast cancer in vivo. Significantly, RNF20/40 and Eg5 are concurrently upregulated in human breast carcinomas and high Eg5 expression is associated with poorer overall survival of patients with luminal A, or B, breast cancer. Our study uncovers an important spindle assembly role of the RNF20/40 complex, and implicates the RNF20/40-Eg5 axis in breast carcinogenesis, supporting the pursuit of these proteins as potential targets for breast cancer therapeutic interventions. PMID- 27557630 TI - Strategies for assessing renal function prior to outpatient contrast-enhanced CT: a UK survey. AB - OBJECTIVE: To identify current UK screening practices prior to contrast-enhanced CT. To determine the patient management strategies to minimize the risk of contrast-induced acute kidney injury (CI-AKI) risk in outpatients. METHODS: An invitation to complete an electronic survey was distributed to the CT managers of 174 UK adult National Health Service hospital trusts. The survey included questions related to local protocols and national guidance on which these are based. Details of the assessment of renal function prior to imaging and thresholds for contrast contraindication and patient management were also sought. RESULTS: A response rate of 47.1% was received. Almost all sites had a policy in place for contrast administration (n = 80/82; 97.6%). The majority of sites require a blood test on outpatients undergoing a contrast-enhanced CT scan (n = 75/82; 91.5%); however, some (15/75; 20.0%) sites only check the result in patients at high risk and a small number (7/82; 8.5%) of sites indicated that it was a referrer responsibility. The estimated glomerular filtration rate (eGFR) or serum creatinine (SCr) result threshold at which i.v. contrast was contraindicated varied and 19 different threshold levels of eGFR or SCr were identified, each leading to different prophylactic strategies. Inconsistency was noted in the provision of follow-up blood tests after contrast administration. CONCLUSION: The wide variation in practice reflects inconsistencies in published guidance. Evidence-based consensuses of which patients to test and subsequent risk thresholds will aid clinicians identify those patients in which the risk of CI-AKI is clinically significant but manageable. There is also a need to determine the value of the various prophylactic strategies, follow-up regimen and efficient service delivery pathways. Advances in knowledge: This survey has identified that further work is required to define which patients are high risk, confirm those which require renal function testing prior to contrast administration and how best to manage patients at risk of CI-AKI. The role of new technologies within this service delivery pathway requires further investigation. PMID- 27557631 TI - Effects of TGF-beta1 on mineralization mediated by rat calvaria-derived osteogenic cells. AB - In this study, we have analyzed the viability and cell growth, as well as, the mineralization of extracellular matrix (ECM) by alizarin red and von Kossa staining of calvaria-derived osteogenic cultures, treated with TGF-beta1 alone or associated with Dex comparing with acid ascorbic (AA) + beta-glicerophosphate (betaGP) (positive mineralization control). The expression of the noncollagenous proteins bone sialoprotein (BSP), osteopontin (OPN) and fibronectin (FN) were evaluated by indirect immunofluorescence. In addition, the main ultrastructural morphological findings were assessed by transmission electron microscopy. Osteogenic cells were isolated of calvaria bone from newborn (2-day-old) Wistar rats were treated with TGF-beta1 alone or with dexamethasone for 7, 10, and 14 days. As positive mineralization control, the cells were supplemented only with AA+ betaGP. As negative control, the cells were cultured with basal medium (alpha MEM + 10%FBS + 1%gentamicin). The treatment with TGF-beta1, even when combined with Dex, decreased the viability and cell growth when compared with the positive control. Osteoblastic cell cultures were positive to alizarin red and von Kossa stainings after AA + betaGP and Dex alone treatments. Positive immunoreaction was found for BSP, OPN and FN in all studied treatments. Otherwise, when the cell cultures were supplemented with TGF-beta1 and TGF-beta1 + Dex, no mineralization was observed in any of the studied periods. These present findings suggest that TGF-beta1, in the studied in vitro doses, inhibits the proliferation and differentiation of osteoblastic cells by impairment of nodule formation. PMID- 27557633 TI - Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish. AB - The Ewing sarcoma family of tumors expresses aberrant EWSR1- (EWS) fusion genes that are derived from chromosomal translocation. Although these fusion genes are well characterized as transcription factors, their formation leaves a single EWS allele in the sarcoma cells, and the contribution that the loss of EWS makes towards disease pathogenesis is unknown. To address this question, we utilized zebrafish mutants for ewsa and tp53. The zebrafish tp53(M214K)(w/m) line and the ewsa(w/m), zygotic ewsa(m/m), and Maternal-Zygotic (MZ) ewsa(m/m) lines all displayed zero to low incidence of tumorigenesis. However, when the ewsa and tp53 mutant lines were crossed with each other, the incidence of tumorigenesis drastically increased. Furthermore, 27 hour post fertilization (hpf) MZ ewsa(m/m) mutant embryos displayed a higher incidence of aberrant chromosome numbers and mitotic dysfunction compared to wildtype zebrafish embryos. Consistent with this finding, tumor samples obtained from ewsa(m/m);tp53(w/m) zebrafish displayed loss of heterozygosity (LOH) for the wildtype tp53 locus. These results suggest that wildtype Ewsa inhibits LOH induction, possibly by maintaining chromosomal stability. We propose that the loss of ewsa promotes tumorigenesis, and EWS deficiency may contribute to the pathogenesis of EWS-fusion-expressing sarcomas. PMID- 27557632 TI - HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common neurodegenerative disease, but it remains an intractable condition. Its pathogenesis is predominantly attributed to the aggregation and transmission of two molecules, Abeta and tau; however, other pathological mechanisms are possible. Here, we reveal that phosphorylation of MARCKS, a submembrane protein that regulates the stability of the actin network, occurs at Ser46 prior to aggregation of Abeta and is sustained throughout the course of AD in human and mouse brains. Furthermore, HMGB1 released from necrotic or hyperexcitatory neurons binds to TLR4, triggers the specific phosphorylation of MARCKS via MAP kinases, and induces neurite degeneration, the classical hallmark of AD pathology. Subcutaneous injection of a newly developed monoclonal antibody against HMGB1 strongly inhibits neurite degeneration even in the presence of Abeta plaques and completely recovers cognitive impairment in a mouse model. HMGB1 and Abeta mutually affect polymerization of the other molecule, and the therapeutic effects of the anti-HMGB1 monoclonal antibody are mediated by Abeta-dependent and Abeta-independent mechanisms. We propose that HMGB1 is a critical pathogenic molecule promoting AD pathology in parallel with Abeta and tau and a new key molecular target of preclinical antibody therapy to delay the onset of AD. PMID- 27557634 TI - Serum protein profiling in diffuse large B-cell lymphoma. AB - PURPOSE: The aim of this pilot study was to conduct a nontargeted exploratory proteomics profiling analysis on sera obtained from patients diagnosed with diffuse large B-cell lymphoma (DLBCL) with the goal of identifying disease specific biomarkers. EXPERIMENTAL DESIGN: Sera from 87 participants (57 chemotherapy-naive diffuse DLBCL patients, 30 controls frequency-matched by age group and World Health Organization (WHO) BMI categories) that were part of a large San Francisco Bay Area case-control study of non-Hodgkin lymphoma were analyzed by liquid chromatography combined with tandem mass spectrometry. RESULTS: Thirty-five proteins (p-adjusted <0.05) were identified as differentially abundant between the DLBCL patients at various disease stages as compared to the controls. Of these, five proteins were randomly selected for further confirmation by ELISA: adiponectin (AdipoQ), cluster of differentiation 14 (CD14), heparin sulfate proteoglycan core protein (HSPG2), extracellular matrix 1 (ECM1), and alpha-1-antichymotrypsin (ACT). These proteins were statistically significantly elevated by 68.8, 37.0, 61.6, 68.0, and 32.0%, respectively, in DLBCL patient sera as compared to controls. CONCLUSION AND CLINICAL RELEVANCE: These preliminary data when combined with other cancer related data regarding these proteins warrant continued research in clinical and large prospective studies to clarify the role for these biomarkers in DLBCL pathogenesis and/or prognosis. PMID- 27557635 TI - Factors that predict recurrence later than 5 years after initial treatment in operable breast cancer. AB - BACKGROUND: Occasionally, breast cancer relapses more than 5 years after initial treatment, sometimes with highly aggressive disease in such late-recurring patients. This study investigated predictors of recurrence after more than 5 years in operable breast cancer. METHODS: We retrospectively analyzed data from patients with recurrent breast cancer treated at Siriraj Hospital. Patients were divided into those whose relapse times were longer or shorter than 5 years. Factors that predicted late recurrence were analyzed in both the overall population and the luminal subgroup. Patterns of relapse, changes in biomarkers, and time to disease progression after first relapse were also recorded. RESULTS: We included 300 women whose breast cancers recurred between 2005 and 2013, of whom 180 had recurrence within 5 years of diagnosis and 120 later than 5 years (median time to recurrence: 45.43 months; range: 4.4-250.3 months). Tumors larger than 2 cm, lymph node metastasis, and high nuclear grade were related with early recurrence. Estrogen receptor-positive, progesterone receptor-positive, and HER2( ) disease predicted late recurrence. Almost all late-relapsing patients with luminal tumors had high estrogen receptor (ER(+)) titers (>=50 %) and HER2(-) disease. Liver and brain were the most common early recurrence sites. Biomarkers did not significantly change by time of recurrence. CONCLUSIONS: ER(+)/PR(+) and HER2(-) patients have higher risk of recurrence later than 5 years, especially in patients with high ER titer and low nuclear grade. Larger and node-positive tumors had higher risk of early recurrence. PMID- 27557636 TI - Long non-coding RNAs link extracellular matrix gene expression to ischemic cardiomyopathy. AB - Aims: Ischemic cardiomyopathy (ICM) resulting from myocardial infarction is a major cause of heart failure (HF). Recently, thousands of long non-coding RNAs (lncRNAs) have been discovered and implicated in a variety of biological processes. However, the role of most lncRNAs in HF remains largely unknown. The aim of this study is to test the hypothesis that the expression and function of lncRNAs are differentially regulated in diseased hearts. Methods and results: In this study, we performed RNA deep sequencing of protein-coding and non-coding RNAs from cardiac samples of patients with ICM ( n = 15) and controls ( n = 15). Genome-wide transcriptome analysis confirmed that many protein-coding genes previously known to be involved in HF were altered in ICM hearts. Among the 145 differentially expressed lncRNAs identified in ICM hearts, we found a set of 35 lncRNAs that display strong positive expression correlation. Expression correlation coefficient analyses of differentially expressed lncRNAs and protein coding genes revealed a strong association between lncRNAs and extracellular matrix (ECM) protein-coding genes. We overexpressed or knocked down selected lncRNAs in cardiac fibroblasts and our results suggest that lncRNAs are important regulators of fibrosis and the expression of ECM synthesis genes. Moreover, we show that lncRNAs participate in the TGF-beta pathway to modulate the expression of ECM genes and myofibroblast differentiation. Conclusion: Our studies demonstrate that the expression of many lncRNAs is dynamically regulated in ICM. lncRNAs regulate the expression and function of ECM and cardiac fibrosis during the development of ICM. Our results further indicate that lncRNAs may represent novel regulators of heart function and cardiac disorders, including ICM. PMID- 27557639 TI - Collagenous Colitis Refractory to Budesonide: is the Upper Gastrointestinal Tract Involved? PMID- 27557638 TI - High-specificity synthesis of novel monomers by remodeled alcohol hydroxylase. AB - BACKGROUND: Diols are important monomers for the production of plastics and polyurethanes, which are widely used in our daily life. The medium-chain diols with one hydroxyl group at its subterminal end are able to confer more flexibility upon the synthesized materials. But unfortunately, this type of diols has not been synthesized so far. The strong need for advanced materials impelled us to develop a new strategy for the production of these novel diols. In this study, we use the remodeled P450BM3 for high-specificity production of 1,7 decanediol. RESULTS: The native P450BM3 was capable of converting medium-chain alcohols into corresponding alpha, omega1-, alpha, omega2- and alpha, omega3 diols, with each of them accounting for about one third of the total diols, but it exhibited a little or no activity on the short-chain alcohols. Greatly improved regiospecificity of alcohol hydroxylation was obtained by laboratory evolution of P450BM3. After substitution of 12 amino acid residues (J2-F87A), the ratio of 1,7-decanediol (omega-3 hydroxylation) to total decanediols increased to 86.8 % from 34.0 %. Structure modeling and site-directed mutagenesis demonstrated that the heme end residues such as Ala(78), Phe(87) and Arg(255) play a key role in controlling the regioselectivity of the alcohol hydroxylation, while the residues at the mouth of substrate binding site is not responsible for the regioselectivity. CONCLUSIONS: Herein we employ an engineered P450BM3 for the first time to enable the high-specificity biosynthesis of 1,7-decanediol, which is a promising monomer for the development of advanced materials. Several key amino acid residues that control the regioselectivity of alcohol hydroxylation were identified, providing some new insights into how to improve the regiospecificity of alcohol hydroxylation. This report not only provides a good strategy for the biosynthesis of 1,7-decanediol, but also gives a promising approach for the production of other useful diols. PMID- 27557640 TI - Long-term effects of smoking on tooth loss after cessation among middle-aged Finnish adults: the Northern Finland Birth Cohort 1966 Study. AB - BACKGROUND: Despite smoking cessation efforts, cigarette smoking remains a serious general and oral health problem. We aimed to investigate the putative benefits of smoking cessation on dentition and to analyse whether the time elapsed since smoking cessation associated positively with the remaining number of teeth. METHODS: This cross-sectional study analyses data from the 46-year follow-up of the Northern Finland Birth Cohort Study 1966 (NFBC1966). A total of 5 540 subjects participated in this cross-sectional study, which utilises both clinical dental examinations and mailed questionnaires. We used the following information on smoking: status (current, former, never), years of smoking (current, former) and years elapsed since smoking cessation (former). Self reported and clinically measured number of teeth (including third molars) served as alternative outcomes. We used binary logistic regression models to analyse the dichotomised number of teeth ('0-27', '28-32') and then calculated unadjusted and adjusted odds ratios (OR) with 95 % confidence intervals (CI) for the smoking variables (never smoker as the reference). Gender, education, tooth brushing frequency, diabetes and alcohol use served as confounders for the adjusted models. RESULTS: Ten years or more of smoking associated with tooth loss; this effect was the strongest among men who reported having an ongoing smoking habit (self-reported outcome: adjusted OR = 1.74, CI = 1.40-2.16) and the weakest among women classified as former smokers (self-reported outcome: adjusted OR = 1.27, CI = 1.00-1.62). CONCLUSIONS: This study shows that smoking has long-term effects on tooth loss even after cessation. The findings support smoking cessation efforts to reduce oral health risks. PMID- 27557642 TI - A computational approach to compare regression modelling strategies in prediction research. AB - BACKGROUND: It is often unclear which approach to fit, assess and adjust a model will yield the most accurate prediction model. We present an extension of an approach for comparing modelling strategies in linear regression to the setting of logistic regression and demonstrate its application in clinical prediction research. METHODS: A framework for comparing logistic regression modelling strategies by their likelihoods was formulated using a wrapper approach. Five different strategies for modelling, including simple shrinkage methods, were compared in four empirical data sets to illustrate the concept of a priori strategy comparison. Simulations were performed in both randomly generated data and empirical data to investigate the influence of data characteristics on strategy performance. We applied the comparison framework in a case study setting. Optimal strategies were selected based on the results of a priori comparisons in a clinical data set and the performance of models built according to each strategy was assessed using the Brier score and calibration plots. RESULTS: The performance of modelling strategies was highly dependent on the characteristics of the development data in both linear and logistic regression settings. A priori comparisons in four empirical data sets found that no strategy consistently outperformed the others. The percentage of times that a model adjustment strategy outperformed a logistic model ranged from 3.9 to 94.9 %, depending on the strategy and data set. However, in our case study setting the a priori selection of optimal methods did not result in detectable improvement in model performance when assessed in an external data set. CONCLUSION: The performance of prediction modelling strategies is a data-dependent process and can be highly variable between data sets within the same clinical domain. A priori strategy comparison can be used to determine an optimal logistic regression modelling strategy for a given data set before selecting a final modelling approach. PMID- 27557641 TI - Scaling-up an efficacious school-based physical activity intervention: Study protocol for the 'Internet-based Professional Learning to help teachers support Activity in Youth' (iPLAY) cluster randomized controlled trial and scale-up implementation evaluation. AB - BACKGROUND: Despite the health benefits of regular physical activity, most children are insufficiently active. Schools are ideally placed to promote physical activity; however, many do not provide children with sufficient in school activity or ensure they have the skills and motivation to be active beyond the school setting. The aim of this project is to modify, scale up and evaluate the effectiveness of an intervention previously shown to be efficacious in improving children's physical activity, fundamental movement skills and cardiorespiratory fitness. The 'Internet-based Professional Learning to help teachers support Activity in Youth' (iPLAY) study will focus largely on online delivery to enhance translational capacity. METHODS/DESIGN: The intervention will be implemented at school and teacher levels, and will include six components: (i) quality physical education and school sport, (ii) classroom movement breaks, (iii) physically active homework, (iv) active playgrounds, (v) community physical activity links and (vi) parent/caregiver engagement. Experienced physical education teachers will deliver professional learning workshops and follow-up, individualized mentoring to primary teachers (i.e., Kindergarten - Year 6). These activities will be supported by online learning and resources. Teachers will then deliver the iPLAY intervention components in their schools. We will evaluate iPLAY in two complementary studies in primary schools across New South Wales (NSW), Australia. A cluster randomized controlled trial (RCT), involving a representative sample of 20 schools within NSW (1:1 allocation at the school level to intervention and attention control conditions), will assess effectiveness and cost-effectiveness at 12 and 24 months. Students' cardiorespiratory fitness will be the primary outcome in this trial. Key secondary outcomes will include students' moderate-to-vigorous physical activity (via accelerometers), fundamental movement skill proficiency, enjoyment of physical education and sport, cognitive control, performance on standardized tests of numeracy and literacy, and cost-effectiveness. A scale-up implementation study guided by the RE-AIM framework will evaluate the reach, effectiveness, adoption, implementation, and maintenance of the intervention when delivered in 160 primary schools in urban and regional areas of NSW. DISCUSSION: This project will provide the evidence and a framework for government to guide physical activity promotion throughout NSW primary schools and a potential model for adoption in other states and countries. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ( ACTRN12616000731493 ). Date of registration: June 3, 2016. PMID- 27557644 TI - Elderly hospitalization and the New-type Rural Cooperative Medical Scheme (NCMS) in China: multi-stage cross-sectional surveys of Jiangxi province. AB - BACKGROUND: Studies assessing the impacts of China's New-type Rural Cooperative Medical Scheme (NCMS) reform of 2003 among rural elderly have been limited. METHOD: Multistage stratified cluster sampling household surveys of 1838, 1924, 1879, 1888, 1890 and 1896 households from 27 villages in Jiangxi province were conducted in 2003/2004, 2006, 2008, 2010, 2012 and 2014. Data from older adults age 65 and above were analyzed. Weighted logistic regression was applied to find factors of elderly hospitalization services. RESULTS: Since 2003, hospitalization rates for elderly increased, while rates of patients leaving against medical advice and patients avoiding the hospital decreased (P < 0.05). Factors associated with a higher likelihood of reporting hospitalization in the past year for elderly were the per-capita financial level V in 2012 for NCMS (Adjusted Odds Ratios [aOR]: 2.295), the level VI in 2014 (aOR: 3.045) versus the level I in 2003 and chronic disease (aOR: 2.089) versus not having a chronic disease. Lower rate of elderly left against medical advice was associated with the financial level V in 2012 (aOR: 0.099) versus the level I. The higher rate of hospital avoidance was associated with chronic disease status (aOR: 5.759) versus not having a chronic disease, while the lower rate was associated with the financial level VI in 2014 (aOR: 0.143) versus the level I. Among reporting reasons for elderly hospital avoidance, the cost-related reasons just dropped slightly over the years. CONCLUSIONS: NCMS improved access to health services for older adults. The utilization of hospitalization services for rural elderly increased gradually, but cost-related barriers remained the primary reporting barrier to accessing hospitalization services. PMID- 27557643 TI - Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors. AB - BACKGROUND: Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. METHODS: We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. Mechanistic studies were performed to assess co localization of topoisomerase II alpha (TOP2A), DNA damage, and siRNA knockdown of drug targets. RESULTS: Selinexor was found to restore sensitivity of multidrug resistant 8226B25, 8226Dox6, 8226Dox40, and U266PSR human MM cells to doxorubicin to levels found in parental myeloma cell lines. NOD/SCID-gamma mice challenged with drug-resistant or parental U266 human MM and treated with selinexor/PLD had significantly decreased tumor growth and increased survival with minimal toxicity. Selinexor/doxorubicin treatment selectively induced apoptosis in CD138/light-chain-positive MM cells without affecting non-myeloma cells in ex vivo-treated bone marrow aspirates from newly diagnosed or relapsed/refractory MM patients. Selinexor inhibited XPO1-TOP2A protein complexes (proximity ligation assay), preventing nuclear export of TOP2A in both parental and multidrug resistant MM cell lines. Selinexor/doxorubicin treatment significantly increased DNA damage (comet assay/gamma-H2AX) in both parental and drug-resistant MM cells. TOP2A knockdown reversed both the anti-tumor effect and significantly reduced DNA damage induced by selinexor/doxorubicin treatment. CONCLUSIONS: The combination of an XPO1 inhibitor and liposomal doxorubicin was highly effective against acquired drug resistance in in vitro MM models, in in vivo xenograft studies, and in ex vivo samples obtained from patients with relapsed/refractory myeloma. This drug combination synergistically induced TOP2A-mediated DNA damage and subsequent apoptosis. In addition, based on our preclinical data, we have initiated a phase I/II study with the XPO1 inhibitor selinexor and PLD (ClinicalTrials.gov NCT02186834). Initial results from both preclinical and clinical trials have shown significant promise for this drug combination for the treatment of MM. PMID- 27557645 TI - Intestinal tuberculosis masquerading as difficult to treat Crohn disease: a case report. AB - BACKGROUND: Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. CONCLUSION: This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory. PMID- 27557646 TI - Multispecies Purification of Testicular Germ Cells. AB - Advanced methods of cellular purification are required to apply genome technology to the study of spermatogenesis. One approach, based on flow cytometry of murine testicular cells stained with Hoechst-33342 (Ho-FACS), has been extensively optimized and currently allows the isolation of 9 germ cell types. This staining technique is straightforward to implement, highly effective at purifying specific germ cell types and yields sufficient cell numbers for high throughput studies. Ho-FACS is a technique that does not require species-specific markers, but whose applicability to other species is largely unexplored. We hypothesized that, due to the similar cell physiology of spermatogenesis across mammals, Ho-FACS could be used to produce highly purified subpopulations of germ cells in mammals other than mouse. To test this hypothesis, we applied Ho-FACS to 4 mammalian species that are widely used in testis research - Rattus norvegicus, Cavia porcellus, Canis familiaris and Sus scrofa domesticus We successfully isolated 4 germ cell populations from these species with average purity of 79% for spermatocytes, and 90% for spermatids and 66% for spermatogonia. Additionally, we compare the performance of mechanical and chemical dissociation for each species, and propose an optimized gating strategy to better discriminate round and elongating spermatids in the mouse, which can potentially be applied to other species. Our work indicates that spermatogenesis may be uniquely accessible among mammalian developmental systems, as a single set of reagents may be sufficient to isolate germ cell populations from many different mammalian species, opening new avenues in the fields of development and male reproductive biology. PMID- 27557647 TI - Depression-Like Behavior in a Dehydroepiandrosterone-Induced Mouse Model of Polycystic Ovary Syndrome. AB - Patients with polycystic ovary syndrome (PCOS) can suffer from psychological disorders, among which depression is the most commonly diagnosed. However, the pathogenesis is still unclear. The aims of the present study were to investigate the behaviors of dehydroepiandrosterone (DHEA)-induced PCOS mice, the effects of high-fat diet (HFD) on mouse behaviors, and the underlying mechanism. Prepubertal C57BL/6 mice (25 days of age) were divided into four groups and injected daily with the vehicle sesame oil or DHEA on the normal chow or a 60% HFD for 20 consecutive days. Depression-like behavior of the mice was examined using a forced swim test, tail suspension test, and open field test. Thereafter, the animals were killed and four brain regions were collected. The brain levels of monoamines and their metabolites, including norepinephrine, serotonin, 5-hydroxy 3-indolacetic acid, dopamine, and 3,4-hydroxyphenylacetic acid, were analyzed by HPLC. Our data show that DHEA-treated mice exhibited depression-like behavior according to the results from behavioral assessment. The brain contents of monoamines and/or their metabolites decreased in DHEA-treated mice compared with controls. HFD did not seem to markedly affect the behavioral responses, the brain monoamines, or their metabolites in the mice. These findings suggest that DHEA treatment induced depression-like behavior in PCOS mice, possibly through down regulation of brain monoamines and/or their metabolites, which implies the contribution of hyperandrogenism to the psychological symptoms of women with PCOS. PMID- 27557648 TI - Formation and Dissociation of Sperm Bundles in Monotremes. AB - Because monotremes are the earliest offshoot of the mammalian lineage, the platypus and short-beaked echidna were studied as model animals to assess the origin and biological significance of adaptations considered unique to therian mammals: epididymal sperm maturation and subsequent capacitation. We show that spermatozoa from both species assemble into bundles of approximately 100 cells during passage through the epididymis and that an epididymal protein-secreted protein, acidic, cysteine-rich (osteonectin; SPARC)-is involved in bundle formation. The bundles persisted during incubation in vitro for at least 1 h under conditions that capacitate therian spermatozoa, and then underwent a time dependent dissociation to release spermatozoa capable of fertilization. Only after this dissociation could the spermatozoa bind to the perivitelline membrane of a hen's egg, display an altered form of motility reminiscent of hyperactivation, and be induced to undergo an acrosome reaction. It is concluded that the development of sperm bundles in the monotreme epididymis mandates that they require a time-dependent process to be capable of fertilizing an ovum. However, because this functional end point was achieved without overt changes in protein tyrosine phosphorylation (a hallmark of capacitation in therians), it is concluded that the process in monotremes is distinctly different from capacitation in therian mammals. PMID- 27557649 TI - Deconstructing post-exertional malaise: An exploratory factor analysis. AB - Post-exertional malaise is a cardinal symptom of myalgic encephalomyelitis and chronic fatigue syndrome. There are two differing focuses when defining post exertional malaise: a generalized, full-body fatigue and a muscle-specific fatigue. This study aimed to discern whether post-exertional malaise is a unified construct or whether it is composed of two smaller constructs, muscle fatigue and generalized fatigue. An exploratory factor analysis was conducted on several symptoms that assess post-exertional malaise. The results suggest that post exertional malaise is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue. PMID- 27557650 TI - Combined cognitive biases for pain and disability information in individuals with chronic headache: A preliminary investigation. AB - Pain-related cognitive biases have been demonstrated in chronic pain patients, yet despite theoretical predictions are rarely investigated in combination. Combined cognitive biases were explored in individuals with chronic headache ( n = 17) and pain-free controls ( n = 20). Participants completed spatial cueing (attentional bias), sentence generation (interpretation bias) and free recall tasks (memory bias), with ambiguous sensory-pain, disability and neutral words. Individuals with chronic headache, relative to controls, showed significantly greater interpretation and memory biases favouring ambiguous sensory-pain words and interpretation bias favouring ambiguous disability words. No attentional bias was found. Further research is needed exploring the temporal pattern of cognitive biases. PMID- 27557651 TI - Living longer with help from others: Seeking advice lowers mortality risk. AB - Associations between self-sufficiency and advice seeking with mortality risk were examined to assess the long-term implications of individualistic and interpersonally oriented strategies. Wave 1 participants from the National Survey of Midlife Development in the United States ( N = 6116, 25-75 years, Mage = 46.38 years) completed questionnaires assessing demographics, self-sufficiency, advice seeking, social support, and health. Cox proportional hazard models indicated that each standard deviation increase in seeking advice was associated with an 11 percent decreased hazard of dying 20 years later. Self-sufficiency was not significantly related. Future research should examine contexts in which interpersonal strategies are adaptive, as seeking advice from others promotes longevity. PMID- 27557652 TI - Body image dissatisfaction, physical activity and screen-time in Spanish adolescents. AB - This cross-sectional study contributes to the literature on whether body dissatisfaction is a barrier/facilitator to engaging in physical activity and to investigate the impact of mass-media messages via computer-time on body dissatisfaction. High-school students ( N = 1501) reported their physical activity, computer-time (homework/leisure) and body dissatisfaction. Researchers measured students' weight and height. Analyses revealed that body dissatisfaction was negatively associated with physical activity on both genders, whereas computer-time was associated only with girls' body dissatisfaction. Specifically, as computer-homework increased, body dissatisfaction decreased; as computer leisure increased, body dissatisfaction increased. Weight-related interventions should improve body image and physical activity simultaneously, while critical consumption of mass-media interventions should include a computer component. PMID- 27557654 TI - High intake of regular-fat cheese compared with reduced-fat cheese does not affect LDL cholesterol or risk markers of the metabolic syndrome: a randomized controlled trial. AB - BACKGROUND: Regular-fat cheese contains a high amount of saturated fat. Therefore, dietary guidelines in many countries recommend the consumption of reduced-fat cheese as opposed to regular-fat cheese. However, the negative effect of regular-fat cheese is still under debate. OBJECTIVES: The aim was to compare the effects of regular-fat cheese with an equal amount of reduced-fat cheese and an isocaloric amount of carbohydrate-rich foods on LDL cholesterol and risk factors for the metabolic syndrome (MetS). DESIGN: The study was a 12-wk randomized parallel intervention preceded by a 2-wk run-in period. A total of 164 subjects with >=2 MetS risk factors were randomly allocated to 1 of 3 intervention groups: regular-fat cheese (REG), reduced-fat cheese (RED), or a no cheese, carbohydrate control (CHO) group. Subjects in the REG and RED groups replaced part of their daily habitual diet with 80 g cheese/10 MJ, whereas subjects in the CHO group did the same with bread and jam corresponding to 90 g and 25 g/10 MJ, respectively. RESULTS: A total of 139 subjects completed the intervention. The primary outcome, LDL cholesterol, was not significantly different between the REG and RED diets or between the REG and CHO diets. There was no significant difference in HDL cholesterol between the REG and RED diets, but HDL cholesterol tended to be higher with the REG diet than with the CHO diet (0.06 +/- 0.03 mmol/L; P = 0.07). Insulin, glucose, and triacylglycerol concentrations as well as blood pressure and waist circumference did not differ significantly between the 3 diets. CONCLUSION: A high daily intake of regular-fat cheese for 12 wk did not alter LDL cholesterol or MetS risk factors differently than an equal intake of reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods. This trial was registered at www.clinicaltrials.gov as NCT02616471. PMID- 27557653 TI - Associations between blood glucose level and outcomes of adult in-hospital cardiac arrest: a retrospective cohort study. AB - BACKGROUND: We intended to analyse the associations between blood glucose (BG) level and clinical outcomes of in-hospital cardiac arrest (IHCA). METHODS: We conducted a retrospective observational study in a single medical centre and evaluated patients who experienced IHCA between 2006 and 2014. We used multivariable logistic regression analysis to study associations between independent variables and outcomes. We calculated the mean BG level for each patient by averaging the maximum and minimum BG levels in the first 24 h after arrest, and we used mean BG level for our final analysis. RESULTS: We included a total of 402 patients. Of these, 157 patients (39.1 %) had diabetes mellitus (DM). The average mean BG level was 209.9 mg/dL (11.7 mmol/L). For DM patients, a mean BG level between 183 and 307 mg/dL (10.2-17.1 mmol/L) was significantly associated with favourable neurological outcome (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.18-6.20; p value = 0.02); a mean BG level between 147 and 317 mg/dL (8.2-17.6 mmol/L) was significantly associated with survival to hospital discharge (OR 2.38, 95 % CI 1.26-4.53; p value = 0.008). For non-DM patients, a mean BG level between 143 and 268 mg/dL (7.9-14.9 mmol/L) was significantly associated with survival to hospital discharge (OR 2.93, 95 % CI 1.62-5.40; p value < 0.001). CONCLUSIONS: Mean BG level in the first 24 h after cardiac arrest was associated with neurological outcome for IHCA patients with DM. For neurological and survival outcomes, the optimal BG range may be higher for patients with DM than for patients without DM. PMID- 27557655 TI - High red meat intake and all-cause cardiovascular and cancer mortality: is the risk modified by fruit and vegetable intake? AB - BACKGROUND: High red meat consumption is associated with a shorter survival and higher risk of cardiovascular disease (CVD), cancer, and all-cause mortality. Fruit and vegetable (FV) consumption is associated with a longer survival and lower mortality risk. Whether high FV consumption can counterbalance the negative impact of high red meat consumption is unknown. OBJECTIVE: We evaluated 2 large prospective cohorts of Swedish men and women (the Swedish Mammography Cohort and the Cohort of Swedish Men) to determine whether the association between red meat consumption and the risk of all-cause, CVD, and cancer-specific mortality differs across amounts of FV intake. DESIGN: The study population included 74,645 Swedish men and women. Red meat and FV consumption were assessed through a self administered questionnaire. We estimated HRs of all-cause, CVD, and cancer mortality according to quintiles of total red meat consumption. We next investigated possible interactions between red meat and FV consumption and evaluated the dose-response associations at low, medium, and high FV intake. RESULTS: Compared with participants in the lowest quintile of total red meat consumption, those in the highest quintile had a 21% increased risk of all-cause mortality (HR: 1.21; 95% CI: 1.13, 1.29), a 29% increased risk of CVD mortality (HR: 1.29; 95% CI: 1.14, 1.46), and no increase in the risk of cancer mortality (HR: 1.00; 95% CI: 0.88, 1.43). Results were remarkably similar across amounts of FV consumption, and no interaction between red meat and FV consumption was detected. CONCLUSION: High intakes of red meat were associated with a higher risk of all-cause and CVD mortality. The increased risks were consistently observed in participants with low, medium, and high FV consumption. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively. PMID- 27557656 TI - Dairy fat and risk of cardiovascular disease in 3 cohorts of US adults. AB - BACKGROUND: Few prospective studies have examined dairy fat in relation to cardiovascular disease (CVD). OBJECTIVE: We aimed to evaluate the association between dairy fat and incident CVD in US adults. DESIGN: We followed 43,652 men in the Health Professionals Follow-Up Study (1986-2010), 87,907 women in the Nurses' Health Study (1980-2012), and 90,675 women in the Nurses' Health Study II (1991-2011). Dairy fat and other fat intakes were assessed every 4 y with the use of validated food-frequency questionnaires. RESULTS: During 5,158,337 person years of follow-up, we documented 14,815 incident CVD cases including 8974 coronary heart disease cases (nonfatal myocardial infarction or fatal coronary disease) and 5841 stroke cases. In multivariate analyses, compared with an equivalent amount of energy from carbohydrates (excluding fruit and vegetables), dairy fat intake was not significantly related to risk of total CVD (for a 5% increase in energy from dairy fat, the RR was 1.02; 95% CI: 0.98, 1.05), coronary heart disease (RR: 1.03; 95% CI: 0.98, 1.09), or stroke (RR: 0.99; 95% CI: 0.93, 1.05) (P > 0.05 for all). In models in which we estimated the effects of exchanging different fat sources, the replacement of 5% of energy intake from dairy fat with equivalent energy intake from polyunsaturated fatty acid (PUFA) or vegetable fat was associated with 24% (RR: 0.76; 95% CI: 0.71, 0.81) and 10% (RR: 0.90; 95% CI: 0.87, 0.93) lower risk of CVD, respectively, whereas the 5% energy intake substitution of other animal fat with dairy fat was associated with 6% increased CVD risk (RR: 1.06; 95% CI: 1.02, 1.09). CONCLUSIONS: The replacement of animal fats, including dairy fat, with vegetable sources of fats and PUFAs may reduce risk of CVD. Whether the food matrix may modify the effect of dairy fat on health outcomes warrants further investigation. PMID- 27557657 TI - The effects of fat loss after bariatric surgery on inflammation, serum hepcidin, and iron absorption: a prospective 6-mo iron stable isotope study. AB - BACKGROUND: Iron deficiency is common in obese subjects. This may be due to an increase in serum hepcidin and a decrease in iron absorption from adiposity related inflammation. OBJECTIVE: We evaluated whether weight and fat loss in obese subjects would decrease inflammation and serum hepcidin and thereby improve iron absorption. DESIGN: We performed a 6-mo prospective study in obese [body mass index (in kg/m2) >=35 and <45] adults who had recently undergone laparoscopic sleeve gastrectomy. At 2 and 8 mo postsurgery, subjects consumed a test drink with 6 mg 57Fe as ferrous sulfate and were intravenously infused with 100 MUg 58Fe as iron citrate. We then compared erythrocyte incorporation of iron isotopic labels, changes in body composition, iron status, hepcidin, and inflammation at each time point. RESULTS: Forty-three subjects were studied at baseline, and 38 completed the protocol (32 women and 6 men). After 6 mo, total body fat, interleukin IL-6, and hepcidin were significantly lower (all P < 0.005). In iron-deficient subjects (n = 17), geometric mean (95% CI) iron absorption increased by 28% [from 9.7% (6.5%, 14.6%) to 12.4% (7.7%, 20.1%); P = 0.03], whereas in iron-sufficient subjects (n = 21), absorption did not change [5.9% (4.0%, 8.6%) and 5.6% (3.9%, 8.2%); P = 0.81]. CONCLUSION: Adiposity related inflammation is associated with a reduction in the normal upregulation of iron absorption in iron-deficient obese subjects, and this adverse effect may be ameliorated by fat loss. This protocol was approved by the ethics committees of Wageningen University, ETH Zurich, the University of Monterrey, and the Federal Commission for the Protection against Sanitary Risks, and registered at clinicaltrials.gov as NCT01347905. PMID- 27557658 TI - The Structure of the Antibiotic Deactivating, N-hydroxylating Rifampicin Monooxygenase. AB - Rifampicin monooxygenase (RIFMO) catalyzes the N-hydroxylation of the natural product antibiotic rifampicin (RIF) to 2'-N-hydroxy-4-oxo-rifampicin, a metabolite with much lower antimicrobial activity. RIFMO shares moderate sequence similarity with well characterized flavoprotein monooxygenases, but the protein has not been isolated and characterized at the molecular level. Herein, we report crystal structures of RIFMO from Nocardia farcinica, the determination of the oligomeric state in solution with small angle x-ray scattering, and the spectrophotometric characterization of substrate binding. The structure identifies RIFMO as a class A flavoprotein monooxygenase and is similar in fold and quaternary structure to MtmOIV and OxyS, which are enzymes in the mithramycin and oxytetracycline biosynthetic pathways, respectively. RIFMO is distinguished from other class A flavoprotein monooxygenases by its unique middle domain, which is involved in binding RIF. Small angle x-ray scattering analysis shows that RIFMO dimerizes via the FAD-binding domain to form a bell-shaped homodimer in solution with a maximal dimension of 110 A. RIF binding was monitored using absorbance at 525 nm to determine a dissociation constant of 13 MUm Steady-state oxygen consumption assays show that NADPH efficiently reduces the FAD only when RIF is present, implying that RIF binds before NADPH in the catalytic scheme. The 1.8 A resolution structure of RIFMO complexed with RIF represents the precatalytic conformation that occurs before formation of the ternary E-RIF-NADPH complex. The RIF naphthoquinone blocks access to the FAD N5 atom, implying that large conformational changes are required for NADPH to reduce the FAD. A model for these conformational changes is proposed. PMID- 27557659 TI - Pigment Epithelium-derived Factor (PEDF) Blocks Wnt3a Protein-induced Autophagy in Pancreatic Intraepithelial Neoplasms. AB - An increase in autophagy characterizes pancreatic carcinogenesis, but the signals that regulate this process are incompletely understood. Because canonical Wnt/beta-catenin signaling is necessary for the transition from early to advanced pancreatic intraepithelial neoplasia (PanIN) lesions, we assessed whether Wnt ligands and endogenous inhibitors of Wnt signaling modulate autophagy. In this study, canonical Wnt3a ligand induced autophagy markers and vacuoles in murine PanIN cells. Furthermore, pigment epithelium-derived factor (PEDF), a secreted glycoprotein known for its anti-tumor properties, blocked Wnt3a-directed induction of autophagy proteins. Autophagy inhibition was complemented by reciprocal regulation of the oxidative stress enzymes, superoxide dismutase 2 (SOD2) and catalase. Transcriptional control of Sod2 expression was mediated by PEDF-induced NFkappaB nuclear translocation. PEDF-dependent SOD2 expression in PanIN lesions was recapitulated in a murine model of PanIN formation where PEDF was deleted. In human PanIN lesions, co-expression of PEDF and SOD2 was observed in the majority of early PanIN lesions (47/50, 94%), whereas PEDF and SOD2 immunolocalization in high-grade human PanIN-2/3 was uncommon (7/50, 14%). These results indicate that PEDF regulates autophagy through coordinate Wnt signaling blockade and NFkappaB activation. PMID- 27557661 TI - Irregular G-quadruplexes Found in the Untranslated Regions of Human mRNAs Influence Translation. AB - G-quadruplex structures are composed of coplanar guanines and are found in both DNA and RNA. They are formed by the stacking of two or more G-quartets that are linked together by three loops. The current belief is that RNA G-quadruplexes include loops of l to 7 nucleotides in length, although recent evidence indicates that the central loop (loop 2) can be longer if loops 1 and 3 are limited to a single nucleotide each. With the objective of broadening the definition of irregular RNA G-quadruplexes, a bioinformatic search was performed to find potential G-quadruplexes located in the untranslated regions of human mRNAs (i.e. in the 5' and 3'-UTRs) that contain either a long loop 1 or 3 of up to 40 nucleotides in length. RNA molecules including the potential sequences were then synthesized and examined in vitro by in-line probing for the formation of G quadruplex structures. The sequences that adopted a G-quadruplex structure were cloned into a luciferase dual vector and examined for their ability to modulate translation in cellulo Some irregular G-quadruplexes were observed to either promote or repress translation regardless of the position or the size of the long loop they possessed. Even if the composition of a RNA G-quadruplex is not quite completely understood, the results presented in this report clearly demonstrate that what defines a RNA G-quadruplex is much broader than what we previously believed. PMID- 27557660 TI - Phosphorylation of PP1 Regulator Sds22 by PLK1 Ensures Accurate Chromosome Segregation. AB - During cell division, accurate chromosome segregation is tightly regulated by Polo-like kinase 1 (PLK1) and opposing activities of Aurora B kinase and protein phosphatase 1 (PP1). However, the regulatory mechanisms underlying the aforementioned hierarchical signaling cascade during mitotic chromosome segregation have remained elusive. Sds22 is a conserved regulator of PP1 activity, but how it regulates PP1 activity in space and time during mitosis remains elusive. Here we show that Sds22 is a novel and cognate substrate of PLK1 in mitosis, and the phosphorylation of Sds22 by PLK1 elicited an inhibition of PP1-mediated dephosphorylation of Aurora B at threonine 232 (Thr232) in a dose dependent manner. Overexpression of a phosphomimetic mutant of Sds22 causes a dramatic increase in mitotic delay, whereas overexpression of a non phosphorylatable mutant of Sds22 results in mitotic arrest. Mechanistically, the phosphorylation of Sds22 by PLK1 strengthens the binding of Sds22 to PP1 and inhibits the dephosphorylation of Thr232 of Aurora B to ensure a robust, error free metaphase-anaphase transition. These findings delineate a conserved signaling hierarchy that orchestrates dynamic protein phosphorylation and dephosphorylation of critical mitotic regulators during chromosome segregation to guard chromosome stability. PMID- 27557662 TI - Restrictive Cardiomyopathy Troponin I R145W Mutation Does Not Perturb Myofilament Length-dependent Activation in Human Cardiac Sarcomeres. AB - The cardiac troponin I (cTnI) R145W mutation is associated with restrictive cardiomyopathy (RCM). Recent evidence suggests that this mutation induces perturbed myofilament length-dependent activation (LDA) under conditions of maximal protein kinase A (PKA) stimulation. Some cardiac disease-causing mutations, however, have been associated with a blunted response to PKA-mediated phosphorylation; whether this includes LDA is unknown. Endogenous troponin was exchanged in isolated skinned human myocardium for recombinant troponin containing either cTnI R145W, PKA/PKC phosphomimetic charge mutations (S23D/S24D and T143E), or various combinations thereof. Myofilament Ca2+ sensitivity of force, tension cost, LDA, and single myofibril activation/relaxation parameters were measured. Our results show that both R145W and T143E uncouple the impact of S23D/S24D phosphomimetic on myofilament function, including LDA. Molecular dynamics simulations revealed a marked reduction in interactions between helix C of cTnC (residues 56, 59, and 63), and cTnI (residue 145) in the presence of either cTnI RCM mutation or cTnI PKC phosphomimetic. These results suggest that the RCM-associated cTnI R145W mutation induces a permanent structural state that is similar to, but more extensive than, that induced by PKC-mediated phosphorylation of cTnI Thr-143. We suggest that this structural conformational change induces an increase in myofilament Ca2+ sensitivity and, moreover, uncoupling from the impact of phosphorylation of cTnI mediated by PKA at the Ser 23/Ser-24 target sites. The R145W RCM mutation by itself, however, does not impact LDA. These perturbed biophysical and biochemical myofilament properties are likely to significantly contribute to the diastolic cardiac pump dysfunction that is seen in patients suffering from a restrictive cardiomyopathy that is associated with the cTnI R145W mutation. PMID- 27557664 TI - A novel type of splayed ferromagnetic order observed in Yb2Ti2O7. AB - The pyrochlore insulator Yb2Ti2O7 has attracted the attention of experimentalists and theoreticians alike for about 15 years. Conflicting neutron diffraction data on the possible existence of magnetic Bragg reflections at low temperature have been published. Here we report the observation of magnetic Bragg reflections by neutron powder diffraction at 60 mK. The magnetic diffraction pattern is analyzed using representation theory. We find Yb2Ti2O7 to be a splayed ferromagnet as reported for Yb2Sn2O7, a sibling compound with also dominating ferromagnetic interactions as inferred from the positive Curie-Weiss temperature. However, the configuration of the magnetic moment components perpendicular to the easy axis is of the all-in-all-out type in Yb2Ti2O7 while it is two-in-two-out in the Yb2Sn2O7. An overall experimental picture of the magnetic properties emerges. PMID- 27557663 TI - Type I gamma Phosphatidylinositol Phosphate 5-Kinase i5 Controls the Ubiquitination and Degradation of the Tumor Suppressor Mitogen-inducible Gene 6. AB - Mitogen-inducible gene 6 (Mig6) is a tumor suppressor, and the disruption of Mig6 expression is associated with cancer development. Mig6 directly interacts with epidermal growth factor receptor (EGFR) to suppress the activation and downstream signaling of EGFR. Therefore, loss of Mig6 enhances EGFR-mediated signaling and promotes EGFR-dependent carcinogenesis. The molecular mechanism modulating Mig6 expression in cancer remains unclear. Here we demonstrate that type I gamma phosphatidylinositol phosphate 5-kinase i5 (PIPKIgammai5), an enzyme producing phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), stabilizes Mig6 expression. Knockdown of PIPKIgammai5 leads to the loss of Mig6 expression, which dramatically enhances and prolongs EGFR-mediated cell signaling. Loss of PIPKIgammai5 significantly promotes Mig6 protein degradation via proteasomes, but it does not affect the Mig6 mRNA level. PIPKIgammai5 directly interacts with the E3 ubiquitin ligase neuronal precursor cell-expressed developmentally down regulated 4-1 (NEDD4-1). The C-terminal domain of PIPKIgammai5 and the WW1 and WW2 domains of NEDD4-1 are required for their interaction. The C2 domain of NEDD4 1 is required for its interaction with PtdIns(4,5)P2 By binding with NEDD4-1 and producing PtdIns(4,5)P2, PIPKIgammai5 perturbs NEDD4-1-mediated Mig6 ubiquitination and the subsequent proteasomal degradation. Thus, loss of NEDD4-1 can rescue Mig6 expression in PIPKIgammai5 knockdown cells. In this way, PIPKIgammai5, NEDD4-1, and Mig6 form a novel molecular nexus that controls EGFR activation and downstream signaling. PMID- 27557666 TI - No common founder for C9orf72 expansion mutation in Sweden. AB - Hexanucleotide expansion mutations in the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). SNP haplotype analyses have suggested that all C9orf72 expansion mutations originate from a common founder. However, not all C9orf72 expansion mutation carriers have the same haplotype. To investigate if the C9orf72 expansion mutation carriers in Sweden share a common founder, we have genotyped SNPs flanking the C9orf72 expansion mutation in cases with FTD, FTD-ALS or ALS to perform haplotype analysis. We have genotyped 57 SNPs in 232 cases of which 45 carried the C9orf72 expansion mutation. Two risk haplotypes consisting of 31 SNPs, spanning 131 kbp, were found to be significantly associated with the mutation. In summary, haplotype analysis on Swedish C9orf72 expansion mutation carriers indicates that the C9orf72 expansion mutation arose on at least two risk haplotypes. PMID- 27557665 TI - The microRNA signatures: aberrantly expressed microRNAs in head and neck squamous cell carcinoma. AB - microRNAs (miRNAs) are responsible for fine tuning the normal expression of RNA networks in human cells. Accumulating studies have demonstrated that abnormally expressed miRNAs have pivotal roles in the development of head and neck squamous cell carcinoma (HNSCC). Specifically, expression signatures of miRNAs in HNSCC have revealed dysregulated production of miRNAs and the resultant abnormal production of mRNAs and proteins. In this review, we discuss current findings regarding aberrantly expressed miRNAs and their contribution to HNSCC molecular pathogenesis. PMID- 27557667 TI - Estimation of the risk of a qualitative phenotype: dependence on population risk. AB - Individual disease risk estimated based on the data from single or multiple genetic loci is generally calculated using the genotypes of a subject, frequencies of alleles of interest, odds ratios and the average population risk. However, it is often difficult to estimate accurately the average population risk, and therefore it is often expressed as an interval. To better estimate the risk of a subject with given genotypes, we built R scripts using the R environment and constructed graphs to examine the change in the estimated risk as well as the relative risk according to the change of the average population risk. In most cases, the graph of the relative risk did not cross the line of y=1, thereby indicating that the order of the relative risk for given genotypes and the population average risk does not change when the average risk increases or decreases. In rare cases, however, the graph of the relative risk crossed the line of y=1, thereby indicating that the order of the relative risk for given genotypes and the population average risk does change owing to the change in the population risk. We propose that the relative risk should be estimated for not only the point average population risk but also for an interval of the average population risk. Moreover, when the graph crosses the line of y=1 within the interval, this information should be reported to the consumer. PMID- 27557670 TI - From Genesis to Revelation: The Role of Inflammatory Mediators in Chronic Respiratory Diseases and their Control by Nucleic Acid-based Drugs. AB - Asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis, are among the most common chronic diseases and their prevalence is increasing. Each of these diseases is characterized by the secretion of cytokines and pro-inflammatory molecules which are thought to play a critical role in their pathogenesis. Moreover, immune cells, particularly neutrophils, macrophages and dendritic cells as well structural cells such as epithelial and airway smooth muscle cells are also involved in the pathogenic cycle of these diseases. There is a pressing need for the development of new therapies for these pulmonary diseases, particularly as no existing treatment has been shown to reduce disease progression. HMGB1 (high-mobility group box 1), originally identified as a nuclear non histone protein with DNA-binding domains can be secreted by living and dying cells and it is now regarded as an important endogenous danger signaling molecule. Besides as a signal of tissue injury, HMGB1 is considered a powerful mediator of inflammation and high levels of HMGB1 are found in chronic lung diseases. The role of HMGB1 in respiratory diseases is still elusive nevertheless these studies suggest an involvement of this cytokine in their pathogenesis. Nucleic acid-based drugs (NABDs) are a novel class of pharmaceuticals including antisense oligonucleotides, DNA-zymes, and RNA interference as mediated by small interfering RNA (siRNA), which are used to dampen the expression of disease-causing genes having therapeutic potential for controlling chronic airway diseases. Due to their inherent difficulties, such as for example sensitivity to endonucleases, their delivery in vivo should be assured by vectors. Non-viral lipid- and polymer-based nanosystems have acquired much importance in this context. In this review, we will discuss these emerging tools in gene therapy of chronic lung diseases, particularly the use of siRNA in the down-regulation of critical molecules in the pathogenesis of chronic lung diseases, with particular emphasis on HMGB1 as therapeutic target. PMID- 27557669 TI - Characterization of transcription factor response kinetics in parallel. AB - BACKGROUND: Transcription factors (TFs) are effectors of cell signaling pathways that regulate gene expression. TF networks are highly interconnected; one signal can lead to changes in many TF levels, and one TF level can be changed by many different signals. TF regulation is central to normal cell function, with altered TF function being implicated in many disease conditions. Thus, measuring TF levels in parallel, and over time, is crucial for understanding the impact of stimuli on regulatory networks and on diseases. RESULTS: Here, we report the parallel analysis of temporal TF level changes due to multiple stimuli in distinct cell types. We have analyzed short-term dynamic changes in the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), signal transducer and activator of transcription 3 (Stat3), cAMP response element binding protein (CREB), glucocorticoid receptor (GR), and TATA binding protein (TBP), in breast and liver cancer cells after tumor necrosis factor-alpha (TNF alpha) and palmitic acid (PA) exposure. In response to both stimuli, NF-kB and CREB levels were increased, Stat3 decreased, and TBP was constant. GR levels were unchanged in response to TNF-alpha stimulation and increased in response to PA treatment. CONCLUSIONS: Our results show significant overlap in signaling initiated by TNF-alpha and by PA, with the exception that the events leading to PA-mediated cytotoxicity likely also include induction of GR signaling. These results further illuminate the dynamics of TF responses to cytokine and fatty acid exposure, while concomitantly demonstrating the utility of parallel TF measurement approaches in the analysis of biological phenomena. PMID- 27557671 TI - Ex vivo Skin Permeation Evaluation of An Innovative Transdermal Vehicle Using Nimesulide and Piroxicam as Model Drugs. AB - BACKGROUND: The transdermal dosage forms presented a limited usage for a long time, for it was believed that the stratum corneum, the outermost layer of epidermis, made it impracticable the permeation of medications through the skin. Studies exploring this area came up with strategies to overcome this barrier; for example, creating a transdermal vehicle to facilitate the drug absorption. OBJECTIVE: This study aimed to evaluate a new transdermal vehicle through the comparison of its permeation profile and the profile of commercial products, using nimesulide and piroxicam, non steroidal anti-inflammatory drugs. METHODS: Four different products were evaluated: nimesulide and piroxicam compounded with the new vehicle (emulsion) and commercial nimesulide and piroxicam gels. Ex vivo permeation experiments using Franz-type diffusion cell equipment were conducted, using human skin as membrane. For evaluation of permeated active pharmaceutical ingredients concentrations, we performed quantification from the receptor solution, stratum corneum and viable epidermis + dermis, through high-performance liquid chromatography analyses. RESULTS: The new vehicle promoted increased permeation of active pharmaceutical ingredients through the viable epidermis and dermis, when compared to commercial products, but the stratum corrneum continued to keep the highest retention. CONCLUSION: The innovative vehicle was capable of enhancing the transdermal absorption of active pharmaceutical ingredients from the compounded formulations, thus, demonstrating the capability thereof to improve the permeability of active pharmaceutical ingredients by transdermal use. PMID- 27557672 TI - Traversing the Skin Barrier with Nano-emulsions. AB - BACKGROUND: In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes. METHODS: This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed. RESULTS: Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs. CONCLUSION: This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects. PMID- 27557668 TI - Convergent evolution of defensin sequence, structure and function. AB - Defensins are a well-characterised group of small, disulphide-rich, cationic peptides that are produced by essentially all eukaryotes and are highly diverse in their sequences and structures. Most display broad range antimicrobial activity at low micromolar concentrations, whereas others have other diverse roles, including cell signalling (e.g. immune cell recruitment, self/non-self recognition), ion channel perturbation, toxic functions, and enzyme inhibition. The defensins consist of two superfamilies, each derived from an independent evolutionary origin, which have subsequently undergone extensive divergent evolution in their sequence, structure and function. Referred to as the cis- and trans-defensin superfamilies, they are classified based on their secondary structure orientation, cysteine motifs and disulphide bond connectivities, tertiary structure similarities and precursor gene sequence. The utility of displaying loops on a stable, compact, disulphide-rich core has been exploited by evolution on multiple occasions. The defensin superfamilies represent a case where the ensuing convergent evolution of sequence, structure and function has been particularly extreme. Here, we discuss the extent, causes and significance of these convergent features, drawing examples from across the eukaryotes. PMID- 27557673 TI - Prospectives of Solid Self-microemulsifying Systems in Novel Drug Delivery. AB - BACKGROUND: More than 60% of the new drug molecules are lipophilic in nature. Low aqueous solubility and thus poor bioavailability is the main issue for these drugs for successful formulations into oral dosage form. Self-microemulsifying drug delivery systems (SMEDDS) have gained much attention. These are isotropic mixtures of different components (oil, surfactant and cosurfactant) that quickly disperse in gastrointestinal fluid yielding micro/nano-emulsions. These systems contain solubilized drug that is absorbed by lymphatic pathway along with other pathways like diffusion, collisional transfer, intracellular junctions, biliary acid pathway (BA), biliary acid mixed micelles pathway (BAMM) etc. and thus hepatic first pass metabolism is reduced. Stability of conventional SEDDS is considered very high with reference to other drug delivery systems as liposome, nanoparticles, nanoemulsion and micro emulsion. In fact SEDDS does not contain water in their composition which enhances their chemical and physical stability. Very few works have studied the stability of conventional SEDDS as it was confirmed. The major drawback for conventional SEDDS could be- i) high manufacturing cost (as they have to be filled in soft gelatin capsules); ii) interaction of capsule shell components with SEDDS. Therefore, attention has been given to transform liquid into solid SMEDDS by several techniques such as spray drying, spray cooling, super critical fluid technology and using adsorption carriers. Adsorption using solid carriers (Neusilin, Fujicalin, and dextran) is the successful inexpensive technique at initial research level whereas other requires expensive instrumentation. CONCLUSION: Current review focuses on biopharmaceutical aspects, characterization of SMEDDS and excipients used in the formulation, techniques used for conversion of liquid SMEDDS to solid SMEDDS (including examples of various research reports where these techniques are used). Various adsorbent carriers (alongwith their different features) which have been reported in research papers have been detailed. It thoroughly covers patent literature on SMEDDS and research carried on solid SMEDDS as well which is the most imperative part of the review. PMID- 27557674 TI - The Experimental Demonstration of the Optimized Electrical Probe Memory for Ultra High Density Recording. AB - BACKGROUND: A theoretical model has been previously proposed to optimize the structure of the electrical probe memory system, whereby the optimal thickness and resistivity of DLC capping layer and TiN under layer are predicted to be 2 nm, 0.01 Ωm, and 40 nm, 2*10-7 Ωm,respectively However, there is no experimental evidence to show that such a media stack can be fabricated in reality by the time of writing and few patents regarding this intriguing topic have been reviewed and cited. METHODS: In order to realize this optimized design experimentally, the thickness dependent resistivity for both DLC and TiN film are assessed, from which it is not possible to obtain a media stack with exactly the same properties as the optimized design. Therefore, the previously proposed architecture is re-optimized using the measured properties values, and the capability of using the modified memory architecture to provide ultra-high density, high data rate, and low energy consumption is demonstrated. RESULTS: The results show that it is difficult to experimentally attain an electrical probe memory with exactly the same properties values as the optimized counterpart. CONCLUSIONS: An optimized electrical probe memory structure that includes a DLC capping layer and TiN under layer was previously proposed according to a parametric approach, while the practicality of realizing such a media stack experimentally has not bee investigated. In order to assess its practical feasibility, we first measured the electrical resistivities of DLC and TiN films for different thicknesses. In this case, for the purpose of optimizing the memory system with appropriate, but more physically realistic properties values, we re designed the architecture using the measured properties, and the modified system is able to provide ultra-high density, large data rate, and low energy consumption. PMID- 27557675 TI - AND Gate Response in a Double Mesoscopic Ring. AB - BACKGROUND: Normal metal mesoscopic rings are being used in designing quantum logical gates due to the quantum interference effect and quantum confinement. This study focused on examining electronic transport through normal metal mesoscopic rings that have one dimension, and suggested how such rings can be employed to design nanoscale AND gate. A double mesoscopic ring was utilized for AND gate operation, every ring was threaded by magnetic flux, and the magnetic flux was considered as the key tuning parameter in the AND gate action. For a particular value of magnetic flux equal to the half of elementary flux-quantum, a logical AND gate operation was used depending on the applied gate voltages. Two gate voltages were externally applied to the lower arm of every ring, which acted as the two inputs of the AND gate. Few relevant patents to the designing and fabrication of quantum logical gates have been reviewed and cited. METHODS: All the calculations are based on the time-dependent Hamiltonian model, the steady state is used to obtain the transmission probability. RESULTS: The transmission probability, the current and the noise power of current fluctuations were calculated in the weak-coupling and strong-coupling regimes. CONCLUSION: This study paved the way for the production of an electronic logic gate. PMID- 27557676 TI - Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives. AB - BACKGROUND: Intention-to-treat (ITT) analysis is commonly recommended for use, due to its benefits on external validity, in randomized, controlled trials (RCTs). No published reports describe how ITT analysis, as well as alternative approaches, are used in anti-infective RCTs. The purpose of this study is to describe the extent to which ITT analysis and alternative data approaches are used, the practices used to handle missing subject data, and whether non inferiority trials present both ITT and per protocol (PP) analyses. Results of this analysis will help guide end users of infectious diseases primary drug literature. METHODS: A cross-sectional study of RCTs of anti-infectives published from January 1, 2013 through December 31, 2014 was conducted. A PubMed search identified relevant articles published in five specialty infectious diseases journals and four general medical journals. Each article was reviewed by two independent investigators with discrepancies resolved by consensus. Descriptive statistics were used to quantify results. RESULTS: One hundred four articles met study criteria. The most common medication classes represented in the RCTs were hepatitis C antivirals (26 %), antibacterials (25 %), and antiretrovirals (21 %). Thirty studies (29 %) were non-inferiority trials. Most studies (77 %) described use of ITT or modified ITT (mITT) in their methods. Of the ITT and mITT studies, most (73 %) did not describe practices used to handle missing data. Most (97 %) non-inferiority trials described use of ITT, mITT, or both; however, only 15 (50 %) also described use of PP. CONCLUSIONS: RCTs of anti-infectives commonly employ ITT and mITT. Most do not describe how missing data were addressed. Non inferiority trials of anti-infectives do not consistently employ both ITT and PP populations. PMID- 27557677 TI - Application of receiver operating characteristic curve in the assessment of the value of body mass index, waist circumference and percentage of body fat in the Diagnosis of Polycystic Ovary Syndrome in childbearing women. AB - BACKGROUND: There are various parameters to analyze obesity, however, no standard reference to predict, screen or diagnose PCOS with various obesity parameters has been established, and the accuracy of these parameters still needs to be studied.This study was to use the receiver operating characteristic (ROC) curve to explore the different values of three obesity parameters, body mass index (BMI), waist circumference (WC) and percentage of body fat (PBF) in the diagnosis of polycystic ovary syndrome (PCOS) in Chinese childbearing women. METHODS: Three hundred patients who were diagnosed with PCOS at Center of Reproductive Medicine and Genetics of Peking University First Hospital were enrolled in this study, and 110 healthy age-matched women were enrolled as controls. The characteristics of BMI, WC and PBF in PCOS patients were analyzed. RESULTS: Compared with the control group, all the three obesity parameters were significantly increased in PCOS group. In terms of ROC area under the curve, WC > PBF > BMI, and they were all significantly different from those of the control. At a cut-off point of 80.5 cm, WC has a sensitivity of 73.6 % and a specificity of 85 % in diagnosis of PCOS; At a cut-off point of 29 %, PBF has a sensitivity of 88.2 % and a specificity of 57.7 % in diagnosis of PCOS; and at a cut-off point of 26.6 kg/m(2), BMI has a sensitivity of 54.5 % and a specificity of 98 % in diagnosis of PCOS. CONCLUSION: WC, BMI and PBF are valuable in screening and diagnosis of PCOS in Chinese childbearing women. PBF can be used to screen PCOS as it has a better sensitivity, while BMI can be used in the diagnosis of PCOS as it has a better specificity. PMID- 27557679 TI - Late infectious endocarditis of surgical patch closure of atrial septal defects diagnosed by 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG PET/CT): a case report. AB - BACKGROUND: In contrast to percutaneous atrial septal occluder device, surgical patch closure of atrial defects was known to be no infective endocarditis risk. CASE PRESENTATION: We herein report the first case of late endocarditis of surgical patch closure of atrial septal defects occurred at 47-year after surgery. On September 2014, a 56-year-old immunocompetent French Caucasian man was admitted into the Emergency Department for 3-week history of headache, acute decrease of psychomotor performance and fever at 40 degrees C. The diagnosis has been evoked during his admission for the management of a brain abscess and confirmed using 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG PET/CT). Bacterial cultures of surgical deep samples of brain abscess were positive for Streptococcus intermedius and Aggregatibacter aphrophilus as identified by the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and confirmed with 16S rRNA gene sequencing. The patient was treated by antibiotics for 8 weeks and surgical patch closure removal. CONCLUSIONS: In summary, late endocarditis on surgical patch and on percutaneous atrial septal occluder device of atrial septal defects is rare. Cardiac imaging by the 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT) could improve the diagnosis and care endocarditis on surgical patch closure of atrial septal defects while transthoracic and transesophageal echocardiography remained difficult to interpret. PMID- 27557678 TI - Electronic health records to facilitate clinical research. AB - Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research. PMID- 27557680 TI - Psychosocial Factors Associated with Alcohol Use Among Hispanic Youth. AB - This study examined whether authoritarian parenting, school experiences, depression, legal involvement and social norms predicted recent alcohol use and binge drinking among a national sample of Hispanic youth. A secondary data analysis of the National Survey on Drug Use and Health was performed (N = 3457). Unadjusted odds ratios were computed via univariate logistic regression analyses and significant variables were retained and included in the multivariable logistic regression analyses. Results indicated that in the past 30 days, 13.8 % of Hispanic youth drank alcohol and 8.0 % binge drank. Hispanic youth at highest risk for alcohol use were 16-17 years of age, experienced authoritarian parenting, lacked positive school experiences, had legal problems, and felt that most students at their school drank alcohol. Results should be considered when developing and implementing alcohol prevention efforts for Hispanic youth. Multiple approaches integrating family, school, and peers are needed to reduce use. PMID- 27557682 TI - Production of Engineered Minichromosome Vectors via the Introduction of Telomere Sequences. AB - Artificial minichromosomes are non-integrating vectors capable of stably maintaining transgenes outside of the main chromosome set. The production of minichromosomes relies on telomere-mediated chromosomal truncation, which involves introducing transgenes and telomere sequences concurrently to the cell to truncate an endogenous chromosomal target. Two methods can be utilized; either the telomere sequences can be incorporated into a binary vector for transformation with Agrobacterium tumefaciens, or the telomere sequences can be co-introduced with transgenes during particle bombardment. In this protocol, the methods required to isolate and introduce telomere sequences are presented. Following the methods presented, standard transformation procedures can be followed to produce minichromosome containing plants. PMID- 27557681 TI - Comparing Pregnancy Outcomes of Immigrants from Ethiopia and the Former Soviet Union to Israel, to those of Native-Born Israelis. AB - To compare pregnancy outcomes of immigrants from Former-Soviet-Union (FSUI) and Ethiopia (EI) to those of Jewish-native-born Israelis (JNB), in context of universal health insurance. Birth outcomes of all singletons born in Soroka University Medical-Center (1998-2011) of EI (n = 1,667) and FSUI (n = 12,920) were compared with those of JNB (n = 63,405). Low birthweight rate was significantly higher among EI (11.0 %) and slightly lower (7.0 %) among FSUI, compared to JNB (7.5 %). Preterm-delivery rates were similar to those of JNB. Both immigrant groups had significantly (p < 0.001) higher rates of perinatal mortality (PM) than JNB (21/1000 in EI, and 11/1000 in FSUI, compared to 9/1000). Using multivariable GEE models both immigrant groups had significantly increased risk for PM; however, EI had twice as much FSUI origin (OR 2.3, 95 % CI 1.6-3.4, and OR 1.3, 95 % CI 1.1-1.6, respectively). Universal health care insurance does not eliminate excess PM in immigrants, nor the gaps between immigrant groups. PMID- 27557683 TI - Method for Biolistic Site-Specific Integration in Plants Catalyzed by Bxb1 Integrase. AB - Crop improvement is a never ending process. With a transgenesis approach, it is not inconceivable to envision a continuous addition of new transgenes to existing cultivars. Previously, we described a recombinase-directed gene stacking method in tobacco (Hou et al., Mol Plant 7:1756-1765, 2014). Being able to stack DNA to a previous location ensures that the number of genetic loci does not increase with each new round of transgene addition. Whereas the previous demonstration was conducted through polyethylene glycol to mediate uptake of DNA into tobacco protoplasts, we now describe protocols for using biolistic transformation to stack DNA in tobacco and rice. PMID- 27557684 TI - Protocol for In Vitro Stacked Molecules Compatible with In Vivo Recombinase Mediated Gene Stacking. AB - Previously, we described a method for a recombinase-directed stacking of new DNA to an existing transgenic locus. Here, we describe how we can similarly stack DNA molecules in vitro and that the in vitro derived gene stack can be incorporated into an Agrobacterium transformation vector by in vitro recombination. After transfer to the chromosome by Agroinfection, the transgenic locus harbors a new target site that can be used for the subsequent in vivo stacking of new DNA. Alternatively, the in vitro derived gene stack has the potential to be integrated directly into the plant genome in vivo at a preexisting chromosomal target. Being able to stack DNA in vitro as well as in vivo, and with compatibility between the two systems, brings new flexibility for using the recombinase-mediated approach for transgene stacking. PMID- 27557685 TI - Generation and Analysis of Transposon Ac/Ds-Induced Chromosomal Rearrangements in Rice Plants. AB - Closely-located transposable elements (TEs) have been known to induce chromosomal breakage and rearrangements via alternative transposition. To study genome rearrangements in rice, an Ac/Ds system has been employed. This system comprises an immobile Ac element expressed under the control of CaMV 35S promoter, and a modified Ds element. A starter line carried Ac and a single copy of Ds at the OsRLG5 (Oryza sativa receptor-like gene 5). To enhance the transpositional activity, seed-derived calli were cultured and regenerated into plants. Among 270 lines regenerated from the starter, one line was selected that contained a pair of inversely-oriented Ds elements at the OsRLG5 (Oryza sativa receptor-like gene 5). The selected line was again subjected to tissue culture to obtain a regenerant population. Among 300 regenerated plants, 107 (36 %) contained chromosomal rearrangements including deletions, duplications, and inversions of various sizes. From 34 plants, transposition mechanisms leading to such genomic rearrangements were analyzed. The rearrangements were induced by sister chromatid transposition (SCT), homologous recombination (HR), and single chromatid transposition (SLCT). Among them, 22 events (65 %) were found to be transmitted to the next generation. These results demonstrate a great potential of tissue culture regeneration and the Ac/Ds system in understanding alternative transposition mechanisms and in developing chromosome engineering in plants. PMID- 27557686 TI - One-Step Generation of Chromosomal Rearrangements in Rice. AB - The combination of the DNA sequence-specific recombination system Cre/LoxP and the DNA transposon system Activator (Ac)/Dissociation (Ds) has been used for insertional and deletional mutagenesis, as well as for the generation of artificial ring chromosomes in model plants such as Arabidopsis and tobacco. However, it takes a long time to complete this process, even in Arabidopsis. To overcome this issue, a new binary vector, pDLHC, has been developed to induce chromosomal rearrangements for a short time in rice. pDLHC has been found to be effective in the induction of deletions between two LoxPs in the T2 generation of "Nihon bare" expressing Ac TPase. pDLHC has potential for the efficient generation of various types of chromosomal rearrangements including deletions, inversions, translocations and artificial ring chromosomes in plants, and the detailed protocol for rice is described here. PMID- 27557687 TI - Genome Elimination by Tailswap CenH3: In Vivo Haploid Production in Arabidopsis thaliana. AB - Artificial production of haploids is one of the important sought-after goals of plant breeding and crop improvement programs. Conventionally, haploid plants are generated by in vitro (tissue) culture of haploid plant gametophytes, pollen (male), and embryo sac (female). Here, we describe a facile, nontissue culture based in vivo method of haploid production through seeds in the model plant, Arabidopsis thaliana. This method involves simple crossing of any desired genotype of interest to a haploid-inducing strain (GFP-tailswap) to directly obtain haploid F1 seeds. The described protocol can be practiced by anyone with basic experience in growing A. thaliana plants and will be of interest to Arabidopsis research community. PMID- 27557688 TI - Gametocidal System for Dissecting Wheat Chromosomes. AB - Gametocidal (Gc) system is a novel method of inducing chromosome mutations in wheat by using Gc genes of wheat-related species. Many deletion lines were efficiently produced by this system and used for physical mapping of genes and DNA markers. A large stocks with chromosome deletions in homozygous state as well as the lines with Gc genes are available in the gene bank of Japan (KOMUGI). In this chapter, I describe the method of inducing breakage in a target chromosome using lines with the Gc gene on chromosome 2C of Aegilops cylindrica (a wheat related wild species) and nullisomic-tetrasomics. PMID- 27557689 TI - CRISPR/Cas-Mediated Site-Specific Mutagenesis in Arabidopsis thaliana Using Cas9 Nucleases and Paired Nickases. AB - The CRISPR/Cas system has recently become the most important tool for genome engineering due to its simple architecture that allows for rapidly changing the target sequence and its applicability to organisms throughout all kingdoms of life. The need for an easy-to-use and reliable nuclease is especially high in plant research, as precise genome modifications are almost impossible to achieve by Agrobacterium-mediated transformation and the regeneration of plants from protoplast cultures is very labor intensive. Here, we describe the application of the Cas9 nuclease to Arabidopsis thaliana for the induction of heritable targeted mutations, which may also be used for other plant species. To cover the concern for off-target activity, we also describe the generation of stable mutants using paired Cas9 nickases. PMID- 27557690 TI - Targeted Mutagenesis in Rice Using TALENs and the CRISPR/Cas9 System. AB - Sequence-specific nucleases (SSNs), such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system, are powerful tools for understanding gene function and for developing novel traits in plants. In plant species for which transformation and regeneration systems using protoplasts are not yet established, direct delivery to nuclei of SSNs either in the form of RNA or protein is difficult. Thus, Agrobacterium-mediated transformation of SSN expression constructs in cultured cells is a practical means of delivering targeted mutagenesis in some plant species including rice. Because targeted mutagenesis occurs stochastically in transgenic cells and SSN-mediated targeted mutagenesis often leads to no selectable phenotype, identification of highly mutated cell lines is a critical step in obtaining regenerated plants with desired mutations. PMID- 27557691 TI - Seamless Genome Editing in Rice via Gene Targeting and Precise Marker Elimination. AB - Positive-negative selection using hygromycin phosphotransferase (hpt) and diphtheria toxin A-fragment (DT-A) as positive and negative selection markers, respectively, allows enrichment of cells harboring target genes modified via gene targeting (GT). We have developed a successful GT system employing positive negative selection and subsequent precise marker excision via the piggyBac transposon derived from the cabbage looper moth to introduce desired modifications into target genes in the rice genome. This approach could be applied to the precision genome editing of almost all endogenous genes throughout the genome, at least in rice. PMID- 27557692 TI - Development of Genome Engineering Tools from Plant-Specific PPR Proteins Using Animal Cultured Cells. AB - The pentatricopeptide repeat (PPR) motif is a sequence-specific RNA/DNA-binding module. Elucidation of the RNA/DNA recognition mechanism has enabled engineering of PPR motifs as new RNA/DNA manipulation tools in living cells, including for genome editing. However, the biochemical characteristics of PPR proteins remain unknown, mostly due to the instability and/or unfolding propensities of PPR proteins in heterologous expression systems such as bacteria and yeast. To overcome this issue, we constructed reporter systems using animal cultured cells. The cell-based system has highly attractive features for PPR engineering: robust eukaryotic gene expression; availability of various vectors, reagents, and antibodies; highly efficient DNA delivery ratio (>80 %); and rapid, high throughput data production. In this chapter, we introduce an example of such reporter systems: a PPR-based sequence-specific translational activation system. The cell-based reporter system can be applied to characterize plant genes of interested and to PPR engineering. PMID- 27557693 TI - Chromosomal Allocation of DNA Sequences in Wheat Using Flow-Sorted Chromosomes. AB - Flow cytometry enables chromosomes to be sorted into different groups based on their characteristics, such as relative DNA content and the presence of repetitive DNA sequences. Despite the recent progress in the analysis of plant genome organization and chromosome structure, there is a need for easy methods to assign DNA sequences to individual chromosomes. Here, we describe an easy way to allocate genes or DNA sequences to chromosomes in wheat using flow-sorted chromosomes combined with fluorescence in situ hybridization and PCR analyses. PMID- 27557694 TI - Image Analysis of DNA Fiber and Nucleus in Plants. AB - Advances in cytology have led to the application of a wide range of visualization methods in plant genome studies. Image analysis methods are indispensable tools where morphology, density, and color play important roles in the biological systems. Visualization and image analysis methods are useful techniques in the analyses of the detailed structure and function of extended DNA fibers (EDFs) and interphase nuclei. The EDF is the highest in the spatial resolving power to reveal genome structure and it can be used for physical mapping, especially for closely located genes and tandemly repeated sequences. One the other hand, analyzing nuclear DNA and proteins would reveal nuclear structure and functions. In this chapter, we describe the image analysis protocol for quantitatively analyzing different types of plant genome, EDFs and interphase nuclei. PMID- 27557695 TI - Detection of Transgenes on DNA Fibers. AB - Fluorescence in situ hybridization (FISH) was developed for detecting specific DNA sequences directly on mitotic or meiotic chromosomes. However, the resolution of FISH on chromosomes is limited by condensed structure of chromatin, and it is difficult to differentiate two target sites close to each other. To overcome this issue, the objects was changed to stretched DNA fibers, and this fiber FISH technique has now been used for revealing genome structure at molecular level. Hybridization and detection procedures of fiber FISH are common with FISH on chromosomes. Therefore, application of fiber FISH is not difficult for the researchers of some experience in ordinary FISH. DNA fibers can be released from nuclei fixed on glass slides using a detergent. The DNA fibers were shred in FISH procedure, and the resultant fragments became small bead-like shape. This makes FISH signals on DNA fibers a series of dots. The size of DNA in the dot is estimated to be approximately 1 kb, it corresponding to the resolution of fiber FISH. This makes it possible to analyze structures of transgenes on DNA fibers in detail. PMID- 27557696 TI - Three-Dimensional, Live-Cell Imaging of Chromatin Dynamics in Plant Nuclei Using Chromatin Tagging Systems. AB - In plants, chromatin dynamics spatiotemporally change in response to various environmental stimuli. However, little is known about chromatin dynamics in the nuclei of plants. Here, we introduce a three-dimensional, live-cell imaging method that can monitor chromatin dynamics in nuclei via a chromatin tagging system that can visualize specific genomic loci in living plant cells. The chromatin tagging system is based on a bacterial operator/repressor system in which the repressor is fused to fluorescent proteins. A recent refinement of promoters for the system solved the problem of gene silencing and abnormal pairing frequencies between operators. Using this system, we can detect the spatiotemporal dynamics of two homologous loci as two fluorescent signals within a nucleus and monitor the distance between homologous loci. These live-cell imaging methods will provide new insights into genome organization, development processes, and subnuclear responses to environmental stimuli in plants. PMID- 27557697 TI - Chromatin Immunoprecipitation for Detecting Epigenetic Marks on Plant Nucleosomes. AB - Due to high resolution and reproducibility, chromatin immunoprecipitation (ChIP) has been used as a standard tool to investigate epigenetic marks including modified histones and specific histone variants (e.g., centromere-specific histone H3, CENH3) in this decade. Here, I describe a sensitive and low background ChIP protocol for a wide range of plant species. PMID- 27557698 TI - Mapping of T-DNA and Ac/Ds by TAIL-PCR to Analyze Chromosomal Rearrangements. AB - Insertion mutagenesis using known DNA sequences such as T-DNA and transposons is an important tool for studies on gene function in plant sciences. The transposons Activator (Ac)/Dissociation (Ds) have been systematically used to manipulate plant chromosomes. For both of these applications, the recovery of genomic DNA sequences flanking the insertions is required to estimate the sizes and/or scales of the reconstituted chromosomes. In this chapter, we describe the protocols for thermal asymmetric interlaced PCR (TAIL-PCR) for isolation of genomic sequences flanking DNA inserts in plant genomes. PMID- 27557699 TI - Performance and health of Holstein calves fed different levels of milk fortified with symbiotic complex containing pre- and probiotics. AB - The objective of this study was to evaluate the performance and health of Holstein calves fed low or high milk supply (MSP) with or without symbiotic complex (SYM) supplementation, consisting of prebiotics, probiotics, and fibrolytic enzymes. Thirty-two Holstein calves with body weight (BW) of 34 +/- 7 kg were distributed in a randomized block design in a 2 * 2 factorial arrangement. Treatments consisted of low and high MSP: 10 % of BW from 1st to 8th weeks after birth (low) and 20 % BW from 1st and 2nd weeks after birth, 15 % BW for the 3rd and 4th weeks after birth, and 10 % BW from 5th and 8th weeks after birth (high). Solid ration was supplied in addition to milk. Intake, ADG, diet digestibility, and fecal consistency index were evaluated. Low and high MSP groups tended (P < 0.10) to differ in calf growth, final BW (69 vs. 73 kg), post weaning average weight gain (548 vs. 788 g/day), and final average weight gain (549 vs. 646 g/day) in low and high MSP calves, respectively. There was an interaction between MSP level and SYM on the digestibilities of dry matter (DM) and neutral detergent fiber (NDF) (P < 0.10). In the low MSP group, inclusion of SYM increased digestibility of DM (0.720 to 0.736 g/kg) and NDF (0.758 to 0.783 g/kg). The inclusion of SYM improved calf health (P < 0.10) with a fecal score of 0.31 compared to 0.42 without SYM. Milk-feeding level was an important factor in calf performance, while SYM supplementation improved diet digestibility and animal health. PMID- 27557700 TI - Effects of stocking density and daily feed withdrawal periods on the performance of broiler chickens in a semi-arid environment. AB - Unsexed Ross 308 broilers were raised under three stocking densities (30, 35, and 40 kg BW/m2) and three daily feed withdrawal periods (0, 8, and 12 h daily) during a 42-day production period. The effects of stocking density and feed withdrawal on growth performance and carcass characteristics were investigated. The feed intake of broilers raised at the stocking density of 30 kg BW/m2 was higher than those of broilers reared at 35 and 40 kg BW/m2, but broilers raised under the different stocking densities did not differ significantly in 42-day body weight, body weight gain, feed conversion ratio, and mortality rate. Forty two-day body weight, body weight gain, and feed intake were reduced as the duration of feed withdrawal increased, but feeding program affected neither feed conversion ratio nor mortality rate. There was a stocking density effect on thigh percentage while feeding program influenced breast, back, wing, neck, liver, gizzard, and heart percentages. There were stocking density * feed withdrawal interaction effects on feed intake during the starter and grower periods. It is suggested that for profitable broiler production in the tropics stocking density of 40 kg BW/m2 and daily feed withdrawal for 8 h from 7 to 35 days of age be considered. PMID- 27557701 TI - Performance of crossbred heifers in different step-down waste milk-feeding strategies. AB - The aim of this study was to evaluate the consumption, performance, feed efficiency, glucose concentration, and the cost per kilogram of weight gain of crossbred Holstein-Gyr heifers (n = 33) subjected to one of the three waste milk step-down strategies: 6L-30d/4L-60d/2L-90d (T1), 6L-45d/4L-60d/2L-90d (T2), and 8L-30d/6L-60d/3L-90d (T3). Heifers were weaned at the age of 91 days. Water and starter were provided ad libitum. The average waste milk intake was higher in T3 than in T1 and T2 strategies until 30 days and between 60 and 90 days. The starter intake did not differ among the strategies until 45 days, but it was higher in strategy T1 than in strategy T3 between 60 and 90 days. The waste milk step-down strategy did not influence the total dry matter intake, average daily gain, body weight, and feed efficiency. Glucose concentrations in plasma varied within a range that could be considered normal and were similar among the treatments. The average cost per kilogram of weight gain was the lowest in strategy T1 (US$3.0) compared to that in the other strategies (T2, US$3.2, and T3, US$3.6). The 6L-30d/4L-60d/2L-90d waste milk step-down strategy was the most effective, since it increased the starter intake, led to normal glucose concentrations in plasma, and caused similar weight gain compared with the other strategies; however, it had a lower cost per kilogram. PMID- 27557702 TI - Impact of udder and teat morphometry on udder health in Tharparkar cows under climatic condition of hot arid region of Thar Desert. AB - Prevention of subclinical mastitis (SCM) is an important tool for sustainable dairying and implementing higher production level in animals. The present investigation involved a total of 397 quarters of milk examination of 105 indigenous Tharparkar cows at Livestock Research Centre, Chandan located in the Jaisalmer district of Rajasthan in Thar Desert to study the impact of udder and teat morphometry on udder health. Udder health was examined by somatic cell count to check the status of subclinical mastitis while udder and teat morphometry of 90 udder and 386 quarters, i.e., udder shape and depth, teat end shape, teat length, and teat diameter were examined at individual animal level and quarter level. Data were collected from the record register maintained at the farm and data evaluated by parity (no. of lactation) and stage of lactation. On analysis of variance, result revealed the significantly (P < 0.05) higher incidence of SCM was for pendulous shape udder in respect of regular udder, as well as for inverted and flat teat end shape in respect of pointed teat end shape. Large teat length and upper depth animals had significantly (P < 0.05) more incidence of SCM as compared to small and medium teat length and udder depth group, respectively. Thick teat diameter group animals were significantly (P < 0.01) more prone to infection as compared to medium and thin teat diameter group animals. So, it can be concluded that selection for optimum udder and teat morphometry in breeding program may help to reduce susceptibility for intramammary infections in Tharparkar cows. Microbiological study of milk samples could be helpful in the nearby future for identification of subclinical mastitis. PMID- 27557703 TI - Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection. AB - CRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies. PMID- 27557704 TI - May Stakeholders be Involved in Design Without Informed Consent? The Case of Hidden Design. AB - Stakeholder involvement in design is desirable from both a practical and an ethical point of view. It is difficult to do well, however, and some problems recur again and again, both of a practical nature, e.g. stakeholders acting strategically rather than openly, and of an ethical nature, e.g. power imbalances unduly affecting the outcome of the process. Hidden Design has been proposed as a method to deal with the practical problems of stakeholder involvement. It aims to do so by taking the observation of stakeholder actions, rather than the outcomes of a deliberative process, as its input. Furthermore, it hides from stakeholders the fact that a design process is taking place so that they will not behave differently than they otherwise would. Both aspects of Hidden Design have raised ethical worries. In this paper I make an ethical analysis of what it means for a design process to leave participants uninformed or deceived rather than acquiring their informed consent beforehand, and to use observation of actions rather than deliberation as input for design, using Hidden Design as a case study. This analysis is based on two sets of normative guidelines: the ethical guidelines for psychological research involving deception or uninformed participants from two professional psychological organisations, and Habermasian norms for a fair and just (deliberative) process. It supports the conclusion that stakeholder involvement in design organised in this way can be ethically acceptable, though under a number of conditions and constraints. PMID- 27557705 TI - Brief case management versus usual care for frequent users of emergency departments: the Coordinated Access to Care from Hospital Emergency Departments (CATCH-ED) randomized controlled trial. AB - BACKGROUND: Frequent users of hospital emergency departments (EDs) are a medically and socially vulnerable population. This article describes the rationale for a brief case management intervention for frequent ED users with mental health and/or addiction challenges and the design of a randomized trial assessing its effectiveness. METHODS/DESIGN: Eligible participants are adults in a large urban centre with five or more ED visits in the past year, with at least one prior visit for a mental health or addictions reason. Participants (N = 166) will be randomized to either 4 to 6 months of brief case management or usual care, and interviewed every 3 months for 1 year. Consent will be sought to access administrative health records. A subset of participants (N = 20) and service providers (N = 13) will participate in qualitative data collection. DISCUSSION: Addressing the needs of frequent ED users is a priority in many jurisdictions. This study will provide evidence on the effectiveness of brief case management, compared to usual care, on reducing ED visits among frequent ED users experiencing mental health or substance misuse problems, and inform policy and practice in this important area. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01622244 . Registered 4 June 2012. PMID- 27557706 TI - Many Inflammatory Bowel Disease Patients Are Not Immune to Measles or Pertussis. AB - BACKGROUND: Current guidelines emphasize vaccination for influenza and pneumococcus for IBD patients and the avoidance of live virus vaccines for those who are on immunosuppressive (ISS) therapy. Given the recent resurgence of measles and pertussis infections, we assessed the immune status of our IBD population in order to advise about these risks. METHODS: We prospectively collected measles and pertussis titers in our IBD patients from February 1-May 1, 2015. Immune status based on standard threshold values was determined: measles antibodies <=0.8 antibody index (AI) = negative immunity, 0.9-1.1 AI = equivocal immunity and titers >=1.2 AI = positive immunity. For pertussis immunity, anti pertussis antibodies <=5 IU/mL were considered negative immunity. Univariate analysis was performed to examine predictive factors including age, disease duration, and current medical therapies. RESULTS: A total of 122 patients' titers were assessed (77 Crohn's disease, 1 indeterminate colitis, and 45 ulcerative colitis). Sixteen (13.1 %) patients lacked detectable immunity to measles, and four (3 %) had equivocal immunity. Twelve (75 %) of the measles non-immune patients were on ISS therapy versus 65 (64 %) of 102 immune patients (OR 1.7, 95 % CI 0.5-5.9, p = 0.34). Out of 96 patients, 58 (60 %) were not immune to pertussis. Disease duration >=10 years and age >=50 were associated with significant lower measles titers. CONCLUSIONS: A significant number of our IBD patients lack immunity to measles, and a majority of our IBD patients do not have detectable immunity to pertussis. Importantly, the majority of the measles non immune patients are on ISS therapy and therefore unable to receive a booster. PMID- 27557707 TI - Conservation of context-dependent splicing activity in distant Muscleblind homologs. AB - The Muscleblind (MBL) protein family is a deeply conserved family of RNA binding proteins that regulate alternative splicing, alternative polyadenylation, RNA stability and RNA localization. Their inactivation due to sequestration by expanded CUG repeats causes symptoms in the neuromuscular disease myotonic dystrophy. MBL zinc fingers are the most highly conserved portion of these proteins, and directly interact with RNA. We identified putative MBL homologs in Ciona intestinalis and Trichoplax adhaerens, and investigated their ability, as well as that of MBL homologs from human/mouse, fly and worm, to regulate alternative splicing. We found that all homologs can regulate alternative splicing in mouse cells, with some regulating over 100 events. The cis-elements through which each homolog exerts its splicing activities are likely to be highly similar to mammalian Muscleblind-like proteins (MBNLs), as suggested by motif analyses and the ability of expanded CUG repeats to inactivate homolog-mediated splicing. While regulation of specific target exons by MBL/MBNL has not been broadly conserved across these species, genes enriched for MBL/MBNL binding sites in their introns may play roles in cell adhesion, ion transport and axon guidance, among other biological pathways, suggesting a specific, conserved role for these proteins across a broad range of metazoan species. PMID- 27557708 TI - Analysis of C. elegans muscle transcriptome using trans-splicing-based RNA tagging (SRT). AB - Current approaches to profiling tissue-specific gene expression in C. elegans require delicate manipulation and are difficult under certain conditions, e.g. from dauer or aging worms. We have developed an easy and robust method for tissue specific RNA-seq by taking advantage of the endogenous trans-splicing process. In this method, transgenic worms are generated in which a spliced leader (SL) RNA gene is fused with a sequence tag and driven by a tissue-specific promoter. Only in the tissue of interest, the tagged SL RNA gene is transcribed and then trans spliced onto mRNAs. The tag allows enrichment and sequencing of mRNAs from that tissue only. As a proof of principle, we profiled the muscle transcriptome, which showed high coverage and efficient enrichment of muscle specific genes, with low background noise. To demonstrate the robustness of our method, we profiled muscle gene expression in dauer larvae and aging worms, revealing gene expression changes consistent with the physiology of these stages. The resulting muscle transcriptome also revealed 461 novel RNA transcripts, likely muscle-expressed long non-coding RNAs. In summary, the splicing-based RNA tagging (SRT) method provides a convenient and robust tool to profile trans-spliced genes and identify novel transcripts in a tissue-specific manner, with a low false positive rate. PMID- 27557709 TI - Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements. AB - Polycomb Group (PcG) proteins are epigenetic repressors essential for control of development and cell differentiation. They form multiple complexes of which PRC1 and PRC2 are evolutionary conserved and obligatory for repression. The targeting of PRC1 and PRC2 is poorly understood and was proposed to be hierarchical and involve tri-methylation of histone H3 (H3K27me3) and/or monoubiquitylation of histone H2A (H2AK118ub). Here, we present a strict test of this hypothesis using the Drosophila model. We discover that neither H3K27me3 nor H2AK118ub is required for targeting PRC complexes to Polycomb Response Elements (PREs). We find that PRC1 can bind PREs in the absence of PRC2 but at many PREs PRC2 requires PRC1 to be targeted. We show that one role of H3K27me3 is to allow PcG complexes anchored at PREs to interact with surrounding chromatin. In contrast, the bulk of H2AK118ub is unrelated to PcG repression. These findings radically change our view of how PcG repression is targeted and suggest that PRC1 and PRC2 can communicate independently of histone modifications. PMID- 27557710 TI - An efficient system for selectively altering genetic information within mRNAs. AB - Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encoded iteration of SDRE could target adenosines expressed in human cells, but not efficiently. Here we developed a reporter assay to quantify editing, and used it to improve our strategy. By enhancing the linkage between ADAR's catalytic domain and the guide RNA, and by introducing a mutation in the catalytic domain, the efficiency of converting a U A: G premature termination codon (PTC) to tryptophan (U G: G) was improved from ~11 % to ~70 %. Other PTCs were edited, but less efficiently. Numerous off-target edits were identified in the targeted mRNA, but not in randomly selected endogenous messages. Off-target edits could be eliminated by reducing the amount of guide RNA with a reduction in on-target editing. The catalytic rate of SDRE was compared with those for human ADARs on various substrates and found to be within an order of magnitude of most. These data underscore the promise of site-directed RNA editing as a therapeutic or experimental tool. PMID- 27557713 TI - Diagnostic Value of Right Ventricular Dysfunction in Tachycardia-Induced Cardiomyopathy Using Cardiac Magnetic Resonance Imaging. AB - BACKGROUND: Predicting tachycardia-induced cardiomyopathy (TIC) in patients presenting with left ventricular (LV) dysfunction and tachyarrhythmias remains challenging. We assessed the diagnostic value of early right ventricular (RV) dysfunction to predict TIC using cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS: A total of 102 consecutive patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias were examined. Patients whose LV ejection fraction (EF) improved to >=50% during a 1-year follow-up were diagnosed with TIC, and with dilated cardiomyopathy (DCM) in those whose did not improve. CMR was performed at a median of 23 days after admission, and the TIC and DCM patients exhibited different distributions of EF and end-diastolic volume (EDV) between the LV and RV (both P<0.001, ANCOVA). TIC patients had significantly lower RVEF/LVEF ratio (1.01+/-0.23 vs. 1.36+/-0.31, P<0.001) and higher RVEDV/LVEDV ratio (0.96+/-0.21 vs. 0.73+/-0.19, P<0.001) compared with DCM patients, suggesting that RV systolic dysfunction and RV dilatation were observed in TIC. In the multivariate analysis, age, RVEF/LVEF ratio, and RVEDV/LVEDV ratio were significant predictors of TIC, and RVEF/LVEF ratio of <1.05 most highly predicted TIC with a sensitivity of 69.1% and specificity of 91.5% (area under the curve 0.860). CONCLUSIONS: Among patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias, age and coexistence of RV dysfunction was a strong predictor of TIC. (Circ J 2016; 80: 2141-2148). PMID- 27557711 TI - RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns. AB - Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by insufficient levels of the Survival of Motor Neuron (SMN) protein. SMN is expressed ubiquitously and functions in RNA processing pathways that include trafficking of mRNA and assembly of snRNP complexes. Importantly, SMA severity is correlated with decreased snRNP assembly activity. In particular, the minor spliceosomal snRNPs are affected, and some U12-dependent introns have been reported to be aberrantly spliced in patient cells and animal models. SMA is characterized by loss of motor neurons, but the underlying mechanism is largely unknown. It is likely that aberrant splicing of genes expressed in motor neurons is involved in SMA pathogenesis, but increasing evidence indicates that pathologies also exist in other tissues. We present here a comprehensive RNA-seq study that covers multiple tissues in an SMA mouse model. We show elevated U12-intron retention in all examined tissues from SMA mice, and that U12-dependent intron retention is induced upon siRNA knock-down of SMN in HeLa cells. Furthermore, we show that retention of U12-dependent introns is mitigated by ASO treatment of SMA mice and that many transcriptional changes are reversed. Finally, we report on missplicing of several Ca2+ channel genes that may explain disrupted Ca2+ homeostasis in SMA and activation of Cdk5. PMID- 27557712 TI - DNA gyrase with a single catalytic tyrosine can catalyze DNA supercoiling by a nicking-closing mechanism. AB - The topological state of DNA is important for replication, recombination and transcription, and is regulated in vivo by DNA topoisomerases. Gyrase introduces negative supercoils into DNA at the expense of ATP hydrolysis. It is the accepted view that gyrase achieves supercoiling by a strand passage mechanism, in which double-stranded DNA is cleaved, and a second double-stranded segment is passed through the gap, converting a positive DNA node into a negative node. We show here that gyrase with only one catalytic tyrosine that cleaves a single strand of its DNA substrate can catalyze DNA supercoiling without strand passage. We propose an alternative mechanism for DNA supercoiling via nicking and closing of DNA that involves trapping, segregation and relaxation of two positive supercoils. In contrast to DNA supercoiling, ATP-dependent relaxation and decatenation of DNA by gyrase lacking the C-terminal domains require both tyrosines and strand passage. Our results point towards mechanistic plasticity of gyrase and might pave the way for finding novel and specific mechanism-based gyrase inhibitors. PMID- 27557715 TI - Directed chromosomal integration and expression of porcine rotavirus outer capsid protein VP4 in Lactobacillus casei ATCC393. AB - Using two-step plasmid integration in the presence of 5-fluorouracil (5-FU), we developed a stable and markerless Lactobacillus casei strain for vaccine antigen expression. The upp of L. casei, which encodes uracil phosphoribosyltransferase (UPRTase), was used as a counterselection marker. We employed the Deltaupp isogenic mutant, which is resistant to 5-FU, as host and a temperature-sensitive suicide plasmid bearing upp expression cassette as counterselectable integration vector. Extrachromosomal expression of UPRTase complemented the mutated chromosomal upp allele and restored sensitivity to 5-FU. The resultant genotype can either be wild type or recombinant. The efficacy of the system was demonstrated by insertion and expression of porcine rotavirus (PRV) VP4. To improve VP4 expression, we analyzed L. casei transcriptional profiles and selected the constitutive highly expressed enolase gene (eno). The VP4 inserted after the eno termination codon were screened in the presence of 5-FU. Using genomic PCR amplification, we confirmed that VP4 was successfully integrated and stably inherited for at least 50 generations. Western blot demonstrated that VP4 was steadily expressed in medium with different carbohydrates. RT-qPCR and ELISA analysis showed that VP4 expression from the chromosomal location was similar to that achieved by a plasmid expression system. Applying the recombinant strain to immunize BALB/c mice via oral administration revealed that the VP4-expressing L. casei could induce both specific local and systemic humoral immune responses in mice. Overall, the improved gene replacement system represents an efficient method for chromosome recombination in L. casei and provides a safe tool for vaccine production. PMID- 27557716 TI - Computational design of variants for cephalosporin C acylase from Pseudomonas strain N176 with improved stability and activity. AB - In this report, redesigning cephalosporin C acylase from the Pseudomonas strain N176 revealed that the loss of stability owing to the introduced mutations at the active site can be recovered by repacking the nearby hydrophobic core regions. Starting from a quadruple mutant M31betaF/H57betaS/V68betaA/H70betaS, whose decrease in stability is largely owing to the mutation V68betaA at the active site, we employed a computational enzyme design strategy that integrated design both at hydrophobic core regions for stability enhancement and at the active site for activity improvement. Single-point mutations L154betaF, Y167betaF, L180betaF and their combinations L154betaF/L180betaF and L154betaF/Y167betaF/L180betaF were found to display improved stability and activity. The two-point mutant L154betaF/L180betaF increased the protein melting temperature (T m) by 11.7 degrees C and the catalytic efficiency V max/K m by 57 % compared with the values of the starting quadruple mutant. The catalytic efficiency of the resulting sixfold mutant M31betaF/H57betaS/V68betaA/H70betaS/L154betaF/L180betaF is recovered to become comparable to that of the triple mutant M31betaF/H57betaS/H70betaS, but with a higher T m. Further experiments showed that single-point mutations L154betaF, L180betaF, and their combination contribute no stability enhancement to the triple mutant M31betaF/H57betaS/H70betaS. These results verify that the lost stability because of mutation V68betaA at the active site was recovered by introducing mutations L154betaF and L180betaF at hydrophobic core regions. Importantly, mutation V68betaA in the six-residue mutant provides more space to accommodate the bulky side chain of cephalosporin C, which could help in designing cephalosporin C acylase mutants with higher activities and the practical one-step enzymatic route to prepare 7-aminocephalosporanic acid at industrial-scale levels. PMID- 27557714 TI - Diversity and function of prevalent symbiotic marine bacteria in the genus Endozoicomonas. AB - Endozoicomonas bacteria are emerging as extremely diverse and flexible symbionts of numerous marine hosts inhabiting oceans worldwide. Their hosts range from simple invertebrate species, such as sponges and corals, to complex vertebrates, such as fish. Although widely distributed, the functional role of Endozoicomonas within their host microenvironment is not well understood. In this review, we provide a summary of the currently recognized hosts of Endozoicomonas and their global distribution. Next, the potential functional roles of Endozoicomonas, particularly in light of recent microscopic, genomic, and genetic analyses, are discussed. These analyses suggest that Endozoicomonas typically reside in aggregates within host tissues, have a free-living stage due to their large genome sizes, show signs of host and local adaptation, participate in host associated protein and carbohydrate transport and cycling, and harbour a high degree of genomic plasticity due to the large proportion of transposable elements residing in their genomes. This review will finish with a discussion on the methodological tools currently employed to study Endozoicomonas and host interactions and review future avenues for studying complex host-microbial symbioses. PMID- 27557717 TI - At-line determining spore germination of Penicillium chrysogenum bioprocesses in complex media. AB - Spore inoculum quality in filamentous bioprocesses is a critical parameter associated with viable spore concentration (1) and spore germination (2). It influences pellet morphology and, consequently, process performance. The state-of the-art method to measure viable spore concentration is tedious, associated with significant inherent bias, and not applicable in real-time. Therefore, it is not usable as process analytical technology (PAT). Spore germination has so far been monitored using image analysis, which is hampered by complex medium background often observed in filamentous bioprocesses. The method presented here is based on the combination of viability staining and large-particle flow cytometry which enables measurements in real-time and hence aims to be applicable as a PAT tool. It is compatible with the complex media background and allows the quantification of metabolically active spores and the monitoring of spore germination. A distinction of germinated spores and not germinated spores was based on logistic regression, using multiparameteric data from flow cytometry. In a first step, a significant correlation between colony-forming unit (CFU) counts and viable spore concentration (1) in an industrially relevant model bioprocess was found. Spore germination (2) was followed over the initial process phase with close temporal resolution. The validation of the method showed an error below 5 %. Differences in spore germination for various spore inocula ages and spore inoculum concentrations were monitored. The real-time applicability of the method suggests the implementation as a PAT tool in filamentous bioprocesses. PMID- 27557718 TI - Assessment of farm soil, biochar, compost and weathered pine mulch to mitigate methane emissions. AB - Previous studies have demonstrated the effective utility of volcanic pumice soil to mitigate both high and low levels of methane (CH4) emissions through the activity of both gamma-proteobacterial (type I) and alpha-proteobacterial (type II) aerobic methanotrophs. However, the limited availability of volcanic pumice soil necessitates the assessment of other farm soils and potentially suitable, economical and widely available biofilter materials. The potential biofilter materials, viz. farm soil (isolated from a dairy farm effluent pond bank area), pine biochar, garden waste compost and weathered pine bark mulch, were inoculated with a small amount of volcanic pumice soil. Simultaneously, a similar set-up of potential biofilter materials without inoculum was studied to understand the effect of the inoculum on the ability of these materials to oxidise CH4 and their effect on methanotroph growth and activity. These materials were incubated at 25 degrees C with periodic feeding of CH4, and flasks were aerated with air (O2) to support methanotroph growth and activity by maintaining aerobic conditions. The efficiency of CH4 removal was monitored over 6 months. All materials supported the growth and activity of methanotrophs. However, the efficiency of CH4 removal by all the materials tested fluctuated between no or low removal (0-40 %) and high removal phases (>90 %), indicating biological disturbances rather than physico-chemical changes. Among all the treatments, CH4 removal was consistently high (>80 %) in the inoculated farm soil and inoculated biochar, and these were more resilient to changes in the methanotroph community. The CH4 removal from inoculated farm soil and inoculated biochar was further enhanced (up to 99 %) by the addition of a nutrient solution. Our results showed that (i) farm soil and biochar can be used as a biofilter material by inoculating with an active methanotroph community, (ii) an abundant population of alpha-proteobacterial methanotrophs is essential for effective and stable CH4 removal and (iii) addition of nutrients enhances the growth and activity of methanotrophs in the biofilter materials. Further studies are underway to assess the feasibility of these materials at small plot and field scales. PMID- 27557720 TI - Screening, identification, and characterization of a novel saccharide-stimulated beta-glycosidase from a soil metagenomic library. AB - MeBglD2, a beta-glycosidase that is highly activated in the presence of various monosaccharides and disaccharides, was isolated from a soil metagenomic library. MeBglD2 had not only beta-glucosidase activity but also beta-galactosidase and beta-fucosidase activities. MeBglD2 beta-glucosidase activity increased in a cellobiose concentration-dependent manner and was not inhibited by a high concentration of D-glucose or cellobiose. MeBglD2 beta-glucosidase and beta fucosidase activities were activated by various monosaccharides and disaccharides including D-glucose, D-xylose, D-galactose, maltose, and cellobiose. The saccharification yield of rice straw using Trichoderma reesei cellulase was improved by the addition of MeBglD2. These results show that MeBglD2 can be used to improve plant biomass saccharification, because both substrates and products can activate its enzymatic activity. PMID- 27557719 TI - Cultivation and characteristics of partial nitrification granular sludge in a sequencing batch reactor inoculated with heterotrophic granules. AB - The aim of this study was to develop a simple operation strategy for the cultivation of partial nitrification granules (PNGs) treating an autotrophic medium. For this strategy, aerobic granular sludge adapted to high concentration organics removal was seeded in a sequencing batch reactor (SBR) with a height/diameter ratio of 3.8, and the ratio of organics to the ammonia nitrogen loading rate (C/N ratio) in the influent was employed as the main control parameter to start up the partial nitrification process. After 86 days of operation, the nitrite accumulation rate reached 1.44 kg/(m3 day) in the SBR, and the removal efficiency of ammonia nitrogen (NH4+-N) was over 95 %. The PNGs showed a dense and compact structure, with an excellent settling ability, a typical extracellular polymeric substance (EPS) composition, and a high ammonia oxidation activity. The high-throughput pyrosequencing results indicated that the microbial community structure in the granules was significantly influenced by the C/N ratio, and ammonia-oxidizing bacteria (AOB), including the r-strategist Nitrosomonas and k-strategist Nitrosospira genre, which accounted for approximately 40 % of the total biomass at the end of operation. The effective suppression of nitrite-oxidizing bacteria (NOB) growth was attributed to oxygen competition on the granular surface among functional bacteria, as well as the high free ammonia or free nitrous acid concentrations during the aeration period. PMID- 27557721 TI - Application of conditionally replicating adenoviruses in tumor early diagnosis technology, gene-radiation therapy and chemotherapy. AB - Conditionally replicating adenoviruses (CRAds), or known as replication-selective adenoviruses, were discovered as oncolytic gene vectors several years ago. They have a strong ability of scavenging tumor and lesser toxicity to normal tissue. CRAds not only have a tumor-killing ability but also can combine with gene therapy, radiotherapy, and chemotherapy to induce tumor cell apoptosis. In this paper, we review the structure of CRAds and CRAd vectors and summarize the current application of CRAds in tumor detection as well as in radiotherapy and suicide gene-mediating chemotherapy. We also propose further research strategies that can improve the application value of CRAds, including enhancing tumor destruction effect, further reducing toxic effect, reducing immunogenicity, constructing CRAds that can target tumor stem cells, and trying to use mesenchymal stem cells (MSCs) as the carriers for oncolytic adenoviruses. As their importance to cancer diagnosis, gene-radiation, and chemotherapy, CRAds may play a considerable role in clinical diagnosis and various cancer treatments in the future. PMID- 27557722 TI - Distinct distribution patterns of prokaryotes between sediment and water in the Yellow River estuary. AB - There are close exchanges between sediment and water in estuaries; however, the patterns of prokaryotic community assembly in these two habitat types are still unclear. This study investigated the bacterial and archaeal abundance, diversity, and community composition in the sediment and the overlying water of the Yellow River estuary. Notably higher prokaryotic abundance and diversity were detected in the sediment than in the water, and bacterial abundance and diversity were remarkably higher than those of archaea. Furthermore, the ratio of bacterial to archaeal 16S rRNA gene abundance was significantly lower in the sediment than in the water. Bacterial communities at different taxonomic levels were apparently distinct between the sediment and water, but archaeal communities were not. The most dominant bacteria were affiliated with Deltaproteobacteria and Gammaproteobacteria in sediment and with Alphaproteobacteria and Betaproteobacteria in water. Euryarchaeota and Thaumarchaeota were the most abundant archaea in both habitats. Although distinct prokaryotic distribution patterns were observed, most of the dominant bacteria and archaea present were related to carbon, nitrogen, and sulfur cycling processes, such as methanogenesis, ammonia oxidation, and sulfate reduction. Unexpectedly, prokaryotes from the water showed a higher sensitivity to environmental factors, while only a few factors affected sediment communities. Additionally, some potential co-occurrence relationships between prokaryotes were also found in this study. These results suggested distinct distribution patterns of bacterial and archaeal communities between sediment and overlying water in this important temperate estuary, which may serve as a useful community model for the further ecological and evolutionary study of prokaryotes in estuarine ecosystems. PMID- 27557723 TI - Directed evolution of mandelate racemase by a novel high-throughput screening method. AB - Optically pure methyl (R)-o-chloromandelate and (R)-acetyl-o-mandelic acid are key intermediates for the synthesis of (S)-clopidogrel, which could be prepared with 100 % theoretical yield by sequential hydrolysis and racemization. At the moment, efficient sequential hydrolysis and racemization are hindered by the low catalytic activity of mandelate racemase (MR) toward (S)-o-chloromandelic acid ((S)-2-CMA). In the present work, we proposed to improve the catalytic performance of MR toward (S)-2-CMA by directed evolution and developed an enantioselective oxidation system for high-throughput screening (HTS) of MR libraries. Based on this HTS method, a triple mutant V22I/V29I/Y54F (MRDE1) with 3.5-fold greater relative activity as compared to the native MR was obtained. Kinetic analysis indicated that the enhanced catalytic efficiency mainly arose from the elevated k cat. Further insight into the source of improved catalytic activity was gained by molecular simulations, finding that substrate binding and product release were possibly made easier by decreased steric bulk and increased hydrophobicity of substrate binding sites. In addition, the substrate (S)-2-CMA in the enzyme-substrate complex of MRDE1 seemed to have a lower binding free energy comparing with the complex of wild-type MR. The HTS method developed in this work and the successful directed evolution of MR based on this method provide an example for racemase engineering and may inspire directed evolution of other racemases toward enhanced catalytic performance on non-natural substrates. PMID- 27557724 TI - Abnormal gastric bleeding: please don't touch! PMID- 27557725 TI - Association between maternal depression and child stunting in Northern Ghana: a cross-sectional study. AB - BACKGROUND: Stunting indicates failure to attain genetic potential for height and is a well-documented indicator for poor growth. Depression is common in women of reproductive age and women's mental health problems may affect the growth of young children. We examined the association between maternal depression and stunting in mother-child pairs attending Child Welfare Clinic (CWC) in Northern Ghana. METHODS: An analytical cross-sectional study was performed involving mothers (15-45 years) and their children (0-59 months) who attended CWC at Bilpeila Health Centre, Tamale, Ghana. Socio-demographic data were collected using a semi-structured questionnaire, maternal depression was measured using Centre for Epidemiological Studies Depression Screening Scale, and anthropometry was conducted on children following standard procedures. The association between maternal depression and child stunting was examined in logistic regression adjusting for potential confounders. RESULTS: Prevalence rates of child stunting and maternal depression were estimated at 16.1 and 27.8 % respectively in Northern Ghana. Mothers with depression when compared with those without depression tended to be younger, be currently unmarried, belong to the poorest household wealth tertile, and were more likely to have low birth weight babies, so these characteristics were adjusted for. In an adjusted multivariate logistic regression model, children of depressed mothers were almost three times more likely to be stunted compared to children of non-depressed mothers (Adjusted OR = 2.48, 95 % CI 1.29-4.77, p = 0.0011). CONCLUSIONS: There is a high prevalence of depression among mothers in Northern Ghana which is associated with child stunting. Further studies are needed to identify the determinants of maternal depression and to examine its association with child stunting to inform nutrition programming. PMID- 27557726 TI - Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury. AB - The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100-150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI. PMID- 27557727 TI - Pregnancy outcomes in liver transplant recipients: A 15-year single-center experience. AB - AIM: There are an increasing number of reports of pregnancy following liver transplantation, but many questions remain regarding preconception counseling and management of the pregnancy. The aim of this study was to report pregnancy outcomes in women who had undergone liver transplants and to gain insight into these issues. METHODS: We conducted a retrospective review of liver transplant recipients who had received prenatal care at Kyoto University Hospital between January 2001 and December 2015. RESULTS: Twenty-six consecutive pregnancies in 17 liver transplant recipients were identified during the period. The most common indication for liver transplantation was biliary atresia (65%). The median age at transplantation was 19 years (range, 2-38). The median age at conception was 28 years (range, 20-41) with a median time between transplantation and conception of 8 years (range, 0-22). A tacrolimus-based immunosuppressive regimen (n = 21, 81%) was the most common at the time of conception. There were 13 live births (50%), four spontaneous miscarriages (15%), and nine induced abortions (35%). Median gestational age at delivery was 38 weeks (range, 32-42), and the median birthweight was 2858 g (range, 1815-3864 g). Pregnancy and maternal complications included preterm deliveries (23%), intrauterine growth restriction (23%), pre eclampsia (8%), cesarean delivery (23%), bacterial infection (15%), and biopsy proven acute cellular rejection (15%). Two infants had congenital anomalies (tetralogy of Fallot and hydronephrosis). CONCLUSION: Pregnancy after liver transplantation can achieve relatively favorable outcomes. Obstetricians should be involved in the contraceptive and fertility counseling of female transplant recipients to prevent unintended pregnancies. PMID- 27557729 TI - Chapter 7 - After treatment. PMID- 27557730 TI - Engineering Corynebacterium glutamicum for violacein hyper production. AB - BACKGROUND: Corynebacterium glutamicum was used as a metabolic engineering chassis for production of crude violacein (mixture of violacein and deoxyviolacein) due to Corynebacterium's GRAS status and advantages in tryptophan fermentation. The violacein is a commercially potential compound with various applications derived from L-tryptophan. RESULTS: Corynebacterium glutamicum ATCC 21850 that could produce 162.98 mg L(-1) tryptophan was employed as a novel host for metabolic engineering chassis. Heterologous vio operon from Chromobacterium violaceum was over-expressed in ATCC 21850 strain with constitutive promoter to have obtained 532 mg L(-1) violacein. Considering toxicity of violacein, vio operon was expressed with inducible promoter and 629 mg L(-1) violacein was obtained in batch culture. Due to the economical coding nature of vio operon, the compressed RBS of vio genes were replaced with complete strong C. glutamicum ones. And extended expression units were assembled to form a synthetic operon. With this strategy, 1116 mg L(-1) violacein in batch culture was achieved. Fermentation process was then optimized by studying induction time, induction concentration, culture composition and fermentation temperature. as a result, a titer of 5436 mg L(-1) and a productivity of 47 mg L(-1) h(-1) were achieved in 3 L bioreactor. CONCLUSIONS: With metabolic engineering and fermentation optimization practice, C. glutamicum 21850 (pEC-C-vio1) was able to produce violacein with both titer and productivity at the highest level ever reported. Due to advantages of mature C. glutamicum fermentation industry, this work has built basis for commercial production of violacein. PMID- 27557731 TI - Spatial patterns of self-recruitment of a coral reef fish in relation to island scale retention mechanisms. AB - Oceanographic features influence the transport and delivery of marine larvae, and physical retention mechanisms, such as eddies, can enhance self-recruitment (i.e. the return of larvae to their natal population). Knowledge of exact locations of hatching (origin) and settlement (arrival) of larvae of reef animals provides a means to compare observed patterns of self-recruitment 'connectivity' with those expected from water circulation patterns. Using parentage inference based on multiple sampling years in Moorea, French Polynesia, we describe spatial and temporal variation in self-recruitment of the anemonefish Amphiprion chrysopterus, evaluate the consistency of net dispersal distances of self recruits against the null expectation of passive particle dispersal and test the hypothesis that larvae originating in certain reef habitats (lagoons and passes) would be retained and thus more likely to self-recruit than those originating on the outer (fore) reef. Estimates of known self-recruitment were consistent across the sampling years (~25-27% of sampled recruits). For most (88%) of these self recruits, the net distance between hatching and settlement locations was within the maximum dispersal distance expected for a neutrally buoyant passive particle based on the longest duration of the larval dispersive phase and the average direction and speed of current flow around Moorea. Furthermore, a parent of a given body size on the outer (fore) reef of Moorea was less likely to produce self-recruits than those in passes. Our findings show that even a simple dispersal model based on net average flow and direction of alongshore currents can provide insight into landscape-scale retention patterns of reef fishes. PMID- 27557733 TI - Chronic undiagnosed orbital inflammation due to factitious disorder: a 'think different' paradigm. PMID- 27557732 TI - Universal shape and pressure inside bubbles appearing in van der Waals heterostructures. AB - Trapped substances between a two-dimensional (2D) crystal and an atomically flat substrate lead to the formation of bubbles. Their size, shape and internal pressure are determined by the competition between van der Waals attraction of the crystal to the substrate and the elastic energy needed to deform it, allowing to use bubbles to study elastic properties of 2D crystals and conditions of confinement. Using atomic force microscopy, we analysed a variety of bubbles formed by monolayers of graphene, boron nitride and MoS2. Their shapes are found to exhibit universal scaling, in agreement with our analysis based on the theory of elasticity of membranes. We also measured the hydrostatic pressure induced by the confinement, which was found to reach tens of MPa inside submicron bubbles. This agrees with our theory estimates and suggests that for even smaller, sub-10 nm bubbles the pressure can be close to 1 GPa and may modify properties of a trapped material. PMID- 27557734 TI - SPG7 and Impaired Emotional Communication. AB - The goal of this report is to describe the genetic mutations of a patient with cerebellar degeneration who had ataxia and impaired emotional communication that led to damage of family relationships. We extracted genomic DNA from peripheral blood lymphocytes and performed whole exome sequencing (WES) in this patient and his unaffected parents and siblings. Found mutations were confirmed by Sanger sequencing in each individual. We found compound heterozygous mutations in the paraplegin (SPG7) gene. One mutated allele has been previously described as a disease-causing missense mutation for spastic paraplegia type 7 (SPG7) (c.1529C > T, p.Ala510Val). The second mutated allele involved a single nucleotide deletion which results in a frameshift in the coding sequence (c.2271delG, p.Met757fs*65). The second allele is similar to, but unique from, other described, SPG7-linked truncation mutations. The abnormal emotional communication in this patient broadens the phenotypic boundary of SPG7. PMID- 27557735 TI - Role of phenazines and cyclic lipopeptides produced by pseudomonas sp. CMR12a in induced systemic resistance on rice and bean. AB - Pseudomonas sp. CMR12a produces two different classes of cyclic lipopeptides (CLPs) (orfamides and sessilins), which all play a role in direct antagonism against soilborne pathogens. Here we show that Pseudomonas sp. CMR12a is also able to induce systemic resistance to Magnaporthe oryzae on rice and to the web blight pathogen Rhizoctonia solani AG2-2 on bean. Plant assays with biosynthesis mutants of Pseudomonas sp. CMR12a impaired in the production of phenazines and/or CLPs and purified metabolites revealed that distinct bacterial determinants are responsible for inducing systemic resistance in these two pathosystems. In rice, mutants impaired in phenazine production completely lost their ability to induce systemic resistance, while a soil drench with pure phenazine-1-carboxamide (PCN) at a concentration of 0.1 or 1 MUM was active in inducing resistance against M. oryzae. In bean, mutants that only produced phenazines, sessilins or orfamides were still able to induce systemic resistance against Rhizoctonia web blight, but a balanced production of these metabolites was needed. This study not only shows that Pseudomonas sp. CMR12a can protect rice to blast disease and bean to web blight disease, but also displays that the determinants involved in induced systemic resistance are plant, pathogen and concentration dependent. PMID- 27557738 TI - The values of grey suits and white coats. PMID- 27557739 TI - The trauma of caring: who's caring for the carers? PMID- 27557737 TI - High-throughput miRNA sequencing and identification of biomarkers for forensically relevant biological fluids. AB - microRNAs (miRNAs) are small noncoding RNAs that regulate cellular processes through modulation of proteins at the translational level. They tend to be highly stable as compared to other RNA species due to their small size and protection by protein and/or lipid matrices. Thus, it is likely that miRNAs, when fully evaluated, will make excellent candidates for body fluid identification. miRNA analysis of body fluids has been the subject of some recent interest in the forensic community. In this study, small RNAs were isolated from individual donations of eight forensically relevant biological fluids (blood, semen, vaginal fluid, menstrual blood, saliva, urine, feces, and perspiration) and subjected to next generation sequencing using the Illumina Hi-Seq platform. Sequencing reads were aligned and annotated against miRbase release 21, resulting in a list of miRNAs and their relative expression levels for each sample analyzed. Body fluids with high bacterial loads (vaginal fluid, saliva, and feces) yielded relatively low annotated miRNA counts, likely due to oversaturation of small RNAs from the endogenous bacteria. Both body fluid specific (miRs-200b, 1246, 320c, 10b-5p, 26b, and 891a) and potential normalization miRNAs (let-7g and i) were identified for further analysis as potential body fluid identification tools for each body fluid. PMID- 27557736 TI - Heterogeneity in oligodendroglia: Is it relevant to mouse models and human disease? AB - There are many lines of evidence indicating that oligodendrocyte progenitor cells and oligodendrocyte populations in the central nervous system (CNS) are heterogeneous based on their developmental origins as well as from morphological and molecular criteria. Whether these distinctions reflect functional heterogeneity is less clear and has been the subject of considerable debate. Recent findings, particularly from knockout mouse models, have provided new evidence for regional variations in myelination phenotypes, particularly between brain and spinal cord. These data raise the possibility that oligodendrocytes in these regions have different functional capacities and/or ability to compensate for loss of a specific gene. The goal of this review is to briefly revisit the evidence for oligodendrocyte heterogeneity and then to present data from transgenic and demyelinating mouse models suggesting functional heterogeneity in myelination, demyelination, and remyelination in the CNS and, finally, to discuss the implications of these findings for human diseases. (c) 2016 Wiley Periodicals, Inc. PMID- 27557740 TI - Health literacy: a key educational role for nurses and a vital tool for improving health. PMID- 27557743 TI - International observership as leadership training. PMID- 27557742 TI - Nursing challenges in China. PMID- 27557744 TI - What does caring mean to nursing and social work students? AB - AIM: The aim of this study in Lithuania was to discover how the meaning of caring is perceived by nursing and social work students. BACKGROUND: Nursing and social work are caring professions, which provide care in different ways. It is still unclear what features constitute the meaning of caring for nursing and social work students as future caring professionals. METHODS: Snowball sampling technique was applied in the study. The data were collected as reflective narratives. Data were analysed using qualitative content analysis. FINDINGS: For nursing and social work students, the meaning of caring comprises mission, proficiency, values and collaboration. These features overlap, but the implementation of caring is dependent on the particular profession. DISCUSSION: Nursing and social work students describe the meaning of caring as holistic assistance to patient/client: the work mission for both. However, the tasks, responsibilities and focus on providing care to a patient/client differ in both professions. LIMITATIONS: Reflective narratives were preferred to semi-structured interviews. The researchers did not contact the participants in person to ask them additional questions. CONCLUSION: The meaning of caring is perceived as a developmental phenomenon, which depends on professional philosophy, practice, continuing learning and experience. Nursing and social work students perceive it as a way of thinking about the individual's being in a profession and acting collaboratively for the wellbeing of others. IMPLICATIONS FOR HEALTH POLICY: Focus on the meaning of caring in nursing and social work (post)graduate education is a premise to shift the training from self- to other-centred, from mono- to multi-disciplinary approach. This is related to the shift of practices towards effective patient-centred team-working within the health system, with the spotlight on caring. PMID- 27557745 TI - International study on nurses' views and experiences of compassion. AB - BACKGROUND: Compassion is considered the cornerstone of nursing practice. However, the recent failures in delivering high-quality compassionate nursing care in the UK's National Health Service have brought the topic of compassion to the attention of the public, service providers, policy makers and academics. AIM: The aim of this study was to explore the nurses' views and experiences of a number of compassion-related issues in nursing and describe similarities and differences at an international level as well as from the different nursing roles of the participating nurses. METHODS: An exploratory, cross-sectional descriptive study, using the International Online Compassion Questionnaire. A total of 1323 nurses from 15 countries completed the questionnaire. RESULTS: The majority of participants (59.5%) defined compassion as "Deep awareness of the suffering of others and wish to alleviate it" but definitions of compassion varied by country. Of participants, 69.6% thought compassion was very important in nursing and more than half (59.6%) of them argued that compassion could be taught. However, only 26.8% reported that the correct amount and level of teaching is provided. The majority of the participants (82.6%) stated that their patients prefer knowledgeable nurses with good interpersonal skills. Only 4.3% noted that they are receiving compassion from their managers. A significant relationship was found between nurses' experiences of compassion and their views about teaching of compassion. CONCLUSION: Our study is unique in identifying the views and experiences of nurses from 15 different countries worldwide. The findings reveal that compassion is neither addressed adequately in nursing education nor supported in the practice environment by managers. LIMITATIONS: Self-report bias was inherent to our survey study design. Furthermore, the individual cultural differences and similarities in the findings are difficult to extrapolate owing to the fact that our analysis was at country level, as well as at the level of the participating nurses. IMPLICATIONS FOR NURSING POLICY: Understanding the influence of culture on nurses' views about compassion is critical in the current multicultural healthcare environment and merits further research. This will potentially drive changes in nursing education (ensuring that compassion is taught to nurses) and in the way healthcare leaders and managers foster a compassionate culture within their organizations (e.g. by leading by example and compassionate to their staff). PMID- 27557746 TI - How do area-level socioeconomic status and gender norms affect partner violence against women? Evidence from Tanzania. AB - OBJECTIVES: To explore how area-level socioeconomic status and gender-related norms influence partner violence against women in Tanzania. METHODS: We analysed data from the 2010 Tanzania Demographic and Health Survey and used multilevel logistic regression to estimate individual and community-level effects on women's risk of current partner violence. RESULTS: Prevalence of current partner violence was 36.1 %; however, variation in prevalence exists across communities. Twenty nine percent of the variation in the logodds of partner violence is due to community-level influences. When adjusting for individual-level characteristics, this variation falls to 10 % and falls further to 8 % when adjusting for additional community-level factors. Higher levels of women's acceptance towards wife beating, male unemployment, and years of schooling among men were associated with higher risk of partner violence; however, higher levels of women in paid work were associated with lower risk. CONCLUSIONS: Area-level poverty and inequitable gender norms were associated with higher risk of partner violence. Empowerment strategies along with addressing social attitudes are likely to achieve reductions in rates of partner violence against women in Tanzania and in other similar low-income country settings. PMID- 27557747 TI - Adrenal fatigue does not exist: a systematic review. AB - BACKGROUND: The term "adrenal fatigue" ("AF") has been used by some doctors, healthcare providers, and the general media to describe an alleged condition caused by chronic exposure to stressful situations. Despite this, "AF" has not been recognized by any Endocrinology society, who claim there is no hard evidence for the existence. The aim of this systematic review is to verify whether there is substantiation for "AF". METHODS: A systematic search was performed at PUBMED, MEDLINE (Ebsco) and Cochrane databases, from the beginning of the data until April 22nd, 2016. Searched key words were: "adrenal" + "fatigue", "adrenal" + "burnout", "adrenal" + "exhaustion", "hypoadrenia", "burnout" + "cortisol", "fatigue" + "cortisol", "clinical" + "burnout", "cortisol" + "vitalility", "adrenal" + "vitality", and "cortisol" + "exhaustion". Eligibility criteria were: (1) articles written in English, (2) cortisol profile and fatigue or energy status as the primary outcome, (3) performed tests for evaluating the adrenal axis, (4) absence of influence of corticosteroid therapy, and (5) absence of confounding diseases. Type of questionnaire to distinct fatigued subjects, population studied, tests performed of selected studies were analyzed. RESULTS: From 3,470 articles found, 58 studies fulfilled the criteria: 33 were carried in healthy individuals, and 25 in symptomatic patients. The most assessed exams were "Direct Awakening Cortisol" (n = 29), "Cortisol Awakening Response" (n = 27) and "Salivary Cortisol Rhythm" (n = 26). DISCUSSION: We found an almost systematic finding of conflicting results derived from most of the studies methods utilized, regardless of the validation and the quality of performed tests. Some limitations of the review include: (1) heterogeneity of the study design; (2) the descriptive nature of most studies; (3) the poor quality assessment of fatigue; (4) the use of an unsubstantiated methodology in terms of cortisol assessment (not endorsed by endocrinologists); (5) false premises leading to an incorrect sequence of research direction; and, (6) inappropriate/invalid conclusions regarding causality and association between different information. CONCLUSION: This systematic review proves that there is no substantiation that "adrenal fatigue" is an actual medical condition. Therefore, adrenal fatigue is still a myth. PMID- 27557748 TI - Acute kidney injury is a powerful independent predictor of mortality in critically ill patients: a multicenter prospective cohort study from Kinshasa, the Democratic Republic of Congo. AB - BACKGROUND: Despite the growing incidence of acute kidney injury (AKI) worldwide, there is little data on the burden and outcomes of AKI in intensive care unit (ICU) in low resource settings. The present study assessed the incidence of AKI and its impact on mortality in ICU in Kinshasa (Democratic Republic of Congo). METHODS: In a prospective cohort study, 476 consecutive critically ill patients (mean age 52 years, 57 % male) were screened for the presence of AKI in seven ICU from January 1st to March 30th, 2015. Serum creatinine was measured by the enzymatic method (Cobas C111 device(r)). AKI and its stages (no AKI, AKI 1, AKI 2 and AKI 3) were defined according to AKIN recommendations. The primary outcome was 28 days mortality. Survival (time-to death) curves were built using the Kaplan Meier methods. Predictors of mortality were assessed by Cox proportional hazards regression models. p < 0.05 defined the level of statistical significance. RESULTS: The cumulative incidence of AKI was 52.7 % with AKI stage 1, 2 and 3 in 23.7 %, 16.2 % and 12.8 % of patients, respectively. Among patients who developed AKI, 146 died (58 %) vs 62 patients (28 %) in the group without AKI. Only 6.5 % of the patients with AKI stage 3 benefited from dialysis. Median survival time was 15.0 days in patients without AKI and 3.0 days, 6.0 days and 8.0 days in patients with AKI stage 3, 2 and 1 (p < 0.001), respectively. In addition to respiratory distress-induced polypnea (HRa 1.60; 95 % CI: 1.08-2.37; p = 0.018), oxygen desaturation (HRa 1.53; 95 % CI: 1.13-2.08; p = 0.006) and multi-organic involvement (HRa 1.63; 95 % CI: 1.15-2.30), AKI emerged as an independent predictor of death (HRa 1.82; 95 % CI: 1.34-2.48; p < 0.001). CONCLUSION: More than half of critically ill patients in the present cohort developed AKI which contributed substantially to short-term mortality, highlighting the need for its prevention, early detection and management as well as the availability of dialysis in ICU. PMID- 27557749 TI - Integrative effect of drought and low temperature on litchi (Litchi chinensis Sonn.) floral initiation revealed by dynamic genome-wide transcriptome analysis. AB - Floral induction in litchi is influenced by multiple environment cues including temperature and soil water condition. In the present study, we determined that a combined treatment consisting of 14-day drought imposed prior to exposure to 35 day low temperature (T3) significantly promoted litchi flowering relative to the low temperature alone (T2), suggesting an integrative effect of drought and low temperature on litchi floral initiation. Analysis of transcriptomic changes in leaves from different treatments showed that 2,198 and 4,407 unigenes were differentially expressed in response to drought and low temperature, respectively. 1,227 of these unigenes were expressed in response to both treatments, implying an interaction of drought and low temperature on expression of genes involved in litchi floral initiation. Additionally, 932 unigenes were consistently differentially expressed during floral induction between T2 and T3 plants, which potentially accounts for the difference of flowering time. Thirty eight transcription factors out of these 932 unigenes were identified as hub genes with central roles in regulation of litchi floral induction. The expression of litchi homologs of well-known flowering genes was also investigated, and one Flowering Locus T (FT) homolog may play a crucial role in litchi flowering in responses to drought and low temperature. PMID- 27557750 TI - High quality standards for a large-scale prospective population-based observational cohort: Constances. AB - BACKGROUND: Long-term multicentre studies are subject to numerous factors that may affect the integrity of their conclusions. Quality control and standardization of data collection are crucial to minimise the biases induced by these factors. Nevertheless, tools implemented to manage biases are rarely described in publications about population-based cohorts. This report aims to describe the processes implemented to control biases in the Constances cohort taking lung function results as an example. METHODS: Constances is a general purpose population-based cohort of 200,000 participants. Volunteers attend physical examinations at baseline and then every 5 years at selected study sites. Medical device specifications and measurement methods have to comply with Standard Operating Procedures developed by experts. Protocol deviations are assessed by on-site inspections and database controls. In February 2016, more than 94,000 participants yielding around 30 million readings from physical exams, had been covered by our quality program. RESULTS: Participating centres accepted to revise their practices in accordance with the study research specifications. Distributors of medical devices were asked to comply with international guidelines and Constances requirements. Close monitoring enhanced the quality of measurements and recordings of the physical exams. Regarding lung function testing, spirometry acceptability rates per operator doubled in some sites within a few months and global repeatability reached 96.7 % for 29,772 acceptable maneuvers. CONCLUSIONS: Despite Constances volunteers being followed in multiple sites with heterogeneous materials, the investment of significant resources to set up and maintain a continuous quality management process has proved effective in preventing drifts and improving accuracy of collected data. PMID- 27557752 TI - Increased serum GDF11 concentration is associated with a high prevalence of osteoporosis in elderly native Chinese women. AB - Osteoporosis is an age-related disease. Many studies have confirmed the anti aging effect of growth differentiation factor 11 (GDF11), but the action of GDF11 on bone metabolism remains unclear. In this study, we aimed to investigate the relationship between serum GDF11 levels and the prevalence of osteoporosis. Our data indicate negative correlations between serum GDF11 levels and BMD at the lumbar spine and femoral neck. The serum GDF11 levels were grouped into quartile intervals, and the prevalence and risk of osteoporosis were found be markedly greater with increased GDF11 levels. This study demonstrated that GDF11 was negatively correlated with BMD in elderly Chinese women. Furthermore, osteoporotic risk was significantly increased with increases in GDF11 levels. PMID- 27557751 TI - RNA sequencing from neural ensembles activated during fear conditioning in the mouse temporal association cortex. AB - The stable formation of remote fear memories is thought to require neuronal gene induction in cortical ensembles that are activated during learning. However, the set of genes expressed specifically in these activated ensembles is not known; knowledge of such transcriptional profiles may offer insights into the molecular program underlying stable memory formation. Here we use RNA-Seq to identify genes whose expression is enriched in activated cortical ensembles labeled during associative fear learning. We first establish that mouse temporal association cortex (TeA) is required for remote recall of auditory fear memories. We then perform RNA-Seq in TeA neurons that are labeled by the activity reporter Arc dVenus during learning. We identify 944 genes with enriched expression in Arc dVenus+ neurons. These genes include markers of L2/3, L5b, and L6 excitatory neurons but not glial or inhibitory markers, confirming Arc-dVenus to be an excitatory neuron-specific but non-layer-specific activity reporter. Cross comparisons to other transcriptional profiles show that 125 of the enriched genes are also activity-regulated in vitro or induced by visual stimulus in the visual cortex, suggesting that they may be induced generally in the cortex in an experience-dependent fashion. Prominent among the enriched genes are those encoding potassium channels that down-regulate neuronal activity, suggesting the possibility that part of the molecular program induced by fear conditioning may initiate homeostatic plasticity. PMID- 27557753 TI - Erythrocyte oxidative stress is associated with cell deformability in patients with retinal vein occlusion. AB - : Essentials Retinal vein occlusion (RVO), characterized by blood hyperviscosity, has an unclear pathogenesis. We aimed to find out if hemorheological profile is altered by oxidative stress in RVO patients. Red blood cell (RBC) oxidative stress is associated to whole blood viscosity and RBC deformability. Reactive oxygen species alter RBC membrane rigidity, playing a key role in RVO pathogenesis. SUMMARY: Background Retinal vein occlusion (RVO) is characterized by vision loss resulting from hypoperfusion and hypoxia of the retina. RVO pathogenesis is not yet fully understood, although blood hyperviscosity has been observed. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to microvascular perfusion and oxygen delivery. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Objectives To determine whether erythrocytes from RVO patients show signs of oxidative stress, and whether this condition can modify the hemorheologic profile in these patients. Patients and Methods We analyzed the entire hemorheologic profile and erythrocyte oxidative stress - reactive oxygen species (ROS) production and membrane lipid peroxidation - in 128 RVO patients and 128 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results In RVO patients, erythrocyte oxidative stress was present and positively correlated with whole blood viscosity and erythrocyte deformability. Multivariate linear regression analysis after adjustment for age, cardiovascular risk factors, medications, leukocyte number and mean corpuscular volume indicated that erythrocyte-derived ROS and erythrocyte lipid peroxidation were significantly and positively correlated with erythrocyte membrane viscosity and deformability. Moreover, in vitro experiments demonstrated that ROS have a key role in erythrocyte membrane fluidity. Conclusions Our findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of RVO, and pave the way to new therapeutic interventions. PMID- 27557755 TI - Stereoretentive Copper-Catalyzed Directed Thioglycosylation of C(sp2 )-H Bonds of Benzamides. AB - An efficient thioglycosylation of C(sp2 )-H bonds with thiosugars has been established for the first time. Using only Cu(OAc)2 ?H2 O as a catalyst and Ag2 CO3 as an additive in DMSO, the protocol proved to have broad scope, and a variety of complex thioglycosides have been prepared in good yields with exclusive beta-selectivity. PMID- 27557754 TI - Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin. AB - OBJECTIVE: To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). METHODS: A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms. Based on ET registry data, TEs in anagrelide treated patients (n = 139) were compared with HU + ASA-treated patients (n = 141). RESULTS: Patients were followed up for (median) 6 yr. TEs were reported in significantly fewer anagrelide-treated patients versus HU + ASA (15.1% versus 49.6%; P < 0.001). Numbers of major arterial and major venous events were similar between the groups, although there were over fivefold more minor arterial and minor venous events in the HU + ASA group (P < 0.001). While median age at diagnosis was older and length of follow-up shorter in the HU + ASA group (P < 0.05), this did not influence TE incidence; medication and TE before diagnosis only influenced TE incidence. CONCLUSIONS: Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous TEs versus HU + ASA over 6 yr. Risk of TE after diagnosis was significantly increased if the patient had TE before diagnosis. PMID- 27557756 TI - Levofloxacin-induced rhabdomyolysis: a case report. AB - BACKGROUND: Rhabdomyolysis secondary to quinolones is not frequent. There are scarce reports in the literature associating rhabdomyolysis to levofloxacin. We describe a case of levofloxacin-induced rhabdomyolysis. CASE PRESENTATION: A 52 year-old African-American man presented with muscle tightness after taking three doses of levofloxacin. He had elevated creatine kinase without acute kidney injury. His symptoms resolved after discontinuation of levofloxacin and supportive care. CONCLUSIONS: It is fascinating that our patient has a prior history of rhabdomyolysis, likely from levofloxacin. Our case highlights the need to be mindful of this potentially life-threatening complication of levofloxacin. PMID- 27557757 TI - What Have We Learned About Synthetic Promoter Construction? AB - The molecular components of transcriptional regulation are modular. Transcription factors have domains for specific functions such as DNA binding, dimerization, and protein-protein interactions associated with transcriptional activation and repression. Similarly, promoters are modular. They consist of combinations of cis acting elements that are the binding sites for transcription factors. It is this promoter architecture that largely determines the expression pattern of a gene. The modular nature of promoters is supported by the observation that many cis acting elements retain their activities when they are taken out of their native promoter context and used as building blocks in synthetic promoters. We therefore have a large collection of cis-acting elements to use in building synthetic promoters and many minimal promoters upon which to build them. This review discusses what we have learned concerning how to use these building blocks to make synthetic promoters. It has become clear that we can increase the strength of a promoter by adding increasing numbers of cis-acting elements. However, it appears that there may be a sweet spot with regard to inducibility as promoters with increasing numbers of copies of an element often show increased background expression. Spacing between elements appears important because if elements are placed too close together activity is lost, presumably due to reduced transcription factor binding due to steric hindrance. In many cases, promoters that contain combinations of cis-acting elements show better expression characteristics than promoters that contain a single type of element. This may be because multiple transcription factor binding sites in the promoter places it at the end of multiple signal transduction pathways. Finally, some cis-acting elements form functional units with other elements and are inactive on their own. In such cases, the complete unit is required for function in a synthetic promoter. Taken together, we have learned much about how to construct synthetic promoters and this knowledge will be crucial in both designing promoters to drive transgenes and also as components of defined regulatory networks in synthetic biology. PMID- 27557759 TI - The Identification of Cis-Regulatory Sequence Motifs in Gene Promoters Based on SNP Information. AB - Conservation of particular molecular sequence motifs throughout evolution is a strong indicator of their functional relevance as selective pressure likely prevented the accumulation of mutations. Known as "phylogenetic footprinting", this rationale has been exploited for the identification of novel functional motifs using sequence information from sequence alignments of diverse species, in particular transcription factor binding site motifs in aligned gene promoter sequences of orthologous genes. With the rapid advances of sequencing technologies, whole genome sequence information is accumulating not only across different species, but increasingly for variants of the same species exhibiting relatively little sequence variability, primarily present as single nucleotide polymorphisms (SNPs). Here, we lay out the basic strategy for the identification of functional cis-regulatory motifs in gene promoter regions based on SNP information. PMID- 27557758 TI - Quantitative Analysis of Cis-Regulatory Element Activity Using Synthetic Promoters in Transgenic Plants. AB - Synthetic promoters, introduced stably or transiently into plants, are an invaluable tool for the identification of functional regulatory elements and the corresponding transcription factor(s) that regulate the amplitude, spatial distribution, and temporal patterns of gene expression. Here, we present a protocol describing the steps required to identify and characterize putative cis regulatory elements. These steps include application of computational tools to identify putative elements, construction of a synthetic promoter upstream of luciferase, identification of transcription factors that regulate the element, testing the functionality of the element introduced transiently and/or stably into the species of interest followed by high-throughput luciferase screening assays, and subsequent data processing and statistical analysis. PMID- 27557760 TI - Quantitative Analysis of Protein-DNA Interaction by qDPI-ELISA. AB - The specific binding of DNA-binding proteins to their cognate DNA motifs is a crucial step for gene expression control and chromatin organization in vivo. The development of methods for the identification of in vivo binding regions by, e.g. chromatin immunoprecipitation (ChIP) or DNA adenine methyltransferase identification (Dam-ID) added an additional level of qualitative information for data mining in systems biology or applications in synthetic biology. In this respect, the in vivo techniques outpaced methods for thorough characterization of protein-DNA interaction and, especially, of the binding motifs at single base pair resolution. The elucidation of DNA-binding capacities of proteins is frequently done with methods such as yeast one-hybrid, electrophoretic mobility shift assay (EMSA) or systematic evolution of ligands by exponential enrichment (SELEX) that provide only qualitative binding information and are not suited for automation or high-throughput screening of several DNA motifs. Here, we describe the quantitative DNA-protein-Interaction-ELISA (qDPI-ELISA) protocol, which makes use of fluorescent fusion proteins and, hence, is faster and easier to handle than the classical DPI-ELISA. Although every DPI-ELISA experiment delivers quantitative information, the qDPI-ELISA has an increased consistency, as it does not depend on immunological detection. We demonstrate the high comparability between probes and different protein extracts in qDPI-ELISA experiments. PMID- 27557761 TI - Analyzing Synthetic Promoters Using Arabidopsis Protoplasts. AB - This chapter describes a transient protoplast co-transfection method that can be used to quantitatively study in vivo the activity and function of promoters and promoter elements (reporters), and their induction or repression by transcription factors (effectors), stresses, hormones, or metabolites. A detailed protocol for carrying out transient co-transfection assays with Arabidopsis At7 protoplasts and calculating the promoter activity is provided. PMID- 27557762 TI - Selecting Hypomethylated Genomic Regions Using MRE-Seq. AB - Here, we describe a method capable of filtering the hypomethylated part of plant genomes, the so-called hypomethylome. The principle of the method is based on the filtration and sequence analysis of small DNA fragments generated by methylation sensitive four-cutter restriction endonucleases, possessing ((5me))CpG motifs in their recognition sites. The majority of these fragments represent genes and their flanking regions containing also regulatory elements-the gene space of the genome. Besides the enrichment of the gene space, another advantage of the method is the simultaneous depletion of repetitive elements due to their methylated nature and its easy application on complex and large plant genomes. Additionally to the wet lab procedure, we describe how to analyze the data using bioinformatics methods and how to apply the method to comparative studies. PMID- 27557763 TI - Spatio-Temporal Imaging of Promoter Activity in Intact Plant Tissues. AB - Localization and quantification of expression levels of genes help to determine their function. Localization of gene expression is often achieved through the study of their promoter activity. Three main reporter genes beta-glucuronidase (GUS), green fluorescent protein (GFP), and luciferase (LUC) have been intensively used to characterize promoter activities, each having its own specificities and advantages. Among them, the LUC reporter gene is best suitable for the analysis of the promoter activity of genes in intact living plants. Here, we describe a LUC-based method that allows to precisely localize and quantify promoter activity at the whole plant level, and to study the mechanisms that are involved in long-distance regulation of gene expression in Arabidopsis thaliana. Imaging LUC signals with a low-light CCD camera allows monitoring promoter activity in time and space in the transgenic plant harboring the promoter fused with the LUC gene. In addition, it allows quantifying change of promoter activities in plant during several hours. PMID- 27557764 TI - Novel Synthetic Promoters from the Cestrum Yellow Leaf Curling Virus. AB - Constitutive promoters direct gene expression uniformly in most tissues and cells at all stages of plant growth and development; they confer steady levels of transgene expression in plant cells and hence their demand is high in plant biology. The gene silencing due to promoter homology can be avoided by either using diverse promoters isolated from different plant and viral genomes or by designing synthetic promoters. The aim of this chapter was to describe the basic protocols needed to develop and analyze novel, synthetic, nearly constitutive promoters from Cestrum yellow leaf curling virus (CmYLCV) through promoter/leader deletion and activating cis-sequence analysis. We also describe the methods to evaluate the strength of the promoters efficiently in various transient expression systems like agroinfiltration assay, gene-gun method, and assay in tobacco protoplasts. Besides, the detailed methods for developing transgenic plants (tobacco and Arabidopsis) for evaluation of the promoter using the GUS reporter gene are also described. The detailed procedure for electrophoretic mobility shift assay (EMSA) coupled with super-shift EMSA analysis are also described for showing the binding of tobacco transcription factor, TGA1a to cis elements in the CmYLCV distal promoter region. PMID- 27557765 TI - Fast and Efficient Cloning of Cis-Regulatory Sequences for High-Throughput Yeast One-Hybrid Analyses of Transcription Factors. AB - Yeast one-hybrid (Y1H) assay has been proven to be a powerful technique to characterize in vivo the interaction between a given transcription factor (TF), or its DNA-binding domain (DBD), and target DNA sequences. Comprehensive characterization of TF/DBD and DNA interactions should allow designing synthetic promoters that would undoubtedly be valuable for biotechnological approaches. Here, we use the ligation-independent cloning system (LIC) in order to enhance the cloning efficiency of DNA motifs into the pHISi Y1H vector. LIC overcomes important limitations of traditional cloning technologies, since any DNA fragment can be cloned into LIC compatible vectors without using restriction endonucleases, ligation, or in vitro recombination. PMID- 27557766 TI - The Physcomitrella patens System for Transient Gene Expression Assays. AB - Transient expression assays are valuable techniques to study in vivo the transcriptional regulation of gene expression. These methods allow to assess the transcriptional properties of a given transcription factor (TF) or a complex of regulatory proteins against specific DNA motifs, called cis-regulatory elements. Here, we describe a fast, efficient, and reliable method based on the use of Physcomitrella patens protoplasts that allows the study of gene expression in a qualitative and quantitative manner by combining the advantage of GFP (green fluorescent protein) as a marker of promoter activity with flow cytometry for accurate measurement of fluorescence in individual cells. PMID- 27557767 TI - Analysis of Microbe-Associated Molecular Pattern-Responsive Synthetic Promoters with the Parsley Protoplast System. AB - Plants recognize pathogens by microbe-associated molecular patterns (MAMPs) and subsequently induce an immune response. The regulation of gene expression during the immune response depends largely on cis-sequences conserved in promoters of MAMP-responsive genes. These cis-sequences can be analyzed by constructing synthetic promoters linked to a reporter gene and by testing these constructs in transient expression systems. Here, the use of the parsley (Petroselinum crispum) protoplast system for analyzing MAMP-responsive synthetic promoters is described. The synthetic promoter consists of four copies of a potential MAMP-responsive cis sequence cloned upstream of a minimal promoter and the uidA reporter gene. The reporter plasmid contains a second reporter gene, which is constitutively expressed and hence eliminates the requirement of a second plasmid used as a transformation control. The reporter plasmid is transformed into parsley protoplasts that are elicited by the MAMP Pep25. The MAMP responsiveness is validated by comparing the reporter gene activity from MAMP-treated and untreated cells and by normalizing reporter gene activity using the constitutively expressed reporter gene. PMID- 27557768 TI - A Framework for Discovering, Designing, and Testing MicroProteins to Regulate Synthetic Transcriptional Modules. AB - Transcription factors often form protein complexes and give rise to intricate transcriptional networks. The regulation of transcription factor multimerization plays a key role in the fine-tuning of the underlying transcriptional pathways and can be exploited to modulate synthetic transcriptional modules. A novel regulation of protein complex formation is emerging: microProteins-truncated transcription factors-engage in protein-protein interactions with transcriptional complexes and modulate their transcriptional activity. Here, we outline a strategy for the discovery, design, and test of putative miPs to fine-tune the activity of transcription factors regulating synthetic or natural transcriptional circuits. PMID- 27557769 TI - Simultaneous Analysis of Multiple Promoters: An Application of the PC-GW Binary Vector Series. AB - With the advances in the field of synthetic biology, there is an increasing demand for multi-gene cloning technologies. Molecular cloning to generate multi gene constructs can be performed by restriction digestion, or by recombination based cloning strategies such as Gateway((r)). This chapter details cloning, transformation, and selection procedures involved in generation of multi-gene expressing transgenic plants. Methods are described for cloning five distinct promoter-reporter fusion constructs into the PC-GW-BAR vector (from the PC-GW vector series) using Gateway((r)) technology and meganuclease sites. Further, transformation and selection methods are described for the biofuel crop Camelina sativa from the Brassicaceae family. These methods would be constructive toward generating multi-gene expressing plants for simultaneous expression analysis of five promoters in a short time period. PMID- 27557770 TI - GenoCAD Plant Grammar to Design Plant Expression Vectors for Promoter Analysis. AB - With the rapid advances in prediction tools for discovery of new promoters and their cis-elements, there is a need to improve plant expression methodologies in order to facilitate a high-throughput functional validation of these promoters in planta. The promoter-reporter analysis is an indispensible approach for characterization of plant promoters. It requires the design of complex plant expression vectors, which can be challenging. Here, we describe the use of a plant grammar implemented in GenoCAD that will allow the users to quickly design constructs for promoter analysis experiments but also for other in planta functional studies. The GenoCAD plant grammar includes a library of plant biological parts organized in structural categories to facilitate their use and management and a set of rules that guides the process of assembling these biological parts into large constructs. PMID- 27557771 TI - Bioinformatic Identification of Conserved Cis-Sequences in Coregulated Genes. AB - Bioinformatics tools can be employed to identify conserved cis-sequences in sets of coregulated plant genes because more and more gene expression and genomic sequence data become available. Knowledge on the specific cis-sequences, their enrichment and arrangement within promoters, facilitates the design of functional synthetic plant promoters that are responsive to specific stresses. The present chapter illustrates an example for the bioinformatic identification of conserved Arabidopsis thaliana cis-sequences enriched in drought stress-responsive genes. This workflow can be applied for the identification of cis-sequences in any sets of coregulated genes. The workflow includes detailed protocols to determine sets of coregulated genes, to extract the corresponding promoter sequences, and how to install and run a software package to identify overrepresented motifs. Further bioinformatic analyses that can be performed with the results are discussed. PMID- 27557772 TI - In Silico Expression Analysis. AB - Information on the specificity of cis-sequences enables the design of functional synthetic plant promoters that are responsive to specific stresses. Potential cis sequences may be experimentally tested, however, correlation of genomic sequence with gene expression data enables an in silico expression analysis approach to bioinformatically assess the stress specificity of candidate cis-sequences prior to experimental verification. The present chapter demonstrates an example for the in silico validation of a potential cis-regulatory sequence responsive to cold stress. The described online tool can be applied for the bioinformatic assessment of cis-sequences responsive to most abiotic and biotic stresses of plants. Furthermore, a method is presented based on a reverted in silico expression analysis approach that predicts highly specific potentially functional cis regulatory elements for a given stress. PMID- 27557773 TI - FootprintDB: Analysis of Plant Cis-Regulatory Elements, Transcription Factors, and Binding Interfaces. AB - FootprintDB is a database and search engine that compiles regulatory sequences from open access libraries of curated DNA cis-elements and motifs, and their associated transcription factors (TFs). It systematically annotates the binding interfaces of the TFs by exploiting protein-DNA complexes deposited in the Protein Data Bank. Each entry in footprintDB is thus a DNA motif linked to the protein sequence of the TF(s) known to recognize it, and in most cases, the set of predicted interface residues involved in specific recognition. This chapter explains step-by-step how to search for DNA motifs and protein sequences in footprintDB and how to focus the search to a particular organism. Two real-world examples are shown where this software was used to analyze transcriptional regulation in plants. Results are described with the aim of guiding users on their interpretation, and special attention is given to the choices users might face when performing similar analyses. PMID- 27557774 TI - RSAT::Plants: Motif Discovery Within Clusters of Upstream Sequences in Plant Genomes. AB - The plant-dedicated mirror of the Regulatory Sequence Analysis Tools (RSAT, http://plants.rsat.eu ) offers specialized options for researchers dealing with plant transcriptional regulation. The website contains whole-sequenced genomes from species regularly updated from Ensembl Plants and other sources (currently 40), and supports an array of tasks frequently required for the analysis of regulatory sequences, such as retrieving upstream sequences, motif discovery, motif comparison, and pattern matching. RSAT::Plants also integrates the footprintDB collection of DNA motifs. This protocol explains step-by-step how to discover DNA motifs in regulatory regions of clusters of co-expressed genes in plants. It also explains how to empirically control the significance of the result, and how to associate the discovered motifs with putative binding factors. PMID- 27557775 TI - RSAT::Plants: Motif Discovery in ChIP-Seq Peaks of Plant Genomes. AB - In this protocol, we explain how to run ab initio motif discovery in order to gather putative transcription factor binding motifs (TFBMs) from sets of genomic regions returned by ChIP-seq experiments. The protocol starts from a set of peak coordinates (genomic regions) which can be either downloaded from ChIP-seq databases, or produced by a peak-calling software tool. We provide a concise description of the successive steps to discover motifs, cluster the motifs returned by different motif discovery algorithms, and compare them with reference motif databases. The protocol is documented with detailed notes explaining the rationale underlying the choice of options. The interpretation of the results is illustrated with an example from the model plant Arabidopsis thaliana. PMID- 27557776 TI - [Gold as an alternative in the treatment of RA patients with malignancies]. PMID- 27557778 TI - Corrigendum: Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis. PMID- 27557777 TI - Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining "symptomatic" versus "asymptomatic" HAND. AB - The criteria for differentiating symptomatic from asymptomatic HIV-associated neurocognitive disorder require evaluation of (1) cognitive impairment, (2) daily functioning declines, and (3) whether the functional declines are attributable to cognitive versus physical problems. Many providers rely only on self-report to evaluate these latter criteria. However, the accuracy of patient-provided information may be limited. This study evaluated the validity of self-assessment for HIV-associated neurocognitive disorder (HAND) diagnoses by comparing objective findings with self-report of criteria 2 and 3 above. Self-reports were used to stratify 277 cognitively impaired HIV+ individuals into functionally dependent (n = 159) and independent (n = 118) groups, followed by group comparisons of objective functional problems. The dependent group was then divided into those who self-attributed their functional dependence to only cognitive (n = 80) versus only physical (n = 79) causes, for further comparisons on objective findings. The functionally dependent group was significantly worse than the independent group on all objective disability characteristics except severity of cognitive impairment, while those who attributed their dependence to physical (versus cognitive) factors were similar on all objective physical, cognitive, and functioning variables. Of note, 28 % of physical attributors showed no physical abnormalities on neuromedical examinations. Results suggest that patient report is consistently associated with objective measures of functional loss; in contrast, patient identification of physical versus cognitive causes is poorly associated with objective criteria. These findings caution against relying solely on patient self-report to determine whether functional disability in cognitively impaired HIV+ individuals can be attributed to strictly physical causes. PMID- 27557779 TI - Effects of Nitrogen and Shading on Root Morphologies, Nutrient Accumulation, and Photosynthetic Parameters in Different Rice Genotypes. AB - Nitrogen availability and illumination intensity are two key factors which affect rice growth. However, their influences on total nitrogen accumulation, photosynthetic rate, root morphologies, and yields are not fully understood. We conducted two field experiments to (1) evaluate the effects of shading under different N treatments on photosynthetic parameters, root morphologies, total nutrient accumulation, and grain yields of rice; and (2) elucidate the relationship between total nutrient accumulation and root morphologies under different shading conditions and nitrogen treatments. Three nitrogen rates, three shading treatments, and three different rice cultivars were used in two field experiments. Double shading during the grain-filling stage decreased total nutrient accumulation, altered root morphological characteristics, and decreased yields in rice. There were also significant interaction effects between nitrogen and shading on photosynthetic rate, transpiration rate, and total root length, root superficial area, and root volume. Significant interactions were found among cultivars and shading for photosynthetic rate and transpiration rate. Correlation analysis revealed that total nitrogen accumulation (TNA) and potassium accumulation (TKA) were significantly positively correlated with total root length, root superficial area, and root volume. N application could alleviate the detrimental effects of shading on total nutrient accumulation and grain yield in rice. PMID- 27557780 TI - From 0 to II in One-Electron Steps: A Series of Ruthenium Complexes Supported by TropPPh2. AB - We report the synthesis of a series of ruthenium complexes supported by the phosphine olefin ligand tropPPh2 (trop=5-H-dibenzo-[a,d]cyclohepten-5-yl) in the oxidation states 0, +I, and +II, formed via successive one-electron oxidization steps from Ru(0) (tropPPh2 )2 . The bidentate character of the tropPPh2 ligand and its steric hindrance force the complexes to adopt uncommon geometries, which were investigated by X-ray diffraction analysis. EPR data of the mononuclear Ru(I) complex reveal couplings of the unpaired spin with the ruthenium and two phosphorus nuclei, as well as the olefinic protons which show that the spin is mainly localized on the Ru(I) center. PMID- 27557781 TI - Synergistic and compensatory effects of two point mutations conferring target site resistance to fipronil in the insect GABA receptor RDL. AB - Insecticide resistance can arise from a variety of mechanisms, including changes to the target site, but is often associated with substantial fitness costs to insects. Here we describe two resistance-associated target-site mutations that have synergistic and compensatory effects that combine to produce high and persistent levels of resistance to fipronil, an insecticide targeting on gamma aminobytyric acid (GABA) receptors. In Nilaparvata lugens, a major pest of rice crops in many parts of Asia, we have identified a single point mutation (A302S) in the GABA receptor RDL that has been identified previously in other species and which confers low levels of resistance to fipronil (23-fold) in N. lugans. In addition, we have identified a second resistance-associated RDL mutation (R300Q) that, in combination with A302S, is associated with much higher levels of resistance (237-fold). The R300Q mutation has not been detected in the absence of A302S in either laboratory-selected or field populations, presumably due to the high fitness cost associated with this mutation. Significantly, it appears that the A302S mutation is able to compensate for deleterious effects of R300Q mutation on fitness cost. These findings identify a novel resistance mechanism and may have important implications for the spread of insecticide resistance. PMID- 27557782 TI - Long-term storage does not impact the quality of cryopreserved human ovarian tissue. AB - BACKGROUND: Ovarian tissue cryopreservation is an emerging technique, also addressed to very young cancer patients, for whom it is not possible to perform an ovarian stimulation for oocytes freezing, before gonadotoxic treatment. In this cases, ovarian tissue must be cryopreserved for a long period of time and it is very important to know if it maintains fertility function after a long period of storage. Here we aimed to assess the effect of long-term storage on preservation and viability of cryopreserved human ovarian tissue. METHODS: Descriptive study of three cases of cancer patients whose cryopreserved ovarian tissue remained stored for 18 years. Long-term stored tissue was examined by histological and immunohistochemical analysis, transmission electron microscopy, TUNEL assay and LIVE/DEAD viability/citotoxicity test. RESULTS: Ovarian tissue stored for 18 years showed a good morphology. Follicles presented negative staining for estrogen and progesterone receptors, positive staining for ki67 in granulosa cells and/or oocytes and for bcl2 in granulosa cells. Regarding stroma, patch/focal positive expression was found for estrogen receptor and ki67, diffusely positive expression for progesterone receptor and bcl2. After long-term storage, ultrastructural examination showed sub-cellular integrity of follicles and interstitial oedema foci. No apoptosis was observable by TUNEL assay. Stromal cell viability remained >97 % during the culture period. CONCLUSION: The evaluation of different aspects of the tissue provides evidence that the storage time does not impact on tissue quality and gives hope especially to cancer girls, whose tissues could remain cryopreserved for a very long time. PMID- 27557784 TI - Health at the Sub-catchment Scale: Typhoid and Its Environmental Determinants in Central Division, Fiji. AB - The impact of environmental change on transmission patterns of waterborne enteric diseases is a major public health concern. This study concerns the burden and spatial nature of enteric fever, attributable to Salmonella Typhi infection in the Central Division, Republic of Fiji at a sub-catchment scale over 30-months (2013-2015). Quantitative spatial analysis suggested relationships between environmental conditions of sub-catchments and incidence and recurrence of typhoid fever. Average incidence per inhabited sub-catchment for the Central Division was high at 205.9/100,000, with cases recurring in each calendar year in 26% of sub-catchments. Although the numbers of cases were highest within dense, urban coastal sub-catchments, the incidence was highest in low-density mountainous rural areas. Significant environmental determinants at this scale suggest increased risk of exposure where sediment yields increase following runoff. The study suggests that populations living on large systems that broaden into meandering mid-reaches and floodplains with alluvial deposition are at a greater risk compared to small populations living near small, erosional, high energy headwaters and small streams unconnected to large hydrological networks. This study suggests that anthropogenic alteration of land cover and hydrology (particularly via fragmentation of riparian forest and connectivity between road and river networks) facilitates increased transmission of typhoid fever and that environmental transmission of typhoid fever is important in Fiji. PMID- 27557783 TI - Clinical, pharmacodynamic and pharmacokinetic results of a prospective phase II study on oral metronomic vinorelbine and dexamethasone in castration-resistant prostate cancer patients. AB - The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharmacokinetic profiles, of oral metronomic vinorelbine (VNR) plus dexamethasone (DEX) in metastatic castration-resistant prostate cancer (mCRPC) patients. Fourty-one patients (92 % chemotherapy-resistant) received 30 mg/day VNR p.o. thrice a week plus 1 mg/day DEX p.o. until disease progression. Plasma soluble B cell antigen 7 homolog 3 (sB7-H3), vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1), were measured by ELISA. Plasma VNR was detected using a LC-MS-MS system. The fraction of patients free of progression, defined by criteria of the Prostate Cancer Clinical Trials Working Group 2, at 3 months was 61 %. PSA decrease >=50 % from baseline was observed in 35 % of patients. Median PFS and OS were 4 months (95 % CI, 2.8-6.9) and 17.5 months (95 % CI, 10.8-24.5), respectively. Toxicity was mild, and no grade 4 toxicities were found. The mean plasma VNR Cmax ranged from 1 to 2.7 ng/ml (Tmax 1.1 h) and no evidence of drug accumulation was found. A moderate relationship was found between plasma sB7-H3 and PSA values (r = 0.565; P = 0.0094) at the baseline. Increased PFS (11.3 vs. 2.8 months; P = 0.0298) was observed in patients with sB7-H3 levels <30.25 ng/mL. Plasma VEGF AUC0-24day increased in non responders (P < 0.0001), whereas responders maintained higher plasma TSP-1 AUC0 24day (P = 0.0063). In conclusion, metronomic VNR plus DEX showed favourable activity, and a low toxicity profile, in mCRPC patients. Plasma sB7-H3, VEGF and TSP-1 levels are potential pharmacodynamic markers at the reached low plasma concentrations of vinorelbine metronomically administered. PMID- 27557785 TI - Associations between the patient-centered medical home and preventive care and healthcare quality for non-elderly adults with mental illness: A surveillance study analysis. AB - BACKGROUND: Patient-centered medical homes (PCMHs) may improve outcomes for non elderly adults with mental illness, but the extent to which PCMHs are associated with preventive care and healthcare quality for this population is largely unknown. Our study addresses this gap by assessing the associations between receipt of care consistent with the PCMH and preventive care and healthcare quality for non-elderly adults with mental illness. METHODS: This surveillance study used self-reported data for 6,908 non-elderly adults with mental illness participating in the 2007-2012 Medical Expenditure Panel Survey. Preventive care and healthcare quality measures included: participant rating of all healthcare; cervical, breast, and colorectal cancer screening; current smoking; smoking cessation advice; flu shot; foot exam and eye exam for people with diabetes; and follow-up after emergency room visit for mental illness. Multiple logistic regression models were developed to compare the odds of meeting preventive care and healthcare quality measures for participants without a usual source of care, participants with a non-PCMH usual source of care, and participants who received care consistent with the PCMH. RESULTS: Compared to participants without a usual source of care, those with a non-PCMH usual source of care had better odds of meeting almost all measures examined, while those who received care consistent with the PCMH had better odds of meeting most measures. Participants who received care consistent with the PCMH had better odds of meeting only one measure compared to participants with a non-PCMH usual source of care. CONCLUSIONS: Compared with having a non-PCMH usual source of care, receipt of care consistent with the PCMH does not appear to be associated with most preventive care or healthcare quality measures. These findings raise concerns about the potential value of the PCMH for non-elderly adults with mental illness and suggest that alternative models of primary care are needed to improve outcomes and address disparities for this population. PMID- 27557786 TI - Evaluation of Immunogenicity of Nivolumab Monotherapy and Its Clinical Relevance in Patients With Metastatic Solid Tumors. AB - Nivolumab is a fully human IgG4 monoclonal antibody targeting the programmed death-1 (PD-1) receptor that blocks interactions between PD-1 and its ligands on tumor cells to prevent T-cell exhaustion in patients with cancer. It has demonstrated efficacy in multiple tumor types, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. This analysis assessed the immunogenicity of nivolumab and its impact on pharmacokinetics, safety, and efficacy in patients with solid tumors enrolled in 6 clinical studies. The incidence and prevalence of antidrug antibodies (ADAs) were determined by validated electrochemiluminescence assays in samples collected during nivolumab treatment and up to 100 days after the last dose. Confirmed positive samples from the 6 studies were also tested for presence of neutralizing antibodies (NAbs). Among 1086 nivolumab-treated patients, 138 patients (12.7%) were ADA positive (relative to baseline), only 3 (0.3%) of whom were persistently positive for ADA, and 9 (0.8%) were NAb positive at 1 time point. The presence of ADAs was not associated with hypersensitivity, infusion reactions, or loss of efficacy and had minimal impact on nivolumab clearance. Additionally, the presence of NAbs was not associated with loss of efficacy. In conclusion, immunogenicity of nivolumab is not clinically meaningful. PMID- 27557787 TI - Erratum to: Strong predictive value of mannose-binding lectin levels for cardiovascular risk of hemodialysis patients. PMID- 27557788 TI - Copper-Based Metal-Organic Porous Materials for CO2 Electrocatalytic Reduction to Alcohols. AB - The electrocatalytic reduction of CO2 has been investigated using four Cu-based metal-organic porous materials supported on gas diffusion electrodes, namely, (1) HKUST-1 metal-organic framework (MOF), [Cu3 (MU6 -C9 H3 O6 )2 ]n ; (2) CuAdeAce MOF, [Cu3 (MU3 -C5 H4 N5 )2 ]n ; (3) CuDTA mesoporous metal-organic aerogel (MOA), [Cu(MU-C2 H2 N2 S2 )]n ; and (4) CuZnDTA MOA, [Cu0.6 Zn0.4 (MU-C2 H2 N2 S2 )]n . The electrodes show relatively high surface areas, accessibilities, and exposure of the Cu catalytic centers as well as favorable electrocatalytic CO2 reduction performance, that is, they have a high efficiency for the production of methanol and ethanol in the liquid phase. The maximum cumulative Faradaic efficiencies for CO2 conversion at HKUST-1-, CuAdeAce-, CuDTA-, and CuZnDTA-based electrodes are 15.9, 1.2, 6, and 9.9 %, respectively, at a current density of 10 mA cm-2 , an electrolyte-flow/area ratio of 3 mL min cm-2 , and a gas-flow/area ratio of 20 mL min cm-2 . We can correlate these observations with the structural features of the electrodes. Furthermore, HKUST-1- and CuZnDTA-based electrodes show stable electrocatalytic performance for 17 and 12 h, respectively. PMID- 27557789 TI - Fat-suppressed T2-weighted MRI appearance of subchondral insufficiency fracture of the femoral head. AB - OBJECTIVE: Our aims were to investigate the imaging appearance of subchondral insufficiency fracture (SIF) of the femoral head based on fat-suppressed T2 weighted MRI, and evaluate its correlation with the clinical outcomes following conservative treatment. MATERIALS AND METHODS: We retrospectively evaluated 40 hips in 37 patients with SIF of the femoral head (12 males and 25 females; mean age 55.8 years, range 22-78 years). MRI examinations were performed within 3 months after the onset of hip pain. Using fat-suppressed T2-weighted imaging, we evaluated the hips for the intensity of the subchondral bone (corresponding to the area superior to the low intensity band on T1-weighted images) as well as bone marrow edema, joint effusion, and presence of the band lesion. We then correlated the intensity of the subchondral bone with clinical outcomes. RESULTS: The hips were classified into three types based on subchondral intensity on fat suppressed T2-weighted images: type 1 (21 hips) showed high intensity, type 2 (eight hips) showed heterogeneous intensity, and type 3 (11 hips) showed low intensity. The mean period between pain onset and MRI examination was significantly longer for type 2 hips than for type 1. Healing rates were 86 % for type 1, 75 % for type 2, and 18 % for type 3. CONCLUSION: SIF cases were classified into three types based on subchondral intensity on fat-suppressed T2 weighted imaging performed within 3 months after pain onset. Type 3 SIF tended to be intractable to conservative treatment compared to type 1 and type 2. PMID- 27557790 TI - Capabilities of the RENEB network for research and large scale radiological and nuclear emergency situations. AB - PURPOSE: To identify and assess, among the participants in the RENEB (Realizing the European Network of Biodosimetry) project, the emergency preparedness, response capabilities and resources that can be deployed in the event of a radiological or nuclear accident/incident affecting a large number of individuals. These capabilities include available biodosimetry techniques, infrastructure, human resources (existing trained staff), financial and organizational resources (including the role of national contact points and their articulation with other stakeholders in emergency response) as well as robust quality control/assurance systems. MATERIALS AND METHODS: A survey was prepared and sent to the RENEB partners in order to acquire information about the existing, operational techniques and infrastructure in the laboratories of the different RENEB countries and to assess the capacity of response in the event of radiological or nuclear accident involving mass casualties. The survey focused on several main areas: laboratory's general information, country and staff involved in biological and physical dosimetry; retrospective assays used, the number of assays available per laboratory and other information related to biodosimetry and emergency preparedness. Following technical intercomparisons amongst RENEB members, an update of the survey was performed one year later concerning the staff and the available assays. CONCLUSIONS: The analysis of RENEB questionnaires allowed a detailed assessment of existing capacity of the RENEB network to respond to nuclear and radiological emergencies. This highlighted the key importance of international cooperation in order to guarantee an effective and timely response in the event of radiological or nuclear accidents involving a considerable number of casualties. The deployment of the scientific and technical capabilities existing within the RENEB network members seems mandatory, to help other countries with less or no capacity for biological or physical dosimetry, or countries overwhelmed in case of a radiological or nuclear accident involving a large number of individuals. PMID- 27557791 TI - Impact of weather factors on hand, foot and mouth disease, and its role in short term incidence trend forecast in Huainan City, Anhui Province. AB - Hand, foot, and mouth disease (HFMD) is one of the most common communicable diseases in China, and current climate change had been recognized as a significant contributor. Nevertheless, no reliable models have been put forward to predict the dynamics of HFMD cases based on short-term weather variations. The present study aimed to examine the association between weather factors and HFMD, and to explore the accuracy of seasonal auto-regressive integrated moving average (SARIMA) model with local weather conditions in forecasting HFMD. Weather and HFMD data from 2009 to 2014 in Huainan, China, were used. Poisson regression model combined with a distributed lag non-linear model (DLNM) was applied to examine the relationship between weather factors and HFMD. The forecasting model for HFMD was performed by using the SARIMA model. The results showed that temperature rise was significantly associated with an elevated risk of HFMD. Yet, no correlations between relative humidity, barometric pressure and rainfall, and HFMD were observed. SARIMA models with temperature variable fitted HFMD data better than the model without it (sR 2 increased, while the BIC decreased), and the SARIMA (0, 1, 1)(0, 1, 0)52 offered the best fit for HFMD data. In addition, compared with females and nursery children, males and scattered children may be more suitable for using SARIMA model to predict the number of HFMD cases and it has high precision. In conclusion, high temperature could increase the risk of contracting HFMD. SARIMA model with temperature variable can effectively improve its forecast accuracy, which can provide valuable information for the policy makers and public health to construct a best-fitting model and optimize HFMD prevention. PMID- 27557792 TI - Minimizing injury to the donor area in follicular unit extraction (FUE) harvesting. AB - BACKGROUND: Follicular Unit Extraction (FUE) is considered to be a minimally invasive procedure, and the injury to the donor area caused by a sharp punch may result in dermal fibrosis and clinically observed hypopigmentation. OBJECTIVE: To evaluate with advanced image processing the efficacy of using 0.9% normal saline in minimizing the injury to the donor area in FUE donor harvesting. PATIENTS AND METHODS: The term acute extraction (AE) is used to describe the donor harvesting technique, whereby a follicular unit (FU) is removed with a punch that is aligned parallel with the exit angle of the hair follicle. The term vertical extraction (VE) describes the technique where a FU is removed in like manner, but normal saline is injected intradermally prior to harvesting so the punch being perpendicular to the skin. Thirty-five patients were selected for this study to apply both harvesting techniques and then to compare the differences in wound surface size and skin mass removed by the punch. RESULTS: A significant reduction in the mean values of wound surface and skin mass was recorded in vertical extraction compared to those in acute extraction. CONCLUSION: The injection of normal saline prior to harvesting proved to be very efficient in minimizing skin injury in FUE harvesting. PMID- 27557794 TI - The [4Fe-4S] clusters of Rpo3 are key determinants in the post Rpo3/Rpo11 heterodimer formation of RNA polymerase in Methanosarcina acetivorans. AB - Subunits Rpo3 and Rpb3/AC40 of RNA polymerase (RNAP) from many archaea and some eukaryotes, respectively, contain a ferredoxin-like domain (FLD) predicted to bind one or two [4Fe-4S] clusters postulated to play a role in regulating the assembly of RNAP. To test this hypothesis, the two [4Fe-4S] cluster Rpo3 from Methanosarcina acetivorans was modified to generate variants that lack the FLD or each [4Fe-4S] cluster. Viability of gene replacement mutants revealed that neither the FLD nor the ability of the FLD to bind either [4Fe-4S] cluster is essential. Nevertheless, each mutant demonstrated impaired growth due to significantly lower RNAP activity when compared to wild type. Affinity purification of tagged Rpo3 variants from M. acetivorans strains revealed that neither the FLD nor each [4Fe-4S] cluster is required for the formation of a Rpo3/11 heterodimer, the first step in the assembly of RNAP. However, the association of the Rpo3/11 heterodimer with catalytic subunits Rpo2' and Rpo1" was diminished by the removal of the FLD and each cluster, with the loss of cluster 1 having a more substantial effect than the loss of cluster 2. These results reveal that the FLD and [4Fe-4S] clusters, particularly cluster 1, are key determinants in the post Rpo3/11 heterodimer assembly of RNAP in M. acetivorans. PMID- 27557795 TI - Elevated C-type natriuretic peptide elicits exercise preconditioning-induced cardioprotection against myocardial injury probably via the up-regulation of NPR B. AB - To evaluate exercise preconditioning (EP)-induced cardioprotective effects against exercise-induced acute myocardial injury and investigate the alterations of C-type natriuretic peptide (CNP) and its specific receptor, natriuretic peptide receptor B (NPR-B), during EP-induced cardioprotection. Rats were subjected to treadmill exercise as an EP model (4 periods of 10 min each at 30 m/min with intervening periods of rest lasting 10 min). High-intensity exercise was performed 0.5 and 24 h after the EP. EP attenuated high-intensity exercise induced myocardial injury in both the early and late phases. After EP and high intensity exercise, CNP and NPR-B levels increased robustly, but no alterations in the plasma CNP were observed. The enhanced NPR-B, plasma and tissue CNP, and its mRNA levels after high-intensity exercise were significantly elevated by EP. These results suggest that cardiac CNP and NPR-B play an important role in EP mediated cardioprotection against high-intensity exercise-induced myocardial injury in rats. PMID- 27557797 TI - Following My Head and My Heart: Integrating Preschoolers' Empathy, Theory of Mind, and Moral Judgments. AB - Associations among hypothetical, prototypic moral, and conventional judgments; theory of mind (ToM); empathy; and personal distress were examined in 108 socioeconomically diverse preschoolers (Mage = 42.94 months, SD = 1.42). Repeated measures analysis of covariance with empathy, false beliefs, and their interaction as covariates indicated that empathy was significantly associated with judgments of greater moral but not conventional transgression severity, particularly for psychological harm, and with deserved punishment for unfairness. False beliefs were associated with (combined) moral criterion judgments of rule and authority independence and inalterability. Empathy also was positively associated with criterion judgments but only for children low in ToM. Personal distress was unrelated to judgments. Results demonstrate the importance of both affective and cognitive processes in preschoolers' moral judgments. PMID- 27557796 TI - The role of bone void fillers in medial opening wedge high tibial osteotomy: a systematic review. AB - PURPOSE: A variety of bone void filling materials and methods are available in opening medial wedge HTO (OWHTO). The pertinent question revolves around if and when bone void fillers are needed. The primary purpose of this study was to systematically review outcomes and complications after OWHTO with and without the use of bone void fillers. METHODS: The EMBASE, PubMed?MEDLINE, Cochrane Library and Google Scholar databases were searched to identify articles that reported OWHTO results using different bone void fillers until March 2016. Only articles reporting the exact bone void filler type, the opening gap size and the fixation method were included. The extracted data included the study design, demographic data, the radiological and clinical results and complication rates. Outcomes were analysed with regard to bone void filler type, and comparison was made between the groups (allograft, autograft, synthetic bone void filler and OWHTO without bone void filling). RESULTS: Twenty-two articles reporting the results of 1421 OWHTO met the inclusion criteria. In total, 647 osteotomies were completed with allogeneic graft as bone void filler, 367 with synthetic materials, 199 with autograft and 208 without any bone void filling material. The maximum opening gap size was similar in all groups with mean of 9.8 mm (range 4-17.5 mm). Locking plate fixation was used in 90 % of the osteotomies that were completed without bone void filler, while all allograft cases and more then 90 % of the autograft cases were done with non-locking systems. The highest rates of non-union (1.1 %) were seen in the synthetic group, compared to 0.5 % in the all the other groups. CONCLUSIONS: This systematic review showed no definitive advantages for OWHTO with any bone void filler in terms of union rates and loss of correction. Moreover, the use of autografts or allografts showed more favourable outcomes than synthetic bone substitutes. OWHTO with gaps smaller then 10 mm and rigid fixation might be successfully managed without bone grafting. However, when bone grafting is needed, autograft bone provides higher rates of clinical and radiographic union. The use of synthetic bone substitutes in OWHTO cannot be recommended. LEVEL OF EVIDENCE: III. PMID- 27557798 TI - Gain-loss asymmetry in neural correlates of temporal discounting: An approach avoidance motivation perspective. AB - Gain-loss asymmetry in temporal discounting (i.e., when individuals discount gains more than losses) has been implicated in numerous problematic and addictive behaviors, resulting in enormous personal and societal costs. On the basis of findings from a previous study, we speculated that approach-avoidance motivation would modulate gain-loss asymmetry. To test this speculation, we examined the effects of motivation on gain-loss asymmetry by analyzing functional connectivity. We found that approach and avoidance motivation were negatively associated with functional connectivity between the medial orbitofrontal cortex (MOFC) and the dorsolateral prefrontal cortex and functional connectivity between the MOFC and the posterior parietal cortex (PPC) in the gain domain. Only avoidance motivation was found to be positively associated with functional connectivity between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) as well as between the MPFC and the insula in the loss domain. Our findings suggest that the relationships of approach-avoidance motivation and neural correlates yielded an asymmetrical pattern between the gain and loss domains in temporal discounting. Thus, we provide new insight into understanding gain-loss asymmetry in temporal discounting. PMID- 27557799 TI - Corrigendum: Analysis of the genes responsible for steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis in Japanese patients by whole exome sequencing analysis. PMID- 27557800 TI - A strategy to discover new organizers identifies a putative heart organizer. AB - Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development. PMID- 27557801 TI - Exploring lifestyle and risk in preventing type 2 diabetes-a nested qualitative study of older participants in a lifestyle intervention program (VEND-RISK). AB - BACKGROUND: Lifestyle intervention may reduce the development of type 2 diabetes among high-risk individuals. The aim of this study was to explore how older adults perceived their own lifestyle and being at increased risk for type 2 diabetes while they participated in a lifestyle intervention programme. METHODS: A nested qualitative study was performed with 26 participants (mean age 68 years) in the VEND-RISK Study. Participants had previously participated in the HUNT3 Study and the HUNT DE-PLAN Study, where their risk for developing type 2 diabetes (FIND-RISC >= 15) had been identified. The data were analysed using systematic text condensation. RESULTS: Two main themes were identified. The first theme was having resources available for an active lifestyle, which included having a family and being part of a social network, having a positive attitude toward life, and maintaining established habits from childhood to the present. The second theme was being at increased risk for type 2 diabetes, which included varied reactions to the information on increased risk, how lifestyle intervention raised awareness about risk behaviour, and health-related worries and ambitions as type 2 diabetes prevention. CONCLUSIONS: Assessing a participant's resources could improve the outcomes of lifestyle intervention programmes. Both family history and risk perception could be used in preventive strategies to enhance changes in lifestyle. TRIAL REGISTRATION: The VEND-RISK Study was registered in ClinicalTrials.gov on April 26, 2010, with the registration number NCT01135901 . PMID- 27557802 TI - The interactive association of smoking and drinking levels with presence of periodontitis in South Korean adults. AB - BACKGROUND: Periodontitis is a chronic and long-lasting low-grade inflammatory disease. Numerous studies have shown that the severity of periodontitis rose when there was an increase in the amount of smoking or alcohol consumption. However, as periodontitis known as a chronic disease, it is important to consider not only the amount but "duration" with frequency i.e., rates, of smoking or drinking. This study assessed impacts of the amount and duration of smoking and drinking on periodontal health in Korean adults. We also investigated whether or not there is an interactive effect of smoking and drinking on periodontal health. METHODS: Under a cross-sectional study design, we used data from the fourth and fifth the Korean National Health and Nutrition Examination Survey (KNHANES) sessions (2008 2010). A total of 18,488 subjects (over 19 years) answered both smoking and drinking status and were given the periodontal examination. Periodontal health status was determined by the community periodontal index (CPI) developed by the World Health Organization (WHO). According to the WHO guidelines, if a participant's CPI was 3 or larger, we classified the person as a case of periodontitis. Participants with a CPI < 3 were assigned to the control group. RESULTS: Prevalence of periodontitis for self-reported smokers or drinkers in South Korea was 35.0 or 28.0 %, respectively. We observed 1.20 (0.93~1.56) of odds ratio (95 % CI) for prevalence (POR) of periodontitis for those smoked <13 pack-year (PY) and drank >=6.8 glass-year (GY). And we had POR of 1.91 (1.34~2.73) for those smoked >=13 PY and drank <6.8 GY, compared to those nonsmoking nondrinkers. The observed POR of 2.41 (95 % CI: 1.94-3.00), for those smoked >=13 PY and drank >=6.8 GY, was higher than a multiplicative effect estimated, i.e., 1.20 (0.93~1.56) [those smoked <13 PY and drank >=6.8 GY] * 1.91 (1.34~2.73) [those smoked >=13 PY and drank <6.8 GY], or 2.29. CONCLUSIONS: We observed a multiplicative interactive effect of smoking and drinking on periodontal status among Korean adults. PMID- 27557803 TI - Long distance seawater intrusion through a karst conduit network in the Woodville Karst Plain, Florida. AB - Five periods of increased electrical conductivity have been found in the karst conduits supplying one of the largest first magnitude springs in Florida with water. Numerous well-developed conduit networks are distributed in the Woodville Karst Plain (WKP), Florida and connected to the Gulf of Mexico. A composite analysis of precipitation and electrical conductivity data provides strong evidence that the increases in conductivity are directly tied to seawater intrusion moving inland and traveling 11 miles against the prevailing regional hydraulic gradient from from Spring Creek Spring Complex (SCSC), a group of submarine springs at the Gulf Coast. A geochemical analysis of samples from the spring vent rules out anthropogenic contamination and upwelling regional recharge from the deep aquifer as sources of the rising conductivity. The interpretation is supported by the conceptual model established by prior researchers working to characterize the study area. This paper documents the first and longest case of seawater intrusion in the WKP, and also indicates significant possibility of seawater contamination through subsurface conduit networks in a coastal karst aquifer. PMID- 27557804 TI - Herpes simplex encephalitis in an immunocompromised adult with novel MRI and pathology findings. PMID- 27557805 TI - Leukocytoclastic vasculitis following lenalidomide during the treatment of follicular lymphoma. PMID- 27557807 TI - High-level language ability in healthy individuals and its relationship with verbal working memory. AB - The aims of the study were to investigate healthy subjects' performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20 79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegard, Hartelius, & Ahlsen, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL. PMID- 27557806 TI - Markov chain Monte Carlo and expectation maximization approaches for estimation of haplotype frequencies for multiply infected human blood samples. AB - BACKGROUND: Haplotypes are important in anti-malarial drug resistance because genes encoding drug resistance may accumulate mutations at several codons in the same gene, each mutation increasing the level of drug resistance and, possibly, reducing the metabolic costs of previous mutation. Patients often have two or more haplotypes in their blood sample which may make it impossible to identify exactly which haplotypes they carry, and hence to measure the type and frequency of resistant haplotypes in the malaria population. RESULTS: This study presents two novel statistical methods expectation-maximization (EM) and Markov chain Monte Carlo (MCMC) algorithms to investigate this issue. The performance of the algorithms is evaluated on simulated datasets consisting of patient blood characterized by their multiplicity of infection (MOI) and malaria genotype. The datasets are generated using different resistance allele frequencies (RAF) at each single nucleotide polymorphisms (SNPs) and different limit of detection (LoD) of the SNPs and the MOI. The EM and the MCMC algorithm are validated and appear more accurate, faster and slightly less affected by LoD of the SNPs and the MOI compared to previous related statistical approaches. CONCLUSIONS: The EM and the MCMC algorithms perform well when analysing malaria genetic data obtained from infected human blood samples. The results are robust to genotyping errors caused by LoDs and function well even in the absence of MOI data on individual patients. PMID- 27557808 TI - The role of visual stimuli on standing posture in children with bilateral cerebral palsy. AB - BACKGROUND: In children with bilateral cerebral palsy (CP) maintaining a standing position can be difficult. The fundamental motor task of standing independently is achieved by an interaction between the visual, somatosensory, and vestibular systems. In CP, the motor disorders are commonly accompanied by sensory and perceptual disturbances. Our aims were to examine the influence of visual stimuli on standing posture in relation to standing ability. METHODS: Three dimensional motion analysis with surface electromyography was recorded to describe body position, body movement, and muscle activity during three standing tasks: in a self-selected position, while blindfolded, and during an attention-demanding task. Participants were twenty-seven typically-developing (TD) children and 36 children with bilateral CP, of which 17 required support for standing (CP-SwS) and 19 stood without support (CP-SwoS). RESULTS: All children with CP stood with a more flexed body position than the TD children, even more pronounced in the children in CP-SwS. While blindfolded, the CP-SwS group further flexed their hips and knees, and increased muscle activity in knee extensors. In contrast, the children in CP-SwoS maintained the same body position but increased calf muscle activity. During the attention-demanding task, the children in CP-SwoS stood with more still head and knee positions and with less muscle activity. CONCLUSIONS: Visual input was important for children with CP to maintain a standing position. Without visual input the children who required support dropped into a further crouched position. The somatosensory and vestibular systems alone could not provide enough information about the body position in space without visual cues as a reference frame. In the children who stood without support, an intensified visual stimulus enhanced the ability to maintain a quiet standing position. It may be that impairments in the sensory systems are major contributors to the difficulties to stand erect in children with CP. PMID- 27557809 TI - Antibody Engineering & Therapeutics 2016: The Antibody Society's annual meeting, December 11-15, 2016, San Diego, CA. AB - Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement. The meeting will open with keynote speakers Dennis R. Burton (The Scripps Research Institute), who will review progress toward a neutralizing antibody-based HIV vaccine; Olivera J. Finn, (University of Pittsburgh School of Medicine), who will discuss prophylactic cancer vaccines as a source of therapeutic antibodies; and Paul Richardson (Dana Farber Cancer Institute), who will provide a clinical update on daratumumab for multiple myeloma. In a featured presentation, a representative of the World Health Organization's INN expert group will provide a perspective on antibody naming. "Antibodies to watch in 2017" and progress on The Antibody Society's 2016 initiatives will be presented during the Society's special session. In addition, two pre-conference workshops covering ways to accelerate antibody drugs to the clinic and the applications of next-generation sequencing in antibody discovery and engineering will be held on Sunday December 11, 2016. PMID- 27557810 TI - Favorable outcome of Epstein-Barr virus-associated B-cell lymphoproliferative disorder complicated by immunoglobulin G4-related disease treated with rituximab based therapy: a case report. AB - BACKGROUND: After acute infection of Epstein-Barr virus, Epstein-Barr virus infected B cells survive but usually do not show clonal proliferation. However, Epstein-Barr virus-infected B cells occasionally acquire a proliferative capacity that provokes clonal lymphoproliferative disorders. We herein present a case with Epstein-Barr virus-infected CD30+ B cell and immunoglobulin G4+ plasmacytoid cell proliferation in the lymph nodes, suggesting a pathological and clinical interaction between Epstein-Barr virus-associated B-cell lymphoproliferative disorders and immunoglobulin G4-related disease. Immunoglobulin G4-related disease has been recognized as a benign disease with proliferation of IgG4 related disease+ plasmacytoid cells. Several studies have recently reported the coexistence of immunoglobulin G4-related disease+ plasmacytoid cells with Epstein Barr virus-infected B cells in lymph nodes in some immunoglobulin G4-related disease cases. However, the pathogenic role of the clonal proliferation of Epstein-Barr virus-infected B cells in immunoglobulin G4-related disease, as well as the treatments for patients with both Epstein-Barr virus-infected B cells and immunoglobulin G4-related disease, have never been discussed. CASE PRESENTATION: A 50-year-old Japanese man was referred to us for persistent fatigue and lymphadenopathy. His blood examination showed elevated IgG4, and detected high levels of Epstein-Barr virus DNA. A lymph node biopsy revealed IgG4+ plasmacytoid cells and infiltration of large lymphoid cells, which were positive for CD20, CD30, Epstein-Barr virus-related late membrane protein 1, and Epstein-Barr virus encoded RNA, and were negative for IgG4. Based on the diagnosis of both Epstein Barr virus-associated B-cell lymphoproliferative disorder and IgG4-related disease, the patient received eight cycles of rituximab combined with cyclophosphamide and prednisolone, which resulted in the complete disappearance of lymphadenopathy. Moreover, his serum IgG4 level was significantly reduced, and plasma Epstein-Barr virus DNA became undetectable. Although prednisolone was transiently administered in each cycle of immunochemotherapy, the therapeutic effect has persisted for Epstein-Barr virus-associated B-cell lymphoproliferative disorder and IgG4-related disease as of 1 year after finishing treatment. CONCLUSIONS: In the present case, clinical presentation and pathological findings revealed that Epstein-Barr virus-associated B-cell lymphoproliferative disorder coexisted with IgG4-related disease. Although several studies have described the relationship between Epstein-Barr virus-infected B cells and IgG4-related disease, this is the first report of a patient whose plasma Epstein-Barr virus DNA level, which correlated with the disease statuses of both diseases, was monitored. Moreover, rituximab-based immunochemotherapy was highly effective for both diseases. Our findings are suggestive for establishing a novel treatment strategy for IgG4-related disorders associated with chronic Epstein-Barr virus infection. PMID- 27557811 TI - Novel PEX3 Gene Mutations Resulting in a Moderate Zellweger Spectrum Disorder. AB - BACKGROUND: Peroxisome biogenesis disorders (PBDs) may have a variable clinical expression, ranging from severe, lethal to mild phenotypes with progressive evolution. PBDs are autosomal recessive disorders caused by mutations in PEX genes, which encode proteins called peroxins, involved in the assembly of the peroxisome. Patient Description: We herein report a patient who is currently 9 years old and who is compound heterozygous for two novel mutations in the PEX3 gene. RESULTS: Mild biochemical abnormalities of the peroxisomal parameters suggested a Zellweger spectrum defect in the patient. Sequence analysis of the PEX3 gene identified two novel heterozygous, pathogenic mutations. CONCLUSION: Mutations in PEX3 usually result in a severe, early lethal phenotype. We report a patient compound heterozygous for two novel mutations in the PEX3 gene, who is less affected than previously reported patients with a defect in the PEX3 gene. Our findings indicate that PEX3 defects may cause a disease spectrum similar as previously observed for other PEX gene defects. PMID- 27557812 TI - Delayed Infusion Reactions to Enzyme Replacement Therapies. AB - BACKGROUND: There are currently ten intravenous enzyme replacement therapy (ERT) products available for the treatment of eight different lysosomal diseases (LD) in the USA. Additional ERT products are in clinical trials. The most common ERT adverse events are infusion reactions (IR). While IR are often defined as hypersensitivity or anaphylactoid reactions occurring concurrently with (i.e., during) infusion administration (CIR), there exists the potential for delayed infusion reactions (DIR), which present after completion of infusion administration. HYPOTHESIS: Concurrent infusion reactions (CIR) are not the only infusion reactions associated with enzyme therapy. METHODS: This study evaluated the occurrence of infusion reactions in 46 patients with LD who had received ERT for a minimum of 2 years. Infusion reactions were evaluated according to symptoms, time of onset, and duration of reactions. The frequency of infusion reactions with each ERT product was compared to that reported in the FDA-approved product package insert. RESULTS AND CONCLUSIONS: In this study, DIR were observed and occurred as often as CIR in the study population, despite not being characterized or reported in most ERT product package inserts. Effective methods for managing DIR and CIR differed, thus emphasizing the importance of monitoring for both types of infusion reactions in order to optimize outcomes for patients using ERT. PMID- 27557813 TI - Physical activity and relaxation in the work setting to reduce the need for recovery: what works for whom? AB - BACKGROUND: To recover from work stress, a worksite health program aimed at improving physical activity and relaxation may be valuable. However, not every program is effective for all participants, as would be expected within a "one size fits all" approach. The effectiveness of how the program is delivered may differ across individuals. The aim of this study was to identify subgroups for whom one intervention may be better suited than another by using a new method called QUalitative INteraction Trees (QUINT). METHODS: Data were used from the "Be Active & Relax" study, in which 329 office workers participated. Two delivery modes of a worksite health program were given, a social environmental intervention (group motivational interviewing delivered by team leaders) and a physical environmental intervention (environmental modifications). The main outcome was change in Need for Recovery (NFR) from baseline to 12 month follow up. The QUINT method was used to identify subgroups that benefitted more from either type of delivery mode, by incorporating moderator variables concerning sociodemographic, health, home, and work-related characteristics of the participants. RESULTS: The mean improvement in NFR of younger office workers in the social environmental intervention group was significantly higher than younger office workers who did not receive the social environmental intervention (10.52; 95 % CI: 4.12, 16.92). Furthermore, the mean improvement in NFR of older office workers in the social environmental intervention group was significantly lower than older office workers who did not receive the social environmental intervention ( -10.65; 95 % CI: -19.35, -1.96). The results for the physical environmental intervention indicated that the mean improvement in NFR of office workers (regardless of age) who worked fewer hours overtime was significantly higher when they had received the physical environmental intervention than when they had not received this type of intervention (7.40; 95 % CI: 0.99, 13.81). Finally, for office workers who worked more hours overtime there was no effect of the physical environmental intervention. CONCLUSIONS: The results suggest that a social environmental intervention might be more beneficial for younger workers, and a physical environmental intervention might be more beneficial for employees with a few hours overtime to reduce the NFR. TRIAL REGISTRATION: NTR2553. PMID- 27557814 TI - Mapping the Technological Knowledge Landscape: The Case of Epigenetics. AB - BACKGROUND: Epigenetics is a biomedical novelty in drug design and disease control whose mechanisms play a significant role in transferring environmental signals to determine patterns of gene expression. Systematic identification of the main trends in epigenetics patenting activity provides insights into fundamental building blocks of this research field and policy guidance to funding agencies. OBJECTIVE: The review aims at providing a comprehensive overview of the research and development trend in epigenetics by mapping the knowledge structure in patent landscape. METHODS: Citation-based patent network analysis was performed to visualize the technological landscape. We focus on identifying the structure of the knowledge networks to study the technological trajectories. Patents that play an integral part in the dissemination and bridging of the technical knowledge are located and ranked. The latent topics in patent documents are highlighted by means of a topic modeling technique. RESULTS: Visualization of the patent network results in four main clusters. The first two clusters deal with the inhibition of histone deacetylase (HDAC). The third cluster covers inventions related to DNA methylation, which represents an epigenetic signaling tool that cells use to control gene expression. The fourth cluster encompasses computing systems and data mining techniques for identifying combinations of genetic and epigenetic attributes related to health and lifestyle improvements. CONCLUSION: We are in the growth period of gathering knowledge on various mechanisms of epigenetic regulation. There is enormous potential for improving healthcare through better understanding of the interrelationships between epigenetic control of gene expression and compounds that trigger these modifications. PMID- 27557815 TI - Evidence of the presence of the Zika virus in Mexico since early 2015. AB - To assess the possible circulation of Zika virus (ZIKV) prior to the first documented case in Mexico, we reanalyzed the stored samples from the states of Veracruz and Yucatan, which were originally collected to test for dengue (DENV) and chikungunya (CHIKV) but were negative for these viruses despite the symptomatology. The samples were originally collected between the 30 and 46 epidemiological weeks (EW) when the ZIKV was not yet declared as a Public Health Emergency of International Concern (PHEIC). From the total 4016 negative samples, a total of one hundred samples, 50 from Veracruz (CHIK- DENV-) and 50 from Yucatan (4 CHIK- DENV- and 46 CHIK- or DENV-), were tested for Zika virus by using RT-PCR. Results showed that in Veracruz and Yucatan, 20 % (10/50) and 70 % (35/50) were, respectively, ZIKV positive, indicating unequivocally the presence of ZIKV at least since July 2015. We also tested non-confirmed suspect measles cases from early 2015 for ZIKV by RT-PCR. Remarkably in 11 Mexican states, 86 % (18/21) were positive with the earlier symptoms onset as early as May 2015. Finally, RT-PCR analyses on RNA extracted from Aedes aegypti mosquitoes captured from January to March 2015 showed the presence of ZIKV, strongly suggesting that the vector was already carrying the virus at the start of 2015. PMID- 27557816 TI - Hsp90 inhibitor reduces porcine circovirus 2 replication in the porcine monocytic line 3D4/31. AB - Porcine circovirus 2 (PCV2) is an important pathogen of swine, which causes porcine circovirus disease and porcine circovirus-associated diseases (PCVD/PCVAD). However, no effective countermeasures exist to combat this virus infection so far. Recently, heat shock protein 90 (Hsp90) was found to be an important host factor for the replication of multiple viruses and the inhibition of Hsp90 showed significant antiviral effects. Inhibition of Hsp90 by treatment of porcine monocytic line 3D4/31 with geldanamycin (GA), a specific inhibitor of Hsp90, caused a 70 % decrease in viral Cap protein expression. Further, individual knockdown targeting Hsp90alpha or Hsp90beta with siRNAs resulted in down to 20-25 % of decrease in viral replication, and inhibited the PCV2 titer by approximately 12- and 15-fold, respectively. In addition, we investigated alteration of several cytokine production in PCV2-infected cells following treatment with GA. Then, we found that GA could decrease IL-1beta, IL-6, and IL 12p40 mRNA levels, respectively, by 30, 40, and 40 % in PCV2-infected cells. Our results shed light on the possibility of developing potential therapeutics targeting Hsp90 against PCV2 infection. PMID- 27557818 TI - An applet for the Gabor similarity scaling of the differences between complex stimuli. AB - It is widely accepted that after the first cortical visual area, V1, a series of stages achieves a representation of complex shapes, such as faces and objects, so that they can be understood and recognized. A major challenge for the study of complex shape perception has been the lack of a principled basis for scaling of the physical differences between stimuli so that their similarity can be specified, unconfounded by early-stage differences. Without the specification of such similarities, it is difficult to make sound inferences about the contributions of later stages to neural activity or psychophysical performance. A Web-based app is described that is based on the Malsburg Gabor-jet model (Lades et al., 1993), which allows easy specification of the V1 similarity of pairs of stimuli, no matter how intricate. The model predicts the psycho physical discriminability of metrically varying faces and complex blobs almost perfectly (Yue, Biederman, Mangini, von der Malsburg, & Amir, 2012), and serves as the input stage of a large family of contemporary neurocomputational models of vision. PMID- 27557817 TI - Dietary patterns in an elderly population and their relation with bone mineral density: the Rotterdam Study. AB - PURPOSE: Our aim was to identify dietary patterns that are associated with bone mineral density (BMD) against a background of relatively high dairy intake in elderly Dutch subjects. METHODS: Participants were 55 years of age and older (n = 5144) who were enrolled in The Rotterdam Study, a population-based prospective cohort study. Baseline intake of 28 pre-defined food groups was determined using a validated food frequency questionnaire. Dietary patterns were identified using principal component analysis. BMD was measured using dual-energy X-ray absorptiometry at baseline and at three subsequent visits (between 1993 and 2004). Linear mixed modelling was used to longitudinally analyse associations of adherence to each pattern with repeatedly measured BMD (both in Z scores). RESULTS: After adjustment for confounders, two dietary patterns were associated with high BMD: a "Traditional" pattern, characterized by high intake of potatoes, meat and fat (beta = 0.06; 95 % CI 0.03, 0.09) and a "Health conscious" pattern, characterized by high intake of fruits, vegetables, poultry and fish (beta = 0.06; 95 % CI 0.04, 0.08). The "Processed" pattern, characterized by high intake of processed meat and alcohol, was associated with low BMD (beta = -0.03; 95 % CI -0.06, -0.01). Associations of adherence to the "Health conscious" and "Processed" pattern with BMD were independent of body weight and height, whereas the association between adherence to the "Traditional" pattern with BMD was not. CONCLUSIONS: Against a background of high dairy intake and independent of anthropometrics, a "Health conscious" dietary pattern may have benefits for BMD, whereas a "Processed" dietary pattern may pose a risk for low BMD. PMID- 27557819 TI - A Review on Plasmodium falciparum-Protein Farnesyltransferase Inhibitors as Antimalarial Drug Targets. AB - BACKGROUND: Protein farnesyltransferase (PFT) inhibitors have emerged as a potent target for the malaria treatment caused by the Plasmodium falciparum (Pf) parasite. OBJECTIVE: To explore the various scaffolds which are active against Pf PFT target. RESULT: Seven inhibitor scaffolds based on ethylenediamine, peptidomimetic, benzophenone, benzamide, tetrahydroquinoline, naphthyridine and oxy-tetrahydroquinoline, have been developed till date. CONCLUSION: It is concluded that naphthyridine based drugs are the most promising one. Furthermore, introducing the hydrophobic molecules like isoprenyl groups to a protein or a chemical compound facilitate protein-protein and protein-membrane interactions thereby makes them good candidates as new therapeutics. The future research should focus on the disease rather than the infection and the dynamics of its transmission; this will bring a new vision about the disease. PMID- 27557820 TI - PHB in Cardiovascular and Other Diseases: Present Knowledge and Implications. AB - BACKGROUND: Prohibitin (PHB) is overtly conserved evolutionarily and ubiquitously expressed protein with pleiotropic functions in diverse cellular compartments. However, regulation and function of these proteins in different cells, tissues and in various diseases is different as evidenced by expression of these proteins which is found to be reduced in heart diseases, kidney diseases, lung disease, Crohn's disease and ulcerative colitis but this protein is highly expressed in diverse cancers. The mechanism by which this protein acts at the molecular level in different subcellular localizations or in different cells or tissues in different conditions (diseases or normal) has remained poorly understood. There are several studies reported to understand and decipher PHB's role in diseases and/or cancers of ovary, lung, stomach, thyroid, liver, blood, prostrate, gastric, esophagus, glioma, breast, bladder etc. where PHB is shown to act through mechanisms by acting as oncogene, tumor suppressor, antioxidant, antiapoptotic, in angiogenesis, autophagy etc. OBJECTIVE: This review specifically gives attention to the functional role and regulatory mechanism of PHB proteins in cardiovascular health and diseases and its associated implications. Various molecular pathways involved in PHB function and its regulation are analyzed. CONCLUSION: PHB is rapidly emerging as a critical target molecule for cardiovascular signaling. Progress in delineating CVD and mechanisms of PHB in diverse molecular pathways is essential for determining when and how PHB targeted therapy might be feasible. In this regard, new therapies targeting PHB may best be applied in the future together with molecular profiling of CVD for clinical stratification of disease diagnosis and prognosis. PMID- 27557821 TI - Clinical factors associated with lithium response in bipolar disorders. AB - BACKGROUND: Bipolar disorder is a common chronic illness characterized by high levels of morbidity and all-cause mortality. Lithium is one of the gold standard mood stabilizer treatments, but the identification of good, partial and non responders in clinical settings is inconsistent. METHODS: We used an established rating scale (the Alda scale) to classify the degree of lithium response (good response, partial response, non-response) in a large, multicentre clinically representative sample of well-characterized cases of bipolar disorders I and II. Next, we examined previously reported clinical predictors of response to determine which factors significantly differentiated between the three response groups. RESULTS: Of 754 cases, 300 received lithium, for at least 6 months, as a treatment for bipolar disorder (40%). Of these cases, 17% were classified as good response, 52% as partial response and 31% as non-response. Lifetime history of mixed episodes ( p = 0.017) and alcohol use disorders ( p = 0.015) both occurred in >20% of partial response and non-response groups but <10% of good response cases. Family history of bipolar disorder I was of borderline statistical significance, being more frequent in the good response group (38%) compared with the non-response group (18%). There was a trend ( p = 0.06) for bipolar disorder II to be associated with non-response. CONCLUSIONS: Only three factors previously identified as predictors of lithium response significantly differentiated the response groups identified in our sample. Interestingly, these factors have all been found to co-occur more often than expected by chance, and it can be hypothesized that they may represent a shared underlying factor or dimension. Further prospective studies of predictors and the performance of the Alda scale are recommended. PMID- 27557822 TI - Clinical Effectiveness, Safety Profile, and Pharmacokinetics of Daptomycin in Pediatric Patients: A Systematic Review. AB - Infections by Gram-positive pathogens pose a public health risk, especially due to increasing antibiotic resistance. Daptomycin has efficacy against most clinically important Gram-positive bacteria. Although experience regarding use of daptomycin in adults is increasing, studies on pediatric populations are limited. We aimed to evaluate the efficacy, safety, and pharmacokinetics of daptomycin in pediatric settings. We searched MEDLINE and Clinicaltrials.gov (through April 2016) and included 29 original studies in the final analysis. Available evidence suggests that daptomycin in pediatric patients has a favorable safety and tolerability profile and is an efficacious alternative for treatment of Gram positive bacteremia, endocarditis, and infections of the skin, soft tissues, joints, and bones, especially when resistant strains are involved. However, future studies need to address several issues to determine the optimal dose and various pharmacokinetic parameters in different pediatric age groups. PMID- 27557823 TI - In defence of high-speed memory scanning. AB - This paper reviews some of the evidence that bears on the existence of a mental high-speed serial exhaustive scanning process (SES) used by humans to interrogate the active memory of a set of items to determine whether it contains a test item. First proposed in the 1960s, based on patterns of reaction times (RTs), numerous later studies supported, elaborated, extended, and limited the generality of SES, while critics claimed that SES never occurred, that predictions from SES were violated, and that other mechanisms produced the RT patterns that led to the idea. I show that some of these claims result from ignoring variations in experimental procedure that produce superficially similar but quantitatively different RT patterns and that, for the original procedures, the most frequently repeated claims that predictions are violated are false. I also discuss evidence against the generality of competing theories of active-memory interrogation, especially those that depend on discrimination of directly accessible "memory strength". Some of this evidence has been available since the 1960s but has been ignored by some proponents of alternative theories. Other evidence presented herein is derived from results of one relevant experiment described for the first time, results of another described in more detail than heretofore, and new analyses of old data. Knowledge of brain function acquired during the past half century has increased the plausibility of SES. THE CONCLUSION: SES is alive and well, but many associated puzzles merit further investigation, suggestions for which are offered. PMID- 27557824 TI - Psychologists' Perspectives on Therapy Termination and the Use of Therapy Engagement/Retention Strategies. AB - : Practicing psychologists (n = 269) were surveyed regarding their perspectives on client reasons for termination at different points in therapy and their use of strategies to engage and retain clients in therapy. Psychologists estimated that one-third of their caseload unilaterally terminated (M = 13% before the third therapy session; M = 20% after the third session). They viewed lack of readiness for change/insufficient motivation as the most important barrier to early treatment engagement, and symptom improvement as the most important reason for clients' unilateral decisions to end therapy after the third session. Most psychologists reported occasional use of the majority of engagement and retention strategies. Although some strategies were used by most psychologists (e.g., building the early working alliance), fewer than 25% of psychologists reported the frequent use of time-limited treatment, appointment reminders or case management procedures. As the implementation of these strategies in clinical practice has the potential to greatly influence client retention rates, future research should examine psychologists' perspectives on and barriers to using these strategies. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Therapists tend to underestimate the number of clients who make unilateral decisions to end treatment in their own practices. Therapists are unlikely to take steps to engage and retain clients in treatment unless they believe that unilateral termination is a significant problem. Clients who unilaterally end treatment are often experiencing problems with the process of therapy (e.g., dissatisfaction, lack of fit, feeling as though therapy is going nowhere), whereas therapists often attribute failed therapy to clients. It is important to be aware of this tendency and look for other explanations. It is worthwhile to actively solicit clients' barriers in an effort to mitigate them. The empirical literature provides ample evidence that it is helpful for therapists to deliberately employ strategies to engage and retain clients in therapy. All therapists would benefit from considering which strategies fit with their practices. Although almost all therapists emphasize building the early working alliance, and this is essential to good outcome, other evidence-based methods of engaging clients in therapy are largely underutilized, such as systematically monitoring client progress and barriers, placing time limits on treatment, using appointment reminders, and case management. PMID- 27557825 TI - Employees' Perceptions of Social Norms as a Result of Implementing the Participatory Approach at Supervisor Level: Results of a Randomized Controlled Trial. AB - : Purpose A multifaceted implementation strategy was targeted at supervisors to encourage them to apply a participatory approach (PA) in dealing with employees' work functioning problems due to health concerns. This paper assesses the effect on employees' perceived social norms regarding the use of the PA to deal with work functioning problems. Methods Three organizations participated in a cluster randomized controlled trial, with randomization at the department level. Supervisors in the PA intervention departments received the implementation strategy consisting of a working group meeting, supervisor training, and optional coaching. Supervisors in the control departments received written information about the PA only. In two of the organizations, employees were invited to complete surveys at baseline and at 6-month follow-up. The primary outcome was perceived social norms regarding the use of the PA to deal with work functioning problems. Secondary measures included attitudes and self-efficacy, and intention regarding joint problem solving, and sick leave data. Effects were analyzed using multilevel analyses to account for nesting of cases. Results At baseline, 273 employees participated in the survey, with follow-up analyses of 174 employees. There were no statistically significant group effects on employee outcome measures. The intervention group showed a larger reduction in mean sick days (from 4.6 to 2.4 days) versus the control group (from 3.8 to 3.6 days), but this difference did not reach statistical significance (p > .05). Conclusion The multifaceted strategy to implement the participatory approach for supervisors did not show effects on outcomes at the employee level. To gain significant effects at the employee level, may require that an implementation strategy not only targets management and supervisors, but also employees themselves. TRIAL REGISTRATION: NTR3733. PMID- 27557827 TI - Axillary Ultrasound: For All, for None, to Diagnose Positive Nodes, or to Support Avoiding Sentinel Lymph Node Biopsy Altogether. AB - Axillary ultrasound is increasingly utilized for nodal staging preoperatively in patients presenting with invasive breast cancer to provide guidance for preoperative chemotherapy or proceeding directly to surgery. Improvements in ultrasound technology make it possible to assess the nodal burden in order to identify those patients not eligible for ACOSOG Z0011 management. However, its ability to detect metastasis is variable and dependent on operator's skills, size of metastatic deposit, and primary tumor histology subtype. Therefore, sentinel lymph node biopsy is still performed with a normal axillary ultrasound. Current debate questions whether there is a benefit to diagnosing metastasis with ultrasound-guided needle biopsy as this may lead to more axillary node dissections in an era of its decreasing role. In node-positive patients, axillary ultrasound has been preliminarily shown to be helpful in assessing nodal response after preoperative chemotherapy and improve the accuracy of sentinel node dissection which may spare future patients' axillary node dissection. Improvements in axillary ultrasound and other imaging modalities along with predictive models based on tumor biology may make axillary surgery a procedure of the past for many breast cancer patients. PMID- 27557828 TI - Adjuvant Radiotherapy in Early-Stage Breast Cancer: Evidence-Based Options. AB - BACKGROUND: Patients with a diagnosis of early-stage breast cancer are offered the option of either mastectomy or breast-conserving therapy (BCT) secondary to multiple randomized trials demonstrating equivalent long-term outcomes. Traditionally, BCT has used standard whole-breast irradiation (SWBI) after breast conserving surgery, although several alternatives have emerged during the past few decades. METHODS: This report reviews key studies supporting each radiation technique and its respective eligibility criteria to assist clinicians in deciding which adjuvant radiotherapy options are appropriate for their patients. RESULTS: In the past, completion of SWBI required 5-7 weeks of daily treatments. During the past two decades, alternatives to SWBI have emerged including hypofractionated whole-breast irradiation (3-4 weeks), accelerated partial-breast irradiation (1-3 weeks), and endocrine therapy alone. Multiple randomized trials have established the equivalence of these alternative strategies to SWBI for appropriately selected patients. Additionally, the current guidelines for patient selection demonstrate a large amount of overlap in the selection criteria for each technique. CONCLUSION: Clinicians must evaluate patient and pathologic criteria and engage in informed discussions with patients when determining which adjuvant radiation techniques are appropriate. Future strategies being explored include using tumor genetics to identify low-risk patients and switching from paradigms that omit radiotherapy to those that omit endocrine therapy. PMID- 27557826 TI - Animal Mitochondrial DNA as We Do Not Know It: mt-Genome Organization and Evolution in Nonbilaterian Lineages. AB - Animal mitochondrial DNA (mtDNA) is commonly described as a small, circular molecule that is conserved in size, gene content, and organization. Data collected in the last decade have challenged this view by revealing considerable diversity in animal mitochondrial genome organization. Much of this diversity has been found in nonbilaterian animals (phyla Cnidaria, Ctenophora, Placozoa, and Porifera), which, from a phylogenetic perspective, form the main branches of the animal tree along with Bilateria. Within these groups, mt-genomes are characterized by varying numbers of both linear and circular chromosomes, extra genes (e.g. atp9, polB, tatC), large variation in the number of encoded mitochondrial transfer RNAs (tRNAs) (0-25), at least seven different genetic codes, presence/absence of introns, tRNA and mRNA editing, fragmented ribosomal RNA genes, translational frameshifting, highly variable substitution rates, and a large range of genome sizes. This newly discovered diversity allows a better understanding of the evolutionary plasticity and conservation of animal mtDNA and provides insights into the molecular and evolutionary mechanisms shaping mitochondrial genomes. PMID- 27557829 TI - Usefulness of Surgical Apgar Score on Predicting Survival After Surgery for Gastric Cancer. AB - BACKGROUND: Complete surgical resection is essential for a cure for most gastric cancer. Recently it was reported that surgical Apgar score (SAS) can predict postoperative complication and that postoperative complication is associated with poor long-term survival. The aim of this study is to assess whether SAS can predict overall survival (OS) after surgery for gastric cancer. METHODS: We retrospectively compared clinicopathological characteristics and survival between high and low SAS score groups in patients who underwent gastrectomy for gastric cancer. RESULTS: Low-scored SAS group (group L) was significantly more common among ASA-PS 2, open approach, total gastrectomy, D2 lymph node dissection, postoperative complication grade 2-4, deep tumor invasion, lymph node metastases, and advanced pathological TNM stage than high-scored SAS group (group H). The 5 year OS of group H and group L were 81.6 and 55.9 %, respectively (p < .001); OS of group L tended to be poorer than that of group H in stage III patients (p = .060) and in stage IV patients (p < .001). In multivariate analysis, pathological stage and SAS were identified as independent predictors for OS. CONCLUSIONS: SAS is useful for predicting survival after surgery for gastric cancer. PMID- 27557830 TI - Second-Line Treatment of Non-Small Cell Lung Cancer: New Developments for Tumours Not Harbouring Targetable Oncogenic Driver Mutations. AB - Platinum-based doublet chemotherapy with or without bevacizumab is the standard of care for the initial management of advanced and metastatic non-small cell lung cancer (NSCLC) without a targetable molecular abnormality. However, the majority of patients with NSCLC will ultimately develop resistance to initial platinum based chemotherapy, and many remain candidates for subsequent lines of therapy. Randomised trials over the past 10-15 years have established pemetrexed (non squamous histology), docetaxel, erlotinib and gefitinib as approved second-line agents in NSCLC without targetable driver mutations or rearrangements. Trials comparing these agents with other chemotherapy, evaluating the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to chemotherapy or the addition of another targeted agent to erlotinib or gefitinib have all failed to demonstrate an improvement in overall survival for patients with NSCLC. In contrast, recent data comparing therapy with novel monoclonal antibodies against programmed cell death 1 (PD-1) or PD ligand (PD-L1) pathway versus standard chemotherapy following platinum failure have demonstrated significant improvements in overall survival. Therapy with nivolumab or pembrolizumab would now be considered standard second-line therapy in patients without contraindication to immune checkpoint inhibitors. Atezolizumab also appears promising in this setting. PMID- 27557831 TI - CORR Insights (r): Is Hepatitis C Infection Associated With a Higher Risk of Complications After Total Shoulder Arthroplasty? PMID- 27557832 TI - Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: a qualitative analysis. AB - PURPOSE: To better understand how physicians communicate with breast cancer patients about adjuvant endocrine therapy (AET), we explored, from the breast cancer patient's perspective, dimensions of the patient-provider communication among women who were on active AET treatment. METHODS: Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes from interview data. RESULTS: We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self management and monitoring potential side effects, and (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient's health literacy regarding the benefits and knowledge of AET. Physicians empowered patients to make decisions about their care. Patients expressed trust and confidence in their physician which helped them seek care when needed. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side effects. CONCLUSIONS: The results from our study suggest that women's interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who can communicate information about AET treatment benefits, purpose, and expectations in a way that patients can understand is a critical aspect of care that needs to be further studied. PMID- 27557833 TI - Rolapitant improves quality of life of patients receiving highly or moderately emetogenic chemotherapy. AB - PURPOSE: Addition of rolapitant to standard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting (CINV) in phase 3 trials of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Here, we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis (FLIE). METHODS: In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18-126]). We performed a prespecified analysis of the MEC/anthracycline cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies. RESULTS: In the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p < 0.001), nausea score (55.3 vs 53.5, p < 0.05), and vomiting score (59.2 vs 55.8, p < 0.001) versus control; similar results were observed in the MEC/AC study for FLIE total score (112.7 vs 108.6, p < 0.001), nausea score (54.1 vs 52.3, p < 0.05), and vomiting score (58.6 vs 56.3, p < 0.001). A higher proportion of patients reported no impact on daily life with rolapitant than with control in the MEC/AC study (73.2 vs 67.4, p = 0.027). CONCLUSIONS: Compared with control, rolapitant improved quality of life in patients receiving HEC or MEC. PMID- 27557834 TI - Supporting self-management of pain by patients with advanced cancer: views of palliative care professionals. AB - PURPOSE: The aim of the study is to ascertain the views of specialist palliative care professionals on patient self-management of cancer pain in order to inform the development of a new educational intervention to support self-management. METHODS: This is a qualitative research study using focus group interviews. RESULTS: Participants viewed self-management of cancer pain as desirable and achievable but also as something that could be problematic. Challenges to self management were perceived in patient attitudes and behaviours, professionals' own beliefs and actions and the wider social system. Practitioners showed awareness of potential tension between their espoused views (the desirability that patients manage pain autonomously) and their tacit views (the undesirability of patients managing pain in ways which conflict with professionals' knowledge and identity). CONCLUSIONS: Practitioners espoused patient-centred professional practice which inclined them towards supporting self-management. They showed awareness of factors which might inhibit them from effectively incorporating education and support for self-management into routine practice. PMID- 27557835 TI - "My body was my temple": a narrative revealing body image experiences following treatment of a spinal cord injury. AB - PURPOSE: This narrative explores the lived experience of a young woman, Rebecca, and her transitioned body image after sustaining and being treated for a spinal cord injury. METHOD: Data were collected from a single semi-structured in-depth interview. RESULTS: Rebecca disclosed her transitioned body image experiences after sustaining a spinal cord injury and being treated by medical staff immediately following her injury. Before her injury, she described a holistic body experience and named this experience her "temple". During intensive care in the hospital, she explained her body was treated as an object. The disconnected treatment of her body led to a loss of the private self, as she described her sacred body being stripped away - her "temple" lost and in ruins. CONCLUSIONS: Body image may be an overlooked component of health following a spinal cord injury. This narrative emphasizes the importance of unveiling body image experiences after the treatment of a spinal cord injury to medical professionals. Lessons of the importance of considering the transitioned body experiences after a spinal cord injury may help prevent body-related depression and other subsequent health impacts. Recommendations for best practice are provided. Implications for Rehabilitation Spinal Cord Injury * A spinal cord injury may drastically change a person's body image, thereby significantly impacting psychological health * More effective screening for body image within the medical/rehabilitation context is needed to help practitioners recognize distress * Practitioners should be prepared to refer clients to distress hotlines they may need once released from treatment. PMID- 27557836 TI - Probiotic Potential of Autochthonous Bacteria Isolated from the Gastrointestinal Tract of Four Freshwater Teleosts. AB - In this study, a total of 121 bacterial strains were isolated from the gastrointestinal tract of four teleostean species, namely striped snakehead (Channa striatus), striped dwarf catfish (Mystus vittatus), orangefin labeo (Labeo calbasu) and mrigal carp (Cirrhinus mrigala), among which 8 isolates showed promising antibacterial activity against four potential fish pathogens, Aeromonas hydrophila, Aeromonas salmonicida, Aeromonas sobria and Pseudomonas fluorescens and were non-hemolytic. The isolates were further screened in response to fish bile tolerance and extracellular digestive enzyme activity. Two bacterial strains MVF1 and MVH7 showed highest tolerance and extracellular enzymes activities, and selected for further studies. Antagonistic activity of these two isolates was further confirmed by in vitro growth inhibition assay against four selected fish pathogens in liquid medium. Finally, these two bacterial strains MVF1 and MVH7 were selected as potential probiotic candidates and thus identification by partial 16S rRNA gene sequence analysis. The bacterial isolates MVF1 and MVH7 were identified as two strains of Bacillus sp. PMID- 27557837 TI - Effects of Colistin and Bacteriocins Combinations on the In Vitro Growth of Escherichia coli Strains from Swine Origin. AB - Escherichia coli strains from swine origin, either susceptible or resistant to colistin, were grown under planktonic and biofilm cultures. After which, they were treated with antibacterial agents including nisin and enterocin DD14 bacteriocins, colistin and their combinations. Importantly, the combination of colistin, enterocin DD14 and nisin eradicated the planktonic and biofilm cultures of E. coli CIP54127 and the E. coli strains with colistin-resistance phenotype such as E. coli 184 (mcr-1 +) and E. coli 289 (mcr-1 -), suggesting therefore that bacteriocins from lactic acid bacteria could be used as agents with antibiotic augmentation capability. PMID- 27557838 TI - One-step Solution Processing of Ag, Au and Pd@MXene Hybrids for SERS. AB - We report on one-step hybridization of silver, gold and palladium nanoparticles from solution onto exfoliated two-dimensional (2D) Ti3C2 titanium carbide (MXene) nanosheets. The produced hybrid materials can be used as substrates for surface enhanced Raman spectroscopy (SERS). An approximate analytical approach is also developed for the calculation of the surface plasmon resonance (SPR) frequency of nanoparticles immersed in a medium, near the interface of two dielectric media with different dielectric constants. We obtained a good match with the experimental data for SPR wavelengths, 440 nm and 558 nm, respectively for silver and gold nanoparticles. In the case of palladium, our calculated SPR wavelength for the planar geometry was 160 nm, demonstrating that non-spherical palladium nanoparticles coupled with 2D MXene yield a broad, significanlty red-shifted SPR band with a peak at 230 nm. We propose a possible mechanism of the plasmonic hybridization of nanoparticles with MXene. The as-prepared noble metal nanoparticles on MXene show a highly sensitive SERS detection of methylene blue (MB) with calculated enhancement factors on the order of 10(5). These findings open a pathway for extending visible-range SERS applications of novel 2D hybrid materials in sensors, catalysis, and biomedical applications. PMID- 27557839 TI - How to use a controlled fast to investigate hypoglycaemia. AB - Controlled fasts can play a valuable role in the diagnosis and management of hypoglycaemia in paediatric clinical practice, but are no substitute for the collecting of appropriate critical samples at the time of hypoglycaemia for metabolic and endocrine studies. Fatty acid oxidation defects, hyperinsulinism and adrenal insufficiency should always be excluded prior to organising controlled fasts. Controlled fasts are safe if conducted in an experienced setting with strict protocols in place. Failure to adhere to protocol can defeat the purpose of the study and can potentially be dangerous. Proper planning in conjunction with the laboratory and close supervision by staff experienced in controlled fasts is crucial to ensure the best quality information is yielded from these procedures. PMID- 27557840 TI - Claims for disease-modifying therapy by Alberta non-insured health benefits clients. AB - BACKGROUND: Uncontrolled disease activity in inflammatory diseases of the joints, skin and bowel leads to morbidity and disability. Disease-modifying therapies are widely used to suppress this disease activity, but cost-coverage is variable. For Treaty First Nations and Inuit people in Canada without alternative private or public health insurance, cost-coverage for disease-modifying therapy is provided through Non-Insured Health Benefits (NIHB). Our objective was to describe the prevalence and patterns of treatment with disease-modifying therapy for the NIHB claimant population, and also examine adjuvant therapy (analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids) use. METHODS: Cases (n = 2512) were defined by >=1 claim for a disease-modifying anti-rheumatic drug (DMARD) or biologic between 1999 and 2012 in the NIHB pharmacy claim database. The proportion of the population with claims for individual agents and drug classes annually was calculated to estimate annual incidence and prevalence rates for use of disease-modifying therapy, and the prevalence of use of individual DMARDs, biologics and adjuvants. Differences in the proportion accessing adjuvant therapies and median doses in the 6 months following initiation of disease modifying therapies was estimated. RESULTS: The incidence rate of treatment was calculated at an average of 127.5 cases per 100,000 population between 2001 and 2012, and the cumulative prevalence, accounting for patients lost to the database, increased and then stabilized at 1.3 % in the last three years of the study. Annual dispensation of methotrexate, combination DMARD therapy and biologic therapy approached 35 %, 19 %, and 10 % of the cohort respectively. A declining prevalence of claims for acetaminophen (28 % to 15 %) and anti inflammatories (73 % to 63 %) occurred from 2000 to 2012, however corticosteroid (32 %) and opioid (65 %) dispensation remained stable. The proportion of patients with claims for NSAIDs (69.9 % to 61.1 %, p = 0.002), oral corticosteroids (45.4 % to 33.6 %, p < 0.001) and parenteral corticosteroids (16.2 % to 8.3 %, p = 0.002) decreased in the 6 months following biologic initiation. CONCLUSIONS: The proportion of NIHB clients with active claims for disease-modifying therapy is lower than expected based on existing epidemiologic knowledge of the prevalence of inflammatory conditions in the First Nations and Inuit populations. These findings should be further explored in order to optimize treatment outcomes for NIHB claimants with inflammatory disease. PMID- 27557841 TI - Endocrine disruptor phthalates in bottled water: daily exposure and health risk assessment in pregnant and lactating women. AB - Over the last decade, the consumption of water bottled in polyethylene terephthalate (PET) has considerably increased, raising concerns over water quality and packaged materials. This study aims to investigate the levels of the anti-androgenic phthalates including bis-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP), in bottled water and its corresponding health risks in pregnant and lactating women. The phthalate levels were measured in six different brands of bottled water exposed to temperatures ranging between -18 and 40 degrees C and sunlight for 45 days. The phthalate was quantified using the gas chromatography-mass spectrometry (GC-MS). In addition, the non-carcinogenic effects were assessed using hazard quotient (HQ) approach, and cumulative health risk assessment was performed on the basis of hazard index (HI) calculation. In order to assess the carcinogenic risk due to the possible carcinogen DEHP (group 2B), the excess lifetime cancer risk (ELCR) was used. DEHP and DBP contaminants were detected at different storage conditions in all of the bottled water samples during the storage time. BBP was only detected at high temperature (>=25 degrees C) and outdoor conditions. The maximum concentrations of all phthalates were observed when water samples were kept at 40 degrees C. In contrast, storage at freezing conditions had no significant effect on the concentration level of all phthalates. The estimated intake by women was between 0.0021 MUg/kg/day for BBP and 0.07 MUg/kg/day for DEHP. The highest HQ for phthalate intake via bottled water consumption was much lower than 1 (HQ < 0.004), which implies that adverse effects are very unlikely to occur. The execution of a cumulative risk assessment for combined phthalate exposure demonstrated that the HIs for anti-androgenic effect were lower than 1 in all of the conditions. Furthermore, ELCR for DEHP based on the highest detected level was found to be less than 10(-6), which is considered acceptable. Our results prove that the levels of phthalates in bottled water are not a health concern for pregnant and lactating women. Consequently, PET-bottled water is not a major contributor to phthalate intake for most individuals. PMID- 27557842 TI - Rhizobium hidalgonense sp. nov., a nodule endophytic bacterium of Phaseolus vulgaris in acid soil. AB - One Gram-negative, aerobic, motile, rod-shaped bacterium, designated as FH14T, was isolated from nodules of Phaseolus vulgaris grown in Hidalgo State of Mexico. Results based upon 16S rRNA gene (>=99.8 % similarities to known species), concatenated sequence (recA, atpD and glnII) analysis of three housekeeping genes (<=93.4 % similarities to known species) and average nucleotide identity (ANI) values of genome sequence (ranged from 87.6 to 90.0 % to related species) indicated the distinct position of strain FH14T within the genus Rhizobium. In analyses of symbiotic genes, only nitrogen fixation gene nifH was amplified that had nucleotide sequence identical to those of the bean-nodulating strains in R. phaseoli and R. vallis, while nodulation gene nodC gene was not amplified. The failure of nodulation to its original host P. vulgaris and other legumes evidenced the loss of its nodulation capability. Strain FH14T contained summed feature 8 (C18:1 omega6c/C18:1 omega7c, 59.96 %), C16:0 (10.6 %) and summed feature 2 (C12:0 aldehyde/unknown 10.928, 10.24 %) as the major components of cellular fatty acids. Failure to utilize alaninamide, and utilizing L-alanine, L asparagine and gamma-amino butyric acid as carbon source, distinguished the strain FH14T from the type strains for the related species. The genome size and DNA G+C content of FH14T were 6.94 Mbp and 60.8 mol %, respectively. Based on those results, a novel specie in Rhizobium, named Rhizobium hidalgonense sp. nov., was proposed, with FH14T (=HAMBI 3636T = LMG 29288T) as the type strain. PMID- 27557843 TI - Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection. AB - BACKGROUND: Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow, known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study, we set out to investigate if increased cerebral levels of IL-1 have a negative effect on the neurovascular coupling in the cortex in response to sensory stimulation. METHODS: We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intra-striatal injection of interleukin-1beta or vehicle. First, we used two-dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals, immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of interleukin-1beta (IL-1beta). Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a 'Clark-style' electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi unit activity (MUA) together with local field potentials (LFPs), respectively. RESULTS: 2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1beta injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1beta injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-band activity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post-IL-1beta injection, whereas IL-1beta had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1beta-injected group. CONCLUSIONS: We conclude that intra-striatal IL 1beta decouples cortical neuronal activity from its haemodynamic response. This finding may have implications for neurological conditions where IL-1beta plays a part, especially those involving reductions in cerebral blood flow (such as stroke). PMID- 27557844 TI - Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT. AB - PURPOSE: Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11C choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand 68Ga-PSMA-11 with 11C-choline in patients with primary and recurrent prostate cancer. METHODS: 123 patients underwent a whole-body PET/CT examination using 68Ga-PSMA-11 and 11C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. RESULTS: In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using 68Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11C-choline PET. Also 68Ga PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by 68Ga-PSMA 11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per 11C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by 68Ga PSMA-11 PET. CONCLUSION: Thus, PET using 68Ga-PSMA-11 showed a higher detection rate than 11C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers. PMID- 27557845 TI - Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging. AB - PURPOSE: To dynamically detect and characterize 18F-fluorodeoxyglucose (FDG) dose infiltrations and evaluate their effects on positron emission tomography (PET) standardized uptake values (SUV) at the injection site and in control tissue. METHODS: Investigational gamma scintillation sensors were topically applied to patients with locally advanced breast cancer scheduled to undergo limited whole body FDG-PET as part of an ongoing clinical study. Relative to the affected breast, sensors were placed on the contralateral injection arm and ipsilateral control arm during the resting uptake phase prior to each patient's PET scan. Time-activity curves (TACs) from the sensors were integrated at varying intervals (0-10, 0-20, 0-30, 0-40, and 30-40 min) post-FDG and the resulting areas under the curve (AUCs) were compared to SUVs obtained from PET. RESULTS: In cases of infiltration, observed in three sensor recordings (30 %), the injection arm TAC shape varied depending on the extent and severity of infiltration. In two of these cases, TAC characteristics suggested the infiltration was partially resolving prior to image acquisition, although it was still apparent on subsequent PET. Areas under the TAC 0-10 and 0-20 min post-FDG were significantly different in infiltrated versus non-infiltrated cases (Mann-Whitney, p < 0.05). When normalized to control, all TAC integration intervals from the injection arm were significantly correlated with SUVpeak and SUVmax measured over the infiltration site (Spearman rho >= 0.77, p < 0.05). Receiver operating characteristic (ROC) analyses, testing the ability of the first 10 min of post FDG sensor data to predict infiltration visibility on the ensuing PET, yielded an area under the ROC curve of 0.92. CONCLUSIONS: Topical sensors applied near the injection site provide dynamic information from the time of FDG administration through the uptake period and may be useful in detecting infiltrations regardless of PET image field of view. This dynamic information may also complement the static PET image to better characterize the true extent of infiltrations. PMID- 27557846 TI - Acknowledging gray areas: 2015 vs. 2009 American Thyroid Association differentiated thyroid cancer guidelines on ablating putatively low-intermediate risk patients. AB - PURPOSE: Typically formulated by investigators from "world centres of excellence," differentiated thyroid carcinoma (DTC) management guidelines may have more limited applicability in settings of less expert care and fewer resources. Arguably the world's leading DTC guidelines are those of the American Thyroid Association, revised in 2009 ("ATA 2009") and 2015 ("ATA 2015"). To further explore the issue of "real-world applicability" of DTC guidelines, we retrospectively compared indications for ablation using ATA 2015 versus ATA 2009 in a two-centre cohort of ablated T1-2, M0 DTC patients (N = 336). Based on TNM status and histology, these patients were low-intermediate risk, but many ultimately had other characteristics suggesting elevated or uncertain risk. METHODS: Working by consensus, two experienced nuclear medicine physicians considered patient and treatment characteristics to classify each case as having "no indication," a "possible indication," or a "clear indication" for ablation according to ATA 2009 or ATA 2015. The physicians also identified reasons for classification changes between ATA 2015 versus ATA 2009. Classification was unblinded, but the physicians had cared for only 138/336 patients, and the charts encompassed September 2010-October 2013, several years before the classification was performed. RESULTS: One hundred of 336 patients (29.8 %) changed classification regarding indication for ablation using ATA 2015 versus ATA 2009. Most reclassified patients (70/100) moved from "no indication" or "clear indication" to "possible indication." Reflecting this phenomenon, "possible indication" became the largest category according to the ATA 2015 classification (141/336, 42.0 %, versus 96/336, 28.6 %, according to ATA 2009). Many reclassifications were attributable to multiple clinicopathological characteristics, most commonly, stimulated thyroglobulin or anti-thyroglobulin antibody levels, multifocality, bilateral involvement, or capsular/nodal invasion. CONCLUSIONS: Regarding indications for ablation, ATA 2015 appears to better "acknowledge grey areas," i.e., patients with ambiguous or unavailable data requiring individualised, nuanced decision-making, than does ATA 2009. PMID- 27557847 TI - PET/CT imaging for evaluating response to therapy in castration-resistant prostate cancer. PMID- 27557848 TI - Solvent-Triggered Cis/Trans Isomerism in Cobalt Dioxolene Chemistry: Distinguishing Effects of Packing on Valence Tautomerism. AB - In this article, the synthesis and X-ray crystal structures of two cis/trans isomers of valence tautomeric (VT) cobalt dioxolene compounds are reported. The cis isomer (1) was isolated from the polar protic methanol solvent as a kinetic product, whereas the less polar nonprotic solvent acetone yielded the trans isomer (2). It should be noted that, although some coordination polymers involving cobalt bis(dioxolene) with the cis disposition are known for bridging ancillary ligands, such an arrangement is unprecedented for mononuclear compounds. A careful study of intermocular interactions revealed that the methanol solvent does not have much influence on the crystal growth in 1, whereas acetone forms strong halogen-bonding interactions that are crucial in the solid state architecture of 2. This behavior can likely be used in crystal engineering to design new organic-inorganic hybrid materials. The energy difference between the two isomers was examined using DFT calculations, confirming that the trans form is in the thermodynamic state whereas the cis isomer is a kinetic product that can be converted into the trans isomer with time. Finally, both isomers exhibit solvent loss at elevated temperatures that is accompanied by a change in magnetic properties, associated with an irreversible valence tautomerism. Our results highlight the crucial role of the solvents for the isolation of cis/trans isomers in cobalt dioxolene chemistry, as well as the distinguishing effects of intermolecular forces and the solid-state packing on VT behavior. PMID- 27557850 TI - Is the ORBIT Bleeding Risk Score Superior to the HAS-BLED Score in Anticoagulated Atrial Fibrillation Patients? AB - BACKGROUND: Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in "real world" anticoagulated AF patients. METHODS AND RESULTS: We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66-0.88) and 0.82 (95% CI 0.77-0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56-0.71) and 0.70 (95% CI 0.62-0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as "low risk". CONCLUSIONS: Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a "real world" oral anticoagulated AF population. (Circ J 2016; 80: 2102-2108). PMID- 27557851 TI - Focal Vasa Vasorum Formation in Patients With Focal Coronary Vasospasm - An Optical Frequency Domain Imaging Study. PMID- 27557849 TI - Assessment of pets (cats and dogs) in homes using electrostatic dust collectors and QPCR: new tools to evaluate exposure and risk of allergies. AB - Contradictory results are found in the literature concerning fungi, bacteria, and pet exposure and the risk of developing asthma. All these allergens have been thoroughly studied separately in cohort studies, and a variety of sampling and analytical methods are used. It is already possible to characterize fungi, mites, and bacteria by QPCR. The aim of our study is to evaluate QPCR systems to quantify the presence of cats and dogs in homes. Twenty-four houses were sampled with an Electrostatic Dust Collector which was analyzed by QPCR. Questionnaires on the presence of pets in homes were completed. The results from QPCR were correlated for real presence of cats and dogs, and highlighted indirect exposure. This study provides a useful screening tool that will be used in future large cohort studies, such as the ELFE cohort study. PMID- 27557852 TI - Perinatal outcome of monochorionic diamniotic twin pregnancies complicated with isolated amniotic fluid volume abnormality of one twin less than 26 weeks of gestation. AB - AIM: To evaluate the incidence of twin-twin transfusion syndrome (TTTS) and the perinatal outcome at 28 days of age in monochorionic diamniotic (MCDA) pregnancies complicated with isolated polyhydramnios (I-Poly) and isolated oligohydramnios (I-Oligo) diagnosed < 26 weeks of gestation. METHODS: This was a retrospective study of women with MCDA pregnancies diagnosed with I-Poly or I Oligo before 26 weeks of gestation over a period of six years. The incidence of subsequent TTTS and neonatal outcome in terms of intact survival (IS) at 28 days of age were evaluated. Intact survival was defined as being alive without any neurological complications at 28 days of age. RESULTS: There were 30 cases of I Poly and 53 of I-Oligo that were eligible as per the inclusion criteria. Subsequent TTTS were complicated in six (20.0%) of the I-Poly and 26 (49.0%) of the I-Oligo cases. Among subjects with I-Poly, 17 had spontaneously normalized amniotic fluid volume. Prolonged oligohydramnios until intrauterine death, delivery or the onset of emerging TTTS was noted in 16 cases of I-Oligo. Both the twins exhibited IS in 26 (86.7%) cases of I-Poly and 31 (58.4%) cases of I-Oligo. CONCLUSION: One-fifth of I-Poly and half of I-Oligo MCDA twins at < 26 weeks of gestation potentially develop TTTS. I-Oligo in particular should be regarded as a high-risk condition as neonatal IS is less than 60%. PMID- 27557854 TI - C-Dot Generated Bioactive Organosilica Nanospheres in Theranostics: Multicolor Luminescent and Photothermal Properties Combined with Drug Delivery Capacity. AB - Biocompatible nanomaterials that allow for labeling cells and tissues with the capacity to load and deliver drug molecules hold great promise for the therapeutic-diagnostic purposes in tissue repair and disease cure. Here a novel nanoplatform, called C-dot bioactive organosilica nanosphere (C-BON), is introduced to have excellent theranostic potential, such as controlled drug delivery, visible-light imaging, and NIR photothermal activity. C-dots with a few nanometers were in situ generated in the Ca-containing organosilica mesoporous nanospheres through the sol-gel and thermal-treatment processes. The C-BON exhibited multicolor luminescence over a wide visible-light range with strong emissions and high photostability over time and against acidity and the possible in vivo optical imaging capacity when injected in rat subcutaneous tissues. Moreover, the C-BON showed a photothermal heating effect upon the irradiation of near-infrared. The C-BON, thanks to the high mesoporosity and existence of Ca(2+) ions, demonstrated excellent loading capacity of anticancer drug doxorubicin (as high as 90% of carrier weight) and long-term (over a couple of weeks) and pH/NIR dependent release ability. The C-BON preserved the compositional merit of Ca-Si glass, having excellent bioactivity and cell compatibility in vitro. Taken all, the multifunctional properties of C-BON-multicolor luminescence, photothermal activity, and high drug loading and controlled release-together with its excellent bioactivity and cell compatibility potentiate the future applications in theranostics (chemotherapy and photothermal therapy with optical imaging). PMID- 27557853 TI - A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice. AB - OBJECTIVE: Romiplostim has maintained long-term platelet counts in patients with immune thrombocytopenia (ITP) for up to 5 yr in clinical studies. This prospective observational study aimed to describe romiplostim utilisation and outcomes in European clinical practice. METHODS: Adults with primary ITP who received romiplostim in routine care were eligible. RESULTS: Three-hundred and forty patients were eligible for analysis, of whom 299 (88%) completed the 2-yr observation period. The median age was 62 yr, with 43% of patients aged >=65 yr, and two-thirds of patients initiated romiplostim before splenectomy. The median average weekly dose of romiplostim was 2.8 MUg/kg. The median baseline platelet count was 20 * 109 /L, which increased after 2 wk of romiplostim treatment and remained >50 * 109 /L thereafter. After romiplostim initiation, there was a decrease in rates of grade >=3 bleeding events (from 12 to 2 per 100 patient years) and ITP-related hospitalisations (from 87 to 33 per 100 patient-years). The rate of thrombotic events was 2 per 100 patient-years, and bone marrow fibrosis occurred in two patients. CONCLUSIONS: Romiplostim dosing, effectiveness and safety in an unselected real-world ITP population seemed comparable with that observed in clinical studies. PMID- 27557855 TI - Inhibition of Bacillus anthracis metallo-beta-lactamase by compounds with hydroxamic acid functionality. AB - Metallo-beta-lactamases (MBLs) that catalyze hydrolysis of beta-lactam antibiotics are an emerging threat due to their rapid spread. A strain of the bacterium Bacillus anthracis has its ability to produce and secrete a MBL, referred to Bla2. To address this challenge, novel hydroxamic acid-containing compounds such as 3-(heptyloxy)-N-hydroxybenzamide (compound 4) and N-hydroxy-3 ((6-(hydroxyamino)-6-oxohexyl)oxy)benzamide (compound 7) were synthesized. Kinetic analysis of microbial inhibition indicated that the both sides of hydroxamic acids containing compound 7 revealed a reversible, competitive inhibition with a Ki value of 0.18 +/- 0.06 MUM. The result has reflected that the both sides of dihydroxamic acids in a molecule play a crucial role in the binding affinity rather than monohydroxamic containing compound 4 which was unable to inhibit Bla2. In addition, in silico analysis suggested that compound 7 was coordinated with a zinc ion in the active site of enzyme. These observations suggest that the dihydroxamic acid-containing compound may be a promising drug candidate, and a further implication for designing new inhibitors of Bla2. PMID- 27557856 TI - Exploration of pathological prediction of chronic kidney diseases by a novel theory of bi-directional probability. AB - In the clinic, the pathological types of chronic kidney diseases (CKD) are considered references for choosing treatment protocols. From a statistical viewpoint, a non-invasive method to predict pathological types of CKD is a focus of our work. In the current study, following a frequency analysis of the clinical indices of 588 CKD patients in the department of nephrology, a third-grade class A hospital, a novel theory is proposed: "bi-directional cumulative probability dichotomy". Further, two models for the prediction and differential diagnosis of CKD pathological type are established. The former indicates an occurrence probability of the pathological types, and the latter indicates an occurrence of CKD pathological type according to logistic binary regression. To verify the models, data were collected from 135 patients, and the results showed that the highest accuracy rate on membranous nephropathy (MN-100%), followed by IgA nephropathy (IgAN-83.33%) and mild lesion type (MLN-73.53%), whereas lower prediction accuracy was observed for mesangial proliferative glomerulonephritis (0%) and focal segmental sclerosis type (21.74%). The models of bi-directional probability prediction and differential diagnosis indicate a good prediction value in MN, IgAN and MLN and may be considered alternative methods for the pathological discrimination of CKD patients who are unable to undergo renal biopsy. PMID- 27557857 TI - High HIV prevalence and the internet as a source of HIV-related service information at a community-based organization in Peru: a cross-sectional study of men who have sex with men. AB - BACKGROUND: The HIV prevalence among men who have sex with men (MSM) in Peru (12.4 %) is 30 times higher than in the general adult population (0.4 %). It is critical for community-based organizations to understand how to provide HIV services to MSM while maximizing limited resources. This study describes the HIV prevalence and risk profiles of MSM seeking HIV services at a community-based organization in Lima, Peru. It then compares HIV prevalence between those who found out about the HIV services through different sources. METHODS: A cross sectional study of MSM seeking HIV services at Epicentro Salud in Lima, Peru for the first time between April 2012 and October 2013. We compared HIV prevalence among MSM who found out about Epicentro via online sources of information (N = 419), those using in-person sources (friends, partners) (N = 907), and sex workers (N = 140) using multivariable logistic regression models. RESULTS: HIV prevalence was 18.3 % overall: 23.2 % among MSM using online sources, 19.3 % among sex workers, and 15.9 % among MSM using in-person sources. However, when compared to the in-person group, sexual risk behaviors were not statistically higher among MSM using online sources. For the sex worker group, some behaviors were more common, while others were less. After adjusting for confounders, the odds of having HIV was higher for the online group (Odds Ratio = 1.61; 95 % Confidence Interval: 1.19-2.18), but not for the sex worker group (OR = 1.12; 95 % CI: 0.68-1.86), compared to the in-person group. CONCLUSION: Internet-based promotion appears to successfully reach MSM at high risk of HIV in Peru. Outreach via this medium can facilitate HIV diagnosis, which is the critical first step in getting infected individuals into HIV care. For community-based organizations working in resource-limited settings, this may be an effective strategy for engaging a subset of high-risk persons in HIV care. PMID- 27557859 TI - Implementing change. PMID- 27557860 TI - Evaluation of the psychometric properties of the London Measure of Unplanned Pregnancy in Brazilian Portuguese. AB - BACKGROUND: Estimates of unplanned pregnancy worldwide are of concern, especially in low and middle-income countries, including Brazil. Although the contraceptive prevalence rate is high in Brazil, almost half of all pregnancies are reported as unintended. The only source of nationally representative data about pregnancy intention is the Demographic and Health Survey, as with many other countries. In more recent years, however, it has been realized that concept of unintended pregnancy is potentially more complex and requires more sophisticated measurement strategies, such as the London Measure of Unplanned Pregnancy (LMUP). The LMUP has been translated and validated in other languages, but not Portuguese yet. In this study, we evaluate the psychometric properties of the LMUP in the Portuguese language, Brazilian version. METHODS: A Brazilian Portuguese version of the LMUP was produced via translation and back-translation. After piloting, the mode of administration was changed from self-completion to interviewer-administration. The measure was field tested with pregnant, postpartum, and postabortion women recruited at maternity and primary health care services in Sao Paulo city. Reliability (internal consistency) was assessed using Cronbach's alpha and item total correlations. Construct validity was assessed using principal components analysis and hypothesis testing. Scaling was assessed with Mokken analysis. RESULTS: 759 women aged 15-44 completed the Brazilian Portuguese LMUP. There were no missing data. The measure was acceptable and well targeted. Reliability testing demonstrated good internal consistency (alpha = 0.81, all item-rest correlations >0.2). Validity testing confirmed that the measure was unidimensional and that all hypotheses were met: there were lower LMUP median scores among women in the extreme age groups (p < 0.001), among non-married women (p < 0.001) and those with lower educational attainment (p < 0.001). The Loevinger H coefficient was 0.60, indicating a strong scale. CONCLUSION: The Brazilian Portuguese LMUP is a valid and reliable measure of pregnancy planning/intention that is now available for use in Brazil. It represents a useful addition to the public health research and surveillance toolkit in Brazil. PMID- 27557861 TI - Baseline and Change in Uric Acid Concentration Over Time Are Associated With Incident Hypertension in Large Korean Cohort. AB - BACKGROUND: It is uncertain whether high-baseline uric acid (UA) or change in UA concentration over time is related to development of incident hypertension. To investigate relationships between: (i) baseline serum UA concentration and (ii) change in UA concentration and incident hypertension. METHODS: About 96,606 Korean individuals (with follow-up UA data available for 56,085 people) participating in a health check program was undertaken. Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident hypertension according to UA quartiles regarding the lowest UA quartile as the reference, and also according to change in UA concentration comparing individuals with an increase in UA to those with a decrease in UA concentration over time. RESULTS: Total follow up time was 8 years (median follow up 3.3 years; interquartile range, 1.9-5.1). About 10,405 cases of incident hypertension occurred. In the fully adjusted regression models, the HRs (95% CI) for incident hypertension comparing the highest vs. the lowest quartiles of UA were 1.29 (1.19-1.38) in men and 1.24 (1.09-1.42) in women, with statistically significant P for trend for both gender. Additionally, stable or increasing UA concentration over time was associated with increased risk of incident hypertension, particularly in participants with baseline UA concentration >=median (aHRs 1.14; 95% CI (1.03-1.26) and 1.18; 95% CI (0.98-1.40) in men and women, respectively). CONCLUSIONS: High initial UA concentration and increases in UA concentration over time should be considered independent risk factors for hypertension. PMID- 27557862 TI - The Use of Telmisartan and the Incidence of Cancer. AB - BACKGROUND: A meta-analysis reported an 8% increased risk of cancer with the use of angiotensin receptor blockers (ARBs), but subsequent meta-analyses and observational studies did not confirm this risk. However, telmisartan comprised 85% of the data in the original meta-analysis. Thus, the objective of this study was to determine whether the use of telmisartan, compared with other ARBs, is associated with an increased risk of cancer. METHODS: We used the United Kingdom Clinical Practice Research Datalink to assemble a cohort of all patients newly treated with ARBs between 2000 and 2008, and followed until December 2010. Time dependent cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer associated with telmisartan, compared with other ARBs, adjusted for potential confounders. Secondary analyses assessed the risk with each of the 4 most common cancers (lung, breast, prostate, colorectal). RESULTS: The cohort consisted of 62,109 new ARB users, which included 3,438 telmisartan and 58,671 other ARB users. Compared with other ARBs, telmisartan use was not associated with an increased risk of cancer overall (16.3 vs. 15.0 per 1,000 person-years, respectively; adjusted HR: 0.93, 95% CI: 0.81 1.06) or by cancer site (lung, HR: 0.91, 95% CI: 0.55-1.51; breast, HR: 1.28, 95% CI: 0.90-1.82; prostate, HR: 0.79, 95% CI: 0.53-1.18; colorectal, HR: 1.41, 95% CI 0.95-2.10). CONCLUSIONS: Compared with other ARBs, telmisartan is not associated with an increased risk of cancer. This study provides reassurance as to the short-term safety of telmisartan. PMID- 27557863 TI - The Australian experience following plain packaging: the impact on tobacco branding. AB - AIMS: Brands are critical to tobacco marketing. Industry stakeholders predicted that plain packaging, by removing key tangible branding dimensions, would restrict new products and brand differentiation. However, manufacturers respond innovatively to limit regulatory impact. This study investigates brand strategy following plain packaging's introduction to Australia. METHODS: Brand portfolios were determined using 2006-15 tobacco ingredient reports. These detail the brand and variant names sold and are provided annually as part of a voluntary agreement between the Australian Government and leading manufacturers. Post-plain packaging brand ranges were verified using retail price lists and a supermarket retail audit using a method used previously to verify a period of pre-plain packaging data. RESULTS: The verification process identified some data inaccuracies from one manufacturer which resulted in the issuing of corrected data. After plain packaging the leading manufacturers continued with extensive brand ranges differentiated by price. All launched new products. While total brand numbers fell from 29 to 24, the mean number of variants for the leading 12 brands grew from 8.9 to 9.7. Substantial variant name modifications occurred with 50 new or modified names in 2012-13. Among leading brands, the incidence of variant colour names increased from 49.5 to 79.3%. CONCLUSIONS: New brands and variants were not inhibited by the introduction of plain packaging in Australia. After plain packaging, leading brand variant numbers expanded by 9 to 116 and colour variant names increased by 73.6% and became the norm-lighter colours (blue, gold and silver) dominated, perpetuating notions of less harmful cigarettes. [Correction added on 09 September 2016, after first online publication: The figures in the last sentence of the Abstract are now corrected from 'expanded by 116' to 'expanded by 9 to 116'.]. PMID- 27557864 TI - Ribosomal dimerization factor YfiA is the major protein synthesized after abrupt glucose depletion in Lactococcus lactis. AB - We analysed the response of the model bacterium Lactococcus lactis to abrupt depletion of glucose after several generations of exponential growth. Glucose depletion resulted in a drastic drop in the energy charge accompanied by an extremely low GTP level and an almost total arrest of protein synthesis. Strikingly, the cell prioritized the continued synthesis of a few proteins, of which the ribosomal dimerization factor YfiA was the most highly expressed. Transcriptome analysis showed no immediate decrease in total mRNA levels despite the lowered nucleotide pools and only marginally increased levels of the yfiA transcript. Severe up-regulation of genes in the FruR, CcpA, ArgR and AhrC regulons were consistent with a downshift in carbon and energy source. Based upon the results, we suggest that transcription proceeded long enough to record the transcriptome changes from activation of the FruR, CcpA, ArgR and AhrC regulons, while protein synthesis stopped due to an extremely low GTP concentration emerging a few minutes after glucose depletion. The yfiA deletion mutant exhibited a longer lag phase upon replenishment of glucose and a faster death rate after prolonged starvation supporting that YfiA-mediated ribosomal dimerization is important for keeping long-term starved cells viable and competent for growth initiation. PMID- 27557865 TI - A randomised clinical trial to evaluate the effect of a 67 % sodium bicarbonate containing dentifrice on 0.2 % chlorhexidine digluconate mouthwash tooth staining. AB - BACKGROUND: Gingivitis can develop as a reaction to dental plaque. It can be limited by curtailing plaque build-up through actions including tooth brushing and the use of medicinal mouthwashes, such as those containing chlorhexidine digluconate (CHX), that can reach parts of the mouth that may be missed when brushing. This study aimed to compare dental stain control of twice-daily brushing with a sodium fluoride (NaF) dentifrice containing 67 % sodium bicarbonate (NaHCO3) or a commercially available NaF silica dentifrice without NaHCO3, while using a mouthwash containing 0.2 % CHX. METHODS: This was a 6-week, randomised, two-site, examiner-blind, parallel-group study in healthy subjects with at least 'mild' stain levels on the facial surfaces of >=4 teeth and >=15 bleeding sites. Assessment was via modified Lobene Stain Index (MLSI), the score being the mean of stain intensity multiplied by area (MLSI [IxA]). RESULTS: One hundred and fifty of 160 randomised subjects completed the study. There were no significant differences in Overall (facial and lingual) MLSI (IxA) scores between dentifrices. The Facial MLSI (IxA) was statistically significant at 6 weeks, favouring the 67 % NaHCO3 dentifrice (p = 0.0404). Post-hoc analysis, conducted due to a significant site interaction, found significant differences for all MLSI scores in favour of the 67 % NaHCO3 dentifrice at Site 1 (both weeks) but not Site 2. CONCLUSIONS: No overall significant differences were found between a 67 and 0 % NaHCO3 dentifrice in controlling CHX stain; a significant difference on facial surfaces suggests advantage of the former on more accessible surfaces. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT01962493 ) on 10 October 2013 and was funded by GSK Consumer Healthcare. PMID- 27557866 TI - Comparative genomics reveals convergent rates of evolution in ant-plant mutualisms. AB - Symbiosis-the close and often long-term interaction of species-is predicted to drive genome evolution in a variety of ways. For example, parasitic interactions have been shown to increase rates of molecular evolution, a trend generally attributed to the Red Queen Hypothesis. However, it is much less clear how mutualisms impact the genome, as both increased and reduced rates of change have been predicted. Here we sequence the genomes of seven species of ants, three that have convergently evolved obligate plant-ant mutualism and four closely related species of non-mutualists. Comparing these sequences, we investigate how genome evolution is shaped by mutualistic behaviour. We find that rates of molecular evolution are higher in the mutualists genome wide, a characteristic apparently not the result of demography. Our results suggest that the intimate relationships of obligate mutualists may lead to selective pressures similar to those seen in parasites, thereby increasing rates of evolution. PMID- 27557869 TI - Rapid annotation of nifH gene sequences using classification and regression trees facilitates environmental functional gene analysis. AB - The nifH gene is a widely used molecular proxy for studying nitrogen fixation. Phylogenetic classification of nifH gene sequences is an essential step in diazotroph community analysis that requires a fast automated solution due to increasing size of environmental sequence libraries and increasing yield of nifH sequences from high-throughput technologies. A novel approach to rapidly classify nifH amino acid sequences into well-defined phylogenetic clusters that provides a common platform for comparative analysis across studies is presented. Phylogenetic group membership can be accurately predicted with decision tree-type statistical models that identify and utilize signature residues in the amino acid sequences. Our classification models were trained and evaluated with a publicly available and manually curated nifH gene database containing cluster annotations. Model-independent sequence sets from diverse ecosystems were used for further assessment of the models' prediction accuracy. The utility of this novel sequence binning approach was demonstrated in a comparative study where joint treatment of diazotroph assemblages from a wide range of habitats identified habitat-specific and widely-distributed diazotrophs and revealed a marine - terrestrial distinction in community composition. Our rapid and automated phylogenetic cluster assignment circumvents extensive phylogenetic analysis of nifH sequences; hence, it saves substantial time and resources in nitrogen fixation studies. PMID- 27557868 TI - Tunable Crosslinked Cell-Derived Extracellular Matrix Guides Cell Fate. AB - Extracellular matrix (ECM), comprised of multiple cues (chemical, physiomechanical), provides a niche for cell attachment, migration, and differentiation. Given that different cells give rise to distinct physiological milieus, the role of such microenvironmental cues on various cells has been well studied. Particularly, the effect of various physiomechanical factors on stem cell lineage has been resolved into individual variables via ECM protein-coated polymeric systems. Such platforms, while providing a reductionist approach as a means to remove any confounding factors, unfortunately fall short of capturing the full biophysical scope of the natural microenvironment. Herein, the use of a cell-derived ECM platform is reported in which its crosslinking density is tunable; varying concentrations (0, 0.5, 1, 2% w/v) of genipin (GN), a naturally derived crosslinker with low toxicity, are used to form inter- and intrafibril crosslinks. ECM crosslinking produces GN concentration-dependent changes in ECM stiffness (<0.1-9.4 kPa), roughness (96-280 nm), and chemical composition (100 60% amine content). The effect of the various crosslinked ECM profiles on human mesenchymal stem cell differentiation, vascular morphogenesis, and cardiomyogenesis are then evaluated. Taken together, this study demonstrates that tunable crosslinked cell-derived ECM platform is capable of providing a comprehensive physiological platform, and envisions its use in future tissue engineering applications. PMID- 27557867 TI - Behavioural and neurological symptoms accompanied by cellular neuroinflammation in IL-10-deficient mice infected with Plasmodium chabaudi. AB - BACKGROUND: Cerebral malaria is one of the most severe complications of Plasmodium falciparum infection and occurs mostly in young African children. This syndrome results from a combination of high levels of parasitaemia and inflammation. Although parasite sequestration in the brain is a feature of the human syndrome, sequestering strains do not uniformly cause severe malaria, suggesting interplay with other factors. Host genetic factors such as mutations in the promoters of the cytokines IL-10 and TNF are also clearly linked to severe disease. Plasmodium chabaudi, a rodent malaria parasite, leads to mild illness in wildtype animals. However, IL-10(-/-) mice respond to parasite with increased levels of pro-inflammatory cytokines IFN-gamma and TNF, leading to lethal disease in the absence of sequestration in the brain. These mice also exhibit cerebral symptoms including gross cerebral oedema and haemorrhage, allowing study of these critical features of disease without the influence of sequestration. METHODS: The neurological consequences of P. chabaudi infection were investigated by performing a general behavioural screen (SHIRPA). The immune cell populations found in the brain during infection were also analysed using flow cytometry and confocal microscopy. RESULTS: IL-10(-/-) mice suffer significant declines in behavioural and physical capacities during infection compared to wildtype. In addition, grip strength and pain sensitivity were affected, suggestive of neurological involvement. Several immune cell populations were identified in the perfused brain on day 7 post-infection, suggesting that they are tightly adherent to the vascular endothelium, or potentially located within the brain parenchyma. There was an increase in both inflammatory monocyte and resident macrophage (CD11b(hi), CD45(+), MHCII(+), Ly6C(+/-)) numbers in IL-10(-/-) compared to wildtype animals. In addition, the activation state of all monocytes and microglia (CD11b(int), CD45(-), MHC-II(+)) were increased. T cells making IFN gamma were also identified in the brain, but were localized within the vasculature, and not the parenchyma. CONCLUSIONS: These studies demonstrate exacerbated neuroinflammation concurrent with development of behavioural symptoms in P. chabaudi infection of IL-10(-/-) animals. PMID- 27557870 TI - Ultrastructural and developmental features of the tessellated endoskeleton of elasmobranchs (sharks and rays). AB - The endoskeleton of elasmobranchs (sharks and rays) is comprised largely of unmineralized cartilage, differing fundamentally from the bony skeletons of other vertebrates. Elasmobranch skeletons are further distinguished by a tessellated surface mineralization, a layer of minute, polygonal, mineralized tiles called tesserae. This 'tessellation' has defined the elasmobranch group for more than 400 million years, yet the limited data on development and ultrastructure of elasmobranch skeletons (e.g. how tesserae change in shape and mineral density with age) have restricted our abilities to develop hypotheses for tessellated cartilage growth. Using high-resolution, two-dimensional and three-dimensional materials and structural characterization techniques, we investigate an ontogenetic series of tessellated cartilage from round stingray Urobatis halleri, allowing us to define a series of distinct phases for skeletal mineralization and previously unrecognized features of tesseral anatomy. We show that the distinct tiled morphology of elasmobranch calcified cartilage is established early in U. halleri development, with tesserae forming first in histotroph embryos as isolated, globular islets of mineralized tissue. By the sub-adult stage, tesserae have increased in size and grown into contact with one another. The intertesseral contact results in the formation of more geometric (straight-edged) tesseral shapes and the development of two important features of tesseral anatomy, which we describe here for the first time. The first, the intertesseral joint, where neighboring tesserae abut without appreciable overlapping or interlocking, is far more complex than previously realized, comprised of a convoluted bearing surface surrounded by areas of fibrous attachment. The second, tesseral spokes, are lamellated, high-mineral density features radiating outward, like spokes on a wheel, from the center of each tessera to its joints with its neighbors, likely acting as structural reinforcements of the articulations between tesserae. As tesserae increase in size during ontogeny, spokes are lengthened via the addition of new lamellae, resulting in a visually striking mineralization pattern in the larger tesserae of older adult skeletons when viewed with scanning electron microscopy (SEM) in backscatter mode. Backscatter SEM also revealed that the cell lacunae in the center of larger tesserae are often filled with high mineral density material, suggesting that when intratesseral cells die, cell-regulated inhibition of mineralization is interrupted. Many of the defining ultrastructural details we describe relate to local variation in tissue mineral density and support previously proposed accretive growth mechanisms for tesserae. High resolution micro-computed tomography data indicate that some tesseral anatomical features we describe for U. halleri are common among species of all major elasmobranch groups despite large variation in tesseral shape and size. We discuss hypotheses about how these features develop, and compare them with other vertebrate skeletal tissue types and their growth mechanisms. PMID- 27557871 TI - SuFEx Click: New Materials from SOx F and Silyl Ethers. AB - New forms of click chemistry present new opportunities in materials science. Sulfur(VI) fluoride exchange (SuFEx) is a recently discovered click reaction between molecules containing SOx F groups and silyl ethers, two functionalities that are orthogonal to all other known click chemistries, that generates sulfate or sulfonate connections upon the addition of certain organobases or fluoride sources. SuFEx also has several important advantages over other click reactions in that it is insensitive to ambient oxygen and water, and its precursor materials, especially SOx F, are chemically, UV, and thermally inert. This Concept article focuses on the unique reactivity of SuFEx and its relation to building high molecular weight polymers and surface coatings, both of which make it a powerful new tool for materials science. PMID- 27557873 TI - Abstracts of the 9th Congress of the European Academy of Andrology, 21 - 23 September 2016, Rotterdam, Netherlands. PMID- 27557872 TI - Investigation of mechanism: spoof SPPs on periodically textured metal surface with pyramidal grooves. AB - In microwave and terahertz frequency band, a textured metal surface can support spoof surface plasmon polaritons (SSPPs). In this paper, we explore a SSPPs waveguide composed of a metal block with pyramidal grooves. Under the deep subwavelength condition, theoretical formulas for calculation of dispersion relations are derived based on the modal expansion method (MEM). Using the obtained formulas, a general analysis is given about the properties of the SSPPs in the waveguides with upright and downward pyramidal grooves. It is demonstrated that the SSPPs waveguides with upright pyramidal grooves give better field confinement. Numerical simulations are used to check the theoretical analysis and show good agreement with the analytical results. In addition, the group velocity of the SSPPs propagating along the waveguide is explored and two structures are designed to show how to trap the SSPPs on the metal surface. The calculation methodology provided in this paper can also be used to deal with the SSPPs waveguides with irregular grooves. PMID- 27557874 TI - Chapter 8 - Life style. PMID- 27557875 TI - Asymptomatic hepatic portal venous gas with gastric emphysema as a chronic complication of gastrostomy tube placement: a case report. AB - BACKGROUND: Percutaneous endoscopic gastrostomy feeding is widely used as a route for enteral feeding for patients with impaired swallowing ability, particularly in older patients. Hepatic portal venous gas is a condition that may arise from several causes. Hepatic portal venous gas that develops after an endoscopic procedure is generally reported to be nonfatal, yet there is little information available concerning the characteristics of hepatic portal venous gas as a chronic complication of percutaneous endoscopic gastrostomy feeding. CASE PRESENTATION: We experienced a case of hepatic portal venous gas that happened to be detected in an 81-year-old Japanese man with long-term percutaneous endoscopic gastrostomy use who was admitted to our hospital with aspiration pneumonia. While aspiration pneumonia was treated with antibiotics and suspension of tube feedings, he recovered from hepatic portal venous gas without any treatment. CONCLUSIONS: The presence of a percutaneous endoscopic gastrostomy tube may have induced hepatic portal venous gas through a mechanism in which vomiting led to increased abdominal pressure and eventually gastric emphysema. This case suggests that hepatic portal venous gas without any signs of bowel ischemia or emphysematous gastritis can resolve without treatment, which is a finding that could be helpful for clinicians who deal with those supported by percutaneous endoscopic gastrostomy feeding. PMID- 27557876 TI - Assessing bleeding risk in 4824 Asian patients with atrial fibrillation: The Beijing PLA Hospital Atrial Fibrillation Project. AB - The risks of major bleeding and intracranial hemorrhage (ICH) are higher in Asian patients with atrial fibrillation (AF) compared to non-Asians. We aimed to investigate risk factors for bleeding, and validate the predictive value of available bleeding risk scores (mOBRI, HEMORR2HAGES, Shireman, HAS-BLED, ATRIA and ORBIT) in a large cohort of Chinese inpatients with AF. Using hospital electronic medical databases, we identified 4824 AF patients (mean age 67 years; 34.9% female) from January 1, 1995 to May 30, 2015, with median (interquartile) in-hospital days of 10 (7-16) days. On multivariate analysis, prior bleeds, vascular disease, anemia, prior stroke, and liver dysfunction were independent risk factors of major bleeding (all p < 0.05). C-statistics (95%CI) of the HAS BLED score were 0.72 (0.65-0.79) for major bleeding events and 0.83 (0.75-0.91) for ICH (all p < 0.001). Compared to other risk scores, the HAS-BLED score was significantly better in predicting major bleeding events (Delong test, all P < 0.05, apart from mOBRI, HEMORR2HAGES) and ICH (all p < 0.05), and additionally, resulted in a net reclassification improvement (NRI) of 17.1-65.5% in predicting major bleeding events and 29.5-67.3% in predicting ICH (all p < 0.05). We conclude that the HAS-BLED score had the best predictive and discriminatory ability for major bleeding and ICH in an Asian/Chinese AF population. PMID- 27557877 TI - Epigallocatechin-3-gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing. AB - In non-healing wounds, mesenchymal stem cell (MSC)-based therapies have the potential to activate a series of coordinated cellular processes, including angiogenesis, inflammation, cell migration, proliferation and epidermal terminal differentiation. As pro-inflammatory reactions play indispensable roles in initiating wound repair, sustained and prolonged inflammation exhibit detrimental effects on skin wound closure. We investigated the feasibility of using an antioxidant agent epigallocatechin-3-gallate (EGCG), along with MSCs, to improve wound repair through their immunomodulatory actions. In a rat model of wound healing, a single dose of EGCG at 10 mg/kg increased the efficiency of MSC induced skin wound closure. Twenty days after the wound induction, MSC treatment significantly enhanced the epidermal thickness, which was further increased by EGCG administration. Consistently, the highest extent of growth factors upregulation for neovascularization induction was seen in the animals treated by both MSCs and EGCG, associated with a potent anti-scarring effect throughout the healing process. Finally, expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL 6, in the wound area were reduced by MSCs, and this reduction was further potentiated by EGCG co-administration. EGCG, together with MSCs, can promote skin wound healing likely through their combinational effects in modulating chronic inflammation. PMID- 27557878 TI - The risk of late or advanced presentation of HIV infected patients is still high, associated factors evolve but impact on overall mortality is vanishing over calendar years: results from the Italian MASTER Cohort. AB - BACKGROUND: We aimed at evaluating frequency and factors associated with late presentation and advanced HIV disease and excess risk of death due to these conditions from 1985 to 2013 among naive HIV infected patients enrolled in the Italian MASTER Cohort. METHODS: All antiretroviral naive adults with available CD4+ T cell count after diagnosis of HIV infection were included. Multivariable logistic regression analysis investigated factors associated either with late presentation or advanced HIV disease. Probabilities of survival were estimated both at year-1 and at year-5 according to the Kaplan-Meier method. Flexible parametric models were used to evaluate changes in risk of death overtime according to late presentation and advanced HIV disease. The analyses were stratified for calendar periods. RESULTS: 19,391 patients were included (54 % were late presenters and 37.6 % were advanced presenters). At multivariable analysis, the following factors were positively associated with late presentation: male gender (OR = 1.29), older age (>=55 years vs. <25 years; OR = 7.45), migration (OR = 1.54), and heterosexual risk factor for HIV acquisition (OR = 1.52) or IDU (OR = 1.27) compared to homosexual risk. Survival rates at year-5 increased steadily and reached 92.1 % for late presenters vs. 97.4 % for non-late presenters enrolled in the period 2004-2009. Using flexible parametric models we found a sustained reduction of hazard ratios over time for any cause deaths between late and non-late presenters over time. Similar results were found for advanced HIV disease. CONCLUSION: Screening polices need to be urgently implemented, particularly in most-at-risk categories for late presentation, such as migrants, older patients and those with heterosexual intercourse or IDU as risk factors for HIV acquisition. Although in recent years the impact of late presentation on survival decreased, about 10 % of patients diagnosed in more recent years remains at increased risk of death over a long-term follow-up. PMID- 27557879 TI - Urinary kidney injury molecules in children with febrile seizures. AB - OBJECTIVE: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and liver type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time. METHODS: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons. RESULTS: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 +/- 9.8; 6.7 +/- 4.0, respectively; p < 0.001), NAG/Cr (0.55 +/- 0.29; 0.21 +/- 0.16, p < 0.001), and L-FABP/Cr (4.85 +/- 2.93; 1.74 +/- 1.16, p < 0.001). CONCLUSION: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients. PMID- 27557880 TI - An ensemble framework for identifying essential proteins. AB - BACKGROUND: Many centrality measures have been proposed to mine and characterize the correlations between network topological properties and protein essentiality. However, most of them show limited prediction accuracy, and the number of common predicted essential proteins by different methods is very small. RESULTS: In this paper, an ensemble framework is proposed which integrates gene expression data and protein-protein interaction networks (PINs). It aims to improve the prediction accuracy of basic centrality measures. The idea behind this ensemble framework is that different protein-protein interactions (PPIs) may show different contributions to protein essentiality. Five standard centrality measures (degree centrality, betweenness centrality, closeness centrality, eigenvector centrality, and subgraph centrality) are integrated into the ensemble framework respectively. We evaluated the performance of the proposed ensemble framework using yeast PINs and gene expression data. The results show that it can considerably improve the prediction accuracy of the five centrality measures individually. It can also remarkably increase the number of common predicted essential proteins among those predicted by each centrality measure individually and enable each centrality measure to find more low-degree essential proteins. CONCLUSIONS: This paper demonstrates that it is valuable to differentiate the contributions of different PPIs for identifying essential proteins based on network topological characteristics. The proposed ensemble framework is a successful paradigm to this end. PMID- 27557881 TI - Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing. AB - In this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time, and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction, and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing. PMID- 27557882 TI - Formation mechanism of guided resonances and bound states in the continuum in photonic crystal slabs. AB - We develop a formalism, based on the mode expansion method, to describe the guided resonances and bound states in the continuum (BICs) in photonic crystal slabs with one-dimensional periodicity. This approach provides analytic insights to the formation mechanisms of these states: the guided resonances arise from the transverse Fabry-Perot condition, and the divergence of the resonance lifetimes at the BICs is explained by a destructive interference of radiation from different propagating components inside the slab. We show BICs at the center and on the edge of the Brillouin zone protected by symmetry, BICs at generic wave vectors not protected by symmetry, and the annihilation of BICs at low-symmetry wave vectors. PMID- 27557883 TI - An electrophysiological dissociation of craving and stimulus-dependent attentional capture in smokers. AB - It has been suggested that over the course of an addiction, addiction-related stimuli become highly salient in the environment, thereby capturing an addict's attention. To assess these effects neurally in smokers, and how they interact with craving, we recorded electroencephalography (EEG) in two sessions: one in which participants had just smoked (non-craving), and one in which they had abstained from smoking for 3 h (craving). In both sessions, participants performed a visual-search task in which two colored squares were presented to the left and right of fixation, with one color being the target to which they should shift attention and discriminate the locations of two missing corners. Task irrelevant images, both smoking-related and non-smoking-related, were embedded in both squares, enabling the shift of spatial attention to the target to be examined as a function of the addiction-related image being present or absent in the target, the distractor, or both. Behaviorally, participants were slower to respond to targets containing a smoking-related image. Furthermore, when the target contained a smoking-related image, the neural responses indicated that attention had been shifted less strongly to the target; when the distractor contained a smoking-related image, the shift of attention to the contralateral target was stronger. These effects occurred independently of craving and suggest that participants were actively avoiding the smoking-related images. Together, these results provide an electrophysiological dissociation between addiction related visual-stimulus processing and the neural activity associated with craving. PMID- 27557884 TI - The fate of unattended stimuli and emotional habituation: Behavioral interference and cortical changes. AB - The interference produced by the viewing of emotional distractors has been interpreted as evidence that emotional cues are processed in a fairly mandatory fashion, and that they divert attention from the primary ongoing task. However, few studies have examined how behavioral emotional interference varies with repeated presentation of the same emotional distractors. In two experiments, while participants were engaged in a parity judgment task, we investigated the effects of repetition of task-irrelevant emotional pictures, as reflected in both behavioral interference (Experiments 1 and 2) and neural activity (Experiment 2). Both experiments showed that the slowing of reaction times that was observed when viewing emotional, compared to neutral, scenes disappeared after only a few repetitions, suggesting diminished attention allocation to repeated emotional pictures. Conversely, in Experiment 2, neural correlates of picture processing revealed that the late positive potential (LPP) amplitude continued to be enhanced for emotional, compared to neutral, distractors despite picture repetition and the presence of a concurrent task. Altogether, these findings suggest that while evaluative processes are mandatory, and continue to engage cortico-limbic appetitive and defensive systems even after massive repetition, as suggested by the affective modulation of the LPP, attentional processes are not necessary after several repetitions of the same stimulus, as indicated by the rapid decline of behavioral emotional interference. PMID- 27557885 TI - Putative EEG measures of social anxiety: Comparing frontal alpha asymmetry and delta-beta cross-frequency correlation. AB - The goal of the present study was to examine whether frontal alpha asymmetry and delta-beta cross-frequency correlation during resting state, anticipation, and recovery are electroencephalographic (EEG) measures of social anxiety. For the first time, we jointly examined frontal alpha asymmetry and delta-beta correlation during resting state and during a social performance task in high (HSA) versus low (LSA) socially anxious females. Participants performed a social performance task in which they first watched and evaluated a video of a peer, and then prepared their own speech. They believed that their speech would be videotaped and evaluated by a peer. We found that HSA participants showed significant negative delta-beta correlation as compared to LSA participants during both anticipation of and recovery from the stressful social situation. This negative delta-beta correlation might reflect increased activity in subcortical brain regions and decreased activity in cortical brain regions. As we hypothesized, no group differences in delta-beta correlation were found during the resting state. This could indicate that a certain level of stress is needed to find EEG measures of social anxiety. As for frontal alpha asymmetry, we did not find any group differences. The present frontal alpha asymmetry results are discussed in relation to the evident inconsistencies in the frontal alpha asymmetry literature. Together, our results suggest that delta-beta correlation is a putative EEG measure of social anxiety. PMID- 27557886 TI - Myelin repair by transplantation of myelin-forming cells in globoid cell leukodystrophy. AB - Globoid cell leukodystrophy (GLD), or Krabbe disease, is a devastating demyelinating disease that affects both the central and peripheral nervous systems. It is caused by genetic deficiency in the activity of a lysosomal enzyme, galactocerebrosidase (GALC), which is necessary for the maintenance of myelin. Hematopoietic stem cell transplantation (HSCT) including umbilical cord stem cell transplantation is the only effective therapy available to date. HSCT significantly prolongs the life span of patients with GLD when performed before disease onset, although it is not curative. In HSCT, infiltrating donor-derived macrophages are thought to indirectly supply the enzyme (called "cross correction") to the host's myelinating cells. Given the limitation in treating GLD, it is hypothesized that remyelinating demyelinated axons with GALC-competent myelinating cells by transplantation will result in more stable myelination than endogenous myelin repair supported by GALC cross-correction. Transplantation of myelin-forming cells in a variety of animal models of dysmyelinating and demyelinating disorders suggests that this approach is promising in restoring saltatory conduction and protecting neurons by providing new healthy myelin. However, GLD is one of the most challenging diseases in terms of the aggressiveness of the disease and widespread pathology. Experimental transplantation of myelin-forming cells in the brain of a mouse model of GLD has been only modestly effective to date. Thus, a practical strategy for myelin repair in GLD would be to combine the rapid and widespread cross-correction of GALC by HSCT with the robust, stable myelination provided by transplanted GALC producing myelin-forming cells. This short review will discuss such possibilities. (c) 2016 Wiley Periodicals, Inc. PMID- 27557888 TI - In vitro biometry of a human spherophakia. PMID- 27557889 TI - Selectivity Control in the Tandem Aromatization of Bio-Based Furanics Catalyzed by Solid Acids and Palladium. AB - Bio-based furanics can be aromatized efficiently by sequential Diels-Alder (DA) addition and hydrogenation steps followed by tandem catalytic aromatization. With a combination of zeolite H-Y and Pd/C, the hydrogenated DA adduct of 2 methylfuran and maleic anhydride can thus be aromatized in the liquid phase and, to a certain extent, decarboxylated to give high yields of the aromatic products 3-methylphthalic anhydride and o- and m-toluic acid. Here, it is shown that a variation in the acidity and textural properties of the solid acid as well as bifunctionality offers a handle on selectivity toward aromatic products. The zeolite component was found to dominate selectivity. Indeed, a linear correlation is found between 3-methylphthalic anhydride yield and the product of (strong acid/total acidity) and mesopore volume of H-Y, highlighting the need for balanced catalyst acidity and porosity. The efficient coupling of the dehydration and dehydrogenation steps by varying the zeolite-to-Pd/C ratio allowed the competitive decarboxylation reaction to be effectively suppressed, which led to an improved 3-methylphthalic anhydride/total aromatics selectivity ratio of 80 % (89 % total aromatics yield). The incorporation of Pd nanoparticles in close proximity to the acid sites in bifunctional Pd/H-Y catalysts also afforded a flexible means to control aromatic products selectivity, as further demonstrated in the aromatization of hydrogenated DA adducts from other diene/dienophile combinations. PMID- 27557890 TI - Wearable Thermocells Based on Gel Electrolytes for the Utilization of Body Heat. AB - Converting body heat into electricity is a promising strategy for supplying power to wearable electronics. To avoid the limitations of traditional solid-state thermoelectric materials, such as frangibility and complex fabrication processes, we fabricated two types of thermogalvanic gel electrolytes with positive and negative thermo-electrochemical Seebeck coefficients, respectively, which correspond to the n-type and p-type elements of a conventional thermoelectric generator. Such gel electrolytes exhibit not only moderate thermoelectric performance but also good mechanical properties. Based on these electrolytes, a flexible and wearable thermocell was designed with an output voltage approaching 1 V by utilizing body heat. This work may offer a new train of thought for the development of self-powered wearable systems by harvesting low-grade body heat. PMID- 27557887 TI - Adenosine production: a common path for mesenchymal stem-cell and regulatory T cell-mediated immunosuppression. AB - Adenosine is an important molecule that exerts control on the immune system, by signaling through receptors lying on the surface of immune cells. This nucleotide is produced, in part, by the action of the ectoenzymes CD39 and CD73. Interestingly, these proteins are expressed on the cell surface of regulatory T cells (Tregs) and mesenchymal stromal cells (MSCs)-two cell populations that have emerged as potential therapeutic tools in the field of cell therapy. In fact, the production of adenosine constitutes a mechanism used by both cell types to control the immune response. Recently, great scientific progress was obtained regarding the role of adenosine in the inflammatory environment. In this context, the present review focuses on the advances related to the impact of adenosine production over the immune modulatory activity of Tregs and MSCs, and how this nucleotide controls the biological functions of these cells. Finally, we mention the main challenges and hurdles to bring such molecule to clinical settings. PMID- 27557891 TI - Outcome and risk factors of cesarean delivery with and without cesarean myomectomy in women with uterine myomatas. AB - AIM: To evaluate the outcome of a cesarean myomectomy (CM) versus a cesarean delivery (CD) alone in women with uterine myomas and the risk factors for adverse outcomes. METHODS: A retrospective cohort study of all women undergoing CDs with uterine leiomyomatas and singleton pregnancies was performed. Patients with known risk factors for hemorrhage were excluded. Measured adverse outcome parameters included estimated blood loss, drop in hemoglobin levels (pre/postoperatively), operation time, and the use of additional uterotonics. Outcome parameters of women with CM were compared to women with CD alone. Possible risk factors for adverse outcomes were analyzed in a multivariate regression analysis. Evaluated risk factors for CM were according to localization and type of myomatas, the myoma size, BMI >=30 kg/m2, age >=40 years, fetal weight >=4 kg, repeat CD, and unplanned CD in the first stage of labor. The influence of localization and myoma type were further analyzed in a subgroup analysis. RESULTS: Of the 162 women with uterine myomatas during CD, 48 underwent CM and were analyzed. Overall, CM was not associated with adverse outcomes. Independent of a concomitant myomectomy, a large myoma size of >=5 cm was associated with an increased blood loss of >=500 ml (adj. OR 2.7 CI 95 % 1.2-6.2, p = 0.02), and women >=40 years of age had a significant postoperative drop in hemoglobin (adj. OR 2.4 CI 95 % 1.0-5.4, p = 0.04). In the univariate subgroup analysis, CM of multiple myomatas was associated with an increased blood loss and an increased operation time compared to women with multiple myomatas and CD alone. Prolonged operation times were also observed in women with pedunculated and subserosal myomatas with concomitant myomectomy. There were no cases of hysterectomy or blood transfusions. CONCLUSION: CM performed by an experienced obstetrician can be safe in selected patients who are without additional preexisting risk factors. Risk factors that are associated with increased blood loss in women with uterine leiomyomatas include a larger size of the leiomyoma (>=5 cm) and a maternal age of >=40 years. PMID- 27557892 TI - Change in serum TSH levels within the reference range was associated with variation of future blood pressure: a 5-year follow-up study. AB - Controversy exists on the relationship between serum thyrotropin (TSH) and blood pressure, and only a few prospective studies are available up to now. The study aimed to investigate the association between serum TSH within the reference range and blood pressure through a 5-year follow-up study. A total of 623 subjects with normal TSH were followed up for 5 years, including the measurement of demographic data, blood pressure, height, weight and serum TSH. Finally, 531 subjects were included in this prospective study. Body mass index (BMI), prevalence of hypertension, and systolic and diastolic blood pressure were all higher at follow up than at baseline. Adjusted for age, gender, smoking status, BMI and homoeostasis model assessment of insulin resistance (HOMA-IR) at baseline, multiple linear regression analyses found no relationship between serum TSH at baseline and levels of blood pressure at follow-up, but the changes in serum TSH levels during follow-up was positively associated with the changes in systolic blood pressure (B=2.134, P<0.05), which became more significant in women but not significant in men. The change of systolic blood pressure in group of TSH increase >0.5 mIU l-1 was significantly higher than in group of TSH decrease >0.5 mIU l-1 within reference, after adjusting for age, gender, smoking status, BMI and HOMA-IR at baseline. This result became more significant in women, but no statistical significance was observed in men. Co-variation with serum TSH levels and blood pressure was observed during 5-year follow-up among people with normal TSH. PMID- 27557893 TI - Racial/Ethnic Discrimination and Adolescents' Well-Being: The Role of Cross Ethnic Friendships and Friends' Experiences of Discrimination. AB - There is an extensive body of work documenting the negative socioemotional and academic consequences of perceiving racial/ethnic discrimination during adolescence, but little is known about how the larger peer context conditions such effects. Using peer network data from 252 eighth graders (85% Latino, 11% African American, 5% other race/ethnicity), the present study examined the moderating role of cross-ethnic friendships and close friends' experiences of discrimination in the link between adolescents' perceptions of discrimination and well-being. Cross-ethnic friendships and friends' experiences of discrimination generally served a protective role, buffering the negative effects of discrimination on both socioemotional well-being and school outcomes. Overall, results highlight the importance of considering racial/ethnic-related aspects of adolescents' friendships when studying interpersonal processes closely tied to race/ethnicity. PMID- 27557894 TI - Sensory input attenuation allows predictive sexual response in yeast. AB - Animals are known to adjust their sexual behaviour depending on mate competition. Here we report similar regulation for mating behaviour in a sexual unicellular eukaryote, the budding yeast Saccharomyces cerevisiae. We demonstrate that pheromone-based communication between the two mating types, coupled to input attenuation by recipient cells, enables yeast to robustly monitor relative mate abundance (sex ratio) within a mixed population and to adjust their commitment to sexual reproduction in proportion to their estimated chances of successful mating. The mechanism of sex-ratio sensing relies on the diffusible peptidase Bar1, which is known to degrade the pheromone signal produced by mating partners. We further show that such a response to sexual competition within a population can optimize the fitness trade-off between the costs and benefits of mating response induction. Our study thus provides an adaptive explanation for the known molecular mechanism of pheromone degradation in yeast. PMID- 27557895 TI - The CHAP-EMS health promotion program: a qualitative study on participants' views of the role of paramedics. AB - BACKGROUND: Expanded roles for paramedics, commonly termed community paramedicine, are becoming increasingly common. Paramedics working in community paramedicine roles represent a distinct departure away from the traditional emergency paradigm of paramedic services. Despite this, little research has addressed how community paramedics are perceived by their clients. METHODS: This study took an interpretivist qualitative approach to examine participants' perceptions of paramedics providing a community paramedicine program, named the Community Health Assessment Program through Emergency Medical Services (CHAP EMS). Both participant observation and semi-structured interviews conducted with program participants were used to gain insight into the on-the-ground experiences of the program. Thematic analysis was employed to analyze all data. RESULTS: Three themes emerged: i) Caring and trusting relationships; ii) paramedics as health advocates; iii) the added value of EMS skills. Paramedics were perceived by residents as having dual identities: first in a novel role as health advocates and secondly in a traditional role as emergency experts despite lacking contextual features associated with emergency response. CONCLUSIONS: From this exploratory, qualitative study we present an emerging framework in which to conceptualize paramedic roles in community paramedicine settings. Future research should address the saliency of these roles in different contexts and how these roles relate to paramedic practice. PMID- 27557896 TI - Alzheimer-related protein APL-1 modulates lifespan through heterochronic gene regulation in Caenorhabditis elegans. AB - Alzheimer's disease (AD) is an age-associated disease. Mutations in the amyloid precursor protein (APP) may be causative or protective of AD. The presence of two functionally redundant APP-like genes (APLP1/2) has made it difficult to unravel the biological function of APP during aging. The nematode Caenorhabditis elegans contains a single APP family member, apl-1. Here, we assessed the function of APL 1 on C. elegans' lifespan and found tissue-specific effects on lifespan by overexpression of APL-1. Overexpression of APL-1 in neurons causes lifespan reduction, whereas overexpression of APL-1 in the hypodermis causes lifespan extension by repressing the function of the heterochronic transcription factor LIN-14 to preserve youthfulness. APL-1 lifespan extension also requires signaling through the FOXO transcription factor DAF-16, heat-shock factor HSF-1, and vitamin D-like nuclear hormone receptor DAF-12. We propose that reinforcing APL-1 expression in the hypodermis preserves the regulation of heterochronic lin-14 gene network to improve maintenance of somatic tissues via DAF-16/FOXO and HSF-1 to promote healthy aging. Our work reveals a mechanistic link of how a conserved APP-related protein modulates aging. PMID- 27557897 TI - Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications. AB - This study evaluated the association of NOS3 polymorphisms with hypertension risk and complications. eNOS (G894T) SNP was performed by RT-PCR on 70 hypertensive patients (25 were hypertensive, 25 were hypertensive with CAD, and 20 were diabetic with hypertension) and 30 age- and gender-matched individuals. Lipid and glucose profile were assessed by standard colorimetric assay. Our results revealed that combination of (GT + TT) genotype and T allele significantly increases the risk of hypertension (OR = 3.86 and 4.33), respectively. Subgroup analysis showed significant association between CAD with eNOS (G894T) mutant genotype (P = 0.002) and allele frequency (P < 0.001). Moreover, the mutant homozygous and heterozygous eNOS genotype together were significantly associated with higher TC, LDLc, (P < 0.001), and TG (P = 0.001). Thus, hypercholesterolemia (P < 0.001 and OR = 12.48) increases the risk of hypertension among T carrier. These results indicated that the T carriers significantly increase hypertension risk and complication (CAD), mainly with hypercholesterolemia and in elderly. PMID- 27557899 TI - MicroRNA epigenetic signatures in human disease. AB - MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene. There is a strong connection between epigenome and miRNome, and any dysregulation of this complex system can result in various physiological and pathological conditions. In addition, miRNAs play an important role in toxicogenomics and may explain the relationship between toxicant exposure and tumorigenesis. The present review provides information on 63 miRNA genes shown to be epigenetically regulated in association with 21 diseases, including 11 cancer types: cardiac fibrosis, cardiovascular disease, preeclampsia, Hirschsprung's disease, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, temporal lobe epilepsy, autism, pulmonary fibrosis, melanoma, acute myeloid leukemia, chronic lymphocytic leukemia, colorectal, gastric, cervical, ovarian, prostate, lung, breast, and bladder cancer. The review revealed that hsa-miR-34a, hsa-miR-34b, and hsa-miR-34c are the most frequently reported epigenetically dysregulated miRNAs. There is a need to further study molecular mechanisms of various diseases to better understand the crosstalk between epigenetics and gene expression and to develop new therapeutic options and biomarkers. PMID- 27557898 TI - Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone. AB - Exposure to aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). Conflicting results have been found for the role of human sulfotransferase 1A1 (SULT1A1) contributing to the metabolic activation of aristolochic acid I (AAI) in vitro. We evaluated the role of human SULT1A1 in AA bioactivation in vivo after treatment of transgenic mice carrying a functional human SULT1A1-SULT1A2 gene cluster (i.e. hSULT1A1/2 mice) and Sult1a1( /-) mice with AAI and aristolochic acid II (AAII). Both compounds formed characteristic DNA adducts in the intact mouse and in cytosolic incubations in vitro. However, we did not find differences in AAI-/AAII-DNA adduct levels between hSULT1A1/2 and wild-type (WT) mice in all tissues analysed including kidney and liver despite strong enhancement of sulfotransferase activity in both kidney and liver of hSULT1A1/2 mice relative to WT, kidney and liver being major organs involved in AA metabolism. In contrast, DNA adduct formation was strongly increased in hSULT1A1/2 mice compared to WT after treatment with 3 nitrobenzanthrone (3-NBA), another carcinogenic aromatic nitro compound where human SULT1A1/2 is known to contribute to genotoxicity. We found no differences in AAI-/AAII-DNA adduct formation in Sult1a1(-/-) and WT mice in vivo. Using renal and hepatic cytosolic fractions of hSULT1A1/2, Sult1a1(-/-) and WT mice, we investigated AAI-DNA adduct formation in vitro but failed to find a contribution of human SULT1A1/2 or murine Sult1a1 to AAI bioactivation. Our results indicate that sulfo-conjugation catalysed by human SULT1A1 does not play a role in the activation pathways of AAI and AAII in vivo, but is important in 3-NBA bioactivation. PMID- 27557901 TI - Is chronic periodontitis premature in systemic lupus erythematosus patients? AB - The aim of this study was to compare the frequency and severity of chronic periodontitis (CP) in systemic lupus erythematosus (SLE) patients with individuals without rheumatic diseases. Seventy-five patients with SLE were compared to 75 individuals without rheumatic diseases (control group) matched for age, educational level, and income. The activity of SLE was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus evaluated SLE-related damage. Dental evaluation included measuring plaque index and parameters of periodontal disease (probing depth, clinical attachment level, and bleeding on probing). Fifty-one (68 %) SLE patients and 42 (56 %) control individuals had CP (p = 0.13). Periodontal status was similar in both groups. Considering only individuals with CP, SLE patients were younger than controls (40.7 +/- 9.8 versus 46.14 +/- 12.5 years of age, p = 0.02). CP was not associated with activity or therapeutics in SLE patients. Severity of periodontal parameters was similar in SLE patients and control subjects; however, CP occurred earlier in SLE patients. PMID- 27557900 TI - Estrogen Preserves Pulsatile Pulmonary Arterial Hemodynamics in Pulmonary Arterial Hypertension. AB - Pulmonary arterial hypertension (PAH) is caused by extensive pulmonary vascular remodeling that increases right ventricular (RV) afterload and leads to RV failure. PAH predominantly affects women; paradoxically, female PAH patients have better outcomes than men. The roles of estrogen in PAH remain controversial, which is referred to as "the estrogen paradox". Here, we sought to determine the role of estrogen in pulsatile pulmonary arterial hemodynamic changes and its impact on RV functional adaption to PAH. Female mice were ovariectomized and replenished with estrogen or placebo. PAH was induced with SU5416 and chronic hypoxia. In vivo hemodynamic measurements showed that (1) estrogen prevented loss of pulmonary vascular compliance with limited effects on the increase of pulmonary vascular resistance in PAH; (2) estrogen attenuated increases in wave reflections in PAH and limited its adverse effects on PA systolic and pulse pressures; and (3) estrogen maintained the total hydraulic power and preserved transpulmonary vascular efficiency in PAH. This study demonstrates that estrogen preserves pulmonary vascular compliance independent of pulmonary vascular resistance, which provides a mechanical mechanism for ability of estrogen to delay disease progression without preventing onset. The estrogenic protection of pulsatile pulmonary hemodynamics underscores the therapeutic potential of estrogen in PAH. PMID- 27557902 TI - Production of Mannitol from a High Concentration of Glucose by Candida parapsilosis SK26.001. AB - A novel strain, SK26.001, which can produce mannitol from a high concentration of glucose without the addition of fructose, was isolated from sugarcane juice. This strain was identified as Candida parapsilosis based on 18S ribosomal RNA (rRNA) sequence analysis and the morphological and physiological-biochemical characteristics of the strain. Under optimized fermentation conditions, the mannitol concentration in shake flasks reached 68.5 g/L. When batch fermentation was performed, the fed glucose was completely consumed after 72 h, resulting in a final mannitol concentration of 80.3 g/L. Fed-batch fermentation was then performed with glucose feed. During the fed-batch process, ammonia water was added to maintain the pH at 4.0. The mannitol concentration in the fermenter reached 97.1 g/L after 120 h, with a total glucose consumption of 284 g/L. PMID- 27557903 TI - Enhanced Performance of a Microbial Fuel Cell with a Capacitive Bioanode and Removal of Cr (VI) Using the Intermittent Operation. AB - This study investigated a system which simultaneously produced electricity and stored energy in the MFC integrated MnO2-modified capacitive bioanode. Compared to the noncapacitive anode, the maximum power density of MFC with MnO2-modified bioanode reached 16.47 W m-3, which was 3.5 times higher than that of the bare anode (4.71 W m-3). During the charging-discharging experiment, the MFC with a capacitance bioanode has a higher average peak current density of 5.06 mA cm-2 and 36 times larger than that with the bare bioanode. With the capacitive electrode, it is possible to let the MFC at the same time for production and storage of renewable electricity. Then two different operations (intermittent operation and continuous operation) of the MFC with a capacitive bioanode were studied to degrade Cr (VI) in cathode chamber. Results showed that the Cr (VI) removal rates of intermittent operation are much higher than that of continuous operation under the same time in the closed circuit state. This is due to the good ability of storing and releasing electron of the biological capacitor with MnO2 modified material. And this study showed that MFC with a capacitive bioanode is better adapted to treat heavy metal pollutants by intermittent mode. PMID- 27557904 TI - Out of pocket expenditure to deliver at public health facilities in India: a cross sectional analysis. AB - BACKGROUND: To expand access to safe deliveries, some developing countries have initiated demand-side financing schemes promoting institutional delivery. In the context of conditional cash incentive scheme and free maternity care in public health facilities in India, studies have highlighted high out of pocket expenditure (OOPE) of Indian families for delivery and maternity care. In this context the study assesses the components of OOPE that women incurred while accessing maternity care in public health facilities in Uttar Pradesh, India. It also assesses the determinants of OOPE and the level of maternal satisfaction while accessing care from these facilities. METHOD: It is a cross-sectional analysis of 558 recently delivered women who have delivered at four public health facilities in Uttar Pradesh, India. All OOPE related information was collected through interviews using structured pre-tested questionnaires. Frequencies, Mann Whitney test and categorical regression were used for data reduction. RESULTS: The analysis showed that the median OOPE was INR 700 (US$ 11.48) which varied between INR 680 (US$ 11.15) for normal delivery and INR 970 (US$ 15.9) for complicated cases. Tips for getting services (consisting of gifts and tips for services) with a median value of INR 320 (US$ 5.25) contributed to the major share in OOPE. Women from households with income more than INR 4000 (US$ 65.57) per month, general castes, primi-gravida, complicated delivery and those not accompanied by community health workers incurred higher OOPE. The significant predictors for high OOPE were caste (General Vs. OBC, SC/ST), type of delivery (Complicated Vs. Normal), and presence of ASHA (No Vs. Yes). OOPE while accessing care for delivery was one among the least satisfactory items and 76 % women expressed their dissatisfaction. CONCLUSION: Even though services at the public health facilities in India are supposed to be provided free of cost, it is actually not free, and the women in this study paid almost half of their mandated cash incentives to obtain delivery care. PMID- 27557906 TI - The fifteenth International Conference on Progress in Vaccination against Cancer (PIVAC-15), 6-8 October 2015, Tubingen, Germany: looking back on 15 years of progress. PMID- 27557905 TI - The Cognitive Profile of Ethosuximide in Children. AB - INTRODUCTION: Although ethosuximide is one of the oldest antiepileptic drugs (AEDs), little information is available about the cognitive side effects of ethosuximide. OBJECTIVE: The aim of this study was to investigate the cognitive profile of ethosuximide. METHODS: In this cross-sectional study, we used an extensive neuropsychological test battery in patients with epilepsy aged 6-16 years who were treated with monotherapy ethosuximide. We evaluated the efficacy of the drug by seizure frequency (seizure free or not). RESULTS: We included 61 patients with a mean age of 9.4 years [standard deviation (SD) 2.7] who used on average 686 mg/day (SD 245) ESM as monotherapy. ESM was effective in the majority of the patients (70 % were seizure free for at least 6 months at moment of inclusion). The total study population showed impairments of intelligence, visuomotor, and attentional function including activation/alertness. Comparisons between the well-controlled patients and patients who were not in remission showed significantly lower intelligence values and lower performance on the visual-perceptual and attentional tasks for the group with ongoing seizures. Our results suggested that the higher order cognitive dysfunctions (such as intelligence and visual-perceptual functions) may be regarded as seizure or aetiology effects and that the impaired fluid cognitive functions, such as activation/alertness, sustained auditory attention and attentional control or switching, were due to ESM. CONCLUSION: This study suggests the attentional dysfunction resulting in psychomotor slowing and alertness deficits may be regarded as effects of ethosuximide. Although no untreated baseline assessment was available, these effects are comparable to those of other AEDs, and ethosuximide may therefore be considered an AED with only mild effects on cognition. As ethosuximide is a first-line therapy for absence seizures in childhood, and drug-induced cognitive impairment may interfere with development, learning, and academic achievement, these findings are of interest to clinicians who prescribe this drug, especially when informing parents. PMID- 27557908 TI - Can we create a Canadian Perioperative Anesthesia Clinical Trials Group? We review the first five years and glimpse into the future. PMID- 27557909 TI - Factors that promote macrophage homing to adipose tissue in metabolic syndrome. AB - Metabolic syndrome (MetS), a common cardio-metabolic cluster, predisposes to both increased cardiovascular disease and diabetes. Both adipose tissue and monocyte/macrophages contribute to the increased inflammation in MetS. However there are sparse data on factors that determine macrophage recruitment into adipose tissue (AT). In this preliminary report in patients with MetS, without the confounding of diabetes and cardiovascular diseases, we show that plasma resistin, soluble CD14 and monocyte p38 MAP kinase activity correlate significantly with AT macrophage density and hence could be important biomediators of macrophage homing to AT in MetS. However larger studies are required to confirm these novel findings and elucidate other important factors. PMID- 27557910 TI - Vestibular Evoked Myogenic Potentials in Vestibular Migraine: Do They Help Differentiating From Meniere's Disease? AB - OBJECTIVE: To investigate whether both cervical and ocular vestibular myogenic potentials (cVEMPs and oVEMPs) to air-conducted sound (ACS) and bone-conducted vibration (BCV) can help to differentiate vestibular migraine (VM) and Meniere's disease (MD). STUDY DESIGN: Retrospective study. SETTINGS: A tertiary referral center. SUBJECTS AND METHODS: Twenty-eight patients with VM, 28 patients with definite unilateral MD, and 28 age-matched controls were included. Cervical VEMPs to 500 Hz ACS (cVEMPs-air) and 500 Hz BCV (cVEMPs-bone), oVEMPs to 500 Hz ACS (oVEMPs-air) and 500 Hz BCV (oVEMPs-bone), and caloric tests were performed. Results of these vestibular function tests were compared between the groups. RESULTS: The prevalence of abnormality was significantly higher in VM than in controls only for the caloric test (P < .05). Asymmetry ratios (ARs) for cVEMPs air and oVEMPs-air were significantly larger in VM than in controls (P < .05). Between VM and MD, the prevalence of abnormality was significantly different only for oVEMPs-air. The ARs for oVEMPs-air and caloric test asymmetries were significantly smaller in VM than in MD (P < .05). CONCLUSIONS: Among the vestibular function tests, oVEMPs-air may be most helpful for the differentiation of VM from MD as a group. PMID- 27557911 TI - Cochlear Implantation in Patients With CHARGE Syndrome. AB - OBJECTIVE: To determine the optimal surgical approach for cochlear implantation (CI) preoperatively based on the spatial relation of a displaced facial nerve (FN) and middle ear structures and to analyze clinical outcomes of CHARGE syndrome. METHODS: Facial nerve displacement and associated deviation of inner ear structures were analyzed in 13 patients (17 ears) with CHARGE syndrome who underwent CI. Surgical accessibility through the facial recess was assessed based on anatomical landmarks. Postoperative speech performance and associated clinical characteristics were analyzed. RESULTS: The most consistently identified ear anomalies were semicircular canal aplasia (100%), ossicular anomaly (100%), and vestibular hypoplasia (88%). Facial nerve displacement was found in 77% of cases (anteroinferior: 47%, anterior: 24%, inferior: 6%). The width of available surgical space around facial recess was significantly greater in cases of facial recess approach (2.85 +/- 0.9 mm) than those of alternative approach (0.12 +/- 0.29 mm, P = .02). Postoperatively, 53% achieved better than category 4 on the categories of auditory perception (CAP) scale. The CAP category was significantly correlated with internal auditory canal diameter (P = .025) and did not differ according to the applied surgical approach. CONCLUSION: Preoperative determination of surgical accessibility through facial recess would be useful for safe surgical approach, and successful hearing rehabilitation was achievable by applying appropriate surgical approaches. PMID- 27557912 TI - Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016. AB - The safe sedation of children for procedures requires a systematic approach that includes the following: no administration of sedating medication without the safety net of medical/dental supervision, careful presedation evaluation for underlying medical or surgical conditions that would place the child at increased risk from sedating medications, appropriate fasting for elective procedures and a balance between the depth of sedation and risk for those who are unable to fast because of the urgent nature of the procedure, a focused airway examination for large (kissing) tonsils or anatomic airway abnormalities that might increase the potential for airway obstruction, a clear understanding of the medication's pharmacokinetic and pharmacodynamic effects and drug interactions, appropriate training and skills in airway management to allow rescue of the patient, age- and size-appropriate equipment for airway management and venous access, appropriate medications and reversal agents, sufficient numbers of staff to both carry out the procedure and monitor the patient, appropriate physiologic monitoring during and after the procedure, a properly equipped and staffed recovery area, recovery to the presedation level of consciousness before discharge from medical/dental supervision, and appropriate discharge instructions. This report was developed through a collaborative effort of the American Academy of Pediatrics and the American Academy of Pediatric Dentistry to offer pediatric providers updated information and guidance in delivering safe sedation to children. PMID- 27557913 TI - Qualitative and Quantitative Effect of a Protective Chlorhexidine Varnish Layer Over Resin-infiltrated Proximal Carious Lesions in Primary Teeth. AB - PURPOSE: The purpose of this study was to assess the progression of noncavitated initial proximal carious lesions in primary teeth, infiltrated with low viscosity resins, both with and without an overlying layer of chlorhexidine varnish. METHODS: Forty-five children, with at least two white spot lesions on the proximal surfaces of primary molars, were assessed. The clinical procedure of resin infiltration (DMG, ICON) was similar in both groups. In the test group, after infiltration a double layer of chlorhexidine varnish (Cervitec Plus) was coated on the surface. Participants were recalled after nine months. Radiographic assessment was performed with GIMP software using representative histograms of the lesion. McNemar and chi-square tests were used to measure clinical and radiographic scores within and between groups. A two-sided (alpha equals two) P value less than 0.05 (P<=0.05) was considered statistically significant. RESULTS: The carious lesion with an International Caries Detection and Assessment System (ICDAS) three score had a statistically significant shift of pixel count distribution to a higher grayscale range in the test compared to the control group. CONCLUSION: The statistically significant positive histogram changes in the test group suggest benefits of an overlying chlorhexidine varnish layer on resin infiltration only when the carious surface had microcavitations. PMID- 27557914 TI - Improving Quality in Dentistry: An Imperative for the Profession. PMID- 27557915 TI - Letter to the Editor. PMID- 27557916 TI - Sealants for Preventing and Arresting Pit-and-fissure Occlusal Caries in Primary and Permanent Molars. AB - BACKGROUND: National Health and Nutrition Examination Survey 2011-2012 data indicated that, in the United States, nearly onefourth of children and over one half of adolescents experienced dental caries in their permanent teeth. The purpose of this review was to summarize the available clinical evidence regarding the effect of dental sealants for the prevention and management of pit-and fissure occlusal carious lesions in primary and permanent molars, compared with a control without sealants, with fluoride varnishes, or with other head-to head comparisons. TYPE OF STUDIES REVIEWED: The authors included parallel and split mouth randomized controlled trials that included at least 2 years of follow-up, which they identified using MEDLINE (via PubMed), Embase, LILACS, the Cochrane Central Register of Controlled Trials, and registers of ongoing trials. Pairs of reviewers independently conducted the selection of studies, data extraction, risk of bias assessments, and quality of the evidence assessments by using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Of 2,869 records screened, the authors determined that 24 articles (representing 23 studies) proved eligible. Moderate-quality evidence suggested that participants who received sealants had a reduced risk of developing carious lesions in occlusal surfaces of permanent molars compared with those who did not receive sealants (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.08-0.27) after 7 or more years of follow-up. When the authors compared studies whose investigators had compared sealants with fluoride varnishes, they found that sealants reduced the incidence of carious lesions after 7 or more years of follow-up (OR, 0.19; 95% CI, 0.07-0.51); however, this finding was supported by low-quality evidence. On the basis of the evidence, the authors could not provide a hierarchy of effectiveness among the studies whose investigators had conducted head-to-head comparisons. The investigators of 2 trials provided information about adverse events, but they did not report any adverse events. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Available evidence suggests that sealants are effective and safe to prevent or arrest the progression of noncavitated carious lesions compared with a control without sealants or fluoride varnishes. Further research is needed to provide information about the relative merits of the different types of sealant materials. PMID- 27557917 TI - Preparing the Pediatric Dentist for Palliative and End-of-life Care. AB - Pediatric dentists are the primary providers of dental homes for children with life-threatening and complex chronic conditions. These children are increasingly living at home and seeking health care in community-based settings, including dental offices. Pediatric dentists may feel ill prepared to assume the roles and responsibilities of a pediatric palliative care provider due to limited education and training during dental school and residency; however, they should be sensitive to the palliative care needs of children and families. The purpose of this clinical article was to highlight palliative care scenarios in pediatric dentistry and provide actionable resources to empower pediatric dentists to gather health care information, make informed ethical decisions, promote patient- and family-centered care, and prepare dentists and their dental teams for episodes of death and bereavement when providing a dental home to patients with life-threatening and complex chronic conditions. PMID- 27557918 TI - Effect of Tooth Mousse on Streptococcus Mutans in the Plaque of High Caries-risk Preschool Children: A Triple-Blind, Randomized Clinical Trial. AB - PURPOSE: Control of Streptococcus mutans can prevent caries in high-risk preschool children. The purpose of this study was to assess the effect of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) on Streptococcus mutans in the plaque of high-risk preschool children. METHODS: A triple blind, randomized, controlled clinical trial included 40 healthy three- to five-year-olds with at least one white spot lesion. They were randomized into test (daily applications of GC Tooth Mousse:CPP-ACP) and control groups (placebo mousse). Both groups received health education. Plaque samples were collected at baseline and after 15 days and cultured on Mitis Salivarius Agar. Percent reduction in S mutans count was calculated and compared between groups using t-test. RESULTS: Percent reduction of S mutans in the test group was slightly higher than in the control group (59 percent and 52 percent) but not significantly different after 15 days (P=0.27), with both groups showing a significant reduction from baseline (P<0.0001). CONCLUSIONS: Casein phosphopeptide amorphous calcium phosphate reduced Streptococcus mutans in the plaque of preschool children with noncavitated lesions after two weeks of daily application compared to baseline. It was not, however, significantly different from the reduction occurring after only a single session of health education. PMID- 27557919 TI - Caries, Toothbrushing Habits, and Fluoride Intake From Toothpaste by Brazilian Children According to Socioeconomic Status. AB - PURPOSE: The purpose of this study was to evaluate the prevalence of dental caries, toothbrushing habits, fluoride intake, and factors associated with the use of toothpaste in Brazilian children according to socioeconomic status (SES). METHODS: A cross-sectional observational study was conducted with 148 three- to four-year-olds of both low and high socioeconomic status. Data collection consisted of administering a questionnaire to guardians, brushing to determine fluoride intake, and examining the children's teeth to evaluate dental caries. RESULTS: In this study, 42 percent of children from high SES and 2.7 percent of children from low SES used toothpaste without fluoride or with a concentration below 1,000 ppm F. Fluoride intake was associated with SES, frequency of brushing, the amount of toothpaste used, and the concentration of fluoride present in toothpastes (P<0.05). Low SES children had a higher fluoride intake during brushing (0.045 mg F/kg body weight/day), compared to high SES children (0.023 mg F/kg body weight/day). Unlike low SES children (68.9 percent), all high SES children were caries free. CONCLUSIONS: A lower socioeconomic status was associated with a higher prevalence of dental caries and a higher intake of fluoride from toothpaste. PMID- 27557920 TI - Utilization of Chinese Herbal Medicine for Selected Oral Conditions in Two Pediatric Populations. AB - PURPOSE: To characterize traditional Chinese medicine (TCM) use, emphasizing herbal remedies, for oral conditions among two Chinese pediatric populations in the United States. METHODS: 318 unique ethnic Chinese parental units in Houston and Boston with children younger than 12 years old were interviewed for themselves and their children. Questionnaire included age, gender, duration in the United States, frequency of TCM use, and the five selected oral conditions for which TCM agents might be used. RESULTS: Parents (45.6 percent) and children (19.1 percent) used TCM for oral conditions, most commonly for aphthous ulcers (64.2 percent). Most commonly used TCM agents included watermelon frost (37.4 percent), niuhuang jiedu pian (15.5 percent), and honey/propolis (9.9 percent). Chi-square tests with logistic regression (P<0.05) showed duration of U.S. residency significantly affected (P=0.002), parental TCM usage, age group (P=0.003), and birth location (P=0.02) related to child use. Parental TCM use increased child likelihood of use (P<0.0001). CONCLUSIONS: In this study, traditional Chinese medicine was widely used for oral conditions by Chinese immigrants. Factors such as duration of U.S. residency, age, birth location, and parental use affect utilization of TCM in this population. Future studies are needed to explore the therapeutic properties of the various components of TCM. PMID- 27557921 TI - Success Rate of Treatments Provided for Early Childhood Caries under General Anesthesia: A Retrospective Cohort Study. AB - PURPOSE: The purpose of this study was to assess the success rate of various treatments provided under general anesthesia for early childhood caries (ECC) over three-year follow-up period. METHODS: ECC children no older than 72 months at the time of dental surgery, who had completed a three-year follow-up, were included. The success rate of every treatment was evaluated. The longevity of each treatment and significant factors associated with failures were assessed. RESULTS: A total of 818 children (55.8 percent were males with a mean age of 46.2+/-13.4 months old) were included. Of these, 32.9 percent had restored teeth that required further treatment during the three-year follow-up. Amalgam restorations and stainless steel crowns (SSCs) showed significantly longer survival than composite restorations in all types of restorations (P<.05). The survival rate of both indirect pulp capping and pulpotomies were the same (P=0.234), and they were significantly higher than that for pulpectomies (P=0.001, P=0.039, respectively). The lower lingual holding arch (LLHA) had a significantly lower survival rate than other space maintainers (P<0.05). CONCLUSIONS: SSCs and amalgam restorations were clinically more successful and had better survival times than composite restorations. The survival rate for the LLHA was low compared to other space maintainers. PMID- 27557922 TI - Very High Salivary Streptococcus Mutans Predicts Caries Progression in Young Children. AB - PURPOSE: Culturing mutans streptococci (MS) from children's saliva has high utility in caries risk assessment. The purpose of this retrospective cohort study was to examine its ability in predicting caries progression and determine sensitivity, specificity, and likelihood ratios of a very high ["too numerous to count (TNTC) MS test result. METHODS: 200 preschoolers (3.3+/-1.2 years, 50 percent no recoverable MS, 50 percent TNTC MS at first dental visit) were followed for five or more years. Caries experience of both groups was compared to identify predictors of caries presence and its progression. RESULTS: Controlling for demographic, oral health, and dental visit factors, TNTC preschoolers had both greater presence and extent of caries at the first dental visit (adjusted odds ratio [aOR] 8.0, 95 percent confidence interval [CI] 2.5 to 25.5) and caries progression at five or more years (aOR 6.0, 95 percent CI 2.4 to 15.0). Fewer TNTC preschoolers remained caries free over five years or longer (13 percent versus 77 percent for no MS). Overall, sensitivities and specificities exceeded 75 percent. CONCLUSIONS: Despite engagement in preventive dental care, children with TNTC MS were six times more likely to experience cavity increments than preschoolers with no recoverable MS at first visit. PMID- 27557923 TI - Structure and antitumor activity of the extracellular polysaccharides from Aspergillus aculeatus via apoptosis and cell cycle arrest. AB - Two extracellular polysaccharides, designated as WPA and WPB, were isolated from the fungus Aspergillus aculeatus using Q-Sepharose fast flow and Sephacryl S-300 column chromatography. WPA composed of mannose and galactose in a molar ratio of 3.9:1.0, and WPB mainly contained mannose. The molecular weight of WPA and WPB was about 28.1 kDa and 21.0 kDa, respectively. On the basis of methylation and NMR analysis, the possible main chain of WPA was [->5)-beta-D-Galf-(1 -> 2,6) alpha-D-Manp(1->], and WPB was mainly [->2,6)-alpha-D-Manp(1->], both with [alpha D-Manp(1 -> 2)-alpha-D-Manp(1 -> 2)-alpha-D-Manp(1->] substituted at C-2 of [ >2,6)-alpha-D-Manp(1->]. Meanwhile, WPA displayed a stronger anti-proliferative effect than WPB on HeLa, MCF-7 and MGC-803 cells in vitro. WPA and WPB could arrest HeLa cells in G2/M phase and induce HeLa cells apoptosis. Thus, our study provides evidence that WPA and WPB may be taken as potential candidates for treating cervical carcinoma. PMID- 27557926 TI - Asking Numbers to Speak: Verbal Markers and Stages of Change. AB - Through routine screenings for sexually transmitted infections (STIs) and HIV, medical providers are able to motivate behavior change. Although established models rely on quantitative measures, doing so requires time and ability to score each. Listening for verbal cues, however, could simplify the process of suggesting HIV screenings. Using mixed methods to identify verbal indicators for readiness to change, this article conducted two phases of study. First using quantitative means of identifying participant's knowledge of HIV, perceptions of safer sex, and readiness to change safer sex behaviors (N = 487). Interviews were then conducted exploring the possibility of verbal markers for one's readiness to change (n = 25). Results confirmed the use of verbal markers when discussing perceptions of risk. Identification of verbal markers, at three stages of change, provides new possibilities for medical providers' such as providing time saving and effective tools when seeking to motivate HIV and STI testing, and other safer sex behaviors. PMID- 27557924 TI - Timing Is Everything: Exploring Parental Decisions to Delay HPV Vaccination. AB - The delayed uptake of the human papillomavirus (HPV) vaccine offers an opportunity to explore how temporality and risk are at work in everyday life. Drawing from a mixed-methods study with parents ( N = 50) in Northern California, this study explored parents' decision to delay HPV vaccination for their children among parents who had not yet vaccinated ( n = 27). At the core of these decisions were temporal assessments of risk whereby parents weighed their child's (perceived) present risk of HPV exposure against the uncertain perceived risks of the vaccine itself. Our findings are promising as they indicate that given time, and the continued growth of evidence regarding the safety and effectiveness of HPV vaccination, completion rates should increase. However, our results also suggest that vaccination delays are not merely a matter of scientific doubt but also based on parents' (potentially inaccurate) perceptions of their child's sexual readiness, and thus potentially more difficult to overcome. PMID- 27557925 TI - Best Practice in Provider/Parent Interaction. AB - In this 3-year prospective grounded theory study in three pediatric settings, we aimed to develop a conceptualization of best practice health care providers (BPHCPs) in interaction with parents of children with complex, chronic, life threatening conditions. Analysis of semistructured interviews with 34 parents and 80 health care professionals (HCPs) and 88 observation periods of HCP/parent interactions indicated that BPHCPs shared a broad worldview; values of equity, family-centered care, and integrity; and a commitment to authentic engagement. BPHCPs engaged in direct care activities, in connecting behaviors, and in exquisitely attuning to particularities of the situation in the moment, resulting in positive outcomes for parents and HCPs. By focusing on what HCPs do well, findings showed that not only is it possible for HCPs to practice in this way, but those who do so are also recognized as being the best at what they do. We provide recommendations for practice and initial and ongoing professional education. PMID- 27557927 TI - Navigating the Decision Space: Shared Medical Decision Making as Distributed Cognition. AB - Despite increasing prominence, little is known about the cognitive processes underlying shared decision making. To investigate these processes, we conceptualize shared decision making as a form of distributed cognition. We introduce a Decision Space Model to identify physical and social influences on decision making. Using field observations and interviews, we demonstrate that patients and physicians in both acute and chronic care consider these influences when identifying the need for a decision, searching for decision parameters, making actionable decisions Based on the distribution of access to information and actions, we then identify four related patterns: physician dominated; physician-defined, patient-made; patient-defined, physician-made; and patient dominated decisions. Results suggests that (a) decision making is necessarily distributed between physicians and patients, (b) differential access to information and action over time requires participants to transform a distributed task into a shared decision, and (c) adverse outcomes may result from failures to integrate physician and patient reasoning. Our analysis unifies disparate findings in the medical decision-making literature and has implications for improving care and medical training. PMID- 27557929 TI - Some considerations for future research into the risks of radiation-induced cardiovascular diseases. PMID- 27557928 TI - Muslim immigrant women's views on cervical cancer screening and HPV self-sampling in Ontario, Canada. AB - BACKGROUND: Canada has observed significant decreases in incidence and mortality of cervical cancer in recent decades, and this has been attributed to appropriate screening (i.e., the Pap test). However, certain subgroups including Muslim immigrants show higher rates of cervical cancer mortality despite their lower incidence. Low levels of screening have been attributed to such barriers as lack of a family physician, inconvenient clinic hours, having a male physician, and cultural barriers (e.g., modesty, language). HPV self -sampling helps to alleviate many of these barriers. However, little is known about the acceptability of this evidence-based strategy among Muslim women. This study explored Muslim immigrant women's views on cervical cancer screening and the acceptability of HPV self-sampling. METHODS: An exploratory community-based mixed methods design was used. A convenience sample of 30 women was recruited over a 3 month period (June-August 2015) in the Greater Toronto Area. All were between 21 and 69 years old, foreign-born, self-identified as Muslim, and had good knowledge of English. Data were collected through focus groups. RESULTS: This study provides critical insights about the importance of religious and cultural beliefs in shaping the daily and health care experiences of Muslim women and their cancer screening decisions. Our study showed the deterring impact of beliefs and health practices in home countries on Muslim immigrant women's utilization of screening services. Limited knowledge about cervical cancer and screening guidelines and need for provision of culturally appropriate sexual health information were emphasized. The results revealed that HPV self-sampling provides a favorable alternative model of care to the traditional provider-administered Pap testing for this population. CONCLUSION: To enhance Muslim immigrant women screening uptake, efforts should made to increase 1) their knowledge of the Canadian health care system and preventive services at the time of entry to Canada, and 2) access to culturally sensitive education programs, female health professionals, and alternative modes of screening like HPV self-sampling. Health professionals need to take an active role in offering screening during health encounters, be educated about sexual health communication with minority women, and be aware of the detrimental impact of preconceived assumptions about sexual activity of Muslim women. PMID- 27557930 TI - Risk factors and outcomes of fetal macrosomia in a tertiary centre in Tanzania: a case-control study. AB - BACKGROUND: Fetal macrosomia is defined as birth weight >=4000 g. Several risk factors have been shown to be associated with fetal macrosomia. There has been an increased incidence of macrosomic babies delivered and the antecedent complications. This study assessed the risk factors, maternal and neonatal complications of fetal macrosomia in comparison with normal birth weight neonates. METHODS: A case-control study was conducted at the Muhimbili National Hospital (MNH) maternity and neonatal wards. Cases comprised of neonates with birth weight >=4000 g; controls were matched for sex and included neonates weighing 2500-3999 g. Detailed clinical and demographic information and laboratory investigations which included blood glucose, hematocrit and plasma calcium were collected. The child was followed up to discharge/death. RESULTS: The prevalence of macrosomic babies was 2.3 % (103 out of 4528 deliveries). Mean birth weight of macrosomic babies was 4.2 +/- 0.31 kg whereas in the controls it was 3.2 +/- 0.35 kg. Maternal weight >=80 kg, maternal age ranging between 30 and 39 years, multiparity, presence of diabetes mellitus, and gestational age >=40 years, previous history of fetal macrosomia and delivery weight >=80 kg were significantly associated with fetal macrosomia. Macrosomic infants were more likely to have birth asphyxia, shoulder dystocia, hypoglycemia, respiratory distress and perinatal trauma and increased risk of death compared to controls. Maternal complications such as postpartum hemorrhage, second degree perineal tears and prolonged labor occurred more frequently in the macrosomia group compared to controls (p-value <0.05), while shoulder dystocia, uterine rupture and maternal death were recorded only among the cases and none occurred in the controls. CONCLUSION: Fetal macrosomia was an important cause of maternal and neonatal morbidity at Muhimbili National Hospital. Presence of risk factors should alert the obstetrician to closely monitor these pregnancies and plan on appropriate mode of delivery. Macrosomic neonates should be routinely screened and appropriately managed for hypoglycemia. PMID- 27557931 TI - Burden of malaria is higher among children in an internal displacement camp compared to a neighbouring village in the Democratic Republic of the Congo. AB - BACKGROUND: In the Democratic Republic of the Congo (DRC), violent conflict has caused the displacement of millions of people into camps where they are exposed to poor living conditions and high rates of infectious diseases. Malaria, in particular, is a major cause of mortality in children under five; however, the burden of disease in displacement camps has not previously been described. METHODS: Two cross-sectional surveys were performed. First, prevalence of Plasmodium falciparum antigenemia was measured in a random sample of 200 children living in a displacement camp and 200 children from a nearby village (control group). Second, the proportion of febrile illness attributable to malaria was measured in a study of 100 children from the displacement camp and 100 children from the control village presenting to the same health clinic with fever. All participants were tested for P. falciparum with a rapid diagnostic test and additional demographic data, clinical characteristics, and malaria risk factors were determined using a parental questionnaire. RESULTS: In the community survey, children living in the displacement camp had a higher prevalence of P. falciparum infection (17 %) than controls (7.5 %) (OR 2.6; 95 % CI 1.3-4.1; P = 0.0095). In the clinic-based survey, the proportion of febrile illness attributable to malaria was higher among children from the displacement camp (78 %) than controls (39 %) (OR 5.5; 95 % CI 3.0-10.3; P < 0.001). Household bed net ownership and use was significantly lower in the displacement camp than control village in both surveys. Statistically significant differences in household wealth, maternal education, and exposure to community violence were also found. CONCLUSIONS: Population displacement due to violent conflict appears to be a risk factor for malaria, a major cause of child mortality. Children living in displacement camps are a relatively understudied population, but have a high burden of malaria, despite control programmes focused on bed net distribution. PMID- 27557932 TI - The emerging role of estrogen in B cell malignancies. AB - Increasing evidence implicates a role of estrogens in hematological malignancies. We reviewed current knowledge on the emerging role of estrogens and estrogen receptors in normal B-cell function, chronic lymphocytic leukemia, and B-cell lymphoma. Data support that (1) normal human peripheral blood cells (mononuclear cells, total lymphocytes, T as well as B lymphocytes, and NK cells) express both estrogen receptor subtypes (ERalpha and ERbeta), (2) B-cell malignancies express mainly ERbeta while selective ERbeta agonists inhibit cell growth and induce apoptosis, (3) estrogens regulate, via an ER-mediated pathway, gene expression of cyclins, kinases, bcl-2 proto-oncogene, activation-induced deaminase (AID), and transcription factors, associated with changes in BCR signaling and B cell tumorigenesis. In conclusion, estrogen receptors play an important role in normal B-cell function and B-cell tumorigenesis; however, further investigations are required to delineate the role of estrogens and estrogen receptors in the etiopathogenesis and therapy of B-cell malignancies. PMID- 27557933 TI - Childhood maltreatment as a risk factor for diabetes: findings from a population based survey of Canadian adults. AB - BACKGROUND: It is well established that childhood maltreatment (CM) is a risk factor for various mental and substance use disorders. To date, however, little research has focused on the possible long-term physical consequences of CM. Diabetes is a chronic disease, for which an association with CM has been postulated. METHODS: Based on data from a sample of 21,878 men and women from the 2012 Canadian Community Health Survey - Mental Health (CCHS - MH), this study examines associations between three types of CM (childhood physical abuse (CPA), childhood sexual abuse (CSA), and childhood exposure to intimate partner violence (CEIPV)) and diabetes in adulthood. Multiple logistic regression models were used to examine associations between CM and diabetes controlling for the effects of socio-demographic characteristics and risk factors for type 2 diabetes. RESULTS: When controlling socio-demographic characteristics, diabetes was significantly associated with reports of severe and frequent CPA (OR = 1.8) and severe and frequent CSA (OR = 2.2). A dose-response relationship was observed when co occurrence of CSA and CPA was considered with the strongest association with diabetes being observed when both severe and frequent CSA and CPA were reported (OR = 2.6). Controlling for type 2 diabetes risk factors attenuated associations particularly for CPA. CEIPV was not significantly associated with having diabetes in adulthood. CONCLUSION: CPA and CSA are risk factors for diabetes. For the most part, associations between CPA and diabetes are mediated via risk factors for type 2 diabetes. Failure to consider severity and frequency of abuse may limit our understanding of the importance of CM as a risk factor for diabetes. PMID- 27557935 TI - Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7. AB - OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense. PMID- 27557934 TI - The last phase of life with dementia in Swiss nursing homes: the study protocol of the longitudinal and prospective ZULIDAD study. AB - BACKGROUND: The proportion of older people with advanced dementia who will die in nursing homes is constantly growing. However, little is known about the dying phase, the type of symptoms, the management of symptoms and the quality of life and dying in people with advanced dementia. The ZULIDAD (Zurich Life and Death with Advanced Dementia) study aims at extending the current scientific knowledge by providing first data from Switzerland. METHODS: The ZULIDAD study employs a prospective design to study nursing home residents with advanced dementia for three years or until their death in eleven nursing homes in Zurich. Observational data from quarterly questionnaires for relatives and primary nurses is combined with data from the Resident Assessment Instrument - Minimum Data Set (RAI-MDS). Special focus is put on 1) the cross-sectional analysis of baseline and post mortem data regarding quality of life and quality of dying and how the perceptions of these measures differ between relatives and primary nurses, 2) the longitudinal analyses of established health outcome measures (e.g., EOLD, MSSE, BISAD, QUALID) in order to understand their trajectories and 3) international comparisons of cross-sectional and longitudinal data. DISCUSSION: The ZULIDAD study is one of the few existing prospective studies on end-of-life care in dementia and it is the first prospective study to describe the situation in Switzerland. Its multi-perspective approach allows a comprehensive approximation to central health outcome measures at the end of life such as pain, suffering or quality of life. Providing insights into the current provision of care, it can serve as a basis for improving dementia end-of-life care in Switzerland and internationally. PMID- 27557936 TI - Erratum: Tsunami-generated magnetic fields may constrain focal mechanisms of earthquakes. PMID- 27557937 TI - Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers. AB - Ferric pyrophosphate citrate (Triferic) is a water-soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double-blind, randomized, placebo-controlled, single , ascending-dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron-replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFetot ), transferrin-bound iron (TBI), hepcidin-25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFetot was observed in placebo-treated subjects. Concentrations of sFetot and TBI increased rapidly after drug administration, with maximum serum concentrations (Cmax ) reached at the end of infusion. Increases in baseline-corrected Cmax and area under the concentration-time curve from 0 to the time of the last quantifiable concentration (AUC0-t ) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half life 1.2-2 hours). No significant changes from baseline in serum hepcidin-25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation. PMID- 27557938 TI - MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data. AB - Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using next-generation sequencing remains challenging. We develop MuSE ( http://bioinformatics.mdanderson.org/main/MuSE ), Mutation calling using a Markov Substitution model for Evolution, a novel approach for modeling the evolution of the allelic composition of the tumor and normal tissue at each reference base. MuSE adopts a sample-specific error model that reflects the underlying tumor heterogeneity to greatly improve the overall accuracy. We demonstrate the accuracy of MuSE in calling subclonal mutations in the context of large-scale tumor sequencing projects using whole exome and whole genome sequencing. PMID- 27557939 TI - The Potential of Flavonolignans in Prostate Cancer Management. AB - BACKGROUND: The generic name "flavonolignan" was created in 1968 for a relatively small class of naturally occurring hybrid molecules biogenetically originated from ubiquitous flavonoids and lignans (phenylpropanoids). The first group of flavonolignans was extracted from Silybum marianum that has long been used for hepatoprotection. Recently, the medicinal merit of flavonolignans has been extended to the prostate cancer management. METHODS: Systematic interpretation and summarization of the relevant literature. RESULTS: Over forty naturally occurring flavonolignans have so far been obtained from various plants. Certain flavonolignans have been demonstrated by in vitro cell-based and in vivo animal based experiments, and human clinical studies i) to possess effective chemopreventive function against various tumor promoters; ii) to show the anti angiogenic efficacy; iii) to have potential in treating prostate cancer; iv) to sensitize prostate tumors to chemotherapeutic agents through down-regulation of P glycoprotein and other mechanisms; and v) to be used by prostate cancer patients to protect or treat the hepatotoxicity caused by several chemotherapies. Certain flavonolignans can synergize with well-established chemotherapeutic agents for prostate cancer. CONCLUSION: This review provides a systematic and in-depth overview of the promise and potential of flavonolignans in prostate cancer management, which covers their chemopreventive effect, chemotherapeutic treatment, mechanisms of actions, synthetic derivatives, structure-activity relationships, and the difference in inhibiting prostate cancer cell proliferation between certain flavonoligans and their respective flavonoid counterpart. This summarization aims to provide valuable insights into further and rational development of flavonolignans for prostate cancer management by interpreting the data reported in the literature. PMID- 27557942 TI - Impact of non-contrast enhanced volumetric MRI-based feeder localization in the treatment of spinal dural arteriovenous fistula. AB - BACKGROUND: The preoperative localization of the feeder of spinal dural arteriovenous fistula (SDAVF) could simplify the diagnostic spinal angiographic procedure. Localization by non-contrast-enhanced MRI-based techniques is an attractive option. However, the usefulness of such an approach for evaluation of SDAVF has not yet been reported. OBJECTIVE: To study the impact of non-contrast MRI-based feeder localization, followed by targeted spinal angiography, in the evaluation of SDAVF before endovascular intervention. MATERIALS AND METHODS: Prospectively collected data were analyzed and the level of the feeder was localized preoperatively. The procedural time for targeted spinal angiography was calculated and compared with that of a historical cohort, who underwent routine spinal angiographic examination before the study period. Follow-up MRI was carried out to assess the reliability of this model for detection of occasional metachronous lesions that might be missed with this approach. RESULTS: Seven patients underwent targeted spinal angiography during the study. The feeder level was accurately identified in five patients and was localized to one vertebral level in six patients. The correlation between MRI and DSA was statistically significant. The number of spinal levels assessed was fewer and overall procedure time was significantly shorter compared to historical cohort (58 min vs 162 min, respectively; p<0.001). Intervention was coupled with targeted angiography in two patients. Follow-up MRI demonstrated flow voids in one patient, who had recurrent fistula at one vertebral level below the previously embolized feeder. CONCLUSIONS: The non-contrast MRI-based localization technique can reliably detect the level of feeder and help in therapeutic planning of SDAVF. The localization techniques potentially shorten the angiographic procedure and may facilitate simultaneous endovascular definitive treatment. Inclusion of follow-up MRI may be useful for detection of synchronous or metachronous lesions if a targeted approach is adopted. Additionally, this helps to identify failed endovascular therapy. PMID- 27557940 TI - Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biological features, although they may show some differences on cumulative yield, proliferative ability and differentiation potential. The standardization of MSCs growth and their functional amplification is a mandatory objective of cell therapies. The aim of this study was to evaluate the cumulative yield and the ex vivo amplification potential of MSCs obtained from various sources and different subjects, using defined culture conditions with a standardized platelet lysate (PL) as growth stimulus. METHODS: MSCs isolated from BM, UCT and AT and expanded in human PL were compared in terms of cumulative yield and growth potential per gram of starting tissue. MSCs morphology, phenotype, differentiation potential, and immunomodulatory properties were also investigated to evaluate their biological characteristics. RESULTS: The use of standardized PL-based culture conditions resulted in a very low variability of MSC growth. Our data showed that AT has the greater capacity to generate MSC per gram of initial tissue, compared to BM and UCT. However, UCT-MSCs replicated faster than AT-MSCs and BM-MSCs, revealing a greater proliferation capacity of this source irrespective of its lower MSC yield. All MSCs exhibited the typical MSC phenotype and the ability to differentiate into all mesodermal lineages, while BM-MSCs showed the most prominent immunosuppressive effect in vitro. CONCLUSIONS: The adoption of standardized culture conditions may help researchers and clinicians to reveal particular characteristics and inter-individual variability of MSCs sourced from different tissues. These data will be beneficial to set the standards for tissue collection and MSCs clinical-scale expansion both for cell banking and for cell based therapy settings. PMID- 27557943 TI - Rescue mechanical thrombectomy using a retrievable stent for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms. AB - OBJECTIVE: To examine the safety and efficacy of mechanical thrombectomy using a retrievable stent for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms. METHODS: Between June 2011 and June 2015, 631 consecutive patients with ruptured intracranial aneurysms underwent coil embolization at 6 hospitals. Among 53 patients who had thromboembolic complications, 15 patients harboring 15 aneurysms underwent rescue mechanical thrombectomy with a retrievable stent for the treatment of thromboembolic occlusion during the coiling of ruptured aneurysms. The patients' clinical and radiologic outcomes were retrospectively reviewed. RESULTS: Of the 15 aneurysms, coiling alone was used for 13 (86.7%), and stent-assisted coiling was performed for 2 (13.3%). Thromboembolic occlusion most frequently occurred distal to the aneurysm (n=10, 66.7%), followed by proximal to the aneurysm (n=3, 20%), and at the coil-parent vessel interface (n=2, 13.3%). All patients underwent mechanical thrombectomy with a retrievable stent, including 5 patients who were initially treated with an IA tirofiban infusion. Complete recanalization (Thrombolysis in Cerebral Infarction (TICI) 3) was obtained in 13 (86.7%) and partial recanalization (TICI 2b) in 2 (13.3%). Two patients who had received IA tirofiban before mechanical thrombectomy had hemorrhagic complications. At 6 months after discharge, 9 patients had a modified Rankin Scale (mRS) score of 1, 3 patients were mRS 2, 1 patient was mRS 3, 1 patient was mRS 4, and 1 patient was mRS 6. CONCLUSIONS: Rescue mechanical thrombectomy using a retrievable stent can be a useful treatment for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms. PMID- 27557944 TI - Endovascular treatment of complex intracranial aneurysms using Acandis Acclino stents. AB - OBJECTIVE: To determine the safety and effectiveness of a new low-profile, laser cut, closed-cell stent system in the treatment of complex intracranial aneurysms. METHODS: A total number of 43 patients with complex intracranial aneurysms were treated using 60 Acandis Acclino stent systems (follow-up 2012-2016; mean 11 months). 36 patients presented with wide-necked intracranial aneurysms, dissecting aneurysms were seen in 7 patients. 39 patients received stent-assisted coiling. We analyzed demographic data and follow-up results. RESULTS: Sixty stents were successfully deployed. In one paraophthalmic internal carotid artery aneurysm the stent could not be placed. Thirty-three wide necked aneurysms were treated by single or multiple stent-assisted coiling. Complete occlusion was achieved in 31 of those cases (94% Raymond-Roy occlusion classification, RROC 1). Two patients showed stable residual aneurysmal filling (RROC 3). In three wide necked aneurysms, sole stenting was the preferred treatment. For dual stent assisted procedures the kissing-Y stenting technique was successfully performed in 11 aneurysms. In all dissecting aneurysms constructive therapy with stenting and preservation of the affected parent artery was achieved. Additional subsequent coil embolization was intentionally planned and successfully performed in 6 of the 7 dissecting aneurysms. The overall directly procedure-related complication rate was 7%, including one death. CONCLUSIONS: Endovascular treatment of complex intracranial aneurysms using Acclino stents is a feasible and safe procedure with low complication rates. Even severe cases can be treated among others using the kissing-Y stenting technique, with good mid-term results. PMID- 27557945 TI - Cytoskeletal abnormalities and neutrophil dysfunction in WDR1 deficiency. AB - Cell motility, division, and structural integrity depend on dynamic remodeling of the cellular cytoskeleton, which is regulated in part by actin polymerization and depolymerization. In 3 families, we identified 4 children with recurrent infections and varying clinical manifestations including mild neutropenia, impaired wound healing, severe stomatitis with oral stenosis, and death. All patients studied had similar distinctive neutrophil herniation of the nuclear lobes and agranular regions within the cytosol. Chemotaxis and chemokinesis were markedly impaired, but staphylococcal killing was normal, and neutrophil oxidative burst was increased both basally and on stimulation. Neutrophil spreading on glass and cell polarization were also impaired. Neutrophil F-actin was elevated fourfold, suggesting an abnormality in F-actin regulation. Two dimensional differential in-gel electrophoresis identified abnormal actin interacting protein 1 (Aip1), encoded by WDR1, in patient samples. Biallelic mutations in WDR1 affecting distinct antiparallel beta-strands of Aip1 were identified in all patients. It has been previously reported that Aip1 regulates cofilin-mediated actin depolymerization, which is required for normal neutrophil function. Heterozygous mutations in clinically normal relatives confirmed that WDR1 deficiency is autosomal recessive. Allogeneic stem cell transplantation corrected the immunologic defect in 1 patient. Mutations in WDR1 affect neutrophil morphology, motility, and function, causing a novel primary immunodeficiency. PMID- 27557946 TI - Regulation of Vegf signaling by natural and synthetic ligands. AB - The mechanisms that allow cells to bypass anti-vascular endothelial growth factor A (VEGFA) therapy remain poorly understood. Here we use zebrafish to investigate this question and first show that vegfaa mutants display a severe vascular phenotype that can surprisingly be rescued to viability by vegfaa messenger RNA injections at the 1-cell stage. Using vegfaa mutants as an in vivo test tube, we found that zebrafish Vegfbb, Vegfd, and Pgfb can also rescue these animals to viability. Taking advantage of a new vegfr1 tyrosine kinase-deficient mutant, we determined that Pgfb rescues vegfaa mutants via Vegfr1. Altogether, these data reveal potential resistance routes against current anti-VEGFA therapies. In order to circumvent this resistance, we engineered and validated new dominant negative Vegfa molecules that by trapping Vegf family members can block vascular development. Thus, our results show that Vegfbb, Vegfd, and Pgfb can sustain vascular development in the absence of VegfA, and our newly engineered Vegf molecules expand the toolbox for basic research and antiangiogenic therapy. PMID- 27557947 TI - Medical encounters for opioid-related intoxications in Southern Nevada: sociodemographic and clinical correlates. AB - BACKGROUND: Despite today's heightened concern over opioid overdose, the lack of population-based data examining clinical and contextual factors associated with opioid use represents a knowledge gap with relevance to prevention and treatment interventions. We sought to quantify rates of emergency department (ED) visits and inpatient hospitalizations for harmful opioid effects and their sociodemographic differentials as well as clinical correlates in Southern Nevada, using ED visit and hospital inpatient discharge records from 2011 to 2013. METHODS: Cases were identified by ICD-9-CM diagnosis codes for opioid poisoning and opioid-type drug dependence and abuse as well as poisoning and adverse effect E-codes. Comorbid conditions, including pain-related diagnoses, major chronic diseases, affective disorders, sleep disorders, sexually transmitted infections and viral hepatitis were assessed from all available diagnosis fields. Counts by age-race per zip code were modeled by negative binomial regression. Opioid injuries were further examined as a function both of neighborhood income and individual characteristics, with mixed-effects logistic regression to estimate the likelihood for an adverse outcome. RESULTS: Opioid intoxications and comorbidities were more common in low-income communities. The multivariable adjusted rate for opioid-related healthcare utilization was 42 % higher in the poorest vs. richest quartile during the study period. The inter-quartile (quartile 1 vs. 4) rate increases for chronic bodily pains (44 %), hypertension (89 %), renal failure/diabetes (2.6 times), chronic lower respiratory disease (2.2 times), and affective disorders (57 %) were statistically significant. Chronic disease comorbidity was greater among non-Hispanic blacks, whereas abuse/dependence related disorders, alcohol or benzodiazepine co-use, chronic bodily pains, and affective disorders were more prevalent among non-Hispanic whites than nonwhites. CONCLUSIONS: There were consistent patterns of disparities in healthcare utilization across sociodemographic groups for opioid-associated disorders. Further initiatives to evaluate the determinants of overdose and abuse and to implement targeted response efforts are needed. PMID- 27557948 TI - Non-excitable fluorescent protein orthologs found in ctenophores. AB - BACKGROUND: Fluorescent proteins are optically active proteins found across many clades in metazoans. A fluorescent protein was recently identified in a ctenophore, but this has been suggested to derive from a cnidarian, raising again the question of origins of this group of proteins. RESULTS: Through analysis of transcriptome data from 30 ctenophores, we identified a member of an orthologous group of proteins similar to fluorescent proteins in each of them, as well as in the genome of Mnemiopsis leidyi. These orthologs lack canonical residues involved in chromophore formation, suggesting another function. CONCLUSIONS: The phylogenetic position of the ctenophore protein family among fluorescent proteins suggests that this gene was present in the common ancestor of all ctenophores and that the fluorescent protein previously found in a ctenophore actually derives from a siphonophore. PMID- 27557950 TI - Neonatal domoic acid alters in vivo binding of [11C]yohimbine to alpha2 adrenoceptors in adult rat brain. AB - RATIONALE: Epilepsy is a debilitating seizure disorder that affects approximately 50 million people. Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset. OBJECTIVE: We investigated the role of alpha2-adrenoceptors in vivo in a neonatal domoic acid (DOM) rat model of epilepsy. METHODS: We injected male Sprague-Dawley rats daily from postnatal day 8-14 with saline or one of two sub-convulsive doses, 20 MUg/kg (DOM20) or 60 MUg/kg (DOM60) DOM, an AMPA/kainate receptor agonist. The rats were observed in open field, social interaction and forced swim tests at day 50, 75 and 98, respectively. At ~120 days of age, four rats per group were injected and scanned with [11C]yohimbine, an alpha2-adrenoceptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner to measure alpha2 adrenoceptor binding. RESULTS: DOM60-treated rats spent more time in the periphery during the open field test and had a significant 26-33 % reduction in [11C]yohimbine binding in the hypothalamus, hippocampus and orbital prefrontal cortex compared to saline-treated rats. On the other hand, DOM20 rats had a significant 34-40 % increase in [11C]yohimbine binding in the hypothalamus, amygdala and entorhinal cortex compared to saline-treated rats, with no obvious behavioural differences. CONCLUSIONS: The current data clearly indicate that low concentrations of DOM given to rats in their second week of life induces long term changes in alpha2-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype. PMID- 27557949 TI - Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study. AB - RATIONALE: Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial. OBJECTIVE: The objective of this study was to examine the relationship between antipsychotic related dopamine D2/3 receptor occupancy and negative symptoms in patients with schizophrenia. METHODS: Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [11C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose. RESULTS: No significant relationship was found between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship. CONCLUSIONS: Our cross sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined. PMID- 27557951 TI - Topological Structures and Membrane Nanostructures of Erythrocytes after Splenectomy in Hereditary Spherocytosis Patients via Atomic Force Microscopy. AB - Hereditary spherocytosis is an inherited red blood cell membrane disorder resulting from mutations of genes encoding erythrocyte membrane and cytoskeletal proteins. Few equipments can observe the structural characteristics of hereditary spherocytosis directly expect for atomic force microscopy In our study, we proved atomic force microscopy is a powerful and sensitive instrument to describe the characteristics of hereditary spherocytosis. Erythrocytes from hereditary spherocytosis patients were small spheroidal, lacking a well-organized lattice on the cell membrane, with smaller cell surface particles and had reduced valley to peak distance and average cell membrane roughness vs. those from healthy individuals. These observations indicated defects in the certain cell membrane structural proteins such as alpha- and beta-spectrin, ankyrin, etc. Until now, splenectomy is still the most effective treatment for symptoms relief for hereditary spherocytosis. In this study, we further solved the mysteries of membrane nanostructure changes of erythrocytes before and after splenectomy in hereditary spherocytosis by atomic force microscopy. After splenectomy, the cells were larger, but still spheroidal-shaped. The membrane ultrastructure was disorganized and characterized by a reduced surface particle size and lower than normal Ra values. These observations indicated that although splenectomy can effectively relieve the symptoms of hereditary spherocytosis, it has little effect on correction of cytoskeletal membrane defects of hereditary spherocytosis. We concluded that atomic force microscopy is a powerful tool to investigate the pathophysiological mechanisms of hereditary spherocytosis and to monitor treatment efficacy in clinical practices. To the best of our knowledge, this is the first report to study hereditary spherocytosis with atomic force microscopy and offers important mechanistic insight into the underlying role of splenectomy. PMID- 27557952 TI - Cross-modal integration of multimodal courtship signals in a wolf spider. AB - Cross-modal integration, i.e., cognitive binding of information transmitted in more than one signal mode, is important in animal communication, especially in complex, noisy environments in which signals of many individuals may overlap. Males of the brush-legged wolf spider Schizocosa ocreata (Hentz) use multimodal communication (visual and vibratory signals) in courtship. Because females may be courted by multiple males at the same time, they must evaluate co-occurring male signals originating from separate locations. Moreover, due to environmental complexity, individual components of male signals may be occluded, altering detection of sensory modes by females. We used digital multimodal playback to investigate the effect of spatial and temporal disparity of visual and vibratory components of male courtship signals on female mate choice. Females were presented with male courtship signals with components that varied in spatial location or temporal synchrony. Females responded to spatially disparate signal components separated by >=90 degrees as though they were separate sources, but responded to disparate signals separated by <=45 degrees as though they originated from a single source. Responses were seen as evidence for cross-modal integration. Temporal disparity (asynchrony) in signal modes also affected female receptivity. Females responded more to male signals when visual and vibratory modes were in synchrony than either out-of-synch or interleaved/alternated. These findings are consistent with those seen in both humans and other vertebrates and provide insight into how animals overcome communication challenges inherent in a complex environment. PMID- 27557953 TI - Quantification of the cellular dose and characterization of nanoparticle transport during in vitro testing. AB - BACKGROUND: The constant increase of the use of nanomaterials in consumer products is making increasingly urgent that standardized and reliable in vitro test methods for toxicity screening be made available to the scientific community. For this purpose, the determination of the cellular dose, i.e. the amount of nanomaterials effectively in contact with the cells is fundamental for a trustworthy determination of nanomaterial dose responses. This has often been overlooked in the literature making it difficult to undertake a comparison of datasets from different studies. Characterization of the mechanisms involved in nanomaterial transport and the determination of the cellular dose is essential for the development of predictive numerical models and reliable in vitro screening methods. RESULTS: This work aims to relate key physico-chemical properties of gold nanoparticles (NPs) to the kinetics of their deposition on the cellular monolayer. Firstly, an extensive characterization of NPs in complete culture cell medium was performed to determine the diameter and the apparent mass density of the formed NP-serum protein complexes. Subsequently, the kinetics of deposition were studied by UV-vis absorbance measurements in the presence or absence of cells. The fraction of NPs deposited on the cellular layer was found to be highly dependent on NP size and apparent density because these two parameters influence the NP transport. The NP deposition occurred in two phases: phase 1, which consists of cellular uptake driven by the NP-cell affinity, and phase 2 consisting mainly of NP deposition onto the cellular membrane. CONCLUSION: The fraction of deposited NPs is very different from the initial concentration applied in the in vitro assay, and is highly dependent of the size and density of the NPs, on the associated transport rate and on the exposure duration. This study shows that an accurate characterization is needed and suitable experimental conditions such as initial concentration of NPs and liquid height in the wells has to be considered since they strongly influence the cellular dose and the nature of interactions of NPs with the cells. PMID- 27557954 TI - Allografts supercharged with bone-marrow-derived mesenchymal stem cells possess equivalent osteogenic capacity to that of autograft: a study with long-term follow-ups of human biopsies. AB - PURPOSE: Bone-marrow-derived mesenchymal stem cells (BM-MSCs) have been proposed to enhance bone formation in allografts. However, it is not known whether a combination of MSCs, contained in bone marrow concentrate (BMC) and structural allograft could be better than an allograft without MSCs and equivalent to a femoral head autograft in terms of histologic bone formation and long-term cellularity in the graft. After ten years of follow-up, three types of grafts: those initially loaded with BM-MSCs; dead, irradiated allografts; autografts. MATERIALS AND METHODS: Twenty patients received acetabular grafting during hip surgery and subsequently underwent femoral hip revision eight to 13 years later (average 10 years). Revision surgery was for reasons other than graft failure. These 20 patients had received eight allografts initially loaded with BM-MSCs: six dead irradiated allografts and six autografts. The number of MSCs present in the three types of graft were evaluated at the time of initial surgery and at revision. New bone formation associated in the acetabular graft was assessed by histology and calculated as a percentage of total available bony area. RESULTS: At the most recent follow-ups (average 10 years), concentration of MSCs in allografts previously loaded with BM-MSCs was higher than that found in autografts. There were low or no MSCs found in uncharged allografts. New-bone formation analysis showed that allografts loaded with BM-MSCs produced more new bone (35 %; range 20-50 %) compared with either uncharged allografts (9 %; range 2-15 %) or autografts (24 %; range 12-32 %). CONCLUSIONS: Our observations with allografts charged with BM-MSCs provides evidence in support of a long-term benefit of supercharging bone allografts with autologous BM-MSCs. PMID- 27557955 TI - Effects of multi-site infiltration analgesia on pain management and early rehabilitation compared with femoral nerve or adductor canal block for patients undergoing total knee arthroplasty: a prospective randomized controlled trial. AB - PURPOSE: The aim of this study was to combine intra-articular and peri-articular with wound infiltration analgesia (multi-site infiltration analgesia, MIA) for patients undergoing total knee arthroplasty (TKA) and compare its pain management and early rehabilitation effect with the commonly used nerve block including adductor cannel block (FNB) and femoral nerve block (ACB). METHOD: We conducted a prospective randomized controlled trial and 77 patients were included for analysis. The patients were randomized over three groups. The first group (26 patients) received multi-site infiltration analgesia (MIA group), the second group (27 patients) received femoral nerve block (FNB group), and the third group (24 patients) received adductor cannel block (ACB group). RESULTS: MIA showed better pain control at rest during the first 12 hours (p < 0.05 respectively) and less opioid consumption after operation than the other two groups (p < 0.05, respectively), but ACB and FNB revealed similar outcomes (p > 0.05). At the same time, there are no significant differences in pain score with activity, vital signs, and occurrence of complication (p > 0.05, respectively) among the three groups. When evaluated the early rehabilitation, MIA and ACB had similar outcomes on post-operative muscle strength (p > 0.05), but they showed better quadriceps strength when compared FNB (p < 0.05). Although the knee ROM of the patients with FNB showed better results (p < 0.05), their ambulation ability was inferior to those in MIA group (p < 0.05 and ACB group (p < 0.05) early after the operation, besides, MIA patients were superior to ACB patients (p < 0.05). Furthermore, MIA spent less time on operation and post-operative hospital stays when compared with FNB and ACB (p < 0.05, respectively), while the ACB and FNB were without significant difference (p < 0.05, respectively). CONCLUSION: ACB was not inferior to FNB on pain control, but it was better on early mobilization. However, MIA that combine intra-articular and peri-articular with wound infiltration analgesia after TKA was more effective on pain control at rest, with better efficacy on early rehabilitation and easier to perform when compared with these commonly used nerve block. We recommended our MIA for pain relief and fast rehabilitation after TKA. PMID- 27557956 TI - Cervical corpectomies: results of a survey and review of the literature on diagnosis, indications, and surgical technique. AB - OBJECTIVES: Cervical corpectomy is an uncommon procedure and there are only limited data on the procedure's indications, surgical approaches, and complications. The diagnosis, indications, surgical planning, and complications of cervical corpectomy were therefore surveyed to clarify the treatment strategies used by spinal surgeons in central Europe, with special attention to preoperative planning and decision-making for additional dorsal approaches in multilevel cases. MATERIALS AND METHODS: An online survey with 18 questions on the preoperative, intraoperative, and postoperative management of cervical corpectomies was conducted. The relevant specialist societies in Germany and Austria provided 1137 contacts for surgeons, and the responses were compared with recent literature reports. RESULTS: In all, 302 surgeons (27 %) completed the survey, with wide variability in the treatment options offered. Most (51 %) perform fewer than five anterior cervical corpectomy and fusion (ACCF) procedures per year; 35 % do 5-20 per year. Anterior cervical discectomy and fusion (ACDF) was preferred by 41 % of the participants to laminoplasty/laminectomy (19 %/16 %) and ACCF (12 %). Most indications for ACCF involved degenerative (27 %), traumatic (17 %), and neoplastic (20 %) conditions. Intraoperative and postoperative complications were mainly associated with hardware failure. One third of the surgeons tend to use an additional dorsal approach to increase the corpectomy construct's stability for either two-level or three-level corpectomies. CONCLUSIONS: There is no current consensus in central Europe on the treatment of complex cervical disease and cervical corpectomy. The procedure is still rare, and the need for additional dorsal fixation is unclear. Further studies are needed in order to establish evidence-based standards for patient care. PMID- 27557957 TI - Environmental quality assessment of reservoirs impacted by Hg from chlor-alkali technologies: case study of a recovery. AB - Mercury (Hg) pollution legacy of chlor-alkali plants will be an important issue in the next decades with the planned phase out of Hg-based electrodes by 2025 within the Minamata convention. In such a context, the present study aimed to examine the extent of Hg contamination in the reservoirs surrounding the Oltchim plant and to evaluate the possible improvement of the environmental quality since the closure of its chlor-alkali unit. This plant is the largest chlor-alkali plant in Romania, which partly switched to Hg-free technology in 1999 and definitely stopped the use of Hg electrolysis in May 2012. Total Hg (THg) and methylmercury (CH3Hg) concentrations were found to decrease in the surface waters and sediments of the reservoirs receiving the effluents of the chlor-alkali platform since the closure of Hg units. Hence, calculated risk quotients (RQ) indicated no adverse effect of Hg for aquatic organisms from the ambient water exposure. RQ of Hg in sediments were mostly all higher than 1, showing important risks for benthic organisms. However, ecotoxicity testing of water and sediments suggest possible impact of other contaminants and their mixtures. Hg hotspots were found in soils around the platform with RQ values much higher than 1. Finally, THg and CH3Hg concentrations in fish were below the food safety limit set by the WHO, which contrasts with previous measurements made in 2007 revealing that 92 % of the studied fish were of high risk of consumption. Discontinuing the use of Hg electrodes greatly improved the surrounding environment of chlor-alkali plants within the following years and led to the decrease environmental exposure to Hg through fish consumption. However, sediment and soil still remained highly contaminated and problematic for the river reservoir management. The results of this ecological risk assessment study have important implications for the evaluation of the benefits as well as limits of the Minamata Convention implementation. PMID- 27557958 TI - Technical feasibility study of a low-cost hybrid PAC-UF system for wastewater reclamation and reuse: a focus on feedwater production for low-pressure boilers. AB - This study has applied the concept of the hybrid PAC-UF process in the treatment of the final effluent of the palm oil industry for reuse as feedwater for low pressure boilers. In a bench-scale set-up, a low-cost empty fruit bunch-based powdered activated carbon (PAC) was employed for upstream adsorption of biotreated palm oil mill effluent (BPOME) with the process conditions: 60 g/L dose of PAC, 68 min of mixing time and 200 rpm of mixing speed, to reduce the feedwater strength, alleviate probable fouling of the membranes and thus improve the process flux (productivity). Three polyethersulfone ultrafiltration membranes of molecular weight cut-off (MWCO) of 1, 5 and 10 kDa were investigated in a cross-flow filtration mode, and under constant transmembrane pressures of 40, 80, and 120 kPa. The permeate qualities of the hybrid processes were evaluated, and it was found that the integrated process with the 1 kDa MWCO UF membrane yielded the best water quality that falls within the US EPA reuse standard for boiler feed and cooling water. It was also observed that the permeate quality is fit for extended reuse as process water in the cement, petroleum and coal industries. In addition, the hybrid system's operation consumed 37.13 Wh m-3 of energy at the highest applied pressure of 120 kPa, which is far lesser than the typical energy requirement range (0.8-1.0 kWh m-3) for such wastewater reclamation. PMID- 27557959 TI - Guluronic acid content as a factor affecting turbidity removal potential of alginate. AB - Alginates are natural polymers composed of mannuronic and guluronic acid residues. They are currently extracted from brown algae; however, alginate can also be synthesized by some species of Azotobacter and Pseudomonas. Alginates with different proportion of mannuronic and guluronic acids are known to have different characteristics and form gels at different extents in the presence of calcium ions. The aim of this work was to investigate the usefulness of alginate as a non-toxic coagulant used in purification of drinking water. This study utilized alginates from Azotobacter vinelandii having different guluronic acid levels. These were obtained partly by changing the cultivation parameters, partly by epimerizing a purified alginate sample in vitro using the A. vinelandii mannuronan C-5 epimerase AlgE1. The different alginates were then used for coagulation together with calcium. The results showed that turbidity removal capability was dependent on the content of guluronic acid residues. For the best performing samples, the turbidity decreased from 10 NTU to 1 NTU by the use of only 2 mg/L of alginate and 1.5 mM of calcium chloride. PMID- 27557960 TI - Effects of taxonomy, sediment, and water column on C:N:P stoichiometry of submerged macrophytes in Yangtze floodplain shallow lakes, China. AB - Carbon (C), nitrogen (N) and phosphorus (P) are the three most important essential elements limiting growth of primary producers. Submerged macrophytes generally absorb nutrients from sediments by root uptake. However, the C:N:P stoichiometric signatures of plant tissue are affected by many additional factors such as taxonomy, nutrient availability, and light availability. We first revealed the relative importance of taxonomy, sediment, and water column on plant C:N:P stoichiometry using variance partitioning based on partial redundancy analyses. Results showed that taxonomy was the most important factor in determining C:N:P stoichiometry, then the water column and finally the sediment. In this study, a significant positive relationship was found between community C concentration and macrophyte community biomass, indicating that the local low C availability in macrophytes probably was the main reason why submerged macrophytes declined in Yangtze floodplain shallow lakes. Based on our study, it is suggested that submerged macrophytes in Yangtze floodplain shallow lakes are primarily limited by low light levels rather than nutrient availability. PMID- 27557961 TI - The implementation of data reconciliation for evaluating a full-scale petrochemical wastewater treatment plant. AB - Data reconciliation and mass balance analysis were conducted for the first time to improve the data obtained from a petrochemical wastewater treatment plant (WWTP), and the results were applied to evaluate the performance of the plant. Daily average values for 209 days from the inlet and outlet of the plant obtained from WWTP documentation center along with the results of four sampling runs in this work were used for data reconciliation and performance evaluation of the plant. Results showed that standard deviation and relative errors in the balanced data of each measurement decreased, especially for the process wastewater from 24.5 to 8.6 % for flow and 24.5 to 1.5 % for chemical oxygen demand (COD). The errors of measured data were -137 m3/day (-4.41 %) and 281 kg/day (7.92 %) for flow and COD, respectively. According to the balanced data, the removal rates of COD and 5-day biological oxygen demand (BOD5) through the aeration unit were equal to 37 and 46 %, respectively. In addition, the COD and BOD5 concentrations were reduced by about 61.9 % (2137 kg/day) and 78.1 % (1976 kg/day), respectively, prior to the biological process. At the same time, the removal rates of benzene, toluene, and styrene were 56, 38, and 69 %, respectively. The results revealed that about 40 % of influent benzene (75.5 kg/day) is emitted to the ambient air at the overhead of the equalization basin. It can be concluded that the volatilization of organic compounds is the basic mechanism for the removal of volatile organic compounds (VOCs) and it corresponds to the main part of total COD removal from the WWTP. PMID- 27557962 TI - From wetland to farm and back again: phosphorus dynamics of a proposed restoration project. AB - We studied the phosphorus dynamics in a former wetland, which had been converted to a celery farm, and now consists of two shallow, flooded ponds that are being proposed for aquatic habitat restoration. However, like many agricultural areas, this site is plagued by phosphorus legacy issues. Proposed restoration includes hydrologic reconnection of these ponds to its adjacent stream, which are now isolated from one another by an earthen berm, to create a wetland complex. One of the two flooded ponds was partially dredged, whereas the other one has remained undredged. Water column, sediment pore water, and sediment total phosphorus concentrations were significantly greater in the undredged pond compared to the dredged pond, but in both cases phosphorus levels in the water columns (mean TP 929 vs. 133 MUg/L in undredged vs. dredged ponds, respectively) would exacerbate downstream water quality issues if hydrologic reconnection occurred without first addressing the phosphorus issue. Sediment isotherm and maximum sorption data indicated that the sediments are close to phosphorus saturation in the undredged pond; simulated dredging of the cores revealed that exposure of deeper sediment layers would increase sorption capacity. Pore water SRP concentrations increased with sediment depth and were significantly greater in the undredged vs. dredged pond at both the 1-4-cm depth (2249 vs. 112 MUg/L) and 14-17-cm depth (5506 vs. 222 MUg/L). This study provides a framework for other projects that need to balance the competing demands of habitat restoration vs. water quality when restoring wetlands that have been converted to agricultural production. PMID- 27557963 TI - Determination of 210Po and 210Pb in red-capped scaber (Leccinum aurantiacum): bioconcentration and possible related dose assessment. AB - The paper presents the studies on 210Po and 210Pb activity determination in red capped scaber (Leccinum aurantiacum (Bulliard) Gray) collected in northern Poland. The aims of the studies were to determine 210Po and 210Pb content in analyzed mushrooms, evaluate the bioconcentration levels, and estimate possible related annual effective radiation dose to mushrooms consumers. The activities of 210Po and 210Pb in red-capped scaber were un-uniform and depended on sampling sites. But 210Po and 210Pb activity concentrations did not reflect their concentrations in topsoil. The results showed that the consumption of analyzed mushrooms should not increase significantly the total effective radiation dose from 210Po and 210Pb decay. PMID- 27557964 TI - Risk element sorption/desorption characteristics of dry olive residue: a technique for the potential immobilization of risk elements in contaminated soils. AB - Olive oil production is one of the most relevant agroindustrial activities in the Mediterranean region and generates a huge amount of both solid and semi-solid wastes, the uncontrolled disposal of which might lead to serious environmental problems. Due to its organic matter and mineral nutrient content, the waste material can be applied to agricultural soil as a fertilizer. However, due to its high organic matter content, dry olive residue (DOR), commonly called "alperujo," has the potential to immobilize risk elements in contaminated soils. The main objective of this study was to assess the possible effect of DOR on sorption of risk elements such as cadmium (Cd), lead (Pb), and zinc (Zn) in the soil. A set of batch sorption experiments were carried out to assess the ability of DOR to adsorb Cd, Pb, and Zn where the effect of the preceding biotransformation of DOR by four species of fungi: Penicillium chrysogenum, Coriolopsis floccosa, Bjerkhandera adusta, and Chondrostereum purpureum was compared. The Freundlich and Langmuir sorption isotherms were calculated to assess the sorption characteristics of both transformed and non-transformed DOR. The results showed good potential sorption capacity of DOR, especially for Pb and to a lesser extent for Cd and Zn. Better sorption characteristics were reported for the biotransformed DOR samples, which are expected to show higher humification of the organic matter. However, the desorption experiments showed weakness and instability of the DOR-bound elements, especially in the case of Zn. Thus, future research should aim to verify the DOR sorption pattern in contaminated soil as well as the potential stabilization of the DOR element bounds where the increase of the pH levels of the DOR samples needs to be taken into account. PMID- 27557965 TI - Estimation of plant sampling uncertainty: an example based on chemical analysis of moss samples. AB - In order to estimate the level of uncertainty arising from sampling, 54 samples (primary and duplicate) of the moss species Pleurozium schreberi (Brid.) Mitt. were collected within three forested areas (Wierna Rzeka, Piaski, Poslowice Range) in the Holy Cross Mountains (south-central Poland). During the fieldwork, each primary sample composed of 8 to 10 increments (subsamples) was taken over an area of 10 m2 whereas duplicate samples were collected in the same way at a distance of 1-2 m. Subsequently, all samples were triple rinsed with deionized water, dried, milled, and digested (8 mL HNO3 (1:1) + 1 mL 30 % H2O2) in a closed microwave system Multiwave 3000. The prepared solutions were analyzed twice for Cu, Fe, Mn, and Zn using FAAS and GFAAS techniques. All datasets were checked for normality and for normally distributed elements (Cu from Piaski, Zn from Poslowice, Fe, Zn from Wierna Rzeka). The sampling uncertainty was computed with (i) classical ANOVA, (ii) classical RANOVA, (iii) modified RANOVA, and (iv) range statistics. For the remaining elements, the sampling uncertainty was calculated with traditional and/or modified RANOVA (if the amount of outliers did not exceed 10 %) or classical ANOVA after Box-Cox transformation (if the amount of outliers exceeded 10 %). The highest concentrations of all elements were found in moss samples from Piaski, whereas the sampling uncertainty calculated with different statistical methods ranged from 4.1 to 22 %. PMID- 27557966 TI - Assessment of nitrogen losses through nitrous oxide from abattoir wastewater irrigated soils. AB - The land disposal of waste and wastewater is a major source of N2O emission. This is due to the presence of high concentrations of nitrogen (N) and carbon in the waste. Abattoir wastewater contains 186 mg/L of N and 30.4 mg/L of P. The equivalent of 3 kg of abattoir wastewater-irrigated soil was sieved and taken in a 4-L plastic container. Abattoir wastewater was used for irrigating the plants at the rates of 50 and 100 % field capacity (FC). Four crop species were used with no crop serving as a control. Nitrous oxide emission was monitored using a closed chamber technique. The chamber was placed inside the plastic container, and N2O emission was measured for 7 days after the planting. A syringe and pre evacuated vial were used for collecting the gas samples; a fresh and clean syringe was used each time to avoid cross-contamination. The collected gas samples were injected into a gas chromatography device immediately after each sampling to analyse the concentration of N2O from different treatments. The overall N2O emission was compared for all the crops under two different abattoir wastewater treatment rates (50 and 100 % FC). Under 100 % FC (wastewater irrigation), among the four species grown in the abattoir wastewater-irrigated soil, Medicago sativa (23 mg/pot), Sinapis alba (21 mg/pot), Zea mays (20 mg/pot) and Helianthus annuus (20 mg/pot) showed higher N2O emission compared to the 50 % treatments-M. sativa (17 mg/pot), S. alba (17 mg/pot), Z. mays (18 mg/pot) and H. annuus (18 mg/pot). Similarly, pots with plants have shown 15 % less emission than the pots without plants. Similar trends of N2O emission flux were observed between the irrigation period (4-week period) for 50 % FC and 100 % FC. Under the 100 % FC loading rate treatments, the highest N2O emission was in the following order: week 1 > week 4 > week 3 > week 2. On the other hand, under the 50 % FC loading rate treatments, the highest N2O emission was recorded in the first few weeks and in the following order: week 1 > week 2 > week 3 > week > 4. Since N2O is a greenhouse gas with high global warming potential, its emission from wastewater irrigation is likely to impact global climate change. Therefore, it is important to examine the effects of abattoir wastewater irrigation on soil for N2O emission potential. PMID- 27557967 TI - Concentrations, properties, and health risk of PM2.5 in the Tianjin City subway system. AB - A campaign was conducted to assess and compare the personal exposure in L3 of Tianjin subway, focusing on PM2.5 levels, chemical compositions, morphology analysis, as well as the health risk of heavy metal in PM2.5. The results indicated that the average concentration of the PM2.5 was 151.43 MUg/m3 inside the train of the subway during rush hours. PM2.5 concentrations inside car under the ground are higher than those on the ground, and PM2.5 concentrations on the platform are higher than those inside car. Regarding metal concentrations, the highest element in PM2.5 samples was Fe; the level of which is 17.55 MUg/m3. OC is a major component of PM2.5 in Tianjin subway. Secondary organic carbon is the formation of gaseous organic pollutants in subway. SEM-EDX and TEM-EDX exhibit the presence of individual particle with a large metal content in the subway samples. For small Fe metal particles, iron oxide can be formed easily. With regard to their sources, Fe-containing particles are generated mainly from mechanical wear and friction processes at the rail-wheel-brake interfaces. The non-carcinogenic risk to metals Cr, Ni, Cu, Zn and Pb, and carcinogenic hazard of Cr and Ni were all below the acceptable level in L3 of Tianjin subway. PMID- 27557968 TI - The influence of cosolvent and heat on the solubility and reactivity of organophosphorous pesticide DNAPL alkaline hydrolysis. AB - The presented research concerned the compatibility of cosolvents with in situ alkaline hydrolysis (ISAH) for treatment of organophosphorous (OPP) pesticide contaminated sites. In addition, the influence of moderate temperature heat increments was studied as a possible enhancement method. A complex dense non aqueous phase liquid (DNAPL) of primarily parathion (~50 %) and methyl parathion (~15 %) obtained from the Danish Groyne 42 site was used as a contaminant source, and ethanol and propan-2-ol (0, 25, and 50 v/v%) was used as cosolvents in tap water and 0.34 M NaOH. Both cosolvents showed OPP solubility enhancement at 50 v/v% cosolvent content, with slightly higher OPP concentrations reached with propan-2-ol. Data on hydrolysis products did not show a clear trend with respect to alkaline hydrolysis reactivity in the presence of cosolvents. Results indicated that the hydrolysis rate of methyl-parathion (MP3) decreased with addition of cosolvent, whereas the hydrolysis rate of ethyl-parathion (EP3) remained constant, and overall indications were that the hydrolysis reactions were limited by the rate of hydrolysis rather than NAPL dissolution. In addition to cosolvents, the influence of low-temperature heating on ISAH was studied. Increasing reaction temperature from 10 to 30 degrees C provided an average rate of hydrolysis enhancement by a factor of 1.4-4.8 dependent on the base of calculation. When combining 50 v/v% cosolvent addition and heating to 30 degrees C, EP3 solubility was significantly enhanced and results for O,O-diethyl thiophosphoric acid (EP2 acid) showed a significant enhancement of hydrolysis as well. However, this could not be supported by para-nitrophenol (PNP) data indicating the instability of this product in the presence of cosolvent. PMID- 27557969 TI - Binding characteristics of Cu2+ to natural humic acid fractions sequentially extracted from the lake sediments. AB - Humic acids (HAs) determine the distribution, toxicity, bioavailability, and ultimate fate of heavy metals in the environment. In this work, ten HA fractions (F1-F10) were used as adsorbent, which were sequentially extracted from natural sediments of Lake Wuliangsuhai, to investigate the binding characteristics of Cu2+ to HA. On the basis of the characterization results, differences were found between the ten extracted HA fractions responding to their elemental compositions and acidic functional groups. The characterization results reveal that the responses of ten extracted HA fractions to their elemental compositions and acidic functional groups were different. The O/C and (O + N)/C ratio of F1-F8 approximately ranged from 0.66 to 0.53 and from 0.72 to 0.61, respectively; the measured results showed that the contents of phenolic groups and carboxyl groups decreased from 4.46 to 2.60 mmol/g and 1.60 to 0.58 mmol/g, respectively. The binding characteristics of Cu2+ to the ten HA fractions were well modeled by the bi-Langmuir model; the binding behavior of Cu2+ to all the ten HA fractions were strongly impacted by pH and ionic strength. The FTIR and SEM-EDX image of HA fractions (pre- and post-adsorption) revealed that carboxyl and phenolic groups were responsible for the Cu2+ sorption on the ten sequentially extracted HA fractions process, which is the same with the analysis of the ligand binding and bi-Langmuir models Accordingly, the adsorption capacity of the former HA fractions on Cu2+ were higher than the latter ones, which may be attributed to the difference of carboxyl and phenolic group contents between the former and latter extracted HA fractions. Additionally, the functional groups with N and S should not be neglected. This work is hopeful to understand the environmental effect of humic substances, environmental geochemical behavior, and bioavailability of heavy metals in lakes. PMID- 27557970 TI - Electrochemical treatment of shrimp farming effluent: role of electrocatalytic material. AB - This study investigated the electrochemical oxidation of organic matter present in shrimp farming effluent using three types of electrocatalytic materials: Ti/Ru0.34Ti0.66O2, Ti/Pt, and boron-doped diamond (BDD). An electrochemical cell with 300 mL under stirring agitation was used by applying 20, 40, and 60 mA cm-2. A Ti/Ru0.34Ti0.66O2 anode showed a reduction of chemical oxygen demand (COD) about 84 % after 1 h of electrolysis, while at the same time, 71 % of COD decay was achieved at Ti/Pt. Conversely, only 71 % of COD was removed after 2 h with a BDD anode. Regarding the temperature effect, BDD showed better performances than those achieved for Ti/Ru0.34Ti0.66O2 and Ti/Pt anodes during an electrochemical treatment of a shrimp farming effluent, obtaining 72 % of COD removal by applying 20 mA cm-2 at 40 degrees C after 15 min. Energy consumption and cost were estimated in order to established the engineering applicability of this alternative process. PMID- 27557971 TI - Late season pharmaceutical fate in wetland mesocosms with and without phosphorous addition. AB - The fate of six human-use drugs was assessed and predicted in mesocosms designed to mimic shallow constructed wetlands during the onset of fall and senescence. Mesocosms were monitored for 28 days after the addition of carbamazepine, clofibric acid, fluoxetine and naproxen (nominal initial concentrations of 5 MUg/L each), sulfamethoxazole, and sulfapyridine (nominal initial concentrations of 150 MUg/L each), with and without phosphorous (P) addition at 1.6 mg/L. We hypothesized that addition of P would stimulate primary productivity and enhance removal of pharmaceuticals from the water column. Carbamazepine, clofibric acid, fluoxetine, and naproxen had half-lives of 8.7, 11, 1.5, and 2.5, and 8.6, 11.0, 1.4, and 2.5 days in treatments with and without P amendment, respectively. Sulfamethoxazole and sulfapyridine had half-lives of 17 and 4.9 days in mesocosms with P amendment and 17 and 4.7 days without amendment. A concurrent pulse of P with pharmaceuticals did not significantly enhance the removal of these compounds. Predicted half-lives from modeling efforts were consistent with observed values, with photolysis the greatest contributor to chemical attenuation. PMID- 27557972 TI - Microbial biotransformation of furosemide for environmental risk assessment: identification of metabolites and toxicological evaluation. AB - Some widely prescribed drugs are sparsely metabolized and end up in the environment. They can thus be a focal point of ecotoxicity, either themselves or their environmental transformation products. In this context, we present a study concerning furosemide, a diuretic, which is mainly excreted unchanged. We investigated its biotransformation by two environmental fungi, Aspergillus candidus and Cunninghamella echinulata. The assessment of its ecotoxicity and that of its metabolites was performed using the Microtox test (ISO 11348-3) with Vibrio fischeri marine bacteria. Three metabolites were identified by means of HPLC-MS and 1H/13C NMR analysis: saluamine, a known pyridinium derivative and a hydroxy-ketone product, the latter having not been previously described. This hydroxy-ketone metabolite was obtained with C. echinulata and was further slowly transformed into saluamine. The pyridinium derivative was obtained in low amount with both strains. Metabolites, excepting saluamine, exhibited higher toxicity than furosemide, being the pyridinium structure the one with the most elevated toxic levels (EC50 = 34.40 +/- 6.84 mg L-1). These results demonstrate that biotic environmental transformation products may present a higher environmental risk than the starting drug, hence highlighting the importance of boosting toxicological risk assessment related to the impact of pharmaceutical waste. PMID- 27557973 TI - Combined effects of nitrogen addition and organic matter manipulation on soil respiration in a Chinese pine forest. AB - The response of soil respiration (Rs) to nitrogen (N) addition is one of the uncertainties in modelling ecosystem carbon (C). We reported on a long-term nitrogen (N) addition experiment using urea (CO(NH2)2) fertilizer in which Rs was continuously measured after N addition during the growing season in a Chinese pine forest. Four levels of N addition, i.e. no added N (N0: 0 g N m-2 year-1), low-N (N1: 5 g N m-2 year-1), medium-N (N2: 10 g N m-2 year-1), and high-N (N3: 15 g N m-2 year-1), and three organic matter treatments, i.e. both aboveground litter and belowground root removal (LRE), only aboveground litter removal (LE), and intact soil (CK), were examined. The Rs was measured continuously for 3 days following each N addition application and was measured approximately 3-5 times during the rest of each month from July to October 2012. N addition inhibited microbial heterotrophic respiration by suppressing soil microbial biomass, but stimulated root respiration and CO2 release from litter decomposition by increasing either root biomass or microbial biomass. When litter and/or root were removed, the "priming" effect of N addition on the Rs disappeared more quickly than intact soil. This is likely to provide a point of view for why Rs varies so much in response to exogenous N and also has implications for future determination of sampling interval of Rs measurement. PMID- 27557974 TI - Experimental studies and kinetic modeling of the growth of phenol-degrading bacteria in turbulent fluids. AB - Understanding the interaction between microorganisms and fluid dynamics is important for aquatic ecosystems, though only sporadic attention has been focused on this topic in the past. In this study, particular attention was paid to the phenol-degrading bacterial strains Microbacterium oxydans LY1 and Alcaligenes faecalis LY2 subjected to controlled fluid flow under laboratory conditions. These two strains were found to be able to degrade phenols over a concentration range from 50 to 500 mg/L under different turbulence conditions ranging from 0 to 250 rpm. The time it took to reach total phenol degradation decreased when the turbulence was increased in both strains, with increasing energy dissipation rates ranging from 0.110 to 6.241 W/kg, corresponding to changes in the bacterial diffusive sublayer thickness (delta) and enhanced oxygen uptake. Moreover, the maximum specific growth rates of the two strains also increased with the enhancement of turbulence. A model integrating growth inhibition and fluid motion was proposed based on the self-inhibition Haldane model by introducing a turbulence parameter, alpha. The resulting modified Haldane model was designed to include fluid motion as a variable in the quantification of the physiological responses of microorganisms. This modified Haldane model could be considered a useful laboratory reference when modeling procedures for water environment bioremediation. Graphical abstract Cell nutrition uptake cartoon schematic diagram for M. oxydans LY1 under different turbulent condition (50 and 200 rpm). PMID- 27557976 TI - Cretaceous origin of giant rhinoceros beetles (Dynastini; Coleoptera) and correlation of their evolution with the Pangean breakup. AB - The giant rhinoceros beetles (Dynastini, Scarabaeidae, Coleoptera) are distributed in tropical and temperate regions in Asia, America and Africa. Recent molecular phylogenetic studies have revealed that the giant rhinoceros beetles can be divided into three clades representing Asia, America and Africa. Although a correlation between their evolution and the continental drift during the Pangean breakup was suggested, there is no accurate divergence time estimation among the three clades based on molecular data. Moreover, there is a long chronological gap between the timing of the Pangean breakup (Cretaceous: 110-148 Ma) and the emergence of the oldest fossil record (Oligocene: 33 Ma). In this study, we estimated their divergence times based on molecular data, using several combinations of fossil calibration sets, and obtained robust estimates. The inter continental divergence events among the clades were estimated to have occurred about 99 Ma (Asian clade and others) and 78 Ma (American clade and African clade), both of which are after the Pangean breakup. These estimates suggest their inter-continental divergences occurred by overseas sweepstakes dispersal, rather than by vicariances of the population caused by the Pangean breakup. PMID- 27557975 TI - Effects of doping amounts of potassium ferricyanide with titanium dioxide and calcination durations on visible-light degradation of pharmaceuticals. AB - Acetaminophen (ACT) is one of the most frequently detected pharmaceuticals in aqueous environments, and treatment of ACT were generally carried out by photocatalytic degradations under high energy UV irradiation. In this study, potassium ferricyanide was utilized as a quadruple-elemental dopant in a TiO2 photocatalyst in order to enhance its visible-light activity. Two critical parameters (amounts of dopants and durations of calcination) of the synthesis of the photocatalyst by a sol-gel method were systematically evaluated. Crystal structure of the doping TiO2 was examined by X-ray diffraction while the effects of the two parameters on the photocatalytic activity were elucidated by various characterizations. Increasing the amount of dopant or the duration of calcination red-shifted the UV-vis DRS of the doped TiO2. The estimated band gap energy of the doped TiO2 decreased slightly as the amount of dopant increased, but it increased as the duration of calcination increased. The FT-IR yielded characteristic peaks that revealed the effects of the two parameters, whereas the SEM images revealed the morphological evolutions of each effect. The photocatalyst, synthesized at optimum conditions was able to remove 99.1 % acetaminophen with rate constant of 7.9 * 10-3 min-1, which was 4.88 times greater than virgin TiO2. In general, this study not only optimized synthetic conditions of the new visible-light active photocatalyst for ACT degradation but also presented characterizations conducted by SEM, XRD, UV-vis DRS, and FTIR to elucidate the relationship between modified structure and the photocatalytic activity. Graphical abstract Effects of doping amounts of K3[Fe(CN)6] and calcunation duration on visible light absorbance of TiO2 photocatalysts. PMID- 27557977 TI - Experiences of patients with traumatic brain injury and their carers during transition from in-patient rehabilitation to the community: a qualitative study. AB - PURPOSE: To explore the experiences of individuals who have had a severe traumatic brain injury (TBI) and their carers in the first month post-discharge from in-patient rehabilitation into living in the community. METHOD: Using a qualitative approach underpinned by critical realism, we explored the narratives of 10 patients and nine carers using semi-structured interviews approximately one month post-discharge. Thematic analysis was carried out independently by two researchers. RESULTS: Firstly, perceptions of support were mixed but many patients and carers felt unsupported in the inpatient phase, during transitions between units and when preparing for discharge. Secondly, they struggled to accept a new reality of changed abilities, loss of roles and loss of autonomy. Thirdly, early experiences post-discharge exacerbated fears for the future. CONCLUSIONS: Most patients and carers struggled to identify a cohesive plan that supported their transition to living in the community. Access to services required much persistence on the part of carers and tended to be short-term, and therefore did not meet their long-term needs. We propose the need for a case manager to be involved at an early stage of their rehabilitation and act as a key point for information and access to on-going rehabilitation and other support services. Implications for Rehabilitation Traumatic Brain Injury (TBI) is a major cause of long-term disability. It can affect all areas of daily life and significantly reduce quality of life for both patient and carer. Professionals appear to underestimate the change in abilities and impact on daily life once patients return home. Community services maintain a short-term focus, whereas patients and carers want to look further ahead - this dissonance adds to anxiety. The study's findings on service fragmentation indicate an urgent need for better integration within health services and across health, social care and voluntary sectors. A link person/case manager who oversees the patient journey from admission onwards would help improve integrated care and ensure the patient, and carer, are at the center of service provision. PMID- 27557980 TI - The Unseen and the Unheard in Fiction and Memoir. PMID- 27557979 TI - Triphenylphosphane Pt(II) complexes containing biologically active natural polyphenols: Synthesis, crystal structure, molecular modeling and cytotoxic studies. AB - Platinum complexes bearing phosphane ligands in cis configuration with deprotonated flavonoids (3-hydroxyflavone, quercetin) and deprotonated ethyl gallate were synthesized starting from cis-[PtCl2(PPh3)2]. In all cases, O,O' chelate structures were obtained. While quercetin and ethyl gallate complexes are quite stable in solution, the 3-hydroxyflavonate complex undergoes a slow aerobic photodegradation in solution with formation of salicylic and benzoic acids. The X ray diffraction structures of quercetin and ethyl gallate complexes are reported. Cell cycle studies (in the dark) of the complexes in two human cell lines revealed that the cytotoxic activity of the complex bearing 3-hydroxyflavonate is higher than those exhibited by 3-hydroxyflavone or by cis-[PtCl2(PPh3)2] alone. Density functional theory studies on the hydrolysis pathway for the 3 hydroxyflavone and ethyl gallate complexes explained the different cytotoxic activity observed for the two compounds on the basis of the different intermediates formed during hydrolysis (relatively inert hydroxy Pt complexes for ethyl gallate and monoaqua complexes for 3-hydroxyflavone). PMID- 27557978 TI - Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Oxidative Stress in Zebrafish Hair Cells. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide, with known antiapoptotic functions. Our previous in vitro study has demonstrated the ameliorative role of PACAP-38 in chicken hair cells under oxidative stress conditions, but its effects on living hair cells is now yet known. Therefore, the aim of the present study was to investigate in vivo the protective role of PACAP-38 in hair cells found in zebrafish (Danio rerio) sense organs-neuromasts. To induce oxidative stress the 5-day postfertilization (dpf) zebrafish larvae were exposed to 1.5 mM H2O2 for 15 min or 1 h. This resulted in an increase in caspase-3 and p-38 MAPK level in the hair cells as well as in an impairment of the larvae basic behavior. To investigate the ameliorative role of PACAP-38, the larvae were incubated with a mixture of 1.5 mM H2O2 and 100 nM PACAP-38 following 1 h preincubation with 100 nM PACAP-38 only. PACAP-38 abilities to prevent hair cells from apoptosis were investigated. Whole-mount immunohistochemistry and confocal microscopy analyses revealed that PACAP-38 treatment decreased the cleaved caspase-3 level in the hair cells, but had no influence on p-38 MAPK. The analyses of basic locomotor activity supported the protective role of PACAP-38 by demonstrating the improvement of the fish behavior after PACAP-38 treatment. In summary, our in vivo findings demonstrate that PACAP 38 protects zebrafish hair cells from oxidative stress by attenuating oxidative stress-induced apoptosis. PMID- 27557981 TI - Neoglottis reconstruction with sternohyoid muscles on upper-tracheal orifice after laryngectomy. AB - Ideal speech restoration remains a difficult challenge for patients undergoing laryngectomy so far. Our aim was to explore the feasibility of neoglottic reconstruction with sternohyoid muscles on upper-tracheal orifice after total laryngectomy which can obtain relatively ideal voice rehabilitation. Fifteen male patients are laryngectomized, of whom eight with standard total laryngectomy and seven underwent nonstandard total laryngectomy with epiglottis conserved. After laryngectomy, the upper margin of the anterior hypopharyngeal mucosa (postcricoid mucosa) was stitched to the posterior margin of upper-tracheal orifice and a triangle-shaped neoglottis on upper-tracheal orifice was reconstructed using bilateral sternohyoid muscles near the hyoid bone which were sutured to the posterior wall and bilateral of upper-tracheal orifice. Then tracheolingual root anastomosis was done and reconstruction surgery was completed. Finally, a satisfactory voice was achieved in 14 of 15 patients except one whose neoglottis is stenosed and 11 cases had no severe complications including aspiration erroneous deglutition. The stomach catheters were removed successfully from 4 to 6 weeks after surgery in 11 cases, respectively. The neoglottis had to be closed in three patients because of aspiration problem. One neoglottis was closed 3 weeks after surgical reconstruction because of tracheal rings tear which created a bigger neoglottis. One neoglottis was removed 32 moths after total laryngectomy due to big neoglottis. Another one was closed 3 weeks after surgery by reason of the fear of aspiration without psychological preparation. Therefore, it is feasible to use the sternohyoid muscles for creation of a neoglottis on upper tracheal orifice and provide an alternative surgical method of the voice restoration for the patients after laryngectomy. PMID- 27557982 TI - Non-falciparum malaria in Dakar: a confirmed case of Plasmodium ovale wallikeri infection. AB - BACKGROUND: Plasmodium ovale is rarely described in Senegal. A case of clinical malaria due to P. ovale wallikeri in West Central of Senegal is reported. CASE: A 34-year-old male baker in Dakar, with no significant previous medical history, was admitted to a health clinic with fever and vomiting. Fever had been lasting for 4 days with peaks every 48 h. As monospecific Plasmodium falciparum HRP-2 RDT was negative, he was treated with antibiotics. However, owing to persisting symptoms, he was referred to the emergency unit of the Youssou Mbargane Diop Hospital, Dakar, Senegal. Clinical examination found impaired general condition. All other physical examinations were normal. Laboratory tests showed anaemia (haemoglobin 11.4 g/dl), severe thrombocytopaenia (platelets 30 * 10(9)/mm(3)), leukopenia (3650/mm(3)), lymphocytopenia (650/mm(3)). Renal function was normal as indicated by creatininaemia and uraemia (11 mg/l and 0.25 g/l, respectively) and liver enzymes were slightly elevated (aspartate aminotransferase 77 UI/l and alanine aminotransferase 82 UI/l). Blood smear evaluations in Parasitology Laboratory of Aristide Le Dantec Hospital showed malaria parasites of the species P. ovale with a 0.08 % parasitaemia. Molecular confirmation was done by real time PCR targeting the 18S rRNA gene. The P. ovale infection was further analysed to species level targeting the potra gene and was identified as P. ovale wallikeri. According to the hospital's malaria treatment guidelines for severe malaria, treatment consisted of intravenous quinine at hour 0 (start of treatment) and 24 h after initial treatment, followed by artemether-lumefantrine 24 h later. A negative microscopy was noted on day 3 post-treatment and the patient reported no further symptoms. CONCLUSION: Malaria due to non-falciparum species is probably underestimated in Senegal. RDTs specific to non-falciparum species and/or pan specific RDTs should be included as tools of diagnosis to fight against malaria in Senegal. In addition, a field-deployable molecular tool such as the loop mediated isothermal amplification can be considered as an additional useful tool to detect low malaria parasite infections and for speciation. In addition, national malaria control policies should consider other non-falciparum species in treatment guidelines, including the provision of primaquine for the treatment of relapsing parasites. PMID- 27557983 TI - A Comparison of the Regional Circulation in the Feet between Dialysis and Non Dialysis Patients using Indocyanine Green Angiography. AB - BACKGROUND AND AIMS: Peripheral artery disease in dialysis cases is more prone to critical limb ischemia compared to non-dialysis cases, with a significantly high rate of major amputation of the lower limbs. Lesions are distributed on the more distal side in dialysis critical limb ischemia cases. The aim of this study was to investigate the usefulness of indocyanine green angiography to determine differences in the regional circulation in the foot between dialysis and non dialysis patients. MATERIALS AND METHODS: The subjects included 62 cases, among which 20 were dialysis patients and 42 were non-dialysis patients. We compared the indocyanine green angiography parameters for regions of interest in the dialysis and non-dialysis groups, which included the magnitude of intensity from indocyanine green onset to maximum intensity (Imax), the time from indocyanine green onset to maximum intensity (Tmax), the time elapsed from the fluorescence onset to half the maximum intensity (T1/2), and the time from maximum intensity to declining to 90% of the maximum intensity (Td90%). These indocyanine green angiography parameters were measured at region of interest 1 (the Chopart joint), region of interest 2 (the Lisfranc joint), and region of interest 3 (the distal region of the first metatarsal bone). RESULTS: In the comparison between the dialysis and non-dialysis groups, a significant difference was observed regarding Tmax, T1/2, and Td90%, especially in region of interest 3. CONCLUSION: In this study, we show that regional tissue perfusion is more deteriorated in dialysis patients compared with non-dialysis patients using indocyanine green angiography. Tmax, T1/2, and Td90% could be useful clinical parameters to compare ischemic severity of the lower limb between dialysis and non-dialysis patients. PMID- 27557984 TI - Reactions to Testing HIV Negative: Measurement and Associations with Sexual Risk Behaviour Among Young MSM Who Recently Tested HIV Negative. AB - Receiving an HIV-positive test result is associated with reduced condomless anal sex (CAS), but little is known about negative test results. The recent development of the Inventory of Reactions to Testing HIV Negative confirmed that there are diverse reactions to receiving a negative test result, which have implications for risk behaviour. The goals of the current study were to validate the measure in a sample of young men who have sex with men who recently tested HIV-negative (N = 1113) and to examine its associations with CAS. Factor analysis identified four factors, three of which were the same as the original factors (Reinforced Safety, Luck, and Invulnerability) and one that was novel (Reinforced Risk). Construct validity was demonstrated with associations between subscales and constructs from the IMB model of HIV prevention. Lower Reinforced Safety and higher Luck and Reinforced Risk were associated with more CAS. Associations between Reinforced Safety and Luck with CAS were stronger for those who reported more lifetime HIV tests. Findings highlight the importance of reactions to testing HIV-negative and suggest that they become more important with repeated testing. PMID- 27557985 TI - Acceptability of HIV Testing Sites Among Rural and Urban African Americans Who Use Cocaine. AB - African Americans (AAs) who use cocaine in the Southern region of the U.S. have a relatively high risk of HIV and need for HIV testing. Among this group, those residing in rural areas may have less favorable opinions about common HIV testing sites, which could inhibit HIV testing. We examined rural/urban variations in their acceptability of multiple HIV testing sites (private physician clinic, local health department, community health center, community HIV fair, hospital emergency department, blood plasma donation center, drug abuse treatment facility, and mobile van or community outreach worker). Results from partial proportional odds and logistic regression analyses indicate that rural AA who use cocaine have lower odds of viewing local health departments (OR = 0.09, 95 % CI = 0.03-0.21), physician offices (OR = 0.19, 95 % CI = 0.09-0.42), and drug use treatment centers (OR = 0.49; 95 % CI = 0.30-0.80) as acceptable relative to their urban counterparts. The findings have implications for further targeting HIV testing toward AAs who use of cocaine, particularly those residing in the rural South. PMID- 27557986 TI - What Messages are Adolescent Voluntary Medical Male Circumcision (VMMC) Clients Getting and How? Findings From an Observational Study in Tanzania. AB - Uncircumcised adolescent males in sub-Saharan Africa are an important group to reach with voluntary medical male circumcision (VMMC) services due to high HIV burden occurring among this age group. Appropriateness of the content and delivery of sexual health and HIV prevention messages to adolescent VMMC clients has not been extensively described. A study was conducted in Tanzania to examine quality, delivery and content of messages provided to adolescent (aged 15-19) and adult (aged 20+) VMMC clients (n = 320). Results show that counseling of mixed age groups during group education lacked selected key messages, compared to more age-homogeneous groups. Additionally, adolescents received more comprehensive information in individual counseling compared to group education. We recommend that health care providers are provided with skills and job aides to assist them to segment VMMC clients by age; provide age-appropriate messages; and increase use of individual counseling as a means to communicate with adolescent clients. PMID- 27557987 TI - HIV Prevalence and Risk Factors Among Male Foreign Migrants in Cape Town, South Africa. AB - While migration has been shown to be a risk factor for HIV, variation in HIV prevalence by subgroups of migrants needs further exploration. This paper documents the HIV prevalence and key characteristics among male foreign migrants in Cape Town, South Africa and the effectiveness of respondent-driven sampling (RDS) to recruit this population. Participants in this cross-sectional study completed a behavioral risk-factor questionnaire and provided a dried blood sample for HIV analysis. Overall HIV prevalence was estimated to be 8.7 % (CI 5.4 11.8) but varied dramatically by country of origin. After adjusting for country of origin, HIV sero-positivity was positively associated with older age (p = 0.001), completing high school (p = 0.025), not having enough money for food (p = 0.036), alcohol use (p = 0.049), and engaging in transactional sex (p = 0.022). RDS was successful in recruiting foreign migrant men. A better understanding of the timing of HIV acquisition is needed to design targeted interventions for migrant men. PMID- 27557988 TI - Characterization of the peripheral thyroid system of gilthead seabream acclimated to different ambient salinities. AB - Thyroid hormones are involved in many developmental and physiological processes, including osmoregulation. The regulation of the thyroid system by environmental salinity in the euryhaline gilthead seabream (Sparus aurata) is still poorly characterized. To this end seabreams were exposed to four different environmental salinities (5, 15, 40 and 55ppt) for 14days, and plasma free thyroid hormones (fT3, fT4), outer ring deiodination and Na+/K+-ATPase activities in gills and kidney, as well as other osmoregulatory and metabolic parameters were measured. Low salinity conditions (5ppt) elicited a significant increase in fT3 (29%) and fT4 (184%) plasma concentrations compared to control animals (acclimated to 40ppt, natural salinity conditions in the Bay of Cadiz, Spain), while the amount of pituitary thyroid stimulating hormone subunit beta (tshb) transcript abundance remained unchanged. In addition, plasma fT4 levels were positively correlated to renal and branchial deiodinase type 2 (dio2) mRNA expression. Gill and kidney T4 outer ring deiodination activities correlated positively with dio2 mRNA expression and the highest values were observed in fish acclimated to low salinities (5 and 15ppt). The high salinity (55ppt) exposure caused a significant increase in tshb expression (65%), but deiodinase gene expression (dio1 and dio2) and activity did not change and were similar to controls (40ppt). In conclusion, acclimation to different salinities led to changes in the peripheral regulation of thyroid hormone metabolism in seabream. Therefore, thyroid hormones are involved in the regulation of ion transport and osmoregulatory physiology in this species. The conclusions derived from this study may also allow aquaculturists to modulate thyroid metabolism in seabream by adjusting culture salinity. PMID- 27557989 TI - Physiological effects of hypoxic conditions during the plateau period on the chicken embryo. AB - The chick embryo employs several adaptive responses to hypoxic challenges, affecting both metabolism and oxygen (O2) transport. The present study assessed the effects of hypoxic conditions (17% O2) during the plateau phase on embryonic metabolic rate, cardiovascular parameters, and development up to hatching. The study was divided into 2 experiments: (1) Control; 17% O2 for 6h/d on E16-E18 (6H), and 17% O2 for 12h/d on E16-E18 (12H), and (2) Control; 12H, and 17% O2 continuously for 72h on E16-E18, (72H). Hypoxic embryos exhibited a significant increase in heart rate and an upward trend starting on E17 in hematocrit and hemoglobin levels. We observed a decrease in metabolism in 12H and 72H embryos during the plateau period; their oxygen consumption as well as yolk consumption were lower compared to Control and they hatched with a significantly lower body temperature, indicating lower heat production. There was no evidence of adaptation or long-term effects of exposure to 17% O2 for 6h/d. Exposure to 72h of hypoxic conditions led to significant physiological changes and had a detrimental influence on embryonic development and growth. In contrast, exposure to 12h/d produced moderate hypoxic changes, which helped the embryo to cope with the stress without significant influences on its growth and development. The decrease in metabolism may represent a metabolic adaptation through a decrease in resting metabolic rate and lower heat production. Such alterations may affect post-hatch performance and energy allocation between maintenance and growth, especially under stress when there is increased oxygen demand. PMID- 27557990 TI - The expression of VILL protein is hypoosmotic-dependent in the lamellar gill ionocytes of Otocephala teleost fish, Chanos chanos. AB - Milkfish, a species within the primitive teleost lineage Otocephala, can survive in water conditions ranging from hypo- to hyper-saline. This study explored the effects of environmental salinity on apical morphologies of ionocytes and the expression of villin homologs in the gills of milkfish acclimated to either seawater (SW) or fresh water (FW). Scanning electron microscopy revealed that the ionocytes in the gill filaments of SW and FW milkfish, respectively, cellular apical morphologies were hole-type and squint-type. The flat-type ionocytes were observed in the gill lamellae of FW milkfish. Furthermore, apical surfaces of some lamellar ionocytes exhibited microvilli. Villin 1 is a microvilli marker expressed in the epithelial cells of various vertebrates. In the phylogenetic tree of villin 1 homologs, primitive teleosts exhibit villin 1-like (VILL) and villin 1 proteins. Two mRNA sequences, villin 1 and VILL, were identified from the milkfish transcriptome by next generation sequencing. Low but constant expression of villin 1 (gene and protein) was observed in the gills for both SW and FW fish. VILL gene and protein expression levels in the gills were higher in FW fish, compared to SW fish. Double immunofluorescence staining demonstrated that VILL protein was present in some lamellar ionocytes of FW milkfish, but not in the filament ionocytes of either FW or SW milkfish. Taken together, these findings indicated that the VILL expression of ionocytes is hypoosmotic dependent. The VILL might be involved in the formation of microvilli in the lamellar ionocytes for hyperosmoregulation of the milkfish. PMID- 27557991 TI - Comparison between a fixed-dose contrast protocol and a weight-based contrast dosing protocol in abdominal CT. AB - AIM: To compare a fixed-dose intravenous iodinated contrast medium protocol with weight-based dosing protocols for abdominal computed tomography (CT). MATERIALS AND METHODS: Fifty patients were scanned using a fixed-dose protocol, 50 patients were scanned using a full-dose weight-based contrast dosing protocol, and 13 patients were scanned using a reduced dose weight-based protocol. Radiodensity was measured at the portal vein, aorta, spleen, and liver. These values were plotted against contrast medium dose per unit weight. Images from all patients were anonymised and presented to two independent consultants who subjectively assessed contrast enhancement using a five-point Likert scale. RESULTS: Using a fixed-dose protocol, there was a statistically significant negative correlation and trend between patient weight and radiodensity at the portal vein, aorta, spleen, and liver. Using a full-dose weight-based contrast dosing protocol, there was no longer a statistically significant correlation or trend implying a more consistent degree of enhancement over a spectrum of patient weights. In addition, when the full-dose weight-based contrast dosing protocol was used, there was a statistically significant increase in the number of scans subjectively assessed as having ideal enhancement and a statistically significant decrease in the number of scans felt to have excessive enhancement when compared to a fixed-dose protocol. The weight-based dosing protocol used less contrast medium than the fixed-dose protocol and there was no evidence of contrast-induced acute kidney injury (CIAKI) in any of the patients that received a greater dose than that which they would have received using a fixed-dose protocol. The reduced-dose weight-based protocol showed less objective enhancement of the portal vein, abdominal aorta, spleen, and liver compared to the full-dose protocol and a reduction in the number of scans perceived as showing ideal enhancement. There was, however, no increase in the number of scans with poor or non-diagnostic enhancement. CONCLUSION: Weight-based contrast medium dosing has been shown to objectively provide more consistent vessel and solid-organ enhancement and subjectively improve image quality across a spectrum of weights. Depending on mean patient mass, it has also been shown to reduce overall contrast medium dose, and there is no evidence of CIAKI in patients that receive larger doses. This study also postulates that a standardised approach to contrast medium dose reduction in patients with renal impairment may be a viable strategy. PMID- 27557992 TI - A life on the wild side. PMID- 27557993 TI - Acellular mineral deposition within injectable, dual-gelling hydrogels for bone tissue engineering. AB - This study sought to characterize the composition and morphology of acellular mineralization occurring in thermally and chemically gelable hydrogels comprising copolymers of hydrophobic N-isopropylacrylamide as a function of hydrogel hydrophobicity and culture medium formulation. The deposition of calcium phosphate (CaP) mineral was hypothesized to occur with increasing hydrogel hydrophobicity and presence of serum proteins in the culture medium. Two hydrogel compositions with a solid content of 15 and 20 wt % were examined in serum containing and nonserum-containing media for 0, 14, 28, and 56 days. Using biochemical assays, calcium, but not phosphate content, was found to significantly increase over time in hydrophobic hydrogels soaked in cell culture medium with fetal bovine serum. Significant increases in the calcium to phosphate ratio were observed within these hydrogels from day 0 to 56, with mineralization indicated by von Kossa histological staining. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) were used to analyze CaP mineral characteristics. No crystalline apatitic reflection peaks were observed using XRD, which was supported by the lack of observable mineral deposits as observed using SEM/EDX. However, FTIR showed the presence of new absorption peaks in the serum-containing samples at 28 and 56 days which suggested the formation of an immature apatitic-like mineral. The ability to undergo hydrophobicity-dependent and protein-mediated mineralization demonstrates the potential of these dual gelling hydrogels as acellular self-mineralizing materials for bone tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 110-117, 2017. PMID- 27557994 TI - The Societal Cost of Schizophrenia: A Systematic Review. AB - BACKGROUND: Cost-of-illness (COI) studies provide useful information on the economic burden that schizophrenia imposes on a society. OBJECTIVES: This study aims to give a general overview of COI studies for schizophrenia and to compare the societal cost of schizophrenia across countries. It also aims to identify the main cost components of schizophrenia and factors associated with higher societal cost to improve the quality and reporting of COI studies for schizophrenia. METHODS: We performed an electronic search on multiple databases (MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Health Management Information Consortium [HMIC] and the System for Information on Grey Literature [openSIGLE]) to identify COI studies of schizophrenia published between 1996 and 2016. The primary outcome of this review was societal cost per schizophrenia patient, by cost component. All costs were converted to $US, year 2015 values. RESULTS: We included 19 studies in this review. The annual societal cost per patient varied from $US5818 in Thailand to $US94,587 in Norway; whereas the lifetime societal cost per patient was estimated to be $US988,264 in Australia (all year 2015 values). The main cost drivers were direct healthcare costs and productivity losses. Factors associated with higher individual costs included patient demographics, severity of disease and methods used to calculate the costs of productivity losses and comorbidities. CONCLUSIONS: This review highlights the large economic burden of schizophrenia. The magnitude of the cost estimates differs considerably across countries, which might be caused by different economic conditions and healthcare systems and widespread methodological heterogeneity among COI studies. Proposed recommendations based on this review can be used to improve the consistency and comparability of COI studies for schizophrenia. PMID- 27557995 TI - Mapping Between the Sydney Asthma Quality of Life Questionnaire (AQLQ-S) and Five Multi-Attribute Utility Instruments (MAUIs). AB - PURPOSE: Economic evaluation of health services commonly requires information regarding health-state utilities. Sometimes this information is not available but non-utility measures of quality of life may have been collected from which the required utilities can be estimated. This paper examines the possibility of mapping a non-utility-based outcome, the Sydney Asthma Quality of Life Questionnaire (AQLQ-S), onto five multi-attribute utility instruments: Assessment of Quality of Life 8 Dimensions (AQoL-8D), EuroQoL 5 Dimensions 5-Level (EQ-5D 5L), Health Utilities Index Mark 3 (HUI3), 15 Dimensions (15D), and the Short Form 6 Dimensions (SF-6D). METHODS: Data for 856 individuals with asthma were obtained from a large Multi-Instrument Comparison (MIC) survey. Four statistical techniques were employed to estimate utilities from the AQLQ-S. The predictive accuracy of 180 regression models was assessed using six criteria: mean absolute error (MAE), root mean squared error (RMSE), correlation, distribution of predicted utilities, distribution of residuals, and proportion of predictions with absolute errors <0.0.5. Validation of initial 'primary' models was carried out on a random sample of the MIC data. RESULTS: Best results were obtained with non-linear models that included a quadratic term for the AQLQ-S score along with demographic variables. The four statistical techniques predicted models that performed differently when assessed by the six criteria; however, the best results, for both the estimation and validation samples, were obtained using a generalised linear model (GLM estimator). CONCLUSIONS: It is possible to predict valid utilities from the AQLQ-S using regression methods. We recommend GLM models for this exercise. PMID- 27557996 TI - Virtue in Medical Practice: An Exploratory Study. AB - Virtue ethics has long provided fruitful resources for the study of issues in medical ethics. In particular, study of the moral virtues of the good doctor-like kindness, fairness and good judgement-have provided insights into the nature of medical professionalism and the ethical demands on the medical practitioner as a moral person. Today, a substantial literature exists exploring the virtues in medical practice and many commentators advocate an emphasis on the inculcation of the virtues of good medical practice in medical education and throughout the medical career. However, until very recently, no empirical studies have attempted to investigate which virtues, in particular, medical doctors and medical students tend to have or not to have, nor how these virtues influence how they think about or practise medicine. The question of what virtuous medical practice is, is vast and, as we have written elsewhere, the question of how to study doctors' moral character is fraught with difficulty. In this paper, we report the results of a first-of-a-kind study that attempted to explore these issues at three medical schools (and associated practice regions) in the United Kingdom. We identify which character traits are important in the good doctor in the opinion of medical students and doctors and identify which virtues they say of themselves they possess and do not possess. Moreover, we identify how thinking about the virtues contributes to doctors' and medical students' thinking about common moral dilemmas in medicine. In ending, we remark on the implications for medical education. PMID- 27557997 TI - Frequency of peri-implant diseases and associated factors. AB - OBJECTIVE: To evaluate the frequency of peri-implant diseases and factors associated with its occurrence. MATERIAL AND METHODS: One hundred and fifty-five patients with dental implants were evaluated in this cross-sectional study. Dental implants were clinically and radiographically evaluated to diagnose their peri-implant condition, according to Mombelli (Proceedings of the 3rd European Workshop on Periodontology, 1999, Quintessence, London). Associations between peri-implant diseases and independent variables (socioeconomic, demographic and periodontal characteristics) were evaluated through bivariate analysis with chi squared and Fisher's exact tests, as well as by multiple logistic regression. The significance level was set at 5%. RESULTS: The frequencies of the peri-implant diseases, mucositis and peri-implantitis, in individuals were 54% and 28% (CI, 95%), respectively. The sample was almost exclusively of patients with untreated periodontal disease (93%). Bivariate analysis showed that these peri-implant diseases were associated with male patients (prevalence ratio [PR], 3.38), medication use (PR, 2.94), systemic diseases (PR, 2.25), number of implants (PR, 2.53), visible plaque index (PR, 2.49) and gingival index (PR, 2.70). Multiple logistic regression analysis showed that medication use (prevalence ratio adjusted [PRadj], 1.23; 95% CI: 1.04-1.46; P = 0.017), having two or more implants (PRadj, 1.22; 95% CI: 1.02-1.46; P = 0.029) and gingival bleeding index > 10% (PRadj, 1.22; 95% CI: 1.03-1.44; P = 0.022) were associated with the presence of peri-implant disease. CONCLUSION: Peri-implant diseases were diagnosed in 54% of patients; gingival index of greater than 10%, having more than two implants and use of medication were associated with the frequency of peri-implant disease. PMID- 27557998 TI - Focus on co-management in geriatric fracture care. PMID- 27557999 TI - Allometric scaling of brain regions to intra-cranial volume: An epidemiological MRI study. AB - There is growing evidence that sub-structures of the brain scale allometrically to total brain size, that is, in a non-proportional and non-linear way. Here, scaling of different volumes of interest (VOI) to intra-cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community-based Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo-cortical white matter, neo-cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age-associated atrophy, sex, ethnicity, or a systematic bias from study specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp 38:151-164, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27558001 TI - A Novel Flexible Ureteroscopy with Intelligent Control of Renal Pelvic Pressure: An Initial Experience of 93 Cases. AB - BACKGROUND: Flexible ureteroscopic lithotripsy (URS) is rapidly becoming a first line therapy for patients with renal and ureteral calculi. Most current medical infusion devices can only monitor infusion flow and pressure, but not renal pelvic pressure (RPP). PATIENTS AND METHODS: We designed a patented intelligent system to facilitate flexible URS that included an irrigation and suctioning platform and a ureteral access sheath (UAS) with a pressure-sensitive tip, enabling regulation of the infusion flow precisely and control of the vacuum suctioning by computerized real-time recording and monitoring of RPP. A stable RPP was ensured by pressure feedback technology. Ninety-three patients with renal or ureteral calculi participated in the study and received flexible URS. Gravel particles were sucked out automatically during the flexible URS. Patients were evaluated on postoperative days 1 and 30 by X-ray of kidneys, ureters, and bladder to assess stone-free status. RESULTS: In 81 of the 93 patients, only one surgery was needed to remove the stone. There were nine cases who failed the first surgery due to difficulty in placing the UAS, but flexible URS was performed in these patients after indwelling a Double-J stent to the ureter with the calculus for 2 weeks. Three cases were converted to percutaneous nephrolithotomy due to significant ureteral stenosis. For the 90 patients who underwent flexible URS, the actual RPP was controlled under 20 mmHg with clear operative visualization. The stone-free rates at postoperative days 1 and 30 were 90.0% (81/90) and 95.6% (86/90), respectively. Clavien I complications were noted in 13 cases, while Clavien II complications were noted in two cases. No major complications (Clavien III-V) were noted. CONCLUSIONS: Our patented system is technically feasible, safe, and efficient for treating upper urinary calculi. The advantages include breaking stones effectively and low complication rates because of its automatic control of RPP. PMID- 27558000 TI - Antibody responses to Plasmodium falciparum and Plasmodium vivax blood-stage and sporozoite antigens in the postpartum period. AB - During pregnancy a variety of immunological changes occur to accommodate the fetus. It is unknown whether these changes continue to affect humoral immunity postpartum or how quickly they resolve. IgG levels were measured to P. falciparum and P. vivax antigens in 201 postpartum and 201 controls over 12 weeks. Linear mixed-effects models assessed antibody maintenance over time and the effect of microscopically confirmed Plasmodium spp. infection on antibody levels, and whether this was different in postpartum women compared with control women. Postpartum women had reduced Plasmodium spp. antibody levels compared to controls at baseline. Over 12 weeks, mean antibody levels in postpartum women increased to levels observed in control women. Microscopically confirmed P. falciparum and P. vivax infections during follow-up were associated with an increase in species specific antibodies with similar magnitudes of boosting observed in postpartum and control women. Antibodies specific for pregnancy-associated, VAR2CSA expressing parasites did not rapidly decline postpartum and did not boost in response to infection in either postpartum or control women. After pregnancy, levels of malaria-specific antibodies were reduced, but recovered to levels seen in control women. There was no evidence of an impaired ability to mount a boosting response in postpartum women. PMID- 27558002 TI - Evaluation of the vascular protective effects of new oral anticoagulants in high risk patients with atrial fibrillation (PREFER-AF): study protocol for a randomized controlled trial. AB - BACKGROUND: Atrial fibrillation (AF) is known to be associated with several pathophysiological mechanisms including endothelial dysfunction of the heart and arterial vessels. Recent evidence suggests that new oral anticoagulant (NOAC) treatment may improve endothelial function and the inflammatory process involved in atherosclerosis in AF patients. This study is designed to determine the efficacy of NOAC therapy in the prevention of endothelial dysfunction and the progression of atherosclerosis of AF subjects. METHOD/DESIGN: AF patients with a CHA2DS2-VASc score >2 and no previous history of overt coronary disease, severe peripheral arterial disease (PAD) or major stroke will be registered and randomly assigned either to the NOAC group (dabigatran or rivaroxaban) or the warfarin group in this prospective, randomized, 2-year follow-up study. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function will be conducted using the Endo-PAT2000 device. Left and right carotid intima-media thickness (IMT) will be measured at baseline, 12 months, and 24 months. The primary endpoint is defined as change in Reactive Hyperemia Index (RHI) at 12 months. Secondary endpoints included changes in the right and left maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA), the mean IMT of the CCA and ICA at 24 months, and 24-month cardiovascular events including cardiac death, stroke, acute myocardial infarction (AMI), overall cause of death, withdrawal of drug, or bleeding events. DISCUSSION: This is the first study to evaluate the efficacy of NOAC therapy for the prevention of endothelial dysfunction and progression of atherosclerosis in AF subjects. These findings are expected to expand the knowledge of NOAC pleotropic action in AF patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02544932 , registered on 7 September 2015. PMID- 27558003 TI - Arterial access and arteriotomy site closure devices. AB - Arterial access and haemostasis are fundamental aspects of procedures performed in the cardiac catheterization laboratory. The first description of arterial access for cardiac catheterization was in 1948, when surgical cut-down was used to access the radial artery. Over the next 2 decades, the preferred arteriotomy method transitioned from the Sones approach of brachial artery cut-down to the Seldinger and Judkins technique of percutaneous femoral artery access. Compared with the femoral approach, percutaneous transradial access results in reduced access-site bleeding, faster time to ambulation, and greater patient comfort. Several large-scale, randomized trials have also reported a survival advantage in patients with acute coronary syndromes treated with radial compared with femoral access. However, inconsistencies exist between the completed trials, and the underlying mechanism of a reduction in mortality with radial access is uncertain. Femoral artery haemostasis can be achieved with either manual compression or vascular closure devices, with recent studies suggesting improved outcomes with the use of active closure systems. Radial artery haemostasis is achieved through the use of wristbands that mimic manual compression, and 'non-occlusive' haemostasis reduces the risk of radial artery occlusion. Newer arterial access routes and closure approaches for large-bore devices are being actively investigated. Expertise in both femoral and radial artery access and intervention is essential for contemporary interventional cardiologists. PMID- 27558004 TI - Interventional cardiology: Preventing heart failure after STEMI with a cardiac matrix. PMID- 27558005 TI - Hypertension: Blood-pressure lowering in type 2 diabetes. PMID- 27558006 TI - Matrix Infrared Spectra and Quantum Chemical Calculations of Ti, Zr, and Hf Dihydride Phosphinidene and Arsinidene Molecules. AB - Laser ablated Ti, Zr, and Hf atoms react with phosphine during condensation in excess argon or neon at 4 K to form metal hydride insertion phosphides (H2P-MH) and metal dihydride phosphinidenes (HP?MH2) with metal phosphorus double bonds, which are characterized by their intense metal-hydride stretching frequencies. Both products are formed spontaneously on annealing the solid matrix samples, which suggests that both products are relaxed from the initial higher energy M PH3 intermediate complex, which is not observed. B3LYP (DFT) calculations show that these phosphinidenes are strongly agostic with acute H-P?M angles in the 60 degrees range, even smaller than those for the analogous methylidenes (carbenes) (CH2?MH2) and in contrast to the almost linear H-N?Ti subunit in the imines (H N?TiH2). Comparison of calculated agostic and terminal bond lengths and covalent bond radii for HP?TiH2 with computed bond lengths for Al2H6 finds that these strong agostic Ti-H bonds are 18% longer than single covalent bonds, and the bridged bonds in dialane are 10% longer than the terminal Al-H single bonds, which show that these agostic bonds can also be considered as bridged bonds. The analogous arsinidenes (HAs?MH2) have 4 degrees smaller agostic angles and almost the same metal-hydride stretching frequencies and double bond orders. Calculations with fixed H-P-Ti and H-As-Ti angles (170.0 degrees ) and Cs symmetry find that electronic energies increased by 36 and 44 kJ/mol, respectively, which provide estimates for the agostic/bridged bonding energies. PMID- 27558007 TI - Is body weight dissatisfaction a predictor of depression independent of body mass index, sex and age? Results of a cross-sectional study. AB - BACKGROUND: Little is known about the association of dissatisfaction with body weight - a component of body image - with depression in individuals of different sex, age, and with different body mass index (BMI). Hence, the aim of our study was to evaluate the association of body weight dissatisfaction (BWD) with depression in different sub-groups. METHODS: We analyzed data of 15,975 individuals from the cross-sectional 2012 Swiss Health Survey. Participants were asked about their body weight satisfaction. The validated Patient Health Questionnaire (PHQ-9) was used to ascertain depression. Age was stratified into three groups (18-29, 30-59, and >=60 years). The body mass index (BMI) was calculated from self-reported body height and weight and categorized into underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), and obesity (BMI >=30 kg/m(2)). The association between body weight dissatisfaction (BWD) and depression was assessed with logistic regression analyses and odds ratios (OR) with 95 % confidence intervals (CI) were computed. RESULTS: BWD was associated with depression in the overall group (OR 2.04, 95 % CI 1.66-2.50) as well as in men (OR 1.85, 95 % CI 1.34-2.56) and women (OR 2.25, 95 % CI 1.71-2.96) independent of BMI. The stratification by age groups showed significant associations of BWD with depression in young (OR 1.78, 95 % CI 1.16-2.74), middle-aged (OR 2.10, 95 % CI 1.61-2.74) and old individuals (OR 2.34, 95 % CI 1.30-4.23) independent of BMI. Stratification by BMI categories resulted in statistically significant positive associations of BWD and depression in underweight, normal weight, overweight and obese individuals. CONCLUSION: BWD was associated with depression independent of BMI, sex and age. PMID- 27558008 TI - Prevalence and Clinical Impact of Early Repolarization Pattern and QRS Fragmentation in High-Risk Patients With Brugada Syndrome. AB - BACKGROUND: The phenotypic heterogeneity of Brugada syndrome (BrS) can lead some patients to show an additional inferolateral early repolarization pattern (ERP), or fragmented QRS (f-QRS). The aim of the study was to investigate the prevalence and clinical impact of f-QRS, ERP or combined f-QRS/ERP in high-risk patients with BrS. METHODS AND RESULTS: Patients with spontaneous or drug-induced BrS and an indication to receive an implantable cardioverter-defibrillator (ICD) were considered eligible for this study. From 1992 to 2012, a total of 176 consecutive patients with BrS underwent ICD implantation. Among them, 48 subjects (27.3%) presented with additional depolarization and/or repolarization abnormalities. f QRS was found in 29 (16.5%), ERP in 15 (8.5%), and combined f-QRS/ERP in 4 patients (2.3%). After a mean follow-up of 95.2+/-51.9 months, spontaneous sustained ventricular arrhythmias were documented in 8 patients (16.7%). No significant difference was found in the rate of appropriate shocks between patients presenting with f-QRS or ERP and those without abnormalities. Patients with both f-QRS and ERP had a significantly higher rate of appropriate shocks (HR: 4.1; 95% CI: 1.1-19.7; P=0.04). CONCLUSIONS: Fragmented QRS and ERP are common ECG findings in high-risk BrS patients, occurring in up to 27% of cases. When combined, f-QRS and ERP confer a higher risk of appropriate ICD interventions during a very long-term follow-up. (Circ J 2016; 80: 2109-2116). PMID- 27558009 TI - Frobenius-norm-based measures of quantum coherence and asymmetry. AB - We formulate the Frobenius-norm-based measures for quantum coherence and asymmetry respectively. In contrast to the resource theory of coherence and asymmetry, we construct a natural measure of quantum coherence inspired from optical coherence theory while the group theoretical approach is employed to quantify the asymmetry of quantum states. Besides their simple structures and explicit physical meanings, we observe that these quantities are intimately related to the purity (or linear entropy) of the corresponding quantum states. Remarkably, we demonstrate that the proposed coherence quantifier is not only a measure of mixedness, but also an intrinsic (basis-independent) quantification of quantum coherence contained in quantum states, which can also be viewed as a normalized version of Brukner-Zeilinger invariant information. In our context, the asymmetry of N-qubit quantum systems is considered under local independent and collective transformations. In- triguingly, it is illustrated that the collective effect has a significant impact on the asymmetry measure, and quantum correlation between subsystems plays a non-negligible role in this circumstance. PMID- 27558010 TI - Biofilm may not be Necessary for the Epidemic Spread of Acinetobacter baumannii. AB - Biofilm is recognized as a contributing factor to the capacity of Acinetobacter baumannii to persist and prosper in medical settings, but it is still unknown whether biofilms contribute to the spread of A. baumannii. In this study, the biofilm formation of 114 clinical A. baumannii isolates and 32 non-baumannii Acinetobacter isolates was investigated using a microtiter plate assay. The clonal relationships among A. baumannii isolates were assessed using pulsed-field gel electrophoresis and multilocus sequence typing, and one major outbreak clone and 5 other epidemic clones were identified. Compared with the epidemic or outbreak A. baumannii isolates, the sporadic isolates had significantly higher biofilm formation, but no significant difference was observed between the sporadic A. baumannii isolates and the non-baumannii Acinetobacter isolates, suggesting that biofilm is not important for the epidemic spread of A. baumannii. Of the multidrug-resistant (MDR) A. baumannii isolates in this study, 95.7% were assigned to international clone 2 (IC2) and showed significantly lower biofilm formations than the other isolates, suggesting that biofilm did not contribute to the high success of IC2. These findings have increased our understanding of the potential relationship between biofilm formation and the epidemic capacity of A. baumannii. PMID- 27558011 TI - Mapping concentrations of posttraumatic stress and depression trajectories following Hurricane Ike. AB - We investigated geographic concentration in elevated risk for a range of postdisaster trajectories of chronic posttraumatic stress symptom (PTSS) and depression symptoms in a longitudinal study (N = 561) of a Hurricane Ike affected population in Galveston and Chambers counties, TX. Using an unadjusted spatial scan statistic, we detected clusters of elevated risk of PTSS trajectories, but not depression trajectories, on Galveston Island. We then tested for predictors of membership in each trajectory of PTSS and depression (e.g., demographic variables, trauma exposure, social support), not taking the geographic nature of the data into account. After adjusting for significant predictors in the spatial scan statistic, we noted that spatial clusters of PTSS persisted and additional clusters of depression trajectories emerged. This is the first study to show that longitudinal trajectories of postdisaster mental health problems may vary depending on the geographic location and the individual- and community-level factors present at these locations. Such knowledge is crucial to identifying vulnerable regions and populations within them, to provide guidance for early responders, and to mitigate mental health consequences through early detection of mental health needs in the population. As human-made disasters increase, our approach may be useful also in other regions in comparable settings worldwide. PMID- 27558012 TI - A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy. AB - BACKGROUND: Traditional Chinese medicine (TCM) has been widely used in treating various diseases in eastern Asia for several thousand years, and is becoming increasingly popular in western countries. Gubentongluo (GBTL) decoction, as a classic TCM formula, is commonly applied to treat IgA Nephropathy (IgAN) in China. To date, however, the pharmacological/molecular mechanisms of GBTL have not been fully elucidated. METHOD: In the present study, we used a system biological approach to explore these mechanisms acting on IgAN. RESULTS: First, we found 3876 potential target proteins for GBTL (based on TCMID) and 25 known IgAN associated biomarkers (based on the OMIM or IPA database).16 of the latter biomarkers were direct targets of 6 of the 9 herbs in GBTL, suggesting that these components play a vital role in treating IgAN. Second, we showed that these 6 herbs mainly regulate the immune system and renin-angiotensin system, imbalance in which is the main factor leading to IgAN. Importantly, HUANG QI links with 14 biomarkers, indicating that it is the most important herb in GBTL for treating IgAN. Also, relationships of other herbs with IgAN were explored. Third, we demonstrated that the remaining 9 IgAN associated proteins are responses to biological processes, such as antigen processing, protein ubiquitination and cell cycle regulation, which are crucial for IgAN development. Finally, we found that GBTL could induce a significant increase in the levels of two target gene: TNF and NOS2. CONCLUSIONS: Further studies are called to develop/modify the formula of GBTL, in order to enhance its effect on IgAN. PMID- 27558013 TI - HLA class I variation in Iranian Lur and Kurd populations: high haplotype and allotype diversity with an abundance of KIR ligands. AB - HLA-A, -B and -C alleles of 285 individuals, representing three Iranian Lur populations and one Iranian Kurd population were sequenced completely, yielding human leukocyte antigen (HLA) class I genotypes at high resolution and filling four fields of the official HLA nomenclature. Each population has 87-99 alleles, evenly distributed between the three HLA class I genes, 145 alleles being identified in total. These alleles were already known, named and deposited in the HLA database. The alleles form 316 different HLA A-B-C haplotypes, with each population having between 80 and 112 haplotypes. The four Iranian populations form a related group that is distinguished from other populations, including other Iranians. All four KIR ligands - the A3/11, Bw4, C1 and C2 epitopes - are well represented, particularly Bw4, which is carried by three high-frequency allotypes: HLA-A*24:02, HLA-A*32:01 and HLA-B*51:01. In the Lur and Kurd populations, between 82% and 94% of individuals have the Bw4 epitope, the ligand for KIR3DL1. HLA-B*51:01 is likely of Neandertal origin and associated with Behcet's disease, also known as the Silk Road disease. The Lordegan Lur have the highest frequency of HLA-B*51:01 in the world. This allele is present on 46 Lur and Kurd haplotypes. Present at lower frequency is HLA-B*51:08, which is also associated with Behcet's disease. In the four Iranian populations, 31 haplotypes encode both Bw4(+) HLA-A and Bw4(+) HLA-B, a dual combination of Bw4 epitopes that is relatively rare in other populations, worldwide. This study both demonstrates and emphasizes the value of studying HLA class I polymorphism at highest resolution in anthropologically well-defined populations. PMID- 27558014 TI - Human neutrophil elastase inhibitory potential of flavonoids from Campylotropis hirtella and their kinetics. AB - Campylotropis hirtella is used as a food supplement in the subtropical region of China. In an intensive hunt for human neutrophil elastase inhibitors, we isolated eight flavonoids from C. hirtella three of which (1-3) emerged to be elastase inhibitors. Geranylated flavonoids (1-3) displayed significant inhibitory activity with IC50s between 8.5 and 30.8 MUM. The most striking example was geranylated isofavanone 3 that inhibited elastase significantly (IC50 = 30.8 MUM) but its parent compound (dalbergioidin) and isoflavone analog (5) were inactive (IC50 > 200 MUM). Compounds (1-3) displayed different kinetic mechanisms (noncompetitive, competitive, and mixed type, respectively) that were dependent upon the parent skeleton. The competitive inhibitor, isoflavan-3-ol-4-one 2 manifested an inhibition of isomerization profile for elastase with kinetic parameters K5 = 0.0386 M-1S-1, K6 = 0.0244 MUM-1S-1 and Kiapp = 16.3427 MUM. The specific identification of metabolites was accomplished by LC-DAD-ESI/MS that was also used to analyze abundance of active components (1-3) within the plant. PMID- 27558015 TI - The Food and Drug Administration and varenicline: should risk communication be improved? PMID- 27558016 TI - Comb-referenced laser distance interferometer for industrial nanotechnology. AB - A prototype laser distance interferometer is demonstrated by incorporating the frequency comb of a femtosecond laser for mass-production of optoelectronic devices such as flat panel displays and solar cell devices. This comb-referenced interferometer uses four different wavelengths simultaneously to enable absolute distance measurement with the capability of comprehensive evaluation of the measurement stability and uncertainty. The measurement result reveals that the stability reaches 3.4 nm for a 3.8 m distance at 1.0 s averaging, which further reduces to 0.57 nm at 100 s averaging with a fractional stability of 1.5 * 10( 10). The uncertainty is estimated to be in a 10(-8) level when distance is measured in air due to the inevitable ambiguity in estimating the refractive index, but it can be enhanced to a 10(-10) level in vacuum. PMID- 27558017 TI - Protein Malnutrition Pre- and Postnatal and Nutritional Rehabilitation Modulates the Morphology of Muscle Fibers in Wistar Rats. AB - This study investigated the effects of pre- and postnatal conditions of protein deficiency followed to nutritional rehabilitation in the morphology of skeletal muscle. Twelve Wistar male rats were distributed in two groups: nourished (N), with normal protein diet and undernourished (U), with low protein diet. The respective diet was maintained until animals completed 21 days of life. After that, part of group U (n = 4) received normal protein diet, forming a third group, renourished group (R). Forty-two-day-old animals were euthanized and we performed histopathological and morphometric analysis of the soleus muscle. Analysis stained in hematoxylin and eosin (H&E) of the group N revealed polygonal and equidistant muscle fibers, with normal distribution in muscle fascicles. However, D group had rounded and disorganized fibers with different distances between them in muscle fascicles. R group presented muscle fibers with several formats, polygonal and rounded, and some muscle fascicles starting the reorganization process. In N group, analysis of the connective tissue showed predominance of type I collagen and a lower amount collagen type III, both well organized. Whereas U group had a predominance of disorganized type III collagen, in R group, there was return of type I collagen, but partially organized. Muscle fiber area of U (163.18 +/- 52.55 MUm2) and R (381.79 +/- 26.62 MUm2) groups was smaller than N (1229.2 MUm2 +/- 61.12 MUm2). Muscle fibers density of groups U (3369 +/- 1226 fibers/mm2) and R (1979 +/- 28 fibers/mm2) was larger than N (830 +/- 113 fibers/mm2). The nutritional rehabilitation in the present study showed an attempt of reorganization of the muscle tissue. PMID- 27558018 TI - Angiogenic inhibitors delivered by the type III secretion system of tumor targeting Salmonella typhimurium safely shrink tumors in mice. AB - Despite of a growing number of bacterial species that apparently exhibit intrinsic tumor-targeting properties, no bacterium is able to inhibit tumor growth completely in the immunocompetent hosts, due to its poor dissemination inside the tumors. Oxygen and inflammatory reaction form two barriers and restrain the spread of the bacteria inside the tumors. Here, we engineered a Salmonella typhimurium strain named ST8 which is safe and has limited ability to spread beyond the anaerobic regions of tumors. When injected systemically to tumor-bearing immunocompetent mice, ST8 accumulated in tumors at levels at least 100-fold greater than parental obligate anaerobic strain ST4. ST8/pSEndo harboring therapeutic plasmids encoding Endostatin fused with a secreted protein SopA could target vasculature at the tumor periphery, can stably maintain and safely deliver a therapeutic vector, release angiogenic inhibitors through a type III secretion system (T3SS) to interfere with the pro-angiogenic action of growth factors in tumors. Mice with murine CT26 colon cancer that had been injected with ST8/pSEndo showed efficient tumor suppression by inducing more severe necrosis and inhibiting blooding vessel density within tumors. Our findings provide a therapeutic platform for indirectly acting therapeutic strategies such as anti angiogenesis and immune therapy. PMID- 27558019 TI - Development of a novel strategy for fungal transformation based on a mutant locus conferring carboxin-resistance in Magnaporthe oryzae. AB - The accurate manipulation of genomic integration of mutant alleles or fluorescent fusion-protein constructs is necessary for understanding of pathogenic mechanism of Magnaporthe oryzae. Recently, this can be achieved by integrating of exogenous DNA randomly into genome of this pathogen, but ectopic integration may result in alteration of gene expression or gene disruption due to unpredictable position effects and/or disruption of protein-coding regions. In this study, we establish a novel strategy for locus-specific integration of exogenous DNA via carboxin resistance reconstitution by a point-mutation (H245L) on succinate dehydrogenase subunit Mosdi1. Independent transformants derived from the same reconstitution construct showed consistent fluorescent signal and undiversified phenotypes, including hyphae growth, conidiation and pathogenicity, in M. oryzae. Meanwhile, 96 % of all transformants integrate correctly into the Mosdi1 locus as a single copy. Furthermore, we provide a vector carrying yeast recombination cassette and thus allow assembly of multiple overlapping DNA fragments by yeast in vivo recombination for gene complementation and protein localization assay. PMID- 27558020 TI - Convergent evolutionary reduction of atrial septation in lungless salamanders. AB - Nearly two thirds of the approximately 700 species of living salamanders are lungless. These species respire entirely through the skin and buccopharyngeal mucosa. Lung loss dramatically impacts the configuration of the circulatory system but the effects of evolutionary lung loss on cardiac morphology have long been controversial. For example, there is presumably little need for an atrial septum in lungless salamanders due to the absence of pulmonary veins and the presence of a single source of mixed blood flowing into the heart, but whether lungless salamanders possess an atrial septum and whether the sinoatrial aperture is located in the left or right atrium are unresolved; authors have stated opposing claims since the late 1800s. Here, we use micro-computed tomography (MU CT) imaging, gross dissection and histological reconstruction to compare cardiac morphology among lungless plethodontid salamanders (Plethodontidae), salamanders with lungs, and the convergently lungless species Onychodactylus japonicus (Hynobiidae). Plethodontid salamanders have partial atrial septa and incomplete separation of the atrium into left and right halves. Partial septation is also seen in O. japonicus. Hence, lungless salamanders from two lineages convergently evolved similar morphology of the atrial septum. The partial septum in lungless salamanders can make it appear that the sinoatrial aperture is in the left atrium, but this interpretation is incorrect. Outgroup comparisons demonstrate that the aperture is located in a posterodorsal extension of the right atrium into the left side of the heart. Independent evolutionary losses of the atrial septum may have a similar developmental basis. In mammals, the lungs induce formation of the atrial septum by secreting morphogens to neighboring mesenchyme. We hypothesize that the lungs induce atrial septum development in amphibians in a similar fashion to mammals, and that atrial septum reduction in lungless salamanders is a direct result of lunglessness. PMID- 27558021 TI - Intermediate magnetization state and competing orders in Dy2Ti2O7 and Ho2Ti2O7. AB - Among the frustrated magnetic materials, spin-ice stands out as a particularly interesting system. Residual entropy, freezing and glassiness, Kasteleyn transitions and fractionalization of excitations in three dimensions all stem from a simple classical Hamiltonian. But is the usual spin-ice Hamiltonian a correct description of the experimental systems? Here we address this issue by measuring magnetic susceptibility in the two most studied spin-ice compounds, Dy2Ti2O7 and Ho2Ti2O7, using a vector magnet. Using these results, and guided by a theoretical analysis of possible distortions to the pyrochlore lattice, we construct an effective Hamiltonian and explore it using Monte Carlo simulations. We show how this Hamiltonian reproduces the experimental results, including the formation of a phase of intermediate polarization, and gives important information about the possible ground state of real spin-ice systems. Our work suggests an unusual situation in which distortions might contribute to the preservation rather than relief of the effects of frustration. PMID- 27558023 TI - Immunohistochemical staining for diagnosis of cutaneous mastocytosis. PMID- 27558022 TI - Establishing a tree shrew model of systemic lupus erythematosus and cell transplantation treatment. AB - BACKGROUND: The establishment of a tree shrew model for systemic lupus erythematosus (SLE) provides a new method to evaluate the pathogenesis of autoimmune diseases. METHODS: Eighty tree shrews were randomly divided into four groups receiving either an intraperitoneal injection of pristane, lipopolysaccharide (LPS), or pristane and LPS, or no injection. Three weeks after injection, the SLE model tree shrews were divided into the model group and the treatment group. Tree shrews in the treatment group and the normal control group were infused with umbilical cord mesenchymal stem cells (UC-MSCs). The cells were labeled with DiR. Two weeks after transplantation, three groups of tree shrews were analyzed for urine protein, serum antinuclear antibodies and antiphospholipid, and inflammatory cytokine antibody microarray detection. The heart, liver, spleen, lung, and kidney were collected from the three groups and subjected to hematoxylin and eosin (HE) staining and detection of renal immune complex deposition. RESULTS: HE staining indicated pathology in the model group. Red fluorescence revealed immune complex deposition in the kidneys from the model group. CONCLUSIONS: The combined intraperitoneal injection of pristane and LPS is the best way to induce SLE pathological changes. The pathological changes improved after UC-MSC treatment. PMID- 27558024 TI - Medication errors as malpractice-a qualitative content analysis of 585 medication errors by nurses in Sweden. AB - BACKGROUND: Many studies address the prevalence of medication errors but few address medication errors serious enough to be regarded as malpractice. Other studies have analyzed the individual and system contributory factor leading to a medication error. Nurses have a key role in medication administration, and there are contradictory reports on the nurses' work experience in relation to the risk and type for medication errors. METHODS: All medication errors where a nurse was held responsible for malpractice (n = 585) during 11 years in Sweden were included. A qualitative content analysis and classification according to the type and the individual and system contributory factors was made. In order to test for possible differences between nurses' work experience and associations within and between the errors and contributory factors, Fisher's exact test was used, and Cohen's kappa (k) was performed to estimate the magnitude and direction of the associations. RESULTS: There were a total of 613 medication errors in the 585 cases, the most common being "Wrong dose" (41 %), "Wrong patient" (13 %) and "Omission of drug" (12 %). In 95 % of the cases, an average of 1.4 individual contributory factors was found; the most common being "Negligence, forgetfulness or lack of attentiveness" (68 %), "Proper protocol not followed" (25 %), "Lack of knowledge" (13 %) and "Practice beyond scope" (12 %). In 78 % of the cases, an average of 1.7 system contributory factors was found; the most common being "Role overload" (36 %), "Unclear communication or orders" (30 %) and "Lack of adequate access to guidelines or unclear organisational routines" (30 %). The errors "Wrong patient due to mix-up of patients" and "Wrong route" and the contributory factors "Lack of knowledge" and "Negligence, forgetfulness or lack of attentiveness" were more common in less experienced nurses. The experienced nurses were more prone to "Practice beyond scope of practice" and to make errors in spite of "Lack of adequate access to guidelines or unclear organisational routines". CONCLUSIONS: Medication errors regarded as malpractice in Sweden were of the same character as medication errors worldwide. A complex interplay between individual and system factors often contributed to the errors. PMID- 27558025 TI - Polyurethane/Cotton/Carbon Nanotubes Core-Spun Yarn as High Reliability Stretchable Strain Sensor for Human Motion Detection. AB - Smart yarns and textiles are an active field of researches nowadays due to their potential applications in flexible and stretchable electronics, wearable devices, and electronic sensors. Integration of ordinary yarns with conductive fillers renders the composite yarns with new intriguing functions, such as sensation and monitoring of strain and stress. Here we report a low cost scalable fabrication for highly reliable, stretchable, and conductive composite yarn as effective strain sensing material for human motion monitoring. By incorporating highly conductive single-wall carbon nanotubes (SWCNTs) into the elastic cotton/polyurethane (PU) core-spun yarn through a self-designed coating approach, we demonstrated that the yarn is able to detect and monitor the movement of human limbs, such as finger and elbow, and even the wink of eyes. By virtue of the covered structure of the cotton/PU yarn and the reinforcement effect of SWCNTs, the composite yarn can bear up to 300% strain and could be cycled nearly 300,000 times under 40% strain without noticeable breakage. It is promising that this kind of conductive yarn can be integrated into various fabrics and used in future wearable devices and electronic skins. PMID- 27558026 TI - Clinical and pathological analysis of IgA nephropathy with chronic renal failure. AB - OBJECTIVE: To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. METHOD: Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. RESULTS: Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 +/- 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p < 0.05, respectively). The most common pathological type was proliferative sclerosis glomerulonephritis (PSGN) and M1S1E0T0 according to WHO definition and Oxford Classification, respectively, and most of the 65 cases had glomerulosclerosis. Simple IgA deposition was the most common immunopathologic type. Of all the cases, 44.6% accompanied with C3 while 4.6% with C1q. Further analysis revealed there were no relationships between severity of pathological lesion and levels of clinical indexes (Scr and eGRF) (p > 0.05). CONCLUSION: IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them. PMID- 27558028 TI - Go forth and replicate! PMID- 27558027 TI - Harmonizing Global Biospecimen Consent Practices to Advance Translational Research: A Call to Action. AB - One of the many challenges of translational medicine is working with research participants to donate biospecimens through an ethical informed consent framework. The increasingly complex ethical and regulatory differences across jurisdictions translates into limitations on use and potential value of biological specimens and their associated data in clinical research. We introduce a call to action for more uniform global standards for collection of biological specimen informed consent data to enable greater advancements in medical research. PMID- 27558029 TI - China's soil plan needs strong support. PMID- 27558041 TI - Earth-sized planet around nearby star is astronomy dream come true. PMID- 27558042 TI - US personalized-medicine industry takes hit from Supreme Court. PMID- 27558043 TI - China, Japan, CERN: Who will host the next LHC? PMID- 27558044 TI - Obama's science legacy: betting big on biomedical science. PMID- 27558046 TI - Obama's science legacy: uneven progress on scientific integrity. PMID- 27558045 TI - Obama's science legacy: a space race stalls. PMID- 27558047 TI - Obama's science legacy: climate (policy) hots up. PMID- 27558048 TI - Busting the billion-dollar myth: how to slash the cost of drug development. PMID- 27558049 TI - Expand the frontiers of urban sustainability. PMID- 27558052 TI - Disaster risk: Strengthen China's flood control. PMID- 27558053 TI - Economy crisis: Venezuela's brain drain is accelerating. PMID- 27558054 TI - Conservation: Don't let climate crush coral efforts. PMID- 27558055 TI - Medical disorders: Stop marginalizing rare syndromes. PMID- 27558056 TI - Water management: Social changes affect water quality too. PMID- 27558057 TI - Alfred G. Knudson (1922-2016). PMID- 27558058 TI - Robotics: Generation soft. PMID- 27558059 TI - Inorganic chemistry: Fleeting glimpse of an elusive element. PMID- 27558060 TI - Neuroscience: Memories linked within a window of time. PMID- 27558062 TI - Astronomy: Earth-like planet around Sun's neighbour. PMID- 27558063 TI - Early onset of industrial-era warming across the oceans and continents. AB - The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-ad 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account. PMID- 27558064 TI - A terrestrial planet candidate in a temperate orbit around Proxima Centauri. AB - At a distance of 1.295 parsecs, the red dwarf Proxima Centauri (alpha Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref. 3) and its quiescent activity levels and X ray luminosity are comparable to those of the Sun. Here we report observations that reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major axis distance of around 0.05 astronomical units. Its equilibrium temperature is within the range where water could be liquid on its surface. PMID- 27558065 TI - An integrated design and fabrication strategy for entirely soft, autonomous robots. AB - Soft robots possess many attributes that are difficult, if not impossible, to achieve with conventional robots composed of rigid materials. Yet, despite recent advances, soft robots must still be tethered to hard robotic control systems and power sources. New strategies for creating completely soft robots, including soft analogues of these crucial components, are needed to realize their full potential. Here we report the untethered operation of a robot composed solely of soft materials. The robot is controlled with microfluidic logic that autonomously regulates fluid flow and, hence, catalytic decomposition of an on-board monopropellant fuel supply. Gas generated from the fuel decomposition inflates fluidic networks downstream of the reaction sites, resulting in actuation. The body and microfluidic logic of the robot are fabricated using moulding and soft lithography, respectively, and the pneumatic actuator networks, on-board fuel reservoirs and catalytic reaction chambers needed for movement are patterned within the body via a multi-material, embedded 3D printing technique. The fluidic and elastomeric architectures required for function span several orders of magnitude from the microscale to the macroscale. Our integrated design and rapid fabrication approach enables the programmable assembly of multiple materials within this architecture, laying the foundation for completely soft, autonomous robots. PMID- 27558067 TI - Isotopic composition of plant water sources. PMID- 27558069 TI - Response of diatom-associated bacteria to host growth state, nutrient concentrations, and viral host infection in a model system. AB - Diatoms are photosynthetic unicellular eukaryotes found ubiquitously in aquatic systems. Frequent physical associations with other microorganisms such as bacteria may influence diatom fitness. The predictability of bacterial-diatom interactions is hypothesized to depend on availability of nutrients as well as the physiological state of the host. Biotic and abiotic factors such as nutrient levels, host growth stage and host viral infection were manipulated to determine their effect on the ecological succession of bacterial communities associated with a single cell line of Chaetoceros sp. KBDT20; this was assessed using the relative abundance of bacterial phylotypes based on 16S rDNA sequences. A single bacterial family, Alteromonadaceae, dominated the attached-bacterial community (84.0%), with the most prevalent phylotypes belonging to the Alteromonas and Marinobacter genera. The taxa comprising the other 16% of the attached bacterial assemblage include Alphaproteobacteria, Betaproteobacteria, Bacilli, Deltaproteobacteria, other Gammaproteobacteria and Flavobacteria. Nutrient concentration and host growth stage had a statistically significant effect on the phylogenetic composition of the attached bacteria. It was inferred that interactions between attached bacteria, as well as the inherent stochasticity mediating contact may also contribute to diatom-bacterial associations. PMID- 27558068 TI - Evaristo et al. reply. PMID- 27558070 TI - Can myometrial elasticity, as determined by elastography at 18-22 weeks of gestation, predict preterm delivery? PMID- 27558071 TI - The Male Abnormal Gene Family 21 (Mab21) Members Regulate Eye Development. AB - The male abnormal gene family contains 3 members, named mab21l1, mab21l2 and mab21l3. Since their first discovery in C. elegans, homologues of mab21l1 and mab21l2 have been found in Drosophila, Zebrafish, Xenopus, chicken, mouse and human. A number of studies have revealed that mab21 gene family members, mab21l1 and mab21l2, play important roles in regulating eye development. Here, we review the functions of the mab genes in regulating ocular development. PMID- 27558073 TI - Toward the Development of a Fundamentally Based Chemical Model for Cyclopentanone: High-Pressure-Limit Rate Constants for H Atom Abstraction and Fuel Radical Decomposition. AB - Theoretical aspects of the development of a chemical kinetic model for the pyrolysis and combustion of a cyclic ketone, cyclopentanone, are considered. Calculated thermodynamic and kinetic data are presented for the first time for the principal species including 2- and 3-oxo-cyclopentyl radicals, which are in reasonable agreement with the literature. These radicals can be formed via H atom abstraction reactions by H and O atoms and OH, HO2, and CH3 radicals, the rate constants of which have been calculated. Abstraction from the beta-hydrogen atom is the dominant process when OH is involved, but the reverse holds true for HO2 radicals. The subsequent beta-scission of the radicals formed is also determined, and it is shown that recent tunable VUV photoionization mass spectrometry experiments can be interpreted in this light. The bulk of the calculations used the composite model chemistry G4, which was benchmarked in the simplest case with a coupled cluster treatment, CCSD(T), in the complete basis set limit. PMID- 27558072 TI - Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis. AB - BACKGROUND & AIMS: The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associations of ANCA in PSC. METHODS: Antineutrophil cytoplasmic antibodies were analysed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA-B and HLA-DRB1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA (pANCA) and HLA-DRB1 were available from 274 ulcerative colitis (UC) patients without known liver disease. RESULTS: Antineutrophil cytoplasmic antibodies were found in 193 (80%) of the PSC patients, with pANCA in 169 (70%). ANCA-positive patients were younger than ANCA negative at diagnosis of PSC and had a lower frequency of biliary cancer (9% vs 19%, P=.047). There were no differences between PSC patients with and without inflammatory bowel disease. Genetically, the strong PSC risk factors HLA-B*08 (frequency in healthy 13%) and DRB1*03 (14%) were more prevalent in ANCA-positive than -negative patients (43% vs 25%, P=.0012 and 43% vs 25%, P=.0015 respectively). The results were similar when restricting the analysis to pANCA-positive patients. In UC patients without liver disease, HLA-DRB1*03 was more prevalent in pANCA-positive compared with negative patients (P=.03). CONCLUSIONS: Antineutrophil cytoplasmic antibodies identified PSC patients with particular clinical and genetic characteristics, suggesting that ANCA may mark a clinically relevant pathogenetic subgroup in the PSC-UC disease spectrum. PMID- 27558074 TI - Study of differentiated human umbilical cord-derived mesenchymal stem cells transplantation on rat model of advanced parkinsonism. AB - The aim of this study was to explore the curative effect of differentiated human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation on rat of advanced Parkinson disease (PD) model. Human umbilical cord-derived mesenchymal stem cells were cultured and induced differentiation in vitro. The PD rats were established and allocated randomly into 2 groups: differentiated hUC MSCs groups and physiological saline groups (the control group). Rotation test and immunofluorescence double staining were done. The result showed that hUC-MSCs could differentiate into mature dopamine neurons. Frequency of rotation was significantly less in differentiated hUC-MSCs groups than in normal saline group. After we transplanted these cells into the unilateral lesioned substantia nigra induced by striatal injection of 6-hydroxydopamine and performed in the medial forebrain bundle and ventral tegmental area, nigral tyrosine hydroxylase-positive cells were observed and survival of at least 2 months. In addition, transplantation of hUC-MSCs could make an obviously therapeutic effect on PD rats. PMID- 27558075 TI - MicroRNA signatures predict dysregulated vitamin D receptor and calcium pathways status in limb girdle muscle dystrophies (LGMD) 2A/2B. AB - miRNA expression profile and predicted pathways involved in selected limb-girdle muscular dystrophy (LGMD)2A/2B patients were investigated. A total of 187 miRNAs were dysregulated in all patients, with six miRNAs showing opposite regulation in LGMD2A versus LGMD2B patients. Silico analysis evidence: (1) a cluster of the dysregulated miRNAs resulted primarily involved in inflammation and calcium metabolism, and (2) two genes predicted as controlled by calcium-assigned miRNAs (Vitamin D Receptor gene and Guanine Nucleotide Binding protein beta polypeptide 1gene) showed an evident upregulation in LGMD2B patients, in accordance with miRNA levels. Our data support alterations in calcium pathway status in LGMD 2A/B, suggesting myofibre calcium imbalance as a potential therapeutic target. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27558076 TI - The Ganglioside GM-1 Inhibits Bupivacaine-Induced Neurotoxicity in Mouse Neuroblastoma Neuro2a Cells. AB - OBJECTIVE: Studies indicate that bupivacaine-induced neurotoxicity results from apoptosis. Gangliosides have been shown to promote neuronal repair and recovery of neurological function after spinal cord injury. Previously, we confirmed that in vivo administration of the ganglioside GM-1 attenuated bupivacaine-induced neurotoxicity in various animal models; however, the underlying mechanism remains unclear. METHODS: Cells of the neuroblastoma line N2a (Neuro2a cells) were divided into three experimental groups: control, bupivacaine-treated, and bupivacaine-treated with GM-1 pretreatment. Cell viability and apoptosis were assessed through CCK-8 assays, Hoechst staining, and flow cytometry analysis of Annexin-V/propidium iodide double labeling. Real-time polymerase chain reaction and western blotting assessed the expression of caspase-3, caspase-8, and caspase 9. RESULTS: Bupivacaine-induced apoptosis worsened with increasing dose and exposure time. Bupivacaine induced increased expression of caspase-3 and caspase 9, but not caspase-8, indicating that the mitochondrial pathway but not the death receptor apoptosis pathway was activated. GM-1 pretreatment inhibited bupivacaine induced apoptosis and the expression of caspase-3 and caspase-9 in a dose dependent manner. CONCLUSION: Bupivacaine induced neurotoxicity by activating apoptosis via the mitochondrial pathway, and this was inhibited by GM-1 pretreatment. PMID- 27558077 TI - Increased healthcare resource utilization in higher disease activity levels in initiators of TNF inhibitors among US rheumatoid arthritis patients. AB - OBJECTIVE: Determine healthcare resource utilization (HCRU) in biologic-naive initiators of TNF inhibitors (TNFis) associated with their disease activity from a national cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were identified at their first TNFi initiation (index date) in the Corrona registry. Patients with age of RA onset <18, comorbid psoriasis/psoriatic arthritis, fibromyalgia, or osteoarthritis were excluded. Patients were categorized into disease activity (DA) strata by the lowest level of DA (and sustaining low levels for at least two visits) using the Clinical Disease Activity Index (CDAI) across all visits in Corrona while on a TNFi during 1 year after initiation. Rates of all-cause and RA-related hospitalizations, rheumatologist visits, and joint surgeries while on TNFi therapy were reported and compared across DA levels along with the incidence rate ratio (IRR) adjusted for age, gender, and RA duration using Poisson mixed models. RESULTS: Of 1931 RA patients: 15% achieved sustained remission, 22% remission, 14% sustained low DA, 23% low DA and 27% moderate/high DA (M/HDA). Those in M/HDA had statistically higher rates of hospitalizations (37.3 per 100 patient years (py), 95% CI: 31.6 43.7 and joint surgeries (20.8 per 100 py, 95% CI: 16.6-25.8) compared to the sustained remission cohort, resulting in respective IRRs of 2.3 (p < 0.001) and 1.7 (p = 0.046). CONCLUSION: Many biologic naive RA patients initiating TNFi failed to achieve sustained remission during a 1 year period while remaining on TNFi therapy. Patients in higher DA levels had higher HCRU rates vs. patients in sustained remission, suggesting that achieving treat-to-target goals would reduce health care expenses. PMID- 27558078 TI - Corrigendum: Exploration of acetanilide derivatives of 1-(omega phenoxyalkyl)uracils as novel inhibitors of Hepatitis C Virus replication. PMID- 27558079 TI - The synthesis of tritium, carbon-14 and stable isotope labelled selective estrogen receptor degraders. AB - As part of a Medicinal Chemistry program aimed at developing an orally bioavailable selective estrogen receptor degrader, a number of tritium, carbon 14, and stable isotope labelled (E)-3-[4-(2,3,4,9-tetrahydro-1H-pyrido[3,4 b]indol-1-yl)phenyl]prop-2-enoic acids were required. This paper discusses 5 synthetic approaches to this compound class. PMID- 27558080 TI - Blunted renal vasoconstriction in patients with subclinical contrast-induced renal injury. AB - Contrast media are considered to cause acute kidney injury by activating various factors that induce renal vasoconstriction. We analysed the renal microvascular haemodynamic response using the Doppler flow wire method. Then changes in urinary liver-type fatty acid-binding protein levels following contrast medium administration were compared between groups with or without a micro-injury of the kidney. In the group without renal micro-injury, the average peak velocity (APV) decreased significantly, whereas the renal artery resistance index (RI) increased significantly following contrast medium administration. In contrast, there was no significant change in either the APV or RI in the group with a renal micro injury. A blunted microvascular response was found in the micro-injury group, whereas microvascular resistance increased in the non-micro-injury group. PMID- 27558081 TI - Bilateral choroidal neovascularisation associated with adult-onset foveomacular vitelliform dystrophy. PMID- 27558082 TI - Durable clinical remission induced by romidepsin for chemotherapy-refractory peripheral T-cell lymphoma with central nervous system involvement. PMID- 27558083 TI - Commentary: Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio. PMID- 27558084 TI - Ruthenium(II)-Catalyzed C-H Activation of Imidamides and Divergent Couplings with Diazo Compounds: Substrate-Controlled Synthesis of Indoles and 3H-Indoles. AB - Indoles are an important structural motif that is commonly found in biologically active molecules. In this work, conditions for divergent couplings between imidamides and acceptor-acceptor diazo compounds were developed that afforded NH indoles and 3H-indoles under ruthenium catalysis. The coupling of alpha diazoketoesters afforded NH indoles by cleavage of the C(N2 )-C(acyl) bond whereas alpha-diazomalonates gave 3H-indoles by C-N bond cleavage. This reaction constitutes the first intermolecular coupling of diazo substrates with arenes by ruthenium-catalyzed C-H activation. PMID- 27558085 TI - Proteomics of Physcomitrella patens protonemata subjected to treatment with 12 oxo-phytodienoic acid. AB - 12-Oxo-phytodienoic acid (OPDA) is induced by mechanical wounding and suppresses the growth of Physcomitrella patens; OPDA is considered as a signal compound in this moss species. In this study, a proteomic analysis of P. patens protonemata treated with OPDA was performed. The abundance levels of 41 proteins were significantly altered by OPDA, with decreased levels for 40 proteins. The proteins for which abundance decreased in response to OPDA at the protonema developmental stage were mainly involved in the metabolism of proteins and carbohydrates. The effects of inhibition on protein abundance are likely a major physiological function of OPDA in P. patens. OPDA also suppressed the expression of histones at the protein level and gene transcription level. Suppression of histone expression might be an OPDA-specific function in P. patens protonemata. In P. patens, a subset of the physiological responses caused by OPDA is shown to differ between protonema and gametophore developmental stages. PMID- 27558086 TI - Dual Enzyme-Triggered In Situ Crosslinkable Gelatin Hydrogels for Artificial Cellular Microenvironments. AB - Horseradish peroxidase (HRP) and hydrogen peroxide (H2 O2 )-mediated crosslinking reaction has become an attractive method to create in situ forming hydrogels. While the crosslinking system has been widely utilized, there are certain issues require improvement to extend their biomedical applications, including creation of stiff hydrogels without compromising cytocompatibility due to initially high concentrations of H2 O2 . A gelatin-based hydrogels formed through a dual enzyme mediated crosslinking reaction using HRP and glucose oxidase (GOx) as an H2 O2 generating enzyme to gradually supply a radical source in HRP-mediated crosslinking reaction is reported. The physicochemical properties can be controlled by varying enzyme concentrations. Furthermore the hydrogel matrices provide 3D microenvironments for supporting the growth and spreading of human dermal fibroblasts with minimized cytotoxicity, despite the cells being encapsulated within stiff hydrogels. These hydrogels formed with HRP/GOx have great potential as artificial microenvironments for a wide range of biomedical applications. PMID- 27558087 TI - AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-kappaB and STAT3 Pathways. AB - Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1-7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1-7)/Mas and inhibiting the MAPK, NF-kappaB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1-7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases. PMID- 27558090 TI - Biomechanical Imaging Markers as Predictors of Abdominal Aortic Aneurysm Growth or Rupture: A Systematic Review. AB - OBJECTIVES: Biomechanical characteristics, such as wall stress, are important in the pathogenesis of abdominal aortic aneurysms (AAA) and can be visualised and quantified using imaging techniques. This systematic review aims to present an overview of all biomechanical imaging markers that have been studied in relation to AAA growth and rupture. METHODS: This systematic review followed the PRISMA guidelines. A search in Medline, Embase, and the Cochrane Library identified 1503 potentially relevant articles. Studies were included if they assessed biomechanical imaging markers and their potential association with growth or rupture. RESULTS: Twenty-seven articles comprising 1730 patients met the inclusion criteria. Eighteen studies performed wall stress analysis using finite element analysis (FEA), 13 of which used peak wall stress (PWS) to quantify wall stress. Ten of 13 case control FEA studies reported a significantly higher PWS for symptomatic or ruptured AAAs than for intact AAAs. However, in some studies there was confounding bias because of baseline differences in aneurysm diameter between groups. Clinical heterogeneity in methodology obstructed a meaningful meta-analysis of PWS. Three of five FEA studies reported a significant positive association between several wall stress markers, such as PWS and 99th percentile stress, and growth. One study reported a significant negative association and one other study reported no significant association. Studies assessing wall compliance, the augmentation index and wall stress analysis using Laplace's law, computational fluid dynamics and fluid structure interaction were also included in this systematic review. CONCLUSIONS: Although PWS is significantly higher in symptomatic or ruptured AAAs in most FEA studies, confounding bias, clinical heterogeneity, and lack of standardisation limit the interpretation and generalisability of the results. Also, there is conflicting evidence on whether increased wall stress is associated with growth. PMID- 27558091 TI - Treatment of a Type Ia Endoleak After EVAR and Iliac Branch Device with Partial Proximal Stentgraft Explantation and Dacron Graft Interposition. PMID- 27558088 TI - An RGS2 3'UTR polymorphism is associated with preeclampsia in overweight women. AB - BACKGROUND: Preeclampsia is a common and heterogeneous vascular syndrome of pregnancy. Its genetic risk profile is yet unknown and may vary between individuals and populations. The rs4606 3' UTR polymorphism of the Regulator of G protein signaling 2 gene (RGS2) in the mother has been implicated in preeclampsia as well as in the development of chronic hypertension after preeclampsia. The RGS2 protein acts as an inhibitor of physiological vasoconstrictive pathways, and a low RGS2 level is associated with hypertension and obesity, two conditions that predispose to preeclampsia. We genotyped the rs4606 polymorphism in 1339 preeclamptic patients and in 697 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort to study the association of the variant with preeclampsia. RESULTS: No association between rs4606 and preeclampsia was detected in the analysis including all women. However, the polymorphism was associated with preeclampsia in a subgroup of overweight women (body mass index >= 25 kg/m(2), and < 30 kg/m(2)) (dominant model; odds ratio, 1.64; 95 % confidence interval, 1.10-2.42). CONCLUSIONS: Our results suggest that RGS2 might be involved in the pathogenesis of preeclampsia particularly in overweight women and contribute to their increased risk for hypertension and other types of cardiovascular disease later in life. PMID- 27558092 TI - The destruction box is involved in the degradation of the NTE family proteins by the proteasome. AB - Neuropathy target esterase (NTE) and NTE-related esterase (NRE) are endoplasmic reticulum (ER) membrane-anchored proteins belonging to the NTE protein family. NTE and NRE are degraded by macroautophagy and by the ubiquitin-proteasome pathway. However, the regulation of NTE and NRE by proteasome has not been well understood. Western blotting showed that the deletion of the regulatory region of NTE and NRE led to protein accumulation compared with that of the corresponding wild-type proteins. Further, deletion and site-directed mutagenesis experiments demonstrated that the destruction (D) box was required for the proteasomal degradation of NTE and NRE. However, unlike the deletion of the regulatory region, the deletion of the D box did not affect the subcellular localisation of NTE or NRE or disrupt the ER. Moreover, the deletion of the D box or the regulatory region of NTE has similar inhibitory effects on cell growth, which are greater than those produced by the full-length NTE. Here, for the first time, we show that the D box is involved in the regulation of NTE family proteins by the proteasome but not in their subcellular localisation. In addition, these results suggest that the NTE overexpression-mediated inhibition of cell growth is related to active protein levels but not to its ER disruption effect. PMID- 27558094 TI - The cell fate: senescence or quiescence. AB - Senescence and quiescence are frequently used as interchangeable terms in the literature unwittingly. Despite the fact that common molecules play role in decision of cell cycle arrest, senescent and quiescent cells have some distinctive phenotypes at both molecular and morphological levels. Thus, in this review we summarized the features of senescence and quiescence with respect to visual characteristics and prominent key molecules. A PubMed research was conducted for the key words; "senescence", "quiescence" and "cell cycle arrest". The results which are related to cell cycle control were selected. The selection criteria of the target articles used for this review included also key cell cycle molecules such as p53, pRB, p21, p16, mTOR, p27, etc. The results were not evaluated statistically. The mechanistic target of rapamycin (mTOR) has been claimed to be key molecule in switching on/off senescence/quiescence. Specifically, although maximal p53 activation blocks mTOR and causes quiescence, partial p53 activation sustains mTOR activity and causes senescence subsequently. In broader perspective, quiescence occurs due to lack of nutrition and growth factors whereas senescence takes place due to aging and serious DNA damages. Contrary to quiescence, senescence is a degenerative process ensuing a certain cell death. We highlighted several differences between senescence and quiescence and their key molecules in this review. Whereas quiescence (cell cycle arrest) is only one half of the senescence, the other half is growth stimulation which causes actual senescence phenotype. PMID- 27558095 TI - Novel FBN1 mutations are responsible for cardiovascular manifestations of Marfan syndrome. AB - The fibrillin-1 (FBN1) gene mutations result in Marfan syndrome (MFS) and have a variety of phenotypic variations. This disease is involved in the skeletal, ocular and cardiovascular system. Here we analyzed genotype-phenotype correlation in two Chinese families with MFS. Two patients with thoracic aortic aneurysms and dissections were diagnosed as MFS according to the revised Ghent criteria. Peripheral blood samples were collected and genomic DNAs were isolated from available cases, namely, patient-1 and his daughter and son, and patient-2 and his parents. According to the next-generation sequencing results, the mutations in FBN1 were confirmed by direct sequencing. A heterozygous frameshift mutation in exon 12 of FBN1 was found in the proband-1 and his daughter. They showed cardiovascular phenotype thoracic aortic aneurysms and dissections, a life threatening vascular disease, and atrial septal defect respectively. One de novo missense mutation in exon 50 of FBN1 was identified only in the patient-2, showing aortic root aneurysm and aortic root dilatation. Intriguingly, two novel mutations mainly caused the cardiovascular complications in affected family members. No meaningful mutations were found in these two patients by screening all exons of 428 genes related with cardiovascular disease. The high incidence of cardiovascular manifestations might be associated with the two novel mutations in exon 12 and 50 of FBN1. PMID- 27558093 TI - Genome-wide identification of salinity responsive HSP70s in common bean. AB - The present study is aimed to identify and characterize HSP70 (PvHSP70) genes in two different common bean cultivars under salt stress. For this purpose various in silico methods such as RNAseq data and qRT-PCR analysis were used. A total of 24 candidate PvHSP70 gene were identified. Except for chromosome 4 and 7, these candidate PvHSP70 genes were distributed on the remaining chromosomes. While the lowest number of PvHSP70 genes was determined on chromosomes 1, 3, 5, 7, 9, 10 and 11 (one HSP70 gene), the highest number of PvHSP70s was on chromosomes 6 and 8 (seven HSP70 genes each). Three genes; PvHSP70-5, -9, and -10 were found to have no-introns. In addition, four tandemly and six segmentally duplicated gene couples were detected. A total of 13 PvHSP70 genes were targeted by miRNAs of 44 plant species and the most targeted genes were PvHSP70-5 and -23. The expression profile of PvHSP70 genes based on publicly available RNA-seq data was identified and salt treated leaf tissue was found to have more gene expression levels compared to the root. qRT-PCR analysis showed that the transcript concentrations of upregulated PvHSP70 genes in leaves of Zulbiye (sensitive) were mostly higher than those of Yakutiye (resistant). The present study revealed that PvHSP70 genes might play an important role in salt stress response for common bean cultivars and variability between cultivars also suggests that these genes could be used as functional markers for salt tolerance in common bean. PMID- 27558096 TI - Circadian Clocks in Articular Cartilage and Bone: A Compass in the Sea of Matrices. AB - Temporally coordinated resorption and synthesis is the key to maintaining healthy bones. Articular cartilage is a highly specialized connective tissue within the joints that lines the surface of a long bone. Emerging evidence has suggested a critical role of the circadian system in controlling cartilage and bone biology. Articular cartilage is sparsely populated with chondrocytes, surrounded by abundant extracellular matrices that are synthesized and maintained solely by chondrocytes. Once damaged, the articular cartilage tissue has poor capacity for endogenous repair, leaving the joints prone to osteoarthritis, an age-related painful condition that affects millions of individuals worldwide. An important question is how articular cartilage has evolved its remarkable capacity to maintain homeostasis and withstand daily biomechanical challenges associated with resting/activity cycles. Equally important is how this avascular and aneural tissue senses time and uses this information to coordinate daily phases of metabolic activity and tissue remodeling/repair. Bone tissue derived from cartilage has similarly sparse populations of resident cells living in dense and largely mineralized matrices. We discuss recent progress on circadian clocks in these matrix-rich skeletal tissues and highlight avenues for future research. PMID- 27558097 TI - A longitudinal, qualitative study exploring sustained adherence to a hand exercise programme for rheumatoid arthritis evaluated in the SARAH trial. AB - PURPOSE: This study explores the experience of participants taking part in a hand exercise programme for people with rheumatoid arthritis with a focus on adherence. The exercise programme was tested in a randomised controlled trial. This parallel qualitative study will inform future implementation into clinical practice. METHOD: Twenty-seven semi-structured interviews from 14 participants were undertaken at two time points (4 and 12 months after randomisation). We collected data of participants' experiences over time. This was guided by an interview schedule. Interview data were analysed using interpretative phenomenological analysis which is informed by phenomenological and hermeneutic theory. We recruited participants from National Health Service rheumatology and therapy departments. RESULTS: At 4 months, 11/14 participants reported continuing with the exercises. By 12 months, 7/13 participants still reported exercising. The ability to establish a routine determined whether participants adhered to the exercise programme. This was sometimes influenced by practical issues. We also identified facilitators and barriers to regular exercise in the themes of the following: the therapeutic encounter, perceived benefit of exercises, attitude of mind, confidence, and unpredictability. CONCLUSIONS: Establishing a routine was an important step towards participants being able to exercise independently. Therapists provided participants with skills to continue to exercise while dealing with changes in symptoms and schedules. Potential barriers to long-term exercise adherence need to be taken into account and addressed for successful implementation of this programme. Implications for Rehabilitation Behavioural change components such as the use of an exercise planner (stating intentions of where, when and how), daily diary sheets, and joint goal setting enhance adherence to a hand exercise programme for RA by helping to establish routines. Exercise routines need to be flexible enough to fit in with life and symptom changes whilst delivering a sufficient dosage. Therapists facilitate this process by using behavioural components alongside more commonly used aspects of care (assessment, education, advice, and encouragement) to enable people with RA to become independent exercisers. PMID- 27558098 TI - Mitigation of Initial Cardiodynamic Effects of the S1P1 Receptor Modulator Ponesimod Using a Novel Up-Titration Regimen. AB - Ponesimod, a potent selective sphingosine-1-phosphate receptor 1 modulator, leads to a reduction in circulating total lymphocyte count and transient decreases in heart rate (HR). Based on a modeling and simulation approach, this study was conducted to investigate whether a gradual up-titration regimen may mitigate these cardiodynamic effects. In this double-blind, placebo-controlled, randomized, 2-way crossover study, 32 healthy participants (15 males) received placebo on day 1 followed by multiple-dose administration of either ponesimod or placebo (ratio 3:1). Ponesimod was administered alternately using regimen A (incremental dose increase from 2 to 20 mg in 9 steps) or B (10 mg for 7 days followed by a single-dose administration of 20 mg). Cardiodynamic (Holter and 12 lead ECG), pharmacokinetic, pharmacodynamic (total lymphocyte count), and safety variables were assessed. After first-dose ponesimod administration (day 2), a transient decrease in HR was observed (nadir 2-3 hours postdose, back to predose values within 4-5 hours) of approximately 6 and 12 beats/min (bpm) (mean) following regimens A and B, respectively. On day 2, occurrence of HR <45 bpm, HR decrease from baseline of over 20 bpm, PR interval >=200 milliseconds, or PR interval increase from baseline >20 ms, was lower following regimen A than B (14 vs 43 events). During the course of the study, incidence of HR <45 bpm was lower following regimen A than B (20 vs 58 events). Fewer participants reported adverse events following regimen A than B. Pharmacokinetics and pharmacodynamics were similar between the regimens. The novel gradual up-titration with ponesimod markedly mitigated initial cardiodynamic effects. PMID- 27558099 TI - Affinity capillary electrophoresis: the theory of electromigration. AB - We focus on the state-of-the-art theory of electromigration under single and multiple complexation equilibrium. Only 1:1 complexation stoichiometry is discussed because of its unique status in the field of affinity capillary electrophoresis (ACE). First, we summarize the formulas for the effective mobility in various ACE systems as they appeared since the pioneering days in 1992 up to the most recent theories till 2015. Disturbing phenomena that do not alter the mobility of the analyte directly but cause an unexpected peak broadening have been studied only recently and are also discussed in this paper. Second, we turn our attention to the viscosity effects in ACE. Change in the background electrolyte viscosity is unavoidable in ACE but numerous observations scattered throughout the literature have not been reviewed previously. This leads to an uncritical employment of correction factors that may or may not be appropriate in practice. Finally, we consider the ionic strength effects in ACE, too. Limitations of the current theories are also discussed and the tasks identified where open problems still prevail. Graphical Abstract A weak base (A) undergoes an acidic-basic equilibria (in blue) and migrates with an electrophoretic mobility of [Formula: see text]. Simultaneously, it interacts with a selector (sel) while the analyte-selector complex migrates with an electrophoretic mobility of [Formula: see text]. The strength of the interaction (in orange) is governed by the binding constant, K A , and the concentration of the selector, c sel . This all gives the analyte an effective mobility of [Formula: see text] and moves it out of the zero position (EOF; right top insert). The interaction of the positively charged analyte with the neutral selector slows down the analyte with increasing selector concentration (right bottom insert). PMID- 27558100 TI - Can cloud point-based enrichment, preservation, and detection methods help to bridge gaps in aquatic nanometrology? AB - Coacervate-based techniques are intensively used in environmental analytical chemistry to enrich and extract different kinds of analytes. Most methods focus on the total content or the speciation of inorganic and organic substances. Size fractionation is less commonly addressed. Within coacervate-based techniques, cloud point extraction (CPE) is characterized by a phase separation of non-ionic surfactants dispersed in an aqueous solution when the respective cloud point temperature is exceeded. In this context, the feature article raises the following question: May CPE in future studies serve as a key tool (i) to enrich and extract nanoparticles (NPs) from complex environmental matrices prior to analyses and (ii) to preserve the colloidal status of unstable environmental samples? With respect to engineered NPs, a significant gap between environmental concentrations and size- and element-specific analytical capabilities is still visible. CPE may support efforts to overcome this "concentration gap" via the analyte enrichment. In addition, most environmental colloidal systems are known to be unstable, dynamic, and sensitive to changes of the environmental conditions during sampling and sample preparation. This delivers a so far unsolved "sample preparation dilemma" in the analytical process. The authors are of the opinion that CPE-based methods have the potential to preserve the colloidal status of these instable samples. Focusing on NPs, this feature article aims to support the discussion on the creation of a convention called the "CPE extractable fraction" by connecting current knowledge on CPE mechanisms and on available applications, via the uncertainties visible and modeling approaches available, with potential future benefits from CPE protocols. PMID- 27558101 TI - Evaluation of the performance of quantitative detection of the Listeria monocytogenes prfA locus with droplet digital PCR. AB - Fast and reliable pathogen detection is an important issue for human health. Since conventional microbiological methods are rather slow, there is growing interest in detection and quantification using molecular methods. The droplet digital polymerase chain reaction (ddPCR) is a relatively new PCR method for absolute and accurate quantification without external standards. Using the Listeria monocytogenes specific prfA assay, we focused on the questions of whether the assay was directly transferable to ddPCR and whether ddPCR was suitable for samples derived from heterogeneous matrices, such as foodstuffs that often included inhibitors and a non-target bacterial background flora. Although the prfA assay showed suboptimal cluster formation, use of ddPCR for quantification of L. monocytogenes from pure bacterial cultures, artificially contaminated cheese, and naturally contaminated foodstuff was satisfactory over a relatively broad dynamic range. Moreover, results demonstrated the outstanding detection limit of one copy. However, while poorer DNA quality, such as resulting from longer storage, can impair ddPCR, internal amplification control (IAC) of prfA by ddPCR, that is integrated in the genome of L. monocytogenes DeltaprfA, showed even slightly better quantification over a broader dynamic range. Graphical Abstract Evaluating the absolute quantification potential of ddPCR targeting Listeria monocytogenes prfA. PMID- 27558102 TI - Revealing the composition of organic materials in polychrome works of art: the role of mass spectrometry-based techniques. AB - The most recent advances in the identification and determination of organic constituents in paintings and other polychrome objects using mass spectrometry (MS)-based techniques are reviewed. The latest achievements in gas chromatography (GC)-MS and pyrolysis (Py-) GC-MS are mainly related to sample pretreatment protocols and to the employment of double-shot or laser desorption pyrolysis, respectively. MS techniques based on soft ionization methods such as matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) are discussed. So far, MALDI and ESI MS have been mainly used in the characterization of proteinaceous materials, but further applications are definitely emerging, e.g., in the fields of lipids, resins, and organic colorants analysis. Chemical imaging by time-of-flight secondary ion mass spectrometry (TOF SIMS), formerly applied to the detection and localization of lipid binders and inorganic materials, has been recently extended to proteins. Finally, the potential of niche techniques such as direct temperature resolved mass spectrometry (DTMS) and direct analysis in real time (DART) MS are outlined. PMID- 27558103 TI - A novel solid-state electrochemiluminescence sensor for detection of cytochrome c based on ceria nanoparticles decorated with reduced graphene oxide nanocomposite. AB - A novel ultrasensitive sensing system for the rapid detection of cytochrome c (Cyt C) was developed on the basis of an electrochemiluminescence (ECL) method. A nanocomposite biosensor was made of reduced graphene oxide decorated with cerium oxide/tris(2,2-bipyridyl)ruthenium(II)/chitosan (CeO2NPs-RGO/ Ru(bpy)3 (2+)/CHIT) and used for this purpose. The ECL signal was produced by an electrochemical interaction between Ru(bpy)3 (2+) and tripropyl amine (TPA) on the surface of the electrode. Addition of Cyt C to the solution decreases the ECL signal due to its affinity for TPA and inhibition of its reaction with Ru(bpy)3 (2+). The effects of the amount of CeO2NPs-RGO, Ru(bpy)3 (2+), TPA concentration as a co-reactant, and the pH of the electrolyte solution on the ECL signal intensity were studied and optimized. The results showed that the method was fast, reproducible, sensitive, and stable for the detection of Cyt C. The method has a linear range from 2.5 nM to 2 MUM (R (2) = 0.995) with a detection limit of 0.7 nM. Finally, the proposed biosensor was used for the determination of Cyt C in human serum samples with RSDs of 1.8-3.6 %. The results demonstrate that this solid-state ECL quenching biosensor has high sensitivity, selectivity, and good stability. Graphical Abstract A novel solid-state electrochemiluminescence sensor for detection of cytochrome C based on Ceria Nanoparticles Decorated Reduced Graphene Oxide Nanocomposite. PMID- 27558104 TI - Wide-scope screening of pesticides in fruits and vegetables using information dependent acquisition employing UHPLC-QTOF-MS and automated MS/MS library searching. AB - This paper presents an application of ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) for simultaneous screening and identification of 427 pesticides in fresh fruit and vegetable samples. Both full MS scan mode for quantification, and an artificial intelligence-based product ion scan mode information-dependent acquisition (IDA) providing automatic MS to MS/MS switching of product ion spectra for identification, were conducted by one injection. A home-in collision-induced dissociation all product ions accurate mass spectra library containing more than 1700 spectra was developed prior to actual application. Both qualitative and quantitative validations of the method were carried out. The result showed that 97.4 % of the pesticides had the screening detection limit (SDL) less than 50 MUg kg-1 and more than 86.7 % could be confirmed by accurate MS/MS spectra embodied in the home-made library. Meanwhile, calibration curves covering two orders of magnitude were performed, and they were linear over the concentration range studied for the selected matrices (from 5 to 500 MUg kg-1 for most of the pesticides). Recoveries between 80 and 110 % in four matrices (apple, orange, tomato, and spinach) at two spiked levels, 10 and 100 MUg kg-1, was 88.7 or 86.8 %. Furthermore, the overall relative standard deviation (RSD, n = 12) for 94.3 % of the pesticides in 10 MUg kg-1 and 98.1 % of the pesticides in 100 MUg kg-1 spiked levels was less than 20 %. In order to validate the suitability for routine analysis, the method was applied to 448 fruit and vegetable samples purchased in different local markets. The results show 83.3 % of the analyzed samples have positive findings (higher than the limits of identification and quantification), and 412 commodity-pesticide combinations are identified in our scope. The approach proved to be a cost-effective, time-saving and powerful strategy for routine large-scope screening of pesticides. PMID- 27558105 TI - Understanding the experience of care managers and relationship with patient outcomes: the COMPASS initiative. AB - OBJECTIVE: To understand how care managers implemented COMPASS and if this was related to patient health outcomes. METHODS: A total of 96 COMPASS care managers were approached to participate in the online survey and 93 (97%) provided responses. Correlations were generated between key survey responses and the average number of care management contacts, patient depression, blood pressure and glycosylated hemoglobin outcomes. RESULTS: Patients of care managers who reported spending more time on COMPASS-related tasks had higher rates of depression improvement (r=0.34; P=.002) and remission (r=0.27; P=.02) as well as higher rates of blood pressure control (r=0.29; P=.03). CONCLUSIONS: To improve the effectiveness of care management in collaborative care models, particularly for patients with comorbid conditions and complex nonmedical needs, care managers need the support of social work and administrative support staff. Care managers for this patient population would also benefit from more intensive training in nonpharmacological depression treatment, such as motivational interviewing and behavioral activation. Additionally, systems support is needed such as education for primary care teams and psychiatry on the value of collaborative care models and integration of population management tools into electronic medical records. PMID- 27558106 TI - Impact of a national collaborative care initiative for patients with depression and diabetes or cardiovascular disease. AB - OBJECTIVE: The spread of evidence-based care is an important challenge in healthcare. We evaluated spread of an evidence-based large-scale multisite collaborative care model for patients with depression and diabetes and/or cardiovascular disease (COMPASS). METHODS: Primary care patients with depression and comorbid diabetes or cardiovascular disease were recruited. Collaborative care teams used care management tracking systems and systematic case reviews to track and intensify treatment for patients not improving. Targeted outcomes were depression remission and response (assessed with the Patient Health Questionnaire 9) and control of diabetes (assessed by HbA1c) and blood pressure. Patients and clinicians were surveyed about satisfaction with care. RESULTS: Eighteen care systems and 172 clinics enrolled 3609 patients across the US. Of those with uncontrolled disease at enrollment, 40% achieved depression remission or response, 23% glucose control and 58% blood pressure control during a mean follow up of 11 months. There were large variations in outcomes across medical groups. Patients and clinicians were satisfied with COMPASS care. CONCLUSIONS: COMPASS was successfully spread across diverse care systems and demonstrated improved outcomes for complex patients with previously uncontrolled chronic disease. Future large-scale implementation projects should create robust processes to identify and reduce expected variation in implementation to consistently provide improved care. PMID- 27558107 TI - The COMPASS initiative: description of a nationwide collaborative approach to the care of patients with depression and diabetes and/or cardiovascular disease. AB - OBJECTIVE: To describe a national effort to disseminate and implement an evidence based collaborative care management model for patients with both depression and poorly controlled diabetes and/or cardiovascular disease across multiple, real world diverse clinical practice sites. METHODS: Goals for the initiative were as follows: (1) to improve depression symptoms in 40% of patients, (2) to improve diabetes and hypertension control rates by 20%, (3) to increase provider satisfaction by 20%, (4) to improve patient satisfaction with their care by 20% and (5) to demonstrate cost savings. A Care Management Tracking System was used for collecting clinical care information to create performance measures for quality improvement while also assessing the overall accomplishment of these goals. RESULTS: The Care of Mental, Physical and Substance-use Syndromes (COMPASS) initiative spread an evidence-based collaborative care model among 18 medical groups and 172 clinics in eight states. We describe the initiative's evidence-base and methods for others to replicate our work. CONCLUSIONS: The COMPASS initiative demonstrated that a diverse set of health care systems and other organizations can work together to rapidly implement an evidence-based care model for complex, hard-to-reach patients. We present this model as an example of how the time gap between research and practice can be reduced on a large scale. PMID- 27558108 TI - The Role of Presenilin in Protein Trafficking and Degradation-Implications for Metal Homeostasis. AB - An imbalance in metal homeostasis is a prominent feature of Alzheimer's disease (AD). A wealth of evidence from independent studies over the past two and half decades has found changes to the distribution of brain iron, zinc, and copper in AD patients and animal models of the disease. Early research focused on the association of these metals with amyloid beta (Abeta), particularly extraneuronal Abeta plaque pathology. In contrast, there are numerous studies that have demonstrated a loss of iron-, zinc-, or copper-dependent cellular functions in AD animal and cell models, highlighting the importance of metal homeostasis in maintaining healthy brain function. Characterizing the molecular pathways that are impacted by iron, zinc, or copper will shed light on how these metals affect neuoroprotection, and conversely, neurodegeneration. Of particular interest is the role that the AD-associated presenilins have on protein trafficking and degradation, as metal homeostasis is dependent on the efficient trafficking and recycling of specific metal transporters. This review summarizes what is currently known about presenilin-dependent protein trafficking and the role of presenilin in protein turnover, particularly via the autophagy-lysosomal system. PMID- 27558109 TI - MicroRNA-206 Inhibited the Progression of Glioblastoma Through BCL-2. AB - Gliomas are the most common type of brain tumor and have a poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous, and non-coding RNAs that play crucial roles in cell proliferation, survival, and invasion. Deregulated expression of miR-206 has been investigated in many cancers. However, the role of miR-206 in glioblastoma is still unclear. In the present study, we found that the expression of miR-206 was decreased in cancer tissues compared with normal tissues. However, the expression level of BCL-2 was higher in cancer tissues than that in normal tissues (all p < 0.001). Statistically, the expression level of BCL-2 was inversely correlated with the miR-206. In addition, the overall survival of glioblastoma patients with lower miR-206 expression was significantly shorter than those with high miR-206 expression (p < 0.001). Besides, the expression of miR-206 was also decreased in U87 and U251 cells. In vitro assays showed that ectopic miR-206 expression affected the proliferation, cell cycle, and invasion in U87 and U251 cells. Importantly, we identified BCL-2 as a direct target of miR-206 in U87 and U251 cells using luciferase assay. Overexpression of BCL-2 partially attenuated the miR-206-mediated cell proliferation. In vivo, overexpression of miR-206 suppressed the progression of glioblastoma cells using mice xenograft model. In conclusion, this study suggested that miR-206 could act as a tumor suppressor gene through inhibiting BCL-2 in the development of glioblastoma. PMID- 27558110 TI - Rapid detection of AAC(6')-Ib-cr production using a MALDI-TOF MS strategy. AB - Plasmid-mediated quinolone resistance mechanisms have become increasingly prevalent among Enterobacteriaceae strains since the 1990s. Among these mechanisms, AAC(6')-Ib-cr is the most difficult to detect. Different detection methods have been developed, but they require expensive procedures such as Sanger sequencing, pyrosequencing, polymerase chain reaction (PCR) restriction, or the time-consuming phenotypic method of Wachino. In this study, we describe a simple matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method which can be easily implemented in clinical laboratories that use the MALDI-TOF technique for bacterial identification. We tested 113 strains of Enterobacteriaceae, of which 64 harbored the aac(6')-Ib-cr gene. We compared two MALDI-TOF strategies, which differed by their norfloxacin concentration (0.03 vs. 0.5 g/L), and the method of Wachino with the PCR and sequencing strategy used as the reference. The MALDI-TOF strategy, performed with 0.03 g/L norfloxacin, and the method of Wachino yielded the same high performances (Se = 98 %, Sp = 100 %), but the turnaround time of the MALDI-TOF strategy was faster (<5 h), simpler, and inexpensive (<1 Euro). Our study shows that the MALDI-TOF strategy has the potential to become a major method for the detection of many different enzymatic resistance mechanisms. PMID- 27558111 TI - The HMGB1 C-Terminal Tail Regulates DNA Bending. AB - High mobility group box protein 1 (HMGB1) is an architectural protein that facilitates the formation of protein-DNA assemblies involved in transcription, recombination, DNA repair, and chromatin remodeling. Important to its function is the ability of HMGB1 to bend DNA non-sequence specifically. HMGB1 contains two HMG boxes that bind and bend DNA (the A box and the B box) and a C-terminal acidic tail. We investigated how these domains contribute to DNA bending by HMGB1 using single-molecule fluorescence resonance energy transfer (FRET), which enabled us to resolve heterogeneous populations of bent and unbent DNA. We found that full-length (FL) HMGB1 bent DNA more than the individual A and B boxes. Removing the C-terminal tail resulted in a protein that bent DNA to a greater extent than the FL protein. These data suggest that the A and B boxes simultaneously bind DNA in the absence of the C-terminal tail, but the tail modulates DNA binding and bending by one of the HMG boxes in the FL protein. Indeed, a construct composed of the B box and the C-terminal tail only bent DNA at higher protein concentrations. Moreover, in the context of the FL protein, mutating the A box such that it could not bend DNA resulted in a protein that bent DNA similar to a single HMG box and only at higher protein concentrations. We propose a model in which the HMGB1 C-terminal tail serves as an intramolecular damper that modulates the interaction of the B box with DNA. PMID- 27558112 TI - A Small Number of Residues Can Determine if Linker Histones Are Bound On or Off Dyad in the Chromatosome. AB - Linker histones bind to the nucleosome and regulate the structure and function of chromatin. We have previously shown that the globular domains of chicken H5 and Drosophila H1 linker histones bind to the nucleosome with on- or off-dyad modes, respectively. To explore the determinant for the distinct binding modes, we investigated the binding of a mutant globular domain of H5 to the nucleosome. This mutant, termed GH5_pMut, includes substitutions of five globular domain residues of H5 with the corresponding residues in the globular domain of Drosophila H1. The residues at these five positions play important roles in nucleosome binding by either H5 or Drosophila H1. NMR and spin-labeling experiments showed that GH5_pMut bound to the nucleosome off the dyad. We further found that the nucleosome array condensed by either the GH5_pMut or the globular domain of Drosophila H1 displayed a similar sedimentation coefficient, whereas the same nucleosome array condensed by the wild-type globular domain of H5 showed a much larger sedimentation coefficient. Moreover, NMR and spin-labeling results from the study of the nucleosome in complex with the full-length human linker histone H1.0, whose globular domain shares high sequence conservation with the corresponding globular domain of H5, are consistent with an on-dyad binding mode. Taken together, our results suggest that a small number of residues in the globular domain of a linker histone can control its binding location on the nucleosome and higher-order chromatin structure. PMID- 27558114 TI - Early- and Mid-term Results of the Chimney Technique in the Repair of Aortic Arch Pathologies. AB - PURPOSE: To examine the safety, feasibility, and mid-term efficacy of the chimney technique for aortic arch pathologies. METHODS: From February 2011 to December 2014, a total of 35 patients (30 men; mean age 54.3 +/- 14.1 years) with aortic arch pathologies underwent thoracic endovascular aortic repair combined with chimney stents. The indication was a proximal landing zone <1.5 cm. Follow-up was performed at 3, 6, and 12 months and then yearly thereafter. RESULTS: A total of 36 chimney stents were deployed (innominate artery, n = 1; left common carotid artery, n = 9; right subclavian artery, n = 1; left subclavian artery, n = 25). The technical success rate was 94.3 % (33/35). Immediate type Ia endoleaks (ELIa) were observed in two patients (8.6 %, 2/35). Twenty-five patients were successfully followed-up for a median period of 29.3 months (range, 6-48 months). One patient died due to aortic dissection aneurysm rupture at 36 months (mortality rate of 4 %, 1/25). Three late ELIa were observed and no reinterventions were performed. The overall incidence of ELIa was 20 % (5/25). During follow-up, the patency rate for chimney stents was 92 % (23/25). CONCLUSION: Our limited experience demonstrates that the chimney technique is a viable and relatively safe treatment for patients with challenging thoracic aortic pathologies at least in the mid-term follow-up period. PMID- 27558113 TI - Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury. AB - BACKGROUND: The uses of engineered nanomaterials have expanded in biomedical technology and consumer manufacturing. Furthermore, pulmonary exposure to various engineered nanomaterials has, likewise, demonstrated the ability to exacerbate cardiac ischemia reperfusion (I/R) injury. However, the influence of particle size or capping agent remains unclear. In an effort to address these influences we explored response to 2 different size gold core nanosilver particles (AgNP) with two different capping agents at 2 different time points. We hypothesized that a pulmonary exposure to AgNP induces cardiovascular toxicity influenced by inflammation and vascular dysfunction resulting in expansion of cardiac I/R Injury that is sensitive to particle size and the capping agent. METHODS: Male Sprague-Dawley rats were exposed to 200 MUg of 20 or 110 nm polyvinylprryolidone (PVP) or citrate capped AgNP. One and 7 days following intratracheal instillation serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and isolated coronary artery and aorta segment were assessed for constrictor responses and endothelial dependent relaxation and endothelial independent nitric oxide dependent relaxation. RESULTS: AgNP instillation resulted in modest increase in selected serum cytokines with elevations in IL-2, IL-18, and IL-6. Instillation resulted in a derangement of vascular responses to constrictors serotonin or phenylephrine, as well as endothelial dependent relaxations with acetylcholine or endothelial independent relaxations by sodium nitroprusside in a capping and size dependent manner. Exposure to both 20 and 110 nm AgNP resulted in exacerbation cardiac I/R injury 1 day following IT instillation independent of capping agent with 20 nm AgNP inducing marginally greater injury. Seven days following IT instillation the expansion of I/R injury persisted but the greatest injury was associated with exposure to 110 nm PVP capped AgNP resulted in nearly a two-fold larger infarct size compared to naive. CONCLUSIONS: Exposure to AgNP may result in vascular dysfunction, a potentially maladaptive sensitization of the immune system to respond to a secondary insult (e.g., cardiac I/R) which may drive expansion of I/R injury at 1 and 7 days following IT instillation where the extent of injury could be correlated with capping agents and AgNP size. PMID- 27558115 TI - CT Fluoroscopy-Guided Transsacral Intervertebral Drainage for Pyogenic Spondylodiscitis at the Lumbosacral Junction. AB - PURPOSE: To retrospectively describe the feasibility and efficacy of CT fluoroscopy-guided transsacral intervertebral drainage for pyogenic spondylodiscitis at the lumbosacral junction with a combination of two interventional radiological techniques-CT-guided bone biopsy and abscess drainage. MATERIALS AND METHODS: Three patients with pyogenic spondylodiscitis at the lumbosacral junction were enrolled in this study between July 2013 and December 2015. The procedure of CT fluoroscopy-guided transsacral intervertebral drainage for pyogenic spondylodiscitis at the lumbosacral junction was as follows: the sacrum at S1 pedicle was penetrated with an 11-gauge (G) bone biopsy needle to create a path for an 8-French (F) pigtail drainage catheter. The bone biopsy needle was withdrawn, and an 18-G needle was inserted into the intervertebral space of the lumbosacral junction. Then, a 0.038-inch guidewire was inserted into the intervertebral space. Finally, the 8-F pigtail drainage catheter was inserted over the guidewire until its tip reached the intervertebral space. All patients received six-week antibiotics treatment. RESULTS: Successful placement of the drainage catheter was achieved for each patient without procedural complications. The duration of drainage was 17-33 days. For two patients, specific organisms were isolated; thus, definitive medical therapy was possible. All patients responded well to the treatment. CONCLUSIONS: CT fluoroscopy-guided transsacral intervertebral drainage for pyogenic spondylodiscitis at the lumbosacral junction is feasible and can be effective with a combination of two interventional techniques-CT fluoroscopy-guided bone biopsy and abscess drainage. PMID- 27558116 TI - Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis. AB - Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia. Primary hyperhidrosis is also thought to be the result of sympathetic dysregulation. We present the case of a patient treated with CT-guided, percutaneous T2 EtOH sympatholysis for craniofacial hyperhidrosis. The patient also suffered from postural orthostatic tachycardia syndrome for many years and was unresponsive to treatment. Immediately after sympatholysis, the patient experienced resolution of both craniofacial hyperhidrosis and postural orthostatic tachycardia syndrome. PMID- 27558117 TI - Effects of the APOE epsilon4 allele and education on cognitive function in Japanese centenarians. AB - Apolipoprotein E (APOE) epsilon4 allele and education have been reported to affect the cognitive function in young-old adults. However, the effects and interactions of the epsilon4 allele and education on cognitive function in very old age, particularly in centenarians, are not well known. We studied 542 Japanese centenarians. Using the data in total of 452 participants (74 men and 378 women, mean age 103.6 +/- 3.2 years) who were genotyped and assessed cognitive function with the Mini-Mental States Examination (MMSE), we examined the effects and interactions of the epsilon4 allele and education on the MMSE score. First, we coded education as three levels: low, middle, and high based on the formal educational levels (analysis 1). Second, to clarify the modifying effect of education, we adopted a new coding for education into two levels, considering a periodical background (around 1900) of gender differences in educational attainments (analysis 2). In analysis 1, the main effects of the epsilon4 allele and education on the MMSE score were significant after adjusting for age. Further, there was a significant three-way interaction effect between the epsilon4 allele, education, and gender on the MMSE. Analysis 2 showed that the modifying effect of the epsilon4 allele by education was observed only in women with the epsilon4 allele. These findings suggest that both the APOE epsilon4 allele and education appear to be associated with cognitive function even in centenarians, but the interaction between the epsilon4 allele and education might depend on gender in this cohort. PMID- 27558118 TI - Aerobic exercise increases resistance to oxidative stress in sedentary older middle-aged adults. A pilot study. AB - Older individuals who exercise regularly exhibit greater resistance to oxidative stress than their sedentary peers, suggesting that exercise can modify age associated loss of resistance to oxidative stress. However, we recently demonstrated that a single bout of exercise confers protection against a subsequent oxidative challenge in young, but not older adults. We therefore hypothesized that repeated bouts of exercise would be needed to increase resistance to an oxidative challenge in sedentary older middle-aged adults. Sedentary older middle-aged men and women (50-63 years, n = 11) participated in an 8-week exercise intervention. Maximal oxygen consumption was measured before and after the intervention. The exercise intervention consisted of three sessions per week, for 45 min at an intensity corresponding to 70-85 % maximal heart rate (HRmax). Resistance to oxidative stress was measured by F2-isoprostane response to a forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial before and after the exercise intervention. The intervention elicited a significant increase in maximal oxygen consumption (VO2max) (P < 0.0001). Baseline levels of F2-isoprostanes pre- and post-intervention did not differ, but the F2-isoprostane response to the I/R trial was significantly lower following the exercise intervention (time-by-trial interaction, P = 0.043). Individual improvements in aerobic fitness were associated with greater improvements in the F2-isoprostane response (r = -0.761, P = 0.011), further supporting the role of aerobic fitness in resistance to oxidative stress. These data demonstrate that regular exercise with improved fitness leads to increased resistance to oxidative stress in older middle-aged adults and that this measure is modifiable in previously sedentary individuals. PMID- 27558119 TI - Nine-year follow-up of progressive peri-stent contrast staining after Cypher sirolimus-eluting stent implantation: a case report. AB - A 62-year-old male underwent three percutaneous coronary interventions involving four bare metal stents and six Cypher sirolimus-eluting stents within 1 month. At the latest coronary angiographic examination, all of the Cypher stents, but none of the bare metal stents, exhibited peri-stent contrast staining. Moreover, these findings had progressively worsened over time, especially for lesions where two stents came into contact or stent fracture had occurred. It is rare for Cypher stent implantation to result in progressive peri-stent contrast staining, but patients who are treated with these stents should be carefully followed-up, including for stent thrombosis. PMID- 27558120 TI - A real-time RT-PCR for rapid detection and quantification of mosquito-borne alphaviruses. AB - Mosquito-borne alphaviruses are widely distributed throughout the world, causing important human illnesses. Therefore, the development of methods to enable early diagnosis of infections by alphavirus is essential. We show here the development and evaluation of a quantitative real-time RT-PCR using genus-specific primers to the nsP1 viral gene of all mosquito-borne alphaviruses. The specificity and sensitivity of the assay were tested using seven alphaviruses and RNA transcribed from Venezuelan equine encephalitis virus. The detection limits of real-time RT PCR ranged from 10 to 76 copies per ml. The melting temperature (TM) values for amplification of the alphavirus genomes were 83.05 degrees C and 85.28 degrees C. Interestingly, the assay suggested the possibility the arthritogenic alphaviruses with TM peaks of 84.83 to 85.28 degrees C and encephalitic alphaviruses of 83.34 degrees C to 84.68 degrees C could be discriminated both diseases. Real-time RT-PCR may prove very useful for the screening and preliminary diagnosis in outbreaks and surveillance studies as well as for measuring the viral load in pathogenesis studies. PMID- 27558121 TI - Erratum to: The phylogenetic and recombinational analysis of beak and feather disease virus Taiwan isolates. PMID- 27558122 TI - Increased pathogenicity of rabies virus due to modification of a non-coding region. AB - Sub-passaging of QS-05, a street rabies virus (RABV) isolate, in non-neuronal cells resulted in a virus with higher pathogenicity, QS-BHK-P7. Four full-length cDNA plasmids were constructed and the corresponding recombinant viruses were recovered: rQS-05, rQS-BHK-P7 and rQS05-2475G/rQS-BHK-P7-2475A (made by switching of intergenic P-M between these two backbones). rQS-BHK-P7-2475 A virus had eight instead of seven adenosines in its poly(A) sequence. Interestingly, mutant viruses with 6 or 8 adenosines infected more neuroblastoma cells than their parental ones. Mice that were infected intracerebrally and intramuscularly with rQS05-2475G and rQS-BHK-P7 exhibited highest mortality. However, mice infected with rQS-BHK-P7-2475AA had the shortest survival time. This study demonstrates that modifications in the non-coding region may play a role in determining the virulence of RABV. PMID- 27558124 TI - Complete nucleotide sequence of Magnaporthe oryzae partitivirus 1. AB - A novel double-stranded RNA (dsRNA) mycovirus, designated Magnaporthe oryzae partitivirus 1 (MoPV1), was isolated from a strain of the plant pathogenic fungus Magnaporthe oryzae. The MoPV1 genome has two dsRNA genome segments. The larger segment (1763 bp) has a single open reading frame (ORF) with a conserved RNA dependent RNA polymerase (RdRp) domain. The smaller segment (1491 bp) contains a single ORF encoding a putative coat protein (CP). Homology searches and phylogenetic analysis indicated that MoPV1 is a new member of the genus Gammapartitivirus. This is the first report of a mycovirus of the family Partitiviridae identified in Magnaporthe oryzae. PMID- 27558123 TI - The establishment and characteristics of cell-adapted IBV strain H120. AB - Avian infectious bronchitis virus is an important pathogen in poultry worldwide. Vaccination is the only effective way to prevent and control IBV infection. H120, one of the safest vaccine strains, which has been used worldwide as a primary vaccine, cannot adapt to passaged cells, which severely restricts the quality of the vaccine. Based on the reverse genetics of our previous research work, we constructed the recombinant R-H120-Beaudette-p65(S) strain by replacing the complete spike gene of H120 with the corresponding spike gene from the Beaudette p65 strain. Some biological characteristics, including replication kinetics, virulence and immunological properties of R-H120-Beaudette-p65(S) have been evaluated. The results showed that biological characteristics of R-H120-Beaudette p65(S), such as replication kinetics in embryonated chicken eggs (ECEs) and embryo virulence, were similar to those of H120. In addition, R-H120-Beaudette p65(S) could induce a similar antibody titre and provide up to 80 % immune protection in chickens challenged with the M41 strain. These results indicate that R-H120-Beaudette-p65(S) has the potential for further development as a cell adapted vaccine. PMID- 27558125 TI - IFN-stimulated gene expression is independent of the IFNL4 genotype in chronic HIV-1 infection. AB - This study aimed to evaluate the association between the IFNL4 rs368234815 (DeltaG/TT) dinucleotide polymorphism and the IFN response during chronic HIV-1 infection. We carried out genotyping analysis and measured the expression of IFN stimulated genes (ISGs) (myxovirus resistance protein A [MxA], ISG15, ISG56, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like [APOBEC] 3F and APOBEC3G) on peripheral blood mononuclear cells collected from naive and HAART treated HIV-1-infected patients. There were no statistically significant differences in endogenous ISGs mRNA levels among HIV-1-positive patients bearing different IFNL4 genotypes, suggesting that ISG expression is independent of the IFNL4 genotype in HIV-1 infection. PMID- 27558126 TI - Influence of weaning methods on the diaphragm after mechanical ventilation in a rat model. AB - BACKGROUND: Mechanical ventilation (MV) is associated with diaphragm weakness, a phenomenon termed ventilator-induced diaphragmatic dysfunction. Weaning should balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of a weak diaphragm, respectively. This study investigated which weaning method allows more efficient restoration of diaphragm homeostasis. METHODS: Rats (n = 8 per group) received 12 h of MV followed by either 12 h of pressure support ventilation (PSV) or intermittent spontaneous breathing trials (SBT) and were compared to rats euthanized after 12 h MV (CMV) and to acutely euthanized rats (CON). Force generation, activity of calpain-1 and caspase-3, oxidative stress, and markers of protein synthesis (phosphorylated AKT to total AKT) were measured in the diaphragm. RESULTS: Reduction of diaphragmatic force caused by CMV compared to CON was worsened with PSV and SBT (both p < 0.05 vs. CON and CMV). Both PSV and SBT reversed oxidative stress and calpain-1 activation caused by CMV. Reduced pAKT/AKT was observed after CMV and both weaning procedures. CONCLUSIONS: MV resulted in a loss of diaphragmatic contractility, which was aggravated in SBT and PSV despite reversal of oxidative stress and proteolysis. PMID- 27558127 TI - Fully automated, level set-based segmentation for knee MRIs using an adaptive force function and template: data from the osteoarthritis initiative. AB - BACKGROUND: This study focuses on osteoarthritis (OA), which affects millions of adults and occurs in knee cartilage. Diagnosis of OA requires accurate segmentation of cartilage structures. Existing approaches to cartilage segmentation of knee imaging suffer from either lack of fully automatic algorithm, sub-par segmentation accuracy, or failure to consider all three cartilage tissues. METHODS: We propose a novel segmentation algorithm for knee cartilages with level set-based segmentation method and novel template data. We used 20 normal subjects from osteoarthritis initiative database to construct new template data. We adopt spatial fuzzy C-mean clustering for automatic initialization of contours. Force function of our algorithm is modified to improve segmentation performance. RESULTS: The proposed algorithm resulted in dice similarity coefficients (DSCs) of 87.1, 84.8 and 81.7 % for the femoral, patellar, and tibial cartilage, respectively from 10 subjects. The DSC results showed improvements of 8.8, 4.3 and 3.5 % for the femoral, patellar, and tibial cartilage respectively compared to existing approaches. Our algorithm could be applied to all three cartilage structures unlike existing approaches that considered only two cartilage tissues. CONCLUSIONS: Our study proposes a novel fully automated segmentation algorithm adapted for three types of knee cartilage tissues. We leverage state-of-the-art level set approach with newly constructed knee template. The experimental results show that the proposed method improves the performance by an average of 5 % over existing methods. PMID- 27558128 TI - B chromosomes: from cytogenetics to systems biology. AB - Though hundreds to thousands of reports have described the distribution of B chromosomes among diverse eukaryote groups, a comprehensive theory of their biological role has not yet clearly emerged. B chromosomes are classically understood as a sea of repetitive DNA sequences that are poor in genes and are maintained by a parasitic-drive mechanism during cell division. Recent developments in high-throughput DNA/RNA analyses have increased the resolution of B chromosome biology beyond those of classical and molecular cytogenetic methods; B chromosomes contain many transcriptionally active sequences, including genes, and can modulate the activity of autosomal genes. Furthermore, the most recent knowledge obtained from omics analyses, which is associated with a systemic view, has demonstrated that B chromosomes can influence cell biology in a complex way, possibly favoring their own maintenance and perpetuation. PMID- 27558131 TI - Persistent atrial standstill following the Cox-maze III procedure: reversal with sustained atrial pacing. AB - Atrial standstill is a rare disorder of cardiac rhythm that is characterized by total absence of electrical activity in one or both atria. We report herein the case of a patient with atrial fibrillation and symptomatic 4.0 s pauses who received a ventricular demand pacemaker. The patient later underwent mitral valve replacement with a pericardial tissue valve and the Cox-maze III procedure for symptomatic mitral stenosis and atrial fibrillation. Following surgery, he developed atrial standstill and became pacemaker dependent. The pacemaker was later revised to an atrioventricular sequential pacemaker. Twelve hours after revision, atrioventricular sequential pacing was noted and mechanical function of the atria was confirmed by Doppler echocardiography. PMID- 27558130 TI - Novel advances in the treatment of osteoporosis. AB - INTRODUCTION: Osteoporosis is a significant public health issue affecting over half of women aged over 50. With an aging population, its importance is set to increase further over time. Prevention of fragility fractures avoids significant mortality and morbidity as well as saving significant direct and indirect costs to the economy. In this review, we discuss existing treatments to contextualize the treatment landscape, and demonstrate how our understanding of bone pathophysiology has led to novel therapies-in the form of combinations and altered durations of existing treatments, as well as newer drug therapies. SOURCES OF DATA: PubMed and Embase were searched for randomized controlled trials of new therapies for osteoporosis. These searches were supplemented with material presented in abstract form at international meetings. AREAS OF AGREEMENT: New drugs that appear promising in the treatment of osteoporosis include the cathepsin K inhibitor, monoclonal antibodies against sclerostin and parathyroid hormone-related protein analog. AREAS OF CONTROVERSY: Separate to the development of novel drug therapies is the issue of how best to use agents that are currently available to us; specifically which agent to choose, alone or in combination; duration of therapy; how best to identify patients at highest risk of fracture, and to ensure the highest possible adherence to medication. Many of these issues have been addressed in other excellent review papers, and will not be considered in detail here. GROWING POINTS: As with all new treatments, we await results of long-term use and experience in 'real life' patient populations. AREAS TIMELY FOR DEVELOPING RESEARCH: As alluded to above, data are urgently required regarding the optimal duration of therapy; use of combination therapy; ordering of therapies for best therapeutic effect. As stratified medicine becomes more strongly considered in all areas of therapy, its merits in osteoporosis as in other musculoskeletal conditions, is timely and valuable. PMID- 27558132 TI - Streptacidiphilus toruniensis sp. nov., isolated from a pine forest soil. AB - Two acidophilic actinobacteria, isolates NA14 and NF37T, were the subject of a polyphasic taxonomic study. Chemotaxonomic and morphological properties of the isolates were characteristic of the genus Streptacidiphilus. The isolates were shown to have identical 16S rRNA gene sequences and to be closely related to Streptacidiphilus neutrinimicus DSM 41755T (>99.9 %). However, DNA:DNA relatedness between isolate NF37T and the type strain of S. neutrinimicus was found to be low at 11.1 (+/-3.5) %. A broad range of phenotypic features were shown to distinguish the isolates from their close phylogenetic neighbours. These data shown that the isolates form a novel species of Streptacidiphilus for which the name Streptacidiphilus toruniensis sp. nov. is proposed. The type strain is NF37T (= DSM 102291T = NCIMB 15025T). PMID- 27558133 TI - Effects of Brevibacillus brevis FJAT-1501-BPA on growth performance, faecal microflora, faecal enzyme activities and blood parameters of weaned piglets. AB - A feeding expriment was performed to investigate the effects of dietary supplementation with Brevibacillus brevis FJAT-1501-BPA fermentation on the growth performance, faecal microflora, faecal enzyme activities and blood parameters of weaned piglets. A total of 150 weaned piglets were randomly assigned to different treatments groups, which were fed the same basic diet supplemented with 10, 1, 0.1, 0.01 and 0 % B. brevis FJAT-1501-BPA fermentation. The results showed that a diet supplemented with 10 % B. brevis FJAT-1501-BPA fermentation could significantly increase the final body weight (P < 0.05) and decrease feed to gain ratio, which was 37.1 % lower than that of the control group. The addition of B. brevis FJAT-1501-BPA exhibited a trend of reducing the contents of the Escherichia coli, Lactobacillus and Salmonella compared with the control. During the 35 day experimental period, cellulase and protease activities were significantly increased by the dietary inclusion of the B. brevis FJAT-1501 BPA fermentation (P < 0.05). The cellulase activity for piglets fed diet containing 1 % B. brevis FJAT-1501-BPA fermentation, 21.8 U/g, was highest among the different treatments. The protease activity for piglets fed diet containing 10 % B. brevis FJAT-1501-BPA fermentation, 50.4 U/g, was highest among the different treatments. The amylase and hemicellulase activities for piglets fed diet containing 10 % B. brevis FJAT-1501-BPA fermentation were significantly higher than those on the control diet and other treatments (P < 0.05). Moreover, usage of feed dietary supplementation with B. brevis FJAT-1501-BPA had positive effects on levels of enzymes and minerals in blood. The alkaline phosphatase, alanine aminotransferase, Fe and Mg concentrations for weaned piglets fed diet containing B. brevis FJAT-1501-BPA fermentation were significantly higher than for those on the control diet (P < 0.05). Furthermore, concentration of IgG in serum was higher in weaned piglets fed diet containing 1 % B. brevis FJAT-1501 BPA fermentation compared to other treatments. These results indicated that feeding with B. brevis FJAT-1501-BPA has the potential to improve growth performance, faecal microflora, faecal enzyme activities and blood parameters of weaned piglets. PMID- 27558134 TI - Taxonomy and physiological characterisation of Scheffersomyces titanus sp. nov., a new D-xylose-fermenting yeast species from China. AB - Three strains of a d-xylose-fermenting yeast species were isolated from the host beetle Dorcus titanus collected from two different localities in Henan Province, Central China. These strains formed two hat-shaped ascospores in conjugated and deliquescent asci. Multilocus phylogenetic analysis that included the nearly complete small subunit (SSU), the internal transcribed spacer (ITS) region and the D1/D2 domains of the large subunit (LSU) rDNAs, as well as RNA polymerase II largest subunit (RPB1) gene demonstrated that these strains represent a novel yeast species belonging to the genus Scheffersomyces. The phylogenetic analysis based on the nucleotide sequences of the xylose reductase (XYL1) gene supported the view that the new strains could be grouped as a unique species. Although this new species is highly similar to Scheffersomyces stipitis-like yeasts in terms of nrDNA sequences and morphological and physiological characteristics, the species can be clearly differentiated from its close relatives on the basis of the sequences of XYL1 and RPB1. Therefore, a novel yeast species, Scheffersomyces titanus sp. nov., is proposed to accommodate these strains. The type strain is NYNU 14712(T) (CICC 33061(T) = CBS 13926(T)). PMID- 27558135 TI - A Synthetic Dosage Lethal Genetic Interaction Between CKS1B and PLK1 Is Conserved in Yeast and Human Cancer Cells. AB - The CKS1B gene located on chromosome 1q21 is frequently amplified in breast, lung, and liver cancers. CKS1B codes for a conserved regulatory subunit of cyclin CDK complexes that function at multiple stages of cell cycle progression. We used a high throughput screening protocol to mimic cancer-related overexpression in a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential only when CKS1 is overexpressed, a synthetic dosage lethal (SDL) interaction. Mutations in multiple genes affecting mitotic entry and mitotic exit are highly enriched in the set of SDL interactions. The interactions between Cks1 and the mitotic entry checkpoint genes require the inhibitory activity of Swe1 on the yeast cyclin-dependent kinase (CDK), Cdc28. In addition, the SDL interactions of overexpressed CKS1 with mutations in the mitotic exit network are suppressed by modulating expression of the CDK inhibitor Sic1. Mutation of the polo-like kinase Cdc5, which functions in both the mitotic entry and mitotic exit pathways, is lethal in combination with overexpressed CKS1 Therefore we investigated the effect of targeting the human Cdc5 ortholog, PLK1, in breast cancers with various expression levels of human CKS1B Growth inhibition by PLK1 knockdown correlates with increased CKS1B expression in published tumor cell data sets, and this correlation was confirmed using shRNAs against PLK1 in tumor cell lines. In addition, we overexpressed CKS1B in multiple cell lines and found increased sensitivity to PLK1 knockdown and PLK1 drug inhibition. Finally, combined inhibition of WEE1 and PLK1 results in less apoptosis than predicted based on an additive model of the individual inhibitors, showing an epistatic interaction and confirming a prediction of the yeast data. Thus, identification of a yeast SDL interaction uncovers conserved genetic interactions that can affect human cancer cell viability. PMID- 27558136 TI - Growth Coordination During Drosophila melanogaster Imaginal Disc Regeneration Is Mediated by Signaling Through the Relaxin Receptor Lgr3 in the Prothoracic Gland. AB - Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that (1) extends larval development and (2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/insulin-like growth factor/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of nitric oxide synthase (NOS) in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homolog Lgr3, a leucine-rich repeat-containing G-protein-coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNA interference disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of NOS, and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing. PMID- 27558137 TI - Production of Small Noncoding RNAs from the flamenco Locus Is Regulated by the gypsy Retrotransposon of Drosophila melanogaster. AB - Protective mechanisms based on RNA silencing directed against the propagation of transposable elements are highly conserved in eukaryotes. The control of transposable elements is mediated by small noncoding RNAs, which derive from transposon-rich heterochromatic regions that function as small RNA-generating loci. These clusters are transcribed and the precursor transcripts are processed to generate Piwi-interacting RNAs (piRNAs) and endogenous small interfering RNAs (endo-siRNAs), which silence transposable elements in gonads and somatic tissues. The flamenco locus is a Drosophila melanogaster small RNA cluster that controls gypsy and other transposable elements, and has played an important role in understanding how small noncoding RNAs repress transposable elements. In this study, we describe a cosuppression mechanism triggered by new euchromatic gypsy insertions in genetic backgrounds carrying flamenco alleles defective in gypsy suppression. We found that the silencing of gypsy is accompanied by the silencing of other transposons regulated by flamenco, and of specific flamenco sequences from which small RNAs against gypsy originate. This cosuppression mechanism seems to depend on a post-transcriptional regulation that involves both endo-siRNA and piRNA pathways and is associated with the occurrence of developmental defects. In conclusion, we propose that new gypsy euchromatic insertions trigger a post transcriptional silencing of gypsy sense and antisense sequences, which modifies the flamenco activity. This cosuppression mechanism interferes with some developmental processes, presumably by influencing the expression of specific genes. PMID- 27558139 TI - Insights into Interspecific Hybridization Events in Allotetraploid Cotton Formation from Characterization of a Gene-Regulating Leaf Shape. AB - The morphology of cotton leaves varies considerably. Phenotypes, including okra, sea-island, super-okra, and broad leaf, are controlled by a multiple allele locus, L2 Okra leaf (L2 degrees ) is an incomplete mutation that alters leaf shape by increasing the length of lobes with deeper sinuses. Using a map-based cloning strategy, we cloned the L2 locus gene, which encodes a LATE MERISTEM IDENTITY 1 (LMI1)-like transcription factor (GhOKRA). Silencing GhOKRA leads to a change in phenotype from okra to broad leaf. Overexpression of GhOKRA in Arabidopsis thaliana greatly increases the degree of the leaf lobes and changes the leaf shape. Premature termination of translation in GhOKRA results in the production of broad leaves. The sequences of OKRA from diploid progenitor D genome species, and wild races and domesticated allotetraploid cottons in Gossypium hirsutum show that a premature termination mutation occurred before and after the formation of tetraploid cotton, respectively. This study provides genomic insights into the two interspecific hybridization events: one produced the present broad leaf and another formed okra leaf phenotype with complete OKRA, that occurred during allotetraploid cotton formation. PMID- 27558138 TI - Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila. AB - The assembly and function of mitochondria require coordinated expression from two distinct genomes, the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mutations in either genome can be a source of phenotypic variation, yet their coexpression has been largely overlooked as a source of variation, particularly in the emerging paradigm of mitochondrial replacement therapy. Here we tested how the transcriptome responds to mtDNA and nDNA variation, along with mitonuclear interactions (mtDNA * nDNA) in Drosophila melanogaster We used two mtDNA haplotypes that differ in a substantial number of single nucleotide polymorphisms, with >100 amino acid differences. We placed each haplotype on each of two D. melanogaster nuclear backgrounds and tested for transcription differences in both sexes. We found that large numbers of transcripts were differentially expressed between nuclear backgrounds, and that mtDNA type altered the expression of nDNA genes, suggesting a retrograde, trans effect of mitochondrial genotype. Females were generally more sensitive to genetic perturbation than males, and males demonstrated an asymmetrical effect of mtDNA in each nuclear background; mtDNA effects were nuclear-background specific. mtDNA sensitive genes were not enriched in male- or female-limited expression space in either sex. Using a variety of differential expression analyses, we show the responses to mitonuclear covariation to be substantially different between the sexes, yet the mtDNA genes were consistently differentially expressed across nuclear backgrounds and sexes. Our results provide evidence that the main mtDNA effects can be consistent across nuclear backgrounds, but the interactions between mtDNA and nDNA can lead to sex-specific global transcript responses. PMID- 27558140 TI - Cross-Sectional Associations of Objectively-Measured Physical Activity and Sedentary Time with Body Composition and Cardiorespiratory Fitness in Mid Childhood: The PANIC Study. AB - BACKGROUND: The minimum intensity of physical activity (PA) that is associated with favourable body composition and cardiorespiratory fitness (CRF) remains unknown. OBJECTIVE: To investigate cross-sectional associations of PA and sedentary time (ST) with body composition and CRF in mid-childhood. METHODS: PA, ST, body composition and CRF were measured in a population-based sample of 410 children (aged 7.6 +/- 0.4 years). Combined heart-rate and movement sensing provided estimates of PA energy expenditure (PAEE, kJ/kg/day) and time (min/day) at multiple fine-grained metabolic equivalent (MET) levels, which were also collapsed to ST and light PA (LPA), moderate PA (MPA) and vigorous PA (VPA). Fat mass index (FMI, kg/m2), trunk fat mass index (TFMI, kg/m2) and fat-free mass index (FFMI, kg/m2.5) were derived from dual-energy X-ray absorptiometry. Maximal workload from a cycle ergometer test provided a measure of CRF (W/kg FFM). Linear regression and isotemporal substitution models were used to investigate associations. RESULTS: The cumulative time above 2 METs (221 J/min/kg) was inversely associated with FMI and TFMI in both sexes (p < 0.001) whereas time spent above 3 METs was positively associated with CRF (p <= 0.002); CRF increased and adiposity decreased dose-dependently with increasing MET levels. ST was positively associated with FMI and TFMI (p < 0.001) but there were inverse associations between all PA categories (including LPA) and adiposity (p <= 0.002); the magnitude of these associations depended on the activity being displaced in isotemporal substitution models but were consistently stronger for VPA. PAEE, MPA and to a greater extent VPA, were all positively related to CRF (p <= 0.001). CONCLUSIONS: PA exceeding 2 METs is associated with lower adiposity in mid-childhood, whereas PA of 3 METs is required to benefit CRF. VPA was most beneficial for fitness and fatness, from a time-for-time perspective, but displacing any lower-for-higher intensity may be an important first-order public health strategy. Clinical trial registry number (website): NCT01803776 ( https://clinicaltrials.gov/ct2/show/NCT01803776 ). PMID- 27558141 TI - A Comparison of Cognitive Function in Former Rugby Union Players Compared with Former Non-Contact-Sport Players and the Impact of Concussion History. AB - AIM: This study investigated differences in cognitive function between former rugby and non-contact-sport players, and assessed the association between concussion history and cognitive function. METHODS: Overall, 366 former players (mean +/- standard deviation [SD] age 43.3 +/- 8.2 years) were recruited from October 2012 to April 2014. Engagement in sport, general health, sports injuries and concussion history, and demographic information were obtained from an online self-report questionnaire. Cognitive functioning was assessed using the online CNS Vital Signs neuropsychological test battery. Cohen's d effect size statistics were calculated for comparisons across player groups, concussion groups (one or more self-reported concussions versus no concussions) and between those groups with CNS Vital Signs age-matched norms (US norms). Individual differences within groups were represented as SDs. RESULTS: The elite-rugby group (n = 103) performed worse on tests of complex attention, processing speed, executive functioning, and cognitive flexibility than the non-contact-sport group (n = 65), and worse than the community-rugby group (n = 193) on complex attention. The community-rugby group performed worse than the non-contact group on executive functioning and cognitive flexibility. Compared with US norms, all three former player groups performed worse on verbal memory and reaction time; rugby groups performed worse on processing speed, cognitive flexibility and executive functioning; and the community-rugby group performed worse on composite memory. The community-rugby group and non-contact-sport group performed slightly better than US norms on complex attention, as did the elite-rugby group for motor speed. All three player groups had greater individual differences than US norms on composite memory, verbal memory and reaction time. The elite-rugby group had greater individual differences on processing speed and complex attention, and the community-rugby group had greater individual differences on psychomotor speed and motor speed. The average number of concussions recalled per player was greater for elite rugby and community rugby than non-contact sport. Former players who recalled one or more concussions (elite rugby, 85 %; community rugby, 77 %; non contact sport, 23 %) had worse scores on cognitive flexibility, executive functioning, and complex attention than players who did not recall experiencing a concussion. CONCLUSIONS: Past participation in rugby or a history of concussion were associated with small to moderate neurocognitive deficits (as indicated by worse CNS Vital Signs scores) in athletes post retirement from competitive sport. PMID- 27558142 TI - Finite-Size and Composition-Driven Topological Phase Transition in (Bi1-xInx)2Se3 Thin Films. AB - In a topological insulator (TI), if its spin-orbit coupling (SOC) strength is gradually reduced, the TI eventually transforms into a trivial insulator beyond a critical point of SOC, at which point the bulk gap closes: this is the standard description of the topological phase transition (TPT). However, this description of TPT, driven solely by the SOC (or something equivalent) and followed by closing and reopening of the bulk band gap, is valid only for infinite-size samples, and little is known how TPT occurs for finite-size samples. Here, using both systematic transport measurements on interface-engineered (Bi1-xInx)2Se3 thin films and theoretical simulations (with animations in the Supporting Information), we show that description of TPT in finite-size samples needs to be substantially modified from the conventional picture of TPT due to surface-state hybridization and bulk confinement effects. We also show that the finite-size TPT is composed of two separate transitions, topological-normal transition (TNT) and metal-insulator transition (MIT), by providing a detailed phase diagram in the two-dimensional phase space of sample size and SOC strength. PMID- 27558144 TI - [Not Available]. PMID- 27558143 TI - Hyperlipidemia induced by high-fat diet enhances dentin formation and delays dentin mineralization in mouse incisor. AB - Dyslipidemia has become a serious health problem in children and adolescents worldwide for its high prevalence. Since hard tissues of permanent teeth form mainly during this period and lipids are actively involved in tooth development, the effects of hyperlipidemia on dental tissue formation and mineralization need to be illustrated. In this study, hyperlipidemia model was established in mice fed with high-fat diet (HFD). Micro-CT and histomorphological analyses were performed on the mandibular bones to assess the morphological changes of the mandibular incisor and first molar. After 4 weeks of HFD feeding, mice had significantly elevated serum lipid levels compared with mice fed with control diet. After 8 weeks, the mandibular incisor presented significantly increased dentin thickness and decreased diameter of pulp cavity in HFD-fed mice compared with control diet-fed mice, while its gross morphology and enamel thickness were not altered. In the mandibular first molar, dentin thickness of root did not show difference between the two groups. Histological section showed that mandibular incisor of HFD-fed mice manifested a wider predentin region and a lower mineral apposition rate compared with that of the control mice. In conclusion, hyperlipidemia induced by HFD feeding enhances dentin formation and delays dentin mineralization in the developing mouse incisor. PMID- 27558145 TI - [Not Available]. PMID- 27558146 TI - [Not Available]. PMID- 27558147 TI - [Not Available]. PMID- 27558148 TI - [Not Available]. PMID- 27558149 TI - [Not Available]. PMID- 27558150 TI - Liposomal bupivacaine peripheral nerve block for the management of postoperative pain. AB - BACKGROUND: Postoperative pain remains a significant issue with poor perioperative pain management associated with an increased risk of morbidity and mortality. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained release. OBJECTIVES: To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration peripheral nerve block for the management of postoperative pain. SEARCH METHODS: We identified randomised trials of liposomal bupivacaine peripheral nerve block for the management of postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), Ovid MEDLINE (1946 to January Week 1 2016), Ovid MEDLINE In-Process (14 January 2016), EMBASE (1974 to 13 January 2016), ISI Web of Science (1945 to 14 January 2016), and reference lists of retrieved articles. We sought unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. The date of the most recent search was 15 January 2016. SELECTION CRITERIA: Randomised, double-blind, placebo- or active-controlled clinical trials of a single dose of liposomal bupivacaine administered as a peripheral nerve block in adults aged 18 years or over undergoing elective surgery at any surgical site. We included trials if they had at least two comparison groups for liposomal bupivacaine peripheral nerve block compared with placebo or other types of analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We performed analyses using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5. We planned to perform a meta-analysis, however there were insufficient data to ensure a clinically meaningful answer; as such we have produced a 'Summary of findings' table in a narrative format, and where possible we assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: We identified seven studies that met inclusion criteria for this review. Three were recorded as completed (or terminated) but no results were published. Of the remaining four studies (299 participants): two investigated liposomal bupivacaine transversus abdominis plane (TAP) block, one liposomal bupivacaine dorsal penile nerve block, and one ankle block. The study investigating liposomal bupivacaine ankle block was a Phase II dose-escalating/de-escalating trial presenting pooled data that we could not use in our analysis.The studies did not report our primary outcome, cumulative pain score between 0 and 72 hours, and secondary outcomes, mean pain score at 12, 24, 48, 72, or 96 hours. One study reported no difference in mean pain score during the first, second, and third postoperative 24-hour periods in participants receiving liposomal bupivacaine TAP block compared to no TAP block. Two studies, both in people undergoing laparoscopic surgery under TAP block, investigated cumulative postoperative opioid dose, reported opposing findings. One found a lower cumulative opioid consumption between 0 and 72 hours compared to bupivacaine hydrochloride TAP block and one found no difference during the first, second, and third postoperative 24-hour periods compared to no TAP block. No studies reported time to first postoperative opioid or percentage not requiring opioids over the initial 72 hours. No studies reported a health economic analysis or patient reported outcome measures (outside of pain). The review authors sought data regarding adverse events but none were available, however there were no withdrawals reported to be due to adverse events.Using GRADE, we considered the quality of evidence to be very low with any estimate of effect very uncertain and further research very likely to have an important impact on our confidence in the estimate of effect. All studies were at high risk of bias due to their small sample size (fewer than 50 participants per arm) leading to uncertainty around effect estimates. Additionally, inconsistency of results and sparseness of data resulted in further downgrading of the quality of the data. AUTHORS' CONCLUSIONS: A lack of evidence has prevented an assessment of the efficacy of liposomal bupivacaine administered as a peripheral nerve block. At present there is a lack of data to support or refute the use of liposomal bupivacaine administered as a peripheral nerve block for the management of postoperative pain. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. PMID- 27558151 TI - Ovarian cancer. AB - Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. PMID- 27558152 TI - Scientific Skill Assessment of Basic Surgical Dissection and Overall Laparoscopic Performance. AB - To improve surgical education, objective and scientific skill assessments are required. There are two types of skill evaluations: assessments of basic surgical skills and assessments of overall surgical performance. To establish a reliable assessment method for surgical dissection, we measured the force applied on the tip of a surgical instrument during dissection of the renal vessels of pigs. The experiments revealed that, during surgical dissection, expert laparoscopic surgeons applied vertical force at the beginning of the stroke and then horizontal force, with minimum vertical force, at the end of the stroke. As an assessment of overall surgical performance, the Endoscopic Surgical Qualification system was developed and has been used for 12 years in Japan. More than 3700 surgeons, including urologists, were determined to have appropriate laparoscopic surgical skills after assessments of unedited videos by referees. PMID- 27558153 TI - Tao-Hong-Si-Wu Decoction ameliorates steroid-induced avascular necrosis of the femoral head by regulating the HIF-1alpha pathway and cell apoptosis. AB - The aim of this study was to corroborate the hypothesis that Tao-Hong-Si-Wu Decoction (THSWD) affects steroid-induced avascular necrosis of the femoral head (SANFH) by regulating the hypoxia-inducible factor 1alpha (HIF-1alpha) pathway. Forty-eight New Zealand rabbits were randomly divided into a normal control group (NC group), a model group (SANFH group), a THSWD group, and a dimethyloxalylglycine group (DMOG group). Rabbits in the SANFH group were injected with both horse serum and methylprednisolone. Rabbits in the THSWD group were gavaged with THSWD in addition to receiving the same treatment as the SANFH group. Rabbits in the DMOG group were injected with extra DMOG in conjunction with the same treatment as the SANFH group. Rabbits in the NC group received the same amount of normal saline. Eight weeks after steroid treatment, the femoral heads of rabbits were removed to examine HIF-1alpha, vascular endothelial growth factor (VEGF), caspase-3, and bcl-2. Results indicated that THSWD significantly promoted the expression of HIF-1alpha and VEGF in the femoral head tissue of rabbits and markedly inhibit the apoptosis of osteocytes, chondrocytes, and bone marrow cells. In addition, THSWD suppressed caspase-3 expression and induced bcl 2 expression in femoral head tissues. In conclusion, THSWD can suppress SANFH by regulating the HIF-1alpha pathway and cell apoptosis. PMID- 27558154 TI - Identification of therapeutic targets applicable to clinical strategies in ovarian cancer. AB - BACKGROUND: shRNA-mediated lethality screening is a useful tool to identify essential targets in cancer biology. Ovarian cancer (OC) is extremely heterogeneous and most cases are advanced stages at diagnosis. OC has a high response rate initially, but becomes resistant to standard chemotherapy. We previously employed high throughput global shRNA sensitization screens to identify NF-kB related pathways. Here, we re-analyzed our previous shRNA screens in an unbiased manner to identify clinically applicable molecular targets. METHODS: We proceeded with siRNA lethality screening using the top 55 genes in an expanded set of 6 OC cell lines. We investigated clinical relevance of candidate targets in The Cancer Genome Atlas OC dataset. To move these findings towards the clinic, we chose four pharmacological inhibitors to recapitulate the top siRNA effects: Oxozeaenol (for MAP3K7/TAK1), BI6727 (PLK1), MK1775 (WEE1), and Lapatinib (ERBB2). Cytotoxic effects were measured by cellular viability assay, as single agents and in 2-way combinations. Co-treatments were evaluated in either sequential or simultaneous exposure to drug for short term and extended periods to simulate different treatment strategies. RESULTS: Loss-of-function shRNA screens followed by short-term siRNA validation screens identified therapeutic targets in OC cells. Candidate genes were dysregulated in a subset of TCGA OCs although the alterations of these genes showed no statistical significance to overall survival. Pharmacological inhibitors such as Oxozeaenol, BI6727, and MK1775 showed cytotoxic effects in OC cells regardless of cisplatin responsiveness, while all OC cells tested were cytostatic to Lapatinib. Co treatment with BI6727 and MK1775 at sub-lethal concentrations was equally potent to BI6727 alone at lethal concentrations without cellular re-growth after the drugs were washed off, suggesting the co-inhibition at reduced dosages may be more efficacious than maximal single-agent cytotoxic concentrations. CONCLUSIONS: Loss-of-function screen followed by in vitro target validation using chemical inhibitors identified clinically relevant targets. This approach has the potential to systematically refine therapeutic strategies in OC. These molecular target-driven strategies may provide additional therapeutic options for women whose tumors have become refractory to standard chemotherapy. PMID- 27558155 TI - A fast multispectral light synthesiser based on LEDs and a diffraction grating. AB - Optical experiments often require fast-switching light sources with adjustable bandwidths and intensities. We constructed a wavelength combiner based on a reflective planar diffraction grating and light emitting diodes with emission peaks from 350 to 630 nm that were positioned at the angles corresponding to the first diffraction order of the reversed beam. The combined output beam was launched into a fibre. The spacing between 22 equally wide spectral bands was about 15 nm. The time resolution of the pulse-width modulation drivers was 1 ms. The source was validated with a fast intracellular measurement of the spectral sensitivity of blowfly photoreceptors. In hyperspectral imaging of Xenopus skin circulation, the wavelength resolution was adequate to resolve haemoglobin absorption spectra. The device contains no moving parts, has low stray light and is intrinsically capable of multi-band output. Possible applications include visual physiology, biomedical optics, microscopy and spectroscopy. PMID- 27558156 TI - Ca2+-activated Cl- channel currents in mammary secretory cells from lactating mouse. AB - The Cl- secretion via Ca2+-activated Cl- channel (CaCC) is critical for fluid secretion in exocrine glands like the salivary gland. Also in the mammary gland, it has been hypothesized that CaCC plays an important role in the secretion of Cl and aqueous phase of milk. However, there has been no evidence for the functional expression of CaCC in native mammary secretory (MS) cells of lactating animals. We therefore assessed membrane current in MS cells that were freshly isolated from lactating mice using whole cell patch-clamp techniques. In MS cells, we detected CaCC current that exhibited the following characteristics: 1) Ca2+-dependent activation at the concentrations of submicromolar range; 2) voltage-dependent activation; 3) slow kinetics for activation and deactivation; 4) outward rectification of the steady-state current; 5) anion permeability in the sequence of I- > NO3- > Br- > Cl- >> glutamate; 6) inhibition by Cl- channel blockers (niflumic acid, DIDS, and CaCCinh-A01). These characteristics of native CaCC current were similar to reported characteristics of heterologously expressed TMEM16A. RT-PCR analyses showed the expression of multiple CaCC channels including TMEM16A, Best1, and Best3 in the mammary glands of lactating mice. Immunohistochemical staining revealed the localization of TMEM16A protein at the apical membrane of the MS cells. Collectively, our data strongly suggest that MS cells functionally express CaCC, which is at least partly constituted by TMEM16A. The CaCC such as TMEM16A at the apical membrane of the MS cells may influence the quantity and/or quality of milk. PMID- 27558157 TI - Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies. AB - SLC4A11, a member of the SLC4 family of bicarbonate transporters, is a widely expressed integral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11 cause some cases of the blinding corneal dystrophies, congenital hereditary endothelial dystrophy, and Fuchs endothelial corneal dystrophy. These diseases are marked by fluid accumulation in the corneal stroma, secondary to defective fluid reabsorption by the corneal endothelium. The role of SLC4A11 in these corneal dystrophies is not firmly established, as SLC4A11 function remains unclear. To clarify the normal function(s) of SLC4A11, we characterized the protein following expression in the simple, low-background expression system Xenopus laevis oocytes. Since plant and fungal SLC4A11 orthologs transport borate, we measured cell swelling associated with accumulation of solute borate. The plant water/borate transporter NIP5;1 manifested borate transport, whereas human SLC4A11 did not. SLC4A11 supported osmotically driven water accumulation that was electroneutral and Na+ independent. Studies in oocytes and HEK293 cells could not detect Na+-coupled HCO3- transport or Cl-/HCO3- exchange by SLC4A11. SLC4A11 mediated electroneutral NH3 transport in oocytes. Voltage-dependent OH- or H+ movement was not measurable in SLC4A11-expressing oocytes, but SLC4A11 expressing HEK293 cells manifested low-level cytosolic acidification at baseline. In mammalian cells, but not oocytes, OH-/H+ conductance may arise when SLC4A11 activates another protein or itself is activated by another protein. These data argue against a role of human SLC4A11 in bicarbonate or borate transport. This work provides additional support for water and ammonia transport by SLC4A11. When expressed in oocytes, SLC4A11 transported NH3, not NH3/H. PMID- 27558158 TI - Malignant hyperthermia-associated mutations in the S2-S3 cytoplasmic loop of type 1 ryanodine receptor calcium channel impair calcium-dependent inactivation. AB - Channel activities of skeletal muscle ryanodine receptor (RyR1) are activated by micromolar Ca2+ and inactivated by higher (~1 mM) Ca2+ To gain insight into a mechanism underlying Ca2+-dependent inactivation of RyR1 and its relationship with skeletal muscle diseases, we constructed nine recombinant RyR1 mutants carrying malignant hyperthermia or centronuclear myopathy-associated mutations and determined RyR1 channel activities by [3H]ryanodine binding assay. These mutations are localized in or near the RyR1 domains which are responsible for Ca2+-dependent inactivation of RyR1. Four RyR1 mutations (F4732D, G4733E, R4736W, and R4736Q) in the cytoplasmic loop between the S2 and S3 transmembrane segments (S2-S3 loop) greatly reduced Ca2+-dependent channel inactivation. Activities of these mutant channels were suppressed at 10-100 MUM Ca2+, and the suppressions were relieved by 1 mM Mg2+ The Ca2+- and Mg2+-dependent regulation of S2-S3 loop RyR1 mutants are similar to those of the cardiac isoform of RyR (RyR2) rather than wild-type RyR1. Two mutations (T4825I and H4832Y) in the S4-S5 cytoplasmic loop increased Ca2+ affinities for channel activation and decreased Ca2+ affinities for inactivation, but impairment of Ca2+-dependent inactivation was not as prominent as those of S2-S3 loop mutants. Three mutations (T4082M, S4113L, and N4120Y) in the EF-hand domain showed essentially the same Ca2+-dependent channel regulation as that of wild-type RyR1. The results suggest that nine RyR1 mutants associated with skeletal muscle diseases were differently regulated by Ca2+ and Mg2+ Four malignant hyperthermia-associated RyR1 mutations in the S2-S3 loop conferred RyR2-type Ca2+- and Mg2+-dependent channel regulation. PMID- 27558159 TI - Chenodeoxycholic acid requires activation of EGFR, EPAC, and Ca2+ to stimulate CFTR-dependent Cl- secretion in human colonic T84 cells. AB - Bile acids are known to initiate intricate signaling events in a variety of tissues, primarily in the liver and gastrointestinal tract. Of the known bile acids, only the 7alpha-dihydroxy species, deoxycholic acid and chenodeoxycholic acid (CDCA), and their conjugates, activate processes that stimulate epithelial Cl- secretion. We have previously published that CDCA acts in a rapid manner to stimulate colonic ion secretion via protein kinase A (PKA)-mediated activation of the dominant Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) (Ao M, Sarathy J, Domingue J, Alrefai WA, and Rao MC. Am J Physiol Cell Physiol 305: C447-C456, 2013); however, PKA signaling did not account for the entire CDCA response. Here we show that in human colonic T84 cells, CDCA's induction of CFTR activity, measured as changes in short-circuit current (Isc), is dependent on epidermal growth factor receptor (EGFR) activation and does not involve the bile acid receptors TGR5 or farnesoid X receptor. CDCA activation of Cl- secretion does not require Src, mitogen-activated protein kinases, or phosphoinositide 3-kinase downstream of EGFR but does require an increase in cytosolic Ca2+ In addition to PKA signaling, we found that the CDCA response requires the novel involvement of the exchange protein directly activated by cAMP (EPAC). EPAC is a known hub for cAMP and Ca2+ cross talk. Downstream of EPAC, CDCA activates Rap2, and changes in free cytosolic Ca2+ were dependent on both EPAC and EGFR activation. This study establishes the complexity of CDCA signaling in the colonic epithelium and shows the contribution of EGFR, EPAC, and Ca2+ in CDCA-induced activation of CFTR-dependent Cl- secretion. PMID- 27558160 TI - The myonuclear domain is not maintained in skeletal muscle during either atrophy or programmed cell death. AB - Skeletal muscle mass can increase during hypertrophy or decline dramatically in response to normal or pathological signals that trigger atrophy. Many reports have documented that the number of nuclei within these cells is also plastic. It has been proposed that a yet-to-be-defined regulatory mechanism functions to maintain a relatively stable relationship between the cytoplasmic volume and nuclear number within the cell, a phenomenon known as the "myonuclear domain" hypothesis. While it is accepted that hypertrophy is typically associated with the addition of new nuclei to the muscle fiber from stem cells such as satellite cells, the loss of myonuclei during atrophy has been controversial. The intersegmental muscles from the tobacco hawkmoth Manduca sexta are composed of giant syncytial cells that undergo sequential developmental programs of atrophy and programmed cell death at the end of metamorphosis. Since the intersegmental muscles lack satellite cells or regenerative capacity, the tissue is not "contaminated" by these nonmuscle nuclei. Consequently, we monitored muscle mass, cross-sectional area, nuclear number, and cellular DNA content during atrophy and the early phases of cell death. Despite a ~75-80% decline in muscle mass and cross-sectional area during the period under investigation, there were no reductions in nuclear number or DNA content, and the myonuclear domain was reduced by ~85%. These data suggest that the myonuclear domain is not an intrinsic property of skeletal muscle and that nuclei persist through atrophy and programmed cell death. PMID- 27558161 TI - The impact of long-lasting microbial larvicides in reducing malaria transmission and clinical malaria incidence: study protocol for a cluster randomized controlled trial. AB - BACKGROUND: The massive scale-up of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has led to a substantial increase in malaria vector insecticide resistance as well as in increased outdoor transmission, both of which hamper the effectiveness and efficiency of ITN and IRS. Long-lasting microbial larvicide can be a cost-effective new supplemental intervention tool for malaria control. METHODS/DESIGN: We will implement the long-lasting microbial larvicide intervention in 28 clusters in two counties in western Kenya. We will test FourStar controlled release larvicide (6 % by weight Bacillus thuringiensis israelensis and 1 % Bacillus sphaerius) by applying FourStar controlled release granule formulation, 90-day briquettes, and 180-day briquettes in different habitat types. The primary endpoint is clinical malaria incidence rate and the secondary endpoint is malaria vector abundance and transmission intensity. The intervention will be conducted as a two-step approach. First, we will conduct a four-cluster trial (two clusters per county, with one of the two clusters randomly assigned to the intervention arm) to optimize the larvicide application scheme. Second, we will conduct an open-label, cluster-randomized trial to evaluate the effectiveness and cost-effectiveness of the larvicide. Fourteen clusters in each county will be assigned to intervention (treatment) or no intervention (control) by a block randomization on the basis of clinical malaria incidence, vector density, and human population size per site. We will treat each treatment cluster with larvicide for three rounds at 4-month intervals, followed by no treatment for the following 8 months. Next, we will switch the control and treatment sites. The former control sites will receive three rounds of larvicide treatment at appropriate time intervals, and former treatment sites will receive no larvicide. We will monitor indoor and outdoor vector abundance using CO2 baited CDC light traps equipped with collection bottle rotators. Clinical malaria data will be aggregated from government-run malaria treatment centers. DISCUSSION: Since current first-line vector intervention methods do not target outdoor transmission and will select for higher insecticide resistance, new methods beyond bed nets and IRS should be considered. Long-lasting microbial larviciding represents a promising new tool that can target both indoor and outdoor transmission and alleviate the problem of pyrethroid resistance. It also has the potential to diminish costs by reducing larvicide reapplications. If successful, it could revolutionize malaria vector control in Africa, just as long lasting bed nets have done. TRIAL REGISTRATION: U.S. National Institute of Health, study ID NCT02392832 . Registered on 3 February 2015. PMID- 27558163 TI - Urethral inflammatory response to ureaplasma is significantly lower than to Mycoplasma genitalium and Chlamydia trachomatis. AB - A non-syndromic approach to treatment of people with non-gonococcal urethritis (NGU) requires identification of pathogens and understanding of the role of those pathogens in causing disease. The most commonly detected and isolated micro organisms in the male urethral tract are bacteria belonging to the family of Mycoplasmataceae, in particular Ureaplasma urealyticum and Ureaplasma parvum. To better understand the role of these Ureaplasma species in NGU, we have performed a prospective analysis of male patients voluntarily attending a drop in STI clinic in Oslo. Of 362 male patients who were tested for NGU using microscopy of urethral smears, we found the following sexually transmissible micro-organisms: 16% Chlamydia trachomatis, 5% Mycoplasma genitalium, 14% U. urealyticum, 14% U. parvum and 5% Mycoplasma hominis. We found a high concordance in detecting in turn U. urealyticum and U. parvum using 16s rRNA gene and ureD gene as targets for nucleic acid amplification testing (NAAT). Whilst there was a strong association between microscopic signs of NGU and C. trachomatis infection, association of M. genitalium and U. urealyticum infections in turn were found only in patients with severe NGU (>30 polymorphonuclear leucocytes, PMNL/high powered fields, HPF). U. parvum was found to colonise a high percentage of patients with no or mild signs of NGU (0-9 PMNL/HPF). We conclude that urethral inflammatory response to ureaplasmas is less severe than to C. trachomatis and M. genitalium in most patients and that testing and treatment of ureaplasma-positive patients should only be considered when other STIs have been ruled out. PMID- 27558162 TI - Household, psychosocial, and individual-level factors associated with fruit, vegetable, and fiber intake among low-income urban African American youth. AB - BACKGROUND: Childhood obesity, one of the greatest challenges to public health, disproportionately affects low-income urban minority populations. Fruits and vegetables (FV) are nutrient dense foods that may be inversely associated with excessive weight gain. We aimed to identify the individual characteristic, psychosocial, and household factors influencing FV and fiber consumption in low income African-American (AA) youth in Baltimore, MD. METHODS: Cross-sectional analysis of data collected from 285 low-income AA caregiver-youth (age range: 10 14 y) dyads participating in the baseline evaluation of the B'More Healthy Communities for Kids obesity prevention trial. The Kid's Block FFQ was used to estimate daily intakes of FV (including 100 % fruit juice) and dietary fiber. Questionnaires were used to assess household socio-demographics, caregiver and youth food purchasing and preparation behavior, and youth psychosocial information. Ordered logit regression analyses were conducted to examine psychosocial and food-related behavior associated with FV and dietary fiber intake (quartile of intake) controlling for youth age, sex, BMI percentile, total calorie intake and household income. RESULTS: On average, youth consumed 1.5 +/- 1.1 (M +/- SD) servings of fruit, 1.8 +/- 1.7 serving of vegetables, and 15.3 +/- 10.9 g of fiber/day. There were no differences by gender, age or household income. Greater youth's healthy eating intentions and self-efficacy scores were associated with greater odds ratio for higher intake of FV and fiber (Intention: ORfruit 1.22; 95 % CI: 1.06-1.41, ORvegetable 1.31; 1.15-1.51 and ORfiber 1.46; 1.23-1.74, Self-efficacy: ORfruit 1.07; 1.03-1.12, ORvegetable 1.04; 1.01-1.09, ORfiber 1.10; 1.04-1.16). Youth receiving free/low-cost breakfast were more than twice as likely to have higher fiber intake than those who did not receive free breakfast (OR 2.7; 1.10; 6.9). In addition, youth shopping more frequently at supermarkets were more likely to have greater vegetable and fiber intake (OR 1.26; 1.06-1.50; OR 1.28; 1.03-1.58, respectively). Also, youth with parents who shopped more frequently at fast-food stores had 7 % lower odds for higher vegetable intake (95 % CI: 0.88-0.99). CONCLUSION: In this study, both, youth and household factors were associated with youth FV and fiber intake, underscoring the need for a multi-level approach to increasing youths' diet quality. These results will inform and shape an effective intervention program for improving youth dietary intakes. PMID- 27558164 TI - First report of tertiary syphilis presenting as lipoatrophic panniculitis in an immunocompetent patient. AB - We describe herein a woman who developed subcutaneous gummas in her trochanteric regions, bilaterally, although she had been treated for syphilis two decades earlier. Evidence of Treponema pallidum latent late infection was the presence of IgG antibodies against T. pallidum and the positive non-treponemal and treponemal tests. Moreover, immunohistochemical staining for T. pallidum detected some spirochetes close to the atrophic adipocytes allowing the diagnosis of lypo atrophic panniculitis tertiary syphilis. This is the first case of tertiary syphilis presenting as panniculitis in an immunocompetent patient, demonstrating that subcutaneous fat may be another organ infected in tertiary syphilis. PMID- 27558165 TI - Autophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization. AB - One of the major defense mechanisms against virus spread in vivo is the blocking of viral infectibility by neutralizing antibodies. We describe here the identification of infectious autophagy-associated dengue vesicles released from infected cells. These vesicles contain viral proteins E, NS1, prM/M, and viral RNA, as well as host lipid droplets and LC3-II, an autophagy marker. The viral RNA can be protected within the autophagic organelles since anti-dengue neutralizing antibodies do not have an effect on the vesicle-mediated transmission that is able to initiate a new round of infection in target cells. Importantly, such infectious vesicles were also detected in a patient serum. Our study suggests that autophagy machinery plays a new role in dengue virus transmission. This discovery explains the inefficiency of neutralizing antibody upon dengue infection as a potential immune evasion mechanism in vivo. PMID- 27558166 TI - Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line. AB - BACKGROUND: Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract (AMCE) on breast cancer cell lines were evaluated. METHODS: A screening of nineteen samples of Annona muricata from different location was determined by MTT assay on breast cancer cell lines (MCF-7, MDA-MB 231, and 4 T1) which revealed a varied potency (IC50) amongst them. Then, based on the IC50 profile from the anti-proliferative assay, further downward assays such as cell cycle analysis, Annexin V/FITC, AO/PI, migration, invasion, and wound healing assay were performed only with the most potent leaf aqueous extract (B1 AMCE) on 4 T1 breast cancer cell line to investigate its anti-cancer effect. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor. At the end of the experiment, histopathology of tumor section, tumor nitric oxide level, tumor malondialdehyde level, clonogenic assay, T cell immunophenotyping, and proteome profiler analysis were performed. RESULTS: Annona muricata crude extract samples exhibited different level of cytotoxicity toward breast cancer cell lines. The selected B1 AMCE reduced the tumor's size and weight, showed anti-metastatic features, and induced apoptosis in vitro and in vivo of the 4 T1 cells. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population. CONCLUSION: The results suggest that, B1 AMCE is a promising candidate for cancer treatment especially in breast cancer and deserves further research as an alternative to conventional drugs while also stressed out the selection of soursop sample which plays a significant role in determining its potential therapeutic effect on cancer. PMID- 27558167 TI - A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma. AB - Circulating microRNAs (miRNAs) hold great promise as novel clinically blood-based biomarkers for cancer diagnosis and prognosis. However, little is known about their impact in meningioma. The TLDA assay was performed as an initial survey to determine the serum miRNA expression profile in two pooled samples from 20 pre operative meningiomas and 20 matched healthy controls. Selected candidate miRNAs were subsequently validated individually in another 210 patients and 210 healthy controls from two independent cohorts by qRT-PCR. The serum levels of miR-106a 5p, miR-219-5p, miR-375, and miR-409-3p were significantly increased, whereas the serum levels of miR-197 and miR-224 were markedly decreased. The area under the ROC curve (AUC) for the six combined miRNAs was 0.778. The 4 increased miRNAs were significantly decreased, while the 2 decreased miRNAs were significantly increased after tumor removal. Furthermore, the expression levels of miR-224 were associated with sex, and the expression levels of miR-219-5p were positively associated with the clinical stages of meningioma. Finally, the high expression of miR-409-3p and low expression of miR-224 were significantly correlated with higher recurrence rates. The present study revealed that the panel of 6 serum miRNA may have the potential to be used clinically as an auxiliary tool for meningioma patients. PMID- 27558168 TI - Lipid lowering activity of novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats. AB - CONTEXT: Dyslipidemia is a major risk factor for the development of cardiovascular diseases. Many dyslipidemic patients do not achieve their target lipid levels with the currently available medications, and most of them may experience many side effects. OBJECTIVE: The present work aimed toward identifying a new class of novel nicotinic acid-carboxamide derivatives as promising antihyperlipidemic compounds. MATERIALS AND METHODS: Six novel N (benzoylphenyl)pyridine-3-carboxamide derivatives were synthesized using acid chloride pathways. All structures were confirmed using 1H-NMR, 13C-NMR, IR, and HRMS. The evaluation of biological activity was conducted using Triton WR-1339 induced hyperlipidemic rats model. RESULTS: This study revealed that some of the newly synthesized novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives mainly C4 and C6 possessed significant antihyperlipidemic activities on lipid components TG and TC (p value <0.05). DISCUSSION AND CONCLUSION: This research opens the door for new potential antihyperlipidemic compounds derived from nicotinic acid that need further optimization of their biological activities. PMID- 27558169 TI - Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time. AB - Prion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrPC ) into a misfolded isoform (PrPSc ) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases; however, their impact on prion disease pathophysiology is unclear with both beneficial PrPSc -clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology. Here, the degree of microglia activation in the brain of prion infected mice with and without an additional intraperitoneal retrovirus infection was studied. Peripheral murine retrovirus infection leads to activation of parenchymal microglia without recruitment of monocytes. This activation correlated with transient clearance or delay in accumulation of infectious prions specifically from the brain at early time points in the diseases course. Microglia expression profiling showed upregulation of genes involved in protein degradation coinciding with prion clearance. This enforces a concept where microglia act beneficial in prion disease if adequately activated. Once microglia activation has ceased, prion disease reemerges leading to disease kinetics undistinguishable from the situation in prion-only infected mice. This might be caused by the loss of microglial homeostatic function at clinical prion disease. PMID- 27558170 TI - Soy Pulp Extract Inhibits Angiotensin I-Converting Enzyme (ACE) Activity In Vitro: Evidence for Its Potential Hypertension-Improving Action. AB - Soy pulp, called "okara" in Japanese, is known as a by-product of the production of bean curd (tofu), and expected to contain a variety of biologically active substances derived from soybean. However, the biological activities of okara ingredients have not yet been fully understood, and the effectiveness of okara as a functional food seems necessary to be further evaluated. Then the effect of okara extract on angiotensin I-converting enzyme (ACE) activity was examined in vitro, and the extract was shown to cause the inhibition of ACE activity in a manner depending on its concentration. Kinetic analysis indicated that this enzyme inhibition was accompanied by an increase in the Km value without any change in Vmax. Further studies suggested that putative inhibitory substances contained in the extract might be heat stable and dialyzable, and recovered mostly in the peptide fraction obtained by a spin-column separation and a high performance liquid chromatography (HPLC) fractionation. Therefore, the extract was speculated to contain small-size peptides responsible for the inhibitory effect of okara extract on ACE activity, and could be expected to improve the hypertensive conditions by reducing the production of hypertensive peptide. PMID- 27558172 TI - A multiplex allele-specific real-time polymerase chain reaction assay for HLA B*13:01 genotyping in four Chinese populations. AB - Human leukocyte antigen HLA-B*13:01 is identified currently as a marker of individual susceptibility to drug-induced hypersensitivity reaction, such as dapsone-induced hypersensitivity reactions (DIHRs) and trichloroethylene-induced dermatitis. Therefore, screening for the HLA-B*13:01 allele can assist clinics in identifying patients at risk of developing DIHRs. By combining the allele specific primers with TaqMan probes, we established a single tube, triplex real time PCR to detect HLA-B*13:01. The reliability of this assay was validated by the comparison of genotyping results with those by sequence-based typing (SBT). With this assay, the distribution of HLA-B*13:01 in a total of 350 blood samples from four ethnic groups: Han, Tibetan, Uighur, and Buyei were determined. A 100% concordance was observed between the results with the established real-time PCR and SBT in 100 samples. The detection limit of this assay was 0.016 ng genomic DNA. The prevalence of HLA-B*13:01 carriers were 11%, 8%, 1%, and 2% in the Buyei (n = 100), Northern Han (n = 100), Tibetan (n = 100), and Uighur (n = 50) populations, respectively. The multiplex real-time PCR assay provided a fast and reliable method for accurate detection of HLA-B*13:01 allele prior to dapsone administration in clinical practice and onset of the reaction after exposure to trichloroethylene. PMID- 27558171 TI - Smokeless tobacco and oral potentially malignant disorders in South Asia: a protocol for a systematic review. AB - INTRODUCTION: Oral potentially malignant disorders (OPMDs) are chronic lesions or conditions characterized by a potential for malignant transformation. Apart from being possible pre-cursors to oral cancer, OPMDs themselves are usually painful and debilitating conditions having an influence on the quality of life, both in terms of pain and social disability. Smokeless tobacco (SLT) use is considered a major risk factor for OPMDs. SLT use is a culturally and socially acceptable habit in South Asia. According to a recent report, 90 % of the SLT burden of the whole world lies in the South Asian countries of Pakistan, India, Sri Lanka, Bangladesh, Bhutan, Nepal, Afghanistan, and Maldives. This review aims to assess the association between the use of various SLT products in South Asia and risk of OPMDs. METHODS: This review will focus on epidemiological studies on the use of SLT and risk modification for OPMDs, which have been carried out in the human population of South Asian countries. Articles reporting estimates of relative risk, e.g., odds ratio (OR) or relative risk (RR) with their 95 % confidence intervals (CI) for SLT users versus non-users. Articles reporting data from which these effect estimates can be computed will be included in the review. We will search MEDLINE, the Science Citation Index (SCI), Scopus, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for relevant literature using a combination of keywords and MeSH terms, where applicable. Appropriate sources of gray literature will also be included in the search. The electronic searches will be supplemented by a hand search of the bibliographies of the included articles. The included studies will be assessed for their quality using an established quality assessment tool. All relevant data from the included articles will be recorded in an MS Excel spread sheet and then transferred to Rev Man 5.3 to carry out a meta-analysis. Heterogeneity among the estimates will be assessed through the I (2) statistic. Sensitivity and subgroup analysis will be carried out to see the effects of individual or group of studies on the pooled effect estimate. Results of the review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. DISCUSSION: This review may have a potential limitation with regard to the designs of the studies included as we expect that most of the included studies will be of the observational types. We will however try to address this issue by conducting sensitivity and subgroup analysis of similar quality studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029705 . PMID- 27558173 TI - Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy. AB - Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease. PMID- 27558174 TI - End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics. AB - BACKGROUND: End-inspiratory pause (EIP) prolongation decreases dead space-to tidal volume ratio (Vd/Vt) and PaCO2. We do not know the physiological benefits of this approach to improve respiratory system mechanics in acute respiratory distress syndrome (ARDS) patients when mild hypercapnia is of no concern. METHODS: The investigation was conducted in an intensive care unit of a university hospital, and 13 ARDS patients were included. The study was designed in three phases. First phase, baseline measurements were taken. Second phase, the EIP was prolonged until one of the following was achieved: (1) EIP of 0.7 s; (2) intrinsic positive end-expiratory pressure >=1 cmH2O; or (3) inspiratory expiratory ratio 1:1. Third phase, the Vt was decreased (30 mL every 30 min) until PaCO2 equal to baseline was reached. FiO2, PEEP, airflow and respiratory rate were kept constant. RESULTS: EIP was prolonged from 0.12 +/- 0.04 to 0.7 s in all patients. This decreased the Vd/Vt and PaCO2 (0.70 +/- 0.07 to 0.64 +/- 0.08, p < 0.001 and 54 +/- 9 to 50 +/- 8 mmHg, p = 0.001, respectively). In the third phase, the decrease in Vt (from 6.3 +/- 0.8 to 5.6 +/- 0.8 mL/Kg PBW, p < 0.001) allowed to decrease plateau pressure and driving pressure (24 +/- 3 to 22 +/- 3 cmH2O, p < 0.001 and 13.4 +/- 3.6 to 10.9 +/- 3.1 cmH2O, p < 0.001, respectively) and increased respiratory system compliance from 29 +/- 9 to 32 +/- 11 mL/cmH2O (p = 0.001). PaO2 did not significantly change. CONCLUSIONS: Prolonging EIP allowed a significant decrease in Vt without changes in PaCO2 in passively ventilated ARDS patients. This produced a significant decrease in plateau pressure and driving pressure and significantly increased respiratory system compliance, which suggests less overdistension and less dynamic strain. PMID- 27558175 TI - Investments in tuberculosis research - what are the gaps? AB - Through decades of research, numerous studies have generated robust evidence about effective interventions for tuberculosis control. Yet, the global annual decline in incidence of approximately 1 % is evidence that current approaches and investment strategies are not sufficient. In this article, we assess recent tuberculosis research funding and discuss two critical gaps in funding and in scientific evidence from topics that have been left off the research priority agenda.We first examine research and development funding goals in the 2011-2015 Global Plan to Stop Tuberculosis and analyze disbursements to different research areas by funders worldwide in 2014. We then summarize, through a compilation of published literature and consultation with 35 researchers across multiple disciplines in the London School of Hygiene and Tropical Medicine TB Centre, priorities identified by the tuberculosis research community. Finally, we compare researchers' priority areas to the global funding agendas and activities.Our analysis shows that, among the five key research areas defined in the 2011-2015 Global Plan - namely drugs, basic science, vaccines, diagnostics and operational research - drug discovery and basic science on Mycobacterium tuberculosis accounted for 60 % of the $2 billion annual funding target. None of the research areas received the recommended level of funding. Operational research, which had the lowest target, received 66 % of its target funding, whereas new diagnostics received only 19 %. Although many of the priority research questions identified by researchers fell within the Global Plan categories, our analysis highlights important areas that are not explicitly mentioned in the current plan. These priority research areas included improved understanding of tuberculosis transmission dynamics, the role of social protection and social determinants, and health systems and policy research.While research priorities are increasingly important in light of the limited funding for tuberculosis, there is a risk that we neglect important research areas and encourage the formation of research silos. To ensure that funding priorities, researchers' agendas and national tuberculosis control policies are better coordinated, there should be more, and wider, dialogue between stakeholders in high tuberculosis burden countries, researchers, international policymakers and funders. PMID- 27558176 TI - Rapid Antimicrobial Susceptibility Testing Using Forward Laser Light Scatter Technology. AB - The delayed reporting of antimicrobial susceptibility testing remains a limiting factor in clinical decision-making in the treatment of bacterial infection. This study evaluates the use of forward laser light scatter (FLLS) to measure bacterial growth for the early determination of antimicrobial susceptibility. Three isolates each (two clinical isolates and one reference strain) of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were tested in triplicate using two commercial antimicrobial testing systems, the Vitek2 and the MicroScan MIC panel, to challenge the BacterioScan FLLS. The BacterioScan FLLS showed a high degree of categorical concordance with the commercial methods. Pairwise comparison with each commercial system serving as a reference standard showed 88.9% agreement with MicroScan (two minor errors) and 72.2% agreement with Vitek (five minor errors). FLLS using the BacterioScan system shows promise as a novel method for the rapid and accurate determination of antimicrobial susceptibility. PMID- 27558177 TI - Pooled Nucleic Acid Amplification Test for Screening of Stool Specimens for Shiga Toxin-Producing Escherichia coli. AB - Shiga toxin-producing Escherichia coli (STEC)-associated enteric illness is attributed to O157 and non-O157 serotypes; however, traditional culture-based methods underdetect non-O157 STEC. Labor and cost of consumables are major barriers to implementation of the CDC recommendation to test all stools for both O157 and non-O157 serotypes. We evaluated the feasibility of a pooled nucleic acid amplification test (NAAT) as an approach for screening stool specimens for STEC. For retrospective evaluation, 300 stool specimens were used to create pools of 10 samples each. The sensitivity was 83% for the preenrichment pooling strategy and 100% for the postenrichment pooling strategy compared with those for individual NAAT results. The difference in cycle threshold (CT) between individual and pooled NAAT results for specimens was significantly lower and more consistent for postenrichment pooling (stx1 mean = 3.90, stx2 mean = 4.28) than those for preenrichment pooling (excluding undetected specimens; stx1 mean = 9.34, stx2 mean = 8.96) (P <= 0.0013). Cost of consumables and labor time savings of 48 to 81% and 6 to 66%, respectively, were estimated for the testing of 90 specimens by the postenrichment pooled NAAT strategy on the basis of an expected 1 to 2% positivity rate. A 30-day prospective head-to-head clinical trial involving 512 specimens confirmed the sensitivity and labor savings associated with the postenrichment pooled NAAT strategy. The postenrichment pooled NAAT strategy described here is suitable for efficient large-scale surveillance of all STEC serotypes. Comprehensive detection of STEC will result in accurate estimation of STEC burden and, consequently, appropriate public health interventions. PMID- 27558178 TI - Real-Time Genome Sequencing of Resistant Bacteria Provides Precision Infection Control in an Institutional Setting. AB - The increasing prevalence of multidrug-resistant (MDR) bacteria is a serious global challenge. Here, we studied prospectively whether bacterial whole-genome sequencing (WGS) for real-time MDR surveillance is technical feasible, returns actionable results, and is cost-beneficial. WGS was applied to all MDR isolates of four species (methicillin-resistant Staphylococcus aureus [MRSA], vancomycin resistant Enterococcus faecium, MDR Escherichia coli, and MDR Pseudomonas aeruginosa) at the University Hospital Muenster, Muenster, Germany, a tertiary care hospital with 1,450 beds, during two 6-month intervals. Turnaround times (TAT) were measured, and total costs for sequencing per isolate were calculated. After cancelling prior policies of preemptive isolation of patients harboring certain Gram-negative MDR bacteria in risk areas, the second interval was conducted. During interval I, 645 bacterial isolates were sequenced. From culture, TATs ranged from 4.4 to 5.3 days, and costs were ?202.49 per isolate. During interval II, 550 bacterial isolates were sequenced. Hospital-wide transmission rates of the two most common species (MRSA and MDR E. coli) were low during interval I (5.8% and 2.3%, respectively) and interval II (4.3% and 5.0%, respectively). Cancellation of isolation of patients infected with non-pan resistant MDR E. coli in risk wards did not increase transmission. Comparing sequencing costs with avoided costs mostly due to fewer blocked beds during interval II, we saved in excess of ?200,000. Real-time microbial WGS in our institution was feasible, produced precise actionable results, helped us to monitor transmission rates that remained low following a modification in isolation procedures, and ultimately saved costs. PMID- 27558179 TI - Cerebrospinal Fluid (1,3)-Beta-d-Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis. AB - Diagnosing coccidioidal meningitis (CM) can be problematic owing to its infrequency and/or a delay in the positivity of a cerebrospinal fluid (CSF) culture or CSF antibody, particularly if the primary coccidioidal infection is unrecognized. We tested 37 CSF specimens, 26 from patients with confirmed CM and 11 from patients with suspected microbial meningitis without fungal diagnosis, for (1,3)-beta-glucan (BG). BG in CM CSF specimens ranged from 18 to 3,300 pg/ml and in controls ranged from <3.9 to 103 pg/ml. Diagnostic performance was determined using a 31-pg/ml cutoff (the bottom of the serum range according to the directions for the commercial kit, although further serial dilutions of the standard indicated linearity to 3.9). Sensitivity was 96%, specificity was 82%, positive and negative predictive values were 93% and 90%, and the area under the receiver operating characteristic curve was 0.937. Fifteen of 15 samples of >103 pg/ml were CM. The one false-negative specimen was from a patient with a pseudosyrinx, without inflammatory evidence of meningitis activity. Serial samples from some patients were positive at <=8 years, indicating no loss of positivity with chronicity. Samples stored frozen since 2000 included those with 2 of the 3 highest values, indicating that fresh samples not required. A previous study indicated serum sensitivities of 53% in acute, 50% in resolved, and 83% in disseminated and meningeal coccidioidomycosis. Three studies of other fungal meningitides ranged from 86 to 1,524 pg/ml CSF, with 37 controls of <4 to 115 pg/ml CSF. CSF BG analysis had good diagnostic performance in CM. CSF BG testing can be useful in CM, and a commercial kit is available. It will be of interest to correlate this with course, treatment, outcome, inflammation, and antigen. The only mycoses with common central nervous system (CNS) involvement are cryptococcal and coccidioidal, so CSF BG screening can be useful in meningitis diagnosis. PMID- 27558180 TI - Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial. AB - Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 MUg/ml), and 5/814 (0.6%) carried qacA or qacB At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution. PMID- 27558181 TI - Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection. AB - Clostridium difficile (Peptoclostridium difficile) is a common health care associated infection with a disproportionately high incidence in elderly patients. Disease symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. Around 20% of patients may suffer recurrent disease, which often requires rehospitalization of patients. C. difficile was isolated from stool samples from a patient with two recurrent C. difficile infections. PCR ribotyping, whole-genome sequencing, and phenotypic assays were used to characterize these isolates. Genotypic and phenotypic screening of C. difficile isolates revealed multiple PCR ribotypes present and the emergence of rifamycin resistance during the infection cycle. Understanding both the clinical and bacterial factors that contribute to the course of recurrent infection could inform strategies to reduce recurrence. (This study has been registered at ClinicalTrials.gov under registration no. NCT01670149.). PMID- 27558182 TI - Molecular Characteristics of Group B Streptococci Isolated from Adults with Invasive Infections in Japan. AB - Streptococcus agalactiae (group B streptococcus) isolates (n = 443) obtained from Japanese adults with invasive infections between April 2010 and March 2013 were analyzed for capsular serotype, multilocus sequence type (ST), antibiotic susceptibility, and resistance genes. Among these cases, bacteremia without primary focus was the most common variety of infection (49.9%), followed by cellulitis (12.9%) and pneumonia (9.0%). Concerning patient age (18 to 59, 60 to 69, 70 to 79, 80 to 89, and 90 years old or older), the incidence of pneumonia increased in patients in their 70s and 80s (P < 0.001), while younger patients (18 to 59 and 60 to 69 years old) were more likely to have abscesses (P < 0.05). The mortality rate was 10.2% for all ages. The most common capsular serotype was Ib (39.5%), followed by V (16.0%), III (13.8%), VI (9.5%), and Ia (8.6%). The main ST of serotype Ib strains was ST10, which belonged to clonal complex 10 (88.0%). The predominant clonal complexes of serotypes V and III, respectively, were 1 (78.9%) and 19 (75.4%). Among these isolates, 9 strains (2.0%) were identified as group B streptococci with reduced penicillin susceptibility, reflecting amino acid substitutions in penicillin-binding protein 2X (PBP2X). In addition, 19.2% of all strains possessed mef(A/E), erm(A), or erm(B) genes, which mediate macrolide resistance, while 40.2% of strains were resistant to quinolones resulting from amino acid substitutions in GyrA and ParC. Our data argue strongly for the continuous surveillance of microbial characteristics and judicious antibiotic use in clinical practice. PMID- 27558183 TI - Lyme Borreliosis Serology: Performance of Several Commonly Used Laboratory Diagnostic Tests and a Large Resource Panel of Well-Characterized Patient Samples. AB - The current recommendation for the laboratory confirmation of Lyme disease is serology-based diagnostics. Specifically, a standardized two-tiered testing (STTT) algorithm is applied that utilizes a first-tier immunofluorescence assay or enzyme immunoassay (EIA) that, if the result is positive or equivocal, is followed by second-tier immunoblotting. Despite the standardization and performance achievements, STTT is considered technically complex and subjective, as well as insensitive for early acute infection. These issues have prompted development of novel algorithms and testing platforms. In this study, we evaluated the performance of several commonly used assays for STTT. Several modified two-tiered testing (MTTT) algorithms, including a 2-EIA algorithm and modified criteria for second-tier IgG immunoblots, were also evaluated. All tests were performed on sera from a recently available, well-defined archive of positive- and negative-control patients. Our study demonstrates differences in the results between individual first- and second-tier tests, although the overall agreement of the different STTT algorithms used was strong. In addition, the MTTT algorithm utilizing 2-EIAs was found to be equivalent to all STTT algorithms tested, with agreement ranging from 94 to 97%. The 2-EIA MTTT algorithm slightly enhanced sensitivity in early disease compared to the STTT algorithms evaluated. Furthermore, these data add to the mounting evidence that a 2-EIA-based MTTT algorithm, where immunoblotting is replaced by the C6 EIA, performs as well or better than STTT. PMID- 27558185 TI - Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization. AB - Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90 degrees ) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the alpha carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds. PMID- 27558184 TI - Accurate Detection of Avian Respiratory Viruses by Use of Multiplex PCR-Based Luminex Suspension Microarray Assay. AB - A novel oligonucleotide suspension microarray (Luminex microsphere system) was developed for the rapid detection of avian respiratory viruses of major clinical importance. This test was optimized and validated with 70 clinical samples. The developed tool was accurate for high-throughput detection and differentiation of the most important avian respiratory viruses: avian influenza virus (AIV), Newcastle disease virus (NDV), infection bronchitis virus (IBV), and infectious laryngotracheitis virus (ILTV) in single- and mixed-virus infections. A multiplex reverse transcriptase PCR (RT-PCR), followed by a monoplex or a multiplex Luminex assays, were realized using a Luminex 200 analyzer instrument. The sensitivity, specificity, and reproducibility of the multiplex DNA suspension microarray system were evaluated. The results showed no significant differences in the median fluorescence intensity (MFI) value in monoplex and multiplex Luminex assays. The sensitivity and specificity proved to be completely concordant with monoplex real-time RT-PCR. We demonstrated that the multiplex DNA suspension microarray system is an accurate, high-throughput, and relatively simple method for the rapid detection of the main respiratory viruses of poultry. PMID- 27558186 TI - Effects of acute androstenedione supplementation on testosterone levels in older men. AB - The purpose of the study was to examine the effects of acute androstenedione supplementation on hormone levels in older men at rest and during exercise. Men (n = 11) between the ages of 58 and 69 were divided into an experimental (n = 6; 62.33 +/- 2.57 y) and control (n = 5; 60.2 +/- 1.02 y) groups. Each participant received an oral 300 mg dose of either androstenedione (experimental) or a cellulose placebo (control) for 7 d. Pre- and post-supplementation participants completed two separate, 20-min strength tasks consisting of leg extension and leg curls at different percentages of their 10-RM. Researchers collected blood samples pre-, during, and post-exercise. Blood samples were analyzed for testosterone, androstenedione, and estradiol levels. The researchers found a significant difference between pre- (4.36 +/- 56 ng/mL) and post- (5.51 +/- 0.35 ng/mL) testosterone levels, as well as pre- (0.88 +/- 0.20) and post- (7.46 +/- 1.25) androstenedione levels, but no significant differences between pre- and post-estradiol levels for either group. It appears that short-term androstenedione supplementation augmented acute testosterone responses to resistance exercise in older men. However, further study of this supplement is needed to determine any potential it may have in mitigating andropause. PMID- 27558187 TI - Severe hyponatraemia associated with pre-eclampsia. AB - Pre-eclampsia is a multisystem disorder with incidence rates ranging from 2% to 5%. Hyponatraemia is a rare complication of pre-eclampsia. A 41-year-old, para 0+1 in vitro fertilisation monochorionic diamniotic triplet pregnancy woman presented at 25 weeks with dyspnoea and general malaise. Her antenatal course was complicated by the diagnosis of intrauterine growth restriction in triplet one at 27 weeks of gestation. At 27+3 weeks gestation, she was diagnosed as having pre eclampsia. Subsequent biochemical analysis demonstrated hyponatraemia with serum sodium falling steadily to 117 mmol/L over the next 19 days. She was admitted to intensive care unit for stabilisation of fulminant pre-eclampsia and severe hyponatraemia at 30+5 weeks of gestation. Hypertonic saline and intravenous labetolol were administered prior to delivery by caesarean section. She recovered well postdelivery with stabilisation of her blood pressure and normalisation of her sodium level to 135 mmol/L. Awareness and frequent monitoring of hyponatraemia should become an integral part of monitoring women with pre eclampsia. PMID- 27558188 TI - Congenital tufting enteropathy and chronic arthritis: a clinical and radiological perspective. AB - Congenital tufting enteropathy is a rare condition which presents in early infancy. It is a condition which should be suspected in infants who present with diarrhoea soon after birth. A rare association with arthritis has been observed with a handful of cases documented in the literature. Our case differs as the arthritis described is erosive in nature, a feature which is not present in other cases. PMID- 27558189 TI - Barr humbug: acute cerebellar ataxia due to Epstein-Barr virus. AB - Epstein-Barr virus (EBV) infection is associated with neurological sequellae, but rarely there is acute cerebellar ataxia (ACA) in an adult. We present a novel case of a 26-year-old man, who presented with ACA. He had normal MRI and CSF analysis. Serum testing confirmed active EBV. A course of oral prednisolone 1 mg/kg for 4 weeks, with a subsequent taper was started. He made a full recovery within 3 weeks of presentation. PMID- 27558190 TI - Spontaneous coronary artery dissection as the first presentation of systemic lupus erythematosus. AB - A 33-year-old woman with no premorbidities presented to us with chest pain and worsening dyspnoea since 1 week. Systemic examination was suggestive of acute pulmonary oedema and preliminary investigations revealed evolved anterior wall myocardial infarction (MI). The patient was stabilised and taken up for angiography which revealed spontaneous coronary artery dissection (SCAD) of the left anterior descending (LAD) artery. She underwent percutaneous coronary intervention (PCI) for the same. Further investigation into the cause for the SCAD came strongly positive for systemic lupus erythematosus (SLE). She had no prior symptoms suggestive of SLE and the SCAD was its very first clinical manifestation. PMID- 27558191 TI - Case of gastric intestinal metaplasia in an old patient with previous gastric surgery. AB - An 87-year-old woman with multiple medical disorders presented with dyspeptic symptoms of long duration. She has a history of peptic ulcer disease for which she has partial gastrectomy (Billroth I) in the past. Oesophagogastroduodenoscopy (OGD) was performed which revealed erythematous mucosa in the lower part of the gastric remnant with areas of whitish mucosal patches in the distal stomach close to the gastroduodenal anastomosis. Biopsies were taken from the whitish mucosal patches and sent for histopathological examination. The result of the biopsy confirmed the presence of marked intestinal metaplasia. This case report summarises the presentation, diagnoses and treatment of gastric intestinal metaplasia (GIM). PMID- 27558192 TI - Necrotizing granulomatous inflammation of the glans penis. AB - We describe the case of a 73-year-old man who presented with a 10-month history of an ulcerating lesion on the glans penis. Initially this was thought to be an invasive squamous cell carcinoma but a biopsy showed histological features consistent with necrotizing granulomatous inflammation. Extensive serological, immunological and microbiological tests only showed a positive antinuclear and perinuclear antineutrophil cytoplasmic antibodies indicating a possible autoimmune aetiology but an underlying systemic cause was not identified. Treatment with oral corticosteroids limited the inflammatory process but due to the gross destruction of the glans penis, he still required a glansectomy and split-skin graft reconstruction from which he recovered well. Although this patient ultimately required surgery for this rare presentation, this case highlights the differential diagnosis of penile ulceration (that transcends neoplasia) and the importance of performing and interpreting penile biopsies before undertaking potentially mutilating definitive surgery. PMID- 27558193 TI - Nodular rheumatoid arthritis resembling gout. PMID- 27558194 TI - Anterior segment optical coherence tomography of silicone oil keratopathy. PMID- 27558195 TI - Left pleural effusion caused by pancreaticopleural fistula with a pancreatic pseudocyst. AB - Pancreaticopleural fistula is an uncommon complication of chronic pancreatitis. The authors described a case of a man with medical history of alcohol-related chronic pancreatitis, presented with dyspnoea. The roentgenogram showed a massive left pleural effusion. Additional work-up revealed a pancreaticopleural fistula and amylase-rich pleural effusion. His respiratory state improved after the insertion of chest drainage tube. During his admission, conservative and endoscopic therapy was required for the treatment of his complication of mediastinal abscess and arterial aneurysm in the pancreatic pseudocyst. PMID- 27558196 TI - One-Pot To Synthesize Multifunctional Carbon Dots for Near Infrared Fluorescence Imaging and Photothermal Cancer Therapy. AB - It is an emerging focus to develop a simple and straightforward strategy to synthesize multifunctional nanomedicines for cancer imaging and treatment. In this work, a new carbon dot (named CyCD) with intrinsic theranostic properties was prepared from a hydrophobic cyanine dye [2-((E)-2-((E)-2-chloro-3-((E)-2-(1 (2-hydroxyethyl)-3,3-dimethylindolin-2-ylidene) ethylidene)cyclohex-1-en-1 yl)vinyl)-1-(2-hydroxyethyl)-3,3-dimethyl-3H-indol-1-ium iodide, CyOH] and poly(ethylene glycol) (PEG800) via a simple solvothermal process. The as-prepared CyCD is well dispersed in water media with an average diameter of 2.9 +/- 0.5 nm; it possesses favorable hydrophilicity and excellent photostability. More importantly, the strong absorption and near-IR (NIR) emission within the range from 600 to 900 nm, along with preferential uptake at tumors and high photothermal conversion efficiency (eta = 38.7%), facilitate CyCD to act as an ideal theranostic agent for NIR fluorescent imaging and photothermal therapy in vitro and in vivo. This work highlights theranostic CDs as an excellent candidate for efficient cancer imaging and therapy. PMID- 27558197 TI - Membrane-associated guanylate kinase scaffolds organize a horizontal cell synaptic complex restricted to invaginating contacts with photoreceptors. AB - Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. Because each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in the tips of B-type horizontal cell processes, where they contact cone and rod photoreceptors. We further identified some known SAP102 binding partners, kainate receptor GluR6/7 and inward rectifier potassium channel Kir2.1, closely associated with SAP102 in photoreceptor invaginations. The kainate receptor occupies a position distinct from that of the majority of AMPA receptors that dominate the horizontal cell postsynaptic response. GluR6/7 and Kir2.1 presumably are involved in synaptic processes that govern cell-to-cell communication and could both contribute in different ways to synaptic currents that mediate feedback signaling. Notably, we failed to find evidence for the presence of Cx57 or Cx59 that might be involved in ephaptic feedback signaling in this complex. The presence of SAP102 and its binding partners in both cone and rod invaginating synapses suggests that whatever mechanism is supported by this protein complex is present in both types of photoreceptors. J. Comp. Neurol. 525:850-867, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27558198 TI - Clinical course and short-term mortality of cirrhotic patients with infections other than spontaneous bacterial peritonitis. AB - BACKGROUND & AIMS: Clinical course and risk factors of death in non-spontaneous bacterial peritonitis (SBP) infections are poorly known. We assessed the prevalence of acute kidney injury (AKI) and type-1 hepatorenal syndrome (HRS), hospital, 30-day and 90-day mortality and risk factors of death in 441 decompensated patients. METHODS: Analysis of 615 non-SBP infections (161 urinary infections (UTI), 95 cellulitis, 92 suspected infections, 92 bacteraemias, 84 pneumonias, 21 bronchitis, 18 cholangitis, 15 spontaneous empyema, 13 secondary peritonitis, 24 other). RESULTS: Ninety-six percent of infections solved. AKI and type-1 HRS were developed in 37% and 9% of infections respectively. Overall hospital, 30-day and 90-day mortality rates were 11%, 12% and 18% respectively. Clinical course and mortality differed markedly across infections. Endocarditis, osteoarticular infections, pneumonia, spontaneous bacteraemia, cholangitis, secondary peritonitis and UTI showed higher rates of AKI. Prevalence of type-1 HRS was not significantly different among infections. Endocarditis, secondary peritonitis, pneumonia and bacteraemia showed lower rates of renal impairment resolution and higher hospital mortality associated with AKI (42% vs 12%, P<.0001) or type-1 HRS (71% vs 27%, P=.003) than the rest of infections. Age (HR: 1.04), serum sodium (HR: 0.91), serum bilirubin (HR: 1.06), INR (HR: 1.91), hepatic encephalopathy (HR: 2.44), ascites (HR: 3.06) and multidrug-resistant isolation (HR: 2.27) at infection diagnosis were independent predictors of death during hospitalization. CONCLUSIONS: Non-SBP infections constitute a heterogeneous group regarding clinical course and prognosis. Endocarditis, secondary peritonitis, pneumonia and bacteraemia show worse prognosis. The combination of data of liver and renal dysfunction and of the type of infection allows the identification of patients with poor prognosis. PMID- 27558200 TI - Selective 5-HT7 Receptor Activation May Enhance Synaptic Plasticity Through N methyl-D-aspartate (NMDA) Receptor Activity in the Visual Cortex. AB - Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that modulates N-methyl-D-aspartate (NMDA) receptor activity by binding to several different 5-HT receptor subtypes. In the present study, we used whole-cell patch clamp recordings in transverse slice preparations to test the role of 5-HT receptors in modulating the NMDA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer II/III pyramidal neurons of the rat visual cortex. We found that the NMDA receptor-mediated component of mEPSCs could be potentiated by exogenously applied 5-HT. Similar results were obtained by exogenously applied 5-CT or 8-OH-DPAT (the 5-HT1A and 5-HT7 receptor agonist). A specific antagonist for the 5-HT7 receptor, SB-269970, completely blocked the increase in NMDA receptor-mediated component of mEPSCs by 5-CT or 8- OH-DPAT. Moreover, the selective 5-HT1A receptor antagonist, WAY-100135, displayed no influence on the enhancement in NMDA receptor-mediated component of mEPSCs by 5-CT or 8-OHDPAT. These results indicated that the increase in NMDA receptor-mediated component of mEPSCs by 5-HT in layer II/III pyramidal neurons of the young rat visual cortex requires activation of 5-HT7 receptors, but not 5-HT1A receptors. These observations might be clinically relevant to schizophrenia and Alzheimer's disease (AD), where enhancing NMDA receptor-mediated neurotransmission is considered to be a promising strategy for treatment of these diseases. PMID- 27558199 TI - Effectiveness of a secondary prevention protocol for occupational contact dermatitis. AB - BACKGROUND: Occupational skin diseases are often responsible for sick leave or job changes, affect mostly young subjects, are costly to society and have been reported as significant predictor of unemployment. OBJECTIVES: To assess, over time, the course of occupational hand dermatitis (OHD) after a specific training, by means of follow-up visits and TEWL measurement, to evaluate skin barrier integrity and if preventive measures for hand skin care provided may influence the course of the disease. METHODS: Workers with a diagnosis of OHD from January 2011 to December 2013 were contacted by telephone, filled in a questionnaire (NOSQ-2002) and were invited to a training course on prevention of skin dermatitis, and to a new clinical evaluation with TEWL measurement. Workers who joined the training programme were asked to undergo a new evaluation after 3 months. A total of 65 subjects without contact dermatitis were recruited as control group. RESULTS: One hundred and one subjects from 143 workers, who were contacted, filled in the questionnaire. Sixty-five of them followed the training course and underwent a new clinical evaluation withTEWL measurements. Ongoing symptoms of subjects decreased from 60.0% to 42.3% 3 months after the training, and the subgroup which strictly adhered to the recommendations given achieved better results (61.9% of symptoms improvement when compared to 29.0% obtained in subjects with partial adhesion to the protocol). TEWL values changed from 21.3 +/ 9.6 to 18.6 +/- 7.2 g/m2/h (P = 0.001) on the hands and from 16.6 +/- 9.0 to 10.5 +/- 4.6 g/m2/h (P = 0.001) on the forearm, confirming the skin barrier improvement. CONCLUSIONS: Our secondary prevention intervention was effective, leading to a reduction in clinical signs of dermatitis. TEWL measurement is a useful tool to evaluate skin integrity, mostly in apparently healthy skin, which may have a compromised barrier function, resulting in an exacerbation of the dermatitis. PMID- 27558201 TI - Fingolimod (FTY720) Reduces Cortical Infarction and Neurological Deficits During Ischemic Stroke Through Potential Maintenance of Microvascular Patency. AB - Fingolimod (FTY720) reduces infarct volume and improves neurological deficits in different rodent stroke models by modulating inflammatory and immune processes. However, studies on FTY720 regarding its non-immunological efficacy on ischemic cerebral tissue are sparse. Here we investigated whether FTY720 has cytoprotective and restorative properties following ischemic stroke in mice. Male mice received FTY720 (1mg/kg) or a vehicle solution intraperitoneally immediately prior to transient middle cerebral artery occlusion (tMCAO; 30 min.) and 48 hours thereafter. Infarct volume was determined on T2-weighted magnetic resonance images on day 1 and 7 after tMCAO. Motor function was assessed by the ladder rung walking test using a foot fault score. Specific immunostainings were performed to quantify neuronal density, astrocytic reactivity, microvascular density and expression of synaptophysin in the cortical perilesional area on consecutive brain slices. The amount of brain-derived neurotrophic factor (BDNF) was examined using ELISA analyses. FTY720 treatment significantly reduced infarct volumes and motor deficits compared to controls. Neuronal survival, astrogliosis as well as synaptogenesis and BDNF expression in the penumbra of the infarcted cortex did not significantly differ between the treatment groups. Taken together, our data support the hypothesis that the key mode of FTY720 action in stroke is the reduction of microvascular thrombosis and not a direct effect at the neurovascular unit (NVU). PMID- 27558203 TI - Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation. AB - Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C-C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility. PMID- 27558204 TI - Involvement of the Rcs regulon in the persistence of Salmonella Typhimurium in tomatoes. AB - It is becoming clear that human enteric pathogens, like Salmonella, can efficiently colonize vegetative and reproductive organs of plants. Even though the bacterium's ability to proliferate within plant tissues has been linked to outbreaks of salmonellosis, little is known about regulatory and physiological adaptations of Salmonella, or other human pathogens, to their persistence in plants. A screen of Salmonella deletion mutants in tomatoes identified rcsA and rcsB genes as those under positive selection. In tomato fruits, populations of Salmonella rcsB mutants were as much as 100-fold lower than those of the wild type. In the follow-up experiments, competitive fitness of rcsA and rcsB mutants was strongly reduced in tomatoes. Bioinformatics predictions identified a putative Salmonella RcsAB binding box (TTMGGAWWAABCTYA) and revealed an extensive putative RcsAB regulon, of which many members were differentially fit within tomatoes. PMID- 27558202 TI - Metal-responsive promoter DNA compaction by the ferric uptake regulator. AB - Short-range DNA looping has been proposed to affect promoter activity in many bacterial species and operator configurations, but only few examples have been experimentally investigated in molecular detail. Here we present evidence for a metal-responsive DNA condensation mechanism controlled by the Helicobacter pylori ferric uptake regulator (Fur), an orthologue of the widespread Fur family of prokaryotic metal-dependent regulators. H. pylori Fur represses the transcription of the essential arsRS acid acclimation operon through iron-responsive oligomerization and DNA compaction, encasing the arsR transcriptional start site in a repressive macromolecular complex. A second metal-dependent regulator NikR functions as nickel-dependent anti-repressor at this promoter, antagonizing the binding of Fur to the operator elements responsible for the DNA condensation. The results allow unifying H. pylori metal ion homeostasis and acid acclimation in a mechanistically coherent model, and demonstrate, for the first time, the existence of a selective metal-responsive DNA compaction mechanism controlling bacterial transcriptional regulation. PMID- 27558205 TI - Immediate termination of electrical status epilepticus in sleep after hemispherotomy is associated with significant progress in language development. AB - AIM: To study the effect of hemispherotomy on electrical status epilepticus in sleep (ESES) and language development. METHOD: Children with a confirmed diagnosis of ESES prior to surgery and a minimum of 24 months of developmental follow-up data were compared with age-matched controls without ESES. Language quotients (LQs) were calculated before and after surgery. RESULTS: Eleven patients (five females, six males) and 21 controls (11 females, 10 males) were included. Before surgery a significantly higher number of children in the study group (n=9) demonstrated severe developmental delay compared with children in the control group (n=13; p=0.015). In the study group ESES remitted immediately after surgery in 10 children, and a significant catch-up in LQs was observed in this group (preoperative mean 40.0 [standard deviation (SD) 22.2, interquartile range (IQR) 30.0-62.0]; postoperative mean 73.0 [SD 33.5, IQR 41.0-97.0]; p=0.037). There was no significant difference compared with controls at last follow-up after surgery (study group: five with severe impairment; control group: eight with severe impairment [p=0.971]). Overall, a favourable developmental outcome was associated with freedom from seizures (seizure-free group: median preoperative LQ 61.5, median postoperative LQ 78.0 [p=0.017]; seizure group: median preoperative LQ 35.5, median postoperative LQ 56.5 [p=0.273]) and antiepileptic drug withdrawal (off medication: median preoperative LQ 49.5, median postoperative LQ 78.0 [p=0.011]; on medication: median preoperative LQ 78.0, median postoperative LQ 83.5 [p=0.889]). INTERPRETATION: Children with ESES showed significantly lower preoperative language abilities than children without ESES. In cases with remission of ESES after surgery, marked improvement in LQs was noticed. This improvement cannot be fully explained by seizure-freedom alone as seizure-free children without preoperative ESES showed less improvement. PMID- 27558206 TI - Modest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States. PMID- 27558208 TI - Corrigendum: Electron pair escape from fullerene cage via collective modes. PMID- 27558207 TI - Examining binge-eating disorder and food addiction in adults with overweight and obesity. AB - OBJECTIVE: To compare four subgroups of adults with overweight/obesity: those with binge-eating disorder (BED) only, food addiction (FA) only, both BED + FA, and neither. METHODS: For this study, 502 individuals with overweight/obesity (body mass index >25 kg/m(2) ) completed a Web-based survey with established measures of eating and health-related behaviors. Most were female (n = 415; 83.2%) and White (n = 404; 80.8%); mean age and body mass index were 38.0 (SD = 13.1) years and 33.6 (SD = 6.9) kg/m(2) , respectively. RESULTS: Among 502 participants with overweight/obesity, 43 (8.5%) met BED criteria, 84 (16.6%) met FA criteria, 51 (10.1%) met both BED + FA criteria, and 328 (64.8%) met neither (control). The three groups with eating pathology (BED, FA, and BED + FA) had significantly greater disturbances on most measures (eating disorder psychopathology, impulsivity, and self-control) than the control group, while the FA and BED + FA groups reported significantly higher depression scores relative to the control group. The three eating groups did not differ significantly from each other. CONCLUSIONS: In this online survey, of those with overweight/obesity, nearly one third met criteria for BED, FA, or BED + FA, and these forms of disordered eating were associated with greater pathology relative to individuals with overweight/obesity without BED and FA. Future research should examine whether the presence of BED, FA, or co-occurring BED + FA requires tailored interventions in individuals with overweight or obesity. PMID- 27558209 TI - Genome-wide methylation profile following prenatal and postnatal dietary omega-3 fatty acid supplementation in pigs. AB - The objective of this study was to determine how prenatal and postnatal dietary omega-3 fatty acids alter white blood cell (leukocyte) DNA methylation of offspring. Fifteen gilts (n = 5 per treatment) were selected from one of three treatments: (i) control diet throughout gestation, lactation and nursery phase (CON); (ii) algal omega-3 fatty acid supplementation enriched in EPA and DHA (GromegaTM ) fed throughout gestation, lactation and nursery phase (Cn3); or (iii) GromegaTM supplementation maternally, during gestation and lactation only, and control diet during the nursery phase (Mn3). At 11 weeks of age and after 8 weeks of post-weaning nursery feeding, buffy coat genomic DNA was subjected to methyl CpG binding protein sequencing. The methylation enriched profile mapped to 26% of the porcine genome. On chromosome 4, a 27.7-kb differentially methylated region downstream of RUNX1T1 was hypomethylated in the Mn3 and Cn3 groups by 91.6% and 85.0% respectively compared to CON pigs. Conversely, hypermethylation was detected in intergenic regions of chromosomes 4 and 12. Regulatory impact factor and differential hubbing methods were used to identify pathways that were coordinately regulated by methylation due to feeding EPA and DHA during pregnancy. Despite limited ability to detect differential methylation, we describe methods that allow the identification of coordinated epigenetic regulation that could not otherwise be detected from subtle single locus changes in methylation. These data provide evidence of novel epigenetic regulation by maternal and early life supplementation of omega-3 fatty acids that may have implications to growth and inflammatory processes. PMID- 27558210 TI - Influence of low and normal appendicular lean mass on central blood pressure and wave reflection responses to muscle metaboreflex activation in postmenopausal women. AB - Sarcopenia, defined by reduced appendicular skeletal muscle mass (ASM)/height2 (ASMI), is associated with increased arterial stiffness (brachial-ankle pulse wave velocity, baPWV) and wave reflection (augmentation index, AIx). Blood pressure (BP) responses to metaboreflex activation (post-exercise muscle ischemia, PEMI) are exaggerated in older prehypertensives and hypertensives. We examined peripheral and aortic haemodynamics at rest and during PEMI in postmenopausal women with low-ASMI and normal-ASMI. Resting radial AIx and baPWV as well as brachial and aortic systolic BP, pulse pressure, systolic time index, and subendocardial viability ratio (SEVR) responses to PEMI were greater in women with low-ASMI than normal-ASMI. Increased baPWV associated with low-ASMI may play a major role in the exaggerated pulse pressure and SEVR responses to PEMI in postmenopausal women. PMID- 27558211 TI - Accuracy of a new diagnostic tool in deep infiltrating endometriosis: Positron emission tomography-computed tomography with 16alpha-[18F]fluoro-17beta estradiol. AB - AIM: Preoperative workup of deep infiltrating endometriosis is limited in the evaluation of extragenital and extrapelvic disease and in distinguishing between the previous surgical scar and active lesion. Histological verification remains the gold standard for diagnosis. The aim of this study was therefore to evaluate positron emission tomography-computed tomography (PET/CT) with an experimental estrogen receptor tracer (16alpha-[18F]fluoro-17beta-estradiol; [18F]FES) for accurate staging and non-invasive diagnosis of the disease. The primary endpoint was the feasibility of this tool on comparison with histology. The secondary endpoint was the accuracy of PET/CT in comparison with magnetic resonance imaging (MRI). METHODS: Four eligible subjects with extragenital endometriosis underwent MRI, PET/CT with [18F]FES, and laparoscopic excision of endometriosis in the same month. Region-by-region analysis was used to compare the findings of the two diagnostic tools with surgical histological specimens obtained during laparoscopy. RESULTS: A total of 40 anatomical regions were examined: seven were [18F]FES positive, four were positive on MRI and eight positive on histology. A total of nine regions were discordant. PET/CT agreed with histology in 9/9 of the discrepant findings. CONCLUSION: PET/CT with [18F]FES was feasible and had greater accuracy than MRI, particularly in patients with previous surgery. Further studies are needed, however, to investigate its role in bowel endometriosis in sites other than recto-sigmoid junction, nerve localization, and subcentimetric disease. PMID- 27558212 TI - Reproducibility in Chemical Research. AB - "... To what extent is reproducibility a significant issue in chemical research? How can problems involving irreproducibility be minimized? ... Researchers should be aware of the dangers of unconscious investigator bias, all papers should provide adequate experimental detail, and Reviewers have a responsibility to carefully examine papers for adequacy of experimental detail and support for the conclusions ..." Read more in the Editorial by Robert G. Bergman and Rick L. Danheiser. PMID- 27558213 TI - Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis. AB - BACKGROUND: The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end-stage retinitis pigmentosa. METHODS: The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30-patient single-arm clinical study. VisQoL is a multi attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub-group between baseline and the combined follow-up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow-up periods. RESULTS: Overall, 80 per cent of the patients reported difficulty in one or more dimensions pre-implant. Composite VisQoL utility scores at follow-up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. CONCLUSION: Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36-month follow-up, suggesting a long term, durable improvement. PMID- 27558214 TI - Commentary: Phage Therapy of Staphylococcal Chronic Osteomyelitis in Experimental Animal Model. PMID- 27558216 TI - Signs and symptoms associated with synthetic cannabinoid toxicity: systematic review. AB - AIMS: Use of synthetic cannabinoids is associated with significant physical and psychological harms. This research quantified reported toxicities from published reports and assessed the influence of size of the reported study population on rates of symptom reporting. METHODS: Systematic review of published case reports and case series of toxicity associated with use of synthetic cannabinoids. RESULTS: Symptoms associated with synthetic cannabinoid toxicity were reported for 3695 individuals, predominantly young males. Symptoms included physiological (e.g. tachycardia, hypertension, nausea/vomiting), emotional (e.g. agitation, irritability, paranoia), behavioural (e.g. drowsiness, aggression) and perceptual (e.g. hallucinations) domains. Most common symptoms were tachycardia (30.2% of cases), agitation (13.5%), drowsiness (12.3%), nausea/vomiting (8.2%) and hallucinations (7.6%). Death or serious medical complications were uncommon (e.g. death 0.2%, stroke 0.1%, myocardial infarction 0.09%). Case reports/smaller case series (n<10) reported statistically significantly higher rates for 29/34 symptoms than larger case series (n>=10), which could represent selection bias. CONCLUSIONS: Symptoms of synthetic cannabinoid toxicity are variable and cover a number of physical and psychological domains. Symptom reporting varies by study population size. Due to the variable presenting symptoms of synthetic cannabinoid toxicity, clinicians in emergency services should consider synthetic cannabinoid toxicity when evaluating young adult male patients presenting with unexplained agitation or cardiovascular symptoms. PMID- 27558215 TI - A Radially Organized Multipatterned Device as a Diagnostic Tool for the Screening of Topographies in Tissue Engineering Biomaterials. AB - Micro- and nanotextured biomaterial surfaces have been widely studied for their capacity to drive the regeneration of organized tissues. Nanotopographical features in the shape of groove-ridge patterns aim at mimicking the extracellular matrix organization. However, to date, a wide array of groove and ridge sizes has been described. In this work, we therefore tested a device composed of a multipatterned array consisting of six patterns of radially arranged parallel nanogrooves, with a pitch ranging from 0 to 1000 nm and a depth ranging from 0 to 170 nm, to be used as a tool for the expeditious and simultaneous screening of surface topographies aiming the regeneration of anisotropically organized tissues such as ligament. The topographies were reproduced in (1) epoxy resin or (2) membranes produced by the crosslinking of platelet lysate (PL) with genipin (gPL). Both materials were seeded with periodontal ligament cells (PDLCs) and the proliferation, migration, as well as cell alignment were assessed. The effect of topography in PDLCs was only evident in terms of cell organization, resulting in a highly anisotropic organization of the cells for the 1000 and 600 nm patterns, and in an increased isotropic organization for shallower topographies. Overall, our results suggest that this multipatterned system can be a valuable diagnostic tool for biomaterials aiming at the regeneration of anisotropically organized tissues, such as periodontal ligament. PMID- 27558217 TI - Severe motor and vocal tics controlled with Sativex(r). AB - OBJECTIVES: A single case report on cannabinoid treatment for treatment-resistant Tourette syndrome (TS). METHOD: Our subject received 10.8 mg Tetrahydocannabinol and 10 mg cannabidiol daily, in the form of two oro-mucosal sprays of 'Sativex(r)', twice daily. Assessment was pre-treatment and at week one, two, and four during treatment. He completed the Yale Global Tic Severity Scale as a subjective measure, and was videoed at each stage. The videos were objectively rated by two assessors, blind to the stage of treatment, using the Original Rush Videotape Rating Scale. RESULTS: Both subjective and objective measures demonstrated marked improvement in the frequency and severity of motor and vocal tics post-treatment. There was good interrater reliability of results. CONCLUSIONS: Our results support previous research suggesting that cannabinoids are a safe and effective treatment for TS and should be considered in treatment resistant cases. Further studies are needed to substantiate our findings. PMID- 27558218 TI - Same-sex marriage and mental health. AB - OBJECTIVES: It has been proposed that legislation for same-sex marriage has a positive mental health benefit. The purpose of this paper is to review and evaluate the empirical and conceptual links between same-sex marriage and mental health. CONCLUSIONS: There are substantive methodological issues in the four surveys and comparisons undertaken. Difficulties with the validity of the evidence are discussed. Conceptual difficulties in the arguments relating to victimisation as well as the psychology of marriage are highlighted. It was concluded that it is premature to make claims of causality vis-a-vis same-sex marriage legislation and mental health. PMID- 27558219 TI - The impact on clinical practice of the 2015 reforms to the New South Wales Mental Health Act. AB - OBJECTIVES: The Mental Health Act 2007 (NSW) ( MHA) was recently reformed in light of the recovery movement and the United Nations Convention on the Rights of Persons with Disabilities. We analyse the changes and describe the impact that these reforms should have upon clinical practice. CONCLUSIONS: The principles of care and treatment added to the MHA place a strong onus on clinicians to monitor patients' decision-making capacity, institute a supported decision-making model and obtain consent to any treatment proposed. Patients competently refusing treatment should only be subject to involuntary treatment in extraordinary circumstances. Even when patients incompetently refuse treatment, clinicians must make every effort reasonably practicable to tailor management plans to take account of any views and preferences expressed by them or made known via friends, family or advance statements. PMID- 27558220 TI - Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis. AB - Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturation along CVA in neonates. Eight 21-day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially along CVA, and proteomics was used to analyze the changes in proteins expression in epithelial cells along CVA. The identified differentially expressed proteins were mainly involved in cellular process, metabolic process, biological regulation, pigmentation, multicellular organizational process and so on. The energy metabolism in intestinal epithelial cells of piglets was increased from the bottom of crypt to the top of villi. Moreover, the expression of proteins related to the metabolism of glucose, most of amino acids, and fatty acids was increased in intestinal epithelial cells during maturation along CVA, while the expression of proteins related to glutamine metabolism was decreased from crypt to villus tip. The expression of proteins involved in citrate cycle was also increased intestinal epithelial cells during maturation along CVA. Moreover, dietary supplementation with different energy sources had different effects on intestinal structure of weaned piglets. PMID- 27558221 TI - Temporal trends in childhood mortality in Ghana: impacts and challenges of health policies and programs. AB - BACKGROUND: Following the adoption of the Millennium Development Goal 4 (MDG 4) in Ghana to reduce under-five mortality by two-thirds between 1990 and 2015, efforts were made towards its attainment. However, impacts and challenges of implemented intervention programs have not been examined to inform implementation of Sustainable Development Goal 3.2 (SDG 3.2) that seeks to end preventable deaths of newborns and children aged under-five. Thus, this study aimed to compare trends in neonatal, infant, and under-five mortality over two decades and to highlight the impacts and challenges of health policies and intervention programs implemented. DESIGN: Ghana Demographic and Health Survey data (1988 2008) were analyzed using trend analysis. Poisson regression analysis was applied to quantify the incidence rate ratio of the trends. Implemented health policies and intervention programs to reduce childhood mortality in Ghana were reviewed to identify their impact and challenges. RESULTS: Since 1988, the annual average rate of decline in neonatal, infant, and under-five mortality in Ghana was 0.6, 1.0, and 1.2%, respectively. From 1988 to 1989, neonatal, infant, and under-five mortality declined from 48 to 33 per 1,000, 72 to 58 per 1,000, and 108 to 83 per 1,000, respectively, whereas from 1989 to 2008, neonatal mortality increased by 2 per 1,000 while infant and under-five mortality further declined by 6 per 1,000 and 17 per 1,000, respectively. However, the observed declines were not statistically significant except for under-five mortality; thus, the proportion of infant and under-five mortality attributed to neonatal death has increased. Most intervention programs implemented to address childhood mortality seem not to have been implemented comprehensively. CONCLUSION: Progress towards attaining MDG 4 in Ghana was below the targeted rate, particularly for neonatal mortality as most health policies and programs targeted infant and under-five mortality. Implementing neonatal-specific interventions and improving existing programs will be essential to attain SDG 3.2 in Ghana and beyond. PMID- 27558222 TI - Sea lampreys elicit strong transcriptomic responses in the lake trout liver during parasitism. AB - BACKGROUND: The sea lamprey (Petromyzon marinus) is a jawless vertebrate that parasitizes fish as an adult and, with overfishing, was responsible for the decline in lake trout (Salvelinus namaycush) populations in the Great Lakes. While laboratory studies have looked at the rates of wounding on various fish hosts, there have been few investigations on the physiological effects of lamprey wounding on the host. In the current study, two morphotypes of lake trout, leans and siscowets, were parasitized in the laboratory by sea lampreys and the liver transcriptomes of parasitized and nonparasitized fish were analyzed by RNA-seq (DESeq2 and edgeR) to determine which genes and gene pathways (Ingenuity Pathway Analysis) were altered by lamprey parasitism. RESULTS: Overall, genes encoding molecules involved in catalytic (e.g., enzymatic) and binding activities (factors and regulators) predominated the regulated gene lists. In siscowets, the top upregulated gene was growth arrest and DNA-damage-inducible protein and for leans it was interleukin-18-binding protein. In leans, the most significantly downregulated gene was UDP-glucuronosyltransferase 2A2 - DESeq2 or phosphotriesterase related - edgeR. For siscowets, the top downregulated gene was C-C motif chemokine 19 - DESeq2 or GTP-binding protein Rhes - edgeR. Gene pathways associated with inflammatory-related responses or factors (cytokines, chemokines, oxidative stress, apoptosis) were regulated following parasitism in both morphotypes. However, pathways related to energy metabolism (glycolysis, gluconeogenesis, lipolysis, lipogenesis) were also regulated. These pathways or the intensity or direction (up/downregulation) of regulation were different between leans and siscowets. Finally, one of the most significantly downregulated pathways in both leans and siscowets was the kynurenine (tryptophan degradation) pathway. CONCLUSIONS: The results indicate a strong transcriptional response in the lake trout to lamprey parasitism that entails genes involved in the regulation of inflammation and cellular damage. Responses to energy utilization as well as hydromineral balance also occurred indicating an adjustment in the host to energy demands and osmotic imbalances during parasitism. Given the role of the kynurenine pathway in promoting immunotolerance in mammals, the downregulation observed in this pathway during parasitism may signify an attempt by the host to inhibit any feedback suppression of the immune response to the lamprey. PMID- 27558223 TI - An Investigation of the Innate Immune Response in Bovine Mammary Epithelial Cells Challenged by Prototheca zopfii. AB - Prototheca zopfii is an important bovine mastitis pathogen, which could result in severe mammary infection. However, the innate immune response in bovine mastitis associated with P. zopfii was not clear. Therefore, the aim of this study is to investigate in vitro innate immune responses implicated by P. zopfii. Bovine mammary epithelial cells (bMECs) were infected with 5.0 * 104 cells/ml P. zopfii genotypes I and II independently, and the mRNA expression of TLR-2, TLR-4, TNF alpha, IL-1beta, IL-8, NOD-1, NOD-2 and beta-defensin-5 was determined by real time polymerase chain reaction (RT-PCR) over a time course of 1, 3, 6, 12 and 24 h. The detection of the NF-kappaB p65 protein in nucleus and cytoplasm of infected bMECs over the same time course was evaluated. Results showed that P. zopfii genotype II has ability to up-regulate the expression of TLR-2, TLR-4, TNF alpha, IL-1beta, IL-8, NOD-1, NOD-2 and beta-defensin-5 'more strongly than genotype I. Western blot results showed that when bMECs were challenged by P. zopfii genotype II, the expression of NF-kappaB p65 protein in the nucleus was up regulated, while in cytoplasm it appeared to be repressed, which indicated that bMECs partly regulate the innate immune responses and inflammation by the NF kappaB signaling pathway while being infected by P. zopfii genotype II. It was concluded that adhesion of genotype II was stronger than genotype I, and therefore the genotype II regulatory ability is more robust than that of the genotype I, which causes inflammation of bovine mammary tissue. PMID- 27558225 TI - An Analytical Method to Measure Free-Water Tritium in Foods using Azeotropic Distillation. AB - A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant has raised concerns about the discharge of contaminated water containing tritium ((3)H) from the nuclear power plant into the environment and into foods. In this study, we explored convenient analytical methods to measure free-water (3)H in foods using a liquid scintillation counting and azeotropic distillation method. The detection limit was 10 Bq/L, corresponding to about 0.01% of 1 mSv/year. The (3)H recoveries were 85-90% in fruits, vegetables, meats and fishes, 75-85% in rice and cereal crops, and less than 50% in sweets containing little water. We found that, in the case of sweets, adding water to the sample before the azeotropic distillation increased the recovery and precision. Then, the recoveries reached more than 75% and RSD was less than 10% in all food categories (13 kinds). Considering its sensitivity, precision and simplicity, this method is practical and useful for (3)H analysis in various foods, and should be suitable for the safety assessment of foods. In addition, we examined the level of (3)H in foods on the Japanese market. No (3)H radioactivity was detected in any of 42 analyzed foods. PMID- 27558224 TI - In Vitro Susceptibility of Sporothrix brasiliensis to Essential Oils of Lamiaceae Family. AB - This study evaluated the chemical, cytotoxic and anti-Sporothrix brasiliensis properties of commercial essential oils of rosemary (Rosmarinus officinalis L.), oregano (Origanum vulgare L.) and marjoram (Origanum majorana L.). Chemical composition of the oils was identified through gas chromatography with flame ionization detector, and cytotoxicity was performed through MTT assay in VERO cell line. Anti-S. brasiliensis activity was performed according to the CLSI M38 A2 guidelines using isolates obtained from cats and dogs. The major compounds found were carvacrol in the oregano oil (73.9 %) and 1,8-cineole in rosemary and marjoram oils (49.4 and 20.9 %, respectively). All S. brasiliensis isolates were susceptible to the plant oils, including itraconazole-resistant ones. Marjoram and rosemary oils showed MIC90 of 0.56 and 1.12 mg ml-1, and MFC90 of 4.5 and 9 mg ml-1, respectively. For oregano oil, a strong antifungal activity was observed with MIC90 and MFC90 values <=0.07 mg ml-1. The weakest cytotoxicity was observed for rosemary oil. Further studies should be undertaken to evaluate the safety and efficacy of these essential oils in sporotrichosis. PMID- 27558226 TI - Determination of Fluopicolide in Livestock Products and Seafood by LC-MS/MS. AB - An analytical method for the determination of fluopicolide in livestock products and seafood was developed using LC-MS/MS. Sodium chloride was added to livestock products and seafood samples and fluopicolide was extracted twice with acetone after acidification with formic acid. The fat from the crude extract was removed using a macroporous diatomaceous earth column, followed by purification with a combination of mini-columns of GC (graphite carbon) and PSA (ethylenediamine-N propyl silylation silica gel). The average recovery (n=5) of fluopicolide from 10 types of livestock products and seafood (cattle fat, cattle liver, cattle muscle, chicken, eel, egg, freshwater clam, honey, milk and salmon) spiked at the MRLs or at the uniform limit (0.01 ppm) was 96-100%, with a relative standard deviation of 2.3-6.2%. The limit of quantitation of the developed method was calculated to be 0.01 mg/kg. PMID- 27558227 TI - Improvement of Nicotinic Acid and Nicotinamide Analysis in Meats and Meat Products by HPLC and LC-MS/MS with Solid-Phase Extraction. AB - A method for nicotinic acid (NA) and nicotinamide (NAA) analysis in meats was developed. NA and NAA were extracted from meats or meat products with metaphosphate aqueous solution. The extract was cleaned up with an Oasis MCX cartridge. The cartridge was washed with 2% acetic acid (v/v) and acetic acid methanol solution. NA and NAA were eluted with ammonia-methanol solution. NA and NAA in the eluate were chromatographed on a Scherzo SM-C18 (3.0*150 mm, 3.0 MUm) column with 20 mmol/L ammonium acetate containing 0.1% acetic acid-acetonitrile (97 : 3) as a mobile phase and were monitored at 261 nm. Quantification was performed by LC and LC-MS/MS. Calibration curves showed high linearity (correlation coefficient>0.998) between 1-25 MUg/mL for LC and LC-MS/MS. Recoveries were 84-108% (CV?5.8%) by HPLC and 79-105% (CV?9.0%) by LC-MS/MS. The limit of quantitation for NA was 0.005-0.01 g/kg and that for NAA was 0.01-0.02 g/kg. PMID- 27558228 TI - Simultaneous Determination of Seven Kinds of Fungicides in Citrus Fruits by Gas Chromatograghy/Mass Spectrometry. AB - A simple and accurate procedure was developed for the determination of seven fungicides, azoxystrobin (AZO), diphenyl (DP), fludioxonil (FLUDI), imazalil (IMZ), o-phenylphenol (OPP), pyrimethanil (PYRI) and thiabendazole (TBZ), in citrus fruits. The citrus fruit sample was extracted with acetonitrile and cleaned up with a graphite carbon/aminopropyl silanized silica gel solid-phase extraction cartridge using acetonitrile-toluene (3 : 1, v/v) as the eluent. Triphenylene was used as an internal standard (I.S.) at the concentration of 0.5 MUg/mL. The sample solution was subjected to GC-MS utilizing the matrix-matched standard solution method. The recoveries of AZO, FLUDI, IMZ, OPP, PYRI and TBZ spiked in domestic citrus fruits (Satsuma mandarin) at the level of 0.01-10.0 MUg/g were 72.8-104% and the limits of quantification were 0.01 MUg/g. The recoveries of DP spiked in domestic citrus fruits at the level of 0.01-70.0 MUg/g were 70.8-80.4% and the limit of quantification was 0.01 MUg/g. The proposed method was applied to the determination of fungicides in citrus fruits purchased in various markets. PMID- 27558229 TI - Validation Study on a Rapid Method for Simultaneous Determination of Pesticide Residues in Vegetables and Fruits by LC-MS/MS. AB - A validation study was carried out on a rapid method for the simultaneous determination of pesticide residues in vegetables and fruits by LC-MS/MS. Preparation of the test solution was performed by a solid-phase extraction technique with QuEChERS (STQ method). Pesticide residues were extracted with acetonitrile using a homogenizer, followed by salting-out and dehydration at the same time. The acetonitrile layer was purified with C18 and PSA mini-columns. The method was assessed for 130 pesticide residues in 14 kinds of vegetables and fruits at the concentration level of 0.01 MUg/g according to the method validation guideline of the Ministry of Health, Labour and Welfare of Japan. As a result 75 to 120 pesticide residues were determined satisfactorily in the tested samples. Thus, this method could be useful for a rapid and simultaneous determination of multi-class pesticide residues in various vegetables and fruits. PMID- 27558230 TI - Attentional artifacts in sensorimotor coupling in the postural control of young adults. AB - Although postural control requires the integration of different sensory cues, little is known about the role of attentional artifacts on the individual's ability to properly respond to postural challenges. This study investigated the effects of concomitant tasks (cognitive and postural) on the relationship between visual information and body sway. Thirty healthy adults were asked to stand still inside of a moving room on normal and reduced bases of support. Initially, the participants were not aware of any visual manipulation and were asked to perform tasks that required concomitant attentional demands. Then, all participants were informed about the visual manipulation and were requested to resist it. The results showed that information about visual manipulation changed the coupling between visual information and body sway, but only in a less demanding task, and that it was affected by the concomitant task. The coupling between visual information and body sway for postural control does not demand attention on a regular basis, but any change in this relationship demands attention and occurs in less demanding postural tasks. PMID- 27558231 TI - Real-time feedback of dynamic foot pressure index for gait training of toe walking children with spastic diplegia. AB - PURPOSE: The aim of this study was to determine whether and how real-time feedback of dynamic foot pressure index (DFPI) could be used to correct toe walking gait in spastic diplegic children with dynamic equinus. METHODS: Thirteen spastic diplegic children with dynamic equinus were asked to wear a monitoring device to record their ambulation during daily gait, conventional training gait, and feedback training gait. Parameters based on their DFPI and stride duration were compared among the three test conditions. RESULTS: The results with feedback training were significantly better for all DFPI parameters in comparison to patients' daily gait and showed significant improvements in DFPI for toe-walking gait and percentage of normal gait in comparison to conventional training methods. Moreover, stride duration under two training gaits was longer than patient's daily gait, but there was no significant difference between the two training gaits. CONCLUSIONS: Although the stride duration for the two training gaits was similar, gait training with real-time feedback of DFPI did produce noticeably superior results by increasing heel-loading impulse of toe-walking gait and percentage of normal gait in comparison to convention training methods. However, its effectiveness was still impacted by the motion limitations of diplegic children. Implications for Rehabilitation The DFPI-based gait training feedback system introduced in this study was shown to be more effective at toe walking gait rehabilitation training over conventional training methods. The feedback system accomplished superior improvement in correcting toe-walking gait, but its effectiveness in an increasing heel-loading impulse in normal gait was still limited by the motion limitations of diplegic children. Stride duration of normal gait and toe-walking gait was similar under conventional and feedback gait training. PMID- 27558232 TI - Pharmacokinetics of Venetoclax, a Novel BCL-2 Inhibitor, in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma. AB - Venetoclax is a selective BCL-2 inhibitor that is approved in the United States for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. The aim of this analysis was to characterize venetoclax pharmacokinetics in the plasma and urine of patients with hematological malignancies and evaluate the effect of dose proportionality, accumulation, weak and moderate CYP3A inhibitors, as well as low- and high-fat meals on venetoclax pharmacokinetics. Patients received a once-daily venetoclax dose of 20 to 1200 mg. Pharmacokinetic parameters were estimated using noncompartmental methods. Venetoclax peak exposures were achieved at 5 to 8 hours under low-fat conditions, and the mean terminal-phase elimination half-life ranged between 14.1 and 18.2 hours at different doses. Venetoclax steady-state exposures showed minimal accumulation and increased proportionally over the dose range of 300 to 900 mg. Low-fat and high-fat meals increased venetoclax exposures by approximately 4-fold relative to the fasting state. Moderate CYP3A inhibitors increased venetoclax exposures by 40% to 60%, whereas weak CYP3A inhibitors had no effect. A negligible amount of venetoclax was excreted in the urine. In summary, venetoclax exhibits a pharmacokinetic profile that is compatible with once-daily dosing with food regardless of fat content. Concomitant use of venetoclax with moderate CYP3A inhibitors should be avoided or venetoclax dose should be reduced during the venetoclax initiation and ramp-up phase in CLL patients. Renal excretion plays a minimal role in the elimination of venetoclax. PMID- 27558233 TI - Unfractionated heparin or low-molecular-weight heparin in the elderly. AB - With the ageing of the general population, clinicians are facing with increased frequency the challenge of administering parenteral anti-coagulation therapy in the elderly, the main indications being venous thromboembolism (VTE), acute coronary syndromes (ACS), atrial fibrillation and bridging therapy. Assessing the risk/benefit ratio is always difficult in this category of patients, because of the higher risk for hemorrhagic events, although in most cases the benefit outweighs the risk, especially in the setting of VTE. The development of early invasive strategies for treating ACS has improved outcomes, while reducing the need for prolonged anticoagulation. For ST-segment elevation acute myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) is the mainstay treatment with well documented benefits in terms of mortality reduction regardless of the patient's age. However, evidence is less strong regarding early invasive treatment for over 75-year old Non-STEMI patients, resulting in a significant percentage being treated conservatively, including parenteral anticoagulation. This review will focus on the use of parenteral anticoagulation (unfractionated or low-molecular weight heparin) in older patients. We will analyze current guidelines-based parenteral anticoagulation indications, while focusing on specific considerations in the elderly, such as: frailty and comorbidities, pharmacokinetics, the hemorrhagic risk and available clinical evidence. The goal is to offer a comprehensive tool for the clinician managing parenteral anticoagulation in older patients. PMID- 27558234 TI - Nox4 contributes to the hypoxia-mediated regulation of actin cytoskeleton in cerebrovascular smooth muscle. AB - Ischemia/reperfusion and the resulting oxidative/nitrative stress impair cerebral myogenic tone via actin depolymerization. While it is known that NADPH oxidase (Nox) family is a major source of vascular oxidative stress; the extent and mechanisms by which Nox activation contributes to actin depolymerization, and equally important, the relative role of Nox isoforms in this response is not clear. AIM: To determine the role of Nox4 in hypoxia-mediated actin depolymerization and myogenic-tone impairment in cerebral vascular smooth muscle. MAIN METHODS: Control and Nox4 deficient (siRNA knock-down) human brain vascular smooth muscle cells (HBVSMC) were exposed to 30-min hypoxia/45-min reoxygenation. Nox2, Nox4, inducible and neuronal nitric oxide synthase (iNOS and nNOS) and nitrotyrosine levels as well as F:G actin were determined. Myogenic-tone was measured using pressurized arteriography in middle cerebral artery isolated from rats subjected to sham, 30-min ischemia/45-min reperfusion or ex-vivo oxygen glucose deprivation in the presence and absence of Nox inhibitors. RESULTS: Nox4 and iNOS expression were significantly upregulated following hypoxia or ischemia/reperfusion. Hypoxia augmented nitrotyrosine levels while reducing F actin. These effects were nullified by inhibiting nitration with epicatechin or pharmacological or molecular inhibition of Nox4. Ischemia/reperfusion impaired myogenic-tone, which was restored by the selective inhibition of Nox4. CONCLUSION: Nox4 activation in VSMCs contributes to actin depolymerization after hypoxia, which could be the underlying mechanism for myogenic-tone impairment following ischemia/reperfusion. PMID- 27558235 TI - Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer's Disease Treated with Hippocampal Neural Stem Cells. AB - Transplantation with neural stem cells (NSCs) is a promising clinical therapy for Alzheimer's disease (AD). However, the final fate of grafted NSCs is mainly determined by the host microenvironment. Therefore, this study investigated the role of Sanjiao acupuncture in the NSCs-treated hippocampus of a mouse model, senescence-accelerated mouse prone 8 (SAMP8) using Western blot, real-time fluorescent PCR, and immunofluorescence techniques. Meanwhile, we developed a co culture model of hippocampal tissue specimens and NSCs in vitro, to observe the effects of acupuncture on survival, proliferation and differentiation of grafted NSCs using flow cytometry. Results showed that acupuncture pre- and post-NSCs transplantation significantly improved senescence-induced cognitive dysfunction (P < 0.05); upregulated the expression of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and brain-derived neurotrophic factor (BDNF) (P < 0.05); and also increased the count of neuron-specific nuclear protein (NeuN)- and glial fibrillary acidic protein (GFAP)-positive cells (P < 0.05). Therapeutic acupuncture may regulate the cytokine levels associated with survival, proliferation, and differentiation of NSCs in hippocampal microenvironment, to promote the repair of damaged cells, resulting in improved cognitive performance in mice. PMID- 27558236 TI - Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression. AB - Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis. PMID- 27558237 TI - Adenine Nucleotides Control Proliferation In Vivo of Rat Retinal Progenitors by P2Y1 Receptor. AB - Previous studies demonstrated that exogenous ATP is able to regulate proliferation of retinal progenitor cells (RPCs) in vitro possibly via P2Y1 receptor, a G protein-coupled receptor. Here, we evaluated the function of adenine nucleotides in vivo during retinal development of newborn rats. Intravitreal injection of apyrase, an enzyme that hydrolyzes nucleotides, reduced cell proliferation in retinas at postnatal day 2 (P2). This decrease was reversed when retinas were treated together with ATPgamma-S or ADPbeta-S, two hydrolysis resistant analogs of ATP and ADP, respectively. During early postnatal days (P0 to P5), an increase in ectonucleotidase (E-NTPDase) activity was observed in the retina, suggesting a decrease in the availability of adenine nucleotides, coinciding with the end of proliferation. Interestingly, intravitreal injection of the E-NTPDase inhibitor ARL67156 increased proliferation by around 60 % at P5 rats. Furthermore, immunolabeling against P2Y1 receptor was observed overall in retina layers from P2 rats, including proliferating Ki-67-positive cells in the neuroblastic layer (NBL), suggesting that this receptor could be responsible for the action of adenine nucleotides upon proliferation of RPCs. Accordingly, intravitreal injection of MRS2179, a selective antagonist of P2Y1 receptors, reduced cell proliferation by approximately 20 % in P2 rats. Moreover, treatment with MRS 2179 caused an increase in p57KIP2 and cyclin D1 expression, a reduction in cyclin E and Rb phosphorylated expression and in BrdU-positive cell number. These data suggest that the adenine nucleotides modulate the proliferation of rat RPCs via activation of P2Y1 receptors regulating transition from G1 to S phase of the cell cycle. PMID- 27558239 TI - Accuracy of a modified axiolateral radiographic hip projection in suspected cases of hip fracture: experience and results from a regional trauma centre. AB - Conventional radiographs play an important role as a first line imaging modality in the assessment for suspected hip fractures in the majority of trauma centres. The routinely performed radiographic projections in our emergency department for patients with clinically suspected hip fractures include antero-posterior (AP) and cross-table lateral views of the affected hip. Certain clinical scenarios which include the presence of significant pain of the injured lower limb, a large patient habitus, as well as pre-existing patient morbidity which would limit the range of motion of the lower limbs, for example the presence of prior joint replacement surgery or lower limb contractures, may however preclude proper positioning of the patient to obtain an optimal cross-table lateral view of the affected hip. The objective of this study is to investigate whether a modified axiolateral hip projection would be a feasible alternative to the cross-table lateral projection in the initial radiographic assessment of suspected cases of hip fracture. PMID- 27558238 TI - Regulatory Role of Circular RNAs and Neurological Disorders. AB - Circular RNAs (circRNAs) are a class of long noncoding RNAs that are characterized by the presence of covalently linked ends and have been found in all life kingdoms. Exciting studies in regulatory roles of circRNAs are emerging. Here, we summarize classification, characteristics, biogenesis, and regulatory functions of circRNAs. CircRNAs are found to be preferentially expressed along neural genes and in neural tissues. We thus highlight the association of circRNA dysregulation with neurodegenerative diseases such as Alzheimer's disease. Investigation of regulatory role of circRNAs will shed novel light in gene expression mechanisms during development and under disease conditions and may identify circRNAs as new biomarkers for aging and neurodegenerative disorders. PMID- 27558240 TI - Promoting good policy for leadership and governance of health related rehabilitation: a realist synthesis. AB - BACKGROUND: Good governance may result in strengthened performance of a health system. Coherent policies are essential for good health system governance. The overall aim of this research is to provide the best available scientific evidence on principles of good policy related leadership and governance of health related rehabilitation services in less resourced settings. This research was also conducted to support development of the World Health Organization's (WHO) Guidelines on health related rehabilitation. METHODS: An innovative study design was used, comprising two methods: a systematic search and realist synthesis of literature, and a Delphi survey of expert stakeholders to refine and triangulate findings from the realist synthesis. In accordance with Pawson and Tilley's approach to realist synthesis, we identified context mechanism outcome pattern configurations (CMOCs) from the literature. Subsequently, these CMOCs were developed into statements for the Delphi survey, whereby 18 expert stakeholders refined these statements to achieve consensus on recommendations for policy related governance of health related rehabilitation. RESULTS: Several broad principles emerged throughout formulation of recommendations: participation of persons with disabilities in policy processes to improve programme responsiveness, efficiency, effectiveness, and sustainability, and to strengthen service-user self-determination and satisfaction; collection of disaggregated disability statistics to support political momentum, decision-making of policymakers, evaluation, accountability, and equitable allocation of resources; explicit promotion in policies of access to services for all subgroups of persons with disabilities and service-users to support equitable and accessible services; robust inter-sectoral coordination to cultivate coherent mandates across governmental departments regarding service provision; and 'institutionalizing' programmes by aligning them with preexisting Ministerial models of healthcare to support programme sustainability. CONCLUSIONS: Alongside national policymakers, our policy recommendations are relevant for several stakeholders, including service providers and service-users. This research aims to provide broad policy recommendations, rather than a strict formula, in acknowledgement of contextual diversity and complexity. Accordingly, our study proposes general principles regarding optimal policy related governance of health related rehabilitation in less resourced settings, which may be valuable across diverse health systems and contexts. PMID- 27558241 TI - Morphological and functional alteration of erythrocyte ghosts and giant unilamellar vesicles caused by Vipera latifi venom. AB - Snake bites are an endemic public health problem in Iran, both in rural and urban area. Viper venom as a hemolytic biochemical "cocktail" of toxins, primarily cause to the systemic alteration of blood cells. In the sixties and seventies, human erythrocytes were extensively studied, but the mechanical and chemical stresses commonly exerted on red blood cells continue to attract interest of scientists for the study of membrane structure and function. Here, we monitor the effect of Vipera latifi venom on human erythrocytes ghost membranes using phase contrast and fluorescent microscopy and changes in ATPase activity under snake venom influence in vitro. The ion pumps [Na+,K+]-ATPase and (Ca2++Mg2+)-ATPase plays a pivotal role in the active transport of certain cations and maintenance of intracellular electrolyte homeostasis. We also describe the interaction of Vipera latifi (VL) venom with giant unilamellar vesicles (GUVs) composed of the native phospholipid mixtures visualized by the membrane fluorescence probe, ANS, used to assess the state of membrane and specifically mark the phospholipid domains. PMID- 27558242 TI - Alterations of telomere length and mtDNA copy number are associated with overall survival in hepatocellular carcinoma patients treated with transarterial chemoembolization. AB - PURPOSE: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) copy number (mtDNAcn) and relative telomere length (RTL) may be implicated in the tumorigenesis of several malignancies. Alterations of both RTL and mtDNAcn are generally accepted as independent biomarkers for predicting risk and prognosis in various cancers. The aim of this study was to evaluate the prognostic value of combining leukocyte RTL with mtDNAcn (RTL-mtDNAcn) in hepatocellular carcinoma (HCC). METHODS: RTL and mtDNAcn in peripheral blood leukocytes (PBLs) were measured using a real-time PCR-based method in a total of 250 HCC patients treated with transcatheter arterial chemoembolization (TACE). We evaluated the associations between RTL and/or mtDNAcn and HCC overall survival using Kaplan-Meier curve analysis and Cox proportional hazards regression model. RESULTS: We found that patients with longer leukocyte RTL or lower mtDNAcn had shorter overall survival time. The univariate analysis (HR 1.63, 95 % CI 1.23 2.17, P = 7.7 * 10(-4)) and multivariate analysis (HR 1.78, 95 % CI 1.31-2.42, P = 2.4 * 10(-4)) indicated that longer leukocyte RTL was significantly associated with poorer OS in HCC patients. Kaplan-Meier curve analysis showed that patients with longer RTL had shorter overall survival time than those with shorter RTL (log-rank P = 0.001). Patients with lower mtDNA copy number was significantly associated with poorer OS by Cox proportional hazards model using both univariate (HR 1.60, 95 % CI 1.21-2.13, P = 0.001) and multivariate analyses (HR 1.77, 95 % CI 1.30-2.41, P = 2.8 * 10(-4)). Kaplan-Meier curve analysis showed that patients with lower mtDNA content had significantly shorter overall survival time than those with higher mtDNA content (log-rank P = 0.001). Furthermore, combination of leukocyte RTL and mtDNAcn significantly improved the efficacy of predicting HCC prognosis. Patients with longer RTL and lower mtDNAcn exhibited a significantly poorer overall survival in both the univariate analysis (HR 2.21, 95 % CI 1.52 3.22, P = 3.5 * 10(-5)) and multivariate analysis (HR 2.60, 95 % CI 1.73-3.90, P = 4.3 * 10(-6)). The effect on patient prognosis was more evident in patients with longer RTL and lower mtDNAcn than in those with shorter RTL and lower mtDNA (HR 2.11, 95 % CI 1.34-3.32, P = 0.001) or in those with longer RTL and higher mtDNA (HR 2.10, 95 % CI 1.34-3.27, P = 0.001). CONCLUSIONS: Our data suggest that combination of leukocyte RTL-mtDNAcn may be a potential efficient prognostic marker for HCC patients receiving the TACE treatment. PMID- 27558243 TI - Hip fractures in the elderly: The role of cortical bone. AB - INTRODUCTION: Osteoporosis is characterised by poor bone quality arising from alterations to trabecular bone. However, recent studies have also described an important role of alterations to cortical bone in the physiopathology of osteoporosis. Although dual-energy X-ray absorptiometry (DXA) is a valid method to assess bone mineral density (BMD), real bone fragility in the presence of comorbidities cannot be evaluated with this method. The aim of this study was to evaluate if cortical thickness could be a good parameter to detect bone fragility in patients with hip fracture, independent of BMD. METHODS: A retrospective study was conducted on 100 patients with hip fragility fractures. Cortical index was calculated on fractured femur (femoral cortical index [FCI]) and, when possible, on proximal humerus (humeral cortical index [HCI]). All patients underwent densitometric evaluation by DXA. RESULTS: Average value of FCI was 0.43 and of HCI was 0.25. Low values of FCI were found in 21 patients with normal or osteopenic values of BMD, while low values of HCI were found in three patients with non-osteoporotic values of BMD. DISCUSSION AND CONCLUSION: Cortical thinning measured from X-Ray of the femur identifies 21% additional fracture cases over that identified by a T-score <-2.5 (57%). FCI could be a useful tool to evaluate bone fragility and to predict fracture risk even in patients with normal and osteopenic BMD. PMID- 27558244 TI - Evolution of trauma care in Italy: What should we expect in the future? PMID- 27558245 TI - Culturally adapting a physical activity intervention for Somali women: the need for theory and innovation to promote equity. AB - There is pressing need for innovation in clinical research to more effectively recruit, engage, retain, and promote health among diverse populations overburdened by health disparities. The purpose of this study is to provide a detailed illustration of the cultural adaptation of an evidence-based intervention to bolster translational research with currently underserved communities. The cultural adaptation heuristic framework described by Barrera and colleagues is applied to the adaptation of a physical activity evidence-based intervention with adult Somali women. Widespread changes were required to ensure program feasibility and acceptability, including the reduction of assessment protocols and changes discordant with current trends in physical activity research. The cultural adaptation of evidence-based interventions offers an important mechanism for reducing health disparities. Improved reporting standards, assessment of features relevant to underserved communities, and greater funding requirements to ensure better representation are needed to promote more widespread access for all people. PMID- 27558246 TI - Risk of gestational hypertension and preeclampsia in women who discontinued or continued antidepressant medication use during pregnancy. AB - PURPOSE: This study aimed to examine the association between discontinued and continued use of antidepressants and risk for gestational hypertension (GH) and preeclampsia (PE). METHODS: Data from the MotherToBaby pregnancy studies from 2004 to 2014 were analyzed to compare women who discontinued antidepressant use ?20 weeks of gestation (discontinuers) and women who continued antidepressant use >=20 weeks of gestation (continuers) to non-users for risk of GH (blood pressure >=140/90 mmHg on two or more occasions at >=20 weeks of gestation) and PE (GH with proteinuria). Maternal data, including exposures and study outcomes, were collected through multiple phone interviews. Medical records were used to validate outcomes. Odds ratios (ORs) and 95 % confidence intervals were estimated using logistic regression. Risk for GH and PE were also assessed within antidepressant drug classes. RESULTS: Data from 3471 women were analyzed. Continuers were significantly at risk for GH (adjusted odds ratios (aOR) 1.83; 95 % CI 1.05, 3.21) after adjustment. Analyses by drug class showed that continued use of serotonin-norepinephrine reuptake inhibitors (SNRI) increased risk for GH; however, of the 21 women who continued to use SNRI, only 3 developed GH. Continuers who used two or more antidepressant drug classes had increased risk for PE. Selective serotonin reuptake inhibitors or other antidepressant use was not associated with increased risk for GH or PE. No significant associations with PE or GH were found for discontinuers. CONCLUSIONS: Results suggest that women who continued to use antidepressants in the second half of pregnancy are at risk for GH and PE. No significant association was found among discontinuers. PMID- 27558247 TI - "This thing of testing our blood is really very important": a qualitative study of primary care laboratory services in Tete Province, Mozambique. AB - BACKGROUND: Laboratory services are essential for diagnosis and management of patients, and for disease control, and should form an integral part of primary health services capable of contributing to Universal Health Coverage. Nevertheless, they remain among the most neglected health services in resource poor countries, including Mozambique. The Health Directorate of Tete Province, Mozambique, developed this study to analyse the role and perceived impact of laboratory services in primary healthcare on access, perceived service quality and disease control. METHODS: Qualitative research was done in three primary health facilities with and three without a laboratory in Tete Province, purposively sampled for their available services, accessibility and size. The role of the laboratory in primary health care was explored by reviewing documents, including records and monthly reports, interviews with clinicians, laboratory technicians and key informants (community leaders), and through focus group discussions with beneficiaries. Numeric data were summarized in MicrosoftTM Excel. Qualitative data were analysed for content within generated categories, interpreted within the concept of Universal Health Coverage, cross validated between the researchers. RESULTS: The results showed a greater use of health services, with more frequent diagnosis and monitoring of prevalent diseases, in facilities with a laboratory as compared with facilities without. Clinicians, patients and community leaders in facilities with a laboratory perceived an improved possibility of diagnosing and treating prevalent diseases, resulting in greater satisfaction with the provided services. Laboratory technicians confirmed that patients appreciated having access to laboratory tests. Clinicians, patients and community leaders in facilities without a laboratory protested its lack, claiming that it increased the likelihood of costly referrals, delays and even deaths. CONCLUSIONS: The study concluded that the laboratory plays an important role in primary level health facilities, as it is associated with greater utilization and perceived higher quality of services. Lack of a laboratory hampers patient management, disease control and financial risk protection. Expansion of the clinical laboratory system at primary level health facilities should be a properly funded priority of the national health system in Mozambique and similar countries. PMID- 27558248 TI - Donor faecal transplantation is highly curative in recurrent C difficile infection, trial finds. PMID- 27558249 TI - The rapid kinetics of optimal treatment with subcutaneous methotrexate in early inflammatory arthritis: an observational study. AB - BACKGROUND: Methotrexate (MTX) is standard treatment for RA. Absorption is better in subcutaneous MTX (scMTX), which may impact speed of onset. In RA, earlier time to remission improves long-term results. Our objectives were to determine rapidity of response of subcutaneous methotrexate in early rheumatoid arthritis. METHODS: The change in several disease activity measures (including DAS28) from 0 to 6 weeks (early period) and 6 to 12 weeks (late period) was compared. The proportion achieving DAS28/CDAI/SDAI remission and/or low disease activity state was also compared. RESULTS: One hundred three patients were included from a single site between 2008 and 2014. All received MTX (98.0 % scMTX, 98 % 25 mg/week). There were no dropouts. There was a significantly greater early change in DAS28 (-1.9 vs. -0.2, p < 0.00); this effect was seen for several outcome measures. By 6 weeks, 59 % had achieved either DAS28 remission or low disease activity state, with 74 % achieving either state by 12 weeks. There were a larger proportion of patients achieving CDAI and DAS28 remission in the early versus late period (p < 0.0002 for both). There was significant improvement when using combination MTX and HCQ, however sample size was small (n = 9). The use of intra articular steroids with MTX yielded the most disease measures that demonstrated early significant improvement. CONCLUSION: Subcutaneous MTX is rapid, as the change in many disease activity scores was significantly greater between 0-6 weeks compared to 6-12 weeks. Combination MTX + HCQ gave added value, although generalizability is limited by combination cohort sample size. Intra-articular steroid injections may contribute to the early effect. PMID- 27558251 TI - Proton therapy for the management of uveal melanoma and other ocular tumors. AB - Proton beam radiotherapy of uveal melanoma and other malignant and benign ocular tumors has shown tremendous development and success over the past four decades. Proton beam is associated with the lowest overall risk of local tumor recurrence in uveal melanoma, compared with other eye-conserving forms of primary treatment. Proton beam is also utilized for other malignant and benign tumors as primary, salvage, or adjuvant treatment with combined modality therapy. The physical characteristics of proton therapy allows for uniform dose distribution, minimal scatter, and sharp dose fall off making it an ideal therapy for ocular tumors in which critical structures lay in close proximity to the tumor. High radiation doses can be delivered to tumors with relative sparing of adjacent tissues from collateral damage. Proton beam therapy for ocular tumors has resulted in overall excellent chances for tumor control, ocular conservation, and visual preservation. PMID- 27558250 TI - A generic, cost-effective, and scalable cell lineage analysis platform. AB - Advances in single-cell genomics enable commensurate improvements in methods for uncovering lineage relations among individual cells. Current sequencing-based methods for cell lineage analysis depend on low-resolution bulk analysis or rely on extensive single-cell sequencing, which is not scalable and could be biased by functional dependencies. Here we show an integrated biochemical-computational platform for generic single-cell lineage analysis that is retrospective, cost effective, and scalable. It consists of a biochemical-computational pipeline that inputs individual cells, produces targeted single-cell sequencing data, and uses it to generate a lineage tree of the input cells. We validated the platform by applying it to cells sampled from an ex vivo grown tree and analyzed its feasibility landscape by computer simulations. We conclude that the platform may serve as a generic tool for lineage analysis and thus pave the way toward large scale human cell lineage discovery. PMID- 27558252 TI - Proton therapy for tumors of the base of the skull. AB - Relative to conventional photon irradiation, proton therapy has distinct advantages in its ability to more precisely target tumor while shielding adjacent normal tissues. In the setting of skull base tumors, proton therapy plays a critical role in the dose-escalation required for optimal tumor control of chordomas, chondrosarcomas, and malignancies of the paranasal sinuses and nasal cavity. For benign tumors such as craniopharyngiomas, pituitary adenomas and meningiomas, proton therapy can limit long-term adverse effects, such as secondary malignancies. This review summarizes published literature to date regarding the role of proton therapy in skull base tumors and introduces emerging proton therapy approaches such as pencil-beam scanning (PBS). PMID- 27558254 TI - Proton beam therapy for the treatment of esophageal cancer. AB - Radiation therapy (RT) has become an important component in the curative management of esophageal cancer (EC) worldwide. Since most of the ECs seen in the Western hemisphere (i.e., Europe and the United States) are located in the mid- to distal-esophageal locations, heart and lungs invariably receive significant radiation doses. Much of the normal tissue exposure could be reduced with the utilization of advanced radiation technologies, notably intensity modulated radiation therapy (IMRT). Proton beam therapy (PBT) provides the ability to even further reduce normal tissue exposure because of its lack of exit dose, which is expected to provide clinically meaningful benefit for at least some EC patients. Herein, we provide an overview of the comparative effectiveness of proton versus photon therapy, summarize the published clinical experience, and describe the future outlook of PBT development in EC. PMID- 27558255 TI - Controversies in proton therapy for prostate cancer. AB - Proton therapy (PT) for prostate cancer has been a subject of controversy over the past two decades. Because of its dosimetric advantages when compared to conventional radiation, PT has the potential to improve the therapeutic ratio in the management of prostate cancer by decreasing toxicity and improving disease control. Nevertheless, its higher costs and the current lack of level I evidence documenting improved clinical outcomes have led some to question its cost effectiveness. A number of new PT centers have been built over the past decade, leading many stakeholders, including patients, physicians, and insurers, to demand comparative effectiveness data to support its current use. In this review, we summarize the results of recently published studies that support the safety and efficacy of PT in the treatment of prostate cancer. We also review the available cost-effectiveness data for PT and discuss the future of PT, including the current randomized trial comparing PT to intensity-modulated radiation therapy and the need for additional research that may help to establish the relative benefit of PT when compared to photon-based radiation therapy. PMID- 27558253 TI - Novel applications of proton therapy in breast carcinoma. AB - This review will focus on the indications, clinical experience, and technical considerations of proton beam radiation therapy in the treatment of patients with breast cancer. For patients with early stage disease, proton therapy delivers less dose to non-target breast tissue for patients receiving partial breast irradiation (PBI) therapy, which may result in improved cosmesis but requires further investigation. For patients with locally advanced breast cancer requiring treatment to the regional lymph nodes, proton therapy allows for an improved dosimetric profile compared with conventional photon and electron techniques. Early clinical results demonstrate acceptable toxicity. The possible reduction in cardiopulmonary events as a result of reduced dose to organs at risk will be tested in a randomized control trial of protons vs. photons. PMID- 27558256 TI - Training a new generation of surgeons worldwide who are also oncologists. PMID- 27558257 TI - Moving forward: CCO is indexed in Emerging Sources Citation Index. PMID- 27558258 TI - Regulation by L channels of Ca(2+)-evoked secretory responses in ouabain-treated chromaffin cells. AB - It is known that the sustained depolarisation of adrenal medullary bovine chromaffin cells (BCCs) with high K(+) concentrations produces an initial sharp catecholamine release that subsequently fades off in spite depolarisation persists. Here, we have recreated a sustained depolarisation condition of BCCs by treating them with the Na(+)/K(+) ATPase blocker ouabain; in doing so, we searched experimental conditions that permitted the development of a sustained long-term catecholamine release response that could be relevant during prolonged stress. BCCs were perifused with nominal 0Ca(2+) solution, and secretion responses were elicited by intermittent application of short 2Ca(2+) pulses (Krebs-HEPES containing 2 mM Ca(2+)). These pulses elicited a biphasic secretory pattern with an initial 30-min period with secretory responses of increasing amplitude and a second 30-min period with steady-state, non-inactivating responses. The initial phase was not due to gradual depolarisation neither to gradual increases of the cytosolic calcium transients ([Ca(2+)]c) elicited by 2Ca(2+) pulses in BBCs exposed to ouabain; both parameters increased soon after ouabain addition. Nuifedipine blocked these responses, and FPL64176 potentiated them, suggesting that they were triggered by Ca(2+) entry through non inactivating L-type calcium channels. This was corroborated by nifedipine-evoked blockade of the L-type Ca(2+) channel current and the [Ca(2+)]c transients elicited by 2Ca(2+) pulses. Furthermore, the plasmalemmal Na(+)/Ca(2+) exchanger (NCX) blocker SEA0400 caused a mild inhibition followed by a large rebound increase of the steady-state secretory responses. We conclude that these two phases of secretion are mostly contributed by Ca(2+) entry through L calcium channels, with a minor contribution of Ca(2+) entry through the reverse mode of the NCX. PMID- 27558260 TI - Reproducibility of choroidal thickness measurements in subjects on 3 spectral domain optical coherence tomography machines. AB - The purpose of this study was to investigate the reproducibility of choroidal thickness measurements in normal subjects on 3 spectral domain optical coherence tomography instruments, namely: Zeiss Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA), Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany), and Optovue RTVue (Optovue Inc., Fremont, CA). This cross-sectional non interventional study was performed in a single institution. Images were obtained in 47 eyes of 47 healthy volunteers which age ranged between 23 and 72 without ocular pathology. All subjects were imaged on the fovea using Cirrus HD 1-line raster, Spectralis enhanced depth imaging, and RTVue retina-cross. The choroid was measured subfoveally and at intervals of 500 um from the fovea nasally and temporally up to 2500 um. Paired t test, modified Bland-Altman plot, and Pearson's correlation were used to compare the results. There is no significant difference between the systems for any measurement within 2500 um either side of the fovea for most points. Inter-observer correlation was strong for RTVue, and moderate in both Cirrus and Spectralis. PMID- 27558259 TI - Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment. AB - BACKGROUND: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. METHODS: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival. RESULTS: Gal-7 was constantly downregulated in our meta analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. CONCLUSIONS: Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal 7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected. PMID- 27558261 TI - [Thoracoabdominal aortic aneurysm]. AB - Thoracoabdominal aortic aneurysms (TAAA) are rare events with an incidence of 5.9 cases per 100,000 persons per year. In Germany approximately 940 TAAA procedures are performed annually. The cause of TAAA is mostly degenerative but they can also occur on the basis of an aortic dissection or connective tissue disease (e. g. Marfan's syndrome). Patients often have severe comorbidities and suffer from hypertension, coronary heart disease or chronic obstructive pulmonary disease, mostly as a result of smoking. Operative treatment is indicated when the maximum aortic diameter has reached 6 cm (> 5 cm in patients with connective tissue disease) or the aortic diameter rapidly increases (> 5 mm/year). Treatment options are open surgical aortic repair with extracorporeal circulation, endovascular repair with branched/fenestrated endografts and parallel grafts (chimneys) or a combination of open and endovascular procedures (hybrid procedures). Mortality rates after both open and endovascular procedures are approximately 8 % depending on the extent of the repair. Furthermore, there are relevant risks of complications, such as paraplegia (up to 20 %) and the necessity for dialysis. In recent years several approaches to minimize these risks have been proposed. Besides cardiopulmonary risk evaluation, clinical assessment of patients by the physician with respect to the patient-specific anatomy influences the allocation of patients to one treatment option or another. Surgery of TAAA should ideally be performed in high-volume centers in order to achieve better results. PMID- 27558262 TI - Preclinical evaluation of [111 In]MICA-401, an activity-based probe for SPECT imaging of in vivo uPA activity. AB - Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 are key players in cancer invasion and metastasis. Both uPA and PAI-1 have been described as prognostic biomarkers; however, non-invasive methods measuring uPA activity are lacking. We developed an indium-111 (111 In)-labelled activity-based probe to image uPA activity in vivo by single photon emission computed tomography (SPECT). A DOTA-conjugated uPA inhibitor was synthesized and radiolabelled with 111 In ([111 In]MICA-401), together with its inactive, hydrolysed form ([111 In]MICA 402). A biodistribution study was performed in mice (healthy and tumour-bearing), and tumour-targeting properties were evaluated in two different cancer xenografts (MDA-MB-231 and HT29) with respectively high and low levels of uPA expression in vitro, with either the active or hydrolysed radiotracer. MicroSPECT was performed 95 h post injection followed by ex vivo biodistribution. Tumour uptake was correlated with human and murine uPA expression determined by ELISA and immunohistochemistry (IHC). Biodistribution data with the hydrolysed probe [111 In]MICA-402 showed almost complete clearance 95 h post injection. The ex vivo biodistribution and SPECT data with [111 In]MICA-401 demonstrated similar tumour uptakes in the two models: ex vivo 5.68 +/- 1.41%ID/g versus 5.43 +/- 1.29%ID/g and in vivo 4.33 +/- 0.80 versus 4.86 +/- 1.18 for MDA-MB-231 and HT-29 respectively. Human uPA ELISA and IHC showed significantly higher uPA expression in the MDA-MB-231 tumours, while mouse uPA staining revealed similar staining intensities of the two tumours. Our data demonstrate non-invasive imaging of uPA activity in vivo, although the moderate tumour uptake and hence potential clinical translation of the radiotracer warrants further investigation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27558263 TI - Development of a Cavity Disinfectant Containing Antibacterial Monomer MDPB. AB - An experimental cavity disinfectant (ACC) that is intended to be used for various direct and indirect restorations was prepared by adding an antibacterial monomer 12-methacryloyloxydodecylpyridinum bromide (MDPB) at 5% into 80% ethanol. The antibacterial effectiveness of ACC and its influences on the bonding abilities of resin cements were investigated. To examine the antibacterial activity of unpolymerized MDPB, the minimum inhibitory and bactericidal concentrations (MIC and MBC) were determined for Streptococcus mutans, Lactobacillus casei, Actinomyces naeslundii, Parvimonas micra, Enterococcus faecalis, Fusobacterium nucleatum, and Porphyromonas gingivalis Antibacterial activities of ACC and the commercial cavity disinfectant containing 2% chlorhexidine and ethanol (CPS) were evaluated by agar disk diffusion tests through 7 bacterial species and by MIC and MBC measurement for S. mutans The effects of ACC and CPS to kill bacteria in dentinal tubules were compared with an S. mutans-infected dentin model. Shear bond strength tests were used to examine the influences of ACC on the dentin bonding abilities of a self-adhesive resin cement and a dual-cure resin cement used with a primer. Unpolymerized MDPB showed strong antibacterial activity against 7 oral bacteria. ACC produced inhibition zones against all bacterial species similar to CPS. For ACC and CPS, the MIC value for S. mutans was identical, and the MBC was similar with only a 1-step dilution difference (1:2). Treatment of infected dentin with ACC resulted in significantly greater bactericidal effects than CPS (P < 0.05, analysis of variance and Tukey's honest significant difference test). ACC showed no negative influences on the bonding abilities to dentin for both resin cements, while CPS reduced the bond strength of the self-adhesive resin cement (P < 0.05). This study clarified that the experimental cavity disinfectant containing 5% MDPB is more effective in vitro than the commercially available chlorhexidine solution to eradicate bacteria in dentin, without causing any adverse influences on the bonding abilities of resinous luting cements. PMID- 27558264 TI - MMP20 Proteolysis of Native Amelogenin Regulates Mineralization In Vitro. AB - Recent studies have shown that native phosphorylated full-length porcine amelogenin (P173) and its predominant cleavage product (P148) can inhibit spontaneous calcium phosphate formation in vitro by stabilizing an amorphous calcium phosphate (ACP) precursor phase. Since full-length amelogenin undergoes proteolysis by matrix metalloproteinase 20 (MMP20, enamelysin) soon after secretion, the present study was conducted to assess the effect of amelogenin proteolysis on calcium phosphate formation. Calcium and phosphate were sequentially added to protein solutions without and with added MMP20 (ratio = 200:1) under physiological-like conditions of ionic strength (163 mM) in 50 mM Tris-HCl (pH 7.4) at 37 degrees C. Protein degradation with time was assessed by gel-electrophoresis, and mineral products formed were characterized by transmission electron microscopy (TEM). MMP20 was found to cleave P173 to primarily generate P148, along with P162, P46-148, and P63/64-148. In sharp contrast, MMP20 did not cleave P148. In addition, the formation of well-aligned bundles of enamel-like hydroxyapatite (HA) crystals was promoted in the presence of P173 with added MMP20, while only ACP particles were seen in the absence of MMP20. Although P148 was found to have a somewhat lower capacity to stabilize ACP and prevent HA formation compared with P173 in the absence of MMP20, essentially no HA formation was observed in the presence of somewhat higher concentrations of P148 regardless of MMP20 addition, due to the lack of observed protein proteolysis. Present findings suggest that ACP transformation to ordered arrays of enamel crystals may be regulated in part by the proteolysis of full-length native amelogenin, while the predominant amelogenin degradation product in developing enamel (e.g., P148) primarily serves to prevent uncontrolled mineral formation during the secretory stage of amelogenesis. PMID- 27558265 TI - Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes. AB - Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis. PMID- 27558266 TI - Depression Screening in Diabetes Care to Improve Outcomes: Are We Meeting the Challenge? AB - PURPOSE: Evidence-based guidelines recommend regular depression screening among individuals with type 2 diabetes mellitus (T2DM). The purpose of this study is to examine depression screening patterns among a primary care population with T2DM, through use of the Patient Health Questionnaire-9 (PHQ-9). METHODS: In total, 1817 patients with T2DM were analyzed through a retrospective observational study at 2 sites, a regional health center and a federally qualified health center (FQHC). The T2DM sample was divided into those with and without a major depressive disorder (MDD) diagnosis. Depression screening rates and depression severity were assessed through the PHQ-9. RESULTS: Both sites had higher rates of PHQ-9 screening among individuals with a history of MDD (64.82%) vs those without MDD (11.39%). Individuals from the FQHC without a history of depression had a higher mean PHQ-9 score (10.11) than those with a previous MDD diagnosis at both RHS and FQHC (7.16 and 9.85, respectively). CONCLUSIONS: Depression screening rates among individuals with diabetes and no history of MDD were remarkably low. Patients with diabetes but no MDD diagnosis who sought health care at a FQHC clinic had more depressive symptoms than those with a history of MDD at both sites. Individuals with diabetes and who have a MDD diagnosis are much more likely to receive regular depression screening than those without MDD, which leaves a substantial proportion of patients with undetected depression. Depression screening must be enhanced for all individuals with diabetes, particularly for low-income individuals and those without a previous diagnosis of MDD. PMID- 27558268 TI - Evidence-based (S3) guidelines for diagnostics and treatment of venous leg ulcers. PMID- 27558267 TI - Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region. AB - BACKGROUND: Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceara State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis. METHODS: The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceara, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents. RESULTS: We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceara State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceara (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceara have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast. CONCLUSIONS: The high frequency of pycnodysostosis in Ceara State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceara, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceara, suggestive of a founder effect. PMID- 27558269 TI - Did the English strategy reduce inequalities in health? A difference-in difference analysis comparing England with three other European countries. AB - BACKGROUND: Between 1997 and 2010, the English government pursued an ambitious programme to reduce health inequalities, the explicit and sustained commitment of which was historically and internationally unique. Previous evaluations have produced mixed results. None of these evaluations have, however, compared the trends in health inequalities within England with those in other European countries. We carried out an innovative analysis to assess whether changes in trends in health inequalities observed in England after the implementation of its programme, have been more favourable than those in other countries without such a programme. METHODS: Data were obtained from nationally representative surveys carried out in England, Finland, the Netherlands and Italy for years around 1990, 2000 and 2010. A modified difference-in-difference approach was used to assess whether trends in health inequalities in 2000-2010 were more favourable as compared to the period 1990-2000 in England, and the changes in trends in inequalities after 2000 in England were then compared to those in the three comparison countries. Health outcomes were self-assessed health, long-standing health problems, smoking status and obesity. Education was used as indicator of socioeconomic position. RESULTS: After the implementation of the English strategy, more favourable trends in some health indicators were observed among low-educated people, but trends in health inequalities in 2000-2010 in England were not more favourable than those observed in the period 1990-2000. For most health indicators, changes in trends of health inequalities after 2000 in England were also not significantly different from those seen in the other countries. CONCLUSIONS: In this rigorous analysis comparing trends in health inequalities in England both over time and between countries, we could not detect a favourable effect of the English strategy. Our analysis illustrates the usefulness of a modified difference-in-difference approach for assessing the impact of policies on population-level health inequalities. PMID- 27558270 TI - Factors associated with Toxoplasma gondii infection in confined farrow-to-finish pig herds in western France: an exploratory study in 60 herds. AB - BACKGROUND: Infection by Toxoplasma gondii postnatally can occur after ingestion of contaminated meat or water (tissue cysts/oocysts). In Europe, percentage of meat borne infections is estimated between 30 and 63 %, out of which pork makes the most important source. The aim of this study was to (i) investigate the seroprevalence of T. gondii in intensive pig farms from western France; and (ii) identify the risk factors associated with seropositivity. METHODS: Data were collected between November 2006 and February 2008 in 60 intensive farrow-to finish farms, where sera were taken from 3595 fattening pigs, weaned and suckling piglets. Information about three classes of potential seropositivity risk factors were obtained through a questionnaire concerning: (i) breeding characteristics; (ii) farm management; and (iii) husbandry and hygiene. The modified agglutination test (MAT) was used for detection of specific anti T. gondii antibodies in pig sera, starting from 1/6 dilution. RESULTS: The overall proportion of seropositive animals was 6.9 %, but the proportion of herds with at least one positive pig was 100 %. Multivariate logistic mixed model showed an increased seropositivity risk in weaned compared to suckling piglets, and a decreasing risk for mid-sized and large farms. The presence of a Danish entry facility, that clearly separates clean and dirty areas, had a protective effect on T. gondii seropositivity as well. CONCLUSIONS: The observed proportion of herds with at least one T. gondii seropositive animal provides further evidence that even in confined conditions of pig breeding, infection occurs, and is common. The highest risk for acquiring T. gondii is at the end of weaning period. Smaller confined pig farms demonstrate higher T. gondii seropositivity levels. This study also showed that Danish entry on farm buildings provides effective protection against T. gondii. PMID- 27558271 TI - How do medical specialists value their own intercultural communication behaviour? A reflective practice study. AB - BACKGROUND: Intercultural communication behaviour of doctors with patients requires specific intercultural communication skills, which do not seem structurally implemented in medical education. It is unclear what motivates doctors to apply intercultural communication skills. We investigated how purposefully medical specialists think they practise intercultural communication and how they reflect on their own communication behaviour. METHODS: Using reflective practice, 17 medical specialists independently watched two fragments of videotapes of their own outpatient consultations: one with a native patient and one with a non-native patient. They were asked to reflect on their own communication and on challenges they experience in intercultural communication. The interviews were open coded and analysed using thematic network analysis. RESULTS: The participants experienced only little differences in their communication with native and non-native patients. They mainly mentioned generic communication skills, such as listening and checking if the patient understood. Many participants experienced their communication with non-native patients positively. The participants mentioned critical incidences of intercultural communication: language barriers, cultural differences, the presence of an interpreter, the role of the family and the atmosphere. CONCLUSION: Despite extensive experience in intercultural communication, the participants of this study noticed hardly any differences between their own communication behaviour with native and non-native patients. This could mean that they are unaware that consultations with non-native patients might cause them to communicate differently than with native patients. The reason for this could be that medical specialists lack the skills to reflect on the process of the communication. The participants focused on their generic communication skills rather than on specific intercultural communication skills, which could either indicate their lack of awareness, or demonstrate that practicing generic communication is more important than applying specific intercultural communication. They mentioned well known critical incidences of ICC: language barriers, cultural differences, the presence of an interpreter, the role of the family and the atmosphere. Nevertheless, they showed a remarkably enthusiastic attitude overall was noteworthy. A strategy to make doctors more aware of their intercultural communication behaviour could be a combination of experiential learning and ICC training, for example a module with reflective practice. PMID- 27558273 TI - Damage by Tibraca limbativentris Stal (Pentatomidae) to Upland Rice Cultivated in Amazon Rainforest Region (Brazil) at Different Growth Stages. AB - In this study, we evaluated the damage caused in the field by Tibraca limbativentris Stal adults at different levels of infestation (0, 1, 2, and 4 stink bugs) per three rice plants during three growth stages (V8, V13, and R4 stages) of upland rice cultivated in southwestern of Para State, Amazon Rainforest region, Brazil. Heading time (panicle exertion) was affected by T. limbativentris infestations mainly in the vegetative stage and the whiteheads percentage in treatments ranged from 18.2 to 38%. The dead hearts percentages varied between 0 and 21.5%, and the mean number of primary branches (ramifications) ranged from 5.9 +/- 0.4 to 12.3 +/- 0.2. The number of empty spikelets was only affected in infestations with four insects/three plants, while the quantity of filled grains per panicle was affected only when infestations occurred during the vegetative stage. The total number of spikelets (filled + empty) per panicle decreased significantly in all phenological stages, and the percentage of damage ranged from 17 to 44% among treatments. Based on the proportion of damage observed, we suggest doubling the number of insects presently used as action threshold to 2 and 4 stink bugs per 15 stalks sampled for the vegetative stage, and of 1 or 2 stink bugs per 15 stalks sampled at the beginning of reproductive stage (R3/R4). Also, the field should be monitored during the entire vegetative stage, since most damage was observed in this phenological stage. PMID- 27558272 TI - Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. AB - The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease. PMID- 27558274 TI - Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review. AB - Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score <=2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS. PMID- 27558275 TI - Visualization of Sweat Fingerprints on Various Surfaces Using a Conjugated Polyelectrolyte. AB - A conformation-variable conjugated polyelectrolyte responding to oppositely charged biomolecules was examined as an imaging agent for the detection of latent fingerprints (LFPs). Sulfonated poly(diphenylacetylene) (SPDPA) produces high resolution fluorescence (FL) LFP images by simple wetting of the target objects with the polymer solution without any additional treatment. SPDPA readily interacts with LFP sweat components (especially amino acids) via electrostatic interactions, leading to significantly enhanced FL images in a "turn-on" mode. The FL emission enhancement was examined in a model reaction between SPDPA and an amino acid standard. Visualization with SPDPA is effective on various surfaces, including both rough (paper) and smooth (glass and plastic) ones. Moreover, SPDPA readily interacts with extremely thin sweat LFPs, especially on smooth glass surfaces. PMID- 27558276 TI - Magma transfer at Campi Flegrei caldera (Italy) before the 1538 AD eruption. AB - Calderas are collapse structures related to the emptying of magmatic reservoirs, often associated with large eruptions from long-lived magmatic systems. Understanding how magma is transferred from a magma reservoir to the surface before eruptions is a major challenge. Here we exploit the historical, archaeological and geological record of Campi Flegrei caldera to estimate the surface deformation preceding the Monte Nuovo eruption and investigate the shallow magma transfer. Our data suggest a progressive magma accumulation from ~1251 to 1536 in a 4.6 +/- 0.9 km deep source below the caldera centre, and its transfer, between 1536 and 1538, to a 3.8 +/- 0.6 km deep magmatic source ~4 km NW of the caldera centre, below Monte Nuovo; this peripheral source fed the eruption through a shallower source, 0.4 +/- 0.3 km deep. This is the first reconstruction of pre-eruptive magma transfer at Campi Flegrei and corroborates the existence of a stationary oblate source, below the caldera centre, that has been feeding lateral eruptions for the last ~5 ka. Our results suggest: 1) repeated emplacement of magma through intrusions below the caldera centre; 2) occasional lateral transfer of magma feeding non-central eruptions within the caldera. Comparison with historical unrest at calderas worldwide suggests that this behavior is common. PMID- 27558277 TI - Ovarian cancer. PMID- 27558278 TI - Immunologic characteristics of human gingival fibroblasts in response to oral bacteria. AB - BACKGROUND AND OBJECTIVE: There is ample evidence that gingival fibroblasts (GFs) participate in the immune response to oral bacteria and serve as immune regulatory cells. The objective of this study was to investigate the innate immune response of GFs to oral bacteria. MATERIAL AND METHODS: Human GFs were cocultured with relatively less-pathogenic (Leptotrichia wadei, Fusobacterium nucleatum and Campylobacter gracilis) and pathogenic red-complex bacteria. The expression of mRNA for antimicrobial peptides [AMPs; namely human beta defensins (HBDs)], chemokines with antimicrobial activity [chemokine C-X-C motif (CXCL)10, CXCL11 and chemokine C-C motif ligand 20 (CCL20)] and proinflammatory mediators [interleukin (IL)6 and IL8] and the levels of CXCL11, CCL20, IL-6 and IL-8 accumulated in supernatants were analyzed using real-time PCR and ELISA, respectively. The proteolytic activities of CXCL11, CCL20, IL-6 and IL-8 produced by six species of bacteria were also determined. RESULTS: The relatively less pathogenic bacteria strongly up-regulated the expression of antimicrobial chemokines and proinflammatory mediators, whereas the red-complex bacteria stimulated low levels, or often suppressed, expression of these factors. Regarding the regulation of AMPs, the inhibition of HBD3, HBD106 and HBD107 mRNAs by Porphyromonas gingivalis was noticeable; however, differences between the two bacterial groups were not conspicuous. Differential degradation of proteins by the six bacterial species was observed: P. gingivalis and Treponema denticola degraded proteins well, whereas the other species degraded proteins to a relatively lower degree. CONCLUSION: The invasion of red-complex bacteria into gingival connective tissue can suppress the immune response of GFs and can be a source of persistent infection in connective tissue. PMID- 27558279 TI - Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening. AB - BACKGROUND: Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC). METHODS: This is a case control study of prospectively-collected biobank samples comprising preoperative plasma from 32 women with HGSOC (16 'early cancer' (FIGO I-II) and 16 'advanced cancer' (FIGO III-IV)) and 32 benign controls. Plasma DNA from cases and controls were sequenced using a commercial NIPT platform and chromosome dosage measured. Sequencing data were blindly analyzed with two methods: (1) Subchromosomal changes were called using an open source algorithm WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR). Genomic gains or losses >= 15 Mb were prespecified as "screen positive" calls, and mapped to recurrent copy number variations reported in an ovarian cancer genome atlas. (2) Selected whole chromosome gains or losses were reported using the routine NIPT pipeline for fetal aneuploidy. RESULTS: We detected 13/32 cancer cases using the subchromosomal analysis (sensitivity 40.6 %, 95 % CI, 23.7-59.4 %), including 6/16 early and 7/16 advanced HGSOC cases. Two of 32 benign controls had subchromosomal gains >= 15 Mb (specificity 93.8 %, 95 % CI, 79.2-99.2 %). Twelve of the 13 true positive cancer cases exhibited specific recurrent changes reported in HGSOC tumors. The NIPT pipeline resulted in one "monosomy 18" call from the cancer group, and two "monosomy X" calls in the controls. CONCLUSIONS: Low coverage plasma DNA sequencing used for prenatal testing detected 40.6 % of all HGSOC, including 38 % of early stage cases. Our findings demonstrate the potential of a high throughput sequencing platform to screen for early HGSOC in plasma based on characteristic multiple segmental chromosome gains and losses. The performance of this approach may be further improved by refining bioinformatics algorithms and targeting selected cancer copy number variations. PMID- 27558280 TI - The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure. AB - In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d. PMID- 27558281 TI - Comparative virulence of in vitro-cultured primate- and pig-associated Helicobacter suis strains in a BALB/c mouse and a Mongolian gerbil model. AB - BACKGROUND: Helicobacter suis (H. suis) is the most prevalent gastric non-H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of nonhuman primates. The aim of this study was to obtain better insights into potential differences between pig- and primate-associated H. suis strains in virulence and pathogenesis. MATERIALS AND METHODS: In vitro-isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis), and rhesus monkeys (Macaca mulatta) were used for intragastric inoculation of BALB/c mice and Mongolian gerbils. Nine weeks and six months later, samples of the stomach of inoculated and control animals were taken for PCR analysis and histopathological examination. RESULTS: The cynomolgus monkey-associated H. suis strain only colonized the stomach of mice, but not of Mongolian gerbils. All other H. suis strains colonized the stomach in both rodent models. In all colonized animals, severe gastric inflammation was induced. Gastric lymphoid follicles and destruction of the antral epithelium were observed in infected gerbils, but not in mice. Infection with both pig- and primate-associated H. suis strains evoked a similar marked Th17 response in mice and gerbils, accompanied by increased CXCL 13 expression levels. CONCLUSIONS: Apart from the cynomolgus monkey-associated strain which was unable of colonizing the stomach of Mongolian gerbils, no substantial differences in virulence were found in rodent models between in vitro cultured pig-associated, cynomolgus monkey-associated and rhesus monkey associated H. suis strains. The experimental host determines the outcome of the immune response against H. suis infection, rather than the original host. PMID- 27558283 TI - Epidemiology, clinical presentation and therapeutic approach in a multicentre series of dissecting cellulitis of the scalp. PMID- 27558282 TI - In vitro evaluation of the antiviral activity of methylglyoxal against influenza B virus infection. AB - Influenza A and B virus infections are serious public health concerns globally. However, the concerns regarding influenza B infection have been underestimated. The currently used anti-influenza drugs have not provided equal efficacy for both influenza A and B viruses. Susceptibility to neuraminidase (NA) inhibitors has been observed to be lower for influenza B viruses than for influenza A viruses. Moreover, the emergence of resistance to anti-influenza drugs underscores the need to develop new drugs. Recently, we reported that methylglyoxal (MGO) suppressed influenza A virus replication in a strain-independent manner. Therefore, we hypothesize that MGO exhibits anti-influenza activity against B strains. This study aimed to evaluate the anti-influenza viral activity of MGO against influenza B strains by using Madin-Darby canine kidney (MDCK) cells. Several types of influenza B viruses were used to determine the activity of MGO. The susceptibilities of influenza A and B viruses to NA inhibitors were compared. MGO inhibited influenza B virus replication, with 50% inhibitory concentrations ranging from 23-140 MUM, which indicated greater sensitivity of influenza B viruses than influenza A viruses. Our results show that MGO has potent inhibitory activity against influenza B viruses, including NA inhibitor-resistant strains. PMID- 27558284 TI - Characterization of mammary epithelial stem/progenitor cells and their changes with aging in common marmosets. AB - Age is the number one risk factor for breast cancer, yet the underlying mechanisms are unexplored. Age-associated mammary stem cell (MaSC) dysfunction is thought to play an important role in breast cancer carcinogenesis. Non-human primates with their close phylogenetic relationship to humans provide a powerful model system to study the effects of aging on human MaSC. In particular, the common marmoset monkey (Callithrix jacchus) with a relatively short life span is an ideal model for aging research. In the present study, we characterized for the first time the mammary epithelial stem/progenitor cells in the common marmoset. The MaSC-enriched cells formed four major types of morphologically distinct colonies when cultured on plates pre-seeded with irradiated NIH3T3 fibroblasts, and were also capable of forming mammospheres in suspension culture and subsequent formation of 3D organoids in Matrigel culture. Most importantly, these 3D organoids were found to contain stem/progenitor cells that can undergo self renewal and multi-lineage differentiation both in vitro and in vivo. We also observed a significant decrease of luminal-restricted progenitors with age. Our findings demonstrate that common marmoset mammary stem/progenitor cells can be isolated and quantified with established in vitro and in vivo assays used for mouse and human studies. PMID- 27558285 TI - The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis. AB - Immunotherapy is a novel treatment for advanced non-small cell lung cancer (NSCLC) patients. Immunotherapy includes two main broad classes of therapeutic vaccines and immune checkpoint inhibitors, as well as cytokines, biological response modifiers and cellular therapy. The present systematic review and meta analysis aims to evaluate the efficacy and safety of different classes of immunotherapy in patients with advanced NSCLC. Literature search was done on Medline, Embase and Cochrane Library. The primary endpoints were overall survival (OS) and grade >=3 adverse events. Twenty randomized controlled trials were finally identified in our study. Efficacy analysis indicated an improvement of OS in advanced NSCLC patients after treating by therapeutic vaccines and immune checkpoint inhibitors, but not for other immunomodulators. Safety analysis showed that immunotherapy was well-tolerated. All kinds of grade >=3 adverse events were similar between experimental group and control group except that neutropenia and thrombocytopenia had a higher incidence in patients received vaccines. In conclusion, immunotherapy is a promising treatment for advanced NSCLC patients. Our findings will be further confirmed and supplemented by several phase II and phase III RCTs which are going to complete in near future. PMID- 27558286 TI - Does ovulation induction and intrauterine insemination affect perinatal outcomes in singletons? AB - AIM: To evaluate the effect of solely intrauterine insemination on perinatal outcomes. METHODS: A total of 3830 OI/IUI cycles between January 2007 and December 2012 were included in the study. Three hundred and fifty-eight pregnancies following intrauterine insemination were encountered during the study period. Data from 246 pregnancies conceived through OI/IUI treatment were available. A total of 438 singletons with no maternal risk constituted the control group. The two groups were compared according to perinatal outcomes. RESULTS: There was a statistically significant difference between the groups in first trimester abortion and intrauterine demise. At least one or more perinatal adverse outcomes occurred in study and control groups with the rates of 38.4% and 18.5%, respectively. There were significant differences in preterm delivery rate and oligohydramnios between the groups. There were also significant differences in the rate of neonates with a birth weight < 2500 g and NICU. CONCLUSION: In general, women's health perspective, to have a pregnancy is the main target in infertility work-ups, but physicians should be aware of the risks and couples should be counseled that pregnancies after OI/IUI treatment even if singleton carries a risk of adverse perinatal outcome for both the mother and baby. PMID- 27558287 TI - A micromechanical comparison of human and porcine skin before and after preservation by freezing for medical device development. AB - Collecting human skin samples for medical research, including developing microneedle-based medical devices, is challenging and time-consuming. Researchers rely on human skin substitutes and skin preservation techniques, such as freezing, to overcome the lack of skin availability. Porcine skin is considered the best substitute to human skin, but their mechanical resemblance has not been fully validated. We provide a direct mechanical comparison between human and porcine skin samples using a conventional mechano-analytical technique (microindentation) and a medical application (microneedle insertion), at 35% and 100% relative humidity. Human and porcine skin samples were tested immediately after surgical excision from subjects, and after one freeze-thaw cycle at -80 degrees C to assess the impact of freezing on their mechanical properties. The mechanical properties of fresh human and porcine skin (especially of the stratum corneum) were found to be different for bulk measurements using microindentation; and both types of skin were mechanically affected by freezing. Localized in-plane mechanical properties of skin during microneedle insertion appeared to be more comparable between human and porcine skin samples than their bulk out-of-plane mechanical properties. The results from this study serve as a reference for future mechanical tests conducted with frozen human skin and/or porcine skin as a human skin substitute. PMID- 27558289 TI - CuAAC Click Reactions in the Gas Phase: Unveiling the Reactivity of Bis-Copper Intermediates. AB - Copper-catalysed azide alkyne cycloaddition (CuAAC) has been considered a breakthrough transformation over the last 15 years. Its debated mechanism arouses continuously growing interest. By means of a mass spectrometer modified ad hoc, the entire catalytic cycle of CuAAC reaction has been investigated in the gas phase. Ion-molecule reactions were performed inside the mass spectrometer to reproduce step-by-step, at a molecular level, the complete catalytic cycle of the click reaction. We successfully challenged the reactivity of elusive mono- and bis-copper intermediates by ion-molecule reactions leading to the production of mass-characterized triazole products, paving the way for detailed energetic studies to be performed in the gas phase. The structures of the relevant species, calculated at a DFT level, helped rationalise our experimental results. PMID- 27558288 TI - The Shigella ProU system is required for osmotic tolerance and virulence. AB - To cope with hyperosmotic stress encountered in the environments and in the host, the pathogenic as well as non-pathogenic microbes use diverse transport systems to obtain osmoprotectants. To study the role of Shigella sonnei ProU system in response to hyperosmotic stress and virulence, we constructed deletion and complementation strains of proV and used an RNAi approach to silence the whole ProU operon. We compared the response between wild type and the mutants to the hyperosmotic pressure in vitro, and assessed virulence properties of the mutants using gentamicin protection assay as well as Galleria mellonella moth larvae model. In response to osmotic stress by either NaCl or KCl, S. sonnei highly up regulates transcription of proVWX genes. Supplementation of betaine greatly elevates the growth of the wild type S. sonnei but not the proV mutants in M9 medium containing 0.2 M NaCl or 0.2 M KCl. The proV mutants are also defective in intracellular growth compared with the wild type. The moth larvae model of G. mellonella shows that either deletion of proV gene or knockdown of proVWX transcripts by RNAi significantly attenuates virulence. ProU system in S. sonnei is required to cope with osmotic stress for survival and multiplication in vitro, and for infection. PMID- 27558290 TI - How the World Changes By Going from One- to Two-Dimensional Polymers in Solution. AB - Scaling behavior of one-dimensional (1D) and two-dimensional (2D) polymers in dilute solution is discussed with the goal of stimulating experimental work by chemists, physicists, and material scientists in the emerging field of 2D polymers. The arguments are based on renormalization-group theory, which is explained for a general audience. Many ideas and methods successfully applied to 1D polymers are found not to work if one goes to 2D polymers. The role of the various states exhibiting universal behavior is turned upside down. It is expected that solubility will be a serious challenge for 2D polymers. Therefore, given the crucial importance of solutions in characterization and processing, synthetic concepts are proposed that allow the local bending rigidity and the molar mass to be tuned and the long-range interactions to be engineered, all with the goal of preventing the polymer from falling into flat or compact states. PMID- 27558291 TI - Two new dammarane-type triterpenoid saponins from ginseng medicinal fungal substance. AB - Two new triterpenoid saponins, namely ginsenoside Re8 (1) and notoginsenoside ST 8 (2), were isolated from ginseng medicinal fungal substance. Their structures were elucidated by spectroscopic data and chemical analysis. PMID- 27558292 TI - The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner. AB - Memory formation is a complex cognitive function regulated by coordinated synaptic and nuclear processes in neurons. In mammals, it is controlled by multiple molecular activators and suppressors, including the key signalling regulator, protein phosphatase 1 (PP1). Here, we show that memory control by PP1 involves the miR-183/96/182 cluster and its selective regulation during memory formation. Inhibiting nuclear PP1 in the mouse brain, or training on an object recognition task similarly increases miR-183/96/182 expression in the hippocampus. Mimicking this increase by miR-183/96/182 overexpression enhances object memory, while knocking-down endogenous miR-183/96/182 impairs it. This effect involves the modulation of several plasticity-related genes, with HDAC9 identified as an important functional target. Further, PP1 controls miR 183/96/182 in a transcription-independent manner through the processing of their precursors. These findings provide novel evidence for a role of miRNAs in memory formation and suggest the implication of PP1 in miRNAs processing in the adult brain. PMID- 27558293 TI - A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4. AB - The centrosome is the major microtubule-organizing centre of many cells, best known for its role in mitotic spindle organization. How the proteins of the centrosome are accurately assembled to carry out its many functions remains poorly understood. The non-membrane-bound nature of the centrosome dictates that protein-protein interactions drive its assembly and functions. To investigate this massive macromolecular organelle, we generated a 'domain-level' centrosome interactome using direct protein-protein interaction data from a focused yeast two-hybrid screen. We then used biochemistry, cell biology and the model organism Drosophila to provide insight into the protein organization and kinase regulatory machinery required for centrosome assembly. Finally, we identified a novel role for Plk4, the master regulator of centriole duplication. We show that Plk4 phosphorylates Cep135 to properly position the essential centriole component Asterless. This interaction landscape affords a critical framework for research of normal and aberrant centrosomes. PMID- 27558295 TI - Grain quality characteristics and dough rheological properties in Langdon durum wild emmer wheat chromosome substitution lines under nitrogen and water deficits. AB - BACKGROUND: Wild emmer wheat could serve as a source of novel variation in grain quality and stress resistance for wheat breeding. A set of Triticum durum-T. dicoccoides chromosome substitution lines [LDN(DIC)] and the parental recipient cv. Langdon grown under contrasting water and nitrogen availability in the soil was examined in this study to identify differences in grain quality traits and dough rheological properties. RESULTS: Significant genotypic variation was found among the materials for studied traits. This variation was also considerably affected by soil treatments and G * E interactions. The substitutions LDN(DIC-1A) and LDN(DIC-1B) showed separate differentiation in the composition of glutenin sub-units. The results indicated that primarily chromosome DIC-6B is stable source of an enhanced grain protein content and advantageous dough rheological properties. Similar features seem to be shown by the substitutions with the DIC 1A, DIC-2A and DIC-6A, but not under nitrogen shortage, when generally a considerable decrease was noticed in the range of genotypic variation in grain quality. CONCLUSIONS: The substitution lines, particularly those with DIC-6B and DIC-6A and to a lesser extent DIC-1A and DIC-2A, were distinguished by advantageous grain quality traits, mixing properties and dough functionality and appear to be the most promising sources of innovative genes for wheat breeding. (c) 2016 Society of Chemical Industry. PMID- 27558294 TI - Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination. AB - Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID- 27558296 TI - Development of Potent and Metabolically Stable APJ Ligands with High Therapeutic Potential. AB - The apelin ligand receptor system is an important target to develop treatment strategies for cardiovascular diseases. Although apelin exhibits strong inotropic effects, its pharmaceutical application is limited because no agonist with suitable properties is available. On the one hand, peptide ligands are too instable, and on the other hand, small-molecule agonists show only low potency. This study describes the development of apelin (APJ) receptor agonists with not only high activity but also metabolic stability. Several strategies including capping of termini, insertion of unnatural amino acids, cyclization, and lipidation were analyzed. Peptide activity was tested using a Ca2+ -mobilization assay and the degradation of selected analogues was analyzed in rat plasma. The best results were obtained by N-terminal lipidation of a 13-mer apelin derivative. This analogue displayed a half-life of 29 h in rat plasma, compared with 0.025 h for the wild-type peptide. Furthermore, in vivo pharmacokinetics revealed a clearance of 0.049 L h-1 kg-1 and a half-life of 0.36 h. In summary, amino acid substitution and fatty acid modification resulted in a potent and 1000 fold more stable peptide that exhibits high pharmaceutical potential. PMID- 27558298 TI - The mitochondria target drug avocatin B synergizes with induction chemotherapeutics to induce leukemia cell death. PMID- 27558297 TI - Depression and genetic causal attribution of epilepsy in multiplex epilepsy families. AB - OBJECTIVES: Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients' psychological responses and coping strategies, but little is known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that among members of families containing multiple individuals with epilepsy, depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause. METHODS: A self-administered survey was completed by 417 individuals in 104 families averaging 4 individuals with epilepsy per family. Current depression was measured with the Patient Health Questionnaire. Genetic causal attribution was assessed by three questions addressing the following: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual's epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. RESULTS: Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biologic relatives without epilepsy, and 3.9% in 51 individuals married into the families. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biologic relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p = 0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. SIGNIFICANCE: Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in families containing multiple affected individuals. This association should be considered when addressing mental health issues in such families. PMID- 27558299 TI - Conversation breakdowns in the audiology clinic: the importance of mutual gaze. AB - BACKGROUND: Conversational breakdowns are a persistent concern for older adults with hearing impairment (HI). Previous studies in experimental settings have investigated potential causes of breakdowns in conversations with a person with HI, and effective strategies for repairing these breakdowns. However, little research has explored the causes of hearing-related communication breakdowns, and their repairs, in extended, naturally occurring conversations in a healthcare setting. AIMS: To analyse systematically instances of clients' initiations of repair within video-recorded initial audiology appointments, and to examine the interactional environment in which they occurred. METHODS & PROCEDURES: Participants included 26 audiologists and their older adult clients (aged 55+ years). Companions were present in 17 of the 63 appointments. Conversation analysis (CA) was used to examine the video-recorded audiology appointments with older adults with HI. The corpus was systematically analysed for all instances of 'other-initiated repair' by clients (initiation of repair targeting the prior speakers' turn). A collection of 51 instances of other-initiated repair were identified. These instances were analysed in detail for: (1) the interactional environment in which they occurred; (2) the strategy by which the client initiated repair; and (3) the strategies used by the audiologist to repair the communication breakdown. OUTCOMES & RESULTS: In 76% (n = 39) of the 51 cases of other-initiated repair from the client, there was a lack of mutual gaze between participants (i.e., either the audiologist or the client were looking away or facing in another direction during the prior turn). More specifically, many of these instances occurred when the audiologist was speaking to the client while multitasking. Audiologists used multiple-repair strategies in their responsive turn in an attempt to repair the communication breakdown efficiently. CONCLUSIONS & IMPLICATIONS: These findings, from extended, naturally occurring conversations with older adults with HI in clinic settings, highlight the importance of face-to face communication even in quiet one-to-one settings. Clinicians should remain aware of their movements and gaze when speaking to clients during appointments. The findings also provide further support for the importance of communication programs in hearing rehabilitation. PMID- 27558300 TI - Diet-induced obese mice exhibit altered immune responses to acute lung injury induced by Escherichia coli. AB - OBJECTIVE: Obesity has been associated with impaired immunity and increased susceptibility to bacterial infection. It also exerts protective effects against mortality secondary to acute lung injury. The effects of obesity on immune responses to acute lung injury induced by Escherichia coli were investigated to determine if the above-mentioned differences in its effects were related to infection severity. METHODS: Diet-induced obesity (DIO) and lean control mice received intranasal instillations of 10(9) or 10(10) CFUs of E. coli. The immune responses were examined at 0 h (uninfected), 24 h, and 96 h postinfection. RESULTS: Following infection, the DIO mice exhibited higher leukocyte, interleukin (IL)-10, IL-6, and tumor necrosis factor-alpha levels and more severe lung injury than the lean mice. Following inoculation with 10(10) CFUs of E. coli, the DIO mice exhibited higher mortality and more severe inflammation induced injury than the lean mice, but no differences in E. coli counts were noted between the two groups. However, inoculated with 10(9) CFUs of E. coli, the DIO mice exhibited smaller E. coli burdens at 24 h and 96 h after infection, as well as lower concentrations of IL-10 and tumor necrosis factor-alpha and less severe lung injury at 96 h after infection. CONCLUSIONS: The results support the emerging view that obesity may be beneficial in the setting of milder infection but detrimental in the setting of more severe infection. PMID- 27558302 TI - Erratum: Virtual Planning, Control, and Machining for a Modular-Based Automated Factory Operation in an Augmented Reality Environment. PMID- 27558301 TI - The NICE Guideline - Menopause: diagnosis and management. PMID- 27558303 TI - Novel Y-chromosome short tandem repeats in Sus scrofa and their variation in European wild boar and domestic pig populations. AB - Y-chromosome markers are important tools for studying male-specific gene flow within and between populations, hybridization patterns and kinship. However, their use in non-human mammals is often hampered by the lack of Y-specific polymorphic markers. We identified new male-specific short tandem repeats (STRs) in Sus scrofa using the available genome sequence. We selected four polymorphic loci (5-10 alleles per locus), falling in one duplicated and two single-copy regions. A total of 32 haplotypes were found by screening 211 individuals from eight wild boar populations across Europe and five domestic pig populations. European wild boar were characterized by significantly higher levels of haplotype diversity compared to European domestic pigs (HD = 0.904 +/- 0.011 and HD = 0.491 +/- 0.077 respectively). Relationships among STR haplotypes were investigated by combining them with single nucleotide polymorphisms at two linked genes (AMELY and UTY) in a network analysis. A differentiation between wild and domestic populations was observed (FST = 0.229), with commercial breeds sharing no Y haplotype with the sampled wild boar. Similarly, a certain degree of geographic differentiation was observed across Europe, with a number of local private haplotypes and high diversity in northern populations. The described Y chromosome markers can be useful to track male inheritance and gene flow in wild and domestic populations, promising to provide insights into evolutionary and population genetics in Sus scrofa. PMID- 27558305 TI - 2nd Federation of Neurogastroenterology and Motility Meeting, 25-28 August 2016, Hyatt Regency San Francisco, San Francisco, California, USA. PMID- 27558304 TI - Inhibition of CD8+ T cells and elimination of myeloid cells by CD4+ Foxp3- T regulatory type 1 cells in acute respiratory distress syndrome. AB - Acute lung injury and acute respiratory distress syndrome (ARDS) are caused by rapid-onset bilateral pulmonary inflammation. We therefore investigated the potential role of interleukin (IL)-10+ CD4+ Tr1 cells, a regulatory T cell subset with previously identified immunosuppressive functions, in ARDS patients. We first showed that circulating Tr1 cells were upregulated in active and resolved ARDS patients compared to healthy controls and pneumonia patient controls. A significant fraction of these Tr1 cells expressed granzyme B and perforin, while most Tr1 cells did not express interferon gamma (IFN-gamma), IL-4, IL-17 or FOXP3, suggesting that the effector functions of these Tr1 cells were primarily mediated by IL-10, granzyme B, and perforin. Indeed, Tr1 cells effectively suppressed CD8+ T cell IFN-gamma production and induced lysis of monocytes and dendritic cells in vitro. The elimination of myeloid antigen-presenting cells depended on granzyme B production. We also discovered that Tr1 cells could be identified in the bronchoalveolar lavage fluid collected from ARDS patients. All these results suggested that Tr1 cells possessed the capacity to downregulate inflammation in ARDS. In support of this, we found that ARDS patients who resolved the inflammation and survived the syndrome contained significantly higher levels of Tr1 cells than ARDS patients who succumbed to the syndrome. Overall, this report added a novel piece of evidence that ARDS could be intervened by regulatory T cell-mediated suppressive mechanisms. PMID- 27558306 TI - Patient and family empowerment as agents of ambulatory care safety and quality. PMID- 27558307 TI - Incident reporting must result in local action. PMID- 27558308 TI - Rapid Synthesis of Aryl Fluorides in Continuous Flow through the Balz-Schiemann Reaction. AB - The Balz-Schiemann reaction remains a highly utilized means for preparing aryl fluorides from anilines. However, the limitations associated with handling aryl diazonium salts often hinder both the substrate scope and scalability of this reaction. To address this, a new continuous flow protocol was developed that eliminates the need to isolate the aryl diazonium salts. The new process has enabled the fluorination of an array of aryl and heteroaryl amines. PMID- 27558309 TI - Atrial Fibrillation is Strongly Associated With the Neutrophil to Lymphocyte Ratio in Acute Ischemic Stroke Patients: A Retrospective Study. AB - BACKGROUND: No study has investigated the relationship between hospital-admission neutrophil and lymphocyte ratio (NLR) and various stroke risk factors. We sought to determine which stroke risk factor could be the most appropriate predictor of NLR in acute ischemic stroke. METHODS: We collected data on various stroke risk factors and National Institutes of Health Stroke Scale (NIHSS) score in 1,053 acute ischemic stroke patients. The regression analysis was adjusted for confounding factors such as stroke risk factors. RESULTS: There was a trend of increased NLR with a rise in alcohol consumption, the prevalence of hypertension, cardioembolism (CE) etiology, the NIHSS scores in men and the prevalence of atrial fibrillation, other heart diseases, CE and small vessel occlusion etiology and the NIHSS scores in women. Multiple linear regression analyses, adjusted for confounding factors, showed that the atrial fibrillation and NIHSS scores in men and atrial fibrillation, diabetes mellitus as well as NIHSS scores in women had a significant positive association with NLR. However, a negative association was showed for body mass index (BMI). CONCLUSION: We confirmed that the atrial fibrillation can be a predictor of high NLR in acute stroke patients, and diabetes mellitus as well as low BMI could be a predictor of high NLR in female acute ischemic stroke patients. PMID- 27558310 TI - Growth Factor Dose Tuning for Bone Progenitor Cell Proliferation and Differentiation on Resorbable Poly(propylene fumarate) Scaffolds. AB - One approach to the development of an artificial graft material could rely on uniform coverage of a resorbable biomaterial with bone extracellular matrix (ECM). To achieve this on the surface of poly(propylene fumarate) (PPF) scaffolds, we selected a growth factor regime of basic fibroblast growth factor (FGF-2) (5 ng/mL), platelet-derived growth factor (PDGF-BB) (40 ng/mL), and epidermal growth factor (EGF) (20 ng/mL) to stimulate proliferation of bone marrow-derived human mesenchymal stem cells (BM-hMSCs). Bone morphogenetic protein (BMP) 4 (50 ng/mL), 6 (50 ng/mL), and 7 (27 ng/mL) in the presence of the following osteogenic substances: dexamethasone (10(-7) M), beta-glycerophosphate (10 mM), and ascorbic acid (50 MUg/mL) were chosen to induce differentiation of BM-hMSCs into ECM-secreting osteoblasts. These growth factors were also studied at 10* concentration to determine dose effect. Proliferation was analyzed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, scanning electron microscopy (SEM), and toluidine blue staining, whereas differentiation was analyzed through alizarin red S staining and assay, alkaline phosphatase (ALP) staining and assay, and SEM. The proliferation study suggests that a combination of EGF, PDGF-BB, and FGF-2 growth factors at optimal concentration over a period of 1 week exhibits significantly (p = 0.001) higher number of cells (116,024 +/- 5165) than these cytokines without EGF (91,706 +/- 11,965). Increasing the dosage does not show any significant effect. The BM-hMSC differentiation study results show that ALP enzyme production and mineral deposition increase from day 14 to day 21 in all groups containing BMPs and osteogenic medium. However, mineralization is significantly higher in the BMP-7 group. Furthermore, the feasibility of translating the results from two dimensional thin films to three dimensional-printed PPF scaffolds was determined through uniform initial seeding and spreading of BM-hMSCs. Therefore, we have determined the optimum dose of growth factors for proliferation and differentiation of BM-hMSCs on the surface of PPF scaffolds, which can be used to produce ECM-coated implants for the treatment of bone defects. PMID- 27558311 TI - Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: A population-based study using competing risks. AB - AIM: We examined how sociodemographic, clinical and area-level factors are related to short-term prostate cancer mortality versus mortality from other causes, a crucial distinction for this disease that disproportionately affects men older than 60 years. METHODS: We applied competing risk survival models to administrative data from the Queensland Cancer Registry (Australia) for men diagnosed with prostate cancer between January 2005 and July 2007, including stratification by Gleason score. RESULTS: The men (n = 7393) in the study cohort had a median follow-up of 5 years 3 months. After adjustment, remoteness and area level disadvantage were not significantly associated with prostate cancer mortality. However, area-level disadvantage had a significant negative relationship with hazard of death from a cause other than prostate cancer within 7 years; compared with those living in the most advantaged areas, the likelihood of mortality was higher for those in the most disadvantaged (subhazard ratio [SHR] = 1.39; 95% CI, 1.01-1.90; P = 0.041), disadvantaged (SHR = 1.51; 95% CI, 1.14-2.00; P = 0.004), middle (SHR = 1.34; 95% CI, 1.02-1.75; P = 0.034) and advantaged areas (SHR = 1.44; 95% CI, 1.09-1.89; P = 0.009). Those with Gleason score of 7 and higher had a lower hazard of prostate cancer mortality if they were living with a partner, whereas those with lower Gleason scores and living a partner had lower hazards of other-cause mortality. CONCLUSIONS: Understanding why men living in more disadvantaged areas have higher risk of non-prostate cancer mortality should be a priority. PMID- 27558313 TI - The International Classification of Functioning framework in Zika-related disabilities. PMID- 27558312 TI - Yu Ping Feng San reverses cisplatin-induced multi-drug resistance in lung cancer cells via regulating drug transporters and p62/TRAF6 signalling. AB - Yu Ping Feng San (YPFS), an ancient Chinese herbal decoction composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, has been used in the clinic for treating immune deficiency. In cancer therapy, YPFS is being combined with chemotherapy drugs to achieve improved efficacy; however, scientific evidence to illustrate this combination effect is lacking. The present study aims to demonstrate the anti-drug resistance of YPFS in cisplatin (DDP) resistant non-small cell lung cancer cells (A549/DDP). The application of YPFS exhibited a synergistic enhancement of DDP-induced cytotoxicity as well as of the apoptotic signalling molecules. DDP-induced expression of the multi-drug resistance efflux transporters was markedly reduced in the presence of YPFS, resulting in a higher intracellular concentration of DDP. In addition, the application of YPFS increased DDP-induced ROS accumulation and MMP depletion, decreased p62/TRAF6 signalling in DDP-treated A549/DDP cells. The co-treatment of DDP and YPFS in tumour-bearing mice reduced the tumour size robustly (by more than 80%), which was much better than the effect of DDP alone. These results indicate that YPFS can notably improve the DDP-suppressed cancer effect, which may be a consequence of the elevation of intracellular DDP via the drug transporters as well as the down regulation of p62/TRAF6 signalling. PMID- 27558314 TI - Impaired utilization of membrane potential by complex II-energized mitochondria of obese, diabetic mice assessed using ADP recycling methodology. AB - Recently, we used an ADP recycling approach to examine mouse skeletal muscle (SkM) mitochondrial function over respiratory states intermittent between state 3 and 4. We showed that respiration energized at complex II by succinate, in the presence of rotenone to block complex I, progressively increased with incremental additions of ADP. However, in the absence of rotenone, respiration peaked at low [ADP] but then dropped markedly as [ADP] was further increased. Here, we tested the hypothesis that these respiratory dynamics would differ between mitochondria of mice fed high fat (HF) and treated with a low dose of streptozotocin to mimic Type 2 diabetes and mitochondria from controls. We found that respiration and ATP production on succinate alone for both control and diabetic mice increased to a maximum at low [ADP] but dropped markedly as [ADP] was incrementally increased. However, peak respiration by the diabetic mitochondria required a higher [ADP] (right shift in the curve of O2 flux vs. [ADP]). ATP production by diabetic mitochondria respiring on succinate alone was significantly less than controls, whereas membrane potential trended higher, indicating that utilization of potential for oxidative phosphorylation was impaired. The rightward shift in the curve of O2 flux versus [ADP] is likely a consequence of these changes in ATP production and potential. In summary, using an ADP recycling approach, we demonstrated that ATP production by SkM mitochondria of HF/streptozotocin diabetic mice energized by succinate is impaired due to decreased utilization of DeltaPsi and that more ADP is required for peak O2 flux. PMID- 27558315 TI - Antilipolytic and antilipogenic effects of the CPT-1b inhibitor oxfenicine in the white adipose tissue of rats. AB - Oxfenicine is a carnitine-palmitoyl transferase 1b (CPT-1b)-specific inhibitor that has been shown to improve whole body insulin sensitivity while suppressing fatty acid (FA) oxidation and increasing circulating FA. Because the white adipose tissue (WAT) is an organ that stores and releases FAs, this study investigated whether oxfenicine-induced inhibition of FA oxidation affected adiposity and WAT metabolism in rats fed either low (LF) or high-fat (HF) diets. Following 8 wk of dietary intervention, male Sprague-Dawley rats were given a daily intraperitoneal injection of oxfenicine (150 mg/kg body wt) or vehicle (PBS) for 3 wk. Oxfenicine treatment reduced whole body fat oxidation, body weight, and adiposity, and improved insulin sensitivity in HF-fed rats. All of these effects occurred without alterations in food intake, energy expenditure, and ambulatory activity. In vivo oxfenicine treatment reduced FA oxidation and lipolysis in subcutaneous inguinal (SC Ing) adipocytes, whereas glucose incorporation into lipids (lipogenesis) was significantly reduced in both SC Ing and epididymal (Epid) adipocytes. In summary, our results show that oxfenicine induced inhibition of CPT-1b markedly affects WAT metabolism, leading to reduced adiposity through a mechanism that involves reduced lipogenesis in the SC Ing and Epid fat depots of rats. PMID- 27558318 TI - Atrial fibrillation and stroke: risk factors, anticoagulation, and left atrial appendage occluders. PMID- 27558316 TI - Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice. AB - Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry and computational methods to measure thousands of metabolites inclusive of most metabolic pathways. We used HRM to identify metabolic pathways and clusters of association related to inflammatory cytokines in lungs of mice with H1N1 influenza virus infection. Infected mice showed progressive weight loss, decreased lung function, and severe lung inflammation with elevated cytokines [interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma] and increased oxidative stress via cysteine oxidation. HRM showed prominent effects of influenza virus infection on tryptophan and other amino acids, and widespread effects on pathways including purines, pyrimidines, fatty acids, and glycerophospholipids. A metabolome-wide association study (MWAS) of the aforementioned inflammatory cytokines was used to determine the relationship of metabolic responses to inflammation during infection. This cytokine-MWAS (cMWAS) showed that metabolic associations consisted of distinct and shared clusters of 396 metabolites highly correlated with inflammatory cytokines. Strong negative associations of selected glycosphingolipid, linoleate, and tryptophan metabolites with IFN-gamma contrasted strong positive associations of glycosphingolipid and bile acid metabolites with IL-1beta, TNF-alpha, and IL 10. Anti-inflammatory cytokine IL-10 had strong positive associations with vitamin D, purine, and vitamin E metabolism. The detailed metabolic interactions with cytokines indicate that targeted metabolic interventions may be useful during life-threatening crises related to severe acute infection and inflammation. PMID- 27558317 TI - Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy. AB - Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired beta-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor alpha, beta-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging. PMID- 27558319 TI - Early on the scene in the field of cardiac electrophysiology. PMID- 27558320 TI - Ruth Amstein PhD: an industrious educator at the helm of Zurich Heart House. PMID- 27558321 TI - STEMI in India. PMID- 27558322 TI - Surgical Ligation for Patent Ductus Arteriosus in Extremely Premature Infants: Strategy to Reduce their Risk of Neurodevelopmental Impairment. AB - Surgical ligation for patent ductus arteriosus (PDA) in extremely low birth weight infants (ELBWIs) has been shown a possible association with neurodevelopmental impairment (NDI) because of its invasiveness. However, we have undergone surgical ligation for ELBWIs immediately after cyclooxygenase inhibitor failed to close a hemodynamically significant PDA (hsPDA) to maintain proper systemic circulation. We aimed to determine the effect of surgical ligation for hsPDA on NDI in ELBWIs. In enrolled 71 ELBWIs, the clinical parameters, including the developmental quotient (DQ), were collected and compared among three groups that were divided by closure mode: spontaneous closure (n = 11), cyclooxygenase inhibitor therapy (n = 37) and surgical ligation (n = 23). No significant differences in DQ at the age of 36 months among the three groups were found: Median (interquartile range): 92.0 (31.0), 89.0 (22.0) and 92.0 (24.5), respectively. In a comparison between groups of DQ < 70 (n = 15) and DQ >= 70 (n = 56), a significant difference was found in the parameters related to prematurity (p < 0.05 for each): gestational age [23.9 (1.70) vs. 25.4 (2.50) weeks], birth weight [595 (183) vs. 714 (192) g], Apgar score < 5 (1 min) (67% vs. 36%), and laser photocoagulation for retinopathy of prematurity (73% vs. 43%), but there was no significant association with hsPDA. Therefore, we propose that surgical ligation for hsPDA in ELBWIs should be immediately carried out for preventing future neurodevelopmental deterioration if the cyclooxygenase inhibitor failed to close hsPDA. PMID- 27558323 TI - Building the repertoire of measures of walking in Rett syndrome. AB - BACKGROUND: The repertoire of measures of walking in Rett syndrome is limited. This study aimed to determine measurement properties of a modified two-minute walk test (2MWT) and a modified Rett syndrome-specific functional mobility scale (FMS-RS) in Rett syndrome. METHODS: Forty-two girls and women with Rett syndrome (median 18.4 years, range 2.4-60.9 years) were assessed for clinical severity, gross motor skills, and mobility. To measure walking capacity, 27 of this group completed a 2MWT twice on two different assessment days. To assess walking performance, the FMS-RS was administered to the total sample of parents (n = 42) on two occasions approximately one week apart. RESULTS: There were negative correlations between clinical severity and 2MWT (r = -0.48) and FMS-RS (r = -0.60 0.66). There were positive correlations between gross motor skills and mobility and 2MWT (r = 0.51, 0.43) and FMS-RS (r = 0.71-0.93, 0.74-0.94), respectively. Test-retest reliability for the 2MWT was good with high intraday and interday correlations (ICC = 0.86-0.98). For the 2MWT, the standard error of measurement was 13.8 m and we would be 95% confident that changes greater than 38 m would be greater than within subject error. There was good test-retest reliability for all three distances on the FMS-RS (ICC = 0.94-0.99). CONCLUSIONS: Walking capacity as measured by the 2MWT showed expected but limited relationships with measures of different constructs, providing some support for concurrent validity. Walking performance as measured with the FMS-RS was more strongly consistent with other clinical measures supporting its concurrent validity. Test-retest reliability was good for both the FMS-RS and the 2MWT. Therefore, these measures have the potential to be used in clinical practice and research. Implications for Rehabilitation Walking is one of the commonest daily physical activities in ambulant girls and women with RTT. Comprehensive knowledge about the walking abilities in this population is limited. Evidence of validity and test-retest reliability have been demonstrated for the modified two-minute walk test (2MWT) and the Rett syndrome-specific functional mobility scale (FMS-RS). The 2MWT and FMS-RS offer detailed information of the capacity and performance of walking, respectively, in girls and women with RTT. PMID- 27558325 TI - Granulopoiesis and granules of human neutrophils. AB - Granules are essential for the ability of neutrophils to fulfill their role in innate immunity. Granule membranes contain proteins that react to environmental cues directing neutrophils to sites of infection and initiate generation of bactericidal oxygen species. Granules are densely packed with proteins that contribute to microbial killing when liberated to the phagosome or extracellularly. Granules are, however, highly heterogeneous and are traditionally subdivided into azurophil granules, specific granules, and gelatinase granules in addition to secretory vesicles. This review will address issues pertinent to formation of granules, which is a process intimately connected to maturation of neutrophils from their precursors in the bone marrow. We further discuss possible mechanisms by which decisions are made regarding sorting of proteins to constitutive secretion or storage in granules and how degranulation of granule subsets is regulated. PMID- 27558324 TI - Neutrophils, from cradle to grave and beyond. PMID- 27558326 TI - MicroRNAs in neutrophils: potential next generation therapeutics for inflammatory ailments. AB - Neutrophils play fundamental roles in both acute and chronic inflammatory conditions, and directly contribute to the immune pathologies in both infectious and autoimmune ailments. MicroRNAs (miRs) regulate homeostasis in health and disease by fine tuning the expression of a network of genes through post transcriptional regulation. Many miRs are expressed in restricted tissues, regulated by stress and disease, and are emerging as mediators for intercellular communication. MiR profiles have been recently utilized as biomarkers for diagnosis and prognostic purposes. In addition, several miRs are in clinical development for various diseases. A short list of miRs that regulate hematopoiesis and neutrophil development is identified. Unfortunately, very limited information is available regarding how miRs regulate neutrophil migration and activation in vivo. Extensive future work is required, especially in animal models such as mice, to illustrate the pivotal and complex miR-mediated regulatory network. In addition, zebrafish, a vertebrate model organism with conserved innate immunity, potentiated by the availability of imaging and genetic tools, will provide a platform for rapid discovery and characterization of miRs that are relevant to neutrophilic inflammation. Advances in this field are expected to provide the foundation for highly selective miR-based therapy to manipulate neutrophils in infection and inflammatory disorders. PMID- 27558327 TI - Human neutrophils in the saga of cellular heterogeneity: insights and open questions. AB - Recent findings have uncovered novel fascinating aspects of the biology of neutrophils, which ultimately attribute to these cells a broader role in inflammation and immunity. One aspect that is currently under intensive investigation is the notion of neutrophil 'heterogeneity'. Studies examining neutrophils in a variety of acute and chronic inflammatory conditions report, in fact, the recovery of CD66b(+) cells displaying neutrophil-like morphology at different degrees of maturation/activation, able to exert either immunosuppressive or proinflammatory properties. These heterogeneous populations of mature and immature neutrophils are indicated with a variety of names, including 'low density neutrophils (LDNs)', 'low density granulocytes (LDGs)', 'granulocytic-myeloid derived suppressor cells (G-MDSCs)', and immunosuppressive neutrophils. However, due to the lack of discrete markers that can unequivocally allow their specific identification and isolation, the precise phenotype and function of all these presumably novel, neutrophil-like, populations have not been correctly defined yet. Aim of this article is to summarize current knowledge on the mature and immature neutrophil populations described to date, featuring immunosuppressive or proinflammatory properties, often defined as 'subsets', as well as to critically discuss unresolved issues in the field. PMID- 27558329 TI - Neutrophil swarming: an essential process of the neutrophil tissue response. AB - Neutrophil infiltration into inflamed and infected tissues is a fundamental process of the innate immune response. While neutrophil interactions with the blood vessel wall have been intensely studied over the last decades, neutrophil dynamics beyond the vasculature have for a long time remained poorly investigated. Recent intravital microscopy studies of neutrophil populations directly at the site of tissue damage or microbial invasion have changed our perspective on neutrophil responses within tissues. Swarm-like migration patterns of neutrophils, referred to as 'neutrophil swarming', have been detected in diverse tissues under conditions of sterile inflammation and infection with various pathogens, including bacteria, fungi, and parasites. Current work has begun to unravel the molecular pathways choreographing the sequential phases of highly coordinated chemotaxis followed by neutrophil accumulation and the formation of substantial neutrophil clusters. It is now clear that intercellular communication among neutrophils amplifies their recruitment in a feed-forward manner, which provides them with a level of self-organization during neutrophil swarming. This review will summarize recent developments and current concepts on neutrophil swarming, an important process of the neutrophil tissue response with a critical role in maintaining the balance between host protection and inflammation-driven tissue destruction. PMID- 27558328 TI - Transendothelial migration: unifying principles from the endothelial perspective. AB - Transendothelial migration (TEM) of polymorphonuclear leukocytes (PMN) involves a carefully orchestrated dialog of adhesion and signaling events between leukocyte and endothelial cell. This article focuses on the contribution of endothelial cells to transmigration. The initiation of TEM itself generally requires interaction of PECAM on the leukocyte with PECAM at the endothelial cell border. This is responsible for the transient elevation of cytosolic-free calcium ions in endothelium that is required for TEM and for recruitment of membrane from the lateral border recycling compartment (LBRC). TEM requires LBRC to move to the site at which TEM will take place and for VE-cadherin to move away. Targeting of the LBRC to this site likely precedes movement of VE-cadherin and may play a role in clearing VE-cadherin from the site of TEM. The process of TEM can be dissected into steps mediated by distinct pairs of PMN/endothelial interacting molecules. CD99 regulates a step at or close to the end of TEM. CD99 signals through soluble adenylyl cyclase to activate PKA to trigger ongoing targeted recycling of the LBRC. Paracellular transmigration predominates (>=90% of events) in the cremaster muscle circulation, but transcellular migration may be more important at sites such as the blood-brain barrier. Both processes involve many of the same molecules and recruitment of the LBRC. PMID- 27558332 TI - Tyrosine kinase signaling pathways in neutrophils. AB - Neutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation-induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell-surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes. In particular, Src-family and Syk tyrosine kinases couple Fc-receptors and adhesion receptors (integrins and selectins) to various neutrophil effector functions. This pathway shows surprising similarity to lymphocyte antigen receptor signaling and involves various other enzymes (e.g. PLCgamma2), exchange factors (e.g. Vav-family members) and adapter proteins (such as ITAM-containing adapters, SLP-76, and CARD9). Those mediators trigger various antimicrobial functions and play a critical role in coordinating the inflammatory response through the release of inflammatory mediators, such as chemokines and LTB4 . Interestingly, however, tyrosine kinases have a limited direct role in the migration of neutrophils to the site of inflammation. Here, we review the role of tyrosine kinase signaling pathways in neutrophils and how those pathways contribute to neutrophil activation in health and disease. PMID- 27558331 TI - Neutrophils and the inflammatory tissue microenvironment in the mucosa. AB - The interaction of neutrophils (PMNs) and epithelial cells are requisite lines of communication during mucosal inflammatory responses. Consequences of such interactions often determine endpoint organ function, and for this reason, much interest has developed around defining the constituents of the tissue microenvironment of inflammatory lesions. Physiologic in vitro and in vivo models have aided in the discovery of components that define the basic inflammatory machinery that mold the inflammatory tissue microenvironment. Here, we will review the recent literature related to the contribution of PMNs to molding of the tissue microenvironment, with an emphasis on the gastrointestinal (GI) tract. We focus on endogenous pathways for promoting tissue homeostasis and the molecular determinants of neutrophil-epithelial cell interactions during ongoing inflammation. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation. PMID- 27558333 TI - Regulation of neutrophil functions through inhibitory receptors: an emerging paradigm in health and disease. AB - Neutrophils are the most abundant subset of leukocytes and play a crucial role in the immune responses against the daily pathogen attacks faced by the host. Neutrophils exhibit several functions for fighting microbes, including the release of granules containing highly toxic molecules, the production of reactive oxygen species and inflammatory cytokines as well as NETosis. Therefore, immune responses mediated by neutrophils must be tightly regulated to protect the host from pathogen assaults without inducing detrimental inflammation and tissue damage. There is now compelling evidence showing that neutrophils express various inhibitory receptors that specifically control their functions. Some of these inhibitory receptors are contained in the membrane of granules and rapidly move to the cell surface upon neutrophil stimulation. This fast upregulation of inhibitory receptors is an efficient way to rapidly enhance inhibitory signals and increase the neutrophil activation threshold. However, because of their ability to attenuate the immune responses of neutrophils, the inhibitory receptors are attractive target for pathogens. This review discusses these various aspects with a particular emphasis on the regulation of neutrophil behavior through immunoreceptor tyrosine-based inhibition motif (ITIM)-bearing inhibitory receptors belonging to LILR and SIGLEC multi-gene families in humans and animal models. PMID- 27558330 TI - Pathobiology of neutrophil-epithelial interactions. AB - Polymorphonuclear neutrophils (PMNs) are innate immune system cells that play an essential role in eradicating invading pathogens. PMN migration to sites of infection/inflammation requires exiting the microcirculation and subsequent crossing of epithelial barriers in mucosa-lined organs such as the lungs and intestines. Although these processes usually occur without significant damage to surrounding host tissues, dysregulated/excessive PMN transmigration and resultant bystander-tissue damage are characteristic of numerous mucosal inflammatory disorders. Mechanisms controlling PMN extravasation have been well characterized, but the molecular details regarding regulation of PMN migration across mucosal epithelia are poorly understood. Given that PMN migration across mucosal epithelia is strongly correlated with disease symptoms in many inflammatory mucosal disorders, enhanced understanding of the mechanisms regulating PMN transepithelial migration should provide insights into clinically relevant tissue targeted therapies aimed at ameliorating PMN-mediated bystander-tissue damage. This review will highlight current understanding of the molecular interactions between PMNs and mucosal epithelia and the associated functional consequences. PMID- 27558334 TI - The life cycle of phagosomes: formation, maturation, and resolution. AB - Phagocytosis, the regulated uptake of large particles (>0.5 MUm in diameter), is essential for tissue homeostasis and is also an early, critical component of the innate immune response. Phagocytosis can be conceptually divided into three stages: phagosome, formation, maturation, and resolution. Each of these involves multiple reactions that require exquisite spatial and temporal orchestration. The molecular events underlying these stages are being unraveled and the current state of knowledge is briefly summarized in this article. PMID- 27558335 TI - Priming of the neutrophil respiratory burst: role in host defense and inflammation. AB - Neutrophils are the major circulating white blood cells in humans. They play an essential role in host defense against pathogens. In healthy individuals, circulating neutrophils are in a dormant state with very low efficiency of capture and arrest on the quiescent endothelium. Upon infection and subsequent release of pro-inflammatory mediators, the vascular endothelium signals to circulating neutrophils to roll, adhere, and cross the endothelial barrier. Neutrophils migrate toward the infection site along a gradient of chemo attractants, then recognize and engulf the pathogen. To kill this pathogen entrapped inside the vacuole, neutrophils produce and release high quantities of antibacterial peptides, proteases, and reactive oxygen species (ROS). The robust ROS production is also called 'the respiratory burst', and the NADPH oxidase or NOX2 is the enzyme responsible for the production of superoxide anion, leading to other ROS. In vitro, several soluble and particulate agonists induce neutrophil ROS production. This process can be enhanced by prior neutrophil treatment with 'priming' agents, which alone do not induce a respiratory burst. In this review, we will describe the priming process and discuss the beneficial role of controlled neutrophil priming in host defense and the detrimental effect of excessive neutrophil priming in inflammatory diseases. PMID- 27558337 TI - Chloride flux in phagocytes. AB - Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO) H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium-lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes. PMID- 27558338 TI - Neutral serine proteases of neutrophils. AB - Neutrophil serine proteases (NSPs) exercise tissue-degrading and microbial killing effects. The spectrum of NSP-mediated functions grows continuously, not least because of methodological progress. Sensitive and specific FRET substrates were developed to study the proteolytic activity of each NSP member. Advanced biochemical methods are beginning to characterize common and specific NSP substrates. The resulting novel information indicates that NSPs contribute not only to genuine inflammatory neutrophil functions but also to autoimmunity, metabolic conditions, and cancer. Tight regulatory mechanisms control the proteolytic potential of NSPs. However, not all NSP functions depend on their enzymatic activity. Proteinase-3 (PR3) is somewhat unique among the NSPs for PR3 functions as an autoantigen. Patients with small-vessel vasculitis develop autoantibodies to PR3 that bind their target antigens on the neutrophil surface and trigger neutrophil activation. These activated cells subsequently contribute to vascular necrosis with life-threatening multiorgan failure. This article discusses various aspects of NSP biology and highlights translational aspects with strong clinical implications. PMID- 27558339 TI - Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation. AB - Neutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed effector molecules stored in a variety of intracellular granules. Neutrophil granules contain microbicidal factors, the membrane-bound components of the respiratory burst oxidase, membrane-bound adhesion molecules, and receptors that facilitate the execution of all neutrophil functions including adhesion, transmigration, phagocytosis, degranulation, and neutrophil extracellular trap formation. The rapid mobilization of intracellular organelles is regulated by vesicular trafficking mechanisms controlled by effector molecules that include small GTPases and their interacting proteins. In this review, we focus on recent discoveries of mechanistic processes that are at center stage of the regulation of neutrophil function, highlighting the discrete and selective pathways controlled by trafficking modulators. In particular, we describe novel pathways controlled by the Rab27a effectors JFC1 and Munc13-4 in the regulation of degranulation, reactive oxygen species and neutrophil extracellular trap production, and endolysosomal signaling. Finally, we discuss the importance of understanding these molecular mechanisms in order to design novel approaches to modulate neutrophil-mediated inflammatory processes in a targeted fashion. PMID- 27558336 TI - The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase. AB - One of the most fascinating and exciting periods in my scientific career entailed dissecting the symbiotic relationship between two membrane transporters, the Nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase complex and voltage-gated proton channels (HV 1). By the time I entered this field, there had already been substantial progress toward understanding NADPH oxidase, but HV 1 were known only to a tiny handful of cognoscenti around the world. Having identified the first proton currents in mammalian cells in 1991, I needed to find a clear function for these molecules if the work was to become fundable. The then recent discoveries of Henderson, Chappell, and colleagues in 1987-1988 that led them to hypothesize interactions of both molecules during the respiratory burst of phagocytes provided an excellent opportunity. In a nutshell, both transporters function by moving electrical charge across the membrane: NADPH oxidase moves electrons and HV 1 moves protons. The consequences of electrogenic NADPH oxidase activity on both membrane potential and pH strongly self-limit this enzyme. Fortunately, both consequences specifically activate HV 1, and HV 1 activity counteracts both consequences, a kind of yin-yang relationship. Notwithstanding a decade starting in 1995 when many believed the opposite, these are two separate molecules that function independently despite their being functionally interdependent in phagocytes. The relationship between NADPH oxidase and HV 1 has become a paradigm that somewhat surprisingly has now extended well beyond the phagocyte NADPH oxidase - an industrial strength producer of reactive oxygen species (ROS) - to myriad other cells that produce orders of magnitude less ROS for signaling purposes. These cells with their seven NADPH oxidase (NOX) isoforms provide a vast realm of mechanistic obscurity that will occupy future studies for years to come. PMID- 27558342 TI - How neutrophils kill fungi. AB - Neutrophils play a critical role in the prevention of invasive fungal infections. Whereas mouse studies have demonstrated the role of various neutrophil pathogen recognition receptors (PRRs), signal transduction pathways, and cytotoxicity in the murine antifungal immune response, much less is known about the killing of fungi by human neutrophils. Recently, novel primary immunodeficiencies have been identified in patients with a susceptibility to fungal infections. These human 'knock-out' neutrophils expand our knowledge to understand the role of PRRs and signaling in human fungal killing. From the studies with these patients it is becoming clear that neutrophils employ fundamentally distinct mechanisms to kill Candida albicans or Aspergillus fumigatus. PMID- 27558340 TI - Multifaceted effects of Francisella tularensis on human neutrophil function and lifespan. AB - Francisella tularensis in an intracellular bacterial pathogen that causes a potentially lethal disease called tularemia. Studies performed nearly 100 years ago revealed that neutrophil accumulation in infected tissues correlates directly with the extent of necrotic damage during F. tularensis infection. However, the dynamics and details of bacteria-neutrophil interactions have only recently been studied in detail. Herein, we review current understanding regarding the mechanisms that recruit neutrophils to F. tularensis-infected lungs, opsonization and phagocytosis, evasion and inhibition of neutrophil defense mechanisms, as well as the ability of F. tularensis to prolong neutrophil lifespan. In addition, we discuss distinctive features of the bacterium, including its ability to act at a distance to alter overall neutrophil responsiveness to exogenous stimuli, and the evidence which suggests that macrophages and neutrophils play distinct roles in tularemia pathogenesis, such that macrophages are major vehicles for intracellular growth and dissemination, whereas neutrophils drive tissue destruction by dysregulation of the inflammatory response. PMID- 27558343 TI - Neutrophils in cancer. AB - Neutrophils play an important role in cancer. This does not only relate to the well-established prognostic value of the presence of neutrophils, either in the blood or in tumor tissue, in the context of cancer progression or for the monitoring of therapy, but also to their active role in the progression of cancer. In the current review, we describe what is known in general about the role of neutrophils in cancer. What is emerging is a complex, rather heterogeneous picture with both pro- and anti-tumorigenic roles, which apparently differs with cancer type and disease stage. Furthermore, we will discuss the well known role of neutrophils as myeloid-derived suppressor cells (MDSC), and also on the role of neutrophils as important effector cells during antibody therapy in cancer. It is clear that neutrophils contribute substantially to cancer progression in multiple ways, and this includes both direct effects on the cancer cells and indirect effect on the tumor microenvironment. While in many cases neutrophils have been shown to promote tumor progression, for instance by acting as MDSC, there are also protective effects, particularly when antibody immunotherapy is performed. A better understanding of the role of neutrophils is likely to provide opportunities for immunomodulation and for improving the treatment of cancer patients. PMID- 27558341 TI - Human neutrophils and oral microbiota: a constant tug-of-war between a harmonious and a discordant coexistence. AB - Neutrophils are a major component of the innate host response, and the outcome of the interaction between the oral microbiota and neutrophils is a key determinant of oral health status. The composition of the oral microbiome is very complex and different in health and disease. Neutrophils are constantly recruited to the oral cavity, and their protective role is highlighted in cases where their number or functional responses are impeded, resulting in different forms of periodontal disease. Periodontitis, one of the more severe and irreversible forms of periodontal disease, is a microbial-induced chronic inflammatory disease that affects the gingival tissues supporting the tooth. This chronic inflammatory disease is the result of a shift of the oral bacterial symbiotic community to a dysbiotic more complex community. Chronic inflammatory infectious diseases such as periodontitis can occur because the pathogens are able to evade or disable the innate immune system. In this review, we discuss how human neutrophils interact with both the symbiotic and the dysbiotic oral community; an understanding of which is essential to increase our knowledge of the periodontal disease process. PMID- 27558345 TI - Proliferating cell nuclear antigen in neutrophil fate. AB - The life span of a neutrophil is a tightly regulated process as extended survival is beneficial for pathogen elimination and cell death necessary to prevent cytotoxic content release from activated neutrophils at the inflammatory site. Therefore, the control between survival and death must be a dynamic process. We have previously described that proliferating cell nuclear antigen (PCNA) which is known as a nuclear protein pivotal in DNA synthesis, is a key element in controlling neutrophil survival through its association with procaspases. Contrary to the dogma which asserted that PCNA has a strictly nuclear function, in mature neutrophils, PCNA is present exclusively within the cytosol due to its nuclear export at the end of the granulocytic differentiation. More recent studies are consistent with the notion that the cytosolic scaffold of PCNA is aimed at modulating neutrophil fate rather than simply preventing death. Ultimately, targeting neutrophil survival might have important applications not just in the field of immunology and inflammation, but also in hematology and transfusion. The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle-independent functions of PCNA and should be considered as a leader of the pack. PMID- 27558344 TI - Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal. AB - Neutrophils are the first responders to infection and injury and are critical for antimicrobial host defense. Through the generation of reactive oxidants, activation of granular constituents and neutrophil extracellular traps, neutrophils target microbes and prevent their dissemination. While these pathways are beneficial in the context of trauma and infection, their off-target effects in the context of tumor are variable. Tumor-derived factors have been shown to reprogram the marrow, skewing toward the expansion of myelopoiesis. This can result in stimulation of both neutrophilic leukocytosis and the release of immature granulocytic populations that accumulate in circulation and in the tumor microenvironment. While activated neutrophils have been shown to kill tumor cells, there is growing evidence for neutrophil activation driving tumor progression and metastasis through a number of pathways, including stimulation of thrombosis and angiogenesis, stromal remodeling, and impairment of T cell dependent anti-tumor immunity. There is also growing appreciation of neutrophil heterogeneity in cancer, with distinct neutrophil populations promoting cancer control or progression. In addition to the effects of tumor on neutrophil responses, anti-neoplastic treatment, including surgery, chemotherapy, and growth factors, can influence neutrophil responses. Future directions for research are expected to result in more mechanistic knowledge of neutrophil biology in the tumor microenvironment that may be exploited as prognostic biomarkers and therapeutic targets. PMID- 27558347 TI - Membrane-bound glucocorticoid receptors on distinct nociceptive neurons as potential targets for pain control through rapid non-genomic effects. AB - Glucocorticoids were long believed to primarily function through cytosolic glucocorticoid receptor (GR) activation and subsequent classical genomic pathways. Recently, however, evidence has emerged that suggests the presence of rapid non-genomic GR-dependent signaling pathways within the brain, though their existence in spinal and peripheral nociceptive neurons remains elusive. In this paper, we aim to systemically identify GR within the spinal cord and periphery, to verify their putative membrane location and to characterize possible G protein coupling and pain modulating properties. Double immunofluorescence confocal microscopy revealed that GR predominantly localized in peripheral peptidergic and non-peptidergic nociceptive C- and Adelta-neurons and existed only marginally in myelinated mechanoreceptive and proprioreceptive neurons. Within the spinal cord, GR predominantly localized in incoming presynaptic nociceptive neurons, in pre- and postsynaptic structures of the dorsal horn, as well as in microglia. GR saturation binding revealed that these receptors are linked to the cell membrane of sensory neurons and, upon activation, they trigger membrane targeted [35S]GTPgammaS binding, indicating G protein coupling to a putative receptor. Importantly, subcutaneous dexamethasone immediately and dose-dependently attenuated acute nociceptive behavior elicited in an animal model of formalin induced pain hypersensitivity compared to naive rats. Overall, this study provides firm evidence for a novel neuronal mechanism of GR agonists that is rapid, non-genomic, dependent on membrane binding and G protein coupling, and acutely modulates nociceptive behavior, thus unraveling a yet unconsidered mechanism of pain relief. PMID- 27558346 TI - Clearance of apoptotic neutrophils and resolution of inflammation. AB - The engulfment of apoptotic cells by phagocytes, a process referred to as efferocytosis, is essential for maintenance of normal tissue homeostasis and a prerequisite for the resolution of inflammation. Neutrophils are the predominant circulating white blood cell in humans, and contain an arsenal of toxic substances that kill and degrade microbes. Neutrophils are short-lived and spontaneously die by apoptosis. This review will highlight how the engulfment of apoptotic neutrophils by human phagocytes occurs, how heterogeneity of phagocyte populations influences efferocytosis signaling, and downstream consequences of efferocytosis. The efferocytosis of apoptotic neutrophils by macrophages promotes anti-inflammatory signaling, prevents neutrophil lysis, and dampens immune responses. Given the immunomodulatory properties of efferocytosis, understanding pathways that regulate and enhance efferocytosis could be harnessed to combat infection and chronic inflammatory conditions. PMID- 27558349 TI - A nanobiosensor for the detection of arginase activity. AB - A nanobiosensor for arginase detection was designed and synthesized. It features a central dopamine-coated iron/iron oxide nanoparticle to which sulfonated cyanine 7.0 is tethered via a stable amide bond. Cyanine 5.5 is linked to the N terminal of the peptide sequence GRRRRRRRG. Arginine (R) reacts to ornithine (O) in the presence of arginase. Based on calibration with commercially obtained arginase II, the limit of detection (LOD) is picomolar. It is noteworthy that the nanobiosensor for arginase detection does not show a fluorescence increase when incubated with the enzyme NO-reductase, which also uses arginase as substrate, but is indicative of an inflammatory response by the host to cancer and infections. Arginase activity was determined in a syngeneic mouse model for aggressive breast cancer (4T1 tumors in BALB/c mice). It was found that the arginase activity is systemically enhanced, but especially pronounced in the active tumor regions. PMID- 27558350 TI - Safety of nanosuspensions in drug delivery. AB - Nanosuspension technology is currently undergoing dramatic expansion in pharmaceutical science research and development. However, most of the research efforts generally focus on formulation and potential beneficial description, while the research into potential toxicological effects and implications (i.e., in vivo safety and health effects) is lacking. This review identifies some of the key factors for studying nanosuspension safety and the potential undesired effects related to nanosuspension exposure. The key factors for discussion herein include particle characterization, preparation approach, composition, and excipients of the formulation and sterilization methods. A few comments on the primary and required safety aspects of each administration route are also reviewed. PMID- 27558348 TI - Whole-genome characterization in pedigreed non-human primates using genotyping-by sequencing (GBS) and imputation. AB - BACKGROUND: Rhesus macaques are widely used in biomedical research, but the application of genomic information in this species to better understand human disease is still in its infancy. Whole-genome sequence (WGS) data in large pedigreed macaque colonies could provide substantial experimental power for genetic discovery, but the collection of WGS data in large cohorts remains a formidable expense. Here, we describe a cost-effective approach that selects the most informative macaques in a pedigree for 30X WGS, followed by low-cost genotyping-by-sequencing (GBS) at 30X on the remaining macaques in order to generate sparse genotype data at high accuracy. Dense variants from the selected macaques with WGS data are then imputed into macaques having only sparse GBS data, resulting in dense genome-wide genotypes throughout the pedigree. RESULTS: We developed GBS for the macaque genome using a digestion with PstI, followed by sequencing of size-selected fragments at 30X coverage. From GBS sequence data collected on all individuals in a 16-member pedigree, we characterized high confidence genotypes at 22,455 single nucleotide variant (SNV) sites that were suitable for guiding imputation of dense sequence data from WGS. To characterize dense markers for imputation, we performed WGS at 30X coverage on nine of the 16 individuals, yielding 10,193,425 high-confidence SNVs. To validate the use of GBS data for facilitating imputation, we initially focused on chromosome 19 as a test case, using an optimized panel of 833 sparse, evenly-spaced markers from GBS and 5,010 dense markers from WGS. Using the method of "Genotype Imputation Given Inheritance" (GIGI), we evaluated the effects on imputation accuracy of 3 different strategies for selecting individuals for WGS, including 1) using "GIGI Pick" to select the most informative individuals, 2) using the most recent generation, or 3) using founders only. We also evaluated the effects on imputation accuracy of using a range of from 1 to 9 WGS individuals for imputation. We found that the GIGI-Pick algorithm for selection of WGS individuals outperformed common heuristic approaches, and that genotype numbers and accuracy improved very little when using >5 WGS individuals for imputation. Informed by our findings, we used 4 macaques with WGS data to impute variants at up to 7,655,491 sites spanning all 20 autosomes in the 12 remaining macaques, based on their GBS genotypes at only 17,158 loci. Using a strict confidence threshold, we imputed an average of 3,680,238 variants per individual at >99 % accuracy, or an average 4,458,883 variants per individual at a more relaxed threshold, yielding >97 % accuracy. CONCLUSIONS: We conclude that an optimal tradeoff between genotype accuracy, number of imputed genotypes, and overall cost exists at the ratio of one individual selected for WGS using the GIGI-Pick algorithm, per 3-5 relatives selected for GBS. This approach makes feasible the collection of accurate, dense genome-wide sequence data in large pedigreed macaque cohorts without the need for more expensive WGS data on all individuals. PMID- 27558351 TI - A novel method for dengue virus detection and antibody screening using a graphene polymer based electrochemical biosensor. AB - Dengue fever is a major disease that kills many people in the developing world every year. During early infection, a patient displays a high temperature without other signs. After this stage, and without proper treatment, serious damage to internal organs can happen, which occasionally leads to death. A rapid technique for the early detection of dengue virus (DENV) could reduce the number of fatalities. This study presents a new technique for the detection, classification and antibody screening of DENV based on electrochemical impedance spectroscopy (EIS). We found that the charge transfer resistance (Rct) of a gold electrode coated with graphene oxide reinforced polymer was influenced by virus type and quantity exposed on the surface. Molecular recognition capability established during the GO-polymer composite preparation was used to explain this observation. The linear dependence of Rct versus virus concentrations ranged from 1 to 2*103pfu/mL DENV with a 0.12 pfu/mL detection limit. PMID- 27558353 TI - Cationic amphiphile in phospholipid bilayer or oil-water interface of nanocarriers affects planktonic and biofilm bacteria killing. AB - A cationic amphiphile, soyaethyl morpholinium ethosulfate (SME), immobilized in liposomes or nanoemulsions, was prepared in an attempt to compare the antibacterial activity between SME intercalated in the phospholipid bilayer and oil-water interface. Before antibacterial assessment, the size of the liposomes and nanoemulsions was respectively recorded as 75 and 214 nm. The data of minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) and live/dead cell count demonstrated a superior antimicrobial activity of nanoemulsions compared to liposomes against Staphylococcus aureus, methicillin resistant S. aureus (MRSA), and Staphylococcus epidermidis. Nanoemulsion incubation reduced biofilm thickness by 2.4-fold, whereas liposomes showed a 1.6 fold decrease in thickness. SME insertion in the oil-water phase was found to induce bacterial membrane disruption. SME nanosystems were nontoxic to keratinocytes. In vivo topical application of the cationic nanosystems reduced skin infection, MRSA load, and inflammation in mice. The deteriorated skin barrier function evoked by MRSA was recovered by nanoemulsion treatment. PMID- 27558352 TI - Characterization of alendronic- and undecylenic acid coated magnetic nanoparticles for the targeted delivery of rosiglitazone to subcutaneous adipose tissue. AB - Obesity is a state of positive energy balance where excess white adipose tissue accumulates to the detriment of metabolic health. Improving adipocyte function with systemic administration of thiazolidinediones (TZDs) improves metabolic outcomes in obesity, however TZD use is limited clinically due to undesirable side effects. Here we evaluate magnetic nanoparticles (MNPs) as a tool to target rosiglitazone (Rosi) specifically to adipose tissue. Results show Rosi can be adsorbed to MNPs (Rosi-MNPs) with hydrophobic coatings for which we present binding and release kinetics. Rosi adsorbed to MNPs retained the ability to induce PPARgamma target gene expression in cells. Biodistribution analysis of radiolabeled Rosi-MNPs revealed a fat-implanted magnet significantly enhanced localization of Rosi to the targeted adipose tissue when administered by subcutaneous injection to obese mice. We propose MNPs for targeted delivery of anti-diabetic agents to superficially located subcutaneous adipose tissue. PMID- 27558354 TI - Mechanically tuned nanocomposite coating on titanium metal with integrated properties of biofilm inhibition, cell proliferation, and sustained drug delivery. AB - The clinical success of coated implants in executing biological functions inclusive of sustainable drug release and long term antibacterial activity without antibiotics is critical. To this aim, a nanohybrid of silver nanoparticles (AgNPs) cored in polyvinyl alcohol nanocapsules (Ag-PVA NCs) embedded in chitosan (CS) matrix loaded with anti-inflammatory drug naproxen was prepared. The synthesized nanohybrids that were subjected to coatings on (3 aminopropyl)triethoxysilane (APTES) treated titanium (Ti) metal exhibited dual role of excellent inhibition on biofilm formation and sustained drug release. These dual characteristics are achieved mainly based on intrinsic antibacterial property of AgNPs and differential entrapment of drug in PVA polymeric shell of AgNPs and CS matrix. The coatings also demonstrated enhanced mechanical properties with increasing inorganic filler and stress shielding on Ti metal. The biocompatibility tests involving adhesion, proliferation and differentiation of osteoblast cells demonstrated the efficacy of Ag-PVA NCs embedded in CS matrix as a suitable coating material for orthopedic applications. PMID- 27558355 TI - Prevalence and risk factors for medication reconciliation errors during hospital admission in elderly patients. AB - Background Care transitions are risk points for medication discrepancies, especially in the elderly. Objective This study was undertaken to assess prevalence and describe medication reconciliation errors during admission in elderly patients and to analyze associated risk factors. We also evaluate the effect of these errors on the length of hospital stay. Setting General surgery, orthopedics, internal medicines and infectious diseases departments of a 1070-bed Spanish teaching hospital. Method This is a prospective observational study. Patients >65 years and taking >=5 medications were randomly selected from those admitted to hospital. The pharmacist obtained the best possible medication history based on medical records, medical notes from patients' previous admissions to hospital, "brown bag" review, community care prescriptions, and comprehensive patient interviews. It was compared to current inpatient prescription to detect unintentional discrepancies (discrepancy with no apparent clinical explanation), which were reported to the physician. When the physician accepted the discrepancy by changing the medication order, it was recorded as a medication reconciliation error and classified by type of error. Several variables were analyzed as possible risk/protective factors. Main outcome measure Is prevalence of medication reconciliation errors at admission. Results Reconciliation was performed on 206 patients. Medication reconciliation errors occurred in 49.5 % (102/206) of patients. 1996 medications were recorded, and 359 had unintentional discrepancies (56.0 % (201/359) medication reconciliation errors). The most common was omission (65.1 %). Identified risk factors were as follows: physician experience, number of pre-admission prescribed medications, and previous surgeries. Computerized order entry system was a protective factor. Conclusion Medication reconciliation errors occur in almost half of the elderly patients at admission, especially omissions. Risk factors were a larger number of previous medications, less physician years of experience, and more previous surgeries. Having a computerized order entry system in the hospital protected against some errors. PMID- 27558356 TI - In-syringe dispersive micro-solid phase extraction using carbon fibres for the determination of chlorophenols in human urine by gas chromatography/mass spectrometry. AB - In this article, carbon fibres (CFs) are presented as sorbent material for the dispersive micro-solid phase extraction of twelve chlorophenols from urine samples. CFs are synthesized by a reagentless and green procedure consisting of heating raw cotton, a natural precursor, at high temperature (400 degrees C) in an inert atmosphere (Ar) during 2h. The resulting fibres, which present good water dispersibility, are finally loaded on an in-syringe device. This device, which integrates the extraction and final elution of the analytes, is disposable and it is adapted to process low sample volumes. Working at the optimum conditions, the extraction procedure in combination with gas chromatography/mass spectrometry allows the determination of the analytes in urine at the low MUg/L range. In fact, the limits of quantification (LOQs) of the analytes were in the interval from 1MUg/L to 2.5MUg/L with precision values, expressed as relative standard deviations (RSD), better than 13%. Relative recovery values, ranging from 74.5% to 113%, demonstrate the applicability of the proposed method. PMID- 27558357 TI - Recent advances on the use of cyclodextrins in the chiral analysis of drugs by capillary electrophoresis. AB - The most recent advances on the use of cyclodextrins as chiral selectors in capillary electrophoresis for the enantioseparation of drugs are reviewed in this article. The types of cyclodextrins employed and the resolutions achieved are discussed. The use of dual chiral systems, modified capillaries, non-aqueous media or microfluidic devices is also included and the mechanisms for enantioseparation of drugs and the inversion of the enantiomer migration order are studied. The most relevant applications developed to carry out the quantitation of chiral drugs, to assess the enantiomeric purity of pharmaceutical formulations, to study their metabolism or to achieve criminalistic or forensic investigations are described. Articles published in the last six years (period from 2010 to 2015) are considered. PMID- 27558358 TI - Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development. AB - A chiral method using capillary electrophoresis was developed for the separation of the four stereoisomers of a new chiral substance currently undergoing drug development as single enantiomer. After the selection of highly sulfated beta-CD as chiral selector, an exhaustive study on the influence of several experimental variables on the resolution was performed, being the substitution degree of the CD a very decisive factor. Run time and resolutions were about 20min and higher than 2.0, respectively. The method was validated in terms of selectivity, linearity, accuracy, precision, and limits of detection and quantitation according to the requirements of the International Conference on Harmonisation for the determination of the chiral purity of a drug substance. The usefulness of the method was demonstrated in the control of stereoisomeric impurities in raw material as well as in the determination of the chiral stability of the drug in the solid state and in dosage forms used in safety assessment. Finally, the chiral method was used to investigate the possible in vivo inversion in biological samples. PMID- 27558359 TI - The quality of lactation studies including antipsychotics. AB - THE AIM OF THE STUDY: The aim of this study is to determine the quality of lactation studies that investigated antipsychotics in breast milk according to the Food and Drug Administration (FDA) and International Lactation Consultant Association (ILCA) draft guidelines. MATERIALS AND METHODS: We used the draft FDA and ILCA guidelines to review the quality of articles including antipsychotic use during breastfeeding. We used PubMed and Lactmed for the literature search. Furthermore, cross references were searched for additional studies. RESULTS: Of the 51 studies, only one olanzapine and one quetiapine study calculated the milk to plasma ratio (M:P ratio), the Absolute Infant Dose (AID), and the Relative Infant Dose (RID) correctly. In the remaining studies, at least one of the three endpoints was not determined properly. No correct endpoints were calculated in studies containing chlorpromazine, chlorprothixene, clozapine, haloperidol, sulpiride, trifluoperazine, ziprasidone, zonisamide, and zuclopenthixol. This review investigated that there was a lack of information on the sampling methods of breast milk. Furthermore, the concentrations needed for the calculations of the three endpoints were mainly based on single measurements instead of at least five measurements during one dose interval. In many studies, the RID was not calculated correctly due to the fact that the RID was not normalized by the maternal weight or an average maternal weight of 70 kg was used as a standard. CONCLUSION: Except for two studies, most studies about the safety of antipsychotic use during lactation did not meet the criteria of the draft FDA and ILCA guidelines. Further research is mandatory to assess the safety of using antipsychotics while breastfeeding. PMID- 27558360 TI - Co-administration of cyclosporine A and imatinib among patients with Philadelphia chromosome-positive leukemias in the post-transplant setting. PMID- 27558361 TI - Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation. AB - OBJECTIVE: Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF). METHODS: The research included 70 patients (the average age of 49.3 +/- 10.2 years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed. RESULTS: Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80 %, specificity-83 % and diagnostic accuracy-82 %. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50 % correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6 %, sensitivity-60 % and diagnostic accuracy-74.5 %. For only LGE specificity was 16 %, sensitivity-90 % and diagnostic accuracy-28 %. CONCLUSIONS: The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure. PMID- 27558362 TI - Cerebrospinal fluid leaks in extended endoscopic transsphenoidal surgery: covering all the angles. AB - Following extended endoscopic transsphenoidal approach (EETSA), cerebrospinal fluid (CSF) leak rate has been reported in the range of 5-50 %. Novel closure techniques, such as the nasoseptal flap and other multilayered repairs improved the outcomes significantly but took most of our focus. Little attention, however, was given to other aspects of the equation such as nasal support-to support the heavy weight of such repairs-and lumbar drains. These are important because they diminish the forces acting on both sides of the repair, hence covering all the angles. We reviewed data of 98 consecutive patients who underwent an EETSA between 1999 and 2014. We analyzed the rates of CSF leak throughout the years and with every modification added to our closure technique. Common pathologies encountered were invasive adenomas, meningiomas, chordomas, and craniopharyngiomas. CSF leak occurred overall in five patients (5.1 %). The nasoseptal flap decreased the rate of CSF leak but not significantly (P = 0.112), while placing a nasal trumpet to support our repair resulted in significant decrease in CSF leak rate (P = 0.0013). In the last 2 years of our series, when all modifications took place and all angles were covered, there was one leak in 35 cases (2.8 %). A protocol that covers all the angles by a good multilayered repair (regardless of its type and materials) while diminishing the forces acting on both sides of the repair leads to a minimal rate of CSF leak. No principle alone is effective individually. PMID- 27558363 TI - Pediatric cranial intraosseous hemangiomas: a review. AB - Hemangiomas are benign, slow-growing tumors composed of sinusoidal blood vessels. Skeletal hemangiomas are uncommon and are mostly vertebral, followed by cranial in location. Cranial hemangiomas are very rarely encountered in children. Authors report a 12-year girl who presented with a painless enlarging mass over the parietal scalp for 3 months. Imaging revealed a left parietal intraosseous lytic mass with a sunburst appearance. Enbloc removal and cranioplasty was performed, and histopathology was suggestive of hemangioma. We reviewed the literature on pediatric cranial intraosseous hemangiomas (PCIH) (age <=18 years) by searching online database. Including ours, a total of 24 cases were analyzed. Mean age was 10.2 years (range 4 months-17 years). Eight were in the first decade and 16 were in the second decade. Male:female ratio was 12:12 (1:1). A painless palpable mass was the commonest presenting feature. Parietal and frontal bones were most commonly involved. Intracranial extension was noted in cases. Mean size of the lesion was 5 cm (range 1-12 cm). Twenty-two underwent primary surgical removal while two had additional pre-operative embolization. Surgical procedures were craniectomy alone (n-3), craniectomy + cranioplasty (n-6), tumor excision + remodeling (n-3), and tumor debulking (n-2). Histopathology was cavernous type in majority of cases. Mean follow-up duration was 11.8 months (range 2-38 months). There were no recurrences. One patient died due to systemic infection. Ours is the first review exclusively on PCIH. Although rare, they need to be considered in the differential diagnosis of lytic skull lesions in children. Enbloc removal with cranioplasty is the preferred treatment in vault hemangiomas, while embolization followed by debulking would suffice in large cranial base lesions. PMID- 27558364 TI - [Thymomas]. AB - Thymomas are rare tumors but are one of the most common mediastinal neoplasms in adults and exhibit an enormous variability in histological, biological and genetic features. The morphological spectrum within a given entity is enormous and some tumors with histological patterns of more than one entity are more common than pure histological subtypes. Due to a lack of subtype-specific markers classification of thymomas often requires complex diagnostic algorithms. The refined presentation including the definition of obligatory and optional features and of diagnostic immunohistochemical profiles, is the focus of the new World Health Organization (WHO) classification of thymomas, aiming at improving diagnostic reproducibility. This review highlights novel aspects of the WHO classification of thymomas and addresses typical differential diagnostic challenges with a focus on diagnostic pitfalls. PMID- 27558366 TI - Applications of Quantum Cascade Laser Spectroscopy in the Analysis of Pharmaceutical Formulations. AB - Quantum cascade laser spectroscopy was used to quantify active pharmaceutical ingredient content in a model formulation. The analyses were conducted in non contact mode by mid-infrared diffuse reflectance. Measurements were carried out at a distance of 15 cm, covering the spectral range 1000-1600 cm(-1) Calibrations were generated by applying multivariate analysis using partial least squares models. Among the figures of merit of the proposed methodology are the high analytical sensitivity equivalent to 0.05% active pharmaceutical ingredient in the formulation, high repeatability (2.7%), high reproducibility (5.4%), and low limit of detection (1%). The relatively high power of the quantum-cascade-laser based spectroscopic system resulted in the design of detection and quantification methodologies for pharmaceutical applications with high accuracy and precision that are comparable to those of methodologies based on near-infrared spectroscopy, attenuated total reflection mid-infrared Fourier transform infrared spectroscopy, and Raman spectroscopy. PMID- 27558365 TI - Body image perception of African immigrants in Europe. AB - Nutritional disorders are now spreading worldwide both in developed and developing countries. Body image ideals and dissatisfaction have been linked to a number of poor health outcomes, including nutritional disorders. While previous studies have offered insight into weight status and body image perception of immigrants in North America, very few studies have analysed these aspects in migrants from Africa to Europe. Our review examines the effects of the migration process on beauty ideals and body dissatisfaction in African immigrants in Europe compared to residents in their own countries. The PubMed, PsycINFO and Google Scholar databases were searched for studies published from January 2000 till November 2015. Of the 730 titles identified, 26 met the inclusion criteria and were included in the present review. Among African residents, the body preferences depend on the country of residence and their socio-cultural status. Ethnic groups living in great isolation or with low incomes still have an ancestral idea of beauty, preferring a shapely body. However ethnic groups living in urban areas are moving toward Westernization of beauty ideals, preferring underweight or normal weight bodies. This review highlights that both residents and migrants are at high risk of nutritional disorders due to the adoption of Western beauty ideals. The results suggest that body dissatisfaction and BMI are increasing from Southern Africa to Europe according to a geographical gradient (described for females by Spearman's coefficient and linear regression, respectively). We emphasize the need for monitoring of the weight and psychological status of immigrants and the development of specific preventive strategies in European countries. PMID- 27558367 TI - Ethylene Glycol - Polyethylene Glycol (EG-PEG) Mixtures: Infrared Spectra Wavelet Cross-Correlation Analysis. AB - Infrared spectra were collected on mixtures of ethylene glycol (EG) and polyethylene glycol 600 (PEG600) as a function of weight fraction from pure EG to pure PEG600. In this paper, it will be shown that while the OH vibrational contribution drastically reduces its center frequency from 3450 cm-1 to 3300 cm-1 in the weight fraction range 0-25%, the displacement of the mixture spectral features of the mixtures from ideal behavior, i.e., in the absence of interaction, shows the presence of a non-ideal mixing process. Furthermore, wavelet cross-correlation analysis of the registered pairs of spectra and of the intramolecular O-H stretching contributions reveals how the addition of a small amount of pure EG to PEG600 dramatically influences the structural properties of the polymeric matrix, owing to an increase the intermolecular connectivity. In particular, the wavelet cross-correlation parameters, evaluated between each pair of the registered data as a function of weight fraction, in a linear-logarithmic plot, reveals an inflection point for a weight fraction of about 25% of EG, which confirms that, within the three-dimensional networks of hydrogen-bonded EG-PEG600 molecules, a key role is played by EG in determining an increase in the hydrogen bond network density. PMID- 27558369 TI - Seeking the "holy grail" of biomarkers to improve stroke risk prediction of clinical scores. PMID- 27558368 TI - Cancer risk in DM1 is sex-related and linked to miRNA-200/141 downregulation. AB - OBJECTIVE: Describe the incidence of cancer in a large cohort of patients with myotonic dystrophy type 1 (DM1) and to unravel the underlying molecular mechanisms. METHODS: Standardized incidence ratios (SIRs) were calculated in the Gipuzkoa DM1 cohort (1985-2013), dividing observed numbers by expected numbers for all cancers combined and stratified by sex. An estimation of the expected incidence was achieved by multiplying the age- and sex-specific incidence rates from the Basque population cancer registry by the person-years observed in the study cohort. Large-scale gene expression of peripheral blood mononuclear cell samples derived from 10 individuals with DM1 (5 men, 5 women) and 10 healthy matched controls was analyzed by the Human Gene 1.0 ST Affymetrix microarray. RESULTS: During 18,796 person-years of follow-up, corresponding to 424 patients with DM1, we observed 70 cancers in 62 patients giving a 1.81-fold risk (95% confidence interval [CI] 1.37-2.36), which was stronger in women than in men. Ovary (SIR 8.33, 95% CI 1.72-24.31) and endometrium (SIR 6.86, 95% CI 2.23-16.02) in women and thyroid (SIR 23.33, 95% CI 9.38-48.08) and brain (SIR 9.80, 95% CI 3.18-22.88) in both sexes were tumor sites with significantly higher risks in DM1. There were differences in gene expression between healthy controls and patients with DM1 and between men and women with DM1; all patients with DM1 combined and female patients with DM1 displayed significant downregulation of the microRNA (miRNA)-200c/141 tumor suppressor family. CONCLUSIONS: Oncologic risk is increased in DM1, especially in women and for gynecologic, brain, and thyroid cancer. Expression of the miRNA-200/miRNA-141 tumor suppressor family is decreased in women with DM1. PMID- 27558370 TI - AMPA receptors: Dynamics and targets of disease. PMID- 27558371 TI - Comment: Genotype-phenotype correlation with CRISPR-Cas9-: Bedside to bench. PMID- 27558373 TI - Hypertension prevention: In need of a grain of salt knowledge. PMID- 27558372 TI - NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations. AB - OBJECTIVE: To perform genotype-phenotype analysis in an infant with congenital arthrogryposis due to a de novo missense mutation in the NALCN ion channel and explore the mechanism of pathogenicity using a Caenorhabditis elegans model. METHODS: We performed whole-exome sequencing in a preterm neonate with congenital arthrogryposis and a severe life-threatening clinical course. We examined the mechanism of pathogenicity of the associated NALCN mutation by engineering the orthologous mutation into the nematode C elegans using CRISPR-Cas9. RESULTS: We identified a de novo missense mutation in NALCN, c.1768C>T, in an infant with a severe neonatal lethal form of the recently characterized CLIFAHDD syndrome (congenital contractures of the limbs and face with hypotonia and developmental delay). We report novel phenotypic features including prolonged episodes of stimulus-sensitive sustained muscular contraction associated with life threatening episodes of desaturation and autonomic instability, extending the severity of previously described phenotypes associated with mutations in NALCN. When engineered into the C elegans ortholog, this mutation results in a severe gain-of-function phenotype, with hypercontraction and uncoordinated movement. We engineered 6 additional CLIFAHDD syndrome mutations into C elegans and the mechanism of action could be divided into 2 categories: half phenocopied gain-of function mutants and half phenocopied loss-of-function mutants. CONCLUSIONS: The clinical phenotype of our patient and electrophysiologic studies show sustained muscular contraction in response to transient sensory stimuli. In C elegans, this mutation causes neuronal hyperactivity via a gain-of-function NALCN ion channel. Testing human variants of NALCN in C elegans demonstrates that CLIFAHDD can be caused by dominant loss- or gain-of-function mutations in ion channel function. PMID- 27558374 TI - Influence of sodium consumption and associated knowledge on poststroke hypertension in Uganda. AB - OBJECTIVE: We assessed 24-hour urine sodium levels as an index of dietary salt consumption and its association with dietary salt knowledge and hypertension among poststroke patients with and without a history of hypertension in Uganda. METHODS: A case-control study in which poststroke patients with a history of hypertension (cases, n = 123) were compared to poststroke patients without known hypertension (controls, n = 112). Dietary salt intake was assessed by 24-hour urine sodium, a valid measure of dietary salt consumption. Dietary salt knowledge was determined by questionnaire. The independent relationships among salt knowledge, 24-hour urine sodium, and blood pressure control were assessed using multiple regression analysis. RESULTS: High 24-hour urine sodium (>=8.5 g/d) was 2 times more prevalent among hypertensive poststroke patients than controls (p = 0.002). Patients with minimal poststroke disability who had a choice in determining their diets had higher urine sodium than their more disabled counterparts. Only 43% of the study population had basic dietary salt knowledge, 39% had adequate diet-disease-related knowledge, and 37% had procedural knowledge (report of specific steps being taken to reduce salt consumption). Dietary salt knowledge was similarly poor among cases and controls (p = 0.488) and was not related to education level (p = 0.205). CONCLUSIONS: High urine sodium and high salt-diet preferences were more frequent among poststroke hypertensive patients in Uganda than in their nonhypertensive counterparts. There was, however, no difference in dietary salt knowledge between these groups. The development of educational strategies that include salt-diet preferences may lead to better blood pressure control in this high-risk population. PMID- 27558376 TI - Acute intermittent porphyria-related leukoencephalopathy. AB - OBJECTIVE: To identify the genetic etiology of a distinct leukoencephalopathy with autosomal recessive inheritance in a single family. METHODS: We analyzed available MRIs and retrospectively reviewed clinical information and laboratory investigations. We performed whole-exome sequencing to find the causal gene variants. RESULTS: We identified 3 family members with a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons. Cerebellar atrophy was noted in advanced disease stages. Clinical features were childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. Whole-exome sequencing revealed compound heterozygous missense variants in the HMBS gene, both associated with the autosomal dominant disorder acute intermittent porphyria. Sanger sequencing of 6 healthy siblings confirmed the bi-allelic location of the variants and segregation with the disease. Patients had a slight and moderate increase in urinary and plasma porphobilinogen and 5'-aminolevulinic acid, respectively, and a 50% to 66% decrease in hydroxymethylbilane synthase enzyme activity compared to normal. CONCLUSIONS: Bi allelic HMBS variants have been reported before as cause of severe encephalopathy with early childhood fatality in acute intermittent porphyria. Our cases demonstrate childhood onset, but milder and slower disease progression in middle aged patients. With this, a novel phenotype can be added to the disease spectrum associated with bi-allelic HMBS variants: a leukoencephalopathy with early onset, slowly progressive neurologic symptomatology, and long life expectancy. PMID- 27558375 TI - MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP-parkinsonism. AB - OBJECTIVE: To identify a biomarker for predicting the appearance of vertical supranuclear gaze palsy (VSGP) in patients affected by progressive supranuclear palsy-parkinsonism (PSP-P). METHODS: Twenty-four patients with PSP-P were enrolled in the current study. Patients were clinically followed up every 6 months until the appearance of VSGP or the end of the follow-up (4 years). Participants underwent MRI at baseline and at the end of follow-up. Magnetic resonance parkinsonism index (MRPI), an imaging measure useful for diagnosing PSP, was calculated. RESULTS: Twenty-one patients with PSP-P completed follow-up, and 3 patients dropped out. Eleven of 21 patients with PSP-P developed VSGP after a mean follow-up period of 28.5 months (range 6-48 months), while the remaining 10 patients with PSP-P did not develop VSGP during the 4-year follow-up period. At baseline, patients with PSP-P who later developed VSGP had MRPI values significantly higher than those of patients not developing VSGP without overlapping values between the 2 groups. MRPI showed a higher accuracy (100%) in predicting VSGP than vertical ocular slowness (accuracy 33.3%) or postural instability with or without vertical ocular slowness (accuracy 71.4% and 42.9%, respectively). CONCLUSIONS: Our study demonstrates that MRPI accurately predicted, on an individual basis, the appearance of VSGP in patients with PSP-P, thus confirming clinical diagnosis in vivo. PMID- 27558377 TI - Report of a workshop on research gaps in the treatment of cerebral palsy. AB - Cerebral palsy (CP) is heterogeneous in etiology and manifestations, making research into relevant therapies difficult and limiting the generalizability of the results. We report here on the NIH CP symposium, where stakeholders from academic, clinical, regulatory, and advocacy backgrounds discussed the major challenges and needs for moving forward with clinical research in CP, and outlined priorities and action items. New information is constantly generated through research into pathogenesis and etiology. Clinical research and new therapeutic approaches need to keep pace, through large data registry integration and new research designs. Development of standardized data collection, increasing academic focus on CP research, and iterative approaches to treatment throughout the patients' lives, have all been identified as areas of focus. The workshop identified critical gaps and areas of focus to increase the evidence base for therapeutic approaches to determine which treatments work best for which patients in the near future. These include consolidation and optimization of databases and registries, updates to the research methodology, and better integration of resources and stakeholders. PMID- 27558378 TI - Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration. AB - OBJECTIVE: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. METHODS: We evaluate an implementation of the recent National Institute for Aging-Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. RESULTS: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. CONCLUSIONS: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population. PMID- 27558379 TI - Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study. AB - OBJECTIVE: We related a panel of inflammatory biomarkers to risk of incident ischemic stroke (IIS) in a community-dwelling sample. METHODS: Stroke-free Framingham offspring attending examination cycle 7 (1998-2001) had 15 circulating inflammatory biomarkers measured. Cox proportional hazard models were used to calculate the hazard ratios (HRs) of IIS per SD increment of each biomarker. Model 1 included age and sex. Model 2 additionally adjusted for systolic blood pressure, hypertension treatment, current smoking, diabetes, cardiovascular disease, and atrial fibrillation. The continuous net reclassification improvement was used to assess the improvement in IIS risk prediction of statistically significant biomarkers from our main analysis over traditional stroke risk factors. RESULTS: In 3,224 participants (mean age 61 +/- 9 years, 54% women), 98 experienced IIS (mean follow-up of 9.8 [+/-2.2] years). In model 1, ln-C-reactive protein (ln-CRP) (HR 1.28, 95% confidence interval [CI] 1.04-1.56), ln-tumor necrosis factor receptor 2 (ln-TNFR2) (HR 1.33, 95% CI 1.09-1.63), ln-total homocysteine (ln-tHcy) (HR 1.32, 95% CI 1.11-1.58), and vascular endothelial growth factor (VEGF) (HR 1.25, 95% CI 1.07-1.46) were associated with risk of IIS. All associations, except for ln-CRP, remained significant in model 2 (ln TNFR2: HR 1.24, 95% CI 1.02-1.51; ln-tHcy: HR 1.20, 95% CI 1.01-1.43; and VEGF: HR 1.21, 95% CI 1.04-1.42). The addition of these 4 biomarkers to the clinical Framingham Stroke Risk Profile score improved stroke risk prediction (net reclassification improvement: 0.34, 0.12-0.57; p < 0.05). CONCLUSIONS: Higher levels of 4 biomarkers-CRP, tHcy, TNFR2, and VEGF-increased risk of IIS and improved the predictive ability of the Framingham Stroke Risk Profile score. Further research is warranted to explore their role as potential therapeutic targets. PMID- 27558381 TI - Bacterial colonization of the peri-implant sulcus in dentate patients: a prospective observational study. AB - OBJECTIVES: The aim of the present study was to compare the composition of the periodontal microflora at baseline (T0) with the submucosal microflora at least 1 year after implant placement (T1) in periodontally healthy patients. MATERIAL AND METHODS: For all 169 consecutive patients that visited our clinic during 1 year, we determined their periodontal parameters, implant mucosal index, and presence of implant calculus. At T0, self-reported smoking status was recorded and subgingival and submucosal biofilm samples were obtained and analyzed for the presence and numbers of selected periodontal pathogens. All measurements were repeated at T1. RESULTS: One hundred twenty patients completed the study. Periodontal parameters were stable or had improved at T1. The total bacterial load was lower at implant sites (P < 0.05). The prevalence of Porphyromonas gingivalis was low at baseline, but at T1, detection rate and numbers were higher at implant sites compared to dentate sites. At T1, the frequency of detection of P. gingivalis (P = 0.01), Parvimonas micra (P = 0.018), and Fusobacterium nucleatum (P = 0.035) was higher in smoking patients (n = 23) than in non-smokers (n = 97). CONCLUSIONS: Colonization of the submucosal peri-implant area is similar to the composition of subgingival microbiota. Smoking has a measurable effect on the colonization of implant-associated biofilms and may select for P. gingivalis, P. micra, and F. nucleatum. CLINICAL RELEVANCE: The colonization of implants by well-known periodontal pathogens is very similar to that in normal dentition, also in a healthy cohort. Smoking status was related with the prevalence of periodontal pathogens where smokers harbored more often periodontal pathogens such as P. gingivalis, P. micra, and F. nucleatum. PMID- 27558380 TI - Cell surface-anchored syndecan-1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis. AB - Syndecan-1 (SDC1), with a variable ectodomain carrying heparan sulphate (HS) chains between different Syndecans, participates in many steps of inflammatory responses. In the process of proteolysis, the HS chains of the complete extracellular domain can be shed from the cell surface, by which they can mediate most of SDC1's function. However, the exact impact on SDC1 which anchored on the cell surface has not been clearly reported. In our study, we established the models by transfection with the cleavable resistant SDC1 mutant plasmid, in which SDC1 shedding can be suppressed during stimulation. Role of membrane SDC1 in inflammatory pathway, pro-inflammatory cytokine secretion as well as neutrophil transmigration, and how suppressing its shedding will benefit colitis were further investigated. We found that the patients suffered ulcerative colitis had high serum SDC1 levels,presented with increased levels of P65, tumour necrosis factor alpha (TNF-alpha) and IL-1beta and higher circulating neutrophils. NF kappaB pathway was activated, and secretion of TNF-alpha, interleukin-1beta (IL 1beta), IL-6 and IL-8 were increased upon lipopolysaccharide stimuli in intestinal epithelial cells. Syndecan-1, via its anchored ectodomain, significantly lessened these up-regulation extents. It also functioned in inhibiting transmigration of neutrophils by decreasing CXCL-1 secretion. Moreover, SDC1 ameliorated colitis activity and improved histological disturbances of colon in mice. Taken together, we conclude that suppression of SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation and neutrophil transmigration by inactivating key inflammatory regulators NF-kappaB, and down-regulating pro-inflammatory cytokine expressions. These indicated that compenstion and shedding suppression of cytomembrane SDC1 might be the optional therapy for intestinal inflammation. PMID- 27558382 TI - Persistence of Porphyromonas gingivalis is a negative predictor in patients with moderate to severe periodontitis after nonsurgical periodontal therapy. AB - OBJECTIVES: The aim of this study was to evaluate the quality of prediction for stable results after nonsurgical periodontal therapy by several microbiological variables of the subgingival biofilm and biomarkers of gingival crevicular fluid or oral lavage. MATERIAL AND METHODS: Forty-six individuals with moderate or severe chronic periodontitis receiving nonsurgical periodontal therapy were monitored for clinical variables, selected microorganisms, and biomarkers at baseline and 3 and 6 months thereafter. Logistic regression analysis and general linear model (GLM) were applied for analysis of variance and covariance. RESULTS: At 6 months, 20 patients showed a high response (HR) to treatment (at least 60 % of reduction of numbers of sites with PD >4 mm), whereas 26 did not (low response, LR). All clinical variables were significantly improved at 3 and 6 months within each group (p < 0.001, each compared with baseline). Modeling the impact of Porphyromonas gingivalis, Treponema denticola, and median of MMP-8 on to the response to treatment as continuous variables by GLM showed a significant influence of these variables (p = 0.045) with the strongest influence of P. gingivalis (p = 0.012) followed by T. denticola (p = 0.045) and no association with MMP-8 (p = 0.982). Samples tested positively for P. gingivalis decreased only in HR (3 months: p = 0.003; 6 months: p = 0.002). Calprotectin levels in GCF were lower in the HR group compared with the LR group at 3 months (p = 0.008) and at 6 months (p = 0.018). CONCLUSION: Persistence of P. gingivalis combined with a high GCF level of calprotectin may have a negative predictive value on response to periodontal therapy. CLINICAL RELEVANCE: Microbiological diagnostics for P. gingivalis before and 3 months after SRP may have a predictive value on response to periodontal therapy. The combination with MMP-8 in oral lavage or preferably calprotectin in GCF might give additional information. PMID- 27558383 TI - The spatial structure of chronic morbidity: evidence from UK census returns. AB - BACKGROUND: Disease prevalence models have been widely used to estimate health, lifestyle and disability characteristics for small geographical units when other data are not available. Yet, knowledge is often lacking about how to make informed decisions around the specification of such models, especially regarding spatial assumptions placed on their covariance structure. This paper is concerned with understanding processes of spatial dependency in unexplained variation in chronic morbidity. METHODS: 2011 UK census data on limiting long-term illness (LLTI) is used to look at the spatial structure in chronic morbidity across England and Wales. The variance and spatial clustering of the odds of LLTI across local authority districts (LADs) and middle layer super output areas are measured across 40 demographic cross-classifications. A series of adjacency matrices based on distance, contiguity and migration flows are tested to examine the spatial structure in LLTI. Odds are then modelled using a logistic mixed model to examine the association with district-level covariates and their predictive power. RESULTS: The odds of chronic illness are more dispersed than local age characteristics, mortality, hospitalisation rates and chance alone would suggest. Of all adjacency matrices, the three-nearest neighbour method is identified as the best fitting. Migration flows can also be used to construct spatial weights matrices which uncover non-negligible autocorrelation. Once the most important characteristics observable at the LAD-level are taken into account, substantial spatial autocorrelation remains which can be modelled explicitly to improve disease prevalence predictions. CONCLUSIONS: Systematic investigation of spatial structures and dependency is important to develop model-based estimation tools in chronic disease mapping. Spatial structures reflecting migration interactions are easy to develop and capture autocorrelation in LLTI. Patterns of spatial dependency in the geographical distribution of LLTI are not comparable across ethnic groups. Ethnic stratification of local health information is needed and there is potential to further address complexity in prevalence models by improving access to disaggregated data. PMID- 27558384 TI - Outcome of balloon kyphoplasty for the treatment of osteoporotic vertebral compression fracture in patients with rheumatoid arthritis. AB - BACKGROUND: Osteoporosis and osteoporotic fractures are widely known as complications of rheumatoid arthritis. Kyphoplasty (KP) is known as an effective treatment modality for reducing pain and correcting kyphotic deformity in osteoporotic vertebral compression fracture (OVCF). However, cutcomes of KP in rheumatoid patients are not well known. The purpose of the study was to investigate the clinical and radiological outcomes of balloon KP on OVCF in patients with rheumatoid arthritis. METHODS: A total of 23 patients (31 vertebral bodies) with rheumatoid arthritis who received KP for OVCF and could be followed up for at least 1 year were examined. For clinical outcomes, visual analogue scale (VAS) and the Korean version of the Oswestry disability index (KODI) were evaluated. For radiological outcomes, changes in anterior vertebral height and local kyphotic angle were measured, alongside cement leakage, adjacent fracture, and the recollapse of cemented vertebra. RESULTS: The anterior vertebral height was significantly restored after surgery compared with prior to surgery (p < 0.001). Cement leakage was found in 14 cases (45.1 %), and disc space leakage was prevalent (50 %), while vascular cement leakage was found in one case. Adjacent fracture was found in 3 patients (11.5 %). VAS for lumbago showed a significant decrease (p < 0.001) after surgery (VAS = 2.4) compared with that before (VAS = 8.1); it was somewhat increased after the 1-year follow-up (VAS = 2.8; p = 0.223). KODI also decreased (48.8 %) after surgery compared with before (84.6 %). However, it increased somewhat (49.9 %) after the 1-year follow-up. CONCLUSION: KP on rheumatoid arthritis patients for OVCF was effective for reducing pain in the early stage and restoring vertebral body height. Recollapse of the treated vertebral body was found relatively frequently alongside the correction loss of local kyphotic angle. PMID- 27558385 TI - Analytical modeling and feasibility study of a multi-GPU cloud-based server (MGCS) framework for non-voxel-based dose calculations. AB - PURPOSE: In this paper, a multi-GPU cloud-based server (MGCS) framework is presented for dose calculations, exploring the feasibility of remote computing power for parallelization and acceleration of computationally and time intensive radiotherapy tasks in moving toward online adaptive therapies. METHODS: An analytical model was developed to estimate theoretical MGCS performance acceleration and intelligently determine workload distribution. Numerical studies were performed with a computing setup of 14 GPUs distributed over 4 servers interconnected by a 1 Gigabits per second (Gbps) network. Inter-process communication methods were optimized to facilitate resource distribution and minimize data transfers over the server interconnect. RESULTS: The analytically predicted computation time predicted matched experimentally observations within 1 5 %. MGCS performance approached a theoretical limit of acceleration proportional to the number of GPUs utilized when computational tasks far outweighed memory operations. The MGCS implementation reproduced ground-truth dose computations with negligible differences, by distributing the work among several processes and implemented optimization strategies. CONCLUSIONS: The results showed that a cloud based computation engine was a feasible solution for enabling clinics to make use of fast dose calculations for advanced treatment planning and adaptive radiotherapy. The cloud-based system was able to exceed the performance of a local machine even for optimized calculations, and provided significant acceleration for computationally intensive tasks. Such a framework can provide access to advanced technology and computational methods to many clinics, providing an avenue for standardization across institutions without the requirements of purchasing, maintaining, and continually updating hardware. PMID- 27558386 TI - Molecular evolution of the multiple calmodulin-like cal genes in C. elegans and in nematodes. AB - Calmodulin (CaM) is a major EF hand containing intracellular calcium receptor in animals and plants; however, eukaryotes also express a number of related CaM-like proteins. We have previously characterized an embryonic phenotype of the single Caenorhabditis elegans CaM gene cmd-1, reported no visible RNAi phenotype for the four related cal-1 to cal-4 genes and started tissue-specific expression analyses of these proteins. In the present study, we analyzed evolutionary aspects of the previously reported CAL-1 to CAL-4 proteins, along with the four new CAL-5 to CAL 8 sequences retrieved from the worm database. Phylogenetic analyses suggest that all C. elegans CAL proteins arose from a CaM ancestor through repeated gene duplications, fusions and sequence divergence. The same holds, also, for the variable N-terminal extensions of the CAL-1 to CAL-4 proteins, which have evolved from the CaM-like core domain. We found 97 CAL homologs in different nematode clades and also detected two CAL-7-related sequences outside the nematodes. Moreover, the C. elegans-specific cal-6 gene, representing the most CaM-related sequence found in nematodes so far, harbours many deletions, insertions and sequence substitutions and is predicted, therefore, to be non-functional. These analyses provide an insight into a complex and dynamic origin of the multiple CAL genes in C. elegans and in nematodes and represent also a basis for further functional studies of these CaM-related sequences in nematodes. PMID- 27558387 TI - Localized oral mucous membrane pemphigoid: successful topical treatment with 1% tacrolimus solution as steroid-sparing therapy. PMID- 27558388 TI - Head injuries in youth are often linked to psychiatric disorders and disability, study finds. PMID- 27558389 TI - Auto-immune thyroid dysfunction induced by tyrosine kinase inhibitors in a patient with recurrent chordoma. AB - BACKGROUND: While hypothyroidism has frequently been reported with the use of TKIs, the thyroid-stimulating hormone (TSH) suppressing effect of TKIs is rare, except for thyroiditis. We describe a case with progressive recurrent chordoma who initially became hyperthyroid in a context of autoimmunity under sorafenib treatment and later under imatinib treatment. CASE PRESENTATION: A 57-year-old man with lumbar chordoma began daily treatment of 800 mg sorafenib. He did not have any other medication or recent iodinated-contrast exposure and his family history was negative for thyroid and autoimmune disease. There was no history of neck pain, irradiation or trauma, recent fever or viral illness. Pre-treatment TSH was normal. After 18 weeks of treatment, the patient presented hyperthyroidism with positive anti-TSH receptor antibodies. More surprisingly, Graves' disease recurred during treatment with imatinib. CONCLUSION: The fact that Graves' disease occurred after two different TKIs suggests that it could be a rare but important class effect. Anti-TSH receptor antibodies should be systematically measured when TSH decreases in order to avoid the erroneous diagnosis of transient hyperthyroidism due to thyroiditis. PMID- 27558390 TI - Nanoformulation of curcumin protects HUVEC endothelial cells against ionizing radiation and suppresses their adhesion to monocytes: potential in prevention of radiation-induced atherosclerosis. AB - OBJECTIVES: To investigated the potential of a novel dendrosomal nanoformulation of curcumin (DNC) in blocking radiation-induced changes in irradiated human umbilical vein endothelial cells (HUVECs), and their adhesion to human THP-1 monocytoid cells. RESULTS: Co60 gamma rays reduced viability, raised the expression of adhesion molecules, ICAM-1, VCAM-1 and E-selectin (mRNA and protein), augmented the adhesion of THP-1 cells to HUVECs, activated NF-kappaB binding, increased the release of pro-inflammatory cytokines (IL-6, IL-8 and MCP 1) and induced oxidative damage (reduced glutathione declined, while 8-OHdG and TBARS increased). 5 uM DNC significantly inhibited these radiation-induced changes, activated the Nrf-2 pathway, and effectively suppressed THP-1 adhesion to HUVECs, implicating p38 MAPK signaling. CONCLUSION: DNC treatment is a potential preventive method against inflammation and vascular damage from ionizing radiation. PMID- 27558391 TI - [Invasive treatment of hypertension : Update 2016]. AB - Invasive treatment methods-more specifically renal denervation and baroreceptor activator therapy-have been used for the treatment of therapy-resistant hypertension for several years now. In particular, renal denervation has aroused great interest because it was easy to perform and the first studies provided very promising results. Meanwhile, however, three randomized, blinded studies have been published, and none showed a significant benefit of renal denervation compared to a sham procedure. In addition, in several studies it was demonstrated that intensification of drug therapy, particularly with spironolactone, is at least comparable. Carotid sinus node baroreceptor activator therapy tends to be superior to renal denervation, but the probe currently used is not optimal. The first results by inserting an arteriovenous shunt between the iliac artery and vein are promising, but lack long-term safety data. Currently, all invasive treatment procedures should be performed within the framework of studies or accurate register surveys. PMID- 27558392 TI - Mars ain't the kind of place to raise your kid: ethical implications of pregnancy on missions to colonize other planets. AB - The colonization of a new planet will inevitably bring about new bioethical issues. One is the possibility of pregnancy during the mission. During the journey to the target planet or moon, and for the first couple of years before a colony has been established and the colony has been accommodated for children, a pregnancy would jeopardize the safety of the crew and the wellbeing of the child. The principal concern with a pregnancy during an interplanetary mission is that it could put the entire crew in danger. Resources such as air, food, and medical supplies will be limited and calculated to keep the crew members alive. We explore the bioethical concerns of near-future space travel. PMID- 27558393 TI - Attention Problems as a Mediator of the Relation between Executive Function and Social Problems in a Child and Adolescent Outpatient Sample. AB - Social functioning is critical for the successful navigation of everyday life for children, adolescents, and adults. Recent theories have postulated a neuropsychological basis for social functioning with particularly strong links with the executive functioning (EF) system. The current study examined attention problems as a mediator between EF (e.g., working memory, planning, and response inhibition) and social functioning in a child and adolescent outpatient sample. Participants were 218 children ages 6-16 (M = 10.23; SD = 2.52; 68.8 % males) who were referred to an outpatient clinic for psychoeducational assessment. Bias corrected bootstrapping mediation analyses were used to examine the hypothesized models. The effects of working memory and planning (but not response inhibition) on social problems were mediated by attention problems in both teacher- and mother-reported models. These findings also held up in cross-source models (e.g., mother-reported attention problems as a mediator in a model predicting teacher reported social problems). These findings have implications for dimensional models of social functioning and conceptual models for specific clinical populations (e.g., attention-deficit/hyperactivity disorder). PMID- 27558394 TI - The Long-Term Effectiveness of the Family Check-up on Peer Preference: Parent Child Interaction and Child Effortful Control as Sequential Mediators. AB - We examined the longitudinal effects of the Family Check-Up (FCU) intervention beginning in toddlerhood on children's peer preference at school-age. Specifically, a sequential mediational model was proposed in which the FCU was hypothesized to promote peer preference (i.e., higher acceptance and lower rejection by peers) in middle childhood through its positive effects on parent child interaction and child effortful control in early childhood. Participants were 731 low-income families (49 % female). Qualities of parent-child interaction were observed during structured activities at 2 to 5 years, child effortful control was assessed using behavioral tasks at 5 years, and peer acceptance and rejection were rated by teachers at 7.5 to 10.5 years. Results indicated that the FCU indirectly predicted peer preference by sequentially improving parent-child interaction and child effortful control. The findings are discussed with respect to implications for understanding mechanisms by which early parenting-focused programs may enhance child functioning across time and context. PMID- 27558395 TI - Does degree of alteration in effort sense caused by eccentric exercise significantly affect initial exercise hyperpnea in humans? AB - Previous research has shown an exaggeration in exercise hyperpnea 2 days after eccentric exercise (ECC). Enhancement in central command has been suggested as one candidate to account for this effect given that ECC-induced neuromuscular dysfunction increases relative exercise intensity, thus resulting in reinforcement of effort sense. The purpose of this study was, therefore, to elucidate whether the degree of alteration in effort sense caused by ECC affects exercise hyperpnea. Ten subjects performed 20-s single-arm extension-flexion exercises with weight strapped to the wrist, and ventilatory response was measured before (Pre) and 2 days after ECC (D2). Relative exercise intensity at Pre was 5 % of maximal voluntary contraction (MVC) of Pre, whereas that at D2 was 9 % MVC of D2 because of decline in muscle strength. Ventilatory responses were significantly exaggerated at D2 with a significant increase in effort sense. Although effort sense was significantly reduced during exercise at D2 when wrist weight was subtracted to match relative exercise intensity at Pre (5 % MVC of D2), ventilatory responses were still significantly higher than those of Pre. After the disappearance of post-ECC muscle damage, subjects performed the same exercise with weight added (9 % MVC of Pre) so that effort was equalized to match that of D2; however, no significant increase in ventilatory response was detected. The fact that the extent of change in effort sense caused by ECC induced neuromuscular dysfunction did not affect ventilatory response at the onset of exercise after ECC may suggest that the exaggeration of ventilatory response after ECC is caused by mechanisms other than alteration of the central command. PMID- 27558396 TI - High trans but not saturated fat beverage causes an acute reduction in postprandial vascular endothelial function but not arterial stiffness in humans. AB - A diet high in trans-fatty acids (TFAs) is associated with a higher risk of cardiovascular disease (CVD) than a diet high in saturated fatty acids (SFAs), but the mechanisms remain unclear. We hypothesized that a beverage high in TFAs would cause a larger reduction in postprandial endothelial function and an increase in arterial stiffness, in part from greater reductions in insulin sensitivity, compared with a beverage high in SFAs. Eleven healthy adults (aged 47+/-5 years) ingested a warm test beverage (520 kcal, 56 g total fat, 5 g carbohydrate, 1 g protein) high in either TFAs or SFAs in a randomized cross-over study. Ingestion of the beverage high in TFAs (p<0.01) but not high in SFAs (p=0.49) decreased endothelial function (brachial artery flow-mediated dilation, mmDelta) at 3-4 hours (p<0.01 for time; p=0.034 for interaction), but did not alter aortic stiffness or carotid beta-stiffness. The homeostasis model of insulin resistance (interaction p=0.062) tended to decrease after SFAs but not TFAs. A beverage high in TFAs but not SFAs results in a postprandial reduction in endothelial function and a trend for decreased insulin sensitivity, potentially explaining the higher risk of CVD with a diet high in TFAs. PMID- 27558397 TI - Tuberculosis progression rates in U.S. Immigrants following screening with interferon-gamma release assays. AB - BACKGROUND: Interferon-gamma release assays may be used as an alternative to the tuberculin skin test for detection of M. tuberculosis infection. However, the risk of active tuberculosis disease following screening using interferon-gamma release assays in immigrants is not well defined. To address these uncertainties, we determined the incidence rates of active tuberculosis disease in a cohort of high-risk immigrants with Class B TB screened with interferon-gamma release assays (IGRAs) upon arrival in the United States. METHODS: Using a retrospective cohort design, we enrolled recent U.S. immigrants with Class B TB who were screened with an IGRA (QuantiFERON (r) Gold or Gold In-Tube Assay) at the San Francisco Department of Public Health Tuberculosis Control Clinic from January 2005 through December 2010. We reviewed records from the Tuberculosis Control Patient Management Database and from the California Department of Public Health Tuberculosis Case Registry to determine incident cases of active tuberculosis disease through February 2015. RESULTS: Of 1233 eligible immigrants with IGRA screening at baseline, 81 (6.6 %) were diagnosed with active tuberculosis disease as a result of their initial evaluation. Of the remaining 1152 participants without active tuberculosis disease at baseline, 513 tested IGRA-positive and 639 tested IGRA-negative. Seven participants developed incident active tuberculosis disease over 7730 person-years of follow-up, for an incidence rate of 91 per 100,000 person-years (95 % CI 43-190). Five IGRA-positive and two IGRA-negative participants developed active tuberculosis disease (incidence rates 139 per 100,000 person-years (95 % CI 58-335) and 48 per 100,000 person-years (95 % CI 12 193), respectively) for an unadjusted incidence rate ratio of 2.9 (95 % CI 0.5 30, p = 0.21). IGRA test results had a negative predictive value of 99.7 % but a positive predictive value of only 0.97 %. CONCLUSIONS: Among high-risk immigrants without active tuberculosis disease at the time of entry into the United States, risk of progression to active tuberculosis disease was higher in IGRA-positive participants compared with IGRA-negative participants. However, these findings did not reach statistical significance, and a positive IGRA at enrollment had a poor predictive value for progressing to active tuberculosis disease. Additional research is needed to identify biomarkers and develop clinical algorithms that can better predict progression to active tuberculosis disease among U.S. immigrants. PMID- 27558398 TI - Can baseline serum microRNAs predict response to TNF-alpha inhibitors in rheumatoid arthritis? AB - BACKGROUND: In rheumatoid arthritis, prediction of response to TNF-alpha inhibitor (TNFi) treatment would be of clinical value. This study aims to discover miRNAs that predict response and aims to replicate results of two previous studies addressing this topic. METHODS: From the observational BiOCURA cohort, 40 adalimumab- (ADA) and 40 etanercept- (ETN) treated patients were selected to enter the discovery cohort and baseline serum profiling on 758 miRNAs was performed. The added value of univariately selected miRNAs (p < 0.05) over clinical parameters in prediction of response was determined by means of the area under the receiver operating characteristic curve (AUC-ROC). Validation was performed by TaqMan single qPCR assays in 40 new patients. RESULTS: Expression of miR-99a and miR-143 predicted response to ADA, and miR-23a and miR-197 predicted response to ETN. The addition of miRNAs increased the AUC-ROC of a model containing only clinical parameters for ADA (0.75 to 0.97) and ETN (0.68 to 0.78). In validation, none of the selected miRNAs significantly predicted response. miR-23a was the only overlapping miRNA compared to the two previous studies, however inversely related with response in one of these studies. The reasons for the inability to replicate previously proposed miRNAs predicting response to TNFi and replicate those from the discovery cohort were investigated and discussed. CONCLUSIONS: To date, no miRNA consistently predicting response to TNFi therapy in RA has been identified. Future studies on this topic should meet a minimum of standards in design that are addressed in this study, in order to increase the reproducibility. PMID- 27558399 TI - Recent evolution of the salivary mucin MUC7. AB - Genomic structural variants constitute the majority of variable base pairs in primate genomes and affect gene function in multiple ways. While whole gene duplications and deletions are relatively well-studied, the biology of subexonic (i.e., within coding exon sequences), copy number variation remains elusive. The salivary MUC7 gene provides an opportunity for studying such variation, as it harbors copy number variable subexonic repeat sequences that encode for densely O glycosylated domains (PTS-repeats) with microbe-binding properties. To understand the evolution of this gene, we analyzed mammalian and primate genomes within a comparative framework. Our analyses revealed that (i) MUC7 has emerged in the placental mammal ancestor and rapidly gained multiple sites for O-glycosylation; (ii) MUC7 has retained its extracellular activity in saliva in placental mammals; (iii) the anti-fungal domain of the protein was remodified under positive selection in the primate lineage; and (iv) MUC7 PTS-repeats have evolved recurrently and under adaptive constraints. Our results establish MUC7 as a major player in salivary adaptation, likely as a response to diverse pathogenic exposure in primates. On a broader scale, our study highlights variable subexonic repeats as a primary source for modular evolutionary innovation that lead to rapid functional adaptation. PMID- 27558400 TI - Uncovering students' misconceptions by assessment of their written questions. AB - BACKGROUND: Misconceptions are ideas that are inconsistent with current scientific views. They are difficult to detect and refractory to change. Misconceptions can negatively influence how new concepts in science are learned, but are rarely measured in biomedical courses. Early identification of misconceptions is of critical relevance for effective teaching, but presents a difficult task for teachers as they tend to either over- or underestimate students' prior knowledge. A systematic appreciation of the existing misconceptions is desirable. This explorative study was performed to determine whether written questions generated by students can be used to uncover their misconceptions. METHODS: During a small-group work (SGW) session on Tumour Pathology in a (bio)medical bachelor course on General Pathology, students were asked to write down a question about the topic. This concerned a deepening question on disease mechanisms and not mere factual knowledge. Three independent expert pathologists determined whether the content of the questions was compatible with a misconception. Consensus was reached in all cases. Study outcomes were to determine whether misconceptions can be identified in students' written questions, and if so, to measure the frequency of misconceptions that can be encountered, and finally, to determine if the presence of such misconceptions is negatively associated with the students' course formal examination score. A subgroup analysis was performed according to gender and discipline. RESULTS: A total of 242 students participated in the SGW sessions, of whom 221 (91 %) formulated a question. Thirty-six questions did not meet the inclusion criteria. Of the 185 questions rated, 11 % (n = 20) was compatible with a misconception. Misconceptions were only found in medical students' questions, not in biomedical science students' questions. Formal examination score on Tumour Pathology was 5.0 (SD 2.0) in the group with misconceptions and 6.7 (SD 2.4) in the group without misconceptions (p = 0.003). CONCLUSIONS: This study demonstrates that misconceptions can be uncovered in students' written questions. The occurrence of these misconceptions was negatively associated with the formal examination score. Identification of misconceptions creates an opportunity to repair them during the remaining course sessions, in advance of the formal examination. PMID- 27558402 TI - Long-term Care Trajectories in Canadian Context: Patterns and Predictors of Publicly Funded Care. AB - Objectives: Drawing on a structural life course perspective (LCP), we examined the most common trajectories experienced by older long-term care (LTC; home and community-based care, assisted living, and nursing home care) recipients. The overall sequencing of care transitions was considered along with the role of social structural location, social and economic resources, and health factors in influencing them. Method: Latent class and latent transition analyses were conducted using administrative data obtained over a 4-year period for clients aged 65 and older (n = 2,951) admitted into publicly funded LTC in 1 Canadian health region. Results: Four main LTC trajectories were identified within which a wider range of more specific or secondary subtrajectories were embedded. These were shaped by social structural factors (age, gender, rural-urban residence), social and economic resources (marital status, income, payment for services), and health factors (chronic conditions, functional and cognitive impairment and decline, problematic behaviors). Discussion: Our findings support the utility of a structural LCP for understanding LTC trajectories in later life. In doing so, they also reveal avenues for enhancing equitable access to care and the need for options that would increase continuity and minimize unnecessary, untimely, or undesirable transitions. PMID- 27558403 TI - Has the Digital Health Divide Widened? Trends of Health-Related Internet Use Among Older Adults From 2003 to 2011. AB - Objectives: To examine the trend of health-related Internet use (HRIU) among older adults. Methods: We analyzed data from the 2003, 2005, and 2011-2012 iterations of the National Cancer Institute (NCI)-sponsored Health Information National Trends Survey (HINTS). HRIU was measured by 4 online behaviors: seeking health information, buying medicine, connecting with people with similar health problems, and communicating with doctors. Results: Internet use and HRIU among older adults increased substantially from 2003 to 2011 with more significant increases in seeking health information and communicating with doctors online. Overall, the digital health divide between different demographic groups has narrowed, especially in terms of gender, racial/ethnic group, rural/urban residence, and various health statuses; however, age, education, and household income remain persistent predictors of the digital divide. Those in the oldest group (75 or older), those with less than a high school education, and those with very low income (<$25,000/year) continuously lagged behind their counterparts in all aspects of HRIU. Conclusions: Despite an overall increase in HRIU and a narrowed digital divide, significant variations in HRIU in different demographic groups persisted; therefore, we call for more senior-friendly online resources and culturally appropriate interventions to bridge the digital health divide for vulnerable older adults. PMID- 27558407 TI - Clinical Connections. PMID- 27558405 TI - Financial Disclosure Information on One Author in the Article by Cartin-Ceba et al (Arthritis Rheumatol, June 2016). PMID- 27558404 TI - Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society. AB - Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care. PMID- 27558401 TI - Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint? AB - Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis. The interrelated multiple hypotheses that are presented for the first time in this article are extension of author's earlier series of 'accidental' discoveries on the role of inflammation in developmental stages of immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of data on chronic diseases suggest that nearly all age-associated illnesses, generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g., hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g., accelerated neurodegenerative and autoimmune diseases or site-specific cancers and metastasis) are variations of hypersensitivity responses of tissues that are manifested as different diseases in immune-responsive or immune-privileged tissues. Continuous release/presence of low level histamine (subclinical) in circulation could contribute to sustained oxidative stress and induction of 'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms of cumulative delayed hypersensitivity responses that would induce immunological chaos in favor of tissue growth in target tissues. Shared or special features of growth from fetus development into adulthood and aging processes and carcinogenesis are briefly compared with regard to energy requirements of highly complex function of Yin and Yang. Features of Yang (growth-promoting) arm of acute inflammation during fetus and cancer growth will be compared for consuming low energy from glycolysis (Warburg effect). Growth of fetus and cancer cells under hypoxic conditions and impaired mitochondrial energy requirements of tissues including metabolism of essential branched amino acids (e.g., val, leu, isoleu) will be compared for proposing a working model for future systematic research on cancer biology, prevention and therapy. Presentation of a working model provides insightful clues into bioenergetics that are required for fetus growth (absence of external threat and lack of high energy-demands of Yin events and parasite-like survival in host), normal growth in adulthood (balance in Yin and Yang processes) or disease processes and carcinogenesis (loss of balance in Yin-Yang). Future studies require focusing on dynamics and promotion of natural/inherent balance between Yin (tumoricidal) and Yang (tumorigenic) of effective immunity that develop after birth. Lawless growth of cancerous cells and loss of cell contact inhibition could partially be due to impaired mitochondria (mitophagy) that influence metabolism of branched chain amino acids for biosynthesis of structural proteins. The author invites interested scientists with diverse expertise to provide comments, confirm, dispute and question and/or expand and collaborate on many components of the proposed working model with the goal to better understand cancer biology for future designs of cost-effective research and clinical trials and prevention of cancer. Initial events during oxidative stress-induced damages to DNA/RNA repair mechanisms and inappropriate expression of inflammatory mediators are potentially correctable, preventable or druggable, if future studies were to focus on systematic understanding of early altered immune response dynamics toward multistep chronic diseases and carcinogenesis. PMID- 27558408 TI - Properties of Boolean dynamics by node classification using feedback loops in a network. AB - BACKGROUND: Biological networks keep their functions robust against perturbations. Many previous studies through simulations or experiments have shown that feedback loop (FBL) structures play an important role in controlling the network robustness without fully explaining how they do it. Hence, there is a pressing need to more rigorously analyze the influence of FBL structures on network robustness. RESULTS: In this paper, I propose a novel node classification notion based on the FBL structures involved. More specifically, I classify a node as a no-FBL-in-upstream (NFU) or no-FBL-in-downstream (NFD) node if no feedback loop is involved with any upstream or downstream path of the node, respectively. Based on those definitions, I first prove that every NFU node is eventually frozen in Boolean dynamics. Thus, NFU nodes converge to a fixed value determined by the upstream source nodes. Second, I prove that a network is robust against an arbitrary state perturbation subject to a non-source NFD node. This implies that a network state eventually sustains the attractor despite a perturbation subject to a non-source NFD node. Inspired by this result, I further propose a perturbation-sustainable probability that indicates how likely a perturbation effect is to be sustained through propagations. I show that genes with a high perturbation-sustainable probability are likely to be essential, disease, and drug-target genes in large human signaling networks. CONCLUSION: Taken together, these results will promote understanding of the effects of FBL on network robustness in a more rigorous manner. PMID- 27558410 TI - T Cell responses: Defective mitochondria disrupt CD8(+) T cells. PMID- 27558409 TI - Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans. AB - Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans. PMID- 27558411 TI - Asthma and allergy: Old McDonald had a farm (but no asthma)! PMID- 27558412 TI - Central sensitization as a determinant of patients' benefit from total hip and knee replacement. AB - BACKGROUND: Discrepancies exist between osteoarthritic joint changes and pain severity before and after total hip (THR) and knee (TKR) replacement. This study investigated whether the interaction between pre-operative widespread hyperalgesia and severity of radiographic osteoarthritis (OA) was associated with pain severity before and after joint replacement. METHODS: Data were analysed from 232 patients receiving THR and 241 receiving TKR. Pain was assessed pre operatively and at 12 months post-operatively using the WOMAC Pain Scale. Widespread hyperalgesia was assessed through forearm pressure pain thresholds (PPTs). Radiographic OA was evaluated using the Kellgren and Lawrence scheme. Statistical analysis was conducted using multilevel models, and adjusted for confounding variables. RESULTS: Pre-operative: In knee patients, there was weak evidence that the effect of PPTs on pain severity was greater in patients with more severe OA (Grade 3 OA: beta = 0.96 vs. Grade 4: beta = 4.03), indicating that in these patients higher PPTs (less widespread hyperalgesia) was associated with less severe pain. In hip patients, the effect of PPTs on pain did not differ with radiographic OA (Grade 3 OA: beta = 3.95 vs. Grade 4: beta = 3.67). Post operative: There was weak evidence that knee patients with less severe OA who had greater widespread hyperalgesia benefitted less from surgery (Grade 3 OA: beta = 2.28; 95% CI -1.69 to 6.25). Conversely, there was weak evidence that hip patients with more severe OA who had greater widespread hyperalgesia benefitted more from surgery (Grade 4 OA: beta = -2.92; 95% CI -6.58 to 0.74). CONCLUSIONS: Widespread sensitization may be a determinant of how much patients benefit from joint replacement, but the effect varies by joint and severity of structural joint changes. SIGNIFICANCE: Pre-operative widespread hyperalgesia and radiographic osteoarthritis (OA) severity may influence how much patients benefit from joint replacement. Patients undergoing knee replacement with less severe OA and greater widespread hyperalgesia benefitted less from surgery than patients with less hyperalgesia. Patients undergoing hip replacement with more severe OA and greater widespread hyperalgesia benefitted more than patients with less hyperalgesia. PMID- 27558413 TI - pH-Responsive Core-Shell Structured Nanoparticles for Triple-Stage Targeted Delivery of Doxorubicin to Tumors. AB - The application of cytotoxic chemotherapeutics in cancer therapy has been largely restricted by their lack of selectivity. Despite the existence of numerous targeted delivery systems, it is practically challenging to develop one single system to simultaneously cover tumor-targeted delivery of chemotherapeutics at the tissue, cellular, and subcellular levels. To solve this problem, pH responsive core-shell structured nanoparticles (CSNPs) were self-assembled in this study to provide triple-stage targeted delivery of doxorubicin (DOX) from the injection site to the nuclei of cancer cells. Amino-functionalized mesoporous silica nanoparticles (MSN) were doubly modified with TAT peptide and acid cleavable polyethylene glycol (PEG) as the DOX-loaded cationic core. The anionic shell was constituted by galactose-modified poly(allylamine hydrochloride) citraconic anhydride, a hepato-carcinoma-targeting polymer with charge-reversible property. In vitro results showed that PEG effectively reduced protein adsorption and phagocytic capture of CSNPs in the circulating blood (pH 7.4), thus facilitating passive accumulation in tumors (tissue level). Following PEG detachment via acidic hydrolysis in tumor microenvironment (pH 6.5), the exposed galactose ligands endowed CSNPs with active internalization into hepato-carcinoma cells (cellular level). Afterward, the acidity in endosomes and lysosomes (pH 5.0) triggered the conversion of anionic shell into positive charges, leading to core-shell disassembly and subsequent TAT-mediated delivery of DOX to the nuclei (subcellular level). Importantly, the efficiencies of each targeting moiety were nicely preserved when combining together in CSNPs. As a result, improved tumorous distribution and potent therapeutic efficacy of CSNPs were noted in tumor-bearing mice at a relatively low dose. CSNPs therefore provide an efficient and nontoxic platform for the targeted delivery of antitumor drugs. PMID- 27558415 TI - Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes. AB - : Mouse hepatitis virus strain A59 infection of mice is a useful tool for studying virus-host interaction during hepatitis development. The NS2H126R mutant is attenuated in liver replication due to loss of phosphodiesterase activity, which the wild-type (WT) virus uses to block the 2',5'-oligoadenylate synthetase (OAS)-RNase L (RNase L) antiviral pathway. The activation of RNase L by NS2H126R is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We tested the hypothesis that the resident liver macrophages, Kupffer cells (KC), represent the cell type most likely to restrict NS2H126R and prevent hepatitis. As found previously, A59 and NS2H126R replicate similarly in hepatocytes and neither activates RNase L, as assessed by an rRNA degradation assay. In contrast, in KC, A59 exhibited a 100-fold-higher titer than NS2H126R and NS2H126R induced rRNA degradation. Interestingly, in liver sinusoidal endothelial cells (LSEC), the cells that form a barrier between blood and liver parenchymal cells, NS2H126R activates RNase L, which limits viral replication. Similar growth kinetics were observed for the two viruses in KC and LSEC from RNase L-/- mice, demonstrating that both use RNase L to limit NS2H126R replication. Depletion of KC by gadolinium(III) chloride or of LSEC by cyclophosphamide partially restores liver replication of NS2H126R, leading to hepatitis. Thus, during mouse hepatitis virus (MHV) infection, hepatitis, which damages the parenchyma, is prevented by RNase L activity in both KC and LSEC but not in hepatocytes. This may be explained by the undetectable levels of RNase L as well as by the OASs expressed in hepatocytes. IMPORTANCE: Mouse hepatitis virus infection of mice provides a useful tool for studying virus-host interactions during hepatitis development. The NS2H126R mutant is attenuated in liver replication due to loss of phosphodiesterase activity, by which the wild type virus blocks the potent OAS-RNase L antiviral pathway. RNase L activation by NS2H126R is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We showed that the hepatocytes that comprise the liver parenchyma do not activate RNase L when infected with NS2H126R or restrict replication. However, both Kupffer cells (KC) (i.e., the liver-resident macrophages) and the liver sinusoidal endothelial cells (LSEC) which line the sinusoids activate RNase L in response to NS2H126R These data suggest that KC and LSEC prevent viral spread into the parenchyma, preventing hepatitis. Furthermore, hepatocytes express undetectable levels of OASs and RNase L, which likely explains the lack of RNase L activation during NS2H126R infection. PMID- 27558414 TI - Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax. AB - : To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XL abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. IMPORTANCE: EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. This study provides evidence that EV71 induces cell apoptosis by modulating Bax activation and reveals important clues regarding the mechanism of Cyt c release and mitochondrial permeabilization during EV71 infection. PMID- 27558416 TI - Cell Surface THY-1 Contributes to Human Cytomegalovirus Entry via a Macropinocytosis-Like Process. AB - : Previously we showed that THY-1 has a critical role in the initial stage of infection of certain cell types with human cytomegalovirus (HCMV) and that THY-1 is important for HCMV-mediated activation of phosphatidylinositol 3-kinase (PI3K)/Akt during virus entry. THY-1 is known to interact with integrins and is a major cargo protein of clathrin-independent endocytic vesicles. Since macropinocytosis involves integrin signaling, is PI3K/Akt dependent, and is a clathrin-independent endocytic process, we determined whether THY-1 has a role in HCMV entry by macropinocytosis. Using electron microscopy in two cell lines that support HCMV infection in a THY-1-dependent manner, we found that HCMV enters these cells by a macropinocytosis-like process. THY-1 associated with HCMV virions on the cell surface and colocalized with virus inside macropinosomes. 5 (N-Ethyl-N-isopropyl)amiloride (EIPA) and soluble THY-1 blocked HCMV infection in the cell lines by >=80% and 60%, respectively. HCMV entry into the cells triggered increased influx of extracellular fluid, a marker of macropinocytosis, and this increased fluid uptake was inhibited by EIPA and by soluble THY-1. Blocking actin depolymerization, Na+/H+ exchange, PI3K, and Pak1 kinase, which are critical for macropinocytosis, impaired HCMV infection. Neither internalized HCMV virions nor THY-1 in virus-infected cells colocalized with transferrin as determined by confocal microscopy, indicating that clathrin-mediated endocytosis was not involved in THY-1-associated virus entry. These results suggest that HCMV has adapted to utilize THY-1, a cargo protein of clathrin-independent endocytotic vesicles, to facilitate efficient entry into certain cell types by a macropinocytosis-like process. IMPORTANCE: Human cytomegalovirus (HCMV) infects over half of the population and is the most common infectious cause of birth defects. The virus is the most important infection occurring in transplant recipients. The mechanism of how HCMV enters cells is controversial. In this study, we show that THY-1, a cell surface protein that is critical for the early stage of entry of HCMV into certain cell types, contributes to virus entry by macropinocytosis. Our findings suggest that HCMV has adapted to utilize THY-1 to facilitate entry of HCMV into macropinosomes in certain cell types. Further knowledge about the mechanism of HCMV entry into cells may facilitate the development of novel inhibitors of virus infection. PMID- 27558417 TI - LFA-1 Engagement Triggers T Cell Polarization at the HIV-1 Virological Synapse. AB - : HIV-1 efficiently disseminates by cell-cell spread at intercellular contacts called virological synapses (VS), where the virus preferentially assembles and buds. Cell-cell contact triggers active polarization of organelles and viral proteins within infected cells to the contact site to support efficient VS formation and HIV-1 spread; critically, however, which cell surface protein triggers contact-induced polarization at the VS remains unclear. Additionally, the mechanism by which the HIV-1 envelope glycoprotein (Env) is recruited to the VS remains ill defined. Here, we use a reductionist bead-coupled antibody assay as a model of the VS and show that cross-linking the integrin LFA-1 alone is sufficient to induce active T cell polarization and recruitment of the microtubule organizing center (MTOC) in HIV-1-infected cells. Mutant cell lines coupled with inhibitors demonstrated that LFA-1-induced polarization was dependent on the T cell kinase ZAP70. Notably, immunofluorescent staining of viral proteins revealed an accumulation of surface Env at sites of LFA-1 engagement, with intracellular Env localized to a Golgi compartment proximal to the polarized MTOC. Furthermore, blocking LFA-1-induced MTOC polarization through ZAP70 inhibition prevented intracellular Env polarization. Taken together, these data reveal that LFA-1 is a key determinant in inducing dynamic T cell remodeling to the VS and suggest a model in which LFA-1 engagement triggers active polarization of the MTOC and the associated Env-containing secretory apparatus to sites of cell-cell contact to support polarized viral assembly and egress for efficient cell-cell spread. IMPORTANCE: HIV-1 causes AIDS by spreading within immune cells and depletion of CD4 T lymphocytes. Rapid spread between these cells occurs by highly efficient cell-cell transmission that takes place at virological synapses (VS). VS are characterized by striking T cell remodeling that is spatially associated with polarized virus assembly and budding at sites of cell contact. Here, we show that the integrin LFA-1 triggers organelle polarization and viral protein recruitment, facilitating formation of the VS, and that this requires the T cell kinase ZAP70. Taken together, these data suggest a mechanism by which HIV-1-infected T cells sense and respond to cell contact to polarize viral egress and promote cell-cell spread. Understanding how cell-cell spread is regulated may help reveal therapeutic targets to specifically block this mode of HIV-1 dissemination. PMID- 27558418 TI - Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism. AB - : Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2. Fluorescence in situ hybridization of AAV transgenes was used to identify differences in retinal trafficking and revealed that HS binding was responsible for AAV2 accumulation at the ILM. This mechanism was tested on human ex vivo retinas and showed similar accumulation with HS-binding AAV2 capsid only. To evaluate if HS binding could be applied to other AAV serotypes to enhance their transduction, AAV1 and AAV8 were modified to bind HS with a single-amino-acid mutation and tested in mice. Both HS-binding mutants of AAV1 and AAV8 had higher intravitreal transduction than their non-HS-binding parent capsid due to increased retinal accumulation. To understand the influence that HS binding has on tropism, chimeric AAV2 capsids with dual-glycan usage were tested intravitreally in mice. Compared to HS binding alone, these chimeric capsids displayed enhanced transduction that was correlated with a change in tropism. Taken together, these data indicate that HS binding serves to sequester AAV capsids from the vitreous to the ILM but does not influence retinal tropism. The enhanced retinal transduction of HS-binding capsids provides a rational design strategy for engineering capsids for intravitreal delivery. IMPORTANCE: Adeno associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy is met by intravitreal delivery, but delivery of AAV by this route results in poor transduction outcomes. The inner limiting membrane (ILM) creates a barrier separating the vitreous and the retina. Binding of AAV to heparan sulfate proteoglycan (HSPG) at the ILM may allow the virus to traverse this barrier for better retinal transduction. We show that HSPG binding is correlated with greater accumulation and penetration of AAV in the retina. We demonstrated that this accumulation is conserved across mouse and human retinas and that the addition of HSPG binding to other AAV capsids can increase the number of vectors accumulating at the ILM without dictating tropism. PMID- 27558419 TI - Monocytes but Not Lymphocytes Carrying HIV-1 on Their Surface Transmit Infection to Human Tissue Ex Vivo. AB - : Unprotected sexual intercourse with HIV-infected men is the major cause of new infections. HIV virions are released into semen by various cells of the male genital tract, as well as by infected monocytes and lymphocytes present in semen. Some of these virions may attach to the surfaces of cells, infected or uninfected. We investigated whether cells carrying attached HIV on their surfaces can transmit infection. We addressed this question in a model system of human tissue exposed ex vivo to monocytes and lymphocytes carrying HIV on their surfaces. We gamma irradiated the cells to prevent their productive infection. In spite of comparable amounts of HIV attached to monocytes and lymphocytes, only monocytes were capable of transmitting infection and triggering productive infection in tissue. This HIV-1 transmission was mediated by cell-cell contacts. Our experiments suggest that in vivo, HIV attached to infected or uninfected monocytes, which far outnumber lymphocytes in HIV-infected semen, may contribute to sexual transmission of HIV from men to their partners. IMPORTANCE: The vast majority of new HIV infections occur through sexual transmission, in which HIV is transferred from the semen of an infected male to an uninfected partner. In semen, HIV-1 particles may exist as free-floating virions; inside infected cells; or attached to the surfaces of cells, whether they are infected or not. Here, we investigated whether HIV attached to the surfaces of monocytes or lymphocytes could transmit infection to human tissue. Incubation of human tissue with monocyte-attached HIV resulted in productive tissue infection. In contrast, there was no infection of tissues when they were incubated with lymphocyte-attached HIV 1. Our results highlight the important role that seminal monocytes may play in HIV transmission in vivo, especially since monocytes far outnumber lymphocytes in the semen of HIV-infected individuals. PMID- 27558420 TI - A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice. AB - : H9N2 avian influenza virus (AIV) has an extended host range, but the molecular basis underlying H9N2 AIV transmission to mammals remains unclear. We isolated more than 900 H9N2 AIVs in our 3-year surveillance in live bird markets in China from 2009 to 2012. Thirty-seven representative isolates were selected for further detailed characterization. These isolates were categorized into 8 genotypes (B64 to B71) and formed a distinct antigenic subgroup. Three isolates belonging to genotype B69, which is a predominant genotype circulating in China, replicated efficiently in mice, while the viruses tested in parallel in other genotypes replicated poorly, although they, like the three B69 isolates, have a leucine at position 226 in the hemagglutinin (HA) receptor binding site, which is critical for binding human type sialic acid receptors. Further molecular and single mutation analysis revealed that a valine (V) residue at position 190 in HA is responsible for efficient replication of these H9N2 viruses in mice. The 190V in HA does not affect virus receptor binding specificity but enhances binding affinity to human cells and lung tissues from mouse and humans. All these data indicate that the 190V in HA is one of the important determinants for H9N2 AIVs to cross the species barrier to infect mammals despite multiple genes conferring adaptation and replication of H9N2 viruses in mammals. Our findings provide novel insights on understanding host range expansion of H9N2 AIVs. IMPORTANCE: Influenza virus hemagglutinin (HA) is responsible for binding to host cell receptors and therefore influences the viral host range and pathogenicity in different species. We showed that the H9N2 avian influenza viruses harboring 190V in the HA exhibit enhanced virus replication in mice. Further studies demonstrate that 190V in the HA does not change virus receptor binding specificity but enhances virus binding affinity of the H9N2 virus to human cells and attachment to lung tissues from humans and mouse. Our findings suggest that more attention should be given to the H9N2 AIVs with HA-190V during surveillance due to their potential threat to mammals, including humans. PMID- 27558421 TI - HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. AB - : Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of >=90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1 neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals. IMPORTANCE: Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV 1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1 neutralizing IgA in the on-PrEP group than in the placebo group. PMID- 27558422 TI - CD95 Signaling Inhibits B Cell Receptor-Mediated Gammaherpesvirus Replication in Apoptosis-Resistant B Lymphoma Cells. AB - : While CD95 is an apoptosis-inducing receptor and has emerged as a potential anticancer therapy target, mounting evidence shows that CD95 is also emerging as a tumor promoter by activating nonapoptotic signaling pathways. Gammaherpesviral infection is closely associated with lymphoproliferative diseases, including B cell lymphomas. The nonapoptotic function of CD95 in gammaherpesvirus-associated lymphomas is largely unknown. Here, we show that stimulation of CD95 agonist antibody drives the majority of sensitive gammaherpesvirus-transformed B cells to undergo caspase-dependent apoptosis and promotes the survival and proliferation of a subpopulation of apoptosis-resistant B cells. Surprisingly, CD95-mediated nonapoptotic signaling induced beta interferon (IFN-beta) expression and correlatively inhibited B cell receptor (BCR)-mediated gammaherpesviral replication in the apoptosis-resistant lymphoma cells without influencing BCR signaling. Further analysis showed that IFN-beta alone or synergizing with CD95 blocked the activation of lytic switch proteins and the gene expression of gammaherpesviruses. Our findings indicate that, independent of its apoptotic activity, CD95 signaling activity plays an important role in blocking viral replication in apoptosis-resistant, gammaherpesvirus-associated B lymphoma cells, suggesting a novel mechanism that indicates how host CD95 prototype death receptor controls the life cycle of gammaherpesviruses independent of its apoptotic activity. IMPORTANCE: Gammaherpesviruses are closely associated with lymphoid malignancies and other cancers. Viral replication and persistence strategies leading to cancer involve the activation of antiapoptotic and proliferation programs, as well as evasion of the host immune response. Here, we provide evidence that the stimulation of CD95 agonist antibody, mimicking one of the major mechanisms of cytotoxic T cell killing, inhibits B cell receptor mediated gammaherpesviral replication in CD95 apoptosis-resistant lymphoma cells. CD95-induced type I interferon (IFN-beta) contributes to the inhibition of gammaherpesviral replication. This finding sheds new light on the CD95 nonapoptotic function and provides a novel mechanism for gammaherpesviruses that helps them to escape host immune surveillance. PMID- 27558423 TI - Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduces the Number of Transmitted/Founder Viruses Established in Rhesus Macaques. AB - : AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4+ T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus. IMPORTANCE: The establishment of AIDS virus infection in an individual is essentially a race between the spreading virus and host immune defenses. Cell-mediated immune responses induced by infection or vaccination are important contributors in limiting viral replication. However, in human immunodeficiency virus (HIV)/SIV infection, the virus usually wins the race, irreversibly crippling the immune system before an effective cellular immune response is developed and active. We found that providing an accelerated response by adoptively transferring large numbers of antiviral T cells shortly after a high-dose mucosal inoculation, while not preventing infection altogether, limited the number of individual viruses transmitted. Thus, the presence of strong, preexisting T-cell responses, including those induced by vaccines, might prevent infection in humans, where the virus exposure is considerably lower. PMID- 27558424 TI - Characterization of Clade 7.2 H5 Avian Influenza Viruses That Continue To Circulate in Chickens in China. AB - : The H5N1 avian influenza viruses emerged in Southeast Asia in the late 20th century and have evolved into multiple phylogenetic clades based on their hemagglutinin (HA)-encoding genes. The clade 7.2 viruses were first detected in chickens in northern China in 2006, and vaccines specifically targeted to the clade were developed and have been used in poultry in China since 2006. During routine surveillance and disease diagnosis, we isolated seven H5 viruses between 2011 and 2014 that bear the clade 7.2 HA genes. Here, we performed extensive studies to understand how the clade 7.2 H5 viruses have evolved in chickens in China. Full genome sequence analysis revealed that the seven viruses formed two subtypes (four H5N1 viruses and three H5N2 viruses) and four genotypes by deriving genes from other influenza viruses. All of the viruses had antigenically drifted from the clade 7.2 viruses that were isolated in 2006. Pathogenicity studies of four viruses, one from each genotype, revealed that all of the viruses are highly pathogenic in chickens, but none of them could replicate in ducks. The four viruses exclusively bound to avian-type receptors and replicated only in the turbinates and/or lungs of mice; none of them were lethal to mice at a dosage of 106 50% egg infective doses (EID50). Our study indicates that although the clade 7.2 viruses have not been eradicated from poultry through vaccination, they have not become more dangerous to other animals (e.g., ducks and mice) and humans. IMPORTANCE: Animal influenza viruses can acquire the ability to infect and kill humans. The H5N1 viruses have been a concern in recent decades because of their clear pandemic potential. We sorted H5N1 influenza viruses into different phylogenetic clades based on their HA genes. The clade 7.2 viruses were detected in chickens in several provinces of northern China in 2006. Vaccines for these viruses were subsequently developed and have been used ever since to control infection of poultry. Here, we analyzed the genetic and biologic properties of seven clade 7.2 viruses that were isolated from chickens between 2011 and 2014. We found that after nearly 9 years of circulation in chickens, the clade 7.2 viruses still exclusively bind to avian-type receptors and are of low pathogenicity to mice, suggesting that these H5 viruses pose a low risk to human public health. PMID- 27558425 TI - Protein Primary Structure of the Vaccinia Virion at Increased Resolution AB - : Here we examine the protein covalent structure of the vaccinia virus virion. Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. A total of 63 host proteins were also identified as candidates for packaging. Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. We provide evidence for the phosphoglycosylation of vaccinia virus proteins. IMPORTANCE: Poxviruses are among the most complex and irregular virions, about whose internal structure little is known. To better understand poxvirus virion structure, imaging should be supplemented with other tools. Here, we provide a deep study of the covalent structure of the vaccinia virus virion using the various tools of contemporary mass spectrometry. PMID- 27558426 TI - An Essential Role of INI1/hSNF5 Chromatin Remodeling Protein in HIV-1 Posttranscriptional Events and Gag/Gag-Pol Stability. AB - : INI1/hSNF5/SMARCB1/BAF47 is an HIV-specific integrase (IN)-binding protein that influences HIV-1 transcription and particle production. INI1 binds to SAP18 (Sin3a-associated protein, 18 kDa), and both INI1 and SAP18 are incorporated into HIV-1 virions. To determine the significance of INI1 and the INI1-SAP18 interaction during HIV-1 replication, we isolated a panel of SAP18-interaction defective (SID)-INI1 mutants using a yeast reverse two-hybrid screen. The SID INI1 mutants, which retained the ability to bind to IN, cMYC, and INI1 but were impaired for binding to SAP18, were tested for their effects on HIV-1 particle production. SID-INI1 dramatically reduced the intracellular Gag/Gag-Pol protein levels and, in addition, decreased viral particle production. The SID-INI1 mediated effects were less dramatic in trans complementation assays using IN deletion mutant viruses with Vpr-reverse transcriptase (RT)-IN. SID-INI1 did not inhibit long-terminal-repeat (LTR)-mediated transcription, but it marginally decreased the steady-state gag RNA levels, suggesting a posttranscriptional effect. Pulse-chase analysis indicated that in SID-INI1-expressing cells, the pr55Gag levels decreased rapidly. RNA interference analysis indicated that small hairpin RNA (shRNA)-mediated knockdown of INI1 reduced the intracellular Gag/Gag Pol levels and further inhibited HIV-1 particle production. These results suggest that SID-INI1 mutants inhibit multiple stages of posttranscriptional events of HIV-1 replication, including intracellular Gag/Gag-Pol RNA and protein levels, which in turn inhibits assembly and particle production. Interfering INI1 leads to a decrease in particle production and Gag/Gag-Pol protein levels. Understanding the role of INI1 and SAP18 in HIV-1 replication is likely to provide novel insight into the stability of Gag/Gag-Pol, which may lead to the development of novel therapeutic strategies to inhibit HIV-1 late events. IMPORTANCE: Significant gaps exist in our current understanding of the mechanisms and host factors that influence HIV-1 posttranscriptional events, including gag RNA levels, Gag/Gag-Pol protein levels, assembly, and particle production. Our previous studies suggested that the IN-binding host factor INI1 plays a role in HIV-1 assembly. An ectopically expressed minimal IN-binding domain of INI1, S6, potently and selectively inhibited HIV-1 Gag/Gag-Pol trafficking and particle production. However, whether or not endogenous INI1 and its interacting partners, such as SAP18, are required for late events was unknown. Here, we report that endogenous INI1 and its interaction with SAP18 are necessary to maintain intracellular levels of Gag/Gag-Pol and for particle production. Interfering INI1 or the INI1-SAP18 interaction leads to the impairment of these processes, suggesting a novel strategy for inhibiting posttranscriptional events of HIV-1 replication. PMID- 27558427 TI - Glycan Specificity of P[19] Rotavirus and Comparison with Those of Related P Genotypes. AB - : The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike the other P[II] RVs, which mainly infect humans, P[19] RVs commonly infect animals (pigs), making P[19] unique for the study of RV diversity and host ranges. Through in vitro binding assays and saturation transfer difference (STD) nuclear magnetic resonance (NMR), we found that P[19] could bind mucin cores 2, 4, and 6, as well as type 1 histo-blood group antigens (HBGAs). The common sequences of these glycans serve as minimal binding units, while additional residues, such as the A, B, H, and Lewis epitopes of the type 1 HBGAs, can further define the binding outcomes and therefore likely the host ranges for P[19] RVs. This complex binding property of P[19] is shared with the other three P[II] RVs (P[4], P[6], and P[8]) in that all of them recognized the type 1 HBGA precursor, although P[4] and P[8], but not P[6], also bind to mucin cores. Moreover, while essential for P[4] and P[8] binding, the addition of the Lewis epitope blocked P[6] and P[19] binding to type 1 HBGAs. Chemical-shift NMR of P[19] VP8* identified a ligand binding interface that has shifted away from the known RV P-genotype binding sites but is conserved among all P[II] RVs and two P[I] RVs (P[10] and P[12]), suggesting an evolutionary connection among these human and animal RVs. Taken together, these data are important for hypotheses on potential mechanisms for RV diversity, host ranges, and cross-species transmission. IMPORTANCE: In this study, we found that our P[19] strain and other P[II] RVs recognize mucin cores and the type 1 HBGA precursors as the minimal functional units and that additional saccharides adjacent to these units can alter binding outcomes and thereby possibly host ranges. These data may help to explain why some P[II] RVs, such as P[6] and P[19], commonly infect animals but rarely humans, while others, such as the P[4] and P[8] RVs, mainly infect humans and are predominant over other P genotypes. Elucidation of the molecular bases for strain-specific host ranges and cross-species transmission of these human and animal RVs is important to understand RV epidemiology and disease burden, which may impact development of control and prevention strategies against RV gastroenteritis. PMID- 27558428 TI - Reduction of Neuraminidase Activity Exacerbates Disease in 2009 Pandemic Influenza Virus-Infected Mice. AB - : During the first wave of the 2009 pandemic, caused by a H1N1 influenza virus (pH1N1) of swine origin, antivirals were the only form of therapeutic available to control the proliferation of disease until the conventional strain-matched vaccine was produced. Oseltamivir is an antiviral that inhibits the sialidase activity of the viral neuraminidase (NA) protein and was shown to be effective against pH1N1 viruses in ferrets. Furthermore, it was used in humans to treat infections during the pandemic and is still used for current infections without reported complication or exacerbation of illness. However, in an evaluation of the effectiveness of oseltamivir against pH1N1 infection, we unexpectedly observed an exacerbation of disease in virus-infected mice treated with oseltamivir, transforming an otherwise mild illness into one with high morbidity and mortality. In contrast, an identical treatment regime alleviated all signs of illness in mice infected with the pathogenic mouse-adapted virus A/WSN/33 (H1N1). The worsened clinical outcome with pH1N1 viruses occurred over a range of oseltamivir doses and treatment schedules and was directly linked to a reduction in NA enzymatic activity. Our results suggest that the suppression of NA activity with antivirals may exacerbate disease in a host-dependent manner by increasing replicative fitness in viruses that are not optimally adapted for replication in that host. IMPORTANCE: Here, we report that treatment of pH1N1-infected mice with oseltamivir enhanced disease progression, transforming a mild illness into a lethal infection. This raises a potential pitfall of using the mouse model for evaluation of the therapeutic efficacy of neuraminidase inhibitors. We show that antiviral efficacy determined in a single animal species may not represent treatment in humans and that caution should be used when interpreting the outcome. Furthermore, increased virulence due to oseltamivir treatment was the effect of a shift in the hemagglutinin (HA) and neuraminidase (NA) activity balance. This is the first study that has demonstrated that altering the HA/NA activity balance by reduction in NA activity can result in an increase in virulence in any animal model from nonpathogenic to lethal and the first to demonstrate a situation in which treatment with a NA activity inhibitor has an effect opposite to the intended therapeutic effect of ameliorating the infection. PMID- 27558429 TI - Pathogenicity and Transmission of H5 and H7 Highly Pathogenic Avian Influenza Viruses in Mallards. AB - : Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses. IMPORTANCE: The spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the Gs/GD lineage by migratory waterfowl is a serious concern for animal and public health. H5 and H7 HPAI viruses are considered to be adapted to gallinaceous species (chickens, turkeys, quail, etc.) and less likely to infect and transmit in wild ducks. In order to understand why this is different with certain Gs/GD lineage H5 HPAI viruses, we compared the pathogenicity and transmission of several H5 and H7 HPAI viruses from previous poultry outbreaks to Gs/GD lineage H5 viruses, including H5N1 (clade 2.2), H5N8 and H5N2 (clade 2.3.4.4) viruses, in mallards as a representative wild duck species. Surprisingly, most HPAI viruses examined in this study replicated well and transmitted among mallards; however, the three Gs/GD lineage H5 HPAI viruses replicated to higher titers, which could explain the transmission of these viruses in susceptible wild duck populations. PMID- 27558432 TI - First Description of Shigella sonnei Harboring blaCTX-M-55 Outside Asia. AB - Shigella sonnei harboring blaCTX-M-55 was isolated outside of Asia for the first time. The blaCTX-M-55 gene was found to be downstream of ISEcp-1 and located in a ~130 kb conjugative plasmid belonging to the I1 incompatibility group. The strain was recovered from a 7-year-old Ecuadorian girl with watery diarrhea who had not travelled abroad. Recent local data describe the emergence of blaCTX-M-55 and other variants typically found in Asia in the Andean Region, suggesting that increased travel of humans and trade relationships with Asian countries are influencing the current Ecuadorian bacterial resistance situation. PMID- 27558430 TI - Affinity Purification of the Hepatitis C Virus Replicase Identifies Valosin Containing Protein, a Member of the ATPases Associated with Diverse Cellular Activities Family, as an Active Virus Replication Modulator. AB - : Like almost all of the positive-strand RNA viruses, hepatitis C virus (HCV) induces host intracellular membrane modification to form the membrane-bound viral replication complex (RC), within which viral replicases amplify the viral RNA genome. Despite accumulated information about how HCV co-opts host factors for viral replication, our knowledge of the molecular mechanisms by which viral proteins hijack host factors for replicase assembly has only begun to emerge. Purification of the viral replicase and identification of the replicase associated host factors to dissect their roles in RC biogenesis will shed light on the molecular mechanisms of RC assembly. To purify the viral replicase in the context of genuine viral replication, we developed an HCV subgenomic replicon system in which two different affinity tags were simultaneously inserted in frame into HCV NS5A and NS5B. After solubilizing the replicon cells, we purified the viral replicase by two-step affinity purification and identified the associated host factors by mass spectrometry. We identified valosin-containing protein (VCP), a member of the ATPases associated with diverse cellular activities (AAA+ATPase) family, as an active viral replication modulator whose ATPase activity is required for viral replication. A transient replication assay indicated that VCP is involved mainly in viral genome amplification. VCP associated with viral replicase and colocalized with a viral RC marker. Further, in an HCV replicase formation surrogate system, abolishing VCP function resulted in aberrant distribution of HCV NS5A. We propose that HCV may co-opt a host AAA+ATPase for its replicase assembly. IMPORTANCE: Almost all of the positive strand RNA viruses share a replication strategy in which viral proteins modify host membranes to form the membrane-associated viral replicase. Viruses hijack host factors to facilitate this energy-unfavorable process. Understanding of this fundamental process is hampered by the challenges of purifying the replicase because of the technical difficulties involved. In this study, we developed an HCV subgenomic replicon system in which two different affinity tags were simultaneously inserted in frame into two replicase components. Using this dual affinity-tagged replicon system, we purified the viral replicase and identified valosin-containing protein (VCP) AAA+ATPase as a pivotal viral replicase associated host factor that is required for viral genome replication. Abolishing VCP function resulted in aberrant viral protein distribution. We propose that HCV hijacks a host AAA+ATPase for its replicase assembly. Understanding the molecular mechanism of VCP regulates viral replicase assembly may lead to novel antiviral strategies targeting the most conserved viral replication step. PMID- 27558431 TI - Exploitation of Interleukin-10 (IL-10) Signaling Pathways: Alternate Roles of Viral and Cellular IL-10 in Rhesus Cytomegalovirus Infection. AB - : There is accumulating evidence that the viral interleukin-10 (vIL-10) ortholog of both human and rhesus cytomegalovirus (HCMV and RhCMV, respectively) suppresses the functionality of cell types that are critical to contain virus dissemination and help shape long-term immunity during the earliest virus-host interactions. In particular, exposure of macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic cells, and plasmacytoid dendritic cells to vIL-10 suppresses multiple effector functions including, notably, those that link innate and adaptive immune responses. Further, vaccination of RhCMV uninfected rhesus macaques with nonfunctional forms of RhCMV vIL-10 greatly restricted parameters of RhCMV infection following RhCMV challenge of the vaccinees. Vaccinees exhibited significantly reduced shedding of RhCMV in saliva and urine following RhCMV challenge compared to shedding in unvaccinated controls. Based on the evidence that vIL-10 is critical during acute infection, the role of vIL-10 during persistent infection was analyzed in rhesus macaques infected long term with RhCMV to determine whether postinfection vaccination against vIL-10 could change the virus-host balance. RhCMV-seropositive macaques, which shed RhCMV in saliva, were vaccinated with nonfunctional RhCMV vIL-10, and shedding levels of RhCMV in saliva were evaluated. Following robust increases in vIL-10-binding and vIL-10-neutralizing antibodies, shedding levels of RhCMV modestly declined, consistent with the interpretation that vIL-10 may play a functional role during persistent infection. However, a more significant association was observed between the levels of cellular IL-10 secreted in peripheral blood mononuclear cells exposed to RhCMV antigens and shedding of RhCMV in saliva. This result implies that RhCMV persistence is associated with the induction of cellular IL-10 receptor-mediated signaling pathways. IMPORTANCE: Human health is adversely impacted by viruses that establish lifelong infections that are often accompanied with increased morbidity and mortality (e.g., infections with HIV, hepatitis C virus, or human cytomegalovirus). A longstanding but unfulfilled goal has been to develop postinfection vaccine strategies that could "reboot" the immune system of an infected individual in ways that would enable the infected host to develop immune responses that clear reservoirs of persistent virus infection, effectively curing the host of infection. This concept was evaluated in rhesus macaques infected long term with rhesus cytomegalovirus by repeatedly immunizing infected animals with nonfunctional versions of the rhesus cytomegalovirus-encoded viral interleukin-10 immune modulating protein. Following vaccine-mediated boosting of antibody titers to viral interleukin-10, there was modest evidence for increased immunological control of the virus following vaccination. More significantly, data were also obtained that indicated that rhesus cytomegalovirus is able to persist due to upregulation of the cellular interleukin-10 signaling pathway. PMID- 27558433 TI - Fructus Amomi Cardamomi Extract Inhibit Coxsackievirus-B3 Induced Myocarditis in Murine Myocarditis Model. AB - Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations (100-10 ug/ml). CVB3 capsid protein VP1 expression (76%) and viral protease 2A induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract (100 ug/ml) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus. PMID- 27558434 TI - Metagenomic and Proteomic Analyses of a Mangrove Microbial Community Following Green Macroalgae Enteromorpha prolifera Degradation. AB - A mangrove microbial community was analyzed at the gene and protein levels using metagenomic and proteomic methods with the green macroalgae Enteromorpha prolifera as the substrate. Total DNA was sequenced on the Illumina HiSeq 2000 PE 100 platform. Two-dimensional gel electrophoresis in combination with liquid chromatography tandem mass spectrometry was used for proteomic analysis. The metagenomic data revealed that the orders Pseudomonadales, Rhizobiales, and Sphingomonadales were the most prevalent in the mangrove microbial community. By monitoring changes at the functional level, proteomic analyses detected ATP synthase and transporter proteins, which were expressed mainly by members of the phyla Proteobacteria and Bacteroidetes. Members of the phylum Proteobacteria expressed a high number of sugar transporters and demonstrated specialized and efficient digestion of various glycans. A few glycoside hydrolases were detected in members of the phylum Firmicutes, which appeared to be the main cellulose degrading bacteria. This is the first report of multiple "omics" analysis of E. prolifera degradation. These results support the fact that key enzymes of glycoside hydrolase family were expressed in large quantities, indicating the high metabolic activity of the community. PMID- 27558435 TI - Spatial Pattern of Copper Phosphate Precipitation Involves in Copper Accumulation and Resistance of Unsaturated Pseudomonas putida CZ1 Biofilm. AB - Bacterial biofilms are spatially structured communities that contain bacterial cells with a wide range of physiological states. The spatial distribution and speciation of copper in unsaturated Pseudomonas putida CZ1 biofilms that accumulated 147.0 mg copper per g dry weight were determined by transmission electron microscopy coupled with energy dispersive X-ray analysis, and micro-X ray fluorescence microscopy coupled with micro-X-ray absorption near edge structure (micro-XANES) analysis. It was found that copper was mainly precipitated in a 75 MUm thick layer as copper phosphate in the middle of the biofilm, while there were two living cell layers in the air-biofilm and biofilm medium interfaces, respectively, distinguished from the copper precipitation layer by two interfaces. The X-ray absorption fine structure analysis of biofilm revealed that species resembling Cu3(PO4)2 predominated in biofilm, followed by Cu-Citrate- and Cu-Glutathione-like species. Further analysis by micro-XANES revealed that 94.4% of copper were Cu3(PO4)2-like species in the layer next to the air interface, whereas the copper species of the layer next to the medium interface were composed by 75.4% Cu3(PO4)2, 10.9% Cu-Citrate-like species, and 11.2% Cu-Glutathione-like species. Thereby, it was suggested that copper was initially acquired by cells in the biofilm-air interface as a citrate complex, and then transported out and bound by out membranes of cells, released from the copper-bound membranes, and finally precipitated with phosphate in the extracellular matrix of the biofilm. These results revealed a clear spatial pattern of copper precipitation in unsaturated biofilm, which was responsible for the high copper tolerance and accumulation of the biofilm. PMID- 27558436 TI - Identification and Functional Analysis of RelA/SpoT Homolog (RSH) Genes in Deinococcus radiodurans. AB - To identify the global effects of (p)ppGpp in the gram-positive bacterium Deinococcus radiodurans, which exhibits remarkable resistance to radiation and other stresses, RelA/SpoT homolog (RSHs) mutants were constructed by direct deletion mutagenesis. The results showed that RelA has both synthesis and hydrolysis domains of (p)ppGpp, whereas RelQ only synthesizes (p)ppGpp in D. radiodurans. The growth assay for mutants and complementation analysis revealed that deletion of relA and relQ sensitized the cells to H2O2, heat shock, and amino acid limitation. Comparative proteomic analysis revealed that the bifunctional RelA is involved in DNA repair, molecular chaperone functions, transcription, the tricarboxylic acid cycle, and metabolism, suggesting that relA maintains the cellular (p)ppGpp levels and plays a crucial role in oxidative resistance in D. radiodurans. The D. radiodurans relA and relQ genes are responsible for (p)ppGpp synthesis/hydrolysis and (p)ppGpp hydrolysis, respectively. (p)ppGpp integrates a general stress response with a targeted re programming of gene regulation to allow bacteria to respond appropriately towards heat shock, oxidative stress, and starvation. This is the first identification of RelA and RelQ involvement in response to oxidative, heat shock, and starvation stresses in D. radiodurans, which further elucidates the remarkable resistance of this bacterium to stresses. PMID- 27558437 TI - Potential Swimming Motility Variation by AcrR in Escherichia coli. AB - AcrR, the toxic-compounds-response regulator, regulates motility in microorganisms, presumably to escape from toxic environments. In this study, the genome-wide target genes of AcrR were investigated in a DeltaacrR mutant strain by microarray analysis. In the absence of AcrR, the transcription of most flagella/motility genes was highly increased. In addition, flagella formation was increased in this mutant strain. Motility assays revealed that AcrR modulates swimming motility, but not swarming. PMID- 27558438 TI - PspAG97A: A Halophilic alpha-Glucoside Hydrolase with Wide Substrate Specificity from Glycoside Hydrolase Family 97. AB - A novel alpha-glucoside hydrolase (named PspAG97A) from glycoside hydrolase family 97 (GH97) was cloned from the deep-sea bacterium Pseudoalteromonas sp. K8, which was screened from the sediment of Kongsfjorden. Sequence analysis showed that PspAG97A belonged to GH97, and shared 41% sequence identity with the characterized alpha-glucosidase BtGH97a. PspAG97A possessed three key catalytically related glutamate residues. Mutation of the glutamate residues indicated that PspAG97A belonged to the inverting subfamily of GH97. PspAG97A showed significant reversibility against changes in salt concentration. It exhibited halophilic ability and improved thermostability in NaCl solution, with maximal activity at 1.0 M NaCl/KCl, and retained more than 80% activity at NaCl concentrations ranging from 0.8 to 2.0 M for over 50 h. Furthermore, PspAG97A hydrolyzed not only alpha-1,4-glucosidic linkage, but also alpha-1,6- and alpha 1,2-glucosidic linkages. Interestingly, PspAG97A possessed high catalytic efficiency for long-chain substrates with alpha-1,6-linkage. These characteristics are clearly different from other known alpha-glucoside hydrolases in GH97, implying that PspAG97A is a unique alpha-glucoside hydrolase of GH97. PMID- 27558439 TI - Biodegradation of Ochratoxin A by Aspergillus tubingensis Isolated from Meju. AB - Ochratoxin A (OTA), a mycotoxin, contaminates agricultural products and poses a serious threat to public health worldwide. Microbiological methods are known to be a promising approach for OTA biodegradation because physical and chemical methods have practical limitations. In the present study, a total of 130 fungal isolates obtained from 65 traditional Korean meju (a fermented starter for fermentation of soybeans) samples were examined for OTA-biodegradation activity using thin-layer chromatography. Two fungal isolates were selected for OTA biodegradation activity and were identified as Aspergillus tubingensis M036 and M074 through sequence analysis of the beta-tubulin gene. After culturing both A. tubingensis isolates in Soytone-Czapek medium containing OTA (40 ng/ml), OTA biodegradation activity was analyzed using high-performance liquid chromatography (HPLC). Both A. tubingensis strains degraded OTA by more than 95.0% after 14 days, and the HPLC analysis showed that the OTA biodegradation by the A. tubingensis strains led to the production of ochratoxin alpha, which is much less toxic than OTA. Moreover, crude enzymes from the cultures of A. tubingensis M036 and M074 led to OTA biodegradation of 97.5% and 91.3% at pH 5, and 80.3% and 75.3% at pH 7, respectively, in a buffer solution containing OTA (40 ng/ml) after 24 h. In addition, the OTA-biodegrading fungi did not exhibit OTA production activity. Our data suggest that A. tubingensis isolates and their enzymes have the potential for practical application to reduce levels of OTA in food and feed. PMID- 27558440 TI - Insertion Mutation in HMG-CoA Lyase Increases the Production Yield of MPA through Agrobacterium tumefaciens-Mediated Transformation. AB - Mycophenolic acid (MPA) is an antibiotic produced by Penicillium brevicompactum. MPA has antifungal, antineoplastic, and immunosuppressive functions, among others. beta-Hydroxy-beta-methylglutaryl-CoA (HMG-CoA) lyase is a key enzyme in the bypass metabolic pathway. The inhibitory activity of HMG-CoA lyase increases the MPA biosynthetic flux by reducing the generation of by-products. In this study, we cloned the P. brevicompactum HMG-CoA lyase gene using the thermal asymmetric interlaced polymerase chain reaction and gene walking technology. Agrobacterium tumefaciens-mediated transformation (ATMT) was used to insert a mutated HMG-CoA lyase gene into P. brevicompactum. Successful insertion of the HMG-CoA lyase gene was confirmed by hygromycin screening, PCR, Southern blot analysis, and enzyme content assay. The maximum MPA production by transformants was 2.94 g/l. This was 71% higher than wild-type ATCC 16024. Our results demonstrate that ATMT may be an alternative practical genetic tool for directional transformation of P. brevicompactum. PMID- 27558441 TI - Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody. AB - Inflammation-triggered combination delivery of anti-PD-1 antibody and CpG oligodeoxynucleotides (CpG ODNs) has been demonstrated to prevent cancer relapse utilizing postsurgical inflammatory response. The controlled release of anti-PD1 and CpG ODN by CpG DNA-based "nano-cocoons" can induce considerable immune response, which in turn significantly prolongs the survival time of mice. PMID- 27558443 TI - Fetal anemia, cerebellar hemorrhage and hypoplasia associated with congenital Parvovirus infection. AB - We report a case of fetal cerebellar hemorrhage and hypoplasia, identified by fetal MRI after intrauterine blood transfusion at 21 weeks' gestation for treatment of severe anemia due to congenital Parvovirus infection. Postnatal MRI confirmed atrophy of bilateral cerebellar hemispheres and inferior vermis. Cerebellar capillaries may be extremely susceptible to hemodynamic changes in the setting of intrauterine blood transfusion due to severe anemia. Although the correlation between fetal intracranial anomalies and Parvovirus infection remains unclear, in this population, a detailed evaluation of the brain parenchyma should be considered prior to and after intrauterine blood transfusion. PMID- 27558442 TI - Fish oil prevents changes induced by a high-fat diet on metabolism and adipokine secretion in mice subcutaneous and visceral adipocytes. AB - KEY POINTS: Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has beneficial effects on changes induced by obesity and partially prevents associated comorbidities. The effects of FO on adipocytes from different adipose tissue depots in high-fat (HF) diet induced obese mice have not been uninvestigated. This is the first study to examine the effects of FO on changes in metabolism and adipokine production in adipocytes from s.c. (inguinal; ING) or visceral (retroperitoneal; RP) white adipose depots in a HF diet-induced obese mice. Unlike most studies performed previously, FO supplementation was initiated 4 weeks before the induction of obesity. HF diet caused marked changes in ING (glucose uptake and secretion of adiponectin, tumour necrosis factor-alpha and interleukin-6 in ING) and RP (lipolysis, de novo lipogenesis and secretion of pro inflammatory cytokines) adipose depots. Previous and concomitant FO administration prevented the changes in ING and RP adipocytes induced by the HF diet. ABSTRACT: In the present study, we investigated the effect of fish oil (FO) on metabolism and adipokine production by adipocytes from s.c. (inguinal; ING) and visceral (retroperitoneal; RP) white adipose depots in high-fat (HF) diet induced obese mice. Mice were divided into CO (control diet), CO+FO, HF and HF+FO groups. The HF group presented higher body weight, glucose intolerance, insulin resistance, higher plasma total and low-density lipoprotein cholesterol levels, and greater weights of ING and RP adipose depots accompanied by hypertrophy of the adipocytes. FO exerted anti-obesogenic effects associated with beneficial effects on dyslipidaemia and insulin resistance in mice fed a HF diet (HF+FO group). HF raised RP adipocyte lipolysis and the production of pro-inflammatory cytokines and reduced de novo synthesis of fatty acids, whereas, in ING adipocytes, it decreased glucose uptake and adiponectin secretion but did not change lipolysis. Therefore, the adipose depots play different roles in HF diet induced insulin resistance according to their location in the body. Concerning cytokine secretion, adipocytes per se in addition to white adopise tissue infiltrated leukocytes have to be considered in the aetiology of the comorbidities associated with obesity. Evidence is presented showing that previous and concomitant administration of FO can prevent changes in metabolism and the secretion of hormones and cytokines in ING and RP adipocytes induced by HF. PMID- 27558444 TI - Evolution of Electronic Circuits using Carbon Nanotube Composites. AB - Evolution-in-materio concerns the computer controlled manipulation of material systems using external stimuli to train or evolve the material to perform a useful function. In this paper we demonstrate the evolution of a disordered composite material, using voltages as the external stimuli, into a form where a simple computational problem can be solved. The material consists of single walled carbon nanotubes suspended in liquid crystal; the nanotubes act as a conductive network, with the liquid crystal providing a host medium to allow the conductive network to reorganise when voltages are applied. We show that the application of electric fields under computer control results in a significant change in the material morphology, favouring the solution to a classification task. PMID- 27558446 TI - Cutaneous manifestations of hepatocellular cancer (HCC). PMID- 27558445 TI - The emergence of superstructural order in insulin amyloid fibrils upon multiple rounds of self-seeding. AB - Typically, elongation of an amyloid fibril entails passing conformational details of the mother seed to daughter generations of fibrils with high fidelity. There are, however, several factors that can potentially prevent such transgenerational structural imprinting from perpetuating, for example heterogeneity of mother seeds or so-called conformational switching. Here, we examine phenotypic persistence of bovine insulin amyloid ([BI]) upon multiple rounds of self-seeding under quiescent conditions. According to infrared spectroscopy, with the following passages of homologous seeding, daughter fibrils gradually depart from the mother seed's spectral characteristics. We note that this transgenerational structural drift in [BI] amyloid leads toward fibrils with infrared, chiroptical, and morphological traits similar to those of the superstructural variant of fibrils which normally forms upon strong agitation of insulin solutions. However, in contrast to agitation-induced insulin amyloid, the superstructural assemblies of daughter fibrils isolated through self-seeding are sonication-resistant. Our results suggest that formation of single amyloid fibrils is not a dead-end of the amyloidogenic self-assembly. Instead, the process appears to continue toward the self-assembly of higher-order structures although on longer time-scales. From this perspective, the fast agitation-induced aggregation of insulin appears to be a shortcut to amyloid superstructures whose formation under quiescent conditions is slow. PMID- 27558447 TI - Selenide-Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes. AB - The efficient regio- and stereoselective construction of tetrasubstituted alkenes is challenging and very important. For this purpose, we have developed an efficient approach to synthesize tetrasubstituted trifluoromethylthiolated alkenes from simple alkynes in excellent regio- and stereoselectivities by selenide-catalyzed multicomponent coupling. Using this method, trifluoromethylthiolated alkenyl triflates and arenes were achieved. In particular, the triflates could be further converted into carbofunctionalized alkenes by palladium-catalyzed cross-coupling reactions. Our method provides a new pathway for the construction of trifluoromethylthiolated tricarboalkenes. This work presents the first example of selenide-catalyzed trifluoromethylthiolation of alkynes and enables the challenging functionalizations of alkynes. PMID- 27558449 TI - Comparison between several techniques of olive tree bark extraction (Tunisian Chemlali variety). AB - In order to better understand the chemical composition of the olive tree bark of Tunisian chemlali variety (Olea europaea cv. 'Chemlali'), this material was extracted by different ways. Compositions of extracts were used at best-selected conditions for each technique, and characterised using HPLC, LC/MS and GC-MS techniques. Analyses are conducted to an important variety of high carbon number compounds such as aliphatic compounds as nanocosane and heptacosane, and molecules with high value added tax (VAT) which can be classified as follows: diterpenes as phytol, triterpenes as squalene and also esters as Benzyl cinnamate. Hydrodistillation at high pressure seems to be a very common method to get a wide variety of compounds, the results are better than the ones obtained using supercritical fluid extraction and solvent extraction. PMID- 27558448 TI - Functional characterization of open chromatin in bidirectional promoters of rice. AB - Bidirectional gene pairs tend to be highly coregulated and function in similar biological processes in eukaryotic genomes. Structural features and functional consequences of bidirectional promoters (BDPs) have received considerable attention among diverse species. However, the underlying mechanisms responsible for the bidirectional transcription and coexpression of BDPs remain poorly understood in plants. In this study, we integrated DNase-seq, RNA-seq, ChIP-seq and MNase-seq data and investigated the effect of physical DNase I hypersensitive site (DHS) positions on the transcription of rice BDPs. We found that the physical position of a DHS relative to the TSS of bidirectional gene pairs can affect the expression of the corresponding genes: the closer a DHS is to the TSS, the higher is the expression level of the genes. Most importantly, we observed that the distribution of DHSs plays a significant role in the regulation of transcription and the coexpression of gene pairs, which are possibly mediated by orchestrating the positioning of histone marks and canonical nucleosomes around BDPs. Our results demonstrate that the combined actions of chromatin structures with DHSs, which contain functional cis-elements for interaction with transcriptional machinery, may play an important role in the regulation of the bidirectional transcription or coexpression in rice BDPs. Our findings may help to enhance the understanding of DHSs in the regulation of bidirectional gene pairs. PMID- 27558450 TI - Performance comparison of ethanol and butanol production in a continuous and closed-circulating fermentation system with membrane bioreactor. AB - Since both ethanol and butanol fermentations are urgently developed processes with the biofuel-demand increasing, performance comparison of aerobic ethanol fermentation and anerobic butanol fermentation in a continuous and closed circulating fermentation (CCCF) system was necessary to achieve their fermentation characteristics and further optimize the fermentation process. Fermentation and pervaporation parameters including the average cell concentration, glucose consumption rate, cumulated production concentration, product flux, and separation factor of ethanol fermentation were 11.45 g/L, 3.70 g/L/h, 655.83 g/L, 378.5 g/m2/h, and 4.83, respectively, the corresponding parameters of butanol fermentation were 2.19 g/L, 0.61 g/L/h, 28.03 g/L, 58.56 g/m2/h, and 10.62, respectively. Profiles of fermentation and pervaporation parameters indicated that the intensity and efficiency of ethanol fermentation was higher than butanol fermentation, but the stability of butanol fermentation was superior to ethanol fermentation. Although the two fermentation processes had different features, the performance indicated the application prospect of both ethanol and butanol production by the CCCF system. PMID- 27558451 TI - Yeast derived from lignocellulosic biomass as a sustainable feed resource for use in aquaculture. AB - The global expansion in aquaculture production implies an emerging need of suitable and sustainable protein sources. Currently, the fish feed industry is dependent on high-quality protein sources of marine and plant origin. Yeast derived from processing of low-value and non-food lignocellulosic biomass is a potential sustainable source of protein in fish diets. Following enzymatic hydrolysis, the hexose and pentose sugars of lignocellulosic substrates and supplementary nutrients can be converted into protein-rich yeast biomass by fermentation. Studies have shown that yeasts such as Saccharomyces cerevisiae, Candida utilis and Kluyveromyces marxianus have favourable amino acid composition and excellent properties as protein sources in diets for fish, including carnivorous species such as Atlantic salmon and rainbow trout. Suitable downstream processing of the biomass to disrupt cell walls is required to secure high nutrient digestibility. A number of studies have shown various immunological and health benefits from feeding fish low levels of yeast and yeast-derived cell wall fractions. This review summarises current literature on the potential of yeast from lignocellulosic biomass as an alternative protein source for the aquaculture industry. It is concluded that further research and development within yeast production can be important to secure the future sustainability and economic viability of intensive aquaculture. (c) 2016 Society of Chemical Industry. PMID- 27558452 TI - A possible four-phase coexistence in a single-component system. AB - For different phases to coexist in equilibrium at constant temperature T and pressure P, the condition of equal chemical potential MU must be satisfied. This condition dictates that, for a single-component system, the maximum number of phases that can coexist is three. Historically this is known as the Gibbs phase rule, and is one of the oldest and venerable rules of thermodynamics. Here we make use of the fact that, by varying model parameters, the Gibbs phase rule can be generalized so that four phases can coexist even in single-component systems. To systematically search for the quadruple point, we use a monoatomic system interacting with a Stillinger-Weber potential with variable tetrahedrality. Our study indicates that the quadruple point provides flexibility in controlling multiple equilibrium phases and may be realized in systems with tunable interactions, which are nowadays feasible in several soft matter systems such as patchy colloids. PMID- 27558453 TI - Promising new strategies for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide. It usually arises based on a background of chronic liver diseases, defined as the hypercarcinogenic state. The current treatment options for HCC ranging from locoregional treatments to chemotherapies, including sorafenib, effectively regulate the limited sizes and numbers of the nodules. However, these treatments remain unsatisfactory because they have insufficient antitumor effects on the large and numerous nodules associated with HCC and because of a high recurrence rate in the surrounding inflamed liver. To develop novel and promising therapies with higher antitumor effects, recent progress in identifying molecular targets and developing immunological procedures for HCC are reviewed. The molecular targets discussed include the intracellular signaling pathways of protein kinase B/mammalian target of rapamycin and RAS/RAF/mitogen-activated protein kinase, Wnt/beta-catenin and glutamine synthetase, insulin-like growth factor, signal transducer and activator of transcription 3, nuclear factor-kappaB and telomerase reverse transcriptase, and c-MET. Immunological studies have focused mainly on target identification, T cells, natural killer cells, dendritic cells, natural killer T cells, and vaccine development. PMID- 27558454 TI - Design and development of pH-responsive HSPC:C12H25-PAA chimeric liposomes. AB - The application of stimuli-responsive medical practices has emerged, in which pH sensitive liposomes figure prominently. This study investigates the impact of the incorporation of different amounts of pH-sensitive polymer, C12H25-PAA (poly(acrylic acid) with a hydrophobic end group) in l-alpha-phosphatidylcholine, hydrogenated (Soy) (HSPC) phospholipidic bilayers, with respect to biomimicry and functionality. PAA is a poly(carboxylic acid) molecule, classified as a pH sensitive polymer, whose pH-sensitivity is attributed to its regulative -COOH groups, which are protonated under acidic pH (pKa ~4.2). Our concern was to fully characterize, in a biophysical and thermodynamical manner, the mixed nanoassemblies arising from the combination of the two biomaterials. At first, we quantified the physicochemical characteristics and physical stability of the prepared chimeric nanosystems. Then, we studied their thermotropic behavior, through measurement of thermodynamical parameters, using Differential Scanning Calorimetry (DSC). Finally, the loading and release of indomethacin (IND) were evaluated, as well as the physicochemical properties and stability of the nanocarriers incorporating it. As expected, thermodynamical findings are in line with physicochemical results and also explain the loading and release profiles of IND. The novelty of this investigation is the utilization of these pH-sensitive chimeric advanced Drug Delivery nano Systems (aDDnSs) in targeted drug delivery which relies entirely on the biophysics and thermodynamics between such designs and the physiological membranes and environment of living organisms. PMID- 27558456 TI - BMDREDD REGULATES THE APOPTOSIS COORDINATING WITH BMDAXX, BMCIDE-B, BMFADD, AND BMCREB IN BMN CELLS. AB - The apoptosis mechanisms in mammals were investigated relatively clearly. However, little is known about how apoptosis is achieved at a molecular level in silkworm cells. We cloned a caspase homologous gene named BmDredd (where Bm is Bombyx mori and Dredd is death-related ced-3/Nedd2-like caspase) in BmN cells from the ovary of Bm and analyzed its biological information. We constructed the N-terminal, C-terminal, and overexpression vector of BmDredd, respectively. Our results showed that the transcriptional expression level of BmDredd was increased in the apoptotic BmN cells. Furthermore, overexpression of BmDredd increased the caspase-3/7 activity. Simultaneously, RNAi of BmDredd could save BmN cells from apoptosis. The immunofluorescence study showed that BmDredd located at the cytoplasm in normal cell otherwise is found at the nucleus when cells undergo apoptosis. Moreover, we quantified the transcriptional expressions of apoptosis related genes including BmDredd, BmDaxx (where Daxx is death-domain associated protein), BmCide-b (where Cide-b is cell death inducing DFF45-like effector), BmFadd (Fadd is fas-associated via death domain), and BmCreb (where Creb is cAMP response element binding protein) in BmN cells with dsRNA interferences to detect the molecular mechanism of apoptosis. In conclusion, BmDredd may function for promoting apoptosis and there are various regulatory interactions among these apoptosis-related genes. PMID- 27558457 TI - Optimal anthropometric measures and thresholds to identify undiagnosed type 2 diabetes in three major Asian ethnic groups. AB - OBJECTIVE: To identify optimal anthropometric measures and cutoffs to identify undiagnosed diabetes mellitus (UDM) in three major Asian ethnic groups (Chinese, Malays, and Asian-Indians). METHODS: Cross-sectional data were analyzed from 14,815 ethnic Chinese, Malay, and Asian-Indian participants of the Singapore National Health Surveys, which included anthropometric measures and an oral glucose tolerance test. Receiver operating characteristic curve analyses were used with calculation of the area under the curve (AUC) to evaluate the performance of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) for the identification of UDM. RESULTS: BMI performed significantly worse (AUCMEN = 0.70; AUCWOMEN = 0.75) than abdominal measures, whereas WHTR (AUCMEN = 0.76; AUCWOMEN = 0.79) was among the best performing measures in both sexes and all ethnic groups. Anthropometric measures performed better in Chinese than in Asian-Indian participants for the identification of UDM. A WHTR cutoff of 0.52 appeared optimal with a sensitivity of 76% in men and 73% in women and a specificity of 63% in men and 70% in women. CONCLUSIONS: Although ethnic differences were observed in the performance of anthropometric measures for the identification of UDM, abdominal adiposity measures generally performed better than BMI, and WHTR performed best in all Asian ethnic groups. PMID- 27558455 TI - Inactivation of TGFbeta receptors in stem cells drives cutaneous squamous cell carcinoma. AB - Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFbeta Smad signalling, which is localized to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through Braf(V600E) or Kras(G12D) knockin) and TGFbeta signalling ablation (through Tgfbr1 deletion) in LGR5(+ve) stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5(+ve) cells also results in cSCC development. These findings indicate that LGR5(+ve) stem cells may act as cells of origin for cSCC, and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFbeta signalling, are driving events of skin tumorigenesis. PMID- 27558459 TI - The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women. AB - OBJECTIVES: To assess the effect of microablative fractional CO2 laser (MFCO2 Laser) therapy on the vaginal microenvironment of postmenopausal women. METHODS: Three laser therapies at monthly intervals were applied in postmenopausal women with moderate to severe symptoms of genitourinary syndrome of menopause, pH of vaginal fluid >4.5 and superficial epithelial cells on vaginal smear <5%. Vaginal fluid pH values, fresh wet mount microscopy, Gram stain and aerobic and anaerobic cultures were evaluated at baseline and 1 month after each subsequent therapy. Nugent score and Hay-Ison criteria were used to evaluate vaginal flora. RESULTS: Fifty-three women (mean age 57.2 +/- 5.4 years) participated and completed this study. MFCO2-Laser therapy increased Lactobacillus (p < 0.001) and normal flora (p < 0.001) after the completion of the therapeutic protocol, which decreased vaginal pH from a mean of 5.5 +/- 0.8 (initial value) to 4.7 +/- 0.5 (p < 0.001). The prevalence of Lactobacillus changed from 30% initially to 79% after the last treatment. Clinical signs and symptoms of bacterial vaginosis, aerobic vaginitis or candidiasis did not appear in any participant. CONCLUSION: MFCO2-Laser therapy is a promising treatment for improving the vaginal health of postmenopausal women by helping repopulate the vagina with normally existing Lactobacillus species and reconstituting the normal flora to premenopausal status. PMID- 27558458 TI - Comparison of intraspecific, interspecific and intergeneric chloroplast diversity in Cycads. AB - Cycads are among the most threatened plant species. Increasing the availability of genomic information by adding whole chloroplast data is a fundamental step in supporting phylogenetic studies and conservation efforts. Here, we assemble a dataset encompassing three taxonomic levels in cycads, including ten genera, three species in the genus Cycas and two individuals of C. debaoensis. Repeated sequences, SSRs and variations of the chloroplast were analyzed at the intraspecific, interspecific and intergeneric scale, and using our sequence data, we reconstruct a phylogenomic tree for cycads. The chloroplast was 162,094 bp in length, with 133 genes annotated, including 87 protein-coding, 37 tRNA and 8 rRNA genes. We found 7 repeated sequences and 39 SSRs. Seven loci showed promising levels of variations for application in DNA-barcoding. The chloroplast phylogeny confirmed the division of Cycadales in two suborders, each of them being monophyletic, revealing a contradiction with the current family circumscription and its evolution. Finally, 10 intraspecific SNPs were found. Our results showed that despite the extremely restricted distribution range of C. debaoensis, using complete chloroplast data is useful not only in intraspecific studies, but also to improve our understanding of cycad evolution and in defining conservation strategies for this emblematic group. PMID- 27558460 TI - Ultrathin Molecular-Layer-by-Layer Polyamide Membranes: Insights from Atomistic Molecular Simulations. AB - In this study, we present an atomistic simulation study of several physicochemical properties of polyamide (PA) membranes formed from interfacial polymerization or from a molecular-layer-by-layer (mLbL) on a silicon wafer. These membranes are composed of meta-phenylenediamine (MPD) and benzene-1,3,5 tricarboxylic acid chloride (TMC) for potential reverse osmosis (RO) applications. The mLbL membrane generation procedure and the force field models were validated, by comparison with available experimental data, for hydrated density, membrane swelling, and pore size distributions of PA membranes formed by interfacial polymerization. Physicochemical properties such as density, free volume, thickness, the degree of cross-linking, atomic compositions, and average molecular orientation (which is relevant for the mLbL membranes) are compared for these different processes. The mLbL membranes are investigated systematically with respect to TMC monomer growth rate per substrate surface area, MPD/TMC ratio, and the number of mLbL deposition cycles. Atomistic simulations show that the mLbL deposition generates membranes with a constant film growth if both the TMC monomer growth rate and MPD/TMC monomer ratio are kept constant. The film growth rate increases with TMC monomer growth rate or MPD/TMC ratio. Furthermore, it was found on one hand that the mLbL membrane density and free volume varies significantly with respect to the TMC monomer growth rate, while on the other hand the degree of cross-linking and the atomic composition varies considerably with the MPD/TMC ratio. Additionally, it was found that both TMC and MPD orient at a tilted angle with respect to the substrate surface, where their angular distribution and average angle orientation depend on both the TMC growth rate and the number of deposition cycles. This study illustrates that molecular simulations can play a crucial role in the understanding of structural properties that can empower the design of the next generation RO membranes created from molecular-layer-by-layer (mLbL) on a silicon wafer. PMID- 27558461 TI - Comparison of Transradial vs Transfemoral Access for Aortoiliac and Femoropopliteal Interventions: A Single-Center Experience. AB - PURPOSE: To compare the procedure and safety outcomes of the transradial approach (TRA) with the femoral approach (FA) for treating aortoiliac and femoropopliteal stenoses and occlusions. METHODS: A single-center retrospective study was conducted involving 188 patients (mean age 66.4+/-10.8 years; 116 men) with lower limb claudication or critical limb ischemia who underwent aortoiliac (131, 62.4%) or femoropopliteal (79, 37.6%) interventions on 210 lesions over a 3-year period. Operator discretion determined TRA suitability; exclusions included Raynaud's disease, upper limb occlusive disease, previous TRA difficulties, or planned hemodialysis. Lesion characteristics, clinical endpoints, and access site complications were compared. RESULTS: FA was used primarily in 123 patients and the TRA (12 left and 53 right radial arteries) in 65 procedures. Eleven (16.9%) TRAs failed vs 9 (7.3%) FAs (p=0.42). Crossover to FA was due to occlusive lesions requiring alternative equipment in 9 cases and to tortuosity of the aortic arch vessels in 2 patients. The 134 FA interventions (balloon angioplasty, stents) were retrograde (112, 83.6%) or antegrade (22, 16.4%). There were significantly more TASC C/D lesions in the FA group (p=0.02). Sheath sizes (5-F to 8-F) did not differ between groups, and no significant differences were found between FA vs TRA in terms of procedure time (50.0+/-28.9 vs 46.8+/-25.1 minutes, p=0.50) or length of stay (2.2+/-0.6 vs 2.1+/-0.3 days, p=0.24). While there were no strokes, access site complications occurred in 6.0% of the FA patients vs 3.7% of the TRA patients (p=0.12). CONCLUSION: The transradial approach for aortoiliac and femoropopliteal interventions is safe and efficacious compared with the transfemoral approach for a range of lesion subtypes. Nevertheless, there remains a need for improvements in peripheral device and catheter technology to decrease transradial failure rates. PMID- 27558462 TI - Commentary: Alternative Approach to Successful Crossing: The Retrograde Tibiopedal Technique. PMID- 27558464 TI - Unfolded protein response is activated in the ipsilateral thalamus following focal cerebral infarction in hypertensive rats. AB - Focal cerebral cortical infarction causes secondary neurodegeneration in the remote regions, such as the ventroposterior nucleus of the thalamus. Retrograde degeneration of thalamocortical fibers is considered as the principle mechanism, but the exact molecular events remain to be elucidated. This study aimed to investigate whether unfolded protein response (UPR) is activated in thalamic neurons following distal middle cerebral artery occlusion (MCAO) in stroke-prone renovascular hypertensive rats. Immunostaining and immunoblotting were performed to evaluate the expression of Grp78 and its downstream effectors in the thalamus at 3, 7 and 14 days after MCAO. Secondary thalamic degeneration was assessed with Nissl staining and NeuN immunostaining. Neuronal death was not apparent at 3 days post-ischaemia but was evident in the thalamus at 7 and 14 days after MCAO. Grp78 level was reduced in the ipsilateral thalamus at 3 and 7 days after MCAO. In parallel, phosphorylated eIF2alpha and ATF4 levels were elevated, indicating the activation of UPR. In contrast, ATF6alpha and CHOP levels were not changed. These results suggest that UPR is activated before neuronal death in the ipsilateral thalamus after MCAO and may represent a key early event in the secondary thalamic degeneration. PMID- 27558463 TI - Tibiopedal Access for Crossing of Infrainguinal Artery Occlusions: A Prospective Multicenter Observational Study. AB - PURPOSE: To report a prospective, multicenter, observational study (ClinicalTrials.gov identifier NCT01609621) of the safety and effectiveness of tibiopedal access and retrograde crossing in the treatment of infrainguinal chronic total occlusions (CTOs). METHODS: Twelve sites around the world prospectively enrolled 197 patients (mean age 71+/-11 years, range 41-93; 129 men) from May 2012 to July 2013 who met the inclusion criterion of at least one CTO for which a retrograde crossing procedure was planned or became necessary. The population consisted of 64 (32.5%) claudicants (Rutherford categories 2/3) and 133 (67.5%) patients with critical limb ischemia (Rutherford category >=4). A primary antegrade attempt to cross had been made prior to the tibiopedal attempt in 132 (67.0%) cases. Techniques used for access, retrograde lesion crossing, and treatment were at the operator's discretion. Follow-up data were obtained 30 days after the procedure. RESULTS: Technical tibiopedal access success was achieved in 184 (93.4%) of 197 patients and technical occlusion crossing success in 157 (85.3%) of the 184 successful tibial accesses. Failed access attempts were more common in women (9 of 13 failures). The rate of successful crossing was roughly equivalent between sexes [84.7% (50/59) women compared to 85.6% (107/125) men]. Technical success did not differ significantly based on a prior failed antegrade attempt: the access success rate was 92.4% (122/132) after a failed antegrade access vs 95.4% (62/65) in those with a primary tibiopedal attempt (p=0.55). Similarly, crossing success was achieved in 82.8% (101/122) after a failed antegrade access vs 90.3% (56/62) for patients with no prior antegrade attempt (p=0.19). Minor complications related to the access site occurred in 11 (5.6%) cases; no patient had access vessel thrombosis, compartment syndrome, or surgical revascularization. CONCLUSION: Tibiopedal access appears to be safe and can be used effectively for the crossing of infrainguinal lesions in patients with severe lower limb ischemia. PMID- 27558465 TI - Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection. AB - Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25high CD134+CD39-) and T-regulatory (CD4+CD25high CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-gamma, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine. PMID- 27558466 TI - Alternative Fuel Implementation in a Cement Plant: Human Health Risks and Economical Valuation. AB - In June 2010, the cement plant of Montcada i Reixac (MR) (Catalonia, Spain) began a gradual implementation of alternative fuel to replace fossil fuel. Between December 2010 and November 2014, we conducted three monitoring surveys to evaluate the state of the environment around the facility. Data were compared with results from three monitoring surveys performed in 2008-2009. In all these studies, samples of soil, vegetation, and air were collected, being the content of a number of trace elements and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in these matrices determined. In general terms, a decrease of metal and PCDD/F concentrations was found. Human health risks followed a similar temporal trend, being acceptable according to national and international standards and independent on the fuel used. The Disability-Adjusted Life Year and the costs of cancer cases were also estimated for the population living around the MR cement plant, accounting for 4 years and 31,000 ?/year, respectively. PMID- 27558468 TI - Dilemmas in management of suspected venous thromboembolism in the obese patient. PMID- 27558467 TI - Predictors of relapse and long-term outcome in children with steroid-dependent nephrotic syndrome after rituximab treatment. AB - BACKGROUND: In patients with complicated steroid-dependent nephrotic syndrome (SDNS), rituximab (RTX) followed by immunosuppressive agent (IS) can maintain remission without the use of prednisolone (PSL). However, available data on the predictive factors for relapse and the long-term outcome after this protocol are few. METHODS: We retrospectively analyzed 43 SDNS patients who were followed-up for a long time (>2 years, mean 5.4 years) after a single dose of RTX (375 mg/m2) from September 2007. After RTX, PSL was tapered off within 6 months; monotherapy with IS, such as cyclosporine or mycophenolate mofetil, was continued to prevent post-RTX relapse. For patients who achieved >12 months of PSL-free remission, IS was also tapered off. RESULTS: Thirty-nine patients (91 %) could discontinue PSL without relapses at a median of 154 days after the initial RTX. The first relapse of NS occurred in 39 patients (91 %) at a median of 586 days; additional RTX doses were administered in 28 patients (65 %). Kaplan-Meier analysis showed that shorter CD19 cell depletion (<150 days) and younger age at RTX initiation (<12.5 years) were significantly associated with high risk for first relapse after RTX (log rank p < 0.05). In multivariate analysis, mycophenolate mofetil therapy as maintenance IS after RTX was the only predicted risk factor for first relapse (hazard ratio 2.75; p = 0.027). At the last follow-up, IS was still used in 33 patients (77 %); treatment-free remission (>12 months) was achieved in only five patients (12 %). CONCLUSIONS: The introduction of RTX may not be necessarily associated with improved long-term outcome. PMID- 27558469 TI - Analysis of codon usage bias of envelope glycoprotein genes in nuclear polyhedrosis virus (NPV) and its relation to evolution. AB - BACKGROUND: Analysis of codon usage bias is an extremely versatile method using in furthering understanding of the genetic and evolutionary paths of species. Codon usage bias of envelope glycoprotein genes in nuclear polyhedrosis virus (NPV) has remained largely unexplored at present. Hence, the codon usage bias of NPV envelope glycoprotein was analyzed here to reveal the genetic and evolutionary relationships between different viral species in baculovirus genus. RESULTS: A total of 9236 codons from 18 different species of NPV of the baculovirus genera were used to perform this analysis. Glycoprotein of NPV exhibits weaker codon usage bias. Neutrality plot analysis and correlation analysis of effective number of codons (ENC) values indicate that natural selection is the main factor influencing codon usage bias, and that the impact of mutation pressure is relatively smaller. Another cluster analysis shows that the kinship or evolutionary relationships of these viral species can be divided into two broad categories despite all of these 18 species are from the same baculovirus genus. CONCLUSIONS: There are many elements that can affect codon bias, such as the composition of amino acids, mutation pressure, natural selection, gene expression level, and etc. In the meantime, cluster analysis also illustrates that codon usage bias of virus envelope glycoprotein can serve as an effective means of evolutionary classification in baculovirus genus. PMID- 27558470 TI - Reference Intervals of and Relationships among Essential Trace Elements in Whole Blood of Children Aged 0-14 years. AB - BACKGROUND: Essential trace elements are vital to human health. In this study, our aim was to establish reference intervals of and to evaluate relationships among Ca, Fe, Cu, Mg, and Zn for children. METHODS: We collected blood samples of 3210 children aged 0-14 years from Lu'an, China, and concentrations of the above elements were determined by atomizer absorption spectrophotometer. A nonparametric method was used to establish the reference intervals. RESULTS: Gender-related differences in concentrations were not statistically significant for the elements, except for Fe. There were strong positive and negative correlations between age and Fe (R = 0.305, P < 0.001), Zn (R = 0.573, P < 0.001); and age and Ca (R = -0.372, P < 0.001), Cu (R = -0.127, P < 0.001), respectively. Correlations between Ca-Mg (r = 0.222~0.384, P < 0.001), Fe-Mg (r = 0.495~0.614, P < 0.001), and Fe-Zn (r = 0.239~0.471, P < 0.001) were the strongest compared with others. In multivariable linear regression, after adjusted for confounding factors, the associations between Zn-Fe and Mg-Fe were the strongest with per concentration quintile increase of Fe caused Zn and Mg increasing by 4.19% (beta = 0.041; 95% CI: 0.037, 0.045; P < 0.001) and 3.87% (beta = 0.038; 95% CI: 0.036, 0.040; P < 0.001), respectively. CONCLUSIONS: Gender- and age-based reference intervals of Ca, Fe, Cu, Mg, and Zn for children were established, and correlations between them were quite complex. More works are needed to illuminate these relationships and their impacts on children's health. PMID- 27558471 TI - Entropically Driven Self-Assembly of Bolaamphiphilic Perylene Dyes in Water. AB - The specific hydrophobic effect involved in the self-assembly of a bolaamphiphilic perylene bisimide (PBI) dye bearing oligoethylene glycol (OEG) chains has been identified. In pure water, the self-assembly is entropically driven and enthalpically disfavored, as explored by optical spectroscopy and isothermal titration calorimetry studies. Besides strong pi-pi interactions between the PBI units that are primarily of enthalpic nature, the major contribution to the self-assembly is the gain of entropy by release of confined water molecules from the hydration shell of the hydrophilic OEG moieties. Both contributions favor self-assembly, but their countervailing thermodynamic parameters are reflected in an uncommon temperature dependence, which can be inverted upon gradual addition of an organic cosolvent that makes the pi-pi interaction increasingly dominant. PMID- 27558472 TI - The mental health and wellbeing of first generation migrants: a systematic narrative review of reviews. AB - BACKGROUND: First generation migrants are reportedly at higher risk of mental ill health compared to the settled population. This paper systematically reviews and synthesizes all reviews on the mental health of first generation migrants in order to appraise the risk factors for, and explain differences in, the mental health of this population. METHODS: Scientific databases were searched for systematic reviews (inception-November 2015) which provided quantitative data on the mental ill-health of first generation migrants and associated risk factors. Two reviewers screened titles, abstracts and full text papers for their suitability against pre-specified criteria, methodological quality was assessed. RESULTS: One thousand eight hundred twenty articles were identified, eight met inclusion criteria, which were all moderate or low quality. Depression was mostly higher in first generation migrants in general, and in refugees/asylum seekers when analysed separately. However, for both groups there was wide variation in prevalence rates, from 5 to 44 % compared with prevalence rates of 8-12 % in the general population. Post-Traumatic Stress Disorder prevalence was higher for both first generation migrants in general and for refugees/asylum seekers compared with the settled majority. Post-Traumatic Stress Disorder prevalence in first generation migrants in general and refugees/ asylum seekers ranged from 9 to 36 % compared with reported prevalence rates of 1-2 % in the general population. Few studies presented anxiety prevalence rates in first generation migrants and there was wide variation in those that did. Prevalence ranged from 4 to 40 % compared with reported prevalence of 5 % in the general population. Two reviews assessed the psychotic disorder risk, reporting this was two to three times more likely in adult first generation migrants. However, one review on the risk of schizophrenia in refugees reported similar prevalence rates (2 %) to estimates of prevalence among the settled majority (3 %). Risk factors for mental ill-health included low Gross National Product in the host country, downward social mobility, country of origin, and host country. CONCLUSION: First generation migrants may be at increased risk of mental illness and public health policy must account for this and influencing factors. High quality research in the area is urgently needed as is the use of culturally specific validated measurement tools for assessing migrant mental health. PMID- 27558473 TI - Surgical outcome in pediatric patients with Ebstein's anomaly: A multicenter, long-term study. AB - OBJECTIVE: Surgical outcomes of pediatric patients with Ebstein's anomaly are often described as part of all-age-inclusive series. Our objective is to focus on patients treated surgically in childhood (0-18 y). We study the intended treatment (biventricular or 1.5 ventricle repair or univentricular palliation), freedom from unplanned reoperation and survival of this specific age group, in a nationwide study. DESIGN: Records of all Ebstein's anomaly patients born between 1980 and 2013 were reviewed. Demographic variables, intraoperative procedures and postoperative outcomes were analyzed. RESULTS: Sixty-three patients underwent 109 operations. Median follow-up after diagnosis was 121 months (range 0-216 months). Twenty-nine (46%) patients required surgery in the first year of life, including 21 who required neonatal surgery. The intended treatment was biventricular (n = 37, 59%) and 1.5 ventricle (n = 5, 8%) repair or univentricular (n = 21, 33%) palliation. The one-, five-, and 10-year freedom from unplanned reoperation was 89%, 79%, and 75% respectively. There were nine (14%) in hospital deaths (within 30 d after surgery). Causes of death were low cardiac output syndrome, cardiac failure, hypoxemia, pulmonary hypertension or an unknown cause. There were no late deaths. CONCLUSIONS: Surgery in childhood represents the worse spectrum of disease, biventricular repair is often not applied. Patients often face revision surgery. Mortality is limited to the immediate postsurgical period. PMID- 27558474 TI - Association between anxiety and depression symptoms with resistant hypertension and central hemodynamics: A pilot study. PMID- 27558475 TI - Efficacy of Cancer Care Communication Between Clinicians and Latino Patients in a Rural US-Mexico Border Region: a Qualitative Study of Barriers and Facilitators to Better Communication. AB - Quality of clinician-patient cancer communication is vital to cancer care and survivorship. Racial/ethnic minority patients in rural regions may have unique characteristics including cultural beliefs, language barriers, and low health literacy which require effective cross-cultural cancer communication. Despite the growing US population of racial/ethnic minorities and widespread emphasis on culturally appropriate health communication, little is known about challenges and facilitators of cancer communication among underserved rural Latino cancer patients in the US-Mexico border region. This study conducted secondary data analysis of interview data collected from 22 individual cancer patients living on the US side of the US-Mexico border. Thematic analysis was conducted to explore a priori questions regarding patient experiences with cancer care communication with their providers. Emerging themes included lack of language concordance, patient perspectives on clarity and accuracy of information provided, patient perceptions on provider sensitivity in giving cancer diagnosis, and improving the clinical interpersonal relationship. Practice guidelines are suggested and discussed. These findings illuminate the importance of advancing improvement of cancer communication between clinicians and Spanish language-dominant Latinos. PMID- 27558476 TI - The Polymorphism rs3024505 (C/T) Downstream of the IL10 Gene Is Associated with Crohn's Disease in Serbian Patients with Inflammatory Bowel Disease. AB - Inflammatory bowel disease (IBD), manifesting as Crohn's disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD. PMID- 27558477 TI - Maternal Nutritional Imbalance between Linoleic Acid and Alpha-Linolenic Acid Increases Offspring's Anxious Behavior with a Sex-Dependent Manner in Mice. AB - Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients for normal brain development. The principal dietary n-6 and n-3 PUFAs are linoleic acid (LA) and alpha-linolenic acid (ALA), respectively, We have previously shown that maternal dietary imbalance between these PUFAs, i.e., rich in LA and poor in ALA, affected brain development and increased anxiety-related behavior in the mouse offspring. Here we further addressed sex difference in anxiety-related behavior in the offspring exposed to maternal LA:ALA imbalance. We fed pregnant mice a LA excess/ALA deficient (LA(ex)/ALA(def)) diet, and raised their offspring on a well-balanced LA:ALA diet from an early lactation period. When the offspring were grown to adulthood, they were subjected to behavioral and biochemical analyses. We found that both male and female offspring exposed to the LA(ex)/ALA(def) diet showed increased anxiety-related behavior compared to those exposed to the control diet, which was differently observed between the sexes. The female offspring also exhibited hyperactivity by maternal intake of the LA(ex)/ALA(def) diet. On the other hand, abnormal depressive behavior was undetected in both sexes. We also found that the ratio of n-6 to n-3 PUFAs in the brain was unaffected regardless of maternal diet or offspring's sex. Since the n 6/n-3 ratio is known to influence emotional behavior, it is reasonable to assume that LA:ALA imbalance exposed during brain development is the key for causing enhanced anxiety in adulthood. The present study indicates that maternal dietary imbalance between LA and ALA increases offspring's anxiety-related behavior with a sex-dependent manner. PMID- 27558478 TI - Decellularized matrices as in vitro models of extracellular matrix in tumor tissues at different malignant levels: Mechanism of 5-fluorouracil resistance in colorectal tumor cells. AB - Chemoresistance is a major barrier for tumor chemotherapy. It is well-known that chemoresistance increases with tumor progression. Chemoresistance is altered by both genetic mutations and the alteration of extracellular microenvironment. Particularly, the extracellular matrix (ECM) is remodeled during tumor progression. Therefore, ECM remodeling is expected to cause the acquisition of chemoresistance in highly malignant tumor tissue. Here, we prepared cultured cell derived decellularized matrices that mimic native ECM in tumor tissues at different stages of malignancy, and 5-fluorouracil (5-FU) resistance was compared among these matrices. 5-FU resistance of colorectal tumor cells increased on the matrices derived from highly malignant tumor HT-29 cells, although the resistance did not increase on the matrices derived from low malignant tumor SW480 cells and normal CCD-841-CoN cells. The resistance on HT-29 cell-derived matrices increased through the activation of Akt and the upregulation of ABCB1 and ABCC1 without cell growth promotion, suggesting that ECM remodeling plays important roles in the acquisition of chemoresistance during tumor progression. It is expected that our decellularized matrices, or "staged tumorigenesis-mimicking matrices", will become preferred cell culture substrates for in vitro analysis of comprehensive ECM roles in chemoresistance and the screening and pharmacokinetic analysis of anti-cancer drugs. PMID- 27558479 TI - Hypomineralized Second Primary Molars as Predictor of Molar Incisor Hypomineralization. AB - Molar incisor hypomineralization (MIH) is a developmental defect of dental enamel that shares features with hypomineralized second primary molars (HSPM). Prior to permanent tooth eruption, second primary molars could have predictive value for permanent molar and incisor hypomineralization. To assess this possible relationship, a cross-sectional study was conducted in a sample of 414 children aged 8 and 9 years from the INMA cohort in Valencia (Spain). A calibrated examiner (linear-weighted Kappa 0.83) performed the intraoral examinations at the University of Valencia between November 2013 and 2014, applying the diagnostic criteria for MIH and HSPM adopted by the European Academy of Paediatric Dentistry. 100 children (24.2%) presented MIH and 60 (14.5%) presented HSPM. Co occurrence of the two defects was observed in 11.1% of the children examined. The positive predictive value was 76.7% (63.9-86.6) and the negative predictive value 84.7% (80.6-88.3). The positive likelihood ratio (S/1-E) was 10.3 (5.9-17.9) and the negative likelihood ratio (1-S/E) 0.57 (0.47-0.68). The odds ratio was 18.2 (9.39-35.48). It was concluded that while the presence of HSPM can be considered a predictor of MIH, indicating the need for monitoring and control, the absence of this defect in primary dentition does not rule out the appearance of MIH. PMID- 27558480 TI - A conserved role of the RSC chromatin remodeler in the establishment of nucleosome-depleted regions. AB - The occupancy of nucleosomes governs access to the eukaryotic genomes and results from a combination of biophysical features and the effect of ATP-dependent remodelling complexes. Most promoter regions show a conserved pattern characterized by a nucleosome-depleted region (NDR) flanked by nucleosomal arrays. The conserved RSC remodeler was reported to be critical to establish NDR in vivo in budding yeast but other evidences suggested that this activity may not be conserved in fission yeast. By reanalysing and expanding previously published data, we propose that NDR formation requires, at least partially, RSC in both yeast species. We also discuss the most prominent biological role of RSC and the possibility that non-essential subunits do not define alternate versions of the complex. PMID- 27558482 TI - Benign scrotal masses in children - some new lessons learned. AB - INTRODUCTION: A preponderance of benign intratesticular masses in pre-pubertal males encourages testicular-sparing surgery (TSS). OBJECTIVE: To review outcome of benign testicular lumps in children managed at a tertiary pediatric center more than 7.5years. METHODS: A retrospective review of pediatric benign testicular lesions from January 2008 to June 2015 was performed. RESULTS: There were twelve benign intratesticular tumors. Of these, 11 were in pre-pubertal males; comprising four teratomas, two epidermoid cysts, one dermoid cyst, two cases of Leydig cell hyperplasia, one cystic dysplasia of the rete testis and one large simple intratesticular cyst. We illustrate a case of Leydig cell hyperplasia presenting with precocious puberty limited to the ipsilateral hemi scrotum. TSS was attempted in all 11 pre-pubertal cases, but successfully performed in seven. TSS was possible for a large testicular cyst seemingly replacing the entire testis, with evidence that the testis reconstituted itself after surgery. Recurrence of an epidermoid cysts reported. CONCLUSION: For the first time in the literature, this series reports Leydig cell hyperplasia presenting with ipsilateral hemi-scrotal changes of precocious puberty; shows evidence that the testis reconstitutes itself after TSS for a large cyst; and reports recurrence of an epidermoid cyst after TSS. PMID- 27558481 TI - Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients. AB - INTRODUCTION: Colorectal cancer (CRC) diagnosed before age 30 years is a fatal disease whose biology remains poorly understood. To understand its pathogenesis, we compared molecular and clinical data in surgically treated early-age onset and adult onset patients. MATERIALS AND METHODS: Clinical data and tumor tissue were collected retrospectively for 94 patients with early-age onset CRC (age <=30 years) and compared to 275 adult CRC patients (age >=50 years). Tumor morphology, microsatellite instability (MSI) and stability (MSS), KRAS and BRAF mutations, and mismatch repair (MMR) expression (MSH2, MLH1, MSH6, PMS2) were assessed. RESULTS: Early-age CRC was distinguished from adult CRC by advanced stage presentation (P<0.001), frequent high grade cancers (P<0.001), and poor prognosis (P<0.001). MSI was associated with favorable survival and MMR loss in both groups. Compared to adults, MSI in early-onset CRC was more prevalent (P<0.01), not tightly linked to MLH1/PMS2 loss, and never associated with BRAFV600E mutations (P<0.01). MSS/BRAFV600E genotype had poor prognosis and was more prevalent in early-age CRC (9% vs. 3%). DISCUSSION: Specific genetic subtypes are found at different frequencies in early-age onset and adult onset CRC. Complete absence of the indolent MSI/BRAFV600E genotype and enrichment in the unfavorable MSS/BRAFV600E genotype help explain the poor prognosis of early onset CRC. PMID- 27558483 TI - Distinctive distribution of brain volume reductions in MELAS and mitochondrial DNA A3243G mutation carriers: A voxel-based morphometric study. AB - OBJECTIVE: The aim of this study was to investigate the clinically latent brain atrophy of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) harboring a mitochondrial DNA A3243G mutation (A3243G) and A3243G carriers without stroke-like episodes (SEs). METHODS: We used voxel-based morphometry (VBM) with magnetic resonance imaging to investigate gray matter (GM) and white matter (WM) volume reductions in four MELAS patients and in five A3243G carriers compared to 16 healthy controls. In addition, we investigated the regions of previous SEs using conventional MRI. RESULTS: All four MELAS patients showed significant GM volume reductions in the left superior parietal lobule (SPL), right precuneus, right middle temporal gyrus (MTG), and bilateral posterior lobes of the cerebellum. These areas of GM volume reduction were beyond the regions of previous SEs. As for A3243G carriers, GM volume reductions in the left SPL, right precuneus, right MTG, and bilateral posterior lobes of the cerebellum were detected in three, one, two, and five subjects, respectively. All four MELAS patients showed significant WM volume reductions in the bilateral or unilateral temporal sub-gyral regions, which were included in the regions of previous SEs. No A3243G carriers showed WM volume reductions. CONCLUSION: The distribution patterns of GM volume reductions in VBM may reflect a common vulnerability of the brains among MELAS patients and A3243G carriers. PMID- 27558485 TI - Book ReviewReviews. AB - Larry D. Rosen, Nancy A. Cheever and L. Mark Carrier (Eds.) The Wiley Handbook of Psychology, Technology, and Society John Wiley & Sons Ltd., Chichester, UK, 2015, 1st ed., 592 pp. Hardback ISBN: 978-1-118-77202-7. PMID- 27558484 TI - Recombinant Human Thyrotropin Improves Endothelial Coronary Flow Reserve in Thyroidectomized Patients with Differentiated Thyroid Cancer. AB - BACKGROUND: The role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone action or whether they are a consequence of a direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to TSH in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors. METHODS: The study population consisted of three men and seven women (Mage = 32.6 +/- 8 years) who underwent total thyroidectomy for DTC. All were receiving therapy with L-thyroxine to maintain TSH within the reference range. No patient was obese, or had hypertension, diabetes, or dyslipidemia. Patients underwent standard echo-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second recombinant human TSH (rhTSH) injection. RESULTS: Left ventricular morphology and systolic and diastolic function were normal in all patients. Levels of thyroid hormones and thyroglobulin and antithyroglobulin antibodies did not differ significantly pre- versus post-rhTSH treatment, whereas TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest (22.3 +/- 6 vs 23.2 +/- 8.7; p = 0.66) did not differ between baseline and 24 h after rhTSH, while post CPT velocity (29.3 +/- 6.8 vs 34.4 +/- 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 +/- 0.2 vs. 1.53 +/- 0.2; p < 0.01). CONCLUSIONS: rhTSH administration may improve the CFR after the non pharmacological stressor CPT in DTC patients. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium. PMID- 27558486 TI - The possible role of the insula in the epilepsy and the gambling disorder of Fyodor Dostoyevsky. AB - Background The retrospective diagnosis of Fyodor Mikhailovich Dostoyevsky's (1821 1881) neurological and psychiatric disease proves to be particularly interesting. Recent neurobiological data suggest a solution to the questions regarding the writer's retrospective diagnosis, claiming the insular cortex to be the origin of the rare ecstatic seizures. Regarding Dostoyevsky's pathological gambling, this hypothesis is consistent with another finding from recent neuroscience, namely that the malfunction of the insula could be an important underlying pathology in gambling disorder. Case study Literary and scientific overview (1928-2015) on the subjects of Dostoyevsky's epilepsy and gambling disorder. Discussion and conclusion Taking Dostoyevsky's neurological (ecstatic seizures) and psychiatric (pathological gambling) disease and the crossroads into consideration, these two disciplines make regarding the underlying pathology, we would like to suggest a speculative theory that these two disorders have a common insular pathomechanism, namely, the malfunctioning of the risk prediction-risk prediction error coding system. Furthermore, based on Dostoyevsky's case, regarding gambling disorder in general, we would like to hypothesize that the three common gambling-related cognitive distortions (near-miss effect, gambler's fallacy, and the illusion of control) can be all attributed to the impairment of the anterior insular risk prediction-risk prediction error coding system. PMID- 27558488 TI - Reshaping understandings of disability associated with age-related vision loss (ARVL): incorporating critical disability perspectives into research and practice. AB - PURPOSE: In this paper, we have sought to stimulate a critical dialog regarding the ways in which disability has been largely conceptualized and studied in literature addressing age-related vision loss (ARVL). We suggest an expansion of this largely biomedically informed research area to include alternative frameworks, namely critical disability perspectives. METHOD: To demonstrate the potential contributions of adopting a critical disability approach to enhance understandings of ARVL, this article outlined the primary tenets of the biomedical and social models of disability; the key aims, emphases, and assumptions of critical disability perspectives; and provided examples of how such an approach would lead to new research foci in the study of ARVL. RESULTS: The paper highlighted four qualities of critical disability perspectives that future ARVL research should ascribe to, including (a) a focus on interdependence over traditional notions of independence; (b) a broader conceptualization of 'normalcy'; (c) the influence of language as a means of describing or labeling disabled persons; and (d) the influence of the socio-political environment in the creation and sustainment of disability. CONCLUSIONS: This paper encouraged the incorporation of critical disability perspectives to provide new ways of conceptualizing, researching, writing about, and practicing in relation to ARVL. Implications for Rehabilitation The application of critical disability perspectives to expand the boundaries of low vision research can broaden low vision rehabilitation services (LVRS) in ways that more effectively attend to environmental features shaping and perpetuating disability for clients with age related vision loss (ARVL). Low vision research, informed by critical disability perspectives, would inform a shift away from the exclusive focus on independence towards an acknowledgment of interdependence. The integration of participatory research approaches in ARVL research could generate new insights to inform rehabilitation by enhancing space and respect for the stories and knowledge of older adults aging with vision loss. Greater attention in low vision rehabilitation should be paid to how older adults' experiences of disability are tied to both the environmental context in which they exist and by the limitations caused by their impairment. PMID- 27558487 TI - CD151 mediates netrin-1-induced angiogenesis through the Src-FAK-Paxillin pathway. AB - Crosstalk between the nervous and vascular systems is important during development and in response to injury, and the laminin-like axonal guidance protein netrin-1 has been studied for its involvement in angiogenesis and vascular remodelling. In this study, we examined the role of netrin-1 in angiogenesis and explored the underlying mechanisms. The effect of netrin-1 on brain tissues and endothelial cells was examined by immunohistochemistry and western blotting in a middle cerebral artery occlusion model and in human umbilical vein endothelial cells. Cell proliferation and cell cycle progression were assessed by the MTT assay and flow cytometry, and the Transwell and tube formation assays were used to examine endothelial cell motility and function. Netrin-1 up-regulated CD151 and VEGF concomitant with the activation of focal adhesion kinase (FAK), Src and Paxillin in vitro and in vivo and the induction of cell proliferation, migration and tube formation in vitro. Silencing of CD151 abolished the effects of netrin-1 on promoting cell migration and tube formation mediated by the activation of FAK/Src signalling. Netrin-1 promoted angiogenesis in vitro and in vivo by activating the FAK/Src/Paxillin signalling pathway through a mechanism dependent on the expression of the CD151 tetraspanin, suggesting the existence of a netrin-1/FAK/Src/CD151 signalling axis involved in the modulation of angiogenesis. PMID- 27558489 TI - Management of past MRSA-positive patients, then and NOW. PMID- 27558490 TI - Prospective risk for suicidal thoughts and behaviour in adolescents with onset, maintenance or cessation of direct self-injurious behaviour. AB - Direct self-injurious behaviour (D-SIB) is associated with suicidal behaviour and suicide risk. It is not known if D-SIB cessation reduces these risks. The aim of this study was to explore trajectories of D-SIB and their prospective influence on suicidal thoughts and behaviour during adolescence. Data (n = 506; 62.06 % females, 14.53 years) from the Saving and Empowering Young Lives in Europe study were analysed. D-SIB and suicidal thoughts and behaviour were assessed at baseline (T0), 1- (T1) and 2-year follow-up (T2). Onset and maintenance of D-SIB between T0 and T1 were associated with a two to threefold increased odds ratio for suicidal thoughts and behaviour at T2. Suicidal thoughts and behaviour in those terminating D-SIB before T1 were similar compared to those with no life time history of D-SIB. Late onset and maintenance of D-SIB prospectively indicate risk for suicidal thoughts and behaviour. This is the first study showing that D SIB cessation reduces later risk for suicidal thoughts and behaviour in adolescence. Suicide prevention efforts should set one focus on reducing adolescent D-SIB. PMID- 27558491 TI - Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine. AB - BACKGROUND: Phosphatidylcholine (PC), the major source of dietary choline, has been demonstrated to improve the capability of learning and memory in rodent and the amelioration of long-chain n-3 polyunsaturated fatty acids (PUFA) on anti aging and anti-oxidation is widely known as well. In this study, three kinds of PC were chose to demonstrate the role of different fatty acids composition on glycerol backbone in improving the brain function of mice induced by scopolamine which was used to impair cholinergic system and cause oxidative stress. METHODS: Male BALB/c mice were randomly divided into 5 groups: model (M) group, control (Con) group, egg yolk lecithin (EL) group, squid PC (SQ-PC) group and sea cucumber PC (SC-PC) group. The intraperitoneal injection of scopolamine hydrobromide (5 mg/kg) was carried out on the 8(th) of group feeding and sustained daily until the end of test. Morris water maze test was used to evaluate the improvement of cognitive decline and the activity of acetylcholinesterase (AchE), superoxide dismutase (SOD) and monoamine oxidase (MAO) and malondialdehyde (MDA) content in brain were measured to assess the physiological changes. RESULTS: In behavior test, the latency of PC groups was significantly reduced, while number of crossing the platform and time in target quadrant were increased in comparison with M group and the improvements of SQ-PC and SC-PC were better than that of EL (P < 0.05). Similar trend was observed in physiological changes. The AchE activity was effectively decreased and the SOD activity increased in hippocampus, cortex and white matter when comparing PC groups with M group. SQ-PC, SC-PC and EL respectively showed 22.82, 28.80 and 11.81 % decrease in MDA level in brain compared with M group. The MAO activity in white matter of SQ-PC, SC-PC and EL group separately depressed 33.05, 33.64 and 19.73 % in comparison with M group. No significance between SQ-PC and SC-PC was found in these indicators except the SOD activity in hippocampus and white matter. SQ-PC group had a higher SOD activity in hippocampus (103.68U/mg . prot.) and lower in white matter (120.57 U/mg . prot.) than SC-PC group (95.53 U/mg . prot. in hippocampus, 134.49 U/mg . prot. in white matter). PC rich in n-3 PUFA acted more ameliorative effects than that barely contained on the indicators above. CONCLUSIONS: Different fatty acids composition of PC all could diminish the cognitive decline and biological damage and protect the brain. EPA and DHA partly enhaced to the advantageous effects. PMID- 27558492 TI - Comparison between harvesting and preserving the spinous process for adolescent idiopathic scoliosis. AB - BACKGROUND: Spinous process has been routinely resected during posterior fusion of adolescent idiopathic scoliosis for fusion bed preparation and local autologous bone graft supplement. However, spinous process serves as an important structure in posterior ligament complex and was the anchorage of paraspinal muscle groups. With the development of pedicle screws instrumentation and the potential fusion ability in children, the need for resecting spinous process in this procedure could be further investigated. The purpose of this study was to compare the fusion rates, surgical outcomes and complications between harvesting and preserving the spinous process in posterior fusion of adolescent idiopathic scoliosis. METHODS: From January 2003 to December 2008, 104 consecutive adolescent idiopathic scoliosis patients underwent primary posterior fusion with local autologous bone grafts and following for a minimum of 24 months were reviewed. The patients were divided into a harvesting group (n = 61) with the spinous process harvested, and a preserving group (n = 43) with the spinous process preserved. Blood loss, radiographic assessments, and clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in duration of surgery and peri-operative blood transfusion between the two groups. However, blood loss was statistically greater (983 +/- 446 ml vs. 824 +/- 361 ml; p = 0.048) and duration of hospitalization was statistically longer (7.4 +/- 1.0 days vs. 6.8 +/- 0.8 days; p = 0.003) in the harvesting group. The pre- and post-operative structural curves, correction rates, sagittal profile and loss of corrections were similar in both groups. Based on radiographic evaluation, the incidences of pseudoarthrosis were similar in both groups (3/61 vs. 2/43; p = 0.95). The incidence of prescribing pain medication for back discomfort during follow-up was statistically higher in the harvesting group (16/61 vs. 4/43; p = 0.03). CONCLUSIONS: The surgical outcomes and fusion rates between harvesting and preserving the spinous process were comparable. Resecting the spinous process as local autologous bone graft may not be necessary in posterior fusion for adolescent idiopathic scoliosis patients. PMID- 27558493 TI - Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children. AB - To investigate antibiotic resistance among pathogens isolated from urines in a tertiary care children's hospital in Italy. Retrospective analysis of prospectively collected data on antibiotic susceptibility of Gram-negatives isolated from urines at the Istituto Giannina Gaslini, Genoa - Italy from 2007 to 2014. Antibiotic susceptibility was evaluated. By means of CLSI criteria from 2007 to 2010, while from 2011 EUCAST criteria were adopted. Data on susceptibility to amoxicillin-clavulanate, co-trimoxazole, cefuroxime, nitrofurantoin, fosfomycin and ciprofloxacin were evaluated for Escherichia coli, while for other Enterobacteriaceae data were collected for amoxicillin clavulanate, co-trimoxazole and ciprofloxacin and for ciprofloxacin against Pseudomonas aeruginosa. Univariate and multivariable analyses were performed for risk factors associated with resistance. A total of 4596 Gram-negative strains were observed in 3364 patients. A significant increase in the proportion of resistant strains was observed for E.coli against amoxicillin-clavulanate, cefuroxime and ciprofloxacin and for others Enterobacteriaceae against co trimoxazole and ciprofloxacin. Resistance to nitrofurantoin and fosfomycin was very infrequent in E.coli. Logistic regression analysis showed that repeated episode of urinary tract infections was a risk factor for E.coli resistance to amoxicillin-clavulanate, co-trimoxazole and cefuroxime, while admission in one of the Units usually managing children with urinary tract malformations was significantly associated to resistance to amoxicillin-clavulanate and cefuroxime. CONCLUSION: In conclusion the present study shows an increase in antibiotic resistance in pediatric bacteria isolated from urines in children, especially in presence of repeated episodes and/or urinary tract malformations. This resistance is worrisome for beta-lactams and cotrimoxazole, and start to increase also for fluoroquinolones while nitrofurantoin and fosfomycin still could represent useful drugs for oral treatment of these infections. WHAT IS KNOWN: * Infections are frequent in patients with urinary tract malformations * Antibiotic prophylaxis can select for resistant pathogens What is New: * The increase in the resistance to beta-lactams, co-trimoxazole or fluoroquinolones in pathogens causing urinary tract infections cause a reduction of drugs with oral formulations available for therapy * Old drugs like nitrofurantoin and fosfomycin can represent attractive compounds for oral treatment of urinary tract infections in children presence of resistance to other drug classes. PMID- 27558494 TI - Experimental Investigation of Electrical Conductivity and Permittivity of SC-TiO 2 -EG Nanofluids. AB - The paper presents experimental studies of dielectric properties of nanofluids based on ethylene glycol and SC-TiO2 nanoparticles with average size of 15-40 nm with various mass concentrations. The dielectric permittivity both real part and imaginary part as a function of temperature and frequency were measured. Also, dependence ac conductivity on frequency, temperature, and mass concentration were investigated. Based on the curves of ac conductivity, dc conductivity was calculated, and 400 % enhancement in dc conductivity was exposed. PMID- 27558495 TI - Enhanced Performance of Quantum Dot-Based Light-Emitting Diodes with Gold Nanoparticle-Doped Hole Injection Layer. AB - In this paper, the performance of quantum dot-based light-emitting diodes (QLEDs) comprising ZnCdSe/ZnS core-shell QDs as an emitting layer were enhanced by employing Au-doped poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate ( PEDOT: PSS) hole injection layer (HIL). By varying the concentration and dimension of Au nanoparticle (NP) dopants in PEDOT: PSS, the optimal devices were obtained with ~22-nm-sized Au NP dopant at the concentration with an optical density (OD) of 0.21. Highly bright green QLEDs with a maximum external quantum efficiency (EQE) of 8.2 % and a current efficiency of 29.1 cd/A exhibit 80 % improvement compared with devices without Au NP dopants. The improved performance may be attributed to the significant increase in the hole injection rate as a result of the introduction of Au NPs and the good matching between the resonance frequency of the localized surface plasmon resonance (LSPR) generated by the Au NPs and the emission band of QD layer, as well as the suppressed Auger recombination of QD layer due to the LSPR-induced near-field enhanced radiative recombination rate of excitons. These results are helpful for fabricating high performance QD-based applications, such as full-color displays and solid-state lighting. 80 % enhancement of efficency of quantum dot-based light-emitting diodes with gold nanoparticle doped hole-injection-layer. PMID- 27558496 TI - Uniaxial Drawing of Graphene-PVA Nanocomposites: Improvement in Mechanical Characteristics via Strain-Induced Exfoliation of Graphene. AB - Polyvinyl alcohol (PVA)-stabilized graphene nanosheets (GNS) of lateral dimension (L) ~1 MUm are obtained via liquid phase exfoliation technique to prepare its composites in the PVA matrix. These composites show low levels of reinforcements due to poor alignment of GNS within the matrix as predicted by the modified Halpin-Tsai model. Drawing these composites up to 200 % strain, a significant improvement in mechanical properties is observed. Maximum values for Young's modulus and strength are ~*4 and ~*2 higher respectively than that of neat PVA. Moreover, the rate of increase of the modulus with GNS volume fraction is up to 700 GPa, higher than the values predicted using the Halpin-Tsai theory. However, alignment along with strain-induced de-aggregation of GNS within composites accounts well for the obtained results as confirmed by X-ray diffraction (XRD) characterization. PMID- 27558499 TI - Anxiety in teenage girls rises sharply in past decade, finds study. PMID- 27558497 TI - Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis. AB - BACKGROUND: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). RESULTS: The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade >= 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). CONCLUSION: The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab. PMID- 27558498 TI - Roles of different IRES-dependent FGF2 isoforms in the acquisition of the major aggressive features of human metastatic melanoma. AB - : Fibroblast growth factor 2 (FGF2) is involved in many physiological and pathological processes. Fgf2 deregulation contributes to the acquisition of malignant features of melanoma and other cancers. FGF2 is an alternative translation product expressed as five isoforms, a low-molecular-weight (18 KDa) and four high-molecular-weight (22, 22.5, 24, 34 KDa) isoforms, with different subcellular distributions. An internal ribosomal entry site (IRES) in its mRNA controls the translation of all the isoforms with the exception for the cap dependent 34 KDa. The 18-KDa isoform has been extensively studied, while very few is known about the roles of high molecular weight isoforms. FGF2 is known to promote melanoma development and progression. To disclose the differential contribution of FGF2 isoforms in melanoma, we forced the expression of IRES dependent low-molecular-weight (LMW, 18 KDa) and high-molecular-weight (HMW, 22, 22.5, 24 KDa) isoforms in a human metastatic melanoma cell line. This comparative study highlights that, while LMW isoform confers stem-like features to melanoma cells and promotes angiogenesis, HMW isoforms induce higher migratory ability and contribute to tumor perfusion by promoting vasculogenic mimicry (VM) when endothelial cell-driven angiogenesis is lacking. To conclude, FGF2 isoforms mainly behave in specific, antithetical manners, but can cooperate in different steps of tumor progression, providing melanoma cells with major malignant features. KEY MESSAGE: FGF2 is an alternative translation product expressed as different isoforms termed LMW and HMW. FGF2 is involved in melanoma development and progression. HMW FGF2 isoforms enhance in vitro motility of melanoma cells. LMW FGF2 confers stem-like features and increases in vivo metastasization. LMW FGF2 promotes angiogenesis while HMW FGF2 induces vasculogenic mimicry. PMID- 27558500 TI - Follow-up over 20 months confirms gains of online behavioural training in frequent episodic migraine. AB - Aim This study examined the change over 20 months in 178 participants with frequent episodic migraine under adequate treatment as usual, who had completed online behavioural training (oBT) in migraine self-management either directly (group 1, n = 120) or after 10 months of watchful waiting (group 2, n = 58). Methods Participants completed questionnaires and an online headache diary and migraine monitor following the International Classification of Headache Disorders at T0 (baseline), T1 (post-training), T2 (6-month follow-up; extended baseline in group 2), T3 (post-training, group 2 only) and T4 (group 1: 16-month follow-up; group 2: 6-month follow-up). Statistical analyses were conducted on the observed data without imputation of missing observations. Results Both groups were highly comparable. The data over time revealed benefits in response to oBT, with significant between-group differences in the change achieved in the training episodes T2-T0 (group 1) and T4-T2 (group 2). Improved attack frequency ( M = 23%) was higher in participants with more (i.e. 4-6) attacks per month at baseline, and the effects of oBT were durable over 16 months of follow-up. Conclusions oBT is beneficial in frequent episodic migraine, which deserves special efforts in care. Self-management variants such as oBT reach patients easily and supplement these efforts with durable results. PMID- 27558501 TI - Characteristics of headache during and after digital substraction angiography: A critical re-appraisal of the ICHD-3 criteria. AB - Introduction Headache is a frequent but neglected side effect of angiography, and the criteria for angiography related headache have been based on only a few studies. Methods One-hundred and thirty nine patients who underwent cerebral angiography and 30 controls who underwent peripheral angiography participated in this prospective, non-randomized, case-control study. Participants were instructed to tell the angiography staff in case a headache developed and were questioned about their headache just after, 24 hours after, and one week after angiography. Results In the cerebral angiography group 42 patients (30.2%) had procedural headache compared to three of the controls (10%). Two different types of headache related to angiography were observed: one during angiography, which was related to contrast injection, and the other occuring within 24 hours. Both headaches were more frequent in patients with a history of primary headache, but were distinctly different from the premorbid headache. Headache characteristics are described in detail. Discussion Both types of headache related to angiography did not match the ICHD-3beta criteria for angiography headache, but were similar to headaches reported in studies that were not included in the current criteria. The timing and characteristics of these headaches are discussed in the light of our and previous reports. We suggest that the present ICHD-3 beta criteria are inadequate in properly defining angiography headache and should be revised in the light of the present literature. PMID- 27558502 TI - Treatment of raw and ozonated oil sands process-affected water under decoupled denitrifying anoxic and nitrifying aerobic conditions: a comparative study. AB - Batch experiments were performed to evaluate biodegradation of raw and ozonated oil sands process-affected water (OSPW) under denitrifying anoxic and nitrifying aerobic conditions for 33 days. The results showed both the anoxic and aerobic conditions are effective in degrading OSPW classical and oxidized naphthenic acids (NAs) with the aerobic conditions demonstrating higher removal efficiency. The reactors under nitrifying aerobic condition reduced the total classical NAs of raw OSPW by 69.1 %, with better efficiency for species of higher hydrophobicity. Compared with conventional aerobic reactor, nitrifying aerobic condition substantially shortened the NA degradation half-life to 16 days. The mild-dose ozonation remarkably accelerated the subsequent aerobic biodegradation of classical NAs within the first 14 days, especially for those with long carbon chains. Moreover, the ozone pretreatment enhanced the biological removal of OSPW classical NAs by leaving a considerably lower final residual concentration of 10.4 mg/L under anoxic conditions, and 5.7 mg/L under aerobic conditions. The combination of ozonation and nitrifying aerobic biodegradation removed total classical NAs by 76.5 % and total oxy-NAs (O3-O6) by 23.6 %. 454 Pyrosequencing revealed that microbial species capable of degrading recalcitrant hydrocarbons were dominant in all reactors. The most abundant genus in the raw and ozonated anoxic reactors was Thauera (~56 % in the raw OSPW anoxic reactor, and ~65 % in the ozonated OSPW anoxic reactor); whereas Rhodanobacter (~40 %) and Pseudomonas (~40 %) dominated the raw and ozonated aerobic reactors, respectively. Therefore, the combination of mild-dose ozone pretreatment and subsequent biological process could be a competent choice for OSPW treatment. PMID- 27558503 TI - Molecular graph convolutions: moving beyond fingerprints. AB - Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph-atoms, bonds, distances, etc.-which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. PMID- 27558504 TI - Skin fungal community and its correlation with bacterial community of urban Chinese individuals. AB - BACKGROUND: High-throughput sequencing has led to increased insights into the human skin microbiome. Currently, the majority of skin microbiome investigations are limited to characterizing prokaryotic communities, and our understanding of the skin fungal community (mycobiome) is limited, more so for cohorts outside of the western hemisphere. Here, the skin mycobiome across healthy Chinese individuals in Hong Kong are characterized. RESULTS: Based on a curated fungal reference database designed for skin mycobiome analyses, previously documented common skin colonizers are also abundant and prevalent in this cohort. However, genera associated with local terrains, food, and medicine are also detected. Fungal community composition shows interpersonal (Bray-Curtis ANOSIM = 0.398) and household (Bray-Curtis ANOSIM = 0.134) clustering. Roles of gender and age on diversity analyses are test- and site-specific, and, contrary to bacteria, the effect of household on fungal community composition dissimilarity between samples is insignificant. Site-specific, cross-domain positive and negative correlations at both community and operational taxonomic unit levels may uncover potential relationships between fungi and bacteria on skin. CONCLUSIONS: The studied Chinese population presents similar major fungal skin colonizers that are also common in western populations, but local outdoor environments and lifestyles may also contribute to mycobiomes of specific cohorts. Cohabitation plays an insignificant role in shaping mycobiome differences between individuals in this cohort. Increased understanding of fungal communities of non-western cohorts will contribute to understanding the size of the global skin pan-mycobiome, which will ultimately help understand relationships between environmental exposures, microbial populations, and the health of global humans. PMID- 27558506 TI - Barriers to HPV immunization among blacks and latinos: a qualitative analysis of caregivers, adolescents, and providers. AB - BACKGROUND: Despite recommendations that 11-12-year-olds receive the full three shot Human papillomavirus (HPV) vaccine series, national HPV immunization coverage rates remain low. Disparities exist, with Blacks and Latinos being less likely than Whites to complete the series. We aimed to identify and compare barriers to HPV immunization perceived by healthcare providers, Black and Latino adolescents, and their caregivers to inform a clinic-based intervention to improve immunization rates. METHODS: We conducted semi-structured interviews between March and July 2014 with Black and Latino adolescents (n = 24), their caregivers (n = 24), and nurses (n = 18), and 2 focus groups with 18 physicians recruited from two pediatric primary care clinics. Qualitative protocol topics included: general perceptions and attitudes towards vaccines; HPV knowledge; and perceived individual and systems-level barriers affecting vaccine initiation and completion. RESULTS: Themes were identified and organized by individual and systems-level barriers to HPV immunization. Adolescents and their caregivers, particularly Blacks, expressed concerns about HPV being an untested, "newer" vaccine. All families felt they needed more information on HPV and found it difficult to return for multiple visits to complete the vaccine series. Providers focused on challenges related to administering multiple vaccines simultaneously, and perceptions of parental reluctance to discuss sexually transmitted infections. CONCLUSIONS: Optimizing HPV immunization rates may benefit from a multi-pronged approach to holistically address provider, structural, and individual barriers to care. Further research should examine strategies for providing multiple modalities of support for providers, including a routinized system of vaccine promotion and delivery, and for addressing families' concerns about vaccine safety and efficacy. PMID- 27558508 TI - An approach to improve the care of mid-life women through the implementation of a Women's Health Assessment Tool/Clinical Decision Support toolkit. AB - The objectives of this study are to describe the implementation process of the Women's Health Assessment Tool/Clinical Decision Support toolkit and summarize patients' and clinicians' perceptions of the toolkit. The Women's Health Assessment Tool/Clinical Decision Support toolkit was piloted at three clinical sites over a 4-month period in Washington State to evaluate health outcomes among mid-life women. The implementation involved a multistep process and engagement of multiple stakeholders over 18 months. Two-thirds of patients (n = 76/110) and clinicians (n = 8/12) participating in pilot completed feedback surveys; five clinicians participated in qualitative interviews. Most patients felt more prepared for their annual visit (69.7%) and that quality of care improved (68.4%) while clinicians reported streamlined patient visits and improved communication with patients. The Women's Health Assessment Tool/Clinical Decision Support toolkit offers a unique approach to introduce and address some of the key health issues that affect mid-life women. PMID- 27558507 TI - Reduced induction of anti-PF4/heparin antibody in RA patients after total knee arthroplasty. AB - BACKGROUND: Heparin-induced thrombocytopenia is caused by antibodies (Abs) specific to platelet factor 4 (PF4)/heparin complexes. In this study, we evaluated the rates of seroconversion of anti-PF4/heparin Ab between patients with rheumatoid arthritis (RA) and with osteoarthritis (OA) who underwent total knee arthroplasty. METHODS: The subjects of this randomized controlled trial were 124 patients who underwent total knee arthroplasty (TKA) and received edoxaban with or without a foot pump as thromboprophylaxis. We measured anti-PF4/heparin Abs before and 10 days after surgery, as well as preoperative PF4, using commercially available ELISAs. We also used the database of J-PSVT, a hospital based, prospective cohort study designed to document the effectiveness of thromboprophylactic agents during arthroplasty. RESULTS: The rates of seroconversion to anti-PF4/heparin Ab were lower in RA patients (4.0 %) than in OA patients (25.5 %). The anti-PF4/heparin IgG optical density (OD) values did not differ before and after surgery in RA patients. In contrast, there was a significant increase in anti-PF4/heparin IgG OD values in OA patients after TKA. In the J-PSVT data, the postoperative seroconversion rates of anti-PF4/heparin Ab were lower in RA patients (10.4 %) than in OA patients (21.8 %) who received fondaparinux. The titers of anti-CCP Ab were significantly lower in RA patients with postoperative ant-PF4/heparin Ab compared with those without postoperative ant-PF4/heparin Ab There was no significant difference in preoperative PF4 levels between RA patients and OA patients. The heparin-binding affinity of the circulating PF4 was similar between RA patients and OA patients; however, the IgG fractions isolated from the sera of RA patients contained PF4 more frequently (69.2 %) than those from OA patients (10.2 %). CONCLUSIONS: Our results showed a reduced likelihood of postoperative anti-PF/heparin Ab production in RA patients compared with OA patients. This suggests that the mechanisms underlying the anti PF4 immune response in RA patients differ from the mechanisms of the anti PF4/heparin immune response seen in OA patients after joint replacement. TRIAL REGISTRATION: ISRCTN 18090286. Registered 8 July 2016. PMID- 27558509 TI - Safe prescribing training provision for junior doctors: is this optimal? AB - BACKGROUND: The aim of this study was to determine the training provisions in practical safe prescribing for foundation doctors in NHS hospitals located in the South Thames region. METHODS: A web-based questionnaire was distributed by e-mail to all 1762 foundation doctors in the South Thames Foundation School (STFS) region. In addition, a separate questionnaire was distributed to prescribing training Leads at 15 NHS Hospital Trusts. Quantitative data were analysed using descriptive statistics and thematic analysis was performed on qualitative data. RESULTS: Trainers: 10 Prescribing Leads (67 %) responded. Of the 9 NHS Trusts that offered safe prescribing training in their induction programme, 5 included a practical prescribing session. By the end of the foundation year, 6 NHS Trusts had provided at least one dedicated practical prescribing session for F1s compared with 2 NHS Trusts for F2s. Trainees: A total of 124 foundation trainees (7.2 %) responded (69 F1s and 55 F2s). 87 % of F1s received dedicated training in safe prescribing at their Trust induction (n = 60) in comparison to 49 % of F2s (n = 27). 80 % of F1s (n = 55) had a practical prescribing session during induction versus 27 % of F2s (n = 15). The difference was significant, X (2) (1, N = 124) = 34.23, p <0.0001. Emerging themes from qualitative data included, recognition of medical education as a continuum, importance of working relationships with pharmacists and neglect of F2s. CONCLUSIONS: There appears to be a lack of emphasis on the training of F2 doctors in practical safe prescribing compared with F1 doctors. There should be standardisation of safe prescribing training provisions, particularly in the induction period and for F2 doctors. PMID- 27558510 TI - How time delay and network design shape response patterns in biochemical negative feedback systems. AB - BACKGROUND: Negative feedback in combination with time delay can bring about both sustained oscillations and adaptive behaviour in cellular networks. Here, we study which design features of systems with delayed negative feedback shape characteristic response patterns with special emphasis on the role of time delay. To this end, we analyse generic two-dimensional delay differential equations describing the dynamics of biochemical signal-response networks. RESULTS: We investigate the influence of several design features on the stability of the model equilibrium, i.e., presence of auto-inhibition and/or mass conservation and the kind and/or strength of the delayed negative feedback. We show that auto inhibition and mass conservation have a stabilizing effect, whereas increasing abruptness and decreasing feedback threshold have a de-stabilizing effect on the model equilibrium. Moreover, applying our theoretical analysis to the mammalian p53 system we show that an auto-inhibitory feedback can decouple period and amplitude of an oscillatory response, whereas the delayed feedback can not. CONCLUSIONS: Our theoretical framework provides insight into how time delay and design features of biochemical networks act together to elicit specific characteristic response patterns. Such insight is useful for constructing synthetic networks and controlling their behaviour in response to external stimulation. PMID- 27558511 TI - Nonlinear deformation and localized failure of bacterial streamers in creeping flows. AB - We investigate the failure of bacterial floc mediated streamers in a microfluidic device in a creeping flow regime using both experimental observations and analytical modeling. The quantification of streamer deformation and failure behavior is possible due to the use of 200 nm fluorescent polystyrene beads which firmly embed in the extracellular polymeric substance (EPS) and act as tracers. The streamers, which form soon after the commencement of flow begin to deviate from an apparently quiescent fully formed state in spite of steady background flow and limited mass accretion indicating significant mechanical nonlinearity. This nonlinear behavior shows distinct phases of deformation with mutually different characteristic times and comes to an end with a distinct localized failure of the streamer far from the walls. We investigate this deformation and failure behavior for two separate bacterial strains and develop a simplified but nonlinear analytical model describing the experimentally observed instability phenomena assuming a necking route to instability. Our model leads to a power law relation between the critical strain at failure and the fluid velocity scale exhibiting excellent qualitative and quantitative agreeing with the experimental rupture behavior. PMID- 27558512 TI - Physicochemical properties of iron oxide nanoparticles that contribute to cellular ROS-dependent signaling and acellular production of hydroxyl radical. AB - While nanoparticles (NPs) are increasingly used in a variety of consumer products and medical applications, some of these materials have potential health concerns. Macrophages are the primary responders to particles that initiate oxidative stress and inflammatory reactions. Here, we utilized six flame-synthesized, engineered iron oxide NPs with various physicochemical properties (e.g. Fe oxidation state and crystal size) to study their interactions with RAW 264.7 macrophages, their iron solubilities, and their abilities to produce hydroxyl radical in an acellular assay. Both iron solubility and hydroxyl radical production varied between NPs depending on crystalline diameter and surface area of the particles, but not on iron oxidation state. Macrophage treatment with the iron oxide NPs showed a dose-dependent increase of heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO-1). The nuclear factor (NF)-erythroid-derived 2 (E2)-related factor 2 (Nrf2) modulates the transcriptional activity of antioxidant response element (ARE)-driven genes, such as HO-1 and NQO-1. Here, we show that the iron oxide NPs activate Nrf2, leading to its increased nuclear accumulation and enhanced Nrf2 DNA-binding activity in NP-treated RAW 264.7 macrophages. Iron solubility and acellular hydroxyl radical generation depend on the physical properties of the NPs, especially crystalline diameter; however, these properties are weakly linked to the activation of cellular signaling of Nrf2 and the expression of oxidative stress markers. Overall, our work shows for the first time that iron oxide nanoparticles induce cellular marker genes of oxidative stress and that this effect is transcriptionally mediated through the Nrf2-ARE signaling pathway in macrophages. PMID- 27558514 TI - Differentially regulated high-affinity iron assimilation systems support growth of the various cell types in the dimorphic pathogen Talaromyces marneffei. AB - Iron is a key trace element important for many biochemical processes and its availability varies with the environment. For human pathogenic fungi iron acquisition can be particularly problematical because host cells sequester free iron as part of the acute-phase response to infection. Fungi rely on high affinity iron uptake systems, such as reductive iron assimilation (RIA) and siderophore-mediated iron uptake (non-RIA). These have been extensively studied in pathogenic fungi that exist outside of host cells, but much less is known for intracellular fungal pathogens. Talaromyces marneffei is a dimorphic fungal pathogen endemic to Southeast Asia. In the host T. marneffei resides within macrophages where it grows as a fission yeast. T. marneffei has genes of both iron assimilation systems as well as a paralogue of the siderophore biosynthetic gene sidA, designated sidX. Unlike other fungi, deletion of sidA or sidX resulted in cell type-specific effects. Mutant analysis showed that T. marneffei yeast cells also employ RIA for iron acquisition, providing an additional system in this cell type that differs substantially from hyphal cells. These data illustrate the specialized iron acquisition systems used by the different cell types of a dimorphic fungal pathogen and highlight the complexity in siderophore biosynthetic pathways amongst fungi. PMID- 27558513 TI - A One Health overview, facilitating advances in comparative medicine and translational research. AB - TABLE OF CONTENTS: A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman. PMID- 27558515 TI - Does Formaldehyde Increase Cell Free DNA in Maternal Plasma Specimens? AB - BACKGROUND: There have been conflicting observations reported in the literature regarding the effects of formaldehyde in the recovery of cell free fetal DNA (CFF DNA) from maternal plasma. The aim of the present study was to assess the effect of formaldehyde treatment on circulating cell free DNA. METHODS: We conducted this study using blood specimens collected from 11 pregnant women, each of whom was carrying a male fetus. DYS14 and HBB real time assays were performed to quantify fetal and total circulating cell free DNA from formaldehyde treated and untreated maternal plasma specimens, respectively. RESULTS: The concentration of total circulating cell free DNA in formaldehyde-treated maternal plasma was reduced, compared with untreated maternal plasma (n = 11; P = .02). The percentage of CFF DNA between formaldehyde-treated and untreated maternal plasma specimens did not differ significantly (n = 11; P = .15). CONCLUSION: Addition of formaldehyde does not significantly enhance the proportion of cell free fetal DNA when blood specimens are processed without delay. PMID- 27558516 TI - Miniature Surface Plasmon Polariton Amplitude Modulator by Beat Frequency and Polarization Control. AB - The miniaturization of modulators keeps pace for the compact devices in optical applications. Here, we present a miniature surface plasmon polariton amplitude modulator (SPPAM) by directing and interfering surface plasmon polaritons on a nanofabricated chip. Our results show that this SPPAM enables two kinds of modulations. The first kind of modulation is controlled by encoding angular frequency difference from a Zeeman laser, with a beat frequency of 1.66 MHz; the second of modulation is validated by periodically varying the polarization states from a polarization generator, with rotation frequencies of 0.5-10 k Hz. In addition, the normalized extinction ratio of our plasmonic structure reaches 100. Such miniaturized beat-frequency and polarization-controlled amplitude modulators open an avenue for the exploration of ultrasensitive nanosensors, nanocircuits, and other integrated nanophotonic devices. PMID- 27558517 TI - Biological treatment of saline-alkali soil by Sulfur-oxidizing bacteria. AB - The western area of the Jilin province, a typical seasonal frost region, is located in the southern Songnen plain of China. Significantly salinized soils are widely distributed on the Songnen plain in western Jilin. Soil salinization can cause degradation of cultivated land and grass, which threatens the human environment. To investigate the treatment of saline-alkali soil, a laboratory test was conducted to evaluate the ability of sulfur-oxidizing bacteria to improve the performance of saline-alkali soil in western Jilin. The results showed that sulfur-oxidizing bacteria treatment was suitable for the soil from pH 7.5 to 8, and 50 ml thiobacillusthiooxidans showed the best improvement to the saline-alkali soil. PMID- 27558518 TI - Discordant reporting of nonmedical opioid use. PMID- 27558519 TI - Discrimination of botanical origins for Chinese honey according to free amino acids content by high-performance liquid chromatography with fluorescence detection with chemometric approaches. AB - BACKGROUND: The contents of 18 free amino acids in 87 Chinese honey samples from four botanical origins (linden, acacia, vitex and rape) were determined by developing a high-performance liquid chromatography with fluorescence detector (HPLC-FLD) method with an in-loop automated pre-column derivatization. The free amino acid profiles of these samples were used to construct a statistical model to distinguish honeys from various floral origins. RESULTS: The average contents of all free amino acids in linden honey were lower than in the other three types of honey. Phenylalanine was particularly useful in the present study because its average content in vitex honey was far higher than in any other honey samples. There is no doubt that both phenylalanine and tyrosine can be considered as the marker free amino acid in Chinese vitex honey. Principal component analysis (PCA) was conducted based on 15 free amino acids and showed significant differences among the honey samples. The cumulative variance for the first two components was 80.62%, and the four principal components can explain 94.18% of the total variance. In the two first component scores, the honey samples can be separated according to their botanical origins. Cluster analysis of amino acid data also revealed that the botanical origins of honey samples correlated with their amino acid content. Back-propagation artificial neural network (BP-ANN) and naive Bayes methods were employed to construct the classification models. The results revealed an excellent separation among honey samples according to their botanical origin with 100% accuracy in model training for both BP-ANN and naive Bayes. CONCLUSION: It indicated that the free amino acid profile determined by HPLC-FLD can provide sufficient information to discriminate honey samples according to their botanical origins. (c) 2016 Society of Chemical Industry. PMID- 27558520 TI - Shaping polymersomes into predictable morphologies via out-of-equilibrium self assembly. AB - Polymersomes are bilayer vesicles, self-assembled from amphiphilic block copolymers. They are versatile nanocapsules with adjustable properties, such as flexibility, permeability, size and functionality. However, so far no methodological approach to control their shape exists. Here we demonstrate a mechanistically fully understood procedure to precisely control polymersome shape via an out-of-equilibrium process. Carefully selecting osmotic pressure and permeability initiates controlled deflation, resulting in transient capsule shapes, followed by reinflation of the polymersomes. The shape transformation towards stomatocytes, bowl-shaped vesicles, was probed with magnetic birefringence, permitting us to stop the process at any intermediate shape in the phase diagram. Quantitative electron microscopy analysis of the different morphologies reveals that this shape transformation proceeds via a long-predicted hysteretic deflation-inflation trajectory, which can be understood in terms of bending energy. Because of the high degree of controllability and predictability, this study provides the design rules for accessing polymersomes with all possible different shapes. PMID- 27558521 TI - Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma: Validation in a Chinese cohort. AB - AIM: The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study. METHODS: The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared. RESULTS: The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1 year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and chi2 value of likelihood ratio test. CONCLUSIONS: The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted. PMID- 27558522 TI - Preparation and evaluation of niosome gel containing acyclovir for enhanced dermal deposition. AB - Niosomes suggest a versatile vesicle delivery system with possible transport of drugs via topical route for skin delivery. The aim of the present research was to optimize niosome gel formulation of acyclovir and to evaluate in both in vitro and in vivo rabbit model. Niosome formulations were formulated by coacervation phase separation technique with different ratios of nonionic surfactants, phospholipids and cholesterol using 32 factorial design. Altering the surfactant concentration has influenced the drug entrapment, but not vesicle size. At high surfactant combinations, the acyclovir release from niosomes was strongly influenced by cholesterol:lecithin ratio. Ex vivo drug permeation data indicate substantial difference in flux values and was influenced by the niosome composition. Ex vivo studies using formulation (B8) for drug deposition indicate greater amount of niosome being diffused into the skin layers and formed a depot, compared to commercial acyclovir cream (control). Two distinct dermatopharmacokinetic profiles were observed, in vivo, for niosome gel formulation (B8) and control, which were analog to the profiles observed with ex vivo deposition studies. In vivo plasma drug level suggests low systemic exposure of acyclovir (Cmax: 9.44 +/- 2.27 ng/mL and 14.54 +/- 3.11 ng/mL for niosome formulation and control, respectively). Comparison of kinetic data of acyclovir in the stratum corneum and plasma signifies that the niosome formulation forms a depot in the epidermis or dermis region. This study concludes that the niosome gel formulation (B8) could be a viable vesicular system for an impressive transdermal delivery of acyclovir by topical application. PMID- 27558523 TI - Long-term time-lapse microscopy of C. elegans post-embryonic development. AB - We present a microscopy technique that enables long-term time-lapse microscopy at single-cell resolution in moving and feeding Caenorhabditis elegans larvae. Time lapse microscopy of C. elegans post-embryonic development is challenging, as larvae are highly motile. Moreover, immobilization generally leads to rapid developmental arrest. Instead, we confine larval movement to microchambers that contain bacteria as food, and use fast image acquisition and image analysis to follow the dynamics of cells inside individual larvae, as they move within each microchamber. This allows us to perform fluorescence microscopy of 10-20 animals in parallel with 20 min time resolution. We demonstrate the power of our approach by analysing the dynamics of cell division, cell migration and gene expression over the full ~48 h of development from larva to adult. Our approach now makes it possible to study the behaviour of individual cells inside the body of a feeding and growing animal. PMID- 27558524 TI - Effective connectivity in temporal lobe epilepsy with hippocampal sclerosis. AB - OBJECTIVE: We hypothesized that temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS) showed differences in their limbic networks. This study aimed to evaluate the role of the thalamus in TLE patients with HS. MATERIALS AND METHODS: Twenty-nine TLE patients with HS and 30 controls were enrolled in this study. In addition, we included eight TLE patients without HS as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the limbic structures, including the hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. Moreover, we quantified correlations between epilepsy duration and the volumes of these structures. RESULTS: There was a statistically significant effective connectivity from the hippocampus to the thalamus in TLE patients with HS. Moreover, the volumes of the left and right thalamus were negatively correlated with epilepsy duration (r=-.42, P=.0315 and r=-.52, P=.0062, respectively). However, neither TLE patients without HS nor normal controls had a significant effective connectivity from the hippocampus to the thalamus. CONCLUSIONS: The limbic networks of TLE patients with and without HS could be different, and the thalamus might play a critical role in TLE patients with HS. PMID- 27558525 TI - Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach. AB - PURPOSE: Right ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS. METHODS: We retrospectively measured changes in the following RV parameters from a pre-ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift. RESULTS: Over 24 months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4 mm pre-ARDS to 16.3 mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67 m/s pre-ARDS to 3.31 m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre-ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO2 /FiO2 ratios), P=.004, and was lower among 30-day nonsurvivors compared with survivors, P=.002. CONCLUSIONS: Mild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality. PMID- 27558526 TI - Optimization of organic acid pretreatment of wheat straw. AB - The objective of this study was to determine the effectiveness of different organic acids (maleic, succinic, and oxalic acid) on enzymatic hydrolysis and fermentation yields of wheat straw. It was also aimed to optimize the process conditions (temperature, acid concentration, and pretreatment time) by using response surface methodology (RSM). In line with this objective, the wheat straw samples were pretreated at three different temperatures (170, 190, and 210 degrees C), acid concentrations (1%, 3%, and 5%) and pretreatment time (10, 20, and 30 min). The findings show that at extreme pretreatment conditions, xylose was solubilized in liquid phase, causing an increase in cellulose and lignin content of biomass. Enzymatic hydrolysis experiments revealed that maleic and oxalic acids were quite effective at achieving high sugar yields (>90%) from wheat straw. In contrast, the highest sugar yields were 50-60%, when the samples were pretreated with succinic acid, indicating that succinic acid was not as effective. The optimum process conditions for maleic acid were, 210 degrees C, 1.08% acid concentration, and 19.8 min; for succinic acid 210 degrees C, 5% acid concentration, and 30 min; for oxalic acid 210 degrees C, 3.6% acid concentration, and 16.3 min. The ethanol yields obtained at optimum conditions were 80, 79, and 59% for maleic, oxalic and succinic acid, respectively. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1487-1493, 2016. PMID- 27558527 TI - Household-level correlates of children's physical activity levels in and across 12 countries. AB - OBJECTIVE: Household factors (electronic media equipment, play equipment, physical activity in the home, and social support) have been associated with childhood moderate- to vigorous-intensity physical activity (MVPA), but little is known about how these factors differ across diverse countries. The objective was to explore household correlates of objective MVPA in children from 12 countries. METHODS: Overall, 5,859 nine- to eleven-year-old children from 12 countries representing a range of human and socioeconomic development indicators wore an accelerometer for 7 days and parents reported on household factors. Multilevel general linear models explored associations among household factors and MVPA variables controlling for age, sex, and parental education. RESULTS: Across sites, children with at least one piece of bedroom electronic media had lower MVPA (~4 min/day; P < 0.001) than those who did not. More frequent physical activity in the home and yard, ownership of more frequently used play equipment, and higher social support for physical activity were associated with more MVPA (all P < 0.001). The association between play equipment ownership and MVPA was inconsistent across countries (interaction P < 0.01). CONCLUSIONS: With the exception of play equipment ownership, modifiable household factors showed largely consistent and important associations with MVPA across high-, mid-, and low-income countries. PMID- 27558528 TI - Enantioselective Synthesis of (+)-Peganumine A. AB - A gram-scale enantioselective total synthesis of (+)-peganumine A was accomplished in 7 steps from commercially available 6-methoxytryptamine. Key steps included (a) a Liebeskind-Srogl cross-coupling; (b) a one-pot construction of the tetracyclic skeleton from an omega-isocyano-gamma-oxo-aldehyde via a sequence of an unprecedented C-C bond forming lactamization and a transannular condensation; (c) a one-pot organocatalytic process merging two achiral building blocks into an octacyclic structure via a sequence of enantioselective Pictet Spengler reaction followed by a transannular cyclization. This last reaction created two spirocycles and a 2,7-diazabicyclo[2.2.1]heptan-3-one unit with excellent control of both the absolute and relative stereochemistry of the two newly created quaternary stereocenters. PMID- 27558529 TI - Prognostic Significance of the Preoperative Lymphocyte to Monocyte Ratio in Patients With Stage I Non-Small Cell Lung Cancer Undergoing Complete Resection. AB - In this study, we investigated the correlation between lymphocyte to monocyte ratio (LMR) and clinical outcomes in stage I non-small cell lung cancer (NSCLC) patients. A total of 439 stage I NSCLC patients were enrolled in this study. Multivariate analyses identified LMR as an independent prognostic factor for recurrence-free survival and overall survival (hazard ratio (HR: 0.469, 95% Confidence Interval (CI): 0.325-0.677, and p < 0.001, and HR: 0.478, 95% CI: 0.332-0.688, and p < 0.001; respectively). Compared with the high LMR group, the proportion of patients who developed distant metastasis was significantly higher in the low LMR group. PMID- 27558530 TI - Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study. AB - The clinical presentation of diabetes sometimes overlaps, contributing to ambiguity in the diagnosis. Thus, circulating pancreatic islet-enriched microRNAs (miRNAs) might be useful biomarkers of beta-cell injury/dysfunction that would allow more accurate subtyping of diabetes. We measured plasma levels of selected miRNAs in subjects with prediabetes (n = 12), type 2 diabetes (T2D, n = 31), latent autoimmune diabetes of adults (LADA, n = 6) and type 1 diabetes (T1D, n = 16) and compared them to levels in healthy control subjects (n = 27). The study was conducted at the Translational Research Institute for Metabolism and Diabetes (TRI-MD), Florida Hospital. MiRNAs including miR-375 (linked to beta-cell injury), miR-21 (associated with islet inflammation), miR-24.1, miR-30d, miR-34a, miR-126, miR-146, and miR-148a were significantly elevated in subjects with various forms of diabetes compared to healthy controls. Levels of several miRNAs were significantly correlated with glucose responses during oral glucose tolerance testing, HbA1c, beta-cell function, and insulin resistance in healthy controls, prediabetes, and T2D. These data suggest that miRNAs linked to beta cell injury and islet inflammation might be useful biomarkers to distinguish between subtypes of diabetes. This information could be used to predict progression of the disease, guide selection of optimal therapy and monitor responses to interventions, thus improving outcomes in patients with diabetes. PMID- 27558531 TI - Down-regulation of SerpinB2 is associated with gefitinib resistance in non-small cell lung cancer and enhances invadopodia-like structure protrusions. AB - The failure of targeted therapy due to the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is considered a major problem in the treatment of non-small cell lung cancer (NSCLC) patients. SerpinB2, a component of the urokinase plasminogen activator (uPA) system, has been recognized as a biomarker for the progression and metastasis of lung cancer. Nevertheless, the relationship between SerpinB2 and EGFR-TKI resistance has not been elucidated. Here, we report that SerpinB2 is down-regulated in gefitinib resistant (H292-Gef) cells compared to gefitinib-sensitive (H292) cells. The low SerpinB2 levels in H292-Gef cells were also associated with an enhancement in invasiveness and increase in the length of invadopodia-like structures in the cells. The effect on invasiveness and gefitinib sensitivity was confirmed by knockdown and overexpression of SerpinB2. In addition, the possibility to overcome the resistance through the up-regulation of SerpinB2 was supported by employing an antitumor agent yuanhuadine (YD). Treatment with YD effectively elevated SerpinB2 levels and suppressed invasive properties in H292-Gef cells. Collectively, these findings demonstrate the prospective role of SerpinB2 as a novel biomarker for acquired gefitinib resistance and a potential target for NSCLC treatment. PMID- 27558532 TI - Formation of Ni-Co-MoS2 Nanoboxes with Enhanced Electrocatalytic Activity for Hydrogen Evolution. AB - Nickel and cobalt incorporated MoS2 nanoboxes are synthesized via the reaction between Ni-Co Prussian blue analogue nanocubes and ammonium thiomolybdate. Due to the structural and compositional advantages, these well-defined nanoboxes manifest enhanced electrochemical activity as an electrocatalyst for hydrogen evolution reaction. PMID- 27558533 TI - Developing an objective method for analyzing vital signs changes in neonates during general anesthesia. AB - BACKGROUND: Commonly used general anesthetics are considered to be neurotoxic to the developing rodent brain, leading to poor long-term outcome. However, it is unclear whether these rodent studies can be extrapolated to the human neonate. Given that anesthesia for urgent neonatal surgery cannot be avoided, it is vitally important to assess other factors that may impact neurological outcome following anesthesia and surgery. OBJECTIVE: The purpose of this study is to identify thresholds for detecting vital sign deviations, which may have the potential for affecting neurological outcome following anesthesia and surgery in neonates. These data may be suitable to identify targets for prospective quality improvement projects and guide future research for strategies to reduce detrimental neurocognitive outcomes. METHODS: A retrospective analysis of vital sign data was performed for neonates (age <=28 days), undergoing noncardiac surgery over a 4-year period (2010-2013). Thresholds for detecting bradycardia, tachycardia, hypothermia, hyperthermia, hypertension, hypotension, hypocarbia, hypoxemia, significant changes in mean arterial blood pressure, and periods of high inspired oxygen concentration, were proposed. Selected chart review, to identify additional risk factors, and identify sources of data artifact, was performed for 224 cases. RESULTS: Data from 435 procedures in neonates, with median (IQR [range]) ages of 6 (2-16 [0-28]) days were available for analysis. Five (3-6 [0-12]) rule deviations per case were observed; only 11 cases had no rule deviations. Hypothermia was observed in 285/435 (70%), moderate hypocapnia in 298/430 (69%), and severe hypotension in 270/435 (62%) cases. CONCLUSION: An objective method of comparing cases has been created with a method to automatically identify neonatal vital sign deviations. With further validation the method has the potential to be a powerful tool to drive future quality improvement projects in neonatal anesthesia. PMID- 27558534 TI - 4-Factor Prothrombin Complex Concentrate (PCC4, Kcentra(r)) Protocol Reduces Blood Requirements for Heart Transplantation: A Novel Protocol. AB - BACKGROUND All patients with a ventricular assist device (VAD) awaiting heart transplantation are anticoagulated with warfarin to prevent thromboembolism. The use of 4 factor prothrombin complex concentrate (PCC4, Kcentra(r)) for anticoagulation reversal prior to surgery may include benefits such as quicker reversal, longer duration of action, and a reduction in total volume of blood products used compared to other reversal practices. The study objective is to evaluate benefits of using an anticoagulation reversal protocol featuring PCC4, over standard of care in heart transplant patients requiring anticoagulation. MATERIAL AND METHODS This is a single center, combined retrospective and prospective, time-matched cohort study compared 12 patients transplanted pre protocol and 11 patients transplanted post-protocol. The primary outcome was the total volume of blood and blood products used. Secondary outcomes included length of hospital and ICU stay, safety and adverse events, primary chest closure, and a cost comparison. RESULTS The PCC4 reversal protocol showed a significant reduction in total blood volume received with an overall decrease of 1.76L (4.20L pre-protocol, 2.45L post-protocol, P=0.037), total units of blood products infused (20 units pre, 12 units post, P=0.033), and units of packed red blood cells (7 units pre, 3 units post, P=0.033). All heart transplant recipients were listed Status 1A with the primary indication being infection (n=12; 52%). Baseline characteristics, survival, and cost were not different between the two groups. There were no thrombotic events or patient that experienced serious reactions to PCC4. Secondary outcomes were only significant to time to INR reversal. CONCLUSIONS Patients treated with the PCC4 protocol demonstrated a significant decrease in volume of blood and units of blood products required prior to chest closure for heart transplant patients. PCC4 was found to be a safe and beneficial agent in anticoagulation reversal for patients on anticoagulation prior to heart transplantation. PMID- 27558537 TI - Cerebral cortex: Connecting with words. PMID- 27558535 TI - Cancer Diagnostics via Ultrasensitive Multiplexed Detection of Parathyroid Hormone-Related Peptides with a Microfluidic Immunoarray. AB - Parathyroid hormone-related peptide (PTHrP) is recognized as the major causative agent of humoral hypercalcemia of malignancy (HHM). The paraneoplastic PTHrP has also been implicated in tumor progression and metastasis of many human cancers. Conventional PTHrP detection methods like immunoradiometric assay (IRMA) lack the sensitivity required to measure target peptide levels prior to the development of hypercalcemia. In general, sensitive, multiplexed peptide measurement by immunoassay represents challenges that we address in this paper. We describe here the first ultrasensitive multiplexed peptide assay to measure intact PTHrP 1-173 as well as circulating N-terminal and C-terminal peptide fragments. This versatile approach should apply to almost any collection of peptides that are long enough to present binding sites for two antibodies. To target PTHrP, we employed a microfluidic immunoarray featuring a chamber for online capture of the peptides from serum onto magnetic beads decorated with massive numbers of peptide specific antibodies and enzyme labels. Magnetic bead-peptide conjugates were then washed and sent to a detection chamber housing an antibody-modified 8-electrode array fabricated by inkjet printing of gold nanoparticles. Limits of detection (LODs) of 150 aM (~1000-fold lower than IRMA) in 5 MUL of serum were achieved for simultaneous detection of PTHrP isoforms and peptide fragments in 30 min. Good correlation for patient samples was found with IRMA (n = 57); r(2) = 0.99 assaying PTHrP 1-86 equiv fragments. Analysis by a receiver operating characteristic (ROC) plot gave an area under the curve of 0.96, 80-83% clinical sensitivity, and 96-100% clinical specificity. Results suggest that PTHrP1-173 isoform and its short C-terminal fragments are the predominant circulating forms of PTHrP. This new ultrasensitive, multiplexed assay for PTHrP and fragments is promising for clinical diagnosis, prognosis, and therapeutic monitoring from early to advanced stage cancer patients and to examine underlying mechanisms of PTHrP overproduction. PMID- 27558538 TI - Tribute to J. Andrew McCammon. PMID- 27558539 TI - Autobiography of J. Andrew McCammon. PMID- 27558540 TI - Colleagues of J. Andrew McCammon. PMID- 27558536 TI - Emerging roles of GluN3-containing NMDA receptors in the CNS. AB - GluN3-containing NMDA receptors (GluN3-NMDARs) are rarer than the 'classical' NMDARs, which are composed solely of GluN1 and GluN2 subunits, and have non conventional biophysical, trafficking and signalling properties. In the CNS, they seem to have important roles in delaying synapse maturation until the arrival of sensory experience and in targeting non-used synapses for pruning. The reactivation of GluN3A expression at inappropriate ages may underlie maladaptive synaptic rearrangements observed in addiction, neurodegenerative diseases and other major brain disorders. Here, we discuss current evidence for these and other emerging roles for GluN3-NMDARs in the physiology and pathology of the CNS. PMID- 27558542 TI - Selected Publications of J. Andrew McCammon. PMID- 27558541 TI - Abbreviated Curriculum Vitae of J. Andrew McCammon. PMID- 27558543 TI - Polycomb-group protein SlMSI1 represses the expression of fruit-ripening genes to prolong shelf life in tomato. AB - Polycomb-group (PcG) protein MULTICOPY SUPPRESSOR OF IRA1 (MSI1) protein is an evolutionarily conserved developmental suppressor and plays a crucial role in regulating epigenetic modulations. However, the potential role and function of MSI1 in fleshy fruits remain unknown. In this study, SlMSI1 was cloned and transformed into tomato to explore its function. The quantitative real-time PCR results showed that SlMSI1 was highly expressed in flowers and fruits and that its transcript and protein levels were significantly decreased in fruits after the breaker stage. Additionally, SlMSI1-overexpressing transgenic tomatoes displayed abnormal non-ripening fruit formation, whereas its suppression promoted fruit ripening in transgenic tomatoes. Quantitative real-time PCR assays also showed that RIN and its regulons were decreased in SlMSI1 overexpression transgenic tomato fruits. Furthermore, RNA-seq analysis demonstrated that SlMSI1 inhibits fruit ripening by negatively regulating a large set of fruit-ripening genes in addition to RIN and its regulons. Finally, genetic manipulation of SlMSI1 and RIN successfully prolonged the fruit shelf life by regulating the fruit-ripening genes in tomato. Our findings reveal a novel regulatory function of SlMSI1 in fruit ripening and provide a new regulator that may be useful for genetic engineering and modification of fruit shelf life. PMID- 27558545 TI - The value of patient reporting to the pharmacovigilance system: a systematic review. AB - AIMS: Current trends in pharmacovigilance systems are veering towards patient involvement in spontaneous reporting of adverse drug reactions (ADRs). The aim of the current systematic review was to identify what is known and what remains unknown with respect to patient reporting to pharmacovigilance systems. METHODS: A systematic literature search was conducted in PubMed, CINAHL, Journals@Ovid and the Cochrane Library. Studies were included if they contained: (i) reviews about patient reporting; (ii) evaluation of patient reports to national or supranational pharmacovigilance authorities; (iii) a comparison between patient and healthcare professional (HCP) reports submitted to pharmacovigilance authorities; and (iv) surveys of patient experiences, opinions and awareness about reporting ADRs. The methodological quality of the studies was assessed according to principles of Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: A total of thirty four studies were included. Five of the studies were reviews (two of which systematic reviews), fourteen retrospective observational studies, nine surveys and six applied mixed research methods. Patient reporting has the advantages of bringing novel information about ADRs. It provides a more detailed description of ADRs, and reports about different drugs and system organ classes when compared with HCP reporting. In addition, patients describe the severity and impact of ADRs on daily life, complementing information derived from HCPs. Patient reporting is relatively rare in most countries. CONCLUSIONS: Patient reporting adds new information, and perspective about ADRs in a way otherwise unavailable. This can contribute to better decision-making processes in regulatory activities. The present review identified gaps in knowledge that should be addressed to improve our understanding of the full potential and drawbacks of patient reporting. PMID- 27558544 TI - Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress. AB - KEY POINTS: Hyperammonaemia occurs in hepatic, cardiac and pulmonary diseases with increased muscle concentration of ammonia. We found that ammonia results in reduced skeletal muscle mitochondrial respiration, electron transport chain complex I dysfunction, as well as lower NAD+ /NADH ratio and ATP content. During hyperammonaemia, leak of electrons from complex III results in oxidative modification of proteins and lipids. Tricarboxylic acid cycle intermediates are decreased during hyperammonaemia, and providing a cell-permeable ester of alphaKG reversed the lower TCA cycle intermediate concentrations and increased ATP content. Our observations have high clinical relevance given the potential for novel approaches to reverse skeletal muscle ammonia toxicity by targeting the TCA cycle intermediates and mitochondrial ROS. ABSTRACT: Ammonia is a cytotoxic metabolite that is removed primarily by hepatic ureagenesis in humans. Hyperammonaemia occurs in advanced hepatic, cardiac and pulmonary disease, and in urea cycle enzyme deficiencies. Increased skeletal muscle ammonia uptake and metabolism are the major mechanism of non-hepatic ammonia disposal. Non-hepatic ammonia disposal occurs in the mitochondria via glutamate synthesis from alpha ketoglutarate resulting in cataplerosis. We show skeletal muscle mitochondrial dysfunction during hyperammonaemia in a comprehensive array of human, rodent and cellular models. ATP synthesis, oxygen consumption, generation of reactive oxygen species with oxidative stress, and tricarboxylic acid (TCA) cycle intermediates were quantified. ATP content was lower in the skeletal muscle from cirrhotic patients, hyperammonaemic portacaval anastomosis rat, and C2C12 myotubes compared to appropriate controls. Hyperammonaemia in C2C12 myotubes resulted in impaired intact cell respiration, reduced complex I/NADH oxidase activity and electron leak occurring at complex III of the electron transport chain. Consistently, lower NAD+ /NADH ratio was observed during hyperammonaemia with reduced TCA cycle intermediates compared to controls. Generation of reactive oxygen species resulted in increased content of skeletal muscle carbonylated proteins and thiobarbituric acid reactive substances during hyperammonaemia. A cell-permeable ester of alpha-ketoglutarate reversed the low TCA cycle intermediates and ATP content in myotubes during hyperammonaemia. However, the mitochondrial antioxidant MitoTEMPO did not reverse the lower ATP content during hyperammonaemia. We provide for the first time evidence that skeletal muscle hyperammonaemia results in mitochondrial dysfunction and oxidative stress. Use of anaplerotic substrates to reverse ammonia-induced mitochondrial dysfunction is a novel therapeutic approach. PMID- 27558546 TI - Understanding music with cochlear implants. AB - Direct stimulation of the auditory nerve via a Cochlear Implant (CI) enables profoundly hearing-impaired people to perceive sounds. Many CI users find language comprehension satisfactory, but music perception is generally considered difficult. However, music contains different dimensions which might be accessible in different ways. We aimed to highlight three main dimensions of music processing in CI users which rely on different processing mechanisms: (1) musical discrimination abilities, (2) access to meaning in music, and (3) subjective music appreciation. All three dimensions were investigated in two CI user groups (post- and prelingually deafened CI users, all implanted as adults) and a matched normal hearing control group. The meaning of music was studied by using event related potentials (with the N400 component as marker) during a music-word priming task while music appreciation was gathered by a questionnaire. The results reveal a double dissociation between the three dimensions of music processing. Despite impaired discrimination abilities of both CI user groups compared to the control group, appreciation was reduced only in postlingual CI users. While musical meaning processing was restorable in postlingual CI users, as shown by a N400 effect, data of prelingual CI users lack the N400 effect and indicate previous dysfunctional concept building. PMID- 27558547 TI - Bioassimilable sulphur provides effective control of Oidium neolycopersici in tomato, enhancing the plant immune system. AB - BACKGROUND: Developments of alternatives to the use of chemical pesticides to control pests are focused on the induction of natural plant defences. The study of new compounds based on liquid bioassimilable sulphur and its effect as an inductor of the immune system of plants would provide an alternative option to farmers to enhance plant resistance against pathogen attacks such as powdery mildew. In order to elucidate the efficacy of this compound in tomato against powdery mildew, we tested several treatments: curative foliar, preventive foliar, preventive in soil drench and combining preventive in soil drench and curative foliar. RESULTS: In all cases, treated plants showed lower infection development, better physiological parameters and a higher level of chlorophyll. We also observed better performance in parameters involved in plant resistance such as antioxidant response, callose deposition and hormonal levels. CONCLUSION: The results indicate that preventive and curative treatments can be highly effective for the prevention and control of powdery mildew in tomato plants. Foliar treatments are able to stop the pathogen development when they are applied as curative. Soil drench treatments induce immune response mechanisms of plants, increasing significantly callose deposition and promoting plant development. (c) 2016 Society of Chemical Industry. PMID- 27558548 TI - Evidence-based (S3) guidelines for diagnostics and treatment of venous leg ulcers. PMID- 27558550 TI - Right Ventricular Pressure Overload and Pathophysiology of Growing Porcine Biomodel. AB - The primary objective was to create a clinically relevant model of right ventricular hypertension and to study right ventricular myocardial pathophysiology in growing organism. The secondary objective was to analyse the effect of oral enoximone (phosphodiesterase inhibitor) therapy on right ventricular haemodynamic parameters and myocardial changes in biomodel of right ventricular hypertension. The study included a total of 12 piglets of 42 days of age. Under general anaesthesia, pulmonary artery banding (PAB) was performed surgically to constrict the main pulmonary artery to about 70-80 % of its original dimension. The study presented two groups of animals labelled C (control animals with PAB; n = 8) and E (animals with PAB and oral administration of enoximone; n = 4). Direct pressure and echocardiographic measurements were taken during operation (time-1), and again at 40 days after surgery (time-2). The animals were killed, and tissue samples from the heart chambers were collected for quantitative morphological assessment. Statistical analysis was performed on all acquired data. At time-2, the median weight of animals doubled and the median systolic pressure gradient across the PAB increased (46.59 +/- 15.87 mmHg vs. 20.29 +/- 5.76 mmHg; p < 0.001). Changes in haemodynamic parameters were compatible with right ventricular diastolic dysfunction in all the animals. Apoptosis, tissue proliferation and fibrosis were identified in all the myocardial tissue samples. Right ventricular pressure overload leads to increased apoptosis of cardiac myocytes, proliferation and myocardial fibrosis. Our study did not show evidence of haemodynamic benefit or myocardial protective effect of oral enoximone treatment. PMID- 27558551 TI - Doppler Flow Pattern and Arterial Stiffness in Patients with Aortic Coarctation. AB - Patients with aortic coarctation (CoAo) often have a diastolic flow in the descending aorta. The effect of arterial stiffness on CoAo flow pattern was described in vitro and with computer models. Study of Doppler flow patterns and arterial stiffness may provide helpful data to support the decision of CoAo treatment. Fifty studies were obtained in 31 patients (14 women, 21.5 +/- 15.5 years). In 19 patients, studies were performed before and after percutaneous intervention. Systolic invasive gradients were measured (Sgrad). Doppler parameters included Doppler corrected gradient (Dgrad), diastolic velocity at end of T wave (DVT), end diastolic velocity (DVQ), systolic and diastolic half pressure times (SHPTc and DHPTc) and velocity runoff (VRc). In 19 patients, before intervention, arterial stiffness was assessed by measuring pulsed wave velocity (PWV) between right carotid and radial arteries. Sgrad showed correlation with Dgrad, DVT, DVQ, SHPTc, DHPTc and VRc (p < 0.01). Using multiple regression models, Sgrad variability was best explained by combining the variables Dgrad and DHPTc (R 2 = 0.766). A variable named DTail was obtained with DTail = 1 if DHPTc > 0. In the group with Sgrad below 30 mmHg, a negative correlation was found between DTail and PWV (p = 0.024), suggesting that low aortic stiffness contributes to persistent diastolic flow in the descending aorta. Doppler systolic and diastolic parameters correlated well with severity of CoAo. In mild to moderate CoAo, Doppler diastolic flow in the descending aorta was more likely in patients with lower arterial stiffness. PMID- 27558552 TI - Association of A Dilated Coronary Sinus in the Fetus with Actual and Apparent Coarctation of the Aorta and Diminutive Left Heart Structures. AB - Evidence suggests an association between left heart obstructive lesions and dilated coronary sinus (DCS), but this has not been studied in fetuses. A retrospective review of fetal echocardiograms (FE) over an 8-year period was conducted, and patients with DCS were identified and confirmed postnatally. There were 5840 FE performed on 4920 women during this period. Of 49 patients with DCS, 22 had normal intracardiac anatomy and 27 patients had congenital heart disease (CHD) yielding an incidence of 4.6 % in the presence of CHD (27/584). Of 27 patients with DCS and CHD, approximately a third had either hypoplastic left ventricles and/or coarctations (10/27, 37 %). The incidence of left heart obstructive lesions was much higher in the presence of a DCS (37 % vs 45/557, 8 %, p < 0.0001). The odds ratio of left heart hypoplasia in fetuses with CHD and a DCS was 6.6 (95 % CI 2.8-15.3). Comparison of patients with postnatally confirmed coarctation with those with normal intracardiac anatomy with DCS, revealed that in the former, the right ventricle (p = 0.005), pulmonic valve annulus (p = 0.0001) and the tricuspid inflow were larger (p = 0.001) compared to corresponding left-sided structures. The size of the DCS was not significantly different between the two groups, but in the former, the DCS was more closely related to the posterior leaflet of the mitral valve and caused a significant diminution of the mitral inflow. Our study suggests a strong association, possibly causal, between left heart obstructive lesions and DCS in utero. PMID- 27558553 TI - Center Variability in Timing of Stage 2 Palliation and Association with Interstage Mortality: A Report from the National Pediatric Cardiology Quality Improvement Collaborative. AB - For infants with single-ventricle lesions with aortic arch hypoplasia, the interstage period from discharge following stage 1 palliation (S1P) until stage 2 palliation (S2P) remains high risk. Significant variability among institutions exists around the timing of S2P. We sought to describe institutional variation in timing of S2P, determine the association between timing of S2P and interstage mortality, and determine the impact of earlier S2P on hospital morbidity and mortality. The National Pediatric Cardiology Quality Improvement Collaborative registry was queried. Centers were divided based on median age at S2P into early (n = 15) and late (n = 16) centers using a cutoff of 153 days. Groups were compared using Chi-squared or Wilcoxon rank-sum test. Multivariable logistic regression was used to determine risk factors for interstage mortality. The final cohort included 789 patients from 31 centers. There was intra- and inter-center variability in timing of S2P, with the median age by center ranging from 109 to 214 days. Late centers had a higher mortality (9.9 vs. 5.7 %, p = 0.03) than early centers. However, the event rate (late: 8.2 vs. early: 5.8 deaths per 10,000 interstage days) was not different by group (p = 0.26). Survival to hospital discharge and hospital length of stay following S2P were similar between groups. In conclusion, in a large multi-institution collaborative, the median age at S2P varies among centers. Although optimal timing of S2P remains unclear, centers performing early S2P did not experience worse S2P outcomes and experienced less interstage mortality. PMID- 27558555 TI - Erratum to: Nonlinear viscoelastic characterization of bovine trabecular bone. PMID- 27558554 TI - Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential. AB - Aneuploidy leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem (ES) cells by generating a series of cell lines that each carries an extra copy of single chromosomes, including trisomy 6, 8, 11, 12, or 15. Most of these aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self-renewal and showed a reduced capacity to differentiate in vitro Moreover, trisomic stem cells formed teratomas more efficiently, from which undifferentiated cells can be recovered. Further investigations demonstrated that co-culture of wild-type and aneuploid ES cells or supplementation with extracellular BMP4 rescues the differentiation defects of aneuploid ES cells. PMID- 27558556 TI - Bibliometric trends of health economic evaluation in Sub-Saharan Africa. AB - BACKGROUND: Collaboration between Sub-Saharan African researchers is important for the generation and transfer of health technology assessment (HTA) evidence, in order to support priority-setting in health. The objective of this analysis was to evaluate collaboration patterns between countries. METHODS: We conducted a rapid evidence assessment that included a random sample of health economic evaluations carried out in 20 countries (Angola, Botswana, Congo, Lesotho, Madagascar, Malawi, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Swaziland, Tanzania, Zambia, Zimbabwe, Ghana, Kenya, Nigeria, Ethiopia, Uganda). We conducted bibliometric network analysis based on all first authors with a Sub Saharan African academic affiliation and their co-authored publications ("network articles"). Then we produced a connection map of collaboration patterns among Sub Saharan African researchers, reflecting the number of network-articles and the country of affiliation of the main co-authors. RESULTS: The sample of 119 economic evaluations mostly related to treatments of communicable diseases, in particular HIV/AIDS (42/119, 35.29 %) and malaria (26/119, 21.85 %). The 39 first authors from Sub-Saharan African institutions together co-authored 729 network articles. The network analysis showed weak collaboration between health economic researchers in Sub-Saharan Africa, with researchers being more likely to collaborate with Europe and North America than with other African countries. South Africa stood out as producing the highest number of health economic evaluations and collaborations. CONCLUSIONS: The development and evaluation of HTA research networks in Sub-Saharan Africa should be supported, with South Africa central to any such efforts. Organizations and institutions from high income countries interested in supporting priority setting in Sub-Saharan Africa should include promoting collaboration as part of their agendas, in order to take advantage of the potential transferability of results and methods of the available health economic analyses in Africa and internationally. PMID- 27558557 TI - Targeting cytokine signaling in salt-sensitive hypertension. AB - Activated immune cell populations contribute to hypertension in part through inciting damage to the kidney and by provoking inappropriate sodium reabsorption in the nephron. Inflammatory mediators called cytokines produced by T lymphocytes and macrophages act on specific sodium transporters in the kidney, augmenting their activity or expression, with consequent expansion of intravascular fluid volume and cardiac output. The overlapping functions of these cytokines, each of which may activate multiple receptors, present challenges in precisely targeting inflammatory signaling cascades in hypertension. Moreover, broad immune suppression could expose the hypertensive patient to disproportional risks of infection or malignancy. Nevertheless, the possibility that incisive immunomodulatory therapies could provide cardiovascular and renal protection through both blood pressure-dependent and -independent mechanisms justifies comprehensive investigation into the relevant signaling pathways and tissue sites in which inflammatory cytokines function to exaggerate blood pressure elevation and target organ damage in hypertension. PMID- 27558559 TI - Age-dependent shifts in renal response to injury relate to altered BMP6/CTGF expression and signaling. AB - Age is associated with an increased prevalence of chronic kidney disease (CKD), which, through progressive tissue damage and fibrosis, ultimately leads to loss of kidney function. Although much effort is put into studying CKD development experimentally, age has rarely been taken into account. Therefore, we investigated the effect of age on the development of renal tissue damage and fibrosis in a mouse model of obstructive nephropathy (i.e., unilateral ureter obstruction; UUO). We observed that after 14 days, obstructed kidneys of old mice had more tubulointerstitial atrophic damage but less fibrosis than those of young mice. This was associated with reduced connective tissue growth factor (CTGF), and higher bone morphogenetic protein 6 (BMP6) expression and pSMAD1/5/8 signaling, while transforming growth factor-beta expression and transcriptional activity were no different in obstructed kidneys of old and young mice. In vitro, CTGF bound to and inhibited BMP6 activity. In summary, our data suggest that in obstructive nephropathy atrophy increases and fibrosis decreases with age and that this relates to increased BMP signaling, most likely due to higher BMP6 and lower CTGF expression. PMID- 27558560 TI - Interorgan handling of fibroblast growth factor-23 in humans. AB - Fibroblast growth factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms that regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs, and lung in 11 patients [estimated glomerular filtration rate (eGFR) 60 +/- 6 ml/min] during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ~22%. The FE of FGF-23 across the kidney was similar to that of creatinine (~17%, P = NS). In addition, the FGF-23 FE by the kidney was significantly directly related to eGFR (r = 0.709 P = 0.018) and to kidney creatinine FE (r = 0.736 P = 0.013) but only as a trend to plasma phosphate levels (r = 0.55, P = 0.18). There was no difference in FGF-23 levels in blood perfusing splanchnic organs and cardiopulmonary bed. However, the arterial-venous difference of FGF-23 across the lung was directly related to FGF 23 pulmonary artery levels, suggesting that the lung, and possibly the heart, participate in the homeostasis of plasma FGF-23 when its systemic levels are increased. Our data show that the human kidney is the only site for FGF-23 removal from blood and suggest that FGF-23 is predominantly removed by glomerular filtration. The kidney ability to remove FGF-23 from the circulation likely accounts for the early increase in blood of FGF-23 in patients with CKD. PMID- 27558561 TI - Environmental hit on a genetic basis in polycystic kidney disease. PMID- 27558562 TI - The vasopressin type 2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMP-independent pathway. AB - Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7 transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be cAMP dependent. However, on the basis of recent reports, it was hypothesized in the current study that increased cAMP levels are not necessary for AQP2 membrane targeting. The role and dynamics of cAMP signaling in AQP2 membrane targeting in Madin-Darby canine kidney and mouse cortical collecting duct (mpkCCD14) cells was examined using selective agonists against the V2R (dDAVP), EP2 (butaprost), and EP4 (CAY10580). During EP2 stimulation, AQP2 membrane targeting continually increased during 80 min of stimulation; whereas cAMP levels reached a plateau after 10 min. EP4 stimulation caused a rapid and transient increase in AQP2 membrane targeting, but did not significantly increase cAMP levels. After washout of the EP2 agonist or dDAVP, AQP2 membrane abundance remained elevated for at least 80 min, whereas cAMP levels rapidly decreased. Similar effects of the EP2 agonist were also observed for AQP2 constitutively nonphosphorylated at ser-269. The adenylyl cyclase inhibitor SQ22536 did not prevent AQP2 targeting during stimulation of each receptor, nor after dDAVP washout. In conclusion, this study demonstrates that although direct stimulation with cAMP causes AQP2 membrane targeting, cAMP is not necessary for receptor-mediated AQP2 membrane targeting and Gs-coupled receptors can also signal through an alternative pathway that increases AQP2 membrane targeting. PMID- 27558563 TI - Assessment of Perceived Stress Related to Migration and Acculturation in Patients with Psychiatric Disorders (MIGSTR10)-Development, Reliability, and Dimensionality of a Brief Instrument. AB - Assessment of stressors related to migration and acculturation in patients with psychiatric disorder and migration background could help improve culturally sensitive concepts of psychiatry and psychotherapy for diagnosis and treatment. The present overview delineates development and psychometric properties of an instrument (MIGSTR10) for assessment of stressors related to migration and acculturation, particularly for application in patients with psychiatric disorders. Ten migration-related stressors were derived from a qualitative content analysis of case histories of patients with psychiatric disorder and migration background and put into a suitable interview and questionnaire format (MIGSTR10; 10 questions, answer format: categorical yes/no, and dimensional 0-10) for self-assessment and observer ratings in several languages. Reliability (interrater agreement, internal consistency) and dimensionality (multi dimensional scaling, MDS) were investigated in n = 235 patients with migration background and n = 612 indigenous German patients. Interrater agreement (ICC) for MIGSTR10 single items and sum scores (categorical and dimensional) was sufficiently high (>=.58); internal consistency (Cronbach's alpha) reached medium to high values (.56-.73). MDS revealed a two-dimensional solution with two item clusters (A: communication, migration history, forced marriage, homesickness, discrimination, other stressors; B: family conflicts, loss of status, feelings of shame, guilt feelings). The MIGSTR10 is a rationally developed, straightforward 10-item screening instrument with satisfactory psychometric properties for the assessment of individual and specific stressors related to migration and acculturation. PMID- 27558558 TI - Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. AB - Increasing incidences of obesity and diabetes have made diabetic kidney disease (DKD) the leading cause of chronic kidney disease and end-stage renal disease worldwide. Despite current pharmacological treatments, including strategies for optimizing glycemic control and inhibitors of the renin-angiotensin system, DKD still makes up almost one-half of all cases of end-stage renal disease in the United States. Compelling and mounting evidence has clearly demonstrated that immunity and inflammation play a paramount role in the pathogenesis of DKD. This article reviews the involvement of the immune system in DKD and identifies important roles of key immune and inflammatory mediators. One of the most recently identified biomarkers is serum amyloid A, which appears to be relatively specific for DKD. Novel and evolving treatment approaches target protein kinases, transcription factors, chemokines, adhesion molecules, growth factors, advanced glycation end-products, and other inflammatory molecules. This is the beginning of a new era in the understanding and treatment of DKD, and we may have finally reached a tipping point in our fight against the growing burden of DKD. PMID- 27558564 TI - Molecular Evidence for the Aerial Route of Infection of Mycobacterium leprae and the Role of Asymptomatic Carriers in the Persistence of Leprosy. AB - BACKGROUND: Leprosy persists as a public health problem. The chain of transmission and mechanism of infection are not completely understood. In the current study, we investigated the route of infection and of disease onset, from airway exposure, colonization, and bloodstream dissemination. METHODS: Mycobacterium leprae DNA was detected through quantitative polymerase chain reaction in nasal vestibule, nasal turbinate mucosa, and peripheral blood samples, along with anti-phenolic glycolipid I serology and skin tests from the same individual, from 113 leprosy patients and 104 household contacts of patients (HHCs). Bivariate statistics and multiple correspondence analysis were employed. RESULTS: The rates of DNA positivity among patients were 66.4% (75 of 113) for nasal swab samples, 71.7% (81 of 113) for nasal turbinate biopsy samples, 19.5% (22 of 113) for blood samples, with seropositivity of 62.8% (71 of 113 samples) and with increasing incidences toward the multibacillary pole of the clinical spectrum. Positivity among HHCs were as follows: 49% (51 of 104) for nasal swab samples, 53.8% (56 of 104) for nasal biopsy samples, 6.7% (7 of 104) for blood samples, and 18.3% (19 of 104 samples) for anti-phenolic glycolipid I serology. During the follow-up of 5-7 years, out of 104 HHCs, 7 developed leprosy (6.7%). Risk for the disease outcome was estimated by comparing results in HHCs who develop leprosy with those not affected. Neither nasal passage nor mucosa positivity was determinant of later disease onset; however, blood presence increased the risk for disease development (relative risk/positive likelihood ratio, 5.54; 95% confidence interval, 1.30-23.62), as did seropositivity (positive likelihood ratio, 3.69 [1.67-8.16]; relative risk, 5.97 [1.45-24.5]). CONCLUSIONS: Our findings strongly suggest that the aerosol route of infection and transmission is predominant and that HHCs contribute to the infection risk to themselves and probably to others. PMID- 27558565 TI - The Importance of Scientific Debate in the Identification, Containment, and Control of Artemisinin Resistance. PMID- 27558566 TI - Editorial Commentary: Evidences of Aerial Route of Mycobacterium leprae Infection and Doubts About Transmission and Natural Protection in Leprosy. PMID- 27558567 TI - Editorial Commentary: Drug-Resistance in Leprosy: Moving Toward Understanding the Scope of the Problem and How to Tackle It. PMID- 27558568 TI - Transmission of Drug-Resistant Leprosy in Guinea-Conakry Detected Using Molecular Epidemiological Approaches. AB - Molecular drug susceptibility testing was performed on skin biopsies from 24 leprosy patients from Guinea-Conakry for the first time. We identified primary drug resistance in 4 cases and a dapsone-resistant cluster caused by the same strain. Primary transmission of drug-resistant Mycobacterium leprae, including a rifampicin-resistant strain, is reported. PMID- 27558569 TI - Editorial Commentary: Can We Afford to Control the HIV Epidemic With Antiretrovirals? Can We Afford Not to Do So? PMID- 27558570 TI - Individualized Approaches Are Needed for Optimized Blood Cultures. AB - Many strategies and technologies are available to improve blood culture (BC) based diagnostics. The ideal approach to BCs varies between healthcare institutions. Institutions need to examine clinical needs and practices in order to optimize BC-based diagnostics for their site. Before laboratories consider offering rapid matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) or expensive rapid panel-based molecular BC diagnostics, they should optimize preanalytical, analytical, and postanalytical processes and procedures surrounding BC systems. Several factors need to be considered, including local resistance rates, antibiotic prescribing patterns, patient- and provider-types, laboratory staffing, and personnel available to liaise with clinicians to optimize antibiotic use. While there is much excitement surrounding new high-technology diagnostics, cost-neutral benefits can be realized by optimizing existing strategies and using available tools in creative ways. Rapid BC diagnostics should be implemented in a manner that optimizes impact. Strategies to optimize these BC diagnostics in individual laboratories are presented here. PMID- 27558571 TI - A Cost-effectiveness Analysis of Preexposure Prophylaxis for the Prevention of HIV Among Los Angeles County Men Who Have Sex With Men. AB - BACKGROUND: Substantial gaps remain in understanding the trade-offs between the costs and benefits of choosing alternative human immunodeficiency virus (HIV) prevention strategies, including test-and-treat (expanded HIV testing combined with immediate treatment) and PrEP (initiation of preexposure prophylaxis by high risk uninfected individuals) strategies. METHODS: We develop a mathematical epidemiological model to simulate HIV incidence among men residing in Los Angeles County, California, aged 15-65 years, who have sex with men. We combine these incidence data with an economic model to estimate the discounted cost, effectiveness (quality-adjusted life-years [QALYs]), and incremental cost effectiveness ratios of various HIV prevention strategies using a societal perspective and a lifetime horizon. RESULTS: PrEP and test-and-treat yield the largest reductions in HIV incidence, and are highly cost-effective ($27 863/QALY and $19 302/QALY, respectively) relative to status quo and at a US willingness-to pay threshold of $150 000/QALY saved. Status quo and 12 test-and-treat and PrEP strategies determine the frontier for efficient decisions. More aggressive strategies are costlier, but more effective, albeit with diminishing returns. The relative effectiveness of PrEP is sensitive to the initial HIV prevalence rate, PrEP and antiretroviral therapy (ART) adherence and initiation rates, the probabilities of HIV transmission, and the rates of sexual partner mixing. CONCLUSIONS: PrEP and test-and-treat offer cost-effective alternatives to the status quo. The success of these strategies depends on ART and PrEP adherence and initiation rates. The lack of evidence on adherence behaviors toward PrEP, therefore, warrants further studies. PMID- 27558572 TI - A Comparison Study Between Point-of-Care Testing Systems and Central Laboratory for Determining Blood Glucose in Venous Blood. AB - BACKGROUND: Diabetes mellitus is a metabolic disease that is characterized by hyperglycemia. Blood glucose (BG) is helpful for the diagnosis and treatment of diabetes and an important part of the management of diabetes. Point-of-care testing (POCT) is generally used by patients themselves or medical personnel to monitor BG. The objective of this article was to evaluate the accuracy and consistency of POCT on venous blood samples and compare it with the central laboratory system to determine the reliability of POCT measurement results as diagnostic criteria. METHOD: A total of 162 venous whole blood samples were pooled in this study, which included different concentrations and were determined by three POCT systems randomly. The results were compared with the central laboratory system, which uses the Glucose GOD-PAP method (HITACHI 7600-120). The accuracy was evaluated by the International Organization for Standardization (ISO) 15197:2013. RESULT: Bland-Altman and Passing-Bablok regression analysis showed three POCT systems that were comparable with the reference method (0.65, 95% CI: -0.57 to 1.86, Y = -0.11 + 0.95X for ACCU-CHEK(r) Performa; 0.40, 95% CI: -1.3 to 2.1, Y = 0.036 + 0.96X for ACCU-CHEK(r) Active; 0.70, 95% CI: -0.44 to 1.83, Y = -0.073 + 0.95X for OneTouch (r) UltraVue). According to ISO 15197:2013, all POCT systems showed 100% of the results within 0.83 mmol/l (15 mg/dl) at BG concentrations <5.55 mmol/l (100 mg/dl); 92%, 89.2%, and 95.7% of the measurement results within 15% at BG concentrations >=5.55 mmol/l (100 mg/dl) for ACCU CHEK(r) Performa, ACCU-CHEK(r) Active, and OneTouch(r) UltraVue, respectively. CONCLUSIONS: The POCT system cannot replace the central laboratory system as a provider of a standard result in clinical diagnosis. It can only be used as a screening test. PMID- 27558573 TI - Do we underestimate the predictive value of the ulnar styloid involvement in distal radius fractures? A systematic review and meta-analysis of clinical studies. PMID- 27558574 TI - Release of adhesions after zone II flexor tendon repair: the 'Gigli suture' technique. PMID- 27558576 TI - A Gold Standard to Accurately Assess Vitamin A Status: Are We There Yet? PMID- 27558575 TI - Disease characteristics and prognosis of myelodysplastic syndrome presenting with isolated thrombocytopenia. AB - Patients with myelodysplastic syndrome (MDS) who present with isolated thrombocytopenia (TCP) constitute a poorly described subgroup. The aim of the present study was to retrospectively evaluate disease characteristics and prognosis in patients with MDS and isolated TCP at a tertiary care center. Fifty patients (12 %) had isolated thrombocytopenia as the first presentation of MDS. Patients had varying MDS sub-classifications and cytogenetic profiles. The most common IPSS-R risk score was low (n = 24), although half of the patients had either IPSS-R intermediate (n = 18), high or very high risk disease (n = 7). Leukemic transformation occurred in 10 patients and there were 14 deaths (28 %) amongst all IPSS-R risk scores. Therapeutic agents used in this patient subgroup included hypomethylating agents and thrombopoietin receptor agonists. Overall, MDS with isolated TCP did not appear to have an inherently indolent course, as has been suggested previously. Future studies are needed to improve risk stratification, identify relevant contributors to disease pathogenesis, and better define treatment modalities. PMID- 27558577 TI - High-Dose Monthly Maternal Cholecalciferol Supplementation during Breastfeeding Affects Maternal and Infant Vitamin D Status at 5 Months Postpartum: A Randomized Controlled Trial. AB - BACKGROUND: Many countries recommend daily infant vitamin D supplementation during breastfeeding, but compliance is often poor. A monthly, high-dose maternal regimen may offer an alternative strategy, but its efficacy is unknown. OBJECTIVE: The objective of the study was to determine the effect of 2 different monthly maternal doses of cholecalciferol on maternal and infant 25 hydroxyvitamin D [25(OH)D] status during the first 5 mo of breastfeeding. METHODS: With the use of a randomized, double-blind, placebo-controlled design, women who were planning to exclusively breastfeed for 6 mo (n = 90; mean age: 32.1 y; 71% exclusively breastfeeding at week 20) were randomly assigned to receive either cholecalciferol (50,000 or 100,000 IU) or a placebo monthly from week 4 to week 20 postpartum. The treatment effects relative to placebo were estimated as changes in maternal and infant serum 25(OH)D from baseline to week 20 postpartum by using a linear fixed-effects regression model. Additional secondary analyses, adjusted for potential confounders such as season of birth, vitamin D-fortified formula intake, and infant or maternal skin color, were also conducted. RESULTS: After 16 wk of supplementation, changes in maternal serum 25(OH)D were significantly higher in the 50,000-IU/mo (12.8 nmol/L; 95% CI: 0.4, 25.2 nmol/L) and 100,000-IU/mo (21.5 nmol/L; 95% CI: 9.2, 33.8 nmol/L) groups than in the placebo group (P = 0.43 and P < 0.001, respectively). For infants, the unadjusted mean changes in serum 25(OH)D were 4.5 nmol/L (95% CI: -16.2, 25.0 nmol/L) for the 50,000-IU/mo group and 15.8 nmol/L (95% CI: -4.7, 36.4 nmol/L) for the 100,000-IU/mo group, but the changes did not differ from the placebo reference group. However, after adjustment for season of birth, vitamin D fortified formula intake, and infant skin color, the mean change effect size for the 100,000-IU/mo group was 19.1 nmol/L (95% CI: 2.5, 35.6 nmol/L; P = 0.025) higher than that in the placebo group. CONCLUSIONS: Maternal cholecalciferol supplementation at a dose of 100,000 IU/mo during the first 5 mo of breastfeeding potentially benefits infant vitamin D status. Further studies are required to determine optimum dose and dosing frequency. This trial was registered at www.anzctr.org.au as ACTRN12611000108910. PMID- 27558578 TI - Minerals and Trace Elements in Human Breast Milk Are Associated with Guatemalan Infant Anthropometric Outcomes within the First 6 Months. AB - BACKGROUND: Breast milk is the recommended source of nutrients for infant growth, but its adequacy to meet infants' mineral and trace element needs is unknown. OBJECTIVES: We used breast-milk mineral and trace element concentrations of Guatemalan mothers at 3 lactation stages to estimate total daily intakes and to determine whether intakes were associated with early infant growth. METHODS: In this cross-sectional study, breast-milk samples were collected from Mam-Mayan mothers during transitional (5-17 d, n = 56), early (18-46 d, n = 75), and established (4-6 mo, n = 103) lactation; z scores for weight (WAZ), length (LAZ), and head circumference (HCAZ) were measured. Concentrations of 11 minerals (calcium, potassium, magnesium, sodium, copper, iron, manganese, rubidium, selenium, strontium, and zinc) were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). WHO equations were used to calculate the estimated energy requirement, which was divided by the energy density of breast milk to estimate daily milk volume, and this number was multiplied by breast-milk mineral concentrations to estimate intakes. Principal component analyses identified clusters of minerals; principal components (PCs) were used in regression analyses for anthropometric outcomes. RESULTS: Estimated breast-milk intakes during established lactation were insufficient to compensate for the lower milk sodium, copper, manganese, and zinc concentrations in male infants and the lower sodium, iron and manganese concentrations in female infants. Estimated intakes of calcium, magnesium, potassium, sodium, and selenium were below the Institute of Medicine Adequate Intake for both sexes at all 3 stages of lactation. In early lactation, multiple linear regressions showed that PC1 (calcium, magnesium, potassium, rubidium, and strontium intakes) was positively associated with WAZ, LAZ, and HCAZ. In established lactation, the same PC with sodium added was positively associated with all 3 anthropometric outcomes; a second PC (PC2: zinc, copper, and selenium intakes) was associated with WAZ and LAZ but not HCAZ. CONCLUSIONS: Breast milk may be inadequate in selected minerals and trace elements where higher estimated intakes were associated with greater infant growth. PMID- 27558579 TI - Processed Meat, but Not Unprocessed Red Meat, Is Inversely Associated with Leukocyte Telomere Length in the Strong Heart Family Study. AB - BACKGROUND: Telomeres are repetitive nucleotide sequences (TTAGGG) and their associated proteins at the end of eukaryote chromosomes. Telomere length shortens throughout the lifespan with each cell division, and leukocyte telomere length (LTL) is often used as a biomarker of cellular aging. LTL is related to many chronic diseases, including cardiovascular disease and diabetes. However, to our knowledge, the relation between LTL and risk factors for cardiovascular disease and diabetes, such as dietary intake of processed meat and unprocessed red meat, is largely unknown. OBJECTIVE: We examined the associations of processed meat intake and unprocessed red meat intake with LTL. METHODS: This cross-sectional study comprised 2846 American Indians from the Strong Heart Family Study who participated in the 2001-2003 examination. Dietary factors, including past-year consumption of processed meat and unprocessed red meat, were assessed with the use of a 119-item Block Food-Frequency Questionnaire. LTL was measured with the use of quantitative polymerase chain reaction. Generalized estimating equations were used to examine the associations of intake of processed meat and unprocessed red meat with LTL. RESULTS: Consumption of processed meat was negatively associated with LTL after adjustment for age, sex, site, education, smoking, alcohol use, physical activity, and other dietary factors. For every additional daily serving of processed meat, LTL was 0.021 units (telomeric product-to-single copy gene ratio) shorter (beta +/- SE = -0.021 +/- 0.008, P = 0.009). No association was observed between the intake of unprocessed red meat and LTL (beta +/- SE = 0.008 +/- 0.011, P = 0.46). CONCLUSIONS: In the Strong Heart Family Study, consumption of processed meat, but not unprocessed red meat, was associated with shorter LTL, a potential mediator for several age-related diseases. Further studies are needed to better understand the biological mechanism by which processed meat intake influences cellular aging. PMID- 27558580 TI - Large Portions Encourage the Selection of Palatable Rather Than Filling Foods. AB - BACKGROUND: Portion size is an important driver of larger meals. However, effects on food choice remain unclear. OBJECTIVE: Our aim was to identify how portion size influences the effect of palatability and expected satiety on choice. METHODS: In Study 1, adult participants (n = 24, 87.5% women) evaluated the palatability and expected satiety of 5 lunchtime meals and ranked them in order of preference. Separate ranks were elicited for equicaloric portions from 100 to 800 kcal (100-kcal steps). In Study 2, adult participants (n = 24, 75% women) evaluated 9 meals and ranked 100-600 kcal portions in 3 contexts (scenarios), believing that 1) the next meal would be at 1900, 2) they would receive only a bite of one food, and 3) a favorite dish would be offered immediately afterwards. Regression analysis was used to quantify predictors of choice. RESULTS: In Study 1, the extent to which expected satiety and palatability predicted choice was highly dependent on portion size (P < 0.001). With smaller portions, expected satiety was a positive predictor, playing a role equal to palatability (100-kcal portions: expected satiety, beta: 0.42; palatability, beta: 0.46). With larger portions, palatability was a strong predictor (600-kcal portions: beta: 0.53), and expected satiety was a poor or negative predictor (600-kcal portions: beta: 0.42). In Study 2, this pattern was moderated by context (P = 0.024). Results from scenario 1 replicated Study 1. However, expected satiety was a poor predictor in both scenario 2 (expected satiety was irrelevant) and scenario 3 (satiety was guaranteed), and palatability was the primary driver of choice across all portions. CONCLUSIONS: In adults, expected satiety influences food choice, but only when small equicaloric portions are compared. Larger portions not only promote the consumption of larger meals, but they encourage the adoption of food choice strategies motivated solely by palatability. PMID- 27558581 TI - Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention. AB - The percentage of elderly people with associated age-related health deterioration, including cancer, has been increasing for decades. Among age related diseases, the incidence of cancer has grown substantially, in part because of the overlap of some molecular pathways between cancer and aging. Studies with model organisms suggest that aging and age-related conditions are manipulable processes that can be modified by both genetic and environmental factors, including dietary habits. Variations in genetic backgrounds likely lead to differential responses to dietary changes and account for some of the inconsistencies found in the literature. The intricacies of the aging process, coupled with the interrelational role of bioactive food components on gene expression, make this review a complex undertaking. Nevertheless, intriguing evidence suggests that dietary habits can manipulate the aging process and/or its consequences and potentially may have unprecedented health benefits. The present review focuses on 4 cellular events: telomerase activity, bioenergetics, DNA repair, and oxidative stress. These processes are linked to both aging and cancer risk, and their alteration in animal models by selected food components is evident. PMID- 27558582 TI - Multidrug resistant Pseudomonas aeruginosa survey in a stream receiving effluents from ineffective wastewater hospital plants. AB - BACKGROUND: Multi-drug resistant forms of Pseudomonas aeruginosa (MDRPA) are a major source of nosocomial infections and when discharged into streams and rivers from hospital wastewater treatment plants (HWWTP) they are known to be able to persist for extended periods. In the city of Manaus (Western Brazilian Amazon), the effluent of three HWWTPs feed into the urban Mindu stream which crosses the city from its rainforest source before draining into the Rio Negro. The stream is routinely used by Manaus residents for bathing and cleaning (of clothes as well as domestic utensils) and, during periods of flooding, can contaminate wells used for drinking water. RESULTS: 16S rRNA metagenomic sequence analysis of 293 cloned PCR fragments, detected an abundance of Pseudomonas aeruginosa (P. aeruginosa) at the stream's Rio Negro drainage site, but failed to detect it at the stream's source. An array of antimicrobial resistance profiles and resistance to all 14 tested antimicrobials was detected among P. aeruginosa cultures prepared from wastewater samples taken from water entering and being discharged from a Manaus HWWTP. Just one P. aeruginosa antimicrobial resistance profile, however, was detected from cultures made from Mindu stream isolates. Comparisons made between P. aeruginosa isolates' genomic DNA restriction enzyme digest fingerprints, failed to determine if any of the P. aeruginosa found in the Mindu stream were of HWWTP origin, but suggested that Mindu stream P. aeruginosa are from diverse origins. Culturing experiments also showed that P. aeruginosa biofilm formation and the extent of biofilm formation produced were both significantly higher in multi drug resistant forms of P. aeruginosa. CONCLUSIONS: Our results show that a diverse range of MDRPA are being discharged in an urban stream from a HWWTP in Manaus and that P. aeruginosa strains with ampicillin and amikacin can persist well within it. PMID- 27558583 TI - Ultrasonographic evaluation of joint damage in knee osteoarthritis: feature specific comparisons with conventional radiography. AB - OBJECTIVE: The main aim of this study was to compare ultrasonography (US) with conventional radiography for the assessment of joint damage in knee OA. METHODS: A total of 166 knees of 84 patients (59 women and 25 men) with primary knee OA were included in this study. The femoral hyaline cartilage of the medial para patellar aspect and the osteophytes of both the medial and lateral femoral condyle were assessed. The cartilage and osteophytes were both quantitatively and qualitatively assessed. The US assessment was feature-specifically compared with conventional radiography. RESULTS: There was a strong correlation between the radiographic medial tibiofemoral narrowing grade and the US medial cartilage grade (rs = 0.7144, 95% CI: 0.6218, 0.7873, P < 0.0001). In the detailed analysis, US could assess cartilage damage more correctly by using the direct visualization technique. A strong correlation was also found between the radiographic and the US medial femoral osteophyte grade (rs = 0.7515, 95% CI: 0.6659, 0.8176, P < 0.0001) and between the radiographic and the US lateral femoral osteophyte grade (rs = 0.6947, 95% CI: 0.5941, 0.7739, P < 0.0001). US detected osteophytes in 46 sites at which conventional radiography did not detect any osteophytes. CONCLUSION: The present feature-specific comparison study provides evidence supporting the concurrent validity of US in the assessment of knee joint damage due to OA through its agreement with conventional radiography. Moreover, US was found to be a sensitive imaging technique for revealing cartilage damage and even minimal osteophytes, especially in the early radiographic stages of knee OA. PMID- 27558584 TI - BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics. PMID- 27558586 TI - Allergen-specific immunotherapy: is it vaccination against toxins after all? AB - IgE-mediated allergies, in particular allergic rhinoconjunctivitis and asthma, have reached epidemic proportions, affecting about one-third of the population in developed countries. The most effective treatment for allergies is specific immunotherapy (SIT), which involves the injection of increasing doses of an allergen extract to allergic individuals. The current form of SIT was first introduced in 1911 and recently celebrated its 100th birthday for the treatment of hay fever. The concept of this therapy at the time was straightforward, as it was believed that pollen contained toxins against which the patient could be vaccinated. However, the understanding became blurred with the discovery that IgE antibodies were the effector molecules of the allergic response. Subsequent research focused on the idea that SIT should induce tolerance keeping the IgE antibodies at bay. In this review, we will discuss the various hypotheses for the mechanism of SIT and we will put forward the concept that allergens may be viewed as 'protoxins' which need to be activated by IgE antibodies. Within this framework, protoxin-neutralizing antibodies are the key effector molecules while a shift to Th1 or Treg cells mainly contributes to the efficacy of SIT by helping B cells to produce neutralizing IgG antibodies. PMID- 27558585 TI - Efficacy and tolerability of Meratrim for weight management: a randomized, double blind, placebo-controlled study in healthy overweight human subjects. AB - BACKGROUND: Meratrim is a blend of two plant extracts obtained from Sphaeranthus indicus flower heads and Garcinia mangostana fruit rinds. Previous studies have demonstrated that Meratrim is effective for weight management in obese individuals. The objective of this study was to assess the efficacy and tolerability of Meratrim in managing body weight in healthy overweight subjects. METHODS: Sixty participants with a mean BMI of 28.3 kg/m(2) were randomized into two groups receiving either 400 mg of Meratrim twice daily or two identical placebo capsules for a period of 16 weeks. Subjects were asked to consume about 2,000 kcal/day throughout the study period and walk 5 days a week for 30 min daily. The primary endpoint was defined as the change in body weight from baseline to end of week 16 for the Meratrim group versus placebo. Fifty seven subjects completed the trial. RESULTS: At study conclusion, statistically significant reductions in body weight (5.09 vs. 1.1 kg; p < 0.0001), BMI (1.91 vs. 0.43 kg/m(2); p < 0.0001), waist (9.97 vs. 3.71 cm; p < 0.001) and hip size (10.38 vs. 5.11 cm; p < 0.0001) were observed in the Meratrim versus the placebo group. Additionally, a significant change in serum LDL (-14.79 vs. 6.25 mg/dL; p < 0.0001), triglycerides (-43.62 vs. -13.68 mg/dL; p < 0.001) and total cholesterol (-20.0 vs. -0.75 mg/dL; p = 0.0002) was observed in the Meratrim cohort compared to the placebo. No supplementation related adverse events were noted during the study. CONCLUSIONS: The study findings suggest that Meratrim is well-tolerated and is an effective ingredient for weight management in healthy overweight subjects. TRIAL REGISTRATION: CTRI/2014/07/004727; www.CTRI.nic.in. PMID- 27558587 TI - Kamishoyosan reduces conditioned fear-induced freezing behavior in socially isolated ovariectomized rats. AB - In the present study, we investigated the effect of kamishoyosan (KSS) on conditioned fear-induced freezing in ovariectomized (OVX) rats. Socially isolated OVX rats showed the longest freezing time among the following four groups: group housed sham-operated (Sham), isolated Sham, group-housed OVX, and isolated OVX rats. Repeated oral administration of KSS (30-300 mg/kg) reduced conditioned fear induced freezing in socially isolated OVX rats. The reduction of freezing by KSS was reversed by flumazenil (3 mg/kg) and bicuculline (3 mg/kg). These findings suggest that the GABAA-benzodiazepine receptor complex is involved in the anxiolytic effect of KSS in socially isolated OVX rats. PMID- 27558588 TI - An Evaluation Method for the Suppression of Pathogenic Fusarium oxysporum by Soil Microorganisms Using the Dilution Plate Technique. AB - Soil-borne diseases caused by pathogenic microorganisms are one of the main factors responsible for the decline in crop yields in farmlands. Pathogenic Fusarium oxysporum causes serious damage to various crops, and, thus, a feasible diagnostic method for soil-borne diseases is required. We herein examined a simple method to evaluate the suppressiveness of soil microorganisms against a pathogen by co-cultivating indigenous soil microorganisms and a pathogenic fungus (F. oxysporum f. sp. spinaciae). We inoculated F. oxysporum onto the center of agar medium plates mixed with a dilution series of a suspension of organic fertilizers or soil. After an approximately one-week cultivation, the growth degree of F. oxysporum was estimated based on the size of the colonies that formed on the plates. The growth degree of F. oxysporum significantly differed among the organic fertilizers tested, indicating the usefulness of the method for evaluating suppressiveness by organic fertilizers. Differences in the growth degrees of F. oxysporum were associated with the incidence of disease in spinach on soil treated with organic fertilizers and inoculated with a pathogenic F. oxysporum strain. These results suggested that this method provides some useful information on the suppressiveness of organic fertilizers and soil against Fusarium wilt. PMID- 27558589 TI - The effect of clinical features and glucocorticoids on biopsy findings in giant cell arteritis. AB - BACKGROUND: To investigate the effect of baseline clinical characteristics and glucocorticoid treatment on temporal artery biopsy (TAB) findings in patients with giant cell arteritis (GCA). METHODS: Individuals who developed GCA after inclusion in two population-based health surveys were identified through linkage to the local and the national patient registers. In addition, other patients diagnosed with GCA at the Departments of Internal Medicine and Rheumatology at an area hospital were included. A structured review of medical records and TAB pathology reports was performed. The presence or absence of giant cells, granuloma, fragmented internal elastic lamina, fibrosis and grade of inflammatory infiltrates were recorded. RESULTS: In 183 cases with a confirmed clinical diagnosis of GCA, 139 were biopsied after start of glucocorticoids (median treatment duration 3 days; interquartile range 2-5). Patients with a positive TAB (77 %) had significantly higher C-reactive protein (CRP; p = 0.007) and erythrocyte sedimentation rate (ESR; p = 0.03) at the time of clinical diagnosis. A positive TAB tended to more common in women, but there was no difference in the proportion of patients with polymyalgia rheumatica or visual symptoms. Patients biopsied before or on the same day as initial treatment where more likely than those biopsied 1-3 days after treatment start to have positive biopsy [odds ratio (OR) 2.86; 95 % CI 1.06-7.70] as well as inflammatory infiltrates (OR 3.30; 95 % CI 1.15-9.49). There was no significant difference in the proportions of a fragmented internal lamina (p = 0.86), giant cells (p = 0.10), granuloma (p = 0.19), minor inflammatory infiltrates (p = 0.47), major inflammatory infiltrates (p = 0.09), or overall positive biopsy (p = 0.17) report by treatment duration comparing: <= 0 days, 1-3 days, 4-6 days, 7-28 days. Among those biopsied 7-28 days after start of treatment, 80 % of TABs were positive, and histopathology features were not substantially different from those biopsied after shorter glucocorticoid treatment. CONCLUSION: Biopsies were more likely to be positive and have characteristic histopathologic features in patients with high CRP and ESR, and prior to start of corticosteroid treatment TABs taken 1-4 weeks after initiation of glucocorticoid treatment reveal changes consistent with GCA and therefore still yields clinically useful information for the diagnosis. PMID- 27558591 TI - Prohibitin involvement in the generation of mitochondrial superoxide at complex I in human sperm. AB - Prohibitin (PHB), a major mitochondrial membrane protein, has been shown earlier in our laboratoryto regulate sperm motility via an alteration in mitochondrial membrane potential (MMP) in infertile men with poor sperm quality. To test if PHB expression is associated with sperm mitochondrial superoxide (mROS) levels, here we examined sperm mROS levels, high MMP and lipid peroxidation in infertile men with poor sperm motility (asthenospermia, A) and/or low sperm concentrations (oligoasthenospermia, OA). The diaphorase-type activity of sperm mitochondrial complex I (MCI) and PHB expression were also determined. We demonstrate that mROS and lipid peroxidation levels are significantly higher in sperm from A and OA subjects than in normospermic subjects, whereas high MMP and PHB expression are significantly lower. A positive correlation between mROS and lipid peroxidation and a negative correlation of mROS with PHB expression, high MMP, and sperm motility were found in these subjects. The finding of similar diaphorase-type activity levels of sperm MCI in the three groups studied suggests that the catalytic subunits of MCI in the matrix arm may produce mROS on its own. There may be a dysfunction of electron transport at MCI associated with decreased expression of PHB in sperm with poor quality. We conclude that mROS level is increased and associated with decreased PHB expression, and it may regulate sperm motility via increases in low MMP and lipid peroxidation. This is the first report on the involvement of PHB in human sperm motility loss associated with increased generation of mROS at MCI. PMID- 27558592 TI - Antioxidative and antibacterial peptides derived from bovine milk proteins. AB - The search for alternative preservatives is on the rise due to safety issues linked with the application of synthetic antioxidants and the extensive increase in bacterial resistance to several conventional antibiotics. Therefore, the quest for finding suitable alternatives including bioactive peptides has received attention. This article reports a comprehensive insight concerning antioxidative and antibacterial peptides derived from milk proteins, a prolific source of peptides having various bioactivities. Caseins and whey proteins have also been evaluated for antioxidative and antibacterial potential using the BIOPEP database. A notable number of potentially active peptides are present in milk proteins. Technological approaches are here reported for the production of these peptides. The findings of this review show potentiality of utilizing dairy derived antioxidative and antibacterial peptides in the development of a superior alternative to the current generation of preservatives and therapeutic agents, as well as a functional ingredient in dietetic or pharmaceutical applications. PMID- 27558590 TI - Opposing regulation of the late phase TNF response by mTORC1-IL-10 signaling and hypoxia in human macrophages. AB - Tumor necrosis factor (TNF) is best known for inducing a rapid but transient NF kappaB-mediated inflammatory response. We investigated later phases of TNF signaling, after the initial transient induction of inflammatory genes has subsided, in primary human macrophages. TNF signaling induced expression of late response genes, including inhibitors of NF-kappaB and TLR signaling, with delayed and sustained kinetics 6-24 hr after TNF stimulation. A subset of late phase genes was expressed in rheumatoid arthritis synovial macrophages, confirming their expression under chronic inflammatory conditions in vivo. Expression of a subset of late phase genes was mediated by autocrine IL-10, which activated STAT3 with delayed kinetics. Hypoxia, which occurs at sites of infection or inflammation where TNF is expressed, suppressed this IL-10-STAT3 autocrine loop and expression of late phase genes. TNF-induced expression of IL-10 and downstream genes was also dependent on signaling by mTORC1, which senses the metabolic state of cells and is modulated by hypoxia. These results reveal an mTORC1-dependent IL-10-mediated late phase response to TNF by primary human macrophages, and identify suppression of IL-10 responses as a new mechanism by which hypoxia can promote inflammation. Thus, hypoxic and metabolic pathways may modulate TNF responses during chronic inflammation. PMID- 27558593 TI - Associated factors and persistence of palatal groove in preterm infants: a cohort study. AB - BACKGROUND: There is a lack of evidence on the relationship between prematurity and palatal abnormalities. The aim of this study was to evaluate the incidence of palatal groove, the associated factors and the persistence time in preterm infants from birth to 24 months of age. METHODS: The children's data, medical history and eating habits were collected using a questionnaire answered by the legal guardian and updated every dental visit. Natal and neonatal data were obtained from the medical records. During the orofacial examination, the presence or absence of a palatal groove was observed. In order to evaluate for associations between independent variables and the palatal groove, descriptive analyses and bivariate analyses were conducted using the Mann-Whitney, Pearson's chi-squared and Fisher's exact tests, when appropriate. The Poisson regression analysis was used to determine risk and protective factors for the occurrence of palatal groove. The significance level was 0.05. For the persistence of palatal groove, a survival analysis was used (Kaplan Meier method). RESULTS: Seventy-four preterm infants were monitored. Palatal groove occurred in n = 19 (25.7 %) and persisted for an average time of 12 months. Bivariate analysis showed a significantly higher occurrence of palatal groove in girls (68.4 % vs 40 % with non-occurrence of palatal groove) as well as in infants that stayed longer in the neonatal intensive care unit (NICU) (median 37 days vs 20 days), that did not have exclusive breastfeeding (94.7 % vs 69.1 %), were intubated (median five days vs one day) or used an orogastric tube (median 33 days vs 15 days). The quantitative data for 'NICU', 'intubation' and 'orogastric tube' were correlated and estimated as risk factors for palatal groove formation in the unadjusted Poisson regression analysis. CONCLUSIONS: Palatal groove occur transiently in approximately one quarter of preterm infants, especially in infants that stay longer in the NICU, are intubated or use an orogastric tube. PMID- 27558594 TI - A kiss to set the rhythm. AB - Groups of neurons in the hypothalamus synchronize their activity to trigger the production of hormones that sustain fertility. PMID- 27558595 TI - A set of Triticum aestivum-Aegilops speltoides Robertsonian translocation lines. AB - KEY MESSAGE: Here we report the production of a set of wheat - Aegilops speltoides Robertsonian translocations covering all Ae. speltoides chromosome arms except the long arm of the homoeologous group 4 chromosome. Aegilops speltoides of the Poaceae family is the most probable donor of the B and G genomes of polyploid Triticum species and also an important source of resistance to diseases and pests of wheat. Previously, we reported the production of a complete set of T aestivum-Ae. speltoides chromosome addition lines and a set of disomic S(B/A)-genome chromosome substitution lines. The isolation of compensating Robertsonian translocations (RobTs) composed of alien chromosome arms translocated to homoeologous wheat chromosome arms is the important next step to exploit the genetic variation of a wild relative of wheat. Here, we report the development of molecular markers specific for the S-genome chromosomes and their use in the isolation of a set of 13 compensating wheat-Ae. speltoides RobTs covering the S genome of Ae. speltoides except for the long arm of chromosome 4S. Most of the RobTs were fully fertile and will facilitate mapping of genes to specific chromosome arms and also will accelerate the introgression of agronomically useful traits from Ae. speltoides into wheat by homologous recombination. PMID- 27558596 TI - Derivation of the clinical grade human embryonic stem cell line RCe021-A (RC-17). AB - The human embryonic stem cell line RCe021-A (RC-17) was derived under quality assured compliance with UK regulation, European Union Directives and International guidance for tissue procurement, processing and storage according to Good Manufacturing Practice (GMP) standards. The cell line was derived from a day 3 embryo voluntarily donated as unsuitable or surplus to fertility requirements following informed consent. RCe021-A (RC-17) shows normal pluripotency marker expression and differentiation to the three germ layers in vitro. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data are available. PMID- 27558597 TI - Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC2. AB - Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC2, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC2 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs. PMID- 27558598 TI - Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC4. AB - Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC4, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC4 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs. PMID- 27558599 TI - Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC1. AB - Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC1, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layers. WT-iPSC1 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs. PMID- 27558600 TI - Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a patient with recessive dystrophic epidermolysis bullosa (RDEB) carrying two compound heterozygous mutations in the COL7A1 gene. AB - Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, RDEB-iPSC26, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. RDEB-iPSC26 may be a useful cell resource for the establishment of in vitro RDEB modeling and the study for developing gene and cell therapy. PMID- 27558601 TI - Derivation of the clinical grade human embryonic stem cell line RCe013-A (RC-9). AB - The human embryonic stem cell line RCe013-A (RC-9) was derived under quality assured compliance with UK regulation, European Union Directives and International guidance for tissue procurement, processing and storage according to Good Manufacturing Practice (GMP) standards. The cell line was derived from a failed to fertilise oocyte voluntarily donated as unsuitable and surplus to fertility requirements following informed consent. RCe013-A (RC-9) shows normal pluripotency marker expression and differentiation to the three germ layers in vitro and in vivo. It has a normal 46XY male karyotype and microsatellite PCR identity, HLA and blood group typing data are available. PMID- 27558602 TI - Derivation of the clinical grade human embryonic stem cell line RCe015-A (RC-11). AB - The human embryonic stem cell line RCe015-A (RC-11) was derived under quality assured compliance with UK regulation, European Union Directives and International guidance for tissue procurement, processing and storage according to Good Manufacturing Practice (GMP) standards. The cell line was derived from a fragmented cleavage stage embryo voluntarily donated as unsuitable or surplus to fertility requirements following informed consent. RCe015-A (RC-11) shows normal pluripotency marker expression and differentiation to the three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data are available. PMID- 27558603 TI - An improved reprogrammable mouse model harbouring the reverse tetracycline controlled transcriptional transactivator 3. AB - Reprogrammable mouse models engineered to conditionally express Oct-4, Klf-4, Sox 2 and c-Myc (OKSM) have been instrumental in dissecting molecular events underpinning the generation of induced pluripotent stem cells. However, until now these models have been reported in the context of the m2 reverse tetracycline controlled transactivator, which results in low reprogramming efficiency and consequently limits the number of reprogramming intermediates that can be isolated for downstream profiling. Here, we describe an improved OKSM mouse model in the context of the reverse tetracycline-controlled transactivator 3 with enhanced reprogramming efficiency (>9-fold) and increased numbers of reprogramming intermediate cells albeit with similar kinetics, which we believe will facilitate mechanistic studies of the reprogramming process. PMID- 27558605 TI - Establishment of induced pluripotent stem cell (iPSC) line from a 57-year old patient with sporadic Alzheimer's disease. AB - Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 57-year old woman with sporadic Alzheimer's disease. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies. PMID- 27558604 TI - Establishment of PSEN1 mutant induced pluripotent stem cell (iPSC) line from an Alzheimer's disease (AD) female patient. PMID- 27558606 TI - Establishment of induced pluripotent stem cell (iPSC) line from an 84-year old patient with late onset Alzheimer's disease (LOAD). AB - Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 84-year old male with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies. PMID- 27558607 TI - Establishment of induced pluripotent stem cell (iPSC) line from a 63-year old patient with late onset Alzheimer's disease (LOAD). AB - Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 63-year old woman with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies. PMID- 27558608 TI - Establishment of induced pluripotent stem cell (iPSC) line from a 75-year old patient with late onset Alzheimer's disease (LOAD). AB - Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 75-year old woman with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies. PMID- 27558609 TI - A human MIXL1 green fluorescent protein reporter embryonic stem cell line engineered using TALEN-based genome editing. AB - We have generated a MIXL1-eGFP reporter human embryonic stem cell (hESC) line using TALEN-based genome engineering. This line accurately traces endogenous MIXL1 expression via an eGFP reporter to mesendodermal precursor cells. The utility of the MIXL1-eGFP reporter hESC line lies in the prospective isolation, lineage tracing, and developmental and mechanistic studies of MIXL1+ cell populations. PMID- 27558610 TI - Generation of iPS cell lines from schizophrenia patients using a non-integrative method. PMID- 27558611 TI - Generation of urine iPS cell lines from patients with Attention Deficit Hyperactivity Disorder (ADHD) using a non-integrative method. AB - Urine samples were collected from three patients (2 males, 1 female) with clinically diagnosed Attention Deficit Hyperactivity Disorder (ADHD) according to DSM-5 criteria using semi-structured interviews (K-SADS adapted for adults) by a trained psychiatrist. Urine epithelial cell lines were established and expanded for subsequent reprogramming procedure. Induced pluripotent stem cells (iPSCs) were derived using integration-free CytoTune(r)-iPS 2.0 Sendai Reprogramming Kit, which includes Sendai virus particles of the four Yamanaka factors Oct3/4, Sox2, Klf4 and c-Myc. PMID- 27558612 TI - Generation of urine iPS cell line from a patient with obsessive-compulsive disorder using a non-integrative method. PMID- 27558613 TI - Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific heterozygous mutation in CHMP2B. AB - Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). We have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into one of the alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3. PMID- 27558614 TI - Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific homozygous mutation in CHMP2B. AB - Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). We have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into both alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B dependent phenotypes of FTD3. PMID- 27558615 TI - Generation of an induced pluripotent stem cell line from a patient with hereditary multiple endocrine neoplasia 2A (MEN2A) syndrome with RET mutation. AB - Multiple Endocrine Neoplasia Type 2A (MEN2A) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC), pheochromocytoma, hyperparathyroidism and cutaneous lichen amyloidosis (CLA) and/or Hirschsprung disease in some variants. Currently, there is no satisfactory animal model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 634 who developed pheochromocytoma and MTC. RETC634Y mutated cells were reprogrammed by non-integrative viral transduction. These iPSCs had normal karyotype, harboured the RETC634Y mutation and expressed pluripotency hallmarks as well as RET. A comprehensive pathological assessment of teratoma was performed after injection in immunodeficient mice. PMID- 27558616 TI - Generation of human iPS cell line SKiPSc1 from healthy Human Neonatal Foreskin Fibroblast cells. AB - The SKiPSc1 induced pluripotent stem (iPS) cell line was generated from Human Neonatal Foreskin Fibroblasts (HNFFs) obtained from a healthy donor infant that were reprogrammed using non-integrating Sendai viral vectors expressing Oct3/4, Sox2, c-Myc, and Klf4. PMID- 27558617 TI - A modified single-cell electroporation method for molecule delivery into a motile protist, Euglena gracilis. AB - Single-cell transfection is a powerful technique for delivering chemicals, drugs, or probes into arbitrary, specific single cells. This technique is especially important when the analysis of molecular function and cellular behavior in individual microscopic organisms such as protists requires the precise identification of the target cell, as fluorescence labeling of bulk populations makes tracking of individual motile protists virtually impossible. Herein, we have modified current single-cell electroporation techniques for delivering fluorescent markers into single Euglena gracilis, a motile photosynthetic microalga. Single-cell electroporation introduced molecules into individual living E. gracilis cells after a negative pressure was applied through a syringe connected to the micropipette to the target cell. The new method achieves high transfection efficiency and viability after electroporation. With the new technique, we successfully introduced a variety of molecules such as GFP, Alexa Fluor 488, and exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) RNA probes into individual motile E. gracilis cells. We demonstrate imaging of endogenous mRNA in living E. gracilis without interfering with their physiological functions, such as swimming or division, over an extended period of time. Thus the modified single-cell electroporation technique is suitable for delivering versatile functional molecules into individual motile protists. PMID- 27558620 TI - The Clinical Dilemma of Calcium Supplementation After Bariatric Surgery: Calcium Citrate or Calcium Carbonate That Is the Question? PMID- 27558618 TI - Optimal turnaround time for direct identification of microorganisms by mass spectrometry in blood culture. AB - INTRODUCTION: During the past few years, several studies describing direct identification of bacteria from blood culture using mass spectrometry have been published. These methods cannot, however, be easily integrated into a common laboratory workflow because of the high hands-on time they require. In this paper, we propose a new method of identification with a short hands-on time and a turnaround time shorter than 15min. MATERIALS AND METHODS: Positive blood bottles were homogenised and 600MUL of blood were transferred to an Eppendorf tube where 600MUL of lysis buffer were added. After homogenisation, a centrifugation step of 4min at 10,500g was performed and the supernatant was discarded. The pellet was then washed and loaded in quadruplicate into wells of a Vitek(r) MS-DS plate. Each well was covered with a saturated matrix solution and a MALDI-TOF mass spectrometry analysis was performed. Species were identified using the software Myla 3.2.0-2. RESULTS: We analysed 266 positive blood culture bottles. A microorganism grew in 261 cultures, while five bottles remained sterile after 48h of incubation in subculture. Our method reaches a probability of detection at the species level of 77.8% (203/261) with a positive predictive value of 99.5% (202/203). CONCLUSION: We developed a new method for the identification of microorganisms using mass spectrometry, directly performed from a positive blood culture. This method has short hands-on time and turnaround time and can easily take place in the workflow of a laboratory, with comparable results in performance with other methods reported in the literature. PMID- 27558619 TI - Cross-species prediction of human survival probabilities for accelerated anthrax vaccine absorbed (AVA) regimens and the potential for vaccine and antibiotic dose sparing. AB - Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure. A nonhuman primate (NHP) study was completed to evaluate the efficacy of a two dose anthrax vaccine absorbed (AVA) schedule (0, 2weeks) aerosol challenged with high levels of B. anthracis spores at week4- the time point at which humans would receive the third vaccination of the approved PEP schedule. Here we use logistic regression models to combine the survival data from the NHP study along with serum anthrax lethal toxin neutralizing activity (TNA) and anti-PA IgG measured by enzyme linked immunosorbent assay (ELISA) data to perform a cross-species analysis to estimate survival probabilities in vaccinated human populations at this time interval (week4 of the PEP schedule). The bridging analysis demonstrated that high levels of NHP protection also yield high predicted probability of human survival just 2weeks after the second dose of vaccine with the full or half antigen dose regimen. The absolute difference in probability of human survival between the full and half antigen dose was estimated to be at most approximately 20%, indicating that more investigation of the half-antigen dose for vaccine dose sparing strategies may be warranted. PMID- 27558621 TI - Does Certification as Bariatric Surgery Center and Volume Influence the Outcome in RYGB-Data Analysis of German Bariatric Surgery Registry. AB - AIM: To examine the association between the certification as bariatric surgery center and volume and patient outcome, data collected in the German Bariatric Surgery Registry were evaluated. All data were registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at Otto-von Guericke University Magdeburg. METHODS: Data collection began in 2005 for all bariatric procedures in an online database. Participation in the quality assurance study is required for all certified bariatric surgery centers in Germany. Descriptive evaluation and matched pairs analysis were performed. Patients were matched via propensity score taking into account BMI, age, and incidence of comorbidities. RESULTS: During the period from 2005 to 2013, 3083 male and 10,639 female patients were operated on with the RYGB primary approach. In Centers of Competence (77.2 %) and non-accredited hospitals (76.3 %), the proportion of female patients was significantly lower than in Centers of Reference/Excellence (78.7 %; p = 0.002). The mean age in Centers of Reference/Excellence (41.2 years) was significantly lower than in Centers of Competence (43.2 years; p < 0.05). Propensity score analysis was performed to compare matched patients with regard to BMI, age, and incidence of comorbidities. The rate of general and surgical postoperative complications and mortality rate was significantly lower in certified Centers of Reference/Excellence compared to Centers of Competence with 29 and non-certified hospitals. CONCLUSION: There is evidence of improved patient outcome in certified bariatric surgery centers with higher volume. The study supports the concept of certification. There are different factors which can and cannot be preoperatively modified and influence the perioperative outcome. PMID- 27558622 TI - Physiotherapists' perceptions of patient adherence to prescribed self-management strategies: a cross-sectional survey of Australian physiotherapists. AB - PURPOSE: Physiotherapists often prescribe self-management strategies for their patients. However, the effectiveness of these strategies in improving patient outcome is related to the rate of patient adherence. The aims of this study were to explore physiotherapists' views on the importance and perceived rates of patient adherence to physiotherapist prescribed self-management strategies; the perceived importance of methods physiotherapists can employ to aid patient adherence and the barriers to employing these methods. METHOD: A cross-sectional web-based survey was emailed to 808 physiotherapist members of the Australian Physiotherapy Association. To maximize response rates, two reminder emails were utilized. RESULTS: In total, 352 physiotherapists completed the survey (response rate 44%). A majority of physiotherapists (89%) believed that patient self management strategies were important in improving patient outcomes; however, the mean perceived rate of patient adherence across all strategies was only 67%. Physiotherapists reported that there were a number of important methods that can be employed to aid patient adherence such as providing patient education and allowing time for patient practice; with minimal perceived barriers to employing these methods. CONCLUSIONS: Results indicate that physiotherapists perceive that patient outcomes can be positively impacted by patient adherence to a range of self-management strategies. Physiotherapists should be encouraged to implement into their routine clinical practice evidence-based methods to aid patient adherence. Implications for Rehabilitation Physiotherapists believe that patient self-management strategies are important for improving patient outcomes, however, the perceived rates of patient adherence could be improved. Physiotherapists should adopt a collaborative approach with their patients to address any barriers to adherence to positively impact on patient outcome. Physiotherapists perceive that there are a number of modifiable characteristics which determine patient adherence including patient self-efficacy, physiotherapist communication skills and the complexity of the self-management strategy. Methods that physiotherapists can employ to positively influence patient adherence may include individualizing the strategy to the patient, education and supplementary written information. PMID- 27558623 TI - Government's own documents question "seven day NHS" feasibility. PMID- 27558624 TI - Towards interpretation of intermolecular paramagnetic relaxation enhancement outside the fast exchange limit. AB - In an exchanging system between major and minor species, the transverse paramagnetic relaxation enhancement rate observed on the resonances of the major species (Gamma 2 (app) ) is dependent upon the exchange regime between the species. Quantitative analysis of PRE data in such systems typically assumes that the overall exchange rate k ex between the species is fast on the PRE time scale (k ex ? Gamma2). Recently, we have characterized the kinetics of binding of the model protein ubiquitin to large (LUV) and small (SUV) unilamellar lipid-based nanoparticles or liposomes (Ceccon A, Tugarinov V, Bax A, Clore GM (2016). J Am Chem Soc 138:5789-5792). Building upon these results and taking advantage of a strong paramagnetic agent with an isotropic g-tensor, Gd(3+), we were able to measure intermolecular methyl carbon and proton PREs between paramagnetically tagged liposomes and ubiquitin. In the limit of fast exchange (k ex ? Gamma2) the ratio of the apparent proton to carbon methyl PREs, ((1)Hm-Gamma 2 (app) )/((13)Cm-Gamma 2 (app) ), is equal to the square of the ratio of the gyromagnetic ratios of the two nuclei, (gammaEta/gammaC)(2). However, outside the fast exchange regime, under intermediate exchange conditions (e.g. when Gamma2 is comparable in magnitude to k ex) the ((1)Hm-Gamma 2 (app) )/((13)Cm-Gamma 2 (app) ) ratio provides a reliable measure of the 'true' methyl PREs. PMID- 27558625 TI - St Gallen 2015 subtyping of luminal breast cancers: impact of different Ki67 based proliferation assessment methods. AB - Ki67 has been proposed as prognostic proliferation marker in luminal breast cancer (BC), but little is known on the influence of Ki67 assessment methods on subtyping into luminal A- and B-like tumors. Our aim was to study the influence of different Ki67-labeling index (Ki67-LI) assessment methods on the proportion of BCs classified as luminal A-like. 280 early BCs were subtyped according to the St Gallen 2015 definitions into 71 % luminal (HER2 negative), 6 % luminal B-like (HER2 positive), 13 % triple negative, 1 % HER2 positive (nonluminal), and 9 % special type. Digitized whole slides were counted manually on the screen. We used nine defined counting methods to assess the Ki67-LI (including the International Ki67 in Breast Cancer Working Group recommendations), and compared the resulting medians and the proportions of cancers classified as luminal A-like according to the formerly used cut-off <20 %. Methods assessing hot spots and tumor periphery resulted in significantly higher Ki67-LI medians than those measuring an average proliferation (27.45 % vs 16.96 %, p < 0.0001). Substantially lower median Ki67 LI were found when assessing 1020 compared to counting 100, 200, 300 cells (17.65 vs 33 %, vs 28 %, vs 24.33 %, respectively; p < 0.0001), or 510 cells (20.59 %, p = 0.019). Applying a standard Ki67-LI cut-off <20 % to define low proliferation for all methods, the proportion of luminal A-like cancers varied between 13 and 44 %. The proportion of BCs classified as luminal A-like is highly influenced by the Ki67-LI assessment method. As a consequence, the selection of a specific Ki67 LI assessment method may have a direct effect on the proportion of patients considered having low-risk disease and thus influence therapeutic decision making. This calls for a standardized assessment method. PMID- 27558626 TI - Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States. AB - Lyme borreliosis (LB) is a multisystem disease caused by spirochetes in the Borrelia burgdorferisensu lato (Bbsl) genospecies complex. We previously described a novel Bbsl genospecies (type strain MN14-1420T) that causes LB among patients with exposures to ticks in the upper midwestern USA. Patients infected with the novel Bbsl genospecies demonstrated higher levels of spirochetemia and somewhat differing clinical symptoms as compared with those infected with other Bbsl genospecies. The organism was detected from human specimens using PCR, microscopy, serology and culture. The taxonomic status was determined using an eight-housekeeping-gene (uvrA, rplB, recG, pyrG, pepX, clpX, clpA and nifS) multi locus sequence analysis (MLSA) and comparison of 16S rRNA gene, flaB, rrf-rrl, ospC and oppA2 nucleotide sequences. Using a system threshold of 98.3 % similarity for delineation of Bbsl genospecies by MLSA, we demonstrated that the novel species is a member of the Bbsl genospecies complex, most closely related to B. burgdorferisensu stricto (94.7-94.9 % similarity). This same species was identified in Ixodes scapularis ticks collected in Minnesota and Wisconsin. This novel species, Borrelia mayonii sp. nov, is formally described here. The type strain, MN14-1420, is available through the Deutsche Sammlung von Mikroorganismen und Zelkulturen GmbH (DSM 102811) and the American Type Culture Collection (ATCC BAA-2743). PMID- 27558628 TI - Another Step Forward: A Novel Approach to the Clinician-Educator Track for Residents. PMID- 27558627 TI - The neglect of treatment-construct validity in psychotherapy research: a systematic review of comparative RCTs of psychotherapy for Borderline Personality Disorder. AB - BACKGROUND: Randomized controlled trials (RCTs) are considered the best methodology for studying the efficacy of psychotherapy. Optimally an RCT design makes it possible to conclude that if one treatment has a better outcome than another, this is due to the treatment package (TP) as it was implemented in this particular context, rather than other factors beyond the treatment (= high internal validity). Strong internal validity does not, however, provide evidence for the treatment model (TM) that provides the theoretical basis of the TP, because the TP that is tested may differ from the comparison condition in a number of other ways that suggest alternative explanations for the effects. These alternative treatment contrasts represent threats to construct validity of the conclusions. Maximal construct validity requires (1) that the treatments are clearly contrasted on the experimental factors (treatment integrity), and (2) that alternative treatment contrasts can be eliminated. The analysis of alternative explanations is a neglected topic in psychotherapy research. To approach this problem, a methodology for the analysis of treatment contrasts is suggested and tested. METHODS: Two indexes were defined: (1) a Treatment Integrity Index (TII) and (2) an Alternative Treatment Contrast Index (ATCI). This methodological approach was applied to eight comparative RCTs of treatments for Borderline Personality Disorder (BPD), which were coded for a set of treatment contrasts independently by three coders. RESULTS: The analysis of the RCTs of treatments for BPD showed that construct validity differed widely between the different studies but was generally low (low TII and ATCI), and that it is therefore difficult to draw causal conclusions from this research. The publication policies of scientific journals in this area seldom require the systematic data relevant to an analysis of alternative explanations of the effects, which is needed to provide evidence for a particular TM. CONCLUSIONS: Research on psychotherapy needs to be refocused from treatment packages (TP) to treatment models (TM). This requires an improved conceptualization of the methodological principles and skills involved, and the development of valid measures of these, but also improved reporting standards concerning treatment construct validity in scientific journals. PMID- 27558629 TI - Using Video Recordings of Psychotherapy Sessions in Supervision: Strategies to Reduce Learner Anxiety. PMID- 27558630 TI - Cardiovascular risk outcome and program evaluation of a cluster randomised controlled trial of a community-based, lay peer led program for people with diabetes. AB - BACKGROUND: The 2013 Global Burden of Disease Study demonstrated the increasing burden of diabetes and the challenge it poses to the health systems of all countries. The chronic and complex nature of diabetes requires active self management by patients in addition to clinical management in order to achieve optimal glycaemic control and appropriate use of available clinical services. This study is an evaluation of a "real world" peer support program aimed at improving the control and management of type 2 diabetes (T2DM) in Australia. METHODS: The trial used a randomised cluster design with a peer support intervention and routine care control arms and 12-month follow up. Participants in both arms received a standardised session of self-management education at baseline. The intervention program comprised monthly community-based group meetings over 12 months led by trained peer supporters and active encouragement to use primary health care and other community resources and supports related to diabetes. Clinical, behavioural and other measures were collected at baseline, 6 and 12 months. The primary outcome was the predicted 5 year cardiovascular disease risk using the United Kingdom Prospective Diabetes Study (UKPDS) Risk Equation at 12 months. Secondary outcomes included clinical measures, quality of life, measures of support, psychosocial functioning and lifestyle measures. RESULTS: Eleven of 12 planned groups were successfully implemented in the intervention arm. Both the usual care and the intervention arms demonstrated a small reduction in 5 year UKPDS risk and the mean values for biochemical and anthropometric outcomes were close to target at 12 months. There were some small positive changes in self-management behaviours. CONCLUSIONS: The positive changes in self-management behaviours among intervention participants were not sufficient to reduce cardiovascular risk, possibly because approximately half of the study participants already had quite well controlled T2DM at baseline. Future research needs to address how to enhance community based programs so that they reach and benefit those most in need of resources and supports to improve metabolic control and associated clinical outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 . Registered 16 June 2009. PMID- 27558631 TI - A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study. AB - BACKGROUND: Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we investigated whether lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment. METHODS: Patients with RA who were receiving RTX for the first time were included in an observatory registry. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline and at week 24 after RTX. Complete data were available for 44 patients. Logistic regression and receiver operating characteristic curve analyses were computed to analyze the predictive value of lymphocyte subsets for European League Against Rheumatism (EULAR) response and LDA (defined as disease activity score in 28 joints (DAS28) <=3.2) at week 24. RESULTS: EULAR responders had lower total lymphocyte counts (LC), T cells and CD4 + T cells at baseline. Although these parameters were independent predictors of EULAR response they failed in determining who would reach LDA. In contrast, LC >2910/MUl or plasmablast frequency >2.85 % at baseline predicted a significantly higher DAS28 at week 24 after RTX and identified patients not achieving LDA at week 24 with sensitivity of 93.3 % and specificity of 44.8 %. CONCLUSIONS: A combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability. PMID- 27558633 TI - Improving the Production of L-Phenylalanine by Identifying Key Enzymes Through Multi-Enzyme Reaction System in Vitro. AB - L-Phenylalanine (L-Phe) is an important amino acid used in both food and medicinal applications. We developed an in vitro system that allowed a direct, quantitative investigation of phenylalanine biosynthesis in E. coli. Here, the absolute concentrations of six enzymes (AroK, AroL, AroA, AroC, PheA and TyrB) involved in the shikimate (SHIK) pathway were determined by a quantitative proteomics approach and in vitro enzyme titration experiments. The reconstitution of an in vitro reaction system for these six enzymes was established and their effects on the phenylalanine production were tested. The results showed that the yield of phenylalanine increased 3.0 and 2.1 times when the concentrations of shikimate kinase (AroL) and 5-enolpyruvoyl shikimate 3-phosphate (EPSP) synthase (AroA) were increased 2.5 times. Consistent results were obtained from in vivo via the overexpression of AroA in a phenylalanine-producing strain, and the titer of phenylalanine reached 62.47 g/l after 48 h cultivation in a 5-liter jar fermentor. Our quantitative findings provide a practical method to detect the potential bottleneck in a specific metabolic pathway to determine which gene products should be targeted to improve the yield of the desired product. PMID- 27558634 TI - A mixed methods study to examine the influence of the neighborhood social context on adolescent health service utilization. AB - BACKGROUND: While adolescents' access and utilization of health services is critical for ensuring their health, very few seek care, and if they do, it is primarily from family members, friends, or other non-formal sources of care. Examining the influence of the social context on adolescent health care seeking behaviors may provide us with a better understanding for how interventions can increase adolescents' utilization of formal health care services. METHODS: The study is based on qualitative and quantitative data collected as part of the Well Being of Adolescents in Vulnerable Environments (WAVE) study, one of the first global studies to focus on very disadvantaged urban adolescents (aged 15-19 years) across five diverse sites, which include: Baltimore (USA), Ibadan (Nigeria), Johannesburg (South Africa), New Delhi (India), and Shanghai (China). Qualitative data was based on numerous methodologies, including key informant interviews, a Photovoice exercise, community mapping, focus groups and in-depth interviews. Quantitative data was gathered from a cross-sectional Audio Computer Assisted Self Interview (ACASI) survey that was administered to approximately 450 500 adolescents per site, yielding a total of 2,393 adolescents. Respondent driven sampling was used to ensure the sample include out-of-school youth and unstably housed youth who are often underrepresented in school-based or household based samples. RESULTS: While adolescents in Baltimore, New Delhi, and Johannesburg were more likely to seek health services if they felt illness symptoms, a fairly large proportion of adolescents indicated that even when they needed health care, they didn't seek it. In Johannesburg, more than 30 % of adolescents did not seek care even when they knew it was needed. Similarly, nearly a quarter of adolescents in Baltimore and in Shanghai indicated not seeking care when needed. Qualitative data indicated that adolescents exhibited a general lack of trust in providers and often felt embarrassed or stigmatized for seeking services. Multivariate analysis revealed that perceived fear and exposure to community violence was associated with a decreased likelihood of seeking care, while adult support from the home increased adolescents' likelihood to seek care in Baltimore and Johannesburg. CONCLUSIONS: Adolescent health care seeking patterns vary substantially by setting and gender. Neighborhood and family environments are important contexts in which health seeking behaviors are shaped. Efforts to connect adolescents to health care will need to target neighborhood safety as well as trust and support among adults outside of provider settings. PMID- 27558636 TI - Discordant reporting of nonmedical opioid use: reply to letter to the editor. PMID- 27558635 TI - A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment. AB - BACKGROUND: To better evaluate and improve the efficacy of dendritic cell (DC) based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. METHODS: Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 * 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 * 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. RESULTS: No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. CONCLUSIONS: The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses. TRIAL REGISTRATION: ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005. PMID- 27558637 TI - Silkworm pupae oil exerts hypercholesterolemic and antioxidant effects in high cholesterol diet-fed rats. AB - BACKGROUND: Silkworm pupae is a good resource of edible oil that is especially rich in unsaturated fatty acids and is considered to be an excellent dietary supplement for hyperlipidemia. RESULTS: Groups fed a high-cholesterol diet (HCD) with silkworm pupae oil (SPO) supplementation (1, 2, or 4 mL kg-1 day-1 ) orally had significantly lower levels of serum total cholesterol (P < 0.05) and low density lipoprotein cholesterol (P < 0.05) compared to the HCD group. With regard to antioxidant parameters, except for levels of glutathione peroxidase (GSH-Px) in the liver, 2 and 4 mL kg-1 day-1 of SPO supplementation leaded to higher total antioxidant capacity (P < 0.05), superoxide dismutase (P < 0.05) and GSH-Px levels (P < 0.05), as well as lower malondialdehyde levels (P < 0.05), both in serum and liver compared to the HCD group. CONCLUSION: The results of the present study indicate that supplementation with SPO can improve lipid profiles and alleviate oxidative stress in high-cholesterol diet-fed rats. (c) 2016 Society of Chemical Industry. PMID- 27558638 TI - The lightest organic radical cation for charge storage in redox flow batteries. AB - In advanced electrical grids of the future, electrochemically rechargeable fluids of high energy density will capture the power generated from intermittent sources like solar and wind. To meet this outstanding technological demand there is a need to understand the fundamental limits and interplay of electrochemical potential, stability, and solubility in low-weight redox-active molecules. By generating a combinatorial set of 1,4-dimethoxybenzene derivatives with different arrangements of substituents, we discovered a minimalistic structure that combines exceptional long-term stability in its oxidized form and a record breaking intrinsic capacity of 161 mAh/g. The nonaqueous redox flow battery has been demonstrated that uses this molecule as a catholyte material and operated stably for 100 charge/discharge cycles. The observed stability trends are rationalized by mechanistic considerations of the reaction pathways. PMID- 27558639 TI - Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. AB - Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S linked sugar. Such Cys modifications have been detected and identified in mouse and rat samples. This work has established the occurrence of 14 modification sites assigned to 11 proteins unambiguously. We have also identified S GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. PMID- 27558640 TI - Ramalin Isolated from Ramalina Terebrata Attenuates Atopic Dermatitis-like Skin Lesions in Balb/c Mice and Cutaneous Immune Responses in Keratinocytes and Mast Cells. AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease that involves eczematous skin lesions with pruritic erythematous papules. In this study, we investigated the mitigating effects of ramalin, a component of the Antarctic lichen Ramalina terebrata against AD in vivo and in vitro. Oral administration of ramalin lessened scratching behaviors and significantly reduced both serum immunoglobulin E and IL-4 levels, and mRNA levels of IL-4 and IL-10 in AD-induced Balb/c mice. In vitro, treatment with ramalin produced significantly less inflammatory chemokines and cytokines, including TARC, MCP-1, RANTES, and IL-8 in TNF-alpha-stimulated HaCaT cells. In addition, ramalin inhibited the activation of nuclear factor-kappa B as well as the phosphorylation of mitogen-activated protein kinases (MAPK). Furthermore, ramalin treatment resulted in decreased production of beta-hexosaminidase and proinflammatory cytokines IL-4, IL-6, and TNF-alpha in 2,4 dinitrophenyl-human serum albumin-stimulated RBL-2H3 cells through blocking MAPK signaling pathways. The results suggest that ramalin modulates the production of immune mediators by inhibiting the nuclear factor kappa B and MAPK signaling pathways. Taken together, ramalin effectively attenuated the development of AD and promoted the mitigating effects on Th2 cell mediated immune responses and the production of inflammatory mediators in mast cells and keratinocytes. Thus, ramalin may be a potential therapeutic agent for AD. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27558641 TI - Moving Graphitic Carbon Nitride from Electrocatalysis and Photocatalysis to a Potential Electrode Material for Photoelectric Devices. AB - Carbon nitride (g-CN) has attracted significant interest in the last years as a robust, low-cost alternative to metal-based materials in different fields due to its low price, environmentally benign character, simple synthesis and tunable properties. In particular, g-CN demonstrates promising activity in energy-related applications such as photo and heterogeneous catalysis, batteries and electrolysis. However, while g-CN is already well-established as a photocatalyst, its utilization in (opto)electronic devices is still at an early stage. This Focus Review concentrates on the utilization of g-CN in solar and photoelectrochemical cells, electrolyzers and light emitting diode alongside the recap of new synthetic approaches. This review is expected to provide useful insights into the design and fabrication of g-CN based photoelectronic devices as well as g-CN working principles, including the main challenges toward its integration in optoelectronic devices. PMID- 27558642 TI - IUCD inserted after first trimester abortion: An observational study of 100 cases. PMID- 27558643 TI - Overview of Serum Uric Acid Treatment Targets in Gout: Why Less Than 6 mg/dL? AB - Gout is a progressive, painful, debilitating form of inflammatory arthritis. It is caused by factors that elevate the concentration of serum uric acid (sUA), leading to hyperuricemia (sUA >6.8 mg/dL). Continued elevated sUA can result in monosodium urate (MSU) crystal deposition in joints and soft tissues, and can cause acute and chronic inflammation. The prevalence of hyperuricemia and gout has increased over the last few decades, likely due to an aging population, changes in lifestyles and diet, and an increase in gout-associated comorbidities. Untreated or improperly treated gout can lead to chronic manifestation of the disease, including persistent inflammation, increased number of flares, development of tophi, and structural joint damage. Data show that even when patients are asymptomatic, ongoing inflammation and subsequent damage occurs locally at the joint and systemically. The aim of long-term treatment of gout is to reduce sUA levels to <6 mg/dL, which is below the saturation point of MSU (6.8 mg/dL), to inhibit formation of new crystals and to promote dissolution of existing crystals. Gout treatment should improve disease outcomes by eliminating gout flares, inducing long-term resolution of tophi, and more effectively managing comorbidities, many of which are associated with hyperuricemia. A number of studies have demonstrated that treating to the target of <6 mg/dL, by using effective therapies to lower sUA, results in reduction in the incidence of gout flares as well as shrinkage and eventual disappearance of tophi. Gout is often poorly managed due to a number of factors including lack of physician and patient adherence to treatment guidelines. Patients need to be educated about their diagnosis and management of the disease, such as the influence of diet and the importance of compliance with long-term treatment. With treatment, regular sUA monitoring, and patient adherence, gout is a curable disease. PMID- 27558645 TI - "Are these adult doctors gonna know me?" Experiences of transition for young people with a liver transplant. AB - Excellent survival rates in paediatric LTx have resulted in increasing numbers of young people transferring from paediatric to adult care. Understanding the mechanisms of successful transition is imperative for ensuring good long-term outcomes and developing services for young people. Semi-structured interviews were conducted with 17 young people (10 females; age range: 15.2-25.1 years). Eight were within 1 year of transferring to adult services; nine had transferred. Interviews were analysed using IPA. Analysis revealed two major themes in both pre- and post-transfer groups: "relationships with healthcare professionals" and "continuity of care." Young people experienced difficulty ending relationships with paediatric clinicians and forming new relationships with adult clinicians. They expressed frustrations over a perceived lack of continuity of care after transfer and a fear of the unknown nature of adult services. The importance of a holistic approach to care was emphasized. Interventions are needed to support young people in transition, particularly in ending relationships in paediatric care and forming new relationships in adult care. Young people need help to develop strategies to cope with the different approaches in adult services. Interventions to provide clinicians with skills to communicate and engage with young people are imperative. PMID- 27558644 TI - Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit. AB - A multi-subunit ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), regulates critical cellular processes including the cell cycle. To accomplish its diverse functions, APC/C activity must be precisely regulated in time and space. The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells. However, neither the mechanism of its localization nor its importance is clear. Here we identify the centrosome component Spd2 as a major partner of Fzr in Drosophila. The localization of Fzr to the centriole during interphase depends on direct interaction with Spd2. By generating Spd2 mutants unable to bind Fzr, we show that centrosomal localization of Fzr is essential for optimal APC/C activation towards its centrosomal substrate Aurora A. Finally, we show that Spd2 is also a novel APC/C(Fzr) substrate. Our study is the first to demonstrate the critical importance of distinct subcellular pools of APC/C activators in the spatiotemporal control of APC/C activity. PMID- 27558646 TI - Microglia contact induces synapse formation in developing somatosensory cortex. AB - Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8-10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca(2+) transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction. PMID- 27558647 TI - Impact of area strain by 3D speckle tracking on clinical outcome in patients after acute myocardial infarction. AB - BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) has been developed to overcome the limitations of two-dimensional (2D) STE and has been applied in the several clinical settings. However, no data exist about the prognostic value of 3DSTE-based strain on clinical outcome after myocardial infarction (MI). This study was designed to investigate the prognostic value of area strain (AS) by 3D speckle tracking in predicting clinical outcome after acute MI. METHODS: We assessed 96 patients (62+/-14 years, 72% male) with acute MI and who had undergone a coronary angiography. Clinical parameters and conventional echocardiographic measurements including the left atrial (LA) size and tissue Doppler measurements were evaluated. The global left ventricular (LV) AS was measured using 3D speckle tracking software. The relationship between the AS and clinical outcome of death or hospitalization for heart failure (HF) was assessed. RESULTS: During a median follow-up of 33+/-10 months, primary endpoint of death or HF occurred in 12 patients (12.5%). AS was predictive of death or HF after adjustment for age, gender, peak CK-MB, LA volume, LV end-systolic volume, LV mass, the ratio of early mitral inflow velocity to early mitral annular velocity, and LV ejection fraction in a multivariate Cox model (HR 1.23, 95% CI 1.02-1.47, P=.03). In addition, AS added incremental value in predicting death or heart failure on a model based on clinical and standard echocardiographic measures (P=.008). CONCLUSION: AS is independently associated with increased risk of death or HF after acute MI, suggesting that it can be a useful prognostic parameter in the patients following MI. PMID- 27558648 TI - Binge-type eating disrupts dopaminergic and GABAergic signaling in the prefrontal cortex and ventral tegmental area. AB - OBJECTIVE: Binge eating is characterized by repeated intermittent bouts of compulsive overconsumption of food. Treatment is challenging given limited understanding of the mechanisms underlying this type of disordered eating. The hypothesis that dysregulation of mesocortical dopaminergic and GABAergic systems underlie binge eating was tested. METHODS: Analysis of gene expression within the ventral tegmental area and its terminal mesocortical regions was examined in bingeing rats before and after bingeing occurred. In addition, alterations in binge-type behavior induced by pharmacological inactivation of subnuclei of the prefrontal cortex (PFC) and by pharmacological activation and inhibition of cortical D1 and D2 receptors were examined. RESULTS: Correlative and functional evidence demonstrates dysregulated neurotransmitter processing by the PFC and ventral tegmental area, but not the amygdala or nucleus accumbens, in bingeing rats. Either GABAergic inactivation or D2-like receptor activation within the PFC increased consumption in bingeing rats, but not controls, suggesting that the PFC, and D2 receptors in particular, functions as a behavioral brake to limit bingeing. CONCLUSIONS: The act of bingeing resolved some gene expression differences that preceded binge onset, further suggesting that bingeing may partially serve to self-medicate a system driving this maladaptive behavior. However, the failure of bingeing to resolve other dopaminergic/GABAergic differences may render individuals vulnerable to future binge episodes. PMID- 27558649 TI - Combined Expression of c-jun, c-fos, and p53 Improves Estimation of Prognosis in Oral Squamous Cell Carcinoma. AB - To identify the prognostic value of c-jun, c-fos, and p53 in oral cancer, we examined the impact of immunohistochemical expression of these markers on tumor progression in 157 oral squamous cell carcinoma (OSCC). We found that c-jun or c fos was significantly associated with lymph node metastasis, and coexpression of c-jun/c-fos, or c-jun/c-fos/p53 were significantly associated with lymph node metastasis, poor differentiation and clinical stage. The coexpression of c-jun/c fos/p53 was identified as independent prognostic factors for overall survival. Simultaneous coexpression of these markers in OSCCs might prove to be a useful indicator for differentiation of low and high-risk patients. PMID- 27558650 TI - Topology of chromosome centromeres in human sperm nuclei with high levels of DNA damage. AB - Several studies have shown that the 'poor' sperm DNA quality appears to be an important factor affecting male reproductive ability. In the case of sperm cells from males with the correct somatic karyotype but with deficient spermatogenesis, resulting in a high degree of sperm DNA fragmentation, we observed changes in the preferential topology of the chromosome 7, 9, 15, 18, X and Y centromeres. The changes occurred in radial localization and may have been directly linked to the sperm chromatin damage. This conclusion is mainly based on a comparison of FISH signals that were observed simultaneously in the TUNEL-positive and TUNEL negative sperm cells. The analyzed cells originated from the same ejaculated sample and FISH was performed on the same slides, after in situ TUNEL reaction. Based on the observed changes and previous data, it appears that the sperm nucleus architecture can be disrupted by a variety of factors and has a negative influence on spermatogenesis at the same time. Often, these factors coexist (e.g. chromosomal translocations, aneuploidies, a higher DNA fragmentation, abnormal seminology), but no direct correlations between the factors were observed. PMID- 27558651 TI - Accounting for measurement error in biomarker data and misclassification of subtypes in the analysis of tumor data. AB - A common paradigm in dealing with heterogeneity across tumors in cancer analysis is to cluster the tumors into subtypes using marker data on the tumor, and then to analyze each of the clusters separately. A more specific target is to investigate the association between risk factors and specific subtypes and to use the results for personalized preventive treatment. This task is usually carried out in two steps-clustering and risk factor assessment. However, two sources of measurement error arise in these problems. The first is the measurement error in the biomarker values. The second is the misclassification error when assigning observations to clusters. We consider the case with a specified set of relevant markers and propose a unified single-likelihood approach for normally distributed biomarkers. As an alternative, we consider a two-step procedure with the tumor type misclassification error taken into account in the second-step risk factor analysis. We describe our method for binary data and also for survival analysis data using a modified version of the Cox model. We present asymptotic theory for the proposed estimators. Simulation results indicate that our methods significantly lower the bias with a small price being paid in terms of variance. We present an analysis of breast cancer data from the Nurses' Health Study to demonstrate the utility of our method. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27558653 TI - Effects of donor cells' sex on nuclear transfer efficiency and telomere lengths of cloned goats. AB - The aim of this study was to investigate the effects of donor cells' sex on nuclear transfer efficiency and telomere length of cloned goats from adult skin fibroblast cells. The telomere length of somatic cell cloned goats and their offspring was determined by measuring their mean terminal restriction fragment (TRF) length. The result showed that (i) reconstructed embryos with fibroblast cells from males Boer goats obtained significantly higher kids rate and rate of live kids than those of female embryos and (ii) the telomere lengths of four female cloned goats were shorter compared to their donor cells, but five male cloned goats had the same telomere length with their donor cells, mainly due to great variation existed among them. The offspring from female cloned goats had the same telomere length with their age-matched counterparts. In conclusion, the donor cells' sex had significant effects on nuclear transfer efficiency and telomere lengths of cloned goats. PMID- 27558654 TI - Oral iron supplementation with sodium ferrous citrate reduces the serum intact and c-terminal fibroblast growth factor 23 levels of maintenance haemodialysis patients. AB - AIM: Iron deficiency stimulates fibroblast growth factor 23 (FGF23) transcription. This study aimed to determine whether oral ferrous iron (Fe2+ ) reduces the serum FGF23 levels of iron-deficient maintenance haemodialysis (MHD) patients in the same way as oral ferric iron (Fe3+ ) METHODS: Thirty-one MHD patients with iron deficiency were enrolled in this prospective study. Patients who had taken iron supplements during the 8 weeks before the study were excluded. The patients' iron stores and their serum FGF23, phosphate, intact parathyroid hormone (iPTH), albumin, C-reactive protein (CRP), and albumin-adjusted calcium (Ca) levels were examined at the baseline and after 3 months' treatment with sodium ferrous citrate (Fe2+ ). RESULTS: The patients' transferrin saturation values and serum iron and ferritin levels were significantly increased after 3 months' treatment (P < 0.01), as were their serum albumin levels (P < 0.05). Conversely, their serum intact FGF23 (iFGF23) [1820 (342-4370) vs 1240 (214-2940) pg/mL, P < 0.05], C-terminal FGF23 (cFGF23) [309 (120-1211) vs 259 (99-600) pg/mL, P < 0.05)], and CRP levels (P < 0.01) were significantly reduced after 3 months' treatment. No changes were detected in the patients' serum iFGF23:cFGF23 ratios or their serum phosphate, Ca, or iPTH levels. The changes in the patients' serum iFGF23 and cFGF23 levels induced by sodium ferrous citrate supplementation were shown to be attributable to changes in their serum ferritin levels (P < 0.05). CONCLUSION: Short-term oral iron supplementation with sodium ferrous citrate replenished the iron stores and reduced the serum iFGF23 and cFGF23 levels of MHD patients with iron deficiency without affecting their serum phosphate, Ca, or iPTH levels. PMID- 27558655 TI - Reliable Digital Single Molecule Electrochemistry for Ultrasensitive Alkaline Phosphatase Detection. AB - Single molecule electrochemistry (SME) has gained much progress in fundamental studies, but it is difficult to use in practice due to its less reliability. We have solved the reliability of single molecule electrochemical detection by integration of digital analysis with efficient signal amplification of enzyme induced metallization (EIM) together with high-throughput parallelism of microelectrode array (MA), establishing a digital single molecule electrochemical detection method (dSMED). Our dSMED has been successfully used for alkaline phosphatase (ALP) detection in the complex sample of liver cancer cells. Compared to direct measurement of the oxidation current of enzyme products, EIM can enhance signals by about 100 times, achieving signal-to-background ratio high enough for single molecule detection. The integration of digital analysis with SME can further decrease the detection limit of ALP to 1 aM relative to original 50 aM, enabling dSMED to be sensitively, specifically and reliably applied in liver cancer cells. The presented dSMED is enormously promising in exploring physical and chemical properties of single molecules, single biomolecular detection, or single-cell analysis. PMID- 27558652 TI - Wedelolactone enhances osteoblastogenesis by regulating Wnt/beta-catenin signaling pathway but suppresses osteoclastogenesis by NF-kappaB/c-fos/NFATc1 pathway. AB - Bone homeostasis is maintained by formation and destruction of bone, which are two processes tightly coupled and controlled. Targeting both stimulation on bone formation and suppression on bone resorption becomes a promising strategy for treating osteoporosis. In this study, we examined the effect of wedelolactone, a natural product from Ecliptae herba, on osteoblastogenesis as well as osteoclastogenesis. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone stimulated osteoblast differentiation and bone mineralization. At the molecular level, wedelolactone directly inhibited GSK3beta activity and enhanced the phosphorylation of GSK3beta, thereafter stimulated the nuclear translocation of beta-catenin and runx2. The expression of osteoblastogenesis related marker gene including osteorix, osteocalcin and runx2 increased. At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. Further, wedelolactone blocked NF-kB/p65 phosphorylation and abrogated the NFATc1 nuclear translocation. As a result, osteoclastogenesis-related marker gene expression decreased, including c-src, c-fos, and cathepsin K. In ovariectomized mice, administration of wedelolactone prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. Together, these data demonstrated that wedelolactone facilitated osteoblastogenesis through Wnt/GSK3beta/beta catenin signaling pathway and suppressed RANKL-induced osteoclastogenesis through NF-kappaB/c-fos/NFATc1 pathway. These results suggested that wedelolacone could be a novel dual functional therapeutic agent for osteoporosis. PMID- 27558656 TI - Rare Presentation of Gastroesophageal Carcinoma with Rectal Metastasis: A Case Report. AB - BACKGROUND Gastroesophageal cancers, previously considered rare, are rapidly increasing worldwide. We present here a unique case of gastroesophageal carcinoma with metastasis to the rectum. CASE REPORT A 60-year-old female patient presented with constipation, bloating, and weight loss of 4-month duration. She had undergone sleeve gastrectomy 6 years before. Endoscopies performed revealed a friable-looking mucosa in the lower esophagus and a polypoid rectal mass. Histopathological examination from both the esophageal and rectal lesions revealed poorly differentiated adenocarcinoma cells. Immunohistochemistry stain from both specimens was positive for CK7 supporting the gastric site primary with metastasis to the rectum. Further evaluation also revealed metastasis to bone and malignant pleural effusion. Chemotherapy with palliative intent was initiated. CONCLUSIONS Colorectal metastasis is commonly seen from cancers of the breast, stomach, melanoma, kidney, prostate, and ovaries. However, colorectal metastasis from gastroesophageal cancer has never been reported in the medical literature. Diagnosis relies on histopathologic examination and immunohistochemical staining of the tumor. Treatment depends on the tumor stage. Tumors with widespread metastatic disease are candidates for palliative chemotherapy. PMID- 27558657 TI - Vasculitis syndromes: Diagnostic and prognostic roles for T-cell markers in Kawasaki disease. PMID- 27558658 TI - Inflammatory myopathies: NK cell function linked to antisynthetase syndrome. PMID- 27558660 TI - Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons. AB - Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death, and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons. PMID- 27558661 TI - Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients. AB - We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules. PMID- 27558662 TI - An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose. AB - BACKGROUND: Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. METHODS: A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. RESULTS: Ninety samples were collected. There was a variation of <=10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml-1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml-1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml-1 (-0.6 to +0.2) for third and fourth infusions. CONCLUSION: There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. PMID- 27558659 TI - The global burden of SLE: prevalence, health disparities and socioeconomic impact. AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can potentially lead to serious organ complications and even death. Its global burden - in terms of incidence and prevalence, differential impact on populations, economic costs and capacity to compromise health-related quality of life - remains incompletely understood. The reported worldwide incidence and prevalence of SLE vary considerably; this variation is probably attributable to a variety of factors, including ethnic and geographic differences in the populations being studied, the definition of SLE applied, and the methods of case identification. Despite the heterogeneous nature of the disease, distinct patterns of disease presentation, severity and course can often be related to differences in ethnicity, income level, education, health insurance status, level of social support and medication compliance, as well as environmental and occupational factors. Given the potential for the disease to cause such severe and widespread organ damage, not only are the attendant direct costs high, but these costs are sometimes exceeded by indirect costs owing to loss of economic productivity. As an intangible cost, patients with SLE are, not surprisingly, likely to endure considerably reduced health-related quality of life. PMID- 27558663 TI - Obp56h Modulates Mating Behavior in Drosophila melanogaster. AB - Social interactions in insects are driven by conspecific chemical signals that are detected via olfactory and gustatory neurons. Odorant binding proteins (Obps) transport volatile odorants to chemosensory receptors, but their effects on behaviors remain poorly characterized. Here, we report that RNAi knockdown of Obp56h gene expression in Drosophila melanogaster enhances mating behavior by reducing courtship latency. The change in mating behavior that results from inhibition of Obp56h expression is accompanied by significant alterations in cuticular hydrocarbon (CHC) composition, including reduction in 5-tricosene (5 T), an inhibitory sex pheromone produced by males that increases copulation latency during courtship. Whole genome RNA sequencing confirms that expression of Obp56h is virtually abolished in Drosophila heads. Inhibition of Obp56h expression also affects expression of other chemoreception genes, including upregulation of lush in both sexes and Obp83ef in females, and reduction in expression of Obp19b and Or19b in males. In addition, several genes associated with lipid metabolism, which underlies the production of cuticular hydrocarbons, show altered transcript abundances. Our data show that modulation of mating behavior through reduction of Obp56h is accompanied by altered cuticular hydrocarbon profiles and implicate 5-T as a possible ligand for Obp56h. PMID- 27558664 TI - Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast. AB - Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5'-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt-Ada-Gcn5 acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms. PMID- 27558665 TI - An Eye on Trafficking Genes: Identification of Four Eye Color Mutations in Drosophila. AB - Genes that code for proteins involved in organelle biogenesis and intracellular trafficking produce products that are critical in normal cell function . Conserved orthologs of these are present in most or all eukaryotes, including Drosophila melanogaster Some of these genes were originally identified as eye color mutants with decreases in both types of pigments found in the fly eye. These criteria were used for identification of such genes, four eye color mutations that are not annotated in the genome sequence: chocolate, maroon, mahogany, and red Malpighian tubules were molecularly mapped and their genome sequences have been evaluated. Mapping was performed using deletion analysis and complementation tests. chocolate is an allele of the VhaAC39-1 gene, which is an ortholog of the Vacuolar H+ ATPase AC39 subunit 1. maroon corresponds to the Vps16A gene and its product is part of the HOPS complex, which participates in transport and organelle fusion. red Malpighian tubule is the CG12207 gene, which encodes a protein of unknown function that includes a LysM domain. mahogany is the CG13646 gene, which is predicted to be an amino acid transporter. The strategy of identifying eye color genes based on perturbations in quantities of both types of eye color pigments has proven useful in identifying proteins involved in trafficking and biogenesis of lysosome-related organelles. Mutants of these genes can form the basis of valuable in vivo models to understand these processes. PMID- 27558666 TI - Head Transcriptomes of Two Closely Related Species of Fruit Flies of the Anastrepha fraterculus Group Reveals Divergent Genes in Species with Extensive Gene Flow. AB - Several fruit flies species of the Anastrepha fraterculus group are of great economic importance for the damage they cause to a variety of fleshy fruits. Some species in this group have diverged recently, with evidence of introgression, showing similar morphological attributes that render their identification difficult, reinforcing the relevance of identifying new molecular markers that may differentiate species. We investigated genes expressed in head tissues from two closely related species: A. obliqua and A. fraterculus, aiming to identify fixed single nucleotide polymorphisms (SNPs) and highly differentiated transcripts, which, considering that these species still experience some level of gene flow, could indicate potential candidate genes involved in their differentiation process. We generated multiple libraries from head tissues of these two species, at different reproductive stages, for both sexes. Our analyses indicate that the de novo transcriptome assemblies are fairly complete. We also produced a hybrid assembly to map each species' reads, and identified 67,470 SNPs in A. fraterculus, 39,252 in A. obliqua, and 6386 that were common to both species. We identified 164 highly differentiated unigenes that had a mean interspecific index ([Formula: see text]) of at least 0.94. We selected unigenes that had Ka/Ks higher than 0.5, or had at least three or more highly differentiated SNPs as potential candidate genes for species differentiation. Among these candidates, we identified proteases, regulators of redox homeostasis, and an odorant-binding protein (Obp99c), among other genes. The head transcriptomes described here enabled the identification of thousands of genes hitherto unavailable for these species, and generated a set of candidate genes that are potentially important to genetically identify species and understand the speciation process in the presence of gene flow of A. obliqua and A. fraterculus. PMID- 27558667 TI - Evaluation of Ligand-Inducible Expression Systems for Conditional Neuronal Manipulations of Sleep in Drosophila. AB - Drosophila melanogaster is a powerful model organism for dissecting the molecular mechanisms that regulate sleep, and numerous studies in the fly have identified genes that impact sleep-wake cycles. Conditional genetic analysis is essential to distinguish the mechanisms by which these genes impact sleep: some genes might exert their effects developmentally, for instance by directing the assembly of neuronal circuits that regulate sleep; other genes may regulate sleep in adulthood; and yet other genes might influence sleep by both developmental and adult mechanisms. Here we have assessed two ligand-inducible expression systems, Geneswitch and the Q-system, for conditional and neuronally restricted manipulations of sleep in Drosophila While adult-specific induction of a neuronally expressed Geneswitch transgene (elav-GS) is compatible with studies of sleep as shown previously, developmental induction of elav-GS strongly and nonspecifically perturbs sleep in adults. The alterations of sleep in elav-GS animals occur at low doses of Geneswitch agonist and in the presence of transgenes unrelated to sleep, such as UAS-CD8-GFP Furthermore, developmental elav-GS induction is toxic and reduces brood size, indicating multiple adverse effects of neuronal Geneswitch activation. In contrast, the transgenes and ligand of the Q-system do not significantly impact sleep-wake cycles when used for constitutive, developmental, or adult-specific neuronal induction. The nonspecific effects of developmental elav-GS activation on sleep indicate that such manipulations require cautious interpretation, and suggest that the Q-system or other strategies may be more suitable for conditional genetic analysis of sleep and other behaviors in Drosophila. PMID- 27558668 TI - Seizure Suppression by High Temperature via cAMP Modulation in Drosophila. AB - Bang-sensitive (BS) Drosophila mutants display characteristic seizure-like activity (SLA) and paralysis after mechanical shock . After high-frequency electrical stimulation (HFS) of the brain, they generate robust seizures at very low threshold voltage. Here we report an important phenomenon, which effectively suppresses SLA in BS mutants. High temperature causes seizure suppression in all BS mutants (parabss1, eas, sda) examined in this study. This effect is fully reversible and flies show complete recovery from BS paralysis once the temperature effect is nullified. High temperature induces an increase in seizure threshold after a brief pulse of heat shock (HS). By genetic screening, we identified the involvement of cAMP in the suppression of seizures by high temperature. We propose that HS induces adenylyl cyclase which in turn increases cAMP concentration which eventually suppresses seizures in mutant flies. In summary, we describe an unusual phenomenon, where high temperature can suppress SLA in flies by modulating cAMP concentration. PMID- 27558669 TI - Preservation Analysis of Macrophage Gene Coexpression Between Human and Mouse Identifies PARK2 as a Genetically Controlled Master Regulator of Oxidative Phosphorylation in Humans. AB - Macrophages are key players involved in numerous pathophysiological pathways and an in-depth characterization of their gene regulatory networks can help in better understanding how their dysfunction may impact on human diseases. We here conducted a cross-species network analysis of macrophage gene expression data between human and mouse to identify conserved networks across both species, and assessed whether such networks could reveal new disease-associated regulatory mechanisms. From a sample of 684 individuals processed for genome-wide macrophage gene expression profiling, we identified 27 groups of coexpressed genes (modules). Six modules were found preserved (P < 10-4) in macrophages from 86 mice of the Hybrid Mouse Diversity Panel. One of these modules was significantly [false discovery rate (FDR) = 8.9 * 10-11] enriched for genes belonging to the oxidative phosphorylation (OXPHOS) pathway. This pathway was also found significantly (FDR < 10-4) enriched in susceptibility genes for Alzheimer, Parkinson, and Huntington diseases. We further conducted an expression quantitative trait loci analysis to identify SNP that could regulate macrophage OXPHOS gene expression in humans. This analysis identified the PARK2 rs192804963 as a trans-acting variant influencing (minimal P-value = 4.3 * 10-8) the expression of most OXPHOS genes in humans. Further experimental work demonstrated that PARK2 knockdown expression was associated with increased OXPHOS gene expression in THP1 human macrophages. This work provided strong new evidence that PARK2 participates to the regulatory networks associated with oxidative phosphorylation and suggested that PARK2 genetic variations could act as a trans regulator of OXPHOS gene macrophage expression in humans. PMID- 27558670 TI - A Genome-Wide Association Study Identifies Multiple Regions Associated with Head Size in Catfish. AB - Skull morphology is fundamental to evolution and the biological adaptation of species to their environments. With aquaculture fish species, head size is also important for economic reasons because it has a direct impact on fillet yield. However, little is known about the underlying genetic basis of head size. Catfish is the primary aquaculture species in the United States. In this study, we performed a genome-wide association study using the catfish 250K SNP array with backcross hybrid catfish to map the QTL for head size (head length, head width, and head depth). One significantly associated region on linkage group (LG) 7 was identified for head length. In addition, LGs 7, 9, and 16 contain suggestively associated regions for head length. For head width, significantly associated regions were found on LG9, and additional suggestively associated regions were identified on LGs 5 and 7. No region was found associated with head depth. Head size genetic loci were mapped in catfish to genomic regions with candidate genes involved in bone development. Comparative analysis indicated that homologs of several candidate genes are also involved in skull morphology in various other species ranging from amphibian to mammalian species, suggesting possible evolutionary conservation of those genes in the control of skull morphologies. PMID- 27558672 TI - Antifungal activity of fabricated mesoporous alumina nanoparticles against root rot disease of tomato caused by Fusarium oxysporium. AB - BACKGROUND: The present work involved the synthesis and characterisation of mesoporous alumina sphere (MAS) nanoparticles to evaluate their biological activity against tomato root rot caused by Fusarium oxysporium, as compared with the recommended fungicide, tolclofos-methyl, under laboratory and greenhouse conditions. The effects of MAS nanoparticles on the growth of tomato plants were also evaluated and compared with those of tolclofos-methyl. RESULTS: The physical characteristics and structural features of MAS nanoparticles, such as their large surface-area-to-volume ratio, active surface sites and open channel pores, caused high antifungal efficacy against F. oxysporium. MAS nanoparticles presented an antifungal potential similar to that of tolclofos-methyl and much greater than that of the control under both laboratory and greenhouse conditions. The highest growth parameters were recorded in tomato plants treated with MAS nanoparticles, followed by those treated with tolclofos-methyl. CONCLUSIONS: Our study demonstrated the possible use of cylindrically cubic MAS nanoparticles as an effective alternative for the control of Fusarium root rot in tomato. (c) 2016 Society of Chemical Industry. PMID- 27558671 TI - Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone. AB - KEY POINTS: Loss of function of the melanocortin 4 receptor (MC4R) results in hyperphagia, obesity and increased growth. Despite knowing that MC4Rs control food intake, we are yet to understand why defects in the function of the MC4R receptor contribute to rapid linear growth. We show that hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis. We propose that hyperinsulinaemia promotes growth while suppressing the GH-IGF-1 axis. It is argued that physiological responses essential to maintain energy flux override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. ABSTRACT: Defects in melanocortin-4-receptor (MC4R) signalling result in hyperphagia, obesity and increased growth. Clinical observations suggest that loss of MC4R function may enhance growth hormone (GH) mediated growth, although this remains untested. Using male mice with germline loss of the MC4R, we assessed pulsatile GH release and insulin-like growth factor 1 (IGF-1) production and/or release relative to pubertal growth. We demonstrate early-onset suppression of GH release in rapidly growing MC4R deficient (MC4RKO) mice, confirming that increased linear growth in MC4RKO mice does not occur in response to enhanced activation of the GH-IGF-1 axis. The progressive suppression of GH release in MC4RKO mice occurred alongside increased adiposity and the progressive worsening of hyperphagia-associated hyperinsulinaemia. We next prevented hyperphagia in MC4RKO mice through restricting calorie intake in these mice to match that of wild-type (WT) littermates. Pair feeding of MC4RKO mice did not prevent increased adiposity, but attenuated hyperinsulinaemia, recovered GH release, and normalized linear growth rate to that seen in pair-fed WT littermate controls. We conclude that the suppression of GH release in MC4RKO mice occurs independently of increased adipose mass, and is a consequence of hyperphagia associated hyperinsulinaemia. It is proposed that physiological responses essential to maintain energy flux (hyperinsulinaemia and the suppression of GH release) override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Implications of these findings are likely to extend beyond individuals with defects in MC4R signalling, encompassing physiological changes central to mechanisms of growth and energy homeostasis universal to hyperphagia-associated childhood-onset obesity. PMID- 27558673 TI - New Adamantyl Chalcones: Synthesis, Antimicrobial and Anticancer Activities. AB - BACKGROUND: A new variety of adamantyl chalcones (2, 3a-o) were efficiently prepared by Claisen-Schmidt reaction of 4-adamantyl acetophenone 2 with a serie of aromatic aldehydes in good yields. Their structures were confirmed by spectroscopic data, and the relative configuration of 3d was confirmed by X-ray crystallography. All synthesized chalcones were tested against a panel of Grampositive and Gram-negative bacteria and pathogenic fungus and displayed strong antibacterial activity against Enterococcus faecali 29212, Pseudomonas aeruginosa ATCC27853, Escherichia coli and interesting antifungal activity against Candida glabrata ATCC 90030. RESULT: The effect of these compounds was also tested in vitro as antitumor on Miapaca2 cells. Compounds also showed anticancer activity against human pancreas cancer cell MiaPaca2. PMID- 27558674 TI - A Medical Approach to the Monoamine Oxidase Inhibition by Using 7Hbenzo[ e]perimidin-7-one Derivatives. AB - BACKGROUND: A series of perimidinone derivatives (7H-benzo[e]perimidin-7-one) were synthesized and assessed by means of in vitro assays as human MAO inhibitors. These compounds inhibited reversibly the enzymes with inhibitory constants in the range of 2 to 20 MUM. In addition, the selectivity of inhibition of the MAO isoforms seems to be significantly dependent of the presence either of heteroatom or electron donating and withdrawing groups on the perimidinone framework, which was verified by using molecular docking simulation with the crystallized MAO receptors. Most of these inhibitors were highly selective: 9 and 11 inhibited selectively the MAO-B isoform while 12 had 10-fold selectivity for MAO-A isoform. Moreover, the compound 12 was both the most selective and potent MAO-A inhibitor among perimidinones. RESULT: These results have important implications for the drug design of molecules targeting depression and movement related disorders. PMID- 27558675 TI - Melatonin and Respiratory Diseases: A Review. AB - Melatonin is an indoleamine with potent multifunctional biological and pharmacological effects, both receptor dependent and receptor-independent effects, including antioxidant, anticancer, antitumor, anti-inflammatory, anti aging, anti-diabetic, antiviral, neuroprotective activities. Melatonin mitigates tissue injury via modification of abnormalities in redox status and other biochemical markers. At the molecular level, the biological and pharmacological activities of melatonin are attributed to the inhibition of nuclear factor kappaappa beta (NF-kappabeta), c-Fos over expression and down-regulation of matrix metalloproteinases-3 (MMP-3), which are regulators of pro-inflammatory and pro-fibrotic cytokines. There are numerous scientific reports on the therapeutic potential of melatonin in treatment of asthma, respiratory diseases for infections, chronic obstructive pulmonary disease, lung cancer, pleural cavity diseases, as well as vascular pulmonary disease. In the present communication, we systematically review the therapeutic potential of melatonin in the treatment of respiratory diseases along with its molecular mechanism of actions. PMID- 27558676 TI - Flavonoids and Chagas' Disease: The Story So Far! AB - Chagas disease is one of the major health problems in Central and South America, which is caused by the parasitic protozoa, Trypanosoma cruzi. It is commonly transmitted by members of blood-sucking subfamily Triatominae. Chagas disease is associated with cardiac and gastrointestinal manifestations. Up to now, there are no effective vaccines for treatment of Chagas disease and benznidazole and nifurtimox are the only effective anti-Chagas drugs that cause different adverse and side effects. Therefore, much attention has been paid to natural products as novel therapeutic strategies for Chagas disease and its manifestations. Nowadays, some flavonoids could be considered as effective and safe bioactive natural products with potential anti-Chagas activity. Despite the increasing evidence, there is lack of review papers regarding the beneficial effects of flavonoids against Chagas disease and its manifestations. The aim of this paper is to review the available scientific data on the beneficial effects of flavonoids on Chagas disease and its manifestations published over the past two decades. Moreover, we provide an overview on etiology, transmission, epidemiology, clinical manifestations, and current treatment protocols of Chagas disease. PMID- 27558677 TI - Benzodiazepine Scaffold as Drug-like Molecular Simplification of FR235222: A Chemical Tool for Exploring HDAC Inhibition. AB - BACKGROUND: Synthesis, computational study and biological evaluation of peptidomimetic analogues of FR235222 (3), a natural immunosuppressant and HDAC inhibitor, have been reported. These new compounds, bearing alpha-hydroxyketone moiety, as more stable zinc binding group (ZBG), were evaluated in vitro as HDAC inhibitors against the human HDACs isoforms 1-9 and in cellular antiproliferative assays on U937 human leukemia cell line. The 1,4-benzodiazepin-2,5-dione (BDZ), capping group and the natural ZBG, (S,R)-2-amino-9-hydroxy-8-oxodecanoic acid (Ahoda), were evaluated in order to probe HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed an interesting activity against a number of HDAC isozymes. The observed activity profile was rationalized by a computational assisted SAR study, in order to understand how the BDZ classes interact with the enzyme into the catalytic pocket. Despite its poor solubility, compound 17b showed significant antiproliferative profile and HDAC inhibition activity. RESULT: In order to assess how the solubility issue could have affected the biological outcome, bioassay conditions were reproduced and quantification of precipitated particulate material was evaluated by turbidimetric and NMR studies together with physicochemical descriptors prediction. Thus, BDZ 17b has been chosen to be promising lead compounds for further optimization, in order to elucidate molecule- enzyme surface recognition. PMID- 27558678 TI - Heterocyclic Compounds: Effective alpha-Amylase and alpha-Glucosidase Inhibitors. AB - Diabetes Mellitus (DM) is a metabolic disease characterized by high blood sugar levels. Recently, it has emerged as an important and global health problem with long-term complications and high economic burden. alpha-Amylase (alpha-Amy) and alpha-glucosidase (alpha-Gls) are two enzymes which are involved in the hydrolysis of starch into sugars and disaccharides leading to the increase of blood glucose level. Hence, inhibition of alpha-amylase and alpha-glucosidase plays key role in the treatment of type 2 diabetes. Heterocyclic compounds -both synthetic and naturally occurring derivatives- possess efficient biological properties. At this juncture, they have demonstrated potent inhibitory activity against alpha-Amy and alpha-Gls and were found to be versatile tools for the development of novel anti-diabetic agents. PMID- 27558679 TI - Heterocyclic Amaryllidaceae Alkaloids: Biosynthesis and Pharmacological Applications. AB - Amaryllidaceae alkaloids (AAs), which are natural heterocyclic compounds, are isolated from Amaryllidaceae plants such as narcissus, snowdrop and spider lily. AAs have been extensively studied due to their multiple pharmacological properties. Nevertheless, knowledge of AA synthesis in plants is lacking and most genes encoding enzymes involved in their production remain unknown. AAs are structurally complex compounds which are challenging for total chemical synthesis that is economically viable. Therefore the understanding of AA biosynthesis could allow for the development of biotechnologies for the production of natural AAs or analogues, maintaining or improving their pharmacological properties. In this review, we describe the progress regarding the biosynthesis and pharmacological properties of AAs. The most recent developments in neurological, anti-cancer and anti-microbial bioactivities of heterocyclic AAs are covered. PMID- 27558680 TI - Elucidation of Phosphodiesterase-1 Inhibitory Effect of Some Selected Natural Polyphenolics Using In Vitro and In Silico Methods. AB - BACKGROUND: Polyphenols are organic compounds widely found in plants and possess many diverse biological activities. In the current study, eleven polyphenolic compounds [rutin (1), trans-ferulic acid (2), epigallaocatechin gallate (3), fumaric acid (4), chlorogenic acid (5), gallic acid (6), trans-resveratrol (7), propyl gallate (8), (+)-catechin (9), quercetin (10), and kaempferol-3-O-beta-D galactoside (11)] have been evaluated for their in vitro inhibitory activity against phosphodiesterase- 1 (PDE-1). The active compounds 1, 5, 6, and 7 possessed IC50 values of 173.90 +/- 2.58, 36.67 +/- 1.60, 325.19 +/- 3.62, and 323.81 +/- 4.25 MUM, respectively. In silico experiments were performed to elucidate the binding patterns of inhibitor molecules with the active sites of the enzymes. RESULT: Molecular docking studies have shown that compounds 1 and 5 have better docking results than standard inhibitor (EDTA) against the PDE-1. In conclusion, chlorogenic acid, rutin, gallic acid, and resveratrol could be promising PDE-1 inhibitors and leads to identify new drug candidates against PDE 1-associated disorders. PMID- 27558681 TI - Evaluation of the Novel Antichagasic Activity of [1,2,3]Triazolo[1,5-a]pyridine Derivatives. AB - BACKGROUND: Trypanosoma cruzi is the causative agent of Chagas disease. This parasite is vulnerable to the effects of ROS as its main defense mechanism against exogenous agents trypanothione is also another weakness of the parasite that investigated related to the inhibition of enzymes belonging P450 system, mainly CYP51. In our group we have synthesized a series of triazoles known as [1,2,3]triazolo[1,5-a]pyridyl ketones, and pyridyl ketones. These families have shown interesting structural features due to the presence of electron withdrawing moieties attached to the main heterocycle (triazoles and/or pyridines) and are proposed as potential target in the parasite, by the presence of the carbonyl group being able to be reduced and form a free radical that could interact with molecular oxygen generating ROS in the parasite. Furthermore, the triazole ring and pyridines have been considered as potent inhibitors of sterol biosynthesis, the lock being part CYP51. RESULT: Our results showed that the series is capable of generating a stable radical species and generate ROS in the parasite. On the other hand these molecules are potent inhibitors of enzymes belonging to the complex P450. We have focused on the inhibition of ergosterol biosynthesis demonstrating that triazole/ pyridine families are able to affect this pathway being observed the accumulation of squalene and lanosterol. PMID- 27558682 TI - Coumarin and Derivates as Lipid Lowering Agents. AB - Cardiovascular disease is the main cause of death in the developed countries. Dyslipidaemia is one of the risk factors associated to cardiovascular disease and it is characterised by abnormal amounts of lipids (i.e. cholesterol and fatty acids) and/or circulating lipoproteins in the blood. Oxidative stress has been implicated in the pathogenesis of various illnesses including cardiovascular disease. In this way, the potential therapeutic or preventive effects of antioxidant mediators have recently drawn much attention. Coumarin (1,2 benzopyrone) is a natural phenolic compound found in many plants such as citrus fruits, tomatoes, vegetables and green tea. Coumarin and derivates are proposed as lipid lowering agents due to its broad pharmacological activities, mainly the implicated in vasodilator and antioxidant effect. Several studies have evidenced a promising role of coumarin and several of its derivates as lipid lowering agents. In the current work, the available reports related to the promising function of these compounds are reviewed. PMID- 27558683 TI - Mechanisms Underlying Anti-hyperalgesic Properties of Kaempferol-3,7- di-O-alpha L-rhamnopyranoside Isolated from Dryopteris cycadina. AB - BACKGROUND: The present study was designed to evaluate the anti-hyperalgesic effect of kaempferol-3,7-di-O-alpha-L-rhamnopyranoside isolated from the ethyl acetate soluble part of Dryopteris cycadina. Pretreatment of the compound at the doses of 2.5, 5, and 10 mg/kg caused a significant reduction in abdominal constrictions in acetic acid-induced writhing test with maximum effect of 63.03% (P < 0.001) at 10 mg/kg i.p. When subjected in formalin test, it evoked a marked antinociceptive effect in both phases in a dose-dependent manner. The maximum (p < 0.01) pain-inhibiting effects were 61.36% and 65.89% in 1st and 2nd phases at 10 mg/kg i.p., respectively. Administration of atropine (non-selective cholinergic receptor antagonist) significantly (p < 0.05) antagonized the antihyperalgesic effect of the compound, while glibenclamide and naloxone did not alter the induced antinociceptive effect and thus, antinociceptive activity of the compound is mediated, at least in part, through cholinergic system antagonism; independent of calcium channel and opioidergic receptor participation. Furthermore, docking studies underlined strong COX-2 inhibitory activity of the compound. RESULT: Our data concluded that overall analgesic activity of the compound seems to involve COX-2 inhibition and activation of cholinergic receptors. However, further detailed studies are required in this direction to confirm the analgesic effect of the compound for its possible clinical utility. PMID- 27558684 TI - 2016 Awards in the Journal of Plant Research. PMID- 27558685 TI - Pseudouridylation of 7SK snRNA promotes 7SK snRNP formation to suppress HIV-1 transcription and escape from latency. AB - The 7SK snRNA sequesters P-TEFb, a general transcription elongation factor and human co-factor for HIV-1 Tat protein, into the catalytically inactive 7SK snRNP Little is known about how 7SK RNA is regulated to perform this function. Here, we show that most of 7SK is pseudouridylated at position U250 by the predominant cellular pseudouridine synthase machinery, the DKC1-box H/ACA RNP Pseudouridylation is critical to stabilize 7SK snRNP, as its abolishment by either mutation at or around U250 or depletion of DKC1, the catalytic component of the box H/ACA RNP, disrupts 7SK snRNP and releases P-TEFb to form the super elongation complex (SEC) and the Brd4-P-TEFb complex. The SEC is then recruited by Tat to the HIV-1 promoter to stimulate viral transcription and escape from latency. Thus, although 7SK RNA levels remain mostly unchanged, its function is modulated by pseudouridylation, which in turn controls transcription of both HIV 1 and cellular genes. PMID- 27558687 TI - Chapter 1 - Epidemiology, Aetiology and Symptomatology. PMID- 27558686 TI - Evaluation of a pediatric fluoroscopy training module to improve performance of upper gastrointestinal procedures in neonates with bilious emesis. AB - BACKGROUND: Life-threatening midgut volvulus usually occurs in infants with malrotation and requires rapid diagnosis and surgical treatment to prevent bowel necrosis and death. However, because of the low frequency of upper gastrointestinal studies performed in infants younger than 1 month, many diagnostic radiology residents finish their residency training having limited or no opportunity to perform or observe an upper gastrointestinal (GI) series for evaluation of bilious emesis in a neonate. OBJECTIVE: To determine whether adding simulated upper GI series on neonates with bilious emesis to the curriculum improves residents' skill and accuracy in diagnosing midgut volvulus. MATERIALS AND METHODS: We assessed the performance of 12 residents in training whose curriculum included simulated upper GI series (study group) and 10 traditionally trained residents (control group) using a multiple-choice test, checklist procedure evaluation and diagnostic accuracy scores for 3 randomly selected simulated upper GI series. We then compared the results from the study group that had simulation curriculum to the scores for the control group using the Mann Whitney test. We also analyzed the scores for the study group obtained prior to and after simulation curriculum using Wilcoxon signed rank test. RESULTS: There was a significant difference in test scores (study group median = 84.5%, control group median = 67.2%, P=0.001), overall diagnostic accuracy (study group median = 100%, control group median = 50%, P=0.011) and checklist evaluation (study group median = 83.3%, control group median = 70.8%, P=0.025) for the residents in the study group who completed simulation curriculum compared with the control group. There was also a significant difference in multiple-choice test scores for the study group before and after completion of simulation curriculum (before simulation curriculum median = 56.9%, after simulation curriculum median = 84.5%, P=0.002), checklist evaluation (before simulation curriculum median = 58.3%, after simulation curriculum median = 83.3%, P=0.002) and overall diagnostic accuracy scores (before simulation curriculum median = 50%, after simulation curriculum median = 100%, P=0.024). CONCLUSION: Radiology residents had significantly higher scores on a multiple-choice test, checklist procedure evaluation and overall diagnostic accuracy after completing a structured pediatric fluoroscopy curriculum that included simulated neonatal upper GI series and when compared to a control group of traditionally trained residents. PMID- 27558688 TI - [Purkinje images in slit lamp videography : Video article]. AB - Reflexes that accompany every examination with the slit lamp are usually regarded as annoying and therefore do not receive much attention. In the video available online, clinical information "hidden" in the Purkinje images is analyzed according to our concept of slit lamp videography. In the first part of the video, the four Purkinje images which are reflections on the eye's optical surfaces are introduced for the phakic eye. In the pseudophakic eye, however, the refracting surfaces of the intraocular lens (IOL) have excellent optical properties and therefore form Purkinje images 3 and 4 of high quality. Especially the third Purkinje image from the anterior IOL surface, which is usually hardly visible in the phakic eye can be detected deep in the vitreous, enlarged through the eye's own optics like a magnifying glass. Its area of reflection can be used to visualize changes of the anterior segment at high contrast. The third Purkinje image carries valuable information about the anterior curvature and, thus, about the power of the IOL. If the same IOL type is implanted in a patient, often a difference between right and left of 0.5 diopter in its power can be detected by the difference in size of the respective third Purkinje image. In a historical excursion to the "prenatal phase" of the slit lamp in Uppsala, we show that our most important instrument in clinical work was originally designed for catoptric investigations (of specular reflections). Accordingly A. Gullstrand called it an ophthalmometric Nernst lamp. PMID- 27558689 TI - [Good outcome in Acanthamoeba keratitis]. AB - A 31-year-old woman presented with mild keratitis of her left eye. The use of daily disposable contact lenses, regularly rinsed with tap water, and the development of perineural corneal infiltrates resulted in the clinical suspicion of infection with Acanthamoeba. Corneal epithelial scraping probe for polymerase chain reaction on Acanthamoeba confirmed the clinical diagnosis. Although the treatment was limited to low-dose propamidine monotherapy because of reduced tolerability, the keratitis healed with almost no scarring after 13 months of consequent medication. PMID- 27558690 TI - The impact of positron emission tomography on primary tumour delineation and dosimetric outcome in intensity modulated radiotherapy of early T-stage nasopharyngeal carcinoma. AB - BACKGROUND: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC), accurate delineation of the gross tumour volume (GTV) is important. Image registration of CT and MRI has been routinely used in treatment planning. With recent development of positron emission tomography (PET), the aims of this study were to evaluate the impact of PET on GTV delineation and dosimetric outcome in IMRT of early stage NPC patients. METHODS: Twenty NPC patients with T1 or T2 disease treated by IMRT were recruited. For each patient, 2 sets of NP GTVs were delineated separately, in which one set was performed using CT and MRI registration only (GTVCM), while the other set was carried out using PET, CT and MRI information (GTVCMP). A 9-field IMRT plan was computed based on the target volumes generated from CT and MRI (PTVCM). To assess the geometric difference between the GTVCM and GTVCMP, GTV volumes and DICE similarity coefficient (DSC), which measured the geometrical similarity between the two GTVs, were recorded. To evaluate the dosimetric impact, the Dmax, Dmin, Dmean and D95 of PTVs were obtained from their dose volume histograms generated by the treatment planning system. RESULTS: The overall mean volume of GTVCMP was greater than GTVCM by 4.4 %, in which GTVCMP was slightly greater in the T1 group but lower in the T2 group. The mean DSC of the whole group was 0.79 +/- 0.05. Similar mean DSC values were also obtained from the T1 and T2 groups separately. The dosimetric parameters of PTVCM fulfilled the planning requirements. When applying this plan to the PTVCMP, the average Dmin (56.9 Gy) and D95 (68.6 Gy) of PTVCMP failed to meet the dose requirements and demonstrated significant differences from the PTVCM (p = 0.001 and 0.016 respectively), whereas the doses to GTVCMP did not show significant difference with the GTVCM. CONCLUSION: In IMRT of early stage NPC, PET was an important imaging modality in radiotherapy planning so as to avoid underdosing the PTV, although its effect on GTV delineation was not significant. It was recommended that PET images should be included in the treatment planning of NPC patients. PMID- 27558691 TI - Responses of the arcto-boreal krill species Thysanoessa inermis to variations in water temperature: coupling Hsp70 isoform expressions with metabolism. AB - Recent studies have indicated a metabolic temperature sensitivity in both the arcto-boreal krill species Thysanoessa inermis and Thysanoessa raschii that may determine these species' abundance and population persistence at lower latitudes (up to 40 degrees N). T. inermis currently dominates the krill community in the Barents Sea and in the high Arctic Kongsfjord. We aimed to increase the knowledge on the upper thermal limit found in the latter species by estimating the CT50 value (19.7 degrees C) (critical temperature at which 50 % of animals are reactive) and by linking metabolic rate measurements with molecular approaches. Optical oxygen sensors were used to measure respiration rates in steps of 2 degrees C (from 0 to 16 degrees C). To follow the temperature-mediated mechanisms of passive response, i.e., as a proxy for molecular stress, molecular chaperone heat shock protein 70 (Hsp70) sequences were extracted from a transcriptome assembly, and the gene expression kinetics were monitored during an acute temperature exposure to 6 or 10 degrees C with subsequent recovery at 4 degrees C. Our results showed upregulation of hsp70 genes, especially the structurally constitutive and mitochondrial isoforms. These findings confirmed the temperature sensitivity of T. inermis and showed that the thermal stress took place before reaching the upper temperature limit estimated by respirometry at 12 degrees C. This study provides a baseline for further investigations into the thermal tolerances of arcto-boreal Thysanoessa spp. and comparisons with other krill species under different climatic regimes, especially Antarctica. PMID- 27558692 TI - Automated Blood Sample Preparation Unit (ABSPU) for Portable Microfluidic Flow Cytometry. AB - Portable microfluidic diagnostic devices, including flow cytometers, are being developed for point-of-care settings, especially in conjunction with inexpensive imaging devices such as mobile phone cameras. However, two pervasive drawbacks of these have been the lack of automated sample preparation processes and cells settling out of sample suspensions, leading to inaccurate results. We report an automated blood sample preparation unit (ABSPU) to prevent blood samples from settling in a reservoir during loading of samples in flow cytometers. This apparatus automates the preanalytical steps of dilution and staining of blood cells prior to microfluidic loading. It employs an assembly with a miniature vibration motor to drive turbulence in a sample reservoir. To validate performance of this system, we present experimental evidence demonstrating prevention of blood cell settling, cell integrity, and staining of cells prior to flow cytometric analysis. This setup is further integrated with a microfluidic imaging flow cytometer to investigate cell count variability. With no need for prior sample preparation, a drop of whole blood can be directly introduced to the setup without premixing with buffers manually. Our results show that integration of this assembly with microfluidic analysis provides a competent automation tool for low-cost point-of-care blood-based diagnostics. PMID- 27558693 TI - The power of mental adaptation to genetic abnormality. PMID- 27558694 TI - Disruption of the carA gene in Pseudomonas syringae results in reduced fitness and alters motility. AB - BACKGROUND: Pseudomonas syringae infects diverse plant species and is widely used in the study of effector function and the molecular basis of disease. Although the relationship between bacterial metabolism, nutrient acquisition and virulence has attracted increasing attention in bacterial pathology, there is limited knowledge regarding these studies in Pseudomonas syringae. The aim of this study was to investigate the function of the carA gene and the small RNA P32, and characterize the regulation of these transcripts. RESULTS: Disruption of the carA gene (DeltacarA) which encodes the predicted small chain of carbamoylphosphate synthetase, resulted in arginine and pyrimidine auxotrophy in Pseudomonas syringae pv. tomato DC3000. Complementation with the wild type carA gene was able to restore growth to wild-type levels in minimal medium. Deletion of the small RNA P32, which resides immediately upstream of carA, did not result in arginine or pyrimidine auxotrophy. The expression of carA was influenced by the concentrations of both arginine and uracil in the medium. When tested for pathogenicity, DeltacarA showed reduced fitness in tomato as well as Arabidopsis when compared to the wild-type strain. In contrast, mutation of the region encoding P32 had minimal effect in planta. DeltacarA also exhibited reduced motility and increased biofilm formation, whereas disruption of P32 had no impact on motility or biofilm formation. CONCLUSIONS: Our data show that carA plays an important role in providing arginine and uracil for growth of the bacteria and also influences other factors that are potentially important for growth and survival during infection. Although we find that the small RNA P32 and carA are co-transcribed, P32 does not play a role in the phenotypes that carA is required for, such as motility, cell attachment, and virulence. Additionally, our data suggests that pyrimidines may be limited in the apoplastic space of the plant host tomato. PMID- 27558695 TI - Bifunctional recombinant cellulase-xylanase (rBhcell-xyl) from the polyextremophilic bacterium Bacillus halodurans TSLV1 and its utility in valorization of renewable agro-residues. AB - The thermostable bifunctional CMCase and xylanase encoding gene (rBhcell-xyl) from Bacillus halodurans TSLV1 has been expressed in Escherichia coli. The recombinant E. coli produced rBhcell-xyl (CMCase 2272 and 910 U L-1 xylanase). The rBhcell-xyl is a ~62-kDa monomeric protein with temperature and pH optima of 60 degrees C and 6.0 with T1/2 of 7.0 and 3.5 h at 80 degrees C for CMCase and xylanase, respectively. The apparent K m values (CMC and Birchwood xylan) are 3.8 and 3.2 mg mL-1. The catalytic efficiency (k cat/K m ) values of xylanase and CMCase are 657 and 171 mL mg-1 min-1, respectively. End-product analysis confirmed that rBhcell-xyl is a unique endo-acting enzyme with exoglucanase activity. The rBhcell-xyl is a GH5 family enzyme possessing single catalytic module and carbohydrate binding module. The action of rBhcell-xyl on corn cobs and wheat bran liberated reducing sugars, which can be fermented to bioethanol and fine biochemicals. PMID- 27558696 TI - Lipid composition of circulating multiple-modified low density lipoprotein. AB - Atherogenic modified low- density lipoprotein (LDL) induces pronounced accumulation of cholesterol and lipids in the arterial wall, while native LDL seems to lack such capability. Therefore, modified LDL appears to be a major causative agent in the pathogenesis of atherosclerosis. Possible modifications of LDL particles include changes in size and density, desialylation, oxidation and acquisition of negative charge. Total LDL isolated from pooled plasma of patients with coronary atherosclerosis, as well as from healthy subjects contains two distinct subfractions: normally sialylated LDL and desialylated LDL, which can be isolated by binding to a lectin affinity column. We called the desialylated LDL subfraction circulating modified LDL (cmLDL). In this study, we focused on lipid composition of LDL particles, analysing the total LDL preparation and two LDL subfractions: cmLDL and native LDL. The composition of LDL was studied using thin layer chromatography. We found that cmLDL subfraction had decreased levels of free and esterified cholesterol, triglycerides, phospholipids (except for lysophosphatidylcholine) and sphingomyelin in comparison to native LDL. On the other hand, levels of mono-, and diglycerides, lysophosphatidylcholine and free fatty acids were higher in cmLDL than in native LDL. Our study demonstrated that lipid composition of cmLDL from atherosclerotic patients was altered in comparison to healthy subjects. In particular, phospholipid content was decreased, and free fatty acids levels were increased in cmLDL. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression. PMID- 27558697 TI - Host range expansion is density dependent. AB - The realized host range of herbivores is expected to increase with herbivore population density. Theory also predicts that trait similarity and phylogenetic relatedness between native and exotic plants is expected to increase the susceptibility of introduced plants to feeding by native herbivores. Whether the ability of native herbivores to extend their host range to introduced species is density dependent is still unknown. We addressed this question by monitoring pine processionary moth (PPM, Thaumetopoea pityocampa) attacks during nine consecutive years on 41 pine species (8 native and 33 introduced) planted in an arboretum. The survey encompassed latent and outbreak periods. A total of 28 pine species were attacked by PPM. There was no difference in the probability of attack between native and introduced pine species. Host range increased and was more phylogenetically clustered during outbreak than latent periods. When population density increased, PPM expanded its diet breadth by attacking introduced pine species that were closely related to native hosts. This study demonstrates the density dependence of host range expansion in a common pine herbivore. Importantly, it supports the idea that the degree of phylogenetic proximity between host species can be a better predictor of attacks than the introduction status, which may help to predict the outcomes of new plant-herbivore interactions. PMID- 27558698 TI - Lizards fail to plastically adjust nesting behavior or thermal tolerance as needed to buffer populations from climate warming. AB - Although observations suggest the potential for phenotypic plasticity to allow adaptive responses to climate change, few experiments have assessed that potential. Modeling suggests that Sceloporus tristichus lizards will need increased nest depth, shade cover, or embryonic thermal tolerance to avoid reproductive failure resulting from climate change. To test for such plasticity, we experimentally examined how maternal temperatures affect nesting behavior and embryonic thermal sensitivity. The temperature regime that females experienced while gravid did not affect nesting behavior, but warmer temperatures at the time of nesting reduced nest depth. Additionally, embryos from heat-stressed mothers displayed increased sensitivity to high-temperature exposure. Simulations suggest that critically low temperatures, rather than high temperatures, historically limit development of our study population. Thus, the plasticity needed to buffer this population has not been under selection. Plasticity will likely fail to compensate for ongoing climate change when such change results in novel stressors. PMID- 27558699 TI - Understanding conservationists' perspectives on the new-conservation debate. AB - A vibrant debate about the future direction of biodiversity conservation centers on the merits of the so-called new conservation. Proponents of the new conservation advocate a series of positions on key conservation ideas, such as the importance of human-dominated landscapes and conservation's engagement with capitalism. These have been fiercely contested in a debate dominated by a few high-profile individuals, and so far there has been no empirical exploration of existing perspectives on these issues among a wider community of conservationists. We used Q methodology to examine empirically perspectives on the new conservation held by attendees at the 2015 International Congress for Conservation Biology (ICCB). Although we identified a consensus on several key issues, 3 distinct positions emerged: in favor of conservation to benefit people but opposed to links with capitalism and corporations, in favor of biocentric approaches but with less emphasis on wilderness protection than prominent opponents of new conservation, and in favor of the published new conservation perspective but with less emphasis on increasing human well-being as a goal of conservation. Our results revealed differences between the debate on the new conservation in the literature and views held within a wider, but still limited, conservation community and demonstrated the existence of at least one viewpoint (in favor of conservation to benefit people but opposed to links with capitalism and corporations) that is almost absent from the published debate. We hope the fuller understanding we present of the variety of views that exist but have not yet been heard, will improve the quality and tone of debates on the subject. PMID- 27558701 TI - Coumarin-Induced DNA Ligation, Rearrangement to DNA Interstrand Crosslinks, and Photorelease of Coumarin Moiety. AB - Coumarin moieties react with thymine and cytosine in DNA by photoinduced [2+2] cycloaddition, which allows quantitative DNA interstrand crosslink (ICL) formation. Here, we report the application of coumarin analogues for DNA photoligation and the rearrangement of coumarin-induced ligation to ICL products. Both DNA sequences and the linker units at position 4 of the coumarin moieties affected coumarin-induced DNA photoligation. A flexible linker unit favored DNA ICL formation but led to inefficient photoligation, whereas coumarins without linker units greatly increased DNA photoligation efficiency. DNA photoligation induced by the coumarin moiety was photoswitchable. Ligation products were formed between coumarin and dT or dC upon 350 nm irradiation but reverted to the original single-stranded oligodeoxyribonucleotides (ODNs) upon 254 nm irradiation. Rearrangement of ligated ODNs into ICL products occurred during the switchable (350 nm/254 nm) processes. Additionally, photoinduced cleavage of coumarin 3 occurred with dC-3 cycloadducts upon 254 nm irradiation, which was confirmed by mass spectrometry analysis. PMID- 27558700 TI - Vitamin D and its impact on maternal-fetal outcomes in pregnancy: A critical review. AB - The role of vitamin D beyond its classical function in calcium homeostasis has been of significant interest in recent years. There has been expanding research on the pleiotropic role of vitamin D in pregnancy and the implications of its deficiency on maternal-fetal outcomes. Several studies have associated low maternal vitamin D status to adverse outcomes in pregnancy, including preeclampsia, gestational diabetes, preterm births, low birth weight, and others. Several randomized controlled clinical trials of Vitamin D supplementation during pregnancy have also been conducted. Though some of the studies found improvement in pregnancy outcomes with vitamin D supplementation, others have not shown any association. In this article, we have critically reviewed the observational and interventional studies, published primarily within the past two years (January 2014 to February 2016) on the influence of vitamin D deficiency on pregnancy and the impact of its supplementation. The potential underlying mechanisms of vitamin D in regulating each of the outcomes have also been discussed. PMID- 27558703 TI - Predictive value of the DASH tool for predicting return to work of injured workers with musculoskeletal disorders of the upper extremity. AB - OBJECTIVES: To determine whether the Disabilities of the Arm, Shoulder, and Hand (DASH) tool added to the predictive ability of established prognostic factors, including patient demographic and clinical outcomes, to predict return to work (RTW) in injured workers with musculoskeletal (MSK) disorders of the upper extremity. METHODS: A retrospective cohort study using a population-based database from the Workers' Compensation Board of Alberta (WCB-Alberta) that focused on claimants with upper extremity injuries was used. Besides the DASH, potential predictors included demographic, occupational, clinical and health usage variables. Outcome was receipt of compensation benefits after 3 months. To identify RTW predictors, a purposeful logistic modelling strategy was used. A series of receiver operating curve analyses were performed to determine which model provided the best discriminative ability. RESULTS: The sample included 3036 claimants with upper extremity injuries. The final model for predicting RTW included the total DASH score in addition to other established predictors. The area under the curve for this model was 0.77, which is interpreted as fair discrimination. This model was statistically significantly different than the model of established predictors alone (p<0.001). When comparing the DASH total score versus DASH item 23, a non-significant difference was obtained between the models (p=0.34). CONCLUSIONS: The DASH tool together with other established predictors significantly helped predict RTW after 3 months in participants with upper extremity MSK disorders. An appealing result for clinicians and busy researchers is that DASH item 23 has equal predictive ability to the total DASH score. PMID- 27558702 TI - Characterization of nano-structural and nano-mechanical properties of osteoarthritic subchondral bone. AB - BACKGROUND: Although articular cartilage is the primary tissues affected by osteoarthritis (OA), the underlying subchondral bone also undergoes noticeable changes. Despite the growing body of research into the biophysical and mechanical properties of OA bone there are few studies that have analysed the structure of the subchondral sclerosis at the nanoscale. In this study, the composition and nano-structural changes of human osteoarthritis (OA) subchondral bone were investigated to better understand the site-specific changes. METHODS: OA bone samples were collected from patients undergoing total knee replacement surgery and graded according to disease severity (grade I: mild OA; grade IV: severe OA). Transmission electron microscopy (TEM), Electron Diffraction, and Elemental Analysis techniques were used to explore the cross-banding pattern, nature of mineral phase and orientation of the crystal lattice. Subchondral bone nano hydroxyapatite powders were prepared and characterised using high resolution transmission electron microscopy (HR-TEM) and fourier transform infrared spectroscopy (FTIR). Subchondal bone mechanical properties were investigated using a nano-indentation method. RESULTS: In grade I subchondral bone samples, a regular periodic fibril banding pattern was observed and the c-axis orientation of the apatite crystals was parallel to the long axis of the fibrils. By contrast, in grade IV OA bone samples, the bulk of fibrils formed a random and undulated arrangement accompanied by a circular oriented pattern of apatite crystals. Fibrils in grade IV bone showed non-hierarchical intra-fibrillar mineralization and higher calcium (Ca) to phosphorous (P) (Ca/P) ratios. Grade IV OA bone showed higher crystallinity of the mineral content, increased modulus and hardness compared with grade I OA bone. CONCLUSIONS: The findings from this study suggest that OA subchondral sclerotic bone has an altered mineralization process which results in nano-structural changes of apatite crystals that is likely to account for the compromised mechanical properties of OA subchondral bones. PMID- 27558704 TI - Prediction of prognosis for people off sick with upper extremity musculoskeletal disorders. PMID- 27558705 TI - Arterialized Venous Bone Flaps: An Experimental Investigation. AB - In arterialized venous flaps (AVFs) the venous network is used to revascularize the flap. While the feasibility of AVFs in soft tissues has been reported there is no study on osseous AVFs. In this study we aim to assess the flap survival of osseous AVFs in a pig model. Medial femoral condyle flaps were elevated in 18 pigs. Three groups were created: AVF (n = 6), conventional arterial flap (cAF, n = 6) and bone graft (BG, n = 6). The AVFs were created by anastomosis of genicular artery with one vena comitans while leaving one efferent vein for drainage. After 6 months the specimens were harvested. The histology and histomorphometry of of the bone in cAF and AVF was significantly superior to bone grafts with a higher bone volume in AVFs (p = 0.01). This study demonstrates that osseous free flaps may be supported and survive using the technique of arterialization of the venous network. The concept of AVFs in osseous flaps may be feasible for revascularization of free flaps with an inadequate artery but well developed veins. Further experimental and clinical studies are needed to assess the feasibility of clinical use of arterialized venous bone flaps. PMID- 27558707 TI - Chromosomal rearrangements in holocentric organisms lead to reproductive isolation by hybrid dysfunction: The correlation between karyotype rearrangements and germination rates in sedges. AB - PREMISE OF THE STUDY: Understanding the drivers of speciation is a central task of evolutionary biology. Chromosomal rearrangements are known to play an important role in species diversification, but the role of rearrangements of holocentric chromosomes-chromosomes without localized centromeres-is poorly understood. METHODS: We made numerous artificial crosses between Carex scoparia individuals of different diploid chromosome numbers and, for comparison, between individuals of the same chromosome number. We studied chromosome pairing and chromosomal rearrangements in the F1 individuals using light microscopy. We then estimated germination rates as a function of geographic distance, genetic distance, chromosome number differences in parents, and pairing irregularities in F1 individuals, using generalized least squares to fit alternative regression models. KEY RESULTS: The most informative predictors of germination rates in the F1 generation are chromosome number differences and minimum number of chromosome pairing irregularities in the F1 individuals. Genetic and geographic distances between parents are not significant predictors. CONCLUSIONS: Holocentric chromosomal rearrangements play an important role in postzygotic reproductive isolation in Carex through F1 hybrid inviability and sterility. Hybrid dysfunction seems to be a suitable model for chromosomal speciation when there are several chromosomal rearrangements between parents. However, we have not tested the hypothesis that genome rearrangements may also play an important role in suppressing recombination between cytogenetically divergent populations. PMID- 27558708 TI - Bilateral hypoplasia of the maxillary sinus: swelling of the nasal mucosa after periapical periodontitis. PMID- 27558711 TI - Biologists Wanted: New Fluorescence Fluctuation Tools for Cell Biology. PMID- 27558712 TI - Spatiotemporal Fluctuation Analysis: A Powerful Tool for the Future Nanoscopy of Molecular Processes. AB - The enormous wealth of information available today from optical microscopy measurements on living samples is often underexploited. We argue that spatiotemporal analysis of fluorescence fluctuations using multiple detection channels can enhance the performance of current nanoscopy methods and provide further insight into dynamic molecular processes of high biological relevance. PMID- 27558710 TI - Spatio-temporal determinants of mental health and well-being: advances in geographically-explicit ecological momentary assessment (GEMA). AB - PURPOSE: Overview of geographically explicit momentary assessment research, applied to the study of mental health and well-being, which allows for cross validation, extension, and enrichment of research on place and health. METHODS: Building on the historical foundations of both ecological momentary assessment and geographic momentary assessment research, this review explores their emerging synergy into a more generalized and powerful research framework. RESULTS: Geographically explicit momentary assessment methods are rapidly advancing across a number of complimentary literatures that intersect but have not yet converged. Key contributions from these areas reveal tremendous potential for transdisciplinary and translational science. CONCLUSIONS: Mobile communication devices are revolutionizing research on mental health and well-being by physically linking momentary experience sampling to objective measures of socio ecological context in time and place. Methodological standards are not well established and will be required for transdisciplinary collaboration and scientific inference moving forward. PMID- 27558713 TI - Flow-Enhanced Stability of Rolling Adhesion through E-Selectin. AB - Selectin-ligand interactions mediate tethering and rolling of circulating leukocytes on the vessel wall during inflammation. Extensive study has been devoted to elucidating the kinetic and mechanical constraints of receptor-ligand interaction-mediated leukocyte adhesion, yet many questions remain unanswered. Here, we describe our design of an inverted flow chamber to compare adhesions of HL-60 cells to E-selectin in the upright and inverted orientations. This new, to our knowledge, design allowed us to evaluate the effect of gravity and to investigate the mechanisms of flow-enhanced adhesion. Cell rolling in the two orientations was qualitatively similar, and the quantitative differences can be explained by the effect of gravity, which promotes free-flowing cells to tether and detached cells to reattach to the surface in the upright orientation but prevents such attachment from happening in the inverted orientation. We characterized rolling stability by the lifetime of rolling adhesion and detachment of rolling cells, which could be easily measured in the inverted orientation, but not in the upright orientation because of the reattachment of transiently detached cells. Unlike the transient tether lifetime of E-selectin ligand interaction, which exhibited triphasic slip-catch-slip bonds, the lifetime of rolling adhesion displayed a biphasic trend that first increased with the wall shear stress, reached a maximum at 0.4 dyn/cm(2), and then decreased gradually. We have developed a minimal mathematical model for the probability of rolling adhesion. Comparison of the theoretical predictions to data has provided model validation and allowed evaluation of the effective two-dimensional association on rate, kon, and the binding affinity, Ka, of the E-selectin-ligand interaction. kon increased with the wall shear stress from 0.1 to 0.7 dyn/cm(2). Ka first increased with the wall shear stress, reached a maximum at 0.4 dyn/cm(2), and then decreased gradually. Our results provide insights into how the interplay between flow-dependent on-rate and off-rate of E-selectin-ligand bonds determine flow-enhanced cell rolling stability. PMID- 27558714 TI - Molecular and Physicochemical Factors Governing Solubility of the HIV gp41 Ectodomain. AB - The HIV gp41 ectodomain (e-gp41) is an attractive target for the development of vaccines and drugs against HIV because of its crucial role in viral fusion to the host cell. However, because of the high insolubility of e-gp41, most biophysical and structural analyses have relied on the production of truncated versions removing the loop region of gp41 or the utilization of nonphysiological solubilizing conditions. The loop region of gp41 is also known as principal immunodominant domain (PID) because of its high immunogenicity, and it is essential for gp41-mediated HIV fusion. In this study we identify the aggregation prone regions of the amino acid sequence of the PID and engineer a highly soluble mutant that preserves the trimeric structure of the wild-type e-gp41 under physiological pH. Furthermore, using a reverse mutagenesis approach, we analyze the role of mutated amino acids upon the physicochemical factors that govern solubility of e-gp41. On this basis, we propose a molecular model for e-gp41 self association, which can guide the production of soluble e-gp41 mutants for future biophysical analyses and biotechnological applications. PMID- 27558715 TI - Modeling Functional Motions of Biological Systems by Customized Natural Moves. AB - Simulating the functional motions of biomolecular systems requires large computational resources. We introduce a computationally inexpensive protocol for the systematic testing of hypotheses regarding the dynamic behavior of proteins and nucleic acids. The protocol is based on natural move Monte Carlo, a highly efficient conformational sampling method with built-in customization capabilities that allows researchers to design and perform a large number of simulations to investigate functional motions in biological systems. We demonstrate the use of this protocol on both a protein and a DNA case study. Firstly, we investigate the plasticity of a class II major histocompatibility complex in the absence of a bound peptide. Secondly, we study the effects of the epigenetic mark 5 hydroxymethyl on cytosine on the structure of the Dickerson-Drew dodecamer. We show how our customized natural moves protocol can be used to investigate causal relationships of functional motions in biological systems. PMID- 27558716 TI - Nanosecond Dynamics of Galphai1 Bound to Nucleotides or Ric-8A, a Galpha Chaperone with GEF Activity. AB - Resistance to Inhibitors of Cholinesterase A (Ric-8A) is a 60-kDa cytosolic protein that has chaperone and guanine nucleotide exchange (GEF) activity toward heterotrimeric G protein alpha subunits of the i, q, and 12/13 classes, catalyzing the release of GDP from Galpha and subsequent binding of GTP. In the absence of GTP or GTP analogs, and subsequent to GDP release, Galpha forms a stable nucleotide-free complex with Ric-8A. In this study, time-resolved fluorescence anisotropy measurements were employed to detect local motions of Galphai1 labeled at selected sites with Alexa 488 (C5) fluorescent dye (Ax) in the GDP, GTPgammaS (collectively, GXP), and Ric-8A-bound states. Sites selected for Alexa 488 (C5) derivatization were in the alpha-helical domain (residue 106), the alpha-helical domain-Ras-like domain hinge (residue 63), Switch I (residue 180), Switch II (residue 209), Switch III (residue 238), the alpha4 helix (residue 305), and at the junction between the purine-binding subsite in the beta6-alpha5 loop and the C-terminal alpha helix (residue 330). In the GXP-bound states, the Alexa fluorophore reports local motions with correlation times ranging from 1.0 to 1.8 ns. The dynamics at Ax180 is slower in Galphai1*GDP than in Galphai1*GTPgammaS. The reverse is true at Ax209. The order parameters, S(2), for Alexa probes at switch residues are high (0.78-0.88) in Galphai1*GDP and lower (0.67-0.75) in Galphai1*GTPgammaS, although in crystal structures, switch segments are more ordered in the latter. Local motions at Ax63, Ax180, Ax209, and Ax330 are all markedly slower (2.3-2.8 ns) in Galphai1:Ric-8A than in Galphai1*GXP, and only modest (+/- 0.1) differences in S(2) are observed at most sites in Galphai1:Ric-8A relative to Galphai1*GXP. The slow dynamics suggests long-range correlated transitions within an ensemble of states and, particularly in the hinge and switch segments that make direct contact with Ric-8A. Induction of Galphai1 structural heterogeneity by Ric-8A provides a mechanism for nucleotide release. PMID- 27558717 TI - The Conformation of Interfacially Adsorbed Ranaspumin-2 Is an Arrested State on the Unfolding Pathway. AB - Ranaspumin-2 (Rsn-2) is a surfactant protein found in the foam nests of the tungara frog. Previous experimental work has led to a proposed model of adsorption that involves an unusual clam-shell-like unhinging of the protein at an interface. Interestingly, there is no concomitant denaturation of the secondary structural elements of Rsn-2 with the large-scale transformation of its tertiary structure. In this work we use both experiment and simulation to better understand the driving forces underpinning this unusual process. We develop a modified Go-model approach where we have included explicit representation of the side chains to realistically model the interaction between the secondary structure elements of the protein and the interface. Doing so allows for the study of the underlying energy landscape that governs the mechanism of Rsn-2 interfacial adsorption. Experimentally, we study targeted mutants of Rsn-2, using the Langmuir trough, pendant drop tensiometry, and circular dichroism, to demonstrate that the clam-shell model is correct. We find that Rsn-2 adsorption is in fact a two-step process: the hydrophobic N-terminal tail recruits the protein to the interface after which Rsn-2 undergoes an unfolding transition that maintains its secondary structure. Intriguingly, our simulations show that the conformation Rsn-2 adopts at an interface is an arrested state along the denaturation pathway. More generally, our computational model should prove a useful, and computationally efficient, tool in studying the dynamics and energetics of protein-interface interactions. PMID- 27558719 TI - Solvation Thermodynamics of Oligoglycine with Respect to Chain Length and Flexibility. AB - Oligoglycine is a backbone mimic for all proteins and is prevalent in the sequences of intrinsically disordered proteins. We have computed the absolute chemical potential of glycine oligomers at infinite dilution by simulation with the CHARMM36 and Amber ff12SB force fields. We performed a thermodynamic decomposition of the solvation free energy (DeltaG(sol)) of Gly2-5 into enthalpic (DeltaH(sol)) and entropic (DeltaS(sol)) components as well as their van der Waals and electrostatic contributions. Gly2-5 was either constrained to a rigid/extended conformation or allowed to be completely flexible during simulations to assess the effects of flexibility on these thermodynamic quantities. For both rigid and flexible oligoglycine models, the decrease in DeltaG(sol) with chain length is enthalpically driven with only weak entropic compensation. However, the apparent rates of decrease of DeltaG(sol), DeltaH(sol), DeltaS(sol), and their elec and vdw components differ for the rigid and flexible models. Thus, we find solvation entropy does not drive aggregation for this system and may not explain the collapse of long oligoglycines. Additionally, both force fields yield very similar thermodynamic scaling relationships with respect to chain length despite both force fields generating different conformational ensembles of various oligoglycine chains. PMID- 27558718 TI - Molecular Effects of Concentrated Solutes on Protein Hydration, Dynamics, and Electrostatics. AB - Most studies of protein structure and function are performed in dilute conditions, but proteins typically experience high solute concentrations in their physiological scenarios and biotechnological applications. High solute concentrations have well-known effects on coarse protein traits like stability, diffusion, and shape, but likely also perturb other traits through finer effects pertinent at the residue and atomic levels. Here, NMR and molecular dynamics investigations on ubiquitin disclose variable interactions with concentrated solutes that lead to localized perturbations of the protein's surface, hydration, electrostatics, and dynamics, all dependent on solute size and chemical properties. Most strikingly, small polar uncharged molecules are sticky on the protein surface, whereas charged small molecules are not, but the latter still perturb the internal protein electrostatics as they diffuse nearby. Meanwhile, interactions with macromolecular crowders are favored mainly through hydrophobic, but not through polar, surface patches. All the tested small solutes strongly slow down water exchange at the protein surface, whereas macromolecular crowders do not exert such strong perturbation. Finally, molecular dynamics simulations predict that unspecific interactions slow down microsecond- to millisecond timescale protein dynamics despite having only mild effects on pico- to nanosecond fluctuations as corroborated by NMR. We discuss our results in the light of recent advances in understanding proteins inside living cells, focusing on the physical chemistry of quinary structure and cellular organization, and we reinforce the idea that proteins should be studied in native-like media to achieve a faithful description of their function. PMID- 27558721 TI - Exploring the Dynamics of the TWIK-1 Channel. AB - Potassium channels in the two-pore domain family (K2P) have various structural attributes that differ from those of other K(+) channels, including a dimeric assembly constituted of nonidentical domains and an expansive extracellular cap. Crystallization of the prototypical K2P channel, TWIK-1, finally revealed the structure of these characteristics in atomic detail, allowing computational studies to be undertaken. In this study, we performed molecular-dynamics simulations for a cumulative time of ~1 MUs to discern the mechanism of ion transport throughout TWIK-1. We observed the free passage of ions beneath the extracellular cap and identified multiple high-occupancy sites in close proximity to charged residues on the protein surface. Despite the overall topological similarity of the x-ray structure of the selectivity filter to other K(+) channels, the structure diverges significantly in molecular-dynamics simulations as a consequence of nonconserved residues in both pore domains contributing to the selectivity filter (T118 and L228). The behavior of such residues has been linked to channel inactivation and the phenomenon of dynamic selectivity, where TWIK-1 displays robust Na(+) inward flux in response to subphysiological K(+) concentrations. PMID- 27558720 TI - Direct Observation of the Intrinsic Backbone Torsional Mobility of Disordered Proteins. AB - The fundamental backbone dynamics of unfolded proteins arising due to intrinsic phi-psi dihedral angle fluctuations dictate the course of protein folding, binding, assembly, and function. These internal fluctuations are also critical for protein misfolding associated with a range of human diseases. However, direct observation and unambiguous assignment of this inherent dynamics in chemically denatured proteins is extremely challenging due to various experimental limitations. To directly map the backbone torsional mobility in the phi-psi dihedral angle space, we used a model intrinsically disordered protein, namely, alpha-synuclein, that adopts an expanded state under native conditions. We took advantage of nonoccurrence of tryptophan in alpha-synuclein and created a number of single-tryptophan variants encompassing the entire polypeptide chain. We then utilized highly sensitive picosecond time-resolved fluorescence depolarization measurements that allowed us to discern the site-specific torsional relaxation at a low protein concentration under physiological conditions. For all the locations, the depolarization kinetics exhibited two well-separated rotational correlation-time components. The shorter, subnanosecond component arises due to the local mobility of the indole side chain, whereas the longer rotational correlation-time component (1.37 +/- 0.15 ns), independent of global tumbling, represents a characteristic timescale for short-range conformational exchange in the phi-psi dihedral space. This correlation time represents an intrinsic timescale for torsional relaxation and is independent of position, which is expected for an extended polypeptide chain having little or no propensity to form persistent structures. We were also able to capture this intrinsic timescale at the N-terminal unstructured domain of the prion protein. Our estimated timescale of the segmental mobility is similar to that of unfolded proteins studied by nuclear magnetic resonance in conjunction with molecular dynamics simulations. Our results have broader implications for a diverse range of functionally and pathologically important intrinsically disordered proteins and disordered regions. PMID- 27558722 TI - Illuminating Myocyte-Fibroblast Homotypic and Heterotypic Gap Junction Dynamics Using Dynamic Clamp. AB - Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however, the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa that slow propagation, cause zig-zag conduction paths, and decouple cardiomyocytes, resulting in a substrate for cardiac arrhythmia. An emerging mechanism suggests that fibroblasts promote arrhythmogenesis through direct electrical interactions with cardiomyocytes via gap junction (GJ) channels. In the heart, three major connexin (Cx) isoforms, Cx40, Cx43, and Cx45, form GJ channels in cell-type specific combinations. Because each Cx is characterized by a unique time- and transjunctional voltage-dependent profile, we investigated whether the electrophysiological contributions of fibroblasts would vary with the specific composition of the myocyte-fibroblast (M-F) GJ channel. Due to the challenges of systematically modifying Cxs in vitro, we coupled native cardiomyocytes with in silico fibroblast and GJ channel electrophysiology models using the dynamic-clamp technique. We found that there is a reduction in the early peak of the junctional current during the upstroke of the action potential (AP) due to GJ channel gating. However, effects on the cardiomyocyte AP morphology were similar regardless of the specific type of GJ channel (homotypic Cx43 and Cx45, and heterotypic Cx43/Cx45 and Cx45/Cx43). To illuminate effects at the tissue level, we performed multiscale simulations of M-F coupling. First, we developed a cell specific model of our dynamic-clamp experiments and investigated changes in the underlying membrane currents during M-F coupling. Second, we performed two dimensional tissue sheet simulations of cardiac fibrosis and incorporated GJ channels in a cell type-specific manner. We determined that although GJ channel gating reduces junctional current, it does not significantly alter conduction velocity during cardiac fibrosis relative to static GJ coupling. These findings shed more light on the complex electrophysiological interplay between cardiac fibroblasts and myocytes. PMID- 27558723 TI - Identification of Bifurcations from Observations of Noisy Biological Oscillators. AB - Hair bundles are biological oscillators that actively transduce mechanical stimuli into electrical signals in the auditory, vestibular, and lateral-line systems of vertebrates. A bundle's function can be explained in part by its operation near a particular type of bifurcation, a qualitative change in behavior. By operating near different varieties of bifurcation, the bundle responds best to disparate classes of stimuli. We show how to determine the identity of and proximity to distinct bifurcations despite the presence of substantial environmental noise. Using an improved mechanical-load clamp to coerce a hair bundle to traverse different bifurcations, we find that a bundle operates within at least two functional regimes. When coupled to a high-stiffness load, a bundle functions near a supercritical Hopf bifurcation, in which case it responds best to sinusoidal stimuli such as those detected by an auditory organ. When the load stiffness is low, a bundle instead resides close to a subcritical Hopf bifurcation and achieves a graded frequency response-a continuous change in the rate, but not the amplitude, of spiking in response to changes in the offset force-a behavior that is useful in a vestibular organ. The mechanical load in vivo might therefore control a hair bundle's responsiveness for effective operation in a particular receptor organ. Our results provide direct experimental evidence for the existence of distinct bifurcations associated with a noisy biological oscillator, and demonstrate a general strategy for bifurcation analysis based on observations of any noisy system. PMID- 27558724 TI - Investigating the Structure of Multicomponent Gel-Phase Lipid Bilayers. AB - Single- and multicomponent lipid bilayers of 1,2-dipalmitoyl-sn-glycero-3 phosphatidylcholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), isostearyl isostearate, and heptadecanoyl heptadecanoate in the gel phase are studied via molecular dynamics simulations. It is shown that the structural properties of multicomponent bilayers can deviate strongly from the structures of their single-component counterparts. Specifically, the lipid mixtures are shown to adopt a compact packing by offsetting the positioning depths at which different lipid species are located in the bilayer. This packing mechanism affects the area per lipid, the bilayer height, and the chain tilt angles and has important consequences for other bilayer properties, such as interfacial hydrogen bonding and bilayer permeability. In particular, the simulations suggest that bilayers containing isostearyl isostearate or heptadecanoyl heptadecanoate are less permeable than pure 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine or DSPC bilayers. Furthermore, hydrogen-bond analysis shows that the residence times of lipid-water hydrogen bonds depend strongly on the bilayer composition, with longer residence times for bilayers that have a higher DSPC content. The findings illustrate and explain the fundamental differences between the properties of single- and multicomponent bilayers. PMID- 27558725 TI - Construction of Nuclear Envelope Shape by a High-Genus Vesicle with Pore-Size Constraint. AB - Nuclear pores have an approximately uniform distribution in the nuclear envelope of most living cells. Hence, the morphology of the nuclear envelope is a spherical stomatocyte with a high genus. We have investigated the morphology of high-genus vesicles under pore-size constraint using dynamically triangulated membrane simulations. Bending-energy minimization without volume or other constraints produces a circular-cage stomatocyte, where the pores are aligned in a circular line on an oblate bud. As the pore radius is reduced, the circular pore alignment is more stabilized than a random pore distribution on a spherical bud. However, we have clarified the conditions for the formation of a spherical stomatocyte: a small perinuclear volume, osmotic pressure within nucleoplasm, and repulsion between the pores. When area-difference elasticity is taken into account, the formation of cylindrical or budded tubules from the stomatocyte and discoidal stomatocyte is found. PMID- 27558726 TI - Kinetic Ductility and Force-Spike Resistance of Proteins from Single-Molecule Force Spectroscopy. AB - Ductile materials can absorb spikes in mechanical force, whereas brittle ones fail catastrophically. Here we develop a theory to quantify the kinetic ductility of single molecules from force spectroscopy experiments, relating force-spike resistance to the differential responses of the intact protein and the unfolding transition state to an applied mechanical force. We introduce a class of unistable one-dimensional potential surfaces that encompass previous models as special cases and continuously cover the entire range from ductile to brittle. Compact analytic expressions for force-dependent rates and rupture-force distributions allow us to analyze force-clamp and force-ramp pulling experiments. We find that the force-transmitting protein domains of filamin and titin are kinetically ductile when pulled from their two termini, making them resistant to force spikes. For the mechanostable muscle protein titin, a highly ductile model reconciles data over 10 orders of magnitude in force loading rate from experiment and simulation. PMID- 27558727 TI - Diffusion Tensor Analysis by Two-Dimensional Pair Correlation of Fluorescence Fluctuations in Cells. AB - In a living cell, the movement of biomolecules is highly regulated by the cellular organization into subcompartments that impose barriers to diffusion, can locally break the spatial isotropy, and ultimately guide these molecules to their targets. Despite the pivotal role of these processes, experimental tools to fully probe the complex connectivity (and accessibility) of the cell interior with adequate spatiotemporal resolution are still lacking. Here, we show how the heterogeneity of molecular dynamics and the location of barriers to molecular motion can be mapped in live cells by exploiting a two-dimensional (2D) extension of the pair correlation function (pCF) analysis. Starting from a time series of images collected for the same field of view, the resulting 2D pCF is calculated in the proximity of each point for each time delay and allows us to probe the spatial distribution of the molecules that started from a given pixel. This 2D pCF yields an accurate description of the preferential diffusive routes. Furthermore, we combine this analysis with the image-derived mean-square displacement approach and gain information on the average nanoscopic molecular displacements in different directions. Through these quantities, we build a fluorescence-fluctuation-based diffusion tensor that contains information on speed and directionality of the local dynamical processes. Contrary to classical fluorescence correlation spectroscopy and related methods, this combined approach can distinguish between isotropic and anisotropic local diffusion. We argue that the measurement of this iMSD tensor will contribute to advance our understanding of the role played by the intracellular environment in the regulation of molecular diffusion at the nanoscale. PMID- 27558728 TI - Stochastic Subcellular Organization of Dense-Core Vesicles Revealed by Point Pattern Analysis. AB - Dense-core vesicles (DCVs) are regulated secretory organelles found in many types of neurons. In neurons of the hippocampus, their cargo includes proteins that mediate several pivotal processes, including differentiation and synaptic plasticity. Motivated by interest in DCV distribution and its impact on cargo action, we have used fluorescence microscopy and statistical analysis to develop a quantitative model of the subcellular organization of DCVs in hippocampal neurons that are spontaneously active (their most prevalent state). We also have tested the functionally motivated hypothesis that these organelles are synaptically enriched. Variance-to-mean ratio, frequency distribution, and Moran's autocorrelation analyses reveal that DCV distribution along shafts, and within synapses, follows Poisson statistics, establishing that stochastically dictated organization sustains cargo function. Occupancy in boutons exceeds that at nearby extrasynaptic axonal sites by approximately threefold, revealing significant local presynaptic enrichment. Widespread stochastic organization is consistent with the emerging functional importance of synaptically and extrasynaptically localized DCVs. Presynaptic enrichment is consistent with the established importance of protecting presynaptic sites from depletion of DCV cargo. These results enhance understanding of the link between DCV organization and mechanisms of cargo action, and they reinforce the emerging theme that randomness is a prevalent aspect of synaptic organization and composition. PMID- 27558729 TI - Mechanically Induced Chromatin Condensation Requires Cellular Contractility in Mesenchymal Stem Cells. AB - Mechanical cues play important roles in directing the lineage commitment of mesenchymal stem cells (MSCs). In this study, we explored the molecular mechanisms by which dynamic tensile loading (DL) regulates chromatin organization in this cell type. Our previous findings indicated that the application of DL elicited a rapid increase in chromatin condensation through purinergic signaling mediated by ATP. Here, we show that the rate and degree of condensation depends on the frequency and duration of mechanical loading, and that ATP release requires actomyosin-based cellular contractility. Increases in baseline cellular contractility via the addition of an activator of G-protein coupled receptors (lysophosphatidic acid) induced rapid ATP release, resulting in chromatin condensation independent of loading. Conversely, inhibition of contractility through pretreatment with either a RhoA/Rock inhibitor (Y27632) or MLCK inhibitor (ML7) abrogated ATP release in response to DL, blocking load-induced chromatin condensation. With loading, ATP release occurred very rapidly (within the first 10-20 s), whereas changes in chromatin occurred at a later time point (~10 min), suggesting a downstream biochemical pathway mediating this process. When cells were pretreated with blockers of the transforming growth factor (TGF) superfamily, purinergic signaling in response to DL was also eliminated. Further analysis showed that this pretreatment decreased contractility, implicating activity in the TGF pathway in the establishment of the baseline contractile state of MSCs (in the absence of exogenous ligands). These data indicate that chromatin condensation in response to DL is regulated through the interplay between purinergic and RhoA/Rock signaling, and that ligandless activity in the TGF/bone morphogenetic proteins signaling pathway contributes to the establishment of baseline contractility in MSCs. PMID- 27558730 TI - Cellular Viscosity in Prokaryotes and Thermal Stability of Low Molecular Weight Biomolecules. AB - Some low molecular weight biomolecules, i.e., NAD(P)H, are unstable at high temperatures. The use of these biomolecules by thermophilic microorganisms has been scarcely analyzed. Herein, NADH stability has been studied at different temperatures and viscosities. NADH decay increased at increasing temperatures. At increasing viscosities, NADH decay rates decreased. Thus, maintaining relatively high cellular viscosity in cells could result in increased stability of low molecular weight biomolecules (i.e., NADH) at high temperatures, unlike what was previously deduced from studies in diluted water solutions. Cellular viscosity was determined using a fluorescent molecular rotor in various prokaryotes covering the range from 10 to 100 degrees C. Some mesophiles showed the capability of changing cellular viscosity depending on growth temperature. Thermophiles and extreme thermophiles presented a relatively high cellular viscosity, suggesting this strategy as a reasonable mechanism to thrive under these high temperatures. Results substantiate the capability of thermophiles and extreme thermophiles (growth range 50-80 degrees C) to stabilize and use generally considered unstable, universal low molecular weight biomolecules. In addition, this study represents a first report, to our knowledge, on cellular viscosity measurements in prokaryotes and it shows the dependency of prokaryotic cellular viscosity on species and growth temperature. PMID- 27558731 TI - Costs of Clock-Environment Misalignment in Individual Cyanobacterial Cells. AB - Circadian rhythms are endogenously generated daily oscillations in physiology that are found in all kingdoms of life. Experimental studies have shown that the fitness of Synechococcus elongatus, a photosynthetic microorganism, is severely affected in non-24-h environments. However, it has been difficult to study the effects of clock-environment mismatch on cellular physiology because such measurements require a precise determination of both clock state and growth rate in the same cell. Here, we designed a microscopy platform that allows us to expose cyanobacterial cells to pulses of light and dark while quantitatively measuring their growth, division rate, and circadian clock state over many days. Our measurements reveal that decreased fitness can result from a catastrophic growth arrest caused by unexpected darkness in a small subset of cells with incorrect clock times corresponding to the subjective morning. We find that the clock generates rhythms in the instantaneous growth rate of the cell, and that the time of darkness vulnerability coincides with the time of most rapid growth. Thus, the clock mediates a fundamental trade-off between growth and starvation tolerance in cycling environments. By measuring the response of the circadian rhythm to dark pulses of varying lengths, we constrain a mathematical model of a population's fitness under arbitrary light/dark schedules. This model predicts that the circadian clock is only advantageous in highly regular cycling environments with frequencies sufficiently close to the natural frequency of the clock. PMID- 27558732 TI - Ceftriaxone pretreatment reduces the propensity of postpartum depression following stroke during pregnancy in rats. AB - OBJECTIVE: Ischemic stroke increases the propensity to develop depression in humans and laboratory animals, and we hypothesized that such an incidence during pregnancy may increase the risk for the development of postpartum depression (PPD). MATERIALS AND METHODS: To test this hypothesis, we used bilateral common carotid arteries occlusion (BCCAO) to induce transient cerebral ischemia in pregnant rats, and evaluated its effects on subsequent development of PPD in dams. Additionally, we investigated whether ceftriaxone pretreatments before the induction of brain ischemia could alter the propensity of PPD. RESULTS: We found that 15min BCCAO during pregnancy enhanced immobility time and reduced the frequency of swimming or climbing behaviors in the forced swim test, and decreased the sucrose preference in dams at postpartum day 21. Such behavioral alterations were associated with lower level of GLT-1 expression in the medial prefrontal cortical regions (mPFC) of PPD dams. Specifically, mPFC GLT-1 expression levels in dams with ischemia history were correlated with sucrose preference levels at postpartum day 21. Finally, ceftriaxone pretreatment (200mg/kg/day, 5days) before the 15min BCCAO prevented the development of PPD, and prevented the reduction of GLT-1 expression in the mPFC. CONCLUSIONS: Taken together, our results suggested that ceftriaxone pretreatment before brain ischemia during pregnancy may reduce the propensity for the development of PPD by preventing the loss of GLT-1 expression in the mPFC. PMID- 27558733 TI - Effects of Lipid Structure Changed by Interesterification on Melting Property and Lipemia. AB - Interesterification or the randomization reaction changes fatty acid positional distribution and solid fat content of fats, which may consequently affect fat absorption and metabolism. It is well established that saturated fatty acids in the sn-2 position of triacylglycerols (TAG) have better digestibility and lower postprandial chylomicron clearance compared to those in the sn-1,3 positions in animal experiments. TAG structure is also shown to affect fasting lipid level and atherosclerosis in animals, but fat interesterification it has been shown to not affect fasting lipid level in human adults. However, its effect on postprandial responses is controversial. In this review, the complex results of studies of interesterification and lipemia were briefly discussed. More importantly, the confounding of two factors that are both changed by interesterification, TAG structure and solid fat content as the main limitation on understanding how interesterification affects lipemia is emphasized. Separation of the two factors is possible using paired fats as demonstrated. This paper also discusses some intriguing effects of fats having saturated fatty acids in the sn-2 position and the need for future research. PMID- 27558734 TI - A brief clinical case of monitoring of oxygenator performance and patient-machine interdependency during prolonged veno-venous extracorporeal membrane oxygenation. AB - Monitoring veno-venous extracorporeal membrane oxygenation (vvECMO) during 76 days of continuous support in a 42-years old patient with end-stage pulmonary disease, listed for double-lung transplantation. Applying a new monitor (Landing(r), Eurosets, Medolla, Italy) and describing how measured and calculated parameters can be used to understand the variable interdependency between artificial membrane lung (ML) and patient native lung (NL). During vvECMO, in order to understand how the respiratory function is shared between ML and NL, ideally we should obtain data about oxygen transfer and CO2 removal, both by ML and NL. Measurements for NL can be made on the mechanical ventilator. Measurements for ML are typically made from gas analysis on blood samples drawn from the ECMO system before and after the oxygenator, and therefore are non continuous. Differently, the Landing monitor provides a continuous measurement of the oxygen transfer from the ML, combined with hemoglobin level, saturation of drained blood and saturation of reinfused blood. Moreover, the Landing monitor provides hemodynamics data about circulation through the ECMO system, with blood flow, pre-oxygenator pressure and post-oxygenator pressure. Of note, measurements include the drain negative pressure, whose monitoring may be particularly useful to prevent hemolysis. Real-time monitoring of vvECMO provides data helpful to understand the complex picture of a patient with severely damaged lungs on one side and an artificial lung on the other side. Data from vvECMO monitoring may help to adapt the settings of both mechanical ventilator and vvECMO. Data about oxygen transfer by the oxygenator are important to evaluate the performance of the device and may help to avoid unnecessary replacements, thus reducing risks and costs. PMID- 27558736 TI - Spatial and temporal distributions of polycyclic aromatic hydrocarbons in the Northern Arabian Gulf sediments. AB - Surficial sediment samples were collected from 25 locations within Kuwait Bay and outside the Bay, in the Northwestern Arabian Gulf, to access recent polycyclic aromatic hydrocarbon pollution in Kuwait. Time trends in the depositional history of PAHs to this portion of the Arabian Gulf was reconstructed from the analysis of a dated sediment core. Intersite differences in concentration exist although these differences were not statistically significant (p=0.08). However, organic carbon normalized concentrations within Kuwait Bay were 4 times higher than the average concentrations outside the Bay and were shown to be statistically significant (p<0.001). The sedimentary record showed that SigmaPAHs concentration fluctuated between 12 and 25ngg-1 before 1970. Concentrations then increased sharply to a maximum of 45ngg-1 around the late 1970s and early 1980s followed by an exponential decrease in concentration to pre-1970 "background" concentrations of between 12 and 25ngg-1. PMID- 27558735 TI - The Impact of Oxytocin Gene Knockout on Sexual Behavior and Gene Expression Related to Neuroendocrine Systems in the Brain of Female Mice. AB - Social relations are built and maintained from the interaction among individuals. The oxytocin (OT), vasopressin (VP), estrogen, dopamine, and their receptors are involved in the modulation of sexual behavior in females. This study aimed to analyze the impact of OT gene knockout (OTKO) on sexual behavior and the gene expression of oxytocin (OTR), estrogen alpha (ERalpha), estrogen beta (ERbeta), vasopressin (V1aR), and dopamine (D2R) receptors in the olfactory bulb (OB), prefrontal cortex (PFC), hippocampus (HPC), and hypothalamus (HPT), as well as in the synthesis of VP in the HPT of female mice. Wild-type (WT) littermates were used for comparisons. The CDNAs were synthesized by polymerase chain reaction and the gene expression was calculated with the 2-DeltaDeltaCt formula. Our results showed that the absence of OT caused an increase in the frequency and duration of non-receptive postures and a decrease in receptive postures in the OTKO. OTKO females showed a significant decrease in the gene expression of OTR in the HPC, V1aR in the HPT, and ERalpha and ERbeta in the PFC. There was no significant difference in the gene expression of D2R of OTKO. However, OTKO showed an increased gene expression of V1aR in the HPC. There is no significant difference in VP mRNA synthesis in the HPT between OTKO and WT. Our findings demonstrate that the absence of OT leads to significant changes in the expression of the studied genes (OTR, ERalpha, ERbeta, V1aR), and these changes may contribute to the decreased sexual behavior observed in OTKO females. PMID- 27558737 TI - Spatial variations in annual cycles of body-size spectra of planktonic ciliates and their environmental drivers in marine ecosystems. AB - Body-size spectra has proved to be a useful taxon-free resolution to summarize a community structure for bioassessment. The spatial variations in annual cycles of body-size spectra of planktonic ciliates and their environmental drivers were studied based on an annual dataset. Samples were biweekly collected at five stations in a bay of the Yellow Sea, northern China during a 1-year cycle. Based on a multivariate approach, the second-stage analysis, it was shown that the annual cycles of the body-size spectra were significantly different among five sampling stations. Correlation analysis demonstrated that the spatial variations in the body-size spectra were significantly related to changes of environmental conditions, especially dissolved nitrogen, alone or in combination with salinity and dissolve oxygen. Based on results, it is suggested that the nutrients may be the environmental drivers to shape the spatial variations in annual cycles of planktonic ciliates in terms of body-size spectra in marine ecosystems. PMID- 27558738 TI - White-faced storm-petrels Pelagodroma marina predated by gulls as biological monitors of plastic pollution in the pelagic subtropical Northeast Atlantic. AB - Marine plastic pollution is rapidly growing and is a source of major concern. Seabirds often ingest plastic debris and are increasingly used as biological monitors of plastic pollution. However, virtually no studies have assessed plastics in seabirds in the deep subtropical North Atlantic. We investigated whether remains of white-faced storm-petrels (WFSP) present in gull pellets could be used for biomonitoring. We analysed 263 pellets and 79.0% of these contained plastic debris originating in the digestive tract of WFSP. Pellets with no bird prey did not contain plastics. Most debris were fragments (83.6%) with fewer plastic pellets (8.2%). Light-coloured plastics predominated (71.0%) and the most frequent polymer was HDPE (73.0%). Stable isotopes in toe-nails of WFSP containing many versus no plastics did not differ, indicating no individual specialisation leading to differential plastic ingestion. We suggest WFSP in pellets are highly suitable to monitor the little known pelagic subtropical Northeast Atlantic. PMID- 27558739 TI - Suicide crisis among indigenous Australians tests rural services. PMID- 27558740 TI - Effectiveness of Web-Delivered Acceptance and Commitment Therapy in Relation to Mental Health and Well-Being: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The need for effective interventions to improve mental health and emotional well-being at a population level are gaining prominence both in the United Kingdom and globally. Advances in technology and widespread adoption of Internet capable devices have facilitated rapid development of Web-delivered psychological therapies. Interventions designed to manage a range of affective disorders by applying diverse therapeutic approaches are widely available. OBJECTIVE: The main aim of this review was to evaluate the evidence base of acceptance and commitment therapy (ACT) in a Web-based delivery format. METHOD: A systematic review of the literature and meta-analysis was conducted. Two electronic databases were searched for Web-delivered interventions utilizing ACT for the management of affective disorders or well-being. Only Randomized Controlled Trials (RCTs) were included. RESULTS: The search strategy identified 59 articles. Of these, 10 articles met the inclusion criteria specified. The range of conditions and outcome measures that were identified limited the ability to draw firm conclusions about the efficacy of Web-delivered ACT-based intervention for anxiety or well-being. CONCLUSIONS: ACT in a Web-based delivery format was found to be effective in the management of depression. Rates of adherence to study protocols and completion were high overall suggesting that this therapeutic approach is highly acceptable for patients and the general public. PMID- 27558741 TI - Frailty as a predictor of disabilities among community-dwelling older people: a systematic review and meta-analysis. AB - BACKGROUND: Frailty has been shown to be associated with disability in the previous studies. However, it is not clear how consistently or to how much degree frailty is actually associated with the future disability risks. METHODS: A systematic review of the literature was conducted using Embase, MEDLINE, CINAHL, PsycINFO, and the Cochrane Library for any prospective studies published from 2010 to September 2015 examining associations between baseline frailty status and subsequent risk of developing or worsening disabilities among community-dwelling older people. A meta-analysis was performed to synthesize pooled estimates. RESULTS: Of 7012 studies identified through the systematic review, 20 studies were included in the meta-analysis. Twelve studies examined activities of daily living (ADL) disability risks, two studies examined instrumental activities of daily living (IADL) disability risks, and six studies examined both ADL and IADL disability risks. Overall, frail older people were more likely to develop or worsen disabilities in ADL (12 studies, pooled OR = 2.76, 95% CI = 2.23-3.44, p < 0.00001; 5 studies, pooled HR = 2.23, 95% CI = 1.42-3.49, p < 0.00001) and IADL (6 studies, pooled OR = 3.62, 95% CI = 2.32-5.64, p < 0.00001; 2 studies, pooled HR = 4.24, 95% CI = 0.85-21.28, p = 0.08). Prefrailty was also associated with incident or worsening disability risks to a lesser degree in most pooled analyses. High heterogeneity observed among 12 studies with OR of ADL disability risks for frailty was explored using subgroup analyses, which suggested methodological quality and mean age of the cohort were the possible causes. CONCLUSION: This systematic review meta-analysis quantitatively showed that frail older people are at higher risks of disabilities. These results are important for all related parties given population aging worldwide. Interventions for frailty are important to prevent disability and preserve physical functions, autonomy, and quality of life. Implications for Rehabilitation Although frailty has been shown to be associated with disability and considered as a precursor of disability, it is not clear how consistently or to how much degree frailty is actually associated with the future disability risks. This systematic review and meta-analysis quantitatively shows frailty is a significant predictor of incident and worsening ADL and IADL disabilities. It is a pressing priority to develop interventions for frailty to prevent disability and preserve older people's physical functions, autonomy, and quality of life. PMID- 27558742 TI - Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window. AB - Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness - infectivity, spread and pathogenesis - is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field. PMID- 27558743 TI - Small secreted proteins enable biofilm development in the cyanobacterium Synechococcus elongatus. AB - Small proteins characterized by a double-glycine (GG) secretion motif, typical of secreted bacterial antibiotics, are encoded by the genomes of diverse cyanobacteria, but their functions have not been investigated to date. Using a biofilm-forming mutant of Synechococcus elongatus PCC 7942 and a mutational approach, we demonstrate the involvement of four small secreted proteins and their GG-secretion motifs in biofilm development. These proteins are denoted EbfG1-4 (enable biofilm formation with a GG-motif). Furthermore, the conserved cysteine of the peptidase domain of the Synpcc7942_1133 gene product (dubbed PteB for peptidase transporter essential for biofilm) is crucial for biofilm development and is required for efficient secretion of the GG-motif containing proteins. Transcriptional profiling of ebfG1-4 indicated elevated transcript levels in the biofilm-forming mutant compared to wild type (WT). However, these transcripts decreased, acutely but transiently, when the mutant was cultured in extracellular fluids from a WT culture, and biofilm formation was inhibited. We propose that WT cells secrete inhibitor(s) that suppress transcription of ebfG1 4, whereas secretion of the inhibitor(s) is impaired in the biofilm-forming mutant, leading to synthesis and secretion of EbfG1-4 and supporting the formation of biofilms. PMID- 27558744 TI - Laparoscopic partial splenectomy for giant cyst using a radiofrequency-assisted device: a case report. AB - BACKGROUND: Although radiofrequency-assisted devices have sometimes been used in partial splenectomy, this is not a common technique. This report describes the first case of laparoscopic partial splenectomy using an RF-assisted device (Coolinside) which allows both coagulation and transection of the parenchyma and eventually the protective coagulation of the remnant side. CASE PRESENTATION: A 27-year-old woman was found to have a giant hydatic cyst measuring 12.0 * 14.0 * 16.6 cm that mainly occupied the lower pole of the spleen and retroperitoneal space. The patient underwent a laparoscopic partial splenectomy using an RF-based device designed to accomplish both the coagulation and dissection of the splenic tissue. The estimated blood loss was less than 200 mL. CONCLUSIONS: Even though RF ablation has traditionally been used for hepatic parenchymal transection, it seems equally suited to partial splenectomy. This device seems to provide good results, minimizing blood loss during partial splenectomy; however, randomized trials will be necessary to see if the results are superior to those of other techniques. PMID- 27558746 TI - It's time to take psilocybin seriously as a possible treatment for substance use disorders. PMID- 27558747 TI - New developments in the effort to model ecosystems under water stress. PMID- 27558745 TI - Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. AB - BACKGROUND: The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. METHODS: Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. RESULTS: Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. CONCLUSIONS: Exposure to inhaled nicotine-containing e cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use. PMID- 27558748 TI - The geographic mosaic of plant chemistry and its effects on community and population genetic diversity. PMID- 27558749 TI - Did thermophilous trees spread into central Europe during the Late Glacial? PMID- 27558750 TI - Paleobotanical and climate data support the plausibility of temperate trees spread into central Europe during the Late Glacial. PMID- 27558751 TI - A multilayered regulatory mechanism for the autoinhibition and activation of a plant CC-NB-LRR resistance protein with an extra N-terminal domain. AB - The tomato resistance protein Sw-5b differs from the classical coiled-coil nucleotide-binding leucine-rich repeat (CC-NB-LRR) resistance proteins by having an extra N-terminal domain (NTD). To understand how NTD, CC and NB-LRR regulate autoinhibition and activation of Sw-5b, we dissected the function(s) of each domain. When viral elicitor was absent, Sw-5b LRR suppressed the central NB-ARC to maintain autoinhibition of the NB-LRR segment. The CC and NTD domains independently and additively enhanced the autoinhibition of NB-LRR. When viral elicitor was present, the NB-LRR segment of Sw-5b was specifically activated to trigger a hypersensitive response. Surprisingly, Sw-5b CC suppressed the activation of NB-LRR, whereas the extra NTD of Sw-5b became a positive regulator and fully activated the resistance protein, probably by relieving the inhibitory effects of the CC. In infection assays of transgenic plants, the NB-LRR segment alone was insufficient to confer resistance against Tomato spotted wilt tospovirus; the layers of NTD and CC regulation on NB-LRR were required for Sw-5b to confer resistance. Based on these findings, we propose that, to counter the negative regulation of the CC on NB-LRR, Sw-5b evolved an extra NTD to coordinate with the CC, thus developing a multilayered regulatory mechanism to control autoinhibition and activation. PMID- 27558752 TI - Endoplasmic reticulum-associated N-glycan degradation of cold-upregulated glycoproteins in response to chilling stress in Arabidopsis. AB - N-glycosylation has a great impact on glycoprotein structure, conformation, stability, solubility, immunogenicity and enzyme activity. Structural characterization of N-glycoproteome has been challenging but can provide insights into the extent of protein folding and surface topology. We describe a highly sensitive proteomics method for large-scale identification and quantification of glycoproteins in Arabidopsis through (15) N-metabolic labeling, selective enrichment of glycopeptides, data-dependent MS/MS analysis and automated database searching. In-house databases of Arabidopsis glycoproteins and glycopeptides containing Asn-X-Ser/Thr/Cys motifs were constructed by reducing 20% and 90% of the public database size, respectively, to enable a rapid analysis of large datasets for comprehensive identification and quantification of glycoproteins and heterogeneous N-glycans in a complex mixture. Proteome-wide analysis identified c. 100 stress-related N-glycoproteins, of which the endoplasmic reticulum (ER) resident proteins were examined to be up-regulated. Quantitative measurements provided a molecular signature specific to glycoproteins for determining the degree of plant stress at low temperature. Structural N-glycoproteomics following time-course cold treatments revealed the stress-responsive degradation of high mannose type N-glycans in ER in response to chilling stress, which may aid in elucidating the cellular mechanisms of protein relocation, transport, trafficking, misfolding and degradation under stress conditions. PMID- 27558754 TI - How human IgGs against DNA recognize oligonucleotides and DNA. AB - In the literature, there are no available data on how anti-DNA antibodies recognize DNA. In the present work, to study the molecular mechanism of DNA recognition by antibodies, we have used anti-DNA IgGs from blood sera of patients with multiple sclerosis. A stepwise increase in ligand complexity approach was used to estimate the relative contributions of virtually every nucleotide unit of different single- (ss) and double-stranded (ds) oligonucleotides to their affinity for IgG fraction having high affinity to DNA-cellulose. DNA-binding site disposed on the heavy chain demonstrates higher affinity to different dNMPs (Kd = 0.63MUM-3.8MUM) than the site located on the light chain (28MUM-170MUM). The heavy and light chains interact independently forming relatively strong contacts with 2 to 4 nucleotides of short homo- and hetero-d(pN)2-9 . Then the increase in the affinity of different d(pN)n became minimal, and at n >= 8 to 9, all dependencies reached plateaus: approximately 3.2nM to 20nM and approximately 200nM to 460nM for the heavy and light chains, respectively. A similar situation was observed for different ribooligonucleotides, in which their affinity is 6 fold to 100-fold lower than that for d(pN)n . Transition from ss to ds d(pN)n leads to a moderate increase in affinity of ligands to DNA-binding site of heavy chains, while light chains demonstrate the same affinity for ss and ds d(pN)n . Long supercoiled DNA interacts with both heavy and light chains with affinity of approximately 10-fold higher than that for short oligonucleotides. The thermodynamic models were constructed to describe the interactions of IgGs light and heavy chains with DNA. PMID- 27558753 TI - A Quantitative Characterization of Nucleoplasmin/Histone Complexes Reveals Chaperone Versatility. AB - Nucleoplasmin (NP) is an abundant histone chaperone in vertebrate oocytes and embryos involved in storing and releasing maternal histones to establish and maintain the zygotic epigenome. NP has been considered a H2A-H2B histone chaperone, and recently it has been shown that it can also interact with H3-H4. However, its interaction with different types of histones has not been quantitatively studied so far. We show here that NP binds H2A-H2B, H3-H4 and linker histones with Kd values in the subnanomolar range, forming different complexes. Post-translational modifications of NP regulate exposure of the polyGlu tract at the disordered distal face of the protein and induce an increase in chaperone affinity for all histones. The relative affinity of NP for H2A-H2B and linker histones and the fact that they interact with the distal face of the chaperone could explain their competition for chaperone binding, a relevant process in NP-mediated sperm chromatin remodelling during fertilization. Our data show that NP binds H3-H4 tetramers in a nucleosomal conformation and dimers, transferring them to DNA to form disomes and tetrasomes. This finding might be relevant to elucidate the role of NP in chromatin disassembly and assembly during replication and transcription. PMID- 27558755 TI - Factors Influencing Diaphragmatic Compound Motor Action Potentials During Cryoballoon Ablation for Atrial Fibrillation. AB - INTRODUCTION: The diaphragmatic compound motor action potentials (CMAPs) have been used to predict and prevent phrenic nerve injury (PNI) during cryoballoon ablation of right pulmonary veins. We sought to assess factors that influence the amplitude of the surface CMAP recordings. METHODS AND RESULTS: We analyzed CMAPs from consecutive patients undergoing cryoballoon ablation for paroxysmal atrial fibrillation. CMAP recordings were obtained using electrocardiography electrodes positioned in the "modified lead I" method while stimulating the right PN, until loss of capture (ascertained by palpation and fluoroscopy of the right hemi diaphragm). A total of 55 patients (age 63 +/- 11 years; 60% men; body mass index [BMI] 31 +/- 6) had adequate CMAP recordings and were included for evaluation of CMAP signals. CMAPs demonstrated 2 distinct components, an early higher amplitude signal (pacing artifact) and a later lower amplitude signal (true diaphragmatic CMAP). There was no significant change in the true CMAP recording amplitude with decrease in stimulus strength (P = 0.1). There was no impact of BMI on CMAP amplitude (P = 0.93). There was a significant phasic respiratory variation in CMAP amplitude with a mean decrease in CMAP amplitude of 10.8% (range: 8-12%) with inspiration lasting an average of 2 beats (P < 0.001). A decrease in CMAP amplitude of >30% was noted in 6 cases (11%) and termination of cryoablation prevented PNI. CONCLUSION: Diaphragmatic CMAP amplitude is not affected by stimulus strength or BMI. There is a significant respirophasic decrease in CMAP signal amplitude with inspiration. It is important to be aware of this variation to avoid premature termination of cryoablation. PMID- 27558756 TI - Pulmonary thromboembolism during pregnancy in a woman with beta-thalassaemia who had undergone splenectomy. PMID- 27558757 TI - Defining metabolic syndrome and factors associated with metabolic syndrome in a poly-pharmaceutical population. AB - OBJECTIVES: Metabolic Syndrome (METs) definitions vary and diagnosis takes into account consumption of medications commonly prescribed for conditions defining METs. This paper evaluates the potential differences in population characteristics using two different methods of defining METs, with and without the adjustment of the effects of pharmacotherapy on biochemical and blood pressure (BP) measurements Methods: This was a cross-sectional study utilizing the Malaysian Elders Longitudinal Research (MELoR) cohort comprising urban community-dwellers aged >=55 years. Participants were interviewed using a structured questionnaire during home visits where medications were reviewed. Health impacts assessed included heart disease, stroke, body mass index (BMI), peptic ulcers, arthritis, and number of medications and comorbidities. Risk factors and health impacts associated with METs were determined by Poisson multivariate regression models using a binary and count dependent variables. RESULTS: A total of 891 participants with a mean (SD) age of 68.6 (7.3) years were included. The prevalence of METs vary from 52.7% to 35.1% depending upon the definition used. The risk factors associated with METs were increasing age, ethnicity, lower education levels, BMI, stroke and medication use. Male gender was considered a risk factor following modification for medication usage using a count model. The drug-modified model removed marginal candidates prescribed medications used for specific conditions which defined METs who did not meet the criteria once their BP or biochemical parameters were modified for the effects of medication-use. CONCLUSION: The IDF definition for METs that makes allowance for treatment for each specific condition can lead to an overestimation in the prevalence of METs in population studies. Not including those medicated with normal results conversely underestimates the prevalence of METs. We have therefore proposed adjustments to BP and lipid measurements based on pooled mean effects from published systematic reviews to mitigate bias in future research on prevalence of METs. PMID- 27558758 TI - Disordered actomyosin networks are sufficient to produce cooperative and telescopic contractility. AB - While the molecular interactions between individual myosin motors and F-actin are well established, the relationship between F-actin organization and actomyosin forces remains poorly understood. Here we explore the accumulation of myosin induced stresses within a two-dimensional biomimetic model of the disordered actomyosin cytoskeleton, where myosin activity is controlled spatiotemporally using light. By controlling the geometry and the duration of myosin activation, we show that contraction of disordered actin networks is highly cooperative, telescopic with the activation size, and capable of generating non-uniform patterns of mechanical stress. We quantitatively reproduce these collective biomimetic properties using an isotropic active gel model of the actomyosin cytoskeleton, and explore the physical origins of telescopic contractility in disordered networks using agent-based simulations. PMID- 27558759 TI - Reed Sternberg cell/lymphocyte rosettes in a bone marrow aspirate leading to the diagnosis of Hodgkin lymphoma. PMID- 27558760 TI - Medication Nonadherence: The Role of Cost, Community, and Individual Factors. AB - OBJECTIVE: To explain the association of out-of-pocket (OOP) cost, community level factors, and individual characteristics on statin therapy nonadherence. DATA SOURCES: BlueCross BlueShield of Texas claims data for the period of 2008 2011. STUDY DESIGN: A retrospective cohort of 49,176 insured patients, aged 18-64 years, with at least one statin refill during 2008-2011 was analyzed. Using a weighted proportion of days covered ratio, differences between adherent and nonadherent groups are assessed using chi-squared tests, t-tests, and a clustered generalized linear model with logit link function. PRINCIPAL FINDINGS: Statin therapy adherence, measured at 48 percent, is associated with neighborhood-level socioeconomic factors, including race/ethnicity, educational attainment, and poverty level. Individual characteristics influencing adherence include OOP medication cost, gender, age, comorbid conditions, and total health care utilization. CONCLUSIONS: This study signifies the importance of OOP costs as a determinant of adherence to medications, but more interestingly, the results suggest that other socioeconomic factors, as measured by neighborhood-level variables, have a greater association on the likelihood of adherence. The results may be of interest to policy makers, benefit designers, self-insured employers, and provider organizations. PMID- 27558761 TI - Hedgehog-BMP signalling establishes dorsoventral patterning in lateral plate mesoderm to trigger gonadogenesis in chicken embryos. AB - The gonad appears in the early embryo after several events: cells at the lateral plate mesoderm (LPM) undergo ingression, begin gonadal differentiation and then retain primordial germ cells (PGCs). Here we show that in the chicken embryo, these events are triggered on the basis of dorsoventral patterning at the medial LPM. Gonadal progenitor cells (GPCs) at the ventromedial LPM initiate gonadogenesis by undergoing ingression, whereas mesonephric capsule progenitor cells (MCPCs) at the dorsomedial LPM do not. These contrasting behaviours are caused by Hedgehog signalling, which is activated in GPCs but not in MCPCs. Inhibiting Hedgehog signalling prevents GPCs from forming gonadal structures and collecting PGCs. When activated by Hedgehog signalling, MCPCs form an ectopic gonad. This Hedgehog signalling is mediated by BMP4. These findings provide insight into embryonic patterning and gonadal initiation in the chicken embryo. PMID- 27558763 TI - Modeling the second stage of labor. AB - Vaginal delivery is the primary cause of levator ani muscle injury, which is in turn the leading factor contributing to pelvic floor disorders including pelvic organ prolapse and urinary stress incontinence. Existing biomechanical models of childbirth have provided some understanding of pelvic floor function during delivery and have helped in the investigation of preventative strategies. The modeling frameworks for childbirth simulation are described with emphasis on (1) the recent advances in medical imaging quality and computational power; (2) improvements in the anatomical representation of the pelvic floor and fetal head; (3) more realistic boundary conditions for delivery; and (4) mechanical properties determined from experiments. Researchers have used these models to analyze childbirth mechanics and identify anatomical and mechanical features of the maternal pelvic floor, shape of the fetal head, and delivery techniques that potentially contribute to a difficult labor and higher risk of levator ani muscle injuries. The challenges to be addressed for these frameworks to be clinically useful are also discussed, including: (1) the improvements required to more accurately simulate the second stage of labor; (2) automatic segmentation of medical images and creation of customized computer models; (3) acquisition of individual specific pelvic floor mechanical properties; and (4) construction of statistical models for rapidly predicting the indices of childbirth mechanics. Within the next decade, it is likely that biomechanical models of childbirth will be sufficiently well informed and functional for personalized birth planning, and as educational tools for clinicians. WIREs Syst Biol Med 2016, 8:506-516. doi: 10.1002/wsbm.1351 For further resources related to this article, please visit the WIREs website. PMID- 27558762 TI - Culture and Comorbidity: Intimate Partner Violence as a Common Risk Factor for Maternal Mental Illness and Reproductive Health Problems among Former Child Soldiers in Nepal. AB - Our objective was to elucidate how culture influences internal (psychological), external (social), institutional (structural), and health care (medical) processes, which, taken together, create differential risk of comorbidity across contexts. To develop a conceptual model, we conducted qualitative research with 13 female child soldiers in Nepal. Participants gave open-ended responses to intimate partner violence (IPV) vignettes (marital rape, emotional abuse, violence during pregnancy). Twelve participants (92%) endorsed personal responses (remaining silent, enduring violence, forgiving the husband). Twelve participants endorsed communication with one's husband. Only four participants (31%) sought family support, and three contacted police. Ultimately, 12 participants left the relationship, but the majority (nine) only left after the final IPV experience, which was preceded by prolonged psychological suffering and pregnancy endangerment. In conclusion, comorbidity risks are increased in cultural context that rely on individual or couples-only behavior, lack external social engagement, have weak law and justice institutions, and have limited health services. PMID- 27558764 TI - Atypical pityriasis rosea: clinical evaluation of 27 patients. AB - BACKGROUND: Pityriasis rosea (PR) is a common, acute, self-limiting inflammatory skin disease. It can easily be recognized with its typical clinical presentation. However, unusual clinic presentations can cause difficulty in diagnosis. Up to now, not many atypical forms are reported. OBJECTIVE: To determine the clinical characteristics of patients with atypical pityriasis rosea. METHODS: A total of 27 cases, diagnosed as atypical PR by clinical and/or histopathological examination and applied to the outpatient clinic of dermatology department between the years 2007 and 2015 were analyzed retrospectively. RESULTS: The ages of patients ranged from 2 to 59 years. Of these patients, 15 (55.6%) were male and 12 (44.4%) were female. The male-to-female ratio was 5-4. Five patients had papular, four patients had purpuric, three patients had vesicular, two patients had follicular, one patient had erythema multiforme-like and one patient had eczematous drug-induced atypical form of pityriasis rosea. There were 12 cases of localized, two cases of segmental pityriasis rosea. Four of the localized forms also had atypical morphology. Histopathological evaluation was required for diagnosis in 12 (44.4%) patients. CONCLUSIONS: PR can appear in many different uncommon forms. Localization and skin rush can be misleading and diagnosis can be compelling. PMID- 27558766 TI - Red Mud as an Efficient, Stable, and Cost-Free Catalyst for COx-Free Hydrogen Production from Ammonia. AB - Red mud, one of the mostly produced industrial wastes, was converted into a catalyst with exceptionally high and stable performance for hydrogen production from ammonia. Results showed that iron species produced after reduction of the HCl digested red mud were converted into epsilon-Fe2N during the induction period of ammonia decomposition reaction at 700 degrees C. The catalytic performance measurements indicated that the modified red mud catalyst provides a record high hydrogen production rate for a non-noble metal catalyst at this temperature. For instance, stable hydrogen production rates were measured as 72 and 196 mmol H2 min(-1) gcat(-1) for the corresponding space velocities of 72 000 and 240 000 cm(3) NH3 h(-1) gcat(-1), respectively, at 700 degrees C. These results offer opportunities to utilize one of the key hazardous industrial wastes as an eco friendly, efficient, stable, and almost cost-free catalyst for COx-free hydrogen production from ammonia decomposition. PMID- 27558765 TI - Native cellulose nanofibrills induce immune tolerance in vitro by acting on dendritic cells. AB - Cellulose nanofibrills (CNFs) are attractive biocompatible, natural nanomaterials for wide biomedical applications. However, the immunological mechanisms of CNFs have been poorly investigated. Considering that dendritic cells (DCs) are the key immune regulatory cells in response to nanomaterials, our aim was to investigate the immunological mechanisms of CNFs in a model of DC-mediated immune response. We found that non-toxic concentrations of CNFs impaired the differentiation, and subsequent maturation of human monocyte-derived (mo)-DCs. In a co-culture with CD4(+)T cells, CNF-treated mo-DCs possessed a weaker allostimulatory and T helper (Th)1 and Th17 polarizing capacity, but a stronger capacity to induce Th2 cells and CD4(+)CD25(hi)FoxP3(hi) regulatory T cells. This correlated with an increased immunoglobulin-like transcript-4 and indolamine dioxygenase-1 expression by CNF treated mo-DCs, following the partial internalization of CNFs and the accumulation of CD209 and actin bundles at the place of contacts with CNFs. Cumulatively, we showed that CNFs are able to induce an active immune tolerance by inducing tolerogenic DCs, which could be beneficial for the application of CNFs in wound healing and chronic inflammation therapies. PMID- 27558767 TI - Development of the cardiorespiratory system in dogs from days 16 to 46 of pregnancy. AB - Dogs have been studied for several reasons, such as the genetic improvement, their use as experimental models, in zoonotic research, cell therapy and as a model for human diseases. However, many features relating to the embryonic development of dogs remain unknown because of the absence of embryological studies. Considering the importance of the cardiorespiratory system in the development of embryos, the aim of this study was to investigate the development of the main cardiorespiratory organs of dog embryos and foetuses with estimated gestational ages from 16 to 46 days using macro- and microscopic descriptions. On day 16 of development, the neural tube and crest were formed, the anterior and posterior neuropore closure had begun and the somites had developed. Between days 22 and 27 of gestation, the lung buds and the initial formation of the primary bronchi and heart chambers were observed. The heart chambers exhibited the endo-, myo- and epicardial layers but did not have obvious differences in thickness among each other. Between days 41 and 46 of gestation, the nasal conchae and septa and trachea were formed, which exhibited characteristic epithelia. The lung formation and lobation were complete. The heart and major vessels exhibited mature histological architecture when their anatomical development was complete. The results of this study contribute to a more accurate definition of the embryonic and foetal developmental stages in dogs. PMID- 27558768 TI - Protective effect of mycophenolate mofetil on residual renal function in peritoneal dialysis patients: An open label feasibility study. AB - AIM: This study aims to evaluate the safety of mycophenolate mofetil (MMF) and its effect on residual renal function (RRF) during peritoneal dialysis (PD). METHODS: This is a prospective, randomized study comprising 60 PD patients. The patients were assigned either to the MMF group (MMF dosage: 1.0-1.5 g/day in two divided doses for 6 months, followed by a dose of 0.5-0.75 g/day for another 6 months) or to the control group. The patients close monitoring for 1 year. Variables related to residual renal function, including urine volume, measured glomerular filtration rate (GFR), and renal Kt/V, were measured at four time points. RESULTS: There were no significant changes in urinary protein excretion in either group (P > 0.05). The MMF group showed a significantly higher urine volume than the control group (955.38 +/- 243.54 vs 786.15 +/- 279.62 mL/day, P = 0.024). The renal kt/V was also significantly higher in the MMF group (0.59 +/- 0.11 in MMF vs 0.50 +/- 0.19 in control group, P = 0.032). There was significant difference in the renal measured GFR between the two groups at 6, 9 and 12 months (MMF vs control at 6 months, 6.14 +/- 0.66 vs 5.58 +/- 0.65 mL/min per 1.73m2 , P = 0.003; at 9 months, 5.68 +/- 0.80 vs 4.78 +/- 0.75, P < 0.001; at 12 months, 5.44 +/- 0.91 vs 4.43 +/- 0.93, P < 0.001). MMF was well tolerated without any serious complications. CONCLUSION: The use of MMF in PD patients tends to better preserve RRF. PMID- 27558771 TI - Association of Central Sleep Apnea with Impaired Heart Structure and Cardiovascular Hemodynamics in Patients with Chronic Heart Failure. AB - BACKGROUND Advanced heart failure (HF) is commonly accompanied by central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR). The aim of this study was to evaluate the relationship between CSA/CSR and other clinical features of HF, with particular emphasis on cardiovascular hemodynamics. MATERIAL AND METHODS In 161 stable HF patients with left ventricular ejection fraction (LVEF) <=45% (NYHA class I-III; mean LVEF 32.8%) the clinical evaluation included: LVEF; left and right ventricular end-diastolic diameter (LVDd, RVDd); ratio of early transmitral flow velocity to early diastolic septal mitral annulus velocity (E/e') assessed by echocardiography; stroke index (SI); heart rate (HR); cardiac index (CI); and systemic vascular resistance index (SVRI) assessed by impedance cardiography (ICG). The comparison was performed between 2 subgroups: one with moderate/severe CSA/CSR - CSR_ [+] (n=51), and one with mild or no CSA/CSR - CSR_ [-] (n=110). RESULTS CSR_ [+] patients presented more advanced NYHA class (p<0.001) and more frequently had permanent atrial fibrillation (p=0.018). Moreover, they had: lower LVEF (p<0.0001); higher LVDd (p<0.0001), RVDd (p<0.001), and E/e' (p<0.001); lower SI (p<0.001) and CI (p=0.009); and higher HR (p=0.044) and SVRI (p=0.016). The following predictors of CSR_ [+] were identified: NYHA class (OR=3.34 per class, p<0.001, which was the only independent predictor); atrial fibrillation (OR=2.29, p=0.019); RV enlargement (OR=2.75, p=0.005); LVEF<35% (OR=3.38, p=0.001); E/e' (OR=3.15; p=0.003); and SI<35 ml/m2 (OR=2.96, p=0.003). CONCLUSIONS Presence of CSA/CSR in HF is associated with NYHA class, atrial fibrillation and more advanced impairment of cardiovascular structure and hemodynamics. Patient functional state remains the main determinant of CSR. PMID- 27558772 TI - SpectralAnalysis: Software for the Masses. AB - The amount of data produced by spectral imaging techniques, such as mass spectrometry imaging, is rapidly increasing as technology and instrumentation advances. This, combined with an increasingly multimodal approach to analytical science, presents a significant challenge in the handling of large data from multiple sources. Here, we present software that can be used through the entire analysis workflow, from raw data through preprocessing (including a wide range of methods for smoothing, baseline correction, normalization, and image generation) to multivariate analysis (for example, memory efficient principal component analysis (PCA), non-negative matrix factorization (NMF), maximum autocorrelation factor (MAF), and probabilistic latent semantic analysis (PLSA)), for data sets acquired from single experiments to large multi-instrument, multimodality, and multicenter studies. SpectralAnalysis was also developed with extensibility in mind to stimulate development, comparisons, and evaluation of data analysis algorithms. PMID- 27558775 TI - 'Spiritual care is not the hospital's business': a qualitative study on the perspectives of patients about the integration of spirituality in healthcare settings. AB - BACKGROUND: Several studies have investigated the relationship between spirituality and health. They claim the need to develop spiritual care to answer patients' spiritual suffering and to promote spiritual well-being. However, the present study critically analyses the following idea: we ought to take care of the spiritual dimension of patients. Does this interest for spirituality not come from healthcare professionals' desire more than from the patients themselves? OBJECTIVE: To answer this question, we explored the perspectives of individuals with cancer regarding the integration of spirituality in the healthcare setting. DESIGN: Qualitative design using semistructured interviews to focus on subjective experience. SETTING: One of the major public hospitals of Paris, France. PARTICIPANTS: 20 participants (n=11 men and n=9 women) with advanced cancer (stage IV). Age ranges from 37 to 80 years with a mean age of 58.7 years. RESULTS: Findings demonstrated that participants do not expect help from the hospital to handle spiritual issues but they wish for their spiritual dimension to be simply recognised as a part of their identity and dignity. CONCLUSIONS: Findings invite us to view the question of spirituality not as a new dimension of care but as a new challenge for healthcare institutions to recognise that the persons they are working for are not just 'patients' but human beings with a precious interior life. PMID- 27558773 TI - Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine. AB - Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as gamma rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract. PMID- 27558774 TI - Population pharmacokinetics and analgesic potency of oxycodone. AB - AIMS: This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra-abdominal surgery. METHODS: In the pharmacokinetic study, patients were administered intravenous oxycodone (0.1 mg kg-1 ), and arterial blood was sampled at pre-set intervals. In the analgesic-potency study, patients were administered intravenous oxycodone (0.1 mg kg-1 ) 30 min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as >=3 or >=5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2 mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient. RESULTS: In the population pharmacokinetic study (n = 54), oxycodone plasma concentration over time was well described by a three-compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic-potency study (n = 50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2-42.8) and 74.1 (29.2-128.3) ng ml-1 (first measurements) and 63.4 (15.6-120.1) and 76.1 (32.9 132.7) ng ml-1 (second measurements), respectively. CONCLUSIONS: In major intra abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75 ng ml 1 and 60 ng ml-1 , respectively. PMID- 27558776 TI - Climate change, cooperation and moral bioenhancement. AB - The human faculty of moral judgement is not well suited to address problems, like climate change, that are global in scope and remote in time. Advocates of 'moral bioenhancement' have proposed that we should investigate the use of medical technologies to make human beings more trusting and altruistic and hence more willing to cooperate in efforts to mitigate the impacts of climate change. We survey recent accounts of the proximate and ultimate causes of human cooperation in order to assess the prospects for bioenhancement. We identify a number of issues that are likely to be significant obstacles to effective bioenhancement, as well as areas for future research. PMID- 27558778 TI - Appropriate handling of pet rabbits: a literature review. AB - Many rabbits show fear behaviours when lifted off the ground. Estimates from owner surveys suggest that around 60% of pet rabbits struggle when lifted and fear-related aggression is common. This article integrates information from both laboratory and pet rabbit studies to formulate a list of recommendations for appropriate handling of rabbits. Reduction of the frequency of the stressor can be achieved by educating owners on alternative management practices to reduce the need to carry their rabbits. However, in some situations, it is unavoidable that a rabbit is lifted. Amelioration of the stress in these instances can be achieved by a 2 pronged strategy. First, the population of rabbits can be made more resilient to infrequent stressors by selectively breeding for confident rabbits and by better socialisation of unweaned kits, and, where possible, training of individual animals to permit handling. Secondly, any unavoidable lifting can be made less stressful by educating veterinary staff in appropriate methods of holding rabbits during both consultations and inpatient care. Better understanding of appropriate interactions with rabbits will improve welfare. PMID- 27558777 TI - Quantitative proteomic comparison of stationary/G0 phase cells and tetrads in budding yeast. AB - Most of the microbial cells on earth under natural conditions exist in a dormant condition, commonly known as quiescent state. Quiescent cells exhibit low rates of transcription and translation suggesting that cellular abundance of proteins may be similar in quiescent cells. Therefore, this study aim to compare the proteome of budding yeast cells from two quiescent states viz. stationary phase/G0 and tetrads. Using iTRAQ (isobaric tag for relative and absolute quantitation) based quantitative proteomics we identified 289 proteins, among which around 40 proteins exhibited +/-1.5 fold change consistently from the four biological replicates. Proteomics data was validated by western blot and denstiometric analysis of Hsp12 and Spg4. Level of budding yeast 14-3-3 proteins was found to be similar in both the quiescent states, whereas Hsp12 and Spg4 expressed only during stress. FACS (fluorescence-activated cell sorting) analysis showed that budding yeast cells were arrested at G1 stages both in tetrads as well as in stationary phase. We also observed that quiescent states did not express Ime1 (inducer of meiosis). Taken together, our present study demonstrates that the cells in quiescent state may have similar proteome, and accumulation of proteins like Hsp12, Hsp26, and Spg4 may play an important role in retaining viability of the cells during dormancy. PMID- 27558780 TI - Chapter 2 - Diagnostics. PMID- 27558779 TI - Effect of a non-woven fabric covering on the residual activity of pendimethalin in lettuce and soil. AB - BACKGROUND: Lettuce (Lactuca sativa L.) is a crop that is very sensitive to herbicide contamination owing to its short growing season. The use of long residual herbicides and non-woven fabric coverings could therefore influence pendimethalin concentrations in soil and lettuce. RESULTS: The pendimethalin half life in soil ranged between 18 and 85 days and was mainly affected by season (i.e. weather), and especially by soil moisture. Pendimethalin degradation in soil was slowest under dry conditions. A longer pendimethalin half-life was observed under the non-woven fabric treatment, but the effect of varying application rate was not significant. Pendimethalin residue concentrations in lettuce heads were significantly influenced by pendimethalin application rate and by non-woven fabric cover, especially at the lettuce's early growth stages. The highest pendimethalin concentration at final harvest was determined in lettuce grown on uncovered plots treated with pendimethalin at an application rate of 1200 g ha-1 (7-38 ug kg-1 ). Depending on growing season duration and weather conditions, pendimethalin concentrations in lettuce grown under non-woven fabric ranged from 0 to 21 ug kg-1 . CONCLUSION: Use of transparent non-woven fabric cover with lettuce can help to reduce application rates of soil herbicides and diminish the risk of herbicide contamination in the harvested vegetables. (c) 2016 Society of Chemical Industry. PMID- 27558781 TI - Metagenomic applications in environmental monitoring and bioremediation. AB - With the rapid advances in sequencing technology, the cost of sequencing has dramatically dropped and the scale of sequencing projects has increased accordingly. This has provided the opportunity for the routine use of sequencing techniques in the monitoring of environmental microbes. While metagenomic applications have been routinely applied to better understand the ecology and diversity of microbes, their use in environmental monitoring and bioremediation is increasingly common. In this review we seek to provide an overview of some of the metagenomic techniques used in environmental systems biology, addressing their application and limitation. We will also provide several recent examples of the application of metagenomics to bioremediation. We discuss examples where microbial communities have been used to predict the presence and extent of contamination, examples of how metagenomics can be used to characterize the process of natural attenuation by unculturable microbes, as well as examples detailing the use of metagenomics to understand the impact of biostimulation on microbial communities. PMID- 27558782 TI - Engineering levoglucosan metabolic pathway in Rhodococcus jostii RHA1 for lipid production. AB - Oleaginous strains of Rhodococcus including R. jostii RHA1 have attracted considerable attention due to their ability to accumulate triacylglycerols (TAGs), robust growth properties and genetic tractability. In this study, a novel metabolic pathway was introduced into R. jostii by heterogenous expression of the well-characterized gene, lgk encoding levoglucosan kinase from Lipomyces starkeyi YZ-215. This enables the recombinant R. jostii RHA1 to produce TAGs from the anhydrous sugar, levoglucosan, which can be generated efficiently as the major molecule from the pyrolysis of cellulose. The recombinant R. jostii RHA1 could grow on levoglucosan as the sole carbon source, and the consumption rate of levoglucosan was determined. Furthermore, expression of one more copy of lgk increased the enzymatic activity of LGK in the recombinant. However, the growth performance of the recombinant bearing two copies of lgk on levoglucosan was not improved. Although expression of lgk in the recombinants was not repressed by the glucose present in the media, glucose in the sugar mixture still affected consumption of levoglucosan. Under nitrogen limiting conditions, lipid produced from levoglucosan by the recombinant bearing lgk was up to 43.54 % of the cell dry weight, which was comparable to the content of lipid accumulated from glucose. This work demonstrated the technical feasibility of producing lipid from levoglucosan, an anhydrosugar derived from the pyrolysis of lignocellulosic materials, by the genetically modified rhodococci strains. PMID- 27558783 TI - Determinants of quality of life in community-dwelling older adults: comparing three cut-offs on the excellent-to-poor spectrum. AB - PURPOSE: The aim of this study was to identify modifications in health, economic and social determinants of quality of life (QoL) in community-dwelling older adults when using different cut-offs to defining favorable QoL. METHODS: Data of year 2011 annual assessment in 1003 older men and women from the Lc65+ cohort study were used. Overall QoL was self-rated as 'excellent,' 'very good,' 'good,' 'fair,' or 'poor.' To identify significant health (self-rated health, SF-12v2 physical and mental health), economic (financial situation), and social (living with others, being socially supported, emotional support, group activities participation) determinants of QoL, a cut-off was set at three different positions to define favorable QoL on the 'excellent' to 'poor' spectrum: at least 'good' (model 1); at least 'very good' (model 2); and 'excellent' only (model 3). RESULTS: In all three models, bivariable analyses indicated significant associations between QoL and at least one variable from each health, economic, and social dimension. In multivariable analyses, only health-related variables remained significantly associated with QoL in model 1. Model 3 additionally retained financial situation. In model 2, QoL was positively associated with physical health [odds ratio (OR) 1.10, p < 0.001], mental health (OR 1.12, p < 0.001), self-rated health (OR 2.43, p < 0.001), group activities participation (OR 1.43, p = 0.037), being socially supported (OR 1.58, p = 0.024), and not reporting financial difficulties (OR 1.76; p = 0.036). CONCLUSIONS: Using different cut-offs to defining favorable QoL results in important changes in the number and type of significant health, economic and social determinants. A cut off between 'good' and 'very good' appears to best reflect the multidimensional nature of QoL. PMID- 27558784 TI - Quality of life of pediatric oncology patients: Do patient-reported outcome instruments measure what matters to patients? AB - PURPOSE: The assessment of quality of life (QOL) is key within pediatric oncology and requires a clearly defined construct of QOL. The purpose of our study was: (1) to conduct a qualitative study to inform the theoretical underpinnings of QOL and (2) to determine the appropriateness of patient-reported outcome (PRO) instruments to assess and evaluate QOL in pediatric cancer patients and survivors. METHODS: The study used an interpretative description approach. Children diagnosed with childhood cancer, aged 8-18 years, were recruited from four Canadian hospitals. Semi-structured interviews were completed, transcribed verbatim and coded through methods of constant comparison. In-depth analysis facilitated a comparison between emerging themes and the content of commonly used PRO instruments. RESULTS: Thirty-seven children (19 females; 51 %) participated. The mean age was 13 years, and 19 (51 %) participants were post-treatment. Participant experiences reflected notions of positive and negative duality, including: maintaining physical functioning but longing for the ability to participate in activities; experiencing a new level of intimacy with family and friends amidst isolation; and developing positivity amidst anger, sadness and lingering worry. Analysis showed that existing PRO instruments are missing concerns specific to this population and contain content not reflective of the QOL experiences of childhood cancer patients and survivors. CONCLUSIONS: Our research highlights important problems with content validity of existing PRO scales, indicating that the tools we have to date have limited utility in research and clinical practice. The development of a new PRO instrument should be considered to ensure that content validity is achieved. PMID- 27558785 TI - Reducing respondent burden: validation of the Brief Impact of Vision Impairment questionnaire. AB - PURPOSE: To develop a psychometrically sound and valid Brief Impact of Vision Impairment (IVI) questionnaire. METHODS: Cross-sectional data from four prospective studies (2001-2008) were pooled and randomly divided into development/validation sets (n = 416) each. Items with suboptimal psychometric properties were iteratively removed in the development set to form the Brief IVI. Psychometric properties of the Brief IVI were independently tested in the validation sample. Correlation between person measures from the original and Brief IVI was assessed [Pearson r and intraclass correlation coefficient (ICC)]. Criterion validity was determined by testing the Brief IVI's ability to discriminate levels of vision impairment (analysis of variance, ANOVA). Responsiveness was tested by comparing the ICC of the original and Brief IVI data obtained pre-/post-intervention. RESULTS: The 15-item Brief IVI, and its 9-item Visual Functioning and 6-item Emotional Well-being subscales had ordered thresholds, good precision and targeting, unidimensionality, and minimal item misfit (replicated in the validation sample). Brief and original IVI person measures were highly correlated (r = 0.97 and ICC = 0.98, p < 0.001), indicating the Brief IVI provides statistically similar measurement of vision-related quality of life (VRQoL). Brief IVI mean logit scores declined as vision impairment worsened (p = 0.001) demonstrating criterion validity. ICC of the original versus Brief IVI pre-/post-intervention was excellent (0.98), establishing that the Brief IVI was as responsive to changes in VRQoL as the original. CONCLUSIONS: The Brief 15-item IVI can obtain valid and responsive measurement of VRQoL with half the items in the original and has potential to reduce respondent burden in QoL studies. PMID- 27558786 TI - Insight into Prodrugs of Quinolones and Fluoroquinolones. AB - Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy. PMID- 27558787 TI - Dry Season Constrains Bacterial Phylogenetic Diversity in a Semi-Arid Rhizosphere System. AB - The rhizosphere is viewed as a deterministic environment led by the interaction between plants and microorganisms. In the case of semi-arid plants, this interaction is strengthened by the harshness of the environment. We tested the hypothesis that dry season represents a constraint on the bacterial diversity of the rhizosphere from semi-arid plants. To accomplish this, we sampled two leguminous species at five locations during the dry and rainy seasons in the Caatinga biome and characterised bacterial community structures using qPCR and 16S rRNA sequencing. We found that the main differences between seasons were due to reduced phylogenetic diversity caused by dryness. Variation partitioning indicated that environmental characteristics significant impacts in beta diversity. Additionally, distance decay relationship and taxa area relationship indicate a higher spatial turnover at the rainy season. During the dry season, decreased bacterial abundance is likely due to the selection of resistant or resilient microorganisms; with the return of the rain, the sensitive populations start to colonise the rhizosphere by a process that is strongly influenced by environmental characteristics. Thus, we propose that the reduction of PD and strong influence of environmental parameters on the assemblage of these communities make them prone to functional losses caused by climatic disturbances. PMID- 27558788 TI - Electrophysiological and Behavioral Effects of Combined Transcranial Direct Current Stimulation and Alcohol Approach Bias Retraining in Hazardous Drinkers. AB - BACKGROUND: Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying mechanisms by including behavioral (craving, implicit associations, approach tendencies) and electrophysiological (event-related potentials) measurements. METHODS: The analytical sample consisted of 78 hazardous drinkers (Alcohol Use Disorders Identification Test >8) randomly assigned to 4 conditions in a 2-by-2 factorial design (control/active CBM and sham/active tDCS). The intervention consisted of 3 sessions of CBM, specifically alcohol approach bias retraining, combined with 15 minutes 1 mA tDCS over the left dorsolateral prefrontal cortex. There was a pre- and postassessment before and after the intervention that included experimental tasks (Approach Avoidance Task, Implicit Association Task) and an electroencephalogram with an oddball and cue-reactivity task. RESULTS: tDCS decreased cue-induced craving (but not overall craving) on postassessment. CBM did not induce an avoidance bias during assessment. During the training, active and control-CBM only differed in bias score during the first session. We found no enhancement effects of tDCS on CBM. Electrophysiological data showed no clear effects of active tDCS or CBM on the P300. CONCLUSIONS: There were no electrophysiological or behavioral effects of repeated CBM and/or tDCS, except for an effect of tDCS on craving. Applied in these specific ways these techniques appear to have limited effects in a hazardous drinking population. PMID- 27558789 TI - Non-echoplanar diffusion weighted imaging in the detection of post-operative middle ear cholesteatoma: navigating beyond the pitfalls to find the pearl. AB - Non-echoplanar diffusion weighted magnetic resonance imaging (DWI) has established itself as the modality of choice in detecting and localising post operative middle ear cleft cholesteatoma. Despite its good diagnostic performance, there are recognised pitfalls in its radiological interpretation which both the radiologist and otologist should be aware of. Our article highlights the various pitfalls and provides guidance for improving radiological interpretation and navigating beyond many of the pitfalls. It is recommended radiological practice to interpret the diffusion weighted images together with the ADC map and supplement with the corresponding T1 weighted and T2 weighted images, all of which can contribute to and enhance lesion localisation and characterisation. ADC values are also helpful in improving specificity and confidence levels. Given the limitation in sensitivity in detecting small cholesteatoma less than 3 mm, serial monitoring with DWI over time is recommended to allow any small residual cholesteatoma pearls to grow and become large enough to be detected on DWI. Optimising image acquisition and discussing at a joint clinico-radiological meeting both foster good radiological interpretation to navigate beyond the pitfalls and ultimately good patient care. TEACHING POINTS: * Non-echoplanar DWI is the imaging of choice in detecting post-operative cholesteatoma. * There are recognised pitfalls which may hinder accurate radiological interpretation. * Interpret with the ADC map /values and T1W and T2W images. * Serial DWI monitoring is of value in detection and characterisation. * Optimising image acquisition and discussing at clinico-radiological meetings enhance radiological interpretation. PMID- 27558790 TI - Differential role of hypothalamic orexin/hypocretin neurons in reward seeking motivated by cocaine versus palatable food. AB - Hypothalamic orexin/hypocretin (Orx/Hcrt) neurons are thought to mediate both food-reinforced behaviors and behavior motivated by drugs of abuse. However, the relative role of the Orx/Hcrt system in behavior motivated by food versus drugs of abuse remains unclear. This investigation addressed this question by contrasting hypothalamic Orx/Hcrt neuronal activation associated with reinstatement of reward seeking induced by stimuli conditioned to cocaine (COC) versus highly palatable food reward, sweetened condensed milk (SCM). Orx/Hcrt neuronal activation in the lateral hypothalamus, dorsomedial hypothalamus and perifornical area, determined by dual c-fos/orx immunocytochemistry, was quantified in rat brains, following reinstatement of reward seeking induced by a discriminative stimulus (S+ ) conditioned to COC or SCM. The COC S+ and SCM S+ initially produced the same magnitude of reward seeking. However, over four subsequent tests, behavior induced by the SCM S+ decreased to extinction levels, whereas reinstatement induced by the COC S+ perseverated at undiminished levels. Following both the first and fourth tests, the percentage of Orx/Hcrt cells expressing Fos was significantly increased in all hypothalamic subregions in rats tested with the COC S+ but not rats tested with the SCM S+ . These findings point toward a role for the Orx/Hcrt system in perseverating, compulsive-like COC seeking but not behavior motivated by palatable food. Moreover, analysis of the Orx/Hcrt recruitment patterns suggests that failure of Orx/Hcrt neurons in the lateral hypothalamus to respond to inhibitory inputs from Orx/Hcrt neurons in the dorsomedial hypothalamus/perifornical area may contribute to the perseverating nature of COC seeking. PMID- 27558791 TI - Visual motion detection and habitat preference in Anolis lizards. AB - The perception of visual stimuli has been a major area of inquiry in sensory ecology, and much of this work has focused on coloration. However, for visually oriented organisms, the process of visual motion detection is often equally crucial to survival and reproduction. Despite the importance of motion detection to many organisms' daily activities, the degree of interspecific variation in the perception of visual motion remains largely unexplored. Furthermore, the factors driving this potential variation (e.g., ecology or evolutionary history) along with the effects of such variation on behavior are unknown. We used a behavioral assay under laboratory conditions to quantify the visual motion detection systems of three species of Puerto Rican Anolis lizard that prefer distinct structural habitat types. We then compared our results to data previously collected for anoles from Cuba, Puerto Rico, and Central America. Our findings indicate that general visual motion detection parameters are similar across species, regardless of habitat preference or evolutionary history. We argue that these conserved sensory properties may drive the evolution of visual communication behavior in this clade. PMID- 27558792 TI - DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention. AB - Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. PMID- 27558793 TI - Highly fluorescent gold nanoclusters stabilized by food proteins: From preparation to application in detection of food contaminants and bioactive nutrients. AB - Applications of nanotechnology in food have rapidly increased in the past decades. Ultra-small gold nanoclusters (Au NCs), composed of several to roughly a hundred atoms, represent a kind of novel nanomaterials. The Au NCs directed by food proteins have drawn considerable research attention due to their environment friendly preparation, strong fluorescence, excellent photo-stability, and favorable biocompatibility. These interesting protein-Au hybrids have opened up a new area at the nano-bio-food interface, not only did they provide the missing link between single metal atoms and plasmonic metal nanoparticles, but also developed the hybrid system between biomacromolecule and inorganic ions. In this review, we highlighted the synthesis strategies and optical properties of the Au NCs stabilized by typical food proteins as well as their applications in detection of food contaminants or bioactive nutrients. In addition, we discussed current challenges and future development in food proteins- directed gold nanoclusters for size-controlled synthesis and multifunctional applications. PMID- 27558794 TI - The importance of agricultural lands for Himalayan birds in winter. AB - The impacts of land-use change on biodiversity in the Himalayas are poorly known, notwithstanding widespread deforestation and agricultural intensification in this highly biodiverse region. Although intact primary forests harbor many Himalayan birds during breeding, a large number of bird species use agricultural lands during winter. We assessed how Himalayan bird species richness, abundance, and composition during winter are affected by forest loss stemming from agriculture and grazing. Bird surveys along 12 elevational transects within primary forest, low-intensity agriculture, mixed subsistence agriculture, and intensively grazed pastures in winter revealed that bird species richness and abundance were greatest in low-intensity and mixed agriculture, intermediate in grazed pastures, and lowest in primary forest at both local and landscape scales; over twice as many species and individuals were recorded in low-intensity agriculture than in primary forest. Bird communities in primary forests were distinct from those in all other land-use classes, but only 4 species were unique to primary forests. Low-, medium-, and high-intensity agriculture harbored 32 unique species. Of the species observed in primary forest, 80% had equal or greater abundance in low intensity agricultural lands, underscoring the value of these lands in retaining diverse community assemblages at high densities in winter. Among disturbed landscapes, bird species richness and abundance declined as land-use intensity increased, especially in high-intensity pastures. Our results suggest that agricultural landscapes are important for most Himalayan bird species in winter. But agricultural intensification-especially increased grazing-will likely result in biodiversity losses. Given that forest reserves alone may inadequately conserve Himalayan birds in winter, comprehensive conservation strategies in the region must go beyond protecting intact primary forests and ensure that low intensity agricultural lands are not extensively converted to high-intensity pastures. PMID- 27558795 TI - Factors associated with disease expression patterns in systemic lupus erythematosus patients: results from LUMINA (LXXVII), a multiethnic US cohort. AB - Objective The objective of this study was to determine the association of disease expression patterns with demographic and clinical characteristics in SLE. Methods Patients from a multi-ethnic SLE cohort were included. Disease expression patterns were defined as acute SLE and insidious SLE; this group was divided into those who accrued three ACR criteria and then accrued the fourth (insidious pattern A) and those who have one or two and then accrued four criteria (insidious pattern B). Disease activity was ascertained with the SLAM-R and disease damage with SLICC/ACR damage index. Variables were compared using analysis of variance for numeric variables and chi2 for categorical variables. Multivariable analyses adjusting for possible confounders were performed. Results Six hundred and forty patients were included; the most frequent pattern was the insidious pattern B, with 415 (64.8%) patients, followed by the acute SLE group with 115 (18.0%) and the insidious pattern A with 110 (17.2%) patients. Patients from the insidious pattern A were older at diagnosis (pattern A: 39.8 vs pattern B: 36.7 vs acute: 32.4 years; p < 0.0001), more educated (13.6 vs 13.1 vs 12.1; p = 0.0008) and with a less active disease at baseline (8.8 vs 9.2 vs 10.7; p = 0.0227). Caucasian and Hispanic (Puerto Rico) ethnicities were overrepresented in this group (40.0% vs 27.7% vs 19.1% and 18.2% vs 17.1% vs 9.6%; p = 0.0003). Conclusions More insidious onset is associated with older age, Caucasian ethnicity, higher level of education, and lower disease activity than those with acute onset. However, after multivariable analyses, disease activity was not associated with any disease expression pattern. PMID- 27558796 TI - Genotypic variation in biomass allocation in response to field drought has a greater affect on yield than gas exchange or phenology. AB - BACKGROUND: Plant performance in agricultural and natural settings varies with moisture availability, and understanding the range of potential drought responses and the underlying genetic architecture is important for understanding how plants will respond to both natural and artificial selection in various water regimes. Here, we raised genotypes of Brassica rapa under well-watered and drought treatments in the field. Our primary goal was to understand the genetic architecture and yield effects of different drought-escape and dehydration avoidance strategies. RESULTS: Drought treatments reduced soil moisture by 62 % of field capacity. Drought decreased biomass accumulation and fruit production by as much as 48 %, whereas instantaneous water-use efficiency and root:shoot ratio increased. Genotypes differed in the mean value of all traits and in the sensitivity of biomass accumulation, root:shoot ratio, and fruit production to drought. Bivariate correlations involving gas-exchange and phenology were largely constant across environments, whereas those involving root:shoot varied across treatments. Although root:shoot was typically unrelated to gas-exchange or yield under well-watered conditions, genotypes with low to moderate increases in root:shoot allocation in response to drought survived the growing season, maintained maximum photosynthesis levels, and produced more fruit than genotypes with the greatest root allocation under drought. QTL for gas-exchange and yield components (total biomass or fruit production) had common effects across environments while those for root:shoot were often environment-specific. CONCLUSIONS: Increases in root allocation beyond those needed to survive and maintain favorable water relations came at the cost of fruit production. The environment-specific effects of root:shoot ratio on yield and the differential expression of QTL for this trait across water regimes have important implications for efforts to improve crops for drought resistance. PMID- 27558797 TI - Computational investigation on the host-guest inclusion process of norfloxacin into beta-cyclodextrin. AB - A theoretical (1)H NMR spectroscopy and thermodynamic analysis of the host-guest inclusion process involving the norfloxacin (NFX) into beta-cyclodextrin (beta CD) was carried out. DFT structure and stabilization energies were obtained in both gas and aqueous phases. We could establish that the complex formation is enthalpy driven, and the hydrogen bonds established between NFX and beta-CD play a major role in the complex stabilization. Besides, a theoretical (1)H NMR analysis has shown to be a supplementary proceeding to predict appropriately the inclusion mode of norfloxacin molecule into the beta-CD. In this work, a theoretical study of the NFX@beta-CD complex is reported for the first time, seeking a deep understanding of topology and thermodynamics of the inclusion complex formation. Graphical Abstract Topology, thermodynamic and (1)H NMR analysis of NFX@beta-CD host-guest complexes. PMID- 27558798 TI - Naratriptan aggregation in lipid bilayers: perspectives from molecular dynamics simulations. AB - In order to understand the interaction between naratriptan and a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC), we carried out molecular dynamics simulations. The simulations were performed considering neutral and protonated ionization states, starting from different initial conditions. At physiological pH, the protonated state of naratriptan is predominant. It is expected that neutral compounds could have larger membrane partition than charged compounds. However, for the specific case of triptans, it is difficult to study neutral species in membranes experimentally, making computer simulations an interesting tool. When the naratriptan molecules were originally placed in water, they partitioned between the bilayer/water interface and water phase, as has been described for similar compounds. From this condition, the drugs displayed low access to the hydrophobic environment, with no significant effects on bilayer organization. The molecules anchored in the interface, due mainly to the barrier function of the polar and oriented lipid heads. On the other hand, when placed inside the bilayer, both neutral and protonated naratriptan showed self-aggregation in the lipid tail environment. In particular, the protonated species exhibited a pore-like structure, dragging water through this environment. Graphical Abstract Different behaviour of Naratriptan and Sumatriptan, when the drugs were originally placed in the lipid core. PMID- 27558799 TI - De novo design of VEGFR-2 tyrosine kinase inhibitors based on a linked-fragment approach. AB - Vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors have been demonstrated to possess substantial antitumor activity. VEGFR-2 tyrosine kinase inhibitors are crucial for development of antitumor drugs. Based on the crystal structure of VEGFR-2 tyrosine kinase, a linked fragment strategy was employed to design novel VEGFR-2 tyrosine kinase inhibitors, and 1000 compounds were generated in this process. Absorption, distribution, metabolism, excretion and toxicity (ADMET) were used to screen the 1000 compounds, and 59 compounds were acceptable. Scaffold hopping was then used for further screening, and only four compounds were obtained in this way. Then, the binding energy of the four molecules to VEGFR-2 tyrosine kinase was calculated using molecular docking, and their values were found to be lower than that of Sorafenib. Finally, molecular dynamics simulations were performed on the complex of the compound with the lowest binding energy with VEGFR-2 tyrosine kinase, and the binding model was analyzed. At the end, four chemical entities with novel structures were obtained, and were suggested for experimental testing in future studies. PMID- 27558800 TI - Interaction of a Ti-doped semi-fullerene (TiC30) with molecules of CO and CO2. AB - Using density functional theory (DFT) and molecular dynamics (MD), we studied the interaction of a titanium atom with a half of a C60 fullerene (i.e., C30), formed from the corannulene structure with a pentagonal base. We considered atmospheric pressure and 300 K. We found that the most stable adsorption of the titanium atom on C30 occurs in the concave surface of the molecule. Afterward, we investigated the interaction of the system C30-titanium with carbon monoxide and carbon dioxide molecules, respectively. We found that each of these molecules is chemisorbed, with no dissociation. The value of the adsorption energy for the carbon monoxide molecule varies from -0.897 to -1.673 eV, and for the carbon dioxide molecule, it is between -1.065 and -1.274 eV. These values depend on the initial orientation of these molecules with respect to TiC30. Graphical Abstract The TiC30 system chemisorbs CO or CO2?with no dissociation at atmospheric pressure and 300K. PMID- 27558801 TI - Erratum to: Outcome of Rehabilitation and Swallowing Therapy after Percutaneous Endoscopic Gastrostomy in Dysphagia Patients. PMID- 27558802 TI - Chemical Genetic Screen Identifies Natural Products that Modulate Centriole Number. AB - Centrioles are microtubule-based organelles found in most eukaryotic cells and that are critical for the formation of cilia and flagella, as well as of centrosomes in animal cells. The number of centrioles must be strictly regulated in proliferating cells in order to ensure genome integrity upon cell division. Despite their importance, however, the mechanisms governing centriole assembly and number control remain incompletely understood, owing in part to a paucity of available small-molecule compounds for dissection and alteration of the underlying processes. Here we have developed a chemical genetic approach to identify small-molecule compounds capable of modulating centriole numbers in human cells. High-throughput screening of ~2600 natural compounds identified 14 candidate molecules that either diminish (ten compounds) or augment (four compounds) the number of centrioles per cell. We investigated the mechanisms of action of four of these compounds and discovered that two of them potentially reduce centriole number through effects on NF-kappaB signalling. Moreover, we established that one further compound blocks cell cycle progression and probably indirectly causes an augmentation of centriole number. The last compound analysed induces, in addition to excess centrioles, exceptionally long primary cilia-like structures. Overall, our analysis demonstrates that natural products constitute a rich source of tool compounds useful for unravelling and manipulating the mechanisms governing centriole assembly and number control. PMID- 27558803 TI - Concentration of polychlorinated biphenyl (PCB) congeners in the muscle of Clarias gariepinus and sediment from inland rivers of southwestern Nigeria and estimated potential human health consequences. AB - The distributions of polychlorinated biphenyl (PCB) congeners were determined in sediment and muscle of the African sharptooth catfish (Clarias gariepinus) from the Ogun and Ona rivers, southwest Nigeria. In addition, the effect of PCB congeners on condition factor (CF) and associated human health risk was assessed using muscle levels for a noncarcinogenic hazard quotient (HQ) calculation. Elevated concentrations of high-molecular-weight (HMW) PCB congeners were detected in sediment and fish downstream of discharge points of both rivers. A significant reduction in fish body weight and CF was observed to correlate with high PCB congener concentrations in the Ona River. A principal component (PC) biplot revealed significant site-related PCB congener distribution patterns for HMW PCB in samples from the Ogun River (71.3%), while the Ona River (42.6%) showed significant PCB congener patterns for low-molecular-weight (LMW) congeners. Biota-sediment accumulation factor (BSAF) was higher downstream for both rivers, presenting PCB congener-specific accumulation patterns in the Ona River. Significant decreases in fish body weight, length and CF were observed downstream compared to upstream in the Ona River. The non-carcinogenic HQ of dioxin-like congener 189 downstream in both rivers exceeded the HQ = 1 threshold for children and adults for both the Ogun and Ona rivers. Overall, our results suggest that industrial discharges contribute significantly to PCB inputs into these rivers, with potential for significant health implications for neighboring communities that utilize these rivers for fishing and other domestic purposes. PMID- 27558806 TI - ERRATUM. PMID- 27558804 TI - Pleiotropic roles of Ca+2/calmodulin-dependent pathways in regulating cadmium induced toxicity in human osteoblast-like cell lines. AB - The heavy metal cadmium is a widespread environmental contaminant that has gained public attention due to the global increase in cadmium-containing electronic waste. Human exposure to cadmium is linked to the pathogenesis of osteoporosis. We previously reported cadmium induces apoptosis and decreases alkaline phosphatase mRNA expression via extracellular signal-regulated protein kinase (ERK) activation in Saos-2 bone-forming osteoblasts. This study examines the mechanisms of cadmium-induced osteotoxicity by investigating roles of Ca+2/calmodulin-dependent protein kinase (CAMK) pathways. Saos-2 or MG-63 cells were treated for 24 or 48h with 5MUM CdCl2 alone or in combination with calmodulin-dependent phosphodiesterase (PDE) inhibitor CGS-9343beta; calmodulin dependent kinase kinase (CAMKK) inhibitor STO-609; or calmodulin-dependent kinase II (CAMKII) inhibitor KN-93. CGS-9343beta protected against cadmium-induced toxicity and attenuated ERK activation; STO-609 enhanced toxicity and exacerbated ERK activation, whereas KN-93 had no detectable effect on cadmium-induced toxicity. Furthermore, CGS-9343beta co-treatment attenuated cadmium-induced apoptosis; but CGS-9343beta did not recover cadmium-induced decrease in ALP activity. The major findings suggest the calmodulin-dependent PDE pathway facilitates cadmium-induced ERK activation leading to apoptosis, whereas the CAMKK pathway plays a protective role against cadmium-induced osteotoxicity via ERK signaling. This research distinguishes itself by identifying pleiotropic roles for CAMK pathways in mediating cadmium's toxicity in osteoblasts. PMID- 27558805 TI - NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic beta-cells. AB - NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic beta-cell metabolism under basal conditions and oxidant challenge have not been characterized. Using NQO1 inhibition, over-expression and knock out, we have demonstrated that, in addition to protection of beta-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides, suggesting other role(s) beside that of an antioxidant enzyme. In contrast, over-expression of NADPH cytochrome P450 oxidoreductase (CYP450OR) resulted in enhanced redox cycling activity and decreased cellular viability, consistent with the enhanced generation of superoxide and H2O2. Basal expression of NQO1 and CYP450OR was comparable in isolated islets and liver. However, NQO1, but not CYP450OR, was strongly induced in beta-cells exposed to menadione. NQO1 and CYP450OR exhibited a reciprocal preference for reducing equivalents in beta cells: while CYP450OR preferentially utilized NADPH, NQO1 primarily utilized NADH. Together, these results demonstrate that NQO1 and CYP450OR reciprocally regulate oxidant metabolism in pancreatic beta-cells. PMID- 27558809 TI - Pullout Fixation of Posterior Medial Meniscus Root Tears: Correlation Between Meniscus Extrusion and Midterm Clinical Results AB - BACKGROUND: Medial meniscus posterior root tears (MMPRTs) lead to extrusion of the meniscus during weightbearing as well as loss of the ability of the meniscus to generate hoop stress. This loss of load-sharing ability leads to progressive arthritic changes. However, there have been no studies that correlate the correction of meniscus extrusion with clinical outcomes. HYPOTHESIS: Decreased meniscus extrusion is associated with better clinical and radiographic outcomes compared with increased meniscus extrusion after MMPRT pullout fixation. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 39 patients who underwent MMPRT pullout fixation and had been observed for more than 5 years were recruited for this study. The mean follow-up period was 69.8 months. Participants were categorized into 2 groups according to the direction of meniscus extrusion: group A (increased extrusion; 23 patients) and group B (decreased extrusion; 16 patients). Meniscus extrusion was assessed in the coronal plane on magnetic resonance imaging preoperatively and at 1 year postoperatively. The postoperative clinical outcomes (Lysholm and International Knee Documentation Committee [IKDC] scores) and radiographic results (Kellgren Lawrence [K-L] grade and medial joint space) were compared between groups. RESULTS: Meniscus extrusion in group A increased significantly from a mean (+/ SD) of 3.5 +/- 0.9 mm preoperatively to 5.1 +/- 1.4 mm at 1 year postoperatively ( P < .001), whereas in group B, it decreased significantly from 4.1 +/- 1.3 mm preoperatively to 3.5 +/- 1.4 mm at 1 year postoperatively ( P < .001). The K-L arthritis grade (0/1/2/3/4) significantly progressed in group A (from 2/12/9/0/0 preoperatively to 0/1/14/8/0 postoperatively, respectively; P = .009) but not in group B (from 1/11/4/0/0 preoperatively to 0/6/8/2/0 postoperatively, respectively; P = .274). The mean final Lysholm and IKDC scores in group B (88.1 +/- 12.1 and 79.0 +/- 11.4, respectively) were significantly better than those in group A (81.0 +/- 9.0 and 71.1 +/- 7.8, respectively) ( P < .05). There was less medial joint space narrowing at final follow-up in group B (0.6 +/- 0.8 mm) than in group A (1.1 +/- 0.6 mm) ( P = .015). Progression of the K-L arthritis grade was seen in 50% (8/16) of the patients in group B compared with 87% (20/23) of the patients in group A ( P = .027). CONCLUSION: The current study demonstrates that in patients with MMPRTs, pullout fixation leads to favorable midterm outcomes, regardless of meniscus extrusion at 1-year follow-up. However, patients with decreased meniscus extrusion at postoperative 1 year have more favorable clinical scores and radiographic findings at midterm follow-up than those with increased extrusion at 1 year. This study indicates that one of the main goals of the repair of MMPRTs is to reduce meniscus extrusion as much as possible. PMID- 27558808 TI - A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition. AB - Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2 (phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (gamma H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased gamma-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing. PMID- 27558811 TI - Colonization by Phloem-Feeding Herbivore Overrides Effects of Plant Virus on Amino Acid Composition in Phloem of Chili Plants. AB - The 'adaptive host manipulation' hypothesis predicts that parasites can enhance their transmission rates via manipulation of their host's phenotype. For example, many plant pathogens alter the nutritional quality of their host for herbivores that serve as their vectors. However, herbivores, including non-vectors, might cause additional alterations in the plant phenotype. Here, we studied changes in the amino acid (AA) content in the phloem of chilli (Capsicum annuum) plants infected with Pepper golden mosaic virus (PepGMV) upon subsequent colonization with a non-vector, the phloem-feeding whitefly (Trialeurodes vaporariorum). Virus infection alone caused an almost 30-fold increase in overall phloem AAs, but colonization by T. vaporariorum completely reversed this effect. At the level of individual AAs, contents of proline, tyrosine, and valine increased, and histidine and alanine decreased in PepGMV -infected as compared to control plants, whereas colonization by T. vaporariorum caused decreased contents of proline, tyrosine, and valine, and increased contents of histidine and alanine. Overall, the colonization by the whitefly had much stronger effects on phloem AA composition than virus infection. We conclude that the phloem composition of a virus-infected host plant can rapidly change upon arrival of an herbivore and that these changes need to be monitored to predict the nutritional quality of the plant in the long run. PMID- 27558810 TI - Immune Intervention and Preservation of Pancreatic Beta Cell Function in Type 1 Diabetes. AB - Type 1 diabetes (T1D) results from the immune-mediated destruction of insulin producing beta cells located within the pancreatic islets of Langerhans. The autoimmune process leads to a deficiency in insulin production and resultant hyperglycemia requiring lifelong treatment with insulin administration. T1D continues to dramatically increase in incidence, especially in young children. Substantial knowledge surrounding human disease pathogenesis exists, such that T1D is now predictable with the measurement of antibodies in the peripheral blood directed against insulin and other beta cell proteins. With the ability to predict, it naturally follows that T1D should be preventable. As such, over the last two decades, numerous well-controlled clinical trials have been completed attempting to prevent diabetes onset or maintain residual beta cell function after clinical onset, all providing relatively disappointing results. Here, we review the T1D prevention efforts, the current landscape of clinical therapies, and end with a discussion regarding the future outlook for preventing T1D. PMID- 27558812 TI - DSM Criteria that Best Differentiate Intellectual Disability from Autism Spectrum Disorder. AB - Clinical characteristics of autism spectrum disorder (ASD) and intellectual disability (ID) overlap, creating potential for diagnostic confusion. Diagnostic and statistical manual of mental disorders (DSM) criteria that best differentiate children with ID and some ASD features from those with comorbid ID and ASD were identified. Records-based surveillance of ASD among 8-year-old children across 14 US populations ascertained 2816 children with ID, with or without ASD. Area under the curve (AUC) was conducted to determine discriminatory power of DSM criteria. AUC analyses indicated that restricted interests or repetitive behaviors best differentiated between the two groups. A subset of 6 criteria focused on social interactions and stereotyped behaviors was most effective at differentiating the two groups (AUC of 0.923), while communication-related criteria were least discriminatory. Matching children with appropriate treatments requires differentiation between ID and ASD. Shifting to DSM-5 may improve differentiation with decreased emphasis on language-related behaviors. PMID- 27558813 TI - Comprehensive Research on Essential Oil and Phenolic Variation in Different Foeniculum vulgare Populations During Transition from Vegetative to Reproductive Stage. AB - Chemical composition and antioxidant activity of four fennel populations (England, Spain, Poland and Iran) were investigated during six developmental stages including two vegetative and four reproductive phases. In reproductive phase, the essential oil content of fruits decreased and the maximum content (5.9%) was obtained in immediate fruits. The essential oils were analyzed using GC/MS. trans-Anethole was the main component of the leaves and the fruits oil. In leaves, it ranged from 41.28% in England at late vegetative stage to 56.6% in Poland population at early vegetative stage. Other major compounds of leaves were limonene, alpha-pinene and (Z)-beta-ocimene. In reproductive phases the trans anethole increased dramatically. It varied from 85.25% in immature fruits from Poland to 90.7% in pre-mature stage from Spain. The highest phenolic content in the extracts at different growth stages obtained 189 mg TAE/g DW at full mature stage of seed in Iran population. The flavonoid of leaves extract ranged from 3 to 7.5 mg QUE/g DW, while in fruits extract varied from 3 to 10.3 mg QUE/g DW. Antioxidant activity of the extracts was evaluated using 1,1-diphenyl-2 picrylhydrazy (DPPH) and beta-carotene model systems. Immature and full mature growth stages of fennel population from Spain indicated the highest activity in quenching of DPPH radical (74.2% and 74.5, respectively). Antioxidant activities of the extracts had high positive correlation with their phenolic contents in all fruit maturity stages. Finally, it might probably be suggested that in fennel the hot and humid condition can lead to increase trans-anethole, while the hot and dry one can produce higher amount of phenolics and flavonoids. PMID- 27558815 TI - Molecular Cell Biology of Apoptosis and Necroptosis in Cancer. AB - Cell death is a major mechanism to eliminate cells in which DNA is damaged, organelles are stressed, or oncogenes are overexpressed, all events that would otherwise predispose cells to oncogenic transformation. The pathways that initiate and execute cell death are complex, genetically encoded, and subject to significant regulation. Consequently, while these pathways are often mutated in malignancy, there is considerable interest in inducing cell death in tumor cells as therapy. This chapter addresses our current understanding of molecular mechanisms contributing to two cell death pathways, apoptotic cell death and necroptosis, a regulated form of necrotic cell death. Apoptosis can be induced by a wide variety of signals, leading to protease activation that dismantles the cell. We discuss the physiological importance of each apoptosis pathway and summarize their known roles in cancer suppression and the current efforts at targeting each pathway therapeutically. The intricate mechanistic link between death receptor-mediated apoptosis and necroptosis is described, as well as the potential opportunities for utilizing necroptosis in the treatment of malignancy. PMID- 27558814 TI - Immunogenicity of a recombinant parapoxvirus expressing the spike protein of Porcine epidemic diarrhea virus. AB - The parapoxvirus Orf virus (ORFV), has long been recognized for its immunomodulatory properties in permissive and non-permissive animal species. Here, a new recombinant ORFV expressing the full-length spike (S) protein of Porcine epidemic diarrhea virus (PEDV) was generated and its immunogenicity and protective efficacy were evaluated in pigs. The PEDV S was inserted into the ORFV121 gene locus, an immunomodulatory gene that inhibits activation of the NF kappaB signalling pathway and contributes to ORFV virulence in the natural host. The recombinant ORFV-PEDV-S virus efficiently and stably expressed the PEDV S protein in cell culture in vitro. Three intramuscular (IM) immunizations with the recombinant ORFV-PEDV-S in 3-week-old pigs elicited robust serum IgG, IgA and neutralizing antibody responses against PEDV. Additionally, IM immunization with the recombinant ORFV-PEDV-S virus protected pigs from clinical signs of porcine epidemic diarrhoea (PED) and reduced virus shedding in faeces upon challenge infection. These results demonstrate the suitability of ORFV121 gene locus as an insertion site for heterologous gene expression and delivery by ORFV-based viral vectors. Additionally, the results provide evidence of the potential of ORFV as a vaccine delivery vector for enteric viral diseases of swine. This study may have important implications for future development of ORFV-vectored vaccines for swine. PMID- 27558816 TI - Clearance of Dying Cells by Phagocytes: Mechanisms and Implications for Disease Pathogenesis. AB - The efficient clearance of apoptotic cells is an evolutionarily conserved process crucial for homeostasis in multicellular organisms. The clearance involves a series of steps that ultimately facilitates the recognition of the apoptotic cell by the phagocytes and the subsequent uptake and processing of the corpse. These steps include the phagocyte sensing of "find-me" signals released by the apoptotic cell, recognizing "eat-me" signals displayed on the apoptotic cell surface, and then intracellular signaling within the phagocyte to mediate phagocytic cup formation around the corpse and corpse internalization, and the processing of the ingested contents. The engulfment of apoptotic cells by phagocytes not only eliminates debris from tissues but also produces an anti inflammatory response that suppresses local tissue inflammation. Conversely, impaired corpse clearance can result in loss of immune tolerance and the development of various inflammation-associated disorders such as autoimmunity, atherosclerosis, and airway inflammation but can also affect cancer progression. Recent studies suggest that the clearance process can also influence antitumor immune responses. In this review, we will discuss how apoptotic cells interact with their engulfing phagocytes to generate important immune responses, and how modulation of such responses can influence pathology. PMID- 27558818 TI - Apoptotic Caspases in Promoting Cancer: Implications from Their Roles in Development and Tissue Homeostasis. AB - Apoptosis, a major form of programmed cell death, is an important mechanism to remove extra or unwanted cells during development. In tissue homeostasis apoptosis also acts as a monitoring machinery to eliminate damaged cells in response to environmental stresses. During these processes, caspases, a group of proteases, have been well defined as key drivers of cell death. However, a wealth of evidence is emerging which supports the existence of many other non-apoptotic functions of these caspases, which are essential not only in proper organism development but also in tissue homeostasis and post-injury recovery. In particular, apoptotic caspases in stress-induced dying cells can activate mitogenic signals leading to proliferation of neighbouring cells, a phenomenon termed apoptosis-induced proliferation. Apparently, such non-apoptotic functions of caspases need to be controlled and restrained in a context-dependent manner during development to prevent their detrimental effects. Intriguingly, accumulating studies suggest that cancer cells are able to utilise these functions of caspases to their advantage to enable their survival, proliferation and metastasis in order to grow and progress. This book chapter will review non apoptotic functions of the caspases in development and tissue homeostasis with focus on how these cellular processes can be hijacked by cancer cells and contribute to tumourigenesis. PMID- 27558817 TI - Microenvironmental Effects of Cell Death in Malignant Disease. AB - Although apoptosis is well recognized as a cell death program with clear anticancer roles, accumulating evidence linking apoptosis with tissue repair and regeneration indicates that its relationship with malignant disease is more complex than previously thought. Here we review how the responses of neighboring cells in the microenvironment of apoptotic tumor cells may contribute to the cell birth/cell death disequilibrium that provides the basis for cancerous tissue emergence and growth. We describe the bioactive properties of apoptotic cells and consider, in particular, how apoptosis of tumor cells can engender a range of responses including pro-oncogenic signals having proliferative, angiogenic, reparatory, and immunosuppressive features. Drawing on the parallels between wound healing, tissue regeneration and cancer, we propose the concept of the "onco-regenerative niche," a cell death-driven generic network of tissue repair and regenerative mechanisms that are hijacked in cancer. Finally, we consider how the responses to cell death in tumors can be targeted to provide more effective and long-lasting therapies. PMID- 27558819 TI - Axl and Mer Receptor Tyrosine Kinases: Distinct and Nonoverlapping Roles in Inflammation and Cancer? AB - The receptor tyrosine kinases Axl and Mer subserve the process of termination of proinflammatory signaling and have key roles in both the resolution of inflammation and restoration of homeostasis. Axl functions prominently under conditions of tissue stress or in response to infection, whereas Mer has a major role in maintenance of homeostasis within tissues. Distinct patterns of expression of Axl and Mer underlie their clearly defined functional roles during the initiation and progression of inflammation. Axl and Mer are expressed by tumor cells and by infiltrating inflammatory cells and the regulation of cellular function via Axl and Mer signaling is also important for tumorigenesis, tumor progression, and metastasis. In this review, we consider the divergent functions of Axl and Mer in the context of inflammatory processes within tumors and the implications for development of therapeutic agents targeting these receptors. PMID- 27558820 TI - Immunogenic Apoptotic Cell Death and Anticancer Immunity. AB - For many years it has been thought that apoptotic cells rapidly cleared by phagocytic cells do not trigger an immune response but rather have anti inflammatory properties. However, accumulating experimental data indicate that certain anticancer therapies can induce an immunogenic form of apoptosis associated with the emission of damage-associated molecular patterns (DAMPs), which function as adjuvants to activate host antitumor immune responses. In this review, we will first discuss recent advances and the significance of danger signaling pathways involved in the emission of DAMPs, including calreticulin, ATP, and HMGB1. We will also emphasize that switching on a particular signaling pathway depends on the immunogenic cell death stimulus. Further, we address the role of ER stress in danger signaling and the classification of immunogenic cell death inducers in relation to how ER stress is triggered. In the final part, we discuss the role of radiotherapy-induced immunogenic apoptosis and the relationship of its immunogenicity to the fraction dose and concomitant chemotherapy. PMID- 27558821 TI - Cancer Cell Death-Inducing Radiotherapy: Impact on Local Tumour Control, Tumour Cell Proliferation and Induction of Systemic Anti-tumour Immunity. AB - Radiotherapy (RT) predominantly is aimed to induce DNA damage in tumour cells that results in reduction of their clonogenicity and finally in tumour cell death. Adaptation of RT with higher single doses has become necessary and led to a more detailed view on what kind of tumour cell death is induced and which immunological consequences result from it. RT is capable of rendering tumour cells immunogenic by modifying the tumour cell phenotype and the microenvironment. Danger signals are released as well as the senescence associated secretory phenotype. This results in maturation of dendritic cells and priming of cytotoxic T cells as well as in activation of natural killer cells. However, RT on the other hand can also result in immune suppressive events including apoptosis induction and foster tumour cell proliferation. That's why RT is nowadays increasingly combined with selected immunotherapies. PMID- 27558823 TI - Killing Is Not Enough: How Apoptosis Hijacks Tumor-Associated Macrophages to Promote Cancer Progression. AB - Macrophages are a group of heterogeneous cells of the innate immune system that are crucial to the initiation, progression, and resolution of inflammation. Moreover, they control tissue homeostasis in healthy tissue and command a broad sensory arsenal to detect disturbances in tissue integrity. Macrophages possess a remarkable functional plasticity to respond to irregularities and to initiate programs that allow overcoming them in order to return back to normal. Thus, macrophages kill malignant or transformed cells, rearrange extracellular matrix, take up and recycle cellular as well as molecular debris, initiate cellular growth cascades, and favor directed migration of cells. As an example, apoptotic death of bystander cells is sensed by macrophages, initiating functional responses that support all hallmarks of cancer. In this chapter, we describe how tumor cell apoptosis hijacks tumor-associated macrophages to promote tumor growth. We propose that tumor therapy should not only kill malignant cells but also target the interaction of the host with apoptotic cancer cells, as this might be efficient to limit the protumor action of apoptotic cells and boost the antitumor potential of macrophages. Leaving the apoptotic cell/macrophage interaction untouched might also limit the benefit of conventional tumor cell apoptosis-focused therapy since surviving tumor cells might receive overwhelming support by the wound healing response that apoptotic tumor cells will trigger in local macrophages, thereby enhancing tumor recurrence. PMID- 27558822 TI - Novel Approaches to Apoptosis-Inducing Therapies. AB - Induction of apoptotic programmed cell death is one of the underlying principles of most current cancer therapies. In this review, we discuss the limitations and drawbacks of this approach and identify three distinct, but overlapping strategies to avoid these difficulties and further enhance the efficacy of apoptosis-inducing therapies. We postulate that the application of multi-targeted small molecule inhibitor cocktails will reduce the risk of the cancer cell populations developing resistance towards therapy. Following from these considerations regarding population genetics and ecology, we advocate the reconsideration of therapeutic end points to maximise the benefits, in terms of quantity and quality of life, for the patients. Finally, combining both previous points, we also suggest an altered focus on the cellular and molecular targets of therapy, i.e. targeting the (cancer cells') interaction with the tumour microenvironment. PMID- 27558824 TI - Measuring the Ability of Mice to Sense Dietary Essential Amino Acid Deficiency: The Importance of Amino Acid Status and Timing. PMID- 27558825 TI - Rapid Sensing of Dietary Amino Acid Deficiency Does Not Require GCN2. PMID- 27558826 TI - A Role for Timp3 in Microbiota-Driven Hepatic Steatosis and Metabolic Dysfunction. PMID- 27558827 TI - Industry watch: heat-not-burn tobacco products are about to reach their boiling point. PMID- 27558828 TI - The potential for LiDAR technology to map fire fuel hazard over large areas of Australian forest. AB - Fuel load is a primary determinant of fire spread in Australian forests. In east Australian forests, litter and canopy fuel loads and hence fire hazard are thought to be highest at and beyond steady-state fuel loads 15-20 years post fire. Current methods used to predict fuel loads often rely on course-scale vegetation maps and simple time-since-fire relationships which mask fine-scale processes influencing fuel loads. Here we use Light Detecting and Remote Sensing technology (LiDAR) and field surveys to quantify post-fire mid-story and crown canopy fuel accumulation and fire hazard in Dry Sclerophyll Forests of the Sydney Basin (Australia) at fine spatial-scales (20 * 20 m cell resolution). Fuel cover was quantified in three strata important for crown fire propagation (0.5-4 m, 4 15 m, >15 m) over a 144 km(2) area subject to varying fire fuel ages. Our results show that 1) LiDAR provided a precise measurement of fuel cover in each strata and a less precise but still useful predictor of surface fuels, 2) cover varied greatly within a mapped vegetation class of the same fuel age, particularly for elevated fuel, 3) time-since-fire was a poor predictor of fuel cover and crown fire hazard because fuel loads important for crown fire propagation were variable over a range of fire fuel ages between 2 and 38 years post-fire, and 4) fuel loads and fire hazard can be high in the years immediately following fire. Our results show the benefits of spatially and temporally specific in situ fuel sampling methods such as LiDAR, and are widely applicable for fire management actions which aim to decrease human and environmental losses due to wildfire. PMID- 27558829 TI - Enhanced biodegradation of PAHs by microbial consortium with different amendment and their fate in in-situ condition. AB - Microbial degradation is a useful tool to prevent chemical pollution in soil. In the present study, in-situ bioremediation of polyaromatic hydrocarbons (PAHs) by microbial consortium consisting of Serratia marcescens L-11, Streptomyces rochei PAH-13 and Phanerochaete chrysosporium VV-18 has been reported. In preliminary studies, the consortium degraded nearly 60-70% of PAHs in broth within 7 days under controlled conditions. The same consortium was evaluated for its competence under natural conditions by amending the soil with ammonium sulphate, paddy straw and compost. Highest microbial activity in terms of dehydrogenase, FDA hydrolase and aryl esterase was recorded on the 5(th) day. The degradation rate of PAHs significantly increased up to 56-98% within 7 days under in-situ however almost complete dissipation (83.50-100%) was observed on the 30(th) day. Among all the co-substrates evaluated, faster degradation of PAHs was observed in compost amended soil wherein fluorene, anthracene, phenanthrene and pyrene degraded with half-life of 1.71, 4.70, 2.04 and 6.14 days respectively. Different degradation products formed were also identified by GC-MS. Besides traces of parent PAHs eleven non-polar and five polar products were identified by direct and silylation reaction respectively. Various products formed indicated that consortium was capable to degrade PAHs by oxidation to mineralization. PMID- 27558830 TI - Embodied carbon mitigation and reduction in the built environment - What does the evidence say? AB - Of all industrial sectors, the built environment puts the most pressure on the natural environment, and in spite of significant efforts the International Energy Agency suggests that buildings-related emissions are on track to double by 2050. Whilst operational energy efficiency continues to receive significant attention by researchers, a less well-researched area is the assessment of embodied carbon in the built environment in order to understand where the greatest opportunities for its mitigation and reduction lie. This article approaches the body of academic knowledge on strategies to tackle embodied carbon (EC) and uses a systematic review of the available evidence to answer the following research question: how should we mitigate and reduce EC in the built environment? 102 journal articles have been reviewed systematically in the fields of embodied carbon mitigation and reduction, and life cycle assessment. In total, 17 mitigation strategies have been identified from within the existing literature which have been discussed through a meta-analysis on available data. Results reveal that no single mitigation strategy alone seems able to tackle the problem; rather, a pluralistic approach is necessary. The use of materials with lower EC, better design, an increased reuse of EC-intensive materials, and stronger policy drivers all emerged as key elements for a quicker transition to a low carbon built environment. The meta-analysis on 77 LCAs also shows an extremely incomplete and short-sighted approach to life cycle studies. Most studies only assess the manufacturing stages, often completely overlooking impacts occurring during the occupancy stage and at the end of life of the building. The LCA research community have the responsibility to address such shortcomings and work towards more complete and meaningful assessments. PMID- 27558831 TI - Influence of pH and ozone dose on sulfaquinoxaline ozonation. AB - Sulfaquinoxaline (SQX) is an antimicrobial of the sulfonamides class. Usually employed in veterinary medicine, this contaminant of emerging concern has been found in superficial and groundwater and its consequences for the environment and human health are not completely known. In this study, SQX (C0 = 500 MUg L-1, 1 L) degradation by an ozonation process at pH 3, 7, and 11 was evaluated. Ozonation was effective in degrading SQX: efficiency exceeding 99% was obtained applying an ozone dose of 2.8 mg L-1 at pH 3. Assays were performed according to a 22 design of experiments (DOE) with star points and three central points for statistical validity. Minimum and maximum levels were set at 3 and 11 for pH, and 0 and 11.5 mg L-1 for applied ozone dose. There was no significant interaction between these variables, and the pH value played the most important role in terms of contaminant degradation. In relation to toxicity, samples ozonated at pH 3 did not inhibit the luminescence of the bacteria, even though different intermediates were formed and identified by mass spectra. At pH 7, inhibition of luminescence remained almost constant (at around 30%) according to ozonation time or ozone dose. However, the hydroxyl radical, the major oxidant at pH 11, was responsible for the formation of toxic intermediates. PMID- 27558832 TI - AMPK<->Sirt1: From a signaling network to a combination drug. PMID- 27558833 TI - Invasion of moso bamboo into a Japanese cedar plantation affects the chemical composition and humification of soil organic matter. AB - Bamboo, which has dense culms and root rhizome systems, can alter soil properties when it invades adjacent forests. Therefore, this study investigated whether bamboo invasions can cause changes in soil organic matter (SOM) composition and soil humification. We combined solid-state (13)C NMR spectroscopy and chemical analysis to examine the SOM in a Japanese cedar (Cryptomeria japonica) and adjacent bamboo (Phyllostachys edulis) plantation. Bamboo reduced soil organic C (SOC) content, compared to the cedar plantation. The value of ?logK (ratio of absorbance of humic acids at 400 and 600 nm) was cedar > transition zone > bamboo soils. Our results indicated that bamboo increased SOM humification, which could be due to the fast decomposition of bamboo litter with the high labile C. Furthermore, intensive management in the bamboo plantation could enhance the humification as well. Overall, litter type can control an ecosystem's SOC nature, as reflected by the finding that higher labile C in bamboo litter contributed the higher ratios of labile C to SOC and lower ratios of recalcitrant C to SOC in bamboo soils compared with cedar soils. The invasion of bamboo into the Japanese cedar plantation accelerated the degradation of SOM. PMID- 27558834 TI - Datathons and Software to Promote Reproducible Research. AB - BACKGROUND: Datathons facilitate collaboration between clinicians, statisticians, and data scientists in order to answer important clinical questions. Previous datathons have resulted in numerous publications of interest to the critical care community and serve as a viable model for interdisciplinary collaboration. OBJECTIVE: We report on an open-source software called Chatto that was created by members of our group, in the context of the second international Critical Care Datathon, held in September 2015. METHODS: Datathon participants formed teams to discuss potential research questions and the methods required to address them. They were provided with the Chatto suite of tools to facilitate their teamwork. Each multidisciplinary team spent the next 2 days with clinicians working alongside data scientists to write code, extract and analyze data, and reformulate their queries in real time as needed. All projects were then presented on the last day of the datathon to a panel of judges that consisted of clinicians and scientists. RESULTS: Use of Chatto was particularly effective in the datathon setting, enabling teams to reduce the time spent configuring their research environments to just a few minutes-a process that would normally take hours to days. Chatto continued to serve as a useful research tool after the conclusion of the datathon. CONCLUSIONS: This suite of tools fulfills two purposes: (1) facilitation of interdisciplinary teamwork through archiving and version control of datasets, analytical code, and team discussions, and (2) advancement of research reproducibility by functioning postpublication as an online environment in which independent investigators can rerun or modify analyses with relative ease. With the introduction of Chatto, we hope to solve a variety of challenges presented by collaborative data mining projects while improving research reproducibility. PMID- 27558835 TI - Impact of cardiovascular risk factor control on long-term cardiovascular and all cause mortality in the general population. AB - PURPOSE: In clinical trials, lowering cardiovascular risk factors (CVRFs) reduces cardiovascular (CV) morbidity and mortality. We assessed the impact of controlling CVRFs at baseline on long-term all-cause and CV mortality in the general population. METHODS: Analysis was based on the Third French MONICA population-based survey (1994-1997). Vital status was obtained 18 years after inclusion. Statistical analysis was based on Cox-modelling. RESULTS: About 3402 participants aged 35-64 were included and 569 (17%) presented with 2 or more uncontrolled CVRFs, 1194 (35%) had one uncontrolled CVRF, 770 (23%) had all CVRFs controlled under treatment (or were former smokers) and 869 (25%) exhibited no CVRF. During the follow-up, 389 deaths occurred (76 were due to CV causes). Considering all-cause mortality, the adjusted hazard ratios (aHR) for subjects with one uncontrolled CVRF and for those with two or more were 1.38 [1.03-1.83] (p = 0.029) and 1.80 [1.33-2.43](p < 0.001), respectively, as compared with subjects presenting with all their CVRFs controlled. For subjects exhibiting no CVRF, the aHR was 0.66 [0.44-0.98] (p = 0.042). Considering CV mortality, aHRs for subjects presenting with one and two or more uncontrolled CVRF were 1.70 [0.84-3.42] (p = 0.138) and 3.67 [1.85-7.29] (p < 0.001), respectively, as compared with subjects who had either all their CVRFs controlled or exhibited no CVRF. CONCLUSIONS: Failing to control CVRFs significantly increases long-term all cause and CV mortality in the French general population. Key messages Only 30% of patients with cardiovascular risk factors were controlled. Failing to control cardiovascular risk factors significantly increased long-term cardiovascular and all-cause mortality. A residual risk for all-cause mortality remained even when patients were controlled. PMID- 27558836 TI - Erratum. PMID- 27558837 TI - Efficient and transgene-free genome editing in wheat through transient expression of CRISPR/Cas9 DNA or RNA. AB - Editing plant genomes is technically challenging in hard-to-transform plants and usually involves transgenic intermediates, which causes regulatory concerns. Here we report two simple and efficient genome-editing methods in which plants are regenerated from callus cells transiently expressing CRISPR/Cas9 introduced as DNA or RNA. This transient expression-based genome-editing system is highly efficient and specific for producing transgene-free and homozygous wheat mutants in the T0 generation. We demonstrate our protocol to edit genes in hexaploid bread wheat and tetraploid durum wheat, and show that we are able to generate mutants with no detectable transgenes. Our methods may be applicable to other plant species, thus offering the potential to accelerate basic and applied plant genome-engineering research. PMID- 27558838 TI - Shiga toxin glycosphingolipid receptors and their lipid membrane ensemble in primary human blood-brain barrier endothelial cells. AB - Shiga toxin (Stx)-mediated injury to microvascular endothelial cells in the brain significantly contributes to the pathogenesis of the hemolytic-uremic syndrome caused by enterohemorrhagic Escherichia coli (EHEC). Stxs are AB5 toxins and the B-pentamers of the two major Stx subtypes Stx1a and Stx2a preferentially bind to the glycosphingolipid (GSL) globotriaosylceramide (Gb3Cer) expressed by human endothelial cells. Here we report on comprehensive structural analysis of the different lipoforms of Gb3Cer (Galalpha4Galbeta4Glcbeta1Cer) and globotetraosylceramide (Gb4Cer, GalNAcbeta3Galalpha4Galbeta4Glcbeta1Cer, the less effective Stx receptor) of primary human brain microvascular endothelial cells and their association with lipid rafts. Detergent-resistant membranes (DRMs), obtained by sucrose density gradient ultracentrifugation, were used as lipid raft analogous microdomains of the liquid-ordered phase and nonDRM fractions were employed as equivalents for the liquid-disordered phase of cell membranes. Structures of the prevalent lipoforms of Gb3Cer and Gb4Cer were those with Cer (d18:1, C16:0), Cer (d18:1, C22:0) and Cer (d18:1, C24:1/C24:0) determined by electrospray ionization mass spectrometry that was combined with thin-layer chromatography immunodetection using anti-Gb3Cer and anti-Gb4Cer antibodies as well as Stx1a and Stx2a subtypes. Association of Stx receptor GSLs was determined by co-localization with lipid raft-specific membrane protein flotillin-2 and canonical lipid raft marker sphingomyelin with Cer (d18:1, C16:0) and Cer (d18:1, C24:1/C24:0) in the liquid-ordered phase, whereas lyso-phosphatidylcholine was detectable exclusively in the liquid-disordered phase. Defining the precise microdomain structures of primary endothelial cells may help to unravel the initial mechanisms by which Stxs interact with their target cells and will help to develop novel preventive and therapeutic measures for EHEC-mediated diseases. PMID- 27558839 TI - Hyaluronan synthase control of synthesis rate and hyaluronan product size are independent functions differentially affected by mutations in a conserved tandem B-X7-B motif. AB - Hyaluronan synthases (HAS) normally make large (>MDa) hyaluronan (HA) products. Smaller HA fragments (e.g. 100-400 kDa) produced in vivo are associated with inflammation and cell signaling by HA receptors that bind small, but not large, HA. Although HA fragments can arise from breakdown by hyaluronidases, HAS might also be regulated directly to synthesize small HA. Here we examined the Streptococcus equisimilis HAS (SeHAS) C-terminus, which contains a tandem B-X7-B motif (K398-X7-R406-X7-K414), by testing the effects of 27 site-specific scanning mutations and 7 C-terminal truncations on HA synthesis activity and weight average mass. Although HAS enzymes cannot be HA-binding proteins, these motifs are highly conserved within the Class I HAS family. Fifteen Arg406 mutants made large MDa HA (86-110% wildtype size), with specific activities from 70% to 177% of wildtype. In contrast, 10 of 12 Lys398 mutants made HA that was 8-14% of wildtype size (<=250-480 kDa), with specific activities from 14% to 64% of wildtype. Four nearly inactive (2% wildtype activity) C-terminal truncation mutants made MDa HA (56-71% wildtype). The results confirm earlier findings with Cys-mutants [Weigel PH, Baggenstoss BA. 2012. Hyaluronan synthase polymerizing activity and control of product size are discrete enzyme functions that can be uncoupled by mutagenesis of conserved cysteines. Glycobiology 22:1302-1310] that HAS uses two independent activities to control HA size and HA synthesis rate; these are two separate functions. We conclude that HAS regulatory modifications that alter tandem B-X7-B motif conformation could mimic these mutagenesis-induced effects, allowing HAS in vivo to make small HA directly. The results also support a model in which the tandem-motif region is part of the intra-HAS pore and interacts directly with HA. PMID- 27558840 TI - High-resolution crystal structures of Colocasia esculenta tarin lectin. AB - Tarin, the Colocasia esculenta lectin from the superfamily of alpha-d-mannose specific plant bulb lectins, is a tetramer of 47 kDa composed of two heterodimers. Each heterodimer possesses homologous monomers of ~11.9 (A chain) and ~12.7 (B chain) kDa. The structures of apo and carbohydrate-bound tarin were solved to 1.7 A and 1.91 A, respectively. Each tarin monomer forms a canonical beta-prism II fold, common to all members of Galanthus nivalis agglutinin (GNA) family, which is partially stabilized by a disulfide bond and a conserved hydrophobic core. The heterodimer is formed through domain swapping involving the C-terminal beta-strand and the beta-sheet on face I of the prism. The tetramer is assembled through the dimerization of the B chains from heterodimers involving face II of each prism. The 1.91 A crystal structure of tarin bound to Manalpha(1,3)Manalpha(1,6)Man reveals an expanded carbohydrate-binding sequence (QxDxNxVxYx4/6WX) on face III of the beta-prism. Both monomers possess a similar fold, except for the length of the loop, which begins after the conserved tyrosine and creates the binding pocket for the alpha(1,6)-terminal mannose. This loop differs in size and amino-acid composition from 10 other beta-prism II domain proteins, and may confer carbohydrate-binding specificity among members of the GNA-related lectin family. PMID- 27558842 TI - Characterization of Low-Strigolactone Germplasm in Pea (Pisum sativum L.) Resistant to Crenate Broomrape (Orobanche crenata Forsk.). AB - Crenate broomrape (Orobanche crenata Forsk.) is a devastating parasitic weed threatening the cultivation of legumes around the Mediterranean and in the Middle East. So far, only moderate levels of resistance were reported to occur in pea (Pisum sativum L.) natural germplasm, and most commercial cultivars are prone to severe infestation. Here, we describe the selection of a pea line highly resistant to O. crenata, following the screening of local genetic resources. Time series observations show that delayed emergence of the parasite is an important parameter associated with broomrape resistance. High performance liquid chromatography connected to tandem mass spectrometry analysis and in vitro broomrape germination bioassays suggest that the resistance mechanism might involve the reduced secretion of strigolactones, plant hormones exuded by roots and acting as signaling molecules for the germination of parasitic weeds. Two years of replicated trials in noninfested fields indicate that the resistance is devoid of pleiotropic effects on yield, in contrast to pea experimental mutants impaired in strigolactone biosynthesis and, thus, is suitable for use in breeding programs. PMID- 27558843 TI - miRNAs Regulate hERG. AB - BACKGROUND: The human ether-a-go-go-related gene (hERG) is the major molecular component of the rapidly activating delayed rectifier K+ current (Ikr ). Impairment of hERG function is believed to be a mechanism causing long-QT syndromes (LQTS). Growing evidences have shown that microRNAs (miRNAs) are involved in functional modulation of the hERG pathway. The purpose of this study was to screen and validate miRNAs that regulate the hERG pathway. The miRNAs identified in this study will provide new tools to assess the mechanism of LQTS. METHODS: Six miRNAs were selected by algorithm predictions based on potential interaction with hERG. The effects of each miRNA on hERG were assessed by use of the Dual-Luciferase Reporter assay system, qRT-PCR, Western blotting, and confocal fluorescence microscopy. Furthermore, whole-cell patch clamp technique was used to validate the effect of miR-103a-1 on the electrophysiological characteristic of the Ikr of the hERG protein channel. RESULTS: miR-134, miR-103a 1, miR-143, and miR-3619 significantly downregulated luciferase activity (P < 0.05) in a reporter test system. These 4 miRNAs significantly suppressed expression of hERG mRNA and protein in U2OS cells (P < 0.05).Corresponding AMOs rescued expression of hERG mRNA and protein. Confocal microscopy showed that all 4 miRNAs reduced the expression of both immature and mature hERG protein. miR 103a-1 decreased the maximum current and tail current amplitudes of hERG channel. CONCLUSIONS: Expression and functions of hERG are regulated by specific miRNAs. PMID- 27558845 TI - Divergent Synthesis of Hydro-gamma-Carbolines and Multisubstituted Indoles through Grob Fragmentation/Mannich Cyclization. AB - A distinct strategy for the divergent synthesis of hydro-gamma-carbolines and multisubstituted indoles is reported. The stereochemical outcomes and a control experiment indicate that the reactions likely proceed through Grob fragmentation/Mannich cyclization rather than a concerted aza-pinacol rearrangement. PMID- 27558846 TI - Perseverance and parents of children with complex: Unsung heroes. PMID- 27558847 TI - Anaesthetic efficacy of intraligamentary injection techniques on mandibular molars diagnosed with asymptomatic irreversible pulpitis: A retrospective study. AB - The objective of this study was to evaluate the success rate of intraligamentary injections (ILI) using a two- or four-site injection technique. One hundred and fifty-one mandibular molars diagnosed with asymptomatic irreversible pulpitis received ILI at the mesiobuccal and distobuccal aspects of the roots. Patients who experienced pain when the access cavity was performed received additional supplemental ILI in the mesiolingual and distolingual aspects. Pulpal anaesthesia was considered successful when complete analgesia was achieved. The data were analysed by means of the Fisher's exact and Pearson's chi-square tests. IL anaesthesia was successful for 92.1% of the teeth. Forty-eight teeth (31.8%) were sufficiently anaesthetised using the two-site ILI and 91 teeth (60.3%) following supplemental IL anaesthesia in two more sites. The results of this study indicate that the use of four-site IL injections as a primary anaesthetic technique may be considered a favourable alternative to the common IANB. PMID- 27558844 TI - Single-point single-molecule FRAP distinguishes inner and outer nuclear membrane protein distribution. AB - The normal distribution of nuclear envelope transmembrane proteins (NETs) is disrupted in several human diseases. NETs are synthesized on the endoplasmic reticulum and then transported from the outer nuclear membrane (ONM) to the inner nuclear membrane (INM). Quantitative determination of the distribution of NETs on the ONM and INM is limited in available approaches, which moreover provide no information about translocation rates in the two membranes. Here we demonstrate a single-point single-molecule FRAP microscopy technique that enables determination of distribution and translocation rates for NETs in vivo. PMID- 27558848 TI - sNebula, a network-based algorithm to predict binding between human leukocyte antigens and peptides. AB - Understanding the binding between human leukocyte antigens (HLAs) and peptides is important to understand the functioning of the immune system. Since it is time consuming and costly to measure the binding between large numbers of HLAs and peptides, computational methods including machine learning models and network approaches have been developed to predict HLA-peptide binding. However, there are several limitations for the existing methods. We developed a network-based algorithm called sNebula to address these limitations. We curated qualitative Class I HLA-peptide binding data and demonstrated the prediction performance of sNebula on this dataset using leave-one-out cross-validation and five-fold cross validations. This algorithm can predict not only peptides of different lengths and different types of HLAs, but also the peptides or HLAs that have no existing binding data. We believe sNebula is an effective method to predict HLA-peptide binding and thus improve our understanding of the immune system. PMID- 27558849 TI - Distinct roles of the two VPS33 proteins in the endolysosomal system in Caenorhabditis elegans. AB - Sec1/Munc-18 (SM) family proteins are essential regulators in intracellular transport in eukaryotic cells. The SM protein Vps33 functions as a core subunit of two tethering complexes, class C core vacuole/endosome tethering (CORVET) and homotypic fusion and vacuole protein sorting (HOPS) in the endocytic pathway in yeast. Metazoan cells possess two Vps33 proteins, VPS33A and VPS33B, but their precise roles remain unknown. Here, we present a comparative analysis of Caenorhabditis elegans null mutants for these proteins. We found that the vps 33.1 (VPS33A) mutants exhibited severe defects in both endocytic function and endolysosomal biogenesis in scavenger cells. Furthermore, vps-33.1 mutations caused endocytosis defects in other tissues, and the loss of maternal and zygotic VPS-33.1 resulted in embryonic lethality. By contrast, vps-33.2 mutants were viable but sterile, with terminally arrested spermatocytes. The spermatogenesis phenotype suggests that VPS33.2 is involved in the formation of a sperm-specific organelle. The endocytosis defect in the vps-33.1 mutant was not restored by the expression of VPS-33.2, which indicates that these proteins have nonredundant functions. Together, our data suggest that VPS-33.1 shares most of the general functions of yeast Vps33 in terms of tethering complexes in the endolysosomal system, whereas VPS-33.2 has tissue/organelle specific functions in C. elegans. PMID- 27558850 TI - Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry. AB - Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies-either where volunteers are infected with a disease or where existing cases are recruited-in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens-influenza and norovirus-as well as Ebola virus disease. PMID- 27558851 TI - On the evolutionary advantage of multi-cusped teeth. AB - A hallmark of mammalian evolution is a progressive complexity in postcanine tooth morphology. However, the driving force for this complexity remains unclear: whether to expand the versatility in diet source, or to bolster tooth structural integrity. In this study, we take a quantitative approach to this question by examining the roles of number, position and height of multiple cusps in determining sustainable bite forces. Our approach is to use an extended finite element methodology with due provision for step-by-step growth of an embedded crack to determine how fracture progresses with increasing occlusal load. We argue that multi-cusp postcanine teeth are well configured to withstand high bite forces provided that multiple cusps are contacted simultaneously to share the load. However, contact on a single near-wall cusp diminishes the strength. Location of the load points and cusp height, rather than cusp number or radius, are principal governing factors. Given these findings, we conclude that while complex tooth structures can enhance durability, increases in cusp number are more likely to be driven by the demands of food manipulation. Structural integrity of complex teeth is maintained when individual cusps remain sufficiently distant from the side walls and do not become excessively tall relative to tooth width. PMID- 27558852 TI - Correction to 'Physical limits on bacterial navigation in dynamic environments'. PMID- 27558854 TI - Low-Dose Aripiprazole Augmentation in Amitriptyline-Resistant Burning Mouth Syndrome: Results from Two Cases. PMID- 27558856 TI - Cancer Seeding Risk from an Epidural Blood Patch in Patients with Leukemia or Lymphoma. AB - Introduction: Lumber punctures are a common procedure in patients with cancer. However, a potential complication of a lumbar puncture is a postdural puncture headache. The risk of neoplastic seeding to the central nervous system has led to concern over performing epidural blood patches (EBPs) for the treatment of postdural puncture headaches in patients with cancer. The goal of this retrospective study was to evaluate cancer seeding in the central nervous system in patients diagnosed with leukemia or lymphoma. Methods: Institutional electronic records were queried over a 13-year period from 2000 to 2013 for patients with leukemia and/or lymphoma and who received at least one EBP. Demographic and procedural data, cancer treatments, and mortality were all examined. Patient records were reviewed for evidence of new-onset neoplastic central nervous system seeding after an epidural blood patch. Results: A total of 80 patients were identified for review. Eighteen patients had a diagnosis of leukemia, and 62 had lymphoma. Following an EBP, none of the patients experienced new cancer or cancer seeding in the central nervous system following an epidural blood patch at a median follow-up of 3.74 years. Discussion: Though the risks of EBP in the cancer patient population have been hypothesized, no previous studies have assessed the risk of seeding cancer to the central nervous system. Based on our results, an epidural blood patch bears low risk of cancer seeding when used to treat postdural puncture headache that is unresponsive to conservative treatments. PMID- 27558855 TI - Cuff Algometry for Estimation of Hyperalgesia and Pain Summation. AB - Objective: Cuff algometry is useful to assess pain sensitivity mechanisms, but effects of cuff position and stimulation pattern are not clear. Methods: In 20 healthy volunteers, cuff pain detection threshold (PDT) and pain tolerance (PTT) were recorded with cuffs accommodating two individual chambers at four locations (eight positions) along the leg, using ramp inflation (1 kPa/s) until subjects indicated PDT and PTT. Repeated stimulations (1-s stimulation, 4-s break) with a staircase increase in stimulus intensity (5 kPa/step) were used to assess PDT and PTT on a single location. Spatial pain summation was calculated as the ratio between PTTs recorded with one chamber or simultaneously with two neighbor chambers. Temporal pain summation was assessed by repeated cuff stimulations (1-s stimulation, 1-s break) and the pain intensity was recorded on a visual analog scale (VAS); the PTT from ramp and staircase assessments were used as stimulus intensity. Results: For the most distal cuff position, the PTT was higher compared with other leg positions except when in proximity to the knee ( P < 0.01). The PDT was higher for the distal part compared with the mid-portions of the lower and upper leg ( P < 0.01). Compared with other leg locations, the spatial summation ratio was highest at the proximal lower leg ( P < 0.02). The staircase versus ramp pattern revealed higher PDT and PTT (P < 0.01), as well as pronounced temporal pain summation ( P < 0.01). Conclusion: The mid-portion of the lower leg is recommended for cuff placement, and the staircase paradigm provides relevant stimulus intensity for assessment of temporal pain summation. PMID- 27558853 TI - Progress, pitfalls and parallel universes: a history of insect phylogenetics. AB - The phylogeny of insects has been both extensively studied and vigorously debated for over a century. A relatively accurate deep phylogeny had been produced by 1904. It was not substantially improved in topology until recently when phylogenomics settled many long-standing controversies. Intervening advances came instead through methodological improvement. Early molecular phylogenetic studies (1985-2005), dominated by a few genes, provided datasets that were too small to resolve controversial phylogenetic problems. Adding to the lack of consensus, this period was characterized by a polarization of philosophies, with individuals belonging to either parsimony or maximum-likelihood camps; each largely ignoring the insights of the other. The result was an unfortunate detour in which the few perceived phylogenetic revolutions published by both sides of the philosophical divide were probably erroneous. The size of datasets has been growing exponentially since the mid-1980s accompanied by a wave of confidence that all relationships will soon be known. However, large datasets create new challenges, and a large number of genes does not guarantee reliable results. If history is a guide, then the quality of conclusions will be determined by an improved understanding of both molecular and morphological evolution, and not simply the number of genes analysed. PMID- 27558857 TI - Survey of Primary Care and Mental Health Prescribers' Perspectives on Reducing Opioid and Benzodiazepine Co-Prescribing Among Veterans. AB - Background: Due to the involvement of opioids and benzodiazepines in rising pharmaceutical overdoses, a reduction in coprescribing of these medications is a national priority, particularly among patients with substance use disorders and other high-risk conditions. However, little is known about primary care (PC) and mental health (MH) prescribers' perspectives on these medications and efforts being implemented to reduce coprescribing. Design: An anonymous survey. Setting: One multisite VA health care system. Subjects: Participants were 55 PC and 31 MH prescribers. Methods: Survey development was guided by the Promoting Action on Research Implementation in Health Services (PARIHS) conceptual framework. PC and MH prescribers of opioids or benzodiazepines were invited to complete an anonymous electronic survey. Responses were collapsed to highlight agreement, disagreement, and neutrality and summarized with means and percentages. Results: Over 80% of both prescriber groups reported concern about concurrent use and > 75% strongly agreed with clinical practice guidelines (CPG) that recommend caution in coprescribing among patients with high-risk conditions. More than 40% of both prescriber groups indicated that coprescribing continues because of beliefs that patients appear stable without adverse events and tapering/discontinuation is too difficult. Over 70% of prescribers rated strategies for addressing patients who refuse to discontinue, more time with patients, and identification of high-risk patients as helpful in reducing coprescribing. Conclusion: Despite strong agreement with CPGs, prescribers reported several barriers that contribute to coprescribing of opioids and benzodiazepines and challenge their ability to taper these medications. Multiple interventions are likely needed to reduce opioid and benzodiazepine coprescribing. PMID- 27558859 TI - Effects of Maydis stigma polysaccharide on the intestinal microflora in type-2 diabetes. AB - CONTEXT: Diabetes is a serious endocrine and metabolic disorder. Food supplements attract people's attention in mitigating health problems from the aspect of gastrointestinal microflora. Maydis stigma (Zea mays subsp. mays L. [Poaceae]), has been used as water decoction for treating diabetes in folk medicine. It has great potential, and feasibly a stable form of Maydis stigma commercial products could be developed to fulfil the health food market. OBJECTIVE: To study the effects of Maydis stigma polysaccharide (MSP) on the intestinal microflora in type-2 diabetes (T2D). MATERIALS AND METHODS: MSP was fractioned from Maydis stigma by distilled water, purified by DEAE-52 Cellulose chromatography and Sephadex G-200 gel column. Streptozotocin (160 mg/kg) was intraperitoneal injected for 3 days to build model. The diabetic mice were randomly divided into five groups together with control group (10 mice in each group). The doses of MSP were 400, 600 and 800 mg/kg, respectively. After 5 weeks of administration, antidiabetic effects and intestinal microflora balance restoring activities were evaluated by denaturing gradient gel electrophoresis. RESULTS: Blood glucose levels of MSP-treated groups showed extremely significant hypoglycemic effects (p < 0.01), body weight increased showed extremely significant (p < 0.01) differences. Bacteroides, Lactobacillus and Prevotella were dominant organisms in the intestinal tract. The quality and quantity of Lactobacillus and Bacteroides genus increased remarkably with increasing concentration of MSP. DISCUSSION AND CONCLUSION: Experimental results of this study suggest that MSP has the significant potential to be used as a natural agent for treating T2D and restoring the intestinal microflora balance. PMID- 27558858 TI - Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study. AB - BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. FINDINGS: We identified three types of treatment response trajectories: 'gradual responders' (GR; 3576 patients, 91.7%) had a baseline mean DAS28 of 4.1 and progressive improvement over time; 'rapid responders' (RR; 219 patients, 5.6%) had higher baseline DAS28 and rapid improvement in disease activity; 'inadequate responders' (IR; 103 patients, 2.6%) had high DAS28 at baseline (5.1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p=0.03), and EULAR good or moderate responses at 1year was much higher among 'rapid responders' (p<0.001). INTERPRETATION: Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation. PMID- 27558861 TI - The "Seven Pillars" Response to Patient Safety Incidents: Effects on Medical Liability Processes and Outcomes. AB - OBJECTIVE: To determine whether a communication and resolution approach to patient harm is associated with changes in medical liability processes and outcomes. DATA SOURCES/STUDY SETTING: Administrative, safety, and risk management data from the University of Illinois Hospital and Health Sciences System, from 2002 to 2014. STUDY DESIGN: Single health system, interrupted time series design. Using Mann-Whitney U tests and segmented regression models, we compared means and trends in incident reports, claims, event analyses, patient communication consults, legal fees, costs per claim, settlements, and self-insurance expenses before and after the implementation of the "Seven Pillars" communication and resolution intervention. DATA COLLECTION METHODS: Queried databases maintained by Department of Safety and Risk Management and the Department of Administrative Services at UIH. Extracted data from risk module of the Midas incident reporting system. PRINCIPAL FINDINGS: The intervention nearly doubled the number of incident reports, halved the number of claims, and reduced legal fees and costs as well as total costs per claim, settlement amounts, and self-insurance costs. CONCLUSIONS: A communication and optimal resolution (CANDOR) approach to adverse events was associated with long-lasting, clinically and financially significant changes in a large set of core medical liability process and outcome measures. PMID- 27558864 TI - Effects of concanavalin A on the progesterone production by bovine steroidogenic luteal cells in vitro. AB - The aim of this study was to evaluate the effects of concanavalin A (CONA) on the progesterone (P4) production by bovine steroidogenic luteal cells (LCs) in vitro. Luteal cells were collected during the mid-luteal stage (at 10-12 days following ovulation) and processed in the laboratory. Luteal cells were grown for 7 days in a humid atmosphere with 5% CO2 , with or without 10% foetal bovine serum, and were subjected to the following treatments: control: no treatment; CONA (10 MUg/ml); LH (100 MUg/ml); CONA + LH; LH (100 MUg/ml) + prostaglandin F2alpha (PGF2alpha) (10 ng/ml); CONA + LH + PGF2alpha. Samples of the culture media were collected on days 1 (D1) and 7 (D7) for P4 quantification. The cells were counted on D7 of culture. Differences between treatments were considered statistically significant at p < .05. Culture in the presence of CONA decreased the P4 secreting capacity of LCs on D7 of culture, particularly in the absence of serum. The cell numbers did not change between treatments. PMID- 27558865 TI - Sixth nerve palsy following botulinum toxin injection for facial rejuvenation. AB - BACKGROUND: Botulinum toxin A (BTX) has been widely used for a variety of facial esthetic procedures within the last couple of decades. Efficacy and safety of BTX for facial rejuvenation has been extensively studied in multiple randomized prospective controlled trials. Focal weakness is among the most commonly reported adverse effects. Adverse reactions tend to occur most commonly due to errors in dosing formulation and errors with the techniques of the application. No serious long-term complications have been reported. MAIN OBSERVATION: We present the case of a 52-year-old female presenting with diplopia one week following the injection of BTX for facial rejuvenation at glabella, forehead and crow's feet areas. CONCLUSIONS: Injection of BTX adjacent to periorbital area may be associated with extra-ocular muscle paralysis. PMID- 27558862 TI - Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer's disease model. AB - Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer's disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Abeta peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Abeta-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD. PMID- 27558867 TI - Construction of Epidermal Growth Factor Receptor Peptide Magnetic Nanovesicles with Lipid Bilayers for Enhanced Capture of Liver Cancer Circulating Tumor Cells. AB - Highly effective targeted tumor recognition via vectors is crucial for cancer detection. In contrast to antibodies and proteins, peptides are direct targeting ligands with a low molecular weight. In the present study, a peptide magnetic nanovector platform containing a lipid bilayer was designed using a peptide amphiphile (PA) as a skeleton material in a controlled manner without surface modification. Fluorescein isothiocyanate-labeled epidermal growth factor receptor (EGFR) peptide nanoparticles (NPs) could specifically bind to EGFR-positive liver tumor cells. EGFR peptide magnetic vesicles (EPMVs) could efficiently recognize and separate hepatoma carcinoma cells from cell solutions and treated blood samples (ratio of magnetic EPMVs versus anti-EpCAM NPs: 3.5 +/- 0.29). Analysis of the circulating tumor cell (CTC) count in blood samples from 32 patients with liver cancer showed that EPMVs could be effectively applied for CTC capture. Thus, this nanoscale, targeted cargo-packaging technology may be useful for designing cancer diagnostic systems. PMID- 27558868 TI - Bruxism is a continuously distributed behaviour, but disorder decisions are dichotomous (Response to letter by Manfredini, De Laat, Winocur, & Ahlberg (2016)). PMID- 27558866 TI - An S-warfarin and AZD1981 interaction: in vitro and clinical pilot data suggest the N-deacetylated amino acid metabolite as the primary perpetrator. AB - AIM: AZD1981 is an orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist progressed to phase II trials for the treatment of allergic asthma. Previously performed in vitro human hepatocyte incubations identified N-deacetylated AZD1981 as a primary metabolite. We report on metabolite exposure from a clinical excretion balance, on in vitro studies performed to determine the likelihood of a metabolite dependent drug-drug interaction (DDI) and on a clinical warfarin DDI study. The aim was to demonstrate that N-deacetylated AZD1981 is responsible for the observed interaction. METHODS: The excretion and biotransformation of [14 C] AZD1981 were studied in healthy male volunteers, and subsequently in vitro cytochrome P450 (CYP) inhibition and hepatocyte uptake investigations were carried out with metabolites and the parent drug. A clinical DDI study using coadministered twice-daily 100 mg and 400 mg AZD1981 with 25 mg warfarin was performed. RESULTS: The excretion balance study showed N-deacetylated AZD1981 to be the most abundant metabolite present in plasma. In vitro data revealed the metabolite to be a weak CYP2C9 time-dependent inhibitor, subject to more active hepatic uptake than the parent molecule. Clinically, the S-warfarin area under the plasma concentration-time curve increased, on average, 1.4-fold [95% confidence interval (CI) 1.22, 1.50] and 2.4-fold (95% CI 2.11, 2.64) after 100 mg (n = 13) and 400 mg (n = 11) AZD1981 administration, respectively. In vitro CYP inhibition and hepatocyte uptake data were used to explain the interaction. CONCLUSIONS: N-deacetylated AZD1981 can be added to the small list of drug metabolites reported as sole contributors to clinical drug-drug interactions, with weak time-dependent inhibition exacerbated by efficient hepatic uptake being the cause. PMID- 27558870 TI - Chapter 3 - Compression therapy. PMID- 27558869 TI - Trends and Correlates of Disparities in Alcohol-Related Mortality Between Hispanics and Non-Hispanic Whites in the United States, 1999 to 2014. AB - BACKGROUND: Among Hispanics, chronic liver disease and cirrhosis are among the leading causes of death despite generally lower alcohol consumption rates. Moreover, recent national studies have suggested temporal changes in Hispanic consumption and alcohol mortality, which raises the question of whether Hispanic white disparities in alcohol-related mortality are also changing over time. This study aimed to describe temporal trends of alcohol-related mortality between Hispanics and non-Hispanic (NH) whites in the United States from 1999 to 2014 and to assess county-level sociodemographic characteristics that are associated with racial/ethnic disparities in age-adjusted alcohol-related mortality. METHODS: We conducted a population-based, cross-sectional, ecologic study using multiple cause-of-death mortality data linked, at the county level, to census data from the American Community Survey. RESULTS: Overall, 77% of alcohol-related deaths were among men, and Hispanic men had the highest age-adjusted alcohol-related mortality rate (41.6 per 100,000), followed by NH white men (34.8), NH white women (10.8), and Hispanic women (6.7). Whereas the relative gap in alcohol related mortality between NH white and Hispanic women increased from 1999 to 2014, the disparity between NH white and Hispanic men that was pronounced in earlier years was eliminated by 2012. From 2007 to 2014, when the race/ethnic disparity among men was decreasing, county-specific Hispanic:NH white age adjusted mortality ratios (AAMRs) ranged from 0.29 to 2.64. Lower Hispanic rates were associated with large metropolitan counties, and those counties that tended to have Hispanic populations were less acculturated, as evidenced by their higher rates of being foreign-born, non-U.S. citizens or citizens through naturalization, and a higher proportion that do not speak English "very well." CONCLUSIONS: Since 1999, whereas the increasing mortality rate among whites is leading to a widening gap among women, mortality differences between Hispanic and white men have been eliminated. The understanding of contextual factors that are associated with disparities in alcohol-related mortality may assist in tailoring prevention efforts that meet the needs of minority populations. PMID- 27558841 TI - Biological roles of glycans. AB - Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences. PMID- 27558872 TI - WALKING THE TIGHTROPE: THE COMMITTEE ON THE BEHAVIORAL SCIENCES AND ACADEMIC CULTURES AT THE UNIVERSITY OF CHICAGO, 1949-1955. AB - The Chicago Committee on the Behavioral Sciences occupies a special place in the eponymous movement. Involving prominent figures such as psychologist James G. Miller and neurophysiologist Ralph W. Gerard, this committee embodied the common belief among behavioral scientists that a cross-disciplinary approach using natural science methods was key to understanding major issues facing mid-century American society. This interdivisional committee fell under the jurisdiction of both the natural and social sciences. As such, its flagship project, an institute of mental sciences, had to face the reluctance both of natural scientists who thought it inadequately scientific and of social scientists who regard its efforts as too narrow in scope and too biological in orientation. Though it failed in its main objective to create an institute, the committee was a formidable instrument of intellectual stimulation and socialization for its members. It provided them with an opportunity to familiarize themselves with each other's scientific backgrounds, practices and jargons, realize the significance of academic cultural differences and learn ways to accommodate them. PMID- 27558871 TI - High-throughput method for the quantitation of metabolites and co-factors from homocysteine-methionine cycle for nutritional status assessment. AB - AIM: There is increasing interest in the profiling and quantitation of methionine pathway metabolites for health management research. Currently, several analytical approaches are required to cover metabolites and co-factors. RESULTS: We report the development and the validation of a method for the simultaneous detection and quantitation of 13 metabolites in red blood cells. The method, validated in a cohort of healthy human volunteers, shows a high level of accuracy and reproducibility. CONCLUSION: This high-throughput protocol provides a robust coverage of central metabolites and co-factors in one single analysis and in a high-throughput fashion. In large-scale clinical settings, the use of such an approach will significantly advance the field of nutritional research in health and disease. PMID- 27558874 TI - Erratum: Percolation-based precursors of transitions in extended systems. PMID- 27558873 TI - Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells. AB - Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-alpha/beta receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNbeta in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID- 27558875 TI - Pulmonary exposure to cellulose nanocrystals caused deleterious effects to reproductive system in male mice. AB - Over the past several years there has been an increased number of applications of cellulosic materials in many sectors, including the food industry, cosmetics, and pharmaceuticals. However, to date, there are few studies investigating the potential adverse effects of cellulose nanocrystals (CNC). The objective of this study was to determine long-term outcomes on the male reproductive system of mice upon repeated pharyngeal aspiration exposure to CNC. To achieve this, cauda epididymal sperm samples were analyzed for sperm concentration, motility, morphological abnormalities, and DNA damage. Testicular and epididymal oxidative damage was evaluated, as well as histopathology examination of testes. In addition, changes in levels of testosterone in testes and serum and of luteinizing hormone (LH) in serum were determined. Three months after the last administration, CNC exposure significantly altered sperm concentration, motility, cell morphology, and sperm DNA integrity. These parameters correlated with elevated proinflammatory cytokines levels and myeloperoxidase (MPO) activity in testes, as well as oxidative stress in both testes and epididymis. Exposure to CNC also produced damage to testicular structure, as evidenced by presence of interstitial edema, frequent dystrophic seminiferous tubules with arrested spermatogenesis and degenerating spermatocytes, and imbalance in levels of testosterone and LH. Taken together, these results demonstrate that pulmonary exposure to CNC induces sustained adverse effects in spermatocytes/spermatozoa, suggesting male reproductive toxicity. PMID- 27558876 TI - Flagship umbrella species needed for the conservation of overlooked aquatic biodiversity. PMID- 27558879 TI - mGluR2/3 mediates short-term control of nicotine-seeking by acute systemic N acetylcysteine. AB - Chronic self-administration of nicotine induces maladaptive changes in the cortico-accumbal glutamate (Glu) network. Consequently, re-exposure to nicotine associated cues raises extracellular Glu in the nucleus accumbens reinstating drug-seeking. Restoring basal concentrations of extracellular Glu, thereby increasing tonic activation of the presynaptic group II metabotropic Glu receptors (mGluR2/3) with N-acetylcysteine (N-AC), might offer a valid therapeutic approach for maintaining smoking abstinence. Although N-AC modulates nicotine-seeking behavior by drug-associated stimuli in abstinent rats, it is still unclear whether it occurs through activation of mGluR2/3. Male Wistar rats were trained to associate discriminative stimuli (SD s) with the availability of intravenous nicotine (0.03 mg/kg/65 ul/2-second/infusion) or oral saccharin (100 ul of 50 mg/l) self-administration versus non-reward. Reinforced response was followed by a cue signaling 20-second time-out (CSs). Once the training criterion was met, rats underwent lever press extinction, without reinforcers, SD s and CSs. Re-exposure to nicotine or saccharin SD+ /CS+ , but not non-reward SD- /CS- , revived responding on the previously reinforced lever. Acute N-AC, 100 but not 60 or 30 mg/kg i.p., reduced cue-induced nicotine-seeking. N-AC 100 mg/kg did not modify cue-induced saccharin-seeking behavior or influenced locomotor activity. Blocking mGluR2/3 with the selective antagonist LY341495, 1 mg/kg i.p., completely prevented the antirelapse activity of N-AC. The finding that N-AC prevents cue-induced nicotine-seeking by stimulating mGluR2/3 might indicate a therapeutic opportunity for acute cue-controlled nicotine-seeking. Future studies could evaluate the persistent effects of chronic N-AC in promoting enduring suppression of nicotine-cue conditioned responding. PMID- 27558878 TI - Chemical Probes to Directly Profile Palmitoleoylation of Proteins. AB - Palmitoleoylation is a unique fatty acylation of proteins in which a monounsaturated fatty acid, palmitoleic acid (C16:1), is covalently attached to a protein. Wnt proteins are known to be palmitoleoylated by cis-Delta9 palmitoleate at conserved serine residues. O-palmitoleoylation plays a critical role in regulating Wnt secretion, binding to the receptors, and in the dynamics of Wnt signaling. Therefore, protein palmitoleoylation is important in tissue homeostasis and tumorigenesis. Chemical probes based on saturated fatty acids, such as omega-alkynyl palmitic acid (Alk-14 or Alk-C16 ), have been used to study Wnt palmitoleoylation. However, such probes require prior conversion to the unsaturated fatty acid by stearoyl-CoA desaturase (SCD) in cells, significantly decreasing their selectivity and efficiency for studying protein palmitoleoylation. We synthesized and characterized omega-alkynyl cis- and trans palmitoleic acids (cis- and trans-Alk-14:1) as chemical probes to directly study protein palmitoleoylation. We found that cis-Alk-14:1 could more efficiently label Wnt proteins in cells. Interestingly, the DHHC family of palmitoyl acyltransferases can charge both saturated and unsaturated fatty acids, potentially using both as acyl donors in protein palmitoylation and palmitoleoylation. Furthermore, proteomic analysis of targets labeled by these probes revealed new cis- and trans-palmitoleoylated proteins. Our studies provided new chemical tools and revealed new insights into palmitoleoylation in cell signaling. PMID- 27558880 TI - Allylic Alkylations with Enamine Nucleophiles. AB - Allylic alkylation reactions are some of the most important carbon-carbon bond forming reactions in organic synthesis. In particular, the alkylation of carbonyl substrates provides an efficient pathway to structurally diverse molecules. Such reactions predominantly rely on the in situ generation of a nucleophilic enamine intermediate. This brief personal account describes research carried out in our group concerning the Pd-catalyzed allylic alkylation of carbonyl compounds using these species. Our methodology combines Pd-catalysis with metallocene ligands to carry out these transformations. PMID- 27558877 TI - Pleiotropic action of CpG-ODN on endothelium and macrophages attenuates angiogenesis through distinct pathways. AB - There is an integral relationship between vascular cells and leukocytes in supporting healthy tissue homeostasis. Furthermore, activation of these two cellular components is key for tissue repair following injury. Toll-like receptors (TLRs) play a role in innate immunity defending the organism against infection, but their contribution to angiogenesis remains unclear. Here we used synthetic TLR9 agonists, cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN), to investigate the role of TLR9 in vascular pathophysiology and identify potential therapeutic translation. We demonstrate that CpG-ODN stimulates inflammation yet inhibits angiogenesis. Regulation of angiogenesis by CpG-ODN is pervasive and tissue non-specific. Further, we noted that synthetic CpG-ODN requires backbone phosphorothioate but not TLR9 activation to render and maintain endothelial stalk cells quiescent. CpG-ODN pre-treated endothelial cells enhance macrophage migration but restrain pericyte mobilisation. CpG-ODN attenuation of angiogenesis, however, remains TLR9-dependent, as inhibition is lost in TLR9 deficient mice. Additionally, CpG-ODNs induce an M1 macrophage phenotype that restricts angiogenesis. The effects mediated by CpG-ODNs can therefore modulate both endothelial cells and macrophages through distinct pathways, providing potential therapeutic application in ocular vascular disease. PMID- 27558881 TI - Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta analysis. AB - An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78-90%; the pooled specificity was 93% with a 95% CI of 90-95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD. PMID- 27558882 TI - Renin-Angiotensin System Control for Chronic Kidney Disease Patients Undergoing Coronary Surgery. AB - PURPOSE: We investigated the effectiveness of active renin-angiotensin aldosterone system (RAAS) control with human atrial natriuretic peptide (hANP) and an angiotensin II receptor blocker (ARB) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass grafting (CABG). METHODS: A total of 286 consecutive patients with CKD undergoing CABG were divided into three groups: Group C (n = 50) receiving placebo, the hANP group (n = 60) receiving hANP, and the active RAAS control therapy (ARC) group (n = 56) receiving hANP plus an ARB. Renal function, brain natriuretic peptide (BNP) and RAAS parameters were analyzed. RESULTS: After 1 year, renal function parameters were better in the hANP and ARC groups compared with group C, and the dialysis rate was significantly lower (group C: 12%, hANP group: 1.7%, ARC group: 1.8%, p = 0.018) in the hANP and ARC groups. BNP levels were significantly lower in the hANP and ARC groups compared with group C (p = 0.001). There was also a significant difference of aldosterone among the groups (p = 0.023), as well as a significant difference between group C and the ARC group (p = 0.017). CONCLUSIONS: The present study showed that active RAAS control preserved renal function in patients with CKD undergoing CABG. The improved early postoperative outcome with RAAS control may lead to long-term inhibition of cardiovascular events. PMID- 27558884 TI - Development of polymeric irinotecan nanoparticles using a novel lactone preservation strategy. AB - Irinotecan (IRT) is an important part of the first- and second-line regimen for metastatic colorectal and some other cancers. However, IRT suffers the constraints of pH-dependent conversion of active lactone form to inactive carboxylate form, burst release owing to its aqueous solubility, short half-life and dose-dependent side effects. In this study, we developed polymeric nanoparticles (NPs) that not only deliver IRT to tumor sites, but also overcome its drawbacks by preserving active lactone conformation, prolonging the plasma circulation time, and by providing sustained release. IRT complex was rendered hydrophobic by ion-pairing with anions (docusate sodium, sodium lauryl sulfate, and sodium tripolyphosphate), and loaded in PEG-PLGA NPs via water/oil/water double emulsification method. The NPs were spherical, ~60nm, monodispersed, and had shell-core morphology. They retained >80% lactone form for more than 1 month of storage and exhibited sustained release characteristics. In addition, sub 100nm size of NPs offered elevated cellular internalization. Owing to the presence of hydrophilic PEG outer layer and drug-loaded hydrophobic PLGA core, NPs conferred excellent plasma stability and prolonged the retention time of IRT by more than 10-fold as compared to free IRT. Therefore, this system could provide an excellent platform for efficient and sustained delivery of IRT and similar labile drugs to the tumor site, while maintaining their chemical integrity. PMID- 27558883 TI - The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel. AB - BACKGROUND: Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous and endogenous stress signals including noxious temperature. However, the role of heat shock proteins in nociception remains poorly understood. We carried out an expression analysis of the constitutively expressed 70 kDa heat-shock cognate protein, a member of the stress-induced HSP70 family in lumbar dorsal root ganglia from a mouse model of Complete Freund's Adjuvant-induced chronic inflammatory pain. We used immunolabeling of dorsal root ganglion neurons, behavioral analysis and patch clamp electrophysiology in both dorsal root ganglion neurons and HEK cells transfected with Hsc70 and Transient Receptor Potential Channels to examine their functional interaction in heat shock stress condition. RESULTS: We report an increase in protein levels of Hsc70 in mouse dorsal root ganglia, 3 days post Complete Freund's Adjuvant injection in the hind paw. Immunostaining of Hsc70 was observed in most of the dorsal root ganglion neurons, including the small size nociceptors immunoreactive to the TRPV1 channel. Standard whole-cell patch-clamp technique was used to record Transient Receptor Potential Vanilloid type 1 current after exposure to heat shock. We found that capsaicin-evoked currents are inhibited by heat shock in dorsal root ganglion neurons and transfected HEK cells expressing Hsc70 and TRPV1. Blocking Hsc70 with matrine or spergualin compounds prevented heat shock-induced inhibition of the channel. We also found that, in contrast to TRPV1, both the cold sensor channels TRPA1 and TRPM8 were unresponsive to heat shock stress. Finally, we show that inhibition of TRPV1 depends on the ATPase activity of Hsc70 and involves the rho-associated protein kinase. CONCLUSIONS: Our work identified Hsc70 and its ATPase activity as a central cofactor of TRPV1 channel function and points to the role of this stress protein in pain associated with neurodegenerative and/or metabolic disorders, including aging. PMID- 27558885 TI - Higher FT4 or TSH below the normal range are associated with increased risk of dementia: a meta-analysis of 11 studies. AB - Observational studies of thyroid function and dementia have reported conflicting results. We reviewed cohort and case-control studies from MEDLINE, EMBASE, Web of Science and the Cochrane Library that focused on the association between serum thyroxine, thyrotropin and dementia. A total of 24,952 participants from three case-control and eight cohort studies were included. The relationships between dementia and the per standard deviation (SD) increment of free thyroxine (FT4) (random relative ratio (RR) = 1.08, 95% confidence interval (CI) 1.00-1.17) and thyroid-stimulating hormone (TSH) (fixed RR = 0.91, 95% CI 0.84-0.99) were well established. TSH levels in the low category were associated with an increased risk of dementia (fixed RR = 1.60, 95% CI 1.27-2.00). However, the positive association was confined to TSH levels below the normal range (fixed RR = 1.77, 95% CI 1.31-2.39), not those in the lower tertile of the normal range (fixed RR = 1.39, 95% CI 0.98-1.97). Additionally, dementia was not significantly associated with high TSH levels (fixed RR = 0.99, 95% CI 0.76-1.29). Furthermore, there was no positive association between dementia and the low or high categories of TSH in men. Thus, individuals with higher FT4 levels or those with TSH levels below the normal range have an increased risk of dementia. PMID- 27558886 TI - Impact of area regeneration policies: performing integral interventions, changing opportunity structures and reducing health inequalities. AB - BACKGROUND: Urban regeneration policies are area-based interventions addressing multidimensional problems. In this study, we analyse the impact of urban regeneration processes on the evolution of inequalities in mortality from certain causes. On the basis of Fundamental Cause Theory (FCT), our main hypothesis is that the impact of urban regeneration programmes will be more clearly observed on the causes of preventable deaths, as these programmes imply a direct or indirect improvement to a whole range of 'flexible resources' that residents in relevant areas have access to, and which ultimately may influence the inverse relationship between socioeconomic status and health. METHODS: Using a quasi-experimental design and data from Longitudinal Statistics on Survival and Longevity of Andalusia (Spain), we analyse differences in the evolution of standard mortality ratios for preventable and less-preventable causes of premature death. This encompasses 59 neighbourhoods in 37 municipalities where urban regeneration projects were implemented in the last decade within the framework of three different programmes and in 59 counterparts where these policies were not implemented. RESULTS: As expected in line with FCT, there are no significant patterns in the evolution of internal differences in terms of less-preventable mortality. However, excessive preventable mortality strongly decreases in the neighbourhoods with intervention programmes, specifically in those where two or more projects were in force. This is even more apparent for women. CONCLUSIONS: The urban regeneration policies studied seem to contribute to reducing health inequity when the interventions are more integral in nature. PMID- 27558887 TI - Mechanistic insights into the vascular effects of blueberries: Evidence from recent studies. AB - Cardiovascular disease is the leading cause of death in the United States. Dietary habits influence a variety of cardiovascular complications such as peripheral artery disease, heart failure, and kidney disease. We along with others have previously reported the cardiovascular beneficial effects of dietary flavonoids. Anthocyanins, one class of flavonoids widely available in berries, have recently drawn wide scientific attention because of their diverse health benefits. Epidemiological, clinical, and animal studies indicate that blueberry anthocyanins exert protection against cardiovascular complications by acting on multiple targets in the vascular system. These include activating endothelial nitric oxide synthase signaling, reducing oxidative stress, improving inflammatory pathways, and ameliorating dyslipidemia. Anthocyanins are extensively metabolized in humans suggesting that their vascular benefits are likely mediated by their circulating metabolites. However, the bioactivities of blueberry metabolites are unknown. Evaluating the bioactivities of metabolites, analyzing their structure-activity relationship, and well-designed human trials are needed to understand the potential vascular effects of blueberries and their metabolites. Understanding the vascular effects will provide a solid scientific foundation to recommend blueberries to improve vascular health. This review highlights the recent developments in the understanding of the vascular effects of blueberries with special emphasis on the molecular mechanisms involved. PMID- 27558888 TI - Perceived difficulty and success rate of landmark- vs ultrasonography-guided lumbar punctures in a novice study group: a randomized crossover trial. PMID- 27558889 TI - Poplar woody taproot under bending stress: the asymmetric response of the convex and concave sides. AB - BACKGROUND AND AIMS: Progress has been made in understanding the physiological and molecular basis of root response to mechanical stress, especially in the model plant Arabidopsis thaliana, in which bending causes the initiation of lateral root primordia toward the convex side of the bent root. In the case of woody roots, it has been reported that mechanical stress induces an asymmetric distribution of lateral roots and reaction wood formation, but the mechanisms underlying these responses are largely unknown. In the present work, the hypothesis was tested that bending could determine an asymmetric response in the two sides of the main root axis as cells are stretched on the convex side and compressed on the concave side. METHODS: Woody taproots of 20 seedlings were bent to an angle of 90 degrees using a steel net. Changes in the anatomy, lignin and phytohormone content and proteome expression in the two sides of the bent root were analysed; anatomical changes, including dissimilarities and similarities to those found in poplar bent woody stem, were also considered. KEY RESULTS: Compression forces at the concave side of poplar root induced the formation of reaction wood which presented a high lignin content and was associated with the induction of cambium cell activity. Auxin seemed to be the main hormone triggering lignin deposition and cell wall strengthening in the concave sides. Abscisic acid appeared to function in the water stress response induced by xylem structures and/or osmotic alterations in the compression sides, whereas gibberellins may control cell elongation and gravitropisms. CONCLUSIONS: Poplar root reaction wood showed characteristics different from those produced in bent stem. Besides providing biomechanical functions, a bent root ensures water uptake and transport in the deforming condition induced by tension and compression forces by two different strategies: an increase in xylem thickness in the compressed side, and lateral root formation in the tension side. PMID- 27558890 TI - Atypical teratoid/rhabdoid tumours: clinicopathological characteristics, prognostic factors and outcomes of 22 children from 2010 to 2015 in China. AB - Atypical teratoid/rhabdoid tumours (AT/RTs) are rare, highly malignant tumours of the central nervous system (CNS) with poor prognosis that usually affect young children. The aim of this study was to assess the clinicopathological features and prognostic factors of AT/RTs. Here, we describe the clinicopathological and immunohistochemical characteristics, along with the treatments and outcomes, of 22 patients with AT/RTs treated in our hospital from 2010 to 2015. Morphologically, cytoplasmic vacuoles, the most common characteristic in our cases, were observed in 68% of the cases. Similarly, vesicular nuclei were detected in 68% of the cases. However, rhabdoid cells were found in only 59.1% of the cases and were not observed in 40.9% of the cases. Immunohistochemical analysis revealed loss of nuclear INI1 expression in all 22 cases. Age, surgical resection and adjuvant therapy, but not tumour location, were associated with AT/RTs patient prognosis. Our results showed that cells with cytoplasmic vacuoles or with vesicular nuclei are more common than rhabdoid cells in patients with AT/RTs and that a lack of INI1 protein expression is the most useful marker for the differential diagnosis of AT/RTs. Young age is a negative prognostic factor, whereas gross total surgical resection and adjuvant therapy are positive prognostic factors for AT/RT patients. PMID- 27558891 TI - Genotyping of herpes simplex virus type 1 by whole-genome sequencing. AB - A previous phylogenetic analysis based on 32 full-length sequences of herpes simplex virus type 1 (HSV-1) suggested three major phylogenetic groups (phylogroups) with distinct geographic distribution: (1) western strains from Europe and North America, (2) isolates from Asia and one American strain and (3) isolates from Africa only. Here, we sequenced the genomes of additional 10 clinical HSV-1 isolates from Germany, and subsequently compared these sequences to 40 published HSV-1 genomes. The present data demonstrate that HSV-1 is the most diverse human alphaherpesvirus (mean pairwise p-distance of 0.756 %) and confirm the tripartite tree. However, as the German isolates cluster with strains of both phylogroups I and II, it is demonstrated that the latter is also present in Europe and thus is a Eurasian phylogroup. Tree-order scans indicate that HSV-1 evolution is massively influenced by recombination including all investigated strains regardless of the areal distribution of the phylogroups. Numerous recombination events in the evolution of HSV-1 may also influence genotyping as the present HSV-1 genotyping schemes do not yield results consistent with phylogroup classification. Genotyping of HSV-1 is currently based on analyses of intragenic sequence polymorphisms of US2, glycoprotein G (gG, US4) and gI (US7). Each of the 10 German HSV-1 isolates displayed a different US2/gG/gI-genotype combination, but clustered either in phylogroup I or II. In conclusion, the phylogroup concept provides a HSV-1 typing scheme that largely reflects human migration history, whereas the analysis of single-nucleotide polymorphisms fails to render significant biological properties, but allows description of individual genetic traits. PMID- 27558892 TI - A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans. AB - Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir 231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes. PMID- 27558894 TI - Letter to the editorResponse to: Russo A, Capogrosso P, La Croce G, et al. Serenoa repens, selenium and lycopene to manage lower urinary tract symptoms suggestive for benign prostatic hyperplasia. Expert Opin Drug Saf. 2016 Jun;1:1 10. PMID- 27558893 TI - Gamification and Adherence to Web-Based Mental Health Interventions: A Systematic Review. AB - BACKGROUND: Adherence to effective Web-based interventions for common mental disorders (CMDs) and well-being remains a critical issue, with clear potential to increase effectiveness. Continued identification and examination of "active" technological components within Web-based interventions has been called for. Gamification is the use of game design elements and features in nongame contexts. Health and lifestyle interventions have implemented a variety of game features in their design in an effort to encourage engagement and increase program adherence. The potential influence of gamification on program adherence has not been examined in the context of Web-based interventions designed to manage CMDs and well-being. OBJECTIVE: This study seeks to review the literature to examine whether gaming features predict or influence reported rates of program adherence in Web-based interventions designed to manage CMDs and well-being. METHODS: A systematic review was conducted of peer-reviewed randomized controlled trials (RCTs) designed to manage CMDs or well-being and incorporated gamification features. Seven electronic databases were searched. RESULTS: A total of 61 RCTs met the inclusion criteria and 47 different intervention programs were identified. The majority were designed to manage depression using cognitive behavioral therapy. Eight of 10 popular gamification features reviewed were in use. The majority of studies utilized only one gamification feature (n=58) with a maximum of three features. The most commonly used feature was story/theme. Levels and game leaders were not used in this context. No studies explicitly examined the role of gamification features on program adherence. Usage data were not commonly reported. Interventions intended to be 10 weeks in duration had higher mean adherence than those intended to be 6 or 8 weeks in duration. CONCLUSIONS: Gamification features have been incorporated into the design of interventions designed to treat CMD and well-being. Further research is needed to improve understanding of gamification features on adherence and engagement in order to inform the design of future Web-based health interventions in which adherence to treatment is of concern. Conclusions were limited by varied reporting of adherence and usage data. PMID- 27558896 TI - Corrigendum. PMID- 27558895 TI - Association of shift-work, daytime napping, and nighttime sleep with cancer incidence and cancer-caused mortality in Dongfeng-tongji cohort study. AB - BACKGROUND: Few studies investigated the combined effects of night-shift work, daytime napping, and nighttime sleep on cancer incidence and mortality. METHODS: A total of 25,377 participants were included in this study. Information on sleep habits, cancer incidences, and mortalities were collected. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HRs, 95%CIs). RESULTS: Male subjects experienced >=20 years of night-shift work, or without daytime napping had an increased risk of cancer, when compared with males who did not have night-shift work or napped for 1-30 min [HR (95%CI) = 1.27 (1.01-1.59) and 2.03 (1.01-4.13), respectively]. Nighttime sleep for >=10 h was associated with a separate 40% and 59% increased risk of cancer [HR (95%CI) = 1.40 (1.04-1.88)] and cancer-caused mortality [HR (95%CI) = 1.59 (1.01-2.49)] than sleep for 7-8 h/night. Combined effects of three sleep habits were further identified. Male participants with at least two above risk sleep habits had a 43% increased risk of cancer [HR (95%CI) = 1.43 (1.07-2.01)] and a 2.07-fold increased cancer-caused mortality [HR (95%CI) = 2.07 (1.25-3.29)] than those who did not have any above risk sleep habits. However, no significant associations were observed among women. CONCLUSIONS: Long night-shift work history, without daytime napping, and long nighttime sleep duration were independently and jointly associated with higher cancer incidence among males. KEY MESSAGES Night-shift work of >=20 years, without napping, and nighttime sleep of >=10 h were associated with increased cancer incidence. Nighttime sleep >=10 h was associated with a 2.07-fold increased cancer-caused mortality among males. Combined effects of night-shift work >=20 years, without napping, and nighttime sleep >=10 h on increasing cancer incidence were existed among males. PMID- 27558897 TI - YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4 NOT deadenylase complex. AB - Methylation at the N6 position of adenosine (m(6)A) is the most abundant RNA modification within protein-coding and long noncoding RNAs in eukaryotes and is a reversible process with important biological functions. YT521-B homology domain family (YTHDF) proteins are the readers of m(6)A, the binding of which results in the alteration of the translation efficiency and stability of m(6)A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m(6)A-containing RNAs is poorly understood. Here we report that m(6)A-containing RNAs exhibit accelerated deadenylation that is mediated by the CCR4-NOT deadenylase complex. We further show that YTHDF2 recruits the CCR4-NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and that this recruitment is essential for the deadenylation of m(6)A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m(6)A-containing RNAs in mammalian cells. PMID- 27558898 TI - Sources of resistance and susceptibility to Septoria tritici blotch of wheat. AB - An association genetics analysis was conducted to investigate the genetics of resistance to Septoria tritici blotch, caused by the fungus Zymoseptoria tritici (alternatively Mycosphaerella graminicola), in cultivars and breeding lines of wheat (Triticum aestivum) used in the UK between 1860 and 2000. The population was tested with Diversity Array Technology (DArT) and simple-sequence repeat (SSR or microsatellite) markers. The lines formed a single population with no evidence for subdivision, because there were several common ancestors of large parts of the pedigree. Quantitative trait loci (QTLs) controlling Septoria resistance were postulated on 11 chromosomes, but 38% of variation was not explained by the identified QTLs. Calculation of best linear unbiased predictions (BLUPs) identified lineages of spring and winter wheat carrying different alleles for resistance and susceptibility. Abundant variation in Septoria resistance may be exploited by crossing well-adapted cultivars in different lineages to achieve transgressive segregation and thus breed for potentially durable quantitative resistance, whereas phenotypic selection for polygenic quantitative resistance should be effective in breeding cultivars with increased resistance. The most potent allele reducing susceptibility to Septoria, on chromosome arm 6AL, was associated with reduced leaf size. Genes which increase susceptibility to Septoria may have been introduced inadvertently into UK wheat breeding programmes from cultivars used to increase yield, rust resistance and eyespot resistance between the 1950s and 1980s. This indicates the need to consider trade-offs in plant breeding when numerous traits are important and to be cautious about the use of non-adapted germplasm. PMID- 27558899 TI - Investigating asthma comorbidities: a systematic scoping review protocol. AB - INTRODUCTION: Asthma is a common long-term disorder with a number of related comorbid conditions, which may affect asthma outcomes. There is a need for greater appreciation for understanding how these comorbidities interact with asthma in order to improve asthma outcomes. OBJECTIVES: To systematically identify and map out key asthma comorbidities. METHODS: We will systematically search the following electronic databases: MEDLINE, EMBASE, ISI Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and Google Scholar. Additional literature will be identified by searching the reference list of identified eligible studies and by searching the repositories of international conference proceedings, including ISI Conference Proceeding Citation Index, and ZETOC (British Library). DISSEMINATION: The findings from this systematic scoping review will be reported at scientific meetings and published in a peer-reviewed journal. PMID- 27558900 TI - Demographic and socioeconomic inequalities in the risk of emergency hospital admission for violence: cross-sectional analysis of a national database in Wales. AB - OBJECTIVES: To investigate the risk of emergency hospital admissions for violence (EHAV) associated with demographic and socioeconomic factors in Wales between 2007/2008 and 2013/2014, and to describe the site of injury causing admission. DESIGN: Database analysis of 7 years' hospital admissions using the Patient Episode Database for Wales (PEDW). SETTING AND PARTICIPANTS: Wales, UK, successive annual populations ~2.8 million aged 0-74 years. PRIMARY OUTCOME: The first emergency admission for violence in each year of the study, defined by the International Classification of Diseases V.10 (ICD-10) codes for assaults (X85 X99, Y00-Y09) in any coding position. RESULTS: A total of 11 033 admissions for assault. The majority of admissions resulted from head injuries. The overall crude admission rate declined over the study period, from 69.9 per 100 000 to 43.2 per 100 000, with the largest decrease in the most deprived quintile of deprivation. A generalised linear count model with a negative binomial log link, adjusted for year, age group, gender, deprivation quintile and settlement type, showed the relative risk was highest in age group 18-19 years (RR=6.75, 95% CI 5.88 to 7.75) compared with the reference category aged 10-14 years. The risk decreased with age after 25 years. Risk of admission was substantially higher in males (RR=4.55, 95% CI 4.31 to 4.81), for residents of the most deprived areas of Wales (RR=3.60, 95% CI 3.32 to 3.90) compared with the least deprived, and higher in cities (RR=1.37, 95% CI 1.27 to 1.49) and towns (RR=1.32, 95% CI 1.21 to 1.45) compared with villages. CONCLUSIONS: Despite identifying a narrowing in the gap between prevalence of violence in richer and poorer communities, violence remains strongly associated with young men living in areas of socioeconomic deprivation. There is potential for a greater reduction, given that violence is mostly preventable. Recommendations for reducing inequalities in the risk of admission for violence are discussed. PMID- 27558901 TI - OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain. Trial protocol. AB - INTRODUCTION: Low back pain and neck pain are extremely prevalent and are responsible for an enormous burden of disease globally. Strong analgesics, such as opioid analgesics, are recommended by clinical guidelines for people with acute low back pain or neck pain who are slow to recover and require more pain relief. Opioid analgesics are widely and increasingly used, but there are no strong efficacy data supporting the use of opioid analgesics for acute low back pain or neck pain. Concerns regarding opioid use are further heightened by the risks of adverse events, some of which can be serious (eg, dependency, misuse and overdose). METHODS AND ANALYSIS: OPAL is a randomised, placebo-controlled, triple blinded trial that will investigate the judicious use of an opioid analgesic in 346 participants with acute low back pain and/or neck pain who are slow to recover. Participants will be recruited from general practice and randomised to receive the opioid analgesic (controlled release oxycodone plus naloxone up to 20 mg per day) or placebo in addition to guideline-based care (eg, reassurance and advice of staying active) for up to 6 weeks. Participants will be followed-up for 3 months for effectiveness outcomes. The primary outcome will be pain severity. Secondary outcomes will include physical functioning and time to recovery. Medication-related adverse events will be assessed and a cost-effectiveness analysis will be conducted. We will additionally assess long-term use and risk of misuse of opioid analgesics for up to 12 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained. Trial results will be disseminated by publications and conference presentations, and via the media. TRIAL REGISTRATION NUMBER: ACTRN12615000775516: Pre-results. PMID- 27558902 TI - Methods for a longitudinal cohort of refugee children in a regional community in Australia. AB - PURPOSE: Few studies explore the long-term health and well-being of refugee children. A longitudinal cohort of refugee children was created to determine health and well-being outcomes over time. This article describes the methodology used to conduct this study, including sample characteristics and effectiveness of recruitment and retention strategies. PARTICIPANTS: Newly arrived refugee children settling in a regional part of Australia aged 6 months to 15 years were recruited between 2009 and 2013 and 85% were followed for an average of 31 months. METHOD AND DESIGN: General practitioners conducted health and pathology examinations shortly after arrival. Additional follow-up assessments were conducted by the research team at an average of 13 months after arrival for the first (year 2) and 31 months for the second (year 3) assessment. Children under 5 years had developmental and children aged 4-17 years had social-emotional screening. Families were assessed for risk and protective factors using a structured interview and the Social Readjustment Ratings Scale. Parent experience of the research was explored. FINDINGS TO DATE: Eligibility criteria were met by 158 of 228 (69%) newly arrived children, 61 of whom (39%) were enrolled. Retention was 100% (n=61) at year 2 and 85% at year 3. The study sample was younger than and had an over-representation of African refugees as compared to the eligible population. Parents reported that the research was respectful. FUTURE PLANS: This study demonstrates that a longitudinal cohort study in refugee children is feasible and acceptable, and retention rates can be high. The establishment of this cohort provides the opportunity to analyse valuable data about the early settlement experience, risk and protective factors and long-term health and well-being outcomes in refugee children. These are necessary to identify refugee children in need of additional support and to guide future service delivery. PMID- 27558904 TI - Is the incidence of heart attack still decreasing in Australia? Developing reliable methods for monitoring trends in myocardial infarction and coronary heart disease (AUS-MOCHA): a study protocol. AB - INTRODUCTION: Accurate monitoring of acute coronary heart disease (CHD) is essential for understanding the effects of primary and secondary prevention and for planning of healthcare services. The ability to reliably monitor acute CHD has been affected by new diagnostic tests for myocardial infarction (MI) and changing clinical classifications and management of CHD. Our study will develop new and reliable methods for monitoring population trends in incidence, outcomes and health service usage for acute CHD and chest pain. METHODS AND ANALYSIS: The study cohort of all CHD will be identified from the Western Australian Data Linkage System using state-wide data sets for emergency department presentation, hospitalisations and mortality data for 2002-2014. This core linked data set will be supplemented with data from hospital medical record reviews, pathology data and hospital pharmacy dispensing databases. The consistency over time of the coding of the different subgroups of CHD/chest pain (ST-elevation MI, non-ST elevation MI, unstable angina, stable angina, other CHD, non-CHD chest pain) in linked data will be assessed using these data sources, and an algorithm developed detailing groups in which temporal trends can be reliably measured. This algorithm will be used for measurement of trends in incidence and outcomes of acute CHD, and to develop further methods for monitoring acute CHD using unlinked and linked data with varying availability of hospitalisation history. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Human Research Ethics Committees of the WA Department of Health (#2016/23) and The University of Western Australia (RA/4/1/7230). Findings will be disseminated via publication in peer-reviewed journals, and presentation at national and international conferences. There will also be a strong platform for dissemination of new monitoring methods via collaboration with the Australian Institute of Health and Welfare which will assist with promotion of these methods at state and national levels. PMID- 27558903 TI - Costs associated with functional gastrointestinal disorders and related signs and symptoms in infants: a systematic review protocol. AB - INTRODUCTION: Functional gastrointestinal disorders (FGIDs) and FGID-related signs and symptoms have a fundamental impact on the psychosocial, physical and mental well-being of infants and their parents alike. Recent reviews and studies have indicated that FGIDs and related signs and symptoms may also have a substantial impact on the budgets of third-party payers and/or parents. The objective of this systematic review is to investigate these costs. METHODS AND ANALYSIS: The population of interest is healthy term infants (under 12 months of age) with colic, regurgitation and/or functional constipation. Outcomes of interest will include the frequency and volume of reported treatments, the cost to third-party payers and/or parents for prescribed or over the counter treatments, visits to health professionals and changes in infant formula purchases, and the loss of income through time taken off work and out of pocket costs. Relevant studies will be identified by searching databases from 2005 onwards (including MEDLINE, EMBASE, PsycINFO, NEXIS, DARE, Health Technology Assessment database, National Health Service Economic Evaluation Database and others), conferences from the previous 3 years and scanning reference lists of eligible studies. Study selection, data extraction and quality assessment will be conducted by two independent reviewers and disagreements resolved in discussion with a third reviewer. Quality assessment will involve study design-specific checklists. Relevant studies will be summarised narratively and presented in tables. An overview of treatments and costs will be provided, with any geographical or other differences highlighted. An assessment of how the totals for cost differ across countries and elements that contribute to the differences will be generated. ETHICS AND DISSEMINATION: This is a systematic review of published studies that will be submitted for publication to a peer-reviewed journal. Ethical committee approval is not required. TRIAL REGISTRATION NUMBER: CRD42016033119. PMID- 27558905 TI - Lipid profile, inflammation, and oxidative status in peri- and postmenopausal women. AB - OBJECTIVE: To evaluate the effect of perimenopause and postmenopause on lipid profile, inflammation, and oxidative stress in women. METHODS: This cross sectional study included 117 women (47 +/- 6 years) classified as perimenopausal (n = 47), postmenopausal (n = 40), or non-menopausal (n = 30). In serum, we analyzed lipid profile, tumor necrosis factor-alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), and C-reactive protein (CRP). Pro-oxidant status was assessed by thiobarbituric acid reactive substances (TBARS) and protein carbonyls. Antioxidant defense was performed by analysis of superoxide dismutase (SOD) and catalase activities. RESULTS: Compared to non-menopausal women, triacylglycerols (TG) were similar, total cholesterol and LDL-C were higher in perimenopausal and postmenopausal women, while HDL-C concentrations were decreased. TNF-alpha and IL 1alpha were higher in postmenopausal women, while CRP concentrations were elevated in both peri-and postmenopausal women (p < 0.05). TBARS and carbonyls were increased in peri- and postmenopausal women (p < 0.05). SOD and CAT activities were decreased in postmenopausal women (p < 0.05) and elevated in perimenopausal women. CONCLUSION: Menopausal transition and postmenopause were associated with dyslipidemia, inflammation, and unbalanced oxidative status exposing women to cardiovascular risk. PMID- 27558906 TI - Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models. AB - AIM: To demonstrate that exosomes (exo) could increase the therapeutic index of doxorubicin (DOX). MATERIALS & METHODS: Exosomes were characterized by nanoparticle tracking analysis and western blot. Tissue toxicity was evaluated by histopathological analysis and drug efficacy by measuring tumor volume. DOX biodistribution was analyzed by MS. RESULTS: Exosomal doxorubicin (exoDOX) avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells. For this reason, mice can be treated with higher concentration of exoDOX thus increasing the efficacy of DOX as demonstrated in breast and ovarian mouse tumors. CONCLUSION: ExoDOX is safer and more effective than free DOX. Importantly, the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer was utilized for providing a new therapeutic opportunity. PMID- 27558907 TI - Emergent nanoscale superparamagnetism at oxide interfaces. AB - Atomically sharp oxide heterostructures exhibit a range of novel physical phenomena that are absent in the parent compounds. A prominent example is the appearance of highly conducting and superconducting states at the interface between LaAlO3 and SrTiO3. Here we report an emergent phenomenon at the LaMnO3/SrTiO3 interface where an antiferromagnetic Mott insulator abruptly transforms into a nanoscale inhomogeneous magnetic state. Upon increasing the thickness of LaMnO3, our scanning nanoSQUID-on-tip microscopy shows spontaneous formation of isolated magnetic nanoislands, which display thermally activated moment reversals in response to an in-plane magnetic field. The observed superparamagnetic state manifests the emergence of thermodynamic electronic phase separation in which metallic ferromagnetic islands nucleate in an insulating antiferromagnetic matrix. We derive a model that captures the sharp onset and the thickness dependence of the magnetization. Our model suggests that a nearby superparamagnetic-ferromagnetic transition can be gate tuned, holding potential for applications in magnetic storage and spintronics. PMID- 27558908 TI - Photolysis of Carbonyl Diisocyanate: Generation of Isocyanatocarbonyl Nitrene and Diazomethanone. AB - The stepwise decomposition of carbonyl diisocyanate, OC(NCO)2 , has been studied by using IR spectroscopy in solid argon matrices at 16 K. Upon irradiation with an ArF laser (lambda=193 nm), carbonyl diisocyanate split off CO and furnished a new carbonyl nitrene, OCNC(O)N, in its triplet ground state. Two conformers of the nitrene, syn and anti, that were derived from the two conformers of OC(NCO)2 (62 % syn-syn and 38 % syn-anti) were identified and characterized by combining IR spectroscopy and quantum chemical calculations. Subsequent irradiation with visible light (lambda>395 nm) caused the Curtius rearrangement of the nitrene into OCNNCO. In addition to the expected decomposition products, N2 and CO, further photolysis of OCNNCO with the ArF laser yielded NOCN, through a diazomethanone (NNCO) intermediate. To further validate our proposed reaction mechanism, ArF-laser photolysis of the closely related NNNNCO and cyclo-N2 CO in solid argon matrices were also studied. The observations of NOCN and in situ CO trapped product OCNNCO provided indirect evidence to support the initial generation of NNCO as a common intermediate during the laser photolysis of OCNNCO, NNNNCO, and cyclo-N2 CO. PMID- 27558909 TI - Protective effect of salidroside against bone loss via hypoxia-inducible factor 1alpha pathway-induced angiogenesis. AB - Hypoxia-inducible factor (HIF)-1alpha plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1alpha expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1alpha-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1alpha signalling. PMID- 27558910 TI - Three-dimensional saline-contrast sonovaginocervicography or virtual speculoscopy with HDlive: potential diagnostic tool for women with intact hymen or uterovaginocervical complex malformation. PMID- 27558911 TI - Group B streptococcus antimicrobial resistance in neonates born to group B streptococcus-colonized mothers: Single-center survey. AB - AIM: In this study, we collected group B streptococcus (GBS) screening data and analyzed screening rate, antimicrobial resistance rate, and neonatal observation room (NOR) admission rate due to inadequate chemoprophylaxis. METHODS: The GBS screening data for January 2006-December 2013 were retrospectively collected and analyzed. We also collected data for neonates admitted to NOR due to inadequate chemoprophylaxis during the period 1 April 2010-31 December 2013. RESULTS: A total of 12 200 pregnant women received rectovaginal culture during the 8-year study period. The overall screening rate was 53.8% and maternal colonization rate was 20.7%. The GBS screening rate increased remarkably, from 23.2% in 2006 to 70% in 2013. Antimicrobial resistance was common. The resistance rates for each antimicrobial used in pregnancy were as follows: clindamycin, 49.51%; erythromycin, 49.51%. A total of 297 neonates were admitted to NOR due to inadequate antibiotic prophylaxis during 1 April 2010-31 December 2013. The overall NOR admission rate due to inadequate chemoprophylaxis was 2.67%, and the inadequate chemoprophylaxis rate for those GBS colonized mothers was 19.6%. None of these 297 infants had positive blood culture for GBS sepsis. CONCLUSION: The GBS screening rate increased remarkably, reaching 70% in 2013. The NOR admission rate due to inadequate chemoprophylaxis was 2.67% and there was no early onset GBS disease in a total of 11 123 deliveries in this 4-year cohort study. PMID- 27558912 TI - {[CuSn5 Sb3 ](2-) }2 : A Dimer of Inhomogeneous Superatoms. AB - Reaction of the binary Zintl anion (Sn2 Sb2 )(2-) with the beta-diketiminato complex [LCu(NCMe)] (L=nacnac=[(N(C6 H3 (i) Pr2 -2,6)C(Me))2 CH](-) ) in ethylenediamine or DMF affords the ternary cluster dimer {[CuSn5 Sb3 ](2-) }2 (1) as its [K(crypt-222)](+) salt. The chemical formulation of 1 is supported by energy-dispersive X-ray spectroscopy (EDX) and quantum chemical calculations. Each monomeric part of the dimer represents a trimetallic "[CuSn5 Sb3 ](2-) " cluster, with an architecture in between a tricapped trigonal prism and a capped square antiprism. As shown by quantum chemical investigations, the presence of Sb atoms and, in particular, of Cu atoms in the cluster skeleton makes the monomeric unit behave like an inhomogeneous superatom, which clearly prefers to dimerize, thereby producing a relatively short, yet virtually non-bonding Cu???Cu distance. PMID- 27558913 TI - Changes in plastid proteome and structure in arbuscular mycorrhizal roots display a nutrient starvation signature. AB - During arbuscular mycorrhizal symbiosis, arbuscule-containing root cortex cells display a proliferation of plastids, a feature usually ascribed to an increased plant anabolism despite the lack of studies focusing on purified root plastids. In this study, we investigated mycorrhiza-induced changes in plastidic pathways by performing a label-free comparative subcellular quantitative proteomic analysis targeted on plastid-enriched fractions isolated from Medicago truncatula roots, coupled to a cytological analysis of plastid structure. We identified 490 root plastid protein candidates, among which 79 changed in abundance upon mycorrhization, as inferred from spectral counting. According to cross-species sequence homology searches, the mycorrhiza-responsive proteome was enriched in proteins experimentally localized in thylakoids, whereas it was depleted of proteins ascribed predominantly to amyloplasts. Consistently, the analysis of plastid morphology using transmission electron microscopy indicated that starch depletion associated with the proliferation of membrane-free and tubular membrane containing plastids was a feature specific to arbusculated cells. The loss of enzymes involved in carbon/nitrogen assimilation and provision of reducing power, coupled to macromolecule degradation events in the plastid-enriched fraction of mycorrhizal roots that paralleled lack of starch accumulation in arbusculated cells, lead us to propose that arbuscule functioning elicits a nutrient starvation and an oxidative stress signature that may prime arbuscule breakdown. PMID- 27558914 TI - Construction of a compatible Gateway-based co-expression vector set for expressing multiprotein complexes in E. coli. AB - We report the construction of a versatile Gateway-based co-expression vector set for producing multiprotein complexes in Escherichia coli. The set consists of two groups of three vectors (pCoGW and pCo0GW), each having a specific antibiotic resistance gene, a compatible origin of replication and allowing cloning of up to two genes, each under control of its own T7 promoter. To validate the set, 33 (co )expression plasmids encoding fluorescent protein (GFP, DsRed and ECFP) have been generated. Protein expression levels were quantified and (co-)expression visualized by fluorescent microscopy. The results illustrate the applicability of these vectors in co-expression studies. PMID- 27558915 TI - Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity. AB - CONTEXT: The genus Xylopia L. (Annonaceae) includes aromatic plants that have both nutritional and medicinal uses. Essential oils of Xylopia species have antitumour effects. However, the efficacy of the essential oil from the fruit of Xylopia langsdorffiana St. Hil & Tul. (EOX) has not been examined. OBJECTIVE: EOX was evaluated to determine its chemical composition, antitumour activity and toxicity. MATERIALS AND METHODS: EOX was obtained from fresh fruits of X. langsdorffiana subjected to hydrodistillation, and gas chromatography-mass spectrometry was used to characterize the chemical composition of EOX. The toxicity of EOX was evaluated using haemolysis, acute toxicity and micronucleus assays. The in vitro antitumour activity of EOX was investigated using the sulforhodamine B assay. The sarcoma 180 murine tumour model was used to evaluate the in vivo antitumour activity and toxicity of EOX (50 and 100 mg/kg) after 7 d of treatment. RESULTS: The major components of EOX were alpha-pinene (34.57%) and limonene (31.75%). The HC50 (concentration producing 50% haemolysis) was 293.6 MUg/ml. EOX showed greater selectivity for the leukaemia cell line K562, with total growth inhibition (TGI) (concentration producing TGI) of 1.8 MUg/ml, and for multidrug-resistant ovarian tumour cell line NCI/ADR-RES (TGI of 45.4 MUg/ml). The LD50 was approximately 351.09 mg/kg. At doses of 50 and 100 mg/kg, EOX inhibited the in vivo growth of sarcoma 180 by 38.67 and 54.32%, respectively. EOX displayed minor hepatic alterations characteristic of acute hepatitis and induced no genotoxicity. CONCLUSION: EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies. PMID- 27558917 TI - Why Is the One-Group Pretest-Posttest Design Still Used? AB - The one-group pretest-posttest pre-experimental design has been widely criticized, yet continues to be used in some clinical nursing research studies. This editorial explains what is wrong with the design, suggests reasons for its continued use, and gives some recommendations regarding what can be done about it. PMID- 27558918 TI - A robust ambient temperature collection and stabilization strategy: Enabling worldwide functional studies of the human microbiome. AB - As reports on possible associations between microbes and the host increase in number, more meaningful interpretations of this information require an ability to compare data sets across studies. This is dependent upon standardization of workflows to ensure comparability both within and between studies. Here we propose the standard use of an alternate collection and stabilization method that would facilitate such comparisons. The DNA Genotek OMNIgene?Gut Stool Microbiome Kit was compared to the currently accepted community standard of freezing to store human stool samples prior to whole genome sequencing (WGS) for microbiome studies. This stabilization and collection device allows for ambient temperature storage, automation, and ease of shipping/transfer of samples. The device permitted the same data reproducibility as with frozen samples, and yielded higher recovery of nucleic acids. Collection and stabilization of stool microbiome samples with the DNA Genotek collection device, combined with our extraction and WGS, provides a robust, reproducible workflow that enables standardized global collection, storage, and analysis of stool for microbiome studies. PMID- 27558920 TI - Poor reporting and documentation in drug-associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis - Lessons for medication safety. PMID- 27558921 TI - A Highly Selective Potassium Sensor for the Detection of Potassium in Living Tissues. AB - The development of highly selective sensors for potassium is of great interest in biology. Two new hydrosoluble potassium sensors (Calix-COU-Alkyne and Calix-COU Am) based on a calix[4]arene bis(crown-6) and an extended coumarin were synthesized and characterized. The photophysical properties and complexation studies of these compounds have been investigated and show high molar extinction coefficients and high fluorescence quantum yields. Upon complexation with potassium in the millimolar concentration range, an increase of one- and two photon fluorescence emission is detected. A twofold fluorescence enhancement is observed upon excitation at lambda=405 nm. The ligands present excellent selectivity for potassium in the presence of various competitive cations in water and in a physiological medium. The photophysical properties are not affected by the presence of a large amount of competing cations (Na+ , Ca2+ , Mg2+ , etc.). Ex vivo measurements on mouse hippocampal slices show that Calix-COU-Alkyne accumulates extracellularly and does not alter the neuronal activity. Furthermore, the sensor can be utilized to monitor slow extracellular K+ increase induced by inhibition of K+ entry into the cells. PMID- 27558922 TI - Direct Fluorescent Detection of Blood Potassium by Ion-Selective Formation of Intermolecular G-Quadruplex and Ligand Binding. AB - G-quadruplex analogues have been widely used as molecular tools for detection of potassium ion (K(+)). However, interference from a higher concentration of sodium ion (Na(+)), enzymatic degradation of the oligonucleotide, and background absorption and fluorescence of blood samples have all limited the use of G quadruplex for direct detection of K(+) in blood samples. Here, we reported, for the first time, an intermolecular G-quadruplex-based assay capable of direct fluorescent detection of blood K(+). Increased stringency of intermolecular G quadruplex formation based on our screened G-rich oligonucleotide (5'-TGAGGGA GGGG-3') provided the necessary selectivity for K(+) against Na(+) at physiological ion level. To increase long-term stability of oligonucleotide in blood, the screened oligonucleotide was modified with an inverted thymine nucleotide whose 3'-terminus was connected to the 3'-terminus of the upstream nucleotide, acting as a blocking group to greatly improve antinuclease stability. Lastly, to avoid interference from background absorption and autofluorescence of blood, a G-quadruplex-binding, two-photon-excited ligand, EBMVC-B, was synthesized and chosen as the fluorescence reporter. Thus, based on selective K(+) ion-induced formation of intermolecular G-quadruplex and EBMVC-B binding, this approach could linearly respond to K(+) from 0.5 to 10 mM, which matches quite well with the physiologically relevant concentration of blood K(+). Moreover, the system was highly selective for K(+) against other metal ions, including Na(+), Ca(2+), Mg(2+), Zn(2+) common in blood. The practical application was demonstrated by direct detection of K(+) from real blood samples by two-photon fluorescence technology. To the best of our knowledge, this is the first attempt to exploit molecular G-quadruplex-based fluorescent sensing for direct assay of blood target. As such, we expect that it will promote the design and practical application of similar DNA-based sensors in complex real systems. PMID- 27558923 TI - Low-income mothers' feeding goals predict observed home mealtime and child feeding practices. AB - BACKGROUND: Mothers' goals are important for health behavior change, and engagement in child obesity interventions. It is unknown if maternal feeding goals are associated with observed home mealtime or feeding practices. The objective of this study was to examine the association of four common feeding goals (restrict junk food, promote fruit or vegetable intake, promote autonomy in eating and prevent obesity) with mothers' observed home mealtime and feeding practices. METHODS: Low-income mothers (N = 265) of children (mean child age 70.8 months) participated in a semi-structured interview about child feeding. A coding scheme was developed and reliably applied to identify mothers' feeding goals from transcripts. Mothers' observed home mealtime and feeding practices were reliably coded from home mealtimes and a laboratory eating protocol. Mothers completed a questionnaire and reported demographics. Participant weights and heights were obtained. Regression models were used to test the association of each feeding goal with observed maternal practices, controlling for covariates. RESULTS: The goal of restricting junk food was associated with the child always eating at a table (OR 2.87, 95% CI (1.39-5.96) p = 0.005), but not with the mother restricting junk food. The goal of promoting fruit or vegetable intake was associated with observationally promoting vegetables (OR 1.41, 95% CI (1.09 1.84), p = 0.01). The goals of promoting autonomy and preventing obesity were not associated with any observed maternal home mealtime or feeding practices. CONCLUSIONS: While mothers' goals to restrict junk food and promote fruit or vegetable intake were associated with observed home mealtime and feeding practices, promoting autonomy and preventing obesity were not. Increased understanding of why low-income mothers may not translate certain feeding goals into practices may inform childhood obesity interventions. PMID- 27558925 TI - Microbiota: relevant player in thiopurine metabolisation? PMID- 27558924 TI - A coding variant in FTO confers susceptibility to thiopurine-induced leukopenia in East Asian patients with IBD. AB - OBJECTIVE: Myelosuppression is a life-threatening complication of thiopurine therapy, and the incidence of thiopurine-induced myelosuppression is higher in East Asians than in Europeans. We investigated genetic factors associated with thiopurine-induced leukopenia in patients with IBD. DESIGN: A genome-wide association study (GWAS) was conducted in thiopurine-treated patients with IBD, followed by high-throughput sequencing of genes identified as significant in the GWAS or those involved in thiopurine metabolism (n=331). Significant loci associated with thiopurine-induced leukopenia were validated in two additional replication cohorts (n=437 and n=330). Functional consequences of FTO (fat mass and obesity-associated) variant were examined both in vitro and in vivo. RESULTS: The GWAS identified two loci associated with thiopurine-induced leukopenia (rs16957920, FTO intron; rs2834826, RUNX1 intergenic). High-throughput targeted sequencing indicated that an FTO coding variant (rs79206939, p.A134T) linked to rs16957920 is associated with thiopurine-induced leukopenia. This result was further validated in two replication cohorts (combined p=1.3*10-8, OR=4.3). The frequency of FTO p.A134T is 5.1% in Koreans but less than 0.1% in Western populations. The p.A134T variation reduced FTO activity by 65% in the nucleotide demethylase assay. In vivo experiments revealed that Fto-/- and Fto+/- mice were more susceptible to thiopurine-induced myelosuppression than wild-type mice. CONCLUSIONS: The results suggest that the hypomorphic FTO p.A134T variant is associated with thiopurine-induced leukopenia. These results shed light on the novel physiological role of FTO and provide a potential pharmacogenetic biomarker for thiopurine therapy. PMID- 27558926 TI - Use of an Absorbable Urethral Stent for the Management of a Urethral Stricture in a Stallion. AB - OBJECTIVE: To describe the successful management of a urethral stricture with an absorbable stent in a stallion. STUDY DESIGN: Clinical report. ANIMALS: Stallion with a urethral stricture. RESULTS: A 12-year-old Thoroughbred breeding stallion was evaluated for acute onset of colic. Uroperitoneum because of presumptive urinary bladder rupture, with urethral obstruction by a urethrolith, was diagnosed. The uroperitoneum was treated conservatively. The urethrolith was removed through a perineal urethrotomy. Approximately 15 weeks after urethrolith removal, the stallion presented with a urethral stricture. The stricture was unsuccessfully treated with an indwelling urinary catheter and 4 attempts at balloon dilation. Eight weeks after diagnosis of stricture, an absorbable polydioxanone (20 mm * 80 mm) urethral stent was implanted under percutaneous, ultrasound guidance. Urethroscopy was performed at 70, 155, and 230 days after stent placement and the endoscope passed through the affected site without complication. Urethroscopy at 155 days showed the stent had been reabsorbed. Follow-up 20 months after stent placement reports the stallion was able to void a normal urine stream. CONCLUSIONS: Absorbable urethral stent placement was a feasible treatment for urethral stricture in this stallion. PMID- 27558927 TI - Chapter 4 - Treatment of Wounds. PMID- 27558928 TI - Clinical impact of magnetic resonance neurography in patients with brachial plexus neuropathies. AB - OBJECTIVE: To study the impact of brachial plexus MR neurography (MRN) in the diagnostic thinking and therapeutic management of patients with suspected plexopathy. METHODS: MRN examinations of adult brachial plexuses over a period of 18 months were reviewed. Relevant data collection included-patient demographics, clinical history, pre-imaging diagnostic impression, pre-imaging treatment plan, post-imaging diagnosis, post-imaging treatment plan, surgical notes and electrodiagnostic (ED) results. Impact of imaging on the pre-imaging clinical diagnosis and therapeutic management were classified as no change, mild change or substantial change. RESULTS: Final sample included 121 studies. The common aetiologies included inflammatory in 31 (25.6%) of 121 patients, trauma in 29 (23.9%) of 121 patients and neoplastic in 26 (21.5%) of 121 patients. ED tests were performed in 47 (38.8%) of 121 patients and these showed concordance with MRN findings in 31 (66.0%) of 47 patients. Following MRN, there was change in the pre-imaging clinical impression for 91 (75.2%) of 121 subjects, with a mild change in diagnosis in 57 (47.1%) of 121 patients and a substantial change in 34 (28.0%) of 121 patients. 19 (15.7%) of 121 patients proceeded to therapies that would not have been performed in the same manner without the information obtained from MRN. CONCLUSION: MRN of the brachial plexus significantly impacts clinical decision-making and should be routinely performed in suspected brachial plexopathy. Advances in knowledge: MRN significantly impacts the diagnostic thinking and therapeutic management of patients with suspected brachial plexopathy. MRN not only provides concordant information to ED tests in majority of cases, but also supplements with additional diagnostic data in patients who are ED negative. PMID- 27558929 TI - Plasma thrombin-cleaved osteopontin as a potential biomarker of acute atherothrombotic ischemic stroke. AB - We investigated whether thrombin-cleaved osteopontin N-terminal is useful as a blood biomarker of acute atherothrombotic ischemic stroke. Acute ischemic stroke patients were prospectively evaluated with brain magnetic resonance imaging and cardiac evaluations for etiological diagnosis according to the Trial of Org 10172 in Acute Stroke Treatment classification. They were divided into the atherothrombotic and non-atherothrombotic groups. Thrombin-cleaved osteopontin N terminal, osteopontin, matrix metalloproteinase-9, S100B, C-reactive protein and D-dimer levels were measured from blood samples collected at admission. After excluding patients who met the exclusion criteria or had stroke of other/undetermined etiology, 60 of the 100 patients initially enrolled were included in the final analysis. The ischemic stroke subtypes were atherothrombotic (n=28, 46.7%), cardioembolic (n=19, 31.7%) and lacunar (n=13, 21.7%). Thrombin-cleaved osteopontin N-terminal and matrix metalloproteinase-9 levels were significantly higher in the atherothrombotic than in the non atherothrombotic group (median (interquartile range): 5.83 (0.0-8.6 ) vs. 0.0 (0.0-3.3) pmol l-1, P=0.03 and 544 (322-749 ) vs. 343 (254-485) ng ml-1, P=0.01, respectively). After adjustment for the prevalence of hypertension, diabetes and dyslipidemia, thrombin-cleaved osteopontin N-terminal levels of >5.47 pmol l-1 (odds ratio, 16.81; 95% confidence interval, 3.53-80.10) and matrix metalloproteinase-9 levels of >605.5 ng ml-1 (6.59; 1.77-24.60) were identified as independent predictors of atherothrombosis. Within 3 h from stroke onset, only thrombin-cleaved osteopontin N-terminal independently predicted atherothrombosis and thus may add valuable, time-sensitive diagnostic information in the early evaluation of ischemic stroke, especially the atherothrombotic subtype. PMID- 27558930 TI - Monitoring and evaluation of out-of-office blood pressure during pregnancy. AB - Blood pressure (BP) is important to measure during pregnancy because it provides the basis for classifying hypertension, which has several etiologies. Similarly, monitoring home and ambulatory BP can provide useful information outside a medical setting for adults who are not pregnant. Office BP is higher during early pregnancy in primiparous women than in multiparous women, whereas out-of-office BP does not differ between them. White-coat hypertension might be benign compared with hypertension determined from ambulatory BP values that might be associated with a high risk for preeclampsia. Although reference values have been proposed on the basis of the distribution of BP among normotensive pregnant women, prognosis-based reference values are also required. PMID- 27558931 TI - Gallstone disease is associated with arterial stiffness progression. AB - Gallstones have been linked to dyslipidemia, metabolic syndrome and cardiovascular disease. Arterial stiffness is an indicator of subclinical atherosclerosis. The aim of this study was to prospectively examine the relationship between gallstone disease and arterial stiffness progression in 347 men and 454 women. These subjects were followed for 7 years. Arterial stiffness progression was measured based on increases in brachial-ankle pulse wave velocity. Changes in brachial-ankle pulse wave velocity during the study period were significantly greater in patients with gallstones than in subjects without gallstones. After adjusting for multiple risk factors, gallstone disease was found to be a significant and independent predictor of brachial-ankle pulse wave velocity progression (beta=0.189; P<0.001). In conclusion, gallstone disease is an independent predictor of arterial stiffness progression, even after adjusting for other cardiovascular risk factors. PMID- 27558932 TI - Functional regeneration of the transected recurrent laryngeal nerve using a collagen scaffold loaded with laminin and laminin-binding BDNF and GDNF. AB - Recurrent laryngeal nerve (RLN) injury remains a challenge due to the lack of effective treatments. In this study, we established a new drug delivery system consisting of a tube of Heal-All Oral Cavity Repair Membrane loaded with laminin and neurotrophic factors and tested its ability to promote functional recovery following RLN injury. We created recombinant fusion proteins consisting of brain derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) fused to laminin-binding domains (LBDs) in order to prevent neurotrophin diffusion. LBD-BDNF, LBD-GDNF, and laminin were injected into a collagen tube that was fitted to the ends of the transected RLN in rats. Functional recovery was assessed 4, 8, and 12 weeks after injury. Although vocal fold movement was not restored until 12 weeks after injury, animals treated with the collagen tube loaded with laminin, LBD-BDNF and LBD-GDNF showed improved recovery in vocalisation, arytenoid cartilage angles, compound muscle action potentials and regenerated fibre area compared to animals treated by autologous nerve grafting (p < 0.05). These results demonstrate the drug delivery system induced nerve regeneration following RLN transection that was superior to that induced by autologus nerve grafting. It may have potential applications in nerve regeneration of RLN transection injury. PMID- 27558935 TI - Corrigendum: Redox potential driven aeration during very-high-gravity ethanol fermentation by using flocculating yeast. PMID- 27558936 TI - Home Visits: Advancing Pediatric Training by Preserving Past Traditions. PMID- 27558933 TI - The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6. AB - The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure-function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis. PMID- 27558934 TI - Knockout of inositol-requiring enzyme 1alpha in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure. AB - Although numerous functions of inositol-requiring enzyme 1alpha (IRE1alpha) have been identified, a role of IRE1alpha in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus is largely unknown. Here, we showed that mice lacking IRE1alpha specifically in POMC neurons (PIKO) are lean and resistant to high-fat diet-induced obesity and obesity-related insulin resistance, liver steatosis and leptin resistance. Furthermore, PIKO mice had higher energy expenditure, probably due to increased thermogenesis in brown adipose tissue. Additionally, alpha-melanocyte-stimulating hormone production was increased in the hypothalamus of PIKO mice. These results demonstrate that IRE1alpha in POMC neurons plays a critical role in the regulation of obesity and obesity-related metabolic disorders. Our results also suggest that IRE1alpha is not only an endoplasmic reticulum stress sensor, but also a new potential therapeutic target for obesity and obesity-related metabolic diseases. PMID- 27558937 TI - Rotavirus Vaccine and Intussusception Hospitalizations. PMID- 27558938 TI - Intussusception Rates Before and After the Introduction of Rotavirus Vaccine. AB - BACKGROUND: Recent US studies have identified a small increased risk of intussusception after rotavirus vaccination, mainly after the first dose. We examined trends in intussusception hospitalizations before (2000-2005) and after (2007-2013) rotavirus vaccine introduction to assess whether this observed temporal risk translates into more hospitalized cases at the population level. METHODS: Intussusception hospitalizations in children <12 months of age were abstracted from the State Inpatient Database maintained by the Healthcare Cost and Utilization Project for 26 states that provided data from 2000 to 2013. Rates were calculated using bridged-race postcensal population estimates. Trends were analyzed by age groups (6-14 weeks, 15-24 weeks, and 25-34 weeks) based on the recommended ages for vaccine administration as well as 8-11 weeks when the majority of first doses are given. Rate ratios were calculated by using Poisson regression. RESULTS: No consistent change in intussusception hospitalization rates was observed among all children <12 months of age and among children 15 to 24 weeks and 25 to 34 weeks of age. The intussusception hospitalization rate for children aged 8 to 11 weeks was significantly elevated by 46% to 101% (range: 16.7-22.9 per 100 000) in all postvaccine years except 2011 and 2013 compared with the prevaccine baseline (11.7 per 100 000). CONCLUSIONS: The increase in the intussusception hospitalization rate in children 8 to 11 weeks when the majority of first doses of vaccine are given is consistent with recent US postlicensure studies. Given the magnitude of declines in rotavirus disease compared with this small increase in intussusception, the benefits of rotavirus vaccination outweigh the increase risk of intussusception. PMID- 27558940 TI - Comparative analysis of iron status and other hematological parameters in preeclampsia. AB - OBJECTIVE: To compare serum ferritin (SF) concentrations and other hematological parameters between patients with preeclampsia (PE) and normal pregnant women of the same gestational period who received supplemental iron during pregnancy. METHODS: Prospective, comparative, observational pilot study that included 31 women with PE and 30 healthy pregnant women, at 20 weeks' of gestation. Ferritin, iron and complete blood cell count were compared between groups. RESULTS: In comparison with controls, preeclamptic patients had a higher weight, body mass index, and arterial pressure. Serum ferritin and serum iron were higher in patients with PE (median: 36.5 MUg/l vs. 20.9 MUg/l and 103.9 MUg/dl vs. 90.8 MUg/dl) with a significant difference (P = 0.019 and P = 0.345). SF values >40 MUg/l correlated with PE (r = 0.281; P = 0.032). A platelet count less than 100 * 109/l was higher in the PE group than in the control group (13% vs. 3%, P = 0.354). CONCLUSION: Higher SF levels, despite being within normal range, were associated with PE. The incidence of thrombocytopenia was higher in preeclamptic women, however, the remaining hematological parameters were similar in both groups. PMID- 27558939 TI - Veteran Use of Health Care Systems in Rural States: Comparing VA and Non-VA Health Care Use Among Privately Insured Veterans Under Age 65. AB - OBJECTIVE: To quantify use of VA and non-VA care among working-age veterans with private insurance by linking VA data to private health insurance plan (PHIP) data. METHODS: Demographics and utilization were compared between dual users of VA and non-VA systems versus single-system users for veterans < 65 living in 2 rural Midwestern states concurrently enrolled in VA health care and a PHIP for >= 1 complete federal fiscal year from 2000 to 2010. Chi-square and t-tests were used for univariate analyses. VA reliance was computed as the percentage of visits, admissions and prescriptions in VA. Multinomial logistic regression was used to compare characteristics by dual use versus non-VA only or VA only use. RESULTS: Of 16,330 eligible veterans, 54% used both VA and non-VA services, 39% used non-VA only, and 5% used VA only. Compared with single-system use, dual use was associated with older age, priority levels 1-4, service-connected conditions, rural residence, greater years of study eligibility, and enrollment in the PHIP before VA. VA reliance was 33% for outpatient care, 14% for inpatient, and 40% for pharmacy. PHIP data substantially underestimated VA use compared to VA data; 26% who used VA health care had no VA claims in the PHIP dataset. CONCLUSIONS: Over half of working-age veterans enrolled in VA and private insurance used services in both systems. Care coordination efforts across systems should include veterans of all ages, particularly rural veterans more likely to be dual users, and better methods are needed to identify veterans with private insurance and their private providers. PMID- 27558941 TI - Functional characterization of hepatitis B virus core promoter mutants revealed transcriptional interference among co-terminal viral mRNAs. AB - Hepatitis B virus (HBV) has a 3.2 kb circular DNA genome. It employs four promoters in conjunction with a single polyadenylation signal to generate 3.5, 2.4, 2.1 and 0.7 kb co-terminal RNAs. The 3.5 kb RNA is subdivided into the precore RNA for e-antigen expression and pregenomic RNA for genome replication. When introduced to a genotype A clone, several core promoter mutations markedly enhanced HBV genome replication, but suppressed e-antigen expression through up regulation of pregenomic RNA at the expense of precore RNA. In this study, we found such mutations also diminished envelope proteins and hepatitis B surface antigen, products of the 2.1 and 2.4 kb subgenomic RNAs. Indeed, Northern blot analysis revealed overall increase in 3.5 kb RNA, but reduction in all subgenomic RNAs. To validate transcriptional interference, we subcloned 1.1*, 0.7* and 0.6* HBV genome, respectively, to a vector with or without a cytomegalovirus (CMV) promoter at the 5' end, so as to produce the pregenomic RNA, 2.4 kb RNA, and 2.1 kb RNA in large excess or not at all. Parallel transfection of the three pairs of constructs into a human hepatoma cell line confirmed the ability of pregenomic RNA to suppress all subgenomic transcripts and established the ability of the 2.4 and 2.1 kb RNAs to suppress the 0.7 kb RNA. Consistent with our findings, pregenomic RNA of the related duck HBV has been reported to interfere with transcription of the subgenomic RNAs. Transcriptional interference might explain why HBV produces so little 0.7 kb RNA and HBx protein despite a strong X promoter. PMID- 27558943 TI - Estimating the cost-effectiveness of brief interventions for heavy drinking in primary health care across Europe. AB - Background: Screening and Brief Interventions for alcohol are an effective public health measure to tackle alcohol-related harm, however relatively few countries across the European Union (EU) have implemented them widely. This may be due to a lack of understanding of the specific financial implications of such policies within each country. Methods: A novel 'meta-modelling' approach was developed based on previous SBI cost-effectiveness models for four EU countries. Data were collected on the key factors which drive cost-effectiveness for all 28 EU countries (mean per capita alcohol consumption, proportion of the population to be screened over a 10-year SBI programme; per capita alcohol-attributable mortality; per capita alcohol-attributable morbidity; mean cost of an alcohol related hospitalisation and mean SBI-delivery staff cost). Regression analysis was used to fit two meta-models estimating net programme costs and Quality Adjusted Life Years (QALYs) gained, to calculate cost-effectiveness estimates specific to each EU country. Results: Costs are dependent upon the proportion of the population covered by the screening programme, the country-specific per capita mortality and morbidity rate and the country-specific costs of GP care and hospitalisation. QALYs depend on the proportion of the population screened and per capita alcohol consumption. Despite large inter-country variability in factor values, SBI programmes are likely to be cost-effective in 24 out of 28 EU countries and cost-saving in 50% of countries. Conclusion: Implementing national programmes of SBI in primary health care would be a cost-effective means of reducing alcohol-attributable morbidity and deaths in almost all countries of the EU. PMID- 27558945 TI - Radiographic anatomy of juvenile bovine limbs. AB - Juvenile bovine patients who present with clinical signs of lameness are commonly evaluated using radiographic techniques both within a hospital setting and in a farm environment. The radiographic development of the juvenile bovine skeleton is currently poorly documented. In this study, the limbs of four heifer calves were sequentially radiographed to assess development of the juvenile bovine appendicular skeleton in the first 12 months of life. Images were acquired at three weeks, three months, six months, nine months and one year of age. The normal radiographic anatomy of the fore limbs and hindlimbs and the changes over the first 12 months are described. The majority of physes remain open throughout this period, with the exception of the proximal physes of the proximal and middle phalanges, the proximal radial physis, and the proximal humeral physis which close radiographically between 9 months and 12 months of age, and fusion of the fourth and central tarsal bones occurs between 9 months and 12 months of age. The results of this study may aid in differentiating normal and abnormal anatomy in the juvenile bovine limb. PMID- 27558944 TI - Idiopathic Choroidal Neovascularization: Intraocular Inflammatory Cytokines and the Effect of Intravitreal Ranibizumab Treatment. AB - Idiopathic choroidal neovascularization (ICNV) is a disorder that primarily affecting patients younger than 50 years and can cause severe loss of vision. Choroidal abnormalities, especially choroidal inflammation, have been thought to be involved in the pathophysiology of ICNV. However, the exact pathogenesis of ICNV remains unclear. The aim of our study was investigate the levels of 27 inflammatory cytokines in the aqueous humor of eyes with ICNV, and to determine the effect of intravitreal injection of ranibizumab (IVR) on cytokine levels. Significantly higher levels of IL-2, IL-10, IL-15, IL-17, basic FGF, and GM-CSF were observed in patients with ICNV compared with controls. However, only IL-17 levels were significantly higher in patients with ICNV compared with controls after adjusting for axial length. Furthermore, there were significant correlations between the levels of IL-10, IL-17, GM-CSF, and VEGF and the lesion area. Significant changes in visual acuity and central retinal thickness were observed after IVR. Besides VEGF, IVR also significantly reduced the levels of IL 2, IL-10, basic FGF, and IL-12, however, the IL-6 levels were significantly increased. Our results suggest that there may be an involvement of IL-17-related inflammatory processes in the etiology of ICNV. PMID- 27558946 TI - Incidence and risk factors of superficial and deep vein thrombosis associated with peripherally inserted central catheters in children. AB - : Essentials Pediatric studies on peripherally inserted central catheter (PICC) related thrombosis are scarce. This study analyzes incidence and risk factors for PICC-related venous thrombosis in children. PICC-related thrombosis is a common, and nearly always, asymptomatic complication. Echo-guided insertion and a catheter to vein ratio < 0.33 may notably decrease this complication. SUMMARY: Background Upper-extremity venous thrombosis is associated with the use of peripherally inserted central catheters (PICCs). Few pediatric studies have focused on this issue. Objectives To determine the incidence and risk factors for PICC-related superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) in children. Patients/methods An observational follow-up cohort study was conducted at a single hospital between June 2012 and June 2015. All patients receiving a PICC were enrolled and followed up, with weekly Doppler ultrasound examination of the catheterized limb until PICC removal. Patient, procedural and follow-up data were analyzed. Results In the study period, 265 PICCs were inserted (median age of patients 6.5 years, interquartile range [IQR] 2.4-13 years; median weight 20 kg, IQR 11-38 kg; 54% males; 67.9% chronically ill), and patients were followed up for a total of 9743 days. The median indwelling time was 21 days (IQR 12-37 days). During follow-up, 88 (33.2% of insertions) PICC-related thromboses (incidence rate [IR] 9.03 per 1000 catheter-days) were diagnosed, 66 (24.9%) as isolated SVT, seven (2.6%) as isolated DVT, and 15 (5.7%) as SVT with associated DVT (IR 6.78, 0.71 and 1.54 per 1000 catheter-days, respectively). Only 9.9% of patients with SVT and 18.2% of those with DVT were symptomatic. The main risk factors for PICC-related SVT and DVT were a catheter/vein ratio of > 0.33 and thrombosis of the catheterized superficial vein, respectively. Conclusions PICC related thrombosis is a common and nearly always asymptomatic complication in children, the SVT rate being approximately three times higher than the DVT rate. Optimal vein and catheter selection, yielding the lowest possible catheter/vein ratio, may decrease the rate of PICC-related thrombosis. PMID- 27558947 TI - Protective effect of lavender oil on scopolamine induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lavender essential oil (LO), an aromatic liquid extracted from Lavandula angustifolia Mill., has been traditionally used in the treatments of many nervous system diseases, and recently LO also reported to be effective for the Alzheimer's disease (AD). AIM OF THE STUDY: The improvement effect of lavender oil (LO) on the scopolamine-induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells have been evaluated. The relevant mechanism was also researched from the perspective of antioxidant effect and cholinergic system modulation. MATERIALS AND METHODS: Cognitive deficits were induced in C57BL/6J mice treated with scopolamine (1mg/kg, i.p.) and were assessed by Morris water maze (MWM) and step-through passive avoidance tests. Then their hippocampus were removed for biochemical assays (acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA)). In vitro, the cytotoxicity were induced by 4h exposure to H2O2 in PC12 and evaluated by cell viability (MTT), lactate dehydrogenase (LDH) level, nitric oxide (NO) release, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP). RESULTS: The results demonstrated that LO (100mg/kg) could improve the cognitive performance of scopolamine induced mice in behavioral tests. Meanwhile, it significantly decreased the AChE activity, MDA level, and increase SOD and GPX activities of the model. Moreover, LO (12MUg/mL) protected PC12 cells from H2O2 induced cytotoxicity by reducing LDH, NO release, intracellular ROS accumulation and MMP loss. CONCLUSIONS: It was suggested that LO could show neuroprotective effect in AD model in vivo (scopolamine-treated mice) and in vitro (H2O2 induced PC12 cells) via modulating oxidative stress and AChE activity. PMID- 27558948 TI - Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects. AIM OF THE STUDY: In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200MUg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining. RESULTS: In the diabetic group, the expressions of TLR4 and NF-kappaB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-kappaB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-alpha, IL 1beta), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including alpha-SMA, TGF beta1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups. CONCLUSIONS: Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-kappaB/IL-1beta immune pathway, suppression of NF-kappaB/TNF alpha/VCAM-1 inflammatory pathway and down-regulation of TGF-beta1/alpha SMA/Vimentin fibrosis pathway. PMID- 27558949 TI - Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1. AB - Over-expression and aberrant activation of tyrosine kinases occur frequently in human cancers. Various tyrosine kinase inhibitors (TKIs) are under clinical use, but acquisition of resistance to these drugs is a major problem. Here, we studied the interaction between two drug-resistant mutants of fibroblast growth factor receptor 1 (FGFR1), N546K and V561M, and four ATP-competitive inhibitors, ponatinib, dovitinib, PD173074 and BGJ-398. Among these protein-drug systems, the only marked reduction in affinity was that of PD173074 for the V561M mutant. We also examined the interaction of these FGFR1 variants to AMP-PNP, a nonhydrolyzable analogue of ATP, and showed that N546K showed increased affinity for the ATP analogue as compared with the wild type. These findings will help to clarify the mechanism of drug resistance in mutant tyrosine kinases. PMID- 27558950 TI - Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus. AB - Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki' and Ki determined as 30.62 +/- 7.73 nM and 153.75 +/- 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ? 300 MUM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID- 27558951 TI - Patient Insights Into the Design of Technology to Support a Strengths-Based Approach to Health Care. AB - BACKGROUND: An increasing number of research studies in the psychological and biobehavioral sciences support incorporating patients' personal strengths into illness management as a way to empower and activate the patients, thus improving their health and well-being. However, lack of attention to patients' personal strengths is still reported in patient-provider communication. Information technology (IT) has great potential to support strengths-based patient-provider communication and collaboration, but knowledge about the users' requirements and preferences is inadequate. OBJECTIVE: This study explored the aspirations and requirements of patients with chronic conditions concerning IT tools that could help increase their awareness of their own personal strengths and resources, and support discussion of these assets in consultations with health care providers. METHODS: We included patients with different chronic conditions (chronic pain, morbid obesity, and chronic obstructive pulmonary disease) and used various participatory research methods to gain insight into the participants' needs, values, and opinions, and the contexts in which they felt strengths-based IT tools could be used. RESULTS: Participants were positive toward using technology to support them in identifying and discussing their personal strengths in clinical consultation, but also underlined the importance of fitting it to their specific requirements and the right contexts of use. Participants recommended that technology be designed for use in preconsultation settings (eg, at home) and felt that it should support them in both identifying strengths and in finding out new ways how strengths can be used to attain personal health-related goals. Participants advocated use of technology to support advance preparation for consultations and empower them to take a more active role. IT tools were suggested to be potentially useful in specific contexts, including individual or group consultations with health care providers (physician, nurse, specialist, care team) in clinical consultations but also outside health care settings (eg, as a part of a self-management program). Participants' requirements for functionality and design include, among others: providing examples of strengths reported by other patients with chronic conditions, along with an option to extend the list with personal examples; giving an option to briefly summarize health-related history; using intuitive, easy-to-use but also engaging user interface design. Additionally, the findings are exemplified with a description of a low-fidelity paper prototype of a strengths-based tool, developed with participants in this study. CONCLUSIONS: Users requirements for IT support of a strengths-based approach to health care appear feasible. The presented findings reflect patients' values and lists potential contexts where they feel that technology could facilitate meaningful patient-provider communication that focuses not just on symptoms and problems, but also takes into account patients' strengths and resources. The findings can be used to inform further development of IT tools for use in clinical consultations. PMID- 27558952 TI - Influence of amino acids on gastric adaptive relaxation (accommodation) in rats as evaluated with a barostat. AB - AIM: The present study aimed to evaluate the effects of selected straight alkyl chain, hydroxylated chain and branched chain amino acids on gastric adaptive relaxation, as these have previously been shown to have differing effects on gastric emptying. MATERIALS AND METHODS: Gastric adaptive relaxation was evaluated using a barostat in rats under urethane anesthesia. The pressure within the balloon, introduced from the mouth to the stomach, was changed stepwise from 1 to 8 mmHg. The increased volume just after the increase of balloon pressure was defined as distension-induced gastric adaptive relaxation (accommodation). Amino acids were administered orally or intravenously. RESULTS: As compared with control rats administered with distilled water, those rats that were orally administered amino acids having straight alkyl chain and extra hydroxylated alkyl chain, such as glycine and l-serine, had significantly enhanced gastric adaptive relaxation, but administration of l-alanine and l-threonine did not. Branched chain amino acids, such as l-isoleucine, l-leucine and l-valine, also did not significantly influence gastric adaptive relaxation. Glycine and l-serine showed the same efficacy when administered intravenously. CONCLUSION: Among the amino acids evaluated in the present study, glycine and l-serine significantly enhanced gastric adaptive relaxation, suggesting that short alkyl chain amino acids may enhance gastric adaptive relaxation as compared with the other amino acids. These findings may suggest that glycine and l-serine would be useful in the therapy of functional dyspepsia, especially for early satiety, because the dysfunction of adaptive relaxation is one of the causes of early satiety. PMID- 27558953 TI - Hemolymphangioma of the broad ligament: A differential diagnosis for an ovarian cyst. PMID- 27558954 TI - Medically managing obesity: Offering hope or a disincentive to change? AB - OBJECTIVE: As weight loss in primary care remains minimal, Health Professionals are advised to medically manage obesity-related risk factors including blood pressure and cholesterol. This experimental study evaluated the impact of medically managing risk factors on obese patients' motivation to change their behaviour. METHODS: A vignette study with two arms: successful medical management (ie risk factors have improved) vs failed medical management (ie no change) set in three General Practices in the South of England. Overweight and obese patients (n=170) rated their behavioural intentions and beliefs after reading a vignette describing an overweight patient who had received either successful or failed medical management of their risk factors (blood pressure and cholesterol). RESULTS: Following successful medical management overweight and obese patients reported increased intentions to lose weight and a greater understanding of their condition. CONCLUSION: Medical management may change patient's understanding of their weight problem and motivate them to lose weight. PRACTICE IMPLICATIONS: Successful management relating to improvements in blood pressure and cholesterol may offer renewed hope and motivate obese patients to change their behaviour. This could be used as a teachable moment to encourage patients to see that obesity need not be an inevitable part of their lives. PMID- 27558956 TI - Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. AB - BACKGROUND: Postpartum haemorrhage is the leading cause of maternal mortality. Tranexamic acid (TXA) reduces surgical haemorrhage and the risk of death in bleeding trauma patients. OBJECTIVES: To assess the effects of TXA on risk of postpartum haemorrhage and other clinically relevant outcomes. SEARCH STRATEGY: We searched the MEDLINE, CENTRAL, EMBASE, PubMed, ClinicalTrials.gov and WHO ICTRP electronic databases to May 2015. SELECTION CRITERIA: Randomised controlled trials comparing TXA with no TXA or placebo in women giving birth vaginally or by caesarean section. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed the risk of bias for each trial. Because of data concerns we did not conduct a meta-analysis. MAIN RESULTS: We found 26 trials including a total of 4191 women. Examination of the trial reports raised concerns about the quality of the data. Eight trial reports contained identical or similar text and there were important data inconsistencies in several trials. Two trials did not have ethics committee approval. Meta-analysis of baseline variables suggested that randomisation was inadequate in many trials. CONCLUSIONS: There is no reliable evidence that TXA prevents postpartum haemorrhage during childbirth. Many of the trials conducted to date are small, low quality and contain serious flaws. TWEETABLE ABSTRACT: No evidence that TXA prevents postpartum haemorrhage. Existing trials are unreliable, with serious flaws. PMID- 27558955 TI - Molecular hydrogen suppresses activated Wnt/beta-catenin signaling. AB - Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/beta catenin signaling by promoting phosphorylation and degradation omicronf beta catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3 phosphorylation sites of beta-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the beta-catenin degradation complex, minimized the suppressive effect of H2 on beta-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of beta-catenin, as well as the beta-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H2 reduces the activation of Wnt/beta-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating beta-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/beta-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases. PMID- 27558957 TI - Changes in living arrangement, daily smoking, and risky drinking initiation among young Swiss men: a longitudinal cohort study. AB - OBJECTIVES: The aim of this study was to assess the association between changes in living arrangement and the initiation of daily smoking and monthly risky single-occasion drinking (RSOD) in a cohort of young Swiss men. STUDY DESIGN: Longitudinal cohort study. METHODS: The sample consisted of 4662 young men drawn from the Cohort Study on Substance Use Risk Factors who lived with their family at baseline. Follow-up assessments occurred 15 months later. Multiple regression models were adjusted for individual and family factors (family model), as well as for individual and peer-related factors (peer model). RESULTS: Relative to those still living with their parents at follow-up (n = 3845), those who had moved out (n = 817) were considerably more likely to have taken up smoking or RSOD after adjusting for several individual, family, and peer-related variables: OR (daily smoking) = 1.67 (95% CI 1.15-2.41) (P = 0.007) and OR (monthly RSOD) = 1.42 (95% CI 1.08-1.88) (P = 0.012). The strongest family-related predictors of smoking initiation were family structure and the lack of parental regulation and the strongest peer-related factors alcohol/drug problems in peers. Meanwhile, the strongest peer-related predictors of RSOD initiation were peer pressure (misconduct), perceived social support from friends, and perceived social support from a significant other, whereas family factors were not associated with RSOD initiation. Further subanalyses were conducted to examine the impact of different living arrangement changes on substance use initiation and revealed that living with peers at follow-up was associated with the greatest risk. CONCLUSIONS: We identified a strong association between moving out of one's parents' home and daily smoking and monthly RSOD initiation in young Swiss men. Moving out to live with peers was an especially strong predictor of substance use initiation. Campaigns that aim to prevent heavy smoking and drinking should be intensified at the end of obligatory school. PMID- 27558958 TI - Highly Efficient Electrochemical Hydrogen Evolution Reaction at Insulating Boron Nitride Nanosheet on Inert Gold Substrate. AB - It is demonstrated that electrochemical hydrogen evolution reaction (HER) proceeds very efficiently at Au electrode, an inert substrate for HER, modified with BNNS, an insulator. This combination has been reported to be an efficient electrocatalyst for oxygen reduction reaction. Higher efficiency is achieved by using the size controlled BNNS (<1 MUm) for the modification and the highest efficiency is achieved at Au electrode modified with the smallest BNNS (0.1-0.22 MUm) used in this study where overpotentials are only 30 mV and 40 mV larger than those at Pt electrode, which is known to be the best electrode for HER, at 5 mAcm(-2) and at 15 mAcm(-2), respectively. Theoretical evaluation suggests that some of edge atoms provide energetically favored sites for adsorbed hydrogen, i.e., the intermediate state of HER. This study opens a new route to develop HER electrocatalysts. PMID- 27558959 TI - Antibody-coated nanoparticles are promising molecular probes for microscopic analysis of cell behavior. PMID- 27558960 TI - Determination and purification of sesamin and sesamolin in sesame seed oil unsaponified matter using reversed-phase liquid chromatography coupled with photodiode array and tandem mass spectrometry and high-speed countercurrent chromatography. AB - In Asian countries, sesame seed oil unsaponified matter is used as a natural food additive due to its associated antioxidant effects. We determined and purified the primary lignans sesamin and sesamolin in sesame seed oil unsaponified matter using reversed-phase liquid chromatography coupled with photodiode array and tandem mass spectrometry and high-speed countercurrent chromatography. Calibration curves showed good correlation coefficients (r2 > 0.999, range 0.08 and/or 0.15 to 5 MUg/mL) with a limit of detection (at 290 nm) of 0.02 MUg/mL for sesamin and 0.04 MUg/mL for sesamolin. Sesame seed oil unsaponified matter contained 2.82% sesamin and 2.54% sesamolin, respectively. Direct qualitative analysis of sesamin and sesamolin was achieved using quadrupole mass spectrometry with positive-mode electrospray ionization. Pure (>99%) sesamin and sesamolin standards were obtained using high-speed countercurrent chromatographic purification (hexane/ethyl acetate/methanol/water; 7:3:7:3). An effective method for determining and purifying sesamin and sesamolin from sesame seed oil unsaponified matter was developed by combining these separation techniques for standardized food additives. PMID- 27558961 TI - The up-regulation of long non-coding RNA CCAT2 indicates a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition. AB - Recently, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human cancer biology. LncRNA CCAT2 is a novel identified lncRNA that was previously reported to be up-regulated in different cancers, however, its role in prostate cancer remains unclear. The aim of this study was to investigate the expression and role of lncRNA CCAT2 in prostate cancer. The expression levels of lncRNA CCAT2 in PCa tissues and cell lines (DU145 and 22RV1) were evaluated by quantitative real-time PCR (qRT-PCR), and its association with prognosis of patients was analyzed by statistical analysis. Furthermore, the effect of CCAT2 on proliferation, migration, and invasion was studied in PCa cells. We found that the expression level of CCAT2 was higher in PCa tissues and cells compared to adjacent non-tumor tissues and normal prostate stromal immortalized cells WPMY-1. Kaplan-Meier survival analysis revealed that patients with high CCAT2 expression level had poorer overall survival and progression-free survival than those with low CCAT2 expression. Furthermore, multivariate analysis showed that the status of CCAT2 expression was an independent prognostic indicator for this disease. We also found that knockdown of CCAT2 could inhibit cell growth, migration, and invasion in vitro. In addition, knockdown of CCAT2 stimulated epithelial-mesenchymal transition (EMT) through abrogating N-cadherin, vimentin expression and intensifing the expression levels of E-cadherin. In conclusion, our data suggested that lncRNA CCAT2 was a novel molecule involved in PCa progression, which provided a potential prognostic biomarker and therapeutic target for new therapies in patients with prostate cancer. PMID- 27558963 TI - Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats. AB - OBJECTIVE: The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats. PMID- 27558964 TI - Synthesis of 1,3-Substituted Cyclobutanes by Allenoate-Alkene [2 + 2] Cycloaddition. AB - A method for the [2 + 2] cycloaddition of terminal alkenes with allenoates is presented. This process allows for the rapid synthesis of 1,3-substituted cyclobutanes in high yield under simple and robust reaction conditions. PMID- 27558966 TI - Repeated use of mifepristone and levonorgestrel and their effect on the ovarian function in mice. AB - AIM: To investigate the effects of repeated mifepristone and levonorgestrel use on estrous cycle and expression of ovarian follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in mice. METHODS: Ovarian FSHR and LHR mRNA expression was measured using real-time quantitative reverse transcription-polymerase chain reaction, while the protein levels were measured using immunohistochemistry. RESULTS: Repeated use of mifepristone and levonorgestrel significantly lengthened the estrous cycle and decreased FSHR and LHR mRNA and protein expression in the ovaries of mice at 4, 24, and 48 days after discontinuing drug use. Repeated use of mifepristone and levonorgestrel had significant main effects on estrous cycle length and the mRNA expression and protein level of ovarian FSHR and LHR. Repeated mifepristone and levonorgestrel use and withdrawal time had a significant interaction with mouse estrous cycle (F = 16.65, P < 0.05), ovarian LHR and FSHR mRNA expression (F = 563.072, P < 0.05), and protein level (F = 6.536, P < 0.05). CONCLUSION: Repeated use of mifepristone and levonorgestrel can lead to sustained damage to ovarian function through inhibition of ovarian FSHR and LHR expression in mice. PMID- 27558967 TI - Pharmacokinetic and pharmacodynamic drug evaluation of tofogliflozin for the treatment of type 2 diabetes. AB - INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a new class of drugs that are increasingly used for the management of type 2 diabetes mellitus (T2DM). Among these, tofogliflozin has recently received marketing approval in Japan. AREAS COVERED: In this review, the authors summarize the pharmacokinetic and pharmacodynamic profile of tofogliflozin for the treatment of T2DM, and provide a rationale for its use in such patients. EXPERT OPINION: Despite the very promising characteristics of tofogliflozin in improvement of glycemic and metabolic parameters, a number of issues await consideration. One important question relates to the manner in which tofogliflozin mediates metabolic changes. Additionally, safety issues, namely hypoglycemia, diabetic ketoacidosis, pollakiuria and polyuria, urinary and genital tract infections, and potential other adverse events, need to be better monitored by pharmacovigilance programs. Ultimately, although tofogliflozin seems a promising agent that physicians are likely to embrace with excitement in the T2DM therapeutic area, longer duration trials are expected to verify this speculation and to increase our experience. PMID- 27558968 TI - Large fluctuations at the lasing threshold of solid- and liquid-state dye lasers. AB - Intensity fluctuations in lasers are commonly studied above threshold in some special configurations (especially when emission is fed back into the cavity or when two lasers are coupled) and related with their chaotic behaviour. Similar fluctuating instabilities are usually observed in random lasers, which are open systems with plenty of quasi-modes whose non orthogonality enables them to exchange energy and provides the sort of loss mechanism whose interplay with pumping leads to replica symmetry breaking. The latter however, had never been observed in plain cavity lasers where disorder is absent or not intentionally added. Here we show a fluctuating lasing behaviour at the lasing threshold both in solid and liquid dye lasers. Above and below a narrow range around the threshold the spectral line-shape is well correlated with the pump energy. At the threshold such correlation disappears, and the system enters a regime where emitted laser fluctuates between narrow, intense and broad, weak peaks. The immense number of modes and the reduced resonator quality favour the coupling of modes and prepares the system so that replica symmetry breaking occurs without added disorder. PMID- 27558965 TI - RNF168 and USP10 regulate topoisomerase IIalpha function via opposing effects on its ubiquitylation. AB - Topoisomerase IIalpha (TOP2alpha) is essential for chromosomal condensation and segregation, as well as genomic integrity. Here we report that RNF168, an E3 ligase mutated in the human RIDDLE syndrome, interacts with TOP2alpha and mediates its ubiquitylation. RNF168 deficiency impairs decatenation activity of TOP2alpha and promotes mitotic abnormalities and defective chromosomal segregation. Our data also indicate that RNF168 deficiency, including in human breast cancer cell lines, confers resistance to the anti-cancer drug and TOP2 inhibitor etoposide. We also identify USP10 as a deubiquitylase that negatively regulates TOP2alpha ubiquitylation and restrains its chromatin association. These findings provide a mechanistic link between the RNF168/USP10 axis and TOP2alpha ubiquitylation and function, and suggest a role for RNF168 in the response to anti-cancer chemotherapeutics that target TOP2. PMID- 27558969 TI - Impact of holoprosencephaly, exomphalos, megacystis and increased nuchal translucency on first-trimester screening for chromosomal abnormalities. AB - OBJECTIVES: To examine the prevalence of alobar holoprosencephaly, exomphalos, megacystis and nuchal translucency thickness (NT) >= 3.5 mm, the incidence and types of chromosomal abnormalities associated with these conditions and their overall impact on the rate of invasive testing and performance of screening at 11 14 weeks. METHODS: This was a prospective screening study for trisomies 21, 18 and 13 by the first-trimester combined test at three maternity units in England. RESULTS: In the study population of 108 982 singleton pregnancies, 870 (0.8%) had abnormal karyotype, including 654 (75.2%) with trisomies 21, 18 or 13 and 216 (24.8%) with other chromosomal abnormalities. The prevalence of alobar holoprosencephaly, exomphalos, megacystis and NT >= 3.5 mm was 1 in 2945, 1 in 419, 1 in 1345 and 1 in 119, respectively. Chromosomal abnormalities were observed in 78.4% of cases of holoprosencephaly, 40.8% of exomphalos, 18.5% of megacystis and 48.5% of those with NT >= 3.5 mm. The most common chromosomal abnormality associated with holoprosencephaly was trisomy 13, with exomphalos and megacystis was trisomy 18 and with increased NT was trisomy 21. Fetal karyotyping of cases with major fetal defects or increased NT would potentially detect 57% of all chromosomal abnormalities at an invasive testing rate of 1.1%. CONCLUSION: Major fetal defects and increased NT at 11-13 weeks' gestation are associated with a high risk of chromosomal abnormalities and merit invasive fetal testing. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27558970 TI - The relationship between serum uric acid and metabolic syndrome in premenopausal and postmenopausal women in the Jinchang Cohort. AB - The aim of the study was to explore the association between serum uric acid (SUA) and metabolic syndrome (MetS) in premenopausal and postmenopausal women in the Jinchang Cohort. We studied 3808 female Jinchuan Nonferrous Metals Corporation workers aged 40-60 years. Cohort data from epidemiological surveys and medical exams were used. MetS was defined using the 2009 Joint Interim Society criteria. The relationship between SUA and MetS was evaluated using multiple logistic regression after adjusting for potential confounders. MetS and hyperuricemia were more prevalent in postmenopausal women than premenopausal ones (35.3% versus 15.2% and 9.2% versus 4.2%, respectively). Premenopausal and postmenopausal women with hyperuricemia had 2.81 (95% CI: 1.72-4.61) and 2.10 (95% CI: 1.44-3.08), respectively, times the odds of having MetS than their counterparts without hyperuricemia. Even within normal SUA quartiles, only premenopausal women in the highest and second-highest quartile had 3.57 (95% CI: 2.24-5.68) and 2.78 (95% CI: 1.71-4.50), respectively, times the odds of having MetS than those in the lowest quartile. Even in the normal range, the odds ratios for MetS increased gradually according to SUA levels in all women (Ptrend < 0.001). In conclusion, there was a significant correlation between SUA levels and MetS, and the association was stronger in premenopausal women than postmenopausal ones. PMID- 27558971 TI - Synthesis of Trifluoromethylthiolated Alkenes and Ketones by Decarboxylative Functionalization of Cinnamic Acids. AB - A tunable decarboxylative trifluoromethylthiolation of cinnamic acids with AgSCF3 was developed to afford trifluoromethylthiolated alkenes or ketones by using transition metal-mediated conditions. PMID- 27558972 TI - TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models. AB - Ewing sarcoma (EWS) is the second most frequent pediatric malignant bone tumor. EWS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine TNF-Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, certain EWS cell lines appear resistant to recombinant human (rh) TRAIL-induced apoptosis. We therefore hypothesized that a TRAIL presentation at the surface of the carrier cells might overcome this resistance and trigger apoptosis. For this purpose, human adipose mesenchymal stromal/stem cells (MSC) transfected in a stable manner to express full-length human TRAIL were co-cultured with several human EWS cell lines, inducing apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL or AMG655, an antibody agonist to the death receptor, DR5. In vivo, TRAIL delivered by MSCs was able to counteract tumor progression in two orthotopic models of Ewing sarcoma, associated with caspase activation, indicating that a cell-based delivery of a potent apoptosis-inducing factor could be relevant in EWS. PMID- 27558974 TI - A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain-free controls. AB - Patients suffering from chronic pain may benefit from learning adaptive coping strategies. Consensus on efficient strategies for this group of patients is, however, lacking, and previous studies have shown inconsistent results. The present study has examined coping strategies in two distinctly different groups of chronic pain patients and a group of healthy controls. Thirty neuropathic pain (NP) patients, 28 fibromyalgia (FM) patients, and 26 pain-free healthy controls completed the Coping Strategy Questionnaire (CSQ-48/27) and rated their daily pain. The results showed that FM and NP patients did not cope differently with pain. The only difference between the groups was that FM patients felt more in control of their pain than NP patients. Both patient groups used more maladaptive/passive coping strategies, but surprisingly also more adaptive/active coping strategies than healthy controls. However, FM patients with high levels of passive strategies felt less in control than FM patients with low levels of passive strategies. This was not seen in NP patients. An important implication for clinical practice is therefore that passive coping strategies should be restructured into active ones, especially for FM patients. Otherwise, the same psychological treatment model can be applied to both groups since they use similar coping styles. PMID- 27558973 TI - Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery. AB - Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13-17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID- 27558975 TI - Simultaneous screening and analysis of antiplatelet aggregation active alkaloids from Rhizoma Corydalis. AB - CONTEXT: The rising problem of atherosclerosis and ischemic heart disease emphasizes the need to look for new antithrombotic components with effective modes of action. Corydalis yanhusuo (Y.H. Chou & Chun C. Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu (Papaveraceae) (Rhizoma Corydalis) has been used in the traditional medicines for the treatment of cardiovascular disease. OBJECTIVE: The antiplatelet aggregation compounds in Rhizoma Corydalis were screened to validate its traditional medicinal use. MATERIAL AND METHODS: Total alkaloid extract (TAE) of Rhizoma Corydalis was obtained by refluxing 100 g Rhizoma Corydalis powder with 600 mL 70% ethanol, and purified by acidification (20% HCl) and alkalization (5 M NaOH) process. Potential antiplatelet aggregation compounds in TAE were screened by a method involving platelet bio-specific extraction and HPLC-DAD/LC MS analysis. Further in vitro antiplatelet aggregation activity confirmation of TAE and seven main alkaloids were achieved by turbidimetry method within 3 h after blood collection from rabbit carotid artery, and all the test drugs were at the concentration range of 25-350 MUg/mL. Finally, HPLC-DAD was employed for the quantitative determination of seven main components in TAE. RESULTS: Five alkaloids, identified as glaucine, dehydrocorydaline, canadine, tetrahydrocoptisine and corydaline, can be specifically extracted with platelets. The results indicated that all these five alkaloids can inhibit thrombin-induced platelet aggregation in a low dose (IC50 of glaucine, dehydrocorydaline, canadine, tetrahydrocoptisine and corydaline were 49.057, 34.914, 33.547, 84.261 and 54.164 MUg/mL, respectively) as compared to TAE (IC50 = 175.426 MUg/mL) and aspirin (IC50 = 300.340 MUg/mL), while the unbound compounds (palmatine and tetrahydropalmatine) had a very weak antiplatelet effect (IC50 > 200 MUg/mL). DISCUSSION AND CONCLUSION: This study is the first reported work for antiplatelet components screening in Rhizoma Corydalis. Seven compounds were detected and identified by HPLC-DAD/LC-MS, of which five platelet-targeted compounds were discovered. PMID- 27558976 TI - Diffusion-weighted MRI for hepatocellular carcinoma screening in chronic liver disease: Direct comparison with ultrasound screening. AB - INTRODUCTION: Ultrasound is a widely utilized method of screening patients with chronic liver disease for hepatocellular carcinoma (HCC). However, the sensitivity of ultrasound for small tumours is limited. We have prospectively compared ultrasound screening with diffusion-weighted (DWI) MRI for detecting HCC. METHODS: Patients with chronic liver disease referred for ultrasound screening underwent a liver ultrasound and a liver MRI comprising free breathing DWI. Each test was independently read to determine the accuracy of each modality for detecting HCC. RESULTS: One hundred and ninety-two patients were recruited and HCC was diagnosed in six patients (3%); all of whom were detected at ultrasound screening, and five detected at MRI screening. Ultrasound had false positive studies 20 times (10%) while DWI MRI had three false-positive examinations (2%) p>=0.05. The sensitivity, specificity, positive predictive value and negative predictive values for ultrasound are 100%, 90%, 23% and 100%, respectively, while for MRI are 83%, 98%, 63% and 99%. CONCLUSION: In patients with chronic liver disease undergoing surveillance for hepatocellular carcinoma, DWI MRI screening shows similar sensitivity to screening ultrasound but with a significantly lower false-positive rate. PMID- 27558978 TI - Automated Discovery and Construction of Surface Phase Diagrams Using Machine Learning. AB - Surface phase diagrams are necessary for understanding surface chemistry in electrochemical catalysis, where a range of adsorbates and coverages exist at varying applied potentials. These diagrams are typically constructed using intuition, which risks missing complex coverages and configurations at potentials of interest. More accurate cluster expansion methods are often difficult to implement quickly for new surfaces. We adopt a machine learning approach to rectify both issues. Using a Gaussian process regression model, the free energy of all possible adsorbate coverages for surfaces is predicted for a finite number of adsorption sites. Our result demonstrates a rational, simple, and systematic approach for generating accurate free-energy diagrams with reduced computational resources. The Pourbaix diagram for the IrO2(110) surface (with nine coverages from fully hydrogenated to fully oxygenated surfaces) is reconstructed using just 20 electronic structure relaxations, compared to approximately 90 using typical search methods. Similar efficiency is demonstrated for the MoS2 surface. PMID- 27558977 TI - The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory. AB - INTRODUCTION: Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. MATERIALS AND METHODS: Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. RESULTS: Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. DISCUSSION: This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well as a role for podoplanin in plasticity-related brain neuronal functions is here proposed. PMID- 27558979 TI - Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994-2009, a registry study. AB - Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994 2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low. PMID- 27558980 TI - A Molecular Necklace: Threading beta-Cyclodextrins onto Polymers Derived from Bile Acids. AB - A molecular necklace of polypseudorotaxanes was prepared by threading beta cyclodextrins (beta-CD) onto biodegradable and thermoresponsive polyurethanes derived from bile acids. These polyurethanes were synthesized via a simple step condensation of bile acid-based dicarbonate with poly(ethylene glycol)-diamine. The beta-CD rings slide onto the poly(ethylene glycol) segments and selectively recognize the bile acid units of the polyurethane chains, whereas the poly(ethylene glycol) segments remain crystalline with a lower crystallinity. This bio-compound-derived molecular necklace can be visualized by scanning tunneling microscopy. The polypseudorotaxanes show thermosensitivity in water and the phase transition temperature may be fine-tuned by varying the molar ratios of beta-CD to the bile acid units. Such an interesting necklace model of polypseudorotaxane constructed from natural compounds may lead to the further exploration of their applications, such as as an enzyme model, due to their biological nature. PMID- 27558981 TI - Contactless conductivity detection for analytical techniques- Developments from 2014 to 2016. AB - The development of capacitively coupled contactless conductivity detection for the two-year period from mid-2014 to mid-2016 is covered in this review. This includes a survey of fundamental studies and further developments of the measuring technique reported as well as a discussion of new applications. These mostly concern capillary electrophoresis carried out in conventional capillaries as well as on microchip electrophoresis devices. The main focus is on the determination of small non-UV-absorbing organic ions and inorganic ions in different types of samples of clinical, nutritional or environmental interest. Outside of electrophoresis contactless conductivity detection is finding uses in detection in column chromatography, flow-injection analysis and industrial applications. PMID- 27558982 TI - Autophagy in vascular endothelial cells. AB - The importance of autophagy in cardiovascular physiology and cardiovascular disease is increasingly recognized; however, the precise biological effects and underlying mechanisms of autophagy in the cardiovascular system are still poorly understood. In the last few years, the effects of autophagy in endothelial cells have attracted great interests. This article provides a summary of our current knowledge on the regulatory factors, signalling mechanisms, and functional outcomes of autophagy in endothelial cells. It is suggested that in most situations, induction of an autophagic response has cytoprotective effects. The beneficial effects of autophagy in endothelial cells are likely to be context dependent, since autophagy may also contribute to cell death under certain circumstances. In addition to regulating endothelial cell survival or death, autophagy is also involved in modulating other important functions, such as nitric oxide production, angiogenesis and haemostasis/thrombosis. The mounting data will help us draw a clear picture of the roles of autophagy in endothelial cell biology and dysfunction. Given the pivotal role of endothelial dysfunction in the pathogenesis of vascular disease, disruptions of autophagy in endothelial cells are likely to have significant contributions. This is supported by some preliminary ex vivo data indicating that compromised autophagic functions may be important in the development of endothelial dysfunctions associated with diabetes and ageing. PMID- 27558983 TI - Horizontal Transfer Can Drive a Greater Transposable Element Load in Large Populations. AB - Genomes are comprised of contrasting domains of euchromatin and heterochromatin, and transposable elements (TEs) play an important role in defining these genomic regions. Therefore, understanding the forces that control TE abundance can help us understand the chromatin landscape of the genome. What determines the burden of TEs in populations? Some have proposed that drift plays a determining role. In small populations, mildly deleterious TE insertion alleles are allowed to fix, leading to increased copy number. However, it is not clear how the rate of exposure to new TE families, via horizontal transfer (HT), can contribute to broader patterns of genomic TE abundance. Here, using simulation and analytical approaches, we show that when the effects of drift are weak, exposure rate to new TE families via HT can be an important determinant of genomic copy number. If population exposure rate is proportional to population size, larger populations are expected to have a higher rate of exposure to rare HT events. This leads to the counterintuitive prediction that larger populations may carry a higher TE load. We also find that increased rates of recombination can lead to greater probabilities of TE establishment. This work has implications for our understanding of the evolution of chromatin landscapes, genome defense by RNA silencing, and recombination rates. PMID- 27558984 TI - Chemoembolization with drug eluting beads preloaded with irinotecan (DEBIRI) vs doxorubicin (DEBDOX) as a second line treatment for liver metastases from cholangiocarcinoma: a preliminary study. AB - OBJECTIVE: The aim of our preliminary study was to compare the efficacy of drug eluting beads preloaded with irinotecan (DEBIRI) vs drug-eluting beads preloaded with doxorubicin (DEBDOX) as second-line treatment of unresectable liver metastases from cholangiocarcinoma (CCA). METHODS: In 2013, 10 patients affected by multiple liver metastases from CCA, resistant to the first-line chemotherapy regimen, were enrolled: 5 patients were submitted to lobar/segmental transarterial chemoembolization (TACE) with DEBIRI (100-mg irinotecan/1 vial) and 5 patients with DEBDOX (50-mg doxorubicin/1 vial), performed every 3 weeks. Patients treated with DEBIRI received antipain premedication consisting of 30-mg of morphine and 3-4 ml of intra-arterial lidocaine. Complications and efficacy were assessed (response evaluation criteria in solid tumour 1.1). RESULTS: A total of 32 TACE were performed (mean: 3.2 TACE/patient), all well tolerated, with only 1 case of asymptomatic cholecystitis spontaneously recovered. Response rates of patients treated with DEBDOX and DEBIRI were: 4/5 progressive disease and 1/5 partial response vs 2/5 partial response, 2/5 stable disease and 1/5 progressive disease, respectively, with the appearance of variable necrosis percentage. Progression-free survival from the first procedure and progressive disease were 12.67 weeks for DEBIRI and 15.78 weeks for DEBDOX, respectively. Overall survival from time of primary diagnosis was 176 weeks for DEBIRI and 125 weeks for DEBDOX, respectively. CONCLUSION: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment for hepatic metastases from CCA. Antipain drug administration and the use of the microcatheter led to a good treatment tolerability and a low complication rate. Advances in knowledge: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second line treatment of hepatic metastases from CCA; further studies involving a larger cohort of patients are needed. PMID- 27558985 TI - Changes in the clinical presentation of patients with rheumatoid arthritis from the early 1990s to the years 2010: earlier identification but more severe patient reported outcomes. PMID- 27558986 TI - Tofacitinib for polyarteritis nodosa: a tailored therapy. PMID- 27558987 TI - Remission in systemic lupus erythematosus: durable remission is rare. AB - INTRODUCTION: Remission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in SLE, DORIS) to a large clinical cohort to estimate rates and predictors of remission. METHODS: We applied the DORIS definitions of Clinical Remission, Complete Remission (requiring negative serologies), Clinical Remission on treatment (ROT) and Complete ROT. 2307 patients entered the cohort from 1987 to 2014 and were seen at least quarterly. Patients not in remission at cohort entry were followed prospectively. We used the Kaplan-Meier approach to estimate the time to remission and the time from remission to relapse. Cox regression was used to identify baseline factors associated with time to remission, adjusting for baseline disease activity and baseline treatment. RESULTS: The median time to remission was 8.7, 11.0, 1.8 and 3.1 years for Clinical Remission, Complete Remission, Clinical ROT and Complete ROT, respectively. High baseline treatment was the major predictor of a longer time to remission, followed by high baseline activity. The median duration of remission for all definitions was 3 months. African-American ethnicity, baseline low C3 and baseline haematological activity were associated with longer time to remission for all definitions. Baseline anti dsDNA and baseline low C4 were associated with longer time to Complete Remission and Complete ROT. Baseline low C4 was also negatively associated with Clinical Remission. CONCLUSIONS: Our results provide further insights into the frequency and duration of remission in SLE and call attention to the major role of baseline activity and baseline treatment in predicting remission. PMID- 27558988 TI - Synthesis, Characterization, and Electronic Structures of Porphyrins Fused with Polycyclic Aromatic Ring Systems. AB - A series of porphyrins fused with acenaphthylene, phenanthroline, and benzofluoranthene polycyclic aromatic rings were prepared by means of a 3+1 porphyrin synthesis approach and subsequent retro-Diels-Alder reaction of bicyclo[2.2.2]octadiene-fused precursors. Analysis of the magnetic circular dichroism spectra and the results of time-dependent DFT calculations are used to identify the reasons for the trends observed in the wavelengths and relative intensities of the Q bands of the products. Michl's perimeter model is used as a conceptual framework to explain the changes in the relative energies of the frontier pi-molecular orbitals. PMID- 27558990 TI - Chapter 5 - Invasive treatment. PMID- 27558989 TI - The interplay of crack hopping, delamination and interface failure in drying nanoparticle films. AB - Films formed through the drying of nanoparticle suspensions release the build-up of strain through a variety of different mechanisms including shear banding, crack formation and delamination. Here we show that important connections exist between these different phenomena: delamination depends on the dynamics of crack hopping, which in turn is influenced by the presence of shear bands. We also show that delamination does not occur uniformly across the film. As cracks hop they locally initiate the delamination of the film which warps with a timescale much longer than that associated with the hopping of cracks. The motion of a small region of the delamination front, where the shear component of interfacial crack propagation is believed to be enhanced, results in the deposition of a complex zig-zag pattern on the supporting substrate. PMID- 27558991 TI - Extraction of a migrated coil from the Enterprise stent strut using a Solitaire AB stent. AB - A 56-year-old woman was admitted to stent-assisted coiling for a 2-mm A1 aneurysm of the left anterior cerebral artery and a left 3-mm internal carotid artery aneurysm. While coiling the A1 aneurysm, the first 2 mm * 20 mm coil migrated through the 4.5 mm * 37 mm Enterprise stent struts, lodging at the distal anterior cerebral artery. A 4 mm * 15 mm Solitaire AB stent was used successfully in this case to remove the displaced coil. The A1 aneurysm was re-treated with a 2 mm * 40 mm coil after placement of the Enterprise stent, and the ophthalmic ICA aneurysm was also coiled through the stent struts. The patient was neurologically intact after treatment. PMID- 27558992 TI - Serial magnetic resonance imaging findings of intracerebral spread of listeria utilising subcortical U-fibres and the extreme capsule. AB - We present a case of Listeria monocytogenes cerebral abscess with axonal spread via the subcortical U-fibres and extreme capsule on magnetic resonance imaging, with follow-up studies demonstrating serial reduction in oedema and enhancement pattern of the white-matter fibre tracts following antimicrobial treatment. We discuss the microbiological mechanism of bacterial mobility to account for these unique imaging features. Recognition of this distinct pattern of spread of L. monocytogenes cerebral abscess may aid in diagnosis and enable early microbiological culture and treatment. PMID- 27558993 TI - Stent-assisted coil embolisation for bilateral vertebral artery dissecting aneurysms presenting with subarachnoid haemorrhage. AB - Bilateral dissecting aneurysms presenting with subarachnoid haemorrhage are rare. The treatment strategy for bilateral vertebral artery dissecting aneurysms is controversial because the contralateral vertebral artery is already dissected and can easily undergo enlargement or bleed after non-reconstructive treatment procedures such as trapping or proximal occlusion. Here, we report a case of bilateral vertebral artery dissecting aneurysm presenting with subarachnoid haemorrhage that was treated with stent-assisted coiling for the ruptured side. A 42-year-old man was admitted to our hospital with sudden headache (WFNS grade 1). Computed tomography showed a high-density region in the basal cistern and posterior fossa with more haemorrhage on the right side (Fisher group 3). Three dimensional computed tomography and three-dimensional rotational angiography demonstrated a bilateral round protrusion on the vertebral arteries with a diameter of 5 mm just distal to the posterior inferior cerebellar artery. Stent assisted coiling was performed for the ruptured right side and conservative therapy was selected for the contralateral side. The ruptured side was well embolised, and the contralateral side was stable over the 12-month follow-up period after treatment. The treatment strategy for bilateral vertebral artery dissecting aneurysms presenting with subarachnoid haemorrhage is different from that for unilateral vertebral artery dissecting aneurysms. Non-reconstructive treatment procedures such as trapping may cause contralateral enlargement or rupture; therefore, reconstructive treatment may be appropriate for the ruptured side. PMID- 27558994 TI - Pulvinar sign in a case of anti-HU paraneoplastic encephalitis. AB - This article reports the case of a 68-year-old patient with anti-HU antibodies paraneoplastic encephalitis. The clinical manifestations were atypical and the paraclinical work-up, notably the magnetic resonance imaging (MRI) showing bilateral posterior thalamic hyperintensities (pulvinar sign), misleadingly pointed towards a variant Creutzfeld-Jakob disease. After presenting the case, the differential diagnosis of the pulvinar sign is discussed along with other important diagnostic considerations. PMID- 27558995 TI - Multilayer Network Analysis of Nuclear Reactions. AB - The nuclear reaction network is usually studied via precise calculation of differential equation sets, and much research interest has been focused on the characteristics of nuclides, such as half-life and size limit. In this paper, however, we adopt the methods from both multilayer and reaction networks, and obtain a distinctive view by mapping all the nuclear reactions in JINA REACLIB database into a directed network with 4 layers: neutron, proton, (4)He and the remainder. The layer names correspond to reaction types decided by the currency particles consumed. This combined approach reveals that, in the remainder layer, the beta-stability has high correlation with node degree difference and overlapping coefficient. Moreover, when reaction rates are considered as node strength, we find that, at lower temperatures, nuclide half-life scales reciprocally with its out-strength. The connection between physical properties and topological characteristics may help to explore the boundary of the nuclide chart. PMID- 27558996 TI - Self-Assembly of "Chalcone" Type Push-Pull Dye Molecules into Organic Single Crystalline Microribbons and Rigid Microrods for Vis/NIR Range Photonic Cavity Applications. AB - A novel supramolecular fluorescent donor-acceptor type dye molecule, (2E,4E)-1-(2 hydroxyphenyl)-5-(pyren-1-yl)penta-2,4-dien-1-one (HPPD) self-assembles in a mixture of ethanol/chloroform through intermolecular pi-pi stacking (distance ca. 3.384 A) to form J-aggregated single-crystalline microribbons displaying Fabry Perot (F-P) type visible-range optical resonance. The corresponding borondifluoride dye (HPPD-BF), with a reduced HOMO-LUMO gap, self-assembles into crystalline microrods acting as an F-P type resonator in the near-infrared (NIR) range. PMID- 27558997 TI - Corrigendum: Identifying a set of influential spreaders in complex networks. PMID- 27558998 TI - Characterization of a protein-protein interaction within the SigO-RsoA two subunit sigma factor: the sigma70 region 2.3-like segment of RsoA mediates interaction with SigO. AB - sigma factors are single subunit general transcription factors that reversibly bind core RNA polymerase and mediate gene-specific transcription in bacteria. Previously, an atypical two-subunit sigma factor was identified that activates transcription from a group of related promoters in Bacillus subtilis. Both of the subunits, named SigO and RsoA, share primary sequence similarity with the canonical sigma70 family of sigma factors and interact with each other and with RNA polymerase subunits. Here we show that the sigma70 region 2.3-like segment of RsoA is unexpectedly sufficient for interaction with the amino-terminus of SigO and the beta' subunit. A mutational analysis of RsoA identified aromatic residues conserved amongst all RsoA homologues, and often amongst canonical sigma factors, that are particularly important for the SigO-RsoA interaction. In a canonical sigma factor, region 2.3 amino acids bind non-template strand DNA, trapping the promoter in a single-stranded state required for initiation of transcription. Accordingly, we speculate that RsoA region 2.3 protein-binding activity likely arose from a motif that, at least in its ancestral protein, participated in DNA binding interactions. PMID- 27558999 TI - Expression of polycomb protein BMI-1 maintains the plasticity of basal bronchial epithelial cells. AB - The airway epithelium is altered in respiratory disease and is thought to contribute to disease etiology. A caveat to disease research is that the technique of isolation of bronchial epithelial cells from patients is invasive and cells have a limited lifespan. The aim of this study was to extensively characterize the plasticity of primary human bronchial epithelial cells that have been engineered to delay cell senescence including the ability of these cells to differentiate. Cells were engineered to express BMI-1 or hTERT using viral vector systems. Cells were characterized at passage (p) early (p5), mid (p10), and late (p15) stage for: BMI-1, p16, and CK14 protein expression, viability and the ability to differentiate at air-liquid interface (ALI), using a range of techniques including immunohistochemistry (IHC), immunofluorescence (IF), transepithelial electrical resistance (TEER), scanning electron microscopy (SEM), MUC5AC and beta tubulin (BTUB) staining. BMI-1-expressing cells maintained elevated levels of the BMI-1 protein and the epithelial marker CK14 and showed a suppression of p16. BMI-1-expressing cells had a viability advantage, differentiated at ALI, and had a normal karyotype. In contrast, hTERT-expressing cells had a reduced viability, showed limited differentiation, and had an abnormal karyotype. We therefore provide extensive characterization of the plasticity of BMI-1 expressing cells in the context of the ALI model. These cells retain properties of wild-type cells and may be useful to characterize respiratory disease mechanisms in vitro over sustained periods. PMID- 27559000 TI - Mathematical Nanotoxicoproteomics: Quantitative Characterization of Effects of Multi-walled Carbon Nanotubes (MWCNT) and TiO2 Nanobelts (TiO2-NB) on Protein Expression Patterns in Human Intestinal Cells. AB - BACKGROUND: Various applications of nanosubstances in industrial and consumer goods sectors are growing rapidly because of their useful chemical and physical properties. OBJECTIVES: Assessment of hazard posed by exposure to nanosubstances is essential for the protection of human and ecological health. METHODS: We analyzed the proteomics patterns of Caco-2/HT29-MTX cells in co-culture exposed for three and twenty four hours to two kinds of nanoparticles: multi-walled carbon nanotubes (MWCNT) and TiO2 nanobelts (TiO2-NB). For each nanosubstance cells were exposed to two concentrations of the material before carrying out proteomics analyses: 10 MUg and 100 MUg. In each case over 3000 proteins were identified. A mathematically based similarity index, which measures the changes in abundances of cellular proteins that are highly affected by exposure to the nanosubstances, was used to characterize toxic effects of the nanomaterials. RESULTS: We identified 8 and 25 proteins, which are most highly affected by MWCNT and TiO2-NB, respectively. These proteins may be responsible for specific response of cells to the nanoparticles. Further 14 reported proteins are affected by either of the two nanoparticles and they are probably related to nonspecific toxic response of the cells. CONCLUSION: The similarity methods proposed in this paper may be useful in the management and visualization of the large amount of data generated by proteomics technologies. PMID- 27559001 TI - Generation of Multilayered 3D Structures of HepG2 Cells Using a Bio-printing Technique. AB - Background/Aims: Chronic liver disease is a major widespread cause of death, and whole liver transplantation is the only definitive treatment for patients with end-stage liver diseases. However, many problems, including donor shortage, surgical complications and cost, hinder their usage. Recently, tissue-engineering technology provided a potential breakthrough for solving these problems. Three dimensional (3D) printing technology has been used to mimic tissues and organs suitable for transplantation, but applications for the liver have been rare. Methods: A 3D bioprinting system was used to construct 3D printed hepatic structures using alginate. HepG2 cells were cultured on these 3D structures for 3 weeks and examined by fluorescence microscopy, histology and immunohistochemistry. The expression of liverspecific markers was quantified on days 1, 7, 14, and 21. Results: The cells grew well on the alginate scaffold, and liver-specific gene expression increased. The cells grew more extensively in 3D culture than two-dimensional culture and exhibited better structural aspects of the liver, indicating that the 3D bioprinting method recapitulates the liver architecture. Conclusions: The 3D bioprinting of hepatic structures appears feasible. This technology may become a major tool and provide a bridge between basic science and the clinical challenges for regenerative medicine of the liver. PMID- 27559002 TI - Analysis of users and reasons for use of a physician-on-call service in an Italian local health unit. AB - BACKGROUND: In recent years, several countries have proposed changes to primary care organisation. OBJECTIVE: Our study investigated the characteristics of 'physician-on-call' usage in a local health unit of Lombardy (ASL MI1). METHODS: We analysed the incoming calls to the Operative Medical Central Station and collected the user characteristics, the call reasons and the outcomes from 1 October to 31 December 2012. Then, we randomly extracted 10% of the call sample from this period. We focused on two outputs: telephone advice (TA) and emergency department referral. We fit a logistic regression model to identify potential predictors of these outputs. RESULTS: In total, we evaluated 2146 calls. Women made most of the calls. Older age was associated with the referral to emergency care [adjusted odds ratio (aOR) 3.1], while paediatric calls were associated with TA (aOR 1.9). Information requests were related to TA (aOR 2.3), while cardiovascular symptoms (aOR 3.5), pain (aOR 2.6) and traumas (aOR 4.7) were linked to emergency care. CONCLUSIONS: Our study outlined the increasing use of TA, particularly for calls regarding paediatric patients. In contrast, calls for elderly patients were more frequently referred to emergency care. These findings led to the implementation of an age-targeted educational programme. Overall, our observations highlighted that women used the physician-on-call service more frequently than men. Furthermore, some reasons for calling were significantly associated with emergency care. PMID- 27559004 TI - Treatment of End-stage Kidney Failure without Renal Replacement Therapy. AB - For the majority of patients with end-stage kidney failure (ESKF) replacement of excretory renal function by dialysis or transplantation (RRT) can extend life and alleviate symptoms. Historically, the availability of RRT has been insufficient and this remains the case for much of the world. However, RRT is now widely available in healthcare systems of higher income countries. Increasing numbers of elderly patients are developing ESKF. RRT in this population is largely by dialysis, comorbidity is high and life expectancy short. Evidence of effectiveness coupled with the burden of treatment among these individuals has raised concerns that health services in high-income countries may have moved from an era of unmet need into one of potential over-treatment. Alongside the requirement to make treatment more patient-centered, this has driven the development of comprehensive conservative care as an alternative approach for older comorbid individuals with ESKF, with the potential for acceptable symptom control and reduced treatment burden. This paper provides a largely UK perspective on treating ESKF without RRT. Emphasis is on the need for high quality evidence to inform treatment decisions. Complexities of defining, delivering and improving treatment of ESKF without dialysis care are explored. Quantitative and qualitative evidence are summarized and the relationship with palliative and terminal care examined. A framework is suggested for classifying management of ESKF and recommendations made to improve delivery of nondialysis care in the future. For patients with a poor prognosis, such treatment may not result in significantly different survival or quality of life when compared with dialysis. There is a key need to generate the best possible evidence of person centered health outcomes associated with the various treatment options for ESKF and to present this to patients in a balanced, personalized way that allows them to make the treatment decision most appropriate for them. PMID- 27559003 TI - P2X7 receptor-dependent tuning of gut epithelial responses to infection. AB - Infection and injury of the gut are associated with cell damage and release of molecules such as extracellular adenosine 5'-triphosphate (ATP), which is recognised by the purinergic P2X7 receptor (P2X7R). P2X7R is widely expressed in the gut by antigen-presenting cells (APCs) and epithelial cells, but the role of the P2X7R on epithelial cells is poorly understood. We investigated P2X7R in intestinal epithelium in vitro and in vivo using two model infections, Toxoplasma gondii and Trichinella spiralis. Lipopolysaccharide and ATP treatment of intestinal epithelial cells and infection with T. gondii in vitro did not promote inflammasome-associated interleukin-1beta (IL-1beta) or IL-18 secretion, but promoted C-C motif chemokine ligand 5 (CCL5), tumour necrosis factor-alpha and IL 6 production that were significantly reduced when the P2X7R was blocked. Similarly, in vivo, infection with either T. spiralis or T. gondii induced rapid upregulation of epithelial CCL5 in wild-type (wild-type (WT)) mice that was significantly reduced in P2X7R-/- littermate controls. The effects of reduced epithelial CCL5 were assayed by investigating recruitment of dendritic cells (DCs) to the epithelium. Infection induced a rapid recruitment of CD11c+CD103+ DC subsets into the epithelial layer of WT mice but not P2X7R-/- mice. In vitro chemotaxis assays and bone marrow chimeras demonstrated the importance of epithelial P2X7R in DC recruitment. P2X7R signalling in epithelial cells mediates chemokine responses to promote initiation of host immunity to infection. PMID- 27559005 TI - Pediatric Patient Blood Management Programs: Not Just Transfusing Little Adults. AB - Red blood cell transfusions are a common life-saving intervention for neonates and children with anemia, but transfusion decisions, indications, and doses in neonates and children are different from those of adults. Patient blood management (PBM) programs are designed to assist clinicians with appropriately transfusing patients. Although PBM programs are well recognized and appreciated in the adult setting, they are quite far from standard of care in the pediatric patient population. Adult PBM standards cannot be uniformly applied to children, and there currently is significant variation in transfusion practices. Because transfusing unnecessarily can expose children to increased risk without benefit, it is important to design PBM programs to standardize transfusion decisions. This article assesses the key elements necessary for a successful pediatric PBM program, systematically explores various possible pediatric specific blood conservation strategies and the current available literature supporting them, and outlines the gaps in the evidence suggesting need for further/improved research. Pediatric PBM programs are critically important initiatives that not only involve a cooperative effort between pediatric surgery, anesthesia, perfusion, critical care, and transfusion medicine services but also need operational support from administration, clinical leadership, finance, and the hospital information technology personnel. These programs also expand the scope for high-quality collaborative research. A key component of pediatric PBM programs is monitoring pediatric blood utilization and assessing adherence to transfusion guidelines. Data suggest that restrictive transfusion strategies should be used for neonates and children similar to adults, but further research is needed to assess the best oxygenation requirements, hemoglobin threshold, and transfusion strategy for patients with active bleeding, hemodynamic instability, unstable cardiac disease, and cyanotic cardiac disease. Perioperative blood management strategies include minimizing blood draws, restricting transfusions, intraoperative cell salvage, acute normovolemic hemodilution, antifibrinolytic agents, and using point-of-care tests to guide transfusion decisions. However, further research is needed for the use of intravenous iron, erythropoiesis-stimulating agents, and possible use of whole blood and pathogen inactivation. There are numerous areas where newly formed collaborations could be used to investigate pediatric transfusion, and these studies would provide critical data to support vital pediatric PBM programs to optimize neonatal and pediatric care. PMID- 27559006 TI - Current Status of Platelet Transfusion in Pediatric Patients. AB - Outside the neonatal period, most platelets that are transfused to pediatric patients are given to those who are thrombocytopenic secondary to malignancy and associated therapy and/or hematopoietic progenitor cell transplant, or to those with significant bleeding associated with surgery, especially cardiac surgery. Indications for platelet transfusion, doses, and other practices for children largely mimic adult platelet transfusion protocols because there are few pediatric-specific studies in this area. Pediatric platelet transfusion practices would benefit from focused pediatric research. The appropriate indications and doses for platelet transfusions in oncology, hematopoietic progenitor cell transplant, and cardiac surgery patients need to be determined. PMID- 27559007 TI - Risk factors for recurrence of borderline ovarian tumours: A tertiary centre experience. AB - The aim of this study was to evaluate the risk factors for recurrence of borderline ovarian tumours. This study investigated 127 women who were finally diagnosed with borderline epithelial ovarian tumours. Most of them were diagnosed in stage I (83.4%). With a median follow-up of 81.8 months (range: 14-205), the median time to recurrence was 22.4 months (range: 3-74). Five-year recurrence free survival (RFS) and overall survival (OS) rates were 85.8% and 97.6%, respectively. In multivariate analysis, invasive implants and fertility-sparing surgery were found to be independent prognostic factors for 5-year RFS. Overall, 20 patients (15.7%) experienced relapse within the observation period. Although there is no consensus about high-risk category of borderline ovarian tumours, invasive implants and conservative surgery were closely related to the recurrence. Patients presenting these risk factors should undergo closer follow up. PMID- 27559008 TI - Low ADAMTS-13 activity and the risk of coronary heart disease - a prospective cohort study: the Rotterdam Study. AB - : Essentials An association between ADAMTS-13 and coronary heart disease (CHD) has been suggested. 5688 participants >= 55 years from the Rotterdam Study without a history of CHD were included. Over a median follow-up time of 9.7 years, 456 individuals suffered from CHD. Low ADAMTS-13 activity was associated with an increased CHD risk. SUMMARY: Background The metalloprotease ADAMTS-13 cleaves high-molecular-weight von Willebrand factor multimers into smaller, less procoagulant forms. Low ADAMTS-13 activity is associated with an increased risk of ischemic stroke but its pathogenic role in coronary heart disease (CHD) is unclear. Objectives We aimed to determine the association between ADAMTS-13 activity and the risk of CHD in a large prospective population-based cohort study. Methods A total of 5688 participants of the Rotterdam Study, a population based cohort study involving individuals aged >= 55 years without a history of CHD, were included. ADAMTS-13 activity was measured by the FRETS-VWF73 assay and VWF:Ag levels by ELISA. We assessed the association between ADAMTS-13 activity, VWF:Ag levels and CHD using Cox proportional hazard regression analysis, adjusting for cardiovascular risk factors. Results Over a median follow-up time of 9.7 years, 456 individuals suffered from CHD. A low ADAMTS-13 activity (quartile 1) was associated with an increased CHD risk (HR 1.42, 95% CI 1.07 1.89) compared with the reference highest quartile. Conclusions Low ADAMTS-13 activity is associated with an increased risk of CHD in the elderly, independently of VWF and established cardiovascular risk factors. PMID- 27559009 TI - Genetics and pathophysiology of granulomatosis with polyangiitis (GPA) and its main autoantigen proteinase 3. AB - Granulomatosis with polyangiitis (GPA) is a severe autoimmune disease and one of the small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although its etiology and pathophysiology are still widely unknown, it is accepted that infections, environmental factors, epigenetic modifications, and a genetic predisposition provide the basis for this systemic disorder. GPA typically evolves into two phases: an initial phase characterized by ear, nose and throat (ENT) manifestations, such as chronic sinusitis and otitis, ulceration of the oral cavity and pharynx, as well as pulmonary nodules and a severe generalized phase, defined by the occurrence of rapidly progressive glomerulonephritis, pulmonary hemorrhage, and arthritis. ANCAs, directed against the neutrophilic enzymes proteinase 3 and myeloperoxidase, are present in up to 90% of the affected patients in the systemic phase. As the humoral immunity is predominantly directed against neutrophilic antigens, it is apparent that neutrophils play a critical role in GPA both as target and effector cells. Although GPA pathogenesis is not well known, some susceptibility genes and loci have been identified by candidate gene approaches, genome-wide association studies, and meta-analyses, as well as familial association studies. Such genes are CTLA4, PTPN22, COL11A2, SERPINA1, and the MHC class II gene cluster. This review highlights the clinical, pathophysiological, and genetic background of GPA and aims to give an overview of recent efforts to identify GPA susceptibility genes. We point out the genetic basis of the main autoantigen PR3 and why it is so difficult to establish a murine GPA model. PMID- 27559011 TI - Patterning nanofibrils through the templated growth of multiple modified amyloid peptides. AB - There has been considerable interest in the patterning of functionalized nanowires because of the potential applications of these materials to the construction of nanodevices. A variety of biomolecular building blocks containing amyloid peptides have been used to functionalize nanowires. However, the patterning of self-assembled nanowires can be challenging because of the difficulties associated with controlling the self-assembly of these functionalized building blocks. Herein, we present a versatile approach for the patterning of nanowires based on the combination of templated fibril growth with a versatile functionalization method using our structure-controllable amyloid peptides (SCAPs). Using this approach, we have succeeded in the formation of multi-type nanowires with tandem domain structures in high yields. Given that the mixing-SCAP method can lead to the formation of tandem fibrils, it is noteworthy that our method allowed us to control the initiation of fibril formation from the gold nanoparticles, which were attached to a short fibril as initiation points. This approach could be used to prepare a wide variety of fibril patterns, and therefore holds great potential for the development of novel self-assembled nanodevices. PMID- 27559012 TI - Differential responses of the vasotocin 1a receptor (V1aR) and osmoreceptors to immobilization and osmotic stress in sensory circumventricular organs of the chicken (Gallus gallus) brain. AB - Past studies have shown that the avian vasotocin 1a receptor (V1aR) is involved in immobilization stress. It is not known whether the receptor functions in osmotic stress, and if sensory circumventricular organs may be involved. An experiment was designed with four treatment groups including a 1h immobilization acute stress (AS) group, an unstressed acute control (AC), a third given an intraperitoneal (ip) hypertonic saline injection (HS) and isotonic saline controls (IC) administered ip. One set of chick brains was perfused for immunohistochemistry while a second was sampled for quantitative RT-PCR. Plasma corticosterone (CORT) and arginine vasotocin (AVT) concentrations were significantly increased in the immobilized and hypertonic saline groups (p<0.01) compared to controls. Intense staining of the V1aR occurred throughout the organum vasculosum of the lamina terminalis (OVLT) and subseptal organ (SSO)/subfornical organ (SFO). The immunostaining allowed the boundaries of the two circumventricular organs (CVOs) to be described for the first time in avian species. Both treatment groups showed marked morphological changes in glia within the OVLT and SSO/SFO. The avian V1aR, angiotensin II type 1 receptor (AT1R), and transient receptor potential vanilloid receptor 1 (TRPV1) mRNA levels were increased in the SSO/SFO in hypertonic saline treated birds compared to isotonic controls. In contrast, the latter two genes (AT1R and TRPV1) were significantly decreased in the OVLT of birds subjected to hyperosmotic stress, while all three genes were significantly up-regulated after immobilization. Taken together, results show a possible differential function for the same receptors in two anatomically adjacent CVOs. PMID- 27559010 TI - Werner syndrome through the lens of tissue and tumour genomics. AB - Werner syndrome (WS) is the canonical adult human progeroid ('premature aging') syndrome. Patients with this autosomal recessive Mendelian disorder display constitutional genomic instability and an elevated risk of important age associated diseases including cancer. Remarkably few analyses of WS patient tissue and tumors have been performed to provide insight into WS disease pathogenesis or the high risk of neoplasia. We used autopsy tissue from four mutation-typed WS patients to characterize pathologic and genomic features of WS, and to determine genomic features of three neoplasms arising in two of these patients. The results of these analyses provide new information on WS pathology and genomics; provide a first genomic characterization of neoplasms arising in WS; and provide new histopathologic and genomic data to test several popular models of WS disease pathogenesis. PMID- 27559013 TI - Trans-astaxanthin attenuates lipopolysaccharide-induced neuroinflammation and depressive-like behavior in mice. AB - Mounting evidence supports that inflammation and increased cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. Trans-astaxanthin has anti-inflammatory and antioxidative activity, also has the ability to cross the blood-brain barrier in rodents. Here, we investigated the effects of trans-astaxanthin on lipopolysaccharide (LPS)-induced depressive-like behavior in mice. In both the forced swimming test (FST) and tail suspension test (TST), the immobility time was increased when mice were administrated with a single dose of LPS (0.83mg/kg, i.p.). However, this alteration can be reversed by pretreatment of trans-astaxanthin at doses of 20, 40 and 80mg/kg (p.o.) for 7 days. Further neurochemical assays suggested that LPS induced overexpression of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF alpha) in the hippocampus and the prefrontal cortex (PFC) can also be reversed by trans-astaxanthin treatment. Moreover, trans-astaxanthin at 80mg/kg was demonstrated to effectively antagonize iNOS, nNOS and COX-2 expression, both at mRNA and protein levels, nitric oxide (NO) levels, via regulating NF-kappaB in the hippocampus and PFC. Taken together, trans-astaxanthin may serve as an effective therapeutic agent for LPS-induced depressive-like behavior via its potent anti-inflammatory property. PMID- 27559014 TI - Neutrophil gelatinase-associated lipocalin as a diagnostic marker of acute kidney injury in pre-eclampsia. AB - AIM: Neutrophil gelatinase-associated lipocalin (NGAL) is an emerging biomarker for early diagnosis of acute kidney injury (AKI). This study investigated the use of urinary NGAL as a marker of AKI in women with pre-eclampsia. METHODS: Urine and serum samples were collected over 24 h from 78 healthy and 109 pre-eclamptic women, with baseline samples taken at admission to the maternity unit; NGAL was assayed in serial urine samples. RESULTS: Baseline neutrophil gelatinase associated lipocalin did not differ significantly between women who were healthy, those with pre-eclampsia, or with AKI (P = 0.55 for trend). When the pre eclamptic group was divided into those with eclampsia (median, 60.5 ng/mL; IQR, 23.4-173 ng/mL; n = 19), uncomplicated pre-eclampsia (median, 18.8 ng/mL; IQR, 7.5-52.8 ng/mL; n = 48; P < 0.05 vs eclampsia), imminent eclampsia (median, 30.7 ng/mL; IQR, 13.9-49.3 ng/mL; n = 22) and pre-eclampsia with acute kidney injury (median, 60.3 ng/mL; IQR, 23.5-159 ng/mL, n = 14), however, NGAL level did differ. On multivariate regression analysis, the only significant correlate of NGAL level was the presence of eclampsia (beta = 0.22, P < 0.05). On receiver operating characteristic curve analysis, baseline NGAL did not discriminate between subjects with or without AKI (area under the curve, 0.61; 95%CI: 0.43 0.78; P = 0.12). CONCLUSION: Neutrophil gelatinase-associated lipocalin level at baseline and over a 24-h period does not provide a suitable diagnostic test for AKI in pre-eclamptic subjects. PMID- 27559015 TI - Commentary on: The Rainbow Scale for Assessing Breast Ptosis: Validation of Three Different Views. PMID- 27559016 TI - Investigation of the inhibitory properties of some phenolic standards and bee products against human carbonic anhydrase I and II. AB - Polyphenols are important secondary products of plants with the potential to inhibit carbonic anhydrases. The aim of this study was to investigate the inhibition effects of various phenolic standards, honey, propolis, and pollen species on human carbonic anhydrase I and II. The inhibition values (IC50) of the phenolics (gallic acid, protocatechuic acid, quercetin, catechin, tannic acid, and chrysin) ranged from 0.009 to 0.32 MUg/mL, tannic acid emerging as the best inhibitor. The inhibition values of three different types of honey, heather, rhododendron, and chestnut ranged between 2.32 and 25.10 MUg/mL, the chestnut honeys exhibiting the best inhibition. The ethanolic extracts of pollen and propolis exhibited good inhibitory properties, with IC50 values between 0.486 and 3.320 MUg/mL. In order to evaluate the phenolic composition of bee products, phenolic profiles and total phenolic contents (TFC) were also measured. The inhibition ranking among the natural products studied was phenolic standards > propolis > pollen > honeys, and inhibition was related to TFC. PMID- 27559017 TI - Synthesis of Optically Pure 3,3'-Disubstituted-1,1'-Bi-6-Methoxy-2-Phenol (BIPhOL) Derivatives via Diastereomeric Resolution. AB - A new protocol for the enantioselective synthesis of 3,3'-disubstituted-1,1'-bi-6 methoxy-2-phenol (BIPhOL) derivatives is described. Diastereomeric resolution of racemic BIPhOL boronic acid using a boronic acid moiety as a resolving group generated two diastereomers and subsequent Suzuki-Miyaura coupling reaction of the resulting diastereomers with aryl halides provided BIPhOL derivatives without any loss of enantioselectivity. In addition, the absolute stereochemistry of chiral BIPhOL was determined by comparison of the optical rotation with the reported value. PMID- 27559019 TI - Dietary patterns, overweight and obesity from 1961 to 2011 in the socioeconomic and political context of Argentina. AB - To analyse the changes in eating patterns in Argentina from 1961 to 2011, and to assess changes in overweight and obesity in their socioeconomic and political context, we performed a hierarchical cluster analysis. We used the information from Food Balance Sheets of the United Nations Food and Agriculture Organisation to identify dietary patterns of apparent consumption. Years were grouped into five patterns. The food group with the highest apparent consumption was cereals (30% of total kcal/person/day) although this decreased slightly. Meats were second and their contribution decreased by 12%. The following foods contribution increased during the period: Sugar and milk by 2% and vegetable oils by 6%. The changes observed in the number of kcal/person/day were in line with changes in real wage, and coincided with economic and political crises that Argentina experienced during that period. Changes in eating patterns allow us to interpret that they relate to the increase in overweight and obesity. PMID- 27559018 TI - Forging the ring: from fungal septins' divergent roles in morphology, septation and virulence to factors contributing to their assembly into higher order structures. AB - Septins are a conserved family of GTP-binding proteins that are distributed across different lineages of the eukaryotes, with the exception of plants. Septins perform a myriad of functions in fungal cells, ranging from controlling morphogenetic events to contributing to host tissue invasion and virulence. One key attribute of the septins is their ability to assemble into heterooligomeric complexes that organizse into higher order structures. In addition to the established role of septins in the model budding yeast, Saccharomyces cerevisiae, their importance in other fungi recently emerges. While newer roles for septins are being uncovered in these fungi, the mechanism of how septins assemble into a complex and their regulation is only beginning to be comprehended. In this review, we summarize recent findings on the role of septins in different fungi and focus on how the septin complexes of different fungi are organized in vitro and in vivo. Furthermore, we discuss on how phosphorylation/dephosphorylation can serve as an important mechanism of septin complex assembly and regulation. PMID- 27559020 TI - A rare case of blastic plasmacytoid dendritic cell neoplasm with deletion 7q.31, in the setting of heavy pre-treatment with alkylating chemotherapy. AB - Blastic plasmacytoid dendritic cell neoplasm is rare myeloid malignancy clinically characterized by non-pruritic, violaceous and papulo-nodular skin lesions, together with bone marrow and lymph node involvement. Histologically, there is infiltration of dermis by neoplastic mono-nuclear CD4, CD56, CD123 co expressing cells with epidermal sparing. Most commonly blastic plasmacytoid dendritic cell neoplasm presents as a de-novo condition, and treatment-related blastic plasmacytoid dendritic cell neoplasm is a rare phenomenon. Due to rarity of the disease, there is no established standard of care treatment. Both acute myeloid leukemia and acute lymphoid leukemia type induction regimens have been used for treatment of blastic plasmacytoid dendritic cell neoplasm, with initial response rate of 50%-80%. We present a rare case of therapy-associated blastic plasmacytoid dendritic cell neoplasm in a patient with remote history alkylating agent systemic therapy. A lag period of five to seven years and presence of deletion 7q.31 seen in bone marrow biopsy specimen in our patient are consistent with a likely therapy-associated etiology of his blastic plasmacytoid dendritic cell neoplasm. PMID- 27559021 TI - A Bayesian response-adaptive trial in tuberculosis: The endTB trial. AB - PURPOSE: To evaluate the use of Bayesian adaptive randomization for clinical trials of new treatments for multidrug-resistant tuberculosis. METHODS: We built a response-adaptive randomization procedure, adapting on two preliminary outcomes for tuberculosis patients in a trial with five experimental regimens and a control arm. The primary study outcome is treatment success after 73 weeks from randomization; preliminary responses are culture conversion at 8 weeks and treatment success at 39 weeks. We compared the adaptive randomization design with balanced randomization using hypothetical scenarios. RESULTS: When we compare the statistical power under adaptive randomization and non-adaptive designs, under several hypothetical scenarios we observe that adaptive randomization requires fewer patients than non-adaptive designs. Moreover, adaptive randomization consistently allocates more participants to effective arm(s). We also show that these advantages are limited to scenarios consistent with the assumptions used to develop the adaptive randomization algorithm. CONCLUSION: Given the objective of evaluating several new therapeutic regimens in a timely fashion, Bayesian response-adaptive designs are attractive for tuberculosis trials. This approach tends to increase allocation to the effective regimens. PMID- 27559022 TI - Adult patient perspectives on clinical trial result reporting: A survey of cancer patients. AB - BACKGROUND: The provision of study results to research participants is supported by pediatric and adult literature. This study assessed adult cancer patient preferences surrounding aggregate result disclosure to study participants. METHODS: A 46-item questionnaire was given to 250 adult cancer patients who had participated in oncology trials at a single center. Respondents answered questions surrounding their preferences for timing, content, and modality of communication for dissemination of study results. RESULTS: Questionnaire completion rate was 76% (189/250). Most patients (92%) strongly felt a right to know study results. Patients preferred result dissemination via letter for trials with positive outcomes, but preferred in-person clinic visits for negative outcomes. Despite this, a majority of participants (59%) found letters acceptable to inform participants of negative results. Only a minority (36%) of the participants found Internet-based disclosure acceptable for negative trial results. Unfortunately, very few patients (8%) recalled having received the results for a study they participated in, and of these patients, less than half fully understood the results they were given. CONCLUSION: Most clinical trial participants feel they have a right to study result disclosure, regardless of trial outcome. In-person visits are preferred for negative results, but more feasible alternatives such as letters were still acceptable for the majority of participants. However, Internet-based disclosure was not acceptable to most participants in oncology trials. Time and cost allocations for result disclosure should be considered during grant and ethics board applications, and clear guidelines are required to help researchers share the results with patients. PMID- 27559023 TI - Massive irreparable rotator cuff tear and associated deltoid tear. Does the reverse shoulder arthroplasty and deltoid repair be a possible option of treatment? AB - BACKGROUND AND PURPOSE: Rupture of the anterior and middle deltoid muscle associated with rotator cuff tear arthropathy (RCA) could result in a definitive loss of shoulder function. The purpose of this study was to evaluate clinical outcomes after a concomitant reverse shoulder arthroplasty (RSA) and deltoid repair under these circumstances. MATERIALS AND METHODS: Between 2006 and 2012, 18 consecutive patients with a mean age of 69.7 years, affected by massive irreparable rotator cuff tear and associated dehiscence or rupture of anterior and middle deltoid muscle underwent this operation through a modified anterosuperior approach. Four patients referred a previous shoulder surgery and deltoid tear was iatrogenic. The other 14 cases had an attritional deltoid tears. The average follow-up was 64 months (range 25-121 months). RESULTS: The mean active anterior elevation passed from a preoperative mean of 53 +/- 9.1 (range 45 70) to 132.7 +/- 11.6 degrees (85-155 degrees ), active external rotation passed from a preoperative mean value of 22.4 +/- 3.6 degrees (range 18-26) to an average of 33.7 +/- 4.7 degrees (range 30-40 degrees ). Mean Constant score increased from 42 +/- 6.1 (range 31-51) pre-operatively to 72.3 +/- 8.2 (range 57 82) post-operatively. At final review, deltoid contour subjectively was satisfactory to all patients with no palpable defects. CONCLUSION: RSA associated with a repair of deltoid tear could be a viable surgical option in cases of tear involving the anterior and middle deltoid associated with a RCA. Patient with a preoperative chronic axillary nerve neuropathy associated with a deltoid muscle tear should be cautioned about the possibility of lower functional outcomes. PMID- 27559025 TI - A Family of Negative Regulators Targets the Committed Step of de Novo Fatty Acid Biosynthesis. AB - Acetyl-CoA carboxylase (ACCase) catalyzes the committed step of de novo fatty acid biosynthesis. In prokaryotes, green algae, and most plants, this enzyme is a heteromeric complex requiring four different subunits for activity. The plant complex is recalcitrant to conventional purification schemes and hence the structure and composition of the full assembly have been unclear. In vivo coimmunoprecipitation using subunit-specific antibodies identified a novel family of proteins in Arabidopsis thaliana annotated as biotin/lipoyl attachment domain containing (BADC) proteins. Results from yeast two-hybrid and coexpression in Escherichia coli confirmed that all three BADC isoforms interact with the two biotin carboxyl carrier protein (BCCP) isoforms of Arabidopsis ACCase. These proteins resemble BCCP subunits but are not biotinylated due to a mutated biotinylation motif. We demonstrate that BADC proteins significantly inhibit ACCase activity in both E. coli and Arabidopsis. Targeted gene silencing of BADC isoform 1 in Arabidopsis significantly increased seed oil content when normalized to either mass or individual seed. We conclude the BADC proteins are ancestral BCCPs that gained a new function as negative regulators of ACCase after initial loss of the biotinylation motif. A functional model is proposed. PMID- 27559026 TI - Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans. AB - Although a number of drugs have been developed for the treatment and prevention of human immunodeficiency virus (HIV) infection, it has proven difficult to optimize the drug and dosage parameters. The vaginal tissue, comprised of epithelial, stromal and blood compartments presents a complex system which challenges evaluation of drug kinetics solely through empirical effort. To provide insight into the underlying processes, mathematical modeling and computational simulation have been applied to the study of retroviral microbicide pharmacokinetics. Building upon previous pioneering work that modeled the delivery of Tenofovir (TFV) via topical delivery to the vaginal environment, here we computationally evaluate the performance of the retroviral inhibitor dapivirine released from a microbicide gel. We adapt the TFV model to simulate the multicompartmental diffusion and uptake of dapivirine into the blood plasma and vaginal compartments. The results show that dapivirine is expected to accumulate at the interface between the gel and epithelium compartments due to its hydrophobic characteristics. Hydrophobicity also results in decreased diffusivity, which may impact distribution by up to 2 orders of magnitude compared to TFV. Maximum concentrations of dapivirine in the epithelium, stroma, and blood were 9.9e7, 2.45e6, and 119pg/mL, respectively. This suggests that greater initial doses or longer time frames are required to obtain higher drug concentrations in the epithelium. These observations may have important ramifications if a specific time frame is required for efficacy, or if a minimum/maximum concentration is needed in the mucus, epithelium, or stroma based on combined efficacy and safety data. PMID- 27559024 TI - Altered Transcription and Neofunctionalization of Duplicated Genes Rescue the Harmful Effects of a Chimeric Gene in Brassica napus. AB - Chimeric genes contribute to the evolution of diverse functions in plants and animals. However, new chimeric genes also increase the risk of developmental defects. Here, we show that the chimeric gene Brassica napus male sterile 4 (Bnams4b ) is responsible for genic male sterility in the widely used canola line 7365A (Bnams3 ms3ms4bms4b ). Bnams4b originated via exon shuffling ~4.6 million years ago. It causes defects in the normal functions of plastids and induces aborted anther formation and/or albino leaves and buds. Evidence of the age of the mutation, its tissue expression pattern, and its sublocalization indicated that it coevolved with BnaC9.Tic40 (BnaMs3). In Arabidopsis thaliana, Bnams4b results in complete male sterility that can be rescued by BnaC9.Tic40, suggesting that BnaC9.Tic40 might restore fertility through effects on protein level. Another suppressor gene, Bnams4a , rescues sterility by reducing the level of transcription of Bnams4b Our results suggest that Brassica plants have coevolved altered transcription patterns and neofunctionalization of duplicated genes that can block developmental defects resulting from detrimental chimeric genes. PMID- 27559028 TI - Bacteria in decomposing wood and their interactions with wood-decay fungi. AB - The fungal community within dead wood has received considerable study, but far less attention has been paid to bacteria in the same habitat. Bacteria have long been known to inhabit decomposing wood, but much remains underexplored about their identity and ecology. Bacteria within the dead wood environment must interact with wood-decay fungi, but again, very little is known about the form this takes; there are indications of both antagonistic and beneficial interactions within this fungal microbiome. Fungi are hypothesised to play an important role in shaping bacterial communities in wood, and conversely, bacteria may affect wood-decay fungi in a variety of ways. This minireview considers what is currently known about bacteria in wood and their interactions with fungi, and proposes possible associations based on examples from other habitats. It aims to identify key knowledge gaps and pressing questions for future research. PMID- 27559029 TI - Illustrating the Importance of Critical Epistemology to Realize the Promise of Occupational Justice. AB - This article argues that it is vital to embrace critical reflexivity to interrogate the epistemological beliefs and principles guiding occupation-based scholarship to move away from frameworks that are incongruent with calls for occupational justice. For this purpose, we describe an epistemic tension between the stated intentions to demonstrate that occupation-based work can be a means to create a more just society and the epistemological beliefs that have historically dominated occupation-based scholarship. To exemplify the potential implications of this tension, a critical analysis of Creswell's social justice/transformative design is presented, illustrating that work that expresses a commitment to social justice while relying on positivist/postpositivist assumptions often risks perpetuating injustices through neglecting their sociopolitical construction. Drawing upon critical social theory, we highlight how engagement with critical epistemological assumptions can facilitate addressing the sociopolitical "roots" of occupational injustices and highlight directions for social transformation. PMID- 27559027 TI - Taxonomic and predicted metabolic profiles of the human gut microbiome in pre Columbian mummies. AB - Characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. We characterized the gut microbiome of two pre-Columbian Andean mummies dating to the 10-15th centuries using 16S rRNA gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century AD pre-Columbian Andean mummy. Our previous study showed that the Clostridiales represented the majority of the bacterial communities in the mummified gut remains, but that other microbial communities were also preserved during the process of natural mummification, as shown with the metagenomics analyses. The gut microbiome of the other two mummies were mainly comprised by Clostridiales or Bacillales, as demonstrated with 16S rRNA gene amplicon sequencing, many of which are facultative anaerobes, possibly consistent with the process of natural mummification requiring low oxygen levels. Metagenome analyses showed the presence of other microbial groups that were positively or negatively correlated with specific metabolic profiles. The presence of sequences similar to both Trypanosoma cruzi and Leishmania donovani could suggest that these pathogens were prevalent in pre-Columbian individuals. Taxonomic and functional profiling of mummified human gut remains will aid in the understanding of the microbial ecology of the process of natural mummification. PMID- 27559030 TI - Clinical and Laboratory Evaluation of a New Specific Point-of-Care Test for Intact Proinsulin. AB - BACKGROUND: Intact proinsulin is a biomarker for pancreatic beta-cell dysfunction. In large prospective studies in nondiabetic subjects, elevated intact proinsulin predicted development of type 2 diabetes and/or macrovascular events up to 7 years in advance. This study was performed to evaluate a new semiquantitative lateral flow-based point-of-care rapid test (POCT) for elevated intact proinsulin (cutoff: 15 pmol/L). The test requires 10 uL of capillary whole blood, with visual readout after 5 minutes. It is best applied at 2 hours after a glucose challenge or a meal. METHODS: POCT results were obtained by health care professionals from 60 patients and healthy subject (33 female, 27 male, 28 type 2 diabetes, age: 53.6 +/- 12.3 years). An additional venous blood sample was obtained from all participants for measurement of intact proinsulin by means of a quantitative ELISA reference method (TecoMedical, Sissach, Switzerland). RESULTS: Elevated intact proinsulin levels (>15 pmol/L) were determined by the reference method in 26 participants, of whom 22 were also positive with the POCT (sensitivity: 85%). All 34 subjects with low intact proinsulin levels were tested negative by the POCT (specificity: 100%). CONCLUSIONS: The test successfully detected elevated postprandial intact proinsulin levels in 85% of the tested subjects and no false positive test result occurred. This POCT can therefore serve as a simple screening tool for identification of patients with prevalent beta-cell dysfunction, who are at high risk for development of type 2 diabetes and/or macrovascular events within the next 5-7 years. PMID- 27559031 TI - A Multicenter Evaluation of the Performance and Usability of a Novel Glucose Monitoring System in Chinese Adults With Diabetes. AB - OBJECTIVE: Flash glucose monitoring is a new glucose sensing technique that measures interstitial glucose levels for up to 14 days and does not require any calibration. The aim of this study is to evaluate the performance of the new system in Chinese patients with diabetes. METHODS: A multicenter, prospective, masked study was performed in a total of 45 subjects with diabetes. Subjects wore 2 sensors at the same time, for up to 14 days. The accuracy was evaluated against capillary blood glucose (BG) and venous Yellow Springs Instrument (YSI; Yellow Springs, OH) measurements. During all 14 days, subjects were asked to perform at least 8 capillary BG tests per day. Each subject attended 3 days of 8-hour clinic sessions to measure YSI and sensor readings every 15 minutes. RESULTS: Forty subjects had evaluable glucose readings, with 6687 of 6696 (99.9%) sensor and capillary BG pairs within consensus error grid zones A and B, including 5824 (87.0%) in zone A. The 6969 sensor and venous YSI pairs resulted in 6965 (99.9%) pairs within zones A and B, including 5755 (82.6%) in zone A. The sensor pairs with BG and YSI result in mean absolute relative difference (MARD) of 10.0% and 10.7%, respectively. Overall between-sensor coefficient of variation (CV) was 8.0%, and the mean lag time was 3.1 (95% confidence interval 2.54 to 4.29) minutes. CONCLUSIONS: The system works well for people with diabetes in China, and it is easy to wear and use. PMID- 27559032 TI - Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. AB - It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure. PMID- 27559034 TI - An 11-Year-Old Boy With Sudden-Onset Abdominal Pain. PMID- 27559035 TI - Glycosylphosphatidylinositol (GPI) Modification Serves as a Primary Plasmodesmal Sorting Signal. AB - Plasmodesmata (Pd) are membranous channels that serve as a major conduit for cell to-cell communication in plants. The Pd-associated beta-1,3-glucanase (BG_pap) and CALLOSE BINDING PROTEIN1 (PDCB1) were identified as key regulators of Pd conductivity. Both are predicted glycosylphosphatidylinositol-anchored proteins (GPI-APs) carrying a conserved GPI modification signal. However, the subcellular targeting mechanism of these proteins is unknown, particularly in the context of other GPI-APs not associated with Pd Here, we conducted a comparative analysis of the subcellular targeting of the two Pd-resident and two unrelated non-Pd GPI-APs in Arabidopsis (Arabidopsis thaliana). We show that GPI modification is necessary and sufficient for delivering both BG_pap and PDCB1 to Pd Moreover, the GPI modification signal from both Pd- and non-Pd GPI-APs is able to target a reporter protein to Pd, likely to plasma membrane microdomains enriched at Pd As such, the GPI modification serves as a primary Pd sorting signal in plant cells. Interestingly, the ectodomain, a region that carries the functional domain in GPI APs, in Pd-resident proteins further enhances Pd accumulation. However, in non-Pd GPI-APs, the ectodomain overrides the Pd targeting function of the GPI signal and determines a specific GPI-dependent non-Pd localization of these proteins at the plasma membrane and cell wall. Domain-swap analysis showed that the non-Pd localization is also dominant over the Pd-enhancing function mediated by a Pd ectodomain. In conclusion, our results indicate that segregation between Pd- and non-Pd GPI-APs occurs prior to Pd targeting, providing, to our knowledge, the first evidence of the mechanism of GPI-AP sorting in plants. PMID- 27559037 TI - Light Refraction by Water as a Rationale for the Poggendorff Illusion. AB - The Poggendorff illusion in its classical form of parallel lines interrupting a transversal is viewed from the perspective of being related to the everyday experience of observing the light refraction in water. It is argued that if one considers a transversal to be a light ray in air and the parallel lines to form an occluding strip of a medium with the refractive index being between that of air and water, then one should be able to account, both qualitatively and quantitatively, for most of the features associated with the Poggendorff illusion. Statistical treatment of the visual experiments conducted with seven participants, each analyzing 50 configurations having different intercepting angles and strip widths, resulted in the effective refractive index of the occluding strip N = 1.13 +/- 0.15, which is sufficiently close to the average (between that of water and air) refractive index of ~1.17. It is further argued that the same mechanism can also be employed to account for many variants of the Poggendorff illusion, including the corner-Poggendorff pattern, as well as for the Hering illusion. PMID- 27559036 TI - SHORT HYPOCOTYL1 Encodes a SMARCA3-Like Chromatin Remodeling Factor Regulating Elongation. AB - In Arabidopsis (Arabidopsis thaliana), the UVR8-mediated signaling pathway is employed to attain UVB protection and acclimation to deal with low-dosage UVB (LDUVB)-induced stresses. Here, we identified SHORT HYPOCOTYL1 (SH1) in cucumber (Cucumis sativus), which regulates LDUVB-dependent hypocotyl elongation by modulating the UVR8 signaling pathway. We showed that hypocotyl elongation in cucumbers carrying the recessive sh1 allele was LDUVB insensitive and that Sh1 encoded a human SMARCA3-like chromatin remodeling factor. The allele frequency and distribution pattern at this locus among natural populations supported the wild cucumber origin of sh1 for local adaptation, which was under selection during domestication. The cultivated cucumber carries predominantly the Sh1 allele; the sh1 allele is nearly fixed in the semiwild Xishuangbanna cucumber, and the wild cucumber population is largely at Hardy-Weinberg equilibrium for the two alleles. The SH1 protein sequence was highly conserved among eukaryotic organisms, but its regulation of hypocotyl elongation in cucumber seems to be a novel function. While Sh1 expression was inhibited by LDUVB, its transcript abundance was highly correlated with hypocotyl elongation rate and the expression level of cell-elongation-related genes. Expression profiling of key regulators in the UVR8 signaling pathway revealed significant differential expression of CsHY5 between two near isogenic lines of Sh1 Sh1 and CsHY5 acted antagonistically at transcriptional level. A working model was proposed in which Sh1 regulates LDUVB dependent hypocotyl elongation in cucumber through changing the chromatin states and thus the accessibility of CsHY5 in the UVR8 signaling pathway to promoters of LDUVB-responsive genes for hypocotyl elongation. PMID- 27559039 TI - Infertility and non-traditional families. PMID- 27559040 TI - Association study of two functional single nucleotide polymorphisms of neuropeptide y gene with multiple sclerosis. AB - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by brain inflammation, demyelination and axonal loss. Neuropeptide Y (NPY) has a critical role in the maintenance of homeostasis in the immune system and coping of stress condition. In the current study we analyzed 188 patients suffering from MS and 204 unrelated healthy controls for two functional single nucleotide polymorphisms (SNPs), NPY 20T>C (rs16139) and NPY -485T>C (rs16147) using PCR-RFLP and Mismatch PCR-RFLP methods. Our results demonstrated that homozygocity in the minor allele for NPY -485T>C polymorphism is associated with the MS risk in patients in compare with healthy controls (CC vs. TT, P=0.033; CC vs. TT+TC, P=0.02). In addition, by comparison with allele T, the frequency of NPY -485C allele was higher in cases than in control subjects and present increased risk of MS, but statistically significant was borderline (P=0.053). The stratification for disease progression revealed a significant difference in the allelic and genotypic distribution between subgroups of MS and controls. The frequency of the CC genotype and C allele was higher in the primary progressive MS patients when compared with control group (CC vs. TT, P=0.019; CC vs. TT+TC, P=0.008; C vs. T, P=0.022). In addition, the frequency of CC genotype was higher in the relapsing remitting MS patients when compared with control group (CC vs. TT, P=0.034; CC vs. TT+TC, P=0.016). Haplotype analysis demonstrated that the haplotype 3 (CT) is more common in RR MS (P=0.041), and PP MS (P=0.031) than control group. In conclusion, the obtained results demonstrate the probable role of NPY SNPs in susceptibility to MS within the Iranian population. PMID- 27559041 TI - Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. AB - BACKGROUND: Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. METHODS: In this prospective, randomized, double-blind, double-dummy, crossover pharmacodynamic study, aspirin-treated DM patients (n=50) with coronary artery disease were randomly assigned to receive prasugrel (60 mg loading dose [LD]/10 mg maintenance dose once daily) or ticagrelor (180 mg LD/90 mg maintenance dose twice daily) for 1 week. Pharmacodynamic assessments were conducted using 4 different assays, including VerifyNow P2Y12, vasodilator stimulated phosphoprotein, light transmittance aggregometry, and Multiplate, which allowed us to explore ADP- and non-ADP-induced (arachidonic acid-, collagen , thrombin receptor-activating, peptide-induced) platelet signaling pathways. The acute (baseline, 30 minutes, and 2 hours post-LD) and maintenance (1 week) effects of therapy were assessed. The primary end point of the study was the comparison of P2Y12 reaction units determined by VerifyNow P2Y12 at 1 week between prasugrel and ticagrelor. RESULTS: ADP- and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and maintenance dose. P2Y12 reaction units defined by VerifyNow were similar between prasugrel and ticagrelor at 30 minutes and 2 hours post-LD. At 1 week, P2Y12 reaction units were significantly lower with ticagrelor than with prasugrel (52 [32-72] versus 83 [63-103]; least-square means difference: -31; 95% confidence interval, -57 to -4; P=0.022; primary end point). Pharmacodynamic assessments measured by vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate were similar between prasugrel and ticagrelor at each time point, including at 1 week. Rates of high on-treatment platelet reactivity were similar between groups with all assays at all time points. CONCLUSIONS: In DM patients with coronary artery disease, ticagrelor exerts similar or greater inhibition of ADP-induced platelet reactivity in comparison with prasugrel in the acute and chronic phases of treatment, whereas the inhibition of measures of non-ADP-induced platelet reactivity was not significantly different between the 2 agents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01852214. PMID- 27559043 TI - Draft genome sequence and annotation of Lactobacillus acetotolerans BM-LA14527, a beer-spoilage bacteria. AB - Lactobacillus acetotolerans is a hard-to-culture beer-spoilage bacterium capable of entering into the viable putative nonculturable (VPNC) state. As part of an initial strategy to investigate the phenotypic behavior of L. acetotolerans, draft genome sequencing was performed. Results demonstrated a total of 1824 predicted annotated genes, with several potential VPNC- and beer-spoilage associated genes identified. Importantly, this is the first genome sequence of L. acetotolerans as beer-spoilage bacteria and it may aid in further analysis of L. acetotolerans and other beer-spoilage bacteria, with direct implications for food safety control in the beer brewing industry. PMID- 27559042 TI - Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation. AB - BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS: Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides. RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed. In addition, putative and novel glycosylation sites were detected. On enrichment for glycoproteins, peptides of the small leucine-rich proteoglycan decorin were identified consistently in the flowthrough. Of all ECM proteins identified, decorin was found to be the most fragmented. Within its protein core, 18 different cleavage sites were identified. In contrast, less cleavage was observed for biglycan, the most closely related proteoglycan. Decorin processing differed between human ventricles and atria and was altered in disease. The C terminus of decorin, important for the interaction with connective tissue growth factor, was detected predominantly in ventricles in comparison with atria. In contrast, atrial appendages from patients in persistent atrial fibrillation had greater levels of full-length decorin but also harbored a cleavage site that was not found in atrial appendages from patients in sinus rhythm. This cleavage site preceded the N-terminal domain of decorin that controls muscle growth by altering the binding capacity for myostatin. Myostatin expression was decreased in atrial appendages of patients with persistent atrial fibrillation and hearts of decorin null mice. A synthetic peptide corresponding to this decorin region dose dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts. CONCLUSIONS: This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors. PMID- 27559044 TI - Degradation and emission of carbonyl sulfide, an atmospheric trace gas, by fungi isolated from forest soil. AB - Soil is thought to be important both as a source and a sink of carbonyl sulfide (COS) in the troposphere, but the mechanism affecting COS uptake, especially for fungi, remains uncertain. Fungal isolates that were collected randomly from forest soil showed COS-degrading ability at high frequencies: 38 out of 43 isolates grown on potato dextrose agar showed degradation of 30 ppmv COS within 24 h. Of these isolates, eight degraded 30 ppmv of COS to below the detection limit within 2 h. These isolates also showed an ability to degrade COS included in ambient air (around 500 pptv) and highly concentrated (12 500 ppmv) level, even though the latter is higher than the lethal level for mammals. COS-degrading activity was estimated by using ergosterol as a biomass index for fungi. Trichoderma sp. THIF08 had the highest COS-degrading activity of all the isolates. Interestingly, Umbelopsis/Mortierella spp. THIF09 and THIF13 were unable to degrade 30 ppmv COS within 24 h, and actually emitted COS during the cultivation in ambient air. These results indicate a fungal contribution to the flux of COS between the terrestrial and atmospheric environments. PMID- 27559045 TI - Mincle Signaling Promotes Con A Hepatitis. AB - Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPbeta and hypoxia-inducible factor-1alpha (HIF-1alpha) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-kappabeta-related signaling intermediates C/EBPbeta and HIF-1alpha, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPbeta and HIF-1alpha reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. PMID- 27559046 TI - IgG Binding Characteristics of Rhesus Macaque FcgammaR. AB - Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions in many cases is known to rely heavily on the ability of Abs to interact with a set of Ab FcgammaR expressed on innate immune cells. Yet, despite their presumed functional importance, M. mulatta Ab receptors are largely uncharacterized, posing a fundamental limit to ensuring accurate interpretation and translation of results from studies in this model. In this article, we describe the binding characteristics of the most prevalent allotypic variants of M. mulatta FcgammaR for binding to both human and M. mulatta IgG of varying subclasses. The resulting determination of the affinity, specificity, and glycan sensitivity of these receptors promises to be useful in designing and evaluating studies of candidate vaccines and therapeutic Abs in this key animal model and exposes significant evolutionary divergence between humans and macaques. PMID- 27559047 TI - Lactic Acid Suppresses IL-33-Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1alpha-Dependent miR-155 Suppression. AB - Lactic acid (LA) is present in tumors, asthma, and wound healing, environments with elevated IL-33 and mast cell infiltration. Although IL-33 is a potent mast cell activator, how LA affects IL-33-mediated mast cell function is unknown. To investigate this, mouse bone marrow-derived mast cells were cultured with or without LA and activated with IL-33. LA reduced IL-33-mediated cytokine and chemokine production. Using inhibitors for monocarboxylate transporters (MCT) or replacing LA with sodium lactate revealed that LA effects are MCT-1- and pH dependent. LA selectively altered IL-33 signaling, suppressing TGF-beta-activated kinase-1, JNK, ERK, and NF-kappaB phosphorylation, but not p38 phosphorylation. LA effects in other contexts have been linked to hypoxia-inducible factor (HIF) 1alpha, which was enhanced in bone marrow-derived mast cells treated with LA. Because HIF-1alpha has been shown to regulate the microRNA miR-155 in other systems, LA effects on miR-155-5p and miR-155-3p species were measured. In fact, LA selectively suppressed miR-155-5p in an HIF-1alpha-dependent manner. Moreover, overexpressing miR-155-5p, but not miR-155-3p, abolished LA effects on IL-33 induced cytokine production. These in vitro effects of reducing cytokines were consistent in vivo, because LA injected i.p. into C57BL/6 mice suppressed IL-33 induced plasma cytokine levels. Lastly, IL-33 effects on primary human mast cells were suppressed by LA in an MCT-dependent manner. Our data demonstrate that LA, present in inflammatory and malignant microenvironments, can alter mast cell behavior to suppress inflammation. PMID- 27559048 TI - The DNA Damage Response Regulates RAG1/2 Expression in Pre-B Cells through ATM FOXO1 Signaling. AB - The recombination activating gene (RAG) 1 and RAG2 protein complex introduces DNA breaks at Tcr and Ig gene segments that are required for V(D)J recombination in developing lymphocytes. Proper regulation of RAG1/2 expression safeguards the ordered assembly of Ag receptors and the development of lymphocytes, while minimizing the risk for collateral damage. The ataxia telangiectasia mutated (ATM) kinase is involved in the repair of RAG1/2-mediated DNA breaks and prevents their propagation. The simultaneous occurrence of RAG1/2-dependent and independent DNA breaks in developing lymphocytes exposed to genotoxic stress increases the risk for aberrant recombinations. In this study, we assessed the effect of genotoxic stress on RAG1/2 expression in pre-B cells and show that activation of the DNA damage response resulted in the rapid ATM-dependent downregulation of RAG1/2 mRNA and protein expression. We show that DNA damage led to the loss of FOXO1 binding to the enhancer region of the RAG1/2 locus (Erag) and provoked FOXO1 cleavage. We also show that DNA damage caused by RAG1/2 activity in pre-B cells was able to downmodulate RAG1/2 expression and activity, confirming the existence of a negative feedback regulatory mechanism. Our data suggest that pre-B cells are endowed with a protective mechanism that reduces the risk for aberrant recombinations and chromosomal translocations when exposed to DNA damage, involving the ATM-dependent regulation of FOXO1 binding to the Erag enhancer region. PMID- 27559049 TI - Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis. AB - Helminthic infections modulate host immunity and may protect people in less developed countries from developing immunological diseases. In a murine colitis model, the helminth Heligmosomoides polygyrus bakeri prevents colitis via induction of regulatory dendritic cells (DCs). The mechanism driving the development of these regulatory DCs is unexplored. There is decreased expression of the intracellular signaling pathway spleen tyrosine kinase (Syk) in intestinal DCs from H. polygyrus bakeri-infected mice. To explore the importance of this observation, it was shown that intestinal DCs from DC-specific Syk(-/-) mice were powerful inhibitors of murine colitis, suggesting that loss of Syk was sufficient to convert these cells into their regulatory phenotype. DCs sense gut flora and damaged epithelium via expression of C-type lectin receptors, many of which signal through the Syk signaling pathway. It was observed that gut DCs express mRNA encoding for C-type lectin (CLEC) 7A, CLEC9A, CLEC12A, and CLEC4N. H. polygyrus bakeri infection downmodulated CLEC mRNA expression in these cells. Focusing on CLEC7A, which encodes for the dectin-1 receptor, flow analysis showed that H. polygyrus bakeri decreases dectin-1 expression on the intestinal DC subsets that drive Th1/Th17 development. DCs become unresponsive to the dectin-1 agonist curdlan and fail to phosphorylate Syk after agonist stimulation. Soluble worm products can block CLEC7A and Syk mRNA expression in gut DCs from uninfected mice after a brief in vitro exposure. Thus, downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. PMID- 27559050 TI - A Critical Role for P2X7 Receptor-Induced VCAM-1 Shedding and Neutrophil Infiltration during Acute Lung Injury. AB - Pulmonary neutrophils are the initial inflammatory cells that are recruited during lung injury and are crucial for innate immunity. However, pathological recruitment of neutrophils results in lung injury. The objective of this study is to determine whether the novel neutrophil chemoattractant, soluble VCAM-1 (sVCAM 1), recruits pathological levels of neutrophils to injury sites and amplifies lung inflammation during acute lung injury. The mice with P2X7 receptor deficiency, or treated with a P2X7 receptor inhibitor or anti-VCAM-1 Abs, were subjected to a clinically relevant two-hit LPS and mechanical ventilation-induced acute lung injury. Neutrophil infiltration and lung inflammation were measured. Neutrophil chemotactic activities were determined by a chemotaxis assay. VCAM-1 shedding and signaling pathways were assessed in isolated lung epithelial cells. Ab neutralization of sVCAM-1 or deficiency or antagonism of P2X7R reduced neutrophil infiltration and proinflammatory cytokine levels. The ligands for sVCAM-1 were increased during acute lung injury. sVCAM-1 had neutrophil chemotactic activities and activated alveolar macrophages. VCAM-1 is released into the alveolar airspace from alveolar epithelial type I cells through P2X7 receptor-mediated activation of the metalloproteinase ADAM-17. In conclusion, sVCAM-1 is a novel chemoattractant for neutrophils and an activator for alveolar macrophages. Targeting sVCAM-1 provides a therapeutic intervention that could block pathological neutrophil recruitment, without interfering with the physiological recruitment of neutrophils, thus avoiding the impairment of host defenses. PMID- 27559051 TI - Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development. AB - Autoimmune diseases are characterized by pathogenic immune responses to self antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self antigens develops and the contribution of self-memory to the development of lupus related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy. PMID- 27559052 TI - Class-Switch Recombination in the Absence of the IgH 3' Regulatory Region. AB - The ~28-kb 3' regulatory region (3'RR), which is located at the most distal 3' region of the Ig H chain locus, has multiple regulatory functions that control IgH expression, class-switch recombination (CSR), and somatic hypermutation. In this article, we report that deletion of the entire 3'RR in a mouse B cell line that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR. These data suggest that 3'RR is not absolutely required for CSR and, thus, is not essential for targeting activation-induced cytidine deaminase to S regions, as was suggested. Moreover, replacing 3'RR with a DNA fragment including only its four DNase I hypersensitive sites (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild type cells, suggesting that the four hypersensitive sites contain most of the CSR promoting functions of 3'RR. Stimulated cells express abundant germline transcripts, with the presence or absence of 3'RR, providing evidence that 3'RR has a role in promoting CSR that is unique from enhancing S region transcription. PMID- 27559054 TI - Pregnancy as protest in interwar British women's writing: an antecedent alternative to Aldous Huxley's Brave New World. AB - Accounts that take Aldous Huxley's Brave New World (1932) as representative of interwar reproductive dystopia fail to recognise that the novel expresses both an interest and an anxiety about the possibility of new reproductive technologies to transform sex, gender, and the family that were widely shared by writers in different genres and perhaps expressed best by those likely to be most affected: women. This article explores three earlier works-Charlotte Haldane's Man's World (1926), Vera Brittain's Halcyon, or the Future of Monogamy (1929), and Naomi Mitchison's Comments on Birth Control (1930)-in which pregnancy, instead of figuring as illness or debility, becomes a form of resistance to the status quo. These works engage with biomedicine, however, rather than abjuring it. Through a reading of these works, this article argues that the intersection of medical humanities and science fiction (SF) can enrich both: medical humanities can push SF to go beyond the canon, and SF can challenge any characterisation of literature in the medical humanities as purely fantastical by demonstrating how it responds to the hopes and anxieties of a particular time. PMID- 27559053 TI - Drug-Driven Synthetic Lethality: Bypassing Tumor Cell Genetics with a Combination of AsiDNA and PARP Inhibitors. AB - Purpose: Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are PARP inhibitors (PARPi), which trigger synthetic lethality in tumors with homologous recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and nonhomologous end joining, together with PARPi should allow bypassing the genetic restriction for PARPi efficacy.Experimental Design: We characterized the DNA repair inhibition activity of PARPi (olaparib) and AsiDNA by monitoring repair foci formation and DNA damage. We analyzed the cell survival to standalone and combined treatments of 21 tumor cells and three nontumor cells. In 12 breast cancer (BC) cell lines, correlation with sensitivity to each drug and transcriptome were statistically analyzed to identify resistance pathways.Results: Molecular analyses demonstrate that olaparib and AsiDNA respectively prevent recruitment of XRCC1 and RAD51/53BP1 repair enzymes to damage sites. Combination of both drugs increases the accumulation of unrepaired damage resulting in an increase of cell death in all tumor cells. In contrast, nontumor cells do not show an increase of DNA damage nor lethality. Analysis of multilevel omics data from BC cells highlighted different DNA repair and cell-cycle molecular profiles associated with resistance to AsiDNA or olaparib, rationalizing combined treatment. Treatment synergy was also confirmed with six other PARPi in development.Conclusions: Our results highlight the therapeutic interest of combining AsiDNA and PARPi to recapitulate synthetic lethality in all tumors independently of their HR status. Clin Cancer Res; 23(4); 1001-11. (c)2016 AACR. PMID- 27559055 TI - Zombie tapeworms in late capitalism: accelerating clinical and reproductive labour in Mira Grant's Parasitology Trilogy. AB - Biomedicine is increasingly shaped by the speculative economical values of neoliberal capitalism. A key feature of this new bioeconomical regime is the patenting and circulation of organisms and tissue samples, allowing rapid commercialisation of bacterial, animal and human biomedical materials. When thinking about this trend towards commercialisation, we must consider the ways by which biomedicine has been shaped by economics to better address these exploitative relationships between medical researchers and subjects. These fraught questions of agency and exploitation can be addressed through the concept of clinical labour, a term Melinda Cooper and Catherine Waldby coined to discuss embodied forms of labour, including surrogacy, clinical trials and tissue economies, that dominate the post-Fordist biomedical economy. As a genre that extrapolates from contemporary technoscientific practices, science fiction is uniquely positioned to explore the ethics of biomedical research in this neoliberal speculative economy. Science fiction can give human-like agency and affect to microbial, animal and alien life, allowing modified organisms to speak and interact with their creators. Creating these dialogues between commercialised organisms and biomedical researchers makes clear the connections between contemporary clinical practice and exploitative labour relations, illuminating the more troubling aspects of the new bioeconomy and imagining alternatives to this system. PMID- 27559056 TI - Whereto speculative bioethics? Technological visions and future simulations in a science fictional culture. AB - This article critically examines the development and current state of speculative bioethics (bioethics discourse concerned with future technologies) as reflecting an intensifying science fictionality, a cognitive/perceptual mode in which the imagined future begins to exert increasing degrees of influence on the present, culminating in a collapse of distance between the two. Future technologies thereby come to be viewed as generating practical ethical issues that need to be addressed well in advance of their arrival. Although this appears to be a prudent effort, it actually bypasses the present as a site of moral agency and locates ethics within a simulation of the imagined future. A constructive form of speculative bioethics must be able to critically assess visions of technological futures if it is to function as an ethics that is of and for the present. PMID- 27559057 TI - A Prospective, Randomized Trial of Routine Duplex Ultrasound Surveillance on Arteriovenous Fistula Maturation. AB - BACKGROUND AND OBJECTIVES: Use of arteriovenous fistulas, the most preferred type of access for hemodialysis, is limited by their high maturation failure rate. The aim of this study was to assess whether aggressive surveillance with routine duplex ultrasound and intervention can decrease the maturation failure rate of arteriovenous fistulas. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a single-center, parallel-group, randomized, controlled trial of patients undergoing autogenous arteriovenous fistula. Patients were randomly assigned (1:1) to either the routine duplex or selective duplex group. In the routine duplex group, duplex ultrasound and physical examination were performed 2, 4, and 8 weeks postoperatively. In the selective duplex group, duplex examination was performed only when physical examination detected an abnormality. The primary end point was the maturation failure rate 8 weeks after fistula creation. Maturation failure was defined as the inability to achieve clinical maturation (i.e., a successful first use) and failure to achieve sonographic maturation (fistula flow >500 ml/min and diameter >6 mm) within 8 weeks. RESULTS: Between June 14, 2012, and June 25, 2014, 150 patients were enrolled (75 patients in each group), and 118 of those were included in the final analysis. The maturation failure rate was lower in the routine duplex group (8 of 59; 13.6%) than in the selective duplex group (15 of 59; 25.4%), but the difference was not statistically significant (odds ratio, 0.46; 95% confidence interval, 0.18 to 1.19; P=0.10). Factors associated with maturation failure were women (odds ratio, 3.84; 95% confidence interval, 1.05 to 14.06; P=0.04), coronary artery disease (odds ratio, 6.36; 95% confidence interval, 1.62 to 24.95; P<0.01), diabetes (odds ratio, 6.10; 95% confidence interval, 1.76 to 21.19; P<0.01), and the preoperative cephalic vein diameter (odds ratio, 0.30; 95% confidence interval, 0.13 to 0.71; P<0.01). CONCLUSIONS: Postoperative routine duplex surveillance failed to prove superiority compared with selective duplex after physical examination for reducing arteriovenous fistula maturation failure. However, the wide 95% confidence interval for the effect of intervention precludes a firm conclusion that routine duplex surveillance was not beneficial. PMID- 27559058 TI - Marine Phytophthora species can hamper conservation and restoration of vegetated coastal ecosystems. AB - Phytophthora species are potent pathogens that can devastate terrestrial plants, causing billions of dollars of damage yearly to agricultural crops and harming fragile ecosystems worldwide. Yet, virtually nothing is known about the distribution and pathogenicity of their marine relatives. This is surprising, as marine plants form vital habitats in coastal zones worldwide (i.e. mangrove forests, salt marshes, seagrass beds), and disease may be an important bottleneck for the conservation and restoration of these rapidly declining ecosystems. We are the first to report on widespread infection of Phytophthora and Halophytophthora species on a common seagrass species, Zostera marina (eelgrass), across the northern Atlantic and Mediterranean. In addition, we tested the effects of Halophytophthora sp. Zostera and Phytophthora gemini on Z. marina seed germination in a full-factorial laboratory experiment under various environmental conditions. Results suggest that Phytophthora species are widespread as we found these oomycetes in eelgrass beds in six countries across the North Atlantic and Mediterranean. Infection by Halophytophthora sp. Zostera, P. gemini, or both, strongly affected sexual reproduction by reducing seed germination sixfold. Our findings have important implications for seagrass ecology, because these putative pathogens probably negatively affect ecosystem functioning, as well as current restoration and conservation efforts. PMID- 27559059 TI - How could fully scaled carps appear in natural waters in Madagascar? AB - The capacity of organisms to rapidly evolve in response to environmental changes is a key feature of evolution, and studying mutation compensation is a way to evaluate whether alternative routes of evolution are possible or not. Common carps (Cyprinus carpio) carrying a homozygous loss-of-function mutation for the scale cover gene fgfr1a1, causing the 'mirror' reduced scale cover, were introduced in Madagascar a century ago. Here we show that carps in Malagasy natural waters are now predominantly covered with scales, though they still all carry the homozygous mutation. We also reveal that the number of scales in mutated carps is under strong polygenic genetic control, with a heritability of 0.49. As a whole, our results suggest that carps submitted to natural selection could evolve a wild-type-like scale cover in less than 40 generations from standing polygenic genetic variation, confirming similar findings mainly retrieved from model organisms. PMID- 27559060 TI - Social connectedness is associated with fibrinogen level in a human social network. AB - Socially isolated individuals face elevated rates of illness and death. Conventional measures of social connectedness reflect an individual's perceived network and can be subject to bias and variation in reporting. In this study of a large human social network, we find that greater indegree, a sociocentric measure of friendship and familial ties identified by a subject's social connections rather than by the subject, predicts significantly lower concentrations of fibrinogen (a biomarker of inflammation and cardiac risk), after adjusting for demographics, education, medical history and known predictors of cardiac risk. The association between fibrinogen and social isolation, as measured by low indegree, is comparable to the effect of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual's perceived connectedness, displays a significantly weaker association with fibrinogen concentrations. PMID- 27559061 TI - Global mammal beta diversity shows parallel assemblage structure in similar but isolated environments. AB - The taxonomic, phylogenetic and trait dimensions of beta diversity each provide us unique insights into the importance of historical isolation and environmental conditions in shaping global diversity. These three dimensions should, in general, be positively correlated. However, if similar environmental conditions filter species with similar trait values, then assemblages located in similar environmental conditions, but separated by large dispersal barriers, may show high taxonomic, high phylogenetic, but low trait beta diversity. Conversely, we expect lower phylogenetic diversity, but higher trait biodiversity among assemblages that are connected but are in differing environmental conditions. We calculated all pairwise comparisons of approximately 110 * 110 km grid cells across the globe for more than 5000 mammal species (approx. 70 million comparisons). We considered realms as units representing geographical distance and historical isolation and biomes as units with similar environmental conditions. While beta diversity dimensions were generally correlated, we highlight geographical regions of decoupling among beta diversity dimensions. Our analysis shows that assemblages from tropical forests in different realms had low trait dissimilarity while phylogenetic beta diversity was significantly higher than expected, suggesting potential convergent evolution. Low trait beta diversity was surprisingly not found between isolated deserts, despite harsh environmental conditions. Overall, our results provide evidence for parallel assemblage structure of mammal assemblages driven by environmental conditions at a global scale. PMID- 27559062 TI - Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus. AB - Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization. PMID- 27559064 TI - Soil management shapes ecosystem service provision and trade-offs in agricultural landscapes. AB - Agroecosystems are principally managed to maximize food provisioning even if they receive a large array of supporting and regulating ecosystem services (ESs). Hence, comprehensive studies investigating the effects of local management and landscape composition on the provision of and trade-offs between multiple ESs are urgently needed. We explored the effects of conservation tillage, nitrogen fertilization and landscape composition on six ESs (crop production, disease control, soil fertility, water quality regulation, weed and pest control) in winter cereals. Conservation tillage enhanced soil fertility and pest control, decreased water quality regulation and weed control, without affecting crop production and disease control. Fertilization only influenced crop production by increasing grain yield. Landscape intensification reduced the provision of disease and pest control. We also found tillage and landscape composition to interactively affect water quality regulation and weed control. Under N fertilization, conventional tillage resulted in more trade-offs between ESs than conservation tillage. Our results demonstrate that soil management and landscape composition affect the provision of several ESs and that soil management potentially shapes the trade-offs between them. PMID- 27559063 TI - Number sense and state-dependent valuation in cuttlefish. AB - Identifying the amount of prey available is an important part of an animal's foraging behaviour. The risk-sensitive foraging theory predicts that an organism's foraging decisions with regard to food rewards depending upon its satiation level. However, the precise interaction between optimal risk-tolerance and satiation level remains unclear. In this study, we examined, firstly, whether cuttlefish, with one of the most highly evolved nervous system among the invertebrates, have number sense, and secondly, whether their valuation of food reward is satiation state dependent. When food such as live shrimps is present, without training, cuttlefish turn toward the prey and initiate seizure behaviour. Using this visual attack behaviour as a measure, cuttlefish showed a preference for a larger quantity when faced with two-alternative forced choice tasks (1 versus 2, 2 versus 3, 3 versus 4 and 4 versus 5). However, cuttlefish preferred the small quantity when the choice was between one live and two dead shrimps. More importantly, when the choice was between one large live shrimp and two small live shrimps (a prey size and quantity trade-off), the cuttlefish chose the large single shrimp when they felt hunger, but chose the two smaller prey when they were satiated. These results demonstrate that cuttlefish are capable of number discrimination and that their choice of prey number depends on the quality of the prey and on their appetite state. The findings also suggest that cuttlefish integrate both internal and external information when making a foraging decision and that the cost of obtaining food is inversely correlated with their satiation level, a phenomenon similar to the observation that metabolic state alters economic decision making under risk among humans. PMID- 27559065 TI - Correction to 'Metabolomics of reef benthic interactions reveals a bioactive lipid involved in coral defence'. PMID- 27559066 TI - Sea urchins in a high-CO2 world: the influence of acclimation on the immune response to ocean warming and acidification. AB - Climate-induced ocean warming and acidification may render marine organisms more vulnerable to infectious diseases. We investigated the effects of warming and acidification on the immune response of the sea urchin Heliocidaris erythrogramma Sea urchins were gradually introduced to four combinations of temperature and pHNIST (17 degrees C/pH 8.15, 17 degrees C/pH 7.6, 23 degrees C/pH 8.15 and 23 degrees C/pH 7.6) and then held in temperature-pH treatments for 1, 15 or 30 days to determine if the immune response would adjust to stressors over time. Coelomocyte concentration and type, phagocytic capacity and bactericidal activity were measured on day 1, 15 and 30 with different sea urchins used each time. At each time point, the coelomic fluid of individuals exposed to increased temperature and acidification had the lowest coelomocyte concentrations, exhibited lower phagocytic capacities and was least effective at inhibiting bacterial growth of the pathogen Vibrio anguillarum Over time, increased temperature alleviated the negative effects of acidification on phagocytic activity. Our results demonstrate the importance of incorporating acclimation time to multiple stressors when assessing potential responses to future ocean conditions and indicate that the immune response of H. erythrogramma may be compromised under near-future ocean warming and acidification. PMID- 27559067 TI - Sperm morphology, adenosine triphosphate (ATP) concentration and swimming velocity: unexpected relationships in a passerine bird. AB - The relationship between sperm energetics and sperm function is poorly known, but is central to our understanding of the evolution of sperm traits. The aim of this study was to examine how sperm morphology and ATP content affect sperm swimming velocity in the zebra finch Taeniopygia guttata We exploited the high inter-male variation in this species and created extra experimental power by increasing the number of individuals with very long or short sperm through artificial selection. We found a pronounced quadratic relationship between total sperm length and swimming velocity, with velocity increasing with length up to a point, but declining in the very longest sperm. We also found an unexpected negative association between midpiece length and ATP content: sperm with a short midpiece generally contained the highest concentration of ATP. Low intracellular ATP is therefore unlikely to explain reduced swimming velocity among the very longest sperm (which tend to have a shorter midpiece). PMID- 27559068 TI - Correction to 'Controlled comparison of species- and community-level models across novel climates and communities'. PMID- 27559069 TI - Correction to 'Elevated germline mutation rate in teenage fathers'. PMID- 27559070 TI - Correction to 'Bypass of genetic constraints during mutator evolution to antibiotic resistance'. PMID- 27559071 TI - Late-Onset Asthma Predicts Cardiovascular Disease Events: The Wisconsin Sleep Cohort. AB - BACKGROUND: Asthma is a heterogeneous syndrome with different clinical subtypes that is associated with an increased risk for cardiovascular disease (CVD). We hypothesized that the late-onset subtype of asthma is associated with a higher risk of incident CVD. METHODS AND RESULTS: Participants from the Wisconsin Sleep Cohort free of CVD at baseline were followed for a mean (SD) of 13.9 (5.9) years for development of CVD (myocardial infarction, angina, stroke, coronary revascularization, heart failure, or CVD death). Late-onset asthma was defined as physician-diagnosed asthma at age >=18 years. Multivariable Cox regression models adjusted for age, sex, and CVD risk factors were used to assess associations of late-onset asthma and incident CVD. The 1269 participants were 47.3 (8.0) years old; 166 participants had asthma (111 late-onset, 55 early-onset). Participants with late-onset asthma compared to nonasthmatics were more likely to be female (67% versus 44%) and to have a higher body-mass index (32.2 versus 29.4 kg/m(2)) (P<0.05). Mean age of asthma diagnosis in the late-onset group was 39.5 (9.6) years versus 8.9 (5.7) years in the early-onset group (P<0.0001). Late-onset asthmatics had a higher adjusted risk of incident CVD than nonasthmatics (hazard ratio 1.57, 95% CI 1.01-2.45, P=0.045). There was no interaction between body mass index and age of asthma diagnosis on incident CVD (P=0.83). CONCLUSIONS: In a large cohort study of adults followed prospectively for over a decade, late onset asthmatics had an increased risk of incident CVD events that persisted after adjustment for age, sex, and CVD risk factors. PMID- 27559072 TI - Sex Differences in Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Heart Disease. AB - BACKGROUND: Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress-induced myocardial ischemia (MSIMI). METHODS AND RESULTS: We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent (99m)Tc sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women <=50 years was almost 4-fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress. CONCLUSIONS: Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group. PMID- 27559073 TI - Mental Stress and Myocardial Ischemia: Young Women at Risk. PMID- 27559076 TI - Severely Schizophrenic and Successful? Yes, it's Possible! PMID- 27559074 TI - Navigating Microbiological Food Safety in the Era of Whole-Genome Sequencing. AB - The epidemiological investigation of a foodborne outbreak, including identification of related cases, source attribution, and development of intervention strategies, relies heavily on the ability to subtype the etiological agent at a high enough resolution to differentiate related from nonrelated cases. Historically, several different molecular subtyping methods have been used for this purpose; however, emerging techniques, such as single nucleotide polymorphism (SNP)-based techniques, that use whole-genome sequencing (WGS) offer a resolution that was previously not possible. With WGS, unlike traditional subtyping methods that lack complete information, data can be used to elucidate phylogenetic relationships and disease-causing lineages can be tracked and monitored over time. The subtyping resolution and evolutionary context provided by WGS data allow investigators to connect related illnesses that would be missed by traditional techniques. The added advantage of data generated by WGS is that these data can also be used for secondary analyses, such as virulence gene detection, antibiotic resistance gene profiling, synteny comparisons, mobile genetic element identification, and geographic attribution. In addition, several software packages are now available to generate in silico results for traditional molecular subtyping methods from the whole-genome sequence, allowing for efficient comparison with historical databases. Metagenomic approaches using next generation sequencing have also been successful in the detection of nonculturable foodborne pathogens. This review addresses state-of-the-art techniques in microbial WGS and analysis and then discusses how this technology can be used to help support food safety investigations. Retrospective outbreak investigations using WGS are presented to provide organism-specific examples of the benefits, and challenges, associated with WGS in comparison to traditional molecular subtyping techniques. PMID- 27559078 TI - Adapting Experiential Learning to Develop Problem-Solving Skills in Deaf and Hard of-Hearing Engineering Students. AB - Individuals who are deaf and hard-of-hearing (DHH) are underrepresented in science, technology, engineering, and mathematics (STEM) professions, and this may be due in part to their level of preparation in the development and retention of mathematical and problem-solving skills. An approach was developed that incorporates experiential learning and best practices of STEM instruction to give first-year DHH students enrolled in a postsecondary STEM program the opportunity to develop problem-solving skills in real-world scenarios. Using an industrial engineering laboratory that provides manufacturing and warehousing environments, students were immersed in real-world scenarios in which they worked on teams to address prescribed problems encountered during the activities. The highly structured, Plan-Do-Check-Act approach commonly used in industry was adapted for the DHH student participants to document and communicate the problem-solving steps. Students who experienced the intervention realized a 14.6% improvement in problem-solving proficiency compared with a control group, and this gain was retained at 6 and 12 months, post-intervention. PMID- 27559079 TI - Heartbeat: Cardiac rehabilitation in low-resource settings. PMID- 27559077 TI - Temporal Lobe Volume Decrements in Psychosis Spectrum Youths. AB - Structural brain abnormalities have been amply demonstrated in schizophrenia. These include volume decrements in the perirhinal/entorhinal regions of the ventromedial temporal lobe, which comprise the primary olfactory cortex. Olfactory impairments, which are a hallmark of schizophrenia, precede the onset of illness, distinguish adolescents experiencing prodromal symptoms from healthy youths, and may predict the transition from the prodrome to frank psychosis. We therefore examined temporal lobe regional volumes in a large adolescent sample to determine if structural deficits in ventromedial temporal lobe areas were associated, not only with schizophrenia, but also with a heightened risk for psychosis. Seven temporal lobe regional volumes (amygdala [AM], hippocampus, inferior temporal gyrus, parahippocampal gyrus, superior temporal gyrus, temporal pole, and entorhinal cortex [EC]) were measured in 386 psychosis spectrum adolescents, 521 adolescents with other types of psychopathology, and 359 healthy adolescents from the Philadelphia Neurodevelopment Cohort. Total intracranial and left EC volumes, which were both smallest among the psychosis spectrum, were the only measures that distinguished all 3 groups. Left AM was also smaller in psychosis spectrum compared with healthy subjects. EC volume decrement was strongly correlated with impaired cognition and less robustly associated with heightened negative/disorganized symptoms. AM volume decrement correlated with positive symptoms (persecution/special abilities). Temporal lobe volumes classified psychosis spectrum youths with very high specificity but relatively low sensitivity. These MRI measures may therefore serve as important confirmatory biomarkers denoting a worrisome preclinical trajectory among at-risk youths, and the specific pattern of deficits may predict specific symptom profiles. PMID- 27559075 TI - Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications. AB - HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis. PMID- 27559080 TI - Young investigators at the British Cardiovascular Society Annual Conference in June 2016. PMID- 27559082 TI - Coherent control of long-range photoinduced electron transfer by stimulated X-ray Raman processes. AB - We show that X-ray pulses resonant with selected core transitions can manipulate electron transfer (ET) in molecules with ultrafast and atomic selectivity. We present possible protocols for coherently controlling ET dynamics in donor-bridge acceptor (DBA) systems by stimulated X-ray resonant Raman processes involving various transitions between the D, B, and A sites. Simulations presented for a Ru(II)-Co(III) model complex demonstrate how the shapes, phases and amplitudes of the X-ray pulses can be optimized to create charge on demand at selected atoms, by opening up otherwise blocked ET pathways. PMID- 27559081 TI - Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs. AB - There is growing recognition that small open reading frames (sORFs) encoding peptides shorter than 100 amino acids are an important class of functional elements in the eukaryotic genome, with several already identified to play critical roles in growth, development, and disease. However, our understanding of their biological importance has been hindered owing to the significant technical challenges limiting their annotation. Here we combined ultra-deep sequencing of ribosome-associated poly-adenylated RNAs with rigorous conservation analysis to identify a comprehensive population of translated sORFs during early Drosophila embryogenesis. In total, we identify 399 sORFs, including those previously annotated but without evidence of translational capacity, those found within transcripts previously classified as non-coding, and those not previously known to be transcribed. Further, we find, for the first time, evidence for translation of many sORFs with different isoforms, suggesting their regulation is as complex as longer ORFs. Furthermore, many sORFs are found not associated with ribosomes in late-stage Drosophila S2 cells, suggesting that many of the translated sORFs may have stage-specific functions during embryogenesis. These results thus provide the first comprehensive annotation of the sORFs present during early Drosophila embryogenesis, a necessary basis for a detailed delineation of their function in embryogenesis and other biological processes. PMID- 27559083 TI - Electron anions and the glass transition temperature. AB - Properties of glasses are typically controlled by judicious selection of the glass-forming and glass-modifying constituents. Through an experimental and computational study of the crystalline, molten, and amorphous [Ca12Al14O32](2+) ? (e(-))2, we demonstrate that electron anions in this system behave as glass modifiers that strongly affect solidification dynamics, the glass transition temperature, and spectroscopic properties of the resultant amorphous material. The concentration of such electron anions is a consequential control parameter: It invokes materials evolution pathways and properties not available in conventional glasses, which opens a unique avenue in rational materials design. PMID- 27559084 TI - Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer. AB - Targeting glutamine metabolism via pharmacological inhibition of glutaminase has been translated into clinical trials as a novel cancer therapy, but available drugs lack optimal safety and efficacy. In this study, we used a proprietary emulsification process to encapsulate bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2 yl)ethyl sulfide (BPTES), a selective but relatively insoluble glutaminase inhibitor, in nanoparticles. BPTES nanoparticles demonstrated improved pharmacokinetics and efficacy compared with unencapsulated BPTES. In addition, BPTES nanoparticles had no effect on the plasma levels of liver enzymes in contrast to CB-839, a glutaminase inhibitor that is currently in clinical trials. In a mouse model using orthotopic transplantation of patient-derived pancreatic tumor tissue, BPTES nanoparticle monotherapy led to modest antitumor effects. Using the HypoxCR reporter in vivo, we found that glutaminase inhibition reduced tumor growth by specifically targeting proliferating cancer cells but did not affect hypoxic, noncycling cells. Metabolomics analyses revealed that surviving tumor cells following glutaminase inhibition were reliant on glycolysis and glycogen synthesis. Based on these findings, metformin was selected for combination therapy with BPTES nanoparticles, which resulted in significantly greater pancreatic tumor reduction than either treatment alone. Thus, targeting of multiple metabolic pathways, including effective inhibition of glutaminase by nanoparticle drug delivery, holds promise as a novel therapy for pancreatic cancer. PMID- 27559085 TI - Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. AB - Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patients presented with neonatal-onset fever, neutrophilic dermatitis/panniculitis, and failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected with mutated OTULIN had decreased enzyme activity relative to cells transfected with WT OTULIN, and showed a substantial defect in the linear deubiquitination of target molecules. Stimulated patients' fibroblasts and peripheral blood mononuclear cells showed evidence for increased signaling in the canonical NF-kappaB pathway and accumulated linear ubiquitin aggregates. Levels of proinflammatory cytokines were significantly increased in the supernatants of stimulated primary cells and serum samples. This discovery adds to the emerging spectrum of human diseases caused by defects in the ubiquitin pathway and suggests a role for targeted cytokine therapies. PMID- 27559086 TI - Impact of membrane lipid composition on the structure and stability of the transmembrane domain of amyloid precursor protein. AB - Cleavage of the amyloid precursor protein (APP) by gamma-secretase is a crucial first step in the evolution of Alzheimer's disease. To discover the cleavage mechanism, it is urgent to predict the structures of APP monomers and dimers in varying membrane environments. We determined the structures of the C9923-55 monomer and homodimer as a function of membrane lipid composition using a multiscale simulation approach that blends atomistic and coarse-grained models. We demonstrate that the C9923-55 homodimer structures form a heterogeneous ensemble with multiple conformational states, each stabilized by characteristic interpeptide interactions. The relative probabilities of each conformational state are sensitive to the membrane environment, leading to substantial variation in homodimer peptide structure as a function of membrane lipid composition or the presence of an anionic lipid environment. In contrast, the helicity of the transmembrane domain of monomeric C991-55 is relatively insensitive to the membrane lipid composition, in agreement with experimental observations. The dimer structures of human EphA2 receptor depend on the lipid environment, which we show is linked to the location of the structural motifs in the dimer interface, thereby establishing that both sequence and membrane composition modulate the complete energy landscape of membrane-bound proteins. As a by product of our work, we explain the discrepancy in structures predicted for C99 congener homodimers in membrane and micelle environments. Our study provides insight into the observed dependence of C99 protein cleavage by gamma-secretase, critical to the formation of amyloid-beta protein, on membrane thickness and lipid composition. PMID- 27559087 TI - Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes. AB - The strongest genetic risk factor influencing susceptibility to late-onset Alzheimer's disease (AD) is apolipoprotein E (APOE) genotype. APOE has three common isoforms in humans, E2, E3, and E4. The presence of two copies of the E4 allele increases risk by ~12-fold whereas E2 allele is associated with an ~twofold decreased risk for AD. These data put APOE central to AD pathophysiology, but it is not yet clear how APOE alleles modify AD risk. Recently we found that astrocytes, a major central nervous system cell type that produces APOE, are highly phagocytic and participate in normal synapse pruning and turnover. Here, we report a novel role for APOE in controlling the phagocytic capacity of astrocytes that is highly dependent on APOE isoform. APOE2 enhances the rate of phagocytosis of synapses by astrocytes, whereas APO4 decreases it. We also found that the amount of C1q protein accumulation in hippocampus, which may represent the accumulation of senescent synapses with enhanced vulnerability to complement-mediated degeneration, is highly dependent on APOE alleles: C1q accumulation was significantly reduced in APOE2 knock-in (KI) animals and was significantly increased in APOE4 KI animals compared with APOE3 KI animals. These studies reveal a novel allele-dependent role for APOE in regulating the rate of synapse pruning by astrocytes. They also suggest the hypothesis that AD susceptibility of APOE4 may originate in part from defective phagocytic capacity of astrocytes which accelerates the rate of accumulation of C1q-coated senescent synapses, enhancing synaptic vulnerability to classical-complement-cascade mediated neurodegeneration. PMID- 27559089 TI - Wettability control on multiphase flow in patterned microfluidics. AB - Multiphase flow in porous media is important in many natural and industrial processes, including geologic CO2 sequestration, enhanced oil recovery, and water infiltration into soil. Although it is well known that the wetting properties of porous media can vary drastically depending on the type of media and pore fluids, the effect of wettability on multiphase flow continues to challenge our microscopic and macroscopic descriptions. Here, we study the impact of wettability on viscously unfavorable fluid-fluid displacement in disordered media by means of high-resolution imaging in microfluidic flow cells patterned with vertical posts. By systematically varying the wettability of the flow cell over a wide range of contact angles, we find that increasing the substrate's affinity to the invading fluid results in more efficient displacement of the defending fluid up to a critical wetting transition, beyond which the trend is reversed. We identify the pore-scale mechanisms-cooperative pore filling (increasing displacement efficiency) and corner flow (decreasing displacement efficiency) responsible for this macroscale behavior, and show that they rely on the inherent 3D nature of interfacial flows, even in quasi-2D media. Our results demonstrate the powerful control of wettability on multiphase flow in porous media, and show that the markedly different invasion protocols that emerge-from pore filling to postbridging-are determined by physical mechanisms that are missing from current pore-scale and continuum-scale descriptions. PMID- 27559090 TI - Diet-heart disease hypothesis is unaffected by results of analysis of recovered data from Minnesota Coronary Experiment. PMID- 27559088 TI - Rab5 and its effector FHF contribute to neuronal polarity through dynein dependent retrieval of somatodendritic proteins from the axon. AB - An open question in cell biology is how the general intracellular transport machinery is adapted to perform specialized functions in polarized cells such as neurons. Here we illustrate this adaptation by elucidating a role for the ubiquitous small GTPase Ras-related protein in brain 5 (Rab5) in neuronal polarity. We show that inactivation or depletion of Rab5 in rat hippocampal neurons abrogates the somatodendritic polarity of the transferrin receptor and several glutamate receptor types, resulting in their appearance in the axon. This loss of polarity is not caused primarily by increased transport from the soma to the axon but rather by decreased retrieval from the axon to the soma. Retrieval is also dependent on the Rab5 effector Fused Toes (FTS)-Hook-FTS and Hook interacting protein (FHIP) (FHF) complex, which interacts with the minus-end directed microtubule motor dynein and its activator dynactin to drive a population of axonal retrograde carriers containing somatodendritic proteins toward the soma. These findings emphasize the importance of both biosynthetic sorting and axonal retrieval for the polarized distribution of somatodendritic receptors at steady state. PMID- 27559091 TI - Influence of cytokine gene polymorphisms on proinflammatory/anti-inflammatory cytokine imbalance in premature coronary artery disease. AB - BACKGROUND: Genetic information has the potential to create a more personalised, prompt, early and accurate risk evaluation. The effect of these genetic variants on the serum biomarker levels (phenotype) needs to be studied to assess their potential causal role in the pathogenesis of premature coronary artery disease (PCAD). Objectives were to determine the genotypic distribution of interleukin (IL) 18, tumour necrosis factor-alpha (TNFA), IL6 and IL10 single nucleotide polymorphisms (SNPs) in Pakistani PCAD cases and disease free controls and to study the effect of these gene polymorphisms on the serum cytokine levels (IL18, TNFA, IL6 and IL10) and cytokine imbalance (IL18:IL10 and TNFA:IL10). MATERIAL AND METHODS: The case-control study was carried out in National University of Sciences and Technology, Islamabad in collaboration with the Cardiovascular Genetics Institute, University College London, UK. Subjects (n=340) with >70% stenosis in at least a single major coronary artery on angiography were taken as PCAD cases along with 310 angiographically verified controls. ELISA was performed for measuring the concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using TAQMAN assay. RESULTS: The risk allele frequencies (RAFs) of rs1800795 (IL6) and rs187238 (IL18) cytokine gene promoter SNPs were significantly higher in the PCAD cases as compared with the controls. Serum IL18 and IL10 levels were significantly greater in the IL18 rs187238 GG genotype patients while serum IL18 and IL6 levels were significantly higher in patients having the IL6 rs1800795 CC genotype. IL18 SNP rs1946519 significantly altered the IL18, TNFA, IL6, IL18/IL10 and TNFA/IL10 ratio levels followed by TNFA SNP rs1800629 which significantly altered the serum levels of IL18, IL18:IL-0 and TNFA:IL10 ratios. CONCLUSIONS: The association of the selected SNPs with differential serum cytokine levels especially the cytokine imbalance points towards their potential causal role in the immune inflammatory pathogenic pathway of PCAD. PMID- 27559092 TI - New perspectives on atrial fibrillation and stroke. AB - Atrial fibrillation (AF) is directly implicated in embolic stroke and suspected in a large proportion of cryptogenic stroke. The current stroke-prevention strategy in embolic and cryptogenic stroke starts with arrhythmia detection, followed by risk stratification and treatment for those deemed to be at increased risk. This approach is practical and widespread; however, more recent findings have questioned its validity. Arrhythmia detection is dependent on the length and fidelity of monitoring. Long-term monitoring using implanted recorders improves arrhythmia detection in patients with cryptogenic stroke. A large proportion of patients with cryptogenic stroke, however, were shown not to have any AF. Moreover, in patients with permanent pacemakers who also experienced thromboembolic events, AF did not always precede thromboembolisation. These results raise cause and effect questions about the role of AF, the arrhythmia, in thrombus formation and embolisation. Moreover, risk estimation scores; such as Congestive heart failure, Hypertension, Age, Diabetes and previous Stroke or Transient Ischaemic Attack, Vascular disease and female sex category (CHA2DS2 VASc), have a suboptimal predictive accuracy and the mechanism relating their individual components to thrombogenesis is unknown. Given these limitations, a more comprehensive and mechanistic evaluation of atrial disease is needed to better identify patients at risk for stroke and AF. Atrial fibrosis, quantified using late gadolinium enhancement cardiac MRI, is associated with reduced atrial function, stroke and the presence of left atrial thrombus in patients with AF. Biomarkers such as B-type natriuretic peptide, cardiac troponin have also been linked to increased thromboembolic risk and AF. PMID- 27559093 TI - Cardiovascular magnetic resonance imaging: what the general cardiologist should know. PMID- 27559095 TI - Factor XIa-specific IgG and a reversal agent to probe factor XI function in thrombosis and hemostasis. AB - Thrombosis is a major cause of morbidity and mortality. Current antithrombotic drugs are not ideal in that they must balance prevention of thrombosis against bleeding risk. Inhibition of coagulation factor XI (FXI) may offer an improvement over existing antithrombotic strategies by preventing some forms of thrombosis with lower bleeding risk. To permit exploration of this hypothesis in humans, we generated and characterized a series of human immunoglobulin Gs (IgGs) that blocked FXIa active-site function but did not bind FXI zymogen or other coagulation proteases. The most potent of these IgGs, C24 and DEF, inhibited clotting in whole human blood and prevented FeCl3-induced carotid artery occlusion in FXI-deficient mice reconstituted with human FXI and in thread induced venous thrombosis in rabbits at clinically relevant doses. At doses substantially higher than those required for inhibition of intravascular thrombus formation in these models, DEF did not increase cuticle bleeding in rabbits or cause spontaneous bleeding in macaques over a 2-week study. Anticipating the desirability of a reversal agent, we also generated a human IgG that rapidly reversed DEF activity ex vivo in human plasma and in vivo in rabbits. Thus, an active site-directed FXIa-specific antibody can block thrombosis in animal models and, together with the reversal agent, may facilitate exploration of the roles of FXIa in human disease. PMID- 27559094 TI - Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. AB - Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naive CD4(+) T cell differentiation into TH1 and TH17 by down regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation. PMID- 27559097 TI - Comment on "Absence of sperm RNA elements correlates with idiopathic male infertility". AB - The spermatozoal population used for a recent RNA sequencing study may have been contaminated by somatic cell types because of an inefficient sperm purification procedure. PMID- 27559098 TI - Response to Comment on "Absence of sperm RNA elements correlates with idiopathic male infertility". AB - RNAs from other cell types have minimal impact on male fecundity-associated sperm RNA elements. PMID- 27559096 TI - Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma. AB - Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin alphaVbeta3/alpha5beta1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. PMID- 27559099 TI - Perspectives on current child health issues. PMID- 27559100 TI - Social media: the relevance for research. PMID- 27559104 TI - Editorial. PMID- 27559105 TI - Is epilepsy a curable neurodegenerative disease? PMID- 27559106 TI - Serotonergic loss underlying apathy in Parkinson's disease. PMID- 27559107 TI - Distinct pathways for cognitive decline in the presence of Alzheimer's disease pathology or cerebrovascular disease. PMID- 27559108 TI - Amyloid imaging and Alzheimer's disease: the unsolved cases. PMID- 27559111 TI - Modeling mesothelioma utilizing human mesothelial cells reveals involvement of phospholipase-C beta 4 in YAP-active mesothelioma cell proliferation. AB - Mesotheliomas are frequently characterized by disruption of Hippo pathway due to deletion and/or mutation in genes, such as neurofibromin 2 (NF2). Hippo disruption attenuates yes-associated protein (YAP) phosphorylation allowing YAP to translocate to the nucleus and regulate gene expression. The role of disrupted Hippo pathway in maintenance of established mesotheliomas has been extensively investigated using cell lines; however, its involvement in development of human mesothelioma has not been explored much. Here, we employed immortalized human mesothelial cells to disrupt Hippo pathway. YAP phosphorylation was reduced on NF2 knockdown and the cells exhibited altered growth in vitro, developing tumors when transplanted into nude mice. Similar results were obtained from enforced expression of wild-type or constitutively active (S127A) YAP, indicating the crucial role of activated YAP in the transformation of mesothelial cells. Gene expression analysis comparing control- and YAP-transduced immortalized human mesothelial cells revealed phospholipase-C beta 4 (PLCB4) to be among the genes highly upregulated by YAP. PLCB4 was upregulated by YAP in immortalized human mesothelial cells and downregulated on YAP knockdown in Hippo-disrupted mesothelioma cell lines. PLCB4 knockdown attenuated the growth of YAP-transduced immortalized mesothelial cells and YAP-active, but not YAP-nonactive, mesothelioma cell lines. Our model system thus provides a versatile tool to investigate the mechanisms underlying mesothelioma development. We suggest that PLCB4 may be an attractive drug target for the treatment of mesothelioma. PMID- 27559110 TI - Collapsed methylation quantitative trait loci analysis for low frequency and rare variants. AB - BACKGROUND: Single variant approaches have been successful in identifying DNA methylation quantitative trait loci (mQTL), although as with complex traits they lack the statistical power to identify the effects from rare genetic variants. We have undertaken extensive analyses to identify regions of low frequency and rare variants that are associated with DNA methylation levels. METHODS: We used repeated measurements of DNA methylation from five different life stages in human blood, taken from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Variants were collapsed across CpG islands and their flanking regions to identify variants collectively associated with methylation, where no single variant was individually responsible for the observed signal. All analyses were undertaken using the sequence kernel association test. RESULTS: For loci where no individual variant mQTL was observed based on a single variant analysis, we identified 95 unique regions where the combined effect of low frequency variants (MAF <= 5%) provided strong evidence of association with methylation. For loci where there was previous evidence of an individual variant mQTL, a further 3 regions provided evidence of association between multiple low frequency variants and methylation levels. Effects were observed consistently across 5 different time points in the lifecourse and evidence of replication in the TwinsUK and Exeter cohorts was also identified. CONCLUSION: We have demonstrated the potential of this novel approach to mQTL analysis by analysing the combined effect of multiple low frequency or rare variants. Future studies should benefit from applying this approach as a complementary follow up to single variant analyses. PMID- 27559113 TI - Osteoarthritis. PMID- 27559112 TI - Silencing of ST6Gal I enhances colorectal cancer metastasis by down-regulating KAI1 via exosome-mediated exportation and thereby rescues integrin signaling. AB - Aberrant sialylation has long been correlated with human cancer. Increased ST6 Gal I (beta-galactoside alpha 2, 6 sialyltransferase) and consequently higher levels of cell-surface alpha 2, 6 sialylation has been associated with human colorectal cancer (CRC) metastasis. We have extensive circumstantial data that sialylation is connected to cancer metastasis, but we do not understand in detail how sialylation can switch on/off multiple steps in cancer metastasis. To investigate the molecular mechanism underlying the ST6Gal I-mediated metastasis of CRC, we silenced the ST6Gal I gene in a metastatic SW620 CRC cell line (SW620 shST6Gal I) and examined the metastatic behavior of the cells. We found that various hallmarks of metastatic ability were considerably enhanced in ST6Gal 1 depleted SW620 clones, as assessed both in vitro and in vivo In particular, the metastasis suppressor, KAI1, was down-regulated in ST6Gal I-deficient SW620 clones. This reflected the increased exosome-mediated exportation of KAI1, and was associated with a decrease in the KAI1-mediated inhibition of integrin. These findings indicate that gene silencing of ST6Gal I could enhance metastasis of CRC by down-regulating KAI1 activity and rescuing its negative effects on integrin signaling. PMID- 27559109 TI - A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways. AB - More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data. The meta-analysis (N = 5758) followed by replication (N = 3784) identified a genome-wide significant association between rs8111874 and diarrhoea at age 1 year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, and the immune and neuro-secretory systems were detected as relevant organs. In summary, this genome-wide association meta analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population. PMID- 27559114 TI - Navigating the medical humanities: my route. PMID- 27559116 TI - It's Just Old Age. PMID- 27559115 TI - Scholar spotlight on Dr Charlotte Blease and Prof Allan Peterkin. PMID- 27559117 TI - Detection of the plasmid-mediated colistin-resistance gene mcr-1 in faecal metagenomes of Dutch travellers. AB - BACKGROUND: Recently, the first plasmid-mediated colistin-resistance gene, mcr-1, was reported. Colistin is increasingly used as an antibiotic of last resort for the treatment of infections caused by carbapenem-resistant bacteria, which have been rapidly disseminating worldwide in recent years. OBJECTIVES: The reported carriage rate of mcr-1 in humans remains sporadic thus far, except for those reported in Chinese populations. We aimed to determine its presence in the faecal metagenomes of healthy Dutch travellers between 2010 and 2012. METHODS: Faecal metagenomic DNA of pre- and post-travel samples from 122 healthy Dutch long distance travellers was screened for the presence of mcr-1 using a TaqMan quantitative PCR assay, which was designed in this study. All positive samples were confirmed by sequencing of the amplicons. RESULTS: The mcr-1 gene was detected in 6 (4.9%, 95% CI = 2.1%-10.5%) of 122 healthy Dutch long-distance travellers after they had visited destinations in South(-east) Asia or southern Africa between 2011 and 2012. One of these participants was already found to be positive before travel. CONCLUSIONS: Our study highlights the potential of PCR based targeted metagenomics as an unbiased and sensitive method to screen for the carriage of the mcr-1 gene and suggests that mcr-1 is widespread in various parts of the world. The observation that one participant was found to be positive before travel suggests that mcr-1 may already have disseminated to the microbiomes of Dutch residents at a low prevalence, warranting a more extensive investigation of its prevalence in the general population and possible sources. PMID- 27559118 TI - Results from the Survey of Antibiotic Resistance (SOAR) 2012-14 in Thailand, India, South Korea and Singapore. PMID- 27559119 TI - Evaluation of the Scan(r) 1200 as a rapid tool for reading antibiotic susceptibility testing by the disc diffusion technique. AB - OBJECTIVES: In clinical microbiology, some instruments are able to automatically read inhibition zone diameters for antibiotic susceptibility testing (AST) performed by the disc diffusion (DD) method. The actual resolution of commercial reader systems is low and high-resolution scanners have been developed for microbiology. Here, we evaluated and compared the reading and interpretation of AST by the DD method using the Scan(r) 1200 instrument as compared with the Sirscan(r) system on 211 clinical strains and the possibility to read AST after 6 or 8 h of incubation as compared with 24 h on 121 additional Gram-negative strains and 76 non-fermenter Gram-negative and Gram-positive strains. METHODS: Validation of the technique was assessed on three reference strains as requested by EUCAST for analysis of the repeatability and reproducibility of the method. RESULTS: Correlation between the two methods, assessed using 211 clinical isolates (n = 2439 zones of growth inhibition measured), was excellent with a correlation coefficient of 0.97. For the earlier reading experiments, preliminary results demonstrate the possibility of reading AST for drug-species combinations after 6 and 8 h for Gram-negative bacteria with rapid growth (correlation coefficient at 6 h = 0.96 and at 8 h = 0.98) and at 8 or 10 h for Gram-positive bacteria. CONCLUSIONS: The Scan(r) 1200 has many advantages thanks to its small size, rapidity of use and high-resolution imaging allowing the possibility to improve AST results after only 6-8 h of incubation. This AST reader system represents a robust alternative tool for routine use in clinical microbiology laboratories. PMID- 27559120 TI - Comparative in vitro activities of ceftaroline and ceftriaxone against bacterial pathogens associated with respiratory tract infections: results from the AWARE surveillance study. AB - OBJECTIVES: Ceftaroline fosamil is indicated for the treatment of community acquired bacterial pneumonia and ceftriaxone has an indication for lower respiratory tract infections. This study was conducted to compare the relative in vitro activities of these two agents against bacterial species associated with community-associated respiratory tract infections. METHODS: In all, 13 005 isolates of Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected in 2012-14 from 39 countries in the Asia-Pacific region, Europe, Latin America and Africa-Middle East from respiratory tract specimens. The identification was confirmed centrally by MALDI-TOF and broth microdilution susceptibility testing and interpretation was done according to CLSI guidelines. RESULTS: Ceftaroline was 16-fold more potent against MSSA (MIC90 0.25 versus 4 mg/L) than ceftriaxone and >=16-fold more potent against MRSA (MIC90 2 versus >32 mg/L). Ceftaroline was 16-fold more potent against S. pneumoniae (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1-2 mg/L), with higher MIC values observed among penicillin-non susceptible isolates for both agents. Similar activity (MIC90 <=0.03 mg/L) was observed for ceftaroline and ceftriaxone against H. influenzae, with higher MIC values observed in the Asia-Pacific region for both agents compared with other regions. Ceftaroline was 4- to 8-fold more active against M. catarrhalis (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1 mg/L). CONCLUSIONS: These global MIC data demonstrated that ceftaroline exhibited superior in vitro activity compared with ceftriaxone against bacterial species that commonly cause community-associated respiratory tract infections. PMID- 27559121 TI - Opportunistic Diseases During HIV Infection-Things Aren't What They Used to Be, or Are They? PMID- 27559125 TI - Erratum: Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy. PMID- 27559122 TI - Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000-2010. AB - BACKGROUND: There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada. METHODS: We studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010. RESULTS: A total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000 2003, 2004-2007, and 2008-2010, respectively (Ptrend<.001); the rates of most individual OIs decreased as well. During 2008-2010, the leading OIs included Pneumocystis jiroveci pneumonia, esophageal candidiasis, and disseminated Mycobacterium avium complex or Mycobacterium kansasii infection. CONCLUSIONS: For HIV-infected persons in care during 2000-2010, rates of first OI were relatively low and generally declined over this time. PMID- 27559126 TI - MenaINV mediates synergistic cross-talk between signaling pathways driving chemotaxis and haptotaxis. AB - Directed cell migration, a key process in metastasis, arises from the combined influence of multiple processes, including chemotaxis-the directional movement of cells to soluble cues-and haptotaxis-the migration of cells on gradients of substrate-bound factors. However, it is unclear how chemotactic and haptotactic pathways integrate with each other to drive overall cell behavior. MenaINV has been implicated in metastasis by driving chemotaxis via dysregulation of phosphatase PTP1B and more recently in haptotaxis via interaction with integrin alpha5beta1. Here we find that MenaINV-driven haptotaxis on fibronectin (FN) gradients requires intact signaling between alpha5beta1 integrin and the epidermal growth factor receptor (EGFR), which is influenced by PTP1B. Furthermore, we show that MenaINV-driven haptotaxis and ECM reorganization both require the Rab-coupling protein RCP, which mediates alpha5beta1 and EGFR recycling. Finally, MenaINV promotes synergistic migratory response to combined EGF and FN in vitro and in vivo, leading to hyperinvasive phenotypes. Together our data demonstrate that MenaINV is a shared component of multiple prometastatic pathways that amplifies their combined effects, promoting synergistic cross-talk between RTKs and integrins. PMID- 27559127 TI - The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy. AB - The small GTPase Rab5 promotes recruitment of the Ccz1-Mon1 guanosine exchange complex to endosomes to activate Rab7, which facilitates endosome maturation and fusion with lysosomes. How these factors function during autophagy is incompletely understood. Here we show that autophagosomes accumulate due to impaired fusion with lysosomes upon loss of the Ccz1-Mon1-Rab7 module in starved Drosophila fat cells. In contrast, autophagosomes generated in Rab5-null mutant cells normally fuse with lysosomes during the starvation response. Consistent with that, Rab5 is dispensable for the Ccz1-Mon1-dependent recruitment of Rab7 to PI3P-positive autophagosomes, which are generated by the action of the Atg14 containing Vps34 PI3 kinase complex. Finally, we find that Rab5 is required for proper lysosomal function. Thus the Ccz1-Mon1-Rab7 module is required for autophagosome-lysosome fusion, whereas Rab5 loss interferes with a later step of autophagy: the breakdown of autophagic cargo within lysosomes. PMID- 27559128 TI - Xenopus TACC2 is a microtubule plus end-tracking protein that can promote microtubule polymerization during embryonic development. AB - Microtubule dynamics is regulated by plus end-tracking proteins (+TIPs), which localize to the plus ends of microtubules (MTs). We previously showed that TACC1 and TACC3, members of the transforming acidic coiled-coil protein family, can act as +TIPs to regulate MT dynamics in Xenopus laevis Here we characterize TACC2 as a +TIP that localizes to MT plus ends in front of EB1 and overlapping with TACC1 and TACC3 in multiple embryonic cell types. We also show that TACC2 can promote MT polymerization in mesenchymal cells but not neuronal growth cones, thus displaying cell-type specificity. Structure-function analysis demonstrates that the C-terminal region of TACC2 is both necessary and sufficient to localize to MT plus ends and promote increased rates of MT polymerization, whereas the N terminal region cannot bind to MT plus ends but can act in a dominant-negative capacity to reduce polymerization rates. Finally, we analyze mRNA expression patterns in Xenopus embryos for each TACC protein and observe neural enrichment of TACC3 expression compared with TACC1 and TACC2, which are also expressed in mesodermal tissues, including somites. Overall these data provide a novel assessment of all three TACC proteins as a family of +TIPs by highlighting the unique attributes of each, as well as their collective characteristics. PMID- 27559129 TI - Comparative analysis of adaptor-mediated clathrin assembly reveals general principles for adaptor clustering. AB - Clathrin-mediated endocytosis (CME) manages the sorting and uptake of the bulk of membrane proteins (or cargo) from the plasma membrane. CME is initiated by the formation of clathrin-coated pits (CCPs), in which adaptors nucleate clathrin assembly. Clathrin adaptors display diversity in both the type and number of evolutionarily conserved clathrin-binding boxes. How this diversity relates to the process of adaptor clustering as clathrin assembles around a growing pit remains unclear. Using real-time, fluorescence microscopy-based assays, we compare the formation kinetics and distribution of clathrin assemblies on membranes that display five unique clathrin adaptors. Correlations between equilibrium and kinetic parameters of clathrin assembly to the eventual adaptor distribution indicate that adaptor clustering is determined not by the amount of clathrin recruited or the degree of clathrin clustered but instead by the rate of clathrin assembly. Together our results emphasize the need to analyze kinetics of protein interactions to better understand mechanisms that regulate CME. PMID- 27559130 TI - Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53. AB - Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle progression. Acute polyploidy was generated by knockdown of the essential regulator of cytokinesis anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target, CDK inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single cell-derived, adapted tetraploid clones showed up-regulation of several p53 target genes and cyclin D2, the activator of CDK4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results indicate that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as cyclin D2, elucidating a possible route for tetraploidy mediated genomic instability in carcinogenesis. PMID- 27559131 TI - C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. AB - Hexanucleotide expansion in an intron of the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia. However, beyond bioinformatics predictions that suggested structural similarity to folliculin, the Birt-Hogg Dube syndrome tumor suppressor, little is known about the normal functions of the C9orf72 protein. To address this problem, we used genome-editing strategies to investigate C9orf72 interactions, subcellular localization, and knockout (KO) phenotypes. We found that C9orf72 robustly interacts with SMCR8 (a protein of previously unknown function). We also observed that C9orf72 localizes to lysosomes and that such localization is negatively regulated by amino acid availability. Analysis of C9orf72 KO, SMCR8 KO, and double-KO cell lines revealed phenotypes that are consistent with a function for C9orf72 at lysosomes. These include abnormally swollen lysosomes in the absence of C9orf72 and impaired responses of mTORC1 signaling to changes in amino acid availability (a lysosome dependent process) after depletion of either C9orf72 or SMCR8. Collectively these results identify strong physical and functional interactions between C9orf72 and SMCR8 and support a lysosomal site of action for this protein complex. PMID- 27559132 TI - Actin filaments as dynamic reservoirs for Drp1 recruitment. AB - Drp1 is a dynamin-family GTPase recruited to mitochondria and peroxisomes, where it oligomerizes and drives membrane fission. Regulation of mitochondrial Drp1 recruitment is not fully understood. We previously showed that Drp1 binds actin filaments directly, and actin polymerization is necessary for mitochondrial Drp1 oligomerization in mammals. Here we show the Drp1/actin interaction displays unusual properties that are influenced by several factors. At saturation, only a fraction Drp1 binds actin filaments, and the off-rate of actin-bound Drp1 is significantly increased by unbound Drp1. GDP and GTP accelerate and decelerate Drp1/actin binding dynamics, respectively. Actin has a biphasic effect on Drp1 GTP hydrolysis, increasing at low actin:Drp1 ratio but returning to baseline at high ratio. Drp1 also bundles filaments. Bundles have reduced dynamics but follow the same trends as single filaments. Drp1 preferentially incorporates into bundles at higher ionic strength. We measure Drp1 concentration to be ~0.5 MUM in U2OS cell cytosol, suggesting the actin-binding affinity measured here (Kd = 0.6 MUM) is in the physiologically relevant range. The ability of Drp1 to bind actin filaments in a highly dynamic manner provides potential for actin filaments to serve as reservoirs of oligomerization-competent Drp1 that can be accessed for mitochondrial fission. PMID- 27559133 TI - Assembly of Caenorhabditis elegans acentrosomal spindles occurs without evident microtubule-organizing centers and requires microtubule sorting by KLP-18/kinesin 12 and MESP-1. AB - Although centrosomes contribute to spindle formation in most cell types, oocytes of many species are acentrosomal and must organize spindles in their absence. Here we investigate this process in Caenorhabditis elegans, detailing how acentrosomal spindles form and revealing mechanisms required to establish bipolarity. Using high-resolution imaging, we find that in meiosis I, microtubules initially form a "cage-like" structure inside the disassembling nuclear envelope. This structure reorganizes so that minus ends are sorted to the periphery of the array, forming multiple nascent poles that then coalesce until bipolarity is achieved. In meiosis II, microtubules nucleate in the vicinity of chromosomes but then undergo similar sorting and pole formation events. We further show that KLP-18/kinesin-12 and MESP-1, previously shown to be required for spindle bipolarity, likely contribute to bipolarity by sorting microtubules. After their depletion, minus ends are not sorted outward at the early stages of spindle assembly and instead converge. These proteins colocalize on microtubules, are interdependent for localization, and can interact, suggesting that they work together. We propose that KLP-18/kinesin-12 and MESP-1 form a complex that functions to sort microtubules of mixed polarity into a configuration in which minus ends are away from the chromosomes, enabling formation of nascent poles. PMID- 27559134 TI - The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4. AB - The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5. PMID- 27559135 TI - Decoding the principles underlying the frequency of association with nucleoli for RNA polymerase III-transcribed genes in budding yeast. AB - The association of RNA polymerase III (Pol III)-transcribed genes with nucleoli seems to be an evolutionarily conserved property of the spatial organization of eukaryotic genomes. However, recent studies of global chromosome architecture in budding yeast have challenged this view. We used live-cell imaging to determine the intranuclear positions of 13 Pol III-transcribed genes. The frequency of association with nucleolus and nuclear periphery depends on linear genomic distance from the tethering elements-centromeres or telomeres. Releasing the hold of the tethering elements by inactivating centromere attachment to the spindle pole body or changing the position of ribosomal DNA arrays resulted in the association of Pol III-transcribed genes with nucleoli. Conversely, ectopic insertion of a Pol III-transcribed gene in the vicinity of a centromere prevented its association with nucleolus. Pol III-dependent transcription was independent of the intranuclear position of the gene, but the nucleolar recruitment of Pol III-transcribed genes required active transcription. We conclude that the association of Pol III-transcribed genes with the nucleolus, when permitted by global chromosome architecture, provides nucleolar and/or nuclear peripheral anchoring points contributing locally to intranuclear chromosome organization. PMID- 27559136 TI - Spatial regulation of astral microtubule dynamics by Kif18B in PtK cells. AB - The spatial and temporal control of microtubule dynamics is fundamentally important for proper spindle assembly and chromosome segregation. This is achieved, in part, by the multitude of proteins that bind to and regulate spindle microtubules, including kinesin superfamily members, which act as microtubule destabilizing enzymes. These fall into two general classes: the kinesin-13 proteins, which directly depolymerize microtubules, and the kinesin-8 proteins, which are plus end-directed motors that either destabilize microtubules or cap the microtubule plus ends. Here we analyze the contribution of a PtK kinesin-8 protein, Kif18B, in the control of mitotic microtubule dynamics. Knockdown of Kif18B causes defects in spindle microtubule organization and a dramatic increase in astral microtubules. Kif18B-knockdown cells had defects in chromosome alignment, but there were no defects in chromosome segregation. The long astral microtubules that occur in the absence of Kif18B are limited in length by the cell cortex. Using EB1 tracking, we show that Kif18B activity is spatially controlled, as loss of Kif18B has the most dramatic effect on the lifetimes of astral microtubules that extend toward the cell cortex. Together our studies provide new insight into how diverse kinesins contribute to spatial microtubule organization in the spindle. PMID- 27559137 TI - The duration of reaching movement is longer than predicted by minimum variance. AB - Whether the central nervous system minimizes variability or effort in planning arm movements can be tested by measuring the preferred movement duration and end point variability. Here we conducted an experiment in which subjects performed arm reaching movements without visual feedback in fast-, medium-, slow-, and preferred-duration conditions. Results show that 1) total end-point variance was smallest in the medium-duration condition and 2) subjects preferred to carry out movements that were slower than this medium-duration condition. A parsimonious explanation for the overall pattern of end-point errors across fast, medium, preferred, and slow movement durations is that movements are planned to minimize effort as well as end-point error due to both signal-dependent and constant noise. PMID- 27559138 TI - Hypoxia and hypercapnia inhibit hypothalamic orexin neurons in rats. AB - Evidence of impaired function of orexin neurons has been found in individuals with cardiorespiratory disorders, such as obstructive sleep apnea (OSA) and sudden infant death syndrome (SIDS), but the mechanisms responsible are unknown. Individuals with OSA and SIDS experience repetitive breathing cessations and/or rebreathing of expired air, resulting in hypoxia/hypercapnia (H/H). In this study, we examined the responses of fluorescently identified rat orexin neurons in the lateral hypothalamus to acute H/H to test if and how these neurons alter their activity and function during this challenge. Experiments were conducted in an in vitro slice preparation using voltage-clamp and current-clamp configurations. H/H (10 min) induced hyperpolarization, accompanied by rapid depression, and finally, cessation of firing activity in orexin neurons. Hypoxia alone had similar but less potent effects. H/H did not alter the frequency of inhibitory glycinergic postsynaptic currents. The frequency of GABAergic currents was diminished but only at 8-10 min of H/H. In contrast, the frequency of excitatory glutamatergic postsynaptic events was diminished as early as 2-4 min of H/H. In the presence of glutamatergic receptor blockers, the inhibitory effects of H/H on the firing activity and membrane potential of orexin neurons persisted but to a lesser extent. In conclusion, both direct alteration of postsynaptic membrane properties and diminished glutamatergic neurotransmission likely contribute to the inhibition of orexin neurons by H/H. These mechanisms could be responsible for the decreased function of orexin in individuals at risk for OSA and SIDS. PMID- 27559139 TI - A systematic analysis of neurons with large somatosensory receptive fields covering multiple body regions in the secondary somatosensory area of macaque monkeys. AB - Previous neurophysiological studies performed in macaque monkeys have revealed complex somatosensory responses in the secondary somatosensory area (SII), such as large receptive fields (RFs), as well as bilateral ones. However, systematic analyses of neurons with large RFs have not been performed. In the present study, we recorded single-unit activities in SII of awake macaque monkeys to investigate systematically large RFs by dividing the whole body into four body regions (head, trunk, forelimb, and hindlimb). Recorded neurons were classified into two types, according to whether the RFs were confined to one body region: single (n = 817) and combined (n = 282) body-region types. These two types were distinct in terms of the percentage of bilateral RFs: 55% in the single-region type and 90% in the combined type, demonstrating that two types of RF enlargement occur simultaneously in the combined type, namely, RF convergence from different body regions and RF convergence from both hemibodies. Among the combined-type RFs, two tendencies of RF convergence were found: 1) the distal parts of the limbs (i.e., hand and foot) and the mouth are interconnected, and 2) the trunk RFs extend continuously toward the distal parts of the limb and head to cover the entire body surface. Our distribution analysis on unfolded maps clarified that neurons having RFs with these two tendencies were distributed within specific subregions in SII. PMID- 27559141 TI - Dynamic compensation mechanism gives rise to period and duty-cycle level sets in oscillatory neuronal models. AB - Rhythmic oscillation in neurons can be characterized by various attributes, such as the oscillation period and duty cycle. The values of these features depend on the amplitudes of the participating ionic currents, which can be characterized by their maximum conductance values. Recent experimental and theoretical work has shown that the values of these attributes can be maintained constant for different combinations of two or more ionic currents of varying conductances, defining what is known as level sets in conductance space. In two-dimensional conductance spaces, a level set is a curve, often a line, along which a particular oscillation attribute value is conserved. In this work, we use modeling, dynamical systems tools (phase-space analysis), and numerical simulations to investigate the possible dynamic mechanisms responsible for the generation of period and duty-cycle levels sets in simplified (linearized and FitzHugh-Nagumo) and conductance-based (Morris-Lecar) models of neuronal oscillations. A simplistic hypothesis would be that the tonic balance between ionic currents with the same or opposite effective signs is sufficient to create level sets. According to this hypothesis, the dynamics of each ionic current during a given cycle are well captured by some constant quantity (e.g., maximal conductances), and the phase-plane diagrams are identical or are almost identical (e.g., cubic-like nullclines with the same maxima and minima) for different combinations of these maximal conductances. In contrast, we show that these mechanisms are dynamic and involve the complex interaction between the nonlinear voltage dependencies and the effective time scales at which the ionic current's dynamical variables operate. PMID- 27559140 TI - A neuronal lactate uptake inhibitor slows recovery of extracellular ion concentration changes in the hippocampal CA3 region by affecting energy metabolism. AB - Astrocyte-derived lactate supports pathologically enhanced neuronal metabolism, but its role under physiological conditions is still a matter of debate. Here, we determined the contribution of astrocytic neuronal lactate shuttle for maintenance of ion homeostasis and energy metabolism. We tested for the effects of alpha-cyano-4-hydroxycinnamic acid (4-CIN), which could interfere with energy metabolism by blocking monocarboxylate-transporter 2 (MCT2)-mediated neuronal lactate uptake, on evoked potentials, stimulus-induced changes in K+, Na+, Ca2+, and oxygen concentrations as well as on changes in flavin adenine dinucleotide (FAD) autofluorescence in the hippocampal area CA3. MCT2 blockade by 4-CIN reduced synaptically evoked but not antidromic population spikes. This effect was dependent on the activation of KATP channels indicating reduced neuronal ATP synthesis. By contrast, lactate receptor activation by 3,5-dihydroxybenzoic acid (3,5-DHBA) resulted in increased antidromic and orthodromic population spikes suggesting that 4-CIN effects are not mediated by lactate accumulation and subsequent activation of lactate receptors. Recovery kinetics of all ion transients were prolonged and baseline K+ concentration became elevated by blockade of lactate uptake. Lactate contributed to oxidative metabolism as both baseline respiration and stimulus-induced changes in Po2 were decreased, while FAD fluorescence increased likely due to a reduced conversion of FAD into FADH2 These data suggest that lactate shuttle contributes to regulation of ion homeostatsis and synaptic signaling even in the presence of ample glucose. PMID- 27559142 TI - Efficient Payload Delivery by a Bispecific Antibody-Drug Conjugate Targeting HER2 and CD63. AB - Antibody-drug conjugates (ADC) are designed to be stable in circulation and to release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, and degradation in tumor cells. Efficient internalization and routing to lysosomes where proteolysis can take place is therefore essential. For many cell surface proteins and carbohydrate structures on tumor cells, however, the magnitude of these processes is insufficient to allow for an effective ADC approach. We hypothesized that we could overcome this limitation by enhancing lysosomal ADC delivery via a bispecific antibody (bsAb) approach, in which one binding domain would provide tumor specificity, whereas the other binding domain would facilitate targeting to the lysosomal compartment. We therefore designed a bsAb in which one binding arm specifically targeted CD63, a protein that is described to shuttle between the plasma membrane and intracellular compartments, and combined it in a bsAb with a HER2 binding arm, which was selected as model antigen for tumor-specific binding. The resulting bsHER2xCD63his demonstrated strong binding, internalization and lysosomal accumulation in HER2-positive tumor cells, and minimal internalization into HER2-negative cells. By conjugating bsHER2xCD63his to the microtubule-disrupting agent duostatin-3, we were able to demonstrate potent cytotoxicity of bsHER2xCD63his-ADC against HER2-positive tumors, which was not observed with monovalent HER2- and CD63-specific ADCs. Our data demonstrate, for the first time, that intracellular trafficking of ADCs can be improved using a bsAb approach that targets the lysosomal membrane protein CD63 and provide a rationale for the development of novel bsADCs that combine tumor-specific targeting with targeting of rapidly internalizing antigens. Mol Cancer Ther; 15(11); 2688-97. (c)2016 AACR. PMID- 27559143 TI - Shedding New Light on the Platelet Storage Lesion. PMID- 27559144 TI - Multiple Functions of Protein Inhibitor of Activated STAT1 in Regulating Endothelial Cell Proliferation and Inflammation. PMID- 27559145 TI - Monocytes Chat With Atherosclerotic Lesions. PMID- 27559147 TI - Correction. PMID- 27559148 TI - Correction. PMID- 27559146 TI - Nanomedicine Meets microRNA: Current Advances in RNA-Based Nanotherapies for Atherosclerosis. AB - Cardiovascular disease (CVD) accounts for almost half of all deaths worldwide and has now surpassed infectious disease as the leading cause of death and disability in developing countries. At present, therapies such as low-density lipoprotein lowering statins and antihypertensive drugs have begun to bend the morality curve for coronary artery disease (CAD); yet, as we come to appreciate the more complex pathophysiological processes in the vessel wall, there is an opportunity to fine tune therapies to more directly target mechanisms that drive CAD. MicroRNAs (miRNAs) have been identified that control vascular cell homeostasis,(1-3) lipoprotein metabolism,(4-9) and inflammatory cell function.(10) Despite the importance of these miRNAs in driving atherosclerosis and vascular dysfunction, therapeutic modulation of miRNAs in a cell- and context-specific manner has been a challenge. In this review, we summarize the emergence of miRNA-based therapies as an approach to treat CAD by specifically targeting the pathways leading to the disease. We focus on the latest development of nanoparticles (NPs) as a means to specifically target the vessel wall and what the future of these nanomedicines may hold for the treatment of CAD. PMID- 27559149 TI - Differences in cumulus cell gene expression indicate the benefit of a pre maturation step to improve in-vitro bovine embryo production. AB - STUDY QUESTION: Does the gene expression profile of cumulus cells (CC) accompanying oocytes with different degrees of chromatin compaction within the germinal vesicle (GV) reflect the oocyte's quality and response in culture during in-vitro embryo production (IVP). SUMMARY ANSWER: The transcriptomic profile of the CC is related to oocyte competence, setting the stage for the development of customized pre-maturation strategies to improve IVP. WHAT IS KNOWN ALREADY: Oocytes complete the acquisition of their competence during antral follicle development. During this period, the chromatin configuration within the GV changes dynamically and is indicative of oocyte's developmental potential. The interactions between somatic and germ cells modulate chromatin morphology and function and are critical for acquisition of oocyte competence. STUDY DESIGN, SIZE, DURATION: Bovine cumulus-oocyte complexes (COC) were isolated from 0.5 to 6 mm antral follicles. Surrounding CC were separated from the oocyte and classified as GV0, GV1, GV2 and GV3 according to the degree of the oocyte's chromatin compaction. PARTICIPANTS/MATERIALS, SETTING, METHOD: RNA extracted from CC of each group was amplified and hybridized on a bovine embryo-specific 44 K Agilent slide. The CC_GV1, CC_GV2 and CC_GV3 classes were each hybridized against the CC_GV0 class, representing an early oocyte differentiation stage with poor development competence. The data were normalized and fold changes of the differentially expressed genes were determined. Microarray data were validated using quantitative RT-PCR on selected targets. Microarray data were further analyzed through: (i) between-group analysis (BGA), which classifies the samples according to their transcriptomic profiles; (ii) cluster analysis according to the expression profile of each gene; and (iii) Ingenuity Pathway Analysis (IPA) to study gene regulation patterns and predicted functions. Furthermore, CC of each GV group were cultured and apoptotic cells were assessed after 3 h by caspase analysis. Finally, based on the analysis of CC transcriptomic profiles and the relationship between morphological features of the COC and the oocyte chromatin configuration, a customized, stage-dependent oocyte pre-maturation (pre IVM) system was used to improve oocyte developmental potential before IVM. For this, the blastocyst rate and quality were assessed after in-vitro maturation and fertilization of pre-matured oocytes. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, quantitative RT-PCR results of a subset of five selected genes were consistent with the microarray data. Clustering analysis generated 16 clusters representing the main profiles of transcription modulation. Of the 5571 significantly differentially expressed probes, the majority (25.49%) best fitted with cluster #6 (downregulation between CC_GV0 and CC_GV1 and stable low levels in successive groups). IPA identified the most relevant functions associated with each cluster. Genes included in cluster #1 were mostly related to biological processes such as 'cell cycle' and 'cell death and survival', whereas genes included in cluster #5 were mostly related to 'gene expression'. Interestingly, 'lipid metabolism' was the most significant function identified in clusters #6, #9 and #12. IPA of gene lists obtained from each contrast (i.e., CC_GV0 vs. CC_GV1; CC_GV0 vs. CC_GV2; CC_GV0 vs. CC_GV3) revealed that the main affected function in each contrast was 'cell death and survival'. Importantly, apoptosis was predicted to be inhibited in CC_GV1 and CC_GV2, but activated in CC_GV3. Caspase analysis indicated that a low percentage of CC_GV0 was prone to undergo apoptosis but apoptosis increased significantly in CC from oocytes with condensed chromatin, reaching a peak in CC_GV3 (P < 0.05). Finally, the tailored oocyte pre maturation strategy, based on morphological features of the COC and the oocyte chromatin configuration, demonstrated that pre-IVM improved the developmental capability of oocytes at early stages of differentiation (GV1-enriched COC) but was detrimental for oocytes at more advanced stages of development (GV2 and GV3 enriched COC). LARGE SCALE DATA: The data are available through the GEO series accession number GSE79886. LIMITATIONS, REASONS FOR CAUTION: This study was conducted with bovine samples. Whether or not the results are applicable to human oocytes requests further elucidation. Embryo transfer experiments are required to determine whether the improvement in blastocyst rates in the tailored system leads to increased live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: The identification of multiple non-invasive biomarkers predictive of oocyte quality can greatly strengthen the pre-IVM approach aimed to improve IVM outcomes. These results have potentially important implications in treating human infertility and in developing breeding schemes for domestic mammals. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by NSERC Strategic Network EmbryoGENE, Canada and in part by CIG-Marie Curie Actions-Reintegration Grants within the EU 7FP (n. 303640, 'Pro-Ovum'). The authors declare no potential conflict of interest. PMID- 27559150 TI - Corrections to "Molecular interaction of alpha-conotoxin RgIA with the rat alpha9alpha10 nicotinic acetylcholine receptor". PMID- 27559152 TI - Characterization of MinION nanopore data for resequencing analyses. AB - The Oxford Nanopore Technologies MinION is a new device, based on nanopore sequencing that is able to generate reads of tens of kilobases in length with faster sequencing time with respect to other platforms. To evaluate the capability of nanopore data to be exploited for resequencing analyses we used the largest MinION data set to date and we compared with Illumina and Pacific Biosciences technologies. By using five different mapping approaches we estimated that the global sequencing error rate of MinION reads, mainly caused by inserted and deleted bases, is around 11%. The study of error distribution showed that substituted, inserted and deleted bases are not randomly distributed along the reads, but mainly occur in specific nucleotide patterns, generating a significant number of genomic loci that can be misclassified as false-positive variants. With 40* sequencing coverage, MinION data can produce at best around one false substitution and insertion every 10-50 kb, and one false deletion every 1000 bp, making use of this technology still challenging for small-sized variant discovery. We also analyzed depth of coverage distribution and we demonstrated that nanopore sequencing is a uniform process that generates sequences randomly and independently without classical sources of bias such as GC-content and mappability. Owing to these properties, the MinION data can be readily used to detect genomic regions involved in copy number variants with high accuracy, outperforming other state-of-the-art sequencing methods in terms of both sensitivity and specificity. PMID- 27559153 TI - Discoal: flexible coalescent simulations with selection. AB - : Here we describe discoal, a coalescent simulator able to generate population samples that include selective sweeps in a feature-rich, flexible manner. discoal can perform simulations conditioning on the fixation of an allele due to drift or either hard or soft sweeps-even those occurring a large genetic distance away from the simulated locus. discoal can simulate sweeps with recurrent mutation to the adaptive allele, recombination, and gene conversion, under non-equilibrium demographic histories and without specifying an allele frequency trajectory in advance. AVAILABILITY AND IMPLEMENTATION: discoal is implemented in the C programming language. Source code is freely available on GitHub (https://github.com/kern-lab/discoal) under a GNU General Public License. CONTACT: kern@dls.rutgers.edu or dan.schrider@rutgers.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27559151 TI - A network medicine approach to build a comprehensive atlas for the prognosis of human cancer. AB - The Cancer Genome Atlas project has generated multi-dimensional and highly integrated genomic data from a large number of patient samples with detailed clinical records across many cancer types, but it remains unclear how to best integrate the massive amount of genomic data into clinical practice. We report here our methodology to build a multi-dimensional subnetwork atlas for cancer prognosis to better investigate the potential impact of multiple genetic and epigenetic (gene expression, copy number variation, microRNA expression and DNA methylation) changes on the molecular states of networks that in turn affects complex cancer survivorship. We uncover an average of 38 novel subnetworks in the protein-protein interaction network that correlate with prognosis across four prominent cancer types. The clinical utility of these subnetwork biomarkers was further evaluated by prognostic impact evaluation, functional enrichment analysis, drug target annotation, tumor stratification and independent validation. Some pathways including the dynactin, cohesion and pyruvate dehydrogenase-related subnetworks are identified as promising new targets for therapy in specific cancer types. In conclusion, this integrative analysis of existing protein interactome and cancer genomics data allows us to systematically dissect the molecular mechanisms that underlie unexpected outcomes for cancer, which could be used to better understand and predict clinical outcomes, optimize treatment and to provide new opportunities for developing therapeutics related to the subnetworks identified. PMID- 27559154 TI - Cas-analyzer: an online tool for assessing genome editing results using NGS data. AB - : Genome editing with programmable nucleases has been widely adopted in research and medicine. Next generation sequencing (NGS) platforms are now widely used for measuring the frequencies of mutations induced by CRISPR-Cas9 and other programmable nucleases. Here, we present an online tool, Cas-Analyzer, a JavaScript-based implementation for NGS data analysis. Because Cas-Analyzer is completely used at a client-side web browser on-the-fly, there is no need to upload very large NGS datasets to a server, a time-consuming step in genome editing analysis. Currently, Cas-Analyzer supports various programmable nucleases, including single nucleases and paired nucleases. AVAILABILITY AND IMPLEMENTATION: Free access at http://www.rgenome.net/cas-analyzer/ CONTACT: sangsubae@hanyang.ac.kr or jskim01@snu.ac.krSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27559155 TI - Fast-SNP: a fast matrix pre-processing algorithm for efficient loopless flux optimization of metabolic models. AB - MOTIVATION: Computation of steady-state flux solutions in large metabolic models is routinely performed using flux balance analysis based on a simple LP (Linear Programming) formulation. A minimal requirement for thermodynamic feasibility of the flux solution is the absence of internal loops, which are enforced using 'loopless constraints'. The resulting loopless flux problem is a substantially harder MILP (Mixed Integer Linear Programming) problem, which is computationally expensive for large metabolic models. RESULTS: We developed a pre-processing algorithm that significantly reduces the size of the original loopless problem into an easier and equivalent MILP problem. The pre-processing step employs a fast matrix sparsification algorithm-Fast- sparse null-space pursuit (SNP) inspired by recent results on SNP. By finding a reduced feasible 'loop-law' matrix subject to known directionalities, Fast-SNP considerably improves the computational efficiency in several metabolic models running different loopless optimization problems. Furthermore, analysis of the topology encoded in the reduced loop matrix enabled identification of key directional constraints for the potential permanent elimination of infeasible loops in the underlying model. Overall, Fast-SNP is an effective and simple algorithm for efficient formulation of loop-law constraints, making loopless flux optimization feasible and numerically tractable at large scale. AVAILABILITY AND IMPLEMENTATION: Source code for MATLAB including examples is freely available for download at http://www.aibn.uq.edu.au/cssb-resources under Software. Optimization uses Gurobi, CPLEX or GLPK (the latter is included with the algorithm). CONTACT: lars.nielsen@uq.edu.auSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27559156 TI - KScons: a Bayesian approach for protein residue contact prediction using the knob socket model of protein tertiary structure. AB - MOTIVATION: By simplifying the many-bodied complexity of residue packing into patterns of simple pairwise secondary structure interactions between a single knob residue with a three-residue socket, the knob-socket construct allows a more direct incorporation of structural information into the prediction of residue contacts. By modeling the preferences between the amino acid composition of a socket and knob, we undertake an investigation of the knob-socket construct's ability to improve the prediction of residue contacts. The statistical model considers three priors and two posterior estimations to better understand how the input data affects predictions. This produces six implementations of KScons that are tested on three sets: PSICOV, CASP10 and CASP11. We compare against the current leading contact prediction methods. RESULTS: The results demonstrate the usefulness as well as the limits of knob-socket based structural modeling of protein contacts. The construct is able to extract good predictions from known structural homologs, while its performance degrades when no homologs exist. Among our six implementations, KScons MST-MP (which uses the multiple structure alignment prior and marginal posterior incorporating structural homolog information) performs the best in all three prediction sets. An analysis of recall and precision finds that KScons MST-MP improves accuracy not only by improving identification of true positives, but also by decreasing the number of false positives. Over the CASP10 and CASP11 sets, KScons MST-MP performs better than the leading methods using only evolutionary coupling data, but not quite as well as the supervised learning methods of MetaPSICOV and CoinDCA-NN that incorporate a large set of structural features. CONTACT: qiwei.li@rice.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27559157 TI - PhenomeScape: a cytoscape app to identify differentially regulated sub-networks using known disease associations. AB - : PhenomeScape is a Cytoscape app which provides easy access to the PhenomeExpress algorithm to interpret gene expression data. PhenomeExpress integrates protein interaction networks with known phenotype to gene associations to find active sub-networks enriched in differentially expressed genes. It also incorporates cross-species phenotypes and associations to include results from animal models of disease. With expression data imported into PhenomeScape, the user can quickly generate and visualise interactive sub-networks. PhenomeScape thus enables researchers to use prior knowledge of a disease to identify differentially regulated sub-networks and to generate an overview of altered biologically processes specific to that disease. AVAILABILITY AND IMPLEMENTATION: Freely available for download at https://github.com/soulj/PhenomeScape CONTACT: jamie.soul@postgrad.manchester.ac.uk or jean-marc.schwartz@manchester.ac.uk. PMID- 27559158 TI - AlmostSignificant: simplifying quality control of high-throughput sequencing data. AB - MOTIVATION: The current generation of DNA sequencing technologies produce a large amount of data quickly. All of these data need to pass some form of quality control (QC) processing and checking before they can be used for any analysis. The large number of samples that are run through Illumina sequencing machines makes the process of QC an onerous and time-consuming task that requires multiple pieces of information from several sources. RESULTS: AlmostSignificant is an open source platform for aggregating multiple sources of quality metrics as well as run and sample meta-data associated with DNA sequencing runs from Illumina sequencing machines. AlmostSignificant is a graphical platform to streamline the QC of DNA sequencing data, to store these data for future reference together with extra meta-data associated with the sequencing runs not typically retained. This simplifies the challenge of monitoring the volume of data produced by Illumina sequencers. AlmostSignificant has been used to track the quality of over 80 sequencing runs covering over 2500 samples produced over the last three years. AVAILABILITY AND IMPLEMENTATION: The code and documentation for AlmostSignificant is freely available at https://github.com/bartongroup/AlmostSignificant CONTACTS: c.cole@dundee.ac.uk or g.j.barton@dundee.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27559160 TI - Impaired Cardiorespiratory Function during Focal Limbic Seizures: A Role for Serotonergic Brainstem Nuclei. PMID- 27559159 TI - Assembly-based inference of B-cell receptor repertoires from short read RNA sequencing data with V'DJer. AB - MOTIVATION: B-cell receptor (BCR) repertoire profiling is an important tool for understanding the biology of diverse immunologic processes. Current methods for analyzing adaptive immune receptor repertoires depend upon PCR amplification of VDJ rearrangements followed by long read amplicon sequencing spanning the VDJ junctions. While this approach has proven to be effective, it is frequently not feasible due to cost or limited sample material. Additionally, there are many existing datasets where short-read RNA sequencing data are available but PCR amplified BCR data are not. RESULTS: We present here V'DJer, an assembly-based method that reconstructs adaptive immune receptor repertoires from short-read RNA sequencing data. This method captures expressed BCR loci from a standard RNA-seq assay. We applied this method to 473 Melanoma samples from The Cancer Genome Atlas and demonstrate V'DJer's ability to accurately reconstruct BCR repertoires from short read mRNA-seq data. AVAILABILITY AND IMPLEMENTATION: V'DJer is implemented in C/C ++, freely available for academic use and can be downloaded from Github: https://github.com/mozack/vdjer CONTACT: benjamin_vincent@med.unc.edu or parkerjs@email.unc.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27559161 TI - Social Stress-Induced Alterations in CRF Signaling in the VTA Facilitate the Emergence of Addiction-like Behavior. PMID- 27559162 TI - Neuromuscular NMDA Receptors Modulate Developmental Synapse Elimination. AB - At birth, each mammalian skeletal muscle fiber is innervated by multiple motor neurons, but in a few weeks, all but one of those axons retracts (Redfern, 1970) and differential activity between inputs controls this phenomenon (Personius and Balice-Gordon, 2001; Sanes and Lichtman, 2001; Personius et al., 2007; Favero et al., 2012). Acetylcholine, the primary neuromuscular transmitter, has long been presumed to mediate this activity-dependent process (O'Brien et al., 1978), but glutamatergic transmission also occurs at the neuromuscular junction (Berger et al., 1995; Grozdanovic and Gossrau, 1998; Mays et al., 2009). To test the role of neuromuscular NMDA receptors, we assessed their contribution to muscle calcium fluxes in mice and tested whether they influence removal of excess innervation at the end plate. Developmental synapse pruning was slowed by reduction of NMDA receptor activation or expression and by reduction of glutamate production. Conversely, pruning is accelerated by application of exogenous NMDA. We also found that NMDA induced increased muscle calcium only during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and synaptic pruning during development. SIGNIFICANCE STATEMENT: In normal adult muscle, each muscle fiber is innervated by a single axon, but at birth, fibers are multiply innervated. Elimination of excess connections requires neural activity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been assumed to be the critical mediator of activity. However, glutamate receptors are also expressed at the NMJ. We found that axon removal in mice is slowed by pharmacological and molecular manipulations that decrease signaling through neuromuscular NMDA receptors, whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle calcium levels during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and elimination of excess synaptic input during development. PMID- 27559163 TI - Mutant Huntingtin Impairs BDNF Release from Astrocytes by Disrupting Conversion of Rab3a-GTP into Rab3a-GDP. AB - Brain-derived neurotrophic factor (BDNF) is essential for neuronal differentiation and survival. We know that BDNF levels decline in the brains of patients with Huntington's disease (HD), a neurodegenerative disease caused by the expression of mutant huntingtin protein (mHtt), and furthermore that administration of BDNF in HD mice is protective against HD neuropathology. BDNF is produced in neurons, but astrocytes are also an important source of BDNF in the brain. Nonetheless, whether mHtt affects astrocytic BDNF in the HD brain remains unknown. Here we investigated astrocytes from HD140Q knock-in mice and uncovered evidence that mHtt decreases BDNF secretion from astrocytes, which is mediated by exocytosis in astrocytes. Our results demonstrate that mHtt associates with Rab3a, a small GTPase localized on membranes of dense-core vesicles, and prevents GTP-Rab3a from binding to Rab3-GAP1, disrupting the conversion of GTP-Rab3a into GDP-Rab3a and thus impairing the docking of BDNF vesicles on plasma membranes of astrocytes. Importantly, overexpression of Rab3a rescues impaired BDNF vesicle docking and secretion from HD astrocytes. Moreover, ATP release and the number of ATP-containing dense-core vesicles docking are decreased in HD astrocytes, suggesting that the exocytosis of dense-core vesicles is impaired by mHtt in HD astrocytes. Further, Rab3a overexpression reduces reactive astrocytes in the striatum of HD140Q knock-in mice. Our results indicate that compromised exocytosis of BDNF in HD astrocytes contributes to the decreased BDNF levels in HD brains and underscores the importance of improving glial function in the treatment of HD. SIGNIFICANCE STATEMENT: Huntington's disease (HD) is an inherited neurodegenerative disorder that affects one in every 10,000 Americans. To date, there is no effective treatment for HD, in part because the pathogenic mechanism driving the disease is not fully understood. The dysfunction of astrocytes is known to contribute to the pathogenesis of HD. One important role of astrocytes is to synthesize and release brain-derived neurotrophic factor (BDNF), which is vital for neuronal survival, development, and function. We found that mutant huntingtin protein (mHtt) at the endogenous level decreases BDNF secretion from astrocytes by disrupting the conversion of GTP-Rab3a into GDP Rab3a and that overexpressing Rab3a can rescue this deficient BDNF release and early neuropathology in HD knock-in mouse brain. Our study suggests that astrocytic Rab3a is a potential therapeutic target for HD treatment. PMID- 27559164 TI - mGluR5 Exerts Cell-Autonomous Influences on the Functional and Anatomical Development of Layer IV Cortical Neurons in the Mouse Primary Somatosensory Cortex. AB - Glutamate neurotransmission refines synaptic connections to establish the precise neural circuits underlying sensory processing. Deleting metabotropic glutamate receptor 5 (mGluR5) in mice perturbs cortical somatosensory map formation in the primary somatosensory (S1) cortex at both functional and anatomical levels. To examine the cell-autonomous influences of mGluR5 signaling in the morphological and functional development of layer IV spiny stellate glutamatergic neurons receiving sensory input, mGluR5 genetic mosaic mice were generated through in utero electroporation. In the S1 cortex of these mosaic brains, we found that most wild-type neurons were located in barrel rings encircling thalamocortical axon (TCA) clusters while mGluR5 knock-out (KO) neurons were placed in the septal area, the cell-sparse region separating barrels. These KO neurons often displayed a symmetrical dendritic morphology with increased dendritic complexity, in contrast to the polarized pattern of wild-type neurons. The dendritic spine density of mGluR5 KO spiny stellate neurons was significantly higher than in wild type neurons. Whole-cell electrophysiological recordings detected a significant increase in the frequencies of spontaneous and miniature excitatory postsynaptic events in mGluR5 KO neurons compared with neighboring wild-type neurons. Our mosaic analysis provides strong evidence supporting the cell-autonomous influence of mGluR5 signaling on the functional and anatomical development of cortical glutamatergic neurons. Specifically, mGluR5 is required in cortical glutamatergic neurons for the following processes: (1) the placement of cortical glutamatergic neurons close to TCA clusters; (2) the regulation of dendritic complexity and outgrowth toward TCA clusters; (3) spinogenesis; and (4) tuning of excitatory inputs. SIGNIFICANCE STATEMENT: Glutamatergic transmission plays a critical role in cortical circuit formation. Its dysfunction has been proposed as a core factor in the etiology of many neurological diseases. Here we conducted mosaic analysis to reveal the cell-autonomous role of the metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5 is required for several key steps in wiring up the thalamocortical connections to form the cortical somatosensory map. mGluR5 dependent processes during early postnatal brain development affect the following: (1) placement of activity-directed cortical neurons; (2) regulation of polarized dendritic outgrowth toward thalamocortical axons relaying sensory information, (3) synaptogenesis; and (4) development of functional connectivity in spiny stellate neurons. Perturbing mGluR5 expression could lead to abnormal neuronal circuits, which may contribute to neurological and psychiatric disease. PMID- 27559165 TI - Chimeric Glutamate Receptor Subunits Reveal the Transmembrane Domain Is Sufficient for NMDA Receptor Pore Properties but Some Positive Allosteric Modulators Require Additional Domains. AB - NMDA receptors are ligand-gated ion channels that underlie transmission at excitatory synapses and play an important role in regulating synaptic strength and stability. Functional NMDA receptors require two copies of the GluN1 subunit coassembled with GluN2 (and/or GluN3) subunits into a heteromeric tetramer. A diverse array of allosteric modulators can upregulate or downregulate NMDA receptor activity. These modulators include both synthetic compounds and endogenous modulators, such as cis-unsaturated fatty acids, 24(S) hydroxycholesterol, and various neurosteroids. To evaluate the structural requirements for the formation and allosteric modulation of NMDA receptor pores, we have replaced portions of the rat GluN1, GluN2A, and GluN2B subunits with homologous segments from the rat GluK2 kainate receptor subunit. Our results with these chimeric constructs show that the NMDA receptor transmembrane domain is sufficient to account for most pore properties, but that regulation by some allosteric modulators requires additional cytoplasmic or extracellular domains. SIGNIFICANCE STATEMENT: Glutamate receptors mediate excitatory synaptic transmission by forming cation channels through the membrane that open upon glutamate binding. Although many compounds have been identified that regulate glutamate receptor activity, in most cases the detailed mechanisms that underlie modulation are poorly understood. To identify what parts of the receptor are essential for pore formation and sensitivity to allosteric modulators, we generated chimeric subunits that combined segments from NMDA and kainate receptors, subtypes with distinct pharmacological profiles. Surprisingly, our results identify separate domain requirements for allosteric potentiation of NMDA receptor pores by pregnenolone sulfate, 24(S)-hydroxycholesterol, and docosahexaenoic acid, three endogenous modulators derived from membrane constituents. Understanding where and how these compounds act on NMDA receptors should aid in designing better therapeutic agents. PMID- 27559166 TI - p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy. AB - In many diseases, expression and ligand-dependent activity of the p75(NTR) receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75(NTR) may be implicated at each stage of DR pathology remain poorly understood. Using a streptozotocin mouse model of diabetic retinopathy, we report that p75(NTR) is upregulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood-retina barrier breakdown, edema, and neuronal death. In a mouse model of oxygen-induced retinopathy, mimicking proliferative DR, p75(NTR) dependent inflammation leads to ischemia and pathological angiogenesis through Semaphorin 3A. The acute use of antagonists of p75(NTR) or antagonists of the ligand proNGF suppresses each distinct phase of pathology, ameliorate disease, and prevent disease progression. Thus, our study documents novel disease mechanisms and validates druggable targets for diabetic retinopathy. SIGNIFICANCE STATEMENT: Diabetic retinopathy (DR) affects an estimated 250 million people and has no effective treatment. Stages of progression comprise pericyte/vascular dysfunction, inflammation, glial activation, and neurodegeneration. The pathophysiology of each stage remains unclear. We postulated that the activity of p75NTR may be implicated. We show that p75NTR in glia and in pericytes mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro glia-vascular unit, promotion of blood-retina barrier breakdown, edema, and neuronal death. p75NTR-promoted inflammation leads to ischemia and angiogenesis through Semaphorin 3A. Antagonists of p75NTR or antagonists of proNGF suppress each distinct phase of pathology, ameliorate disease, and prevent disease progression. Our study documents novel mechanisms in a pervasive disease and validates druggable targets for treatment. PMID- 27559167 TI - Partial Breakdown of Input Specificity of STDP at Individual Synapses Promotes New Learning. AB - Hebbian-type learning rules, which underlie learning and refinement of neuronal connectivity, postulate input specificity of synaptic changes. However, theoretical analyses have long appreciated that additional mechanisms, not restricted to activated synapses, are needed to counteract positive feedback imposed by Hebbian-type rules on synaptic weight changes and to achieve stable operation of learning systems. The biological basis of such mechanisms has remained elusive. Here we show that, in layer 2/3 pyramidal neurons from slices of visual cortex of rats, synaptic changes induced at individual synapses by spike timing-dependent plasticity do not strictly follow the input specificity rule. Spike timing-dependent plasticity is accompanied by changes in unpaired synapses: heterosynaptic plasticity. The direction of heterosynaptic changes is weight-dependent, with balanced potentiation and depression, so that the total synaptic input to a cell remains preserved despite potentiation or depression of individual synapses. Importantly, this form of heterosynaptic plasticity is induced at unpaired synapses by the same pattern of postsynaptic activity that induces homosynaptic changes at paired synapses. In computer simulations, we show that experimentally observed heterosynaptic plasticity can indeed serve the theoretically predicted role of robustly preventing runaway dynamics of synaptic weights and activity. Moreover, it endows model neurons and networks with essential computational features: enhancement of synaptic competition, facilitation of the development of specific intrinsic connectivity, and the ability for relearning. We conclude that heterosynaptic plasticity is an inherent property of plastic synapses, crucial for normal operation of learning systems. SIGNIFICANCE STATEMENT: We show that spike timing-dependent plasticity in L2/L3 pyramids from rat visual cortex is accompanied by plastic changes in unpaired synapses. These heterosynaptic changes are weight-dependent and balanced: individual synapses expressed significant LTP or LTD, but the average over all synapses did not change. Thus, the rule of input specificity breaks down at individual synapses but holds for responses averaged over many inputs. In model neurons and networks, this experimentally characterized form of heterosynaptic plasticity prevents runaway dynamics of synaptic weights and activity, enhances synaptic competition, facilitates development of specific intrinsic connectivity, and enables relearning. This new form of heterosynaptic plasticity represents the cellular basis of a theoretically postulated mechanism, which is additional to Hebbian-type rules, and is necessary for stable operation of learning systems. PMID- 27559169 TI - Neural Basis of Acquired Amusia and Its Recovery after Stroke. AB - Although acquired amusia is a relatively common disorder after stroke, its precise neuroanatomical basis is still unknown. To evaluate which brain regions form the neural substrate for acquired amusia and its recovery, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study with 77 human stroke subjects. Structural MRIs were acquired at acute and 6 month poststroke stages. Amusia and aphasia were behaviorally assessed at acute and 3 month poststroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA) and language tests. VLSM analyses indicated that amusia was associated with a lesion area comprising the superior temporal gyrus, Heschl's gyrus, insula, and striatum in the right hemisphere, clearly different from the lesion pattern associated with aphasia. Parametric analyses of MBEA Pitch and Rhythm scores showed extensive lesion overlap in the right striatum, as well as in the right Heschl's gyrus and superior temporal gyrus. Lesions associated with Rhythm scores extended more superiorly and posterolaterally. VBM analysis of volume changes from the acute to the 6 month stage showed a clear decrease in gray matter volume in the right superior and middle temporal gyri in nonrecovered amusic patients compared with nonamusic patients. This increased atrophy was more evident in anterior temporal areas in rhythm amusia and in posterior temporal and temporoparietal areas in pitch amusia. Overall, the results implicate right temporal and subcortical regions as the crucial neural substrate for acquired amusia and highlight the importance of different temporal lobe regions for the recovery of amusia after stroke. SIGNIFICANCE STATEMENT: Lesion studies are essential in uncovering the brain regions causally linked to a given behavior or skill. For music perception ability, previous lesion studies of amusia have been methodologically limited in both spatial accuracy and time domain as well as by small sample sizes, providing coarse and equivocal information about which brain areas underlie amusia. By using longitudinal MRI and behavioral data from a large sample of stroke patients coupled with modern voxel-based analyses methods, we were able provide the first systematic evidence for the causal role of right temporal and striatal areas in music perception. Clinically, these results have important implications for the diagnosis and prognosis of amusia after stroke and for rehabilitation planning. PMID- 27559168 TI - Task Learning Promotes Plasticity of Interneuron Connectivity Maps in the Olfactory Bulb. AB - Elucidating patterns of functional synaptic connectivity and deciphering mechanisms of how plasticity influences such connectivity is essential toward understanding brain function. In the mouse olfactory bulb (OB), principal neurons (mitral/tufted cells) make reciprocal connections with local inhibitory interneurons, including granule cells (GCs) and external plexiform layer (EPL) interneurons. Our current understanding of the functional connectivity between these cell types, as well as their experience-dependent plasticity, remains incomplete. By combining acousto-optic deflector-based scanning microscopy and genetically targeted expression of Channelrhodopsin-2, we mapped connections in a cell-type-specific manner between mitral cells (MCs) and GCs or between MCs and EPL interneurons. We found that EPL interneurons form broad patterns of connectivity with MCs, whereas GCs make more restricted connections with MCs. Using an olfactory associative learning paradigm, we found that these circuits displayed differential features of experience-dependent plasticity. Whereas reciprocal connectivity between MCs and EPL interneurons was nonplastic, the connections between GCs and MCs were dynamic and adaptive. Interestingly, experience-dependent plasticity of GCs occurred only in certain stages of neuronal maturation. We show that different interneuron subtypes form distinct connectivity maps and modes of experience-dependent plasticity in the OB, which may reflect their unique functional roles in information processing. SIGNIFICANCE STATEMENT: Deducing how specific interneuron subtypes contribute to normal circuit function requires understanding the dynamics of their connections. In the olfactory bulb (OB), diverse interneuron subtypes vastly outnumber principal excitatory cells. By combining acousto-optic deflector-based scanning microscopy, electrophysiology, and genetically targeted expression of Channelrhodopsin-2, we mapped the functional connectivity between mitral cells (MCs) and OB interneurons in a cell-type-specific manner. We found that, whereas external plexiform layer (EPL) interneurons show broadly distributed patterns of stable connectivity with MCs, adult-born granule cells show dynamic and plastic patterns of synaptic connectivity with task learning. Together, these findings reveal the diverse roles for interneuons within sensory circuits toward information learning and processing. PMID- 27559171 TI - Differential Contributions of GABA Concentration in Frontal and Parietal Regions to Individual Differences in Attentional Blink. AB - Selective attention plays an important role in identifying transient objects in a complex visual scene. Attentional control ability varies with observers. However, it is unclear what neural mechanisms are responsible for individual differences in attentional control ability. The present study used the following attentional blink paradigm: when two targets are to be identified in rapid serial visual presentation, the processing of the first target interrupts the identification of the second one appearing within 500 ms after the first-target onset. It has been assumed that the reduction of the second-target accuracy is mainly due to a transient inhibition of attentional reorienting from the first to the second target, which is modulated by the GABA system. Using magnetic resonance spectroscopy, we investigated whether individual variation of attentional blink magnitude is associated with GABA concentrations in the left prefrontal cortex (PFC), right posterior-parietal cortex (PPC), and visual cortex (VC) of humans. GABA concentrations in the PFC were related negatively to attentional blink magnitude and positively to the first-target accuracy. GABA concentrations in the PPC were positively correlated with attentional blink magnitude. However, GABA concentrations in the VC did not contribute to attentional blink magnitude and first-target accuracy. Our results suggest that frontoparietal inhibitory mechanisms are closely linked with individual differences in attentional processing and that functional roles of the GABAergic system in selective attention differ between the PFC and PPC. SIGNIFICANCE STATEMENT: Selective attention is the process of picking up task-relevant information in the environment. Attentional blink reflects time constraints of visual attention. It has been assumed that attentional blink is induced by the inhibition of attentional reorienting to other objects. This study used magnetic resonance spectroscopy to noninvasively measure concentrations of GABA, the principal inhibitory neurotransmitter, in the human brain. We show that a neural interaction between GABA concentrations in the prefrontal and posterior parietal regions accounts for the interindividual variability of attentional blink magnitude. Our results provide direct evidence that the GABAergic system in the frontoparietal networks is responsible for temporal aspects of attentional control ability. PMID- 27559170 TI - Phosphorylation of Synaptojanin Differentially Regulates Endocytosis of Functionally Distinct Synaptic Vesicle Pools. AB - The rapid replenishment of synaptic vesicles through endocytosis is crucial for sustaining synaptic transmission during intense neuronal activity. Synaptojanin (Synj), a phosphoinositide phosphatase, is known to play an important role in vesicle recycling by promoting the uncoating of clathrin following synaptic vesicle uptake. Synj has been shown to be a substrate of the minibrain (Mnb) kinase, a fly homolog of the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A); however, the functional impacts of Synj phosphorylation by Mnb are not well understood. Here we identify that Mnb phosphorylates Synj at S1029 in Drosophila We find that phosphorylation of Synj at S1029 enhances Synj phosphatase activity, alters interaction between Synj and endophilin, and promotes efficient endocytosis of the active cycling vesicle pool (also referred to as exo-endo cycling pool) at the expense of reserve pool vesicle endocytosis. Dephosphorylated Synj, on the other hand, is deficient in the endocytosis of the active recycling pool vesicles but maintains reserve pool vesicle endocytosis to restore total vesicle pool size and sustain synaptic transmission. Together, our findings reveal a novel role for Synj in modulating reserve pool vesicle endocytosis and further indicate that dynamic phosphorylation and dephosphorylation of Synj differentially maintain endocytosis of distinct functional synaptic vesicle pools. SIGNIFICANCE STATEMENT: Synaptic vesicle endocytosis sustains communication between neurons during a wide range of neuronal activities by recycling used vesicle membrane and protein components. Here we identify that Synaptojanin, a protein with a known role in synaptic vesicle endocytosis, is phosphorylated at S1029 in vivo by the Minibrain kinase. We further demonstrate that the phosphorylation status of Synaptojanin at S1029 differentially regulates its participation in the recycling of distinct synaptic vesicle pools. Our results reveal a new role for Synaptojanin in maintaining synaptic vesicle pool size and in reserve vesicle endocytosis. As Synaptojanin and Minibrain perturbations are associated with various neurological disorders, such as Parkinson's, autism, and Down syndrome, understanding mechanisms modulating Synaptojanin function provides valuable insights into processes affecting neuronal communication. PMID- 27559173 TI - beta-Catenin Is Required for Endothelial Cyp1b1 Regulation Influencing Metabolic Barrier Function. AB - The canonical Wnt/beta-catenin signaling pathway is crucial for blood-brain barrier (BBB) formation in brain endothelial cells. Although glucose transporter 1, claudin-3, and plasmalemma vesicular-associated protein have been identified as Wnt/beta-catenin targets in brain endothelial cells, further downstream targets relevant to BBB formation and function are incompletely explored. By Affymetrix expression analysis, we show that the cytochrome P450 enzyme Cyp1b1 was significantly decreased in beta-catenin-deficient mouse endothelial cells, whereas its close homolog Cyp1a1 was upregulated in an aryl hydrocarbon receptor dependent manner, hence indicating that beta-catenin is indispensable for Cyp1b1 but not for Cyp1a1 expression. Functionally, Cyp1b1 could generate retinoic acid from retinol leading to cell-autonomous induction of the barrier-related ATP binding cassette transporter P-glycoprotein. Cyp1b1 could also generate 20 hydroxyeicosatetraenoic acid from arachidonic acid, decreasing endothelial barrier function in vitro In mice in vivo pharmacological inhibition of Cyp1b1 increased BBB permeability for small molecular tracers, and Cyp1b1 was downregulated in glioma vessels in which BBB function is lost. Hence, we propose Cyp1b1 as a target of beta-catenin indirectly influencing BBB properties via its metabolic activity, and as a potential target for modulating barrier function in endothelial cells. SIGNIFICANCE STATEMENT: Wnt/beta-catenin signaling is crucial for blood-brain barrier (BBB) development and maintenance; however, its role in regulating metabolic characteristics of endothelial cells is unclear. We provide evidence that beta-catenin influences endothelial metabolism by transcriptionally regulating the cytochrome P450 enzyme Cyp1b1 Furthermore, expression of its close homolog Cyp1a1 was inhibited by beta-catenin. Functionally, Cyp1b1 generated retinoic acid as well as 20-hydroxyeicosatetraenoic acid that regulated P glycoprotein and junction proteins, respectively, thereby modulating BBB properties. Inhibition of Cyp1b1 in vivo increased BBB permeability being in line with its downregulation in glioma endothelia, potentially implicating Cyp1b1 in other brain pathologies. In conclusion, Wnt/beta-catenin signaling regulates endothelial metabolic barrier function through Cyp1b1 transcription. PMID- 27559172 TI - P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus. AB - P2X4 receptors are ATP-gated cation channels that are widely expressed in the nervous system. To identify P2X4 receptor-expressing cells, we generated BAC transgenic mice expressing tdTomato under the control of the P2X4 receptor gene (P2rx4). We found sparse populations of tdTomato-positive neurons in most brain areas with patterns that matched P2X4 mRNA distribution. tdTomato expression within microglia was low but was increased by an experimental manipulation that triggered microglial activation. We found surprisingly high tdTomato expression in the hypothalamic arcuate nucleus (Arc) (i.e., within parts of the neural circuitry controlling feeding). Immunohistochemistry and genetic crosses of P2rx4 tdTomato mice with cell-specific GFP reporter lines showed that the tdTomato expressing cells were mainly AgRP-NPY neurons and tanycytes. There was no electrophysiological evidence for functional expression of P2X4 receptors on AgRP NPY neuron somata, but instead, we found clear evidence for functional presynaptic P2X4 receptor-mediated responses in terminals of AgRP-NPY neurons onto two of their postsynaptic targets (Arc POMC and paraventricular nucleus neurons), where ATP dramatically facilitated GABA release. The presynaptic responses onto POMC neurons, and the expression of tdTomato in AgRP-NPY neurons and tanycytes, were significantly decreased by food deprivation in male mice in a manner that was partially reversed by the satiety-related peptide leptin. Overall, we provide well-characterized tdTomato reporter mice to study P2X4 expressing cells in the brain, new insights on feeding-related regulation of presynaptic P2X4 receptor responses, and the rationale to explore extracellular ATP signaling in the control of feeding behaviors. SIGNIFICANCE STATEMENT: Cells expressing ATP-gated P2X4 receptors have proven problematic to identify and study in brain slice preparations because P2X4 expression is sparse. To address this limitation, we generated and characterized BAC transgenic P2rx4 tdTomato reporter mice. We report the distribution of tdTomato-expressing cells throughout the brain and particularly strong expression in the hypothalamic arcuate nucleus. Together, our studies provide a new, well-characterized tool with which to study P2X4 receptor-expressing cells. The electrophysiological studies enabled by this mouse suggest previously unanticipated roles for ATP and P2X4 receptors in the neural circuitry controlling feeding. PMID- 27559174 TI - Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory. AB - Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. SIGNIFICANCE STATEMENT: Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The phosphodiesterase 4 (PDE4) family coordinates the degradation of cAMP, leading to the local attenuation of cAMP-dependent signaling pathways. Sleep deprivation leads to increased hippocampal expression of the PDE4A5 isoform. Here, we explored whether PDE4A5 overexpression mimics behavioral and synaptic plasticity phenotypes associated with sleep deprivation. Viral expression of PDE4A5 in hippocampal neurons impairs long-term potentiation and attenuates the formation of hippocampus-dependent long term memories. Our findings suggest that PDE4A5 is a molecular constraint on cognitive processes and may contribute to the development of novel therapeutic approaches to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. PMID- 27559175 TI - Adult Neurogenesis Leads to the Functional Reconstruction of a Telencephalic Neural Circuit. AB - Seasonally breeding songbirds exhibit pronounced annual changes in song behavior, and in the morphology and physiology of the telencephalic neural circuit underlying production of learned song. Each breeding season, new adult-born neurons are added to the pallial nucleus HVC in response to seasonal changes in steroid hormone levels, and send long axonal projections to their target nucleus, the robust nucleus of the arcopallium (RA). We investigated the role that adult neurogenesis plays in the seasonal reconstruction of this circuit. We labeled newborn HVC neurons with BrdU, and RA-projecting HVC neurons (HVCRA) with retrograde tracer injected in RA of adult male white-crowned sparrows (Zonotrichia leucophrys gambelii) in breeding or nonbreeding conditions. We found that there were many more HVCRA neurons in breeding than nonbreeding birds. Furthermore, we observed that more newborn HVC neurons were back-filled by the tracer in breeding animals. Behaviorally, song structure degraded as the HVC-RA circuit degenerated, and recovered as the circuit regenerated, in close correlation with the number of new HVCRA neurons. These results support the hypothesis that the HVC-RA circuit degenerates in nonbreeding birds, and that newborn neurons reconstruct the circuit in breeding birds, leading to functional recovery of song behavior. SIGNIFICANCE STATEMENT: We investigated the role that adult neurogenesis plays in the seasonal reconstruction of a telencephalic neural circuit that controls song behavior in white-crowned sparrows. We showed that nonbreeding birds had a 36%-49% reduction in the number of projection neurons compared with breeding birds, and the regeneration of the circuit in the breeding season is due to the integration of adult-born projection neurons. Additionally, song structure degraded as the circuit degenerated and recovered as the circuit regenerated, in close correlation with new projection neuron number. This study demonstrates that steroid hormones can help reestablish functional neuronal circuits following degeneration in the adult brain and shows non-injury-induced degeneration and reconstruction of a neural circuit critical for producing a learned behavior. PMID- 27559177 TI - Neurons in Striate Cortex Signal Disparity in Half-Matched Random-Dot Stereograms. AB - Human stereopsis can operate in dense "cyclopean" images containing no monocular objects. This is believed to depend on the computation of binocular correlation by neurons in primary visual cortex (V1). The observation that humans perceive depth in half-matched random-dot stereograms, although these stimuli have no net correlation, has led to the proposition that human depth perception in these stimuli depends on a distinct "matching" computation possibly performed in extrastriate cortex. However, recording from disparity-selective neurons in V1 of fixating monkeys, we found that they are in fact able to signal disparity in half matched stimuli. We present a simple model that explains these results. This reinstates the view that disparity-selective neurons in V1 provide the initial substrate for perception in dense cyclopean stimuli, and strongly suggests that separate correlation and matching computations are not necessary to explain existing data on mixed correlation stereograms. SIGNIFICANCE STATEMENT: The initial step in stereoscopic 3D vision is generally thought to be a correlation based computation that takes place in striate cortex. Recent research has argued that there must be an additional matching computation involved in extracting stereoscopic depth in random-dot stereograms. This is based on the observation that humans can perceive depth in stimuli with a mean binocular correlation of zero (where a correlation-based mechanism should not signal depth). We show that correlation-based cells in striate cortex do in fact signal depth here because they convert fluctuations in the correlation level into a mean change in the firing rate. Our results reinstate the view that these cells provide a sufficient substrate for the perception of stereoscopic depth. PMID- 27559176 TI - Distinct Calcium Sources Support Multiple Modes of Synaptic Release from Cranial Sensory Afferents. AB - Most craniosensory afferents have unmyelinated axons expressing TRP Vanilloid 1 (TRPV1) receptors in synaptic terminals at the solitary tract nucleus (NTS). Neurotransmission from these synapses is characterized by substantial asynchronous EPSCs following action potential-synched EPSCs and high spontaneous rates that are thermally sensitive. The present studies blocked voltage-activated calcium channels (CaV) using the nonselective CaV blocker Cd(2+) or the specific N-type blocker omega-conotoxin GVIA to examine the calcium dependence of the synchronous, asynchronous, spontaneous, and thermally gated modes of release. In rat brainstem slices containing caudal NTS, shocks to the solitary tract (ST) triggered synchronous ST-EPSCs and trailing asynchronous EPSCs. Cd(2+) or GVIA efficiently reduced both synchronous and asynchronous EPSCs without altering spontaneous or thermal-evoked transmission. Activation of TRPV1 with either the selective agonist resiniferatoxin (150 pm) or temperature augmented basal sEPSC rates but failed to alter the synchronous or asynchronous modes of release. These data indicate that calcium sourced through TRPV1 has no access to the synchronous or asynchronous release mechanism(s) and conversely that CaV-sourced calcium does not interact with the thermally evoked mode of release. Buffering intracellular calcium with EGTA-AM or BAPTA-AM reduced asynchronous EPSC rates earlier and to a greater extent than synchronous ST-EPSC amplitudes without altering sEPSCs or thermal sensitivity. Buffering therefore distinguishes asynchronous vesicles as possessing a highly sensitive calcium sensor located perhaps more distant from CaV than synchronous vesicles or thermally evoked vesicles from TRPV1. Together, our findings suggest separate mechanisms of release for spontaneous, asynchronous and synchronous vesicles that likely reside in unique, spatially separated vesicle domains. SIGNIFICANCE STATEMENT: Most craniosensory fibers release glutamate using calcium entry from two sources: CaVs and TRPV1. We demonstrate that calcium segregation distinguishes three vesicle release mechanisms. Most surprisingly, asynchronous release is associated with CaV and not TRPV1 calcium entry. This reveals that asynchronous release is an additional and separate phenotypic marker of unmyelinated afferents rather than operated by TRPV1. The functional independence of the two calcium sources expands the regulatory repertoire of transmission and imbues these inputs with additional modulation targets for synaptic release not present at conventional CaV synapses. Peptides and lipid mediators may target one or both of these calcium sources at afferent terminals within the solitary tract nucleus to independently modify release from distinct, functionally segregated vesicle pools. PMID- 27559178 TI - The Nucleus Reuniens of the Midline Thalamus Gates Prefrontal-Hippocampal Modulation of Ventral Tegmental Area Dopamine Neuron Activity. AB - The circuitry mediating top-down control of dopamine (DA) neurons in the ventral tegmental area (VTA) is exceedingly complex. Characterizing these networks will be critical to our understanding of fundamental behaviors, such as motivation and reward processing, as well as several disease states. Previous work suggests that the medial prefrontal cortex (mPFC) exerts a profound influence on VTA DA neuron firing. Recently, our group reported that inhibition of the infralimbic subdivision of the medial prefrontal cortex (ilPFC) increases the proportion of VTA DA neurons that are spontaneously active (i.e., "population activity") and that this effect depends on activity in the ventral subiculum of the hippocampus (vSub). However, there is no direct projection from the mPFC to the vSub. Anatomical evidence suggests that communication between the two structures is mediated by the nucleus reuniens of the midline thalamus (RE). Here, we used in vivo electrophysiological and behavioral approaches in rats to explore the role of the RE in the circuitry governing VTA DA neuron firing. We show that pharmacological stimulation of the RE enhances VTA DA neuron population activity and amphetamine-induced hyperlocomotion, a behavioral indicator of an over responsive DA system. Furthermore, the effect of RE stimulation on population activity is prevented if vSub is also inhibited. Finally, pharmacological inhibition of ilPFC enhances VTA DA neuron population activity, but this effect does not occur if RE is also inhibited. These findings suggest that disruption of ilPFC-RE-vSub communication could lead to a dysregulated, hyperdopaminergic state, and may play a role in psychiatric disorders. SIGNIFICANCE STATEMENT: Dopamine (DA) neurons in the ventral tegmental area (VTA) are involved in a variety of fundamental brain functions. To understand the neurobiological basis for these functions it is essential to identify regions controlling DA neuron activity. The medial prefrontal cortex (mPFC) is emerging as a key regulator of DA neuron activity, but the circuitry by which it exerts its influence remains poorly described. Here, we show that the nucleus reuniens of the midline thalamus gates mPFC control of VTA DA neuron firing by the hippocampus. These data identify a unique role for this corticothalamic-hippocampal circuit, and suggest that dysfunction in these regions likely influences the pathophysiology of psychiatric disorders. PMID- 27559179 TI - Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals. AB - In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ~8-12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. SIGNIFICANCE STATEMENT: The timing patterns of action potentials, or spikes, play important roles in representing information in the nervous system. However, how these temporal patterns are recognized by downstream neurons is not well understood. Here we use the electrosensory system of mormyrid weakly electric fish to investigate how a population of neurons with diverse temporal filtering properties encodes behaviorally relevant input timing patterns, and how this relates to behavioral sensitivity. We show that fish are behaviorally sensitive to millisecond variations in natural, temporally patterned communication signals, and that the responses of individual midbrain neurons are also sensitive to variation in these patterns. In fact, the output of single neurons contains enough information to discriminate stereotyped communication signals produced by different individuals. PMID- 27559180 TI - Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions. AB - Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ~90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. SIGNIFICANCE STATEMENT: Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called "phase amplitude coupling." PMID- 27559183 TI - Partially Filled Vials and Syringes in Sharps Containers Are a Key Source of Drugs for Diversion: ISMP Targeted Medication Safety Best Practice #9 Are Patients Who Are Allergic to Antibiotics at Risk for Reactions to Vaccine Ingredients? AB - These medication errors have occurred in health care facilities at least once. They will happen again-perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site (www.ismp.org), by calling 800-FAIL-SAFE, or via e mail at ismpinfo@ismp.org. ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications. PMID- 27559181 TI - Role of genetic susceptibility variants in predicting clinical course in multiple sclerosis: a cohort study. AB - BACKGROUND: The genetic drivers of multiple sclerosis (MS) clinical course are essentially unknown with limited data arising from severity and clinical phenotype analyses in genome-wide association studies. METHODS: Prospective cohort study of 127 first demyelinating events with genotype data, where 116 MS risk-associated single nucleotide polymorphisms (SNPs) were assessed as predictors of conversion to MS, relapse and annualised disability progression (Expanded Disability Status Scale, EDSS) up to 5-year review (DeltaEDSS). Survival analysis was used to test for predictors of MS and relapse, and linear regression for disability progression. The top 7 SNPs predicting MS/relapse and disability progression were evaluated as a cumulative genetic risk score (CGRS). RESULTS: We identified 2 non-human leucocyte antigen (HLA; rs12599600 and rs1021156) and 1 HLA (rs9266773) SNP predicting both MS and relapse risk. Additionally, 3 non-HLA SNPs predicted only conversion to MS; 1 HLA and 2 non-HLA SNPs predicted only relapse; and 7 non-HLA SNPs predicted DeltaEDSS. The CGRS significantly predicted MS and relapse in a significant, dose-dependent manner: those having >=5 risk genotypes had a 6-fold greater risk of converting to MS and relapse compared with those with <=2. The CGRS for DeltaEDSS was also significant: those carrying >=6 risk genotypes progressed at 0.48 EDSS points per year faster compared with those with <=2, and the CGRS model explained 32% of the variance in disability in this study cohort. CONCLUSIONS: These data strongly suggest that MS genetic risk variants significantly influence MS clinical course and that this effect is polygenic. PMID- 27559182 TI - Outcome Assessment of Critical Care Pharmacist Services. PMID- 27559184 TI - Delayed Anaphylaxis with Methimazole: Nicolau Syndrome After Oxytocin Intramuscular Administration Anastrazole-Induced Autoimmune Hepatitis Amoxicillin and Cephalexin-Induced Eosinophilic Colitis Docetaxel-Induced Supravenous Erythematous Eruption. AB - The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID- 27559185 TI - Alectinib, Ceritinib, Elotuzumab, and Venetoclax. AB - The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. PMID- 27559186 TI - Minocycline: Rheumatoid Arthritis. AB - This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu. PMID- 27559187 TI - Significant Published Articles for Pharmacy Nutrition Support Practice in 2014 and 2015. AB - PURPOSE: To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature. METHODS: Several experienced board certified clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2014 and 2015 that they considered to be important to their practice. Only those articles available in print format were considered for potential inclusion. Articles available only in preprint electronic format were not evaluated. The citation list was compiled into a single spreadsheet where the author participants were asked to ascertain whether they considered the paper important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important. RESULTS: A total of 108 articles were identified; 36 of which were considered to be of high importance. An important guideline article published in early 2016, but not ranked, was also included. The top-ranked articles from the primary literature were reviewed. CONCLUSION: It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these articles. PMID- 27559188 TI - Enzyme Replacement or Substrate Reduction? A Review of Gaucher Disease Treatment Options. AB - BACKGROUND: Gaucher disease is a rare lysosomal storage disease resulting from a deficiency or reduced activity in the acid beta-glucocosidase enzyme. Only 1 treatment option was available for 15 years, but several new treatment options have come to market since 2003. OBJECTIVE: The article will detail the pathophysiology and review current therapies in the literature for all 3 major clinical types of Gaucher disease, with a focus on considerations for selecting therapy in type 1 disease. METHODS: Extracted and summarized applicable studies and reviews from Cochrane Review, ClinicalTrials.gov, CINAHL, IPA, and PubMed. RESULTS: Enzyme replacement therapy is preferred for the management of Gaucher disease. Current literature does not favor any enzyme replacement product over another. However, velaglucerase alfa and taliglucerase alfa theoretically have a lower risk of immunogenicity reactions compared with imiglucerase. Alternative treatments for type 1 disease include substrate reduction therapy; however, these treatments require evaluation of patient-specific variables (eg, genotype evaluation, renal function) and consideration of adverse effect and dosing profiles. Evaluation of current literature found no substrate reduction therapy is preferred over another. There are no approved therapies for type 2 and type 3 disease, but enzyme replacement therapy may be used with limited efficacy for symptom management. CONCLUSION: Enzyme replacement therapy is preferred for treating type 1 Gaucher disease and substrate replacement therapy may be considered in patients who do not tolerate or cannot receive enzyme replacement therapy. PMID- 27559189 TI - Antithrombotic Usage Patterns in the Era of New Oral Anticoagulant Options for Atrial Fibrillation. AB - BACKGROUND: Appropriate treatment reduces the risk of stroke in patients with atrial fibrillation (AF). Despite the known benefits of warfarin, anticoagulation prescribing rates remain inadequate in high-risk patients. Over the last 6 years, 4 novel oral anticoagulants have been approved for use for stroke prophylaxis in non-valvular AF (NVAF), which may allow prescribers to tailor therapy for each NVAF patient. OBJECTIVE: The goal of this investigation was to determine the effect of dabigatran and rivaroxaban availability on the rate of anticoagulant prescribing at hospital discharge in patients with a principal diagnosis of NVAF. METHODS: A retrospective chart review of adult patients presenting with NVAF (CHADS2 score >=2) was conducted using a historical control group of patients from 2009 compared to patients admitted in 2012 following formulary availability of dabigatran and rivaroxaban. In addition to antithrombotic therapy prescribed, subsequent hospitalizations during a 1-year period were reviewed for major bleeding and stroke events. RESULTS: Two hundred patients were enrolled in the study. The rate of anticoagulant prescribing in the 2009 and 2012 groups was 68.3% and 77.1%, respectively (p = .16). Of the patients in the 2012 group prescribed an anticoagulant, 58 (64%) received warfarin, 26 (28%) received dabigatran, and 7 (8%) received rivaroxaban. One patient (1.2%) in the 2009 group and 4 patients (4.4%) in the 2012 group had a major bleed (p = .4). CONCLUSION: There was no statistical difference in the rate of anticoagulant prescribing between the 2 groups. Despite the availability of additional anticoagulant options, the rate of prescribing remains suboptimal in this high-risk population. PMID- 27559190 TI - Utilization of Pharmaceutical Patient and Prescription Assistance Programs via a Pharmacy Department Patient Assistance Program for Indigent Cancer Patients. AB - BACKGROUND: With the advances in cancer treatments, mortality rates in the United States have been consistently falling but they are accompanied by substantial increases in the cost of cancer care. Patient and prescription assistance programs (PPAPs) are offered by pharmaceutical manufacturers to provide free medications to medically indigent patients. To assist the Cancer Care Center (CCC) at Nassau University Medical Center (NUMC) with drug costs for chemotherapies, the pharmacy department uses a patient assistance program (PAP) to obtain medications from the drug companies at no cost. PURPOSE: This study evaluates the impact of the PAP at a public hospital from which indigent cancer patients obtain assistance for chemotherapy. METHODS: We followed all patients requiring assistance with chemotherapy who enrolled in the PAP from January 1, 2011 through December 31, 2012. Medications included both oral and parenteral chemotherapy drugs and antiemetics used in the outpatient clinic setting. RESULTS: The program served 347 patients in 2011 and 579 patients in 2012. The total number of visits in the clinic over 24 months was 9,405. The total cost savings of the medications was $1,066,000 in 2011 and $1,715,538 in 2012. CONCLUSIONS: A pharmacy-based PAP to procure free medications from PPAPs for cancer patients has helped to defray the expense of providing care at NUMC, increased patients' compliance with chemo protocols, and allowed many patients to receive the treatment they otherwise would not be able to afford. The combination of PPAPs and PAP provides a safety net to ensure that indigent cancer patients receive needed prescription medications in the outpatient clinic setting. PMID- 27559191 TI - Implementing the Use of Pharmacist Progress Notes in a Surgical ICU. AB - BACKGROUND: Critical care pharmacists are established and valuable members of the critical care team, however there is rarely written evidence of their daily involvement in the patient's electronic medical record (EMR). Documentation in the EMR has the advantage of ensuring a seamless pass-off and provides an opportunity to capture the pharmacist's cognitive and clinical impact in a way that traditional systems of tracking "interventions" fail to do. We investigated implementation of pharmacist progress notes in a surgical intensive care unit (ICU) and their utility in measuring pharmacist activity. METHODS: Daily pharmacist progress notes written in a surgical ICU over a period of 2 months were reviewed. Each pharmacist action identified through progress note review was quantified and scored by an independent reviewer using a newly developed scoring system, the clinical impact score (CIS). This was developed as a way to quantify pharmacist actions and to classify those actions by clinical impact. RESULTS: Four hundred sixty-two daily pharmacist progress notes were reviewed over a 2 month period. There were 1,055 actions identified that resulted in a therapy change. Four of these actions resulted in the potential avoidance of a sentinel event. Of patients with at least 5 progress notes (n = 44), the majority of pharmacist actions occurred on ICU day 1. CONCLUSION: The results of this descriptive study demonstrate that the implementation of daily pharmacist progress notes is feasible in an advanced practice setting, and the pharmacist's contribution to patient care may be obtained through review of this documentation in the patient's medical record. The critical care pharmacist's daily involvement in patient care most commonly results in optimization of pharmacotherapy and avoidance of drug misadventure. PMID- 27559192 TI - Sugammadex. AB - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The July 2016 monograph topics are pimavanserin, venetoclax, defibrotide, lifitegrast ophthalmic solution 5%, and atezolizumab. The Safety MUE is on pimavanserin. PMID- 27559193 TI - Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals. AB - This monthly feature will help readers keep current on new drug, new indications, dosage forms and safety-related changes in labeling or use. Efforts have been made to assure the accuracy of this information; however, if there are any questions, please let us know at jgeneral@ku.edu. For this combined issue, a 2 month period is covered (April 16, 2016 through June 16, 2016). PMID- 27559194 TI - Big Data: Implications for Health System Pharmacy. AB - Big Data refers to datasets that are so large and complex that traditional methods and hardware for collecting, sharing, and analyzing them are not possible. Big Data that is accurate leads to more confident decision making, improved operational efficiency, and reduced costs. The rapid growth of health care information results in Big Data around health services, treatments, and outcomes, and Big Data can be used to analyze the benefit of health system pharmacy services. The goal of this article is to provide a perspective on how Big Data can be applied to health system pharmacy. It will define Big Data, describe the impact of Big Data on population health, review specific implications of Big Data in health system pharmacy, and describe an approach for pharmacy leaders to effectively use Big Data. A few strategies involved in managing Big Data in health system pharmacy include identifying potential opportunities for Big Data, prioritizing those opportunities, protecting privacy concerns, promoting data transparency, and communicating outcomes. As health care information expands in its content and becomes more integrated, Big Data can enhance the development of patient-centered pharmacy services. PMID- 27559195 TI - Clinical and Business Intelligence: Why It's Important to Your Pharmacy. AB - According to the Healthcare Information Management and Systems Society, "Clinical & Business Intelligence (C&BI) is the use and analysis of data captured in the healthcare setting to directly inform decision-making" (http://www.himss.org/library/clinical-business-intelligence). Some say that it is the right information given to the right person at the right time in the right way. No matter how you define it, the fact remains that timely access, synthesis, and visualization of clinical data have become key to how health professionals make patient care decisions and improve care delivery. PMID- 27559196 TI - Metamorphic Testing for Cybersecurity. AB - Testing is a major approach for the detection of software defects, including vulnerabilities in security features. This article introduces metamorphic testing (MT), a relatively new testing method, and discusses how the new perspective of MT can help to conduct negative testing as well as to alleviate the oracle problem in the testing of security-related functionality and behavior. As demonstrated by the effectiveness of MT in detecting previously unknown bugs in real-world critical applications such as compilers and code obfuscators, we conclude that software testing of security-related features should be conducted from diverse perspectives in order to achieve greater cybersecurity. PMID- 27559197 TI - Lung Transplantation and Survival in Children with Cystic Fibrosis. AB - BACKGROUND: The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain. METHODS: We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis. RESULTS: A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection was associated with a trend toward decreased survival, regardless of whether the patient underwent transplantation. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 283 patients had a significant risk of harm, 102 patients had an insignificant benefit, and 124 patients had an insignificant risk of harm associated with lung transplantation. CONCLUSIONS: Our analyses estimated clearly improved survival for only 5 of 514 patients on the waiting list for lung transplantation. Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality-of-life benefit from lung transplantation. PMID- 27559199 TI - Editorial. PMID- 27559198 TI - Evolution of Welding-Fume Aerosols with Time and Distance from the Source: A study was conducted on the spatiotemporal variability in welding-fume concentrations for the characterization of first- and second-hand exposure to welding fumes. AB - Gas metal arc welding fumes were generated from mild-steel plates and measured near the arc (30 cm), representing first-hand exposure of the welder, and farther away from the source (200 cm), representing second-hand exposure of adjacent workers. Measurements were taken during 1-min welding runs and at subsequent 5 min intervals after the welding process was stopped. Number size distributions were measured in real time. Particle mass distributions were measured using a micro-orifice uniform deposition impactor, and total mass concentrations were measured with polytetrafluorothylene filters. Membrane filters were used for collecting morphology samples for electron microscopy. Average mass concentrations measured near the arc were 45 mg/m3 and 9 mg/m3 at the farther distance. The discrepancy in concentrations at the two distances was attributed to the presence of spatter particles, which were observed only in the morphology samples near the source. As fumes aged over time, mass concentrations at the farther distance decreased by 31% (6.2 mg/m3) after 5 min and an additional 13% (5.4 mg/m3) after 10 min. Particle number and mass distributions during active welding were similar at both distances, indicating similar exposure patterns for welders and adjacent workers. Exceptions were recorded for particles smaller than 50 nm and larger than 3 MUm, where concentrations were higher near the arc, indicating higher exposures of welders. These results were confirmed by microscopy analysis. As residence time increased, number concentrations decreased dramatically. In terms of particle number concentrations, second-hand exposures to welding fumes during active welding may be as high as first-hand exposures. PMID- 27559200 TI - The State of Regulation in England: From the General Social Care Council to the Health and Care Professions Council. AB - In this paper, we analyse the way in which social work, as a profession, has coped with and responded to the various forms of regulation to which it has been subject in England. First, we briefly detail the rise of external regulation of the professions, discussing both the rationale for, and criticisms of, such developments. Second, we take a closer look at developments within social work and the operation of the General Social Care Council (GSCC)'s conduct proceedings from its inception in 2001 until its dissolution in 2012. Third, we focus on the Health and Care Professions Council (HCPC) and consider how it has begun its regulation of social workers since it took on this responsibility from August 2012. We conclude by outlining some of the concerns we have as well as discussing reasons as to why we feel this area of work needs to be explored further. PMID- 27559201 TI - Identification with the SocialWork Profession: The Impact of Education. AB - The aim of this study is to examine how education affects students' identification with the social work profession. In particular, we examine the impact of students' experiences of their interactions with teachers, peers and supervisors at placement. A longitudinal design is applied. Data were collected from students during their first and third (final) year in social work education from seven universities and university colleges in Norway, representing a sample (panel) of 390 students. To evaluate the degree of students' identification with the profession, comparisons with student nurses are conducted. The analyses indicate (i) that students' dedication to and identification with the social work profession are largely established at a very early stage of education and (ii) that education has a positive impact on students' identification with the social work profession. At the end of their social work education, students who experience support and feedback from teachers and have confidence in their supervisors' competence express a higher degree of identification with the social work profession. PMID- 27559202 TI - Social Work Field Training for the Community: A Student Self-Directed Approach in the Environmental Domain in Jordan. AB - This article outlines innovative field training methods that foster the abilities of undergraduate social work students so that they are able to empower the local community and raise awareness of environmental issues. In this study, students were engaged in a local community assessment that sought to understand their views on environmental and community impacts of the Synchrotron-Light for Experimental Science and Applications in the Middle East (SESAME) Project on the lives of the host village's residents. A students' self-directed approach was applied for the fieldwork out of which interventions were developed ( Garrison, 1997). Quantitative data were gathered by eighteen students through a survey of 361 questionnaires targeting Allan society. In addition to students' field notes, pre and post focus groups were used to collect qualitative information. Study findings highlighted the effectiveness of students' self-directed projects in cultivating culturally competent practices; ensuring sustainable development; and providing evidence-based knowledge on social work practice involving environmental issues. PMID- 27559204 TI - Towards a Human Rights Culture in Social Work Education. AB - A human rights perspective must be embedded in the institutions, organisations or agencies where social work students find themselves. This paper will focus on one particular strategy that could be helpful to the process of solidifying a commitment to human rights for our students. Using a pedagogical tool from a school of social work in the USA originally developed to combat the social injustice of racism, the example transcends the academic institution and offers a solid link in connecting human rights, social justice and social work. Using the construct of critical realism, we argue that, for social work programmes to take steps towards an explicit commitment to human rights, not only must human rights be infused throughout the curriculum, but educators must provide opportunities for making more overt the links between human rights principles, social justice and social work. By addressing behaviours, tendencies and attitudes, students then acquire not only the skills and deeper understanding, but they internalise the motivation and commitment to broaden their human rights frame. In the process of developing a more firm commitment to human rights, we must not be limited to the walls of the academy, but rather extend beyond to our field agencies, organisations and communities. PMID- 27559203 TI - 'Introducing Michael Gove to Loic Wacquant': Why Social Work Needs Critical Sociology. AB - In 2013, Michael Gove, then Secretary of State for Education and Health in the UK coalition government, criticised social workers for laying insufficient emphasis on the 'agency' of individuals and for being too preoccupied with social and economic inequalities. Such a perspective, which is not unique to Gove, needs to be countered by reaffirming the significance of an expansively critical sociology for social work. In this context, the thematic concerns of the French theorist, Loic Wacquant, illuminates key aspects of social work engagement with clients which Gove and his ideological associates appear intent on ignoring. The issues raised have significant political resonances given the pending UK General Election taking place in May 2015. PMID- 27559205 TI - Transforming Practice with Older People through an Ethic of Care. AB - This article explores the relevance of deliberative practices framed by feminist care ethics to social work practice with older people. It draws on two connected projects which brought together older people: practitioners and academics. The first was a participatory research project in which the significance of care to well-being in old age emerged. The second was a knowledge exchange project which generated learning resources for social care practice based on the research findings of the first project. Here we analyse selected transcripts of recordings from meetings of both projects to consider the ways that discussions about lived experiences and everyday lives demonstrate care through this dialogue. Using this analysis, we propose that care ethics can be useful in transforming relationships between older people and those working with them through the creation of hybrid spaces in which 'care-full deliberation' can happen. We argue that such reflective spaces can enable transformative dialogue about care and its importance to older people and offer a counterbalance to the procedurally driven environments in which much social work practice takes place and can support practice more attuned to the circumstances and concerns of older people. PMID- 27559206 TI - Exploring Demand and Provision in English Child Protection Services. AB - This paper presents the results of an exploratory study linking the national data sets for all children in need and child protection services in England. The study was informed by an emerging literature on systems thinking in public services, and aimed to examine variations and patterns of response in local authorities to demand for child welfare services in their area. One hundred and fifty-two local authority census returns and other statistical indicators covering up to a thirteen-year period were combined into a single data-set. Statistical analysis was undertaken to explore the characteristics of demand, workload and workforce, trends over time and variations between local authorities. The results showed that the overall system has become increasingly geared towards protective interventions, especially since the Baby P scandal of 2008. Deprivation levels continue to be the key driver of referrals and other categories of demand, and are strongly associated with variations in service response, particularly in the initial stages of referral and assessment. Implications are considered for the current organisation of child welfare services in light of recent reviews and reforms. PMID- 27559207 TI - Family Group Conferences and Cultural Competence in Social Work. AB - Family Group Conferences (FGCs) as a method of preventive work came into being over two decades ago. The FGC approach arose from a minority cultural perspective and the rising numbers of Maori children in state care in New Zealand. Two decades after the Family Rights Group first championed FGC in the UK, it is a great concern that we know little or nothing about how such an approach is being utilised with culturally diverse families in the UK. This paper draws upon an empirical study carried out in London to ascertain the views and experiences of social and community work FGC coordinators and managers, located in statutory and non-government organisations, who employed the FGC approach with culturally diverse families. Findings from this study are discussed in the context of extant research literature into the nature and extent of involvement of black and minority ethnic (BME) families with child welfare services across the globe. Moreover, given the inherent emphasis on the foundational 'cultural framework' of the FGC approach, the paper makes an important contribution to the literature on cultural competence within social work through the practice of FGC. PMID- 27559208 TI - An Evidence-Based, Pre-Birth Assessment Pathway for Vulnerable Pregnant Women. AB - The developmental needs of infants during the first year of life have been emphasised by recent research from a variety of sources highlighting the crucial role that early parent-infant interaction plays. Infants identified as being at significant risk of maltreatment need adequate protection within a time frame consistent with their developmental needs. This briefing paper describes a new care pathway established within a UK-based social care team, which aims to provide early identification, intensive support, timely assessment and decision making for a group of highly vulnerable, pregnant women, their partners and their infants. The pathway of care is described and a case study is presented to illustrate this care pathway. A mother is referred at eighteen weeks of pregnancy and supported post birth for six months. The combination of supporting structured professional judgement by the inclusion of standardised tools and training in a programme specifically developed for high-risk families suggests that this pre birth risk-assessment process warrants further evaluation. PMID- 27559209 TI - Family Finding and Matching in Adoption: What Helps to Make a Good Match? AB - This study compared the effectiveness and outcomes of different family finding methods in adoption in England, over-selecting harder to place children. The case files of 149 children with adoption recommendations in ten local authorities were reviewed and a sub-sample of sixty-seven cases were followed in real time, through interviews with professionals and families until six months after adoptive placement. Most matches were of good quality, but 14 per cent were fair and 13 per cent poor, involving serious compromises on matching requirements or adopters' preferences. There were more poor matches when in-house placements were made or children's difficulties were underplayed with new parents and, necessarily, more compromises were made when matching children with significant health or developmental needs. More good quality matches were made when case responsibility was transferred early to the adoption team. Poorer quality matches were related to poorer outcomes six months after adoptive placement. To improve matching, searches for families need to be widened early to avoid delays and to maximise the pool of adopters. Formal processes to track and review the progress of adoptions for children with complex needs (including matching meetings) can help avoid delay and ensure that a group of professionals, rather than an individual professional, makes key decisions. PMID- 27559210 TI - Household Food Insecurity and Children's Behaviour Problems: New Evidence from a Trajectories-Based Study. AB - This study examined the association between household food insecurity (insufficient access to adequate and nutritious food) and trajectories of externalising and internalising behaviour problems in children from kindergarten to fifth grade using longitudinal data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), a nationally representative study in the USA. Household food insecurity was assessed using the eighteen-item standard food security scale, and children's behaviour problems were reported by teachers. Latent growth curve analysis was conducted on 7,348 children in the ECLS-K, separately for boys and girls. Following adjustment for an extensive array of confounding variables, results suggest that food insecurity generally was not associated with developmental change in children's behaviour problems. The impact of food insecurity on behaviour problems may be episodic or interact with certain developmental stages. PMID- 27559211 TI - Enacting Firm, Fair and Friendly Practice: A Model for Strengths-Based Child Protection Relationships? AB - Strengths-based solution-focused approaches are gaining ground in statutory child protection work, but few studies have asked front line practitioners how they navigate the complex worker-client relationships such approaches require. This paper describes one component of a mixed-methods study in a large Canadian statutory child protection agency in which 225 workers described how they applied the ideas of strengths-based practice in their daily work. Interviews with twenty four practitioners were analysed using an interpretive description approach. Only four interviewees appeared to successfully enact a version of strengths-based practice that closely mirrored those described by key strengths-based child protection theorists and was fully congruent with their mandated role. They described navigating a shifting balance of collaboration and authority in worker client relationships based on transparency, impartial judgement, attentiveness to the worker-client interaction and the value that clients were fellow human beings. Their accounts extend current conceptualisations of the worker-client relationship in strengths-based child protection work and are congruent with current understandings of effective mandated relationships. They provide what may be a useful model to help workers understand and navigate relationships in which they must reconcile their own authority and expertise with genuine support for the authority and expertise of their clients. PMID- 27559212 TI - Client Self-Management: Promoting Self-Help for Parents of Children in Foster Care. AB - Drawing upon Foucault's concepts of power, this article shows how a course given to parents whose children are in foster-care encourages a particular form of self management-most notably, that their internal dialogues must be altered so that the parents can view themselves as people in control of their behaviour who are in a position to choose new behaviour. The article is based on a qualitative study conducted in Norway and centres on the support and development of participants in the course. Study results show increased self-confidence and self respect in the participants, both as individuals and as parents. In addition, significant benefits were stated as finding that they could verbalise and describe difficult events and emotions, experiencing being 'normal' within a group and receiving feedback. From the perspective of child protective services, dialogue with parents is central, as it not only commits clients to specific behaviours, but-more importantly-commits them to a particular inner dialogue about parenthood. The course can be seen as a management tool in which the parent's 'self' becomes the central object, seeking to contradict the conventional conception of parents with children in foster-care as having nothing to contribute to their children's upbringing. PMID- 27559213 TI - Predictive Risk Modelling to Prevent Child Maltreatment and Other Adverse Outcomes for Service Users: Inside the 'Black Box' of Machine Learning. AB - Recent developments in digital technology have facilitated the recording and retrieval of administrative data from multiple sources about children and their families. Combined with new ways to mine such data using algorithms which can 'learn', it has been claimed that it is possible to develop tools that can predict which individual children within a population are most likely to be maltreated. The proposed benefit is that interventions can then be targeted to the most vulnerable children and their families to prevent maltreatment from occurring. As expertise in predictive modelling increases, the approach may also be applied in other areas of social work to predict and prevent adverse outcomes for vulnerable service users. In this article, a glimpse inside the 'black box' of predictive tools is provided to demonstrate how their development for use in social work may not be straightforward, given the nature of the data recorded about service users and service activity. The development of predictive risk modelling (PRM) in New Zealand is focused on as an example as it may be the first such tool to be applied as part of ongoing reforms to child protection services. PMID- 27559214 TI - Not All that Is Solid Melts into Air? Care-Experienced Young People, Friendship and Relationships in the 'Digital Age'. AB - The circumstances of those who are, or have been, in the care system may augment concern about their use of mobile phones and the internet, but little is specifically known about such use. Presenting findings from an exploratory study which investigated the experiences and views of six care leavers and four looked after children, this paper considers their social contact via mobile phones and the internet. Exploration of the study data is located alongside wider empirical findings around internet use and critical consideration of theoretical insights from the work of Bauman, Castells and LaMendola. Participants' reported use of digital media was not substantially different to that of their peer group: their core virtual networks had significant overlap with their core offline networks and social contact via digital media could provide welcome, if limited and individualised, social support. The most prominent difficulty arising from the use of these media was forms of verbal abuse by those known to the young people offline. While the centrality of digital technology within young people's lives influenced the way they communicated, underlying issues within their social relationships reflected greater similarity with a pre-digital age than has sometimes been suggested. PMID- 27559215 TI - 'I'm So Stressed!': A Longitudinal Model of Stress, Burnout and Engagement among Social Workers in Child Welfare Settings. AB - The well-documented day-to-day and long-term experiences of job stress and burnout among employees in child welfare organisations increasingly raise concerns among leaders, policy makers and scholars. Testing a theory-driven longitudinal model, this study seeks to advance understanding of the differential impact of job stressors (work-family conflict, role conflict and role ambiguity) and burnout (emotional exhaustion and depersonalisation) on employee disengagement (work withdrawal and exit-seeking behaviours). Data were collected at three six-month intervals from an availability sample of 362 front line social workers or social work supervisors who work in a large urban public child welfare organisation in the USA. The study's results yielded a good model fit (RMSEA = 0.06, CFI = 0.96, NFI = 0.94). Work-family conflict, role ambiguity and role conflict were found to impact work withdrawal and exit-seeking behaviours indirectly through burnout. The outcome variable, exit-seeking behaviours, was positively impacted by depersonalisation and work withdrawal at a statistically significant level. Overall, findings, at least in the US context, highlight the importance of further examining the development of job burnout among social workers and social work supervisors working in child welfare settings, as well as the utility of long-term administrative strategies to mitigate risks of burnout development and support engagement. PMID- 27559216 TI - Workplace Congruence and Occupational Outcomes among Social Service Workers. AB - Workplace expectations reflect an important consideration in employee experience. A higher prevalence of workplace congruence between worker and employer expectations has been associated with higher levels of productivity and overall workplace satisfaction across multiple occupational groups. Little research has investigated the relationship between workplace congruence and occupational health outcomes among social service workers. This study sought to better understand the extent to which occupational congruence contributes to occupational outcomes by surveying unionised social service workers (n = 674) employed with the Government of Alberta, Canada. Multiple regression analysis shows that greater congruence between workplace and worker expectations around workloads, workplace values and the quality of the work environment significantly: (i) decreases symptoms related to distress and secondary traumatic stress; (ii) decreases intentions to leave; and (iii) increases overall life satisfaction. The findings provide some evidence of areas within the workplace of large government run social welfare programmes that can be better aligned to worker expectations to improve occupational outcomes among social service workers. PMID- 27559217 TI - Hepatitis C and Social Work. AB - It is now a full decade since Paylor and Orgel (2004) called for social work to 'wake up' to hepatitis C (HCV). In that time, a small but significant body of social research has developed which has highlighted the far-reaching social consequences of living with HCV. Using this as a foundation, Paylor and Mack (2010) expanded arguments on the role of social work and identified specific areas where social work might become involved, arguing that the profession is uniquely placed and skilled, to respond and provide support. This article draws on qualitative in-depth interviews with twenty-one people who (had) lived with HCV in the UK, to strengthen and broaden the argument that social work and social care need to urgently take a bigger role in working with people with HCV, given the cross-cutting and wide range of issues that arise. This is the first study which uses participant data to argue for the need for social work involvement and in that it highlights a number of points in the experience where social work support is needed including pre and post diagnosis, whilst on treatment and after treatment. PMID- 27559218 TI - Moving Away from Social Work and Half Way Back Again: New Research on Skills in Probation. AB - Research on social work in the criminal justice system was well represented in the social work literature until the 1990s. Since then, changes in the organisation, training and research base of probation practice, particularly in England and Wales, have all contributed to a separation between probation research and the mainstream social work research literature. However, recent probation research, by focusing on individual practice skills and on the quality of relationships, is producing findings which resonate with traditional social work concerns. The study presented here, based on analysis of videotaped interviews between probation staff and the people they are supervising, shows what skills are used and the effects of skilled supervision. People supervised by more skilled staff were significantly less likely to be reconvicted over a two year follow-up, and the most effective supervisors combined good relationship skills with a range of 'structuring' or change-promoting skills. In effect, this can be regarded as a test of the impact of social work skills used by probation staff and suggests that a closer relationship between mainstream social work research and probation research could be productive for both. PMID- 27559219 TI - Editorial: Daring to Speak Out. PMID- 27559220 TI - Defensive Practice as 'Fear-Based' Practice: Social Work's Open Secret? AB - Defensive practice has received attention through the Munro review of child protection, which has identified that current organisational cultures increase the likelihood of defensive practice. Whilst the wider socio-political climate that gives rise to defensive practice has been explored within the literature, little attention has been paid to the everyday realities of defensive practice. This paper reports the findings of a study into final year social work students' attitudes towards defensive practice within social work. Three focus groups were completed with a total of ninety final-year students that collected qualitative and quantitative data using interactive software. This paper examines how participants perceived defensive practice, both in general and when faced with real-life vignettes. Participants distinguished between pro-active behaviour (sins of commission) and passive behaviour (sins of omission), generally regarding the latter as less serious because it was less tangible and easier to attribute to more positive motives. Whilst the literature identifies defensive practice as deliberate behaviour, the focus group discussions suggest that it is a subtler and less conscious process. Whilst there was there was a general consensus about the nature of defensive practice, there was considerable disagreement about specific vignettes and several competing explanations are explored. PMID- 27559221 TI - Social Work Home Visits to Children and Families in the UK: A Foucauldian Perspective. AB - The home visit is at the heart of social work practice with children and families; it is what children and families' social workers do more than any other single activity (except for recording), and it is through the home visit that assessments are made on a daily basis about risk, protection and welfare of children. And yet it is, more than any other activity, an example of what Pithouse has called an 'invisible trade': it happens behind closed doors, in the most secret and intimate spaces of family life. Drawing on conceptual tools associated with the work of Foucault, this article sets out to provide a critical, chronological review of research, policy and practice on home visiting. We aim to explain how and in what ways changing discourses have shaped the emergence, legitimacy, research and practice of the social work home visit to children and families at significant time periods and in a UK context. We end by highlighting the importance for the social work profession of engagement and critical reflection on the identified themes as part of their daily practice. PMID- 27559222 TI - The Voice of the Child in Social Work Assessments: Age-Appropriate Communication with Children. AB - This article describes a child-centred method for engaging with children involved in the child protection and welfare system. One of the primary arguments underpinning this research is that social workers need to be skilled communicators to engage with children about deeply personal and painful issues. There is a wide range of research that maintains play is the language of children and the most effective way to learn about children is through their play. Considering this, the overarching aim of this study was to investigate the role of play skills in supporting communication between children and social workers during child protection and welfare assessments. The data collection was designed to establish the thoughts and/or experiences of participants in relation to a Play Skills Training (PST) programme designed by the authors. The key findings of the study reveal that the majority of social work participants rate the use of play skills in social work assessments as a key factor to effective engagement with children. Of particular importance, these messages address how social work services can ensure in a child-centred manner that the voice of children is heard and represented in all assessments of their well-being and future care options. PMID- 27559223 TI - A Minority Report for Social Work? The Predictive Risk Model (PRM) and the Tuituia Assessment Framework in addressing the needs of New Zealand's Vulnerable Children. AB - This article examines the viability of the Risk Predictor Model (RPM) and its counterpart the actuarial risk assessment (ARA) tool in the form of the Tuituia Assessment Framework to address child vulnerability in New Zealand. In doing so, it suggests that these types of risk-assessment tools fail to address issues of contingency and complexity at the heart of the relationship-based nature of social work practice. Such developments have considerable implications for the capacity to enhance critical reflexive practice skills, whilst the introduction of these risk tools is occurring at a time when the reflexive space is being eroded as a result of the increased regulation of practice and supervision. It is further asserted that the primary aim of such instruments is not so much to detect risk, but rather to foster professional conformity with these managerialist risk-management systems so prevalent in contemporary Western societies. PMID- 27559224 TI - Adolescent-to-Parent Violence in Adoptive Families. AB - Adolescent-to-parent violence (APV) has received little attention in the social work literature, although it is known to be a factor in families whose children are at risk of entry to care. The behaviour patterns that characterise APV include coercive control, domination and intimidation. Crucially, parental behaviours are compromised by fear of violence. This article discusses the unexpected findings from two recent adoption studies of previously looked after children in England and Wales. The studies exposed the prevalence of APV in the lives of families who had experienced an adoption disruption and those who were finding parenting very challenging. Two main APV patterns emerged: early onset (pre-puberty) that escalated during adolescence, and late onset that surfaced during puberty and rapidly escalated. The stigma and shame associated with APV delayed help seeking. The response from services was often to blame the adoptive parents and to instigate child protection procedures. There is an urgent need for a greater professional recognition of APV and for interventions to be evaluated with children who have been maltreated and showing symptoms of trauma. PMID- 27559225 TI - Evidence for Using Farm Care Practices to Improve Attachment Outcomes in Foster Children: A Systematic Review. AB - Anecdotal evidence suggests that care farming practices have the potential to provide positive outcomes for young people in foster-care and residential care environments. A systematic review (searching; CINAHL, Web of Knowledge, PsychInfo) was conducted to explore how participation in care farming initiatives impacts attachment in children in foster-care and what aspects of care farming initiatives provides positive attachment outcomes. The systematic review did not identify any research publication in care farming and foster-care. Therefore, it is imperative that practitioners realise that the evidence is lacking when using these types of interventions and keep a close account of the benefit and harms that may be encountered during the interaction processes. PMID- 27559226 TI - Street-Level Strategies of Child Welfare Social Workers in Flanders: The Use of Electronic Client Records in Practice. AB - The use of information and communication technology (ICT) in child welfare services has increased significantly during the last decades, and so have the possibilities to process health data. Parton (2009) states that this evolution has led to a shift in the nature of social work itself: from 'the social' to 'the informational'. It is claimed that social workers primarily are becoming information processors concerned with the gathering, sharing and monitoring of information, instead of being focused on the relational dimensions of their work. However, social workers have considerable discretion concerning the way they use ICT. In this paper, we investigate (i) the street-level strategies social workers develop regarding ICT and (ii) how these relate to a narrative social work approach. To illustrate this, an evaluation of Charlotte was conducted, a client registration system that is used by social workers in child welfare services in Flanders, Belgium. Based on fifteen interviews, we find that social workers develop various strategies regarding Charlotte to preserve a relational and narrative work approach. These strategies not only result in a gap between ICT policy and the execution of that policy in practice, but also decrease the extent to which accountability can be realised via registration data. PMID- 27559227 TI - Coming Up for Air: Exploring an Intergenerational Perspective on Social Work. AB - From the late 1980s until now, scholars, educators and social workers have criticised the diminution of interest in the structural level of social problems. In this lament, former social work is beguiled, while critiques are targeted at the new generation of social workers. These critiques forewarn of important issues and problems, but at the same time they portray social work in a devolutionary way. It is argued that this one-sided debate conceals frictions between different generations of social workers. In reference to the work of Karl Mannheim, an intergenerational perspective is proposed that goes beyond nostalgic relishing of the past and calls on social work to actively engage with past remembrance and present evolutions. PMID- 27559228 TI - Comparative Performance of Adult Social Care Research, 1996-2011: A Bibliometric Assessment. AB - Decision makers in adult social care are increasingly interested in using evidence from research to support or shape their decisions. The scope and nature of the current landscape of adult social care research (ASCR) need to be better understood. This paper provides a bibliometric assessment of ASCR outputs from 1996 to 2011. ASCR papers were retrieved using three strategies: from key journals; using keywords and noun phrases; and from additional papers preferentially citing or being cited by other ASCR papers. Overall, 195,829 ASCR papers were identified in the bibliographic database Scopus, of which 16 per cent involved at least one author from the UK. The UK output increased 2.45-fold between 1996 and 2011. Among selected countries, those with greater research intensity in ASCR generally had higher citation impact, such as the USA, UK, Canada and the Netherlands. The top five UK institutions in terms of volume of papers in the UK accounted for 26 per cent of total output. We conclude by noting the limitations to bibliometric analysis of ASCR and examine how such analysis can support the strategic development of the field. PMID- 27559229 TI - Acquired Brain Injury, Social Work and the Challenges of Personalisation. AB - Increasing numbers of adults in the UK are living with acquired brain injury (ABI), with those affected requiring immediate medical care and longer-term rehabilitative and social care. Despite their social needs, limited attention has been paid to people with ABI within the social work literature and their needs are also often overlooked in policy and guidance. As a means of highlighting the challenge that ABI presents to statutory social work, this paper will start by outlining the common characteristics of ABI and consider the (limited) relevant policy guidance. The particular difficulties of reconciling the needs of people with ABI with the prevailing orthodoxies of personalisation will then be explored, with a particular focus on the mismatch between systems which rest on presumptions autonomy and the circumstances of individuals with ABI-typified by executive dysfunction and lack of insight into their own condition. Composite case studies, drawn from the first author's experiences as a case manager for individuals with ABI, will be used to illustrate the arguments being made. The paper will conclude by considering the knowledge and skills which social workers need in order to better support people with ABI. PMID- 27559230 TI - Coping with the Obligation Dilemma: Prototypes of Social Workers in the Nursing Home. AB - We examined the ways in which the social worker is coping with obligation dilemma in an Israeli nursing home. The research was conducted using semi-structured, in depth interviews carried out with fifteen social workers employed in nursing homes. The interviews were analysed thematically, using constant comparisons. The three themes were concerned with the social worker's place in the nursing home, her relationship with the management and staff, and her coping with the obligation dilemma. These themes highlighted the difference between the interviewees. On the background of this difference, four prototypes of nursing home's social workers were defined: the managerial, the contented, the fighter and the frustrated. From analysing the findings, the significant place of the personal and environmental factors that influence the ways in which the social worker deals with these four themes emerges. Our findings suggest that the strengthening, empowerment and support of social workers in institutions can directly enhance the health, security, emotional well-being and quality of life of nursing home residents. PMID- 27559231 TI - Reflections on Working with Vulnerable Women: Connecting, Cans of Worms, Closures and Coping. AB - This paper brings a close analysis to bear on tensions in the main discourses within probation and the wider criminal justice system, namely between punitive, target-driven approaches and the opposing gender-responsive, strengths-based, humanitarian, individualised ones. Drawing on a pilot study, which is an early part of the author's Ph.D., the article explores how probation practitioners attempt to work constructively within the constraints of statutory supervision and how the pressures and dilemmas are managed. Qualitative research methods were used whereby data were collected through videoing the supervision sessions of probation officers and women service users, as well as participant observation at probation meetings and in probation offices. Preliminary findings present new perspectives on current debates. Approaches of holistic women's centres are looked at alongside those of probation. The paper argues that, rather than imposing a probation framework onto these voluntary organisations, it is their philosophical underpinnings and structures, placing individuals' social needs at the forefront of practice with women and supporting practitioners to do so, which should be adopted formally within probation settings-Community Rehabilitation Companies (CRCs) and the National Probation Service (NPS). PMID- 27559232 TI - The Effects of Skill Training on Social Workers' Professional Competences in Norway: Results of a Cluster-Randomised Study. AB - Using a cluster-randomised design, this study analyses the effects of a government-administered skill training programme for social workers in Norway. The training programme aims to improve social workers' professional competences by enhancing and systematising follow-up work directed towards longer-term unemployed clients in the following areas: encountering the user, system-oriented efforts and administrative work. The main tools and techniques of the programme are based on motivational interviewing and appreciative inquiry. The data comprise responses to baseline and eighteen-month follow-up questionnaires administered to all social workers (n = 99) in eighteen participating Labour and Welfare offices randomised into experimental and control groups. The findings indicate that the skill training programme positively affected the social workers' evaluations of their professional competences and quality of work supervision received. The acquisition and mastering of combinations of specific tools and techniques, a comprehensive supervision structure and the opportunity to adapt the learned skills to local conditions were important in explaining the results. PMID- 27559234 TI - Pargament's Theory of Religious Coping: Implications for Spiritually Sensitive Social Work Practice. AB - This article proposes that Pargament's theory of religious coping can be a theoretical beacon to spiritually sensitive social work practice. It begins with a discussion of the raison d'etre of spiritually sensitive social work, which is examined as being able to cast a holistic and positive glow on social work. Then it provides an overview and a critique of Pargament's theory, emphasising that the theory offers a fuller and more impartial picture of religious coping. In addition, it explores the implications of Pargament's theory for spiritually sensitive social work practice with religious clients in terms of engagement, assessment and intervention. This article concludes by discussing how social work practitioners can avoid the pitfalls and limitations of Pargament's theory. PMID- 27559233 TI - Spiritually Sensitive Social Work with Victims of Natural Disasters and Terrorism. AB - As a primary intervention, raising the topics of faith and religion with individuals traumatised by terrorism and/or natural disasters can be daunting for social workers, because victims often enter the helping relationship with feelings of helplessness, loss of personal control and of doubt about their relationships, environment, and their cultural and belief systems. Just as clients benefit from knowledge and awareness in the aftermath of a traumatic event, insights gleaned from traumatic experiences and from research can be useful for social workers grappling with the challenges associated with designing and deploying appropriate helping strategies with victims of disaster and terrorism. This article draws on extant literature and survey research, to explore how social workers might ethically assess clients' spiritual perspectives and incorporate helping activities that support clients' recovery, in the context of a spiritually sensitive helping relationship with victims of disaster and terrorism. PMID- 27559235 TI - Exploring the Sacred-Secular Dialect in Everyday Social Work Practice: An Analysis of Religious Responses to Managerialism among Outreach Social Workers in Hong Kong. AB - We examine the recent proliferation of religious discourses among front line social workers in the former British Colony of Hong Kong in order to explore the nature of 're-enchantment' in modern social work practice. In-depth qualitative interviews with twenty social workers who identify as 'Christian social workers' in a variety of social work organisations (both religious and secular) reveal the adoption of religious identities and discourses to navigate the encroachment of managerialism. A systematic analysis of these narratives suggests that Christian social workers evoke religion to reclaim feelings of authenticity in their work, to facilitate more personalised relationships with their clients, and to empower themselves following the introduction of managerialist policies. We illuminate the dialectical relationship between religious discourses and managerialism to critique claims in the literature about a 're-enchantment' in social work, and to understand the essence of religion in modern social work practice. PMID- 27559236 TI - Articulating Connections between the Harm-Reduction Paradigm and the Marginalisation of People Who Use Illicit Drugs. AB - In this paper, we argue for the importance of unsettling dominant narratives in the current terrain of harm-reduction policy, practice and research. To accomplish this, we trace the historical developments regarding the Human Immunodeficiency Virus (HIV), the Hepatitis C Virus (HCV) and harm-reduction policies and practice. We argue that multiple historical junctures rather than single causes of social exclusion engender the processes of marginalisation, propelled by social movements, institutional interests, state legislation, community practices, neo-liberalism and governmentality techniques. We analyse interests (activist, lay expert, institutional and state) in the harm-reduction field, and consider conceptualisations of risk, pleasure, stigma, social control and exclusionary moral identities. Based on our review of the literature, this paper provides recommendations for social workers and others delivering health and social care interested in the fields of substance use, HIV prevention and harm reduction. PMID- 27559237 TI - After the Biomedical Technology Revolution: Where to Now for a Bio-Psycho-Social Approach to Social Work? AB - In the late twentieth century, the bio-psycho-social framework emerged as a powerful influence on the conceptualisation and delivery of health and rehabilitation services including social work services in these fields. The bio psycho-social framework is built on a systems view of health and well-being ( Garland and Howard, 2009). The systems perspective encourages medical and allied health professions, including social work, to recognise and to respond to the multiple systems impacting on individual health and well-being ( Engel, 2003). This paper analyses how advances in biomedical technology, particularly in the fields of neuroscience and human genomics, are challenging the bio-psycho-social approach to practice. The paper examines the pressures on the social work profession to embrace biomedical science and points to the problems in doing so. The conclusion points to some tentative ways forward for social workers to engage critically with biomedical advances and to strengthen the bio-psycho-social framework in the interests of holistic and ethical approaches to social work practice. PMID- 27559238 TI - The Unheard Gender: The Neglect of Men as Social Work Clients. AB - This critical review shows that, despite increasing attention to fathers in social work practice and research, men are still largely the 'unheard gender'. Almost all the social work literature that deals with men discusses them as fathers, namely in terms of their function in the family. Very little of it looks at men in other roles or situations or concerns itself with men's experiences, feelings or needs. Similar neglect of men characterises social work practice and training. The review points to a vicious circle in which the neglect of men in research, practice and training reinforce one another. It offers explanations for the neglect and suggestions for how to better include men as social work clients. PMID- 27559239 TI - A comparison of the anatomical structure of the pancreas in experimental animals. AB - As basic knowledge for evaluation of pancreatic toxicity, anatomical structures were compared among experimental animal species, including rats, dogs, monkeys, and minipigs. In terms of gross anatomy, the pancreases of dogs, monkeys, and minipigs are compact and similar to that of humans. The rat pancreas is relatively compact at the splenic segment, but the duodenal segment is dispersed within the mesentery. In terms of histology, the islet of each animal is characterized by a topographic distribution pattern of alpha- versus beta-cells. beta-cells occupy the large central part of the rat islet, and alpha-cells are located in the periphery and occasionally exhibit cuffing. In dog islets, beta cells are distributed in all parts and alpha-cells are scattered in the center or periphery of the islet (at body and left lobe); whereas beta-cells occupy all parts of the islet and no alpha-cells are present in the islet (at right lobe). Monkey islets show two distinct patterns, that is, alpha-cell-rich or beta-cell rich islets, and the former represent peripheral beta-cells forming an irregular ring. Minipig islets show an irregular outline, and both alpha- and beta-cells are present in all parts of the islet, intermingling with each other. According to morphometry, the endocrine tissue accounts for <2% of the pancreas roughly in rats and minipigs, and that of monkeys accounts for >7% of the pancreas (at tail). The endocrine tissue proportion tends to increase as the position changes from right to left in the pancreas in each species. PMID- 27559240 TI - Comparative histopathology of the estrous or menstrual cycle in laboratory animals. AB - Accurate analysis of female reproductive toxicity requires a thorough understanding the differences in and specifics of estrous or menstrual cycles between laboratory animals. There are some species differences such as the time of sex maturation, the length of the estrous or menstrual cycle, the length of the luteal phase, the number of dominant follicles or corpora lutea, the size of follicles, processes of luteinization, and hormonal changes during the estrous or menstrual cycle. Rodents have a short estrous cycle, and their ovarian cycling features are the same in both ovaries, which contain a large number of follicles and corpora lutea. The dog estrous cycle is much longer than those of other laboratory animals, and it includes a long anestrus phase. The duration of the menstrual cycle of monkeys is roughly 30 days, and their ovarian cycling features are different between the left and right ovaries. In both rodents and dogs, the theca cells invade the early luteum, mixing with granulosa cells during luteinization. However in monkeys, the theca layer dose not mix with the granulosa cells as it invaginates only slightly into the early luteum. In addition, we found that high progesterone levels after ovulation are sustained for a much shorter duration in rodents than in dogs and monkeys due to the comparatively rapid passage of the rodent luteal phase. Based on these species differences, animal species for use in ovarian toxicology studies need to be selected appropriately. PMID- 27559241 TI - Combretastatin A4 disodium phosphate-induced myocardial injury. AB - Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. PMID- 27559242 TI - Effect of methotrexate exposure at middle gestation on the inner plate of the ocular cup and lens in the rat fetus. AB - Pregnant rats were treated intraperitoneally with a single dose of methotrexate (MTX) 90 mg/kg on gestation day (GD) 13, and fetal eyeballs were examined time dependently from GD 13.5 to 15.5. Throughout the experimental period, the inner plate of the ocular cup in the MTX group was significantly thinner than that in the control group. In the inner plate of the ocular cup on GD 15 and 15.5, whereas a developed ganglion cell layer was observed in the control group, the ganglion cell layer in the MTX group was undeveloped and indistinguishable. Disturbance of the arrangement of lens fiber cells, narrowing of the hyaloid cavity of the optic cup, and hypoplasia of optic nerve fibers were observed in the MTX group on GD 15 and 15.5. Increase of pyknosis and decrease of mitosis were induced in the optic cup and the lens epithelium of the MTX group. In the inner plate of the optic cup and the lens epithelium of the MTX group, the cleaved caspase-3- and TUNEL-positive rates increased significantly throughout the experimental period. The phospho-histone H3-positive rate in the inner plate of the optic cup decreased significantly from GD 13.5 to 14.5, and it recovered on GD 15. On the other hand, the phospho-histone H3-positive rate in the lens epithelium decreased significantly throughout the experimental period. These results suggested that optic tissue on GD 13 in rats was sensitive to MTX. PMID- 27559243 TI - Accumulation of brown pigment-laden macrophages associated with vascular lesions in the lungs of cynomolgus monkeys(Macaca fascicularis). AB - Accumulation of macrophages containing brown pigments in the lungs is a well known spontaneous lesion found in cynomolgus monkey. However, its pathogenesis has not been clearly described. In our survey, brown pigment-laden macrophages were found in the lungs of 4 out of 43 cases. Brown pigments were mostly found in the macrophages of the perivascular interstitium, which proved to be hemosiderin. Some small- to medium-sized vessels that exhibited prominent accumulation of brown pigment-laden macrophages showed degeneration and necrosis of the smooth muscle cells of tunica media. Furthermore, ruptures of the internal and external elastic laminae were seen in some of the vessels. These findings suggested that partial fragmentation of the vascular elastic lamina followed by degeneration and necrosis of the tunica media caused blood leakage leading to the accumulation of hemosiderin-laden macrophages in the perivascular interstitium of the lungs. PMID- 27559244 TI - Spontaneous carcinosarcoma originating from the renal pelvis ina rat. AB - Carcinosarcoma is a rare neoplasm composed of malignant epithelial and stromal elements, and, for rats, carcinosarcomas in the kidney have not been reported. In a long-term study to gather background data, we encountered a spontaneous carcinosarcoma originating from the renal pelvis with metastasis to the lung. At necropsy, a mass was observed in the abdominal cavity, and white nodules were scattered in lung lobes. Microscopically, there was polypoid hyperplasia of the urothelium accompanied by hyperplasia of spindle stromal cells in the pelvis. The intra-abdominal tumor was composed of epithelial and stromal elements; in the lung, the tumor cells invaded along alveoli/bronchi and occasionally invaded the parenchyma from the blood vessels. Immunohistochemical and electron microscopic examinations revealed that the epithelial element consisted of transitional epithelial cells and that the stromal element consisted of lipoblasts. The tumor was diagnosed as a carcinosarcoma originating from the renal pelvis, and this is the first report of a carcinosarcoma originating from the renal pelvis in a rat. PMID- 27559245 TI - Neuroblastoma at the trigeminal nerve in a cynomolgus monkey (Macaca fascicularis). AB - A male cynomolgus monkey (Macaca fascicularis) of 5 years and 11 months of age from the vehicle control group of a 4-week repeated oral dose toxicity study had a spontaneously occurring mass lesion directly attached to the proximal part of the left trigeminal nerve. Histologically, the mass was characterized by a multifocal nodular appearance. Nodular zones showed low to moderate cellularity and were composed of small round cells exhibiting nuclear uniformity. On the other hand, inter-nodular zones were composed of nerve fiber containing septa and closely aggregated highly pleomorphic cells. Immunohistochemically, the small round cells were strongly immunopositive for synaptophysin, neuN, and class III beta-tubulin, while the highly pleomorphic cells were weakly immunopositive for neuN and occasionally immunopositive for class III beta-tubulin and doublecortin, suggesting that the tumor had originated from a neuronal lineage cell. Based on these findings, the mass was diagnosed as a neuroblastoma at the trigeminal nerve. PMID- 27559246 TI - Spontaneous malignant craniopharyngioma in an aged Wistar rat. AB - Craniopharyngiomas are extremely rare epithelial tumors of the sellar region in human beings and domestic and laboratory animals. A craniopharyngioma, 0.6 cm in diameter, was observed grossly in the sellar and parasellar regions of an untreated 23-month-old male Wistar-derived rat sacrificed moribund. The tumor was composed of cords, columns, and nests of neoplastic stratified squamous epithelium with marked hyperkeratosis and parakeratosis. Neoplastic cells formed solid or cystic areas, infiltrating the base of the skull, brain, and pituitary gland. Immunocytochemical evaluation revealed a strong cytoplasmic reaction for pan-cytokeratin in all tumor cells. Malignant craniopharyngioma should be considered a differential diagnosis in the rat when a tumor with stratified squamous epithelial features and a locally aggressive growth pattern is observed in the sellar or suprasellar region. PMID- 27559247 TI - Historical control background incidence of spontaneous thyroid and parathyroid glands lesions of rats and CD-1 mice used in 104-week carcinogenicity studies. AB - The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3.53%). In Han-Wistar rats, thyroid proliferative lesions were slightly more frequent in males than in females, but in Sprague-Dawley rats, they were of similar incidence in both sexes. The most common findings overall in Han-Wistar and Sprague-Dawley rats were C-cell hyperplasia (48.11% and 36.56%, respectively) and adenoma (10.87% and 9.52%, respectively), follicular cell hyperplasia (4.21% and 0.91%, respectively) and adenoma (4.32% and 1.36%, respectively). Secondary neoplastic lesions either in thyroid or parathyroid gland were poorly represented. PMID- 27559248 TI - Fusarenon-X-induced apoptosis in the liver, kidney, and spleen of mice. AB - Fusarenon-X is a non-macrocyclic type B trichothecene mycotoxin. It occurs naturally in agricultural commodities, such as wheat and barley. We investigated fusarenon-X-induced apoptosis in the liver, kidney, and spleen of male and female mice after a single exposure. Thus, mice were orally administered fusarenon-X (4 mg/kg body weight) and were assessed at 0, 3, 9, 18, 24, and 48 hours after treatment. Apoptosis in the liver, kidney, and spleen was determined using hematoxylin and eosin staining, the terminal deoxynucleotidyl transferase dUTP nick end labeling method, immunohistochemistry for proliferating cell nuclear antigen, and electron microscopy. Fusarenon-X-induced apoptosis at 9 hours after treatment, particularly hepatocytes around the central lobular zone of the liver, in proximal tubular cells of the kidney, and in hematopoietic cells in the red pulp area of the spleen in both male and female mice. The results of this study should be very useful with regard to the toxicity of fusarenon-X in both humans and domestic animals, which has been attributed to the intake of food contaminated with mycotoxins, especially fusarenon-X. PMID- 27559249 TI - Development of Specialist Palliative Care in Indian Cancer Care Setting: A Personal Journey of Three Decades. PMID- 27559250 TI - We have a Responsibility. PMID- 27559251 TI - Palliative Care in Musculoskeletal Oncology. AB - Patients in advanced stages of illness trajectories with local and widespread musculoskeletal incurable malignancies, either treatment naive or having recurrence are referred to the palliative care clinic to relieve various disease related symptoms and to improve the quality of life. Palliative care is a specialized medicine that offers treatment to the disease-specific symptoms, places emphasis on the psychosocial and spiritual aspects of life and help the patients and their family to cope with advance stage cancer in a stronger and reasonable way. The overall outcome of musculoskeletal malignancies has improved with the advent of multidisciplinary management. Even then these tumors do relapse and leads to organ failures and disease-specific deaths in children and young adults in productive age group thus requiring an integrated approach to improve the supportive/palliative care needs in end-stage disease. In this article, we would like to discuss the spectrum of presentation of advanced musculoskeletal malignancies, skeletal metastasis, and their management. PMID- 27559252 TI - Integration of Early Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Critical Review of Evidence. AB - INTRODUCTION: World Health Organization and American Society of Clinical Oncology recommend early integration of specialist palliative care in patients with cancer. This paper focuses on critical review of evidence on integration of early specialist palliative care in cancer care and patient-related outcomes. METHODS: The question for the literature search was - Does integration of early specialist palliative care in cancer care influences patient-related outcomes? 31 articles related to literature search review question were included in this paper. RESULTS: Ten patient-related outcomes of early specialist palliative care in adult cancer care was studied. Studies by Temel et al. (2012), Bakitas et al. (2009), Zimmermann et al. (2014), Rugno et al. (2014), Lowery et al. (2013) and Walker et al. (2014) showed early specialist palliative care improves health related quality of life (HRQOL). Studies by Pirl et al. (2012), Lowery et al. (2013), and Walker et al. (2014) showed early specialist palliative care improved mood depression and anxiety. Studies by Zimmermann et al. and Rugno et al. (2014) showed symptom control benefit of early specialist palliative care. Studies by Temel (2010), Bakitas (2015) and Rugno et al. (2014) showed survival improvement with early specialist palliative care. All these studies were carried in ambulatory palliative care setting. No survival benefit of palliative care intervention was seen in inpatient palliative care setting. The studies by Geer et al. (2012), Rugno et al. (2014), and Lowery et al. (2013) showed that early palliative care intervention positively influences treatment decision making. All the studies showed that palliative care intervention group received less intravenous chemotherapy in last few weeks of life. Studies by Yoong et al. and Temel et al. (2011) shows early specialist palliative care improves advanced care planning. Studies by Temel et al. (2010), Greer et al. (2012), McNamara et al. (2013), Hui et al. (2014), and Kwon et al.(2013) showed that early specialist palliative care improves health care utilization, planned discharge, less emergency room visits, and better hospice utilization. Studies by Wiese et al. (2013), Hui et al. (2014) and Temel et al. (2010) showed that early specialist palliative care improves end-of-life care outcomes. Study by Rugno et al. (2014) showed that early specialist palliative care improves health-related communication. Studies by Wallen et al. (2012) and Zimmermann et al. (2014) shows early specialist palliative care improves patient and family satisfaction. There is a lack of robust evidence at present to support role of early specialist palliative care interventions in pediatric and geriatric oncology. Qualitative studies have demonstrated few negative outcomes of early specialist palliative care intervention. CONCLUSIONS: In adult oncology, there is evidence to suggest early specialist palliative care improves HRQOL, mood, treatment decision-making, health care utilization, advanced care planning, patient satisfaction, and end-of life care. There is moderate evidence to support the role of early specialist palliative care intervention in improvement of symptoms, survival, and health related communication. There is limited evidence at present to support role of early specialist palliative care interventions in pediatric and geriatric oncology. Qualitative studies on barriers and negative patient outcomes may provide useful insights toward restructuring early specialist palliative care interventions. PMID- 27559253 TI - Integration of Early Specialist Palliative Care in Cancer Care: Survey of Oncologists, Oncology Nurses, and Patients. AB - INTRODUCTION: Palliative care is usually delivered late in the course of illness trajectory. This precludes patients on active disease modifying treatment from receiving the benefit of palliative care intervention. A survey was conducted to know the opinion of oncologists, oncology nurses, and patients about the role of early specialist palliative care in cancer. METHODS: A nonrandomized descriptive cross-sectional study was conducted at a tertiary cancer care center in India. Thirty oncologists, sixty oncology nurses, and sixty patients were surveyed. RESULTS: Improvement in symptom control was appreciated by oncologists, oncology nurses, and patients with respect to pain (Z = -4.10, P = 0.001), (Z = -5.84, P = 0.001), (Z = -6.20, P = 0.001); nausea and vomiting (Z = -3.75, P = 0.001), (Z = 5.3, P = 0.001), (Z = -5.1, P = 0.001); constipation (Z = -3.29, P = 0.001), (Z = -4.96, P = 0.001), (Z = -4.49, P = 0.001); breathlessness (Z = -3.57, P = 0.001), (Z = -5.03, P = 0.001), (Z = -4.99, P = 0.001); and restlessness (Z = -3.68, P = 0.001), (Z = -5.23, P = 0.001), (Z = -3.22, P = 0.001). Improvement in end-of life care management was appreciated by oncologists and oncology nurses with respect to communication of prognosis (Z = -4.04, P = 0.001), (Z = -5.20, P = 0.001); discussion on limitation of life-sustaining treatment (Z = -3.68, P = 0.001), (Z = -4.53, P = 0.001); end-of-life symptom management (Z = -4.17, P = 0.001), (Z = -4.59, P = 0.001); perimortem care (Z = -3.86, P = 0.001), (Z = 4.80, P = 0.001); and bereavement support (Z = -3-80, P = 0.001), (Z = -4.95, P = 0.001). Improvement in health-related communication was appreciated by oncologists, oncology nurses, and patients with respect to communicating health related information in a sensitive manner (Z = -3.74, P = 0.001), (Z = -5.47, P = 0.001), (Z = -6.12, P = 0.001); conducting family meeting (Z = -3.12, P = 0.002), (Z = -4.60, P = 0.001), (Z = -5.90, P = 0.001); discussing goals of care (Z = 3.43, P = 0.001), (Z = -5.49, P = 0.001), (Z = -5.61, P = 0.001); maintaining hope (Z = -3.22, P = 0.001), (Z = -4.85, P = 0.001), (Z = -5.61, P = 0.001); and resolution of conflict (Z = -3.56, P = 0.001), (Z = -5.29, P = 0.001), (Z = 5.28, P = 0.001). Patients appreciated improvement in continuity of care with respect to discharge planning (Z = -6.12, P = 0.001), optimal supply of essential symptom control medications on discharge (Z = -6.32, P = 0.001), follow-up plan (Z = -6.40, P = 0.001), after hours telephonic support (Z = -6.31, P = 0.001), and preferred place of care (Z = -6.28, P = 0.001). CONCLUSION: Oncologists, oncology nurses, and patients felt that integration of early specialist palliative care in cancer improves symptom control, end-of-life care, health related communication, and continuity of care. The perceptions of benefit of the palliative care intervention in the components surveyed, differed among the three groups. PMID- 27559254 TI - Specialist Pediatric Palliative Care Referral Practices in Pediatric Oncology: A Large 5-year Retrospective Audit. AB - PURPOSE: To audit referral practices of pediatric oncologists referred to specialist pediatric palliative care services. PATIENTS AND METHODS: Retrospective review of medical case records of pediatric palliative care patients over a period of 5 years from January 1, 2010 to December 31, 2014. Descriptive summaries of demographic, clinical variables, and patient circumstances at the time of referral and during end-of-life care were examined. RESULTS: A total of 1135 patients were referred from pediatric oncology with a gradual increasing trend over 5 years. About 84.6% consultations took place in the outpatient setting. In 97.9% of the cases, parents were the primary caregivers. Availability of specialist pediatric health-care services at local places was available in 21.2% cases and 48% families earned <5000 INR (approximately 73 USD) in a month. Around 28.3% of the referrals were from leukemia clinic and maximum references were late with 72.4% patients having advanced disease at presentation. 30.3% of the referrals were made for counseling and communication and 54.2% had high symptom burden during referral. After referral, 21.2% patients continued with oral metronomic chemotherapy and 10.5% were referred back to oncology services for palliative radiotherapy. Only 4.9% patients had more than 2 follow-ups. 90.8% of the patients were cared for at home in the last days of illness by local general practitioners. 70.6% of the deaths were anticipated. CONCLUSIONS: Oncologists referred patients late in the course of disease trajectory. Most of the referrals were made for counseling and communication, but many patients had high symptom burden during referral. PMID- 27559255 TI - Specialist Pediatric Palliative Care Prescribing Practices: A Large 5-year Retrospective Audit. AB - INTRODUCTION: There is a gradual increasing trend in childhood cancers in India and pediatric palliative care in India is an emerging specialty. Prescribing pain and symptom control drugs in children with cancer requires knowledge of palliative care formulary, dosing schedules, and prescription guidelines. This study is a retrospective audit of prescribing practices of a specialist palliative care service situated in a tertiary cancer center. METHODS: A total of 1135 medication records of children receiving specialist pediatric palliative care services were audited for 5 years (2010-2014) to evaluate prescribing practices in children with advanced cancer. RESULTS: A total of 51 types of drugs were prescribed with an average of 4.2 drugs per prescription. 66.9% of the prescriptions had paracetamol, and 33.9% of the prescriptions had morphine. Most common nonsteroidal anti-inflammatory drugs prescribed was ibuprofen (23.9%), and more than 50% of the prescriptions had aperients. The most commonly prescribed aperient was a combination of liquid paraffin and sodium-picosulfate. Dexamethasone was prescribed in 51.9% of patients and in most cases this was part of oral chemotherapy regimen. Generic names in prescription were used only in 33% of cases, and adverse effects of the drugs were documented in only 9% of cases. In 25% of cases, noncompliance to the WHO prescription guidelines was seen, and patient compliance to prescription was seen in 40% of cases. CONCLUSIONS: Audit of the prescribing practices in specialist pediatric palliative care service shows that knowledge of pediatric palliative care formulary, rational drug use, dosing, and prescribing guidelines is essential for symptom control in children with advanced life-limiting illness. Noncompliance to WHO prescribing guidelines in one fourth of cases and using nongeneric names in two-thirds of prescription indicates poor prescribing practices and warrants prescriber education. Prescription noncompliance by almost two-thirds of patients is alarming and necessitates intense patient, family, and caregiver education and empowerment. PMID- 27559256 TI - Patients with End-stage Interstitial Lung Disease may have More Problems with Dyspnea than End-stage Lung Cancer Patients. AB - INTRODUCTION: Patients with end-stage interstitial lung disease (ILD) do not appear to receive adequate palliative care despite apparent suffering before death. The aim of this study was to evaluate their signs, symptoms, and treatment received before death. METHODS: Patients with ILD and lung cancer (LC) who were hospitalized and died in our hospital were enrolled retrospectively. Signs and symptoms and treatments at 7 days, 3 days, and 1 day before death were evaluated and compared between the two groups of patients. RESULTS: A total of 23 patients with ILD and 59 patients with LC group were eligible for participation. Significantly more LC patients had loss of consciousness than ILD patients on 7 days (ILD: LC = 1 [5.6%]:24 [41%], P = 0.013), 3 days (1 [5.6%]:33 [56%], P < 0.001). Significantly more ILD patients had dyspnea than LC patients on 3 days (16 [89%]:38 [64%], P = 0.047) 1 day before death (21 [91%]:33 [56%], P = 0.001). On 1 day before death, significantly more LC patients received morphine than ILD patients (2 [8.7%]: 14 [24%], P = 0.015). More ILD patients received sedation (11 [48%]: 11 [19%], P = 0.007). CONCLUSIONS: End-stage ILD patients may experience dyspnea more frequently than terminal LC patients, and they need sedation. Morphine should be administered to ILD patients who have dyspnea. Additional prospective studies are needed. PMID- 27559257 TI - Factors Influencing Compliance to Radical Treatment of Middle Thoracic Esophageal Cancer: An Audit from a Regional Cancer Centre. AB - BACKGROUND: The aim of this study is to identify the factors responsible for interruption of planned treatment in patients of carcinoma mid-thoracic esophagus and also discuss the strategies for improving treatment completion rates. MATERIALS AND METHODS: Patients with nonmetastatic mid-thoracic esophageal cancer who received treatment by multimodality approach using chemotherapy, radiation, and/or surgery were retrospectively analyzed. Factors influencing compliance with planned treatment completion were evaluated, and their significance was determined using multivariate Cox regression analysis. RESULTS: Ninety-one patients were reviewed. Median follow-up period was 11 months. Of 15 patients planned with neoadjuvant chemoradiation followed by surgery (Group 1), only 6 (40%) could complete the treatment. Similarly, only 19 out of 36 patients (52.8%) completed the planned definitive chemoradiation (Group 2). Furthermore, of forty patients planned with definitive radiotherapy (Group 3), 29 patients only (72.5%) completed this schedule. The rate of completion of therapy was worst in Group 1. The most common reason for noncompletion of planned treatment was nutritional inadequacy and excessive weight loss in all groups. In addition, chemotherapy induced myelosuppression (P = 0.05) was the factor leading to treatment interruption in Group 2 and radiation-induced acute mucositis (P = 0.02) and lost to follow-up (P = 0.02) were the factors in Group 3. CONCLUSIONS: Rate of treatment completion significantly impacts survival rates. Nutritional inadequacy was the most common factor for noncompletion of planned treatment. A well-trained management team consisting of oncologist, dietitian, and psychotherapist can help overcome these factors and thereby improve the treatment completion rates. PMID- 27559258 TI - The Efficacy of Oral Melatonin in Improving Sleep in Cancer Patients with Insomnia: A Randomized Double-Blind Placebo-Controlled Study. AB - BACKGROUND: The natural hormone melatonin has sleep inducing properties. Insomnia in cancer patients is common. So far, melatonin has been seldom tried for the improvement of sleep in patients with malignancies. Keeping this in mind, we planned and conducted a double-blind study to test the efficacy of melatonin in promoting sleep in patients with malignancies suffering from insomnia. OBJECTIVE: To assess the hypnotic efficacy of oral melatonin in cancer patients with insomnia. MATERIALS AND METHODS: After Ethical Committee approval, 50 patients (age range 20-65 years) from our pain clinic NIVARANE who met the Diagnostic and Statistical Manual of Mental Disorders 4(th) edition criteria for primary insomnia were randomized to receive melatonin 3 mg or placebo at 7 pm orally every day for 14 days from our pharmacist. After 1, 7, 14 days, the patients were reviewed with the Athens insomnia scale oral questionnaire to document the subjective sleep quality. The patients and we, the investigators were blinded to the study drug. RESULTS: There were 2 drop outs (one from each group) as they failed to complete visit on day 14. Significant differences in favor of melatonin treatment were found in clinically relevant improvements in insomnia (46.53%; P = 0.00001 vs. 11.30%; P = 0.1026) There was improvement in sleep from 1 to 7 days (19.91%; P = 0.00001 vs. 0.98%; P = 0.2563). More significant improvements were seen between 7 and 14 days (33.24%; P = 0.00001 vs. 10.42%; P = 0.1469). CONCLUSION: We conclude that daily intake of oral melatonin 2 h before bedtime improves sleep induction and quality in cancer patients with insomnia. PMID- 27559259 TI - Comparative Evaluation of Retrocrural versus Transaortic Neurolytic Celiac Plexus Block for Pain Relief in Patients with Upper Abdominal Malignancy: A Retrospective Observational Study. AB - AIM: To compare retrocrural versus transaortic techniques for neurolytic celiac plexus block (NCPB) in patients suffering from upper abdominal malignancy. METHODS: In this retrospective observational study between October 2013 and April 2015, 64 patients with inoperable upper abdominal malignancy received fluoroscopy guided percutaneous NCPB in our institute. Their case files were reviewed and the patients were divided into two groups depending on the technique used to perform NCPB: retrocrural (Group R; n = 36) versus transaortic (Group T; n = 28). The primary outcome measure was pain as assessed with a numeric rating scale (NRS) from 0 to 10; the secondary outcome measures were morphine consumption per day (M), quality of life (QOL) as assessed by comparing the percent of positive responses in each group, and complications if any. These were noted and analyzed prior to intervention and then on day 1, weeks 1, 2, 3, and months 1, 2, 3, 6 following NCPB. RESULTS: Patients in Group R had significantly reduced NRS pain scores at week 1, 2, 3, month 1 and 2 as compared to Group T (P < 0.05). Morphine consumption also reduced significantly in Group R at day 1, week 1, 2, and 3 (P < 0.05). QOL was found to be comparable between the groups, and no major complications were noted. CONCLUSION: Retrocrural NCPB provides superior pain relief along with a reduction in morphine consumption as compared to transaortic NCPB in patients with pain due to upper abdominal malignancy. PMID- 27559260 TI - Effect of Music Therapy on Pain and Anxiety Levels of Cancer Patients: A Pilot Study. AB - BACKGROUND: The pain associated with cancer is highly detrimental to the quality of life of the affected individuals. It also contributes to the anxiety of the patient. There is a need for a nonpharmacological approach in addition to the pharmacological therapy for the management of the pain for a more holistic improvement in the individual. With this study, we wish to achieve this through music. OBJECTIVE: To assess the effect of music therapy on pain scores and anxiety levels of cancer patients with pain. STUDY DESIGN: In this quantitative study, a comparative study was done on fourteen cancer patients admitted for pain relief under the Department of Pain and Palliative Medicine, of a tertiary care hospital, having moderate to severe pain (numerical pain rating scale [NRS] - of 4 to 10). SUBJECTS AND METHODS: Convenience sampling was used. Patients were allocated to test group or control group nonrandomly. The test group patients were subjected to music therapy for 20 min while the control group patients were kept occupied by talking to them for 20 min. The NRS scale was used to assess the pre- and post-interventional pain scores and the Hamilton anxiety rating scale was used to assess the pre- and post-interventional anxiety scores in the two groups. STATISTICS: Student's t-test was used for comparing the pre- and post interventional data. Two sample t-test was used to compare the data obtained from the control and study groups. RESULTS: Statistically significant reduction seen in the pain scores in the test group after music therapy (P = 0.003). No statistically significant reduction seen in the pain score in the control group (P = 0.356). There was a statistically significant reduction in the postintervention pain scores in the test group compared to the control group (P = 0.034). The reduction in anxiety levels in both groups after intervention was not statistically significant. CONCLUSION: Music therapy was found to lower the pain score of a patient who had received standard palliative care for pain reduction. It was also more effective than the act of talking in reducing the pain score. A study with a larger sample size should be undertaken to conclude that, music therapy can be used in addition to morphine and other painkillers to reduce pain as a part of a more holistic approach to palliative care strategies. PMID- 27559261 TI - The Use of the Chuang's Prognostic Scale to Predict the Survival of Metastatic Colorectal Cancer Patients Receiving Palliative Systemic Anticancer Therapy. AB - BACKGROUND: With the increasing number of agents active against cancer, advanced cancer patients including metastatic colorectal cancer (mCRC) patients may continue receiving palliative systemic anticancer therapy (PSAT) near the end-of life. Validated palliative prognostic models, such as the Chuang's prognostic scale (CPS), may be helpful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT. AIM: To test the ability of the CPS to predict the survival of mCRC under treatment with PSAT. METHODS: CPS was prospectively assessed in 36 mCRC patients who were receiving PSAT. The scale is based on eight items: ascites, edema, cognitive impairment, liver and lung metastases, performance status, tiredness, and weight loss. The total CPS score ranges from 0 to 8.5 with the higher score indicating worse prognosis. RESULTS: Patients were divided into two groups using a CPS cutoff score of 5, Group 1 with a CPS score <=5 and Group 2 with a CPS score >5. Using this cutoff value, 3-month mortality was predicted with a positive predictive value of 71%, a negative predictive value of 77%, a sensitivity of 67%, a specificity of 81% and an overall accuracy of 75%. Group 1 patients had a longer median survival of 149 days (95% confidence interval [CI]: 82-216) in comparison to Group 2 patients who had a median survival of 61 days (95% CI: 35-87). The difference in survival was statistically significant (P = 0.01). CONCLUSION: CPS may be useful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT. PMID- 27559262 TI - Parent's Perspectives on the End-of-life Care of their Child with Cancer: Indian Perspective. AB - CONTEXT: Parents report that end-of-life decisions are the most difficult treatment-related decisions that they face during their child cancer experience. Research from the parent's perspective of the quality of end-of-life care of their cancer children is scarce, particularly in developing countries like India. AIMS: This study aimed to identify the symptoms (medical/social/emotional) that most concerned parents at the end-of-life care of their cancer child and to identify the strategies parents found to be helpful during this period. SETTINGS AND DESIGN: We wanted to conduct this to focus on the parents perspectives on their cancer child's end-of-life care and to address the issues that could contribute to the comfort of the families witnessing their child's suffering. MATERIALS AND METHODS: The study was conducted at Sri Ramachandra University, Chennai, a Tertiary Care Pediatric Hemato Oncology Unit. Parents who lost their child to cancer, treated in our institution were interviewed with a validated prepared questionnaire. Statistical analysis was performed using SAS statistical software package. RESULTS: Toward death, dullness (30%), irritability (30%), and withdrawn from surroundings (10%) were the most common symptoms encountered. About 30% of the children had fear to be alone. About 50% of the children had the fear of death. Pain, fatigue, loss of appetite were the main distressful symptoms that these children suffered from parents' perspective. Though the parents accepted that the child was treated for these symptoms, the symptom relief was seldom successful. CONCLUSION: The conclusion of the study was that at the end of their child's life, parents value obtaining adequate information and communication, being physically present with the child, preferred adequate pain management, social support, and empathic relationships by the health staff members. PMID- 27559263 TI - Why Newly Diagnosed Cancer Patients Require Supportive Care? An Audit from a Regional Cancer Center in India. AB - PURPOSE: The present study was planned to record the distressing symptoms of newly diagnosed cancer patients and evaluate how the symptoms were addressed by the treating oncologists. MATERIALS AND METHODS: All newly diagnosed cancer patients referred to the Department of Radiotherapy during May 2014 were asked to complete a questionnaire after taking their consent. The Edmonton symptom assessment scale-regular questionnaire was used to assess the frequency and intensity of distressing symptoms. The case records of these patients were then reviewed to compare the frequency and intensity documented by the treating physician. The difference in the two sets of symptoms documented was statistically analyzed by nonparametric tests using SPSS software version 16. RESULTS: Eighty-nine patients participated in this study, of which only 19 could fill the questionnaire on their own. Anxiety was the most common symptom (97.8%) followed by depression (89.9%), tiredness (89.9%), and pain (86.5%). The treating physicians recorded pain in 83.1% whereas the other symptoms were either not documented or grossly underreported. Anxiety was documented in 3/87 patients, but depression was not documented in any. Tiredness was documented in 12/80 patients, and loss of appetite in 54/77 patients mentioning them in the questionnaire. Significant statistical correlation could be seen between the presence of pain, anxiety, depression, tiredness, and loss of appetite in the patients. CONCLUSION: The study reveals that the distressing symptoms experienced by newly diagnosed cancer patients are grossly underreported and inadequately addressed by treating oncologists. Sensitizing the oncologists and incorporating palliative care principles early in the management of cancer patients could improve their holistic care. PMID- 27559264 TI - Self-image of the Patients with Head and Neck Cancer: A Mixed Method Research. AB - AIM: The aim of the study was to assess the self-image of the patients with head and neck cancers (HNCs) by using a mixed method research. SUBJECTS AND METHODS: A mixed method approach and triangulation design was used with the aim of assessing the self-image of the patients with HNCs. Data was gathered by using self administered self-image scale and structured interview. Nested sampling technique was adopted. Sample size for quantitative approach was 54 and data saturation was achieved with seven subjects for qualitative approach. Institutional Ethical Committee clearance was obtained. RESULTS: The results of the study showed that 30 (56%) subjects had positive self-image and 24 (44%) had negative self-image. There was a moderate positive correlation between body image and integrity (r = 0.430, P = 0.001), weak positive correlation between body image and self-esteem (r = 0.270, P = 0.049), and no correlation between self-esteem and integrity (r = 0.203, P = 0.141). The participants also scored maximum (24/24) in the areas of body image and self-esteem. Similar findings were also observed in the phenomenological approach. The themes evolved were immaterial of outer appearance and desire of good health to all. CONCLUSION: The illness is long-term and impacts the individual 24 h a day. Understanding patients' self-concept and living experiences of patients with HNC is important for the health care professionals to improve the care. PMID- 27559265 TI - Development of the Draft Clinical Guideline on How to Resuscitate Dying Patients in the Iranian Context: A Study Protocol. AB - INTRODUCTION: The guidelines can be used as a model to guide the implementation of the best options and a suitable framework for clinical decisions. Even a guideline can largely help in challenging problems such as not to resuscitate with high cultural and value load. The guidelines try to improve the health care quality through reducing the treatment costs and variety of care measures. This study aimed to prepare a draft of clinical guidelines with the main aim of designing and drafting the clinical guideline on resuscitation in dying patients. METHODOLOGY: After selecting the subject of this guideline, in the first meeting of the team members of drafting the guideline, the guideline scope was determined. Then, the literature review done without time limitation, through searching electronic bibliographic information and internet databases and sites such as Medline, EMBASE, Springer, Blackwell Synergy, Elsevier, Scopus, Cochran Library and also databases including SID, Iran Medex, and Magiran. The experts will be the interviewed, and the interviews are directed content analysis. CONCLUSION: Finally, recommendations will be formed by nominal group technique. This study protocol includes informative information for designing and conducting of health professionals intending to create a direct on qualitative, theoretical, philosophical, spiritual, and moral health aspects. PMID- 27559266 TI - Knowledge of Palliative Care Among Medical Interns in a Tertiary Health Institution in Northwestern Nigeria. AB - BACKGROUND: Palliative care is the proactive care which seeks to maximize quality of life for people and families facing life-threatening illnesses. OBJECTIVES: To ascertain the existing knowledge of palliative care among medical interns and determine the effect of a structured educational intervention on improvement of their knowledge levels. SUBJECTS AND METHODS: This is a quasi-experimental, interventional study with a one group pre- and post-test design involving medical interns rotating through the various departments of the Usmanu Danfodiyo University Teaching Hospital, Sokoto. The study population was chosen by convenience sampling method. The interns completed a pre- and a post-test assessment following a structured educational intervention for the evaluation of knowledge of palliative care. Knowledge was evaluated by a self-administered structured questionnaire. RESULTS: A total number of 49 medical interns were recruited, among whom were 41 males and 8 females. Their ages ranged from 21 to 36 years with a mean of 27.7 (standard deviation 2.14) years. In the pretest, 11/49 (22.5%) of the respondents had poor knowledge level of palliative care; however, in the postintervention, only 2/49 (4.1%) of the respondents had poor knowledge. Similarly, good knowledge levels appreciated from 9/49 (18.4%) to 14/49 (28.6%) while very good knowledge increased from 10/49 (20.4%) to 19/49 (38.8%). This effect was statistically significant (Chi-square test 11.655 df = 3, P = 0.009). CONCLUSION: There is poor knowledge of palliative care among the interns due to ignorance. Following an educational intervention, the knowledge levels appreciated significantly. Palliative care should be part of the medical curriculum. PMID- 27559267 TI - Motivation of Volunteers to Work in Palliative Care Setting: A Qualitative Study. AB - BACKGROUND: Volunteers are an integral part of the palliative care services in the Tata Memorial Hospital, Mumbai, Maharashtra, India. These volunteers are an important resource for the department. Thus, it is necessary for the department to determine what motivates these volunteers to continue to work in the setting, acknowledge them and direct efforts toward retaining them and giving them opportunities to serve to the best of their desire and abilities. AIMS: The current study aimed at understanding the motivation of volunteers to work in palliative care, to identify the challenges they face and also the effect of their work on their self and relationships. METHODOLOGY: In-depth interviews were conducted using semistructured interview guide to study above mentioned aspects. Themes were identified and coding was used to analyze the data. RESULTS: The results suggested that the basic motivation for all the volunteers to work in a palliative care setting is an inherent urge, a feeling of need to give back to the society by serving the sick and the suffering. Other motivating factors identified were team spirit, comfort shared, warm and respectful treatment by the team, satisfying nature of work, experience of cancer in the family, and aligned values and beliefs. Some intrinsic rewards mentioned by volunteers were joy of giving, personal growth, enriching experiences, and meaningful nature of work. CONCLUSION: The study attempted to improve opportunities of working for these volunteers. Although limited in scope, it offers insight for future research in the area of volunteerism in palliative care setup. PMID- 27559268 TI - The Attitude of Medical Students Toward Death: A Cross-Sectional Study in Rafsanjan. AB - AIM: Attitude toward death is one of the most important factors that can influence the behavior related to the health profession. It is thought that physicians are afraid of death more than other groups of specialist. Therefore, this study aimed to evaluate the attitudes of the medical students of Rafsanjan University of Medical Sciences toward death. MATERIALS AND METHODS: This study is a cross-sectional study on 308 medical students of Rafsanjan University of Medical Sciences in the academic year of 2015. Attitudes were assessed through the questionnaire of death attitude profile-revised. The collected data were analyzed upon arrival to a computer with SPSS version 14, and descriptive and inferential statistical methods. RESULTS: Attitude toward death was investigated in the 5 dimensions including the fear of death, death avoidance, approach acceptance, neutral acceptance, and escape acceptance. The results showed that the mean and standard deviations of fear of death, death avoidance, natural acceptance, approach acceptance, and escape acceptance were 3.76 +/- 1.15, 3.54 +/- 1.33, 5.14 +/- 0.86, 4.66 +/- 0.95, and 3.73 +/- 1.25, respectively. It was found that people who have had the experience in dealing with death had less escape of the death attitude. CONCLUSION: Totally, the results of this study demonstrated that the medical students had good attitudes through 5 dimensions of attitudes toward death. This is probably due to the religious beliefs and also dealing with dying patients. However, it is recommended that training programs should be provided for students in the field of attitudes toward death. PMID- 27559269 TI - The Influence of Demographic and Psychosocial Factors on the Intensity of pain Among Chronic Patients Receiving Home-based Nursing Care. AB - AIM: To determine the influence of the demographic and the psychosocial factors on the intensity of pain manifestation among the chronic ill patients. MATERIALS AND METHODS: A descriptive, cross-sectional study was carried out among 328 chronic patients under home-based nursing care in Southern State of Kerala, India, from July to August 2015. Each patient was interviewed during a scheduled home visit by a trained health professional. The translated version of the assessment tool questionnaire Medical Outcome Study-Short Form Health Survey was used for the data collection. RESULTS: Sixty-four (19.5%) out of 328 patients reported pain as one of the primary symptoms of their disease. The percentage of the patients who were suffering from pain increases with the improvements in both the educational level and the monthly income (P = 0.002 and 0.019, respectively). The social interaction with the relatives and other community members was significantly related to pain manifestation (P = 0.013). A higher degree of social interaction was associated with lower pain intensity (P = 0.019). CONCLUSION: The results of this study showed that certain demographic and psychosocial factors carry a significant level of influence on the pain manifestation and its intensity among the chronic patients. Hence, improvements in education, economic status, and psychosocial support should be considered for the management of the chronic patients. PMID- 27559270 TI - Circalunidian clocks control tidal rhythms of locomotion in the American horseshoe crab, Limulus polyphemus. AB - While many intertidal animals exhibit circatidal rhythms, the nature of the underlying endogenous clocks that control these rhythms has been controversial. In this study American horseshoe crabs, Limulus polyphemus, were used to test the circalunidian hypothesis by exposing them to four different tidal regimes. Overall, the results obtained support the circalunidian hypothesis: each of the twice-daily rhythms of activity appears to be controlled by a separate clock, each with an endogenous period of approximately 24.8h. First, spontaneous "skipping" of one of the daily bouts was observed under several different conditions. Second, the presence of two bouts of activity/day, with different periods, was observed. Lastly, we were able to separately synchronize bouts of activity to two artificial tidal regimes with different periods. These results, taken together, argue in favor of two separate circalunidian clocks in Limulus, each of which controls one of the two bouts of their daily tidal activity rhythms. PMID- 27559271 TI - Novel non-cyclooxygenase inhibitory derivatives of naproxen for colorectal cancer chemoprevention. AB - A structure-based medicinal chemistry strategy was applied to design new naproxen derivatives that show growth inhibitory activity against human colon tumor cells through a cyclooxygenase (COX)-independent mechanism. In vitro testing of the synthesized compounds against the human HT-29 colon tumor cell line revealed enhanced growth inhibitory activity compared to the parent naproxen with 3a showing IC50 of 11.4 MUM (two orders of magnitude more potent than naproxen). Selectivity of 3a was investigated against a panel of three tumor and one normal colon cell lines and showed up to six times less toxicity against normal colonocytes. Compound 3a was shown to induce dose-dependent apoptosis of HT116 colon tumor cells as evidenced by measuring the activity of caspases-3 and 7. None of the synthesized compounds showed activity against COX-1 or COX-2 isozymes, confirming a COX-independent mechanism of action. Compound 3k was found to have no ulcerogenic effect in rats as indicated by electron microscope scanning of the stomach after oral administration. A pharmacophore model was developed for elucidating structure-activity relationships and subsequent chemical optimization for this series of compounds as colorectal cancer chemopreventive drugs. PMID- 27559272 TI - Influenza Vaccination among Pregnant Women: Patient Beliefs and Medical Provider Practices. AB - ACOG's research department recruited four medical centers to participate in a study on the attitudes and practices of medical providers and pregnant patients regarding influenza vaccination. Medical providers and patients were given voluntary surveys and medical record data was collected over two flu seasons, from 2013 to 2015. Discrepancies between self-reports of medical providers and patients and medical records were observed. Nearly 80% of patients self-reported accepting the influenza vaccine, but medical record data only reported 36% of patients accepting the vaccine. Similarly, all medical providers reported giving recommendations for the vaccine, but only 85% of patients reported receiving a recommendation. Age, education, a medical provider's recommendation, and educational materials were found to positively influence patient beliefs about the influenza vaccine. Accepting the vaccine was influenced by a patient's previous actions, beliefs, and a medical provider's recommendation. Patients who reported previously not accepting the vaccine and had negative feelings towards the vaccine but accepted it while pregnant reported concern for the health and safety of their baby. Future research should focus on groups that may be less likely to accept the vaccine and ways to dispel negative myths. Medical provider should continue to strongly recommend the vaccine and provide educational materials. PMID- 27559273 TI - Welcome to JMMT's new editorial team. PMID- 27559274 TI - Manual unloading of the lumbar spine: can it identify immediate responders to mechanical traction in a low back pain population? A study of reliability and criterion referenced predictive validity. AB - BACKGROUND: To date, no research has examined the reliability or predictive validity of manual unloading tests of the lumbar spine to identify potential responders to lumbar mechanical traction. PURPOSE: To determine: (1) the intra and inter-rater reliability of a manual unloading test of the lumbar spine and (2) the criterion referenced predictive validity for the manual unloading test. METHODS: Ten volunteers with low back pain (LBP) underwent a manual unloading test to establish reliability. In a separate procedure, 30 consecutive patients with LBP (age 50.86+/-11.51) were assessed for pain in their most provocative standing position (visual analog scale (VAS) 49.53+/-25.52 mm). Patients were assessed with a manual unloading test in their most provocative position followed by a single application of intermittent mechanical traction. Post traction, pain in the provocative position was reassessed and utilized as the outcome criterion. RESULTS: The test of unloading demonstrated substantial intra and inter-rater reliability K = 1.00, P = 0.002, K = 0.737, P = 0.001, respectively. There were statistically significant within group differences for pain response following traction for patients with a positive manual unloading test (P<0.001), while patients with a negative manual unloading test did not demonstrate a statistically significant change (P>0.05). There were significant between group differences for proportion of responders to traction based on manual unloading response (P = 0.031), and manual unloading response demonstrated a moderate to strong relationship with traction response Phi = 0.443, P = 0.015. DISCUSSION AND CONCLUSION: The manual unloading test appears to be a reliable test and has a moderate to strong correlation with pain relief that exceeds minimal clinically important difference (MCID) following traction supporting the validity of this test. PMID- 27559275 TI - The influence of home exercise programs for patients with non-specific or specific neck pain: a systematic review of the literature. AB - STUDY DESIGN: Systematic review of randomized controlled trials (RCT). OBJECTIVES: To examine the effects of a therapeutic home exercise program (HEP) for patients with neck pain (associated with whiplash, non-specific, or specific neck pain, with or without radiculopathy, or cervicogenic headache) on pain, function, and disability. Our secondary aim was to describe the design, dosage, and adherence of the prescribed HEPs. BACKGROUND: Neck pain is a leading cause of disability that affects 22-70% of the population. Different techniques have been found effective for the treatment of neck pain. However, there is conflicting evidence to support the role of a therapeutic HEP to reduce pain, disability, and improve function and quality of life (QOL). METHODS: A systematic review in accordance with the preferred reporting items for systematic reviews and meta analyses (PRISMA) statement for reporting systematic reviews. The full-text review utilized the Maastricht-Amsterdam assessment tool to assess quality among RCTs. RESULTS: A total of 1927 subjects included within seven full-text articles met our specific search strategy. It was found that HEPs with a focus on strength and endurance-training exercises, as well as self- mobilization, have a positive effect when used in combination with other conservative treatments or alone. CONCLUSIONS: Home exercise programs that utilize either self-mobilizations within an augmented HEP to address specific spinal levels, or strengthening, and/or endurance exercise are effective at reducing neck pain, function, and disability and improving QOL. The benefit of HEPs in combination with other conservative interventions yields some benefit with a range of effect sizes. PMID- 27559276 TI - Utilization of mechanical diagnosis and therapy (MDT) for the treatment of lumbar pain in the presence of known lumbar transverse process fractures: a case study. AB - BACKGROUND: Spinal fractures are typically considered a contraindication to mechanical diagnosis and therapy (MDT). OBJECTIVE AND IMPORTANCE: The purpose of this case study is to illustrate how MDT was used safely and effectively to treat lumbar pain in a patient with multiple lumbar transverse process fractures. CLINICAL PRESENTATION: The subject was a 24-year-old female with left L2-5 transverse process fractures, sustained 10 weeks prior in a pedestrian versus motor vehicle accident. INTERVENTION AND TECHNIQUE: After collaboration with her physiatrist, an MDT examination revealed a presentation consistent with the lumbar derangement syndrome. CONCLUSION: After three visits, utilizing patient generated forces with the extension principle of treatment, her pain, Oswestry disability index (ODI) score, and function all improved. PMID- 27559277 TI - Medium term effects of including manual therapy in a pulmonary rehabilitation program for chronic obstructive pulmonary disease (COPD): a randomized controlled pilot trial. AB - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To investigate the effect of including manual therapy (MT) in a pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: The primary source of exercise limitation in people with COPD is dyspnea. The dyspnea is partly caused by changes in chest wall mechanics, with an increase in chest wall rigidity (CWR) contributing to a decrease in lung function. As MT is known to increase joint mobility, administering MT to people with COPD carries with it the potential to influence CWR and lung function. METHODS: Thirty-three participants with COPD, aged between 55 and 70 years (mean = 65.5+/-4 years), were randomly assigned to three groups: pulmonary rehabilitation (PR) only, soft tissue therapy (ST) and PR, and ST, spinal manipulative therapy (SM), and PR. Outcome measures including forced expiratory volume in the 1st second (FEV1), forced vital capacity (FVC), 6-minute walking test (6MWT), St. George's respiratory questionnaire (SGRQ), and the hospital anxiety and depression (HAD) scale were recorded at 0, 8, 16, and 24 weeks. RESULTS: There was a significant difference in FVC between the three groups at 24 weeks (P = 0.04). For the ST+SM+PR group versus PR only the increase was 0.40 l (CI: 0.02, 0.79; P = 0.03). No major or moderate adverse events (AE) were reported following the administration of 131 ST and 272 SM interventions. DISCUSSION: The increase in FVC is a unique finding. Although the underlying mechanisms responsible for this outcome are not yet understood, the most likely explanation is the synergistic effect resulting from the combination of interventions. These results support the call for a larger clinical trial in the use of MT for COPD. PMID- 27559278 TI - Cervicothoracic junction thrust manipulation in the multimodal management of a patient with temporomandibular disorder. AB - Temporomandibular disorder (TMD) is a common condition that can be difficult to manage in physical therapy. A number of interventions, such as manual therapy, therapeutic exercise, and patient education have typically been used in some combination. However, the evidence regarding thrust manipulation of not only the local but also adjacent segments is sparse. Specifically, the use of cervicothoracic (CT) junction thrust manipulation has not previously been described in the management of individuals with TMD. In this case report, CT junction thrust manipulation, in addition to locally directed manual therapy, exercise, and postural education, was associated with immediate improvements in neck and jaw symptoms and function in a complex patient with TMD. The patient was seen for seven visits over the course of 2 months and demonstrated clinically significant changes in the neck disability index (NDI), the numeric rating of pain scale (NPRS), and the global rating of change (GROC) scale. The purpose of this report is to describe the successful physical therapy management of a patient with TMD utilizing manual therapy, including CT junction thrust manipulation, education, and exercise. PMID- 27559279 TI - Inter-rater reliability of a modified version of Delitto et al.'s classification based system for low back pain: a pilot study. AB - STUDY DESIGN: Observational inter-rater reliability study. OBJECTIVES: To examine: (1) the inter-rater reliability of a modified version of Delitto et al.'s classification-based algorithm for patients with low back pain; (2) the influence of different levels of familiarity with the system; and (3) the inter rater reliability of algorithm decisions in patients who clearly fit into a subgroup (clear classifications) and those who do not (unclear classifications). METHODS: Patients were examined twice on the same day by two of three participating physical therapists with different levels of familiarity with the system. Patients were classified into one of four classification groups. Raters were blind to the others' classification decision. In order to quantify the inter rater reliability, percentages of agreement and Cohen's Kappa were calculated. RESULTS: A total of 36 patients were included (clear classification n = 23; unclear classification n = 13). The overall rate of agreement was 53% and the Kappa value was 0.34 [95% confidence interval (CI): 0.11-0.57], which indicated only fair inter-rater reliability. Inter-rater reliability for patients with a clear classification (agreement 52%, Kappa value 0.29) was not higher than for patients with an unclear classification (agreement 54%, Kappa value 0.33). Familiarity with the system (i.e. trained with written instructions and previous research experience with the algorithm) did not improve the inter-rater reliability. CONCLUSION: Our pilot study challenges the inter-rater reliability of the classification procedure in clinical practice. Therefore, more knowledge is needed about factors that affect the inter-rater reliability, in order to improve the clinical applicability of the classification scheme. PMID- 27559280 TI - Impact of shoulder internal rotation on ulnar nerve excursion and strain in embalmed cadavers. A pilot study. AB - DESIGN: Laboratory study, repeated-measures design. OBJECTIVE: To determine if the substitution of shoulder internal rotation for external rotation during the upper limb neurodynamic test (ULNT3) evokes a comparable ulnar nerve excursion and strain in embalmed cadavers. Shoulder external rotation is a primary movement component of the ULNT3. It has been suggested that shoulder internal rotation may provide a similar load to the nervous system. There are no data to either support or negate this claim. METHODS: Excursion and strain were measured in the ulnar nerve of six embalmed cadavers during the traditional ULNT3 and an experimental maneuver using shoulder internal rotation. RESULTS: The total means+/-SD of excursion for the traditional and experimental maneuvers were 2.11+/-0.89 and 2.09+/-0.92 mm, respectively. The total means+/-SD of strain for the traditional and experimental maneuvers were 5.274+/-2.223 and 5.241+/-2.308%, respectively. A very strong correlation (r = 0.98) was shown to exist between maneuvers and this relationship was determined to be significant (P = 0.001). DISCUSSION: The results of this study provide evidence that there is no appreciable difference in excursion or strain when substituting shoulder internal rotation for external rotation during the ULNT3. Patients who exhibit limitation of shoulder external rotation mobility may benefit from this substitution when presenting with signs of ulnar nerve pathodynamics. Further research involving patients will be needed to assess the validity of the experimental maneuver for clinical application. PMID- 27559281 TI - Should evidence or sound clinical reasoning dictate patient care? PMID- 27559282 TI - Strategies to overcome size and mechanical disadvantages in manual therapy. AB - The practice of manual therapy (MT) is often difficult when providing care for large patients and for practitioners small in stature or with other physical limitations. Many MT techniques can be modified using simple principles to require less exertion, permitting consistency with standards of practice even in the presence of physical challenges. Commonly used MT techniques are herein described and demonstrated with alternative preparatory and movement methods, which can also be adopted for use in other techniques. These alternative techniques and the procedures used to adapt them warrant discussion among practitioners and educators in order to implement care, consistent with the best treatment evidence for many common musculoskeletal (MSK) conditions. The inclusion in educational curricula and MT training programs is recommended to enrich skill development in physical therapists (PTs), spanning entry-level practitioners to those pursuing advanced manual skills. PMID- 27559283 TI - The immediate effects of soft tissue mobilization versus therapeutic ultrasound for patients with neck and arm pain with evidence of neural mechanosensitivity: a randomized clinical trial. AB - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To investigate the immediate effects of soft tissue mobilization (STM) versus therapeutic ultrasound (US) in patients with neck and arm pain who demonstrate neural mechanical sensitivity. BACKGROUND: While experts have suggested that individuals with neck and arm pain associated with neural tissue mechanical sensitivity may benefit from STM, there has been little research to investigate this hypothesis. METHODS: Twenty-three patients with neck and arm pain and a positive upper limb neurodynamic test (ULNT) were randomly assigned to receive STM or therapeutic US during a single session. Outcome measures were collected immediately before and after treatment, and at 2-4 day follow-up. Primary outcomes were the Global Rating of Change (GROC), range of motion (ROM) during the ULNT, and pain rating during the ULNT. Secondary measures included the Neck Disability Index (NDI), Patient-Specific Functional Scale (PSFS), Numeric Pain Rating Scale (NPRS), and active range of shoulder abduction motion combined with the wrist neutral or wrist extension. RESULTS: A greater proportion of patients in the STM group reported a significant improvement on the GROC immediately after treatment (P = 0.003, STM = 75%, US = 9%), and at 2-4 day follow-up (P = 0.027, STM = 58%, US = 9%). Patients who received STM demonstrated greater improvements in ROM during ULNT (P = 0.026), PSFS (P = 0.007), and shoulder active ROM combined with wrist extension (P = 0.028). Improvements in Numeric Pain Rating Scale and pain during the ULNT were observed only in the STM group. There was no difference between groups for the NDI or shoulder abduction ROM with wrist neutral. CONCLUSION: Patients with neck and arm pain demonstrated greater improvements in ULNT ROM, GROC, and PSFS, and pain following STM than after receiving therapeutic US. LEVEL OF EVIDENCE: Therapy, level 1b. PMID- 27559284 TI - A model for teaching and learning spinal thrust manipulation and its effect on participant confidence in technique performance. AB - BACKGROUND: Despite emerging evidence to support the use of high velocity thrust manipulation in the management of lumbar spinal conditions, utilization of thrust manipulation among clinicians remains relatively low. One reason for the underutilization of these procedures may be related to disparity in training in the performance of these techniques at the professional and post professional levels. PURPOSE: To assess the effect of using a new model of active learning on participant confidence in the performance of spinal thrust manipulation and the implications for its use in the professional and post-professional training of physical therapists. METHODS: A cohort of 15 DPT students in their final semester of entry-level professional training participated in an active training session emphasizing a sequential partial task practice (SPTP) strategy in which participants engaged in partial task practice over several repetitions with different partners. Participants' level of confidence in the performance of these techniques was determined through comparison of pre- and post-training session surveys and a post-session open-ended interview. RESULTS: The increase in scores across all items of the individual pre- and post-session surveys suggests that this model was effective in changing overall participant perception regarding the effectiveness and safety of these techniques and in increasing student confidence in their performance. Interviews revealed that participants greatly preferred the SPTP strategy, which enhanced their confidence in technique performance. CONCLUSION: Results indicate that this new model of psychomotor training may be effective at improving confidence in the performance of spinal thrust manipulation and, subsequently, may be useful for encouraging the future use of these techniques in the care of individuals with impairments of the spine. Inasmuch, this method of instruction may be useful for training of physical therapists at both the professional and post-professional levels. PMID- 27559285 TI - Upper cervical instability associated with rheumatoid arthritis: a case report. AB - Rheumatoid arthritis (RA) affects between 1 and 2 million individuals in the United States. Atlantoaxial instability (AAI) has been shown to have 40-85% prevalence among individuals with RA. Despite the high incidence of craniovertebral involvement, overt symptoms of instability are rare. The high risk of AAI and limited symptomology should increase therapist suspicion of potential contraindications and precautions to initiation of therapy for the cervical spine without prior diagnostic imaging. The purpose of this case study is to describe the historical, clinical, and diagnostic imaging complexity of AAI associated with RA, and to illustrate the use of these factors in the clinical reasoning within a patient case. PMID- 27559286 TI - The application of mechanical diagnosis and therapy in lateral epicondylalgia. AB - BACKGROUND: lateral epicondylalgia (LE) is a musculoskeletal diagnosis that causes pain and dysfunction in the lateral aspect of the elbow. Mechanical diagnosis and therapy (MDT) is an orthopaedic classification and treatment system based on mechanical and symptomatic response to repeated and sustained end-range movement. There has been no investigation of the association between MDT and patients diagnosed with LE. CASE DESCRIPTION: this report presents three patients matching the currently accepted diagnostic criteria for LE, two with a diagnosis of lateral epicondylitis (tennis elbow) from a medical doctor. These patients were classified and treated by a diplomat of MDT and two third-year doctoral students of physical therapy using MDT. OUTCOMES: short- and long-term (one year) outcomes were excellent, demonstrating rapid abolishment of symptoms and return to prior levels of function in 3-6 visits between 11-59 days. Patients demonstrated the ability to prevent and manage reoccurrence of symptoms independently without seeking further health care. DISCUSSION: this case series raises questions about whether or not the pathologies traditionally associated with the aetiology of LE are actually at fault. Moreover, it raises questions about the utility of special tests typically utilized to identify those structures. The series provides preliminary evidence that MDT may be capable of providing effective short- and long-term outcomes in the management of LE. LEVEL OF EVIDENCE: 4. PMID- 27559287 TI - Factors affecting confidence and knowledge in spinal palpation among International Manual Physical Therapists. AB - OBJECTIVES: We sought to find if there was a relationship between the confidence in use of static palpation, passive physiological intervertebral motion (PPIVM) and passive accessory intervertebral motion (PAIVM) and the manual therapist's (MTs) knowledge of the literature on these topics. METHODS: We designed an international survey to achieve our objectives. Each skill was surveyed for the cervical, thoracic and lumbar spines. We also included several other factors that we believed might influence the use of these skills. RESULTS: We concluded that familiarity of the literature was significantly associated with a MTs' confidence in the use of static palpation, PPIVM and PAIVM techniques. We also found a relationship with the country of practice of the MT and their confidence using these techniques. DISCUSSION: Spinal palpation is an integral part of the MT's evaluation and treatment abilities. The vast majority of MTs use spinal palpation and nearly all entry-level education programmes include it in their training. Knowing what factors influence MTs' confidence assessing and treating the spine may allow for more effective teaching and training, as well as improved patient outcomes. PMID- 27559288 TI - The reliability and validity of the Saliba Postural Classification System. AB - OBJECTIVES: To determine the reliability and validity of the Saliba Postural Classification System (SPCS). METHODS: Two physical therapists classified pictures of 100 volunteer participants standing in their habitual posture for inter and intra-tester reliability. For validity, 54 participants stood on a force plate in a habitual and a corrected posture, while a vertical force was applied through the shoulders until the clinician felt a postural give. Data were extracted at the time the give was felt and at a time in the corrected posture that matched the peak vertical ground reaction force (VGRF) in the habitual posture. RESULTS: Inter-tester reliability demonstrated 75% agreement with a Kappa = 0.64 (95% CI = 0.524-0.756, SE = 0.059). Intra-tester reliability demonstrated 87% agreement with a Kappa = 0.8, (95% CI = 0.702-0.898, SE = 0.05) and 80% agreement with a Kappa = 0.706, (95% CI = 0.594-0818, SE = 0.057). The examiner applied a significantly higher (p < 0.001) peak vertical force in the corrected posture prior to a postural give when compared to the habitual posture. Within the corrected posture, the %VGRF was higher when the test was ongoing vs. when a postural give was felt (p < 0.001). The %VGRF was not different between the two postures when comparing the peaks (p = 0.214). DISCUSSION: The SPCS has substantial agreement for inter- and intra-tester reliability and is largely a valid postural classification system as determined by the larger vertical forces in the corrected postures. Further studies on the correlation between the SPCS and diagnostic classifications are indicated. PMID- 27559290 TI - Neutrophil extracellular traps involvement in corneal fungal infection. AB - PURPOSE: Neutrophils release neutrophil extracellular traps (NETs) when defending against invading microorganisms. We investigated the existence of NETs in fungal keratitis. METHODS: Fourteen patients with unilateral fungal keratitis were included. Detailed information about each patient was recorded, including (1) patient history (onset of symptoms and previous therapy), (2) ocular examination findings by slit-lamp biomicroscopy, (3) laboratory findings from direct smear examination and culture of corneal scrapings, (4) NET formation, and (5) treatment strategy and prognosis. Immunofluorescence staining was used to evaluate the existence of NETs on corneal scrapings. The relationship between the quantification of NETs and the clinical character of the fungal keratitis was identified. RESULTS: NETs were identified in all 14 patients. Patients with a higher grade of NET formation and fewer fungal hyphae always showed a good treatment response and a short course of infection. NETs were consistently found mixed with fungal hyphae in the corneal scrapings from infected patients. No statistical significance was found between the grade of NETs formed and the course of infection before presentation, and no relationship between the quantification of NETs and the size of the ulcer was found. CONCLUSIONS: The results suggest that NETs are involved in fungal keratitis. The number of NETs in infected corneas may provide a tool for evaluating the prognosis for fungal keratitis. PMID- 27559289 TI - Quantitative proteomics analysis with iTRAQ in human lenses with nuclear cataracts of different axial lengths. AB - PURPOSE: The goal of this study was to identify and quantify the differentially expressed proteins in human nuclear cataract with different axial lengths. METHODS: Thirty-six samples of human lens nuclei with hardness grade III or IV were obtained during cataract surgery with extracapsular cataract extraction (ECCE). Six healthy transparent human lens nuclei were obtained from fresh healthy cadaver eyes during corneal transplantation surgery. The lens nuclei were divided into seven groups (six lenses in each group) according to the optic axis: Group A (mean axial length 28.7+/-1.5 mm; average age 59.8+/-1.9 years), Group B (mean axial length 23.0+/-0.4 mm; average age 60.3+/-2.5 years), Group C (mean axial length 19.9+/-0.5 mm; average age 55.1+/-2.5 years), Group D (mean axial length 28.7+/-1.4 mm; average age 58.0+/-4.0 years), Group E (mean axial length 23.0+/-0.3 mm; average age 56.9+/-4.2 years), and Group F (mean axial length 20.7+/-0.6 mm; average age 57.6+/-5.3 years). The six healthy transparent human lenses were included in a younger group with standard optic axes, Group G (mean axial length 23.0+/-0.5 mm; average age 34.7+/-4.2 years).Water-soluble, water insoluble, and water-insoluble-urea-soluble protein fractions were extracted from the samples. The three-part protein fractions from the individual lenses were combined to form the total proteins of each sample. The proteomic profiles of each group were analyzed using 8-plex isobaric tagging for relative and absolute protein quantification (iTRAQ) labeling combined with two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS). The data were analyzed with ProteinPilot software for peptide matching, protein identification, and quantification. Differentially expressed proteins were validated with western blotting. RESULTS: We employed biological and technical replicates and selected the intersection of the two sets of results, which included 40 proteins. From the 40 proteins identified, six were selected as differentially expressed proteins closely related to axial length. The six proteins were gap junction alpha-3 protein, beta-crystallin B2, T-complex protein 1 subunit beta, gamma-enolase, pyruvate kinase isozymes M1/M2, and sorbitol dehydrogenase. Levels of beta crystallin B2 expression were decreased in nuclear cataracts with longer axial length. The results of the mass spectrometric analysis were consistent with the western blot validation. CONCLUSION: The discovery of these differentially expressed proteins provides valuable clues for understanding the pathogenesis of axial-related nuclear cataract. The results indicate that beta-crystallin B2 (CRBB2) may be involved in axial-related nuclear cataract pathogenesis. Further studies are needed to investigate the correlation between CRBB2 and axial-related nuclear cataract. PMID- 27559291 TI - Technical brief: Pump-probe paradigm in an integrating cavity to study photodecomposition processes. AB - PURPOSE: Assaying photodecomposition is challenging because light must be used to initiate the photodamage and light must be used to monitor the photodecomposition. The experimental requirements are as follows: 1) During exposure of the actinic beam, continuously monitor the spectral characteristics of the sample, 2) uniformly expose the reactants to the actinic source, 3) obtain informative spectra in the presence of light scatter, and 4) achieve sufficient sensitivity for dilute reactants. Traditional spectrophotometers cannot address these issues due to sample turbidity, the inability to uniformly expose the cuvette contents to the incident beam, the inability to simultaneously perform spectral scans, and inherent low sensitivity. Here, we describe a system that meets these challenges in a practical way. METHODS: Light access to a 8.6 ml quartz integrating sphere containing 10 uM all-trans retinol in PBS was provided by three ports at right angles allowing for the following: 1) actinic light delivery from light-emitting diodes (LEDs) firing at 100 pulses/sec, 2) entry of a separate scanning beam at 100 scans/sec (10,000 usec scan time) via an OLIS RSM 1000 ultraviolet/visual (UV/Vis) rapid-scanning spectrophotometer (RSM), and 3) light exit to the detector photomultiplier. The RSM spectral intermediate slit was partially covered to allow for a "dark" period of 2,000 usec when no scanning light was admitted to the cuvette. During that interval, the LED was flashed, and the photomultiplier was temporarily blocked by a perforated spinning shutter disk. The absorbance per centimeter, which is increased due to the internal reflectance of the integrating sphere compared to a standard 1 cm rectangular cuvette, was calculated according to Fry et al. (2010) Applied Optics 49:575. Retinoid photodecomposition was confirmed with high-performance liquid chromatography (HPLC). RESULTS: Using the RSM to trigger the LED flash and photomultiplier shutter closure during the "dark" period allowed actinic flashes to be placed between scans. Exposure of the all-trans retinol to 366 nm flashes resulted in marked reduction in absorbance and a blue shift of the lambdamax. A white LED, despite its higher photon output, did not support all-trans retinol photolysis. Singular value decomposition (SVD) analysis revealed three spectral intermediates with mechanism, I -> II -> III. HPLC analysis of the reactants at the beginning and the conclusion of the light exposure confirmed the retinol photodecomposition. CONCLUSIONS: The highly reflecting cavity acts as a multipass cuvette that markedly increased the light path length and, thus, sensitivity. Triggering the LED during a dark period within the scan time allowed the actinic flashes to be interleafed between scans in a pump-probe paradigm. Furthermore, the entire sample was exposed to scan beam and actinic flashes, which is not possible in traditional spectrophotometers. Finally, the integrating cavity cuvette allowed use of turbid samples. SVD was useful for resolving spectral intermediates. Although the identity of the intermediates was not determined here, the ability to define molecular intermediates during photodecomposition reactions will allow future studies to isolate and identify the degradation products and determine the mechanism of light-induced retinoid degradation and that of retinoid-binding protein-mediated photoprotection. PMID- 27559292 TI - Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina. AB - PURPOSE: Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock. METHODS: To quantify circadian expression of clock and clock-controlled genes, retinas and suprachiasmatic nucleus (SCN) from the same animals were collected every 4 h in circadian conditions, 12 weeks post-diabetes. Induction of Per1, Per2, and c-fos mRNAs was quantified in the retina after the administration of a pulse of monochromatic light (480 nm, 1.17*10(14) photons/cm(2)/s, 15 min) at circadian time 16. Gene expression was assessed with real-time reverse transcription PCR (RT-PCR). Pooled retinas from the control and STZ-diabetic mice were collected 2 h after light ON and light OFF (Zeitgeber time (ZT)2 and ZT14), and DA and its metabolite were analyzed with high-performance liquid chromatography (HPLC). RESULTS: We found variable effects of diabetes on the expression of clock genes in the retina and only slight differences in phase and/or amplitude in the SCN. c fos and Per1 induction by a 480 nm light pulse was abolished in diabetic animals at 12 weeks post-induction of diabetes in comparison with the control mice, suggesting a deficit in light-induced neuronal activation of the retinal clock. Finally, we quantified a 56% reduction in the total number of tyrosine hydroxylase (TH) immunopositive cells, associated with a decrease in DA levels during the subjective day (ZT2). CONCLUSIONS: These findings demonstrate that diabetes affects the molecular machinery and the light response of the retinal clock and alters the light-driven retinal DA level. PMID- 27559294 TI - Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map. AB - We performed gene expression microarray analysis coupled with spherical self organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs. PMID- 27559293 TI - Expression of the type VI intermediate filament proteins CP49 and filensin in the mouse lens epithelium. AB - PURPOSE: The differentiated lens fiber cell assembles a filamentous cytoskeletal structure referred to as the beaded filament (BF). The BF requires CP49 (bfsp2) and filensin (bfsp1) for assembly, both of which are highly divergent members of the large intermediate filament (IF) family of proteins. Thus far, these two proteins have been reported only in the differentiated lens fiber cell. For this reason, both proteins have been considered robust markers of fiber cell differentiation. We report here that both proteins are also expressed in the mouse lens epithelium, but only after 5 weeks of age. METHODS: Localization of CP49 was achieved with immunocytochemical probing of wild-type, CP49 knockout, filensin knockout, and vimentin knockout mice, in sections and in the explanted lens epithelium, at the light microscope and electron microscope levels. The relationship between CP49 and other cytoskeletal elements was probed using fluorescent phalloidin, as well as with antibodies to vimentin, GFAP, and alpha tubulin. The relationship between CP49 and the aggresome was probed with antibodies to gamma-tubulin, ubiquitin, and HDAC6. RESULTS: CP49 and filensin were expressed in the mouse lens epithelium, but only after 5 weeks of age. At the light microscope level, these two proteins colocalize to a large tubular structure, approximately 7 * 1 MUm, which was typically present at one to two copies per cell. This structure is found in the anterior and anterolateral lens epithelium, including the zone where mitosis occurs. The structure becomes smaller and largely undetectable closer to the equator where the cell exits the cell cycle and commits to fiber cell differentiation. This structure bears some resemblance to the aggresome and is reactive with antibodies to HDAC6, a marker for the aggresome. However, the structure does not colocalize with antibodies to gamma-tubulin or ubiquitin, also markers for the aggresome. The structure also colocalizes with actin but appears to largely exclude vimentin and alpha-tubulin. In the CP49 and filensin knockouts, this structure is absent, confirming the identity of CP49 and filensin in this structure, and suggesting a requirement for the physiologic coassembly of CP49 and filensin. CONCLUSIONS: CP49 and filensin have been considered robust markers for mouse lens fiber cell differentiation. The data reported here, however, document both proteins in the mouse lens epithelium, but only after 5 weeks of age, when lens epithelial growth and mitotic activity have slowed. Because of this, CP49 and filensin must be considered markers of differentiation for both fiber cells and the lens epithelium in the mouse. In addition, to our knowledge, no other protein has been shown to emerge so late in the development of the mouse lens epithelium, suggesting that lens epithelial differentiation may continue well into post-natal life. If this structure is related to the aggresome, it is a rare, or perhaps unique example of a large, stable aggresome in wild-type tissue. PMID- 27559295 TI - In Silico Structure Prediction of Human Fatty Acid Synthase-Dehydratase: A Plausible Model for Understanding Active Site Interactions. AB - Fatty acid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as beta-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, beta-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate beta-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate-active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro. PMID- 27559296 TI - Autism Spectrum Disorder and Co-occurring Substance Use Disorder - A Systematic Review. AB - OBJECTIVE: Patients with co-occurring autism spectrum disorders (ASD) and substance use disorder (SUD) require special attention from clinical services. Screening for this co-occurrence is not generally an integral part of routine clinical assessments, and failure to identify and understand this group of patients may contribute to a worsening of their symptoms and/or an increase in drug abuse. Thus, there is a need to review the evidence base on patients with co occurring ASD and SUD in order to enhance clinical practice and future research. METHODS: We reviewed all identified papers on patients with co-occurring ASD and SUD. The focus of the review was on epidemiology, patient characteristics, function of drug use, and the effect of current interventions. RESULTS: A total of 18 papers were included in the analysis. Eleven papers were based on epidemiological studies, although only one study reported the prevalence of ASD in an SUD population. Two papers explored the role of personality, three papers studied subgroups of individuals serving prison for violent or sexual crimes, and one paper explored the function of drugs in the ASD patient group. There were no studies testing specific treatment interventions. CONCLUSIONS: In most of the treatment settings studied, there were relatively few patients with co-occurring ASD and SUD, but due to differences in study samples it was difficult to establish a general prevalence rate. The one consistent finding was the lack of focused treatment studies. There is clearly a need for research on interventions that take account of the special needs of this patient group. PMID- 27559299 TI - Grape Seed Oil Compounds: Biological and Chemical Actions for Health. AB - Grape seed oil is rich in phenolic compounds, fatty acids, and vitamins, with economic importance to pharmaceutical, cosmetic, and food industry. Its use as an edible oil has also been suggested, especially due to its pleasant sensory characteristics. Grape seed oil has beneficial properties for health that are mainly detected by in vitro studies, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, and may interact with cellular and molecular pathways. These effects have been related to grape seed oil constituents, mainly tocopherol, linolenic acid, resveratrol, quercetin, procyanidins, carotenoids, and phytosterols. The aim of this article was to briefly review the composition and nutritional aspects of grape seed oil, the interactions of its compounds with molecular and cellular pathways, and its possible beneficial effects on health. PMID- 27559298 TI - Role of Aryl Hydrocarbon Receptor in Circadian Clock Disruption and Metabolic Dysfunction. AB - The prevalence of metabolic syndrome, a clustering of three or more risk factors that include abdominal obesity, increased blood pressure, and high levels of glucose, triglycerides, and high-density lipoproteins, has reached dangerous and costly levels worldwide. Increases in morbidity and mortality result from a combination of factors that promote altered glucose metabolism, insulin resistance, and metabolic dysfunction. Although diet and exercise are commonly touted as important determinants in the development of metabolic dysfunction, other environmental factors, including circadian clock disruption and activation of the aryl hydrocarbon receptor (AhR) by dietary or other environmental sources, must also be considered. AhR binds a range of ligands, which prompts protein protein interactions with other Per-Arnt-Sim (PAS)-domain-containing proteins and subsequent transcriptional activity. This review focuses on the reciprocal crosstalk between the activated AhR and the molecular circadian clock. AhR exhibits a rhythmic expression and time-dependent sensitivity to activation by AhR agonists. Conversely, AhR activation influences the amplitude and phase of expression of circadian clock genes, hormones, and the behavioral responses of the clock system to changes in environmental illumination. Both the clock and AhR status and activation play significant and underappreciated roles in metabolic homeostasis. This review highlights the state of knowledge regarding how AhR may act together with the circadian clock to influence energy metabolism. Understanding the variety of AhR-dependent mechanisms, including its interactions with the circadian timing system that promote metabolic dysfunction, reveals new targets of interest for maintenance of healthy metabolism. PMID- 27559300 TI - Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas. AB - Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-((18)F)fluoro-d-glucose ((18)F-FDG) PET/CT and full dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary. PMID- 27559301 TI - Disseminated Mycobacterium bovis Infection Complicating Intravesical BCG Instillation for the Treatment of Superficial Transitional Cell Carcinoma of the Bladder. AB - BACKGROUND: Intravesical instillation of Bacillus Calmette-Guerin (BCG) remains a first-line treatment for superficial transitional cell carcinoma of the bladder. Although its use is relatively safe, severe complications such as granulomatous hepatitis, osteomyelitis, pneumonitis, and sepsis occur in few patients. Complications of intravesical instillation of BCG can be local or systemic, with early or late presentation. CASE PRESENTATION: Here, we report an 88-year-old man who developed fever, rigors, and episodes of syncope following fourth intravesical BCG instillation for the treatment of superficial transitional cell carcinoma of the bladder. Pancytopenia, disseminated intravascular coagulation, ground glass appearance on computerized tomography of the chest scan in addition to multiple bone marrow granulomas, suggested the diagnosis of disseminated BCG infection. All these features recovered on antituberculosis treatment. CONCLUSION: Our case study highlights the importance of early recognition and prompt treatment of patients with disseminated BCG infection following intravesical instillation. Although isolation of mycobacterium is desirable to make the diagnosis, it is not unusual to have negative smears and cultures and this should not be used to dismiss the possibility of BCG infection. PMID- 27559297 TI - Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer. AB - Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. PMID- 27559302 TI - Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. AB - INTRODUCTION: Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS: This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comte region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m(2) per day, followed by six cycles of maintenance temozolomide (150-200 mg/m(2), five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS: One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5-15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3-4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS: This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3-4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients. PMID- 27559303 TI - Generic revision of the ant subfamily Dorylinae (Hymenoptera, Formicidae). AB - The generic classification of the ant subfamily Dorylinae is revised, with the aim of facilitating identification of easily-diagnosable monophyletic genera. The new classification is based on recent molecular phylogenetic evidence and a critical reappraisal of doryline morphology. New keys and diagnoses based on workers and males are provided, along with reviews of natural history and phylogenetic relationships, distribution maps, and a list of valid species for each lineage. Twenty-eight genera (27 extant and 1 extinct) are recognized within the subfamily, an increase from 20 in the previous classification scheme. Species classified in the polyphyletic Cerapachys and Sphinctomyrmex prior to this publication are here distributed among 9 and 3 different genera, respectively. Amyrmex and Asphinctanilloides are synonymized under Leptanilloides and the currently recognized subgenera are synonymized for Dorylus. No tribal classification is proposed for the subfamily, but several apparently monophyletic genus-groups are discussed. Valid generic names recognized here include: Acanthostichus (= Ctenopyga), Aenictogiton, Aenictus (= Paraenictus, Typhlatta), Cerapachys (= Ceratopachys), Cheliomyrmex, Chrysapace gen. rev., Cylindromyrmex (= Holcoponera, Hypocylindromyrmex, Metacylindromyrmex), Dorylus (= Alaopone syn. n., Anomma syn. n., Cosmaecetes, Dichthadia syn. n., Rhogmus syn. n., Shuckardia, Sphecomyrmex, Sphegomyrmex, Typhlopone syn. n.), Eburopone gen. n., Eciton (= Camptognatha, Holopone, Mayromyrmex), Eusphinctus gen. rev., Labidus (= Nycteresia, Pseudodichthadia), Leptanilloides (= Amyrmex syn. n., Asphinctanilloides syn. n.), Lioponera gen. rev. (= Neophyracaces syn. n., Phyracaces syn. n.), Lividopone, Neivamyrmex (= Acamatus, Woitkowskia), Neocerapachys gen. n., Nomamyrmex, Ooceraea gen. rev. (= Cysias syn. n.), Parasyscia gen. rev., ?Procerapachys, Simopone, Sphinctomyrmex, Syscia gen. rev., Tanipone, Vicinopone, Yunodorylus gen. rev., Zasphinctus gen. rev. (= Aethiopopone syn. n., Nothosphinctus syn. n.). PMID- 27559304 TI - The winds from HL Tau. AB - Outflowing motions, whether a wind launched from the disc, a jet launched from the protostar, or the entrained molecular outflow, appear to be a ubiquitous feature of star formation. These outwards motions have a number of root causes, and how they manifest is intricately linked to their environment as well as the process of star formation itself. Using the Atacama Large Millimeter/submillimeter Array (ALMA) Science Verification data of HL Tau, we investigate the high-velocity molecular gas being removed from the system as a result of the star formation process. We aim to place these motions in context with the optically detected jet, and the disc. With these high-resolution (~1 arcsec) ALMA observations of CO (J=1-0), we quantify the outwards motions of the molecular gas. We find evidence for a bipolar outwards flow, with an opening angle, as measured in the redshifted lobe, starting off at 90 degrees , and narrowing to 60 degrees further from the disc, likely because of magnetic collimation. Its outwards velocity, corrected for inclination angle is of the order of 2.4 km s-1. PMID- 27559305 TI - Imaginative Language: What Event-Related Potentials have Revealed about the Nature and Source of Concreteness Effects. AB - Behavioral and neuropsychological evidence suggest that abstract and concrete concepts may be represented, retrieved, and processed differently in the human brain. As reviewed in this paper, data using event-related potential measures, some in combination with visual half-field presentation methods, have offered a detailed picture of the nature and source of concreteness effects. In particular, the results provide strong evidence for multiple mechanisms underlying the behavioral processing differences that have long been noted for concrete and abstract words and, further, suggest an intriguing, unique role for the right hemisphere in associating words with sensory imagery. PMID- 27559306 TI - Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation. AB - The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID- 27559307 TI - Synaptic GluN2B/CaMKII-alpha Signaling Induces Synapto-Nuclear Transport of ERK and Jacob. AB - A central pathway in synaptic plasticity couples N-Methyl-D-Aspartate-receptor (NMDAR)-signaling to the activation of extracellular signal-regulated kinases (ERKs) cascade. ERK-dependency has been demonstrated for several forms of synaptic plasticity as well as learning and memory and includes local synaptic processes but also long-distance signaling to the nucleus. It is, however, controversial how NMDAR signals are connected to ERK activation in dendritic spines and nuclear import of ERK. The synapto-nuclear messenger Jacob couples NMDAR-dependent Ca(2+)-signaling to CREB-mediated gene expression. Protein transport of Jacob from synapse to nucleus essentially requires activation of GluN2B-containing NMDARs. Subsequent phosphorylation and binding of ERK1/2 to and ERK-dependent phosphorylation of serine 180 in Jacob encodes synaptic but not extrasynaptic NMDAR activation. In this study we show that stimulation of synaptic NMDAR in hippocampal primary neurons and induction of long-term potentiation (LTP) in acute slices results in GluN2B-dependent activation of CaMKII-alpha and subsequent nuclear import of active ERK and serine 180 phosphorylated Jacob. On the contrary, no evidence was found that either GluN2A containing NMDAR or RasGRF2 are upstream of ERK activation and nuclear import of Jacob and ERK. PMID- 27559308 TI - LGR4 and LGR5 Regulate Hair Cell Differentiation in the Sensory Epithelium of the Developing Mouse Cochlea. AB - In the developing cochlea, Wnt/beta-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/beta-catenin activity in the cochlea. In multiple tissues, the activity of Wnt/beta-catenin signaling is modulated by an interaction between LGR receptors and their ligands from the R-spondin family. The deficiency in Lgr4 and Lgr5 genes leads to developmental malformations and lethality. Using the Lgr5 knock-in mouse line we show that loss of LGR5 function increases Wnt/beta-catenin activity in the embryonic cochlea, resulting in a mild overproduction of inner and outer hair cells (OHC). Supernumerary hair cells are likely formed due to an up regulation of the "pro-hair cell" transcription factors Atoh1, Nhlh1, and Pou4f3. Using a hypomorphic Lgr4 mouse model we showed a mild overproduction of OHCs in the heterozygous and homozygous Lgr4 mice. The loss of LGR4 function prolonged the proliferation in the mid-basal turn of E13 cochleae, causing an increase in the number of SOX2-positive precursor cells within the pro-sensory domain. The premature differentiation of hair cells progressed in a medial to lateral gradient in Lgr4 deficient embryos. No significant up-regulation of Atoh1 was observed following Lgr4 deletion. Altogether, our findings suggest that LGR4 and LGR5 play an important role in the regulation of hair cell differentiation in the embryonic cochlea. PMID- 27559309 TI - Tonotopic and Field-Specific Representation of Long-Lasting Sustained Activity in Rat Auditory Cortex. AB - Cortical information processing of the onset, offset, and continuous plateau of an acoustic stimulus should play an important role in acoustic object perception. To date, transient activities responding to the onset and offset of a sound have been well investigated and cortical subfields and topographic representation in these subfields, such as place code of sound frequency, have been well characterized. However, whether these cortical subfields with tonotopic representation are inherited in the sustained activities that follow transient activities and persist during the presentation of a long-lasting stimulus remains unknown, because sustained activities do not exhibit distinct, reproducible, and time-locked responses in their amplitude to be characterized by grand averaging. To address this gap in understanding, we attempted to decode sound information from densely mapped sustained activities in the rat auditory cortex using a sparse parameter estimation method called sparse logistic regression (SLR), and investigated whether and how these activities represent sound information. A microelectrode array with a grid of 10 * 10 recording sites within an area of 4.0 mm * 4.0 mm was implanted in the fourth layer of the auditory cortex in rats under isoflurane anesthesia. Sustained activities in response to long-lasting constant pure tones were recorded. SLR then was applied to discriminate the sound induced band-specific power or phase-locking value from those of spontaneous activities. The highest decoding performance was achieved in the high-gamma band, indicating that cortical inhibitory interneurons may contribute to the sparse tonotopic representation in sustained activities by mediating synchronous activities. The estimated parameter in the SLR decoding revealed that the informative recording site had a characteristic frequency close to the test frequency. In addition, decoding of the four test frequencies demonstrated that the decoding performance of the SLR deteriorated when the test frequencies were close, supporting the hypothesis that the sustained activities were organized in a tonotopic manner. Finally, unlike transient activities, sustained activities were more informative in the belt than in the core region, indicating that higher order auditory areas predominate over lower-order areas during sustained activities. Taken together, our results indicate that the auditory cortex processes sound information tonotopically and in a hierarchical manner. PMID- 27559311 TI - Disentangling Rheumatoid Arthritis Patients' Implicit and Explicit Attitudes toward Methotrexate. AB - Medication non-adherence is a major public health problem that has been termed an 'invisible epidemic.' Non-adherence is not only associated with negative clinical consequences but can also result in substantial healthcare costs. Up to now, effective adherence interventions are scarce and a more comprehensive model of adherence determinants is required to target the determinants for not taking the medication as prescribed. Current approaches only included explicit attitudes such as self-reported evaluations of medication as determinants, neglecting the role of associative processes that shape implicit attitudes. Implicit processes can predict daily behavior more accurately than explicit attitudes. Our aim is to assess explicit and implicit attitudes toward medication and explore the relation with beliefs, adherence and clinical (laboratory) outcomes in chronically ill patients. Fifty two Rheumatic Arthritis (RA) patients' attitudes toward Methotrexate (MTX) were explicitly (self-reported) and implicitly (Single Category Implicit Association Test) assessed and related to the Beliefs about Medicine Questionnaire, the Compliance Questionnaire on Rheumatology and laboratory parameters [Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP)]. Results show that explicit attitudes were positive and health-related. Implicit attitudes were, however, negative and sickness-related. Half of the patients displayed explicitly positive but implicitly negative attitudes. Explicit attitudes were positively related to ESR. A positive relationship between implicit attitudes and disease duration was observed. In this study, we have obtained evidence suggesting that the measurement of implicit attitudes and associations provides different information than explicit, self-reported attitudes toward medication. Since patients' implicit attitudes deviated from explicit attitudes, we can conclude that the relationship between implicit attitudes and medication adherence is worthwhile to be further explored. With this information we can improve our understanding of the subconscious, automatic processes underlying adherence and we can develop interventions that target these implicit attitudes. PMID- 27559312 TI - Assessment of Potential Herb-Drug Interactions among Nigerian Adults with Type-2 Diabetes. AB - It is becoming increasingly evident that patients with diabetes do not rely only on prescription drugs for their disease management. The use of herbal medicines is one of the self-management practices adopted by these patients, often without the knowledge of their healthcare practitioners. This study assessed the potential for pharmacokinetic herb-drug interactions (HDIs) amongst Nigerian adult diabetic patients. This was done through a literature analysis of the pharmacokinetic profile of their herbal medicines and prescription drugs, based on information obtained from 112 patients with type-2 diabetes attending two secondary health care facilities in Nigeria. Fifty percent of the informants used herbal medicines alongside their prescription drugs. Worryingly, 60% of the patients taking herbal medicines did not know their identity, thus increasing the risk of unidentified HDIs. By comparing the pharmacokinetic profile of eight identified herbs taken by the patients for the management of diabetes against those of the prescription drugs, several scenarios of potential HDIs were identified and their clinical relevance is discussed. The lack of clinical predictors points toward cultural factors as the influence for herb use, making it more difficult to identify these patients and in turn monitor potential HDIs. In identifying these possible interactions, we have highlighted the need for healthcare professionals to promote a proactive monitoring of patients' use of herbal medicines. PMID- 27559310 TI - Peripheral Sensory Neurons Expressing Melanopsin Respond to Light. AB - The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Adelta fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior. PMID- 27559313 TI - A Novel Agent Enhances the Chemotherapeutic Efficacy of Doxorubicin in MCF-7 Breast Cancer Cells. AB - We have previously demonstrated that DT-010, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), displays anti-tumor effects in breast cancer cells both in vitro and in vivo. In the present study, we investigated whether DT-010 enhances the chemotherapeutic effect of doxorubicin (Dox) in MCF-7 breast cancer cells and exerts concurrent cardioprotective benefit at the same time. Our findings showed that DT-010 was more potent than TMP, DSS, or their combination in potentiating Dox-induced toxicity in MCF-7 cells. Co-treatment with DT-010 and Dox increased apoptosis in MCF-7 cells relative to Dox alone. Further study indicated that glycolytic capacity, glycolytic reserve and lactate level of MCF-7 cells were significantly inhibited after DT-010 treatment. DT-010 also increased the expression of the pro-survival protein GRP78, which was inhibited by co treatment with Dox. Both endoplasmic reticulum stress inhibitor 4-PBA and knockdown of the expression of GRP78 protein potentiated DT-010-mediated apoptosis in MCF-7 cells. Moreover, DT-010 inhibited Dox-induced cardiotoxicity in H9c2 myoblasts. In conclusion, DT-010 and Dox confer synergistic anti-tumor effect in MCF-7 breast cancer cells through downregulation of the glycolytic pathway and inhibition of the expression of GRP78. Meanwhile, DT-010 also protects against Dox-induced cardiotoxicity. PMID- 27559314 TI - Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice. AB - The precision-cut lung slice (PCLS) is a powerful tool for studying airway reactivity, but biomechanical measurements to date have largely focused on changes in airway caliber. Here we describe an image processing tool that reveals the associated spatio-temporal changes in airway and parenchymal strains. Displacements of sub-regions within the PCLS are tracked in phase-contrast movies acquired after addition of contractile and relaxing drugs. From displacement maps, strains are determined across the entire PCLS or along user-specified directions. In a representative mouse PCLS challenged with 10(-4)M methacholine, as lumen area decreased, compressive circumferential strains were highest in the 50 MUm closest to the airway lumen while expansive radial strains were highest in the region 50-100 MUm from the lumen. However, at any given distance from the airway the strain distribution varied substantially in the vicinity of neighboring small airways and blood vessels. Upon challenge with the relaxant agonist chloroquine, although most strains disappeared, residual positive strains remained a long time after addition of chloroquine, predominantly in the radial direction. Taken together, these findings establish strain mapping as a new tool to elucidate local dynamic mechanical events within the constricting airway and its supporting parenchyma. PMID- 27559315 TI - Impaired Exercise Performance and Skeletal Muscle Mitochondrial Function in Rats with Secondary Carnitine Deficiency. AB - PURPOSE: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP), a carnitine analog inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats. METHODS: Male Sprague Dawley rats were treated daily with water (control rats; n = 12) or with 20 mg/100 g body weight THP (n = 12) via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion. RESULTS: Distance covered and exercise performance were lower in THP treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24%) and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption) was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected. CONCLUSIONS: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle. PMID- 27559316 TI - Cerebro- and Cardio-vascular Responses to Energy Drink in Young Adults: Is there a Gender Effect? AB - BACKGROUND AND PURPOSE: Energy drinks (EDs) are suspected to induce potential adverse cardiovascular effects and have recently been shown to reduce cerebral blood flow velocity (CBFV) in young, healthy subjects. Gender differences in CBFV in response to EDs have not previously been investigated, despite the fact that women are more prone to cardiovascular disturbances such as neurocardiogenic syncope than men. Therefore, the aim of this study was to explore gender differences in cerebrovascular and cardiovascular responses to EDs. METHODS: We included 45 subjects in a retrospective analysis of pooled data from two previous randomized trials carried out in our laboratory with similar protocols. Beat-to beat blood pressure, impedance cardiography, transcranial Doppler, and end-tidal carbon dioxide (etCO2) measurements were made for at least 20 min baseline and for 80 min following the ingestion of 355 mL of a sugar-sweetened ED. Gender and time differences in cerebrovascular and cardiovascular parameters were investigated. RESULTS: CBFV was significantly reduced in response to ED, with the greatest reduction observed in women compared with men (-12.3 +/- 0.8 vs. -9.7 +/ 0.8%, P < 0.05). Analysis of variance indicated significant time (P < 0.01) and gender * time (P < 0.01) effects. The percentage change in CBFV in response to ED was independent of body weight and etCO2. No significant gender difference in major cardiovascular parameters in response to ED was observed. CONCLUSIONS: ED ingestion reduced CBFV over time, with a greater reduction observed in women compared with men. Our results have potential implications for women ED consumers, as well as high-risk individuals. PMID- 27559317 TI - Maximal Oxygen Consumption Is Reduced in Aquaporin-1 Knockout Mice. AB - We have measured maximal oxygen consumption ([Formula: see text]O2,max) of mice lacking one or two of the established mouse red-cell CO2 channels AQP1, AQP9, and Rhag. We intended to study whether these proteins, by acting as channels for O2, determine O2 exchange in the lung and in the periphery. We found that [Formula: see text]O2,max as determined by the Helox technique is reduced by ~16%, when AQP1 is knocked out, but not when AQP9 or Rhag are lacking. This figure holds for animals respiring normoxic as well as hypoxic gas mixtures. To see whether the reduction of [Formula: see text]O2,max is due to impaired O2 uptake in the lung, we measured carotid arterial O2 saturation (SO2) by pulse oximetry. Neither under normoxic (inspiratory O2 21%) nor under hypoxic conditions (11% O2) is there a difference in SO2 between AQP1null and WT mice, suggesting that AQP1 is not critical for O2 uptake in the lung. The fact that the % reduction of [Formula: see text]O2,max is identical in normoxia and hypoxia indicates moreover that the limitation of [Formula: see text]O2,max is not due to an O2 diffusion problem, neither in the lung nor in the periphery. Instead, it appears likely that AQP1null animals exhibit a reduced [Formula: see text]O2,max due to the reduced wall thickness and muscle mass of the left ventricles of their hearts, as reported previously. We conclude that very likely the properties of the hearts of AQP1 knockout mice cause a reduced maximal cardiac output and thus cause a reduced [Formula: see text]O2,max, which constitutes a new phenotype of these mice. PMID- 27559318 TI - Cycling in the Absence of Task-Related Feedback: Effects on Pacing and Performance. AB - INTRODUCTION: To achieve personal goals in exercise task completion, exercisers have to regulate, distribute, and manage their effort. In endurance sports, it has become very commonplace for athletes to consult task-related feedback on external devices to do so. The aim of the present study was to explore the importance of the presence of this information by examining the influence of the absence of commonly available task-related feedback on effort distribution and performance in experienced endurance athletes. METHODS: A 20-km cycling time trial was performed. Twenty Participants from a homogenous cyclist population were appointed to a group that did not receive any feedback (NoF), or a group that could consult task-related feedback (i.e., speed, heart rate, power output, cadence, elapsed time, and elapsed distance) continuously during their trial (FF). RESULTS: The distribution of power output (PO) differed between groups. Most evident is the spurt at the end of the trial of FF, which was not incorporated by NoF. Nevertheless, no between-group differences were found in performance time (FF: 28.86 +/- 3.68 vs. NoF: 30.95 +/- 2.77 min) and mean PO controlled by body mass (FF: 3.61 +/- 0.60 vs. NoF: 3.43 +/- 0.38 W/kg). Also, no differences in rating of perceived exertion scores were found. CONCLUSION: The current study provides a first indication that prior knowledge of task demands together with reliance on bodily and environmental information can be sufficient for experienced athletes to come to comparable time trial performances. This questions the necessity of the presence of in-race instantaneous task-related feedback via external devices for maximizing performance. Moreover, it seems that different pacing strategies emerge depending on sources of information available to experienced athletes. PMID- 27559319 TI - PREVIEW Behavior Modification Intervention Toolbox (PREMIT): A Study Protocol for a Psychological Element of a Multicenter Project. AB - BACKGROUND: Losing excess body weight and preventing weight regain by changing lifestyle is a challenging but promising task to prevent the incidence of type-2 diabetes. To be successful, it is necessary to use evidence-based and theory driven interventions, which also contribute to the science of behavior modification by providing a deeper understanding of successful intervention components. OBJECTIVE: To develop a physical activity and dietary behavior modification intervention toolbox (PREMIT) that fulfills current requirements of being theory-driven and evidence-based, comprehensively described and feasible to evaluate. PREMIT is part of an intervention trial, which aims to prevent the onset of type-2 diabetes in pre-diabetics in eight clinical centers across the world by guiding them in changing their physical activity and dietary behavior through a group counseling approach. METHODS: The program development took five progressive steps, in line with the Public Health Action Cycle: (1) Summing-up the intervention goal(s), target group and the setting, (2) uncovering the generative psychological mechanisms, (3) identifying behavior change techniques and tools, (4) preparing for evaluation and (5) implementing the intervention and assuring quality. RESULTS: PREMIT is based on a trans-theoretical approach referring to valid behavior modification theories, models and approaches. A major "product" of PREMIT is a matrix, constructed for use by onsite-instructors. The matrix includes objectives, tasks and activities ordered by periods. PREMIT is constructed to help instructors guide participants' behavior change. To ensure high fidelity and adherence of program-implementation across the eight intervention centers standardized operational procedures were defined and "train the-trainer" workshops were held. In summary PREMIT is a theory-driven, evidence based program carefully developed to change physical activity and dietary behaviors in pre-diabetic people. PMID- 27559320 TI - Semantic Processing in Deaf and Hard-of-Hearing Children: Large N400 Mismatch Effects in Brain Responses, Despite Poor Semantic Ability. AB - Difficulties in auditory and phonological processing affect semantic processing in speech comprehension for deaf and hard-of-hearing (DHH) children. However, little is known about brain responses related to semantic processing in this group. We investigated event-related potentials (ERPs) in DHH children with cochlear implants (CIs) and/or hearing aids (HAs), and in normally hearing controls (NH). We used a semantic priming task with spoken word primes followed by picture targets. In both DHH children and controls, cortical response differences between matching and mismatching targets revealed a typical N400 effect associated with semantic processing. Children with CI had the largest mismatch response despite poor semantic abilities overall; Children with CI also had the largest ERP differentiation between mismatch types, with small effects in within-category mismatch trials (target from same category as prime) and large effects in between-category mismatch trials (where target is from a different category than prime), compared to matching trials. Children with NH and HA had similar responses to both mismatch types. While the large and differentiated ERP responses in the CI group were unexpected and should be interpreted with caution, the results could reflect less precision in semantic processing among children with CI, or a stronger reliance on predictive processing. PMID- 27559321 TI - Maternal Weight Predicts Children's Psychosocial Development via Parenting Stress and Emotional Availability. AB - INTRODUCTION: Maternal obesity has been shown to be a risk factor for obesity in children and may also affect children's psychosocial outcomes. It is not yet clear whether there are also psycho-emotional mechanisms explaining the effects of maternal weight on young children's weight and psychosocial development. We aimed to evaluate whether maternal body mass index (BMI), mother-child emotional availability (EA), and maternal parenting stress are associated with children's weight and psychosocial development (i.e., internalizing/externalizing symptoms and social competence) and whether these predictors interact with each other. METHODS: This longitudinal study included three assessment points (~11 months apart). The baseline sample consisted of N = 194 mothers and their children aged 5-47 months (M = 28.18, SD = 8.44, 99 girls). At t 1, we measured maternal weight and height to calculate maternal BMI. We videotaped mother-child interactions, coding them with the EA Scales (fourth edition). We assessed maternal parenting stress with the Parenting Stress Index (PSI) short form. At t 1 to t 3, we measured height and weight of children and calculated BMI-SDS scores. Children's externalizing and internalizing problems (t 1-t 3) and social competence (t 3, N = 118) were assessed using questionnaires: Child Behavior Checklist (CBCL 1.5-5), Strengths and Difficulties Questionnaire (SDQ: prosocial behavior), and a checklist for behavioral problems at preschool age (VBV 3-6: social-emotional competence). RESULTS: By applying structural equation modeling (SEM) and a latent regression analysis, we found maternal BMI to predict higher BMI-SDS and a poorer psychosocial development (higher externalizing symptoms, lower social competence) in children. Higher parenting stress predicted higher levels of externalizing and internalizing symptoms and lower social competence. Better maternal EA was associated with higher social competence. We found parenting stress to serve as a mediator in the association between maternal weight and children's psychosocial outcomes. Moreover, children of mothers with an elevated BMI were at greater risk of lower social competence only when their mothers showed low levels of maternal EA (moderation). CONCLUSION: Interventional studies are needed that investigate the causal pathways between parenting stress, mother-child interaction quality and child outcomes. These aspects might be targets to improve the psychosocial development of the offspring of overweight or obese mothers. PMID- 27559322 TI - Evidence-Based Practice and Psychological Treatments: The Imperatives of Informed Consent. PMID- 27559324 TI - Fluid Intelligence and Cognitive Reflection in a Strategic Environment: Evidence from Dominance-Solvable Games. AB - Dominance solvability is one of the most straightforward solution concepts in game theory. It is based on two principles: dominance (according to which players always use their dominant strategy) and iterated dominance (according to which players always act as if others apply the principle of dominance). However, existing experimental evidence questions the empirical accuracy of dominance solvability. In this study, we study the relationships between the key facets of dominance solvability and two cognitive skills, cognitive reflection, and fluid intelligence. We provide evidence that the behaviors in accordance with dominance and one-step iterated dominance are both predicted by one's fluid intelligence rather than cognitive reflection. Individual cognitive skills, however, only explain a small fraction of the observed failure of dominance solvability. The accuracy of theoretical predictions on strategic decision making thus not only depends on individual cognitive characteristics, but also, perhaps more importantly, on the decision making environment itself. PMID- 27559323 TI - Qualitative Analysis of Emotions: Fear and Thrill. AB - People can speak, and this provides opportunities to analyze human emotions using perceived experiences communicated via language, as well as through measurement and imaging techniques that are also applicable to other higher animal species. Here I compare four qualitative methodological approaches to test if, and how, thrill depends on fear. I use eight high-risk, high-skill, real-life outdoor adventure recreation activities to provide the test circumstances. I present data from: >4000 person-days of participant observation; interviews with 40 expert practitioners; retrospective autoethnography of 50 critical incidents over 4 decades; and experimental autoethnography of 60 events. Results from different methods are congruent, but different approaches yield different insights. The principal findings are as follows. Individuals differ in their fear and thrill responses. The same individual may have different responses on different occasions. Fear boosts performance, but panic causes paralysis. Anxiety or apprehension prior to a risky action or event differs from fear experienced during the event itself. The intensity of pre-event fear generally increases with the immediacy of risk to life, and time to contemplate that risk. Fear must be faced, assessed and overcome in order to act. Thrill can occur either during or after a high-risk event. Thrill can occur without fear, and fear without thrill. Below a lower threshold of perceived risk, thrill can occur without fear. Between a lower and upper threshold, thrill increases with fear. Beyond the upper threshold, thrill vanishes but fear remains. This there is a sawtooth relation between fear and thrill. Perceived danger generates intense focus and awareness. Fear and other emotions can disappear during intense concentration and focus. Under high risk, the usual emotional sequence is fear before the action or event, then focus during the action or event, then thrill, relief, or triumph afterward. The emotionless state persists only during the most intense concentration. For events long enough to differentiate time within the events, fear and thrill can arise and fade in different fine-scale sequences. PMID- 27559325 TI - The Effect of Head Orientation on Perceived Gaze Direction: Revisiting Gibson and Pick (1963) and Cline (1967). AB - Two biases in perceived gaze direction have been observed when eye and head orientation are not aligned. An overshoot effect indicates that perceived gaze direction is shifted away from head orientation (i.e., a repulsive effect), whereas a towing effect indicates that perceived gaze direction falls in between head and eye orientation (i.e., an attraction effect). In the 60s, three influential papers have been published with respect to the effect of head orientation on perceived gaze direction (Gibson and Pick, 1963; Cline, 1967; Anstis et al., 1969). Throughout the years, the results of two of these (Gibson and Pick, 1963; Cline, 1967) have been interpreted differently by a number of authors. In this paper, we critically discuss potential sources of confusion that have led to differential interpretations of both studies. At first sight, the results of Cline (1967), despite having been a major topic of discussion, unambiguously seem to indicate a towing effect whereas Gibson and Pick's (1963) results seem to be the most ambiguous, although they have never been questioned in the literature. To shed further light on this apparent inconsistency, we repeated the critical experiments reported in both studies. Our results indicate an overshoot effect in both studies. PMID- 27559326 TI - Footedness Is Associated with Self-reported Sporting Performance and Motor Abilities in the General Population. AB - Left-handers may have strategic advantages over right-handers in interactive sports and innate superior abilities that are beneficial for sports. Previous studies relied on differing criteria for handedness classification and mostly did not investigate mixed preferences and footedness. Footedness appears to be less influenced by external and societal factors than handedness. Utilizing latent class analysis and structural equation modeling, we investigated in a series of studies (total N > 15300) associations of handedness and footedness with self reported sporting performance and motor abilities in the general population. Using a discovery and a replication sample (ns = 7658 and 5062), Study 1 revealed replicable beneficial effects of mixed-footedness and left-footedness in team sports, martial arts and fencing, dancing, skiing, and swimming. Study 2 (n = 2592) showed that footedness for unskilled bipedal movement tasks, but not for skilled unipedal tasks, was beneficial for sporting performance. Mixed- and left footedness had effects on motor abilities that were consistent with published results on better brain interhemispheric communication, but also akin to testosterone-induced effects regarding flexibility, strength, and endurance. Laterality effects were only small. Possible neural and hormonal bases of observed effects need to be examined in future studies. PMID- 27559327 TI - Mother-Child Communication: The Influence of ADHD Symptomatology and Executive Functioning on Paralinguistic Style. AB - Paralinguistic style, involving features of speech such as pitch and volume, is an important aspect of one's communicative competence. However, little is known about the behavioral traits and cognitive skills that relate to these aspects of speech. This study examined the extent to which ADHD traits and executive functioning (EF) related to the paralinguistic styles of 8- to 12-year-old children and their mothers. Data was collected via parent report (ADHD traits), independent laboratory tasks of EF (working memory, inhibitory control, and cognitive flexibility), and an interactive problem-solving task (completed by mothers and children jointly) which was coded for paralinguistic speech elements (i.e., pitch level/variability; volume level/variability). Dyadic data analyses revealed that elevated ADHD traits in children were associated with a more exaggerated paralinguistic style (i.e., elevated and more variable pitch/volume) for both mothers and children. Mothers' paralinguistic style was additionally predicted by an interaction of mothers' and children's ADHD traits, such that mothers with elevated ADHD traits showed exaggerated paralinguistic styles particularly when their children also had elevated ADHD traits. Highlighting a cognitive mechanism, children with weaker inhibitory control showed more exaggerated paralinguistic styles. PMID- 27559328 TI - Identifying Objective EEG Based Markers of Linear Vection in Depth. AB - This proof-of-concept study investigated whether a time-frequency EEG approach could be used to examine vection (i.e., illusions of self-motion). In the main experiment, we compared the event-related spectral perturbation (ERSP) data of 10 observers during and directly after repeated exposures to two different types of optic flow display (each was 35 degrees wide by 29 degrees high and provided 20 s of motion stimulation). Displays consisted of either a vection display (which simulated constant velocity forward self-motion in depth) or a control display (a spatially scrambled version of the vection display). ERSP data were decomposed using time-frequency Principal Components Analysis (t-f PCA). We found an increase in 10 Hz alpha activity, peaking some 14 s after display motion commenced, which was positively associated with stronger vection ratings. This followed decreases in beta activity, and was also followed by a decrease in delta activity; these decreases in EEG amplitudes were negatively related to the intensity of the vection experience. After display motion ceased, a series of increases in the alpha band also correlated with vection intensity, and appear to reflect vection- and/or motion-aftereffects, as well as later cognitive preparation for reporting the strength of the vection experience. Overall, these findings provide support for the notion that EEG can be used to provide objective markers of changes in both vection status (i.e., "vection/no vection") and vection strength. PMID- 27559330 TI - Narcolepsy Following Yellow Fever Vaccination: A Case Report. AB - Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro immunological disorder. PMID- 27559329 TI - The Role of Sensorimotor Difficulties in Autism Spectrum Conditions. AB - In addition to difficulties in social communication, current diagnostic criteria for autism spectrum conditions (ASC) also incorporate sensorimotor difficulties, repetitive motor movements, and atypical reactivity to sensory input (1). This paper explores whether sensorimotor difficulties are associated with the development and maintenance of symptoms in ASC. First, studies have shown difficulties coordinating sensory input into planning and executing movement effectively in ASC. Second, studies have shown associations between sensory reactivity and motor coordination with core ASC symptoms, suggesting these areas each strongly influence the development of social and communication skills. Third, studies have begun to demonstrate that sensorimotor difficulties in ASC could account for reduced social attention early in development, with a cascading effect on later social, communicative and emotional development. These results suggest that sensorimotor difficulties not only contribute to non-social difficulties such as narrow circumscribed interests, but also to the development of social behaviors such as effectively coordinating eye contact with speech and gesture, interpreting others' behavior, and responding appropriately. Further research is needed to explore the link between sensory and motor difficulties in ASC and their contribution to the development and maintenance of ASC. PMID- 27559331 TI - The Skin Microbiome: Is It Affected by UV-induced Immune Suppression? AB - Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin's microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression. PMID- 27559332 TI - Physiological and Metagenomic Analyses of Microbial Mats Involved in Self Purification of Mine Waters Contaminated with Heavy Metals. AB - Two microbial mats found inside two old (gold and uranium) mines in Zloty Stok and Kowary located in SW Poland seem to form a natural barrier that traps heavy metals leaking from dewatering systems. We performed complex physiological and metagenomic analyses to determine which microorganisms are the main driving agents responsible for self-purification of the mine waters and identify metabolic processes responsible for the observed features. SEM and energy dispersive X-ray microanalysis showed accumulation of heavy metals on the mat surface, whereas, sorption experiments showed that neither microbial mats were completely saturated with heavy metals present in the mine waters, indicating that they have a large potential to absorb significant quantities of metal. The metagenomic analysis revealed that Methylococcaceae and Methylophilaceae families were the most abundant in both communities, moreover, it strongly suggest that backbones of both mats were formed by filamentous bacteria, such as Leptothrix, Thiothrix, and Beggiatoa. The Kowary bacterial community was enriched with the Helicobacteraceae family, whereas the Zloty Stok community consist mainly of Sphingomonadaceae, Rhodobacteraceae, and Caulobacteraceae families. Functional (culture-based) and metagenome (sequence-based) analyses showed that bacteria involved in immobilization of heavy metals, rather than those engaged in mobilization, were the main driving force within the analyzed communities. In turn, a comparison of functional genes revealed that the biofilm formation and heavy metal resistance (HMR) functions are more desirable in microorganisms engaged in water purification than the ability to utilize heavy metals in the respiratory process (oxidation-reduction). These findings provide insight on the activity of bacteria leading, from biofilm formation to self-purification, of mine waters contaminated with heavy metals. PMID- 27559333 TI - Distribution and Niche Separation of Planktonic Microbial Communities in the Water Columns from the Surface to the Hadal Waters of the Japan Trench under the Eutrophic Ocean. AB - The Japan Trench is located under the eutrophic Northwestern Pacific while the Mariana Trench that harbors the unique hadal planktonic biosphere is located under the oligotrophic Pacific. Water samples from the sea surface to just above the seafloor at a total of 11 stations including a trench axis station, were investigated several months after the Tohoku Earthquake in March 2011. High turbidity zones in deep waters were observed at most of the sampling stations. The small subunit (SSU) rRNA gene community structures in the hadal waters (water depths below 6000 m) at the trench axis station were distinct from those in the overlying meso-, bathy and abyssopelagic waters (water depths between 200 and 1000 m, 1000 and 4000 m, and 4000 and 6000 m, respectively), although the SSU rRNA gene sequences suggested that potential heterotrophic bacteria dominated in all of the waters. Potential niche separation of nitrifiers, including ammonia oxidizing archaea (AOA), was revealed by quantitative PCR analyses. It seems likely that Nitrosopumilus-like AOAs respond to a high flux of electron donors and dominate in several zones of water columns including shallow and very deep waters. This study highlights the effects of suspended organic matter, as induced by seafloor deformation, on microbial communities in deep waters and confirm the occurrence of the distinctive hadal biosphere in global trench environments hypothesized in the previous study. PMID- 27559334 TI - The Global Self-Reactivity Profile of the Natural Antibody Repertoire Is Largely Independent of Germline DH Sequence. AB - Natural antibodies (NAbs) are produced in the absence of exogenous antigenic stimulation and circulate in the blood of normal, healthy individuals. These antibodies have been shown to provide one of the first lines of defense against both bacterial and viral pathogens. Conservation of the NAb repertoire reactivity profile is observed both within and across species. One view holds that this conservation of NAb self-reactivities reflects the use of germline antibody sequence, whereas the opposing view holds that the self-reactivities reflect selection driven by key conserved self-antigens. In mice, B-1a B cells are a major source of NAbs. A significant fraction of the B-1a antibody repertoire is devoid of N nucleotides in H chain complementarity determining region 3 (CDR-H3) and, thus, completely germline encoded. To test the role of germline DH sequence on the self-reactivity profile of the NAb repertoire, we examined the composition and self-antigen specificity of NAbs produced by a panel of DH gene-targeted BALB/c mice, each strain of which expresses a polyclonal, altered CDR-H3 repertoire that differs from the wild-type norm. We found that in most cases the same key self-antigens were recognized by the NAbs created by each DH-altered strain. The differences in reactivity appeared to represent the genetic signature of the NAb repertoire of each mouse strain. These findings suggest that although germline CDR-H3 sequence may facilitate the production of certain NAbs, a core set of self-antigens are likely the main force driving the selection of Nab self specificities. PMID- 27559335 TI - ICOS Co-Stimulation: Friend or Foe? AB - Over the last 15 years, the inducible T cell co-stimulator (ICOS) has been implicated in various immune outcomes, including the induction and regulation of Th1, Th2, and Th17 immunity. In addition to its role in directing effector T cell differentiation, ICOS has also been consistently linked with the induction of thymus-dependent (TD) antibody (Ab) responses and the germinal center (GC) reaction. ICOS co-stimulation, therefore, appears to play a complex role in dictating the course of adaptive immunity. In this article, we summarize the initial characterization of ICOS and its relationship with the related co stimulatory molecule CD28. We then address the contribution of ICOS in directing an effector T cell response, and ultimately disease outcome, against various bacterial, viral, and parasitic infections. Next, we assess ICOS in the context of TD Ab responses, connecting ICOS signaling to follicular helper T cell differentiation and its role in the GC reaction. Finally, we address the link between ICOS and human autoimmune disorders and evaluate potential therapies aiming to mitigate disease progression by modulating ICOS signaling. PMID- 27559336 TI - The Plant Cell Wall: A Complex and Dynamic Structure As Revealed by the Responses of Genes under Stress Conditions. AB - The plant cell wall has a diversity of functions. It provides a structural framework to support plant growth and acts as the first line of defense when the plant encounters pathogens. The cell wall must also retain some flexibility, such that when subjected to developmental, biotic, or abiotic stimuli it can be rapidly remodeled in response. Genes encoding enzymes capable of synthesizing or hydrolyzing components of the plant cell wall show differential expression when subjected to different stresses, suggesting they may facilitate stress tolerance through changes in cell wall composition. In this review we summarize recent genetic and transcriptomic data from the literature supporting a role for specific cell wall-related genes in stress responses, in both dicot and monocot systems. These studies highlight that the molecular signatures of cell wall modification are often complex and dynamic, with multiple genes appearing to respond to a given stimulus. Despite this, comparisons between publically available datasets indicate that in many instances cell wall-related genes respond similarly to different pathogens and abiotic stresses, even across the monocot-dicot boundary. We propose that the emerging picture of cell wall remodeling during stress is one that utilizes a common toolkit of cell wall related genes, multiple modifications to cell wall structure, and a defined set of stress-responsive transcription factors that regulate them. PMID- 27559337 TI - Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses. AB - The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica), as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S. italica. mRNA, protein, and metabolite abundances, were measured in mature and immature stem/leaf phytomers, and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP ME and NAD-ME). Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin, and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study, we demonstrated that this systems approach is powerful enough to complement the functional metabolic annotation of bioenergy grasses. PMID- 27559338 TI - Trichome-Related Mutants Provide a New Perspective on Multicellular Trichome Initiation and Development in Cucumber (Cucumis sativus L). AB - Trichomes are specialized epidermal cells located in aerial parts of plants that function in plant defense against biotic and abiotic stresses. The simple unicellular trichomes of Arabidopsis serve as an excellent model to study the molecular mechanism of cell differentiation and pattern formation in plants. Loss of-function mutations in Arabidopsis thaliana have suggested that the core genes GL1 (which encodes a MYB transcription factor) and TTG1 (which encodes a WD40 repeat-containing protein) are important for the initiation and spacing of leaf trichomes, while for normal trichome initiation, the genes GL3, and EGL3 (which encode a bHLH protein) are needed. However, the positive regulatory genes involved in multicellular trichrome development in cucumber remain unclear. This review focuses on the phenotype of mutants (csgl3, tril, tbh, mict, and csgl1) with disturbed trichomes in cucumber and then infers which gene(s) play key roles in trichome initiation and development in those mutants. Evidence indicates that MICT, TBH, and CsGL1 are allelic with alternative splicing. CsGL3 and TRIL are allelic and override the effect of TBH, MICT, and CsGL1 on the regulation of multicellular trichome development; and affect trichome initiation. CsGL3, TRIL, MICT, TBH, and CsGL1 encode HD-Zip proteins with different subfamilies. Genetic and molecular analyses have revealed that CsGL3, TRIL, MICT, TBH, and CsGL1 are responsible for the differentiation of epidermal cells and the development of trichomes. Based on current knowledge, a positive regulator pathway model for trichome development in cucumber was proposed and compared to a model in Arabidopsis. These data suggest that trichome development in cucumber may differ from that in Arabidopsis. PMID- 27559339 TI - Carotenoids in Staple Cereals: Metabolism, Regulation, and Genetic Manipulation. AB - Carotenoids play a critical role in animal and human health. Animals and humans are unable to synthesize carotenoids de novo, and therefore rely upon diet as sources of these compounds. However, major staple cereals often contain only small amounts of carotenoids in their grains. Consequently, there is considerable interest in genetic manipulation of carotenoid content in cereal grain. In this review, we focus on carotenoid metabolism and regulation in non-green plant tissues, as well as genetic manipulation in staple cereals such as rice, maize, and wheat. Significant progress has been made in three aspects: (1) seven carotenogenes play vital roles in carotenoid regulation in non-green plant tissues, including 1-deoxyxylulose-5-phosphate synthase influencing isoprenoid precursor supply, phytoene synthase, beta-cyclase, and epsilon-cyclase controlling biosynthesis, 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase and carotenoid cleavage dioxygenases responsible for degradation, and orange gene conditioning sequestration sink; (2) provitamin A-biofortified crops, such as rice and maize, were developed by either metabolic engineering or marker assisted breeding; (3) quantitative trait loci for carotenoid content on chromosomes 3B, 7A, and 7B were consistently identified, eight carotenogenes including 23 loci were detected, and 10 gene-specific markers for carotenoid accumulation were developed and applied in wheat improvement. A comprehensive and deeper understanding of the regulatory mechanisms of carotenoid metabolism in crops will be beneficial in improving our precision in improving carotenoid contents. Genomic selection and gene editing are emerging as transformative technologies for provitamin A biofortification. PMID- 27559341 TI - Root ABA Accumulation Enhances Rice Seedling Drought Tolerance under Ammonium Supply: Interaction with Aquaporins. AB - In previous studies, we demonstrated that ammonium nutrition enhances the drought tolerance of rice seedlings compared to nitrate nutrition and contributes to a higher root water uptake ability. It remains unclear why rice seedlings maintain a higher water uptake ability when supplied with ammonium under drought stress. Here, we focused on the effects of nitrogen form and drought stress on root abscisic acid (ABA) concentration and aquaporin expression using hydroponics experiments and stimulating drought stress with 10% PEG6000. Drought stress decreased the leaf photosynthetic rate and stomatal conductivity and increased the leaf temperature of plants supplied with either ammonium or nitrate, but especially under nitrate supply. After 4 h of PEG treatment, the root protoplast water permeability and the expression of root PIP and TIP genes decreased in plants supplied with ammonium or nitrate. After 24 h of PEG treatment, the root hydraulic conductivity, the protoplast water permeability, and the expression of some aquaporin genes increased in plants supplied with ammonium compared to those under non-PEG treatment. Root ABA accumulation was induced by 24 h of PEG treatment, especially in plants supplied with ammonium. The addition of exogenous ABA decreased the expression of PIP and TIP genes under non-PEG treatment but increased the expression of some of them under PEG treatment. We concluded that drought stress induced a down-regulation of aquaporin expression, which appeared earlier than did root ABA accumulation. With continued drought stress, aquaporin expression and activity increased due to root ABA accumulation in plants supplied with ammonium. PMID- 27559340 TI - Genome-Wide Comparative Analyses Reveal the Dynamic Evolution of Nucleotide Binding Leucine-Rich Repeat Gene Family among Solanaceae Plants. AB - Plants have evolved an elaborate innate immune system against invading pathogens. Within this system, intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors are known play critical roles in effector-triggered immunity (ETI) plant defense. We performed genome-wide identification and classification of NLR-coding sequences from the genomes of pepper, tomato, and potato using fixed criteria. We then compared genomic duplication and evolution features. We identified intact 267, 443, and 755 NLR-encoding genes in tomato, potato, and pepper genomes, respectively. Phylogenetic analysis and classification of Solanaceae NLRs revealed that the majority of NLR super family members fell into 14 subgroups, including a TIR-NLR (TNL) subgroup and 13 non-TNL subgroups. Specific subgroups have expanded in each genome, with the expansion in pepper showing subgroup-specific physical clusters. Comparative analysis of duplications showed distinct duplication patterns within pepper and among Solanaceae plants suggesting subgroup- or species-specific gene duplication events after speciation, resulting in divergent evolution. Taken together, genome-wide analysis of NLR family members provide insights into their evolutionary history in Solanaceae. These findings also provide important foundational knowledge for understanding NLR evolution and will empower broader characterization of disease resistance genes to be used for crop breeding. PMID- 27559342 TI - Data Mining and Pattern Recognition Models for Identifying Inherited Diseases: Challenges and Implications. AB - Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods in determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI) methods in conjunction with the K nearest neighbors' could be used in accurately categorizing the genetic factors in disease causation. PMID- 27559344 TI - Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains. AB - Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID- 27559345 TI - Cone Beam Computed Tomographic Assessment of Bifid Mandibular Condyle. AB - OBJECTIVES: Differential diagnosis of bifid mandibular condyle (BMC) is important, since it may play a role in temporomandibular joint (TMJ) dysfunctions and joint symptoms. In addition, radiographic appearance of BMC may mimic tumors and/or fractures. The aim of this study was to evaluate the prevalence and orientation of BMC based on cone beam computed tomography (CBCT) scans. MATERIALS AND METHODS: This cross-sectional study was performed on CBCT scans of paranasal sinuses of 425 patients. In a designated NNT station, all CBCT scans were evaluated in the axial, coronal and sagittal planes to find the frequency of BMC. The condylar head horizontal angulations were also determined in the transverse plane. T-test was used to compare the frequency of BMC between the left and right sides and between males and females. RESULTS: Totally, 309 patients with acceptable visibility of condyles on CBCT scans were entered in the study consisting of 170 (55%) females and 139 (45%) males with a mean age of 39.43+/ 9.7 years. The BMC was detected in 14 cases (4.53%). Differences between males and females, sides and horizontal angulations of condyle of normal and BMC cases were not significant. CONCLUSION: The prevalence of BMC in the studied population was 4.53%. No significant difference was observed between males and females, sides or horizontal angulations of the involved and uninvolved condyles. PMID- 27559343 TI - Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility. AB - Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed. PMID- 27559346 TI - Comparison of Marginal Fit and Fracture Strength of a CAD/CAM Zirconia Crown with Two Preparation Designs. AB - OBJECTIVES: The purpose of this in vitro study was to compare the marginal adaptation and fracture resistance of a zirconia-based all-ceramic restoration with two preparation designs. MATERIALS AND METHODS: Twenty-four mandibular premolars were randomly divided into two groups (n=12); the conventional group received a peripheral shoulder preparation and the modified group received a buccal shoulder and proximal/lingual chamfer preparation. The marginal fit of the zirconia crowns (Cercon) was evaluated using a stereomicroscope. After cementation, load was applied to the crowns. The mean fracture load and the mean marginal gap for each group were analyzed using t-test (P=0.05). RESULTS: The mean marginal gap was 71+/-16MUm in the conventional group and 80+/-10MUm in the modified group, with no significant difference (P=0.161). The mean fracture strength was 830+/-153N for the conventional group and 775+/-125N for the modified group, with no significant difference (P=0.396). All but one fracture occurred in the veneering ceramic. CONCLUSION: Less aggressive preparation of proximal and lingual finish lines for the preservation of tooth structure in all ceramic restorations does not adversely affect the marginal adaptation or fracture strength of the final restoration. PMID- 27559347 TI - Effect of Fluoxetine Consumption on Orthodontic Tooth Movement in Rats. AB - OBJECTIVES: Fluoxetine is a selective serotonin re-uptake inhibitor (SSRI) widely used for depression, bipolar disorder, anxiety and obsessive-compulsive disorder. The aim of this study was to assess the effect of fluoxetine on orthodontic tooth movement (OTM) in rats. MATERIALS AND METHODS: Forty-five male Wistar rats were randomly divided into three groups namely the control group (no medication), saline and fluoxetine dissolved in saline. In all groups, nickel titanium closed coil spring was used between the left maxillary central incisor and first molar to exert 60g force at 2mm activation. Radiographs were taken at one and 21 days. After 21 days, the rats were sacrificed. The distance between the first and second molar teeth, optical density of bone, periodontal ligament (PDL) width, lacuna length and depth and number of osteoclasts were measured and compared among the groups. RESULTS: Tooth movement significantly increased in the fluoxetine group (P=0.005). No significant differences were found in osteoclast count (P=0.069). The PDL width in the mesioapical region of root was significantly different among the groups (P=0.015). Statistical analysis did not show significant differences in depth or length of lacunae in any examined part of the root (P>0.05). Bone densitometry results showed that in fluoxetine group, density of bone in all four areas (alveolar bone, hard palate, skull and mandibular bone) significantly decreased from day one to day 21 (P< 0.05). CONCLUSION: This study indicated that fluoxetine decreased bone density, which resulted in subsequently greater tooth movement in rats; however, further studies are needed on humans. PMID- 27559348 TI - Effect of an Extra Hydrophobic Resin Layer on Repair Shear Bond Strength of a Silorane-Based Composite Resin. AB - OBJECTIVES: Composite repair is a minimally invasive and conservative approach. This study aimed to evaluate the effect of an additional hydrophobic resin layer on the repair shear bond strength of a silorane-based composite repaired with silorane or methacrylate-based composite. MATERIALS AND METHODS: Sixty bar-shaped composite blocks were fabricated and stored in saline for 72 hours. The surface of the samples were roughened by diamond burs and etched with phosphoric acid; then, they were randomly divided into three groups according to the repairing process: Group 1: Silorane composite-silorane bonding agent-silorane composite; group 2: Silorane composite-silorane bonding agent-hydrophobic resin-silorane composite, and group 3: Silorane composite-silorane bonding agent-hydrophobic resin methacrylate-based composite. Repairing composite blocks measured 2.5*2.5*5mm. After repairing, the samples were stored in saline for 24 hours and thermocycled for 1500 cycles. The repair bond strength was measured at a strain rate of 1mm/min. Twenty additional cylindrical composite blocks (diameter: 2.5mm, height: 6mm) were also fabricated for measuring the cohesive strength of silorane based composite. The data were analyzed using One-way ANOVA and the post hoc Tukey's test (alpha=0.05). RESULTS: Cohesive bond strength of silorane composite was significantly higher than the repair bond strengths in other groups (P<0.001). The repair bond strength of group 3 was significantly higher than that of group 1 (P=0.001). CONCLUSION: Application of an additional hydrophobic resin layer for repair of silorane-based composite with a methacrylate-based composite enhanced the repair shear bond strength. PMID- 27559349 TI - Root Surface Roughness After Scaling and Root Planing with Er:YAG Laser Compared to Hand and Ultrasonic Instruments by Profilometry. AB - OBJECTIVES: Scaling and root planing (SRP) is one of the most commonly used procedures during periodontal treatment. The aim of this study was to evaluate the root surface roughness after SRP with erbium: yttrium aluminum garnet (Er:YAG) laser compared to ultrasonic and hand instruments. MATERIALS AND METHODS: In this experimental study, 56 extracted sound single-rooted teeth with moderate level of calculus were selected and randomly divided into four groups: SRP was performed with Er:YAG laser (100 mJ pulse, 1W, 10Hz, VSP and contact mode, with 50% water and air) in group one, hand instrument in group two and ultrasonic tool in group three. Group four was considered as the control group. After SRP, all samples were cut by Servocut cutting machine into pieces with 3*3*2mm dimensions. The samples were mounted in acrylic resin. The surface roughness of the samples was evaluated with profilometry, and the data were analyzed using one-way ANOVA and Tukey's test in SPSS software. RESULTS: Surface roughness was higher in laser and lower in ultrasonic group compared to other groups. There was a significant difference in surface roughness between laser and ultrasonic groups (P=0.043), but there was no significant difference in surface roughness among other groups (P>0.05). CONCLUSION: The results of this study showed that surface roughness after SRP with Er:YAG laser was not higher than that after manual SRP, but the former value was higher than that after SRP with ultrasonic instrument. PMID- 27559350 TI - Frequency of Dental Implants Placed in the Esthetic Zone in Dental Clinic of Tehran University: A Descriptive Study. AB - OBJECTIVES: Anterior maxilla, known as the esthetic zone, plays an important role in facial and smile esthetics. This study assessed the frequency of implant treatments in the esthetic zone of patients presenting to Dental Implant Department of Tehran University during 2002-2012. MATERIALS AND METHODS: This descriptive study was conducted on dental records of patients receiving implant treatment during 2002-2012. Patient records were retrieved from the archives and patient demographics, implant characteristics, failure rate, prevalence of complications and implant systems were collected. The data were reported as frequency and percentage. RESULTS: Of a total of 2,381 implants placed in the mentioned time period, 492 (20.8%) had been placed in the anterior maxilla and 531 (22.3%) had been placed in the anterior mandible from canine to canine. Timing of implant placement was immediate in 12.0%, early in 0.5% and late in 87.4%. Survival rate was 99.1%. Rate of failure was 0.8%. Failure rate was 0.4% in the maxillary and 1.1% in the mandibular canine to canine region. Complications were reported in 10.1% of patients. Rate of complications was 18.3% in the maxillary canine to canine, 8.9% in the mandibular canine to canine, 18.1% in the maxillary first premolar to first premolar and 9.5% in the mandibular first premolar to first premolar. The frequency of bone grafts placed in these areas was 17.6%, 33.9%, 13.6%, 32.1% and 14.3%, respectively. CONCLUSION: Of implants placed in our center, around 20% were in the anterior maxilla, and delayed implant placement was the most commonly adopted technique. PMID- 27559351 TI - Efficacy of Glass Ionomer Cements for Prevention of White Spot Lesions During Orthodontic Banding: A Randomized Clinical Trial. AB - OBJECTIVES: This study aimed to compare the incidence of white spot lesions (WSLs) around orthodontic bands following the application of two glass ionomer (GI) cements namely GC Gold Label and GC Fuji Plus for six to 12 months. MATERIALS AND METHODS: A total of 186 permanent first molars of orthodontic patients requiring banding of at least two permanent first molars were chosen. The teeth were examined for caries and presence of WSLs by visual inspection and by DIAGNOdent (scores 0-29). Orthodontic bands were randomly cemented to the right or left molars using GC Gold Label or GC Fuji Plus GI cements. Samples were randomly divided into three groups and bands were removed after six, nine and 12 months in groups 1, 2 and 3, respectively. The teeth were then examined for caries and presence of WSLs by visual inspection. DIAGNOdent was used on the buccal and lingual surfaces to determine the presence of WSLs. The data were statistically analyzed using one-way ANOVA, multivariate repeated measures ANOVA, the Kruskal Wallis and the Mann-Whitney tests. RESULTS: Totally 174 teeth were evaluated. DIAGNOdent scores were not significantly different before cementation and after removal of bands in buccal and lingual surfaces of the teeth in the two cement groups. Lesions simulating WSLs were seen in 21 out of 174 teeth but DIAGNOdent scores were not indicative of caries. CONCLUSION: Remarkable WSLs were not detected visually or by DIAGNOdent at six, nine or 12 months following the cementation of bands with two GI cements. PMID- 27559352 TI - Temperature Rise Induced by Light Curing Unit Can Shorten Enamel Acid-Etching Time. AB - OBJECTIVES: The aim of this in-vitro study was to assess the thermal effect of light emitting diode (LED) light curing unit on the enamel etching time. MATERIALS AND METHODS: Three treatment groups with 15 enamel specimens each were used in this study: G1: Fifteen seconds of etching, G2: Five seconds of etching, G3: Five seconds of etching plus LED light irradiation (simultaneously). The micro shear bond strength (MUSBS) of composite resin to enamel was measured. RESULTS: The mean MUSBS values +/- standard deviation were 51.28+/-2.35, 40.47+/ 2.75 and 50.00+/-2.59 MPa in groups 1, 2 and 3, respectively. There was a significant difference between groups 1 and 2 (P=0.013) and between groups 2 and 3 (P=0.032) in this respect, while there was no difference between groups 1 and 3 (P=0.932). CONCLUSION: Simultaneous application of phosphoric acid gel over enamel surface and light irradiation using a LED light curing unit decreased enamel etching time to five seconds without compromising the MUSBS. PMID- 27559353 TI - Comparison of Marginal Circumference of Two Different Pre-Crimped Stainless Steel Crowns for Primary Molars After Re-Crimping. AB - OBJECTIVES: It is not clear what type of pre-crimped crown is more successful in achieving greater marginal adaptation following re-crimping. This study aimed to assess the changes in the circumference of 3M ESPE and MIB pre-crimped stainless steel crowns (SSCs) for the primary maxillary and mandibular first and second molars following re-crimping. MATERIALS AND METHODS: This was an in-vitro, experimental study. Initial photographs were obtained from the margins of 3M and MIB SSCs for the upper and lower primary molars using a digital camera. Crown margins were crimped by applying 0.2N force using 114 and 137 pliers. Post crimping photographs were also obtained and the changes in crown circumference after crimping were calculated using AutoCad software. The percentage of reduction in the circumference of crowns for each tooth was statistically analyzed based on the type of crown using student t-test. The effect of crown design and the associated teeth on the decreased circumference percentage was statistically analyzed by two-sided ANOVA. RESULTS: The percentage of reduction in lower E SSC circumference was 3.71+/-0.39% in MIB and 6.29+/-0.62% in 3M crowns. These values were 3.55+/-0.55% and 7.15+/-1.13% for the lower Ds, and 3.95+/-0.43 and 6.24+/-0.85% for the upper Ds, respectively. For the upper Es, these values were found to be 3.12+/-0.65% and 5.14+/-0.94%, respectively. For each tooth, a significant difference was found between MIB and 3M SSCs in terms of the percentage of reduction in crown circumference following crimping. The magnitude of this reduction was smaller in MIB compared to 3M SSCs (P<0.001). CONCLUSION: Considering the significant reduction in the marginal circumference of precrimped SSCs following re-crimping, it appears that this manipulation must be necessarily performed for MIB and 3M pre-crimped SSCs. By using 3M SSCs, higher marginal adaptation can be achieved following crimping. PMID- 27559354 TI - Fabrication of an Implant-Supported Orbital Prosthesis with Bar-Magnetic Attachment: A Clinical Report. AB - Implant-supported craniofacial prostheses are made to restore defective areas in the face and cranium. This clinical report describes a technique for fabrication of an orbital prosthesis with three adjacent implants in the left lateral orbital rim of a 60-year-old woman. Selection of appropriate attachment system (individual magnetic abutments versus bar-clip attachment) for implant-supported orbital prostheses depends upon the position of implants. Bar-magnetic attachment has been selected as the retention mechanism in the present case. PMID- 27559355 TI - The inflammatory protein Pentraxin 3 in cardiovascular disease. AB - The acute phase protein Pentraxin 3 (PTX3) plays a non-redundant role as a soluble pattern recognition receptor for selected pathogens and it represents a rapid biomarker for primary local activation of innate immunity and inflammation. Recent evidence indicates that PTX3 exerts an important role in modulating the cardiovascular system in humans and experimental models. In particular, there are conflicting points concerning the effects of PTX3 in cardiovascular diseases (CVD) since several observations indicate a cardiovascular protective effect of PTX3 while others speculate that the increased plasma levels of PTX3 in subjects with CVD correlate with disease severity and with poor prognosis in elderly patients. In the present review, we discuss the multifaceted effects of PTX3 on the cardiovascular system focusing on its involvement in atherosclerosis, endothelial function, hypertension, myocardial infarction and angiogenesis. This may help to explain how the specific modulation of PTX3 such as the use of different dosing, time, and target organs could help to contain different vascular diseases. These opposite actions of PTX3 will be emphasized concerning the modulation of cardiovascular system where potential therapeutic implications of PTX3 in humans are discussed. PMID- 27559356 TI - Artificial selection reveals the energetic expense of producing larger eggs. AB - BACKGROUND: The amount of resources provided by the mother before birth has important and long-lasting effects on offspring fitness. Despite this, there is a large amount of variation in maternal investment seen in natural populations. Life-history theory predicts that this variation is maintained through a trade off between the benefits of high maternal investment for the offspring and the costs of high investment for the mother. However, the proximate mechanisms underlying these costs of reproduction are not well understood. Here we used artificial selection for high and low maternal egg investment in a precocial bird, the Japanese quail (Coturnix japonica) to quantify costs of maternal reproductive investment. RESULTS: We show that females from the high maternal investment lines had significantly larger reproductive organs, which explained their overall larger body mass, and resulted in a higher resting metabolic rate (RMR). Contrary to our expectations, this increase in metabolic activity did not lead to a higher level of oxidative damage. CONCLUSIONS: This study is the first to provide experimental evidence for metabolic costs of increased per offspring investment. PMID- 27559357 TI - Prolonged transfer of feces from the lean mice modulates gut microbiota in obese mice. AB - BACKGROUND: Transplanting a fecal sample from lean, healthy donors to obese recipients has been shown to improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering a long-term, high-fat diet (HFD) supplemented with feces from lean mice through the fecal-oral route. METHODS: C57BL6/W mice were allowed to adapt to a non-specific pathogen free (SFP) environment for 2 weeks before being divided into three groups of 16 animals. Animals were fed for 28 weeks with a normal diet (ND), HFD or HFD supplemented with feces from ND-fed mice (HFDS). The composition of colonizing bacteria was evaluated in droppings collected under SPF conditions at the beginning of the study and at 12 and 28 weeks using an 16S Metagenomics Kit on Ion PGM sequencer. RESULTS: HFD and HFDS-fed mice attained (p < 0.05) greater body weights by weeks 6 and 5, respectively. HFDS-fed mice gained more weight than HFD-fed mice by week 25. Both species diversity and richness indices increased with time in HFDS mice only. CONCLUSIONS: Prolonged HFD-fed mice supplementation with feces from lean mice altered bacteria species diversity and richness, accelerated the onset of obesity, and caused increased weight gain in the later weeks of the HFD regimen. PMID- 27559358 TI - Effects of dietary fat subtypes on glucose homeostasis during pregnancy in rats. AB - BACKGROUND: Dietary n-3 and n-6 polyunsaturated fatty acids (PUFAs) have an impact on insulin secretion and sensitivity but whether and how these may be related to maternal glucose homeostasis during pregnancy is unclear. METHODS: Female Wistar rats (240-250 g) were assigned to laboratory CHOW or high fat diets rich in either n-6 (safflower oil; n-6 group) or n-6 + n-3 (safflower oil + fish oil; n-3 group) PUFAs. After 10 days half of the animals in each diet group were inseminated and confirmed pregnant. An overnight fasted intravenous glucose tolerance test (500 mg glucose/kg body weight) was performed on chronically cannulated non-pregnant and 20-day pregnant rats. Indices of insulin secretion (beta) and insulin sensitivity (S) were calculated from the plasma glucose and insulin responses. The fatty acid composition of phospholipids was determined in samples of liver and two skeletal muscles (soleus and red quadriceps). RESULTS: Pregnancy in the CHOW group significantly increased beta (P < 0.001) and decreased S (P < 0.01). In contrast, both n-6 and n-3 diets abolished both the pregnancy-induced decrease in S and pregnancy-induced increase in beta with the n 3 diet having a more potent effect on both S and beta. S was positively correlated with the sum of n-3 fatty acids, with docosahexaenoic acid (22:6 n-3) the major contributor, in liver (r = 0.485; P < 0.001), red quadriceps (r = 0.421; P = 0.004) and soleus (r = 0.476; P < 0.001). In contrast S was inversely related to arachidonic acid (20:4n-6) levels in liver and red quadriceps across all groups and these relationships were particularly powerful in pregnancy (liver: r = -0.785; red quadriceps: r = -0.754, both P < 0.0001). CONCLUSIONS: The results demonstrate potent effects of dietary fat amount and profile on glucoregulation during pregnancy and emphasize the importance of the balance between dietary n-3 and n-6 PUFAs. PMID- 27559359 TI - HPV-16 infection modifies overall survival of Puerto Rican HNSCC patients. AB - BACKGROUND: HPV-16 modifies the overall survival (OS) of patients with oropharyngeal cancer (OPSCC). HPV-16 has been established as risk factor for OPSCC, but HPV-16 infection may also reside in the larynx and oral cavity. We evaluated HPV-16 status on OS of Head and Neck Squamous Cell Carcinoma (HNSCC) patients. METHODS: HPV-16 infection was confirmed by amplification of E6 and E7 viral oncogenes through PCR assay and E6 IHC in 185 HNSCC samples. Associations between HPV-16 status and clinicopathological parameters were performed using Fisher's exact test and x(2). Survival analysis was completed using Kaplan-Meier estimator and multivariate Cox regression analysis. RESULTS: OS of HPV-16 positive patients was longer compared to HPV-16 negative patients (P = 0.002). HPV-16 positive tumors of the larynx (LSCC) and pharynx (PSCC) showed improved OS compared to HPV-16 negative tumors. Also, HPV-16 positive patients exposed to radiotherapy presented a better survival. CONCLUSIONS: HPV-16 status has a positive prognostic value in HNSCC. Addition of HPV-16 status to the TNM staging can provide better assessment in prognosis and guide treatment for HNSCC patients. PMID- 27559360 TI - Facile isothermal solid acid catalyzed ionic liquid pretreatments to enhance the combined sugars production from Arundo donax Linn. AB - BACKGROUND: Solid acid catalyzed inexpensive ionic liquid (IL) pretreatment is promising because of its effectiveness at decreasing biomass recalcitrance to subsequent enzymatic hydrolysis or in situ hydrolysis of carbohydrate oligomers. However, the conventional strategy was limited by the complex non-isothermal process and considering only one aspect of sugar recovery. In this study, facile isothermal pretreatments using Amberlyst 35DRY catalyzed 1-n-butyl-3 methylimidazolium chloride ([C4mim]Cl) at mild conditions were developed on bioenergy crop Arundo donax Linn. to enhance the combined sugars released. The physicochemical differences, enzymatic digestibility, and sugars released in situ were evaluated and compared to define the best set of conditions. RESULTS: The optimized isothermal pretreatment (110 degrees C, IL for 3 h, Amberlyst for 1 h) resulted in significant enhancement in combined sugars released (58.4 g/100 g raw materials), recovering 85.0 % of the total reducing glycan in the raw biomass. This remarkable improvement could be correlated to cellulose crystallinity reduction, crystalline conversion, and partial removal of the main chemical components caused by the pretreatment. Particularly, solubilization of hemicelluloses and partial depolymerization of cellulose contributed to the synergetic improvement of sugars production in enzymatic hydrolysis and in situ. Irrespective of the generous differences in mass recovery, the highest cellulose digestibility of 90.2 % and sugar released of 43.0 % (based on initial materials) in the pretreatment liquor were obtained. Interestingly, lignin (0.8-6.1 %) and sugars derived lactic acid (4.70-5.94 %) were produced without any notable deleterious effects. CONCLUSIONS: Isothermal [C4mim]Cl-Amberlyst pretreatment was a highly effective, simple, and convenient process that produced high yields of fermentable sugars from recalcitrant biomass by in situ hydrolysis of soluble biomass and enhancement of cellulose digestibility of the regenerated biomass. Relatively high amount of new revenues beyond sugars of this pretreatment could promote the commercial viability. PMID- 27559361 TI - Maternal uniparental disomy 14 and mosaic trisomy 14 in a Chinese boy with moderate to severe intellectual disability. AB - BACKGROUND: Both maternal uniparental disomy 14 (UPD(14)mat) and mosaic trisomy 14 are rare events in live individuals. A combination of the two events in one individual is rarely encountered. Only six live-born cases have so far been reported. CASE PRESENTATION: Here we reported a case of concomitant UPD(14)mat and mosaic trisomy 14 in a 10-year-old Chinese patient. Most clinical features of our patient were consistent with those previous reported for UPD(14)mat cases, which include prenatal and postnatal growth retardation, neonatal hypotonia, feeding difficulty, intellectual disability, truncal obesity, small hands and feet, short stature, and mild facial dysmorphism, but our patient showed more severe intellectual disability and no sign of precocious puberty. SNP array analysis revealed a mixture of chromosome 14 maternal isodisomy with heterodisomy and a low level trisomy mosaicism of whole chromsome 14 in blood and hyperpigmented skin samples, whereas only UPD(14)mat was detected in normal skin sample. Cytogenetic analysis identified one trisomy 14 cell in 100 metaphase of peripheral blood lymphocytes (47,XX, +14[1]/46,XX[99]). CONCLUSIONS: To our knowledge, this is the first case of a patient with UPD(14)mat and mosaic trisomy 14 reported in a Chinese patient. The definitive genetic diagnosis is beneficial for genetic counseling and clinical management of our patient, and for improving our understanding of the genotype-phenotype correlations of concomitant UPD(14)mat and mosaic trisomy 14. PMID- 27559362 TI - Study design. AB - A brief survey is provided of common designs for medical studies and important issues in their implementation. The designs discussed include those for laboratory studies, clinical trials, cohort studies, case-control and related studies, and diagnostic studies. PMID- 27559363 TI - Dietary factors associated with metabolic syndrome and its components in overweight and obese Brazilian schoolchildren: a cross-sectional study. AB - BACKGROUND: The metabolic syndrome (MS) has been assessed since childhood mainly because of the nutritional and epidemiological transition that has occurred worldwide. Our objectives were to explore the MS and its components according to anthropometric and demographic factors and to assess the relationship among MS components and dietary characteristics in overweight and obese schoolchildren. METHODS: This was a cross-sectional study which included 147 schoolchildren (aged 6-10 years) from three elementary schools, with body mass index (BMI) higher than the 85th percentile. Sexual maturation stages, anthropometric measures (weight, height, skinfold thickness and waist circumference), biochemical data (glucose, HDL-C and triacylglycerol), blood pressure and dietary intake were assessed. The metabolic syndrome was diagnosed if three or more of the following components were presented: waist circumference >=90th age and sex-specific cut-off, blood pressure >=90th age, sex and height-specific cut-off, glucose >=100 mg/dL, HDL-C >= 40 mg/dL and triacylglycerols >= 110 mg/dL. The dietary intake was assessed by three non-consecutive 24-h recalls. The T test, Kruskal-Wallis and multiple linear regression analysis were applied to assess MS components and dietary intake. RESULTS: The MS percentage was 10.2 % and it was higher in obese children and ones with high body fat percentage. The waist circumference was the main altered component of MS and 62 % of overweight schoolchildren showed at least one altered component of MS. The components of metabolic syndrome associated with dietary intake were triacylglycerol (positive association with saturated and monounsaturated fat, whole-milk products and processed foods and negative associated with legumes and polyunsaturated fat), glycemia (positive association with processed foods and negative with cereals), HDL-C (positive association with vegetables and greens) and waist circumference was negative associated with protein. CONCLUSIONS: The frequency of MS was higher in obese than overweight schoolchildren and the frequency of at least one MS component was high in more than half of our subjects. The waist circumference was the most frequent among all other components. The triacylglycerol and glycemia were the most frequent MS components associated with dietary intake. Unprocessed food was considered a protective dietary factor for MS metabolic components and processed food with high percentage of sugar and saturated fat was a risk factor for MS metabolic components. PMID- 27559364 TI - The impact of the metabolic phenotype on thyroid function in obesity. AB - BACKGROUND: Obesity is known to promote mild hyperthyrotropinaemia by unknown metabolic mechanisms. This investigation aimed to explore the association between thyroid function and metabolic phenotype in euthyroid obese individuals. Retrospective, cross-sectional study. Tertiary care center. METHODS: 952 euthyroid obese individuals referred to our Institution for obesity. Serum levels of TSH, FT4, glucose, insulin and HbA1c levels, lipid profile, liver function and proinflammatory indices were measured. Resting energy expenditure was assessed by indirect calorimetry and body composition by bioimpedance analysis. RESULTS: On admission, 306 patients had previously diagnosed diabetes mellitus on treatment with metformin, while 113 patients were diagnosed with incident diabetes mellitus. Serum TSH levels were similar between metformin-treated diabetic subjects and metformin-untreated subjects, while FT4 was slightly but significantly higher in the former. Analysis stratified by TSH categories found no effect of metformin-treated diabetes mellitus on TSH levels. Interestingly, obese patients with incident diabetes showed lower TSH levels than normoglycaemic ones. In correlation studies on the whole dataset, an association related TSH to BMI and total cholesterol levels, which was lost upon adjustment for individual confounders. FT4 levels were found to be inversely related to BMI, insulin resistance and triglycerides, while being directly associated with HDL cholesterol levels. These correlations remained unaltered after controlling for individual confounders. In multivariate linear regression analysis, TSH was associated with FT4, total cholesterol and BMI values. Significant predictors of FT4 were constituted by previously diagnosed diabetes mellitus, BMI, TSH and age. CONCLUSIONS: In euthyroid obese subjects, FT4 seems more closely related than TSH levels to parameters of cardiometabolic risk. TSH levels did not differ between metformin-treated and untreated subjects, while they were lower in patients with incident diabetes mellitus compared to normoglycaemic ones. PMID- 27559365 TI - Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines. AB - The synthesis of omega-di-(trideuteromethyl)-trisnorsqualenic acid has been achieved from natural squalene. The synthesis features the use of a Shapiro reaction of acetone-d 6 trisylhydrazone as a key step to implement the terminal isopropylidene-d 6 moiety. The obtained squalenic acid-d 6 has been coupled to gemcitabine to provide the deuterated analogue of squalenoyl gemcitabine, a powerful anticancer agent endowed with self-assembling properties. The Raman spectra of both deuterated and non-deuterated squalenoyl gemcitabine nanoparticles displayed significant Raman scattering signals. They revealed no differences except from the deuterium peak patterns in the silent spectral region of cells. This paves the way for label-free intracellular trafficking studies of squalenoyl nanomedicines. PMID- 27559366 TI - Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization. AB - A full account of our efforts toward an asymmetric redox bicycloisomerization reaction is presented in this article. Cyclopentadienylruthenium (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the asymmetric redox bicycloisomerization of 1,6- and 1,7-enynes. This complex was used to synthesize a broad array of [3.1.0] and [4.1.0] bicycles. Sulfonamide- and phosphoramidate-containing products could be deprotected under reducing conditions. Catalysis performed with enantiomerically enriched propargyl alcohols revealed a matched/mismatched effect that was strongly dependent on the nature of the solvent. PMID- 27559367 TI - Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp(2) C-H and sp(3) C-H bonds. AB - The synthesis of a variety of 2-oxindoles bearing an all-carbon quaternary center at the pseudo benzylic position has been achieved via a 'transition-metal-free' intramolecular dehydrogenative coupling (IDC). The construction of 2-oxindole moieties was carried out through formation of carbon-carbon bonds using KOt-Bu catalyzed one pot C-alkylation of beta-N-arylamido esters with alkyl halides followed by a dehydrogenative coupling. Experimental evidences indicated toward a radical-mediated path for this reaction. PMID- 27559368 TI - Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of beta ketoenamides - scope and limitations. AB - The scope of a flexible route to unsymmetrically functionalized bipyridines is described. Starting from 1,3-diketones 1a-e, the corresponding beta-ketoenamines 2a-e were converted into different beta-ketoenamides 3a-g by N-acylation with 2 pyridinecarboxylic acid derivatives. These beta-ketoenamides were treated with a mixture of TMSOTf and Hunig's base to promote the cyclocondensation to 4 hydroxypyridine derivatives. Their immediate O-nonaflation employing nonafluorobutanesulfonyl fluoride provided the expected 4-nonafloxy-substituted bipyridine derivatives 5a-g in moderate to good overall yields. The bipyridyl nonaflates are excellent precursors for palladium-catalyzed reactions as demonstrated by representative Suzuki and Sonogashira couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. PMID- 27559369 TI - Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene. AB - Do not rely on the widely accepted rule that vicinal, sp(3)-positioned protons in cyclopentene moieties should always have more positive (3) J NMR coupling constants for the cis than for the trans arrangement: Unrecognized exceptions might misguide one to wrong stereochemical assignments and thence to erroneous mechanistic conclusions. We show here that two structurally innocent-looking 2,3 dibromo-1,1-dimethylindanes violate the rule by means of their values of (3) J(cis) = 6.1 Hz and (3) J(trans) = 8.4 Hz. The stereoselective formation of the trans diastereomer from 1,1-dimethylindene was improved with the tribromide anion (Br3 (-)) as the brominating agent in place of elemental bromine; the ensuing, regiospecific HBr elimination afforded 3-bromo-1,1-dimethylindene. The addition of elemental bromine to the latter compound, followed by thermal HBr elimination, furnished 2,3-dibromo-1,1-dimethylindene, whose Br/Li interchange reaction, precipitation, and subsequent protolysis yielded only 2-bromo-1,1-dimethylindene. PMID- 27559370 TI - NeoPHOX - a structurally tunable ligand system for asymmetric catalysis. AB - A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central intermediate is a NeoPHOX derivative bearing a methoxycarbonyl group at the stereogenic center next to the oxazoline N atom. The addition of methylmagnesium chloride leads to a tertiary alcohol, which can be acylated or silylated to produce NeoPHOX ligands with different sterical demand. The new NeoPHOX ligands were tested in the iridium-catalyzed asymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions high enantioselectivities were achieved, that were comparable to the enantioselectivities obtained with the up to now best NeoPHOX ligand derived from expensive tert-leucine. PMID- 27559371 TI - Biradical vs singlet oxygen photogeneration in suprofen-cholesterol systems. AB - Cholesterol (Ch) is an important lipidic building block and a target for oxidative degradation, which can be induced via free radicals or singlet oxygen ((1)O2). Suprofen (SP) is a nonsteroidal anti-inflammatory drug that contains the 2-benzoylthiophene (BZT) chromophore and has a pi,pi* lowest triplet excited state. In the present work, dyads (S)- and (R)-SP-alpha-Ch (1 and 2), as well as (S)-SP-beta-Ch (3) have been prepared from beta- or alpha-Ch and SP to investigate the possible competition between photogeneration of biradicals and (1)O2, the key mechanistic steps in Ch photooxidation. Steady-state irradiation of 1 and 2 was performed in dichloromethane, under nitrogen, through Pyrex, using a 400 W medium pressure mercury lamp. The spectral analysis of the separated fractions revealed formation of two photoproducts 4 and 5, respectively. By contrast, under the same conditions, 3 did not give rise to any isolable Ch derived product. These results point to an intramolecular hydrogen abstraction in 1 and 2 from the C7 position of Ch and subsequent C-C coupling of the generated biradicals. Interestingly, 2 was significantly more photoreactive than 1 indicating a clear stereodifferentiation in the photochemical behavior. Transient absorption spectra obtained for 1-3 were very similar and matched that described for the SP triplet excited state (typical bands with maxima at ca. 350 nm and 600 nm). Direct kinetic analysis of the decay traces at 620 nm led to determination of triplet lifetimes that were ca. 4.1 MUs for 1 and 2 and 5.8 MUs for 3. From these data, the intramolecular quenching rate constants in 1 and 2 were determined as 0.78 * 10(5) s(-1). The capability of dyads 1-3 to photosensitize the production of singlet oxygen was assessed by time-resolved near infrared emission studies in dichloromethane using perinaphthenone as standard. The quantum yields (PhiDelta) were 0.52 for 1 and 2 and 0.56 for 3. In conclusion, SP alpha-Ch dyads are unique in the sense that they can be used to photogenerate both biradicals and singlet oxygen, thus being able to initiate Ch oxidation from their triplet excited states following either of the two competing mechanistic pathways. PMID- 27559372 TI - Conjugate addition-enantioselective protonation reactions. AB - The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. PMID- 27559373 TI - Synthesis, fluorescence properties and the promising cytotoxicity of pyrene derived aminophosphonates. AB - A large series of variously substituted amino(pyren-1-yl)methylphosphonic acid derivatives was synthesized using a modified aza-Pudovik reaction in 20-97% yields. The fluorescence properties of the obtained compounds were investigated revealing that N-alkylamino(pyren-1-yl)methylphosphonic derivatives are stronger emissive compounds than the corresponding N-aryl derivatives. N-Benzylamino(pyren 1-yl)methylphosphonic acid displayed strong fluorescence (PhiF = 0.68) in phosphate-buffered saline (PBS). The influence of a series of derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 MUM), simultaneously showing weak toxicity towards normal lymphocytes (IC50 = 230.8 uM). PMID- 27559374 TI - Stereoselective synthesis of tricyclic compounds by intramolecular palladium catalyzed addition of aryl iodides to carbonyl groups. AB - Starting from gamma-ketoesters with an o-iodobenzyl group we studied a palladium catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID- 27559375 TI - Palladium-catalyzed picolinamide-directed iodination of remote ortho-C-H bonds of arenes: Synthesis of tetrahydroquinolines. AB - A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of epsilon-C(sp(2))-H bonds of gamma-arylpropylamine substrates is reported. This reaction proceeds selectively with a variety of gamma-arylpropylamines bearing strongly electron-donating or withdrawing substituents, complementing our previously reported PA-directed electrophilic aromatic substitution approach to this transformation. As demonstrated herein, a three step sequence of Pd catalyzed gamma-C(sp(3))-H arylation, Pd-catalyzed epsilon-C(sp(2))-H iodination, and Cu-catalyzed C-N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns. PMID- 27559377 TI - Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates. AB - Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry. As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic compounds bearing a phosphonate group on the ring is given. PMID- 27559378 TI - Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene. AB - A new strategy for the synthesis of 2-substituted tetraphenylenes through a transition-metal-catalyzed derivatization has been developed. Three types of functionalities, including OAc, X (Cl, Br, I) and carbonyl, were introduced onto tetraphenylene, which allows the easy access to a variety of monosubstituted tetraphenylenes. These reactions could accelerate research on the properties and application of tetraphenylene derivatives. PMID- 27559376 TI - Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post translationally modified peptides. AB - Ribosomally synthesised and post-translationally modified peptides (RiPPs) are a large class of natural products that are remarkably chemically diverse given an intrinsic requirement to be assembled from proteinogenic amino acids. The vast chemical space occupied by RiPPs means that they possess a wide variety of biological activities, and the class includes antibiotics, co-factors, signalling molecules, anticancer and anti-HIV compounds, and toxins. A considerable amount of RiPP chemical diversity is generated from cyclisation reactions, and the current mechanistic understanding of these reactions will be discussed here. These cyclisations involve a diverse array of chemical reactions, including 1,4 nucleophilic additions, [4 + 2] cycloadditions, ATP-dependent heterocyclisation to form thiazolines or oxazolines, and radical-mediated reactions between unactivated carbons. Future prospects for RiPP pathway discovery and characterisation will also be highlighted. PMID- 27559379 TI - Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides. AB - Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4 phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. PMID- 27559381 TI - On the mechanism of imine elimination from Fischer tungsten carbene complexes. AB - (Aminoferrocenyl)(ferrocenyl)carbene(pentacarbonyl)tungsten(0) (CO)5W=C(NHFc)Fc (W(CO) 5 ( E -2)) is synthesized by nucleophilic substitution of the ethoxy group of (CO)5W=C(OEt)Fc (M(CO) 5 (1 (Et) )) by ferrocenyl amide Fc-NH(-) (Fc = ferrocenyl). W(CO) 5 ( E -2) thermally and photochemically eliminates bulky E-1,2 diferrocenylimine ( E -3) via a formal 1,2-H shift from the N to the carbene C atom. Kinetic and mechanistic studies to the formation of imine E -3 are performed by NMR, IR and UV-vis spectroscopy and liquid injection field desorption ionization (LIFDI) mass spectrometry as well as by trapping experiments for low-coordinate tungsten complexes with triphenylphosphane. W(CO) 5 ( E -2) decays thermally in a first-order rate-law with a Gibbs free energy of activation of DeltaG (?) 298K = 112 kJ mol(-1). Three proposed mechanistic pathways are taken into account and supported by detailed (time-dependent) densitiy functional theory [(TD)-DFT] calculations. The preferred pathway is initiated by an irreversible CO dissociation, followed by an oxidative addition/pseudorotation/reductive elimination pathway with short-lived, elusive seven-coordinate hydrido tungsten(II) intermediates cis (N,H)-W(CO) 4 (H)( Z -15) and cis (C,H)-W(CO) 4 (H)( Z -15). PMID- 27559380 TI - Artificial Diels-Alderase based on the transmembrane protein FhuA. AB - Copper(I) and copper(II) complexes were covalently linked to an engineered variant of the transmembrane protein Ferric hydroxamate uptake protein component A (FhuA DeltaCVF(tev)). Copper(I) was incorporated using an N-heterocyclic carbene (NHC) ligand equipped with a maleimide group on the side arm at the imidazole nitrogen. Copper(II) was attached by coordination to a terpyridyl ligand. The spacer length was varied in the back of the ligand framework. These biohybrid catalysts were shown to be active in the Diels-Alder reaction of a chalcone derivative with cyclopentadiene to preferentially give the endo product. PMID- 27559382 TI - Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions. AB - Bis-protic N-heterocyclic carbene complexes of platinum and palladium (4) yield dimeric structures 6 when treated with sodium tert-butoxide in CH2Cl2. The use of a more polar solvent (THF) and a strong base (LiN(iPr)2) gave the lithium chloride adducts monobasic complex 7 or analogous dibasic complex 8. PMID- 27559383 TI - Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals. AB - A cooperative catalytic strategy of chiral iminium catalysis by regioselective activation of the C=C bond in enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with alpha,beta-unsaturated aldehydes has been developed. PMID- 27559384 TI - Application of Cu(I)-catalyzed azide-alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA. AB - Efficient protocols based on Cu(I)-catalyzed azide-alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole-imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs. PMID- 27559385 TI - Selective bromochlorination of a homoallylic alcohol for the total synthesis of ( )-anverene. AB - The scope of a recently reported method for the catalytic enantioselective bromochlorination of allylic alcohols is expanded to include a specific homoallylic alcohol. Critical factors for optimization of this reaction are highlighted. The utility of the product bromochloride is demonstrated by the first total synthesis of an antibacterial polyhalogenated monoterpene, (-) anverene. PMID- 27559386 TI - Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates. AB - The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step. PMID- 27559387 TI - Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand-metal interactions. AB - A series of Cr(III) complexes based on quinoline-cyclopentadienyl ligands with additional hemilabile side arms were prepared and used as single-site catalyst precursors for ethylene polymerization. The additional donor functions interact with the metal centers only after activation with the co-catalyst. Evidence for this comes from DFT-calculations and from the differing behavior of the complexes in ethylene polymerization. All complexes investigated show very high catalytic activity and the additional side arm minimizes chain-transfer reactions, leading to increase of molecular weights of the resulting polymers. PMID- 27559388 TI - The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol. AB - Farnesyl diphosphate (FPP) and all fifteen positional isomers of ((13)C1)FPP were enzymatically converted by the bacterial terpene cyclases corvol ether synthase from Kitasatospora setae, the epi-cubebol synthase from Streptosporangium roseum, and the isodauc-8-en-11-ol synthase from Streptomyces venezuelae. The enzyme products were analysed by GC-MS and GC-QTOF MS(2) and the obtained data were used to delineate the EIMS fragmentation mechanisms of the two sesquiterpene ethers corvol ethers A and B, and the sesquiterpene alcohols epi-cubebol and isodauc-8 en-11-ol. PMID- 27559389 TI - From N-vinylpyrrolidone anions to modified paraffin-like oligomers via double alkylation with 1,8-dibromooctane: access to covalent networks and oligomeric amines for dye attachment. AB - The double alkylation of N-vinylpyrrolidone (N-VP) with 1,8-dibromooctane yields paraffin-like oligomeric chains bearing polymerizable vinyl moieties. These oligomers were radically crosslinked in bulk with N-VP as co-monomer yielding swellable polymer disks. The vinylic side groups of the N-VP oligomers allow thiol-ene click reactions with 2-aminoethanethiol hydrochloride to obtain reactive amino-functionalized oligomers. Further modification of the free amino groups with 1,4-difluoro-9,10-anthraquinone (DFA) yields red-colored oligomeric anthraquinone dyes. The final reaction of DFA-substituted N-VP oligomers with Jeffamine((r)) M 600 leads to blue-colored and branched oligomers with poly(ethylene glycol) side chains. PMID- 27559390 TI - 3,6-Carbazole vs 2,7-carbazole: A comparative study of hole-transporting polymeric materials for inorganic-organic hybrid perovskite solar cells. AB - The ever increasing demand for clean energy has encouraged researchers to intensively investigate environmentally friendly photovoltaic devices. Inorganic organic hybrid perovskite solar cells (PSCs) are very promising due to their potentials of easy fabrication processes and high power conversion efficiencies (PCEs). Designing hole-transporting materials (HTMs) is one of the key factors in achieving the high PCEs of PSCs. We now report the synthesis of two types of carbazole-based polymers, namely 3,6-Cbz-EDOT and 2,7-Cbz-EDOT, by Stille polycondensation. Despite the same chemical composition, 3,6-Cbz-EDOT and 2,7-Cbz EDOT displayed different optical and electrochemical properties due to the different connectivity mode of the carbazole unit. Therefore, their performances as hole-transporting polymeric materials in the PSCs were also different. The device based on 2,7-Cbz-EDOT showed better photovoltaic properties with the PCE of 4.47% than that based on 3,6-Cbz-EDOT. This could be due to its more suitable highest occupied molecular orbital (HOMO) level and higher hole mobility. PMID- 27559391 TI - Ring-whizzing in polyene-PtL2 complexes revisited. AB - Ring-whizzing was investigated by hybrid DFT methods in a number of polyene Pt(diphosphinylethane) complexes. The polyenes included cyclopropenium(+), cyclobutadiene, cyclopentadienyl(+), hexafluorobenzene, cycloheptatrienyl(+), cyclooctatetraene, octafluorooctatetraene, 6-radialene, pentalene, phenalenium(+), naphthalene and octafluoronaphthalene. The HOMO of a d(10) ML2 group (with b2 symmetry) interacting with the LUMO of the polyene was used as a model to explain the occurrence of minima and maxima on the potential energy surface. PMID- 27559392 TI - Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides. AB - Ferrocenyl hetaryl thioketones react smoothly with in situ generated thiocarbonyl S-methanides to give 1,3-dithiolanes. In the case of aromatic S-methanides, the sterically more crowded 4,4,5,5-tetrasubstituted 1,3-dithiolanes (2-CH2 isomers) were formed as sole products. The reactions with cycloaliphatic S-methanides led to mixtures of 2-CH2 and 5-CH2 isomers with the major component being the sterically more crowded 2-CH2 isomers. The preferred formation of the latter products is explained by the assumption that the formal [3 + 2]-cycloadducts were formed via a stepwise reaction mechanism with a stabilized 1,5-diradical as a key intermediate. The complete change of the reaction mechanism toward the concerted [3 + 2]-cycloaddition was observed in the reaction of a sterically crowded cycloaliphatic thiocarbonyl ylide with ferrocenyl methyl thioketone. PMID- 27559393 TI - Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells. AB - Pyocyanin is a small molecule produced by Pseudomonas aeruginosa that plays a crucial role in the pathogenesis of infections by this notorious opportunistic pathogen. The inhibition of pyocyanin production has been identified as an attractive antivirulence strategy for the treatment of P. aeruginosa infections. Herein, we report the discovery of an inhibitor of pyocyanin production in cultures of wild-type P. aeruginosa which is based around a 4-alkylquinolin-2(1H) one scaffold. To the best of our knowledge, this is the first reported example of pyocyanin inhibition by a compound based around this molecular framework. The compound may therefore be representative of a new structural sub-class of pyocyanin inhibitors, which could potentially be exploited in in a therapeutic context for the development of critically needed new antipseudomonal agents. In this context, the use of wild-type cells in this study is notable, since the data obtained are of direct relevance to native situations. The compound could also be of value in better elucidating the role of pyocyanin in P. aeruginosa infections. Evidence suggests that the active compound reduces the level of pyocyanin production by inhibiting the cell-cell signalling mechanism known as quorum sensing. This could have interesting implications; quorum sensing regulates a range of additional elements associated with the pathogenicity of P. aeruginosa and there is a wide range of other potential applications where the inhibition of quorum sensing is desirable. PMID- 27559394 TI - Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates. AB - This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyranosides with an elongated hydrophobic hydrocarbon chain. The new N-[6-(beta-D-glucopyranosyloxy)hexyl]ammonium bromides and their O-acetyl derivatives were analyzed via (1)H and (13)C NMR spectroscopy. The mutagenic activity of the newly synthesized QAS was investigated using two different techniques: The Vibrio harveyi luminescence assay and the Ames test. The obtained results support previous findings contesting QAS safety and indicate that QAS, specifically pyridinium derivatives, might be mutagenic. PMID- 27559395 TI - Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen. AB - Vaccines against S. pneumoniae, one of the most prevalent bacterial infections causing severe disease, rely on isolated capsular polysaccharide (CPS) that are conjugated to proteins. Such isolates contain a heterogeneous oligosaccharide mixture of different chain lengths and frame shifts. Access to defined synthetic S. pneumoniae CPS structures is desirable. Known syntheses of S. pneumoniae serotype 3 CPS rely on a time-consuming and low-yielding late-stage oxidation step, or use disaccharide building blocks which limits variability. Herein, we report the first iterative automated glycan assembly (AGA) of a conjugation-ready S. pneumoniae serotype 3 CPS trisaccharide. This oligosaccharide was assembled using a novel glucuronic acid building block to circumvent the need for a late stage oxidation. The introduction of a washing step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides. PMID- 27559396 TI - Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions. AB - Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported. Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. PMID- 27559397 TI - Stereodynamic tetrahydrobiisoindole "NU-BIPHEP(O)"s: functionalization, rotational barriers and non-covalent interactions. AB - Stereodynamic ligands offer intriguing possibilities in enantioselective catalysis. "NU-BIPHEPs" are a class of stereodynamic diphosphine ligands which are easily accessible via rhodium-catalyzed double [2 + 2 + 2] cycloadditions. This study explores the preparation of differently functionalized "NU-BIPHEP(O)" compounds, the characterization of non-covalent adduct formation and the quantification of enantiomerization barriers. In order to explore the possibilities of functionalization, we studied modifications of the ligand backbone, e.g., with 3,5-dichlorobenzoyl chloride. Diastereomeric adducts with Okamoto-type cellulose derivatives and on-column deracemization were realized on the basis of non-covalent interactions. Enantioselective dynamic HPLC (DHPLC) allowed for the determination of rotational barriers of DeltaG (?) 298K = 92.2 +/ 0.3 kJ mol(-1) and 99.5 +/- 0.1 kJ mol(-1) underlining the stereodynamic properties of "NU-BIPHEPs" and "NU-BIPHEP(O)s", respectively. These results make the preparation of tailor-made functionalized stereodynamic ligands possible and give an outline for possible applications in enantioselective catalysis. PMID- 27559398 TI - Star-shaped and linear pi-conjugated oligomers consisting of a tetrathienoanthracene core and multiple diketopyrrolopyrrole arms for organic solar cells. AB - Solution-processable star-shaped and linear pi-conjugated oligomers consisting of an electron-donating tetrathienoanthracene (TTA) core and electron-accepting diketopyrrolopyrrole (DPP) arms, namely, TTA-DPP4 and TTA-DPP2, were designed and synthesized. Based on density functional theory calculations, the star-shaped TTA DPP4 has a larger oscillator strength than the linear TTA-DPP2, and consequently, better photoabsorption property over a wide range of visible wavelengths. The photovoltaic properties of organic solar cells based on TTA-DPP4 and TTA-DPP2 with a fullerene derivative were evaluated by varying the thickness of the bulk heterojunction active layer. As a result of the enhanced visible absorption properties of the star-shaped pi-conjugated structure, better photovoltaic performances were obtained with relatively thin active layers (40-60 nm). PMID- 27559399 TI - The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals. AB - A novel approach to protecting jet fuel against the effects of water contamination is predicated upon the coupling of the rapid hydrolysis reactions of lipophilic cyclic geminal ethers, with the concomitant production of a hydrophilic acyclic hydroxyester with de-icing properties (Fuel Dehydrating Icing Inhibitors - FDII). To this end, a kinetic appraisal of the hydrolysis reactions of representative geminal ethers was undertaken using a convenient surrogate for the fuel-water interface (D2O/CD3CN 1:4). We present here a library of acyclic and five/six-membered cyclic geminal ethers arranged according to their hydroxonium catalytic coefficients for hydrolysis, providing for the first time a framework for the development of FDII. A combination of (1)H NMR, labelling and computational studies was used to assess the effects that may govern the observed relative rates of hydrolyses. PMID- 27559400 TI - Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3 triazoles as IMP/GMP mimics: synthesis and biological evaluation. AB - A series of seventeen beta-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5'-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM. PMID- 27559401 TI - One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three component reaction. AB - A novel three-component reaction has been developed to assemble biologically and pharmaceutically important tetracyclic fused imidazo[1,2-a]pyridines in a one-pot fashion utilizing readily available 2-aminopyridines, isatins and isocyanides. The three-component coupling proceeds through the Groebke-Blackburn-Bienayme reaction followed by a retro-aza-ene reaction and subsequent nucleophilic reaction of the in-situ generated imidazo[1,2-a]pyridines bearing an isocyanate functional group. PMID- 27559402 TI - Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation. AB - A practical method was elaborated for the synthesis of (aminomethylene)bisphosphine oxides comprising the catalyst- and solvent-free microwave-assisted three-component condensation of primary amines, triethyl orthoformate and two equivalents of diphenylphosphine oxide. The method is also suitable for the preparation of (aminomethylene)bisphosphonates using (MeO)2P(O)H/(MeO)3CH or (EtO)2P(O)H/(EtO)3CH reactant pairs and even secondary amines. Several intermediates referring to the reaction mechanism together with a few by-products could also be identified. PMID- 27559403 TI - Flow carbonylation of sterically hindered ortho-substituted iodoarenes. AB - The flow synthesis of ortho-substituted carboxylic acids, using carbon monoxide gas, has been studied for a number of substrates. The optimised conditions make use of a simple catalyst system compromising of triphenylphosphine as the ligand and palladium acetate as the pre-catalyst. Carbon monoxide was introduced via a reverse "tube-in-tube" flow reactor at elevated pressures to give yields of carboxylated products that are much higher than those obtained under normal batch conditions. PMID- 27559406 TI - Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands. AB - A series of methylpalladium(II) complexes with pyrimidine-NHC ligands carrying different aryl- and alkyl substituents R ([((pym)^(NHC-R))Pd(II)(CH3)X] with X = Cl, CF3COO, CH3) has been prepared by transmetalation reactions from the corresponding silver complexes and chloro(methyl)(cyclooctadiene)palladium(II). The dimethyl(1-(2-pyrimidyl)-3-(2,6-diisopropylphenyl)imidazolin-2 ylidene)palladium(II) complex was synthesized via the free carbene route. All complexes were fully characterized by standard methods and in three cases also by a solid state structure. PMID- 27559405 TI - Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts. AB - Chiral binaphthyl-modified squaramide-catalyzed enantioselective addition of diphenyl phosphonate to ketimines derived from isatins has been achieved. This method affords practical and efficient access to chiral 3-amino-3-phosphonyl substituted oxindole derivatives in high yields with excellent enantioselectivities (up to 99% ee). PMID- 27559404 TI - Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides. AB - This review highlights the biosynthesis of heterocycles in polyketide natural products with a focus on oxygen and nitrogen-containing heterocycles with ring sizes between 3 and 6 atoms. Heterocycles are abundant structural elements of natural products from all classes and they often contribute significantly to their biological activity. Progress in recent years has led to a much better understanding of their biosynthesis. In this context, plenty of novel enzymology has been discovered, suggesting that these pathways are an attractive target for future studies. PMID- 27559407 TI - Dinuclear thiazolylidene copper complex as highly active catalyst for azid-alkyne cycloadditions. AB - A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide-alkyne cycloaddition (CuAAC) "click" reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described 1,2,4-triazol-5-ylidene derivatives. Kinetic experiments revealed its high catalytic CuAAC activity in organic solvents at room temperature. The activity increases upon addition of acetic acid, particularly for more acidic alkyne substrates. The modular catalyst design renders possible the exchange of N heterocyclic carbene, linker, sacrificial ligand, and counter ion. PMID- 27559408 TI - A T-shape diphosphinoborane palladium(0) complex. AB - The reaction of CpPd(eta (3) -C3H5) with the new diphosphinoborane ligand derivative (o-PCy2-C6H4)2BPh (Cy) DPB (Ph) affords the T-shape complex ( (Cy) DPB (Ph) )Pd(0) 9, which was characterized by X-ray analysis. PMID- 27559409 TI - One-pot synthesis of 4'-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling. AB - A convenient one-pot approach to alkylcyanobiaryls is described. The method is based on biaryl cross-coupling between the sodium salt of the terephthalonitrile dianion and a neutral aromatic nitrile in liquid ammonia, and successive alkylation of the long-lived anionic intermediate with alkyl bromides. The reaction is compatible with benzonitriles that contain methyl, methoxy and phenyl groups, fluorine atoms, and a 1-cyanonaphthalene residue. The variety of omega substituted alkyl bromides, including an extra bromine atom, a double bond, cyano and ester groups, as well as a 1,3-dioxane fragment are suitable as alkylation reagents. PMID- 27559410 TI - Cp2TiCl/D2O/Mn, a formidable reagent for the deuteration of organic compounds. AB - Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages. PMID- 27559411 TI - On the cause of low thermal stability of ethyl halodiazoacetates. AB - Rates for the thermal decomposition of ethyl halodiazoacetates (halo = Cl, Br, I) have been obtained, and reported herein are their half-lives. The experimental results are supported by DFT calculations, and we provide a possible explanation for the reduced thermal stability of ethyl halodiazoacetates compared to ethyl diazoacetate and for the relative decomposition rates between the chloro, bromo and iodo analogs. We have also briefly studied the thermal, non-catalytic cyclopropanation of styrenes and compared the results to the analogous Rh(II) catalyzed reactions. PMID- 27559412 TI - Catalytic Chan-Lam coupling using a 'tube-in-tube' reactor to deliver molecular oxygen as an oxidant. AB - A flow system to perform Chan-Lam coupling reactions of various amines and arylboronic acids has been realised employing molecular oxygen as an oxidant for the re-oxidation of the copper catalyst enabling a catalytic process. A tube-in tube gas reactor has been used to simplify the delivery of the oxygen accelerating the optimisation phase and allowing easy access to elevated pressures. A small exemplification library of heteroaromatic products has been prepared and the process has been shown to be robust over extended reaction times. PMID- 27559413 TI - Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (+/-)-ezetimibe. AB - An effective synthesis for syn-beta-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium-hydride complex (Rh-H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4-reduction of an alpha,beta-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-beta-lactam. Additionally, the reaction was applied to the synthesis of (+/-)-ezetimibe, a potent beta-lactamic cholesterol absorption inhibitor. PMID- 27559414 TI - Experimental and theoretical insights in the alkene-arene intramolecular pi stacking interaction. AB - Chiral acrylic esters derived from biomass were developed as models to have a better insight in the aryl-vinyl pi-stacking interactions. Quantum chemical calculations, NMR studies and experimental evidences demonstrated the presence of equilibriums of at least four different conformations: pi-stacked and face-to edge, each of them in an s-cis/s-trans conformation. The results show that the stabilization produced by the pi-pi interaction makes the pi-stacked conformation predominant in solution and this stabilization is slightly affected by the electron density of the aromatic counterpart. PMID- 27559415 TI - Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity. AB - The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3 pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds suggests that they could be considered as promising candidates for future developments. PMID- 27559416 TI - Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications. AB - Two high bandgap benzodithiophene-benzotriazole-based polymers were synthesized via palladium-catalysed Stille coupling reaction. In order to compare the effect of the side chains on the opto-electronic and photovoltaic properties of the resulting polymers, the benzodithiophene monomers were substituted with either octylthienyl (PTzBDT-1) or dihexylthienyl (PTzBDT-2) as side groups, while the benzotriazole unit was maintained unaltered. The optical characterization, both in solution and thin-film, indicated that PTzBDT-1 has a red-shifted optical absorption compared to PTzBDT-2, likely due to a more planar conformation of the polymer backbone promoted by the lower content of alkyl side chains. The different aggregation in the solid state also affects the energetic properties of the polymers, resulting in a lower highest occupied molecular orbital (HOMO) for PTzBDT-1 with respect to PTzBDT-2. However, an unexpected behaviour is observed when the two polymers are used as a donor material, in combination with PC61BM as acceptor, in bulk heterojunction solar cells. Even though PTzBDT-1 showed favourable optical and electrochemical properties, the devices based on this polymer present a power conversion efficiency of 3.3%, considerably lower than the efficiency of 4.7% obtained for the analogous solar cells based on PTzBDT-2. The lower performance is presumably attributed to the limited solubility of the PTzBDT-1 in organic solvents resulting in enhanced aggregation and poor intermixing with the acceptor material in the active layer. PMID- 27559417 TI - Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics. AB - The atom-by-atom control provided by synthetic organic chemistry presents a means of generating new functional nanomaterials with great precision. Bringing together these two very disparate skill sets is, however, quite uncommon. This autobiographical review provides some insight into how my program evolved, as well as giving some idea of where we are going. PMID- 27559419 TI - Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu(2.). AB - Functionalization of calix[4]arene with amidofluorene moieties at the lower rim led to formation of the 1,3-diconjugate of calix[4]arene L as a novel fluorescent chemosensor for Cu(2+). The receptor molecule L exhibited a pronounced selectivity towards Cu(2+) over other mono and divalent ions. The formation of the complex between L and Cu(2+) was evaluated by absorption, fluorescence and (1)H NMR spectroscopy. The sensor L showed a remarkable color change from colorless to purple and a fluorescence quenching only upon interaction with Cu(2+). The 1:1 stoichiometry of the obtained complex has been determined by Job's plot. The association constant determined by fluorescence titration was found to be 1.8 * 10(6) M(-1). The sensor showed a linear response toward Cu(2+) in the concentration range from 1 to 10 uM with a detection limit of 9.6 * 10(-8) M. PMID- 27559420 TI - TMSBr-mediated solvent- and work-up-free synthesis of alpha-2-deoxyglycosides from glycals. AB - The thio-additions of glycals were efficiently promoted by a stoichiometric amount of trimethylsilyl bromide (TMSBr) to produce S-2-deoxyglycosides under solvent-free conditions in good to excellent yields. In addition, with triphenylphosphine oxide as an additive, the TMSBr-mediated direct glycosylations of glycals with a large range of alcohols were highly alpha-selective. PMID- 27559421 TI - Synthesis of the C8'-epimeric thymine pyranosyl amino acid core of amipurimycin. AB - The C8'-epimeric pyranosyl amino acid core 2 of amipurimycin was synthesized from D-glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective beta glycosylation afforded the pyranosyl thymine nucleoside 2 - a core of amipurimycin. PMID- 27559418 TI - Rearrangements of organic peroxides and related processes. AB - This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O-O bond cleavage. Detailed information about the Baeyer-Villiger, Criegee, Hock, Kornblum-DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately. PMID- 27559422 TI - Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into beta-functionalized alpha-ketoamides. AB - A sequential three-component process is described, starting from 3-arylmethylene 2,5-piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions. Their transformation into beta-trifluoroacetamido-alpha-ketoamide and alpha,beta-diketoamide frameworks was also achieved in a single step. PMID- 27559423 TI - Cerebellar EBV-associated diffuse large B cell lymphoma following angioimmunoblastic T cell lymphoma. AB - Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disorders may be seen in patients with angioimmunoblastic T cell lymphoma (AITL). Although both nodal and extranodal sites of involvement have been described, central nervous system involvement by B cell lymphoma following AITL has not previously been documented. We report a first example of such unusual presentation, in which an 80-year-old man developed diffuse large B cell lymphoma (DLBCL) in the cerebellum 4 months after the initial diagnosis of AITL. EBV-encoded RNAs were detected in the DLBCL, suggesting that EBV played a pivotal role in the pathogenesis of high grade histologic progression of AITL. The patient survived less than 9 months after his initial diagnosis of AITL. We believe that this case expands the spectrum of extranodal manifestation of EBV-positive B cell lymphoma associated with AITL and illustrates the importance of recognition of this association when encountering unusual central nervous system lesions in patients with known AITL. PMID- 27559424 TI - Suppressed endothelin-1 by anti-VEGF therapy is important for patients with BRVO related macular edema to improve their vision. AB - BACKGROUND: Branch retinal vein occlusion (BRVO) commonly occurs at the arteriovenous crossing in the unilateral eye, and cardiovascular diseases can be risk factors of BRVO. However, the pathomechanism leading to BRVO is not yet clear. In addition to mechanical compression, the vein might locally constrict due to an altered biochemical environment, such as an increase in the concentration of endothelin-1 (ET-1). We evaluated changes in ET-1 following injection of intravitreal bevacizumab (IVB), which is the anti-vascular endothelial growth factor (VEGF) agent with the longest serum half-life, to determine the effect on BRVO-related macular edema. METHODS: Twenty consecutive patients with BRVO-related macular edema (10 males, 10 females; age range 56-83 years) who visited our hospital were included in this prospective study. Visual acuity (VA); central retinal thickness (CRT), determined by macular optical coherence tomography (OCT); and plasma ET-1 levels were obtained before IVB treatment and 1 month later. RESULTS: Patients had hypertension (80 %), dyslipidemia (50 %), diabetes mellitus (35 %), or collagen disease (5 %). Mean CRT was significantly decreased from 673.0 +/- 327.8 to 388.2 +/- 155.0 MUm (P = 0.0007), and mean VA was significantly improved after IVB (P = 0.0239). Mean plasma ET-1 was significantly decreased from 1.272 +/- 0.451 to 1.095 +/- 0.316 pg/mL (P = 0.0238); however, the plasma ET-1 level was increased in all five patients who did not show improved VA after IVB. CONCLUSIONS: In patients with BRVO-related macular edema, anti-VEGF therapy leads to an expected reduction in ET-1 levels; however, the ET-1 level was found to increase in some patients; this is clearly related to less improvement of VA after anti-VEGF therapy. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center UMIN000013236. Registered 10 October, 2012. PMID- 27559425 TI - Nigrosome-1 on Susceptibility Weighted Imaging to Differentiate Parkinson's Disease From Atypical Parkinsonism: An In Vivo and Ex Vivo Pilot Study. AB - BACKGROUND: Previous case-control studies have suggested that the absence of a swallow-tail appearance in the substantia nigra on high-resolution SWI, representing nigrosome-1, has high accuracy to identify Parkinson's disease (PD). The first goal of our study was to evaluate nigrosome-1 ex vivo using optimized high-resolution susceptibility sensitive MRI. Our second goal was to evaluate its diagnostic value in vivo using a clinical 3T SWI sequence to differentiate between PD and atypical parkinsonism (AP) in a cohort of patients with early stage parkinsonism. MATERIAL/METHODS: Case-control pilot study to evaluate nigrosome-1 ex vivo (2 PD, 2 controls), using high-resolution susceptibility sensitive sequences at 11.7 T MRI. Next, evaluation of nigrosome-1 in vivo using a clinical 3 T SWI sequence in a prospective cohort of 60 patients with early stage parkinsonism (39 PD, 21 AP). Moreover, 12 control subjects were scanned. The bilateral substantia nigra was evaluated by two neuroradiologists for the presence, absence or indecisive presence of nigrosome-1. The discriminative power was evaluated by Receiver-Operating Characteristic. RESULTS: We identified nigrosome-1 in ex vivo control subjects. Nigrosome-1 was not identified in the ex vivo PD cases. In our prospective clinical cohort study, the AUC for the swallow tail sign to discriminate between PD and AP was 0.56 (0.41-0.71) for reader 1 and 0.68 (0.55-0.82) for reader 2. CONCLUSIONS: The diagnostic accuracy of the swallow-tail sign was marginal to discriminate between PD and AP using our clinical 3 T SWI sequence. PMID- 27559426 TI - Stent-Assisted Endovascular Treatment of Anterior Communicating Artery Aneurysms Literature Review. AB - The anterior cerebral artery is a common location of intracranial aneurysms. The standard coil embolization technique is limited by its inability to occlude wide neck aneurysms. Stent deployment across the aneurysm neck supports the coil mass inside the aneurysmal sac, and furthermore, has an effect on local hemodynamic and biologic changes. In this article, various management strategies and techniques as well as angiographic outcomes and complications related to stent assisted endovascular treatment of anterior communicating artery aneurysms are presented. This treatment method is safe and associated with low morbidity and mortality rates. PMID- 27559427 TI - Special Issue: Methods for Estimating Treatment Effects for Persons with Multiple Chronic Conditions. PMID- 27559428 TI - A Convex Atomic-Norm Approach to Multiple Sequence Alignment and Motif Discovery. AB - Multiple Sequence Alignment and Motif Discovery, known as NP-hard problems, are two fundamental tasks in Bioinformatics. Existing approaches to these two problems are based on either local search methods such as Expectation Maximization (EM), Gibbs Sampling or greedy heuristic methods. In this work, we develop a convex relaxation approach to both problems based on the recent concept of atomic norm and develop a new algorithm, termed Greedy Direction Method of Multiplier, for solving the convex relaxation with two convex atomic constraints. Experiments show that our convex relaxation approach produces solutions of higher quality than those standard tools widely-used in Bioinformatics community on the Multiple Sequence Alignment and Motif Discovery problems. PMID- 27559429 TI - Complete genome sequence of thermophilic Bacillus smithii type strain DSM 4216(T). AB - Bacillus smithii is a facultatively anaerobic, thermophilic bacterium able to use a variety of sugars that can be derived from lignocellulosic feedstocks. Being genetically accessible, it is a potential new host for biotechnological production of green chemicals from renewable resources. We determined the complete genomic sequence of the B. smithii type strain DSM 4216(T), which consists of a 3,368,778 bp chromosome (GenBank accession number CP012024.1) and a 12,514 bp plasmid (GenBank accession number CP012025.1), together encoding 3880 genes. Genome annotation via RAST was complemented by a protein domain analysis. Some unique features of B. smithii central metabolism in comparison to related organisms included the lack of a standard acetate production pathway with no apparent pyruvate formate lyase, phosphotransacetylase, and acetate kinase genes, while acetate was the second fermentation product. PMID- 27559430 TI - Permanent draft genome of strain ESFC-1: ecological genomics of a newly discovered lineage of filamentous diazotrophic cyanobacteria. AB - The nonheterocystous filamentous cyanobacterium, strain ESFC-1, is a recently described member of the order Oscillatoriales within the Cyanobacteria. ESFC-1 has been shown to be a major diazotroph in the intertidal microbial mat system at Elkhorn Slough, CA, USA. Based on phylogenetic analyses of the 16S RNA gene, ESFC 1 appears to belong to a unique, genus-level divergence; the draft genome sequence of this strain has now been determined. Here we report features of this genome as they relate to the ecological functions and capabilities of strain ESFC 1. The 5,632,035 bp genome sequence encodes 4914 protein-coding genes and 92 RNA genes. One striking feature of this cyanobacterium is the apparent lack of either uptake or bi-directional hydrogenases typically expected within a diazotroph. Additionally, a large genomic island is found that contains numerous low GC content genes and genes related to extracellular polysaccharide production and cell wall synthesis and maintenance. PMID- 27559431 TI - Pancreatic injury in patients with septic shock: A literature review. AB - Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID- 27559432 TI - MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6. AB - AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR 320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection. PMID- 27559433 TI - Opioid-sparing effect of selective cyclooxygenase-2 inhibitors on surgical outcomes after open colorectal surgery within an enhanced recovery after surgery protocol. AB - AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2 (COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery. METHODS: Patients undergoing open colorectal resection within an enhanced recovery after surgery protocol from 2011 to 2015 were reviewed. Patients with combined general anesthesia and epidural anesthesia, and those with acute colonic obstruction or perforation were excluded. Patients receiving selective COX-2 inhibitor were compared with well-matched individuals without such a drug. Outcome measures included numeric pain score and morphine milligram equivalent (MME) consumption on postoperative day (POD) 1-3, gastrointestinal recovery (time to tolerate solid diet and time to defecate), complications and length of postoperative stay. RESULTS: There were 75 patients in each group. Pain score on POD 1-3 was not significantly different between two groups. However, MME consumption and MME consumption per kilogram body weight on POD 1-3 was significantly less in patients receiving a selective COX-2 inhibitor (P < 0.001). Median MME consumption per kilogram body weight on POD 1-3 was 0.09, 0.06 and nil, respectively in patients receiving a selective COX-2 inhibitor and 0.22, 0.25 and 0.07, respectively in the comparative group (P < 0.001), representing at least 59% opioid reduction. Patients prescribing a selective COX-2 inhibitor had a shorter median time to resumption of solid diet [1 (IQR 1-2) d vs 2 (IQR 2-3) d; P < 0.001] and time to first defecation [2 (IQR 2-3) d vs 3 (IQR 3-4) d; P < 0.001]. There was no significant difference in overall postoperative complications between two groups. However, median postoperative stay was significantly 1-d shorter in patients prescribing a selective COX-2 inhibitor [4 (IQR 3-5) d vs 5 (IQR 4-6) d; P < 0.001]. CONCLUSION: Perioperative administration of oral selective COX-2 inhibitors significantly decreased intravenous opioid consumption, shortened time to gastrointestinal recovery and reduced hospital stay after open colorectal surgery. PMID- 27559434 TI - Management of colorectal neoplasia during pregnancy and in the postpartum period. AB - AIM: To report our experience on management of colorectal neoplasia during pregnancy and in the postpartum period. METHODS: Patients who were diagnosed with colorectal cancer during pregnancy or in the postpartum period (< 6 mo), between 8/1997 and 4/2013, in our department were reviewed. Patient characteristics, operations, fetal health and follow-up during pregnancy, type of delivery and oncologic outcomes were analyzed. RESULTS: Eight patients met our study criteria. Median age at the time of diagnosis of colorectal cancer was 31 years. Median follow-up after surgery was 36 mo. Median duration of symptoms before diagnosis was 16 wk. Three patients were diagnosed with colorectal cancer during pregnancy and underwent surgery prior to delivery. None of the patients received adjuvant treatment during pregnancy. Five patients were diagnosed with colorectal cancer within a median of 2.1 mo after delivery and underwent surgery. No adverse neonatal outcomes were noted. All deliveries were at term (2 cesarean sections) except for one preterm delivery following low anterior resection on the 34(th) week of pregnancy. CONCLUSION: There has been a significant delay in the diagnosis of colorectal cancer which is probably due to overlap of symptoms and signs between these tumors and a normal pregnancy. Surgery for colorectal cancer during pregnancy can be performed safely without compromising maternal and fetal outcomes. PMID- 27559435 TI - Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib. AB - AIM: To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). METHODS: Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). RESULTS: The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. CONCLUSION: Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses. PMID- 27559436 TI - Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study. AB - AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last three six months. Values of Malnutrition Universal Screening Tool (MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment (MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index >= 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition (OR = 2.7; 95%CI: 1.2 6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment. PMID- 27559437 TI - Systematic review of laparoscopic vs open surgery for colorectal cancer in elderly patients. AB - AIM: To verify the safety and validity of laparoscopic surgery for the treatment of colorectal cancer in elderly patients. METHODS: A meta-analysis was performed of a systematic search of studies on an electronic database. Studies that compared laparoscopic colectomy (LAC) in elderly colorectal cancer patients with open colectomy (OC) were retrieved, and their short and long-term outcomes compared. Elderly people were defined as 65 years old or more. Inclusion criteria were set at: Resection of colorectal cancer, comparison between laparoscopic and OC and no significant difference in backgrounds between groups. RESULTS: Fifteen studies were identified for analysis. LAC was performed on 1436 patients, and OC performed on 1810 patients. In analyses of short-term outcomes, operation time for LAC was longer than for OC (mean difference = 34.4162, 95%CI: 17.8473 50.9851, P < 0.0001). The following clinical parameters were lower in LAC than in OC: Amount of estimated blood loss (mean difference = -93.3738, 95%CI: -132.3437 to -54.4039, P < 0.0001), overall morbidity (OR = 0.5427, 95%CI: 0.4425-0.6655, P < 0.0001), incisional surgical site infection (OR = 0.6262, 95%CI: 0.4310-0.9097, P = 0.0140), bowel obstruction and ileus (OR = 0.6248, 95%CI: 0.4519-0.8638, P = 0.0044) and cardiovascular complications (OR = 0.4767, 95%CI: 0.2805-0.8101, P = 0.0062). In analyses of long-term outcomes (median follow-up period: 36.4 mo in LAC, 34.3 mo in OC), there was no significant difference in overall survival (mean difference = 0.8321, 95%CI: 0.5331-1.2990, P = 0.4187) and disease specific survival (mean difference = 1.0254, 95%CI: 0.6707-1.5675, P = 0.9209). There was also no significant difference in the number of dissected lymph nodes (mean difference = -0.1360, 95%CI: -4.0553-3.7833, P = 0.9458). CONCLUSION: LAC in elderly colorectal cancer patients had benefits in short-term outcomes compared with OC except operation time. The long-term outcomes and oncological clearance of LAC were similar to that of OC. These results support the assertion that LAC is an effective procedure for elderly patients with colorectal cancer. PMID- 27559438 TI - Transplantation of Neural Stem Cells Cultured in Alginate Scaffold for Spinal Cord Injury in Rats. AB - STUDY DESIGN: This study investigated the effects of transplantation of alginate encapsulated neural stem cells (NSCs) on spinal cord injury in Sprague-Dawley male rats. The neurological functions were assessed for 6 weeks after transplantation along with a histological study and measurement of caspase-3 levels. PURPOSE: The aim of this study was to discover whether NSCs cultured in alginate transplantation improve recovery from spinal cord injury. OVERVIEW OF LITERATURE: Spinal cord injury is one of the leading causes of disability and it has no effective treatment. Spinal cord injury can also cause sensory impairment. With an impetus on using stem cells therapy in various central nervous system settings, there is an interest in using stem cells for addressing spinal cord injury. Neural stem cell is one type of stem cells that is able to differentiate to all three neural lineages and it shows promise in spinal injury treatment. Furthermore, a number of studies have shown that culturing NSCs in three dimensional (3D) scaffolds like alginate could enhance neural differentiation. METHODS: The NSCs were isolated from 14-day-old rat embryos. The isolated NSCs were cultured in growth media containing basic fibroblast growth factor and endothelial growth factor. The cells were characterized by differentiating to three neural lineages and they were cultured in an alginate scaffold. After 7 days the cells were encapsulated and transplanted in a rat model of spinal cord injury. RESULTS: Our data showed that culturing in an alginate 3D scaffold and transplantation of the NSCs could improve neurological outcome in a rat model of spinal cord injury. The inflammation scores and lesion sizes and also the activity of caspase-3 (for apoptosis evaluation) were less in encapsulated neural stem cell transplantation cases. CONCLUSIONS: Transplantation of NSCs that were cultured in an alginate scaffold led to a better clinical and histological outcome for recovery from spinal cord injury in a rat model. PMID- 27559439 TI - Dose Optimization for Single Intradiscal Administration of the Tumor Necrosis Factor-alpha Inhibitor, Etanercept, in Rat Disc Injury Models. AB - STUDY DESIGN: Experimental animal study. PURPOSE: We aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF) alpha inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury. OVERVIEW OF LITERATURE: The pain-related peptide expression was suppressed in the etanercept (100 ug and 1,000 ug)-administered groups in a dose-dependent manner. METHODS: The neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 ug, 100 ug, or 1,000 ug) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups. RESULTS: There were no significant differences between the puncture+saline group and the puncture+10-ug etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double positive cells in FG-positive cells was observed in the etanercept (100 ug and 1,000 ug)-administered groups in a dose-dependent manner (p <0.05). CONCLUSIONS: When a low dose of the TNF-alpha inhibitor (10 ug of etanercept) was directly administered to the rat intervertebral disc in the rat model of degenerative intervertebral disc from injury, no suppressive effect on the pain-related peptide expression was observed. However, when a higher dose of etanercept (100 ug and 1,000 ug) was administered, the pain-related peptide expression was suppressed in a dose-dependent manner. PMID- 27559440 TI - Learning Curve Associated with Complications in Biportal Endoscopic Spinal Surgery: Challenges and Strategies. AB - STUDY DESIGN: Descriptions of technical strategies to overcome pitfalls associated with early learning periods in biportal endoscopic spinal surgery (BESS). PURPOSE: To introduce BESS for lumbar spinal diseases (LSDs) and to inform certain challenges to be overcome in mastering the technique. OVERVIEW OF LITERATURE: BESS has shown superior benefits including excellent magnification, a wider range of view by dynamic handling of an endoscope and instruments. Clinical reports, however, have not yet been very revealing for its new introduction into minimally invasive spine surgery. METHODS: To evaluate the learning curve for BESS, the procedures for various LSDs by one surgeon were analyzed in the view of shortening of the operating times and reduction of complications. Reviewing of recorded procedures helped in finding the reasons and the implemented solutions. RESULTS: The 68 cases included 25 for lumbar disc herniation (LDH), 3 for revision for recurred LDH, 39 for lumbar spinal stenosis (LSS) and 1 for synovial cyst. The operation time for the total cases averaged 83.7+/-33.6 minutes. According to diagnosis, it was 68.2+/-23.7 minutes for LDH. After the 14th case of LDH, it was nearly constant and close to the average time. One level of LSS needed 110.4+/-34.4 minutes. Prolonged operation times even in some later cases of LSS were mainly from struggling against blurred vision due to epidural bleeding. There were 7 cases of complications (10.3%) including 2 cases of dural tear, 1 case of root injury, and 4 cases of incomplete decompression on postoperative magnetic resonance imaging. There was no case of symptomatic hematoma or wound infection. CONCLUSIONS: BESS seemed to have a relatively short learning curve period. The overall complication rate in early learning period was 10.3%. These could be avoided by magnified regional views on an endoscope and a clear surgical field by controlling epidural bleeding. PMID- 27559441 TI - Accuracy of Percutaneous Lumbosacral Pedicle Screw Placement Using the Oblique Fluoroscopic View Based on Computed Tomography Evaluations. AB - STUDY DESIGN: Retrospective. PURPOSE: This study aims to investigate the accuracy of the oblique fluoroscopic view, based on preoperative computed tomography (CT) images for accurate placement of lumbosacral percutaneous pedicle screws (PPS). OVERVIEW OF LITERATURE: Although PPS misplacement has been reported as one of the main complications in minimally invasive spine surgery, there is no comparative data on the misplacement rate among different fluoroscopic techniques, or comparing such techniques with open procedures. METHODS: We retrospectively selected 230 consecutive patients who underwent posterior spinal fusion with a pedicle screw construct for degenerative lumbar disease, and divided them into 3 groups, those who had undergone: minimally invasive percutaneous procedure using biplane (lateral and anterior-posterior views using a single C-arm) fluoroscope views (group M-1), minimally invasive percutaneous procedure using the oblique fluoroscopic view based on preoperative CT (group M-2), and conventional open procedure using a lateral fluoroscopic view (group O: controls). The relative position of the screw to the pedicle was graded for the pedicle breach as no breach, <2 mm, 2-4 mm, or >4 mm. Inaccuracy was calculated and assessed according to the spinal level, direction and neurological deficit. Inter-group radiation exposure was estimated using fluoroscopy time. RESULTS: Inaccuracy involved an incline toward L5, causing medial or lateral perforation of pedicles in group M 1, but it was distributed relatively equally throughout multiple levels in groups M-2 and controls. The mean fluoroscopy time/case ranged from 1.6 to 3.9 minutes. CONCLUSIONS: Minimally invasive lumbosacral PPS placement using the conventional fluoroscopic technique carries an increased risk of inaccurate screw placement and resultant neurological deficits, compared with that of the open procedure. Inaccuracy tended to be distributed between medial and lateral perforations of the L5 pedicle, as a result of pedicle morphology and the PPS pathway. Oblique fluoroscopic views, based on CT measurement, may allow accurate PPS insertion with a shorter fluoroscopy time. PMID- 27559442 TI - Fixation Strength of Caudal Pedicle Screws after Posterior Lumbar Interbody Fusion with the Modified Cortical Bone Trajectory Screw Method. AB - STUDY DESIGN: Clinical case series. PURPOSE: In the posterior lumbar interbody fusion (PLIF) procedure in our institute, the cephalad screw trajectory follows a mediolateral and caudocephalad directed path according to the original cortical bone trajectory (CBT) method. However, the starting point of the caudal screw is at the medial border of the pedicle on an articular surface of the superior articular process, and the trajectory takes a mediolateral path parallel to the cephalad endplate. The incidence of caudal screw loosening after PLIF with this modified CBT screw method was investigated, and significant risk factors for caudal screw loosening were evaluated. OVERVIEW OF LITERATURE: A biomechanical study of this modified caudal screw trajectory using the finite element method reported about a 20% increase in uniaxial yield pullout load compared with the traditional trajectory. However, there has been no clinical study concerning the fixation strength of this modified caudal screw trajectory. METHODS: The subjects were 193 consecutive patients who underwent single-level PLIF with modified CBT screw fixation. Caudal screw loosening was checked in computed tomography at 6 months after surgery, and screw loosening was defined as a radiolucency of 1 mm or more at the bone-screw interface. RESULTS: The incidence of caudal screw loosening after lumbosacral PLIF (46.2%) was significantly higher than that after floating PLIF (6.0%). No significant differences in sex, brand of the instruments, and diameter and length of the caudal screw were evident between patients with and without caudal screw loosening. Patients with caudal screw loosening were significantly older at the time of surgery than patients without caudal screw loosening. CONCLUSIONS: Fixation strength of the caudal screw after floating PLIF with this modified CBT screw technique was sufficiently acceptable. Fixation strength after the lumbosacral procedure was not. PMID- 27559444 TI - Ankylosing Spondylitis: Patterns of Spinal Injury and Treatment Outcomes. AB - STUDY DESIGN: Retrospective review. PURPOSE: We retrospectively reviewed our patients with ankylosing spondylitis (AS) to identify their patterns of spinal fractures to help clarify management strategies and the morbidity and mortality rates associated with this group of patients. OVERVIEW OF LITERATURE: Because of the brittleness of bone and long autofused spinal segments in AS, spinal fractures are common even after minor trauma and often associated with overt instability. METHODS: Between January 1, 1998 and March 2011, 30 patients (23 males, 7 females; mean age, 70.43 years; range, 45 to 95 years) with the radiographic diagnosis of AS of the spinal column had 42 fractures. Eight patients presented with significant trauma, 17 after falls, and 5 after minor falls or no recorded trauma. Eleven patients presented with a neurological injury, ranging from mild sensory loss to quadriplegia. RESULTS: There were 16 compression and 10 transverse fractures, two Jefferson's fractures, one type II and two type III odontoid process fractures, and five fractures of the posterior spinal elements (including lamina and/or facet, three spinous process fractures, three transverse process fractures). Twenty-four fractures affected the craniocervical junction and/or cervical vertebrae, 17 were thoracic, and one involved the lumbar spine. The most affected vertebrae were C6 and T10. The mean follow-up was 29.9 months. One patient was lost to follow-up. Eighteen patients were treated conservatively with bed rest and bracing. Twelve patients underwent surgery for spinal stabilization either with an anterior, posterior or combined approach. CONCLUSIONS: Nonsurgical treatment can be considered especially in the elderly patients with AS and spinal trauma but without instability or major neurological deficits. The nonfusion rate in conservatively treated patients is low. When treatment is selected for patients with spinal fractures and AS, the pattern of injury must be considered and the need for individualized treatment is paramount. PMID- 27559443 TI - Significance of Coronal Proset Magnetic Resonance Imaging to Detect Hidden Zone of the Mid-Zone Stenosis in the Lumbar Spine and Morphometric Analysis of the Mid Zone Stenosis. AB - STUDY DESIGN: Retrospective exploratory imaging study. PURPOSE: To investigate the significance of the coronal magnetic resonance imaging (MRI) using Proset technique to detect the hidden zone in patients with mid-zone stenosis by comparing with conventional axial and sagittal MRI and to explore the morphologic characteristic patterns of the mid-zone stenosis. OVERVIEW OF LITERATURE: Despite advancements in diagnostic modalities such as computed tomography and MRI, stenotic lesions under the pedicle and pars interarticularis, also called the mid zone, are still difficult to definitely detect with the conventional axial and sagittal MRI due to its inherited anatomical peculiarity. METHODS: Of 180 patients scheduled to undergo selective nerve root block, 20 patients with mid zone stenosis were analyzed using MRI. Characteristic group patterns were also explored morphologically by comparing MRI views of each group after verifying statistical differences between them. Hierarchical cluster analysis was performed to classify morphological characteristic groups based on three-dimensional radiologic grade for stenosis at all three zones. RESULTS: At the mid-zone, the stenosis of grade 2 or more was found in 14 cases in the coronal image,13 cases in the sagittal image, and 9 cases in the axial image (p<0.05). Especially, mid zone stenosis was not detected in six of 20 cases at the axial images. At the entrance and exit-zone, coronal image was also associated with more accurate detection of hidden zone compared to other views such as axial and sagittal images. After repeated statistical verification, the morphological patterns of hidden zone were classified into 5 groups: 6 cases in group I; 1 case in group II; 4 cases in group III; 7 cases in group IV; and 2 cases in group V. CONCLUSIONS: Coronal MRI using the Proset technique more accurately detected hidden zone of the mid-zone stenosis compared to conventional axial and sagittal images. PMID- 27559445 TI - Agreement on the Level Selection in Laminoplasty among Experienced Surgeons: A Survey-Based Study. AB - STUDY DESIGN: Survey based study. PURPOSE: To assess the degree of agreement in level selection of laminoplasty (LP) for the selected cervical myeloradiculopathy cases between experienced spine surgeons. OVERVIEW OF LITERATURE: Although, cervical LP is a widely used surgical technique for multi-level spinal cord compression, until now there is no consensus about how many segments or which segments should be opened to achieve a satisfactory decompression. METHODS: Thorough clinical and radiographic data (plain X-ray, computed tomography, and magnetic resonance imaging) of 30 patients who had cervical myelopathy were prepared. The data were provided to three independent spine surgeons with over 10 years experience in operation of their own practices. They were questioned about the most preferable surgical method and suitable decompression levels. The second survey was carried out after 6 months with the same cases. If the level difference between respondents was a half level or below, agreement was considered acceptable. The intraobserver and interobserver agreements in level selection were assessed by kappa statistics. RESULTS: Three respondents selected LP as an option for 6, 8, and 22 cases in the first survey and 10, 21, and 24 cases in the second survey. The reasons for selection of LP were levels of ossification of the posterior longitudinal ligament (p=0.004), segmental kyphotic deformity (p=0.036) and mean compression score (p=0.041). Intraobserver agreement showed variable results. Interobserver agreement was poor to fair by perfect matching (kappa=0.111-0.304) and fair to moderate by acceptable matching (kappa=0.308-0.625). CONCLUSIONS: The degree of agreement for level selection of LP was not high even though experienced surgeons would choose the opening segments on the basis of same criteria. These results suggest that more specific guidelines in determination of levels for LP should be required to decrease unnecessary wide decompression according to individual variance. PMID- 27559447 TI - Neglected Thoraco Lumbar Traumatic Spine Injuries. AB - STUDY DESIGN: Retrospective study. PURPOSE: To outline the etiology, complications and management difficulties encountered in the management of neglected thoracolumbar spine injuries. OVERVIEW OF LITERATURE: The English literature describes overlooked diagnosis as the most common cause of neglected spine injuries. However, the reasons differ in developing or under-developed nations. Moreover, there is scarcity of literature about the neglected spinal injuries. METHODS: Patients presenting with thoracolumbar traumatic injuries who had not received any form of treatment for more than three weeks were included in the study. The demographic details, operative procedure performed and complications encountered, along with American Spinal Injury Association grade and spinal cord independence measure score recorded on the history sheets were noted. The data were analyzed. RESULTS: Forty patients were included in the study. Inadequate treatment at the first contact hospital (45%) followed by late presentation (38%) and missed injury (17%) were the major etiological factors for the neglected traumatic injuries in the thoracolumbar spine. The most common complications seen in the management of these cases were pressure sores (58%), back pain (57%), urinary tract infection (42%) and residual kyphotic deformity (42%). CONCLUSIONS: Management of neglected thoracolumbar injuries is challenging. The delay in presentation should not prevent spine surgeon in proceeding with operative intervention as good results can be expected. PMID- 27559446 TI - Transforaminal Percutaneous Endoscopic Discectomy for Lumbar Disc Herniation in Parkinson's Disease: A Case-Control Study. AB - STUDY DESIGN: A case-control study. PURPOSE: To investigate the effectiveness of transforaminal percutaneous endoscopic discectomy (TPED) in Parkinson's disease (PD). OVERVIEW OF LITERATURE: Patients with PD frequently suffer from radiculopathy and low back pain. Additionally, they demonstrate higher complication rates after open spine surgery. However, the clinical outcome of minimally invasive techniques for lumbar discectomy, such as TPED, have not been established for this population. METHODS: Patients diagnosed with lumbar disc hernia were divided into Group A (11 patients diagnosed with PD), and Group B (10 patients as the control, non-PD group). All patients underwent TPED. Indexes of visual analogue scale (VAS) for leg pain and Oswestry disability index (ODI) were assessed right before surgery and at six weeks, three months, six months and one year post-surgery. RESULTS: At the baseline visit, groups did not differ significantly with age (p=0.724), gender (p=0.835), level of operation (p=0.407), ODI (p=0.497) and VAS (p=0.772). Parkinson's patients had higher scores in ODI at every visit, but the outcome was statistically significant only at 3 months (p=0.004) and one year (p=0.007). Similarly, VAS measurements were higher at each time point, with the difference being significant at 3 (p<0.001), 6 (0.021), and 12 (p<0.001) months after surgery. At the end of a year of follow up, ODI was reduced by 49.6% (+/-16.7) in Group A and 59.2% (+/-8.0) in Group B (p=0.111), translating to a 79.5% (+/-13.0) and 91.5% (+/-4.1) average improvement in daily functionality (p=0.024). VAS was reduced by 59.1 mm (+/-11.8) in Group A and 62.2 mm (+/-7.4) in Group B (p=0.485), leading to an 85.3 % (+/-4.0) and 91.9% (+/ 2.6) general improvement in leg pain (p<0.001). CONCLUSIONS: Our data indicate that TPED led to satisfactory improvement in leg pain and daily living in PD patients a year after surgery. PMID- 27559448 TI - Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain. AB - STUDY DESIGN: Retrospective study. PURPOSE: To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. OVERVIEW OF LITERATURE: Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. METHODS: Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. RESULTS: No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). CONCLUSIONS: Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain. PMID- 27559449 TI - Work-Related Low Back Pain Treatment: A Randomized Controlled Trial from Tehran, Iran, Comparing Multidisciplinary Educational Program versus Physiotherapy Education. AB - STUDY DESIGN: Clinical trial. PURPOSE: To compare the multidisciplinary educational program versus physiotherapy education among Iranian nurses. OVERVIEW OF LITERATURE: Low back pain (LBP) can accompany significant occupational injuries in the nursing profession. There is no agreement on the most effective educational practice. METHODS: This study was conducted from August 17, 2014 to September 22, 2014 in Tehran, Iran. Eligible nurses with chronic mechanical LBP (n=136) were classified into an intervention group (n=66) or the control group (n=70). The intervention group received physiotherapy education for 120-minutes followed by a 120-minute health education session based on predictive constructs of social cognitive theory (SCT). The control group received the 120-minute physiotherapy education. Disability rate, pain severity and back pain prevention behavior were measured at initially and 3 months after intervention using visual analogue scale, Roland-Morris disability questionnaire and nursing low back pain preventive behaviors questionnaire. RESULTS: The two groups were the same in terms of all studied variables at the initiation of the study. At the 3-month follow up, predictive constructs of LBP preventive behaviors of participants in the intervention were improved (p<0.001). Significant decreases were evident at 3 months in pain severity (p=0.03) and disability (p=0.003). CONCLUSIONS: The designed multidisciplinary educational intervention could decrease chronic mechanical LBP in nurses. PMID- 27559450 TI - Development and Psychometric Evaluation of Nursing Low Back Pain Predictor Questionnaire Focusing on Nurses Suffering from Chronic Low Back Pain in Iran. AB - STUDY DESIGN: Development and psychometric evaluation. PURPOSE: Design and psychometric assessment of the Nursing Low Back Pain Predictor Questionnaire addressing nurses suffering from chronic low back pain in Iran. OVERVIEW OF LITERATURE: Low back pain is the most prevalent behavior-related health problem among nurses, and it needs to be assessed through a validated multi-factorial questionnaire, using the premises of the social cognitive theory. METHODS: This was a cross-sectional study carried out in Tehran, Iran from April 17, 2014 to July 16, 2014. A 50-item questionnaire based on the social cognitive theory was generated. The questionnaire was distributed among 500 nurses working in hospitals located in different geographically areas in Tehran. Exploratory factor analysis was used to determine the factors and their related items. Cronbach's alpha was calculated to assess reliability. RESULTS: The exploratory factor analysis loaded six factors, named observational learning, outcome expectations, self-efficacy, self-regulation, and self-efficacy in overcoming impediments in the working environment and emotional coping. All factors were jointly accounted for 67.12% of behavior change variance. The Cronbach's alpha coefficient showed excellent internal consistency (alpha=0.91). Test and retest analysis with 2-week intervals indicated an appropriate stability for the questionnaire (intraclass correlation coefficient=0.94). CONCLUSIONS: According the results, the developed questionnaire is a reliable and validated theory-based instrument, which can be used to predict the work, related factors for low back pain among nurses. PMID- 27559451 TI - Quantitative Anatomy of C7 Vertebra in Southern Chinese for Insertion of Lateral Mass Screws and Pedicle Screws. AB - STUDY DESIGN: Retrospective study. PURPOSE: To analyze the quantitative anatomy of C7 vertebra for insertion of lateral mass screws and pedicle screws in Southern Chinese patients. OVERVIEW OF LITERATURE: C7 lateral mass is smaller when compared to other subaxial cervical levels, which limits the length of lateral mass screws that can be used. Some studies have suggested pedicle screws for better fixation. But, this option is limited by the narrow pedicle width. METHODS: We have obtained computed tomography (CT) cervical spine data in 0.625 mm slices from our radiology department. The patients were adults. CTs were from May to August, 2015. The lateral mass screw length was measured using Margerl's technique and pedicle width and pedicle screw trajectory were determined in three dimensional reformated images. RESULTS: CT scans of cervical spines of 94 patients were obtained and 188 lateral masses and pedicles of C7 vertebrae were measured. The mean lateral mass screw length was 13.2 mm (standard deviation [SD] 1.6 mm), mean outer pedicle width was 5.9 mm (SD 1.0 mm) and mean pedicle screw trajectory was 29.4 degrees (SD 3.6 degrees). Most (91.0%) of the pedicles had an outer diameter >=4.5 mm. CONCLUSIONS: The mean lateral mass screw length was longer when compared with other similar studies, while the mean outer pedicle width was narrower. Nearly 10% of the pedicles were unable to accommodate 3.5 mm screws. These findings favor the use of lateral mass screws to provide a safe and stable fixation for C7 vertebrae in Southern Chinese patients, while the final choice of fixation method should only be confirmed after careful preoperative planning with CT scan. PMID- 27559452 TI - Variation in Outcome in Tethered Cord Syndrome. AB - STUDY DESIGN: Fifty patients surgically treated for tethered cord syndrome (TCS) were retrospectively studied at Liaquat National Hospital, Karachi from 2010 until 2014. PURPOSE: To assess the common presentations of TCS in our part of the world and the surgical outcome of the different presentations. OVERVIEW OF LITERATURE: TCS is a stretch-induced functional disorder of the spinal cord with its caudal part anchored by an inelastic structure, which results in characteristic symptoms and signs. Due to the variety of lesions and clinical presentations and the absence of high-quality clinical outcome data, the decision regarding treatment is difficult. METHODS: Fifty consecutive patients with TCS were reviewed retrospectively with a follow-up period of 12-48 months. The majority of the patients were 0-15 years of age with the mean age of 4 years. The presenting complaints and the associated pathologies were documented, and the patients were assessed using the new Karachi TCS severity scale for clinical assessment. RESULTS: Eighty five percent of the patients with thickened filum terminale improved. Sixty six percent of the patients with diastematomyelia, 60% with lipoma and only 46% with myelomeningocele showed clinical improvement postoperatively. Sixty two percent of the patients who presented with paraperesis improved following surgery while 37% remained stable and only one patient deteriorated. Back and leg pain improved in 93% of patients and 50% of patients with urinary impairment improved. CONCLUSIONS: Outcome of patients with TCS varies according to pathology and severity of symptoms. Diastematomyelia and thickened filum had the best outcome. The Karachi TCS severity scale is a valid tool for future studies. PMID- 27559453 TI - An Outcome Measure of Functionality and Pain in Patients with Low Back Disorder: A Validation Study of the Iranian version of Low Back Outcome Score. AB - STUDY DESIGN: Cross-sectional study. PURPOSE: This study aimed to cross culturally translate and validate the low back outcome score (LBOS) in Iran. OVERVIEW OF LITERATURE: Lumbar disc hernia (LDH) is the most common diagnoses of low back pain and imposes a heavy burden on both individual and society. Instruments measuring patient reported outcomes should satisfy cetain psychometric properties. METHODS: The translation and cross-cultural adaptation of the original questionnaire was performed using Beaton's guideline. A total of 163 patients with LDH were asked to respond to the questionnaire at three points in time: preoperative and twice within 1-week interval after surgery assessments. The Oswestry disabilty index (ODI) was also completed. The internal consistency, test-retest, convergent validity, and responsiveness to change were assessed. Responsiveness to change also was assessed comparing patients' pre- and postoperative scores. RESULTS: The mean age of the cohort was 49.8 years (standard deviation=10.1). The Cronbach's alpha coefficients for the LBOS at preoperative and postoperative assessments ranged from 0.77 to 0.79, indicating good internal consistency. Test-retest reliability as performed by intraclass correlation coefficient was found to be 0.82 (0.62-0.91). The instrument discriminated well between sub-groups of patients who differed in the Finneson Cooper score. The ODI correlated strongly with the LBOS score, lending support to its good convergent validity (r=--0.83; p<0.001). Further analysis also indicated that the questionnaire was responsive to change (p<0.001). CONCLUSIONS: The Iranian version of LBOS performed well and the findings suggest that it is a valid measure of back pain treatment evaluation among LDH patients. PMID- 27559454 TI - Postoperative Severe Headache Following Cervical Posterior Surgical Fixation from C2 Distally. AB - STUDY DESIGN: Retrospective study. PURPOSE: To identify the prevalence of severe headache occurring after cervical posterior surgical fixation (PSF) and to evaluate the clinical and radiological findings associated with severe headache after surgery. OVERVIEW OF LITERATURE: Several studies have reported on the axial pain after cervical surgery. However, to our knowledge, the incidence of severe headache after cervical PSF has not been elucidated. METHODS: The medical records and radiological assessment of patients who underwent surgical treatment from August 2002 to May 2012 were reviewed to identify the prevalence and risk factors for severe headaches occurring following PSF from C2 distally. Neck disability index scores (NDI) (the item for neck pain), the type of C2 screw, number of cervical fused levels (1-6), and smoking habit were calculated preoperatively and postoperatively. In addition, radiological parameters (T1 slope angle, C1/2 angle, C2-7 Cobb angle, C2-7 sagittal vertical axis and C1-implant distance) were assessed for all patients. Severe headache was defined as a high NDI headache score (>4 out of 5). RESULTS: Eighty-two patients met the inclusion criteria. The mean age was 59.2 years (range, 21-78 years), and the mean number of fused levels was 5.1. The mean follow-up period was 2.9 years (range, 1-10.9 years). While only one severe headache occurred de novo postoperatively in a patient in the C3 or C4 distally group (total 30 patients, average age of 50.2 years), 11 patients in the C2 distally group (p=0.04) had severe headache occur postoperatively. The radiological parameters were not significantly different between the postoperative milder headache and severe headache (SH) groups. The SH group had a significantly higher preoperative NDI score (neck pain) (p<0.01). CONCLUSIONS: Newly occurring severe headaches can occur in 18% of patients after PSF from C2 distally. The patients with newly occurring severe headaches had significantly higher preoperative NDI score (neck pain). PMID- 27559455 TI - Comparison of Magnetic Resonance Imaging Findings between Pathologically Proven Cases of Atypical Tubercular Spine and Tumour Metastasis: A Retrospective Study in 40 Patients. AB - STUDY DESIGN: Retrospective study. PURPOSE: To note the magnetic resonance imaging (MRI) differences between pathologically proven cases of atypical spinal tuberculosis and spinal metastasis in 40 cases. OVERVIEW OF LITERATURE: Spinal tuberculosis, or Pott's spine, constitutes less than 1% of all cases of tuberculosis and can be associated with a neurologic deficit. Breast, prostate and lung cancer are responsible for more than 80% of metastatic bone disease cases, and spine is the most common site of bone metastasis. Thus, early diagnosis and prompt management of these pathologies are essential in preventing various complications. METHODS: We retrospectively reviewed 40 cases of atypical tuberculosis and metastasis affecting the spine from the year 2012 to 2014, with 20 cases each that were proven by histopathological examination. MR imaging was performed on 1.5 T MR-Scanner (Magnetom Avanto, Siemens) utilizing standard surface coils of spine with contrast injection. Chi-square test was used for determining the statistical significance and p-values were calculated. RESULTS: The most common site of involvement was the thoracic spine, seen in 85% cases of metastasis and 65% cases of Pott's spine (p=0.144). The mean age of patients with tubercular spine was found to be 40 years and that of metastatic spine was 56 years. The following MR imaging findings showed statistical significance (p<0.05): combined vertebral body and posterior elements involvement, skip lesions, solitary lesion, intra-spinal lesions, concentric collapse, abscess formation and syrinx formation. CONCLUSIONS: Tuberculosis should be considered in the differential diagnosis of various spinal lesions including metastasis, fungal spondylodiskitis, sarcoidosis and lymphoma, particularly in endemic countries. Spinal tuberculosis is considered one of the great mimickers of disease as it could present in a variety of typical and atypical patterns, so proper imaging must be performed in order to facilitate appropriate treatment. PMID- 27559456 TI - Postoperative Increase in Occiput-C2 Angle Negatively Impacts Subaxial Lordosis after Occipito-Upper Cervical Posterior Fusion Surgery. AB - STUDY DESIGN: Retrospective case series. PURPOSE: To elucidate the impact of postoperative occiput-C2 (O-C2) angle change on subaxial cervical alignment. OVERVIEW OF LITERATURE: In the case of occipito-upper cervical fixation surgery, it is recommended that the O-C2 angle should be set larger than the preoperative value postoperatively. METHODS: The present study included 17 patients who underwent occipito-upper cervical spine (above C4) posterior fixation surgery for atlantoaxial subluxation of various etiologies. Plain lateral cervical radiographs in a neutral position at standing were obtained and the O-C2 angle and subaxial lordosis angle (the angle between the endplates of the lowest instrumented vertebra (LIV) and C7 vertebrae) were measured preoperatively and postoperatively soon after surgery and ambulation and at the final follow-up visit. RESULTS: There was a significant negative correlation between the average postoperative alteration of O-C2 angle (DO-C2) and the average postoperative alteration of subaxial lordosis angle (Dsubaxial lordosis angle) (r=-0.47, p=0.03). CONCLUSIONS: There was a negative correlation between DO-C2 and Dsubaxial lordosis angles. This suggests that decrease of mid-to lower-cervical lordosis acts as a compensatory mechanism for lordotic correction between the occiput and C2. In occipito-cervical fusion surgery, care must be taken to avoid excessive O-C2 angle correction because it might induce mid-to-lower cervical compensatory decrease of lordosis. PMID- 27559457 TI - Clinical Factors for Prognosis and Treatment Guidance of Spinal Cord Astrocytoma. AB - STUDY DESIGN: Retrospective study. PURPOSE: To obtain information useful in establishing treatment guidelines by evaluating baseline clinical features and treatment outcomes of patients with spinal cord astrocytoma (SCA). OVERVIEW OF LITERATURE: The optimal management of SCA remains controversial, and there are no standard guidelines. METHODS: The study included 20 patients with low-grade and 13 with high-grade SCA surgically treated between 1989 and 2014. Patients were classified according to the extent of surgical resection. Survival was assessed using Kaplan-Meier plots and compared between groups by log-rank tests. Neurological status was defined by the modified McCormick scale and compared between groups by Mann-Whitney U tests. RESULTS: Surgical resection was performed for 19 of 20 low-grade (95%) and 10 of 13 high-grade (76.9%) SCA patients. Only nine patients (27.3%) underwent gross total resection, all of whom had low-grade SCA. Of all patients, 51.5% showed deteriorated neurological status compared to preoperative baseline. Median overall survival was significantly longer for low grade SCA than that (91 months, 78% at 5 years vs. 15 months, 31% at 5 years; p=0.007). Low-grade SCA patients benefited from more aggressive resection, whereas high-grade SCA patients did not. Multivariate analysis revealed histology status (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.09-0.98; p<0.05) and postoperative neurological status (HR, 0.12; CI, 0.02-0.95; p<0.05) as independent predictors of longer overall survival. Adjuvant radiotherapy had no significant impact on survival rate. However, a trend for increased survival was observed with radiation cordotomy (RCT) in high-grade SCA patients. CONCLUSIONS: Aggressive resection for low-grade and RCT may prolong survival. Preservation of neurological status is an important treatment goal. Given the low incidence of SCA, establishing strong collaborative, interdisciplinary, and multi institutional study groups is necessary to define optimal treatments. PMID- 27559458 TI - Clinical Presentation of Cervical Myelopathy at C1-2 Level. AB - STUDY DESIGN: Single-center retrospective study. PURPOSE: To clarify the clinical features of cervical myelopathy at the C1-2 level. OVERVIEW OF LITERATURE: Methods for distinguishing the affected level based on myelomere symptoms or dysfunction of the conducting pathway were established. However, no symptoms have been identified as being specific to the C1-2 level segment. METHODS: We evaluated 24 patients with cervical myelopathy due to spinal cord compression at the C1-2 level. Preoperative neurological assessment were investigated and compared with the rate and site of compression of the spinal cord using computed tomography-myelography. RESULTS: Impaired temperature and pain sensation were confirmed in 18 of the 24 patients with that localized to the upper arms (n=3), forearm (n=9), both (n=2), and whole body (n=4). Muscle weakness was observed in 18 patients, muscle weakness extended from the biceps brachii to the abductor digiti minimi in 10 patients, and in the whole body in 8 patients. Deep tendon reflexes were normal in 10 patients, whereas hyperactive deep tendon reflexes were noted in 14 patients. The rate of spinal cord compression was significantly higher in patients with perceptual dysfunction and muscle weakness compared with those with no dysfunction. However, no significant difference in the rate and site of compression was identified in those with dysfunction. CONCLUSIONS: Perceptual dysfunction and muscle weakness localized to the upper limbs was observed in 58% and 42% of patients, respectively. Neurological abnormalities, such as perceptual dysfunction and muscle weakness, were visualized in patients with marked compression. PMID- 27559459 TI - Vacuum Phenomenon of the Sacroiliac Joint: Correlation with Sacropelvic Morphology. AB - STUDY DESIGN: A radiologic study of sacropelvic morphology and vacuum phenomenon of sacroiliac joint in subjects unrelated to low back pain. PURPOSE: The aim of this study is to describe the relationship between sacropelvic morphology and vacuum phenomenon of the sacroiliac joint. OVERVIEW OF LITERATURE: Lumbopelvic alignment and sacropelvic morphology are associated with the pathomechanisms of various spinal disorders. The vacuum phenomena of the sacroiliac joint (SJVP) are often observed in clinical practice, but the relationships between these phenomena and sacropelvic morphology have not been investigated. This study examined the prevalence of SJVP in computed tomography (CT) images and the relationship between sacropelvic morphology and SJVP. METHODS: We analyzed multiplanar CT images of 93 subjects (59 men, 34 women). Pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) were measured using the three-dimensional reconstruction method. The prevalence of SJVP in multiplanar CT images were reviewed. Roland-Morris Disability Questionnaire (RDQ) scores and the modified Japanese Orthopedic Association (JOA) score, which focuses on subjective symptoms and restriction of activities of daily living, were also obtained from all the subjects. RESULTS: Thirty-six of the 93 subjects had SJVP (39%), with marked female predominance (91% women, 8.5% men). Men with SJVP had significantly lower PI than men without SJVP (35.1 degrees vs. 46.3 degrees , p<0.05). There was no correlation between SJVP and the modified JOA or RDQ scores. CONCLUSIONS: These data suggest that differences in sacropelvic morphology can influence the biomechanical environment and contribute to SJVP in men. Presence of SJVP did not affect JOA or RDQ scores. PMID- 27559460 TI - Novel Foraminal Expansion Technique. AB - The technique we describe was developed for cervical foraminal stenosis for cases in which a keyhole foraminotomy would not be effective. Many cervical stenosis cases are so severe that keyhole foraminotomy is not successful. However, the technique outlined in this study provides adequate enlargement of an entire cervical foraminal diameter. This study reports on a novel foraminal expansion technique. Linear drilling was performed in the middle of the facet joint. A small bone graft was placed between the divided lateral masses after distraction. A lateral mass stabilization was performed with screws and rods following the expansion procedure. A cervical foramen was linearly drilled medially to laterally, then expanded with small bone grafts, and a lateral mass instrumentation was added with surgery. The patient was well after the surgery. The novel foraminal expansion is an effective surgical method for severe foraminal stenosis. PMID- 27559461 TI - Utility of Discography as a Preoperative Diagnostic Tool for Intradural Lumbar Disc Herniation. AB - Preoperative definitive diagnosis of intradural lumbar disc herniation (ILDH) is difficult despite the availability of various neuroradiological investigative tools. We present a case of ILDH diagnosed preoperatively by discography and computed tomography-discography (disco-CT).The patient was a 63-year-old man with acute excruciating right leg pain. Discography and disco-CT demonstrated leakage of the contrast medium into the intradural space. Based on these findings, a right L5 nerve root disturbance caused by ILDH was diagnosed. A right L5 hemi laminectomy and a dorsal durotomy were performed. The herniated disc was carefully dissected and then completely removed. Three months after surgery, the patient had fully recovered. This report highlights the importance of making a definitive diagnosis of ILDH preoperatively for better surgical planning and improved clinical outcomes. Furthermore, discography and disco-CT are both useful preoperative diagnostic tools for the diagnosis of ILDH. PMID- 27559462 TI - Pseudarthrosis of the Cervical Spine: Risk Factors, Diagnosis and Management. AB - Cervical myelopathy and radiculopathy are common pathologies that often improve with spinal decompression and fusion. Postoperative complications include pseudarthrosis, which can be challenging to diagnose and manage. We reviewed the literature with regard to risk factors, diagnosis, controversies, and management of cervical pseudarthrosis. PMID- 27559463 TI - Selective Estrogen Receptor Modulators. AB - Selective estrogen receptor modulators (SERMs) are now being used as a treatment for breast cancer, osteoporosis and postmenopausal symptoms, as these drugs have features that can act as an estrogen agonist and an antagonist, depending on the target tissue. After tamoxifen, raloxifene, lasofoxifene and bazedoxifene SERMs have been developed and used for treatment. The clinically decisive difference among these drugs (i.e., the key difference) is their endometrial safety. Compared to bisphosphonate drug formulations for osteoporosis, SERMs are to be used primarily in postmenopausal women of younger age and are particularly recommended if there is a family history of invasive breast cancer, as their use greatly reduces the incidence of this type of cancer in women. Among the above mentioned SERMs, raloxifene has been widely used in prevention and treatment of postmenopausal osteoporosis and vertebral compression fractures, and clinical studies are now underway to test the comparative advantages of raloxifene with those of bazedoxifene, a more recently developed SERM. Research on a number of adverse side effects of SERM agents is being performed to determine the long-term safety of this class of compouds for treatment of osteoporosis. PMID- 27559464 TI - Management of Tuberculous Infection of the Spine. AB - Spinal tuberculosis accounts for nearly half of all cases of musculoskeletal tuberculosis. It is primarily a medical disease and treatment consists of a multidrug regimen for 9-12 months. Surgery is reserved for select cases of progressive deformity or where neurological deficit is not improved by anti tubercular treatment. Technology refinements and improved surgical expertise have improved the operative treatment of spinal tuberculosis. The infected spine can be approached anteriorly or posteriorly, in a minimally invasive way. We review the various surgical techniques used in the management of spinal tuberculosis with focus on their indications and contraindications. PMID- 27559465 TI - Operative Management of Lumbar Degenerative Disc Disease. AB - Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long term. PMID- 27559466 TI - Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice. AB - BACKGROUND: Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism. METHODS: Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 (-) or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver. RESULTS: Male and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue in line with altered functional and metabolic traits of hyper- and hypothyroidism. CONCLUSIONS: These data demonstrate that the phenotypes of hypo- and hyperthyroidism differ between male and female mice and indicate that sex is an important modifier of phenotypic manifestations. PMID- 27559467 TI - Body mass index and physical activity in early childhood are associated with atopic sensitization, atopic dermatitis and asthma in later childhood. AB - BACKGROUND: The results of studies on the associations of childhood excessive weight/obesity and physical activity with atopic sensitization and atopic diseases are inconsistent. We studied the associations of anthropometry and physical activity in childhood with atopic sensitization and atopic diseases in late childhood. METHODS: In a cohort study including cases exposed to preeclampsia during pregnancy and controls, anthropometry and physical activity were assessed at several ages in 617 children. Associations with atopic sensitization and atopic diseases in late childhood were analysed using multiple logistic regression. RESULTS: Body mass index standard deviation score (BMI SDS) at 1 year and low physical activity at 3-6 years were positively associated with atopic sensitization at 12.8 years [adjusted odds ratio (OR) 1.22; 95 % confidence interval (1.00, 1.49) and OR 2.36; (1.15, 4.81), respectively]. Change in BMI SDS from 1 to 4 years, BMI SDS at 4 years, and high physical activity at 6 10 years were positively associated with atopic dermatitis by 10.8 years [OR 1.46; (1.11, 1.92); OR 1.32; (1.06, 1.65) and OR 1.94; (1.16, 3.24); respectively]. Low physical activity at 3-6 and 6-10 years were positively associated with asthma by 10.8 years [OR 3.61; (1.56, 8.36) and OR 2.52; (1.24, 5.12), respectively]. CONCLUSIONS: BMI and physical activity in early childhood were associated with atopic sensitization, atopic dermatitis and asthma in later childhood. Larger cohorts with repeated measurements of both predictors and outcomes are required to further elucidate this issue. Trial registration Our study was observational without any clinical intervention on the participants. Therefore, no trial registration number is available. PMID- 27559469 TI - Richmond Wellbeing Service Access Strategy for Older Adults. AB - IAPT (Improving Access to Psychological Therapies) is a national programme aimed at increasing availability of evidence based psychological therapies in the NHS. IAPT is primarily for people who have mild to moderate, common mental health difficulties such as depression, anxiety, phobias and post traumatic stress disorder (PTSD). The programme seeks to use the least intrusive method of care possible to treat people at the time when it will be of most help to them. Individuals are able to self-refer into most IAPT services or alternatively can request to be referred by their GP or other services in the community. Richmond Wellbeing Service (RWS) is one such IAPT Service and this research is based on our work to promote accessibility of the service to one of the harder to reach population groups - older adults. We know that IAPT services could have a positive impact on older adults as it is believed on average, 25% of over 65 year olds face common mental health problems. However, only a third of these people discuss this with their GP and so are less likely to be referred to an IAPT Service. In relation to the above, this project was designed to look at increasing access for older adults into Richmond Wellbeing Service (RWS) specifically to improve access to the RWS by older adults by 100. The overall goal was to increase older adult (65+) referral rates by 20% over a year, in raw number this would translate to an increase of 100 over a year period, and in percentage terms an average of 8% of total referrals. Results yielded an increase of 39 referrals between baseline and test period. The majority of this increase had occurred in the final five months of the projects duration(31). Interestingly the number of older adults in the older age band (85+) almost doubled within this period (from 12 to 21). In total, in percentage terms this translates to an an increase of OA referrals from 6% up to 6.7%, as above we are aiming for 8% or an additional increase of 61 patients. Thus during the duration of the project there were signals of an increase in the desired direction, as the number of OA referrals increased following the period of time the interventions were implemented. However referral rates did not fully reach the target set. The authors concluded that sustainable and meaningful change in improving access for older adults into an IAPT service is possible but does take time. (Alongside the increase of referral a continous assessment of quality is required and where neccessary improve upon the appropriateness of the service offered to Older adults). PMID- 27559468 TI - A commentary on the implications of medication prescription rights for the chiropractic profession. AB - There is a growing desire within the chiropractic profession to expand the scope of practice to include limited medication prescription rights for the treatment of spine-related and other musculoskeletal conditions. Such prescribing rights have been successfully incorporated into a number of chiropractic jurisdictions worldwide. If limited to a musculoskeletal scope, medication prescription rights have the potential to change the present role of chiropractors within the healthcare system by paving the way for practitioners to become comprehensive specialists in the conservative management of spine / musculoskeletal disorders. However, if the chiropractic profession wishes to lobby to expand the scope of practice to include limited prescriptive authority, several issues must first be addressed. These would include changes to chiropractic education and legislation, as well as consideration of how such privileges could impact the chiropractic profession on a more theoretical basis. In this commentary, we examine the arguments in favour of and against limited medication prescription rights for chiropractors and discuss the implications of such privileges for the profession. PMID- 27559470 TI - A project to reduce the rate of central line associated bloodstream infection in ICU patients to a target of zero. AB - Central venous catheters (CVCs) are life-saving and the majority of patients in intensive care units (ICUs) have them placed in order to receive medicine and fluids. However, the use of these catheters can result in serious bloodstream infections. The rate of Central Line Associated Blood Stream Infection (CLABSI) in Adult Intensive Care Units (ICUs) at King Abdulaziz Medical City Jeddah (KAMC J) at the start of the project was 2.0/1000 line days in 2008. The Central Line (CL) Bundle by the Institute of Healthcare Improvement (IHI) was implemented at the same time with monitoring of compliance to the CL Bundle. The compliance to CL Bundle was very low at 37% in the same period. A multidisciplinary team was created to improve the compliance to the CL bundle which was expected to have an impact on the rate of CLABSI to achieve zero CLABSI events. The team continued to monitor and evaluate the progress on the compliance to the bundle as well as monitoring the CLABSI events using National Healthcare Safety Network diagnostic criteria. The real reduction in the rate of CLABSI was achieved in 2010 with 0.7/1,000 device days when the compliance to CL Bundle reached up to 98% in that year and 100% in the next two subsequent years. The project still continued and the rate continued to drop and the ultimate target of zero CLABSI was achieved in the year 2014 and maintained in the year 2015 with a sustained compliance of 100% to the CL Bundle. Successful implementation of CL Bundle can help in reducing the rates of CLABSI and achieving zero CLABSI events for a sustained period. PMID- 27559471 TI - Improving Clinical Remission Rates in Pediatric Inflammatory Bowel Disease with Previsit Planning. AB - Inflammatory Bowel Disease (IBD) is a chronic autoimmune inflammatory disease of the intestine which can lead to malnutrition, poor quality of life, and colon cancer.(1-4) Although there is no cure for the disease, clinical remission is the primary goal.(5) The Center for Inflammatory Bowel Disease at MassGeneral Hospital for Children (MGHfC) adopted a Previsit Planning (PVP) model to identify and discuss symptomatic patients prior to their appointments to identify specific issues that impact disease management.(6-8) The Registry from ImproveCareNow (ICN), the international Quality Improvement Collaborative for the management of Crohn's Disease and Ulcerative Colitis in pediatric and adolescent patients, was used to capture information from each ambulatory visit and hospitalization. Using the Model for Improvement framework, the team began a weekly review and made care recommendations of patients with active disease who were cared for by one physician. Interventions were modified over multiple Plan-Do-Study-Act (PDSA) improvement cycles to increase the number of providers and to include patients with mild or moderate disease activity.(9) Feedback from the providers regarding this process was elicited via a REDCap survey and the clinical remission rate was tracked using the ICN Registry. The clinical remission rate for the Center's patients increased from 77% (n=597) in September 2014 to 83% (n=585) in August 2015 and has been maintained. 78% of responding providers indicated that they found the PVP recommendations helpful "all of the time". One hundred percent who responded to the survey said that they have used at least one recommendation provided to them. PVP for management of a chronic disease in pediatrics is feasible, even in a high volume practice. This process at MGHfC has resulted in the improvement of clinical remission rate. PDSA cycles were used to document successes and failures to help guide the work. Ongoing expansion of this PVP practice to all providers continues with the anticipation of including input from patients and their families, as well. PMID- 27559472 TI - Improving pediatric Inflammatory Bowel Disease (IBD) follow-up. AB - Standardization of Inflammatory Bowel Disease (IBD) care through participation in the ImproveCareNow (ICN) Network has improved outcomes for pediatric patients with IBD, but under the current care model, our improvements have plateaued. Current ICN model care guidelines recommend health supervision visits every six months. We identified a gap in our practice's ability to ensure either a routine six month follow-up or a rapid follow-up after a disease flare, and a significant number of patients with active disease status during a six month period lacked timely reassessment after interventions or medication changes. Telemedicine provides an alternative method of care delivery to address these gaps, but has had limited use in patients with IBD. A multi-step approach to offer alternative follow-up care options via telemedicine was developed with potential impact on remission rates and quality of life. Short term goals of the pilot were to improve telemedicine access for patients with IBD were to 1) increase the percent of patients with active disease with a follow-up completed within two months of a visit from 40% to 70%, 2) increase the percent of patients with a visit scheduled within two months of their last sick visit from 20% to 70% (interim measure), 3) increase the number of eVisits from zero visits per month to two visits per month during pilot phase, 4) increase electronic communication with patients from zero messages per month to 200 messages per month, 5) no change in complications or adverse events (defined as an unplanned visit or ED (emergency department) encounter within 30 days of an eVisit. The expected outcomes of the e-visit model were to: maintain baseline care standards and health screening capabilities, improve access to care, and provide equivalent care delivery (no increase in the number of unplanned clinical encounters). Using the IHI model for improvement (Plan-Do-Study-Act) we have seen a progressive increase in the rate of patient signups for the electronic medical record patient portal, with a baseline median of 20% per clinic compared with a current median of approximately 70% after six months. We successfully implemented e-messaging in its pilot form among five providers and have seen steady uptake in patient use from 5 patient initiated messages during the first month to 76 messages/month over the past three months. E-visits have replaced a total of 32 visits to date. Medications, nutrition, and disease activity were appropriately screened and managed electronically without the need for a physical office visit by the treating gastroenterologist. Access to care was improved in that all patients completed their e-visits from their homes without missing school or work and did not require a physical office visit. One visit successfully identified worsening of the patient's clinical course and resulted in a scheduled office visit request, but no unplanned office visits or ED visits have occurred. This report represents the first description of telemedicine use in routine clinical care in children with IBD. We anticipate continuing use of this novel mode of health care delivery in pediatrics in an effort to increase the proportion of patients seen for interval follow-up, after IBD diagnosis, or mild flare in an effort to target early treatment changes that should result in improved remission and patient reported outcomes. E-visits are less expensive and time consuming than traditional visits and may serve as an additional method of cost savings by matching care to a patient's individual needs. PMID- 27559473 TI - Improving the diagnostic quality and adequacy of shoulder radiographs in a District General Hospital. AB - A high rate of suboptimal shoulder radiographs was identified during a service evaluation exercise in our orthopaedic outpatient clinics. Inadequate radiographs require a return to the radiology department for further imaging, a resultant increased workload, delays in the clinic, increased radiation for patients, and inconvenience and decreased patient satisfaction. Furthermore, if a sub-optimal radiograph is accepted there is concern that diagnoses may be missed. The aim of this project was to decrease the rate of suboptimal radiographs by delivering a teaching package directed towards quality improvement. Evaluation criteria were set for standard orthopaedic shoulder radiographs (Anterior-posterior, axillary, and Velpeau views). Baseline data collection was performed over three, two-week periods and included all patients attending the shoulder clinic. The percentage of x-rays which were deemed adequate was only 19.4% for anterior-posterior views and 57.9% for axillary views. A comprehensive educational package was delivered to radiographers. This included a formal PowerPoint based teaching session, hands on training with practice using a skeleton, posters with step-by step instructions on how to obtain an adequate image, and PDF aide memoires suitable for viewing on a smartphone. Two subsequent two-week periods of data collection were performed to evaluate the benefit of this intervention. Delivery of focussed training and provision of easily accessible aide memoires to facilitate improved quality of radiographs resulted in a significant (p<0.05) reduction in the rate of inadequate images. There was also a significant decreases in the rate of return to the radiology department for repeat imaging. PMID- 27559474 TI - Improving physical health monitoring for patients with chronic mental health problems who receive antipsychotic medications. AB - Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service. PMID- 27559475 TI - Improving Door to Needle time in Patients for Thrombolysis. AB - Ischaemic stroke can result in approximately 2 million brain neurones being damaged for each minute that it is left untreated. Various trials and studies such as the National Institute of Neurologic Disorders (NINDS) trial, the European Cooperative Acute Stroke Study (ECASS), ECASS II, and the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study have clearly demonstrated the beneficial effects of intravenous tissue plasminogen activator (tPA) for treatment of acute stroke. Therefore to minimise damage and improve clinical outcome, we need to identify patients who present within 4.5 hours of symptom onset and reduce the time taken to adminster a thrombolytic agent. This time is commonly referred to as the 'door to needle' (DTN) time. Our standard, set by the Clinical Commissioning Group (CCG) is to achieve a median time of scanning and thrombolysis within 55 minutes from the time that the patient enters the hospital. The aim of our QIP was to collect data on what the DTN time was during November 2015, December 2015, and January 2016 and to evaluate how this can be improved after each month. This Quality Improvement Project in the DTN time in patients for thrombolysis has identified areas in the pathway that leads to delays. One major contributing factor is the time for a doctor to come and assess and administer the thrombolytic agent to the patient. Change was implemented by ensuring that the core medical trainee on call is allocated to respond as a priority to all possible thrombolysis calls. This has resulted in a reduction of mean DTN time, from 74 minutes in November to 43 minutes in January. As well as improving patient outcomes, it is proposed that the implementation of change has benefitted the training experience and development of key skills of the core medical trainees. PMID- 27559476 TI - Reducing inpatient falls in a 100% single room elderly care environment: evaluation of the impact of a systematic nurse training programme on falls risk assessment (FRA). AB - Inpatient falls (IF) are the most commonly reported safety incidents. The high rate of inpatient falls was reported in a newly built hospital, within Aneurin Bevan University Health Board, Wales (UK). The aim of the project is to reduce the incidence of IF and associated adverse clinical outcomes in a hospital with 100% single rooms. The key mechanism for improvement was education and training of nursing staff around falls risk factors. A Plan-Do-Study-Act methodology was used and a geriatrician-led, systematic nurse training programme on the understanding and correct use of existing multifactorial falls risk assessment (FRA) tool was implemented in April 2013. Pre-training baseline data revealed inadequate falls assessment and low completion rates of the FRA tool. Subsequent, post-training data showed improvement in compliance with all aspects of FRA. Concurrent with nurse training, the actual falls incidence/1000 patient-bed-days fell significantly from the baseline of 18.19+/-3.46 (Nov 2011-March 2013) to 13.36+/-2.89 (p<0.001) over next 12 months (April 2013-March 2014) and remained low (mean falls 12.81+/-2.85) until November 2015. Improved clinical outcomes have been observed in terms of a reduction of length of stay and new care home placements, making total annualised savings of L642,055. PMID- 27559477 TI - Anticoagulated patient's perception of their illness, their beliefs about the anticoagulant therapy prescribed and the relationship with adherence: impact of novel oral anticoagulant therapy - study protocol for The Switching Study: a prospective cohort study. AB - BACKGROUND: Anticoagulant therapy is prescribed for millions of patients worldwide for the prevention and treatment of both arterial and venous thrombosis. Historically, only vitamin K antagonists have been available for clinicians to prescribe. The anticoagulation landscape is changing. The recent availability of the novel oral anticoagulants overcome many of the disadvantages associated with vitamin K antagonists. However the lack of formal monitoring and clinic follow-up is a concern for clinicians, as medication adherence is being assumed, which is known to decline in patients prescribed medications for chronic conditions. The switching study is a programme of work investigating the association between medication adherence and patient's beliefs about anticoagulation therapy (warfarin and subsequently novel oral anticoagulants), together with beliefs about their illness and anticoagulation related quality of life. METHODS/DESIGN: The anticoagulation database at King's College Hospital will be interrogated and two groups of patients will be identified; those with a time in therapeutic range on warfarin of >=75 % and those <50 %. These groups of patients will have their illness perceptions, anticoagulation specific quality of life and beliefs about medications compared. Those patients in the time in therapeutic range <50 % group, will be then be invited to switch to a novel oral anticoagulant, as per local guidance. Those patients, who do switch, will then be followed longitudinally and have their adherence, illness perceptions, anticoagulation specific quality of life and beliefs about medications, re evaluated on the novel agent. The results from these sub-studies, will inform a clinical pathway to support patients on these novel agents, which will be evaluated in an independent group of patients. DISCUSSION: The results from the switching study will be used to develop a clinical pathway to support patient's prescribed novel oral anticoagulant therapy long-term. PMID- 27559479 TI - Predictors of the therapeutic effect of sivelestat in patients with acute lung injury associated with systemic inflammatory response syndrome. AB - BACKGROUND: Sivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome. However, sivelestat produced inconsistent therapeutic benefits. This study aimed to identify factors predicting the therapeutic effects of sivelestat. METHODS: We enrolled 53 mechanically ventilated patients who received sivelestat. The patients were classified as effective (n = 28) if they were weaned from the ventilator within 28 days, or as ineffective groups (n = 25). Patient characteristics were compared between these groups and multivariate logistic regression analysis was used to identify predictive factors. A validation study was then conducted in sivelestat-free patients. RESULTS: A high red blood cell count and low hydrogen ion concentration were significantly associated with a higher ventilator weaning rate in patients receiving sivelestat. The validation study revealed that the hydrogen ion concentration value also significantly associated with ventilator weaning in patients who did not receive sivelestat. CONCLUSIONS: Although hydrogen ion concentration was inversely associated with the ventilator weaning rate, it did not predict sivelestat efficacy. This study indicated that acute lung injury patients with a high red blood cell count would derive the most benefit from sivelestat administration. PMID- 27559478 TI - An uncommon complication of atrial fibrillation. AB - Coronary embolism is a well-recognized cause of myocardial infarction. It is often under diagnosed and cardiologists need to be vigilant for this diagnosis. A 77-year-old man presented with chest pain with an ECG showing a new diagnosis of atrial fibrillation. Owing to ongoing chest pain coronary angiography was performed and revealed an acute occlusion of the left circumflex artery with coronary blood flow restored following aspiration of a large red thrombus. Following this the coronary vessel looked smooth with no residual coronary lesions requiring angioplasty or plaque rupture to justify the thrombosis. The clinical picture and angiographic data suggested the coronary embolus was secondary to the newly diagnosed atrial fibrillation. PMID- 27559480 TI - Checklists of Parasites of Farm Fishes of Babylon Province, Iraq. AB - Literature reviews of all references concerning the parasitic fauna of fishes in fish farms of Babylon province, middle of Iraq, showed that a total of 92 valid parasite species are so far known from the common carp (Cyprinus carpio), the grass carp (Ctenopharyngodon idella), and the silver carp (Hypophthalmichthys molitrix) as well as from three freshwater fish species (Carassius auratus, Liza abu, and Heteropneustes fossilis) which were found in some fish farms of the same province. The parasitic fauna included one mastigophoran, three apicomplexans, 13 ciliophorans, five myxozoans, five trematodes, 45 monogeneans, five cestodes, three nematodes, two acanthocephalans, nine arthropods, and one mollusc. The common carp was found to harbour 81 species of parasites, the grass carp 30 species, the silver carp 28 species, L. abu 13 species, C. auratus one species, and H. fossilis one species. A host-parasite list for each fish species was also provided. PMID- 27559481 TI - Protein Quantification by Derivatization-Free High-Performance Liquid Chromatography of Aromatic Amino Acids. AB - Amino acid analysis is considered to be the gold standard for quantitative peptide and protein analysis. Here, we would like to propose a simple HPLC/UV method based on a reversed-phase separation of the aromatic amino acids tyrosine (Tyr), phenylalanine (Phe), and optionally tryptophan (Trp) without any derivatization. The hydrolysis of the proteins and peptides was performed by an accelerated microwave technique, which needs only 30 minutes. Two internal standard compounds, homotyrosine (HTyr) and 4-fluorophenylalanine (FPhe) were used for calibration. The limit of detection (LOD) was estimated to be 0.05 uM (~10 ug/L) for tyrosine and phenylalanine at 215 nm. The LOD for a protein determination was calculated to be below 16 mg/L (~300 ng BSA absolute). Aromatic amino acid analysis (AAAA) offers excellent accuracy and a precision of about 5% relative standard deviation, including the hydrolysis step. The method was validated with certified reference materials (CRM) of amino acids and of a pure protein (bovine serum albumin, BSA). AAAA can be used for the quantification of aromatic amino acids, isolated peptides or proteins, complex peptide or protein samples, such as serum or milk powder, and peptides or proteins immobilized on solid supports. PMID- 27559482 TI - [(18)F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis. AB - Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [(18)F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed. PMID- 27559483 TI - Relationship of Inflammatory Biomarkers with Severity of Peripheral Arterial Disease. AB - Objective. The pentraxin family, including high-sensitivity C-reactive protein (hs-CRP), serum amyloid P (SAP), and pentraxin 3 (PTX3), has been identified as playing a key role in inflammatory reactions such as in atherosclerosis and cardiovascular disease. In this study, we examined the relationship between peripheral arterial disease (PAD) and serum levels of pentraxins. Methods. This study was undertaken via a retrospective review of PAD patients with surgical intervention for lesions of the common femoral artery. We evaluated the preoperative patient conditions, hemodynamic status, such as ankle brachial index (ABI), and clinical ischemic conditions according to Rutherford classification. Preoperatively, we collected blood samples for determining the serum levels of hs CRP, SAP, and PTX3. Results. Twelve PAD patients with common femoral arterial lesions were treated and examined. The hemodynamic severity of PAD was not negatively correlated with hs-CRP, SAP, or PTX3. The clinical severity evaluated by Rutherford classification was significantly positively correlated with the serum level of PTX3 (p = 0.019). Conclusion. We demonstrated that PTX3 might be a better marker of PAD than hs-CRP and SAP. Furthermore, PTX3 might be a prognostic marker to evaluate the severity of PAD. PMID- 27559484 TI - A Rare Case of C2 Sensory Blockade with Preserved Phrenic Nerve Function in an Obstetric Patient. AB - High neuraxial blockade is a serious complication in obstetric patients and requires prompt recognition and management in order to optimize patient outcomes. In cases of high neuroblockade, patients may present with significant hypotension, dyspnea, agitation, difficulty speaking or inability to speak, or even loss of consciousness. We report the unusual presentation of an obstetric patient that remained hemodynamically stable and had the preserved ability to initiate breaths despite sensory blockade up to C2. The presence of differential motor and sensory block documented in this case helped enable the patient to be managed with noninvasive ventilatory support until the high blockade regressed and we are not aware of any other similar reports in literature. PMID- 27559485 TI - Pernicious Anemia with Autoimmune Hemolytic Anemia: A Case Report and Literature Review. AB - Pernicious anemia is a common cause of vitamin B12 deficiency. Here, we discuss a case of a young woman who presented with severe anemia along with a history of iron deficiency anemia. After a review of her clinical presentation and laboratory data, we identified an autoimmune hemolytic anemia and a concomitant pernicious anemia. The concurrence of both these hematological diagnoses in a patient is rare. PMID- 27559486 TI - Effectiveness of Simple Individual Psychoeducation for Bipolar II Disorder. AB - Several studies have proven the effectiveness of psychoeducation in bipolar II disorder patients; however, simpler psychoeducation is needed in daily medical practice. Therefore, we devised a simple individual psychoeducation program, which involved 20-minute sessions spent reading a textbook aloud in the waiting time before examination. Here, we report a successful case of simple individual psychoeducation with a patient with bipolar II disorder, a 64-year-old woman who had misconceptions surrounding her mood due to 24 years of treatment for depression. Her perception of mood state, particularly mixed state, was dramatically changed, and her quality of life was improved after the simple individual psychoeducation. This case suggests that the simple individual psychoeducation could be effective for bipolar II disorder by improving understanding of the disease and by meeting different individual needs. PMID- 27559487 TI - A Unique Presentation of Anti-RNA Polymerase III Positive Systemic Sclerosis Sine Scleroderma. AB - Systemic sclerosis is a rare autoimmune disorder with a wide spectrum of clinical manifestations and a multitude of autoantibodies that are associated with it. In the past several years, advances in serologic testing have led to research indicating important prognostic and phenotypic associations with certain subsets of autoantibodies. In particular, anti-RNA polymerase III (anti-RNAP III) has been associated with diffuse cutaneous disease, scleroderma renal crisis, a temporal relationship with malignancy, myositis, synovitis, joint contractures, and gastric antral vascular ectasia. However, anti-RNAP III has not been associated with systemic sclerosis sine scleroderma. We describe a patient with an atypical presentation of anti-RNAP III positive systemic sclerosis sine scleroderma who presented without the typical features of anti-RNAP III disease. Instead, she presented with critical digital ischemia, pulmonary arterial hypertension, gastroesophageal reflux disease, interstitial lung disease, and no clinically detectable sclerodactyly. PMID- 27559488 TI - Haematochezia from a Splenic Artery Pseudoaneurysm Communicating with Transverse Colon: A Case Report and Literature Review. AB - Splenic artery aneurysms (SAA) are the third most common intra-abdominal aneurysm. Complications include invasion into surrounding structures often in association with preexisting pancreatic disease. We describe an 88-year-old female, with no history of pancreatic disease, referred with lower gastrointestinal bleeding. CT angiography showed a splenic artery pseudoaneurysm with associated collection and fistula to the transverse colon at the level of the splenic flexure. The pseudoaneurysm was embolised endovascularly with metallic microcoils. Rectal bleeding ceased. The patient recovered well and follow-up angiography revealed no persistence of the splenic artery pseudoaneurysm. SAA rupture results in 29%-50% mortality. Experienced centres report success with the endovascular approach in haemodynamically unstable patients, as a bridge to surgery, and even on a background of pancreatic disease. This case highlights the importance of prompt CT angiography, if endoscopy fails to identify a cause of gastrointestinal bleeding. Endovascular embolisation provides a safe and effective alternative to surgery, where anatomical considerations and local expertise permit. PMID- 27559489 TI - Comparison of Modified Cartilage Shield Tympanoplasty with Tympanoplasty Using Temporalis Fascia Only: Retrospective Analysis of 142 Cases. AB - The current study compares outcomes of modified cartilage shield tympanoplasty (CST) with temporalis fascia tympanoplasty in type I procedures in Indian patients. Graft uptake rates are better with the CST technique and hearing results are almost equivalent with both techniques except at 8000 Hz where improvement in hearing was found better with the use of temporalis fascia alone. The CST technique used in the study is unique. PMID- 27559490 TI - Epidemiology of Transfusion Transmitted Infection among Patients with beta Thalassaemia Major in Pakistan. AB - Introduction. Transfusion Transmitted Infections (TTIs) continue to be a major risk in transfusions in many parts of the world. The transfusion-dependent beta thalassaemia patients are particularly at risk of acquiring TTIs. The current study was undertaken to estimate the prevalence of TTIs in transfusion-dependent beta-thalassaemia patients. Material and Methods. A cross-sectional study of 1253 multitransfused thalassaemia major patients was conducted in five different centres of Islamabad, Rawalpindi, and Karachi. The study subjects were screened for HIV, HCV, and HBV. The screening was performed at two centres: Department of Pathology, Shaheed Zulfiqar Ali Bhutto (SZAB) Medical University, and Blood Transfusion Services, Jinnah Postgraduate Medical Centre, from July to December 2015. The confirmatory screening was performed by Chemiluminescent Immunoassay (CLIA). Results. Out of the 1253 multiple transfused patients, 317 (25.3%) were infected with TTIs. HCV was positive in 273 cases (21.7%), HBV in 38 cases (3.0%), and HIV in 6 cases (0.5%). Conclusion. HCV was the leading TTI in multitransfused thalassaemia major patients in the study. Presence of HIV in thalassaemia patients is a recent disturbing development in Pakistan. Improved regulation of blood banks including use of internationally or nationally evaluated kits will bring down the incidence of TTIs in transfusion-dependent beta-thalassaemia patients. More stringent behavioral and serological pretransfusion screening of blood for TTIs must be implemented in blood banks. PMID- 27559492 TI - Patients Diagnosed with Colorectal Cancer in Rural Areas in Arizona Typically Present with Higher Stage Disease. AB - BACKGROUND: Despite the decreasing incidence of colorectal cancer (CRC) over the past three decades disparities remain in its incidence, stage at presentation, and efficiency of staging and treatment between different communities, particularly when comparing urban and rural areas. The aim of the study was to assess disparities that exist in CRC outcomes among urban, international border counties, and non-border counties in Arizona. METHODS: A retrospective analysis of CRC data from the Arizona Cancer Registry was performed. Data obtained included age, sex, ethnicity, tumor grade, and tumor stage. The data was then categorized into three sections: international border counties, urban counties, and rural counties. The outcome measure was stage of CRC at diagnosis. RESULTS: There were a total of 39, 958 reported incident cases of colorectal cancer from 1995-2010. Of the total incident cases, 53.1% were male and the average age at diagnosis was 69.5. 86.6% were white non-Hispanic, 8.37% Hispanic, 2.4% African American, 1.7% Native American and 1% Asian. There was a significant decrease in the incidence of CRC in all counties, 24.08% in border, 22.5% in urban, and 12.3% in rural. Rural counties showed a higher number of observed cases than expected cases of stage 4 CRC and more unknown diagnosis of grade, stage and lymph node assessment as determined by the adjusted residual. CONCLUSION: Patients in rural counties are more likely to present with a higher stage of CRC and are less likely to have their cancer adequately staged. This is likely due to lack of better access to healthcare, lack of awareness and poor education and also inadequate specialists. PMID- 27559491 TI - Overexpression of plastin 3 in Sertoli cells disrupts actin microfilament bundle homeostasis and perturbs the tight junction barrier. AB - Throughout the epithelial cycle of spermatogenesis, actin microfilaments arranged as bundles near the Sertoli cell plasma membrane at the Sertoli cell-cell interface that constitute the blood-testis barrier (BTB) undergo extensive re organization by converting between bundled and unbundled/branched configuration to give plasticity to the F-actin network. This is crucial to accommodate the transport of preleptotene spermatocytes across the BTB. Herein, we sought to examine changes in the actin microfilament organization at the Sertoli cell BTB using an in vitro model since Sertoli cells cultured in vitro is known to establish a functional tight junction (TJ)-permeability barrier that mimics the BTB in vivo. Plastin 3, a known actin microfilament cross-linker and bundling protein, when overexpressed in Sertoli cells using a mammalian expression vector pCI-neo was found to perturb the Sertoli cell TJ-barrier function even though its overexpression increased the overall actin bundling activity in these cells. Furthermore, plastin 3 overexpression also perturbed the localization and distribution of BTB-associated proteins, such as occludin-ZO1 and N-cadherin-beta catenin, this thus destabilized the barrier function. Collectively, these data illustrate that a delicate balance of actin microfilaments between organized in bundles vs. an unbundled/branched configuration is crucial to confer the homeostasis of the BTB and its integrity. PMID- 27559493 TI - Increased Incidence of Early Onset Colorectal Cancer in Arizona: A Comprehensive 15-year Analysis of the Arizona Cancer Registry. AB - INTRODUCTION: The aim of this study was to investigate and analyze the incidence of early-onset colorectal cancer in Arizona, using the Arizona Cancer Registry. METHODS: We performed a retrospective analysis of patients with colorectal cancer reported in the Arizona Cancer Registry from 1995-2010. Outcome measure: incidence of CRC in patients younger than 50 years. RESULTS: 39,623 cases of colorectal cancer were reported to the Arizona Cancer Registry during a period of 15 years. Overall, there was a 17% decrease in the incidence of CRC. However, there was a 23% increase in incidence among patients in the age group 10-50. During the same time period, 15% and 41% increase in the incidence of colon and rectal cancer was observed, respectively. The most significant increase (102%) in overall CRC incidence was seen in the age group 10-29. The highest increase (110%) in incidence of colon cancer was observed in the same age group, while the most significant increase in incidence rates (225%) of rectal cancer was seen in the age group 30-34. CONCLUSION: Although there is an overall decrease in incidence of colorectal cancer in Arizona, alarming increase in incidence of early-onset CRC was observed; mirroring the national trends. PMID- 27559495 TI - Dermatology in India and Indian dermatology: A Medico-Historical perspective. PMID- 27559496 TI - Microneedling: Advances and widening horizons. AB - Microneedling is a very simple, safe, effective, and minimally invasive therapeutic technique. It was initially introduced for skin rejuvenation, however, now it is being used for a very wide range of indications including acne scar, acne, post-traumatic/burn scar, alopecia, skin rejuvenation, drug delivery, hyperhidrosis, stretch marks, and many more. Moreover, during the last 10 years, many new innovations have been made to the initial instrument, which was used for microneedling. This technique can be combined with other surgical techniques to provide better results. In particular, it is a very safe technique for dark skin types, where risk of postinflammatory pigmentation is very high with other techniques that damage the epidermis. In this review article, we are updating on the different instruments now available for this procedure, and its efficacy when performed alone or in combination with other techniques for various indications. PMID- 27559494 TI - Novel Therapeutic Strategies for the Management of Ventricular Arrhythmias Associated with the Brugada Syndrome. AB - INTRODUCTION: Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome characterized by prominent J waves appearing as distinct coved type ST segment elevation in the right precordial leads of the ECG. It is associated with a high risk for sudden cardiac death. AREAS COVERED: We discuss 1) ECG manifestations of BrS which can be unmasked or aggravated by sodium channel blockers, febrile states, vagotonic agents, as well as tricyclic and tetracyclic antidepressants; 2) Genetic basis of BrS; 3) Ionic and cellular mechanisms underlying BrS; 4) Therapy involving devices including an implantable cardioverter defibrillator (ICD); 5) Therapy involving radiofrequency ablation; and 6) Therapy involving pharmacological therapy which is aimed at producing an inward shift in the balance of the currents active during phase 1 of the right ventricular action potential either by boosting calcium channel current (isoproterenol, cilostazol and milrinone) or by inhibition of transient outward current Ito (quinidine, bepridil and the Chinese herb extract Wenxin Keli). EXPERT OPINION: This review provides an overview of the clinical and molecular aspects of BrS with a focus on approaches to therapy. Available data suggest that agents capable of inhibiting the transient outward current Ito can exert an ameliorative effect regardless of the underlying cause. PMID- 27559497 TI - Quality of life in patients with erythema nodosum leprosum in Kuala Lumpur, Malaysia. AB - BACKGROUND: There is a paucity of data on quality of life issues in patients with leprosy suffering from erythema nodosum leprosum (ENL). Thus, we aim to study the effect of ENL on quality of life. MATERIALS AND METHODS: This cross-sectional study was conducted in Hansen's Clinic, Hospital Kuala Lumpur between January 2010 and December 2013 among patients with multibacillary leprosy using the Dermatology Life Quality Index (DLQI). RESULTS: A total of 153 patients participated with 31.4% suffering from ENL. The mean age at presentation was 40.5 +/- 16.49 years. The mean DLQI was 7.1 +/- 3.72. Patients with ENL were younger (mean age 36.5 vs. 42.4, P = 0.026), had higher mean bacteriologic index (4.3 vs. 3.8, P = 0.004), had physical deformities (47.9% vs. 31.4%, P = 0.049), and had higher mean DLQI score (9.1 vs. 6.2, P < 0.001). All the DLQI domains were higher in patients suffering from ENL except the treatment domain. Symptoms and feeling was the domain with the largest effect followed by daily activities and leisure. Personal relationship had the lowest effect. CONCLUSION: Quality of life impairment in patients with leprosy in Malaysia is moderate, with larger effect among patients with ENL. The impairment in ENL is comparable to itchy skin conditions such as urticarial and is worse than chronic skin disease such as psoriasis. Thus, it is essential that management of leprosy incorporate quality of life issues. PMID- 27559498 TI - Misuse of topical corticosteroids on the face: A cross-sectional study among dermatology outpatients. AB - BACKGROUND: Topical corticosteroids (TC) are being misused widely on the face without a prescription from the dermatologist. AIM: To evaluate the misuse of TC containing preparations on the face and the adverse effects due to its application. MATERIALS AND METHODS: A questionnaire-based analysis was done among patients attending the dermatology outpatient department of a tertiary care hospital between March 2014 and March 2015. Patients with various facial dermatoses were asked about their current use of topical preparations and on further followup questioning, those who revealed the use of TCs (25g or more) continuously or intermittently for a minimum duration of four weeks were included in the study and observed for local adverse effects. RESULTS: A total of 410 patients were observed, 306 were females (74.6%) and 104 were males (25.3%). One hundred and seventy-eight patients (43.4%) used topical steroids alone, 124 (30.2%) used creams containing TC, hydroquinone, and tretinoin, 108 (26.3%) used creams containing a combination of TC, antibiotic, and/or antifungal. One hundred and seventy-six patients (42.9%) bought TC or TC containing creams over the counter on their own, without the prescription of a dermatologist, 35 (8.5%) were recommended TC by a beautician (beauty parlors), 82 (20%) by their friends, family members, or neighbors, 75 (18.2%) by a non-dermatologist practitioner, and 42 (10.2%) by a dermatologist. LIMITATIONS: The sample size was small. CONCLUSION: Dispensing of TCs must be regulated in India; they should only be issued against a doctor's prescription. PMID- 27559499 TI - Clinico-microbiological study of dermatophytosis in a tertiary-care hospital in North Karnataka. AB - CONTEXT: The dermatophytoses constitute a group of superficial fungal infections of keratinized tissues, namely, the epidermis, hair, and nails. The distribution and frequency of dermatophytosis and their etiologic agents vary according to the geographic region studied, the socio-economic level of the population, the time of study, the climatic variations, the presence of domestic animals, and age. AIMS: The present study was undertaken to assess the clinical profile of dermatophytic infections and to identify the causative fungal species in the various clinical presentations. SETTINGS AND DESIGN: This was a hospital-based observational study. MATERIALS AND METHODS: One hundred and fifty clinically suspected cases of dermatophytosis attending the outpatient department of a tertiary care hospital were included in the study. History was taken, general physical and cutaneous examination was done and details of skin lesions noted. Direct microscopy in 10% KOH (40% KOH for nail) and fungal culture on SDA with 0.05% chloramphenicol and 0.5% cycloheximide was done in every case. STATISTICAL ANALYSIS USED: Statistical analysis was done using SPSS 17.0 software. Chi-square test and contingency coefficient test were used as significant tests for analysis. RESULTS: Out of 150 patients studied, majority belonged to the age group of 21-30 years (22.7%). Male-to-female ratio was 1.63:1. Tinea corporis (24.7%) was the most common clinical type observed. The overall positivity by culture was 40% and by direct microscopy was 59.3%. Trichophyton mentagrophytes was the predominant species isolated (48.3%). CONCLUSIONS: The present study reveals the changing trend in the prevalence of dermatophyte species in this part of Karnataka. PMID- 27559500 TI - Cystic acantholytic dyskeratosis of the vulva: An unusual presentation of a follicular adnexal neoplasm. AB - Acantholytic dyskeratosis (AD) is a histologic pattern seen in Darier's disease or dyskeratosis follicularis, warty dyskeratoma, and transient AD. This pattern is characterized by suprabasilar clefting, acantholysis, and formation of corps ronds and grains. We present a case of AD that is unique based on its genital location and cystic architecture. A 53-year-old woman presented with an otherwise asymptomatic cyst on her left vulva of uncertain duration. On microscopic examination, there were fragments of cystic epithelium with areas of hypergranulosis, acantholysis, corps ronds, and corps grains formation. These features are felt by the authors to be a unique presentation of a follicular adnexal neoplasm. PMID- 27559501 TI - Dyskeratosis congenita presenting with dysphagia. AB - Dyskeratosiscongenita (DKC) is a genetically heterogeneous disease of defective telomere maintenance that may demonstrate different patterns of inheritance. It is characterized by thetriad of dystrophy of the nails, leukokeratosis of the oral mucosa, and extensive net-like pigmentation of the skin. We report a case ofDKC who presented with a chief complaint of dysphagia. PMID- 27559502 TI - Pachyonychia congenita with late onset (PC tarda). AB - Pachyonychia congenita is a rare type of ectodermal dysplasia further classified into 4 types. Cutaneous manifestations seen in most of the cases of Pachyonychia congenita include palmoplantar keratoderma, follicular hyperkeratosis, wedge shaped nails, oral leukokeratosis and woolly hair. A 25-year-old male presented to us with thickened nails and scanty scalp hair. On examination, we noticed hyperkeratotic plaques over both the soles, palmoplantar hyperhidrosis and yellowish discoloration, wedging with subungual hyperkeratosis of all the nails. Follicular hyperkeratotic papules and steatocystoma multiplex were also observed over the scalp and face. The patient had history of natal teeth and on dental examination, lower central incisors were absent. All cutaneous changes in our case had manifested first in the 2(nd) decade except for natal teeth. All the above features suggested the diagnosis of pachyonychia congenita with late onset (PC tarda), which is an infrequently reported rare variant. PMID- 27559503 TI - Cutaneous metastases from signet cell carcinoma of the gut: A report of two cases. AB - Cutaneous metastasis from visceral tumors is a rare entity with a reported incidence between 0.3% and 9.8%. These usually occur late in the course of the disease; the average time interval between the diagnosis of malignancy and presentation of cutaneous metastases has been reported to be 33 months. In rare instances (in about 0.8%-1.3% of patients), cutaneous metastases may be a pointer to an underlying undiagnosed malignancy. We report two patients presenting to us with soft, nodular, cutaneous lesions, which was the manifestation of metastatic signet cell carcinoma arising from the gut. We report these cases owing to their rarity. PMID- 27559504 TI - Fibroepithelioma of Pinkus in continuity with nodular basal cell carcinoma: A rare presentation. AB - Fibroepithelioma of Pinkus and nodular basal cell carcinoma (BCC) are different morphological variants of BCC. It is very rare to see both the variants together in a single lesion. Here we report a case of a 56-year-old female who presented with a nodule on the trunk, which on biopsy showed features of both nodular BCC and fibroepithelioma of Pinkus. PMID- 27559505 TI - Huriez syndrome with superadded dermatophyte infection. AB - Palmoplantarkeratodermas (PPKs) are a heterogeneous group of hereditary and acquired disorders with underlying gene defects, and characterized by hyperkeratosis of palms and soles with or without other ectodermal and systemic abnormalities. Huriez syndrome is a rare autosomal dominant transgradient type of PPK with high frequency of squamous cell carcinoma in the affected skin. We hereby describe a case of a very rare autosomal dominant PPK in a 40-year-old male patient presenting since birth with PPK extending onto the dorsal aspects of hands and feet with peeling of the skin. The complaints were associated with sclerodactyly, hyperhidrosis, and nail abnormalities. Also superadded dermatophyte infection was observed involving abdomen. No history of loss of any digit. No mucosal, dental, or any systemic involvement was present. No sign of malignancy was noted. Baseline investigations, including ultrasonography of abdomen were normal. Histological findings were nonspecific with only orthohyperkeratosis and acanthosis. Diagnosis was mainly done on clinical grounds. The patient is better with oral retinoids and topical emollients and keratolytics along with antifungal treatment for dermatophyte infection. He is under follow up. PMID- 27559506 TI - Clinical and dermatoscopic features of porokeratosis palmaris et plantaris. AB - A dermatoscope is an important tool in a dermatologist's armamentarium as it can eliminate the need for a biopsy in a wide array of conditions. Porokeratosis was described by Mibelli and Respighi in 1893, as a disorder of keratinization which on the basis of distribution patterns was described as five clinical variants that portrayed a coronoid lamella on histopathology. We describe a case of asymptomatic, long-standing palmar and plantar pits, which on dermatoscopy showed features suggestive of porokeratosis, which was later reconfirmed by histopathologic sections. This report depicts diagnostic features of porokeratosis and obviates the need for invasive procedures for its diagnosis. PMID- 27559507 TI - Macrodystrophia lipomatosa: Review of clinico-radio-histopathological features. AB - We report clinical, radiological, and pathological features of three cases of macrodystrophia lipomatosa, which is characterized by progressive proliferation of all mesenchymal elements, with a disproportionate increase in fibroadipose tissue. The peculiarity in our report is the involvement of contralateral hand and feet in our 1(st) case in contrast to usual presentations of this rare condition, which is often unilateral. In our 2(nd) case, the lateral aspect of foot was involved as against the usual finding of involvement of medial aspect in lower limbs, also another surprising finding in this case is increase in the size of lesion after puberty. Coming to our 3(rd) case, enlargement of almost whole of an upper extremity with profound involvement of middle, ring and little finger along with total sparing of the thumb is in itself an extremely rare occurrence as in upper limb, mainly the lateral aspect of hand and related digits bear the burnt and more over involvement of whole limb is itself an unique phenomenon. PMID- 27559508 TI - Cutaneous tuberculosis with a difference: Documenting transfollicular elimination of granulomas. AB - A patient presented with a an asymptomatic brown to erythematous, scaly indurated solitary plaque on his elbow. The lesion was diagnosed as lupus vulgaris on the basis of clinical features and biopsy findings. The histopathology further revealed a granuloma within the follicular infundibulum, which was possibly being expelled out. The phenomenon of transepidermal elimination has been described previously in many conditions, including cutaneous tuberculosis; however, transfollicular elimination of the granuloma has not been reported. We report this unusual phenomenon as a possible mode of elimination of the granuloma. PMID- 27559509 TI - Erythema elevatum diutinum in association with IgA monoclonal gammopathy: A rare case report. AB - Erythema elevatum diutinum (EED) is a rare form of vasculitis characterized clinically by red-violet brown papules, plaques, and nodules mainly involving the extensor surfaces; histologically by leukocytoclastic vasculitis in early lesions, and fibrosis and cholesterolosis in late lesions. EED has been associated with many systemic disorders including infections, autoimmune disorders, and both benign and malignant hematological disorders. As it is a rare form of vasculitis and only 250 cases reported till date, we report a case of EED in association with IgA monoclonal gammopathy with partial response to dapsone treatment. PMID- 27559510 TI - Seronegative necrolytic acral erythema: A report of two cases and literature review. AB - Necrolytic acral erythema (NAE) is a newly described entity, seen in patients infected with hepatitis C virus. It is characterized by its distinguishing acral distribution, psoriasiform skin eruption and histological features. Its etiopathogenesis is not fully understood though hypo amino academia, hyperglucagonemia and zinc deficiency are considered as probable causes. In 1996, El Darouti and Abu el Ela first described this entity in seven Egyptian patients with hepatitis C virus (HCV). Since then, several small studies and cases have been reported around the world. Nevertheless, it may occur independently without HCV association as a few cases have been reported recently. We report two seronegative cases of NAE, which responded dramatically with oral zinc therapy. This suggests that NAE could be an isolated clinical subset. PMID- 27559511 TI - Cellular dermatofibroma: A hyperkeratotic indurated plaque on the thigh. PMID- 27559513 TI - Idiopathic hemihypertrophy with multiple fibroadenoma. PMID- 27559512 TI - Vitamin E in dermatology. AB - Vitamin E is an important fat-soluble antioxidant and has been in use for more than 50 years in dermatology. It is an important ingredient in many cosmetic products. It protects the skin from various deleterious effects due to solar radiation by acting as a free-radical scavenger. Experimental studies suggest that vitamin E has antitumorigenic and photoprotective properties. There is a paucity of controlled clinical studies providing a rationale for well-defined dosages and clinical indications of vitamin E usage in dermatological practice. The aim of this article is to review the cosmetic as well as clinical implications of vitamin E in dermatology. PMID- 27559514 TI - Lupus vulgaris in classical sporotrichoid pattern. PMID- 27559515 TI - Necrotizing fasciitis associated with systemic lupus erythematosus in a child. PMID- 27559516 TI - A rare case of multiple keratoacanthomas treated with oral acitretin and intralesional methotrexate. PMID- 27559517 TI - Eyelid excoriation and erythema with nepafenac eye drop. PMID- 27559518 TI - Reactive eccrine syringofibroadenoma in hyperkeratotic eczema. PMID- 27559519 TI - Aquagenic syringeal acrokeratoderma. PMID- 27559520 TI - Giant bilateral Becker's nevus appearing as gladiator arm armor. PMID- 27559521 TI - Half and half blisters in pemphigus vulgaris: A diagnostic quandary. PMID- 27559522 TI - Pyoderma gangrenosum associated with mantle cell lymphoma. PMID- 27559523 TI - Comparative assessment of the efficacy of topical ketoconazole and topical luliconazole in cases of pityriasis versicolor at a tertiary care hospital in eastern India: A prospective, open, randomized controlled trial. PMID- 27559524 TI - Cerebrotendinous xanthomatosis. PMID- 27559525 TI - Acral lentiginous melanoma with multiple brain metastases in an Indian male. PMID- 27559526 TI - Annular atrophic plaque over the arm. PMID- 27559527 TI - A study of postherpetic pruritus. PMID- 27559528 TI - Extrafacial melasma over forearms. PMID- 27559529 TI - Trigeminal trophic syndrome. PMID- 27559530 TI - Sk India Quiz 26: Hypopigmented papules in a human immunodeficiency virus positive patient. PMID- 27559531 TI - SkIndia Quiz 27: Rhinophyma and numerous facial papule and nodules in a 39-year old woman. PMID- 27559532 TI - Mycetoma. PMID- 27559533 TI - Black discoloration of palms. PMID- 27559535 TI - Early Esophageal Cancer Specific Survival Is Unaffected by Anatomical Location of Tumor: A Population-Based Study. AB - Background. Approximately one-fifth of all esophageal cancer cases are defined as early esophageal cancer (EEC). Although endoscopic therapy (ET) has been shown to be equally effective as esophagectomy (EST) in patients with EEC, there is little information comparing the survival outcomes of the two therapies based on anatomical location. Methods. A population-based study was conducted and the data was obtained from Surveillance, Epidemiology, and End Results program. Patients with EEC (i.e., stages Tis and T1a) and treated with either ET or EST were analyzed to compare EEC-related survival for three different locations of tumor. Results. The overall EEC-specific 1-year and 5-year mean (+/-SE) survival rates were 11.66 +/- 0.05 and 52.80 +/- 0.58 months, respectively. Tumors located in lower third had better 5-year survival compared to those located in middle third (83.50% versus 73.10%, p < 0.01). However, when adjusted for age, race, gender, marital status, grade, stage of tumor, histological type, and treatment modality, there was no significant difference. Conclusion. The EEC-specific 1-year or 5 year adjusted survival did not differ by anatomic location of the tumor. Therefore, ET might serve as a minimally invasive yet effective alternative to EST to treat EEC. PMID- 27559534 TI - A Journey of Cytolethal Distending Toxins through Cell Membranes. AB - The multifunctional role of lipids as structural components of membranes, signaling molecules, and metabolic substrates makes them an ideal partner for pathogens to hijack host cell processes for their own survival. The properties and composition of unique membrane micro-domains such as membrane rafts make these regions a natural target for pathogens as it affords them an opportunity to hijack cell signaling and intracellular trafficking pathways. Cytolethal distending toxins (Cdts), members of the AB2 family of toxins are comprised of three subunits, the active, CdtB unit, and the binding, CdtA-CdtC unit. Cdts are cyclomodulins leading to cell cycle arrest and apoptosis in a wide variety of cell types. Cdts from several species share a requirement for membrane rafts, and often cholesterol specifically for cell binding and CdtB mediated cytotoxicity. In this review we focus on how host-cell membrane bilayer organization contributes to the cell surface association, internalization, and action of bacteria derived cytolethal distending toxins (Cdts), with an emphasis on Aggregatibacter actinomycetemcomitans Cdt. PMID- 27559536 TI - Functional Capacity, Respiratory Muscle Strength, and Oxygen Consumption Predict Mortality in Patients with Cirrhosis. AB - Introduction. Liver diseases influence musculoskeletal functions and may negatively affect the exercise capacity of patients with cirrhosis. Aim. To test the relationship between the six-minute walk test (6MWT), maximal inspiratory pressure (MIP), and exercise capacity (VO2peak) measures and the survival rate of patients with cirrhosis. Methods. This prospective cohort study consisted of 86 patients diagnosed with cirrhosis with the following aetiology: hepatitis C virus (HCV), hepatitis B virus (HBV), and/or alcoholic cirrhosis (AC). All patients were followed up for three years and submitted to the 6MWT, pressure measurements with a compound gauge, and an exercise test (VO2peak). Results. The survival analysis showed that the individuals who covered a distance shorter than 410 m during the 6MWT had a survival rate of 55% compared with a rate of 97% for the individuals who walked more than 410 m (p = 0.0001). Individuals with MIPs below 70 cmH2O had a survival rate of 62% compared with a rate of 93% for those with MIPs above -70 cmH2O (p = 0.0001). The patients with values below 17 mL/kg had a survival rate of 55% compared with a rate of 94% for those with values above 17 mL/kg (p = 0.0001). Conclusion. The 6MWT distance, MIP, and oxygen consumption are predictors of mortality in patients with cirrhosis. PMID- 27559537 TI - Growth in Children with Autosomal Recessive Polycystic Kidney Disease in the CKiD Cohort Study. AB - BACKGROUND: Previous studies have suggested that some children with autosomal recessive polycystic kidney disease (ARPKD) have growth impairment out of proportion to their degree of chronic kidney disease (CKD). The objective of this study was to systematically compare growth parameters in children with ARPKD to those with other congenital causes of CKD in the chronic kidney disease in Children (CKiD) prospective cohort study. METHODS: Height SD scores (z-scores), proportion of children with severe short stature (z-score < -1.88), rates of growth hormone use, and annual change in height z-score were analyzed in children with ARPKD (n = 22) compared with two matched control groups: children with aplastic/hypoplastic/dysplastic kidneys (n = 44) and obstructive uropathy (OU) (n = 44). Differences in baseline characteristics were tested by Wilcoxon rank-sum test or Fisher's exact test. Matched differences in annual change in height z score were tested by Wilcoxon signed-rank test. RESULTS: Median height z-score in children with ARPKD was -1.1 [interquartile range -1.5, -0.2]; 14% of the ARPKD group had height z-score < -1.88, and 18% were using growth hormone. There were no significant differences in median height z-score, proportion with height z score < -1.88, growth hormone use, or annual change in height z-score between the ARPKD and control groups. CONCLUSION: Children with ARPKD and mild-to-moderate CKD in the CKiD cohort have a high prevalence of growth abnormalities, but these are similar to children with other congenital causes of CKD. This study does not support a disease-specific effect of ARPKD on growth, at least in the subset of children with mild-to-moderate CKD. PMID- 27559538 TI - Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic-Ischemic Brain Injury. AB - Seizures are common following hypoxic-ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome c-oxidase (Delta[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic-ischemic encephalopathy in a newborn infant. A rapid increase in Delta[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Delta[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Delta[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism. PMID- 27559539 TI - Where Are We Now with the Role of Steroids in the Management of Bronchopulmonary Dysplasia in Extremely Premature Babies? PMID- 27559540 TI - A Call to Action: Building a Translational Inclusion Team Science in Physical Activity, Nutrition, and Obesity Management for Children with Disabilities. AB - The growing evidence base of childhood obesity prevention and treatment programs do not adequately consider how to adapt these programs for children with disabilities. We propose a Call to Action for health researchers who conduct studies focused on the general population (i.e., without a disability) to work closely with disability researchers to adapt their programs (e.g., obesity management, increased physical activity, and caregiver training in diet and nutrition) to be relevant to both groups. We refer to this approach as inclusion team science. The hope for this Call to Action is that there will be greater synergy between researchers who have high levels of expertise in a specialty area of health (but little or no knowledge of how to adapt their program for children with disabilities) to work more closely with researchers who have a high level of expertise in adapting evidence-based health promotion recommendations and strategies for children with disabilities. Together, these two areas of expertise will lead to inclusive physical activity and nutrition programs for all children. PMID- 27559541 TI - Methods for Detecting Microbial Methane Production and Consumption by Gas Chromatography. AB - Methane is an energy-dense fuel but is also a greenhouse gas 25 times more detrimental to the environment than CO2. Methane can be produced abiotically by serpentinization, chemically by Sabatier or Fisher-Tropsh chemistry, or biotically by microbes (Berndt et al., 1996; Horita and Berndt, 1999; Dry, 2002; Wolfe, 1982; Thauer, 1998; Metcalf et al., 2002). Methanogens are anaerobic archaea that grow by producing methane gas as a metabolic byproduct (Wolfe, 1982; Thauer, 1998). Our lab has developed and optimized three different gas chromatograph-utilizing assays to characterize methanogen metabolism (Catlett et al., 2015). Here we describe the end point and kinetic assays that can be used to measure methane production by methanogens or methane consumption by methanotrophic microbes. The protocols can be used for measuring methane production or consumption by microbial pure cultures or by enrichment cultures. PMID- 27559542 TI - Lymphopenia in treatment-naive relapsing multiple sclerosis. PMID- 27559546 TI - Elizabeth Anderson: Cancer Risk Assessment Pioneer. PMID- 27559543 TI - Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex. AB - Nicotinic acetylcholine receptors (nAChRs) support the initiation and maintenance of smoking, but the long-term changes occurring in the protein complex as a result of smoking and the nicotine in tobacco are not known. Human studies and animal models have also demonstrated that increasing cholinergic tone increases behaviors related to depression, suggesting that the nAChR-associated proteome could be altered in individuals with mood disorders. We therefore immunopurified nAChRs and associated proteins for quantitative proteomic assessment of changes in protein-protein interactions of high-affinity nAChRs containing the beta2 subunit (beta2*-nAChRs) from either cortex of mice treated with saline or nicotine, or postmortem human temporal cortex tissue from tobacco-exposed and nonexposed individuals, with a further comparison of diagnosed mood disorder to control subjects. We observed significant effects of nicotine exposure on the beta2*-nAChR-associated proteome in human and mouse cortex, particularly in the abundance of the nAChR subunits themselves, as well as putative interacting proteins that make up core components of neuronal excitability (Na/K ATPase subunits), presynaptic neurotransmitter release (syntaxins, SNAP25, synaptotagmin), and a member of a known nAChR protein chaperone family (14-3 3zeta). These findings identify candidate-signaling proteins that could mediate changes in cholinergic signaling via nicotine or tobacco use. Further analysis of identified proteins will determine whether these interactions are essential for primary function of nAChRs at presynaptic terminals. The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets. PMID- 27559545 TI - Concentration dynamics of coarse and fine particulate matter at and around signalised traffic intersections. AB - The understanding of rapidly evolving concentrations of particulate matter (PMC) at signalised traffic intersections (TIs) is limited, but it is important for accurate exposure assessment. We performed "mobile" and "fixed-site" monitoring of size-resolved PMCs in the 0.25-34 MUm range at TIs. On-road mobile measurements were made inside a car under five different ventilation settings on a 6 km long round route, passing through 10 different TIs. Fixed-site measurements were conducted at two types (3- and 4-way) of TIs. The aims were to assess the effects of different ventilation settings on in-vehicle PMCs and their comparison during delay conditions at the TIs with those experienced by pedestrians while crossing these TIs. We also estimated the zone of influence (ZoI) for PM10, PM2.5 and PM1 under different driving conditions and fitted the probability distribution functions to fixed-site data to understand the concentration and exposure dynamics of coarse and fine particles around the studied (3- and 4-way) TIs. The fine particles (PM2.5) showed a strong positive exponential correlation with the air exchange rates under different ventilation settings compared with coarse particles (PM2.5-10) showing an opposite trend. This suggested that the ventilation system of the car was relatively more efficient in removing coarse particles from the incoming outside air. On-road median PM10, PM2.5 and PM1 during delays at the TIs were ~40%, 16% and 17% higher, respectively, compared with free-flow conditions on the rest of the route. About 7% of the average commuting time spent during delay conditions over all the runs at the TIs corresponded to 10, 7 and 8% of the total respiratory deposition dose (RDD) for PM10, PM2.5 and PM1, respectively. The maximum length of the ZoI for PM2.5 and PM1 was highest at the 4-way TI and the maximum length of the ZoI for PM10 was highest at the 3-way TI. The on-road average RDD rate of PM10 inside the cabin when windows were fully open was up to ~7-times that for pedestrians at the TIs. PMID- 27559544 TI - Genetic Polymorphisms of TLR4 and MICA are Associated with Severity of Trachoma Disease in Tanzania. AB - AIM: To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. METHODS: The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan(r), respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. RESULTS: The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. CONCLUSION: TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic. PMID- 27559547 TI - Editor's Note. PMID- 27559548 TI - DETERMINATION OF CRITICAL POWER AND ANAEROBIC WORK CAPACITY: IS ONE TEST BETTER THAN TWO?In Response. PMID- 27559549 TI - Social work. PMID- 27559606 TI - Surface Engineering of Cellulose Nanofiber by Adsorption of Diblock Copolymer Dispersant for Green Nanocomposite Materials. AB - An effective approach for the dispersion of hydrophilic cellulose nanofiber (CNF) in hydrophobic high-density polyethylene (HDPE) is presented using adsorption of a diblock copolymer dispersant. The dispersant consists of both resin compatible poly(lauryl methacrylate) (PLMA) and cellulose interactive poly(2-hydroxyethyl methacrylate) blocks. The PLMA-adsorbed CNFs are characterized by FT-IR and contact angle measurement, revealing successful hydrophobization. X-ray CT imaging shows there are apparently less CNF aggregates in the nanocomposites if adding amount of the dispersant was enough. The good dispersion results in a high mechanical reinforcement, corresponding to 140% higher Young's modulus and 84% higher tensile strength than the neat HDPE. This approach is broadly applicable and allows for easy manufacturing process for strong and lightweight CNF reinforced nanocomposite materials. PMID- 27559607 TI - Protein Interaction Network of Human Protein Kinase D2 Revealed by Chemical Cross Linking/Mass Spectrometry. AB - We investigated the interaction network of human PKD2 in the cytosol and in Golgi enriched subcellular protein fractions by an affinity enrichment strategy combined with chemical cross-linking/mass spectrometry (MS). Analysis of the subproteomes revealed the presence of distinct proteins in the cytosolic and Golgi fractions. The covalent fixation of transient or weak interactors by chemical cross-linking allowed capturing interaction partners that might otherwise disappear during conventional pull-down experiments. In total, 31 interaction partners were identified for PKD2, including glycogen synthase kinase 3 beta (GSK3B), 14-3-3 protein gamma (YWHAG), and the alpha isoform of 55 kDa regulatory subunit B of protein phosphatase 2A (PPP2R2A). Remarkably, the entire seven-subunit Arp2/3 complex (ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ACTR3, ACTR2) as well as ARPC1A and ARPC5L, which are putative substitutes of ARPC1B and ARPC5, were identified. We provide evidence of a direct protein-protein interaction between PKD2 and Arp2/3. Our findings will pave the way for further structural and functional studies of PKD2 complexes, especially the PKD2/Arp2/3 interaction, to elucidate the role of PKD2 for transport processes at the trans-Golgi network. Data are available via ProteomeXchange with identifiers PXD003909 (enrichment from cytosolic fractions), PXD003913 (enrichment from Golgi fractions), and PXD003917 (subcellular fractionation). PMID- 27559608 TI - Tracking Pseudocapacitive Contribution to Superior Energy Storage of MnS Nanoparticles Grown on Carbon Textile. AB - Transition metal chalcogenides have emerged as a new class of electrode materials for energy storage devices with superior electrochemical performance. We have directly synthesized manganese sulfide nanoparticles on carbon textile substrate and used them as electrodes to fabricate flexible all-solid-state supercapacitors. By voltammetry analysis, we have studied the electrochemical properties of MnS-CT composites, which reveal that the Faradaic diffusion controlled process dominates at low scan rates (82.85% at 5 mV s(-1)) and even at high scan rates (39% at 20 mV s(-1)). The MnS-CT electrode shows high capacitance of 710.6 F g(-1) in LiCl aqueous electrolyte, and the surface redox reactions on MnS nanoparticles are found to be responsible for the high pseudocapacity, which is further analyzed by XRD and HRTEM. Furthermore, MnS-CT supercapacitor exhibits excellent pseudocapacitive performance (465 Fg(-1) at 5 mV s(-1)), excellent stability, light weight (0.83 g as a whole device), and high flexibility. The device has also achieved high energy density and high power density (52 Wh kg(-1) at 308 W kg(-1) and 1233 W kg(-1) with 28 Wh kg(-1), respectively). In practice, three charged supercapacitors in series can power four red light-emitting diodes (LEDs) (2.0 V, 15 mA) for 2 min. All of the evidence shows that MnS nanoparticles combined with carbon textile is a promising electrode material for pseudocapacitors. PMID- 27559609 TI - Controlling the morphology and material characteristics of electrospray generated calcium alginate microhydrogels. AB - Electrospraying nano- and micro-particle fabrication is a one-step, non-invasive process, which has application in encapsulating of thermosensitive functional, bioactive materials and cells and making microhydrogels. This study investigates the effect of various electrospraying process parameters on the characteristics of calcium alginate microhydrogel particles. The alginate solution concentration, CaCl2 coagulation bath concentration, voltage, nozzle diameter, distance between nozzle and collecting bath (D), alginate delivery pressure (~H) were examined. The best droplet formation rate, in non-disperse dripping mode, was obtained at 8 kV using a 500 MUm inner diameter nozzle tip, D = 8 cm, H = 20 cm. Morphology, swelling behaviour and texture analysis of the particles which were followed by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) confirmed that 1.5-2% (w/v) CaCl2 was the desirable concentration for hydrogels formation. Particle size range between 267 and 1500 MUm could be obtained by the drip feed mode compared with 2.3-6 MUm by the pressure-assisted electrospray through a coaxial head. PMID- 27559610 TI - Dynamic Memory Cells Using MoS2 Field-Effect Transistors Demonstrating Femtoampere Leakage Currents. AB - Two-dimensional semiconductors such as transition-metal dichalcogenides (TMDs) are of tremendous interest for scaled logic and memory applications. One of the most promising TMDs for scaled transistors is molybdenum disulfide (MoS2), and several recent reports have shown excellent performance and scalability for MoS2 MOSFETs. An often overlooked feature of MoS2 is that its wide band gap (1.8 eV in monolayer) and high effective masses should lead to extremely low off-state leakage currents. These features could be extremely important for dynamic memory applications where the refresh rate is the primary factor affecting the power consumption. Theoretical predictions suggest that leakage currents in the 10(-18) to 10(-15) A/MUm range could be possible, even in scaled transistor geometries. Here, we demonstrate the operation of one- and two-transistor dynamic memory circuits using MoS2 MOSFETs. We characterize the retention times in these circuits and show that the two-transistor memory cell reveals MoS2 MOSFETs leakage currents as low as 1.7 * 10(-15) A/MUm, a value that is below the noise floor of conventional DC measurements. These results have important implications for the future use of MoS2 MOSFETs in low-power circuit applications. PMID- 27559611 TI - Functional diversity of excitatory commissural interneurons in adult zebrafish. AB - Flexibility in the bilateral coordination of muscle contraction underpins variable locomotor movements or gaits. While the locomotor rhythm is generated by ipsilateral excitatory interneurons, less is known about the commissural excitatory interneurons. Here we examined how the activity of the V0v interneurons - an important commissural neuronal class - varies with the locomotor speed in adult zebrafish. Although V0v interneurons are molecularly homogenous, their activity pattern during locomotion is not uniform. They consist of two distinct types dependent on whether they display rhythmicity or not during locomotion. The rhythmic V0v interneurons were further subdivided into three sub classes engaged sequentially, first at slow then intermediate and finally fast locomotor speeds. Their order of recruitment is defined by scaling their synaptic current with their input resistance. Thus we uncover, in an adult vertebrate, a novel organizational principle for a key class of commissural interneurons and their recruitment pattern as a function of locomotor speed. PMID- 27559613 TI - Self-Supported Cedarlike Semimetallic Cu3P Nanoarrays as a 3D High-Performance Janus Electrode for Both Oxygen and Hydrogen Evolution under Basic Conditions. AB - There has been strong and growing interest in the development of cost-effective and highly active oxygen evolution reaction (OER) electrocatalysts for alternative fuels utilization and conversion devices. We report herein that semimetallic Cu3P nanoarrays directly grown on 3D copper foam (CF) substrate can function as effective electrocatalysts for water oxidation. Specifically, the surface oxidation-activated Cu3P only required a relatively low overpotential of 412 mV to achieve a current density of 50 mA cm(-2) and displayed a small Tafel slope of 63 mV dec(-1) in 0.1 M KOH solution, on account of the collaborative effect of large roughness factor (RF) and semimetallic character. Following that, investigations into the mechanism revealed the formation of a unique active phase during the water oxidation process in which conductive Cu3P was the core covered with a thin copper oxide/hydroxide layer. Moreover, this Cu3P 3D electrode was also applied to the hydrogen evolution reaction (HER) and showed good catalytic performance and stability under the same basic conditions. PMID- 27559612 TI - Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. AB - Exosomes are small vesicles that are secreted from metazoan cells and may convey selected membrane proteins and small RNAs to target cells for the control of cell migration, development and metastasis. To study the mechanisms of RNA packaging into exosomes, we devised a purification scheme based on the membrane marker CD63 to isolate a single exosome species secreted from HEK293T cells. Using immunoisolated CD63-containing exosomes we identified a set of miRNAs that are highly enriched with respect to their cellular levels. To explore the biochemical requirements for exosome biogenesis and RNA packaging, we devised a cell-free reaction that recapitulates the species-selective enclosure of miR-223 in isolated membranes supplemented with cytosol. We found that the RNA-binding protein Y-box protein I (YBX1) binds to and is required for the sorting of miR 223 in the cell-free reaction. Furthermore, YBX1 serves an important role in the secretion of miRNAs in exosomes by HEK293T cells. PMID- 27559614 TI - Immunomodulatory effects of turmeric: Proliferation of spleen cells in mice. AB - Experiments were conducted to examine the effects of turmeric on spleen cell proliferation. Cell suspensions of spleen cells from young and aged mice were treated with or without conconavalin A (Con-A) as a proliferation stimulant, and with and without turmeric (20 mg/mL) in different concentrations. Spleen cells from young mice that received turmeric showed significant increase in spleen cell proliferation (P < 0.05), while spleen cells from aged mice that received turmeric showed no significant increase in T lymphocytes. The data indicates that turmeric increases the ability of spleen cells in young mice to proliferate, in vitro. PMID- 27559615 TI - Synthesis and Biological Evaluation of N-((1-(4-(Sulfonyl)piperazin-1 yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1. AB - We previously disclosed the discovery of rationally designed N-((1-(4 (propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics. Representative analogue (+)-67 exhibited robust in vivo activity in the cerebral spinal fluid glycine biomarker model in both rodents and nonhuman primates. Furthermore, rodent microdialysis experiments also demonstrated that oral administration of (+)-67 significantly elevated extracellular glycine levels within the medial prefrontal cortex (mPFC). PMID- 27559616 TI - The effects of genuine eye contact on visuospatial and selective attention. AB - We investigated performance in a visuospatial discrimination task and selective attention task (Stroop task) while a live person's direct or averted gaze was presented as a task-irrelevant contextual stimulus. Based on previous research, we expected that response times to peripherally presented targets (Experiment 1) and to the Stroop stimuli (Experiment 2) would be longer in the context of direct versus averted gaze. Contrary to our expectations, the direct gaze context resulted in faster discrimination of visual targets and faster performance in the Stroop task compared with the averted gaze context. We propose that the observed results are explained by enhanced arousal elicited by genuine eye contact. (PsycINFO Database Record PMID- 27559617 TI - Becoming stranger: When future selves join the out-group. AB - One of the most powerful rules of interpersonal behavior is that people are kinder to members of their in-groups than to members of their out-groups. Are people also kinder to their future selves when they expect them to remain members of their current in-groups rather than become members of their current out groups? In 2 studies, participants in an emotionally charged debate expected either to remain on the same team or to join the opposing team when they returned the following week. Those who expected to join the opposing team were less willing to sacrifice for their future selves, leaving more of an unpleasant task for their future selves to finish and treating their future selves as unkindly as they treated a stranger. These results suggest that the rules that govern interpersonal behavior may also govern intertemporal behavior, and suggest new strategies to encourage prudent decisions. (PsycINFO Database Record PMID- 27559618 TI - Quality indicators for thyroid cancer surgery: current perspective. AB - INTRODUCTION: While the disease specific mortality of differentiated thyroid cancer has remained low with current treatments, its incidence has been steadily rising over the past several decades, and cancer related recurrence and morbidity have remained a significant problem. Quality indicators currently employed are relevant to the surgical intervention, but do not necessarily reflect oncological outcomes. Therefore, thyroid cancer specific surgical quality indicators, that offer insight into risk of cancer related morbidity and mortality are needed. AREAS COVERED: This review aims to discuss the role of measuring quality in thyroid surgical oncology and carry out a comprehensive review of potential quality indicators for thyroid cancer operations. The three quality indicators reviewed here are the postoperative radioactive iodine update by remnant thyroid tissue, the proportion of resected lymph nodes with evidence of metastases, and the post-operative serum thyroglobulin level. Expert commentary: Together, these quality indicators may be utilized to guide improvement of the quality of surgical care for this unique patient population. A critical future step in establishing the role of quality indicators for thyroid cancer surgery is the determination of cutoff values of each indicator in an evidence-based manner. PMID- 27559619 TI - Base-rate data and norms for the Rey Auditory Verbal Learning Embedded Performance Validity Indicator. AB - The present study examines the Rey Auditory Verbal Learning Test (RAVLT) Embedded Performance Validity Indicator (EPVI) for detecting performance validity. This retrospective study analyzes the performance of four groups of 879 participants comprised of 464 clinically referred patients with suspected dementia, 91 forensic patients identified as not exhibiting adequate effort on other measures of response bias, 25 patients with well documented TBI, and a random sample of 198 adults collected in the Gulf State of Oman. The EPVI was also put to the test using normative data collected from the literature. Using sensitivity and specificity analyses, the results indicate moderate to high sensitivity yet low specificity. In conclusion, the study shows that the EPVI is a reasonably good indicator for inadequate effort on the RAVLT but those who fail this measure might not necessarily be exhibiting adequate effort. The limitations and benefits of utilizing the EPVI in clinical practice are discussed. PMID- 27559620 TI - Disabled-2; an autophagic and apoptotic switch. PMID- 27559621 TI - Conjunctival cicatrizing disease presenting with lacrimal obstruction. AB - Patients with conjunctival cicatrizing disease may develop lacrimal obstruction. Little is published on lacrimal obstruction as the presenting feature of otherwise asymptomatic cicatrizing conjunctival disease. The records of all patients presenting between 1994 and 2015 with lacrimal obstruction found to have cicatrizing conjunctival disease were reviewed. Demographic details, clinical findings, disease progression and treatment were analyzed. Thirty-five patients (25 female), aged 43-91 years (median 74, mean 71.3 years) had epiphora and a mild conjunctival cicatrizing process. Nine patients had onset of epiphora after cataract surgery. All except one patient had obstruction of the proximal lacrimal system (punctum and/or canaliculus). In 14 cases, the obstruction was unilateral (both puncta or canaliculi), with one progressing to bilateral obstruction after 11 years. In 19, all 4 puncta or canaliculi were obstructed. Two patients had unilateral nasolacrimal duct obstruction; one developed contralateral canalicular obstruction 2 years later. Conjunctival biopsies were obtained in 19 of 35 cases (54%), and OCP immunohistochemistry was positive in 7/19 (37%). All other biopsies showed chronic inflammation. Two patients had lichen planus. In follow up (range 0.1-11 years, mean 3.2 years), 2 patients' conjunctival disease progressed mildly, and 3 progressed moderately, with 2 of these 5 having positive OCP immunohistochemistry, and 1 having lichen planus. Patients with conjunctival cicatrization may present with lacrimal obstruction, usually punctal or canalicular. Conjunctival disease is usually mild and non-progressive, but patients should be monitored for disease progression. PMID- 27559622 TI - Insights into the definition of terms in European medical device regulation. AB - INTRODUCTION: Medical devices comprise apparatus/instruments, software, and materials with therapeutic activities obtained by principal mechanisms of action different from pharmacological, immunological and metabolic, which are proper of medicinal products. In this context the key for the distinction between medicinal products and devices lies in the correct interpretation of these terms, which, although defined in a guideline, are still not univocally interpreted. Areas covered: This article discusses the definitions of pharmacological and non pharmacological mechanisms of action, such as the chemical and physical means. The aim is to give insights on the correct definition these terms in order to contribute to build the desired synergy between scientific and regulatory fields and promote a correct interpretation of the European regulatory framework as well as sustainable health and innovation. Expert commentary: We propose a series of definitions and a method to interpret those definitions within possible decision tree paradigm. Specifically, we propose to define the difference between the terms 'action' of a medical device compared to the 'mechanism of action' of such device. In any decisional procedure the correct interpretation of these and other correlated terms is needed to correctly assess whether a substance is a medicinal product or a medical device. PMID- 27559623 TI - The Impact of Hospice Services in the Care of Patients with Advanced Stage Nonsmall Cell Lung Cancer. AB - INTRODUCTION: Prior research has shown that advanced stage nonsmall cell lung cancer (NSCLC) patients enrolled in hospice care receive less aggressive treatment at the end of life (EOL) without compromising survival. Our purpose was to profile the continuum of care of these patients, exploring the connection between hospice enrollment and quality indicators for excellence in EOL cancer care. METHODS: One hundred ninety-seven deceased stage IV NSCLC patients diagnosed between 2008 and 2010 at two separate tertiary care centers within the same county were identified. A retrospective review was conducted, collecting data from electronic medical records regarding antitumor treatment, postdiagnosis hospital visits and admissions, hospice referrals and enrollments, and circumstances surrounding the patient's death. Patients were grouped by their status of hospice enrollment, and the remainder of the measures compared accordingly. RESULTS: There was no significant difference found in total number of postdiagnosis hospital admissions between the patients who were enrolled in hospice and those who were not. However, the group who received hospice services had a significantly lower number of hospitalizations (p < 0.001), emergency department visits (p < 0.01), and intensive care unit admissions in the last 30 days of life (p < 0.001). The number of lines of chemotherapy received did not differ significantly between the groups. Median survival, measured by the length of time between diagnosis and death, was significantly longer for hospice patients (p = 0.02). CONCLUSIONS: This study demonstrates that, among patients with metastatic NSCLC, hospice enrollment was associated with optimized EOL oncological care and a significantly longer median survival. PMID- 27559624 TI - Subtle perceptions of male sexual orientation influence occupational opportunities. AB - Theories linking the literatures on stereotyping and human resource management have proposed that individuals may enjoy greater success obtaining jobs congruent with stereotypes about their social categories or traits. Here, we explored such effects for a detectable, but not obvious, social group distinction: male sexual orientation. Bridging previous work on prejudice and occupational success with that on social perception, we found that perceivers rated gay and straight men as more suited to professions consistent with stereotypes about their groups (nurses, pediatricians, and English teachers vs. engineers, managers, surgeons, and math teachers) from mere photos of their faces. Notably, distinct evaluations of the gay and straight men emerged based on perceptions of their faces with no explicit indication of sexual orientation. Neither perceivers' expertise with hiring decisions nor diagnostic information about the targets eliminated these biases, but encouraging fair decisions did contribute to partly ameliorating the differences. Mediation analysis further showed that perceptions of the targets' sexual orientations and facial affect accounted for these effects. Individuals may therefore infer characteristics about individuals' group memberships from their faces and use this information in a way that meaningfully influences evaluations of their suitability for particular jobs. (PsycINFO Database Record PMID- 27559625 TI - When "embedded" means "stuck": Moderating effects of job embeddedness in adverse work environments. AB - Job embeddedness is predominately assumed to benefit employees, work groups, and organizations (e.g., higher performance, social cohesion, and lower voluntary turnover). Challenging this assumption, we examined the potentially negative outcomes that may occur if employees are embedded in an adverse work environment feeling "stuck," yet unable to exit a negative situation. More specifically, we considered two factors representing adverse work conditions: abusive supervision and job insecurity. Drawing from conservation of resources theory, we hypothesized that job embeddedness would moderate the relationship between these conditions and outcomes of voluntary turnover, physical health, emotional exhaustion, and sleep quality/quantity, such that employees embedded in more adverse environments would be less likely to quit, but would experience more negative personal outcomes. Results from two independent samples, one in Japan (N = 597) and one in the United States (N = 283), provide support for the hypothesized pattern of interaction effects, thereby highlighting a largely neglected "dark side" of job embeddedness. (PsycINFO Database Record PMID- 27559626 TI - Techno-economic analysis of a transient plant-based platform for monoclonal antibody production. AB - Plant-based biomanufacturing of therapeutic proteins is a relatively new platform with a small number of commercial-scale facilities, but offers advantages of linear scalability, reduced upstream complexity, reduced time to market, and potentially lower capital and operating costs. In this study we present a detailed process simulation model for a large-scale new "greenfield" biomanufacturing facility that uses transient agroinfiltration of Nicotiana benthamiana plants grown hydroponically indoors under light-emitting diode lighting for the production of a monoclonal antibody. The model was used to evaluate the total capital investment, annual operating cost, and cost of goods sold as a function of mAb expression level in the plant (g mAb/kg fresh weight of the plant) and production capacity (kg mAb/year). For the Base Case design scenario (300 kg mAb/year, 1 g mAb/kg fresh weight, and 65% recovery in downstream processing), the model predicts a total capital investment of $122 million dollars and cost of goods sold of $121/g including depreciation. Compared with traditional biomanufacturing platforms that use mammalian cells grown in bioreactors, the model predicts significant reductions in capital investment and >50% reduction in cost of goods compared with published values at similar production scales. The simulation model can be modified or adapted by others to assess the profitability of alternative designs, implement different process assumptions, and help guide process development and optimization. PMID- 27559627 TI - Zinc Toxicity Because of Denture Adhesive. PMID- 27559628 TI - When I Practiced With Flo: My Look Across the Generations of Nursing. PMID- 27559629 TI - An empirical analysis of ethical and professional issues in physicians' advertising: A comparative cross-sectional study. AB - The purpose of this study is to investigate current attitudes and opinions of physicians' advertising and to compare them to the attitudes expressed 10 years previously. This study was designed to determine (a) consumers' attitudes toward advertising by physicians, and (b) whether age, occupation, income, education, or sex of consumer accounted for any significant difference in attitudes toward physicians who advertise. The study seems to confirm the belief of many marketing professionals that advertising and marketing do not have a place in the management and operation of professional services. PMID- 27559630 TI - Adeno-associated virus and lentivirus vectors: a refined toolkit for the central nervous system. AB - The last two decades have witnessed the increasing instrumentalization of viruses, which have progressively evolved into highly potent gene transfer vehicles for a wide spectrum of applications. In the context of the central nervous system (CNS), their unique gene delivery features and targeting specificities have been exploited not only to improve our understanding of basic neurobiology, but also to investigate diseases or deliver therapeutic candidates. As a result, we have started moving away from the opportunistic use of recombinant vectors that are derived from naturally existing viruses toward the rational engineering of tailored lentivirus (LV) and adeno-associated virus (AAV) vectors for specific use in the CNS. PMID- 27559631 TI - African-American representation in family and twin studies of mood and anxiety disorders: A systematic review. AB - PURPOSE: Mood and anxiety disorders are common and disabling psychiatric disorders with known heritable risk factors. But the extent to which their heritability and familial risks can be generalized across ethnic/racial groups is still largely unknown, but remains of considerable scientific and clinical interest. The main objective in this review was to evaluate African-American (AA) representation in family and twin studies of major mood and anxiety disorders. METHOD: We conducted key word-driven computerized searches in MEDLINE and PsycINFO and manual searches from reference lists of selected articles. Search parameters included family or twin studies, mood or anxiety disorders, and familial aggregation or heritability. US-based studies published from 1980 to 2015 were included. RESULTS: The final selection yielded 209 studies, of which 88 did not report race/ethnicity or only reported Caucasian/white race. Of the remaining 121 studies, 66% did not include AAs, 24% included 1-10% AA, 8% included greater than 10% AA and 2 studies were exclusively AA. These trends were similar across study type, disorder and time periods spanning 35 years. LIMITATIONS: Small samples, including the large number of studies without race/ethnicity reports, limited detailed analyses of change across time by disorder and study type. Adoption studies were not included in this review. CONCLUSIONS: Underrepresentation of AAs in family and twin studies of affective disorders is substantial and can limit generalizability of established heritability and familial risk estimates across clinical and research settings. Additional twin and family studies focusing on AAs can be of benefit in closing this gap. PMID- 27559633 TI - Health Literacy and Palliative Care: Workshop Summary. PMID- 27559632 TI - Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression. AB - BACKGROUND: The amygdala is a key region in emotion processing, and studies have suggested that amygdala-frontal functional connectivity deficits could be modulated by antidepressants in major depressive disorder (MDD). Transcutaneous vagus nerve stimulation (tVNS), a non-invasive, peripheral neuromodulation method at the ear, has shown promising results in treating major depressive disorder (MDD) in several pilot studies. However, the neural mechanism underlying tVNS treatment of depression has not been fully investigated. In this study, we investigated how tVNS can modulate the amygdala-lateral prefrontal network resting state functional connectivity (rsFC) in mild or moderate major depressive disorder (MDD) patients. METHODS: Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments for four weeks. Resting state fMRI scans were applied before and after treatments. RESULTS: After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) scores were reduced significantly in the tVNS group as compared with the sham tVNS group. The rsFC in the tVNS group between the right amygdala and left dorsolateral prefrontal cortex was increased compared with sham tVNS. All the rsFC increases were also associated with HAMD reduction as well as reductions in the anxiety and retardation HAMD subscales. CONCLUSIONS: tVNS can significantly modulate the amygdala-lateral prefrontal rsFC of MDD patients; our results provide insights into the brain mechanism of tVNS treatment for MDD patients. PMID- 27559678 TI - Effect of breaking up sedentary time with callisthenics on endothelial function. AB - Periods of prolonged sitting impairs endothelial function in lower limb conduit arteries, which is attenuated with physical activity breaks. The effect of activity breaks on upper limb arteries has not been examined. This study assessed changes in brachial artery endothelial function following either a prolonged sitting period or breaking up this sedentary time by performing sets of callisthenics exercises. Ten healthy participants (6 men) completed 2 conditions in a counterbalanced order: (a) 1-h 26-min sitting, or (b) breaking up this period every 20 min by performing a set of 5 callisthenics exercises. Brachial artery endothelial function was assessed via ultrasound using the flow-mediated dilation (FMD) technique prior to and following each condition, while brachial shear rate (SR) was acquired after each set of callisthenics. There was no significant change in FMD over time (P = 0.09) or between conditions (P = 0.12). Compared to sitting, brachial SR increased following each set of callisthenics, with a significant difference after the third break (Sit: 33.94 +/- 12.79 s-1; Callisthenics: 57.16 +/- 30.48 s-1, P = 0.02). Alterations in SR in the upper limbs suggest callisthenics may be an effective intervention to break up sedentary time and attenuate the potentially deleterious effects of prolonged sitting on cardiovascular health. PMID- 27559679 TI - A rapid and automated relocation method of an AFM probe for high-resolution imaging. AB - The atomic force microscope (AFM) is one of the most powerful tools for high resolution imaging and high-precision positioning for nanomanipulation. The selection of the scanning area of the AFM depends on the use of the optical microscope. However, the resolution of an optical microscope is generally no larger than 200 nm owing to wavelength limitations of visible light. Taking into consideration the two determinants of relocation-relative angular rotation and positional offset between the AFM probe and nano target-it is therefore extremely challenging to precisely relocate the AFM probe to the initial scan/manipulation area for the same nano target after the AFM probe has been replaced, or after the sample has been moved. In this paper, we investigate a rapid automated relocation method for the nano target of an AFM using a coordinate transformation. The relocation process is both simple and rapid; moreover, multiple nano targets can be relocated by only identifying a pair of reference points. It possesses a centimeter-scale location range and nano-scale precision. The main advantages of this method are that it overcomes the limitations associated with the resolution of optical microscopes, and that it is label-free on the target areas, which means that it does not require the use of special artificial markers on the target sample areas. Relocation experiments using nanospheres, DNA, SWCNTs, and nano patterns amply demonstrate the practicality and efficiency of the proposed method, which provides technical support for mass nanomanipulation and detection based on AFM for multiple nano targets that are widely distributed in a large area. PMID- 27559680 TI - Use of a mouse model to identify a blood biomarker for IFNgamma activity in pediatric secondary hemophagocytic lymphohistiocytosis. AB - Life-threatening cytokine release syndromes include primary (p) and secondary (s) forms of hemophagocytic lymphohistiocytosis (HLH). Below detection in healthy individuals, interferon gamma (IFNgamma) levels are elevated to measurable concentrations in these afflictions suggesting a central role for this cytokine in the development and maintenance of HLH. Mimicking an infection-driven model of sHLH in mice, we observed that the tissue-derived levels of IFNgamma are actually 500- to 2000-fold higher than those measured in the blood. To identify a blood biomarker, we postulated that the IFNgamma gene products, CXCL9 and CXCL10 would correlate with disease parameters in the mouse model. To translate this into a disease relevant biomarker, we investigated whether CXCL9 and CXCL10 levels correlated with disease activity in pediatric sHLH patients. Our data demonstrate that disease control in mice correlates with neutralization of IFNgamma activity in tissues and that the 2 chemokines serve as serum biomarkers to reflect disease status. Importantly, CXCL9 and CXCL10 levels in pediatric sHLH were shown to correlate with key disease parameters and severity in these patients. Thus, the translatability of the IFNgamma-biomarker correlates from mouse to human, advocating the use of serum CXCL9 or CXCL10 as a means to monitor total IFNgamma activity in patients with sHLH. PMID- 27559681 TI - Microbiome in the pathogenesis of cystic fibrosis and lung transplant-related disease. AB - Significant advances in culture-independent methods have expanded our knowledge about the diversity of the lung microbial environment. Complex microorganisms and microbial communities can now be identified in the distal airways in a variety of respiratory diseases, including cystic fibrosis (CF) and the posttransplantation lung. Although there are significant methodologic concerns about sampling the lung microbiome, several studies have now shown that the microbiome of the lower respiratory tract is distinct from the upper airway. CF is a disease characterized by chronic airway infections that lead to significant morbidity and mortality. Traditional culture-dependent methods have identified a select group of pathogens that cause exacerbations in CF, but studies using bacterial 16S rRNA gene-based microarrays have shown that the CF microbiome is an intricate and dynamic bacterial ecosystem, which influences both host immune health and disease pathogenesis. These microbial communities can shift with external influences, including antibiotic exposure. In addition, there have been a number of studies suggesting a link between the gut microbiome and respiratory health in CF. Compared with CF, there is significantly less knowledge about the microbiome of the transplanted lung. Risk factors for bronchiolitis obliterans syndrome, one of the leading causes of death, include microbial infections. Lung transplant patients have a unique lung microbiome that is different than the pretransplanted microbiome and changes with time. Understanding the host-pathogen interactions in these diseases may suggest targeted therapies and improve long-term survival in these patients. PMID- 27559682 TI - Gastrostomy tube placement in infants with congenital diaphragmatic hernia: Frequency, predictors, and growth outcomes. AB - BACKGROUND: Gastrostomy tube (G-tube) placement is a common intervention for newborns with severe feeding difficulties. Infants with congenital diaphragmatic hernia (CDH) are at high risk for feeding problems. Prevalence of G-tube placement and consequent nutritional outcomes of infants with CDH and G-tubes has not been described. AIMS: Determine factors associated with G-tube placement and growth in infants with congenital diaphragmatic hernia. STUDY DESIGN: Retrospective cohort study of infants with CDH to evaluate the association of G tube placement with risk factors using logistic regression. We also assessed the association between growth velocity and G-tube placement and other risk factors using linear regression. SUBJECTS: The subjects of the study were infants with CDH treated at Duke University Medical Center from 1997 to 2013. OUTCOME MEASURES: Weight gain in infants with CDH that had G-tube placement compared to those infants with CDH that did not. RESULT: Of the 123 infants with CDH, 85 (69%) survived and G-tubes were placed in 25/85 (29%) survivors. On adjusted analysis, extracorporeal membrane oxygenation (OR=11.26 [95% CI: 1.92-65.89]; P=0.01) and proton pump inhibitor use (OR=17.29 [3.98-75.14], P<=0.001) were associated with G-tube placement. Infants without G-tubes had a growth velocity of 6.5g/day (95% CI: 2.5-10.4) more than infants with G-tubes. CONCLUSION: Survivors with more complex inpatient courses were more likely to receive G tubes. Further investigation is needed to identify optimal feeding practices for infants with CDH. PMID- 27559683 TI - Fractional-Dose Inactivated Poliovirus Vaccine Immunization Campaign - Telangana State, India, June 2016. AB - Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV. PMID- 27559684 TI - Cost-effectiveness of pelvic exenteration for locally advanced malignancy. AB - BACKGROUND: The rising cost of healthcare is well documented. The purpose of this study was to determine the cost-effectiveness of pelvic exenteration (PE). METHODS: Consecutive patients referred for consideration of PE between 2008 and 2011 were recruited into a prospective non-randomized study that compared quality of life (QoL) between patients who did or did not undergo PE. Information on QoL and cost (in Australian dollars, AUD) was collected at baseline, during admission and up to 24 months after discharge. QoL data were converted into a utility-based measure. Quality-adjusted life-years (QALYs) were calculated. Bottom-up costing was performed. The incremental cost-effectiveness ratio (ICER) was calculated per life-year saved and per QALY. RESULTS: There were 174 patients with sufficient data for analysis. Of these, 139 underwent PE. R0 was achieved in 78.4 per cent of patients. The survival rate at 24 months after PE was 74.8 per cent compared with 43 per cent in those without exenteration (P = 0.001). Treatment costs were significantly higher for patients who had PE compared with those who did not (mean AUD 137 407 versus 79 174; P < 0.001). The ICER was AUD 124 147 (95 per cent c.i. 71 585 to 261 876) per life-year saved and AUD 227 330 (109 974 to 1 100 449) per QALY. Curative PE (R0) was found to be more cost-effective than non curative PE (R1/R2), with an ICER of AUD 101 518 (60 105 to 200 428) versus 390 712 (74 368 to 82 256 739) per life-year saved. CONCLUSION: Treatment of advanced pelvic cancers is expensive regardless of the treatment intent. For a cost difference of only AUD 58 000 (?38 264), PE offers a chance of cure, and improves survival and QoL. PMID- 27559685 TI - Creation of a Long-Acting Nanoformulated 2',3'-Dideoxy-3'-Thiacytidine. AB - BACKGROUND: Antiretroviral drug discovery and formulation design will facilitate viral clearance in infectious reservoirs. Although progress has been realized for selected hydrophobic integrase and nonnucleoside reverse transcriptase inhibitors, limited success has been seen to date with hydrophilic nucleosides. To overcome these limitations, hydrophobic long-acting drug nanoparticles were created for the commonly used nucleoside reverse transcriptase inhibitor, lamivudine (2',3'-dideoxy-3'-thiacytidine, 3TC). METHODS: A 2-step synthesis created a slow-release long-acting hydrophobic 3TC. Conjugation of 3TC to a fatty acid created a myristoylated prodrug which was encased into a folate-decorated poloxamer 407. Both in vitro antiretroviral efficacy in human monocyte-derived macrophages and pharmacokinetic profiles in mice were evaluated for the decorated nanoformulated drug. RESULTS: A stable drug formulation was produced by poloxamer encasement that improved monocyte-macrophage uptake, antiretroviral activities, and drug pharmacokinetic profiles over native drug formulations. CONCLUSIONS: Sustained release of long-acting antiretroviral therapy is a new therapeutic frontier for HIV/AIDS. 3TC depot formation in monocyte-derived macrophages can be facilitated through stable subcellular internalization and slow drug release. PMID- 27559686 TI - Serum Phosphate and Creatinine Levels in the First Year of Life in Infants Born to HIV-Positive Mothers Receiving Tenofovir-Based Combination Regimens During Pregnancy and Prolonged Breastfeeding in an Option B+ Program in Malawi. PMID- 27559687 TI - Thiazolobenzyne: a versatile intermediate for multisubstituted benzothiazoles. AB - Thiazolobenzyne, which is a benzyne species fused with a thiazole ring, was efficiently generated via an iodine-magnesium exchange reaction of an ortho iodoaryl triflate-type precursor using a trimethylsilylmethyl Grignard reagent as an activator. A wide range of arynophiles reacted efficiently with the thiazolobenzynes generated by this method to afford various multisubstituted benzothiazoles. PMID- 27559688 TI - The cholinergic system in the cerebellum: from structure to function. AB - The cerebellar cholinergic system belongs to the third type of afferent nerve fiber system (after the climbing and mossy fibers), and has important modulatory effects on cerebellar circuits and cerebellar-mediated functions. In this report, we review the cerebellar cholinergic system, including cholinergic origins and innervations, acetylcholine receptor expression and distributions, cholinergic modulations of neuronal firing and synaptic plasticity, the cholinergic role in cerebellar-mediated integral functions, and cholinergic changes during development and aging. Because some motor and mental disorders, such as cerebellar ataxia and autism, are accompanied with cerebellar cholinergic disorders, we also discuss the correlations between cerebellar cholinergic dysfunctions and these disorders. The cerebellar cholinergic input plays an important role in the modulation of cerebellar functions; therefore, cholinergic abnormalities could induce physiological dysfunctions. PMID- 27559689 TI - Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes. AB - Hypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models. PMID- 27559690 TI - Neuroprotective properties of mitochondria-targeted antioxidants of the SkQ-type. AB - In 2008, using a model of compression brain ischemia, we presented the first evidence that mitochondria-targeted antioxidants of the SkQ family, i.e. SkQR1 [10-(6'-plastoquinonyl)decylrhodamine], have a neuroprotective action. It was shown that intraperitoneal injections of SkQR1 (0.5-1 MUmol/kg) 1 day before ischemia significantly decreased the damaged brain area. Later, we studied in more detail the anti-ischemic action of this antioxidant in a model of experimental focal ischemia provoked by unilateral intravascular occlusion of the middle cerebral artery. The neuroprotective action of SkQ family compounds (SkQR1, SkQ1, SkQTR1, SkQT1) was manifested through the decrease in trauma induced neurological deficit in animals and prevention of amyloid-beta-induced impairment of long-term potentiation in rat hippocampal slices. At present, most neurophysiologists suppose that long-term potentiation underlies cellular mechanisms of memory and learning. They consider inhibition of this process by amyloid-beta1-42 as an in vitro model of memory disturbance in Alzheimer's disease. Further development of the above studies revealed that mitochondria targeted antioxidants could retard accumulation of hyperphosphorylated tau protein, as well as amyloid-beta1-42, and its precursor APP in the brain, which are involved in developing neurodegenerative processes in Alzheimer's disease. PMID- 27559691 TI - Next-generation osmotic gradient ektacytometry for the diagnosis of hereditary spherocytosis: interlaboratory method validation and experience. AB - BACKGROUND: Osmotic gradient ektacytometry is part of the laboratory diagnosis process of hereditary spherocytosis (HS) and other red blood cell (RBC) membrane disorders. We here present the experience of two independent institutions with a next-generation ektacytometer, the LoRRca MaxSis analyzer, in HS diagnostic settings. METHODS: Inter- and intra-assay variability and sample stability were analyzed. Samples from patients with HS (n=40), probable HS (n=21), auto-immune hemolytic anemia (n=7), and other pathologies (n=37) were studied. Daily controls were run in parallel with patient samples. Results were expressed as percent of change compared to mean of controls. RESULTS: Analytical performances showed an inter-assay variability between 0.2% and 3%. Samples were stable for 48-72 h depending of temperature storage and anticoagulant used. The following diagnostic cut-offs were established for HS: an increase of more than 21.5% for the osmolality point at the minimal elongation index (O min), a decrease of more than 8.5% for the maximal elongation index (EI max), and a decreased area under the curve (AUC) of more than 18.5% compared to the mean of controls. CONCLUSIONS: As the previous instrument, the next-generation ektacytometer is an efficient tool for laboratory diagnosis of HS. Sample stability and standardized reporting of results allow inter-laboratory exchange and comparison. The most useful parameters for HS diagnosis were AUC, EI max, and O min; unfortunately, this method does not differentiate between HS and auto-immune hemolytic anemia (AIHA), but it distinguishes HS from other hereditary membrane pathologies. It can thus be considered as an intermediate step between screening and diagnostic tests. PMID- 27559692 TI - Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma. AB - BACKGROUND: Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids. METHODS: We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes. RESULTS: NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 MUg/L and from 0.3 to 860 MUg/L; those of COT between 52.8 and 110 MUg/L and from 33.8 to 94.7 MUg/L; and those of 3-HCOT between 12.4 and 23.5 MUg/L and from 8.5 to 24.4 MUg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration. CONCLUSIONS: The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies. PMID- 27559693 TI - Analysis of hemolysis, icterus and lipemia in arterial blood gas specimens. PMID- 27559694 TI - Regioselective Dichlorination of a Non-Activated Aliphatic Carbon Atom and Phenolic Bismethylation by a Multifunctional Fungal Flavoenzyme. AB - The regioselective functionalization of non-activated carbon atoms such as aliphatic halogenation is a major synthetic challenge. A novel multifunctional enzyme catalyzing the geminal dichlorination of a methyl group was discovered in Aspergillus oryzae (Koji mold), an important fungus that is widely used for Asian food fermentation. A biosynthetic pathway encoded on two different chromosomes yields mono- and dichlorinated polyketides (diaporthin derivatives), including the cytotoxic dichlorodiaporthin as the main product. Bioinformatic analyses and functional genetics revealed an unprecedented hybrid enzyme (AoiQ) with two functional domains, one for halogenation and one for O-methylation. AoiQ was successfully reconstituted in vivo and in vitro, unequivocally showing that this FADH2 -dependent enzyme is uniquely capable of the stepwise gem-dichlorination of a non-activated carbon atom on a freestanding substrate. Genome mining indicated that related hybrid enzymes are encoded in cryptic gene clusters in numerous ecologically relevant fungi. PMID- 27559695 TI - Clinical Evaluation of "Shock Bowel" Using Intestinal Fatty Acid Binding Protein. AB - "Shock bowel" is one of the computed tomographic (CT) signs of hypotension, yet its clinical implications remain poorly understood. We evaluated how shock bowel affects clinical outcomes and the extent of intestinal epithelial damage in trauma patients by measuring the level of intestinal fatty acid binding protein (I-FABP). We reviewed the initial CT scans, taken in the emergency room, of 92 patients with severe blunt torso trauma who were consecutively admitted during a 24-month period. The data collected included CT signs of hypotension, I-FABP, feeding intolerance, and other clinical outcomes. Demographic and clinical outcomes were compared in patients with and without hemodynamic shock and shock bowel. Shock bowel was found in 16 patients (17.4%); of them 7 patients (43.8%) did not have hemodynamic shock. Certain CT signs of hypotension, namely free peritoneal fluid, contrast extravasation, small-caliber aorta, and shock bowel, were significantly more common in patients with hemodynamic shock than in patients without (P < 0.05). Injury severity score and the rate of consciousness disturbance were significantly higher in patients with shock bowel than in patients without (P < 0.05). The rate of feeding intolerance and median plasma I FABP levels were significantly higher in patients with shock bowel than in patients without (75.0% vs. 22.4%, P < 0.001 and 17.0 ng/mL vs. 3.7 ng/mL, P < 0.001, respectively). There was no difference in mortality. In conclusion, shock bowel is not always due to hemodynamic shock. It does, however, indicate severe intestinal mucosal damages and may predict feeding intolerance. PMID- 27559696 TI - Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation. AB - Liver function deterioration is a major cause of death in variceal bleeding. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with biliary cirrhosis (CBDL), and CBDL rats pretreated with three doses (5 mg * kg * day) of simvastatin. Rats were submitted to H/R or sham procedure. Subsequently, livers were isolated and perfused for functional assessment of liver microcirculation. Liver transcriptome was assessed with microarrays. H/R significantly impaired endothelial-dependent vasorelaxation in cirrhotic (P = 0.035) but not control livers. H/R induced a similar increase in ALT in control and cirrhotic rats, whereas the increase in AST was 10 times higher in cirrhotic than in control rats (P = 0.007). Simvastatin prevented the impairment in endothelial-dependent vasorelaxation induced by H/R, and reduced by half the increase in ALT and AST (P < 0.05). Transcriptomics showed a marked upregulation of genes related to inflammatory response after H/R in cirrhotic livers, but not in controls, and this was blunted by simvastatin. In conclusion, H/R aggravates liver microvascular dysfunction in cirrhosis, and upregulates liver inflammatory pathways. This does not occur in control livers. Simvastatin prevented H/R-induced liver endothelial dysfunction, and attenuated liver injury and liver inflammatory response, suggesting that it might have potential for protecting the cirrhotic liver during bleeding complications. PMID- 27559698 TI - Early Coagulopathy is Associated With Increased Incidence of Ventilator Associated Events Among Burn Patients. AB - OBJECTIVE: Coagulopathy is known to be associated with burn injury. Our group has shown that, in spinal cord injury patients, coagulopathy is associated with an increase in ventilator-associated pneumonia (VAP). We hypothesized that the same association exists between coagulopathic burn patients and ventilator-associated events. METHODS: Patients admitted for burn care between January 1, 2011 and December 31, 2015 who required mechanical ventilation were included in the study. Ventilator-associated events (VAEs) as defined by the Center for Disease Control were categorized as no event, ventilator-associated condition, infection-related ventilator-associated complication, and possible VAP. Demographic, injury characteristics were compared among four international normalized ratio (INR) categories using analysis of variance and chi-square tests. RESULTS: Four hundred four patients were admitted for burn care, of whom 263 met the inclusion criteria. One hundred eleven had normal INR, 59 had a slightly elevated INR (1.2 1.4), 33 had a moderately elevated INR (1.4-1.6), and 60 had a severely elevated INR (>1.6). Those with moderately and severely elevated INR were ventilated for a longer period (P = 0.0034), had more days in the ICU (P = 0.0010), and had longer hospital stay (P = 0.0016). After adjusting for inhalation injury and total body surface area, patients with severely elevated INR were over four times as likely to have any VAE (OR: 4.16, 95% CI: 1.33-13.05) and 4.5 times as likely to develop infection-related ventilator-associated complication or possible ventilator associated pneumonia combined (OR: 4.59, 1.35-15.67). CONCLUSIONS: Early coagulopathy is associated with a significantly increased incidence of VAEs in burn patients. While additional studies need to be conducted to verify these findings, early recognition and treatment could decrease VAEs. PMID- 27559697 TI - Hepatoprotective Effects of Corilagin Following Hemorrhagic Shock are Through Akt Dependent Pathway. AB - Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague-Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-alpha, intercellular adhesion molecule-1, and cytokine induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway. PMID- 27559699 TI - Hypercholesterolemia Abrogates Remote Ischemic Preconditioning-Induced Cardioprotection: Role of Reperfusion Injury Salvage Kinase Signals. AB - Remote ischemic preconditioning (RIPC) is one of the most powerful intrinsic cardioprotective strategies discovered so far and experimental data indicate that comorbidity may interfere with the protection by RIPC. Therefore, we investigate whether RIPC-induced cardioprotection was intact in hypercholesterolemic rat hearts exposed to ischemia reperfusion in vivo. Normal or hypercholesterolemic rat hearts were exposed to 30 min of ischemia and 2 h of reperfusion, with or without RIPC, PI3K inhibitor wortmannin, MEK-ERK1/2 inhibitor PD98059, GSK3beta inhibitor SB216763. Infarct size, apoptosis, MG53, PI3K-p85, p-Akt, p-ERK1/2, p GSK3beta, and cleaved Caspase-3 were determined. RIPC reduced infarct size, limited cardiomyocyte apoptosis following IR that was blocked by wortmannin but not PD98059. RIPC triggered unique cardioprotective signaling including MG53, phosphorylation of Akt, and glycogen synthase kinase-3beta (GSK3beta) in concert with reduced proapoptotic active caspase-3. In contrast, RIPC failed to reduce myocardial necrosis and apoptosis as well as to increase the phosphorylated Akt and GSK3beta in hypercholestorolemic myocardium. Importantly, we found that inhibition of GSK with SB216763 reduced myocardial infarct size in healthy and hypercholesterolemic hearts, but no additional cardioprotective effect was achieved when combined with RIPC. Our results suggest that acute GSK3beta inhibition may provide a novel therapeutic strategy for hypercholesterolemic patients during acute myocardial infarction, whereas RIPC is less effective due to signaling events that adversely affect GSK3beta. PMID- 27559700 TI - FTY720-Induced Lymphopenia Does Not Aggravate Mortality in a Murine Model of Polymicrobial Abdominal Sepsis. AB - BACKGROUND: FTY720 is an immunosuppressive molecule licensed for the treatment of chronic relapsing multiple sclerosis (MS). It attenuates the adaptive immune response by sequestering T cells within secondary lymphoid organs via its action as functional antagonist of sphingosine-1-phasphate. To date, it is unknown whether FTY-induced lymphopenia puts MS patients at increased risk for severe forms of postoperative infectious complications such as abdominal sepsis. OBJECTIVES: To determine the effect of FTY720-induced lymphopenia on survival to sepsis secondary to postoperative intraabdominal infections in a murine model of polymicrobial sepsis. METHODS: Detailed analysis of cellular dynamics in secondary lymphoid organs and of cytokine profiles was performed in FTY720 treated or placebo-treated C57BL/6 mice after induction of colon ascendens stent peritonitis (CASP). Furthermore, survival analysis was performed in FTY720 treated and placebo-treated animals in severe CASP. Fifty percent of each group were treated with broad spectrum antibiotics. RESULTS: FTY720 treatment resulted in remodeling of cell populations present in the peripheral blood, the peritoneal cavity, and the spleen after CASP induction. Both lymphoid and myeloid cell lines were affected. However, survival in lymphopenic FTY720-treated animals was similar to placebo-treated mice following CASP. Antibiotic treatment increases survival in untreated as well as FTY720-treated animals to a similar extent. DISCUSSION: Our data demonstrate that inhibition of T-cell migration and induction of peripheral lymphopenia did not affect survival in a model of severe murine sepsis. The presence of reduced T- and B-cell numbers in the peripheral blood during a septic challenge did not negatively affect sepsis mortality in our model of severe abdominal sepsis. The absence of increased mortality under FTY720 treatment in the CASP model suggests that FTY720 treatment will probably not result in increased mortality in MS patients suffering from sepsis. PMID- 27559701 TI - Usefulness of the Delta Neutrophil Index as a Promising Prognostic Marker of Acute Cholangitis in Emergency Departments. AB - PURPOSE: Recent technological advances have led to analyses of the delta neutrophil index (DNI), which reflects the fraction of circulating immature granulocytes, using specific automated blood cell analyzers. We evaluated the significance of the DNI as a prognostic marker for early severity in patients with acute cholangitis. METHODS: We retrospectively analyzed patients initially diagnosed with acute cholangitis at emergency department admission, followed by diagnostic confirmation, during a set period. The DNI was determined on each day of hospitalization. Clinical outcomes were the incidence of shock requiring vasopressor/inotrope and 28-day mortality. RESULTS: We included 461 patients who met our inclusion criteria. According to multivariate Cox proportional hazard models, higher DNI at admission (hazard ratio [HR]: 1.102; 95% confidence interval [CI]: 1.053-1.153; P < 0.001), day 1 (HR: 1.069; 95% CI: 1.018-1.122; P = 0.008), and day 2 (HR: 1.118; 95% CI: 1.053-1.186; P < 0.001) were significant risk factors for 28-day mortality. Among patients with acute cholangitis, a DNI > 4.9% at admission (HR: 5.632; 95% CI: 1.977-16.045; P = 0.001) and day 1 (HR, 9.973; 95% CI: 2.666-37.302; P < 0.001) and higher DNI ( > 2.5%) on day 2 (HR, 16.942; 95% CI: 2.15-133.496; P = 0.007) were associated with increased 28-day mortality. CONCLUSION: Higher DNI levels are predictive markers of hemodynamic instability and 28-day mortality in patients with acute cholangitis. The accuracy of DNI for predicting hemodynamic instability and 28-day mortality is superior to that of other parameters. PMID- 27559702 TI - Apolipoprotein L Expression Correlates with Neutrophil Cell Death in Critically Ill Patients. AB - Delayed neutrophil apoptosis has been demonstrated in sepsis and may contribute to organ damage. It has recently been proposed that apolipoprotein L (ApoL) may be involved in programmed cell death, but the expression and functions of ApoLs in leukocytes (especially neutrophils) during sepsis and other inflammatory conditions are currently unknown. In this prospective observational study in a 36 bed university hospital medicosurgical intensive care unit (ICU), we included 78 adult ICU patients with (n = 41) or without (n = 37) sepsis and 47 healthy volunteers. We analyzed ApoL mRNA expression using quantitative polymerase chain reaction in whole blood leukocytes and protein expression in CD15 isolated neutrophils using Western blotting. Neutrophil apoptosis was assessed using the APO-BRDU method. Apolipoprotein L mRNA was downregulated in whole blood leukocytes and neutrophils in ICU patients compared with in healthy volunteers, and this effect translated at the protein level as indicated by Western blot analysis of neutrophils. There was a negative correlation between ApoL expression in neutrophils and C-reactive protein levels and a positive correlation between the number of apoptotic neutrophils and mRNA levels of ApoL1 and ApoL2. The degree of neutrophil apoptosis in critically ill patients is therefore correlated with modified expression profiles of ApoLs. PMID- 27559703 TI - Role of the Purinergic Receptor P2XR4 After Blunt Chest Trauma in Cigarette Smoke Exposed Mice. AB - Both acute and chronic lung injury are associated with up-regulation of the pulmonary expression of the purinergic receptors P2XR4 and P2XR7. Genetic deletion or blockade of P2XR7 attenuated pulmonary hyperinflammation, but simultaneous P2XR4 up-regulation compensated for P2XR7 deletion. Therefore, we tested the hypothesis whether genetic P2XR4 deletion would attenuate the pulmonary inflammatory response and thereby improve organ function after blunt chest trauma in mice with and without pretraumatic cigarette smoke (CS) exposure.After 3 weeks to 4 weeks of exposure to CS, anesthetized wildtype or P2XR4 mice (n = 32) underwent a blast wave-induced blunt chest trauma followed by 4 h of lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline support to maintain mean arterial pressure >55 mm Hg. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1, B-cell lymphoma-extra large (Bcl-xL), endogenous nuclear factor-kappaB inhibitor (IkappaBalpha) expression, nitrotyrosine formation, purinergic receptor expression, and histological scoring.Despite a significant increase in the histopathology score in both CS-exposed groups, neither CS exposure nor P2XR4 deletion had any significant effect on post-traumatic pulmonary function and inflammatory response. However, P2XR4 deletion was associated with attenuated impairment of glucose homeostasis and acid-base-status after CS exposure and chest trauma.In conclusion, genetic P2XR4 deletion failed to attenuate the acute post-traumatic pulmonary inflammatory response. The improved glucose homeostasis and acid-base-status after CS exposure in the P2XR4 group was possibly due to less alveolar hypoxia-induced right ventricular remodeling resulting in preserved liver metabolic capacity. PMID- 27559704 TI - Renal simplicity denervation reduces blood pressure and renal injuries in an obesity-induced hypertension dog model. AB - This study aimed to investigate the effects of renal sympathetic denervation (RDN) on blood pressure, renal function, and renal tissue pathological changes in obesity-induced hypertensive dogs. Thirty-two beagle dogs (10-12 months) were randomized to the control (n=10) and model groups (n=22). High-fat diet (HFD) was used to establish the obesity-induced hypertensive model. After 3 months of HFD, 20 animals with successfully induced hypertension were randomized to the RDN (n=10) and sham groups (n=10). Renal artery angiography, body weight, blood pressure, heart rate (HR), and blood and urine biochemistry were determined 1, 3 and 6 months after surgery. Models were killed 6 months after surgery. Pathological changes in the renal artery and renal tissue were assessed. The HFD group had significantly (P<.05) increased body weight, HR, and blood pressure, and higher levels of urine albumin, serum noradrenaline, and angiotensin II compared with controls. After RDN, blood pressure was decreased compared with baseline and the sham group (P<.05). In the RDN group, examination of the renal artery and renal tissue showed intact intima of renal artery in the surgical area, renal sympathetic nerve degeneration, necrosis, and dissolution, and widened space between nerve fibres. Hypertension-induced renal pathological changes were mild to moderate in the RDN group, but severe in the sham group. The control group had normal glomerular structure. In conclusion, RDN can effectively lower blood pressure in obesity-induced hypertensive dogs, as well as hypertension-induced renal pathological changes. PMID- 27559705 TI - Polycystic ovary syndrome and environmental toxins. AB - Polycystic ovary syndrome (PCOS) is the most common, heterogeneous, and multifactorial endocrine disorder in premenopausal women. The pathophysiology of this endocrinopathy is still unclear; however, the heterogeneity of its features within ethnic races, geographic location, and families suggests that environment and lifestyle are of prime importance. This work is mainly focused on the possible role of the most common and studied environmental toxins for this syndrome in the pathogenesis of PCOS. Plasticizers, such as bisphenol A (BPA) or phthalates, which belong to the categories of endocrine disrupting chemicals (EDCs) and advanced glycation end products (AGEs), affect humans' health in everyday, industrialized life; therefore special attention should be paid to such exposure. Timing of exposure to EDCs is crucial for the intensity of adverse health effects. It is now evident that fetuses, infants, and/or young children are the most susceptible groups, especially in the early development periods. Prenatal exposure to EDCs that mimic endogenous hormones may contribute to the altered fetal programming and in consequence lead to PCOS and other adverse health effects, potentially transgenerationally. Acute or prolonged exposure to EDCs and AGEs through different life cycle stages may result in destabilization of the hormonal homeostasis and lead to disruption of reproductive functions. They may also interfere with metabolic alterations such as obesity, insulin resistance, and compensatory hyperinsulinemia that can exacerbate the PCOS phenotype and contribute to PCOS consequences such as type 2 diabetes and cardiovascular disease. Since wide exposure to environmental toxins and their role in the pathophysiology of PCOS are supported by extensive data derived from diverse scientific models, protective strategies and strong recommendations should be considered to reduce human exposure to protect present and future generations from their adverse health effects. PMID- 27559706 TI - Respiratory Failure in a Woman 8 Months After an Allogeneic Stem Cell Transplant. PMID- 27559707 TI - Designing optimal HIV-vaccine T-cell responses. AB - PURPOSE OF REVIEW: T cells can efficaciously control HIV replication, and it has been hypothesized that inducing those responses before exposure occurs may prevent HIV infection. However, conventional attempts to generate protective CD8 T-cell responses against HIV have generally failed. Based on current knowledge from chronic HIV infection and previous vaccine trials, this review details optimal CD8 and CD4 T-cell response design that may confer protection from HIV infection. RECENT FINDINGS: The failure of two vaccines geared toward inducing T cell response (STEP trial and HVTN505/Phambili) as well as the modest protection of the RV144 that mainly demonstrated nonneutralizing antibodies to be a correlate of protection have rattled the idea that a pure T-cell-based vaccine may induce protection. Moreover, in the recent years, CD4 T cells, and in particular the T follicular helper cell subset, received attention as a critical component for T-cell-inducing and antibody-inducing vaccines. SUMMARY: It is apparent that all vaccines depend for their efficacy on a cellular component either to directly kill virally infected cells or to provide important helper signals for the development of efficacious B-cell responses. Recent vaccine trials have had a major impact on the field and are guiding new approaches for HIV vaccine design. PMID- 27559708 TI - The first 24 h: targeting the window of opportunity for antibody-mediated protection against HIV-1 transmission. AB - PURPOSE OF REVIEW: I will review evidence that antibodies protect against HIV-1 transmission in a short window of opportunity, involving neutralization, Fc mediated effector function, or both. RECENT FINDINGS: The last decade witnessed a dramatic progress in the understanding of antibody-mediated protection against HIV-1, including active and passive immunization studies in nonhuman primates; association between reduced infection risk and the specificities and function of antibodies in the RV144 clinical trial; identification of potent, broadly neutralizing antibodies; high-resolution structural studies of the HIV-1 envelope trimer; and an increasing appreciation that Fc-mediated effector function is critical to protection against transmission for neutralizing and nonneutralizing antibodies. Less information is known about how antibodies protect in situ, except that they must do in the first 24 h after exposure. New evidence suggests that antibodies protect in an acute innate immune environment involving the NXLRX1 inflammasome and transforming growth factor beta (TGF-beta) that favors infection and rapid dissemination of CCR6RORgamma Th17 cells. SUMMARY: These recent findings set the stage for understanding how antibodies can prevent the transmission of HIV-1. In this context, antibodies must prevent infection in an innate immune environment that strongly favors transmission. This information is key for the development of a vaccine against HIV-1. PMID- 27559709 TI - Approaches to the induction of HIV broadly neutralizing antibodies. AB - PURPOSE OF REVIEW: A vaccine that elicits antibody responses that can neutralize the diversity of HIV clades has not yet been achieved, and is a major focus of HIV vaccine research. Here, we provide an update on the barriers to eliciting such antibodies, and how advances in immunogen design may circumvent these roadblocks, focusing on data published in the last year. RECENT FINDINGS: Studies of how broadly neutralizing antibodies (bNAbs) develop in HIV-infected donors continue to produce key insights, suggesting that for some viral targets there are common pathways to developing breadth. Germline-targeting strategies, that aim to recruit rare precursors of bNAbs, have shown promise in immunogenicity studies, and structural biology has led to advances in immunogen design. Mapping of strain-specific tier 2 vaccine responses has highlighted the challenges that remain in driving antibodies toward breadth. SUMMARY: Elucidation of the HIV envelope structure, together with an understanding of how bNAbs emerge in vivo has guided the design of new immunogens and vaccine strategies that show promise for eliciting protective antibodies. PMID- 27559711 TI - Cancer clinical trials in persons with HIV infection. AB - PURPOSE OF REVIEW: The era of modern HIV therapeutics is well underway. The cancer and infectious disease epidemiology of HIV disease has markedly altered as populations are availed to the benefits of antiretroviral therapy (ARV). The types of cancers occurring among those with HIV infection has broadened but the case burden in absolute numbers is very low relative to the background population. There are fewer incident cases of the AIDS-defining cancers (aggressive B-cell lymphomas, Kaposi's sarcoma, and cervical cancer). There is an increased risk for certain non-AIDS-defining cancers, but these occur somewhat sporadically relative to clinical trial enrollment. The changing epidemiology of cancer in HIV poses challenges as well as opportunities for participation of persons with HIV in cancer therapy clinical trials. RECENT FINDINGS: There are excellent examples of cancer trials that inform cancer therapy for patients with HIV infection. Examples include those from HIV-specific trials and from trials mainly focused on the background population that included patients with HIV infection. SUMMARY: Interpretation of clinical trials to guide therapy for those with HIV infection and cancer largely depends on data that does not include HIV infected patients. The ability to extend clinical trial findings to populations not included in clinical trials remains problematic for a variety of populations, including those with HIV or AIDS. Careful prioritization of studies designed to bridge this gap is needed. However, there are published studies that serve as excellent examples bridging these gaps and the portfolio of cancer therapy trials underway will inform HIV and cancer better than at any time in the past. PMID- 27559710 TI - Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences. AB - PURPOSE OF REVIEW: Nonhuman primate (NHP) models of AIDS are powerful systems for evaluating HIV vaccine approaches in vivo. Authentic features of HIV-1 transmission, dissemination, target cell tropism, and pathogenesis, and aspects of anti-HIV-1 immune responses, can be recapitulated in NHPs provided the appropriate, specific model parameters are considered. Here, we discuss key model parameter options and their implications for HIV-1 vaccine evaluation. RECENT FINDINGS: With the availability of several different NHP host species/subspecies, different challenge viruses and challenge stock production methods, and various challenge routes and schemata, multiple NHP models of AIDS exist for HIV vaccine evaluation. The recent development of multiple new challenge viruses, including chimeric simian-human immunodeficiency viruses and simian immunodeficiency virus clones, improved characterization of challenge stocks and production methods, and increased insight into specific challenge parameters have resulted in an increase in the number of available models and a better understanding of the implications of specific study design choices. SUMMARY: Recent progress and technical developments promise new insights into basic disease mechanisms and improved models for better preclinical evaluation of interventions to prevent HIV transmission. PMID- 27559712 TI - Let's stay together? Intrinsic and extrinsic factors involved in pair bond dissolution in a recolonizing wolf population. AB - For socially monogamous species, breeder bond dissolution has important consequences for population dynamics, but the extent to which extrinsic or intrinsic population factors causes pair dissolution remain poorly understood, especially among carnivores. Using an extensive life-history data set, a survival analysis and competing risks framework, we examined the fate of 153 different wolf (Canis lupus) pairs in the recolonizing Scandinavian wolf population, during 14 winters of snow tracking and DNA monitoring. Wolf pair dissolution was generally linked to a mortality event and was strongly affected by extrinsic (i.e. anthropogenic) causes. No divorce was observed, and among the pair dissolution where causes have been identified, death of one or both wolves was always involved. Median time from pair formation to pair dissolution was three consecutive winters (i.e. approximately 2 years). Pair dissolution was mostly human-related, primarily caused by legal control actions (36.7%), verified poaching (9.2%) and traffic-related causes (2.1%). Intrinsic factors, such as disease and age, accounted for only 7.7% of pair dissolutions. The remaining 44.3% of dissolution events were from unknown causes, but we argue that a large portion could be explained by an additional source of human-caused mortality, cryptic poaching. Extrinsic population factors, such as variables describing the geographical location of the pair, had a stronger effect on risk of pair dissolution compared to anthropogenic landscape characteristics. Population intrinsic factors, such as the inbreeding coefficient of the male pair member, had a negative effect on pair bond duration. The mechanism behind this result remains unknown, but might be explained by lower survival of inbred males or more complex inbreeding effects mediated by behaviour. Our study provides quantitative estimates of breeder bond duration in a social carnivore and highlights the effect of extrinsic (i.e. anthropogenic) and intrinsic factors (i.e. inbreeding) involved in wolf pair bond duration. Unlike the effects of intrinsic and extrinsic factors that are commonly reported on individual survival or population growth, here we provide quantitative estimates of their potential effect on the social unit of the population, the wolf pair. PMID- 27559713 TI - Inferior vena cava filter insertion through the popliteal vein: enabling the percutaneous endovenous intervention of deep vein thrombosis with a single venous access approach in a single session. AB - PURPOSE: We aimed to evaluate the efficiency of placing an inferior vena cava (IVC) filter through the same popliteal vein access site used for percutaneous endovenous intervention in patients with extensive lower extremity deep vein thrombosis. METHODS: This retrospective study included 21 patients who underwent IVC filter insertion through the popliteal vein over a three-year period. Patient medical records were reviewed for the location of the deep vein thrombosis, result of filter removal, and total number of endovascular procedures needed for filter insertion and recanalization of the lower extremity venous system. Follow up lower extremity computed tomography (CT) venography was also reviewed in each patient to assess the degree of filter tilt in the IVC. RESULTS: All patients had extensive lower extremity deep vein thrombosis involving the iliac vein and/or femoral vein. Seventeen patients showed deep vein thrombosis of the calf veins. In all patients, IVC filter insertion and the recanalization procedure were performed during a single procedure through the single popliteal vein access site. In the 17 patients undergoing follow-up CT, the mean tilt angle of the filter was 7.14 degrees +/-4.48 degrees in the coronal plane and 8.77 degrees +/ 5.49 degrees in the sagittal plane. Filter retrieval was successful in 16 of 17 patients (94.1%) in whom filter retrieval was attempted. CONCLUSION: Transpopliteal IVC filter insertion is an efficient technique that results in low rates of significant filter tilt and enables a single session procedure using a single venous access site for filter insertion and percutaneous endovenous intervention. PMID- 27559714 TI - Endovascular occlusion of pulmonary arteriovenous malformations with the ArtVentive Endoluminal Occlusion SystemTM. AB - Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies of the lung and carry the risk of cerebral thromboembolism, brain abscess, or pulmonary hemorrhage. We describe a 64-year-old male with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) who presented with a five-year history of progressive effort dyspnea and a PAVM in the right upper lobe successfully treated by transcatheter embolization of feeding arteries using a new occlusion device, the ArtVentive Endoluminal Occlusion SystemTM. PMID- 27559715 TI - Rigid Tether Directed Regioselective Synthesis and Crystallographic Characterization of Labile 1,2,3,4-Bis(triazolino)[60]fullerene and Its Thermolized Derivatives. AB - Labile bis-triazoline adducts of C60 are supposed to be the precursors of bis azafulleroids, but the formation mechanism is still unclear because of the incomplete isolation of the thermolized products and the lack of X-ray structures. A rigid-tethered reagent 1,2-bis(azidomethyl)benzene (1) was used to regioselectively synthesize the labile 1,2,3,4-bis(triazolino)[60]-fullerene (2), the structure of which was determined by single-crystal X-ray crystallography. Further thermolysis of 2 produces four products (3 a-3 d), which were all characterized by X-ray crystallography. Although 3 a and 3 b have traditional bis azafulleroid structures, as proposed previously, 3 c and 3 d show unprecedented structures with either the coexistence of [5,6]-open and [6,6]-closed patterns or an oxidized structure with an 11-membered ring on the cage. A thermolysis mechanism is proposed to clarify long-term confusion about the transformation process from bis-triazoline adducts to bis-azafulleroids of C60 . PMID- 27559718 TI - Not only amblyopic but also dominant eye in subjects with strabismus show increased saccadic latency. AB - Amblyopia is a developmental disorder of vision usually associated with the presence of strabismus and/or anisometropia during early childhood. Subject literature has shown that both the amblyopic and fellow eyes (especially in strabismic subjects) may manifest a variety of perceptual and oculomotor deficits. Previous studies using simple saccadic responses (pro-saccades) showed an increased saccadic latency only for the amblyopic eye viewing conditions. So far, there have appeared no saccadic latency studies in strabismic amblyopia for more complex volitional saccades. In order to maximize the contribution of the central retina in the process of saccade initiation, we decided to use delayed saccadic responses in order to test the hypothesis about saccadic latency increase in both eyes in strabismic amblyopes. The results from our study have shown that saccadic latency is increased both in the dominant and amblyopic eyes. In addition, the amblyopic eye in the strabismic group showed greater increase in saccadic latency compared to an amblyopic eye in the anisometropic group from our previous study. The observed increase in saccadic reaction time for the dominant eye is novel and provides further evidence that the visual pathway associated with the dominant eye might be also impaired in strabismic amblyopia. Since an abnormal binocular input during visual system development may affect gaze stability in both eyes, we speculate that unsteady fixation accompanied with subtle perceptual deficits contribute to an increase in saccadic latency that is observed in the dominant eye. Moreover, it appears that the cortical processes related to saccade decisions are delayed both for amblyopic and fellow eyes in strabismic subjects. PMID- 27559717 TI - Early hyperoxia burden detected by cerebral near-infrared spectroscopy is superior to pulse oximetry for prediction of severe retinopathy of prematurity. AB - OBJECTIVE: Fractional tissue oxygen extraction (FTOE) is a measure derived from cerebral near-infrared spectroscopy (NIRS) and simultaneous pulse oximetry (SpO2), capturing the proportion of oxygen delivered in arterial blood that is used by the target tissue. FTOE may provide a better proxy measurement of retinal hyperoxia than pulse oximetry alone and could provide insight into the risk for retinopathy of prematurity (ROP). In this study, we directly compared hyperoxia burden calculated from FTOE with hyperoxia burden calculated from SpO2 alone in order to assess the strength of association between hyperoxia and severe ROP. STUDY DESIGN: Infants born before <30 weeks and weighing <1500 g underwent synchronized SpO2 and FTOE recording over the first 4 days following birth. After error correction of the raw recording, hyperoxia burden was calculated as the percentage of the total SpO2 or FTOE recording with measurements exceeding defined thresholds (90/93/95% and 20/15/10%, respectively) and was compared with the outcome of severe ROP, defined as ROP requiring laser therapy, after controlling for important covariates. RESULT: A total of 63 infants were included with a mean+/-s.d. gestational age of 25.8+/-1.5 weeks and birth weight of 898.5+/-206.9 g; 13/63 (20%) had severe ROP. SpO2 hyperoxia burden was not associated with severe ROP at any threshold. FTOE hyperoxia burden was associated with severe ROP at the 15% (P=0.04) and 10% (P=0.03) thresholds. Infants with severe ROP spent 20% and 50% more time exceeding the 15% and 10% thresholds, respectively, as compared with those without severe ROP. CONCLUSION: In the first 96 h of life, FTOE but not SpO2 hyperoxia burden is associated with severe ROP. These preliminary results suggest that NIRS may be a viable alternative technology for targeted oxygen saturation guidelines. PMID- 27559716 TI - A randomized controlled study of the efficacy of 4 weeks of supplementation with omega-3 polyunsaturated fatty acids in cases of unexplained oligohydramnios. AB - OBJECTIVE: To investigate the effect of omega-3 fatty acids on amniotic fluid volume and uterine artery blood flow after 4 weeks of treatment. STUDY DESIGN: A randomized clinical trial was conducted on 140 participants with unexplained oligohydramnios at Woman's Health Hospital, Assiut University, Egypt. Participants were randomly assigned to omega-3 plus capsules or placebo. Categorical variables were analyzed by means of the chi2 test, whereas continuous variables were analyzed by means of the independent-sample T-test between the two groups. RESULTS: One hundred and forty women were recruited. There was significant improvement in the amniotic fluid index (AFI) in the omega-3 plus group in comparison with the placebo group (P=0.001). Moreover, there were significant decreases in the systolic/diastolic ratio (P=0.01), resistance index (P=0.041) and pulsatility index (P=0.002) of the uterine arteries in the omega-3 plus group when comparing baseline values with those after 4 weeks. CONCLUSION: The results suggest that omega-3 fatty acids may have a role in the increase in AFI in cases of unexplained oligohydramnios. This effect may be secondary to the increase in uterine blood flow. PMID- 27559719 TI - Visual reinforcement shapes eye movements in visual search. AB - We use eye movements to gain information about our visual environment; this information can indirectly be used to affect the environment. Whereas eye movements are affected by explicit rewards such as points or money, it is not clear whether the information gained by finding a hidden target has a similar reward value. Here we tested whether finding a visual target can reinforce eye movements in visual search performed in a noise background, which conforms to natural scene statistics and contains a large number of possible target locations. First we tested whether presenting the target more often in one specific quadrant would modify eye movement search behavior. Surprisingly, participants did not learn to search for the target more often in high probability areas. Presumably, participants could not learn the reward structure of the environment. In two subsequent experiments we used a gaze-contingent display to gain full control over the reinforcement schedule. The target was presented more often after saccades into a specific quadrant or a specific direction. The proportions of saccades meeting the reinforcement criteria increased considerably, and participants matched their search behavior to the relative reinforcement rates of targets. Reinforcement learning seems to serve as the mechanism to optimize search behavior with respect to the statistics of the task. PMID- 27559720 TI - Template optimization and transfer in perceptual learning. AB - We studied how learning changes the processing of a low-level Gabor stimulus, using a classification-image method (psychophysical reverse correlation) and a task where observers discriminated between slight differences in the phase (relative alignment) of a target Gabor in visual noise. The method estimates the internal "template" that describes how the visual system weights the input information for decisions. One popular idea has been that learning makes the template more like an ideal Bayesian weighting; however, the evidence has been indirect. We used a new regression technique to directly estimate the template weight change and to test whether the direction of reweighting is significantly different from an optimal learning strategy. The subjects trained the task for six daily sessions, and we tested the transfer of training to a target in an orthogonal orientation. Strong learning and partial transfer were observed. We tested whether task precision (difficulty) had an effect on template change and transfer: Observers trained in either a high-precision (small, 60 degrees phase difference) or a low-precision task (180 degrees ). Task precision did not have an effect on the amount of template change or transfer, suggesting that task precision per se does not determine whether learning generalizes. Classification images show that training made observers use more task-relevant features and unlearn some irrelevant features. The transfer templates resembled partially optimized versions of templates in training sessions. The template change direction resembles ideal learning significantly but not completely. The amount of template change was highly correlated with the amount of learning. PMID- 27559721 TI - Diagnosis of subglottic stenosis in a rabbit model using long-range optical coherence tomography. AB - OBJECTIVES/HYPOTHESIS: Current imaging modalities lack the necessary resolution to diagnose subglottic stenosis. The aim of this study was to use optical coherence tomography (OCT) to evaluate nascent subglottic mucosal injury and characterize mucosal thickness and structural changes using texture analysis in a simulated intubation rabbit model. STUDY DESIGN: Prospective animal study in rabbits. METHODS: Three-centimeter-long sections of endotracheal tubes (ETT) were endoscopically placed in the subglottis and proximal trachea of New Zealand White rabbits (n = 10) and secured via suture. OCT imaging and conventional endoscopic video was performed just prior to ETT segment placement (day 0), immediately after tube removal (day 7), and 1 week later (day 14). OCT images were analyzed for airway wall thickness and textural properties. RESULTS: Endoscopy and histology of intubated rabbits showed a range of normal to edematous tissue, which correlated with OCT images. The mean airway mucosal wall thickness measured using OCT was 336.4 MUm (day 0), 391.3 MUm (day 7), and 420.4 MUm (day 14), with significant differences between day 0 and day 14 (P = .002). Significance was found for correlation and homogeneity texture features across all time points (P < .05). CONCLUSIONS: OCT is a minimally invasive endoscopic imaging modality capable of monitoring progression of subglottic mucosal injury. This study is the first to evaluate mucosal injury during simulated intubation using serial OCT imaging and texture analysis. OCT and texture analysis have the potential for early detection of subglottic mucosal injury, which could lead to better management of the neonatal airway and limit the progression to stenosis. LEVEL OF EVIDENCE: NA Laryngoscope, 127:64-69, 2017. PMID- 27559722 TI - Exploitation of endophytes for sustainable agricultural intensification. AB - Intensive agriculture, which depends on unsustainable levels of agrochemical inputs, is environmentally harmful, and the expansion of these practices to meet future needs is not economically feasible. Other options should be considered to meet the global food security challenge. The plant microbiome has been linked to improved plant productivity and, in this microreview, we consider the endosphere a subdivision of the plant microbiome. We suggest a new definition of microbial endophyte status, the need for synergy between fungal and bacterial endophyte research efforts, as well as potential strategies for endophyte application to agricultural systems. PMID- 27559723 TI - Benefits of Proper Hair Restoration. PMID- 27559725 TI - Dengue in the Context of the Integrated Management of Childhood Illness. PMID- 27559726 TI - Improving the Quality of the Reporting of Research Results. PMID- 27559724 TI - Individual differences in cognitive reappraisal use and emotion regulatory brain function in combat-exposed veterans with and without PTSD. AB - BACKGROUND: Veterans with posttraumatic stress disorder (PTSD) exhibit marked deficits in emotion regulation. Past research has demonstrated underengagement of the prefrontal cortex during regulation of negative affect in those with PTSD, but has been unable to find evidence of impaired downregulation of the amygdala. One possibility is that there exists variability in amygdala reactivity that cuts across diagnostic status and which can be characterized using a continuous measure of individual differences. In healthy/nontraumatized volunteers, individual variability in amygdala engagement during emotion processing and regulation has been shown to relate to habitual use of regulation strategies. METHODS: The current study examined whether self-reported use of cognitive reappraisal and expressive suppression regulation strategies correlated with brain activation during cognitive reappraisal in combat-exposed veterans with (n = 28) and without PTSD (combat-exposed controls, CEC; n = 20). RESULTS: Results showed that greater self-reported use of cognitive reappraisal was associated with less activation in the right amygdala during volitional attempts to attenuate negative affect using reappraisal, irrespective of PTSD diagnosis. CONCLUSIONS: This finding is in line with prior work and extends evidence of an association between habitual use of regulation strategies and amygdala engagement during emotion regulation to a trauma-exposed sample of individuals both with and without PTSD. Furthermore, by providing evidence of individual differences in regulation-related amygdala response in a traumatized sample, this result may increase understanding of the neural mechanisms that support variability in symptom manifestation observed across individuals with PTSD. PMID- 27559727 TI - Plasma Level of Placenta-Derived Macrophage-Stimulating Protein -Chain in Preeclampsia before 20 Weeks of Pregnancy. AB - OBJECT: This study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein alpha-chain (MSP-alpha) before the 20th week of gestation for the early diagnosis of preeclampsia (PE). METHODS AND MATERIALS: Two parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-alpha plasma level was measured before the 20th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group). RESULTS: The plasma level of MSP-alpha was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP alpha level before the 20th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-alpha before the 20th week of gestation was 0.905 (95% CI, 0.811-0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 +/- 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 +/- 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in the PE group (IOD [SUM]: 12192.65 +/- 5325.56 vs. 4104.83 +/- 2383.06, P = 0.021). CONCLUSION: According to the findings of this study, the plasma level of MSP-alpha may be associated with PE, and MSP-alpha may be considered a candidate protein for further analysis in studies of PE. Multicenter studies with larger sample sizes must be performed in the future to obtain accurate results regarding the predictive value of MSP alpha in combination with other protein factors for the early diagnosis of PE. PMID- 27559729 TI - Steering the development of interprofessional education. PMID- 27559728 TI - Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus. AB - Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40 degrees C, <=90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40 degrees C, <=90% non condensing humidity; and iv) minimal sample collection needs (50-100MUL, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions. PMID- 27559730 TI - Corrigendum. PMID- 27559732 TI - BEclear: Batch Effect Detection and Adjustment in DNA Methylation Data. AB - Batch effects describe non-natural variations of, for example, large-scale genomic data sets. If not corrected by suitable numerical algorithms, batch effects may seriously affect the analysis of these datasets. The novel array platform independent software tool BEclear enables researchers to identify those portions of the data that deviate statistically significant from the remaining data and to replace these portions by typical values reconstructed from neighboring data entries based on latent factor models. In contrast to other comparable methods that often use some sort of global normalization of the data, BEclear avoids changing the apparently unaffected parts of the data. We tested the performance of this approach on DNA methylation data for various tumor data sets taken from The Cancer Genome Atlas and compared the results to those obtained with the existing algorithms ComBat, Surrogate Variable Analysis, RUVm and Functional normalization. BEclear constantly performed at par with or better than these methods. BEclear is available as an R package at the Bioconductor project http://bioconductor.org/packages/release/bioc/html/BEclear.html. PMID- 27559731 TI - Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma. AB - Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/beta-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean +/- SE) showed that the expression of CD1 (3.9 +/- 0.5 vs 12.2 +/- 0.9), FRA1 (5.5 +/- 0.6 vs 16.8 +/- 1.1) and c-Myc (5.4 +/- 0.5 vs 12.5 +/- 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease. PMID- 27559734 TI - Plasticity and Adult Neurogenesis in Amphibians and Reptiles: More Questions than Answers. AB - Studies of the relationship between behavioral plasticity and new cells in the adult brain in amphibians and reptiles are sparse but demonstrate that environmental and hormonal variables do have an effect on the amount of cell proliferation and/or migration. The variables that are reviewed here are: enriched environment, social stimulation, spatial area use, season, photoperiod and temperature, and testosterone. Fewer data are available for amphibians than for reptiles, but for both groups many issues are still to be resolved. It is to be hoped that the questions raised here will generate more answers in future studies. PMID- 27559733 TI - Relative Handgrip Strength Is a Simple Indicator of Cardiometabolic Risk among Middle-Aged and Older People: A Nationwide Population-Based Study in Taiwan. AB - BACKGROUND: Muscle strength may play an important role in cardiovascular health. The study was intended to evaluate the association between cardiometabolic risk, risk of coronary artery disease and handgrip strength by using the relative handgrip strength. MATERIALS AND METHODS: Data of 927 Taiwanese aged 53 years and older (510 men and 417 women) were retrieved from a nationwide representative population-based cohort cross-sectional study in 2006. All participants were interviewed face-to-face and received measures of anthropometry, dominant handgrip strength, relative handgrip strength (summation of both handgrip strength divided by body mass index) and serum biomarkers. RESULTS: Multivariate linear regression analysis showed the significant association between relative handgrip strength and favorable cardiometabolic risk factors including blood pressure, triglyceride, total cholesterol to high density cholesterol(HDL-C) ratio, glycohemoglobin (HbA1c), uric acid, Framingham risk score in men, and HDL C, fasting glucose, HbA1c, log hsCRP in women. Dominant hand grip strength was only associated with log hsCRP in women. (p<0.05 for all), but was not significant associated with all cardiovascular biomarkers and FRS in both sex. CONCLUSIONS: Joint with handgrip strength and body size, as relative handgrip strength, may be a better tool to capture conceptual concomitant health, which may be a simple, inexpensive, and easy-to-use tool when targeting cardiovascular health in public health level. PMID- 27559735 TI - A Parallel Population Genomic and Hydrodynamic Approach to Fishery Management of Highly-Dispersive Marine Invertebrates: The Case of the Fijian Black-Lip Pearl Oyster Pinctada margaritifera. AB - Fishery management and conservation of marine species increasingly relies on genetic data to delineate biologically relevant stock boundaries. Unfortunately for high gene flow species which may display low, but statistically significant population structure, there is no clear consensus on the level of differentiation required to resolve distinct stocks. The use of fine-scale neutral and adaptive variation, considered together with environmental data can offer additional insights to this problem. Genome-wide genetic data (4,123 SNPs), together with an independent hydrodynamic particle dispersal model were used to inform farm and fishery management in the Fijian black-lip pearl oyster Pinctada margaritifera, where comprehensive fishery management is lacking, and the sustainability of exploitation uncertain. Weak fine-scale patterns of population structure were detected, indicative of broad-scale panmixia among wild oysters, while a hatchery sourced farmed population exhibited a higher degree of genetic divergence (Fst = 0.0850-0.102). This hatchery-produced population had also experienced a bottleneck (NeLD = 5.1; 95% C.I. = [5.1-5.3]); compared to infinite NeLD estimates for all wild oysters. Simulation of larval transport pathways confirmed the existence of broad-scale mixture by surface ocean currents, correlating well with fine-scale patterns of population structuring. Fst outlier tests failed to detect large numbers of loci supportive of selection, with 2-5 directional outlier SNPs identified (average Fst = 0.116). The lack of biologically significant population genetic structure, absence of evidence for local adaptation and larval dispersal simulation, all indicate the existence of a single genetic stock of P. margaritifera in the Fiji Islands. This approach using independent genomic and oceanographic tools has allowed fundamental insights into stock structure in this species, with transferability to other highly-dispersive marine taxa for their conservation and management. PMID- 27559736 TI - Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats. AB - BACKGROUND: Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results. METHODS: Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed. RESULTS: The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN. CONCLUSIONS: Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN. PMID- 27559737 TI - Reduced Maximal Force during Acute Anterior Knee Pain Is Associated with Deficits in Voluntary Muscle Activation. AB - Although maximal voluntary contraction (MVC) force is reduced during pain, studies using interpolated twitch show no consistent reduction of voluntary muscle drive. The present study aimed to test if the reduction in MVC force during acute experimental pain could be explained by increased activation of antagonist muscles, weak voluntary activation at baseline, or changes in force direction. Twenty-two healthy volunteers performed maximal voluntary isometric knee extensions before, during, and after the effects of hypertonic (pain) and isotonic (control) saline injections into the infrapatellar fat pad. The MVC force, voluntary activation, electromyographic (EMG) activity of agonist, antagonist, and auxiliary (hip) muscles, and pain cognition and anxiety scores were recorded. MVC force was 9.3% lower during pain than baseline (p < 0.001), but there was no systematic change in voluntary activation. Reduced MVC force during pain was variable between participants (SD: 14%), and was correlated with reduced voluntary activation (r = 0.90), baseline voluntary activation (r = - 0.62), and reduced EMG amplitude of agonist and antagonist muscles (all r > 0.52), but not with changes in force direction, pain or anxiety scores. Hence, reduced MVC force during acute pain was mainly explained by deficits in maximal voluntary drive. PMID- 27559738 TI - HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. AB - Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett's esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression. PMID- 27559739 TI - Correction: Rapid Diagnosis of Lung Tumors, a Feasability Study Using Maldi-Tof Mass Spectrometry. AB - [This corrects the article DOI: 10.1371/journal.pone.0155449.]. PMID- 27559740 TI - Correction: Replacing the Orchestra? - The Discernibility of Sample Library and Live Orchestra Sounds. AB - [This corrects the article DOI: 10.1371/journal.pone.0158324.]. PMID- 27559741 TI - Correction: Transcriptome Analysis Reveals Regulation of Gene Expression for Lipid Catabolism in Young Broilers by Butyrate Glycerides. AB - [This corrects the article DOI: 10.1371/journal.pone.0160751.]. PMID- 27559742 TI - Standing on the Shoulders of Giant Viruses: Five Lessons Learned about Large Viruses Infecting Small Eukaryotes and the Opportunities They Create. PMID- 27559743 TI - Amlexanox Blocks the Interaction between S100A4 and Epidermal Growth Factor and Inhibits Cell Proliferation. AB - The human S100A4 protein binds calcium, resulting in a change in its conformation to promote the interaction with its target protein. Human epidermal growth factor (EGF) is the target protein of S100A4 and a critical ligand of the receptor EGFR. The EGF/EGFR system promotes cell survival, differentiation, and growth by activating several signaling pathways. Amlexanox is an anti-inflammatory and anti allergic drug that is used to treat recurrent aphthous ulcers. In the present study, we determined that amlexanox interacts with S100A4 using heteronuclear single quantum correlation titration. We elucidated the interactions of S100A4 with EGF and amlexanox using fluorescence and nuclear magnetic resonance spectroscopy. We generated two binary models (for the S100A4-EGF and S100A4 amlexanox complexes) and observed that amlexanox and EGF share a similar binding region in mS100A4. We also used a WST-1 assay to investigate the bioactivity of S100A4, EGF, and amlexanox, and found that amlexanox blocks the binding between S100A4 and EGF, and is therefore useful for the development of new anti proliferation drugs. PMID- 27559745 TI - Multiple Cardiac Rhabdomyomas Visualised Using Micro-CT in a Case of Tuberous Sclerosis. AB - Cardiac rhabdomyoma is the most common tumour of the heart in infancy and childhood, representing approximately 60% of all primary cardiac tumours in these age groups. Though they have a tendency to regress with advancing age and are histologically benign, rhabdomyomas may cause mechanical obstruction to blood flow, arrhythmia, congestive cardiac failure and death and may be associated with underlying genetic syndromes such as tuberous sclerosis. We present the case of a primigravida in her early 20s with no significant medical history who was referred to the Fetal Medicine Unit at 34 weeks' gestation following the detection of an irregular fetal heartbeat. An anomaly scan at 20 weeks had been reported as normal. PMID- 27559746 TI - Real-Time Sexing of Chicken Embryos and Compatibility with in ovo Protocols. AB - The chicken embryo is an established model system for studying early vertebrate development. One of the major advantages of this model is the facility to perform manipulations in ovo and then continue incubation and observe the effects on embryonic development. However, in common with other vertebrate models, there is a tendency to disregard the sex of the experimental chicken embryos, and this can lead to erroneous conclusions, a lack of reproducibility, and wasted efforts. That this neglect is untenable is emphasised by the recent demonstration that avian cells and tissues have an inherent sex identity and that male and female tissues respond differently to the same stimulus. These sexually dimorphic characteristics dictate that analyses and manipulations involving chicken embryos should always be performed using tissues/embryos of known sex. Current sexing protocols are unsuitable in many instances because of the time constraints imposed by most in ovo procedures. To address this lack, we have developed a real time chicken sexing assay that is compatible with in ovo manipulations, reduces the number of embryos required, and conserves resources. PMID- 27559744 TI - Effectiveness of Non-Pharmacological Interventions to Prevent Falls in Older People: A Systematic Overview. The SENATOR Project ONTOP Series. AB - BACKGROUND: Falls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making. OBJECTIVES: To systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals. METHODS: We searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions. RESULTS: Fifty-nine systematic reviews were identified which consisted of single, multiple and multifactorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis. CONCLUSIONS: The aim of this overview of reviews of non-pharmacological interventions to prevent falls in older people in different settings, is to support clinicians and other healthcare workers with clinical decision-making by providing a comprehensive perspective of findings. PMID- 27559747 TI - The New USA NIH Strategic Plan for Complementary and Integrative Health: Interview with Josephine Briggs, MD. PMID- 27559748 TI - Hemispheric asymmetry in the hierarchical perception of music and speech. AB - The perception of music and speech involves a higher level, cognitive mechanism that allows listeners to form expectations for future music and speech events. This article comprehensively reviews studies on hemispheric differences in the formation of melodic and harmonic expectations in music and selectively reviews studies on hemispheric differences in the formation of syntactic and semantic expectations in speech. On the basis of this review, it is concluded that the higher level mechanism flexibly lateralizes music processing to either hemisphere depending on the expectation generated by a given musical context. When a context generates in the listener an expectation whose elements are sequentially ordered over time, higher level processing is dominant in the left hemisphere. When a context generates in the listener an expectation whose elements are not sequentially ordered over time, higher level processing is dominant in the right hemisphere. This article concludes with a spreading activation model that describes expectations for music and speech in terms of shared temporal and nontemporal representations. (PsycINFO Database Record PMID- 27559750 TI - In Situ Chemical Modification of Schottky Barrier in Solution-Processed Zinc Tin Oxide Diode. AB - Here we present a novel in situ chemical modification process to form vertical Schottky diodes using palladium (Pd) rectifying bottom contacts, amorphous zinc tin oxide (Zn-Sn-O) semiconductor made via acetate-based solution process, and molybdenum top ohmic contacts. Using X-ray photoelectron spectroscopy depth profiling, we show that oxygen plasma treatment of Pd creates a PdOx interface layer, which is then reduced back to metallic Pd by in situ reactions during Zn Sn-O film annealing. The plasma treatment ensures an oxygen-rich environment in the semiconductor near the Schottky barrier, reducing the level of oxygen deficiency-related defects and improving the rectifying contact. Using this process, we achieve diodes with high forward current density exceeding 10(3)A cm( 2) at 1 V, rectification ratios of >10(2), and ideality factors of around 1.9. The measured diode current-voltage characteristics are compared to numerical simulations of thermionic field emission with sub-bandgap states in the semiconductor, which we attribute to spatial variations in metal stoichiometry of amorphous Zn-Sn-O. To the best of our knowledge, this is the first demonstration of vertical Schottky diodes using solution-processed amorphous metal oxide semiconductor. Furthermore, the in situ chemical modification method developed here can be adapted to tune interface properties in many other oxide devices. PMID- 27559749 TI - Aqueous Suzuki Coupling Reactions of Basic Nitrogen-Containing Substrates in the Absence of Added Base and Ligand: Observation of High Yields under Acidic Conditions. AB - A series of aqueous heterogeneous Suzuki coupling reactions of substrates containing basic nitrogen centers with phenylboronic acid in the absence of added base and ligand is presented. High yields of products were obtained by employing aryl bromides containing aliphatic 1 degrees , 2 degrees , and 3 degrees amine substituents, and good to high yields were obtained by employing a variety of substituted bromopyridines. In the former series, the pH of the aqueous phase changed from basic to acidic during the course of the reaction, while in the latter series the aqueous phase was on the acidic side of the pH scale throughout the entire course of reaction. A mechanistic interpretation for these observations, which generally preserves the oxo palladium catalytic cycle widely accepted in the literature, is presented. PMID- 27559751 TI - Development of an Integrated Pipeline for Profiling Microbial Proteins from Mouse Fecal Samples by LC-MS/MS. AB - Metaproteomics is one approach to analyze the functional capacity of the gut microbiome but is limited by the ability to evenly extract proteins from diverse organisms within the gut. Herein, we have developed a pipeline to optimize sample preparation of stool obtained from germ-free (GF) mice that were gavaged a defined community of 11 bacterial strains isolated from the human gut. With 64% more proteins identified, bead-beating was confirmed to be an indispensable step for the extraction of bacterial proteins, especially for Gram-positive bacteria. Bacterial enrichment from mouse fecal samples was further optimized by evaluating three different methods: (1) a high-speed differential centrifugation (HCE) or (2) a low-speed differential centrifugation (LCE) and (3) a filter-aided method (FA). The HCE method was associated with dramatic loss of bacteria and 71% less recovery of bacterial proteins than the LCE method. Compared with LCE, the FA method also showed dramatic loss of the amount of bacteria recovered and decreased protein identifications from Gram-positive bacteria in the stool samples. Ultimately, LCE may provide an alternative and complementary method for enriching bacteria from small amounts of mouse fecal samples, which could aid in investigating bacterial function in health and disease. PMID- 27559752 TI - Controllable Preparation of Square Nickel Chalcogenide (NiS and NiSe2) Nanoplates for Superior Li/Na Ion Storage Properties. AB - A facile and bottom-up approach has been presented to prepare 2D Ni-MOFs based on cyanide-bridged hybrid coordination polymers. After thermally induced sulfurization and selenization processes, Ni-MOFs were successfully converted into NiS and NiSe2 nanoplates with carbon coating due to the decomposition of its organic parts. When evaluated as anodes of Li-ion batteries (LIBs) and Na-ion batteries (NIBs), NiS and NiSe2 nanoplates show high specific capacities, excellent rate capabilities, and stable cycling stability. The NiS plates show good Li storage properties, while NiSe2 plates show good Na storage properties as anode materials. The study of the diffusivity of Li(+) in NiS and Na(+) in NiSe2 shows consistent results with their Li/Na storage properties. The 2D MOFs-derived NiS and NiSe2 nanoplates reported in this work explore a new approach for the large-scale synthesis of 2D metal sulfides or selenides with potential applications for advanced energy storage. PMID- 27559754 TI - Assessing Drinking Water Quality and Water Safety Management in Sub-Saharan Africa Using Regulated Monitoring Data. AB - Universal access to safe drinking water is prioritized in the post-2015 Sustainable Development Goals. Collecting reliable and actionable water quality information in low-resource settings, however, is challenging, and little is known about the correspondence between water quality data collected by local monitoring agencies and global frameworks for water safety. Using 42 926 microbial water quality test results from 32 surveillance agencies and water suppliers in seven sub-Saharan African countries, we determined the degree to which water sources were monitored, how water quality varied by source type, and institutional responses to results. Sixty-four percent of the water samples were collected from piped supplies, although the majority of Africans rely on nonpiped sources. Piped supplies had the lowest levels of fecal indicator bacteria (FIB) compared to any other source type: only 4% of samples of water piped to plots and 2% of samples from water piped to public taps/standpipes were positive for FIB (n = 14 948 and n = 12 278, respectively). Among other types of improved sources, samples from harvested rainwater and boreholes were less often positive for FIB (22%, n = 167 and 31%, n = 3329, respectively) than protected springs or protected dug wells (39%, n = 472 and 65%, n = 505). When data from different settings were aggregated, the FIB levels in different source types broadly reflected the source-type water safety framework used by the Joint Monitoring Programme. However, the insufficient testing of nonpiped sources relative to their use indicates important gaps in current assessments. Our results emphasize the importance of local data collection for water safety management and measurement of progress toward universal safe drinking water access. PMID- 27559753 TI - Modeling and Analysis of Intercalant Effects on Circular DNA Conformation. AB - The large-scale conformation of DNA molecules plays a critical role in many basic elements of cellular functionality and viability. By targeting the structural properties of DNA, many cancer drugs, such as anthracyclines, effectively inhibit tumor growth but can also produce dangerous side effects. To enhance the development of innovative medications, rapid screening of structural changes to DNA can provide important insight into their mechanism of interaction. In this study, we report changes to circular DNA conformation from intercalation with ethidium bromide using all-atom molecular dynamics simulations and characterized experimentally by translocation through a silicon nitride solid-state nanopore. Our measurements reveal three distinct current blockade levels and a 6-fold increase in translocation times for ethidium bromide-treated circular DNA as compared to untreated circular DNA. We attribute these increases to changes in the supercoiled configuration hypothesized to be branched or looped structures formed in the circular DNA molecule. Further evidence of the conformational changes is demonstrated by qualitative atomic force microscopy analysis. These results expand the current methodology for predicting and characterizing DNA tertiary structure and advance nanopore technology as a platform for deciphering structural changes of other important biomolecules. PMID- 27559755 TI - Mechanosensing Controlled Directly by Tyrosine Kinases. AB - To understand how cells form tissues, we need to understand how the tyrosine kinases are involved in controlling cell mechanics, whether they act directly as parts of mechanosensing machines or indirectly. Cells test the critical parameter of matrix rigidity by locally contracting ("pinching") matrices and measuring forces, and the depletion of contractile units causes transformation. We report here that knocking down the receptor tyrosine kinases (RTKs), AXL, and ROR2, alters rigidity sensing and increases the magnitude or duration of local contraction events, respectively. Phospho-AXL and ROR2 localize to contraction units and bind major contractile components, tropomyosin 2.1 (AXL), myosin IIA (AXL), and filamin A (ROR2). At a molecular level, phosphorylated AXL localizes to active myosin filaments and phosphorylates tropomyosin at a tyrosine critical for adhesion formation. ROR2 binding of ligand is unnecessary, but binding filamin A helps function. Thus, AXL and ROR2 alter rigidity sensing and consequently morphogenic processes by directly controlling local mechanosensory contractions without ligands. PMID- 27559756 TI - Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates. AB - Nucleoside monophosphates and monophosphonates have been known for a long time to exert favorable pharmacological effects upon intracellular delivery. However, their development as drug molecules has been hindered by the inherent poor druglike properties of the monophosphate and monophosphonate groups. These include inefficient cellular uptake and poor in vivo stability, with this latter drawback being most relevant to monophosphates than monophosphonates. To address these limitations, numerous monophosphate and monophosphonate prodrug strategies have been developed and applied in the discovery of nucleoside monophosphate and monophosphonate prodrugs that can treat viral infections and cancer. The approval of sofosbuvir, a nucleoside monophosphate prodrug, highlighted the success to be had by employing these prodrug technologies in the discovery of nucleotide therapeutics. In this Miniperspective, we discuss the different key monophosphate and monophosphonate nucleoside prodrugs that entered clinical development, some of which may in the future be approved to treat various human diseases. PMID- 27559757 TI - Optimization of Protein Backbone Dihedral Angles by Means of Hamiltonian Reweighting. AB - Molecular dynamics simulations depend critically on the accuracy of the underlying force fields in properly representing biomolecules. Hence, it is crucial to validate the force-field parameter sets in this respect. In the context of the GROMOS force field, this is usually achieved by comparing simulation data to experimental observables for small molecules. In this study, we develop new amino acid backbone dihedral angle potential energy parameters based on the widely used 54A7 parameter set by matching to experimental J values and secondary structure propensity scales. In order to find the most appropriate backbone parameters, close to 100 000 different combinations of parameters have been screened. However, since the sheer number of combinations considered prohibits actual molecular dynamics simulations for each of them, we instead predicted the values for every combination using Hamiltonian reweighting. While the original 54A7 parameter set fails to reproduce the experimental data, we are able to provide parameters that match significantly better. However, to ensure applicability in the context of larger peptides and full proteins, further studies have to be undertaken. PMID- 27559758 TI - Correction to "Effects of Molecular Symmetry on the Electronic Transitions in Carotenoids". PMID- 27559759 TI - Vital Signs: Epidemiology of Sepsis: Prevalence of Health Care Factors and Opportunities for Prevention. AB - BACKGROUND: Sepsis is a serious and often fatal clinical syndrome, resulting from infection. Information on patient demographics, risk factors, and infections leading to sepsis is needed to integrate comprehensive sepsis prevention, early recognition, and treatment strategies. METHODS: To describe characteristics of patients with sepsis, CDC and partners conducted a retrospective chart review in four New York hospitals. Random samples of medical records from adult and pediatric patients with administrative codes for severe sepsis or septic shock were reviewed. RESULTS: Medical records of 246 adults and 79 children (aged birth to 17 years) were reviewed. Overall, 72% of patients had a health care factor during the 30 days before sepsis admission or a selected chronic condition likely to require frequent medical care. Pneumonia was the most common infection leading to sepsis. The most common pathogens isolated from blood cultures were Escherichia coli in adults aged >=18 years, Klebsiella spp. in children aged >=1 year, and Enterococcus spp. in infants aged <1 year; for 106 (33%) patients, no pathogen was isolated. Eighty-two (25%) patients with sepsis died, including 65 (26%) adults and 17 (22%) infants and children. CONCLUSIONS: Infection prevention strategies (e.g., vaccination, reducing transmission of pathogens in health care environments, and appropriate management of chronic diseases) are likely to have a substantial impact on reducing sepsis. CDC, in partnership with organizations representing clinicians, patients, and other stakeholders, is launching a comprehensive campaign to demonstrate that prevention of infections that cause sepsis, and early recognition of sepsis, are integral to overall patient safety. PMID- 27559760 TI - Rigid Rod-Based FRET Probes for Membrane Sensing Applications. AB - Oligospirothioketal (OSTK) rods are presented as an adjustable scaffold for optical membrane probes. The OSTK rods are readily incorporated into lipid bilayers due to their hydrophobic backbones. Because of their high length-over diameter aspect ratio, only a minimal disturbance of the lipid bilayer is caused. OSTK rods show outstanding rigidity and allow defined labeling with fluorescent dyes, yielding full control of the orientation between the dye and OSTK skeleton. This allows the construction of novel Forster resonance energy transfer probes with highly defined relative orientations of the transition dipole moments of the donor and acceptor dyes and makes the class of OSTK probes a powerful, flexible toolbox for optical biosensing applications. Data on steady-state and time resolved fluorescence experiments investigating the incorporation of coumarin- and [1,3]dioxolo[4,5-f][1,3]benzo-dioxole-labeled OSTKs in large unilamellar vesicles are presented as a show case. PMID- 27559762 TI - The 1st World Association for Infectious Diseases and Immunological Disorders (WAidid) Congress, Milan, Italy. PMID- 27559761 TI - Prevalence of gyrA Mutations in Nalidixic Acid-Resistant Strains of Salmonella Enteritidis Isolated from Humans, Food, Chickens, and the Farm Environment in Brazil. AB - Salmonella Enteritidis strains that are resistant to nalidixic acid and exhibit reduced susceptibility to fluoroquinolones have been increasing worldwide. In Brazil, few studies have been conducted to elucidate the quinolone resistance mechanisms of S. Enteritidis strains. This study analyzed the profile of gyrA, gyrB, parC, and parE mutations and plasmid-mediated quinolone resistance (PMQR) mechanisms in S. Enteritidis NalR strains isolated in Brazil. Moreover, the minimum inhibitory concentrations (MICs) of ciprofloxacin were evaluated in 84 NalR strains and compared with 20 NalS strains. The mutation profiles of the gyrA gene were accessed by high-resolution melting analysis and gyrB, parC, and parE by quinolone resistance-determining region sequencing. The MICs of ciprofloxacin were accessed with Etest(r). The strains were divided into five gyrA melting profiles. The NalR strains exhibited the following amino acid substitutions: Ser97->Pro, Ser83->Phe, Asp87->Asn, or Asp87->Tyr. The average MICs of ciprofloxacin was 0.006 MUg/ml in the NalS and 0.09 MUg/ml in the NalR strains. No points of mutation were observed in the genes gyrB, parC, and parE. The qnrB gene was found in two strains. In conclusion, the reduced susceptibility to ciprofloxacin observed in NalR strains may cause treatment failures once this drug is commonly used to treat Salmonella infections. Moreover, this reduced susceptibility in these Brazilian strains was provided by target alteration of gene gyrA and not by mobile elements, such as resistance plasmids. PMID- 27559763 TI - A qualitative study of patient experiences of decentralized acute healthcare services. AB - OBJECTIVE: Municipality acute wards (MAWs) have recently been launched in Norway as an alternative to hospitalizations, and are aimed at providing treatment for patients who otherwise would have been hospitalized. The objective of this study was to explore how patients normally admitted to hospitals perceived the quality and safety of treatment in MAWs. DESIGN: The study had a qualitative design. Thematic analysis was used to analyze the data. SETTING: The study was conducted in a county in south-eastern Norway and included five different MAWs. PATIENTS: Semi-structured interviews were conducted with 27 participants who had required acute health care and who had been discharged from the five MAWs. RESULTS: Three subthemes were identified that related to the overarching theme of hospital-like standards ("almost a hospital, but..."), namely (a) treatment and competence, (b) location and physical environment, and (c) adequate time for care. Participants reported the treatment to be comparable to hospital care, but they also experienced limitations. Participants spoke positively about MAW personnel and the advantages of having a single patient room, a calm environment, and proximity to home. CONCLUSIONS: Participants felt safe when treated at MAWs, even though they realized that the diagnostic services were not similar to that in hospitals. Geographical proximity, treatment facilities and time for care positively distinguished MAWs from hospitals, while the lack of diagnostic resources was stressed as a limitation. Key points Municipality acute wards (MAWs) have been implemented across Norway. Research on patient perspectives on the decentralization of acute healthcare in MAWs is lacking. * Patients perceive decentralized acute healthcare and treatment as being comparable to the quality they would have expected in hospitals. * Geographical proximity, a home-like atmosphere and time for care were aspects stressed as positive features of the decentralized services. * Lack of diagnostic resources was seen as a limitation. PMID- 27559765 TI - Charge heterogeneity: Basic antibody charge variants with increased binding to Fc receptors. AB - We identified active isoforms of the chimeric anti-GD2 antibody, ch14.18, a recombinant antibody produced in Chinese hamster ovary cells, which is already used in clinical trials. 1,2,3 We separated the antibody by high resolution ion exchange chromatography with linear pH gradient elution into acidic, main and basic charge variants on a preparative scale yielding enough material for an in depth study of the sources and the effects of microheterogeneity. The binding affinity of the charge variants toward the antigen and various cell surface receptors was studied by Biacore. Effector functions were evaluated using cellular assays for antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity. Basic charge variants showed increased binding to cell surface receptor FcgammaRIIIa, which plays a major role in regulating effector functions. Furthermore, increased binding of the basic fractions to the neonatal receptor was observed. As this receptor mediates the prolonged half-life of IgG in human serum, this data may well hint at an increased serum half-life of these basic variants compared to their more acidic counterparts. Different glycoform patterns, C-terminal lysine clipping and N-terminal pyroglutamate formation were identified as the main structural sources for the observed isoform pattern. Potential differences in structural stability between individual charge variant fractions by nano differential scanning calorimetry could not been detected. Our in-vitro data suggests that the connection between microheterogeneity and the biological activity of recombinant antibody therapeutics deserves more attention than commonly accepted. PMID- 27559767 TI - Aurora B twists on histones for activation. PMID- 27559766 TI - Network meta-analysis of balloon angioplasty, nondrug metal stent, drug-eluting balloon, and drug-eluting stent for treatment of infrapopliteal artery occlusive disease. AB - PURPOSE: We aimed to conduct a network meta-analysis of mixed treatments for the infrapopliteal artery occlusive disease. METHODS: We searched randomized controlled trials (RCTs) regarding balloon angioplasty (BA), nondrug metal stent (NDMS), drug-eluting balloon (DEB), or drug-eluting stent (DES) in PubMed, Embase, CENTRAL, Ovid, Sinomed, and other relevant websites. We selected and assessed the trials that met the inclusion criteria and conducted a network meta analysis using the ADDIS software. RESULTS: We included 11 relevant trials. We analyzed data of 1322 patients with infrapopliteal artery occlusive disease, of which 351 were in the NDMS vs. DES trials, 231 in the NDMS vs. BA trials, 490 in the BA vs. DEB trials, 50 in the DEB vs. DES trials, and 200 in the BA vs. DES trials. The network meta-analysis indicated that with NDMS as the reference, DES had a better result with respect to restenosis (odds ratio [OR], 5.16; 95% credible interval [CI], 1.58-18.41; probability of the best treatment, 84%) and amputation (OR, 2.50; 95% CI, 0.81-7.11; probability of the best treatment, 61%) and DEB had a better result with respect to target lesion revascularization (TLR; OR, 3.74; 95% CI, 0.78-17.05; probability of the best treatment, 57%). Moreover, with BA as the reference, NDMS had a better result with respect to technical success (OR, 0.10; 95% CI, 0.00-1.15; probability of the best treatment, 86%). CONCLUSION: Our meta-analysis revealed that DES is a better treatment with respect to short-term patency and limb salvage rate, NMDS may provide a better technical success, and DEB and DES are good choices for reducing revascularization. PMID- 27559768 TI - A Survey of Perinatal Palliative Care Programs in the United States: Structure, Processes, and Outcomes. AB - BACKGROUND: Perinatal palliative care (PPC) programs are proliferating nationwide, but little is known about their structure, process, or desired outcomes, to inform future program development. OBJECTIVE: To explicate structure, processes, and outcomes of PPC programs, specifically how they coordinate care and manage goals of care meetings, as well as providers' perceptions of the most beneficial components of care and their expected care outcomes. DESIGN: Free-text response data were taken from a 48-item online survey organized around the eight domains defined by the National Consensus Project for Quality Palliative Care (NCP). Responses related to NCP Domain 1 (Structure and Process of Care) were analyzed using conventional content analysis. SUBJECTS: U.S. PPC program representatives (N = 75) from 30 states. RESULTS: The majority of programs have a care coordinator, but roles vary from direct patient care to program administration. Participants described a range of topics discussed during family meetings to determine parental goals across the perinatal period. Support and respect for parent preferences and choices were the most important components of care. Desired program outcomes include parental satisfaction with physical and psychosocial support, help with the decision-making process, opportunity to parent their infant, infant comfort, and positive personal and family growth. CONCLUSIONS: While PPC programs do not often measure quality, their goals are family centered, with a focus on parent satisfaction with decision making and psychosocial support. PPC programs coordinate interdisciplinary care by arranging meetings and advocating for families. More research is needed to understand parent perspectives on care provided. PMID- 27559769 TI - Regional Disparities in China in the Prevalence of Children Who Are Obese or Overweight. AB - China has experienced rapid socioeconomic transitions during the last three decades, which may result in a rising prevalence of overweight and obese children in China. This article aims to fill in the existing knowledge gap by an analysis of the China Health and Nutrition Survey data to study the national prevalence of children who are overweight and obese as well as how the regional disparities and age differences in prevalence have changed between 1989 and 2009. PMID- 27559770 TI - Goat horn-induced intracranial emphysema and orbital injury. AB - This is a case description of a male patient found to have orbital and intracranial emphysema, specifically with air in his cavernous sinuses bilaterally following penetrating trauma to the medial orbit from a goat's horn. There were no orbital or skull base fractures. Although the presence of traumatic intracranial emphysema is not uncommon, it is typically the result of direct communication of the cranial vault with the paranasal sinuses in the setting of associated fracture or, alternatively, from direct penetration and inoculation. We present a rare case of orbital emphysema with traumatic intracranial emphysema without these previously described associations and postulate a mech''anism behind its development. PMID- 27559816 TI - Hospitalization expenses of acute ischemic stroke patients with atrial fibrillation relative to those with normal sinus rhythm. AB - BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is a risk factor for acute ischemic stroke (AIS). In mainland China, little is known of the hospitalization expenses of AIS patients with AF compared to those with normal sinus rhythm (SR). This study compared the itemized expenses of AIS patients with or without AF in a hospital in Huizhou City. METHODS: Patients hospitalized for AIS from March 2014 to March 2015 were enrolled, including 73 with AF and 751 with normal SR. Stroke severity was scored using the National Institutes of Health Stroke Scale (NIHSS). Non-parametric statistical tests were used to determine differences in hospital expenses between the two groups, of which influencing factors were analyzed using single factor and multiple stepwise linear regression analyses. RESULTS: Medicine was the predominant expense during hospitalization of all AIS patients. Patients with AF incurred significantly higher expenses for medicine, bed, treatments, examinations, laboratory tests, and nursing than patients with normal SR (p < .05); however, the medicine and bed expenses of patients at the same stroke level in the two groups were similar. Independent factors influencing the higher costs of AF patients were hospital length of stay, pulmonary infection, urinary-tract infection, NIHSS scoring, gastrointestinal bleeding, and congestive heart failure (p < .05). Independent predictors of hospital length of stay were NIHSS scoring, pulmonary infection, and urinary-tract infection (p < .05). CONCLUSION: AIS patients with AF incurred higher expenses during hospitalization compared with those with normal SR, due to greater stroke severity, higher rates of pulmonary infection and congestive heart failure, and longer hospital stays. PMID- 27559817 TI - Skin friction related behaviour of artificial turf systems. AB - The occurrence of skin friction related injuries is an issue for artificial turf sports pitches and remains a barrier to their acceptance. The purpose of this study was to evaluate the current industry standard Securisport(r) Sports Surface Tester that measures skin surface related frictional behaviour of artificial turf. Little research has been published about the device and its efficacy, despite its widespread use as a standard FIFA test instrument. To achieve a range of frictional behaviours, several "third generation" (3G) carpet and infill combinations were investigated; friction time profiles throughout the Securisport rotations were assessed in combination with independent measurements of skin roughness before and after friction testing via 3D surface scanning. The results indicated that carpets without infill had greatest friction (coefficients of friction 0.97-1.20) while those completely filled with sand or rubber had similar and lower values independent of carpet type (coefficient of friction (COF) ~0.57). Surface roughness of a silicone skin (s-skin) decreased after friction testing, with the largest change on sand infilled surfaces, indicating an "abrasive" polishing effect. The combined data show that the s-skin is damaged in a surface-specific manner, thus the Securisport COF values appear to be a poor measure of the potential for skin abrasion. It is proposed that the change in s skin roughness improves assessment of the potential for skin damage when players slide on artificial turf. PMID- 27559818 TI - Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. AB - RATIONALE: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited. OBJECTIVES: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects. METHODS: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation. MEASUREMENTS AND MAIN RESULTS: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain-consequent to increased chemosensitivity and delay-the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = -0.68) oscillations (P < 0.001 for all, both groups combined). CONCLUSIONS: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population. PMID- 27559819 TI - Change the things you can: Emotion regulation is more beneficial for people from lower than from higher socioeconomic status. AB - Emotion regulation is central to psychological health, and several emotion regulation strategies have been identified as beneficial. However, new theorizing suggests the benefits of emotion regulation should depend on its context. One important contextual moderator might be socioeconomic status (SES), because SES powerfully shapes people's ecology: lower SES affords less control over one's environment and thus, the ability to self-regulate should be particularly important. Accordingly, effectively regulating one's emotions (e.g., using cognitive reappraisal) could be more beneficial in lower (vs. higher) SES contexts. Three studies (N = 429) tested whether SES moderates the link between cognitive reappraisal ability (CRA; measured with surveys and in the laboratory) and depression. Each study and a meta-analysis of the 3 studies revealed that CRA was associated with less depression for lower SES but not higher SES individuals. Thus, CRA may be uniquely beneficial in lower SES contexts. More broadly, the effects of emotion regulation depend upon the ecology within which it is used. (PsycINFO Database Record PMID- 27559820 TI - Now you have my attention: Empathic accuracy pathways in couples and the role of conflict. AB - Recent research on empathy finds evidence for 2 different pathways that enable individuals to accurately infer other persons' inner mental states: an automatic, indirect pathway that operates by having a mental state similar to the target's and (correctly) assuming that this state is similar to the target's, and a more controlled direct pathway that involves assessing the target's mental state with no regard for one's own. We present 3 daily diary studies (N = 53, 38 and 80 couples) examining the contribution of these pathways to empathic accuracy in daily assessments of romantic partners' negative moods, and examine the effects of gender and relational conflict on these pathways. Our studies revealed that both pathways consistently contributed to accuracy. Additionally, partners demonstrated greater indirect accuracy on conflict (vs. nonconflict) days, and indirect accuracy was somewhat higher for women than for men on conflict days (with the opposite pattern on nonconflict days). More importantly, we found evidence for a novel third pathway, in which the perception of conflict itself led to (correct) higher estimation of negative affect and thus, to higher accuracy. This pathway figured more consistently for men than for women. In our discussion, we link the pathways obtained in these studies to the extant social neuroscientific literature on empathy systems, arguing that the indirect pathway involves the effects of experience sharing, while the direct and conflict-based pathways involve the mental state attributions (Zaki & Ochsner, 2011). These findings demonstrate the importance of examining various empathic pathways for the understanding of empathic processes. (PsycINFO Database Record PMID- 27559821 TI - Context shapes social judgments of positive emotion suppression and expression. AB - It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record PMID- 27559822 TI - Regioselective Iodine-Catalyzed Construction of Polysubstituted Pyrroles from Allenes and Enamines. AB - A novel I2-catalyzed tandem Michael addition/oxidative annulation of allenes and enamines for the construction of polysubstituted pyrroles has been developed. This protocol represents an efficient and highly regioselective way to access functionalized pyrroles in moderate to excellent yields under mild conditions. PMID- 27559823 TI - Self-Healing Polymer Dielectric for a High Capacitance Gate Insulator. AB - Self-healing materials are required for development of various flexible electronic devices to repair cracks and ruptures caused by repetitive bending or folding. Specifically, a self-healing dielectric layer has huge potential to achieve healing electronics without mechanical breakdown in flexible operations. Here, we developed a high performance self-healing dielectric layer with an ionic liquid and catechol-functionalized polymer which exhibited a self-healing ability for both bulk and film states under mild self-healing conditions at 55 degrees C for 30 min. Due to the sufficient ion mobility of the ionic liquid in the polymer matrix, it had a high capacitance value above 1 MUF/cm(2) at 20 Hz. Moreover, zinc oxide (ZnO) thin-film transistors (TFTs) with a self-healing dielectric layer exhibited a high field-effect mobility of 16.1 +/- 3.07 cm(2) V(-1) s(-1) at a gate bias of 3 V. Even after repetitive self-healing of the dielectric layer from mechanical breaking, the electrical performance of the TFTs was well maintained. PMID- 27559825 TI - Effects of Substitutional Dopants on the Photoresponse of a Polyoxotitanate Cluster. AB - In this paper, using a simple method, 17 isostructural polyoxotitanates (POTs) were synthesized, including the pristine [Ti12O16(O(i)Pr)16], the monodefected [Ti11O13(O(i)Pr)18], and the heterometal-doped [Ti11O14(O(i)Pr)17(ML)] (M = Mg, Ca, Zn, Cd, Co, or Ni; L = Cl, Br, I, or NO3). The electronic structures of these POTs were determined by UV-vis spectroscopy and DFT calculations. Upon UV irradiation of the POTs, electron spin resonance showed the formation of Ti(III) under anaerobic conditions and superoxide (O2(*-)) in the presence of O2. The photoactivities of the POTs were then probed with Ti(III) production and short circuit photocurrent experiments. The photophysical processes were studied using steady-state and transient photoluminescence. The results show that within the very similar structures, the deexcitation processes of the photoexcited POTs can be greatly affected by the dopants, which result in enhanced or decreased photoactivities. Co and Ni doping enhances the absorption of the visible light accompanied by serious loss of UV photoactivities. On the other hand, a Ti vacancy (in [Ti11O13(O(i)Pr)18]) does not reduce the band gap of a POT but improves the UV photoactivities by serving as surface reaction site. The POTs were then used as molecular models of titanium oxide nanoparticles to understand some important issues relevant to doped titanate, i.e., coordination environment of the dopant metal, electronic structure, photoactivities, and photophysical processes. Our present findings suggest that for solar energy harvesting applications of titanium oxides like photocatalysis and solar cells substitution of titanium atoms by transition metal ions (like Co and Ni) to extend the absorption edges may not be an efficient way, while loading of Ti vacancies is very effective. PMID- 27559824 TI - Human Lin28 Forms a High-Affinity 1:1 Complex with the 106~363 Cluster miRNA miR 363. AB - Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein-RNA complex are unknown. Characterization of human Lin28's interaction with RNA has been complicated by difficulties in producing stable RNA free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54.1 +/- 4.2 nM, in agreement with previous data on a murine homologue. We show that human Lin28A binds miR-363 with a 1:1 stoichiometry and with a similar, if not higher, affinity (Kd = 16.6 +/- 1.9 nM). Further analysis suggests that the interaction of the N-terminal cold shock domain of Lin28A with RNA is salt-dependent, supporting a model in which the cold shock domain allows the protein to sample RNA substrates through transient electrostatic interactions. PMID- 27559826 TI - Design of Perovskite Oxides as Anion-Intercalation-Type Electrodes for Supercapacitors: Cation Leaching Effect. AB - Oxygen ions can be exploited as a charge carrier to effectively realize a new type of anion-intercalation supercapacitor. In this study, to get some useful guidelines for future materials development, we comparatively studied SrCoO3 delta (SC), Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF), and Co3O4 as electrodes in supercapacitors with aqueous alkaline electrolyte. The effect of interaction between the electrode materials with the alkaline solution was focused on the structure and specific surface area of the electrode material, and ultimately the electrochemical performance was emphasized. Both BSCF and SC were found to experience cation leaching in alkaline solution, resulting in an increase in the specific surface area of the material, but overleaching caused the damage of perovskite structure of BSCF. Barium leaching was more serious than strontium, and the cation leaching was component dependent. Although high initial capacitance was achieved for BSCF, it was not a good candidate as intercalation type electrode for supercapacitor because of poor cycling stability from serious Ba(2+) and Sr(2+) leaching. Instead, SC was a favorable electrode candidate for practical use in supercapacitors due to its high capacity and proper cation leaching capacity, which brought beneficial effect on cycling stability. It is suggested that cation leaching effect should be seriously considered in the development of new perovskite materials as electrodes for supercapacitors. PMID- 27559827 TI - A novel 1,3,5-triaminocyclohexane-based tripodal ligand forms a unique tetra(pyrazolate)-bridged tricopper(ii) core: solution equilibrium, structure and catecholase activity. AB - Copper(ii) complexes of a polydentate tripodal ligand L * 3HCl (L = N,N',N'' tris(5-pyrazolylmethyl)-cis,cis-1,3,5-triaminocyclohexane) were characterized in both solution and solid states. Combined evaluation of potentiometric, UV-VIS, and EPR data indicated the formation of two mononuclear (CuHL, CuL) and three trinuclear (Cu3H-xL2, x = 2, 3, 4) complexes. The high stability and spectroscopic properties of the CuL species indicate a coordination of two pyrazole rings in addition to the three secondary amino groups of L in a square pyramidal geometry. In parallel with the formation of trinuclear species, intense charge transfer bands appear at around 400-500 nm, which indicate the formation of pyrazolate-bridged complexes. The crystal structure of [Cu3H-4L2](ClO4)2.5H2O (1) reveals the formation of a unique trinuclear complex that features a tetra(pyrazolate)-bridged linear tricopper(ii) core. The CuCu interatomic distances are around 3.8 A. The two peripheral copper(ii) ions have a slightly distorted square pyramidal geometry. The four pyrazole rings bound to the peripheral copper(ii) ions are deprotonated and create a flattened tetrahedral environment for the central copper(ii), i.e. the formation of the trinuclear complexes is under the allosteric control of the two peripheral copper(ii) ions. The triply deprotonated trinuclear complex is an efficient catechol oxidase mimic with a surprisingly low pH optimum at pH = 5.6. Since the mononuclear CuL species is not able to promote the oxidation of 3,5-di-tert-butylcatechol, we assume that the central copper(ii) ion of the trinuclear complex with an unsaturated coordination sphere has a fundamental role in the binding and oxidation of the substrate. The experimental and structural details were further elaborated by a series of hybrid density functional theory calculations that support the presence of an antiferromagnetically coupled ground state. However, the magnitude and the pattern of spin coupling are dependent on the composition of the functionals. The optimized theoretical structures highlight the role of the crystal packing effects in inducing asymmetry between the two peripheral copper(ii) sites. PMID- 27559828 TI - Dual Kinase-Bromodomain Inhibitors in Anticancer Drug Discovery: A Structural and Pharmacological Perspective. AB - Protein kinases play crucial roles in several cell transformation processes and are validated drug targets for many human diseases, including cancer. Nevertheless, most tumors have eluded the effects of inhibition of a single kinase by activating resistance mechanisms and/or alternative pathways and escape mechanisms. In recent years, multitarget approaches directed toward inhibition of kinases and targets of different families have received increasing attention. In particular, co-targeting kinases and bromodomain epigenetic reader proteins has rapidly emerged as a promising approach to cancer drug development. In this manuscript, we will review the recent discoveries that led to the identification and optimization of dual kinase/bromodomain inhibitors. We will analyze and compare the structural features required for dual inhibition and comment on the potential of this approach in anticancer drug discovery. Moreover, we will introduce computational approaches useful for the identification of dual kinase/bromodomain inhibitors and generate ad hoc pharmacophore and docking models. PMID- 27559829 TI - Nanoparticle "switch-on" by tetrazine triggering. AB - This work describes how a small-molecule chemical trigger, reacting through the mediatory of an inverse electron demand Diels-Alder reaction, results in enhanced cellular uptake and selective nanoparticle disintegration and cargo liberation, via gross polymeric morphological alterations. The power of these responsive nanoparticles is demonstrated through encapsulation of the anti-cancer agent doxorubicin and its triggered release, allowing controlled cell death in response to a small-molecule chemical trigger. PMID- 27559831 TI - Prediction of Protein Pairs Sharing Common Active Ligands Using Protein Sequence, Structure, and Ligand Similarity. AB - We benchmarked the ability of comparative computational approaches to correctly discriminate protein pairs sharing a common active ligand (positive protein pairs) from protein pairs with no common active ligands (negative protein pairs). Since the target and the off-targets of a drug share at least a common ligand, i.e., the drug itself, the prediction of positive protein pairs may help identify off-targets. We evaluated representative protein-centric and ligand-centric approaches, including (1) 2D and 3D ligand similarity, (2) several measures of protein sequence similarity in conjunction with different sequence sources (e.g., full protein sequence versus binding site residues), and (3) a newly described pocket shape similarity and alignment program called SiteHopper. While the sequence-based alignment of pocket residues achieved the best overall performance, SiteHopper outperformed sequence-based approaches for unrelated proteins with only 20-30% pocket residue identity. Analogously, among ligand centric approaches, path-based fingerprints achieved the best overall performance, but ROCS-based ligand shape similarity outperformed path-based fingerprints for structurally dissimilar ligands (Tanimoto 25%-40%). A significant drop in recognition performance was observed for ligand-centric approaches when PDB ligands were used instead of ChEMBL ligands. Finally, we analyzed the relationship between pocket shape and ligand shape in our data set and found that similar ligands tend to bind to similar pockets while similar pockets may accept a range of different-shaped ligands. PMID- 27559830 TI - Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection - United States, August 2016. AB - CDC has updated its interim guidance for U.S. health care providers caring for infants born to mothers with possible Zika virus infection during pregnancy (1). Laboratory testing is recommended for 1) infants born to mothers with laboratory evidence of Zika virus infection during pregnancy and 2) infants who have abnormal clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission, regardless of maternal Zika virus test results. Congenital Zika syndrome is a recently recognized pattern of congenital anomalies associated with Zika virus infection during pregnancy that includes microcephaly, intracranial calcifications or other brain anomalies, or eye anomalies, among others (2). Recommended infant laboratory evaluation includes both molecular (real-time reverse transcription polymerase chain reaction [rRT-PCR]) and serologic (immunoglobulin M [IgM]) testing. Initial samples should be collected directly from the infant in the first 2 days of life, if possible; testing of cord blood is not recommended. A positive infant serum or urine rRT-PCR test result confirms congenital Zika virus infection. Positive Zika virus IgM testing, with a negative rRT-PCR result, indicates probable congenital Zika virus infection. In addition to infant Zika virus testing, initial evaluation of all infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should include a comprehensive physical examination, including a neurologic examination, postnatal head ultrasound, and standard newborn hearing screen. Infants with laboratory evidence of congenital Zika virus infection should have a comprehensive ophthalmologic exam and hearing assessment by auditory brainstem response (ABR) testing before 1 month of age. Recommendations for follow-up of infants with laboratory evidence of congenital Zika virus infection depend on whether abnormalities consistent with congenital Zika syndrome are present. Infants with abnormalities consistent with congenital Zika syndrome should have a coordinated evaluation by multiple specialists within the first month of life; additional evaluations will be needed within the first year of life, including assessments of vision, hearing, feeding, growth, and neurodevelopmental and endocrine function. Families and caregivers will also need ongoing psychosocial support and assistance with coordination of care. Infants with laboratory evidence of congenital Zika virus infection without apparent abnormalities should have ongoing developmental monitoring and screening by the primary care provider; repeat hearing testing is recommended. This guidance will be updated when additional information becomes available. PMID- 27559832 TI - Interaction of a Julolidine-Based Neutral Ultrafast Molecular Rotor with Natural DNA: Spectroscopic and Molecular Docking Studies. AB - Ultrafast molecular rotors (UMRs) are reported to be one of the best fluorescent sensors to study different microenvironments, including biomolecules. In the present work, we have explored the possibility of application of a julolidine based neutral UMR, 9-(2,2-dicyano vinyl) julolidine (DCVJ), as a DNA sensor and studied its mode of binding with DNA in detail using spectroscopic and molecular docking techniques. Our spectroscopic studies indicate that association of DCVJ with DNA leads to a very large enhancement in its emission intensity. Detailed investigation reveals that, despite being a neutral molecule, binding of DCVJ with DNA is largely modulated in the presence of salt. Such an unusual salt effect has been explained by invoking the ion-dipole interaction between DCVJ and the phosphate backbone of DNA. The ion-dipole interaction has also been established by studying the interaction of DCVJ with nucleosides. Detailed time resolved studies show that the twisting motion around the vinyl bond in DCVJ gets retarded to a great extent because of its association with DNA molecules. Through competitive binding studies, it has also been established that DCVJ also binds to DNA through intercalation. Finally, quantum chemical calculations and molecular docking studies have been performed to confirm the mode of binding of DCVJ with DNA. PMID- 27559833 TI - Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease. AB - Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement. PMID- 27559834 TI - Promoting experimental rigor in the conduct of conditioned pain modulation studies: the importance of reliability. PMID- 27559835 TI - Reliability of conditioned pain modulation: a systematic review. AB - A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational studies of the repeatability of a CPM test paradigm in adult humans were included. Two independent reviewers assessed the risk of bias in 6 domains; study participation; study attrition; prognostic factor measurement; outcome measurement; confounding and analysis using the Quality in Prognosis Studies (QUIPS) critical assessment tool. Intraclass correlation coefficients (ICCs) less than 0.4 were considered to be poor; 0.4 and 0.59 to be fair; 0.6 and 0.75 good and greater than 0.75 excellent. Ten studies were included in the final review. Meta-analysis was not appropriate because of differences between studies. The intersession reliability of the CPM effect was investigated in 8 studies and reported as good (ICC = 0.6-0.75) in 3 studies and excellent (ICC > 0.75) in subgroups in 2 of those 3. The assessment of risk of bias demonstrated that reporting is not comprehensive for the description of sample demographics, recruitment strategy, and study attrition. The absence of blinding, a lack of control for confounding factors, and lack of standardisation in statistical analysis are common. Conditioned pain modulation is a reliable measure; however, the degree of reliability is heavily dependent on stimulation parameters and study methodology and this warrants consideration for investigators. The validation of CPM as a robust prognostic factor in experimental and clinical pain studies may be facilitated by improvements in the reporting of CPM reliability studies. PMID- 27559836 TI - Comprehensive systematic review of long-term opioids in women with chronic noncancer pain and associated reproductive dysfunction (hypothalamic-pituitary gonadal axis disruption). AB - A comprehensive systematic literature review of reproductive side effects in women aged 18 to 55 years treated with opioids for 1 month or longer for chronic noncancer pain. A search of 7 databases including EMBASE and Medline was undertaken (October 2014 and a limited rerun April 2016). The search contained key words for opioids (generic and specific drug names) and side effects (generic and specific reproductive). Titles were screened using predefined criteria by a single reviewer and abstracts and full texts by 2 independent reviewers. A total of 10,684 articles were identified and 12 full texts (cohort [n = 1], case control [n = 4], cross-sectional [n = 4], case series [n = 1], and case report [n = 2] with a maximum of 41 cases in 1 article) were included covering 3 different modes of administration: oral (n = 6), intrathecal (n = 5), and transdermal (n = 1). Amenorrhoea occurred in 23% to 71% of those receiving oral or intrathecal opioids. Decreased libido was seen in 61% to 100%. Of the 10 studies that undertook hormonal assays, only 2 studies showed a statistically significant decrease in hormone levels. This review supports the view that there is a potential relationship between the use of long-term opioids in women and reproductive side effects. The evidence is however weak and the mode of administration, duration, type, and dose of opioid might influence associations. Although hormone levels were statistically significant in only 2 studies, women exhibited clinically important symptoms (decreased libido and altered menstrual cycle). Further investigation is required with larger cohorts and analysis of different delivery methods. PMID- 27559837 TI - DNA self-assembly-driven positioning of molecular components on nanopatterned surfaces. AB - We present a method for the specific, spatially targeted attachment of DNA molecules to lithographically patterned gold surfaces-demonstrated by bridging DNA strands across nanogap electrode structures. An alkanethiol self-assembled monolayer was employed as a molecular resist, which could be selectively removed via electrochemical desorption, allowing the binding of thiolated DNA anchoring oligonucleotides to each electrode. After introducing a bridging DNA molecule with single-stranded ends complementary to the electrode-tethered anchoring oligonucleotides, the positioning of the DNA molecule across the electrode gap, driven by self-assembly, occurred autonomously. This demonstrates control of molecule positioning with resolution limited only by the underlying patterned structure, does not require any alignment, is carried out entirely under biologically compatible conditions, and is scalable. PMID- 27559838 TI - On the tensile strength of insect swarms. AB - Collective animal groups are often described by the macroscopic patterns they form. Such global patterns, however, convey limited information about the nature of the aggregation as a whole. Here, we take a different approach, drawing on ideas from materials testing to probe the macroscopic mechanical properties of mating swarms of the non-biting midge Chironomus riparius. By manipulating ground based visual features that tend to position the swarms in space, we apply an effective tensile load to the swarms, and show that we can quasi-statically pull single swarms apart into multiple daughter swarms. Our results suggest that swarms surprisingly have macroscopic mechanical properties similar to solids, including a finite Young's modulus and yield strength, and that they do not flow like viscous fluids. PMID- 27559839 TI - Dosage Adjustment of Dabigatran Etexilate Based on Creatinine Clearance in Patients With Cardioembolic Stroke or Atrial Fibrillation. AB - BACKGROUND: A recommendation for dosage adjustment of dabigatran etexilate, a prodrug of dabigatran, seems to be desirable based on creatinine clearance to avoid bleeding and stroke. METHODS: Outpatients and inpatients having a history of cardioembolic stroke or atrial fibrillation were included. After taking dabigatran etexilate orally (75-150 mg twice daily) for at least 1 week, plasma trough concentration (Ctrough, ng/mL) of dabigatran and creatinine clearance (CLcr, mL/min) of patients according to Cockcroft and Gault equation were determined. RESULTS: Among the 38 patients studied, Ctrough of dabigatran and CLcr were scattered in a range from 31.4 to 329.5 ng/mL and 15.4-133.4 mL/min, respectively. Temporal CLtotal (Temp-CLtotal) of dabigatran, estimated by dividing the daily absorbed amount of dabigatran etexilate with Ctrough of dabigatran, was linearly correlated with CLcr of patients (P = 0.0018). Based on the findings, the daily dose of dabigatran etexilate that provides Ctrough of dabigatran at approximately 70 ng/mL was estimated. CONCLUSIONS: A linear relationship was found between Temp-CLtotal of dabigatran and CLcr of patients. Depending on CLxr of patients, we recommend 4 different dosages of dabigatran etexilate to obtain Ctrough of dabigatran at approximately 70 ng/mL. PMID- 27559840 TI - Efficiency and Safety of an Early Dose Adjustment of Ribavirin in Patients Infected With Hepatitis C Underexposed to the Drug and Treated With Peginterferon Ribavirin. AB - BACKGROUND: Ribavirin exposure after the first dose (D0AUC0-4h) >1755 mcg.h.L is predictive of sustained virological response (SVR) in patients with hepatitis C treated with peginterferon and ribavirin. The aim of this study was to test the benefit of ribavirin early dose adjustment based on this target in naive patients infected with genotype 1. METHODS: A multicenter randomized controlled trial with two parallel groups; fixed-dose (FD) group: standard of care in 2010-2011, ie, peginterferon-alpha2a 180 mcg.wk and weight-based ribavirin 1000-1200 mg/d during 48 weeks; adapted-dose (AD) group: increase of ribavirin dose if D0AUC0-4h <1755 mcg.h.L. RESULTS: A total of 221 patients were included, 110 in the AD group and 111 in the FD group with similar baseline characteristics. In the perprotocol analysis, SVR was higher in the AD group (55.1% versus 40.4%; P = 0.042), especially in patients with D0AUC0-4h <1755 mcg.h.L (54.3% versus 31.9%; P = 0.029). In the intention-to-treat analysis, the difference was not significant (50% versus 41%; P = 0.197). Ribavirin trough concentrations (C0s) at week 4 of treatment (intention-to-treat analysis) were higher in patients achieving SVR (2.06 versus 1.72 mg/L, P = 0.003). In the subgroup of patients with AUC0-4h <1755 mcg.h.L, 46% of patients with AD achieved a C0 >2.0 mg/L versus 22% of patients with FD (P = 0.013). Grade 1 anemia (but not other grades) was more frequent in the AD group (70% versus 48%, P = 0.001). The number of dose reductions or discontinuation of ribavirin was similar in both groups. CONCLUSIONS: Early ribavirin dose adjustment increases SVR in patients underexposed to ribavirin without increasing grade II-IV anemia. Such a strategy could be useful in patients with no access to new antiviral drugs. PMID- 27559841 TI - Effects of Miconazole Oral Gel on Blood Concentrations of Tacrolimus and Cyclosporine: A Retrospective Observational Study. AB - BACKGROUND: Although azole antifungal agents have been shown to affect the pharmacokinetics of calcineurin inhibitors such as tacrolimus (TAC) and cyclosporine (CyA) by inhibiting drug metabolism, there are few clinical reports on drug interactions between miconazole (MCZ) oral gel and calcineurin inhibitors. In this study, the effects of MCZ oral gel on the blood concentrations of TAC and CyA were investigated. METHODS: In this retrospective study, 18 patients concomitantly administered MCZ oral gel and TAC (9 for dermatomyositis, 3 for myasthenia gravis, 2 for systemic lupus erythematosus, 2 for rheumatoid arthritis, 1 for polymyositis, 1 for prevention of graft-versus host disease after bone marrow transplantation), and 15 patients concomitantly administered MCZ oral gel and CyA (11 for interstitial pneumonia, 2 for pemphigus, 1 for eosinophilic granulomatosis with polyangiitis, 1 for systemic lupus erythematosus) were evaluated. The dose-adjusted blood concentrations of TAC or CyA were compared before and after the initiation of MCZ oral gel. RESULTS: The trough blood concentration/dose (C/D) ratios of TAC and CyA increased significantly with the administration of MCZ oral gel. The median C/D ratios of TAC and CyA increased by 108% (range: -44% to 216%) and 44% (range: 34% to 195%), respectively. CONCLUSIONS: These results suggest that MCZ oral gel affects the pharmacokinetics of TAC and CyA. Detailed monitoring of the blood concentrations of these drugs, followed by dose adjustments, is needed for each patient because of the difficulties associated with accurately predicting the degree of the effects of MCZ oral gel. PMID- 27559842 TI - Twelve tips on setting up and running a peer-led medical education society. AB - Peer-led teaching is an established paradigm with benefits for student teachers, learners and the wider medical community. Students are increasingly taking ownership of such teaching, which has fuelled the creation of new peer-led medical education societies at universities around the UK. Students wishing to undertake such an endeavor must contend with concerns over the quality of peer led teaching, logistical challenges, lack of senior support and difficulties accessing relevant resources to design and appraise their initiatives. Peer-led medical education societies represent a relatively novel concept, and students may struggle to find practical information on how to approach these challenges. We propose that these obstacles can be overcome by thorough event planning, understanding the role and features of high quality peer-led education in supplementing medical school curricula, maintaining a strong working relationship with local medical faculty, and learning from the wider medical education community. PMID- 27559843 TI - National Laboratory Planning: Developing Sustainable Biocontainment Laboratories in Limited Resource Areas. AB - Strategic laboratory planning in limited resource areas is essential for addressing global health security issues. Establishing a national reference laboratory, especially one with BSL-3 or -4 biocontainment facilities, requires a heavy investment of resources, a multisectoral approach, and commitments from multiple stakeholders. We make the case for donor organizations and recipient partners to develop a comprehensive laboratory operations roadmap that addresses factors such as mission and roles, engaging national and political support, securing financial support, defining stakeholder involvement, fostering partnerships, and building trust. Successful development occurred with projects in African countries and in Azerbaijan, where strong leadership and a clear management framework have been key to success. A clearly identified and agreed management framework facilitate identifying the responsibility for developing laboratory capabilities and support services, including biosafety and biosecurity, quality assurance, equipment maintenance, supply chain establishment, staff certification and training, retention of human resources, and sustainable operating revenue. These capabilities and support services pose rate-limiting yet necessary challenges. Laboratory capabilities depend on mission and role, as determined by all stakeholders, and demonstrate the need for relevant metrics to monitor the success of the laboratory, including support for internal and external audits. Our analysis concludes that alternative frameworks for success exist for developing and implementing capabilities at regional and national levels in limited resource areas. Thus, achieving a balance for standardizing practices between local procedures and accepted international standards is a prerequisite for integrating new facilities into a country's existing public health infrastructure and into the overall international scientific community. PMID- 27559845 TI - A career in a Kingdom: Journeys in infection, Mass Gathering Medicine and public health diplomacy. PMID- 27559844 TI - RENEB accident simulation exercise. AB - PURPOSE: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event. MATERIALS AND METHODS: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants. The exercise was performed over 27 weeks and involved the network consisting of 28 institutes: 21 RENEB members, four candidates and three non-RENEB partners. RESULTS: The duration of a single exercise never exceeded 10 days, while the response from the assisting laboratories never came later than within half a day. During each week of the exercise, around 4500 samples were reported by all service laboratories (SL) to be examined and 54 scenarios were coherently estimated by all laboratories (the standard deviation from the mean of all SL answers for a given scenario category and a set of data was not larger than 3 patient codes). CONCLUSIONS: Each participant received training in both the role of a reference laboratory (activating the network) and of a service laboratory (responding to an activation request). The procedures in the case of radiological event were successfully established and tested. PMID- 27559846 TI - Depression Moderates the Relationship Between Pain and the Nonmedical Use of Opioid Medication Among Adult Outpatients. AB - BACKGROUND: The nonmedical use of prescription medication among US adults is a growing public health problem. Healthcare providers should proactively address this problem in outpatient encounters. OBJECTIVE: We sought to understand the interactive effects among prescription drugs, pain, and psychiatric symptoms among adult outpatients to build an empirical foundation for comprehensive screening. METHODS: We screened 625 adult neurosurgery and orthopedic patients at a suburban satellite clinic of an urban academic medical center. A convenience sample was screened for psychiatric and substance use disorder symptoms using the American Psychiatric Association's recommended screening protocol. We tested whether psychiatric symptoms moderated the relationship between pain level and nonmedical use of prescription medicine. RESULTS: Patients reported average levels of depression, anxiety, and pain symptoms, within 1 standard deviation of the screeners' normative data. However, patients reported highly elevated levels of nonmedical use of opioids and benzodiazapines compared with national data. Controlling for age, sex, and race, pain level predicted nonprescription use of opioid and benzodiazapine medications. Patients with high levels of depression and pain were more likely to engage in the unprescribed use of opioids. Likewise, patients with reduced levels of depression and pain were protected against the unprescribed use of opioids. CONCLUSIONS: These findings highlight the importance of examining unprescribed medication use even with patients at moderate levels of psychiatric symptoms and pain. PMID- 27559847 TI - Implementation of Motivational Interviewing in Substance Use Disorder Treatment: Research Network Participation and Organizational Compatibility. AB - INTRODUCTION: Despite considerable empirical evidence that psychosocial interventions improve addiction treatment outcomes across populations, implementation remains problematic. A small body of research points to the importance of research network participation as a facilitator of implementation; however, studies examined limited numbers of evidence-based practices. To address this gap, the present study examined factors impacting implementation of motivational interviewing (MI). METHODS: This study used data from a national sample of privately funded treatment programs (n = 345) and programs participating in the National Drug Abuse Treatment Clinical Trials Network (CTN) (n = 156). Data were collected via face-to-face interviews with program administrators and clinical directors (2007-2009). Analysis included bivariate t tests and chi-square tests to compare private and CTN programs, and multivariable logistic regression of MI implementation. FINDINGS: A majority (68.0%) of treatment programs reported use of MI. Treatment programs participating in the CTN (88.9%) were significantly more likely to report use of MI compared with non CTN programs (58.5%; P < 0.01). CTN programs (82.1%) also were more likely to use trainers from the Motivational Interviewing Network of Trainers as compared with private programs (56.1%; P < 0.05). Multivariable logistic regression models reveal that CTN-affiliated programs and programs with a psychiatrist on staff were more likely to use MI. Programs that used the Stages of Change Readiness and Treatment Eagerness Scale assessment tool were more likely to use MI, whereas programs placing greater emphasis on confrontational group therapy were less likely to use MI. DISCUSSION: Findings suggest the critical role of research network participation, access to psychiatrists, and organizational compatibility in adoption and sustained use of MI. PMID- 27559848 TI - Proximal disruption of base pairing of the second stem in the upper stem of pri miR156a caused ambient temperature-sensitive flowering in Arabidopsis. AB - MicroRNAs are generated from primary transcripts (pri-miRNAs) that form hairpin structures. Plant miRNAs play an important role in regulating flowering; however, little is known about the role of their structures in ambient temperature responsive flowering. We recently showed that disruption of base pairing in the second stem (S2) in the upper stem of pri-miR156a caused hypersensitive flowering in response to ambient temperature changes. To further substantiate our findings on the role of S2 of pri-miR156a, we analyzed the effects of serial disruption (from the proximal or distal sides) of base-pairing in S2 of pri-miR156a on temperature-dependent flowering. We found that flowering time was gradually delayed with increasing size of the proximal disruption of S2 at 16 degrees C. Particularly, disrupting base pairing of 5 nucleotides from the proximal side caused flowering to be hypersensitive to ambient temperature changes, which is similar to the phenotype of plants overexpressing pri-miR156a with a disruption of S2 (156-DBP-S2). However, disrupting base pairing from the distal side did not cause late flowering at 16 degrees C and thus did not cause temperature-sensitive flowering. These results supported our notion that the second stem (S2) in the upper stem of pri-miR156a plays a role in the regulation of ambient temperature responsive flowering. PMID- 27559849 TI - Metadata (ORCID) Correction: Effectiveness of Internet-Based Interventions for the Prevention of Mental Disorders: A Systematic Review and Meta-Analysis. AB - [This corrects the article DOI: 10.2196/mental.6061.]. PMID- 27559851 TI - Small Molecule Survivin Inhibitor YM155 Displays Potent Activity Against Human Osteosarcoma Cells. AB - Survivin is an important oncogenic protein expressed highly in osteosarcoma. Here, we have shown that small molecule inhibitor YM155 potently suppressed survivin expression, inhibited cell growth, and induced apoptosis in osteosarcoma cells. Furthermore, we also showed that knock down of survivin by small interfering RNA strongly inhibited cell viability in two osteosarcoma cell lines, suggesting that suppression of survivin essentially contributes to YM155-mediated anticancer activity in osteosarcoma cells. Collectively, our study suggests that YM155 holds promise for patients with osteosarcoma. PMID- 27559852 TI - Metabolic Health Status and the Obesity Paradox in Older Adults. AB - The explanation for reduced mortality among older persons with overweight or class I obesity compared to those of desirable weight remains unclear. Our objective was to investigate the joint effects of body mass index (BMI) and metabolic health status on all-cause mortality in a cohort of advanced age. Adults aged 74 +/- 4.7 (mean +/- SD) years at baseline (n = 4551) were categorized according to BMI (18.5-24.9, 25.0-29.9, 30.0-34.9, and >=35.0 kg/m(2)) and the presence or absence of a metabolically healthy phenotype (i.e., 0 or 1 risk factors based on a modified Adult Treatment Panel III). Metabolically unhealthy was >=2 risk factors. There were 2294 deaths over a mean 10.9 years of follow up. Relative to metabolically healthy desirable weight, metabolically healthy overweight or class I obesity was not associated with a greater mortality risk (HR 0.90; 95 CI% 0.73-1.13 and HR 0.58; 95 CI% 0.42-0.80, respectively) (P interaction <0.001). Results remained consistent in rigorous sensitivity analyses. The "obesity paradox" may be partially explained by the inclusion of metabolically healthy overweight and obese older persons, who do not have elevated mortality risk, in population studies of BMI and mortality. PMID- 27559850 TI - DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1. AB - Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, the development of resistance to cisplatin is a major obstacle in clinical therapy. The principal mechanism of cisplatin is the induction of DNA damage, thus the capability of DNA damage response (DDR) is a key factor that influences the cisplatin sensitivity of cancer cells. Recent advances have demonstrated that miRNAs (microRNAs) exerted critical roles in DNA damage response; nonetheless, the association between DNA damage responsive miRNAs and cisplatin resistance and its underlying molecular mechanism still require further investigation. The present study has attempted to identify differentially expressed miRNAs in cisplatin induced DNA damage response in lung cancer cells, and probe into the effects of the misexpressed miRNAs on cisplatin sensitivity. Deep sequencing showed that miR-33b-3p was dramatically down regulated in cisplatin-induced DNA damage response in A549 cells; and ectopic expression of miR-33b-3p endowed the lung cancer cells with enhanced survival and decreased gammaH2A.X expression level under cisplatin treatment. Consistently, silencing of miR-33b-3p in the cisplatin-resistant A549/DDP cells evidently sensitized the cells to cisplatin. Furthermore, we identified CDKN1A (p21) as a functional target of miR-33b-3p, a critical regulator of G1/S checkpoint, which potentially mediated the protection effects of miR-33b-3p against cisplatin. In aggregate, our results suggested that miR-33b-3p modulated the cisplatin sensitivity of cancer cells might probably through impairing the DNA damage response. And the knowledge of the drug resistance conferred by miR-33b-3p has great clinical implications for improving the efficacy of chemotherapies for treating lung cancers. PMID- 27559853 TI - Food Insecurity and Health Care Utilization Among Older Adults in the United States. AB - This study examined the relationships between food insecurity and utilization of four health services among older Americans: office visits, inpatient hospital nights, emergency department visits, and home health care. Nationally representative data from the 2011 and 2012 National Health Interview Survey were used (N = 13,589). Nearly 83.0% of the sample had two or more office visits, 17.0% reported at least one hospital night, 23.0% had at least one emergency room visit, and 8.1% used home health care during the past 12 months. Adjusting for confounders, food-insecure older adults had higher odds of using more office visits, inpatient hospital nights, and emergency department visits than food secure older adults, but similar odds of home health care utilization. The findings of this study suggest that programs and policies aimed at reducing food insecurity among older adults may have a potential to reduce utilization of health care services. PMID- 27559854 TI - Evaluation of Handgrip Strength and Nutritional Risk of Congregate Nutrition Program Participants in Florida. AB - The aim of this study was to determine if handgrip strength (HGS) is a predictor of nutritional risk in community-dwelling older adults. A cross-sectional study was carried out to determine the relationship between HGS and nutritional risk using SCREEN 1. The setting was Congregate Nutrition program meal sites (n = 10) in North Central Florida and included community-dwelling older adults participating in the Congregate Nutrition program. Older adults (n = 136; 77.1 +/ 8.9 y; 45 M, 91 F) participated in the study. Nutritional risk was identified in 68% of participants, with 10% exhibiting clinically relevant weakness (men, HGS < 26 kg; women, HGS < 16 kg), suggesting a vulnerable population. HGS was weakly associated with nutritional risk as assessed by SCREEN 1 (AUC = 0.59), but alternate cutpoints, 33 kg for men (mean of both hands) and 22 kg for women (highest of either hand), provided the best comparison to nutritional risk. In community-dwelling older adults, HGS was weakly associated with nutritional risk assessed using traditional screening. However, as existing research supports the inclusion of HGS in malnutrition screening in acute care, further research into the usefulness of HGS and possibly other measures of functional status in nutrition risk screening of community-dwelling older adults may be warranted. PMID- 27559855 TI - Effect of Ginger Supplementation on Proinflammatory Cytokines in Older Patients with Osteoarthritis: Outcomes of a Randomized Controlled Clinical Trial. AB - There is limited evidence that ginger powder consumption can relieve pain and inflammation due to specific anti-inflammatory phytochemical constitutents. This study investigates the effect of ginger supplementation on proinflammatory factors in participants (n = 120) of a randomized double-blind placebo-controlled 3-month clinical trial investigating knee osteoarthritis. Patients were randomly assigned to one of two groups: the ginger group (GG) or the placebo group (PG). Administered daily for 3 months, participants in the GG intervention received capsules containing 500 mg of ginger powder, while PG participants received capsules filled with 500 mg starch. Serum samples collected at baseline and 3 months were analyzed for serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). At baseline, proinflammatory cytokine concentrations did not differ by group. However, at 3 months, both cytokines decreased in the GG relative to the PG. The results of this study indicate that ginger supplementation may have a promising benefits for knee osteoarthritis and may, therefore, may warrant further study. PMID- 27559857 TI - Randomized controlled trial of the Resilience and Coping Intervention (RCI) with undergraduate university students. AB - OBJECTIVE: The purpose of this pilot study was to evaluate the Resilience and Coping Intervention (RCI) with college students. PARTICIPANTS: College students (aged 18-23) from a large Midwest US university who volunteered for a randomized controlled trial during the 2015 spring semester. METHODS: College students were randomly assigned to an intervention (n = 64) or a control (n = 65) group. Intervention participants received three 45-minute RCI sessions over subsequent weeks. All participants completed pre- and post-intervention assessments at the beginning of Week 1 and end of Week 3. Student resilience, coping, hope, stress, depression, and anxiety were assessed. RESULTS: RCI participants reported significantly more hope and less stress and depression from Week 1 to Week 3 compared with control participants. Results for resilience also approached statistical significance. Effect sizes were small to moderate. CONCLUSIONS: This study found preliminary evidence that RCI is an effective resilience intervention for use with college students. PMID- 27559858 TI - The Relationship Between Skinfold Thickness and Leptin, Ghrelin, Adiponectin, and Resistin Levels in Infants of Diabetic Mothers. AB - This study aimed to investigate the relationship between skinfold thickness and serum leptin, ghrelin, adiponectin, and resistin levels in infants of diabetic mothers. Biochemical parameters were also similar for the two groups (infants of diabetic mothers and controls) (p > 0.05). We confirmed that there was a negative correlation between birth weight and serum ghrelin level (p < 0.05) in the two groups. When it was evaluated for control newborns, a positive correlation between abdominal circumference and serum resistin level was found in the controls (p < 0.05). Our results indicate that gestational diabetes by appropriate diet or insulin treatment may be effective in the protection of fetuses of diabetic mothers from the negative effects of gestational diabetes. Ghrelin alone was negatively correlated with birth weight. This negative correlation could be potentially advantageous to infants, because a reduction in appetite might prevent excessive food intake and postnatal weight gain. PMID- 27559856 TI - ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2. AB - Autophagy critically contributes to metabolic reprogramming and chromosomal stability. It has been reported that monoallelic loss of the essential autophagy gene BECN1 (encoding BECN1/Beclin 1) promotes cancer development and progression. However, the mechanism by which BECN1 is inactivated in malignancy remains largely elusive. We have previously reported a tumor suppressor role of ABHD5 (abhydrolase domain containing 5), a co-activator of PNPLA2 (patatin like phospholipase domain containing 2) in colorectal carcinoma (CRC). Here we report a noncanonical role of ABHD5 in regulating autophagy and CRC tumorigenesis. ABHD5 directly competes with CASP3 for binding to the cleavage sites of BECN1, and consequently prevents BECN1 from being cleaved by CASP3. ABHD5 deficiency provides CASP3 an advantage to cleave and inactivate BECN1, thus impairing BECN1 induced autophagic flux and augmenting genomic instability, which subsequently promotes tumorigenesis. Notably, clinical data also confirm that ABHD5 proficiency is significantly correlated with the expression levels of BECN1, LC3 II and CASP3 in human CRC tissues. Our findings suggest that ABHD5 possesses a PNPLA2-independent function in regulating autophagy and tumorigenesis, further establishing the tumor suppressor role of ABHD5, and offering an opportunity to develop new approaches aimed at preventing CRC carcinogenesis. PMID- 27559917 TI - Identifying motivators and barriers to older community-dwelling people participating in resistance training: A cross-sectional study. AB - Participation rates of older people in resistance training (RT) are low despite increasing research showing many health benefits. To increase the number of older people participating in RT it is important to know what would motivate people to become involved, what motivates those who participate to continue, and the factors preventing many older people from commencing participation. To investigate these issues, a questionnaire was mailed to three groups of older people: (1) those receiving home care services, (2) members of a peak non government seniors' organisation and (3) those participating in a specific gym based RT programme. In total, 1327 questionnaires were returned (response rate = 42.5%). To feel good physically and mentally were the main reasons motivating participation among all three groups, and falls prevention was identified as an important motivator for the home care respondents. Pain, injury and illness were the main barriers to participating, or continuing to participate. However, medical advice was a factor influencing participation commencement. The results suggest organisations providing RT programmes for older people should tailor the promotion and delivery of programmes to address key motivators and barriers specific to each group to increase the proportion of older people initiating and continuing to engage in RT. PMID- 27559918 TI - The Load Model: an alternative to QALY. AB - BACKGROUND: QALYs are widely used in health economic evaluation, but remain controversial, largely because they do not reflect how many people behave in practice. This paper presents a new conceptual model (Load Model) and illustrates it in comparison with the QALY model. METHODS: Load is the average annual weight attributed to morbidity and mortality over a defined period, using weightings based on preference judgements. Morbidity Load is attributed to states of illness, according to their perceived severity. When people are in full health, Load is zero (no morbidity). Death is treated as an event with negative consequences, incurred in the year following death. Deaths may be weighted equally, with a fixed negative weight such as -100, or differ according to the context of death. After death, Load is zero. In a worked example, we use the standard gamble method to obtain a weighting for an illness state, for both Load and QALY models. A judge is indifferent between certainty of 1.5 years' illness followed by death, or a 50/50 chance of 1.5 years' full health or 1-year illness, each followed by death. The weightings calculated are applied to a hypothetical life, 72 years in full health followed by 3 years with illness then death, using both models. Three other hypothetical outcomes are also compared. RESULTS: For an example life, the relative size of the morbidity component compared with the mortality component is much higher in the Load model than in the QALY model. When comparing alternative outcomes, there are also substantial differences between the two models. CONCLUSIONS: In the Load model the weight of morbidity, relative to mortality, is very different from that in the QALY model. Given the role of the QALYs in economic evaluation, the implications of an alternative, which generates very different results, warrant further exploration. PMID- 27559919 TI - Modeling the Future. PMID- 27559920 TI - Principles of Systems Biology, No. 8. AB - Advances in biological engineering headline this month's Cell Systems call (Cell Systems 1, 307), alongside intriguing applications of modeling from the Elf, Goentoro, and Wolf groups. Check out our recent blogpost: http://crosstalk.cell.com/blog/a-call-for-papers-on-biological-engineering-and synthetic-biology. PMID- 27559921 TI - Cellular Advantages to Signaling in a Digital World. AB - A newly revealed cellular strategy for modularizing function inspires engineers. PMID- 27559922 TI - Sensing the Right Time to Be Productive. AB - Engineered E. coli can be made to autonomously switch from growth to production by a modular two-gate system that reduces the burden of biosynthesis. PMID- 27559923 TI - SYGNALing a Red Light for Glioblastoma. AB - A new multiomic network inference pipeline, SYGNAL, integrates patient data with mechanistically accurate transcriptional regulatory networks to predict drug combinations with synergistic anti-proliferative effects on glioblastoma multiforme. PMID- 27559924 TI - A Two-Layer Gene Circuit for Decoupling Cell Growth from Metabolite Production. AB - We present a synthetic gene circuit for decoupling cell growth from metabolite production through autonomous regulation of enzymatic pathways by integrated modules that sense nutrient and substrate. The two-layer circuit allows Escherichia coli to selectively utilize target substrates in a mixed pool; channel metabolic resources to growth by delaying enzymatic conversion until nutrient depletion; and activate, terminate, and re-activate conversion upon substrate availability. We developed two versions of controller, both of which have glucose nutrient sensors but differ in their substrate-sensing modules. One controller is specific for hydroxycinnamic acid and the other for oleic acid. Our hydroxycinnamic acid controller lowered metabolic stress 2-fold and increased the growth rate 2-fold and productivity 5-fold, whereas our oleic acid controller lowered metabolic stress 2-fold and increased the growth rate 1.3-fold and productivity 2.4-fold. These results demonstrate the potential for engineering strategies that decouple growth and production to make bio-based production more economical and sustainable. PMID- 27559925 TI - Pentaleno[1,2-a:4,5']diacenaphthylenes: Uniquely Stabilized Pentalene Derivatives. AB - We demonstrate the preparation of diacenaphthopentalene derivatives via a palladium-catalyzed dimerization of 1-iodo-2-arylethynyl-acenaphthylenes. The resulting 7,14-diarylpentaleno[1,2-a:4,5a']diacenaphthylenes, which contain four linearly fused five-membered rings, are benchtop stable and behave as hole transporting or ambipolar semiconductors in organic field effect transistors. The X-ray crystal structure shows the important role of the fused naphthalene unit that enforces a formal pentalene subunit at the central five-membered rings and [5]-radialene-like structures at the proximal five-membered rings. Nucleus independent chemical shift (NICS) calculations show the internal pentalene rings are intermediate in antiaromaticity character between known pentalene and dibenzopentalenes derivatives. The diacenaphthopentalene derivatives give high optical gap materials owing to a forbidden HOMO to LUMO transition, yet have narrow electrochemical gaps and are reduced at small negative potentials giving LUMO energy levels of -3.57 to -3.74 eV. PMID- 27559926 TI - Superabsorbent 3D Scaffold Based on Electrospun Nanofibers for Cartilage Tissue Engineering. AB - Electrospun nanofibers have been used for various biomedical applications. However, electrospinning commonly produces two-dimensional (2D) membranes, which limits the application of nanofibers for the 3D tissue engineering scaffold. In the present study, a porous 3D scaffold (3DS-1) based on electrospun gelatin/PLA nanofibers has been prepared for cartilage tissue regeneration. To further improve the repairing effect of cartilage, a modified scaffold (3DS-2) cross linked with hyaluronic acid (HA) was also successfully fabricated. The nanofibrous structure, water absorption, and compressive mechanical properties of 3D scaffold were studied. Chondrocytes were cultured on 3D scaffold, and their viability and morphology were examined. 3D scaffolds were also subjected to an in vivo cartilage regeneration study on rabbits using an articular cartilage injury model. The results indicated that 3DS-1 and 3DS-2 exhibited superabsorbent property and excellent cytocompatibility. Both these scaffolds present elastic property in the wet state. An in vivo study showed that 3DS-2 could enhance the repair of cartilage. The present 3D nanofibrous scaffold (3DS-2) would be promising for cartilage tissue engineering application. PMID- 27559927 TI - Shelterin Telomere Protection Protein 1 Reduction Causes Telomere Attrition and Cellular Senescence via Sirtuin 1 Deacetylase in Chronic Obstructive Pulmonary Disease. AB - Lung cellular senescence and inflammatory response are the key events in the pathogenesis of chronic obstructive pulmonary disease (COPD) when cigarette smoke (CS) is the main etiological factor. Telomere dysfunction is induced by either critical shortening or disruption of the shelterin complex, leading to cellular senescence. However, it remains unknown whether disruption of the shelterin complex is responsible for CS-induced lung cellular senescence. Here we show that telomere protection protein 1 (TPP1) levels are reduced on telomeres in lungs from mice with emphysema, as well as in lungs from smokers and from patients with COPD. This is associated with persistent telomeric DNA damage, leading to cellular senescence. CS disrupts the interaction of TPP1 with the Sirtuin 1 (Sirt1) complex, leading to increased TPP1 acetylation and degradation. Lung fibroblasts deficient in Sirt1 or treated with a selective Sirt1 inhibitor exhibit increased cellular senescence and decreased TPP1 levels, whereas Sirt1 overexpression and pharmacological activation protect against CS-induced TPP1 reduction and telomeric DNA damage. Our findings support an essential role of TPP1 in protecting CS-induced telomeric DNA damage and cellular senescence, and therefore provide a rationale for a potential therapy for COPD, on the basis of the shelterin complex, in attenuating cellular senescence. PMID- 27559928 TI - Cortisol response to family interaction as a predictor for adjustment. AB - Emerging adult (EA) cortisol response during family interaction predicts change in EA anxious behavior during the transition to college (Johnson & Gans, in press). In the present study, we take an initial step toward integrating family systems research and physiology by including assessment of EA salivary cortisol collected during a triadic (mother-father-EA offspring) family interaction task. Emerging adults (N = 101) between the ages of 17 and 19 were assessed at 3 time points across their first college year: the summer before college, Fall and Spring semesters. Two parents accompanied the emerging adult child to the summer assessment; all family members provided 4 saliva samples each at 20-min intervals. Later assessments of emerging adults included measures of internalizing behaviors. EA's cortisol secretion patterns during family interaction predict observed and self-reported family relatedness, as well as patterns of internalizing behavior during the college transition. Observed family functioning appeared to moderate the relationship between EA cortisol response during family interaction and anxious behavior when adapting to college. Different patterns of results emerged, however, for EA men and women. The approach taken by this study provides a first step toward understanding how interrelationships among elements of physiology and family functioning contribute to later adjustment. (PsycINFO Database Record PMID- 27559929 TI - Parental insightfulness is associated with cooperative interactions in families with toddlers. AB - A growing body of research has highlighted the importance of mother-father-child interactions in families with toddlers, but little is known about the internal processes underlying parenting in such interactions. Dyadic studies of parent child relationships have focused on parental insightfulness as promoting sensitive parent-child interactions, and the goal of the present study was to examine whether insightfulness would similarly be associated with cooperative triadic interactions. To address this question, we observed 77 mother-father toddler triads in the Lausanne Trilogue Play (LTP) procedure to assess family cooperation, and the insightfulness of each parent was assessed using the Insightfulness Assessment, a video replay procedure in which parents are interviewed regarding their children's thoughts and feelings after watching short video clips of the children. The results showed that families in which both parents were insightful had higher Family Cooperation and Coparenting scores compared to families in which only 1 parent was insightful and families in which neither parent was insightful. The implications of these findings for research on the internal processes underlying parenting in a triadic context are discussed. (PsycINFO Database Record PMID- 27559930 TI - Activation of the Class Ib Ribonucleotide Reductase by a Flavodoxin Reductase in Bacillus cereus. AB - To reduce ribonucleotides to deoxyribonucleotides, the manganese-bound form of class Ib ribonucleotide reductase (RNR) must be activated via a pathway that involves redox protein(s). The reduced flavoprotein NrdI is an important protein in this pathway, as it reduces dioxygen to superoxide. Superoxide then reacts with the RNR Mn(II)2 site to generate a tyrosyl radical that is required for catalysis. A native NrdI reductase has not yet been identified. We herein demonstrate through kinetic and spectroscopic studies that an endogenous flavodoxin reductase can function as the NrdI reductase in Bacillus cereus. When the flavodoxin reductase reduces NrdI, tyrosyl radical formation in RNR is promoted under aerobic conditions, significantly increasing the radical yield. Thus, a missing piece of the class Ib RNR NrdI redox pathway has finally been identified. PMID- 27559931 TI - Low-Power Miniaturized Helium Dielectric Barrier Discharge Photoionization Detectors for Highly Sensitive Vapor Detection. AB - This paper presents the design, fabrication, and characterization of a microhelium dielectric barrier discharge photoionization detector (MUHDBD-PID) on chip with dimensions of only ~15 mm * ~10 mm * ~0.7 mm and weight of only ~0.25 g. It offers low power consumption (<400 mW), low helium consumption (5.8 mL/min), rapid response (up to ~60 ms at a flow rate of 1.5 mL/min), quick warm up time (~5 min), an excellent detection limit (a few picograms), a large linear dynamic range (>4 orders of magnitude), and maintenance-free operation. Furthermore, the MUHDBD-PID can be driven with a miniaturized (~5 cm * ~2.5 cm * ~2.5 cm), light (22 g), and low cost (~$2) power supply with only 1.5 VDC input. The dependence of the MUHDBD-PID performance on bias voltage, auxiliary helium flow rate, carrier gas flow rate, and temperature was also systematically investigated. Finally, the MUHDBD-PID was employed to detect permanent gases and a sublist of the EPA 8260 standard reagents that include 51 analytes. The MUHDBD PID developed here can have a broad range of applications in portable and microgas chromatography systems for in situ, real-time, and sensitive gas analysis. PMID- 27559933 TI - Resource-Efficient High-Yield Ionothermal Synthesis of Microcrystalline Cu3-xP. AB - Polycrystalline Cu3-xP was successfully synthesized in different ionic liquids comprising imidazolium and phosphonium cations. The reaction of elemental copper and red phosphorus in trihexyltetradecylphosphonium chloride at 200 degrees C led to single-phase Cu3-xP (x = 0.05) within 24 h with a quantitative yield (99%). Liquid-state nuclear magnetic resonance spectroscopy of the ionic liquids revealed degeneration of the imidazolium cations under the synthesis conditions, while phosphonium cations remain stable. The solid products were characterized with X-ray powder diffraction, scanning electron microscopy, energy-dispersive X ray spectroscopy, solid-state nuclear magnetic resonance spectroscopy, and elemental analysis. A reinvestigation of the electronic transport properties of Cu2.95(4)P showed metallic behavior for the bulk material. The formation of CuP2 during the synthesis of phosphorus-rich Cu3-xP (x >= 0.1) was observed. PMID- 27559932 TI - Does Nature Know Best? Pericyclic Reactions in the Daphniphyllum Alkaloid-Forming Cation Cascade. AB - Heathcock's classic cyclization/rearrangement cascade for formation of Daphniphyllum alkaloids is subjected to analysis using density functional theory calculations. The results of these calculations are consistent with a two-step pathway involving two pericyclic reactions, a Diels-Alder cycloaddition and an ene reaction. PMID- 27559934 TI - Hybrid materials based on ruthenium and fullerene assemblies. AB - This review provides a detailed overview about the synthesis, properties and applications of all ruthenium-fullerene compounds reported within the last 25 years. The incorporation of ruthenium centers into fullerene compounds by organometallic, covalent or non-covalent bonds has led to a broad range of useful hybrid materials. By this approach novel compounds could be generated that feature the electron-donating and electron-accepting character of ruthenium complexes and fullerenes, respectively. Intramolecular interactions between both units could result in new, combined properties that were studied in the spotlight of emerging applications, such as photovoltaics or catalysis. PMID- 27559935 TI - Notes from the Field: Outbreak of Listeriosis Associated with Consumption of Packaged Salad - United States and Canada, 2015-2016. AB - In September 2015, PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified a cluster of Listeria monocytogenes (Listeria) clinical isolates indistinguishable by two-enzyme pulsed-field gel electrophoresis (PFGE) pattern combination and highly related by whole-genome multilocus sequence typing (wgMLST). A case was defined as isolation of Listeria with the outbreak PFGE pattern and highly related by wgMLST with an isolation date on or after July 5, 2015, the isolate date of the earliest case in this cluster. PMID- 27559937 TI - Reaching the south: metal-catalyzed transformation of the aromatic para-position. AB - Regioselective functionalization of aromatic arenes has created a rapid insurgence in the modern era of organic chemistry. While the last few years have witnessed significant developments on site-selective ortho- and meta-C-H transformations, there existed very few reports on para-C-H functionalization. Recent advancements on template assisted protocols in para-C-H activation has emerged as a popular and convenient feat in this area. This review highlights the various protocols developed over the years for selective installation of suitable functional groups at the para-position of arenes thereby transforming them into value-added organic cores. PMID- 27559936 TI - Discovery of S3-Truncated, C-6 Heteroaryl Substituted Aminothiazine beta-Site APP Cleaving Enzyme-1 (BACE1) Inhibitors. AB - Truncation of the S3 substituent of the biaryl aminothiazine 2, a potent BACE1 inhibitor, led to a low molecular weight aminothiazine 5 with moderate activity. Despite its moderate activity, compound 5 demonstrated significant brain Abeta reduction in rodents. The metabolic instability of 5 was overcome by the replacement of the 6-dimethylisoxazole, a metabolic soft spot, with a pyrimidine ring. Thus, truncation of the S3 substituent represents a viable approach to the discovery of orally bioavailable, brain-penetrant BACE1 inhibitors. PMID- 27559938 TI - A cohort study of tibialis anterior tendon shortening in combination with calf muscle lengthening in spastic equinus in cerebral palsy. AB - The aim of this study was to evaluate the outcome of combined tibialis anterior tendon shortening (TATS) and calf muscle-tendon lengthening (CMTL) in spastic equinus. Prospectively collected data was analysed in 26 patients with hemiplegic (n=13) and diplegic (n=13) cerebral palsy (CP) (GMFCS level I or II, 14 males, 12 females, age range 10-35 years; mean 16.8 years). All patients had pre-operative 3D gait analysis and a further analysis at a mean of 17.1 months (+/-5.6months) after surgery. None was lost to follow-up. Twenty-eight combined TATS and CMTL were undertaken and 19 patients had additional synchronous multilevel surgery. At follow-up 79% of patients had improved foot positioning at initial contact, whilst 68% reported improved fitting or reduced requirement of orthotic support. Statistically significant improvements were seen in the Movement Analysis Profile for ankle dorsi-/plantarflexion (4.15 degrees , p=0.032), maximum ankle dorsiflexion during swing phase (11.68 degrees , p<0.001), and Edinburgh Visual Gait Score (EVGS) (4.85, p=0.014). Diplegic patients had a greater improvement in the EVGS than hemiplegics (6.27 -vs- 2.21, p=0.024). The originators of combined TATS and CMTL showed that it improved foot positioning during gait. The present study has independently confirmed favourable outcomes in a similar patient population and added additional outcome measures, the EVGS, foot positioning at initial contact, and maximum ankle dorsiflexion during swing phase. Study limitations include short term follow-up in a heterogeneous population and that 19 patients had additional surgery. TATS combined with CMTL is a recommended option for spastic equinus in ambulatory patients with CP. PMID- 27559939 TI - Ten weeks of physical-cognitive-mindfulness training reduces fear-avoidance beliefs about work-related activity: Randomized controlled trial. AB - People with chronic musculoskeletal pain often experience pain-related fear of movement and avoidance behavior. The Fear-Avoidance model proposes a possible mechanism at least partly explaining the development and maintenance of chronic pain. People who interpret pain during movement as being potentially harmful to the organism may initiate a vicious behavioral cycle by generating pain-related fear of movement accompanied by avoidance behavior and hyper-vigilance.This study investigates whether an individually adapted multifactorial approach comprised of biopsychosocial elements, with a focus on physical exercise, mindfulness, and education on pain and behavior, can decrease work-related fear-avoidance beliefs.As part of a large scale 10-week worksite randomized controlled intervention trial focusing on company initiatives to combat work-related musculoskeletal pain and stress, we evaluated fear-avoidance behavior in 112 female laboratory technicians with chronic neck, shoulder, upper back, lower back, elbow, and hand/wrist pain using the Fear-Avoidance Beliefs Questionnaire at baseline, before group allocation, and again at the post intervention follow up 10 weeks later.A significant group by time interaction was observed (P < 0.05) for work-related fear-avoidance beliefs. The between-group difference at follow up was -2.2 (-4.0 to -0.5), corresponding to a small to medium effect size (Cohen's d = 0.30).Our study shows that work-related, but not leisure time activity-related, fear-avoidance beliefs, as assessed by the Fear-avoidance Beliefs Questionnaire, can be significantly reduced by 10 weeks of physical cognitive-mindfulness training in female laboratory technicians with chronic pain. PMID- 27559940 TI - Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan. AB - Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment. PMID- 27559941 TI - Development-associated immunophenotypes reveal the heterogeneous and individualized early responses of adult B-acute lymphoblastic leukemia. AB - B cell acute lymphoblastic leukemia (B-ALL) exhibits phenotypes reminiscent of normal stages of B-cell development. As demonstrated by flow cytometry, the immunophenotypes are able to determine the stages of B cell development. Multicolor flow cytometry (MFC) is more accurate at identifying cell populations. In this study, 9-color panels, including CD10, CD19, CD20, CD22, CD34, CD79a, CD179a, and IgM, which are sequentially expressed during B cell development, were designed to detect the leukemia cell subpopulations in adult B-ALL patients. In 23 patients at diagnosis, 192 heterogeneous subpopulations of leukemia cells were detected. Compared with their counterparts at diagnosis and after the 1st course of induction therapy, the responses of the subpopulations were also heterogeneous. In the CD10 population, the residual B cell subpopulations in the BCR/ABL patients were obviously reduced compared to those in the BCR/ABL patients. New subpopulations were detected in 22 of 23 patients and were primarily located in the CD34CD10 populations. Subpopulations of clonal evolution were heterogeneous after induction therapy. Our results suggest that the subpopulations in B-ALL patients should be dynamically monitored by development associated immunophenotyping before, during, and after induction therapy and to predict the prognosis of the disease. PMID- 27559942 TI - Mixed serous neuroendocrine neoplasm of the pancreas: Case report and literature review. AB - INTRODUCTION: The aim of this study was to report a new case of mixed serous neuroendocrine neoplasm (MSNN) and review the literature concerning this type of lesion, which was added to the World Health Organization classification of pancreatic tumors in 2010. RESULTS: A 73-year-old woman presented with a pancreatic mass. The lesion was an intriguing combination of serous cystic neoplasm (SCN) and pancreatic neuroendocrine tumor (PanNET), in which the PanNET component grew into the wall of the serous oligocystic adenoma. We searched different databases for studies that had investigated MSNN. A total of 15 patients (age, 28-78), including the patient in the present study, were evaluated. We discuss these cases in detail especially regarding morphology and pathology; our case was the only one involving a collision type combination. CONCLUSION: Although MSNN is recognized as a variant of SCN, it is quite different from SCN or PanNET. A new morphological analysis of MSNN may help in elucidating its histogenesis and prognosis. PMID- 27559943 TI - Increased risk of hemorrhage in metastatic colorectal cancer patients treated with bevacizumab: An updated meta-analysis of 12 randomized controlled trials. AB - BACKGROUND: As an important antivascular endothelial growth factor monoclonal antibody, bevacizumab has been administrated for the treatment of cancer patients. Hemorrhage, one of the common adverse events of angiogenesis inhibitors, sometimes is also fatal and life-threatening. We aimed at determining the incidence and risk of hemorrhage associated with bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: We searched PubMed, EMBASE, and the Web of Science databases for relevant randomized controlled trials (RCTs). The overall incidence, overall relative risk (RR), and 95% confidence interval (CI) were calculated by using a random-effects or fixed-effects model based on the heterogeneity of selected trials. RESULTS: A total of 10,555 mCRC patients from 12 RCTs were included in our study. The overall incidence of hemorrhage was 5.8% (95% CI 3.9%-7.8%). Bevacizumab significantly increased the overall risk of hemorrhage with an RR of 1.96 (95% CI 1.27-3.02). The RR of all-grade hemorrhage was 2.39 (95% CI 1.09-5.24) and 1.41 (95% CI 1.01-1.97) for high-grade hemorrhage. The risk of hemorrhage associated with bevacizumab was dose-dependent with an RR of 1.73 (95% CI 1.15-2.61) for 2.5 mg/kg/wk and 4.67 (95% CI 2.36 9.23) for 5 mg/kg/wk. More importantly, the RR of hemorrhage for treatment duration (<= 6 months and > 6 months) based on subgroup analysis was 4.13 (95% CI 2.58-6.61) and 1.43 (95% CI 0.96-2.14), respectively. CONCLUSION: The addition of bevacizumab to concurrent antineoplastic in patients with mCRC significantly increased the risk of hemorrhage. The dose of bevacizumab may contribute to the risk of hemorrhage. And the 1st 6 months of treatment may be a crucial period when hemorrhagic events occur. PMID- 27559944 TI - 18F-FDG PET/CT as a central tool in the shift from chronic Q fever to Coxiella burnetii persistent focalized infection: A consecutive case series. AB - Because Q fever is mostly diagnosed serologically, localizing a persistent focus of Coxiella burnetii infection can be challenging. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) could be an interesting tool in this context.We performed a retrospective study on patients diagnosed with C burnetii infection, who had undergone F-FDG PET/CT between 2009 and 2015. When positive F-FDG PET/CT results were obtained, we tried to determine if it changed the previous diagnosis by discovering or confirming a suspected focus of C burnetii infection.One hundred sixty-seven patients benefited from F-FDG PET/CT. The most frequent clinical subgroup before F-FDG PET/CT was patients with no identified focus of infection, despite high IgG1 serological titers (34%). For 59% (n = 99) of patients, a hypermetabolic focus was identified. For 62 patients (62.6%), the positive F-FDG PET/CT allowed the diagnosis to be changed. For 24 of them, (38.7%), a previously unsuspected focus of infection was discovered. Forty two (42%) positive patients had more than 1 hypermetabolic focus. We observed 21 valvular foci, 34 vascular foci, and a high proportion of osteoarticular localizations (n = 21). We also observed lymphadenitis (n = 27), bone marrow hypermetabolism (n = 11), and 9 pulmonary localizations.We confirmed thatF-FDG PET/CT is a central tool in the diagnosis of C burnetii focalized persistent infection. We proposed new diagnostic scores for 2 main clinical entities identified using F-FDG PET/CT: osteoarticular persistent infections and lymphadenitis. PMID- 27559945 TI - Comparisons of clinical outcomes in patients with and without a preoperative tissue diagnosis in the persistent malignant-looking, ground-glass-opacity nodules. AB - To evaluate the clinical usefulness of surgical resection of persistent malignant looking ground-glass-opacity nodules (GGN) without a preoperative tissue diagnosis.From September 1998 to November 2011, we retrospectively enrolled 288 patients (126 men, 162 women; mean age, 59.3 years) with lung adenocarcinoma proven by surgery and which appeared as GGN on chest computed tomography (CT, ground-glass-opacity [GGO] proportion >20%). We divided the study subjects into 2 groups: patients with a preoperative tissue diagnosis (PTD group, n = 207) and patients without a preoperative tissue diagnosis (No-PTD group, n = 81). In patients with GGN having GGO >= 90% (n = 140), we divided them into 2 groups: PTD group (n = 83) and No-PTD group (n = 57). The clinical and surgical outcomes were compared between the 2 groups.In 204 patients who underwent lobectomy for stage Ia lung cancer, there was no significantly different recurrence-free survival between the 2 groups (P = 0.721). A significantly lower percentage of No-PTD group waited >14 days for surgery (77.8% vs 87.9%, P = 0.030) and were hospitalized for >7 days (56.8% vs 89.9%, P < 0.001). They showed a shorter mean surgery time (136.9 vs 155.0 minutes, P = 0.019). In patients with GGN having GGO >= 90%, the results were the same as those of all of the study subjects.No-PTD group can gain benefits perioperatively, showing no different recurrence-free survival with PTD group in stage Ia lung cancer. PMID- 27559946 TI - Five-year follow-up of pulmonary embolism under anticoaugulation: The PISA-PEET (Pulmonary Embolism Extension Therapy) study. AB - Benefits and harms of long-term anticoagulant therapy (AT) after acute pulmonary embolism (PE) are poorly known. The aim of this study was to investigate the outcome of patients with PE treated with AT for 5 years according to American College of Chest Physicians (ACCP) guidelines.Patients with both unprovoked and secondary PE were consecutively enrolled in a "real life" study. After a 12-month AT, they continued or stopped the treatment according to ACCP guidelines, and were followed-up for 5 years. Outcomes were all-cause mortality, recurrence, and fatal recurrence under AT.Of the original consecutive 585 patients, 471 were included (83 dead, 31 lost during the 1st year). Of these, 361 (76.6%) continued AT. During 5 years, death occurred in 109 (30.2%) patients, with a mortality rate of 8.00 events/100 person-years of follow-up; recurrence in 34 (9.4%), with an incidence rate of 2.58 events/person-years; fatal recurrence in 13 (3.6%), with an incidence rate of 0.95 events/person-years. The case fatality rate for recurrence was 38.2%. In the subgroup of patients with unprovoked PE, the chance of dying was significantly lower (RR 0.35; 95% confidence interval 0.24-0.53) and the tendency to fatal recurrence (not significantly) greater (0.11 events/100 person-years vs 0.07 events/100 person-years) than in the remaining patients. Major bleeding occurred in 5 (1.3%) patients. The case fatality rate for bleeding was 14.3%.During 5-year AT, 30% of patients dies, 10% experiences recurrences, and 5% has fatal recurrences. According to guidelines, most patients need to continue AT; the case fatality rate for bleeding is lower than that for recurrence. PMID- 27559947 TI - Protective effect of an improved immunization practice of mother-to-infant transmission of hepatitis B virus and risk factors associated with immunoprophylaxis failure. AB - Although routine immunoprophylaxis has been known to reduce hepatitis B virus (HBV) transmission, immunoprophylaxis failure still occurs. The study aimed to investigate the protective efficacy of an improved immunoprophylaxis protocol to prevent mother-to-infant transmission of HBV and to explore the potential risk factors associated with immunoprophylaxis failure and low antibody response.A prospective observational cohort study was conducted from July 2012 to April 2015. A total of 863 HBsAg-positive mothers and their 871 infants (8 pairs of twins) were included in the study. Two different hepatitis B vaccine doses (20 or 10 MUg) were administered to the infants based on the hepatitis B e-antigen (HBeAg) status of their mothers. Simultaneously, hepatitis B immunoglobulin (HBIG) was administered to the infants. Initial injections of HBIG and the hepatitis vaccine were given within 2 hours after birth. Rates of HBV infections among the infants were evaluated at 7 months of age. Factors associated with immunoprophylaxis failure and low responses to vaccination were analyzed by unconditional logistic regression..At 7 months of age, no immunoprophylaxis failure was observed in the 565 infants born to HBeAg-negative mothers. Among the 306 infants born to HBeAg-positive mothers, immunoprophylaxis failed in 16 infants (5.2%) of the infants and they were found to be HBsAg-positive. Further analysis showed that HBV DNA levels >=10 IU/mL [odds ratio (OR) = 4.53, 95% confidence interval (95% CI): 1.19-17.34], delayed vaccination (OR = 4.14, 95% CI: 1.00-17.18), and inadequate initial injections (OR = 7.69, 95% CI: 1.71 34.59) were independently associated with immunoprophylaxis failure. Adequate titers of antibody to HBsAg (anti-HBs, >=100 mIU/mL) were present in 96.5% of immunoprophylaxis-successful infants. For full-term infants, birth weights <3000 g were correlated with low immune responses to vaccination.This improved immunoprophylaxis protocol is effective in preventing perinatal transmission of HBV. Among infants with HBeAg-positive mothers, high HBV viral loads and inadequate and delayed initial injections were associated with immunoprophylaxis failure. The majority of the infants in our study produced adequate levels of protective anti-HBs titers after immunoprophylaxis. Additional efforts to further reduce perinatal transmission should be considered, especially for HBeAg-positive mothers. PMID- 27559948 TI - Harmful effect of epinephrine on postreperfusion syndrome in an elderly liver transplantation recipient with sigmoid ventricular septum: A case report. AB - INTRODUCTION: As a common morphological change of aging heart, sigmoid ventricular septum is frequently found during routine preoperative evaluation, but often disregarded because of its little clinical importance. However, in this report, we describe a 70-year old patient with sigmoid ventricular septum who developed severe hemodynamic deterioration during liver transplantation because of its unique morphology of heart. METHODS: During the course of reperfusion of the graft, patient's hemodynamics were closely monitored using transesophageal echocardiography. RESULTS: Immediately after graft reperfusion, epinephrine was given as a treatment of choice for postreperfusion syndrome. Surprisingly, however, hemodynamic derangement persisted and became even worse. Intraoperative transesophageal echocardiography revealed left ventricular outflow tract obstruction resulting from systolic anterior motion of the mitral valve leaflet. Therefore, the patient was treated with phenylephrine and fluid bolus under the guidance of transesophageal echocardiography. CONCLUSION: As more elderly recipient present for liver transplantation surgery nowadays, left ventricular outflow tract obstruction should always be considered as a possible cause for hemodynamic instability during reperfusion period. In addition, transesophageal echocardiography is a useful tool for both diagnosis of hemodynamic derangement and guidance for appropriate management during liver transplantation surgery. PMID- 27559949 TI - Quantitative hepatitis B core antibody level is associated with inflammatory activity in treatment-naive chronic hepatitis B patients. AB - Previous studies have shown that hepatitis B core antibody (anti-HBc) levels vary during different phases of disease in treatment-naive chronic hepatitis B (CHB) patients and can be used as a predictor of both interferon-alpha and nucleoside analogue therapy response. However, there is no information on the association between the quantitative serum anti-HBc (qAnti-HBc) level and liver inflammation in CHB patients. Therefore, we investigated these relationships in a large cohort of treatment-naive CHB patients. A total of 624 treatment-naive CHB patients were included in the study. The serum qAnti-HBc level was moderately correlated with ALT and AST levels (P < 0.001) in both hepatitis B e antigen-positive (HBeAg [+]) and HBeAg-negative (HBeAg [-]) CHB patients. CHB patients with no to mild inflammation (G0-1) had significantly lower serum qAnti-HBc levels than patients with moderate to severe inflammation (G2-4) (P < 0.001). Receiver operating characteristic analysis suggested that a serum qAnti-HBc cut-off value of 4.36 log10 IU/mL provided a sensitivity of 71.68%, specificity of 73.81%, positive predictive value of 78.43%, and negative predictive value of 66.24% in HBeAg (+) CHB patients with moderate to severe inflammation (G>=2). A cut-off value of 4.62 log10 IU/mL provided a sensitivity of 54.29%, specificity of 90.00%, positive predictive value of 95.00%, and negative predictive value of 36.00% in HBeAg (-) CHB patients with moderate to severe inflammation (G>=2). Serum qAnti-HBc levels were positively associated with liver inflammation grade. Furthermore, we identified optimal serum qAnti-HBc cut-off values for the prediction of inflammation activity in both HBeAg (+) and HBeAg (-) treatment-naive CHB patients. PMID- 27559950 TI - The effect of neck-specific exercise with or without a behavioral approach on psychological factors in chronic whiplash-associated disorders: A randomized controlled trial with a 2-year follow-up. AB - BACKGROUND: To investigate the effect of neck-specific exercise with (NSEB) or without (NSE) a behavioural approach and prescribed physical activity (PPA) on general pain disability and psychological factors in chronic whiplash-associated disorders (WAD), grade 2 and 3, with a 2-year follow-up. METHODS: A randomized controlled multi-centre study of 3 exercise interventions (NSE, NSEB or PPA) including a 2-year follow-up. A total of 216 volunteers with chronic WAD were recruited and 194 were analyzed, mean age 40.4 (Standard Deviation [SD] 11.4). Measures of general pain disability, pain catastrophizing, anxiety and depression, and kinesiophobia were evaluated at baseline, and 3, 6, 12 and 24 months with linear mixed models. RESULTS: General pain disability decreased by 28% in the NSEB group from baseline to 3 months (P < 0.001) and the improvements in disability were maintained over time (6, 12 and 24 months P < 0.01) compared to the NSE (P > 0.42) and PPA groups (P > 0.43). Pain catastrophizing decreased in the NSE group from baseline to 6 and 12 months (P < 0.01) and in the NSEB group from baseline to 3 and 24 months (P < 0.01) compared to the PPA group (P > 0.82) that showed no change over time. The NSE group improved in kinesiophobia over time from baseline to12 months (P < 0.01) compared to the NSEB (P = 0.052) and the PPA groups (P > 0.74). Anxiety decreased over time from baseline to 12 and 24 months in the NSE group (P > 0.02), but not in the NSEB (P > 0.25) or the PPA (P > 0.50) groups. The PPA had no effect on general disability or any of the measured psychological factors. CONCLUSION: This randomised controlled trial with a 2-year follow-up shows that physiotherapist-led neck-specific exercise with or without the addition of a behavioural approach had superior outcome on general disability and most psychological factors compared to the mere prescription of physical activity. PMID- 27559951 TI - Risk of anxiety and depressive disorders in patients with myocardial infarction: A nationwide population-based cohort study. AB - Anxiety and depressive symptoms are associated with adverse cardiovascular events after an acute myocardial infarction (MI). However, most studies focusing on anxiety or depression have used rating scales or self-report methods rather than clinical diagnosis. This study aimed to investigate the association between psychiatrist-diagnosed psychiatric disorders and cardiovascular prognosis.We sampled data from the National Health Insurance Research Database; 1396 patients with MI were recruited as the study cohort and 13,960 patients without MI were recruited as the comparison cohort. Cox proportional hazard regression models were used to examine the effect of MI on the risk of anxiety and depressive disorders.During the first 2 years of follow-up, patients with MI exhibited a significantly higher risk of anxiety disorders (adjusted hazard ratio [HR] = 5.06, 95% confidence interval [CI]: 4.61-5.54) and depressive disorders (adjusted HR = 7.23, 95% CI: 4.88-10.88) than those without MI did. Greater risk for anxiety and depressive disorders was observed among women and patients aged 45 to 64 years following an acute MI. Patients with post-MI anxiety had a 9.37-fold (95% CI: 4.45-19.70) higher risk of recurrent MI than those without MI did after adjustment for age, sex, socioeconomic status, and comorbidities.This nationwide population-based cohort study provides evidence that MI increases the risk of anxiety and depressive disorders during the first 2 years post-MI, and post-MI anxiety disorders are associated with a higher risk of recurrent MI. PMID- 27559952 TI - Transseptal puncture by CTP-2 method: Results from cardiac computed tomography analysis and clinical application. AB - The current used parameters for transseptal puncture (TSP) under fluoroscopic guidance is from left atriography and need to be verified by precise anatomic measurement. From February 2009 to July 2013, consecutive patients who received computed tomography (CT) were included. Landmarks and parameters were preliminary studied by right atriography, and further evaluated on the CT images of 1001 patients. A method (CTP-2) was proposed for guiding TSP. In right anterior oblique 45 degrees view, the CTP-2 method was defined by points C, T, and P, and 2 areas: point C is in coronary sinus; point T is at a distance of dCT (usually 1.5 +/- 0.2 vertebral height) over point C; then point P, the optimal puncture site, was located at 0.5 +/- 0.2 vertebral body height posterior to point T; puncture should avoid the aortic root area and the rear triangle area; the aortic root area could be negatively revealed by right atriography at the orifice of inferior vena cava, and the rear triangle area is demarcated by points C, C', and T' (C' and T' are 2 points horizontally posterior to, and at dCT away from points C and T, respectively). The initial application of CTP-2 in 2820 patients showed that it might be helpful in reducing the need of left atriography and the possibility of cardiac perforation. PMID- 27559954 TI - Reliability of functional gait assessment in patients with Parkinson disease: Interrater and intrarater reliability and internal consistency. AB - To determine the reliability of the functional gait assessment (FGA) as a measure of balance and gait in patients with Parkinson disease (PD).This study involved121 inpatients with PD (mean age 61.9 years). The participants were scored using the FGA by 2 raters, and the testing procedure was videotaped. One of the raters re-assessed the same FGA test via review of the videotaped test 4 weeks later.The interrater and intrarater reliability of the total FGA score was found to be excellent, with an intraclass correlation coefficient of 0.99. The reliability of single items of the FGA ranged from 0.49 to 0.99. The internal consistency of the FGA scores was 0.94.The FGA has high inter-rater and intrarater reliability, and internal consistency for evaluating balance and gait disorders in patients with PD. PMID- 27559953 TI - Early predictive factors for lower-extremity motor or sensory deficits and surgical results of patients with spinal tuberculosis: A retrospective study of 329 patients. AB - Many studies about the characteristics of spinal tuberculosis (STB) have been published, but none has investigated the predictive factors for lower-extremity motor or sensory deficits (LMSD) in patients with STB.The objective of this study was to find early predictive factors for LMSD and evaluate surgical results of patients with STB.From 2001 through 2010, 329 patients with STB were treated in our department and surgical treatment was performed in 274 patients. The factors assessed included age, sex, duration of symptoms, worsening of illness, clinical symptoms, clinical signs, imaging characteristics, kyphotic angle, Oswestry disability index (ODI), and visual analogue scale (VAS) scores.Of the 329 patients studied, 164 presented with LMSD (the LMSD group), of which 93 patients (28.3%) had motor deficits and 177 patients (53.8%) had sensory disturbance. The other 165 patients were included in the control group (the No LMSD group). Using univariate logistic regression analysis, we found that the sex (P = 0.042), age (P = 0.001), worsening of sickness (P = 0.013), location (P = 0.009), and spinal compression (P = 0.035) were the risk factors of LMSD. Furthermore, the multivariate logistic regression analysis indicated that age (OR = 1.761, 95% CI: 1.227-2.526, P = 0.002), worsening of sickness (yes vs no: OR = 1.910, 95% CI: 1.161-3.141, P = 0.011), location (T vs C: OR = 0.204, 95% CI: 0.063-0.662, P = 0.008), and spinal compression (yes vs no: OR = 1.672, 95% CI: 1.020-2.741, P = 0.042) were independent risk factors of LMSD. Surgical treatment was performed in 274 patients. The kyphotic angle improved from 25.8 +/- 9.1 degrees preoperatively to 14.0 +/- 7.6 degrees , with a mean correction of 11.8 +/- 4.0 degrees , and a mean correction loss of 1.5 +/- 1.8 degrees at final visit. There were significant differences between the preoperative and the final ODI and VAS scores in both groups (P < 0.001 and P < 0.001, respectively).Spinal tuberculosis with cervical or lumbar vertebra involvement among the elder patients with a history of worsening of illness and spinal compression tended to cause LMSD, such as motor deficits or sensory disturbance. We should implement an appropriate treatment regimen to prevent exacerbation of STB such as operation, which can achieve thoroughness of debridement, adequate spinal stabilization, and better functional recovery. PMID- 27559955 TI - Changes in ideal cardiovascular health status and risk of new-onset type 2 diabetes: The Kailuan prospective study. AB - The aim of the present study was to investigate the association between the altered ideal cardiovascular health status (DeltaCHS) and the risk of developing diabetes mellitus in the Kailuan population of China.We included 50,656 Chinese adults aged 18 years or older (11,704 men and 38,952 women) without baseline diabetes mellitus in this study. Information about 7 individual components of the cardiovascular health metrics during 2006 to 2008 was collected. A DeltaCHS score was defined as the changes of ideal cardiovascular health status (CHS) from the year 2006 to 2008. New-onset diabetes was identified based on the history of diabetes, currently treated with insulin or oral hypoglycemic agents, or having a fasting blood glucose concentration >=7.0 mmol/L during the 2010 to 2011 and 2012 to 2013 surveys. After a mean follow-up period of 3.80 years, a total of 3071 (6.06%) participants developed diabetes mellitus. Cox proportional hazards regression was used to calculate the hazard ratios and 95% confidence intervals for the CHS change and new-onset diabetes.A strong inverse association between the positive CHS changes and lower risks of developing diabetes mellitus was observed. After adjusting for age, sex, alcohol consumption, and other potential confounders, the hazard ratios for new-onset diabetes were 0.73, 0.59, 0.49, and 0.42 (95% confidence interval: 0.37-0.82; P trend <0.001) for those who met DeltaCHS = -1, 0, 1, and >=2, respectively, compared with the participants with DeltaCHS <=-2.The study concluded that the improved CHS was associated with the reduced risk of developing diabetes mellitus in this investigated Chinese population. PMID- 27559956 TI - Small-arc volumetric-modulated arc therapy: A new approach that is superior to fixed-field IMRT in optimizing dosimetric and treatment-relevant parameters for patients undergoing whole-breast irradiation following breast-conserving surgery. AB - Volumetric-modulated arc therapy (VMAT) is considered to deliver a better dose distribution and to shorten treatment time. There is a lack of research regarding breast irradiation after breast-conserving surgery (BCS) using VMAT with prone positioning. We developed a new small-arc VMAT methodology and compared it to conventional (fixed-field) intensity-modulated radiation therapy (IMRT) in the dosimetric and treatment relevant parameters for breast cancer patients in the prone position.Ten early-stage breast cancer patients were included in this exploratory study. All patients underwent computed tomography (CT) simulation scan in the prone position and for each patient, IMRT and VMAT plans were generated using the Monaco planning system. Two symmetrical partial arcs were applied in the VMAT plans. The angle ranges of the 2 arcs were set to approximately 60 degrees to 100 degrees and 220 degrees to 260 degrees , with small adjustments to maximize target coverage, while minimizing lung and heart exposure. The IMRT plans used 4 fixed fields. Prescribed doses were 50 Gy in 25 fractions. The target coverage, homogeneity, conformity, dose to organs at risk (OAR), treatment time, and monitor units (MU) were evaluated.Higher median conformal index (CI) and lower homogeneity index (HI) of the planning target volume (PTV) were respectively observed in VMAT and plans group (CI, 95% vs 91%; HI, 0.09 vs 0.12; P < 0.001). The volumes of ipsilateral lung receiving 30, 20, 10, and 5 Gy were lower for VMAT (P < 0.01), being 10%, 14.9%, 25.9%, and 44.9%, respectively, compared to 11.79%, 17.32%, 30.27%, and 50.58% for the IMRT plans. The mean lung dose was also reduced from 10.6 +/- 1.8 to 9.6 +/- 1.4 Gy (P = 0.001). The volumes of the heart receiving 30 and 40 Gy were similar for the 2 methods. In addition, the median treatment time (161 vs 412 seconds; P < 0.001) and the mean MU (713 vs 878; P < 0.001) were lower for VMAT.Small-arc VMAT plan improved CI and HI for the target, spared the dose of lung, and reduced treatment time and MU, compared to IMRT. It is a more promising irradiation technique for post-BCS radiotherapy. PMID- 27559957 TI - The prevalence of carotid plaque with different stability and its association with metabolic syndrome in China: The Asymptomatic Polyvascular Abnormalities Community study. AB - Few studies have investigated the prevalence of carotid plaque with different stability in Chinese. As is well known, carotid atherosclerosis is tightly associated with metabolic syndrome (MetS); however, the data about the association between the presence of carotid plaque with different stability and MetS was limited. The aim of our study was to investigate the prevalence of carotid plaque with different stability and its potential association with MetS in general Chinese population.The Asymptomatic Polyvascular Abnormalities Community study is a community-based study to investigate the epidemiology of asymptomatic polyvascular abnormalities in Chinese adults. A total of 5393 participants were finally eligible and included in this study. The carotid plaque and its stability were assessed using ultrasonography. The MetS was defined using the criteria from US National Cholesterol Education Program-Adult Treatment Panel III. Data were analyzed with multivariate logistic regression models.Of the 5393 subjects, 1397 (25.9%) participants had stable carotid plaque, 1518 (28.1%) had unstable carotid plaque in participants, and 1456 (27.0%) had a MetS. MetS was, respectively, significantly associated with the prevalence of carotid plaque (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.07, 1.47), stable carotid plaque (OR: 1.23; 95% CI: 1.02,1.48), and unstable carotid plaque (OR: 1.27; 95% CI: 1.03,1.56) after adjusting for age, gender, level of education, income, smoking, drinking, physical activity, body mass index, low-density lipoprotein, and high-sensitivity C-reactive protein. With the number of MetS components, the prevalence of carotid plaque, stable carotid plaque, and unstable carotid plaque significantly increased (P for trend <0.0001), respectively.In summary, the prevalence of carotid plaque was 54.1%, stable carotid plaque was 25.9%, and unstable carotid plaque was 28.1%. Our study revealed that the prevalence of carotid plaque, stable carotid plaque, and unstable carotid plaque was, respectively, significantly associated with MetS in the general population. PMID- 27559958 TI - Detection of a primary tumor in the area of the renal artery with 18F-FDG PET/CT in a patient with metastatic undifferentiated sarcoma and a history of mid-aortic syndrome: A case report. AB - BACKGROUND: We present a case of a 57-year-old woman patient with a history of mid-aortic syndrome, treated with several vascular procedures, who was referred for investigation of metastatic disease of an undifferentiated sarcoma of unknown origin. METHODS: Positron emission tomography/computed tomography (PET/CT) demonstrated multiple fluorodeoxyglucose (F-FDG) avid lung, liver, and osseous metastases as well as a focus of increased F-FDG uptake in the area of the stented left renal artery. RESULT: Histologic evaluation of soft tissue from the region of the left renal artery revealed atypical spindle cells, consistent with an intimal sarcoma, and with histopathological characteristics identical to those of lung metastases, indicating the F-FDG avid lesion in the area of the renal artery as the origin of the metastatic disease. CONCLUSION: This case highlights the capacity of F-FDG PET/CT to detect primary tumors even of small size and in unusual localisations. Moreover, it provides further indications regarding the potential association between foreign body reaction on the basis of chronic inflammation and sarcoma development. PMID- 27559959 TI - An uncommon case of lymphoplasmacytic lymphoma in cerebellopontine angle region: Case report with a literature review. AB - In the central nervous system, cerebellopontine angle (CPA) lymphomas are rare; few cases have been reported. Lymphoplasmacytic lymphoma (LPL) in the CPA is rarer still, and often misdiagnosed as acoustic neuroma.We report a rare case of CPA LPL-a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological test.A 43-year-old woman presented with headaches. Her magnetic resonance imaging revealed an abnormal homogeneously enhancing mass in the left CPA. We present detailed analysis of her disease and review relevant literature.When surgically treated, her specimen showed a typical LPL histopathology pattern. After surgery, the patient's symptoms improved greatly, and she received chemotherapy.Despite its rarity, LPL should be considered in differential diagnoses of CPA lesions that mimic acoustic neuromas. PMID- 27559960 TI - Differences in pregnancy outcomes, prenatal care utilization, and maternal complications between teenagers and adult women in Korea: A nationwide epidemiological study. AB - Teenage mothers are at high risk for maternal and neonatal complications. This study aimed to evaluate the socioeconomic circumstances of teenage pregnancy, and determine whether these increased risks remained after adjustment for socioeconomic circumstances in Korea. Using the National Health Insurance Corporation database, we selected women who terminated pregnancy, by delivery or abortion, from January 1, 2010 to December 31, 2010. Abortion, delivery type, and maternal complications were defined based on the International Classification of Diseases-10th Revision. We compared teenagers (13-19 years at the time of pregnancy termination) with other age groups and investigated differences based on socioeconomic status, reflected by Medical Aid (MA) and National Health Insurance (NHI) beneficiaries. We used multivariate analysis to define the factors associated with preterm delivery. Among 463,847 pregnancies, 2267 (0.49%) involved teenagers. Teenage mothers were more likely to have an abortion (33.4%) than deliver a baby when compared with other age groups (20.8%; P < 0.001). About 14.4% of teenage mothers had never received prenatal care throughout pregnancy. Among teenage mothers, 61.7% of MA recipients made fewer than 4 prenatal care visits (vs 38.8% of NHI beneficiaries) (P < 0.001). Teenage mothers more often experienced preterm delivery and perineal laceration (P < 0.001). Teenage mothers (<20 years) were 2.47 times more likely to have preterm delivery than older mothers (20-34 years; P < 0.001). Teenage mothers had higher risk of inadequate prenatal care and subsequently of preterm delivery, which remained significantly higher after adjusting for socioeconomic confounding variables and adequacy of prenatal care in Korean teenagers (P < 0.001). PMID- 27559961 TI - Prevalence and risk factors for efavirenz-based antiretroviral treatment associated severe vitamin D deficiency: A prospective cohort study. AB - Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD.Treatment-naive Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV coinfected patients, rifampicin-based anti-TB treatment was initiated 4 or 8 weeks before starting cART. Plasma 25 hydroxyvitamin D (25 [OH]D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, 4, 16, and 48 week of cART. Plasma efavirenz concentrations were determined at 4 and 16 weeks of cART.TB-HIV patients had significantly lower plasma 25 (OH)D3 levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load, and high CYP3A activity as measured by plasma 4beta-hydroxycholesterol/cholesterol ratios were significant predictors of low 25 (OH)D3 levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79%, and 43% at 4, 16, and 48 weeks of cART, respectively. The median 25 (OH)D3 levels declined from baseline by -40%, -50%, and -14% at 4, 16, and 48 weeks of cART, respectively.In TB-HIV patients, previous anti-TB therapy had no influence on 25 (OH)D3 levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at the 4 and 16 weeks of cART, respectively. Median plasma 25 (OH)D3 declined from baseline by -17% and -21% at week 4 and 16 of cART, respectively.Our results indicate low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations as significant predictors of early efavirenz-based cART-induced vitamin D deficiency. Low plasma 25 (OH)D3 level at baseline is associated with TB co-infection and HIV diseases progression. Initiation of efavirenz-based cART is associated with high incidence of SVDD, whereas rifampicin based anti-TB therapy co-treatment has no significant effect. Supplementary vitamin D during cART initiation may be beneficial for HIV patients regardless of TB coinfection. PMID- 27559962 TI - Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: A case report and review of the literature. AB - BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD. Recent reports, however, have raised the possibility that some patients with IgG4-RD are ANCA positive, thus suggesting reconsideration of the role of ANCA in the diagnostic workup. In the present work, we describe the first case of concomitant biopsy-proven IgG4-RD and granulomatosis with polyangiitis (GPA), demonstrating antiproteinase 3 (PR3) ANCA of the IgG4 subclass in the patient's serum. We also review the literature in order to provide clinicians with tools for interpreting ANCA positivity in IgG4-RD patients. CASE SUMMARY: A 51-year-old woman was referred for left exopthalmos due to lacrimal gland enlargement and increased serum IgG4 concentration. IgG4-RD was suspected and further imaging studies disclosed multiple pulmonary masses in the right lung. Histological analysis of the left lacrimal gland was diagnostic for IgG4-RD, but lung biopsy showed typical features of GPA. ANCA assay was positive for anti-PR3 antibodies. Further immunofluorescence studies demonstrated anti-PR3 antibodies of IgG1 and IgG4 subclass. Treatment with rituximab induced swift remission of both IgG4-RD and GPA manifestations. We identified 9 other reports of patients with IgG4-RD and positive ANCA in the English literature, 5 cases with biopsy-proven IgG4-RD and 4 cases in whom IgG4-RD was diagnosed presumptively. Four patients had also histological evidence of concomitant AAV. CONCLUSION: The present work demonstrates that ANCA positivity in patients with biopsy-proven IgG4-RD should prompt the exclusion of a concomitant vasculitic process; a positive ANCA does not exclude the diagnosis of IgG4-RD; confirmation through immunoenzymatic assays of the ANCA specificity, clinical-pathological correlation, and histopathological evaluation remain crucial steps for the differential diagnosis between AAV and IgG4-RD. PMID- 27559963 TI - Horizontal eyeball akinesia as an initial manifestation of CLIPPERS: Case report and review of literature. AB - BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare chronic inflammatory disorder in the central nervous system (CNS), which is characterized by magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement "peppering" the pons. Lesions of CLIPPERS mainly involve the pons and the cerebellum. Adjacent structures such as the medulla and the midbrain may also be involved. It is proposed that CLIPPERS is an immune-mediated inflammatory condition characteristic of T-cell-predominant infiltrates and good responsiveness to corticosteroids. METHODS AND RESULTS: We report a 46-year-old woman who presented with horizontal eyeball akinesia and gait ataxia with characteristic MRI features of CLIPPERS. The possible pathogenesis, clinical manifestations, imaging features, treatment, and prognosis of this peculiar disorder are summarized. CONCLUSION: This report contributes to the clinical understanding of CLIPPERS which may present with horizontal eyeball akinesia as an initial manifestation. The characteristic presentation of a subacute cerebellar and brainstem syndrome and pepper-like gadolinium enhancement was confirmed in this report. Long-term immunosuppressive treatment seems to be mandatory to sustain improvement. Azathioprine alone may be capable of maintaining remission. PMID- 27559964 TI - Feasibility of body roundness index for identifying a clustering of cardiometabolic abnormalities compared to BMI, waist circumference and other anthropometric indices: the China Health and Nutrition Survey, 2008 to 2009. AB - The body mass index (BMI) and waist circumference (WC) are commonly used anthropometric measures for predicting cardiovascular diseases risk factors, but it is uncertain which specific measure might be the most appropriate predictor of a cluster of cardiometabolic abnormalities (CMA) in Chinese adults. A body shape index (ABSI) and body roundness index (BRI) have been recently developed as alternative anthropometric indices that may better reflect health status. The main aims of this study were to investigate the predictive capacity of ABSI and BRI in identifying various CMA compared to BMI, WC, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), and to determine whether there exists a best single predictor of all CMA.We used data from the 2009 wave of the China Health and Nutrition Survey, and the final analysis included 8126 adults aged 18 to 85 years with available fasting blood samples and anthropometric measurements. Receiver-operating characteristic (ROC) analyses were conducted to assess the best anthropometric indices to predict the risk of hypertension, diabetes, dyslipidemia, hyperuricemia, and metabolic syndrome (MetS). Logistic regression models were fit to evaluate the OR of each CMA according to anthropometric indices.In women, the ROC analysis showed that BRI and WHtR had the best predictive capability in identifying all of CMA (area under the curves [AUCs] ranged from 0.658 to 0.721). In men, BRI and WHtR were better predictor of hypertension, diabetes, and at least 1 CMA (AUC: 0.668, 0.708, and 0.698, respectively), whereas BMI and WC were more sensitive predictor of dyslipidemia, hyperuricemia, and MetS. Furthermore, the ABSI showed the lowest AUCs for each CMA. According to the multivariate logistic regression analysis, BRI and WHtR were superior in discriminating hyperuricemia and at least 1 CMA while BMI performed better in predicting hypertension, diabetes, and MetS in women. In men, WC and BRI were the 2 best predictor of all CMA except MetS, and the ABSI was the worst.Our results showed the novel index BRI could be used as a single suitable anthropometric measure in simultaneously identifying a cluster of CMA compared to BMI and WHtR, especially in Chinese women, whereas the ABSI showed the weakest discriminative power. PMID- 27559965 TI - Sinonasal oncocytic Schneiderian papilloma accompanied by intravascular lymphoma: A case report on FDG-PET/CT imaging. AB - INTRODUCTION: F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful for the staging and assessment of treatment response in patients with lymphoma. Occasionally, benign lesions demonstrate avid FDG uptake and result in false positive findings. CASE: We report the case of an 82-year-old man presenting with cutaneous lesions, which were histopathologically diagnosed as intravascular lymphoma. FDG-PET/CT for staging demonstrated an FDG avid mass extending from the right maxillary sinus to the nasal cavity, moderate uptake in the adrenal glands, mild uptake in the knee and the foot, and faint uptake in the skin and subcutaneous tissue of the legs. He subsequently underwent biopsy of the paranasal mass, which was diagnosed as oncocytic Schneiderian papilloma without lymphoma invasion. Glucose transporter (GLUT) 1 staining was highly positive in the papilloma cells, resulting in high FDG avidity. After completion of chemotherapy, the abnormal FDG uptakes in the skin, soft tissue, and adrenal glands disappeared on PET/CT. However, avid FDG uptake persisted in the sinonasal Schneiderian papilloma for 15 months before regression. CONCLUSION: Benign tumors with oncocytic components may show avid FDG uptake. Therefore, correct diagnosis of oncocytic Schneiderian papilloma on FDG images is difficult when other accompanying malignant tumors, especially lymphoma, are present. If post-therapeutic PET/CT images show a discordant lesion, oncocytic tumors, albeit uncommon, should be considered in the differential diagnoses. PMID- 27559966 TI - Minimum effective local anesthetic volume for surgical anesthesia by subparaneural, ultrasound-guided popliteal sciatic nerve block: A prospective dose-finding study. AB - Because of its rapid onset time, recent years have seen an increase in the use of ultrasound (US)-guided popliteal sciatic nerve block (PSNB) via subparaneural injection for induction of surgical anesthesia. Moreover, in below-knee surgery, combined blocks, as opposed to sciatic nerve block alone, have become more common. These combined blocks often require a large volume of local anesthetic (LA), thus increasing the risk of local-anesthetic systemic toxicity (LAST). Thus, to decrease the risk of LAST, it is important to know the minimum effective volume (MEV) required for an adequate block. We, therefore, aimed to determine the MEV of ropivacaine 0.75% for induction of surgical anesthesia by the method of US-guided popliteal sciatic nerve block via subparaneural injection.Thirty patients underwent a US-guided PSNB with ropivacaine 0.75% at a 20-mL starting volume. Using a step-up/step-down method, we determined injection volumes for consecutive patients from the preceding patient's outcome. When an effective block was achieved within 40 minutes after injection, the next patient's volume was decreased by 2 mL. If the block failed, the next patient's volume was increased by 2 mL. The sensory and motor blockade was graded according to a 4 point scale. The block was considered a success if a combination of anesthesia and paresis (a score of 3 for both the sensory and motor nerves) was achieved within 40 minutes. The primary outcome measure was the MEV resulting in a successful subparaneural block of the sciatic nerve in 50% of patients (MEV50). Additionally, the data were processed with a probit regression analysis to determine the volume required to produce a complete sciatic nerve block in 90% of subjects (ED90).The MEV50 of 0.75% ropivacaine is 6.14 mL (95% confidence interval, 4.33-7.94 mL). The ED90 by probit analysis for a subparaneural injection was 8.9 mL (95% CI, 7.09-21.75 mL).The 6.14-mL MEV50 of ropivacaine 0.75% represents a 71% reduction in volume compared with neurostimulation techniques and a 14.7% reduction in volume compared with US-guided PSNB using the alternative perineural injection technique. PMID- 27559967 TI - Gray matter increases in fronto-parietal regions of depression patients with aripiprazole monotherapy: An exploratory study. AB - We investigated the treatment effects of aripiprazole monotherapy in first episode medication-naive patients with major depressive disorder (MDD). The accompanying changes in the gray matter volume (GMV) were also explored.Fifteen patients completed the trial and received structural scans by 3-Tesla magnetic resonance imaging at baseline and partially responding state (sixth week). To account for the test-retest bias, 27 healthy controls were scanned twice within 6 weeks. We utilized optimized voxel-based morphometry with different comparisons between groups.The partially responding patients with MDD had greater GMV in left middle frontal gyrus and left superior parietal gyrus when compared with baseline. However, they had decreases in the GMV of right orbitofrontal gyrus and right inferior temporal gyrus after response. The partially responding patients with MDD still had residual GMV deficits in right superior frontal gyrus when compared with controls. However, the lack of second patient group without aripiprazole intervention would be a significant limitation to interpret the aripiprazole-specific effects on GMV.The changes in the GMV of fronto-parieto temporal regions and residual GMV deficits in the superior frontal gyrus might represent "state-dependent brain changes" and "residual-deficit brain regions," respectively, for aripiprzole monotherapy in MDD. PMID- 27559968 TI - Radiofrequency ablation for treatment of benign thyroid nodules: A PRISMA compliant systematic review and meta-analysis of outcomes. AB - BACKGROUND: Thyroid nodules (TNs) usually appearing in the general population have the potential possibility of malignant transformation and common problems of jugular oppression such as dyspnea and hoarseness. We performed this meta analysis to evaluate the efficiency of radiofrequency ablation (RFA) for the treatment of benign TNs in accord with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements. METHODS: Published literatures were retrieved from PubMed, Embase, Web of Science, and Scopus up to January 27, 2016. Pooled standard mean difference with 95% confidence interval was estimated by fixed- or random-effects model depending on heterogeneity, which was calculated using the Cochran Q, tau, and I statistics. The quality of the articles was evaluated by the Newcastle-Ottawa scale. RESULTS: Meta-analysis of data from 1090 patients with 1406 benign TNs in 20 articles showed that with the subgroup stratified by nodule volume, they were significantly decreased at 1, 3, 6, 12, and the last follow-up months, when comparing post-RFA with the initial nodule volume. In addition, the volume also notably declined by cold and hot nodules. By subgrouping into the largest diameter, symptom score, cosmetic score, thyrotropin, triiodothyronine, free thyroxine level, and vascularity, the pooled data indicated that there was a decrease in largest diameter, symptom score, cosmetic score, triiodothyronine level, and vascular scale, an unchanged free thyroxine, and an increased thyrotropin level after RFA. The publication bias for this particular study is presented in the following groups: nodule volume reduction at 6 months and last follow-up month after RFA and symptom score. CONCLUSION: In summary, by pooling of these studies we recommended that RFA indeed has the advantages in improving outcomes and providing better prognosis for patients with benign TNs. PMID- 27559969 TI - Personal mastery attenuates the adverse effect of frailty on declines in physical function of older people: A 6-year population-based cohort study. AB - Personal mastery is an important determinant in shaping physical health across middle and late life. The modified effect of mastery on relation between frailty and adverse health outcome remains unclear. The main purpose of this study was to evaluate the prognostic role of mastery on frailty among older people by using a nationwide representative population-based cohort. In total, 715 community dwelling participants aged 54 years and over recruited in 2000 and received second visit 6 years later. Personal mastery was represented by the Pearlin mastery score, and frailty was defined by modified Fried criteria. Multivariate generalized linear mixed analysis was used to examine the association interaction between frailty and Pearlin mastery scores for activities of daily living decline. Overall, prevalence of frailty and prefrail were 9.7% and 48.8%. In a 6 year period, 94 participants (13.1%) experienced functional decline. Compared with function nondecliners, function decliners had greater proportion of frailty (26.6% vs 7.1%; P < 0.001) and lesser mastery score (17.2 vs 18.7; P < 0.001). After adjusting with basic demography, healthy behavior, cognitive function, and multimorbidity, frailty status and mastery were significantly interacted (coefficient estimate: -0.80, standard error: 0.23, P = 0.001). The negative coefficient estimate indicated that self-control, that is, self-mastery, may attenuate the adverse effects of frailty on functional outcomes. Similar results were shown when subjects with baseline functional deficits were excluded for analysis. In conclusion, high self-mastery attenuates adverse effects of frailty on functional decline. PMID- 27559970 TI - Gout increases risk of fracture: A nationwide population-based cohort study. AB - There is still debate on whether high uric acid increases bone mineral density (BMD) against osteoporotic fracture or bone resorption caused by gout inflammation. This study aimed to evaluate whether gout offers a protective effect on bone health or not. We conducted a nationwide population-based retrospective cohort study to evaluate the association between gout history and risk factors of fracture.A retrospective cohort study was designed using the claim data from Longitudinal Health Insurance Database (LHID). A total of 43,647 subjects with gout and a cohort of 87,294 comparison subjects without gout were matched in terms of age and sex between 2001 and 2009, and the data were followed until December 31, 2011. The primary outcome of the study was the fracture incidence, and the impacts of gout on fracture risks were analyzed using the Cox proportional hazards model.After an 11-year follow-up period, 6992 and 11,412 incidents of fracture were reported in gout and comparison cohorts, respectively. The overall incidence rate of fracture in individuals with gout was nearly 23%, which was higher than that in individuals without gout (252 vs 205 per 10,000 person-years) at an adjusted hazard ratio of 1.17 (95% confidence interval = 1.14 1.21). Age, sex, and fracture-associated comorbidities were adjusted accordingly. As for fracture locations, patients with gout were found at significant higher fracture risks for upper/lower limbs and spine fractures. In gout patient, the user of allopurinol or benzbromarone has significantly lower risk of facture than nonusers.Gout history is considered as a risk factor for fractures, particularly in female individuals and fracture sites located at the spine or upper/lower limbs. PMID- 27559971 TI - Do psychological interventions reduce depression in hemodialysis patients?: A meta-analysis of randomized controlled trials following PRISMA. AB - BACKGROUND: Depression is highly prevalent in hemodialysis patients and results in poor patient outcomes. Although psychological interventions are being developed and used for these patients, there is uncertainty regarding the effectiveness of these interventions. The purpose of this meta-analysis is to evaluate the effects of psychological interventions on depression treatment in hemodialysis patients. METHODS: All randomized controlled trials (RCTs) relevant to the depression treatment of hemodialysis patients through psychological interventions were retrieved from the following databases: Embase, Pubmed, PsycINFO, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. The reference lists of identified RCTs were also screened. The Cochrane risk of bias tool was used to evaluate the quality of the studies, RevMan (5.3) was used to analyze the data, and the evidence quality of the combined results was evaluated using GRADE (3.6.1). RESULTS: Eight RCTs were included. The combined results showed that psychological interventions significantly reduced the scores of the Beck Depression Inventory (P<0.001) and interdialysis weight gain (P<0.001). However, due to the high heterogeneity, effect size combinations of sleep quality and quality of life were not performed. CONCLUSION: Psychological interventions may reduce the degree of depression and improve fluid intake restriction adherence. More rigorously designed research is needed. PMID- 27559972 TI - Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients: A systematic review and meta-analysis. AB - BACKGROUND: Previous studies have shown that sugammadex, a modified gamma cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. METHODS: A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I) assessment was performed. RESULTS: Six randomized controlled trials comparing 253 pediatric patients (age range, 2-18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of >=0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were -7.15 (95% CI: -10.77 to -3.54; I = 96%; P = 0.0001) and -17.32 (95% CI: -29.31 to -5.32; I = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was -6.00 (95% CI: 11.46 to -0.53; I = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27-1.71; I = 59%; P = 0.41). CONCLUSION: We suggest that sugammadex is fast and effective in reversing rocuronium-induced NMB in pediatric patients. Although there was no evidence of a higher incidence of adverse events with sugammadex compared to that with neostigmine or placebo, much more data regarding the safety of sugammadex in pediatric patients may be still required. PMID- 27559973 TI - Severe acute hemorrhagic pancreatitis secondary to cholelithiasis as a rare cause of sudden unexpected death in medico-legal case: A case report. AB - INTRODUCTION: Acute pancreatitis (AP) is an uncommon disease with a wide clinical course varying from mild and self-limiting to severe with eventual death. However, death caused by AP is rare. Most cases of AP reported in the English language literature are based on clinical data; few are medico-legal studies. CASE PRESENTATION: The author recently experienced a case of sudden unexpected death in a young man caused by extensive severe hemorrhagic AP secondary to cholelithiasis, not chronic alcoholism, which is a much more prominent etiology of AP in medico-legal perspectives. The deceased had complained of dizziness, nausea, and fatigue without significant abdominal pain for about 1 week and received some home medications for symptomatic treatment including an antibiotic drug from a clinic just 2 days prior to his death. He had complained of lower extremity weakness, intense thirst, and subsequently collapsed and was brought to a nearby hospital where he was pronounced dead shortly after his admission following unsuccessful advanced cardiopulmonary resuscitation attempts. CONCLUSION: This case is herein reported with an extensive review of the pertinent literature to highlight the findings of the case and raise awareness within the medico-legal profession and also the medical profession. PMID- 27559975 TI - A neglected point in surgical treatment of adolescent idiopathic scoliosis: Variations in the number of vertebrae. AB - Inaccurate identification of vertebral levels is the main cause of wrong-site spine surgery which is performed by nearly half of the spine surgeons. Unusual anatomy and failure to verify the surgical level on radiographs have been commonly reported. We aimed at investigating the variations in vertebral number in adolescent idiopathic scoliosis (AIS) patients and thus to raise awareness of the possibility for wrong-level spinal surgery and to make a comparison with normal adolescents. A cohort of 657 AIS patients and 248 normal adolescents, presented to our center from June 2008 to February 2013, who met the inclusion criteria, were recruited. Radiographs were reviewed to identify the number of thoracic or lumbar vertebrae and the presence of a lumbosacral transitional vertebra. In the AIS group, 70 (10.6%) patients had variations in the number of thoracic and/or lumbar vertebrae. Remarkably, the prevalence of variations in male subjects was significantly higher than that in female subjects (P < 0.05). Thirty-seven patients (5.6%) had an atypical number of thoracic vertebrae, with 33 having 11 thoracic vertebrae and 4 patients having 13. Forty-eight patients (7.3%) had an atypical number of lumbar vertebrae, with 14 having 4 lumbar vertebrae and 34 patients having 6. Multilevel vertebral anomalies were present in 2.3% of the patients (15 of 657). A variation in the number of vertebrae had been identified in 1.7% (11) of the reports by the radiologist. In the normal group, 27 (10.9%) subjects showed variations in the vertebral number. There was no significant difference in the prevalence of atypical numbers of vertebral number between the AIS and normal groups (P > 0.05). Therefore, we concluded that variations in the number of thoracic-lumbar vertebrae were found in up to10.6% of AIS patients. Identification of variations in the number of vertebrae is crucial to serve to decrease the risk of wrong-level surgery. PMID- 27559974 TI - Associations between the number of natural teeth and renal dysfunction. AB - The purpose of the present study was to investigate the association between the number of natural teeth and measures of kidney dysfunction, such as urinary albumin/creatinine ratio (ACR) and estimated glomerular filtration (eGFR) rate, using nationally representative data.The data used were from the Korea National Health and Nutrition Examination Survey with cross-sectional design, which was conducted between 2011 and 2012; the sample analyzed in this study consisted of a total of 10,388 respondents, each of whom was 19 years or older and had no missing outcome variables. The association between the number of natural teeth and kidney function was assessed by multiple logistic regression and model was adjusted for age, sex, waist conference, smoking, drinking, exercise, education, income, frequency of tooth brushing per day, diabetes, metabolic syndrome, urinary ACR, and eGFR.The mean age, body mass index, and waist circumference were significantly higher among those with lower kidney function (urinary ACR >=30 mg/g and eGFR <60 mL/min/1.73m). Urinary ACR and eGFR were associated with loss of natural teeth. As urinary ACR increased, the number of natural teeth decreased accordingly. Conversely, the number of natural teeth increased with an increase in eGFR.This study showed that the number of natural teeth is inversely associated with the presence of kidney disease. Severity of tooth loss may be considered an independent risk indicator for kidney disease among Koreans. More epidemiological studies are warranted to investigate the role of tooth loss in kidney disease, to confirm this relationship and to test possible underlying mechanisms. PMID- 27559976 TI - The characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital: A retrospective cohort study. AB - The aim of this cohort study was to determine the characteristics and clinical outcome of 287 patients with drug-induced liver injury (DILI) in a Chinese hospital.Between January 2008 and January 2013, individuals who were diagnosed with DILI were selected. The complete medical records of each case were reviewed, and factors for the outcome of patients with DILI were extracted and analyzed using univariate and multivariate analysis.Two hundred eighty-seven cases identified as DILI were included in the study. A total of 105 different drugs were considered to be related to the hepatotoxicity. The main causative group of drugs was Chinese herb (n = 111). Liver failure developed in 9 (3.1%) patients, and 2 died (0.7%). Overall, complete recovery occurred in 92 (32.1%) patients. Univariate analysis and binary logistic regression analysis identified the digestive symptoms, jaundice, total bilirubin (TBIL), and direct bilirubin (DBIL) as independent factors for the non-recovery of DILI. Then the prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, was built by using binary logistic regression analysis again. Receiver operating characteristic curve validated the strong power (area under the curve (AUC) = 0.907) of prediction model for predicting the DILI non-recovery.DILI is an important cause of liver test abnormalities, and Chinese herb represented the most common drug group. The factors such as digestive symptoms, jaundice, TBIL, and DBIL have effect on DILI outcomes. The prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, established in this study is really an excellent predictive tool for non recovery of DILI patients. PMID- 27559977 TI - Beating-heart surgical treatment of tricuspid valve papillary fibroelastoma: A case report. AB - BACKGROUND: Cardiac papillary fibroelastomas are rare. And only 15% of the papillary fibroelastomas are located on tricuspid valve. However, the treatment of papillary fibroelastomas varies. CASE SUMMARY: We report a 75-year-old Chinese male who was hospitalized because of a right atrial mass found by echocardiography. Complete tumor excision along with Kay's tricuspid valvuloplasty surgery on beating heart under cardiopulmonary bypass was performed to the patient. Pathologic examination confirmed the definite diagnosis of cardiac papillary fibroelastoma. The recovery of the patient was uneventful and echocardiographic examination performed 6 months after surgery revealed no recurrence of the tumor. CONCLUSIONS: Beating-heart surgical excision is an effective and safe treatment of tricuspid papillary fibroelastomas. PMID- 27559978 TI - Safety and feasibility of the RhinoChill immediate transnasal evaporative cooling device during out-of-hospital cardiopulmonary resuscitation: A single-center, observational study. AB - We investigated feasibility and safety of the RhinoChill (RC) transnasal cooling system initiated before achieving a protected airway during cardiopulmonary resuscitation (CPR) in a prehospital setting.In out-of-hospital cardiac arrest (OHCA), transnasal evaporative cooling was initiated during CPR, before a protected airway was established and continued until either the patient was declared dead, standard institutional systemic cooling methods were implemented or cooling supply was empty. Patients were monitored throughout the hypothermia period until either death or hospital discharge. Clinical assessments and relevant adverse events (AEs) were documented over this period of time.In total 21 patients were included. Four were excluded due to user errors or meeting exclusion criteria. Finally, 17 patients (f = 6; mean age 65.5 years, CI95%: 57.7 73.4) were analyzed. Device-related AEs, like epistaxis or nose whitening, occurred in 2 patients. They were mild and had no consequence on the patient's outcome. According to the field reports of the emergency medical services (EMS) personnel, no severe technical problems occurred by using the RC device that led to a delay or the impairment of quality of the CPR.Early application of the RC device, during OHCA is feasible, safe, easy to handle, and does not delay or hinder CPR, or establishment of a secure intubation. For efficacy and further safety data additional studies will be needed. PMID- 27559979 TI - A new multiparameter integrated MELD model for prognosis of HBV-related acute-on chronic liver failure. AB - Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is one of the most deadly diseases. Many models have been proposed to evaluate the prognosis of it. However, these models are still controversial. In this study, we aimed to incorporate some characters into model for end-stage liver disease (MELD) to establish a new reliable and feasible model for the prognosis of HBV-ACLF.A total of 530 HBV-ACLF patients who had received antiviral therapy were enrolled into a retrospective study and divided into the training cohort (300) and validation cohort (230). Logistic regression analysis was used to establish a model to predict the 3-month mortality from the patients in the training cohort, and then, the new model was evaluated in the validation cohort.Except for MELD score, 4 other independent factors, namely degree of hepatic encephalopathy (HE), alpha fetoprotein (AFP), white blood cell (WBC) count, and age, were important for the new model called HBV-ACLF MELD (HAM) model: R = 0.174 * MELD + 1.106 * HE - (0.003 * AFP) + (0.237 * WBC) + (0.103 * Age) - 11.388. The areas under receiver operating characteristic curve of HAM in the training and validation cohort were 0.894 and 0.868, respectively, which were significantly higher than those of other 7 models. With the best cut-off value of -1.191, HAM achieved higher sensitivity and negative predictive value.We developed a new model that has a great prognostic value of the 3-month mortality of patients with HBV-ACLF. PMID- 27559980 TI - Prevalence, awareness, treatment, and control of hypertension and associated risk factors among adults in Xi'an, China: A cross-sectional study. AB - To investigate the prevalence, awareness, treatment, and control of hypertension, and the associated risk factors among adults in Xi'an, China.From October to December 2013, participants in Xi'an, China were recruited for the study by using a multiple-stage sampling method. A self-developed questionnaire with an additional health examination was used to collect data on the history of hypertension diagnosis and antihypertensive medication. The status on prevalence, awareness, treatment, and control of hypertension were analyzed and related risk factors were identified by using logistic regression analysis.A total of 8193 participants were included with an overall prevalence of hypertension of 20.4%. Among the hypertensive participants, 63.7% were aware of their conditions, 47.3% took antihypertensive medication, and 17.8% had their blood pressure (BP) controlled within 140/90 mm Hg. More complications and less frequent BP measurements were associated with hypertension. Older participants, non-drinkers, and those with more complications and more frequent BP measurements were more aware of their hypertension. Being older, living in an urban area, and having more frequent BP measurements were all factors for better treatment. Participants who were women, living in an urban area, with a higher educational level and who were not obese were more likely to have their hypertension controlled.The prevalence of hypertension among adults in Xi'an is high with suboptimal low awareness, treatment, and control rates. Further comprehensive integrated strategies based on these risk factors should be taken into account in order to improve the prevention, awareness, treatment, and control of hypertension. PMID- 27559981 TI - Reduction in postpartum weight with laser acupuncture: A randomized control trial. AB - BACKGROUND: Gestational weight gain and weight retention at 1 year after delivery are associated with long-term obesity. We aimed to investigate the effect of laser acupuncture therapy on postpartum weight control. METHODS: We randomly assigned 66 subjects with postpartum weight retention to a laser acupuncture group and control group. The subjects were treated at acupoints including the stomach and hunger points of the ear, ST25, ST28, ST40, SP15, CV9, and SP6 by using verum or sham laser acupuncture over 5 sessions per week. After 12 treatment sessions, the differences in the body mass index (BMI), body fat percentage (BFP), and waist-to-buttocks ratio (WBR) of the patients were analyzed and compared between the laser acupuncture and control groups via analysis of variance, chi-square tests, and stepwise regression tests. RESULTS: The characteristics of the patients did not significantly differ between the laser acupuncture and control groups. Analysis of repeated measures data between the laser acupuncture and control groups indicated the presence of significant differences in postpartum BMI (P < 0.001) and BFP (P < 0.001); however, no significant difference was observed for WBR (P = 0.09). CONCLUSION: Laser acupuncture reduces postpartum weight retention by improving BMI and BFP, but does not impact the WBR following short-term treatment. PMID- 27559982 TI - Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma: A care-compliant case report. AB - BACKGROUND: Clinically, elderly patients with unresectable bulky hepatocellular carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor control were observed. CASE SUMMARY: At presentation, an 85-year-old male patient complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a 12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA (cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA), trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEB-VMAT technique was given alternatively. RT was delivered in 26 fractions, with dose gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized potential anti HCC agent) was retrospectively found to be prescribed for alleviating skin itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for 24 months).After RT, significant symptoms alleviation and tumor volume reduction were observed for 32 months till multiple bone metastases. Before and after RT, a large tumor volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe treatment toxicity was noted during and after RT. The patient died due to aspiration pneumonia with septic shock at 4 months after bone metastases identified. CONCLUSIONS: SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were observed in this elderly patient with unresectable bulky HCC. Further prospective randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without cyproheptadine. PMID- 27559983 TI - The clinicopathological features and prognostic factors of gastric squamous cell carcinoma. AB - Primary gastric squamous cell carcinoma (SCC) is an exceedingly rare disease. We increased the understanding of gastric SCC and evaluated prognostic factors of gastric SCC.In this large-population cohort study, we retrospectively collected 163 primary gastric SCC and 66,209 primary gastric adenocarcinoma cases from the surveillance, epidemiology, and end results program (SEER) database from 1988 to 2012. The Chi-squared test demonstrated the distributed differences. Cox proportional hazards regression model was used to evaluate the prognostic factors.Gastric SCC accounted for 0.2% of all the primary gastric cancer cases. The mean age of patients with gastric SCC was 69.6 years old, and the man-to woman ratio was 2.3:1. The proportion of black was higher in gastric SCC than gastric adenocarcinoma (P < 0.001). Almost half of the gastric SCCs were diagnosed in stage IV and more than half were poorly differentiated. In gastric SCC, the median survival was 8.0 months and the 5-year overall survival (OS) was 32.7%; in gastric adenocarcinoma the median survival rate was 19.0 months and the 5-year OS was 35.4%. The multivariate analysis showed that number of primary lesions, tumor location, grade, and stage were independent prognostic factors in gastric SCC. The tumor stage was the most important prognostic factor.Primary gastric SCC is exceedingly rare. Compared with gastric adenocarcinoma, gastric SCC was more frequent in black patients and was usually diagnosed when it was poorly differentiated and at a later stage. On the whole, gastric SCC has a poorer outcome. Disease stage is likely a key determinant in survival. PMID- 27559985 TI - Smart Adsorbents with Photoregulated Molecular Gates for Both Selective Adsorption and Efficient Regeneration. AB - Selective adsorption and efficient regeneration are two crucial issues for adsorption processes; unfortunately, only one of them instead of both is favored by traditional adsorbents with fixed pore orifices. Herein, we fabricated a new generation of smart adsorbents through grafting photoresponsive molecules, namely, 4-(3-triethoxysilylpropyl-ureido)azobenzene (AB-TPI), onto pore orifices of the support mesoporous silica. The azobenzene (AB) derivatives serve as the molecular gates of mesopores and are reversibly opened and closed upon light irradiation. Irradiation with visible light (450 nm) causes AB molecules to isomerize from cis to trans configuration, and the molecular gates are closed. It is easy for smaller adsorbates to enter while difficult for the larger ones, and the selective adsorption is consequently facilitated. Upon irradiation with UV light (365 nm), the AB molecules are transformed from trans to cis isomers, promoting the desorption of adsorbates due to the opened molecular gates. The present smart adsorbents can consequently benefit not only selective adsorption but also efficient desorption, which are exceedingly desirable for adsorptive separation but impossible for traditional adsorbents with fixed pore orifices. PMID- 27559986 TI - Fabrication of metallic nanodisc hexagonal arrays using nanosphere lithography and two-step lift-off. AB - Nanosphere lithography (NSL) has been widely used as an inexpensive method to create periodic arrays of metallic nanoparticles or nanodiscs on substrates. However, most nanodisc arrays derived from a NSL template are restricted to hexagonally-ordered triangular arrays because the metal layer is deposited onto the interstices between the nanospheres. Metallic nanodisc arrays with the same arrangement as the original nanosphere array have been rarely reported. Here, we demonstrate a facile, low-cost method to fabricate large-area hexagonal arrays of metallic nanodiscs using an NSL template combined with a two-step lift-off process. We employ a bi-layer of two dissimilar metals to create a re-entrant sidewall profile to undercut the sacrificial layer and facilitate the final lift off of the metallic nanodiscs. The quality of the nanodisc pattern and the array periodicity is determined using statistical image analysis and compared to the original nanosphere array in terms of size distribution, surface smoothness, and array pitch. This nanodisc array is used as an etch mask to create a vertically aligned Si nanowire array. This combined approach is a scalable and inexpensive fabrication method for creating relatively large-area, ordered arrays of various nanostructures. PMID- 27559984 TI - Comparison of false-negative/positive results of intraoperative evoked potential monitoring between no and partial neuromuscular blockade in patients receiving propofol/remifentanil-based anesthesia during cerebral aneurysm clipping surgery: A retrospective analysis of 685 patients. AB - Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery. PMID- 27559987 TI - Core vocabulary in written personal narratives of school-age children. AB - This study aimed to describe core words of written personal narratives to inform the implementation of AAC supports for literacy instruction. Investigators analyzed lexical diversity, frequency of specific word use and types of words that made up 70% of the total words used in 211 written narrative samples from children in first grade (n = 94) and fourth grade (n = 117). Across grades, 191 different words made up 70% of the total words used in the 211 written narrative samples. The top 50 words were comprised of content words (64%) and function words (36%). Grade differences were noted in diversity and types of words, including differences in the number of words comprising the core (132 words for children in first grade and 207 for fourth grade) and a higher proportion of abstract nouns for children in fourth grade based on the 200 most frequently occurring words for each grade. PMID- 27559988 TI - Pronounced Dielectric and Hydration/Dehydration Behaviors of Monopolar Poly(N alkylglycine)s in Aqueous Solution. AB - Poly(N-methylglycine) (NMGn) and poly(N-ethylglycine) (NEGn) obtained by polymerization reactions initiated by benzylamine have no carboxy termini, such as those in normal polyamides, but have only amino termini, which exist primarily as cations in aqueous media at a pH value of ca. 9.5, observed in aqueous solutions without any buffer reagents. Therefore, polypeptoids, such as NMGn and NEGn, possessing a degree of polymerization (DP) higher than a certain value behave as cationic monopolar polymeric chain molecules in aqueous solution. It has not been clarified so far whether such a monopolar chain molecule exhibits dielectric relaxation (DR) behavior resulting from its molecular motions in aqueous media as dipolar chain molecules. DR measurements revealed that NMG19 and NEG17, possessing DPs of 19 and 17, respectively, dissolved in pure water clearly demonstrated pronounced DR behavior caused by fluctuating molecular motions of cationic termini at relaxation times of ca. 4 and 9 ns at 10 degrees C (283 K). The hydration numbers of NMG19 and NEG17 per monomeric residue (nm) in aqueous solution were also evaluated via DR data as functions of temperature, and the nm value of ca. 4.5 at 10 degrees C showed a remarkable reduction to ca. 2.0 around 40 degrees C (313 K) and 30 degrees C (303 K), depending on differences in the substituted group: methyl and ethyl groups. This temperature-dependent hydration/dehydration behavior found in NMG19 and NEG17 slightly influenced the sizes and molecular dynamics of the monopolar chain molecules in aqueous solution. PMID- 27559989 TI - Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils. AB - Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully processed collagen using conservative bounds. More realistic bounds may leave no consistent concentrations. Therefore, we propose that unprocessed pC-collagen diffuses from the bundle periphery followed by local C-proteinase activity and subsequent collagen incorporation at each fibril. We suggest that C-proteinase is localized within bundles, at fibril surfaces, during radial fibrillar growth. The much greater critical concentration of pC-collagen, as compared to fully processed collagen, then provides broad consistency between homogeneous fibril radii and the lack of fibril nucleation during fibril growth. PMID- 27559990 TI - Depressive symptoms and autobiographical memory: A pilot electroencephalography (EEG) study. AB - INTRODUCTION: Functional magnetic resonance imaging studies have shown changes in the activity of medial prefrontal, medial temporal, and occipital regions in major depressive disorder patients during recall of autobiographical memories. Electrophysiological underpinning of these changes is not known. It is also not clear whether they are a part of the clinical picture or appear at preclinical stages in individuals predisposed to depression. METHOD: In this study, the effect of depressive symptoms, as measured by the Beck Depression Inventory (BDI II), on oscillatory dynamics accompanying retrieval of emotionally positive and negative autobiographical memories was investigated in a nonclinical sample using electroencephalographic event-related spectral power and connectivity measures. RESULTS: Psychometric results showed that BDI scores correlated positively with the strength of negative emotion, vividness of negative memories, and their importance for participant's life. In high BDI scorers, low-frequency synchronization, which is frequently used as a marker of emotional arousal, prevailed in negative episodes, whereas in low BDI scorers it prevailed in positive episodes. sLORETA localized sources of this synchronization in the medial prefrontal cortex. In negative episodes, depressive symptoms were associated with a diminished event-related connectivity in the alpha band in posterior regions and increased connectivity in beta and gamma bands in frontal regions. CONCLUSIONS: Overall, these results show that even at preclinical stages, depressive symptoms are associated with changes in electrophysiological processes accompanying retrieval of autobiographical memories. PMID- 27559991 TI - Reply to the commentary of Dr. Josue Lily Vidal: Paper: Prevalence of Lebanese stroke survivors: A comparative pilot study. PMID- 27559992 TI - Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 1. Mammalian toxicology. AB - Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons, primarily linear alkanes, with increasing amounts of branched (methyl-groups) alkanes as the chains get longer. In addition, small amounts of cycloalkanes (branched cyclopentanes and cyclohexanes) may be formed as the polymerization reaction prolongs. This synthetic crude can subsequently be refined to a range of products very similar to petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic constituents and also no sulfur-, oxygen-, or nitrogen-containing constituents are present. From a regulatory perspective, GTL products are new substances which require extensive testing to assess their hazardous properties. As a consequence, a wide range of GTL products, covering the entire portfolio of GTL products, have been tested over the past few years in a wide variety of toxicological studies, including reproductive and prenatal development toxicity studies. This review provides an overview of the hazardous properties of the various GTL products. In general, the data collected on GTL products provide strong proof that they exert minimal health effects. In addition, these data provide supporting evidence for what is known on the mechanisms of mammalian toxicology of their petroleum-derived analogs. In the few cases where adverse effects were found for the GTL substances, these were usually less severe than the adverse effects observed with their petroleum-derived analogs. PMID- 27559994 TI - Introduction to the special focus on the UK National Immunisation Conference 2015. PMID- 27559993 TI - Becoming a member of the team. AB - Changes in modern medicine, ranging from duty hour limitations to compression of on-service time, have transformed the dynamics of medical teams. In this piece, the author explores the impact that these changes have had on both medical education and physician and trainee well-being. PMID- 27559995 TI - Surface functionalization of tissue culture polystyrene plates with hydroxyapatite under body fluid conditions and its effect on differentiation behaviors of mesenchymal stem cells. AB - The surfaces of polystyrene (PS) cell culture plates were functionalized with hydroxyapatite (HAp) under body fluid conditions utilizing protein adsorption layers and a pretreatment with an alternate soaking process (ASP) using solutions containing calcium and phosphate ions. Adsorption layers of human serum albumin (HSA) formed on the surface of each well of commercial 24-well PS plates by solution processes. CaCl2 and K2HPO4 solutions were alternately added to the wells, the plates were incubated to form the precursors, and this was followed by the addition of simulated body fluid (SBF) and a further incubation for 24h. These treatments resulted in the surfaces of the PS cell culture plates being completely covered with bone-like HAp. The coating of PS plates with HAp promoted the adhesion of mesenchymal stem cells (MSCs) and maintained cell growth that was as fast as that on tissue culture-treated PS (TCPS) plates. Osteogenic differentiation was greater, whereas adipogenic and chondrogenic differentiation was less in the culture on HAp-coated PS plates than in that on TCPS plates. The present method is useful for preparing HAp-coated PS plates at clean benches without the need for any expensive apparatus. HAp coated on PS plates by this method was a bone-like apatite with high bioactivity; therefore, the present HAp coated PS plates are promising materials for assays of bone-related cells in the bone remodeling process. PMID- 27559996 TI - Effects of Pluronic F127-PEG multi-gel-core on the release profile and pharmacodynamics of Exenatide loaded in PLGA microspheres. AB - Pluronic F127 and PEG as a multi-gel-core were used to prepare Exenatide-loaded microspheres and store the drug within the microspheres. Also, the sol-gel transition and novel functions of the Pluronic F127-PEG gel core were investigated.Microspheres with a multi-gel-core (GCMs) and without a multi-gel core (Ms) were compared in terms of the rate of PLGA degradation, therelease kinetics in vitro and the efficacy in KKAy mice. The drug release of GCMs was at a constant rate, and slower than Ms. In addition, after the KKAy mice were given Exenatide for 55days, the blood glucose concentration and HbA1c concentration in the GCMs group were lower than that in the Ms group. The obtained results demonstrated that a single injection of GCMs allowed the mice to maintain a stable blood glucose concentration for two weeks and their body weight was reduced more effectively than that in the Ms group. In addition, GCMs had a longer interval between dosing (two weeks) and a lower dosage(2.4MUg/kg) than Bydureon((r)) (one week, 33MUg/kg). The bioactivity and release of macromolecular Exenatide was improved by the multi-gel-core structure:(1)The hydrophilic Exenatide tended to partition into the PEG chains of F127 and PEG homopolymer, and so it was protected from the organic solvent and vigorous stirring; (2)The macromolecular Exenatide was released both by diffusing through the hydrophilic F127-PEG chains and hydrophobic PLGA. PMID- 27559997 TI - A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer. AB - HIF-1alpha and LDH-A are important targets for hypoxia-driven drug resistance. Mitochondria targeted fluorescent manganese(II)-complexes can be used as potential fluorescence imaging agents, MRI contrast agents and HIF-1alpha and LDH A involved anticancer complexes. In this study, a fluorescent manganese(II) nanoparticle, labeled as (PEG-Mn-BDA), was synthesized and used as both fluorescent and MRI imaging agents in cancer cells. In vitro bioassay results indicate that PEG-Mn-BDA was able to inhibit LDH-A activity and depolarize mitochondrial membrane potential with the generation of intracellular ROS, which contributed to the induction of apoptosis. Moreover, the pro-apoptotic protein, caspase 3 was highly expressed. In vivo, PEG-Mn-BDA could also exert inhibition on a mouse hepatocellular carcinoma xenograft. These results suggest that mitochondria targeted PEG-Mn-BDA was able to simultaneously induce selective inhibition on cancer cells and a mouse carcinoma xenograft, label cancer cells with fluorescence and enhance MRI contrast. Therefore, PEG-Mn-BDA is a good candidate for cancer treatment and imaging. PMID- 27559999 TI - Preparation of a thermoresponsive polymer grafted polystyrene monolithic capillary for the separation of bioactive compounds. AB - To develop aqueous microseparation columns for bioactive compounds, a thermoresponsive polymer grafted polymer monolith was prepared inside silica capillaries having an I.D. of 100MUm by polymerization of styrene (St) with m/p divinylbenzene (DVB) in the presence of polydimethylsiloxane as porogen, followed by surface-initiated atom transfer radical polymerization (SI-ATRP) of N isopropylacrylamide (NIPAAm). SEM analysis indicated that the resulting poly(N isopropylacrylamide) (PNIPAAm) grafted polystyrene monolith had a consecutive three-dimensionally interconnected structure and through-pores, similar to the base polystyrene (PSt) monolith. The elution behavior of steroids with different hydrophobicity was evaluated using micro-high-performance liquid chromatography in sole aqueous mobile phase. Temperature dependent interaction changes were observed between steroids and the PNIPAAm modified surfaces. Furthermore, the interaction between bioactive compounds and the PNIPAAm grafted PSt surfaces was controlled and eventually separate these molecules with different hydrophobicities by simple temperature modulation in aqueous environment. The PNIPAAm grafted PSt monolithic capillary showed improved separation properties of bioactive compounds, compared with a PNIPAAm grafted hollow capillary in aqueous environment. PMID- 27559998 TI - Osteogenic activity and antibacterial effect of zinc oxide/carboxylated graphene oxide nanocomposites: Preparation and in vitro evaluation. AB - The aim of this study was to prepare nanocomposites of carboxylated graphene oxide (GO-COOH) sheets decorated with zinc oxide (ZnO) nanoparticles (NPs) and investigate their advantages in the field of bone tissue engineering. First, ZnO/GO-COOH nanocomposites were synthesized by facile reactions, including the carboxylation of graphene oxide (GO) and the nucleation of ZnO on GO-COOH sheets. The synthesized ZnO/GO-COOH nanocomposites were then characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectra, and transmission electron microscopy (TEM). The biocompatibility, osteogenic activity and antibacterial effect of ZnO/GO-COOH nanocomposites were further investigated. In the nanocomposites, ZnO nanoparticles with a size of approximately 12nm were uniformly decorated on GO-COOH sheets. Compared with GO-COOH and the control group, ZnO/GO-COOH nanocomposites significantly enhanced ALP activity, osteocalcin production and extracellular matrix mineralization as well as up regulated osteogenic-related genes (ALP, OCN, and Runx2) in MG63 osteoblast-like cells. Moreover, ZnO/GO-COOH nanocomposites had an antibacterial effect against Streptococcus mutans. These results indicated that ZnO/GO-COOH nanocomposites exhibited both osteogenic activity and antibacterial effect and had great potential for designing new biomaterials in the field of bone tissue engineering. PMID- 27560000 TI - Effect of the cross-linking agent on performances of NaCS-CS/WSC microcapsules. AB - Based on the properties of oppositely charged natural polysaccharides, the polyelectrolyte complexes (PECs) prepared with chitosan-related polycationic polyelectrolytes and cellulose-related polyanionic polyelectrolytes have been widely concerned for their potential applications as micro-drug-carriers for colon. However, the poor mechanical property of the PECs becomes the obstacle encountered in practical applications. This study investigated the effect of the cross-linking agent (sodium polyphosphate, PPS) on the performances of sodium cellulose sulfate -chitosan/water soluble chitosan (NaCS-CS/WSC) microcapsules. The results revealed that PPS could penetrate through the PEC film and form tighter interior structures compared with the microcapsules without the addition of cross-linking agent. The NaCS-CS microcapsules and NaCS-WSC microcapsules with or without PPS had distinct microstructures, which could be ascribed to the different physicochemical properties of CS and WSC. During the formation process, CS can be dissolved in water under acidic conditions, while WSC can be directly dissolved and protonated in acid-free aqueous providing NH3(+) groups quickly, which resulted in the microstructure's difference. Further analysis showed the NaCS-CS-PPS microcapsules and NaCS-WSC-PPS microcapsules had lower swelling ratios due to their tighter interior microstructures that formed. The cross linking agent had important effect on the total mass of PECs that produced; moreover, the decline of zeta potential of NaCS-CS-PPS microcapsules was lower than that of NaCS-CS microcapsules, similar trend was found in the NaCS-WSC-PPS microcapsules compared with NaCS-WSC microcapsules, indicating the PPS participated in the interactions and played a role in the microcapsules' formation process. PMID- 27560001 TI - A sulfurization-based oligomeric sodium salt as a high-performance organic anode for sodium ion batteries. AB - An attractive organic electrode material, oligomeric sodium salt, is prepared by polymerization of chloranilic acid through thioether bonds. It exhibits a superior sodium-storage performance with high specific capacity, good rate capability and excellent cyclability, benefitting from the conjugative effect of the benzene ring group and the intrinsic electrolyte-insoluble ability. PMID- 27560005 TI - The effect of continuous positive airway pressure on heart rate variability during the night in patients with chronic heart failure and central sleep apnoea. AB - Continuous positive airway pressure (CPAP) improves autonomic activity in patients with chronic heart failure (CHF) and central sleep apnoea (CSA), but its effect on heart rate variability (HRV) during therapy has not been reported. We hypothesized that CPAP may decrease HRV, despite its beneficial effects on sympathetic overactivation, due to the expected stabilization of breathing. Sixty seven CHF patients underwent polysomnography (PSG). Ten of them presented with CSA (age 66.1+/-8.5 years, apnoea-hypopnea index [AHI]=57.6+/-23.3, central AHI [cAHI]=41.6+/-24.6 [mean+/-SD]) and were subjected to a second PSG with manual CPAP titration. Beat-to-beat heart intervals for a 6-hour period of sleep were extracted from each recording and HRV was analysed. CPAP significantly reduced AHI (AHI=23.1+/-18.3 P=.004). Standard deviation of normal-normal interbeat interval (SDNN) (61.5+/-29.0 vs 49.5+/-19.3 ms, P=.021), root mean square of successive differences (RMSSD) (21.8+/-9.2 vs 16.4+/-7.1 ms, P=.042), total power (lnTP=7.8+/-1.1 vs 7.4+/-0.8 ms2 , P=.037), low frequency power (lnLF=5.5+/-1.5 vs 5.0+/-1.4 ms2 , P=.003) and high frequency power (lnHF=4.6+/-1.0 vs 4.0+/-1.0 ms2 , P=.024) were decreased. There was a strong correlation between the decrease in AHI and the decrease in lnHF (Spearman's rho=.782). CPAP leads to a decrease in spectral and time domain parameters of HRV during therapy in CHF patients with CSA. These changes are best explained by the effect which CPAP-influenced breathing pattern and lowered AHI exert on HRV. PMID- 27560004 TI - Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells. AB - Among all tissues of the metazoa, the transcritpome of testis displays the highest diversity and specificity. However, its composition and dynamics during spermatogenesis have not been fully understood. Here, we have identified 20,639 message RNAs (mRNAs), 7,168 long non-coding RNAs (lncRNAs) and 15,101 circular RNAs (circRNAs) in mouse spermatogenic cells, and found many of them were specifically expressed in testes. lncRNAs are significantly more testis-specific than mRNAs. At all stages, mRNAs are generally more abundant than lncRNAs, and linear transcripts are more abundant than circRNAs. We showed that the productions of circRNAs and piRNAs were highly regulated instead of random processes. Based on the results of a small-scale functional screening experiment using cultured mouse spermatogonial stem cells, many evolutionarily conserved lncRNAs are likely to play roles in spermatogenesis. Typical classes of transcription factor binding sites are enriched in the promoters of testis specific m/lncRNA genes. Target genes of CREM and RFX2, 2 key TFs for spermatogenesis, were further validated by using ChIP-chip assays and RNA-seq on RFX2-knockout spermatogenic cells. Our results contribute to the current understanding of the transcriptomic complexity of spermatogenic cells and provide a valuable resource from which many candidate genes may be selected for further functional studies. PMID- 27560007 TI - Five common clinical presentations in the elderly: An anatomical review. AB - Elderly patients face distinct health challenges and have an increased demand for specific medical procedures. As the aging population continues to increase, age associated conditions such as congestive heart failure, hip fractures, spine degeneration, dementia, and airway compromise will increase in prevalence and procedures to correct these conditions will be increasingly performed. A clear understanding of the clinical anatomy of these diseases and procedures is imperative for anatomists and clinicians alike in order to best treat patients and continue to advance aging research and better teach future medical practitioners about the specific anatomy often involved in this group. The aging process mirrors in a variety of ways the common pathologies of the elderly, but it is key to draw the distinction between normal aging and pathology, particularly for congestive heart failure and dementia, in the clinical setting. This article aims to review the common presentations or procedures of the elderly and how the normal aging process is associated with the anatomy of these conditions or complications. Clin. Anat. 30:168-174, 2017. (c) 2017 Wiley Periodicals, Inc. PMID- 27560008 TI - Deoxyfluoro-d-trehalose (FDTre) analogues as potential PET probes for imaging mycobacterial infection. AB - Mycobacterium tuberculosis, the etiological agent of human tuberculosis, requires the non-mammalian disaccharide trehalose for growth and virulence. Recently, detectable trehalose analogues have gained attention as probes for studying trehalose metabolism and as potential diagnostic imaging agents for mycobacterial infections. Of particular interest are deoxy-[(18)F]fluoro-d-trehalose ((18)F FDTre) analogues, which have been suggested as possible positron emission tomography (PET) probes for in vivo imaging of M. tuberculosis infection. Here, we report progress toward this objective, including the synthesis and conformational analysis of four non-radioactive deoxy-[(19)F]fluoro-d-trehalose ((19)F-FDTre) analogues, as well as evaluation of their uptake by M. smegmatis. The rapid synthesis and purification of several (19)F-FDTre analogues was accomplished in high yield using a one-step chemoenzymatic method. Conformational analysis of the (19)F-FDTre analogues using NMR and molecular modeling methods showed that fluorine substitution had a negligible effect on the conformation of the native disaccharide, suggesting that fluorinated analogues may be successfully recognized and processed by trehalose metabolic machinery in mycobacteria. To test this hypothesis and to evaluate a possible route for delivery of FDTre probes specifically to mycobacteria, we showed that (19)F-FDTre analogues are actively imported into M. smegmatis via the trehalose-specific transporter SugABC-LpqY. Finally, to demonstrate the applicability of these results to the efficient preparation and use of short-lived (18)F-FDTre PET radiotracers, we carried out (19)F-FDTre synthesis, purification, and administration to M. smegmatis in 1 hour. PMID- 27560009 TI - Spectroscopic Characterization of Gliosarcomas-Do They Differ From Glioblastomas and Metastases? AB - OBJECTIVE: To evaluate the spectroscopic pattern of gliosarcomas for differentiation from glioblastomas or metastases. METHODS: H-nuclear magnetic resonance (NMR) spectroscopic intermediate echo time data of 5 patients with histologically proven gliosarcomas were compared with data of 17 metastases and 54 glioblastomas. Specialized H-NMR spectroscopy analysis software was used offline. Lipid and macromolecular resonances between 0.9 ppm and 1.4 ppm were compared besides the main metabolites using the Mann-Whitney U test. RESULTS: Gliosarcomas showed higher lipid and macromolecule resonances and a higher lipid choline ratio compared with glioblastomas (P < 0.024 and P < 0.036). Glioblastomas showed higher creatine concentrations compared with metastases (P < 0.007) but not compared with gliosarcomas. We found no significant differences between metastases and gliosarcomas. CONCLUSIONS: Gliosarcomas may mimic metastases on H NMR spectroscopy showing high signal intensities from lipid and macromolecule resonances. This tumor type should be suspected if conventional imaging suggests an intra-axial brain neoplasm in combination with high lipids in solid tumor parts. PMID- 27560010 TI - Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid for Quantitative Assessment of Vascular Effects on Hepatocellular-Carcinoma Lesions Treated by Transarterial Chemoembolization or Radiofrequency Ablation. AB - PURPOSE: The aim of this study was to investigate the role of dynamic contrast enhanced magnetic resonance imaging (MRI) in evaluation of blood flow changes related to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) procedures in patients with hepatocellular carcinoma (HCC) lesions. METHODS: Fifty-four patients, with biopsy-proven HCC, who underwent TACE or RFA, were evaluated, 1 month after treatment, with upper abdominal MRI examination. Multiplanar T2-weighted, T1-weighted, and dynamic contrast-enhanced sequences were acquired. Dedicated perfusion software (T1 Perfusion Package, Viewforum; Philips Medical Systems, The Netherlands) was used to generate color permeability maps. After placing regions of interest in normal hepatic parenchyma, in successfully treated lesions, and in area of recurrence, the following perfusion parameters were calculated and statistically analyzed: relative arterial, venous, and late enhancement; maximum enhancement; maximum relative enhancement, and time to peak. RESULTS: Twenty-one of 54 patients had residual disease, and perfusion parameters values measured within tumor tissue were: relative arterial enhancement median, 42%; relative venous enhancement median, 69%; relative late enhancement median, 57.7%; maximum enhancement median, 749.6%; maximum relative enhancement median, 69%; time to peak median, 81.1 seconds. As for all the evaluated parameters, a significant difference (P < 0.05) was found between residual viable tumor tissue and effective treated lesions. CONCLUSIONS: Dynamic contrast-enhanced MRI represents a complementary noninvasive tool that may offer quantitative and qualitative information about HCC lesions treated with TACE and RFA. PMID- 27560011 TI - A Quantitative Approach to Distinguish Pneumonia From Atelectasis Using Computed Tomography Attenuation. AB - OBJECTIVE: It is known that atelectasis demonstrates greater contrast enhancement than pneumonia on computed tomography (CT). However, the effectiveness of using a Hounsfield unit (HU) threshold to distinguish pneumonia from atelectasis has never been shown. The objective of the study is to demonstrate that an HU threshold can be quantitatively used to effectively distinguish pneumonia from atelectasis. METHODS: Retrospectively identified CT pulmonary angiogram examinations that did not show pulmonary embolism but contained nonaerated lungs were classified as atelectasis or pneumonia based on established clinical criteria. The HU attenuation was measured in these nonaerated lungs. Receiver operating characteristic (ROC) analysis was performed to determine the area under the ROC curve, sensitivity, and specificity of using the attenuation to distinguish pneumonia from atelectasis. RESULTS: Sixty-eight nonaerated lungs were measured in 55 patients. The mean (SD) enhancement was 62 (18) HU in pneumonia and 119 (24) HU in atelectasis (P < 0.001). A threshold of 92 HU diagnosed pneumonia with 97% sensitivity (confidence interval [CI], 80%-99%) and 85% specificity (CI, 70-93). Accuracy, measured as area under the ROC curve, was 0.97 (CI, 0.89-0.99). CONCLUSIONS: We have established that a threshold HU value can be used to confidently distinguish pneumonia from atelectasis with our standard CT pulmonary angiogram imaging protocol and patient population. This suggests that a similar threshold HU value may be determined for other scanning protocols, and application of this threshold may facilitate a more confident diagnosis of pneumonia and thus speed treatment. PMID- 27560012 TI - Adaptive Statistical Iterative Reconstruction-V: Impact on Image Quality in Ultralow-Dose Coronary Computed Tomography Angiography. AB - OBJECTIVE: The clinical utility of a latest generation iterative reconstruction algorithm (adaptive statistical iterative reconstruction [ASiR-V]) has yet to be elucidated for coronary computed tomography angiography (CCTA). This study evaluates the impact of ASiR-V on signal, noise and image quality in CCTA. METHODS: Sixty-five patients underwent clinically indicated CCTA on a 256-slice CT scanner using an ultralow-dose protocol. Data sets from each patient were reconstructed at 6 different levels of ASiR-V. Signal intensity was measured by placing a region of interest in the aortic root, LMA, and RCA. Similarly, noise was measured in the aortic root. Image quality was visually assessed by 2 readers. RESULTS: Median radiation dose was 0.49 mSv. Image noise decreased with increasing levels of ASiR-V resulting in a significant increase in signal-to noise ratio in the RCA and LMA (P < 0.001). Correspondingly, image quality significantly increased with higher levels of ASiR-V (P < 0.001). CONCLUSIONS: ASiR-V yields substantial noise reduction and improved image quality enabling introduction of ultralow-dose CCTA. PMID- 27560014 TI - Computed Tomography Appearance of Surgically Resected Adrenal Hematomas. AB - OBJECTIVE: Adrenal hemorrhages arise as a result of a number of conditions and may exhibit a variety of appearances on computed tomography (CT). On occasion, patients will undergo adrenalectomy for treatment of a presumptive adrenal neoplasm that on surgical pathology is identified as an adrenal hemorrhage. We evaluated the CT appearance of surgically resected adrenal masses from our institution over a period of 15 years that ultimately proved to be adrenal hematomas. METHODS: A surgical pathology archive was queried for all cases of adrenal hemorrhage. Only cases with a corresponding diagnostic CT were included. Cases were excluded if an underlying adrenal mass was present. For the remaining cases, the CT appearances were evaluated by 2 radiologists quantitatively and qualitatively. RESULTS: Our search yielded 18 cases of adrenal hemorrhage, of which 5 cases had corresponding CT and no underlying secondary process within the adrenal. All of the adrenal hematomas in this series demonstrated an ovoid morphology and were well defined, with an average maximum diameter of 8.9 cm and highly variable attenuation on noncontrast CT (average attenuation range, 13.1 44.0 Hounsfield units [HU]). Four of the 5 lesions had degrees of peripheral enhancement that was either thin and somewhat uniform or heterogeneous and irregular. None of the lesions demonstrated invasion of the periadrenal fat or adjacent organs. CONCLUSIONS: Adrenal hematomas with a mass-like configuration offer a potential diagnostic dilemma for radiologists and surgeons. Although it is rare that an adrenal hemorrhage is surgically resected, awareness of the potential appearances of these lesions is important to spare patients from unnecessarily aggressive surgery. PMID- 27560013 TI - Optimized Protocol for Fast CT Angiography of Lower Limbs Using 160-Row Detector. AB - OBJECTIVE: We proposed and tested a novel acquisition protocol for optimizing a fast computed tomography angiography using a 160-row detector scanner using a longer contrast injection time coupled with multiphasic rate of injection. METHODS: A prospective randomized study was performed to compare image quality, contrast enhancement, and radiation dose in 2 groups (a fast acquisition and a widely accepted slow acquisition). RESULTS: There was no difference between groups regarding image quality, noise, and diagnostic performance, but we evidenced a trend to higher radiation dose for the fast acquisition protocol. CONCLUSIONS: An optimized protocol for performing a fast acquisition computed tomography angiography of lower limbs is feasible, has sufficient diagnostic quality, and can be used in selected patients who would benefit from a short-time scan. PMID- 27560015 TI - Computed Tomography Features of Appendiceal Metastasis in Patients With Underlying Malignancy: Comparison With Pathological Findings. AB - OBJECTIVE: To evaluate the computed tomography (CT) findings compared with pathologic features and to determine whether CT findings are useful for diagnosis of appendiceal metastasis in patients with underlying malignancy. MATERIALS AND METHODS: Preoperative CT examinations of 59 patients who had underlying malignancy and underwent appendectomy were evaluated. Appendiceal metastasis (n = 21) and nonmetastasis (n = 38) were pathologically confirmed. Computed tomography features (appendiceal morphology and diameter, presence of ascites, rectal shelf, omental cake, lymphadenopathy or organ metastasis) were retrospectively reviewed, and compared with histopathological findings. Fisher exact test and Wilcoxon rank sum test were performed for statistical analysis. RESULTS: Mean diameter of appendiceal metastasis was significantly larger (9.1 mm) than that of nonmetastasis (5.2 mm), (P < 0.0001). The CT morphology of appendiceal metastasis showed broad spectrum, and 3 cases of nodular thickening was only detected in appendiceal metastasis. There was a significant difference between groups (P = 0.0102). Appendiceal metastasis was more frequently associated with peritoneal seeding (ascitis, rectal shelf, omental cake) than nonmetastasis (P < 0.0001). Histopathological invasion of appendiceal metastasis was more frequently seen in serosa-mesoappendix (n = 20, 100%) or muscularis propria (n = 17, 85%), than in submucosa (n = 10, 50%) or mucosa layer (n = 7, 35%). Acute appendicitis was more commonly detected in metastasis (n = 4) than in nonmetastasis (n = 1) (P = 0.0495). CONCLUSIONS: Evaluation of CT features of appendix and peritoneum may be useful for prediction of appendiceal metastasis in patients with underlying malignancy. PMID- 27560016 TI - Computed Tomographic Angiography of the Abdomen and Pelvis in Azotemic Patients Utilizing 80-kV(p) Technique and Reduced Dose Iodinated Contrast: Comparison With Routine 120-kV(p) Technique. AB - OBJECTIVE: To evaluate image quality (IQ) of a reduced contrast volume, low kilovolt (peak) [kV(p)] abdominopelvic computed tomographic angiography (AP-CTA) protocol compared to a standard 120-kV(p) AP-CTA protocol. METHODS: A retrospective image analysis was performed on 103 patients with end-stage renal disease who underwent AP-CTA. Forty-nine patients were scanned at 80 kV(p) with a mean of 48 mL of contrast, and 54 patients were scanned at 120 kV(p) with a mean of 98 mL of contrast. Objective comparison of arterial attenuation, noise, and contrast-to-noise ratio was obtained, in addition to radiation dose. Subjective assessment of IQ, enhancement intensity, and image noise (IN) was scored on a 3 point scale. RESULTS: The 6-level aggregate contrast-to-noise ratio for the 80 kV(p) group was 11.8 +/- 7.0, compared to 12.4 +/- 4.6 in the 120-kV(p) group (P = 0.210). Radiation exposure was significantly lower in the 80-kV(p) group versus the 120-kV(p) group, as measured by average CT dose index (mGy) of 9.0 +/- 3.1 and 15.8 +/- 5.8 (P < 0.0001), respectively; and average dose length product (mGy * cm) of 490.0 +/- 214.1 and 863.1 +/- 344.4 (P < 0.0001), respectively. The 120 kV(p) technique scored better for subjective IQ (P = 0.042) and IN (P = 0.004) but not for enhancement intensity (P = 0.205). CONCLUSIONS: A 50% reduced iodinated contrast dose coupled with 80-kV(p) technique with iterative reconstruction allows for satisfactory AP-CTA studies at a 43% mean radiation dose reduction compared to a standard protocol. Negative but potentially reversible sequelae of this drop in radiation dose include increased IN and reduced subjective IQ. PMID- 27560017 TI - Aortic Valve and Thoracic Aortic Calcification Measurements: How Low Can We Go in Radiation Dose? AB - OBJECTIVE: This study aimed to determine the lowest radiation dose and iterative reconstruction level(s) at which computed tomography (CT)-based quantification of aortic valve calcification (AVC) and thoracic aortic calcification (TAC) is still feasible. METHODS: Twenty-eight patients underwent a cardiac CT and 20 patients a chest CT at 4 different dose levels (routine dose and approximately 40%, 60%, and 80% reduced dose). Data were reconstructed with filtered back projection, 3 iDose levels, and 3 iterative model-based reconstruction levels. Two observers scored subjective image quality. The AVC and TAC were quantified using mass and compared to the reference scan (routine dose reconstructed with filtered back projection). RESULTS: In cardiac CT at 0.35 mSv (60% reduced), all scans reconstructed with iDose (all levels) were diagnostic, calcification detection errors occurred in only 1 patient, and there were no significant differences in mass scores compared to the reference scan. Similar results were found for chest CT at 0.48 mSv (75% reduced) with iDose levels 4 and 6 and iterative model reconstruction levels 1 and 2. CONCLUSIONS: Iterative reconstruction enables AVC and TAC quantification on CT at submillisievert dose. PMID- 27560018 TI - Adhesive Capsulitis of the Shoulder Joint: Value of Glenohumeral Distance on Magnetic Resonance Arthrography. AB - OBJECTIVE: To evaluate the usefulness of glenohumeral distance (GHD) on axial images of magnetic resonance (MR) arthrography for diagnosis of adhesive capsulitis and to compare this finding with previously reported classic MR arthrographic findings of adhesive capsulitis. MATERIALS AND METHODS: Our study was approved by the institutional ethical review board of our institute. We evaluated 41 patients (M-F, 35:6; mean age, 46 years; adhesive capsulitis, 21; no adhesive capsulitis, 20) who underwent MR arthrography. Two radiologists measured GHD, width of the axillary recess, and capsular thickness in consensus. The GHD was measured from the subchondral bone of the glenoid fossa to the subchondral bone of the humeral head at the level of the midline of the humeral head. Glenohumeral distance (anterior, middle, posterior, and mean), width of the axillary recess, and capsular thickness (anterior, posterior, and mean) were compared in the adhesive capsulitis and no adhesive capsulitis groups using the Mann-Whitney U test. RESULTS: The mean GHD of the no adhesive capsulitis group was longer than that of the adhesive capsulitis group. The length differences were statistically significant (P < 0.05). The mean width of the axillary recess of the no adhesive capsulitis group was significantly wider than that of the adhesive capsulitis group (P < 0.001). The mean capsular thickness of the no adhesive capsulitis group was significantly thinner than that in the adhesive capsulitis group (P = 0.001). CONCLUSIONS: A decreased GHD on MR arthrography can be another useful feature to diagnose adhesive capsulitis in addition to previously presented radiologic features such as capsular thickening and reduced axillary recess capacity. PMID- 27560019 TI - A Large Cohort Study of 18F Fluoro-Deoxy-Glucose Uptake in Normal Spinal Cord: Quantitative Assessment of the Contamination From Adjacent Vertebral Marrow Uptake and Validity of Normalizing the Cord Uptake Against the Lumbar Thecal Sac. AB - PURPOSE: This study aimed (1) to assess the influence of age, sex, blood glucose, and body mass index on the F fluoro-deoxy-glucose (F-FDG) uptake in normal spinal cord; (2) to quantitatively evaluate contamination of the spinal cord SUVmax by the adjacent vertebral marrow activity; and (3) to investigate the validity of normalizing spinal cord SUVmax against lumbar thecal sac SUVmax. METHODS: Two hundred positron emission tomography-computed tomography examinations of subjects with normal spinal cord were retrospectively reviewed. SUVmax of spinal cord and vertebral body was obtained at C2, C5, T6, T12, and L3 levels. Pearson correlation coefficients (r) were obtained at each level between spinal cord SUVmax and vertebral marrow SUVmax, age, body mass index, and blood glucose. Cord to background ratio (CTB) was calculated as the ratio between SUVmax of spinal cord and SUVmax of L3 thecal sac. The coefficient of variation (CV) of spinal cord SUVmax was compared with the CV of CTB. RESULTS: Spinal cord SUVmax was highest at C2 (mean, 1.76) and lowest at T6 (mean, 1.37) with SD of 0.32 to 0.36 SUV. Sex (P > 0.45), age (r: -0.25 to -0.06), body mass index (r: 0.19 to 0.27), and blood glucose (r: -0.17 to 0.22) had no impact on the spinal cord SUVmax. A moderate to strong positive correlation (r: 0.66-0.80) was found between spinal cord SUVmax and the corresponding vertebral marrow SUVmax. The CV of CTB was greater (0.28-0.32) than the CV of spinal cord SUVmax (0.19-0.25) across all levels. CONCLUSIONS: Of the variables studied, only contamination from adjacent vertebral marrow activity significantly affected the SUVmax of spinal cord. This contamination should be corrected for when reporting spinal cord FDG uptake. Lumbar thecal sac is not a valid reference for normalizing spinal cord FDG uptake. PMID- 27560020 TI - Can Discrepancies Between Coronary Computed Tomography Angiography and Cardiac Catheterization in High-Risk Patients be Overcome With Consensus Reading? AB - OBJECTIVE: To assess the incidence and cause of discrepancies between coronary computed tomography angiography (CTA) and catheterization in a high-risk, diverse, predominantly overweight inner-city population. METHODS: Ninety-two patients who underwent coronary CTA and catheterization on March 2007 to December 2012 were retrospectively identified. Clinical coronary CTA interpretation and reinterpretation by a review panel was compared with catheterization results. RESULTS: Severe stenosis was present on catheterization in 65% (60/92). Clinical coronary CTA was concordant with catheterization for severe stenosis in 78% (72/92), whereas panel interpretation was concordant in 77% (70/91). Sensitivity and specificity of clinical and panel coronary CTA interpretations were 92% (55/60) and 53% (17/32) versus 82% (48/59) and 68% (22/32), respectively. CONCLUSIONS: Both coronary CTA interpretations were concordant with catheterization for severe stenosis in three quarters of patients. However, the diagnostic profile of the 2 interpretations differed, with higher sensitivity for the clinical report. This supports the clinical practice, which favored overestimation of difficult to quantify stenoses. PMID- 27560021 TI - Use of a Noise Optimized Monoenergetic Algorithm for Patient-Size Independent Selection of an Optimal Energy Level During Dual-Energy CT of the Pancreas. AB - PURPOSE: To investigate the impact of a second-generation noise-optimized monoenergetic algorithm on selection of the optimal energy level, image quality, and effect of patient body habitus for dual-energy multidetector computed tomography of the pancreas. MATERIALS AND METHODS: Fifty-nine patients (38 men, 21 women) underwent dual-energy multidetector computed tomography (80/Sn140 kV) in the pancreatic parenchymal phase. Image data sets, at energy levels ranging from 40 to 80 keV (in 5-keV increments), were reconstructed using first generation and second-generation noise-optimized monoenergetic algorithm. Noise, pancreatic contrast-to-noise ratio (CNRpancreas), and CNR with a noise constraint (CNRNC) were calculated and compared among the different reconstructed data sets. Qualitative assessment of image quality was performed by 3 readers. RESULTS: For all energy levels below 70 keV, noise was significantly lower (P <= 0.05) and CNRpancreas significantly higher (P < 0.001), with the second-generation monoenergetic algorithm. Furthermore, the second-generation algorithm was less susceptible to variability related to patient body habitus in the selection of the optimal energy level. The maximal CNRpancreas occurred at 40 keV in 98% (58 of 59) of patients with the second-generation monoenergetic algorithm. However, the CNRNC and readers' image quality scores showed that, even with a second generation monoenergetic algorithm, higher reconstructed energy levels (60-65 keV) represented the optimal energy level. CONCLUSIONS: Second-generation noise optimized monoenergetic algorithm can improve the image quality of lower-energy monoenergetic images of the pancreas, while decreasing the variability related to patient body habitus in selection of the optimal energy level. PMID- 27560022 TI - Systematic Review on the Additional Value of 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography in Staging Follicular Lymphoma. AB - PURPOSE: This study aimed to systematically review the additional value of F fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to computed tomography (CT) for staging newly diagnosed follicular lymphoma in terms of Ann Arbor staging and Follicular Lymphoma International Prognostic Index (FLIPI) risk stratification. MATERIALS AND METHODS: The PubMed/MEDLINE database was searched for relevant original studies. Included studies were methodologically assessed. Data on the frequency of FDG-PET-induced changes in Ann Arbor stage and FLIPI score relative to CT were (meta-)analyzed when possible. RESULTS: Seven studies with a total of 349 patients were included. Overall, studies were of very poor methodological quality, with lack of histological verification of additionally detected lesions at FDG-PET in almost all cases and only 1 study that exclusively included patients with CT-based limited nonbulky stage I to II disease. The proportion of patients who were upstaged by FDG-PET compared with CT ranged from 0.0% to 45.2%, with a pooled summary proportion of 18.7% (95% confidence interval, 10.8%-30.4%). The single study that only included patients with CT based limited nonbulky stage I to II disease reported FDG-PET-induced upstaging in 40.5% (95% confidence interval, 27.0%-55.5%) of cases. No study reported data on the influence of FDG-PET on FLIPI risk stratification. CONCLUSIONS: Although upstaging by FDG-PET compared with CT occurs in a considerable proportion of patients, the available studies on this topic have numerous methodological errors. Data on FDG-PET-induced FLIPI risk stratification changes relative to CT are lacking. Future well-designed studies are needed before FDG-PET can be recommended for routine pretreatment staging of follicular lymphoma. PMID- 27560023 TI - A Comparison of the Image Quality and Radiation Dose Using 100-kVp Combination of Different Noise Index and 120-kVp in Computed Tomography Pulmonary Angiography. AB - OBJECTIVE: The objective of our study was to compare the image quality and radiation dose of computed tomography pulmonary angiography (CTPA) in patients with different body mass indexes using 100-kVp combination of different noise indexes (NIs) and 120-kVp scan protocol with the adaptive statistical iterative reconstruction 2.0 algorithm (ASiR 2.0). METHODS: A total of 120 patients who had undergone a CTPA were divided into 4 groups (A, B, C, and D), with 30 patients in each group. Group A underwent 120-kVp CT scan protocol in combination with NI = 25, while groups B, C, and D underwent 100-kVp CT scan protocol in combination with NI = 30, 35, and 40, respectively. All images were restructured using ASiR 2.0. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of all images were calculated when the CTPA was completed. Each subjective image evaluation used a 5-point scoring method and was conducted by 2 independent radiologists. The CT dose index of volume and dose-length product were recorded, and the mean value was calculated. The dose-length product was converted to the effective dose. RESULTS: There were no significant differences in SNR, CNR, and subjective image quality among the groups A, B, C, and D. The effective dose of group D decreased by 48.33% and 27.27% relative to groups A and B, respectively (P < 0.01). CONCLUSIONS: The 100-kVp CT scan protocol in combination with NI = 40 can more effectively reduce the radiation dose than can the 120-kVp CT scan protocol in combination with NI = 25 for a CTPA while still maintaining diagnostic image quality. PMID- 27560024 TI - Myxoinflammatory Fibroblastic Sarcoma: Clinical, Imaging, Management and Outcome in 29 Patients. AB - OBJECTIVE: This retrospective study was undertaken to highlight clinical and magnetic resonance imaging features of myxoinflammatory fibroblastic sarcoma. METHODS: The clinical records of 29 patients (14 men and 15 women) were analyzed. RESULTS: The soft tissue tumors involved hand, wrist, foot and ankle in 21 patients, more proximal extremities in 7 patients, and neck in 1 patient. The tumors were subcutaneous in 11 patients, and intramuscular in 15 patients. On magnetic resonance imaging, these tumors had nonspecific features suggestive of benign and malignant lesions. An unusual tumor in hand indicated infection, whereas an intraarticular knee tumor mimicked pigmented villonodular synovitis. All tumors were surgically resected. CONCLUSIONS: Myxoinflammatory fibroblastic sarcoma, a rare low-grade subcutaneous soft tissue tumor of distal extremities with high local recurrence after resection can mimic several benign and malignant lesions on histopathology and imaging. Rarely, it can arise in muscles and tendons, occur in nonacral sites, be aggressive, and even metastasize. In most cases, surgical resection with wide margins can be curative with low local recurrence. PMID- 27560025 TI - Characterization of Thyroid Nodules by 4-Dimensional Computed Tomography: Initial Experience. AB - OBJECTIVE: We aimed to evaluate the use of 4-dimensional computed tomography (4DCT) for characterization of thyroid nodules. METHODS: Our study drew from 100 consecutive patients with primary hyperparathyroidism who underwent 4D parathyroid CT imaging for adenoma localization. Included subjects had tissue sampling of a thyroid nodule within 3 months of 4DCT. RESULTS: Twenty subjects (18 women and 2 men) had thyroid nodules that were pathologically confirmed. Precontrast nodule attenuation was significantly lower in malignant nodules when compared with benign nodules (36 vs 61 HU, P = 0.05). Arterial phase and delayed phase nodule attenuations were not significantly different in malignant and benign nodules (128 vs 144 HU, P = 0.7; 74 vs 98 HU, P = 0.3). CONCLUSIONS: Our initial experience with a small group of patients was unable to support the use of 4DCT for characterizing thyroid nodules; however, precontrast nodule attenuation was significantly lower in malignant nodules when compared with benign nodules. PMID- 27560026 TI - High-Resolution Diffusion-Weighted Imaging Improves the Diagnostic Accuracy of Dynamic Contrast-Enhanced Sinonasal Magnetic Resonance Imaging. AB - OBJECT: The aim of the study was to evaluate the incremental value of high resolution diffusion-weighted imaging and apparent diffusion coefficient (ADC) mapping compared with that of dynamic contrast-enhanced (DCE) sinonasal magnetic resonance imaging (MRI) in the characterization of benign versus malignant sinonasal tumors at 3.0T. MATERIALS AND METHODS: Ninety-eight patients (61 females, 37 males; mean age, 48 years) with sinonasal lesions who underwent high resolution DW-MRI and DCE-MRI were included in this study. The lesions were divided into malignant and benign groups on the basis of pathological examination. In total, 58 malignant tumors and 40 benign tumors were evaluated. Apparent diffusion coefficients were acquired with 0 and 1000 s/mm b values. Semiquantitative parameters (time-signal intensity curve [TIC] type, time of peak enhancement within the first 2 minutes [Tpeak], peak percentage enhancement within the first 2 minutes [PEpeak], the last time point percentage enhancement [PElast], and the washout percentage-enhancement difference [PEwashout]) were derived from DCE-MRI. The DCE-MRI parameters and ADCs were included in multivariate models to predict a diagnosis of a benign versus malignant lesion. RESULTS: The accuracy using semiquantitative DCE-MRI parameters alone was 70.4% (0.693 area under the ROC curve, 57.5% sensitivity, 79.3% specificity). Adding absolute ADCs to dynamic contrast-enhanced MR data showed the higher diagnostic accuracy of 85.7% (0.873 area under the ROC curve, 85.0% sensitivity, 86.2% specificity). Moreover, the absolute ADCs differed significantly between the benign (mean [SD] ADC, 1.211 [0.32] * 10 mm/s) and malignant (mean [SD] ADC, 0.702 [0.28] * 10 mm/s) sinonasal tumors (P < 0.001). In addition, a significant difference was found between the ADC values of malignant and benign lesions in washout enhancement TICs (t = 7.039, P < 0.001). CONCLUSIONS: High-resolution DWI with ADC mapping significantly improved the diagnostic accuracy of dynamic contrast-enhanced sinonasal MRI at 3.0T. In addition, ADC values could distinguish benign lesions from malignant tumors in washout enhancement TICs. PMID- 27560027 TI - Imaging Microscopic Features of Keratoconic Corneal Morphology. AB - PURPOSE: To search for gold-standard histology indicators using alternative imaging modalities in keratoconic corneas. METHODS: Prospective observational case-control study. Fourteen keratoconic corneas and 20 normal corneas (10 in vivo healthy subjects and 10 ex vivo donor corneas) were examined. Images of corneas were taken by spectral domain optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) before keratoplasty. The same removed corneal buttons were imaged after keratoplasty with full-field optical coherence microscopy (FFOCM) and then fixed and sent for histology. Controls consisted of normal subjects imaged in vivo with IVCM and donor corneas imaged ex vivo with FFOCM. Corneal structural changes related to pathology were noted with each imaging modality. Cell density was quantified by manual cell counting. RESULTS: Keratoconus indicators (ie, epithelial thinning/thickening, cell shape changes, ferritin deposits, basement membrane anomalies, Bowman layer thinning, ruptures, interruptions, scarring, stromal modifications, and appearance of Vogt striae) were generally visible with all modalities. Additional features could be seen with FFOCM in comparison with gold-standard histology, particularly in the Bowman layer region, whereas the combination of SD-OCT plus IVCM detected 76% of those features detected in histology. Three-dimensional FFOCM imaging aided interpretation of two-dimensional IVCM and SD-OCT data. Basal epithelial cell and keratocyte densities were significantly lower in patients with keratoconus than those in normals (P < 0.0001). CONCLUSIONS: Structural and cellular assessment of the keratoconic cornea by means of either in vivo SD-OCT combined with IVCM or ex vivo FFOCM in both cross-sectional and en face views can detect as many keratoconus indicators as gold-standard histology. PMID- 27560028 TI - Role of Thyroxine in the Development of Keratoconus. AB - PURPOSE: Keratoconus (KC) is a corneal ectasia whose pathophysiology is still mostly unknown. We investigated whether thyroid gland dysfunction (TGD) is associated with the development of KC. METHODS: We first conducted an epidemiological study, examining the prevalence of TGD among patients with KC. Then, we compared tear thyroxine (T4) in TGD and immunohistochemical staining of its receptors (T4Rs) between patients with KC and controls. The significance of T4 for corneal metabolism was studied in organotypic tissue cultures from monkey corneas. RESULTS: We found that TGD prevalence among patients with KC is 13.6%, which is higher than its prevalence in the general population (about 2%). Tear T4 was higher in KC, and keratocyte T4Rs were elevated in KC compared with controls. Furthermore, core proteins such as collagen and cytokeratins were equally altered both in KC and in the cultured corneas substituted with T4. CONCLUSIONS: Our data implicate a crucial role of T4 in KC pathophysiology, which is most likely mediated by T4Rs. PMID- 27560029 TI - Unilateral Iris-Claw Intraocular Lens Implantation for Aphakia: A Paired-Eye Comparison. AB - PURPOSE: To perform a paired-eye comparison of secondary iris-claw intraocular lens (IOL) implantation for aphakia. METHODS: Retrospective, comparative, nonrandomized interventional case series of aphakic eyes, which underwent secondary iris-claw Artisan IOL (Ophtec BV) implantation for aphakia in one eye and no surgery (group 1) or cataract surgery (group 2) in the fellow eye. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent, central endothelial cell count (cECC), and complications were evaluated before surgery, and at yearly intervals up to 5 years. RESULTS: Thirty aphakic eyes implanted with the Artisan were included, and the fellow eyes served as controls. In group 1, postoperative logMAR UDVA and CDVA was significantly higher in the Artisan-implanted eyes (P < 0.01). In group 2, no differences were found in postoperative UDVA and postoperative CDVA between the Artisan-implanted eyes and the eyes that underwent cataract surgery throughout the follow-up (P >= 0.05). No statistically significant differences were found in postoperative spherical equivalent between the Artisan-implanted eyes and unoperated eyes or eyes that underwent cataract surgery (P >= 0.05). In group 1, cECC was significantly lower in the Artisan-implanted eyes [1973 +/- 822 vs. 2616 +/- 481 cells per square millimeter at 2 years (P < 0.01)] throughout the follow-up (P < 0.01). In group 2, cECC was not significantly lower in the Artisan-implanted eyes (P >= 0.05) [1934 +/- 689 vs. 2058 +/- 818 cells per square millimeter at 2 years (P = 0.67)]. CONCLUSIONS: Visual rehabilitation with secondary iris-claw IOL implantation in aphakic eyes without capsular support seems to be an effective and safe procedure. As expected, uncomplicated cataract surgery with posterior chamber IOL implantation showed lower endothelial cell count loss. Close monitoring of the corneal endothelium is mandatory. PMID- 27560030 TI - Prevention and Management of Pupil Block After Descemet Membrane Endothelial Keratoplasty. AB - PURPOSE: To assess frequency, associations, and outcomes of full air fill after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This retrospective study reviewed 368 consecutive DMEK cases performed to treat Fuchs dystrophy, bullous keratopathy, or failed keratoplasty. Primary outcomes were air bubble status, intraocular pressure, and incidence of pupil block and air reinjection. RESULTS: Using an air management algorithm, slit-lamp assessment 1 hour after DMEK identified complete air fill in 80/368 eyes (22%). This spontaneously resolved in 45 eyes. Air was removed from 35 eyes (9%). Eyes that required air removal were more likely to have occluded iridotomy than did eyes in which the full air fill spontaneously resolved (23% vs. 6.6%, respectively), P = 0.05. Although full air fill was more likely after DMEK combined with cataract surgery (P = 0.001), air removal was more likely after DMEK-only procedures (P = 0.01). Eyes that underwent air removal tended to have lower rebubble rates, although this did not reach statistical significance (P = 0.06). No cases of pupillary block glaucoma occurred, and full air fill did not significantly affect 6-month postoperative vision or endothelial cell density. CONCLUSIONS: A careful air management strategy successfully prevented pupil block in eyes that developed full air fill. DMEK-only procedures were more likely to require air removal than those combined with cataract surgery, which suggests that decreased zonular flexibility may prevent the air bubble from taking a more spherical shape and more easily allow occlusion of iridotomy. PMID- 27560031 TI - Biomechanical Properties of the Cornea Measured With the Dynamic Scheimpflug Analyzer in Young Healthy Adults. AB - PURPOSE: To investigate the biomechanical properties of the cornea using the dynamic Scheimpflug analyzer in young healthy adults. METHODS: This prospective cross-sectional population study included 944 eyes of 472 participants aged 20 to 40 years. Participants underwent ophthalmic investigations, including evaluation of biomechanical properties of the cornea using the dynamic Scheimpflug analyzer, manifest refraction, and measurements of keratometric values by autokeratometry, intraocular pressure (IOP) by noncontact tonometer, central corneal thickness (CCT) by ultrasound, and white-to-white distance by Scheimpflug tomography. Statistical analyses included determination of the reference interval with a bootstrapping method, linear quantile mixed-effects model, and Spearman correlation analysis between the corneal biomechanical parameters and other variables (age, manifest refraction spherical equivalent, CCT, IOP, white-to white, and keratometric values). RESULTS: The 90% CIs of all corneal biomechanical parameters demonstrated that the ranges of the 90% CIs for the reference data were almost identical with and without bootstrapping. Quantile regression to determine the fifth, 50th, and 95th percentiles of each corneal biomechanical parameter supported the findings from the nonparametric method with the 90% CIs. Correlation analysis showed significant correlations between the parameters and variables, but there was a relatively high Spearman correlation coefficient in the case of the correlations with the CCT and IOP. CONCLUSIONS: Using data from a large population of young healthy adults, we developed a database of normal values for multiple corneal biomechanical parameters obtained from the dynamic Scheimpflug analyzer. We conclude that the biomechanical properties of the cornea are influenced by the CCT and IOP. PMID- 27560032 TI - Dry Eye After Small Incision Lenticule Extraction and Femtosecond Laser-Assisted LASIK: Meta-Analysis. AB - PURPOSE: To compare postoperative ocular surface integrity and innervation between small incision lenticule extraction (SMILE) and femtosecond laser assisted laser in situ keratomileusis (FS-LASIK). METHODS: The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for prospective comparative studies. Trials meeting the selection criteria were quality appraised, and the data were extracted by 2 independent authors. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to compare dry eye examinations and corneal subbasal nerve density (SMILE-FS-LASIK). RESULTS: The study covered 5 trials. No significant difference was found in the Schirmer test score between both groups (WMD = -1.91 and 0.27; 95% CI, -5.02 to 1.20 and -0.99 to 1.54; P = 0.23 and 0.67 at 1- and 6-month follow-ups, respectively). Tear breakup time in the SMILE group significantly exceeded that in the FS-LASIK group (WMD = 0.65 and 1.14; 95% CI, 0.20-1.10 and 0.18-2.10; P = 0.004 and 0.02, at 1- and 6-month follow-ups, respectively). Ocular surface disease index scores were significantly better in the SMILE group 6 months postoperatively (WMD = -10.12, 95% CI, -16.07 to -4.18, P = 0.0008). No significant difference was found in tear osmolarity between both groups (WMD = 5.19 and -6.37; 95% CI, -17.15 to 6.76 and -22.74 to 10.00; P = 0.39 and 0.45 at 1- and 6-month follow-ups, respectively). Higher corneal sensitivity was observed in the SMILE group 1 and 6 months postoperatively (WMD = 11.35 and 3.49; 95% CI, 7.29-15.40 and 1.76-5.21; P < 0.00001 and <0.0001, at 1- and 6-month follow-ups, respectively). Corneal subbasal nerve density was also significantly higher in SMILE-treated eyes than it was in FS-LASIK-treated eyes 1 month postoperatively (WMD = 4.72, 95% CI, 1.10-8.34, P = 0.01). CONCLUSIONS: According to this meta analysis, the SMILE procedure has fewer negative impacts on the ocular surface and corneal innervation than does FS-LASIK. Furthermore, SMILE shows superiority over FS-LASIK by a exhibiting a lower risk of postoperative dry eye. PMID- 27560033 TI - Characterizing Contact Lens-Related Corneal Infiltrates: A Pilot Study. AB - PURPOSE: To document the time course and resolution of contact lens-related corneal infiltrative events (CIEs) comparing slit-lamp images with anterior segment ocular coherence tomography (AS-OCT) images. METHODS: Six silicone hydrogel (SiHy) soft contact lens (SCL) wearers presenting with newly diagnosed symptomatic CIEs were monitored with slit-lamp images, detailed drawings, and AS OCT until the resolution of the CIE. A final follow-up visit was completed 4 weeks after CIE resolution to determine whether scar formation was present. Positive controls were 2 SiHy SCL wearers with established (inactive) corneal scars, and negative controls were 2 SiHy SCL wearers with clear corneas. High- and low-contrast logMAR visual acuities were measured, and subjective symptom questionnaires were completed at all visits. RESULTS: Clinical signs, vision, and symptoms improved in tandem with the resolution of the CIEs as measured by imaging methods. Calibrated measures of infiltrate width from a slit-lamp biomicroscope appear to be similar to calibrated images from AS-OCT. CONCLUSIONS: Although further studies are needed to develop standardized procedures, AS-OCT can be a useful tool to characterize the development, progression, and resolution of corneal infiltrates as an objective measure of resolution and scar formation. PMID- 27560034 TI - Rare Case of Polymicrobial Keratitis With Balantidium coli. AB - PURPOSE: To report a rare case of polymicrobial keratitis due to Balantidium coli and gram-negative bacteria, Pseudomonas aeruginosa and Klebsiella pneumoniae, in a soft contact lens (CL) wearer. METHODS: We report a case of CL-related keratitis due to B. coli, P. aeruginosa, and K. pneumoniae. RESULTS: The culture of the corneal scrapings, the CL cleaning solution, and the CL revealed the growth of a rare ciliated parasite, B. coli, along with gram-negative bacteria, namely, P. aeruginosa and K. pneumoniae. The patient was successfully treated with topical broad-spectrum antibiotics and intravenous metronidazole. CONCLUSIONS: Polymicrobial keratitis has seldom been reported with B. coli as the causative agent. CL wear can be a risk factor for this infection. Treatment with topical antibiotics may not suffice, and the intravenous route of antiprotozoal drugs may be a useful adjunct. Increasing awareness, early diagnosis, and treatment may improve the final visual outcome. PMID- 27560035 TI - Comparison of Long-Term Outcomes of Visual Function and Endothelial Cell Survival After Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty Using Mixed-Effects Models. AB - PURPOSE: To compare the long-term outcomes of visual function and endothelial cell survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). METHODS: The cohort included 108 eyes from 97 patients who underwent primary PK and 85 eyes from 78 patients who underwent primary DSAEK at Miyata Eye Hospital in Japan. Uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), endothelial cell density, and four components from Fourier harmonic analysis of topography data (spherical component, regular astigmatism component, asymmetry component, and higher-order irregularity component) were retrospectively compared between PK and DSAEK at each time point for 5 years using mixed-effects models. Subgroup analyses were performed to compare the effect of PK and DSAEK on visual acuity. RESULTS: Average BSCVA was significantly better in the DSAEK group compared with that in the PK group both preoperatively and postoperatively. Subgroup analyses revealed that average changes in BSCVA from preoperative baseline in eyes with preoperative logarithm of the minimum angle of resolution BSCVA between 0.39 and 1.0 and between 1.3 and 2.0 were not significantly different between the PK and DSAEK groups at all postoperative time points. All components from Fourier harmonic analysis were significantly higher after PK than DSAEK at almost all postoperative time points. There were no significant differences in endothelial cell density between PK and DSAEK after 3 years. CONCLUSIONS: PK and DSAEK provide similar recovery of BSCVA and endothelial cell survival at 5 years after surgery. PMID- 27560036 TI - The thioredoxin MoTrx2 protein mediates reactive oxygen species (ROS) balance and controls pathogenicity as a target of the transcription factor MoAP1 in Magnaporthe oryzae. AB - We have shown previously that the transcription factor MoAP1 governs the oxidative response and is important for pathogenicity in the rice blast fungus Magnaporthe oryzae. To explore the underlying mechanism, we have identified thioredoxin MoTrx2 as a target of MoAP1 in M. oryzae. Thioredoxins are highly conserved 12-kDa oxidoreductase enzymes containing a dithiol-disulfide active site, and function as antioxidants against free radicals, such as reactive oxygen species (ROS). In yeast and fungi, thioredoxins are important for oxidative stress tolerance and growth. To study the functions of MoTrx2, we generated DeltaMotrx2 mutants that exhibit various defects, including sulfite assimilation, asexual and sexual differentiation, infectious hyphal growth and pathogenicity. We found that DeltaMotrx2 mutants possess a defect in the scavenging of ROS during host cell invasion and in the active suppression of the rice defence response. We also found that DeltaMotrx2 mutants display higher intracellular ROS levels during conidial germination, but lower peroxidase and laccase activities, which contribute to the attenuation in virulence. Given that the function of MoTrx2 overlaps that of MoAP1 in the stress response and pathogenicity, our findings further indicate that MoTrx2 is a key thioredoxin protein whose function is subjected to transcriptional regulation by MoAP1 in M. oryzae. PMID- 27560037 TI - The pretectal connectome in lamprey. AB - In vertebrates, the pretectum and optic tectum (superior colliculus in mammals) are visuomotor areas that process sensory information and shape motor responses. Whereas the tectum has been investigated in great detail, the pretectum has received far less attention. The present study provides a detailed analysis of the connectivity and neuronal properties of lamprey pretectal cells. The pretectum can be subdivided roughly into three areas based on cellular location and projection pattern: superficial, central, and periventricular. Three different types of pretectal cells could be distinguished based on neuronal firing patterns. One type, the rapid spike-inactivation cells, preferentially lie within the periventricular zone; the other cell types are distributed more generally. In terms of afferentation, the pretectum receives electro- and mechanoreceptive inputs in addition to retinal input. Histological data reveal that a large number of pretectal cells in the superficial and central areas extend dendrites into the optic tract, suggesting a predominant retinal influence even outside of the normal retinal terminal areas. The pretectum receives inhibitory input from the basal ganglia, and input from the pallium (cortex in mammals) and torus semicircularis. In addition, the pretectum is reciprocally connected with the thalamus, tectum, octavolateral area, and habenula. The main pretectal output is to the reticulospinal nuclei, and thus the pretectum indirectly affects the control of movement. Efference copies of some of this output are relayed to the thalamus and tectum. Overall, its extensive circuitry especially the reciprocal connectivity with other retinorecipient areas underlines the importance of the pretectum for sensory integration and visuomotor functions. J. Comp. Neurol. 525:753-772, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27560039 TI - From Gold Nanoseeds to Nanorods: The Microscopic Origin of the Anisotropic Growth. AB - Directly manipulating and controlling the size and shape of metal nanoparticles is a key step for their tailored applications. In this work, molecular dynamics simulations were applied to understand the microscopic origin of the asymmetric growth mechanism in gold nanorods. Different factors influencing the growth were selectively included in the models to unravel the role of the surfactants and ions. In the early stage of the growth, when the seed is only a few nanometers large, a dramatic symmetry breaking occurs as the surfactant layer preferentially covers the (100) and (110) facets, leaving the (111) facets unprotected. This anisotropic surfactant layer in turn promotes anisotropic growth with the less protected tips growing faster. When silver salt is added to the growth solution, the asymmetry of the facets is preserved, but the Br(-) concentration at the interface increases, resulting in increased surface passivation. PMID- 27560038 TI - Benefits of active middle ear implants in mixed hearing loss: Stapes versus round window. AB - OBJECTIVES/HYPOTHESIS: We compared the audiologic benefits of active middle ear implants with those of passive middle ear implants with hearing aids in mixed hearing loss, and also compared the outcomes of stapes vibroplasty with those of round window vibroplasty. STUDY DESIGN: Retrospective chart review. METHODS: Thirty-four patients with mixed hearing loss due to chronic otitis media were treated with a middle ear implant. Of these, 15 were treated with a passive middle ear implant (conventional ossiculoplasty with a partial ossicular replacement prosthesis), nine with an active middle ear implant coupling to the stapes, and 10 with an active middle ear implant coupling to the round window. Patients underwent pure-tone/free-field audiograms and speech discrimination tests before surgery and 6 months after surgery, and the results of these tests were compared. RESULTS: The active middle ear implant resulted in better outcomes than the passive middle ear implant with hearing aids at mid to high frequencies (P < .05). Patients who received either a stapes vibroplasty or a round window vibroplasty showed comparable hearing gain except at 8,000 Hz (48.9 dB vs. 31.0 dB, P < .05). Patients who received a stapes vibroplasty showed an improvement even in bone conduction at 1,000 Hz and 2,000 Hz (both P < .05). CONCLUSIONS: Active middle ear implantation could be a better option than treatment with passive middle ear implants with hearing aids for achieving rehabilitation in patients with mixed hearing loss. Vibroplasty via either oval window or round window stimulation shares similar good results. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1435-1441, 2017. PMID- 27560041 TI - No Conflict, No Interest. PMID- 27560040 TI - Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes. AB - Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current IK1, which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential IK1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that IK1 was substantially diminished in dystrophin deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels. PMID- 27560042 TI - Translation and evaluation of Chinese version of the symptom experience index. AB - Symptom assessment is crucial for patient care through the entire disease trajectory. Patients often experience multiple symptoms concurrently. The symptom experience index is reliable and valid as an instrument developed in the USA for assessing multiple symptoms and distress. The aim of the study was to translate and evaluate the Chinese version of the instrument in healthy adults and oncology patients. This is a psychometric study with a cross-sectional design. To ensure the semantic equivalence and content validity, an integrative translation method was employed to translate the English version into Chinese language. The participants were recruited during 2014 from a large university, two university affiliated hospitals and a community in Changchun, China. The Chinese version demonstrated high internal consistency, test-retest reliability and content validity. Construct validity was supported by factor analysis and significant differences of symptom experience scores between healthy and oncology groups. Participants' acceptance of the Chinese version and its ability to collect adequate data among Chinese population provided evidence for using this version among Chinese population. This study provided initial evidence to support the psychometric properties of the Chinese version. The Chinese version demonstrated adequate reliability and validity to assess multiple symptom experience by Chinese populations. PMID- 27560094 TI - Lack of household clustering of malaria in a complex humanitarian emergency: implications for active case detection. AB - BACKGROUND: Malaria contributes to elevated morbidity and mortality in populations displaced by conflict in tropical zones. In an attempt to reduce malaria transmission in an internally displaced persons (IDP) camp in eastern Democratic Republic of Congo (DRC), we tested a strategy of active case detection of household contacts of malaria cases. METHODS: Prospective community-based survey. RESULTS: From a convenience sample of 100 febrile patients under 5 years of age from the IDP camp presenting to a nearby clinic for management of a fever episode, 19 cases of uncomplicated malaria and 81 controls with non-malarial febrile illness (NFMI) were diagnosed. We engaged community health workers in the IDP camp to screen their household contacts for malaria using rapid diagnostic tests. We detected 29 cases of malaria through this active case-finding procedure. Household contacts of children with uncomplicated malaria were no more likely to have positive Plasmodium falciparum antigenemia than controls with NFMI (OR 0.89, 95% CI 0.33 to 2.4, p = 1.0), suggesting that malaria cases did not cluster at the household level. However, household contacts reporting mild symptoms at the time of community survey (headache, myalgia) had a higher odds of malaria than asymptomatic individuals (OR 14 (95% CI 4.2-48), p <= 0.001 and 18 (95% CI 5.9-54), p <= 0.001, respectively). CONCLUSION: Screening household contacts of malaria cases was not an efficient case-finding strategy in a Congolese IDP camp. Symptom-based screening may be a simpler and cost-effective method to identify individuals at increased risk of malaria for targeted screening and treatment in an IDP camp. PMID- 27560095 TI - Assessment of mutagenic, hematological and oxidative stress biomarkers in liver of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) in response to sublethal verapamil exposure. AB - The influx of pharmaceutical drugs and their metabolites have been reported to cause negative impact on aquatic biota. In this study, effects of long-term exposure of verapamil on mutagenic, hematological parameters and activities of the oxidative enzymes of Nile tilapia, Oreochromis niloticus were investigated for 60 days exposure at the concentrations of 0.29, 0.58 and 1.15 mg L-1 in the fish liver. The exposure resulted in significantly high (p < 0.05) micronuclei induction of peripheral blood cells at the peak on day 30 at 1.15 mg L-1. Compared with the control, there was significant increase (p < 0.05) in white blood cell counts and red blood cell distribution width (RDW), with a reduction in hemoglobin (Hb), red blood cell counts (RBCs), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) level as the concentration of the drug increased. The indices of oxidative stress biomarkers (lipid peroxidation and carbonyl protein) showed elevated level, depicting a positive correlation with both time and concentration. More so, the activity of energy related parameter (Na+ -K+- ATPase) in the tissue was significantly inhibited (p < 0.05) at the end of 60 days exposure period. Further, the activity of catalase (CAT) was inhibited while reduced glutathione (GSH) level was decreased in the liver tissue. There was increase in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) after 30 days at 0.29 mg L-1. The study demonstrated that prolonged exposure to verapamil at sublethal concentration can result in mutagenic effects and oxidative dysfunctions in O. niloticus. PMID- 27560096 TI - Brain trauma and autophagy: What flies and mice can teach us about conserved responses. AB - Drosophila models have been successfully used to identify many genetic components that affect neurodegenerative disorders. Recently, there has been a growing interest in identifying innate and environmental factors that influence the individual outcomes following traumatic brain injury (TBI). This includes both severe TBI and more subtle, mild TBI (mTBI), which is common in people playing contact sports. Autophagy, as a clearance pathway, exerts protective effects in multiple neurological disease models. In a recent publication, we highlighted the development of a novel repetitive mTBI system using Drosophila, which recapitulates several phenotypes associated with trauma in mammalian models. In particular, flies subjected to mTBI exhibit an acute impairment of the macroautophagy/autophagy pathway that is restored 1 wk following traumatic injury exposure. These phenotypes closely resemble temporary autophagy defects observed in a mouse TBI model. Through these studies, we also identified methods to directly assess autophagic responses in the fly nervous system and laid the groundwork for future studies designed to identify genetic, epigenetic and environmental factors that have an impact on TBI outcomes. PMID- 27560097 TI - Near-Infrared Photoinduced Coupling Reactions Assisted by Upconversion Nanoparticles. AB - We introduce nitrile imine-mediated tetrazole-ene cycloadditions (NITEC) in the presence of upconversion nanoparticles (UCNPs) as a powerful covalent coupling tool. When a pyrene aryl tetrazole derivative (lambdaabs, max =346 nm) and UCNPs are irradiated with near-infrared light at 974 nm, rapid conversion of the tetrazole into a reactive nitrile imine occurs. In the presence of an electron deficient double bond, quantitative conversion into a pyrazoline cycloadduct is observed under ambient conditions. The combination of NITEC and UCNP technology is used for small-molecule cycloadditions, polymer end-group modification, and the formation of block copolymers from functional macromolecular precursors, constituting the first example of a NIR-induced cycloaddition. To show the potential for in vivo applications, through-tissue experiments with a biologically relevant biotin species were carried out. Quantitative cycloadditions and retention of the biological activity of the biotin units are possible at 974 nm irradiation. PMID- 27560099 TI - [Persistent Symptoms after Carpal Tunnel Release: the Challenge of Preoperative Planning - a Case Report]. PMID- 27560098 TI - Perception of Hair Transplant for Androgenetic Alopecia. AB - Importance: Hair transplant is among the most common cosmetic services sought by men, with more than 11 000 procedures performed in 2014. Despite its growing popularity, the effect of hair transplant on societal perceptions of youth, attractiveness, or facets of workplace and social success is unknown. Objectives: To determine whether hair transplant improves observer ratings of age, attractiveness, successfulness, and approachability in men treated for androgenetic alopecia and to quantify the effect of hair transplant on each of these domains. Design, Setting, and Participants: A randomized controlled experiment was conducted from November 10 to December 6, 2015, using web-based surveys featuring photographs of men before and after hair transplant. One hundred twenty-two participants recruited through various social media platforms successfully completed the survey. Observers were shown 2 side-by-side images of each man and asked to compare the image on the left with the one on the right. Of 13 pairs of images displayed, 7 men had undergone a hair transplant procedure and 6 had served as controls. Observers evaluated each photograph using various metrics, including age, attractiveness, successfulness, and approachability. A multivariate analysis of variance was performed to understand the effect of hair transplant on observer perceptions. Planned posthypothesis testing was used to identify which variables changed significantly as a result of the transplant. Main Outcomes and Measures: Observer ratings of age (in number of years younger) and attractiveness, successfulness, and approachability (on a scale of 0 to 100; scores higher than 50 indicate a positive change). Results: Of the 122 participants in the survey, 58 were men (47.5%); mean (range) age was 27.1 (18 52) years. The initial multivariate analysis of variance revealed a statistically significant multivariate effect for transplant (Wilks lambda = 0.9646; P < .001). Planned posthypothesis analyses were performed to examine individual differences across the 4 domains. Findings determined with t tests showed a significant positive effect of hair transplant on observers' perceptions of age (mean [SD] number of years younger, 3.6 [2.9] years; P < .001), attractiveness (mean [SD] score, 58.5 [17.5]; P < .001), successfulness (mean [SD] score, 57.1 [17.1]; P = .008), and approachability (mean [SD] score, 59.2 [18.1]; P = .02). Conclusions and Relevance: Men were perceived as being younger and more attractive by casual observers after undergoing hair transplant. Participants also rated posttransplant faces as appearing more successful and approachable relative to their pretransplant counterparts. These aspects have been shown to play a substantial role in both workplace and social success, and these data demonstrate that hair transplant can improve ratings universally across all 4 domains. Level of Evidence: NA. PMID- 27560100 TI - Severe influenza in children: incidence and risk factors. AB - INTRODUCTION: The identification of factors that can predispose to the development of severe influenza is essential to enable the implementation of optimal prevention and control measures for vulnerable populations. AREAS COVERED: Unfortunately, data in the pediatric age group remain difficult to interpret. However, epidemiological data seem to suggest that the most severe influenza cases, those who are hospitalized, those who are admitted to the intensive care unit, and those who died, occur in children in the first 2 years of life and in school age patients. Expert commentary: Immaturity of the immune system, and in particular of the mechanisms that usually recognize influenza viruses and activate cytokine and chemokine responses to reduce viral replication, might explain the high hospitalization rate observed in the youngest patients. Some underlying chronic conditions favour the development of the severe cases, sometime leading to death, although both admission to the intensive care unit and death can occur in otherwise healthy subjects. PMID- 27560101 TI - Surgical Treatment for T4 Oropharyngeal Cancer. PMID- 27560102 TI - Archives of Environmental & Occupational Health: The little journal that could. PMID- 27560103 TI - Antenatal Diagnosis of a Large Immature Abdominal Wall Teratoma by 2D-3D Ultrasound Using HDlive and Magnetic Resonance Imaging. AB - We describe the first case of prenatally detected teratoma of the fetal abdomen wall using ultrasound and fetal magnetic resonance imaging (MRI). A heterogeneous mass, partly solid and cystic, originating from the anterior abdominal wall of the fetus close to an omphalocele sac was detected by means of 2D/3D ultrasound and MRI. Amniodrainage was performed and due to sign of impending fetal risk, an emergency Cesarean section was performed. A bulky, crumbly and bleeding tumoral mass was confirmed at delivery. Ligation of the supplying artery to the tumor was complicated by uncontrollable hemorrhage and early neonatal death. Pathology identified the tumor as an immature teratoma of the anterior fetal abdominal wall. 2D/3D ultrasound, especially using HDlive application and MRI demonstrated accurate detection and characterization of this congenital tumor. PMID- 27560104 TI - A commentary on 'generally representative is representative of none: pitfalls of IQ test standardization in multicultural settings' by A.B. Shuttleworth-Edwards. AB - We offer an appraisal of Professor Shuttleworth-Edwards's commentary (2016) on the extraordinary challenges of assessment of cognitive function in a culturally, educationally, racially, and linguistically diverse population. First, we discuss the purpose of using intelligence tests in South Africa and beyond in order to clarify the reference group on which norms will be based. Next, we discuss the psychometric consequences of Pearson's decisions to not adapt their measure of intellectual functioning to the cultural background of the majority of South Africans, and to use a population-matched normative sample in which the disadvantaged group is in the majority. We echo Professor Shuttleworth-Edwards's call for large-scale empirical studies of cognitive test performance in a multicultural context. We conclude the article by urging the entire community of neuropsychologists to hold test companies accountable to strict, ethical, and comprehensive standards for production of accurate and appropriate measurement of cognitive function. PMID- 27560105 TI - Multi-segmental movements as a function of experience in karate. AB - Karate is a martial art that partly depends on subjective scoring of complex movements. Principal component analysis (PCA)-based methods can identify the fundamental synergies (principal movements) of motor system, providing a quantitative global analysis of technique. In this study, we aimed at describing the fundamental multi-joint synergies of a karate performance, under the hypothesis that the latter are skilldependent; estimate karateka's experience level, expressed as years of practice. A motion capture system recorded traditional karate techniques of 10 professional and amateur karateka. At any time point, the 3D-coordinates of body markers produced posture vectors that were normalised, concatenated from all karateka and submitted to a first PCA. Five principal movements described both gross movement synergies and individual differences. A second PCA followed by linear regression estimated the years of practice using principal movements (eigenpostures and weighting curves) and centre of mass kinematics (error: 3.71 years; R2 = 0.91, P ? 0.001). Principal movements and eigenpostures varied among different karateka and as functions of experience. This approach provides a framework to develop visual tools for the analysis of motor synergies in karate, allowing to detect the multi-joint motor patterns that should be restored after an injury, or to be specifically trained to increase performance. PMID- 27560106 TI - Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide. PMID- 27560107 TI - The CALR exon 9 mutations are shared neoantigens in patients with CALR mutant chronic myeloproliferative neoplasms. PMID- 27560108 TI - Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis. AB - Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with 50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9% and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7% and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ?1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement. PMID- 27560111 TI - Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. AB - The landscape of additional chromosomal alterations (ACAs) and their impact in chronic myeloid leukemia, blast phase (CML-BP) treated with tyrosine kinase inhibitors (TKIs) have not been well studied. Here, we investigated a cohort of 354 CML-BP patients treated with TKIs. We identified +8, an extra Philadelphia chromosome (Ph), 3q26.2 rearrangement, -7 and isochromosome 17q (i(17q)) as the major-route changes with a frequency of over 10%. In addition, +21 and +19 had a frequency of over 5%. These ACAs demonstrated lineage specificity: +8, 3q26.2 rearrangement, i(17q) and +19 were significantly more common in myeloid BP, and 7 more common in lymphoid BP; +Ph and +21 were equally distributed between two groups. Pearson correlation analysis revealed clustering of common ACAs into two groups: 3q26.2 rearrangement, -7 and i(17q) formed one group, and other ACAs formed another group. The grouping correlated with risk stratification of ACAs in CML, chronic phase. Despite the overall negative prognostic impact of ACAs, stratification of ACAs into major vs minor-route changes provided no prognostic relevance in CML-BP. The emergence of 3q26.2 rearrangement as a major-route change in the TKI era correlated with a high frequency of ABL1 mutations, supporting a role for TKI resistance in the changing cytogenetic landscape in CML BP. PMID- 27560112 TI - Toll-like receptor signaling-deficient mice are easy mobilizers: evidence that TLR signaling prevents mobilization of hematopoietic stem/progenitor cells in HO 1-dependent manner. PMID- 27560114 TI - Defying Stereotypes with Nanodiamonds: Stable Primary Diamondoid Phosphines. AB - Direct unequal C-H bond difunctionalization of phosphorylated diamantane was achieved in high yield from the corresponding phosphonates. Reduction of the functionalized phosphonates provides access to novel primary and secondary alkyl/aryl diamantane phosphines. The prepared primary diamantyl phosphines are quite air stable compared to their adamantyl and especially alkyl or aryl analogues. This finding is corroborated by comparing the singly occupied molecular orbital energy levels of the corresponding phosphine radical cations obtained by density functional theory computations. PMID- 27560115 TI - Advice for New (and Seasoned) Faculty: Reprise. PMID- 27560113 TI - Rationale and efficacy of proteasome inhibitor combined with arsenic trioxide in the treatment of acute promyelocytic leukemia. AB - Arsenic trioxide (ATO) mediates PML-RARA (promyelocytic leukemia-retinoic acid receptor-alpha) oncoprotein degradation via the proteasome pathway and this degradation appears to be critical for achieving cure in acute promyeloytic leukemia (APL). We have previously demonstrated significant micro-environment mediated drug resistance (EMDR) to ATO in APL. Here we demonstrate that this EMDR could be effectively overcome by combining a proteasome inhibitor (bortezomib) with ATO. A synergistic effect on combining these two agents in vitro was noted in both ATO-sensitive and ATO-resistant APL cell lines. The mechanism of this synergy involved downregulation of the nuclear factor-kappaB pathway, increase in unfolded protein response (UPR) and an increase in reactive oxygen species generation in the malignant cell. We also noted that PML-RARA oncoprotein is effectively cleared with this combination in spite of proteasome inhibition by bortezomib, and that this clearance is mediated through a p62-dependent autophagy pathway. We further demonstrated that proteasome inhibition along with ATO had an additive effect in inducing autophagy. The beneficial effect of this combination was further validated in an animal model and in an on-going clinical trial. This study raises the potential of a non-myelotoxic proteasome inhibitor replacing anthracyclines in the management of high-risk and relapsed APL. PMID- 27560116 TI - Motivations and Expectations of Undergraduate Nursing Students Undertaking International Clinical Placements. AB - BACKGROUND: International clinical placements are common in preregistration nursing programs in Australian universities to enhance awareness of cultural needs and global health issues. Yet, little is known about the motivations and expectations of nursing students who choose to participate. METHOD: Using a qualitative exploratory design, individual semistructured interviews were undertaken with 52 preregistration final-year nursing students from four Western Australian universities 2 weeks prior to departure to the developing countries of Tanzania, Thailand, the Philippines, Cambodia, and India. Data were analyzed using thematic analysis. RESULTS: The interviews revealed that students were motivated by cultural inquisitiveness and a desire to help. They expected to gain cultural learning, to be challenged, to be fulfilled, to experience professional growth, and to feel gratitude. Developing an understanding of culture was a crucial outcome. CONCLUSION: By understanding the impetus and personal motivations of students, educators can guide students toward a more transformative experience whereby a more multicultural perspective on health care can be developed. [J Nurs Educ. 2016;55(9):487-494.]. PMID- 27560117 TI - Pursuing Improvement in Clinical Reasoning: Development of the Clinical Coaching Interactions Inventory. AB - BACKGROUND: Clinical coaching has been identified as a signature pedagogy in nursing education. Recent findings indicate that clinical coaching interactions in the clinical learning environment fail to engage students in the higher order thinking skills believed to promote clinical reasoning. METHOD: The Clinical Coaching Interactions Inventory (CCII) was based on evidence of supervisor questioning techniques, the Tanner clinical judgment model, Bloom's Taxonomy, and simulation evaluation tools. Content validity was established with expert assessment, student testing for clarity, and calculation of scale-content validity index/average (S-CVI/Ave). Reliability was established with Kuder Richardson Formula 20 (KR-20). RESULTS: CVI (S-CVI/Ave) was .91, and KR-20 was .70. The CCII identified differences in clinical coaching behaviors in university faculty supervisors and staff nurse preceptor supervisors. CONCLUSION: The CCII advances the measurement of clinical coaching interactions from qualitative to quantitative. Ultimately, results from use of this inventory may facilitate the design of prelicensure clinical coaching strategies that promote the improvement of students' clinical reasoning skill. [J Nurs Educ. 2016;55(9):495-504.]. PMID- 27560118 TI - Seeing Students Squirm: Nursing Students' Experiences of Bullying Behaviors During Clinical Rotations. AB - BACKGROUND: Bullying remains a troubling problem in the nursing profession. Nursing students may encounter bullying behavior in clinical settings. However, they may not be adequately prepared to recognize and handle bullying behavior when it occurs. This study's purpose was to gain a greater understanding of nursing students' experiences of bullying behaviors in the clinical setting. METHOD: Using a descriptive qualitative approach, eight focus groups were held with 56 undergraduate baccalaureate nursing students from four college campuses. Focus group data were coded and analyzed for themes. RESULTS: Four categories were identified: Bullying Behaviors, Rationale for Bullying, Response to Bullying, and Recommendations to Address Bullying. Each category and its corresponding themes are presented. CONCLUSION: Interventions for nurse educators to address the bullying of nursing students in clinical settings are presented. [J Nurs Educ. 2016;55(9):505-513.]. PMID- 27560119 TI - Enhancing Critical Thinking in Graduate Nursing Online Asynchronous Discussions. AB - BACKGROUND: Graduate nursing students in online courses often have limited success in developing the critical thinking (CT) skills essential for advanced roles. This study describes the use of complementary strategies in a graduate level nursing course to enhance CT in online discussions. METHOD: Using Paul and Elder's framework for understanding the components of CT, the authors designed an asynchronous online course using multiple strategies to promote CT. We used mixed methods to collect descriptive and numerical data and content and repeated measures analyses to identify changes in CT skills and student perceptions across the semester. RESULTS: CT scores increased significantly and aligned with students' perceived improvements in CT. CONCLUSION: Evidence of CT in online discussions increased significantly across the semester with the use of multiple instructional strategies and substantial student and faculty efforts. The findings are a useful benchmark for future studies comparing combinations of strategies to identify those most effective and least arduous. [J Nurs Educ. 2016;55(9):514-521.]. PMID- 27560120 TI - Self-Reflection of Video-Recorded High-Fidelity Simulations and Development of Clinical Judgment. AB - BACKGROUND: Nurse educators are increasingly using high-fidelity simulators to improve prelicensure nursing students' ability to develop clinical judgment. Traditionally, oral debriefing sessions have immediately followed the simulation scenarios as a method for students to connect theory to practice and therefore develop clinical judgment. Recently, video recording of the simulation scenarios is being incorporated. METHOD: This qualitative, interpretive description study was conducted to identify whether self-reflection on video-recorded high-fidelity simulation (HFS) scenarios helped prelicensure nursing students to develop clinical judgment. Tanner's clinical judgment model was the framework for this study. RESULTS: Four themes emerged from this study: Confidence, Communication, Decision Making, and Change in Clinical Practice. CONCLUSION: This study indicated that self-reflection of video-recorded HFS scenarios is beneficial for prelicensure nursing students to develop clinical judgment. [J Nurs Educ. 2016;55(9):522-527.]. PMID- 27560121 TI - Nursing Student Perceptions Regarding Simulation Experience Sequencing. AB - BACKGROUND: The use of simulated learning experiences (SLEs) have increased within nursing curricula with positive learning outcomes for nursing students. The purpose of this study is to explore nursing students' perceptions of their clinical decision making (CDM) related to the block sequencing of different patient care experiences, SLEs versus hospital-based learning experiences (HLEs). METHOD: A qualitative descriptive design used open-ended survey questions to generate information about the block sequencing of SLEs and its impact on nursing students' perceived CDM. RESULTS: Three themes emerged from the data: Preexperience Anxiety, Real-Time Decision Making, and Increased Patient Care Experiences. CONCLUSION: Nursing students identified that having SLEs prior to HLEs provided several benefits. Even when students preferred SLEs prior to HLEs, the sequence did not impact their CDM. This suggests that alternating block sequencing can be used without impacting the students' perceptions of their ability to make decisions. [J Nurs Educ. 2016;55(9):528-532.]. PMID- 27560122 TI - The e-Poster Conference: An Online Nursing Research Course Learning Activity. AB - BACKGROUND: Posters have become one of the most important types of scientific communication. This article describes an e-poster conference as an online learning activity for professional nursing students. METHOD: Research and evidence-based practice (EBP) project posters from colleagues across the country were placed on a university research course Web site, along with an evaluation tool and discussion prompts. During one semester, students experienced a range of activities focused on understanding research and EBP basic processes in preparation for evaluation and discussion of the layout and content of these e posters. RESULTS: From all accounts, the conference was rated as positive, providing nursing students with opportunities to (a) view studies and projects from a wider nursing science audience, (b) foster the development of important evaluation and communication skills, and (c) be exposed to evidence that could be translated into their practice. CONCLUSION: Other schools and organizations may adopt this e-poster conference activity to stimulate professional nurses' critical thinking ability. [J Nurs Educ. 2016;55(9):533-535.]. PMID- 27560123 TI - Second Life((r)) Virtual Learning in Public Health Nursing. AB - BACKGROUND: With limited available public health nursing clinical placements, nurse educators are challenged to create alternative learning experiences that engage students. METHOD: Nursing faculty developed three Second Life(r) virtual learning scenarios in family health, disaster preparedness, and home safety areas of interest as a supplement to clinical experiences for undergraduate senior nursing students in a public health nursing course. Student perceptions of their learning were evaluated by a survey and focus group. RESULTS: Although students perceived learning public health nursing knowledge, they were less likely to agree that the experience was as effective for learning about public health nursing when compared with on-site clinical experiences. CONCLUSION: The use of Second Life is an effective learning platform for teaching undergraduate nursing students public health nursing when clinical experiences are difficult to obtain. Nursing faculty need to ensure technological challenges are addressed and that scenarios are realistic, and engage students through interactive collaboration. [J Nurs Educ. 2016;55(9):536-540.]. PMID- 27560124 TI - PsyConnect: Constructing Layered Engagement for Optimal Learning in Clinical Education. AB - BACKGROUND: The increasing volume of nursing students placed in shrinking numbers of clinical sites has resulted in clinical overcrowding in behavioral care settings. Overcrowding has resulted in the deterioration of the clinical teaching and learning experience for students, faculty, and nurses. PsyConnect is a layered, multiplatform engagement learning experience that uses multiple teaching methods to increase student engagement, reduce inpatient overcrowding, maximize learning opportunities, and improve teaching and learning experiences. METHOD: PsyConnect was implemented in a baccalaureate mental health nursing course during one term. Investigators surveyed students, faculty, and nurses who attended campus simulation. Data analysis included measures of central tendency and Pearson correlation coefficient. RESULTS: Setting rotations, clinical checklists, off-unit learning modules, and simulation with staff nurses improved educational experiences, as reported by students, faculty, and participating nurses. CONCLUSION: The PsyConnect evaluation suggested that layered, multiplatform, engagement-based learning addressed critical barriers to high-quality, clinical education. [J Nurs Educ. 2016;55(9):541-543.]. PMID- 27560125 TI - A Unique Clinical Experience for RN-to-BSN Students: Providing Farm Safety Education. PMID- 27560126 TI - Surface Engineered Protein Nanoparticles With Hyaluronic Acid Based Multilayers For Targeted Delivery Of Anticancer Agents. AB - Layer-by-layer (LbL) technique was employed to modify the surface of doxorubicin (Dox)-loaded bovine serum albumin (BSA) nanoparticles using hyaluronic acid (HA) to enable targeted delivery to overexpressed CD44 receptors in metastatic breast cancer cells. LbL technique offers a versatile approach to modify the surface of colloidal nanoparticles without any covalent modification. Dox-loaded BSA (Dox Ab) nanoparticles optimized for their size, zeta potential, and drug encapsulation efficiency were prepared by modified desolvation technique. The cellular uptake and cytotoxicity of the LbL coated Dox Ab nanoparticles were analyzed in CD44 overexpressing breast cancer cell line MDA-MB-231. Nanoparticles with HA as the final layer (Dox Ab HA) showed maximum cellular uptake in MDA-MB 231 cells owing to the CD44 receptor-mediated endocytosis and hence, exhibited more cytotoxicity as compared to free Dox. Further, luciferase-transfected MDA-MB 231 cells were used to induce tumor in BALB/c female nude mice to enable whole body tumor imaging. The mice were imaged before and after Dox treatment to visualize the tumor growth. The in vivo biodistribution of Dox Ab HA nanoparticles in nude mice showed maximum accumulation in tumor, and importantly, better tumor reduction in comparison with free Dox, thus paving the way for improved drug delivery into tumors. PMID- 27560127 TI - Does Replica Exchange with Solute Tempering Efficiently Sample Abeta Peptide Conformational Ensembles? AB - We have applied replica exchange with solute tempering (REST) molecular dynamics to study a short fragment of the Abeta peptide, Abeta25-35, in water and a much larger system incorporating two Abeta10-40 peptides binding to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer. As a control, we used traditional replica exchange molecular dynamics (REMD) applied to the same systems. Our objective was to assess the practical utility of REST simulations. Taken together, our results suggest four conclusions. First, compared to REMD, the number of replicas in REST simulations can be reduced four to five times without affecting the temperature range or compromising an efficient random walk of REST replicas over temperatures. Second, although overall REST produces much fewer conformational states than REMD, there is no substantial difference in the collection of unique states for the wild-type replica in REST and REMD, especially for the system featuring Abeta peptides binding to the lipid bilayer. Third, we performed a thorough comparison of REST and REMD equilibrium conformational ensembles, including thermal averages and probability distributions. REST reproduces REMD data extremely well for the system of Abeta peptides binding to the DMPC lipid bilayer. The agreement between REST and REMD equilibrium sampling of Abeta25-35 in water is less perfect, but it improves with addition of new REST simulations. Surprisingly, REST demonstrates much better convergence for the system featuring ordered peptides binding to lipid bilayer rather than for a small unstructured peptide solvated in water. Fourth, REST delivers its full computational advantage over REMD when applied to peptides interacting with lipid bilayers. For peptides solvated in water, REST does not appear to offer computational gain but may make replica simulations practically feasible due to a lower requirement for parallel computing environments. Our study is expected to facilitate wider application of REST in biomolecular simulations. PMID- 27560128 TI - Epigenetic Regulation of Caveolin-1 Gene Expression in Lung Fibroblasts. AB - Fibrotic disorders are associated with tissue accumulation of fibroblasts. We recently showed that caveolin (Cav)-1 gene suppression by a profibrotic cytokine, transforming growth factor (TGF)-beta1, contributes to fibroblast proliferation and apoptosis resistance. Cav-1 has been shown to be constitutively suppressed in idiopathic pulmonary fibrosis (IPF), but mechanisms for this suppression are incompletely understood. We hypothesized that epigenetic processes contribute to Cav-1 down-regulation in IPF lung fibroblasts, and after fibrogenic stimuli. Cav 1 expression levels, DNA methylation status, and histone modifications associated with the Cav-1 promoter were examined by PCR, Western blots, pyrosequencing, or chromatin immunoprecipitation assays in IPF lung fibroblasts, normal fibroblasts after TGF-beta1 stimulation, or in murine lung fibroblasts after bleomycin injury. Methylation-specific PCR demonstrated methylated and unmethylated Cav-1 DNA copies in all groups. Despite significant changes in Cav-1 expression, no changes in DNA methylation were observed in CpG islands or CpG island shores of the Cav-1 promoter by pyrosequencing of lung fibroblasts from IPF lungs, in response to TGF-beta1, or after bleomycin-induced murine lung injury, when compared with respective controls. In contrast, the association of Cav-1 promoter with the active histone modification mark, H3 lysine 4 trimethylation, correlated with Cav-1 down-regulation in activated/fibrotic lung fibroblasts. Our data indicate that Cav-1 gene silencing in lung fibroblasts is actively regulated by epigenetic mechanisms that involve histone modifications, in particular H3 lysine 4 trimethylation, whereas DNA methylation does not appear to be a primary mechanism. These findings support therapeutic strategies that target histone modifications to restore Cav-1 expression in fibroblasts participating in pathogenic tissue remodeling. PMID- 27560130 TI - How the launch of a new journal in 1904 may have changed the relationship between psychology and philosophy. AB - Recent research has used networks of scholarly journal articles to investigate the intellectual structure of the discipline of psychology from the later 1880s to the early 1920s. Here, instead, we examined the networks of philosophical journals that were closely aligned with psychology-The Monist, Philosophical Review, and The Journal of Philosophy, Psychology, and Scientific Methods-between 1890 and 1913. We discovered that, although the first 2 of these journals published a great deal of psychologically relevant material up to 1903, material of that sort seemed to evaporate after the launch of the third journal in 1904. It was not so much that material migrated from the old journals to the new one. It was rather that the new journal was able to attract new trends in American philosophical psychology, while interest in traditional approaches seemed to dry up. The result was that psychology moved into a new and expansive era, while America philosophy was left somewhat destabilized as it attempted to reconfigure its disciplinary identity. (PsycINFO Database Record PMID- 27560131 TI - A Discovered Ducal Seal Does Not Belong to the Incorporation Charter for the City of Krakow Solving the Mystery Using Genetic Methods. AB - The Incorporation Charter for the city of Krakow, the former capital of Poland, is one of the most valuable documents stored in the National Archives in Krakow. The document, which was written in 1257 on parchment, grants Krakow the Magdeburg rights and regulates its legal, statutory, economic and settlement-related aspects. The Charter was placed in the National Register of the Memory of the World UNESCO programme in 2014. A ducal seal, considered to be the lost seal detached from the Incorporation Charter, was found in the sphragistic collection after nearly 500 years. Unfortunately, it was uncertain whether the seal in question was indeed the missing part of the document. The aim of the study presented below was to solve this mystery. For this purpose, the parchment on which the Incorporation Charter was written was compared with the fragment of the parchment attached to the discovered seal. The study involved the analysis of selected mitochondrial DNA sequences and additional analysis at the level of nuclear DNA using microsatellite markers in the form of 11 STR (Short Tandem Repeat) loci, to identify the species and individual whose skin had been used to make the parchment. This analysis revealed that seal and parchment was from different individuals and thereby discovered that the seal was never a part of the Incorporation Charter. The study is further an example of informative DNA preservation in cultural heritage objects. PMID- 27560129 TI - Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. AB - The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain-Barre syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of "TORCH" viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication. PMID- 27560132 TI - Food Environments around American Indian Reservations: A Mixed Methods Study. AB - OBJECTIVES: To describe the food environments experienced by American Indians living on tribal lands in California. METHODS: Geocoded statewide food business data were used to define and categorize existing food vendors into healthy, unhealthy, and intermediate composite categories. Distance to and density of each of the composite food vendor categories for tribal lands and nontribal lands were compared using multivariate linear regression. Quantitative results were concurrently triangulated with qualitative data from in-depth interviews with tribal members (n = 24). RESULTS: After adjusting for census tract-level urbanicity and per capita income, results indicate there were significantly fewer healthy food outlets per square mile for tribal areas compared to non-tribal areas. Density of unhealthy outlets was not significantly different for tribal versus non-tribal areas. Tribal members perceived their food environment negatively and reported barriers to the acquisition of healthy food. CONCLUSIONS: Urbanicity and per capita income do not completely account for disparities in food environments among American Indians tribal lands compared to nontribal lands. This disparity in access to healthy food may present a barrier to acting on the intention to consume healthy food. PMID- 27560133 TI - The Impact of Services on Economic Complexity: Service Sophistication as Route for Economic Growth. AB - Economic complexity reflects the amount of knowledge that is embedded in the productive structure of an economy. By combining tools from network science and econometrics, a robust and stable relationship between a country's productive structure and its economic growth has been established. Here we report that not only goods but also services are important for predicting the rate at which countries will grow. By adopting a terminology which classifies manufactured goods and delivered services as products, we investigate the influence of services on the country's productive structure. In particular, we provide evidence that complexity indices for services are in general higher than those for goods, which is reflected in a general tendency to rank countries with developed service sector higher than countries with economy centred on manufacturing of goods. By focusing on country dynamics based on experimental data, we investigate the impact of services on the economic complexity of countries measured in the product space (consisting of both goods and services). Importantly, we show that diversification of service exports and its sophistication can provide an additional route for economic growth in both developing and developed countries. PMID- 27560134 TI - FTO Obesity Risk Variants Are Linked to Adipocyte IRX3 Expression and BMI of Children - Relevance of FTO Variants to Defend Body Weight in Lean Children? AB - BACKGROUND: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. AIM: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. RESULTS: Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. CONCLUSION: One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children. PMID- 27560135 TI - Precursor-Directed Mutational Biosynthesis Facilitates the Functional Assignment of Two Cytochromes P450 in Thiostrepton Biosynthesis. AB - Side-ring-modified thiostrepton (TSR) derivatives that vary in their quinaldic acid (QA) substitution possess more potent biological activities and better pharmaceutical properties than the parent compound. In this work, we sought to introduce fluorine onto C-7' or C-8' of the TSR QA moiety via precursor-directed mutational biosynthesis to obtain new TSR variants. Unexpectedly, instead of the target product, the exogenous chemical feeding of 7-F-QA into the DeltatsrT mutant strain resulted in a unique TSR analog with an incomplete side-ring structure and an unoxidized QA moiety (1). Accordingly, two cytochrome P450 genes, tsrP and tsrR, were in-frame deleted to elucidate the candidate responsible for the monooxidation of the QA moiety in TSR. The unfluorinated analog of compound 1 that was thus isolated from DeltatsrP (2) and the abolishment of TSR production in DeltatsrR revealed not only the biosynthetic logic of the TSR side-ring but also the essential checkpoint in TSR maturation before macro-ring closure. PMID- 27560136 TI - Innovative Flow Cytometry Allows Accurate Identification of Rare Circulating Cells Involved in Endothelial Dysfunction. AB - INTRODUCTION: Although rare, circulating endothelial and progenitor cells could be considered as markers of endothelial damage and repair potential, possibly predicting the severity of cardiovascular manifestations. A number of studies highlighted the role of these cells in age-related diseases, including those characterized by ectopic calcification. Nevertheless, their use in clinical practice is still controversial, mainly due to difficulties in finding reproducible and accurate methods for their determination. METHODS: Circulating mature cells (CMC, CD45-, CD34+, CD133-) and circulating progenitor cells (CPC, CD45dim, CD34bright, CD133+) were investigated by polychromatic high-speed flow cytometry to detect the expression of endothelial (CD309+) or osteogenic (BAP+) differentiation markers in healthy subjects and in patients affected by peripheral vascular manifestations associated with ectopic calcification. RESULTS: This study shows that: 1) polychromatic flow cytometry represents a valuable tool to accurately identify rare cells; 2) the balance of CD309+ on CMC/CD309+ on CPC is altered in patients affected by peripheral vascular manifestations, suggesting the occurrence of vascular damage and low repair potential; 3) the increase of circulating cells exhibiting a shift towards an osteoblast-like phenotype (BAP+) is observed in the presence of ectopic calcification. CONCLUSION: Differences between healthy subjects and patients with ectopic calcification indicate that this approach may be useful to better evaluate endothelial dysfunction in a clinical context. PMID- 27560137 TI - Genetic Variation of Methylenetetrahydrofolate Reductase (MTHFR) and Thymidylate Synthase (TS) Genes Is Associated with Idiopathic Recurrent Implantation Failure. AB - The one-carbon metabolism pathway disorder was important role in successful pregnancy. The MTHFR and TS protein were crucial factor in one-carbon metabolism. To investigate the association between recurrent implantation failure (RIF) and enzymes in the one-carbon metabolism pathway. A total of 120 women diagnosed with RIF and 125 control subjects were genotyped for MTHFR 677C>T, 1298A>C, TSER 2R/3R and TS 1494del/ins by a polymerase chain reaction-restriction fragment length polymorphism assay. According to the gene-gene combination analysis, the MTHFR 677/MTHFR 1298 (TT/AA) and MTHFR 677/TS 1494 (TT/6bp6bp) genetic combinations were associated with relatively higher risks [adjusted odds ratio (AOR), 2.764; 95% CI, 1.065-7.174; P = 0.037 and AOR, 3.186; 95% CI, 1.241-8.178; P = 0.016] in RIF patients compared to the CC/AA (MTHFR 677/MTHFR 1298) and TT/6bp6bp (MTHFR 677/TS 1494) combinations, respectively. The results suggested that the combined MTHFR 677/MTHFR 1298 genotype might be associated with increased risk of RIF. To the best of our knowledge, this study is the first to elucidate the potential association of MTHFR, TS and TSER polymorphisms with RIF risk in Korean patients. PMID- 27560138 TI - Control Strategies for the DAB Based PV Interface System. AB - This paper presents an interface system based on the Dual Active Bridge (DAB) converter for Photovoltaic (PV) arrays. Two control strategies are proposed for the DAB converter to harvest the maximum power from the PV array. The first strategy is based on a simple PI controller to regulate the terminal PV voltage through the phase shift angle of the DAB converter. The Perturb and Observe (P&O) Maximum Power Point Tracking (MPPT) technique is utilized to set the reference of the PV terminal voltage. The second strategy presented in this paper employs the Artificial Neural Network (ANN) to directly set the phase shift angle of the DAB converter that results in harvesting maximum power. This feed-forward strategy overcomes the stability issues of the feedback strategy. The proposed PV interface systems are modeled and simulated using MATLAB/SIMULINK and the EMTDC/PSCAD software packages. The simulation results reveal accurate and fast response of the proposed systems. The dynamic performance of the proposed feed forward strategy outdoes that of the feedback strategy in terms of accuracy and response time. Moreover, an experimental prototype is built to test and validate the proposed PV interface system. PMID- 27560139 TI - Frugal Droplet Microfluidics Using Consumer Opto-Electronics. AB - The maker movement has shown how off-the-shelf devices can be combined to perform operations that, until recently, required expensive specialized equipment. Applying this philosophy to microfluidic devices can play a fundamental role in disseminating these technologies outside specialist labs and into industrial use. Here we show how nanoliter droplets can be manipulated using a commercial DVD writer, interfaced with an Arduino electronic controller. We couple the optical setup with a droplet generation and manipulation device based on the "confinement gradients" approach. This device uses regions of different depths to generate and transport the droplets, which further simplifies the operation and reduces the need for precise flow control. The use of robust consumer electronics, combined with open source hardware, leads to a great reduction in the price of the device, as well as its footprint, without reducing its performance compared with the laboratory setup. PMID- 27560140 TI - Correction: Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis. AB - [This corrects the article DOI: 10.1371/journal.pone.0154107.]. PMID- 27560141 TI - Effects of a Family-Based Childhood Obesity Treatment Program on Parental Weight Status. AB - OBJECTIVE: The aim of this study was to investigate the prevalence of overweight/obesity among parents of children entering childhood obesity treatment and to evaluate changes in the parents' weight statuses during their child's treatment. METHODS: The study included parents of 1,125 children and adolescents aged 3-22 years, who were enrolled in a multidisciplinary childhood obesity treatment program. At baseline, weight and height of the parents were obtained by self-reported information and parental body mass index (BMI) was calculated. Weight and height of the children were measured in the clinic and BMI standard deviation scores were calculated. Furthermore, anthropometric data from parents of 664 children were obtained by telephone interview after a mean of 2.5 years of treatment (ranging 16 days to 7 years), and changes in parental BMI were analyzed. RESULTS: Data on changes in BMI were available in 606 mothers and 479 fathers. At baseline, the median BMI of the mothers was 28.1 kg/m2 (range: 16.9 66.6), and the median BMI of the fathers was 28.9 kg/m2 (range: 17.2-48.1). Seventy percent of the mothers and 80% of the fathers were overweight or obese at the time of their child's treatment initiation. Both the mothers and fathers lost weight during their child's treatment with a mean decrease in BMI in the mothers of 0.5 (95% CI: 0.2-0.8, p = 0.0006) and in the fathers of 0.4 (95% CI: 0.2-0.6, p = 0.0007). Of the overweight/obese parents, 60% of the mothers and 58% of the fathers lost weight during their child's treatment. CONCLUSION: There is a high prevalence of overweight/obesity among parents of children entering childhood obesity treatment. Family-based childhood obesity treatment with a focus on the child has a positive effect on parental BMI with both mothers and fathers losing weight. TRIAL REGISTRATION: ClinicalTrials.gov NCT00928473. PMID- 27560142 TI - Thermoregulation of Meningococcal fHbp, an Important Virulence Factor and Vaccine Antigen, Is Mediated by Anti-ribosomal Binding Site Sequences in the Open Reading Frame. AB - During colonisation of the upper respiratory tract, bacteria are exposed to gradients of temperatures. Neisseria meningitidis is often present in the nasopharynx of healthy individuals, yet can occasionally cause severe disseminated disease. The meningococcus can evade the human complement system using a range of strategies that include recruitment of the negative complement regulator, factor H (CFH) via factor H binding protein (fHbp). We have shown previously that fHbp levels are influenced by the ambient temperature, with more fHbp produced at higher temperatures (i.e. at 37 degrees C compared with 30 degrees C). Here we further characterise the mechanisms underlying thermoregulation of fHbp, which occurs gradually over a physiologically relevant range of temperatures. We show that fHbp thermoregulation is not dependent on the promoters governing transcription of the bi- or mono-cistronic fHbp mRNA, or on meningococcal specific transcription factors. Instead, fHbp thermoregulation requires sequences located in the translated region of the mono-cistronic fHbp mRNA. Site-directed mutagenesis demonstrated that two anti-ribosomal binding sequences within the coding region of the fHbp transcript are involved in fHbp thermoregulation. Our results shed further light on mechanisms underlying the control of the production of this important virulence factor and vaccine antigen. PMID- 27560144 TI - Correction: Staged Models for Interdisciplinary Research. AB - [This corrects the article DOI: 10.1371/journal.pone.0157261.]. PMID- 27560143 TI - Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier Protein-Tethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus. AB - C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-beta tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-beta tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate. To address the molecular details of substrate specificity, we determined the crystal structures of SgcE6 and SgcC at 1.66 and 2.63 A resolution, respectively. SgcE6 shares a similar beta barrel fold with the class I HpaC-like flavin reductases. A flexible loop near the active site of SgcE6 plays a role in FAD binding, likely by providing sufficient space to accommodate the AMP moiety of FAD, when compared to that of FMN-utilizing homologues. SgcC shows structural similarity to a few other known FADH2-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. The crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate. PMID- 27560145 TI - Characterization of Promiscuous Binding of Phosphor Ligands to Breast-Cancer-Gene 1 (BRCA1) C-Terminal (BRCT): Molecular Dynamics, Free Energy, Entropy and Inhibitor Design. AB - Inhibition of the protein-protein interaction (PPI) mediated by breast-cancer gene 1 C-terminal (BRCT) is an attractive strategy to sensitize breast and ovarian cancers to chemotherapeutic agents that induce DNA damage. Such inhibitors could also be used for studies to understand the role of this PPI in DNA damage response. However, design of BRCT inhibitors is challenging because of the inherent flexibility associated with this domain. Several studies identified short phosphopeptides as tight BRCT binders. Here we investigated the thermodynamic properties of 18 phosphopeptides or peptide with phosphate mimic and three compounds with phosphate groups binding to BRCT to understand promiscuous molecular recognition and guide inhibitor design. We performed molecular dynamics (MD) simulations to investigate the interactions between inhibitors and BRCT and their dynamic behavior in the free and bound states. MD simulations revealed the key role of loops in altering the shape and size of the binding site to fit various ligands. The mining minima (M2) method was used for calculating binding free energy to explore the driving forces and the fine balance between configuration entropy loss and enthalpy gain. We designed a rigidified ligand, which showed unfavorable experimental binding affinity due to weakened enthalpy. This was because it lacked the ability to rearrange itself upon binding. Investigation of another phosphate group containing compound, C1, suggested that the entropy loss can be reduced by preventing significant narrowing of the energy well and introducing multiple new compound conformations in the bound states. From our computations, we designed an analog of C1 that introduced new intermolecular interactions to strengthen attractions while maintaining small entropic penalty. This study shows that flexible compounds do not always encounter larger entropy penalty, compared with other more rigid binders, and highlights a new strategy for inhibitor design. PMID- 27560147 TI - The Crotylation Way to Glycosphingolipids: Synthesis of Analogues of KRN7000. AB - A synthesis of glycosphingolipids that centers on the reaction of O- and C glycosyl crotylstannanes and relatively simple lipid aldehydes is described. The modularity of this strategy and versatility of the crotylation products make this an attractive approach to diverse, highly substituted libraries. The methodology is applied to analogues of the potent imunostimulatory glycolipid KRN7000, including O-, methylene-, and fluoromethine-linked isosteres with diastereomeric ceramide segments and 2-amido substitutes. PMID- 27560148 TI - Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability. AB - Our understanding of the role of new neurons in learning and encoding new information has been largely based on studies of new neurons in the mammalian dentate gyrus and olfactory bulb - brain regions that may be specialized for learning. Thus the role of new neurons in regions that serve other functions has yet to be fully explored. The song system provides a model for studying new neuron function in brain regions that contribute differently to song learning, song auditory discrimination, and song motor production. These regions subserve learning as well as long-term storage of previously learned information. This review examines the differences between learning-based and activity-based retention of new neurons and explores the potential contributions of new neurons to behavioral stability in the song motor production pathway. PMID- 27560146 TI - Spatial Disassociation of Disrupted Functional Connectivity for the Default Mode Network in Patients with End-Stage Renal Disease. AB - PURPOSE: To investigate the aberrant functional connectivity of the default mode network (DMN) in patients with end-stage renal disease (ESRD) and their clinical relevance. MATERIALS AND METHODS: Resting-state functional MRI data were collected from 31 patients with ESRD (24 men, 24-61 years) and 31 age- and gender matched healthy controls (HCs, 21 men, 26-61years). A whole-brain seed-based functional connectivity analysis of these collected R-fMRI data was performed by locating the seeds in the posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC) to investigate the functional connectivity of the posterior and anterior DMN over the whole brain, respectively. RESULTS: Compared to the HCs, the patients exhibited significantly decreased functional connectivity with the PCC in the left middle temporal gyrus, the right anterior cingulate gyrus, and the bilateral medial superior frontal gyrus. For the vmPFC seed, only the right thalamus showed significantly decreased functional connectivity in the patients with ESRD compared to HCs. Interestingly, functional connectivity between the PCC and right medial superior frontal gyrus exhibited a significantly positive correlation with the hemoglobin level in the patients. CONCLUSION: Our findings suggest a spatially specific disruption of functional connectivity in the DMN in patients with ESRD, thereby providing novel insights into our understanding of the neurophysiology mechanism that underlies the disease. PMID- 27560149 TI - Body Composition within the First 3 Months: Optimized Correction for Length and Correlation with BMI at 2 Years. AB - BACKGROUND/AIMS: Although early infant growth has implications for future health, body composition reference data in infancy are limited. The aim of this study was to describe reference data for fat mass (FM) and fat-free mass (FFM) corrected for length (L) within the first 3 months and to evaluate if these measures predict the body mass index (BMI) at 2 years. METHODS: Term infants had air displacement plethysmography performed at birth (n = 1,063) and approximately 2 months later (n = 922, between 49 and 86 days). Age- and sex-specific reference data were generated for FM, FFM, FM/L3 and FFM/L2 and compared with BMI at 2 years. RESULTS: FM/L3 and FFM/L2 were the optimal indices independent of length. In the first 3 months, mean FM/L3 increased (males, from 2.7 to 5.9 kg/m3; females, from 3.2 to 6.1 kg/m3), whereas FFM/L2 remained relatively stable (males, from 11.8 to 12.7 kg/m2; females, from 12.8 to 12.1 kg/m2). The odds of a BMI Z-score >=2 at 2 years increased with increasing FM (OR 2.7, 95% CI 1.97-3.7) and weight (OR 2.27, 95% CI 1.64-3.13) Z-scores at 2 months. CONCLUSIONS: FM/L3 and FFM/L2 provide length-independent measures of FM and FFM in infancy. During the first 3 months, there is an increase in FM/L3, but not in FFM/L2. The weight Z-score at 2 months is as good at predicting BMI at 2 years as body composition parameters. (c) 2016 S. Karger AG, Basel. PMID- 27560152 TI - Lymph Node Fine-Needle Cytology: Beyond Flow Cytometry. AB - Lymph node (LN) fine-needle cytology (FNC) coupled with flow cytometry immunophenotyping provides relevant information for the diagnosis of non-Hodgkin lymphoma (NHL). Numerous studies have shown FNC samples to be suitable for different molecular procedures; in this review, some of the molecular procedures most commonly employed for NHL are briefly described and evaluated in this perspective. Fluorescence in situ hybridization and chromogenic in situ hybridization are briefly described. Polymerase chain reaction (PCR)-based assays are used to identify and quantify mutations and translocations, namely immunoglobulin (IGH) and T-cell receptor rearrangements by clonality testing and IGVH somatic hypermutations either by Sanger sequencing, single-strand conformational polymorphisms or RT-PCR strategies. High-throughput technologies (HTT) encompass numerous and different diagnostic tools that share the capacity of multiple molecular investigation and sample processing in a fast and reproducible manner. HTT includes gene expression profiling, comparative genomic hybridization, single-nucleotide polymorphism arrays and next-generation sequencing technologies. A brief description of these tools and their potential application to LN FNC is reported. The challenge for FNC will be to achieve new knowledge and apply new technologies to FNC, exploiting its own basic qualities. PMID- 27560150 TI - HIV-Infected Children Have Lower Frequencies of CD8+ Mucosal-Associated Invariant T (MAIT) Cells that Correlate with Innate, Th17 and Th22 Cell Subsets. AB - Mucosal-associated invariant T cells (MAIT) are innate T cells restricted by major histocompatibility related molecule 1 (MR1) presenting riboflavin metabolite ligands derived from microbes. Specificity to riboflavin metabolites confers MAIT cells a broad array of host-protective activity against gram negative and -positive bacteria, mycobacteria, and fungal pathogens. MAIT cells are present at low levels in the peripheral blood of neonates and gradually expand to relatively abundant levels during childhood. Despite no anti-viral activity, MAIT cells are depleted early and irreversibly in HIV infected adults. Such loss or impaired expansion of MAIT cells in HIV-positive children may render them more susceptible to common childhood illnesses and opportunistic infections. In this study we evaluated the frequency of MAIT cells in perinatally HIV infected children, their response to antiretroviral treatment and their associations with HIV clinical status and related innate and adaptive immune cell subsets with potent antibacterial effector functions. We found HIV+ children between ages 3 to 18 years have significantly decreased CD8+ MAIT cell frequencies compared to uninfected healthy children. Remarkably, CD8 MAIT levels gradually increased with antiretroviral therapy, with greater recovery when treatment is initiated at a young age. Moreover, diminished CD8+ MAIT cell frequencies are associated with low CD4:CD8 ratios and elevated sCD14, suggesting a link with HIV disease progression. Last, CD8+ MAIT cell levels tightly correlate with other antibacterial and mucosa-protective immune subsets, namely, neutrophils, innate-like T cells, and Th17 and Th22 cells. Together these findings suggest that low frequencies of MAIT cells in HIV positive children are part of a concerted disruption to the innate and adaptive immune compartments specialized in sensing and responding to pathogenic or commensal bacteria. PMID- 27560151 TI - Transcriptome Characterization of Dendrolimus punctatus and Expression Profiles at Different Developmental Stages. AB - The pine moth Dendrolimus punctatus (Walker) is a common insect pest that confers serious damage to conifer forests in south of China. Extensive physiology and ecology studies on D. punctatus have been carried out, but the lack of genetic information has limited our understanding of the molecular mechanisms behind its development and resistance. Using RNA-seq approach, we characterized the transcriptome of this pine moth and investigated its developmental expression profiles during egg, larval, pupal, and adult stages. A total of 107.6 million raw reads were generated that were assembled into 70,664 unigenes. More than 30% unigenes were annotated by searching for homology in protein databases. To better understand the process of metamorphosis, we pairwise compared four developmental phases and obtained 17,624 differential expression genes. Functional enrichment analysis of differentially expressed genes showed positive correlation with specific physiological activities of each stage, and these results were confirmed by qRT-PCR experiments. This study provides a valuable genomic resource of D. punctatus covering all its developmental stages, and will promote future studies on biological processes at the molecular level. PMID- 27560153 TI - Mucosal Schwann Cell Hamartoma in Colorectal Mucosa: A Rare Benign Lesion That Resembles Gastrointestinal Neuroma. PMID- 27560154 TI - Assessment of the toxic potential of engineered metal oxide nanomaterials using an acellular model: citrated rat blood plasma. AB - Citrated Sprague-Dawley rat blood plasma was used as a biologically relevant exposure medium to assess the acellular toxic potential of two metal oxide engineered nanomaterials (ENMs), zinc oxide (nZnO), and cerium oxide (nCeO2). Plasma was incubated at 37 degrees C for up to 48 h with ENM concentrations ranging between 0 and 200 mg/L. The degree of ENM-induced oxidation was assessed by assaying for reactive oxygen species (ROS) levels using dichlorofluorescein (DCF), pH, ferric reducing ability of plasma (FRAP), lipase activity, malondialdehyde (MDA), and protein carbonyls (PC). Whereas previous in vitro studies showed linear-positive correlations between ENM concentration and oxidative damage, our results suggested that low concentrations were generally pro-oxidant and higher concentrations appeared antioxidant or protective, as indicated by DCF fluorescence trends. nZnO and nCeO2 also affected pH in a manner dependent on concentration and elemental composition; higher nZnO concentrations maintained a more alkaline pH, while nCeO2 tended to decrease pH. No other biomarkers of oxidative damage (FRAP, MDA, PC, lipase activity) showed changes at any ENM concentration or time-point tested. Differential dissolution of the two ENMs was also observed, where as much as ~31.3% of nZnO was instantaneously dissolved to Zn2+ and only negligible nCeO2 was degraded. The results suggest that the direct oxidative potential of nZnO and nCeO2 in citrated rat blood plasma is low, and that a physiological or immune response is needed to generate appreciable damage biomarkers. The data also highlight the need for careful consideration when selecting a model for assessing ENM toxicity. PMID- 27560155 TI - Changes in the craniofacial complex and alveolar bone height of young adults: Applications to dental medicine. AB - The few studies on craniofacial complex changes in adults have reported contradictory findings. The aim of this study was to radiographically evaluate changes in the craniofacial complex and alveolar bone height of young adults over a 4-year period. This prospective study included 82 young adults (62 men; mean age, 19.0 +/- 0.8 years; 20 women; mean age, 18.8 +/- 0.9 years). Three radiographic examinations were performed longitudinally: the first (T0) was conducted at the start of the study, the second (T1) was conducted 2 years later, and the third (T2) was conducted at the end of the study period. As part of these examinations, lateral cephalograms, maxillary and mandibular anterior periapical radiographs, and bilateral posterior bitewing radiographs were obtained. During the 4-year follow-up period, all linear cephalometric measurements were significantly greater in men than in women. The amount of increase in the anterior facial height between T1 and T2 was lower in women than in men (P = 0.029). The rate of uprighting of the upper incisors was lower in men than in women over time (P = 0.020). The apex of the nose moved inferiorly between T0 and T2 (P = 0.006). The average overall change in the alveolar bone height was 0.27 mm and the yearly change was 0.07 mm over the 4-year period (P< 0.001). Significant changes in the skeletal, dental, and soft tissue, as well as, natural changes in alveolar bone, occur in young adults over time. Clin. Anat. 29:1011 1017, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27560156 TI - Decreased Risk of Radiation Pneumonitis With Coincident Concurrent Use of Angiotensin-converting Enzyme Inhibitors in Patients Receiving Lung Stereotactic Body Radiation Therapy. AB - OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade >=2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT). METHODS: We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014. We reviewed pretreatment and posttreatment medication profiles to document use of ACEi, angiotensin receptor blockers, bronchodilators, aspirin, PDE-5 inhibitors, nitrates, and endothelin receptor antagonists. Pneumonitis was graded posttreatment based on Common Terminology Criteria for Adverse Events Version 4.0. Univariate and multivariate analysis was performed and time to development of pneumonitis was evaluated by the Kaplan-Meier method. RESULTS: A total of 189 patients were evaluated with a median follow-up of 24.8 months. The overall 1 year rate of symptomatic pneumonitis was 13.2%. The 1-year rate of symptomatic pneumonitis was 4.2% for ACEi users versus 16.3% in nonusers (P=0.03). On univariate analysis, the odds of developing grade 2 or greater pneumonitis were significantly lower for patients on ACEi (P=0.03). On multivariate analysis, after controlling for clinicopathologic characteristics and dosimetric endpoints, there was a significant association between ACEi use and decreased risk of clinical pneumonitis (P=0.04). Angiotensin receptor blockers or other bronchoactive medications did not show significant associations with development of pneumonitis. CONCLUSIONS: Incidental concurrent use of ACEi demonstrated efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung SBRT. PMID- 27560157 TI - Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer? AB - OBJECTIVE: The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence. METHODS: A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers. RESULTS: One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005). CONCLUSIONS: Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias. PMID- 27560158 TI - Children's attitudes toward interaction with an unfamiliar peer with complex communication needs: comparing high- and low-technology devices. AB - This study examined the attitudes of children with typical development towards an unfamiliar peer with complex communication needs using augmentative and alternative communication (AAC) systems. Specifically, the study aimed to compare attitudes when the peer used mobile technology (i.e., iPad(c)1 ) with an AAC specific application (Proloquo2GoTM 2 ) versus a low-technology communication board. A within-group crossover design was utilized involving 78 children. Half of the participants (i.e., Group 1) viewed Video 1 of an unfamiliar peer with complex communication needs in a scripted communication interaction using an iPad with Proloquo2Go followed by Video 2 of the same interaction using a communication board. The other half of the participants (Group 2) viewed these videos in the reverse sequence. The Communication Aid/Device Attitudinal Questionnaire (CADAQ) was completed after watching each video. Results indicated that both groups were more positive towards Video 1 (iPad with Prologuo2Go) on certain dimensions of the CADAQ. The results are discussed and recommendations for future research provided. PMID- 27560159 TI - Exfoliation of WS2 in the semiconducting phase using a group of lithium halides: a new method of Li intercalation. AB - Lithium halide assisted high yield synthesis of few layers of 2H phase semiconducting WS2 in organic solvents is reported. A group of lithium halides (LiCl, LiBr and LiI) has been employed for the first time to intercalate WS2 by using Li, followed by mild sonication to exfoliate in dispersive polar solvents. In contrast to the n-butyllithium (n-BuLi) assisted exfoliation method, which yields only the metallic 1T phase on prolonged reaction (3-7 days) at higher temperatures, the proposed exfoliation method produces only semiconducting 2H WS2 in a much shorter time (5 minute sonication). A very high yield of 19 mg ml(-1) has been obtained using LiI as an exfoliating agent due to its lower lattice energy compared to other alkali halides and the smaller size of the cation. Detailed microscopy and spectroscopic characterization reveals exfoliation of few layered WS2 with stoichiometric composition. Absorption and emission characteristics of the 2D WS2 layer exhibit a characteristic band edge and quantum confined transitions. As a proof-of-concept, we have successfully demonstrated photodetector devices comprising solution proccessed p-WS2/n-Si heterojunctions, which behave as diodes with a high rectification ratio (>10(2)) exhibiting a broad band photoresponse over the entire visible region. PMID- 27560161 TI - Comparison of Vitamin D Levels in Patients with and without Acne: A Case-Control Study Combined with a Randomized Controlled Trial. AB - BACKGROUND: Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin disease; however, the association with vitamin D remains unclear. OBJECTIVES: We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation. METHODS: This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months. RESULTS: Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency. LIMITATIONS: Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne. CONCLUSIONS: Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions. PMID- 27560160 TI - Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei. AB - BACKGROUND: Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors. METHODOLOGY/PRINCIPAL FINDINGS: We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge. CONCLUSIONS/SIGNIFICANCE: Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages. PMID- 27560162 TI - Poor compliance with adjuvant chemotherapy use associated with poorer survival in patients with rectal cancer: An NCDB analysis. AB - BACKGROUND: National Comprehensive Cancer Network treatment guidelines for patients with locally advanced rectal cancer include neoadjuvant chemoradiation followed by total mesorectal excision and adjuvant chemotherapy. The objective of the current study was to examine the rate of adjuvant chemotherapy and associated survival in patients with stage II/III rectal cancer. METHODS: The 2006 to 2011 National Cancer Data Base was queried for patients with AJCC clinical stage II/III rectal cancer who underwent neoadjuvant chemoradiation and surgical resection. A mixed effects multivariable logistic regression identified factors associated with the receipt of adjuvant chemotherapy. A mixed effects Cox proportional hazards model was used to estimate the adjusted effect of receiving adjuvant therapy on 5-year overall survival (OS). RESULTS: A total of 14,742 patients were included; 68% of the cohort did not receive adjuvant chemotherapy. When controlled for clinical stage of disease, patients who were aged >70 years, had a higher comorbidity score, and had a pathologic complete response had lower odds of receiving adjuvant therapy. There was a 22-fold difference in the risk adjusted rate of adjuvant therapy use among hospitals (3.1%-67.7%). Adjuvant therapy was associated with increased 5-year OS when controlled for patient factors, stage of disease, and pathologic response (hazard ratio, 0.65; 95% confidence interval, 0.59-0.71). The greatest survival benefit was noted among patients who achieved a pathologic complete response (hazard ratio, 0.40; 95% confidence interval, 0.23-0.67). CONCLUSIONS: There is poor compliance to National Comprehensive Cancer Network guidelines for adjuvant chemotherapy in patients with locally advanced rectal cancer after neoadjuvant chemoradiation and surgery. Adjuvant therapy appears to be independently associated with improved OS regardless of stage of disease, pathologic response, and patient factors. The greatest survival benefit was observed in patients who were complete responders. Age and comorbidities were found to be significantly associated with nonreceipt of adjuvant therapy. Improved rehabilitation and physical conditioning may improve the odds of patients receiving adjuvant therapy. Cancer 2017;52-61. (c) 2016 American Cancer Society. PMID- 27560165 TI - Bifunctional Ag/C3N4.5 composite nanobelts for photocatalysis and antibacterium. AB - Multiple functions can be achieved in carbon nitride-based composite nanomaterials by tuning their components and structures. Here, we report on a large-scale synthesis of novel bifunctional Ag/C3N4.5 composite nanobelts (CNBs) with efficient photocatalytic and antibacterial activity. The Ag/C3N4.5 CNBs were synthesized in high yield by a two-step route including a homogeneous precipitation process and a subsequent calcination treatment. The structural, morphological, compositional, and spectroscopic characterizations revealed that the Ag/C3N4.5 CNBs are composed of N-deficient melem ultrathin nanobelts and crystalline Ag nanoparticles attached to the surface of the nanobelts with good contact. The band gap of the Ag/C3N4.5 CNBs is determined to be about 3.04 eV. The efficient photocatalytic and antibacterial activities of the composite nanomaterials are verified by testing the degradation of Rhodamine B (RhB) and the inhibition zone to bacterium E. coli. The work provides a facile route to bifunctional carbon nitride-based composites with potential applications in the fields of the environment and biology. PMID- 27560164 TI - Novel Centromeric Loci of the Wine and Beer Yeast Dekkera bruxellensis CEN1 and CEN2. AB - The wine and beer yeast Dekkera bruxellensis thrives in environments that are harsh and limiting, especially in concentrations with low oxygen and high ethanol. Its different strains' chromosomes greatly vary in number (karyotype). This study isolates two novel centromeric loci (CEN1 and CEN2), which support both the yeast's autonomous replication and the stable maintenance of plasmids. In the sequenced genome of the D. bruxellensis strain CBS 2499, CEN1 and CEN2 are each present in one copy. They differ from the known "point" CEN elements, and their biological activity is retained within ~900-1300 bp DNA segments. CEN1 and CEN2 have features of both "point" and "regional" centromeres: They contain conserved DNA elements, ARSs, short repeats, one tRNA gene, and transposon-like elements within less than 1 kb. Our discovery of a miniature inverted-repeat transposable element (MITE) next to CEN2 is the first report of such transposons in yeast. The transformants carrying circular plasmids with cloned CEN1 and CEN2 undergo a phenotypic switch: They form fluffy colonies and produce three times more biofilm. The introduction of extra copies of CEN1 and CEN2 promotes both genome rearrangements and ploidy shifts, with these effects mediated by homologous recombination (between circular plasmid and genome centromere copy) or by chromosome breakage when integrated. Also, the proximity of the MITE-like transposon to CEN2 could translocate CEN2 within the genome or cause chromosomal breaks, so promoting genome dynamics. With extra copies of CEN1 and CEN2, the yeast's enhanced capacities to rearrange its genome and to change its gene expression could increase its abilities for exploiting new and demanding niches. PMID- 27560166 TI - Bioactivity and Osseointegration of PEEK Are Inferior to Those of Titanium: A Systematic Review. AB - Polyetheretherketone (PEEK) has been suggested as an alternative to replace titanium as a dental implant material. However, PEEK's bioactivity and osseointegration are debatable. This review has systematically analyzed studies that have compared PEEK (or PEEK-based) implants with titanium implants so that its feasibility as a possible replacement for titanium can be determined. The focused question was: "Are the bioactivity and osseointegration of PEEK implants comparable to or better than titanium implants?" Using the key words "dental implant," "implant," "polyetheretherketone," "PEEK," and "titanium" in various combinations, the following databases were searched electronically: PubMED/MEDLINE, Embase, Google Scholar, ISI Web of Knowledge, and Cochrane Database. 5 in vitro and 4 animal studies were included in the review. In 4 out of 5 in vitro studies, titanium exhibited more cellular proliferation, angiogenesis, osteoblast maturation, and osteogenesis compared to PEEK; one in vitro study observed comparable outcomes regardless of the implant material. In all animal studies, uncoated and coated titanium exhibited a more osteogenic behavior than did uncoated PEEK, while comparable bone-implant contact was observed in HA-coated PEEK and coated titanium implants. Unmodified PEEK is less osseoconductive and bioactive than titanium. Furthermore, the majority of studies had multiple sources of bias; hence, in its unmodified form, PEEK is unsuitable to be used as dental implant. Significantly more research and long-term trials must focus on improving the bioactivity of PEEK before it can be used as dental implant. More comparative animal and clinical studies are warranted to ascertain the potential of PEEK as a viable alternative to titanium. PMID- 27560167 TI - Dielectric relaxation of polymers: segmental dynamics under structural constraints. AB - In this article we review the recent polymer literature where dielectric spectroscopy has been used to investigate the segmental dynamics of polymers under the constraints produced by self-structuring. Specifically, we consider three cases: (i) semicrystalline polymers, (ii) segregated block-copolymers, and (iii) asymmetric miscible polymer blends. In these three situations the characteristics of the dielectric relaxation associated with the polymer segmental dynamics are markedly affected by the constraints imposed by the corresponding structural features. After reviewing in detail each of the polymer systems, the most common aspects are discussed in the context of the use of dielectric relaxation as a sensitive tool for analyzing structural features in nanostructured polymer systems. PMID- 27560169 TI - High-resolution 3D analysis of mouse small-intestinal stroma. AB - Here we detail a protocol for whole-mount immunostaining of mouse small intestinal villi that can be used to generate high-resolution 3D images of all gut cell types, including blood and lymphatic vessel cells, neurons, smooth muscle cells, fibroblasts and immune cells. The procedure describes perfusion, fixation, dissection, immunostaining, mounting, clearing, confocal imaging and quantification, using intestinal vasculature as an example. As intestinal epithelial cells prevent visualization with some antibodies, we also provide an optional protocol to remove these cells before fixation. In contrast to alternative current techniques, our protocol enables the entire villus to be visualized with increased spatial resolution of cell location, morphology and cell-cell interactions, thus allowing for easy quantification of phenotypes. The technique, which takes 7 d from mouse dissection to microscopic examination, will be useful for researchers who are interested in most aspects of intestinal biology, including mucosal immunology, infection, nutrition, cancer biology and intestinal microbiota. PMID- 27560168 TI - Evaluation of the PPAR-gamma Agonist Pioglitazone in Mild Asthma: A Double-Blind Randomized Controlled Trial. AB - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. METHODS: Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency's reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. RESULTS: There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). CONCLUSIONS: We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma. TRIAL REGISTRATION: ClinicalTrials.gov NCT01134835. PMID- 27560170 TI - A high-yield double-purification proteomics strategy for the identification of SUMO sites. AB - The small ubiquitin-like modifier (SUMO) is a protein modifier that is post translationally coupled to thousands of lysines in more than a thousand proteins. An understanding of which lysines are modified by SUMO is critical in unraveling its function as a master regulator of all nuclear processes, as well as its involvement in diseases such as cancer. Here we describe a protocol for the lysine-deficient (K0) method for efficient identification of SUMOylated lysines by mass spectrometry (MS). To our knowledge, the K0 method is the only currently available method that can routinely identify >1,000 SUMO sites in mammalian cells under standard growth conditions. The K0 strategy relies on introducing a His10 tagged SUMO wherein all lysines have been substituted to arginines. Lysine deficiency renders the SUMO immune to digestion by the endoproteinase Lys-C, which in turn allows for stringent and high-yield tandem purification through the His10 tag. In addition, the His10-tagged SUMO also contains a C-terminal Q87R mutation, which accommodates generation of SUMO-site peptides with a QQTGG mass remnant after digestion with trypsin. This remnant possesses a unique mass signature and readily generates diagnostic ions in the fragment ion scans, which increases SUMO-site identification confidence. The K0 method can be applied in any mammalian cell line or in any model system that allows for integration of the K0-SUMO construct. From the moment of cell lysis, the K0 method takes ~7 d to perform. PMID- 27560171 TI - Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. AB - High-throughput sequencing of mRNA (RNA-seq) has become the standard method for measuring and comparing the levels of gene expression in a wide variety of species and conditions. RNA-seq experiments generate very large, complex data sets that demand fast, accurate and flexible software to reduce the raw read data to comprehensible results. HISAT (hierarchical indexing for spliced alignment of transcripts), StringTie and Ballgown are free, open-source software tools for comprehensive analysis of RNA-seq experiments. Together, they allow scientists to align reads to a genome, assemble transcripts including novel splice variants, compute the abundance of these transcripts in each sample and compare experiments to identify differentially expressed genes and transcripts. This protocol describes all the steps necessary to process a large set of raw sequencing reads and create lists of gene transcripts, expression levels, and differentially expressed genes and transcripts. The protocol's execution time depends on the computing resources, but it typically takes under 45 min of computer time. HISAT, StringTie and Ballgown are available from http://ccb.jhu.edu/software.shtml. PMID- 27560172 TI - Routine in vitro culture of P. falciparum gametocytes to evaluate novel transmission-blocking interventions. AB - The prevention of parasite transmission from the human host to the mosquito has been recognized as a vital tool for malaria eradication campaigns. However, transmission-blocking antimalarial drug and/or vaccine discovery and development is currently hampered by the expense and difficulty of producing mature Plasmodium falciparum gametocytes in vitro-the parasite stage responsible for mosquito infection. Current protocols for P. falciparum gametocyte culture usually require complex parasite synchronization and addition of stimulating and/or inhibitory factors, and they may not have demonstrated the essential property of mosquito infectivity. This protocol details all the steps required for reliable P. falciparum gametocyte production and highlights common factors that influence culture success. The protocol can be completed in 15 d, and particular emphasis is placed upon operating a gametocyte culture facility on a continuous cycle. In addition, we show how functionally viable gametocytes can be used to evaluate transmission-blocking drugs both in a field setting and at high throughput (HTP) for drug discovery. PMID- 27560173 TI - Generation of kidney organoids from human pluripotent stem cells. AB - The human kidney develops from four progenitor populations-nephron progenitors, ureteric epithelial progenitors, renal interstitial progenitors and endothelial progenitors-resulting in the formation of maximally 2 million nephrons. Until recently, the reported methods differentiated human pluripotent stem cells (hPSCs) into either nephron progenitor or ureteric epithelial progenitor cells, consequently forming only nephrons or collecting ducts, respectively. Here we detail a protocol that simultaneously induces all four progenitors to generate kidney organoids within which segmented nephrons are connected to collecting ducts and surrounded by renal interstitial cells and an endothelial network. As evidence of functional maturity, proximal tubules within organoids display megalin-mediated and cubilin-mediated endocytosis, and they respond to a nephrotoxicant to undergo apoptosis. This protocol consists of 7 d of monolayer culture for intermediate mesoderm induction, followed by 18 d of 3D culture to facilitate self-organizing renogenic events leading to organoid formation. Personnel experienced in culturing hPSCs are required to conduct this protocol. PMID- 27560174 TI - Multiplexed high-content analysis of mitochondrial morphofunction using live-cell microscopy. AB - Mitochondria have a central role in cellular (patho)physiology, and they display a highly variable morphology that is probably coupled to their functional state. Here we present a protocol that allows unbiased and automated quantification of mitochondrial 'morphofunction' (i.e., morphology and membrane potential), cellular parameters (size, confluence) and nuclear parameters (number, morphology) in intact living primary human skin fibroblasts (PHSFs). Cells are cultured in 96-well plates and stained with tetramethyl rhodamine methyl ester (TMRM), calcein-AM (acetoxy-methyl ester) and Hoechst 33258. Next, multispectral fluorescence images are acquired using automated microscopy and processed to extract 44 descriptors. Subsequently, the descriptor data are subjected to a quality control (QC) algorithm based upon principal component analysis (PCA) and interpreted using univariate, bivariate and multivariate analysis. The protocol requires a time investment of ~4 h distributed over 2 d. Although it is specifically developed for PHSFs, which are widely used in preclinical research, the protocol is portable to other cell types and can be scaled up for implementation in high-content screening. PMID- 27560175 TI - A simple method for imaging axonal transport in aging neurons using the adult Drosophila wing. AB - There is growing interest in the link between axonal cargo transport and age associated neuronal dysfunction. The study of axonal transport in neurons of adult animals requires intravital or ex vivo imaging approaches, which are laborious and expensive in vertebrate models. We describe simple, noninvasive procedures for imaging cargo motility within axons using sensory neurons of the translucent Drosophila wing. A key aspect is a method for mounting the intact fly that allows detailed imaging of transport in wing neurons. Coupled with existing genetic tools in Drosophila, this is a tractable system for studying axonal transport over the life span of an animal and thus for characterization of the relationship between cargo dynamics, neuronal aging and disease. Preparation of a sample for imaging takes ~5 min, with transport typically filmed for 2-3 min per wing. We also document procedures for the quantification of transport parameters from the acquired images and describe how the protocol can be adapted to study other cell biological processes in aging neurons. PMID- 27560176 TI - Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. AB - Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver and pancreas into self-assembling 3D structures that we have termed 'organoids'. We provide a detailed protocol that describes how to grow adult mouse and human liver and pancreas organoids, from cell isolation and long-term expansion to genetic manipulation in vitro. Liver and pancreas cells grow in a gel-based extracellular matrix (ECM) and a defined medium. The cells can self-organize into organoids that self-renew in vitro while retaining their tissue-of-origin commitment, genetic stability and potential to differentiate into functional cells in vitro (hepatocytes) and in vivo (hepatocytes and endocrine cells). Genetic modification of these organoids opens up avenues for the manipulation of adult stem cells in vitro, which could facilitate the study of human biology and allow gene correction for regenerative medicine purposes. The complete protocol takes 1-4 weeks to generate self-renewing 3D organoids and to perform genetic manipulation experiments. Personnel with basic scientific training can conduct this protocol. PMID- 27560177 TI - Preparation of supramolecular hydrogel-enzyme hybrids exhibiting biomolecule responsive gel degradation. AB - Hydrogelators are small, self-assembling molecules that form supramolecular nanofiber networks that exhibit unique dynamic properties. Development of supramolecular hydrogels that degrade in response to various biomolecules could potentially be used for applications in areas such as drug delivery and diagnostics. Here we provide a synthetic procedure for preparing redox-responsive supramolecular hydrogelators that are used to create hydrogels that degrade in response to oxidizing or reducing conditions. The synthesis takes ~2-4 d, and it can potentially be carried out in parallel to prepare multiple hydrogelator candidates. This described solid-phase peptide synthesis protocol can be used to produce previously described hydrogelators or to construct a focused molecular library to efficiently discover and optimize new hydrogelators. In addition, we describe the preparation of redox-responsive supramolecular hydrogel-enzyme hybrids that are created by mixing aqueous solutions of hydrogelators and enzymes, which requires 2 h for completion. The resultant supramolecular hydrogel enzyme hybrids exhibit gel degradation in response to various biomolecules, and can be rationally designed by connecting the chemical reactions of the hydrogelators with enzymatic reactions. Gel degradation in response to biomolecules as triggers occurs within a few hours. We also describe the preparation of hydrogel-enzyme hybrids arrayed on flat glass slides, enabling high-throughput analysis of biomolecules such as glucose, uric acid, lactate and so on by gel degradation, which is detectable by the naked eye. The protocol requires ~6 h to prepare the hydrogel-enzyme hybrid array and to complete the biomolecule assay. PMID- 27560178 TI - Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes. AB - In morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles. This protocol describes the design and execution of experiments using Cell Painting, which is a morphological profiling assay that multiplexes six fluorescent dyes, imaged in five channels, to reveal eight broadly relevant cellular components or organelles. Cells are plated in multiwell plates, perturbed with the treatments to be tested, stained, fixed, and imaged on a high-throughput microscope. Next, an automated image analysis software identifies individual cells and measures ~1,500 morphological features (various measures of size, shape, texture, intensity, and so on) to produce a rich profile that is suitable for the detection of subtle phenotypes. Profiles of cell populations treated with different experimental perturbations can be compared to suit many goals, such as identifying the phenotypic impact of chemical or genetic perturbations, grouping compounds and/or genes into functional pathways, and identifying signatures of disease. Cell culture and image acquisition takes 2 weeks; feature extraction and data analysis take an additional 1-2 weeks. PMID- 27560179 TI - Physician Associate and General Practitioner Consultations: A Comparative Observational Video Study. AB - BACKGROUND: Physician associates, known internationally as physician assistants, are a mid-level practitioner, well established in the United States of America but new to the United Kingdom. A small number work in primary care under the supervision of general practitioners, where they most commonly see patients requesting same day appointments for new problems. As an adjunct to larger study, we investigated the quality of the patient consultation of physician associates in comparison to that of general practitioners. METHOD: We conducted a comparative observational study using video recordings of consultations by volunteer physician associates and general practitioners with consenting patients in single surgery sessions. Recordings were assessed by experienced general practitioners, blinded to the type of the consulting practitioner, using the Leicester Assessment Package. Assessors were asked to comment on the safety of the recorded consultations and to attempt to identify the type of practitioner. Ratings were compared across practitioner type, alongside the number of presenting complaints discussed in each consultation and the number of these which were acute, minor, or regarding a chronic condition. RESULTS: We assessed 62 consultations (41 general practitioner and 21 physician associates) from five general practitioners and four physician associates. All consultations were assessed as safe; but general practitioners were rated higher than PAs in all elements of consultation. The general practitioners were more likely than physician associates to see people with multiple presenting complaints (p<0.0001) and with chronic disease related complaints (p = 0.008). Assessors correctly identified general practitioner consultations but not physician associates. The Leicester Assessment Package had limited inter-rater and intra-rater reliability. CONCLUSIONS: The physician associate consultations were with a less complex patient group. They were judged as competent and safe, although general practitioner consultations, unsurprisingly, were rated as more competent. Physician associates offer a complementary addition to the medical workforce in general practice. PMID- 27560180 TI - Correction: Polymorphic Alu Insertion/Deletion in Different Caste and Tribal Populations from South India. AB - [This corrects the article DOI: 10.1371/journal.pone.0157468.]. PMID- 27560181 TI - Finding the Primary Care Providers in the Specialist-Dominant Primary Care Setting of Korea: A Cluster Analysis. AB - OBJECTIVE: This study aimed to identify private clinics that have a potential to perform the role of primary care providers (PCPs) in a primary care setting in Korea where private specialists are dominant. METHODS: The 2013 National Patient Sample claim data of Health Insurance Review and Assessment Service in Korea was used. Two-step cluster analysis was performed using characteristics of private clinics, and patient and utilization characteristics of 27,797 private clinics. External validation of clusters was performed by assessing the association among clusters and outcomes of care provided by private clinics. Stability of clusters was cross-validated using discriminant analysis. RESULTS: The result classified more than a half of private clinics into a potential PCP cluster. These were private clinics with specialties considered to be those of primary care physicians and were more likely to be located in non-metropolitan areas than specialized PCPs were. Compared to specialized PCPs, they had a higher percentage of pediatric and geriatric patients, patients with greater disease severity, a higher percentage of patients with complex comorbidities or with simple or minor disease groups, a higher number of patients and visits, and the same or higher quality of primary care. The most important factor in explaining variations between PCP clusters was the number of simple or minor disease groups per patient. CONCLUSION: This study identified potential PCPs and suggested the identifying criteria for PCPs. It will provide useful information for formulation of a primary care strengthening policy to policy makers in Korea as well as other countries with similar specialist-dominant primary care settings. PMID- 27560182 TI - High and Low Salt Intake during Pregnancy: Impact on Cardiac and Renal Structure in Newborns. AB - INTRODUCTION: Previous studies from our laboratory demonstrated that dietary salt overload and salt restriction during pregnancy were associated with cardiac and renal structural and/or functional alterations in adult offspring. The present study evaluated renal and cardiac structure and the local renin-angiotensin system in newborns from dams fed high-, normal- or low-salt diets during pregnancy. METHODS: Female Wistar rats were fed low- (LS, 0.15% NaCl), normal- (NS, 1.3% NaCl) or high- (HS, 8% NaCl) salt diets during pregnancy. Kidneys and hearts were collected from newborns (n = 6-8/group) during the first 24 hours after birth to evaluate possible changes in structure using stereology. Protein expression of renin-angiotensin system components was evaluated using an indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: No differences between groups were observed in total renal volume, volume of renal compartments or number of glomeruli. The transverse diameter of the nuclei of cardiomyocytes was greater in HS than NS males in the left and right ventricles. Protein expression of the AT1 receptor was lower in the kidneys of the LS than in those of the NS and HS males but not females. Protein expression of the AT2 receptor was lower in the kidneys of the LS males and females than in those of the NS males and females. CONCLUSION: High salt intake during pregnancy induced left and right ventricular hypertrophy in male newborns. Salt restriction during pregnancy reduced the expression of renal angiotensin II receptors in newborns. PMID- 27560184 TI - Sequential Treatment of Delayed Endovascular Coil Extrusion From a Carotid Artery Pseudoaneurysm After Tonsillectomy. PMID- 27560183 TI - Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to Guide Reductionist Vaccine Design. AB - An optimal HIV vaccine should induce broadly neutralizing antibodies (bnAbs) that neutralize diverse viral strains and subtypes. However, potent bnAbs develop in only a small fraction of HIV-infected individuals, all contain rare features such as extensive mutation, insertions, deletions, and/or long complementarity determining regions, and some are polyreactive, casting doubt on whether bnAbs to HIV can be reliably induced by vaccination. We engineered two potent VRC01-class bnAbs that minimized rare features. According to a quantitative features frequency analysis, the set of features for one of these minimally mutated bnAbs compared favorably with all 68 HIV bnAbs analyzed and was similar to antibodies elicited by common vaccines. This same minimally mutated bnAb lacked polyreactivity in four different assays. We then divided the minimal mutations into spatial clusters and dissected the epitope components interacting with those clusters, by mutational and crystallographic analyses coupled with neutralization assays. Finally, by synthesizing available data, we developed a working-concept boosting strategy to select the mutation clusters in a logical order following a germline-targeting prime. We have thus developed potent HIV bnAbs that may be more tractable vaccine goals compared to existing bnAbs, and we have proposed a strategy to elicit them. This reductionist approach to vaccine design, guided by antibody and antigen structure, could be applied to design candidate vaccines for other HIV bnAbs or protective Abs against other pathogens. PMID- 27560186 TI - Correction: To Check or Not to Check? A Qualitative Study on How the Public Decides on Health Checks for Cardiovascular Disease Prevention. AB - [This corrects the article DOI: 10.1371/journal.pone.0159438.]. PMID- 27560185 TI - Evidence of Online Performance Deterioration in User Sessions on Reddit. AB - This article presents evidence of performance deterioration in online user sessions quantified by studying a massive dataset containing over 55 million comments posted on Reddit in April 2015. After segmenting the sessions (i.e., periods of activity without a prolonged break) depending on their intensity (i.e., how many posts users produced during sessions), we observe a general decrease in the quality of comments produced by users over the course of sessions. We propose mixed-effects models that capture the impact of session intensity on comments, including their length, quality, and the responses they generate from the community. Our findings suggest performance deterioration: Sessions of increasing intensity are associated with the production of shorter, progressively less complex comments, which receive declining quality scores (as rated by other users), and are less and less engaging (i.e., they attract fewer responses). Our contribution evokes a connection between cognitive and attention dynamics and the usage of online social peer production platforms, specifically the effects of deterioration of user performance. PMID- 27560187 TI - Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors. AB - Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs) are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i) combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii) sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii) strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the clinic. PMID- 27560188 TI - eduSPIM: Light Sheet Microscopy in the Museum. AB - LIGHT SHEET MICROSCOPY IN THE MUSEUM: Light sheet microscopy (or selective plane illumination microscopy) is an important imaging technique in the life sciences. At the same time, this technique is also ideally suited for community outreach projects, because it produces visually appealing, highly dynamic images of living organisms and its working principle can be understood with basic optics knowledge. Still, the underlying concepts are widely unknown to the non scientific public. On the occasion of the UNESCO International Year of Light, a technical museum in Dresden, Germany, launched a special, interactive exhibition. We built a fully functional, educational selective plane illumination microscope (eduSPIM) to demonstrate how developments in microscopy promote discoveries in biology. DESIGN PRINCIPLES OF AN EDUCATIONAL LIGHT SHEET MICROSCOPE: To maximize educational impact, we radically reduced a standard light sheet microscope to its essential components without compromising functionality and incorporated stringent safety concepts beyond those needed in the lab. Our eduSPIM system features one illumination and one detection path and a sealed sample chamber. We image fixed zebrafish embryos with fluorescent vasculature, because the structure is meaningful to laymen and visualises the optical principles of light sheet microscopy. Via a simplified interface, visitors acquire fluorescence and transmission data simultaneously. THE EDUSPIM DESIGN IS TAILORED EASILY TO FIT NUMEROUS APPLICATIONS: The universal concepts presented here may also apply to other scientific approaches that are communicated to laymen in interactive settings. The specific eduSPIM design is adapted easily for various outreach and teaching activities. eduSPIM may even prove useful for labs needing a simple SPIM. A detailed parts list and schematics to rebuild eduSPIM are provided. PMID- 27560189 TI - Arbuscular mycorrhizal fungi communities from tropical Africa reveal strong ecological structure. AB - Understanding the distribution and diversity of arbuscular mycorrhizal fungi (AMF) and the rules that govern AMF assemblages has been hampered by a lack of data from natural ecosystems. In addition, the current knowledge on AMF diversity is biased towards temperate ecosystems, whereas little is known about other habitats such as dry tropical ecosystems. We explored the diversity and structure of AMF communities in grasslands, savannas, dry forests and miombo in a protected area under dry tropical climate (Gorongosa National Park, Mozambique) using 454 pyrosequencing. In total, 147 AMF virtual taxa (VT) were detected, including 22 VT new to science. We found a high turnover of AMF with ? 12% of VT present in all vegetation types. Forested areas supported more diverse AMF communities than savannas and grassland. Miombo woodlands had the highest AMF richness, number of novel VT, and number of exclusive and indicator taxa. Our data reveal a sharp differentiation of AMF communities between forested areas and periodically flooded savannas and grasslands. This marked ecological structure of AMF communities provides the first comprehensive landscape-scale evidence that, at the background of globally low endemism of AMF, local communities are shaped by regional processes including environmental filtering by edaphic properties and natural disturbance. PMID- 27560190 TI - Physiological Responses of Two Epiphytic Bryophytes to Nitrogen, Phosphorus and Sulfur Addition in a Subtropical Montane Cloud Forest. AB - Atmospheric depositions pose significant threats to biodiversity and ecosystem function. However, the underlying physiological mechanisms are not well understood, and few studies have considered the combined effects and interactions of multiple pollutants. This in situ study explored the physiological responses of two epiphytic bryophytes to combined addition of nitrogen, phosphorus and sulfur. We investigated the electrical conductivity (EC), total chlorophyll concentration (Chl), nutrient stoichiometry and chlorophyll fluorescence signals in a subtropical montane cloud forest in south-west China. The results showed that enhanced fertilizer additions imposed detrimental effects on bryophytes, and the combined enrichment of simulated fertilization exerted limited synergistic effects in their natural environments. On the whole, EC, Chl, the effective quantum yield of photosystem II (PhiPSII) and photochemical quenching (qP) were the more reliable indicators of increased artificial fertilization. However, conclusions on nutrient stoichiometry should be drawn cautiously concerning the saturation uptake and nutrient interactions in bryophytes. Finally, we discuss the limitations of prevailing fertilization experiments and emphasize the importance of long-term data available for future investigations. PMID- 27560191 TI - Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect. AB - BACKGROUND: Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. OBJECTIVES: To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. METHODS: We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. RESULTS: None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. CONCLUSION: This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional comparators outside of those of primary interest to allow for the exploration of heterogeneity. PMID- 27560193 TI - Long-Term Outcomes in the Treatment of Classical Trigeminal Neuralgia by Gamma Knife Radiosurgery: A Retrospective Study in Patients With Minimum 2-Year Follow up. AB - BACKGROUND: Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN). OBJECTIVE: To retrospectively analyze long-term outcomes for TN using GKRS achieved at our institution. METHODS: One hundred seventeen patients with medically refractory TN treated by GKRS at our institution were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range: 80-90 Gy; median: 90 Gy). Clinical response was defined based on the Burchiel classification. We considered classes I and II as a complete response. For toxicity, we use the Barrow Neurological Institute facial numbness scale. Mean duration of follow-up was 66 months (range: 24-171 months). RESULTS: Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]: 78%-94%), 81% at 5 years (CI: 72%-91%), and 76% at 7 years (CI: 65%-90%). Complete response rates (classes I II) were 91% at 3 years (CI: 86%-97%), 86% at 5 years (CI: 79%-93%), and 82% at 7 years (CI: 72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%. CONCLUSION: GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. We consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients. ABBREVIATIONS: CI, confidence intervalGKRS, gamma knife radiosurgeryMVD, microvascular decompressionRS, radiosurgeryTN, trigeminal neuralgia. PMID- 27560194 TI - Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room. AB - The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species. PMID- 27560195 TI - Resveratrol improves TNF-alpha-induced endothelial dysfunction in a coculture model of a Caco-2 with an endothelial cell line. AB - The bioactivity of trans-resveratrol (RSV), an important wine polyphenol, and of its metabolites was investigated in a more relevant setup comprising an in vitro coculture cell model that combines intestinal absorption and conjugation with changes in endothelial function, which is primarily affected in cardiovascular diseases. Caco-2 and endothelial EA.hy926 cells were grown in a coculture, and Caco-2 cells were treated with RSV in the coculture and in two different sequential setups for 4 h and 24 h. Transported metabolites were investigated by UPLC-MS/MSE, and the effects on NO production, ROS inhibition and secretion of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-alpha-activated and nonactivated endothelial cells. RSV and four conjugated metabolites, two sulfates and two glucuronides, were identified after intestinal transport. In both coculture and sequential systems, RSV at 20 MUM strongly induced NO production. Changes in ROS and NO levels demonstrated a clear effect of crosstalk between cells in the coculture. The secretion of proinflammatory cytokines and VEGF was largely increased by treatment with TNF-alpha (inflammatory condition). The polyphenol intervention significantly reduced the levels of VEGF, ROS, IL-8 and ICAM-1, with a more pronounced effect in TNF-alpha-activated endothelial cells. In conclusion, RSV and its metabolites showed accentuated bioactivity on TNF alpha-induced inflammation, and the metabolism of endothelial cells as a biological target was not only influenced by these phenolics but also by the communication between distinct cell lines, showing a new perspective for investigations on polyphenol intervention and its biological outcomes. PMID- 27560198 TI - [Intraocular Lenses with Special Properties]. PMID- 27560196 TI - Treatment of Systemic Sclerosis-related Interstitial Lung Disease: A Review of Existing and Emerging Therapies. AB - Although interstitial lung disease accounts for the majority of deaths of patients with systemic sclerosis, treatment options for this manifestation of the disease are limited. Few high-quality, randomized, controlled trials exist for systemic sclerosis-related interstitial lung disease, and historically, studies have favored the use of cyclophosphamide. However, the benefit of cyclophosphamide for this disease is tempered by its complex adverse event profile. More recent studies have demonstrated the effectiveness of mycophenolate for systemic sclerosis-related interstitial lung disease, including Scleroderma Lung Study II. This review highlights the findings of this study, which was the first randomized controlled trial to compare cyclophosphamide with mycophenolate for the treatment of systemic sclerosis-related interstitial lung disease. The results reported in this trial suggest that there is no difference in treatment efficacy between mycophenolate and cyclophosphamide; however, mycophenolate appears to be safer and more tolerable than cyclophosphamide. In light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation. This review further explores how reaching a consensus on appropriate study end points, as well as trial enrichment criteria, is central to improving our ability to judiciously evaluate the safety and efficacy of emerging experimental therapies for systemic sclerosis related interstitial lung disease. PMID- 27560192 TI - Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases. AB - Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors. PMID- 27560199 TI - [Special Intraocular Lenses in Refractive Lens Surgery]. AB - PURPOSE: Many different models and types of special intraocular lenses (IOL) are now available for refractive lens surgery. In particular, toric and multifocal IOL need specific conditions to achieve satisfactory results. For multifocal IOL, many models with different optical principles are available. For optimal individual patient-centred care, it is necessary to consider several different options. With special refractive lenses, the principle objective for the patients is to become less dependent on glasses. MATERIAL AND METHODS: Different IOL are evaluated on the basis of published studies and our own experience and data. RESULTS: IOL filtering blue light should not be classified as special IOL, but should be used as standards. Aspherical IOL are only beneficial in special situations. Toric IOL give reliable and good results, as long as certain specific requirements are considered. Multifocal IOL are still an optical compromise, although they are the only IOL that can reliably make the patient independent of glasses. To achieve satisfying results, the optimal IOL model should be selected individually. CONCLUSION: Many refractive needs can now be adequately satisfied by special IOL. The surgeon should provide ideal perioperative conditions, and he should be aware of the different IOL principles if he is to give the patient optimal advice. This can help to avoid upsetting both patients and ophthalmologists. PMID- 27560197 TI - Novel GM-CSF-based vaccines: One small step in GM-CSF gene optimization, one giant leap for human vaccines. AB - Granulocyte macrophage-colony stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that is known to facilitate vaccine efficacy by promoting the development and prolongation of both humoral and cellular immunity. In the past years we have generated a novel codon-optimized GM-CSF gene as an adjuvant. The codon-optimized GM-CSF gene significantly increased protein expression levels in all cells tested and helped in generating a strong immune responses against HIV-1 Gag and HPV-associated cancer. Here, we review the literature dealing with the adjuvant activity of GM-CSF both in animal models and clinical trials. We anticipate that the codon-optimized GM-CSF gene offers a practical molecular strategy for potentiating immune responses to tumor cell based vaccinations as well as other immunotherapeutic strategies. PMID- 27560200 TI - [Duration of Examination and Patient Comfort with a New Biometric Device, in Comparison to Three Established Devices]. AB - PURPOSE: The aim of this study was to evaluate the duration of the preoperative examination and patient comfort in measurements with an Image Guided System (Verion, Alcon), which is used for the calculation and intraoperative alignment of toric intraocular lenses, in comparison to established keratometry devices. PATIENTS AND METHODS: In a prospective, monocentric, open, ethics committee controlled study, 150 eyes of 150 ophthalmologically healthy volunteers were examined by a single examiner. Three measurements were performed with the Verion Image Guided System and - for comparison - one measurement each with IOLMaster 500, Lenstar LS900 and Pentacam HR. The measurement time was recorded with a stopwatch. For the analysis, patients were divided into three age groups (young, middle, old). Patient comfort was assessed using a questionnaire, which focussed on grading the whole measurement, as well as brightness of light, head posture and subjective duration. RESULTS: The mean age of the volunteers was 40.5 years (18-78 years). The mean duration of measurement was as follows: first Verion measurement 54.0 +/- 42.7 seconds (n = 149), second Verion measurement 42.0 +/- 20.5 s (n = 144), third Verion measurement 44.7 +/- 25.2 s (n = 143), IOLMaster 500 46.3 +/- 22.4 s (n = 147), Lenstar LS900 46.6 +/- 14.4 s (n = 146) and Pentacam HR 46.6 +/- 25.5 s (n = 147). Only the first and second Verion measurements were statistically different (p < 0.01). There were no statistical differences between the age groups, with the single exception of young versus old with the Pentacam (p < 0.01). Subjective patient comfort (n = 143) was very high for all devices and rated as "not uncomfortable" or "slightly uncomfortable". CONCLUSION: The duration of the preoperative examination with the Verion Image Guided System is comparable to established keratometry devices. However, IOL calculation with the Verion requires measurement of axial length and anterior chamber depth with another biometric device, which requires additional time. No age dependent differences were found. The examination can be easily integrated into clinical routine and is well tolerated by patients. PMID- 27560201 TI - Notes from the Field: Cluster of Tuberculosis Cases Among Marshallese Persons Residing in Arkansas - 2014-2015. AB - During early September 2014, the Arkansas Department of Health identified an increased number of tuberculosis (TB) cases among a unique population in a well circumscribed geographical area in northwest Arkansas. The Compact of Free Association Act of 1985 (Public Law 99-239, amended in 2003 by Public Law 108 188) established the Republic of the Marshall Islands (RMI) as an independent nation, and persons from the RMI can travel freely (with valid RMI passport) to and from the United States as nonimmigrants without visas (1). Marshallese started settling in northwest Arkansas during the early 1990s because of employment and educational opportunities (2). According to the 2010 Census, an estimated 4,300 Marshallese resided in Arkansas (2), mostly within one county which ranked 6th in the United States for counties with the highest percentage of Native Hawaiians and Other Pacific Islanders (3). It is estimated that this number has been growing steadily each year since the 2010 Census; however, obtaining an accurate count is difficult. The RMI is a TB high-incidence country, with a case-rate of 212.7 per 100,000 persons for 2014, whereas the case-rate was 3.1 per 100,000 persons in Arkansas and 2.9 per 100,000 persons in the United States (4,5). Screening for either active TB or latent TB infection (LTBI) is not required for Marshallese entry to the United States (1). PMID- 27560202 TI - Capecitabine and the Risk of Fingerprint Loss. PMID- 27560203 TI - Structural Diversity of Ligand-Binding Androgen Receptors Revealed by Microsecond Long Molecular Dynamics Simulations and Enhanced Sampling. AB - Androgen receptor (AR) plays important roles in the development of prostate cancer (PCa). The antagonistic drugs, which suppress the activity of AR, are widely used in the treatment of PCa. However, the molecular mechanism of antagonism about how ligands affect the structures of AR remains elusive. To better understand the conformational variability of ARs bound with agonists or antagonists, we performed long time unbiased molecular dynamics (MD) simulations and enhanced sampling simulations for the ligand binding domain of AR (AR-LBD) in complex with various ligands. Based on the simulation results, we proposed an allosteric pathway linking ligands and helix 12 (H12) of AR-LBD, which involves the interactions among the ligands and the residues W741, H874, and I899. The interaction pathway provides an atomistic explanation of how ligands affect the structure of AR-LBD. A repositioning of H12 was observed, but it is facilitated by the C-terminal of H12, instead of by the loop between helix 11 (H11) and H12. The bias-exchange metadynamics simulations further demonstrated the above observations. More importantly, the free energy profiles constructed by the enhanced sampling simulations revealed the transition process between the antagonistic form and agonistic form of AR-LBD. Our results would be helpful for the design of more efficient antagonists of AR to combat PCa. PMID- 27560204 TI - Asymmetric Cyclization of N-Sulfonyl Alkenyl Amides Catalyzed by Iridium/Chiral Diene Complexes. AB - Iridium/chiral diene complexes efficiently catalyzed the asymmetric cyclization of N-sulfonyl alkenyl amides to give the corresponding 2-pyrrolidone derivatives with high enantioselectivity. A mechanistic study revealed that the reaction proceeds via nucleophilic attack of the amide on the alkene moiety. PMID- 27560254 TI - Malignant pleural fluid from mesothelioma has potent biological activities. AB - BACKGROUND AND OBJECTIVE: Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma. METHODS: Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed. RESULTS: Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan-blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23-fold over controls (all P < 0.0001). The fluid also induced cell migration by (median) 2.13-fold in six mesothelioma cell lines using scratch-wound assay. In a murine flank model of mesothelioma, tumour infused with daily instillations of pleural fluid grew significantly faster over saline controls (median 52.5 cm2 vs 28.0 cm2 at day 13, P = 0.028). Addition of MPE (diluted to 30%) to culture media significantly protected mesothelioma from cisplatin/pemetrexed-induced cell death in all three cell lines tested (median fold reduction of 1.29, 1.98 and 3.90, all P < 0.001 vs control). The growth effects of matched pleural fluid and cultured mesothelioma cells from the same patients did not differ significantly from unmatched pairs. CONCLUSION: This 'proof-of-concept' study reveals potent biological capabilities of malignant pleural fluid in mesothelioma pathobiology. PMID- 27560255 TI - Evaluation of the dose metric for acute lung inflammogenicity of fast-dissolving metal oxide nanoparticles. AB - Although surface area metric was suggested as an appropriate dose metric for acute lung inflammation of NPs, it might not be effective for fast-dissolving NPs because they lose their reactive surface when dissolved in the phagolysosomes. Herein, we evaluated the dose metric for fast-dissolving NPs using a rat intratracheal instillation model. A panel of fast-dissolving NPs (CoO, CuO and ZnO) and their constituent metal ions (CoCl2, CuCl2 and ZnCl2) were compiled and each compound was intratracheally instilled into the lungs of female Wistar rats at the same molar concentrations in the NP doses (40, 100 and 400 MUg/rat). The toxicity endpoints including cytological and biochemical data in bronchoalveolar lavage fluid were evaluated at 24 h after instillation. To evaluate the dose metric, each toxicity endpoint was plotted against the instilled dose (mass or surface area) or the equivalent dose (mass or surface area) that was weighted by the ratio of specific dose-generated responses between metal chlorides. Dose response curves of fast-dissolving NPs about percentage of granulocytes, lactate dehydrogenase levels and total protein levels showed similar pattern but slightly less potential than those of their respective metal chlorides. When each toxicity endpoint was plotted against the equivalent mass dose, three types of NPs showed more overlapping dose-response curves than other dose metrics. In conclusion, this study implies that the equivalent mass dose is an appropriate dose metric for fast-dissolving NPs and the main factor determining the slope of the dose response curve is the intrinsic toxicity of the their constituent ions. PMID- 27560256 TI - The effect of behavioral intervention and nutrition education program on serum lipid profile, body weight and blood pressure in Iranian individuals with spinal cord injury: A randomized clinical trial. AB - OBJECTIVE: The efficacy of nutrition education on body weight and serum lipids has not yet been described in patients with spinal cord injury (SCI). In the present study, we examined the effect of a 7-month nutrition education program on lipid profile and body weight in individuals with SCI. DESIGN: Randomized clinical trial. SETTING: A tertiary rehabilitation center. PARTICIPANTS: Patients with SCI who were referred to Brain and Spinal Cord Injury Research Center. INTERVENTION: The nutrition education program consisted of 5 education sessions during a period of 7 months. OUTCOME MEASURES: Body weight and serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measure at the beginning of the trial and after 7 months. Two-way repeated measure analysis of variance (ANOVA) was used. RESULTS: Total of 57 patients (27 in control group and 30 in education group) participated. Nutrition education program showed no significant effect on the levels of TC, TG, LDL-C and HDL-C (P: 0.224, 0.172, 0.107 and 0.081, respectively). No significant changes in weight and waist circumflex have been observed as well (P: 0.970 and 0.361, respectively). CONCLUSION: Our findings do not support a significant influence of nutrition education program on weight and lipid profile. It seems that the nutrition education program alone is not adequately effective to have beneficial influence on weight and lipid profile. Clinical trial registration No.: IRCT201406215968N3. PMID- 27560257 TI - Atrial fibrillation and stroke: unrecognised and undertreated. PMID- 27560258 TI - Canada's inquiry into violence toward Indigenous women. PMID- 27560259 TI - Health-care crisis in Turkey: urgent actions needed. PMID- 27560260 TI - Digital medicine: empowering both patients and clinicians. PMID- 27560261 TI - Learning from every stillbirth and neonatal death. PMID- 27560262 TI - UN political declaration on HIV and AIDS: where to begin? PMID- 27560263 TI - Peru's new health minister outlines priorities. PMID- 27560264 TI - Child poverty continues to rise in the UK. PMID- 27560265 TI - Frontline: Providing health care in Greece's refugee camps. PMID- 27560266 TI - Off the cuff: rebooting blood pressure treatment. PMID- 27560267 TI - Shengshou Hu: leader of cardiac surgery and health reform in China. PMID- 27560268 TI - Rebuilding patient-physician trust in China. PMID- 27560269 TI - Expectations of students of traditional Chinese medicine. PMID- 27560270 TI - Bigotry, bills, and medicine: lessons from the USA. PMID- 27560271 TI - Telemedicine expedites access to optimal acute stroke care. PMID- 27560272 TI - Institutional corruption, health-sector reforms, and health status in Nigeria. PMID- 27560273 TI - Weighing up dietary patterns. PMID- 27560274 TI - Weighing up dietary patterns. PMID- 27560275 TI - Weighing up dietary patterns - Authors' reply. PMID- 27560276 TI - Stroke prevention in atrial fibrillation. AB - Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating. Most could be prevented if efforts were directed towards detection of atrial fibrillation before stroke occurs, through screening or case finding, and treatment of all patients with atrial fibrillation at increased risk of stroke with well controlled vitamin K antagonists or non-vitamin K antagonist anticoagulants. The default strategy should be to offer anticoagulant thromboprophylaxis to all patients with atrial fibrillation unless defined as truly low risk by simple validated risk scores, such as CHA2DS2-VASc. Assessment of bleeding risk using the HAS-BLED score should focus attention on reversible bleeding risk factors. Finally, patients need support from physicians and various other sources to start anticoagulant treatment and to ensure adherence to and persistence with treatment in the long term. PMID- 27560277 TI - Rate control in atrial fibrillation. AB - Control of the heart rate (rate control) is central to atrial fibrillation management, even for patients who ultimately require control of the rhythm. We review heart rate control in patients with atrial fibrillation, including the rationale for the intervention, patient selection, and the treatments available. The choice of rate control depends on the symptoms and clinical characteristics of the patient, but for all patients with atrial fibrillation, rate control is part of the management. Choice of drugs is patient-dependent. beta blockers, alone or in combination with digoxin, or non-dihydropyridine calcium-channel blockers (not in heart failure) effectively lower the heart rate. Digoxin is least effective, but a reasonable choice for physically inactive patients aged 80 years or older, in whom other treatments are ineffective or are contraindicated, and as an additional drug to other rate-controlling drugs, especially in heart failure when instituted cautiously. Atrioventricular node ablation with pacemaker insertion for rate control should be used as an approach of last resort but is also an option early in the management of patients with atrial fibrillation treated with cardiac resynchronisation therapy. However, catheter ablation of atrial fibrillation should be considered before atrioventricular node ablation. Although rate control is a top priority and one of the first management issues for all patients with atrial fibrillation, many issues remain. PMID- 27560278 TI - Rhythm control in atrial fibrillation. AB - Many patients with atrial fibrillation have substantial symptoms despite ventricular rate control and require restoration of sinus rhythm to improve their quality of life. Acute restoration (ie, cardioversion) and maintenance of sinus rhythm in patients with atrial fibrillation are referred to as rhythm control. The decision to pursue rhythm control is based on symptoms, the type of atrial fibrillation (paroxysmal, persistent, or long-standing persistent), patient comorbidities, general health status, and anticoagulation status. Many patients have recurrent atrial fibrillation and require further intervention to maintain long term sinus rhythm. Antiarrhythmic drug therapy is generally recommended as a first-line therapy and drug selection is on the basis of the presence or absence of structural heart disease or heart failure, electrocardiographical variables, renal function, and other comorbidities. In patients who continue to have recurrent atrial fibrillation despite medical therapy, catheter ablation has been shown to substantially reduce recurrent atrial fibrillation, decrease symptoms, and improve quality of life, although recurrence is common despite continued advancement in ablation techniques. PMID- 27560279 TI - Time to get happy: associations of time perspective with indicators of well being. AB - The present study examined associations of time perspective (TP) with indicators of well-being including satisfaction with life, anxiety and depression, after controlling for sociodemographic factors. Adult participants (N = 413) completed a web-based questionnaire that included a short version of the Zimbardo Time Perspective Inventory, the State-Trait Anxiety Inventory, and the Center for Epidemiologic Studies-Depression Scale. Life satisfaction was more strongly associated with the present hedonistic dimension, suggesting that the tendency to take risks and to fulfil one's desires may lead to experiencing pleasure in a 'seize the day' approach to life. The existence of depressive symptoms and elevated anxiety levels were associated with higher scores on the past present and the present fatalistic dimensions, suggesting that feeling hopeless, or dwelling on bad moments from the past may be largely related to feeling depressed and anxious. Considering the recently reported implications of TP in clinical and counseling settings, the present study contributes to the growing body of research that associates TP with mental health and psychological well-being. PMID- 27560280 TI - Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor. AB - Herein we report the design, synthesis, bioinformatic and biological studies of benzimidazole and benzothiophene derivatives as new cannabinoid receptor ligands. To test the hypothesis that the lack of a hydrogen bond interaction between benzimidazole and benzothiophene derivatives with Lys192 reduces their affinity for CB1 receptors (as we previously reported) and leads to CB2 selectivity, most of the tested compounds do not exhibit hydrogen bond acceptors. All compounds displayed mostly CB2 selectivity, although this was more pronounced in the benzimidazoles derivatives. Furthermore, docking assays revealed a ?-cation interaction with Lys109 which could play a key role for the CB2 selectivity index. The series displayed low toxicity on five different cell lines. Derivative 8f presented the best binding profile (Ki = 0.08 MUM), high selectivity index (KiCB1/KiCB2) and a low citoxicity. Interestingly, in cell viability experiments, using HL-60 cells (expressing exclusively CB2 receptors), all synthesised compounds were shown to be cytotoxic, suggesting that a CB2 agonist response may be involved. PMID- 27560281 TI - Substituted 4-morpholine N-arylsulfonamides as gamma-secretase inhibitors. AB - The design, synthesis, SAR, and biological profile of a substituted 4-morpholine sulfonamide series of gamma-secretase inhibitors (GSIs) were described. In several cases, the resulting series of GSIs reduced CYP liabilities and improved gamma-secretase inhibition activity compared to our previous research series. Selected compounds demonstrated significant reduction of amyloid-beta (Abeta) after acute oral dosing in a transgenic animal model of Alzheimer's disease (AD). PMID- 27560282 TI - Evaluation of selected 3D virtual screening tools for the prospective identification of peroxisome proliferator-activated receptor (PPAR) gamma partial agonists. AB - The peroxisome proliferator-activated receptor (PPAR) gamma regulates the expression of genes involved in adipogenesis, lipid homeostasis, and glucose metabolism, making it a valuable drug target. However, full activation of the nuclear receptor is associated with unwanted side effects. Research therefore focuses on the discovery of novel partial agonists, which show a distinct protein ligand interaction pattern compared to full agonists. Within this study, we employed pharmacophore- and shape-based virtual screening and docking independently and in parallel for the identification of novel PPARgamma ligands. The ten top-ranked hits retrieved with every method were further investigated with external in silico bioactivity profiling tools. Subsequent biological testing not only confirmed the binding of nine out of the 29 selected test compounds, but enabled the direct comparison of the method performances in a prospective manner. Although all three methods successfully identified novel ligands, they varied in the numbers of active compounds ranked among the top-ten in the virtual hit list. In addition, these compounds were in most cases exclusively predicted as active by the method which initially identified them. This suggests, that the applied programs and methods are highly complementary and cover a distinct chemical space of PPARgamma ligands. Further analyses revealed that eight out of the nine active molecules represent novel chemical scaffolds for PPARgamma, which can serve as promising starting points for further chemical optimization. In addition, two novel compounds, identified with docking, proved to be partial agonists in the experimental testing. PMID- 27560283 TI - Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation. AB - As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT6 receptor (Kb = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC50hAChE = 12 nM, IC50hBuChE = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD. PMID- 27560285 TI - Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti diabetic agents. AB - A series of xanthine derivatives as potent dual ligands targeting DPP-IV and GPR119 was discovered through an approach of the merged pharmacophores of GPR119 agonists and DPP-IV inhibitor linagliptin. Systematic optimization of general structure 5 led to the identification of compound 20i with selective DPP-IV inhibition, good GPR119 agonism activity and favorable metabolic stability. Docking study was performed to elucidate the potent DPP-IV inhibition of 20i. Compound 20i may serve as a tool compound for further design of anti-diabetic drugs targeting both DPP-IV and GPR119. PMID- 27560286 TI - Insights into the structural integrity and dynamics of siRNA-PAZ complex. PMID- 27560284 TI - New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4 methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment. AB - Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer's Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacological and behavioral studies on our hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new molecule series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Molecular modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 8a showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate molecular target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclinical development. PMID- 27560287 TI - From Barley Straw to Valuable Polyols: A Sustainable Process Using Ethanol/Water Mixtures and Hydrogenolysis over Ruthenium-Tungsten Catalyst. AB - Organosolv fractionation of barley straw followed by a hydrogenolysis reaction of the resulting organosolv pulp over a heterogeneous catalyst containing ruthenium and tungsten on activated carbon (Ru-W/AC) is a potential pathway to produce valuable chemicals from lignocellulose-based feedstock in a future biorefinery. Polyols, such as ethylene glycol, propylene glycol, or 1,2-butanediol, can be obtained with a very high yield of 70 % using organosolv barley pulp pretreated in a 50:50 wt % ethanol/water solution at 200 degrees C and a processing time of one hour. Moreover, we investigated the influence of several pretreatment parameters (e.g., solvent/water ratio, reaction temperature, and reaction time) on the pulp composition and product distribution obtained during the hydrogenolysis reaction to reduce the production of undesired side molecules. Finally, the optimal organosolv pretreatment conditions for straw were successfully transferred to other lignocellulose-based feedstock, namely bamboo foliage and hemp shives. PMID- 27560288 TI - Median arcuate ligament syndrome: Predictor of ischemic complications? AB - Median arcuate ligament syndrome (MALS) is a pathologic entity that can affect the celiac axis. Due to the extensive collateral network of mesenteric circulation, stenosis of one mesenteric artery does not lead to significant symptoms. The purpose of this study was to describe multidetector computed tomography (MDCT) angiography findings of celiac artery entrapment by the median arcuate ligament and determine those patients with high risks of ischemic complications. From January 2012 to March 2016, 103 patients with celiac artery (CA) compression by median arcuate ligament were detected. In 23 patients collateral circulation was developed. In order to investigate the problem, we managed to estimate the correlation between range of stenosis of CA and presence of collateral circulation between the celiac artery (CA) and superior mesenteric artery (SMA). A statistically significant correlation was found between range of CA stenosis and collateral circulation presence (Spearman's correlation coefficient 0.339, P < 0.0001). In conclusions, based on our observations, we hypothesize that ischemia as a result of mesenteric vessel narrowing by the median arcuate ligament may occur more often than indicated by clinical symptoms and described in literature. Clin. Anat. 29:1025-1030, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27560290 TI - Commentary on a Randomized Clinical Trial of Comparing Monophasic Monodensified and Biphasic Nonanimal Stabilized Hyaluronic Acid Dermal Fillers in Treatment of Asian Nasolabial Folds. PMID- 27560289 TI - A Randomized Clinical Trial of Comparing Monophasic Monodensified and Biphasic Nonanimal Stabilized Hyaluronic Acid Dermal Fillers in Treatment of Asian Nasolabial Folds. AB - BACKGROUND: Cross-linked hyaluronic acids (HAs) with varying characteristics and formulations are available. Despite the popularity of HA, limited studies compared the effectiveness of monophasic monodensified hyaluronic acid (MMHA) and biphasic nonanimal stabilized hyaluronic acid (BHA) products in correcting nasolabial folds (NLFs) in the Asian population. OBJECTIVE: This double-blinded, randomized research aimed at evaluating the outcomes of MMHA and BHA products in treating Asian NLFs. MATERIALS AND METHODS: Subjects aged between 18 and 65 years with moderate-to-severe NLFs were randomized to receive MMHA or BHA treatment. A touch-up treatment with the same product was performed at the 4-week follow-up, if needed. The effectiveness was evaluated for 24 weeks by masked investigators. All adverse events were recorded for safety evaluation. RESULTS: Twenty-five subjects in the MMHA Group and twenty-four subjects in the BHA Group finished 24 week follow-up. Results showed that subjects from both groups obtained satisfactory outcome in NLF correction. A lower amount of MMHA was required to achieve a similar result as that of BHA (p < .01). Both HA products maintained the effectiveness at the end of the 24-week follow-up. CONCLUSION: Both MMHA and BHA are effective for correcting NLF in Asian patients, producing satisfactory results. Monophasic monodensified hyaluronic acid provides similar satisfaction to BHA while requiring less injection volume. PMID- 27560291 TI - Fractional CO2 Laser Pretreatment to Autologous Hair Transplantation and Phototherapy Improves Perifollicular Repigmentation in Refractory Vitiligo: A Randomized, Prospective, Half-Lesion, Comparative Study. AB - BACKGROUND: Fractional CO2 laser and autologous hair transplantation are independently effective in the treatment of refractory and stable vitiligo. OBJECTIVE: The authors' purpose was to evaluate the therapeutic efficacy of fractional CO2 laser pretreatment compared with autologous hair transplantation and phototherapy alone for refractory and stable vitiligo. METHODS: A total of 20 patients with refractory and stable vitiligo were enrolled from our clinic. Resistant lesions randomly divided into 2 regions as follows: (1) Part A: fractional CO2 laser pretreatment followed by autologous transplantation and phototherapy, and (2) Part B: autologous transplantation and phototherapy alone. Five days after fractional CO2 laser application to Part A, both treatment regions received a transplant of scalp grafts. On Day 11, the entire lesion was exposed to narrow-band UVB phototherapy, twice a week for 12 weeks. The diameter of perifollicular repigmentation was measured monthly with a caliper. RESULTS: Perifollicular repigmentation was detectable surrounding 74% of grafted hair follicles by Month 3. Furthermore, Part A demonstrated a significantly greater diameter of repigmentation with 6.6 +/- 5.8 mm in Part A compared with 4.3 +/- 1.8 mm in Part B (p = <.001). CONCLUSION: In this study, our results demonstrate improved efficacy of autologous hair transplantation and narrow-band UVB with fractional CO2 laser pretreatment in refractory and stable vitiligo. PMID- 27560292 TI - Subdermal Radiofrequency for Skin Tightening of the Posterior Upper Arms. AB - BACKGROUND: Subsurface thermistor-controlled monopolar radiofrequency (SMRF) is an emerging technology designed to offer a minimally invasive option for tightening of lax skin. The versatility of this technique allows it to be applied to virtually any body site. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of SMRF for tightening of posterior upper arm skin laxity. PATIENTS: This is a prospective, open-label clinical trial involving 12 subjects aged 18 to 65 with moderate-to-severe skin laxity in the posterior upper arms. METHODS/MATERIALS: Each subject received treatment to the bilateral arms resulting in a population of n = 24 arms in the analysis group. Treatment consisted of SMRF delivered at Day 0 of the trial. Follow-up evaluation was conducted at Day 7, 30, and 90 post-treatment. The primary end point was the assessment of skin laxity by a nontreating physician utilizing a standardized 5 point Skin Laxity Grading Scale at baseline, Days 30 and 90. Subject self evaluation of firmness, laxity, texture, and satisfaction was also collected. Circumferential and vertical arm measurements were obtained via digital fractional caliper. An adverse event profile was categorized. RESULTS: Significant improvements in skin laxity were observed at both Day 30 and at Day 90 post-treatment as assessed by the nontreating investigator. Subjects also rated significant improvements in the firmness, texture, and laxity of their treated arms. The majority of subjects were "satisfied" to "extremely satisfied" with their results. Adverse events recorded at Day 7 post-treatment included erythema (4%), contour irregularity (4%), and bruising (13%). All adverse events resolved completely by Day 30 post-treatment. CONCLUSION: Thermistor-controlled SMRF is a safe and effective means to treating posterior upper arm skin laxity. PMID- 27560293 TI - Schwannoma: An Unexpected Presentation. PMID- 27560294 TI - Atg8 lipidation is coordinated in a PtdIns3P-dependent manner by the PROPPIN Atg21. AB - In Saccharomyces cerevisiae Atg8 coupled to phosphatidylethanolamine is a key component of autophagosome biogenesis. Atg21 binds via 2 sites at the circumference of its beta-propeller to PtdIns3P at the phagophore assembly site (PAS). It recruits and arranges both Atg8 and Atg16, which is part of the E3-like ligase complex Atg12-Atg5-Atg16. Binding of Atg8 to Atg21 requires the FK-motif within the N-terminal-helical domain of Atg8 and D146 at the top of the Atg21 beta-propeller. Atg16 binds via D101 and E102 within its coiled-coil domain to Atg21. PMID- 27560295 TI - Ionotropic glutamate receptors: Which ones, when, and where in the mammalian neocortex. AB - A multitude of 18 iGluR receptor subunits, many of which are diversified by splicing and RNA editing, localize to >20 excitatory and inhibitory neocortical neuron types defined by physiology, morphology, and transcriptome in addition to various types of glial, endothelial, and blood cells. Here we have compiled the published expression of iGluR subunits in the areas and cell types of developing and adult cortex of rat, mouse, carnivore, bovine, monkey, and human as determined with antibody- and mRNA-based techniques. iGluRs are differentially expressed in the cortical areas and in the species, and all have a unique developmental pattern. Differences are quantitative rather than a mere absence/presence of expression. iGluR are too ubiquitously expressed and of limited use as markers for areas or layers. A focus has been the iGluR profile of cortical interneuron types. For instance, GluK1 and GluN3A are enriched in, but not specific for, interneurons; moreover, the interneurons expressing these subunits belong to different types. Adressing the types is still a major hurdle because type-specific markers are lacking, and the frequently used neuropeptide/CaBP signatures are subject to regulation by age and activity and vary as well between species and areas. RNA-seq reveals almost all subunits in the two morphofunctionally characterized interneuron types of adult cortical layer I, suggesting a fairly broad expression at the RNA level. It remains to be determined whether all proteins are synthesized, to which pre- or postsynaptic subdomains in a given neuron type they localize, and whether all are involved in synaptic transmission. J. Comp. Neurol. 525:976-1033, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27560297 TI - Malnutrition screening in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease and its association with patient outcomes. AB - OBJECTIVES: There is a paucity of information on the prevalence and clinical implications of malnutrition in patients hospitalised for management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study aimed to fill this gap in knowledge. METHODS: We performed a retrospective observational cohort study of 100 hospitalised AECOPD patients. The Malnutrition Screening Tool (MST) was used to identify patients at risk of malnutrition (MST >=2). Patient characteristics, length of stay, readmission rate, 12-month survival and overall survival were collected using a proforma. RESULTS: MST scores were available in 90 patients, of whom 22% of patients had a MST score of >=2. There were no significant differences in COPD severity, treatment received and biochemical parameters between the groups of patients 'at risk of malnutrition' and those 'not at risk of malnutrition'. Length of stay in hospital was longer in patients 'at risk of malnutrition' (median (IQR): 3.5 (2-7.5) vs. 3.0 (1-5), p = 0.048). Overall survival was significantly reduced in patients with 'at risk of malnutrition' compared to those patients 'not at risk of malnutrition' (337 +/- 245 vs. 670 +/- 292, p < 0.001). CONCLUSIONS: Using the MST we found that one-fifths of our hospitalised AECOPD patients are at 'at risk of malnutrition'. Moreover, this cohort of patients had worse outcomes both during and extending beyond hospitalisation compared to patients 'not at risk of malnutrition'. Our study illustrates the need for routine malnutrition screening for hospitalised AECOPD patients because it has implications for potentially reducing morbidity and mortality in COPD. PMID- 27560296 TI - Employing Arynes in Diels-Alder Reactions and Transition-Metal-Free Multicomponent Coupling and Arylation Reactions. AB - Arynes are highly reactive intermediates having several applications in organic synthesis for the construction of various ortho-disubstituted arenes. Traditionally, arynes are generated in solution from haloarenes under strongly basic conditions. However, the scopes of many of the aryne reactions are limited because of the harsh conditions used for their generation. The renaissance of interest in aryne chemistry is mainly due to the mild conditions for their generation by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates. This Account is focused on the Diels-Alder reaction of arynes and their transition-metal-free application in multicomponent couplings as well as arylation reactions. The Diels-Alder reaction of arynes is a powerful tool for constructing benzo-fused carbocycles and heterocycles. In 2012, we developed an efficient, broad-scope, and scalable Diels-Alder reaction of pentafulvenes with arynes affording benzonorbornadiene derivatives. Subsequently, we accomplished the Diels-Alder reaction of arynes with dienes such as 1,2-benzoquinones and tropones. Moreover, we uncovered a transition-metal-free protocol for the synthesis of 9,10-dihydrophenanthrenes by the reaction of arynes with styrenes that proceeds via a Diels-Alder/ene-reaction cascade. In addition, we demonstrated the reaction of arynes with indene/benzofurans, which proceeds via a tandem [4 + 2]/[2 + 2] sequence. Multicomponent coupling (MCC) involving arynes mainly comprises the initial addition of a nucleophile to the aryne followed by interception of the aryl anion intermediate with an electrophile (provided the nucleophilic and electrophilic moieties do not belong to the same molecule). We have disclosed aryne MCCs initiated by N-heterocycles such as (iso)quinoline, pyridine, and aziridines. When (iso)quinoline is used as the nucleophilic trigger and N-substituted isatin as the third component, the reaction affords spirooxazino(iso)quinolines via 1,4-dipolar intermediates. Unexpectedly, using pyridine affords indolin-2-ones, where the reaction proceeds via the pyridylidene intermediate. Additionally, we developed the phosphine-triggered aryne MCCs for the synthesis of functionalized benzooxaphospholes. In another phase of our work, we studied the synthetic utility of CO2 as a one-carbon synthon in aryne MCCs for the synthesis of phthalimides. Engaging arynes as an aryl source is one of the transition-metal-free methods for arylation reactions. We have demonstrated the N arylation of aromatic tertiary amines and O-arylation of aliphatic alcohols using arynes. It is anticipated that the chemistry of arynes will continue to prosper and will lead to surprising developments for the synthesis of various 1,2 disubstituted arenes of molecular complexity and structural diversity. Future challenges in this area include the utility of arynes in enantioselective transformations and the synthesis and reactions of exotic heterocyclic arynes. PMID- 27560298 TI - Reduced Visual Acuity Following Kidney Stone Extraction. PMID- 27560299 TI - Automated High-Throughput Identification and Characterization of Clinically Important Bacteria and Fungi using Rapid Evaporative Ionization Mass Spectrometry. AB - Rapid evaporative ionization mass spectrometry (REIMS) has been shown to quickly and accurately speciate microorganisms based upon their species-specific lipid profile. Previous work by members of this group showed that the use of a hand held bipolar probe allowed REIMS to analyze microbial cultures directly from culture plates without any prior preparation. However, this method of analysis would likely be unsuitable for a high-throughput clinical microbiology laboratory. Here, we report the creation of a customized platform that enables automated, high-throughput REIMS analysis that requires minimal user input and operation and is suitable for use in clinical microbiology laboratories. The ability of this high-throughput platform to speciate clinically important microorganisms was tested through the analysis of 375 different clinical isolates collected from distinct patient samples from 25 microbial species. After optimization of our data analysis approach, we achieved substantially similar results between the two REIMS approaches. For hand-held bipolar probe REIMS, a speciation accuracy of 96.3% was achieved, whereas for high-throughput REIMS, an accuracy of 93.9% was achieved. Thus, high-throughput REIMS offers an alternative mass spectrometry based method for the rapid and accurate identification of clinically important microorganisms in clinical laboratories without any preanalysis preparative steps. PMID- 27560301 TI - Assessing neglect dyslexia with compound words. AB - OBJECTIVE: The neglect syndrome is frequently associated with neglect dyslexia (ND), which is characterized by omissions or misread initial letters of single words. ND is usually assessed with standardized reading texts in clinical settings. However, particularly in the chronic phase of ND, patients often report reading deficits in everyday situations but show (nearly) normal performances in test situations that are commonly well-structured. To date, sensitive and standardized tests to assess the severity and characteristics of ND are lacking, although reading is of high relevance for daily life and vocational settings. METHOD: Several studies found modulating effects of different word features on ND. We combined those features in a novel test to enhance test sensitivity in the assessment of ND. Low-frequency words of different length that contain residual pronounceable words when the initial letter strings are neglected were selected. We compared these words in a group of 12 ND-patients suffering from right hemispheric first-ever stroke with word stimuli containing no existing residual words. Finally, we tested whether the serially presented words are more sensitive for the diagnosis of ND than text reading. RESULTS: The severity of ND was modulated strongly by the ND-test words and error frequencies in single word reading of ND words were on average more than 10 times higher than in a standardized text reading test (19.8% vs. 1.8%). CONCLUSION: The novel ND-test maximizes the frequency of specific ND-errors and is therefore more sensitive for the assessment of ND than conventional text reading tasks. (PsycINFO Database Record PMID- 27560302 TI - High kinetic inertness of a bis-hydrated Gd-complex with a constrained AAZTA-like ligand. AB - Kinetic inertness is a key property for a Gd-based contrast agent. The Gd(III) complex of a cyclohexyl-fused AAZTA derivative shows the highest kinetic inertness for non-macrocyclic bis hydrated (q = 2) Gd(III)-complexes with a dissociation half-life of 91 years under physiological conditions, very close to that of macrocyclic clinically approved contrast agents. It also shows optimal relaxometric performance (r1 = 8.3 mM(-1) s(-1) at 20 MHz and 25 degrees C) due to the presence of two inner sphere water molecules in fast exchange with bulk water and not displaced by endogenous anions. PMID- 27560303 TI - Dietary habits, nutrient intake and biomarkers for folate, vitamin D, iodine and iron status among women of childbearing age in Sweden. AB - BACKGROUND: Dietary intake and nutritional status are important for pregnancy and pregnancy outcomes. Dietary advice on folate, targeted to women of childbearing age, aims at preventing neural tube defects in the offspring. AIM: To describe food and nutrient intake and nutritional status among women of childbearing age in Sweden in relation to current nutrition recommendations. METHODS: Dietary intake was assessed using a web-based four-day consecutive food record among adults aged 18-80 years-'Riksmaten 2010-11 adults'. In a subsample, biomarkers of folate, vitamin D, iodine, and iron status were assessed. RESULTS: Women of childbearing age had lower intakes of fruit and vegetables, fish, and whole grains, but higher intakes of soft drinks. Macronutrient composition was generally in line with the Nordic Nutrition Recommendations, except for a lower intake of fibre, a higher intake of saturated fatty acids, and added sugars. Mean intakes of vitamin D, folate, and iron were below recommended intakes (RI). Median urinary iodine concentration (UIC) was 74 MUg/L, 20% had insufficient vitamin D status, and 3% low folate concentrations with no age differences. Furthermore, 29% of women 18-44 years of age had depleted iron stores. CONCLUSIONS: The dietary pattern among women of childbearing age (18-44 years) was less favourable compared to older women. Intakes of some micronutrients were below RI, but no differences in vitamin D, folate, or iodine status between age groups were observed. However, improvements of folate and iodine status among women of childbearing age are warranted. This can be achieved by following dietary guidelines including use of folic acid-containing supplements. PMID- 27560304 TI - A Pilot Study of Strain Elastography in the Diagnosis of Carpal Tunnel Syndrome. AB - PURPOSE: Strain elastography that uses the body's cardiorespiratory pulsations to determine tissue stiffness (referred to here as "ambient strain elastography") has not been previously described for the assessment of carpal tunnel syndrome (CTS). The objective of this study is to assess the reliability of ultrasonographic ambient strain elastography in the evaluation of CTS and compare median nerve stiffness between patients and healthy controls. METHODS: Ambient strain elastography was used to examine the wrists of 17 patients and 26 controls in cross-sectional and longitudinal views, twice by two observers. The strain ratio between the median nerve and nearby tendons was obtained and tested for intrarater and interrater reliability and differences between patients and healthy controls. RESULTS: Intrarater and interrater reliabilities were strong, even for the less experienced rater (lowest r = 0.566, highest r = 0.905; P < 0.001 for all comparisons). No significant difference in strain ratio between those with CTS and controls was detected (cross-sectional image P = 0.32; longitudinal image P = 0.20). Strain ratio did not correlate significantly with traditional ultrasound measures of CTS (lowest P = 0.26) but did correlate significantly with body mass index if obtained from cross-sectional images (r = 0.346; P = 0.02). CONCLUSIONS: This strain elastography method is reliable but does not show changes in median nerve stiffness with CTS. Body mass index may influence elastography and further studies should be conducted to clarify this relationship. PMID- 27560305 TI - Compound Muscle Action Potential Decrement to Repetitive Nerve Stimulation Between Hirayama Disease and Amyotrophic Lateral Sclerosis. AB - PURPOSE: To compare repetitive nerve stimulation (RNS) between Hirayama disease (HD) and amyotrophic lateral sclerosis (ALS). METHODS: The 3-Hz RNS test was performed on bilateral abductor pollicis brevis, abductor digiti minimi, middle deltoid, and upper trapezius muscles in 33 HD patients and 37 ALS patients. RESULTS: In HD patients, none of tested muscles showed any abnormal decrements (>=10%). Significant decrements were observed in 73% of the ALS patients, and decrements were more frequently observed in proximal muscles (deltoid: 70.3%; trapezius: 48.6%). Illness duration did not correlate with decrement percentage in either patient group, and there was no relationship between decrement incidence and ALS diagnostic category (P > 0.05). CONCLUSIONS: The significantly different RNS results between ALS and HD patients support the application of RNS, especially performing RNS in proximal muscles, as a supplementary test in distinguishing these two diseases, even in the early stages. These results may also imply a difference in underlying pathophysiology between ALS and HD. PMID- 27560306 TI - Tailoring Patterns of Surface-Attached Multiresponsive Polymer Networks. AB - A new strategy for the fabrication of micropatterns of surface-attached hydrogels with well-controlled chemistry is reported. The "grafting onto" approach is preferred to the "grafting from" approach. It consists of cross-linking and grafting preformed and functionalized polymer chains through thiol-ene click chemistry. The advantage is a very good control without adding initiators. A powerful consequence of thiol-ene click reaction by UV irradiation is the facile fabrication of micropatterned hydrogel thin films by photolithography. It is achieved either with photomasks using common UV lamp or without photomasks by direct drawing due to laser technology. Our versatile approach allows the fabrication of various chemical polymer networks on various solid substrates. It is demonstrated here with silicon wafers, glass and gold surfaces as substrates, and two responsive hydrogels, poly(N-isopropylacrylamide) for its responsiveness to temperature and poly(acrylic acid) for its pH-sensitivity. We also demonstrate the fabrication of stable hydrogel multilayers (or stacked layers) in which each elementary layer height can widely range from a few nanometers to several micrometers, providing an additional degree of freedom to the internal architecture of hydrogel patterns. This facile route for the synthesis of micrometer-resolute hydrogel patterns with tailored architecture and multiresponsive properties should have a strong impact. PMID- 27560307 TI - Direct Capture of CO2 from Ambient Air. AB - The increase in the global atmospheric CO2 concentration resulting from over a century of combustion of fossil fuels has been associated with significant global climate change. With the global population increase driving continued increases in fossil fuel use, humanity's primary reliance on fossil energy for the next several decades is assured. Traditional modes of carbon capture such as precombustion and postcombustion CO2 capture from large point sources can help slow the rate of increase of the atmospheric CO2 concentration, but only the direct removal of CO2 from the air, or "direct air capture" (DAC), can actually reduce the global atmospheric CO2 concentration. The past decade has seen a steep rise in the use of chemical sorbents that are cycled through sorption and desorption cycles for CO2 removal from ultradilute gases such as air. This Review provides a historical overview of the field of DAC, along with an exhaustive description of the use of chemical sorbents targeted at this application. Solvents and solid sorbents that interact strongly with CO2 are described, including basic solvents, supported amine and ammonium materials, and metal organic frameworks (MOFs), as the primary classes of chemical sorbents. Hypothetical processes for the deployment of such sorbents are discussed, as well as the limited array of technoeconomic analyses published on DAC. Overall, it is concluded that there are many new materials that could play a role in emerging DAC technologies. However, these materials need to be further investigated and developed with a practical sorbent-air contacting process in mind if society is to make rapid progress in deploying DAC as a means of mitigating climate change. PMID- 27560308 TI - Evaluation of Adenosine Triphosphate-Binding Cassette Transporter A1 (ABCA1) R219K and C-Reactive Protein Gene (CRP) +1059G/C Gene Polymorphisms in Susceptibility to Coronary Heart Disease. AB - BACKGROUND This meta-analysis investigated the correlation of ABCA1 R219K and C Reactive Protein Gene (CRP) +1059G/C gene polymorphisms with susceptibility to coronary heart disease (CHD). MATERIAL AND METHODS We searched PubMed, Springer link, Wiley, EBSCO, Ovid, Wanfang database, VIP database, and China National Knowledge Infrastructure (CNKI) databases to retrieve published studies by keyword. Searches were filtered using our stringent inclusion and exclusion criteria. Resultant high-quality data collected from the final selected studies were analyzed using Comprehensive Meta-analysis 2.0 software. Eleven case-control studies involving 3053 CHD patients and 3403 healthy controls met our inclusion criteria. Seven studies were conducted in Asian populations, 3 studies were done in Caucasian populations, and 1 was in an African population. RESULTS Our major finding was that ABCA1 R219K polymorphism increased susceptibility to CHD in allele model (OR=0.729, 95% CI=0.559~0.949, P=0.019) and dominant model (OR=0.698, 95% CI=0.507~0.961, P=0.027). By contrast, we were unable to find any significant association between the CRP +1059G/C polymorphism and susceptibility to CHD (allele model: OR=1.170, 95% CI=0.782~1.751, P=0.444; dominant model: OR=1.175, 95% CI=0.768~1.797, P=0.457). CONCLUSIONS This meta-analysis provides convincing evidence that polymorphism of ABCA1 R219K is associated with susceptibility to CHD while the CRP +1059G/C polymorphism appears to have no correlation with susceptibility to CHD. PMID- 27560309 TI - Lead Oxychloride Borates Obtained under Extreme Conditions. AB - [Pb10O4]Pb2(B2O5)Cl12 (1) and [Pb18O12]Pb(BO2OH)2Cl10 (2) were obtained via high temperature high-pressure experiments. [O12Pb18](12+) and [O4Pb10](12+) oxocentered structural units of different dimensionality are excised from the ideal [OPb] layer in tetragonal alpha-PbO. 2 is formed with an excess of lead oxide component, and 1 is formed with an excess of borate and halide reagents. The structure of 2 can be visualized as the incorporation of {Pb(10)Cl4(BO2OH)2} clusters into alternating PbO and chloride layers, with the existence of square vacancies in both. However, the structure of 1 is described as the intrusion of [O4Pb10](12+) tetramers linked by disordered Pb(B2O5) groups into a halogen three dimensional matrix. The structure of 2 contains 10 symmetrically independent Pb positions. The 6s(2) lone electron pair is stereochemically active on Pb(1)-Pb(9) atoms, whereas it is inert on Pb(10). All of the Pb coordinations in the structure of 2, in accordance with ECCv (volume eccentricity) parameters and the density of states (DOS), can be subdivided into three groups. The current study is the first attempt to analyze this unusual behavior in structurally complex oxyhalide material with the rare case of Pb(2+) cations, demonstrating both stereochemically active and inactive behavior of the lone pair via charge and first-principle calculations. PMID- 27560311 TI - Formation of 1,4,2-Dithiazolidines or 1,3-Thiazetidines from 1,1-Dichloro-2 nitroethene and Phenylthiourea Derivatives. AB - A method for preparation of 1,4,2-dithiazolidine or 1,3-thiazetidine heterocycles was developed by reactions of phenylthioureas with 1,1-dichloro-2-nitroethene. The solvent has a significant influence on the type of product formation. 1,4,2 Dithiazolidines were formed in the aprotic solvent chloroform, while in the protic solvent ethanol, 1,3-thiazetidines were the main products. PMID- 27560310 TI - Biomimetic Hybrid Nanocontainers with Selective Permeability. AB - Chemistry plays a crucial role in creating synthetic analogues of biomacromolecular structures. Of particular scientific and technological interest are biomimetic vesicles that are inspired by natural membrane compartments and organelles but avoid their drawbacks, such as membrane instability and limited control over cargo transport across the boundaries. In this study, completely synthetic vesicles were developed from stable polymeric walls and easy-to engineer membrane DNA nanopores. The hybrid nanocontainers feature selective permeability and permit the transport of organic molecules of 1.5 nm size. Larger enzymes (ca. 5 nm) can be encapsulated and retained within the vesicles yet remain catalytically active. The hybrid structures constitute a new type of enzymatic nanoreactor. The high tunability of the polymeric vesicles and DNA pores will be key in tailoring the nanocontainers for applications in drug delivery, bioimaging, biocatalysis, and cell mimicry. PMID- 27560312 TI - Ultrafast Click Chemistry with Fluorosydnones. AB - We report the synthesis and reactivity of 4-fluorosydnones, a unique class of mesoionic dipoles displaying exquisite reactivity towards both copper-catalyzed and strain-promoted cycloaddition reactions with alkynes. Synthetic access to these new mesoionic compounds was granted by electrophilic fluorination of sigma sydnone Pd(II) precursors in the presence of Selectfluor. Their reactions with terminal and cyclic alkynes were found to proceed very rapidly and selectively, affording 5-fluoro-1,4-pyrazoles with bimolecular rate constants up to 10(4) m( 1) s(-1) , surpassing those documented in the literature with cycloalkynes. Kinetic studies were carried out to unravel the mechanism of the reaction, and the value of 4-fluorosydnones was further highlighted by successful radiolabeling with [(18) F]Selectfluor. PMID- 27560313 TI - New insights into molecular mechanisms of epigenetic regulation in kidney disease. AB - The number of patients with kidney failure has increased in recent years. Different factors contribute to the progression of chronic kidney disease, including glomerular sclerosis, atherosclerosis of the renal arteries and tubulointerstitial fibrosis. Tubulointerstitial injury is induced by hypoxia and other inflammatory signals, leading to fibroblast activation. Technological advances using high-throughput sequencing has enabled the determination of the expression profile of almost all genes, revealing that gene expression is intricately regulated by DNA methylation, histone modification, changes in chromosome conformation, long non-coding RNAs and microRNAs. These epigenetic modifications are stored as cellular epigenetic memory. Epigenetic memory leads to adult-onset disease or ageing in the long term and may possibly play an important role in the kidney disease process. Herein we emphasize the importance of clarifying the molecular mechanisms underlying epigenetic modifications because this may lead to the development of new therapeutic targets in kidney disease. PMID- 27560314 TI - Improving Targeting of Metal-Phenolic Capsules by the Presence of Protein Coronas. AB - Particles adsorb proteins when they enter a physiological environment; this results in a surface coating termed a "protein corona". A protein corona can affect both the properties and functionalities of engineered particles. Here, we prepared hyaluronic acid (HA)-based capsules through the assembly of metal phenolic networks (MPNs) and engineered their targeting ability in the absence and presence of protein coronas by varying the HA molecular weight. The targeting ability of the capsules was HA molecular weight dependent, and a high HA molecular weight (>50 kDa) was required for efficient targeting. The specific interactions between high molecular weight HA capsules and receptor-expressing cancer cells were negligibly affected by the presence of protein coronas, whereas nonspecific capsule-cell interactions were significantly reduced in the presence of a protein corona derived from human serum. Consequently, the targeting specificity of HA-based MPN capsules was enhanced due to the formation of a protein corona. This study highlights the significant and complex roles of a protein corona in biointeractions and demonstrates how protein coronas can be used to improve the targeting specificity of engineered particles. PMID- 27560315 TI - Reporting on Quality Improvement Projects: Where's the Quality? AB - Why so many of these papers are not publishable. PMID- 27560316 TI - Developing a Research Career in Transgender Health. AB - A doctoral scholar describes potential barriers to professional support. PMID- 27560317 TI - Naloxone Administration. PMID- 27560318 TI - Embracing EBP. PMID- 27560319 TI - Minimum Nurse-Patient Ratios. PMID- 27560320 TI - Workplace Violence. PMID- 27560321 TI - Are Nurses Being Nudged Out of Policymaking? AB - Global developments raise questions. PMID- 27560322 TI - Eating Whole Grains Can Reduce Disease and Mortality Risks. AB - The more, the better, but even moderate increases help. PMID- 27560324 TI - Study Assesses the Global Stroke Burden. AB - Modifiable risk factors emerge as leading contributors. PMID- 27560326 TI - Evidence Weak for Antidepressant Use in Children and Adolescents. AB - Drugs have no clear advantages in this population. PMID- 27560330 TI - Spirituality: Part of Nursing Practice, but Too Often Neglected. AB - Nurses need more guidance in addressing spiritual issues with patients. PMID- 27560333 TI - Sumatriptan Patch is Temporarily Suspended. PMID- 27560334 TI - The FDA Revises Boxed Warning For Fluoroquinolones-Again. PMID- 27560338 TI - Recognizing Myocardial Infarction in Women: A Case Study. AB - : The author presents the case of a 52-year-old woman who experienced symptoms of myocardial infarction (MI) over many months; neither her clinicians nor the patient-herself a nurse-recognized them. The author discusses the signs and symptoms of MI in women and highlights how failure to recognize them may lead to misdiagnosis and even death. This case illustrates how important it is that health care providers consider the possibility of heart disease in any woman whose symptoms could be cardiac in origin, even when the cause appears to be something else. PMID- 27560339 TI - Sent Back: Imagining the Real Costs of a Family's End-of-Life Decisions. AB - Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely-and often more personal perspectives on professional, policy, and clinical issues. Best of the Blog will be a regular column to bring AJN readers recent posts that we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com. PMID- 27560340 TI - 'Flipping' the Classroom. AB - This article is one in a series on the roles of adjunct clinical faculty and preceptors, who teach nursing students and new graduates to apply knowledge in clinical settings. This article describes the benefits and challenges of using a "flipped" classroom to promote active engagement among learners and more meaningful interaction between learners and educators. PMID- 27560341 TI - How Can Ward Teaching Be Made More Systematic? AB - : Editor's note: From its first issue in 1900 through to the present day, AJN has unparalleled archives detailing nurses' work and lives over more than a century. These articles not only chronicle nursing's growth as a profession within the context of the events of the day, but they also reveal prevailing societal attitudes about women, health care, and human rights. Today's nursing school curricula rarely include nursing's history, but it's a history worth knowing. To this end, From the AJN Archives highlights articles selected to fit today's topics and times.This month's article, from the June 1926 issue, offers ideas "by which we hope to make ward experiences of more value to the student." Author Mina A. McKay originally presented this material at a meeting of the Massachusetts State League of Nursing Education. She calls for more comprehensive morning and evening reports ("not just a mere reading of... orders"), the use of student experience records, ward clinics ("the type of bedside talk which supplements class room lectures"), and case reports presented by the students themselves. Efforts to improve clinical nursing education are ongoing, and in "'Flipping' the Classroom" in this month's AJN, Diane M. Billings describes a relatively new way of translating clinical concepts into practice. PMID- 27560342 TI - Charting Nursing's Future. AB - A series of policy briefs on topics of interest to nurses. PMID- 27560343 TI - The Effectiveness of Debridement for Venous Leg Ulcers. AB - Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. PMID- 27560344 TI - Legal Considerations in Telehealth and Telemedicine. AB - When engaging in telemedicine, it is important for a nurse to understand legal and regulatory requirements. PMID- 27560345 TI - Acupuncture Relieves Menopause-Related Vasomotor Symptoms. PMID- 27560346 TI - Intensive Blood Pressure Control Lowers Rate of CV Events and Death in the Elderly. PMID- 27560347 TI - New Recommendations for Heart Failure Treatment. PMID- 27560348 TI - Melatonin: Safe And Effective for the Prevention of Migraine Headache. PMID- 27560349 TI - How I Built a Suit of Armor as a Nurse (and Stayed Human). AB - The formation of a resilient professional persona has its pros and cons. PMID- 27560351 TI - Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs. AB - BACKGROUND/AIM: Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. METHODS: Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. RESULTS: Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT were 58.4, 95.8, 93.3 and 69.9%, respectively. CONCLUSIONS: Considering the significant difference in LTT results between the case and control groups in patients receiving carbamazepine and phenytoin, and not observing such a difference in patients receiving phenobarbital and lamotrigine, LTT results are more valuable for the diagnosis of hypersensitivity reactions following the administration of carbamazepine and phenytoin. The LTT has good specificity but low sensitivity for the diagnosis of drug hypersensitivity reactions. PMID- 27560350 TI - Induction and Consolidation of Calcium-Based Homo- and Heterosynaptic Potentiation and Depression. AB - The adaptive mechanisms of homo- and heterosynaptic plasticity play an important role in learning and memory. In order to maintain plasticity-induced changes for longer time scales (up to several days), they have to be consolidated by transferring them from a short-lasting early-phase to a long-lasting late-phase state. The underlying processes of this synaptic consolidation are already well known for homosynaptic plasticity, however, it is not clear whether the same processes also enable the induction and consolidation of heterosynaptic plasticity. In this study, by extending a generic calcium-based plasticity model with the processes of synaptic consolidation, we show in simulations that indeed heterosynaptic plasticity can be induced and, furthermore, consolidated by the same underlying processes as for homosynaptic plasticity. Furthermore, we show that by local diffusion processes the heterosynaptic effect can be restricted to a few synapses neighboring the homosynaptically changed ones. Taken together, this generic model reproduces many experimental results of synaptic tagging and consolidation, provides several predictions for heterosynaptic induction and consolidation, and yields insights into the complex interactions between homo- and heterosynaptic plasticity over a broad variety of time (minutes to days) and spatial scales (several micrometers). PMID- 27560352 TI - Towards Developing an Initial Programme Theory: Programme Designers and Managers Assumptions on the Antiretroviral Treatment Adherence Club Programme in Primary Health Care Facilities in the Metropolitan Area of Western Cape Province, South Africa. AB - BACKGROUND: The antiretroviral adherence club intervention was rolled out in primary health care facilities in the Western Cape province of South Africa to relieve clinic congestion, and improve retention in care, and treatment adherence in the face of growing patient loads. We adopted the realist evaluation approach to evaluate what aspects of antiretroviral club intervention works, for what sections of the patient population, and under which community and health systems contexts, to inform guidelines for scaling up of the intervention. In this article, we report on a step towards the development of a programme theory-the assumptions of programme designers and health service managers with regard to how and why the adherence club intervention is expected to achieve its goals and perceptions on how it has done so (or not). METHODS: We adopted an exploratory qualitative research design. We conducted a document review of 12 documents on the design and implementation of the adherence club intervention, and key informant interviews with 12 purposively selected programme designers and managers. Thematic content analysis was used to identify themes attributed to the programme actors, context, mechanisms, and outcomes. Using the context-mechanism outcome configurational tool, we provided an explanatory focus of how the adherence club intervention is roll-out and works guided by the realist perspective. RESULTS: We classified the assumptions of the adherence club designers and managers into the rollout, implementation, and utilisation of the adherence club programme, constructed around the providers, management/operational staff, and patients, respectively. Two rival theories were identified at the patient-perspective level. We used these perspectives to develop an initial programme theory of the adherence club intervention, which will be tested in a later phase. CONCLUSION: The perspectives of the programme designers and managers provided an important step towards developing an initial programme theory, which will guide our realist evaluation of the adherence club programme in South Africa. PMID- 27560353 TI - Chromosomal polymorphic variants increase aneuploidies in male gametes and embryos. AB - Chromosomal polymorphisms involve heterochromatic regions and occur in the general population. However, previous studies have reported a higher incidence of these variants in infertile patients. The aim of this study was to examine the relationship between polymorphic variants and infertility and their association with aneuploidies in male gametes and embryos. We retrospectively considered 1,551 cytogenetic studies involving infertile patients (study group; n=866) and oocyte/sperm donors as the control group (n=685). We had detected 168 polymorphisms in the study group and 92 in the control group. An increase in the frequency of polymorphic variants was observed among infertile patients (19.4% study group vs. 13.4% control group; P < 0.01). Sperm aneuploidies among 145 infertile men were evaluated by fluorescent in situ hybridization (FISH). The frequency of infertile men with increased rates of sperm aneuploidy was higher among polymorphism carriers. Twenty men showed an abnormal rate of sperm aneuploidy in the carrier group (n=53) vs. 15 in the non-carrier group (n=92) (37.7% vs. 16.3%, respectively; P < 0.01). Finally, aneuploidies in blastocysts (n=301) resulting from donated oocytes were also examined by array comparative genomic hybridization (array-CGH). Significant differences were reported in the embryo aneuploidy rate between female carriers and non-carriers in oocyte donation cycles (50.0% vs. 27.6%; P < 0.001). This study suggests that polymorphic variants have an impact on fertility. Moreover, our results show a relationship between polymorphisms and aneuploidy in spermatozoa and embryos. ABBREVIATIONS: FISH: fluorescent in situ hybridization; CGH: comparative genomic hybridization; ESHRE: European Society of Human Reproduction and Embryology; ASRM: American Society for Reproductive Medicine; RPL: recurrent pregnancy loss; WHO: World Health Organization; ISCN: International System for Human Cytogenetic Nomenclature guidelines; WGA: whole genome amplification; SPSS: Statistical Package for Social Sciences. PMID- 27560354 TI - A DOTA based bisphosphonate with an albumin binding moiety for delayed body clearance for bone targeting. AB - Radiolabeled bisphosphonates are commonly used in the diagnosis and therapy of bone metastases. Blood clearance of bisphosphonates is usually fast and only 30% 50% of the injected activity is retained in the skeleton, while most of the activity is excreted by the urinary tract. A longer blood circulation may enhance accumulation of bisphosphonate compounds in bone metastases. Therefore, a chemically modified macrocyclic bisphosphonate derivative with an additional human albumin binding entity was synthesized and pharmacokinetics of its complex was evaluated. The DOTA-bisphosphonate conjugate BPAMD was compared against the novel DOTAGA-derived albumin-binding bisphosphonate DOTAGA(428-d-Lys)MBP (L1). The ligands were labeled with 68Ga(III) and were evaluated in in vitro binding studies to hydroxyapatite (HA) as well as to human serum albumin. The compounds were finally compared in in vivo PET and ex vivo organ distribution studies in small animals over 6h. Binding studies revealed a consistent affinity of both bisphosphonate tracers to HA. Small animal PET and ex vivo organ distribution studies showed longer blood retention of [68Ga]L1. [68Ga]BPAMD is initially more efficiently bound to the bone but skeletal accumulation of the modified compound and [68Ga]BPAMD equalized at 6h p.i. Ratios of femur epiphyseal plate to ordinary bone showed to be more favorable for [68Ga]L1 than for [68Ga]BPAMD due to the longer circulation time of the new tracer. Thus, the chemical modification of BPAMD toward an albumin-binding bisphosphonate, L1, resulted in a novel PET tracer which conserves advantages of both functional groups within one and the same molecule. The properties of this new diagnostic tracer are expected to be preserved in 177Lu therapeutic agent with the same ligand (a theranostic pair). PMID- 27560355 TI - Pressure Dependence of Hydrogen-Bond Dynamics in Liquid Water Probed by Ultrafast Infrared Spectroscopy. AB - Clarifying the structure/dynamics relation of water hydrogen-bond network has been the aim of extensive research over many decades. By joining anvil cell high pressure technology, femtosecond 2D infrared spectroscopy, and molecular dynamics simulations, we studied, for the first time, the spectral diffusion of the stretching frequency of an HOD impurity in liquid water as a function of pressure. Our experimental and simulation results concordantly demonstrate that the rate of spectral diffusion is almost insensitive to the applied pressure. This behavior is in contrast with the previously reported pressure-induced speed up of the orientational dynamics, which can be rationalized in terms of large angular jumps involving sudden switching between two hydrogen-bonded configurations. The different trend of the spectral diffusion can be, instead, inferred considering that the first solvation shell preserves the tetrahedral structure with pressure and the OD stretching frequency is only slight perturbed. PMID- 27560356 TI - Adult Neurogenesis in Mammals: Variations and Confusions. AB - Mammalian adult neurogenesis has remained enigmatic. Two lines of research have emerged. One focuses on a potential repair mechanism in the human brain. The other aims at elucidating its functional role in the hippocampal formation, chiefly in cognitive processes; however, thus far it has been unsuccessful. Here, we try to recognize the sources of errors and conceptual confusion in comparative studies and neurobehavioral approaches with a focus on mice. Evolutionarily, mammalian adult neurogenesis appears as protracted juvenile neurogenesis originating from precursor cells in the secondary proliferation zones, from where newly formed cells migrate to target regions in the forebrain. This late developmental process is downregulated differentially in various brain structures depending on species and age. Adult neurogenesis declines substantially during early adulthood and persists at low levels into senescence. Short-lasting episodes in proliferation or reduction of adult neurogenesis may reflect a multitude of factors, and have been studied chiefly in mice and rats. Comparative studies face both species-specific variations in staining and technical abilities of laboratories, lacking quantification of important reference measures (e.g. granule cell number) and evaluation of maturational markers whose persistence might be functionally more relevant than proliferation rates. Likewise, the confusion about the functional role of variations in adult hippocampal neurogenesis has many causes. Prominent is an inferential statistical approach, usually with low statistical power. Interpretation is complicated by multiple theories about hippocampal function, often unrealistically extrapolating from humans to rodents. We believe that the field of mammalian adult neurogenesis needs more critical thinking, more sophisticated hypotheses, better statistical, technical and behavioral approaches, and a broader conceptual perspective incorporating comparative aspects rather than neglecting them. PMID- 27560357 TI - Steric versus electronic factors in metallacarborane isomerisation: nickelacarboranes with 3,1,2-, 4,1,2- and 2,1,8-NiC2B9 architectures and pendant carborane groups, derived from 1,1'-bis(o-carborane). AB - Metalation of the [7-(1'-1',2'-closo-C2B10H11)-7,8-nido-C2B9H10](2-) dianion with various {NiPP(2+)} or {NiP2(2+)} fragments (PP = chelating diphosphine; P = monodentate phosphine or phosphite) leads either to unisomerised 3,1,2-NiC2B9 species or to isomerised 4,1,2-NiC2B9 or 2,1,8-NiC2B9 species, all with a pendant C2B10 substituent. The products [1-(1'-1',2'-closo-C2B10H11)-3-dppe-3,1,2-closo NiC2B9H10] (1), [2-(1'-1',2'-closo-C2B10H11)-4-dppe-4,1,2-closo-NiC2B9H10] (2), [8-(1'-1',2'-closo-C2B10H11)-2-dmpe-2,1,8-closo-NiC2B9H10] (3), [1-(1'-1',2' closo-C2B10H11)-3,3-(PMe3)2-3,1,2-closo-NiC2B9H10] (4), [1-(1'-1',2'-closo C2B10H11)-3,3-(PMe2Ph)2-3,1,2-closo-NiC2B9H10] (6), [1-(1'-1',2'-closo-C2B10H11) 3,3-{P(OMe)3}2-3,1,2-closo-NiC2B9H10] (9) and [1-(1'-1',2'-closo-C2B10H11)-2,2 {P(OMe)3}2-2,1,8-closo-NiC2B9H10] (10) were fully characterised spectroscopically and crystallographically, whilst [2-(1'-1',2'-closo-C2B10H11)-4,4-(PMePh2)2-4,1,2 closo-NiC2B9H10] (8) was characterised spectroscopically. Overall the results suggest that an important factor in a 3,1,2 to 4,1,2 isomerisation is the relief gained from steric crowding, whereas a 3,1,2 to 2,1,8 isomerisation appears to be favoured by strongly electron-donating ligands on the metal. PMID- 27560359 TI - Facet-controlled anatase TiO2 nanoparticles through various fluorine sources for superior photocatalytic activity. AB - Reactive surface-exposed anatase TiO2 (a-TiO2) is highly desirable for applications requiring superior photocatalytic activity. In order to obtain a favorable surface, morphology control of the a-TiO2 using capping agents has been widely investigated. Herein, we systematically study the effects of different F sources (HF, TiF4, and NH4F) as the capping agent on the morphology control and photocatalytic activities of a-TiO2 in a hydrothermal process. When either HF or TiF4 was added, large truncated bipyramids formed with the photocatalytically active {001} facet, whereas the NH4F was not effective for facet control, yielding nanospheres similar to the pure a-TiO2. The morphology changes were related to the decomposition behaviors of the F sources in the solvent material: HF and TiF4 decomposed and supplied F(-) ions before a-TiO2 nucleation, which changed the nucleation rate and growth direction, leading to the resultant a-TiO2 morphology. On the other hand, NH4F supplied F(-) ions after a-TiO2 nucleation and could not change the growth behavior. In terms of the photocatalytic effect, the HF- and TiF4-treated a-TiO2 effectively decomposed ~90% and ~80% of methylene blue, respectively, in 1 h, while ~60% was decomposed for the NH4F-treated a TiO2. Note that pure a-TiO2 photocatalytically decomposed only ~10% of methylene blue over the same time. These results pave the way to precise control of the facet of TiO2 through using different capping agents. PMID- 27560360 TI - Sero-Molecular Epidemiology of Japanese Encephalitis in Zhejiang, an Eastern Province of China. AB - BACKGROUND: Sporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains. METHODOLOGY/PRINCIPAL FINDINGS: A total of 570 serum specimens were sampled from community population aged from 0 to 92 years old in Xianju county of Zhejiang Province in 2013-2014. Microseroneutralization test results were analyzed to estimate the population immunity and to observe antibody dynamics in vaccinated children. E genes of 28 JEV strains isolated in Zhejiang Province were sequenced for phylogenetic tree construction and molecular characteristics analysis with other selected strains. Positive JE neutralizing antibody rates were higher in residents >=35 years old (81%~98%) and lower in residents <35 years old (0~57%). 7 or 8 years after the 2nd live attenuated vaccine dose, the antibodies against for 4 different strains with microseroneutralization test were decreased by 55%~73% on seropositive rates and by 25%~38% on GMTs respectively. JEV strains isolated in recent years were all grouped into GI, while those isolated in the 1980s belonged to GIII. On important amino acid sites related to antigenicity, there was no divergence between the Zhejiang JE virus strains and the vaccine strain (SA14-14-2). CONCLUSION/SIGNIFICANCES: JE neutralizing antibody positive rates increase in age >=10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically. PMID- 27560362 TI - Influence of a Trematode Parasite (Microphallus turgidus) on Grass Shrimp ( Palaemonetes pugio ) Response to Refuge and Predator Presence. AB - The grass shrimp ( Palaemonetes pugio ) is a staple prey species in the diet of many ecologically and economically important species such as blue crab and striped bass and is commonly infected with a trematode parasite, Microphallus turgidus. To complete its life cycle, M. turgidus must be consumed as a metacercaria by a bird or mammal definitive host. Previous research has found that infected grass shrimp behave more conspicuously than uninfected shrimp around predators, which include mummichogs ( Fundulus heteroclitus ). In addition, grass shrimp are more likely to avoid predation when they have access to coarse woody debris (CWD). Aquaria experiments revealed that uninfected shrimp significantly reduce the amount of time spent swimming in the presence of a fish predator, whereas infected shrimp did not exhibit this predation avoidance behavior. Uninfected shrimp also increased predator avoidance behavior ("backthrusts") in the absence of CWD, whereas infected shrimp did not. These findings suggest that M. turgidus does not influence grass shrimp usage of CWD, but it alters shrimp swimming and backthrust behavior, thereby rendering infected shrimp more susceptible to predation. The implications of increased predation by a fish (nonhost or possible paratenic host) versus by a bird or mammal (definitive host) for parasite transmission are discussed. PMID- 27560361 TI - The Role of the Subgenual Anterior Cingulate Cortex and Amygdala in Environmental Sensitivity to Infant Crying. AB - Newborns and infants communicate their needs and physiological states through crying and emotional facial expressions. Little is known about individual differences in responding to infant crying. Several theories suggest that people vary in their environmental sensitivity with some responding generally more and some generally less to environmental stimuli. Such differences in environmental sensitivity have been associated with personality traits, including neuroticism. This study investigated whether neuroticism impacts neuronal, physiological, and emotional responses to infant crying by investigating blood-oxygenation-level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI) in a large sample of healthy women (N = 102) with simultaneous skin conductance recordings. Participants were repeatedly exposed to a video clip that showed crying infants and emotional responses (valence, arousal, and irritation) were assessed after every video clip presentation. Increased BOLD signal during the perception of crying infants was found in brain regions that are associated with emotional responding, the amygdala and anterior insula. Significant BOLD signal decrements (i.e., habituation) were found in the fusiform gyrus, middle temporal gyrus, superior temporal gyrus, Broca's homologue on the right hemisphere, (laterobasal) amygdala, and hippocampus. Individuals with high neuroticism showed stronger activation in the amygdala and subgenual anterior cingulate cortex (sgACC) when exposed to infant crying compared to individuals with low neuroticism. In contrast to our prediction we found no evidence that neuroticism impacts fMRI-based measures of habituation. Individuals with high neuroticism showed elevated skin conductance responses, experienced more irritation, and perceived infant crying as more unpleasant. The results support the hypothesis that individuals high in neuroticism are more emotionally responsive, experience more negative emotions, and may show enhanced cognitive control during the exposure to infant distress, which may impact infant-directed behavior. PMID- 27560363 TI - Fast detection of deletion breakpoints using quantitative PCR. AB - The routine detection of large and medium copy number variants (CNVs) is well established. Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization. These methods only map deleted or duplicated exons, without providing the exact location of breakpoints. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Here, we present a strategy for detecting the breakpoints of medium and large CNVs regardless of their size. The hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. The strategy is fast, reliable and cost-efficient, making it amenable to widespread use in genetic laboratories. PMID- 27560364 TI - Lack of functional KL-VS polymorphism of the KLOTHO gene in the Korean population. AB - The functional variant of the Klotho "KL-VS" stretch, which includes six polymorphisms in linkage disequilibrium, is reportedly associated with healthy aging and longevity in European and American populations. Among Asian populations, this variant has been observed in the Indian population but not in the Iranian population. An association between KL-VS polymorphism and aging has not been reported in Koreans. To investigate whether the KL-VS polymorphism could be associated with healthy aging and longevity in a Korean population, we analyzed genotype and allele frequencies of the KL-VS variant in a large Korean population sample. The KL-VS variant was not found in 874 Korean individuals. Thus, it is not possible to test its association to aging in the East Asian populations. PMID- 27560366 TI - Aortic dissection. PMID- 27560365 TI - Physiological Perturbation Reveals Modularity of Eyespot Development in the Painted Lady Butterfly, Vanessa cardui. AB - Butterfly eyespots are complex morphological traits that can vary in size, shape and color composition even on the same wing surface. Homology among eyespots suggests they share a common developmental basis and function as an integrated unit in response to selection. Despite strong evidence of genetic integration, eyespots can also exhibit modularity or plasticity, indicating an underlying flexibility in pattern development. The extent to which particular eyespots or eyespot color elements exhibit modularity or integration is poorly understood, particularly following exposure to novel conditions. We used perturbation experiments to explore phenotypic correlations among different eyespots and their color elements on the ventral hindwing of V. cardui. Specifically, we identified which eyespots and eyespot features are most sensitive to perturbation by heat shock and injection of heparin-a cold shock mimic. For both treatments, the two central eyespots (3 + 4) were most affected by the experimental perturbations, whereas the outer eyespot border was more resistant to modification than the interior color elements. Overall, the individual color elements displayed a similar response to heat shock across all eyespots, but varied in their response to each other. Graphical modeling also revealed that although eyespots differ morphologically, regulation of eyespot size and colored elements appear to be largely integrated across the wing. Patterns of integration, however, were disrupted following heat shock, revealing that the strength of integration varies across the wing and is strongest between the two central eyespots. These findings support previous observations that document coupling between eyespots 3 + 4 in other nymphalid butterflies. PMID- 27560367 TI - Synergistic effect of cellulase and xylanase during hydrolysis of natural lignocellulosic substrates. AB - Synergistic combination of cellulase and xylanase has been performed on pre treated substrates in many previous studies, while few on natural substrates. In this study, three unpretreated lignocellulosic substrates were studied, including corncob, corn stover, and rice straw. The results indicated that when the mixed cellulase and xylanase were applied, reducing sugar concentrations were calculated as 19.53, 15.56, and 17.35mg/ml, respectively, based on the 3,5 dinitrosalicylic acid (DNS) method. Compared to the treatment with only cellulose, the hydrolysis yields caused by mixed cellulase and xylanase were improved by 133%, 164%, and 545%, respectively. In addition, the conversion yield of corncob, corn stover, and rice straw by cellulase-xylanase co-treatment reached 43.9%, 48.5%, and 40.2%, respectively, based on HPLC analysis, which confirmed the synergistic effect of cellulase-xylanase that was much higher than either of the single enzyme treatment. The substrate morphology was also evaluated to explore the synergistic mechanism of cellulase-xylanase. PMID- 27560369 TI - Drosophila yakuba mayottensis, a new model for the study of incipient ecological speciation. AB - A full understanding of how ecological factors drive the fixation of genetic changes during speciation is obscured by the lack of appropriate models with clear natural history and powerful genetic toolkits. In a recent study, we described an early stage of ecological speciation in a population of the generalist species Drosophila yakuba (melanogaster subgroup) on the island of Mayotte (Indian Ocean). On this island, flies are strongly associated with the toxic fruits of noni (Morinda citrifolia) and show a partial degree of pre zygotic reproductive isolation. Here, I mine the nuclear and mitochondrial genomes and provide a full morphological description of this population. Only 29 nuclear sites (< 4 * 10-7 of the genome) are fixed in this population and absent from 3 mainland populations and the closest relative D. santomea, but no mitochondrial or morphological character distinguish Mayotte flies from the mainland. This result indicates that physiological and behavioral traits may evolve faster than morphology at the early stages of speciation. Based on these differences, the Mayotte population is designated as a new subspecies, Drosophila yakuba mayottensis subsp. nov., and its strong potential in understanding the genetics of speciation and plant-insect interactions is discussed. PMID- 27560368 TI - The Role of Global and Local Visual Information during Gaze-Cued Orienting of Attention. AB - Gaze direction is an important social communication tool. Global and local visual information are known to play specific roles in processing socially relevant information from a face. The current study investigated whether global visual information has a primary role during gaze-cued orienting of attention and, as such, may influence quality of interaction. Adults performed a gaze-cueing task in which a centrally presented face cued (valid or invalid) the location of a peripheral target through a gaze shift. We measured brain activity (electroencephalography) towards the cue and target and behavioral responses (manual and saccadic reaction times) towards the target. The faces contained global (i.e. lower spatial frequencies), local (i.e. higher spatial frequencies), or a selection of both global and local (i.e. mid-band spatial frequencies) visual information. We found a gaze cue-validity effect (i.e. valid versus invalid), but no interaction effects with spatial frequency content. Furthermore, behavioral responses towards the target were in all cue conditions slower when lower spatial frequencies were not present in the gaze cue. These results suggest that whereas gaze-cued orienting of attention can be driven by both global and local visual information, global visual information determines the speed of behavioral responses towards other entities appearing in the surrounding of gaze cue stimuli. PMID- 27560371 TI - Sibship Size and Gendered Resource Dilution in Different Societal Contexts. AB - Resource dilution theory hypothesizes that children's educational attainment suffers from being raised with many siblings, as the parental resources have to be shared with more children. Based on economic and cultural theories, we hypothesize that resource dilution is gendered: especially a larger number of brothers is harmful to a person's educational attainment. Using the Survey of Health, Ageing and Retirement in Europe, covering 18 European countries, we show that the number of brothers is more negatively related with the odds of obtaining a college degree than the number of sisters. This holds particularly for women. However, this pattern is weaker in countries that are known to have a more gender egalitarian climate. PMID- 27560370 TI - Hras helps hippo heterodimerize to evade tumor suppression. AB - Ras oncoproteins can promote or suppress cellular apoptosis, but the mechanisms underlying these varied responses remain incompletely understood. Ras is linked to the Hippo tumor suppressor pathway, a highly conserved signaling cassette that regulates organ size in animals ranging from flies to humans. The proximal members of this pathway, Mammalian Ste20-like kinases (Msts) -1 and -2, self associate in homodimers and also form heterodimers with other proteins. Formation of such complexes is known to regulate Mst kinase activity and thus, the Hippo pathway. In a manuscript that recently appeared in Current Biology, we showed that activated Hras promotes the formation of Mst1/Mst2 heterodimers, that activation of Erk was required for this event, and that these heterodimers were much less active than Mst1/Mst1 or Mst2/Mst2 homodimers. Interestingly, the formation of such heterodimers was required to deactivate the Hippo pathway and to enable transformation by Hras. In this Commentary, we discuss the background for this study and surprising implications thereof. PMID- 27560372 TI - D186/D190 is an allele-dependent determinant of HIV-1 Nef function. AB - The HIV-1 pathogenesis factor Nef interacts with numerous ligands to affect cellular vesicular transport, signal transduction and cytoskeletal dynamics. While most Nef functions depend on multivalent protein interaction motifs, disrupting actin dynamics requires a motif that specifically recruits the host kinase PAK2. An adjacent aspartate was recently predicted to mediate Nef-beta catenin interactions. We report here that beta-catenin can be co immunoprecipitated with Nef.GFP from Jurkat T cell lysates. This association is conserved among lentiviral Nef proteins but does not involve classical Nef protein interaction motifs, including the critical aspartate. While aspartate-to alanine mutations impaired cell surface receptor downregulation and interference with actin dynamics and cell motility by HIV-1 NA7 Nef, analogous mutations did not affect HIV-1 SF2 Nef function. These allelic differences were determined by a proximal lysine/arginine polymorphism. These results emphasize differences between Nef alleles regarding the functional role of individual residues and underscore the need for allele-specific structure-function analyses. PMID- 27560373 TI - Interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection. AB - The immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IkappaB degradation and activation of NF-kappaB. We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-gamma-dependent manner. Absence of the beta5i immunoproteasome subunit and pharmacological inhibition of beta5i activity had minimal effects on viral replication, virus induced cellular inflammation, or induction of cytokine expression. Likewise, the establishment of protective immunity following primary infection was not significantly altered by beta5i deficiency. Thus, although immunoproteasome activity is robustly induced during acute infection with MAV-1, our data suggest that other mechanisms are capable of compensating for immunoproteasome activity to maintain antiviral immunity and appropriate inflammatory responses. PMID- 27560375 TI - Surgical Treatment For T4 Oropharyngeal Cancer-Reply. PMID- 27560374 TI - Correction: The Impact of Genetic Relationship and Linkage Disequilibrium on Genomic Selection. AB - [This corrects the article DOI: 10.1371/journal.pone.0132379.]. PMID- 27560376 TI - A Comprehensive Analysis of Plasmodium Circumsporozoite Protein Binding to Hepatocytes. AB - Circumsporozoite protein (CSP) is the dominant protein on the surface of Plasmodium sporozoites and plays a critical role in the invasion by sporozoites of hepatocytes. Contacts between CSP and heparin sulfate proteoglycans (HSPGs) lead to the attachment of sporozoites to hepatocytes and trigger signaling events in the parasite that promote invasion of hepatocytes. The precise sequence elements in CSP that bind HSPGs have not been identified. We performed a systematic in vitro analysis to dissect the association between Plasmodium falciparum CSP (PfCSP) and hepatocytes. We demonstrate that interactions between PfCSP and heparin or a cultured hepatoma cell line, HepG2, are mediated primarily by a lysine-rich site in the amino terminus of PfCSP. Importantly, the carboxyl terminus of PfCSP facilitates heparin-binding by the amino-terminus but does not interact directly with heparin. These findings provide insights into how CSP recognizes hepatocytes and useful information for further functional studies of CSP. PMID- 27560377 TI - Association of Sjogrens Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis. AB - OBJECTIVE: The association between Sjogren's syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case control study to evaluate the associations between SS and HBV and HCV infections. MATERIALS AND METHODS: We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (<55 and >=55 years) risks of SS were evaluated. RESULTS: The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (OR = 2.49, 95% CI = 2.16-2.86). Conversely, HBV infection was not associated with SS (OR = 1.10, 95% CI = 0.98-1.24). Younger HCV patients were at a higher risk for SS (<55 years: OR = 3.37, 95% CI = 2.62-4.35; >=55 years: OR = 2.20, 95% CI = 1.84-2.62). Men with HCV were at a greater risk for SS (women: OR = 2.26, 95% CI = 1.94-2.63; men: OR = 4.22, 95% CI = 2.90 6.16). Only men with chronic HBV exhibited a higher risk of SS (OR = 1.61, 95% CI = 1.21-2.14). CONCLUSION: HCV infection was associated with SS; however, HBV only associated with SS in men. PMID- 27560379 TI - Correction: Insights into How Longicorn Beetle Larvae Determine the Timing of Metamorphosis: Starvation-Induced Mechanism Revisited. AB - [This corrects the article DOI: 10.1371/journal.pone.0158831.]. PMID- 27560378 TI - From Sensory Perception to Lexical-Semantic Processing: An ERP Study in Non Verbal Children with Autism. AB - This study examines electrocortical activity associated with visual and auditory sensory perception and lexical-semantic processing in nonverbal (NV) or minimally verbal (MV) children with Autism Spectrum Disorder (ASD). Currently, there is no agreement on whether these children comprehend incoming linguistic information and whether their perception is comparable to that of typically developing children. Event-related potentials (ERPs) of 10 NV/MV children with ASD and 10 neurotypical children were recorded during a picture-word matching paradigm. Atypical ERP responses were evident at all levels of processing in children with ASD. Basic perceptual processing was delayed in both visual and auditory domains but overall was similar in amplitude to typically-developing children. However, significant differences between groups were found at the lexical-semantic level, suggesting more atypical higher-order processes. The results suggest that although basic perception is relatively preserved in NV/MV children with ASD, higher levels of processing, including lexical- semantic functions, are impaired. The use of passive ERP paradigms that do not require active participant response shows significant potential for assessment of non-compliant populations such as NV/MV children with ASD. PMID- 27560380 TI - A Systematic Review of Predictions of Survival in Palliative Care: How Accurate Are Clinicians and Who Are the Experts? AB - BACKGROUND: Prognostic accuracy in palliative care is valued by patients, carers, and healthcare professionals. Previous reviews suggest clinicians are inaccurate at survival estimates, but have only reported the accuracy of estimates on patients with a cancer diagnosis. OBJECTIVES: To examine the accuracy of clinicians' estimates of survival and to determine if any clinical profession is better at doing so than another. DATA SOURCES: MEDLINE, Embase, CINAHL, and the Cochrane Database of Systematic Reviews and Trials. All databases were searched from the start of the database up to June 2015. Reference lists of eligible articles were also checked. ELIGIBILITY CRITERIA: INCLUSION CRITERIA: patients over 18, palliative population and setting, quantifiable estimate based on real patients, full publication written in English. EXCLUSION CRITERIA: if the estimate was following an intervention, such as surgery, or the patient was artificially ventilated or in intensive care. STUDY APPRAISAL AND SYNTHESIS METHODS: A quality assessment was completed with the QUIPS tool. Data on the reported accuracy of estimates and information about the clinicians were extracted. Studies were grouped by type of estimate: categorical (the clinician had a predetermined list of outcomes to choose from), continuous (open-ended estimate), or probabilistic (likelihood of surviving a particular time frame). RESULTS: 4,642 records were identified; 42 studies fully met the review criteria. Wide variation was shown with categorical estimates (range 23% to 78%) and continuous estimates ranged between an underestimate of 86 days to an overestimate of 93 days. The four papers which used probabilistic estimates tended to show greater accuracy (c-statistics of 0.74-0.78). Information available about the clinicians providing the estimates was limited. Overall, there was no clear "expert" subgroup of clinicians identified. LIMITATIONS: High heterogeneity limited the analyses possible and prevented an overall accuracy being reported. Data were extracted using a standardised tool, by one reviewer, which could have introduced bias. Devising search terms for prognostic studies is challenging. Every attempt was made to devise search terms that were sufficiently sensitive to detect all prognostic studies; however, it remains possible that some studies were not identified. CONCLUSION: Studies of prognostic accuracy in palliative care are heterogeneous, but the evidence suggests that clinicians' predictions are frequently inaccurate. No sub-group of clinicians was consistently shown to be more accurate than any other. IMPLICATIONS OF KEY FINDINGS: Further research is needed to understand how clinical predictions are formulated and how their accuracy can be improved. PMID- 27560381 TI - Comparison of Normal and Pre-Eclamptic Placental Gene Expression: A Systematic Review with Meta-Analysis. AB - Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30% of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae. We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in the molecular pathology of the disease. PMID- 27560382 TI - A Novel SCN5A Mutation Associated with Drug Induced Brugada Type ECG. AB - BACKGROUND: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the alpha-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. OBJECTIVE: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. METHODS: Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study. Genetic screening using direct sequencing identified a novel SCN5A variant, p.V1328M. Electrophysiological parameters of WT and p.V1328M and their effects on drug pharmacokinetics were studied using the patch-clamp method. RESULTS: Whole-cell sodium current densities were similar for WT and p.V1328M channels. While p.V1328M mutation did not affect the voltage-dependence of the activation kinetics, it caused a positive shift of voltage-dependent steady-state inactivation by 7 mV. The tonic block in the presence of pilsicainide was similar in WT and p.V1328M, when sodium currents were induced by a low frequency pulse protocol (q15s). On the contrary, p.V1328M mutation enhanced pilsicainide induced use-dependent block at 2 Hz. (Ki: WT, 35.8 MUM; V1328M, 19.3 MUM). CONCLUSION: Our study suggests that a subclinical SCN5A mutation, p.V1328M, might predispose individuals harboring it to drug-induced Brugada Syndrome. PMID- 27560384 TI - On the Role of Neurogenesis and Neural Plasticity in the Evolution of Animal Personalities and Stress Coping Styles. AB - Individual variation in how animals react to stress and environmental change has become a central topic in a wide range of biological disciplines, from evolutionary ecology to biomedicine. Such variation manifests phenotypically as correlated trait-clusters (referred to as coping styles, behavioral syndromes, shyness-boldness, or personality traits). Thresholds for switching from active coping (fight-flight) to inhibition and passive behavior when exposed to stress depend on experience and genetic factors. Comparative research has revealed a range of neuroendocrine-behavioral associations which are conserved throughout the vertebrate subphylum, including factors affecting perception, learning, and memory of stimuli and events. Here we review conserved aspects of the contribution of neurogenesis and other aspects of neural plasticity to stress coping. In teleost fish, brain cell proliferation and neurogenesis have received recent attention. This work reveals that brain cell proliferation and neurogenesis are associated with heritable variation in stress coping style, and they are also differentially affected by short- and long-term stress in a biphasic manner. Routine-dependent and inflexible behavior in proactive individuals is associated with limited neural plasticity. These evolutionarily conserved relationships hold the potential to illuminate the biological background for stress-related neurobiological disorders. PMID- 27560385 TI - A grapevine cytochrome P450 generates the precursor of wine lactone, a key odorant in wine. AB - Monoterpenes are important constituents of the aromas of food and beverages, including wine. Among monoterpenes in wines, wine lactone has the most potent odor. It was proposed to form via acid-catalyzed cyclization of (E)-8 carboxylinalool during wine maturation. It only reaches very low concentrations in wine but its extremely low odor detection threshold makes it an important aroma compound. Using LC-MS/MS, we show here that the (E)-8-carboxylinalool content in wines correlates with their wine lactone content and estimate the kinetic constant for the very slow formation of wine lactone from (E)-8 carboxylinalool. We show that (E)-8-carboxylinalool is accumulated as a glycoside in grape (Vitis vinifera) berries and that one of the cytochrome P450 enzymes most highly expressed in maturing berries, CYP76F14, efficiently oxidizes linalool to (E)-8-carboxylinalool. Our analysis of (E)-8-carboxylinalool in Riesling * Gewurztraminer grapevine progeny established that the CYP76F14 gene co locates with a quantitative trait locus for (E)-8-carboxylinalool content in grape berries. Our data support the role of CYP76F14 as the major (E)-8 carboxylinalool synthase in grape berries and the role of (E)-8-carboxylinalool as a precursor to wine lactone in wine, providing new insights into wine and grape aroma metabolism, and new methods for food and aroma research and production. PMID- 27560383 TI - Noncommutative Biology: Sequential Regulation of Complex Networks. AB - Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome. We showed that with noncommutative control, it is possible to independently control targets that would otherwise be activated simultaneously using combinatorial logic. Consequently, sequential logic overcomes the information bottleneck inherent in complex networks. We derived scaling laws for two noncommutative models of regulation, motivated by phosphorylation/neural networks and chromosome folding, respectively, and showed that they scale super exponentially in the number of regulators. We also showed that specificity in control is robust to the loss of a regulator. Lastly, we connected these theoretical results to real biological networks that demonstrate specificity in the context of promiscuity. These results show that achieving a desired outcome often necessitates roundabout steps. PMID- 27560386 TI - Purification, Conformational Analysis, and Properties of a Family of Tigerinin Peptides from Skin Secretions of the Crowned Bullfrog Hoplobatrachus occipitalis. AB - Four host-defense peptides belonging to the tigerinin family (tigerinin-1O: RICTPIPFPMCY; tigerinin-2O: RTCIPIPLVMC; tigerinin-3O: RICTAIPLPMCL; and tigerinin-4O: RTCIPIPPVCF) were isolated from skin secretions of the African crowned bullfrog Hoplobatrachus occipitalis. In aqueous solution at pH 4.8, the cyclic domain of tigerinin-2O adopts a rigid amphipathic conformation that incorporates a flexible N-terminal tail. The tigerinins lacked antimicrobial (MIC > 100 MUM) and hemolytic (LC50 > 500 MUM) activities but, at a concentration of 20 MUg/mL, significantly (P < 0.05) inhibited production of interferon-gamma (IFN gamma) by peritoneal cells from C57BL/6 mice without affecting production of IL 10 and IL-17. Tigerinin-2O and -4O inhibited IFN-gamma production at concentrations as low as 1 MUg/mL. The tigerinins significantly (P <= 0.05) stimulated the rate of insulin release from BRIN-BD11 clonal beta-cells without compromising the integrity of the plasma membrane. Tigerinin-1O was the most potent (threshold concentration 1 nM) and the most effective (395% increase over basal rate at a concentration of 1 MUM). Tigerinin-4O was the most potent and effective peptide in stimulating the rate of glucagon-like peptide-1 release from GLUTag enteroendocrine cells (threshold concentration 10 nM; 289% increase over basal rate at 1 MUM). Tigerinin peptides have potential for development into agents for the treatment of patients with type 2 diabetes. PMID- 27560387 TI - Home Mechanical Ventilation: An Overview. AB - Prevalence studies have shown heterogeneous use of home mechanical ventilation in different conditions, with a marked increase in uptake especially in users of noninvasive ventilation. Although randomized controlled trials have examined noninvasive ventilation in acute exacerbations of chronic obstructive pulmonary disease, for weaning from invasive ventilation and for postextubation respiratory failure, the evidence base for long-term noninvasive ventilation and comparisons with invasive ventilation are less well developed. The combination of noninvasive ventilation and cough-assist devices has reduced the indications for tracheotomy ventilation in some situations (e.g., Duchenne muscular dystrophy, spinal muscular atrophy, myopathies, and amyotrophic lateral sclerosis) and has also prolonged survival. Several excellent overviews have been written on the history of home mechanical ventilation and its evolution from negative pressure to positive pressure techniques, including a systematic review of outcomes. This review, instead, will cover recent trials, trends in the field, outcomes, and safety. Because the greatest growth has been in home noninvasive ventilation, this will be the main focus of this article. PMID- 27560388 TI - Macrophages as Active Nanocarriers for Targeted Early and Adjuvant Cancer Chemotherapy. AB - Taking advantage of the highly permeable vasculature and lack of lymphatic drainage in solid tumors (EPR effect), nanosized drug delivery systems or nanomedicines have been extensively explored for tumor-targeted drug delivery. However, in most clinical cases tumors such as the early stage tumors and post surgery microscopic residual tumors have not yet developed such pathological EPR features, i.e., EPR-deficient. Therefore, nanomedicines may not be applicable for such these tumors. Macrophages by nature can actively home and extravasate through the tight vascular wall into tumors and migrate to their hypoxic regions, and possess perfect stealth ability for long blood circulation and impressive phagocytosis for drug loadings. Thus, nanomedicines loaded in macrophages would harness both merits and gain the active tumor homing capability independent of the EPR effect for treatments of the EPR-deficient tumors. Herein, the critical considerations, current progress, challenges and future prospects of macrophages as carriers for nanomedicines are summarized, aiming at rational design of EPR independent tumor-targeting active nanomedicines for targeted early and adjuvant cancer chemotherapy. PMID- 27560389 TI - Chromosome sorting for the masses? PMID- 27560390 TI - Organic Micro/Nanoscale Lasers. AB - Micro/nanoscale lasers that can deliver intense coherent light signals at (sub)wavelength scale have recently captured broad research interest because of their potential applications ranging from on-chip information processing to high throughput sensing. Organic molecular materials are a promising kind of ideal platform to construct high-performance microlasers, mainly because of their superiority in abundant excited-state processes with large active cross sections for high gain emissions and flexibly assembled structures for high-quality microcavities. In recent years, ever-increasing efforts have been dedicated to developing such organic microlasers toward low threshold, multicolor output, broadband tunability, and easy integration. Therefore, it is increasingly important to summarize this research field and give deep insight into the structure-property relationships of organic microlasers to accelerate the future development. In this Account, we will review the recent advances in organic miniaturized lasers, with an emphasis on tunable laser performances based on the tailorable microcavity structures and controlled excited-state gain processes of organic materials toward integrated photonic applications. Organic pi-conjugated molecules with weak intermolecular interactions readily assemble into regular nanostructures that can serve as high-quality optical microcavities for the strong confinement of photons. On the basis of rational material design, a series of optical microcavities with different structures have been controllably synthesized. These microcavity nanostructures can be endowed with effective four level dynamic gain processes, such as excited-state intramolecular charge transfer, excited-state intramolecular proton transfer, and excimer processes, that exhibit large dipole optical transitions for strongly active gain behaviors. By tailoring these excited-state processes with molecular/crystal engineering and external stimuli, people have effectively modulated the performances of organic micro/nanolasers. Furthermore, by means of controlled assembly and tunable laser performances, efficient outcoupling of microlasers has been successfully achieved in various organic hybrid microstructures, showing considerable potential for the integrated photonic applications. This Account starts by presenting an overview of the research evolution of organic microlasers in terms of microcavity resonators and energy-level gain. Then a series of strategies to tailor the microcavity structures and excited-state dynamics of organic nanomaterials for the modulation of lasing performances are highlighted. In the following part, we introduce the construction and advanced photonic functionalities of organic microlaser-based hybrid structures and their applications in integrated nanophotonics. Finally, we provide our outlook on the current challenges as well as the future development of organic microlasers. It is anticipated that this Account will provide inspiration for the development of miniaturized lasers with desired performances by tailoring of excited-state processes and microcavity structures toward integrated photonic applications. PMID- 27560391 TI - A three steps approach for the reformation of medical CPD Systems: the Greek experience. PMID- 27560392 TI - Synergistic activity of Card11 mutant and Bcl6 in the development of diffuse large B-cell lymphoma in a mouse model. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma; it derives from germinal center B cells. Although DLBCL harbors many genetic alterations, synergistic roles between such alterations in the development of lymphoma are largely undefined. We previously established a mouse model of lymphoma by transplanting gene-transduced germinal center B cells into mice. Here, we chose one of the frequently mutated genes in DLBCL, Card11 mutant, to explore its possible synergy with other genes, using our lymphoma model. Given that BCL6 and BCL2 expression and/or function are often deregulated in human lymphoma, we examined the possible synergy between Card11, Bcl6, and Bcl2. Germinal center B cells were induced in vitro, transduced with Card11 mutant, Bcl6, and Bcl2, and transplanted. Mice rapidly developed lymphomas, with exogenously transduced Bcl2 being dispensable. Although some mice developed lymphoma in the absence of transduced Bcl6, the absence was compensated by elevated expression of endogenous Bcl6. Additionally, the synergy between Card11 mutant and Bcl6 in the development of lymphoma was confirmed by the fact that the combination of Card11 mutant and Bcl6 caused lymphoma or death significantly earlier and with higher penetrance than Card11 mutant or Bcl6 alone. Lymphoma cells expressed interferon regulatory factor 4 and PR domain 1, indicating their differentiation toward plasmablasts, which characterize activated B cell-like DLBCL that represents a clinically aggressive subtype in humans. Thus, our mouse model provides a versatile tool for studying the synergistic roles of altered genes underlying lymphoma development. PMID- 27560393 TI - Effect of the American Society of Clinical Oncology's Conflict of Interest Policy on Information Overload. PMID- 27560394 TI - The role of hypoxia in oral cancer and potentially malignant disorders: a review. AB - Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated 'potentially malignant disorders'. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia-induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena. PMID- 27560395 TI - QuickStats: Percentage of Adults Aged >=45 Years with Activity Limitations, by Age Group and Type of Limitation* - National Health Interview Survey,(?) United States, 2000-2015. AB - The percentage of adults aged 45-64 years with limitations in activities of daily living (ADLs) increased from 1.3% in 2000 to 2.0% in 2015, and the percentage with limitations in instrumental activities of daily living (IADLs) increased from 2.8% to 4.0%. Among adults aged >=65 years, the percentage with limitations in ADLs increased from 6.4% to 6.9%, and the percentage with limitations in IADLs decreased from 12.9% to 11.7%. PMID- 27560445 TI - Assessing Teratogenicity from the Clustering of Abnormal Phenotypes in Individual Zebrafish Larvae. AB - In previous publications, we described the population incidence of abnormalities in zebrafish larvae exposed to toxicants. Here, we examine the phenomenon of clustering or co-occurrence of abnormalities in individual larva. Our aim is to see how this clustering can be used to assess the specificity and severity of teratogenic effect. A total of 11,214 surviving larvae, exposed continuously from 1 day postfertilization (dpf) to one of 60 toxicants, were scored at 5 dpf for the presence of eight different abnormal phenotypes. These were as follows: pericardial edema, yolk sac edema, dispersed melanocytes, bent tail, bent trunk, hypoplasia of Meckel's cartilage, hypoplasia of branchial arches, and uninflated swim bladder. For 43/60 compounds tested, there was a concentration-dependent increase in the severity score (number of different abnormalities per larva). Statistical analysis showed that abnormalities tended to cluster (i.e., to occur in the same larva) more often than expected by chance alone. Yolk sac edema and dispersed melanocytes show a relatively strong association with one another and were typically the first abnormalities to appear in single larvae as the concentration of compound was increased. By contrast, hypoplastic branchial arches and hypoplastic Meckel's cartilage were only frequently observed in the most severely affected larvae. We developed a metric of teratogenicity (TC3/8), which represents the concentration of a compound that produces, on average, 3/8 abnormalities per larva. On this basis, the most teratogenic compounds tested here are amitriptyline, chlorpromazine hydrochloride, and sodium dodecyl sulfate; the least teratogenic is ethanol. We find a strong correlation between TC3/8 and LC50 of the 43 compounds that showed teratogenic effects. When we examined the ratio of TC3/8 to LC50, benserazide hydrochloride, copper (II) nitrate trihydrate, and nicotine had the highest specific teratogenicity, while aconitine, hesperidin, and ouabain octahydrate had the lowest. We conclude that analyzing the clustering of abnormalities per larva can provide an enriched teratogenic dataset compared with simple measurement of the population frequency of abnormalities. PMID- 27560446 TI - Mechanisms by which cocoa flavanols improve metabolic syndrome and related disorders. AB - Dietary administration of cocoa flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. These interactions likely occur primarily in the gastrointestinal tract, where native cocoa flavanol concentration is high. Flavanols may antagonize digestive enzymes and glucose transporters, causing a reduction in glucose excursion, which helps patients with metabolic disorders maintain glucose homeostasis. Unabsorbed flavanols, and ones that undergo enterohepatic recycling, will proceed to the colon where they can exert prebiotic effects on the gut microbiota. Interactions with the gut microbiota may improve gut barrier function, resulting in attenuated endotoxin absorption. Cocoa may also positively influence insulin signaling, possibly by relieving insulin-signaling pathways from oxidative stress and inflammation and/or via a heightened incretin response. The purpose of this review is to explore the mechanisms that underlie these outcomes, critically review the current body of literature related to those mechanisms, explore the implications of these mechanisms for therapeutic utility, and identify emerging or needed areas of research that could advance our understanding of the mechanisms of action and therapeutic potential of cocoa flavanols. PMID- 27560447 TI - Late postnatal shifts of parvalbumin and nitric oxide synthase expression within the GABAergic and glutamatergic phenotypes of inferior colliculus neurons. AB - The inferior colliculus (IC) is partitioned into three subdivisions: the dorsal and lateral cortices (DC and LC) and the central nucleus (ICC), and serves as an integration center of auditory information. Recent studies indicate that a certain population of IC neurons may represent the non-GABAergic phenotype, while they express well-established cortical/hippocampal GABAergic neuron markers. In this study we used the optical disector to investigate the phenotype of IC neurons expressing parvalbumin (PV) and/or nitric oxide synthase (NOS) in C57BL/6J mice during the late postnatal period. Four major types of IC neurons were defined by the presence (+) or absence (-) of PV, NOS, and glutamic acid decarboxylase 67 (GAD67): PV+ /NOS- /GAD67+ , PV+ /NOS+ /GAD67+ , PV+ /NOS- /GAD67- , and PV- /NOS+ /GAD67- . Fluorescent in situ hybridization for vesicular glutamate transporter 2 mRNA indicated that almost all GAD67- IC neurons represented the glutamatergic phenotype. The numerical densities (NDs) of total GAD67+ IC neurons remained unchanged in all subdivisions. The NDs of PV+ /NOS- /GAD67+ neurons and PV- /NOS+ /GAD67- neurons were reduced with age in the ICC, while they remained unchanged in the DC and LC. By contrast, the NDs of PV+ /NOS+ /GAD67+ neurons and PV+ /NOS- /GAD67- neurons were increased with age in the ICC, although there were no changes in the DC and LC. The cell body size of GAD67+ IC neurons did not vary according to the expression of PV with or without NOS. The present findings indicate that the expression of PV and NOS may shift with age within the GABAergic and glutamatergic phenotypes of IC neurons during the late postnatal period. J. Comp. Neurol. 525:868-884, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27560449 TI - Errors Reported in Percentage Differences, 95% CIs, and Associated P Values. PMID- 27560448 TI - First line treatment with newer tyrosine kinase inhibitors in chronic myeloid leukemia associated with deep and durable molecular response - systematic review and meta-analysis. AB - BACKGROUND: The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We published a meta-analysis examining the role of newer TKIs as first line treatment in chronic phase CML. In view of the recently published data, we decided to update it. METHODS: We conducted a systematic review and meta analysis of randomized controlled trials comparing first line treatment with imatinib to the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib). We searched MEDLINE, conference proceedings and databases of ongoing trials up to August 2015. RESULTS: Our search yielded eight trials including 3554 patients. Treatment with the newer TKIs significantly improved major molecular response (MMR) at all time points and increased the rate of complete molecular response (CMR) at 12 and 24 months [relative risk (RR) 2.58, 95% CI 1.98-3.37, six trials and RR 2.05, 95% CI 1.63-2.58, three trials, respectively]. Early molecular response at three months was better with the newer TKIs (RR 1.33, 95% CI 1.26 1.40, six trials). Importantly, progression rate to accelerated or blastic phase was significantly lower with the newer TKIs at 12, 24 months and 5 years. Yet, there was no difference in all-cause mortality. The risk of adverse events requiring treatment discontinuation increased with the newer TKIs. CONCLUSIONS: With a longer follow-up, the newer TKIs remain more potent than imatinib, yet with no significant effect on survival. As CMR is a prerequisite for treatment discontinuation and cure, the newer TKIs favor treatment cessation. PMID- 27560452 TI - Highly Selective Deoxydehydration of Tartaric Acid over Supported and Unsupported Rhenium Catalysts with Modified Acidities. AB - The deoxydehydration (DODH) of sugar acids to industrially important carboxylic acids is a very attractive topic. Oxorhenium complexes are the most-often employed DODH catalysts. Because of the acidity of the rhenium catalysts, the DODH products of sugar acids were usually in the form of mixture of free carboxylic acids and esters. Herein, we demonstrate strategies for the selective DODH of sugar acids to free carboxylic acids by tuning the Lewis acidity or the Bronsted acidity of the rhenium-based catalysts. Starting from tartaric acid, up to 97 % yield of free maleic acid was achieved. Based on our strategies, functional polymer immobilized heterogeneous rhenium catalysts were also developed for the selective DODH conversion of sugar acids. PMID- 27560450 TI - The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic proteins. AB - The N-terminal amino acid of a protein is an essential determinant of ubiquitination and subsequent proteasomal degradation in the N-end rule pathway. Using para-chloroamphetamine (PCA), a specific inhibitor of the arginylation branch of the pathway (Arg/N-end rule pathway), we identified that blocking the Arg/N-end rule pathway significantly impaired the fusion of autophagosomes with lysosomes. Under ER stress, ATE1-encoded Arg-tRNA-protein transferases carry out the N-terminal arginylation of the ER heat shock protein HSPA5 that initially targets cargo proteins, along with SQSTM1, to the autophagosome. At the late stage of autophagy, however, proteasomal degradation of arginylated HSPA5 might function as a critical checkpoint for the proper progression of autophagic flux in the cells. Consistently, the inhibition of the Arg/N-end rule pathway with PCA significantly elevated levels of MAPT and huntingtin aggregates, accompanied by increased numbers of LC3 and SQSTM1 puncta. Cells treated with the Arg/N-end rule inhibitor became more sensitized to proteotoxic stress-induced cytotoxicity. SILAC-based quantitative proteomics also revealed that PCA significantly alters various biological pathways, including cellular responses to stress, nutrient, and DNA damage, which are also closely involved in modulation of autophagic responses. Thus, our results indicate that the Arg/N-end rule pathway may function to actively protect cells from detrimental effects of cellular stresses, including proteotoxic protein accumulation, by positively regulating autophagic flux. PMID- 27560451 TI - First Report of Babesia microti-Caused Babesiosis in Spain. AB - Babesiosis is an emerging zoonosis now found in several areas of the world. Using PCR and indirect immunofluorescence assay, we have diagnosed the first case of human babesiosis caused by Babesia microti in Spain. Diagnosis was delayed because of the nonspecific clinical symptoms that occurred in an immunocompetent patient. PMID- 27560453 TI - Enabling Efficient and Confident Annotation of LC-MS Metabolomics Data through MS1 Spectrum and Time Prediction. AB - Liquid chromatography coupled to electrospray ionization-mass spectrometry (LC ESI-MS) is a versatile and robust platform for metabolomic analysis. However, while ESI is a soft ionization technique, in-source phenomena including multimerization, nonproton cation adduction, and in-source fragmentation complicate interpretation of MS data. Here, we report chromatographic and mass spectrometric behavior of 904 authentic standards collected under conditions identical to a typical nontargeted profiling experiment. The data illustrate that the often high level of complexity in MS spectra is likely to result in misinterpretation during the annotation phase of the experiment and a large overestimation of the number of compounds detected. However, our analysis of this MS spectral library data indicates that in-source phenomena are not random but depend at least in part on chemical structure. These nonrandom patterns enabled predictions to be made as to which in-source signals are likely to be observed for a given compound. Using the authentic standard spectra as a training set, we modeled the in-source phenomena for all compounds in the Human Metabolome Database to generate a theoretical in-source spectrum and retention time library. A novel spectral similarity matching platform was developed to facilitate efficient spectral searching for nontargeted profiling applications. Taken together, this collection of experimental spectral data, predictive modeling, and informatic tools enables more efficient, reliable, and transparent metabolite annotation. PMID- 27560454 TI - A mixed methods study of peer-to-peer support in a group-based lifestyle intervention for adults with serious mental illness. AB - OBJECTIVE: There is potential for peer support to enhance healthy lifestyle interventions targeting changes in body weight and fitness for adults with serious mental illness. The purpose of this study was to explore peer-to-peer support among individuals participating in a group lifestyle intervention that included social media to enhance in-person weight management sessions. METHOD: A mixed methods study design was used to explore participants' perceptions and experiences of support from other group members during a 6-month group lifestyle intervention. Twenty-five individuals with serious mental illness reported their perceptions of the peer group environment and social support during the intervention. Seventeen of these individuals also participated in focus group interviews further exploring their experiences with group members. RESULTS: More than 80% of participants agreed that other group members were trustworthy and dependable, and 92% reported a high level of shared purpose and active participation in the group. Participants described how shared learning and group problem-solving activities fostered friendships and provided essential support for health behavior change. Sharing information, personal successes and challenges, and "being in the same boat" as other group members were key features of peer-to-peer support. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings from this exploratory study suggest that participants enrolled in a group-based lifestyle intervention for people with serious mental illness experience peer-to peer support in various ways that promote health behavior change. These findings highlight opportunities to enhance future lifestyle interventions with collaborative learning and social network technologies that foster peer support among participants. (PsycINFO Database Record PMID- 27560455 TI - Pupillometer-based neurofeedback cognitive training to improve processing speed and social functioning in individuals at clinical high risk for psychosis. AB - OBJECTIVE: Among individuals at clinical high risk (CHR) for psychosis, processing speed (PS) has been related to social and role functioning regardless of conversion to schizophrenia. This information processing dysfunction is a gateway to broader behavioral deficits such as difficulty executing social behaviors. We examined the feasibility of improving information processing relevant to social situations in CHR, including its sustainability at 2-month follow-up, and its association with concurrent social function. METHOD: This was a double-blind RCT in which 62 CHR participants were randomized to Processing Speed Training (PST) or an active control matched for training format and the same dose and duration of treatment. PST is a tablet-based program that uses pupillometry-based neurofeedback to continually adjust training parameters for an optimal neurocognitive load and to improve visual scanning efficiency by inhibiting selection of nonessential targets and discriminating figure-ground details. RESULTS: The PST group showed faster motoric and nonmotoric PS at post training and 2-month follow-up. At 2 month follow-up, the PST group reported better overall social adjustment. Changes in PS from baseline to 2 months were correlated with overall social adjustment and social avoidance in the entire sample. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This is the first study to test focal neurofeedback-based cognitive training for PS deficits in the putatively prodromal phase of schizophrenia to address associated social morbidity. Targeting PS appears to be a promising pathway to decreasing comorbidity and mitigating a risk factor for psychosis. (PsycINFO Database Record PMID- 27560457 TI - Single Component Lanthanide Hybrids Based on Metal-Organic Framework for Near Ultraviolet White Light LED. AB - Near-UV single-phase white-light phosphor (Eu0.045Tb0.955CPOMBA/La0.6Eu0.1Tb0.3CPOMBA) based on metal-organic framework was prepared by in situ doping isostructural lanthanide MOF with Eu(3+) and Tb(3+), and it is found that the energy can effectively transfer from organic ligand to lanthanides, which can overcome weak absorption under direct excitation of lanthanide ions due to the forbidden f-f transitions. The photoluminescence and thermostability of the new MOF phosphor are investigated, and effective white light emission is achieved under 365 and 380 nm excitations. By employing Eu0.045Tb0.955CPOMBA as phosphor, we fabricated a near-ultraviolet white-light emitting diode (n-UV WLED) (365 nm) with low CCT (5733 K), high CRI (Ra = 73.4), and CIE chromaticity coordinate (0.3264, 0.3427). This approach may open new perspectives for developing single-phase UV phosphors. PMID- 27560456 TI - A single-dose study investigating the pharmacokinetics and pharmacodynamics of edoxaban at 30-90 mg in healthy Chinese volunteers. AB - 1. This study investigated the pharmacokinetics and pharmacodynamics of single dose edoxaban in healthy Chinese subjects. 2. This single-centre, open-label, 3 occasion, cross-over study enrolled six males and six females. Subjects received a single-oral-dose of edoxaban 30-90 mg in each study occasion under fasting condition. Serial blood samples were collected to measure the plasma concentrations of edoxaban and its major active metabolite D21-2393. Meanwhile, PT, INR, aPTT were measured pre- and post-dose. Safety was assessed. 3. After administration, edoxaban was rapidly absorbed (median Tmax = 1-2 h). With rapid transformation, peak concentration of D21-2393 was reached within 2-h post-dose. The elimination half-life of edoxaban was 5-20 h. The dose-exposure relationships were slightly lower-than-dose-proportional for both edoxaban and D21-2393. Although women had higher plasma exposure of edoxaban and D21-2393 than men, it was considered clinically insignificant. 4. The effects of edoxaban on all pharmacodynamic biomarkers were concentration-dependent and linearly-correlated to plasma level of the compound. Minor bleeding was the most commonly reported adverse events. 5. Single oral doses of edoxaban 30-90 mg were safe and well tolerated in healthy Chinese volunteers. 6. The pharmacokinetic and pharmacodynamic profiles of edoxaban in Chinese subjects were comparable to those observed in Caucasian and Japanese populations. PMID- 27560458 TI - Cardamonin Alleviates Pressure Overload-induced Cardiac Remodeling and Dysfunction Through Inhibition of Oxidative Stress. AB - Pressure overload-induced cardiac remodeling and dysfunction progress to heart failure, which is mainly due to excessive oxidative stress. Hence, our study aimed to illustrate whether cardamonin, a kind of chalcone, could attenuate maladaptive cardiac changes and ameliorate cardiac insufficiency through its antioxidant mechanism. In vivo, our study revealed that cardamonin treatment could attenuate transverse aortic contraction-induced cardiac remodeling and dysfunction. Histological observations have suggested that cardamonin inhibited the occurrence of excessive cardiac oxidative stress and apoptosis. In vitro, we found that 3 treatments with angiotensin II (Ang II), hydrogen peroxide, and Nox4 overexpression in H9C2 cells markedly augmented intracellular oxidative stress as measured by superoxide dismutase, L-glutathione, and malonaldehyde. Conversely, cardamonin treatment notably alleviated oxidative stress induced by the 3 above mentioned treatments. Furthermore, all 3 treatments resulted in increased apoptotic cell death, whereas cardamonin treatment reduced apoptosis in H9C2 cells. Moreover, cardamonin significantly abrogated the expression of Bax, apoptosis inducing factor, cytochrome c, and caspase-3 and caspase-9 and enhanced the expression of Bcl-2 and Bcl-xl. In conclusion, these findings provide a new possibility for cardamonin to alleviate pressure overload-induced heart failure. PMID- 27560459 TI - Single-Molecule-Magnet Behavior and Fluorescence Properties of 8 Hydroxyquinolinate Derivative-Based Rare-Earth Complexes. AB - Five tetranuclear rare-earth complexes, [RE4(dbm)4L6(MU3-OH)2] [HL = 5- (4 fluorobenzylidene)-8-hydroxylquinoline; dbm = 1,3-diphenyl-1,3-propanedione; RE = Y (1), Eu (2), Tb (3), Dy (4), Lu (5)], have been synthesized and completely characterized. The X-ray structural analyses show that each [RE4] complex is of typical butterfly or rhombus topology. Each RE(III) center exists in an eight coordinated square-antiprism environment. Magnetic studies reveal that complex 4 displays single-molecule-magnet behavior below 10 K under a zero direct-current field, with an effective anisotropy barrier (DeltaE/kB = 56 K). The fluorescence properties of complexes 1-5 were also investigated. Complexes 2-4 showed their characteristic peaks for the corresponding RE(III) center, while complexes 1 and 5 showed the same emission peaks with the ligand when they were excited at the same wavelength. PMID- 27560460 TI - Decarbonylative Silylation of Esters by Combined Nickel and Copper Catalysis for the Synthesis of Arylsilanes and Heteroarylsilanes. AB - An efficient nickel/copper-catalyzed decarbonylative silylation reaction of carboxylic acid esters with silylboranes is described. This reaction provides access to structurally diverse silanes with high efficiency and excellent functional-group tolerance starting from readily available esters. PMID- 27560461 TI - Copper-Catalyzed Three-Component Tandem Cyclization for One-Pot Synthesis of 1,4 Benzothiazines. AB - A copper-catalyzed three-component tandem reaction has been developed for the convenient and practical synthesis of 1,4-benzothiazines. A variety of terminal alkynes and 2-iodo/bromophenyl isothiocyanates underwent this one-pot cyclization with aqueous ammonia to afford 1,4-benzothiazines in moderate to good yields. PMID- 27560462 TI - Hydrogen Peroxide Coordination to Cobalt(II) Facilitated by Second-Sphere Hydrogen Bonding. AB - M(H2 O2 ) adducts have been postulated as intermediates in biological and industrial processes; however, only one observable M(H2 O2 ) adduct has been reported, where M is redox-inactive zinc. Herein, direct solution-phase detection of an M(H2 O2 ) adduct with a redox-active metal, cobalt(II), is described. This Co(II) (H2 O2 ) compound is made observable by incorporating second-sphere hydrogen-bonding interactions between bound H2 O2 and the supporting ligand, a trianionic trisulfonamido ligand. Thermodynamics of H2 O2 binding and decay kinetics of the Co(II) (H2 O2 ) species are described, as well as the reaction of this Co(II) (H2 O2 ) species with Group 2 cations. PMID- 27560463 TI - Juvenile growth reduces the influence of epithelial sodium channels on myogenic tone in skeletal muscle arterioles. AB - Previous studies have documented that rapid juvenile growth is accompanied by functional changes in the arteriolar endothelium, but much less is known about functional changes in arteriolar smooth muscle over this period. In this study, we investigate the possible contribution of epithelial sodium channels (ENaC) to the myogenic behaviour of arterioles at two stages of juvenile growth. The effects of the ENaC inhibitor benzamil on different levels of myogenic tone were studied in isolated gracilis muscle arterioles from rats aged 21-28 days ("weanlings") and 42-49 days ("juveniles"). ENaC subunit expression in the arteriolar wall was also determined, and the interaction between ENaC and nitric oxide (NO) in regulating vascular tone was explored by combined use of benzamil and NG -monomethyl-l-arginine (l-NMMA). At physiological pressures, both steady state myogenic tone and the dynamic adjustments in this tone triggered by acute pressure changes were less in juvenile arterioles than in weanling arterioles. alpha, beta and gamma ENaC protein was present in arterioles at both ages, but benzamil only had an effect on myogenic tone in weanling arterioles. In these vessels, benzamil increased, rather than decreased, myogenic tone, and this effect was prevented by l-NMMA or endothelial removal. These findings suggest that although ENaC is present in gracilis muscle arterioles of both weanling and juvenile rats, it is not obligatory for the genesis of myogenic activity in these vessels at either age. However, ENaC activity can significantly modulate the level of myogenic tone through stimulation of endothelial NO release at an early stage of growth. PMID- 27560464 TI - Association between Participation in an Intensive Longitudinal Assessment Program and Performance on a Cognitive Examination in the Maintenance of Certification in Anesthesiology Program(r). AB - BACKGROUND: As part of the Maintenance of Certification in Anesthesiology Program(r) (MOCA(r)), the American Board of Anesthesiology (Raleigh, North Carolina) developed the MOCA Minute program, a web-based intensive longitudinal assessment involving weekly questions with immediate feedback and links to learning resources. This observational study tested the hypothesis that individuals who participate in the MOCA Minute program perform better on the MOCA Cognitive Examination (CE) compared with those who do not participate. METHODS: Two separate cohorts of individuals eligible for July 2014 and January 2015 CEs were invited to participate in this pilot. The CE scores for each cohort were compared between those who did and did not participate, controlling for the factors known to affect performance. For the first cohort, examination performances for topics covered and not covered by the MOCA Minute were analyzed separately. RESULTS: Six hundred sixteen diplomates in July 2014 and 684 diplomates in January 2015 took the CE for the first time. In multiple regression analysis, those actively participating scored 9.9 points (95% CI, 0.8 to 18.9) and 9.3 points (95% CI, 2.3 to 16.3) higher when compared with those not enrolled, respectively. Compared to the group that did not enroll in MOCA Minute, those who enrolled but did not actively participate demonstrated no improvement in scores. MOCA Minute participation was associated with improvement in both questions covering topics included the MOCA Minute and questions not covering these topics. CONCLUSIONS: This analysis provides evidence that voluntary active participation in a program featuring frequent knowledge assessments accompanied by targeted learning resources is associated with improved performance on a high stakes CE. PMID- 27560465 TI - Commentary on the Potential of the MOCA Minute Program(r). PMID- 27560466 TI - Vagus Nerve Attenuates Hepatocyte Apoptosis upon Ischemia-Reperfusion via alpha7 Nicotinic Acetylcholine Receptor on Kupffer Cells in Mice. AB - BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a complication of liver surgery. As much as 50% of hepatocytes undergo apoptosis within the first 24 h of reperfusion. The neurotransmitters of the vagus nerve can activate alpha7 nicotinic acetylcholine receptor (alpha7nAChR) on macrophages. The function of Kupffer cells (KCs) determines HIR injury. We hypothesize that the vagus nerve could attenuate HIR-induced hepatocyte apoptosis by activating alpha7nAChR on KCs. METHODS: Hepatic vagotomized C57BL/6J mice, KC-eliminated C57BL/6J mice, and alpha7nAChR mice were used for HIR. Primary KCs and hepatocytes were subjected to hypoxia/reoxygenation (HR). Liver injury, hepatocyte apoptosis, reactive oxygen species (ROS) production, and soluble CD163 were measured. RESULTS: Hepatic vagotomy and alpha7nAChR caused higher levels of alanine transaminase and liver caspase-3 and -8 activity by HIR. Activating alpha7nAChR attenuated these changes in wild-type but not in the alpha7nAChR mice. Furthermore, activating alpha7nAChR diminished hepatic injury and reduced liver apoptosis by HIR in vagotomized mice. In vitro, activating alpha7nAChR reduced apoptosis of hepatocytes cocultured with KCs that suffered HR. Similar to the effects by catalase, activating alpha7nAChR on KCs reduced ROS and H2O2 by HR. The supernatant from KCs, with alpha7nAChR activated or catalase treated, prevented hepatocyte apoptosis by HR. Finally, KC elimination reduced HIR-induced H2O2 production in mice. Activating alpha7nAChR significantly attenuated soluble CD163 both in mice by HIR (serum: 240 +/- 34 vs. 446 +/- 72; mean +/- SD; n = 8; P < 0.01) and in KCs by HR (supernatant: 4.23 +/- 0.06 vs. 5.60 +/- 0.18; n = 3; P < 0.01). CONCLUSIONS: The vagus nerve could minimize HIR-induced liver apoptosis through activating alpha7nAChR on KCs possibly by preventing their excessive ROS production. PMID- 27560467 TI - microRNA profiling in atherosclerosis, diabetes, and migraine. AB - microRNAs (miRNAs) are a broad group of endogenous small non-coding molecules that reduce the transcription of mRNA and play a key role in post-transcriptional gene processes. miRNAs are involved in onset and progression of several human disorders such as infectious and immune non-infectious diseases, cancers, metabolic and cardiovascular disorders. They regulate the expression of gene targets (e.g. oncogenes and tumor suppressor genes) and act as gene repressors with mRNA binding and cleavage. The increasing evidence that miRNAs play a key role in the pathogenesis of cardiovascular conditions could radically change the future management approach to these disorders. This review focuses on current knowledge about the influence of miRNAs on cardiovascular disease, with particular regard to common conditions such as atherosclerosis, diabetes and migraine. Key messages miRNAs are a group of endogenous small non-coding RNA segments measuring 19-25 nucleotides that are involved in physiologic processes and onset and progression of disorders such as infectious and immune non infectious diseases, cancers, metabolic and cardiovascular disorders. miRNAs expression guarantees vascular integrity, by regulating apoptosis, VEGF pathway and VCAM 1 expression (-126), and is involved in atherosclerotic plaque formation process and progression. Hyperglycemia, overt diabetes, and their complications are associated with overexpression of several miRNAs. An altered expression of miRNAs has also been postulated in migraine patients, although only a few preliminary studies have so far been performed with this respect. PMID- 27560468 TI - Clinical Experience With the Use of Negative Pressure Wound Therapy Combined With a Silver-impregnated Dressing in Mixed Wounds: A Retrospective Study of 50 Cases. AB - Although negative pressure wound therapy (NPWT) has been used for more than 20 years, as far as the authors are aware, there is little research aimed at the evaluation of the combination of NPWT with a silver-impregnated dressing. OBJECTIVE: The aim of this study was to examine the effect, efficacy, and safety of NPWT in conjunction with a silver-impregnated dressing. MATERIALS AND METHODS: The authors used a retrospective study of 54 acute and chronic wounds treated in 50 patients over a 2-year period. Demographic data, wound characterizations, wound cultures before and after NPWT, the duration of NPWT and number of sponge changes for each patient, the types of surgical procedures used for wound closure following NPWT, and the healing time and length of hospital stays were recorded. RESULTS: In 26 wounds, deep structures (ie, bones and tendons) were exposed. The mean NPWT duration was 9.2 days. Mean healing time was 16 days. There was a statistically significant decrease in the pathogenic microbial strains after NPWT treatment combined with the silver-impregnated dressing (paired t test; P = 0.0038). The shift from complicated to easier surgical wound-closure procedures was observed. DISCUSSION: According to all results obtained, described, and discussed, the authors consider the use of a nonadherent silver-impregnated dressing in conjunction with NPWT to be beneficial and efficacious. No adverse events or reactions related to the silver-impregnated contact layer used during NPWT have been observed in the patients, which confirmed the safety of this method. PMID- 27560469 TI - The Presence of Oxygen in Wound Healing. AB - Oxygen must be tightly governed in all phases of wound healing to produce viable granulation tissue. This idea of tight regulation has yet to be disputed; however, the role of oxygen at the cellular and molecular levels still is not fully understood as it pertains to its place in healing wounds. In an attempt to better understand the dynamics of oxygen on living tissue and its potential role as a therapy in wound healing, a substantial literature review of the role of oxygen in wound healing was performed and the following key points were extrapolated: 1) During energy metabolism, oxygen is needed for mitochondrial cytochrome oxidase as it produces high-energy phosphates that are needed for many cellular functions, 2) oxygen is also involved in the hydroxylation of proline and lysine into procollagen, which leads to collagen maturation, 3) in angiogenesis, hypoxia is required to start the process of wound healing, but it has been shown that if oxygen is administered it can accelerate and sustain vessel growth, 4) the antimicrobial action of oxygen occurs when nicotinamide adenine dinucleotide phosphate (NADPH)-linked oxygenase acts as a catalyst for the production of reactive oxygen species (ROS), a superoxide ion which kills bacteria, and 5) the level of evidence is moderate for the use of hyperbaric oxygen therapy (HBOT) for diabetic foot ulcers, crush injuries, and soft-tissue infections. The authors hypothesized that HBOT would be beneficial to arterial insufficiency wounds and other ailments, but at this time further study is needed before HBOT would be indicated. PMID- 27560470 TI - Comparison Between Tc-99m WBC SPECT/CT and MRI for the Diagnosis of Biopsy-proven Diabetic Foot Osteomyelitis. AB - OBJECTIVE: Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO), with a reported accuracy of 79%. The gold standard to diagnose osteomyelitis is bone biopsy, with a positive culture and/or histopathology findings consistent with osteomyelitis. The purposes of this study are to assess the accuracy of technetium-99m (Tc-99m) labeled white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging for diagnosing DFO confirmed by bone biopsy and to compare that to the diagnostic accuracy of an MRI. MATERIALS AND METHODS: The authors performed a retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large municipal hospital between 2010 and 2013. Patients were selected on the basis of whether they received an MRI or a SPECT/CT. Patients whose scans were not within a clinically relevant time frame of the biopsy were excluded. Imaging results were correlated with probability of osteomyelitis determined by bone biopsy. RESULTS: For inclusion criteria, 110 patients met the study's criteria: 52 SPECT/CT patients and 58 MRI patients. The sensitivity, specificity, positive predictive value, and negative predictive value of SPECT/CT were 89%, 35%, 74%, and 60%, respectively; the corresponding values for MRI were 87%, 37%, 74%, and 58%, respectively. There were no significant differences in accuracy of diagnosing DFO between imaging techniques. CONCLUSION: This data suggests that the diagnostic accuracy of SPECT/CT imaging in DFOs is similar to an MRI. PMID- 27560471 TI - Effect of Asiaticoside, Collagenase, and Alpha-chymotrypsin on Wound Healing in Rabbits. AB - Wound dressing materials such as asiaticoside, collagenase, and alpha chymotrypsin are often used for effective wound healing activity. OBJECTIVES: In this study, the effects of asiaticoside, collagenase, and alpha-chymotrypsin were studied in rabbit models with open wounds with tissue loss and with full thickness flank excisions for a period of 21 days. MATERIALS AND METHODS: Three groups of 4 rabbits were examined during trial periods of 7, 14, and 21 days. Four circular wounds measuring 1.5 cm in diameter were made on the dorsal sides of the animals: 2 on the right and 2 the left. Asiaticoside, collagenase, and alpha-chymotrypsin were applied to wounds daily for a period of 7, 14, and 21 days, while 1 gauzed wound served as the control. All biopsy specimens were histopathologically evaluated for recovery. On day 7, microscopic review showed no differences in wound healing between groups. RESULTS: By day 14, alpha chymotrypsin showed the quickest reepithelialization (P < 0.05); and by day 21 asiaticoside and collagenase (P < 0.01) showed effective recovery, due to the completion of wound healing for all animals in both groups. CONCLUSION: Alpha chymotrypsin is more effective than the other 2 groups for only 14 days. The effectiveness of asiaticoside and collagenase displayed a more rapid improvement in comparison to alpha-chymotrypsin for healing open wounds with tissue loss for a period of 21 days. PMID- 27560472 TI - The Incidence of Confounding Factors in Patients With Diabetes Mellitus Hospitalized for Diabetic Foot Ulcers. AB - INTRODUCTION: Uncontrolled deformity, deep infection, and/or ischemia-hypoxia are highly associated with healing challenges of diabetic foot ulcers (DFUs). This paper reports the occurrences of these factors that the authors label the "Troublesome Triad" (TT) in a prospective series of 62 patients with diabetes mellitus (DM), who were hospitalized because of their DFUs. MATERIALS AND METHODS: With Institutional Review Board approval, the authors gathered data in a prospective series of patients hospitalized because of lower extremity wounds. From this data, they analyzed the DFU cohort for the incidence of each of the components of the TT. The severity of the wound was graded with the authors' 0 to 10 Wound Score in the patients who had components of the TT and compared with those who did not. RESULTS: One or more components of the TT were observed in 57 patients (91.9%). As the number of confounders increased, mean Wound Scores decreased from 5.2 for 1 confounder to 2.9 for 3 confounders (P = 0.003). Most patients had 1 or 2 confounders (38.7% and 45.2%, respectively), while only 5 (8.1%) patients had all 3 confounders. Unresolved infection was the major confounder in 38 (61.3%) patients, uncontrolled deformity in 31 (50.0%), and ischemia-hypoxia in 26 (41.9%). CONCLUSION: For those patients with DM who were hospitalized because of DFUs, confounders that require remedial interventions were present in more than 90% of patients. Recognition and management of the TT eliminates wasteful uses of resources in an attempt to heal lower extremity wounds in patients with DM where the confounders need to be addressed first. PMID- 27560473 TI - Evidence Corner: Controversy Surrounding Wound-edge Protectors. PMID- 27560474 TI - Editorial Message: Embracing Change. PMID- 27560475 TI - Letter to The Editor: Femoral Vein Cannulation in the Treatment of Osteomyelitis. PMID- 27560476 TI - Cutaneous Tuberculosis Occurring After a Skin Cut in a Child. AB - BACKGROUND: Tuberculosis is a common problem in Turkey, and cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis. Herein, the authors describe a case of cutaneous tuberculosis (lupus vulgaris) occurring after contact with a sheep. CASE: A 15-year-old boy was admitted to Marmara University School of Medicine Pendik Training and Research Hospital (Istanbul, Turkey) with delayed wound healing on the left index finger and left axillary lymphadenopathy. His medical history was unremarkable except for a wound incurred when he slaughtered a sheep 3 months before. One month after this injury, the patient developed enlargement of the left axillary lymph node on the side of the wounded extremity, and the wound turned a dark black color. The biopsy specimens obtained from the wounded skin and lymph nodes showed granulomatous reaction, but acid fast bacilli (AFB) could not be shown with Ehrlich-Ziehl Neelsen staining. The patient tested positive in an interferon-gamma release assay. Computerized tomography scans of the thorax were normal, and early morning gastric lavage specimen was negative for AFB. The wound and axillary lymphadenopathy disappeared after institution of anti-tuberculosis therapy. CONCLUSION: Tuberculosis infection must be considered in chronic skin lesions with granulomatous reaction occurring in countries with high prevalence of tuberculosis. PMID- 27560477 TI - The Anion Effect on Li(+) Ion Coordination Structure in Ethylene Carbonate Solutions. AB - Rechargeable lithium ion batteries are an attractive alternative power source for a wide variety of applications. To optimize their performances, a complete description of the solvation properties of the ion in the electrolyte is crucial. A comprehensive understanding at the nanoscale of the solvation structure of lithium ions in nonaqueous carbonate electrolytes is, however, still unclear. We have measured by femtosecond vibrational spectroscopy the orientational correlation time of the CO stretching mode of Li(+)-bound and Li(+)-unbound ethylene carbonate molecules, in LiBF4, LiPF6, and LiClO4 ethylene carbonate solutions with different concentrations. Surprisingly, we have found that the coordination number of ethylene carbonate in the first solvation shell of Li(+) is only two, in all solutions with concentrations higher than 0.5 M. Density functional theory calculations indicate that the presence of anions in the first coordination shell modifies the generally accepted tetrahedral structure of the complex, allowing only two EC molecules to coordinate to Li(+) directly. Our results demonstrate for the first time, to the best of our knowledge, the anion influence on the overall structure of the first solvation shell of the Li(+) ion. The formation of such a cation/solvent/anion complex provides a rational explanation for the ionic conductivity drop of lithium/carbonate electrolyte solutions at high concentrations. PMID- 27560479 TI - Cytotoxicity and biodistribution studies of luminescent Au(i) and Ag(i) N heterocyclic carbenes. Searching for new biological targets. AB - A range of fluorescent and biologically compatible gold(i)-N-heterocyclic carbenes bearing acridine as a wingtip group and either a 2-mercaptopyridine or a tetra-O-acetyl-1-thio-beta-d-glucopyranoside as an ancillary ligand has been synthesised. Their luminescence, cytotoxicity and biodistribution have been investigated together with those of analogous gold(i) and silver(i) chloride- and bis-NHC complexes. All complexes displayed emissions based on IL transitions centred on the acridine moiety. The cytotoxic activity measured in lung, A549, and pancreatic, MiaPaca2, carcinoma cell lines revealed a general cytotoxicity pattern (thiolate > biscarbene > chloride derivatives) and flow cytometry assays pointed towards apoptosis as the cell death mechanism. Moreover, fluorescence cell microscopy disclosed an unusual biodistribution behavior, being mainly localised in lysosomes and to a lesser extent in the nucleus. Preliminary DNA interaction experiments suggested the metal fragment and not the acridine moiety as responsible for such biodistribution, which widen the scope for new biological targets. PMID- 27560478 TI - Comparison of Melatonin, Hypertonic Saline, and Hydroxyethyl Starch for Resuscitation of Secondary Intra-Abdominal Hypertension in an Animal Model. AB - A variety of agents may have a beneficial effect in reducing injury-induced intestinal edema of fluid, but studies confirming the efficacy and mechanisms of these agents in secondary intra-abdominal hypertension (IAH) are lacking. This study was to compare the effectiveness of melatonin, 7.5% hypertonic saline (HS), and hydroxyethyl starch 130/0.4 (HES) on the resuscitation of secondary IAH in a rat model. Female SD rats were divided into: sham group, shock group, lactated Ringer solution (LR) group, melatonin group, HS group, and HES group. Except for the sham group, all rats underwent a combination of inducing portal hypertension, hemorrhaging to a MAP of 40 mmHg for 2 hr, and using an abdominal restraint device. The collected blood was reinfused and the rats were treated with LR (30ml/h), melatonin (50 mg/kg) + LR, HS (6 ml/kg) + LR, and HES (30 ml/kg) + LR, respectively. The shock group received no fluids. LR was continuously infused for 6hr. The intestinal permeability, immunofluorescence of tight junction proteins, transmission electron microscopy, level of inflammatory mediators (TNF-a, IL 1beta, IL-6) and of biochemical markers of oxidative stress (malondialdehyde, myeloperoxidase activity, and glutathione peroxidase) were assessed. Expressions of the protein kinase B (Akt) and of tight junction proteins were detected by Western blot. Compared with LR, HS, and HES, melatonin was associated with less inflammatory and oxidative injury, less intestinal permeability and injury, and lower incidence of secondary IAH in this model. The salutary effect of melatonin in this model was associated with the upregulation of intestinal Akt phosphorylation. PMID- 27560481 TI - Opportunities and technical challenges in next-generation sequencing for diagnosis of rare pediatric diseases. AB - INTRODUCTION: Rare pediatric diseases are clinically severe with high rates of mortality and morbidity. This paper outlines how next-generation sequencing (NGS) can be used to greatly advance identification of the underlying genetic causes. Areas covered: This manuscript is a blend of evidence obtained from literature searches from PubMed and rare disease related websites, laboratory experience and the author's opinions. The paper covers the current state of the field and identifies where the challenges lie and how they are being overcome, using up-to date references. Expert commentary: The field of NGS is still relatively new but it has already transformed the field of rare disease research. Technological advances in instrumentation, computational hardware and software have resulted in the identification of many causative genes, but as sequencing moves into population-scale initiatives standardisation and data sharing is going to be of paramount importance to ensure we derive the maximum benefit for patients. PMID- 27560480 TI - TNFalpha Augments Cytokine-Induced NK Cell IFNgamma Production through TNFR2. AB - NK cells play a central role in innate immunity, acting directly through cell mediated cytotoxicity and by secreting cytokines. TNFalpha activation of TNFR2 enhances NK cell cytotoxicity, but its effects on the other essential function of NK cells - cytokine production, for which IFNgamma is paramount - are poorly defined. We identify the expression of both TNFalpha receptors on human peripheral blood NK cells (TNFR2 > TNFR1) and show that TNFalpha significantly augments IFNgamma production from IL-2-/IL-12-treated NK cells in vitro, an effect mimicked by a TNFR2 agonistic antibody. TNFalpha also enhanced murine NK cell IFNgamma production via TNFR2 in vitro. In a mouse model characterized by the hepatic recruitment and activation of NK cells, TNFR2 also regulated NK cell IFNgamma production in vivo. Specifically, in this model, after activation of an innate immune response, hepatic numbers of TNFR2-expressing and IFNgamma producing NK cells were both significantly increased; however, the frequency of IFNgamma-producing hepatic NK cells was significantly reduced in TNFR2-deficient mice. We delineate an important role for TNFalpha, acting through TNFR2, in augmenting cytokine-induced NK cell IFNgamma production in vivo and in vitro, an effect with significant potential implications for the regulation of innate and adaptive immune responses. PMID- 27560482 TI - Efficacy of Resveratrol Supplementation against Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Placebo-Controlled Clinical Trials. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with rising prevalence. Increasing evidence has demonstrated that resveratrol, a dietary phytochemical, is capable of attenuating NAFLD development and progression; however, results from clinical studies are inconsistent and inconclusive. Here, we conducted a meta-analysis to evaluate the efficacy of resveratrol on NAFLD, using several parameters to provide new insights for clinical application. We systematically searched EMBASE, PubMed, Science Citation Index, Elsevier, and Cochrane Library databases for studies published up to date (July 2016), in English, to identify and screen eligible, relevant studies. Either a fixed-effect model or random model was used to estimate mean difference (MD) and 95% confidence intervals (CIs) for the effect of resveratrol on NAFLD. Four randomized, double-blinded, placebo-controlled trials involving 156 patients were included in the meta-analysis. Levels of low-density lipoprotein (MD = 0.47, 95% CI: 0.21, 0.74, P < 0.05) and total cholesterol (MD = 0.49, 95% CI: 0.18, 0.80, P < 0.05) were higher in the resveratrol treatment groups than in placebo control groups, whereas other parameters were not altered. Overall, this study indicates that resveratrol treatment has negligible effects on attenuating NAFLD, given the small improvement in NAFLD features. More high-quality clinical trials of resveratrol for NAFLD are required to confirm these results. PMID- 27560484 TI - Enhanced adhesion and field emission of CuO nanowires synthesized by simply modified thermal oxidation technique. AB - Metal oxide nanowires (NWs) can be easily grown by the thermal oxidation method, but the low adhesion between the NWs and the substrate restricts their practical applications in functional devices. In this work, the conventional hotplate technique is simply modified by introducing one or two stainless steel plates to supply a more stable oxidation environment, which is found to be beneficial to the growth and adhesion of CuO NWs on the Cu substrate. In detail, the Cu foils were heated on the hotplate directly, on one plate over the hotplate, and between two plates over the hotplate at 400 degrees C in ambient condition. It is found that the NWs obtained between two plates exhibit large length and diameter with moderate density. The sufficient activated oxygen, stable temperature, and proper temperature gradient configuration caused by the two plates accelerate the formation of CuO NWs, and result in the longest NWs with enhanced adhesion. The grain-boundary diffusion and Kirkendall effect are proposed to explain the mechanism of NWs growth and the formation of cracks. The NWs obtained between two plates also showed the best field emission properties, with lowest turn-on field (5.31 V MUm(-1)) and threshold field (9.8 V MUm(-1)). Excellent field emission properties and enhanced NW-substrate adhesion indicate that these NW arrays could be potentially used as the cathode of field emission displays. PMID- 27560485 TI - Factors That Modulate Neurogenesis: A Top-Down Approach. AB - Although hippocampal neurogenesis in the adult brain has been conserved across the vertebrate lineage, laboratory studies have primarily examined this phenomenon in rodent models. This approach has been successful in elucidating important factors and mechanisms that can modulate rates of hippocampal neurogenesis, including hormones, environmental complexity, learning and memory, motor stimulation, and stress. However, recent studies have found that neurobiological research on neurogenesis in rodents may not easily translate to, or explain, neurogenesis patterns in nonrodent systems, particularly in species examined in the field. This review examines some of the evolutionary and ecological variables that may also modulate neurogenesis patterns. This 'top down' and more naturalistic approach, which incorporates ecology and natural history, particularly of nonmodel species, may allow for a more comprehensive understanding of the functional significance of neurogenesis. PMID- 27560486 TI - Haemosporidian Prevalence and Parasitemia In the Tufted Titmouse (Baeolophus bicolor). AB - Hemosporidians are a diverse group of blood parasites that infect terrestrial vertebrates worldwide, but there is variability in parasite prevalence and parasitemia with infections ranging from virtually inconsequential to lethal. In this study, we determined prevalence and parasitemia of avian hemosporidians in the Tufted Titmouse ( Baeolophus bicolor ; n = 81). Plasmodium and Parahaemoproteus were detected and quantified from blood samples using microscopy, polymerase chain reaction (PCR), and quantitative PCR. Thirteen mitochondrial cytochrome b lineages of hemosporidian parasites were found, including generalist and specialist lineages, and the data indicate that prevalence is 69.1% (Plasmodium 89.3%; Parahaemoproteus 7.1%; double infection 3.6%). However, parasitemia was low in all infected birds. Seasonally, parasite prevalence varied significantly, although prevalence and parasitemia were not associated with host sex, age, or health. Observations of infection in this naturally infected bird provide details on host susceptibility that are applicable to the understanding of hemosporidian parasites in other avian hosts. PMID- 27560487 TI - Erratum: Determining Chemically and Spatially Resolved Atomic Profile of Low Contrast Interface Structure with High Resolution. PMID- 27560488 TI - Methylation of the Sox9 and Oct4 promoters and its correlation with gene expression during testicular development in the laboratory mouse. AB - Sox9 and Oct4 are two important regulatory factors involved in mammalian development. Sox9, a member of the group E Sox transcription factor family, has a crucial role in the development of the genitourinary system, while Oct4, commonly known as octamer binding transcription factor 4, belongs to class V of the transcription family. The expression of these two proteins exhibits a dynamic pattern with regard to their expression sites and levels. The aim of this study was to investigate the role of de novo methylation in the regulation of the tissue- and site-specific expression of these proteins. The dynamics of the de novo methylation of 15 CpGs and six CpGs in Sox9 and Oct4 respectively, was studied with sodium bisulfite genomic DNA sequencing in mouse testis at different developmental stages. Consistent methylation of three CpGs was observed in adult ovary in which the expression of Sox9 was feeble, while the level of methylation in somatic tissue was greater in Oct4 compared to germinal tissue. The promoter chromatin status of Sox9 was also studied with a chromatin immune-precipitation assay. PMID- 27560489 TI - Downstream extraction process development for recovery of organic acids from a fermentation broth. AB - The present study focused on organic acids (OAs) recovery from an acidogenic fermentation broth, which is the main problem regarding the use of OAs for production of ester-based new generation biofuels or other applications. Specifically, 10 solvents were evaluated for OAs recovery from aqueous media and fermentation broths. The effects of pH, solvent/OAs solution ratios and application of successive extractions were studied. The 1:1 solvent/OAs ratio showed the best recovery rates in most cases. Butyric and isobutyric acids showed the highest recovery rates (80-90%), while lactic, succinic, and acetic acids were poorly recovered (up to 45%). The OAs recovery was significantly improved by successive 10-min extractions. Alcohols presented the best extraction performance. The process using repeated extractions with 3-methyl-1-butanol led to the highest OAs recovery. However, 1-butanol can be considered as the most cost-effective option taking into account its price and availability. PMID- 27560490 TI - Chitosan and gelatin based biodegradable packaging films with UV-light protection. AB - Biopolymers are polymers obtained from biological origins and used for various biological and industrial applications. A biopolymer should be non-toxic, non antigenic, non-irritant, non-carcinogenic, sterilisable and adequately available for their widespread applications. In this study, chitosan (CS) and gelatin (GL) based films were prepared to be used as biodegradable packaging films. CS was blended with GL to improve various physicochemical properties. The blended CSGL films were crosslinked with boric acid (BA) to improve various properties viz. light barrier properties, Water Vapour Permeability (WVP), moisture content (%), Total Solubility Matter (TSM), most important to improve the strength. The studies of transparency, X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and optical microscopy confirms that the synthesized films were found to be transparent and homogenous indicating good compatibility among different components. The synthesized CS and GL based films showed UV-light barrier properties as supported by data. The tensile strength of films increases, decreases water solubility, moisture content (%) and WVP on crosslinking. In order to make the crosslinked films more flexible, Polyethylene glycol was used as plasticizer, making the films more flexible and transparent. This study indicates that these biodegradable CS and GL based films are potent to be used as packing films. PMID- 27560491 TI - Positive and Negative Thinking in Tinnitus: Factor Structure of the Tinnitus Cognitions Questionnaire. AB - OBJECTIVES: Researchers and clinicians consider thinking to be important in the development and maintenance of tinnitus distress, and altering thoughts or thinking style is an object of many forms of psychological therapy for tinnitus. Those working with people with tinnitus require a reliable, psychometrically robust means of measuring both positive and negative thinking related to it. The Tinnitus Cognitions Questionnaire (TCQ) was designed as such a measure and its authors showed it to be reliable, with good psychometric properties. However, no research teams have yet carried out independent validation. This study aimed to use the TCQ to investigate thinking amongst members of the general population with both bothersome and nonbothersome tinnitus and also to verify its factor structure. DESIGN: Three hundred forty-two members of the public with tinnitus completed the TCQ online or on paper. They also rated their tinnitus on a scale as "not a problem," "a small problem," "a moderate problem," "a big problem," or a "very big problem." The authors tested the original factor structure of the TCQ using confirmatory factor analysis and then calculated the mean scores for each item, comparing mean total scores across "problem categories" for the full questionnaire and for the positive and negative subscales. RESULTS: The original two-factor structure of the TCQ was a good fit to the data when the correlation between positive and negative factors was fixed at zero (root mean square error of approximation = 0.064, 90% confidence interval = 0.058 to 0.070). Items pertaining to wishing the tinnitus would go away and despairing that it would ever get better had the highest mean scores. The mean total score for the "no problem" group (M = 31.17, SD = 16.03) was not significantly different from the mean total score for the "small problem" group (M = 34.00, SD = 12.44, p = 0.99). Differences between mean scores for all other groups were statistically significant. For the negative subscale, differences were statistically significant between all problem categories. For the positive subscale, the differences between mean scores were only statistically significant for the "no problem" group (M = 28.40, SD = 17.11) compared with the "moderate problem" group (M = 18.55, SD = 8.64, p = 0.02) and for the "moderate problem" group compared with the "very big problem" group (M = 26.79, SD = 11.66, p = 0.002). Positive and negative factors were uncorrelated (rho = -0.03.) CONCLUSIONS:: The TCQ is a valid measure of positive and negative thinking in tinnitus, and the authors recommend its use in research and therapeutic settings. Negative thinking appears to be associated with more problematic tinnitus, but positive thinking is not associated with unproblematic tinnitus, suggesting that reducing negative thinking may be more important than teaching positive thinking in therapy. PMID- 27560492 TI - Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids. AB - OBJECTIVES: The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones. DESIGN: Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus. RESULTS: In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation. CONCLUSIONS: The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs. PMID- 27560493 TI - Conformationally Distorted pi-Conjugation for Reaction-Based Detection of Nickel: Fluorescence Turn-on by Twist-and-Fragment. AB - A conformationally twisted N-arylbenzotriazole was designed as a fluorescence turn-on molecular probe. Under ambient conditions, metal-catalyzed deallylation reactions restore an intense blue emission. This reaction scheme is applicable exclusively to Group 10 transition metal ions and optimized, in particular, for nickel to allow sub-micromolar detection with no competition from other first-row transition-metal ions. PMID- 27560496 TI - High internal phase emulsion with double emulsion morphology and their templated porous polymer systems. AB - This paper reports synthesis of the first high internal phase emulsion (HIPE) system with double emulsion (DE) morphology (HIPE-DE). HIPE is a highly concentrated but highly stable emulsion system, which has a dispersed/internal phase fraction over 74vol%. DE represents an emulsion system that hierarchically encapsulates two immiscible phases. The combination of HIPE and DE provides an efficient method for fabrication of complex structures. In this work, HIPE-DE having a water-in-oil-in-water (W/O/W) morphology has been prepared for the first time via a simple one-step emulsification method with poly(2-(diethylamino)ethyl methacrylate) (PDEA) microgel particles as Pickering stabilizer. An oil phase fraction up to 90vol% was achieved by optimizing the microgel concentration in aqueous phase. The mechanism of the DE formation has been elucidated. It was found that while PDEA microgels stabilized the oil droplets in water, small amount protonated DEA monomers acted as surfactant and formed water-containing micelles inside the oil droplets. It was demonstrated that the W/O/W HIPE-DE could be precisely converted into porous polymer structures. With styrene as the oil phase in W/O/W HIPE-DE, porous polystyrene particles were obtained upon polymerization. With dissolved acrylamide as the aqueous phase and toluene as the continuous phase, porous polyacrylamide matrixes were prepared. Elevating temperature required for polymerization did not change the W/O/W HIPE-DE morphologies. This simple approach provides a versatile platform for synthesis of a variety of porous polymer systems. PMID- 27560494 TI - SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury. AB - Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role. PMID- 27560495 TI - Maternal Blood Lipid Profile during Pregnancy and Associations with Child Adiposity: Findings from the ROLO Study. AB - BACKGROUND: The in-utero environment affects fetal development; it is vital to understand how maternal diet during pregnancy influences childhood body composition. While research indicates that triglycerides in hyperglycaemic women may increase birth weight, little is known about this relationship in euglycemic women. This study examines the relationship between maternal blood lipid status and infant adiposity up to 2 years of age. METHODS: Data from 331 mother-child pairs from the ROLO longitudinal birth cohort study was analysed. Maternal dietary intakes were recorded and fasting blood lipids, leptin and HOMA were measured in early and late pregnancy and cord blood. Infant anthropometric measurements and skin-fold thicknesses were recorded at birth, 6 months and 2 years. Correlation and regression analyses were used to explore associations between maternal blood lipid status and infant adiposity. RESULTS: All maternal blood lipids increased significantly during pregnancy. Maternal dietary fat intake was positively associated with total cholesterol levels in early pregnancy. Late pregnancy triglycerides were positively associated with birth weight (P = 0.03) while cord blood triglycerides were negatively associated with birth weight (P = 0.01). Cord HDL-C was negatively associated with infant weight at 6 months (P = 0.005). No other maternal blood lipids were associated with infant weight or adiposity up to 2 years of age. CONCLUSION: Maternal and fetal triglycerides were associated with birth weight and cord HDL-C with weight at 6 months. Thus, maternal lipid concentrations may exert in-utero influences on infant body composition. There may be potential to modulate infant body composition through alteration of maternal diet during pregnancy. PMID- 27560497 TI - Zinc-oxide-silica-silver nanocomposite: Unique one-pot synthesis and enhanced catalytic and anti-bacterial performance. AB - We describe herein a unique approach to synthesize zinc oxide-silica-silver (ZnO SiO2-Ag) nanocomposite, in a simple, one-pot process. The typical process for ZnO synthesis by alkaline precipitation of zinc salts has been tweaked to replace alkali by alkaline sodium silicate. The free acid from zinc salts helps in the synthesis of silica nanoparticles, whereas the alkalinity of sodium silicate precipitates the zinc salts. Addition of silver ions into the reaction pot prior to addition of sodium silicate, and subsequent reduction by borohydride, gives additional functionality of metallic centres for catalytic applications. The synthesis strategy is based on our recent work typically involving acid-base type of cross-reactions and demonstrates a novel strategy to synthesize nanocomposites in a one-pot approach. Each component in the composite offers a unique feature. ZnO besides displaying mild catalytic and anti-bacterial behaviour is an excellent and a cheap 3-D support for heterogeneous catalysis. Silver nanoparticles enhance the catalytic & anti-bacterial properties of ZnO. Silica is an important part of the composite; which not only "glues" the two nanoparticles thereby stabilizing the nanocomposite, but also significantly enhances the surface area of the composite; which is an attractive feature of any catalyst composite. The nanocomposite is found to show excellent catalytic performance with very high turnover frequencies (TOFs) when studied for catalytic reduction of Rhodamine B (RhB) and 4-Nitrophenol (4-NP). Additionally, the composite has been tested for its anti-bacterial properties on three different bacterial strains i.e. E. coli, B. Cereus and Bacillus firmus. The mechanism for enhancement of catalytic performance has been probed by understanding the role of silica in offering accessibility to the catalyst via its porous high surface area network. The nanocomposite has been characterized by a host of different analytical techniques. The uniqueness of our product and process stems from the novel synthesis strategy, the choice and combination of the three moieties, increased surface area offered by silica, and cost effectiveness, thereby making our product and process commercially viable and sustainable for industrial applications. PMID- 27560498 TI - Collecting Kinematic Data on a Ski Track with Optoelectronic Stereophotogrammetry: A Methodological Study Assessing the Feasibility of Bringing the Biomechanics Lab to the Field. AB - In the laboratory, optoelectronic stereophotogrammetry is one of the most commonly used motion capture systems; particularly, when position- or orientation related analyses of human movements are intended. However, for many applied research questions, field experiments are indispensable, and it is not a priori clear whether optoelectronic stereophotogrammetric systems can be expected to perform similarly to in-lab experiments. This study aimed to assess the instrumental errors of kinematic data collected on a ski track using optoelectronic stereophotogrammetry, and to investigate the magnitudes of additional skiing-specific errors and soft tissue/suit artifacts. During a field experiment, the kinematic data of different static and dynamic tasks were captured by the use of 24 infrared-cameras. The distances between three passive markers attached to a rigid bar were stereophotogrammetrically reconstructed and, subsequently, were compared to the manufacturer-specified exact values. While at rest or skiing at low speed, the optoelectronic stereophotogrammetric system's accuracy and precision for determining inter-marker distances were found to be comparable to those known for in-lab experiments (< 1 mm). However, when measuring a skier's kinematics under "typical" skiing conditions (i.e., high speeds, inclined/angulated postures and moderate snow spraying), additional errors were found to occur for distances between equipment-fixed markers (total measurement errors: 2.3 +/- 2.2 mm). Moreover, for distances between skin-fixed markers, such as the anterior hip markers, additional artifacts were observed (total measurement errors: 8.3 +/- 7.1 mm). In summary, these values can be considered sufficient for the detection of meaningful position- or orientation related differences in alpine skiing. However, it must be emphasized that the use of optoelectronic stereophotogrammetry on a ski track is seriously constrained by limited practical usability, small-sized capture volumes and the occurrence of extensive snow spraying (which results in marker obscuration). The latter limitation possibly might be overcome by the use of more sophisticated cluster based marker sets. PMID- 27560499 TI - Coupled Socio-Environmental Changes Triggered Indigenous Aymara Depopulation of the Semiarid Andes of Tarapaca-Chile during the Late 19th-20th Centuries. AB - Socio-economic and environmental changes are well known causes of demographic collapse of agrarian cultures. The collapse of human societies is a complex phenomenon where historical and cultural dimensions play a key role, and they may interact with the environmental context. However, the importance of the interaction between socio-economic and climatic factors in explaining possible breakdowns in Native American societies has been poorly explored. The aim of this study is to test the role of socio-economic causes and rainfall variability in the collapse suffered by the Aymara people of the semiarid Andean region of Tarapaca during the period 1820-1970. Our motivation is to demonstrate that simple population dynamic models can be helpful in understanding the causes and relative importance of population changes in Andean agro-pastoral societies in responses to socio-environmental variability. Simple logistic models that combine the effects of external socio-economic causes and past rainfall variability (inferred from Gross Domestic Product [GDP] and tree-rings, respectively) were quite accurate in predicting the sustained population decline of the Aymara people. Our results suggest that the depopulation in the semiarid Tarapaca province was caused by the interaction among external socio-economic pressures given by the economic growth of the lowlands and demands for labor coupled with a persistent decline in rainfall. This study constitutes an example of how applied ecological knowledge, in particular the application of the logistic equation and theories pertaining to nonlinear population dynamics and exogenous perturbations, can be used to better understand major demographic changes in human societies. PMID- 27560500 TI - Laparoscopic Management of Dialysate Leakage Secondary to Necrotic Peritoneum. AB - Peritoneal dialysate leakage is a well-known complication of continuous ambulatory peritoneal dialysis (CAPD). In late leakage, it is usually managed conservatively and subsequently converted to hemodialysis. We hereby report a case of peritoneal dialysate leakage secondary to necrotic peritoneum, which was managed by laparoscopic excision of the affected peritoneum. Regeneration of new peritoneum was documented and the patient could resume CAPD successfully. PMID- 27560501 TI - Relationship of Predicted Risk of Developing Invasive Breast Cancer, as Assessed with Three Models, and Breast Cancer Mortality among Breast Cancer Patients. AB - PURPOSE: Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown. METHODS: Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC) for 37,939 invasive breast cancers (1996-2007), we estimated 5-year breast cancer risk (<1%; 1-1.66%; >=1.67%) with three models: BCSC 1-year risk model (BCSC-1; adapted to 5-year predictions); Breast Cancer Risk Assessment Tool (BCRAT); and BCSC 5-year risk model (BCSC-5). Breast cancer-specific mortality post-diagnosis (range: 1-13 years; median: 5.4-5.6 years) was related to predicted risk of developing breast cancer using unadjusted Cox proportional hazards models, and in age-stratified (35-44; 45-54; 55-69; 70-89 years) models adjusted for continuous age, BCSC registry, calendar period, income, mode of presentation, stage and treatment. Mean age at diagnosis was 60 years. RESULTS: Of 6,021 deaths, 2,993 (49.7%) were ascribed to breast cancer. In unadjusted case only analyses, predicted breast cancer risk >=1.67% versus <1.0% was associated with lower risk of breast cancer death; BCSC-1: hazard ratio (HR) = 0.82 (95% CI = 0.75-0.90); BCRAT: HR = 0.72 (95% CI = 0.65-0.81) and BCSC-5: HR = 0.84 (95% CI = 0.75-0.94). Age-stratified, adjusted models showed similar, although mostly non significant HRs. Among women ages 55-69 years, HRs approximated 1.0. Generally, higher predicted risk was inversely related to percentages of cancers with unfavorable prognostic characteristics, especially among women 35-44 years. CONCLUSIONS: Among cases assessed with three models, higher predicted risk of developing breast cancer was not associated with greater risk of breast cancer death; thus, these models would have limited utility in planning studies to evaluate breast cancer mortality reduction strategies. Further, when offering women counseling, it may be useful to note that high predicted risk of developing breast cancer does not imply that if cancer develops it will behave aggressively. PMID- 27560502 TI - The Effect of Vector Silencing during Picornavirus Vaccination against Experimental Melanoma and Glioma. AB - Virus vector-based vaccination against tumor-specific antigens remains a promising therapeutic approach to overcome the immune suppressive tumor microenvironment. However, the extent that the desired CD8 T cell response against the targeted tumor antigen is impacted by the CD8 T cell response against the virus vector is unclear. To address this question, we used picornavirus vaccination with Theiler's murine encephalomyelitis virus (TMEV) as our vector against tumor-expressed ovalbumin (OVA257-264) antigen in both the B16-OVA murine melanoma and GL261-quad cassette murine glioma models. Prior to vaccination, we employed vector silencing to inhibit the CD8 T cell response against the immunodominant TMEV antigen, VP2121-130. We then monitored the resulting effect on the CD8 T cell response against the targeted tumor-specific antigen, ovalbumin. We demonstrate that employing vector silencing in the context of B16 OVA melanoma does not reduce tumor burden or improve survival, while TMEV-OVA vaccination without vector silencing controls tumor burden. Meanwhile, employing vector silencing during picornavirus vaccination against the GL261-quad cassette glioma resulted in a lower frequency of tumor antigen-specific CD8 T cells. The results of this study are relevant to antigen-specific immunotherapy, in that the virus vector-specific CD8 T cell response is not competing with tumor antigen specific CD8 T cells. Furthermore, vector silencing may have the adverse consequence of reducing the tumor antigen-specific CD8 T cell response, as demonstrated by our findings in the GL261-quad cassette model. PMID- 27560503 TI - Utilization Patterns of Topical Intranasal Steroid Therapy for Chronic Rhinosinusitis: A Canadian Population-Based Analysis. AB - Importance: Practice guidelines have provided a strong recommendation for the daily use of topical intranasal steroid therapy for patients with chronic rhinosinusitis (CRS). Deficiencies in utilization of intranasal steroid therapy may represent a gap in quality of care. Objective: To evaluate the utilization patterns of topical intranasal steroid therapy for CRS in the Canadian population. Design, Setting, and Participants: Retrospective review of a Canadian population-based health care administrative database. A validated case definition for CRS was applied, and the utilization of topical intranasal steroid therapy within this cohort was quantified during the 2014-2015 fiscal year. Interventions: Intranasal steroid spray for CRS. Main Outcomes and Measures: Primary outcome was the rate (per 100 patients) and quantity (per patient) of intranasal steroid spray utilization in patients with CRS. Secondary outcome was the geographic variation in the rate and quantity of intranasal steroid spray utilization for CRS. Results: A total of 19 057 adult patients with CRS were evaluated. The overall rate of intranasal steroid spray utilization was 20.1 per 100 patients with CRS (3821 of 19 057). In the 3821 patients with CRS who used an intranasal steroid spray during 2014 to 2015, the mean quantity of utilization was 2.4 U (1 U = 1 bottle per month) per patient (9314 U divided by 3821 patients with CRS). There was large geographic variation in both the rate and quantity of intranasal steroid spray utilization (P < .001 for both comparisons). Conclusions and Relevance: Topical intranasal steroid therapy continues to be underutilized for patients with CRS. Given the negative impact of low-quality medical care, outcomes from this study indicate a need to further evaluate factors leading to the underutilization of a recommended treatment in patients with CRS to improve overall health system performance. PMID- 27560504 TI - Effect of Lining Materials on Shear Bond Strength for Composite Restorations In Vitro. AB - This study evaluated the influence of liner agents placed under resin composite restorations on shear bond strength (SBS) to dentin. A total of 40 extracted bovine incisors were used. Enamel surfaces were ground to expose a flat dentin area of 7 mm in diameter. Teeth were divided into four groups according to tested liners: Group 1 (control) used no liner; Group 2 used a resin-modified glass ionomer cement liner (Vitrebond Plus, 3M ESPE); Group 3 used a light-activated calcium hydroxide resin liner (Ultra-Blend Plus, Ultradent); and Group 4 used a polyacrylic acid surface treatment + conventional glass-ionomer cement liner (Vidrion F, SSWhite). All groups were subjected to bonding procedures with Single Bond (3M ESPE) and 4-mm-thick buildups of resin composite were fabricated. Artificial aging was performed, and the specimens were submitted to mechanical shear testing. One-way analysis of variance (ANOVA) revealed significant differences among liners (P = .00). Group 4 showed the highest SBS. Group 1 showed significantly higher mean SBS compared with Group 3. Results showed that SBS is improved when using polyacrylic acid surface treatment + conventional glass-ionomer cement and decreased when using light-activated calcium hydroxide when compared with no liner. Polyacrylic acid surface treatment + conventional glass-ionomer cement as a liner placed under adhesion surface can improve the shear bond strength between dentin and resin, while light-activated calcium hydroxide resin should be used restrictedly in very deep cavities, because they may reduce the bond strength of the restoration submitted to masticatory forces and temperature changes in the oral environment. PMID- 27560505 TI - Xenogeneic Collagen Matrix Versus Connective Tissue Graft: Case Series of Various Gingival Recession Treatments. AB - A xenogeneic collagen matrix recently has been suggested as an alternative to connective tissue graft for the treatment of gingival recession. The matrix avoids the second surgical site, and as a consequence could decrease surgical morbidity. This new matrix was used in various clinical situations and compared to connective tissue graft (CTG) in a split-mouth design case series. A total of 17 recessions were treated with a coronally advanced flap, 9 with CTG, and 8 with the matrix. Mean recession reduction was 2.00 mm with the CTG and 2.00 mm with the matrix. No significant statistical differences between the techniques were observed in this case report. PMID- 27560506 TI - Histologic and Clinical Study of Gingival Recession Treated with Subepithelial Connective Tissue Graft (SCTG): A Case Report. AB - Subepithelial connective tissue graft (SCTG) is considered the gold standard for treatment of gingival recessions. For ethical reasons, most studies report only clinical and not histologic results. A 20-year-old woman presenting with a localized gingival recession of 5 mm in the mandibular left central incisor was treated with SCTG. According to the initial treatment plan, the tooth was extracted 11 months later and a histologic study was performed, revealing new attachment of connective tissue with collagen fibers that were directly inserted in a perpendicular way into dentin areas and new cement areas (1.37 mm). PMID- 27560507 TI - Response of Dental Pulp Stem Cells to Synthetic, Allograft, and Xenograft Bone Scaffolds. AB - Different degrees of clinical success have been reported for synthetic, allograft, and xenograft bone substitutes in human trials. Although these substitutes have been clinically investigated, their in vitro effects on cell differentiation remain unclear. Proliferation, differentiation, and attachment of dental pulp stem cells (DPSCs) to beta-tricalcium phosphate (beta-TCP), freeze dried bone allograft (FDBA), and deproteinized bovine bone mineral (DBBM) were compared in this study. MTT assay, measurement of total DNA, and reverse transcriptase polymerase chain reaction were performed. beta-TCP had the highest potential for DPSC attachment and proliferation, while FDBA induced osteoblastic differentiation of DPSCs. Further in vivo investigations are necessary to select a clinically appropriate scaffold. PMID- 27560509 TI - Microsurgical Instruments in Laterally Moved, Coronally Advanced Flap for Miller Class III Isolated Recession Defects: A Randomized Controlled Clinical Trial. AB - The aim of this study was to evaluate the laterally moved coronally advanced flap (LMCAF) technique in which magnified vision was used in conjunction with microsurgical instruments (LMCAF-M), and to compare the results with conventional LMCAF technique (LMCAF-C) in Miller Class III isolated recession-type defects. A total of 50 patients with recessions located at incisors and canines were treated with LMCAF-M or LMCAF-C. Outcome parameters (complete root coverage [CRC] and mean root coverage [MRC]) were assessed 6 months postoperatively. Of the 25 defects in each group, 13 in the LMCAF-M (92.0%) and 17 in the LMCAF-C group (68.0%) exhibited CRC (P < .007). MRC scores were 90.48% for the LMCAF-C group and 97.64% for the LMCAF-M group (P < .04). Patient satisfaction with esthetics and postoperative morbidity were better in the LMCAF-M group (P < .032). This study indicates that performing LMCAF with microsurgical instruments offers definite advantages in terms of CRC and MRC, decreased postoperative morbidity, and increased acceptance by patients. PMID- 27560510 TI - Highly fluorescent 1,2-dihydropyrimido[1,6-alpha]indole: an efficient metal free synthesis and photophysical study. AB - A metal free route to highly fluorescent 1,2-dihydropyrimido[1,6-alpha]indole derivatives has been developed via base catalyzed aldol followed by the Mannich reaction of indole-2-carboxaldehyde with ethyl N-arylideneglycinate at room temperature. This transformation consists of the sequential formation of two new bonds to afford highly functionalized pyrimidoindole derivatives under mild reaction conditions. Photophysical properties of the products have also been reported. PMID- 27560511 TI - Rapid Sediment Accumulation Results in High Methane Effluxes from Coastal Sediments. AB - Globally, the methane (CH4) efflux from the ocean to the atmosphere is small, despite high rates of CH4 production in continental shelf and slope environments. This low efflux results from the biological removal of CH4 through anaerobic oxidation with sulfate in marine sediments. In some settings, however, pore water CH4 is found throughout the sulfate-bearing zone, indicating an apparently inefficient oxidation barrier for CH4. Here we demonstrate that rapid sediment accumulation can explain this limited capacity for CH4 removal in coastal sediments. In a saline coastal reservoir (Lake Grevelingen, The Netherlands), we observed high diffusive CH4 effluxes from the sediment into the overlying water column (0.2-0.8 mol m-2 yr-1) during multiple years. Linear pore water CH4 profiles and the absence of an isotopic enrichment commonly associated with CH4 oxidation in a zone with high rates of sulfate reduction (50-170 nmol cm-3 d-1) both suggest that CH4 is bypassing the zone of sulfate reduction. We propose that the rapid sediment accumulation at this site (~ 13 cm yr-1) reduces the residence time of the CH4 oxidizing microorganisms in the sulfate/methane transition zone (< 5 years), thus making it difficult for these slow growing methanotrophic communities to build-up sufficient biomass to efficiently remove pore water CH4. In addition, our results indicate that the high input of organic matter (~ 91 mol C m-2 yr-1) allows for the co-occurrence of different dissimilatory respiration processes, such as (acetotrophic) methanogenesis and sulfate reduction in the surface sediments by providing abundant substrate. We conclude that anthropogenic eutrophication and rapid sediment accumulation likely increase the release of CH4 from coastal sediments. PMID- 27560512 TI - Motor Skills and Exercise Capacity Are Associated with Objective Measures of Cognitive Functions and Academic Performance in Preadolescent Children. AB - OBJECTIVE: To investigate associations between motor skills, exercise capacity and cognitive functions, and evaluate how they correlate to academic performance in mathematics and reading comprehension using standardised, objective tests. METHODS: This cross-sectional study included 423 Danish children (age: 9.29+/ 0.35 years, 209 girls). Fine and gross motor skills were evaluated in a visuomotor accuracy-tracking task, and a whole-body coordination task, respectively. Exercise capacity was estimated from the Yo-Yo intermittent recovery level 1 children's test (YYIR1C). Selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess different domains of cognitive functions, including sustained attention, spatial working memory, episodic and semantic memory, and processing speed. Linear mixed-effects models were used to investigate associations between these measures and the relationship with standard tests of academic performance in mathematics and reading comprehension. RESULTS: Both fine and gross motor skills were associated with better performance in all five tested cognitive domains (all P<0.001), whereas exercise capacity was only associated with better sustained attention (P<0.046) and spatial working memory (P<0.038). Fine and gross motor skills (all P<0.001), exercise capacity and cognitive functions such as working memory, episodic memory, sustained attention and processing speed were all associated with better performance in mathematics and reading comprehension. CONCLUSIONS: The data demonstrate that fine and gross motor skills are positively correlated with several aspects of cognitive functions and with academic performance in both mathematics and reading comprehension. Moreover, exercise capacity was associated with academic performance and performance in some cognitive domains. Future interventions should investigate associations between changes in motor skills, exercise capacity, cognitive functions, and academic performance to elucidate the causality of these associations. PMID- 27560513 TI - Entangling Credit and Funding Shocks in Interbank Markets. AB - Credit and liquidity shocks represent main channels of financial contagion for interbank lending markets. On one hand, banks face potential losses whenever their counterparties are under distress and thus unable to fulfill their obligations. On the other hand, solvency constraints may force banks to recover lost fundings by selling their illiquid assets, resulting in effective losses in the presence of fire sales-that is, when funding shortcomings are widespread over the market. Because of the complex structure of the network of interbank exposures, these losses reverberate among banks and eventually get amplified, with potentially catastrophic consequences for the whole financial system. Inspired by the recently proposed Debt Rank, in this work we define a systemic risk metric that estimates the potential amplification of losses in interbank markets accounting for both credit and liquidity contagion channels: the Debt Solvency Rank. We implement this framework on a dataset of 183 European banks that were publicly traded between 2004 and 2013, showing indeed that liquidity spillovers substantially increase systemic risk, and thus cannot be neglected in stress-test scenarios. We also provide additional evidence that the interbank market was extremely fragile up to the global financial crisis, becoming slightly more robust only afterwards. PMID- 27560514 TI - Correction: Robust Bayesian Fluorescence Lifetime Estimation, Decay Model Selection and Instrument Response Determination for Low-Intensity FLIM Imaging. AB - [This corrects the article DOI: 10.1371/journal.pone.0158404.]. PMID- 27560515 TI - T2-Imaging to Assess Cerebral Oxygen Extraction Fraction in Carotid Occlusive Disease: Influence of Cerebral Autoregulation and Cerebral Blood Volume. AB - PURPOSE: Quantitative T2'-mapping detects regional changes of the relation of oxygenated and deoxygenated hemoglobin (Hb) by using their different magnetic properties in gradient echo imaging and might therefore be a surrogate marker of increased oxygen extraction fraction (OEF) in cerebral hypoperfusion. Since elevations of cerebral blood volume (CBV) with consecutive accumulation of Hb might also increase the fraction of deoxygenated Hb and, through this, decrease the T2'-values in these patients we evaluated the relationship between T2'-values and CBV in patients with unilateral high-grade large-artery stenosis. MATERIALS AND METHODS: Data from 16 patients (13 male, 3 female; mean age 53 years) with unilateral symptomatic or asymptomatic high-grade internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis/occlusion were analyzed. MRI included perfusion-weighted imaging and high-resolution T2'-mapping. Representative relative (r)CBV-values were analyzed in areas of decreased T2' with different degrees of perfusion delay and compared to corresponding contralateral areas. RESULTS: No significant elevations in cerebral rCBV were detected within areas with significantly decreased T2'-values. In contrast, rCBV was significantly decreased (p<0.05) in regions with severe perfusion delay and decreased T2'. Furthermore, no significant correlation between T2'- and rCBV-values was found. CONCLUSIONS: rCBV is not significantly increased in areas of decreased T2' and in areas of restricted perfusion in patients with unilateral high-grade stenosis. Therefore, T2' should only be influenced by changes of oxygen metabolism, regarding our patient collective especially by an increase of the OEF. T2' mapping is suitable to detect altered oxygen consumption in chronic cerebrovascular disease. PMID- 27560516 TI - Meeting expectations. PMID- 27560517 TI - New Drugs 2016, part 3. PMID- 27560519 TI - DockQ: A Quality Measure for Protein-Protein Docking Models. AB - The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10A) might still qualify as 'acceptable' with a descent Fnat (>0.50) and iRMS (<3.0A). This is also the reason why the so called CAPRI criteria for assessing the quality of docking models is defined by applying various ad-hoc cutoffs on these measures to classify a docking model into the four classes: Incorrect, Acceptable, Medium, or High quality. This classification has been useful in CAPRI, but since models are grouped in only four bins it is also rather limiting, making it difficult to rank models, correlate with scoring functions or use it as target function in machine learning algorithms. Here, we present DockQ, a continuous protein-protein docking model quality measure derived by combining Fnat, LRMS, and iRMS to a single score in the range [0, 1] that can be used to assess the quality of protein docking models. By using DockQ on CAPRI models it is possible to almost completely reproduce the original CAPRI classification into Incorrect, Acceptable, Medium and High quality. An average PPV of 94% at 90% Recall demonstrating that there is no need to apply predefined ad-hoc cutoffs to classify docking models. Since DockQ recapitulates the CAPRI classification almost perfectly, it can be viewed as a higher resolution version of the CAPRI classification, making it possible to estimate model quality in a more quantitative way using Z-scores or sum of top ranked models, which has been so valuable for the CASP community. The possibility to directly correlate a quality measure to a scoring function has been crucial for the development of scoring functions for protein structure prediction, and DockQ should be useful in a similar development in the protein docking field. DockQ is available at http://github.com/bjornwallner/DockQ/. PMID- 27560518 TI - Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3alpha/beta Pathway. AB - Porcine epidemic diarrhea virus (PEDV) has recently caused high mortality in suckling piglets with subsequent large economic losses to the swine industry. Many intracellular signaling pathways, including the phosphatidylinositol 3 kinase (PI3K)/Akt pathway, are activated by viral infection. The PI3K/Akt pathway is an important cellular pathway that has been shown to be required for virus replication. In the present study, we found that the PEDV JS-2013 strain activated Akt in Vero cells at early (5-15 min) and late stages (8-10 h) of infection. Inhibiting PI3K, an upstream activator of Akt, enhanced PEDV replication. Inhibiting GSK-3alpha/beta, one of the downstream effectors of PI3K/Akt pathway and regulated by Akt during PEDV infected Vero cells, also enhanced PEDV replication. Collectively, our data suggest that PI3K/Akt/GSK 3alpha/beta signaling pathway is activated by PEDV and functions in inhibiting PEDV replication. PMID- 27560522 TI - Pulsed Radiofrequency and Coccygodynia. PMID- 27560521 TI - Increased Plasma Matrix Metalloproteinase-9 Levels Contribute to Intracerebral Hemorrhage during Thrombolysis after Concomitant Stroke and Influenza Infection. AB - BACKGROUND: Thrombolysis is the only approved therapy for acute stroke. However, life-threatening complications such as intracerebral hemorrhage (ICH) can develop after intravenous administration of tissue plasminogen activator (tPA). Both infection and thrombolysis during cerebral ischemia disrupt the blood-brain barrier (BBB). tPA can induce matrix metalloproteinase-9 (MMP-9), which is known to be involved in BBB disruption. However, it has still not been investigated whether preexisting influenza virus infection during thrombolysis after acute stroke affects systemic levels of MMP-9 and its inhibitor TIMP-1 and whether increased systemic MMP-9 levels affect ICH. This study aimed to investigate the influence of influenza virus infection on plasma levels of MMP-9 and TIMP-1 after thrombolysis in acute stroke, and to determine whether the infection correlates with intracerebral bleeding. METHODS: C57BL/6 mice were infected by administering 1 * 105 plaque-forming units of human influenza (H1N1) virus intranasally. After 3 days of infection the middle cerebral artery was occluded for 45 min and then reperfused. Intravenous tPA (10 mg/kg) treatment was started 10 min after stroke onset. Twenty-four hours after stroke onset, mice were deeply anesthetized with ketamine, venous blood was drawn from the caval vein and centrifuged at 2,000 rpm, and the supernatant was collected and frozen at -80 degrees C. Plasma levels of MMP-9 and TIMP-1 were quantified by using ELISA. RESULTS: After stroke, plasma MMP-9 was significantly increased in mice with a concomitant influenza infection that were treated with tPA (9.99 +/- 0.62 ng/ml, n = 7) as compared to noninfected control mice that were treated with tPA (4.74 +/- 0.48 ng/ml, n = 8). Moreover, plasma levels of TIMP-1, an inhibitor of MMP-9, were also significantly increased in mice treated with tPA after concomitant infection and stroke (42.17 +/- 7.02 ng/ml, n = 7) as compared to noninfected control mice that were treated with tPA after stroke (20.22 +/- 2.12 ng/ml, n = 8). MMP-9 values significantly correlated with intracerebral hemoglobin levels in animals treated with tPA after stroke (p = 0.028, r = 0.76, n = 8) and after concomitant stroke and infection (p = 0.039, r = 0.78, n = 7). CONCLUSION: Preexisting influenza A virus infection led to increased plasma MMP-9 and TIMP-1 levels in mice undergoing thrombolysis after induced stroke. MMP-9 levels closely correlated with intracerebral bleeding after thrombolysis during concomitant infection and stroke. Thus, our data indicate that thrombolysis may be dangerous during influenza infection. MMP-9 inhibitors might be considered to reduce the side effects of thrombolysis during concomitant infection and stroke. PMID- 27560523 TI - Herpes Zoster Brachial Plexopathy: Direct Steroid Injection. AB - Herpes zoster (shingles) is a viral disease, characterized by painful skin eruptions and neuropathic sensory symptoms. Motor involvement and brachial plexus involvement in herpes zoster are rare conditions. Together with antiviral medication and pain therapy, palliative and supportive modalities take an important role in the treatment of herpes zoster. It is well documented in previous reports that oral or intravenous steroid administrations may be additive in management. In this case report, positive effects of direct steroid injection onto the brachial plexus via ultrasonography guidance in a patient with motor weakness due to herpes zoster involvement of brachial plexus is presented. PMID- 27560520 TI - Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. AB - Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10-8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis. PMID- 27560524 TI - Ancient Olfactory Schwannoma - Case Report and Literature Review. AB - Intracranial schwannomas are benign tumors that arise from Schwann cells. Since it is well known that optic and olfactory nerves do not have a Schwann cell sheath, schwannoma should not develop from these nerves. We report a very unusual case of a 73-year-old female who presented with generalized seizures and had radiological features of an intracranial aneurysm. Additional imaging showed an extracerebral mass 2.5 x 2.0 cm in size, which most likely corresponded to a meningioma. It was resected in total. Subsequent histological analysis revealed that the tumor was in fact ancient schwannoma WHO grade I. Only about 41 case of olfactory schwannoma have been reported in the literature. Olfactory groove schwannomas are extremely rare tumors, occurring less frequently than any other intracranial nerve schwannoma. As in this case, the schwannoma should be included in the differential diagnosis of the anterior cranial fossa tumor. Further research on the pathogenesis and the origin of olfactory groove schwannoma is needed. PMID- 27560525 TI - Local Tissue Electrical Resistances in Transpedicular Screw Application in the Thoracolumbar Region. AB - AIM: To determine local tissue electrical resistance differences generated during a screw pass from the pedicle to another tissue rather than determining all individual electrical tissue resistance values. MATERIAL AND METHODS: We attempted to measure electrical resistance values of regional tissues in addition to fluoroscopic imaging during application of fixation via a transpedicular screw. We also attempted to detect local tissue electrical resistance alterations in case of malposition of the screw inside the pedicle. For this purpose, local tissue electrical resistances of 10 transpedicular tracks opened with standard track openers bilaterally in 5 vertebrae, and of spinal cord accessed by puncturing the medial walls of three vertebrae in a cadaver were measured. These resistance differences were not only measured in human cadaveric tissue but also in 36 pedicles belonging to a total of 18 vertebrae between Th 1-S1 vertebrae of a sheep cadaver. Both medial and lateral walls were drilled to measure local tissue resistance differences in a sheep cadaver. RESULTS: Our results indicated that local tissue electrical resistance changes were statistically significant in both human and sheep cadaver. CONCLUSION: It is possible to prevent screw malposition using a simple and cheap electrical resistance measurement. Local tissue electrical resistance measurement during transpedicular screw insertion is a safe, simple, cheap, and practical method. PMID- 27560526 TI - Actigraphic Analysis of Patients with Cervical Disc Herniation. AB - AIM: To analyze the relationship between the severity of pain and sleep disorder using wrist actigraphy in patients with cervical disc herniation (CDH). MATERIAL AND METHODS: Fifty patients with the diagnosis of CDH underwent subjective tests and actigraphic analysis in preoperative period, and at the end of postoperative first week and postoperative first month. The data of the subjective tests and actigraphic analysis were compared. RESULTS: There was a strong and statistically significant negative correlation between the subjective tests of Visual Analog Scale (VAS) for Pain 0-1-2 and the objective parameters of Sleep Onset Latency (SOL) 0-1-2 (rs= -0.798, p=0.009 - rs= - 0.832, p=0.006 - rs=- 0.710, p=0.004). There was a positive correlation between the subjective tests of VAS for Pain 0-1 2 and the objective parameters of Sleep Efficiency (SEF) 0-1-2 (rs=0.721, p=0.006 - rs= 0.768, p=0.001 - rs= 0.748, p=0.001). CONCLUSION: Actigraphy may be used for the evaluation of cervical disc surgery, as an alternative and objective test for sleep disorders. PMID- 27560527 TI - Dural Tear: A Feared Complication of Lumbar Discectomy. AB - AIM: To show causes of dural tear in isolated lumbar disc surgery, and to investigate the risk factors. MATERIAL AND METHODS: We retrospectively reviewed 1159 cases (532 females and 627 males) involving patients who underwent a surgery for the treatment of lumbar disc herniation between 2006 and 2013. We have analysed the side of the surgery, level of the operation, first or revision surgery, type of anesthesia and type of surgical procedure for the risk of dural tear. To examine differences between disc levels, we used Chi-square testing for categorical variables and the student's t test for continuous variables. To analyze our data, we used STATA version 12. A "p value" less than 0.05 was considered as statistically significant. RESULTS: A total of 1047 (90.3%) cases were treated with microdiscectomy, and 112 (9.7%) required open discectomy. Overall, 820 (70.7%) and 339 (29.3%) surgeries were performed under epidural and general anesthesia, respectively. Dural tear ratio was 1.20%. In dural tear ratio, there was a significant difference in gender (Female: 1.6%, Male: 0.79%) (p < 0.05). Dural tear ratios at primary disc surgery and at recurrent disc surgery were respectively 0.82% and 7.14% (p < 0.05). Most of the tears were on the right side (11/14) (p < 0.05). 13 dural tear cases (1.58%) were noted in patients who operated under epidural anesthesia (820 cases) compared to 1 (0.29%) under general anesthesia (339 cases) (p < 0.05). CONCLUSION: Recurrent disc surgery, female sex, epidural anesthesia, open discectomy, non-dominant hand usage of surgeon, and upper-level affected lumbar discs were risk factors for intraoperative dural tear during lumbar disc surgery. PMID- 27560528 TI - Cultural Adaptation of the Extended Aberdeen Spine Pain Scale: A Turkish Version Study. AB - AIM: To evaluate the validity and reliability of Turkish version of Extended Aberdeen Spine Pain Scale (EASP). MATERIAL AND METHODS: After cultural adaptation, the questionnaire was administered to 120 patients. Test-retest reliability, internal consistency, construct and criterion validity and responsiveness to treatment were measured. All questionnaires were administered at baseline, 1 day later and at the end of treatment. Patients were assessed with Physical and Mental Component scores of SF-36 (SF-36PCS, SF-36MCS), Beck Depression Inventory (BDI) and Visual Analog Scale for pain (VAS). RESULTS: Retest scores were significant (ICC: 0.878). For internal consistency, Cronbach"s alpha was 0.908, which means all parts of the questionnaire are highly homogenous. For construct validity, Spearman"s Correlation Coefficient was 0.907, which means that items of the questionnaire behaved as expected. For criterion validity of EASP, Spearman"s rho correlations with SF- 36PCS (-0.999), SF-36MCS ( 0.367), BDI (0.350), VASactivity (0.429), VASrest (0.399) and VASsleep (0.308) were found significant (p=0.000). According to responsiveness, EASP, SF-36PCS, VASactivity, VASrest, VASsleep showed significant improvement after the treatment (p=0.000). CONCLUSION: The Turkish version of EASP seems reliable, valid, and responsive. Because of its usefulness for evaluating the whole spine as a functional unit, the EASP can be recommended for clinical trials. PMID- 27560529 TI - Endovascular Treatment for Aneurysmal Subarachnoid Hemorrhage with Neurogenic Pulmonary Edema in the Acute Stage. AB - AIM: Severe neurogenic pulmonary edema (NPE) can occur in a variety of brain insults, including subarachnoid hemorrhage (SAH), and severe case of NPE can cause devastating consequences. But the literature on the treatment strategy about aneurysmal SAH with NPE is very scant. We present that SAH patients with severe NPE, who were treated first by embolization of aneurysm followed by insertion of lumbar spinal drainage, had comparatively good outcome. MATERIAL AND METHODS: We present 12 consecutive cases of aneurysmal SAH with NPE in the acute stage, which were treated by endovascular treatment between April 2002 and December 2012. We classified the patients according to the Hunt and Hess grading system as follows: grade-3 (1 patient), grade-4 (4 patients), and grade-5 (7 patients). All patients needed respiratory management, with the assistance of a ventilator, and underwent endovascular treatment for the ruptured aneurysms within 72 hours from onset. For all the patients, immediately after the endovascular treatment, we performed lumbar spinal drainage. RESULTS: The pulmonary edema disappeared rapidly after respiratory management and endovascular treatment. The outcomes were as follows: good recovery (GR; 3 patients), moderate disability (MD; 4 patients), severe disability (SD; 3 patients), and death (D; 2 patients). Five patients (42%) developed pneumonia, and we postponed extubation until recovery from pneumonia. The cause for severe disability and death was symptomatic vasospasm and primary brain damage. No patients had rebleeding from ruptured aneurysms. CONCLUSION: Endovascular treatment for ruptured aneurysm and placement of lumbar spinal drainage is an excellent treatment option for severe SAH with NPE. PMID- 27560530 TI - Biocompatibility of Plastic Clip in Neurocranium - Experimental Study on Dogs. AB - AIM: A potential advantage of the use of the plastic clips in neurosurgery is their property of causing fewer artifacts than titanium clips as assessed by computed tomography and magnetic resonance scans. The biocompatibility of plastic clips was demonstrated in the peritoneal cavity, but their behavior in the neurocranium is not known. MATERIAL AND METHODS: Twelve aggressive stray dogs designated for euthanasia were taken for this experimental study. The animals were divided into two groups. In all cases, after anesthesia, a craniotomy was performed, and after opening the dura, a proximal part titanium clip was placed on the isolated superficial Sylvian vein (a permanent Yasargil FT 746 T clip at a 90 degrees angle, while a plastic Hem-o-lok clip ML was placed on another part of the vein). The first group of animals was sacrificed on the 7 < sup > th < /sup > postoperative day and the second group on the 60 < sup > th < /sup > postoperative day. Samples of tissue around the clips were taken for a histopathological evaluation. RESULTS: The plastic clip caused a more intensive tissue reaction than the titanium clip on the 7 < sup > th < /sup > postoperative day, but there was no statistical difference. Even on the 60 < sup > th < /sup > postoperative day there was no significant difference in tissue reaction between the titanium and plastic clips. CONCLUSION: These preliminary results confirm the possibility for the use of plastic clips in neurosurgery. Before their use in human neurosurgery, further studies are needed to investigate the long-term effects of the presence of plastic clips in the neurocranium, as well as studies of the aneurysmal model. PMID- 27560531 TI - Comparison of Etanercept, Etomidate and Erythropoietin and Their Combinations in Experimentally-Induced Spinal Cord Injury. AB - AIM: The aim of this study was to compare the preventive effects of Etanercept, Etomidate, Erythropoietin and their combination in experimentally induced spinal cord trauma by clinical, histopathological, electrophysiological parameters and biochemical examination. MATERIAL AND METHODS: 85 healthy female Wistar-Albino rats were used in this study. Rats were divided 8 trauma groups that consisted of 10 rats for each, and 5 rats for the sham group. Laminectomy was performed under general anesthesia and the spinal cord was exposed with intact dura mater, and injury was created by the clip compression model. After the spinal cord injury, drugs were administered immediately intraperitoneally or subcutaneously. Except the sham group, all groups received drugs and were observed 24 or 72 hours. At the 72nd hour each group was anesthesized and somatosensorial evoked potentials (SEP) were recorded from the interarcuate ligament from the 2 vertebra proximal to the injured spinal cord and spinal cord tissue samples were taken for histopathological and biochemical evaluation. RESULTS: Etomidate groups showed a lower effect on spinal cord injury than etanercept and erythropoietin in terms of clinical, SEP and TNF-alpha. Etanercept and erythropoietin's neuroprotective effectiveness was shown alone or in combination treatments. More meaningful results were achieved with the use of erythropoietin and etanercept combination after spinal cord injury (SCI) than using erythropoietin alone. After SCI, highest Basso, Beattie, and Bresnahan (BBB) scores were achieved in the group which Etanercept and Erythropoietin applied together. CONCLUSION: The neuroprotective activity of etomidate was suspect. The neuroprotective effect of etanercept and erythropoietin after SCI was shown in individual and combined applications in this study. However, more experimental studies are needed for clinical use. PMID- 27560532 TI - Massive Skull Base Ameloblastic Carcinoma with Intracranial Extension. AB - Ameloblastic carcinoma (AC) is a rare and aggressive malignant epithelial odontogenic tumor that may arise either from the mandible (66.6%) or the maxilla (33.3%). Besides being formed de novo, the tumor can develop from a pre-existing ameloblastoma or odontogenic cyst. The clinical course of AC is typically aggressive with extensive local destruction. AC has also been reported to spread to various parts of the body through lymphatic system. Skull base location and intracranial extension of this tumor are uncommon. In this case report we present the clinical course, management and follow up of an uncommonly large AC that destructed the anterior skull base and extended into the intracranial space. PMID- 27560533 TI - Surgical Strategies for Spondylodiscitis due to Lumbar Disc Surgery. AB - AIM: Despite different surgical treatment protocols at different centers for spondylodiscitis due to lumbar surgery, there is no consensus on its surgical indications. In this study, we aimed to clarify the steps to be followed in the management and treatment of postoperative spondylodiscitis. MATERIAL AND METHODS: The data of 20 cases with postoperative spondylodiscitis were evaluated. C reactive protein (CRP) was used for diagnosis and follow-up. According to culture results of the infected material obtained from the operated cases, appropriate antibiotic treatment was initiated. In non-operated cases, parenteral empirical antibiotic treatment was implemented. Surgical treatment was planned for cases with clinical and radiological instability, abscess on imaging and those who were nonrespondent to empirical antibiotic treatment. For the cases that clinically recovered and had normal CRP levels, oral antibiotic treatment was continued after parenteral antibiotic treatment. RESULTS: Of the cases; 13 were male (65%) and 7 were femals (35%). The mean age was 56.3 years (32-74). The most prevalent complaints in referral were waist and leg pain. Except one, all cases had increased CRP levels. All patients had spondylodiscitis on magnetic resonance imaging. Seven had radiological and clinical instability and 3 had epidural abscess. The most commonly growing microorganism in culture was Staphylococcus aureus. Surgical treatment was applied to seven cases and medical treatment to 13 cases. CONCLUSION: In cases with waist pain in the postoperative period, the first potential diagnosis to be considered is spondylodiscitis. Surgical treatment should be implemented for cases resistant to empirical antibiotic treatment, with abscess on imaging, or with lumbar instability. PMID- 27560534 TI - The Effect of Ozone Therapy on Experimental Vasospasm in the Rat Femoral Artery. AB - AIM: Oxidation products following subarachnoid hemorrhage (SAH) are among the causative substances of cerebral vasospasm and poor outcome. Ozone (O3) is a gas that contains three atoms of oxygen with a cyclic structure. It has been suggested that application of low-dose ozone has an antioxidant effect and provides resistance to oxidative stress. We investigated the effect of oxygen ozone therapy on rat femoral artery vasospasm. MATERIAL AND METHODS: Twenty-four male Sprague-Dawley rats were randomly separated into vasospasm, vasospasm + ozone and control groups. The femoral artery vasospasm model was used. Rats in the vasospasm + ozone group were given 4 mL of ozone (20 MU/mL) daily for 7 days. Femoral arteries were examined by light microscopy for histological changes and morphometric analysis. Kruskal Wallis test and Mann Whitney U tests were used for the statistical analysis. The values of p < 0.01 and p < 0.05 were recognized as statistically significant. RESULTS: Ozone treatment reduced the morphometric changes as irregularity of the elastic lamina, disruption of the endothelial cells, vacuolization and hemorrhages that caused by vasospasm. The measurements of the wall thickness (p=0.003; p < 0.01) and lumen diameter (p=0.001; p < 0.01) showed statistically significant difference (p < 0.01) between the vasospasm and vasospasm+ozone groups. CONCLUSION: Ozone therapy may be useful in the treatment of post-hemorrhagic vasospasm. PMID- 27560535 TI - Outcome Assessment After Surgical Treatment of Tuberculum Sellae Meningiomas- A Preliminary Report. AB - AIM: To evaluate the endocrinological and ophthalmological results of the tuberculum sellae meningioma surgery. MATRRIAL and METHODS: A total of 18 patients diagnosed with tuberculum sellae meningioma received surgical treatment at Neurosurgery Clinic at Military Medical Institute in Warsaw from January 2010 to July 2012. This analyzed group of patients included 15 females and 3 males at a mean age of 50.5 years (ranging from 30 to 73; SD +/- 13.4). In the pre operative and post-operative periods, all patients underwent magnetic resonance imaging of the head according to a uniform protocol, eye examinations with assessment of visual acuity and field of vision, as well as endocrine tests to evaluate the hypothalamic-pituitary axis (including urine specific gravity and osmolality as well as blood cortisol, TSH, fT3, and fT4 levels). All patients underwent surgical treatment of the tumor via unilateral subfrontal craniotomy, achieving macroscopically complete tumor removal (Simpson grade II resection). RESULTS: The use of the unilateral subfrontal approach helped improve vision in 88% of the treated patients. Endocrine tests revealed no hypothalamic-pituitary axis dysfunction. The most commonly diagnosed meningiomas of the area were meningothelial (77%) and transitional (12%) meningiomas. CONCLUSION: Surgical treatment of tuberculum sellae meningiomas via the unilateral subfrontal approach is a safe technique with no significant complications. Visual improvement was observed in 88% of the patients who had received this treatment. There were no hormonal disturbances in patients operated via the subfrontal approach either prior to or after the procedure, which suggests that surgical treatment of tuberculum sellae meningiomas has no effect on pituitary endocrine function. PMID- 27560536 TI - Endoscopic Evacuation of Subdural Collections. AB - AIM: Intraoperative use of the endoscope is a hot topic in neurosurgery and it gives broader visualization of critical and hardlyreached areas. Endoscope assisted surgical approach to chronic subdural haematoma (SDH) is a minimally invasive technique and may give an expansion to the regular method of burr-hole haematoma drainage. MATERIAL AND METHODS: Endoscope-assisted haematoma drainage with mini-craniotomy was performed over a 24-month period, and prospectively collected data is reviewed. A total of 10 procedures (8 patients) were performed using the endoscopeassisted technique. Four of them were chronic SDH and six were subacute SDH. RESULTS: Procedures were extended 20 minutes in average because of endoscopic intervention. There was no extra-morbidity through the study as a consequence of endoscopic assessment. CONCLUSION: Endoscope-assisted techniques can make the operation safe in selected circumstances with improved intraoperative visualization. It may likewise take into consideration the identification and destruction of neo-membranes, septums and solid clots. In addition, the source of bleeding can be easily coagulated. The endoscope-assisted techniques, with all of these features, can alter the pre- and intra-operative decision-making for selected patients. PMID- 27560537 TI - Effects of Ozone on Spinal Cord Recovery via the Wnt/ Β-Catenin Pathway Following Spinal Cord Injury in Rats. AB - AIM: At the cellular level, spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the spinal cord but may also contribute to its repair. Besides intracellular antioxydant increase after exactly estimated oxidative stress; oxygen formation and transport is also advanced by ozone. The Wnt family of proteins contributes to the development of the nervous system, influencing cell proliferation. In the present study we evaluated the effect of ozone on spinal cord injury in rats. MATERIAL AND METHODS: Twenty-one male Sprague-Dawley rats were used. The rats were randomly allocated into three groups (control, trauma and trauma+ozone). SCI was inflicted using Allen"s spinal cord trauma method. The study was performed to determine the effects of ozone therapy on rats with SCI in terms of locomotor strength clinically and neuronal injury, white matter cavitation, edema, number of blood vessels, and expression of beta-catenin immunohistochemically. RESULTS: Comparison of the locomotor strength scores revealed a significant improvement on day 7 in trauma+ozone group. The groups were compared with regard to edema, neuronal injury, and white matter cavitation. Average beta-catenin levels were significantly different between the control group (68.11 +/- 0.43), trauma+ozone group (37.96 +/- 2.16), and trauma group (25.46 +/- 1.07) (F = 1677.74, df = 2, p < 0.0005). CONCLUSION: The results of this study indicated that ozone therapy accelerates the healing process, increases vascularity, and reduces neuronal damage in rodents, suggesting that ozone therapy may be an adjuvant treatment in patients with SCI. PMID- 27560538 TI - Transcription factor PRO1 targets genes encoding conserved components of fungal developmental signaling pathways. AB - The filamentous fungus Sordaria macrospora is a model system to study multicellular development during fruiting body formation. Previously, we demonstrated that this major process in the sexual life cycle is controlled by the Zn(II)2 Cys6 zinc cluster transcription factor PRO1. Here, we further investigated the genome-wide regulatory network controlled by PRO1 by employing chromatin immunoprecipitation combined with next-generation sequencing (ChIP-seq) to identify binding sites for PRO1. We identified several target regions that occur in the promoter regions of genes encoding components of diverse signaling pathways. Furthermore, we identified a conserved DNA-binding motif that is bound specifically by PRO1 in vitro. In addition, PRO1 controls in vivo the expression of a DsRed reporter gene under the control of the esdC target gene promoter. Our ChIP-seq data suggest that PRO1 also controls target genes previously shown to be involved in regulating the pathways controlling cell wall integrity, NADPH oxidase and pheromone signaling. Our data point to PRO1 acting as a master regulator of genes for signaling components that comprise a developmental cascade controlling fruiting body formation. PMID- 27560539 TI - Constructing Well-Ordered CdTe/TiO2 Core/Shell Nanowire Arrays for Solar Energy Conversion. AB - Well-ordered CdTe/TiO2 heteronanostructure arrays are fabricated via a convenient anodic aluminum oxide template-directed approach and applied to photoelectrochemistry and solar energy devices. Both the CdTe and TiO2 present a decent crystalline quality. In comparison to the photoanode with only TiO2 nanotube array, the CdTe/TiO2 heteronanostructure electrodes possess a dramatic performance improvement. PMID- 27560540 TI - Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men. AB - In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues. PMID- 27560541 TI - Canadian physical activity guidelines for adults: are Canadians aware? AB - The present study evaluated awareness of the Canadian Society for Exercise Physiology's 2011 Canadian Physical Activity Guidelines for Adults and assessed correlates. Reported awareness of the physical activity (PA) guidelines was 12.9% (204/1586) of the total sample surveyed. More than half (55%) self-reported meeting PA guidelines of >= 150 min of moderate to vigorous PA per week. Awareness of PA guidelines was significantly related to participants' level of PA (chi(2) (1) = 30.63, p < 0.001, phi = -0.14), but not to any demographic variables. PMID- 27560542 TI - Intradomain Allosteric Network Modulates Calcium Affinity of the C-Type Lectin Receptor Langerin. AB - Antigen uptake and processing by innate immune cells is crucial to initiate the immune response. Therein, the endocytic C-type lectin receptors serve as pattern recognition receptors, detecting pathogens by their glycan structures. Herein, we studied the carbohydrate recognition domain of Langerin, a C-type lectin receptor involved in the host defense against viruses such as HIV and influenza as well as bacteria and fungi. Using a combination of nuclear magnetic resonance and molecular dynamics simulations, we unraveled the molecular determinants underlying cargo capture and release encoded in the receptor architecture. Our findings revealed receptor dynamics over several time scales associated with binding and release of the essential cofactor Ca(2+) controlled by the coupled motions of two loops. Applying mutual information theory and site-directed mutagenesis, we identified an allosteric intradomain network that modulates the Ca(2+) affinity depending on the pH, thereby promoting fast ligand release. PMID- 27560543 TI - The protective effect of job satisfaction in health, happiness, well-being and self-esteem. AB - The purpose of this article is to analyze the possible effects of job satisfaction on mental and physical health, happiness, subjective well-being and self-esteem. A total of 971 Portuguese-speaking adults participated in this study. Most participants reported high rates of satisfaction with their colleagues, the nature of their work and leadership, while reporting dissatisfaction with regard to salaries and promotions. Results indicated the existence of the protector effect of job satisfaction for health, happiness, subjective well-being and self-esteem, in addition to reinforcing the importance of maintaining a positive evaluation of one's work. As a practical implication, the results may suggest that the effects of personnel management policies which emphasize job satisfaction could potentially lead to improvements in levels of health, happiness, subjective well-being and workers' self-esteem, all of which are factors that can potentially improve organizational performance. The study also considered its limitations and the possibility for future investigation. PMID- 27560544 TI - A supervised learning framework for pancreatic islet segmentation with multi scale color-texture features and rolling guidance filters. AB - Islet cell quantification and function is important for developing novel therapeutic interventions for diabetes. Existing methods of pancreatic islet segmentation in histopathological images depend strongly on cell/nuclei detection, and thus are limited due to a wide variance in the appearance of pancreatic islets. In this paper, we propose a supervised learning pipeline to segment pancreatic islets in histopathological images, which does not require cell detection. The proposed framework firstly partitions images into superpixels, and then extracts multi-scale color-texture features from each superpixel and processes these features using rolling guidance filters, in order to simultaneously reduce inter-class ambiguity and intra-class variation. Finally, a linear support vector machine (SVM) is trained and applied to segment the testing images. A total of 23 hematoxylin-and-eosin-stained histopathological images with pancreatic islets are used for verifying the framework. With an average accuracy of 95%, training time of 20 min and testing time of 1 min per image, the proposed framework outperforms existing approaches with better segmentation performance and lower computational cost. (c) 2016 International Society for Advancement of Cytometry. PMID- 27560545 TI - Organic Electronics: An El Dorado in the Quest of New Photocatalysts for Polymerization Reactions. AB - Photoinitiated polymerization has been the subject of continued research efforts due to the numerous applications in which this polymerization technique is involved (coatings, inks, adhesives, optoelectronic, laser imaging, stereolithography, nanotechnology, etc.). More recently, photopolymerization has received renewed interest due to the emergence of 3D-printing technologies. However, despite current academic and industrial interest in photopolymerization methodologies, a major limitation lies in the slow rates of photopolymerization. The development of new photoinitiating systems aimed at addressing this limitation is an active area of research. Photopolymerization occurs through the exposure of a curable formulation to light, generating radical and/or cationic species to initiate polymerization. At present, photopolymerization is facing numerous challenges related to safety, economic and ecological concerns. Furthermore, practical considerations such as the curing depth and the competition for light absorption between the chromophores and other species in the formulation are key parameters drastically affecting the photopolymerization process. To address these issues, photoinitiating systems operating under low intensity visible light irradiation, in the absence of solvents are highly sought after. In this context, the use of photoredox catalysis can be highly advantageous; that is, photoredox catalysts can provide high reactivities with low catalyst loading, permitting access to high performance photoinitiating systems. However, to act as efficient photoredox catalysts, specific criteria have to be fulfilled. A strong absorption over the visible range, an ability to easily oxidize or reduce as well as sufficient photochemical stability are basic prerequisites to make these molecules desirable candidates for photoredox catalysis. Considering the similarity of requirements between organic electronics and photopolymerization, numerous materials initially designed for applications in organic electronics have been revisited in the context of photopolymerization. Organic electronics is a branch of electronics and materials science focusing on the development of semiconductors devoted to three main research fields; organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs), and organic solar cells (OSCs). The contribution of organic electronics to the field of electronics is important as it paves the way toward cheaper, lighter, and more energy efficient devices. In the present context of photopolymerization, materials that were investigated as photocatalysts were indifferently organic semiconductors used for transistors, charge-transport materials, and light emitting materials used in electroluminescent devices or conjugated polymers and small molecule dyes for solar cells. In this Account, we summarize our latest developments in elaborating on photocatalytic systems based on these new classes of compounds. Through an in-depth understanding of the parameters governing their reactivities and our efforts to incorporate these materials into photoinitiating systems, we provide new knowledge and a valuable insight for future prospects. PMID- 27560546 TI - Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/beta-catenin signaling pathway. AB - With the development of functional genomics studies, a mass of long non-coding RNAs (LncRNA) were discovered from the human genome. Long non-coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA-binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma-associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/beta-catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1-beta-catenin-WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA-directed diagnostic and therapeutic strategy for this fatal disease. PMID- 27560548 TI - Evolution of the Hypothalamic-Pituitary-Gonadal Axis Regulation in Vertebrates Revealed by Knockout Medaka. AB - Reproduction is essential for life, but its regulatory mechanism is diverse. The analysis of this diversity should lead us to understand the evolutionary process of the regulation of reproduction. In mammals, the hypothalamic-pituitary-gonadal axis plays an essential role in such regulation, and each component, hypothalamic GnRH, and pituitary gonadotropins, LH, and FSH, is indispensable. However, the common principle of the hypothalamic-pituitary-gonadal axis regulation among vertebrates remains unclear. Here, we used a teleost medaka, which is phylogenetically distant from mammals, and analyzed phenotypes of gene knockouts (KOs) for GnRH, LH, and FSH. We showed that LH release, which we previously showed to be directly triggered by GnRH, is essential for ovulation in females, because KO medaka of GnRH and LH were anovulatory in spite of the full follicular growth and normal gonadosomatic index, and spawning could be induced by a medaka LH receptor agonist. On the other hand, we showed that FSH is necessary for the folliculogenesis, because the follicular growth of FSH KO medaka was halted at the previtellogenic stage, but FSH release does not necessarily require GnRH. By comparing these results with the previous studies in mammals that both GnRH and LH are necessary for folliculogenesis, we propose a hypothesis as follows. During evolution, LH was originally specialized for ovulation, and regulation of folliculogenesis by GnRH-LH (pulsatile release) was newly acquired in mammals, which enabled fine tuning of reproduction through hypothalamus. PMID- 27560547 TI - Adverse Reproductive and Developmental Health Outcomes Following Prenatal Exposure to a Hydraulic Fracturing Chemical Mixture in Female C57Bl/6 Mice. AB - Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 MUg/kg.d, flutamide at 50 mg/kg.d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies. PMID- 27560549 TI - Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study. AB - Importance: The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles. Objective: To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial. Design, Setting, and Participants: The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors. Main Outcomes and Measures: Total number of docetaxel cycles delivered as an independent factor for OS. Results: Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001). Conclusions and Relevance: These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted. PMID- 27560550 TI - The assessment of the robustness of microRNAs from oral cytological scrapings. AB - BACKGROUND: Sampling of suspect oral lesions in the general dental clinic may increase early carcinoma detection thus oral cancer survival rates. One means of lesion sampling that is an alternative to incisional biopsy is cytological scraping. MicroRNA alterations are also being explored as a means of diagnosing carcinoma as an alternative to histopathology. METHODS: We obtained cytological scrapings using 10 strokes ('light') or 40 strokes ('heavy') from the buccal mucosa of one healthy subject using a dermatological curette. MicroRNA was isolated from oral cytological scrapings immediately, or the scrapings were stored in buffer or RNA later, at 4 degrees C, room temperature or 36 degrees C, from 1 to 7 days prior to RNA isolation. All scrape comparisons and test conditions were conducted in triplicate. MicroRNAs were measured using qRT-PCR. RESULTS: MicroRNAs can be obtained from cytological scrapings independent of the number of strokes and can be measured using qRT-PCR after storage under all conditions tested. CONCLUSION: MicroRNAs are robust to a wide range of storage conditions that bodes well for use of cytological scrapings to be of use in a clinical setting as a chair side sampling method for suspect oral lesions. PMID- 27560551 TI - Sulfatase-2: a prognostic biomarker and candidate therapeutic target in patients with pancreatic ductal adenocarcinoma. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer death in the UK. Its poor prognosis is attributed to late detection and limited therapeutic options. Expression of SULF2, an endosulfatase that modulates heparan sulfate proteoglycan 6-O-sulfation and is reportedly tumourigenic in different types of cancer, was investigated. METHODS: SULF2 expression was determined immunohistochemically in archival surgical resection tissue sections from 93 patients with a confirmed histological diagnosis of PDAC between 2002 and 2008 followed for a median of 9 years. Relationships with clinico-pathological parameters and patient survival were explored. RESULTS: The majority of PDACs showed positive SULF2 staining in tumour cells and intratumoural or tumour-adjacent stroma. Greater than 25% SULF2-positive tumour cells was present in 60% of cancers and correlated with tumour stage (P=0.002) and perineural invasion (P=0.024). SULF2 intensity was scored moderate or strong in 81% of cancers and positively correlated with vascular invasion (P=0.015). High SULF2 expression, defined as >50% SULF2-positive tumour cells and strong SULF2 staining, was associated with shorter time to radiological progression (P=0.018, HR 1.98, CI 1.13-3.47). Similarly, by multivariate analysis, high SULF2 expression was independently associated with poorer survival (P=0.004, HR 2.10, CI 1.26-3.54), with a median survival of 11 months vs 21 months for lower PDAC SULF2. CONCLUSIONS: Elevated SULF2 in PDAC was associated with advanced tumour stage, vascular invasion, shorter interval to radiological progression and shorter overall survival. SULF2 may have roles as a prognostic biomarker and as a therapeutic target for patients with PDAC. PMID- 27560552 TI - Establishment and molecular characterisation of seven novel soft-tissue sarcoma cell lines. AB - BACKGROUND: Soft-tissue sarcomas (STS) are a diverse group of malignancies that remain a diagnostic and therapeutic challenge. Relatively few reliable cell lines currently exist. Rapidly developing technology for genomic profiling with emerging insights into candidate functional (driver) aberrations raises the need for more models for in vitro functional validation of molecular targets. METHODS: Primary cell culture was performed on STS tumours utilising a differential attachment approach. Cell lines were characterised by morphology, immunocytochemistry, proliferation assays, short tandem repeat (STR) and microarray-based genomic copy number profiling. RESULTS: Of 47 STS cases of various subtypes, half formed adherent monolayers. Seven formed self-immortalised cell lines, including three undifferentiated pleomorphic sarcomas, two dedifferentiated liposarcomas (one of which had received radiotherapy), a leiomyosarcoma and a myxofibrosarcoma. Two morphologically distinct yet genetically identical variants were established in separate cultures for the latter two tumours. All cell lines demonstrated genomic and phenotypic features that not only confirm their malignant characteristics but also confirm retention of DNA copy number aberrations present in their parent tumours that likely include drivers. CONCLUSIONS: These primary cell lines are much-needed additions to the number of reliable cell lines of STS with complex genomics available for initial functional validation of candidate molecular targets. PMID- 27560553 TI - MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient derived xenograft model. AB - BACKGROUND: Renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKI) typically respond initially, but usually develop resistance to therapy. We utilised transcriptome analysis to identify gene expression changes during development of sunitinib resistance in a RCC patient-derived xenograft (PDX) model. METHODS: RCC tumours were harvested during pre-treatment, response and escape phases. Direct anti-proliferative effects of sunitinib plus MEK inhibitor were assessed. Activation status (phosphorylation) of MEK1/2 and ERK1/2 was determined, myeloid-derived suppressor cells (MDSC) sub-fractions were quantitated and G-CSF was measured by ELISA. RESULTS: During the response phase, tumours exhibited 91% reduction in volume, characterised by decreased expression of cell survival genes. After 4-week treatment, tumours developed resistance to sunitinib, associated with increased expression of pro-angiogenic and cell survival genes. During tumour escape, cellular movement, inflammatory response and immune cell trafficking genes were induced, along with intra-tumoural accumulation of MDSC. In this PDX model, either continuous treatment with sunitinib plus MEK inhibitor PD-0325901, or switching from sunitinib to PD 0325901 was effective. The combination of PD-0325901 with TKI suppressed intra tumoural phospho-MEK1/2, phospho-ERK1/2 and MDSC. CONCLUSIONS: Continuous treatment with sunitinib alone did not maintain anti-tumour response; addition of MEK inhibitor abrogated resistance, leading to improved anti-tumour efficacy. PMID- 27560556 TI - Layer-by-Layer Assembly of Fluorine-Free Polyelectrolyte-Surfactant Complexes for the Fabrication of Self-Healing Superhydrophobic Films. AB - Fluorine-free self-healing superhydrophobic films are of significance for practical applications because of their extended service life and cost-effective and eco-friendly preparation process. In this study, we report the fabrication of fluorine-free self-healing superhydrophobic films by layer-by-layer (LbL) assembly of poly(sodium 4-styrenesulfonate) (PSS)-1-octadecylamine (ODA) complexes (PSS-ODA) and poly(allylamine hydrochloride) (PAH)-sodium dodecyl sulfonate (SDS) (PAH-SDS) complexes. The wettability of the LbL-assembled PSS ODA/PAH-SDS films depends on the film structure and can be tailored by changing the NaCl concentration in aqueous dispersions of PSS-ODA complexes and the number of film deposition cycles. The freshly prepared PSS-ODA/PAH-SDS film with micro- and nanoscaled hierarchical structures is hydrophilic and gradually changes to superhydrophobic in air because the polyelectrolyte-complexed ODA and SDS surfactants tend to migrate to the film surface to cover the film with hydrophobic alkyl chains to lower its surface energy. The large amount of ODA and SDS surfactants loaded in the superhydrophobic PSS-ODA/PAH-SDS films and the autonomic migration of these surfactants to the film surface endow the resultant superhydrophobic films with an excellent self-healing ability to restore the damaged superhydrophobicity. The self-healing superhydrophobic PSS-ODA/PAH-SDS films are mechanically robust and can be deposited on various flat and nonflat substrates. The LbL assembly of oppositely charged polyelectrolyte-surfactant complexes provides a new way for the fabrication of fluorine-free self-healing superhydrophobic films with satisfactory mechanical stability, enhanced reliability, and extended service life. PMID- 27560555 TI - A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics. AB - BACKGROUND: Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood based biomarker series using a single assay, suitable for CRC detection, prognostication and staging. METHODS: Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated. RESULTS: A diagnostic signature for CRC with remarkable multivariate performance (R(2)Y=0.46, Q(2)Y=0.39) was constructed, and then validated (sensitivity 85%; specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87-0.96). Adenomas were also detectable (R(2)Y=0.35, Q(2)Y=0.26, internal AUROC=0.81, 95% CI, 0.70-0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage. CONCLUSIONS: Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers. PMID- 27560557 TI - Prostaglandin versus mechanical dilation and the effect of maternal obesity on failure to achieve active labor: a cohort study. AB - PURPOSE: Assess the impact of obesity on successful cervical ripening with mechanical versus prostaglandin ripening. MATERIALS AND METHODS: We compared obese to non-obese women in an analysis stratified by induction method, prostaglandin versus mechanical. Misoprostol dosing was the same for obese and non-obese women. Pitocin was titrated to effect. Our primary outcome was failure to achieve active labor. Secondary outcomes included overall cesarean delivery rate, doses of misoprostol used and need for protocol deviation. RESULTS: Obese women had a higher cesarean delivery rate with misoprostol (35% versus 26%, p = 0.03) but not with mechanical ripening (31% versus 29%, p = 0.69). Obesity was associated with a higher rate of failure to achieve active labor in women undergoing prostaglandin ripening with misoprostol (24 versus 15%, p = 0.01) but not in women undergoing mechanical ripening (19 versus 15%, p = 0.55). After controlling for confounding variables, obese women who underwent cervical ripening with misoprostol had a higher rate of failure to achieve active labor, aOR 1.29 (95%CI: 1.00-1.67), which was not seen with mechanical ripening, aOR 1.09 (95%CI: 0.69-1.73). CONCLUSION: Obese women receiving the same dose of misoprostol as non-obese women have higher rates of failure to achieve active labor, an effect not seen with mechanical ripening. PMID- 27560554 TI - Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective: results from a prospective intervention study. AB - BACKGROUND: The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long. METHODS: We evaluated timely diagnosis and health care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ?50 years with macroscopic haematuria. The control group comprised 101 patients diagnosed with bladder cancer in the same catchment area with macroscopic haematuria who underwent regular diagnostic process. RESULTS: In all 275 patients who called 'the Red Phone' hotline were investigated, and 47 of them (17%) were diagnosed with cancer and 36 of those had bladder cancer. Median time from patient-reported haematuria to diagnosis was 29 (interquartile range (IQR) 14 104) days and 50 (IQR 27-165) days in the intervention and the control group, respectively (P=0.03). The median health-care costs were lower in the intervention group (655 (IQR 655-655) EUR) than in the control group (767 (IQR 490-1096) EUR) (P=0.002). CONCLUSIONS: Direct access to urologic expertise and fast-track diagnostics is motivated for patients with macroscopic haematuria to reduce diagnostic intervals and lower health-care expenditures. PMID- 27560598 TI - Guinea Worm (Dracunculus medinensis) Infection in a Wild-Caught Frog, Chad. AB - A third-stage (infective) larva of Dracunculus medinensis, the causative agent of Guinea worm disease, was recovered from a wild-caught Phrynobatrachus francisci frog in Chad. Although green frogs (Lithobates clamitans) have been experimentally infected with D. medinensis worms, our findings prove that frogs can serve as natural paratenic hosts. PMID- 27560599 TI - Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research. AB - BACKGROUND: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). METHODS/DESIGN: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. RESULTS: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. CONCLUSION: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types. PMID- 27560600 TI - Severe maternal morbidity: screening and review. AB - This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review. PMID- 27560603 TI - Dopant-Free Donor (D)-pi-D-pi-D Conjugated Hole-Transport Materials for Efficient and Stable Perovskite Solar Cells. AB - Three novel hole-transporting materials (HTMs) using the 4-methoxytriphenylamine (MeOTPA) core were designed and synthesized. The energy levels of the HTMs were tuned to match the perovskite energy levels by introducing symmetrical electron donating groups linked with olefinic bonds as the pi bridge. The methylammonium lead triiodide (MAPbI3 ) perovskite solar cells based on the new HTM Z34 (see main text for structure) exhibited a remarkable overall power conversion efficiency (PCE) of 16.1 % without any dopants or additives, which is comparable to 16.7 % obtained by a p-doped 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino) 9,9'-spirobifluorene (spiro-OMeTAD)-based device fabricated under the same conditions. Importantly, the devices based on the three new HTMs show relatively improved stability compared to devices based on spiro-OMeTAD when aged under ambient air containing 30 % relative humidity in the dark. PMID- 27560602 TI - Atractylodes lactone compounds inhibit platelet activation. AB - Platelets play a crucial role in the development and progression of atherosclerosis-thrombosis and, therefore, antiplatelet drugs are widely used in the treatment of coronary artery disease. Moreover, advances in understanding the biological functions of natural plant products can provide new pharmacological strategies aimed at promoting cardiovascular health. Atractylenolide I (ATL-1), ATL-2, and ATL-3 are the major bioactive components of a Qi tonifying medicinal herb Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala), which is commonly used in traditional Chinese medicine (TCM). These components possess well-documented anti-inflammatory and anticancer activities, but their effects on platelet activation are still unknown. In this study, the effects of ATL on platelet function in vitro and in vivo were investigated, and the underlying mechanism was explored. We found that ATL-2 and ATL-3 but not ATL-1 diminished agonist-induced platelet aggregation and diminished adenosine triphosphate (ATP) release from dense granules. The levels of phospho-Akt (Ser473) and phospho-p38 MAPK were downregulated in the presence of ATL-2 and ATL-3. We also found that ATL-2 and ATL-3 have a similar inhibitory effect on platelet activation as acetylsalicylic acid in response to agonists. Furthermore, ATL-2 and ATL-3 diminished the spreading of human platelets on immobilized fibrinogen (Fg), delayed clot retraction in platelet-depleted plasma containing human platelets, extended first occlusion time in a mouse model of ferric chloride (FeCl3)-induced carotid arterial thrombosis, and prolonged the bleeding time. These observations suggest that ATL-2 and ATL-3 are potential candidate therapeutic drugs for the prevention of thrombosis. PMID- 27560601 TI - Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license. AB - The capacity of the olfactory epithelium (OE) for lifelong neurogenesis and regeneration depends on the persistence of neurocompetent stem cells, which self renew as well as generating all of the cell types found within the nasal epithelium. This Review focuses on the types of stem and progenitor cells in the epithelium and their regulation. Both horizontal basal cells (HBCs) and some among the population of globose basal cells (GBCs) are stem cells, but the two types plays vastly different roles. The GBC population includes the basal cells that proliferate in the uninjured OE and is heterogeneous with respect to transcription factor expression. From upstream in the hierarchy to downstream, GBCs encompass 1) Sox2+ /Pax6+ stem-like cells that are totipotent and self-renew over the long term, 2) Ascl1+ transit-amplifying progenitors with a limited capacity for expansive proliferation, and 3) Neurog1+ /NeuroD1+ immediate precursor cells that make neurons directly. In contrast, the normally quiescent HBCs are activated to multipotency and proliferate when sustentacular cells are killed, but not when only OSNs die, indicating that HBCs are reserve stem cells that respond to severe epithelial injury. The master regulator of HBC activation is the DeltaN isoform of the transcription factor p63; eliminating DeltaNp63 unleashes HBC multipotency. Notch signaling, via Jagged1 ligand on Sus cells and Notch1 and Notch2 receptors on HBCs, is likely to play a major role in setting the level of p63 expression. Thus, DeltaNp63 becomes a potential therapeutic target for reversing the neurogenic exhaustion characteristic of the aged OE. J. Comp. Neurol. 525:1034-1054, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27560604 TI - Photochemical Tagging for Quantitation of Unsaturated Fatty Acids by Mass Spectrometry. AB - Fatty acid (FA) profiling provides phenotypic information and is increasingly used in a broad range of biological and biomedical studies. Quantitation of unsaturated FAs with confident carbon-carbon double bond (C?C) location assignment is both sample and time consuming using traditional gas chromatography mass spectrometry analysis. In this study, we developed a rapid, sensitive, and quantitative method for profiling unsaturated FAs without using chromatographic separations. This method was based on a combination of in-solution photochemical tagging of a C?C in FAs and a subsequent gas-phase detagging via tandem (neutral loss scan) mass spectrometry. It enabled quantitation of unsaturated FAs from various biological samples (blood, plasma, and cell lines). More importantly, quantitative information on FA C?C location isomers, which was traditionally overlooked, could now be obtained and applied to studying FA changes between normal and cancerous human prostate cells. PMID- 27560605 TI - Evaluation of the Risk of Postoperative Infection in Adjustable Suture Strabismus Surgery. PMID- 27560606 TI - Comparison of methods for the prediction of human clearance from hepatocyte intrinsic clearance for a set of reference compounds and an external evaluation set. AB - 1. We compared direct scaling, regression model equation and the so-called "Poulin et al." methods to scale clearance (CL) from in vitro intrinsic clearance (CLint) measured in human hepatocytes using two sets of compounds. One reference set comprised of 20 compounds with known elimination pathways and one external evaluation set based on 17 compounds development in Merck (MS). 2. A 90% prospective confidence interval was calculated using the reference set. This interval was found relevant for the regression equation method. The three outliers identified were justified on the basis of their elimination mechanism. 3. The direct scaling method showed a systematic underestimation of clearance in both the reference and evaluation sets. The "Poulin et al." and the regression equation methods showed no obvious bias in either the reference or evaluation sets. 4. The regression model equation was slightly superior to the "Poulin et al." method in the reference set and showed a better absolute average fold error (AAFE) of value 1.3 compared to 1.6. A larger difference was observed in the evaluation set were the regression method and "Poulin et al." resulted in an AAFE of 1.7 and 2.6, respectively (removing the three compounds with known issues mentioned above). A similar pattern was observed for the correlation coefficient. Based on these data we suggest the regression equation method combined with a prospective confidence interval as the first choice for the extrapolation of human in vivo hepatic metabolic clearance from in vitro systems. PMID- 27560607 TI - Laser-Direct Writing of Silver Metal Electrodes on Transparent Flexible Substrates with High-Bonding Strength. AB - We demonstrate a novel approach to rapidly fabricate conductive silver electrodes on transparent flexible substrates with high-bonding strength by laser-direct writing. A new type of silver ink composed of silver nitrate, sodium citrate, and polyvinylpyrrolidone (PVP) was prepared in this work. The role of PVP was elucidated for improving the quality of silver electrodes. Silver nanoparticles and sintered microstructures were simultaneously synthesized and patterned on a substrate using a focused 405 nm continuous wave laser. The writing was completed through the transparent flexible substrate with a programmed 2D scanning sample stage. Silver electrodes fabricated by this approach exhibit a remarkable bonding strength, which can withstand an adhesive tape test at least 50 times. After a 1500 time bending test, the resistance only increased 5.2%. With laser-induced in situ synthesis, sintering, and simultaneous patterning of silver nanoparticles, this technology is promising for the facile fabrication of conducting electronic devices on flexible substrates. PMID- 27560608 TI - Vocational interests assessed at the end of high school predict life outcomes assessed 10 years later over and above IQ and Big Five personality traits. AB - Vocational interests are important aspects of personality that reflect individual differences in motives, goals, and personal strivings. It is therefore plausible that these characteristics have an impact on individuals' lives not only in terms of vocational outcomes, but also beyond the vocational domain. Yet the effects of vocational interests on various life outcomes have rarely been investigated. Using Holland's RIASEC taxonomy (Holland, 1997), which groups vocational interests into 6 broad domains, the present study examined whether vocational interests are significant predictors of life outcomes that show incremental validity over and above the Big Five personality traits. For this purpose, a cohort of German high school students (N = 3,023) was tracked over a period of 10 years after graduating from school. Linear and logistic regression analyses were used to examine the predictive validity of RIASEC interests and Big Five personality traits. Nine outcomes from the domains of work, relationships, and health were investigated. The results indicate that vocational interests are important predictors of life outcomes that show incremental validity over the Big Five personality traits. Vocational interests were significant predictors of 7 of the 9 investigated outcomes: full-time employment, gross income, unemployment, being married, having children, never having had a relationship, and perceived health status. For work and relationship outcomes, vocational interests were even stronger predictors than the Big Five personality traits. For health-related outcomes, the results favored the personality traits. Effects were similar across gender for all outcomes-except 2 relationship outcomes. Possible explanations for these effects are discussed. (PsycINFO Database Record PMID- 27560609 TI - Narcissism and romantic relationships: The differential impact of narcissistic admiration and rivalry. AB - Narcissism is known to be related to romantic success in short-term contexts (dating, early stage relationships) but also to problems in long-term committed relationships. We propose that these diverging romantic outcomes of narcissism can be explained by differential associations with agentic versus antagonistic dimensions of grandiose narcissism: Narcissistic Admiration and Rivalry. Both dimensions serve the central narcissistic goal of gaining and maintaining a grandiose self-view, but do so by different processes: Admiration is characterized by the tendency to promote the positivity of one's self-view by seeking social admiration (assertive self-enhancement). Rivalry is characterized by the tendency to protect oneself from a negative self-view by derogating others (antagonistic self-protection). Across 7 studies (total N = 3,560) using diverse measures and methodological approaches (self-, peer, and partner reports, as well as interpersonal perception measures in video-based studies, face-to-face laboratory encounters, and online surveys), we show that the short-term romantic appeal associated with narcissism is primarily attributable to the dimension of Admiration, whereas the long-term romantic problems associated with narcissism are primarily attributable to the dimension of Rivalry. These results highlight the utility of a 2-dimensional reconceptualization of grandiose narcissism for explaining its heterogeneous romantic outcomes. The findings further underscore the idea that different facets of personality traits might impact different aspects of romantic relationship quality, depending on the stage of the relationship. Such a more nuanced view increases the predictive validity of personality traits in social relationship research. (PsycINFO Database Record PMID- 27560611 TI - Is group membership necessary for understanding generalized prejudice? A re evaluation of why prejudices are interrelated. AB - Many scholars have proposed that people who reject one outgroup tend to reject other outgroups. Studies examining a latent factor behind different prejudices (e.g., toward ethnic and sexual minorities) have referred to this as generalized prejudice. Such research has also documented robust relations between latent prejudice factors and basic personality traits. However, targets of generalized prejudice tend to be lower in power and status and thus it remains an open question as to whether generalized prejudice, as traditionally studied, is about devaluing outgroups or devaluing marginalized groups. We present 7 studies, including experiments and national probability samples (N = 9,907 and 4,037) assessing the importance of outgroup devaluation, versus status- or power based devaluations, for understanding the nature of generalized prejudice, and its links to personality. Results show that (a) personality variables do not predict ingroup/outgroup biases in settings where power and status differences are absent, (b) women and overweight people who score high on generalized prejudice devalue their own groups, and (c) personality variables are far more predictive of prejudice toward low-compared with high-status targets. Together, these findings suggest that the personality explanation of prejudice including the generalized prejudice concept is not about ingroups versus outgroups per se, but rather about devaluing marginalized groups. (PsycINFO Database Record PMID- 27560612 TI - "Decision sidestepping: How the motivation for closure prompts individuals to bypass decision making": Correction to Otto et al. (2016). AB - Reports an error in "Decision sidestepping: How the motivation for closure prompts individuals to bypass decision making" by Ashley S. Otto, Joshua J. Clarkson and Frank R. Kardes (Journal of Personality and Social Psychology, 2016[Jul], Vol 111[1], 1-16). In the article, the main heading for Experiment 3 was missing due to a production error, and the first sentence of the first paragraph of Experiment 3 should begin as follows: Experiment 2 offered support for the hypothesis that those seeking closure engage in decision sidestepping to reduce the bothersome nature of decision making. (The following abstract of the original article appeared in record 2016-30159-001.) We all too often have to make decisions-from the mundane (e.g., what to eat for breakfast) to the complex (e.g., what to buy a loved one)-and yet there exists a multitude of strategies that allows us to make a decision. This work focuses on a subset of decision strategies that allows individuals to make decisions by bypassing the decision making process-a phenomenon we term decision sidestepping. Critical to the present manuscript, however, we contend that decision sidestepping stems from the motivation to achieve closure. We link this proposition back to the fundamental nature of closure and how those seeking closure are highly bothered by decision making. As such, we argue that the motivation to achieve closure prompts a reliance on sidestepping strategies (e.g., default bias, choice delegation, status quo bias, inaction inertia, option fixation) to reduce the bothersome nature of decision making. In support of this framework, five experiments demonstrate that (a) those seeking closure are more likely to engage in decision sidestepping, (b) the effect of closure on sidestepping stems from the bothersome nature of decision making, and (c) the reliance on sidestepping results in downstream consequences for subsequent choice. Taken together, these findings offer unique insight into the cognitive motivations stimulating a reliance on decision sidestepping and thus a novel framework by which to understand how individuals make decisions while bypassing the decision-making process. PMID- 27560610 TI - Daily goal progress is facilitated by spousal support and promotes psychological, physical, and relational well-being throughout adulthood. AB - In 2 daily diary studies, we tested the consequences and precursors of daily goal progress throughout the adult life span. Attachment theory posits that exploration-including the pursuit of autonomous goals-promotes well-being across the life span and is facilitated by support from close others. For both young adult newlyweds (Study 1) and married couples in late adulthood (Study 2), daily independent goal progress predicted same-day and next-day improvements in psychological, physical, and relational well-being. Specifically, when participants made more progress on their goals than usual on one day, they reported increases in positive affect, sleep quality, and relationship quality, and decreased physical symptoms, the following day (as well as concurrently). Additionally, spousal support (i.e., availability, encouragement, and noninterference) enabled same-day and next-day goal progress. Mediational analyses showed indirect links between spousal support and well-being through goal progress. Some effects were moderated by attachment orientation in the newlywed sample; individuals with greater insecure attachment benefited most from goal progress, and spousal support enabled goal progress most strongly for individuals with less anxious attachment. Overall, these results support and extend attachment theoretical propositions regarding the importance of the exploration system across the adult life span. They contribute to existing literature by demonstrating wide-ranging consequences of successful exploration for well-being and by providing evidence for the importance of both exploration and support for exploration into late adulthood. (PsycINFO Database Record PMID- 27560613 TI - Canadian Association of Cardiovascular Prevention and Rehabilitation (Association Canadienne de Prevention et de Readaptation Cardiovasculaires) Annual Meeting and Scientific Abstracts: October 22-23, 2016, Palais des congres de Montreal, Montreal, Quebec, Canada. PMID- 27560615 TI - Synthesis of a Bent 2-Silaallene with a Perturbed Electronic Structure from a Cyclic Alkyl(amino) Carbene-Diiodosilylene. AB - The cyclic alkyl(amino) carbene (cAAC) 1 reacted with SiI4 in toluene, affording the cAAC-silicon tetraiodide complex [(cAACMe)SiI4] (2, cAACMe = :C(CH2)(CMe2)2NAr, Ar = 2,6-iPr2C6H3). It further reacted with two equivalents of KC8 in toluene at room temperature to afford the first cAAC-diiodosilylene [(cAACMe)SiI2] (3). DFT calculations show that the Ccarbene-Si bond in 3 is formed by the donation of the lone pair of electrons on the Ccarbene atom to the SiI2 moiety, while the pi-back-bonding of the lone pair of electrons on the Si atom to the Ccarbene atom is negligible. The presence of the lone pair of electrons on the silicon atom in 3 is also evidenced by its reaction with N3SiMe3 to form the cAAC-silaimine complex [(cAACMe)Si(NSiMe3)I2] (4). Compound 3 reacted with IiPrMe (:C{N(iPr)CMe}2) in n-hexane to form the NHC-cAAC-silyliumylidene iodide [cAACMe(SiI)IiPrMe]I (5), which was then reacted with two equivalents of KC8 in toluene to furnish [cAACMeSi(IiPrMe)] (6). The experimental and theoretical studies suggest that 6 can be described as a bent silaallene with a perturbed electronic structure, which can be attributed to the different donor acceptor properties of cAACMe and IiPrMe. Compounds 3-6 were elucidated by NMR spectroscopy, X-ray crystallography, and theoretical studies. PMID- 27560616 TI - Prediction of Protein Structure Using Surface Accessibility Data. AB - An approach to the de novo structure prediction of proteins is described that relies on surface accessibility data from NMR paramagnetic relaxation enhancements by a soluble paramagnetic compound (sPRE). This method exploits the distance-to-surface information encoded in the sPRE data in the chemical shift based CS-Rosetta de novo structure prediction framework to generate reliable structural models. For several proteins, it is demonstrated that surface accessibility data is an excellent measure of the correct protein fold in the early stages of the computational folding algorithm and significantly improves accuracy and convergence of the standard Rosetta structure prediction approach. PMID- 27560617 TI - Multicomponent One-Pot Synthesis of 3-Tetrazolyl and 3-Imidazo[1,2-a]pyridin Tetrazolo[1,5-a]quinolines. AB - A series of 18 3-tetrazolyl-tetrazolo[1,5-a]quinolines were synthesized in 21-90% yields via a novel one-pot Ugi-azide/SNAr/ring-chain azido-tautomerization process. We report also the synthesis of 10 3-imidazo[1,2-a]pyridin-tetrazolo[1,5 a]quinolines in 28-94% yields via a novel one-pot Groebke-Blackburn Bienayme/SNAr/ring-chain azido-tautomerization process. Both synthetic strategies involve the use of microwaves or ultrasound, and catalyst-free conditions. Finally, we show the synthesis of the tetrazolo[1,5-a]quinoline-3-carbaldehyde and tetrazolo[1,5-a]quinoline-3-dimethyl acetal at room temperature in methanol as solvent. PMID- 27560618 TI - Synthesis and Characterization of [XeOXe](2+) in the Adduct-Cation Salt, [CH3 CN- - -XeOXe- - -NCCH3 ][AsF6 ]2. AB - Acetonitrile and [FXeOXe- - -FXeF][AsF6 ] react at -60 degrees C in anhydrous HF (aHF) to form the CH3 CN adduct of the previously unknown [XeOXe](2+) cation. The low-temperature X-ray structure of [CH3 CN- - -XeOXe- - -NCCH3 ][AsF6 ]2 exhibits a well-isolated adduct-cation that has among the shortest Xe-N distances obtained for an sp-hybridized nitrogen base adducted to xenon. The Raman spectrum was fully assigned by comparison with the calculated vibrational frequencies and with the aid of (18) O-enrichment studies. Natural bond orbital (NBO), atoms in molecules (AIM), electron localization function (ELF), and molecular electrostatic potential surface (MEPS) analyses show that the Xe-O bonds are semi ionic whereas the Xe-N bonds may be described as strong electrostatic (sigma hole) interactions. PMID- 27560619 TI - Prevention and Control of Seasonal Influenza with Vaccines. AB - This report updates the 2015-16 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 influenza season. MMWR Morb Mortal Wkly Rep 2015;64:818-25). Routine annual influenza vaccination is recommended for all persons aged >=6 months who do not have contraindications. For the 2016-17 influenza season, inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in a trivalent formulation (RIV3). In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013-14 and 2015-16 seasons, for the 2016-17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used. Vaccine virus strains included in the 2016-17 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1)-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (Victoria lineage). Quadrivalent vaccines will include an additional influenza B virus strain, a B/Phuket/3073/2013-like virus (Yamagata lineage).Recommendations for use of different vaccine types and specific populations are discussed. A licensed, age-appropriate vaccine should be used. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. Information in this report reflects discussions during public meetings of ACIP held on October 21, 2015; February 24, 2016; and June 22, 2016. These recommendations apply to all licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (http://www.cdc.gov/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information. PMID- 27560621 TI - Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery. AB - INTRODUCTION: Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre clinically in recent years. Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E based polymeric micelles with emphasis on the use of alpha-tocopherol, D-alpha tocopheryl succinate (alpha-TOS) and its conjugates such as D-alpha-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed. PMID- 27560620 TI - Micropapillary colorectal carcinoma: clinical, pathological and molecular properties, including evidence of epithelial-mesenchymal transition. AB - AIMS: Colorectal carcinoma (CRC) with micropapillary (MP) features has only been described recently and is still being characterized. METHODS AND RESULTS: We reviewed the clinicopathological and molecular features of 42 CRC with MP features. Twenty-nine cases were also evaluated for immunohistochemical evidence of epithelial-mesenchymal transition (EMT). The extent of MP features within our cohort ranged from 5% (13 cases) to 100% (one case). Twenty-seven cases featured prominent cribriforming with dirty necrosis in the non-MP component; nine displayed mucinous features. Twenty-four of 29 cases (83%) demonstrated evidence of EMT. Thirty-six cases (86%) showed advanced T-category (pT3 or pT4), 31 (74%) had lymph node metastases and 23 (55%) had distant metastases. Median overall follow-up was 36 months. Seventeen patients (40%) died of disease, with median survival of 23 months. Mutations were seen in 17 of 31 tested cases (55%), including 11 KRAS mutations and four BRAF V600E mutations. Microsatellite instability testing was performed on 21 cases; all were microsatellite-stable. Compared to a cohort of 972 conventional CRC, MP CRC was more likely to present as stage IV disease (P < 0.001), but patients with MP CRC showed no significant differences in overall survival after adjusting for stage. CONCLUSIONS: Micropapillary features in CRC portend a high likelihood of advanced local disease and distant metastases. MP CRC is often associated with a cribriform pattern elsewhere in the tumour and cystic nodal metastases with prominent necrosis. They also show frequent mutations in KRAS and BRAF. Immunohistochemical evidence of EMT is common in MP CRC. PMID- 27560622 TI - Contribution of CD8+ T cells to inflammatory cytokine production in systemic sclerosis (SSc). AB - Only limited attention has been paid to the role of CD8 + T cells in the etiopathogenesis and progression of systemic sclerosis (SSc). CD8 + T cells may have autoantigen-specific and pro-inflammatory but also immunomodulatory properties. To investigate the differentiation of CD8 + T cells, staining of cell surface factors and of chemokine receptors were performed. In addition, the cytokine-producing ability of circulating CD8 + T cells and their sensitivity to suppression by regulatory T cells (Tregs) were compared between patients with diffuse (dcSSc) or limited cutaneous SSc (lcSSc) and healthy individuals. We identified CD8 + T cells as producers of pro-inflammatory type-2 cytokines with a significant contribution of memory CD8 + T cells. Memory CD8 + T cells of SSc patients stayed unaltered after suppression with autologous Tregs. Expression of chemokine receptors was significantly correlated with intracellular cytokine production in CD8 + T cells with a clear dichotomy of type 1 and type 2 cytokines. High levels of intracellular cytokines, such as interleukin-(IL)-4, IL 13 and tumor-necrosis-factor-alpha (TNFalpha) were positively associated with the presence of Scl-70 or anti-centromere antibodies and negatively with the administration of glucocorticoids. Administration of glucocorticoids was positively associated with higher IFNgamma production. Lack of anti-centromere antibodies and therapy with methotrexate were positively associated with higher intracellular IL-10 production. CD8 + T cells may significantly contribute to inflammation in SSc. Our findings suggest to not only focus on T helper cells in the development of therapeutic strategies but also to consider the role of CD8 + T cells in the etiopathogenesis and perpetuation of SSc. PMID- 27560623 TI - Patients "At Risk" of Suffering from Persistent Complaints after Mild Traumatic Brain Injury: The Role of Coping, Mood Disorders, and Post-Traumatic Stress. AB - Although most patients recover fully following mild traumatic brain injury (mTBI), a minority (15-25%) of all patients develop persistent post-traumatic complaints (PTC) that interfere with the resumption of previous activities. An early identification of patients who are at risk for PTC is currently performed by measuring the number of complaints in the acute phase. However, only part of this group will actually develop persisting complaints, stressing the need for studies on additional risk factors. This study aimed to compare this group of patients with many complaints with patients with few and no complaints to identify potential additional discriminating characteristics and to evaluate which of these factors have the most predictive value for being at risk. We evaluated coping style, presence of psychiatric history, injury characteristics, mood-related symptoms, and post-traumatic stress. We included 820 patients (Glasgow Coma Scale [GCS] score 13-15) admitted to three level-1 trauma centers as part of the UPFRONT-study. At 2 weeks after injury, 60% reported three or more complaints (PTC-high), 25% reported few complaints (PTC-low), and 15% reported no complaints (PTC-zero). Results showed that PTC-high consisted of more females (78% vs. 73% and 52%, p < 0.001), were more likely to have a psychiatric history (7% vs. 2% and 5%), and had a higher number of reported depression (22% vs. 6% and 3%, p < 0.001), anxiety (25% vs. 7% and 5%), and post-traumatic stress (37% vs. 27% and 19%, p < 0.001) than the PTC-low and PTC-zero groups. We conclude that in addition to reported complaints, psychological factors such as coping style, depression, anxiety, and post-traumatic stress symptoms had the highest predictive value and should be taken into account in the identification of at risk patients for future treatment studies. PMID- 27560624 TI - Incidence and Predictive Factors of Postprandial Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass: A Five year Longitudinal Study. AB - BACKGROUND: Postprandial hyperinsulinemic hypoglycemia (PHH) is often reported after Roux-en-Y gastric bypass (RYGB). In the absence of a prospective study, the clinical and biological determinants of PHH remain unclear. OBJECTIVE: To determine the incidence and predictive factors of PHH after RYGB. METHODS: Participants were 957 RYGB patients enrolled in an ongoing longitudinal cohort study. We analyzed the results of an oral glucose tolerance test (OGTT) routinely performed before surgery and 1 and/or 5 years after. PHH was defined as blood glucose < 50 mg/dL AND plasma insulin > 3 mU/L at 120 minutes post glucose challenge. Validated indices of insulin sensitivity (Matsuda index), beta-cell function (Insulinogenic index), and beta-cell mass (fasting C-peptide: glucose ratio) were calculated, from glucose, insulin, and c-peptide values measured during OGTT. RESULTS: OGTT results were available in all patients at baseline, in 85.6% at 12 months and 52.8% at 60 months. The incidence of PHH was 0.5% at baseline, 9.1% * and 7.9%* at 12 months and 60 months following RYGB (*: P < 0.001). In multivariate logistic regression analysis, PHH after RYGB was independently associated with lower age (P = 0.005), greater weight loss (P = 0.031), as well as higher beta-cell function (P = 0.002) and insulin sensitivity (P < 0.001), but not with beta-cell mass (P = 0.381). A preoperative elevated beta-cell function was an independent predictor of PHH after RYGB (receiver operating characteristics curve area under the curve 0.68, P = 0.04). CONCLUSIONS:: The incidence of PHH significantly increased after RYGB but remained stable between 1 and 5 years. The estimation of beta-cell function with an OGTT before surgery can identify patients at risk for developing PHH after RYGB. PMID- 27560625 TI - Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice. AB - BACKGROUND: Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns). METHODS: We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor beta1 (TGF-beta1), PRR, FcRn and renal metabolism of IgG in a mice model of anti glomerular basement membrane glomerulonephritis (anti-GBM GN). RESULTS: IgG deposition and expressions of FcRn and PRR were enhanced at glomeruli and urinary IgG levels increased in anti-GBM GN. Aliskiren attenuated anti-GBM GN with reduction of proteinuria and cortical expressions of fibronectin and TGF-beta1. In addition, aliskiren suppressed the renal cortical expressions of FcRn and PRR. Aliskiren also reduced the glomerular IgG depositions and the urinary IgG levels albeit with increased circulating serum IgG levels. CONCLUSION: These results suggest that suppression of FcRn and PRR and regulation of IgG metabolism may be related to the attenuation of anti-GBM GN by aliskiren. PMID- 27560626 TI - Associations of Lifestyle, Medication, and Socio-Demographic Factors with Disability in People with Multiple Sclerosis: An International Cross-Sectional Study. AB - OBJECTIVE: Emerging evidence links modifiable lifestyle risk factors to disease progression in multiple sclerosis (MS). We sought further evidence around this hypothesis through detailed analysis of the association with disability of lifestyle behaviours of a large international sample of people with MS. MATERIALS AND METHODS: A total of 2469 people with MS from 57 countries provided self reported data via cross-sectional online survey on lifestyle (mostly with validated tools) and the primary outcome measure, disability (Patient Determined Disease Steps), categorised from 8 steps into 3 categories, mild, moderate and major disability. Multinomial logistic regression modelling derived relative risk ratios (RRRs) for disability categories. RESULTS: RRRs of having moderate vs mild disability were: diet (per 30 points on 100 point scale) 0.72 (95%CI 0.52-0.98), ever smoking 1.32 (1.06-1.65), exercise (moderate/high vs low) 0.35 (0.28-0.44), latitude (per degree from the equator) 1.02 (1.01-1.04), and number of comorbidities (2 vs none) 1.43 (1.04-1.95), (3 vs none) 1.56 (1.13-2.16). RRRs of having major vs mild disability were: exercise (moderate/high vs low) 0.07 (0.04 0.11), alcohol consumption (moderate vs low) 0.45 (0.30-0.68), plant-based omega 3 supplementation 0.39 (0.18-0.86), and disease-modifying medication use 0.45 (0.29-0.70). CONCLUSIONS: Healthier lifestyle has strong associations with disability in our large international sample of people with MS, supporting further investigation into the role of lifestyle risk factors in MS disease progression. PMID- 27560628 TI - Interactions between uranium(vi) and phosphopeptide: experimental and theoretical investigations. AB - Uranium is an essential actinide element in nuclear fuel cycles, and protein phosphorylation is one type of most important post-translational modifications. It is of great interest to study the interactions between uranyl ions and phosphorylated proteins. In this study, a phosphorylated pentapeptide (WpTPpTW, P(1)) motif was designed as a model to mimic possible coordination sites in genuine phosphorylated proteins. Electrospray ionization mass spectrometry (ESI MS) results suggested that uranyl-P(1) complexes with chemical stoichiometry of 1 : 1 and 1 : 2 were both available. The conditional stability constant of the 1 : 1 complex uranyl-P(1) was determined to be 6.6 +/- 0.2 at pH 4.0 by tryptophan fluorescence titrations, which is almost three orders of magnitude higher than that of the complex of nonphosphorylated peptide. The results of extended X-ray absorption fine structure (EXAFS) combined with density functional theoretical calculations suggested that uranyl ions coordinated with one phosphoryl and carboxyl groups of P(1) in a mono-dentate fashion, and three water molecules. This study on the simple metal-peptide system could provide basic information for locating the uranyl coordination site in some important phosphorylated proteins which is useful for evaluating the chemical toxicity of uranyl in vivo. PMID- 27560629 TI - Fish Neurogenesis in Context: Assessing Environmental Influences on Brain Plasticity within a Highly Labile Physiology and Morphology. AB - Fish have unusually high rates of brain cell proliferation and neurogenesis during adulthood, and the rates of these processes are greatly influenced by the environment. This high level of cell proliferation and its responsiveness to environmental change indicate that such plasticity might be a particularly important mechanism underlying behavioral plasticity in fish. However, as part of their highly labile physiology and morphology, fish also respond to the environment through processes that affect cell proliferation but that are not specific to behavioral change. For example, the environment has nonspecific influences on cell proliferation all over the body via its effect on body temperature and growth rate. In addition, some fish species also have an unusual capacity for sex change and somatic regeneration, and both of these processes likely involve widespread changes in cell proliferation. Thus, in evaluating the possible behavioral role of adult brain cell proliferation, it is important to distinguish regionally specific responses in behaviorally relevant brain nuclei from global proliferative changes across the whole brain or body. In this review, I first highlight how fish differ from other vertebrates, particularly birds and mammals, in ways that have a bearing on the interpretation of brain plasticity. I then summarize the known effects of the physical and social environment, sex change, and predators on brain cell proliferation and neurogenesis, with a particular emphasis on whether the effects are regionally specific. Finally, I review evidence that environmentally induced changes in brain cell proliferation and neurogenesis in fish are mediated by hormones and play a role in behavioral responses to the environment. PMID- 27560627 TI - Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production. AB - Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-lambda1, 2 and 3, and IFN-beta through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen 1, and significantly increased the levels of MuV-induced IFN-lambda1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-lambda1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection. PMID- 27560630 TI - Current status of iodine deficiency-related disorders prophylaxis in Slovakia - the life's work of Julian Podoba remained unfinished. AB - OBJECTIVE: Prophylaxis of iodine deficiency-related disorders with iodized salt in Slovakia was introduced in 1951. This prophylactic measure yielded remarkably good results. Endemic goiter and endemic cretinism disappeared. Sufficient iodine intake, mainly in children and adolescents, was confirmed in several local and international studies carried out in the period 1991-95. Unfortunately, since seventies, there has been no institution which would have dealt with iodine prophylaxis in such an extent as this important measure of Slovak preventive medicine would require. Neither systematic monitoring of iodine intake nor systematic population epidemiological studies have been carried out. We do not have any data on the iodine intake in pregnant women, the most vulnerable population group in relation to the iodine deficiency. During the period June 2014 - October 2015, we examined iodine excretion in 426 probands from three regions of Slovakia with an emphasis on the pregnant women. RESULTS: Iodine intake was found to be sufficient, even more than adequate, in all age groups of Slovak population. The only population group with iodine intake borderline or very mild iodine deficiency are pregnant women. CONCLUSIONS: 1/ Iodine nutrition in Slovakia is generally sufficient, even oversteps the requirement, with the exception of pregnant women. Iodine intake in pregnant women should be fortified by iodine containing multivitamin preparations. 2/ We recommend to include the examination of urinary iodine into the screening of thyropathies in early pregnancy. 3/ It is not enough to implement the iodine deficiency-related disorders prevention programs, it is also necessary to stabilize such programs over time and balance the benefits with possible side effects of this program. PMID- 27560631 TI - Handedness and gender influence blood pressure in young healthy men and women: A pilot study. AB - OBJECTIVE: The type and level of sex steroids influence blood pressure (BP). It has been suggested that functional brain asymmetries may be influenced by sex hormones. In addition, there are inter-arm differences in BP not yet related with handedness. In this study, we hypothesize a possible association between sex hormones, handedness, and inter-arm differences in blood pressure. METHODS: To analyze this hypothesis, we measured BP in the left and right arm of the left and right handed adult young men and women in menstrual and ovulatory phase and calculated their mean arterial pressure (MAP). RESULTS: Significant differences depending on sex, arm, handedness or phase of the cycle were observed. MAP was mostly higher in men than in women. Remarkably, in women, the highest levels were observed in the left handed in menstrual phase. Interestingly, the level of handedness correlated negatively with MAP measured in the left arm of right handed women in the ovulatory phase but positively with the MAP measured in the right arm of right-handed women in the menstrual phase. CONCLUSIONS: These results may reflect an asymmetrical modulatory influence of sex hormones in BP control. PMID- 27560632 TI - The prepulse inhibition deficit appearance is largely independent on the circadian cycle, body weight, and the gender of vasopressin deficient Brattleboro rat. AB - OBJECTIVE: A disturbance of sensorimotor gating measured by prepulse inhibition of acoustic startle (PPI) is one of the best tests of the schizophrenia-like behavior. Vasopressin was implicated in the development of schizophrenia; therefore, the naturally occurring vasopressin-deficient Brattleboro rat has been suggested to be a reliable non-pharmacological animal model. However, previous studies focusing on PPI deficit did not use proper control and despite clear gender differences in the development of the disorder, the effect of gender has been mostly neglected. METHODS: First, we compared the "noise" and "tone" type prepulse at 73-77-81 dB intensity during the light or dark phase using small (~150 g) or big (~500 g) Wistar rats. The test parameters were validated by a pharmacological schizophrenia model (30 mg/kg ketamine i.p.). Than male, female, and lactating vasopressin-deficient animals were compared with +/+ ones. RESULTS: We established that the prepulse "noise" type is not optimal for PPI testing. The cycle of the day as well as the body weight had no effect on PPI. Even if we compared vasopressin-deficient animals with their closely related +/+ controls, the PPI deficiency was visible with more pronounced effect at 77 dB prepulse intensity similarly to pharmacological schizophrenia model. Despite our expectation, the gender as well as lactation had no effect on the vasopressin deficiency induced PPI deficit. CONCLUSIONS: The present data confirmed and extended our previous studies that vasopressin-deficient rat is a good model of schizophrenia. It seems that female as well as lactating Brattleboro rats are useful tools for testing putative novel antipsychotics in line with special attention required for schizophrenic women. PMID- 27560633 TI - Newly diagnosed primary hypothyroidism applicant with massive pericardial effusion and acute renal failure. AB - OBJECTIVE: While non-symptomatic pericardial effusion is seen in primary hypothyroidism, massive pericardial effusion is a very rare finding. In the literature, newly diagnosed primary hypothyroidism cases presenting with massive pericardial effusion or acute renal failure are present, but we did not encounter any case first presenting with combination of two signs. In this case report, primary hypothyroidism case that presenting with massive pericardial effusion and acute renal failure will be discussed. Subject and Results. Forty-eight years old male patient was hospitalized with shortness of breath, chest pain, swelling of the eyelids and bilateral limbs complaints. On chest radiograph heart shadow was deleted, pleural effusion was present until the middle zone of the left lung. Biochemical parameters (urea, creatinine, alanine aminotransferase aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatine kinase, Troponin I, CK-MB, erythrocyte sedimentation rate, c-reactive protein) and thyroid stimulating hormone (TSH, 52.6 MUg/ml), free triiodothyronine (T3, 0.61pg/ml), free thyroxine (T4, 0.12 ng/dl), anti thyroperoxydase (343 IU/ml), anti thyroglobulin (1604 IU/ml), were analyzed. The patient underwent pericardiocentesis. Levothyroxine treatment started with a dose of 0.05 mg per day and increased gradually until the optimum dose provided. At the end of the third month, the values of TSH, free T4, and free T3 were measured (2.3 MUg/ml, 1.1 ng/dl, 2.54 pg/ml, respectively). The patient recovered completely and pericardial effusion was not detected in echocardiography. CONCLUSION: Massive PE and acute renal failure due to primary hypothyroidism is a rare clinical condition. Primary hypothyroidism should be kept in mind in patients with symptoms like shortness of breath, chest pain, and generalized edema; moreover, when acute renal failure and PE were detected. It should be considered that patient's biochemical parameters can improve starting from the two weeks after levothyroxine treatment started with pericardiocentesis in severe symptomatic patients. PMID- 27560634 TI - Pancrelipase treatment in a patient with the history of Roux-en-Y gastric bypass operation that developed resistant hypocalcemia secondary to total thyroidectomy. AB - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an independent risk factor for moderate hypocalcaemia and may lead to the development of resistant hypocalcaemia following thyroid surgery. Subject and Results. A 35-year old female patient was referred to our hospital by her family physician for treatment of resistant hypocalcaemia. The patient underwent RYGB three years ago and a total thyroidectomy for a benign thyroid nodule one year ago. Calcitriol, calcium carbonate, magnesium oxide, and ergocalciferol therapeutic dosages were incremented. Despite dosage increments, the desired calcium levels were not achieved. In the sixth month after admission to our hospital, pancrelipase was added to patient's treatment scheme. On the following visit, a good calcium increase had been achieved. CONCLUSION: This report presents a case history of RYGB and resistant hypocalcaemia, which developed after thyroid surgery and positively responded to pancrelipase treatment. PMID- 27560635 TI - Comparison of clinical and biochemical variables in type 2 diabetes mellitus patients and their first-degree relatives with metabolic syndrome in Benin City, Nigeria: A cross sectional case controlled study. AB - OBJECTIVE: Type 2 diabetes mellitus (T2DM) is characterized by a relative insulin deficiency or insulin resistance. It is also associated with a cluster of metabolic abnormalities, including hyper-tension and dyslipidemia. Although there are many studies that have studied the metabolic abnormalities in T2DM patients with metabolic syndrome (MetS), only few of them have assessed the metabolic abnormalities in their first-degree relatives (FDRs) who had MetS. The aim of this study is to compare the clinical and biochemical variables in T2DM subjects and their FDRs without diabetes in Benin City, Nigeria. METHODS: This is a cross sectional case control study including 124 T2DM patients, 96 FDR of T2DM subjects, and 96 controls recruited using convenience sampling. Data were collected using a questionnaire-administered technique. Variables of interest that were assessed included anthropometric indices like waist circumference (WC), hip circumference (HC), waist:hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum lipid profile, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), proteinuria, and microalbuminuria. The 1999 World Health Organization (WHO) criteria were used to make a diagnosis of metabolic syndrome. The Chi-square test was used for comparison of proportions. P-value of less than 0.05 was taken as statistically significant. The student t-test was used to compare means and test for significant differences in the anthropometric and the metabolic indices. RESULTS: The prevalence of the MetS in T2DM persons was 87.1%, 16.7% in the FDR group, and 13.5% in the control group according to the WHO criteria. The mean value of HbA1c was significantly higher in T2DM subjects with MetS (p<0.05). The mean values of WC, FPG, total cholesterol, HDL cholesterol, and LDL cholesterol were higher in subjects with MetS in the T2DM group than in persons with MetS in the FDR group though not significant (p>0.05). The mean values of WHR, BMI, SBP, DBP, and triglyceride were higher in persons with the MetS in the FDR group than in persons with the MetS in the T2DM group. The difference in the BMI and SBP was significant (p<0.05). CONCLUSION: The prevalence of MetS in subjects with T2DM in Nigeria is very high. Though, all the biochemical and clinical indices were higher in T2DM subjects with MetS, the mean HbA1c, BMI, and SBP was significantly higher when compared to their FDR who also have MetS. PMID- 27560636 TI - Effect of hypoxia on the expression of genes encoding insulin-like growth factors and some related proteins in U87 glioma cells without IRE1 function. AB - OBJECTIVE: The aim of the present study was to investigate the effect of hypoxia on the expression of genes encoding insulin-like growth factors (IGF1 and IGF2), their receptor (IGF1R), binding protein-4 (IGFBP4), and stanniocalcin 2 (STC2) in U87 glioma cells in relation to inhibition of endoplasmic reticulum stress signaling mediated by IRE1 (inositol requiring enzyme 1) for evaluation of their possible significance in the control of tumor growth. METHODS: The expression of IGF1, IGF2, IGF1R, IGFBP4, and STC2 genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia was studied by qPCR. RESULTS: The expression of IGF1 and IGF2 genes is down-regulated in glioma cells without IRE1 signaling enzyme function in comparison with the control cells. At the same time, the expression of IGF1R, IGFBP4, and STC2 genes was up-regulated in glioma cells upon inhibition of IRE1, with more significant changes for IGFBP4 and STC2 genes. We also showed that hypoxia does not change significantly the expression of IGF1, IGF2, and IGF1R genes but up-regulated IGFBP4 and STC2 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in glioma cells does not change significantly the effect of hypoxia on the expression of IGF1, IGF1R, and IGFBP4 genes but introduces sensitivity of IGF2 gene to hypoxic condition. Thus, the expression of IGF2 gene is resistant to hypoxia only in control glioma cells and significantly down-regulated in cells without functional activity of IRE1 signaling enzyme, which is central mediator of the unfolded protein response and an important component of the tumor growth as well as metabolic diseases. CONCLUSIONS: Results of this study demonstrate that the expression of IGF1 and IGF1R genes is resistant to hypoxic condition both in control U87 glioma cells and cells without IRE1 signaling enzyme function. However, hypoxia significantly up-regulates the expression of IGFBP4 gene independently on the inhibition of IRE1 enzyme. These data show that proteins encoded by these genes are resistant to hypoxia except IGFBP4 and participate in the regulation of metabolic and proliferative processes through IRE1 signaling. PMID- 27560637 TI - Role of interlekin-35 as a biomarker in patients with newly diagnosed Hashimoto's thyroiditis. AB - OBJECTIVE: Interleukin-35 (IL-35), an interleukin-12 (IL-12) cytokine family member, is shown to be a potent immunosuppressive and anti-inflammatory cytokine. Inducible regulatory T cells (Tregs) produce IL-35 that mediates the immune inhibitory function of Tregs. Growing evidence revealed that upregulation of IL 35 expression may play a critical role in the prevention of autoimmune diseases in various experimental autoimmunity models and vice versa. Hashimoto's thyroiditis (HT) is considered to be a Treg cell-related autoimmune disease with loss of self-tolerance. METHODS: One hundred-twenty eight subjects, newly diagnosed hypothyroid HT patients [56 overt (Group 1), 72 subclinical hypothyroid (Group 2)] and 38 healthy controls (Group 3) were enrolled in the study. The levels of serum IL-35 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum IL-35 levels were lower in the HT group when compared with subclinical HT group [304.5 (834.6) pg/ml vs. 636.1 (1542.0) pg/ml, p=0.004] and control cases [304.5 (834.6) pg/ml vs. 1064.7 (2526.8) pg/ml, p<0.001]. Serum IL-35 levels were inversely associated with thyroid stimulating hormone (TSH; rs= 0.396, p<0.001) and anti-thyroid peroxidase antibodies (TPOAb; rs=-0.571, p<0.001) in whole group. Serum IL-35 were negatively associated with TSH (rs= 0.264, p=0.003) and TPOAb (rs=-0.735, p<0.001) in patients with Hashimoto's thyroiditis (Group 1 + Group 2). CONCLUSION: The results suggest that IL-35 may play a role in the pathogenesis of HT. PMID- 27560638 TI - Gestational diabetes: An overview with attention for developing countries. AB - Gestational diabetes mellitus (GDM) is defined as a glucose intolerance that occurs for the first time or it is first identified during pregnancy. The GDM etiology is multifactorial. It has not completely been established yet and several known risk factors may contribute to its onset. To date, there are no shared guidelines on the management and follow-up, especially regarding the low income countries. In this paper, we describe the state of art about epidemiology, physiopathology, diagnosis, and management of GDM. Moreover, we focus on the current state in low income countries trying to outline basis for further research. PMID- 27560639 TI - Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview. AB - The present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the differences in the local responses elicited by neuropeptides, there exist certain functional similarities in the effects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42), implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation. PMID- 27560640 TI - Progress in micro RNA focused research in endocrinology. AB - Micro RNAs (miRNAs) are small regulatory molecules of increasing biologists' interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs. miRNA biogenesis is realized by key enzymes, Drosha and Dicer. miRNA/mRNA interaction depends on binding to RNA-induced silencing complex. Today, complete commercially available methodical proposals for miRNA investigation are available. There are techniques allowing the identification of new miRNAs and new miRNA targets, validation of predicted targets, measurement of miRNAs and their precursor levels, and validation of physiological role of miRNAs under in vitro and in vivo conditions. miRNAs have been shown to influence gene expression in several endocrine glands, including pancreas, ovary, testes, hypothalamus, and pituitary. PMID- 27560641 TI - Micro RNAs: an arguable appraisal in medicine. AB - Micro RNAs (miRNAs) represent a newly discovered class of regulatory molecules in the human body. miRNA is a short double stranded RNA sequence interfering with mRNA, causing in most cases, inhibition of translation. Synthesis of miRNAs shows an increasing developmental pattern and postnatally miRNAs are synthesized in all cells possessing transcriptional machinery. miRNAs usually target several mRNAs and therefore conclusive evidences proving their functions are not always ease to be acquired. In spite of this difficulty, functions of miRNAs were firmly established in the development, the cardiovascular and neural diseases, and cancer. Many miRNAs have been reported to be associated with physiological state of cells and/or tissues. This finding becomes fundamental, especially when consider that these miRNAs can be released from cell into intracellular space or circulation. Correlation between miRNA production in tissues and its contribution to multisource miRNA pool in the circulation is in a focus of biomarker-oriented researchers. Recently, circulating miRNAs have been suggested to be applicable as biomarkers in several types of cancer, cardiovascular injury, and diabetes. Role of miRNAs in the organism intercellular signaling is still under the broad investigation. Several miRNA mimics, intended for treatment of disease, are being currently tested in the clinical trials. PMID- 27560642 TI - Free-Radical Triggered Ordered Domino Reaction: An Approach to C-C Bond Formation via Selective Functionalization of alpha-Hydroxyl-(sp(3))C-H in Fluorinated Alcohols. AB - A free-radical mediated highly ordered radical addition/cyclization/(sp(3))C C(sp(3)) formation domino reaction is developed. Three new C-C bonds are formed one by one in a mixed system. Furthermore, it represents the first example of cascade C-C bond formation via selective functionalization of alpha-hydroxyl C(sp(3))-H in fluorinated alcohols. PMID- 27560643 TI - Traction injury of the brachial plexus confused with nerve injury due to interscalene brachial block: A case report. AB - INTRODUCTION: Shoulder surgery is often performed with the patient in the so called "beach-chair position" with elevation of the upper part of the body. The anesthetic procedure can be general anesthesia and/or regional block, usually interscalenic brachial plexus block. We present a case of brachial plexus palsy with a possible mechanism of traction based on the electromyographic and clinical findings, although a possible contribution of nerve block cannot be excluded. PRESENTATION OF THE CASE: We present a case of a 62 year-old female, that suffered from shoulder fracture-dislocation. Open reduction and internal fixation were performed in the so-called "beach-chair" position, under combined general regional anesthesia. In the postoperative period complete motor brachial plexus palsy appeared, with neuropathic pain. Conservative treatment included analgesic drugs, neuromodulators, B-vitamin complex and physiotherapy. Spontaneous recovery appeared at 11 months. DISCUSION: in shoulder surgery, there may be complications related to both anesthetic technique and patient positioning/surgical maneuvers. Regional block often acts as a confusing factor when neurologic damage appears after surgery. Intraoperative maneuvers may cause eventual traction of the brachial plexus, and may be favored by the fixed position of the head using the accessory of the operating table in the beach-chair position. CONCLUSION: When postoperative brachial plexus palsy appears, nerve block is a confusing factor that tends to be attributed as the cause of palsy by the orthopedic surgeon. The beach chair position may predispose brachial plexus traction injury. The head and neck position should be regularly checked during long procedures, as intraoperative maneuvers may cause eventual traction of the brachial plexus. PMID- 27560644 TI - Electron spin dynamics and spin-lattice relaxation of trityl radicals in frozen solutions. AB - Electron spin-lattice relaxation of two trityl radicals, d24-OX063 and Finland trityl, were studied under conditions relevant to their use in dissolution dynamic nuclear polarization (DNP). The dependence of relaxation kinetics on temperature up to 100 K and on concentration up to 60 mM was obtained at X- and W bands (0.35 and 3.5 Tesla, respectively). The relaxation is quite similar at both bands and for both trityl radicals. At concentrations typical for DNP, relaxation is mediated by excitation transfer and spin-diffusion to fast-relaxing centers identified as triads of trityl radicals that spontaneously form in the frozen samples. These centers relax by an Orbach-Aminov mechanism and determine the relaxation, saturation and electron spin dynamics during DNP. PMID- 27560645 TI - An innovative approach combining Animal Performances, nutritional value and sensory quality of meat. AB - This work sets out a methodological approach to assess how to simultaneously control together Animal Performances, nutritional value, sensory quality of meat. Seventy-one young bulls were characterized by 97 variables. Variables of each element were arranged into either 5 homogeneous Intermediate Scores (IS) or 2 Global Indices (GI) via a clustering of variables and analysed together by Principal Component Analysis (PCA). These 3 pools of 5 IS (or 2 GI) were analysed together by PCA to established the links existing among the triptych. Classification on IS showed no opposition between Animal Performances and nutritional value of meat, as it seemed possible to identify animals with a high butcher value and intramuscular fat relatively rich in polyunsaturated fatty acids. Concerning GI, the classification indicated that Animal Performances were negatively correlated with sensory quality. This method appeared to be a useful contribution to the management of animal breeding for an optimal trade-off between the three elements of the triptych. PMID- 27560646 TI - Corrigendum: In vivo assembly of DNA-fragments in the moss, Physcomitrella patens. PMID- 27560647 TI - Dietary Intake and Cardiovascular Risk Factors in Icelanders Following Voluntarily a Low Carbohydrate Diet. AB - BACKGROUND/AIM: Most studies regarding low-carbohydrate diets (LCDs) have been intervention studies. The aim of the current study was to investigate dietary intake and cardiovascular risk factors among individuals who voluntarily follow a LCD. METHODS: A cross-sectional study was conducted (N = 54, 20-66yrs) in Reykjavik, Iceland. Participants recorded food intake for three days. Blood samples were analyzed for cardiovascular risk factors. RESULTS: Nearly half of the participants were obese and around 60% had been on a LCD for >= 6 months. Fifty percent claimed they had lost weight during the past month. The median intake of carbohydrate, protein and fat were 8%, 22% and 68% E (hereof 25% saturated fatty acids), respectively. The consumption of bread and wholegrain cereals was very low (<5g/day), including the intake of dietary fiber (11g/day). Median fruit intake was 12 g/day. Intake of red meat and meat products was double that of the general population or ~900 g/week. Median intake of vitamins and minerals were mostly higher than the estimated average requirements. Cardiovascular risk factors were mostly within normal range. Mean blood lipids were slightly elevated although the high density lipoprotein/total cholesterol ratio was normal. CONCLUSION: Despite poor diet quality and high prevalence of obesity, individuals who voluntarily follow a LCD have cardiovascular risk factors mostly within reference range. These individuals consume very low amounts of carbohydrates and high amounts of fat and saturated fat acids. Intake of red meat and processed meat exceeds recommended intake. Very low intake of whole grain cereals and fruits results in low intake of fiber. Long term health implications need to be examined further in longitudinal studies. PMID- 27560649 TI - Molecular evidence of two cryptic species of Stramonita (Mollusca, Muricidae) in the southeastern Atlantic coast of Brazil. AB - Snails of the genus Stramonita are commonly found in the rocky intertidal habitat of the western Atlantic Ocean coast. They belong to a monophyletic taxon that occurs along the tropical and warm-temperate Atlantic and eastern Pacific rocky shores. This genus comprises different valid species and members of the S. haemastoma complex. In the present study, samples of Stramonita were collected from three different regions of southeastern Brazil. Partial sequences of two mitochondrial genes, COI and 16S rRNA, were used to compare nucleotides sequences between Stramonita specimens. Levels of nucleotide divergence greater than 2% across the three sampled regions were used for differentiation at the species level. One of the identified species was S. brasiliensis, which has recently been described by molecular analysis; the other species may represent S. haemastoma, not yet described in the southeastern Brazilian coast. PMID- 27560648 TI - Comparative genomics of an endophytic Pseudomonas putida isolated from mango orchard. AB - We analyzed the genome sequence of an endophytic bacterial strain Pseudomonas putida TJI51 isolated from mango bark tissues. Next generation DNA sequencing and short read de novo assembly generated the 5,805,096 bp draft genome of P. putida TJI51. Out of 6,036 protein coding genes in P. putida TJI51 sequences, 4,367 (72%) were annotated with functional specifications, while the remaining encoded hypothetical proteins. Comparative genome sequence analysis revealed that the P. putida TJI51genome contains several regions, not identified in so far sequenced P. putida genomes. Some of these regions were predicted to encode enzymes, including acetylornithine deacetylase, betaine aldehyde dehydrogenase, aldehyde dehydrogenase, benzoylformate decarboxylase, hydroxyacylglutathione hydrolase, and uroporphyrinogen decarboxylase. The genome of P. putida TJI51 contained three nonribosomal peptide synthetase gene clusters. Genome sequence analysis of P. putidaTJI51 identified this bacterium as an endophytic resident. The endophytic fitness might be linked with alginate, which facilitates bacterial colonization in plant tissues. Genome sequence analysis shed light on the presence of a diverse spectrum of metabolic activities and adaptation of this isolate to various niches. PMID- 27560650 TI - Genome-wide association study of drought-related resistance traits in Aegilops tauschii. AB - The D-genome progenitor of wheat (Triticum aestivum), Aegilops tauschii, possesses numerous genes for resistance to abiotic stresses, including drought. Therefore, information on the genetic architecture of A. tauschii can aid the development of drought-resistant wheat varieties. Here, we evaluated 13 traits in 373 A. tauschii accessions grown under normal and polyethylene glycol-simulated drought stress conditions and performed a genome-wide association study using 7,185 single nucleotide polymorphism (SNP) markers. We identified 208 and 28 SNPs associated with all traits using the general linear model and mixed linear model, respectively, while both models detected 25 significant SNPs with genome-wide distribution. Public database searches revealed several candidate/flanking genes related to drought resistance that were grouped into three categories according to the type of encoded protein (enzyme, storage protein, and drought-induced protein). This study provided essential information for SNPs and genes related to drought resistance in A. tauschii and wheat, and represents a foundation for breeding drought-resistant wheat cultivars using marker-assisted selection. PMID- 27560651 TI - The effect of magnesium on mitotic spindle formation in Schizosaccharomyces pombe. AB - Magnesium (Mg2+), an essential ion for cells and biological systems, is involved in a variety of cellular processes, including the formation and breakdown of microtubules. The results of a previous investigation suggested that as cells grow the intracellular Mg2+ concentration falls, thereby stimulating formation of the mitotic spindle. In the present work, we used a Mg2+-deficient Schizosaccharomyces pombe strain GA2, in which two essential membrane Mg2+ transporter genes (homologs of ALR1 and ALR2 in Saccharomyces cerevisae) were deleted, and its parental strain Sp292, to examine the extent to which low Mg2+ concentrations can affect mitotic spindle formation. The two S. pombe strains were transformed with a plasmid carrying a GFP-alpha2-tubulin construct to fluorescently label microtubules. Using the free Mg2+-specific fluorescent probe mag-fura-2, we confirmed that intracellular free Mg2+ levels were lower in GA2 than in the parental strain. Defects in interphase microtubule organization, a lower percentage of mitotic spindle formation and a reduced mitotic index were also observed in the GA2 strain. Although there was interphase microtubule polymerization, the lower level of mitotic spindle formation in the Mg2+ deficient strain suggested a greater requirement for Mg2+ in this phenomenon than previously thought. PMID- 27560652 TI - Evidence of ectopic recombination and a repeat-induced point (RIP) mutation in the genome of Sclerotinia sclerotiorum, the agent responsible for white mold. AB - Two retrotransposons from the superfamilies Copia and Gypsy named as Copia-LTR_SS and Gypsy-LTR_SS, respectively, were identified in the genomic bank of Sclerotinia sclerotiorum. These transposable elements (TEs) contained direct and preserved long terminal repeats (LTR). Domains related to codified regions for gag protein, integrase, reverse transcriptase and RNAse H were identified in Copia-LTR_SS, whereas in Gypsy-LTR_SS only domains for gag, reverse transcriptase and RNAse H were found. The abundance of identified LTR-Solo suggested possible genetic recombination events in the S. sclerotiorum genome. Furthermore, alignment of the sequences for LTR elements from each superfamily suggested the presence of a RIP (repeat-induced point mutation) silencing mechanism that may directly affect the evolution of this species. PMID- 27560653 TI - Adsorption of poly(ethylene succinate) chain onto graphene nanosheets: A molecular simulation. AB - Understanding the interaction between single polymer chain and graphene nanosheets at local and global length scales is essential for it underlies the mesoscopic properties of polymer nanocomposites. A computational attempt was then performed using atomistic molecular dynamics simulation to gain physical insights into behavior of a model aliphatic polyester, poly(ethylene succinate), single chain near graphene nanosheets, where the effects of the polymer chain length, graphene functionalization, and temperature on conformational properties of the polymer were studied comparatively. Graphene functionalization was carried out through extending the parameters set of an all-atom force field. The results showed a significant conformational transition of the polymer chain from three dimensional statistical coil, in initial state, to two-dimensional fold, in final state, during adsorption on graphene. The conformational order, overall shape, end-to-end separation statistics, and mobility of the polymer chain were found to be influenced by the graphene functionalization, temperature, and polymer chain length. Furthermore, the polymer chain dynamics mode during adsorption on graphene was observed to transit from normal diffusive to slow subdiffusive mode. The findings from this computational study could shed light on the physics of the early stages of aliphatic polyester chain organization induced by graphene. PMID- 27560654 TI - Precise reply and clarifications on behalf of Sicilian Public Health Authorities to the case report published by La Rosa and collegues. AB - As a results of the case report "Post-rotavirus vaccine intussusception in identical twins: a case report" recently published on Human Vaccines & Immunotherapy by La Rosa et al., the principal Sicilian Public Health Authorities decided to specify several points and underline some important details omitted by the authors. In particular, aims to underline the remarkable benefit for Sicilian Regional Health service after the introduction of the rotavirus vaccination. Universal mass vaccination against rotavirus is properly managed by the Regional Health Authorities and is contributing to a consistent increase of public health in the Sicilian pediatric population; any modification of such a program should be based on robust scientific evidences. Finally, a single case report should not be considered as a basis to recommend a change in the clinical practice but instead a possible point of start for discussion and research. PMID- 27560655 TI - Comparison of peri-implant clinical and radiographic inflammatory parameters and whole salivary destructive inflammatory cytokine profile among obese and non obese men. AB - The aim of the present cross-sectional retrospective study was to compare the peri-implant clinical and radiographic inflammatory parameters and whole salivary destructive inflammatory cytokine profile among obese and non-obese men. Thirty five obese and 37 non-obese men were included. Information regarding age, obesity, systemic health status, and habits was collected using a questionnaire. Clinical examination to evaluate peri-implant parameters and radiographic examination to assess marginal bone loss were conducted. Levels of interleukin (IL)-6 and IL-1beta in collected un-stimulated whole saliva were measured using enzyme-linked immunosorbent assay. Data was statistically analyzed using Kruskal Wallis test. The mean scores of peri-implant bleeding on probing (P<0.05) and peri-implant probing depth (P<0.05) were significantly higher among obese compared with non-obese individuals. The mean marginal bone loss was also statistically significantly higher among individuals in the test-group compared with the control-group (P<0.05). Whole salivary IL-1beta (P<0.001) and IL-6 (P<0.001) levels were significantly higher among individuals in the test-group compared with the control-group. Clinical and radiographic peri-implant inflammatory parameters were worse, and whole salivary IL-6 and IL-1beta were higher in obese than non-obese subjects. Obese patients are at greater risk of peri-implant inflammation than non-obese healthy subjects. It is highly recommended that clinicians should educate obese patients seeking implant treatment regarding the association between obesity and peri-implant inflammation. In addition, obese patients with osseointegrated implants must follow strict oral hygiene regimen to prevent inflammation and maintain optimum peri-implant tissue health. PMID- 27560656 TI - The effect of ageing on recollection: the role of the binding updating process. AB - The aim of this study was to highlight the underlying process responsible for the age-related deficit in recollection. Through two experiments using the Remember Know-Guess procedure (Gardiner, J. M., & Richardson-Klavehn, A. [2000]. Remembering and knowing. In The Oxford handbook of memory (pp. 229-244). New York, NY: Oxford University Press) in recognition, we manipulated the opportunity to update bindings between target items and their encoding context, in young and older adults. In the first experiment we impaired the binding updating process during the encoding of items, while in the second we supported this process. The results indicated that the "Remember" responses in the younger group were specifically reduced by the impairment of the binding updating process (Exp. 1), suggesting that this ability is useful for them to encode a specific episode. Conversely, only the "Remember" responses in the older group were improved in accuracy by supporting the binding updating process (Exp. 2), suggesting that their weakness in this ability is the source of their failure to improve the accuracy of their memories. The overall results support the hypothesis that the age-related decline in episodic memory is partly due to a greater vulnerability to interference on bindings, impairing the ability to update content-context bindings as and when events occur. PMID- 27560658 TI - Immunomodulatory capacity of the local mesenchymal stem cells transplantation after severe skeletal muscle injury in female rats. AB - CONTEXT: Cell therapy technique with stem cells is a very attractive strategy for the treatment of muscle disorders. OBJECTIVE: The objective of this study was to investigate the mechanism of local transplantation of mesenchymal stem cells (MSCs) which could contribute to skeletal muscle healing. MATERIALS AND METHODS: Female rats were divided into three equal groups as the following: group 1, the negative control group (untreated group), group 2, sham-treated group, rats with muscle injuries involving volumetric muscle loss (VML) of adductor brevis muscle and injected locally with phosphate-buffered saline (PBS) 0.5 ml without stem cells after 7 d of muscle injury, group 3, treated group, rats with VML and injected locally (intramuscular) with 1.5 * 106 bone marrow MSCs suspended in PBS 0.5 ml (1) after 7 d of muscle tissue injury. All animals were sacrificed after 4 weeks of stem cell transplantation. RESULTS: In vitro culture the morphology of MSCs reached confluence and appeared as long spindle in shape on 9-14 d. Most of the cells did not express the hematopoietic cell marker, CD34 and CD45 but expressed MSCs marker CD44, CD90 and CD105. The remarkable increase of proliferating cell nuclear antigen positive nucleus was recorded in MSCs group as compared to PBS group. After 28 d of injection, administration of only PBS into the site of muscle injury caused up-regulation in the levels of interleukins IL 1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta1), interferon alpha (IFN-alpha) and down-regulate the level of IL 10 in muscular tissue comparing to the untreated control. Bone marrow MSCs + PBS injected at the site of muscle injury significantly down-regulate the inflammatory cytokines levels IL-1beta and IL-6 and TNF-alpha, TGF-beta1 and IFN alpha and up-regulate the level of IL-10. Collagen concentrations in the injured skeletal muscle estimated by enzyme-linked immuno sorbent assay and stained with Masson trichrome stain were increased with PBS group and decreased after transplantation of bone marrow MSCs in the site of injury. Muscle sections stained with H&E showed a higher number of centronucleated regenerating myofibers in the stem-cell-treated group than in the (PBS) and untreated control group. Microvasculature of skeletal muscle was decreased as demonstrated by immunostaining technique for CD34 in PBS group from untreated control. The MSCs group showed angiogenesis and marked increase of skeletal muscle microvasculature than PBS group. CONCLUSION: MSCs can modify the local immunological responses and improve muscle regeneration by suppressing of inflammatory cytokines, activating of the anti-inflammatory cytokine, restoration of muscle fibers and angiogenesis. By means of increase in TGF-beta production in response to muscle injury prevent the repair of injured fibers and increase connective tissue production (collagen fibers), thus propagating skeletal muscle weakness and fibrosis whereas MSCs + PBS injected at the site of muscle injury significantly down-regulate (TGF-beta1) and hence the level of collagen (fibrosis or scar areas). MSCs are able to block the fibrotic signaling cascade by declining TGF-beta1 and scar areas in the injured muscle. PMID- 27560657 TI - Do Changes in Current Flow as a Result of Arrays of Tidal Turbines Have an Effect on Benthic Communities? AB - Arrays of tidal energy converters have the potential to provide clean renewable energy for future generations. Benthic communities may, however, be affected by changes in current speeds resulting from arrays of tidal converters located in areas characterised by strong currents. Current speed, together with bottom type and depth, strongly influence benthic community distributions; however the interaction of these factors in controlling benthic dynamics in high energy environments is poorly understood. The Strangford Lough Narrows, the location of SeaGen, the world's first single full-scale, grid-compliant tidal energy extractor, is characterised by spatially heterogenous high current flows. A hydrodynamic model was used to select a range of benthic community study sites that had median flow velocities between 1.5-2.4 m/s in a depth range of 25-30 m. 25 sites were sampled for macrobenthic community structure using drop down video survey to test the sensitivity of the distribution of benthic communities to changes in the flow field. A diverse range of species were recorded which were consistent with those for high current flow environments and corresponding to very tide-swept faunal communities in the EUNIS classification. However, over the velocity range investigated, no changes in benthic communities were observed. This suggested that the high physical disturbance associated with the high current flows in the Strangford Narrows reflected the opportunistic nature of the benthic species present with individuals being continuously and randomly affected by turbulent forces and physical damage. It is concluded that during operation, the removal of energy by marine tidal energy arrays in the far-field is unlikely to have a significant effect on benthic communities in high flow environments. The results are of major significance to developers and regulators in the tidal energy industry when considering the environmental impacts for site licences. PMID- 27560659 TI - Low-strain heteroepitaxial nanodiamonds: fabrication and photoluminescence of silicon-vacancy colour centres. AB - Nanodiamonds with the 'diamond' 1332.5 cm(-1) Raman line as narrow as 1.8 cm(-1) have been produced by reactive ion etching in oxygen plasma of heteroepitaxial diamond particles grown by microwave plasma enhanced chemical vapour deposition (MWPECVD) on silicon. After the etching, a doublet is recorded in the zero-phonon line photoluminescence spectra of an ensemble of silicon-vacancy (SiV) centres at 10 K. Each line of the doublet is split into two lines corresponding to the optical transitions between the split excited and ground energy levels of the SiV centres. These Raman and photoluminescent features have been observed previously only in low-strain homoepitaxial diamond films and single-crystal diamond. PMID- 27560660 TI - Time to Initiation of Adjuvant Chemotherapy in Colon Cancer: Comparison of Open, Laparoscopic, and Robotic Surgery. AB - BACKGROUND: The time to initiation of adjuvant chemotherapy (TIC) can be used as a recovery parameter after surgery. The effect of laparoscopic or robotic surgery on TIC has not been thoroughly studied. This study aimed to compare the impact of open, laparoscopic, and robot-assisted surgery on TIC after colon cancer surgery. MATERIALS AND METHODS: Patients who underwent curative resection for stage II or III colon cancer between January 2007 and June 2013 and who received adjuvant chemotherapy from surgeons capable of performing open, laparoscopic, and robotic surgeries were included in this study. Patient demographics, clinicopathologic variables, and TIC were compared among the three groups. Univariate and multivariate analyses were performed to identify factors affecting TIC. RESULTS: Of the 252 patients, 40, 161, and 51 patients underwent open, laparoscopic, and robotic colectomy, respectively. The postoperative complication rate was lower in the laparoscopic and robotic groups compared to the open group (P = .002). The length of hospital stay was shorter in the laparoscopic group compared with the open and robotic groups (P < .001). Multivariate analysis revealed that the operation method was the only factor affecting TIC, with laparoscopic and robotic surgery being favorable (regression coefficient -5.1, 95% confidence interval 7.6 to -2.6; P < .001). However, there was no difference in TIC between the laparoscopic and robotic group. CONCLUSIONS: Laparoscopic and robotic surgeries were associated with shorter TIC. This study demonstrates another benefit of minimally invasive surgery with regard to early initiation of adjuvant chemotherapy. PMID- 27560661 TI - Cognitive factors affecting children's nonsymbolic and symbolic magnitude judgment abilities: A latent profile analysis. AB - Early math abilities are claimed to be linked to magnitude representation ability. Some claim that nonsymbolic magnitude abilities scaffold the acquisition of symbolic (Arabic number) magnitude abilities and influence math ability. Others claim that symbolic magnitude abilities, and ipso facto math abilities, are independent of nonsymbolic abilities and instead depend on the ability to process number symbols (e.g., 2, 7). Currently, the issue of whether symbolic abilities are or are not related to nonsymbolic abilities, and the cognitive factors associated with nonsymbolic-symbolic relationships, remains unresolved. We suggest that different nonsymbolic-symbolic relationships reside within the general magnitude ability distribution and that different cognitive abilities are likely associated with these different relationships. We further suggest that the different nonsymbolic-symbolic relationships and cognitive abilities in combination differentially predict math abilities. To test these claims, we used latent profile analysis to identify nonsymbolic-symbolic judgment patterns of 124, 5- to 7-year-olds. We also assessed four cognitive factors (visuospatial working memory [VSWM], naming numbers, nonverbal IQ, and basic reaction time [RT]) and two math abilities (number transcoding and single-digit addition abilities). Four nonsymbolic-symbolic ability profiles were identified. Naming numbers, VSWM, and basic RT abilities were differentially associated with the different ability profiles and in combination differentially predicted math abilities. Findings show that different patterns of nonsymbolic-symbolic magnitude abilities can be identified and suggest that an adequate account of math development should specify the inter-relationship between cognitive factors and nonsymbolic-symbolic ability patterns. PMID- 27560663 TI - Smoking and Secondhand Smoke Exposure at Home Were Associated with Poor Perceived Family Well-Being: Findings of FAMILY Project. AB - INTRODUCTION: To investigate the associations of cigarette smoking and secondhand (SHS) exposure at home with family well-being among Chinese adults in Hong Kong. METHODS: Telephone surveys were conducted among 3043 randomly selected adults (response rate 70%) in 2010 and 2012 to monitor family health information and tobacco use in Hong Kong. Family well-being was measured using three questions of perceived family harmony, happiness and health (3Hs) with responses ranging from 0-10 and a higher score indicating better family well-being. Smoking status, nicotine dependence, quitting behaviours and SHS exposure at home were recorded. Multiple linear regressions were used to calculate beta-coefficients for individual family 3Hs component and an overall composite score representing family well-being. RESULTS: Compared with never smokers, current smokers reported lower levels of family harmony (adjusted beta = -0.15, 95% CI: -0.35 to -0.10), happiness (adjusted beta = -0.12, 95% CI: -0.28 to -0.02), health (adjusted beta = -0.15, 95% CI: -0.30 to -0.03) and overall family well-being (adjusted beta = 0.17, 95% CI: -0.32 to -0.06). Quit attempt and intention to quit were not associated with family well-being. SHS exposure at home was associated with lower levels of family harmony (adjusted beta = -0.17, 95% CI: -0.30 to -0.07), happiness (adjusted beta = -0.19, 95% CI: -0.32 to -0.08), health (adjusted beta = -0.13, 95% CI: -0.26 to -0.03) and family well-being (adjusted beta = -0.19, 95% CI: -0.32 to -0.09). CONCLUSIONS: Smoking and SHS exposure at home were associated with the lower levels of perceived family well-being. Prospective studies are needed to confirm the results. PMID- 27560662 TI - Cigarette smoking and gastric cancer in the Stomach Cancer Pooling (StoP) Project. AB - Tobacco smoking is a known cause of gastric cancer, but several aspects of the association remain imprecisely quantified. We examined the relation between cigarette smoking and the risk of gastric cancer using a uniquely large dataset of 23 epidemiological studies within the 'Stomach cancer Pooling (StoP) Project', including 10 290 cases and 26 145 controls. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study specific ORs using random-effects models. Compared with never smokers, the ORs were 1.20 (95% CI: 1.09-1.32) for ever, 1.12 (95% CI: 0.99-1.27) for former, and 1.25 (95% CI: 1.11-1.40) for current cigarette smokers. Among current smokers, the risk increased with number of cigarettes per day to reach an OR of 1.32 (95% CI: 1.10-1.58) for smokers of more than 20 cigarettes per day. The risk increased with duration of smoking, to reach an OR of 1.33 (95% CI: 1.14-1.54) for more than 40 years of smoking and decreased with increasing time since stopping cigarette smoking (P for trend<0.01) and became similar to that of never smokers 10 years after stopping. Risks were somewhat higher for cardia than noncardia gastric cancer. Risks were similar when considering only studies with information on Helicobacter pylori infection and comparing all cases to H. pylori+ controls only. This study provides the most precise estimate of the detrimental effect of cigarette smoking on the risk of gastric cancer on the basis of individual data, including the relationship with dose and duration, and the decrease in risk following stopping smoking. PMID- 27560665 TI - Nodal Disease Burden for Early-Stage Oral Cancer. AB - Importance: Nodal disease has a significant effect on survival of patients with oral squamous cell carcinoma (OSCC). The decision for elective neck dissection for clinically node-negative (cN0) disease remains elusive. Objectives: To determine the efficacy of prophylactic neck treatment and to assess the value of commonly used clinicopathologic factors associated with nodal disease for early stage OSCC. Design, Setting, and Participants: This retrospective study from a population-based cancer registry included patients diagnosed as having OSCC from January 11, 2001, to December 24, 2007, who were identified from the British Columbia Cancer Agency Registry. Comprehensive clinicopathologic data, treatment information, and time to outcome were collected. Five-year overall survival, disease-specific survival, and cumulative incidence of regional failure (RF) were analyzed. Receiver operating characteristic curve analysis with sensitivity and specificity was used to determine the association of these covariates with RF during follow-up. Data were analyzed from January 16 to June 30, 2015. Interventions: Follow-up of patients with cN0 OSCC with or without prophylactic neck treatment (elective neck dissection [END] and or radiotherapy). Main Outcomes and Measures: Patient demographic characteristics, clinicopathologic data, treatment data, and time from the initial surgery to last follow-up, the development of RF, or death due to oral cancer or other causes. Results: Of the 469 patients with cN0 primary OSCC who underwent intent-to-cure surgery for the intraoral lesion, 447 received local excision (LE) for the primary tumor (256 men [57.3%] and 191 women [42.7%]; mean [SD] age, 63.3 [14.7] years). Patients who received prophylactic treatment of the neck (n = 125) compared with LE only (n = 322) had no survival advantage. The estimated 5-year overall and disease-specific survival rates were 61.9% (95% CI, 56.5%-67.8%) and 80.8% (95% CI, 76.1%-85.6%), respectively, for the LE-only group; 54.4% (95% CI, 45.9%-64.5%) and 73.1% (95% CI, 65%-82.3%), respectively, for the LE + END +/- radiotherapy group; and 61.7% (95% CI, 52.3%-72.8%) and 80.3% (95% CI, 72%-89.4%), respectively, for the LE + END group. Among the patients with cN0 disease receiving LE only, 89 (27.6%; 95% CI, 23%-33%) developed RF at a median time of 10.8 months, and 71 of the RFs (79.8%) developed within 30 months. Tumor depth of invasion of at least 4 mm and tumor grade of 2 or 3 showed an association with RF but had poor sensitivity and specificity. Conclusions and Relevance: Commonly used pathologic factors to decide neck dissection for cN0 OSCC are not effective and can cause overtreatment or undertreatment. The need for identification of new objective approaches for risk assessment of RF is urgent. PMID- 27560664 TI - Validation of Reference Genes for Robust qRT-PCR Gene Expression Analysis in the Rice Blast Fungus Magnaporthe oryzae. AB - The rice blast fungus causes significant annual harvest losses. It also serves as a genetically-tractable model to study fungal ingress. Whilst pathogenicity determinants have been unmasked and changes in global gene expression described, we know little about Magnaporthe oryzae cell wall remodelling. Our interests, in wall remodelling genes expressed during infection, vegetative growth and under exogenous wall stress, demand robust choice of reference genes for quantitative Real Time-PCR (qRT-PCR) data normalisation. We describe the expression stability of nine candidate reference genes profiled by qRT-PCR with cDNAs derived during asexual germling development, from sexual stage perithecia and from vegetative mycelium grown under various exogenous stressors. Our Minimum Information for Publication of qRT-PCR Experiments (MIQE) compliant analysis reveals a set of robust reference genes used to track changes in the expression of the cell wall remodelling gene MGG_Crh2 (MGG_00592). We ranked nine candidate reference genes by their expression stability (M) and report the best gene combination needed for reliable gene expression normalisation, when assayed in three tissue groups (Infective, Vegetative, and Global) frequently used in M. oryzae expression studies. We found that MGG_Actin (MGG_03982) and the 40S 27a ribosomal subunit MGG_40s (MGG_02872) proved to be robust reference genes for the Infection group and MGG_40s and MGG_Ef1 (Elongation Factor1-alpha) for both Vegetative and Global groups. Using the above validated reference genes, M. oryzae MGG_Crh2 expression was found to be significantly (p<0.05) elevated three-fold during vegetative growth as compared with dormant spores and two fold higher under cell wall stress (Congo Red) compared to growth under optimal conditions. We recommend the combinatorial use of two reference genes, belonging to the cytoskeleton and ribosomal synthesis functional groups, MGG_Actin, MGG_40s, MGG_S8 (Ribosomal subunit 40S S8) or MGG_Ef1, which demonstrated low M values across heterogeneous tissues. By contrast, metabolic pathway genes MGG_Fad (FAD binding domain containing protein) and MGG_Gapdh (Glyceraldehyde-3-phosphate dehydrogenase) performed poorly, due to their lack of expression stability across samples. PMID- 27560666 TI - Soil Water Holding Capacity Mitigates Downside Risk and Volatility in US Rainfed Maize: Time to Invest in Soil Organic Matter? AB - Yield stability is fundamental to global food security in the face of climate change, and better strategies are needed for buffering crop yields against increased weather variability. Regional- scale analyses of yield stability can support robust inferences about buffering strategies for widely-grown staple crops, but have not been accomplished. We present a novel analytical approach, synthesizing 2000-2014 data on weather and soil factors to quantify their impact on county-level maize yield stability in four US states that vary widely in these factors (Illinois, Michigan, Minnesota and Pennsylvania). Yield stability is quantified as both 'downside risk' (minimum yield potential, MYP) and 'volatility' (temporal yield variability). We show that excessive heat and drought decreased mean yields and yield stability, while higher precipitation increased stability. Soil water holding capacity strongly affected yield volatility in all four states, either directly (Minnesota and Pennsylvania) or indirectly, via its effects on MYP (Illinois and Michigan). We infer that factors contributing to soil water holding capacity can help buffer maize yields against variable weather. Given that soil water holding capacity responds (within limits) to agronomic management, our analysis highlights broadly relevant management strategies for buffering crop yields against climate variability, and informs region-specific strategies. PMID- 27560667 TI - Transmucosal Implant Placement with Submarginal Connective Tissue Graft in Area of Shallow Buccal Bone Dehiscence: A Three-Year Follow-Up Case Series. AB - The aim of the present case series study was to evaluate the short- and long-term (3 years) soft tissue stability of a surgical technique combining transmucosal implant placement with submarginal connective tissue graft (CTG) in an area of shallow buccal bone dehiscence. A sample of 20 patients were treated by positioning a transmucosal implant in an intercalated edentulous area. A CTG sutured to the inner aspect of the buccal flap was used to cover the shallow buccal bone dehiscence. Clinical evaluations were made at 6 months (T1) and 1 (T2) and 3 (T3) years after the surgery. Statistically significant increases in buccal soft tissue thickness and improvement of vertical soft tissue level were achieved at the T1, T2, and T3 follow-ups. A significant increase in keratinized tissue height was also found at T3. No significant marginal bone loss was recorded. The submarginal CTG technique was able to provide simultaneous vertical and horizontal soft tissue increases around single implants with shallow buccal bone dehiscence and no buccal mucosal recession or clinical signs of mucositis or peri-implantitis at 1 and 3 years. PMID- 27560668 TI - Comparison of Marginal Bone Changes with Internal Conus and External Hexagon Design Implant Systems: A Prospective, Randomized Study. AB - A central dental implant success criterion is the marginal bone response as measured longitudinally. Factors that influence marginal bone changes include osseous and soft tissue architecture, occlusal loading factors, implant position, implant design, and inflammatory processes. The evolution of implant design is multifactorial and includes the implant-abutment interface geometries. The primary objective of this study was to compare the proximal marginal bone changes following placement and loading of internal conus design implants (ICI) and external hex design implants (EXI) used in the treatment of posterior partial edentulism. Among 45 enrolled participants, 39 were treated with 47 ICI or 46 EXI implants using a one-stage implant protocol. Prosthetic restoration was completed after 12 weeks using stock titanium abutments and all-ceramic crowns. Follow-up visits including clinical and radiographic examinations were performed 6 months after permanent restoration and then annually for 3 years. Marginal bone level changes, papilla index scores, condition of the peri-implant mucosa, presence of complications, and participant satisfaction were evaluated. The mean marginal bone level change from implant placement to 3 years was -0.25 +/- 0.60 mm and 0.5 +/- 0.93 mm for ICI and EXI implants, respectively. The change recorded from permanent restoration to 3 years was a gain of 0.31 +/- 0.41 mm versus 0.04 +/- 0.51 mm for ICI and EXI implants, respectively (P < .05). In the evaluation of interproximal soft tissue 3 years after permanent restoration, 80% of mandibular and 66% of maxillary interproximal ICI sites received papilla scores of 2 and 3, compared with 50% of mandibular and 60% of maxillary interproximal EXI sites. No significant differences in plaque or bleeding scores were recorded. Abutment/healing abutment complications were recorded for 11 EXI versus 1 ICI participant. The vast majority (> 90%) of participants stated they were satisfied or very satisfied with their implant prosthesis and rated function and esthetics highly for both implant types after 3 years in function. Modestly greater marginal bone loss occurred at EXI implants. Further, more positive papilla scores were found between adjacent ICI implants than between adjacent EXI implants. EXI implants displayed more abutment complications than the ICI implants. The implant-abutment interface design may contribute to therapeutic outcome differences. Replacement of missing posterior teeth with unsplinted implants was successful at the implant level and as reported by the participant. PMID- 27560669 TI - Five-Year Volumetric Evaluation of Periodontally Compromised Sites Restored by Immediate Implant Restorations. AB - The aim of the present study was the retrospective evaluation of the distance of the labial hard and soft tissue margins from the implant shoulder in 24 periodontally compromised sites that were restored by immediate implant restorations. Volumetric analysis was performed 5 years postoperatively using cone beam computed tomography with limited field of view. In all cases, a labial radiopaque plate component was apparent 5 years postoperatively coronal to the implant shoulder (3.1 +/- 0.6 mm), supporting the soft tissue margin, which was extending above this level (5.2 +/- 1.1 mm). In 12 of the sites, preoperative evaluation showed that this plate was missing at the time of implant placement. PMID- 27560670 TI - Abutment-Supported Papilla: A Combined Surgical and Prosthetic Approach to Papilla Reformation. AB - Restoration of lost interdental papilla remains one of the most challenging goals for clinicians. When a single tooth is replaced with an implant, the papilla between the tooth and the implant can often be maintained or predictably reconstructed as long as the periodontal attachment and bone of the adjacent tooth is preserved. However, if the periodontal support is compromised on the neighboring natural tooth, the papilla will often be deficient or missing. This article presents a multidisciplinary treatment approach to regenerate the interdental papilla between an implant and a periodontally compromised tooth using surgical procedures and a customized abutment. Specifically, an abutment with modified subgingival contours is used to enhance support of the surgically reformed papilla. PMID- 27560671 TI - The Effect of Laser-Etched Surface Design on Soft Tissue Healing of Two Different Implant Abutment Systems: An Experimental Study in Dogs. AB - This study describes the early soft tissue morphology around two different implant systems that received either smooth or laser-etched abutments in a beagle dog model. Implants were placed in the healed mandibular molar region of eight beagle dogs and allowed to heal for 7 weeks. When the most apical aspect of the junctional epithelium (JE) was above or within the upper half of the laser-etched region, fibers were oriented perpendicular to the abutment surface. In contrast, JE positioned within the lower half of the laser-etched region or within or below the implant-abutment gap level presented fibers oriented parallel to the abutment surface. PMID- 27560672 TI - Partial Extraction Therapies (PET) Part 1: Maintaining Alveolar Ridge Contour at Pontic and Immediate Implant Sites. AB - Buccopalatal collapse of the postextraction ridge is a significant challenge in restorative and implant dentistry. A variety of ridge preservation techniques using tissue and augmentative materials have been proposed in the literature. A slightly different approach is to use the tooth itself. Root submergence has been reported in the literature for more than 4 decades, and it has been demonstrated that the submerged tooth root retains the periodontal tissues and preserves the bone in pontic sites or below dentures to retain the ridge. The socket-shield technique entails preparing a tooth root section simultaneous to immediate implant placement and has demonstrated histologic and clinical results that are highly promising to esthetic implant treatment. The pontic shield technique preserves the alveolar ridge at sites intended for pontic development where the root submergence technique is not possible. The aforementioned techniques collectively may be termed partial extraction therapies (PET), a term newly introduced into the literature and clinical environment. This article is a review of these ridge preservation therapies, providing a classification and a guide to their application. PMID- 27560673 TI - Reconstruction of Extended and Morphologically Varied Alveolar Ridge Defects with the Titanium Mesh Technique: Clinical and Dental Implants Outcomes. AB - A sample of 24 patients with varied morphologic defects were treated with 34 titanium meshes and particulate bone and rehabilitated at least 8 to 9 months thereafter with the placement of 88 implants. Of the 34 meshes, 4 had to be removed before implant placement (11.76% total failure) and 20 were exposed due to soft tissue dehiscence (58.82% of complications): 4 (11.77%) prematurely (within 4 to 6 weeks) and 16 (47.05%) delayed (after 4 to 6 weeks), with no compromise in implant placement. None of the 88 implants was lost (100% implant survival), and 15 demonstrated increased bone loss, yielding a cumulative implant success rate of 82.9%. This technique appears useful in treating extended and morphologically varied alveolar defects. PMID- 27560674 TI - A Classification System for Peri-implant Diseases and Conditions. AB - Peri-implant bone levels are influenced by pathologic and nonpathologic conditions. The understanding of peri-implant disease has evolved over the past several decades, and the classification of peri-implantitis has been limited to descriptions of disease progression or those involving soft and/or hard tissues (peri-implant mucositis or peri-implantitis). However, no classification system has been established based on etiology. The objective of this study was to identify various etiologies for peri-implantitis and to establish a classification system based on the pathogenesis. The results indicate that the majority of bone loss was related to biofilm, followed by iatrogenic factors, exogenous irritants, absence of keratinized tissue, and extrinsic pathology. The proposed classification system will allow the clinician to properly diagnose peri implant diseases in relation to etiology. These conditions may respond differently to applied therapies. PMID- 27560675 TI - Custom Titanium Ridge Augmentation Matrix (CTRAM): A Case Report. AB - This is a case report of a custom titanium ridge augmentation matrix (CTRAM). Using cone beam computed tomography (CBCT), a custom titanium space-maintaining device was developed. Alveolar ridges were virtually augmented, a matrix was virtually designed, and the CTRAM was additively manufactured with titanium (Ti6Al4V). Two cases are presented that resulted in sufficient increased horizontal bone volume with successful dental implant placement. The CTRAM design allows for preoperative planning for increasing alveolar ridge dimensions to support dental implants, reduces surgical time, and prevents the need for a second surgical site to gain sufficient alveolar ridge bone volume for dental implant therapy. PMID- 27560676 TI - Efficacy of Adjunctive Er, Cr:YSGG Laser Application Following Scaling and Root Planing in Periodontally Diseased Patients. AB - The application of laser as a monotherapy has been shown to reduce probing pocket depths and increase clinical attachment levels after treatment of patients suffering from chronic periodontitis. Its controversial use as an adjunct to scaling and root planing (SRP) is discussed. The present study aimed to evaluate the efficacy of adjunctive Er, Cr:YSGG laser application following conventional SRP. A total of 30 patients with chronic periodontitis were enrolled in the study. The quadrants of each patient were allocated to either SRP or SRP + laser. A total of 3,654 sites with pocket depths >= 4 mm were treated and evaluated at 6 weeks and 6 months postoperatively with respect to attachment gain. Both therapies resulted in improved probing pocket depths and clinical attachment levels. The adjunctive application of Er, Cr:YSGG laser following SRP did not improve probing pocket depth or attachment level compared with SRP alone. PMID- 27560677 TI - Human Histologic and Radiographic Evidence of Bone Formation in a Previously Infected Maxillary Sinus Graft Following Debridement Without Regrafting: A Case Report. AB - The aim of this case report was to evaluate the histologic and radiographic new bone formation following maxillary sinus reentry surgery without a bone graft. A 61-year-old woman was referred with a failure of a sinus augmentation procedure. A reentry procedure was performed to retreat the sinus complication. The procedure involved removal of the bone graft plus debridement of the sinus. No additional bone graft material was used. A cone beam computed tomography scan was taken 6 months following the reentry procedure. During implant placement surgery, a core biopsy specimen was retrieved, stored, and prepared to obtain thin ground undecalcified sections. The histologic and radiographic analysis showed formation of new bone at the time of implant placement. At 18 months following implant placement, successful evidence of integration was determined by implant stability and radiographs. Space maintained by the previously elevated sinus membrane at the time of sinus reentry was sufficient to induce formation of bone without regrafting. However, more cases involving survival of implants placed in augmented sinuses without the use of bone grafts at the time of reentry are needed to confirm the results of this case report study. PMID- 27560678 TI - In Vitro Assessment of Primary Stability of BoneTrust Sinus Implant Design. AB - The aim of this study was to analyze the primary stability of BoneTrust Sinus implants (BTSIs), which are intended to enable higher primary stability by their special design with reduced thread section in cases of reduced vertical bone availability, in comparison with standard BoneTrust implants (SBTIs) in vitro. A bone window 3 cm in length, 4 cm in width, and 3 cm in depth, resembling the maxillary bone window of the lateral sinus wall with 4 mm of residual bone height, was prepared at the dorsal side of freshly slaughtered bovine ribs. One single BTSI and a single SBTI with the same diameter (4 or 5 mm) were placed in each window. After implant placement, the implant stability quotient (ISQ) was measured by using resonance frequency analysis with an Osstell device. A total of 88 implants were placed. ISQ values varied between 63 and 84. Among the implants with 4-mm diameter, all BTSIs showed higher ISQ values compared with SBTIs. One way analysis of variance showed a significant difference between BTSIs/SBTIs (P < .05). BTSIs with 4-mm diameter showed statistically higher values compared to BTSIs with 5-mm diameter (P < .05). Among the implants with 5-mm diameter, all SBTIs showed higher ISQ values compared to BTSIs but there was no significant difference. The use of 4-mm-diameter BTSIs could present higher ISQ values during simultaneous implant placement in conjunction with lateral sinus floor augmentation. PMID- 27560679 TI - The Effect of Inital-Phase Bone Remodeling on Implant Wound Healing. AB - This case series aimed to investigate the initial-phase bone remodeling during implant wound healing and to discuss the possible contributing factors. A total of 11 implants with polished collars were placed in premaxillary regions via flapless approach with the aid of computer technology. After 15 months of follow up, the results suggested that the presence of polished collars triggered bone resorption via a bone remodeling mechanism. The overall vertical crestal resorption was 0.78 +/- 0.46 mm on average. This initial-phase bone remodeling primarily occurred within the first 3 months postoperatively. The slightly exposed polished collar may not worsen crestal bone level. PMID- 27560680 TI - Bone Response to Four Dental Implants with Different Surface Topographies: A Histologic and Histometric Study in Minipigs. AB - This study evaluated four implant surfaces in a minipig model: (1) Kohno Straight dual-engineered surface (DES) (Sweden & Martina); (2) SLActive (Straumann); (3) SM Biotite-H coated with Brushite (DIO); and (4) UF hybrid sandblasted and acid etched (HAS) (DIO). The surfaces presented different topographic features on the macro-, micro-, and nanoscales. After 12 weeks in vivo, significant differences were observed in bone-to-implant contact. UF HAS, presenting moderate microroughness and high nanoroughness, showed some advantage compared to nanorough SM Biotite-H and SLActive. A more pronounced difference was observed between UF HAS and Kohno Straight DES, characterized by a nanosmooth surface. Newly formed bone was observed around all surfaces. PMID- 27560681 TI - Evaluation of Dental Shade Guide Variability Using Cross-Polarized Photography. AB - This study evaluated color variability in the A hue between the VITA Classical (VITA Zahnfabrik) shade guide and four other VITA-coded ceramic shade guides using a Canon EOS 60D camera and software (Photoshop CC, Adobe). A total of 125 photographs were taken, 5 per shade tab for each of 5 shades (A1 to A4) from the following shade guides: VITA Classical (control), IPS e.max Ceram (Ivoclar Vivadent), IPS d.SIGN (Ivoclar Vivadent), Initial ZI (GC), and Creation CC (Creation Willi Geller). Photos were processed with Adobe Photoshop CC to allow standardized evaluation of hue, chroma, and value between shade tabs. None of the VITA-coded shade tabs fully matched the VITA Classical shade tab for hue, chroma, or value. The VITA-coded shade guides evaluated herein showed an overall unmatched shade in all tabs when compared with the control, suggesting that shade selection should be made using the guide produced by the manufacturer of the ceramic intended for the final restoration. PMID- 27560682 TI - Effect of Simplified One-Step Drilling Protocol on Osseointegration. AB - This study was designed to compare the combined effect of two different drilling techniques (conventional expansion and one-step) and four different implant geometries in a beagle dog model. The nondecalcified bone-implant samples underwent histologic/metric analysis at 2 and 6 weeks. Morphologic analysis showed similarities between different drilling technique groups and implant geometries. Histomorphometric parameters, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) were analyzed, and no statistical difference between drilling groups and/or implant geometry was found. Time was the only variable that affected BIC and BAFO, suggesting that the two protocols are equally biocompatible and osseoconductive. PMID- 27560683 TI - Clinical Use of Laser-Microtextured Abutments: A Case Series. AB - This article discusses the clinical use of laser-microtextured abutments on dental implant restorations. Four cases are presented, each using one of the four commercially available laser-microtextured abutment styles. Numerous preclinical and clinical studies have shown the positive effects of laser microtexturing on the implant platform in limiting crestal bone loss and benefiting soft tissue stability. Other histologic studies of laser microtexturing on the implant abutment have demonstrated the ability of this specific feature to block epithelial downgrowth and provide a functional connective tissue attachment to the abutment surface. Other abutment designs, styles, and materials have only demonstrated a soft tissue seal with epithelial adhesion and a circular ring of connective tissue fibers around the abutment without direct contact. This article presents clinical and radiographic case examples from a private practice perspective on the longterm successful use of microtextured abutments with respect to crestal bone levels, exceptional soft tissue health, and stability with minimal sulcular depth. PMID- 27560684 TI - Correction: A Novel Top-k Strategy for Influence Maximization in Complex Networks with Community Structure. AB - [This corrects the article DOI: 10.1371/journal.pone.0145283.]. PMID- 27560685 TI - Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues. AB - The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia. Kidney endothelium (ciGENC) showed higher uptake of these nanoparticles than brain endothelium (hCMEC/D3), reflecting their biodistribution in vivo. Nanoparticle uptake and subcellular localisation was quantified by transmission electron microscopy. The rate of internalisation was approximately 4x higher in kidney endothelium than brain endothelium. Vesicular endocytosis was approximately 4x greater than cytosolic uptake in both cell types, and endocytosis was blocked by metabolic inhibition, whereas cytosolic uptake was energy-independent. The cellular basis for the different rates of internalisation was investigated. Morphologically, both endothelia had similar profiles of vesicles and cell volumes. However, the rate of endocytosis was higher in kidney endothelium. Moreover, the glycocalyces of the endothelia differed, as determined by lectin-binding, and partial removal of the glycocalyx reduced nanoparticle uptake by kidney endothelium, but not brain endothelium. This study identifies tissue-specific properties of vascular endothelium that affects their interaction with nanoparticles and rate of transport. PMID- 27560686 TI - Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model. AB - Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the optimization of acquisition protocols for preclinical and clinical dMRI studies on the spinal cord. PMID- 27560687 TI - Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study. AB - OBJECTIVE: Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. RESEARCH DESIGN AND METHODS: We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged >=18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. RESULTS: Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c >=48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7-87.8) and 98.7% specificity (95%CI 97.9-99.4) (AUC 0.94 [95%CI 0.89-1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6-99.8], specificity 92.0% [95%CI: 90.3-93.7]). CONCLUSIONS: In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa. PMID- 27560690 TI - Understanding and Treating Myopia: Yesterday, Today, and Tomorrow. PMID- 27560688 TI - Development of Germline-Humanized Antibodies Neutralizing Botulinum Neurotoxin A and B. AB - Botulinum neurotoxins (BoNTs) are counted among the most toxic substances known and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. To date, 7 serologically distinct serotypes of BoNT (serotype A-G) are known. Due to the high toxicity of BoNTs the Centers for Disease Control and Prevention (CDC) have classified BoNTs as category A agent, including the six biological agents with the highest potential risk of use as bioweapons. Well tolerated antibodies neutralizing BoNTs are required to deal with the potential risk. In a previous work, we described the development of scFv and scFv-Fc (Yumab) from macaque origin (Macaca fascicularis) neutralizing BoNT/A and B by targeting the heavy and light chain of each serotype. In the present study, we humanized the macaque antibodies SEM120-IIIC1 (anti-BoNT/A light chain), A1HC38 (anti-BoNT/A heavy chain), BLC3 (anti-BoNT/B light chain) and B2-7 (anti-BoNT/B heavy chain) by germline-humanization to obtain a better potential immunotolerance in humans. We increased the Germinality Index (GI) of SEM120-IIIC1 to 94.5%, for A1HC38, to 95% for BLC3 and to 94.4% for B2-7. Furthermore, the neutralization efficacies of the germline-humanized antibodies were analyzed in lethal and non-lethal in vivo mouse assays as full IgG. The germline-humanized IgGs hu8SEM120-IIIC1, hu8A1HC38, hu8BLC3 and hu8B2-7 were protective in vivo, when anti-heavy and anti-light chain antibodies were combined. The synergistic effect and high humanness of the selected IgGs makes them promising lead candidates for further clinical development. PMID- 27560691 TI - The Possible Role of Peripheral Refraction in Development of Myopia. AB - Recent longitudinal studies do not support the current theory of relative peripheral hyperopia causing myopia. The theory is based on misunderstanding of the Hoogerheide et al. article of 1971, which actually found relative peripheral hyperopia to be present after, rather than before, myopia development. The authors present two alternative theories of the role of peripheral refraction in the development and progression of myopia. The one for which most detail is given is based on cessation of ocular growth when the periphery is at an emmetropic stage as determined by equivalent blur of the two line foci caused by oblique astigmatism. This paper is based on an invited commentary on the role of lens treatments in myopia from the 15th International Myopia Conference in Wenzhou, China in September 2015. PMID- 27560692 TI - Animal Studies and the Mechanism of Myopia-Protection by Light? AB - Epidemiological studies have demonstrated that spending time outdoors during your childhood is protective against the development of myopia. It has been hypothesized that this protective effect is associated with light-induced increases in retinal dopamine levels, a critical neuromodulator that has long been postulated to be involved in the regulation of ocular growth. This paper, along with the paper entitled "What do animal studies tell us about the mechanism of myopia-protection by light?" discusses the evidence provided by animal models for this hypothesis. PMID- 27560694 TI - Correction: Secondary Solid Organ Neoplasm in Patients with Acute Lymphoblastic Leukemia: A Nationwide Population-Based Study in Taiwan. AB - [This corrects the article DOI: 10.1371/journal.pone.0152909.]. PMID- 27560695 TI - Cytotoxic and Antibacterial Preussomerins from the Mangrove Endophytic Fungus Lasiodiplodia theobromae ZJ-HQ1. AB - Two new chlorinated preussomerins, chloropreussomerins A and B (1 and 2), together with nine known preussomerin analogues, 3-11, were obtained from the endophytic fungus Lasiodiplodia theobromae ZJ-HQ1. Their structures were elucidated by a combination of spectroscopic analyses. The absolute configurations of 1 and 2 were both determined by single-crystal X-ray diffraction using Cu Kalpha radiation. Chloropreussomerins A and B (1 and 2) are the first chlorinated compounds in the preussomerin family, and preussomerin M (3) is reported for the first time as a natural product. Compounds 1 and 2 showed potent in vitro cytotoxicity against A549 and MCF-7 human cancer cell lines, with IC50 values ranging from 5.9 to 8.9 MUM, and compounds 4-7 exhibited significant bioactivity against A549, HepG2, and MCF-7 human cancer cell lines, with IC50 values of 2.5-9.4 MUM. In the antibacterial assay, compounds 1, 2, 5-7, and 11 exhibited significant activities against Staphylococcus aureus, with MIC values between 1.6 and 13 MUg/mL. PMID- 27560696 TI - How Many Fish Need to Be Measured to Effectively Evaluate Trawl Selectivity? AB - The aim of this study was to provide practitioners working with trawl selectivity with general and easily understandable guidelines regarding the fish sampling effort necessary during sea trials. In particular, we focused on how many fish would need to be caught and length measured in a trawl haul in order to assess the selectivity parameters of the trawl at a designated uncertainty level. We also investigated the dependency of this uncertainty level on the experimental method used to collect data and on the potential effects of factors such as the size structure in the catch relative to the size selection of the gear. We based this study on simulated data created from two different fisheries: the Barents Sea cod (Gadus morhua) trawl fishery and the Mediterranean Sea multispecies trawl fishery represented by red mullet (Mullus barbatus). We used these two completely different fisheries to obtain results that can be used as general guidelines for other fisheries. We found that the uncertainty in the selection parameters decreased with increasing number of fish measured and that this relationship could be described by a power model. The sampling effort needed to achieve a specific uncertainty level for the selection parameters was always lower for the covered codend method compared to the paired-gear method. In many cases, the number of fish that would need to be measured to maintain a specific uncertainty level was around 10 times higher for the paired-gear method than for the covered codend method. The trends observed for the effect of sampling effort in the two fishery cases investigated were similar; therefore the guidelines presented herein should be applicable to other fisheries. PMID- 27560697 TI - Interventions to increase or decrease the length of primary care physicians' consultation. AB - BACKGROUND: Observational studies have shown differences in process and outcome between the consultations of primary care physicians whose average consultation lengths differ. These differences may be due to self selection. This is the first update of the original review. OBJECTIVES: To assess the effects of interventions to alter the length of primary care physicians' consultations. SEARCH METHODS: We searched the following electronic databases until 4 January 2016: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). SELECTION CRITERIA: Randomised controlled trials and non-randomised controlled trials of interventions to alter the length of primary care physicians' consultations. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of included studies using agreed criteria and resolved disagreements by discussion. We attempted to contact authors of primary studies with missing data. Given the heterogeneity of studies, we did not conduct a meta-analysis. We assessed the certainty of the evidence for the most important outcomes using the GRADE approach and have presented the results in a narrative summary. MAIN RESULTS: Five studies met the inclusion criteria. All were conducted in the UK, and tested short-term changes in the consultation time allocated to each patient. Overall, our confidence in the results was very low; most studies had a high risk of bias, particularly due to non-random allocation of participants and the absence of data on participants' characteristics and small sample sizes. We are uncertain whether altering appointment length increases primary care consultation length, number of referrals and investigations, prescriptions, or patient satisfaction based on very low-certainty evidence. None of the studies reported on the effects of altering the length of consultation on resources used. AUTHORS' CONCLUSIONS: We did not find sufficient evidence to support or refute a policy of altering the lengths of primary care physicians' consultations. It is possible that these findings may change if high-quality trials are reported in the future. Further trials are needed that focus on health outcomes and cost-effectiveness. PMID- 27560700 TI - Erratum. PMID- 27560699 TI - Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects. AB - The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV. PMID- 27560698 TI - Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape. AB - The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics. PMID- 27560701 TI - DNA-binding and repressor function are prerequisites for the turnover of the tomato heat stress transcription factor HsfB1. AB - HsfB1 is a central regulator of heat stress (HS) response and functions dually as a transcriptional co-activator of HsfA1a and a general repressor in tomato. HsfB1 is efficiently synthesized during the onset of HS and rapidly removed in the course of attenuation during the recovery phase. Initial results point to a complex regime modulating HsfB1 abundance involving the molecular chaperone Hsp90. However, the molecular determinants affecting HsfB1 stability needed to be established. We provide experimental evidence that DNA-bound HsfB1 is efficiently targeted for degradation when active as a transcriptional repressor. Manipulation of the DNA-binding affinity by mutating the HsfB1 DNA-binding domain directly influences the stability of the transcription factor. During HS, HsfB1 is stabilized, probably due to co-activator complex formation with HsfA1a. The process of HsfB1 degradation involves nuclear localized Hsp90. The molecular determinants of HsfB1 turnover identified in here are so far seemingly unique. A mutational switch of the R/KLFGV repressor motif's arginine and lysine implies that the abundance of other R/KLFGV type Hsfs, if not other transcription factors as well, might be modulated by a comparable mechanism. Thus, we propose a versatile mechanism for strict abundance control of the stress-induced transcription factor HsfB1 for the recovery phase, and this mechanism constitutes a form of transcription factor removal from promoters by degradation inside the nucleus. PMID- 27560703 TI - Electrocatalysis of CO2 Reduction in Brush Polymer Ion Gels. AB - The electrochemical characterization of brush polymer ion gels containing embedded small-molecule redox-active species is reported. Gels comprising PS-PEO PS triblock brush polymer, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIm-TFSI), and some combination of ferrocene (Fc), cobaltocenium (CoCp2(+)), and Re(bpy)(CO)3Cl (1) exhibit diffusion controlled redox processes with diffusion coefficients approximately one-fifth of those observed in neat BMIm-TFSI. Notably, 1 dissolves homogeneously in the interpenetrating matrix domain of the ion gel and displays electrocatalytic CO2 reduction to CO in the gel. The catalytic wave exhibits a positive shift versus Fc(+/0) compared with analogous nonaqueous solvents with a reduction potential 450 mV positive of onset and 90% Faradaic efficiency for CO production. These materials provide a promising and alternative approach to immobilized electrocatalysis, creating numerous opportunities for application in solid-state devices. PMID- 27560702 TI - Pulmonary pharmacodynamics of an anti-GM-CSFRalpha antibody enables therapeutic dosing that limits exposure in the lung. AB - Pulmonary alveolar proteinosis is associated with impaired alveolar macrophage differentiation due to genetic defects in the granulocyte macrophage colony stimulating factor (GM-CSF) axis or autoantibody blockade of GM-CSF. The anti-GM CSFRalpha antibody mavrilimumab has shown clinical benefit in patients with rheumatoid arthritis, but with no accompanying pulmonary pathology observed to date. We aimed to model systemic versus pulmonary pharmacodynamics of an anti-GM CSFRalpha antibody to understand the pharmacology that contributes to this therapeutic margin. Mice were dosed intraperitoneal with anti-GM-CSFRalpha antibody, and pharmacodynamics bioassays for GM-CSFRalpha inhibition performed on blood and bronchoalveolar lavage (BAL) cells to quantify coverage in the circulation and lung, respectively. A single dose of 3 mg/kg of the anti-GM CSFRalpha antibody saturated the systemic cellular pool, but dosing up to 10 times higher had no effect on the responsiveness of BAL cells to GM-CSF. Continued administration of this dose of anti-GM-CSFRalpha antibody for 7 consecutive days also had no inhibitory effect on these cells. Partial inhibition of GM-CSFRalpha function on cells from the BAL was only observed after dosing for 5 or 7 consecutive days at 30 mg/kg, 10-fold higher than the proposed therapeutic dose. In conclusion, dosing with anti-GM-CSFRalpha antibody using regimes that saturate circulating cells, and have been shown to be efficacious in inflammatory arthritis models, did not lead to complete blockade of the alveolar macrophages response to GM-CSF. This suggests a significant therapeutic window is possible with GM-CSF axis inhibition. PMID- 27560704 TI - Sleep extension increases IGF-I concentrations before and during sleep deprivation in healthy young men. AB - Sleep deprivation is known to suppress circulating trophic factors such as insulin-like growth factor (IGF)-I and brain-derived neurotrophic factor (BDNF). This experiment examined the effect of an intervention involving 6 nights of extended sleep before total sleep deprivation on this catabolic profile. In a randomized crossover design, 14 young men (age range: 26-37 years) were either in an extended (EXT; time in bed: 2100-0700 h) or habitual (HAB: 2230-0700 h) sleep condition, followed by 3 days in the laboratory with blood sampling at baseline (B), after 24 h of sleep deprivation (24h-SD), and after 1 night of recovery sleep (R). In the EXT condition compared with the HAB condition, free IGF-I levels were significantly higher at B, 24h-SD, and R (P < 0.001), and those of total IGF-I at B and 24h-SD (P < 0.05). EXT did not influence growth hormone, IGF binding protein 3, BDNF, insulin, and glucose levels. The only effect of 24 h of sleep deprivation was for insulin levels, which were significantly higher after R compared with B. In a healthy adult, additional sleep over 1 week increased blood concentrations of the anabolic factor IGF-I before and during 24 h of sleep deprivation and after the subsequent recovery night without effects on BDNF. With further research, these findings may prove to be important in guiding effective lifestyle modifications to limit physical or cognitive deficits associated with IGF-I decrease with age. PMID- 27560705 TI - Where is God in my dying? A qualitative investigation of faith reflections among hospice patients in a secularized society. AB - Despite increased focus on the role of spiritual care in palliative care, there is limited knowledge about spirituality/religiosity among dying patients in secularized cultures such as Denmark. This study aims through semi-structured interviews with Danish hospice patients and participant observation to elucidate how hospice patients reflect and act upon their potential faith. The results demonstrate three dimensions of faith: (1) "Knowing" (cognition), (2) "doing" (praxis) and (3) "being" (meaning). The article concludes that most patients had a hesitant, but according to their situation, important faith although it was not something they knew much about, let alone discussed or practiced much. PMID- 27560706 TI - Anode-Engineered Protonic Ceramic Fuel Cell with Excellent Performance and Fuel Compatibility. AB - Directly utilizing hydrocarbon fuels, particularly methane, is advantageous yet challenging in high-performance protonic ceramic fuel cells. In this work, this technological hurdle is well addressed by selective deposition of secondary electrocatalysts within the porous Ni-cermet anode. This novel strategy sheds light on the development of multifunctional porous structures for energy and catalysis applications. PMID- 27560707 TI - Dual structure evolution of a Ag(i) supramolecular framework triggered by anion exchange: replacement of terminal ligand and switching of network interpenetration degree. AB - A 3-fold interpenetrated Ag(i) coordination framework can exhibit dual structure evolution behaviours driven by distinct anion-exchange courses in which irreversible single-crystal to single-crystal transformation occurs, resulting in a switching of network interpenetration degree (from 3-fold to 2-fold). PMID- 27560708 TI - Attenuation of graft-versus-host-disease in NOD scid IL-2Rgamma(-/-) (NSG) mice by ex vivo modulation of human CD4(+) T cells. AB - NOD.Cg-Prkdc(scid) IL-2rg(tm1Wjl) /SzJ (NSG) mice are a valuable tool for studying Graft-versus-Host-Disease (GvHD) induced by human immune cells. We used a model of acute GvHD by transfer of human peripheral blood mononuclear cells (PBMCs) into NSG mice. The severity of GvHD was reflected by weight loss and was associated with engraftment of human cells and the expansion of leukocytes, particularly granulocytes and monocytes. Pre-treatment of PBMCs with the anti human CD4 antibody MAX.16H5 IgG1 or IgG4 attenuated GvHD. The transplantation of 2 * 10(7) PBMCs without anti-human CD4 pre-treatment induced a severe GvHD (0% survival). In animals receiving 2 * 10(7) PBMCs pre-incubated with MAX.16H5 IgG1 or IgG4, GvHD development was reduced and survival was increased. Immune reconstitution was measured by flow cytometry and confirmed for human leukocytes (CD45), CD3(+) /CD8(+) cytotoxic T cells and CD3(+) /CD4(+) T helper cells. Human B cells (CD19) and monocytes (CD14) could not be detected. Histopathological analysis (TUNEL assay) of the gut of recipient animals showed significantly less apoptotic crypt cells in animals receiving a MAX.16H5 IgG1 pre-incubated graft. These findings indicate that pre-incubation of an allogeneic graft with an anti human CD4 antibody may decrease the frequency and severity of GvHD after hematopoietic stem cell transplantation (HSCT) and the need of conventional immunosuppressive drugs. Moreover, this approach most probably provides a safer HSCT that must be confirmed in appropriate clinical trials in the future. (c) 2016 International Society for Advancement of Cytometry. PMID- 27560709 TI - Histone Deacetylase Inhibitory Approaches for the Management of Osteoarthritis. AB - This commentary highlights the article by Makki and Haqqi that proposes the use of vorinostat as a therapeutic agent for the management of osteoarthritis. PMID- 27560710 TI - Understanding Lung Development, Injury, and Repair. AB - This Editorial introduces the Lung Ontogeny and Injury Theme Issue, which provides critical insights into lung development, injury, and repair as well as key pulmonary diseases. PMID- 27560711 TI - Morphology-Induced Defects Enhance Lipid Transfer Rates. AB - Molecular transfer between nanoparticles has been considered to have important implications regarding nanoparticle stability. Recently, the interparticle spontaneous lipid transfer rate constant for discoidal bicelles was found to be very different from spherical, unilamellar vesicles (ULVs). Here, we investigate the mechanism responsible for this discrepancy. Analysis of the data indicates that lipid transfer is entropically favorable, but enthalpically unfavorable with an activation energy that is independent of bicelle size and long- to short-chain lipid molar ratio. Moreover, molecular dynamics simulations reveal a lower lipid dissociation energy cost in the vicinity of interfaces ("defects") induced by the segregation of the long- and short-chain lipids in bicelles; these defects are not present in ULVs. Taken together, these results suggest that the enhanced lipid transfer observed in bicelles arises from interfacial defects as a result of the hydrophobic mismatch between the long- and short-chain lipid species. Finally, the observed lipid transfer rate is found to be independent of nanoparticle stability. PMID- 27560712 TI - Incorporation of silicone oil into elastomers enhances barnacle detachment by active surface strain. AB - Silicone-oil additives are often used in fouling-release silicone coatings to reduce the adhesion strength of barnacles and other biofouling organisms. This study follows on from a recently reported active approach to detach barnacles, which was based on the surface strain of elastomeric materials, by investigating a new, dual-action approach to barnacle detachment using Ecoflex(r)-based elastomers incorporated with poly(dimethylsiloxane)-based oil additives. The experimental results support the hypothesis that silicone-oil additives reduce the amount of substratum strain required to detach barnacles. The study also de coupled the two effects of silicone oils (ie surface-activity and alteration of the bulk modulus) and examined their contributions in reducing barnacle adhesion strength. Further, a finite element model based on fracture mechanics was employed to qualitatively understand the effects of surface strain and substratum modulus on barnacle adhesion strength. The study demonstrates that dynamic substratum deformation of elastomers with silicone-oil additives provides a bifunctional approach towards management of biofouling by barnacles. PMID- 27560713 TI - Building quality mHealth for low resource settings. AB - In low- and middle-income countries (LMIC), community health care workers (CHCW) are the primary point of care for millions of people. Mobile phone health applications (mHealth app) are the preferred technology platform to deliver clinical support to CHCW. In LMIC, limited regulatory oversight exists to guide quality and safety for medical devices, including mHealth. During the development of a mHealth app to assist CHCW with patient assessment and clinical diagnosis in rural South Africa, we applied human-centred design (HCD) and a bioethics consultation. The HCD approach enabled us to develop a mHealth app that responded to the needs and capacities of CHCW. The bioethics consultation prompted early consideration of safety concerns, social implications of our mHealth app and our technology's impact on the CHCW-patient relationship. In this study, we found that combining a HCD approach with bioethics consultation improved the design quality and reduced safety concerns for our mHealth app. PMID- 27560714 TI - MCL-1 is required throughout B-cell development and its loss sensitizes specific B-cell subsets to inhibition of BCL-2 or BCL-XL. AB - Pro-survival BCL-2 family members protect cells from programmed cell death that can be induced by multiple internal or external cues. Within the haematopoietic lineages, the BCL-2 family members BCL-2, BCL-XL and MCL-1 are known to support cell survival but the individual and overlapping roles of these pro-survival BCL 2 proteins for the persistence of individual leukocyte subsets in vivo has not yet been determined. By combining inducible knockout mouse models with the BH3 mimetic compound ABT-737, which inhibits BCL-2, BCL-XL and BCL-W, we found that dependency on MCL-1, BCL-XL or BCL-2 expression changes during B-cell development. We show that BCL-XL expression promotes survival of immature B cells, expression of BCL-2 is important for survival of mature B cells and long lived plasma cells (PC), and expression of MCL-1 is important for survival throughout B-cell development. These data were confirmed with novel highly specific BH3-mimetic compounds that target either BCL-2, BCL-XL or MCL-1. In addition, we observed that combined inhibition of these pro-survival proteins acts in concert to delete specific B-cell subsets. Reduced expression of MCL-1 further sensitized immature as well as transitional B cells and splenic PC to loss of BCL-XL expression. More markedly, loss of MCL-1 greatly sensitizes PC populations to BCL-2 inhibition using ABT-737, even though the total wild-type PC pool in the spleen is not significantly affected by this drug and the bone marrow (BM) PC population only slightly. Combined loss or inhibition of MCL-1 and BCL-2 reduced the numbers of established PC >100-fold within days. Our data suggest that combination treatment targeting these pro-survival proteins could be advantageous for treatment of antibody-mediated autoimmune diseases and B-cell malignancies. PMID- 27560717 TI - Isolated myeloid sarcoma. PMID- 27560715 TI - NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II. AB - Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP is caused by NF-kappaB essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as a crucial component mediating the recruitment of the IkappaB-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation of the pro-survival NF-kappaB response. However, recent studies have suggested that gene activation and cell death inhibition are two independent activities of NEMO. Here we describe that cells expressing the IP associated NEMO-A323P mutant had completely abrogated TNF-induced NF-kappaB activation, but retained partial antiapoptotic activity and exhibited high sensitivity to death by necroptosis. We found that robust caspase activation in NEMO-deficient cells is concomitant with RIPK3 recruitment to the apoptosis mediating complex. In contrast, cells expressing the ubiquitin-binding mutant NEMO-A323P did not recruit RIPK3 to complex II, an event that prevented caspase activation. Hence NEMO, independently from NF-kappaB activation, represents per se a key component in the structural and functional dynamics of the different TNF R1-induced complexes. Alteration of this process may result in differing cellular outcomes and, consequently, also pathological effects in IP patients with different NEMO mutations. PMID- 27560716 TI - Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells. AB - Alpha1,2-fucosyltransferases, FUT1 and FUT2, which transfer fucoses onto the terminal galactose of N-acetyl-lactosamine via alpha1,2-linkage have been shown to be highly expressed in various types of cancers. A few studies have shown the involvement of FUT1 substrates in tumor cell proliferation and migration. Lysosome-associated membrane protein 1, LAMP-1, has been reported to carry alpha1,2-fucosylated Lewis Y (LeY) antigens in breast cancer cells, however, the biological functions of LeY on LAMP-1 remain largely unknown. Whether or not its family member, LAMP-2, displays similar modifications and functions as LAMP-1 has not yet been addressed. In this study, we have presented evidence supporting that both LAMP-1 and 2 are substrates for FUT1, but not FUT2. We have also demonstrated the presence of H2 and LeY antigens on LAMP-1 by a targeted nanoLC MS(3) and the decreased levels of fucosylation on LAMP-2 by MALDI-TOF analysis upon FUT1 knockdown. In addition, we found that the expression of LeY was substantial in less invasive ER+/PR+/HER- breast cancer cells (MCF-7 and T47D) but negligible in highly invasive triple-negative MDA-MB-231 cells, of which LeY levels were correlated with the levels of LeY carried by LAMP-1 and 2. Intriguingly, we also observed a striking change in the subcellular localization of lysosomes upon FUT1 knockdown from peripheral distribution of LAMP-1 and 2 to a preferential perinuclear accumulation. Besides that, knockdown of FUT1 led to an increased rate of autophagic flux along with diminished activity of mammalian target of rapamycin complex 1 (mTORC1) and enhanced autophagosome-lysosome fusion. This may be associated with the predominantly perinuclear distribution of lysosomes mediated by FUT1 knockdown as lysosomal positioning has been reported to regulate mTOR activity and autophagy. Taken together, our results suggest that downregulation of FUT1, which leads to the perinuclear localization of LAMP-1 and 2, is correlated with increased rate of autophagic flux by decreasing mTOR signaling and increasing autolysosome formation. PMID- 27560719 TI - The Role of Genetic Testing in the Selection of Therapy for Breast Cancer: A Review. AB - Importance: The application of next-generation sequencing (NGS) genomic testing for somatic mutations in breast oncology has been slower than anticipated due to issues with clinical applicability and natural heterogeneity of breast cancer. This review summarizes the state of the field and considers approaches for more effective implementation. Observations: While there is an emerging role for germline genetic testing potentially predicting sensitivity to platinum salts and PARP inhibitors, the data regarding somatic mutation for prediction of drug sensitivity remains controversial. Currently, there are no guidelines or regulatory approvals for genomic somatic tumor mutation testing to direct therapy. However, some small populations show promise, such as those with ERBB2/HER2 mutation who may represent the first population to have a positive drug somatic mutation match. Similarly, those with ESR1 mutation may be the first to emerge for a negative association with the efficacy of aromatase-inhibitor treatment. One of the barriers to progress is the necessary focus on metastatic disease, which is often challenging, expensive, and risky to biopsy. In addition, because of the clonal heterogeneity of advanced disease, a single sample may not contain all the genomic information necessary for treatment. Thus, circulating tumor DNA analysis is perhaps one of the most practical and promising approaches. Conclusions and Relevance: Circulating tumor DNA analysis, once sensitive and broad enough, will accelerate progress in the quest to make NGS technologies relevant to breast cancer treatment. A broad and coordinated coalition to systematically connect somatic mutations to clinical and pharmacologic data will be critical for progress. We recommend instituting an open source encyclopedia, which would serve as a reference for NGS sequencing report interpretation and would be available to all clinicians to help direct therapy. PMID- 27560718 TI - Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse. AB - Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory thalamotectal pathway has not yet been characterized. The purpose of this study was to obtain a better understanding of the anatomical and neurochemical features of this pathway. Analysis of the distributions of retrogradely labeled cells after focal injections of retrograde tracer into the inferior colliculus (IC) of the mouse revealed that most of the subcortical descending projections originated in the brachium of the IC and the paralaminar portions of the auditory thalamus. In addition, the vast majority of thalamotectal cells were found to be negative for the calcium-binding proteins calbindin, parvalbumin, or calretinin. Using two different strains of GAD-GFP mice, as well as immunostaining for GABA, we found that a subset of neurons in the brachium of the IC is GABAergic, suggesting that part of this descending pathway is inhibitory. Finally, dual retrograde injections into the IC and amygdala plus corpus striatum as well into the IC and auditory cortex did not reveal any double labeling. These data suggest that the thalamocollicular pathway comprises a unique population of thalamic neurons that do not contain typical calcium-binding proteins and do not project to other paralaminar thalamic forebrain targets, and that a previously undescribed descending GABAergic pathway emanates from the brachium of the IC. J. Comp. Neurol. 525:885-900, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27560720 TI - Can States Simultaneously Improve Health Outcomes and Reduce Health Outcome Disparities? AB - INTRODUCTION: Reducing racial health disparities is often stated as a population health goal, but specific targets for such improvement are seldom set. It is often assumed that improving overall health outcomes will be linked to disparity reduction, but this is not necessarily the case. METHODS: We compared the annual change from 1999 through 2013 in combined-race (black and white) mortality with the annual change in absolute and relative racial mortality disparities for US states. RESULTS: Median annual improvement in combined-race mortality was 1.08% per year. Annual overall mortality rate reductions ranged from 0.24% per year in Oklahoma to 1.83% per year in Maryland. For disparities, the median for the black white absolute gap was 3.60% per year, and the median for the relative black-to white ratio was 1.19% per year. There was no significant correlation between the combined-race measure and either the absolute (0.03) or relative disparity measure reductions (-0.17). CONCLUSION: For mortality in US states over a recent period, improvement in the population mean and disparity reduction do not usually occur together. The disparity reduction rates observed may provide realistic guidance for public and private policy makers in setting goals for reducing population health disparity and creating investment priorities. As a starting point for discussion, the observed national median annual percentage improvement of 1.1 per year combined, 3.6% per year absolute gap reduction, and 1.2% per year relative gap reduction would be modest and reasonable goals. PMID- 27560721 TI - The Precarious Health of Young Mexican American Men in South Texas, Cameron County Hispanic Cohort, 2004-2015. AB - INTRODUCTION: Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US-Mexico border in South Texas and elucidate indications of chronic disease in young men. METHODS: We sampled all male participants from the Cameron County Hispanic Cohort, an ongoing population based cohort of Mexican Americans in Brownsville, Texas. We calculated descriptive statistics and stratified the sample into 3 age groups to estimate the prevalence of sociodemographic, behavioral, and clinical factors by age group and evaluated differences between age groups. RESULTS: Obesity prevalence was approximately 50% across all age groups (P = .83). Diabetes prevalence was high overall (26.8%), and 16.9% (95% confidence interval [CI], 10.1%-23.8%) of men younger than 35 had diabetes. More than 70% of these young men had elevated liver enzymes, and mean values of aspartate aminotransferase were significantly higher in younger men (45.0 u/L; 95% CI, 39.5-50.6 u/L) than in both older age groups. Less than 20% of young men had any form of health insurance. Current smoking was higher in young men than in men in the other groups, and the rate was higher than the national prevalence of current smoking among Hispanic men. CONCLUSIONS: We suggest a need for obesity and diabetes prevention programs and smoking cessation programs for men in this region. Opportunities exist to expand current intervention programs and tailor them to better reach this vulnerable population of young Hispanic men. Elevated liver enzymes in men younger than 35 suggest a substantial burden of liver abnormalities, a finding that warrants further study. PMID- 27560722 TI - The "Retrofitting" Approach to Adapting Evidence-Based Interventions: A Case Study of Pediatric Asthma Care Coordination, United States, 2010-2014. AB - Adaptation of evidence-based interventions upon implementation into new practice settings is universal, yet poorly understood. During a cross-site evaluation of the implementation of a proven intervention for pediatric asthma care coordination into 4 resource-challenged settings, we conducted in-depth interviews with site representatives, who reported how and why they modified intervention components. Interview notes were coded for themes. We focused on a single theme from a respondent who described the adaptation process as "backing" the intervention into ongoing services; we found evidence of a similar process at other sites. We labeled this process "retrofitting" to signify adaptation that consists of altering existing services to align with intervention components, rather than modifying the intervention to fit a new setting. Advantages of retrofitting may include allowing organizations to keep what works, capitalizing on existing support for program activities, elevating the role of local knowledge, and potentially promoting the sustainability of effective innovations. PMID- 27560723 TI - Differences in Fruit and Vegetable Intake by Race/Ethnicity and by Hispanic Origin and Nativity Among Women in the Special Supplemental Nutrition Program for Women, Infants, and Children, 2015. AB - INTRODUCTION: The objective of this exploratory study was to determine whether fruit and vegetable consumption differed by race/ethnicity, by origin and nativity among Hispanics, and by language preference (as an indicator of acculturation) among foreign-born Hispanics. METHODS: We recruited 723 women enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) and orally administered a questionnaire containing demographic items, validated measures of food security status and social desirability trait, and the Behavioral Risk Factor Surveillance System fruit and vegetable module. Differences in intakes of 100% fruit juice, fruit, cooked or canned beans, and dark green, orange-colored, and other vegetables were assessed by using analysis of covariance with Bonferroni post hoc tests. Analyses were controlled for age, pregnancy status, breastfeeding status, food security status, educational attainment, and social desirability trait. RESULTS: The frequency of vegetable intake differed by race/ethnicity (cooked or canned beans were consumed more often among Hispanic than non-Hispanic black and non-Hispanic white or other participants, orange-colored vegetables were consumed more often among Hispanics than non-Hispanic black participants, and other vegetables were consumed more often among non-Hispanic white or other than among non-Hispanic black and Hispanic participants), origin (other vegetables were consumed more often among Columbian and other Hispanics than Dominican participants) and nativity (orange colored vegetables were consumed more often among foreign-born than US-born Hispanics). Fruit and vegetable intake did not differ by language preference among foreign-born Hispanics. CONCLUSION: Differences in fruit and vegetable consumption among WIC participants by race/ethnicity and by Hispanic origin and nativity may have implications for WIC nutrition policies and nutrition education efforts. PMID- 27560724 TI - "You have the right to protect your health": Perceptions of Secondhand Smoke and Exposure Mitigation Strategies in Low-Income Patients With Heart Disease, San Francisco, 2011-2012. AB - We examined the understanding of the harms of secondhand smoke (SHS) exposure among low-income, hospitalized adults with cardiovascular disease. Participants were 15 nonsmokers reporting daily SHS exposure and 15 light or nondaily cigarette smokers. We coded responses from audiotaped semistructured interviews for themes. No participant spontaneously identified heart risks related to SHS exposure. Strategies to avoid SHS included verbal requests to not smoke and physically avoiding smoke; both smokers and nonsmokers prioritized politeness over urgency. Most participants thought a blood test quantifying SHS exposure would be clinically useful. Health education, assertiveness communication training, and protective policies (eg, smoke-free multiunit housing) also were supported. PMID- 27560767 TI - Direct Observation of the Formation Pathway of [Mo132] Keplerates. AB - The formation pathway of a closed spherical cluster [Mo132], starting from a library of building blocks of molybdate anions, has been reported. Electrospray ionization mass spectrometry, Raman spectroscopy, and theoretical studies describe the formation of such a complex cluster from a reduced and acidified aqueous solution of molybdate. Understanding the emergence of such an enormous spherical model cluster may lead to the design of new clusters in the future. Formation of such a highly symmetric cluster is principally controlled by charge balance and the emergence of more symmetric structures at the expense of less symmetric ones. PMID- 27560768 TI - Materialism across the life span: An age-period-cohort analysis. AB - This research examined the development of materialism across the life span. Two initial studies revealed that (a) lay beliefs were that materialism declines with age and (b) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has considered age only as a linear control variable, thereby precluding the possibility of more intricate relationships between age and materialism. Moreover, prior studies have relied on cross-sectional data and thus confound age and cohort effects. To improve on this, the main study used longitudinal data from 8 waves spanning 9 years of over 4,200 individuals (16 to 90 years) to examine age effects on materialism while controlling for cohort and period effects. Using a multivariate multilevel latent growth model, it found that materialism followed a curvilinear trajectory across the life span, with the lowest levels at middle age and higher levels before and after that. Thus, in contrast to lay beliefs, materialism increased in older age. Moreover, age effects on materialism differed markedly between 3 core themes of materialism: acquisition centrality, possession-defined success, and acquisition as the pursuit of happiness. In particular, acquisition centrality and possession-defined success were higher at younger and older age. Independent of these age effects, older birth cohorts were oriented more toward possession-defined success, whereas younger birth cohorts were oriented more toward acquisition centrality. The economic downturn since 2008 led to a decrease in acquisition as the pursuit of happiness and in desires for personal growth, but to an increase in desires for achievement. (PsycINFO Database Record PMID- 27560769 TI - Insulin degludec/insulin aspart vs biphasic insulin aspart 30 twice daily in Japanese patients with type 2 diabetes: A randomized controlled trial. AB - AIMS/INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a soluble combination of insulin degludec (70%) and insulin aspart (30%). The present exploratory trial investigated the safety of switching unit-to-unit from twice daily basal or pre-mix insulin to twice-daily IDegAsp in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: In this 6-week, open-label, parallel group, controlled trial, 66 participants were randomized (1:1) to receive either IDegAsp or biphasic insulin aspart 30 (BIAsp 30) twice daily at the same total daily dose as pre-trial insulin. During the trial, insulin doses were adjusted according to a pre-specified algorithm to achieve pre-breakfast and pre-dinner plasma glucose of 4.4-7.2 mmol/L. RESULTS: No severe hypoglycemic episodes occurred. There were no statistically significant differences in rates of confirmed hypoglycemia (rate ratio IDegAsp/BIAsp 30: 0.63, 95% confidence interval: 0.31-1.30) and confirmed nocturnal hypoglycemia (rate ratio: 0.49, 95% confidence interval: 0.10-2.38) for IDegAsp vs BIAsp 30. The hypoglycemia rate for IDegAsp was constant over the 6 weeks of treatment. IDegAsp and BIAsp 30 were both safe and well tolerated. Reduction in fasting plasma glucose was statistically significantly greater for IDegAsp than for BIAsp 30 (estimated treatment difference, IDegAsp-BIAsp 30: -1.6 mmol/L, 95% confidence interval: 2.4 to -0.8). The apparent decrease in mean postprandial plasma glucose increment (IDegAsp: 4.2-3.8 mmol/L; BIAsp 30: 4.5-2.8 mmol/L) was not statistically significantly different between treatments (estimated treatment difference: 1.0 mmol/L, 95% confidence interval: -0.1 to 2.2). CONCLUSIONS: Switching unit-to unit from basal or pre-mix insulin to IDegAsp seems not to be associated with any concerns related to hypoglycemia or general safety in Japanese patients with type 2 diabetes. PMID- 27560770 TI - The Role of Contextual Factors in Racial/Ethnic Disparities in Eye Care Use. PMID- 27560772 TI - Fate of thianthrene in biological systems. AB - 1. Thianthrene is a sulfur-containing tricyclic molecule distributed widely within the macrostructure of hydrocarbon fossil fuels. Identified nearly 150 years ago, its chemistry has been widely explored leading to insights into reaction mechanisms and radical ion formation. 2. It has been claimed to have therapeutic application in the treatment of dermal infections and to interfere with enzyme and nucleic acid function, but appears to have little toxicity. 3. Following its oral administration to the rat, the majority remained within the gastrointestinal tract. After three days, about 88% was detected in the combined excreta with the remainder still within the animal. It is readily taken up into fish from the surrounding aqueous environment and has been placed within the "bioaccumulative category" to be regarded with concern. 4. Mammalian metabolism appeared to be restricted to ring carbon oxidation and subsequent glucuronic acid conjugation. Small amounts of sulfoxide and disulfoxide were also formed. No ring degradation was evident. Microorganisms similarly undertook aromatic ring hydroxylation but were able also to rupture the ring system by attacking the carbon-sulfur linkages and thereby degrading the molecule. PMID- 27560771 TI - Inhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells. AB - Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor-suppressing. Thus we studied MDA-MB-231 and SK-BR-3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI-triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria. This inhibition increased mitochondrial cytochrome C release which augmented epirubicin-induced caspase dependent apoptosis and cytotoxicity. In addition, the lysosomal neutralizing agent ammonia chloride (AC), and Atg7 knockdown by siRNA, could inhibit epirubicin-triggered autophagy, enhance cytotoxicity, and increase caspase-9- and caspase-3-dependent apoptosis. Thus, autophagy plays a prosurvival role in EPI treated MDA-MB-231 and SK-BR-3 cells, and autophagy inhibition can potentially reverse this effect and increase the cytotoxicity of EPI. PMID- 27560773 TI - Inhibition of glutamate receptors reduces the homocysteine-induced whole blood platelet aggregation but does not affect superoxide anion generation or platelet membrane fluidization. AB - Homocysteine (Hcy) is an excitotoxic amino acid. It is potentially possible to prevent Hcy-induced toxicity, including haemostatic impairments, by antagonizing glutaminergic receptors. Using impedance aggregometry with arachidonate and collagen as platelet agonists, we tested whether the blockade of platelet NMDA (N methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors with their inhibitors: MK-801 (dizocilpine hydrogen maleate, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10 imine), CNQX (7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile) and UBP 302 (2-{[3-[(2S)-2-amino-2-carboxyethyl]-2,6-dioxo-3,6-dihydropyrimidin 1(2H) yl]methyl}benzoic acid) may hamper Hcy-dependent platelet aggregation. All the tested compounds significantly inhibited Hcy-augmented aggregation of blood platelets stimulated either with arachidonate or collagen. Hcy stimulated the generation of superoxide anion in whole blood samples in a concentration dependent manner; however, this process appeared as independent on ionotropic glutamate receptors, as well as on NADPH oxidase and protein kinase C, and was not apparently associated with the extent of either arachidonate- or collagen dependent platelet aggregation. Moreover, Hcy acted as a significant fluidizer of surface (more hydrophilic) and inner (more hydrophobic) regions of platelet membrane lipid bilayer, when used at the concentration range from 10 to 50 umol/l. However, this effect was independent on the Hcy action through glutamate ionotropic receptors, since there was no effects of MK-801, CNQX or UBP-302 on Hcy-mediated membrane fluidization. In conclusion, Hcy-induced changes in whole blood platelet aggregation are mediated through the ionotopic excitotoxic receptors, although the detailed mechanisms underlying such interactions remain to be elucidated. PMID- 27560774 TI - Dysprosium-carboxylate nanomeshes with tunable cavity size and assembly motif through ionic interactions. AB - We report the design of dysprosium directed metallo-supramolecular architectures on a pristine Cu(111) surface. By an appropriate selection of the ditopic molecular linkers equipped with terminal carboxylic groups (TPA, PDA and TDA species), we create reticular and mononuclear metal-organic nanomeshes of tunable internodal distance, which are stabilized by eight-fold DyO interactions. A thermal annealing treatment for the reticular Dy:TDA architecture gives rise to an unprecedented quasi-hexagonal nanostructure based on dinuclear Dy clusters, exhibiting a unique six-fold DyO bonding motif. All metallo-supramolecular architectures are stable at room temperature. Our results open new avenues for the engineering of supramolecular architectures on surfaces incorporating f-block elements forming thermally robust nanoarchitectures through ionic bonds. PMID- 27560775 TI - Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths - 27 States, 2013-2014. AB - In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50-100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid-involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states(?) with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013-2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in synthetic opioid deaths among high-burden states disproportionately involved persons aged 15-44 years and males, a pattern consistent with previously documented IMF-involved deaths (5). These findings, combined with the approximate doubling in fentanyl submissions during 2014-2015 (from 5,343 to 13,882) (6), underscore the urgent need for a collaborative public health and law enforcement response. PMID- 27560776 TI - A Triad of Highly Reduced, Linear Iron Nitrosyl Complexes: {FeNO}(8-10). AB - Given the importance of Fe-NO complexes in both human biology and the global nitrogen cycle, there has been interest in understanding their diverse electronic structures. Herein a redox series of isolable iron nitrosyl complexes stabilized by a tris(phosphine)borane (TPB) ligand is described. These structurally characterized iron nitrosyl complexes reside in the following highly reduced Enemark-Feltham numbers: {FeNO}(8) , {FeNO}(9) , and {FeNO}(10) . These {FeNO}(8 10) compounds are each low-spin, and feature linear yet strongly activated nitric oxide ligands. Use of Mossbauer, EPR, NMR, UV/Vis, and IR spectroscopy, in conjunction with DFT calculations, provides insight into the electronic structures of this uncommon redox series of iron nitrosyl complexes. In particular, the data collectively suggest that {TPBFeNO}(8-10) are all remarkably covalent. This covalency is likely responsible for the stability of this system across three highly reduced redox states that correlate with unusually high Enemark-Feltham numbers. PMID- 27560777 TI - Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses. AB - Active data screening is an integral part of many scientific activities, and mobile technologies have greatly facilitated this process by minimizing the reliance on large hardware instrumentation. In order to meet with the increasingly growing field of metabolomics and heavy workload of data processing, we designed the first remote metabolomic data screening platform for mobile devices. Two mobile applications (apps), XCMS Mobile and METLIN Mobile, facilitate access to XCMS and METLIN, which are the most important components in the computer-based XCMS Online platforms. These mobile apps allow for the visualization and analysis of metabolic data throughout the entire analytical process. Specifically, XCMS Mobile and METLIN Mobile provide the capabilities for remote monitoring of data processing, real time notifications for the data processing, visualization and interactive analysis of processed data (e.g., cloud plots, principle component analysis, box-plots, extracted ion chromatograms, and hierarchical cluster analysis), and database searching for metabolite identification. These apps, available on Apple iOS and Google Android operating systems, allow for the migration of metabolomic research onto mobile devices for better accessibility beyond direct instrument operation. The utility of XCMS Mobile and METLIN Mobile functionalities was developed and is demonstrated here through the metabolomic LC-MS analyses of stem cells, colon cancer, aging, and bacterial metabolism. PMID- 27560778 TI - High-Aspect-Ratio Ridge Structures Induced by Plastic Deformation as a Novel Microfabrication Technique. AB - Wrinkles on thin film/elastomer bilayer systems provide functional surfaces. The aspect ratio of these wrinkles is critical to their functionality. Much effort has been dedicated to creating high-aspect-ratio structures on the surface of bilayer systems. A highly prestretched elastomer attached to a thin film has recently been shown to form a high-aspect-ratio structure, called a ridge structure, due to a large strain induced in the elastomer. However, the prestretch requirements of the elastomer during thin film attachment are not compatible with conventional thin film deposition methods, such as spin coating, dip coating, and chemical vapor deposition (CVD). Thus, the fabrication method is complex, and ridge structure formation is limited to planar surfaces. This paper presents a new and simple method for constructing ridge structures on a nonplanar surface using a plastic thin film/elastomer bilayer system. A plastic thin film is attached to a stress-free elastomer, and the resulting bilayer system is highly stretched one- or two-dimensionally. Upon the release of the stretch load, the deformation of the elastomer is reversible, while the plastically deformed thin film stays elongated. The combination of the length mismatch and the large strain induced in the elastomer generates ridge structures. The morphology of the plastic thin film/elastomer bilayer system is experimentally studied by varying the physical parameters, and the functionality and the applicability to a nonplanar surface are demonstrated. Finally, we simulate the effect of plasticity on morphology. This study presents a new technique for generating microscale high aspect-ratio structures and its potential for functional surfaces. PMID- 27560779 TI - T regulatory lymphocytes in type 1 diabetes: Impaired CD25 expression and IL-2 induced STAT5 phosphorylation in pediatric patients. AB - T regulatory cells (Tregs) are essential for maintaining tolerance and preventing autoimmune diseases, such as type 1 diabetes (T1D). In our study, we investigated CD25 + FoxP3 + Tregs and thymic FoxP3 + Helios + Tregs in large cohorts of children with T1D at onset and with long-term T1D, and further in their relatives and healthy controls. We observed significantly decreased numbers of CD25 + FoxP3 + Tregs, but not FoxP3 + Helios + Tregs, in long-term patients compared with the control group and T1D onset. Furthermore, long-term T1D patients exhibited highly significant decrease of CD25 expression on both CD25 + FoxP3 + Tregs and FoxP3 + Helios + Tregs, independently on age or the duration of diabetes. A similar reduction of CD25 expression was also found in T1D relatives, more significant in those with positive autoantibodies. Low CD25 expression was associated with impaired signal transducer and activator of transcription 5 (STAT5) phosphorylation after IL-2 exposure. Our results show that the frequency of Tregs is altered in a large cohort of long-term T1D patients, a profound decrease in CD25 expression and altered IL-2 signaling are typical features of Tregs populations in long-term diabetic patients and their relatives. PMID- 27560780 TI - Survival and Participation in a Cancer Clinical Trial: A Provocative Relationship. PMID- 27560781 TI - Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy. AB - Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well as tubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR. PMID- 27560784 TI - Apoferritin nanocage as drug reservoir: is it a reliable drug delivery system? PMID- 27560782 TI - Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections. AB - The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6-12 months old) and children (1-14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = -0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naive B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue. PMID- 27560786 TI - Welcome message. PMID- 27560791 TI - Xenon Difluoride Mediated Fluorodecarboxylations for the Syntheses of Di- and Trifluoromethoxyarenes. AB - XeF2 is demonstrated to be a more proficient fluorine-transfer reagent than either NFSI or Selectfluor in fluorodecarboxylations of both mono- and difluoroaryloxy acetic acid derivatives. This method efficiently converts a wide range of neutral and electron-poor substrates to afford the desired di- and trifluoromethyl aryl ethers in good to excellent yields. The purifications are facile, and the reaction times are less than 5 min, which makes these fluorodecarboxylations promising for future PET-imaging applications. PMID- 27560792 TI - The intensity and correlates of the feelings of loneliness in people with psychosis. AB - OBJECTIVE: Loneliness is an established risk factor for numerous negative health outcomes. The aims of the present study were to compare the levels of loneliness between patients with psychotic disorders and members of the general population and to identify factors independently associated with loneliness in psychosis. METHODS: A total of 207 patients with psychotic disorders recruited between February 2013 and February 2015 from inpatient and day wards and an outpatient clinic of the Institute of Psychiatry and Neurology (IPN) in Warsaw (Poland) were included in this cross-sectional study. They were administered the De Jong Gierveld Loneliness Scale (DJGLS) and a set of instruments assessing three types of explanatory variables: socio-demographic, psychosocial and psychiatric (clinical). The comparison group was a random sample of 20,000 inhabitants of Poland who took part in the Generations and Gender Survey (GGS-PL) conducted in 2011. The two groups were matched for socio-demographic characteristics. RESULTS: The patient sample proved to be significantly lonelier than the general population sample. The higher level of loneliness in people with psychotic disorders was most strongly related to psychosocial factors, particularly more severe internalized stigma and lesser social support, followed by worse interpersonal competence and smaller social network. After adjusting for socio demographic and psychosocial variables, the only clinical variable significantly associated with more intense feelings of loneliness turned out to be the greater number of psychiatric inpatient admissions. The findings did not lend support to the view that socio-demographics play a major role in explaining variation in loneliness in psychosis. CONCLUSIONS: People with psychotic disorders are predisposed to experiencing elevated levels of loneliness. To counteract the pernicious effects of this on their health and well-being, there is a need for comprehensive therapeutic programs targeting self-stigma, enhancing social support networks and improving social skills. PMID- 27560793 TI - The intercell dynamics of T cells and dendritic cells in a lymph node-on-a-chip flow device. AB - T cells play a central role in immunity towards cancer and infectious diseases. T cell responses are initiated in the T cell zone of the lymph node (LN), where resident antigen-bearing dendritic cells (DCs) prime and activate antigen specific T cells passing by. In the present study, we investigated the T cell : DC interaction in a microfluidic device to understand the intercellular dynamics and physiological conditions in the LN. We show random migration of antigen specific T cells onto the antigen-presenting DC monolayer independent of the flow direction with a mean T cell : DC dwell time of 12.8 min and a mean velocity of 6 MUm min(-1). Furthermore, we investigated the antigen specific vs. unspecific attachment and detachment of CD8(+) and CD4(+) T cells to DCs under varying shear stress. In our system, CD4(+) T cells showed long stable contacts with APCs, whereas CD8(+) T cells presented transient interactions with DCs. By varying the shear stress from 0.01 to 100 Dyn cm(-2), it was also evident that there was a much stronger attachment of antigen-specific than unspecific T cells to stationary DCs up to 1-12 Dyn cm(-2). The mechanical force of the cell : cell interaction associated with the pMHC-TCR match under controlled tangential shear force was estimated to be in the range of 0.25-4.8 nN. Finally, upon performing attachment & detachment tests, there was a steady accumulation of antigen specific CD8(+) T cells and CD4(+) T cells on DCs at low shear stresses, which were released at a stress of 12 Dyn cm(-2). This microphysiological model provides new possibilities to recreate a controlled mechanical force threshold of pMHC-TCR binding, allowing the investigation of intercellular signalling of immune synapses and therapeutic targets for immunotherapy. PMID- 27560794 TI - Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors. AB - OBJECTIVES: Identifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment. METHODS: Twenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted "detected <12IU/ml" or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR. RESULTS: According to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively. CONCLUSION: HCV RNA "not detected" by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI) based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens. PMID- 27560795 TI - Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells. AB - OBJECTIVE: The aim of the present investigation was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoding glucocorticoid receptor (NR3C1) and some related proteins (SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, NNT) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of the glioma growth. METHODS: The expression of NR3C1,SGK1,SGK3, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by quantitative polymerase chain reaction. RESULTS: Inhibition of IRE1 signaling enzyme function up regulates the expression of NR3C1, SGK1, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells in comparison with the control glioma cells, with more significant changes for NR3C1, SGK1, and NNT genes. At the same time, the expression of SGK3 gene is strongly down-regulated in glioma cells upon inhibition of IRE1. We have also shown that hypoxia increases the expression of NR3C1, SGK1, NCOA2, ARHGAP35, and NNT genes but decreases SGK3 and NCOA1 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in U87 glioma cells enhances the eff ect of hypoxia on the expression of SGK1, SGK3, and NNT genes, but decreases the sensitivity of NR3C1 gene to hypoxic condition. Furthermore, the expression of NCOA1 gene is resistant to hypoxia in control glioma cells, but NCOA2 and ARHGAP35 genes are resistant to this condition in glioma cells without functional activity of IRE1 signaling enzyme. CONCLUSIONS: Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NR3C1, SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells in gene specific manner and that all these genes are regulated by hypoxia preferentially through IRE1 signaling pathway of the endoplasmic reticulum stress. PMID- 27560796 TI - Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats. AB - OBJECTIVE: Continuous exposure to cold leads to an activation of adaptive thermogenesis in the brown adipose tissue and induction of brown/beige cell phenotype in the white adipose tissue. Thermogenic response is associated with alternatively activated macrophages producing catecholamines, which subsequently activate the uncoupling protein 1 (UCP-1). The aim of this work was to elucidate the effect of cold exposure on catecholamine and immune responses associated with adipocyte browning in the mesenteric adipose tissue (mWAT) of rat. METHODS: The rats were exposed to continuous cold (4 degrees C) for 1 or 7 days. Catecholamines production and gene expressions of inflammatory and other factors, related to adipocyte "browning", were analyzed in the homogenized mWAT samples using 2-CAT ELISA kits. RESULTS: Cold exposure induced a sympathetic response in the mWAT, evidenced by the tyrosine hydroxylase (TH) protein level rise. Induction of non-sympathetical catecholamine production was observed 7 days after cold exposure by elevated TH and phenylethanolamine-N-methyltransferase (PNMT) expression, leading to an increased epinephrine levels. Cold exposure for 7 days stimulated the infiltration of macrophages, evaluated by F4/80 and CD68 expressions, and expression of anti-inflammatory mediators, while pro inflammatory cytokines were inhibited. Anti- inflammatory response, accompanied by de novo catecholamine production and up-regulation of beta3-adrenergic receptors, led to the stimulation of UCP-1 and PGC1alpha expression, suggesting a cold-induced "browning" of the mWAT, mediated by alternatively activated macrophages. CONCLUSIONS: The present data indicate that prolonged cold exposure may induce anti-inflammatory response in mWAT associated with induction of UCP-1 expression. Although functional thermogenesis in the mWAT is most likely redundant, a highly efficient dissipation of energy by UCP1 may affect the energy homeostasis in this visceral fat. PMID- 27560797 TI - An unusual case in endocrinology practice: Suture granuloma. AB - OBJECTIVE: Suture granuloma, the rare complication of thyroidectomy, results from the use of nonabsorbable suture materials. Despite its typical ultrasound images and benign course, it carries utmost importance in the diff erential diagnosis of lymph nodes, recurrent nodules, and recurrence in the case of thyroid cancers. Subject and Results. Fifty four years old female patient, who underwent bilateral thyroidectomy in July 2010, was diagnosed with multinodular goiter and incidentally discovered micropapillary carcinoma (2 mm). Four years later, she was readmitted to hospital due to painless swelling in the right and left anterior neck region. Ultrasonography revealed nodules with irregular boundaries, containing micro- and macro-calcifications and hyperechoic lines in both sides of the thyroid bed and isthmus. Fine needle aspiration biopsy was performed in the right and left sided mass and the cytological examination was compatible with the diagnosis of the suture granuloma. CONCLUSIONS: Suture granuloma should be considered in the differential diagnosis of the local recurrence. PMID- 27560798 TI - Elevated neutrophil-lymphocyte ratio in patients with euthyroid chronic autoimmune thyreotidis. AB - OBJECTIVE: The neutrophil-lymphocyte ratio (NLR), determined from peripheral blood, is accepted as an available and practical indicator of the systemic inflammation. In this study, we aimed to determine whether the NLR was higher in euthyroid chronic autoimmune thyreotidis (CAT) patients compared to a healthy control group. METHODS: A total of 112 patients were enrolled in this study, including 59 patients with euthyroid CAT on any form of therapy and 53 healthy controls. Th e CAT patients were similar in age to the healthy control group (mean 33.9+/-12.8 years versus 30.2+/-12.4 years, p=0.10). Measurements were available for the white blood cells (WBC), neutrophils, lymphocytes, platelets, C reactive protein (CRP), thyroid peroxidase immune antibody (anti-TPO), and anti thyroglobulin immune antibody (anti-TG). The NLR and platelet-lymphocyte ratio (PLR) were calculated. Differences between the CAT and control groups were tested using the student's t-test and the correlations were determined using Pearson's correlation coefficients. RESULTS: There were no differences between the CAT and control groups for WBCs (7.9+/-0.3 and 7.4+/-0.2, respectively; p=0.1) or neutrophils (5.5+/-0.3 and 5.4+/-1.1; p=0.9), but lymphocytes were higher in the CAT group (3.1+/-0.5 vs. 2.04+/-0.1; p=0.05) as was the NLR (4.0+/-0.7 vs. 2.0+/ 0.1; p=0.01). Th e NLR was positively correlated with CRP (r=0.6, p<0.001), anti TPO (r=0.3, p<0.001), anti-TG (r=0.3, p=0.006), WBCs (r=0.4, p<0.001), and the PLR (r=0.73, p<0.001). The PLR was also higher in the CAT than the control group (p=0.02). CONCLUSIONS: In this study, we found that NLR values were higher in euthyroid CAT patients than in a healthy control group and that NLR correlated with autoantibodies used to diagnose the disease. PMID- 27560799 TI - The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals. AB - Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl) and triphenyltin chloride (TPTCl), are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction. PMID- 27560800 TI - Multiple functions and essential roles of nuclear receptor coactivators of bHLH PAS family. AB - Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numerous metabolic pathways, and can be misregulated in many types of cancers. Their enormous functional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and highlight some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways. PMID- 27560801 TI - Fe3O4@polydopamine Composite Theranostic Superparticles Employing Preassembled Fe3O4 Nanoparticles as the Core. AB - Iron oxide (Fe3O4), polydopamine (PDA), and in particular their composites are examples of the safest nanomaterials for developing multifunctional nanodevices to perform noninvasive tumor diagnosis and therapy. However, the structures and performances of Fe3O4-PDA nanocomposites should be further perfected to enhance the theranostic efficiency. In this work, we demonstrate the fabrication of PDA capped Fe3O4 (Fe3O4@PDA) superparticles (SPs) employing preassembled Fe3O4 nanoparticles (NPs) as the cores. Owing to the collective effect of preassembled Fe3O4 NPs, the superparamagnetism and photothermal performance of Fe3O4@PDA SPs are greatly enhanced, thus producing nanodevices with improved magnetic resonance imaging (MRI)-guided photothermal efficiency. Systematical studies reveal that the molar extinction coefficient of the as-assembled Fe3O4 SPs is 3 orders of magnitude higher than that of individual Fe3O4 NPs. Also due to the high aggregation degree of Fe3O4 NPs, the T2-weighted MRI contrast is greatly enhanced for the SPs with r2 relaxivity of 230.5 mM(-1) s(-1), which is ~2.5 times larger than that of individual Fe3O4 NPs. The photothermal stability, physiological stability, and biocompatibility, as well as the photothermal performance of Fe3O4 SPs, are further improved by enveloping with PDA shell. PMID- 27560802 TI - Potentially Avoidable Peripartum Hysterectomies in Denmark: A Population Based Clinical Audit. AB - OBJECTIVE: To audit the clinical management preceding peripartum hysterectomy and evaluate if peripartum hysterectomies are potentially avoidable and by which means. MATERIAL AND METHODS: We developed a structured audit form based on explicit criteria for the minimal mandatory management of the specific types of pregnancy and delivery complications leading to peripartum hysterectomy. We evaluated medical records of the 50 Danish women with peripartum hysterectomy identified in the Nordic Obstetric Surveillance Study 2009-2012 and made short narratives of all cases. RESULTS: The most frequent indication for hysterectomy was hemorrhage. The two main initial causes were abnormally invasive placenta (26%) and lacerations (26%). Primary atony was third and occurred in 20%. Before hysterectomy another 26% had secondary atony following complications such as lacerations, retained placental tissue or coagulation defects. Of the 50 cases, 24% were assessed to be avoidable and 30% potentially avoidable. Hysterectomy following primary and secondary atony was assessed to be avoidable in 4/10 and 4/13 cases, respectively. Early sufficient suturing of lacerations and uterine ruptures, as well as a more widespread use of intrauterine balloons alone or in combination with uterine compression sutures (the sandwich model), could presumably have prevented about one fourth of the peripartum hysterectomies. CONCLUSION: More than 50% of peripartum hysterectomies seem to be avoidable by simple measures. In order to minimize the number of unnecessary peripartum hysterectomies, obstetricians and anesthesiologists should investigate individual cases by structured clinical audit, and disseminate and discuss the results for educational purposes. An international collaboration is warranted to strengthen our recommendations and reveal if they are generally applicable. PMID- 27560804 TI - Erratum: A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held. PMID- 27560803 TI - Molecular Evolution and Genetic Variation of G2-Like Transcription Factor Genes in Maize. AB - The productivity of maize (Zea mays L.) depends on the development of chloroplasts, and G2-like transcription factors play a central role in regulating chloroplast development. In this study, we identified 59 G2-like genes in the B73 maize genome and systematically analyzed these genes at the molecular and evolutionary levels. Based on gene structure character, motif compositions and phylogenetic analysis, maize G2-like genes (ZmG1- ZmG59) were divided into seven groups (I-VII). By synteny analysis, 18 collinear gene pairs and strongly conserved microsyntny among regions hosting G2-like genes across maize and sorghum were found. Here, we showed that the vast majority of ZmG gene duplications resulted from whole genome duplication events rather than tandem duplications. After gene duplication events, some ZmG genes were silenced. The functions of G2-like genes were multifarious and most genes that are expressed in green tissues may relate to maize photosynthesis. The qRT-PCR showed that the expression of these genes was sensitive to low temperature and drought. Furthermore, we analyzed differences of ZmGs specific to cultivars in temperate and tropical regions at the population level. Interestingly, the single nucleotide polymorphism (SNP) analysis revealed that nucleotide polymorphism associated with different temperature zones. Above all, G2-like genes were highly conserved during evolution, but polymorphism could be caused due to a different geographical location. Moreover, G2-like genes might be related to cold and drought stresses. PMID- 27560806 TI - The effect of water on discharge product growth and chemistry in Li-O2 batteries. AB - Understanding what controls Li-O2 battery discharge product chemistry and morphology is key to enabling its practical deployment as a low-cost, high specific-energy energy conversion technology. Several studies have recently shown that the addition of substantial quantities (hundreds to thousands ppm) of water and weak acids to dimethoxyethane (DME)-based electrolytes can significantly increase Li-O2 battery discharge capacity, without substantially changing the discharge product chemistry, which remains Li2O2. The exact mechanisms behind these device-level improvements, however, are not yet understood. In this study, we show that the presence of water in a DME-based electrolyte decreases the rate of Li2O2 nucleation on the electrode surface during Li-O2 battery discharge, using potentiostatic electrochemical measurements, and direct, ex situ observations of Li2O2 particles. We also show that adding water to an acetonitrile (MeCN)-based electrolyte results in LiOH upon discharge, as opposed to only Li2O2. Using first principles calculations, we propose that this change in discharge product chemistry is attributable to increased proton availability, as shown by a lower pKa for water in MeCN than in DME. This study combines kinetic and morphological analyses with first principles calculations, and elucidates relationships among electrolyte composition, discharge product chemistry and growth mechanisms for the rational design of efficient metal-air batteries. PMID- 27560805 TI - aPPRove: An HMM-Based Method for Accurate Prediction of RNA-Pentatricopeptide Repeat Protein Binding Events. AB - Pentatricopeptide repeat containing proteins (PPRs) bind to RNA transcripts originating from mitochondria and plastids. There are two classes of PPR proteins. The [Formula: see text] class contains tandem [Formula: see text]-type motif sequences, and the [Formula: see text] class contains alternating [Formula: see text], [Formula: see text] and [Formula: see text] type sequences. In this paper, we describe a novel tool that predicts PPR-RNA interaction; specifically, our method, which we call aPPRove, determines where and how a [Formula: see text] class PPR protein will bind to RNA when given a PPR and one or more RNA transcripts by using a combinatorial binding code for site specificity proposed by Barkan et al. Our results demonstrate that aPPRove successfully locates how and where a PPR protein belonging to the [Formula: see text] class can bind to RNA. For each binding event it outputs the binding site, the amino-acid nucleotide interaction, and its statistical significance. Furthermore, we show that our method can be used to predict binding events for [Formula: see text] class proteins using a known edit site and the statistical significance of aligning the PPR protein to that site. In particular, we use our method to make a conjecture regarding an interaction between CLB19 and the second intronic region of ycf3. The aPPRove web server can be found at www.cs.colostate.edu/~approve. PMID- 27560807 TI - A Large-Scale Analysis of Impact Factor Biased Journal Self-Citations. AB - Based on three decades of citation data from across scientific fields of science, we study trends in impact factor biased self-citations of scholarly journals, using a purpose-built and easy to use citation based measure. Our measure is given by the ratio between i) the relative share of journal self-citations to papers published in the last two years, and ii) the relative share of journal self-citations to papers published in preceding years. A ratio higher than one suggests that a journal's impact factor is disproportionally affected (inflated) by self-citations. Using recently reported survey data, we show that there is a relation between high values of our proposed measure and coercive journal self citation malpractices. We use our measure to perform a large-scale analysis of impact factor biased journal self-citations. Our main empirical result is, that the share of journals for which our measure has a (very) high value has remained stable between the 1980s and the early 2000s, but has since risen strongly in all fields of science. This time span corresponds well with the growing obsession with the impact factor as a journal evaluation measure over the last decade. Taken together, this suggests a trend of increasingly pervasive journal self citation malpractices, with all due unwanted consequences such as inflated perceived importance of journals and biased journal rankings. PMID- 27560808 TI - High School Students Residing in Educational Public Institutions: Health-Risk Behaviors. AB - Although several health-risk behaviors of adolescents have been described in the literature, data of high school students who reside at educational institutions in developing countries are scarce. This study aimed to describe behaviors associated with health risks among high school students who reside at an educational public institution and to associate these variables with the length of stay at the institution. This cross-sectional study was conducted during the year 2015 and included 122 students aged 14-19 years at a federal educational institution in the Midwest of Brazil; students were divided into residents of <8 months and those of >20 months. Information concerning the family socioeconomic status and anthropometric, dietary and behavioral profiles was investigated. Despite being physically active, students exhibited risk-associated behaviors such as cigarette and alcohol use and risky sexual behaviors that were exacerbated by fragile socioeconomic conditions and distance from family. A longer time in residence at the institution was associated with an older age (p <= 0.001), adequate body mass index (BMI; p = 0.02), nutritional knowledge (p = 0.01), and less doses of alcohol consumption (p <= 0.01) compared with those with shorter times in residence. In conclusion, the students exhibited different health-risk behaviors, and a longer institutional residence time, compared with a shorter time, was found to associate with the reduction of health-risk behaviors. PMID- 27560809 TI - Correction: Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects. AB - [This corrects the article DOI: 10.1371/journal.pone.0158779.]. PMID- 27560810 TI - [Not Available]. PMID- 27560811 TI - [Not Available]. PMID- 27560812 TI - [Not Available]. PMID- 27560814 TI - [Not Available]. PMID- 27560813 TI - [Not Available]. PMID- 27560815 TI - [Not Available]. PMID- 27560816 TI - [Not Available]. PMID- 27560817 TI - [Not Available]. PMID- 27560818 TI - [Not Available]. PMID- 27560819 TI - [Not Available]. PMID- 27560820 TI - [Not Available]. PMID- 27560821 TI - [Not Available]. PMID- 27560822 TI - [Not Available]. PMID- 27560823 TI - [Not Available]. PMID- 27560824 TI - Health Behavior and Metabolic Risk Factors Associated with Normal Weight Obesity in Adolescents. AB - OBJECTIVE: To explore health behaviors and metabolic risk factors in normal weight obese (NWO) adolescents compared with normal weight lean (NWL) peers. DESIGN AND METHODS: A cross-sectional study of 18-year-old students (n = 182, 47% female) in the capital area of Iceland, with body mass index within normal range (BMI, 18.5-24.9 kg/m2). Body composition was estimated via dual energy X-ray absorptiometry, fitness was assessed with maximal oxygen uptake (VO2max) during treadmill test, dietary intake through 24-hour recall, questionnaires explained health behavior and fasting blood samples were taken. NWO was defined as normal BMI and body fat >17.6% in males and >31.6% in females. RESULTS: Among normal weight adolescents, 42% (n = 76) were defined as NWO, thereof 61% (n = 46) male participants. Fewer participants with NWO were physically active, ate breakfast on a regular basis, and consumed vegetables frequently compared with NWL. No difference was detected between the two groups in energy- and nutrient intake. The mean difference in aerobic fitness was 5.1 ml/kg/min between the groups in favor of the NWL group (p<0.001). NWO was positively associated with having one or more risk factors for metabolic syndrome (Odds Ratio OR = 2.2; 95% confidence interval CI: 1.2, 3.9) when adjusted for sex. High waist circumference was more prevalent among NWO than NWL, but only among girls (13% vs 4%, p = 0.019). CONCLUSIONS: High prevalence of NWO was observed in the study group. Promoting healthy lifestyle with regard to nutrition and physical activity in early life should be emphasized regardless of BMI. PMID- 27560825 TI - Discovering Protein Receptors for Signaling Nucleotides. PMID- 27560826 TI - Effects of Mulching and Nitrogen on Soil Nitrate-N Distribution, Leaching and Nitrogen Use Efficiency of Maize (Zea mays L.). AB - Mulching and nitrogen are critical drivers of crop production for smallholders of the Loess Plateau in China. The purpose of this study was to investigate the effect of mulching and nitrogen fertilizer on the soil water content, soil nitrate-N content and vertical distribution in maize root-zone. The experiment was conducted over two consecutive years and used randomly assigned field plots with three replicates. The six treatments consisted of no fertilizer without plastic film (CK), plastic film mulching with no basal fertilizer and no top dressing (MN0), basal fertilizer with no top dressing and no mulching (BN1), plastic film mulching and basal fertilizer with no top dressing (MN1), basal fertilizer and top dressing with no mulching (BN2) and plastic film mulching with basal fertilizer and top dressing (MN2). In the top soil layers, the soil water content was a little high in the plastic film mulching than that without mulching. The mean soil water content from 0 to 40 cm without mulching were 3.35% lower than those measured in the corresponding mulching treatments in 31 days after sowing in 2012. The mulching treatment increased the soil nitrate-N content was observed in the 0-40-cm soil layers. The results indicate that high contents of soil nitrate-N were mainly distributed at 0-20-cm at 31 days after sowing in 2012, and the soil nitrate-N concentration in the MN2 treatment was 1.58 times higher than that did not receive fertilizer. The MN2 treatment greatly increased the soil nitrate-N content in the upper layer of soil (0-40-cm), and the mean soil nitrate-N content was increased nearly 50 mg kg-1 at 105 days after sowing compared with CK treatment in 2012. The soil nitrate-N leaching amount in MN1 treatment was 28.61% and 39.14% lower than BN1 treatment, and the mulch effect attained to 42.55% and 65.27% in MN2 lower than BN2 in both years. The yield increased with an increase in the basal fertilizer, top dressing and plastic film mulching, and the grain yield increase ranged from 31.41% to 83.61% in two consecutive years. The MN1 and MN2 treatment is recommended because it increased the grain yield and improved the fertilizer use efficiency, compared with the no mulching treatment. PMID- 27560827 TI - Modelling the Impact of Cell-To-Cell Transmission in Hepatitis B Virus. AB - Cell-free virus is a well-recognized and efficient mechanism for the spread of hepatitis B virus (HBV) infection in the liver. Cell-to-cell transmission (CCT) can be a more efficient means of virus propagation. Despite experimental evidence implying CCT occurs in HBV, its relative impact is uncertain. We develop a 3-D agent-based model where each hepatocyte changes its viral state according to a dynamical process driven by cell-free virus infection, CCT and intracellular replication. We determine the relative importance of CCT in the development and resolution of acute HBV infection in the presence of cytolytic (CTL) and non-CTL mechanisms. T cell clearance number is defined as the minimum number of infected cells needed to be killed by each T cell at peak infection that results in infection clearance within 12 weeks with hepatocyte turnover (HT, number of equivalent livers) <=3. We find that CCT has very little impact on the establishment of infection as the mean cccDNA copies/cell remains between 15 to 20 at the peak of the infection regardless of CCT strength. In contrast, CCT inhibit immune-mediated clearance of acute HBV infection as higher CCT strength requires higher T cell clearance number and increases the probability of T cell exhaustion. An effective non-CTL inhibition can counter these negative effects of higher strengths of CCT by supporting rapid, efficient viral clearance and with little liver destruction. This is evident as the T cell clearance number drops by approximately 50% when non-CTL inhibition is increased from 10% to 80%. Higher CCT strength also increases the probability of the incidence of fulminant hepatitis with this phenomenon being unlikely to arise for no CCT. In conclusion, we report the possibility of CCT impacting HBV clearance and its contribution to fulminant hepatitis. PMID- 27560829 TI - The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells. AB - Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystatin ablated eosinophil influx, reducing both weight loss and neutrophil recruitment without impairing anti-viral immune responses. AvCystatin also protected mice from excessive inflammation following primary RSV infection, significantly reducing neutrophil influx and cytokine production in the airways. Interestingly, we found that AvCystatin induced an influx of CD4+ FoxP3+ interleukin-10-producing T cells in the airway and lungs, correlating with immunoprotection, and the corresponding cells could also be induced by adoptive transfer of AvCystatin-primed F4/80+ macrophages. Thus, AvCystatin ameliorates enhanced RSV pathology without increasing susceptibility to, or persistence of, viral infection and warrants further investigation as a possible therapy for virus-induced airway disease. PMID- 27560830 TI - Assessing the Impact of Atopic Dermatitis on the Patients' Parents with the Visual Instrument 'Caregiver-PRISM'. AB - BACKGROUND: There is a need to improve the quality of communication between clinicians and parents of young patients with atopic eczema (AE). OBJECTIVE: To create a tool to measure the suffering that caregivers experience in association with their child's AE (Caregiver Pictorial Representation of Illness and Self Measure, Caregiver-PRISM), assess the validity and reliability, and identify factors associated with caregiver suffering. METHODS: Caregiver-PRISM was administered to 45 parents of patients from an AE outpatient service (Padua, Italy). RESULTS: Caregiver-PRISM had a good test-retest reliability (r = 0.85; t7 = 4.13; p < 0.05), content validity and construct validity when used in parents of AE children. Parents with a less positive family affective climate, higher education, or with children following a diet experienced higher suffering associated with their child's AE, demonstrated by lower Caregiver-PRISM scores (p < 0.05). CONCLUSION: Our results support the use of Caregiver-PRISM in parents of AE patients to assess suffering associated with patients' illness. PMID- 27560828 TI - Regulation of Polycystin-1 Function by Calmodulin Binding. AB - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal cytoplasmic tail. Most proteins that interact with PC1 have been found to bind via the cytoplasmic tail. Here we report that the PC1 tail has homology to the regulatory domain of myosin heavy chain including a conserved calmodulin-binding motif. This motif binds to CaM in a calcium dependent manner. Disruption of the CaM-binding motif in PC1 does not affect PC2 binding, cilia targeting, or signaling via heterotrimeric G-proteins or STAT3. However, disruption of CaM binding inhibits the PC1/PC2 calcium channel activity and the flow-dependent calcium response in kidney epithelial cells. Furthermore, expression of CaM-binding mutant PC1 disrupts cellular energy metabolism. These results suggest that critical functions of PC1 are regulated by its ability to sense cytosolic calcium levels via binding to CaM. PMID- 27560831 TI - Parent Experience of Care and Decision Making for Children Who Snore. AB - Importance: Sleep-disordered breathing (SDB) is prevalent and has an impact on the physical and behavioral health of children. Adenotonsillectomy (AT), the primary treatment, is subject to unexplained variation in utilization, which may be reduced by improving physician-patient communication and decision quality for this elective procedure. Objective: To identify factors are associated with parental experience and decision making in pediatric SDB and AT surgery. Design, Setting, and Participants: In this qualitative study, parents of children with prior SDB evaluation participated in semistructured, audiorecorded interviews. Open-ended questions regarded experiences of having a child with SDB, communication with pediatric clinicians and surgeons, and experiences with AT surgery. Recordings were transcribed and analyzed for emergent themes using grounded theory methodology. Eleven parents of children ages 2 to 17 years who had previously been diagnosed or treated for SDB were identified via purposive sampling and interviewed between January and April 2015. Interviews were conducted at locations convenient for the participants and separate from the pediatric clinic. A goal of this study was to ascertain how parents perceived sharing decisions with their physicians. Main Outcomes and Measures: Themes of parental experiences and treatment decision-making processes with pediatric SDB. Results: Overarching themes were inclusive of (1) clinical factors of SDB and AT and (2) clinician interpersonal behaviors and communication. Parents described an urgency that led them to seek evaluation or treatment, including fear that the child would stop breathing, or behavioral and/or cognitive delays. Parents often viewed surgery as a "last resort" and had explored alternate therapies prior to seeing the surgeon. Nearly all parents feared anesthesia more than AT surgery itself. Parents described satisfaction when physicians provided them with options, engaged their child in conversation, depicted SDB visually, and were responsive or accessible to questions. Parents regarded a trusting relationship with their pediatrician, confidence in the surgeon, and inclusion in decision making as important. Conclusions and Relevance: While clinical factors were influential for decision making, interpersonal factors helped parents feel comfortable and influenced their overall experience. Shared decision making, in which parents receive evidence-based information allowing them to accurately perceive risks, benefits, and alternatives about SDB treatment in the setting of trusting clinician-family relationships, may reduce parental decision conflict and improve decision quality toward AT surgery. PMID- 27560832 TI - Histamine regulates murine primary dendritic cell functions. AB - OBJECTIVE AND DESIGN: The modulation of antigen uptake and activation of dendritic cells (DCs) by histamine may function as a regulator of inflammation. Therefore, we sought to determine the impact of histamine on antigen uptake by and activation of murine DCs. MATERIAL AND METHODS: DCs from spleen and lung were either identified by flow cytometry or were immunomagnetically enriched. Cells were stimulated with histamine, and the regulation of MHC-II and co-stimulatory molecule expression (CD80, CD86, and ICOS-L) and antigen uptake were quantified by flow cytometry. Individual contributions of the histamine receptor subtypes were determined by using the antagonists mepyramine (histamine H1-receptor: H1R), famotidine (H2R), and JNJ 7777120 (H4R). RESULTS: Histamine accelerated the uptake of soluble antigen via the H1R, H2R, and H4R in splenic DCs. Co stimulatory molecule expression was enhanced already by enrichment procedures, thus, the analyses were performed in unseparated cell populations. Histamine enhanced the expression of CD86 and ICOS-L while expression of CD80 was unaffected. Antagonism at H1R, H2R, and H4R and at H1R and H4R reduced the histamine-induced enhanced expression of CD86 and ICOS-L, respectively. CONCLUSIONS: Histamine contributes to the regulation of the immunological synapse by stimulation of antigen uptake and activation of DCs via H1R, H2R, and H4R. PMID- 27560833 TI - New Entries in the Lottery of Facial GWAS Discovery. PMID- 27560834 TI - Preoperative metabolic syndrome and prognosis after radical resection for colorectal cancer: The Fujian prospective investigation of cancer (FIESTA) study. AB - This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow-up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98-fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40-3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor-node-metastasis stage I/II (HR = 3.94, 95% CI: 2.65-5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54-11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85-5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53 4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II. PMID- 27560835 TI - An organizing model for recent cognitive science work on the self. AB - An organizing model of 'the self' emerges from applying various kinds of brain injury to recent cognitive science and philosophical work on 'the self'. This model unifies various contents and mechanisms central to current notions of the self. The article then highlights several criteria and aspects of this notion of self. Qualities of the right type and level of psychological significance delineate 'the self' as an organizing concept useful for recent philosophical work and cognitive science research. PMID- 27560836 TI - Eu-doped Si-SiO2 core-shell nanowires for Si-compatible red emission. AB - The indirect bandgap of single-crystalline silicon has so far precluded the full integration of silicon microelectronics with photonics-which is expected to allow the realization of low-cost, high-speed optical information processing and communication in the future. Here we report the growth of europium (Eu)-doped Si SiO2 core-shell nanowires by an oxide-assisted chemical vapor deposition method. The Eu concentration in these nanowires is effectively improved by intentionally increasing the thickness of SiO2 shells. As a result, a strong Si-compatible red emission from Eu(3+) ions was observed under laser illumination. The effect of Eu(3+) concentration on the emission efficiency was comprehensively studied, with the highest efficiency at Eu content about 0.8 at%. The relaxation mechanism of this concentration dependent luminescence was further explored through lifetime measurements. In light of the strong characteristic red emission and nanoscale footprint, these nanowires are promising Si-compatible light emission materials for future integrated nanophotonics. PMID- 27560837 TI - Evolutionary analysis of apolipoprotein E by Maximum Likelihood and complex network methods. AB - Apolipoprotein E (apo E) is a human glycoprotein with 299 amino acids, and it is a major component of very low density lipoproteins (VLDL) and a group of high density lipoproteins (HDL). Phylogenetic studies are important to clarify how various apo E proteins are related in groups of organisms and whether they evolved from a common ancestor. Here, we aimed at performing a phylogenetic study on apo E carrying organisms. We employed a classical and robust method, such as Maximum Likelihood (ML), and compared the results using a more recent approach based on complex networks. Thirty-two apo E amino acid sequences were downloaded from NCBI. A clear separation could be observed among three major groups: mammals, fish and amphibians. The results obtained from ML method, as well as from the constructed networks showed two different groups: one with mammals only (C1) and another with fish (C2), and a single node with the single sequence available for an amphibian. The accordance in results from the different methods shows that the complex networks approach is effective in phylogenetic studies. Furthermore, our results revealed the conservation of apo E among animal groups. PMID- 27560838 TI - The association of very low-density lipoprotein receptor (VLDLR) haplotypes with egg production indicates VLDLR is a candidate gene for modulating egg production. AB - The very low-density lipoprotein receptor (VLDLR) transports egg yolk precursors into oocytes. However, our knowledge of the distribution patterns of VLDLR variants among breeds and their relationship to egg production is still incomplete. In this study, eight single nucleotide polymorphisms (SNPs) that account for 87% of all VLDLR variants were genotyped in Nick Chick (NC, n=91), Lohmann Brown (LohB, n=50) and Lueyang (LY, n=381) chickens, the latter being an Chinese indigenous breed. Egg production by NC and LY chickens was recorded from 17 to 50 weeks. Only four similar haplotypes were found in NC and LohB, of which two accounted for 100% of all NC haplotypes and 92.5% of LohB haplotypes. In contrast, there was considerable haplotypic diversity in LY. Comparison of egg production in LY showed that hens with NC-like haplotypes had a significantly higher production (p < 0.05) than those without the haplotypes. However, VLDLR expression was not significantly different between the haplotypes. These findings indicate a divergence in the distribution of VLDLR haplotypes between selected and non-selected breeds and suggest that the near fixation of VLDLR variants in NC and LohB is compatible with signature of selection. These data also support VLDLR as a candidate gene for modulating egg production. PMID- 27560839 TI - Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children. AB - Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism. PMID- 27560840 TI - I can see it when I believe it - or at least define it. PMID- 27560841 TI - Drosophila mating, inside and out. PMID- 27560843 TI - Intermittent Androgen Deprivation: Primum Non Nocere-"First Do NO Harm". PMID- 27560844 TI - Prevalence of maternal chronic diseases during pregnancy - a nationwide population based study from 1989 to 2013. AB - INTRODUCTION: There is substantial evidence of a negative impact of maternal chronic disease during pregnancy on reproductive outcomes. Knowledge of the prevalence of chronic diseases during pregnancy is limited, but essential for a focused preventive effort regarding optimal disease control during pregnancy. We aimed to analyze the prevalence of chronic diseases during pregnancy. MATERIAL AND METHODS: This register-based cohort study included all women giving birth in Denmark between 1989 and 2013 based on data from Danish health registers. Maternal chronic diseases included 23 disease categories of both physical and mental health conditions recorded within a period of 10 years before childbirth. RESULTS: We included 1 362 200 childbirths during the study period. The overall prevalence of maternal chronic disease increased from 3.71% in 1989 to 15.76% in 2013. The most frequently registered chronic diseases were chronic lung diseases/asthma (1.73%), thyroid disorders (1.50%) and anxiety and personality disorders (1.33%). Taking increasing maternal age at birth into account, the relative risk for women to have a chronic disease from 2009 to 2013 was 4.14 (95% CI 4.05-4.22), compared with mothers giving birth from 1989 to 1993. CONCLUSIONS: We found an increasing prevalence of maternal chronic disease during pregnancy and more than a four-fold increased risk of maternal chronic disease during pregnancy for childbirths in the period 2009 through 2013, compared with 1989 through 1993. The main limitation of our study is related to a potentially greater awareness and hence more careful registration of maternal chronic disease over time and thereby an increased tendency to register diseases. PMID- 27560842 TI - Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self association, cluster formation, and elevated viscosity. AB - Concentration-dependent reversible self-association (RSA) of monoclonal antibodies (mAbs) poses a challenge to their pharmaceutical development as viable candidates for subcutaneous delivery. While the role of the antigen-binding fragment (Fab) in initiating RSA is well-established, little evidence supports the involvement of the crystallizable fragment (Fc). In this report, a variety of biophysical tools, including hydrogen exchange mass spectrometry, are used to elucidate the protein interface of such non-covalent protein-protein interactions. Using dynamic and static light scattering combined with viscosity measurements, we find that an IgG1 mAb (mAb-J) undergoes RSA primarily through electrostatic interactions and forms a monomer-dimer-tetramer equilibrium. We provide the first direct experimental mapping of the interface formed between the Fab and Fc domains of an antibody at high protein concentrations. Charge distribution heterogeneity between the positively charged interface spanning complementarity-determining regions CDR3H and CDR2L in the Fab and a negatively charged region in CH3/Fc domain mediates the RSA of mAb-J. When arginine and NaCl are added, they disrupt RSA of mAb-J and decrease the solution viscosity. Fab-Fc domain interactions between mAb monomers may promote the formation of large transient antibody complexes that ultimately cause increases in solution viscosity. Our findings illustrate how limited specific arrangements of amino acid residues can cause mAbs to undergo RSA at high protein concentrations and how conserved regions in the Fc portion of the antibody can also play an important role in initiating weak and transient protein-protein interactions. PMID- 27560845 TI - Perioperative blood transfusion and the clinical outcomes of patients undergoing cholangiocarcinoma surgery: a systematic review and meta-analysis. AB - Several studies have reported different results on the association between perioperative blood transfusion (PBT) and clinical outcomes for patients undergoing cholangiocarcinoma surgery. So far, no systematic review and meta analysis have focused on this inconsistent issue. Therefore, we carried out a systematic review and meta-analysis to evaluate the association between PBT and the clinical outcomes of cholangiocarcinoma surgery patients. EMBASE, PubMed, Web of Science, and the Cochrane Library were searched from their inception to 6 April 2016 to evaluate the relationship between PBT and clinical outcomes for patients undergoing cholangiocarcinoma surgery. The pooled hazard ratio (HR) with a 95% confidence interval (CI) was calculated using the Cochrane Collaboration's RevMan 5.3 software. A total of 10 studies (1719 patients) were included in the meta-analysis. Pooled analysis showed that PBT was associated with worse 5-year survival rate (HR=1.67, 95% CI=1.41-1.98, P<0.0001) and median overall survival (OS) (HR=1.45, 95% CI=1.14-1.83, P=0.002) in the patients who underwent cholangiocarcinoma surgery. Subgroup analysis showed that intraoperative blood transfusion was also associated with worse 5-year survival rate (HR=1.95, 95% CI=1.49-2.57, P<0.00001). Intraoperative blood transfusion is associated with poor OS for patients undergoing cholangiocarcinoma surgery because it will increase the risk of death. Postoperative blood transfusion may not be associated with OS. In addition, the relationship between PBT and the postoperative complication rate of cholangiocarcinoma surgery is still unclear. PMID- 27560846 TI - Review of 103 Cases of Laparoscopic Repeat Liver Resection for Recurrent Hepatocellular Carcinoma. AB - INTRODUCTION: Laparoscopic repeat liver resection (LRLR) has been shown in small retrospective studies to be a safe and effective treatment for recurrent hepatocellular carcinoma (rHCC) in selected patients. The aim of this study was to perform a systematic review of the current literature to determine the safety, feasibility, and oncologic integrity of LRLR for rHCC. METHODS: A computerized search of the PubMed database was performed for all English language studies evaluating LRLR for HCC from January 1, 2005 to March 31, 2016. RESULTS: Ten studies reporting on 103 patients were included in this review. 30/51 (58.5%) patients had liver cirrhosis. In 66/95 (69.5%) patients, the index surgery was an open resection and this was a major hepatectomy in 8/49 (16.3%) patients. In 17/72 (23.6%) patients, LRLR was performed for tumors in the posterosuperior segments and in 21/60 (35%) for ipsilateral HCC recurrence. The median tumor size of rHCC ranged from 17-40 mm and 8/69 (11.6%) LRLR were for multifocal rHCC. In 100/103 (97%) patients LRLR was attempted via pure laparoscopy and 2 (1.9%) required open conversion. Median operation time of LRLR ranged from 73-343 minutes and the median blood loss ranged from 50 to 297 mL. The reported postoperative morbidity was 24/97 (24.7%) and there was no postoperative mortality. The median postoperative length of stay ranged from 3.5 to 11 days. Three studies compared the outcomes of LRLR versus open resection for rHCC and all three demonstrated a significant decrease in blood loss in favor of LRLR. CONCLUSION: In highly selected patients; LRLR for rHCC is feasible and safe. LRLR can be performed for patients with previous open LR, previous major hepatectomy, two previous LR, multiple tumors, liver cirrhosis, ipsilateral HCC recurrence, and cancers located in the difficult posterosuperior segments. Comparative studies have demonstrated that LRLR is superior to open repeat liver resection in terms of perioperative outcomes such as decreased blood loss and length of stay. PMID- 27560847 TI - Atypical Presentation of Chorioretinal Folds-Related Maculopathy. AB - PURPOSE: Chorioretinal folds are undulations that anatomically include the inner choroid, Bruch's membrane, and the retinal pigment epithelium, and secondarily affect the overlying neurosensory retina. We analyzed clinical data and management of six patients diagnosed with chorioretinal folds-related maculopathy with atypical presentations. CASE REPORT: The mean age of the six patients (five women) was 77 years. Best-corrected visual acuity (BCVA) ranged between 20/200 and 20/80. None of the patients had history of hypertension, cardiovascular diseases, or autoimmune disease, and they were all diagnosed with idiopathic chorioretinal folds. Case 1, 2, and 3 received intravitreal antivascular endothelial growth factor (VEGF) therapy; case 4 received intravitreal anti-VEGF and photodynamic therapy; case 5 received only photodynamic therapy; and case 6 received intravitreal injections of sustained-release dexamethasone implant (Ozurdex). In case 1 and 2, the use of ranibizumab resulted in BCVA improvement and resolution of sub-/intraretinal exudation. In case 3, ranibizumab led to a mild reduction of the intraretinal exudation but no changes in BCVA. In case 4 and 5, six intravitreal injections of ranibizumab with two photodynamic therapies and three photodynamic therapies, respectively, led to a mild reduction of the sub-/intraretinal exudation but no changes in BCVA. In case 6, five intravitreal injections of Ozurdex in both eyes led to reduction of the subretinal or intraretinal fluid accumulation and BCVA improvement. DISCUSSION: Choroidal vessel dilation and hyperpermeability may be involved in atypical presentations of chorioretinal folds-related maculopathy characterized by sub-/intraretinal fluid accumulation. Dilated and hyperpermeable choroidal vessels may result in focal retinal pigment epithelium alterations that can progress to choroidal neovascularization or chronic central serous chorioretinopathy-like maculopathy with or without telangiectatic retinal capillaries. Intravitreal anti-VEGF administration seems effective to treat choroidal neovascularization in stage 3 chorioretinal folds-related maculopathy, both anti-VEGF and photodynamic therapy seem to have only limited efficacy on chronic central serous chorioretinopathy like maculopathy (and telangiectatic retinal capillaries), whereas intravitreal injection of Ozurdex seems efficacious to treat chronic central serous chorioretinopathy-like maculopathy. PMID- 27560848 TI - Inter-Display Reproducibility of Contrast Sensitivity Measurement with iPad. AB - PURPOSE: To evaluate the reliability of measuring CS with uncalibrated iPads. METHODS: Six random iPads with retina display were calibrated with a colorimeter and the correlation between Luminance (L) and pixel level (y) was computed according to an exponential function. The mean and confidence interval (+/-2SD) obtained from the six iPads were calculated and the bit-stealing technique was applied for expanding y from 256 to 2540 possible values. The L of the optotype was computed for the selected contrast values (logC) represented in log units, using 0.1 log and 0.05 log steps. At each particular y, the contrast was considered reliable when the mean L plus 2SD was less than half the difference of luminance between two consecutive levels of contrast. Differences between the iPads for the Experimental logC were evaluated with the Friedman test. RESULTS: Luminance properties vary between devices, which were reflected in the computed Experimental logC (p < 0.0005). The contrast was found to be reliable for 0.1 log steps in the range from 0 to -2.2 log. On the other hand, for steps of 0.05 log, the contrast was only reliable for values ranging from 0 to -1.7 log. DISCUSSION: Both luminance and contrast steps differed between iPads with the same retina display, making it necessary to calibrate each display to achieve accurate luminance and contrast steps of 0.05 log units or less. However, for screening purposes utilizing contrast steps of 0.1 log unit or greater for a validated psychophysical test, calibration is not required to achieve accurate results across the displays described herein. PMID- 27560849 TI - Central Retinal Vein Occlusion Associated with Ulcerative Colitis. AB - PURPOSE: To report a case of central retinal vein occlusion without macular edema associated with ulcerative colitis and its novel treatment with intravitreal dexamethasone. CASE REPORT: A 40-year-old man with ulcerative colitis presented with sudden visual disturbances. An initial fundus examination showed subtle yellow-to-white patches within the inner retina of the right eye superotemporal to the fovea. There were intraretinal hemorrhages and cotton-wool spots within the superior vascular arcade and nasal to the optic disc. Despite initiation of systemic corticosteroids, 2 weeks later there was an increase in retinal hemorrhages, formation of cotton wool spots, and development of optic disc swelling in the right eye. The patient was eventually diagnosed with nonischemic central retinal vein occlusion associated with ulcerative colitis. He received sustained-release intravitreal dexamethasone, which led to the resolution of retinal hemorrhage, optic disc swelling, and cotton-wool spots. Three months after the injection, retinal hemorrhages were not detectable. However, ocular coherence imaging showed marked thinning of the inner retina at the locations that were previously hyper-reflective. CONCLUSIONS: Central retinal vein occlusion is an uncommon ophthalmologic manifestation associated with ulcerative colitis. Injection of intravitreal dexamethasone could be a viable treatment option in these patients even without the presence of macular edema. PMID- 27560850 TI - Exophthalmos, Diplopia, and Bilateral Eyelid Edema: Symptoms of Ocular Mastocytosis. AB - PURPOSE: Mastocytosis is characterized by clonal mast cell proliferation with accumulation within various organs and uncontrolled activation with excessive mast cell mediator release. Ocular manifestations have rarely been published. We describe a 63-year-old man with bilateral exophthalmos that led to the diagnosis of systemic mastocytosis. CASE REPORT: A patient presented with bilateral eyelid edema with exophthalmos associated with binocular diplopia. Ophthalmologic examination showed bilateral axial, symmetrical, and painless exophthalmos with eyelid edema, and limitation in elevation of the right eye. Visual acuity was normal. Orbital magnetic resonance imaging showed increased volume of both the superior and medial recti muscles and right inferior oblique muscle, and histopathological examination of orbital fat and muscle biopsies revealed an infiltration by mast cells. Serum tryptase was elevated. The patient also complained of a long history of pruritis and diffuse skin erythema that could be elicited with just mild pressure (Darier's sign). A bone marrow biopsy confirmed the infiltration of abnormal mast cells with a D816V mutation in the KIT gene. Treatment with cladribine was initiated and resulted in resolution of both ocular and systemic signs and symptoms that persisted without relapse 18 months after discontinuation. Ocular mastocytosis is a rare condition, which was previously reported to involve the conjunctiva, cornea, uvea, eyelid, orbit, and choroid. Cases of ocular mastocytosis can be classified into two main groups: mast cells tumors (mastocytomas) and ocular manifestations associated with systemic mastocytosis. Histological examination of ocular samples is rarely performed, and there are no standard criteria for the diagnosis of ocular mastocytosis. Our case emphasizes cladribine could represent an alternative treatment. CONCLUSIONS: Our case is the first published case of exophthalmos and eyelid edema associated with systemic mastocytosis confirmed by pathologic examination of periocular biopsies that was treated effectively with cladribine. PMID- 27560851 TI - Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic Eyes. AB - PURPOSE: To quantify the optimum pupil diameters for presbyopic eyes when environmental light levels vary from high photopic to low mesopic. METHODS: We computed the white light visual Strehl ratio from the polychromatic optical transfer function (VSOTF). The impact on image quality of retinal illuminance and the accompanying changes in photon noise were reflected in changing neural contrast sensitivity. VSOTF was calculated for focused and -2D defocused images, over a wide range of photopic and mesopic target luminances, and for pupil diameters ranging from 1 to 7 mm. We compare these modeling data to logMAR visual acuity measured under the same conditions. RESULTS: Optimum pupil depends on the relative gain of optical factors (diffraction and aberrations) and neural thresholds (photon noise effect). When light levels are reduced from 1000 to 2 cd/m, the pupil size that optimizes VSOTF for a well-focused presbyopic eye model also maximizes visual acuity and it increases from 2.5 to 4 mm. A 1-mm-diameter pupil maximizes VSOTF at all light levels when -2D of defocus are included, but at 2 cd/m the optimum pupil diameter for acuity increases slightly to 1.4 mm. At 0.2 cd/m, the pupil size that optimizes VSOTF remains 4 and 1 mm for a focused and -2D defocused eye, respectively, but significantly larger pupils are needed for maximal visual acuity. Reducing pupils to 30% of their natural size is beneficial for distance and near image quality and visual acuity at all light levels, producing more gains for near than for distance. CONCLUSIONS: A fixed 2- to 3-mm small pupil or a 30% pupil miosis can both produce near visual acuity gains without significant losses to distance acuity or image quality, and therefore can be considered as optimal for a presbyope experiencing a wide range of light levels. PMID- 27560852 TI - "Just out of reach: On the reliability of the action-sentence compatibility effect": Correction to Papesh (2015). AB - Reports an error in "Just out of reach: On the reliability of the action-sentence compatibility effect" by Megan H. Papesh (Journal of Experimental Psychology: General, 2015[Dec], Vol 144[6], e116-e141). In the article, the Procedure did not directly state that response options were not visible on the computer screen during Experiments 7 and 8. The first sentence of the Procedure for Experiment 7 should read, "Participants completed a modified button-press version of the experiment described in Experiment 4; unlike Experiment 4, Experiment 7 included no visible on-screen elements apart from the to-be-judged sentences, which came from Glenberg and Kaschak (2002)." (The following abstract of the original article appeared in record 2015-53127-006.) The action-sentence compatibility effect (ACE; Glenberg & Kaschak, 2002), a hallmark finding in Embodied Cognition, implicates the motor system in language comprehension. In the ACE, people process sentences implying movement toward or away from themselves, responding with actions toward or away from their bodies. These processes interact, implying a linkage between linguistic and motor systems. From a theoretical perspective, the ACE has been extremely influential, being widely cited evidence in favor of embodied cognition. The present study began as an attempt to extend the ACE in a new direction, but eventually became a series of attempts to simply replicate the effect. Across 8 experiments, I tested whether the ACE extends to a novel mouse tracking method and/or is susceptible to higher-order cognitive influences. In 3 experiments, attempts were made to "disembody" the ACE by presenting participants' names on the computer screen (as in Markman & Brendl, 2005). In each experiment, the ACE could not be disembodied, because the ACE did not occur. In further experiments, the ACE was not observed in reading times, regardless of response mode (mouse movements vs. button-presses) or stimuli, including those from the original research. Similarly, no ACE was observed in physical movement times. Bayes Factor analyses of the current experiments, and the previous ACE literature, suggest that the evidence for the ACE is generally weak: Many studies considered as positive evidence actually support the null hypothesis, and very few published results offer strong evidence for the ACE. Implications for the embodiment hypothesis are discussed. PMID- 27560853 TI - Cumulative weighing of time in intertemporal tradeoffs. AB - We examine preferences for sequences of delayed monetary gains. In the experimental literature, two prominent models have been advanced as psychological descriptions of preferences for sequences. In one model, the instantaneous utilities of the outcomes in a sequence are discounted as a function of their delays, and assembled into a discounted utility of the sequence. In the other model, the accumulated utility of the outcomes in a sequence is considered along with utility or disutility from improvement in outcome utilities and utility or disutility from the spreading of outcome utilities. Drawing on three threads of evidence concerning preferences for sequences of monetary gains, we propose that the accumulated utility of the outcomes in a sequence is traded off against the duration of utility accumulation. In our first experiment, aggregate choice behavior provides qualitative support for the tradeoff model. In three subsequent experiments, one of which incentivized, disaggregate choice behavior provides quantitative support for the tradeoff model in Bayesian model contests. One thread of evidence motivating the tradeoff model is that, when, in the choice between two single dated outcomes, it is conveyed that receiving less sooner means receiving nothing later, preference for receiving more later increases, but when it is conveyed that receiving more later means receiving nothing sooner, preference is left unchanged. Our results show that this asymmetric hidden-zero effect is indeed driven by those supporting the tradeoff model. The tradeoff model also accommodates all remaining evidence on preferences for sequences of monetary gains. PMID- 27560854 TI - Separate but correlated: The latent structure of space and mathematics across development. AB - The relations among various spatial and mathematics skills were assessed in a cross-sectional study of 854 children from kindergarten, third, and sixth grades (i.e., 5 to 13 years of age). Children completed a battery of spatial mathematics tests and their scores were submitted to exploratory factor analyses both within and across domains. In the within domain analyses, all of the measures formed single factors at each age, suggesting consistent, unitary structures across this age range. Yet, as in previous work, the 2 domains were highly correlated, both in terms of overall composite score and pairwise comparisons of individual tasks. When both spatial and mathematics scores were submitted to the same factor analysis, the 2 domain specific factors again emerged, but there also were significant cross-domain factor loadings that varied with age. Multivariate regressions replicated the factor analysis and further revealed that mental rotation was the best predictor of mathematical performance in kindergarten, and visual-spatial working memory was the best predictor of mathematical performance in sixth grade. The mathematical tasks that predicted the most variance in spatial skill were place value (K, 3rd, 6th), word problems (3rd, 6th), calculation (K), fraction concepts (3rd), and algebra (6th). Thus, although spatial skill and mathematics each have strong internal structures, they also share significant overlap, and have particularly strong cross-domain relations for certain tasks. (PsycINFO Database Record PMID- 27560855 TI - Structure at every scale: A semantic network account of the similarities between unrelated concepts. AB - Similarity plays an important role in organizing the semantic system. However, given that similarity cannot be defined on purely logical grounds, it is important to understand how people perceive similarities between different entities. Despite this, the vast majority of studies focus on measuring similarity between very closely related items. When considering concepts that are very weakly related, little is known. In this article, we present 4 experiments showing that there are reliable and systematic patterns in how people evaluate the similarities between very dissimilar entities. We present a semantic network account of these similarities showing that a spreading activation mechanism defined over a word association network naturally makes correct predictions about weak similarities, whereas, though simpler, models based on direct neighbors between word pairs derived using the same network cannot. (PsycINFO Database Record PMID- 27560856 TI - Understanding the effect of social context on learning: A replication of Xu and Tenenbaum (2007b). AB - Does the source of a piece of data-the process by which it is sampled-influence the inferences that we draw from it? Xu and Tenenbaum (2007b) reported a large effect of sampling process on learning: When a category exemplar was presented by a knowledgeable teacher, learners generalized more narrowly than when it was presented from an unknowledgeable source. In 5 experiments, 4 online and 1 in person, we attempted to replicate this result. Aggregating across our studies, we replicated the original finding of sensitivity to the sampling process, but with a smaller effect size than the original. We discuss these findings in the context of concerns about replicability more generally, as well as the practical relevance of sampling effects in psychological experiments. (PsycINFO Database Record PMID- 27560857 TI - Chemical and Cellular Antioxidant Activities of Chicken Breast Muscle Subjected to Various Thermal Treatments Followed by Simulated Gastrointestinal Digestion. AB - The effect of thermal treatments on chemical and cellular antioxidant activities of chicken breasts subjected to in vitro gastrointestinal digestion was investigated. Breast of Korat crossbred chicken (KC) and commercial broiler (BR) were cooked under various conditions, namely heating at 70 degrees C for 30 min (H-0.5) and 24 h (H-24), autoclaving (AC) at 121 degrees C for 15 min (AC-15) and 60 min (AC-60). Protein digestibility decreased upon the extreme thermal treatment of AC-60. The H-0.5 improved metal chelating activity of KC digesta, FRAP, and anti-liposome oxidation of BR digesta. Digesta of BR/H-0.5 and KC/AC-15 at 50 MUg/mL exhibited the highest cytoprotective effect against tert-butyl hydroperoxide (TBHP)-induced oxidative damage of HepG2 cells. In addition, the KC/AC-15 digesta at a concentration as low as 12.5 MUg/mL inhibited intracellular TBHP-induced reactive oxyfen species (ROS) production (P < 0.05). Thus, the digesta of KC breasts subjected to AC-15 provides not only nutritional value but also antioxidant activity at the cellular level. PMID- 27560858 TI - A New 5(6->7)abeo-sterol from the twigs of Podocarpus fleuryi. AB - A new 5(6->7)abeo-sterol with rarely reported [6-5-6-5]-fused rings, 3beta,5beta,6-trihydroxyl-B-norsitostane (1), along with 10 known compounds were isolated from the twigs of Podocarpus fleuryi. Their structures were elucidated by means of extensive spectroscopic analysis. Compound 1 was assessed for their cytotoxicity against five human tumour cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result showed that it had no activity. PMID- 27560859 TI - Significance of endometrial cells in cervical cytology. AB - This study evaluated the clinical significance of endometrial cells in Papanicolaou test (Pap test). A retrospective study was performed from the cytological database of Seoul National University Hospital. The results of Pap tests of women aged 40 years or older between January 1998 and December 2007 were sorted. Medical records were reviewed to identify the presence of endometrial cells from cytology, and cytologic and histologic follow-ups were performed to determine the clinical significance of the lesions. Among 75,673 Pap cases, 832 cases presenting normal endometrial cells (nEMCs) were included in this study. Their follow-up data are as follows: 800 with nEMCs, 5 with atypical EMCs (aEMCs), and 27 with endometrial cancer cells (EMCCs) on cytologic and histologic follow-ups. Significant endometrial or cervical diseases were found in 0.5%, 40%, and 100% of the cases on the following-up the pathologic examination of the women with nEMCs, aEMCs, and EMCCs, respectively. Unlike aEMCs and EMCCs, nEMCs on Pap tests did not increase the risk of developing endometrial hyperplasia or endometrial cancer in women aged 40 years or older. There is no clinical benefit to perform routine endometrial work-up in women with nEMCs, as recommended in the 2001 Bethesda System. However, symptomatic women with nEMCs on Pap test should perform endometrial work-up regardless of menopausal status. PMID- 27560860 TI - Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma. AB - The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 1) has shown robust anticancer efficacy in preclinical and clinical studies, but its development was halted due to marked systemic toxicities. Herein we demonstrate that DON inhibits glutamine metabolism and provides antitumor efficacy in a murine model of glioblastoma, although toxicity was observed. To enhance DON's therapeutic index, we utilized a prodrug strategy to increase its brain delivery and limit systemic exposure. Unexpectedly, simple alkyl ester-based prodrugs were ineffective due to chemical instability cyclizing to form a unique diazo-imine. However, masking both DON's amine and carboxylate functionalities imparted sufficient chemical stability for biological testing. While these dual moiety prodrugs exhibited rapid metabolism in mouse plasma, several provided excellent stability in monkey and human plasma. The most stable compound (5c, methyl-POM-DON-isopropyl-ester) was evaluated in monkeys, where it achieved 10-fold enhanced cerebrospinal fluid to plasma ratio versus DON. This strategy may provide a path to DON utilization in glioblastoma multiforme patients. PMID- 27560909 TI - Lack of compliance with consensus recommendations on the diagnosis of eosinophilic esophagitis (EoE) in published prevalence studies. A clinical and systematic review. AB - OBJECTIVE: According to consensus recommendations, the presence of esophageal symptoms, >15 eosinophils/high-power field and unresponsiveness to proton pump inhibitors are required for a diagnosis of eosinophilic esophagitis (EoE). Nevertheless, inconsistency in using these guidelines has been reported in recent publications. The objective of this study was to assess compliance with EoE diagnostic guidelines in published studies on EoE prevalence and to evaluate other clinical and methodological parameters. METHODS: A systematic review was conducted in articles published between 2008 and 2015 on the prevalence of EoE in unselected adults. Studies using EoE diagnostic definitions were judged to be compliant if they included all three components of the definition, partially compliant if they included two and non-compliant if they included one or none. Esophageal biopsy protocol differences and descriptions of patients' characteristics were determined. RESULTS: Among the 20 studies included, eight were performed in a hospital setting and 12 in the general population. Only 40.0% of studies were compliant, 35.0% were partially compliant and 25.0% were non compliant with the EoE diagnostic definition guidelines. In 60.0% of the studies a proton pump inhibitor trial was not administered. Only 30.0% adhered to the recommendations in the esophageal biopsy protocol. A lack of description of the history of atopia and endoscopic characteristics was observed in many studies. CONCLUSIONS: Partial or non-compliance with the EoE diagnostic definition was observed in most of the published prevalence studies after the publication of the first consensus. The results of these studies might be interpreted taking into account this context. PMID- 27560910 TI - [Clinical experience with omalizumab in patients with severe asthma. Real-world data]. AB - BACKGROUND: Omalizumab is a monoclonal antibody that is prescribed in a stepwise addition regimen for the treatment of severe asthma. OBJECTIVE: To report the experience of patients with severe asthma who were given omalizumab in accordance with international guides, in a context of real-world data. METHODS: Open, analytical, cross-sectional, retrospective, observational clinical study with real-world data. GINA 2006 Asthma Control Scheme was used to evaluate patients, and a questionnaire was used to evaluate patient characteristics, effectiveness, safety, and tolerance to omalizumab. RESULTS: 48 patients were studied, 34 women and 14 men with an average age of 39 years. The average disease duration was 26 years. Average serum IgE was 522 IU. At the beginning of treatment, all patients had uncontrolled asthma; at the end, 69% asthma control was obtained, 19% was partially controlled and 12% unchanged. The changes were observed at seven months on average. CONCLUSION: Omalizumab is effective and safe for treating severe asthma when applied in accordance with international guidelines for the management of bronchial asthma. PMID- 27560911 TI - [Evaluation and characterization of 125 patients with a history of reaction to beta-lactams]. AB - BACKGROUND: Reactions to beta-lactams are frequent and it is difficult to establish the relationship between the drug and symptoms. OBJECTIVE: To describe the clinical characteristics and explore the immunological mechanisms of patients with suspected adverse reaction to beta-lactams. METHODS: Retrospective study of patients with a history of beta-lactam reaction and tests for reactions to drugs. RESULTS: Out of 125 patients, 71 were women (56.8%); 73 had a history of immediate reaction and 52 delayed reaction; 590 allergy tests were done: specific IgE measurement, skin prick, patch, and provocation tests. The drugs most often related were amoxycillin, in 62 patients (49.6%), crystalline penicillin in 17 (13.6%), benzathine penicillin in 15 (12%), and cefalexin in 13 (10.4%). The severity of the reaction was mild in the majority (82%). 7.7% had a history of anaphylaxis and 10.8% sought care for a positive penicillin skin test, without history of reaction. Only 6.7% resulted in a positive test. More than 62% began testing two years after the reaction for which they sought care. CONCLUSIONS: The clinical history is insufficient to determine allergy to beta-lactams. In our sample, few patients with a history of beta-lactam reaction had evidence of immune-mediated reactions. PMID- 27560912 TI - [HLA DRB1*, DQB1*, DPA1*, and DPB1* and their association with the pathogenesis of leukemia in the population of Venezuela]. AB - BACKGROUND: The HLA complex involved is a factor in the pathogenesis of leukemia. OBJECTIVES: The presence of class II HLA alleles DRB1 *, DQB1 *, DPA1 *, and DPB1 * was evaluated in 47 patients with acute lymphoblastic leukemia (ALL) and 48 with chronic myeloid leukemia (CML) for comparison with 48 healthy volunteers in Zulia, Venezuela, and to evaluate potential associations of HLA with leukemia. METHODS: Low- and high-resolution PCR-SSP was used for class II HLA regions DRB1 *, DQB1 *, DPA1 *, and DPB1 * following the instructions of KIT Olerup SSP Genovision. RESULTS: Alleles HLA-DRB1*14, especially DRB1*14:21, -DPA1*1:06, DPA1*01:03,-DPA1*02:01, and the haplotypes HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03 DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 were associated with CML (RR > 3); alleles HLA-DRB1*13, -DQB1*02, -DPA1*01:05, DPA1*01:09 and the haplotypes HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 were protective (RR < 1). Alleles HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 had a positive association with ALL. Alleles HLA-DPA1*01:09, DPA1*02:01, -DPB1*02:01, -DPB1*03:01 and the haplotypes HLA-DPA1*01:03 DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01 DPB1*04:02 were negatively associated. CONCLUSIONS: The other association patterns identified suggest marked differences in the pathogenesis of leukemia, which suggests possible deficiencies in antigen presentation for ALL or potential effects of molecular mimicry in CML. PMID- 27560914 TI - [Transcultural translation-adaptation to Spanish of the Infants' Dermatitis Quality of Life questionnaire for children under four years with atopic dermatitis]. AB - BACKGROUND: Atopic dermatitis is observed in up to 20% of children, hence the importance of tools to support its evaluation. OBJECTIVE: To determine the validity and reliability of the Spanish adaptation of the IDQOL questionnaire in patients <4 years of age with atopic dermatitis (AD). METHODS: Translation and back-translation of the questionnaire; a pilot test was done in 30 children with AD to arrive at a final version. Internal reliability (Cronbach's alpha) and correlation of IDQOL and SCORAD scores (Pearson correlation coefficient) were measured. RESULTS: 102 children aged between two and 48 months were included. The Pearson correlation coefficient (r) of IDQOL and SCORAD scores was 0.697 (p = 0.0001), indicating a high positive correlation. The correlation between the severity measured by the caregiver and the SCORAD score (r = 0.565, p = 0.0001) proved to be low positive. The internal consistency of IDQOL using Cronbach's alpha was 0.84, indicating good consistency of the instrument for assessing quality of life. CONCLUSION: The IDQOL questionnaire in Spanish is a valid measure of quality of life in patients < 4 years with AD and is useful in monitoring and in clinical trials. PMID- 27560913 TI - [Influence of serum levels of vitamin D on IgE response in schoolchildren with asthma in poor communities]. AB - BACKGROUND: Asthma is a common disease in the world and vitamin D (Vit-D) has been associated with the presence and severity of this disease. OBJECTIVE: To establish the association between levels of Vit-D and IgE response in schoolchildren with asthma living in four cities in Colombia. METHODS: Case control study in 1340 schoolchildren (687 asthmatic and 653 controls) from communities in extreme poverty in Barranquilla, Cartagena, Santa Marta, and Monteria. Serum concentrations of Vit-D, total IgE, and anti-Dermatophagoides farinae, Periplaneta americana, and Ascaris lumbricoides (AL) specific IgE were measured. RESULTS: Controls reported higher concentrations of Vit-D [61.9 +/- 28.4 ng/mL] than cases [53 +/- 23.3 ng / mL] (p < 0.05). Total IgE was higher in cases (p < 0.05). Only anti-AL IgE showed a clear difference: in controls, optical density was 0.27 +/- 0.25; in cases, 0.22 +/- 0.24 (p < 0.05). Vit-D showed differences between cases and controls in each population. CONCLUSIONS: An association could not be demonstrated between Vit-D deficiency and asthma, as total IgE was elevated in patients and controls. The results suggest that Vit-D influences the specif IgE response in poor asthmatic children in areas endemic for helminthiasis. PMID- 27560915 TI - [Neurological disorders and immunosuppression in kidney transplant patients. Preliminary study]. AB - BACKGROUND: Neurological disorders in kidney transplant patients may be related to several factors, including high toxicity to the use of immunosuppressive drugs. OBJECTIVE: To find out whether there was association between neurological complications and immunosuppression in a sample of patients who received renal transplantation. METHODS: Cross-sectional study in which 121 renal transplant patients participated, of which 22 (18%) had neurological disorders, chi-squared test was used to analyze the relation between neurological disorders and comorbidity such as diabetes mellitus and hypertension and time of immunosuppressant use. A significance level of p <0.05 was accepted for all determinations. RESULTS: Of the subjects studied, 13 were male (59%) and nine female (41%). The mean age of the patients included in the study was 33 +/- 12 years. 59% of neurological disorders occurred between six months and five years after patients had received the transplant. Neurological alterations found were: tremor (7.4%), dizziness (4.1%), peripheral neuropathy (3.3%), headache (2.4%), and decreased strength (0.8%). CONCLUSION: No statistically significant association was found between neurological disorders and immunosuppressant use, or between them and the duration of immunosuppression. PMID- 27560916 TI - [The allergic child at school. What do we need to know?]. AB - Allergy is a multisystem disease in children that often occurs with the coexistence of diverse clinical manifestations that cause great impact on quality of life and academic performance due to sleep disorders arising from the disease or treatment, and absenteeism that children may experience. Because of the time spent in school, there is a possibility that allergic reactions may occur first in these facilities, where a lack of staff knowledge has been found regarding how to proceed in allergy crisis situations. Cooperative action among health teams, community, parents, and school authorities is essential to ensure that the school can prevent, recognize, and ensure quick access to emergency services (if needed) and treatment protocols for allergic reactions, thus allowing allergic children to be better protected in the school environment, which should be considered an extension of the home environment and an important arm in proper management to control the disease. PMID- 27560917 TI - [Modulation of immune response by bacterial lipopolysaccharides]. AB - Lipopolysaccharide (LPS) is a molecule that is profusely found on the outer membrane of Gram-negative bacteria and is also a potent stimulator of the immune response. As the main molecule on the bacterial surface, is also the most biologically active. The immune response of the host is activated by the recognition of LPS through Toll-like receptor 4 (TLR4) and this receptor-ligand interaction is closely linked to LPS structure. Microorganisms have evolved systems to control the expression and structure of LPS, producing structural variants that are used for modulating the host immune responses during infection. Examples of this include Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis and Salmonella spp. High concentrations of LPS can cause fever, increased heart rate and lead to septic shock and death. However, at relatively low concentrations some LPS are highly active immunomodulators, which can induce non-specific resistance to invading microorganisms. The elucidation of the molecular and cellular mechanisms involved in the recognition of LPS and its structural variants has been fundamental to understand inflammation and is currently a pivotal field of research to understand the innate immune response, inflammation, the complex host-pathogen relationship and has important implications for the rational development of new immunomodulators and adjuvants. PMID- 27560918 TI - [The research protocol IV: study variables]. AB - The variables in a research study are all that is measured, the information collected, or the data that is collected in order to answer the research questions, which are specified in the objectives. Their selection is essential to the research protocol. This article aims to point out the elements to be considered in the section of the variables. To avoid ambiguity, it is necessary to select only those that will help achieve the study objectives. It should subsequently be defined how they will be measured to ensure that the findings can be replicated; it is therefore desirable to include conceptual and operational definitions. From the methodological point of view, the classification of variables helps us understand how the relationship between them is conceptualized. Depending on the study design, the independent, dependent, universal, and confounding variables should be noted. Another indispensable element for planning statistical analyses is the scale of variable measurement. Therefore, one must specify whether the variables correspond to one of the following four: qualitative nominal, qualitative ordinal, quantitative range, or quantitative ratio. Finally, we should detail the measurement units of each variable. PMID- 27560919 TI - [Use of intravenous immunoglobulin in pregnancy. Report of a patient with common variable immunodeficiency]. AB - BACKGROUND: Common variable immunodeficiency is the most commonly-diagnosed primary immunodeficiency in adults; it is characterized by recurrent sinopulmonary and gastrointestinal infections, and increased incidence of malignancy and autoimmune processes. Many patients begin to have clinical manifestations during reproductive age. CASE REPORT: A 34-year-old woman with 12 weeks of gestation who was diagnosed with common variable immunodeficiency after recurrent episodes of rhinosinusitis, pharyngoamygdalitis, and pneumonia. 0.6 g/kg of IVIG was prescribed every 21 days during the second trimester; the patient only presented one episode of pharyngoamygdalitis, with adequate response to treatment with antibiotics. During the third trimester the dose was adjusted to every 14 days. The patient ended the pregnancy at term without complications, with a child without defects and with proper weight and size. CONCLUSIONS: The administration of immunoglobulin is the main treatment to control common variable immunodeficiency. While the recommended starting dose is 400-800 mg/kg intravenously every 3 to 4 weeks, there is no consensus on the dose to be used in pregnant women. The recommendation is to perform serum level controls before infusion to determine and adjust it. PMID- 27560920 TI - [Cross-reactivity in allergic fungal sinusitis. Case report]. AB - BACKGROUND: The presence of allergic mucin in allergic fungal sinusitis (AFS) is a manifestation that identifies it as a hypersensitivity process. AFS has a phenomenon of cross-reactivity to IgE-bound proteins having at least two shared epitopes. CLINICAL REPORT: A 13-year-old male with nasal obstructive symptoms of three years of evolution. An obstructive mass was identified in the sinuses through physical examination and CT. In endoscopic surgery, the left nostril polyp was identified with the macroscopic appearance of allergic mucin; the polyp was resected. Final histopathological examination using periodic acid-Schiff and Grocott's methenamine silver staining indicated Aspergillus. Two weeks after surgery, percutaneous tests showed sensitization to Alternaria, Helminthosporium sativum, and Deramatophagoides farianae with negativity to Aspergillus fumigatus. CONCLUSIONS: The absence of significant titers of specific IgE antibodies to Aspergillus fumigatus was the evidence that the hypersensitivity response was triggered by a pathogen other than that isolated in histopathological study, which coupled with positive tests for other fungi may be explained by the cross reactivity phenomenon in a phenomenon of likely hypersensitivity. PMID- 27560921 TI - Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment. AB - Current strategies to target tumors with nanomedicines rely on passive delivery via the enhanced permeability and retention effect, leveraging the disorganized tumor microvasculature to promote macromolecule extravasation and the reduced lymphatic and venous drainage that favor retention. Nonetheless, FDA approvals and clinical use of nanomedicines have lagged, reflecting failure to display superiority over conventional formulations. Here, we have exploited image-guided X-irradiation to augment nanoparticle accumulation in tumors. A single 5 Gy dose of radiation, below that required to significantly delay tumor growth, can markedly enhance delivery of macromolecules and nanoparticles. The radiation effect was independent of endothelial cell integrity, suggesting a primary role for damage to microvascular pericytes and/or interstitial extracellular matrix. Significantly, radiation-guided delivery potentiated the therapeutic effects of PEGylated liposomal doxorubicin on experimental tumors. Applied to patients, these results suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity. PMID- 27560922 TI - Ambient Aqueous Synthesis of Ultrasmall PEGylated Cu2-x Se Nanoparticles as a Multifunctional Theranostic Agent for Multimodal Imaging Guided Photothermal Therapy of Cancer. AB - Ultrasmall PEGylated Cu2-x Se nanoparticles with strong near-infrared absorption have been prepared by an ambient aqueous method. The resultant water-soluble and biocompatible nanoparticles are demonstrated to be a novel nanotheranostic agent for effective deep-tissue photoacoustic imaging, computed tomography imaging, single-photon emission computed tomography imaging, and photothermal therapy of cancer. PMID- 27560923 TI - Statistical Errors Affecting Percentage Differences, 95% CIs, and P Values. PMID- 27560925 TI - Sorting of chromosomes on FACSAria(TM) SORP for the preparation of painting probes. AB - High purity chromosome sorting can be performed on instruments such as MoFlo MLS and BD influx, which are stream-in-air sorters equipped with water-cooled high power lasers. The FACSAria is a true fixed alignment, low laser powered instrument with a quartz flow cell gel-coupled to the collection optics. However, whether high purity mouse and human chromosomes can be obtained by sorting on the BD FACSAria(TM) Special Order Research Product (FACSAria SORP) remains to be determined. Here, we report that the high resolution flow karyotype of mouse lymphocytes and normal male human peripheral blood mononuclear cells (hPBMCs) can be obtained on the FACSAria SORP using laser power settings of 50 mW for 355 nm and 20 mW for 444 nm excitation. Furthermore, the use of Fluorescence in situ hybridization (FISH) confirmed that chromosome paints prepared from the sorted chromosomes demonstrated high purity and signal specificity. Notably, human chromosome 12 was separated from the chromosome 9-12 cluster in the flow karyotype, and its identity was confirmed using FISH in trisomy 12 human ES cell lines B2-C7 and B2-B8. In addition, multicolor FISH (mFISH) with human chromosome painting probes to 13,18, 21, and sex chromosomes X and Y showed high signal specificity in hPBMCs. Taken together, our findings demonstrated that high resolution flow karyotype can be obtained using FACSAria SORP. Moreover, a FISH analysis confirmed high purity of the sorted chromosomes. Additionally, in contrast to centromeric satellite probes, chromosome painting probes with high specificity are more suitable for detection of chromosome aberrations, such as deletions and translocations, in prenatal diagnosis. (c) 2016 International Society for Advancement of Cytometry. PMID- 27560924 TI - Expression of Cell-Surface Marker ABCB5 Causes Characteristic Modifications of Glucose, Amino Acid and Phospholipid Metabolism in the G3361 Melanoma-Initiating Cell Line. AB - We present a pilot study aimed at determining the effects of expression of ATP binding cassette member B5 (ABCB5), a previously described marker for melanoma initiating cells, on cellular metabolism. Metabolic profiles for two groups of human G3361 melanoma cells were compared, i.e. wildtype melanoma cells with intact ABCB5 expression (ABCB5-WT) and corresponding melanoma cell variants with inhibited ABCB5 expression, through shRNA-mediated gene knockdown (ABCB5-KD). A comprehensive metabolomic analysis was performed by using proton and phosphorus NMR spectroscopy of cell extracts to examine water-soluble metabolites and lipids. Parametric and non-parametric statistical analysis of absolute and relative metabolite levels yielded significant differences for compounds involved in glucose, amino acid and phospholipid (PL) metabolism. By contrast, energy metabolism was virtually unaffected by ABCB5 expression. The sum of water-soluble metabolites per total protein was 17% higher in ABCB5-WT vs. ABCB5-KD G3361 variants, but no difference was found for the sum of PLs. Enhanced abundance was particularly pronounced for lactate (+ 23%) and alanine (+ 26%), suggesting an increase in glycolysis and potentially glutaminolysis. Increases in PL degradation products, glycerophosphocholine and glycerophosphoethanolamine (+ 85 and 123%, respectively), and redistributions within the PL pool suggested enhanced membrane PL turnover as a consequence of ABCB5 expression. The possibility of glycolysis modulation by an ABCB5-dependent IL1beta-mediated mechanism was supported by functional studies employing monoclonal antibody (mAb) dependent ABCB5 protein inhibition in wildtype G3361 melanoma cells. Our metabolomic results suggest that the underlying biochemical pathways may offer targets for melanoma therapy, potentially in combination with other treatment forms. PMID- 27560926 TI - High-Mobility Group Box-1 Protein Mediates the Regulation of Signal Transducer and Activator of Transcription-3 in the Diabetic Retina and in Human Retinal Muller Cells. AB - PURPOSE: The expression of high-mobility group box-1 (HMGB1) and signal transducer and activator of transcription-3 (STAT-3) is upregulated in the diabetic retina. We hypothesized that the activation of STAT-3 is under the control of HMGB1. METHODS: Retinas from 1-month-old diabetic rats and from normal rats intravitreally injected with HMGB1 and human retinal Muller glial cells (MIO M1) stimulated with HMGB1 or high glucose were studied by Western blot analysis and immunofluorescence. We also studied the effect of the HMGB1 inhibitor glycyrrhizin (GA) on high-glucose-induced pSTAT-3 nuclear translocation and upregulation in Muller cells and on pSTAT-3 expression in the retinas of diabetic rats (n = 7-10 in each group). In addition, we studied the effect of STAT-3 inhibitor on the HMGB1-induced induction of vascular endothelial growth factor (VEGF) by Muller cells and human retinal microvascular endothelial cell (HRMEC) migration. RESULTS: Treatment of retinal Muller cells with recombinant HMGB1 induced nuclear translocation of pSTAT-3 but did not alter pSTAT-3 expression. High glucose induced a significant upregulation of HMGB1 and pSTAT-3 upregulation and nuclear translocation in retinal Muller cells. GA co-treatment normalized the high-glucose-induced upregulation of HMGB1 and pSTAT-3 upregulation and nuclear translocation in Muller cells. Intravitreal administration of HMGB1 in normal and diabetic rats upregulated pSTAT-3 expression in the retina. GA attenuated the diabetes-induced upregulation of pSTAT-3 in the retina. The STAT-3 inhibitor attenuated HMGB1-induced VEGF upregulation by Muller cells and HRMEC migration. CONCLUSIONS: The results suggest a role for HMGB1 in the modulation of STAT-3 expression in the diabetic retina. PMID- 27560927 TI - Novel NAD+-Farnesal Dehydrogenase from Polygonum minus Leaves. Purification and Characterization of Enzyme in Juvenile Hormone III Biosynthetic Pathway in Plant. AB - Juvenile Hormone III is of great concern due to negative effects on major developmental and reproductive maturation in insect pests. Thus, the elucidation of enzymes involved JH III biosynthetic pathway has become increasing important in recent years. One of the enzymes in the JH III biosynthetic pathway that remains to be isolated and characterized is farnesal dehydrogenase, an enzyme responsible to catalyze the oxidation of farnesal into farnesoic acid. A novel NAD+-farnesal dehydrogenase of Polygonum minus was purified (315-fold) to apparent homogeneity in five chromatographic steps. The purification procedures included Gigacap S-Toyopearl 650M, Gigacap Q-Toyopearl 650M, and AF-Blue Toyopearl 650ML, followed by TSK Gel G3000SW chromatographies. The enzyme, with isoelectric point of 6.6 is a monomeric enzyme with a molecular mass of 70 kDa. The enzyme was relatively active at 40 degrees C, but was rapidly inactivated above 45 degrees C. The optimal temperature and pH of the enzyme were found to be 35 degrees C and 9.5, respectively. The enzyme activity was inhibited by sulfhydryl agent, chelating agent, and metal ion. The enzyme was highly specific for farnesal and NAD+. Other terpene aldehydes such as trans- cinnamaldehyde, citral and alpha- methyl cinnamaldehyde were also oxidized but in lower activity. The Km values for farnesal, citral, trans- cinnamaldehyde, alpha- methyl cinnamaldehyde and NAD+ were 0.13, 0.69, 0.86, 1.28 and 0.31 mM, respectively. The putative P. minus farnesal dehydrogenase that's highly specific towards farnesal but not to aliphatic aldehydes substrates suggested that the enzyme is significantly different from other aldehyde dehydrogenases that have been reported. The MALDI-TOF/TOF-MS/MS spectrometry further identified two peptides that share similarity to those of previously reported aldehyde dehydrogenases. In conclusion, the P. minus farnesal dehydrogenase may represent a novel plant farnesal dehydrogenase that exhibits distinctive substrate specificity towards farnesal. Thus, it was suggested that this novel enzyme may be functioning specifically to oxidize farnesal in the later steps of JH III pathway. This report provides a basic understanding for recombinant production of this particular enzyme. Other strategies such as adding His-tag to the protein makes easy the purification of the protein which is completely different to the native protein. Complete sequence, structure and functional analysis of the enzyme will be important for developing insect-resistant crop plants by deployment of transgenic plant. PMID- 27560929 TI - Preface. PMID- 27560928 TI - Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition. AB - OBJECTIVES: Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and independent effects of rifaximin need to be elucidated in the setting of MHE associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin. METHODS: Four germ-free (GF) mice groups were used (1) GF, (2) GF+rifaximin, (3) Humanized with stools from an MHE patient, and (4) Humanized+rifaximin. Mice were followed for 30 days while rifaximin was administered in chow at 100 mg/kg from days 16-30. We tested for ammonia generation (small-intestinal glutaminase, serum ammonia, and cecal glutamine/amino-acid moieties), systemic inflammation (serum IL-1beta, IL-6), intestinal barrier (FITC-dextran, large-/small-intestinal expression of IL-1beta, IL-6, MCP-1, e-cadherin and zonulin) along with microbiota composition (colonic and fecal multi-tagged sequencing) and function (endotoxemia, fecal bile acid deconjugation and de-hydroxylation). RESULTS: All mice survived until day 30. In the GF setting, rifaximin decreased intestinal ammonia generation (lower serum ammonia, increased small-intestinal glutaminase, and cecal glutamine content) without changing inflammation or intestinal barrier function. Humanized microbiota increased systemic/intestinal inflammation and endotoxemia without hyperammonemia. Rifaximin therapy significantly ameliorated these inflammatory cytokines. Rifaximin also favorably impacted microbiota function (reduced endotoxin and decreased deconjugation and formation of potentially toxic secondary bile acids), but not microbial composition in humanized mice. CONCLUSIONS: Rifaximin beneficially alters intestinal ammonia generation by regulating intestinal glutaminase expression independent of gut microbiota. MHE associated fecal colonization results in intestinal and systemic inflammation in GF mice, which is also ameliorated with rifaximin. PMID- 27560930 TI - Sociodemographic associations of 4-year overweight and obese incidence among a racially diverse cohort of healthy weight 18-year-olds. AB - BACKGROUND: Emerging adulthood is a critical time for excess weight gain. Risk can be masked if recommended overweight and obesity cut-points for Asians are not employed. OBJECTIVES: To determine the associations among sociodemographic factors and occurrence of overweight and obesity among normal weight 18-year olds. METHODS: Normal weight (body mass index < 25 kg m-2 ; <23 kg m-2 for Asians) 18-year-old (9037 boys, 13 786 girls, 36% Hispanic, 34% non-Hispanic Whites, 10% Black, 5% Asian) members of a healthcare organization in 2008 were followed through 2012 to identify incidence of overweight and obesity. Hazard ratios (HR) and 95% confidence intervals (CI) were determined controlling for sex, race/ethnicity, neighbourhood education, neighbourhood income and smoking status. RESULTS: After 3 years of follow-up, the HR for overweight was 1.28 (95% CI: 1.12, 1.45) in the lowest quartile of neighbourhood education compared with the highest. Asians and Pacific Islanders had greater risk of overweight (HR 2.89, 95% CI: 2.55, 3.28; HR 3.13, 95% CI 2.23, 4.38) than non-Hispanic Whites. Girls and Blacks were more likely to become obese than boys and non-Hispanic Whites, as were those living in the lowest neighbourhood education quartile and lower neighbourhood income quartiles. CONCLUSIONS: Girls, Asians, Blacks and those living in low education and income neighbourhoods during adolescence are at risk for excessive weight gain trajectories. PMID- 27560931 TI - Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study. AB - AIMS: The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population based cohort study. MATERIAL AND METHODS: The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40-70 years, who participated from 2005-2008 (baseline) without metabolic syndrome and were followed up from 2008-2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. RESULTS: During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422-0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124-0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046-0.0143, P<0.001). CONCLUSIONS: The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID- 27560932 TI - An Enriched Environment Promotes Shelter-Seeking Behaviour and Survival of Hatchery-Produced Juvenile European Lobster (Homarus gammarus). AB - The high loss of newly released hatchery-reared European lobster (Homarus gammarus) juveniles for stock enhancement is believed to be the result of maladaptive anti-predator behaviour connected to deprived stimuli in the hatchery environment. Our objective was to learn if an enriched hatchery environment enhances shelter-seeking behaviour and survival. In the "naive" treatment, the juveniles were raised in single compartments without substrate and shelter whereas juveniles in the "exposed" treatment experienced substrate, shelter and interactions with conspecifics. Three experiments with increasing complexity were conducted. Few differences in shelter-seeking behaviour were found between treatments when one naive or one exposed juvenile were observed alone. When observing interactions between one naive and one exposed juvenile competing for shelter, naive juveniles more often initiated the first aggressive encounter. The third experiment was set up to simulate a release for stock enhancement. Naive and exposed juveniles were introduced to a semi-natural environment including substrate, a limited number of shelters and interactions with conspecifics. Shelter occupancy was recorded three times during a period of 35 days. Exposed juveniles occupied more shelters, grew larger and had higher survival compared with naive juveniles. Our results demonstrate that experience of environmental complexity and social interactions increase shelter-seeking ability and survival in hatchery reared lobster juveniles. PMID- 27560933 TI - The Role of 18F-FDG PET/CT Integrated Imaging in Distinguishing Malignant from Benign Pleural Effusion. AB - OBJECTIVE: The aim of our study was to evaluate the role of 18F-FDG PET/CT integrated imaging in differentiating malignant from benign pleural effusion. METHODS: A total of 176 patients with pleural effusion who underwent 18F-FDG PET/CT examination to differentiate malignancy from benignancy were retrospectively researched. The images of CT imaging, 18F-FDG PET imaging and 18F FDG PET/CT integrated imaging were visually analyzed. The suspected malignant effusion was characterized by the presence of nodular or irregular pleural thickening on CT imaging. Whereas on PET imaging, pleural 18F-FDG uptake higher than mediastinal activity was interpreted as malignant effusion. Images of 18F FDG PET/CT integrated imaging were interpreted by combining the morphologic feature of pleura on CT imaging with the degree and form of pleural 18F-FDG uptake on PET imaging. RESULTS: One hundred and eight patients had malignant effusion, including 86 with pleural metastasis and 22 with pleural mesothelioma, whereas 68 patients had benign effusion. The sensitivities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging in detecting malignant effusion were 75.0%, 91.7% and 93.5%, respectively, which were 69.8%, 91.9% and 93.0% in distinguishing metastatic effusion. The sensitivity of 18F-FDG PET/CT integrated imaging in detecting malignant effusion was higher than that of CT imaging (p = 0.000). For metastatic effusion, 18F-FDG PET imaging had higher sensitivity (p = 0.000) and better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with CT imaging (Kappa = 0.917 and Kappa = 0.295, respectively). The specificities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were 94.1%, 63.2% and 92.6% in detecting benign effusion. The specificities of CT imaging and 18F-FDG PET/CT integrated imaging were higher than that of 18F-FDG PET imaging (p = 0.000 and p = 0.000, respectively), and CT imaging had better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with 18F-FDG PET imaging (Kappa = 0.881 and Kappa = 0.240, respectively). CONCLUSION: 18F-FDG PET/CT integrated imaging is a more reliable modality in distinguishing malignant from benign pleural effusion than 18F-FDG PET imaging and CT imaging alone. For image interpretation of 18F-FDG PET/CT integrated imaging, the PET and CT portions play a major diagnostic role in identifying metastatic effusion and benign effusion, respectively. PMID- 27560935 TI - Chiral carbon dots derived from guanosine 5'-monophosphate form supramolecular hydrogels. AB - Guanosine 5'-monophosphate, (5'-GMP), is a self-assembling natural nucleotide that has unique potential to form ordered supramolecular structures. We herein describe an intriguing property of Na2(5'-GMP) to form blue emitting chiral carbon dots (G-dots) that exhibit excitation dependent down-conversion and up conversion fluorescence signature and self-assemble to form fluorescent hydrogels. PMID- 27560934 TI - A Proteomic Approach to Lipo-Chitooligosaccharide and Thuricin 17 Effects on Soybean GerminationUnstressed and Salt Stress. AB - Salt stress is an important abiotic stressor affecting crop growth and productivity. Of the 20 percent of the terrestrial earth's surface available as agricultural land, 50 percent is estimated by the United Nations Environment Program to be salinized to the level that crops growing on it will be salt stressed. Increased soil salinity has profound effects on seed germination and germinating seedlings as they are frequently confronted with much higher salinities than vigorously growing plants, because germination usually occurs in surface soils, the site of greatest soluble salt accumulation. The growth of soybean exposed to 40 mM NaCl is negatively affected, while an exposure to 80 mM NaCl is often lethal. When treated with the bacterial signal compounds lipo chitooligosaccharide (LCO) and thuricin 17 (Th17), soybean seeds (variety Absolute RR) responded positively at salt stress of up to 150 mM NaCl. Shotgun proteomics of unstressed and 100 mM NaCl stressed seeds (48 h) in combination with the LCO and Th17 revealed many known, predicted, hypothetical and unknown proteins. In all, carbon, nitrogen and energy metabolic pathways were affected under both unstressed and salt stressed conditions when treated with signals. PEP carboxylase, Rubisco oxygenase large subunit, pyruvate kinase, and isocitrate lyase were some of the noteworthy proteins enhanced by the signals, along with antioxidant glutathione-S-transferase and other stress related proteins. These findings suggest that the germinating seeds alter their proteome based on bacterial signals and on stress, the specificity of this response plays a crucial role in organ maturation and transition from one stage to another in the plants' life cycle; understanding this response is of fundamental importance in agriculture and, as a result, global food security. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with identifier PXD004106. PMID- 27560936 TI - Insufficient Evidence for Rare Activation of Latent HIV in the Absence of Reservoir-Reducing Interventions. PMID- 27560937 TI - The Role of High-Resolution Magic Angle Spinning 1H Nuclear Magnetic Resonance Spectroscopy for Predicting the Invasive Component in Patients with Ductal Carcinoma In Situ Diagnosed on Preoperative Biopsy. AB - The purpose of this study was to evaluate the role of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy in patients with ductal carcinoma in situ (DCIS) diagnosed on preoperative biopsy. We investigated whether the metabolic profiling of tissue samples using HR-MAS 1H NMR spectroscopy could be used to distinguish between DCIS lesions with or without an invasive component. Our institutional review board approved this combined retrospective and prospective study. Tissue samples were collected from 30 patients with pure DCIS and from 30 with DCIS accompanying invasive carcinoma. All patients were diagnosed with DCIS by preoperative core-needle biopsy and underwent surgical resection. The metabolic profiling of tissue samples was performed by HR-MAS 1H NMR spectroscopy. All observable metabolite signals were identified and quantified in all tissue samples. Metabolite intensity normalized by total spectral intensities was compared according to the tumor type using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). By univariate analysis, the metabolite concentrations of choline-containing compounds obtained with HR-MAS 1H NMR spectroscopy did not differ significantly between the pure DCIS and DCIS accompanying invasive carcinoma groups. However, the GPC/PC ratio was higher in the pure DCIS group than in the DCIS accompanying invasive carcinoma group (p = 0.004, Bonferroni-corrected p = 0.064), as well as the concentration of myo-inositol and succinate. By multivariate analysis, the OPLS DA models built with HR-MAS MR metabolic profiles could clearly discriminate between pure DCIS and DCIS accompanying invasive carcinoma. Our preliminary results suggest that HR-MAS MR metabolomics on breast tissue may be able to distinguish between DCIS lesions with or without an invasive component. PMID- 27560938 TI - Topology Universality and Dissimilarity in a Class of Scale-Free Networks. AB - We study the effect of subtle changes on the evolution in the scale-free (SF) networks. Three extended models are evolved based on competition and inner anti preferential deletion in growth and preferential attachment processes. By nonlinear and dynamic controlling on randomness and determinacy, three models can self-organize into scale-free networks, and diverse scaling exponents appear. Moreover, the model with more determinacy has more stringent parameter control than randomness, especially in the edge deletion. Our results suggest that the nature of the topology universality and dissimilarity in SF networks may be the subtle changes of randomness and determinacy. PMID- 27560939 TI - The success rate of TED upper eyelid retraction reoperations. AB - Although reoperation rates for upper lid retraction surgery for thyroid eye disease (TED) typically range between 8% and 23%, there is little literature describing the outcomes of these second operations. In this retrospective observational cohort study, all patients that underwent surgery for upper eyelid retraction over a 14-year period at a single institution were included. Cases were included if a second eyelid retraction surgery was performed during the study period. Success of surgery was defined as a marginal reflex distance (MRD1) of 2.5 to 4.5 mm in each eye and less than 1 mm difference in MRD1 between the eyes. Overcorrection and undercorrection were defined as above and below these bounds, respectively. 72 eyes in 49 patients were included in the study. The mean age was 56.6 (+/-11.5) years. By definition, all patients had at least 1 lid lengthening surgery for upper eyelid retraction, and at least 1 subsequent surgery. For this second surgery, 61 eyes (85%) underwent retraction surgery and 11 eyes (15%) underwent ptosis surgery. After this second operation, 31% were undercorrected and 33% were overcorrected. A third surgery was performed in 19 eyes (25%), 12 had surgery for residual retraction and 7 for ptosis. After the third operation 10% of eyes were under corrected and 11% were over corrected. Four patients underwent a fourth surgery: one for retraction and three for ptosis. Success was noted in 35% after the second surgery and 44% after the third. Surgical success in eyelid retraction surgery increases from a second to a third consecutive surgery, and residual asymmetry was roughly equally distributed between over- and undercorrection. PMID- 27560940 TI - Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach. AB - We report on the design of a polymeric prodrug of the anticancer agent paclitaxel (PTX) by a grafting-from-drug approach. A chain transfer agent for reversible addition fragmentation chain transfer (RAFT) polymerization was efficiently and regioselectively linked to the C2' position of paclitaxel, which is crucial for its bioactivity. Subsequent RAFT polymerization of a hydrophilic monomer yielded well-defined paclitaxel-polymer conjugates with high drug loading, water solubility, and stability. The versatility of this approach was further demonstrated by omega-end post-functionalization with a fluorescent tracer. In vitro experiments showed that these conjugates are readily taken up into endosomes where native PTX is efficiently cleaved off and then reaches its subcellular target. This was confirmed by the cytotoxicity profile of the conjugate, which matches those of commercial PTX formulations based on mere physical encapsulation. PMID- 27560941 TI - Correction: Slug Is Increased in Vascular Remodeling and Induces a Smooth Muscle Cell Proliferative Phenotype. AB - [This corrects the article DOI: 10.1371/journal.pone.0159460.]. PMID- 27560942 TI - Asthma and Rhinitis Are Associated with Less Objectively-Measured Moderate and Vigorous Physical Activity, but Similar Sport Participation, in Adolescent German Boys: GINIplus and LISAplus Cohorts. AB - INTRODUCTION: Physical activity (PA) protects against most noncommunicable diseases and has been associated with decreased risk of allergic phenotype, which is increasing worldwide. However, the association is not always present; furthermore it is not clear whether it is strongest for asthma, rhinitis, symptoms of these, or atopic sensitization; which sex is most affected; or whether it can be explained by either avoidance of sport or exacerbation of symptoms by exercise. Interventions are thus difficult to target. METHODS: PA was measured by one-week accelerometry in 1137 Germans (mean age 15.6 years, 47% boys) from the GINIplus and LISAplus birth cohorts, and modeled as a correlate of allergic symptoms, sensitization, or reported doctor-diagnosed asthma or rhinitis. RESULTS: 8.3% of children had asthma, of the remainder 7.9% had rhinitis, and of the remainder 32% were sensitized to aero-allergens (atopic). 52% were lung-healthy controls. Lung-healthy boys and girls averaged 46.4 min and 37.8 min moderate-to-vigorous PA per day, of which 14.6 and 11.4 min was vigorous. PA in allergic girls was not altered, but boys with asthma got 13% less moderate and 29% less vigorous PA, and those with rhinitis with 13% less moderate PA, than lung-healthy boys. Both sexes participated comparably in sport (70 to 84%). Adolescents with wheezing (up to 68%, in asthma) and/or nose/eye symptoms (up to 88%, in rhinitis) were no less active. CONCLUSIONS: We found that asthma and rhinitis, but not atopy, were independently associated with low PA in boys, but not in girls. These results indicate that allergic boys remain a high-risk group for physical inactivity even if they participate comparably in sport. Research into the link between PA and allergy should consider population-specific and sex-specific effects, and clinicians, parents, and designers of PA interventions should specifically address PA in allergic boys to ensure full participation. PMID- 27560943 TI - CD52-Negative NK Cells Are Abundant in the Liver and Less Susceptible to Alemtuzumab Treatment. AB - BACKGROUND: T-cell depleting strategies have become an integral part of immunosuppressive regimens in organ transplantation. Alemtuzumab is a humanized monoclonal antibody against CD52, a cell-surface antigen on several immune cells. It has been suggested that lymphocyte depletion increases the risk of serious infections. However, this has not been observed with short-term alemtuzumab treatment in an organ transplant setting. For induction therapy using alemtuzumab following liver transplantation, we found that T- and B-cell numbers declined rapidly after alemtuzumab therapy; however, the natural killer (NK) cell number was sustained. NK cells are important effectors of innate immunity. Since the effects of alemtuzumab on NK cell functions, especially those of liver NK cells, are unknown, this study aimed to investigate this in detail. METHODS: To assess the effect of alemtuzumab on NK cells, samples were obtained from 7 organ donors and examined by flow cytometry using Annexin V and propidium iodide. Phenotypical and functional differences within subsets of NK cells with different levels of CD52 expression were determined by flow cytometry and in vitro cytotoxicity assays. RESULTS: CD52 expression on NK cells was lower than that on other lymphocyte subsets. The liver contained a large number of CD52- NK cells compared with the peripheral blood. In vitro treatment of liver-derived NK cells with alemtuzumab did not result in cell death. In contrast, co-incubation with alemtuzumab induced cell death in peripheral blood mononuclear cells and non-NK cells in the liver. Furthermore, CD52- liver NK cells were more cytotoxic and produced more IFN-gamma than CD52+ NK cells after cytokine activation. CONCLUSION: The liver contains a large number of CD52- NK cells. These cells are refractory to alemtuzumab and have robust activity. These findings indicate that CD52- NK cells persist and could protect against infection after alemtuzumab based lymphocyte depletion. PMID- 27560944 TI - Regulation of Organic Hydroperoxide Stress Response by Two OhrR Homologs in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa ohrR and ospR are gene homologs encoding oxidant sensing transcription regulators. OspR is known to regulate gpx, encoding a glutathione peroxidase, while OhrR regulates the expression of ohr that encodes an organic peroxide specific peroxiredoxin. Here, we show that ospR mediated gpx expression, like ohrR and ohr, specifically responds to organic hydroperoxides as compared to hydrogen peroxide and superoxide anion. Furthermore, the regulation of these two systems is interconnected. OspR is able to functionally complement an ohrR mutant, i.e. it regulates ohr in an oxidant dependent manner. In an ohrR mutant, in which ohr is derepressed, the induction of gpx expression by organic hydroperoxide is reduced. Likewise, in an ospR mutant, where gpx expression is constitutively high, oxidant dependent induction of ohr expression is reduced. Moreover, in vitro binding assays show that OspR binds the ohr promoter, while OhrR binds the gpx promoter, albeit with lower affinity. The binding of OhrR to the gpx promoter may not be physiologically relevant; however, OspR is shown to mediate oxidant-inducible expression at both promoters. Interestingly, the mechanism of OspR-mediated, oxidant-dependent induction at the two promoters appears to be distinct. OspR required two conserved cysteines (C24 and C134) for oxidant-dependent induction of the gpx promoter, while only C24 is essential at the ohr promoter. Overall, this study illustrates possible connection between two regulatory switches in response to oxidative stress. PMID- 27560945 TI - A Novel Flexible Inertia Weight Particle Swarm Optimization Algorithm. AB - Particle swarm optimization (PSO) is an evolutionary computing method based on intelligent collective behavior of some animals. It is easy to implement and there are few parameters to adjust. The performance of PSO algorithm depends greatly on the appropriate parameter selection strategies for fine tuning its parameters. Inertia weight (IW) is one of PSO's parameters used to bring about a balance between the exploration and exploitation characteristics of PSO. This paper proposes a new nonlinear strategy for selecting inertia weight which is named Flexible Exponential Inertia Weight (FEIW) strategy because according to each problem we can construct an increasing or decreasing inertia weight strategy with suitable parameters selection. The efficacy and efficiency of PSO algorithm with FEIW strategy (FEPSO) is validated on a suite of benchmark problems with different dimensions. Also FEIW is compared with best time-varying, adaptive, constant and random inertia weights. Experimental results and statistical analysis prove that FEIW improves the search performance in terms of solution quality as well as convergence rate. PMID- 27560946 TI - Pharmacodynamic effects of a new fixed-dose clopidogrel-aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial. AB - Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG(r)). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 +/- 52 vs. 207 +/- 60 PRU; mean difference, -5 PRU; 90% confidence interval of difference, -23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). "BASE" and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values >=0.822) and TEG(r) measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel-aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin. PMID- 27560947 TI - Strong Genetic Differentiation of Submerged Plant Populations across Mountain Ranges: Evidence from Potamogeton pectinatus in Iran. AB - Biogeographic barriers for freshwater biota can be effective at various spatial scales. At the largest spatial scale, freshwater organisms can become genetically isolated by their high mountain ranges, vast deserts, and inability to cross oceans. Isolation by distance of aquatic plants is expected to be stronger across than alongside mountain ridges whereas the heterogeneity of habitats among populations and temporary droughts may influence connectivity and hamper dispersal. Suitable aquatic plant habitats became reduced, even for the widespread submerged Potamogeton pectinatus L. (also named Stuckenia pectinata) giving structure to various aquatic habitats. We compared the level of genetic diversity in a heterogeneous series of aquatic habitats across Iran and tested their differentiation over distances and across mountain ranges (Alborz and Zagros) and desert zones (Kavir), with values obtained from temperate region populations. The diversity of aquatic ecosystems across and along large geographic barriers provided a unique ecological situation within Iran. P. pectinatus were considered from thirty-six sites across Iran at direct flight distances ranging from 20 to 1,200 km. Nine microsatellite loci revealed a very high number of alleles over all sites. A PCoA, NJT clustering and STRUCTURE analysis revealed a separate grouping of individuals of southeastern Iranian sites and was confirmed by their different nuclear ITS and cpDNA haplotypes thereby indicating an evolutionary significant unit (ESU). At the level of populations, a positive correlation between allelic differentiation Dest with geographic distance was found. Individual-based STRUCTURE analysis over 36 sites showed 7 genetic clusters. FST and RST values for ten populations reached 0.343 and 0.521, respectively thereby indicating that allele length differences are more important and contain evolutionary information. Overall, higher levels of diversity and a stronger differentiation was revealed among Iranian P. pectinatus than previously observed for temperate European regions, due to regional differences across mountain ranges over long distances. PMID- 27560948 TI - Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015. AB - In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(?) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(S) and recent release from an institution such as a jail, rehabilitation facility, or hospital. PMID- 27560949 TI - Repeated Lumbar Punctures for Non-Clinical Indications: How Do Patients Feel? PMID- 27560951 TI - Human pluripotent stem cell-derived cardiomyocyte based models for cardiotoxicity and drug discovery. PMID- 27560952 TI - Affibody Scaffolds Improve Sesquiterpene Production in Saccharomyces cerevisiae. AB - Enzyme fusions have been widely used as a tool in metabolic engineering to increase pathway efficiency by reducing substrate loss and accumulation of toxic intermediates. Alternatively, enzymes can be colocalized through attachment to a synthetic scaffold via noncovalent interactions. Here we describe the use of affibodies for enzyme tagging and scaffolding. The scaffolding is based on the recognition of affibodies to their anti-idiotypic partners in vivo, and was first employed for colocalization of farnesyl diphosphate synthase and farnesene synthase in S. cerevisiae. Different parameters were modulated to improve the system, and the enzyme:scaffold ratio was most critical for its functionality. Ultimately, the yield of farnesene on glucose YSFar could be improved by 135% in fed-batch cultivations using a 2-site affibody scaffold. The scaffolding strategy was then extended to a three-enzyme polyhydroxybutyrate (PHB) pathway, heterologously expressed in E. coli. Within a narrow range of enzyme and scaffold induction, the affibody tagging and scaffolding increased PHB production 7-fold. This work demonstrates how the versatile affibody can be used for metabolic engineering purposes. PMID- 27560950 TI - Tissue- and Time-Specific Expression of Otherwise Identical tRNA Genes. AB - Codon usage bias affects protein translation because tRNAs that recognize synonymous codons differ in their abundance. Although the current dogma states that tRNA expression is exclusively regulated by intrinsic control elements (A- and B-box sequences), we revealed, using a reporter that monitors the levels of individual tRNA genes in Caenorhabditis elegans, that eight tryptophan tRNA genes, 100% identical in sequence, are expressed in different tissues and change their expression dynamically. Furthermore, the expression levels of the sup-7 tRNA gene at day 6 were found to predict the animal's lifespan. We discovered that the expression of tRNAs that reside within introns of protein-coding genes is affected by the host gene's promoter. Pairing between specific Pol II genes and the tRNAs that are contained in their introns is most likely adaptive, since a genome-wide analysis revealed that the presence of specific intronic tRNAs within specific orthologous genes is conserved across Caenorhabditis species. PMID- 27560953 TI - Submucosal Abscess of the Esophagus Caused by Piriform Sinus Fistula Treated with Transoral Video Laryngoscopic Surgery. AB - Piriform sinus fistula (PSF) is a rare branchial anomaly that causes repetitive acute suppurative thyroiditis or deep neck abscess. The definitive treatment of PSF is open neck surgery. However, such surgery has a cosmetic problem and a high risk of recurrence. Furthermore, identifying the fistula is difficult due to previous repetitive infections. We report a case of esophageal submucosal abscess caused by PSF treated with endoscopic mucosal incision. The patient underwent transoral video laryngoscopic surgery (TOVS), and endoscopy as well as fluoroscopy revealed complete closure of PSF without any complication. TOVS is a novel surgical technique for the definitive treatment of PSF with esophageal submucosal abscess. PMID- 27560954 TI - Letter to the Editor: Author's Response. PMID- 27560955 TI - Letter to the Editor: Re: Decontamination of Anodized Implant Surface With Different Modalities for Peri-Implantitis Treatment: Lasers and Mechanical Debridement With Citric Acid. PMID- 27560956 TI - Letter to the Editor: Re: Investigation of the Association Between Cement Retention and Prevalent Peri-Implant Diseases: A Cross-Sectional Study. PMID- 27560957 TI - Letter to the Editor: Authors' Response. PMID- 27560958 TI - Perceptual Stability of the Lissajous Figure Is Modulated by the Speed of Illusory Rotation. AB - Lissajous figures represent ambiguous structure-from-motion stimuli rotating in depth and have proven to be a versatile tool to explore the cognitive and neural mechanisms underlying bistable perception. They are generated by the intersection of two sinusoids with perpendicular axes and increasing phase-shift whose frequency determines the speed of illusory 3D rotation. Recently, we found that Lissajous figures of higher shifting frequencies elicited longer perceptual phase durations and tentatively proposed a "representational momentum" account. In this study, our aim was twofold. First, we aimed to gather more behavioral evidence related to the perceptual dynamics of the Lissajous figure by simultaneously varying its shifting frequency and size. Using a conventional analysis, we investigated the effects of our experimental manipulations on transition probability (i.e., the probability that the current percept will change at the next critical stimulus configuration). Second, we sought to test the impact of our experimental factors on the occurrence of transitions in bistable perception by means of a Bayesian approach that can be used to directly quantify the impact of contextual cues on perceptual stability. We thereby estimated the implicit prediction of perceptual stability and how it is modulated by experimental manipulations. PMID- 27560959 TI - Ultrathin Zn2(OH)3VO3 Nanosheets: First Synthesis, Excellent Lithium-Storage Properties, and Investigation of Electrochemical Mechanism. AB - Nowadays, exploiting novel electrode materials is widely accepted as a key for meeting the growing demands of high-performance lithium ion batteries. Several transition-metal vanadates, which can in situ form an elastic buffer to adapt the volume expansion during lithium uptake/removal, have recently attracted much attention as anode materials, since they have high capacity and superior cycling stability. Herein, Zn2(OH)3VO3 nanostructures are successfully fabricated for the first time by a facile hydrothermal method and also first studied as lithium ion anode material. The ultrathin Zn2(OH)3VO3 nanosheets deliver a high reversible capacity close to 900 mAh g(-1) at a current density of 1 A g(-1) over 100 cycles. Even at a high current rate of 5 A g(-1), capacity retention as high as 83% (by compared with the second discharge capacity) is still obtained after 500 cycles, showing a high-rate capability. Moreover, we also carefully investigated the lithium-storage mechanism of Zn2(OH)3VO3, and corresponding results reveal that the Zn2(OH)3VO3 nanosheets have in situ transformed into ZnO nanoparticles anchoring on lithiated vanadium oxides matrix. The synergistic effect of zinc and vanadium oxides upon lithium ions intercalation and the stable conductive skeleton of amorphous lithiated vanadium oxides matrix both contribute to the excellent battery performance of Zn2(OH)3VO3 nanosheets. Finally, a full cell composed of lithiated Zn2(OH)3VO3/LiFePO4 with a high energy density of 293 Wh kg(-1) (vs total mass of active materials) at the current density of 100 mA g(-1) was successfully assembled, which could cycle well over 100 cycles with 79% capacity retention and also exhibit good rate stability. Thus, we believe that our research demonstrates a promising anode material for lithium ion batteries. PMID- 27560960 TI - The Cross-Sectional Association between Diet Quality and Depressive Symptomology amongst Fijian Adolescents. AB - OBJECTIVE: To examine the relationship between diet quality and depressive symptomology amongst a community-based sample of Fijian adolescents. METHODS: Participants included 7,237 adolescents (52.6% girls; mean age 15.6 years) at baseline (2005) and 2,948 (56% girls; mean age 17.4 years) at follow-up (2007/2008), from the Pacific Obesity Prevention in Communities Project. Intervention schools (n = 7) were selected from Nasinu, near Suva on the main Fijian island Viti Levu, and comparison schools (n = 11) were chosen from towns on the opposite, west side of the island. A dietary questionnaire was used to measure diet quality. Factor analysis clustered dietary variables into two unique and independent factors, referred to as healthy diet quality and unhealthy diet quality. Depressive symptomology was assessed via the emotional subscale of the Paediatric Quality of Life Inventory. Both measures were self-reported and self administered. Multiple linear regression was used to test cross-sectional associations (at baseline and follow-up) between diet quality and depressive symptomology. Variables controlled for included gender, age, ethnicity, study condition, BMI-z scores, and physical activity. FINDINGS: Strong, positive dose response associations between healthy diet and high emotional scores (lower depressive symptomology) were found in cross-sectional analyses at baseline and follow-up, among boys and girls. No association was found between emotional health and unhealthy diet. CONCLUSIONS: This study suggests that cross-sectional relationships exist between a high quality diet during adolescence and less depressive symptoms, however more evidence is required to determine if these two variables are linked causally. Trial population health strategies that use dietary interventions as a mechanism for mental health promotion provide an opportunity to further test these associations. If this is indeed a true relationship, these forms of interventions have the potential to be inexpensive and have substantial reach, especially in Low and Middle Income Countries. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000345381. PMID- 27560961 TI - Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease. AB - Numerous alpha-galactosidase A (alpha-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of alpha-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and alpha-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the alpha-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of alpha-gal A and genotype or clinical phenotypes were found for male patients. PMID- 27560962 TI - Identifying Ancient Settlement Patterns through LiDAR in the Mosquitia Region of Honduras. AB - The Mosquitia ecosystem of Honduras occupies the fulcrum between the American continents and as such constitutes a critical region for understanding past patterns of socio-political development and interaction. Heavy vegetation, rugged topography, and remoteness have limited scientific investigation. This paper presents prehistoric patterns of settlement and landuse for a critical valley within the Mosquitia derived from airborne LiDAR scanning and field investigation. We show that (i) though today the valley is a wilderness it was densely inhabited in the past; (ii) that this population was organized into a three-tiered system composed of 19 settlements dominated by a city; and, (iii) that this occupation was embedded within a human engineered landscape. We also add to a growing body of literature that demonstrates the utility of LiDAR as means for rapid cultural assessments in undocumented regions for analysis and conservation. Our ultimate hope is for our work to promote protections to safeguard the unique and critically endangered Mosquitia ecosystem and other similar areas in need of preservation. PMID- 27560963 TI - Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study. AB - BACKGROUND: Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery. MATERIALS AND METHODS: A Danish nationwide cohort study including all singletons born during 1997-2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. RESULTS: Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. CONCLUSIONS: Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section. PMID- 27560964 TI - Fermented Brown Rice Extract Stimulates BDNF Gene Transcription in C6 Glioma Cells: Possible Connection with HO-1 Expression. AB - Fermented brown rice with Aspergillus oryzae, designated as FBRA, is known to be commercially available dietary fiber-rich food, which is appreciated as prebiotics to improve intestinal microflora, and also shown to contain various biologically active substances including polyphenolic compounds. On the other hand, polyphenolic compounds have been suggested to stimulate the expression of brain-derived neurotrophic factor (BDNF) gene in connection with the expression of heme oxidase-1 (HO-1) gene in glial cells, thus resulting in the augmentation of BDNF production in the brain, thereby being anticipated to have a putative effect on the brain function. Then, the effect of FBRA extract on HO-1 and BDNF messenger ribonucleic acid (mRNA) levels in C6 glioma cells was examined, and the extract was shown to stimulate both HO-1 and BDNF gene transcription in the glioma cells. Further studies showed that the stimulatory effect of FBRA extract on BDNF gene transcription was almost completely suppressed by silencing HO-1 gene expression with an HO-1 antisense oligodeoxynucleotide and also inhibiting HO-1 activity with an inhibitor zinc protoporphyrin, thus suggesting that FBRA might have a potential ability to induce BDNF gene expression through HO-1 activity in glial cells. PMID- 27560965 TI - The Complete Chloroplast Genome Sequence of a Relict Conifer Glyptostrobus pensilis: Comparative Analysis and Insights into Dynamics of Chloroplast Genome Rearrangement in Cupressophytes and Pinaceae. AB - Glyptostrobus pensilis, belonging to the monotypic genus Glyptostrobus (Family: Cupressaceae), is an ancient conifer that is naturally distributed in low-lying wet areas. Here, we report the complete chloroplast (cp) genome sequence (132,239 bp) of G. pensilis. The G. pensilis cp genome is similar in gene content, organization and genome structure to the sequenced cp genomes from other cupressophytes, especially with respect to the loss of the inverted repeat region A (IRA). Through phylogenetic analysis, we demonstrated that the genus Glyptostrobus is closely related to the genus Cryptomeria, supporting previous findings based on physiological characteristics. Since IRs play an important role in stabilize cp genome and conifer cp genomes lost different IR regions after splitting in two clades (cupressophytes and Pinaceae), we performed cp genome rearrangement analysis and found more extensive cp genome rearrangements among the species of cupressophytes relative to Pinaceae. Additional repeat analysis indicated that cupressophytes cp genomes contained less potential functional repeats, especially in Cupressaceae, compared with Pinaceae. These results suggested that dynamics of cp genome rearrangement in conifers differed since the two clades, Pinaceae and cupressophytes, lost IR copies independently and developed different repeats to complement the residual IRs. In addition, we identified 170 perfect simple sequence repeats that will be useful in future research focusing on the evolution of genetic diversity and conservation of genetic variation for this endangered species in the wild. PMID- 27560966 TI - Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan. AB - OBJECTIVES: Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. METHODS: We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of >=4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. RESULTS: Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine promethazine-phenobarbital combination drug (Vegetamin(r)) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60-5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18 6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). CONCLUSION: These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose. PMID- 27560967 TI - Risk of Ischemic Stroke, Hemorrhagic Stroke, Bleeding, and Death in Patients Switching from Vitamin K Antagonist to Dabigatran after an Ablation. AB - BACKGROUND: Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation. METHODS: Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference. RESULTS: In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72-3.75) for bleeding and of 1.41 (0.66-3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40-14.5). CONCLUSION: Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding. PMID- 27560969 TI - A Look into the Cell: Honey Storage in Honey Bees, Apis mellifera. AB - Honey bees, Apis species, obtain carbohydrates from nectar and honeydew. These resources are ripened into honey in wax cells that are capped for long-term storage. These stores are used to overcome dearth periods when foraging is not possible. Despite the economic and ecological importance of honey, little is known about the processes of its production by workers. Here, we monitored the usage of storage cells and the ripening process of honey in free-flying A. mellifera colonies. We provided the colonies with solutions of different sugar concentrations to reflect the natural influx of nectar with varying quality. Since the amount of carbohydrates in a solution affects its density, we used computer tomography to measure the sugar concentration of cell content over time. The data show the occurrence of two cohorts of cells with different provisioning and ripening dynamics. The relocation of the content of many cells before final storage was part of the ripening process, because sugar concentration of the content removed was lower than that of content deposited. The results confirm the mixing of solutions of different concentrations in cells and show that honey is an inhomogeneous matrix. The last stage of ripening occurred when cell capping had already started, indicating a race against water absorption. The storage and ripening processes as well as resource use were context dependent because their dynamics changed with sugar concentration of the food. Our results support hypotheses regarding honey production proposed in earlier studies and provide new insights into the mechanisms involved. PMID- 27560970 TI - hEIDI: An Intuitive Application Tool To Organize and Treat Large-Scale Proteomics Data. AB - Advances in high-throughput proteomics have led to a rapid increase in the number, size, and complexity of the associated data sets. Managing and extracting reliable information from such large series of data sets require the use of dedicated software organized in a consistent pipeline to reduce, validate, exploit, and ultimately export data. The compilation of multiple mass spectrometry-based identification and quantification results obtained in the context of a large-scale project represents a real challenge for developers of bioinformatics solutions. In response to this challenge, we developed a dedicated software suite called hEIDI to manage and combine both identifications and semiquantitative data related to multiple LC-MS/MS analyses. This paper describes how, through a user-friendly interface, hEIDI can be used to compile analyses and retrieve lists of nonredundant protein groups. Moreover, hEIDI allows direct comparison of series of analyses, on the basis of protein groups, while ensuring consistent protein inference and also computing spectral counts. hEIDI ensures that validated results are compliant with MIAPE guidelines as all information related to samples and results is stored in appropriate databases. Thanks to the database structure, validated results generated within hEIDI can be easily exported in the PRIDE XML format for subsequent publication. hEIDI can be downloaded from http://biodev.extra.cea.fr/docs/heidi . PMID- 27560968 TI - Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific. AB - BACKGROUND: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use. METHODS: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression. RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. <=30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of >=60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018). CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region. PMID- 27560971 TI - A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome. AB - OBJECTIVE: Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS). METHODS: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS aged 2 to 6 years. RESULTS: Eighty-one subjects were screened for eligibility, and 57 were randomized to sertraline (27) or placebo (30). Two subjects from the sertraline arm and 3 from the placebo arm discontinued. Intent-to-treat analysis showed no difference from placebo on the primary outcomes: the Mullen Scales of Early Learning (MSEL) expressive language (EL) age equivalent and Clinical Global Impression Scale-Improvement. However, analyses of secondary measures showed significant improvements, particularly in motor and visual perceptual abilities and social participation. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events occurred. CONCLUSION: This randomized controlled trial of 6 months of sertraline treatment showed no primary benefit with respect to early EL development and global clinical improvement. However, in secondary exploratory analyses, there were significant improvements seen on motor and visual perceptual subtests, the cognitive T score sum on the MSEL, and on one measure of social participation on the Sensory Processing Measure-Preschool. Furthermore, post hoc analysis found significant improvement in early EL development as measured by the MSEL among children with autism spectrum disorder on sertraline. Treatment appears safe for this 6-month period in young children with FXS, but the authors do not know the long-term side effects of this treatment. These results warrant further studies of sertraline in young children with FXS using refined outcome measures as well as longer term follow-up studies to address long-term side effects of low-dose sertraline in early childhood. PMID- 27560972 TI - Modeling of Experimental Data Supports HIV Reactivation from Latency after Treatment Interruption on Average Once Every 5-8 Days. PMID- 27560973 TI - Coffee and green tea consumption in relation to brain tumor risk in a Japanese population. AB - Few prospective studies have investigated the etiology of brain tumor, especially among Asian populations. Both coffee and green tea are popular beverages, but their relation with brain tumor risk, particularly with glioma, has been inconsistent in epidemiological studies. In this study, we evaluated the association between coffee and greed tea intake and brain tumor risk in a Japanese population. We evaluated a cohort of 106,324 subjects (50,438 men and 55,886 women) in the Japan Public Health Center-Based Prospective Study (JPHC Study). Subjects were followed from 1990 for Cohort I and 1993 for Cohort II until December 31, 2012. One hundred and fifty-seven (70 men and 87 women) newly diagnosed cases of brain tumor were identified during the study period. Hazard ratio (HR) and 95% confidence intervals (95%CIs) for the association between coffee or green tea consumption and brain tumor risk were assessed using a Cox proportional hazards regression model. We found a significant inverse association between coffee consumption and brain tumor risk in both total subjects (>=3 cups/day; HR = 0.47, 95%CI = 0.22-0.98) and in women (>=3 cups/day; HR = 0.24, 95%CI = 0.06-0.99), although the number of cases in the highest category was small. Furthermore, glioma risk tended to decrease with higher coffee consumption (>=3 cups/day; HR = 0.54, 95%CI = 0.16-1.80). No association was seen between green tea and brain tumor risk. In conclusion, our study suggested that coffee consumption might reduce the risk of brain tumor, including that of glioma, in the Japanese population. PMID- 27560974 TI - ASAIO Top Rated Journal and Highlights of the 62nd ASAIO Conference. PMID- 27560975 TI - Correction: Local versus Generalized Phenotypes in Two Sympatric Aurelia Species: Understanding Jellyfish Ecology Using Genetics and Morphometrics. AB - [This corrects the article DOI: 10.1371/journal.pone.0156588.]. PMID- 27560977 TI - Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide Induced Oxidative Stress. AB - BACKGROUND: Oxidative stress is the predominant pathogenic mechanism of ischaemia reperfusion (IR) injury. The noble gas argon has been shown to alleviate oxidative stress-related myocardial and cerebral injury. The risk of lung IR injury is increased in some major surgeries, reducing clinical outcome. However, no study has examined the lung-protective efficacy of argon preconditioning. The present study investigated the protective effects of argon preconditioning on airway epithelial cells exposed to hydrogen peroxide (H2O2) to induce oxidative stress. METHODS: A549 airway epithelial cells were treated with a cytotoxic concentration of H2O2 after exposure to standard air or 30 or 50% argon/21% oxygen/5% carbon dioxide/rest nitrogen for 30, 45 or 180 min. Cells were stained with annexin V/propidium iodide, and apoptosis was evaluated by fluorescence activated cell sorting. Protective signalling pathways activated by argon exposure were identified by Western blot analysis for phosphorylated candidate molecules of the mitogen-activated protein kinase and protein kinase B (Akt) pathways. RESULTS: Preconditioning with 50% argon for 30, 45 and 180 min and 30% argon for 180 min caused significant protection of A549 cells against H2O2 induced apoptosis, with increases in cellular viability of 5-47% (p < 0.0001). A small adverse effect was also observed, which presented as a 12-15% increase in cellular necrosis in argon-treated groups. Argon exposure resulted in early activation of c-Jun N-terminal kinase (JNK) and p38, peaking 10- 30 min after the start of preconditioning, and delayed activation of the extracellular signal regulated kinase 1/2 (ERK1/2) pathway, peaking after 60-90 min. CONCLUSIONS: Argon preconditioning protects airway epithelial cells from H2O2-induced apoptotic cell death. Argon activates the JNK, p38, and ERK1/2 pathways, but not the Akt pathway. The cytoprotective properties of argon suggest possible prophylactic applications in surgery-related IR injury of the lungs. PMID- 27560976 TI - Glucose Sensor MdHXK1 Phosphorylates and Stabilizes MdbHLH3 to Promote Anthocyanin Biosynthesis in Apple. AB - Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF) MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3. Moreover, phosphorylation modification stabilized MdbHLH3 protein and enhanced its transcription of the anthocyanin biosynthesis genes, thereby increasing anthocyanin biosynthesis. Finally, a series of transgenic analyses in apple calli and fruits demonstrated that MdHXK1 controlled glucose-induced anthocyanin accumulation at least partially, if not completely, via regulating MdbHLH3. Overall, our findings provide new insights into the mechanism of the glucose sensor HXK1 modulation of anthocyanin accumulation, which occur by directly regulating the anthocyanin-related bHLH TFs in response to a glucose signal in plants. PMID- 27560978 TI - Functional Role of Native and Invasive Filter-Feeders, and the Effect of Parasites: Learning from Hypersaline Ecosystems. AB - Filter-feeding organisms are often keystone species with a major influence on the dynamics of aquatic ecosystems. Studies of filtering rates in such taxa are therefore vital in order to understand ecosystem functioning and the impact of natural and anthropogenic stressors such as parasites, climate warming and invasive species. Brine shrimps Artemia spp. are the dominant grazers in hypersaline systems and are a good example of such keystone taxa. Hypersaline ecosystems are relatively simplified environments compared with much more complex freshwater and marine ecosystems, making them suitable model systems to address these questions. The aim of this study was to compare feeding rates at different salinities and temperatures between clonal A. parthenogenetica (native to Eurasia and Africa) and the invasive American brine shrimp A. franciscana, which is excluding native Artemia from many localities. We considered how differences observed in laboratory experiments upscale at the ecosystem level across both spatial and temporal scales (as indicated by chlorophyll-a concentration and turbidity). In laboratory experiments, feeding rates increased at higher temperatures and salinities in both Artemia species and sexes, whilst A. franciscana consistently fed at higher rates. A field study of temporal dynamics revealed significantly higher concentrations of chlorophyll-a in sites occupied by A. parthenogenetica, supporting our experimental findings. Artemia parthenogenetica density and biomass were negatively correlated with chlorophyll a concentration at the spatial scale. We also tested the effect of cestode parasites, which are highly prevalent in native Artemia but much rarer in the invasive species. The cestodes Flamingolepis liguloides and Anomotaenia tringae decreased feeding rates in native Artemia, whilst Confluaria podicipina had no significant effect. Total parasite prevalence was positively correlated with turbidity. Overall, parasites are likely to reduce feeding rates in the field, and their negative impact on host fecundity is likely to exacerbate the difference between grazing rates of native and alien Artemia populations at the ecosystem level. The results of this study provide evidence for the first time that the replacement of native Artemia by A. franciscana may have major consequences for the functioning of hypersaline ecosystems. The strong effect of parasites on feeding rate underlines the importance of taking parasites into account in order to improve our understanding of the functioning of aquatic ecosystems. PMID- 27560979 TI - Multiple facets of p53 in senescence induction and maintenance. AB - Cellular senescence is a state of durable cell cycle arrest with metabolic activities distinct from those of the proliferative state. Since senescence was originally reported to be induced by various genotoxic stressors, such as telomere erosion and oncogenic signaling, it has been proposed to play a pivotal role in aging-related changes and as an antitumorigenic barrier in vivo. However, the mechanisms underlying its induction and maintenance remain entirely elusive. We have recently found that abrupt activation of p53 at G2 results in a cell skipping mitosis and subsequently undergoing senescence. Surprisingly, we have also found that downregulation of p53 by SCFFbxo22 is crucial for the induction of a senescence-associated phenotype. In this review, we provide an overview of recent advances in understanding the mechanisms underlying the timing and magnitude of activation of p53 during senescence. PMID- 27560980 TI - Assessing Weather-Yield Relationships in Rice at Local Scale Using Data Mining Approaches. AB - Seasonal and inter-annual climate variability have become important issues for farmers, and climate change has been shown to increase them. Simultaneously farmers and agricultural organizations are increasingly collecting observational data about in situ crop performance. Agriculture thus needs new tools to cope with changing environmental conditions and to take advantage of these data. Data mining techniques make it possible to extract embedded knowledge associated with farmer experiences from these large observational datasets in order to identify best practices for adapting to climate variability. We introduce new approaches through a case study on irrigated and rainfed rice in Colombia. Preexisting observational datasets of commercial harvest records were combined with in situ daily weather series. Using Conditional Inference Forest and clustering techniques, we assessed the relationships between climatic factors and crop yield variability at the local scale for specific cultivars and growth stages. The analysis showed clear relationships in the various location-cultivar combinations, with climatic factors explaining 6 to 46% of spatiotemporal variability in yield, and with crop responses to weather being non-linear and cultivar-specific. Climatic factors affected cultivars differently during each stage of development. For instance, one cultivar was affected by high nighttime temperatures in the reproductive stage but responded positively to accumulated solar radiation during the ripening stage. Another was affected by high nighttime temperatures during both the vegetative and reproductive stages. Clustering of the weather patterns corresponding to individual cropping events revealed different groups of weather patterns for irrigated and rainfed systems with contrasting yield levels. Best-suited cultivars were identified for some weather patterns, making weather-site-specific recommendations possible. This study illustrates the potential of data mining for adding value to existing observational data in agriculture by allowing embedded knowledge to be quickly leveraged. It generates site-specific information on cultivar response to climatic factors and supports on-farm management decisions for adaptation to climate variability. PMID- 27560981 TI - Prenatal exposure to chlordecone, gestational weight gain, and birth weight in a Guadeloupean birth cohort. AB - BACKGROUND: Chlordecone is a persistent organochlorine insecticide with well defined estrogenic properties. It was intensively used in the French West Indies until 1993 to control the banana root borer. Because of the long-term contamination of soils and water, the population is currently exposed to chlordecone through food consumption. Chlordecone has been found in the blood of pregnant women and in cord blood. It has been shown to be an endocrine-disrupting chemical and exposure during pregnancy may affect fetal growth. OBJECTIVES: The objective of our study was to examine the association between prenatal exposure to chlordecone and fetal growth based on the TIMOUN birth cohort conducted in Guadeloupe, with a focus on the potential modification of this relationship by maternal body mass index (BMI) and gestational weight gain (GWG). METHODS: Chlordecone was determined in cord plasma at birth in 593 babies. Birth weight was the indicator of fetal growth. Maternal pre-pregnancy BMI and GWG were determined. Adherence to GWG recommendations of the US Institute of Medicine based on maternal pre-pregnancy BMI was assessed. Birth weight was analyzed relative to cord blood chlordecone levels using linear and non-linear regression models. RESULTS: Overall chlordecone in cord blood was not associated with birth weight, but we found an interaction between chlordecone exposure with GWG and adherence to GWG recommendations. After stratification by GWG, we found a significant U-shaped association between birth weight and chlordecone exposure, within the upper quartiles of GWG or excessive GWG. CONCLUSION: Chlordecone exposure may affect fetal growth, particularly when excessive GWG is present. PMID- 27560982 TI - Genome-Wide Identification, Evolutionary Analysis and Expression Profiles of LATERAL ORGAN BOUNDARIES DOMAIN Gene Family in Lotus japonicus and Medicago truncatula. AB - The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) gene family has been well-studied in Arabidopsis and play crucial roles in the diverse growth and development processes including establishment and maintenance of boundary of developmental lateral organs. In this study we identified and characterized 38 LBD genes in Lotus japonicus (LjLBD) and 57 LBD genes in Medicago truncatula (MtLBD), both of which are model legume plants that have some specific development features absent in Arabidopsis. The phylogenetic relationships, their locations in the genome, genes structure and conserved motifs were examined. The results revealed that all LjLBD and MtLBD genes could be distinctly divided into two classes: Class I and II. The evolutionary analysis showed that Type I functional divergence with some significantly site-specific shifts may be the main force for the divergence between Class I and Class II. In addition, the expression patterns of LjLBD genes uncovered the diverse functions in plant development. Interestingly, we found that two LjLBD proteins that were highly expressed during compound leaf and pulvinus development, can interact via yeast two-hybrid assays. Taken together, our findings provide an evolutionary and genetic foundation in further understanding the molecular basis of LBD gene family in general, specifically in L. japonicus and M. truncatula. PMID- 27560984 TI - Frontal negativity: An electrophysiological index of interpersonal guilt. AB - The present study aimed to reveal the temporal course and electrophysiological correlates of interpersonal guilt. Human participants were asked to perform multiple rounds of a dot-estimation task with their partners, while event-related potential being recorded. The paired participants were informed that they would win money if both responded correctly; otherwise, both of them would lose money. The feeling of guilt in Self-Wrong condition (SW) was significantly higher than that in Both-Wrong and Partner-Wrong conditions. At approximately 350 ms after the onset of feedback presentation, greater negativities were observed in the frontal regions in the guilt condition (i.e., SW) than those in the non-guilt condition. The guilt-modulated frontal negativity might reflect the interactions of self-reflection, condemnation, and negative emotion. PMID- 27560983 TI - Monoclonal antibodies against pools of mono- and polyacetylated peptides selectively recognize acetylated lysines within the context of the original antigen. AB - Post-translational modifications (PTMs) strongly influence the structure and function of proteins. Lysine side chain acetylation is one of the most widespread PTMs, and it plays a major role in several physiological and pathological mechanisms. Protein acetylation may be detected by mass spectrometry (MS), but the use of monoclonal antibodies (mAbs) is a useful and cheaper option. Here, we explored the feasibility of generating mAbs against single or multiple acetylations within the context of a specific sequence. As a model, we used the unstructured N-terminal domain of APE1, which is acetylated on Lys27, Lys31, Lys32 and Lys35. As immunogen, we used a peptide mixture containing all combinations of single or multi-acetylated variants encompassing the 24-39 protein region. Targeted screening of the resulting clones yielded mAbs that bind with high affinity to only the acetylated APE1 peptides and the acetylated protein. No binding was seen with the non-acetylated variant or unrelated acetylated peptides and proteins, suggesting a high specificity for the APE1 acetylated molecules. MAbs could not finely discriminate between the differently acetylated variants; however, they specifically bound the acetylated protein in mammalian cell extracts and in intact cells and tissue slices from both breast cancers and from a patient affected by idiopathic dilated cardiomyopathy. The data suggest that our approach is a rapid and cost-effective method to generate mAbs against specific proteins modified by multiple acetylations or other PTMs. PMID- 27560985 TI - Intermittent Androgen Deprivation Therapy-An Important Treatment Option for Prostate Cancer. PMID- 27560986 TI - Whole Genome Sequencing Identifies a Missense Mutation in HES7 Associated with Short Tails in Asian Domestic Cats. AB - Domestic cats exhibit abundant variations in tail morphology and serve as an excellent model to study the development and evolution of vertebrate tails. Cats with shortened and kinked tails were first recorded in the Malayan archipelago by Charles Darwin in 1868 and remain quite common today in Southeast and East Asia. To elucidate the genetic basis of short tails in Asian cats, we built a pedigree of 13 cats segregating at the trait with a founder from southern China and performed linkage mapping based on whole genome sequencing data from the pedigree. The short-tailed trait was mapped to a 5.6 Mb region of Chr E1, within which the substitution c. 5T > C in the somite segmentation-related gene HES7 was identified as the causal mutation resulting in a missense change (p.V2A). Validation in 245 unrelated cats confirmed the correlation between HES7-c. 5T > C and Chinese short-tailed feral cats as well as the Japanese Bobtail breed, indicating a common genetic basis of the two. In addition, some of our sampled kinked-tailed cats could not be explained by either HES7 or the Manx-related T box, suggesting at least three independent events in the evolution of domestic cats giving rise to short-tailed traits. PMID- 27560987 TI - Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients. AB - Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 DeltaG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 DeltaG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 DeltaG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 DeltaG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 DeltaG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients. PMID- 27560988 TI - DNA damage protective effect of honey-sweetened cashew apple nectar in Drosophila melanogaster. AB - Fruits and derivatives, such as juices, are complex mixtures of chemicals, some of which may have mutagenic and/or carcinogenic potential, while others may have antimutagenic and/or anticancer activities. The modulating effects of honey sweetened cashew apple nectar (HSCAN), on somatic mutation and recombination induced by ethyl methanesulfonate (EMS) and mitomycin C (MMC) were evaluated with the wing spot test in Drosophila melanogaster using co- and post-treatment protocols. Additionally, the antimutagenic activity of two HSCAN components, cashew apple pulp and honey, in MMC-induced DNA damage was also investigated. HSCAN reduced the mutagenic activity of both EMS and MMC in the co-treatment protocol, but had a co-mutagenic effect when post-administered. Similar results were also observed with honey on MMC mutagenic activity. Cashew apple pulp was effective in exerting protective or enhancing effects on the MMC mutagenicity, depending on the administration protocol and concentration used. Overall, these results indicate that HSCAN, cashew apple and honey seem capable of modulating not only the events that precede the induced DNA damages, but also the Drosophila DNA repair processes involved in the correction of EMS and MMC-induced damages. PMID- 27560989 TI - Molecular assessment of the phylogeny and biogeography of a recently diversified endemic group of South American canids (Mammalia: Carnivora: Canidae). AB - To investigate the evolution and biogeography of an endemic group of South American foxes, we examined mitochondrial DNA control region sequences for 118 individuals belonging to all six extant species of the genus Lycalopex. Phylogenetic and molecular dating analyses supported the inference that this genus has undergone a very recent and rapid radiation, stemming from a common ancestor that lived ca. 1 million years ago. The Brazilian endemic L. vetulus was supported as the most basal species in this genus, whereas the most internal group is comprised by the recently diverged (ca. 350,000 years ago) Andean/Patagonian species L. griseus and L. culpaeus. We discuss the inferred phylogenetic relationships and divergence times in the context of the current geographic distributions of these species, and the likely effects of Pleistocene climatic changes on the biogeography of this group. Furthermore, a remarkable finding was the identification of multiple individuals classified as L. gymnocercus bearing mtDNA haplotypes clearly belonging to L. griseus, sampled in regions where the latter is not known to occur. At a minimum, this result implies the need to clarify the present-day geographic distribution of each of these fox species, while it may also indicate an ongoing hybridization process between them. Future testing of this hypothesis with in-depth analyses of these populations is thus a priority for understanding the history, evolutionary dynamics and present-day composition of this endemic Neotropical genus. PMID- 27560990 TI - The catalase gene family in cucumber: genome-wide identification and organization. AB - Catalase (CAT) is a common antioxidant enzyme in almost all living organisms. Currently, detailed reports on cucumber (Cucumis sativus L.) CAT (CsCAT) genes and tissue expression profiling are limited. In the present study, four candidate CsCAT genes were identified in cucumber. Phylogenetic analysis indicated that CsCAT1-CsCAT3 are closely related to Arabidopsis AtCAT1-AtCAT3, but no obvious counterpart was observed for CsCAT4. Intron/exon structure analysis revealed that only one of the 15 positions was completely conserved. Motif analysis showed that, unlike the CAT genes of other species, none of CsCAT genes contained all 10 motifs. Expression data showed that transcripts of all of the CsCAT genes, except CsCAT4, were detected in five tissues. Moreover, their transcription levels displayed differences under different stress treatments. PMID- 27560991 TI - Molecular and biochemical characterization of carbonic anhydrases of Paracoccidioides. AB - Carbonic anhydrases (CA) belong to the family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate. In the present work, we characterized the cDNAs of four Paracoccidioides CAs (CA1, CA2, CA3, and CA4). In the presence of CO2, there was not a significant increase in fungal ca1, ca2 and ca4 gene expression. The ca1 transcript was induced during the mycelium-to-yeast transition, while ca2 and ca4 gene expression was much higher in yeast cells, when compared to mycelium and mycelium-to-yeast transition. The ca1 transcript was induced in yeast cells recovered directly from liver and spleen of infected mice, while transcripts for ca2 and ca4 were down regulated. Recombinant CA1 (rCA1) and CA4 (rCA4), with 33 kDa and 32 kDa respectively, were obtained from bacteria. The enzymes rCA1 (beta-class) and rCA4 (alpha-class) were characterized regarding pH, temperature, ions and amino acids addition influence. Both enzymes were stable at pHs 7.5-8.5 and temperatures of 30-35 degrees C. The enzymes were dramatically inhibited by Hg+2 and activated by Zn+2, while only rCA4 was stimulated by Fe2+. Among the amino acids tested (all in L configuration), arginine, lysine, tryptophan and histidine enhanced residual activity of rCA1 and rCA4. PMID- 27560993 TI - A new perspective on the electron transfer: recovering the Butler-Volmer equation in non-equilibrium thermodynamics. AB - Electron transfer reactions are commonly described by the phenomenological Butler Volmer equation which has its origin in kinetic theories. The Butler-Volmer equation relates interfacial reaction rates to bulk quantities like the electrostatic potential and electrolyte concentrations. Although the general structure of the equation is well accepted, for modern electrochemical systems like batteries and fuel cells there is still intensive discussion about the specific dependencies of the coefficients. A general guideline for the derivation of Butler-Volmer type equations is missing in the literature. We derive very general relations of Butler-Volmer structure which are based on a rigorous non equilibrium thermodynamic model and allow for adaption to a wide variety of electrochemical systems. We discuss the application of the new thermodynamic approach to different scenarios like the classical electron transfer reactions at metal electrodes and the intercalation process in lithium-iron-phosphate electrodes. Furthermore we show that under appropriate conditions also adsorption processes can lead to Butler-Volmer equations. We illustrate the application of our theory by a strongly simplified example of electroplating. PMID- 27560992 TI - Molecular cloning and characterization of a novel freezing-inducible DREB1/CBF transcription factor gene in boreal plant Iceland poppy (Papaver nudicaule). AB - DREB1 of the AP2/ERF superfamily plays a key role in the regulation of plant response to low temperatures. In this study, a novel DREB1/CBF transcription factor, PnDREB1, was isolated from Iceland poppy (Papaver nudicaule), a plant adaptive to low temperature environments. It is homologous to the known DREB1s of Arabidopsis and other plant species. It also shares similar 3D structure, and conserved and functionally important motifs with DREB1s of Arabidopsis. The phylogenetic analysis indicated that the AP2 domain of PnDREB1 is similar to those of Glycine max, Medicago truncatula, and M. sativa. PnDREB1 is constitutively expressed in diverse tissues and is increased in roots. qPCR analyses indicated that PnDREB1 is significantly induced by freezing treatment as well as by abscissic acid. The expression levels induced by freezing treatment were higher in the variety with higher degree of freezing tolerance. These results suggested that PnDREB1 is a novel and functional DREB1 transcription factor involved in freezing response and possibly in other abiotic stresses. Furthermore, the freezing-induction could be suppressed by exogenous gibberellins acid, indicating that PnDREB1 might play some role in the GA signaling transduction pathway. This study provides a basis for better understanding the roles of DREB1 in adaption of Iceland poppy to low temperatures. PMID- 27560994 TI - Hypothetical evaluations of positive and negative alcohol consequences in adolescents across various levels of drinking experience. AB - Research supports the importance of the subjective evaluation of alcohol-related consequences, and theory suggests that these evaluations may depend on one's prior experience. The goal of the present study was to understand how adolescents subjectively evaluate the potential negative and positive consequences of drinking and to test the hypothesis that evaluations differ as a function of personal experience with alcohol use and consequences. Participants were 697 adolescents (55% female) who completed online surveys assessing lifetime drinking experience and hypothetical evaluations of 13 negative and 9 positive consequences. Never having consumed a full drink of alcohol (vs. having consumed a full drink, but not having negative consequences) was significantly associated with higher mean negative evaluations and lower mean positive evaluations. Those who had a full drink (vs. those who had not) rated close to half of the negative consequence items as significantly less bothersome, and all of the positive consequences as significantly more enjoyable. However, there was little evidence in this sample that evaluations differ between drinkers with and without experience with negative consequences. Overall, findings suggest that youth who have experience with simply consuming alcohol may place more value on the positive and less value on some of the negative consequences of drinking, which has the potential to impact decisions to continue to drink. Longitudinal research uncovering the direction of evaluation-experience effects and mechanisms other than consequence experience, are essential next steps. (PsycINFO Database Record PMID- 27560995 TI - Within-person associations between daily motivation and self-efficacy and drinking among problem drinkers in treatment. AB - Gaining a better understanding of the change process holds promise to improve alcohol treatment. Ecological momentary assessment (EMA) coupled with intensive longitudinal data (ILD) approaches have been proposed as promising methods that can advance change process research but have been used infrequently in alcohol use disorder (AUD) treatment research. The current study used these approaches to examine the within-person associations of motivation and self-efficacy and drinking among treatment-seeking problem drinkers. Participants (N = 96) received daily EMA surveys before, during, and after treatment for 7 weeks spread over a 9 month period. Multilevel modeling was used to test the within-person relationships between the change processes and drinking, controlling for between person associations and prior drinking. Results indicated that daily fluctuations in motivation and self-efficacy significantly predicted drinking over the next 24 hours; however, several theory-driven hypotheses regarding factors that might moderate that relationship were not supported. Overall, results support the advantages of EMA and ILD as methods that can advance AUD treatment research. (PsycINFO Database Record PMID- 27560996 TI - Intracultural accusations of assimilation and alcohol use severity among Hispanic emerging adults: Moderating effects of acculturation, enculturation, and gender. AB - Individuals, including Hispanics, tend to drink most heavily during emerging adulthood (ages 18-25 years old). Research has suggested that intercultural stressors (e.g., ethnic discrimination) may increase levels of alcohol use among Hispanics. However, the relationship between intracultural stressors (e.g., accusations of assimilation-when Hispanics accuse a member of their heritage group of acculturating to U.S. culture) and alcohol use has been examined to a lesser extent. Accordingly, the present study aimed to (a) examine the association between family accusations of assimilation and alcohol use severity; and (b) examine if acculturation domains, enculturation domains, and gender moderated that association. A hierarchical multiple regression and moderation analyses were conducted on a cross-sectional sample of 181 Hispanic emerging adults. Results indicated that higher family accusations of assimilation were associated with higher levels of alcohol use severity (beta = .18, p < .05), and all variables entered in the model accounted for DeltaR2 = 15.1% of the variance of alcohol use severity. A moderation analysis indicated that higher family accusations of assimilation were associated with higher alcohol use severity among men, but not women. Of the four acculturation/enculturation domains, none had a moderation effect. However, there was a statistically significant three-way interaction among family accusations of assimilation, gender, and affective enculturation. This three-way interaction suggests that among men, higher family accusations of assimilation were associated with higher alcohol use severity at lower levels of affective enculturation. This study addresses a literature gap on intracultural stressors and substance use among Hispanics, and discusses recommendations for future research. (PsycINFO Database Record PMID- 27560997 TI - Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males. AB - BACKGROUND: Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. PREDICTOR: Uric acid levels at renal biopsy. OUTCOMES: The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". MEASUREMENTS: The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. RESULTS: An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. LIMITATIONS: A cohort analyzed retorospectively. CONCLUSIONS: This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID- 27560998 TI - Presence of pharmaceuticals in the Lis river (Portugal): Sources, fate and seasonal variation. AB - The occurrence of 33 pharmaceuticals and metabolites was evaluated along the Lis river and in the influents and effluents of two wastewater treatment plants (WWTPs) located along the river. Results indicate that pharmaceuticals, such as ibuprofen, ketoprofen, carbamazepine and fluoxetine, and the metabolite salicylic acid are widespread along the Lis river, showing 100% of detection frequency, at levels up to 1.3MUgL-1. The number of molecules detected increased along the river, with 11 molecules in the source, 15 upstream WWTP 1, 16 downstream WWTP 1 and upstream WWTP 2 and 19 downstream WWTP 2. The highest concentrations were often found downstream near the river mouth. Different possible sources of contamination of the Lis river were identified, namely WWTP effluents, untreated wastewaters and livestock production. Nevertheless, the discharge of WWTP effluents appeared to be the most pronounced, given that, in general, it was noticed an increase in the concentration of pharmaceuticals downstream of the WWTPs. WWTP effluents contributed with a total mass load of pharmaceuticals into the Lis river between 470 and 2317mg/d/1000 inhabitants. Non-steroidal anti inflammatory drugs/analgesics were the therapeutic group with a high contribution to the total mass load of pharmaceuticals entering the Lis river, followed by psychiatric drugs and antibiotics. No seasonal variation was observed for the detected concentrations of pharmaceuticals. At the levels detected in the Lis river, sulfamethoxazole, clarithromycin, azithromycin and ibuprofen showed to have potential risk for aquatic organisms. These findings show that further studies embracing different environmental compartments (water, sediment and biota) are needed, in order to evaluate the partition/distribution of pharmaceuticals, their metabolites and transformation products in the environment as well as to predict their possible impact to non-target organisms and, in a last instance, to human health. PMID- 27560999 TI - Tumor Touch Imprints as Source for Whole Genome Analysis of Neuroblastoma Tumors. AB - INTRODUCTION: Tumor touch imprints (TTIs) are routinely used for the molecular diagnosis of neuroblastomas by interphase fluorescence in-situ hybridization (I FISH). However, in order to facilitate a comprehensive, up-to-date molecular diagnosis of neuroblastomas and to identify new markers to refine risk and therapy stratification methods, whole genome approaches are needed. We examined the applicability of an ultra-high density SNP array platform that identifies copy number changes of varying sizes down to a few exons for the detection of genomic changes in tumor DNA extracted from TTIs. MATERIAL AND METHODS: DNAs were extracted from TTIs of 46 neuroblastoma and 4 other pediatric tumors. The DNAs were analyzed on the Cytoscan HD SNP array platform to evaluate numerical and structural genomic aberrations. The quality of the data obtained from TTIs was compared to that from randomly chosen fresh or fresh frozen solid tumors (n = 212) and I-FISH validation was performed. RESULTS: SNP array profiles were obtained from 48 (out of 50) TTI DNAs of which 47 showed genomic aberrations. The high marker density allowed for single gene analysis, e.g. loss of nine exons in the ATRX gene and the visualization of chromothripsis. Data quality was comparable to fresh or fresh frozen tumor SNP profiles. SNP array results were confirmed by I-FISH. CONCLUSION: TTIs are an excellent source for SNP array processing with the advantage of simple handling, distribution and storage of tumor tissue on glass slides. The minimal amount of tumor tissue needed to analyze whole genomes makes TTIs an economic surrogate source in the molecular diagnostic work up of tumor samples. PMID- 27561000 TI - Evaluation of Postoperative Povidone-Iodine in Adjustable Suture Strabismus Surgery to Reduce Suture Colonization: A Randomized Clinical Trial. AB - Importance: Although the association between suture colonization and postoperative infections remains hypothetical, measures to reduce perioperative suture colonization may minimize postoperative infections. The suture colonization rate in adjustable suture strabismus surgery is not well defined, and the effect of povidone-iodine use on suture colonization is unknown. Objective: To assess whether povidone-iodine application at the end of adjustable suture strabismus surgery decreases the suture colonization rate. Design, Setting, and Participants: In this randomized clinical trial designed in 2015 and performed from June 1 through October 31, 2015, a total of 65 adjustable and 43 control suture specimens from 65 demographically similar adults undergoing adjustable suture strabismus surgery were studied. A random sampling assigned participants into group 1 (with povidone-iodine) or group 2 (without povidone iodine) at the end of surgery. A control suture specimen was obtained if ipsilateral nonadjustable surgery was performed. Both groups received antibiotic ointment at the end of the procedure. No patients refused participation or withdrew. Data analysis was performed from October 1 to December 31, 2015. Observers were unaware of patient grouping. Interventions: One drop of 5% povidone-iodine directly over the sliding noose of the adjustable suture at the end of surgery. Main Outcomes and Measures: The suture colonization rate after adjustment in group 1, group 2, and the control group. Results: Of 65 adults undergoing surgery, there were 17 men (49%) and 18 women (51%) in group 1 and 10 men (33%) and 20 women (67%) in group 2, as well as 20 men (47%) and 23 women (53%) in the control group. The mean (SD) age of the patients was 48.5 (16.8) years in group 1, 46.6 (18.1) years in group 2, and 47.7 (17.0) years in the control group. There was no difference in the colonization rate between group 1 (57%) and group 2 (47%) (relative risk [RR], 1.1; 95% CI, 0.6-1.7; P = .80), group 1 and the control group (44%) (RR, 1.0; 95% CI, 0.5-1.8; P > .99), or group 2 and the control group (RR, 1.3; 95% CI, 0.8-2.1; P = .62). Eleven bacterial species were identified. Staphylococcus epidermidis was the predominant isolate (40 of 56 [71%]). A longer interval between the end of surgery and adjustment was associated with higher culture positivity (6.3 hours in positive vs 4.4 hours in negative cultures, P = .001); however, there was no difference in bacterial growth between the groups. No adverse effects of povidone-iodine were observed. Conclusions and Relevance: This study was not able to demonstrate that povidone iodine at the end of adjustable suture strabismus surgery reduces the suture colonization rate. Trial Registration: clinicaltrials.gov Identifier: NCT02424357. PMID- 27561001 TI - Product Aspect Clustering by Incorporating Background Knowledge for Opinion Mining. AB - Product aspect recognition is a key task in fine-grained opinion mining. Current methods primarily focus on the extraction of aspects from the product reviews. However, it is also important to cluster synonymous extracted aspects into the same category. In this paper, we focus on the problem of product aspect clustering. The primary challenge is to properly cluster and generalize aspects that have similar meanings but different representations. To address this problem, we learn two types of background knowledge for each extracted aspect based on two types of effective aspect relations: relevant aspect relations and irrelevant aspect relations, which describe two different types of relationships between two aspects. Based on these two types of relationships, we can assign many relevant and irrelevant aspects into two different sets as the background knowledge to describe each product aspect. To obtain abundant background knowledge for each product aspect, we can enrich the available information with background knowledge from the Web. Then, we design a hierarchical clustering algorithm to cluster these aspects into different groups, in which aspect similarity is computed using the relevant and irrelevant aspect sets for each product aspect. Experimental results obtained in both camera and mobile phone domains demonstrate that the proposed product aspect clustering method based on two types of background knowledge performs better than the baseline approach without the use of background knowledge. Moreover, the experimental results also indicate that expanding the available background knowledge using the Web is feasible. PMID- 27561002 TI - Time to Reassess the Cancer Compendia for Off-label Drug Coverage in Oncology. PMID- 27561003 TI - Cellular and molecular effects of yeast probiotics on cancer. AB - The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and beta-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti proliferative effects. PMID- 27561004 TI - Electrical and optoelectrical modification of cadmium sulfide nanobelts by low energy electron beam irradiation. AB - In this report, we describe a method for modifying electrical and optoelectrical properties of CdS nanobelts using low-energy (lower than 10 keV) e-beam irradiation in a scanning electron microscope. The electrical conductivity of the nanobelts was dramatically improved via the irradiation of e-beams. The modified conductivity of the nanobelts depends on the energy of the e-beam; it exhibits a larger photocurrent and higher external quantum efficiency but slower time response than that before the modification. A possible mechanism about the modification is the increase of electron accumulation (injected electrons) in the nanobelts due to e-beam irradiation. In addition, the optoelectrical modification could be caused by the trapped electrons in the nanobelts and the decrease of contact resistance between the nanobelts and metal electrodes induced by e-beam irradiation. The results of this work are significant for the in situ study of semiconductor nanostructures in the electron microscope. Besides, the method of electrical and optoelectrical modification presented here has potential application in electronics and optoelectronics. PMID- 27561005 TI - Visual Outcome and Patient Satisfaction of Low-Power-Added Multifocal Intraocular Lens. AB - PURPOSE: To evaluate visual outcome and patient satisfaction following implantation of multifocal intraocular lenses (IOLs) with a +1.5 diopters (D) addition compared with monofocal IOLs. METHODS: This prospective, nonrandomized, comparative case series involved 48 eyes (24 patients) who underwent cataract surgery with implantation of low-power-added multifocal IOLs (LS313-MF15; multifocal group) and 48 eyes (24 patients) with conventional monofocal IOLs (CTS204; monofocal group). Visual acuity (VA), defocus curves, refraction, contrast sensitivity, glare, ocular optical quality, and scores in questionnaire were assessed 6 months postoperatively. RESULTS: Uncorrected VA at intermediate and near distance tended to be better in the multifocal group, with significant differences at 50 cm (P=0.03). The defocus curve showed significantly different VA at vergences of -1.5 and -2.0 D (P=0.02 and P=0.03, respectively). Results of postoperative refraction, contrast sensitivity, glare, and optical quality were similar (P>0.05), although coma-like aberration was higher in the multifocal group (P=0.04). Despite of similar levels of visual disturbances (P>0.05), disturbances in activities and spectacle use at intermediate working distance were significantly less frequent in the multifocal group (P=0.03 and P=0.04, respectively). Multifocal group showed significantly greater overall satisfaction (P=0.02). CONCLUSIONS: Low-power-added multifocal IOLs yielded better intermediate and near vision without increasing optical phenomena compared with monofocal IOLs. PMID- 27561006 TI - Changes in Adherence to Non-Pharmacological Guidelines for Hypertension. AB - This study aimed to compare levels of adherence to non-pharmacological guidelines between patients with and without hypertension diagnoses, and examined temporal changes in adherence during recent decades. We used data from the Korean National Health and Nutrition Examination Survey (1998-2012), including 13,768 Korean hypertensive patients aged >= 30 years who were categorized according to the presence or absence of a hypertension diagnosis, based on blood pressure and self reported information. Adherence to the guidelines was calculated for 6 components, including dietary and lifestyle habits. A multivariable generalized linear regression model was used. The proportion of hypertensive patients aware of their condition increased from 33.4% in 1998 to 74.8% in 2012 (p < 0.001), although these increments plateaued during recent survey years. Patients with hypertension diagnoses were older, and more likely to be female,and have lower education levels than those without hypertension diagnoses, for most survey years. Overall adherence levels were poor (mean score 2 of 6), and levels of adherence to non-pharmacological habits did not significantly differ between patients with and without hypertension diagnoses. However, overall adherence levels improved significantly among patients with hypertension diagnoses: from 2.09 in 1998 to 2.27 in 2012 (p = 0.007), particularly regarding sufficient vegetable/seaweed consumption (p = 0.03), maintaining a normal weight (p = 0.03), and avoidance of smoking (p < 0.001). Awareness of hypertension is increasing, but hypertensive Korean patients demonstrate poor overall adherence to non pharmacological hypertension management guidelines. These findings suggest that well-planned education programs should be continued after hypertension is diagnosed. PMID- 27561007 TI - Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model. AB - Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells gamma-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about the damaging RIBE in an in vivo tumor model, which may have significant implication in improvement of cancer radiotherapy. PMID- 27561008 TI - Effect of IVIG Formulation on IgG Binding to Self- and Exo- Antigens In Vitro and In Vivo. AB - In relation to the recent trials of Intravenous Immunoglobulin (IVIG) in Alzheimer's Disease (AD) it was demonstrated that different IgG preparations contain varying amounts of natural anti-amyloid beta (Abeta) antibodies as measured by ELISA. We therefore investigated the relevance of ELISA data for measuring low-affinity antibodies, such as anti-Abeta. We analysed the binding of different commercial Immunoglobulin G (IgG) preparations to Abeta, actin and tetanus toxoid in different binding assays to further investigate the possible cause for observed differences in binding to Abeta and actin between different IgG preparations. We show that the differences of commercial IgG preparations in binding to Abeta and actin in ELISA assays are artefactual and only evident in in vitro binding assays. In functional assays and in vivo animal studies the different IVIG preparations exhibited very similar potency. ELISA data alone are not appropriate to analyse and rank the binding capacity of low-affinity antibodies to Abeta or other endogenous self-antigens contained in IgG preparations. Additional analytical methods should be adopted to complement ELISA data. PMID- 27561009 TI - Equality in Maternal and Newborn Health: Modelling Geographic Disparities in Utilisation of Care in Five East African Countries. AB - BACKGROUND: Geographic accessibility to health facilities represents a fundamental barrier to utilisation of maternal and newborn health (MNH) services, driving historically hidden spatial pockets of localized inequalities. Here, we examine utilisation of MNH care as an emergent property of accessibility, highlighting high-resolution spatial heterogeneity and sub-national inequalities in receiving care before, during, and after delivery throughout five East African countries. METHODS: We calculated a geographic inaccessibility score to the nearest health facility at 300 x 300 m using a dataset of 9,314 facilities throughout Burundi, Kenya, Rwanda, Tanzania and Uganda. Using Demographic and Health Surveys data, we utilised hierarchical mixed effects logistic regression to examine the odds of: 1) skilled birth attendance, 2) receiving 4+ antenatal care visits at time of delivery, and 3) receiving a postnatal health check-up within 48 hours of delivery. We applied model results onto the accessibility surface to visualise the probabilities of obtaining MNH care at both high resolution and sub-national levels after adjusting for live births in 2015. RESULTS: Across all outcomes, decreasing wealth and education levels were associated with lower odds of obtaining MNH care. Increasing geographic inaccessibility scores were associated with the strongest effect in lowering odds of obtaining care observed across outcomes, with the widest disparities observed among skilled birth attendance. Specifically, for each increase in the inaccessibility score to the nearest health facility, the odds of having skilled birth attendance at delivery was reduced by over 75% (0.24; CI: 0.19-0.3), while the odds of receiving antenatal care decreased by nearly 25% (0.74; CI: 0.61 0.89) and 40% for obtaining postnatal care (0.58; CI: 0.45-0.75). CONCLUSIONS: Overall, these results suggest decreasing accessibility to the nearest health facility significantly deterred utilisation of all maternal health care services. These results demonstrate how spatial approaches can inform policy efforts and promote evidence-based decision-making, and are particularly pertinent as the world shifts into the Sustainable Goals Development era, where sub-national applications will become increasingly useful in identifying and reducing persistent inequalities. PMID- 27561010 TI - Development of High Hydrostatic Pressure Applied in Pathogen Inactivation for Plasma. AB - High hydrostatic pressure has been used to inactivate pathogens in foods for decades. There is a great potential to adapt this technology to inactivate pathogens in plasma and derivatives. To better evaluate the potential of this method, pathogen inoculated plasma samples were pressurized under different pressure application modes and temperatures. The inactivation efficacy of pathogens and activities of plasma proteins were monitored after treatment. The CFUs of E.coli was examined as the indicator of the inactivation efficiency. The factor V and VIII were chosen as the indicator of the plasma function. Preliminary experiments identified optimized treatment conditions: 200-250MPa, with 5*1 minute multi-pulsed high pressure at near 0 degrees C (ice-water bath). Under this conditions, the inactivation efficacy of EMCV was >8.5log. The CFUs of E. coli were reduced by 7.5log, B. cereus were 8log. However, PPV and S. aureus cannot be inactivated efficiently. The activities of factor II, VII, IX, X, XI, XII, fibrinogen, IgG, IgM stayed over 95% compared to untreated. Factor V and VIII activity was maintained at 46-63% and 77-82%, respectively. PMID- 27561011 TI - Human energy expenditure, allocation, and interactions in natural temperate, hot, and cold environments. AB - OBJECTIVE: The aim of this research is to analyze how energy is allocated differently in temperate, hot, and cold environments among National Outdoor Leadership School students. METHOD: Basal metabolic rate, physical activity, thermoregulation, and the thermic effect of food were estimated to determine the total energy expenditure and energy allocation differences among a group of healthy, highly active adults (N = 59) participating in National Outdoor Leadership School courses in the western United States. Two of these courses took place in both hot and temperate climates (N = 22) and the other two in both temperate and cold climates (N = 28). Data from a pilot study (N = 6) in a temperate climate were also included. Each climate regime lasted for one month. RESULTS: Total energy expenditure values were statistically equivalent in temperate and hot climates (p = .97). However, subjects experienced significantly higher total energy expenditures in cold climates (p < .0001), expending an additional ~1550 kcal day-1 . There is a significant interaction between physical activity and thermoregulation, such that physical activity reduces thermoregulatory costs in cold climates, but increases it in hot climates. CONCLUSIONS: Dissection of the energy budget revealed that total energy expenditure is significantly higher in cold climates. This is due to a combination of high levels of physical activity and high thermoregulatory costs. High levels of physical activity may substantially lower the cost of thermoregulation in cold climates, and this interaction should be taken into account when estimating TEE. PMID- 27561013 TI - [The Hospital de Especialidades "Bernardo Sepulveda Gutierrez", and the generation of knowledge]. AB - The history of the Hospital de Especialidades "Bernardo Sepulveda Gutierrez," formerly called Hospital General del Centro Medico Nacional, has been marked by ups and downs, as well as by the development of cutting-edge medical knowledge. In this supplement we show a series of articles, whose authors belong in their entirety to that hospital. PMID- 27561012 TI - The Unusual Resistance of Avian Defensin AvBD7 to Proteolytic Enzymes Preserves Its Antibacterial Activity. AB - Defensins are frontline peptides of mucosal immunity in the animal kingdom, including birds. Their resistance to proteolysis and their ensuing ability to maintain antimicrobial potential remains questionable and was therefore investigated. We have shown by bottom-up mass spectrometry analysis of protein extracts that both avian beta-defensins AvBD2 and AvBD7 were ubiquitously distributed along the chicken gut. Cathepsin B was found by immunoblotting in jejunum, ileum, caecum, and caecal tonsils, while cathepsins K, L, and S were merely identified in caecal tonsils. Hydrolysis product of AvBD2 and AvBD7 incubated with a panel of proteases was analysed by RP-HPLC, mass spectrometry and antimicrobial assays. AvBD2 and AvBD7 were resistant to serine proteases and to cathepsins D and H. Conversely cysteine cathepsins B, K, L, and S degraded AvBD2 and abolished its antibacterial activity. Only cathepsin K cleaved AvBD7 and released Ile4-AvBD7, a N-terminal truncated natural peptidoform of AvBD7 that displayed antibacterial activity. Besides the 3-stranded antiparallel beta-sheet typical of beta-defensins, structural analysis of AvBD7 by two-dimensional NMR spectroscopy highlighted the restricted accessibility of the C-terminus embedded by the N-terminal region and gave a formal evidence of a salt bridge (Asp9-Arg12) that could account for proteolysis resistance. The differential susceptibility of avian defensins to proteolysis opens intriguing questions about a distinctive role in the mucosal immunity against pathogen invasion. PMID- 27561014 TI - [Clinical and biochemical characteristics of patients with morbid obesity at the time of hospital admission and one year after undergoing bariatric surgery]. AB - BACKGROUND: Three percent of Mexicans suffer from morbid obesity. Comorbidities associated to this condition diminish quality of life, increase mortality and health care costs. Despite bariatric surgery has specific indications and risks, it is the only treatment with effective long-term results. The aim of the study was to evaluate biochemical and clinical patient characteristics, both preoperatively and a year after they underwent bariatric surgery. METHODS: We carried out a quasi-experimental study that evaluates a sample of patients in the Clinica de Obesidad at Hospital de Especialidades (a third level hospital) between March 2011 and October 2015. RESULTS: A total of 150 patients were analyzed (60 % were women). Mean age was 41 +/- 9 years and mean body mass index (BMI) was 48 kg/m2 (42-53 kg/m2). Before surgery, type 2 diabetes mellitus (T2DM) was present in 31 %, hypertension in 60 % and 30 % of the patients were "metabolically healthy obese". A year after surgery, the percentage of excess body weight loss was 66 %, T2DM and hypertension remission was 70 % and 50 %, respectively. CONCLUSION: Bariatric surgery is an effective treatment to reduce excess weight. It improves biochemical, and clinical parameters in extreme obese patients. PMID- 27561015 TI - [Deep brain stimulation in Parkinson's disease. Preliminary outcomes]. AB - BACKGROUND: Parkinson's disease justifies the use of deep brain stimulation (DBS) in certain patients who suffer from this condition. We present mid-term and long term post-surgical outcomes in a cohort of 60 patients, who underwent DBS in the Hospital de Especialidades at Centro Medico Nacional Siglo XXI, in Mexico City. METHODS: Patients underwent conventional stereotactic surgery with FrameLink software (Medtronics Inc). This technique consisted in the presurgical evaluation, the placement of stereotactic frame, imaging studies, preoperative planning procedure, microrecording, macrostimulation, as well as the placement of electrodes and generators in two phases. The variables were included in a data platform for Excel management. It was also included a variety of measurement instruments for data comparison. As a standard measure, it was used the Unified Parkinson Disease Rating Scale (UPDRS) before the surgery and at 3, 12, and 36 months. RESULTS: 60 patients underwent surgery: 41 men and 19 women, with an average age of 56.5 years (39-70). There were good results in the majority of patients with preoperative UPDRS and at 3, 12 and 36 months of 79.57, 66.85, 65.29 and 58.75, respectively (p < 0.0001). There were complications in nine patients (15 %) and they were managed in a conservative manner. CONCLUSIONS: Postsurgical outcomes were from good to excellent in the majority of patients. Complications were minimal and conservatively managed. We propose the use of this procedure in a selected group of Parkinson's patients. PMID- 27561016 TI - [Surgical management of paraclinoid aneurysms]. AB - BACKGROUND: Paraclinoid aneurysms arise from C5 clinoid segment and C6 ophthalmic segment, within the internal carotid artery. Brain aneurysms have a frequency ranging from 5 to 11 %. A successful surgery requires knowledge of the anatomic region and the aneurysm. The objective was to show the surgical management of paraclinoid aneurysms. METHODS: From January 2009 to January 2015, we carried out a retrospective study in the Neurosurgery Department at Centro Medico Nacional Siglo XXI. We included 66 patients with the diagnosis of paraclinoid aneurysm. We obtained the clinical characteristics, evolution, complications, and outcomes from the clinical and radiological records. RESULTS: 61 patients (92.4 %) were female; 65 underwent neurosurgical clipping, and one underwent cerebral bypass surgery with exclusion of the aneurysm. Forty six patients presented subarachnoid hemorrhage due to aneurysmal rupture. By reason of their location, 35 paraclinoid aneurysms (53 %) were superior, 20 medial (30.3 %) and 4 inferior (6 %). Thirty three patients had small aneurysms, 23 large aneurysms, and 10 patients presented giant aneurysms. After surgery, 51 patients had good results, since they scored 4 and 5 in the Glasgow Outcome Score. Three patients presented amaurosis as a surgery-related complication. CONCLUSION: Microsurgical management is still the best treatment for these aneurysms, due to its ability to exclude them entirely; besides, is the best method to decompress the optic nerve. PMID- 27561017 TI - [Association between depression and hearing loss in patients with type 2 diabetes]. AB - BACKGROUND: The association between diabetes, hearing loss and depression is unknown, and needs to be understood clearly and precisely. Our objective was to estimate the association between depression and hearing loss in patients with type 2 diabetes. METHODS: Cross-sectional analytical study. Patients of 40 years or older with type 2 diabetes were studied. Anthropometric measurements and biochemical parameters were recorded. The Beck Depression Inventory and a pure tone audiometry were applied. Groups were compared with chi squared test and logistic regression for confounders. RESULTS: 150 patients were included (76 % women). Average age was 56 +/- 9.3 years, with 12.4 +/- 6.5 years of progression of diabetes, weight 67.4 +/- 11.6 kg; 31 % were obese; 25.5 % hypertensive (126.3 +/- 19.3 / 79.4 +/- 19.7 mm Hg) and 80.7 % had poor metabolic control (HbA1c >= 7 %). Of all the patients, 45.3 % presented hearing loss and 32.4 % depression. Diagnosis of depression in patients with hearing loss remained significant after adjusting for confounders (odds ratio [OR] = 2.3; 95 % confidence interval [CI] = 1.051-5.333, p = 0.037). Women had greater risk of depression, difference that remained significant (OR = 3.2; 95 % CI = 1.268-8.584, p = 0.014) after adjustment. CONCLUSIONS: Almost half of the patients with diabetes presented hearing loss and more than three times the risk of depression. Subjects with depression and diabetes presented more hearing loss (> 20 dB) than those without diabetes and/or without depression. PMID- 27561018 TI - [High-intensity chemotherapy versus palliative chemotherapy in patients over 60 years with acute myeloid leukemia]. AB - BACKGROUND: The use of high-intensity chemotherapy (HIC) for acute myeloid leukemia (AML) in the elderly is controversial. In the present study, it was assessed complete remission and overall survival of AML patients over 60 years treated with HIC or palliative chemotherapy. METHODS: Patients with ECOG <= 2 and adequate organic function received HIC with a base of cytarabine for five or seven days, and an anthracycline for three days. If patients achieved complete remission of leukemia, they received one or two cycles of consolidation with cytarabine. Palliative treatment consisted of supported measures and/or oral or intravenous low-dose chemotherapy. RESULTS: Seven patients treated with HIC achieved complete remission versus only one in the palliative group. Only one patient died during HIC treatment. Median survival for HIC-treated patients was 13.25 months, and only 3.35 months for patients treated with palliative therapy (p < 0.05). CONCLUSION: AML patients of 60 years or older, with good performance status (ECOG <= 2) and adequate organ function, may benefit from HIC treatment, with better survival, compared with palliative therapy. PMID- 27561019 TI - [Prognostic factors of morbimortality in patients with emphysematous pyelonephritis]. AB - BACKGROUND: Emphysematous pyelonephritis (EPN) is a severe infection of the urinary tract, caused by gas accumulation within the collecting system, the renal parenchyma, and/or the perirenal tissue. The cause of this infection is not known at all; however, it has been suggested that it is produced by the glucose fermentation provoked by enterobacteriaceae or anaerobic organisms. Our objective was to evaluate the predictors of morbidity and mortality in patients diagnosed with EPN. METHODS: It was carried out a historical cohort study of patients diagnosed with EPN in our hospital from March 2005 to December 2014. Patients with adverse outcome were identified. We defined adverse outcome as patients requiring stay in intensive care unit, who presented nephrectomy and/or who died. A multiple regression analysis was conducted to establish the relation of each clinical factor with the adverse outcome. RESULTS: 73 records were included for analysis, 48 were women (65.8 %) and 25 men. Diabetes, urolithiasis, E. coli infection and septic shock occurred in 68.5, 68.5, 63, and 15.1 %, respectively. We found that leukocytosis >=12 000 ul (OR 43.65, 95 % CI 2.36-805, p <0.001), thrombocytopenia <=120 000 ul (OR 363, 95 % 9.2-14208, p <0.0001), and Huang's radiological class 3 (OR 62, 95 % CI 4-964, p < 0.001) were factors significantly associated with adverse outcome. CONCLUSION: Thrombocytopenia, leukocytosis and Huang's radiological class 3 are associated with adverse outcome in patients with EPN. PMID- 27561020 TI - [Clinical features of patients with influenza-like illness who went to a third level center in the winter of 2013-2014]. AB - BACKGROUND: Between October 2013 and April 2014, the Centers for Disease Control and Prevention reported a high incidence of AH1N1 influenza cases. Not all suspicious cases of influenza are confirmed; however, all patients need treatment and generate additional costs to the institutions. Our objective was to describe the characteristics of the patients treated for influenza suspicion at Hospital de Especialidades in Centro Medico Nacional Siglo XXI during a new epidemic. METHODS: Cross-sectional study of all cases admitted at the Emergency Service (of the aforementioned hospital) for influenza-like illness, defined according to current guidelines. Based on these guidelines, we analyzed the risk factors that may have increased the severity of the infection. RESULTS: We registered a total of 109 patients with a mean age of 44 years, 78 % were under 60 years of age, 62 % were women, 75 % had at least one comorbidity, such as obesity (26 %) or hypertension (27 %). Only 65 patients had results from a confirmatory test, 33.8 % had positive diagnosis, and 21 % of them eventually died. CONCLUSIONS: The frequency of confirmed cases for influenza infection is low. The risk factors associated with complications and increased mortality are hypertension, leukocytosis and clinical presentation of severe acute respiratory syndrome. PMID- 27561021 TI - [Assessment of pulmonary complications in renal transplantation through the use of radiography]. AB - BACKGROUND: Lower respiratory tract infections are the most common complications in kidney transplant patients in the first six months and they are associated with high mortality. Other complications include pulmonary edema, pulmonary embolism, and pulmonary hemorrhage. The aim of this study was to evaluate pulmonary complications in kidney transplant patients by using chest radiography. METHODS: We analyzed a total of 516 chest X-rays of 150 patients who received a kidney transplant in 2014. Chest radiographs were performed in the preoperative and in the postoperative assessments, as well as within the next 48 hours after the surgery, and from 3 to 7, 8-15, 16-30, 31-90, 91-180 and 180 days. For the radiographic study of the lung parenchyma, chest was divided into four quadrants by assigning a value of 1 to each radiographic pattern: reticular, nodular alveolar occupation; lobar or segmental; atelectasis; and ground-glass. Lung parenchyma obtained a minimum value of 0 and a maximum value of 16 points. Also, we assessed variables such as gender, age, associated comorbidity, and type of renal transplantation. RESULTS: We obtained data from a total of 150 patients; 19 patients had pulmonary complications in the first 24 to 48 hours and 15 patients between 90 and 180 days after the kidney transplantation. The most frequent complications were acute pulmonary edema in early stage and infections in late stage. CONCLUSION: The prevalence of complications diagnosed by chest radiograph was low and it was observed more often in early and late stages. PMID- 27561022 TI - [Impact of frailty over the functional state of hospitalized elderly]. AB - BACKGROUND: Frailty in elderly results from impaired physiological reserve in multiple systems. Establishing if frail elderly inpatients develop more functional impairment at discharge, will allow the development of strategies for preventing or limiting the deterioration in this vulnerable group. METHODS: Prospective cohort in 133 elderly inpatients. At admission, frailty, functional status, comorbidity and comprehensive geriatric evaluation were determined. The main outcome was functional state at hospital discharge. RESULTS: 64 patients presented frailty (48.1%) and 69 did not present that state (51.9%), with a mean age of 73 and 68 years, respectively. Mean decrement in functional state at discharge was -8.06 % (IC 95 % -10.38 to -5.74), from 97.97 % to 89.91 % (p < 0.001) in patients who did not present frailty, and -21.18 % (IC 95 % -24.97 to 17.38), from 87.52 % to 66.34 % (p < 0.001) in frail patients. The difference between groups at discharge was -14.37 % (IC 95 % -16.80 to -11.94, p < 0.001) to the detriment of the frail. Frailty was associated with functional impairment in the univariated and multivariated analysis, beta -13.11 % (IC 95 % -17.45 to 8.78, p < 0.001) and beta -17.27 (IC 95 % -23.27 to -11.28, p < 0.001), respectively. In the final model, frailty (beta -14.73, IC 95 % -19.39 to -10.07, p < 0.001) and cognitive impairment (beta -8.19, IC 95 % -15.28 to -1.10, p = 0.024) predict functional decrement. CONCLUSION: Frailty independently predicts functional impairment at hospital discharge. PMID- 27561023 TI - [Clinical and demographic characteristics of patients with multiple sclerosis]. AB - BACKGROUND: Multiple sclerosis (MS) is a disease whose physiopathogenesis shows a complex interaction of genetic and environmental factors. Given that those factors have not been documented in our country, we describe the clinical and demographic characteristics from a sample of patients with MS. METHODS: We carried out an observational, descriptive, cross-sectional, and retrolective study in a Center for Demyelinating Diseases. We took the information from the clinical records of a sample of patients with multiple sclerosis, who arrived to the center from April 2014 to July 2015. RESULTS: We obtained data from 313 patients, out of which 65.5 % were women. Mean age was 41 years (SD 11.22). Minimum age of diagnosis was 12 years and maximum, 66 years; mean age of diagnosis was 32 years (SD 9.72). With regards to clinical variables, 3.4 % presented radiologically isolated syndrome (RIS), 82 % relapsing-remitting MS (RRMS), 13.9 % secondary-progressive MS (SPMS), and 0.8 % primary-progressive MS (PPMS). Of all the patients, 10 % had first or second degree relatives with diagnosis of this disease; 16 % had foreign ancestors; 27 % were smokers. Treatment consisted of glatiramer acetate, 28 %; intramuscular interferon beta 1a, 18 %; subcutaneous interferon beta 1a, 16 %; subcutaneous interferon beta 1b, 30 %; fingolimod, 3 %; and others, 5 %. CONCLUSIONS: Clinical and demographic characteristics are similar to those reported in international literature. More studies would be needed to typify Mexican population with MS. PMID- 27561024 TI - [Association of inflammatory cytokines with bone turnover markers in type 1 diabetes]. AB - BACKGROUND: Diabetes mellitus (DM) adversely affects the skeleton and the physiological mechanisms implicated have not been explained sufficiently. Thus, the objective was to identify inflammatory cytokines (IL-1, IL-6 and TNF-alpha) in patients with T1DM and their association with markers of bone formation (sPINP) and markers of bone resorption (sCTX). METHODS: We studied 62 patients of 18 years of age or more with T1DM. We determined the values of HbA1c, vitamin D, inflammatory cytokines, as well as those of markers of bone formation and of markers of bone resorption. RESULTS: 49 patients were female with a mean age of 33.5 years. We found values of HbA1c > 7.5 in 83 %, vitamin D of 16 ng/mL. In patients with HbA1c >7.5 we found a positive correlation between TNF-alpha and sCTX (r = 0.43, p = 0.05), IL-6 and sCTX (r = 0.48, p = 0.037). With a model of simple linear regression between IL-6 and sCTX, it was found a beta coefficient of 23.8 with a p = 0.030 (95 % CI = 2-45.6), ie.: for every unit increase in IL-6 there is a sCTX increase of 23.8 pg/mL. CONCLUSIONS: We found a positive association between TNF-alpha and IL-6 with the marker of bone resorption (sCTX) in the group of patients with HbA1c > 7.5. The loss of metabolic control was associated with TNF-alpha and IL-6. PMID- 27561025 TI - [Predictors of extubation failure in neurosurgical patients]. AB - BACKGROUND: The information regarding the factors that affect the success of extubation in neurosurgical patients is limited; thus, it is necessary to determine the prevalence, and the associated factors, of extubation failure in neurosurgical patients. METHODS: It was performed a prospective, longitudinal, observational and comparative study in neurosurgical patients with criteria for extubation. In those who the number of endotracheal aspirations had failed 24 hours before extubation, it was analyzed the presence of cough reflex, length of stay and mechanical ventilation days. RESULTS: 70 patients were included in the study, of whom 11.4 % patients failed extubation and the associated factors were performing 6 events or more of endotracheal tube suction 24 hours prior to weaning (relative risk [RR] = 1.88, 95 % confidence interval [CI] = 1.14-3.09, p 0.01), 7 days of mechanical ventilation (RR = 1.31, 95 % CI = 1.08-1.57, p 0.005) and a length of hospital stay of 7.5 days (RR = 1.24, 95 % CI = 1.05-1.47, p 0.01). CONCLUSIONS: Performing 6 or more endotracheal tube suction events during the 24 hours before extubation is a risk factor for extubation failure in neurosurgical patients. PMID- 27561026 TI - [Vitamin D deficiency associated with insulin resistance in medical residents]. AB - BACKGROUND: Several studies have reported a correlation between vitamin D deficiency and insulin resistance; however, other clinical trials show that vitamin D supplementation do not normalize glucose and insulin levels. We designed a study to show if there is a correlation between serum vitamin D and the homeostatic model assessment 2 (HOMA 2). METHODS: It was designed a cross sectional, descriptive, and analytical study, which included medical residents. They answered a questionnaire to record the time of sun exposure. We took anthropometric measurements, such as weight, height, and waist circumference, as well as some serum levels: serum vitamin D, serum insulin, fasting blood glucose, triglycerides and high-density lipoprotein-cholesterol. The correlation between serum vitamin D and HOMA 2 was determined by the correlation of Pearson; it was considered significant a p < 0.05. RESULTS: The decreased serum vitamin D levels did not correlate with high concentrations of HOMA 2 (r = -0.11, p = 0.34). A negative correlation between vitamin D levels and index size waist was observed (r = -0.27, p = 0.025). HOMA 2 was positively correlated with waist size index (r = 0.23, p = 0.05) and triglycerides (r = 0.61, p = 0.01) and negatively with high density lipoprotein-cholesterol (r = -0.26, p = 0.02). CONCLUSIONS: We couldn't show the correlation between vitamin D deficiency and insulin resistance. PMID- 27561027 TI - [Frailty syndrome in patients with rheumatoid arthritis]. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic disabling disease, which leads to joint destruction and functional limitations. It diminishes health-related quality of life (HRQoL) and life expectancy. Frailty is a chronic inflammatory process related to aging that causes disability and affects HRQoL. The presence of comorbidity and polypharmacy are both related to RA severity. The aim of this study was to assess the prevalence of frailty and comorbidities in patients with RA. METHODS: Based on the American College of Rheumatology (ACR) criteria, we studied patients with RA that were seen at the outpatient clinic of the Rheumatology Department of a third level hospital. We applied the frailty criteria according to the Cardiovascular Health Study. We registered demographic data along with comorbidities and polypharmacy, using a cross-sectional, observational, and descriptive study design. RESULTS: Five hundred consecutive RA patients were included, 453 (90.6 %) were female.Mean age was 51.3 years and mean disease duration was 13.2 years; 23.4 % met frailty criteria. Mean number of comorbidities was 1.59, with systemic hypertension and obesity as the most frequent ones (25.2 % and 18.2 %, respectively). Polypharmacy was found in 99.6 % and 69.6 % received more than five drugs simultaneously. CONCLUSIONS: Prevalence of frailty in this study was unexpectedly high and so were comorbidities and multiple drug usage. Clinicians should make an early detection of signs of frailty and comorbidity in RA patients. PMID- 27561028 TI - [Excessive spending by misuse of clinical laboratory]. AB - Seventy five percent or more of a diagnosis comes from a proper medical history along with an excellent physical examination. This leaves to the clinical laboratory the function of supporting the findings, determining prognosis, classifying the diseases, monitoring the diseases and, in the minimum of cases, establishing the diagnosis. In recent years there has been a global phenomenon in which the allocation of resources to health care has grown in an excessive way; the Instituto Mexicano del Seguro Social is not an exception with an increase of 29 % from 2009 to 2011; therefore, it is necessary to set containment and reduction without compromising the quality of patient care. PMID- 27561029 TI - SWEF Proteins Distinctly Control Maintenance and Differentiation of Hematopoietic Stem Cells. AB - SWAP-70 and DEF6, two proteins that feature similar domain and motif arrangements, are mainly known for their functions in differentiated hematopoietic cells. Both proteins interact with and regulate RhoGTPases and F actin dynamics, yet their role in hematopoietic stem and precursor cells (HSPCs) remained unexplored. Here, the role of the SWEF proteins SWAP-70 and DEF6 in HSPCs was examined. Both SWEF proteins are expressed in HSCs. HSCs and different precursor populations were analyzed in mice deficient for SWAP-70, DEF6, SWAP-70 and DEF6 (double knockout, DKO), and wild-type controls. HSPCs isolated from these strains were used for competitive adoptive transfer into irradiated wild type mice. Reconstitution of the myeloid and lymphoid lineages in the recipient mice was determined. The numbers of HSPCs in the bone marrow of Swap-70-/- and Swap-70-/-Def6-/- mice were >3-fold increased. When transplanted into lethally irradiated wild-type recipients, the reconstitution potential of Swap-70-/- HSPCs was intrinsically impaired in competing with wild-type HSPCs for contribution to hematopoiesis. Def6-/- HSPCs show wild type-like reconstitution potential under the same transplantation conditions. DKO HSPCs reconstituted to only 25% of wild type levels, indicating a partial rescue by DEF6 deficiency in the Swap-70-/- background. Our study reveals the two SWEF proteins as important contributors to HSPC biology. Despite their similarity these two proteins regulate HSC/progenitor homeostasis, self-renewal, lineage contributions and repopulation in a distinct and mostly antagonistic manner. PMID- 27561030 TI - A fluorogenic screening platform enables directed evolution of an alkyne biosynthetic tool. AB - Directed evolution was used to improve the activity of JamB, a membrane-bound bifunctional desaturase/acetylenase. To quickly assess the protein engineering outcomes, we developed a new platform for quantifying extracellular alkyne-tagged metabolites through a fluorogenic click reaction. Random mutagenesis yielded the best JamB variant with ~20-fold increased activity in E. coli. PMID- 27561031 TI - Prevalence of celiac disease in first-degree relative of children in Sistan and Baluchestan province (Iran). AB - OBJECTIVE: To determine the prevalence of elevated antibodies and histological changes of celiac disease (CD) on intestinal biopsies among first-degree relatives (FDR) of Iranian children with known CD and to describe the characteristics of the affected FDR. METHOD: The FDR of 119 patients with CD in Iran were tested for tissue transglutaminase (TTG) and immunoglobulin A (IgA) levels. Upper endoscopy and duodenal biopsy were recommended to those with elevated TTG-IgA antibodies. The characteristics and clinical features of all CD patients were recorded. RESULTS: Altogether 480 FDR (52.7% females) participated in the study, of whom 63 had an elevated TTG-IgA and 44 consented to undergo endoscopy with biopsies. Histology revealed Marsh 0 in six, Marsh I in seven, Marsh II in four and Marsh III in 27. Most of those with Marsh II or III changes were siblings (26/31). The prevalence of TTG-IgA positivity among FDR was 13.1% and for biopsy-confirmed CD (Marsh II and III) it was 6.5%. Most FDR with CD had symptoms, with the most common being abdominal pain (45.0%), followed by musculoskeletal pain (35.5%) and constipation (25.8%). FDR with Marsh III changes had significantly higher levels of TTG-IgA. CONCLUSIONS: The prevalence of CD in FDR in Iran is much higher compared with the general population (6.5% vs 0.5 0.6%). Testing should be considered for all FDR of Iranian patients with known CD and in particular in symptomatic cases. PMID- 27561076 TI - Mechanical, tribological and biological properties of novel 45S5 Bioglass(r) composites reinforced with in situ reduced graphene oxide. AB - 45S5 Bioglass(r) (45S5) is one of the most widely used biomaterials in ceramic based bone graft substitutes by virtue of its excellent biocompatibility and bioactivity. However, the fracture toughness and wear resistance of 45S5 have to be improved to extend its applications in load bearing orthopedic implants. The current study reports the first use of graphene nanoplatelet (GNP) to enhance the fracture toughness and wear resistance of 45S5. Composite powders with four different loadings of graphene oxide (GO), i.e. 0, 0.1, 0.5 and 1wt%, were sintered by spark plasma sintering (SPS) at a relatively low temperature of 550 degrees C, during which in situ thermal reduction of GO took place. It was found that by adding 0.5wt% GO to the 45S5 powder, the fracture toughness of the sintered pellets was increased by 130.2% while friction coefficient and specific wear rate were decreased by 21.3% and 62.0%, respectively. Furthermore, the viability of MG63 cells grown on the GNP-incorporated pellets was comparably high to that of the cells grown on the pure 45S5 pellets. As compared with the pure 45S5 leachates, the media conditioned by the GNP/45S5 pellets fabricated from the composite powder with 1wt% GO could enhance both the proliferation and viability of MG63 cells. It is thus envisioned that the GNP-reinforced 45S5 is a highly promising material for fabricating mechanically strong and biocompatible load bearing bone implants. PMID- 27561077 TI - miR-570 interacts with mitochondrial ATPase subunit g (ATP5L) encoding mRNA in stored platelets. AB - Loss of platelet quality during ex vivo storage is a major concern in the transfusion medicine field and it has been known that platelet mitochondrial dysfunction is associated with storage time. In the last decade, small noncoding RNAs also known as microRNAs (miRNAs) have been reported to regulate key cellular processes through their target sequence interactions with selected mRNAs. In this study, we focused on understanding the mechanisms of platelet mitochondrial dysfunction during storage through miRNA regulation of mRNAs. RNA was isolated from day 0, day 5, and day 9 of stored human leukocyte-depleted platelets and subjected to differential miRNA and mRNA profiling. The miRNA profiling identified several miRNAs at low levels including a set of 12 different miR-548 family members (miR-548a-3p, miR-548aa, miR-548x, miR-548ac, miR-548c-3p, miR 603, miR-548aj, miR-548ae, miR-548z, miR-548u, miR-548al, and miR-570-3p). The mRNA profiling identified, among many, the mitochondrial ATP synthase subunit g (ATP5L) mRNA at high levels during storage. Target Scan algorithm for potential targets of miR-570-3p also identified ATP5L as one of its targets. We further identified two target sites for miR-570-3p in the 3' untranslated region (3'UTR) of ATP5L mRNA. While ATP5L is a subunit of F0ATPase complex, its function is not established yet. Overexpression of miR-570-3p in platelets resulted in reduced levels of ATP5L mRNA and concomitant ATP loss. These experimental results provide first-time insights into the miRNA-mRNA interactions underlying mitochondrial dysfunction in ex vivo stored platelets and warrants further investigation. PMID- 27561079 TI - MicroRNAs role as potential biomarkers and key regulators in melanoma. AB - Malignant melanoma (MM) is a highly aggressive skin cancer with high incidence worldwide. It originates from melanocytes and is characterized by invasion, early metastasis and despite the use of new drugs it is still characterized by high mortality. Since an early diagnosis determines a better prognosis, it is important to explore novel prognostic markers in the management of patients with MM. microRNAs (miRNAs) are small (~22 nucleotides) single-stranded non-coding RNAs that negatively regulate the expression of more than 60% of human genes.miRNAs alterations are involved in several cancers, including MM, where a differential expression for some of them has been reported between healthy controls and MM patients. Moreover, since miRNAs are stable and easily detectable in body fluids, they might be considered as robust candidate biomarkers useful to identify risk of MM, to diagnose an early lesion and/or an early metastatic disease. This review highlights the importance of miRNAs as risk factors, prognostic factors and their role as molecular regulator in the development and progression of MM. (c) 2016 Wiley Periodicals, Inc. PMID- 27561078 TI - Black Phosphorus Based Photocathodes in Wideband Bifacial Dye-Sensitized Solar Cells. AB - Ultrasmall black phosphorus quantum dots (BPQDs) serve as the near-infrared light absorber and charge transfer layer in the photocathode of a bifacial n-type dye sensitized solar cell. Wideband light absorption and ~20% enhancement in the light-to-electron efficiency are accomplished due to the fast carrier transfer and complementary light absorption by the BPQDs demonstrating that BP has large potential in photovoltaics. PMID- 27561080 TI - The effect of upper eyelid blepharoplasty on eyelid and brow position. AB - This article evaluates the effect of upper eyelid blepharoplasty on eyelid margin position and brow height. This study is a retrospective analysis of patients who underwent upper eyelid blepharoplasty without concurrent blepharoptosis repair or brow surgery. The medical records of the participants were retrospectively reviewed and an established image analysis software was used to quantify the upper margin reflex distance (MRD1) as well as brow height using high quality standardized clinical photographs. A total of 19 patients (38 eyelids and brows) met the inclusion criteria. The mean preoperative MRD1 was 2.8 mm, and the mean post-operative MRD1 was 3.5 mm, revealing an increase of MRD1 from upper blepharoplasty alone of 0.7 mm (p = 0.0001). The mean preoperative brow position was 17.5 mm above the pupil, and the mean post-operative position was 17.4 mm, for an average change of position of -0.2 mm (p = 0.39) following upper eyelid blepharoplasty. Upper eyelid blepharoplasty without ptosis surgery results in a statistically significant increase in MRD1. Brow position does not demonstrate a statistically significant change in patients who undergo upper eyelid blepharoplasty for simple dermatochalasis. PMID- 27561081 TI - National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2015. AB - The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive vaccines to prevent diseases, including human papillomavirus (HPV)-associated cancers, pertussis, and meningococcal disease (1). To assess vaccination coverage among adolescents in the United States, CDC analyzed data collected regarding 21,875 adolescents through the 2015 National Immunization Survey-Teen (NIS-Teen).* During 2014-2015, coverage among adolescents aged 13-17 years increased for each HPV vaccine dose among males, including >=1 HPV vaccine dose (from 41.7% to 49.8%), and increased modestly for >=1 HPV vaccine dose among females (from 60.0% to 62.8%) and >=1 quadrivalent meningococcal conjugate vaccine (MenACWY) dose (from 79.3% to 81.3%). Coverage with >=1 HPV vaccine dose was higher among adolescents living in households below the poverty level, compared with adolescents in households at or above the poverty level.(?) HPV vaccination coverage (>=1, >=2, or >=3 doses) increased in 28 states/local areas among males and in seven states among females. Despite limited progress, HPV vaccination coverage remained lower than MenACWY and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) coverage, indicating continued missed opportunities for HPV-associated cancer prevention. PMID- 27561082 TI - Correction: HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days-Implications for HIV Remission. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005000.][This corrects the article DOI: 10.1371/journal.ppat.1005740.][This corrects the article DOI: 10.1371/journal.ppat.1005679.]. PMID- 27561083 TI - Issues in developing multivariable molecular signatures for guiding clinical care decisions. AB - Omics technologies that generate a large amount of molecular data characterizing biospecimens have the potential to provide information about patients' disease characteristics above and beyond standard clinical features. By combining information from a large number of features into a multivariable model, called a biomarker signature, there is the opportunity to identify distinct subgroups of patients for whom treatment decisions can be personalized. The key challenge is to derive a signature with good performance and appropriately characterize its performance. We summarize the key statistical issues and methods for developing and validating biomarker signatures, using examples from the literature for illustration. PMID- 27561084 TI - Exploring the importance of case-level clinical information for variant interpretation. PMID- 27561085 TI - Long-term follow-up in newborn screening: the role of collaboration. PMID- 27561086 TI - Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results. AB - PURPOSE: Eliciting and understanding patient and research participant preferences regarding return of secondary test results are key aspects of genomic medicine. A valid instrument should be easily understood without extensive pretest counseling while still faithfully eliciting patients' preferences. METHODS: We conducted focus groups with 110 adults to understand patient perspectives on secondary genomic findings and the role that preferences should play. We then developed and refined a draft instrument and used it to elicit preferences from parents participating in a genomic sequencing study in children with intellectual disabilities. RESULTS: Patients preferred filtering of secondary genomic results to avoid information overload and to avoid learning what the future holds, among other reasons. Patients preferred to make autonomous choices about which categories of results to receive and to have their choices applied automatically before results are returned to them and their clinicians. The Preferences Instrument for Genomic Secondary Results (PIGSR) is designed to be completed by patients or research participants without assistance and to guide bioinformatic analysis of genomic raw data. Most participants wanted to receive all secondary results, but a significant minority indicated other preferences. CONCLUSIONS: Our novel instrument-PIGSR-should be useful in a wide variety of clinical and research settings.Genet Med 19 3, 337-344. PMID- 27561087 TI - Current Knowledge about Oxysterols: A Review. AB - For years food consumers have been warned that a cholesterol-rich diet may result in atherosclerosis. It is also well known that consumption of large amounts of phytosterols decreases concentration of low-density lipoproteins (LDLs) in blood (LDLs are regarded a key risk factor in development of cardiovascular diseases). However, no scientific evidence has unambiguously proved any direct connection between amount of consumed cholesterol and LDL level in blood. On the other hand, concentration of cholesterol oxidation products, oxysterols, seems to be indeed relevant; for example, they significantly impact appearance of atherosclerotic lesions (plaques). Phytosterols (like sitosterol or campasterol) decrease LDL level in blood, but on the other hand products of their oxidation are toxic. Therefore, it is worth to know influence of phytosterols on living organisms, processes which lead to their formation, and their levels in popular foodstuffs. This paper is an attempt to review literature data on the above aspects, as well as on impact on living organisms of oxidation products of popular sterols. PMID- 27561088 TI - Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma. AB - We report an interesting clinical case of a patient carrying a specific BRCA2 germline variant affected by bone and hepatic metastases from a high grade uterine stromal sarcoma who obtained a complete metabolic response after only 3 cycles of trabectedin treatment (1.5 mg/m2 given intravenously over 24 hours every 21 days). Molecular investigations linked this outstanding positive pharmacological response with the loss of heterozygosity (LOH) of the mutated BRCA2 gene. These data support the hypothesis that the response to trabectedin may be positively conditioned by the different DNA repair defects present in the neoplasm and that BRCAness tumor genotype is important in determining the efficacy of trabectedin-based chemotherapy. PMID- 27561089 TI - Correction: Social Complexification and Pig (Sus scrofa) Husbandry in Ancient China: A Combined Geometric Morphometric and Isotopic Approach. AB - [This corrects the article DOI: 10.1371/journal.pone.0158523.]. PMID- 27561090 TI - Comparison of neuropsychological test scores of high school athletes in high and low contact sports: A replication study. AB - This replication study re-examined the neuropsychological effects of participation in high and low contact youth sports. Modeled after a recently published investigation, two contact sport groups of participants ages 12 to 18 were formed based on the rate of concussion in their respective sport, with the assumption that more head impacts and neuropsychological effects occur in high contact sports that have a greater number of reported concussions as compared with low contact sports. The preseason baseline ImPACT neuropsychological test scores and symptom scores of non-concussed youth athletes in a High Contact Sport (football, n = 139) and a Low Contact Sport (basketball, baseball, soccer, wrestling, volleyball, paddling, and cheerleading, n = 57) were compared. The results revealed significantly poorer ImPACT test performances in visual motor speed and reaction time among high contact sport athletes compared to low contact sport athletes. No differences were found between the two groups in Verbal Memory, Visual Memory, and Total Symptom. These findings were identical to a recent study in which nonconcussed youth athletes in a high contact sport, that is, football, exhibited poorer neuropsychological test performance than their peers in low contact sports, that is, basketball, baseball, soccer, wrestling, and judo. This research replication verified the results of the prior study, and raises concerns that youth athletes exposed to repetitive head trauma may be at risk for lowered neuropsychological functioning, even without a reported concussive event. PMID- 27561092 TI - New Cassane Diterpenes from the seeds of Caesalpinia decapetala. PMID- 27561091 TI - NTD and NCD Co-morbidities: The Example of Dengue Fever. PMID- 27561094 TI - Optimal Interval between Ultrasound Scans for the Detection of Complications in Monochorionic Twins. AB - INTRODUCTION: Monochorionic-diamniotic (MCDA) twin pregnancies are high risk, due to twin-to-twin transfusion syndrome (TTTS), twin anaemia polycythaemia sequence (TAPS) and intrauterine growth restriction (IUGR). There is limited evidence to guide ultrasound surveillance protocols. Using a retrospective cohort, we aimed to provide insight into the optimal interval of ultrasound surveillance. METHODS: Retrospective cohort of women with MCDA pregnancies who received antenatal care at Monash Medical Centre (January 2011-October 2014). We reviewed all ultrasounds from >=15 weeks' gestation and collected perinatal outcomes. RESULTS: A total of 162 women with MCDA pregnancies attended our care. Six women were excluded due to late referral. Of the remaining 156, 55% were uncomplicated. TTTS, TAPS, IUGR and fetal demise in utero occurred in 9%, 1%, 31% and 2%, respectively. Median interval between the last ultrasound and TTTS diagnosis was 3.1 weeks (IQR 0.8 5.8). There was a trend towards a longer interval for cases with advanced TTTS compared to early TTTS. Interval between ultrasound scans was longer in cases with unexplained fetal demise in utero and advanced TTTS than early TTTS [3.4 weeks (IQR 2.0-6.9) vs. 0.9 weeks (IQR 0.4-3.7); p < 0.05]. DISCUSSION: Our observations support current recommendations for fortnightly ultrasound surveillance in MCDA pregnancies from 16 weeks' gestation and suggest that longer intervals may be associated with poorer outcomes. PMID- 27561093 TI - Association of Matrix Metalloproteinases -7, -8 and -9 and TIMP -1 with Disease Severity in Acute Pancreatitis. A Cohort Study. AB - OBJECTIVES: Several biomarkers for early detection of severe acute pancreatitis (SAP) have been presented. Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are released early in inflammation. We aimed to assess levels of MMP-7, -8, -9 and TIMP-1 in acute pancreatitis (AP) and explore their ability to detect disease severity. Our second aim was to find an association between MMPs, TIMP and creatinine. METHODS: We collected plasma samples for MMP-7, -8, -9 and TIMP-1 analyses from 176 patients presenting within 96 h from onset of acute pancreatitis (AP) symptoms. We used samples from 32 control subjects as comparison. The revised Atlanta Classification was utilised to assess severity of disease. Receiver operating characteristic curve analysis and Spearman's Rho-test were utilised for statistical calculations. RESULTS: Compared with controls, patients showed higher levels of all studied markers. MMP-8 was higher in moderately severe AP than in mild AP (p = 0.005) and MMP-8, -9 and TIMP-1 were higher in severe than in mild AP (p<0.001, p = 0.005 and p = 0.019). MMP-8 detected SAP with an AUC of 0.939 [95% CI 0.894-0.984], LR+ 9.03 [5.30-15.39]. MMP-8, -9 and TIMP-1 failed to discern moderately severe AP from SAP. MMP-7 was not different between patient groups. MMP-7 and TIMP-1 correlated weakly with creatinine (Rho = 0.221 and 0.243). MMP-8 might be a useful biomarker in early detection of SAP. PMID- 27561095 TI - Anticonvulsant activity of the antidepressant drug, tianeptine, against pentylenetetrazole-induced seizures mitigates cognitive impairment in rats. AB - Treatment of depression, a common comorbidity in patients with epilepsy, is restricted as certain antidepressants are considered to be proconvulsants. In contrast, anticonvulsant effects have been reported with some antidepressants. In the present study, the effect of tianeptine, an antidepressant, was evaluated against pentylenetetrazole (PTZ)-induced seizures, cognitive impairment and oxidative stress in rats. Tianeptine was administered in three doses (20, 40 and 80 mg/kg) 30 min before PTZ (60 mg/kg, intraperitoneally). MK801, an N-methyl-D aspartate antagonist, and naloxone, an opioid receptor antagonist, were administered with tianeptine to evaluate the involvement of N-methyl-D-aspartate and opioid receptors, respectively. Morris water maze, elevated plus maze and passive avoidance tests were performed for behavioural assessment. Brain malondialdehyde and reduced glutathione levels were estimated as markers of oxidative stress. Tianeptine showed dose-dependent protection against PTZ seizures. Coadministration of tianeptine with MK801 potentiated the anticonvulsant effect of tianeptine. The protective effect of tianeptine against PTZ seizures was mitigated when tianeptine was administered with naloxone. Impairment of learning and memory by PTZ was prevented by tianeptine. Tianeptine also attenuated the seizure-induced increased oxidative stress. Thus, tianeptine showed an anticonvulsant effect along with amelioration of seizure-induced cognitive impairment and oxidative stress. Hence, tianeptine could be a useful drug in epileptic patients with depression, with the advantage of having both antidepressant and antiepileptic effects. PMID- 27561096 TI - Sulfo-SMCC Prevents Annealing of Taxol-Stabilized Microtubules In Vitro. AB - Microtubule structure and functions have been widely studied in vitro and in cells. Research has shown that cysteines on tubulin play a crucial role in the polymerization of microtubules. Here, we show that blocking sulfhydryl groups of cysteines in taxol-stabilized polymerized microtubules with a commonly used chemical crosslinker prevents temporal end-to-end annealing of microtubules in vitro. This can dramatically affect the length distribution of the microtubules. The crosslinker sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, sulfo-SMCC, consists of a maleimide and an N-hydroxysuccinimide ester group to bind to sulfhydryl groups and primary amines, respectively. Interestingly, addition of a maleimide dye alone does not show the same interference with annealing in stabilized microtubules. This study shows that the sulfhydryl groups of cysteines of tubulin that are vital for the polymerization are also important for the subsequent annealing of microtubules. PMID- 27561097 TI - 5-Formylcytosine Could Be a Semipermanent Base in Specific Genome Sites. AB - 5-Formyl-2'-deoxycytosine (fdC) is a recently discovered epigenetic base in the genome of stem cells, with yet unknown functions. Sequencing data show that the base is enriched in CpG islands of promoters and hence likely involved in the regulation of transcription during cellular differentiation. fdC is known to be recognized and excised by the enzyme thymine-DNA-glycosylase (Tdg). As such, fdC is believed to function as an intermediate during active demethylation. In order to understand the function of the new epigenetic base fdC, it is important to analyze its formation and removal at defined genomic sites. Here, we report a new method that combines sequence-specific chemical derivatization of fdC with droplet digital PCR that enables such analysis. We show initial data, indicating that the repair protein Tdg removes only 50 % of the fdCs at a given genomic site, arguing that fdC is a semipermanent base. PMID- 27561098 TI - Advances in dopamine receptor agonists for the treatment of Parkinson's disease. AB - INTRODUCTION: Dopamine agonists (DA) are a class of agents which directly stimulate dopamine receptors mimicking the endogenous neurotransmitter dopamine. At first used as adjunctive therapy in the advanced phases of the disease, over the years a significant role was found for DA monotherapy as a first approach in the initial stage of Parkinson's disease (PD). Several reviews have already reported efficacy and safety of DA in PD and differences between DA and levodopa. Therefore the objective of this review is to gather recent updates in DA therapy. A thorough knowledge of recent literature evidences, would help clinician in the management of treatment with DA. AREAS COVERED: Our review investigates recent updates on DA therapy, the role of these compounds in controlling non-motor symptoms (NMS) as well as new formulations under clinical evaluation and newly emerged post-marketing safety considerations. A literature search has been performed using Medline and reviewing the bibliographies of selected articles. EXPERT OPINION: DA represents a very important option in the treatment of PD, even though there are still some criticisms and unmet needs. A better knowledge of dopamine receptors could lead to identification of new compounds able to better balance clinical efficacy and side effects. PMID- 27561099 TI - Nomograms for Predicting the Prognostic Value of Pre-Therapeutic CA15-3 and CEA Serum Levels in TNBC Patients. AB - Previous studies have indicated that carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are both independent prognostic factors in breast cancer. However, the utility of CEA and CA15-3 levels as conventional cancer biomarkers in patients with triple-negative breast cancer (TNBC) remains controversial. The current study was performed to explore the predictive value of pre-therapeutic serum CEA and CA15-3 levels, and nomograms were developed including these serum cancer biomarkers to improve the prognostic evaluation of TNBC patients. Pre-therapeutic CA15-3 and CEA concentrations were measured in 247 patients with stage I-IV TNBC. Kaplan-Meier analysis showed that TNBC patients with high levels of both CEA and CA15-3 had shorter overall survival (OS) and disease-free survival (DFS) rates than those in the low-level groups (p<0.05). Multivariate analysis suggested that pre-therapeutic CA15-3 and CEA levels are independent predictive elements for OS (p = 0.022 and p = 0.040, respectively) and DFS (p = 0.023 and p = 0.028, respectively). In addition, novel nomograms were established and validated to provide personal forecasts of OS and DFS for patients with TNBC. These novel nomograms may help physicians to select the optimal treatment plans to ensure the best outcomes for TNBC patients. PMID- 27561100 TI - Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo. AB - Long-term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low-intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE-LTICv cells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk-pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted. PMID- 27561101 TI - Differences in Ocular Blood Flow Between People of African and European Descent With Healthy Eyes. AB - PURPOSE: To investigate differences in ocular blood flow between people of African descent (AD) and European descent (ED) with healthy eyes. MATERIALS AND METHODS: Retrobulbar and retinal capillary blood flow was assessed in 1 eye of 58 participants (24 AD, 34 ED) with healthy eyes with systemic blood pressure lower than 140/90. Retrobulbar blood flow was measured in the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA) and temporal posterior ciliary artery (TPCA). Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were assessed. Retinal capillary blood flow was assessed using mean retinal flow and avascular space defined as the percent of area measured with no blood flow. Groups were compared using t tests and Pearson correlations were compared using Fisher r-to-z transformation. RESULTS: Compared with people of ED, people of AD had significantly lower EDV in the NPCA (P=0.01), and higher RI in the CRA (P=0.04) and TPCA (P=0.01). No significant differences were observed in mean retinal capillary flow or avascular area. In the CRA, a significant negative correlation was observed between pattern standard deviation and peak systolic velocity (P=0.02) in the AD group and this correlation was significantly different from that observed in the ED group (P=0.01). A significant correlation was also observed between pattern standard deviation and EDV (0.04) in the AD group. CONCLUSIONS: This study suggests that retrobulbar blood flow is lower in healthy eyes in persons of AD compared with ED. This may provide a mechanism through which people of AD are at increased risk for ophthalmic diseases such as glaucoma. PMID- 27561103 TI - Recent Developments in Melanoma Therapy. PMID- 27561102 TI - Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open angle Glaucoma Patients of African Descent Compared With Patients of European Descent. AB - PURPOSE: To investigate the relationship of changes in ocular blood flow with optic nerve head (ONH) and retinal morphology in open-angle glaucoma (OAG) patients of African versus European descent (ED) over 4 years. MATERIALS AND METHODS: In this study, 112 patients with OAG were examined at baseline, 79 [59 ED, 20 African descent (AD)] of which were followed for 4 years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured by color Doppler imaging. Retinal structural changes were examined with optical coherence tomography and Heidelberg retinal tomography-III. Mixed-model analysis of covariance was used to test for the significance of change from baseline to 4-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations. RESULTS: In OAG patients of AD, structural changes of the ONH demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over 4 years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of AD, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness. CONCLUSIONS: Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the ONH and macular thickness over 4 years in OAG patients of AD compared with ED. These data suggest that ocular vascular health may be a more influential contributing factor in the pathophysiology of OAG in patients of AD compared with ED. PMID- 27561104 TI - Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption. AB - Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID- 27561106 TI - Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty. AB - The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA sequencing. Fifteen patients were selected based on the histological results and were divided into 2 groups. Seven were classified as belonging to the high infertility risk (HIR) and 8 to the low infertility risk (LIR) group. Cryptorchid boys in the HIR group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini-puberty. This group of patients will be infertile despite successful surgery. The new important finding was a decreased PROK2, CHD7, FGFR1, and SPRY4 gene expression in the HIR group. Furthermore, identification of multiple differences in gene expression between HIR and LIR groups underscores the importance of an intact hypothalamic-pituitary-gonadal axis for fertility development. Our RNA profiling data strongly support the theory that in the HIR group of cryptorchid boys insufficient PROK2/CHD7/FGFR1/SPRY4 gene expression induces deficient LH secretion, resulting in impaired mini-puberty and infertility. We therefore recommend hormonal treatment for this cohort of cryptorchid boys with defective mini-puberty following a seemingly successful orchidopexy. PMID- 27561105 TI - Calreticulin is highly expressed in pancreatic cancer stem-like cells. AB - Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). A P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2-D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in the CRThigh /CD44v9low population was much higher than that in the CRTlow /CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy. PMID- 27561107 TI - Identification and Expression Analysis of Candidate Odorant-Binding Protein and Chemosensory Protein Genes by Antennal Transcriptome of Sitobion avenae. AB - Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) of aphids are thought to be responsible for the initial molecular interactions during olfaction that mediate detection of chemical signals. Analysis of the diversity of proteins involved comprises critical basic research work that will facilitate the development of sustainable pest control strategies. To help us better understand differences in the olfactory system between winged and wingless grain aphids, we constructed an antennal transcriptome from winged and wingless Sitobion avenae (Fabricius), one of the most serious pests of cereal fields worldwide. Among the 133,331 unigenes in the antennal assembly, 13 OBP and 5 CSP putative transcripts were identified with 6 OBP and 3 CSP sequences representing new S. avenae annotations. We used qPCR to examine the expression profile of these genes sets across S. avenae development and in various tissues. We found 7 SaveOBPs and 1 SaveCSP were specifically or significantly elevated in antennae compared with other tissues, and that some transcripts (SaveOBP8, SaveCSP2 and SaveCSP5) were abundantly expressed in the legs of winged or wingless aphids. The expression levels of the SaveOBPs and SaveCSPs varied depending on the developmental stage. Possible physiological functions of these genes are discussed. Further molecular and functional studies of these olfactory related genes will explore their potential as novel targets for controlling S. avenae. PMID- 27561108 TI - Multilocus Analyses Reveal Postglacial Demographic Shrinkage of Juniperus morrisonicola (Cupressaceae), a Dominant Alpine Species in Taiwan. AB - Postglacial climate changes alter geographical distributions and diversity of species. Such ongoing changes often force species to migrate along the latitude/altitude. Altitudinal gradients represent assemblage of environmental, especially climatic, variable factors that influence the plant distributions. Global warming that triggered upward migrations has therefore impacted the alpine plants on an island. In this study, we examined the genetic structure of Juniperus morrisonicola, a dominant alpine species in Taiwan, and inferred historical, demographic dynamics based on multilocus analyses. Lower levels of genetic diversity in north indicated that populations at higher latitudes were vulnerable to climate change, possibly related to historical alpine glaciers. Neither organellar DNA nor nuclear genes displayed geographical subdivisions, indicating that populations were likely interconnected before migrating upward to isolated mountain peaks, providing low possibilities of seed/pollen dispersal across mountain ranges. Bayesian skyline plots suggested steady population growth of J. morrisonicola followed by recent demographic contraction. In contrast, most lower-elevation plants experienced recent demographic expansion as a result of global warming. The endemic alpine conifer may have experienced dramatic climate changes over the alternation of glacial and interglacial periods, as indicated by a trend showing decreasing genetic diversity with the altitudinal gradient, plus a fact of upward migration. PMID- 27561109 TI - Uniparental ancestry markers in Chilean populations. AB - The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curico, Cauquenes, Valdivia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers. PMID- 27561110 TI - Familial Dysautonomia: Mechanisms and Models. AB - Hereditary Sensory and Autonomic Neuropathies (HSANs) compose a heterogeneous group of genetic disorders characterized by sensory and autonomic dysfunctions. Familial Dysautonomia (FD), also known as HSAN III, is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population. The major features of the disease are already present at birth and are attributed to abnormal development and progressive degeneration of the sensory and autonomic nervous systems. Despite clinical interventions, the disease is inevitably fatal. FD is caused by a point mutation in intron 20 of the IKBKAP gene that results in severe reduction in expression of IKAP, its encoded protein. In vitro and in vivo studies have shown that IKAP is involved in multiple intracellular processes, and suggest that failed target innervation and/or impaired neurotrophic retrograde transport are the primary causes of neuronal cell death in FD. However, FD is far more complex, and appears to affect several other organs and systems in addition to the peripheral nervous system. With the recent generation of mouse models that recapitulate the molecular and pathological features of the disease, it is now possible to further investigate the mechanisms underlying different aspects of the disorder, and to test novel therapeutic strategies. PMID- 27561111 TI - The role of natural selection in human evolution - insights from Latin America. AB - A brief introduction considering Darwin's work, the evolutionary synthesis, and the scientific biological field around the 1970s and subsequently, with the molecular revolution, was followed by selected examples of recent investigations dealing with the selection-drift controversy. The studies surveyed included the comparison between essential genes in humans and mice, selection in Africa and Europe, and the possible reasons why females in humans remain healthy and productive after menopause, in contrast with what happens in the great apes. At the end, selected examples of investigations performed in Latin America, related to the action of selection for muscle performance, acetylation of xenobiotics, high altitude and tropical forest adaptations were considered. Despite dissenting views, the influence of positive selection in a considerable portion of the human genome cannot presently be dismissed. PMID- 27561113 TI - 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency. AB - Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID- 27561115 TI - The Role of Emergent Bilingualism in the Development of Morphological Awareness in Arabic and Hebrew. AB - PURPOSE: The purpose of the present study was to investigate the role of dual language development and cross-linguistic influence on morphological awareness in young bilinguals' first language (L1) and second language (L2). We examined whether (a) the bilingual children (L1/L2 Arabic and L1/L2 Hebrew) precede their monolingual Hebrew- or Arabic-speaking peers in L1 and L2 morphological awareness, and (b) 1 Semitic language (Arabic) has cross-linguistic influence on another Semitic language (Hebrew) in morphological awareness. METHOD: The study sample comprised 93 six-year-old children. The bilinguals had attended bilingual Hebrew-Arabic kindergartens for 1 academic year and were divided into 2 groups: home language Hebrew (L1) and home language Arabic (L1). These groups were compared to age-matched monolingual Hebrew speakers and monolingual Arabic speakers. We used nonwords similar in structure to familiar words in both target languages, representing 6 inflectional morphological categories. RESULTS: L1 Arabic and L1 Hebrew bilinguals performed significantly better than Arabic- and Hebrew-speaking monolinguals in the respective languages. Differences were not found between the bilingual groups. We found evidence of cross-linguistic transfer of morphological awareness from Arabic to Hebrew in 2 categories-bound possessives and dual number-probably because these categories are more salient in Palestinian Spoken Arabic than in Hebrew. CONCLUSIONS: We conclude that children with even an initial exposure to L2 reveal acceleration of sensitivity to word structure in both of their languages. We suggest that this is due to the fact that two Semitic languages, Arabic and Hebrew, share a common core of linguistic features, together with favorable contextual factors and instructional factors. PMID- 27561114 TI - Bisphenol A induces spermatocyte apoptosis in rare minnow Gobiocypris rarus. AB - Bisphenol A (BPA) is an endocrine disruptor, and could induce germ cells apoptosis in the testis of mammals. But whether it could affect fish in the same mechanism has not' been studied till now. In the present study, to investigate the influence of BPA on testis germ cells in fish, adult male rare minnow Gobiocypris rarus were exposed to 225MUgL(-1) (0.99MUM) BPA for 1, 3 and 9 weeks. Through TdT-mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM) analysis, we found that the amount of apoptotic spermatocytes significantly increased in a time dependent manner following BPA exposure. Western Blot results showed that the ratio of Bcl2/Bax, the important apoptosis regulators in intrinsic mitochondrial apoptotic pathway, was significantly decreased. qPCR showed that mRNA expression of several genes in mitochondrial apoptotic pathway including bcl2, bax, casp9, cytc and mcl1b were significantly changed following BPA exposure. In addition, mRNA expression of meiosis regulation genes (kpna7 and wee2), and genes involved in both apoptosis and meiosis (birc5, ccna1, and gsa1a) were also affected by BPA. Taken together, the present study demonstrated that BPA could induce spermatocytes apoptosis in rare minnow testis, and the apoptosis was probably under regulation of intrinsic mitochondrial apoptotic pathway. Moreover, the spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest. PMID- 27561116 TI - Treatment of Postextraction Sites With Allograft-Stabilized Dental Implants: A Clinical Case Series. AB - PURPOSE: Additional grafting procedures for the treatment of extremely atrophic jaws may be demanding, expensive, and sometimes require long time and multiple surgical sessions, which may reduce patient's acceptance and quality of life. This study evaluated the outcomes of 10 patients with extensive alveolar bone defects in the posterior jaws, treated in a single surgical session with grafting and implants. MATERIALS AND METHODS: Ten consecutive patients were treated within 3 months of extraction. After ridge exposure, implants were positioned in 4-wall defects without contact with pristine bone, and mineralized particulate allograft packed around to stabilize them. Sites were covered with resorbable membranes and soft tissues were sutured tension-free. Five months later, implants were restored in centric occlusion. RESULTS: At uncovering, newly formed bone filled all defects and all implants resisted at 30 Ncm of reverse torque. No complication was recorded throughout the study; survival rate was 100% for both implants and grafts. After 24 months of follow-up, mean periimplant bone level change was 0.15 +/- 0.53 mm and mean bone gain at the defect site was 11.62 +/- 1.04 mm. CONCLUSION: Rehabilitation of wide postextraction defects may achieve successful outcomes using allograft and a special implant design, even in the absence of optimal primary stability. PMID- 27561112 TI - Microsatellite markers: what they mean and why they are so useful. AB - Microsatellites or Single Sequence Repeats (SSRs) are extensively employed in plant genetics studies, using both low and high throughput genotyping approaches. Motivated by the importance of these sequences over the last decades this review aims to address some theoretical aspects of SSRs, including definition, characterization and biological function. The methodologies for the development of SSR loci, genotyping and their applications as molecular markers are also reviewed. Finally, two data surveys are presented. The first was conducted using the main database of Web of Science, prospecting for articles published over the period from 2010 to 2015, resulting in approximately 930 records. The second survey was focused on papers that aimed at SSR marker development, published in the American Journal of Botany's Primer Notes and Protocols in Plant Sciences (over 2013 up to 2015), resulting in a total of 87 publications. This scenario confirms the current relevance of SSRs and indicates their continuous utilization in plant science. PMID- 27561117 TI - Association Between County-Level Characteristics and Eye Care Use by US Adults in 22 States After Accounting for Individual-Level Characteristics Using a Conceptual Framework. AB - Importance: Individual-level characteristics are associated with eye care use. The influence of contextual factors on vision and eye health, as well as health behavior, is unknown. Objective: To examine the association between county-level characteristics and eye care use after accounting for individual-level characteristics using a conceptual framework. Design, Setting, and Participants: This investigation was a cross-sectional study of respondents 40 years and older participating in the Behavioral Risk Factor Surveillance System surveys between 2006 and 2010 from 22 states that used the Visual Impairment and Access to Eye Care module. Multilevel regressions were used to examine the association between county-level characteristics and eye care use after adjusting for individual level characteristics (age, sex, race/ethnicity, educational attainment, annual household income, employment status, health care insurance coverage, eye care insurance coverage, personal established physician, poor vision or eye health, and diabetes status). Data analysis was performed from March 23, 2014, to June 7, 2016. Main Outcomes and Measures: Eye care visit and receipt of a dilated eye examination in the past year. Results: Among 117 295 respondents who resided in 828 counties, individual-level data were obtained from the Behavioral Risk Factor Surveillance System surveys. All county-level variables were aggregated at the county level from the Behavioral Risk Factor Surveillance System surveys except for a high geographic density of eye care professionals, which was obtained from the 2010 Area Health Resource File. After controlling for individual-level characteristics, the odds of reporting an eye care visit in the past year were significantly higher among people living in counties with high percentages of black individuals (adjusted odds ratio [aOR], 1.12; 95% CI, 1.01-1.24; P = .04) or low-income households (aOR, 1.12; 95% CI, 1.00-1.25; P = .045) or with a high density of eye care professionals (aOR, 1.18; 95% CI, 1.07-1.29; P < .001) than among those living in counties with the lowest tertile of each county-level characteristic. The odds of reporting receipt of a dilated eye examination in the past year were also higher among people living in counties with the highest percentages of black individuals (aOR, 1.20; 95% CI, 1.07-1.34; P = .002) or low income households (aOR, 1.17; 95% CI, 1.04-1.32; P = .01). However, the odds of reported receipt of a dilated eye examination in the past year were lower in counties with the highest percentages of people with poor vision and eye health compared with counties with lower percentages (aOR, 0.85; 95% CI, 0.77-0.94; P = .002). Conclusions and Relevance: Contextual factors, measured at the county level, were associated with eye care use independent of individual-level characteristics. The findings suggest that, while individual characteristics influence health care use, it is also important to address contextual factors to improve eye care use and ultimately vision health. PMID- 27561118 TI - Sexual Abuse in Cameroon: A Four-Year-Old Girl Victim of Rape in Buea Case Study. AB - A young girl was brought to the emergency unit after suffering sexual abuse by an older male. Additional abuses against women and girls include physical beating, forced marriage, female genital mutilation, breast ironing, widow's rites, psychological abuse, and discrimination in education, finance, employment, and legal access. Cameroon has adopted strategies aimed at eliminating violence against women, including ratification of international policies, penal codes, and support of local and international efforts that promote women; however, many of the laws remain in name only and are rarely enforced, given women's lack of financial access to quality lawyers and an unsympathetic male-dominated police force. Underreporting and culturally accepted abuses remain a challenge, too, as the country seeks to understand the extent of abuses and how to effectively fight against them. A complete paradigm shift in cultural attitude toward the female gender is required for abuses to cease. PMID- 27561119 TI - The Impact of High-Profile Sexual Abuse Cases in the Media on a Pediatric Emergency Department. AB - High-profile media cases of sexual abuse may encourage disclosures of abuse from victims of unrelated assaults and also influence parental concerns, leading to increased emergency department visits. In the region of the study authors' institution, there are two recent high-profile sexual abuse cases with media coverage: Earl Bradley, a Delaware pediatrician, and Jerry Sandusky, a Pennsylvania college football coach. This is a retrospective cohort study of children evaluated for sexual abuse at a pediatric emergency department. Patients were classified as either presenting during a media period or non-media period. The media periods were one-month periods immediately following breaking news reports, when the cases were highly publicized in the media. The non-media periods were the 12-month periods directly preceding the first reports. The median number of emergency department visits per month during a non-media period was 9 visits (interquartile range 6-10). There were 11 visits in the month following the Sandusky case and 13 visits following the Bradley case. There was no statistical difference in number of emergency department visits for sexual abuse between the periods (p = .09). These finding have implications regarding use of resources in pediatric EDs after high-profile sexual abuse cases. PMID- 27561120 TI - A Psychosocial Understanding of Child Sexual Abuse Disclosure Among Female Children in South Africa. AB - Child sexual abuse is endemic in South Africa, driven by high levels of gender based violence and underscored by structural and social factors. This article aims to develop an understanding of the process of disclosure in a sample of female children and their caregivers. In-depth semistructured interviews were conducted with 31 female children aged 8-17 years and their caregivers at 3 intervals after presentation to a sexual assault treatment center. Nearly half of the children failed to disclose the sexual abuse immediately, fearing caregivers' reaction. Most children purposefully disclosed to a confidant through a process of identifying an intermediary to tell caregivers on their behalf. The process of disclosure was influenced by multiple factors, such as a fear of the caregiver's reaction and disbelief, which is related to parental style. Disclosure was found to be a dynamic process that unfolds and not a single or static event and influenced by multiple factors which all impact on recovery. Our findings highlight the need to address social norms on sexual abuse in order to improve responses to disclosure to facilitate post-sexual-abuse adjustment for the child and the family. PMID- 27561121 TI - "I Only Want to Know What You Know": The Use of Orienting Messages During Forensic Interviews and Their Effects on Child Behavior. AB - The purpose of this research was to evaluate orienting messages within the CornerHouse Forensic Interview Protocol in two formats: provided both at the outset and as needed throughout the interview compared to previous practice in which orienting messages were provided only as the opportunity arose. Through the content analysis of 120 videotaped forensic interviews and corresponding case files in which children were interviewed for sexual abuse allegations, results suggest that the use of orienting messages both at the beginning and as needed lead to significantly more autonomous responses from children, that use of more orienting messages was significantly related to more autonomous responses from children, and that the specific orienting messages of "can't/won't say" and "ask me a question" significantly predict more autonomous responses among children. Implications for practice include the use of orienting messages as a way to provide a respectful and safe experience for children participating in forensic interviews. PMID- 27561122 TI - Difficulties in Emotion Regulation as a Mediator of the Relationship Between Child Sexual Abuse Victimization and Sexual Aggression Perpetration in Male College Students. AB - Although numerous studies document a link between child sexual abuse and later sexual assault perpetration in men, little research has examined why this relationship exists. One potential mechanism may be emotional regulation difficulties. The current study utilizes a college sample of 132 men to examine the mediating role of emotion regulation difficulties on the relationship between experiencing child sexual abuse and later sexual aggression. Although emotion regulation difficulties in general was not significantly related to sexual aggression, one facet, impulse control difficulties, emerged as a significant mediator of the relationship between child sexual abuse and sexual aggression. Intervention programs should focus on the care that children receive following sexual abuse, with particular emphasis on how emotion regulation abilities may be impacted. PMID- 27561124 TI - Corrigendum. PMID- 27561123 TI - Knowledge and Skills of Sexual Abuse Prevention: A Study on School-Aged Children in Beijing, China. AB - To examine the level of child sexual abuse prevention knowledge and skills in a sample of school-aged children, a total of 559 children from first to fifth grade were recruited from one primary school in Beijing, China. Participants were asked to finish a questionnaire surveying their knowledge and skills of child sexual abuse prevention. Results showed that accurate rate of knowledge on child sexual abuse prevention were between 44.0% and 80.0%. Percentage of participants having applied the self-protection skills of "saying 'no,'" "going away," and "telling adults" properly in hypothetical situations was 57.4%, 28.3%, and 48.3%, respectively. Third-to-fifth graders had a better performance than first-to second graders, and girls performed better than boys. Findings suggest that Chinese school-aged children are in need of knowledge and skills related to child sexual abuse prevention, and education programs should be developed as soon as possible. PMID- 27561125 TI - Water-mediated aggregation of 2-butoxyethanol. AB - Water plays an important role in mediating hydrophobic interactions, and yet open questions remain regarding the magnitude, and even the sign, of water-mediated contributions to the potential of mean force between a pair of oily molecules dissolved in water. Here, the water-mediated interaction between 2-butoxyethanol (BE) molecules dissolved in water is quantified using Raman multivariate curve resolution (Raman-MCR), molecular dynamics (MD) simulations, and random mixing (RM) predictions. Our results indicate that the number of contacts between BE molecules at concentrations between 0.2 M and 1 M exceeds RM predictions, but is less than some MD predictions. Moreover, the potential of mean force between BE molecules in water has a well depth that is shallower than the direct interaction between 1-ethoxybutane chains in the gas phase, and thus the water-mediated contribution to BE aggregation is repulsive, as it pulls BE molecules apart rather than pushing them together. PMID- 27561126 TI - Discrete polygonal supramolecular architectures of isocytosine-based Pt(ii) complexes at the solution/graphite interface. AB - Polygonal supramolecular architectures of a Pt(ii) complex including trimers, tetramers, pentamers and hexamers were self-assembled via hydrogen bonding between isocytosine moieties; their structure at the solid/liquid interface was unravelled by in situ scanning tunneling microscopy imaging. Density functional theory calculations provided in-depth insight into the thermodynamics of their formation by exploring the different energy contributions attributed to the molecular self-assembly and adsorption processes. PMID- 27561127 TI - Cannibalism versus funerary defleshing and disarticulation after a period of decay: comparisons of bone modifications from four prehistoric sites. AB - OBJECTIVES: Humanly induced modifications on human and non-human bones from four archaeological sites of known funerary rituals (one interpreted as cannibalism and three interpreted as funerary defleshing and disarticulation after a period of decay) were analyzed to ascertain whether macromorphological and micromorphological characteristics of cut marks can be used to distinguish cannibalistic from secondary burial practices. MATERIAL AND METHODS: Four collections were analyzed: the Magdalenian assemblage from Gough's Cave (UK) and the Mesolithic-Neolithic bone samples from Lepenski Vir, Padina and Vlasac (Serbia). A total of 647 cut marks (345 on human and 302 on non-human remains) were imaged and measured using an optical surface measurement system, the Alicona InfiniteFocus, housed at the Natural History Museum (London, UK). RESULTS: The frequency of cut marks at Gough's Cave exceeds 65%, while it is below 1% in the Serbian sites, and no human tooth marks and only one case of percussion damage have been observed on the three Serbian collections. The distribution of cut marks on human bones is comparable in the four assemblages. Cannibalized human remains, however, present a uniform cut mark distribution, which can be associated with disarticulation of persistent and labile articulations, and the scalping and filleting of muscles. For secondary burials where modification occurred after a period of decay, disarticulation marks are less common and the disarticulation of labile joints is rare. The micromorphometric analyses of cut marks on human and non-human remains suggest that cut marks produced when cleaning partially decayed bodies are significantly different from cut marks produced during butchery of fresh bodies. CONCLUSIONS: A distinction between cannibalism and secondary treatment of human bodies can be made based on frequency, distribution and micromorphometric characteristics of cut marks. PMID- 27561128 TI - Impact of maternal cigarette smoke exposure on brain and kidney health outcomes in female offspring. AB - Increased oxidative stress in the brain can lead to increased sympathetic tone that may further induce kidney dysfunction. Previously we have shown that maternal cigarette smoke exposure (SE) leads to significantly increased oxidative stress and inflammation in both brain and kidney, as well as reduced brain and kidney mitochondrial activity. This is closely associated with significant kidney underdevelopment and abnormal function in adulthood in the male offspring. This study aimed to investigate the impact of maternal SE on brain and kidney health in the female offspring. In this study, the mouse dams were exposed to two cigarettes, twice daily for 6 weeks prior to gestation, during pregnancy and lactation. Brains and kidneys from the female offspring were collected at 20 days (P20) and 13 weeks (W13) and were subject to further analysis. We found that mRNA expression of brain inflammatory markers interleukin-1 receptor and Toll-like receptor 4 were significantly increased in the SE offspring at both P20 and W13. Their brain mitochondrial activity markers were however increased at W13 with increased antioxidant activity. Kidney development and function in the female SE offspring were not different from the control offspring. We concluded that although brain inflammatory markers were upregulated in the SE female offspring, they were protected from some of the indicators of brain oxidative stress, such as endogenous antioxidant and mitochondrial dysfunction, as well as abnormal kidney development and function in adulthood. PMID- 27561129 TI - Insights into the in vitro Anticancer Effects of Diruthenium-1. AB - The in vitro anticancer activity of the dinuclear trithiolato-bridged arene ruthenium complex diruthenium-1 (DiRu-1) was evaluated against a panel of human cancer cell lines used as in vitro models for hepatocellular carcinoma (HepG2 cells), estrogen-responsive breast adenocarcinoma (MCF-7 cells), and triple negative breast adenocarcinoma (MDA-MB-231 cells). DiRu-1 is highly cytotoxic to these cell lines, demonstrating half-maximal inhibitory concentrations (IC50 ) in the low-nanomolar range (77+/-1.4 to 268.2+/-4.4 nm). The main molecular mechanisms responsible for the high cytotoxicity of DiRu-1 against the most responsive MCF-7 cell line (IC50 =77+/-1.4 nm) were investigated on the basis of the capacity of DiRu-1 to induce oxidative stress, apoptosis, and DNA damage, and to inhibit the cell cycle and proliferation. The results show that DiRu-1 triggers caspase-dependent apoptosis in MCF-7 cells on both the intrinsic and extrinsic pathways. Moreover, the Ru complex also causes necrosis, mitotic catastrophe, and autophagy. DiRu-1 increases the intracellular levels of reactive oxygen species (ROS), which play a significant role in its cytotoxicity and pro apoptotic activity. An important mechanism of the anticancer activity of DiRu-1 appears to be the induction of DNA lesions, mainly due to apoptotic DNA fragmentation and cell-cycle arrest at the G2 /M checkpoint. These changes are correlated with the concentration of DiRu-1, the duration of the cell treatment, and the post-treatment time. PMID- 27561130 TI - Atomic-Sized Pores Enhanced Electrocatalysis of TaS2 Nanosheets for Hydrogen Evolution. AB - A plasma oxidation method is developed to fabricate atomic-scale pores in the basal planes of electrochemically inert TaS2 nanosheets to functionalize the 2D crystals with high electrocatalysis for hydrogen evolution reaction. Quantitative measurements of under-coordinated atoms at edges of the pores by aberration corrected transmission electron microscopy reveal the intrinsic correlation between the defective atomic sites and electrocatalytic activities of 2D TaS2 . PMID- 27561131 TI - Effect of Incorporation Nanocrystalline Corn Straw Cellulose and Polyethylene Glycol on Properties of Biodegradable Films. AB - This work aimed to study the effect of nanocrystalline corn straw cellulose (NCSC) and polyethylene glycol (PEG) on the properties of biodegradable corn distarch phosphate (CDP) films. The mechanical properties and barrier properties were investigated. Meanwhile, the compatibility, crystallization, thermal stability, and morphological structure of the films were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (X-RD), thermogravimetric (TGA), and scanning electron microscopy (SEM). In contrast with the CDP films, incorporation of NCSC in the films improved their tensile strength (TS) significantly, and incorporation of PEG improved their elongation at break (EAB) significantly else. PEG, CDP, and NCSC (P-CDP/NCSC) blend films had the best barrier properties. The thermal stability of the films was increased by the incorporation of NCSC. X-RD showed that CDP and NCSC (CDP/NCSC) films had higher crystallinity. SEM revealed that all films had smooth surface, while the films presented a uniform network structure through the incorporation of NCSC. PMID- 27561133 TI - Vulvar Concerns in Women With a History of Abdominoplasty: A Case Series. AB - OBJECTIVES: The aim of the study was to present a series of women with a history of traditional abdominoplasty or circumferential abdominoplasty (belt lipectomy) with vulvar concerns and anatomic changes. METHODS: We describe 5 women with a history of abdominoplasty who were referred with symptoms of vulvar pain, dyspareunia, lower urinary tract symptoms, and/or lesion/mass. Physical examination revealed elevation of the clitoris on the pubic symphysis with or without retraction of the clitoral hood in each. RESULTS: Abdominoplasty can result in anatomic changes to the female pubic region after elevation of the mons pubis and consequent elevation of the clitoris with or without retraction of the clitoral hood. Although causation cannot be confirmed from this series, a temporal association of vulvar/clitoral pain, pelvic floor dysfunction, and anatomic alterations with or without lesions after abdominoplasty was present in each case. CONCLUSIONS: Awareness regarding potential sequelae from anatomic alteration may lead to improved patient counseling and modified surgical techniques to avoid significant elevation of the mons pubis and vulvar commissure. PMID- 27561132 TI - Associations between Unconventional Natural Gas Development and Nasal and Sinus, Migraine Headache, and Fatigue Symptoms in Pennsylvania. AB - BACKGROUND: Unconventional natural gas development (UNGD) produces environmental contaminants and psychosocial stressors. Despite these concerns, few studies have evaluated the health effects of UNGD. OBJECTIVES: We investigated associations between UNGD activity and symptoms in a cross-sectional study in Pennsylvania. METHODS: We mailed a self-administered questionnaire to 23,700 adult patients of the Geisinger Clinic. Using standardized and validated questionnaire items, we identified respondents with chronic rhinosinusitis (CRS), migraine headache, and fatigue symptoms. We created a summary UNGD activity metric that incorporated well phase, location, total depth, daily gas production and inverse distance squared to patient residences. We used logistic regression, weighted for sampling and response rates, to assess associations between quartiles of UNGD activity and outcomes, both alone and in combination. RESULTS: The response rate was 33%. Of 7,785 study participants, 1,850 (24%) had current CRS symptoms, 1,765 (23%) had migraine headache, and 1,930 (25%) had higher levels of fatigue. Among individuals who met criteria for two or more outcomes, adjusted odds ratios for the highest quartile of UNGD activity compared with the lowest were [OR (95% CI)] 1.49 (0.78, 2.85) for CRS plus migraine, 1.88 (1.08, 3.25) for CRS plus fatigue, 1.95 (1.18, 3.21) for migraine plus fatigue, and 1.84 (1.08, 3.14) for all three outcomes together. Significant associations were also present in some models of single outcomes. CONCLUSIONS: This study provides evidence that UNGD is associated with nasal and sinus, migraine headache, and fatigue symptoms in a general population representative sample. Citation: Tustin AW, Hirsch AG, Rasmussen SG, Casey JA, Bandeen-Roche K, Schwartz BS. 2017. Associations between unconventional natural gas development and nasal and sinus, migraine headache, and fatigue symptoms in Pennsylvania. Environ Health Perspect 125:189-197; http://dx.doi.org/10.1289/EHP281. PMID- 27561134 TI - 2016 IANS International Guidelines for Practice Standards in the Detection of Anal Cancer Precursors. AB - OBJECTIVES: To define minimum standards for provision of services and clinical practice in the investigation of anal cancer precursors. METHODS: After initial face to face meetings of experts at the International Papillomavirus meeting in Lisbon, September 17 to 21, 2015, a first version was drafted and sent to key stakeholders. A complete draft was reviewed by the Board of the International Anal Neoplasia Society (IANS) and uploaded to the IANS Web site for all members to provide comments. The final draft was ratified by the IANS Board on June 22, 2016. RESULTS: The essential components of a satisfactory high-resolution anoscopy (HRA) were defined. Minimum standards of service provision, basic competencies for clinicians, and standardized descriptors were established. Quality assurance metrics proposed for practitioners included a minimum of 50 HRAs per year and identifying 20 cases or more of anal high-grade squamous intraepithelial lesions (HSILs). Technically unsatisfactory anal cytological samples at first attempt in high-risk populations should occur in less than 5% of cases. Where cytological HSIL has been found, histological HSIL should be identified in >= 90% of cases. Duration of HRA should be less than 15 minutes in greater than 90% of cases. Problematic pain or bleeding should be systematically collected and reported by 10% or lesser of patients. CONCLUSIONS: These guidelines propose initial minimum competencies for the clinical practice of HRA, against which professionals can judge themselves and providers can evaluate the effectiveness of training. Once standards have been agreed upon and validated, it may be possible to develop certification methods for individual practitioners and accreditation of sites. PMID- 27561135 TI - Recurrent Pneumonia in an Infant. PMID- 27561136 TI - Gender differences in the use of alcohol and prescription drugs in relation to job insecurity. Testing a model of mediating factors. AB - BACKGROUND: The results of several studies suggest that economy-related stressors are less distressing for women compared with men. This study proposed to examine the relationship of perceived job insecurity with the use of licit drugs using a theoretical model that considered antecedents and mediators of this association, in order to identify differences between working men and women. METHODS: Using information from the Catalan Health Survey (2010-2014), we selected working individuals aged 16-64 who were primary providers of household income (N=5315). The outcomes were two measures of alcohol consumption (heavy drinking and binge drinking) and the use of hypnotics/sedatives. As antecedents of the exposure to job insecurity we considered the type of contractual relationship and occupational class. The mediating factors were poor mental health, household structure and the hours of housework per week. The theoretical model was assessed using path analysis where the moderating effect of gender was considered in all the associations. RESULTS: No differences in the prevalence of job insecurity were found between men and women (17%). Job insecurity (Odds ratio [OR]=1.35, 95% confidence interval [CI]=1.23-1.48) and house workload (OR=1.01, 95% CI=1.00 1.02) were positively associated with poor mental health, with no significant interactions with gender. Poor mental health was significantly associated with binge drinking (OR=1.23, 95% CI=1.13-1.33) and with the use of hypnotics/sedatives (OR=1.71, 95% CI=1.53-1.91). House workload showed a direct negative association with binge drinking (OR=0.99, 95% CI=0.98-1.00), while those in households with no children were more likely to be binge drinkers, with no significant interactions with gender. An alternative model had better fitting results for heavy drinking. CONCLUSION: No gender differences were found in the association of job insecurity with mental health nor with the use of substances among primary providers of household income, emphasising the importance of social roles when assessing differences in mental health among men and women. PMID- 27561137 TI - Affect Following First Exercise Session as a Predictor of Treatment Response in Depression. AB - OBJECTIVE: Remission rates are low with first-step or even second-step antidepressant treatments. Furthermore, despite extensive investments from National Institutes of Health and from industry, novel treatments are not yet available in clinical care for depression. Predictors of treatment response very early in the course of treatment can avoid unnecessarily lengthy trials with ineffective treatments and reduce the trial and error process. This article examines the expression of positive affect immediately following an acute exercise session at the end of the first exercise session as a predictor of treatment response in the National Institute of Mental Health-funded TREAD (Treatment with Exercise Augmentation for Depression) study, which was conducted from April 2003 to August 2007. METHODS: 122 subjects with DSM-IV-diagnosed major depressive disorder were randomized to public health dose (16 kcal/kg/wk) or low dose (4 kcal/kg/wk) of exercise for 12 weeks. Affect following the first exercise session was assessed using the Positive and Negative Affect Scale (PANAS), and depressive symptoms were assessed weekly using the Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) (primary outcome measure). RESULTS: The PANAS composite affect score (positive-negative total) predicted change in IDS-C score (P < .05), as well as treatment response (P < .02) and remission (P < .03) for those in the high-dose group but not in the low-dose group. CONCLUSIONS: These findings suggest that the composite positive affect following the first exercise session has clinical utility to predict treatment response to exercise in depression and match the "right patient" with the "right" treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00076258. PMID- 27561138 TI - A Systematic Review of the Evidence for Medical Marijuana in Psychiatric Indications. AB - OBJECTIVE: Marijuana has been approved for a number of psychiatric conditions in many states in the US including posttraumatic stress disorder (PTSD), agitation in Alzheimer's disease, and Tourette's disorder. In this systematic review, we examine the strength of evidence for the efficacy of marijuana and other cannabinoids for these psychiatric indications. DATA SOURCES: The literature (MEDLINE) was searched for studies published between January 1980 and March 2015 using search terms related to marijuana and other cannabinoids and the specific diagnosis. STUDY SELECTION: The best quality of evidence, namely placebo controlled, randomized clinical trials (RCTs) and meta-analyses, was sought per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the absence of RCTs, the next best available evidence (eg, observational studies, case reports) was reviewed. Of 170 publications that were screened, 40 were related to the topic, 29 were included in the qualitative synthesis, and 13 studies examined the efficacy of cannabinoids in humans. DATA EXTRACTION: The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. RESULTS: No RCTs have thus far examined the efficacy of marijuana for Tourette's disorder, PTSD, or Alzheimer's disease. Lower-quality studies examined the efficacy of marijuana, Delta9 tetrahydrocannabinol, and nabilone; the strength of evidence for the use of cannabinoids for these conditions is very low at the present time. The consequences of chronic cannabinoid exposure includes tolerance, dependence, and withdrawal. Early and persistent marijuana use has been associated with the emergence of psychosis. Marijuana impairs attention, memory, IQ, and driving ability. CONCLUSIONS: Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- or active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions. Physicians and policy-makers should take into account the limited existing evidence and balance that with side effects before approving medical marijuana for psychiatric indications. PMID- 27561139 TI - Clinicians Should Not Adopt a Single Self-Reported Item as a Screener for Suicide. PMID- 27561140 TI - Dr Green and Colleagues Reply. PMID- 27561141 TI - The Silo Effect in Research on PTSD. PMID- 27561142 TI - Pitfalls With the Unquestioning Use of Statistics. PMID- 27561143 TI - Dr Mazereeuw and Colleagues Reply. PMID- 27561144 TI - Low-Dose d-Cycloserine for Depression? PMID- 27561145 TI - Dr Kantrowitz and Colleagues Reply. PMID- 27561146 TI - Identifying Patients Who Need a Change in Depression Treatment and Implementing That Change. AB - For patients whose depression is difficult to treat or treatment-resistant, physicians must make an educated choice to switch, augment, or combine therapies to help patients adequately respond after initial treatment selections fail. Uncover some of the complexities of this challenging diagnosis by following the case of Robert, a 55-year-old accountant whose inadequate response to treatment by his primary care doctor has prompted a referral to a specialist. PMID- 27561147 TI - The Role of Insomnia in Depression and Anxiety: Its Impact on Functioning, Treatment, and Outcomes. AB - Insomnia is a common yet often unrecognized symptom in patients with depression and anxiety. Because of its association with functional impairment, medical conditions, and disturbances in multiple body systems, insomnia must be included in the treatment of depression and anxiety disorders. If left untreated, insomnia may increase the risk of episode recurrence, severe illness course, and poor treatment response. However, these risks may be diminished with effective insomnia treatment. PMID- 27561148 TI - BDNF Polymorphisms Are Associated With Cognitive Performance in Schizophrenia Patients Versus Healthy Controls. AB - BACKGROUND: Accumulating evidence has shown that brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of schizophrenia. Moreover, BDNF genetic variants, especially the Val66Met polymorphism, may influence specific aspects of human cognition. This study aimed to investigate the potential association of BDNF gene polymorphisms with susceptibility to schizophrenia and cognitive impairments in patients with schizophrenia in a Han Chinese population. METHODS: Four polymorphisms (rs6265, rs12273539, rs10835210, and rs2030324) of the BDNF gene were analyzed in a case-control study of 1,887 Han Chinese individuals (844 patients meeting DSM-IV diagnosis of schizophrenia and 1,043 healthy controls). Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in 598 patients and 434 controls. The current study was conducted from 2008 to 2011. RESULTS: Significant differences in the genotype and allele frequencies between patients and controls were observed only for rs10835210 (both P < .05). Further, we found that the rs10835210 polymorphism had a significant effect on language performance only in schizophrenia (P < .05). However, BDNF rs12273539 played a stronger role in cognitive performance among both patients and healthy controls, especially on attention (P < .001) and the RBANS total score (P < .01). CONCLUSIONS: These findings suggest the role of these BDNF gene variants in susceptibility to schizophrenia and in some aspects of cognitive function. PMID- 27561150 TI - When Should a Patient Be Declared Recovered From a Major Depressive Episode? PMID- 27561149 TI - Paradoxical Trend for Improvement in Mental Health With Aging: A Community-Based Study of 1,546 Adults Aged 21-100 Years. AB - OBJECTIVE: Studies of aging usually focus on trajectories of physical and cognitive function, with far less emphasis on overall mental health, despite its impact on general health and mortality. This study examined linear and nonlinear trends of physical, cognitive, and mental health over the entire adult lifespan. METHODS: Cross-sectional data were obtained from 1,546 individuals aged 21-100 years, selected using random digit dialing for the Successful AGing Evaluation (SAGE) study, a structured multicohort investigation that included telephone interviews and in-home surveys of community-based adults without dementia. Data were collected from 1/26/2010 to 10/07/2011 targeting participants aged 50-100 years and from 6/25/2012 to 7/15/2013 targeting participants aged 21-100 years with an emphasis on adding younger individuals. Data included self-report measures of physical health, measures of both positive and negative attributes of mental health, and a phone interview-based measure of cognition. RESULTS: Comparison of age cohorts using polynomial regression suggested a possible accelerated deterioration in physical and cognitive functioning, averaging 1.5 to 2 standard deviations over the adult lifespan. In contrast, there appeared to be a linear improvement of about 1 standard deviation in various attributes of mental health over the same life period. CONCLUSIONS: These cross-sectional findings suggest the possibility of a linear improvement in mental health beginning in young adulthood rather than a U-shaped curve reported in some prior studies. Lifespan research combining psychosocial and biological markers may improve our understanding of resilience to mental disability in older age and lead to broad-based interventions promoting mental health in all age groups. PMID- 27561151 TI - Dissecting a Genomic Role of BDNF in Schizophrenia and Psychosis. PMID- 27561152 TI - Cardiometabolic Risks in Schizophrenia and Directions for Intervention, 2: Nonpharmacological Interventions. AB - Patients with schizophrenia have increased prevalence rates for many cardiometabolic risks, including the metabolic syndrome, and an increased risk of adverse cardiovascular events, including mortality. Behavioral interventions such as diet and exercise (separately and together) improve physical health outcomes in the general population. There are no studies on dietary guidance as a sole behavioral intervention for patients with schizophrenia. A meta-analysis found that exercise as a sole behavioral intervention does not result in meaningful physical or mental health gains in patients with major mental illness. Another meta-analysis found that combined diet and exercise, along with other behavioral elements, was associated with statistically significant but modest weight reduction (mean = 3.14 kg) in the short to intermediate term, but with no other cardiometabolic risk factor benefits. A large, well-supervised, pragmatic, 1-year randomized controlled trial found that behavioral interventions were not associated with health gains on a 10-year cardiovascular risk index, or on a large range of indices of physical and mental health. An added concern is that patients with schizophrenia are poorly motivated for behavioral interventions and show poor participation in such interventions. Barriers, and means of overcoming these barriers, have been identified for the implementation of behavioral programs to improve physical health in patients with serious mental illness. It remains to be demonstrated, however, that behavioral intervention programs consistently improve cardiovascular health indices in patients with schizophrenia and other major mental illnesses. PMID- 27561153 TI - The Effectiveness of Telepsychiatry-Based Culturally Sensitive Collaborative Treatment for Depressed Chinese American Immigrants: A Randomized Controlled Trial. AB - OBJECTIVE: This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants. METHODS: Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM-IV major depressive disorder (MDD) identified by the Mini-International Neuropsychiatric Interview. Eligible patients were randomized to receive either T-CSCT or treatment as usual (TAU) for 6 months. T-CSCT involves (1) cultural consultation via videoconference and (2) care management. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17); positive response was defined as a >= 50% decrease in HDRS17 score, and remission was defined as HDRS17 score <= 7. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Outcomes were compared using multivariate logistic regression and mixed-model for repeated measures methods. RESULTS: Among participants (N = 190), 63% were female, and the mean (SD) age was 50 (14.5) years. They were randomized to T-CSCT (n = 97; 51%) or TAU (n = 93; 49%). Using multivariate logistic regression analyses, the odds of achieving response and remission were significantly greater for the T-CSCT group compared to the control group (odds ratio [OR] = 3.9 [95% CI, 1.9 to 7.8] and 4.4 [95% CI, 1.9 to 9.9], respectively). Multivariate general linear model analyses showed that patients in the T-CSCT group had significantly greater improvement over time in HDRS17 (F4,95 = 4.59, P = .002), CGI-S (F4,95 = 4.22, P = .003), and CGI-I (F4,95 = 2.95, P = .02) scores. CONCLUSIONS: T-CSCT is effective in improving treatment outcomes of Chinese immigrants with MDD. TRIAL REGISTRATION: ClincialTrials.gov identifier: NCT00854542. PMID- 27561154 TI - Asymmetric Hydrogenation of Azaindoles: Chemo- and Enantioselective Reduction of Fused Aromatic Ring Systems Consisting of Two Heteroarenes. AB - High enantioselectivity was achieved for the hydrogenation of azaindoles by using the chiral catalyst, which was prepared from [Ru(eta(3) -methallyl)2 (cod)] and a trans-chelating bis(phosphine) ligand (PhTRAP). The dearomative reaction exclusively occurred on the five-membered ring, thus giving the corresponding azaindolines with up to 97:3 enantiomer ratio. PMID- 27561156 TI - Influence of Added Soy Presscake and Soy Flour on Some Physical and Sensory Properties of Corn Tortillas. AB - Corn tortillas fortified with soybean presscake (SP) and defatted soy flour (SF) were studied and compared. Texture, including firmness and cohesiveness, and color, using a CIE L* a* b* , were determined instrumentally. Physical properties such as size, thickness, and rollability, were also investigated. A consumer acceptance test was conducted to evaluate the acceptance of tortillas at high levels of soy fortification (35% SF and 40% SP). Tortillas fortified with soy were found to be smaller and thicker with increased firmness and cohesiveness. Tortillas made with SF showed the poorest rollability, and were almost unrollable at high SF fortification levels (30% and 35%). Soy fortified tortillas were more red and yellow than control corn tortillas. In the consumer acceptance test, 40% SP and 35% SF had high overall acceptability scores (6 to 6.6 on a 9-point scale) based on all participants (n = 76). In addition, overall flavor and texture of both soy fortified corn tortillas scored above 6. Thus, while fortification with SP and SF had significant effects on tortilla size, thickness, firmness, cohesiveness, rollability, and color, these changes were acceptable to consumers. PMID- 27561155 TI - Design of cyclized selective melanotropins. AB - This article describes the development of cyclic peptides for G-protein coupled receptors to enable structure-function knowledge and the design of novel therapeutics. One important property of cyclic peptides is that they tend to be resistant to the digestion, enabling them to survive in the human digestive tract. This trait makes them very important as drug leads or as scaffolds which, in theory, can be engineered to incorporate a peptide domain of medicinal value. This is especially important for delivery of peptides that would be destroyed without such implementation. The melanocortin system is the focus of this article, and includes melanotropin ligands and melanocortin receptors. We examine two strategies to constrain the melanotropin peptide backbone. The first is based on global constraint of peptides by cyclization using various kinds of linkers. In the second approach we describe the use of a natural cyclized template, the cyclotide, to graft the melanotropin phamacophore, -His-Phe-Arg-Trp-, to obtain selective drug leads. In these examples the conserved melanocyte stimulating hormone pharmacophore is examined and the modified peptides were synthesized by solid phase methodology. Biological studies confirmed the production of selective, potent and in some cases orally available ligands. PMID- 27561158 TI - Facile one-pot synthesis of carbon/calcium phosphate/Fe3O4 composite nanoparticles for simultaneous imaging and pH/NIR-responsive drug delivery. AB - A facile one-pot synthetic strategy was explored to synthesize carbon/calcium phosphate/Fe3O4 composite nanoparticles (carbon/CaP/Fe3O4 composite NPs). Taking advantage of the unique structure including mesoporous, small CaP and Fe3O4 subunits homogeneously distributed in a carbon matrix, carbon/CaP/Fe3O4 NPs integrate high drug loading, pH/NIR-sensitive, photothermal and magnetic properties into one nanoplatform for cancer theranostics. PMID- 27561157 TI - Beneficial effect of aspirin against interferon-alpha-2b-induced depressive behavior in Sprague Dawley rats. AB - Accumulating data advocates that inflammatory mediators may contribute to depression in experimental models as well as in humans. Nonetheless, whether anti inflammatory treatments can prevent depression still remains controversial. To substantiate our hypothesis, we used an interferon-alpha-2b model of depression using Sprague Dawley rats. Interferon-alpha-2b is a cytokine which activates immune response and also produces depression. The animals were treated for 21 days with aspirin (10 mg/kg, per oral (p.o.)) dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o.). Amitriptyline was used as reference standard, and given concurrently with aspirin and dexamethasone to examine any synergy. Interferon-alpha-2b (6000 IU/kg, intraperitoneal (i.p.)) was administered in all the above groups daily, except normal control. Tests performed included sucrose preference test, behavioural tests like forced swim test, elevated plus maze, light dark box and locomotor activity along with biochemical estimations like serum cortisol and brain neurotransmitters. The rats in the group treated with Interferon-alpha-2b produced depressive behaviour in rats. We found that animals treated with aspirin decreased immobility time in forced swim test, increased sucrose preference, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was no effect in groups treated with dexamethasone. Our results suggest that aspirin can serve as a potential antidepressant both individually and as adjuvant agent in the treatment of depression. Inhibition of the cyclo-oxygenase-2 levels and prostaglandins concentration or any other potential physiological and biochemical mechanisms may be involved in antidepressant effect. PMID- 27561159 TI - Symbionts modify interactions between insects and natural enemies in the field. AB - Eukaryotes commonly host communities of heritable symbiotic bacteria, many of which are not essential for their hosts' survival and reproduction. There is laboratory evidence that these facultative symbionts can provide useful adaptations, such as increased resistance to natural enemies. However, we do not know how symbionts affect host fitness when the latter are subject to attack by a natural suite of parasites and pathogens. Here, we test whether two protective symbionts, Regiella insecticola and Hamiltonella defensa, increase the fitness of their host, the pea aphid (Acyrthosiphon pisum), under natural conditions. We placed experimental populations of two pea aphid lines, each with and without symbionts, in five wet meadow sites to expose them to a natural assembly of enemy species. The aphids were then retrieved and mortality from parasitoids, fungal pathogens and other causes assessed. We found that both Regiella and Hamiltonella reduce the proportion of aphids killed by the specific natural enemies against which they have been shown to protect in laboratory and cage experiments. However, this advantage was nullified (Hamiltonella) or reversed (Regiella) by an increase in mortality from other natural enemies and by the cost of carrying the symbiont. Symbionts therefore affect community structure by altering the relative success of different natural enemies. Our results show that protective symbionts are not necessarily advantageous to their hosts, and may even behave more like parasites than mutualists. Nevertheless, bacterial symbionts may play an important role in determining food web structure and dynamics. PMID- 27561160 TI - Impact of suture mediated femoral access site closure with the Prostar XL compared to the ProGlide system on outcome in transfemoral aortic valve implantation. AB - BACKGROUND: Management of femoral access site is an important issue in transfemoral transcatheter aortic valve implantation (TAVI) and crucial for acute and long-term outcome. Data on vascular closure devices in this setting are limited. We evaluated safety and efficacy of the Prostar XL compared to the ProGlide suture-based vascular closure device. METHODS AND RESULTS: We enrolled 585 patients undergoing percutaneous transfemoral transcatheter aortic valve implantation (TAVI). Outcomes were defined according to Valve academic research consortium (VARC)-2 criteria. In 237 (40.5%) patients femoral access site closure was performed using the Prostar and in 348 patients (59.6%) using the ProGlide vascular closure device. There was no significant difference in patient baseline characteristics including single and dual antiplatelet therapies. Sheath outer diameter was significantly larger in the ProGlide compared with the Prostar group (7.7+/-1.5 vs. 7.9+/-0.5mm; p=0.001). Closure device failure according to VARC-2 criteria was significantly more frequent with the Prostar versus ProGlide device (19% vs. 4.6%; p<0.01). Need for surgical repair (11.8% vs. 0%, p<0.01), major (12.2% vs. 2.3%, p<0.01) and minor (17.3% vs. 5.7%, p<0.01) vascular complications and bleeding complications (5.5% vs. 2.0%, p=0.02) occurred significantly more often with the Prostar device compared with the ProGlide system. In addition, in-hospital mortality was higher with Prostar compared with ProGlide (5.9% vs. 2.0%; p=0.01). CONCLUSION: Femoral access site closure with the ProGlide device compared with the Prostar device in transfemoral aortic valve implantation was associated with significantly lower rates of closure device failure, minor and major bleedings and a significantly lower in-hospital mortality. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT02162069. PMID- 27561161 TI - Ebstein's anomaly and aortic arch lesions: When right meets left. PMID- 27561162 TI - Kissing balloon inflation in the aortic valve and left main stem: A novel coronary protection technique. PMID- 27561163 TI - Right ventricular evaluation to improve survival outcome in patients with severe functional mitral regurgitation and advanced heart failure undergoing MitraClip therapy. AB - BACKGROUND: Percutaneous mitral valve repair (PMVR) is a new option for high risk patients with functional mitral regurgitation (FMR) and severely depressed left ventricular (LV) function who are not responding to optimal medical therapy. However patients with end stage heart failure have a high mortality rate despite MitraClip implantation. We sought to identify right ventricular (RV) echocardiographic predictors of outcome in a large cohort of patients with severe FMR and advanced heart failure in order to select the most appropriate candidate who could benefit from this treatment. METHODS: 169 consecutive high surgical risk patients affected by severe FMR underwent PMVR with the MitraClip System. The primary end-point was cardiovascular mortality at the longest available follow-up. RESULTS: The survival free from cardiac death was 97.6% at 30days, 86.7% at 1year, 71.5% at 2years and 61.6% at 3years. Patients who died were significantly older and had more severe comorbidities and signs of more advance heart failure. Independent predictors of cardiovascular mortality were severely impaired renal function [glomerular filtration rate (GFR)<30ml/min; OR=5.46, 95%CI=1.43-20.84, (p=0.01)] and RV systolic dysfunction [peak systolic velocity tissue Doppler imaging (PSVtdi)<9.5cm/s; OR=0.57, 95%CI=0.39-0.82, (p=0.003)]. CONCLUSION: Our study shows the importance of RV systolic function evaluation for the risk stratification of patients with FMR and advanced heart failure undergoing PMVR. Severe right ventricular failure identifies patients with an increased risk for cardiovascular mortality despite MitraClip treatment. RV PSVtdi is the best independent predictor of outcome in these end-stage patients for a threshold value of 9.5cm/s. PMID- 27561164 TI - Pharmacological evaluation of novel alagebrium analogs as methylglyoxal scavengers in vitro in cardiac myocytes and in vivo in SD rats. AB - BACKGROUND: Methylglyoxal (MG) is a byproduct of glucose metabolism and an inducer of advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of diabetes as well as hypertension. Most of the currently available MG scavengers are non-specific and have other effects as well. Alagebrium (ALA), developed by Alteon Corporation is a MG scavenger. Thus the aim of the present study was to investigate the potential of novel ALA analogs as possible MG scavengers and whether they could prevent any deleterious effects of MG. METHODS AND RESULTS: MG levels were measured by HPLC. The different biochemical and molecular parameters were measured by assay kits, RT-PCR and immunocytochemistry. Out of the 15 ALA analogs tested in vitro, compound no. 13 was found to be an effective inhibitor of MG in a concentration and time dependent manner. Compound no. 13 significantly attenuated the MG levels in vitro in MG treated cultured H9C2 cardiomyocytes as well as in vivo in MG treated SD rats. MG induced oxidative stress and apoptosis were attenuated by pretreatment of H9C2 cardiac myocytes with compound no. 13. MG induced cardiac hypertrophy and apoptosis were also attenuated by treating MG treated SD rats with compound no. 13. CONCLUSION: Our results indicate compound 13 as an effective inhibitor of MG in vitro in cultured cardiomyocytes and in vivo in SD rats and thus it may prove very useful in blocking the multiple deleterious effects of MG, including AGEs and vascular complications of diabetes. PMID- 27561165 TI - Prominent left ventricular trabeculations in competitive athletes: A proposal for risk stratification and management. AB - BACKGROUND: Recently, an unexpectedly large prevalence of Left Ventricular Non Compaction (LVNC) has been reported in athletes, raising the question of the appropriateness of current diagnostic criteria. We sought to describe prevalence and clinical characteristics of athletes with suspected LVNC in a large cohort of Olympic athletes. METHODS: Over 29months, 2501 consecutive athletes underwent a cardiac evaluation including physical examination, ECG, exercise test and echocardiography. Additional investigations (Cardiac Magnetic Resonance and/or genetic testing) were selectively performed in athletes with abnormal ECGs, ventricular arrhythmias, borderline LV dysfunction or positive family history. RESULTS: Of the 2501 athletes, 36 (1.4%) showed prominent trabeculations suggestive for LVNC. Of these, 3 (0.1%) were considered to be affected by LVNC, based on presence of LV dysfunction (ejection fraction<50%) and/or positive family history and genetic testing; these athletes were cautiously restricted from competitions and entered a clinical follow-up program. The remaining 33 athletes, in the absence of LV impairment or familial cardiac diseases, were considered normal (n=24) or unlikely affected (n=9), regardless of the extent of the trabeculations. CONCLUSIONS: In a large athlete population, a marked LV trabecular pattern was seen in 1.4%. Only a small subset of these athletes (0.1%) showed familial, clinical and morphologic changes supporting the diagnosis of LVNC. In the vast majority of the athletes, the increased trabeculations were not associated with LV dysfunction and/or positive family history, likely representing a morphologic LV variant, deprived of clinical significance. PMID- 27561166 TI - Prognostic value of cardiopulmonary exercise testing in Idiopathic Dilated Cardiomyopathy. AB - BACKGROUND: Although cardiopulmonary exercise testing (CPET) is considered as an important tool in risk stratification of patients with heart failure (HF), prognostic data in the specific setting of Idiopathic Dilated Cardiomyopathy (iDCM) are still undetermined. The aim of the study was to test the prognostic value of CPET in a large cohort of iDCM patients. METHODS AND RESULTS: We analyzed 381 iDCM patients who consecutively performed CPET. The study end-point was a composite of cardiovascular death/urgent heart transplantation (CVD/HTx). In the overall population the average values of peak oxygen consumption (peak VO2/kg) and percent-predicted peak VO2 (peak VO2%) were 17.1+/-5.1ml/kg/min and 59+/-15%, respectively. Mean VE/VCO2 slope was 29.8+/-6.1. During a median follow up of 47months (interquartile range 23-84), 83 patients experienced CVD/HTx. Peak VO2% (Area Under the Curve [AUC] 0.74; 95% CI 0.71-0.85, p<0.001) and VE/VCO2 slope (AUC 0.78; 95% CI 0.74-0.84, p<0.001) were more accurate in predicting CVD/HTx compared to peak VO2/kg (AUC 0.60; 95% CI 0.54-0.68, p=0.003) (p<0.001 for both comparisons). The most accurate threshold values for outcome prediction in our iDCM cohort were <60% for peak VO2% and >29 for VE/VCO2 slope. At multivariable analysis peak VO2% and VE/VCO2 slope were the strongest predictors of CVD/HTx, either as continuous and categorical variables, whereas peak VO2/kg was not independently related with prognosis. CONCLUSION: In a large population of iDCM patients peak VO2% and VE/VCO2 slope emerged as the strongest prognostic CPET variables. Prospective studies will be necessary to confirm these data. PMID- 27561167 TI - Do randomized clinical trial selection criteria reflect levels of risk as observed in a general population of acute myocardial infarction survivors? The PEGASUS trial in the light of the FAST-MI 2005 registry. AB - BACKGROUND: Few clinical trials have focused on populations with a history of distant myocardial infarction (MI). The PEGASUS trial assessed the impact of dual antiplatelet therapy in such patients, selected by enrichment criteria of high cardiovascular risk. Whether the PEGASUS population reflects the risk of a broader post-MI population is questionable. We analyzed whether 4-year mortality of a routine-practice population would differ according to the inclusion and exclusion criteria used in PEGASUS. METHODS: FAST-MI is a nationwide French registry recruiting acute MI patients in November 2005; 2490 patients alive and without recurrent MI at one year were classified into three groups: Group 1 ("PEGASUS-like" population; n=1395; 56%), Group 2 (population having >=1 exclusion criterion for the trial; n=677; 27%), and group 3 (population meeting neither the PEGASUS inclusion nor exclusion criteria; n=418, 17%). RESULTS: Group 1 patients were older than Group 3 patients, with higher GRACE scores, more comorbidity, and less STEMI, but were younger than the PEGASUS trial population. Enrichment criteria successfully defined a population at higher risk: 4-year survival 83% in Group 1, 97% in Group 2, and 68% in Group 3 (P<0.001). Among risk enrichment criteria, age alone was highly discriminant: in PEGASUS-like patients, survival was 78% in those >=65 versus 94% in those <65years. CONCLUSIONS: Enrichment criteria used in PEGAGUS succeed in defining a population at increased risk in patients with prior MI, age being the most discriminant factor. The trial population, however, was notably younger and more masculine than the corresponding real-life population in France. Clinicaltrials.govnumber:NCT00673036. PMID- 27561168 TI - A Brazilian perspective for the use of bovine heparin in open heart surgery. PMID- 27561169 TI - Bioresorbable vascular scaffolds for the treatment of coronary artery disease: what have we learned from randomized-controlled clinical trials? AB - Although current everolimus-eluting coronary stents have shown improved event free survival within the first year following implantation compared with bare metal stents or earlier generation drug-eluting stents, they remain associated with an ongoing risk for adverse outcomes (thrombosis, myocardial infarction, and restenosis) beyond 1 year at rates similar to those observed following bare-metal stent deployment. This ongoing very late hazard has been attributed to the permanent presence of the metal frame and/or polymer in these stents. The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) has been developed to provide mechanical support and drug-delivery functions similar to metallic drug-eluting stents, followed by complete resorption with recovery of more normal vascular structure and function, thus avoiding the limitations associated with permanent metallic endovascular prostheses. Absorb BVS has shown safety and efficacy in the dedicated clinical trial development program of Abbott Vascular and in an array of investigator-sponsored studies involving a broad spectrum of clinical (patient) as well as coronary anatomic complexity. Longer term evidence, largely limited to single-arm studies, appears to reflect durable safety and efficacy and suggests Absorb BVS to be an attractive therapeutic option. Interim evidence from a series of randomized-clinical trials (RCTs) comparing Absorb BVS with the Xience cobalt-chromium metallic everolimus-eluting stent has shown noninferiority of Absorb BVS with respect to target lesion failure (composite occurrence of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target lesion revascularization) beyond the first year, with no statistically significant differences in other safety/efficacy measures. However, concerns do exist in terms of increased rates of scaffold thrombosis, the risk for which may be mitigated by improved patient and lesion selection, procedural technique, and device iteration. We provide an overview of the evolution of percutaneous coronary intervention, in-vivo characterization of Absorb BVS resorption, and a summary with a critical evaluation of available evidence from RCTs, pooled analyses, and meta-analyses of RCTs for the safety and efficacy of Absorb BVS obtained primarily following the treatment of noncomplex coronary lesions in patients with stable ischemic heart disease and/or stabilized acute coronary syndromes. PMID- 27561170 TI - Financial Relationships With Industry Among National Comprehensive Cancer Network Guideline Authors. AB - Importance: Financial conflicts of interest (FCOIs) among authors of clinical practice guidelines have the potential to influence treatment recommendations. Objective: To quantify FCOIs with industry among authors of the National Comprehensive Cancer Network (NCCN) guidelines. Design, Setting, and Participants: We assessed FCOIs occurring during 2014 among NCCN guideline authors in the United States. All were physician members of the NCCN guideline committees for lung, breast, prostate, and colorectal cancer as of the end of 2014. The data source for FCOIs was Open Payments, which is publically reported by the Centers for Medicare and Medicaid Services. This study was cross sectional. Main Outcomes and Measures: The proportion of NCCN authors having FCOIs with industry; the average amount received from industry sources per author. Results: Of 125 guideline authors, 108 (86%) had at least 1 reported FCOI. Authors received an average of $10 011 (range, $0-$106 859) in general payments (GPs), which include consulting, meals, lodging, and similar transfers of value, and $236 066 (range $0-$2 756 713) in industry research payments (RPs), including funding associated with clinical trials. Approximately 84% of authors received GPs, while 47% received RPs. Eight (6%) had FCOIs in excess of the $50 000 net and/or $20 000 single-company maximums stipulated by NCCN. Conclusions and Relevance: Among NCCN guideline authors, FCOIs involving RPs were of greater value, while those involving GPs were more prevalent. Although FCOIs may result from engaging in important scholarship, FCOIs may still influence guideline authors in counterproductive ways. Research is needed to understand how best to manage author FCOIs during guideline creation. PMID- 27561171 TI - Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2. AB - We recently found that the product of the AES gene functions as a metastasis suppressor of colorectal cancer (CRC) in both humans and mice. Expression of amino-terminal enhancer of split (AES) protein is significantly decreased in liver metastatic lesions compared with primary colon tumors. To investigate its downregulation mechanism in metastases, we searched for transcriptional regulators of AES in human CRC and found that its expression is reduced mainly by transcriptional dysregulation and, in some cases, by additional haploidization of its coding gene. The AES promoter-enhancer is in a typical CpG island, and contains a Yin-Yang transcription factor recognition sequence (YY element). In human epithelial cells of normal colon and primary tumors, transcription factor YY2, a member of the YY family, binds directly to the YY element, and stimulates expression of AES. In a transplantation mouse model of liver metastases, however, expression of Yy2 (and therefore of Aes) is downregulated. In human CRC metastases to the liver, the levels of AES protein are correlated with those of YY2. In addition, we noticed copy-number reduction for the AES coding gene in chromosome 19p13.3 in 12% (5/42) of human CRC cell lines. We excluded other mechanisms such as point or indel mutations in the coding or regulatory regions of the AES gene, CpG methylation in the AES promoter enhancer, expression of microRNAs, and chromatin histone modifications. These results indicate that Aes may belong to a novel family of metastasis suppressors with a CpG-island promoter enhancer, and it is regulated transcriptionally. PMID- 27561172 TI - Immunoproteasome beta5i-Selective Dipeptidomimetic Inhibitors. AB - N,C-capped dipeptides belong to a class of noncovalent proteasome inhibitors. Herein we report that the insertion of a beta-amino acid into N,C-capped dipeptides markedly decreases their inhibitory potency against human constitutive proteasome beta5c, while maintaining potent inhibitory activity against human immunoproteasome beta5i, thereby achieving thousands-fold selectivity for beta5i over beta5c. Structure-activity relationship studies revealed that beta5c does not tolerate the beta-amino acid based dipeptidomimetics as does beta5i. In vitro, one such compound was found to inhibit human T cell proliferation. Compounds of this class may have potential as therapeutics for autoimmune and inflammatory diseases with less mechanism-based cytotoxicity than agents that also inhibit the constitutive proteasome. PMID- 27561173 TI - Morphological and Phylogenetic Description of Trypanosoma noyesi sp. nov.: An Australian Wildlife Trypanosome within the T. cruzi Clade. AB - A number of trypanosome isolates from Australian marsupials are within the clade containing the human pathogen Trypanosoma cruzi. Trypanosomes within this clade are thought to have diverged from a common ancestral bat trypanosome. Here, we characterise Trypanosoma noyesi sp. nov. isolated from the critically endangered woylie (Bettongia pencillata) using phylogenetic inferences from three gene regions (18S rDNA, gGAPDH, and CytB) coupled with morphological and behavioural observations in vitro. We also investigated potential vectors and the presence of T. noyesi in the grey-headed flying fox (Pteropus poliocephalus). Phylogenetic analysis revealed T. noyesi and similar genotypes grouped at the periphery of the T. cruzi clade. T. noyesi is morphologically distinct both from other species of Australian trypanosomes and those within the T. cruzi clade. Although trypanosomes were not observed in the digestive tract of ectoparasites and biting flies collected from T. noyesi infected marsupials, tabanid and biting midges tested positive for T. noyesi DNA, indicating they are vector candidates. Tissues from flying foxes were negative for T. noyesi. This study provides novel information on the morphology and genetic variability of an Australian trypanosome within the T. cruzi clade. PMID- 27561174 TI - Incremental Hemodialysis: How I Do It. AB - Incremental hemodialysis (incrHD) is not widely used nor is it well understood. In addition, and perhaps with more impact, governmental regulations in the United States and their consequential influences on dialysis provider organizations have made the practice of incrHD more difficult than traditional thrice weekly in center HD. IncrHD is critically dependent on the amount of residual kidney function (RKF) as well as the individualized goals of end-stage renal disease (ESRD) management. RKF has to be assessed frequently and dialysis adjusted accordingly. Home HD lends itself to an incremental approach more so than in center HD. This may be due to more experience of the provider, more knowledge of the therapy by the patient and family, the availability of dialysis platforms conducive to incrHD, and/or that its less onerous regulation by the government. I have had a long and successful experience performing incremental dialysis (both peritoneal and hemodialysis) and share here my practice strategies and approaches for incrHD. PMID- 27561175 TI - Effect of as-needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder. AB - BACKGROUND: There are no medications approved for as-needed use for feared situations for individuals with social anxiety disorder (SAD). In the present study, intranasal PH94B was provided for use as needed during stressful events. METHODS: Twenty-two subjects were randomized (double-blind) to 2 weeks of treatment with intranasal PH94B or placebo. Following self-administration of medication prior to a feared event, peak levels of anxiety were recorded using the Subjective Units of Distress Scale (SUDS). After 2 weeks, subjects were crossed over to the opposite treatment for 2 weeks. Average peak SUDS during treatment with PH94B and placebo were compared using a paired t-test. RESULTS: Significant differences in favor of PH94B were found on the primary outcome measure: mean peak SUDS change from baseline for all subjects receiving PH94B was 15.6 points versus 8.3 points for placebo (paired t = 3.09, P = .006, effect size of .658). PH94B showed less superiority over placebo when placebo was given second rather than first, likely due to a carryover effect. Looking between groups at just the first 2 weeks of treatment, PH94B also showed trend superiority to placebo on the Liebowitz Social Anxiety Scale (LSAS) (P = .07) and a significant difference on the Patient Global Impression of Change (P = .024) and the LSAS Avoidance subtotal (P = .02). CONCLUSIONS: While further study is needed, these results, combined with earlier findings, suggest that PH94B could represent a useful as-needed treatment for SAD, and continue to validate the nasal chemosensory system as a novel mechanism for medication delivery. PMID- 27561176 TI - Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping. AB - OBJECTIVE: Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). METHODS: Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 * 4-mm, 12 * 4-mm, or 9 * 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. RESULTS: Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 * 4 mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 * 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 * 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 * 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). CONCLUSIONS: Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security. PMID- 27561177 TI - Comparison of Endoscopic Robotic Versus Sternotomy Approach for the Resection of Left Atrial Tumors. AB - OBJECTIVE: Primary cardiac tumors most commonly occur in the left atrium. The aim of this study was to compare outcomes among patients undergoing isolated left atrial tumor resection via sternotomy or robotic approach. METHODS: From 2003 to 2013, 69 patients underwent isolated left atrial tumor resection at 3 affiliated hospitals with either a sternotomy (n = 39) or robotic approach (n = 30). A retrospective review of prospectively collected data was performed, and outcomes were compared between the sternotomy and robotic groups. Univariate and multivariate analyses controlling for pertinent preoperative characteristics were performed. RESULTS: Patients' characteristics in the 2 groups were similar, with the exception of a history of chronic obstructive pulmonary disease (sternotomy, 12.8% vs robotic, 0%; P < 0.04) and elective surgical status (sternotomy, 64.1% vs robotic, 93.3%; P < 0.02). On univariate analysis, robotic-assisted surgery was associated with significantly shorter postoperative mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and a lower rate of perioperative blood transfusion. After controlling for patient comorbidity in a multiple logistic regression model, there remained a trend toward decreased blood transfusions (adjusted odds ratio, 0.33; CI, 0.09-1.20; P = 0.09), shorter ICU (16.3 fewer hours; P = 0.11), and hospital LOS (1.1 fewer days; P = 0.17) in the robotic group. There was one postoperative stroke in the sternotomy group and none in the robotic group (P = 0.21). CONCLUSIONS: Robotic-assisted left atrial tumor resection is feasible and may be associated with a lower incidence of perioperative blood transfusion as well as shorter ventilation time, and shorter ICU and hospital LOS. PMID- 27561178 TI - New, Virtually Wall-less Cannulas Designed for Augmented Venous Drainage in Minimally Invasive Cardiac Surgery. AB - OBJECTIVE: Inadequate venous drainage during minimally invasive cardiac surgery becomes most evident when the blood trapped in the pulmonary circulation floods the surgical field. The present study was designed to assess the in vivo performance of new, thinner, virtually wall-less, venous cannulas designed for augmented venous drainage in comparison to traditional thin-wall cannulas. METHODS: Remote cannulation was realized in 5 bovine experiments (74.0 +/- 2.4 kg) with percutaneous venous access over the wire, serial dilation up to 18 F and insertion of either traditional 19 F thin wall, wire-wound cannulas, or through the same access channel, new, thinner, virtually wall-less, braided cannulas designed for augmented venous drainage. A standard minimal extracorporeal circuit set with a centrifugal pump and a hollow fiber membrane oxygenator, but no in line reservoir was used. One hundred fifty pairs of pump-flow and required pump inlet pressure values were recorded with calibrated pressure transducers and a flowmeter calibrated by a volumetric tank and timer at increasing pump speed from 1500 RPM to 3500 RPM (500-RPM increments). RESULTS: Pump flow accounted for 1.73 +/- 0.85 l/min for wall-less versus 1.17 +/- 0.45 l/min for thin wall at 1500 RPM, 3.91 +/- 0.86 versus 3.23 +/- 0.66 at 2500 RPM, 5.82 +/- 1.05 versus 4.96 +/ 0.81 at 3500 RPM. Pump inlet pressure accounted for 9.6 +/- 9.7 mm Hg versus 4.2 +/- 18.8 mm Hg for 1500 RPM, -42.4 +/- 26.7 versus -123 +/- 51.1 at 2500 RPM, and -126.7 +/- 55.3 versus -313 +/- 116.7 for 3500 RPM. CONCLUSIONS: At the well accepted pump inlet pressure of -80 mm Hg, the new, thinner, virtually wall-less, braided cannulas provide unmatched venous drainage in vivo. Early clinical analyses have confirmed these findings. PMID- 27561179 TI - Polymerization of Acetonitrile via a Hydrogen Transfer Reaction from CH3 to CN under Extreme Conditions. AB - Acetonitrile (CH3 CN) is the simplest and one of the most stable nitriles. Reactions usually occur on the C=N triple bond, while the C-H bond is very inert and can only be activated by a very strong base or a metal catalyst. It is demonstrated that C-H bonds can be activated by the cyano group under high pressure, but at room temperature. The hydrogen atom transfers from the CH3 to CN along the CH???N hydrogen bond, which produces an amino group and initiates polymerization to form a dimer, 1D chain, and 2D nanoribbon with mixed sp(2) and sp(3) bonded carbon. Finally, it transforms into a graphitic polymer by eliminating ammonia. This study shows that applying pressure can induce a distinctive reaction which is guided by the structure of the molecular crystal. It highlights the fact that very inert C-H can be activated by high pressure, even at room temperature and without a catalyst. PMID- 27561181 TI - Profiling and identification of metabolites of isorhynchophylline in rats by ultra high performance liquid chromatography and linear ion trap Orbitrap mass spectrometry. AB - The searching of potentially bioactive metabolites in the biological body is an interesting and meaningful work for the drug study. However, the structural clarification of possible metabolites is one of the most challenging tasks in drug metabolism studies because of the variety of metabolic reactions and complexity of metabolites in vivo. Here, an ultra high performance liquid chromatography/linear ion trap-Orbitrap mass spectrometry (U-HPLC/LTQ-Orbitrap MS) with combination of data post-processing techniques, including extracted ion chromatogram (EIC) and multiple mass defect filters (MMDF), was established for profiling and identification of metabolites of isorhynchophylline (IR) in vivo and in vitro, and the possible metabolic pathways were subsequently proposed after the oral dose of 20mg/kg; A total of 47 metabolites of IR were tentatively identified, including 47, 21, 18, and 25 metabolites in rat urine, plasma, liver and rat liver microsomes (RLM) samples, respectively. To our knowledge, most of them were reported for the first time. Seven metabolic pathways, including dehydrogenation, oxidation, hydrolysis, reduction, demethylation, hydroxylation and glucuronide conjugation were involved in the metabolism. Among them, dehydrogenation, hydrolysis, hydroxylation and oxidation were considered as the main metabolic pathway of metabolism according to metabolic profile of in vivo and in vitro. The relative percentage of each metabolite and main metabolite types were also determined to better understand the metabolic behavior of IR in rats. The newly discovered IR metabolites significantly expanded our understanding and were going to be greatly helpful for the further pharmacokinetic study of IR in vivo. PMID- 27561180 TI - Measles virus selectively blind to signaling lymphocyte activity molecule has oncolytic efficacy against nectin-4-expressing pancreatic cancer cells. AB - Pancreatic cancer is one of the most intractable cancers and has a devastating prognosis; over the past three decades the 5-year survival rate has been <10%. Therefore, development of a novel anticancer treatment for pancreatic cancer is a matter of urgency. We previously developed an oncolytic recombinant measles virus (MV), rMV-SLAMblind, that had lost the ability to bind to its principal receptor, signaling lymphocyte activity molecule (SLAM), but which selectively infected and efficiently killed nectin-4-expressing breast and lung cancer cells. In this study, we analyzed the antitumor effect of this virus against pancreatic cancer. Nectin-4 was expressed on the surface of 4/16 tested pancreatic cancer cell lines, which were efficiently infected and killed by rMV-SLAMblind in vitro. The intratumoral inoculation of rMV-SLAMblind suppressed the growth of KLM1 and Capan 2 cells xenografted in SCID mice. The sequence analysis of MV isolated from the tumor revealed that the designed mutation in the H protein of rMV-SLAMblind had been stably maintained for 47 days after the last inoculation. These results suggest that rMV-SLAMblind is a promising candidate for the novel treatment of pancreatic cancer. PMID- 27561182 TI - An analytical strategy to investigate Semen Strychni nephrotoxicity based on simultaneous HILIC-ESI-MS/MS detection of Semen Strychni alkaloids, tyrosine and tyramine in HEK 293t cell lysates. AB - A Previous metabolomics study has demonstrated that tyrosine metabolism might be disrupted by treating with Semen Strychni on the cell nephrotoxicity model. To investigate the relationship between Semen Strychni alkaloids (SAs) and endogenous tyrosine, tyramine under the nephrotoxicity condition, an HILIC-ESI MS/MS based analytical strategy was applied in this study. Based on the established Semen Strychni nephrotoxicity cell model, strychnine and brucine were identified and screened as the main SAs by an HPLC-Q Exactive hybrid quadrupole Orbitrap mass system. Then, a sensitive HILIC-ESI-MS/MS method was developed to simultaneously monitor strychnine, brucine, tyrosine and tyramine in cell lysate. The analytes were separated by a Shiseido CAPCELL CORE PC (150mm*2.1mm, 2.7MUm) HILIC column in an acetonitrile/0.1% formic acid gradient system. All the calibration curves were linear with regression coefficients above 0.9924. The absolute recoveries were more than 80.5% and the matrix effects were between 91.6%-107.0%. With the developed method, analytes were successfully determined in cell lysates. Decreased levels of tyrosine and tyramine were observed only in combination with increased levels of SAs, indicating that the disturbance of tyrosine metabolism might be induced by the accumulation of SAs in kidney cell after exposure of Semen Strychni. The HILIC-ESI-MS/MS based analytical strategy is a useful tool to reveal the relationships between the toxic herb components and the endogenous metabolite profiling in the toxicity investigation of herb medicines. PMID- 27561183 TI - A rapid and sensitive UHPLC-MS/MS assay for the determination of trelagliptin in rat plasma and its application to a pharmacokinetic study. AB - This study aims to develop and validate a simple, rapid and sensitive ultra performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method for exploring pharmacokinetic characteristics of trelagliptin. Protein precipitation by acetonitrile was used to prepare plasma sample. A RRHD Eclipse Plus C18 (2.1*50mm, 1.8MU) column with gradient mobile phase (containing acetonitrile and 0.1% formic acid) help to achieve the separation of trelagliptin and carbamazepine (IS) with high selectivity. Detection of target fragment ions m/z 358.2->133.9 for trelagliptin, and m/z 237.1->194.0 for IS was performed in positive-ion electrospray ionization mass spectrometry by multiple reaction monitoring. Linear calibration plots were achieved in the range of 5-4000ng/mL for trelagliptin (R(2)=0.999) in rat plasma. The recovery of trelagliptin ranged from 87.8% to 93.7%. The method was showed to be accurate, precise and stable. No obvious matrix effect was found. It has been fully validated and successfully applied to pharmacokinetic study of trelagliptin. PMID- 27561184 TI - Quantitative multiresidue analysis of antibiotics in milk and milk powder by ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometry. AB - A simple and fast multiresidue extraction and purification method was developed for the determination of 61 veterinary drugs, belonging to seven classes, in milk and milk powder. The extraction depends on the acetonitrile solvent, followed by a single step to remove lipids with fatty acid chains using a new reversed phase SPE without traditional pre-equilibration and washing steps before eluting SPE. The purifying lipid effect of the present preparation method was evaluated by comparing the response changes of ion peak areas of the milk endogenous metabolites before and after SPE treatment using ultra-fast LC coupled to tandem quadrupole and TOF MS. Subsequently, UPLC coupled to tandem quadrupole MS was performed for the quantitative analysis of milk and milk powder samples spiked with 61 veterinary drugs, including beta-lactam, macrolide, amide alcohol, forest amine, sulfanilamide, tetracyclines, and quinolones antibiotics. This method is very simple, fast, sensitive, and selective, and allows the good recoveries of all compounds, with a recovery range of 61.5-118.6%, and coefficients of variation of less than 11.6%. The 61 compounds behave in the dynamic range 0.01 200MUgkg(-1), with correlation coefficient >0.99. The limits of quantification for the analytes are in the range 0.01-5.18MUgkg(-1). Finally, this method has been successfully applied to the screening of veterinary drugs in 50 commercial bovine milk and milk powder samples, and ceftiofur and ciprofloxacin were detected in some brand samples. PMID- 27561185 TI - Comparative investigation on the pharmacokinetics of geniposide in type 2 diabetic and normal rats after oral administration of Fructus Gradeniae extract. AB - Fructus Gradeniae, the fruit of Gardenia jasminoides Ellis, was used alone or in combination with other herb medicines in the treatment of type 2 diabetes mellitus in China for a long time. In present investigation, the HPLC method for the determination of geniposide in rat plasma was developed and validated, and the pharmacokinetics of geniposide in type 2 diabetic rats after oral administration of Fructus Gradeniae extract or pure was studied. The results showed that the pharmacokinetic profile (especially the area under the plasma concentration-time curve, AUC) of geniposide in type 2 diabetic rats after orally administered with Fructus Gradeniae extract or pure geniposide was remarkably different from that in normal rats. The results indicated that the increased AUC of geniposide in type 2 diabetic rats did not result from the effects of other components contained in Fructus Gradeniae. It could be speculated that the increased AUC of geniposide might result from the pathological state of type 2 diabetes mellitus which resulted in the pharmacokinetic alterations of geniposide. PMID- 27561187 TI - Residual neurogenesis in chronically epileptic hippocampus of mice. AB - Abnormal hippocampal neurogenesis after acute seizures has been well addressed. However, whether newly generated cells continued to be disturbed even they were born in the chronic stage after pilocarpine-induce status epilepticus has remained elusive. Labeling dividing progenitors and their progeny with retroviral vector expressing green fluorescent protein or proliferation marker 5-bromo-2' deoxyuridine at 3 months post pilocarpine-induced status epilepticus in mice, a spot of newly born neurons exhibiting hilar ectopic location (4.57+/-2.3%), aberrant basal dendrites (8.09+/-1.5%) and abnormal axon sprouting into inner molecular layer of dentate gyrus was identified when examined 6 weeks later. No significant difference on the amount of mossy fiber sprouting was found when cohorts of newborn cells were eliminated by methylazoxymethanol acetate injection initiated at 3 months after SE, suggesting that adult generated neurons in the chronically epileptic hippocampus don't contribute a lot to the mossy fiber sprouting. These results indicated that the aberrant neurogenesis in the chronically epileptic hippocampus occurs only in a small population of newly generated granule cells. PMID- 27561186 TI - Risk of hospitalisation after primary treatment for prostate cancer. AB - OBJECTIVE: To compare the risk of hospitalisation and associated costs in patients after treatment for prostate cancer. PATIENTS AND METHODS: We identified 29 571 patients aged 66-75 years without significant comorbidity from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database who were diagnosed with localised prostate cancer between 2004 and 2009. We compared the rates of all-cause and treatment-related hospitalisation that occurred within 365 days of the initiation of definitive therapy. We used multivariable logistic regression analysis to identify determinants associated with hospitalisation. RESULTS: Men who underwent radical prostatectomy (RP) rather than radiotherapy (RT) had lower odds of being hospitalised for any cause after therapy [odds ratio (OR) 0.80, 95% confidence interval (CI): 0.74-0.87]. Patients who underwent RP rather than RT had higher odds of being hospitalised for treatment-related complications (OR 1.15, 95% CI: 1.03-1.29). However, men who underwent external beam RT (EBRT)/intensity modulated RT (IMRT) (OR 0.84, 95% CI: 0.72-0.99) had a 16% lower odds of hospitalisation from treatment-related complications than patients undergoing RP. Using propensity score-weighted analyses there was no significant difference in the odds of hospitalisation from treatment-related complications for men who underwent RP vs RT (OR 1.06, 95% CI: 0.92-1.21). Patients hospitalised for treatment-related complications after RT were costlier than patients who underwent RP (Mean $18 381 vs $13 203, P < 0.001). CONCLUSIONS: With the exception of men who underwent EBRT/IMRT, there was no statistically significant difference in the odds of hospitalisation from treatment-related complications. Costs from hospitalisation after treatment were significantly higher for men undergoing RT than RP. Our findings are relevant in the context of penalties linked to hospital readmissions and bundled payment models. PMID- 27561188 TI - Clinical and electrophysiological findings in mesial temporal lobe epilepsy with hippocampal sclerosis, based on the recent histopathological classifications. AB - BACKGROUND: Hippocampal sclerosis (HS) is a common pathology in MTLE, patients may show different surgical outcomes and clinical features. The 2013 ILAE classification subdivides HS into 3 types (HS type 1: severe neuronal loss and gliosis predominantly in CA1 and CA4 regions; - HS type 2: CA1 predominant; HS type 3: CA4 predominant) and includes "gliosis only, as no-HS". The association of clinical and electrophysiological findings with different HS types has not been reported previously in detail. METHODS: 48 patients who had undergone temporal lobectomy with amygdalohippocampectomy due to mesial TLE-HS between February 2014 and February 2016 were included. The patients were divided into five groups: patients with HS ILAE type 1, HS ILAE type 2, HS ILAE type 3, FCD type IIIa, or gliosis/no HS. The correlation between HS ILAE types and clinical/EEG findings in patients with MTLE due to HS was investigated. RESULTS: Of the 48 patients 30 were male. In 23 patients, the resection was on the left side (48%). Three patients had only gliosis, 25 patients had HS ILAE type 1, 7 had HS ILAE type 2, and 4 had HS ILAE type 3. Nine of the 48 patients had cortical lamination abnormalities in the temporal lobe associated with HS (FCD type IIIa). All patients were seizure free for early follow up. There was no association between type of HS in terms of duration of epilepsy, onset age of epilepsy, lateralized or localized semiological findings, or interictal/ictal EEG findings. Family history of epilepsy or SGTCSs were statistically more frequent in patients with types 2 and 3 HS and status epilepticus was more frequent in patients with HS-FCD type IIIa. CONCLUSION: The patients with HS types 2 and 3 have more frequent SGTCS or status epilepticus as well as increased family history of epilepsy. These findings can be helpful in understanding the epileptogenicity-prognoses of HS. PMID- 27561189 TI - Relation of Heavy Alcohol Consumption to QTc Interval Prolongation. AB - Until now, few studies have examined QT intervals in subjects who consume alcohol. We performed this study to evaluate the associations between alcohol consumption and the QTc interval based on a general population. A total of 11,269 adults were examined using a multistage cluster sampling method to select a representative sample of subjects aged >=35 years. Participants were asked to provide information about their alcohol consumption, and all participants received electrocardiograms and echocardiograms. A prolonged QTc interval was defined according to the national guidelines, which specify thresholds of >=460 ms in women and >=450 ms in men. Patients were divided into 3 categories, based on the amount of alcohol they consumed: heavy drinkers (>15 g/day for women and >30 g/day for men), moderate drinkers (<=15 g/day for women and <=30 g/day for men), and nondrinkers (0 g/day). The results showed that the heavy drinkers had longer QTc intervals than did the nondrinkers. Multivariate logistic regression analyses revealed that men who were heavy drinkers had approximately 1.4-fold higher odds of having a prolonged QTc interval (odds ratio 1.431, 95% confidence interval [CI] 1.033 to 1.982, p = 0.031) than nondrinkers; in women, heavy drinkers had ~2.3-fold higher odds of having a prolonged QTc interval (odds ratio 2.344, 95% CI 1.202 to 4.571, p = 0.012) than nondrinkers. Neither men nor women who were moderate drinkers exhibited a significant increase in risk for prolonged QTc interval. In conclusion, heavy alcohol consumption was found to be a risk factor for a prolonged QTc interval. PMID- 27561190 TI - Epidemiology, Management Strategies, and Outcomes of Patients With Chronic Total Coronary Occlusion. AB - Factors influencing the management of patients with chronic total occlusion (CTO) are poorly described. We sought to analyze the clinical and angiographic variables influencing the decision-making process of patients with CTO. Consecutive patients with at least 1 coronary artery CTO were included and categorized as managed either by percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical therapy (MT). Patients with previous CABG were excluded. The CTO SYNTAX score (CTO-SS) was defined as the ratio between the score attributed to the CTO lesion in the SYNTAX score calculation and the total SYNTAX score. Independent predictors of management strategies were sought. A total of 510 patients were included (CTO incidence: 20%): 9% were treated with PCI, 34% with CABG, and 57% with MT. SYNTAX score was lowest in PCI (14.8 [11.0 to 18.5]) and highest in CABG (31.5 [25.0 to 38.8], p <0.0001). PCI was attempted more often in patients with higher CTO-SS (i.e., those with higher contribution to the overall SYNTAX score from the CTO lesion; 88% had a CTO-SS >0.5). Conversely, CABG was preferred in subjects with lower CTO SS (61% had a CTO-SS <=0.5, p <0.0001). Age, ejection fraction, SYNTAX score, and age of the CTO were independent predictors of revascularization. At mid-term follow-up, unsuccessful revascularization or MT was independently associated with death (hazard ratio 7.2, p = 0.0005). In conclusion, CTOs are frequently documented in clinical practice. However, less than a half is revascularized. Management strategies are influenced by angiographic variables such as the SYNTAX score and the newly proposed CTO-SS. PMID- 27561191 TI - Performance of the GRACE Risk Score 2.0 Simplified Algorithm for Predicting 1 Year Death After Hospitalization for an Acute Coronary Syndrome in a Contemporary Multiracial Cohort. AB - The GRACE Risk Score is a well-validated tool for estimating short- and long-term risk in acute coronary syndrome (ACS). GRACE Risk Score 2.0 substitutes several variables that may be unavailable to clinicians and, thus, limit use of the GRACE Risk Score. GRACE Risk Score 2.0 performed well in the original GRACE cohort. We sought to validate its performance in a contemporary multiracial ACS cohort, in particular in black patients with ACS. We evaluated the performance of the GRACE Risk Score 2.0 simplified algorithm for predicting 1-year mortality in 2,131 participants in Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE), a multiracial cohort of patients discharged alive after an ACS in 2011 to 2013 from 6 hospitals in Massachusetts and Georgia. The median age of study participants was 61 years, 67% were men, and 16% were black. Half (51%) of the patients experienced a non-ST-segment elevation myocardial infarction (NSTEMI) and 18% STEMI. Eighty patients (3.8%) died within 12 months of discharge. The GRACE Risk Score 2.0 simplified algorithm demonstrated excellent model discrimination for predicting 1-year mortality after hospital discharge in the TRACE-CORE cohort (c-index = 0.77). The c-index was 0.94 in patients with STEMI, 0.78 in those with NSTEMI, and 0.87 in black patients with ACS. In conclusion, the GRACE Risk Score 2.0 simplified algorithm for predicting 1-year mortality exhibited excellent model discrimination across the spectrum of ACS types and racial/ethnic subgroups and, thus, may be a helpful tool to guide routine clinical care for patients with ACS. PMID- 27561192 TI - Age-Related Differences in 1- and 12-Month Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation (from a Large Multicenter Data Repository). AB - Scarce data are available on the impact of age on transcatheter aortic valve implantation (TAVI) outcomes. We therefore, analyzed 1,845 consecutive patients from 9 Italian centers who underwent TAVI with the Corevalve Revalving System from September 2007 to March 2014; patients were dichotomized according to their age in the date of the procedure, as follows: 75 to 85 years old and >85 years old. End points were defined according to Valve Academic Research Consortium definitions. In-hospital, 30-day, and 1-year clinical and echocardiographic data were available for 100% of the patients included. Propensity matching was performed. Procedural success rates were high (>94%) and comparable between groups. Although worse baseline renal function was observed in the older group, the incidence of acute kidney injury after procedure was comparable (17.1% and 17.4%, respectively for the 75- to 85- and >85-year-old group, p = 0.877); importantly, >99% of acute kidney injury episodes in both groups were grades 1 and 2. Procedural complications rates were low without between-group differences. In-hospital death (3.7% and 4.6%, p = 0.379) and stroke/transient ischemic attack (1.9% and 1.9%, respectively, p = 0.960) were comparable. The 1-year death rates were 14.9% and 17.2% (p = 0.197) in the 75- to 85- and >85-year-old group, respectively. Cardiovascular death was observed in 7.8% and 7% (p = 0.542), while stroke/transient ischemic attack was demonstrated in 5.2% and 4.4% (p = 0.496), respectively. Results were sustained after propensity matching. In conclusion, advanced age did not negatively impact the outcomes of TAVI through 1-year after procedure. PMID- 27561193 TI - One-Year Outcomes After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction With Varying Quantities of Coronary Artery Calcium (from a 13-Year Registry). AB - Coronary artery calcium (CAC) is associated with poor angiographic results and higher rates of complications after percutaneous coronary intervention (PCI). Limited data are available regarding the impact of angiographically evident CAC on long-term outcomes after primary PCI in patients presenting with ST-segment elevation myocardial infarction (STEMI). In this single-center, registry-based retrospective cohort analysis, we analyzed 2,143 consecutive patients presenting with STEMI who underwent primary PCI within 12 hours of symptom onset. Patients were divided based on degree of CAC (determined by visual inspection of angiograms) as follows: (1) moderate-to-severe CAC (n = 306; 14.3%) and (2) minimal-to-none CAC (n = 1,837; 85.7%). The primary end point was all-cause mortality at 1-year after PCI. Patients with moderate-to-severe CAC were older, women, and had higher rates of hypertension, chronic kidney disease, and peripheral vascular disease. Moderate-to-severe CAC was associated with higher rates of anterior myocardial infarction, advanced Killip class, and poor final angiographic results. At 1-year follow-up, rates of all-cause mortality were higher in the moderate-to-severe CAC cohort than those in the minimal-to-none CAC cohort (8.5% vs 4.7%; p = 0.008). However, after accounting for major clinical and angiographic characteristics, moderate-to-severe CAC on presenting STEMI angiogram was no longer predictive of 1-year all-cause mortality. In conclusion, advanced CAC burden occurs in ~15% of patients undergoing primary PCI for STEMI and reflects a marker of adverse prognosis late into follow-up after PCI. PMID- 27561194 TI - Relation of Angina Pectoris to Outcomes, Quality of Life, and Response to Exercise Training in Patients With Chronic Heart Failure (from HF-ACTION). AB - Angina pectoris (AP) is associated with worse outcomes in heart failure (HF). We investigated the association of AP with health-related quality of life (HRQoL), exercise capacity, and clinical outcomes and its interaction with exercise training in an HF population. We grouped 2,331 patients with HF with reduced ejection fraction in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial of usual care +/- exercise training according to whether they had self-reported AP by Canadian classification score. HRQoL and clinical outcomes were assessed by AP status. In HF-ACTION, 406 patients (17%) had AP at baseline (44% with Canadian classification score >=II) with HF severity similar to those without AP. Patients with AP had similar baseline exercise capacity but worse depressive symptoms and HRQoL. AP was associated with 22% greater adjusted risk for all-cause mortality/hospitalizations, driven by hospitalizations. There was significant interaction between baseline AP and exercise training peak VO2 change (p = 0.019) but not other end points. Exercise training was associated with greater peak VO2 improvement after 3 months in patients with AP (treatment effect = 1.25 ml/kg/min, 95% CI 0.6 to 1.9). In conclusion, AP was associated with worse HRQoL and depressive symptoms. Despite greater peak VO2 improvement with exercise training, patients with AP experienced more adverse outcomes. PMID- 27561195 TI - Comparison of Characteristics and Outcomes of Heart Failure Patients With Preserved Versus Reduced Ejection Fraction in a Multiethnic Southeast Asian Cohort. AB - There are few data comparing the patient characteristics and outcomes of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced EF (HFrEF) in Asian cohorts. We aimed to evaluate the prevalence, clinical characteristics, and 1-year outcomes of a well-defined Southeast Asian HFpEF cohort in comparison to an HFrEF cohort. We conducted a retrospective observational study of 1,978 patients discharged from Changi General Hospital, Singapore with a primary diagnosis of HF from 2009 to 2013. About 29% of discharges had HFpEF. Patients with HFpEF were more likely to be women, older age, and have a higher prevalence of hypertension. There were no significant differences in the absolute rates of 30-day outcomes between the 2 groups. The absolute rate of death at 1 year was similar in HFrEF and HFpEF at 17% and 15%, respectively (p = 0.3). After multivariate adjustment, there was no difference in the outcomes of the 2 groups. Atrial fibrillation at baseline was a predictor of death or HF hospitalization in HFpEF but not HFrEF (interaction p = 0.003). In conclusion, in this study of a Southeast Asian population with well-defined HF, we found that the clinical profile of patients with HF was similar to that in the West and 30-day and 1-year mortality and morbidity were not significantly different between cohorts. PMID- 27561196 TI - Diagnosis of Active Infective Endocarditis from Examination of the Toes and Soles. AB - A 72-year-old woman was admitted to our hospital with fever >38 degrees C of unknown origin. Blood cultures were positive in two sets for Staphylococcus aureus. In the third day of admission, her husband drew attention to the presence of some small punctures in her right foot. Several small and non-tender, erythematous and hemorrhagic macular lesions were found on her sole (Janeway lesions). Besides, we detected some painful and palpable, erythematous nodules involving the pads of her toes (Osler nodes). At this point, according to the modified Duke criteria, the clinical diagnosis of definite infective endocarditis might be established. Additionally, the transesophageal echocardiogram just confirmed the presence of a large vegetation attached to the posterior leaflet of the mitral valve. PMID- 27561197 TI - Outcome of Primary Prevention Implantable Cardioverter Defibrillator Therapy According to New York Heart Association Functional Classification. AB - We aimed to assess if the outcome of primary prevention implantable cardioverter defibrillators (ICDs) without cardiac resynchronization therapy is dependent on New York Heart Association (NYHA) class. Among the participants of Defibrillateur Automatique Implantable-Prevention Primaire (DAI-PP; NCT01992458) multicenter cohort study, 155 patients in NYHA class I, 504 in NYHA class II, and 188 in NYHA class III had a QRS width <120 ms and were implanted with an ICD without cardiac resynchronization therapy and, thus, were eligible for the purpose of this analysis. Total and specific mortalities and the incidence of appropriate therapies were assessed for every NYHA. During 2,606 patient-years (3.1 +/- 2.1 years), 104 (12.3%) subjects died and 188 (22.2%) experienced appropriate therapies. After adjustment, overall mortality increased with NYHA class (adjusted hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11 to 2.41, p = 0.014), driven by an increase in cardiovascular death. Conversely, incidence of appropriate ICD intervention was comparable among the 3 NYHA groups (NYHA class I 7.43, NYHA class II 7.91, and NYHA class III 12.10 per 100 patient-years; HR 1.19, 95% CI 0.89 to 1.59, p = 0.231). Incidence of ICD-unresponsive sudden death was very low and also comparable (NYHA class I 0.22, NYHA class II 0.36, and NYHA class III 0.83 per 100 patient-years (HR 6.34, 95% CI 0.32 to 124.49, p = 0.224). No significant differences were observed in the other specific modes of death. In conclusion, although patients in NYHA class III have higher overall mortality, they experience a comparable incidence of appropriate ICD therapies. The low incidence of ICD-unresponsive sudden death in all assessed NYHA classes also supports the efficacy of ICDs, irrespective of NYHA class. PMID- 27561198 TI - Association of SCARB1 Gene Polymorphisms with Virological Response in Chronic Hepatitis C Patients Receiving Pegylated Interferon plus Ribavirin Therapy. AB - The scavenger receptor type B class I(SR-BI) is a receptor for high-density lipoproteins(HDL) and one of entry factors for hepatitis C virus(HCV). We examined the association of single nucleotide polymorphisms(SNPs) of the SCARB1 gene, which encodes SR-BI, with virologic responses to pegylated interferon-based treatment in Asian chronic hepatitis C(CHC) patients. Human genomic and clinical data were collected from 156 consecutive Taiwanese HCV genotype 1 or 2 patients who received pegylated interferon plus ribavirin therapy and 153 non-HCV healthy subjects. Three SNPs(rs10846744, rs5888, and rs3782287) of the SCARB1 gene that have been linked to humans diseases were investigated. rs10846744 rather than rs5888 or rs3782287 was associated with serum HCV RNA level and sustained virologic response(SVR) to pegylated interferon plus ribavirin therapy in CHC patients(GG vs. non-GG genotype, Adjusted Odds Ratio, 95% CI: 0.32, 0.11-0.95, P = 0.039). Among patients with IL28B rs8099917 non-TT genotypes, those with rs10846744 non-GG genotype had a higher SVR rate than those with GG genotypes. In addition, patients with GG genotype had a higher fasting blood glucose level than those with CC genotype. In conclusion, SCARB1 gene polymorphisms may serve as a potential predictor of treatment responses in CHC patients receiving interferon based therapy. (ClinicalTrials.gov number, NCT02714712). PMID- 27561199 TI - Synthesis of (125) I-lamivudine and (125) I-lamivudine-ursodeoxycholic acid codrug. AB - The preparation of (125) I-lamivudine ((125) I-3TC) and (125) I-lamivudine ursodeoxycholic acid codrug ((125) I-3TC-UDCA), suitable for comparative biodistribution studies, is described. The synthesis of the unlabeled precursor 3TC-UDCA proceeds in an 11.6% yield, and the radiolabelling yields for (125) I 3TC and (125) I-3TC-UDCA were 89 and 92%, respectively. The final products are radiochemically pure (greater than 98%). PMID- 27561201 TI - Corrigendum: Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification. PMID- 27561200 TI - Genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA transcriptomes in oxidative and glycolytic skeletal muscles. AB - The physiological, biochemical and functional differences between oxidative and glycolytic muscles play important roles in human metabolic health and in animal meat quality. To explore these differences, we determined the genome-wide landscape of DNA methylomes and their relationship with the mRNA and miRNA transcriptomes of the oxidative muscle psoas major (PMM) and the glycolytic muscle longissimus dorsi (LDM). We observed the hypo-methylation of sub-telomeric regions. A high mitochondrial content contributed to fast replicative senescence in PMM. The differentially methylated regions (DMRs) in promoters (478) and gene bodies (5,718) were mainly enriched in GTPase regulator activity and signaling cascade-mediated pathways. Integration analysis revealed that the methylation status within gene promoters (or gene bodies) and miRNA promoters was negatively correlated with mRNA and miRNA expression, respectively. Numerous genes were closely related to distinct phenotypic traits between LDM and PMM. For example, the hyper-methylation and down-regulation of HK-2 and PFKFB4 were related to decrease glycolytic potential in PMM. In addition, promoter hypo-methylation and the up-regulation of miR-378 silenced the expression of the target genes and promoted capillary biosynthesis in PMM. Together, these results improve understanding of muscle metabolism and development from genomic and epigenetic perspectives. PMID- 27561203 TI - Selection and validation of reliable reference genes for RT-qPCR analysis in a large cohort of pituitary adenomas. AB - BACKGROUND: Real-time reverse transcription quantitative PCR (RT-qPCR) has become the method of choice for quantification of gene expression changes. The most important limitations of RT-qPCR are inappropriate data normalization and inconsistent data analyses. Pituitary adenomas are common tumours, and the appropriate interpretation of increasingly published data within this field is prevented by the lack of a proper selection and validation of stably expressed reference genes. AIM: To find and validate the optimal reference gene or gene combination for reliable RT-qPCR gene expression in both non-functioning (NFPA) and hormone secreting (GH and ACTH) pituitary adenomas. MATERIAL AND METHODS: Thirty commonly used reference genes (PCR array reference gene panel, BioRad, Hercules, CA) were quantified by RT-qPCR in 24 pituitary adenomas (12 NFPA, 8 GH and 4 ACTH). The data was analysed using three programs: geNorm (Qbase+), Normfinder and BestKeeper having different algorithms to identify the most stable reference gene or combination of reference genes. Three reference genes ALAS1, PSMC4 and GAPDH, were selected for further validation in a larger cohort of 223 adenomas (141 NFPA, 63 GH and 19 ACTH). RESULTS: In all adenomas, ALAS1 and PSMC4 were the most stable reference genes as estimated by geNorm and Normfinder, whereas Bestkeeper ranked RPLP0 and ACTB as the two most stable out of 10 carefully selected genes. The best gene combination was PSMC4 and ALAS1 (geNorm) or PSMC4 and GAPDH (Normfinder). The validation experiment (geNorm) showed that the most stable gene combinations were ALAS1 and GAPDH in NFPA, and PSMC4 and GAPDH in hormone secreting adenomas. CONCLUSIONS: Several of the reference genes expressed good stability yielding several candidate genes. PSMC4 and ALAS1 were overall the most stably expressed genes in pituitary adenoma merely differing in ranking order. PSMC4 and ALAS1 have so far not been reported as reference genes in pituitary adenomas. The various reference gene algorithms showed a mixed selection of top ranked genes, thus suggesting a need for an individualised and rational choice of reference genes. PMID- 27561202 TI - Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. AB - The hormone - specific FSHbeta subunit of the human FSH heterodimer consists of N linked glycans at Asn7 and Asn24 residues that are co-translationally attached early during subunit biosynthesis. Differences in the number of N-glycans (none, one or two) on the human FSHbeta subunit contribute to macroheterogeneity in the FSH heterodimer. The resulting FSH glycoforms are termed hypo-glycosylated (FSH21/18, missing either an Asn24 or Asn7 N-glycan chain on the beta - subunit, respectively) or fully glycosylated (FSH24, possessing of both Asn7 and Asn24 N linked glycans on the beta - subunit) FSH. The recombinant versions of human FSH glycoforms (FSH21/18 and FSH24) have been purified and biochemically characterized. In vitro functional studies have indicated that FSH21/18 exhibits faster FSH- receptor binding kinetics and is much more active than FSH24 in every assay tested to date. However, the in vivo bioactivity of the hypo-glycosylated FSH glycoform has never been tested. Here, we evaluated the in vivo bioactivities of FSH glycoforms in Fshb null mice using a pharmacological rescue approach. In Fshb null female mice, both hypo- and fully-glycosylated FSH elicited an ovarian weight gain response by 48 h and induced ovarian genes in a dose- and time dependent manner. Quantification by real time qPCR assays indicated that hypo glycosylated FSH21/18 was bioactive in vivo and induced FSH-responsive ovarian genes similar to fully-glycosylated FSH24. Western blot analyses followed by densitometry of key signaling components downstream of the FSH-receptor confirmed that the hypo-glycosylated FSH21/18 elicited a response similar to that by fully glycosylated FSH24 in ovaries of Fshb null mice. When injected into Fshb null males, hypo-glycosylated FSH21/18 was more active than the fully-glycosylated FSH24 in inducing FSH-responsive genes and Sertoli cell proliferation. Thus, our data establish that recombinant hypo-glycosylated human FSH21/18 glycoform elicits bioactivity in vivo similar to the fully-glycosylated FSH. Our studies may have clinical implications particularly in formulating FSH-based ovarian follicle induction protocols using a combination of different human FSH glycoforms. PMID- 27561204 TI - Autosomal dominant hypocalcemia due to a truncation in the C-tail of the calcium sensing receptor. AB - Autosomal Dominant Hypocalcemia (ADH) is an endocrine disorder due to activating mutations of the calcium-sensing receptor (CASR) gene. We report on a young boy who presented low serum calcium with hypercalciuria, hyperphosphatemia and low serum concentration of parathyroid hormone, not accompanied by classic clinical signs of hypocalcemia. Treatment with calcitriol and calcium did not normalize serum calcium and renal calcium excretion. The use of thiazide diuretics slightly reduced calciuria. Despite high calcium excretion, no signs of nephrocalcinosis were detected. The patient had a prolonged Q-T interval at ECG, which did not normalize during treatment. PCR amplification of CASR coding sequence and direct sequencing of PCR products. showed a novel heterozygous deletion of a cytosine (c.2682delC), responsible for a frameshift (p.S895Pfs*44) and a premature stop codon resulting in a truncation of the CaSR's C-tail. Functional studies indicated increased activity of mutant receptor compared to the wild-type. PMID- 27561206 TI - Cervical dilation at time of caesarean delivery in nulliparous women: a population-based cohort study. AB - OBJECTIVES: Our objective was to describe contemporary practice patterns in the timing of caesarean delivery in relation to cervical dilation, overall and by indication for caesarean. Our secondary objective was to examine how commonly caesarean delivery was performed for labour dystocia at dilations below 4 cm or without the use of oxytocin, overall and between hospitals. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Alberta, and British Columbia, Canada, 2008-2012. POPULATION: Nulliparous women in labour who delivered term singletons in cephalic position. METHODS: Histograms were used to examine the distribution of cervical dilation at time of caesarean delivery, overall and by indication for caesarean. Funnel plots were used to illustrate variation in hospital-level rates of caesarean deliveries for labour dystocia that were performed early (<4 cm dilation) or without the use of oxytocin. MAIN OUTCOME MEASURES: Cervical dilation (in centimetres) at time of caesarean delivery. RESULTS: The population-based cohort comprised 392 025 women, of whom 18.8% had a caesarean delivery. Of first-stage caesareans for labour dystocia in women who entered labour spontaneously, 13.6% (95% CI 12.9, 14.2) had dilations <4 cm [hospital-level inter-quartile range (IQR): 6.2% to 20.0%] and 29.5% (95% CI 28.6, 30.4) did not receive oxytocin to treat their dystocia (hospital-level IQR: 22.1-54.6%). CONCLUSIONS: The proportion of caesareans done before 4 cm dilation or without oxytocin varies substantially across hospitals and suggests the need for institutions to review their practices and ensure that management of labour practice guidelines are followed. TWEETABLE ABSTRACT: Many caesareans for labour dystocia are performed early during labour (<4 cm dilation) or without oxytocin. PMID- 27561205 TI - The small noncoding RNAs (sncRNAs) of murine gammaherpesvirus 68 (MHV-68) are involved in regulating the latent-to-lytic switch in vivo. AB - The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV), which are associated with a variety of diseases including tumors, produce various small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs). Like all herpesviruses, they show two stages in their life cycle: lytic replication and latency. During latency, hardly any viral proteins are expressed to avoid recognition by the immune system. Thus, sncRNAs might be exploited since they are less likely to be recognized. Specifically, it has been proposed that sncRNAs might contribute to the maintenance of latency. This has already been shown in vitro, but the respective evidence in vivo is very limited. A natural model system to explore this question in vivo is infection of mice with murine gammaherpesvirus 68 (MHV-68). We used this model to analyze a MHV-68 mutant lacking the expression of all miRNAs. In the absence of the miRNAs, we observed a higher viral genomic load during late latency in the spleens of mice. We propose that this is due to a disturbed regulation of the latent-to-lytic switch, altering the balance between latent and lytic infection. Hence, we provide for the first time evidence that gammaherpesvirus sncRNAs contribute to the maintenance of latency in vivo. PMID- 27561207 TI - Pseudogenes regulate parental gene expression via ceRNA network. AB - The concept of competitive endogenous RNA (ceRNA) was first proposed by Salmena and colleagues. Evidence suggests that pseudogene RNAs can act as a 'sponge' through competitive binding of common miRNA, releasing or attenuating repression through sequestering miRNAs away from parental mRNA. In theory, ceRNAs refer to all transcripts such as mRNA, tRNA, rRNA, long non-coding RNA, pseudogene RNA and circular RNA, because all of them may become the targets of miRNA depending on spatiotemporal situation. As binding of miRNA to the target RNA is not 100% complementary, it is possible that one miRNA can bind to multiple target RNAs and vice versa. All RNAs crosstalk through competitively binding to miRNAvia miRNA response elements (MREs) contained within the RNA sequences, thus forming a complex regulatory network. The ratio of a subset of miRNAs to the corresponding number of MREs determines repression strength on a given mRNA translation or stability. An increase in pseudogene RNA level can sequester miRNA and release repression on the parental gene, leading to an increase in parental gene expression. A massive number of transcripts constitute a complicated network that regulates each other through this proposed mechanism, though some regulatory significance may be mild or even undetectable. It is possible that the regulation of gene and pseudogene expression occurring in this manor involves all RNAs bearing common MREs. In this review, we will primarily discuss how pseudogene transcripts regulate expression of parental genes via ceRNA network and biological significance of regulation. PMID- 27561208 TI - GnRH and prostaglandin-based synchronization protocols as alternatives to progestogen-based treatments in sheep. AB - The study investigated, for cycling sheep, synchronizing protocols simultaneously to the standard "P" protocol using progestogens priming with intravaginal devices and gonadotropin. In November 2014, 90 adult Menz ewes were assigned to either the "P" protocol, "PGF" treatment where oestrus and ovulation were synchronized using two injections of prostaglandin 11 days apart or a "GnRH" treatment where the ewes had their oestrus and ovulation synchronized with GnRH (day 0) prostaglandin (day 6)-GnRH (day 9) sequence. The ewes were naturally mated at the induced oestrus and the following 36 days. Plasma progesterone revealed that 92% of the ewes were ovulating before synchronization and all, except one, ovulated in response to the applied treatments. All "P" ewes exhibited oestrus during the 96-hr period after the end of the treatments in comparison with only 79.3% and 73.3% for "PGF" and "GnRH" ewes, respectively (p < .05). Onset and duration of oestrus were affected by the hormonal treatment (p < .05); "GnRH" ewes showed oestrus earliest and had the shortest oestrous duration. Lambing rate from mating at the induced oestrus was lower for "P" than for "PGF" ewes (55.6% and 79.3%, respectively; p < .05). The same trait was also lower for "P" than for "PGF" and "GnRH" ewes (70.4%, 89.7% and 86.7%, respectively; p < .05) following the 36-day mating period. Prostaglandin and GnRH analogue-based protocols are promising alternatives for both controlled natural mating and fixed insemination of Menz sheep after the rainy season when most animals are spontaneously cycling. PMID- 27561209 TI - Species-specific responses to climate change and community composition determine future calcification rates of Florida Keys reefs. AB - Anthropogenic climate change compromises reef growth as a result of increasing temperatures and ocean acidification. Scleractinian corals vary in their sensitivity to these variables, suggesting species composition will influence how reef communities respond to future climate change. Because data are lacking for many species, most studies that model future reef growth rely on uniform scleractinian calcification sensitivities to temperature and ocean acidification. To address this knowledge gap, calcification of twelve common and understudied Caribbean coral species was measured for two months under crossed temperatures (27, 30.3 degrees C) and CO2 partial pressures (pCO2 ) (400, 900, 1300 MUatm). Mixed-effects models of calcification for each species were then used to project community-level scleractinian calcification using Florida Keys reef composition data and IPCC AR5 ensemble climate model data. Three of the four most abundant species, Orbicella faveolata, Montastraea cavernosa, and Porites astreoides, had negative calcification responses to both elevated temperature and pCO2 . In the business-as-usual CO2 emissions scenario, reefs with high abundances of these species had projected end-of-century declines in scleractinian calcification of >50% relative to present-day rates. Siderastrea siderea, the other most common species, was insensitive to both temperature and pCO2 within the levels tested here. Reefs dominated by this species had the most stable end-of-century growth. Under more optimistic scenarios of reduced CO2 emissions, calcification rates throughout the Florida Keys declined <20% by 2100. Under the most extreme emissions scenario, projected declines were highly variable among reefs, ranging 10-100%. Without considering bleaching, reef growth will likely decline on most reefs, especially where resistant species like S. siderea are not already dominant. This study demonstrates how species composition influences reef community responses to climate change and how reduced CO2 emissions can limit future declines in reef calcification. PMID- 27561211 TI - Incidence of Bisphosphonate Use in Relation to Diagnosis of Alzheimer's Disease in Community-Dwelling Persons. PMID- 27561210 TI - Subjective and objective outcome measures after total knee replacement: is there a correlation? AB - BACKGROUND: Although various methods for quantifying outcomes following total knee replacement (TKR) are used, there are few studies of the relationships between patient reported scores and functional tests. This paper aims to assess the relationships between commonly used outcome scores after TKR through a prospective cohort study. METHODS: Twenty-four patients who had undergone unilateral TKR were assessed using four patient-reported outcome scores as well as objective measurements of knee laxity, quadriceps muscle strength and the Timed Up and Go Test. All scores and measures were correlated using the Pearson product moment correlation coefficient using the lower one-sided 95% confidence interval. A level of significance of P < 0.05 was selected. RESULTS: The Timed Up and Go Test was the only objective measure to demonstrate a statistically significant correlation (r = -0.557 to -0.770, P = 0.0001-0.005) with patient reported scores. CONCLUSION: A comprehensive assessment of outcomes after TKR requires both subjective and objective assessments. Walking ability and speed are important to the TKR patient and are representative of their pain and function. PMID- 27561212 TI - Rational Design of Zirconium-doped Titania Photocatalysts with Synergistic Bronsted Acidity and Photoactivity. AB - The preparation of photocatalysts with high activities under visible-light illumination is challenging. We report the rational design and construction of a zirconium-doped anatase catalyst (S-Zr-TiO2 ) with Bronsted acidity and photoactivity as an efficient catalyst for the degradation of phenol under visible light. Electron microscopy images demonstrate that the zirconium sites are uniformly distributed on the sub-10 nm anatase crystals. UV-visible spectrometry indicates that the S-Zr-TiO2 is a visible-light-responsive catalyst with narrower band gap than conventional anatase. Pyridine-adsorption infrared and acetone-adsorption 13 C NMR spectra confirm the presence of Bronsted acidic sites on the S-Zr-TiO2 sample. Interestingly, the S-Zr-TiO2 catalyst exhibits high catalytic activity in the degradation of phenol under visible-light illumination, owing to a synergistic effect of the Bronsted acidity and photoactivity. Importantly, the S-Zr-TiO2 shows good recyclability. PMID- 27561213 TI - Expression of segment polarity genes in brachiopods supports a non-segmental ancestral role of engrailed for bilaterians. AB - The diverse and complex developmental mechanisms of segmentation have been more thoroughly studied in arthropods, vertebrates and annelids-distantly related animals considered to be segmented. Far less is known about the role of "segmentation genes" in organisms that lack a segmented body. Here we investigate the expression of the arthropod segment polarity genes engrailed, wnt1 and hedgehog in the development of brachiopods-marine invertebrates without a subdivided trunk but closely related to the segmented annelids. We found that a stripe of engrailed expression demarcates the ectodermal boundary that delimits the anterior region of Terebratalia transversa and Novocrania anomala embryos. In T. transversa, this engrailed domain is abutted by a stripe of wnt1 expression in a pattern similar to the parasegment boundaries of insects-except for the expression of hedgehog, which is restricted to endodermal tissues of the brachiopod embryos. We found that pax6 and pax2/5/8, putative regulators of engrailed, also demarcate the anterior boundary in the two species, indicating these genes might be involved in the anterior patterning of brachiopod larvae. In a comparative phylogenetic context, these findings suggest that bilaterians might share an ancestral, non-segmental domain of engrailed expression during early embryogenesis. PMID- 27561214 TI - Commentary: IL-17 in Chronic Inflammation: From Discovery to Targeting. PMID- 27561215 TI - Mosapride for gastroesophageal reflux disease in neurologically impaired patients. AB - BACKGROUND: The prokinetic agent cisapride is effective for the treatment of gastroesophageal reflux disease (GERD) in infants and children, but is no longer used for this purpose because of safety concerns. Therefore, other pharmacological agents need to be investigated for efficacy in GERD treatment. In this study, we examined the effectiveness and safety of mosapride for the treatment of neurologically impaired children and adolescents with GERD. METHODS: Mosapride (0.3 mg/kg/day) was administered to 11 neurologically impaired patients with GERD (five male; median age, 12.3 years). Esophageal acid exposure was measured using esophageal pH monitoring before and at >5 days after the start of mosapride treatment. The pressure and length of the lower esophageal sphincter were compared before and after mosapride treatment. RESULTS: In the 11 patients, median reflux index (percentage of the total monitoring period during which recorded pH was <4.0) was 17.5% (range, 4.4-59%) before and 8.2% (range, 2.8 20.7%) after mosapride treatment (P = 0.02). Median esophageal clearance was 1.0 min/reflux (range, 0.5-2.1 min/reflux) before and 0.7 min/reflux (range, 0.4-1.2 min/reflux) after treatment with mosapride (P = 0.02). The median number of reflux episodes before (219) and after (122) drug treatment did not differ significantly. CONCLUSION: The decreased reflux index in neurologically impaired patients with GERD is due to mosapride, therefore mosapride may be a candidate for GERD treatment. PMID- 27561216 TI - Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater. AB - Rapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory. PMID- 27561218 TI - A framework for modeling human evolution. AB - Culture-led gene-culture coevolution is a framework within which substantive explanations of human evolution must be located. It is not itself an explanation. Explanations depend on such concrete historical evolutionary factors such as the control of fire, collective child-rearing, lethal weapon technology, altruistic cooperation and punishment, and the mastery of complex collaboration protocols leading to an effective division of social labor. PMID- 27561217 TI - Executive function and academic achievement in primary - grade students with Down syndrome. AB - BACKGROUND: Executive function (EF) plays a critical role in academic outcomes in typically developing children, but the contribution of EF to academic performance in Down syndrome (DS) is less well understood. This study evaluated differences in early academic foundations between primary school aged children with DS and non-verbal mental-age matched typically developing (TD) children. Additionally, the contribution of EF domains to academic outcomes was evaluated in each group. METHOD: Participants with DS (n = 29) and mental-age matched TD participants (n = 23) were administered the Woodcock Johnson- III NU Tests of Academic Achievement, as well as a laboratory-based EF battery, including measures of working memory, shifting, inhibition and object-planning. RESULTS: Findings indicated a difference in early academic foundations profile between children with DS and mental-age matched TD children. Patterns of EF contributions towards academic outcomes were also observed across groups. CONCLUSIONS: Aspects of EF are critical to academic achievement in DS but differentially so relative to typical development. Implications for educational instruction are discussed. PMID- 27561219 TI - Is Now-or-Never language processing good enough? AB - Christiansen & Chater's (C&C's) Now-or-Never bottleneck framework is similar to the Good-Enough Language Processing model (Ferreira et al. 2002), particularly in its emphasis on sparse representations. We discuss areas of overlap and review experimental findings that reinforce some of C&C's arguments, including evidence for underspecification and for parsing in "chunks." In contrast to Good-Enough, however, Now-or-Never does not appear to capture misinterpretations or task effects, both of which are important aspects of comprehension performance. PMID- 27561221 TI - Ethical Issues and Practical Challenges in Suicide Research. AB - BACKGROUND: Research with human subjects represents a critical avenue for suicide prevention efforts; however, such research is not without its ethical and practical challenges. Specifically, given the nature of research with individuals at elevated risk for suicide (e.g., increased concerns regarding participant safety, adverse events, liability, difficulties often arise during the institutional review board (IRB) evaluation and approval process. AIMS: This paper aims to discuss IRB-related issues associated with suicide prevention research, including researcher and IRB panel member responsibilities, suicide risk assessment and management ethics and procedures, informed consent considerations, preparation of study protocols, and education and training. Points to consider and components to potentially include in an IRB application for suicide-related research are additionally provided. METHOD: Literature relevant to ethics in suicide research and suicide risk assessment and management was reviewed and synthesized. RESULTS: Suicide research can be conducted in accordance with ethical principles while also furthering the science of suicide prevention. CONCLUSION: Despite the challenging nature of suicide prevention research, empirically informed solutions exist to address difficulties that may emerge in interfacing with IRBs. There remain areas for improvement in the IRB approval process that warrant further investigation and work. PMID- 27561220 TI - Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study. AB - The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL. PMID- 27561222 TI - Correction to Till et al., 2016. PMID- 27561223 TI - Outcomes of a Suicide Prevention Gatekeeper Training Program Among School Personnel. AB - BACKGROUND: Gatekeeper suicide prevention programs train staff to increase the identification and referral of suicidal individuals to the appropriate resources. AIMS: We evaluated Act on FACTS: Making Educators Partners in Youth Suicide Prevention (MEP), which is an online training program designed to enhance the knowledge of suicide risk factors and warning signs as well as improve participants' attitudes and self-efficacy/confidence. METHOD: School personnel (N = 700) completed a survey administered before and immediately after the training to assess gains in training outcomes and to evaluate participants' satisfaction with the training. RESULTS: Results indicated that MEP participants demonstrated significant increases in suicide knowledge, attitudes, and self-efficacy. Moreover, exploratory analyses revealed moderating effects of professional role on pre-/posttest changes in self-efficacy, but not suicide knowledge or attitudes. Specifically, guidance counselors demonstrated significantly smaller increases in self-efficacy/confidence compared with teachers and classroom aids, whereas teachers demonstrated significantly larger increases in self efficacy/confidence compared with administrators. The majority of school personnel who completed the MEP program were satisfied with the training content and experience. CONCLUSION: Although the current findings are promising, more rigorous evaluations employing randomized controlled research designs are warranted to adequately determine the effectiveness of the MEP program. PMID- 27561224 TI - Stakeholder Perspectives on the Stigma of Suicide Attempt Survivors. AB - BACKGROUND: Past scholarly efforts to describe and measure the stigma surrounding suicide have largely viewed suicide stigma from the perspective of the general public. AIMS: In the spirit of community-based participatory research (CBPR), the current study brought together a diverse stakeholder team to qualitatively investigate the suicide stigma as experienced by those most intimately affected by suicide. METHOD: Seven focus groups (n = 62) were conducted with suicide attempt survivors, family members of those who died by suicide, and suicide loss therapists. RESULTS: Themes were derived for stereotypes (n = 30), prejudice (n = 3), and discrimination (n = 4). People who attempted suicide were seen as attention-seeking, selfish, incompetent, emotionally weak, and immoral. Participants described personal experiences of prejudice and discrimination, including those with health professionals. CONCLUSION: Participants experienced public stigma, self-stigma, and label avoidance. Analyses reveal that the stigma of suicide shares similarities with stereotypes of mental illness, but also includes some important differences. Attempt survivors may be subject to double stigma, which impedes recovery and access to care. PMID- 27561225 TI - Promoting Help Seeking to Veterans. AB - BACKGROUND: Few studies have considered different messaging strategies that may augment campaign efficacy to generate help-seeking behaviors among populations at increased risk for suicide, mainly US military veterans. AIMS: Findings are presented from the pilot evaluation of the It's Your Call campaign implemented by the Department of Veterans Affairs (VA). Three messaging strategies (with varying intensity and mix of messages) were compared to explore which best promote use of the Veterans Crisis Line (VCL) among veteran populations. METHOD: Daily VCL call data were obtained for 10 US cities during 2011-2012 where the campaign was active, and modeled using Poisson regression to identify changes in utilization patterns associated with the implementation of different messaging strategies. RESULTS: Significant increases in call rates were only evident during the campaign in communities where mixed messages were disseminated. Further, use of mixed messages yielded greater increases in call rates when compared with the other tested strategies. This was an observational study where identification of causal relationships between variables was limited. CONCLUSION: Findings are encouraging as messaging was associated with help seeking, and they provide insights into strategies that may rapidly promote crisis line use. Results also underscore the need for further research on suicide prevention campaigns and dissemination practices. PMID- 27561226 TI - The Role of Positive Expectancies in Risk Behavior. AB - BACKGROUND: Alcohol use and nonsuicidal self-injury (NSSI) appear to share a conceptual overlap in functions (e.g., tension reduction). Alcohol use has been identified as a risk factor for NSSI, and higher rates of alcohol use have been documented among those with NSSI history. AIMS: This study examined whether NSSI related alcohol expectancies affect relations between NSSI and alcohol use. METHOD: Participants were 367 college students (73% female) asked to complete an online survey about their drinking behavior and lifetime NSSI. RESULTS: NSSI and alcohol use were highly prevalent in this sample: 56% endorsed lifetime NSSI and 74% endorsed current alcohol use. Of note, 43% (n = 147) endorsed both behaviors. Positive NSSI-related alcohol expectancies showed a significant association with lifetime NSSI. In addition, positive NSSI-related alcohol expectancies were associated with more frequent drinking behavior for individuals with a history of NSSI, particularly those who had engaged in two or more methods of lifetime NSSI. CONCLUSION: Alcohol use and NSSI represent high-risk behaviors commonly employed to regulate unwanted affective states. Interventions targeting substance use and/or NSSI may consider assessing positive NSSI and substance use expectancies, as the presence of these beliefs suggests a higher risk profile. PMID- 27561227 TI - Seasonal programming, not competition or testosterone, drives stress-axis changes in a partially-semelparous mammal. AB - Animals must make tradeoffs between reproduction and longevity. This is particularly pronounced in male arctic ground squirrels (Urocitellus parryii), that compete aggressively for territories and mates during a three-week breeding season. Breeding males have high rates of severe wounding, high mortality rates, and high free cortisol levels, along with downstream consequences of chronic stress (weight loss, reduced immune function) that appear to contribute to their early death. The elevated cortisol levels are thought to be a result of the intense intrasexual competition. An alternative hypothesis, however, is that the hormonal change is a seasonal adaptation facilitating the tradeoff of immediate competitive advantage at the expense of long-term survival. We tested a two-part hypothesis: first, that elevated free cortisol during the breeding period is a seasonal change that will still occur in the absence of actual competition, and second, that testosterone maintains this increase. We measured plasma cortisol, corticosteroid-binding globulin, and fecal glucocorticoid metabolites in three groups: wild male ground squirrels, captive males prevented from fighting, and captive castrated males. There were no differences amongst these three groups in free and total plasma cortisol, fecal glucocorticoids, or downstream measures of chronic stress. This suggests that high free cortisol and its effects on breeding males are not a consequence of contest competition during the breeding season, but rather a generalized seasonal change. We found no evidence that testosterone plays a role in maintaining elevated free cortisol in arctic ground squirrel males. PMID- 27561228 TI - Theoretical Study of the Charge-Transfer State Separation within Marcus Theory: The C60-Anthracene Case Study. AB - We study, within Marcus theory, the possibility of the charge-transfer (CT) state splitting at organic interfaces and a subsequent transport of the free charge carriers to the electrodes. As a case study we analyze model anthracene-C60 interfaces. Kinetic Monte Carlo (KMC) simulations on the cold CT state were performed at a range of applied electric fields, and with the fields applied at a range of angles to the interface to simulate the action of the electric field in a bulk heterojunction (BHJ) interface. The results show that the inclusion of polarization in our model increases CT state dissociation and charge collection. The effect of the electric field on CT state splitting and free charge carrier conduction is analyzed in detail with and without polarization. Also, depending on the relative orientation of the anthracene and C60 molecules at the interface, CT state splitting shows different behavior with respect to both applied field strength and applied field angle. The importance of the hot CT in helping the charge carrier dissociation is also analyzed in our scheme. PMID- 27561229 TI - Cultural group selection is plausible, but the predictions of its hypotheses should be tested with real-world data. AB - The evidence compiled in the target article demonstrates that the assumptions of cultural group selection (CGS) theory are often met, and it is therefore a useful framework for generating plausible hypotheses. However, more can be said about how we can test the predictions of CGS hypotheses against competing explanations using historical, archaeological, and anthropological data. PMID- 27561230 TI - The influence of proprioception on reading performance. AB - BACKGROUND: Visual ergonomics has an impact on visual performance in reading. Based on the assumption that reading from an LCD screen held in the hands provides more accurate information about the distance to the object than reading from a screen, which has no contact with our body, this study assessed the influence of the proprioceptive input on the speed of reading and on accommodative and pupillary responses and their micro-oscillations. METHODS: Participants (n = 47; all emmetropic, non-amblyopic), were asked to read in their minds two-digit numerals presented on a 10-inch LCD screen at 40 cm distance. In one condition, the participants held the screen in their hands; in the other, the screen was placed on the holder and there was no body contact with the participant. The number of numerals read in 90 seconds was recorded. Accommodative and pupillary responses were measured with Power Refractor 3 at a 50 Hz measurement rate. RESULTS: The number of numerals read was greater for the condition with proprioceptive input than in the condition without contact. The mean pupil size and the average accommodative response were similar in the two conditions. The rate of change in pupil size showed a steeper decline in the condition without the proprioceptive input compared to the condition with this input. The increase in the lag of accommodation with time was similar in both conditions, as well as pupillary and accommodative micro-oscillations. CONCLUSIONS: When the screen was held in the hands, reading of numerals was faster and resulted in less pupil size change over the 90-second test interval. This indicates that proprioception might influence some aspects of visual performance. PMID- 27561231 TI - Reprint of "Attitudes towards honey among Italian consumers: A choice experiment approach". AB - Honey is becoming increasingly popular with consumers for its nutritional benefits as well as many other functions. The objective of this article is to determine which factors influence consumers' purchase intentions and to assess the importance of certain honey characteristics to enable identification of the constituents of an ideal honey profile. This information will lead to satisfaction of consumers' preferences and formulation of marketing strategies that support honey makers. We applied a choice experiment to the Italian honey market to define the preferences and the willingness to pay for key characteristics of the product. A face-to-face questionnaire survey was conducted in 2014 (January-July) among Italian consumers; it was completed by 427 respondents. A latent class model was estimated and four classes were identified, with different preferences, illustrating that respondents seem to be heterogeneous honey consumers. Results suggest the "organic" attribute was more important than others factors, such as the place where the honey was produced (landscape), but less important than the country of origin; local Italian honey was preferred to foreign honey. Respondents showed a higher willingness to pay (WTP) for honey from their country of origin versus the production method used. Our results suggest that while organic beekeeping might be an important strategy for diversification, if suitable communication is not taken into consideration, the added value of the production method might not be perceived by consumers. PMID- 27561232 TI - Concentrated Phosphatidic Acid in Cereal Brans as Potential Protective Agents against Indomethacin-Induced Stomach Ulcer. AB - One of complications associated with long-term use of nonsteroidal anti inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer. PMID- 27561233 TI - Nano-based rescue of dysfunctional autophagy in chronic obstructive lung diseases. AB - INTRODUCTION: DeltaF508-CFTR (cystic fibrosis transmembrane conductance regulator) is a common CF-mutation that is known to induce oxidative-inflammatory stress through activation of reactive oxygen species (ROS), which induces autophagy-impairment resulting in accumulation of CFTR in aggresome-bodies. Cysteamine, the reduced form of cystamine, is a FDA-approved drug that has anti oxidant, anti-bacterial, and mucolytic properties. This drug has been shown in a recent clinical trial to decrease lung inflammation and improve lung function in CF patients by potentially restoring autophagy and allowing CFTR to be trafficked to the cell membrane. Areas covered: The delivery of cysteamine to airway epithelia of chronic subjects prerequisite the need for a delivery system to allow rescue of dysfunctional autophagy. Expert opinion: We anticipate based on our ongoing studies that PLGA-PEG- or Dendrimer-mediated cysteamine delivery could allow sustained airway delivery over standard cysteamine tablets or delay release capsules that are currently used for systemic treatment. In addition, proposed nano-based autophagy induction strategy can also allow rescue of cigarette smoke (CS) induced acquired-CFTR dysfunction seen in chronic obstructive pulmonary disease (COPD)-emphysema subjects. The CS induced acquired CFTR dysfunction involves CFTR-accumulation in aggresome-bodies that can be rescued by an autophagy-inducing antioxidant drug, cysteamine. Moreover, chronic CS-exposure generates ROS that induces overall protein-misfolding and aggregation of ubiquitinated-proteins as aggresome-bodies via autophagy-impairment that can be also be resolved by treatment with autophagy-inducing antioxidant drug, cysteamine. PMID- 27561234 TI - Neural reuse leads to associative connections between concrete (physical) and abstract (social) concepts and motives. AB - Consistent with neural reuse theory, empirical tests of the related "scaffolding" principle of abstract concept development show that higher-level concepts "reuse" and are built upon fundamental motives such as survival, safety, and consumption. This produces mutual influence between the two levels, with far-ranging impacts from consumer behavior to political attitudes. PMID- 27561235 TI - Impact of dietary fibre:starch ratio in shaping caecal archaea revealed in rabbits. AB - In rabbits, many studies have investigated the effect of diet, including the fibre intake, on caecal microbiota; however, there are no direct measurements of the influence of diets with different dietary fibre-to-starch ratios and the archaeal community composition in the caecum. We used 16S rDNA sequencing to investigate the impact of different dietary neutral detergent fibre (NDF)-to starch ratios (1.0-2.3) on the caecal archaeal community in rabbits. The results revealed that the archaeal community from all experimental rabbits was relatively less complex than intestinal bacterial community. High-throughput 16S rDNA sequencing of the gut archaea indicated that the rabbit caecum was inhabited by Methanobrevibacter and Methanosphaera species, and therefore is possibly dominated by two species of archaea. Here, we compared the effect of different diets on the archaeal community in the rabbit caecum and found no significant differences in the diversity and abundance of caecal archaeal community of rabbits that were fed diets with different dietary fibre-to-starch ratios. Therefore, we suggest that the contribution of host-derived substrates to caecal archaea constitution is insignificant. PMID- 27561236 TI - Influence of chemical ordering on the thermal conductivity and electronic relaxation in FePt thin films in heat assisted magnetic recording applications. AB - We report on the out-of-plane thermal conductivities of tetragonal L10 FePt (001) easy-axis and cubic A1 FePt thin films via time-domain thermoreflectance over a temperature range from 133 K to 500 K. The out-of-plane thermal conductivity of the chemically ordered L10 phase with alternating Fe and Pt layers is ~23% greater than the thermal conductivity of the disordered A1 phase at room temperature and below. However, as temperature is increased above room temperature, the thermal conductivities of the two phases begin to converge. Molecular dynamics simulations on model FePt structures support our experimental findings and help shed more light into the relative vibrational thermal transport properties of the L10 and A1 phases. Furthermore, unlike the varying temperature trends in the thermal conductivities of the two phases, the electronic scattering rates in the out-of-plane direction of the two phases are similar for the temperature range studied in this work. PMID- 27561238 TI - T cell repertoire following kidney transplantation revealed by high-throughput sequencing. AB - Delayed T cell recovery and restricted T cell receptor (TCR) diversity after kidney transplantation are associated with increased risks of infection and malignancy. Technical challenges limit the faithful measurement of TCR diversity after kidney transplantation. In this study, we used a combination of multiplex PCR, Illumina sequencing and IMGT/HighV-QUEST to directly assess millions of TCRs per individual before and at two time points after kidney transplantation (1days and 7days after transplantation) in a cohort of 10 patients compared to a normal control (NC) group (n=10). We identified the most commonly observed CDR3 length, VD indel length, and DJ indel length in transplantation group and normal group. In addition, we found that the TCR repertoire diversity of transplantation groups was relatively lower compared to NC group. T cell depletion in Post-1 group can be observed, which resulted in the altered distribution characteristics of clonotype abundance. A modest proportion of high abundance clones were shared among the pre-1 group, post-1 group and post-7 group, and it did not exist in the NC group, which exhibited a signature of antigen selection. Moreover, our results also demonstrated that various TRBV expression increased and some public sequences at different time points after kidney transplantation, which may provide biomarkers to monitor the immune status of transplant patients. PMID- 27561237 TI - Lymphodepletive effects of rabbit anti-pig thymocyte globulin in neonatal swines. AB - Lymphodepletive agents play important role in different clinical applications or experimental transplant studies. In order to facilitate preclinical pediatric transplant studies, we have developed the rabbit anti-pig thymocyte globulin (pATG) and studied its effects in neonatal swines. In vitro assays showed that pATG can bind to lymphocytes and neutrophils in a dose-dependent manner and lyse peripheral blood mononuclear cells by apoptosis and complement-dependent cytotoxicity. In vivo, pATG as a monotherapy was administered at different doses (2.5, 5, 20, 40 and 80mg/kg) in newborn pigs. Results showed that pATG induced a dose-dependent but transient T-cell depletion in peripheral blood. Lymphodepletion was also observed in lymph nodes, spleen and thymus. Pharmacokinetic studies showed dose-related cell-bound pATG on lymphocytes, as well as the presence of free pATG in the serum. Both cell-bound and free pATG levels decreased gradually after administration. Interestingly, adjuvant mycophenolate mofetil (MMF) given at 1g/m2/day for 1week successfully maintained pATG-induced T-cell depletion. In conclusion, pATG administration can cause transient T-cell depletion in neonatal pigs and this effect can be maintained by MMF. Therefore, we have developed an original immunosuppressive regimen that can be used for transplantation studies in swine model. PMID- 27561239 TI - Humoral immunity in phenotypes of chronic lung allograft dysfunction: A broncho alveolar lavage fluid analysis. AB - BACKGROUND: Recently, antibody mediated rejection (AMR) has been associated with a higher incidence of chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation (LTx). We investigated markers related to AMR and matrix remodeling in CLAD, with special attention for its two phenotypes being bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD). METHODS: Immunoglobulins (IgA, IgE, IgG1-IgG4, total IgG and IgM) and complement (C4d and C1q) were quantified in lung lavage samples at the moment of BOS (n=15) or RAS (n=16) diagnosis; and were compared to stable transplant patients who served as control (n=14). Also, airway remodeling and metalloproteinases (MMPs) were investigated via zymography and gelatin degradation. The presence of DSA was additionally assessed in blood. RESULTS: Total IgG, IgG1-IgG4 and IgM were increased in rCLAD versus control (p<0.001) and BOS patients (p<0.01). IgA and IgE were increased in rCLAD compared to control (respectively p<0.05 and p<0.01), but not to BOS. Total IgG and IgE were increased in BOS versus control (respectively p<0.01 and p<0.05). Complement proteins were exclusively present in rCLAD and correlated positively with immunoglobulins. Additionally, in blood, DSA were more present in rCLAD (p=0.041). MMP-9 levels increased in RAS and BOS versus control (p<0.001) and MMP-9 induced gelatin degradation was only increased in BOS compared to control (p<0.01). CONCLUSION: We demonstrated increased levels of immunoglobulins and complement proteins dominantly present in rCLAD. This leads to the belief that antibodies and AMR might play a more important role in rCLAD compared to BOS. Therefore, anti B-cell therapy could offer beneficial therapeutic effects in patients diagnosed with rCLAD, which needs further research. PMID- 27561240 TI - Ultrasociality: When institutions make a difference. AB - We present arguments that the analogy between humans and social insects is coincidental, rather than based upon real similarities. In their claims, Gowdy & Krall largely omit the role of institutions in the formation of complex societies, warfare, and regulation. They also offer no strong explanation for the expansion of agriculture despite its early detrimental effects except the "mistake hypothesis" (cf. Diamond 1987). PMID- 27561241 TI - The 'Harris criterion' lives on. PMID- 27561244 TI - Comparison of plant and bacterial communities between a subtropical landfill topsoil 15years after restoration and a natural area. AB - Engineered sanitary landfills are becoming more and more common worldwide. Ecosystem restoration of capped sanitary landfills is essential to restore the disturbed environment. Comparing plant communities, as well as bacterial communities, in landfills and natural areas, offers an efficient way to assess the restoration status. However, such studies on the restored engineered landfills are limited. Here we present an ecological restoration case in an engineered landfill in a subtropical region. Part of the South East New Territories (SENT) landfill in Hong Kong was capped and restored, by using 16 plant species growing on top of the final cover soil, during 1997-1999. In 2014, plant survey and soil properties analyses were conducted in a restored site (AT) and a natural site (CT, an undisturbed area, serving as a control). The similarity between the biota communities (i.e., plant and soil bacteria) of the two sites was assessed. Plant and soil bacterial communities at AT were significantly different (R=1, P<0.01, ANOSIM) from those at CT. A lower plant diversity but a higher soil bacterial diversity were observed at AT. The soil bacterial community structure was potentially driven by soil pH, moisture content, cation exchange capacity (CEC), N, and P. The engineered landfill had not been restored to an ecosystem similar to the natural environment 15years after restoration. Establishing similar soil properties in the landfill topsoil would be important to achieve a bacterial community similar to the natural area. This study can also offer a quick and inexpensive method for landfill engineers to assess the bacterial restoration of man-made ecosystems using plant and soil properties rather than DNA analyzing techniques. PMID- 27561242 TI - Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology. AB - The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT-guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS-FNA), as well as recommendations for classification and criteria, ancillary testing and post-cytologic diagnosis management and follow up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next-generation sequencing are discussed. Diagn. Cytopathol. 2016;44:1000-1009. (c) 2016 Wiley Periodicals, Inc. PMID- 27561243 TI - The plastid metalloprotease FtsH6 and small heat shock protein HSP21 jointly regulate thermomemory in Arabidopsis. AB - Acquired tolerance to heat stress is an increased resistance to elevated temperature following a prior exposure to heat. The maintenance of acquired thermotolerance in the absence of intervening stress is called 'thermomemory' but the mechanistic basis for this memory is not well defined. Here we show that Arabidopsis HSP21, a plastidial small heat shock protein that rapidly accumulates after heat stress and remains abundant during the thermomemory phase, is a crucial component of thermomemory. Sustained memory requires that HSP21 levels remain high. Through pharmacological interrogation and transcriptome profiling, we show that the plastid-localized metalloprotease FtsH6 regulates HSP21 abundance. Lack of a functional FtsH6 protein promotes HSP21 accumulation during the later stages of thermomemory and increases thermomemory capacity. Our results thus reveal the presence of a plastidial FtsH6-HSP21 control module for thermomemory in plants. PMID- 27561245 TI - A European multicenter study on systematic ethics work in nursing homes. AB - BACKGROUND: There are many existing ethical challenges in nursing homes. Although different methods and approaches to discussing the ethical challenges have been established, systematic ethics work is not yet a standard in all nursing homes. The aim of the present study was to explore ethical challenges and approaches to implementing systematic ethics work in nursing homes. METHODS: Data from five institutions in Austria, Germany and Norway were collected, and a mixed-methods two-tiered study approach was chosen. Documentation of ethics discussions was combined with qualitative focus group interviews with staff members regarding the implementation of systematic ethics work in nursing homes. RESULTS: One hundred and five ethics meetings were documented. The main topics were advance care planning, ethical challenges associated with artificial nutrition, hospitalisation and end-of-life decision-making. Of the meetings, 33% focused mainly on everyday ethical challenges. In 76% of prospective case discussions, agreements about a solution were reached; however, in 29% of these no residents or relatives participated. The advantages of systematic ethics work described by the staff were enhanced openness and dialogue, overall, and a greater ethical awareness. Many voiced a need for structure and support from the administration. CONCLUSIONS: Systematic ethics work is greatly appreciated by the staff and helps to reach a consensus in the majority of case discussions. It should be implemented in all nursing homes. Attention to everyday ethical challenges is important. The participation of relatives and physicians could be improved. The participation of the residents' in ethics discussions should be encouraged to strengthen their autonomy and dignity. PMID- 27561246 TI - Turbulent jet flow generated downstream of a low temperature dielectric barrier atmospheric pressure plasma device. AB - Flowing low temperature atmospheric pressure plasma devices have been used in many technological applications ranging from energy efficient combustion through to wound healing and cancer therapy. The generation of the plasma causes a sudden onset of turbulence in the inhomogeneous axisymmetric jet flow downstream of the plasma plume. The mean turbulent velocity fields are shown to be self-similar and independent of the applied voltage used to generate the plasma. It is proposed that the production of turbulence is related to a combination of the small amplitude plasma induced body forces and gas heating causing perturbations in the unstable shear layers at the jet exit which grow as they move downstream, creating turbulence. PMID- 27561247 TI - Orthopaedic nursing challenges in poly-traumatised patient management: A critical analysis of an Orthopaedic and Trauma Unit. AB - INTRODUCTION AND BACKGROUND: Trauma is the most frequent cause of death in people under 40 years old. It is an important problem not only because of the high mortality but also because of the consequential disability that can lead to serious economic consequences. STUDY AIMS: This descriptive, comparative study investigates the definitive management of poly-traumatised patients in an Italian Orthopaedic Ward in order to highlight its strengths and weaknesses in comparison with the most recent literature. This has led to the development of a pre established algorithm for evaluation, preventive care and management of the poly trauma patient and a flow-chart for improved patient care. RESEARCH METHODS: A five-step observational and exploratory approach was employed in this study which critically analysed the nursing management of 60 multiple trauma patients admitted to our Orthopaedic Unit from April 2013 to October 2014. RESULTS: The findings highlight the need for adherence to plans of care, which can be approached by a shared management of poly-trauma patients that involves the medical team, the patient and his family/caregiver. DISCUSSION: The protocols and guidelines in use in our Orthopaedic and Trauma Unit are in line with European standards, although there is still margin for improvement. The study has led to the development of an algorithm that allows health professionals to have reference values for the care of polytrauma patients. CONCLUSIONS AND RECOMMENDATIONS: This study demonstrates the use of theoretical and practical tools for the evaluation and management of poly-traumatised patients during their hospital stay. We recommend the use of both proposed tools: the general algorithm and the flow-chart for the management of the poly-trauma patient, as they allow identification of barriers and facilitators related to the implementation of international guidelines, currently well-defined for Emergency Departments but not yet for Orthopaedic Units. PMID- 27561248 TI - Traction survival skills. PMID- 27561250 TI - Distribution of Plasmodium species on the island of Grande Comore on the basis of DNA extracted from rapid diagnostic tests. AB - In the Union of Comoros, interventions for combating malaria have contributed to a spectacular decrease in the prevalence of the disease. We studied the current distribution of Plasmodium species on the island of Grande Comore using nested PCR. The rapid diagnostic tests (RDTs) currently used in the Comoros are able to identify Plasmodium falciparum but no other Plasmodium species. In this study, we tested 211 RDTs (158 positive and 53 negative). Among the 158 positive RDTs, 22 were positive for HRP2, 3 were positive only for pLDH, and 133 were positive for HRP2 and pLDH. DNA was extracted from a proximal part of the nitrocellulose membrane of RDTs. A total of 159 samples were positive by nested PCR. Of those, 156 (98.11%) were positive for P. falciparum, 2 (1.25%) were positive for P. vivaxI, and 1 (0.62%) was positive for P. malariae. None of the samples were positive for P. ovale. Our results show that P. falciparum is still the most dominant species on the island of Grande Comore, but P. vivax and P. malariae are present at a low prevalence. PMID- 27561249 TI - Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis. AB - Bacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosomal proteins, which mobilize zinc from the ribosome, whereas the second includes the ZnuACB uptake system and the YciC metallochaperone. Finally, as zinc levels decrease further, the Zur2:Zn3 form loses Zn(II) leading to derepression of RpsNB(S14*) and FolE2, which allow continued ribosome assembly and folate synthesis, respectively. We infer that zinc mobilization from intracellular zinc stores takes priority over energy dependent import, and our results link the biochemistry of zinc sensing by Zur to the molecular logic of the zinc deprivation response. PMID- 27561251 TI - Anti-inflammatory effects of melatonin in multiple sclerosis. AB - Melatonin is a hormone with complex roles in the pathogenesis of autoimmune disorders. Over the years, it has become clear that melatonin may exacerbate some autoimmune conditions, whereas it alleviates others such as multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by a dysregulated immune response directed against the central nervous system. Indeed, the balance between pathogenic CD4(+) T cells secreting IFN-gamma (TH 1) or IL-17 (TH 17); and FoxP3(+) regulatory T cells and IL-10(+) type 1 regulatory T cells (Tr1 cells) is thought to play an important role in disease activity. Recent evidence suggests that melatonin ameliorates multiple sclerosis by controlling the balance between effector and regulatory cells, suggesting that melatonin-triggered signaling pathways are potential targets for therapeutic intervention. Here, we review the available data on the effects of melatonin on immune processes relevant for MS and discuss its therapeutic potential. PMID- 27561252 TI - Squeezing through the Now-or-Never bottleneck: Reconnecting language processing, acquisition, change, and structure. AB - If human language must be squeezed through a narrow cognitive bottleneck, what are the implications for language processing, acquisition, change, and structure? In our target article, we suggested that the implications are far-reaching and form the basis of an integrated account of many apparently unconnected aspects of language and language processing, as well as suggesting revision of many existing theoretical accounts. With some exceptions, commentators were generally supportive both of the existence of the bottleneck and its potential implications. Many commentators suggested additional theoretical and linguistic nuances and extensions, links with prior work, and relevant computational and neuroscientific considerations; some argued for related but distinct viewpoints; a few, though, felt traditional perspectives were being abandoned too readily. Our response attempts to build on the many suggestions raised by the commentators and to engage constructively with challenges to our approach. PMID- 27561253 TI - Homologous and heterologous expression of grapevine E-(beta)-caryophyllene synthase (VvGwECar2). AB - E-(beta)-caryophyllene is a sesquiterpene volatile emitted by plants and involved in many ecological interactions within and among trophic levels and it has a kairomonal activity for many insect species. In grapevine it is a key compound for host-plant recognition by the European grapevine moth, Lobesia botrana, together with other two sesquiterpenes. In grapevine E-(beta)-caryophyllene synthase is coded by the VvGwECar2 gene, although complete characterization of the corresponding protein has not yet been achieved. Here we performed the characterization of the enzyme after heterologous expression in E. coli, which resulted to produce in vitro also minor amounts of the isomer alpha-humulene and of germacrene D. The pH optimum was estimated to be 7.8, and the Km and Kcat values for farnesyl pyrophosphate were 31.4 MUM and 0.19 s-1 respectively. Then, we overexpressed the gene in the cytoplasm of two plant species, Arabidopsis thaliana and the native host Vitis vinifera. In Arabidopsis the enzyme changed the plant head space release, showing a higher selectivity for E-(beta) caryophyllene, but also the production of thujopsene instead of germacrene D. Overall plants increased the E-(beta)-caryophyllene emission in the headspace collection by 8-fold compared to Col-0 control plants. In grapevine VvGwECar2 overexpression resulted in higher E-(beta)-caryophyllene emissions, although there was no clear correlation between gene activity and sesquiterpene quantity, suggesting a key role by the plant regulation machinery. PMID- 27561254 TI - Nitric oxide inhibitory xanthones from the pericarps of Garcinia mangostana. AB - Mangosteen (Garcinia mangostana, Clusiaceae) is called "queen of fruit" in Southeast Asia. In the current study, three dimeric xanthones, garcinoxanthones A C, and four monomeric xanthones, garcinoxanthones D-G, together with 18 known xanthones, were isolated from the pericarps of G. mangostana, collected in Thailand. The structures of garcinoxanthones A-G were elucidated by analysis of their 1D and 2D NMR and other spectroscopic data, and their absolute configurations were determined by the CD spectra. All seven compounds were tested for nitric oxide (NO) inhibitory activity on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Garcinoxanthones B and C significantly inhibited NO production with IC50 values of 11.3 +/- 1.7 and 18.0 +/- 1.8 MUM, respectively, which were comparable with the positive control indomethacin (IC50 3.9 +/- 0.3 MUM). Moreover, garcinoxanthone B suppressed inducible NO synthase expression in a dose dependent manner. These results reveal the presence of rare dimeric xanthones in G. mangostana and their NO inhibitory effect on LPS-stimulated murine macrophage cells. PMID- 27561255 TI - Association between serum non-high-density lipoprotein cholesterol and cognitive impairment in patients with acute ischemic stroke. AB - BACKGROUND: Non-high density lipoprotein cholesterol (HDL-C) could be a good predictor of vascular disease outcomes. To evaluate the association between serum non-HDL-C and cognitive impairment in patients with acute ischemic stroke. METHODS: A total of 725 hospitalized patients with acute ischemic stroke were enrolled. They received conventional treatment. Cognitive function was assessed on the 3rd day after admission using mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Activity of Daily Living Scale (ADL), and Neuropsychiatric Inventory (NPI, and Hamilton depression rating scale 21-item (HAMD-21). Lipid profile and biochemical markers were measured, and non-HDL-C was calculated. RESULTS: Compared with patients with normal non-HDL-C, those with high non-HDL-C showed lower MMSE (23.1 +/- 4.9 vs. 26.0 +/- 4.6, P < 0.001) and MoCA (20.4 +/- 6.4 vs. 22.2 +/- 5.3 P = 0.01) scores, higher NPI (6.2 +/- 1.2 vs. 3.3 +/- 1.5, P < 0.001) and HADM-21 (6.0 +/- 2.2 vs. 4.5 +/- 1.9, P < 0.001) scores, and higher homocysteine (16.0 +/- 3.8 vs. 14.3 +/- 2.0 mmol/L, P = 0.044), fasting blood glucose (6.4 +/- 2.7 vs. 6.1 +/- 2.1 mmol/L, P = 0.041), and HbA1c (6.80 +/- 1.32 % vs. 6.52 +/- 1.17 %, P = 0.013) levels. MMSE (r = 0.526, P < 0.001), MoCA (r = -0.216, P < 0.001), and NPI (r = 0.403, P < 0.001) scores were correlated with non-HDL-C levels. High non-HDL-C levels were an independent risk factor for cognitive disorders after acute ischemic stroke (P = 0.034, odds ratio = 3.115, 95 % confidence interval: 1.088-8.917). CONCLUSIONS: High serum non-HDL-C levels, age, education, homocysteine levels, and HAMD score were independent risk factors of cognitive impairment in patients with acute ischemic stroke. The risk of cognitive disorders after acute ischemic stroke increased with increasing non-HDL-C levels. This parameter is easy to assess in the clinical setting. PMID- 27561257 TI - Nonomuraea purpurea sp. nov., an actinomycete isolated from mangrove sediment. AB - A polyphasic approach was used to verify the novel actinomycete, strain 1SM4-01T, isolated from mangrove sediment collected from Ranong Province, Thailand. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the organism was a member of the genus Nonomuraea and was most closely related to Nonomuraea syzygii GKU 164T (98.7 % sequence similarity), Nonomuraea rhizophila YIM 67092T (98.4 %), Nonomuraea solani NEAU-Z6T (98.4 %), Nonomuraea monospora PT708T (98.3 %) and Nonomuraea thailandensis KC-061T (98.2 %). The strain produced branching aerial mycelium which differentiated into straight chains of rough-surfaced spores borne at the end of a short sporophore. The whole-cell hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid, with madurose, mannose and ribose as the main sugars. MK-9(H4) was a major menaquinone of this strain. The acyl type of peptidoglycan was N-acetyl. The predominant cellular fatty acids were C17 : 1omega8c and iso-C16 : 0. Phospholipids consisted of diphosphatidylglycerol, hydroxy phosphatidylethanolamine, hydroxy-phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, aminophospholipids and unidentified lipids. The G+C content of the genomic DNA was 70.4 mol%. On the basis of phenotypic characteristics, DNA-DNA relatedness and phylogenetic distinctiveness, strain 1SM4-01T represents a novel species of the genus Nonomuraea, for which the name Nonomuraea purpurea sp. nov. is proposed. The type strain is 1SM4-01T (=BCC 60397T=NBRC 109647T). PMID- 27561256 TI - A dyadic approach to understanding the impact of breast cancer on relationships between partners during early survivorship. AB - BACKGROUND: The shared impact of breast cancer for women and their male partners is emerging as an important consideration during the experience of a breast cancer diagnosis, particularly during survivorship. This study aimed to explore the experiences of women and their partners during early survivorship and contributes a range of insights into the lives of those intimately affected by breast cancer. METHODS: In-depth interviews were completed with Australian women survivors of breast cancer (n = 8) and their partners (n = 8), between six months and five years following cessation of treatment. Questions included a focus on the women and their partners' daily experiences during early survivorship, including the management of ongoing symptoms, engagement in leisure and social interests, returning to work, communicating with each other, maintenance of the current relationship and other important roles and responsibilities. Thematic analysis was employed to determine key themes arising from the dyadic accounts of women and their partners' experiences during early breast cancer survivorship. RESULTS: Women and their partners experienced many changes to their previous roles, responsibilities and relationships during early breast cancer survivorship. Couples also reported a range of communication, intimacy and sexuality concerns which greatly impacted their interactions with each other, adding further demands on the relationship. Three significant themes were determined: (1) a disconnection within the relationship - this was expressed as the woman survivor of breast cancer needing to prioritise her own needs, sometimes at the expense of her partner and the relationship; (2) reformulating the relationship - this reflects the strategies used by couples to negotiate changes within the relationship; and (3) support is needed to negotiate the future of the relationship - couples emphasised the need for additional support and resources to assist them in maintaining their relationship during early survivorship. CONCLUSION: It can be concluded that the early survivorship period represents a crucial time for both women and their partners and there are currently limited options available to meet their shared needs and preferences for support. Findings indicate that a suitable model of care underpinned by a biopsychosocial framework, access to comprehensive assessment, timely support and the provision of targeted resources are urgently needed to assist women and their partners during this critical time. PMID- 27561258 TI - A longitudinal study on quality of life after injury in children. AB - BACKGROUND: In high income countries, injuries account for 40 % of all child deaths, representing the leading cause of child mortality and a major source of morbidity. The need for studies across age groups, and use of health related quality of life measures that assess functional limitations in multiple health domains, with sampling at specific post-injury time points has been identified. The objective of this study was to describe the impact of childhood injury and recovery on health related quality of life (HRQoL) for the 12 months after injury. METHODS: In this prospective cohort study parents of children 0-16 years old attending British Columbia Children's Hospital for an injury were surveyed over 12 months post-injury. Surveys assessed HRQoL at four points: baseline (pre injury), one month, four to six months and 12 months post injury. Generalized estimating equation models identified factors associated with changes in HRQoL over time. RESULTS: A total of 256 baseline surveys were completed. Response rates for follow-ups at one, four and twelve months were 74 % (186), 67 % (169) and 64 % (161), respectively. The mean age of participants was 7.9 years and 30 % were admitted to the hospital. At baseline, a retrospective measure of pre-injury health, the mean HRQoL score was 90.7. Mean HRQoL ratings at one, four and 12 months post injury were 77.8, 90.3 and 91.3, respectively. Both being older and being hospitalized were associated with a steeper slope to recovery. CONCLUSIONS: Although injuries are prevalent, the long term impacts of most childhood injuries are limited. Regardless of injury severity, most injured children recuperated quickly, and had regained total baseline status by four month post-injury. However, although hospitalization did not appear to impact long term psychosocial recovery, at four and 12 months post injury a greater proportion of hospitalized children continued to have depressed physical HRQoL scores. Both older and hospitalized children reported greater impact to HRQoL at one month post injury, and both had a steeper slope to recovery and were on par with their peers by four month. PMID- 27561259 TI - Recommendations for the transition of patients with ADHD from child to adult healthcare services: a consensus statement from the UK adult ADHD network. AB - The aim of this consensus statement was to discuss transition of patients with ADHD from child to adult healthcare services, and formulate recommendations to facilitate successful transition. An expert workshop was convened in June 2012 by the UK Adult ADHD Network (UKAAN), attended by a multidisciplinary team of mental health professionals, allied professionals and patients. It was concluded that transitions must be planned through joint meetings involving referring/receiving services, patients and their families. Negotiation may be required to balance parental desire for continued involvement in their child's care, and the child's growing autonomy. Clear transition protocols can maintain standards of care, detailing relevant timeframes, responsibilities of agencies and preparing contingencies. Transition should be viewed as a process not an event, and should normally occur by the age of 18, however flexibility is required to accommodate individual needs. Transition is often poorly experienced, and adherence to clear recommendations is necessary to ensure effective transition and prevent drop-out from services. PMID- 27561260 TI - Pyruvate kinase is necessary for Brucella abortus full virulence in BALB/c mouse. AB - Brucellosis, caused by a facultative intracellular pathogen Brucella, is one of the most prevalent zoonosis worldwide. Host infection relies on several uncanonical virulence factors. A recent research hotpot is the links between carbon metabolism and bacterial virulence. In this study, we found that a carbon metabolism-related pyruvate kinase (Pyk) encoded by pyk gene (locus tag BAB_RS24320) was associated with Brucella virulence. Determination of bacterial growth curves and resistance to environmental stress factors showed that Pyk plays an important role in B. abortus growth, especially under the conditions of nutrition deprivation, and resistance to oxidative stress. Additionally, cell infection assay showed that Pyk is necessary for B. abortus survival and evading fusion with lysosomes within RAW264.7 cells. Moreover, animal experiments exhibited that the Pyk deletion significantly reduced B. abortus virulence in a mouse infection model. Our results elucidated the role of the Pyk in B. abortus virulence and provided information for further investigation of Brucella virulence associated carbon metabolism. PMID- 27561261 TI - Erratum to: Life habits, hox genes, and affinities of a 311 million-year-old holometabolan larva. PMID- 27561262 TI - Insufficient Job Control among Gastroenterology Trainees: Time to Focus on the Science. PMID- 27561263 TI - Endoscopic Mucosal Resection versus Endoscopic Submucosal Dissection for Large Polyps: A Western Colonoscopist's View. AB - To discuss the rationale for the widespread application of endoscopic mucosal resection (EMR) rather than endoscopic submucosal dissection (ESD) in Western centers. In Western centers, EMR is the treatment of choice for most non pedunculated colorectal adenomas >2 cm in size. EMR is sufficiently effective and safe to be performed without post-procedure hospitalization. Advances in EMR have led to reduced recurrence rates, and recent studies have demonstrated excellent outcomes with endoscopic treatment of recurrent adenomas. While studies from Asia have demonstrated lower recurrence rates with ESD, concern about the higher perforation risk and lengthy procedure time of ESD are two of the barriers preventing widespread adoption of ESD in the West. EMR is likely to continue as the dominant method for the treatment of large colorectal adenomas in Western centers until the limitations of ESD are overcome. PMID- 27561264 TI - The Human Atrial Fibrosis Pathway in the Development of Atrial Fibrillation. PMID- 27561265 TI - Mathematical Modelling of Bacterial Quorum Sensing: A Review. AB - Bacterial quorum sensing (QS) refers to the process of cell-to-cell bacterial communication enabled through the production and sensing of the local concentration of small molecules called autoinducers to regulate the production of gene products (e.g. enzymes or virulence factors). Through autoinducers, bacteria interact with individuals of the same species, other bacterial species, and with their host. Among QS-regulated processes mediated through autoinducers are aggregation, biofilm formation, bioluminescence, and sporulation. Autoinducers are therefore "master" regulators of bacterial lifestyles. For over 10 years, mathematical modelling of QS has sought, in parallel to experimental discoveries, to elucidate the mechanisms regulating this process. In this review, we present the progress in mathematical modelling of QS, highlighting the various theoretical approaches that have been used and discussing some of the insights that have emerged. Modelling of QS has benefited almost from the onset of the involvement of experimentalists, with many of the papers which we review, published in non-mathematical journals. This review therefore attempts to give a broad overview of the topic to the mathematical biology community, as well as the current modelling efforts and future challenges. PMID- 27561266 TI - High prevalence of potential drug-drug interactions in patients with castration resistant prostate cancer treated with abiraterone acetate. AB - PURPOSE: Abiraterone acetate (AA), used to treat metastatic castration-resistant prostate cancer (mCRPC), inhibits androgen biosynthesis by blocking cytochrome P450 (CYP) 17A1. It also inhibits other cytochromes involved in the metabolism of various widely used medications. As such, there is presumably a high potential for drug-drug interactions (DDIs) that can diminish the efficacy of AA or concurrent medications, or increase the risk of DDI-related adverse events (AEs). However, the scale of AA-associated DDIs is currently unknown. METHODS: We conducted a retrospective review of pharmacy records and electronic patient charts to retrieve individual drug histories and on-treatment AEs of mCRPC patients beginning AA therapy in a tertiary care setting. Potential DDIs were analyzed using two commercial databases, Lexicomp and Micromedex. RESULTS: Eighty four informative patients were identified. Sixty-five patients (77 %) and 44 patients (52 %) were flagged for one or more potential DDIs by the Lexicomp and Micromedex databases, respectively. One hundred eighty-four potential DDIs were identified overall, with a median of 1 DDI per patient in both databases. Possibly due to rigorous DDI screening before AA treatment initiation, we did not identify a definite instance of DDI-related AEs. CONCLUSIONS: The use of commercial DDI databases suggests a substantial risk of potentially consequential DDIs in mCRPC patients undergoing AA therapy. However, prospective investigations with larger patient populations are required to better establish the clinical relevance of these DDIs. PMID- 27561267 TI - Evaluation of the pharmacokinetics of glibenclamide tablet given, off label, orally to children suffering from neonatal syndromic hyperglycemia. AB - PURPOSE: Glibenclamide (Gb) is used in type II diabetes mellitus but also in the last 10 years, off label, in patients with neonatal syndromic hyperglycemia carrying a mutation of Kir6.2 or SUR1. No studies have reported Gb pharmacokinetics in children. In this study, oral Gb pharmacokinetics was investigated in children in order to describe the concentration time courses, the influence of covariates, and the relationships between drug concentrations and efficacy. METHODS: Gb concentrations were measured in 18 children after the switch from subcutaneous insulin to oral tablets of Gb (crushed tablets for 33 % of patients). A total of 229 plasma Gb concentrations and 187 blood glucose measurements were available. A population model was developed with NONMEM. RESULTS: Body weight was the most significant parameter on clearance and explained a substantial part of the variability. A variant genotype of CYP2C9 (i.e., *1/*2 and *1/*3) explained also a part of the remaining variability on Gb clearance. Patients carrying these allelic variants had a clearance decreased by 45 %. A link between daily area under the curve (AUC0-24 h) and metabolic control diabetes was found. CONCLUSIONS: This study evaluates for the first time the pharmacokinetics of oral Gb in children and constitutes a first step towards dose individualization of this drug in a particularly vulnerable population. PMID- 27561268 TI - Response: Co-administration of cyclosporine A and imatinib among patients with Philadelphia chromosome-positive leukemias in the post-transplant setting. PMID- 27561269 TI - Working relationships between obstetric care staff and their managers: a critical incident analysis. AB - BACKGROUND: Malawi continues to experience critical shortages of key health technical cadres that can adequately respond to Malawi's disease burden. Difficult working conditions contribute to low morale and frustration among health care workers. We aimed to understand how obstetric care staff perceive their working relationships with managers. METHODS: A qualitative exploratory study was conducted in health facilities in Malawi between October and December 2008. Critical Incident Analysis interviews were done in government district hospitals, faith-based health facilities, and a sample of health centres' providing emergency obstetric care. A total of 84 service providers were interviewed. Data were analyzed using NVivo 8 software. RESULTS: Poor leadership styles affected working relationships between obstetric care staff and their managers. Main concerns were managers' lack of support for staff welfare and staff performance, lack of mentorship for new staff and junior colleagues, as well as inadequate supportive supervision. All this led to frustrations, diminished motivation, lack of interest in their job and withdrawal from work, including staff seriously considering leaving their post. CONCLUSIONS: Positive working relationships between obstetric care staff and their managers are essential for promoting staff motivation and positive work performance. However, this study revealed that staff were demotivated and undermined by transactional leadership styles and behavior, evidenced by management by exception and lack of feedback or recognition. A shift to transformational leadership in nurse-manager relationships is essential to establish good working relationships with staff. Improved providers' job satisfaction and staff retentionare crucial to the provision of high quality care and will also ensure efficiency in health care delivery in Malawi. PMID- 27561270 TI - Health-related quality of life in mucopolysaccharidosis: looking beyond biomedical issues. AB - The mucopolysaccharidoses (MPS) comprise a heterogeneous family of rare, genetic lysosomal storage disorders that result in severe morbidity and reduced life expectancy. Emerging treatments for several of these disorders have triggered the search for clinically relevant biomarkers and clinical markers associated with treatment efficacy in populations and individuals. However, biomedical measures do not tell the whole story when characterizing a complex chronic disorder such as MPS. Health-related quality of life (HRQoL) tools that utilize patient reported outcomes to address patient parameters such as symptoms (pain, fatigue, psychological health), functioning (activity and limitations), or quality of life, have been used to supplement traditional biomedical endpoints. Many of these HRQoL tools have demonstrated that quality of life is negatively impacted in patients with MPS. There is both the opportunity and need to formally standardize and validate HRQoL tools for the different MPS disorders. PMID- 27561271 TI - Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene. AB - Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 (PTCH1) gene. To date, we have detected 73 mutations in PTCH1 and ten of them (14 %) were suspected splicing mutations. Eight out of the ten mutations were localized near the splice donor site. Five mutations were localized within the invariant GT-AG splice site, whereas the other five mutations occurred outside the invariant GT AG site including the last exonic nucleotide. When the transcripts were examined, all mutations resulted in aberrant splicing, including exon skipping or the activation of cryptic splice sites. This is the first extensive report of NBCCS focusing on splice site mutations, and it highlights the importance of analyzing transcripts especially for mutations lying outside the GT-AG splicing consensus site. In addition, the splice site score calculated by Splice-Site Analyzer Tool provided by Tel Aviv University helped predict aberrant splice patterns in most of the cases. PMID- 27561273 TI - Reply to the Letter "Interventional Radiology-The Future: Evolution or Extinction?" PMID- 27561272 TI - Discovery and Clinical Evaluation of MK-8150, A Novel Nitric Oxide Donor With a Unique Mechanism of Nitric Oxide Release. AB - BACKGROUND: Nitric oxide donors are widely used to treat cardiovascular disease, but their major limitation is the development of tolerance, a multifactorial process to which the in vivo release of nitric oxide is thought to contribute. Here we describe the preclinical and clinical results of a translational drug development effort to create a next-generation nitric oxide donor with improved pharmacokinetic properties and a unique mechanism of nitric oxide release through CYP3A4 metabolism that was designed to circumvent the development of tolerance. METHODS AND RESULTS: Single- and multiple-dose studies in telemetered dogs showed that MK-8150 induced robust blood-pressure lowering that was sustained over 14 days. The molecule was safe and well tolerated in humans, and single doses reduced systolic blood pressure by 5 to 20 mm Hg in hypertensive patients. Multiple-dose studies in hypertensive patients showed that the blood-pressure lowering effect diminished after 10 days, and 28-day studies showed that the hemodynamic effects were completely lost by day 28, even when the dose of MK-8150 was increased during the dosing period. CONCLUSIONS: The novel nitric oxide donor MK-8150 induced significant blood-pressure lowering in dogs and humans for up to 14 days. However, despite a unique mechanism of nitric oxide release mediated by CYP3A4 metabolism, tolerance developed over 28 days, suggesting that tolerance to nitric oxide donors is multifactorial and cannot be overcome solely through altered in vivo release of nitric oxide. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01590810 and NCT01656408. PMID- 27561274 TI - Endovascular Retrieval of Entrapped Elephant Trunk Graft During Complex Hybrid Aortic Arch Repair. AB - Entrapment of the elephant trunk graft within the false lumen is a rare complication of surgical repair of an aortic dissection. This is normally retrieved by emergent open surgery. We describe a technique of endovascular retrieval of the dislodged graft, during hybrid aortic arch repair. The elephant trunk was cannulated through and through from a femoral access and the free end of the wire was snared and retrieved from a brachial access. The wire was externalised from both accesses and was used to reposition the graft into the true lumen using a body flossing technique. PMID- 27561275 TI - Interventional Radiology-The Future: Evolution or Extinction? PMID- 27561276 TI - Infant Mental Health Training for Child and Adolescent Psychiatry: A Comprehensive Model. PMID- 27561277 TI - The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands. AB - There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients. PMID- 27561278 TI - Erythropoietin stimulates the coronary collateral development in patients with coronary chronic total occlusion. AB - OBJECTIVE: Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion. METHODS: A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3). RESULTS: There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = -0.210, p = 0.006). CONCLUSIONS: Serum EPO is a useful biomarker for coronary collateral development in patients with CTO. PMID- 27561279 TI - Chronic fatigue syndrome in women assessed with combined cardiac magnetic resonance imaging. AB - OBJECTIVE: In chronic fatigue syndrome (CFS), only a few imaging and histopathological studies have previously assessed either cardiac dimensions/function or myocardial tissue, suggesting smaller left ventricular (LV) dimensions, LV wall motion abnormalities and occasionally viral persistence that may lead to cardiomyopathy. The present study with cardiac magnetic resonance (CMR) imaging is the first to use a contrast-enhanced approach to assess cardiac involvement, including tissue characterisation of the LV wall. METHODS: CMR measurements of 12 female CFS patients were compared with data of 36 age-matched, healthy female controls. With cine imaging, LV volumes, ejection fraction (EF), mass, and wall motion abnormalities were assessed. T2-weighted images were analysed for increased signal intensity, reflecting oedema (i. e. inflammation). In addition, the presence of contrast enhancement, reflecting fibrosis (i. e. myocardial damage), was analysed. RESULTS: When comparing CFS patients and healthy controls, LVEF (57.9 +/- 4.3 % vs. 63.7 +/- 3.7 %; p < 0.01), end-diastolic diameter (44 +/- 3.7 mm vs. 49 +/- 3.7 mm; p < 0.01), as well as body surface area corrected LV end-diastolic volume (77.5 +/- 6.2 ml/m2 vs. 86.0 +/- 9.3 ml/m2; p < 0.01), stroke volume (44.9 +/- 4.5 ml/m2 vs. 54.9 +/- 6.3 ml/m2; p < 0.001), and mass (39.8 +/- 6.5 g/m2 vs. 49.6 +/- 7.1 g/m2; p = 0.02) were significantly lower in patients. Wall motion abnormalities were observed in four patients and contrast enhancement (fibrosis) in three; none of the controls showed wall motion abnormalities or contrast enhancement. None of the patients or controls showed increased signal intensity on the T2-weighted images. CONCLUSION: In patients with CFS, CMR demonstrated lower LV dimensions and a mildly reduced LV function. The presence of myocardial fibrosis in some CFS patients suggests that CMR assessment of cardiac involvement is warranted as part of the scientific exploration, which may imply serial non-invasive examinations. PMID- 27561280 TI - Effect of statins on coronary blood flow after percutaneous coronary intervention in patients with stable coronary artery disease. AB - AIMS: Statins have favourable effects on the vascular system. However, few data are available regarding the effect of these drugs on patients undergoing percutaneous coronary intervention (PCI). We sought to determine the impact of prior statin use on coronary blood flow after PCI in patients with stable coronary artery disease (CAD) by using the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). METHODS: A total of 80 consecutive eligible patients (mean age: 60 +/- 7 years, 65 % male) with the diagnosis of stable CAD who were hospitalised for elective PCI were retrospectively enrolled in our study. The study population was divided into two groups according to statin use at least 6 months before PCI. Group 1 comprised of 51 patients (67 % male; mean age: 58 +/- 4 years) taking statins and group 2 comprised of 29 patients (62 % male; mean age: 60 +/- 3 years) not taking statins. PCI was applied to de novo type A lesions. CTFC was calculated for the treated vessels at baseline and after PCI. RESULTS: The two groups had similar characteristics in terms of age, sex, concomitant medications, lesion characteristics, pre-procedural CTFC, lipid parameters, and risk factors for CAD. Post-PCI CTFC (16 +/- 3 vs. 22 +/- 5, p = 0.01) and hs-CRP (2.1 +/- 0.7 mg/l vs. 6.1 +/- 2 mg/l, p = 0.01) in patients receiving statins before PCI were significantly lower than in patients without statin therapy. Multiple logistic regression analysis showed that statin pre treatment (OR 2.5, 95 % CI 1.2 to 3.8, p < 0.001) and hs-CRP level (OR 1.8, 95 % CI 1.2 to 2.4, p = 0.001) were independent predictors of post-PCI CTFC. CONCLUSIONS: In patients with stable CAD undergoing PCI, receipt of long-term statin therapy was associated with improvement in epicardial perfusion after PCI. PMID- 27561281 TI - Relationship between atrial septal defects and asthma-like dyspnoea: the impact of transcatheter closure. AB - BACKGROUND: Patients with atrial septal defects (ASD) are often misdiagnosed as asthma patients and accordingly receive erroneous bronchodilator treatment. In order to characterise their symptoms of dyspnoea to explain this clinical observation, we investigated the prevalence of asthma-like symptoms in patients with secundum ASD who then underwent successful percutaneous closure. METHODS: A total of 80 ASD patients (74 % female, mean age 46.7 +/- 16.8 years, median follow-up 3.0 [2.0-5.0] years) retrospectively completed dyspnoea questionnaires determining the presence and extent of cough, wheezing, chest tightness, effort dyspnoea and bronchodilator use on a 7-point scale (0 = none, 6 = maximum) before and after ASD closure. The Mini Asthma Quality of Life (Mini-AQLQ) and Asthma Control Questionnaire with bronchodilator use (ACQ6) were administered. RESULTS: A total of 48 (60 %) patients reported cough, 27 (34 %) wheezing, 26 (33 %) chest tightness and 62 (78 %) effort dyspnoea. Symptom resolution or reduction was found in 64 (80 %) patients after ASD closure. Asthma symptom scores decreased significantly on the Mini-AQLQ and ACQ6 (both p < 0.001). The number of patients using bronchodilators decreased from 16 (20 %) to 8 (10 %) patients after ASD closure (p = 0.039) with less frequent use of bronchodilators (p = 0.015). CONCLUSIONS: A high prevalence of asthma-like symptoms and bronchodilator use is present in ASD patients, which exceeds the low prevalence of bronchial asthma in this study population. Future prospective research is required to confirm this phenomenon. The presence of an ASD should be considered in the differential diagnosis of patients with asthma-like symptoms, after which significant symptom relief can be achieved by ASD closure. PMID- 27561282 TI - A longer life at the top of Mount Olympus? PMID- 27561283 TI - Effects of radial versus femoral artery access in patients with acute myocardial infarction: A large centre prospective registry. AB - AIM: This study sought to assess whether radial artery access improves clinical outcomes in patients presenting with acute myocardial infarction compared with femoral artery access. METHODS: This is a single-centre, prospective observational registry of all STEMI and NSTEMI patients who underwent coronary angiography and/or primary PCI in the period January 2010 to December 2013. Primary endpoint was 30-day all-cause mortality. Choice of access was left to the discretion of the cardiologist. Differences in the risk of death at 30 days between patients undergoing transradial intervention versus transfemoral intervention was assessed on an intention-to-treat comparison. RESULTS: Retrospective analysis of prospectively collected data was performed in 3580 patients with an acute coronary syndrome who underwent coronary angiography, of which 1310 had radial artery access. PCI was performed in 77 % of the patients. Before propensity score matching, patients who underwent transradial intervention and those intended to undergo transfemoral approach differed significantly in intra-aortic balloon pump use (1.7 % vs. 6.7 %, p < 0.001), and Killip class (Killip 1: 10.8 % vs. 17.3 %, p < 0.001). 30-day mortality rates were 1.7 % in the transradial group and 4.6 % in the transfemoral group (p < 0.001). After matching on the propensity score, the hazard ratio for 30-day mortality in the transradial group was 0.56 (95 % CI: 0.29-1.07, p = 0.08). CONCLUSION: This registry-based study showed that radial access is associated with improved outcome in patients with an acute coronary syndrome. However, this difference was no longer significant after multivariate and propensity score adjustment for differences in baseline characteristics. PMID- 27561284 TI - Incessant ventricular tachycardia. PMID- 27561285 TI - Incessant ventricular tachycardia. PMID- 27561286 TI - Utilisation of cardiac pacemakers over a 20-year period: Results from a nationwide pacemaker registry. AB - The implantation of cardiac pacemakers has become a well-established therapy for conduction disorders and sinus node dysfunction. In many countries pacemaker registries have been initiated in order to collect information on patient characteristics, trends in numbers and the types of pacemakers used, to identify problematic devices, and for safety monitoring. For this utilisation study the Central Pacemaker Patients Registration (CPPR) from the Netherlands Pacemaker Registry Foundation (CPPR-SPRN) containing data collected for more than 20 years was used. During this period nearly 97,000 first pacemakers were implanted. Analyses show an increase in the rate of implanted devices. The change in pacemaker type from VVI to DDD, followed by biventricular stimulation, is reflected by the number of simultaneously implanted leads, which is partly a consequence of cardiac resynchronisation therapy. Our data demonstrate that indications for implantation and type of pacemaker are comparable with other European countries. PMID- 27561287 TI - Transcriptome analysis reveals that constant heat stress modifies the metabolism and structure of the porcine longissimus dorsi skeletal muscle. AB - Exposure to high ambient temperatures is detrimental to pig rearing and porcine meat quality. Deep molecular sequencing allows for genomic characterization of porcine skeletal muscles and helps understand how the genomic landscape may impact meat quality. To this end, we performed mRNA-seq to molecularly dissect the impact of heat stress on porcine skeletal muscles, longissimus dorsi. Sixteen castrated, male DLY pigs [which are crossbreeds between Duroc (D) boars and Landrace (L) * Yorkshire (Y) sows, 79.0 +/- 1.5 kg BW] were evenly split into two groups that were subjected to either control (CON) (22 degrees C; 55 % humidity) or constant heat stress (H30; 30 degrees C; 55 % humidity) conditions for 21 days. Seventy-eight genes were found to be differentially expressed, of which 37 were up-regulated and 41 were down-regulated owing to constant heat stress. We predicted 5247 unknown genes and 6108 novel transcribed units attributed to alternative splicing (AS) events in the skeletal muscle. Furthermore, 30,761 and 31,360 AS events were observed in the CON and H30 RNA-seq libraries, respectively. The differentially expressed genes in the porcine skeletal muscles were involved in glycolysis, lactate metabolism, lipid metabolism, cellular defense, and stress responses. Additionally, the expression levels of these genes were associated with variations in meat quality between the CON and H30 groups, indicating that heat stress modulated genes crucial to skeletal muscle development and metabolism. Our transcriptomic analysis provides valuable information for understanding the molecular mechanisms governing porcine skeletal muscle development. Such insights may lead to innovative strategies to improve meat quality of pigs under heat stress. PMID- 27561288 TI - Corynebacterium diphtheriae HmuT: dissecting the roles of conserved residues in heme pocket stabilization. AB - The heme-binding protein HmuT is part of the Corynebacterium diphtheriae heme uptake pathway and is responsible for the delivery of heme to the HmuUV ABC transporter. HmuT binds heme with a conserved His/Tyr heme axial ligation motif. Sequence alignment revealed additional conserved residues of potential importance for heme binding: R237, Y272 and M292. In this study, site-directed mutations at these three positions provided insight into the nature of axial heme binding to the protein and its effect on the thermal stability of the heme-loaded protein fold. UV-visible absorbance, resonance Raman (rR) and thermal unfolding experiments, along with collision-induced dissociation electrospray ionization mass spectrometry, were used to probe the contributions of each mutated residue to the stability of pi HmuT. Thermal unfolding and rR experiments revealed that R237 and M292 are important residues for heme binding. Arginine 237 is a hydrogen bond donor to the phenol side chain of Y235, which serves as an axial heme ligand. Methionine 292 serves a supporting structural role, favoring the R237 hydrogen-bond donation, which elicits a, heretofore, unobserved modulating influence on pi donation by the axial tyrosine ligand in the heme carbonyl complex, HmuT-CO. PMID- 27561289 TI - Fibroblast Growth Factor 23 and Risk of CKD Progression in Children. AB - BACKGROUND AND OBJECTIVES: Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD in children. High FGF23 levels associate with progression of CKD in adults. Whether FGF23 predicts CKD progression in children is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tested the hypothesis that high plasma FGF23 is an independent risk factor for CKD progression in 419 children, aged 1-16 years, enrolled in the Chronic Kidney Disease in Children (CKiD) cohort study. We measured plasma FGF23 concentrations at baseline and determined GFR annually using plasma disappearance of iohexol or the CKiD study estimating equation. We analyzed the association of baseline FGF23 with risk of progression to the composite end point, defined as start of dialysis or kidney transplantation or 50% decline from baseline GFR, adjusted for demographics, baseline GFR, proteinuria, other CKD-specific factors, and other mineral metabolites. RESULTS: At enrollment, median age was 11 years [interquartile range (IQR), 8-15], GFR was 44 ml/min per 1.73 m2 (IQR, 33-57), and FGF23 was 132 RU/ml (IQR, 88-200). During a median follow-up of 5.5 years (IQR, 3.5-6.6), 32.5% of children reached the progression end point. Higher FGF23 concentrations were independently associated with higher risk of the composite outcome (fully adjusted hazard ratio, 2.52 in the highest versus lowest FGF23 tertile; 95% confidence interval, 1.44 to 4.39, P=0.002; fully adjusted hazard ratio, 1.33 per doubling of FGF23; 95% confidence interval, 1.13 to 1.56, P=0.001). The time to progression was 40% shorter for participants in the highest compared with the lowest FGF23 tertile. In contrast, serum phosphorus, vitamin D metabolites, and parathyroid hormone did not consistently associate with progression in adjusted analyses. CONCLUSIONS: High plasma FGF23 is an independent risk factor for CKD progression in children. PMID- 27561290 TI - Neuroprotective Effect of Matrine in Mouse Model of Vincristine-Induced Neuropathic Pain. AB - Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 MUg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21). Von Frey hair, hot plate, cold-plate and paw pressure tests were conducted to assess the degree of mechanical allodynia, thermal hyperalgesia, cold allodynia and mechanical hyperalgesia in the hind paw respectively. The electrophysiological and histopathological changes were also analyzed. Furthermore, tissue malondialdehyde (MDA), total antioxidant capacity (T AOC),superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total calcium (TCA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10) were measured to investigate possible involvement of MT in inflammation and oxidative stress. Administration of MT attenuated the VCR-induced behavioral alterations as well as electrophysiological and histopathological changes in a dose dependent manner. Further, MT also attenuated the VCR-induced oxidative stress (MDA, T-AOC, GSH-Px, SOD and TCA) and inflammation (MPO, TNF-alpha, IL-6 and IL-10). Taken together, MT ameliorated VCR-induced painful neuropathy, which might be attributed to neuroprotective effects by subsequent reduction in oxidative stress and anti inflammatory actions. PMID- 27561291 TI - Effects of Etomidate on GABAergic and Glutamatergic Transmission in Rat Thalamocortical Slices. AB - Although accumulative evidence indicates that the thalamocortical system is an important target for general anesthetics, the underlying mechanisms of anesthetic action on thalamocortical neurotransmission are not fully understood. The aim of the study is to explore the action of etomidate on glutamatergic and GABAergic transmission in rat thalamocortical slices by using whole cell patch-clamp recording. We found that etomidate mainly prolonged the decay time of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs), without changing the frequency. Furthermore, etomidate not only prolonged the decay time of miniature inhibitory postsynaptic currents (mIPSCs) but also increased the amplitude. On the other hand, etomidate significantly decreased the frequency of spontaneous glutamatergic excitatory postsynaptic currents (sEPSCs), without altering the amplitude or decay time in the absence of bicuculline. When GABAA receptors were blocked using bicuculline, the effects of etomidate on sEPSCs were mostly eliminated. These results suggest that etomidate enhances GABAergic transmission mainly through postsynaptic mechanism in thalamocortical neuronal network. Etomidate attenuates glutamatergic transmission predominantly through presynaptic action and requires presynaptic GABAA receptors involvement. PMID- 27561293 TI - Selenium Source Impacts Protection of Porcine Jejunal Epithelial Cells from Cadmium-Induced DNA Damage, with Maximum Protection Exhibited with Yeast-Derived Selenium Compounds. AB - Selenium (Se) is found in inorganic and organic forms, both of which are commonly used in animal feed supplements. The aim of this study was to determine the impact of the chemical form of Se on its associated ameliorative effects on cadmium (Cd)-induced DNA damage in a porcine model. At a cellular level, Cd mediates free oxygen radical production leading in particular to DNA damage, with consequential mutagenesis and inhibition of DNA replication. In this study, porcine jejunal epithelial cells (IPEC-J2) were pre-incubated for 48 h with one of Se-yeast (Sel-Plex), selenomethionine (Se-M), sodium selenite (Se-Ni) or sodium selenate (Se-Na). The effects of this supplementation on cell viability and DNA damage following cadmium chloride (CdCl2) exposure were subsequently evaluated. IPEC-J2 cells were cultivated throughout in medium supplemented with porcine serum to generate a superior model that recapitulated the porcine gut epithelium. The results illustrated that Se antioxidant effects were both composition- and dose-dependent as evident from cell viability (Alamar Blue and 5 carboxyfluorescein diacetate acetoxymethyl ester) and DNA damage assays (Comet and TUNEL). Both the Se-yeast and Se-M organic species, when used at the European Food Safety Authority guideline levels, had a protective effect against Cd induced DNA damage in the IPEC-J2 model system whereas for inorganic Se-Ni and Se Na sources no protective effects were observed and in fact these were shown to enhance the negative effects of Cd-induced DNA damage. It can be concluded that nutritional supplementation with organoselenium may protect porcine gut integrity from damage induced by Cd. PMID- 27561292 TI - Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats. AB - Arsenic trioxide (As2O3) is both the most prevalent, naturally occurring inorganic arsenical threatening human health and an efficient therapeutic for acute promyelocytic leukemia. Regretfully, As2O3-treated cancer patients often suffer from hepatotoxicity. While effective antioxidant and anticarcinogenic actions of allicin have previously been demonstrated, studies indicating how allicin affects As2O3-induced hepatotoxicity and arsenic accumulation are lacking. Our study, for the first time, elaborates potential details of the hepatoprotective mechanisms of allicin against As2O3-induced liver injury. Wistar rats were administrated allicin (30 mg/kg) 1 h before As2O3 (3 mg/kg) by daily gavage for 2 weeks. Our results indicate that allicin ameliorated As2O3-induced liver dysfunction, oxidative stress, and arsenic accumulation in the liver. Meanwhile, allicin decreased NF-kappaB level and upregulated expression of proteins reduced by As2O3 including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1, and Kruppel-like factor 9 (KLF9). In addition, allicin promoted B cell lymphoma-extra large expression and suppressed B cell lymphoma-2 associated X protein levels regulated by As2O3. However, neither allicin nor As2O3 affected cytochrome P450 2E1 mRNA expression. In conclusion, allicin attenuated As2O3-induced hepatotoxicity by activating the Nrf2 signaling pathway involving KLF9 to inhibit oxidative stress and apoptosis. Our findings elucidate a detailed mechanism by which allicin provides protection against As2O3-induced liver injury and support its potential role as an adjunctive therapy for patients suffering from chronic arsenic exposure. PMID- 27561294 TI - Ameliorative Effects of Dietary Selenium Against Cadmium Toxicity Is Related to Changes in Trace Elements in Chicken Kidneys. AB - The ameliorative effects of selenium (Se) against cadmium (Cd)-induced toxicity have been reported extensively. However, few studies have assessed the effects of multiple ions simultaneously on the variations of elements. In this study, the changes in Se, Cd, and 26 other element concentrations were investigated in chicken kidneys. One hundred and twenty-eight 31-week-old laying hens were fed a diet supplemented with either Se, Cd, or both Se and Cd for 90 days. The ion content was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). We found that the Se, Cd, and combined Se and Cd treatments significantly affected the trace elements in the chicken kidneys. The Cd supplement caused ion profile disorders, including reduced concentrations of V, Cr, Mn, Mo, As, Ba, Hg, Ti, and Pb and increased Si, Cu, Li, Cd, and Sb. The Se supplement reduced the contents of Co, Mo, and Pb and increased the contents of Cr, Fe, and Se. Moreover, Se also increased the concentrations of Cr, Mn, Zn, and Se and decreased those of Li and Pb, which in contrast were induced by Cd. Complex interactions between elements were analyzed, and both positive and negative correlations among these elements are presented. The present study indicated that Se can help against the negative effects of Cd and may be related to the homeostasis of the trace elements in chicken kidneys. PMID- 27561295 TI - Potential implications on female fertility and reproductive lifespan in BRCA germline mutation women. AB - PURPOSE: Women who carry a mutation in the BRCA1 or BRCA2 genes not only have an increased lifetime risk of developing breast and ovarian cancer, but also a complicated reproductive future. Based on the hypothesis that BRCA germline mutations (BRCAm) are associated with accelerated follicular loss and early menopause, the aim of this paper is to discuss and review the most outstanding recently published articles about BRCA gene and fertility. METHOD: A literature research in PubMed was conducted, using the keywords "anti-Mullerian hormone", "BRCA1/2 gene", "female fertility", "ovarian reserve" and "premature ovarian failure", selecting outstanding articles published since 2010. RESULTS: BRCA genes, mainly BRCA1, play a role in the maintenance of double-stranded DNA breaks and telomere length, a factor associated with reproductive lifespan and early depletion of ovarian reserve. BRCAm women have a decreased ovarian reserve and worse response in fertility preservation. In the case of being given chemotherapy or tamoxifen, that would increase the apoptosis of follicular reserve. Low Anti Mullerian hormone serum concentrations have not been shown to affect natural fecundability and fertility in BRCAm women below 30 s, but it does in women above that threshold. Surgical risk reduction salpingo-oophorectomy implies another important limitation in reproductive possibilities. Removal of the fallopian tubes with delayed oophorectomy could be a reasonable strategy in high-risk premenopausal women in the context of a clinical trial. CONCLUSIONS: BRCAm women should not delay pregnancy, especially if they are BRCA1, older than 35 years or with previous gonadotoxic treatments. Future prospective studies on infertility outcomes in this population are needed. PMID- 27561296 TI - Forgiveness Working: Forgiveness, Health, and Productivity in the Workplace. AB - PURPOSE: Associations between forgiveness and health promotion in the workplace were examined as mediating effects of workplace interpersonal stress. DESIGN: Cross-sectional. SETTING: Multiple Washington, DC, office-based and Midwestern manufacturing workplaces. PARTICIPANTS: Study 1: 108 employees (40 males and 68 females); mean age was 32.4 years. Study 2: 154 employees (14 males and 140 females); mean age was 43.9 years. MEASURES: Questionnaires measured forgiveness, unproductivity, absenteeism, stress, and health problems. ANALYSIS: Bivariate and multiple correlation/regression and structural equation models were used. Indirect effects were estimated with bootstrapping methods. RESULTS: In study 1, forgiveness of a specific workplace offense was inversely associated with unproductivity ( r = -.35, P < .001) and mental ( r = -.32, P = .001) and physical ( r = -.19, P = .044) health problems. In study 2, trait forgiveness was inversely associated with unproductivity (beta = -.20, P = .016) and mental (beta = -.31, P < .001) and physical health problems (beta = -.28, P = .001), and workplace interpersonal stress partially mediated these associations (indirect effects = -.03, -.04, -.05, respectively). CONCLUSION: The association of forgiveness and occupational outcomes is robust. Forgiveness may be associated with outcomes by (at least partially) reducing stress related to workplace offenses. Forgiveness may be an effective means of coping following being emotionally hurt on the job that may promote good health, well-being, and productivity. PMID- 27561297 TI - Examination of the Correlation Between Internet Addiction and Social Phobia in Adolescents. AB - This was a descriptive and cross-sectional study conducted with adolescents to examine the correlation between Internet addiction and social phobia. The population of the study consisted of 24,260 students aged between 11 and 15 years. Sampling method was used from population with known number, and 1,450 students were calculated as sample of the study. In this study, 13.7% of the adolescents had an Internet addiction, and 4.2% spent more than 5 hr on the computer every day. There was a positive correlation between Internet addiction and social phobia. The form of time spent on Internet was examined in terms of addiction and social phobia; although Internet addiction was related to games, dating sites, and web surfing, social phobia was related to homework, games, and web surfing. It was hypothesized that adolescents with social phobia were Internet addicts, and the participants used the Internet to spend time rather than socialize. PMID- 27561299 TI - Microstructural study of the lunate in stage III Kienbock's disease with micro computed tomography imaging. AB - Seventeen fresh lunates with stage III Kienbock's disease were scanned with micro computed tomography. Four regions of interest were selected to measure trabecular parameters, which were compared with those from normal lunates. Within the three regions in the distal surface, there was more compact trabecular bone in the middle region when compared with the palmar and dorsal regions. In the central part, the trabeculae of the Kienbock's lunates were much thicker than those in normal lunates. The diameters of the palmar nutrient foramina of the Kienbock's lunates were significantly smaller than those in normal lunates. In affected lunates, the bony disruptions were mostly located in the palmar or dorsal areas, which were shown from trabecular bone structure analysis to be structurally weaker. This leads to separation of the distal part of the fractured bone, disruption of the blood supply, poor bone remodelling and proneness to secondary fracture and eventual collapse. PMID- 27561300 TI - The magnetic resonance imaging appearances in Kienbock's disease. PMID- 27561298 TI - Accumulation of long-chain bases in yeast promotes their conversion to a long chain base vinyl ether. AB - Long-chain bases (LCBs) are the precursors to ceramide and sphingolipids in eukaryotic cells. They are formed by the action of serine palmitoyl-CoA transferase (SPT), a complex of integral membrane proteins located in the endoplasmic reticulum. SPT activity is negatively regulated by Orm proteins to prevent the toxic overaccumulation of LCBs. Here we show that overaccumulation of LCBs in yeast results in their conversion to a hitherto undescribed LCB derivative, an LCB vinyl ether. The LCB vinyl ether is predominantly formed from phytosphingosine (PHS) as revealed by conversion of odd chain length tracers C17 dihydrosphingosine and C17-PHS into the corresponding LCB vinyl ether derivative. PHS vinyl ether formation depends on ongoing acetyl-CoA synthesis, and its levels are elevated when the LCB degradative pathway is blocked by deletion of the major LCB kinase, LCB4, or the LCB phosphate lyase, DPL1. PHS vinyl ether formation thus appears to constitute a shunt for the LCB phosphate- and lyase-dependent degradation of LCBs. Consistent with a role of PHS vinyl ether formation in LCB detoxification, the lipid is efficiently exported from the cells. PMID- 27561301 TI - Ubiquitin-Conjugating Enzyme 9 Phosphorylation as a Novel Mechanism for Potentiation of the Inflammatory Response. AB - Lipopolysaccharide (LPS), a bacterial endotoxin, induces inflammation in macrophages via activation of NF-kappaB signaling. Sumoylation is a post translational modification mediated by the small ubiquitin-like modifier, SUMO. Ubiquitin-conjugating enzyme 9 (UBC9) is the only known SUMO conjugating enzyme. LPS treatment lowers SUMO-1 and UBC9 mRNA levels in primary astrocytes. UBC9 can degrade NF-kappaB inhibitor alpha (Ikbalpha) via a SUMO2/3-ubiquitin pathway. However, UBC9 may also promote Ikbalpha stability by SUMO-1 conjugation that further regulates NF-kappaB signaling. The role of UBC9 in liver inflammation is unknown. We reported that CDK1-mediated phosphorylation of UBC9 enhanced its stability. Herein, we describe an anti-inflammatory role of UBC9 that is lost when it is phosphorylated during inflammation. LPS exposure caused induction in UBC9 phosphorylation and CDK1 activation specifically in Kupffer cells in vivo and in RAW264.7 macrophages in vitro. Silencing or overexpression experiments in vitro and in vivo showed that UBC9 was required to blunt the proinflammatory response elicited by LPS. LPS stimulation raised the binding of phospho-UBC9 but not the unphosphorylated counterpart, to Ikbalpha in RAW264.7 macrophages. Hence, phospho-UBC9 may promote NF-kappaB signaling by regulating Ikbalpha and this may be a novel mechanism that deregulates liver inflammatory signaling. PMID- 27561303 TI - Correction. PMID- 27561302 TI - B4GALNT2 (GALGT2) Gene Therapy Reduces Skeletal Muscle Pathology in the FKRP P448L Mouse Model of Limb Girdle Muscular Dystrophy 2I. AB - Overexpression of B4GALNT2 (previously GALGT2) inhibits the development of muscle pathology in mouse models of Duchenne muscular dystrophy, congenital muscular dystrophy 1A, and limb girdle muscular dystrophy 2D. In these models, muscle GALGT2 overexpression induces the glycosylation of alpha dystroglycan with the cytotoxic T cell glycan and increases the overexpression of dystrophin and laminin alpha2 surrogates known to inhibit disease. Here, we show that GALGT2 gene therapy significantly reduces muscle pathology in FKRP P448Lneo(-) mice, a model for limb girdle muscular dystrophy 2I. rAAVrh74.MCK.GALGT2-treated FKRP P448Lneo(-) muscles showed reduced levels of centrally nucleated myofibers, reduced variance, increased size of myofiber diameters, reduced myofiber immunoglobulin G uptake, and reduced muscle wasting at 3 and 6 months after treatment. GALGT2 overexpression in FKRP P448Lneo(-) muscles did not cause substantial glycosylation of alpha dystroglycan with the cytotoxic T cell glycan or increased expression of dystrophin and laminin alpha2 surrogates in mature skeletal myofibers, but it increased the number of embryonic myosin-positive regenerating myofibers. These data demonstrate that GALGT2 overexpression can reduce the extent of muscle pathology in FKRP mutant muscles, but that it may do so via a mechanism that differs from its ability to induce surrogate gene expression. PMID- 27561304 TI - Commentary: Misguided Effort with Elusive Implications, and Sifting Signal from Noise with Replication Science. PMID- 27561305 TI - Erratum to: Incomplete staging surgery as a major predictor of relapse of borderline ovarian tumor. PMID- 27561306 TI - Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more? AB - BACKGROUND: Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. METHODS: A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. RESULTS: Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline's PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. CONCLUSIONS: The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV. PMID- 27561307 TI - The Effect of Social Observational Learning, Empathy and Catastrophizing in Chronic Pain Patients During Acute Pain Induction. AB - Objective: In this study, we were interested in determining whether we could alter a pain response in a chronic pain patient population by exposing participants to different videos prior to inducing acute pain. Design: This observational case series study required participants to report their pain level during the cold pressor task after viewing an instruction video. Setting: Recruitment and testing took place in a tertiary care multidisciplinary pain center. Subjects: Forty adults with chronic pain participated in the study and completed the cold pressor test. Methods: Prior to testing, questionnaires measuring pain, empathy, and catastrophic thinking were completed and participants were randomized to view an instructional video where an actress either demonstrated pain behavior or a stoic response during the cold pressor test. Results: Participants with higher levels of catastrophizing reported higher pain levels during the cold pressor test. Personal Distress Empathy measures of participants who viewed the pain catastrophizing video were significantly correlated with their final pain reports. Following the cold pressor task, participants' pain reports for their primary chronic pain sites were significantly reduced. Conclusions: These results support previous findings that people with chronic pain show the tendency toward increased acute pain experience if levels of catastrophizing and Personal Distress Empathy measures are higher. Participants reported attenuated chronic pain following induced pain, also in line with previous research suggesting a central endogenous inhibitory effect. Our findings shed light on the role of emotional and social components affecting the experience of pain in individuals with chronic pain. PMID- 27561309 TI - Driving Needed Change in Pain Education. PMID- 27561310 TI - Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia. AB - Objective: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to standardize measurement of clinically relevant patient-reported outcomes. This study evaluated the reliability and construct validity of select PROMIS static short-form (SF) instruments in women with fibromyalgia. Design: Analysis of baseline data from the Fibromyalgia Activity Study with TENS (FAST), a randomized controlled trial of the efficacy of transcutaneous electrical nerve stimulation. Setting: Dual site, university-based outpatient clinics. Subjects: Women aged 20 to 67 years diagnosed with fibromyalgia. Methods: Participants completed the Revised Fibromyalgia Impact Questionnaire (FIQR) and 10 PROMIS static SF instruments. Internal consistency was calculated using Cronbach alpha. Convergent validity was examined against the FIQR using Pearson correlation and multiple regression analysis. Results: PROMIS static SF instruments had fair to high internal consistency (Cronbach alpha = 0.58 to 0.94, P < 0.05). PROMIS 'physical function' domain score was highly correlated with FIQR 'function' score (r = -0.73). The PROMIS 'total' score was highly correlated with the FIQR total score (r = -0.72). Correlations with FIQR total score of each of the three PROMIS domain scores were r = -0.65 for 'physical function,' r = -0.63 for 'global,' and r = -0.57 for 'symptom' domain. PROMIS 'physical function,' 'global,' and 'symptom' scores explained 58% of the FIQR total score variance. Conclusions: Select PROMIS static SF instruments demonstrate convergent validity with the FIQR, a legacy measure of fibromyalgia disease severity. These results highlight the potential utility of select PROMIS static SFs for assessment and tracking of patient-reported outcomes in fibromyalgia. PMID- 27561311 TI - Socio-economic and demographic factors influencing nutritional status among early childbearing young mothers in Bangladesh. AB - BACKGROUND: Early childbearing influences women's health. This study aims to examine the effects of socio-demographic factors on nutritional status of early childbearing mothers in Bangladesh based on Body Mass Index (BMI) as the indicator. METHODS: Data was extracted from Bangladesh Demographic and Health Survey (BDHS)-2011. The survey was performed on 17,842 married women aged 15-49. We focused on early childbearing mothers (age <= 24, and who had delivered their first child <= 20). Mothers who were underweight (BMI <= 18.5 kg/m(2)) would be further classified into various grades of chronic energy deficiency (CED): mild (17.0 <= BMI < 18.5 kg/m(2)), moderate (16.0 <= BMI <17.0 kg/m(2)), and severe (BMI < 16.0 kg/m(2)). Multiple logistic regression model was used to examine the effect of socio-demographic factors on nutritional status. RESULTS: Mean age of the mothers was 20.49 +/- 2.37 years (ranged 15-24 years). The prevalence of underweight among early childbearing mothers was 32.1 % (urban 25 % and rural 35.1 %). Most of the underweight mothers had mild (62.2 %) CED, while the remaining had either moderate (25.9 %) or severe (11.9 %) CED. Multiple logistic regression analysis demonstrated that young mothers from rural areas, poor families, and those who were illiterate or with low level of education, working, and married to unemployed husband were at higher risk for being underweight. Young mothers who had non-caesarean delivered, delivered at home, or married at early age and had more than two children were also at higher risk for being underweight. CONCLUSIONS: The prevalence of underweight among early childbearing mothers in Bangladesh is very high (32.1 %), associated with the still common practice of teenage marriage. Education level, wealth index, occupation, place of residence, age at first marriage and parity were important predictors for their nutritional status. The government and non-government organizations should take initiatives to reduce the prevalence of underweight mothers in Bangladesh. PMID- 27561312 TI - Structuring evolution: biochemical networks and metabolic diversification in birds. AB - BACKGROUND: Recurrence and predictability of evolution are thought to reflect the correspondence between genomic and phenotypic dimensions of organisms, and the connectivity in deterministic networks within these dimensions. Direct examination of the correspondence between opportunities for diversification imbedded in such networks and realized diversity is illuminating, but is empirically challenging because both the deterministic networks and phenotypic diversity are modified in the course of evolution. Here we overcome this problem by directly comparing the structure of a "global" carotenoid network - comprising of all known enzymatic reactions among naturally occurring carotenoids - with the patterns of evolutionary diversification in carotenoid-producing metabolic networks utilized by birds. RESULTS: We found that phenotypic diversification in carotenoid networks across 250 species was closely associated with enzymatic connectivity of the underlying biochemical network - compounds with greater connectivity occurred the most frequently across species and were the hotspots of metabolic pathway diversification. In contrast, we found no evidence for diversification along the metabolic pathways, corroborating findings that the utilization of the global carotenoid network was not strongly influenced by history in avian evolution. CONCLUSIONS: The finding that the diversification in species-specific carotenoid networks is qualitatively predictable from the connectivity of the underlying enzymatic network points to significant structural determinism in phenotypic evolution. PMID- 27561313 TI - Validity assessment of the symptom checklist SCL-90-R and shortened versions for the general population in Ukraine. AB - BACKGROUND: The Symptom Checklist-90-Revised (SCL-90-R) is a widely used symptomatic distress questionnaire. A translated version of the SCL-90-R has been applied in Ukrainian general population surveys several times but has not yet been validated in this country. The SCL-90-R and its short versions (BSI-53, SCL 27, BSI-18, SCL-14 and SCL-9-K) were investigated in order to comparatively assess their properties and applications in Ukraine. METHODS: Secondary analysis of three nationally representative cross-sectional surveys (1997, 1999 and 2014) using SCL-90-R was applied. Two thousand sixty nine respondents participated in 2014; the sample size for the 1997 and 1999 surveys was 1810 respondents per wave. Statistical data analysis is based on calculating internal consistencies with Cronbach's Alpha, confirmatory factor analysis, nonparametric correlations and effect sizes for the equivalence of the full and short versions. RESULTS: The scales of SCL-90-R and its shortened versions showed equally high internal consistencies. With regard to factorial validity, 2014 data confirmed the dimensional structure of all versions. Unsatisfactory results were found in 1997 and 1999 for SCL-90-R and in 1997 for SCL-27, based on the Chi-square criterion (chi2/degrees of freedom > 5), though other indexes suggested satisfactory model fit (RMSEA < 0.06; CFI, TLI > 0.95). Analysis of the equivalence of shortened and full versions of the SCL-90-R has shown the presence of small effect sizes. CONCLUSION: BSI-18 and SCL-9-K are recommended for use in general population surveys as more economical versions of SCL-90-R. Both versions revealed satisfactory validity in 1997, 1999 and 2014. PMID- 27561314 TI - Impact of Resection Margin Distance on Survival of Pancreatic Cancer: A Systematic Review and Meta-Analysis. AB - PURPOSE: While curative resection is the only chance of cure in pancreatic cancer, controversies exist about the impact of surgical margin status on survival. Non-standardized pathologic report and different criteria on the R1 status made it difficult to implicate adjuvant therapy after resection based on the margin status. We evaluated the influence of resection margins on survival by meta-analysis. MATERIALS AND METHODS: We thoroughly searched electronic databases of PubMed, EMBASE, and Cochrane Library. We included studies reporting survival outcomes with different margin status: involved margin (R0 mm), margin clearance with <= 1 mm (R0-1 mm), and margin with > 1 mm (R>1 mm). Hazard ratio (HR) for overall survival was extracted, and a random-effects model was used for pooled analysis. RESULTS: A total of eight retrospective studies involving 1,932 patients were included. Pooled HR for overall survival showed that patients with R>1 mm had reduced risk of death than those with R0-1 mm (HR, 0.74; 95% confidence interval [CI], 0.61 to 0.88; p=0.001). In addition, patients with R0-1 mm had reduced risk of death than those with R0 mm (HR, 0.81; 95% CI, 0.72 to 0.91; p < 0.001). There was no heterogeneity between the included studies (I2 index, 42% and 0%; p=0.10 and p=0.82, respectively). CONCLUSION: Our results suggest that stratification of the patients based on margin status is warranted in the clinical trials assessing the role of adjuvant treatment for pancreatic cancer. PMID- 27561315 TI - Convergent validity of the interRAI-HC for societal costs estimates in comparison with the RUD Lite instrument in community dwelling older adults. AB - BACKGROUND: The interRAI-Home Care (interRAI-HC) instrument is commonly used in routine care to assess care and service needs, resource utilisation and health outcomes of community dwelling home care clients. Potentially, the interRAI-HC can also be used to calculate societal costs in economic evaluations. The purpose of this study was to assess the convergent validity of the interRAI-HC instrument in comparison with the RUD Lite instrument for the calculation of societal costs among care-dependent community dwelling older adults. METHODS: A within-subject design was used. Participants were 65 years and older and received professional community care in five countries. The RUD Lite was administered by trained (research) nurses or self-reports within 4 weeks after the interRAI-HC assessment. Agreement between the interRAI-HC and RUD Lite estimates was assessed using Spearman's correlation coefficients. We hypothesised that there was strong correlation (Spearman's rho > 0.5) between resource utilisation estimates, costs of care estimates and total societal cost estimates derived from both instruments. RESULTS: Strong correlation was found between RUD Lite and interRAI HC resource utilisation assessments for eight out of ten resource utilisation items. Total societal costs according to the RUD Lite were statistically significantly lower than according to the interRAI-HC (mean difference ?-804, 95 % CI -1340; -269). The correlation between the instruments for total societal costs and all six cost categories was strong. CONCLUSIONS: The interRAI-HC has good convergent validity as compared with the RUD-Lite instrument to estimate societal cost of resource utilisation in community dwelling older adults. Since interRAI-HC assessments are part of routine care in many community care organisations and countries already, this finding may increase the feasibility of performing economic evaluations among community dwelling older adults. PMID- 27561316 TI - How I treat essential thrombocythemia. AB - Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm that may be complicated by vascular events, including both thrombosis and bleeding. This disorder may also transform into more aggressive myeloid neoplasms, in particular into myelofibrosis. The identification of somatic mutations of JAK2, CALR, or MPL, found in about 90% of patients, has considerably improved the diagnostic approach to this disorder. Genomic profiling also holds the potential to improve prognostication and, more generally, clinical decision-making because the different driver mutations are associated with distinct clinical features. Prevention of vascular events has been so far the main objective of therapy, and continues to be extremely important in the management of patients with ET. Low dose aspirin and cytoreductive drugs can be administered to this purpose, with cytoreductive treatment being primarily given to patients at high risk of vascular complications. Currently used cytoreductive drugs include hydroxyurea, mainly used in older patients, and interferon alpha, primarily given to younger patients. There is a need for disease-modifying drugs that can eradicate clonal hematopoiesis and/or prevent progression to more aggressive myeloid neoplasms, especially in younger patients. In this article, we use a case-based discussion format to illustrate our approach to diagnosis and treatment of ET. PMID- 27561317 TI - The interaction between fibrinogen and zymogen FXIII-A2B2 is mediated by fibrinogen residues gamma390-396 and the FXIII-B subunits. AB - Coagulation transglutaminase factor XIII (FXIII) exists in circulation as heterotetrameric proenzyme FXIII-A2B2 Effectively all FXIII-A2B2 circulates bound to fibrinogen, and excess FXIII-B2 circulates in plasma. The motifs that mediate interaction of FXIII-A2B2 with fibrinogen have been elusive. We recently detected reduced binding of FXIII-A2B2 to murine fibrinogen that has gamma-chain residues 390-396 mutated to alanines (Fibgamma390-396A). Here, we evaluated binding features using human components, including recombinant fibrinogen variants, FXIII A2B2, and isolated FXIII-A2 and -B2 homodimers. FXIII-A2B2 coprecipitated with wild-type (gammaA/gammaA), alternatively-spliced (gamma'/gamma'), and alphaC truncated (Aalpha251) fibrinogens, whereas coprecipitation with human Fibgamma390 396A was reduced by 75% (P <0001). Surface plasmon resonance showed gammaA/gammaA, gamma'/gamma', and Aalpha251 fibrinogens bound FXIII-A2B2 with high affinity (nanomolar); however, Fibgamma390-396A did not bind FXIII-A2B2 These data indicate fibrinogen residues gamma390-396 comprise the major binding motif for FXIII-A2B2 Compared with gammaA/gammaA clots, FXIII-A2B2 activation peptide release was 2.7-fold slower in Fibgamma390-396A clots (P < .02). Conversely, activation of recombinant FXIII-A2 (lacking FXIII-B2) was similar in gammaA/gammaA and Fibgamma390-396A clots, suggesting fibrinogen residues gamma390 396 accelerate FXIII-A2B2 activation in a FXIII-B2-dependent mechanism. Recombinant FXIII-B2 bound gammaA/gammaA, gamma'/gamma', and Aalpha251 with similar affinities as FXIII-A2B2, but did not bind or coprecipitate with Fibgamma390-396A FXIII-B2 also coprecipitated with fibrinogen from FXIII-A deficient mouse and human plasmas. Collectively, these data indicate that FXIII A2B2 binds fibrinogen residues gamma390-396 via the B subunits, and that excess plasma FXIII-B2 is not free, but rather circulates bound to fibrinogen. These findings provide insight into assembly of the fibrinogen/FXIII-A2B2 complex in both physiologic and therapeutic situations. PMID- 27561319 TI - Design and synthesis of amorphous SiOx structures generated by Sn quantum dots: growth mechanism and luminescent origin. AB - SiOx structures with different diameters of a few hundreds of nanometers and/or a few micrometers are prepared using applied thermal evaporation. Subsequently, Sn quantum dot-based SiOx architectures are synthesized via the continuous steps of the carbothermal reduction of SnO2, substitution of Sn(4+) for In(3+), thermal oxidation of Si, Sn sublimation, interfacial reaction, and diffusion reaction consistent with corresponding phase equilibriums. Several crystalline and spherical-shaped Sn quantum dots with diameters between 2 and 7 nm are observed in the amorphous SiOx structures. The morphological evolution, including hollow Sn (or SnOx) sphere and wire-like, worm-like, tube-like, and flower-like SiOx, occurs stepwise on the Si substrate upon increasing the given process energies. The optical characteristics based on confocal measurements reveal the as synthesized SiOx structures, irrespective of whether crystallinity is formed, which all have visible-range emissions originating from the numerous different sized and -shaped Sn quantum dots permeating into the SiOx matrix. In addition, photoluminescence emissions ranging between ultraviolet and red regions are in agreement with confocal measurements. The origins of the morphology- and luminescence-controlled amorphous SiOx with Sn quantum dots are also discussed. PMID- 27561318 TI - Occupancy of human EPCR by protein C induces beta-arrestin-2 biased PAR1 signaling by both APC and thrombin. AB - Activation of protease-activated receptor 1 (PAR1) by activated protein C (APC) and thrombin elicits paradoxical cytoprotective and cytotoxic signaling responses in vascular endothelial cells through cleavage of the receptor at Arg-46 and Arg 41 protease recognition sites, respectively. It has been reported that unlike a disruptive G-protein-mediated PAR1 signaling by thrombin, APC induces a protective beta-arrestin-2 biased PAR1 signaling by unknown mechanisms. We hypothesize that the occupancy of endothelial protein C receptor (EPCR) by the Gla-domain of protein C/APC is responsible for the beta-arrestin-2 biased PAR1 signaling independent of the protease cleavage site. To test this hypothesis, we monitored the signaling specificity of thrombin in endothelial cells in response to lipopolysaccharide (LPS) with or without pretreatment of cells with protein C S195A. The PAR1-dependent recruitment of beta-arrestin-2 in response to LPS by both APC and thrombin was analyzed by functional, gene silencing, and signaling assays. Results indicate that similar to APC, thrombin exerts cytoprotective effects via beta-arrestin-2 biased PAR1 signaling. Similar to APC, thrombin triggered beta-arrestin-2-dependent recruitment of disheveled 2 (Dvl-2) in PC S195A pretreated cells. Further studies in HeLa cells transfected with PAR1 constructs revealed that EPCR occupancy initiates beta-arrestin-2 biased PAR1 signaling independent of the protease cleavage sites. We demonstrate that EPCR occupancy recruits G-protein coupled receptor kinase 5, thereby inducing beta arrestin-2 biased PAR1 signaling by both APC and thrombin. In support of a physiological relevance for these results, intraperitoneal administration of PC S195A conferred a cytoprotective effect for thrombin in an in vivo inflammatory model. PMID- 27561320 TI - Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates. AB - The rainbow trout, a carnivorous fish, displays a 'glucose-intolerant' phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely related to environmental changes and thus to metabolism adjustments governed by nutrition. In this study we first assessed in the trout liver whether and how nutritional status affects global epigenome modifications by targeting DNA methylation and histone marks previously reported to be affected in metabolic diseases. We then examined whether dietary carbohydrates could affect the epigenetic landscape of duplicated gluconeogenic genes previously reported to display changes in mRNA levels in trout fed a high carbohydrate diet. We specifically highlighted global hypomethylation of DNA and hypoacetylation of H3K9 in trout fed a HighCHO diet, a well-described phenotype in diabetes. g6pcb2 ohnologs were also hypomethylated at specific CpG sites in these animals according to their up-regulation. Our findings demonstrated that the hepatic epigenetic landscape can be affected by both nutritional status and dietary carbohydrates in trout. The mechanism underlying the setting up of these epigenetic modifications has now to be explored in order to improve understanding of its impact on the glucose intolerant phenotype in carnivorous teleosts. PMID- 27561321 TI - Prediction of Ventricular Tachycardia One Hour before Occurrence Using Artificial Neural Networks. AB - Ventricular tachycardia (VT) is a potentially fatal tachyarrhythmia, which causes a rapid heartbeat as a result of improper electrical activity of the heart. This is a potentially life-threatening arrhythmia because it can cause low blood pressure and may lead to ventricular fibrillation, asystole, and sudden cardiac death. To prevent VT, we developed an early prediction model that can predict this event one hour before its onset using an artificial neural network (ANN) generated using 14 parameters obtained from heart rate variability (HRV) and respiratory rate variability (RRV) analysis. De-identified raw data from the monitors of patients admitted to the cardiovascular intensive care unit at Asan Medical Center between September 2013 and April 2015 were collected. The dataset consisted of 52 recordings obtained one hour prior to VT events and 52 control recordings. Two-thirds of the extracted parameters were used to train the ANN, and the remaining third was used to evaluate performance of the learned ANN. The developed VT prediction model proved its performance by achieving a sensitivity of 0.88, specificity of 0.82, and AUC of 0.93. PMID- 27561322 TI - Mapping surface charge density of lipid bilayers by quantitative surface conductivity microscopy. AB - Local surface charge density of lipid membranes influences membrane-protein interactions leading to distinct functions in all living cells, and it is a vital parameter in understanding membrane-binding mechanisms, liposome design and drug delivery. Despite the significance, no method has so far been capable of mapping surface charge densities under physiologically relevant conditions. Here, we use a scanning nanopipette setup (scanning ion-conductance microscope) combined with a novel algorithm to investigate the surface conductivity near supported lipid bilayers, and we present a new approach, quantitative surface conductivity microscopy (QSCM), capable of mapping surface charge density with high quantitative precision and nanoscale resolution. The method is validated through an extensive theoretical analysis of the ionic current at the nanopipette tip, and we demonstrate the capacity of QSCM by mapping the surface charge density of model cationic, anionic and zwitterionic lipids with results accurately matching theoretical values. PMID- 27561323 TI - Scenedesmus dimorphus biofilm: Photoefficiency and biomass production under intermittent lighting. AB - This study investigated the effect of intermittent lighting on the growth performances of a Scenedesmus dimorphus biofilm. Flashing light effect (FLE) is common in traditional suspended cultures of microalgae; yet, publications about this phenomenon, in the context of biofilm cultivation, are scarce. In this work we demonstrate that, thanks to intermittent illumination, it is possible for attached cultivations to fulfill FLE, improve photoefficiency and productivity as well as providing protection from photoinhibition using much lower flashing light frequencies than those usually required with suspended cultures. Medium frequency intermittent lighting (0.1 Hz) guaranteed excellent light integration resulting in 9.13 g m(-2) d(-1) biomass productivity, which was 8.9% higher than with continuous lighting. Results showed that a light fraction value of 0.5 always improved photoefficiency values as related to continuous light with a 118.8% maximum increase. PMID- 27561324 TI - Corrigendum: CRISPR/Cas9-Mediated Immunity to Geminiviruses: Differential Interference and Evasion. PMID- 27561325 TI - Particle Size Controls on Water Adsorption and Condensation Regimes at Mineral Surfaces. AB - Atmospheric water vapour interacting with hydrophilic mineral surfaces can produce water films of various thicknesses and structures. In this work we show that mineral particle size controls water loadings achieved by water vapour deposition on 21 contrasting mineral samples exposed to atmospheres of up to ~16 Torr water (70% relative humidity at 25 degrees C). Submicrometer-sized particles hosted up to ~5 monolayers of water, while micrometer-sized particles up to several thousand monolayers. All films exhibited vibrational spectroscopic signals akin to liquid water, yet with a disrupted network of hydrogen bonds. Water adsorption isotherms were predicted using models (1- or 2- term Freundlich and Do-Do models) describing an adsorption and a condensation regime, respectively pertaining to the binding of water onto mineral surfaces and water film growth by water-water interactions. The Hygroscopic Growth Theory could also account for the particle size dependence on condensable water loadings under the premise that larger particles have a greater propensity of exhibiting of surface regions and interparticle spacings facilitating water condensation reactions. Our work should impact our ability to predict water film formation at mineral surfaces of contrasting particle sizes, and should thus contribute to our understanding of water adsorption and condensation reactions occuring in nature. PMID- 27561327 TI - s+/- pairing near a Lifshitz transition. AB - Observations of robust superconductivity in some of the iron based superconductors in the vicinity of a Lifshitz point where a spin density wave instability is suppressed as the hole band drops below the Fermi energy raise questions for spin-fluctuation theories. Here we discuss spin-fluctuation pairing for a bilayer Hubbard model, which goes through such a Lifshitz transition. We find s+/- pairing with a transition temperature that peaks beyond the Lifshitz point and a gap function that has essentially the same magnitude but opposite sign on the incipient hole band as it does on the electron band that has a Fermi surface. PMID- 27561326 TI - Hypersensitivity to DNA damage in antephase as a safeguard for genome stability. AB - Activation of the DNA-damage response can lead to the induction of an arrest at various stages in the cell cycle. These arrests are reversible in nature, unless the damage is too excessive. Here we find that checkpoint reversibility is lost in cells that are in very late G2, but not yet fully committed to enter mitosis (antephase). We show that antephase cells exit the cell cycle and enter senescence at levels of DNA damage that induce a reversible arrest in early G2. We show that checkpoint reversibility critically depends on the presence of the APC/C inhibitor Emi1, which is degraded just before mitosis. Importantly, ablation of the cell cycle withdrawal mechanism in antephase promotes cell division in the presence of broken chromosomes. Thus, our data uncover a novel, but irreversible, DNA-damage response in antephase that is required to prevent the propagation of DNA damage during cell division. PMID- 27561328 TI - Patterned FeNi soft magnetic strips film with tunable resonance frequency from 1 to 10.6 GHz. AB - Soft magnetic films with a wide-range tunable ferromagnetic resonance frequency are suitable for miniaturization and multifunctionalization of microwave integrated circuits. Fabrication of these films for high-frequency applications is usually complicated and difficult. We demonstrate a simple method to fabricate patterned FeNi soft magnetic strip films by magnetron sputtering and photolithography. Films prepared by this method exhibits a tunable in-plane uniaxial magnetic anisotropy (IPUMA) for different strip widths and gaps. As the strip widths changing from 500 to 2 MUm, the IPUMA field increases monotonically from 2.2 to 576 Oe and resonance frequency from 1 to 10.6 GHz(which covers four microwave bands, including the L,S,C and X bands) respectively. This ultra-wide range adjustability of resonance frequency can be attributed to shape anisotropy of strips. Considering that FeNi alloy has relatively low magnetocrystalline anisotropy, so a wider adjustable range of resonance frequency could be obtained using materials with stronger magnetocrystalline anisotropy. PMID- 27561329 TI - Invasive ductal carcinoma of the breast with osteoclast-like giant cells and clear cell features: a case report of a novel finding and review of the literature. AB - BACKGROUND: Osteoclast-like giant cells (OLGCs) are a rare histologic finding within a tumor of the breast. Although there has been discussion as to the pathogenesis and prognosis related to this finding, our understanding of its significance remains inconclusive. Clear cells are another unique histologic finding in breast tumors and are typically associated with tumors arising in other organs such as renal cell carcinoma. CASE PRESENTATION: This is a case report of a 64-year-old female who presented with one tumor identified as invasive ductal carcinoma with a combination of OLGCs and clear cell features. CONCLUSIONS: To our knowledge, this combination of findings has not been previously described in the literature and therefore represents another morphologic manifestation of breast carcinoma. As patients are diagnosed earlier and live longer, a growing number of these rare variants may be recognized and provide opportunities to further our understanding of the associated molecular pathways which could contribute to the possibility of therapeutic intervention. PMID- 27561330 TI - Socially cued developmental plasticity in web-building spiders. AB - BACKGROUND: Socially cued anticipatory plasticity (SCAP) has been proposed as a widespread mechanism of adaptive life-history shifts in semelparous species with extreme male mating investment. Such mating systems evolved several times independently in spiders and male reproductive success should critically depend on timely maturation and rapid location of a receptive and, ideally, virgin female. We experimentally investigated socially cued anticipatory plasticity in two sympatric, closely related Nephila species that share many components of their mating systems, but differ in the degree to which male reproductive success depends on mating with virgin females. Juveniles of both species were reared either in the presence or absence of virgin female silk cues. We predicted strong selection on socially cued plasticity in N. fenestrata in which males follow a highly specialized terminal investment strategy, but expected a weaker plastic response in N. senegalensis in which males lost the ability to monopolize females. RESULTS: Contrary to our predictions, N. fenestrata males presented with virgin female silk cues did not mature earlier than siblings reared isolated from such cues. Males in N. senegalensis, however, showed a significant response to female cues and matured several days earlier than control males. Plastic adjustment of maturation had no effect on male size. CONCLUSIONS: Our results indicate that a strong benefit of mating with virgins due to first male sperm priority does not necessarily promote socially cued anticipatory plasticity. We emphasize the bidirectional mode of developmental responses and suggest that this form of plasticity may not only yield benefits through accelerated maturation, but also by avoiding costs of precipitate maturation in the absence of female cues. PMID- 27561331 TI - Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking? AB - BACKGROUND: Bacterial meningitis is associated with significant morbidity and mortality despite advances in medical care. The main objective of this study was to assess the association of adjunctive dexamethasone treatment with discharge outcome of patients treated as bacterial meningitis in low income setting. METHODS: A retrospective study was conducted at four teaching hospitals across Ethiopia. Patients of age 14 years and older treated as cases of bacterial meningitis between January 1, 2011 and April 30, 2015 were included in this study. Information regarding sociodemographic data, clinical presentations, laboratory data, treatments given and status at hospital discharge were retrieved from patients' medical records using a structured questionnaire. Predefined outcome variables at discharge were analysed using descriptive statistics. Multivariable logistic regression was used to identify factors independently associated with poor outcome. RESULTS: A total of 425 patients treated with the presumptive clinical diagnosis of bacterial meningitis were included in this study (lumbar puncture done in 56 %; only 19 % had CSF findings compatible with bacterial meningitis, and only 3 % had proven etiology). The overall in hospital mortality rate was 20.2 %. Impaired consciousness, aspiration pneumonia, and cranial nerve palsy at admission were independently associated with increased mortality. Adjuvant dexamethasone, which was used in 50.4 % of patients, was associated with increased in-hospital mortality (AOR = 3.38; 95 % CI 1.87-6.12, p < 0.001) and low Glasgow outcome scale (GOS) at discharge (AOR = 4.46 (95 % CI 1.98-10.08). This association between dexamethasone and unfavorable outcome was found to be more pronounced in suspected but unproven cases and in those without CSF alterations compatible with bacterial meningitis. CONCLUSION: Most patients treated for suspected bacterial meningitis did not receive proper diagnostic workup. Adjuvant dexamethasone use in clinically suspected but unproven cases of bacterial meningitis was associated with an increased mortality and poor discharge GOS. These findings show that there are potential deleterious effects in unconfirmed cases in this setting. Physicians practising under such circumstances should thus abide with the current recommendation and defer the use of adjuvant corticosteroid in suspected cases of bacterial meningitis. PMID- 27561332 TI - Why do marital partners of people living with HIV not test for HIV? A qualitative study in Lusaka, Zambia. AB - BACKGROUND: Knowledge of HIV status is crucial for HIV prevention and management in marital relationships. Yet some marital partners of people living with HIV decline HIV testing despite knowing the HIV-positive status of their partners. To date, little research has explored the reasons for this. METHODS: An exploratory qualitative study was undertaken in Lusaka, Zambia, between March 2010 and September 2011, nested within a larger ethnographic study. In-depth interviews were held with individuals who knew the HIV-positive status of their marital partners but never sought HIV testing (n = 30) and HIV service providers of a public sector clinic (n = 10). A focus group discussion was also conducted with eight (8) lay HIV counsellors. Data was transcribed, coded and managed using ATLAS.ti and analysed using latent content analysis. RESULTS: The overarching barrier to uptake of HIV testing was study participants' perception of their physical health, reinforced by uptake of herbal remedies and conventional non-HIV medication to mitigate perceived HIV-related symptoms. They indicated willingness to test for HIV if they noticed a decline in physical health and other alternative forms of care became ineffective. Also, some study participants viewed themselves as already infected with HIV on account of the HIV-positive status of their marital partners, with some opting for faith healing to get 'cured'. Other barriers were the perceived psychological burden of living with HIV, modulated by lay belief that knowledge of HIV-positive status led to rapid physical deterioration of health. Perceived inability to sustain uptake of life long treatment - influenced by a negative attitude towards treatment - further undermined uptake of HIV testing. Self-stigma, which manifested itself through fear of blame and a need to maintain moral credibility in marital relationships, also undermined uptake of HIV testing. CONCLUSIONS: Improving uptake of HIV testing requires a multi-pronged approach that addresses self-stigma, lay risk perceptions, negative treatment and health beliefs and the perceived psychological burden of living with HIV. Strengthening couple HIV testing services, including addressing conflict and addressing gendered power relationships are also warranted to facilitate joint knowledge, acceptance and management of HIV status in marital relationships. PMID- 27561334 TI - Parameter estimation without confidence intervals? PMID- 27561333 TI - In vitro organo-protective effect of bark extracts from Syzygium guineense var macrocarpum against ferric-nitrilotriacetate-induced stress in wistar rats homogenates. AB - BACKGROUND: Overconsumption of oxygen in mammalian cells often lead to the production of reactive oxygen species (ROS) resulting from different mechanisms. Escape of scavenging enzymes/components or nutritional failure are the most important origins. Plant-derived molecules may protect biological molecules either by quenching free radicals, delaying or preventing the ROS formation or by restoring antioxidant enzymes activities. The present study assessed the antioxidant, phenolic profile and protective effect of barks extracts of Syzyguim guineense var macrocarpum against ferric nitriloacetate-induced stress in the liver, heart kidney and brain tissues of wistar rat homogenates. METHODS: Three extracts (aqueous, ethanol and aqueous-ethanol) from the barks of S. guineense var macrocarpum were used in this study. The spectrophotometric standardized methods were used to determine the free radical scavenging and antioxidant potential of the extracts. The protective properties of these plant extracts were also investigated as well as the quantification of secondary metabolites content (total phenolic, flavonoids and flavonols content). The HPLC method helped for characterizing phenolic compounds present in these extracts. RESULTS AND DISCUSSION: All the extracts exhibited a free radical scavenging potential in a concentration dependent manner which varied from 15.18 +/- 0.80 to 97.15 +/- 0.71 % depending to the type of extract and the method used. The ethanol extract had the higher phenolic content (432.85 mg QE/g extract), including total flavonoids (961.66 mg QE/g extract) and flavonols content (25.12 mg QE/g extract) and higher total antioxidant capacity. Among the phenolic compounds present in the extracts, the HLPC profile revealed the presence of syringic acid and apigenin in all the extracts. The extracts demonstrated their protective effect mostly in liver and brain homogenates by delaying or preventing lipid peroxidation, restoring enzymatic activities and enhancing glutathione levels. CONCLUSION: The overall results demonstrated that the extracts exhibited significant antioxidant and protective effects in liver and brain liver homogenates. PMID- 27561335 TI - Establishment and application of a competitive enzyme-linked immunosorbent assay differentiating PCV2 antibodies from mixture of PCV1/PCV2 antibodies in pig sera. AB - BACKGROUND: Porcine cirovirus type 1 (PCV1) and type 2 (PCV2) are circulating in Chinese pig herds and the infected pigs develop antibodies to both viruses. Current commercial available ELISA kits cannot differentiate PCV2-specific antibodies from the mixtures of PCV1 and PCV2 antibodies in PCV1/2-infected or PCV2-vaccinated pigs. Therefore, the need for developing PCV2-specific ELISA methods is urgent to evaluate PCV2 antibody level in exclusion of PCV1 antibody interference after PCV2 vaccination. RESULTS: Virus-like particles (VLPs) of PCV2 based on the recombinant Cap protein were expressed in Escherichia coli. A competing ELISA was established by using the VLPs as coating antigen and a PCV2 specific monoclonal antibody as the competing antibody. The competing ELISA was compared with the results obtained by using an immunoperoxidase monolayer assay on 160 serum samples. The sensitivity and specificity of this competing ELISA were determined as 96.5 and 96.0 %, at 2 standard deviation from the mean or 91.8 and 100 % at 3 standard deviations from the mean. Next, a serological survey of 1297 vaccinated serum samples collected from commercial pig herds in Beijing, Hunan and Henan provinces in China was conducted. The results showed that 85.9 % of sera having positive PCV2 antibodies. CONCLUSIONS: The competing ELISA we developed in this study was both sensitive and specific to PCV2 and was suitable for large-scale PCV2 antibody monitoring in exclusion of PCV1 antibody interference after PCV2 vaccination. PMID- 27561336 TI - Evaluation of a trauma team activation protocol revision: a prospective cohort study. AB - BACKGROUND: Correct triage based on prehospital information contributes to a better outcome for potentially seriously injured patients. In 2011 we changed the trauma team activation (TTA) criteria in our center in order to improve the high over- and undertriage properties of the protocol. Five criteria that were unable to predict severe injury were removed. In the present study, we evaluated the protocol revision by comparing over- and undertriage in the former and present set of criteria. METHODS: All severely injured patients (Injury Severity Score (ISS) > 15) and all patients admitted with TTA in the period of 01.01.2013 - 31.12.2014 were included in the study. We defined overtriage as the fraction of patients with TTA when ISS <=15 and undertriage as the fraction of patients without TTA when ISS > 15. We also evaluated triage with the occurrence of emergency procedures immediately after admission. RESULTS: 324 patients were included, 164 patients had ISS>15, 287 were admitted with TTA. Over- and undertriage were 74 % and 28 % respectively. When we used emergency procedure as reference, the figures were 83 % and 15 % respectively. Undertriaged patients had significantly more neurosurgical injuries and were significantly more often transferred from an acute care hospital. DISCUSSION: Over- and undertriage are almost the same as before the criteria were revised, and higher thanrecommended levels. CONCLUSIONS: Revision of the TTA criteria has not improved triage, and further measures are necessary to achieveacceptable levels. PMID- 27561338 TI - The optical measurement of large cluster tracks in a gas jet. AB - We propose an optical method based on Rayleigh scattering for the direct measurement of cluster tracks produced by a high-pressure gas jet. The tracks of the argon and methane clusters are acquired by a high-speed camera. It is found that the cluster sizes of these tracks are within the range of 7E + 03~1E + 07 for argon and 2E + 06~4E + 08 for methane. Most argon tracks are continuous and their intensity changes gradually, while the majority of the methane tracks are separated into discrete fractions and their intensity alters periodically along the flight path, which may indicate the methane clusters are more unstable and easily to break up. Special methane clusters which may fly at an axial velocity of less than 2.5m/s are also found. This method is very sensitive to large gas cluster and has broad application prospects in cluster physics. PMID- 27561339 TI - [The expanding concept of CKD-MBD]. AB - Almost seven years have passed since the publication of the KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder(CKD-MBD). During this period, several new medications for osteoporosis that may be applicable to patients with CKD have become available. Clinical studies have also shown the utility of bone mineral density to assess fracture risk in CKD. These new data charges us with the task of reconciling the concept of renal osteodystrophy(ROD)and osteoporosis in CKD. This review summarize the recent advances in the management of bone disease in CKD and the key points raised during the discussion for the KDIGO guideline revision, and address the problems to be solved in future. PMID- 27561337 TI - Effects of IL-1beta, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. AB - Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1beta, IL-6 and IL 8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot formation, erythrocyte pathology and platelet hyper-activation, and these three cytokines have known receptors on platelets. Although these cytokines are always unregulated in inflammation, we do not know how the individual cytokines act upon the structure of erythrocytes and platelets, and which of the viscoelastic clot parameters are changed. Here we study the effects of IL-1beta, IL-6 and IL-8 at low physiological levels, representative of chronic inflammation, by using scanning electron microscopy and thromboelastography. All three interleukins caused the viscoelastic properties to display an increased hypercoagulability of whole blood and pathology of both erythrocytes and platelets. The most pronounced changes were noted where all three cytokines caused platelet hyper-activation and spreading. Erythrocyte structure was notably affected in the presence of IL-8, where the morphological changes resembled that typically seen in eryptosis (programmed cell death). We suggest that erythrocytes and platelets are particularly sensitive to cytokine presence, and that they are excellent health indicators. PMID- 27561340 TI - [Bone turnover and mineralization in patients with kidney failure]. AB - Bone remodeling is a device to accomplish "the buffering of the extracellular fluid mineral", which is one of the two major physiological functions of bone. Bone turnover is a term to express the frequency of bone remodeling, and its last step is calcification. When remodeling is induced, at first a large amount of mineral is released from bone to extracellular fluid transiently, and thereafter mineral is slowly and steadily drawn into bone. The extracellular minerals, especially calcium, are maintained by this repetition. When kidney is injured, bone turnover takes a wide spectrum from remarkably high cases to low cases. Primary calcification also shows marked individual differences. The classic renal bone diseases 5 classification clearly categorizes these disease condition, which is synonymous with renal osteodystrophy today. PMID- 27561341 TI - [Clinical evaluation for abnormalities of bone and mineral metabolism in ESKD]. AB - In patients with end-stage kidney disease(ESKD), bone disorders are characterized by cortical porosity and by abnormal turnover of bone metabolism:adynamic(low turnover)bone disease and high turnover bone due to various degrees of secondary hyperparathyroidism. Abnormalities of bone metabolism are generally assessed by interview, X-ray, bone mineral density(BMD), serum phosphorus, calcium, and parathyroid hormone levels, and bone metabolic markers. Recent clinical studies have demonstrated that high turnover bone representing elevated bone metabolic markers and low BMD are independent risks of bone fractures as well as mortality among this population. Treatment of bone disorders in ESKD patients should be aiming at the normalization of mineral metabolism and the maintenance and/or improvement of BMD. PMID- 27561342 TI - [Point of note in the treatment of osteoporotic patients complicated with chronic kidney disease]. AB - Chronic kidney disease causes secondary hyperparathyroidism due to an accumulation of phosphate in the circulation, resulting in the development of CKD mineral bone disease(MBD), which increases the risk of cardiovascular disease and fracture. Increase of bone fracture in CKD might be explained by phosphate overload, increased oxidative stress, malnutrition, and the increased risk of fall due to sarcopenia. It is recently emphasized that the overtreatment of osteoporosis might induce the development of adynamic bone disease by calcium overload and/or oversuppression of bone turnover, which might stimulate ectopic calcification including vessel wall. Considering for the high prevalence of CKD in elderly osteoporotic women, we should be careful to avoid the induction of calcium/phosphate overload and over-suppression of bone turnover when we treat osteoporosis for such patients. PMID- 27561343 TI - [Several factors related with bone quality abnormalities exist in patients with renal failure]. AB - Recently, several papers revealed that bone pathophysiological abnormalities related with end-stage renal disease(ESRD)contain a multiplicity of injured bone quality. Although deteriorated bone quality in ESRD patients is understood as a risk factor of fracture in these patients, actual conditions still remain unclear. Here, I will provide a short review on both the deteriorated bone quality in ESRD patients and animal models, and also specific conditions which is providing abnormality. I also will discuss the problem points of abnormal bone quality in ESRD patients. PMID- 27561344 TI - [Is it possible to-predict fracture in CKD patients?]. AB - Routine examination of bone mineral density(BMD)by DXA(dual energy X-ray absorptiometry)is useful to predict bone fracture in both CKD nondialysis and dialysis patients. The cutoff value of BMD to predict bone fracture is different between genders and its predictive power is better in patients with lower serum PTH levels than higher counterpart. Increase in serum bone specific alkaline phosphatase is a better predictor of the bone fracture than serum PTH levels. PMID- 27561345 TI - [Teriparatide:benefit and safety for bone disease in CKD patients undergoing hemodialysis]. AB - Teriparatide, 1-34 parathyroid hormone, is one of effective treatments for osteoporosis. Teriparatide shows an anabolic effect for bone formation, as a result, increases bone mineral density as well as prevention of fractures in the general population. On the other hand, there are a few report about the effect of teriparatide on increase of bone mineral density in maintenance hemodialysis patients. In addition to CKD-MBD, osteoporosis is also an important pathological change in ESRD patients, therefore its safety and efficacy should be discussed in more detail. PMID- 27561346 TI - [Is denosmab really effective and safe in the care of CKD-MBD?]. AB - The authors of Freedom study enrolling primary osteoporosis patients argued that the anti-fracture effect of denosmab is not dependent on baseline estimated glomerular filtration rate(eGFR)by showing the non-significant interaction term between treatment and CKD stage. However, given disproportionate numbers of patients in each subgroup(4069, 2817, and only 73 patients, in CKD stage 2, 3, and, 4, respectively), this study seems to lack the statistical power to reach a definite conclusion on the effect modification by CKD stage. Truly, the serum concentration of infused denosmab in patients with CKD stage 4 is equivalent to that in patients without CKD, the risk of developing life-threatening or prolonged hypocalcemia is huge even under active vitamin D therapy in this population. In hemodialysis patients, this drug is relatively safer because each dialysis session delivers calcium into the circulation 3 times a week. However, even with concomitant administration of massive active vitamin D, the increase of intact PTH levels greater than 1000 pg/mL by this agent is not rare. In other words, this drug worsens secondary hyperparathyroidism. Moreover, reportedly, calcium and active vitamin D administered to avoid hypocalcemia can lead to ectopic calcification especially under the low bone turnover induced by this agent. In fact, transient hypercalcemia often follows hypocalcemia by the inevitable calcium supplementation. PMID- 27561347 TI - [The efficacy and safety of bisphosphonate for patients with kidney disease]. AB - Bisphoshonate is largely used for treatment of osteoporosis in general population. The gastrointestinal absorption is poor and it can be excreted via only kidney. Therefore, CKD patients can accumulate a higher dose of bisphosphonate in their body. Although the primary action of bisphosphonate is the inhibition of bone resorption, it secondary suppresses bone formation, which can often lead to adynamic bone disease in patients with CKD. In CKD patients who still have normal parathyroid hormone, calcium, and phosphate levels, randomized trials showed the similar effects as in non-CKD patients;however, in patients with CKD stage 4 and dialysis patients, data are very limited and the benefits and safety has remained unclear. In several small clinical researches, etidronate has reduced vessel calcifications, but this has not been yet proved in a large randomized study. PMID- 27561348 TI - [Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease]. AB - Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs may be used in unique osteoporosis drugs for reducing the incidence and progression of breast cancer. Moreover, SERMs attenuate oxidative stress and may lessen the deterioration of kidney function in patients with chronic kidney disease. The evidences for the efficacy and safety of SERMs in patients with advanced chronic kidney disease are insufficient, and knowledge concerning the selection and indication of osteoporosis drugs for those patients need to be developed. PMID- 27561349 TI - [The efficacy and safety of activated vitamin D for CKD-MBD]. AB - Metabolic bone disorders that are represented by secondary hyperparathyroidism occur with the progression of chronic kidney disease(CKD). The administration of activated vitamin D is expected to improve high-turnover bone disorders and is widely used for the management of bone mineral diseases in patients with CKD and end-stage renal disease. CKD is an underlying disease of secondary osteoporosis and coexists with primary osteoporosis at a high rate. With regard to osteoporosis patients with renal insufficiency, the administration of activated vitamin D is also thought to reduce the fracture incidence by both increasing bone mass and reducing falls. PMID- 27561350 TI - Facile synthesis of diverse graphene nanomeshes based on simultaneous regulation of pore size and surface structure. AB - Recently, graphene nanomesh (GNM) has attracted great attentions due to its unique porous structure, abundant active sites, finite band gap and possesses potential applications in the fields of electronics, gas sensor/storage, catalysis, etc. Therefore, diverse GNMs with different physical and chemical properties are required urgently to meet different applications. Herein we demonstrate a facile synthetic method based on the famous Fenton reaction to prepare GNM, by using economically fabricated graphene oxide (GO) as a starting material. By precisely controlling the reaction time, simultaneous regulation of pore size from 2.9 to 11.1 nm and surface structure can be realized. Ultimately, diverse GNMs with tunable band gap and work function can be obtained. Specially, the band gap decreases from 4.5-2.3 eV for GO, which is an insulator, to 3.9-1.24 eV for GNM-5 h, which approaches to a semiconductor. The dual nature of electrophilic addition and oxidizability of HO(*) is responsible for this controllable synthesis. This efficient, low-cost, inherently scalable synthetic method is suitable for provide diverse and optional GNMs, and may be generalized to a universal technique. PMID- 27561351 TI - Prediction of allosteric sites and mediating interactions through bond-to-bond propensities. AB - Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID- 27561352 TI - Erratum: Cell culture-derived HCV cannot infect synovial fibroblasts. PMID- 27561354 TI - Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA end resection. AB - Human CtIP is a decisive factor in DNA double-strand break repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of DNA-end resection, CtIP function is tightly controlled by multiple protein-protein interactions and post-translational modifications. Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. A tripeptide motif (FRY) conserved across vertebrate CtIP proteins is essential for KLHL15-binding; its mutation blocks KLHL15-dependent CtIP ubiquitination and degradation. Consequently, DNA-end resection is strongly attenuated in cells overexpressing KLHL15 but amplified in cells either expressing a CtIP-FRY mutant or lacking KLHL15, thus impacting the balance between HR and NHEJ. Collectively, our findings underline the key importance and high complexity of CtIP modulation for genome integrity. PMID- 27561353 TI - Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation. AB - The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0-40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments. PMID- 27561355 TI - Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis. AB - Newly formed microcapillary networks arising in adult organisms by angiogenic and inflammatory stimuli contribute to pathologies such as corneal and retinal blindness, tumor growth, and metastasis. Therapeutic inhibition of pathologic angiogenesis has focused on targeting the VEGF pathway, while comparatively little attention has been given to remodeling of the new microcapillaries into a stabilized, functional, and persistent vascular network. Here, we used a novel reversible model of inflammatory angiogenesis in the rat cornea to investigate endogenous factors rapidly invoked to remodel, normalize and regress microcapillaries as part of the natural response to regain corneal avascularity. Rapid reversal of an inflammatory angiogenic stimulus suppressed granulocytic activity, enhanced recruitment of remodelling macrophages, induced capillary intussusception, and enriched pathways and processes involving immune cells, chemokines, morphogenesis, axonal guidance, and cell motility, adhesion, and cytoskeletal functions. Whole transcriptome gene expression analysis revealed suppression of numerous inflammatory and angiogenic factors and enhancement of endogenous inhibitors. Many of the identified genes function independently of VEGF and represent potentially new targets for molecular control of the critical process of microvascular remodeling and regression in the cornea. PMID- 27561356 TI - Comparative Proteomic Analysis of Buffalo Oocytes Matured in vitro Using iTRAQ Technique. AB - To investigate the protein profiling of buffalo oocytes at the germinal vesicle (GV) stage and metaphase II (MII) stage, an iTRAQ-based strategy was applied. A total of 3,763 proteins were identified, which representing the largest buffalo oocytes proteome dataset to date. Among these proteins identified, 173 proteins were differentially expressed in GV oocytes and competent MII oocytes, and 146 proteins were differentially abundant in competent and incompetent matured oocytes. Functional and KEGG pathway analysis revealed that the up-regulated proteins in competent MII oocytes were related to chromosome segregation, microtubule-based process, protein transport, oxidation reduction, ribosome, and oxidative phosphorylation, etc., in comparison with GV and incompetent MII oocytes. This is the first proteomic report on buffalo oocytes from different maturation stages and developmental competent status. These data will provide valuable information for understanding the molecular mechanism underlying buffalo oocyte maturation, and these proteins may potentially act as markers to predict developmental competence of buffalo oocyte during in vitro maturation. PMID- 27561357 TI - A 5-year longitudinal analysis of modifiable predictors for outdoor play and screen-time of 2- to 5-year-olds. AB - BACKGROUND: Early childhood is a critical time for establishing physical activity and sedentary behaviours. Identifying modifiable predictors of physical activity and sedentary behaviours in the early life stages can inform the development of early intervention programs. The aim of this study was to identify modifiable predictors of outdoor play (a proxy of physical activity) and screen-time in 2- to 5-year-olds. METHODS: A longitudinal data analysis was conducted using 5-year follow-up data from the Healthy Beginnings Trial undertaken in Sydney, Australia from 2007 to 2013. A total of 667 pregnant women were recruited for the study. Information on mothers' demographics, physical activity, screen-time, knowledge of child development, and awareness of childhood obesity during pregnancy (at baseline); children's tummy time (a colloquial term describing the time when a baby is placed on his or her stomach while awake and supervised) at 6 months old and screen-time at 1 year old was collected via interviews with participating mothers as potential modifiable predictors. Main outcomes were children's outdoor playtime and screen-time at ages 2, 3.5, and 5 years. Mixed linear and logistic regression models were built to determine these modifiable predictors. RESULTS: Mothers' screen-time during pregnancy (beta = 2.1, 95 % CI 0.17-4.12; P = 0.030) and children's daily screen-time at age 1 year (beta = 15.2, 95 % CI 7.28-23.11; P < 0.0001) predicted children's daily screen-time across ages 2 to 5 years after controlling for confounding factors. Practising tummy time daily (beta = 13.4, 95 % CI 1.26-25.52; P = 0.030), mother's physical activity level (beta = 3.9, 95 % CI 0.46-7.28; P = 0.026), and having been informed about playing with child at baseline (beta = 11.6, 95 % CI 1.56-21.54; P = 0.023) predicted children's outdoor playtime across ages 2 to 5 years. CONCLUSIONS: Mothers played an important role in their children's outdoor play and screen-time in the first years of live. Children's early exposure to screen devices could be associated with their later screen-time. Early interventions to improve young children's physical activity and sedentary behaviour should focus on improving pregnant women's physical activity, awareness of playing with their child, reducing their own screen-time as well as practicing daily tummy time for infants after giving birth. TRIAL REGISTRATION: The Healthy Beginnings Trial is registered with the Australian Clinical Trial Registry ( ACTRNO12607000168459 ). Registered 13 March 2007. Prospectively registered. PMID- 27561359 TI - Perceptions and understandings of pregnancy, antenatal care and postpartum care among rural Lao women and their families. AB - BACKGROUND: Lao People's Democratic Republic (Lao PDR) has the highest maternal mortality rate (MMR) and infant mortality rate (IMR) due to traditional practice and beliefs on pregnancy, delivery and postpartum. The objective of this study was to get a better understanding of cultural beliefs and practices surrounding pregnancy, ANC and postpartum care among rural women in Lao PDR. METHODS: Eight focus group discussions and 52 interviews were carried out with delivered women, husbands, mothers, traditional birth attendants, head villagers, Lao Women's Union members and healthcare workers, in Khammouane and Champasack provinces in Lao PDR. In order to accurately grasp participants' perceptions and understandings, content analysis was used to analyze the transcripts. RESULTS: Most women in the study claimed to have attended ANC, but participants also explained that it was unnecessary to attend ANC and give birth at a clinic if the woman felt healthy. Factors that discouraged ANC attendance and giving birth at clinics included: time and money constraints; the perceived necessity of giving birth on a "hot bed"; the need for "mother-roasting" after giving birth; the belief that preparing for a birth was a bad omen for the birth; the belief that colostrum is unhealthy for the newborn child; and the preference for cutting the umbilical cord with a piece of sharpened bamboo. CONCLUSIONS: Harmful cultural practices such as discarding colostrum should be discouraged; beneficial practices such as family involvement in birthing and keeping a mother warm after birth could be integrated into biomedical practice. Given the prevalence and importance of the cultural understandings we have described in this study, it is clear that proposed changes in cultural practices need to be addressed with sensitivity and that community stakeholders and trusted leaders will need to be involved. PMID- 27561360 TI - Antimycobacterial Metabolites from Marine Invertebrates. AB - Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. PMID- 27561358 TI - OGS2: genome re-annotation of the jewel wasp Nasonia vitripennis. AB - BACKGROUND: Nasonia vitripennis is an emerging insect model system with haplodiploid genetics. It holds a key position within the insect phylogeny for comparative, evolutionary and behavioral genetic studies. The draft genomes for N. vitripennis and two sibling species were published in 2010, yet a considerable amount of transcriptiome data have since been produced thereby enabling improvements to the original (OGS1.2) annotated gene set. We describe and apply the EvidentialGene method used to produce an updated gene set (OGS2). We also carry out comparative analyses showcasing the usefulness of the revised annotated gene set. RESULTS: The revised annotation (OGS2) now consists of 24,388 genes with supporting evidence, compared to 18,850 for OGS1.2. Improvements include the nearly complete annotation of untranslated regions (UTR) for 97 % of the genes compared to 28 % of genes for OGS1.2. The fraction of RNA-Seq validated introns also grow from 85 to 98 % in this latest gene set. The EST and RNA-Seq expression data provide support for several non-protein coding loci and 7712 alternative transcripts for 4146 genes. Notably, we report 180 alternative transcripts for the gene lola. Nasonia now has among the most complete insect gene set; only 27 conserved single copy orthologs in arthropods are missing from OGS2. Its genome also contains 2.1-fold more duplicated genes and 1.4-fold more single copy genes than the Drosophila melanogaster genome. The Nasonia gene count is larger than those of other sequenced hymenopteran species, owing both to improvements in the genome annotation and to unique genes in the wasp lineage. We identify 1008 genes and 171 gene families that deviate significantly from other hymenopterans in their rates of protein evolution and duplication history, respectively. We also provide an analysis of alternative splicing that reveals that genes with no annotated isoforms are characterized by shorter transcripts, fewer introns, faster protein evolution and higher probabilities of duplication than genes having alternative transcripts. CONCLUSIONS: Genome-wide expression data greatly improves the annotation of the N. vitripennis genome, by increasing the gene count, reducing the number of missing genes and providing more comprehensive data on splicing and gene structure. The improved gene set identifies lineage-specific genomic features tied to Nasonia's biology, as well as numerous novel genes. OGS2 and its associated search tools are available at http://arthropods.eugenes.org/EvidentialGene/nasonia/ , www.hymenopteragenome.org/nasonia/ and waspAtlas: www.tinyURL.com/waspAtlas . The EvidentialGene pipeline is available at https://sourceforge.net/projects/evidentialgene/ . PMID- 27561361 TI - Erratum to: Notch1 hallmarks fibrillary depositions in sporadic Alzheimer's disease. PMID- 27561362 TI - From paradigm shift towards ovarian cancer prevention. PMID- 27561363 TI - Co-infections and environmental conditions drive the distributions of blood parasites in wild birds. AB - Experimental work increasingly suggests that non-random pathogen associations can affect the spread or severity of disease. Yet due to difficulties distinguishing and interpreting co-infections, evidence for the presence and directionality of pathogen co-occurrences in wildlife is rudimentary. We provide empirical evidence for pathogen co-occurrences by analysing infection matrices for avian malaria (Haemoproteus and Plasmodium spp.) and parasitic filarial nematodes (microfilariae) in wild birds (New Caledonian Zosterops spp.). Using visual and genus-specific molecular parasite screening, we identified high levels of co infections that would have been missed using PCR alone. Avian malaria lineages were assigned to species level using morphological descriptions. We estimated parasite co-occurrence probabilities, while accounting for environmental predictors, in a hierarchical multivariate logistic regression. Co-infections occurred in 36% of infected birds. We identified both positively and negatively correlated parasite co-occurrence probabilities when accounting for host, habitat and island effects. Two of three pairwise avian malaria co-occurrences were strongly negative, despite each malaria parasite occurring across all islands and habitats. Birds with microfilariae had elevated heterophil to lymphocyte ratios and were all co-infected with avian malaria, consistent with evidence that host immune modulation by parasitic nematodes facilitates malaria co-infections. Importantly, co-occurrence patterns with microfilariae varied in direction among avian malaria species; two malaria parasites correlated positively but a third correlated negatively with microfilariae. We show that wildlife co-infections are frequent, possibly affecting infection rates through competition or facilitation. We argue that combining multiple diagnostic screening methods with multivariate logistic regression offers a platform to disentangle impacts of environmental factors and parasite co-occurrences on wildlife disease. PMID- 27561365 TI - Nanocasting Design and Spatially Selective Sulfonation of Polystyrene-Based Polymer Networks as Solid Acid Catalysts. AB - Nanocasting is a general and widely applied method in the generation of porous materials during which a sacrificial solid template is used as a mold on the nanoscale. Ideally, the resulting structure is the inverse of the template. However, replication is not always as direct as anticipated, so the influences of the degree of pore filling and of potential restructuring processes after removal of the template need to be considered. These apparent limitations give rise to opportunities in the synthesis of poly(styrene-co-divinylbenzene) (PSD) polymer networks of widely varying porosities (BET surface area=63-562 m(2) g(-1) ; Vtot =0.18-1.05 cm(3) g(-1) ) by applying a single synthesis methodology. In addition, spatially selective sulfonation on the nanoscale seems possible. Together, nanocasting and sulfonation enable rational catalyst design. The highly porous nanocast and predominantly surface-sulfonated PSD networks approach the activity of the corresponding molecular catalyst, para-toluenesulfonic acid, and exceed those of commercial ion-exchange polymers in the depolymerization of macromolecular inulin. PMID- 27561364 TI - Spontaneous Bacterial Peritonitis due to Actinomyces Mimicking a Perforation of the Proximal Jejunum. AB - BACKGROUND Pelvic-abdominal actinomycosis is a rare chronic condition caused by an anaerobic, gram-negative rod-shaped commensal bacterium of the Actinomyces species. When Actinomyces becomes pathogenic, it frequently causes a chronic infection with granulomatous abscess formation with pus. Due to diversity in clinical and radiological presentation, actinomycosis can easily be mistaken for several other conditions. Peritonitis without preceding abscess formation caused by Actinomyces species has been described in only few cases before in literature. CASE REPORT We report a case of spontaneous pelvic-abdominal peritonitis with presence of pneumoperitoneum and absence of preceding abscesses due to acute actinomycosis mimicking a perforation of the proximal jejunum in a 42-year-old female with an intra-uterine contraceptive device in place. Explorative laparotomy revealed 2 liters of odorless pus but no etiological explanation for the peritonitis. The intra-uterine contraceptive device was removed. Cultivation showed growth of Actinomyces turicensis. The patient was successfully treated with penicillin. CONCLUSIONS In the case of primary bacterial peritonitis or lower abdominal pain without focus in a patient with an intra-uterine device in situ, Actinomyces should be considered as a pathogen. PMID- 27561366 TI - Management of lower urinary tract symptoms associated with benign prostatic hyperplasia in elderly patients with a new diagnostic, therapeutic and care pathway. AB - INTRODUCTION: Benign prostatic hyperplasia (BPH) resulting in lower urinary tract symptoms (LUTS) is a widespread disease that strongly interferes with the quality of life (QoL) of elderly males. It represents a real clinical and socio-economic problem may be due to the lack of a diagnostic, therapeutic and care pathway (DTCP) tool for LUTS/BPH that considers elderly people population in its whole complexity. The aim of this study was to evaluate the clinical effectiveness of the proposed DTCP LUTS/BPH tool. METHODS: This prospective study was conducted on 278 patients over 75 years old with non-neurogenic LUTS recruited from February to July 2014 by 10 general practitioners (GP) and two assisted sanitary residences (ASR). Only five GPs and one ASR were provided with the complete DTCP LUTS/BPH tool to create two different groups of patients: group A (138 patients) was treated without the aid of the DTCP; group B (140 patients) was treated according to the DTCP. RESULTS: At 1 year of follow-up, the patients of Group B compared with Group A achieved a greater and significant mean reduction in the questionnaires score (International Prostate Symptom Score, Quick prostate test and QoL) linked to a higher increase in the flowmetry parameters (Qmax) and a lower postvoid residual. Furthermore, in Group B compared to Group A, a greater improvement of hydronephrosis, creatinine values and erectile dysfunction (ED) were obtained at 1 year of follow-up. CONCLUSION: The encouraging results obtained from this study are significant and support the use of this diagnostic, therapeutic and care tool (DTCP) as the ideal pathway management for elderly men with LUTS associated to BPH and ED. Further studies with greater number of elderly subjects and long-term follow-up are needed to confirm DTCP utility in the clinical management of LUTS/BPH and ED. PMID- 27561367 TI - How are self-rated health and diagnosed disease related to early or deferred retirement? A cross-sectional study of employees aged 55-64. AB - BACKGROUND: More people will probably continue working into old age in the future due to the increased size of aging populations in many countries. We therefore need to know more about older workers' health in relation to their work situation and retirement. This study is a part of a theoretical development of older workers' situations. Older workers' situations are theoretically themed in nine areas by the authors of this study. The aims of the study were to investigate the relationship between: i) diagnosed disease and factors in older workers' situations, theoretically themed in nine areas; ii) self-rated health and factors in older workers' situations, theoretically themed in nine areas; iii) diagnosed disease and self-rated health; and iv) the relationships between these health measures and retirement. METHODS: A questionnaire-based cross-sectional study, using logistic regression, with 1,756 health care personnel aged 55-64 years. The questionnaire used gave an overview of most different areas in the older workers' situations. RESULT: There was a difference in the participants' frequency of objectively specified diagnosed disease and their subjectively experienced self rated health. A bad self-rated health was related higher to early retirement than diagnosed diseases. In the multivariate model, having 'Diagnosed disease' was not significantly related to whether older workers thought they could not work beyond 65 years of age. A bad 'Self-rated health' was also more highly related to whether older workers thought they could not work beyond 65 years, than if the respondents stated that a 'Diagnosed disease is a hindrance in my daily work' in the multivariate model. CONCLUSION: This study showed an important difference between older workers' own experiences and the effect of their self-rated health and their diagnosed diseases. Subjective self-rated health seems to be more important to people's retirement planning than diagnosed disease. The most important factors affecting older workers' self-rated health was the degree to which they felt physically and mentally fatigued, their possibilities for revitalization, and issues of work satisfaction, age discrimination and attitudes of managers to them as seniors. PMID- 27561369 TI - Small bowel obstruction in the virgin abdomen: time to challenge surgical dogma with evidence. AB - BACKGROUND: Although adhesions account for more than 70% of small bowel obstruction (SBO), they are thought to be less likely aetiologies in patients without previous abdominal surgery. Expedient surgery has historically been advocated as prudent management in these patients. Emerging evidence appears to challenge such a dogmatic approach. METHODS: A retrospective analysis was performed in all SBO patients with a virgin abdomen admitted between January 2012 and August 2014. Patients with obstruction secondary to abdominal wall hernias were excluded. Patient demographics, clinical presentation, management strategy and pathology involved were reviewed. RESULTS: A total of 72 patients were included in the study. The majority of patients were males (66.7%), with a median age of 58 years (range: 23-101). Abdominal pain (97%) and vomiting (86%) were the most common presentations while abdominal distention (60%) and constipation (25%) were reported less frequently. Adhesions accounted for the underlying cause in 44 (62%) patients. Other aetiologies included gallstone ileus (n = 5), phytobezoar (n = 5), intussusception (n = 4), internal herniation (n = 4), newly diagnosed small bowel tumour (n = 3), mesenteric volvulus (n = 3), stricture (n = 3) and Meckel's diverticulum (n = 1). Twenty-nine (40%) patients were successfully managed conservatively while the remaining 43 (60%) underwent surgery. The intraoperative findings were in concordance with the preoperative computed tomography scan in 76% of cases. CONCLUSION: Adhesions remain prevalent despite the absence of previous abdominal surgery. Non-operative management is feasible for SBO in a virgin abdomen. Computed tomography scan can be a useful adjunct in discerning patients who may be treated non-operatively by elucidating the underlying cause of obstruction. PMID- 27561370 TI - Optimization of extraction parameters of PTP1beta (protein tyrosine phosphatase 1beta), inhibitory polyphenols, and anthocyanins from Zea mays L. using response surface methodology (RSM). AB - BACKGROUND: Protein tyrosine phosphatase expressed in insulin-sensitive tissues (such as liver, muscle, and adipose tissue) has a key role in the regulation of insulin signaling and pathway activation, making protein tyrosine phosphatase a promising target for the treatment of type 2 diabetes mellitus and obesity and response surface methodology (RSM) is an effective statistical technique for optimizing complex processes using a multi-variant approach. METHODS: In this study, Zea mays L. (Purple corn kernel, PCK) and its constituents were investigated for protein tyrosine phosphatase 1beta (PTP1beta) inhibitory activity including enzyme kinetic study and to improve total yields of anthocyanins and polyphenols, four extraction parameters, including temperature, time, solid-liquid ratio, and solvent volume, were optimized by RSM. RESULTS: Isolation of seven polyphenols and five anthocyanins was achieved by PTP1beta assay. Among them, cyanidin-3-(6"malonylglucoside) and 3'-methoxyhirsutrin showed the highest PTP1beta inhibition with IC50 values of 54.06 and 64.04 MUM, respectively and 4.52 mg gallic acid equivalent/g (GAE/g) of total polyphenol content (TPC) and 43.02 mg cyanidin-3-glucoside equivalent/100 g (C3GE/100g) of total anthocyanin content (TAC) were extracted at 40 degrees C for 8 h with a 33 % solid-liquid ratio and a 1:15 solvent volume. Yields were similar to predictions of 4.58 mg GAE/g of TPC and 42.28 mg C3GE/100 g of TAC. CONCLUSION: These results indicated that PCK and 3'-methoxyhirsutrin and cyanidin-3 (6"malonylglucoside) might be active natural compounds and could be apply by optimizing of extraction process using response surface methodology. PMID- 27561372 TI - Language acquisition is model-based rather than model-free. AB - Christiansen & Chater (C&C) propose that learning language is learning to process language. However, we believe that the general-purpose prediction mechanism they propose is insufficient to account for many phenomena in language acquisition. We argue from theoretical considerations and empirical evidence that many acquisition tasks are model-based, and that different acquisition tasks require different, specialized models. PMID- 27561371 TI - Changes in qualitative and quantitative ultrasound assessment of the gastric antrum before and after elective caesarean section in term pregnant women: a prospective cohort study. AB - Ultrasound measurement of the antral cross-sectional area allows a quantitative estimate of gastric contents in non-pregnant adults, but this relationship may be affected by compression of the stomach exerted by the gravid uterus during pregnancy. This study aimed to assess differences in quantitative (Perlas score) and qualitative (antral cross-sectional area) ultrasound assessments of the gastric antrum performed immediately before and after caesarean section. Forty three women having elective caesarean section performed under spinal anaesthesia were studied in the semirecumbent and semirecumbent-right lateral positions. Thirty-nine women showed no change in stomach contents using the Perlas score between the two measurement periods; four women showed a change, but by one grade only. The median (IQR [range]) antral cross-sectional area was 323 (243-495 [103 908]) mm2 before, and 237 (165-377 [112-762]) mm2 after, caesarean section in the semirecumbent position (p = 0.001); the comparable values in the semirecumbent right lateral position were 418 (310-640 [161-1238]) mm2 and 362 (280-491 [137 1231]) mm2 (p = 0.09). The distance between the skin and the antrum, and the aorta and the antrum, decreased significantly in both positions after surgery. We suggest that our results indicate that stomach contents remain largely unchanged in women having elective caesarean section, but antral cross-sectional area decreases, especially in the semirecumbent position, related to a change in the position of the stomach within the abdomen. This implies that the relationship of antral cross-sectional area to volume of stomach contents, which has been determined for non-pregnant subjects, may not apply in term pregnant women. PMID- 27561374 TI - Reservoir computing and the Sooner-is-Better bottleneck. AB - Prior language input is not lost but integrated with the current input. This principle is demonstrated by "reservoir computing": Untrained recurrent neural networks project input sequences onto a random point in high-dimensional state space. Earlier inputs can be retrieved from this projection, albeit less reliably so as more input is received. The bottleneck is therefore not "Now-or-Never" but "Sooner-is-Better." PMID- 27561373 TI - Posttraumatic levels of liver enzymes can reduce the need for CT in children: a retrospective cohort study. AB - BACKGROUND: Computed tomography (CT) is the gold standard in the initial evaluation of the hemodynamically stable patient with suspected liver trauma. However, the adverse effects of radiation exposure are of specific concern in the pediatric population. It is therefore desirable to explore alternative diagnostic modalities. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic enzymes, which are elevated in peripheral blood in relation to liver injury. The aim of the present study was to investigate a potential role of normal liver transaminase levels in the decision algorithm in suspected pediatric blunt liver trauma. METHODS: Retrospective analysis of consecutively collected data from children (0-17 years) with blunt liver trauma, admitted to a single trauma centre in Denmark, between 2000 and 2013. Patients underwent abdominal CT during initial evaluation, and initial AST and/or ALT was measured. Based on local guidelines, we set the threshold for blood AST and ALT level to 50 IU/L. Nonparametric statistical tests were used. RESULTS: Sixty consecutive children with liver injury following blunt abdominal trauma were enrolled in the study. All patients with normal AST and/or ALT level were treated conservatively with success. Information on both AST and ALT was available in 47 children. Of these 47 children, three children had AST and ALT levels <=50 IU/L. These children suffered from grade I liver injuries, and were treated conservatively with no complications. DISCUSSION: All children who presented with blunt liver injury and AST and ALT levels <=50 IU/L did not require treatment. These findings indicate that AST and ALT could be included in an updated management algorithm as a screening method to avoid abdominal CT. Notable limitations to the study was the retrospective method of data collection, without inclusion of a control group. CONCLUSIONS: CT seems superfluous in the initial evaluation of hemodynamically stable children with suspected blunt liver injury and blood AST and ALT levels <=50 IU/L. PMID- 27561375 TI - Review article: Why is there still a debate regarding the safety and efficacy of intravenous thrombolysis in the management of presumed acute ischaemic stroke? A systematic review and meta-analysis. AB - OBJECTIVE: The objective of the present study is to independently and systematically assess the harms and benefits of intravenous thrombolysis for patients with presumed acute schaemic stroke. METHODS: We performed a systematic review and meta-analysis of randomised clinical trials of intravenous thrombolysis compared with control in patients with presumed acute ischaemic stroke. The effectiveness of thrombolysis on functional outcome, symptomatic intracranial haemorrhage, early mortality and mortality at final follow up was assessed using a fixed-effect meta-analysis. RESULTS: A total of 26 studies that randomised 10 431 participants were included. The use of thrombolysis was associated with an increased odds of good functional outcome, estimated odds ratio (OR) 1.14 (95% confidence interval [CI] 1.04-1.25, P = 0.004), and also a significantly increased risk of symptomatic intracranial haemorrhage, estimated OR 4.28 (95% CI 3.34-5.48, P < 0.0005) and an increased risk of early mortality, estimated OR 1.51 (95% CI 1.27-1.78, P < 0.0005). There was no statistically significant evidence that the effect of recombinant tissue plasminogen activator (rt-PA) was different from that of other thrombolytic agents. There was also an increase in mortality at final follow up associated with treatment with thrombolysis, estimated OR 1.17 (95% CI 1.06-1.30, P = 0.003), although this result was not consistent when limited to studies of rt-PA, estimated OR 1.04 (95% CI 0.92-1.18, P = 0.49). CONCLUSIONS: There is clear evidence of increased early mortality, increased rates of symptomatic intracranial haemorrhage and also of improved functional outcomes for patients with presumed acute ischaemic stroke treated with thrombolysis. The available data are unlikely to resolve the controversy regarding the use of intravenous thrombolysis in this population, and further randomised controlled trials are urgently required. PMID- 27561376 TI - Rivastigmine patch reduces the incidence of postoperative delirium in older patients with cognitive impairment. AB - OBJECTIVE: To date, data regarding the efficacy of acetylcholinesterase inhibitors in preventing postoperative delirium (POD) are inconsistent and conflicting. Older individuals with cognitive dysfunction are thought to show POD more frequently. Our aim was to study the effectiveness of rivastigmine prophylaxis on the incidence, severity, and risk factors for POD in older patients with cognitive impairment undergoing hip fracture surgery. METHODS: Of 62 older patients with cognitive impairment about to undergo surgery after a hip fracture, 31 were randomly assigned to receive a rivastigmine patch from 3 days before to 7 days after the operation (Group I), and the other 31 did not receive a rivastigmine patch (Group II). The two groups were compared with regard to incidence and severity of delirium on postoperative days 2 or 3 and 7. Multivariate logistic regression analysis was performed to assess factors associated with POD. RESULTS: Postoperative delirium occurred in five Group I patients and 14 Group II patients (p = 0.013). The mean severity of delirium in the two groups as determined by the Delirium Rating Scale was 2.2 and 6.2 respectively (p = 0.033). The odds ratio for POD was 0.259 (95% CI: 0.074-0.905, p = 0.034) after adjusting for American Society of Anesthesiologists score (p = 0.058), age (p = 0.203), and gender (p = 0.560). There were no rivastigmine related perioperative complications. CONCLUSION: Perioperative rivastigmine patch application could reduce the occurrence of POD in older patients with low cognitive status. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27561378 TI - Psychiatric hospitalisation among individuals with intellectual disability referred to the START crisis intervention and prevention program. AB - BACKGROUND: Little is known about inpatient psychiatric hospitalisation among adults with intellectual disability (ID) in the United States. Greater research is, therefore, required to inform efforts aimed at preventing this costly and restrictive form of care. METHODS: Data were from 3299 individuals with ID (mean age = 31 years; SD = 14 years) who were referred to START (Systemic, Therapeutic, Assessment, Resources, and Treatment), a community-based crisis intervention and prevention programme. A random effects logistic regression model was used to examine the association between 11 factors and caregiver report of psychiatric hospitalisation in the past 12 months. RESULTS: Twenty eight percent of the sample had at least one psychiatric inpatient stay in the prior year. Factors associated with an increased likelihood of prior hospitalisation included: younger age, diagnosis of a psychotic disorder, a score of >30 on the irritability subscale of the Aberrant Behavior Checklist, increasing number of psychiatric diagnoses, less severe ID, Black/AA race and not having a home and community waiver. CONCLUSIONS: Among this high-risk referred group, more than 1 in 4 individuals were hospitalised in the year prior to referral. While results from the analyses will help profile those at risk for hospitalisation, the findings suggest that interventions at the policy level may play an important role in reducing psychiatric hospitalisation. PMID- 27561377 TI - Signaling cascades transmit information downstream and upstream but unlikely simultaneously. AB - BACKGROUND: Signal transduction is the process through which cells communicate with the external environment, interpret stimuli and respond to them. This mechanism is controlled by signaling cascades, which play the role of intracellular transmitter, being able to transmit biochemical information between cell membrane and nucleus. In theory as well as in practice, it has been shown that a perturbation can propagate upstream (and not only downstream) a cascade, by a mechanism known as retroactivity. This study aims to compare the conditions on biochemical parameters which favor one or the other direction of signaling in such a cascade. RESULTS: From a mathematical point of view, we show that the steady states of a cascade of arbitrary length n are described by an iterative map of second order, meaning that the cascade tiers are actually coupled three-by three. We study the influence of the biochemical parameters in the control of the direction of transmission - upstream and/or downstream - along a signaling cascade. A numerical and statistical approach, based on the random scan of parameters describing a 3-tier signaling cascade, provides complementary findings to the analytical study. In particular, computing the likelihood of parameters with respect to various signaling regimes, we identify conditions on biochemical parameters which enhance a specific direction of propagation corresponding to forward or retro-signaling regimes. A compact graphical representation is designed to relay the gist of these conditions. CONCLUSIONS: The values of biochemical parameters such as kinetic rates, Michaelis-Menten constants, total concentrations of kinases and of phosphatases, determine the propensity of a cascade to favor or impede downstream or upstream signal transmission. We found that generally there is an opposition between parameter sets favoring forward and retro-signaling regimes. Therefore, on one hand our study supports the idea that in most cases, retroactive effects can be neglected when a cascade which is efficient in forward signaling, is perturbed by an external ligand inhibiting the activation at some tier of the cascade. This result is relevant for therapeutic methodologies based on kinase inhibition. On the other hand, our study highlights a less-known part of the parameter space where, although the forward signaling is inefficient, the cascade can interestingly act as a retro-signaling device. PMID- 27561379 TI - Reply to reviewers: Reuse, embodied interactivity, and the emerging paradigm shift in the human neurosciences. AB - In this reply to reviewers, I argue that, although reforming the taxonomy of psychology will lead to great insights in the cognitive sciences, it will not result in 1:1 structure-function mappings in the brain; we should expect to see a great deal of irreducible functional diversity in the brain at multiple spatial scales. I further clarify both the promise and the limitations of the analytic techniques for capturing functional diversity and interrogating the taxonomy of psychology; describe the ways in which neural reuse can help us understand human development; further explore the ways in which my proposals for integrating psychology, neuroscience, and evolutionary biology differ from the approach exemplified by contemporary evolutionary psychology; and lay out some new and hopefully interesting avenues for future research. PMID- 27561380 TI - Decorating CoP and Pt Nanoparticles on Graphitic Carbon Nitride Nanosheets to Promote Overall Water Splitting by Conjugated Polymers. AB - The splitting of water into H2 and O2 using solar energy is one of the key steps in artificial photosynthesis for the future production of renewable energy. Here, we show the first use of CoP and Pt nanoparticles as dual co-catalysts to modify graphitic carbon nitride (g-C3 N4 ) polymer to achieve overall water splitting under visible light irradiation. Our findings demonstrate that loading dual co catalysts on delaminated g-C3 N4 imparts surface redox sites on the g-C3 N4 nanosheets that can not only promote catalytic kinetics but also promote charge separation and migration in the soft interface, thus improving the photocatalytic efficiency for overall water splitting. This robust, abundant, and stable photocatalyst based on covalent organic frameworks is demonstrated to hold great promise by forming heterojunctions with CoP and Pt for catalyzing the direct splitting of water into stoichiometric H2 and O2 using energy from photons. PMID- 27561381 TI - Multi-level selection, social signaling, and the evolution of human suffering gestures: The example of pain behaviors. AB - Pain suffering has been naturally selected to be experienced and expressed within a wider social system. The communication of pain improves group coordination and decision-making about engaging in resource dependent and potentially risky endeavors. Recent findings warrant the development of a cohesive framework for understanding the reciprocal nature of pain expression and individual and group level outcomes that can generate novel predictions on the heuristical expression of human suffering in naturalistic and clinical settings. PMID- 27561383 TI - How evolved psychological mechanisms empower cultural group selection. AB - Driven by intergroup competition, social norms, beliefs, and practices can evolve in ways that more effectively tap into a wide variety of evolved psychological mechanisms to foster group-beneficial behavior. The more powerful such evolved mechanisms are, the more effectively culture can potentially harness and manipulate them to generate greater phenotypic variation across groups, thereby fueling cultural group selection. PMID- 27561382 TI - Dihydrotestosterone synthesis pathways from inactive androgen 5alpha-androstane 3beta,17beta-diol in prostate cancer cells: Inhibition of intratumoural 3beta hydroxysteroid dehydrogenase activities by abiraterone. AB - Intratumoural dihydrotestosterone (DHT) synthesis could be an explanation for castration resistance in prostate cancer (PC). By using liquid chromatography mass spectrometry, we evaluated the intratumoral DHT synthesis from 5alpha androstane-3beta,17beta-diol (3beta-diol), which is inactive androgen metabolized from DHT. 3beta-diol had biochemical potential to be converted to DHT via three metabolic pathways and could stimulate PC cell growth. Especially, 3beta-diol was not only converted back to upstream androgens such as dehydroepiandrosterone (DHEA) or Delta5-androstenediol but also converted directly to DHT which is the main pathway from 3beta-diol to DHT. Abiraterone had a significant influence on the metabolism of DHEA, epiandrosterone and 3beta-diol, by the inhibition of the intratumoural 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activities which is one of key catalysts in androgen metabolic pathway. The direct-conversion of 3beta-diol to DHT was catalysed by 3beta-HSD and abiraterone could inhibit this activity of 3beta-HSD. These results suggest that PC had a mechanism of intratumoural androgen metabolism to return inactive androgen to active androgen and intratumoural DHT synthesis from 3beta-diol is important as one of the mechanisms of castration resistance in PC. Additionally, the inhibition of intratumoural 3beta-HSD activity could be a new approach to castration-resistant prostate cancer treatment. PMID- 27561384 TI - Agriculture increases individual fitness. AB - We question the need to explain the onset of agriculture by appealing to the second type of multilevel selection (MLS2). Unlike eusocial insect colonies, human societies do not exhibit key features of evolutionary individuals. If we avoid the mistake of equating Darwinian fitness with health and quality of life, the adoption of agriculture is almost certainly explicable in terms of individual level selection and individual rationality. PMID- 27561385 TI - Giant cell-rich osteosarcoma of the parotid gland: An exceptionally rare entity at an unusual site. AB - Giant cell-rich osteosarcoma is a rare histologic variant of conventional osteosarcoma that affects mainly the extremities. Extraskeletal giant cell-rich osteosarcoma is therefore exceedingly rare. Here, we report the first case of this uncommon tumor involving the parotid gland in a 62-year-old male who presented with initial right jaw swelling. Radiologic work-up revealed a 6.2 cm mass involving the right parotid gland. Fine-needle aspiration cytology showed numerous multinucleated giant cells in a background of dyshesive epithelioid cells and rare clusters of spindle stromal cells, suspicious for malignancy. The subsequent excisional biopsy showed histopathologic features diagnostic for giant cell-rich osteosarcoma. Diagn. Cytopathol. 2016;44:1107-1111. (c) 2016 Wiley Periodicals, Inc. PMID- 27561386 TI - BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality. AB - A delay in liver regeneration after partial hepatectomy (PHx) leads to acute liver injury, and such delays are frequently observed in aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, and BubR1 down-regulation promotes aging-associated phenotypes. In this study we investigated the effects of BubR1 insufficiency on liver regeneration in mice. Low-BubR1-expressing mutant (BubR1(L/L)) mice had a delayed recovery of the liver weight-to-body weight ratio and increased liver deviation enzyme levels after PHx. Microscopic observation of BubR1(L/L) mouse liver showed an increased number of necrotic hepatocytes and intercalated disc anomalies, resulting in widened inter-hepatocyte and perisinusoidal spaces, smaller hepatocytes and early-stage microvilli atrophy. Up regulation of desmocollin-1 (DSC1) was observed in wild-type, but not BubR1(L/L), mice after PHx. In addition, knockdown of BubR1 expression caused down-regulation of DSC1 in a human keratinocyte cell line. BubR1 insufficiency results in the impaired liver regeneration through weakened microstructural adaptation against PHx, enhanced transient liver failure and delayed hepatocyte proliferation. Thus, our data suggest that a reduction in BubR1 levels causes failure of liver regeneration through the DSC1 abnormality. PMID- 27561387 TI - Effects of polyphenol-rich plant products from grape or hop as feed supplements on the expression of inflammatory, antioxidative, cytoprotective and endoplasmic reticulum stress-related genes and the antioxidative status in the liver of piglets. AB - Recent studies have shown that supplementation of plant products rich in polyphenols exerts anti-inflammatory effects in the small intestine and improves feed conversion in piglets. This study aimed to investigate whether dietary polyphenols have also anti-inflammatory and cytoprotective effects in the liver of piglets. For this end, relative mRNA concentrations of eight genes involved in proinflammatory pathways, eight genes involved in the antioxidative and cytoprotective system, six genes of phase I and phase II metabolism and 15 genes of the unfolded protein response (triggered by stress of the endoplasmic reticulum) in the liver of pigs fed diets supplemented with either 1% of grape seed and grape marc meal extract (GME) or 1% spent hops (SH) as sources of polyphenols were determined. Relative mRNA concentrations of almost all these genes, with few exceptions, in the liver of pigs supplemented with GME or SH did not differ from those in the liver of control piglets. Gene expression data were validated by consideration of concentrations of some selected proteins of these pathways which also did not differ between piglets supplemented with GME or SH and control piglets. Moreover, concentrations of thiobarbituric acid-reactive substances and tocopherols as well as the total antioxidant capacity in liver and plasma did not differ between pigs supplemented with either GME or SH and control piglets. Overall, this study shows that supplementation of GME or SH as sources of polyphenols does not influence hepatic pathways linked to inflammation, the antioxidant and cytoprotective system, stress of the endoplasmic reticulum and the xenobiotic system in healthy piglets. PMID- 27561389 TI - Resistance to cancer chemotherapy as an atavism? (retrospective on DOI 10.1002/bies.201300170). PMID- 27561388 TI - The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta. AB - Since the first observation of a helical flow pattern in aortic blood flow, the existence of helical blood flow has been found to be associated with various pathological conditions such as bicuspid aortic valve, aortic stenosis, and aortic dilatation. However, an understanding of the development of helical blood flow and its clinical implications are still lacking. In our present study, we hypothesized that the direction and angle of aortic inflow can influence helical flow patterns and related hemodynamic features in the thoracic aorta. Therefore, we investigated the hemodynamic features in the thoracic aorta and various aortic inflow angles using patient-specific vascular phantoms that were generated using a 3D printer and time-resolved, 3D, phase-contrast magnetic resonance imaging (PC MRI). The results show that the rotational direction and strength of helical blood flow in the thoracic aorta largely vary according to the inflow direction of the aorta, and a higher helical velocity results in higher wall shear stress distributions. In addition, right-handed rotational flow conditions with higher rotational velocities imply a larger total kinetic energy than left-handed rotational flow conditions with lower rotational velocities. PMID- 27561391 TI - Disengaging from the ultrasocial economy: The challenge of directing evolutionary change. AB - We appreciate the depth and breadth of comments we received. They reflect the interdisciplinary challenge of our inquiry and reassured us of its broad interest. We believe that our target article and the criticisms, elaborations, and extensions of the commentators can be an important contribution to establishing human ultrasociality as a new field of social science inquiry. A few of the commentators questioned our definition of ultrasociality, and we begin our response with an elaboration of that definition and a defense of our argument that human ultrasociality began with agriculture. We then respond to the second major area of controversy, namely, our use of group selection to explain the economic drivers behind the agricultural transition. We then focus on the issue of human intentionality raised by the phenomenon of collective intelligence. The intriguing question is to what extent can an entire culture change its own destiny? We then address the issue of the division of labor raised by a number of commentators. The complex division of labor was both a driver and a defining characteristic of ultrasociality, even though it was present in simpler forms in earlier societies. The remaining issues addressed include energy and complexity, expansion and sustainability, and the accelerating evolution of human ultrasociality. These were raised by only a few commentators, but their importance warrants further elaboration. PMID- 27561390 TI - The tumour suppressor CYLD regulates the p53 DNA damage response. AB - The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF kappaB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. Ubiquitin chain-restriction analysis provides evidence that CYLD removes K48 ubiquitin chains from p53 indirectly by cleaving K63 linkages, suggesting that p53 is decorated with complex K48/K63 chains. Moreover, CYLD deficiency also diminishes CEP-1/p53-dependent DNA damage-induced germ cell apoptosis in the nematode Caenorhabditis elegans. Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD. PMID- 27561393 TI - Bachelor of public health course to upgrade the competencies of health assistants. PMID- 27561392 TI - Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis. AB - The protozoan parasite Trypanosoma brucei causes the fatal illness human African trypanosomiasis (HAT). Standard of care medications currently used to treat HAT have severe limitations, and there is a need to find new chemical entities that are active against infections of T. brucei. Following a "drug repurposing" approach, we tested anti-trypanosomal effects of carbazole-derived compounds called "Curaxins". In vitro screening of 26 compounds revealed 22 with nanomolar potency against axenically cultured bloodstream trypanosomes. In a murine model of HAT, oral administration of compound 1 cured the disease. These studies established 1 as a lead for development of drugs against HAT. Pharmacological time-course studies revealed the primary effect of 1 to be concurrent inhibition of mitosis coupled with aberrant licensing of S-phase entry. Consequently, polyploid trypanosomes containing 8C equivalent of DNA per nucleus and three or four kinetoplasts were produced. These effects of 1 on the trypanosome are reminiscent of "mitotic slippage" or endoreplication observed in some other eukaryotes. PMID- 27561394 TI - Challenges in new vaccine introduction in a national program in India. AB - Vaccines have a long history dating back to the days of Edward Jenner (1749-1823) and Louis Pasteur (1822-1895). Vaccines can be viewed from a public health perspective as well as scientific perspective. Public health experts would focus epidemiological relevance, immunological competency, and technological feasibility. Scientists however will look for a good immune response as well as long-lived immunity, stability considerations, and safety issues such as danger of reversion to virulence. In India, the vaccine coverage is far from satisfactory, national average for full immunization being only 65%. Presently, nine vaccines are being used in the Universal Immunization Program. However, some more have started in pilot, and some are still in the pipeline. Although administrative, logistic and operational challenges have to be faced when introducing a new vaccine into the public health system; these are solvable and should not be a hindrance to the introduction. A real-life example of nonintroduction of a lifesaving vaccine is - the oral cholera vaccine. This vaccine which is manufactured and licensed in India has been the World Health Organization (WHO) prequalified, and it is being used worldwide. Although the disease is a major threat, the disease has its stigma and has led to its low reporting even from cholera endemic areas of the country. Thus, in spite of the WHO recommendations, the vaccine is not being introduced into the national program which would take it to people who need it the most only because of apparent lack of sufficient disease burden data and political commitment. PMID- 27561395 TI - Low-quality scientific evidence for the continuation of universal Vitamin A supplementation among under 5 children in India. AB - Vitamin A supplementation (VAS) is presently being undertaken in India among under 5 (U5) children for two possible benefits (i) to prevent nutritional blindness due to Vitamin A deficiency (VAD) and (ii) to reduce U5 mortality. The existing scientific evidence suggests that nutritional blindness due to VAD has been virtually eliminated and also the difference between U5 mortality rate and infant mortality rate is very low for VAS to have any meaningful impact. On the contrary, scientific evidence indicates that there could be side effects of the administration of mega dose of Vitamin A (MDVA). These side effects of MDVA have not been systematically investigated. The universal VAS should be discontinued immediately as there are no likely benefits to U5 children. PMID- 27561396 TI - Taking stocks of antimalarial activities: A study on knowledge and skill of health personnel at primary care setting in the state of West Bengal, India. AB - BACKGROUND: Early diagnosis and effective treatment are the key areas in malaria control in India. OBJECTIVE: The present study was carried out to assess the knowledge and skill of health personnel at primary care level and the logistic support related to the program at subcenter (SC) level. METHODS: A cross sectional, descriptive study was conducted among medical and paramedical personnel working at primary health-care institutions in two districts of West Bengal. Knowledge was assessed using a structured questionnaire while diagnostic skill and logistic support were assessed with structured checklists. Clinical skill was assessed with case vignettes. RESULTS: Requisite knowledge on diagnostic procedure was found in two-third to three-fourth of health personnel while only 26.7% and 12.4%, respectively, knew the correct treatment of Plasmodium vivax and Plasmodium falciparum malaria. Median standardized score for knowledge was 50.0 while the scores for skill of preparing blood slide and for rapid diagnostic test were 70.0 and 57.1, respectively. Education and work experience were related to diagnostic skill but had little effect on knowledge. In clinical skill, medical personnel scored 50% or more in investigation and treatment aspects only. In another case vignette, health workers excelled over medical officers and other staff in all axes other than history taking and clinical examination although their performance was also suboptimal. Formal training on malaria did not show any bearing on median knowledge and skill score. Supply of diagnostics and drugs was insufficient in majority of SCs. CONCLUSION: Renewed efforts are needed to create competent workforce and ensure adequate logistic supply. PMID- 27561397 TI - Assessment and comparison of pregnancy outcome among anaemic and non anaemic primigravida mothers. AB - BACKGROUND: Primigravidas (PGs) are high-risk women and anemia in pregnancy is one of the commonest causes of maternal morbidity and mortality. OBJECTIVES: The study was conducted to assess impact of anemia on course and outcome of pregnancy in anemic (Hemoglobin 8-10.9 gm%) and nonanemic PGs. METHODS: This prospective longitudinal study was conducted in All India Institute of Medical Sciences, New Delhi. PGs 20-30 years age, gestation age 16-18 weeks, hemoglobin >8 gm%, live singleton pregnancy, and no other medical illness were recruited after informed consent. The women were Grouped 1 and 2 if hemoglobin was >=11 gm% and 8-10.9 gm%, respectively. Complete hemogram done at enrollment, 28-30 weeks of pregnancy and 6 weeks postdelivery. Obstetric outcome and presence of anemia postdelivery were compared between groups using Chi-square test and Fisher's exact test. RESULTS: A total of 377 PGs were enrolled and obstetric outcomes studied in 179 (Group 1) and 149 (Group 2) excluding women who did not complete study. There was no statistically significant difference in baseline characteristics, antenatal complications, gestational age, mode of delivery, and neonatal outcome. At 28-30 weeks of gestation, in spite of iron supplementation higher percentage (64.4%) (P < 0.05) of anemic patients remained anemic. At 6 weeks postdelivery, 15.6% and 24.2% were anemic in Group 1 and 2, respectively (P > 0.05). The adverse postpartum events (7.6%) were seen more in anemic compared to nonanemic pregnant women (P < 0.05). CONCLUSIONS: Cautious approach required in postpartum period of anemic women though antenatal period is similar as nonanemic pregnant women. PMID- 27561398 TI - Comparison of satisfaction with maternal health-care services using different health insurance schemes in aceh province, Indonesia. AB - BACKGROUND: An insurance scheme called Jaminan Kesehatan Aceh (JKA) was established by the local government to achieve universal coverage for Aceh's population who were not registered under the national insurance scheme for the poor (Jamkesmas). OBJECTIVE: This study was conducted to compare women's satisfaction before and after the implementation of JKA and across different insurance schemes. METHODS: The study was conducted from July 2011 to July 2012 on satisfaction of maternal health services among 1197, 15-49 years aged old women living in eight districts of Aceh Province, Indonesia, and a cluster sampling technique was applied. Analysis of variance was used to assess the effects of different insurance schemes, period, and type of services on satisfaction with maternal health services. RESULTS: Women were mostly satisfied with birth delivery services (mean score: 2.69) followed by postnatal care (mean score: 2.62) and antenatal care services (mean score: 2.37). CONCLUSION: Over the changing period, the average level of satisfaction in the JKA group increased significantly. PMID- 27561399 TI - A comparative study of skeletal fluorosis among adults in two study areas of Bangarpet taluk, Kolar. AB - BACKGROUND: Skeletal fluorosis is a crippling disease resulting from excessive exposure to high fluoride from different sources. OBJECTIVES: To assess the prevalence of skeletal fluorosis in Bangarpet taluk of Kolar, to compare various epidemiological factors influencing the occurrence of skeletal fluorosis among the two groups with differential water fluoride levels, and to estimate fluoride levels in all the sources of drinking water in study areas. METHODS: A cross sectional study was conducted among the adults of three randomly selected villages of Bangarpet taluk, Thimmasandra, Batavarahalli, with high (>1.5 mg/L) and Maddinayakanahalli with normal (<1.0 mg/L) fluoride levels. A house-to-house survey was conducted by administering a semi-structured questionnaire. Skeletal fluorosis was assessed by three simple physical tests in the field followed by radiological confirmation among the positives. Fluoride levels of drinking water sources were estimated by the ion-electrode method. Chi-square and Fisher's exact tests were used as tests of association. RESULTS: The prevalence of skeletal fluorosis at field level in both high and normal fluoride groups was 5.0%. Water fluoride levels in Thimmasandra, Batavarahalli, and Maddinayakanahalli were 4.13 mg/L, 2.59 mg/L, and 0.61 mg/L, respectively. Among the subjects with skeletal fluorosis, a significant difference was observed between socioeconomic status and prevalence of skeletal fluorosis in both high and normal fluoride groups (P < 0.05). CONCLUSION: Skeletal fluorosis is a threat among elderly in Bangarpet taluk, Kolar district. PMID- 27561400 TI - Quality of life and sociodemographic factors associated with poor quality of life in elderly women in Thiruvananthapuram, Kerala. AB - BACKGROUND: India is going through a phase of demographic transition leading to population aging and feminization of aging resulting in increased proportion of elderly women than men. Problems faced by the elderly women are more critical than men due to family and social conditions prevailing in India. OBJECTIVE: The study made an attempt to assess the quality of life (QOL) using the World Health Organization QOL (WHOQOL-BREF) scale and sociodemographic factors affecting QOL of elderly women residing in a community setting in South Kerala. METHODS: A community-based, cross-sectional study to assess the QOL of elderly women using WHOQOL-BREF questionnaire. Data were collected from 160 elderly women. RESULTS: 2.5% (95% confidence interval [CI]: 0.07-4.84) of the study participants were having "very good" QOL. 38.8% (95% CI: 31.2-46.4) had "good," 43.1% (95% CI: 35.4 50.8) had "poor," and 15.6% (95% CI: 9.98-21.22) had "very poor" QOL, respectively. QOL was least in the psychological domain followed by physical and health-related, social, and environmental domains. Logistic regression revealed age above 70 years (adjusted odds ratio [OR] - 11.3), nonpossession of property (adjusted OR - 8.99), neglecting attitude by family (adjusted OR - 6.9), and absence of visit by friends and relatives (adjusted OR - 9.9) as risk factors, whereas residing in the urban area as a protective factor (adjusted OR - 0.1) for poor QOL. CONCLUSION: It is possible to improve the QOL of elderly women by providing financial security, ensuring care, and by enhancing social relationships of elderly women. PMID- 27561401 TI - Personal vis-a-vis social responsibility for disparities in health status: An issue of justice. AB - Health inequities are disparities which can be avoided through rational actions on the part of policymakers. Such inequalities are unnecessary and unjust and may exist between and within nations, societies, and population groups. Social determinants such as wealth, income, occupation, education, gender, and racial/ethnic groups are the principal drivers of this inequality since they determine the health risks and preventive behaviors, access to, and affordability of health care. Within this framework, there is a debate on assigning a personal responsibility factor over and above societal responsibility to issues of ill health. One school of philosophy argues that when individuals are worse-off than others for no fault of their own, it is unjust, as opposed to health disparities that arise due to avoidable personal choices such as smoking and drug addiction for which there should (can) be a personal responsibility. Opposing thoughts have pointed out that the relative socioeconomic position of an individual dictates how his/her life may progress from education to working conditions and aging, susceptibility to diseases and infirmity, and the consequences thereof. The existence of a social gradient in health outcomes across populations throughout the world is a testimony to this truth. It has been emphasized that assuming personal responsibility for health in public policy-making can only have a peripheral place. Instead, the concept of individual responsibility should be promoted as a positive concept of enabling people to gain control over the determinants of health through conscious, informed, and healthy choices. PMID- 27561402 TI - Public Health Research and Scheduled Tribes: An ethical lens. AB - In this commentary, it is argued that greater attention paid to ethical considerations related to doing Public Health Research with Scheduled Tribes (STs) should be prioritized. Given the high levels of health needs among STs as well as their high levels of deprivation, cultural oppression, and impingement on their rights, there is a need to revisit our research practices to contribute to better health and overall empowerment. Specific strategies that could be integrated into research practice are offered. The paper concludes with a call for the development of national guidelines for Public Health Research with STs. PMID- 27561404 TI - Annual report of the association for the year 2015. PMID- 27561403 TI - Evaluation of governmental oral health-care infrastructure in the state of Haryana. AB - Health system should be organized to meet the needs of entire population of the nation. Oral diseases are the most common of the chronic diseases, but there are few efficient dental care systems to cope with these problems. The present cross sectional study was conducted among 135 dental care units of various primary health centers, community health centers, and general hospitals existing in the state to evaluate the government oral health-care infrastructure in Haryana. Data regarding provision of water and electricity supply, dental workforce and their qualification, number and type of instruments in the dental operatory unit, etc., were collected on a structured format. There is a shortfall in infrastructure and significant problem with the adequacy of working facilities. This can prove to be a big hurdle in the provision of adequate oral health care to people with greatest health-care needs. A great deal of effort is required to harmonize the oral health-care delivery system. PMID- 27561405 TI - Auditor's Report. PMID- 27561406 TI - Students' perception of quality of medical education in a medical college in West Bengal, India. PMID- 27561407 TI - Students' perception of quality of medical education in a medical college in West Bengal, India. PMID- 27561408 TI - A novel SoxB2 gene is required for maturation of sperm nucleus during spermiogenesis in the Chinese mitten crab, Eriocheir sinensis. AB - SRY-related HMG box (Sox) genes are characterized by the presence of a DNA binding HMG domain and involved in a diverse range of developmental processes. In this study, we identified a novel Sox gene, designated as EsSoxB2-1, from the Chinese mitten crab Eriocheir sinensis. The EsSoxB2-1 encodes a protein of 259 amino acids, sharing the highest identity with the beetle Tribolium castaneum SOX21b. Unlike insect Sox21b, however, EsSoxB2-1 is intronless and exhibits a gonad-specific expression pattern at both mRNA and protein level. Two core promoters in 5' flanking region were demonstrated to be essential for inducing transcriptional regulatory activity. The transcription of EsSoxB2-1 mRNA begins in spermatogonia stage, while the translation of EsSOXB2-1 protein initiates at spermiogenesis stage. Interestingly, EsSOXB2-1 protein was exclusively localized in the nucleus of spermatid and spermatozoa even at the end of acrosome reaction, and was bound to the uncondensed chromatin in nucleoplasm of mature spermatozoa. Knockdown of EsSoxB2-1 by RNAi leads to abnormal transformation of the nucleus during spermiogenesis. Together, these findings demonstrated the requirement of EsSoxB2-1 for the spermatozoa nucleus maturation and also suggested that EsSoxB2 1 would be delivered into fertilized eggs along with chromatins as a paternal transcription factor for regulating early embryonic development. PMID- 27561409 TI - RNA-sequencing profiles hippocampal gene expression in a validated model of cancer-induced depression. AB - To investigate the pathophysiology of cancer-induced depression (CID), we have recently developed a validated CID mouse model. Given that the efficacy of antidepressants in cancer patients is controversial, it remains unclear whether CID is a biologically distinct form of depression. We used RNA-sequencing (RNA seq) to investigate differentially expressed genes (DEGs) in hippocampi of animals from our CID model relative a positive control model of depressive-like behavior induced with chronic corticosterone (CORT). To validate RNA-seq results, we performed quantitative real-time RT-PCR (qRT-PCR) on a subset of DEGs. Enrichment analysis using DAVID was performed on DEGs to identify enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and biological process gene ontologies (GO:BP). qRT-PCR results significantly predicted RNA-seq results. RNA seq revealed that most DEGs identified in the CORT model overlapped with the CID model. Enrichment analyses identified KEGG pathways and GO:BP terms associated with ion homeostasis and neuronal communication for both the CORT and CID model. In addition, CID DEGs were enriched in pathways and terms relating to neuronal development, intracellular signaling, learning and memory. This study is the first to investigate CID at the mRNA level. We have shown that most hippocampal mRNA changes that are associated with a depressive-like state are also associated with cancer. Several other changes occur at the mRNA level in cancer, suggesting that the CID model may represent a biologically distinct form of a depressive like state. PMID- 27561410 TI - Ecological constraints increase the climatic debt in forests. AB - Biodiversity changes are lagging behind current climate warming. The underlying determinants of this climatic debt are unknown and yet critical to understand the impacts of climate change on the present biota and improve forecasts of biodiversity changes. Here we assess determinants of climatic debt accumulated in French forest herbaceous plant communities between 1987 and 2008 (that is, a 1.05 degrees C mean difference between the observed and bioindicated temperatures). We show that warmer baseline conditions predispose plant communities to larger climatic debts, and that climate warming exacerbates this response. Forest plant communities, however, are absorbing part of the temperature increase mainly through the species' ability to tolerate changing climate. As climate warming is expected to accelerate during the twenty-first century, plant migration and tolerance to climatic stresses probably will be insufficient to absorb this impact posing threats to the sustainability of forest plant communities. PMID- 27561411 TI - Dramatic mass loss in extreme high-elevation areas of a western Himalayan glacier: observations and modeling. AB - Rapid climate change at high elevations has accelerated glacier retreat in the Himalayas and Tibetan Plateau. However, due to the lack of long-term glaciological measurements, there are still uncertainties regarding when the mass loss began and what the magnitude of mass loss is at such high elevations. Based on in situ glaciological observations during the past 9 years and a temperature index mass balance model, this study investigates recent mass loss of the Naimona'nyi Glacier in the western Himalayas and reconstructs a 41-year (1973/74 2013/14) equilibrium line altitude (ELA) and glacier-wide mass loss. The result indicates that even at 6000 m above sea level (a.s.l.), the annual mass loss reaches ~0.73 m water equivalent (w.e.) during the past 9 years. Concordant with the abrupt climate shift in the end of 1980s, the ELA has dramatically risen from ~5969 +/- 73 m a.s.l. during 1973/74-1988/89 to ~6193 +/- 75 m a.s.l. during 1989/90-2013/14, suggesting that future ice cores containing uninterrupted climate records could only be recovered at least above 6200 m a.s.l. in the Naimona'nyi region. The glacier-wide mass balance over the past 41 years is averaged to be approximately -0.40 +/- 0.17 m w.e., exhibiting a significant increase in the decadal average from -0.01 +/- 0.15 to -0.69 +/- 0.21 m w.e. PMID- 27561414 TI - Prognostic Significance of Mixed-Lineage Leukemia (MLL) Gene Detected by Real Time Fluorescence Quantitative PCR Assay in Acute Myeloid Leukemia. AB - BACKGROUND The overall prognosis of acute myeloid leukemia (AML) patients with mixed-lineage leukemia (MLL) gene-positivity is unfavorable. In this study, we evaluated the expression levels of the MLL gene in AML patients. MATERIAL AND METHODS We enrolled 68 MLL gene-positive patients out of 433 newly diagnosed AML patients, and 216 bone marrow samples were collected. Real-time fluorescence quantitative PCR (RQ-PCR) was used to precisely detect the expression levels of the MLL gene. RESULTS We divided 41 patients into 2 groups according to the variation of MRD (minimal residual disease) level of the MLL gene. Group 1 (n=22) had a rapid reduction of MRD level to <=10^-4 in all samples collected in the first 3 chemotherapy cycles, while group 2 (n=19) had MRD levels constantly >10^ 4 in all samples collected in the first 3 chemotherapy cycles. Group 1 had a significantly better overall survival (p=0.001) and event-free survival (p=0.001) compared to group 2. Moreover, the patients with >10^-4 MRD level before the start of HSCT (hematopoietic stem cell transplantation) had worse prognosis and higher risk of relapse compared to patients with <=10^-4 before the start of HSCT. CONCLUSIONS We found that a rapid reduction of MRD level to <=10^-4 appears to be a prerequisite for better overall survival and event-free survival during the treatment of AML. The MRD levels detected by RQ-PCR were basically in line with the clinical outcome and may be of great importance in guiding early allogeneic HSCT (allo-HSCT) treatment. PMID- 27561413 TI - Eye fixation during multiple object attention is based on a representation of discrete spatial foci. AB - We often look at and attend to several objects at once. How the brain determines where to point our eyes when we do this is poorly understood. Here we devised a novel paradigm to discriminate between different models of spatial selection guiding fixation. In contrast to standard static attentional tasks where the eye remains fixed at a predefined location, observers selected their own preferred fixation position while they tracked static targets that were arranged in specific geometric configurations and which changed identity over time. Fixations were best predicted by a representation of discrete spatial foci, not a polygonal grouping, simple 2-foci division of attention or a circular spotlight. Moreover, attentional performance was incompatible with serial selection. Together with previous studies, our findings are compatible with a view that attentional selection and fixation rely on shared spatial representations and suggest a more nuanced definition of overt vs. covert attention. PMID- 27561415 TI - Effect of Vitamin D and calcium supplementation on ischaemic stroke outcome: a randomised controlled open-label trial. AB - BACKGROUND AND AIMS: Vitamin D deficiency is a common problem in stroke survivors. Observational studies have reported an association of low vitamin D levels with greater stroke severity, poststroke mortality and functional disability. Randomised clinical trials are lacking. We sought to assess the effect of calcium and vitamin D supplementation in ischaemic stroke survivors with vitamin D deficiency/insufficiency on disability/mortality outcomes. METHODS: In this randomised controlled open-label trial, 73 patients of acute ischaemic stroke were screened for serum 25 hydroxy Vitamin D (25(OH)D) levels. A total of 53 patients with baseline 25(OH)D <75 nmol/L were randomised into two arms. One received vitamin D and calcium supplementation along with usual care (n=25) and the other received usual care alone (n=28). Primary outcome was the proportion of patients achieving a good outcome [modified Rankin Scale score 0-2] at 6 months and all cause mortality at 6 months. RESULTS: The age (mean+/-SD) of participants was 60.4+/-11.3 years, 69.8% were males. The proportion of patients achieving good outcome was higher in the intervention arm (Adjusted OR 1.9, 95% CI 0.6-6.4; P=.31). The survival probability was greater in the intervention arm (83.8%, CI 62.4-93.6) as compared with the control arm (59.5%, CI 38.8-75.2; P=.049) with adjusted Hazard ratio (HR) of 0.26 (95% CI 0.08-0.9; P=.03). CONCLUSIONS: This is the first randomised controlled study assessing the effect of vitamin D and calcium supplementation on ischaemic stroke outcomes and points towards a potential benefit. Findings need to be validated by a larger trial. PMID- 27561416 TI - This baby is not for turning: Women's experiences of attempted external cephalic version. AB - BACKGROUND: Existing studies regarding women's experiences surrounding an External Cephalic Version (ECV) report on women who have a persistent breech post ECV and give birth by caesarean section, or on women who had successful ECVs and plan for a vaginal birth. There is a paucity of understanding about the experience of women who attempt an ECV then plan a vaginal breech birth when their baby remains breech. The aim of this study was to examine women's experience of an ECV which resulted in a persistent breech presentation. METHODS: A qualitative descriptive exploratory design was undertaken. In-depth semi structured interviews were conducted and analysed thematically. RESULTS: Twenty two (n = 22) women who attempted an ECV and subsequently planned a vaginal breech birth participated. Twelve women had a vaginal breech birth (55 %) and 10 (45 %) gave birth by caesarean section. In relation to the ECV, there were five main themes identified: 'seeking an alternative', 'needing information', 'recounting the ECV experience', 'reacting to the unsuccessful ECV' and, 'reflecting on the value of an ECV'. CONCLUSIONS: ECV should form part of a range of options provided to women, rather than a default procedure for management of the term breech. For motivated women who fit the safe criteria for vaginal breech birth, not being subjected to a painful experience (ECV) may be optimal. Women should be supported to access services that support vaginal breech birth if this is their choice, and continuity of care should be standard practice. PMID- 27561419 TI - Management of gallstone pancreatitis in the vagrant liver. PMID- 27561417 TI - Chlamydia trachomatis infection and Vgamma9Vdelta2 Tau cells in women with recurrent spontaneous abortions. AB - PROBLEM: Vgamma9Vdelta2 T cells (gamma9delta2) are involved in antibacterial immune responses. The aim of this study was to look for associations between peripheral blood (PB) gamma9delta2 T cells and cervix/vaginal Chlamydia trachomatis (Ct) infection in women with recurrent spontaneous abortions (RSA). METHOD OF STUDY: Peripheral blood samples were obtained from 201 RSA women within 10 days after they experienced a new miscarriage. gamma9delta2 T cells and their percentage in total gammadelta T cells were compared between women who had been found and women who had not been found infected with Ct (last 6 months). Fertile women (82) served as control subjects. RESULTS: The difference of mean percentages of gamma9delta2 T cells between the abortion and control groups, and the Chlamydia (+) and Chlamydia (-) groups was highly statistically significant (P<.00001). Significant difference was also found between the Chlamydia (+) and Chlamydia (-) group and the control group (ANOVA). CONCLUSION: The measurement of gamma9delta2T cells may be useful to suspect possibly undiagnosed chlamydial infection in RSA women. PMID- 27561420 TI - A prospective randomised study of a rigid video-stylet vs. conventional lightwand intubation in cervical spine-immobilised patients. AB - Compared with a lightwand which is used blind, OptiscopeTM , a rigid video stylet, can provide direct imaging of airway structures, potentially offering improved conditions in cervical spine-immobilised patients. We randomly assigned 168 patients who required cervical immobilisation during tracheal intubation to use of the Optiscope or the lightwand. The initial intubation success rate (95% CI) was 90 (82-95)% with the Optiscope and 87 (78-93)% with the lightwand (p = 0.626). Median (IQR [range]) intubation time was longer (19 (12-41 [5-195] s vs. 15 (8-29 [3-117] s; p = 0.016), and there were fewer scooping movements (1 (1-2 [0-9]) vs. 2 (1-3 [0-14]); p = 0.002) when using the Optiscope compared with the lightwand. The incidence of postoperative airway complications was similar in the two groups. The devices were equivalent with respect to initial intubation success rate but the Optiscope yielded slightly longer intubating times. PMID- 27561421 TI - Principles of cardiovascular magnetic resonance feature tracking and echocardiographic speckle tracking for informed clinical use. AB - Tissue tracking technology of routinely acquired cardiovascular magnetic resonance (CMR) cine acquisitions has increased the apparent ease and availability of non-invasive assessments of myocardial deformation in clinical research and practice. Its widespread availability thanks to the fact that this technology can in principle be applied on images that are part of every CMR or echocardiographic protocol. However, the two modalities are based on very different methods of image acquisition and reconstruction, each with their respective strengths and limitations. The image tracking methods applied are not necessarily directly comparable between the modalities, or with those based on dedicated CMR acquisitions for strain measurement such as tagging or displacement encoding. Here we describe the principles underlying the image tracking methods for CMR and echocardiography, and the translation of the resulting tracking estimates into parameters suited to describe myocardial mechanics. Technical limitations are presented with the objective of suggesting potential solutions that may allow informed and appropriate use in clinical applications. PMID- 27561423 TI - Reply. PMID- 27561422 TI - The transcriptional and splicing landscape of intestinal organoids undergoing nutrient starvation or endoplasmic reticulum stress. AB - BACKGROUND: The intestinal epithelium plays a critical role in nutrient absorption and innate immune defense. Recent studies showed that metabolic stress pathways, in particular the integrated stress response (ISR), control intestinal epithelial cell fate and function. Here, we used RNA-seq to analyze the global transcript level and alternative splicing responses of primary murine enteroids undergoing two distinct ISR-triggering stresses, endoplasmic reticulum (ER) stress and nutrient starvation. RESULTS: Our results reveal the core transcript level response to ISR-associated stress in murine enteroids, which includes induction of stress transcription factors, as well as genes associated with chemotaxis and inflammation. We also identified the transcript expression signatures that are unique to each ISR stress. Among these, we observed that ER stress and nutrient starvation had opposite effects on intestinal stem cell (ISC) transcriptional reprogramming. In agreement, ER stress decreased EdU incorporation, a marker of cell proliferation, in primary murine enteroids, while nutrient starvation had an opposite effect. We also analyzed the impact of these cellular stresses on mRNA splicing regulation. Splicing events commonly regulated by both stresses affected genes regulating splicing and were associated with nonsense-mediated decay (NMD), suggesting that splicing is modulated by an auto regulatory feedback loop during stress. In addition, we also identified a number of genes displaying stress-specific splicing regulation. We suggest that functional gene expression diversity may arise during stress by the coordination of alternative splicing and alternative translation, and that this diversity might contribute to the cellular response to stress. CONCLUSIONS: Together, these results provide novel understanding of the importance of metabolic stress pathways in the intestinal epithelium. Specifically, the importance of cellular stresses in the regulation of immune and defense function, metabolism, proliferation and ISC activity in the intestinal epithelium is highlighted. Furthermore, this work highlights an under-appreciated role played by alternative splicing in shaping the response to stress and reveals a potential mechanism for gene regulation involving coupling of AS and alternative translation start sites. PMID- 27561424 TI - Reply. PMID- 27561425 TI - What gets passed in "Chunk-and-Pass" processing? A predictive processing solution to the Now-or-Never bottleneck. AB - I agree with the existence, and importance, of the "Now-or-Never" bottleneck. However, there is a far simpler and more parsimonious solution to it. This solution is predictive processing, and the failure to view the solution that this provides fundamentally boils down to viewing prediction as one aspect of cognition, rather than as its central principle. PMID- 27561426 TI - Clinical proteomics in cancer: Where we are. AB - Proteomics has emerged as a promising field in the post-genomic era. Notwithstanding the great advances provided by gene expression analysis in cancer, the lack of a correlation between gene expression and protein levels has highlighted the need for a proteomic focus on cancer. Although the increasing knowledge regarding cancer biology, a reliable marker to improve diagnosis, prognosis and treatment for cancer patients is not a reality at present. In this review, we address the main considerations regarding proteomics-based studies and their clinical applications on cancer research, highlighting some considerations related to strengths and limitations of proteomics-based studies and its application to clinical practice. PMID- 27561427 TI - Detection of Circulating Auto-Antibodies Against Ribosylated-LDL in Diabetes Patients. AB - BACKGROUND: This study analyzes effect of glycation on ApoB-100 residues by D ribose as D-ribosylated-glycated LDL might be responsible for the cause of diabetes mellitus because of its far higher antigenic ability. The binding characteristics of circulating auto-antibodies in type 1 and type 2 diabetes patients against native and modified LDL were assessed. METHODS: T1 Diabetes (n = 43), T2 diabetes patients (n = 100) were examined by direct binding ELISA as well as inhibition ELISA, were compared with healthy age-matched controls (n = 50). RESULTS: High degree of specific binding was observed by 74.42% of T1 diabetes and 45.0% of T2 diabetes patient's sera toward glycated LDL, in comparison to its native analog. Competitive inhibition ELISA reiterates the direct binding results. Furthermore, ketoamine content, Hydroxymethylfurfural (HMF) content and carbonyl content were also estimated in patient's sera healthy subjects. The increase in total serum protein carbonyl levels in the diabetes patients was largely due to an increase in oxidative stress. The increase in ketoamine as well as HMF content inpatients sera than healthy subjects is an agreement of induced glycation reaction in patients than healthy subjects. CONCLUSION: D-ribosylated LDL has resulted in structural perturbation causing generation of neo-antigenic epitopes that are better antigens for antibodies in T1 and T2 diabetes patients. PMID- 27561428 TI - Synthesis and comparative in vivo evaluation of 99m Tc(CO)3 -labeled PEGylated and non-PEGylated cRGDfK peptide monomers. AB - This work aimed at studying the effect of insertion of medium PEG (PEG7 ) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non-PEGylated analogue. The cRGDfK peptide has thus been derivatized at epsilon-amino group of lysine by conjugation with N3 -PEG7 -COOH/N3 -CH2 -COOH to prepare a PEGylated and a non-PEGylated analogue of cRGDfK. A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [99m Tc(CO)3 (H2 O)3 ]+ precursor. Comparative in vivo evaluation of the two 99m Tc(CO)3 -labeled radiotracers, 99m Tc(CO)3 -Pra-Tz-CH2 cRGDfK 5 and 99m Tc(CO)3 -Pra-Tz-PEG7 -cRGDfK 6, was carried out in C57BL/6 mice bearing alphav beta3 -positive melanoma tumors to determine their potential toward targeting integrin alphav beta3 receptors. The radiotracers exhibited excellent stability in saline as well as in serum. Maximum tumor uptake for the two radiotracers was observed at 30 min p.i. (5: 3.0 +/- 0.7% ID/g; 6: 4.1 +/- 0.5% ID/g). The two neutral 99m Tc(CO)3 radiotracers prepared exhibited receptor mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG7 unit was accompanied by slower clearance from other organs which resulted in decreased target-to-background ratios. The in vivo kinetics of 99m Tc(CO)3 -labeled radiotracer, 99m Tc(CO)3 -Pra-Tz-CH2 -cRGDfK 5 with only methylene unit as the spacer, was found to be more favorable due to higher tumor/blood, tumor/liver, tumor/kidney, and tumor/lung ratios. PMID- 27561429 TI - Dermal patch graft correction of severe chordee secondary to penile corporal body disproportion without urethral division in boys without hypospadias. AB - Historically, significant ventral penile curvature secondary to corporal body disproportion has been corrected either by dorsal plication or division of the urethral plate. In the rare situations where there is severe chordee in the face of an intact urethra with an orthotopic meatus, division of the urethral plate is commonly performed at the time of grafting the ventral defect created by incising the tunica albuginea. Subsequently, a staged procedure is necessary to reconnect the urethra at a later date. Herein the authors present a novel technique that shows it is possible to perform successful dermal patch orthoplasty without division of the urethra in patients with a normal orthotopic meatus and urethra via urethral mobilization. Three patients over the past 3 years with severe ventral chordee, orthotopic meati and normal urethral anatomy presented for correction. Two patients were 18 years old and one was 10 years old. All three boys were circumcised. The two older boys insisted on dorsal plication as a first approach which worked only temporarily for about 6 months while the younger boy had no prior surgery performed. Each boy underwent a circumcising incision, degloving of the shaft skin, extensive urethral mobilization and dermal patch graft orthoplasty to correct chordee. All surgeries were performed in an outpatient setting. No urinary drainage was used in any patient and a simple bio occlusive dressing was employed in each case. Follow-up ranged from 11 months to 2 years (mean 1.5 years). All three boys have strong straight erections, full well directed urinary streams and no complications noted to date. Our conclusion based on this experience is that extensive urethral mobilization can allow for correction of severe ventral chordee without urethral division in a single operative setting in boys without hypospadias and a normal urethra. The accompanying movie herein describes the surgical technique. PMID- 27561430 TI - Natural language processing and the Now-or-Never bottleneck. AB - Researchers, motivated by the need to improve the efficiency of natural language processing tools to handle web-scale data, have recently arrived at models that remarkably match the expected features of human language processing under the Now or-Never bottleneck framework. This provides additional support for said framework and highlights the research potential in the interaction between applied computational linguistics and cognitive science. PMID- 27561431 TI - The paradox of decreasing nonmedical opioid analgesic use and increasing abuse or dependence - An assessment of demographic and substance use trends, United States, 2003-2014. AB - BACKGROUND: The harms related to nonmedical use of opioid analgesics have impacted the United States for more than a decade. Examining trends in nonmedical use, abuse, and dependence among various demographic and substance using groups can provide critical insight for prevention and treatment activities. METHODS: Data from the National Survey on Drug Use and Health were used to assess trends in opioid analgesic nonmedical use, abuse, and dependence for 2003-2005, 2006 2008, 2009-2011, and 2012-2014. Multivariable logistic regression was used to identify characteristics associated with opioid analgesic abuse or dependence. RESULTS: Rates of past-year opioid analgesic nonmedical use decreased from 48.4 per 1000 persons aged 12years and older in 2003-2005 to 43.3 in 2012-2014. Declines were seen among most demographic and substance using groups. In contrast, rates of past-year opioid analgesic abuse or dependence increased from 6.0 per 1000 persons in 2003-2005 to 7.5 in 2012-2014; increases were seen among most demographic and substance using groups. In 2012-2014, odds of opioid analgesic abuse or dependence were highest among those with sedative or tranquilizer and heroin abuse or dependence. CONCLUSIONS: These findings indicate encouraging trends in overall nonmedical use of opioid analgesics which declined among many demographic and substance using groups. However, continued increases in rates of opioid analgesic abuse or dependence highlight the critical importance of maintaining efforts to drive down inappropriate opioid prescribing and expanding efforts to increase the provision of medication assisted treatment and psychosocial services for opioid use disorders and equipping individuals with naloxone to reverse opioid overdose. PMID- 27561432 TI - Diversion of prescription stimulants among college students: An initial investigation of injunctive norms. AB - Nonmedical use of prescription stimulants (NMUPS) is an increasing problem among the college student population. Despite recent increases in stimulant prescriptions, little research has examined diversion of prescription stimulants among college students. The purpose of the current exploratory study was to compare normative beliefs about the frequency and motives of NMUPS among a college student sample. Participants were 121 college students who reported having a current prescription for a prescription stimulant. Participants completed online surveys and reported occasions of diversion behavior along with ratings of perceived approval for NMUPS and associated motives. Participants with a history of diversion were more likely to rate their close friends as more approving of more frequent NMUPS, and more approving of various motives for NMUPS. Perceived approval of NMUPS and NMUPS motives among parents and typical university students was similar across diversion groups, with parents and university students being rated as more approving of NMUPS for educational purposes. These findings extend the use of social norms theory to a new behavior while adding to our understanding how those who divert their medication differ from those who do not. Future studies should seek to establish a causal relationship between perceived approval for NMUPS and diversion behaviors. These findings also suggest that future research should focus on the feasibility and impact of social norms intervention for NMUPS and medication diversion. PMID- 27561433 TI - Assessment of terminal cleaning in pediatric isolation rooms: Options for low resource settings. AB - BACKGROUND: Few studies have evaluated terminal cleaning in low-resource settings. METHODS: Adequacy of pediatric isolation room terminal cleaning was evaluated using quantitative bacterial surface cultures, ATP bioluminescence assays, and fluorescent high-touch surface markers at Tygerberg Children's Hospital in South Africa (August 1, 2014-October 31, 2015). Cleaning adequacy was assessed by comparing pre- and postcleaning measurements. Influence of verbal feedback was determined by comparing cleaners' first and subsequent cleaning episodes. Cleaning methods were compared for cost, time, and feasibility. RESULTS: Adequacy of terminal cleaning was evaluated in 25 isolation rooms after hospitalization for pulmonary tuberculosis (n = 13), respiratory (n = 5) and enteric viruses (n = 5), pertussis (n = 1), and methicillin-resistant Staphylococcus aureus (n = 1). Mean aerobic colony counts and mean ATP relative light units declined between pre- and postcleaning evaluations (39 +/- 41 to 15 +/- 30 [P < .001] and 72 +/- 40 to 23 +/- 11 [P < .001]). Fluorescent marker removal was initially poor, but improved significantly at subsequent cleaning episodes (17 out of 78 [22%] to 121 out of 198 [61%]; P < .001); mean aerobic colony counts and ATP values also declined significantly following feedback. Cost, time, and resources required for ATP and surface cultures far exceeded that required for fluorescent markers. CONCLUSIONS: Adequacy of isolation room cleaning improved following feedback to cleaning staff. Fluorescent markers are an inexpensive option for cleaning evaluation and training in low-resource settings. PMID- 27561434 TI - Reduction in bacterial contamination of hospital textiles by a novel silver-based laundry treatment. AB - Treating hospital patient textiles with ionic silver after each washing results in a significant decrease in microbial contamination. Although further study is needed to better understand the role textiles play in hospital-acquired infections and to quantify the influence of silver textile treatment on health care-associated infection risk and patient outcomes, ionic silver treatment of textiles may prove useful in hospital-acquired infection reduction strategies. PMID- 27561435 TI - Is airborne transmission of Acinetobacter baumannii possible: A prospective molecular epidemiologic study in a tertiary care hospital. AB - BACKGROUND: Understanding the dynamics of aerial spread of Acinetobacter may provide useful information for production of effective control measurements. We investigated genetic relationships between air and clinical isolates of Acinetobacter baumannii in an intensive care unit (ICU) setting. METHODS: We conducted a prospective surveillance study in a tertiary care hospital for 8 months. A total of 186 air samples were taken from 2 ICUs. Clonal characteristics of air isolates were compared with the prospective clinical strains and the previously isolated strains of ICU patients over a 23-month period. RESULTS: Twenty-six (11.4%) air samples yielded A baumannii, of which 24 (92.3%) isolates were carbapenem-resistant. The Acinetobacter concentration was the highest in bedside sampling areas of infected patients (0.39 CFU/m3). Air isolates were clustered in 13 genotypes, and 7 genotypes (including 18 air strains) were clonally related to the clinical strains of 9 ICU patients. One clone continued to be cultured over 27 days in ICU air, and air isolates could be clonally related to 7-week retrospective and approximately 15-week prospective clinical strains. CONCLUSIONS: The results of this study suggest that infected patients could spread significant amounts of Acinetobacter to ICU air. These strains could survive in air for some weeks and could likely still infect new patients after some months. Special control measurements may be required against the airborne spread of Acinetobacter in ICUs. PMID- 27561436 TI - Mind, brain, and teaching: Some directions for future research-CORRIGENDUM. PMID- 27561437 TI - Neurometabolic disorders are treatable causes of dystonia. AB - A broad range of rare inherited metabolic disorders can present with dystonia. For clinicians, it is important to recognize dystonic features, but it can be complicated by the mixed and complex clinical picture seen in many neurometabolic patients. Careful phenotyping is the first step towards the diagnosis of the underlying condition and subsequent targeted treatment, further supported by imaging, biochemical diagnostics and the availability of modern diagnostic techniques such as next generation sequencing. As several neurometabolic disorders are treatable causes of dystonia, these should have priority in the diagnostic process. In the symptomatic treatment of dystonia, several therapeutic options are available. Awareness for the occurrence and optimal treatment of dystonia and other movement disorders in neurometabolic conditions is important because these symptoms can have a substantial impact on the quality of life and daily functioning; this effect is not only exerted by the dystonia itself, but also by the frequently associated non-motor features. In this paper, the highlights and key concepts of neurometabolic forms of dystonia are discussed, with a focus on phenomenology, the diagnostic approach, the most important neurometabolic aetiologies, co-occurring non-motor features and therapeutic options. PMID- 27561438 TI - Progressive supranuclear palsy and corticobasal degeneration: Diagnostic challenges and clinicopathological considerations. AB - Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future. PMID- 27561439 TI - Essential tremor: Update of therapeutic strategies (medical treatment and gamma knife thalamotomy). AB - Tremor is a highly prevalent movement disorder that markedly reduces quality of life. The management of severe tremor is particularly challenging. Pharmacological treatment is available, but no real breakthrough has emerged recently. Propranolol and primidone are still the two most recommended agents, followed by topiramate. However, surgical treatments for medically refractory tremors are expanding. Gamma knife (GK) thalamotomy is an option particularly suitable for patients who are not candidates for deep brain stimulation. Owing to the fact that it is a non-invasive procedure without craniotomy, GK radiosurgery has almost no contraindications. Since the late 1990s, more than 250 case reports and patient series have been published. Most of these studies show that unilateral GK thalamotomy is well tolerated and reduces tremor disability. A recent study with prospective blinded assessment has confirmed its safety, together with significant improvements in tremor scores and activities of daily living. PMID- 27561440 TI - Guidelines for clinical pharmacological practices in Huntington's disease. AB - OBJECTIVE: Evidence-based medicine is a difficult goal to achieve in rare diseases where randomized controlled trials are lacking. This report provides guidelines that capitalize on both the literature and expertise of the French National Huntington Disease Reference Centre to optimalize pharmacological therapeutic interventions for Huntington's disease (HD). MATERIAL AND METHODS: HD experts conducted a systematic analysis of the literature from 1965 to 2013, using a scoring procedure established by the French National Authority for Health. These experts offered their views when evidence was missing to set up provisional guidelines for care in HD. These guidelines were then scored and amended through two subsequent online questionnaires (using SurveyMonkey(r) scoring), and one face-to-face meeting with an external multidisciplinary working group as a step towards validation. RESULTS: Except for the beneficial effects of tetrabenazine in chorea, none of the published recommendations were grounded on established scientific evidence. Second-generation antipsychotics are nevertheless the first choice for patients with psychiatric manifestations (low level of evidence). All other guidelines are based on low-level evidence and little professional agreement. CONCLUSION: Patients' care has greatly improved over the last few years despite the lack of high-level evidence standards. Guidelines are based on the expertise of trained specialists from the French National Plan for Rare Diseases. This strategy should now be extended internationally to promote future studies and to harmonize worldwide care of HD. PMID- 27561441 TI - Current concepts of essential tremor. AB - Essential tremor is clinically defined but there is increasing evidence that it is not a unique entity. Its pathophysiology has been studied with many methods but may also vary between subtypes. Neurophysiologically, there is strong evidence that a specific cerebello-thalamo-cortical loop is abnormally oscillating. The cause of its uncontrolled oscillation is not yet understood. The clear proof of a degenerative cause is still lacking and abnormal receptors or other causes of altered non-progressive functional disturbance cannot be excluded. Strong evidence supports the major involvement of the cerebellum and there is ample evidence that GABA is the main neurotransmitter involved in the pathophysiology in ET. Genetics have provided so far only a few rare subtypes which are due to specific mutations but there is no doubt that it is mostly a hereditary condition. There is evidence that the large subgroup of late onset tremor is a separate condition and this tremor is an independent risk factor for earlier mortality and comes with signs of premature aging (aging-related tremor). It will be important to improve phenotyping of patients in more detail possibly to include not only features of the tremor itself but also other clinical assessments like force measurements or cognitive testing. Based on these variables, we may be able to better understand the presumably different mechanisms underlying different variants of the disease. PMID- 27561442 TI - The role of cell adhesion molecules in brain wiring and neuropsychiatric disorders. AB - Cell adhesion molecules (CAMs) in the nervous system have long been a research focus, but many mice lacking CAMs show very subtle phenotypes, giving an impression that CAMs may not be major players in constructing the nervous system. However, recent human genetic studies suggest CAM involvement in many neuropsychiatric disorders, implicating that they must have significant functions in nervous system development, namely in circuitry formation. As CAMs can provide specificity through their molecular interactions, this review summarizes possible mechanisms on how alterations of CAMs can result in neuropsychiatric disorders through circuitry modification. PMID- 27561443 TI - Label-free fluorometric detection of chymotrypsin activity using graphene oxide/nucleic-acid-stabilized silver nanoclusters hybrid materials. AB - Pancreatic function tests are used to determine the presence of chronic pancreatitis, particularly in the early stage of the disease. Chymotrypsin is an indicator of pancreatic function and is thus related to pancreatic diseases. A new fluorescent biosensing method for assay of chymotrypsin activity was developed using DNA (dC12)-templated silver nanoclusters and graphene oxide (GO). A peptide probe was also designed using chymotrypsin-cleavable amino acid sequence and a cysteine terminus. The peptide probe formed Ag-S bond to dC12 AgNCs to enhance the fluorescence of dC12-AgNCs. After the addition of GO, the peptide was adsorbed to the negative GO surface and the fluorescence of dC12 AgNCs was quenched by FRET. The peptide was then degraded into amino acid fragments upon addition of chymotrypsin; these fragments were released from the GO surface, and the FRET was terminated. The developed label-free method features lower cost and higher sensitivity to chymotrypsin activity assay compared with conventional fluorescence analysis. The method can be used to analyze chymotrypsin (as low as 3ng/mL, signal/noise =3) across a dynamic range of 0.0 50.0ng/mL. The proposed biosensing strategy can also be extended to other proteases by using different peptide substrates. PMID- 27561444 TI - Do-Not-Attempt-Resuscitation orders for people with intellectual disabilities: dilemmas and uncertainties for ID physicians and trainees. The importance of the deliberation process. AB - BACKGROUND: Not much is known about Do-Not-Attempt-Resuscitation (DNAR) decision making for people with intellectual disabilities (IDs). The aim of this study was to clarify the problems and pitfalls of non-emergency DNAR decision-making for people with IDs, from the perspective of ID physicians. METHODS: This qualitative study was based on semi-structured individual interviews, focus group interviews and an expert meeting, all recorded digitally and transcribed verbatim. Forty ID physicians and trainees were interviewed about problems, pitfalls and dilemmas of DNAR decision-making for people with IDs in the Netherlands. Data were analysed using Grounded Theory procedures. RESULTS: The core category identified was 'Patient-related considerations when issuing DNAR orders'. Within this category, medical considerations were the main contributory factor for the ID physicians. Evaluation of quality of life was left to the relatives and was sometimes a cause of conflicts between physicians and relatives. The category of 'The decision maker role' was as important as that of 'The decision procedure in an organisational context'. The procedure of issuing a non-emergency DNAR order and the embedding of this procedure in the health care organisation were important for the ID physicians. CONCLUSION: The theory we developed clarifies that DNAR decision-making for people with IDs is complex and causes uncertainties. This theory offers a sound basis for training courses for physicians to deal with uncertainties regarding DNAR decision-making, as well as a method for advance care planning. Health care organisations are strongly advised to implement a procedure regarding DNAR decision-making. PMID- 27561445 TI - Complications causing patients to discontinue using oral appliances for treatment of obstructive sleep apnea. AB - PURPOSE: Oral appliances (OAs) are commonly used as a noninvasive treatment for obstructive sleep apnea syndrome (OSAS). These devices are worn during sleep and create mandibular anterior traction to enlarge the upper airway. Continuous use of the device is essential for the success of OA therapy, but some patients stop using the OA for various reasons. The purpose of this research was to investigate complications in OA therapy that might prevent continuous use of these devices. METHODS: The progress of 90 OSAS patients who visited Tokushima University Hospital and underwent OA therapy was investigated with a mailed questionnaire. All patients had been receiving OA therapy for more than 12 months. RESULTS: Forty patients responded to the questionnaire and of these, 22 were not wearing their OA during sleep. The average period before stopping OA therapy was 9.6 months. Answers from 38 patients who were treated with two-piece Herbst(r)-type oral appliances were analyzed. The main reasons for stopping OA therapy were: (1) it was bothersome to use; and (2) it did not effectively prevent sleep apnea. Comparison of OA complications between current OA users and nonusers revealed significant differences for the items "difficulty sleeping" and "stifling feeling". OA users recorded better scores for sleep quality than nonusers. CONCLUSIONS: The results of this study indicate that patients discontinued OA therapy because the appliance was "bothersome to use" and because it had "little or no effect" rather than because they experienced the typical complications of OA therapy. PMID- 27561446 TI - Unique Crystallization of Fullerenes: Fullerene Flowers. AB - Solution-phase crystallization of fullerene molecules strongly depends on the types of solvent and their ratios because solvent molecules are easily included in the crystal lattice and distort its structure. The C70 (solute)-mesitylene (solvent) system yields crystals with various morphologies and structures, such as cubes, tubes, and imperfect rods. Herein, using C60 and C70 dissolved in mesitylene, we present a novel way to grow unique flower-shaped crystals with six symmetric petals. The different solubility of C60 and C70 in mesitylene promotes nucleation of C70 with sixfold symmetry in the early stage, which is followed by co-crystallization of both C60 and C70 molecules, leading to lateral petal growth. Based on the growth mechanism, we obtained more complex fullerene crystals, such as multi-deck flowers and tube-flower complexes, by changing the sequence and parameters of crystallization. PMID- 27561447 TI - Clarifying the time frame and units of selection in the cultural group selection hypothesis. AB - We raise and discuss two issues for clarification. First, over what timescale is cultural group selection proposed to have been active? Unprecedented cooperation is inferred to have arisen in hunter-gather life well before the recent period on which Richerson et al. FOCUS: Second, what is the unit of selection? Groups (of human individuals)? Or cultural entities along the lines of "meme-complexes"? PMID- 27561448 TI - Health or harm? A cohort study of the importance of job quality in extended workforce participation by older adults. AB - BACKGROUND: As people are living longer, they are being encouraged to work longer. While it is assumed that extended employment will be good for health, the evidence has been mixed. This study considers whether employment and job quality exert an influence on four indicators of health status in older workers. METHODS: Data for this study came from 836 older workers (440 men and 396 women) aged 50 59 years at baseline who participated in the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Using linear regression, we examine within person change in self-rated, physical and mental health and one health behaviour (physical activity) at two time points over a nine year follow-up period. RESULTS: There were minimal differences in the way health changed for older adults who continued working compared to those who retired voluntarily. However, when we decomposed employment in terms of job quality, health outcomes diverged. Compared to voluntary retirees, older workers who had worked in good quality jobs reported marginally better self-rated health (0.14,-0.02-0.29); but did not differ in their physical (2.31,-1.09-5.72) or mental health (0.51,-1.84-2.87). In contrast, older workers who held poor quality jobs for most of the follow-up period declined in their self-rated (-1.13,-0.28 - -0.02), physical (-4.90, 8.52- - 1.29) and mental health (-4.67, 7.69- - 1.66) relative to voluntary retirees. Older workers who held poor quality jobs for just some of the follow-up period did not differ from voluntary retirees in terms of their health. However there was evidence of a linear relationship between length of exposure to poor quality jobs and decline in health outcomes. CONCLUSION: Extended working lives mean that people will be 'exposed' to work for longer, and this exposure will occur at a life stage characterised by declining health for many. Our findings show that ensuring older workers have access to secure jobs which allow for control over work time, skill use and fair rewards will be essential if policy goals to boost participation and productivity, as well as reduce the health and care costs of the elderly, are to be met. PMID- 27561450 TI - Does cultural group selection explain the evolution of pet-keeping? AB - Pet-keeping is highly variable across cultures in both frequency and form. Cultural group selection offers a plausible explanation for the development and spread of this uniquely human phenomenon in that pet-keeping involves an inheritance system, socially transmitted norms and preferences, substantial between-group variation, and (albeit indirectly) intergroup competition. PMID- 27561449 TI - Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG). AB - Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK- and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (>=5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK- but not in MK+ group. In conclusion, concomitance of MK with >=5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+. PMID- 27561451 TI - Improved Ambient-Stable Perovskite Solar Cells Enabled by a Hybrid Polymeric Electron-Transporting Layer. AB - In this work, an efficient inverted perovskite solar cell with decent ambient stability is successfully demonstrated by employing an n-type polymer, poly{[N,N' bis(2-octyldodecyl)-1,4,5,8-naphthalene diimide-2,6-diyl]-alt-5,5'-(2,2' bithiophene)} (N2200), as the electron-transporting layer (ETL). The device performance can be further enhanced from a power conversion efficiency (PCE) of 15 to 16.8 % by tailoring the electronic properties of N2200 with a polymeric additive, poly[9,9-bis(6'-(N,N-diethylamino)propyl)-fluorene-alt-9,9-bis(3 ethyl(oxetane-3-ethyloxy)-hexyl) fluorene] (PFN-Ox). More importantly, the device derived from this hybrid ETL can maintain good ambient stability inherent from the pristine N2200 ETL, for which 60-70 % of initial PCE can be retained after being stored in air with 10-20 % humidity for 45 days. PMID- 27561452 TI - Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO. AB - OBJECTIVES: We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients < and >40 years of age with advanced epithelial ovarian cancer. METHODS: A total of 5055 patients of the AGO, GINECO, NSGO intergroup studies AGO-OVAR 3, 5, 7 and 9 were merged to identify 294 patients <40 years and 4761 patients >=40 years. We conducted survival analyses and Cox proportional hazard regression models and additionally analysed a very homogeneous subcohort of 405 patients with serous epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and >=5 chemotherapy cycles. RESULTS: For patients <40 years, the median PFS was 28.9 months and the median OS was 75.3 months, while the median PFS for patients >=40 years was 18.1 months and the median OS was 45.7 months. Independent prognostic factors were similar in both age groups. In a multivariate analysis including prognostic factors potentially leading to confounding, young age appeared to improve PFS (hazard ratio [HR], 0.86; 95% confidence interval [CI]: 0.72-1.03) and OS (HR, 0.73; 95% CI: 0.59-0.91). The observed effect was even stronger in the subcohort of optimally treated patients with SEOC: PFS (HR, 0.34; 95% CI: 0.19-0.59) and OS (HR, 0.23; 95% CI: 0.09-0.56). DISCUSSION: Prognostic factors were similar in both age groups. Young age appeared a strong independent protective prognostic factor for PFS and OS in the subcohort. PMID- 27561454 TI - Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine. AB - Great research effort has been focused on elucidating the contribution of host genetic variability on pharmacological outcomes in cancer. Nuclear receptors have emerged as mediators between environmental stimuli and drug pharmacokinetics and pharmacodynamics. The pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors have been reported to regulate transcription of genes that encode drug metabolizing enzymes and transporters. Altered nuclear receptor expression has been shown to affect the metabolism and pharmacological profile of traditional chemotherapeutics and targeted agents. Accordingly, polymorphic variants in these genes have been studied as pharmacogenetic markers of outcome variability. This review summarizes the state of knowledge about the roles played by pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factor expression and genetics as predictive markers of anticancer drug toxicity and efficacy, which can improve cancer precision medicine. PMID- 27561453 TI - Blood B Lymphocyte Stimulator (BLyS)/BAFF levels may reflect natural immunity to HIV in highly exposed uninfected Beninese Commercial Sex Workers. AB - We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of "precursor" innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection. Therefore, we assessed blood BLyS levels and B-cell status in HIV highly-exposed commercial sex workers (CSWs) from Benin. We found blood BLyS levels of HIV uninfected CSWs were lower than those observed in both HIV-infected CSW and HIV uninfected non-CSW groups. Furthermore, levels of BLyS expression on blood T cells and monocytes were lower in HIV-uninfected CSWs when compared to HIV infected CSWs, but higher than those observed for HIV-uninfected non-CSWs. Concomitantly, HIV-infected CSWs presented a dysregulated blood B-cell compartment, characterized by increased total IgG1, increased frequencies of populations presenting immature and/or innate profiles and a higher ratio of IgG(+)/IgA(+) plasmablasts. In contrast, relatively low levels of BLyS in the blood of HIV-uninfected CSWs coincided with a rather preserved B-cell compartment. PMID- 27561455 TI - Increased homocysteine plasma level is associated with shortened prothrombin time in HIV-infected patients. AB - OBJECTIVE: To find factors associated with increased homocysteine plasma level in HIV-infected patients. METHODS: Cross-sectional study, carried out as a supplementary task to the standard care of HIV-infected patients. The possible association of increased homocysteine plasma level with blood analyses results was assessed with a multiple linear regression analysis, using the automatic linear modeling available in SPSS version 22. RESULTS: A total of 145 patients were included. Creatinine was higher than normal in 7 patients (5%), prothrombin time was shortened in 36 patients (25%), and a monoclonal gammopathy was detected in 2 patients (1%). In the regression analysis, an association was found between high homocysteine plasma level and the following variables: low prothrombin time (beta coefficient -0.286, confidence interval -1.1854 to -0.754, p < 0.001), high creatinine (coefficient 9.926, confidence interval 6.351-15.246, p < 0.001), low folic acid (coefficient -0.331, confidence interval -0-483 to -0.187, p < 0.001), and low vitamin B12 (coefficient -0.007, confidence interval -0.01 to -0.001, p = 0.005). CONCLUSION: An association was found between increased homocysteine plasma level and shortened prothrombin time. PMID- 27561456 TI - AIM 2 inflammasomes regulate neuronal morphology and influence anxiety and memory in mice. AB - Inflammasomes are the protein assemblies that consist of inflammasome sensors, adaptor apoptosis-associated speck-like proteins containing a CARD (ASC) and inflammasome caspase. Inflammasomes sense multiple danger signals via various inflammasome sensors and consequently use caspase to trigger proteolytic processing and secretion of IL-1beta cytokines. Recent studies have suggested that neurons use their own innate immune system to detect danger signals and regulate neuronal morphology. Here, we investigate whether inflammasomes, the critical components of innate immunity, participate in regulation of neuronal morphology and function. Among various sensors, Absent in melanoma 2 (Aim2) expression in neurons is most prominent. Adding synthetic double-stranded DNA (dsDNA) to cultured neurons induces IL-1beta secretion in an AIM2-dependent manner and consequently downregulates dendritic growth but enhances axon extension. The results of Aim2 knockout and knockdown show that AIM2 acts cell autonomously to regulate neuronal morphology. Behavioral analyses further reveal that Aim2-/- mice exhibit lower locomotor activity, increased anxious behaviors and reduced auditory fear memory. In conclusion, our study suggests that AIM2 inflammasomes regulate neuronal morphology and influence mouse behaviors. PMID- 27561457 TI - Comparative evaluation of the sexual functions and NF-kappaB and Nrf2 pathways of some aphrodisiac herbal extracts in male rats. AB - BACKGROUND: Mucuna pruriens, Tribulus terrestris and Ashwagandha (Withania somnifera) are widely known as antioxidant effective herbals and have been reported to possess aphrodisiac activities in traditional usages. In this study, we determined the effects of these herbals on sexual functions, serum biochemical parameters, oxidative stress and levels of NF-kappaB, Nrf2, and HO-1 in reproductive tissues. METHODS: Thirty-five male rats were divided into five groups: the control group, sildenafil-treated group (5 mg/kg/d), Mucuna, Tribulus and Ashwagandha groups. The extract groups were treated orally either with Mucuna, Tribulus or Ashwagandha (300 mg/kg b.w.) for 8 weeks. RESULTS: All of the extracts were found to be significantly effective in sexual functioning and antioxidant capacity and Tribulus showed the highest effectiveness. Serum testosterone levels significantly increased in Tribulus and Ashwagandha groups in comparison to control group. Tribulus was able to reduce the levels of NF-kappaB and increase the levels of Nrf2 and HO-1 to a much greater extent than Mucuna and Ashwagandha. CONCLUSIONS: These results demonstrate for the first time that Mucuna, Tribulus and Ashwagandha supplementation improves sexual function in male rats via activating Nrf2/ HO-1 pathway while inhibiting the NF-kappaB levels. Moreover, Tribulus terrestris extract was found to be more bioavailable from Ashwagandha extract followed by Mucuna extract. Schematic representation of the mode of action of some aphrodisiac herbal extracts to improve sexual functions. PMID- 27561458 TI - After phrenology: Time for a paradigm shift in cognitive science. AB - Anderson (2014) uses an impressive, consolidating review of the literature to argue for major changes in cognitive science. Arguably, however, much of what he proposes is not particularly new. He also neglects important predictive coding approaches that call his perspective of the brain into question, and his misconstrual of evolutionary psychology devalues an influential paradigm that promises to complement his own. PMID- 27561459 TI - Plexiform angiomyxoid myofibroblastic tumor of the stomach: A case report. AB - Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare mesenchymal tumor of the stomach. To date, about 40 cases of PAMT have been reported in the literature. This tumor is not specific in clinical manifestations and microscopically characterized by a plexiform growth pattern. Here, we report the case of an 11-year-old male patient who was diagnosed with PAMT. He had a complaint of right epigastric discomfort with episodic pain, gastroscopy displayed a submucosal bulge at the pylorus, and CT showed a mass in the right abdomen with uneven, delayed enhancement, and a partial gastrectomy revealed a tumor at the pylorus. Histologically, the tumor was multinodular and rich in blood vessels with thin wall; the interstitium had abundant myxomatous stroma; the tumor cells were spindle-shaped, star-shaped, or oval. Immunohistochemically, the tumor cells were positive for Calponin, Caldesmon, and SMA, but negative for CD34, ALK, S-100, desmin, CD117, and Dog-1. This patient was followed up for 12 months, and recurrence or metastasis was not observed. Diagn. Cytopathol. 2017;45:55-58. (c) 2016 Wiley Periodicals, Inc. PMID- 27561460 TI - Ultrasociality without group selection: Possible, reasonable, and likely. AB - It is uncontroversial that humans are extremely social, and that cultures have changed over time. But, the evidence shows that much of the social psychology underlying these phenomena (1) predates the agricultural transition, and (2) is not the result of group selection. Instead, this psychology appears intricately designed to capture social gains when possible in our complex ancestral social ecology. PMID- 27561461 TI - Morphology Engineering of Co3O4 Nanoarrays as Free-Standing Catalysts for Lithium Oxygen Batteries. AB - The effective shape-controlled synthesis of Co3O4 nanoarrays on nickel foam substrates has been achieved through a simple hydrothermal strategy. When they served as the binder- and conductive-agent-free porous cathodes for nonaqueous Li O2 batteries, they sufficiently reflect the favorable catalytic characteristic of Co3O4 and alleviate the problems of serious pore blocking and surface passivation caused by insoluble and insulating discharge products. In particular, Co3O4 rectangular nanosheets exhibit superior electrocatalytic performance comparing with Co3O4 nanowires and hexagonal nanosheets, leading to higher specific capacity and better cycling stability over 54 cycles at 100 mA g(-1), which relate to their good pore structure, large specific surface area, and highly active {112} exposed plane, effectively promoting the mass transport and reversible formation and decomposition of discharge products in the cathode. These comparisons further indicate the morphology effect of nanostructured Co3O4 on their performances as free-standing catalysts for Li-O2 batteries, which also have been proved through the further analysis of discharge products on different shapes of Co3O4 nanoarrays electrodes. PMID- 27561462 TI - Identification of Staphylococcus argenteus in Eastern China based on a nonribosomal peptide synthetase (NRPS) gene. AB - AIM: To investigate whether the Staphylococcus argenteus is present in Eastern China and to verify the utility of a new screening process. MATERIALS & METHODS: Phenotype observation, PCR assay targeting a hypothetical nonribosomal peptide synthetase (NRPS) gene, phylogenetic analysis of rpoB and multilocus sequence typing were used to screen and identify strains of S. argenteus from 839 presumptive S. aureus isolates. RESULTS: Eighty-nine (89/839, 10.6%) of the presumptive S. aureus isolates produced white colonies on tryptone soya agar plates. Of the white-colony isolates, six (6/89, 7%) were S. argenteus, 75 (75/89, 84%) were S. aureus and eight (8/89, 9%) were other bacteria. CONCLUSION: The PCR-based method targeting the NRPS gene can simultaneously identify and distinguish S. argenteus and S. aureus. All representative sequences of rpoB generated in this study were deposited in GenBank under accession numbers SJTU F20002, KT767581; SJTU F20269, KT767582; SJTU F20419, KT767583; SJTU F20420, KT767584; SJTU F20124, KT767585; SJTU F21164, KT767586; SJTU F21285, KT767587; SJTU F21224, KT767588; SJTU F21155, KT767589; SJTU F21294, KT767590; SJTU F20030, KT767591; SJTU F20044, KT767592; SJTU F20135, KT767593; SJTU F20123, KT767594; SJTU F21319, KT767595, respectively. All the new sequence types (STs) were submitted to a multilocus sequence typing database and the assigned ST numbers are ST3261 (151-469-20-101-145-150-131), ST3262 (12-3-1-1-4-4-410) and ST3267 (2 471-2-2-6-3-2). PMID- 27561463 TI - Safety of drug treatments for head and neck cancer. AB - INTRODUCTION: The treatment of squamous cell carcinoma of the head and the neck depends on the disease's stage. In locally-advanced stage disease, multimodal treatment strategies, including surgery, radiotherapy and chemotherapy, give the best outcome in terms of overall survival. Those treatments are not without negligeable adverse events, which can lead to late debilitating toxicities. In recurrent/metastatic disease, not amenable to surgery or radiation therapy, palliative chemotherapy is the most appropriate treatment. Areas covered: This review aims to provide an overview of the safety of standard drug regimens used to treat SCCHN in daily practice, including platinum-based chemoradiation, induction chemotherapy, cetuximab and immunotherapy. The toxicities induced by single modality radiotherapy, or those resulting from surgery, are not part of the discussion. Expert opinion: Toxicities observed with multimodal treatment of SCCHN are the highest we can tolerate in terms of treatment-related mortality, morbidity and late consequences. Patients at high risk of developing such complications should be identified upfront for optimal prevention and management. There is a medical need to identify less toxic regimens without compromising the treatment efficacy, especially for patients with Human Papilloma Virus-induced oropharyngeal cancers. Finally, it is crucial in future trials to better standardize the scales used to report treatment related adverse events. PMID- 27561464 TI - Undernutrition in the parental and first generation provokes an organ-specific response to oxidative stress on neonates of second filial generation of Wistar rats. AB - Undernutrition induces an increase of the oxidative stress that can predispose offspring to various diseases in adulthood through epigenetic reprogramming. The aim of this study was to evaluate the effects of intergenerational undernutrition on protein oxidation and antioxidant defence response on liver, heart and brain of the second-generation neonates (F2 ) of undernourished rats. For this purpose, both parents in parental (F0 ) and first generation (F1 ) were fed with a low nutrient diet. Body mass and length decreased (p < 0.05) in F0 , F1 and F2 being the F1 males who exhibited a greater mass loss. A decrease in plasma albumin concentration was observed in F2 neonates (p < 0.05) and also a mass loss of liver, heart and brain (p < 0.05), although proportionally to body length reduction. Undernutrition increased levels of protein oxidation in liver and heart (p < 0.05) but not in brain (p > 0.05) while catalase activity increased only in brain (p < 0.05). In summary, intergenerational undernutrition modifies the antioxidant status through an organ-specific response, on F2 neonate rats, where the brain increased catalase activity to prevent a severe oxidative damage and support the vital functions of this key organ to maintain vital functions. PMID- 27561465 TI - CO2-responsive aliphatic tertiary amine-modified alginate and its application as a switchable surfactant. AB - A new kind of hexyl diethyl tertiary amine-grafted amphiphilic alginate derivative (HDEA-Alg) was synthesized from (6-bromo-hexyl)-diethyl-amine (BHDEA) and sodium alginate (NaAlg) through esterification. The structure of HDEA-Alg was confirmed by FT-IR and NMR spectroscopies. The grafting ratio was calculated according elemental analysis and thermodynamic property was analyzed by TG. The CO2/N2-responsive performance of HDEA-Alg in aqueous solution was demonstrated by surface tension and conductivity measurements. Stable emulsions of liquid paraffin were easily prepared in the presence of the HDEA-Alg. These emulsions can be de-emulsified by bubbling CO2 through the emulsions at 5 degrees C for 30min, resulting in complete oil/water phase separations. They can be re emulsified by bubbling N2 through the solutions at 50 degrees C for 30min with the aid of homogenization. PMID- 27561466 TI - Structural modification of hemicelluloses and lignin based on the biorefinery process with white-rot fungal. AB - On the concept of biorefinery, hemicellulosic and lignin fractions were isolated from white-rot fungal Trametes velutina D10149 biodegraded poplar, and the structural modification was elucidated in detail according to the different incubation duration. Transversal-section Raman images showed that the fiber secondary walls were preferentially degraded, whereas the compound middle lamellae, including the cell corner regions, were mainly intact after 16 weeks incubation. More importantly, lignin and carbohydrates were simultaneously removed within the fiber secondary wall. From wet chemistry analysis, the yields and structural properties for both hemicellulosic and lignin fractions were not significantly altered. The synergistic effect of ligninolytic system finally obviously appeared after 16 weeks incubation, evidenced by the remarkable decrement of hemicellulose and lignin molecular weights. Additionally, the preferential degradation of S units in lignin biomacromolecule was further confirmed by composition analysis of cell wall phenolics and the integration of 2D NMR correlations in the aromatic region. PMID- 27561467 TI - Protein-free cress seed (Lepidium sativum) gum: Physicochemical characterization and rheological properties. AB - Protein-free cress seed gum (PFCSG) was obtained by precipitation of crude cress seed gum (CSG) with ethanol followed by treatment with protease. Molecular weight, moisture, ash and uronic acids content decreased after elimination of protein. Elimination of protein improved significantly rheological properties and thermal stability of cress seed gum. Mechanical spectra of the CSG and PFCSG were classified as weak gels and PFCSG showed stronger and more elastic network structure. The gum dispersions exhibited strong shear-thinning behavior which was described satisfactory by the Herschel-Bulkley and Moore models. Protein-free cress seed gum had higher apparent and intrinsic viscosities than the crude gum. CSG indicated lower hysteresis loop area, but degree of structural recovery of the samples showed no significant difference. The main decomposition of PFCSG started above 213 degrees C with two peaks (at 261.72 degrees C and 306.58 degrees C) and initial decomposition temperature of CSG was 190.21 degrees C with one peak at 258.28 degrees C. DSC results coincided with those observed by thermogravimetric analysis. Enzyme treatment lowered the surface activity of CSG. PMID- 27561468 TI - Characterization and sulfated modification of an exopolysaccharide from Lactobacillus plantarum ZDY2013 and its biological activities. AB - An exopolysaccharide (EPS) from probiotics Lactobacillus plantarum ZDY2013 was purified to illustrate its molecular weight, monosaccharide composition and biological activities. The yield of EPS (429.4+/-30.3mg/L) was obtained with a purity of 96.06%. The EPS was characterized to have only one symmetrical sharp peak by high-performance size-exclusion chromatography and its molecular weight was 5.17*10(4)Da. The GC analysis revealed that EPS only consisted of xylose and galactose, and the galactose possessed as high as 98.3% (w/w) of the total monosaccharides. By sulfonation, a sulfated EPS was successfully synthesized with the degree of substitution (DS) of 0.29, which was confirmed using FT-IR spectroscopy. Both EPS and sulfated EPS showed radical scavenging activities, and the antioxidant activities increased after sulfonation. In addition, sulfated EPS was more effective in counteracting the cytotoxicity induced by B. cereus enterotoxins on Caco-2 cells when compared with EPS. In summary, sulfonation is a feasible strategy for improving the biological activities of EPS from L. plantarum ZDY203. PMID- 27561469 TI - Development of a sodium alginate-based organic/inorganic superabsorbent composite hydrogel for adsorption of methylene blue. AB - Batch adsorption experiments were carried out for the removal of methylene blue (MB) cationic dye from aqueous solution using organic/inorganic hydrogel nanocomposite of titania incorporated sodium alginate crosslinked polyacrylic acid (SA-cl-poly(AA)-TiO2). The hydrogel was prepared by graft copolymerization of acrylic acid (AA) onto sodium alginate (SA) biopolymer in the presence of a crosslinking agent, a free radical initiator and TiO2 nanoparticles. The hydrogel exhibited a high swelling capacity of 412.98g/g. The factors influencing adsorption capacity of the absorbents such as pH of the dye solutions, initial concentration of the dye, amount of absorbents, and temperature were investigated and used to propose a possible mechanism of adsorption. The adsorption process concurs with a pseudo-second-order kinetics and with Langmuir isotherm equation. A very high adsorption capacity (Qmax=2257.36 (mg/g)) and a correlation coefficient of 0.998 calculated from isotherm equations show the high efficiency of the absorbent and thus expected to be a good candidate as an absorbent for water treatment. PMID- 27561470 TI - Qualitation and quantification of specific polysaccharides from Panax species using GC-MS, saccharide mapping and HPSEC-RID-MALLS. AB - The objective of this study was to qualify and quantify the specific polysaccharides in Panax spp. The analyses of specific polysaccharides were performed by using GC-MS, saccharide mapping and high performance size exclusion chromatography (HPSEC) coupled with multi angle laser light scattering (MALLS) and refractive index detector (RID). Results showed that compositional monosaccharides were the same in different species of Panax and composed of rhamnose, arabinose, galacturonic acid, mannose, glucose, and galactose. Saccharide mapping results showed that glycosides linkages, which existed in specific polysaccharides from Panax spp., were similar. Additionally, the content of specific polysaccharides of P. ginseng, P. notoginseng and P. quinquefolium were 17.9-20.5mg/g, 11.9-15.0mg/g, and 9.9-13.3mg/g, respectively. P. ginseng, P. notoginseng, and P. quinquefolium could be clustered into three groups using both hierarchical cluster analysis and principal component analysis. The results possessed great potential in characterization and content determination of specific polysaccharides in Panax spp. PMID- 27561471 TI - Preparation of chitin nanofibers by surface esterification of chitin with maleic anhydride and mechanical treatment. AB - Esterification with maleic anhydride significantly improved the mechanical disintegration of chitin into uniform 10-nm nanofibers. Nanofibers with 0.25 degrees of esterification were homogeneously dispersed in basic water due to the carboxylate salt on the surface. Esterification proceeded on the surface and did not affect the relative crystallinity. A cast film of the esterified chitin nanofibers was highly transparent, since the film was free from light scattering. PMID- 27561472 TI - Synthesis, characterization and antimicrobial applications of zinc oxide nanoparticles loaded gum acacia/poly(SA) hydrogels. AB - In this work, zinc oxide nanoparticles were synthesized in-situ within the gum acacia/poly (acrylate) hydrogel network using hydrothermal approach. The synthesized zinc oxide nanoparticles were characterized by Surface plasmon resonance (SPR), X-Ray diffraction (XRD) analysis, Fourier transform infrared (FTIR) spectroscopy and Scanning electron microscopy (SEM). The water absorption behavior of ZnO/GA/poly(SA) hydrogels was investigated in the phosphate buffer saline (PBS) of pH 7.4 at 37 degrees C. The water uptake data were analyzed with the help of various kinetic models. Finally, the antimicrobial action of nanocomposites was studied using E. coli as model bacteria. PMID- 27561473 TI - Structural characteristics of oxalate-soluble polysaccharides of Sosnowsky's hogweed (Heracleum sosnowskyi Manden). AB - Arabinogalactan proteins (AGP) and pectic polysaccharides were isolated from above-ground parts of Heracleum sosnowskyi. The structural study has shown that a linear region of the pectic macromolecules consists of 1,4-alpha-d galactopyranosyluronan blocks partially methyl esterified and acetylated. The branched region consists of 3-O- and partially 2-O-acetylated rhamnogalacturonan I. Side chains of the RG-I backbone include the regions of arabinogalactan I and branched 1,5-alpha-l-arabinan. The carbohydrate part of AGP consists of arabinogalactan II with a 1,3-beta-d-Galp main chain. The side chains of the branched area of AG-II are composed of 1,6-beta-d-Galp, 1,5-, 1,3,5-alpha-l-Araf, 4-O-Me-beta-d-GlcA and 1,4-beta-d-GlcpA, and non-reducing ends residues of beta-d Galp, alpha-l-Araf, alpha-l-Rhap and alpha-l-Fucp. The branch points of the main and side chains are formed by 3,6-di-O-substituted beta-d-Galp. It was found that at least a portion of pectin is probably covalently linked to AGP, wherein AGP is linked to RG-I, but not with galacturonan. PMID- 27561474 TI - Citric acid based durable and sustainable flame retardant treatment for lyocell fabric. AB - Pyrovatex CP New, is a commonly used organophosphorus based flame retardant (FR) reagent for cellulosic materials. However, it has a drawback of high formaldehyde release when used with methylated melamine (MM) based cross-linker, a known carcinogenous compound. In the present approach, a durable and sustainable flame retarding recipe formulation for lyocell fabrics is developed using citric acid (CA) as a cross-linker. The FR finish was applied by pad-dry-cure process. The treated fabrics were characterized for surface morphology, elemental analysis, TG analysis, char study and FT-IR spectroscopy. Furthermore, flame retardancy, washing durability, formaldehyde release and breaking strength were also assessed, and compared with the conventional MM based FR recipe. The fabric samples treated with 400gL(-1) of FR with either 40 or 80gL(-1) of CA demonstrate flame retardancy even after 10 washing cycles. Furthermore, a 75% reduction in formaldehyde release is achieved. Higher char yield and lower decomposition temperature are found compared to untreated and FR+ MM treated lyocell. Such an improved sustainable recipe formulation can be used for lyocell fabric without any health risk in apparel wear. PMID- 27561475 TI - Reactive blending of thermoplastic starch and polyethylene-graft-maleic anhydride with chitosan as compatibilizer. AB - Cassava starch was melt-blended with glycerol (70/30wt%/wt%) at 140 degrees C to prepare thermoplastic starch (TPS). Chitosan (CTS) was premixed with starch and glycerol, in acidified water (lactic acid 2wt%), at 1, 5 and 10wt%/wt%. TPS/CTS was then melt-blended (160 degrees C) with polyethylene-graft-maleic anhydride (PE-MAH). Phase determination and scanning electron microscopy indicated TPS/PE MAH/CTS had a co-continuous morphology and CTS-induced phase inversion to give dispersed PE-MAH particles in a TPS matrix. Tensile strength at break and elongation, melt viscosity, fracture toughness and water contact angle of TPS/PE MAH were improved by CTS incorporation. TPS/PE-MAH/CTS blends decreased the melting temperature of TPS and PE-MAH compared to the neat polymers. FTIR confirmed a reaction had occurred between amino groups (NH2) of CTS and the MAH groups of PE-MAH. This reaction and the enhanced miscibility between TPS and CTS improved the mechanical properties of the TPS/PE-MAH/CTS blend, particularly at 5wt%/wt% CTS. PMID- 27561476 TI - Synthesis of multivalent sialyllactosamine-carrying glyco-nanoparticles with high affinity to the human influenza virus hemagglutinin. AB - A series of multivalent sialoglyco-conjugated nanoparticles were efficiently synthesized by using highly-branched alpha-glucuronic acid-linked cyclic dextrins (GlcA-HBCD) as a backbone. The sialoglycoside-moieties, with varying degrees of substitution, could be incorporated onto the preformed nanoparticles. These synthesized particles, which are highly soluble in aqueous solution, were shown to have a spherical nanostructure with a diameter of approximately 15nm. The interactions of the sialoglyco-nanoparticles (Neu5Acalpha2,6LacNAc-GlcA-HBCDs) with human influenza virus strain A/Beijing/262/95 (H1N1) were investigated using a hemagglutination inhibition assay. The sialoglyco-nanoparticle, in which the number of sialic acid substitution is 30, acted as a powerful inhibitor of virus binding activity. We show that both distance and multiplicity of effective ligand virus formation play important roles in enhancing viral inhibition. Our results indicate that the GlcA-HBCD backbone can be used as a novel spherical nanocluster material for preparing a variety of glyco-nanoparticles to facilitate molecular recognition. PMID- 27561478 TI - Development of a novel cellulose/duck feather composite fibre regenerated in ionic liquid. AB - By blending cellulose and duck feather in the common solvent 1-allyl-3 methylimidazoloium chloride, a regenerated composite fibre has been developed with improved fibres over regenerated cellulose fibres (RCF). The mechanical properties of composite fibre was shown to be better than RCF with a 63.7% improvement in tensile strain. Here, we thoroughly characterise the composite fibre and show that the composite fibre has many advantages over RCFs both from a spinning perspective and as a regenerated fibre. PMID- 27561477 TI - Transglutaminase catalyzed hydrolyzed wheat gliadin grafted with chitosan oligosaccharide and its characterization. AB - Chitosan oligosaccharide (COS) was grafted on hydrolyzed wheat gliadin (HWG) with microbial transglutaminase (MTGase) as catalyst. The grafting reaction exhibited the best performance when it was done under the optimum temperature 50 degrees C for 50min with HWG/COS mass ratio of 40:1, pH 6.00-6.50. The maximum grafting rate of COS was 64.83% at this condition. The chemical structure characterizations of HWG-COS performed by FTIR, (13)C NMR, X-ray diffractometry and TGA-DTG illustrated that amino groups in COS had participated in the formations of the amino band during the synthesis. HPLC and GFC analysis showed that HWG-COS had two main components, which together accounted for 80.64% of the total polymer and the molecular weight of the two components was 61.77kDa and 27.29kDa, respectively. HWG-COS was undissolved in water and many organic solvent, slightly soluble in 1% NaOH, with a solubility of 1.84mg/L. In antibacterial activity test, HWG-COS showed the best antimicrobial properties to Salmonella enteriditis, with an antibacterial activity improved by 41.74%. PMID- 27561479 TI - A novel porous aspirin-loaded (GO/CTS-HA)n nanocomposite films: Synthesis and multifunction for bone tissue engineering. AB - A novel porous graphene oxide (GO)/chitosan (CTS)-hydroxyapatite (HA) nanocomposite film was successfully prepared for the first time by combining layer-by-layer (LBL) assembly technology with biomimetic mineralization method. The LBL technology was used to control the thickness of film as well as induce the biomimetic mineralization of biocompatible HA. The obtained (GO/CTS-HA)n film provided ideal platform for the proliferation of mouse mesenchymal stem cells (mMSCs). The pore size in the film is about 300nm, and the porous architecture made the film have high aspirin loading efficiency. Also the accumulated loading dosage could be adjusted by the film thickness, and the sustained release of aspirin could ensure well anti-inflammatory effect. The above advantages may alleviate the pain of patients and give the better environment for bone regeneration. This multifunctional aspirin-loaded (GO/CTS-HA)n film provided an inspiration for the synthesis of novel porous inorganic/biomacromolecule nanocomposite films as the biocoatings applied in bone tissue engineering. PMID- 27561480 TI - Cashew gum and inulin: New alternative for ginger essential oil microencapsulation. AB - This study aimed to evaluate the effect of partial replacement of cashew gum by inulin used as wall materials, on the characteristics of ginger essential oil microencapsulated by spray drying with ultrasound assisted emulsions. The characterization of particles was evaluated as encapsulation efficiency and particle size. In addition, the properties of the microcapsules were studied through FTIR analysis, adsorption isotherms, thermal gravimetric analysis, X-ray and scanning electron microscopy. It was found that the solubility of the treatments was affected by the composition of the wall material and reached higher values (89.80%) when higher inulin concentrations were applied. The encapsulation efficiency (15.8%) was lower at the highest inulin concentration. The particles presented amorphous characteristics and treatment with cashew gum as encapsulant exhibited the highest water absorption at high water activity. The cashew gum and inulin matrix (3:1(w/w) ratio) showed the best characteristics regarding the encapsulation efficiency and morphology, showing no cracks in the structure. PMID- 27561481 TI - Mechanical properties of natural rubber nanocomposites reinforced with high aspect ratio cellulose nanocrystals isolated from soy hulls. AB - Cellulose nanocrystals (CNCs) were isolated from soy hulls by acid sulfuric hydrolysis. The resulting CNCs were characterized using TEM, AFM, WAXS, elemental analysis and TGA. The CNCs have a high crystallinity, specific surface area and aspect ratio. The aspect ratio (around 100) is the largest ever reported in the literature for a plant cellulose source. These CNCs were used as a reinforcing phase to prepare nanocomposite films by casting/evaporation using natural rubber as matrix. The mechanical properties were studied in both the linear and non linear ranges. The reinforcing effect was higher than the one observed for CNCs extracted from other sources. It may be assigned not only to the high aspect ratio of these CNCs but also to the stiffness of the percolating nanoparticle network formed within the polymer matrix. Moreover, the sedimentation of CNCs during the evaporation step was found to play a crucial role on the mechanical properties. PMID- 27561482 TI - Characterization of whey protein-carboxymethylated chitosan composite films with and without transglutaminase treatment. AB - Edible composite packaging has the advantage of complementary functional properties over its each bio-components. However, reports on whey protein concentrates (WPC)-carboxymethylated chitosan (CMC) composite films have not yet been released. To investigate the preparation of WPC-CMC composite films and its functional properties, four types of WPC-CMC composite films were prepared with and without Transglutaminase (TGase) treatment by mixing WPC aqueous solutions (10%, w/v) with CMC aqueous solutions (3%, w/v) at WPC to CMC volume ratios of (100:0), (75:25), (50:50), and (25:75). SDS-PAGE confirmed that TGase catalyzed crosslinking of whey protein. Results revealed that CMC incorporation conferred a smooth and even surface microstructure on the films and markedly improved the transparency, water barrier properties, mechanical properties and solubility of the composite film. Furthermore, TGase resulted in an improvement in the water vapor barrier properties and mechanical properties of WPC-CMC (75:25 and 50:50, v/v) composite films, and there was no impairment of thermal stability of composite films. Therefore, TGase successfully facilitated the formation of WPC CMC composite films with some improved functional properties. This offers potential applications as an alternative approach to the preparation of edible packaging films. PMID- 27561483 TI - Bioreducible PEI-functionalized glycol chitosan: A novel gene vector with reduced cytotoxicity and improved transfection efficiency. AB - Non-viral gene delivery has been well recognised as a potential way to address the main safety limitations of viral gene carriers. A new redox-responsive PEI derivative was designed, synthesized and evaluated for non-viral delivery applications of GFP DNA. Glycol chitosan was covalently attached to highly branched LMW PEI via bio-cleavable disulfide bonds to synthesize a new redox responsive gene carrier (GCS-ss-PEI). Results showed the enhanced buffering capacity of GCS-ss-PEI, 43.1%, compared to the buffering capacities of both LMW PEI and HMW PEI, 23.2% and 31.5%, respectively, indicating more likely endosomal escape of the entrapped gene for GCS-ss-PEI. Moreover, electrophoretic gel retardation assay, performed to investigate the binding strength of GCS-ss-PEI to GFP DNA, showed stronger complexation with GFP DNA in GCS-ss-PEI at non-GSH condition. Employing GCS and incorporation of disulfide bonds in the structure of the PEI-based gene carrier resulted in improved redox-responsivity, reduced toxicity, enhanced endosomal escape and GFP DNA transfection. The facilitated intracellular gene release along with excellent redox-responsive characteristics and dropped cytotoxicity suggests the potential of GCS-ss-PEI as a candidate for developing highly efficient and safe gene vectors. PMID- 27561484 TI - Chitosan-coated microvesicles: Effect of polysaccharide-phospholipid affinity on decafluorobutane dissolution. AB - The stability of perfluorinated microvesicles is mainly determined by the presence of interfacial materials and their ability to hinder the gas component diffusibility into the bloodstream. The goal of this study is to increase the persistence of the gaseous-core by introducing chitosan-coated 1,2-distearoyl-sn glycero-3-phosphocholine (DSPC) microvesicles, reducing gas diffusion from microvesicles, and increasing for a long time ultrasonic signals. Our hypothesis was based on the irreversible adhesion of chitosan towards DSPC head groups observed in thin-films models. This affinity enhanced the stabilization of gaseous-core microvesicles, in which the polysaccharide effectively reduced the phospholipid phase transition enthalpy from 383+/-5.5Jmg(-1) for plain to 150+/ 9.7Jmg(-1) for chitosan-coated microvesicles, providing a more stable structure that diminished the gaseous component lost and provided the persistence of intense (19)F-NMR signals after 48h, twice as long compared to plain samples. As a result, stronger and long-lasting ultrasonic signals were produced by the more stable chitosan-containing microvesicles, thus, presenting great potential to increase the diagnostic and therapeutic applications of perfluorocarbon carries. PMID- 27561485 TI - Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel. AB - This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above +/-30mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl. PMID- 27561486 TI - Polysaccharides purified from Cordyceps cicadae protects PC12 cells against glutamate-induced oxidative damage. AB - Two polysaccharides CPA-1 and CPB-2 were isolated purified from Cordyceps cicadae by hot water extraction, ethanol precipitation and purification using anion exchange and gel filtration chromatography. Preliminary structural characterization of CPA-1 and CPB-2 were performed. The protective effect of CPA 1 and CPB-2 against glutamate-induced oxidative toxicity in PC12 cells was analyzed. The results indicated that pretreatment of PC12 cells with CPA-1 and CPB-2 significantly increased cell survival, Ca(2+) overload and ROS generation. CPA-1 and CPB-2 also markedly up-regulated the antioxidant status of pretreated PC12 cells. Our results suggested that Cordyceps cicadae polysaccharides can protect PC12 cells against glutamate excitotoxicity and might serve as therapeutic agents for neuronal disorders. PMID- 27561487 TI - Scattering investigation of multiscale organization in aqueous solutions of native xanthan. AB - The hierarchical morphology of xanthan solutions is analyzed by light and neutron scattering in a broad range of concentrations in order to connect their morphology to their well-documented dynamic properties. Static light scattering inside the semidilute regime is dominated by the form factor of individual xanthan chains while at higher concentrations chain interconnections appear to modify the low wave vector scattering. Dynamic light scattering reveals the self similar nature of the solutions caused by interchain associations as intensity autocorrelation functions present power-law behaviour. Small angle neutron scattering is dominated by the fractal scattering from the formed network at intermediate length scales. At small length scales the rigid structure of xanthan is revealed and the molecular weight per unit length is extracted. No detectable morphological alterations for shear rates up to 1000rad/s are observed revealing that the shear thinning behaviour of xanthan is related to the disruption of chain-chain associations. PMID- 27561488 TI - Synthesis, characterization and drug release properties of 3D chitosan/clinoptilolite biocomposite cryogels. AB - Three-dimensional (3D) biocomposites based on chitosan (CS) and clinoptilolite (CPL) were prepared by cryogelation and their potential application as drug carriers was investigated. Variation of CPL content from 0 to 33wt.% allowed the formation of biocomposites with heterogeneous morphologies consisting of randomly distributed pores. The further increase of CPL content led to ordered porous architectures where parallel pore channels were observed. The CPL content had a strong influence on water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2), where only a reduced drug release was observed. The drug release mechanism dominating these systems is described as a pseudo-Fickian diffusion, but it changes to non-Fickian release when 33wt.% of CPL was entrapped into the CS matrix or when IDM was loaded into biocomposites. PMID- 27561489 TI - Towards the development of multifunctional chitosan-based iron oxide nanoparticles: Optimization and modelling of doxorubicin release. AB - In the present work composite nanoparticles with a magnetic core and a chitosan based shell were produced as drug delivery systems for doxorubicin (DOX). The results show that composite nanoparticles with a hydrodynamic diameter within the nanometric range are able to encapsulate more DOX than polymeric nanoparticles alone corresponding also to a higher drug release. Moreover the synthesis method of the iron oxide nanoparticles influences the total amount of DOX released and a high content of iron oxide nanoparticles inhibits DOX release. The modelling of the experimental results revealed a release mechanism dominated by Fickian diffusion. PMID- 27561491 TI - Study of drying process on starch structural properties and their effect on semolina pasta sensory quality. AB - The influence of drying temperature on the starch crystallites and its impact on durum wheat pasta sensory properties is addressed in this work. In particular, spaghetti were produced by means of a pilot plant using 5 different drying temperature profiles. The sensory properties, as well as the cooking quality of pasta were assessed. X-ray powder diffraction was used for investigating changes in the crystallinity content of the samples. Starch crystallinity, size and density of the starch crystallites were determined from the analysis of the diffraction profiles. As expected, spaghetti sensory properties improved as the drying temperatures increased. In particular, attributes as resistance to break for uncooked samples and firmness, elasticity, bulkiness and stickiness for cooked samples, all benefit from drying temperature increase. The spaghetti cooking quality was also positively affected by the drying temperature increase. Diffraction analysis suggested that the improvement of sensory properties and cooking quality of pasta were directly related to the increase in density of both physical crosslink of starch granules and chemical crosslink of protein matrix. PMID- 27561490 TI - Polyamines as new cationic plasticizers for pectin-based edible films. AB - Zeta potential and particle size were determined on pectin aqueous solutions as a function of pH and the effects of calcium ions, putrescine and spermidine on pectin film forming solutions and derived films were studied. Ca(2+) and polyamines were found to differently influence pectin zeta potential as well as thickness and mechanical and barrier properties of pectin films prepared at pH 7.5 either in the presence or absence of the plasticizer glycerol. In particular, Ca(2+) was found to increase film tensile strength and elongation at break only in the presence of glycerol and did not affect film thickness and permeability to both water vapor and CO2. Conversely, increasing polyamine concentrations progressively reduced film tensile strength and markedly enhanced film thickness, elongation at break and permeability to water vapor and CO2, both in the presence and absence of glycerol. Our findings indicate that polyamines give rise to a structural organization of the heteropolysaccharide different from that determined by calcium ions, previously described as "egg box" model, and suggest their possible application as plasticizers to produce pectin-based "bioplastics" with different features. PMID- 27561492 TI - Pectin impacts cellulose fibre architecture and hydrogel mechanics in the absence of calcium. AB - Pectin is a major polysaccharide in many plant cell walls and recent advances indicate that its role in wall mechanics is more important than previously thought. In this work cellulose hydrogels were synthesised in pectin solutions, as a biomimetic tool to investigate the influence of pectin on cellulose assembly and hydrogel mechanical properties. Most of the pectin (60-80%) did not interact at the molecular level with cellulose, as judged by small angle scattering techniques (SAXS and SANS). Despite the lack of strong interactions with cellulose, this pectin fraction impacted the mechanical properties of the hydrogels through poroelastic effects. The other 20-40% of pectin (containing neutral sugar sidechains) was able to interact intimately with cellulose microfibrils at the point of assembly. These results support the need to revise the role of pectin in cell wall architecture and mechanics, and; furthermore they assist the design of cellulose-based products through controlling the viscoelasticity of the fluid phase. PMID- 27561493 TI - Synthesis and characterization of poly(maleic acid)-grafted crosslinked chitosan nanomaterial with high uptake and selectivity for Hg(II) sorption. AB - Chitosan-poly(maleic acid) nanomaterial (PMACS) with the size of 400-900nm was synthesized by grafting poly(maleic acid) onto chitosan and then crosslinking with glutaraldehyde. The synthesis conditions were optimized. The structure and morphology of PMACS were characterized by FT-IR, XRD, SEM and TGA. PMACS was used to adsorb some heavy metal ions such as Hg(II), Pb(II), Cu(II), Cd(II), Co(II), and Zn(II). The results indicated that PMACS had selectivity for Hg(II) sorption. The effects of various variables for sorption of Hg(II) were further explored. The maximum capacity for Hg(II) sorption was found to be 1044mgg(-1) at pH 6.0, which could compare with the maximal value of the recently reported other sorbents. The sorption followed the pseudo-second-order kinetics and Langmuir isotherm models. The rising of temperature benefited the uptake and the sorption was a spontaneous chemical process. The sorbent could be reused with EDTA. Hence, the nanomaterial would be used as a selective and high uptake sorbent in the removal of Hg(II) from effluents. PMID- 27561494 TI - Preparation of pure chitosan film using ternary solvents and its super absorbency. AB - Chemical modification and graft copolymerization were commonly adopted to prepare super absorbent materials. However, physical microstructure of pure chitosan film was optimized to improve the water uptake capacity in this study. Chitosan films with micro-nanostructure were prepared by a ternary solvent system. The optimal process parameters are 1% acetic acid water solution: dioxane: dimethyl sulfoxide=90: 2.5: 7.5 (v/v/v) with chitosan concentration at 1.25% (w/v). The water uptake capacity of the chitosan film prepared under the optimal process parameters was 896g/g. The prepared chitosan films also exhibited high water uptake capacity in response to external stimuli such as temperature, pH and salt. This finding may provide another way for improving the water absorbency. The pure chitosan film may find potential applications especially in the fields of hygienic products and biomedicine due to its super water absorbency and nontoxicity. PMID- 27561495 TI - The comparison of structure and anticancer activity in vitro of polysaccharides from brown algae Alaria marginata and A. angusta. AB - Laminaran and three fucoidan fractions were obtained from the brown alga Alaria marginata. Alaria angusta, studied earlier by us, has the same polysaccharide composition. Galactofucan AmF3 from A. marginata has a main chain of ->3)-alpha-l Fucp-(2,4-SO3(-))-(1->residues, similar to galactofucan from A. angusta. However, the structure of the branches in fucoidan AmF3 can differ from those in the fucoidan from A. angusta. The following fragments were identified in AmF3: HexA (1->2)-Fuc, HexA-(1->2)-Gal, Gal-(1->4)-HexA, Fuc-(1->2)-Gal-6-SO3(-), Fuc-4-SO3( )-(1->6)-Gal, Gal-(1->2)-Gal-2-SO3(-), Gal-4-SO3(-)-(1 ->6)-Gal, Gal-4-SO3(-)-(1 >3)-Fuc-(1->3)-Fuc, Fuc-4-SO3(-)-(1->6)-Gal-(1->4)-Gal, Gal-(1->4)-Gal-(1->3) Fuc, Gal-2-SO3(-)-(1->4)-Gal-(1->4)-Gal, Gal-(1->4)-Gal-6-SO3(-)-(1->2)-Gal. Chains of galactose residues (DP up to 9) were found in AmF3 fucoidan. The laminarans, galactofucans and their derivatives from both algae exhibited no cytotoxicity in vitro. Polysaccharides from A. angusta were more effective against colony formation of HT-29 cells, while those from A. marginata had a greater effect on T-47D cells. Sulfated and desulfated fucoidans possessed weak antitumor activity using SK-MEL-28 cells. PMID- 27561496 TI - Preparing hydrophobic nanocellulose-silica film by a facile one-pot method. AB - Hydrophobic nanocellulose-silica film was successfully prepared by a facile one pot method using tetraethoxysilane (TEOS) and dodecyl triethoxylsilane (DTES). Morphological characterization of the hydrophobic nanocellulose-silica (NC-SiO2 DTES) film showed well self-assembled DTES modified silica spherical nanoparticles with the particle sizes in the range of 88-126nm over the nanocellulose film. The hydrophobicity of the NC-SiO2-DTES film was achieved owing to the improvement of roughness of the nanocellulose film by coating dodecyl- terminated silica nanoparticles. An increase in DTES loading amount and reaction time increased the hydrophobicity of the film, and the optimum condition for NC-SiO2-DTES film preparation was achieved at DTES/TEOS molar ratio of 2.0 for 8h reaction time. Besides, the NC-SiO2-DTES film performed superoleophilic property with octane and hexadecane contact angles of 0 degrees . It also showed an excellent hydrophobic property over all pH values ranged from 1 to 14. PMID- 27561497 TI - Optimization of hyaluronan-based eye drop formulations. AB - Hyaluronan (HA) is frequently incorporated in eye drops to extend the pre-corneal residence time, due to its viscosifying and mucoadhesive properties. Hydrodynamic and rheological evaluations of commercial products are first accomplished revealing molecular weights varying from about 360 to about 1200kDa and viscosity values in the range 3.7-24.2mPa s. The latter suggest that most products could be optimized towards resistance to drainage from the ocular surface. Then, a study aiming to maximize the viscosity and mucoadhesiveness of HA-based preparations is performed. The effect of polymer chain length and concentration is investigated. For the whole range of molecular weights encountered in commercial products, the concentration maximizing performance is identified. Such concentration varies from 0.3 (wt%) for a 1100kDa HA up to 1.0 (wt%) for a 250kDa HA, which is 3-fold higher than the highest concentration on the market. The viscosity and mucoadhesion profiles of optimized formulations are superior than commercial products, especially under conditions simulating in vivo blinking. Thus longer retention on the corneal epithelium can be predicted. An enhanced capacity to protect corneal porcine epithelial cells from dehydration is also demonstrated in vitro. Overall, the results predict formulations with improved efficacy. PMID- 27561498 TI - Swelling and hydrolysis kinetics of Kraft pulp fibers in aqueous 1-butyl-3 methylimidazolium hydrogen sulfate solutions. AB - 1Butyl-3-methylimidazolium hydrogen sulfate ([Bmim]HSO4) is efficient at extracting cellulose nanocrystals from pulp fibers. To shed some light on the respective contributions of swelling and hydrolysis of pulp fibers by [Bmim]HSO4, the physical, structural and morphological characteristics of hardwood Kraft pulp fibers were monitored under various conditions of temperature, water content and time. Swelling was largely compounded by hydrolysis at the highest temperatures (120 degrees C) as evidenced by mass loss and reduced degree of polymerization (DPn) at this temperature. At 120 degrees C only, water content appeared to play a significant role on the extent of hydrolysis. At this temperature, a heterogeneous kinetic model involving weak links and amorphous regions best described the experimental data. Hydrolysis rates were maximum at 25% water content in the aqueous ionic liquid. PMID- 27561499 TI - Development of highly biocompatible Gelatin & i-Carrageenan based composite hydrogels: In depth physiochemical analysis for biomedical applications. AB - In present investigation, gelatin and iota-carrageenan (CG) were used for the fabrication of composite hydrogels in different formulations (G1-G6). The hydrogels were characterized through optical, scanning electron and confocal microscopy to visualize their internal morphology. X-ray diffraction and ATR- FTIR spectroscopy were used for analyzing the chemical interaction between gelatin and CG. The hydrogels were found to be hemocompatible with high mucoadhesive and swelling properties. The standard drug ciprofloxacin was incorporated within the hydrogels and its interaction with the polymers was monitored through XRD and ATR-FTIR spectroscopy. In physiological pH 7.4, the G4 formulation showed a linear release profile. The antimicrobial activity was tested against nosocomial strains of Bacillus sp, Vibrio sp, Pseudomonas sp and Escherichia coli which showed a zone of inhibition between 8.5-20.7mm against the marketed Ciplox ointment. The cytocompatibility of the prepared hydrogels were investigated using normal HaCaT and HEK293 cell lines which showed their negligible cytotoxicity. PMID- 27561500 TI - Selenylation modification can enhance immune-enhancing activity of Chuanminshen violaceum polysaccharide. AB - Chuanminshen violaceum polysaccharides (CVPS) were extracted, purified and selenizingly modified. The modification has been achieved by using the HNO3- Na2SeO3 method, and selenizing Chuanminshen violaceum polysaccharides (sCVPS) were evaluated for their physicochemical properties and their potential as adjuvant to modulate cellular and humoral immune responses to hepatitis B subunit vaccine in a mouse model. Our results demonstrated that sCVPS significantly promoted splenocytes proliferation and the production of IL-4 and IFN-gamma in vitro. In vivo experiments showed that sCVPS significantly increased the rHBsAg specific IgG level, IgG subclass (IgG1, IgG2a, and IgG2b) antibody titers, T cells proliferation, levels of IL-4, IL-2, and IFN-gamma in CD4 (+)T cells and the level of IFN-gamma in CD8(+)T cells. Furthermore, sCVPS increased the activity of natural killer cells and cytotoxic T lymphocytes, thus increasing both cellular and humoral immune responses in vivo. The present data suggest that selenylation of CVPS can significantly improve their immune-enhancing activity both in vitro and in vivo, thus representing a powerful adjuvant for vaccine design. PMID- 27561501 TI - Viscoelastic properties of aqueous guar gum derivative solutions under large amplitude oscillatory shear (LAOS). AB - The industrial relevant nonlinear viscoelastic properties of aqueous carboxymethyl hydroxypropyl guar gum (CMHPG) and non-ionic hydroxypropyl guar gum (HPG) solutions between semi-dilute and concentrated solution state were investigated by large amplitude oscillatory shear flow (LAOS). Aqueous CMHPG and HPG solutions enter the nonlinear flow regime at deformations gamma0>100%. The nonlinear stress waveforms were analyzed by FT-rheology and orthogonal stress decomposition along the MITlaos framework. A rheological fingerprint is generated (Pipkin space) showing that the guar gum derivative solutions undergo a shear thinning at high strains, which is preceded by a thickening above a minimum strain rate at intermediate strains. The influence and breakup of superstructures/aggregates gives a "rheological fingerprint", a function of the applied deformation and time scale (Pipkin space). A characteristic process time was found that scales exponentially with the overlap parameter with an exponent of 4/2, and is proposed to represent the relaxation process of the superstructure in solution. PMID- 27561502 TI - Fabrication of carbon/SiO2 composites from the hydrothermal carbonization process of polysaccharide and their adsorption performance. AB - In this work, carbon/SiO2 composites, using amylose and tetraethyl orthosilicate (TEOS) as raw materials, were successfully prepared by a facial hydrothermal carbonization process. The carbon/SiO2 composites were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Energy Dispersive Spectroscopy (EDS), transmission electron microscope (TEM), N2 adsorption and Thermogravimetric (TG) analysis. The composites, which were made up of amorphous SiO2 and amorphous carbon, were found to have hierarchical porous structures. The mass ratios of amylose and SiO2 and the hydrothermal carbonization time had significant effects on the morphology of the composites, which had three shapes including monodispersed spheres, porous pieces and the nano-fibers combined with nano-spheres structures. The adsorption performance of the composites was studied using Pb(2+) as simulated contaminants from water. When the mass ratio of amylose and SiO2 was 9/1, the hydrothermal time was 30h and the hydrothermal temperature was 180 degrees C, the adsorption capacity of the composites achieved to 52mg/g. Experimental data show that adsorption kinetics of the carbon/SiO2 composites can be fitted well by the Elovich model, while the isothermal data can be perfectly described by the Langmuir adsorption model and Freundlich adsorption model. The maximum adsorption capacity of the carbon/SiO2 composites is 56.18mgg(-1). PMID- 27561503 TI - Relationship between morphologies and mechanical properties of hydroxypropyl methylcellulose/hydroxypropyl starch blends. AB - Edible films from the blending hydroxypropyl methylcellulose (HPMC) with hydroxypropyl starch (HPS) have been developed. This work focuses on the relationship between morphologies and mechanical properties of such systems. To aid understanding of blend morphology, a new technique used to identify the two phases through dying of the HPS by iodine has been developed, which provided a simple and convenient way to clearly distinguish between HPMC and HPS phases. It was found that the blend system is immiscible and there is phase transition point depending on blending ratio and solution concentration. The lower transparency point of the blend and phase transition reign of HPMC from continuous phase to separated phase correspond with the variation of tensile modulus. The modulus and elongation decreased with increased solution concentration, which is correlatable with the morphologies present, where it was found that the HPMC gradually changed from a continuous phase to a distinct phase. PMID- 27561505 TI - Characterization of a novel edible film based on gum ghatti: Effect of plasticizer type and concentration. AB - The feasibility of using gum ghatti (GG) as a novel film-forming material was investigated. Physical, barrier, mechanical and optical properties were determined as a function of GG content, plasticizer type and concentration. Sorbitol-GG films had lower moisture content, water contact angle, water vapor permeability and oxygen permeability but higher water solubility than glycerol-GG ones. Tensile strength and elastic modulus of films decreased whereas elongation at break increased with plasticizer concentration. GG films tended to be green and yellow. Film's total color difference increased and whiteness index decreased with plasticizer concentration. Glass transition temperature of films decreased with increasing plasticizer concentration. Smooth and regular surface morphology without phase separation between film's components were ascertained using scanning electron micrograph. X-ray diffraction revealed an amorphous-crystalline structure of GG films and crystallinity index decreased with increasing plasticizer concentration. GG has a promising potential in edible films production. PMID- 27561504 TI - Effects of different polysaccharides on the formation of egg yolk LDL complex nanogels for nutrient delivery. AB - Five polysaccharides, pectin, carboxymethyl cellulose (CMC), gum arabic, carrageenan and alginate, were studied to form complex nanogels with egg yolk low density lipoprotein (LDL). All nanogels were smaller than 85nm with high negative zeta potential, while LDL/carrageenan and LDL/alginate nanogels exhibited more heterogeneous size distribution. Fourier transform infrared spectrum suggested that hydrogen bonds, hydrophobic and electrostatic interactions were involved to form nanogels. Overall, significant expansion of nanogels was observed after encapsulation of curcumin, being studied as a model lipophilic nutrient. Fluorescence spectra evidenced that LDL provided non-polar microenvironment for curcumin and polysaccharides played an important role in the encapsulation process. All nanogels showed sustained release of curcumin under simulated gastrointestinal conditions. Furthermore, nanoscale, smooth and spherical ultrafine dry powders of nanogels were obtained by innovative nano spray drying technology. Our study indicated that LDL/polysaccharides may serve as potential oral delivery systems for lipophilic nutrients. PMID- 27561506 TI - Delignification outperforms alkaline extraction for xylan fingerprinting of oil palm empty fruit bunch. AB - Enzyme hydrolysed (hemi-)celluloses from oil palm empty fruit bunches (EFBs) are a source for production of bio-fuels or chemicals. In this study, after either peracetic acid delignification or alkaline extraction, EFB hemicellulose structures were described, aided by xylanase hydrolysis. Delignification of EFB facilitated the hydrolysis of EFB-xylan by a pure endo-beta-1,4-xylanase. Up to 91% (w/w) of the non-extracted xylan in the delignified EFB was hydrolysed compared to less than 4% (w/w) of that in untreated EFB. Alkaline extraction of EFB, without prior delignification, yielded only 50% of the xylan. The xylan obtained was hydrolysed only for 40% by the endo-xylanase used. Hence, delignification alone outperformed alkaline extraction as pretreatment for enzymatic fingerprinting of EFB xylans. From the analysis of the oligosaccharide fingerprint of the delignified endo-xylanase hydrolysed EFB xylan, the structure was proposed as acetylated 4-O-methylglucuronoarabinoxylan. PMID- 27561507 TI - Examination of the dyeing properties of pigment printing fabrics in a water ethanol mixed solvent. AB - We examined the dyeing properties of pigment printing fabrics in a water-ethanol mixed solvent. SEM, infrared spectroscopy, XRD, and rheological studies were carried out to understand the results. The K/S values of all pigment printing fabrics initially increased prior to a subsequent decrease, as can be observed from SEM images of the fabric surfaces. Viscosity tests indicated that variations in the dyeing performance in the mixed solvent could be mainly attributed to the quality of the thickener. Through examination of the rheological properties of the NaAlg paste and the IR spectra of the NaAlg membrane, ethanol appeared to weaken the hydrogen bonds between the NaAlg chains and water molecules, leading to more compact and disordered NaAlg chains. As the rubbing fastness remained relatively constant upon increasing the colour depth of the printing fabrics, this indicated the potential for broadening the application range of such a system. PMID- 27561508 TI - TEMPO-mediated oxidation on galactomannan: Gal/Man ratio and chain flexibility dependence. AB - Guar (GG) and locust bean (LBG) galactomannans (GMs) oxidation at C-6 was performed with catalyst TEMPO, in which the reaction progress was monitored by consume of NaOH solution. The products were characterized by spectroscopic analysis, infrared, and (1)H-nuclear magnetic resonance, confirming the presence of aldehydes groups as intermediate of reaction to carboxylic acid. From high performance anion exchange chromatography with pulsed amperometric detection Man/Gal molar ratio was determined and demonstrated a preference to oxidize Man during the reaction on both GMs, following a first order kinetics of oxidation. The comparative macromolecular behavior of native and oxidized GMs was obtained through the analysis by high performance size exclusion chromatography, and the persistence length (Lp) was 6nm and 4nm to native LBG and GG, respectively. A more accessible OH-6 at mannose residue in LBG could be related with a two times faster reaction than GG. The selective oxidation with catalyst TEMPO proved to be efficient to increase the flexibility of the GMs during oxidation. Short reaction time and beta-elimination process were mainly observed to LBG, probably due to a more favorable oxidation access to the polysaccharide main chain. PMID- 27561509 TI - Characterization of glycol chitosan grafted with low molecular weight polyethylenimine as a gene carrier for human adipose-derived mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) have a great capacity for self-renewal while still maintaining their multipotency, and can differentiate into a variety of cell types. The delivery of genes to a site of injury is a current and interesting field of gene therapy. In the present study, we describe a nonviral gene delivery carrier, glycol chitosan-methyl acrylate-polyethylenimine (GMP) polymer targeted towards human adipose-derived mesenchymal stem cells (AD-MSCs). Transfection efficiency, using luciferase (Luc) and a pDNA encoding enhanced green fluorescent protein (EGFP), along with cytotoxicity assays, were performed in human AD-MSCs. The results show that the transfection efficiency of the GMP polymer was similar to that of PEI25kD, and the cytotoxicity was lower. Moreover, human AD-MSCs were treated with the GMP polymer/pDNA polyplex and its cellular uptake and distribution were analyzed by flow cytometry and confocal microscopy. Furthermore, we performed endosomal escape analysis using LysoTracker Red, and found that the conjugated GMP polymer could escape from the endosome to the cytosol. Human AD-MSCs treated with the GMP polymer maintained their potential for osteogenic differentiation and phenotypic expression of human AD-MSCs based on flow cytometry analysis. The present study demonstrates that the GMP polymer can be used as a potential targeted-delivery carrier for effective gene delivery. PMID- 27561511 TI - Structural characterization of fucosylated chondroitin sulfates from sea cucumbers Apostichopus japonicus and Actinopyga mauritiana. AB - Two samples of fucosylated chondroitin sulfate (FCS), AJ and AM, were isolated from holothurian species Apostichopus japonicus and Actinopyga mauritiana, respectively. Purification of FCS was performed by ion exchange chromatography followed by gel filtration. Structure of the biopolymers was elucidated using chemical and NMR spectroscopic methods. Both polysaccharides were shown to contain a typical chondroitin core built up of repeating disaccharide units ->3) beta-d-GalNAc-(1->4)-beta-d-GlcA-(1-> and decorated by sulfate groups and alpha-l Fuc branches. Two polysaccharides were different in pattern of sulfation of GalNAc and fucosyl branches connected to O-3 of GlcA. The ratio of GalNAc4S6S:GalNAc4S for AJ was about 2:1, whereas for AM this value was approximately 1:1. AJ contained Fucp2S4S and Fucp3S4S residues linked to O-3 of GlcA in a ratio of 3:1, while for AM this ratio was 1:4. Small portions of Fucp4S units attached to O-3 of GlcA were also found in both polysaccharides. Moreover, in a structure of AM the presence of Fucp3S residues linked to O-6 of GalNAc were determined using the data of NMR spectra. PMID- 27561510 TI - Antioxidant and hepatoprotective activities of polysaccharides from Anoectochilus roxburghii. AB - The physicochemical properties (molecular weights and monosaccharide compositions), antioxidant and hepatoprotective activities of polysaccharides (ARPPs: ARPP30, ARPP60 and ARPP80) isolated from Anoectochilus roxburghii were investigated. ARPP80 exhibited relatively strong antioxidant activities in a concentration-dependent manner. In mice subjected to carbon tetrachloride-induced hepatotoxicity, ARPP80 pretreatment significantly (p<0.01) reduced the levels of aspartate and alanine amino transferases and malonyldialdehyde, prominently (p<0.01) restored the levels of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione in serum or liver homogenate. These hepatoprotective effects were comparable to those of the standard drug silymarin at the same dose (200mg/kg). The study clearly demonstrated that ARPPs, especially ARPP80, might be suitable as functional foods or hepatoprotective drugs. PMID- 27561512 TI - A multipurpose natural and renewable polymer in medical applications: Bacterial cellulose. AB - Bacterial cellulose (BC) produced by some bacteria, among them Gluconacetobacter xylinum, which secrets an abundant 3D networks fibrils, represents an interesting emerging biocompatible nanomaterial. Since its discovery BC has shown tremendous potential in a wide range of biomedical applications, such as artificial skin, artificial blood vessels and microvessels, wound dressing, among others. BC can be easily manipulated to improve its properties and/or functionalities resulting in several BC based nanocomposites. As example BC/collagen, BC/gelatin, BC/Fibroin, BC/Chitosan, etc. Thus, the aim of this review is to discuss about the applicability in biomedicine by demonstrating a variety of forms of this biopolymer highlighting in detail some qualities of bacterial cellulose. Therefore, various biomedical applications ranging from implants and scaffolds, carriers for drug delivery, wound-dressing materials, etc. that were reported until date will be presented. PMID- 27561513 TI - Furfural production in biphasic media using an acidic ionic liquid as a catalyst. AB - Ionic liquids are valuable tools for biorefineries. This study provides an experimental assessment on the utilization of an acidic ionic liquid (1-butyl-3 methylimidazolium hydrogen sulfate) as a catalyst for furfural production in water/solvent media. The substrates employed in experiments were commercial xylose (employed as a reference compound) or hemicellulosic saccharides obtained by hydrothermal processing of Eucalyptus globulus wood (which were employed as produced, after membrane concentration or after freeze-drying). A variety of reaction conditions (defined by temperature, reaction time and type of organic solvent) were considered. The possibility of recycling the catalyst was assessed in selected experiments. PMID- 27561514 TI - Synthesis and characterization of amylose grafted poly(acrylic acid) and its application in ammonia adsorption. AB - Amylose grafted poly(acrylic acid) (Am-g-PAA) was synthesized by graft copolymerization of amylose with acrylic acid. The structure of Am-g-PAA was confirmed by (1)H NMR and FT-IR spectra. The morphology, crystallinity and thermal properties of amylose and Am-g-PAA were investigated by SEM, XRD and TGA, respectively. The highest degree of substitution (DS) of carboxyl group was 1.96 which was obtained after reacted for 1h at 60 degrees C. Acrylic acid to anhydroglucose mole ratio for DS was 19.81. It was found that a large number of carboxyl groups were grafted on the backbone of amylose. It was also found that ammonia adsorption capacity of amylose increased by grafting poly(acrylic acid) on the backbone of amylose. PMID- 27561515 TI - Shape-controlled synthesis of cubic-like selenium nanoparticles via the self assembly method. AB - The ability to control the morphology of nanoparticles by molecular design and synthesis is gaining increasing attention for achieving improved unique properties. In this work, we designed the chemical structure of a stabilizer for controlling the shape of selenium nanoparticles (SeNPs) via a self-assembly process. When folic acid-gallic acid-N,N,N-trimethyl chitosan (FA-GA-TMC) was used as a stabilizer, SeNPs were observed to self-organize into cubic-like structures with an average size of approximately 300nm. In contrast to the product obtained when unmodified chitosan was used as a stabilizer, this method resulted in spherical shape with an average size of approximately 200nm. The data suggested that the cubic-like SeNPs were controlled by a combination of electrostatic interaction, pi-pi stacking and hydrogen bonding between neighboring particles. Furthermore, the cubic-like SeNPs exhibited good anticancer efficacy and cellular uptake against breast cancer cells while exhibiting low toxicity against normal cells. These data demonstrates a simple approach for the shape-controlled synthesis of cubic-like SeNPs for biological applications via the self-assembly method. PMID- 27561516 TI - Morphological influence of cellulose nanoparticles (CNs) from cottonseed hulls on rheological properties of polyvinyl alcohol/CN suspensions. AB - The present work describes the isolation of cellulose nanoparticles (CNs) with different morphologies and their influence on rheological properties of CN and CN poly (vinyl alcohol) (PVA) suspensions. Cottonseed hulls were used for the first time to extract three types of CNs, including fibrous cellulose nanofibers, rod like cellulose nanocrystals and spherical cellulose nanoparticles through mechanical and chemical methods. Rheology results showed that the rheological behavior of the CN suspensions was strongly dependent on CN concentration and particle morphology. For PVA/CN systems, concentration of PVA/CN suspension, morphology of CNs, and weight ratio of CN to PVA were three main factors that influenced their rheology behaviors. This research reveals the importance of CN morphology and composition concentration on the rheological properties of PVA/CN, providing new insight in preparing high performance hydrogels, fibers and films base on PVA/CN suspension systems. PMID- 27561517 TI - Recent insights on applications of pullulan in tissue engineering. AB - Tissue engineering is a recently emerging line of act which assists the regeneration of damaged tissues, unable to self-repair themselves and in turn, enhances the natural healing potential of patients. The repair of injured tissue can be induced with the help of some artificially created polymer scaffolds for successful tissue regeneration. The pullulan composite scaffolds can be used to enhance the proliferation and differentiation of cells for tissue regeneration. The unique pattern of pullulan with alpha-(1->4) and alpha-(1->6) linkages along with the presence of nine hydroxyl groups on its surface, endows the polymer with distinctive physical features required for tissue engineering. Pullulan can be used for vascular engineering, bone repair and skin tissue engineering. Pullulan composite scaffolds can also be used for treatment of injured femoral condyle bone, skull bone and full thickness skin wound of murine models, transversal mandibular and tibial osteotomy in goat, etc. This review article highlights the latest developments on applications of pullulan and its derivatives in tissue engineering. PMID- 27561518 TI - A novel approach for grafting of beta-cyclodextrin onto wool via laccase/TEMPO oxidation. AB - This study demonstrated a new enzymatic methodology to graft beta-cyclodextrin onto wool. The primary hydroxyl groups in beta-cyclodextrin were oxidized to aldehyde groups using laccase/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), which reacted with the amino groups of wool to form Schiff bases. The effects of treatment conditions (treatment temperature, laccase dosage, TEMPO dosage, treatment time) on the aldehyde and carboxyl contents in beta-cyclodextrin were studied. FTIR spectrum of oxidized beta-cyclodextrin showed the presence of aldehyde and carboxyl groups. Results of MALDI-TOF mass spectroscopy confirmed the coupling of beta-cyclodextrin to tyrosine, which was used as a model compound for wool. ATR-FTIR spectroscopy of the grafted wool confirmed the presence of beta-cyclodextrin in grafted wool and the formation of a Schiff base between beta cyclodextrin and wool. PMID- 27561519 TI - Effect of PEGylated chitosan as multifunctional stabilizer for deacetyl mycoepoxydience nanosuspension design and stability evaluation. AB - Here a series of multifunctional stabilizers was designed and used in a nanosuspension stability enhancement study. Methoxypolyethylene glycol (M PEG) grafted chitosan, accompanied by space steric hindrance, an electrostatic repulsion function, and a solvation effect, is a multifunctional stabilizer. Deacetyl mycoepoxydience (DM) nanosuspension was prepared using the anti-solvent precipitation approach. The effects of the DM and the multifunctional stabilizer concentration, solvent to anti-solvent ratio, crystallization and storage temperature, and ultrasonic time on drug particle formation during the anti solvent processing were investigated and the nanosuspension stability was studied. The nanosuspension showed dendritic-like nanostructures and a crystalline state in a morphology and crystalline state study. The optimized drug and multifunctional stabilizer concentration range were selected through the response surface optimization method. The most appropriate and stable nanosuspension could be obtained through the optimal parameters. This study demonstrated that M PEG-grafted chitosan (M PEGC) could be used as a multifunctional stabilizer to control particle size and improve nanosuspension stability. PMID- 27561520 TI - Structural characterization and anti-cancerous potential of gallium bioactive glass/hydrogel composites. AB - A bioactive glass series (0.42SiO2-0.10Na2O-0.08CaO-(0.40-X)ZnO-(X)Ga2O3) was incorporated into carboxymethyl cellulose (CMC)/dextran (Dex) hydrogels in three different amounts (0.05, 0.10, and 0.25m(2)), and the resulting composites were characterized using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and (13)C Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (CP MAS-NMR). Composite extracts were also evaluated in vitro against MG-63 osteosarcoma cells. TEM confirmed glass distribution throughout the composites, although some particle agglomeration was observed. DSC revealed that glass composition and content did have small effects on both Tg and Tm. MAS-NMR revealed that both CMC and Dex were successfully functionalized, that cross linking occurred, and that glass addition did slightly alter bonding environments. Cell viability analysis suggested that extracts of the glass and composites with the largest Ga-content significantly decreased MG-63 osteosarcoma viability after 30days. This study successfully characterized this composite series, and demonstrated their potential for anti-cancerous applications. PMID- 27561521 TI - Layered chitosan-collagen hydrogel/aligned PLLA nanofiber construct for flexor tendon regeneration. AB - The aim of our study was to develop a tendon construct of electrospun aligned poly (l-lactic acid) (PLLA) nanofibers, to mimic the aligned collagen fiber bundles and layering PLLA fibers with chitosan-collagen hydrogel, to mimic the glycosaminoglycans of sheath ECM for tendon regeneration. The hydrogel coated electrospun membrane was rolled and an outer coating of alginate gel was given to prevent peritendinous adhesion. The developed constructs were characterized by SEM, FT-IR and tensile testing. Protein adsorption studies showed lower protein adsorption on coated scaffolds compared to uncoated scaffolds. The samples were proven to be non-toxic to tenocytes. The chitosan-collagen/PLLA uncoated scaffolds and alginate gel coated chitosan-collagen/PLLA scaffolds showed good cell proliferation. The tenocytes showed good attachment and spreading on the scaffolds. This study indicated that the developed chitosan collagen/PLLA/alginate scaffold would be suitable for flexor tendon regeneration. PMID- 27561522 TI - Chitosan-based membranes with different ionic crosslinking density for pharmaceutical and industrial applications. AB - Chitosan membranes (Ch), ionically crosslinked with pentasodium tripolyphosphate (TPP), were prepared using chitosan of medium and high molecular weight of similar degree of deacetylation and different crosslinking conditions. An effect of synthesis conditions (pH of crosslinking TPP solution equal to 5.5 and 9.0) on molecular and supermolecular structure and on crosslinking density of Ch/TPP membranes was confirmed using Fourier transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WAXD) method and energy dispersive X-ray (EDX) spectrometry. Atomic-force microscopy (AFM) and contact angle measurements indicated some differences in membrane roughness and hydrophilicity. The state of water in non-crosslinked and ionically crosslinked Ch membranes containing different amount of water was investigated by low temperature differential scanning calorimetry (DSC) measurements. DSC analysis confirmed presence of freezing and non-freezing water in non-crosslinked and ionically crosslinked membranes. The amount of non-freezing water generally decreased after Ch crosslinking and was affected by crosslinking conditions and crosslinking density. Molecular weight of Ch had only slight influence on all characterized properties of ionically crosslinked membranes. PMID- 27561524 TI - Structural, antioxidant, and emulsifying activities of fucoidan from Saccharina japonica using pressurized liquid extraction. AB - Pressurized liquid extraction (PLE) was utilized to extract sulfated polysaccharides (fucoidan) from brown seaweed Saccharina japonica. Various conditions of temperature (80-200 degrees C), pressure (5-100bar), and solvents (water, 0.1% sodium hydroxide, 0.1% formic acid, 70% ethanol, 50% ethanol, and 25% ethanol) were assessed; the best crude fucoidan (CF) yield was 8.23%, obtained from 140 degrees C and 50bar (sodium hydroxide). Compositional analysis, FT-IR, molecular weight, monosaccharides, TGA, UV-vis, XRD, and elemental analysis confirm that extracted polysaccharides revealed the features of fucoidan. Fucose was the main monosaccharide present in CF obtained by various solvent systems. All CF showed antioxidant activities as measured by DPPH radical and ABTS(+) radical scavenging. CF demonstrates good emulsion-stabilizing capacities, especially with vegetable oils. This study demonstrates that PLE is an efficacious method for enhancing the yield of polysaccharides from S. japonica and that it could be a potential source of natural antioxidants and emulsifiers. PMID- 27561523 TI - Rapid preparation of functional polysaccharides from Pyropia yezoensis by microwave-assistant rapid enzyme digest system. AB - This study describes a simple preparation of functional polysaccharides from Pyropia yezoensis using a microwave-assistant rapid enzyme digest system (MAREDS) with various carbohydrases, and evaluates their antioxidative effects. Polysaccharide hydrolysates were prepared using MAREDS under different hydrolytic conditions of the carbohydrases and microwave powers. Polysaccharides less than 10kDa (Low molecular weight polysaccharides, LMWP, <=10kDa) were efficiently obtained using an ultrafiltration (molecular weight cut-off of 10kDa). MAREDS increases AMG activation via an increased degree of hydrolysis; the best AMG hydrolysate was prepared using a 10:1 ratio of substrate to enzyme for 2h in MAREDS with 400W. LMWP consisted of galactose (27.3%), glucose (64.5%), and mannose (8.3%) from the AMG hydrolysate had stronger antioxidant effects than the high molecular weight polysaccharides (>10kDa). We rapidly prepared functional LMWPs by using MAREDS with carbohydrases, and suggest that LMWP might be potentially a valuable algal polysaccharide antioxidant. PMID- 27561525 TI - Amidated pectin/sodium carboxymethylcellulose microspheres as a new carrier for colonic drug targeting: Development and optimization by factorial design. AB - The colon is a promising site for drug targeting owing to its long transit time and mild proteolytic activity. The aim of this study was to prepare new low methoxy amidated pectin/NaCMC microspheres cross-linked by a mixture of Zn(2+) and Al(3+) ions and test their potential for colonic targeting of progesterone. A 2(4) factorial design was carried out to optimize the preparation conditions. High drug entrapment efficiency (82-99%) was obtained and it increased with increasing drug concentration but decreased with increasing polymer concentration. Drug release rate was directly proportional to the microsphere drug content and inversely related to Al(3+) ion concentration. Drug release was minimal during the first 3h but was significantly improved in the presence of 1% rat caecal contents, confirming the microsphere potential for colonic delivery. The microspheres achieved >2.3-fold enhancement of colonic progesterone permeability. These results confirm the viability of the produced microspheres as colon-targeted drug delivery vehicle. PMID- 27561526 TI - Changes in crystal structure and physicochemical properties of potato starch treated by induced electric field. AB - The effects of induced electric field (IEF) on the crystal structure and physicochemical properties of potato starch were investigated by subjecting identically treated control and electrically-modified samples to the same temperature history. Additionally, a method of combining IEF with heating for efficient modification of native polymer was also proposed. Results showed that the application of IEF at an electric voltage of 75V has a statistically significant effect on starch gelatinization and pasting properties, especially when combined with heating at 50 degrees C. After treatment by the combination method for 96h, the gelatinization temperatures increased, which can be explained by the slight increase in the ratio of 1044/1015cm(-1) and relative crystallinity. Furthermore, IEF reduced granular swelling and therefore contributed to decreasing the peak, breakdown, and setback viscosity of potato starch. This study explores the potential of IEF as innovative technology for starch modification. PMID- 27561527 TI - Facile approach to prepare drug-loading film from hemicelluloses and chitosan. AB - This study introduces a facile and green route to fabricate film from bio-based polymers. The film has been prepared by the cross-linking reaction of quaternized hemicelluloses (QH) and chitosan (CHO) with epichlorohydrin (ECH) as crosslinker. It exhibits an excellently mechanical performance as a result of its high tensile strength (up to 37MPa). Importantly, the roughness of film was 2-5nm in the area of 400nm, and smooth surface with pores were presented on the film based on the results of scanning electron microscope (SEM) and atomic force microscope (AFM). Ciprofloxacin was utilized as a mode compound to investigate the loading behavior of the film, and the highest loading concentration was about 18%. The drug release was about 20% in film1 in comparison to only 15% in film3 within 48h. Furthermore, the results of a 293T cell viability assay indicated its good biocompatibility and non-toxicity. PMID- 27561528 TI - In-situ polymerized cellulose nanocrystals (CNC)-poly(l-lactide) (PLLA) nanomaterials and applications in nanocomposite processing. AB - CNC-PLLA nanomaterials were synthesized via in-situ ring-opening polymerization of l-lactide in the presence of CNC, resulting in hydrophobic, homogeneous mixture of PLLA-grafted-CNC and free PLLA homopolymer. The free PLLA serves two useful functions: as barrier to further prevent PLLA-g-CNC from forming aggregates, and in creating improved interfacial properties when these nanomaterials are blended with other polymers, hence enhancing their performance. CNC-PLLA nanomaterials can be used for medical or engineering applications as they-are or by compounding with suitable biopolymers using versatile techniques, such as solution casting, co-extrusion or injection molding, to form hybrid nanocomposites of tunable mechanical properties. When compounded with commercial grade PLA, the resulting CNC-PLA nanocomposites appear transparent and have tailored (dynamic and static) mechanical and barrier properties, approaching those of poly(ethylene terephthalate), PET. The effect of reaction conditions on the properties of CNC-PLLA nanomaterials have been carefully studied and detailed throughout the paper. PMID- 27561529 TI - Design of starch functionalized biodegradable P(MAA-co-MMA) as carrier matrix for l-asparaginase immobilization. AB - We prepared biodegradable P(MAA-co-MMA)-starch composite as carrier matrix for the immobilization of l-asparaginase (l-ASNase), an important chemotherapeutic agent in acute lymphoblastic leukemia. Chemical characteristics and thermal stability of the prepared composites were determined by FT-IR, TGA, DTA and, DSC, respectively. Also, biodegradability measurements of P(MAA-co-MMA)-starch composites were carried out to examine the effects of degradation of the starch. Then, l-ASNase was immobilized on the P(MAA-co-MMA)-starch composites. The surface morphology of the composite before and after immobilization was characterized by SEM, EDX, and AFM. The properties of the immobilized l-ASNase were investigated and compared with the free enzyme. The immobilized l-ASNase had better showed thermal and pH stability, and remained stable after 30days of storage at 25 degrees C. Thus, based on the findings of the present work, the P(MAA-co-MMA)-starch composite can be exploited as the biocompatible matrix used for l-ASNase immobilization for medical applications due to biocompatibility and biodegradability. PMID- 27561530 TI - Preparation of guar gum scaffold film grafted with ethylenediamine and fish scale collagen, cross-linked with ceftazidime for wound healing application. AB - Present study describes the synthesis of carboxymethyl guar gum (CMGG) from the native guar gum (GG) and the prepared CMGG is grafted with ethylenediamine (EDA) to form aminated CMGG. Then, fish scale collagen and aminated CMGG are cross linked by ceftazidime drug through non- covalent ionic interaction. The resultant cross-linked film is subjected to the analysis of (1)HNMR, ATR-FTIR, TGA, SEM and XRD. The TNBS results revealed that 45% of interaction between EDA and CMGG and 90-95% of Ceftazidime is released from aminated CMGG-Ceftazidime-Collagen (ACCC) film after 96h of incubation at physiological pH. In vitro cell line studies reveal the biocompatibility of the cross-linked film and the antimicrobial studies display the growth inhibition against Staphylococcus aureus and Pseudomonas aeruginosa organisms. Overall, the study indicates that the incorporation of Ceftazidime into collagen and aminated CMGG can improve the functional property of aminated CMGG as well as collagen, leading to its biomedical applications. PMID- 27561531 TI - Synthesis and characterization of polyurethane-cellulose acetate blend membrane for chromium (VI) removal. AB - Blended membranes of polyurethane and cellulose acetate were prepared, characterized and investigated for their performance. Various ratios of cellulose acetate were employed to prepare four different blend membranes. The characteristics of both pure and blend membranes were investigated and results were compared to distinguish their properties. Functional group analysis was carried out by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) of pure and blend samples. Contact angle measurement and water content were evaluated to determine the membrane hydrophilicity. Moreover, the membrane morphology was studied by scanning electron microscopy (SEM). The membrane permeation properties and ability to reject chromium (VI) ions were tested at various pH and pressure by utilizing different salt concentrations. PMID- 27561532 TI - Enhanced mechanical, thermal and antimicrobial properties of poly(vinyl alcohol)/graphene oxide/starch/silver nanocomposites films. AB - In the present work, synthesis of poly(vinyl alcohol)/graphene oxide/starch/silver (PVA/GO/Starch/Ag) nanocomposites films is reported. Such films have been characterized and investigated for their mechanical, thermal and antimicrobial properties. The exfoliation of GO in the PVA matrix occurs owing to the non-covalent interactions of the polymer chains of PVA and hydrophilic surface of the GO layers. Presence of GO in PVA and PVA/starch blends were found to enhance the tensile strength of the nanocomposites system. It was found that the thermal stability of PVA as well as PVA/starch blend systems increased by the incorporation of GO where strong physical bonding between GO layers and PVA/starch blends is assumed to cause thermal barrier effects. Antimicrobial properties of the prepared films were investigated against Escherichia coli and Staphylococcus aureus. Our results show enhanced antimicrobial properties of the prepared films where PVA-GO, PVA-Ag, PVA-GO-Ag and PVA-GO-Ag-Starch showed antimicrobial activity in ascending order. PMID- 27561533 TI - Potential applications of cellulose and chitosan nanoparticles/composites in wastewater treatment: A review. AB - This work concerns the investigation of potential candidature of cellulose and chitosan-based nano-sized materials for heavy metals and dyes removal. Cellulose and chitosan being the first two abundant biopolymers in nature offer wide opportunities to be utilized for high-end applications such as water purification. The nano-sized cellulose and nano-sized chitosan present superior adsorption behavior compared to their micro-sized counterparts. This area of research which explores the possible usage of nano-biopolymers is relatively new. The present review article outlines the development history of research in the field of cellulose and chitosan, various methods employed for the functionalization of the biopolymers, current stage of research, and mechanisms involved in adsorption of heavy metals and dyes using nanocellulose and nanochitosan. The significance of research using nano-biopolymers and future prospects are also identified. PMID- 27561534 TI - Surface stiffening and enhanced photoluminescence of ion implanted cellulose - polyvinyl alcohol - silica composite. AB - Novel Cellulose (Cel) reinforced polyvinyl alcohol (PVA)-Silica (Si) composite which has good stability and in vitro degradation was prepared by lyophilization technique and implanted using N(3+) ions of energy 24keV in the fluences of 1*10(15), 5*10(15) and 1*10(16)ions/cm(2). SEM analysis revealed the formation of microstructures, and improved the surface roughness on ion implantation. In addition to these structural changes, the implantation significantly modified the luminescent, thermal and mechanical properties of the samples. The elastic modulus of the implanted samples has increased by about 50 times compared to the pristine which confirms that the stiffness of the sample surface has increased remarkably on ion implantation. The photoluminescence of the native cellulose has improved greatly due to defect site, dangling bonds and hydrogen passivation. Electric conductivity of the ion implanted samples was improved by about 25%. Hence, low energy ion implantation tunes the mechanical property, surface roughness and further induces the formation of nano structures. MG63 cells seeded onto the scaffolds reveals that with the increase in implantation fluence, the cell attachment, viability and proliferation have improved greatly compared to pristine. The enhancement of cell growth of about 59% was observed in the implanted samples compared to pristine. These properties will enable the scaffolds to be ideal for bone tissue engineering and imaging applications. PMID- 27561535 TI - Structure characterization of three polysaccharides and a comparative study of their immunomodulatory activities on chicken macrophage. AB - In this study, we evaluated structure characterization and immunomodulatory activity of polysaccharides from Astragalus aboriginum Richardson (RAPS), Atractylodes macrocephala Koidz (RAMPS) and Rumia seseloides Hoffm (RSPS) in vitro on chicken macrophage. We found that molecular weight of RAPS and RAMPS was 122.4 and 109.4kDa higher than 64.71kDa of RSPS. Glucose occupied 83.95% and 66.39% in RAPS and RAMPS, respectively. RSPS mainly contained glucose and galacturonic acid, which accounted for 32.35% and 29.25%, respectively. The NMR results displayed that RAPS and RAMPS contained beta- glucose, beta-galactose, and beta-galacturonic acid. The backbone was 1->6 linked glucose. RSPS showed at least six monosaccharide response signals. In vitro experiment, the results showed that RAPS at dosage of 15.62MUgmL(-1) exhibited significant immunological on chicken macrophage compared to RAMPS and RSPS. Interestingly, costimulatory molecules levels in RSPS group were higher than that of RAPS, which may associated with the special structure of RSPS. PMID- 27561536 TI - Properties of modified carboxymethyl cellulose and its use as bioactive compound. AB - The present study deals with synthesizing novel cellulose derivative, from modifying the carboxymethyl cellulose with amino phenylpropanoic acid (CMC-APP). The synthesized CMC-APP was evaluated as biological and anti-cancer active compound. The molecular structures of this active compound were built using the HyperChem program 7.5, together with conventional analysis (nitrogen content, FT IR, and non-isothermal TGA analysis). Optimizing the CMC/APPA ratio was carried out as preliminary assessment step, via undetected antimicrobial activity measurement. The TEM study showed that, the synthesized cellulose CMC-APP derivative in the nano-scale particle size (range from 12.5 to 89.3nm). Among all the tested microorganisms and MCF-7 breast cancer cells, the synthesized nano cellulose derivative is possible used as safety medicine for microbial infections and cancers. The minimal inhibitory concentration (MIC) for Gram-positive bacteria, and gram-negative bacteria are 48.82MUg/mL and 97MUg/mL, respectively. While, the unicellular fungi and filamentous fungi are 12.2MUg/mL and 97.65MUg/mL, respectively. The cytotoxic index (IC50) for MCF-7 breast cancers is 50MUg/mL. Moreover, the computational study of ADMET (absorption, distribution, metabolism, elimination and toxic) properties, of the molecules showed that, this investigated nano-compound is good oral bioavailability. PMID- 27561537 TI - Microfabrication of a tunable collagen/alginate-chitosan hydrogel membrane for controlling cell-cell interactions. AB - Indirect cell contact co-culture system is increasingly becoming more attractable owing to their advantages of easy cell separation and desirable outcomes for cell cell interactions. However, how to precisely control the spatial position of cells within multicellular co-cultures is still experimentally challenging due to the incapability of the conventional methods in vitro. In the present study, a tunable collagen/alginate-chitosan (Col/Alg-Chi) membrane was established, which was capable of controlling intercellular distance between the neighboring cells at a level of micrometer resolution. It was showed that intercellular distance between the hepatocytes and the fibroblasts exerted significant influence on hepatic function in vitro. In particular, maintenance of the functionality of primary hepatocytes requires direct contact between the hepatocytes and their supportive stromal cells, and their effective contact distance is within 30MUm. This technical platform would potentially enable investigations of dynamic cell cell interaction in a multitude of applications including organogenesis, development or even neoplastic transformation. PMID- 27561538 TI - Recent advances in tea polysaccharides: Extraction, purification, physicochemical characterization and bioactivities. AB - Tea has a long history of medicinal and dietary use. Tea polysaccharide (TPS) is regarded as one of the main bioactive constituents of tea and is beneficial for health. Over the last decades, considerable efforts have been devoted to the studies on TPS: extraction, structural feature and bioactivity of TPS. However, it has been received much less attention compared with tea polyphenols. In order to provide new insight for further development of TPS in functional foods, in present review we summarize the recent literature, update the information and put forward future perspectives on TPS covering its extraction, purification, quantitative determination techniques as well as physicochemical characterization and bioactivities. PMID- 27561540 TI - Acetylation of bacterial cellulose catalyzed by citric acid: Use of reaction conditions for tailoring the esterification extent. AB - Bacterial cellulose (BC) nanoribbons were partially acetylated by a simple direct solvent-free route catalyzed by citric acid. The assay of reaction conditions within chosen intervals (i.e. esterification time (0.5-7h), catalyst content (0.08-1.01mmol/mmol AGU), and temperature (90-140 degrees C)), illustrated the flexibility of the methodology proposed, with reaction variables which can be conveniently manipulated to acetylate BC to the required degree of substitution (DS) within the 0.20-0.73 interval. Within this DS interval, characterization results indicated a surface-only process in which acetylated bacterial cellulose with tunable DS, preserved fibrous structure and increased hydrophobicity could be easily obtained. The feasibility of reusing the catalyst/excess acylant in view of potential scale-up was also illustrated. PMID- 27561539 TI - Structural characterization and inhibition on alpha-d-glucosidase activity of non starch polysaccharides from Fagopyrum tartaricum. AB - In the present study, the crude polysaccharide was extracted from Fagopyrum tartaricum and purified by Sephadex G-25 and G-75 column to produce a polysaccharide fraction termed TBP-II. Its average molecular weight was 26kDa. The structural characterization of TBP-II was investigated by gas chromatography, periodate oxidation-Smith degradation, Methylation and NMR. Congo red was applied to explore its advanced structures. The results revealed that chemical composition and structural characteristic of TBP-II was mainly consisted of galactose, arabinose, xylose and glucose with a molar ratio of 0.7:1:6.3:74.2. The backbone of TBP-II was composed of (1->4)-linked alpha-d-glucopyranosyl (Glcp), while the branches comprised of (1->3)-linked alpha-d-glucopyranosyl (Glcp), (1->6)-linked alpha-d-galactopyranosyl (Galp) and (1->2,4)-linked alpha-d rhamnopyranosyl (Rhap). The structure of TBP-II was 1,3 and 1,6-branched galactorhamnoglucan that had a linear backbone of (1->4)-linked alpha-d glucopyranose (Glcp). Using Congo red assay showed that it was absent of triple helix structure. The alpha-d-glucosidase inhibitory activity of TBP-II was determined using acarbose as positive control. The result showed that the inhibition rate depended on the concentration of polysaccharides. PMID- 27561541 TI - Germination and microwave processing of barley (Hordeum vulgare L) changes the structural and physicochemical properties of beta-d-glucan & enhances its antioxidant potential. AB - The nutraceutical potential of beta-d-glucan is largely dependent on its structure, size and viscosity. The present study analyzed the effect of germination and microwave processing of barley on the structural, size, antioxidant and thermal characteristics of beta-d-glucan. The molecular weight and viscosity of beta-d-glucan obtained from germinated barley (GGB) were the lowest (144kDa and 37.33cp) as compared to beta-d-glucan from microwave processed barley (GMB) and unprocessed barley (GUB). The GGB exhibited higher antioxidant potential than GMB and GUB. The Structural elucidation by ATR-FTIR revealed scission in polymeric chain and beta glycosydic linkage of beta-d-glucan obtained from processed barley. The highest peak intensity at glycosydic linkage in GGB confirms more scission in the molecule. The DSC curve of GGB showed the highest transition temperature. It was concluded that germination of barley can be a good approach for enhancing the antioxidant potential of beta-d-glucan. PMID- 27561542 TI - Corrigendum to "Pretreatment with xylanase and its significance in hemicelluloses removal from mixed hardwood kraft pulp as a process step for viscose" [Carbohydr. Polym. 145 (2016) 95-102]. PMID- 27561543 TI - Inferring the Skeletal Muscle Developmental Changes of Grazing and Barn-Fed Goats from Gene Expression Data. AB - Thirty-six Xiangdong black goats were used to investigate age-related mRNA and protein expression levels of some genes related to skeletal muscle structural proteins, MRFs and MEF2 family, and skeletal muscle fiber type and composition during skeletal muscle growth under grazing (G) and barn-fed (BF) feeding systems. Goats were slaughtered at six time points selected to reflect developmental changes of skeletal muscle during nonrumination (days 0, 7, and 14), transition (day 42), and rumination phases (days 56 and 70). It was observed that the number of type IIx in the longissimus dorsi was increased quickly while numbers of type IIa and IIb decreased slightly, indicating that these genes were coordinated during the rapid growth and development stages of skeletal muscle. No gene expression was affected (P > 0.05) by feeding system except Myf5 and Myf6. Protein expressions of MYOZ3 and MEF2C were affected (P < 0.05) by age, whereas PGC-1alpha was linearly decreased in the G group, and only MYOZ3 protein was affected (P < 0.001) by feeding system. Moreover, it was found that PGC-1alpha and MEF2C proteins may interact with each other in promoting muscle growth. The current results indicate that (1) skeletal muscle growth during days 0-70 after birth is mainly myofiber hypertrophy and differentiation, (2) weaning affects the expression of relevant genes of skeletal muscle structural proteins, skeletal muscle growth, and skeletal muscle fiber type and composition, and (3) nutrition or feeding regimen mainly influences the expression of skeletal muscle growth genes. PMID- 27561544 TI - Latent AKI is... still AKI: the quantification of the burden of renal dysfunction. AB - The association between pediatric cardiac surgery, acute kidney injury (AKI), and clinical outcomes has been studied several times in the recent literature. In this issue of Critical Care an interesting and original study analyzed the path from causal AKI entities to clinical AKI consequences through the application of structural equation modeling. The authors described the complex connections linking duration of cardiopulmonary bypass, cross clamp-time, and descriptors of low cardiac output syndrome to AKI modeled as a complex variable composed of post operative serum creatinine increase of 50 % over baseline, urine output <0.5 ml/kg/h, and urine creatinine-normalized neutrophil gelatinase lipocalin within 12 h of surgery. Similarly, the causal relationships between AKI and hard outcomes in the analyzed population were verified and quantified. The authors, for the first time, produce a repeatable coefficient (0.741) that may become a useful quality benchmark and could be applied to test future interventions aiming to reduce the burden of AKI on children's clinical course. PMID- 27561545 TI - Colloidal cholesteric liquid crystal in spherical confinement. AB - The organization of nanoparticles in constrained geometries is an area of fundamental and practical importance. Spherical confinement of nanocolloids leads to new modes of packing, self-assembly, phase separation and relaxation of colloidal liquids; however, it remains an unexplored area of research for colloidal liquid crystals. Here we report the organization of cholesteric liquid crystal formed by nanorods in spherical droplets. For cholesteric suspensions of cellulose nanocrystals, with progressive confinement, we observe phase separation into a micrometer-size isotropic droplet core and a cholesteric shell formed by concentric nanocrystal layers. Further confinement results in a transition to a bipolar planar cholesteric morphology. The distribution of polymer, metal, carbon or metal oxide nanoparticles in the droplets is governed by the nanoparticle size and yields cholesteric droplets exhibiting fluorescence, plasmonic properties and magnetic actuation. This work advances our understanding of how the interplay of order, confinement and topological defects affects the morphology of soft matter. PMID- 27561546 TI - A Novel Surface Structure Consisting of Contact-active Antibacterial Upper-layer and Antifouling Sub-layer Derived from Gemini Quaternary Ammonium Salt Polyurethanes. AB - Contact-active antibacterial surfaces play a vital role in preventing bacterial contamination of artificial surfaces. In the past, numerous researches have been focused on antibacterial surfaces comprising of antifouling upper-layer and antibacterial sub-layer. In this work, we demonstrate a reversed surface structure which integrate antibacterial upper-layer and antifouling sub-layer. These surfaces are prepared by simply casting gemini quaternary ammonium salt waterborne polyurethanes (GWPU) and their blends. Due to the high interfacial energy of gemini quaternary ammonium salt (GQAS), chain segments containing GQAS can accumulate at polymer/air interface to form an antibacterial upper-layer spontaneously during the film formation. Meanwhile, the soft segments composed of polyethylene glycol (PEG) formed the antifouling sub-layer. Our findings indicate that the combination of antibacterial upper-layer and antifouling sub-layer endow these surfaces strong, long-lasting antifouling and contact-active antibacterial properties, with a more than 99.99% killing efficiency against both gram-positive and gram-negative bacteria attached to them. PMID- 27561547 TI - Cell non-autonomous regulation of hepatic IGF-1 and neonatal growth by Kinase Suppressor of Ras 2 (KSR2). AB - Individuals with poor postnatal growth are at risk for cardiovascular and metabolic problems as adults. Here we show that disruption of the molecular scaffold Kinase Suppressor of Ras 2 (KSR2) causes selective inhibition of hepatic GH signaling in neonatal mice with impaired expression of IGF-1 and IGFBP3. ksr2( /-) mice are normal size at birth but show a marked increase in FGF21 accompanied by reduced body mass, shortened body length, and reduced bone mineral density (BMD) and content (BMC) first evident during postnatal development. However, disrupting FGF21 in ksr2(-/-) mice does not normalize mass, length, or bone density and content in fgf21(-/-)ksr2(-/-) mice. Body length, BMC and BMD, but not body mass, are rescued by infection of two-day-old ksr2(-/-) mice with a recombinant adenovirus encoding human IGF-1. Relative to wild-type mice, GH injections reveal a significant reduction in JAK2 and STAT5 phosphorylation in liver, but not in skeletal muscle, of ksr2(-/-) mice. However, primary hepatocytes isolated from ksr2(-/-) mice show no reduction in GH-stimulated STAT5 phosphorylation. These data indicate that KSR2 functions in a cell non-autonomous fashion to regulate GH-stimulated IGF-1 expression in the liver of neonatal mice, which plays a key role in the development of body length. PMID- 27561548 TI - Relationships between otolith and fish size from Mediterranean and north-eastern Atlantic species to be used in predator-prey studies. AB - Regressions between fish length and otolith size are provided for 40 species from the north-eastern Atlantic Ocean and 142 species from the Mediterranean Sea. Regressions were also estimated at genus level. Most of the regressions (c. 84%) explained a high percentage of the deviance (>75%). PMID- 27561550 TI - Within-pair differences of DNA methylation levels between monozygotic twins are different between male and female pairs. AB - BACKGROUND: DNA methylation levels will be important for detection of epigenetic effects. However, there are few reports showing sex-related differences in the sensitivity to DNA methylation. To evaluate their sex-related individual differences in the sensitivity to methylation rigorously, we performed a systematic analysis of DNA methylation in monozygotic twins, an optimal model to evaluate them because the genetic backgrounds are the same. RESULTS: We examined 30 male and 43 female older monozygotic twin pairs recruited from the registry established by the Center for Twin Research, Osaka University. Their methylation levels were determined using the Infinium HumanMethylation450 BeadChip Kit (Illumina), which interrogated 485577 highly informative CpG sites at the single nucleotide resolution, and the median methylation level was calculated for each of the 25657 CpG islands. Within-pair differences of methylation levels (WPDMs) were greater in male pairs than female pairs for 86.0 % of autosomal CpG islands, but were higher in female pairs than male pairs for 76.7 % of X chromosomal CpG islands. Mean WPDMs of CpG islands in each autosomal chromosome were significantly higher in male pairs than in female whereas that in X chromosome was significantly higher in female pairs than in male. Multiple comparison indicated that WPDMs in three autosomal and two X-chromosomal CpG islands were significantly greater in male pairs, whereas those in 22 X-chromosomal CpG islands were significantly greater in female pairs. CONCLUSION: Sex-related differences were present in the WPDMs of CpG islands in individuals with the same genetic background. These differences may be associated with the sexual influences in susceptibility of some diseases. PMID- 27561552 TI - Insight into the template effect of vesicles on the laccase-catalyzed oligomerization of N-phenyl-1,4-phenylenediamine from Raman spectroscopy and cyclic voltammetry measurements. AB - We report about the first Raman spectroscopy study of a vesicle-assisted enzyme catalyzed oligomerization reaction. The aniline dimer N-phenyl-1,4 phenylenediamine (= p-aminodiphenylamine, PADPA) was oxidized and oligomerized with Trametes versicolor laccase and dissolved O2 in the presence of sodium bis(2 ethylhexyl)sulfosuccinate (AOT) vesicles (80-100 nm diameter) as templates. The conversion of PADPA into oligomeric products, poly(PADPA), was monitored during the reaction by in situ Raman spectroscopy. The results obtained are compared with UV/vis/NIR and EPR measurements. All three complementary methods indicate that at least some of the poly(PADPA) products, formed in the presence of AOT vesicles, resemble the conductive emeraldine salt form of polyaniline (PANI-ES). The Raman measurements also show that structural units different from those of "ordinary" PANI-ES are present too. Without vesicles PANI-ES-like products are not obtained. For the first time, the as-prepared stable poly(PADPA)-AOT vesicle suspension was used directly to coat electrodes (without product isolation) for investigating redox activities of poly(PADPA) by cyclic voltammetry (CV). CV showed that poly(PADPA) produced with vesicles is redox active not only at pH 1.1 as expected for PANI-ES-but also at pH 6.0, unlike PANI-ES and poly(PADPA) synthesized without vesicles. This extended pH range of the redox activity of poly(PADPA) is important for applications. PMID- 27561549 TI - Structural and functional plasticity of dendritic spines - root or result of behavior? AB - Dendritic spines are multifunctional integrative units of the nervous system and are highly diverse and dynamic in nature. Both internal and external stimuli influence dendritic spine density and morphology on the order of minutes. It is clear that the structural plasticity of dendritic spines is related to changes in synaptic efficacy, learning and memory and other cognitive processes. However, it is currently unclear whether structural changes in dendritic spines are primary instigators of changes in specific behaviors, a consequence of behavioral changes, or both. In this review, we first examine the basic structure and function of dendritic spines in the brain, as well as laboratory methods to characterize and quantify morphological changes in dendritic spines. We then discuss the existing literature on the temporal and functional relationship between changes in dendritic spines in specific brain regions and changes in specific behaviors mediated by those regions. Although technological advancements have allowed us to better understand the functional relevance of structural changes in dendritic spines that are influenced by environmental stimuli, the role of spine dynamics as an underlying driver or consequence of behavior still remains elusive. We conclude that while it is likely that structural changes in dendritic spines are both instigators and results of behavioral changes, improved research tools and methods are needed to experimentally and directly manipulate spine dynamics in order to more empirically delineate the relationship between spine structure and behavior. PMID- 27561551 TI - Integrative proteomic profiling of ovarian cancer cell lines reveals precursor cell associated proteins and functional status. AB - A cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III). We identify a 67 protein cell line signature, which separates our entire proteomic data set, as well as a confirmatory publicly available CPTAC/TCGA tumour proteome data set, into a predominantly epithelial and mesenchymal HGSOC tumour cluster. This proteomics-based epithelial/mesenchymal stratification of cell lines and human tumours indicates a possible origin of HGSOC either from the fallopian tube or from the ovarian surface epithelium. PMID- 27561553 TI - The function of the PduJ microcompartment shell protein is determined by the genomic position of its encoding gene. AB - Bacterial microcompartments (MCPs) are complex organelles that consist of metabolic enzymes encapsulated within a protein shell. In this study, we investigate the function of the PduJ MCP shell protein. PduJ is 80% identical in amino acid sequence to PduA and both are major shell proteins of the 1,2 propanediol (1,2-PD) utilization (Pdu) MCP of Salmonella. Prior studies showed that PduA mediates the transport of 1,2-PD (the substrate) into the Pdu MCP. Surprisingly, however, results presented here establish that PduJ has no role 1,2 PD transport. The crystal structure revealed that PduJ was nearly identical to that of PduA and, hence, offered no explanation for their differential functions. Interestingly, however, when a pduJ gene was placed at the pduA chromosomal locus, the PduJ protein acquired a new function, the ability to mediate 1,2-PD transport into the Pdu MCP. To our knowledge, these are the first studies to show that that gene location can determine the function of a MCP shell protein. We propose that gene location dictates protein-protein interactions essential to the function of the MCP shell. PMID- 27561555 TI - Prevention is better than...? PMID- 27561554 TI - FFPred 3: feature-based function prediction for all Gene Ontology domains. AB - Predicting protein function has been a major goal of bioinformatics for several decades, and it has gained fresh momentum thanks to recent community-wide blind tests aimed at benchmarking available tools on a genomic scale. Sequence-based predictors, especially those performing homology-based transfers, remain the most popular but increasing understanding of their limitations has stimulated the development of complementary approaches, which mostly exploit machine learning. Here we present FFPred 3, which is intended for assigning Gene Ontology terms to human protein chains, when homology with characterized proteins can provide little aid. Predictions are made by scanning the input sequences against an array of Support Vector Machines (SVMs), each examining the relationship between protein function and biophysical attributes describing secondary structure, transmembrane helices, intrinsically disordered regions, signal peptides and other motifs. This update features a larger SVM library that extends its coverage to the cellular component sub-ontology for the first time, prompted by the establishment of a dedicated evaluation category within the Critical Assessment of Functional Annotation. The effectiveness of this approach is demonstrated through benchmarking experiments, and its usefulness is illustrated by analysing the potential functional consequences of alternative splicing in human and their relationship to patterns of biological features. PMID- 27561556 TI - Orthodontics: Allergic to the orthodontist? PMID- 27561557 TI - Accidental ice-burn. PMID- 27561558 TI - Dental trauma: Smartphone hazards. PMID- 27561559 TI - Medical emergencies: Trivialising the dentist. PMID- 27561560 TI - Dental education: Admission troubles. PMID- 27561561 TI - The last of my kind? PMID- 27561562 TI - A highly competitive environment. PMID- 27561565 TI - Does floss have a future? PMID- 27561570 TI - Symposium on communication skills in healthcare delivery. PMID- 27561571 TI - Taking stock of training in implant dentistry. AB - Despite the ever-growing demand for implant treatments by patients, there is confusion about what the appropriate training pathway in implant dentistry should be. This is accompanied by a worrying lack of training at undergraduate level for correct patient selection and monitoring of implant cases. An unclear training pathway, inappropriate referrals and a 'hands-off' approach to patients with implants may be putting patients at risk. This article highlights these issues with a suggestion that the training should of course follow the current GDC guidelines, but goes further to suggest that the end point of training should be at diploma level as a minimum, either via a university route, or via the RCS Edinburgh Diploma in Implant Dentistry Examination. PMID- 27561572 TI - The restorative management of microdontia. AB - Microdontia is a dental abnormality that will often present to the dental practitioner due to the aesthetic concerns of the patient. Treatment is therefore aimed at addressing the aesthetics issue of the patient and this can present a number of challenges which may require a multidisciplinary approach in its management. This article presents the restorative management of localised and generalised microdontia. PMID- 27561573 TI - A personal perspective and update on erosive tooth wear - 10 years on: Part 2 - Restorative management. AB - The management challenge with erosive tooth wear is that the condition involves erosion and contributions from attrition and abrasion, both of which impact on the longevity of restorations. Severe erosive tooth wear results in visibly shorter teeth, exposure of dentine and adaptive changes which complicate restorative management. There is increasing evidence to suggest if the risk factors, such as reducing the frequency of acidic foods and drinks, are reduced the progression of tooth wear slows and follows a normal pattern of wear. But once teeth become shorter patients often seek advice from dentists on restorative intervention. Composite restorations are successful in some patients but they often involve regular maintenance with repairs and rebuilds, which for some patients is unacceptable. Full coverage crowns, although destructive of tooth tissue, remain an option for restorations. PMID- 27561574 TI - Dental effects of methamphetamine: Methamphetamine users have increased dental disease: a propensity score analysis. AB - Although 'not consistently as extreme as depicted in earlier reports,' those who use methamphetamine show more extensive caries. PMID- 27561575 TI - Life course epidemiology: Oral health-related beliefs, behaviors, and outcomes through the life course. AB - '..self-reported oral health by the age of 38 y... is influenced by intergenerational factors and various aspects of our beliefs, socioeconomic position, dental attendance, and self-care, which operate over the years since childhood.' PMID- 27561576 TI - '...A brain functionally addicted to pain': The emotional brain as a predictor and amplifier of chronic pain. AB - Chronic pain would appear to be disorders in neural networks; not as a consequence of nociceptive barrage to the cortex. PMID- 27561577 TI - The impact of oral conditions on children in England, Wales and Northern Ireland 2013. AB - Background The 2013 Children's Dental Health survey is the fifth in a series of national surveys.Aim To summarise key findings on oral health perceptions, oral symptoms, and the impacts of oral conditions on the daily life of children and their families.Methodology A representative sample of children (aged 5, 8 12 and 15 years) and their parents in England, Wales and Northern Ireland completed relevant questionnaires.Results Oral symptoms, even more profound ones such as toothache, were prevalent among all age groups. Overall, 58% of 12- and 45% of 15 year-olds reported at least one oral impact in the past three months. The most prevalent oral impact was feeling embarrassed to smile or laugh, followed by difficulty eating. These symptoms and oral impacts were disproportionately high among children eligible for free school meals. Furthermore, one fifth to one third of parents reported that their children's oral conditions had some impact on their family life.Conclusion Oral symptoms were common and oral conditions had a negative impact on the quality of life of large proportions of children. There were clear and marked socioeconomic inequalities, with considerably worse oral health perceptions and higher levels of oral impacts among the more deprived children. PMID- 27561578 TI - Chair-side preventive interventions in the Public Dental Service in Norway. AB - Objective and setting In Norway, the Public Dental Service (PDS) caters for the young (<19 years) and smaller numbers of adults, mostly special needs patients. This study surveyed chair-side preventive measures used in the public clinics and compared them with recommendations in evidence-based guidelines in the neighbouring countries.Materials and methods After ethical approval, the regional Chief Dental Officers (CDOs) emailed questionnaires to their local clinics (N = 421) where the most experienced dentist and dental hygienist were asked to respond on behalf of the clinic. Answers were received from 256 clinics (response rate 61%). Altogether, 215 dentists and 166 dental hygienists answered.Results Of the respondents, 26% reported that their clinic had agreed guidelines on preventive treatment to be used by all staff. Oral hygiene and fluoride toothpaste recommendations were considered appropriate. Almost 60% claimed that flossing instructions were given to all children and adolescents and 40% that fluoride varnish was used on all the young. Fissure sealants were used after individual assessment (80%). A third of the respondents claimed that fluoride tablets and fluoride rinse were recommended for all or most children and fluoride rinses for adults, even in addition to regular use of fluoride toothpaste. Dental hygienists used all methods more often than dentists. On adults, preventive measures were more often used on individual assessment. Half (48%) of the respondents were interested in new evidence-based national guidelines on preventive care.Conclusions Chair-side preventive treatment measures were numerous in the well-resourced Norwegian PDS, but partly outdated. PMID- 27561579 TI - What I wish I'd learned at dental school. AB - Background Much concern appears to exist as to the scope and content of contemporary dental school programmes, with the oft-cited criticism being made that dental graduates are 'no longer as good as they used to be'.Aim The aim of this project was to survey the views of dentists - both new graduates and more established practitioners - on aspects of their own dental school training they felt had been deficient as well as commenting on what aspects of dental school education they would like to see improved/enhanced in current times.Methods An invitation to complete an Internet-based questionnaire was emailed to the Fellows and Members of the Faculty of General Dental Practice (UK). Topics in the questionnaire included the respondent's own dental education history, how well they felt their dental school training had covered certain clinical and non clinical topics; and their opinions on areas they felt should be included in contemporary dental school programmes.Results Six hundred and forty-nine responses were received from 3,348 emailed invitations (response rate = 19.4%). Sixty-one percent (395) of respondents were qualified for 10 years or more. Among clinical skills and techniques, a majority of respondents reported they felt they had not had sufficient teaching/training in dental school in surgical endodontics (76%), conscious sedation (72%), root surface debridement (71%), fixed orthodontic appliances (68%), porcelain veneers (63%), implants (56%) and posterior composites (53%). If designing a new dental school programme, the most common topics respondents would seek to include/increase were business and practice management (21%), communication skills (including patient management and leadership skills) (10%), and increased clinical time and experience (8%).Conclusions The findings of this project are of interest and relevance to those working with student dentists and young dental practitioners. A greater emphasis is needed on the teaching of certain non-clinical subjects such as business and communication skills, while within clinical subjects there is need to refine and expand teaching in identified areas such as exodontia and endodontics. PMID- 27561580 TI - 'The Dentist's Hands': An analysis of the portrait by Fiona Graham-Mackay. AB - One hundred and fifty years ago, a dentist practising in Tavistock signed off a letter to the editor of The British Journal of Dental Science, 'Suaviter et Fortiter'. This paper discusses the commissioning from the eminent portrait painter Fiona Graham-Mackay of a painting of a dentist's hands. In the course of the sittings, the artist commented that as the mirror and probe were picked up, the hands took on an authority they did not have before. If the portrait is successful, it is so in demonstrating the gentle but firm authority, suaviter et fortiter, of the profession. PMID- 27561594 TI - DYNAMIC SONOGRAPHY OF THE EQUINE METACARPO(TARSO)PHALANGEAL DIGITAL FLEXOR TENDON SHEATH. AB - Palmar/plantar annular desmitis is a common disease that may be associated with adhesions and structures affecting the flexor tendons, which requires tenoscopy to diagnose. The purpose of this descriptive study was to develop a dynamic sonographic technique for evaluating the motion of normal equine flexor tendons in relation to the palmar/plantar annular ligament and to compare findings with horses previously diagnosed with palmar/plantar annular desmitis. Ten healthy adult horses were examined prospectively and the images of four horses diagnosed with palmar/plantar annular desmitis were retrospectively evaluated. Dynamic sonography was performed at the level of the metacarpo/metatarsophalangeal joint by maximally extending and flexing the interphalangeal joints. Palmar/plantar annular ligament thickness (mm), size of any gap between the flexor tendons, and subjectively increased angulation of the long linear echoes of the superficial digital flexor tendon were measured. The presence of gliding motion between the palmar/plantar annular ligament and superficial digital flexor tendon was determined by consensus. Twenty-eight healthy control limbs (16 hind/12 fore) and four with palmar/plantar annular desmitis (3 hind/1 fore) were evaluated. Controls had unrestricted gliding motion between the palmar/plantar annular ligament and flexor tendons and zero to 13 degrees of angulation of the long linear echoes. The four affected horses had restricted gliding motion and between 20-35 degrees angulation of the long linear echoes. Dynamic ultrasound is a feasible technique for detecting restricted flexor tendon and palmar/plantar annular ligament gliding motion, as well as subjectively increased angulation of the long linear echoes of the flexor tendon in affected horses compared with controls and warrants further investigation. PMID- 27561595 TI - Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks. AB - OBJECTIVES: To develop a model for the prediction of stillbirth that is based on a combination of maternal characteristics and medical history with first trimester biochemical and biophysical markers and to evaluate the performance of screening with this model for all stillbirths and those due to impaired placentation and unexplained causes. METHODS: This was a prospective screening study of 76 897 singleton pregnancies, including 76 629 live births and 268 (0.35%) antepartum stillbirths; 157 (59%) were secondary to impaired placentation and 111 (41%) were due to other or unexplained causes. Multivariable logistic regression analysis was used to determine if there was a significant contribution to prediction of stillbirth from the maternal factor-derived a-priori risk, fetal nuchal translucency thickness, ductus venosus pulsatility index for veins (DV PIV), uterine artery pulsatility index (UtA-PI) and maternal serum free beta human chorionic gonadotropin and pregnancy-associated plasma protein-A (PAPP-A). The significant contributors were used to derive a model for first-trimester prediction of stillbirth. RESULTS: Significant contribution to prediction of stillbirth was provided by maternal factors, PAPP-A, UtA-PI and DV-PIV. A model combining these variables predicted 40% of all stillbirths and 55% of those due to impaired placentation, at a false-positive rate of 10%. Within the impaired placentation group, the detection rate of stillbirth < 32 weeks' gestation was higher than that of stillbirth >= 37 weeks (64% vs 42%). CONCLUSIONS: A model based on maternal factors and first-trimester biomarkers can potentially predict more than half of subsequent stillbirths that occur due to impaired placentation. The extent to which such stillbirths could be prevented remains to be determined. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27561593 TI - Awareness of and reactions to mammography controversy among immigrant women. AB - BACKGROUND: There is substantial expert disagreement about the use of mammography to screen for breast cancer, and this disagreement routinely plays out in the media. Evidence suggests that some women are aware of the controversy over mammography, but less is known about whether immigrant and other underserved women have heard about it and, if so, how they react to it. OBJECTIVE: To explore immigrant women's awareness of and reactions to mammography controversy. DESIGN: Community-engaged qualitative study: we conducted six focus groups with 53 women aged 35-55 from three immigrant communities (Somali, Latina and Hmong) in a major US metropolitan area. A grounded theory approach was used to identify themes; NVivo 10 was used to enhance analyses. RESULTS: Several themes emerged: (i) low awareness of mammography controversy across groups, despite self-reported attention to health information; (ii) high intentions to be screened, even after being told about the controversy; (iii) few reported discussions of mammography's risks and benefits with clinicians; (iv) substantial interest in learning more about mammography and breast cancer, but some low self-efficacy to obtain such information; and (v) questions about whether health recommendations matter and what qualifies as evidence. CONCLUSION: Given on-going expert disagreement about mammography screening, it is important for clinicians to help women understand mammography's risks and benefits so they can make an informed choice. This is particularly critical for immigrant and other underserved women, who may be less able to access, attend to, process, retain and act on health information (a phenomenon known as communication inequality). PMID- 27561596 TI - Antibiotic resistance in early periprosthetic joint infection. AB - BACKGROUND: Prophylactic antibiotics significantly reduce prosthetic joint infection (PJI) rates after hip and knee arthroplasty. However, rising antibiotic resistance has raised concerns over the adequacy of conventional prophylaxis. This study aimed to identify organisms causing PJIs in hip and knee arthroplasty secondary to perioperative contamination and their susceptibility to current prophylactic antibiotics. METHODS: We performed a retrospective audit of 4009 primary hip and knee arthroplasties (1852 hips and 2157 knees) at three tertiary referral hospitals. PJIs were identified according to the Infectious Diseases Society of America definition, and patients were followed-up for 2 years. For patients with confirmed PJIs, causative bacteria and their antibiotic susceptibilities were identified. RESULTS: Thirty-five PJI cases were identified (13 hips and 22 knees). The overall definite PJI rate was 0.87% (0.7% for hips, 1.0% for knees). Ninety-six percent of patients with PJI received cefazolin prophylaxis. Culture information was available for 30 cases. The most common infecting organisms were coagulase-negative staphylococci (CoNS), causing 35% of infections. Ninety-two percent of CoNS strains were cefazolin-resistant. Twenty five percent of patients were infected with Staphylococcus aureus, 9.1% of which were methicillin-resistant. Overall, 53% of infecting organisms were cefazolin resistant. CONCLUSIONS: The majority of bacteria causing early PJI are resistant to cefazolin. Whilst many organisms cultured were susceptible to vancomycin, there is currently insufficient evidence to justify its routine use as a prophylactic. However, when treating PJI in the early postoperative period, surgeons should be aware that most organisms will be methicillin-resistant, and the choice of empirical antibiotic treatment should reflect this. PMID- 27561597 TI - Position, position, position - terminology during stomach ultrasound in pregnant women. PMID- 27561598 TI - Cultural group selection follows Darwin's classic syllogism for the operation of selection. AB - The main objective of our target article was to sketch the empirical case for the importance of selection at the level of groups on cultural variation. Such variation is massive in humans, but modest or absent in other species. Group selection processes acting on this variation is a framework for developing explanations of the unusual level of cooperation between non-relatives found in our species. Our case for cultural group selection (CGS) followed Darwin's classic syllogism regarding natural selection: If variation exists at the level of groups, if this variation is heritable, and if it plays a role in the success or failure of competing groups, then selection will operate at the level of groups. We outlined the relevant domains where such evidence can be sought and characterized the main conclusions of work in those domains. Most commentators agree that CGS plays some role in human evolution, although some were considerably more skeptical. Some contributed additional empirical cases. Some raised issues of the scope of CGS explanations versus competing ones. PMID- 27561599 TI - Relationship between hyperemesis gravidarum and small-for-gestational-age in the Japanese population: the Japan Environment and Children's Study (JECS). AB - BACKGROUND: Small-for-gestational-age in infancy is a known risk factor not only for short-term prognosis but also for several long-term outcomes, such as neurological and metabolic disorders in adulthood. Previous research has shown that severe nausea and vomiting in early pregnancy (NVP) and hyperemesis gravidarum, which is an extreme form of NVP, represent risk factors for small-for gestational-age birth. However, there is no clear consensus on this association. Thus, in the present study, we investigated the correlation between hyperemesis gravidarum and NVP on the one hand, and infant birth weight on the other, using data from the Japan Environment and Children's Study (JECS). METHODS: The data utilized in the present study were obtained from the JECS, an ongoing cohort study that began in January 2011. Our sample size was 8635 parent-child pairs. The presence or absence of severe NVP, hyperemesis gravidarum, and potential confounding factors were noted. A multivariable regression analysis was used to estimate risks for small-for-gestational-age birth, and the results were expressed as risk ratios and 95 % confidence intervals. RESULTS: The risk ratios of small-for-gestational-age birth (95 % confidence interval) for mothers with severe NVP and those with hyperemesis gravidarum were 0.86 (0.62-1.19) and 0.81 (0.39-1.66), respectively, which represents a non-significant result. CONCLUSIONS: In our analysis of JECS data, neither severe NVP nor hyperemesis gravidarum was associated with increased risk for small-for-gestational-age birth. PMID- 27561600 TI - Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury. AB - BACKGROUND: Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. METHODS: To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to a closed head mild TBI (mTBI) by a standard controlled cortical impact, along with or without treatment of sphingosine 1-phosphate (S1P) or rolipram, after which the brain tissue of the impact site was evaluated for cell morphology via histology, inflammation by qRT-PCR and T cell staining, and cell death with Caspase-3 and TUNEL staining. Circulating lymphocytes were quantified by flow cytometry, and plasma hydrocortisone was analyzed by LC-MS/MS. To investigate the mechanism whereby cortisol lowered the number of peripheral T cells, T cell egress was tracked in lymph nodes by intravital confocal microscopy after hydrocortisone administration. RESULTS: We detected a decreased number of circulating lymphocytes, in particular, T cells soon after mTBI, which was inversely correlated with a transient and robust increase of plasma cortisol. The transient lymphocytopenia might be caused by cortisol in part via a blockade of lymphocyte egress as demonstrated by the ability of cortisol to inhibit T cell egress from the secondary lymphoid tissues. Moreover, exogenous hydrocortisone severely suppressed periphery lymphocytes in uninjured mice, whereas administering an egress-promoting agent S1P normalized circulating T cells in mTBI mice and increased T cells in the injured brain. Likewise, rolipram, a cAMP phosphodiesterase inhibitor, was also able to elevate cAMP levels in T cells in the presence of hydrocortisone in vitro and abrogate the action of cortisol in mTBI mice. The investigation demonstrated that the number of circulating T cells in the early phase of TBI was positively correlated with T cell infiltration and inflammatory responses as well as cell death at the cerebral cortex and hippocampus beneath the impact site. CONCLUSIONS: Decreases in intracellular cAMP might be part of the mechanism behind cortisol-mediated blockade of T cell egress. The study argues strongly for a protective role of cortisol-induced immune suppression in the early stage of TBI. PMID- 27561601 TI - HOGA1 Gene Mutations of Primary Hyperoxaluria Type 3 in Tunisian Patients. AB - BACKGROUND: Primary hyperoxaluria type 3 (PH3) is due to mutations in the recently identified 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. The aim of this study was to report three PH3 cases carrying mutations in HOGA1. MATERIALS AND METHODS: Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after sequencing of AGXT and GRHPR genes, which was negative. Also, a complete AGXT/GRHPR MLPA was performed in these patients in order to detect large deletions/insertions. RESULTS AND DISCUSSION: Two different HOGA1 gene mutations were identified: the p.Pro190Leu in a homozygous state and the p.Gly287Val in two patients in homozygous and heterozygous carriers. The median age at onset of clinical symptoms was 3.93 years. Most of the patients had a positive family history for recurrent urolithiasis. The p.Pro190Leu mutation was reported with impaired renal function at follow-up; however, the p.Gly287Val was presented with normal renal function. All patients were presented with urolithiasis, but only one had a nephrocalcinosis. CONCLUSION: This study expanded the number of PH3 patients from 63 to 66 cases. The p.Pro190Leu and the p.Gly287Val mutations found in this study can provide a first-line investigation in Tunisian PH1 patients. PMID- 27561603 TI - Linguistics, cognitive psychology, and the Now-or-Never bottleneck. AB - Christiansen & Chater (C&C)'s key premise is that "if linguistic information is not processed rapidly, that information is lost for good" (sect. 1, para. 1). From this "Now-or-Never bottleneck" (NNB), C&C derive "wide-reaching and fundamental implications for language processing, acquisition and change as well as for the structure of language itself" (sect. 2, para. 10). We question both the premise and the consequentiality of its purported implications. PMID- 27561604 TI - Suppressed GABAergic signaling in the zona incerta causes neuropathic pain in a thoracic hemisection spinal cord injury rat model. AB - OBJECTIVE: Suppression of the gamma-aminobutyric acid (GABA)ergic activity of the zona incerta (ZI) reportedly plays a role in neuropathic pain after spinal cord injury (SCI). A reduction in GABAergic signaling in the ZI of a thoracic hemisection-SCI rat model has been suggested, but not clearly demonstrated. Accordingly, our objective was to investigate whether GABAergic signals influence SCI-induced neuropathic pain. METHODS: In vivo, we recorded and compared single unit, neuronal activity between hemisection-SCI and sham-operated rat models. Furthermore, we analyzed neuronal activity in both models following treatment with either a GABAA receptor agonist (muscimol) or antagonist (bicuculline). RESULTS: Rats that underwent hemisection SCI exhibited reduced hindpaw withdrawal thresholds, latencies, and decreased ZI neuronal activity compared with sham operated controls. Importantly, muscimol treatment increased, whereas bicuculline decreased, the firing rates of the ZI neurons. The muscimol treated, hemisection SCI rats also exhibited increased hindpaw withdrawal thresholds and latencies. CONCLUSIONS: These data provide evidence that neuropathic pain after SCI is caused by decreased GABAergic signaling in the ZI. Furthermore, our data demonstrate that infusion of a GABAergic drug into the ZI could restore its inhibitory action and improve neuropathic pain behaviors. PMID- 27561605 TI - The cyclic nucleotide gated channel subunit CNG-1 instructs behavioral outputs in Caenorhabditis elegans by coincidence detection of nutritional status and olfactory input. AB - In mammals, olfactory subsystems have been shown to express seven-transmembrane G protein-coupled receptors (GPCRs) in a one-receptor-one-neuron pattern, whereas in Caenorhabditis elegans, olfactory sensory neurons express multiple G-protein coupled odorant receptors per olfactory sensory neuron. In both mammalian and C. elegans olfactory sensory neurons (OSNs), the process of olfactory adaptation begins within the OSN; this process of negative feedback within the mammalian OSN has been well described in mammals and enables activated OSNs to desensitize their response cell autonomously while attending to odors detected by separate OSNs. However, the mechanism that enables C. elegans to adapt to one odor and attend to another odor sensed by the same olfactory sensory neuron remains unclear. We found that the cyclic nucleotide gated channel subunit CNG-1 is required to promote cross adaptation responses between distinct olfactory cues. This change in sensitivity to a pair of odorants after persistent stimulation by just one of these odors is modulated by the internal nutritional state of the animal, and we find that this response is maintained across a diverse range of food sources for C. elegans. We also reveal that CNG-1 integrates food related cues for exploratory motor output, revealing that CNG-1 functions in multiple capacities to link nutritional information with behavioral output. Our data describes a novel model whereby CNG channels can integrate the coincidence detection of appetitive and olfactory information to set olfactory preferences and instruct behavioral outputs. PMID- 27561602 TI - Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549). AB - One molecular-based approach that increases potency and reduces dose-limited sequela is the implementation of selective 'targeted' delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine-monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine-(5' phosphoramidate)-[anti-IGF-1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine reactive gemcitabine-(5'-phosphorylimidazolide) intermediate. Monoclonal anti-IGF 1R immunoglobulin was combined with gemcitabine-(5'-phosphorylimidazolide) resulting in the synthetic formation of gemcitabine-(5'-phosphoramidate)-[anti IGF-1R]. The gemcitabine molar incorporation index for gemcitabine-(5' phosphoramidate)-[anti-IGF-R1] was 2.67:1. Cytotoxicity Analysis - dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine-equivalent concentrations of 10-9 M and 10-7 M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine-reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non-dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms. PMID- 27561607 TI - Realizing the Now-or-Never bottleneck and Chunk-and-Pass processing with Item Order-Rank working memories and masking field chunking networks. AB - Christiansen & Chater's (C&C's) key goals for a language system have been realized by neural models for short-term storage of linguistic items in an Item Order-Rank working memory, which inputs to Masking Fields that rapidly learn to categorize, or chunk, variable-length linguistic sequences, and choose the contextually most predictive list chunks while linguistic inputs are stored in the working memory. PMID- 27561608 TI - [Postpartum pelvic floor muscle training: Should absence of evidence justify absence of guidelines?] PMID- 27561606 TI - Software-based analysis of bacteriophage genomes, physical ends, and packaging strategies. AB - BACKGROUND: Phage genome analysis is a rapidly growing field. Recurrent obstacles include software access and usability, as well as genome sequences that vary in sequence orientation and/or start position. Here we describe modifications to the phage comparative genomics software program, Phamerator, provide public access to the code, and include instructions for creating custom Phamerator databases. We further report genomic analysis techniques to determine phage packaging strategies and identification of the physical ends of phage genomes. RESULTS: The original Phamerator code can be successfully modified and custom databases can be generated using the instructions we provide. Results of genome map comparisons within a custom database reveal obstacles in performing the comparisons if a published genome has an incorrect complementarity or an incorrect location of the first base of the genome, which are common issues in GenBank-downloaded sequence files. To address these issues, we review phage packaging strategies and provide results that demonstrate identification of the genome start location and orientation using raw sequencing data and software programs such as PAUSE and Consed to establish the location of the physical ends of the genome. These results include determination of exact direct terminal repeats (DTRs) or cohesive ends, or whether phages may use a headful packaging strategy. Phylogenetic analysis using ClustalO and phamily circles in Phamerator demonstrate that the large terminase gene can be used to identify the phage packaging strategy and thereby aide in identifying the physical ends of the genome. CONCLUSIONS: Using available online code, the Phamerator program can be customized and utilized to generate databases with individually selected genomes. These databases can then provide fruitful information in the comparative analysis of phages. Researchers can identify packaging strategies and physical ends of phage genomes using raw data from high-throughput sequencing in conjunction with phylogenetic analyses of large terminase proteins and the use of custom Phamerator databases. We promote publication of phage genomes in an orientation consistent with the physical structure of the phage chromosome and provide guidance for determining this structure. PMID- 27561609 TI - Computational Study of Anatomical Risk Factors in Idealized Models of Type B Aortic Dissection. AB - OBJECTIVE/BACKGROUND: Several risk factors have been identified in type B aortic dissection (TBAD), namely tear size, location, patency and number, and false lumen (FL) location. However, the individual impact of each of these factors is poorly understood. The impact of these factors was investigated using computational fluid dynamics (CFD). METHODS: Fourteen idealized models of chronic TBAD were created of different shapes (straight vs. curved vessels), different number of proximal and distal tears, tear size (4, 10, and 20 mm diameter) and shape (circular or elliptical), FL location (inner or outer arch), treated (stented), and untreated. All models had identical length, relative size of true lumen (TL) and FL, and inlet (flow) and outlet (pressure) boundary conditions. Using validated CFD tools, inlet mean pressure (MP), pulse pressure (PP), TL and FL pressures, velocities, and flows were computed for each model. RESULTS: AD increased PP and MP relative to undissected aorta. Curvature did not change pressure and flow ratio between TL and FL. Inner curvature FL showed slightly larger pressures and tear velocities. Larger tears decreased hemodynamic differences between TL and FL. The combination of proximal and distal tear size determines the overall hemodynamics: larger proximal tears increased FL PP by up to 76%. Conversely, larger distal tears decreased FL PP and MP. Large proximal and distal tears decreased tear velocity (by up to 65%) and increased FL flow (up to 12 times). Proximal tear stenting resulted in a 54% reduction of PP. Conversely, distal occlusion tear increased FL PP and MP by 144% and 7%, respectively. CONCLUSION: Unfavorable hemodynamic conditions such as larger FL pressure occur when distal tear is small or absent, proximal tears are large, and FL is at the inner curvature, in agreement with previous clinical studies. CFD analysis is a powerful tool to understand the interplay between anatomy and hemodynamics in TBAD. PMID- 27561610 TI - Editorial. PMID- 27561611 TI - Advanced UV Absorbers for the Protection of Human Skin. AB - The increasing awareness of the damaging effects of UV radiation to human skin triggered the market introduction of new cosmetic UV absorbers. This article summarizes the outcome of a multi-year research program, in which the author contributed to the development of different new UV filters. First of all, the molecular design and the basic properties of bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) will be presented. This oil-soluble filter, which today is widely used in both beach products and skin care products, exhibits inherent photostability and strong broad-spectrum UV-A+B absorbance. Based on the concept of micronized organic UV absorbers, the UV-B filter tris biphenyl triazine (TBPT) will be introduced. At present TBPT exhibits the highest efficacy of all cosmetic UV absorbers in the market (measured by area under the UV spectrum). Finally, the concept of liposomogenic UV absorbers will be featured. This approach was developed to create water-resistant UV filters, as liposomogenic structures are thought to integrate into the lipids of the horny layer. Due to prohibitively high costs, this technology did not result in a commercial product so far. PMID- 27561613 TI - Structure-Property Relations in Polymer:Fullerene Blends for Organic Solar Cells. AB - Organic solar cells consist of thin films combining an electron donor (often a conjugated polymer) with an electron acceptor (often a fullerene derivative), in a blend commonly referred to as bulk heterojunction material. Charge separation between the donor and the acceptor leads to the generation of carriers, which can be extracted from photovoltaic devices in the form of photocurrent. The generation mechanism of free, extractable charges has caused a lot of controversial discussion in literature. Our research has shown that all the steps involved in charge generation are strongly dependent on the arrangement of the donor and the acceptor (i.e. the structure) of the bulk heterojunction. PMID- 27561612 TI - Daring the Challenge and Thinking Big: The Value of Early Process R&D. AB - The production of the L/T channel blocker ACT-280778 required the enantiomerically pure 5-phenylbicyclo[2.2.2]oct-5-en-2-one (1) as key building block. As the published routes towards 1 are very low yielding (<0.5% yield) and comprise many steps that are not acceptable for scale-up, a series of processes to 1 was developed to match the increasing requirements from first kg-batches to clinical supplies. The three routes are characterized by an individual asset. (1) The first route contains a scale-up of a Diels-Alder reaction with highly reactive reagents and afforded 90 kg enantiomerically pure 1. To mitigate safety risks, a flow reactor was developed for the high-temperature Diels-Alder reaction. This route relied on an efficient enantiomer separation on a 1/4-ton scale by HPLC. (2) A Crystallization Induced Diastereomer Transformation (CIDT) during an intramolecular aldol reaction was the pivotal step of a first enantioselective route that starts with the Shibasaki reaction. (3) The 2(nd) enantioselective route represents a rare example of organocatalysis on scale and allowed to skip six out of nine steps with a significant impact on the cost of goods. This simple way to 1 opened up a short synthesis of Hayashi's chiral diene ligands (bod*) that were so far lacking an affordable access. Some of these novel C1-symmetrical dienes have shown very high enantioselectivities in Rh-catalyzed additions of arylboronates. PMID- 27561615 TI - Assessing Cannabis Consumption Frequency: Is the Quantification of Free and Glucuronidated THCCOOH in Blood the Key? PMID- 27561616 TI - International Relations at Universities of Applied Sciences. AB - An overview of international relations at the Universities of Applied Sciences in Switzerland is presented. PMID- 27561617 TI - Biocatalysis - Key Technology to Meet Global Challenges CCBIO Symposium at the 8(th) Waedenswil Day of Life Science. AB - In a world of dwindling fossil-based energy, global air pollution and warming, biocatalysis may be a perfect problem-solver. It has the potential to procure sustainable raw materials and energy from biomass, and enables chiral and highly functionalized compounds to be produced ecologically for the chemical and pharmaceutical industry. At ZHAW Waedenswil on June 20, 2016, the Competence Center for Biocatalysis (CCBIO) gave European experts the opportunity to present the latest findings from science, research and practice in the future-oriented field of biocatalysis. PMID- 27561619 TI - The 51(st) EUCHEMS Conference on Stereochemistry: The Burgenstock Tradition Continues. PMID- 27561618 TI - DMCCB Basel Symposium 2016 Macrocycles in Drug- and Agrochemical Discovery Symposium of the Division of Medicinal Chemistry and Chemical Biology (DMCCB) of the Swiss Chemical Society (SCS), Department of Chemistry, University of Basel, May 24(th), 2016. PMID- 27561621 TI - Brown adipose tissue: Updates in cellular and molecular biology. AB - Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP) -1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM) -16. The sympathetic nervous system centrally regulates thermogenesis through norepinephrine, which acts on the adrenergic receptors of BAT. This bound leads to the initialization of the many pathways that may activate thermogenesis in acute and/or chronic ways. In summary, this mini-review aims to demonstrate the latest advances in the knowledge of BAT. PMID- 27561622 TI - Differential activation of CD95-mediated apoptosis related proteins in proximal and distal tubules during rat renal development. AB - The CD95-mediated apoptotic pathway is the best characterized of the death receptor-mediated apoptotic pathways. The present study characterized localization and expression of proteins involved in CD95-mediated apoptosis during rat renal development. Kidneys were obtained from embryonic (E) 18 and 20 day-old fetuses and postnatal (P) 1-, 3-, 5-, 7-, 14-, and 21-day-old pups. Immunohistochemical characterization revealed that CD95, FasL and cleaved caspase 3 were strongly expressed in proximal tubules and weakly expressed in distal tubules, but that expression of caspase-8 in distal tubules was stronger than that in proximal tubules. Results from terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that levels of apoptosis in proximal tubules slowly increased after E18, while those of distal tubules slowly decreased after P5. Western blotting demonstrated that expression of CD95, FasL and FADD was very weak during embryonic development, but rapidly increased at P14. Expression of cleaved caspase-3 was maintained at high levels after P1, while caspase-8 expression gradually reached a peak at P7. Results from this study reveal that the CD95-mediated apoptotic pathway is a key driver of apoptosis in proximal tubules during late postnatal kidney development in rats and suggest that apoptosis in distal tubules is mediated by a different apoptotic pathway. PMID- 27561623 TI - Effect of different cell sheet ECM microenvironment on the formation of vascular network. AB - The repair and reconstruction of large bone defects remains as a significant clinical challenge mainly due to the insufficient vascularization. The prefabrication of vascular network based on cell sheet technique brings a promising potential for sufficient vascularization due to rich extracellular matrix (ECM) of cell sheets. However, the effect of different cell sheet ECM micro-environment on the formation of a vascular network has not been well understood. Here our goal is to study the effect of different cell sheets on the formation of a vascular network. First we cultured human bone marrow mesenchymal stem cells (hBMSCs) under two culture conditions to obtain osteogenic differentiated cell sheet (ODCS) and undifferentiated cell sheet (UDCS), respectively. Then the human umbilical vein endothelial cells (HUVECs) were seeded onto the surface of the two sheets at different seeding densities to fabricate pre-vascularized cell sheets. Our results indicated that the two sheets facilitated the alignment of HUVECs and promoted the formation of vascular networks. Quantitative analysis showed that the number of networks in ODCS was higher than that in the UDCS. The ECM of the two sheets was remodeled and rearranged during the tubulogenesis process. Furthermore, results showed that the optimal seeding density of HUVECs was 5*10(4)cell/cm(2). In summary, these results suggest that the vascularized ODCS has a promising potential to construct pre-vascularized tissue for bone repair. PMID- 27561624 TI - Beta 1,3/1,6-glucan and vitamin C immunostimulate the non-specific immune response of white shrimp (Litopenaeus vannamei). AB - This study mainly evaluated the effects of orally administered beta 1,3/1,6 glucan and vitamin C on the nonspecific immune responses of white shrimp (Litopenaeus vannamei). In this study, we found that the white shrimp oral administration with 1 g/kg of beta 1,3/1,6-glucan effectively enhanced O2(-) production and phenoloxidase and superoxide dismutase activity. Shrimp were oral administration with 0.2 g/kg of vitamin C presented beneficial nonspecific immune responses and enzyme activity and also observed in the beta 1,3/1,6-glucan treatment groups. Consequently, we compared the alterations in the immune activity between the beta 1,3/1,6-glucan and vitamin C groups and the evidence illustrated that combination of beta 1,3/1,6-glucan and vitamin C presented an additive effect on inducing the nonspecific immune responses of white shrimp. PMID- 27561625 TI - The cellular death pattern of primary haemocytes isolated from the black tiger shrimp (Penaeus monodon). AB - A key to successfully generate the penaeid shrimp cell line is to find out how primary cells died. The most suitable period to culture Penaeus monodon haemocytes was in the first 48 h of culture because cells had normal morphology, high percent of viable cells (65.29 +/- 5.43%), low percent of early (11.75 +/- 1.30%) and late apoptotic cells (15.47 +/- 11.71%) determined by Annexin V and TUNEL including constant IAP (0.06 +/- 0.01-0.07 +/- 0.01) and caspase-3 expression (0.30 +/- 0.06-0.39 +/- 0.10) by real-time PCR throughout the experiment. Moreover, adding 50 and 250 MUM of the cell permeable pan caspase inhibitor Z-VAD-FMK produced some melanised cells since the 48(th) hour, while percent of viable cells was decreased since the 24(th) hour with no difference in percent of early and late apoptotic cells compared to control at each time point. No difference of IAP and caspase-3 expression level in both Z-VAD-FMK groups was found compared to control and vehicle groups at each time point, excluding caspase-3 in 250 MUM Z-VAD-FMK at the 24(th) hour was higher than control and vehicle. Supplementing sodium fluoride (NaF) induced cell membrane damage and cellular shrinkage of primary haemocytes within 2 h. Even percent of viable cells was reduced down to zero and percent of late apoptotic cells was increased by 2 h of incubation in 25 and 50 mM NaF, IAP and caspase-3 in all NaF groups was not different from control. These results indicate that a number of primary haemocytes derived in this study die through the apoptotic process. PMID- 27561627 TI - Do Attending Surgeons and Residents See Eye To Eye? An Evaluation of the Accreditation Council For Graduate Medical Education Milestones in General Surgery Residency. AB - OBJECTIVE: The Accreditation Council for Graduate Medical Education requires accredited general surgery residencies to implement competency-based developmental outcomes in resident evaluations. Overall, 16 milestones are evaluated by a clinical competency committee (CCC). The milestones span 8 domains of surgical practice and 6 Accreditation Council for Graduate Medical Education clinical competencies. The highest level suggests preparedness for independent practice. Our objective was to compare self-assessments and committee evaluations within the milestone framework. STUDY DESIGN: All residents underwent semiannual evaluations from 2013 to 2015. Residents independently completed a self assessment using the milestones. The CCC completed the milestones document using resident evaluations and consensus opinion of committee members. Assessment differences were calculated for each evaluation. A negative value indicated that the residents evaluated themselves at a lower level than the committee. Major assessment disparities were defined as >0.5 on a 4-point scale. SETTING: An independent academic medical center. PARTICIPANTS: General surgery residents. RESULTS: Overall, 20 residents participated; 7 were female. In total, 5 (7%) evaluations had a mean overall assessment difference >0.5, whereas 6 (8%) had a difference <-0.5. Residents evaluated themselves lower than the committee with a median assessment difference of -0.06 [-0.25 to 0.16] (p = 0.041). Evaluations were similar across surgical domains. Negative self-evaluations were more common for medical knowledge (-0.25 [-0.25 to 0.25], p = 0.025). Female residents had 2% positive and 13% negative major assessment disparity rates versus 10% positive and 9% negative rates among male residents. Postgraduate year III residents had 12% positive and 4% negative major disparity rates; all other years had higher negative than positive rates. CONCLUSIONS: Surgery residents within our program demonstrated adequate self-awareness, with most self-evaluations falling within a half level of the CCC report. This self-awareness was consistent across surgical domains and most clinical competencies. Residents perceived a lower level of medical knowledge than the CCC. Subgroup analysis revealed interesting trends in the effects of sex, postgraduate year level, and academic year timing, which will take additional study to fully delineate. PMID- 27561626 TI - Recent insights into the cell immobilization technology applied for dark fermentative hydrogen production. AB - The contribution and insights of the immobilization technology in the recent years with regards to the generation of (bio)hydrogen via dark fermentation have been reviewed. The types of immobilization practices, such as entrapment, encapsulation and adsorption, are discussed. Materials and carriers used for cell immobilization are also comprehensively surveyed. New development of nano-based immobilization and nano-materials has been highlighted pertaining to the specific subject of this review. The microorganisms and the type of carbon sources applied in the dark hydrogen fermentation are also discussed and summarized. In addition, the essential components of process operation and reactor configuration using immobilized microbial cultures in the design of varieties of bioreactors (such as fixed bed reactor, CSTR and UASB) are spotlighted. Finally, suggestions and future directions of this field are provided to assist the development of efficient, economical and sustainable hydrogen production technologies. PMID- 27561628 TI - A Checklist Intervention to Assess Resident Diagnostic Knee and Shoulder Arthroscopic Efficiency. AB - PURPOSE: The purpose of this investigation was to apply an arthroscopic shoulder and knee checklist in the evaluation of orthopedic resident arthroscopic skill efficiency and to demonstrate the use of a surgical checklist for assessing resident surgical efficiency over the course of a surgical rotation. METHODS: Orthopedic surgery residents rotating on the sports medicine service at our institution between 2011 and 2015 were enrolled in this study. Residents were administered a shoulder and knee arthroscopy assessment tool at the beginning and end of their 6-week rotation. The assessment tools consisted of checklist items for knee and shoulder arthroscopy skills. Residents were timed while performing these checklist tasks. The primary outcome measure was resident improvement as a function of time to completion for the checklist items, and the intervention was participation in a 6-week resident rotation with weekly arthroscopy didactics, cadaver simulator work, and operating room experience. A paired t test was used to compare means. RESULTS: Mean time to checklist completion during week 1 among study participants for the knee checklist was 787.4 seconds for the knee checklist and 484.4 seconds at the end of the rotation. Mean time to checklist completion during week 1 among study participants for the shoulder checklist was 1655.3 seconds and 832.7 seconds for the shoulder checklist at the end of the rotation. Mean improvement in time to completion was 303 seconds (p = 0.0006, SD = 209s) and 822.6 seconds (p = 0.00008, SD = 525.2s) for the arthroscopic knee and shoulder assessments, respectively. CONCLUSIONS: An arthroscopic checklist is 1 method to evaluate and assess resident efficiency and improvement during surgical training. Among residents participating in this study, we found statistically significant improvements in time for arthroscopic task completion. LEVEL OF EVIDENCE: II. PMID- 27561629 TI - Temporal Patterns in Fine Particulate Matter Time Series in Beijing: A Calendar View. AB - Extremely high fine particulate matter (PM2.5) concentration has become synonymous to Beijing, the capital of China, posing critical challenges to its sustainable development and leading to major public health concerns. In order to formulate mitigation measures and policies, knowledge on PM2.5 variation patterns should be obtained. While previous studies are limited either because of availability of data, or because of problematic a priori assumptions that PM2.5 concentration follows subjective seasonal, monthly, or weekly patterns, our study aims to reveal the data on a daily basis through visualization rather than imposing subjective periodic patterns upon the data. To achieve this, we conduct two time-series cluster analyses on full-year PM2.5 data in Beijing in 2014, and provide an innovative calendar visualization of PM2.5 measurements throughout the year. Insights from the analysis on temporal variation of PM2.5 concentration show that there are three diurnal patterns and no weekly patterns; seasonal patterns exist but they do not follow a strict temporal division. These findings advance current understanding on temporal patterns in PM2.5 data and offer a different perspective which can help with policy formulation on PM2.5 mitigation. PMID- 27561630 TI - Social selection is a powerful explanation for prosociality. AB - Cultural group selection helps explain human cooperation, but social selection offers a complementary, more powerful explanation. Just as sexual selection shapes extreme traits that increase matings, social selection shapes extreme traits that make individuals preferred social partners. Self-interested partner choices create strong and possibly runaway selection for prosocial traits, without requiring group selection, kin selection, or reciprocity. PMID- 27561631 TI - Efficient synthesis and antioxidant activities of N-heterocyclyl substituted Coenzyme Q analogues. AB - A new strategy for the efficient synthesis of C-5 heterocyclyl substituted Coenzyme Q analogues was developed by N-alkylation of bromomethylated quinone 11 with a series of amines 12 under metal-free conditions. In vitro antioxidant activities of these Coenzyme Q analogues were evaluated and compared with commercial antioxidant Coenzyme Q10 by employing DPPH assay. All these N heterocyclyl substituted Coenzyme Q analogues are found to be exhibiting good antioxidant properties and may be used as potent antioxidants for combating oxidative stress. PMID- 27561632 TI - Delayed Imaging Presentation of a Symptomatic Insulinoma After Bariatric Surgery. AB - Many reports exist on hyperinsulinemic hypoglycemia after bariatric surgery, which can result in persistence of the metabolic syndrome in patients who have undergone these procedures. While the noninsulinoma pancreatogenous hypoglycemia syndrome, or nesidioblastosis, has garnered increased attention in these patients, its presentation is similar to patients with an insulinoma and this entity must therefore be evaluated and ruled out. Herein, we present a patient who developed symptoms of hypoglycemia 7 years after Roux-en-Y gastric bypass surgery. While a diagnosis of insulinoma was entertained, his laboratory values were indeterminate and imaging localization was inconclusive. Because of significant medical comorbidities, he was managed symptomatically until imaging ultimately localized a lesion in the pancreatic uncinate process consistent with an insulinoma. He subsequently underwent resection and remains disease and symptom free 1 year after surgery. This case demonstrates the diagnostic and imaging dilemma in patients with hypoglycemia after bariatric surgery and should be of interest to anyone who cares for these patients. PMID- 27561633 TI - Esophagectomy Following Endoscopic Resection of Submucosal Esophageal Cancer: a Highly Curative Procedure Even with Nodal Metastases. AB - BACKGROUND: Despite the increased risk for nodal disease, definitive endoscopic resection is being increasingly offered for lesions invasive into the submucosa based on the success with intramucosal tumors. The aim of this study was to evaluate survival after esophagectomy alone for confirmed submucosal tumors after endoscopic resection. METHODS: Patients from seven centers in the USA who underwent esophagectomy for submucosal tumors removed with endoscopic resection were analyzed. Nodal involvement was correlated with recurrence and survival. RESULTS: We identified 23 patients with submucosal esophageal adenocarcinoma. Esophagectomy was performed at a median of 2 months (Interquartile range 1-3) after the endoscopic resection. There was no postoperative mortality. Positive nodal disease was seen in 26 % of patients on final pathology. At a median of 37 months (Interquartile range 25-55), 91 % of patients were alive and free of disease. The disease-specific 5-year survival was 88 %. Disease-specific 5-year survival was 67 % in patients with positive nodal metastases and 100 % in those without (p = 0.159). CONCLUSIONS: Esophagectomy is curative in the majority of patients with submucosal tumors even in the presence of nodal metastases. These data serve as a benchmark for comparison when considering extending the indications for therapeutic endoscopic resection for submucosal tumors in the future. PMID- 27561634 TI - Sponge Sampling with Fluorescent In Situ Hybridization as a Screening Tool for the Early Detection of Esophageal Cancer. AB - INTRODUCTION: Sponge cytology is a novel screening tool for esophageal cancer but has been unable to be validated for widespread use. Our aim was to apply fluorescent in situ hybridization to sponge cytology samples in order to evaluate the safety and efficacy of this modality in screening for esophageal cancer. MATERIALS AND METHODS: At a single, multidisciplinary, NCI-designated cancer center, patients completed sponge cytology sampling prior to upper endoscopy. Samples were analyzed by p53 fluorescent in situ hybridization, and results were compared to the endoscopic diagnosis. RESULTS: Fifty patients were enrolled (96 % Caucasian, 68 % male, median age of 67). All patients successfully swallowed the capsule. No complications (string breakage, bleeding, mucosal injury) occurred. Endoscopy revealed that 38 % had normal esophageal mucosa and 62 % had an esophageal mucosal abnormality. In total, six samples demonstrated p53 loss (94 % specificity for any abnormality). The sensitivity of the p53 fluorescent in situ hybridization probe was13.3 % for any abnormality, 10 % for intestinal metaplasia, and 0 % for dysplasia or esophageal cancer. DISCUSSION: Esophageal sponge cytology is a promising, safe, and tolerable method for collecting esophageal cell samples. However, our data suggest that p53 fluorescent in situ hybridization does not improve the sensitivity for detecting cancer in these samples. PMID- 27561635 TI - A Step-Wise Approach to Total Laparoscopic Gastrectomy with Jejunal Pouch Reconstruction: How and Why We Do It. AB - Laparoscopic gastrectomy (LG) is a safe alternative compared to open gastrectomy for cancer. To increase the uptake of minimally invasive approaches and facilitate their analysis and improvement a stepwise approach is warranted. This study describes our technique and experiences total laparoscopic gastrectomy (TLG) with jejunal pouch reconstruction for gastric cancer. Technical modifications throughout the years were described. In patients with anastomotic leakage, the CT-scan and reoperation report were reviewed to identify the location and cause of the leak. A total of 47 patients who underwent laparoscopic total gastrectomy with extracorporeal jejunal pouch reconstruction and stapled circular esophagojejunostomy from May 2007 to August 2015 were prospectively analyzed. A stepwise approach of 10 steps was designed based on video and case analysis. Median operation time was 301 (148-454) minutes and median blood loss was 300 (30-900) milliliters. Anastomotic leakage occurred in six (12.8 %) patients; additionally, one (2.12 %) jejunal-pouch staple line leak was identified. An important modification in our technique was a purse-string suture around the anvil of the circular stapler to prevent esophageal mucosa to slip away. After this modification, the leakage rate was reduced to 7 % in the last 15 procedures. In conclusion, TLG with jejunal pouch reconstruction is a feasible procedure in a selected group of patients. Our stepwise approach and technique may help surgeons to introduce jejunal pouch reconstruction during laparoscopic gastrectomy in their center. PMID- 27561637 TI - Extending the Limits of Resection for Colorectal Liver Metastases ENHANCED ONE STAGE SURGERY. PMID- 27561636 TI - Characterizing Short-Term Outcomes Following Surgery for Rectal Cancer: the Role of Race and Insurance Status. AB - BACKGROUND: There is a paucity of data demonstrating the effect race and insurance status have on postoperative outcomes for patients with rectal cancer. We evaluated factors impacting short-term outcomes following rectal cancer surgery. DESIGN: Patients who underwent surgery for rectal cancer using the University Health System Consortium database from 2011 to 2012 were studied. Univariate and multivariable analyses were used to identify patient related risk factors for 30-day outcomes after proctectomy: complication rate, 30-day readmission, ICU stay, and length of hospital stay (LOS). RESULTS: A total of 9272 proctectomies were identified in this cohort. After adjustment for potential confounders, black patients were more likely to have 30-day readmissions (OR 1.51, 95 % CI 1.26-1.81), ICU stays (OR 1.25, 95 % CI 1.03-1.51), and longer LOS (+1.67 days, 95 % CI 1.21-2.13) when compared to whites. Compared to those with private insurance, patients with public or military insurance or who were self pay had a higher likelihood of having postoperative complications. CONCLUSIONS: In patients who undergo elective proctectomy for rectal cancer, non-white and non privately insured status are associated with significantly worse short-term outcomes. Further studies are needed to determine the implications with respect to receipt of adjuvant therapy and survival. PMID- 27561638 TI - Comparison of a pediatric-inspired treatment protocol versus standard-intensity chemotherapy for young adults with standard-risk BCR-ABL negative acute lymphoblastic leukemia. AB - We investigated the utility of a pediatric-inspired protocol in adults aged 18-40 years with standard-risk BCR-ABL negative acute lymphoblastic leukemia (ALL). Retrospective outcomes of 25 patients treated with a pediatric protocol between 2008 and 2014 were compared with 22 similarly aged patients treated with an adult protocol between 2003 and 2008. Twenty-five (100%) and 19 (86%) patients achieved complete remission, respectively. At median follow-up of 36.8 months, 3-year event-free survival was increased in patients on the pediatric protocol at 80% versus 45% (p = .019). There was a trend toward improved overall survival at 80% versus 59% (p = .12). Treatment-related toxicity was not increased despite the increased treatment intensity. Patients with BCR and/or ABL copy number variation demonstrated comparatively poorer outcomes in both cohorts. In our experience with this cohort of patients, pediatric-based protocols are safe and effective, justifying their use in younger adults with ALL. PMID- 27561639 TI - Exploring the Applicability of Nano-Poration for Remote Control in Smart Drug Delivery Systems. AB - Smart drug delivery systems represent an interesting tool to significantly improve the efficiency and the precision in the treatment of a broad category of diseases. In this context, a drug delivery mediated by nanosecond pulsed electric fields seems a promising technique, allowing for a controlled release and uptake of drugs by the synergy between the electropulsation and nanocarriers with encapsulated drugs. The main concern about the use of electroporation for drug delivery applications is the difference in dimension between the liposome (nanometer range) and the cell (micrometer range). The choice of liposome dimension is not trivial. Liposomes larger than 500 nm of diameter could be recognized as pathogen agents by the immune system, while liposomes of smaller size would require external electric field of high amplitudes for the membrane electroporation that could compromise the cell viability. The aim of this work is to theoretically study the possibility of a simultaneous cell and liposomes electroporation. The numerical simulations reported the possibility to electroporate the cell and a significant percentage of liposomes with comparable values of external electric field, when a 12 nsPEF is used. PMID- 27561640 TI - Perioperative inflammatory response in major fracture: do geriatric patients behave differently? AB - PURPOSE: Interleukin-6 is a mainly proinflammatory interleukin and an indicator for the magnitude of surgery. The IL-6 serum concentration correlates with injury severity, the extent of tissue trauma and has negative impact on prognosis. To date it is unclear whether the immunologic changes assessed are age dependent. The aim of this study is to compare the surgical inflammatory response in different age groups. METHODS: Data were collected at a level-1 university trauma center in a prospective, consecutive cohort study. IL-6 levels were analyzed via ELISA from venous blood samples of cohorts of injuries with typical peak incidence: patients with unstable fractures of the spine (SP) for a middle-aged group and patients with fractures of the proximal femur (PF) for a geriatric group. Surgical treatment was performed using minimal-invasive instrumentation. RESULTS: 25 patients in group SP (age: 51 years +/- 20) and 16 patients in the group PF (age: 73 years +/- 16) were analysed. Group PF showed higher baseline IL 6 concentrations. Surgical treatment was followed by a significant increase of IL 6 levels in both groups 4 and 24 h postoperatively. Concentration profiles were similar, but increase was significantly higher in the PF group 4 h after surgery. CONCLUSION: Both the operative treatment of fractures in a middle-aged (SP) and a geriatric group (PF) lead to significant increasing of IL-6 levels. In view of a comparative surgical burden, these data suggest that age may be a confounding factor for a surgery induced pro-inflammatory response in the early postoperative stage. PMID- 27561644 TI - Low Temperature Solution-Processed Sb:SnO2 Nanocrystals for Efficient Planar Perovskite Solar Cells. AB - Inorganic metal oxide electron-transport layers (ETLs) have the potential to yield perovskite solar cells with improved stability, but generally need high temperature to form conductive and defect-less forms, which is not compatible with the fabrication of flexible and tandem solar cells. Here, we demonstrate a facile strategy for developing efficient inorganic ETLs by doping SnO2 nanocrystals (NCs) with a small amount of Sb using a low-temperature solution processed method. The electrical conductivity was remarkably enhanced by Sb doping, which increased the carrier concentration in Sb:SnO2 NCs. Moreover, the upward shift of the Fermi level owing to doping results in improved energy level alignment, which led to reduced charge recombination, and thus longer electron recombination lifetime and improved open-circuit voltage (VOC ). Therefore, Sb doping of SnO2 significantly enhanced the photovoltaic performance of planar perovskite devices by increasing the fill factor and VOC , and reducing photocurrent hysteresis, extending the potential application of low-temperature processed ETLs in future flexible and tandem solar cells. PMID- 27561646 TI - Sonochemical Assisted Solvothermal Synthesis of Gallium Oxynitride Nanosheets and their Solar-Driven Photoelectrochemical Water-Splitting Applications. AB - Gallium oxynitride (GaON) nanosheets for photoelectrochemical (PEC) analysis are synthesized via direct solvothermal approach. Their FE-SEM revealed nanosheets morphology of GaON prepared at a reaction time of 24 hours at 180 degrees C. The elemental composition and mapping of Ga, O and N are carried out through electron dispersive X-ray spectroscopy (EDX). The cubic structure of GaON nanosheets is elucidated by X-ray diffraction (XRD)analysis. The X-ray Photoelectron Spectroscopy (XPS) further confirms Ga, O and N in their respective ratios and states. The optical properties of GaON nanosheets are evaluated via UV-Visible, Photoluminescence (PL) and Raman spectroscopy's. The band gap energy of ~1.9 eV is calculated from both absorption and diffused reflectance spectroscopy's which showed stronger p-d repulsions in the Ga (3d) and N (2p) orbitals. This effect and chemical nitridation caused upward shift of valence band and band gap reduction. The GaON nanosheets are investigated for PEC studies in a standard three electrode system under 1 Sun irradiation in 0.5 M Na2SO4. The photocurrent generation, oxidation and reduction reactions during the measurements are observed by Chronoampereometry, linear sweep Voltametry (LSV) and Cyclic Voltametry (CV) respectively. Henceforward, these GaON nanosheets can be used as potential photocatalyts for solar water splitting. PMID- 27561647 TI - Frozen cultural plasticity. AB - We discuss cultural group selection under the view of the frozen plasticity theory and the different explanatory power and predictions of this framework. We present evidence that cultural adaptations and their influence on the degree of cooperation may be more complex than presented by Richerson et al., and conclude with the gene-environment-culture relationship and its impacts on cultural group selection. PMID- 27561645 TI - Discovery of New Benzothiazine Derivative as Modulator of Pro- and Anti inflammatory Cytokines in Rheumatoid Arthritis. AB - The anti-inflammatory activities of benzothiazine and pyrazole derivatives are well documented. A series of novel N'-arylmethylidene-2-(3,4-dimethyl-5,5 dioxidopyrazolo(4,3 c)(1,2) benzothiazin-2(4H)yl) acetohydrazide compounds were previously synthesized by combining benzothiazine and pyrazole moieties into a single nucleus. The current study investigates the anti-arthritic potential of 3 ethoxy-4-hydroxyphenyl derivative (EHP) and its possible mechanism in arthritic rat model. Sprague-Dawley rats were induced rheumatoid arthritis with Freund's complete adjuvant and treated with EHP and piroxicam. At the end of the study, arthritic score was calculated, and ankle joint histopathology was performed using hematoxylin and eosin staining. Real-time reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine mRNA expression and protein levels of various inflammatory markers, respectively. In vitro concanavalin A (ConA)-stimulated splenocyte proliferation was measured. Serum levels of C-reactive protein (CRP), urea, creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were also determined. EHP significantly attenuated macroscopic arthritic score, joint histopathological lesions, and CRP levels. Treatment with EHP significantly reduced pro-inflammatory tissue necrosis factor-alpha (TNF alpha), nuclear factor-kappa B (NF-kB), interleukin-17 (IL-17), and prostaglandin E2 (PGE2) levels and increased the levels of anti-inflammatory interleukin-4 (IL 4) and interleukin-10 (IL-10). ConA-stimulated splenocyte proliferation was also significantly suppressed by treatment with EHP. Normalizing all hematological markers and ALP levels, EHP did not display any sign of nephrotoxicity and hepatotoxicity as determined by urea, creatinine, ALT, and AST levels. In conclusion, EHP possesses significant anti-arthritic property which may be attributed to its anti-inflammatory and immunomodulatory effects. PMID- 27561648 TI - The pharmacoepigenetics of drug metabolism and transport in breast cancer: review of the literature and in silico analysis. AB - The focus of this manuscript is on DNA methylation and miRNA regulation of drug metabolizing enzymes and drug transporters involved in the disposition of drugs commonly used in breast cancer. We start with a review of the available scant literature and follow with an in silico analysis of the CpG islands and miRNA binding sites of genes of interest. We make the case that there is room for further research to include more genes and miRNAs despite the extensive sharing of miRNA targets by candidate genes of interest. We also stress on the role of peripheral blood as a source of pharmacoepigenetic biomarkers, and point out the lack of toxicoepigenetic studies in breast cancer. PMID- 27561649 TI - Quantify patient-specific coronary material property and its impact on stress/strain calculations using in vivo IVUS data and 3D FSI models: a pilot study. AB - Computational models have been used to calculate plaque stress and strain for plaque progression and rupture investigations. An intravascular ultrasound (IVUS) based modeling approach is proposed to quantify in vivo vessel material properties for more accurate stress/strain calculations. In vivo Cine IVUS and VH IVUS coronary plaque data were acquired from one patient with informed consent obtained. Cine IVUS data and 3D thin-slice models with axial stretch were used to determine patient-specific vessel material properties. Twenty full 3D fluid structure interaction models with ex vivo and in vivo material properties and various axial and circumferential shrink combinations were constructed to investigate the material stiffness impact on stress/strain calculations. The approximate circumferential Young's modulus over stretch ratio interval [1.0, 1.1] for an ex vivo human plaque sample and two slices (S6 and S18) from our IVUS data were 1631, 641, and 346 kPa, respectively. Average lumen stress/strain values from models using ex vivo, S6 and S18 materials with 5 % axial shrink and proper circumferential shrink were 72.76, 81.37, 101.84 kPa and 0.0668, 0.1046, and 0.1489, respectively. The average cap strain values from S18 material models were 150-180 % higher than those from the ex vivo material models. The corresponding percentages for the average cap stress values were 50-75 %. Dropping axial and circumferential shrink consideration led to stress and strain over-estimations. In vivo vessel material properties may be considerably softer than those from ex vivo data. Material stiffness variations may cause 50-75 % stress and 150-180 % strain variations. PMID- 27561650 TI - Material model of pelvic bone based on modal analysis: a study on the composite bone. AB - Digital models based on finite element (FE) analysis are widely used in orthopaedics to predict the stress or strain in the bone due to bone-implant interaction. The usability of the model depends strongly on the bone material description. The material model that is most commonly used is based on a constant Young's modulus or on the apparent density of bone obtained from computer tomography (CT) data. The Young's modulus of bone is described in many experimental works with large variations in the results. The concept of measuring and validating the material model of the pelvic bone based on modal analysis is introduced in this pilot study. The modal frequencies, damping, and shapes of the composite bone were measured precisely by an impact hammer at 239 points. An FE model was built using the data pertaining to the geometry and apparent density obtained from the CT of the composite bone. The isotropic homogeneous Young's modulus and Poisson's ratio of the cortical and trabecular bone were estimated from the optimisation procedure including Gaussian statistical properties. The performance of the updated model was investigated through the sensitivity analysis of the natural frequencies with respect to the material parameters. The maximal error between the numerical and experimental natural frequencies of the bone reached 1.74 % in the first modal shape. Finally, the optimised parameters were matched with the data sheets of the composite bone. The maximal difference between the calibrated material properties and that obtained from the data sheet was 34 %. The optimisation scheme of the FE model based on the modal analysis data provides extremely useful calibration of the FE models with the uncertainty bounds and without the influence of the boundary conditions. PMID- 27561651 TI - The effect of temperature and bacterial growth phase on protein extraction by means of electroporation. AB - Different chemical and physical methods are used for extraction of proteins from bacteria, which are used in variety of fields. But on a large scale, many methods have severe drawbacks. Recently, extraction by means of electroporation showed a great potential to quickly obtain proteins from bacteria. Since many parameters are affecting the yield of extracted proteins, our aim was to investigate the effect of temperature and bacterial growth phase on the yield of extracted proteins. At the same time bacterial viability was tested. Our results showed that the temperature has a great effect on protein extraction, the best temperature post treatment being 4 degrees C. No effect on bacterial viability was observed for all temperatures tested. Also bacterial growth phase did not affect the yield of extracted proteins or bacterial viability. Nevertheless, further experiments may need to be performed to confirm this observation, since only one incubation temperature (4 degrees C) and one incubation time before and after electroporation (0.5 and 1h) were tested for bacterial growth phase. Based on our results we conclude that temperature is a key element for bacterial membrane to stay in a permeabilized state, so more proteins flow out of bacteria into surrounding media. PMID- 27561652 TI - Synthesis and Characterization of Self-Standing and Highly Flexible delta MnO2@CNTs/CNTs Composite Films for Direct Use of Supercapacitor Electrodes. AB - Self-standing and flexible films worked as pseudocapacitor electrodes have been fabricated via a simple vacuum-filtration procedure to stack delta-MnO2@carbon nanotubes (CNTs) composite layer and pure CNT layer one by one with CNT layers ended. The lightweight CNTs layers served as both current collector and supporter, while the MnO2@CNTs composite layers with birnessite-type MnO2 worked as active layer and made the main contribution to the capacitance. At a low discharge current of 0.2 A g(-1), the layered films displayed a high areal capacitance of 0.293 F cm(-2) with a mass of 1.97 mg cm(-2) (specific capacitance of 149 F g(-1)) and thickness of only 16.5 MUm, and hence an volumetric capacitance of about 177.5 F cm(-3). Moreover, the films also exhibited a good rate capability (only about 15% fading for the capacitance when the discharge current increased to 5 A g(-1) from 0.2 A g(-1)), outstanding cycling stability (about 90% of the initial capacitance was remained after 5,000 cycles) and high flexibility (almost no performance change when bended to different angles). In addition, the capacitance of the films increased proportionally with the stacked layers and the geometry area. E.g., when the stacked layers were three times many with a mass of 6.18 mg cm(-2), the areal capacitance of the films was increased to 0.764 F cm(-2) at 0.5 A g(-1), indicating a high electronic conductivity. It is not overstated to say that the flexible and lightweight layered films emerged high potential for future practical applications as supercapacitor electrodes. PMID- 27561653 TI - Acute Ischemic Stroke Severity, Progression, and Outcome Relate to Changes in Dipeptidyl Peptidase IV and Fibroblast Activation Protein Activity. AB - Dipeptidyl peptidase IV (DPPIV) inhibition may be a promising therapeutic strategy for acute stroke treatment, given its potential to prolong the biological half-life of neuroprotective substrates. A related protease, fibroblast activation protein (FAP), was recently shown to inactivate the same substrates. Therefore, it should also be investigated as a potential target in stroke. The study aimed to investigate whether stroke severity and outcome correlate with DPPIV and FAP activities and their kinetics shortly after acute ischemic stroke. DPPIV and FAP activities were analyzed in the serum of 50 hyperacute stroke patients at admission, 1 day, 3 days, and 7 days after stroke onset and in 50 age-matched healthy controls. This was done as part of the Middelheim's Interdisciplinary Stroke Study. DPPIV activity tended to increase shortly after stroke compared to the control population. DPPIV and FAP activities steadily decreased in the first week after stroke onset. Higher infarct volumes (>=5 ml) and a more severe stroke (NIHSS >7) at admission were correlated with a stronger decrease in the activities of both enzymes. Moreover, these patients more often developed a progressive stroke, were more often institutionalized. Patients with a stronger increase in DPPIV activity at admission and decrease in the activity of both DPPIV and FAP during the first week after stroke onset had a more severe stroke and worse short-term outcomes. PMID- 27561654 TI - Accurate Morphology Preserving Segmentation of Overlapping Cells based on Active Contours. AB - The identification of fluorescently stained cell nuclei is the basis of cell detection, segmentation, and feature extraction in high content microscopy experiments. The nuclear morphology of single cells is also one of the essential indicators of phenotypic variation. However, the cells used in experiments can lose their contact inhibition, and can therefore pile up on top of each other, making the detection of single cells extremely challenging using current segmentation methods. The model we present here can detect cell nuclei and their morphology even in high-confluency cell cultures with many overlapping cell nuclei. We combine the "gas of near circles" active contour model, which favors circular shapes but allows slight variations around them, with a new data model. This captures a common property of many microscopic imaging techniques: the intensities from superposed nuclei are additive, so that two overlapping nuclei, for example, have a total intensity that is approximately double the intensity of a single nucleus. We demonstrate the power of our method on microscopic images of cells, comparing the results with those obtained from a widely used approach, and with manual image segmentations by experts. PMID- 27561655 TI - Social insects, merely a "fun house" mirror of human social evolution. AB - Social insects show us very little about the evolution of complex human society. As more relevant literature demonstrates, ultrasociality is a cause rather than an effect of human social evolution. PMID- 27561656 TI - Why a developmental perspective is critical for understanding human cognition. AB - The evidence that Anderson (2014) marshals in support of his theory of neural reuse is persuasive. However, his theoretical framework currently lacks a developmental dimension. We argue that an account of the fundamental aspects of developmental change, as well as the temporal context within which change occurs, would greatly enhance Anderson's theory. PMID- 27561657 TI - Antithyroid drugs during breastfeeding. AB - Antithyroid drugs (ATDs) are widely used for the treatment of Graves' disease (GD) in the general population. Over the past decade, there has been an increasing awareness that several disturbances of thyroid function may occur in mothers after delivery which may be more prevalent than previously appreciated. Exacerbation of immune reactions occurs 3-12 month following delivery. Management of hyperthyroidism during lactation requires special considerations and should be implemented to prevent any adverse outcomes in mother and neonate. Continuation of breastfeeding is safe and should be encouraged in hyperthyroid mothers taking ATDs, whether these are ATDs being continued after gestation or indeed ATD treatment initiated in the postpartum period. Given PTU hepatotoxicity concerns, experts currently recommend using low-to-moderate MMI doses as a first-line therapy in lactating mothers. PTU should be reserved only as a second-line agent for cases of severe hyperthyroidism (thyroid storm) and allergic reactions to previous MMI treatment. ATD should be administered in divided doses immediately following each feeding. Evaluation of thyroid function tests is advisable at least 3-4 weeks after the initiation of breastfeeding. PMID- 27561658 TI - Prevalence and consequence of subacute ruminal acidosis in Polish dairy herds. AB - The aim of this study was to estimate the prevalence of subacute ruminal acidosis (SARA) in Polish high-yielding dairy herds. Also, the relationships between the chemical composition of the diet and the feed particle size, ruminal pH and the occurrence of this metabolic disease and the fermentation profile were determined. Rumen fluid samples were obtained from a total of 213 cows from nine dairy herds (>=20 cows per herd) via rumenocentesis. Almost 14% (30/213) of cows as acidotic (pH<5.6) were found, which is indicative of SARA. Moreover, 44% of the herds were classified as SARA-positive and 56% as SARA-negative. Results of the current study suggested that the physically effective NDF (NDF>1.18 mm) -to starch ratio could be better indices than peNDF>1.18 mm to preventing the occurrence of SARA, and their level should not be lower than 1.00. Also, linear negative relationships between rumen fluid pH and concentration of propionate, valerate and total VFA were determined. According to the herd's SARA status and rumen fluid biochemical indices, there were significant differences between the pH of rumen fluid (p <= 0.01), concentrations of acetate (p <= 0.05), propionate (p <= 0.05), n-butyrate (p <= 0.01), n-valerate (p <= 0.01), the sum of VFA (p <= 0.01) and ammonia (p <= 0.05) in SARA-positive herds compared to SARA-negative herds. The better understanding the strategy of ruminant nutrition to coordinate energy conversion and the role of the ruminal pH in regulating N-NH3 production, absorption through rumen mucosa, urea secretion, the more successfully we can utilize these processes with due recognition of animal needs and welfare, as well as prevention of SARA occurrence. PMID- 27561659 TI - Kinase inhibitor pharmacokinetics: comprehensive summary and roadmap for addressing inter-individual variability in exposure. AB - INTRODUCTION: Small molecule protein kinase inhibitors (KIs) are a class of drugs with complex and unconventional physiochemical and pharmacokinetic characteristics. Cytochrome P450 mediated metabolism and transporter-mediated uptake and efflux are important processes that determine KI disposition and exposure. Areas covered: We provide an overview of KI pharmacology, with a comprehensive summary of KI physiochemical and pharmacokinetic properties and description of the major sources of variability in KI pharmacokinetics focusing on common pathways involved in determining exposure. We also consider the strategies proposed to optimize KI dosing, appraise the current evidence for their use and analyze the challenges and knowledge gaps for KI dose optimization. Expert opinion: A number of strategies to optimize KI dosing have been proposed, but evidence underpinning their use is limited. The major challenge for optimized KI dosing is the development of high-quality evidence to demonstrate a significant improvement in therapeutic outcomes and /or reduction in adverse events through appropriately designed trials in a setting where the limited KI prescribing restricts capacity to undertake prospective randomized studies. If precision KI dosing can facilitate a fraction of the reported observational benefits, then substantial gains in patient outcomes will be derived in a cost effective manner. PMID- 27561660 TI - Essential oil of Kurzamra pulchella (Clos) Kuntze (Lamiaceae, Nepetoideae, Mentheae, Menthinae): relationship with chemotype groups in the subtribe Menthinae. AB - The chemical composition of the essential oil of Kurzamra pulchella (Lamiaceae) was determined. Twelve compounds were identified, with isomenthone (60.6%) and pulegone (37.1%) predominating. Chemotaxonomical considerations were discussed. PMID- 27561661 TI - Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis - a systematic review and meta-analysis. AB - OBJECTIVES: Since the peptidyl arginine deiminase of Porphyromonas gingivalis is able to citrullinate peptides and proteins, various studies have suggested the species as a possible link between periodontal disease (PD) and rheumatoid arthritis (RA). This systematic review including meta-analysis was aimed to evaluate whether differences in terms of antibody titers against P. gingivalis exist between RA patients and systemically healthy individuals with and without PD. MATERIALS AND METHODS: The following focused question was addressed: Are the antibody titers against P. gingivalis of RA patients different from systemically healthy individuals with and without PD? A systematic data search was conducted in MEDLINE and EMBASE. The collected data underwent a meta-analysis to detect statistically significant differences in terms of antibody levels between the groups. RESULTS: From 114 articles found by the search 13 articles met the inclusion criteria and provided data suitable for meta-analysis. After analyzing various levels of confinement the meta-analysis revealed a statistically significant higher antibody titer against P. gingivalis in patients suffering from RA in comparison with systemically and periodontally healthy controls (p < 0.01) and systemically healthy patients with PD (p < 0.01). CONCLUSION: The present findings indicate that RA is often accompanied by the presence of an immune response against P. gingivalis. CLINICAL RELEVANCE: The significantly higher antibody response to P. gingivalis in comparison to systemically healthy individuals supports the link between PD and RA by P. gingivalis. Screening of the regularly taken blood samples of RA patients for P. gingivalis antibodies may help to sensitize rheumatologists and RA patients for improving periodontal health. PMID- 27561663 TI - CD26 and Asthma: a Comprehensive Review. AB - Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy. PMID- 27561664 TI - Manipulating Sensory and Phytochemical Profiles of Greenhouse Tomatoes Using Environmentally Relevant Doses of Ultraviolet Radiation. AB - Fruits harvested from off-season, greenhouse-grown tomato plants have a poor reputation compared to their in-season, garden-grown counterparts. Presently, there is a gap in knowledge with regard to the role of UV-B radiation (280-315 nm) in determining greenhouse tomato quality. Knowing that UV-B is a powerful elicitor of secondary metabolism and not transmitted through greenhouse glass and some greenhouse plastics, we tested the hypothesis that supplemental UV-B radiation in the greenhouse will impart quality attributes typically associated with garden-grown tomatoes. Environmentally relevant doses of supplemental UV-B radiation did not strongly affect antioxidant compounds of fruits, although the flavonol quercetin-3-O-rutinoside (rutin) significantly increased in response to UV-B. Physicochemical metrics of fruit quality attributes and consumer sensory panels were used to determine if any such differences altered consumer perception of tomato quality. Supplemental UV-A radiation (315-400 nm) pre-harvest treatments enhanced sensory perception of aroma, acidity, and overall approval, suggesting a compelling opportunity to environmentally enhance the flavor of greenhouse-grown tomatoes. The expression of the genes COP1 and HY5 were indicative of adaptation to UV radiation, which explains the lack of marked effects reported in these studies. To our knowledge, these studies represent the first reported use of environmentally relevant doses of UV radiation throughout the reproductive portion of the tomato plant life cycle to positively enhance the sensory and chemical properties of fruits. PMID- 27561665 TI - Establishing Evidence for the Future of Kidney Disease Education. PMID- 27561662 TI - Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): a Review. AB - Chronic traumatic encephalopathy (CTE) is a neuropathologically defined disease reportedly linked to a history of repetitive brain trauma. As such, retired collision sport athletes are likely at heightened risk for developing CTE. Researchers have described distinct pathological features of CTE as well a wide range of clinical symptom presentations, recently termed traumatic encephalopathy syndrome (TES). These clinical symptoms are highly variable, non-specific to individuals described as having CTE pathology in case reports, and are often associated with many other factors. This review describes the cognitive, emotional, and behavioral changes associated with 1) developmental and demographic factors, 2) neurodevelopmental disorders, 3) normal aging, 4) adjusting to retirement, 5) drug and alcohol abuse, 6) surgeries and anesthesia, and 7) sleep difficulties, as well as the relationship between these factors and risk for developing dementia-related neurodegenerative disease. We discuss why some professional athletes may be particularly susceptible to many of these effects and the importance of choosing appropriate controls groups when designing research protocols. We conclude that these factors should be considered as modifiers predominantly of the clinical outcomes associated with repetitive brain trauma within a broader biopsychosocial framework when interpreting and attributing symptom development, though also note potential effects on neuropathological outcomes. Importantly, this could have significant treatment implications for improving quality of life. PMID- 27561667 TI - Patient Education and Choice of Peritoneal Dialysis. PMID- 27561666 TI - Smoking, Vascular Events, and ESRD in Patients With CKD. PMID- 27561668 TI - Quiz Page September 2016: Multiple Myeloma and Hypophosphatemia. PMID- 27561669 TI - Asymmetric cryo-EM reconstruction of phage MS2 reveals genome structure in situ. AB - In single-stranded ribonucleic acid (RNA) viruses, virus capsid assembly and genome packaging are intertwined processes. Using cryo-electron microscopy and single particle analysis we determined the asymmetric virion structure of bacteriophage MS2, which includes 178 copies of the coat protein, a single copy of the A-protein and the RNA genome. This reveals that in situ, the viral RNA genome can adopt a defined conformation. The RNA forms a branched network of stem loops that almost all allocate near the capsid inner surface, while predominantly binding to coat protein dimers that are located in one-half of the capsid. This suggests that genomic RNA is highly involved in genome packaging and virion assembly. PMID- 27561670 TI - Vibrant Soundbridge(r) in preschool children with unilateral aural atresia: acceptance and benefit. AB - The aim of this pilot study was to determine the acceptance and benefit from the middle ear implant system Vibrant Soundbridge(r) (VSB, MED-EL Corporation, Austria) by means of a questionnaire, compared to a previously used conventional bone conducting hearing device, in preschool children with unilateral congenital aural atresia. Prospective cohort study. All nine children with unilateral congenital aural atresia used the VSB and had previous experience with a bone conducting hearing device. The benefit from the VSB was evaluated by questionnaires concerning acceptance of hearing aids, handling, listening effort, behavior, quality of life, and the duration of daily use and compared to the experience with the bone conducting hearing device. In addition, to quantify the benefit from the VSB use, audiological assessment (pure-tone audiometry via free field testing, speech audiometry, and localization test) was performed with and without VSB. The questionnaires and audiological test results were compared pairwise. According to all questionnaire areas, children benefited significantly more from the VSB compared to bone conducting hearing device (ps <.05). The most important finding was a significant increase in daily use from 2 h for the bone conducting hearing device to 10 h for the VSB. Children performed significantly better with the VSB than without it in the audiological assessment. Children with unilateral aural atresia benefited significantly more from the VSB compared to a conventional bone conducting hearing device according to the parents' questionnaires and yielded better results in the audiometry and localization test with the VSB than without it. PMID- 27561671 TI - Additional non-sentinel lymph node metastases in early oral cancer patients with positive sentinel lymph nodes. AB - To determine risk factors for additional non-sentinel lymph node metastases in neck dissection specimens of patients with early stage oral cancer and a positive sentinel lymph node biopsy (SLNB). A retrospective analysis of 36 previously untreated SLNB positive patients in our institution and investigation of currently available literature of positive SLNB patients in early stage oral cancer was done. Degree of metastatic involvement [classified as isolated tumor cells (ITC), micro- and macrometastasis] of the sentinel lymph node (SLN), the status of other SLNs, and additional non-SLN metastases in neck dissection specimens were analyzed. Of 27 studies, comprising 511 patients with positive SLNs, the pooled prevalence of non-SLN metastasis in patients with positive SLNs was 31 %. Non-SLN metastases were detected (available from 9 studies) in 13, 20, and 40 % of patients with ITC, micro-, and macrometastasis in the SLN, respectively. The probability of non-SLN metastasis seems to be higher in the case of more than one positive SLN (29 vs. 24 %), the absence of negative SLNs (40 vs. 19 %), and a positive SLN ratio of more than 50 % (38 vs. 19 %). Additional non-SLN metastases were found in 31 % of neck dissections following positive SLNB. The presence of multiple positive SLNs, the absence of negative SLNs, and a positive SLN ratio of more than 50 % may be predictive factors for non-SLN metastases. Classification of SLNs into ITC, micro-, and macrometastasis in the future SLNB studies is important to answer the question if treatment of the neck is always needed after positive SLNB. PMID- 27561672 TI - Workforce capacity to address obesity: a Western Australian cross-sectional study identifies the gap between health priority and human resources needed. AB - BACKGROUND: The disease burden due to poor nutrition, physical inactivity and obesity is high and increasing. An adequately sized and skilled workforce is required to respond to this issue. This study describes the public health nutrition and physical activity (NAPA) practice priorities and explores health managers and practitioner's beliefs regarding workforce capacity to deliver on these priorities. METHODS: A workforce audit was conducted including a telephone survey of all managers and a postal survey of practitioners working in the area of NAPA promotion in Western Australia in 2004. Managers gave their perspective on workforce priorities, current competencies and future needs, with a 70 % response rate. Practitioners reported on public health workforce priorities, qualifications and needs, with a 56 % response rate. RESULTS: The top practice priorities for managers were diabetes (35 %), alcohol and other drugs (33 %), and cardiovascular disease (27 %). Obesity (19 %), poor nutrition (15 %) and inadequate physical activity (10 %) were of lower priority. For nutrition, managers identified lack of staff (60.4 %), organisational and management factors (39.5 %) and insufficient financial resources (30.2 %) as the major barriers to adequate service delivery. For physical activity services, insufficient financial resources (41.7 %) and staffing (35.4 %) and a lack of specific physical activity service specifications (25.0 %) were the main barriers. Practitioners identified inadequate staffing as the main barrier to service delivery for nutrition (42.3 %) and physical activity (23.3 %). Ideally, managers said they required 152 % more specialist nutritionists in the workforce and 131 % specialists for physical activity services to meet health outcomes in addition to other generalist staff. CONCLUSION: Human and financial resources and organisational factors were the main barriers to meeting obesity, and public health nutrition and physical activity outcomes. Services were being delivered by generalists rather than specialists, which may reduce service effectiveness. Although conclusions from this research need to take into account the fact that the audit was conducted in 2004, the findings suggest that there was a need to equip health services with an adequately skilled workforce of sufficient capacity to deliver an effective public health response to the obesity epidemic, particularly addressing poor nutrition and physical inactivity. PMID- 27561673 TI - Computational analysis of translational readthrough proteins in Drosophila and yeast reveals parallels to alternative splicing. AB - In translational readthrough (TR) the ribosome continues extending the nascent protein beyond the first in-frame termination codon. Due to the lack of dedicated analyses of eukaryotic TR cases, the associated functional-evolutionary advantages are still unclear. Here, based on a variety of computational methods, we describe the structural and functional properties of previously proposed D. melanogaster and S. cerevisiae TR proteins and extensions. We found that in D. melanogaster TR affects long proteins in mainly regulatory roles. Their TR extensions are structurally disordered and rich in binding motifs, which, together with their cell-type- and developmental stage-dependent inclusion, suggest that similarly to alternatively spliced exons they rewire cellular interaction networks in a temporally and spatially controlled manner. In contrast, yeast TR proteins are rather short and fulfil mainly housekeeping functions, like translation. Yeast extensions usually lack disorder and linear motifs, which precludes elucidating their functional relevance with sufficient confidence. Therefore we propose that by being much more restricted and by lacking clear functional hallmarks in yeast as opposed to fruit fly, TR shows remarkable parallels with alternative splicing. Additionally, the lack of conservation of TR extensions among orthologous TR proteins suggests that TR mediated functions may be generally specific to lower taxonomic levels. PMID- 27561674 TI - Atrial Fibrillation in Transient Ischemic Attack Versus Ischemic Stroke: A Swedish Stroke Register (Riksstroke) Study. AB - BACKGROUND AND PURPOSE: Compared with ischemic stroke (IS), the association of atrial fibrillation (AF) with transient ischemic attack (TIA) is less well established. We aimed to assess the proportion of AF in patients with TIA, and these patients' characteristics and secondary preventive treatment in comparison to patients with IS. METHODS: Hospital-based data on TIA and IS events, registered from July 2011 to June 2013, were obtained from the Swedish Stroke Register (Riksstroke). A time-based TIA definition (duration of symptoms <24 hours) was applied. AF was registered as present when previously known or diagnosed at the time of assessment. RESULTS: AF was present in 2779 of 14 980 (18.6%) patients with TIA and 13 258 of 44 173 (30.0%) patients with IS. The proportion of AF increased with age, reaching 32.9% in TIA and 46.6% in IS patients >=85 years. Both in TIA and IS, age, hypertension, a history of stroke, and TIA, and being a nonsmoker were associated with the presence of AF. In contrast to IS, AF was less common in female than in male patients with TIA. At discharge, 64.2% of TIA and 50.0% of IS patients with AF were treated with oral anticoagulants. Proportions of AF patients treated with oral anticoagulants decreased substantially with increasing age. CONCLUSIONS: AF is highly prevalent not only in IS but also in TIA patients, with proportions steeply increasing with age. In both TIA and IS, a substantial proportion of patients with AF were discharged without anticoagulant therapy. PMID- 27561677 TI - Gene therapy improves dental manifestations in hypophosphatasia model mice. AB - BACKGROUND AND OBJECTIVE: Hypophosphatasia is a rare inherited skeletal disorder characterized by defective bone mineralization and deficiency of tissue non specific alkaline phosphatase (TNSALP) activity. The disease is caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding TNSALP. Early exfoliation of primary teeth owing to disturbed cementum formation, periodontal ligament weakness and alveolar bone resorption are major complications encountered in oral findings, and discovery of early loss of primary teeth in a dental examination often leads to early diagnosis of hypophosphatasia. Although there are no known fundamental treatments or effective dental approaches to prevent early exfoliation of primary teeth in affected patients, several possible treatments have recently been described, including gene therapy. Gene therapy has also been applied to TNSALP knockout mice (Alpl-/- ), which phenocopy the infantile form of hypophosphatasia, and improved their systemic condition. In the present study, we investigated whether gene therapy improved the dental condition of Alpl-/- mice. MATERIAL AND METHODS: Following sublethal irradiation (4 Gy) at the age of 2 d, Alpl-/- mice underwent gene therapy using bone marrow cells transduced with a lentiviral vector expressing a bone-targeted form of TNSALP injected into the jugular vein (n = 3). Wild-type (Alpl+/+ ), heterozygous mice (Alpl+/- ) and Alpl-/- mice were analyzed at 9 d of age (n = 3 of each), while Alpl+/+ mice and treated or untreated Alpl-/- mice were analyzed at 1 mo of age (n = 3 of each), and Alpl+/- mice and Alpl-/- mice with gene therapy were analyzed at 3 mo of age (n = 3 of each). A single mandibular hemi-section obtained at 1 mo of age was analyzed using a small animal computed tomography machine to assess alveolar bone formation. Other mandibular hemi-sections obtained at 9 d, 1 mo and 3 mo of age were subjected to hematoxylin and eosin staining and immunohistochemical analysis of osteopontin, a marker of cementum. RESULTS: Immunohistochemical analysis of osteopontin, a marker of acellular cementum, revealed that Alpl-/- mice displayed impaired formation of cementum and alveolar bone, similar to the human dental phenotype. Cementum formation was clearly present in Alpl-/- mice that underwent gene therapy, but did not recover to the same level as that in wild-type (Alpl+/+ ) mice. Micro computed tomography examination showed that gene therapy improved alveolar bone mineral density in Alpl-/- mice to a similar level to that in Alpl+/+ mice. CONCLUSIONS: Our results suggest that gene therapy can improve the general condition of Alpl-/- mice, and induce significant alveolar bone formation and moderate improvement of cementum formation, which may contribute to inhibition of early spontaneous tooth exfoliation. PMID- 27561676 TI - Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development. AB - Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical beta-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial beta-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation. PMID- 27561678 TI - Effects of panax notoginseng saponins on the osteogenic differentiation of rabbit bone mesenchymal stem cells through TGF-beta1 signaling pathway. AB - BACKGROUND: Panax Notoginseng is a well-known Chinese medicinal herb which has been used in China for treatment of bone fracture for hundreds of years. However, the specific biological mechanisms of osteogenic effect of PNS are not well understood. METHODS: In this study, newborn rabbit BMSCs were isolated, and then identified by the positive expression rates of cell surface markers, including CD29, CD45 and HLA-DR, which were detected by flow cytometry(FCM). After the lentivirus-induced cell model of TGF-beta1 gene silencing was established, the interference efficiency was tested by q-PCR and Western blot, and the growth curve of silencing cells was drawn by MTT so as to grasp the growth rhythm of silencing cells. In the alizarin red-staining experiment, the effect of 100 mg/L PNS on the activity of intracellular ALP of TGF-beta1 gene silencing BMSCs was detected, so as to observe the effect of 100 mg/L PNS on the formation of calcium nodes of gene silencing BMSCs. RESULTS: By separating rabbit BMSCs, the lentivirus-induced cell model of TGF-beta1 gene silencing was established. Both TGF-beta1 mRNA and protein expression were restrained significantly, and the target gene kept silence stably via the verification of q-PCR and Western blot; there was no significant differences of the growth curve between RNAi cells and normal cells; the activity of intracellular APL in 100 mg RNAi group was obviously lower than that in 100 mg group (p < 0.05), but higher than that in the normal group; in the alizarin red-staining experiment, it focused on the effects of PNS on the formation of calcium nodes of gene silencing BMSCs, which showed that calcium nodes could be formed in 100 mg RNAi group but its quantity was lower than that of 100 mg group (p < 0.05). CONCLUSIONS: It was shown that silencing TGF-beta1 gene could interrupt the osteogenic effects of PNS. PNS may have a promoting effect on osteogenic differentiation of rabbits' BMSCs in vitro by up-regulating the gene expression of TGF-beta1. PMID- 27561679 TI - Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester. AB - SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/mL) with or without resveratrol (10 MUM) for 24 h. The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA), androstenedione and 11 deoxicortisol by ACTH-activated and unstimulated HFAC, which was associated with inhibition of the activities and expression of cytochromes 17alpha hydroxylase/17,20 lyase (CYP17) and 21-hydroxylase (CYP21) in these fetal adrenocortical cells. CONCLUSION: Our in vitro findings on the sensitivity of human fetal adrenal steroidogenesis to resveratrol at GW9-12 suggest that intake of this polyphenol at high doses by women who are at early stages of pregnancy is undesirable. PMID- 27561681 TI - Rugose atypical Vibrio cholerae O1 El Tor responsible for 2009 cholera outbreak in India. AB - Vibrio cholerae causes cholera outbreaks in endemic regions where the water quality and sanitation facilities remain poor. Apart from biotype and serotype changes, V. cholerae undergoes phase variation, which results in the generation of two morphologically different variants termed smooth and rugose. In this study, 12 rugose (R-VC) and 6 smooth (S-VC) V. cholerae O1 Ogawa isolates were identified in a cholera outbreak that occurred in Hyderabad, India. Antimicrobial susceptibility results showed that all the isolates were resistant to ampicillin, furazolidone and nalidixic acid. In addition, R-VC isolates were resistant to ciprofloxacin (92 %), streptomycin (92 %), erythromycin (83 %), trimethoprim sulfamethoxazole (75 %) and tetracycline (75 %). Based on the ctxB gene analysis, all the isolates were identified as El Tor variant with mutation in two positions of ctxB, similar to the classical biotype. The R-VC isolates specifically showed excessive biofilm formation and were comparatively less motile. In addition, the majority of these isolates (~83 %) displayed random mutations in the hapR gene, which encodes haemagglutinin protease regulatory protein. In the PFGE analysis, R VC and S-VC were placed in distinct clusters but remained clonally related. In the ribotyping analysis, all the R-VC isolates exhibited R-III pattern, which is a prevailing type among the current El Tor isolates. A hapR deletion mutant generated using an S-VC isolate expressed rugose phenotype. To our knowledge, this is the first report on the association of rugose V. cholerae O1 in a large cholera outbreak with extended antimicrobial resistance and random mutations in the haemagglutinin protease regulatory protein encoding gene (hapR). PMID- 27561680 TI - VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington's disease. AB - Mutant Huntingtin (mtHtt) causes neurodegeneration in Huntington's disease (HD) by evoking defects in the mitochondria, but the underlying mechanisms remains elusive. Our proteomic analysis identifies valosin-containing protein (VCP) as an mtHtt-binding protein on the mitochondria. Here we show that VCP is selectively translocated to the mitochondria, where it is bound to mtHtt in various HD models. Mitochondria-accumulated VCP elicits excessive mitophagy, causing neuronal cell death. Blocking mtHtt/VCP mitochondrial interaction with a peptide, HV-3, abolishes VCP translocation to the mitochondria, corrects excessive mitophagy and reduces cell death in HD mouse- and patient-derived cells and HD transgenic mouse brains. Treatment with HV-3 reduces behavioural and neuropathological phenotypes of HD in both fragment- and full-length mtHtt transgenic mice. Our findings demonstrate a causal role of mtHtt-induced VCP mitochondrial accumulation in HD pathogenesis and suggest that the peptide HV-3 might be a useful tool for developing new therapeutics to treat HD. PMID- 27561683 TI - Being overweight may raise risk of eight more cancers, review finds. PMID- 27561684 TI - Prenatal Brain-Body Allometry in Mammals. AB - Variation in relative brain size among adult mammals is produced by different patterns of brain and body growth across ontogeny. Fetal development plays a central role in generating this diversity, and aspects of prenatal physiology such as maternal relative metabolic rate, altriciality, and placental morphology have been proposed to explain allometric differences in neonates and adults. Primates are also uniquely encephalized across fetal development, but it remains unclear when this pattern emerges during development and whether it is common to all primate radiations. To reexamine these questions across a wider range of mammalian radiations, data on the primarily fetal rapid growth phase (RGP) of ontogenetic brain-body allometry was compiled for diverse primate (np = 12) and nonprimate (nnp = 16) mammalian species, and was complemented by later ontogenetic data in 16 additional species (np = 9; nnp = 7) as well as neonatal proportions in a much larger sample (np = 38; nnp = 83). Relative BMR, litter size, altriciality, and placental morphology fail to predict RGP slopes as would be expected if physiological and life history variables constrained fetal brain growth, but are associated with differences in birth timing along allometric trajectories. Prenatal encephalization is shared by all primate radiations, is unique to the primate Order, and is characterized by: (1) a robust change in early embryonic brain/body proportions, and (2) higher average RGP allometric slopes due to slower fetal body growth. While high slopes are observed in several nonprimate species, primates alone exhibit an intercept shift at 1 g body size. This suggests that primate prenatal encephalization is a consequence of early changes to embryonic neural and somatic tissue growth in primates that remain poorly understood. PMID- 27561682 TI - Neonatal treatment with scopolamine butylbromide prevents metabolic dysfunction in male rats. AB - We tested whether treatment with a cholinergic antagonist could reduce insulin levels in early postnatal life and attenuate metabolic dysfunctions induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SLs, 3 pups/dam) and normal litters (NLs, 9 pups/dam) were used in models of early overfeeding and normal feeding, respectively. During the first 12 days of lactation, animals in the SL and NL groups received scopolamine butylbromide (B), while the controls received saline (S) injections. The drug treatment decreased insulin levels in pups from both groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, vagus nerve activity, fat tissue accretion, insulinemia, leptinemia, body weight gain and food intake. Low glucose and cholinergic insulinotropic effects were observed in pancreatic islets from both groups. Low protein expression was observed for the muscarinic M3 acetylcholine receptor subtype (M3mAChR), although M2mAChR subtype expression was increased in SL-B islets. In addition, beta-cell density was reduced in drug treated rats. These results indicate that early postnatal scopolamine butylbromide treatment inhibits early overfeeding-induced metabolic dysfunctions in adult rats, which might be caused by insulin decreases during lactation, associated with reduced parasympathetic activity and expression of M3mAChR in pancreatic islets. PMID- 27561685 TI - Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation. AB - DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short-term calorie restriction (CR) on the methylome of aged rat kidney. Whole-genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats was analyzed by methylated DNA immunoprecipitation and next-generation sequencing (MeDIP-Seq). CpG islands and repetitive regions were hypomethylated, but 5'-UTR, exon, and 3' UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short-term CR could partially ameliorate age-related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease related genes during aging may indicate increases in susceptibility to age related diseases. Therefore, the CR-induced epigenetic changes that ameliorate age-dependent aberrant methylation may be important to CR's health- and life prolonging effects. PMID- 27561687 TI - Dual-Band Dual-Mode Substrate Integrated Waveguide Filters with Independently Reconfigurable TE101 Resonant Mode. AB - A novel perturbation approach using additional metalized via-holes for implementation of the dual-band or wide-band dual-mode substrate integrated waveguide (SIW) filters is proposed in this paper. The independent perturbation on the first resonant mode TE101 can be constructed by applying the proposed perturbation approach, whereas the second resonant mode TE102 is not affected. Thus, new kinds of dual-band or wide-band dual-mode SIW filters with a fixed or an independently reconfigurable low-frequency band have been directly achieved. In order to experimentally verify the proposed design method, four two-cavity dual-band SIW filters, which have different numbers of perturbation via-holes in each cavity, and a two-cavity dual-band SIW filter, which includes four via-holes and eight reconfigurable states in each cavity, are designed and experimentally assessed. The measured results indicate that the available frequency-ratio range from 1 to 1.3 can be realized by using four two-cavity dual-band SIW filters. The center frequency of the first band can be tuned from 4.61 GHz to 5.24 GHz, whereas the center frequency of the second one is fixed at around 6.18 GHz for the two-cavity dual-band SIW filter with four reconfigurable states via-holes. All the simulated and measured results show an acceptable agreement with the predicted data. PMID- 27561686 TI - Cinnamaldehyde, Carvacrol and Organic Acids Affect Gene Expression of Selected Oxidative Stress and Inflammation Markers in IPEC-J2 Cells Exposed to Salmonella typhimurium. AB - Essential oils and organic acids are used as feed additives to improve health status and reduce colonization with pathogens. Although bactericidal in vitro, concentrations achieved in the animal gut are probably not lethal to pathogens. The aim of this study was to investigate the effects of cinnamaldehyde, carvacrol and cinnamic, lactic and propionic acids on the ability of Salmonella typhimurium ATCC 14028 (ST) to invade intestinal epithelial cells (IPEC-J2) and on the expression levels of immune related genes in the cells. The minimum inhibitory concentration (MIC) and non-inhibitory concentration (NIC) were determined and influence on the invasion capacity of ST was investigated. The structure of fimbriae and flagella was analysed by electron microscopy, and expression levels of HSP70, IkBa, IL-8 and IL-10 in the IPEC-J2 cells were carried out by q-PCR. Cinnamaldehyde, carvacrol and cinnamic and propionic acids inhibited ST invasion but not cell viability, bacterial viability and motility or the development of flagella. Propionic acid and cinnamaldehyde in combination with cinnamic acid caused structural impairment of fimbriae. Cinnamaldehyde up-regulated expression of HSP70 irrespective of the presence of organic acids or ST; exposure to carvacrol induced HSP70 only in the presence of propionic acid and ST. (c) 2016 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd. PMID- 27561688 TI - Erratum to: Comparative transcriptomics reveals the conserved building blocks involved in parallel evolution of diverse phenotypic traits in ants. PMID- 27561690 TI - Immune-mediated nephropathies in kidney transplants: recurrent or de novo diseases. AB - IMN contribute to ESRD in 13% children with renal transplant (txp). Recurrent or de novo IMN can cause graft dysfunction and/or failure, but the details regarding incidence, therapy, and outcome remain poorly understood. Retrospective single center study of all pediatric kidney txp was carried out since 1998. Clinical presentation, pathology, therapy, and graft outcomes of children with recurrent or de novo IMN were reviewed. IMN was the primary etiology of ESRD in 28 of the 149 txp recipients. Eleven children had biopsy-proven post-txp IMN-six were recurrent and five had de novo. Presentation varied with changes in SCr and/or proteinuria. Initial therapy included higher doses of steroids, MMF, and tacrolimus. Outcome was excellent with only one late graft loss. Full remission was achieved in all other patients, but some had re-recurrence of the IMN. Median follow-up time was 11.8 years. IMN (recurrent or de novo) occurred in 7.4% (11 of 149) of all kidney txp performed at our center. IMN post-txp was often seen late post-txp, usually asymptomatic and noted to have relapsing pattern. Early diagnosis and prompt therapy resulted in excellent long-term outcome in children diagnosed with post-txp IMN. PMID- 27561689 TI - Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-lambda2 or IL-29/IFN-lambda1. AB - Interleukin (IL)-28A/interferon (IFN)-lambda2 and IL-29/IFN-lambda1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, we constructed an adenovirus vector expressing either IL-28A/IFN-lambda2 (AdIL-28A) or IL-29/IFN-lambda1 (AdIL-29) to evaluate the therapeutic properties of intratumoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections of either AdIL-28A or AdIL-29 when compared with AdNull. In vivo cell depletion experiments displayed that both NK cells and CD8(+) T cells have a major role in AdIL-28A-mediated tumor growth suppression. A significant increase in the number of infiltrating CD8(+) T cells into the tumors treated with either AdIL-28A or AdIL-29 was observed. Moreover, specific anti-tumor cytotoxic T lymphocyte reactivity was detected in spleen cells from animals treated with either AdIL-28A or AdIL-29. In IFN-gamma deficient mice, anti-tumor activities of AdIL-28A were completely impaired, indicating that IFN-gamma is critically involved in the tumor growth inhibition triggered by AdIL-28A. IL-12 provided a synergistic anti-tumor effect when combined with AdIL-28A. These results indicate that AdIL-28A and AdIL-29 could be successfully utilized as an alternative cancer immunogene therapy. PMID- 27561691 TI - Emotional Processing Theory Put to Test: A Meta-Analysis on the Association Between Process and Outcome Measures in Exposure Therapy. AB - : In order to test the predictions derived from emotional processing theory (EPT), this meta-analysis examined correlations between outcome of exposure therapy and three process variables: initial fear activation (IFA), within session habituation (WSH) and between-session habituation (BSH). Literature search comprised a keyword-based search in databases, a reverse search and the examination of reference lists. Of the 21 studies included in the analyses, 17 provided data concerning IFA (57 endpoints, total N = 490), five concerning WSH (7 endpoints, total N = 116) and eight concerning BSH (22 endpoints, total N = 304). Owing to this data structure, analyses were performed using robust variance estimation with random-effects models being assumed a priori. Results indicated that WSH and BSH are positively related to treatment outcome. By contrast, the statistical association between IFA and outcome of exposure was not confirmed, whereas our moderator analysis suggested that physiological process measures lead to higher correlations than non-physiological ones. The results for IFA and BSH were affected by selective reporting. In sum, our results do not specifically strengthen EPT while matching other theoretical perspectives such as inhibitory learning and reality testing. Further research is needed to provide recommendations concerning the best way of delivering exposure therapy. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: This meta-analysis examined three variables of emotional processing theory (EPT). Initial fear activation was not linearly related to outcomes of exposure therapy. Habituation within and between sessions were shown to correlate with outcome. Outcome reporting bias was shown to play a crucial role in this meta-analysis. Results do not specifically support EPT. PMID- 27561693 TI - Prediction of stillbirth from maternal demographic and pregnancy characteristics. AB - OBJECTIVES: To develop a model for prediction of stillbirth based on maternal characteristics and components of medical history and to evaluate the performance of screening with this model for all stillbirths and those due to impaired placentation and to unexplained causes. METHODS: This was a prospective screening study of 113 415 singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation and at 19 + 0 to 24 + 6 weeks. The study population included 113 019 live births and 396 (0.35%) antepartum stillbirths; 230 (58%) were secondary to impaired placentation and 166 (42%) were due to other or unexplained causes. Multivariable logistic regression analysis was used to determine the factors from maternal characteristics and medical history which provided a significant contribution to the prediction of stillbirth. RESULTS: The risk for stillbirth increased with maternal weight (odds ratio (OR), 1.01 per kg above 69 kg), was higher in women of Afro-Caribbean racial origin (OR, 2.01), those with assisted conception (OR, 1.79), cigarette smokers (OR, 1.71), and in those with a history of chronic hypertension (OR, 2.62), systemic lupus erythematosus/antiphospholipid syndrome (OR, 3.61) or diabetes mellitus (OR, 2.55) and was increased in women with a history of previous stillbirth (OR, 4.81). Screening with the model predicted 26% of unexplained stillbirths and 31% of those due to impaired placentation, at a false-positive rate of 10%; within the impaired-placentation group the detection rate of stillbirth < 32 weeks' gestation was higher than that of stillbirth >= 37 weeks (38% vs 28%). CONCLUSIONS: A model based on maternal characteristics and medical history recorded in early pregnancy can potentially predict one-third of subsequent stillbirths. The extent to which such stillbirths could be prevented remains to be determined. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27561692 TI - ALK gene copy number gains in non-small-cell lung cancer: prognostic impact and clinico-pathological correlations. AB - BACKGROUND: The correlation between ALK gene copy number gain (ALK-CNG) and prognosis in the context of advanced non-small-cell lung cancer (NSCLC) remains a controversial issue. This study aimed to evaluate the association among ALK-CNG according to Fluorescent In Situ Hybridization (FISH), clinical characteristics and survival in resectable and advanced NSCLC. METHODS: Clinical and pathological data of patients with resectable and advanced NSCLC were retrospectively collected. Tumor tissues were analyzed for ALK-CNG by FISH, and patients were divided in 3 groups/patterns on the basis of ALK signals: disomic [Pattern A], 3 7 signals [Pattern B], >7 signals [Pattern C]. The association between clinical and pathological features and ALK-CNG patterns was evaluated. Disease/progression free and overall survival (DFS/PFS and OS) were estimated using the Kaplan-Meyer method. RESULTS: A number of 128 (76.6 %) out of the 167 eligible patients were evaluable for ALK-CNG, displaying pattern A, B and C in 71 (42.5 %), 42 (25.1 %) and 15 (9 %) patients, respectively. Gains in ALK-CNG appear to be more frequent in smokers/former smokers than in non-smokers (74.2 % versus 20.4 %, respectively, p = 0.03). Pattern A and C seem more frequently associated with higher T-stage (T3-4), while pattern B appears more represented in lower T-stage (T 1-2) (p = 0.06). No significant differences in survival rate were observed among the above groups. CONCLUSIONS: A high ALK-CNG pattern might be associated with smoking status and theoretically it might mirror genomic instability. The implications for prognosis should be prospectively investigated and validated in larger patients' series. TRIAL REGISTRATION: We confirm that all the study was performed in accordance with relevant guidelines and regulations and that all the protocol (part of a larger project MFAG 2013 N.14282) was approved by the local Ethics Committee of the Azienda Ospedaliera Universitaria Integrata of Verona on November 11st, 2014. PMID- 27561695 TI - Risk Factors for Readmission in Patients With Cancer Comanaged by Hospitalists. AB - Little is known about which variables put patients with cancer at risk for 30-day hospital readmission. Comanagement of this often complex patient population by specialists and hospitalists has become increasingly common. This retrospective study examined inpatients with cancer comanaged by hospitalists, hematologists, and oncologists to determine the rate of readmission and factors associated with readmission. Patients in this cohort had a readmission rate of 23%. Patients who were discharged to a skilled nursing facility (odds ratio [OR] = 0.34) or hospice (OR = 0.11) were less likely to have 30-day readmissions, whereas patients who had surgery (OR = 3.16) during their index admission were more likely. Other factors, including patient demographics, cancer types, and hospitalization interventions and events, did not differ between patients who were readmitted and those who were not. These findings contribute to a growing body of literature identifying risk factors for readmission in medical oncology and hematology patients. PMID- 27561694 TI - Stress, sex, and the enteric nervous system. AB - Made up of millions of enteric neurons and glial cells, the enteric nervous system (ENS) is in a key position to modulate the secretomotor function and visceral pain of the gastrointestinal tract. The early life developmental period, through which most of the ENS development occurs, is highly susceptible to microenvironmental perturbation. Over the past decade, accumulating evidence has shown the impact of stress and early life adversity (ELA) on host gastrointestinal pathophysiology. While most of the focus has been on alterations in brain structure and function, limited experimental work in rodents suggest that the enteric nervous system can also be directly affected, as shown by changes in the number, phenotype, and reactivity of enteric nerves. The work of Medland et al. in the current issue of this journal demonstrates that such alterations also occur in pigs, a larger mammalian species with high translational value to human. This work also highlights a sex-differential susceptibility of the ENS to the effect of ELA, which could contribute to the higher prevalence of GI disorders in women. In this mini-review, we will discuss the development and composition of the ENS and related gastrointestinal sensory motor and secretory functions. We will then focus on the influence of stress on the enteric nervous system, with a particular emphasis on neurodevelopmental changes. Finally, we will discuss the influence of sex on those parameters. PMID- 27561697 TI - Successful Treatment of Epstein-Barr Virus-Associated Lymphoproliferative Disorder with Rituximab in a Patient Undergoing Immunosuppressive Therapy for Aplastic Anemia. AB - Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is a currently emerging serious complication in immunosuppressed patients, especially in allogeneic transplant recipients. Several fatal cases of EBV-LPD have been reported in aplastic anemia (AA) patients receiving immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine A (CsA), but no appropriate prophylactic or therapeutic strategy has been established. Herein, we describe a 29-year-old man whose EBV-LPD was successfully treated with rituximab. He received IST with ATG plus CsA for hepatitis-associated AA. EBV-DNA in plasma, which was not detectable before IST, gradually increased after IST initiation. A high fever and systemic lymphadenopathy developed 31 days after IST initiation. An EBV-DNA titer of 5.7 * 105 copies/MUl was detected, and a diagnosis of EBV-LPD was made. Although discontinuation of IST was not effective, a single dose of rituximab on day 33 resolved the clinical symptoms and completely eliminated EBV DNA. Even after restarting CsA administration, no elevation of EBV-DNA was observed, and his complete blood cell count had fully recovered 1 year after IST. This case suggests that this treatment strategy for EBV-LPD with EBV-DNA monitoring and rituximab administration, which has been recommended in allogeneic transplant recipients, may also be useful in the context of AA patients receiving IST. PMID- 27561696 TI - Identification and Characterization of Adverse Drug Events in Primary Care. AB - The purpose of this study was to identify and characterize adverse drug events (ADEs) in a primary care setting using an electronic health record (EHR). This prospective, observational study enrolled patients with any medication change who were seen at an outpatient internal medicine clinic. Patients were evaluated for ADEs by EHR review and telephone interview. ADEs were independently assessed for causality, severity, preventability, and ameliorability by a physician and a pharmacist using a grading instrument. There were 1368 unique medication changes for 701 individuals who completed the study (1.95 changes per person). Of the 226 suspected ADEs, 68 (58%) were deemed to be "definite" or "probable" following causality assessment; 21% were preventable and 40% ameliorable. Only 2 ADEs were serious or life-threatening. Compared with prior reports, ADEs in primary care have decreased in frequency and severity, yet the occurrence of preventable and ameliorable ADEs has increased. PMID- 27561698 TI - Effect of the Hemochromatosis Mutations on Iron Overload among the Indian beta Thalassemia Carriers. AB - BACKGROUND: Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron absorption.HFE gene mutations C282Y and H63D are responsible for the majority of hereditary hemochromatosis cases. METHODS: We tried to look at the effect of HFE mutations on the iron status. A total of 100 beta thalassemia traits (BTT) with 100 normal individuals were screened for the C282Y and H63D mutations using PCR-RFLP. The serum ferritin levels were determined using ELISA kit. RESULTS: We did not find the C282Y mutation in our study group. The allelic frequencies for H63D mutation did not differ significantly between beta-thalassemia traits (8.5%) and normal controls (9%). BetaTauTau with H63D genotype of H/D (143.16 +/- 80.3 ng/ml) and D/D (504 ng/ml) showed higher ferritin levels as against H/H genotype (88.64 +/- 92.43 ng/ml). The statistically significant difference was observed in the mean serum ferritin levels among the individuals showing H/H and D/D genotypes (P < 0.002) and H/D and D/D genotype (P < 0.01) in both the groups. CONCLUSION: This suggests that iron load in BTT tends to aggravated with the co-inheritance of the H63D mutation. The mutant H63D gene showed the presence of haplotype 6 which is reported in the European population suggesting a common origin. PMID- 27561700 TI - "If it looks like a duck..." - why humans need to focus on different approaches than insects if we are to become efficiently and effectively ultrasocial. AB - The parallels between the agricultural successes of ultrasocial insects and those of humans are interesting and potentially important. There are a number of important caveats, however, including the relative complexities of insect reproduction, their more rigidly determined altricial patterns of social behaviour, the roles of post-reproductive group members, and differences in the known factors involved in ultrasocietal collapse. PMID- 27561699 TI - Impact of changing indications and increased utilization of fetal echocardiography on prenatal detection of congenital heart disease. AB - BACKGROUND: Antenatal diagnosis of congenital heart defects (CHD) can impact outcomes in neonates with severe CHD. Obstetric screening guidelines and the indications for fetal echocardiography (FE) have evolved in an attempt to improve the early prenatal detection of CHD. Analyzing yield for specific indications will help clinicians better stratify at-risk pregnancies. METHODS: Retrospective cohort study of all FE performed between 2000 and 2010 at a single tertiary care academic medical center in New York City. A total of 9878 FE met inclusion criteria for our study. In cases of multiple gestations (MG), each fetus was counted as a separate study. RESULTS: The number of new diagnosis of fetal CHD by FEs increased 200%. There was a statistically significant increase in those referred for suspected CHD, increased nuchal translucency (NT), MG, and suboptimal imaging (P < .001). The indication of "suboptimal imaging" (SO) not only accounted for 5.23% of all referrals from 2000 to 2002, compared to 22.26% of all referrals from 2008 to 2010 (P < .0001), but also had the lowest yield for diagnoses of CHD (P < .02). CONCLUSIONS: Over the past decade, there has been an increase in utilization of FE with a proportional increase in prenatally diagnosed CHD. For indications such as suspected CHD, NT and MG increases in referrals have led to a proportionate increase in fetal diagnosis of CHD. SO as an indication has the lowest yield of fetal diagnosis of CHD. Antenatal detection of CHD may be improved by a change in obstetric imaging protocols to ensure appropriate referrals. PMID- 27561701 TI - Analyzing video recorded support of postnatal transition in preterm infants following a c-section. AB - BACKGROUND: Over the past years, research on neonatal resuscitation has focused on single interventions. The present study was performed to analyze the process quality of delivery room management of preterm infants born by c-section in our institution. METHODS: We performed a cross-sectional study of videos of preterm infants born by c-section. Videos were analyzed according to time point, duration and number of performed medical interventions. The study period occurred between January 2012 and December 2013. Infants were caterogized in 3 groups according to their gestational age. RESULTS: One hundred eleven videos were analyzed. 100 (90 %) of the infants were transferred to NICU and 91 (83 %) received respiratory support after a median of 0.5 min. All infants were auscultated after 8 (5-16) seconds median (IQR) and an oxygen saturation sensor was placed after 37 (28-52) seconds. 23 infants were intubated after 9 (6-17) minutes and 17 received exogenous surfactant; 29 % according to INSURE (intubation-surfactant-extubation) technique. The duration of intubation attempts was 47 (25-60) seconds. 51 % of the newborns received a sustained inflation for 8 (6-9) seconds. A successful IV line placement occurred after 15 (12-20) minutes. 4 % of the infants were transported to the NICU without an IV-line after 3 (difference range: 2-5) unsuccessful attempts. CONCLUSIONS: Using video analysis as a tool to study process quality, we conclude that interventions differ not only between but also within similar age groups. This data can be used for benchmarking with current guidelines and practice in other centers. PMID- 27561702 TI - Estimation of excitatory and inhibitory synaptic conductance variations in motoneurons during locomotor-like rhythmic activity. AB - The rhythmic activity of motoneurons (MNs) that underlies locomotion in mammals is generated by synaptic inputs from the locomotor network in the spinal cord. Thus, the quantitative estimation of excitatory and inhibitory synaptic conductances is essential to understand the mechanism by which the network generates the functional motor output. Conductance estimation is obtained from the voltage-current relationship measured by voltage-clamp- or current-clamp recording with knowledge of the leak parameters of the recorded neuron. However, it is often difficult to obtain sufficient data to estimate synaptic conductances due to technical difficulties in electrophysiological experiments using in vivo or in vitro preparations. To address this problem, we estimated the average variations in excitatory and inhibitory synaptic conductance during a locomotion cycle from a single voltage trace without measuring the leak parameters. We found that the conductance variations can be accurately reconstructed from a voltage trace of 10 cycles by analyzing synthetic data generated from a computational model. Next, the conductance variations were estimated from mouse spinal MNs in vitro during drug-induced-locomotor-like activity. We found that the peak of excitatory conductance occurred during the depolarizing phase of the locomotor cycle, whereas the peak of inhibitory conductance occurred during the hyperpolarizing phase. These results suggest that the locomotor-like activity is generated by push-pull modulation via excitatory and inhibitory synaptic inputs. PMID- 27561703 TI - Cardiotoxicity of Aromatase Inhibitors in Breast Cancer Patients. AB - Aromatase inhibitors represent an effective endocrine treatment for patients with hormone receptor-positive breast cancer, in early stage and in metastatic disease. However, by decreasing levels of serum estrogens they also potentially reduce the protective effect of estrogens on the cardiovascular system. Patients treated with aromatase inhibitors, in fact, compared with those who receive tamoxifen, more often develop hyperlipidemia, hypercholesterolemia, and hypertension, which are recognized risk factors for cardiovascular disease. This might raise some concerns especially in the adjuvant setting where the aim of treatment is the cure, and for postmenopausal patients who are already at risk for cardiovascular disease. However, whether the relative higher incidence of cardiac adverse events reported with aromatase inhibitors compared with tamoxifen is related to an actual cardiac toxicity of aromatase inhibitors rather than a cardioprotective effect of tamoxifen is still unclear. In this article we review the available literature on cardiotoxicity of aromatase inhibitors and provide some practical advice to improve the cardiovascular safety profile of these drugs. PMID- 27561704 TI - Mechanisms that Increase Stability of Estrogen Receptor Alpha in Breast Cancer. AB - Estrogen receptor alpha (ER) is a transcriptional regulator that controls the expression of genes related to cellular proliferation and differentiation in normal mammary tissue. However, the expression, abundance, and activity of this receptor are increased in 70% of breast cancers. The ER upregulation is facilitated by several molecular mechanisms, including protein stability, which represents an important strategy to maintain an active and functional repertoire of ER. Several proteins interact and protect ER from degradation by the ubiquitin proteasome system. Through diverse mechanisms, these proteins prevent polyubiquitination and degradation of ER, leading to an increase in ER protein levels; consequently, estrogen signaling and its physiologic effects are enhanced in breast cancer cells. Thus, increased protein stability seems to be one of the main reasons that ER is upregulated in breast cancer. Here, we highlight findings on the proteins and mechanisms that participate directly or indirectly in ER stability and their relevance to breast cancer. PMID- 27561706 TI - Better late than Now-or-Never: The case of interactive repair phenomena. AB - Empirical evidence from dialogue, both corpus and experimental, highlights the importance of interaction in language use - and this raises some questions for Christiansen & Chater's (C&C's) proposals. We endorse C&C's call for an integrated framework but argue that their emphasis on local, individual production and comprehension makes it difficult to accommodate the ubiquitous, interactive, and defeasible processes of clarification and repair in conversation. PMID- 27561705 TI - Fractalkine suppression during hepatic encephalopathy promotes neuroinflammation in mice. AB - BACKGROUND: Acute liver failure is associated with numerous systemic consequences including neurological dysfunction, termed hepatic encephalopathy, which contributes to mortality and is a challenge to manage in the clinic. During hepatic encephalopathy, microglia activation and neuroinflammation occur due to dysregulated cell signaling and an increase of toxic metabolites in the brain. Fractalkine is a chemokine that is expressed primarily in neurons and through signaling with its receptor CX3CR1 on microglia, leads to microglia remaining in a quiescent state. Fractalkine is often suppressed during neuropathies that are characterized by neuroinflammation. However, the expression and subsequent role of fractalkine on microglia activation and the pathogenesis of hepatic encephalopathy due to acute liver failure is unknown. METHODS: Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) or saline for controls. Subsets of these mice were implanted with osmotic minipumps that infused soluble fractalkine or saline into the lateral ventricle of the brain. Neurological decline and the latency to coma were recorded in these mice, and brain, serum, and liver samples were collected. Neurons or microglia were isolated from whole brain samples using immunoprecipitation. Liver damage was assessed using hematoxylin and eosin staining and by measuring serum liver enzyme concentrations. Fractalkine and CX3CR1 expression were assessed by real-time PCR, and proinflammatory cytokine expression was assessed using ELISA assays. RESULTS: Following AOM administration, fractalkine expression is suppressed in the cortex and in isolated neurons compared to vehicle-treated mice. CX3CR1 is suppressed in isolated microglia from AOM-treated mice. Soluble fractalkine infusion into the brain significantly reduced neurological decline in AOM-treated mice compared to saline-infused AOM-treated mice. Infusion of soluble fractalkine into AOM-treated mice reduced liver damage, lessened microglia activation, and suppressed expression of chemokine ligand 2, interleukin-6, and tumor necrosis factor alpha compared to saline-infused mice. CONCLUSIONS: These findings suggest that fractalkine-mediated signaling is suppressed in the brain following the development of hepatic encephalopathy. Supplementation of AOM-treated mice with soluble fractalkine led to improved outcomes, which identifies this pathway as a possible therapeutic target for the management of hepatic encephalopathy following acute liver injury. PMID- 27561707 TI - abYsis: Integrated Antibody Sequence and Structure-Management, Analysis, and Prediction. AB - abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways-from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre analyzed sequence data from the European Molecular Biology Laboratory European Nucleotide Archive (EMBL-ENA) and Kabat as well as structure data from the Protein Data Bank. A researcher's own sequences can also be analyzed through the web interface. A defining characteristic of abYsis is that the sequences are automatically numbered with a series of popular schemes such as Kabat and Chothia and then annotated with key information such as complementarity-determining regions and potential post-translational modifications. A unique aspect of abYsis is a set of residue frequency tables for each position in an antibody, allowing "unusual residues" (those rarely seen at a particular position) to be highlighted and decisions to be made on which mutations may be acceptable. This is especially useful when comparing antibodies from different species. abYsis is useful for any researcher specializing in antibody engineering, especially those developing antibodies as drugs. abYsis is available at www.abysis.org. PMID- 27561708 TI - Non-Coding RNA Molecules Connect Calorie Restriction and Lifespan. AB - Calorie restriction (CR) is a broadly effective environmental intervention that extends life by operating through numerous biological processes. Here, we discuss how non-coding RNA (ncRNA) molecules act as mediators and targets of lifespan extending CR. We also highlight how these RNA molecules connect CR to its effects on genome stability, cell metabolism, programmed cell death, senescence, cancer, and neurodegeneration. We anticipate that an advanced understanding of the connections between CR and non-coding RNA will provide unique insights into aging mechanisms while pointing to novel approaches aimed at modulating aging and age related diseases. PMID- 27561709 TI - Long-term safety and efficacy of bilastine following up to 12 weeks or 52 weeks of treatment in Japanese patients with allergic rhinitis: Results of an open label trial. AB - OBJECTIVE: Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR). METHODS: Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements. RESULTS: Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR. CONCLUSION: Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622). PMID- 27561710 TI - Dissecting maize diversity in lowland South America: genetic structure and geographic distribution models. AB - BACKGROUND: Maize landraces from South America have traditionally been assigned to two main categories: Andean and Tropical Lowland germplasm. However, the genetic structure and affiliations of the lowland gene pools have been difficult to assess due to limited sampling and the lack of comparative analysis. Here, we examined SSR and Adh2 sequence variation in a diverse sample of maize landraces from lowland middle South America, and performed a comprehensive integrative analysis of population structure and diversity including already published data of archaeological and extant specimens from the Americas. Geographic distribution models were used to explore the relationship between environmental factors and the observed genetic structure. RESULTS: Bayesian and multivariate analyses of population structure showed the existence of two previously overlooked lowland gene pools associated with Guarani indigenous communities of middle South America. The singularity of this germplasm was also evidenced by the frequency distribution of microsatellite repeat motifs of the Adh2 locus and the distinct spatial pattern inferred from geographic distribution models. CONCLUSION: Our results challenge the prevailing view that lowland middle South America is just a contact zone between Andean and Tropical Lowland germplasm and highlight the occurrence of a unique, locally adapted gene pool. This information is relevant for the conservation and utilization of maize genetic resources, as well as for a better understanding of environment-genotype associations. PMID- 27561711 TI - In vivo bone strain in the mandibular corpus of Sapajus during a range of oral food processing behaviors. AB - It has been hypothesized that mandibular corpus morphology of primates is related to the material properties of the foods that they chew. However, chewing foods with different material properties is accompanied by low levels of variation in mandibular strain patterns in macaques. We hypothesized that if variation in primate mandible form reflects adaptations to feeding on foods with different material and geometric properties, then this variation will be driven primarily by differences in oral food processing behavior rather than differences in chewing per se. To test this hypothesis, we recorded in vivo bone strain data from the lateral and medial surfaces of the mandibular corpus during complete feeding sequences in three adult male Sapajus as they fed on foods with a range of sizes and material properties. We assessed whether variation in mandibular corpus strain regimes is associated with variation in feeding behaviors and/or chewing on different foods, and we quantified the relative variation in mandibular corpus strain regimes associated with chewing on foods of different material properties versus a range of oral food processing behaviors (incisor, premolar, and molar biting; pulling on incisors; mastication). Feeding behavior had a significant effect on mandibular corpus strain regimes, as did chewing side and the cycle number in a feeding sequence. However, food type had weaker effects and usually only through interaction effects with chewing side and/or cycle type. Strain regimes varied most across different chew sides, then across different behaviors, and lastly between mastication cycles on different foods. Strain magnitudes associated with premolar, molar, and incisor biting were larger than those recorded during mastication. These data suggest that intra- and inter specific variation in mandible morphology is a trade-off between performance requirements of different oral food processing behaviors and of variation in chewing side, with direct effects of food type being less important. PMID- 27561712 TI - Complex patterns of spatially extended generators of epileptic activity: Comparison of source localization methods cMEM and 4-ExSo-MUSIC on high resolution EEG and MEG data. AB - Electric Source Imaging (ESI) and Magnetic Source Imaging (MSI) of EEG and MEG signals are widely used to determine the origin of interictal epileptic discharges during the pre-surgical evaluation of patients with epilepsy. Epileptic discharges are detectable on EEG/MEG scalp recordings only when associated with a spatially extended cortical generator of several square centimeters, therefore it is essential to assess the ability of source localization methods to recover such spatial extent. In this study we evaluated two source localization methods that have been developed for localizing spatially extended sources using EEG/MEG data: coherent Maximum Entropy on the Mean (cMEM) and 4th order Extended Source Multiple Signal Classification (4-ExSo-MUSIC). In order to propose a fair comparison of the performances of the two methods in MEG versus EEG, this study considered realistic simulations of simultaneous EEG/MEG acquisitions taking into account an equivalent number of channels in EEG (257 electrodes) and MEG (275 sensors), involving a biophysical computational neural mass model of neuronal discharges and realistically shaped head models. cMEM and 4-ExSo-MUSIC were evaluated for their sensitivity to localize complex patterns of epileptic discharges which includes (a) different locations and spatial extents of multiple synchronous sources, and (b) propagation patterns exhibited by epileptic discharges. Performance of the source localization methods was assessed using a detection accuracy index (Area Under receiver operating characteristic Curve, AUC) and a Spatial Dispersion (SD) metric. Finally, we also presented two examples illustrating the performance of cMEM and 4-ExSo-MUSIC on clinical data recorded using high resolution EEG and MEG. When simulating single sources at different locations, both 4-ExSo-MUSIC and cMEM exhibited excellent performance (median AUC significantly larger than 0.8 for EEG and MEG), whereas, only for EEG, 4-ExSo-MUSIC showed significantly larger AUC values than cMEM. On the other hand, cMEM showed significantly lower SD values than 4-ExSo-MUSIC for both EEG and MEG. When assessing the impact of the source spatial extent, both methods provided consistent and reliable detection accuracy for a wide range of source spatial extents (source sizes ranging from 3 to 20cm2 for MEG and 3 to 30cm2 for EEG). For both EEG and MEG, 4-ExSo-MUSIC localized single source of large signal to-noise ratio better than cMEM. In the presence of two synchronous sources, cMEM was able to distinguish well the two sources (their location and spatial extent), while 4-ExSo-MUSIC only retrieved one of them. cMEM was able to detect the spatio temporal propagation patterns of two synchronous activities while 4-ExSo-MUSIC favored the strongest source activity. Overall, in the context of localizing sources of epileptic discharges from EEG and MEG data, 4-ExSo-MUSIC and cMEM were found accurately sensitive to the location and spatial extent of the sources, with some complementarities. Therefore, they are both eligible for application on clinical data. PMID- 27561714 TI - Synthesis and antinociceptive activity of new 2-substituted 4-(trifluoromethyl) 5,6-dihydrobenzo[h]quinazolines. AB - A useful synthetic route for an initial new series of 2-substituted 4 (trifluoromethyl)-5,6-dihydrobenzo[h]quinazolines (3), as well as an evaluation of their analgesic effect in a mice pain model, is reported. Five new quinazolines were formed from the cyclocondensation reactions of 2,2,2-trifluoro 1-(1-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)ethanone (1) with some well-known amidine salts [NH2CR(=NH)] (2), in which R=H, Me, Ph, NH2 and SMe, at a 40-70% yield. Subsequently, due to the importance of the pyrrole nucleus, a 2-(pyrrol-1 yl)quinazoline (4) was obtained through a Clauson-Kaas reaction from the respective 2-(amino)quinazoline, in a reaction with 2,5-dimethoxy tetrahydrofuran. The analgesic evaluation demonstrated that four 5,6 dihydrobenzo[h]quinazolines (compounds of 3c (R=Ph), 3d (R=NH2), 3e (R=SMe), and 4 (R=pyrrol-1-yl); 100mg/kg, p.o.) and ketoprofen (100mg/kg, p.o.) significantly reduced the spontaneous nociception in a capsaicin-induced test. Moreover, in comparison with ketoprofen (100 and 300mg/kg, p.o.), compound 3c (30-300mg/kg, p.o.) showed an anti-hyperalgesic action in an arthritic pain model without locomotor alterations in the mice, suggesting that quinazoline 3c is a promising prototype scaffold for new analgesic drugs in the treatment of pathological pain such as that in arthritis. PMID- 27561713 TI - Adult age differences in subcortical myelin content are consistent with protracted myelination and unrelated to diffusion tensor imaging indices. AB - Post mortem studies suggest protracted myelination of subcortical white matter into the middle age followed by gradual decline in the late adulthood. To date, however, establishing the proposed inverted-U pattern of age-myelin association proved difficult, as the most common method of investigating white matter, diffusion tensor imaging (DTI), usually reveals only linear associations between DTI indices and age among healthy adults. Here we use a novel method of estimating Myelin Water Fraction (MWF) based on modeling the short spin-spin (T2) relaxation component from multi-echo T2 relaxation imaging data and assess subcortical myelin content within six white matter tracts in a sample of healthy adults (N=61, age 18-84 years). Myelin content evidenced a quadratic relationship with age, in accord with the pattern observed postmortem studies. In contrast, DTI-derived indices that are frequently cited as proxies for myelination, fractional anisotropy (FA) and radial diffusivity (RD), exhibited linear or null relationships with age. Furthermore, the magnitude of age differences in MWF varied across the white matter tracts. Myelin content estimated by MWF was unrelated to FA and correlated with RD only in the splenium. These findings are consistent with the notion that myelination continues throughout the young adulthood into the middle age. The results demonstrate that single-tensor DTI cannot serve as a source of specific proxies for myelination of white matter tracts. PMID- 27561715 TI - Role of a gitogenin-type steroidal saponin (3-O-beta-d-glucopyranosyl (1->2)-beta d-glucopyranosyl (1->4)-beta-d-galactopyranoside-25R,5alpha-spirostane 2alpha,3beta-diol), isolated from the leaves of Malvastrum coromandelianum in regulating thyrotoxicosis in rats. AB - The hitherto unknown role of saponin in the regulation of thyrotoxicosis has been revealed in chemically-induced thyrotoxic rats. l-T4 (l-thyroxine) administration at pre-standardized dose of 500-MUg/kg body weight for 12days increased the levels of thyroid hormones, enhanced the activity of hepatic 5'-monodeiodinase I (5'DI) and glucose-6-phosphatase (G-6Pase) as well as lipid peroxidation (LPO) with a parallel decrease in the levels of antioxidative enzymes. However, administration of the isolated saponin for 15days ameliorated the T4-induced alterations in serum thyroid hormones, hepatic LPO, G-6-Pase and 5'DI activity, and improved the cellular antioxidant status, indicating its antithyroidal and antioxidative potential. These effects of the test compound were comparable to a reference antithyroid drug, Propylthiouracil (PTU), suggesting that the test saponin may act as a potent anti-thyroid agent. PMID- 27561716 TI - Development of single and mixed isoform selectivity PI3Kdelta inhibitors by targeting Asn836 of PI3Kdelta. AB - A series of PI3Kdelta inhibitors derived from the pan-PI3K inhibitor ZSTK474 was prepared that target a non-conserved region of the catalytic site. Dependent upon the substituents present, these analogues show different levels of isoform selectivity and sensitivity to the mutation N836D in PI3Kdelta. As a marker of 'on-target' activity and permeability, a selection of the most potent PI3Kdelta inhibitors were shown to inhibit pAkt production in the Nawalma Burkitt lymphoma cell line. PMID- 27561717 TI - Synthesis and hypoglycemic activity of 9-O-(lipophilic group substituted) berberine derivatives. AB - A series of 9-O-(lipophilic group substituted) berberine derivatives were synthesized and evaluated for their cytotoxicity and hypoglycemic activity against HepG2 cells. All the results indicated that most of the synthesized compounds exhibited lower cytotoxicity and a certain degree of hypoglycemic activity. Especially the compounds 5g and 5h displayed dramatically increased hypoglycemic activity compared with berberine, and the cytotoxicity maintained or even lower than berberine, indicating that they are potential candidates for new anti-type 2 diabetes mellitus drugs. PMID- 27561718 TI - Synthesis of novel 25-hydroxyprotopanaxadiol derivatives by methylation and methoxycarbonylation using dimethyl carbonate as a environment-friendly reagent and their anti-tumor evaluation. AB - A previous study involving 25-hydroxyprotopanaxadiol (25-OH-PPD) illustrated that the anti-cancer activity increased by 1-3 times after C-3/C-12-OH was substituted by short-chain fatty acids. In addition, 25-OCH3-PPD was also one of our research interests; the unique difference in structure between 25-OH-PPD and 25-OCH3-PPD is that in C-25, the latter activity was 2-5 times higher than that of 25-OH-PPD. These data serves as the scientific basis of our continuing research. To further confirm the effect of short chain acylated and methylated products on the activity and to identify more potent, higher selectivity compounds, we modified 25-OH-PPD with a green environment-friendly and non-toxic chemical dimethyl carbonate (DMC), which plays the role of both solvent and reagent. This experiment yielded 14 derivatives. Their in vitro anti-tumor activities were tested on two different human tumor cell lines (HeLa and DU145) and one normal cell line (IOSE144) by standard MTT assay. The results showed that compounds 3, 5, 6, 10, 11, 12, and 13 exhibited higher cytotoxic activity on two cell lines, with IC50 values within the range of 1.1-12MUM. Compounds 12 and 13 exhibited the highest potent activity, with IC50 values of 1.1 and 1.2MUM, respectively, on HeLa cells. Antitumor activity significantly increased after the hydroxyl groups are substituted by methyl. The results of the present study may provide useful data for evaluating the structure-activity relationships of other dammarane-type sapogenins and developing new antitumor agents. PMID- 27561719 TI - Synthesis of novel nicotinohydrazide and (1,3,4-oxadiazol-2-yl)-6 (trifluoromethyl)pyridine derivatives as potential anticancer agents. AB - A series of novel nicotinohydrazide derivatives 6a-g and 1,3,4-oxadiazole functionalized pyridine derivatives 7a-k and 8a-d were prepared in series of steps. All the compounds were screened for cytotoxicity against HeLa (cervical), DU145 (prostate), HepG2 (liver) and MBA-MB-231 (breast) human cancer cell lines. Compounds 6h, 6i, 7d, 7h, 7i and 8b which showed promising cytotoxicity at <15MUM concentration have been identified. Further optimization of the structure is underway to identify a lead compound. PMID- 27561721 TI - The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent. AB - Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were 'donor found' and 'transplantation reached'. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non Northwestern European patients (P<0.0001). Non-Northwestern European patients more often needed a cord blood transplant. The degree of HLA matching was significantly lower for non-Northwestern European patients (P<0.0006). The time needed to identify a donor decreased for both populations. The percentage of Northwestern European patients reaching transplantation increased from 77% to 83% and for non-Northwestern European patients from 57% to 72% (P=0.0003). The increase of the global inventory resulted in more transplants for patients lacking a family donor, although the quality and quantity of (potential) haematopoietic cell grafts for patients of a non-Northwestern European descent remained inferior, indicating the need for adaptation of recruitment. PMID- 27561720 TI - Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia. AB - The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26 64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. PMID- 27561723 TI - Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms. AB - BACKGROUND: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PURPOSE: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. METHODS: 192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. RESULTS: Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) - 1.96; 95% CI - 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR - 2.17; 95% CI - 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR - 0.55, 95% CI - 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR - 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR - 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism' analyzed. CONCLUSION: These results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma. PMID- 27561722 TI - Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis. AB - Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was a genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult patients (median age: 42 years) with B-cell precursor ALL (BCP-ALL) were classified as having Ph-like ALL using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and KMT2A-rearrangements. IGH-CRLF2 rearrangements (6/16; P=0.002) and mutations in JAK2 (7/16; P<0.001) were found exclusively in the Ph-like ALL subgroup. Clinical and outcome analyses were restricted to patients treated in German Multicenter Study Group for Adult ALL (GMALL) trials 06/99 and 07/03 (n=107). The complete remission rate was 100% among both Ph-like ALL patients (n=19) and the "remaining BCP-ALL" cases (n=40), i.e. patients negative for BCR-ABL1 and KMT2A-rearrangements and the Ph-like subtype. Significantly fewer Ph-like ALL patients reached molecular complete remission (33% versus 79%; P=0.02) and had a lower probability of continuous complete remission (26% versus 60%; P=0.03) and overall survival (22% versus 64%; P=0.006) at 5 years compared to the remaining BCP-ALL patients. The profile of genetic lesions in adults with Ph-like ALL, including older adults, resembles that of pediatric Ph-like ALL and differs from the profile in the remaining BCP ALL. Our study is the first to demonstrate that Ph-like ALL is associated with inferior outcomes in intensively treated older adult patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed. (NCT00199056, NCT00198991). PMID- 27561724 TI - Genome-wide characterization of microsatellites in Triticeae species: abundance, distribution and evolution. AB - Microsatellites are an important constituent of plant genome and distributed across entire genome. In this study, genome-wide analysis of microsatellites in 8 Triticeae species and 9 model plants revealed that microsatellite characteristics were similar among the Triticeae species. Furthermore, genome-wide microsatellite markers were designed in wheat and then used to analyze the evolutionary relationship of wheat and other Triticeae species. Results displayed that Aegilops tauschii was found to be the closest species to Triticum aestivum, followed by Triticum urartu, Triticum turgidum and Aegilops speltoides, while Triticum monococcum, Aegilops sharonensis and Hordeum vulgare showed a relatively lower PCR amplification effectivity. Additionally, a significantly higher PCR amplification effectivity was found in chromosomes at the same subgenome than its homoeologous when these markers were subjected to search against different chromosomes in wheat. After a rigorous screening process, a total of 20,666 markers showed high amplification and polymorphic potential in wheat and its relatives, which were integrated with the public available wheat markers and then anchored to the genome of wheat (CS). This study not only provided the useful resource for SSR markers development in Triticeae species, but also shed light on the evolution of polyploid wheat from the perspective of microsatellites. PMID- 27561726 TI - Assessment of Metformin-Induced Changes in Cardiac and Hepatic Redox State Using Hyperpolarized[1-13C]Pyruvate. AB - Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment on heart and liver pyruvate metabolism in rats in vivo. Both oral treatment for 4 weeks and a single intravenous metformin infusion significantly increased the cardiac [1-13C]lactate:[1-13C]pyruvate ratio but had no effect on the [1 13C]bicarbonate + 13CO2:[1-13C]pyruvate ratio, an index of pyruvate dehydrogenase flux. These changes were paralleled by a significant increase in the heart and liver cytosolic redox state, estimated from the [lactate]:[pyruvate] ratio but not the whole-cell [NAD+]/[NADH] ratio. Hyperpolarized MRI localized the increase in cardiac lactate to the left ventricular myocardium, implying a direct myocardial effect, though metformin had no effect on systolic or diastolic cardiac function. These findings demonstrate the ability of hyperpolarized pyruvate magnetic resonance spectroscopy to detect metformin-induced changes in cytosolic redox biology, suggest that metformin has a previously unrecognized effect on cardiac redox state, and help to refine the design of impending hyperpolarized magnetic resonance studies in humans. PMID- 27561727 TI - Adipose Recruitment and Activation of Plasmacytoid Dendritic Cells Fuel Metaflammation. AB - In obese individuals, visceral adipose tissue (VAT) is the seat of chronic low grade inflammation (metaflammation), but the mechanistic link between increased adiposity and metaflammation largely remains unclear. In obese individuals, deregulation of a specific adipokine, chemerin, contributes to innate initiation of metaflammation by recruiting circulating plasmacytoid dendritic cells (pDCs) into VAT through chemokine-like receptor 1 (CMKLR1). Adipose tissue-derived high mobility group B1 (HMGB1) protein activates Toll-like receptor 9 (TLR9) in the adipose-recruited pDCs by transporting extracellular DNA through receptor for advanced glycation end products (RAGE) and induces production of type I interferons (IFNs). Type I IFNs in turn help in proinflammatory polarization of adipose-resident macrophages. IFN signature gene expression in VAT correlates with both adipose tissue and systemic insulin resistance (IR) in obese individuals, which is represented by ADIPO-IR and HOMA2-IR, respectively, and defines two subgroups with different susceptibility to IR. Thus, this study reveals a pathway that drives adipose tissue inflammation and consequent IR in obesity. PMID- 27561725 TI - Insulin Downregulates the Transcriptional Coregulator CITED2, an Inhibitor of Proangiogenic Function in Endothelial Cells. AB - In patients with atherosclerotic complications of diabetes, impaired neovascularization of ischemic tissue in the myocardium and lower limb limits the ability of these tissues to compensate for poor perfusion. We identified 10 novel insulin-regulated genes, among them Adm, Cited2, and Ctgf, which were downregulated in endothelial cells by insulin through FoxO1. CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), which was downregulated by insulin by up to 54%, is an important negative regulator of hypoxia-inducible factor (HIF) and impaired HIF signaling is a key mechanism underlying the impairment of angiogenesis in diabetes. Consistent with impairment of vascular insulin action, CITED2 was increased in cardiac endothelial cells from mice with diet-induced obesity and from db/db mice and was 3.8-fold higher in arterial tissue from patients with type 2 diabetes than control subjects without diabetes. CITED2 knockdown promoted endothelial tube formation and endothelial cell proliferation, whereas CITED2 overexpression impaired HIF activity in vitro. After femoral artery ligation, induction of an endothelial-specific HIF target gene in hind limb muscle was markedly upregulated in mice with endothelial cell deletion of CITED2, suggesting that CITED2 can limit HIF activity in vivo. We conclude that vascular insulin resistance in type 2 diabetes contributes to the upregulation of CITED2, which impairs HIF signaling and endothelial proangiogenic function. PMID- 27561729 TI - Music Therapy for Preterm Infants and Their Parents: A Meta-analysis. AB - CONTEXT: Given the recent expansion of research in the area of music therapy (MT) for preterm infants, there is a need for an up-to-date meta-analysis of rigorously designed studies that focus exclusively on MT. OBJECTIVE: To systematically review and meta-analyze the effect of MT on preterm infants and their parents during NICU hospitalization and after discharge from the hospital. DATA SOURCES: PubMed/Medline, PsycINFO, Embase, Cochrane Database of Systematic Reviews, CINAHL, ERIC, Web of Science, RILM. STUDY SELECTION: Only parallel or crossover randomized controlled trials of MT versus standard care, comparison therapy, or placebo were included. DATA EXTRACTION: Independent extraction by 2 reviewers, including risk of bias indicators. RESULTS: From 1803 relevant records, 16 met inclusion criteria, of which 14 contained appropriate data for meta-analysis involving 964 infant participants and 266 parent participants. Overall, random-effects meta-analyses suggested significant large effects favoring MT for infant respiratory rate (mean difference, -3.91/min, 95% confidence interval, -7.8 to -0.03) and maternal anxiety (standardized mean difference, -1.82, 95% confidence interval, -2.42 to -1.22). There was not enough evidence to confirm or refute any effects of MT on other physiologic and behavioral outcomes or on short-term infant and service-level outcomes. There was considerable heterogeneity between studies for the majority of outcomes. LIMITATIONS: This review is limited by a lack of studies assessing long-term outcomes. CONCLUSIONS: There is sufficient evidence to confirm a large, favorable effect of MT on infant respiratory rate and maternal anxiety. More rigorous research on short-term and long-term infant and parent outcomes is required. PMID- 27561728 TI - Prognostic Disclosures to Children: A Historical Perspective. AB - Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Before 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a "protective" approach to disclosure, where children were shielded from the harms of bad news. We identified 4 main arguments in the literature at this time supporting this "protective" approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more "open" approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this "open" approach. Then, by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from "never tell" to "always tell." In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple "black-and-white" recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight 4 categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. PMID- 27561730 TI - Initial Experience With Propranolol Treatment of Lymphatic Anomalies: A Case Series. AB - Lymphatic malformations (LMs) are congenital lymphatic lesions that impose significant and costly morbidities on affected patients. Treatment options are limited due to incomplete understanding of LM pathobiology. Expression of an activated beta2-adrenergic receptor has been described in LM tissue, suggesting that this pathway may contribute to the clinical manifestations of LM. We hypothesized that propranolol, a beta-adrenergic receptor antagonist, might improve symptoms of patients with LMs and lymphatic anomalies. A retrospective chart review of patients treated with propranolol as an adjunct therapy was conducted; analyses included demographic characteristics, clinical features, and response to propranolol. Three patients with cystic and noncystic LMs displayed clinical improvement at a minimum dose of 0.7 mg/kg/d, whereas symptomatic relapses were observed when propranolol doses dropped below this threshold. Two patients with Klippel-Trenaunay syndrome demonstrated partial clinical responses with reduced edema. The fetus of a mother treated with propranolol from a gestational age of 35 weeks through delivery displayed arrested growth of a cervicofacial LM. Our retrospective review suggests that propranolol improved symptoms in a subset of patients with lymphatic anomalies. Propranolol treatment may also limit the growth of congenital LMs in utero. PMID- 27561731 TI - Kinetics and mechanisms of formation of earthy and musty odor compounds: Chloroanisoles during water chlorination. AB - Chloroanisoles are often reported as off-flavor compounds which produce an earthy and musty flavors and odors in drinking water. To improve understanding and ultimately minimize the formation of 2,4-dichloroanisole (2,4-DCA), 2,6 dichloroanisole (2,6-DCA) and 2,4,6-trichloroanisole (2,4,6-TCA), which have low odor threshold concentrations (OTC: 0.03-4 ng L(-1)), a kinetic database for the chlorination of anisole was established by kinetic measurements. The results showed that HOCl reacted with anisole in acidic solution, with the hydrogen ion as an important catalyst. Quantification of product distribution of the produced chloroanisoles demonstrated that a chlorine attack in the para-position was favored over the ortho-position. A kinetic model was formulated, which permitted investigation of the relative importance of the chlorine dose and other water quality parameters including the concentrations of anisole and several metal ions, as well as temperature, on the product distribution of chloroanisoles. In general, high chlorine doses led to low concentrations of intermediates. The presence of ions such as Fe(3+) and Al(3+) facilitated the formation of chloroanisoles, but Zn(2+) and Mn(2+) did not. The kinetic model can be applied to optimize water chlorination and minimize earthy and musty odors. PMID- 27561732 TI - Predicting anti-androgenic activity of bisphenols using molecular docking and quantitative structure-activity relationships. AB - Both in vivo and in vitro assay indicated that bisphenols can inhibit the androgen receptor. However, the underlying antagonistic mechanism is unclear. In this study, molecular docking was employed to probe the interaction mechanism between bisphenols and human androgen receptor (hAR). The binding pattern of ligands in hAR crystal structures was also analyzed. Results show that hydrogen bonding and hydrophobic interactions are the dominant interactions between the ligands and hAR. The critical amino acid residues involved in forming hydrogen bonding between bisphenols and hAR is Asn 705 and Gln 711. Furthermore, appropriate molecular structural descriptors were selected to characterize the non-bonded interactions. Stepwise multiple linear regressions (MLR) analysis was employed to develop quantitative structure-activity relationship (QSAR) models for predicting the anti-androgenic activity of bisphenols. Based on the QSAR development and validation guideline issued by OECD, the goodness-of-fit, robustness and predictive ability of constructed QSAR model were assessed. The model application domain was characterized by the Euclidean distance and Williams plot. The mechanisms of the constructed model were also interpreted based on the selected molecular descriptors i.e. the number of hydroxyl groups (nROH), the most positive values of the molecular surface potential (Vs,max) and the lowest unoccupied molecular orbital energy (ELUMO). Finally, based on the model developed, the data gap for other twenty-six bisphenols on their anti-androgenic activity was filled. The predicted results indicated that the anti-androgenic activity of seven bisphenols was higher than that of bisphenol A. PMID- 27561733 TI - Relapse risk after autologous stem cell transplantation in patients with lymphoma based on CD34+ cell dose. AB - It is unclear whether higher CD34 + cell doses infused for ASCT have any influence on survival or relapse in patients with lymphoma. We analyzed the correlation of infused CD34 + cell dose with relapse, survival, and hematopoietic recovery in 146 consecutive patients undergoing ASCT for lymphoma. Higher doses (>5 * 106/kg) were significantly correlated with earlier hematopoietic recovery, fewer infectious episodes, lower transfusion needs. No differences were observed in lymphoma outcomes (4-year relapse incidence of 38% [95%CI: 29%-48%] in the lower dose group versus 51% [95%CI: 30%-69%] in the higher dose group, 10-year OS probabilities of 58% [95%CI: 48%-68%] versus 75% [95%CI: 59%-91%], 10-year DFS probabilities of 47% [95%CI: 37%-57%] versus 42% [95%CI: 23%-61%], p = NS for all outcomes). In this series, a higher infused CD34 + cell dose did not correlate with survival or relapse but correlated with earlier hematopoietic recovery and lower resource consumption. PMID- 27561734 TI - Isolating tape method is useful for an early judgment of curability during pancreaticoduodenectomy for pancreatic cancer. AB - Positive surgical margin of extrapancreatic nerve plexus (ENP) is a major cause of non-curative resection during pancreaticoduodenectomy (PD) for periampullary carcinoma (PC), which is difficult to detect at the early stage of PD. We describe a novel surgical technique using an isolating tape (iTape)-oriented ENP first dissection (IOEFD) during PD. The iTape is firstly passed through the retroperitoneal space between ENP and inferior vena cava. Then, the iTape is further extracted from major vessels such as the common hepatic and superior mesenteric artery. Consequently, the iTape encircles ENP alone. By tugging both ends of the iTape and vessel tapes to various directions from the caudal and cranial side of the pancreas, ENP is individually dissected without dividing any organ or tissue. Ten patients with periampullary carcinomas, consisting of one distal bile duct carcinoma, four ampullary carcinomas and five pancreatic head carcinomas underwent IOEFD during PD. Among these, nine underwent PDs after confirming negative surgical margin of ENP by IOEFD, while in the other case, PD was abandoned and converted to digestive bypass because of positive ENP margin during IOEFD. By final pathological diagnosis, R0 resection has been established in all nine patients who underwent PD with IOEFDs. Our pilot study indicated that inappropriate non-curative resection can be avoided by IOEFD during PD. PMID- 27561735 TI - How Primary Care Physicians Integrate Price Information into Clinical Decision Making. AB - BACKGROUND: Little is known about how primary care physicians (PCPs) in routine outpatient practice use paid price information (i.e., the amount that insurers finally pay providers) in daily clinical practice. OBJECTIVE: To describe the experiences of PCPs who have had paid price information on tests and procedures for at least 1 year. DESIGN: Cross-sectional study using semi-structured interviews and the constant comparative method of qualitative analysis. PARTICIPANTS: Forty-six PCPs within an accountable care organization. INTERVENTION: Via the ordering screen of their electronic health record, PCPs were presented with the median paid price for commonly ordered tests and procedures (e.g., blood tests, x-rays, CTs, MRIs). APPROACH: We asked PCPs for (a) their "gut reaction" to having paid price information, (b) the situations in which they used price information in clinical decision-making separate from or jointly with patients, (c) their thoughts on who bore the chief responsibility for discussing price information with patients, and (d) suggestions for improving physician-targeted price information interventions. KEY RESULTS: Among "gut reactions" that ranged from positive to negative, all PCPs were more interested in having patient-specific price information than paid prices from the practice perspective. PCPs described that when patients' out-of-pocket spending concerns were revealed, price information helped them engage patients in conversations about how to alter treatment plans to make them more affordable. PCPs stated that having price information only slightly altered their test-ordering patterns and that they avoided mentioning prices when advising patients against unnecessary testing. Most PCPs asserted that physicians bear the chief responsibility for discussing prices with patients because of their clinical knowledge and relationships with patients. They wished for help from patients, practices, health plans, and society in order to support price transparency in healthcare. CONCLUSIONS: Physician-targeted price transparency efforts may provide PCPs with the information they need to respond to patients' concerns regarding out-of pocket affordability rather than that needed to change test-ordering habits. PMID- 27561737 TI - The sketch is blank: No evidence for an explanatory role for cultural group selection. AB - As evidence that cultural group selection has occurred, Richerson et al. simply retrodict that humans use language, punish each other, and have religion. This is a meager empirical haul after 30 years. This contrasts sharply with the adaptationist approach to human behavior - evolutionary psychology - which has produced scores of novel, specific, and empirically confirmed predictions. PMID- 27561736 TI - Functional brain networks related to individual differences in human intelligence at rest. AB - Intelligence is a fundamental ability that sets humans apart from other animal species. Despite its importance in defining human behaviour, the neural networks responsible for intelligence are not well understood. The dominant view from neuroimaging work suggests that intelligent performance on a range of tasks is underpinned by segregated interactions in a fronto-parietal network of brain regions. Here we asked whether fronto-parietal interactions associated with intelligence are ubiquitous, or emerge from more widespread associations in a task-free context. First we undertook an exploratory mapping of the existing literature on functional connectivity associated with intelligence. Next, to empirically test hypotheses derived from the exploratory mapping, we performed network analyses in a cohort of 317 unrelated participants from the Human Connectome Project. Our results revealed a novel contribution of across-network interactions between default-mode and fronto-parietal networks to individual differences in intelligence at rest. Specifically, we found that greater connectivity in the resting state was associated with higher intelligence scores. Our findings highlight the need to broaden the dominant fronto-parietal conceptualisation of intelligence to encompass more complex and context-specific network dynamics. PMID- 27561738 TI - On a problematic procedure to manipulate response biases in recognition experiments: the case of "implied" base rates. AB - The experimental manipulation of response biases in recognition-memory tests is an important means for testing recognition models and for estimating their parameters. The textbook manipulations for binary-response formats either vary the payoff scheme or the base rate of targets in the recognition test, with the latter being the more frequently applied procedure. However, some published studies reverted to implying different base rates by instruction rather than actually changing them. Aside from unnecessarily deceiving participants, this procedure may lead to cognitive conflicts that prompt response strategies unknown to the experimenter. To test our objection, implied base rates were compared to actual base rates in a recognition experiment followed by a post-experimental interview to assess participants' response strategies. The behavioural data show that recognition-memory performance was estimated to be lower in the implied base rate condition. The interview data demonstrate that participants used various second-order response strategies that jeopardise the interpretability of the recognition data. We thus advice researchers against substituting actual base rates with implied base rates. PMID- 27561739 TI - Spinal cord diffusion tensor imaging in patients with sensory neuronopathy. AB - INTRODUCTION: We investigated whether MR diffusion tensor imaging (DTI) analysis of the cervical spinal cord could aid the (differential) diagnosis of sensory neuronopathies, an underdiagnosed group of diseases of the peripheral nervous system. METHODS: We obtained spinal cord DTI and T2WI at 3 T from 28 patients, 14 diabetic subjects with sensory-motor distal polyneuropathy, and 20 healthy controls. We quantified DTI-based parameters and looked at the hyperintense T2W signal at the spinal cord posterior columns. Fractional anisotropy and mean diffusivity values at C2-C3 and C3-C4 levels were compared between groups. We also compared average fractional anisotropy (mean of values at C2-C3 and C3-C4 levels). A receiver operating characteristic (ROC) curve was used to determine diagnostic accuracy of average fractional anisotropy, and we compared its sensitivity against the hyperintense signal in segregating patients from the other subjects. RESULTS: Mean age and disease duration were 52 +/- 10 and 11.4 +/ 9.3 years in the patient group. Eighteen subjects had idiopathic disease and 6 dysimmune etiology. Fractional anisotropy at C3-C4 level and average fractional anisotropy were significantly different between patients and healthy controls (p < 0.001 and <0.001) and between patients and diabetic subjects (p = 0.019 and 0.027). Average fractional anisotropy presented an area under the curve of 0.838. Moreover, it had higher sensitivity than visual detection of the hyperintense signal (0.86 vs. 0.54), particularly for patients with short disease duration. CONCLUSION: DTI-based analysis enables in vivo detection of posterior column damage in sensory neuronopathy patients and is a useful diagnostic test for this condition. It also helps the differential diagnosis between sensory neuronopathy and distal polyneuropathies. PMID- 27561740 TI - Integrating haplotype-specific linkage maps in tetraploid species using SNP markers. AB - KEY MESSAGE: Linkage mapping can help unravel the complexities of polyploid genomes. Here, we integrate haplotype-specific linkage maps in autotetraploid potato and explore the possibilities for mapping in other polyploid species. High density linkage mapping in autopolyploid species has become possible in recent years given the increasing number of molecular markers now available through modern genotyping platforms. Such maps along with larger experimental populations are needed before we can obtain sufficient accuracy to make marker-trait association studies useful in practice. Here, we describe a method to create genetic linkage maps for an autotetraploid species with large numbers of markers and apply it to an F1 population of tetraploid potato (Solanum tuberosum L.) of 235 individuals genotyped using a 20K SNP array. SNP intensity values were converted to allele dosages after which we calculated pairwise maximum likelihood estimates of recombination frequencies between all marker segregation types under the assumption of random bivalent pairing. These estimates were used in the clustering of markers into linkage groups and their subsequent ordering into 96 homologue maps. The homologue maps were integrated per chromosome, resulting in a total map length of 1061 cM from 6910 markers covering all 12 potato chromosomes. We examined the questions of marker phasing and binning and propose optimal strategies for both. We also investigated the effect of quadrivalent formation and preferential pairing on recombination frequency estimation and marker phasing, which is of great relevance not only for potato but also for genetic studies in other tetraploid species for which the meiotic pairing behaviour is less well understood. PMID- 27561741 TI - Case report: a common trunk of the coronary arteries. AB - We describe the heart from a 79-year-old woman with no medical history of cardiac complaints. Her heart shows a regular right coronary artery (RCA) and a variant left coronary artery (LCA) arising from the right sinus of Valsalva. The common stem of the RCA and the LCA is extremely short. The LCA depicts a preinfundibular course with a cranial-anterior loop and reaches the intersection of the anterior interventricular sulcus and the left coronary sulcus, where it divides into the regular branches, the anterior interventricular branch (left anterior descending, LAD) and the circumflex branch (left circumflex, LCx). All further branching resembles a normal distribution with the posterior interventricular branch coming for the RCA. Such a variant LCA is extremely rare with a reported incidence of 0.17 %. However, recognition and angiographic demonstration of such a variation assume the highest priority in a patient undergoing, for instance, direct coronary artery surgery or prosthetic valve replacement. PMID- 27561742 TI - Functional modulation on macrophage by low dose naltrexone (LDN). AB - Previously it was confirmed that naltrexone, a non-peptide delta-opioid receptor selective antagonist is mainly used for alcoholic dependence and opioid addiction treatment. However, there is increasing data on immune regulation of low dose naltrexone (LDN). The aim of this work was to explore the effect of LDN on the phenotype and function of macrophage. The changes of macrophage after treatment with LDN were examined using flow cytometry (FCM); FITC-dextran phagocytosis and enzyme-linked immunosorbent assay (ELISA). We have found that LDN enhances function of macrophage as confirmed by up-regulating MHC II molecule and CD64 on macrophage while down-regulating CD206 expression. Furthermore the productions of TNF-alpha, IL-6, IL-1beta, increased significantly. Macrophages in LDN treated group performed the enhanced phagocytosis. Therefore it is concluded that LDN could promote function of macrophage and this work has provided concrete data of impact on immune system by LDN. Especially the data would support interaction between CD4+T cell and macrophage in AIDS treatment with LDN in Africa (LDN has already been approved in Nigeria for the use in AIDS treatment). PMID- 27561743 TI - Risk Factors for Concordance Between Partners in Assault Among University Student Couples. AB - Based on information 11,408 university students provided on perpetration of physical assault in a romantic relationship, they were classified into three Dyadic Concordance Types (DCTs). We then examined six risk factors drawn from previous literature of partner violence: physical abuse as a child, antisocial personality characteristics, alcohol abuse, coercive control, chronic denigration in a relationship, and patriarchy at the societal level. We hypothesized that some risk factors for assault are different dependent on the DCT. Using multinomial logistic regression, we found that some risk factors were associated with an increase in the risk of a couple being in the Male Only assaulted DCT more than the other two DCTs (e.g., men who were high in antisocial personality characteristics). Other risk factors were found to be associated with a greater increase in the risk a couple being in the Both assaulted DCTs (e.g., chronic denigration). These results suggest that theories about the etiology of partner violence should take into account whether the couple is Male Only, Female Only, and Both assaulted. Identification of the DCTs of cases can be helpful in focusing research, treatment, and prevention of partner violence in a way that better reflects the actual situation. PMID- 27561744 TI - The Operational Challenges for Batterer Intervention Programs: Results From a 2 Year Study. AB - Batterers intervention programs (BIPs) constitute a primary intervention for perpetrators of intimate partner violence (IPV). There is little understanding as to what operational, or program-level, challenges BIPs face that can impede their effectiveness and adherence to state standards. As part of a 2-year ethnographic study, we conducted 36 individual semistructured interviews with professionals working with BIPs and identified five themes related to program-level challenges for BIPs: (a) information barriers, (b) safety issues, (c) facilitator retention and training, (d) the need for monitoring, and (e) funding constraints. We conclude that continued work needs to be done at both the state and local level, and in coordination with community judicial, mental health, human services, and other agencies to help provide resources that support BIPs in sustained, safe, and as effective as possible work. PMID- 27561745 TI - Relationships Among Dispositional Mindfulness, Distress Tolerance, and Women's Dating Violence Perpetration: A Path Analysis. AB - Scant research examined mechanisms underlying the relationship between dispositional mindfulness and dating violence (DV) perpetration. Using a cross sectional design with 203 college women, we examined whether distress tolerance mediated the relationship between dispositional mindfulness and DV perpetration (i.e., psychological aggression and physical assault). Path analyses results revealed indirect effects of mindfulness facets nonjudging of inner experiences and nonreactivity to inner experiences on both psychological aggression and physical assault through distress tolerance. Mindfulness facets observing, describing, and acting with awareness were not linked to DV perpetration through distress tolerance. Results suggest that women who allow internal experiences to come and go without assigning criticism or avoidance are better able to tolerate transient distress and less likely to abuse a dating partner. Future research may examine distress tolerance and dispositional mindfulness facets as potential intervention targets for women who abuse dating partners. PMID- 27561746 TI - Religious Affiliation, Religiosity, Gender, and Rape Myth Acceptance: Feminist Theory and Rape Culture. AB - Rape myths are false beliefs about rape, rape victims, and rapists, often prejudicial and stereotypical. Guided by feminist theory and available empirical research, this study aimed to examine the influences of gender, religious affiliation, and religiosity on rape myth acceptance of U.S. emerging adults. A sample of 653 university students aged 18 to 30 years were recruited from a large public university in the southern United States to complete the research questionnaires. Results indicated that individuals who identified as Roman Catholic or Protestant endorsed higher levels of rape myth acceptance than their atheist or agnostic counterparts. Men were found more likely to ascribe to rape myths than their female counterparts. Religiosity was positively associated with rape myth acceptance, even after controlling the effect of conservative political ideology. No significant interaction was found between gender and religious affiliation or gender and religiosity. Limitations, future research directions, and implications of the findings are discussed from the perspective of feminist theory. PMID- 27561747 TI - Overgrowth of Silver Nanodisks on a Substrate into Vertically Aligned Nanopillars for Chromatic Light Polarization. AB - Vertically aligned and well-separated 1D silver nanopillars (AgNPLs) are prepared on a large-area quartz surface using a robust colloidal chemical technique. Silver nanodisk (AgND) monolayers were first deposited on quartz using the Langmuir-Blodgett technique, and the presence of the substrate induced asymmetric chemical overgrowth of the AgNDs into AgNPLs. The height and diameter of the prepared AgNPLs were controlled by changing the rate of the overgrowth reaction. Chloride ions were used during overgrowth to etch the silver atoms that formed sharp features on the sides of the AgNDs and to limit growth in the lateral direction. The grown AgNPLs displayed two surface plasmon resonance modes corresponding to the transverse and longitudinal electron oscillations. The intensity of the longitudinal mode increased by a factor of 9 while the intensity of the transverse mode decreased by a factor of 2.5 upon increasing the angle of incidence of the exciting light from 0 degrees to 60 degrees . This interesting property makes these AgNPL arrays on quartz useful as chromatic light polarizers. PMID- 27561750 TI - Ultrasociality, class, threat, and intentionality in human society. AB - Gowdy & Krall neglect an important aspect of human societies, which is that class systems are not genetically based but rather based on threat. In turn, threat presupposes intentionality, so seems to distinguish human from arthropod ultrasociality. Class systems, in turn, seem to explain the distinctive mixture of persistence and instability characteristic of human, but not arthropod, ultrasocial populations. PMID- 27561748 TI - Refractive results of phacoemulsification in vitrectomized patients. AB - The aim of this study was to compare the refractive errors after uneventful phacoemulsification and intraocular lens implantation in the cases of vitrectomized eyes and non-vitrectomized eyes. Vitrectomized eyes were divided into 2 groups: vitrectomy alone as Group 1, vitrectomy with gas tamponade as Group 2. Normal-controlled eyes were categorized as Group 3. Intraocular lens (IOL) power calculation and the measurements of axial length (AL) and keratometric value (K) were performed using the IOLMaster and the Haigis and SRK/T formula as subgroup A and B. The measurements of AL, K, and IOL power calculation were also performed by the applanation ultrasound and the SRK/T formula as comparison subgroup C. The mean numeric error (MNE) and median absolute error (MedAE) were compared between Groups and subgroups. The MedAE was not significantly different in Group 1A, 2A, and 3A, respectively (p > 0.05). The MNE was significantly different in Group 1A, 2A, and 3A (p = 0.04). Post hoc test showed an insignificant difference between Group 1A and 3A (p = 0.36), but significantly a higher MNE in Group 2A than that in Group 3A (p = 0.03). A significantly longer AL was noted in Group 1B and 2B, comparing with Group 1C and 2C (p < 0.01). Refractive outcomes after phacoemulsification sequential to vitrectomy alone were comparable to those in normal control. Hyperopic shift was found following phacoemulsification sequential to vitrectomy with gas tamponade comparing to normal eyes. A significantly longer AL was found using optical biometry compared to applanation ultrasound in vitrectomized eyes, but not in normal eyes. PMID- 27561749 TI - FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post Myocardial Infarction Rats. AB - Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects. Exercise improved the functional performance, reduced fibrosis of MI-hearts and induced FSTL1 expression, the TGFbeta-Smad2/3 signaling and angiogenesis in myocardium. In gastrocnemius, exercise increased the cross sectional area of myocytes and FSTL1 expression. Importantly, exercise increased circulating FSTL1 levels, which were positively correlated with the skeletal muscle FSTL1 expression and negatively correlated with heart fibrosis. Overall, the IAE was more effective than that of MVT in cardioprotection. Finally, exogenous FSTL1 administration directly improved angiogenesis as well as functionality of post-MI hearts. Taken together, we have demonstrated that FSTL1 is a potential mediator of exercise-induced cardioprotection in post-MI rats. PMID- 27561751 TI - Imaging Informatics Finally Breaks into the Enterprise. PMID- 27561752 TI - Method for Adapting the Grayscale Standard Display Function to the Aging Eye. AB - Perceptual linearity of grayscale images based on a contrast sensitivity model is a widely recognized and used standard for medical imaging visualization. This approach ensures consistency across devices and provides perception of luminance variations in direct relationship to changes in image values. We analyze the effect of aging of the human eye on the precept of linearity and demonstrate that not only the number of just-noticeable differences diminishes for older subjects but also linearity across the range of luminance values is significantly affected. While loss of JNDs is inevitable for a fixed luminance range, our findings suggest possible corrective approaches for maintaining linearity. PMID- 27561754 TI - A Multimodal Search Engine for Medical Imaging Studies. AB - The use of digital medical imaging systems in healthcare institutions has increased significantly, and the large amounts of data in these systems have led to the conception of powerful support tools: recent studies on content-based image retrieval (CBIR) and multimodal information retrieval in the field hold great potential in decision support, as well as for addressing multiple challenges in healthcare systems, such as computer-aided diagnosis (CAD). However, the subject is still under heavy research, and very few solutions have become part of Picture Archiving and Communication Systems (PACS) in hospitals and clinics. This paper proposes an extensible platform for multimodal medical image retrieval, integrated in an open-source PACS software with profile-based CBIR capabilities. In this article, we detail a technical approach to the problem by describing its main architecture and each sub-component, as well as the available web interfaces and the multimodal query techniques applied. Finally, we assess our implementation of the engine with computational performance benchmarks. PMID- 27561753 TI - Crypto-Watermarking of Transmitted Medical Images. AB - Telemedicine is a booming healthcare practice that has facilitated the exchange of medical data and expertise between healthcare entities. However, the widespread use of telemedicine applications requires a secured scheme to guarantee confidentiality and verify authenticity and integrity of exchanged medical data. In this paper, we describe a region-based, crypto-watermarking algorithm capable of providing confidentiality, authenticity, and integrity for medical images of different modalities. The proposed algorithm provides authenticity by embedding robust watermarks in images' region of non-interest using SVD in the DWT domain. Integrity is provided in two levels: strict integrity implemented by a cryptographic hash watermark, and content-based integrity implemented by a symmetric encryption-based tamper localization scheme. Confidentiality is achieved as a byproduct of hiding patient's data in the image. Performance of the algorithm was evaluated with respect to imperceptibility, robustness, capacity, and tamper localization, using different medical images. The results showed the effectiveness of the algorithm in providing security for telemedicine applications. PMID- 27561755 TI - Becoming an expert: Ontogeny of expertise as an example of neural reuse. AB - In this commentary, we discuss an important pattern of results in the literature on the neural basis of expertise: (a) decrease of cerebral activation at the beginning of acquisition of expertise and (b) functional cerebral reorganization as a consequence of years of practice. We show how these two results can be integrated with the neural reuse framework. PMID- 27561756 TI - Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons. AB - The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (>=0.6 IU L-1 ). In the retrospective population, post gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, 20%) while in MtFs post-gonadectomy levels and baseline levels were comparable ( 6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs. PMID- 27561757 TI - Review of fertility preservation issues for young women with breast cancer. AB - It is well documented that cancer treatment may temporarily or permanently impair childbearing potential of young women with breast cancer. Given that many patients have not initiated or completed their families when diagnosed, fertility issues are of utmost importance in this clinical population. This review addresses the importance of incorporating fertility issues into the clinical care of young breast cancer patients, focusing on recent knowledge and counselling practices about fertility-related issues and the complexity of fertility-related decisions in this population. Multiple studies report cancer-related infertility may have serious psychological consequences and reduce Quality of Life for some patients. To guide health care providers and patients regarding appropriate, safe, and cost-effective fertility care for women who desire biological children, several professional organizations have developed clinical practice guidelines. However, the extent to which health professionals use these guidelines and provide timely and appropriate fertility-related information to patients is questionable. Fertility should not be neglected by health care providers and a multidisciplinary team is needed to target fertility issues at diagnosis and into survivorship care, providing timely, clear information that includes support, resources, and appropriate referral to fertility specialists. This information will assist in making well-informed decisions about fertility after breast cancer. PMID- 27561759 TI - A new phthalide derivative from Peperomia nivalis. AB - One new phthalide (1) was isolated from aerial parts of Peperomia nivalis, along with known compounds (2 and 3), reported in this species for the first time. The structure of the new compound was characterised on the basis of 1D (1H and 13C NMR), 2D (COSY, HMQC, HMBC and NOESY) NMR and high-resolution mass spectral (HRMS) data. Compound 2 was isolated from a natural source for the first time but previously synthesised. Compounds 1-3 were evaluated for their anti-Helicobacter pylori and anti-Plasmodium falciparum activities. Compound 1 showed moderate activities against H. pylori (MIC 47.5 MUM) and the F32-Tanzania strain of P. falciparum (IC50 8.5 MUM). Compounds 2 and 3 exhibited weak anti-H. pylori activity (MIC 241.3 and 237.6 MUM, respectively) and were inactive against P. falciparum. PMID- 27561760 TI - A Simple Disease-Guided Approach to Personalize ACC/AHA-Recommended Statin Allocation in Elderly People: The BioImage Study. AB - BACKGROUND: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with >=7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone. OBJECTIVES: This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis. METHODS: In 5,805 BioImage participants without known ASCVD at baseline, those with >=7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was >=100 (or equivalent cPB). RESULTS: At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0. CONCLUSIONS: Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice. PMID- 27561758 TI - Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance. AB - Cancer stem cells (CSCs) are a small subpopulation of tumor cells with capabilities of self-renewal, dedifferentiation, tumorigenicity, and inherent chemo-and-radio therapy resistance. Tumor resistance is believed to be caused by CSCs that are intrinsically challenging to common treatments. A number of CSC markers including CD44, CD133, receptor tyrosine kinase, aldehyde dehydrogenases, epithelial cell adhesion molecule/epithelial specific antigen, and ATP-binding cassette subfamily G member 2 have been proved as the useful targets for defining CSC population in solid tumors. Furthermore, targeting CSC markers through new therapeutic strategies will ultimately improve treatments and overcome cancer drug resistance. Therefore, the identification of novel strategies to increase sensitivity of CSC markers has major clinical implications. This review will focus on the innovative treatment methods such as nano-, immuno-, gene-, and chemotherapy approaches for targeting CSC-specific markers and/or their associated signaling pathways. PMID- 27561761 TI - Risk Statins or Risk "Zero" on Atherosclerosis Imaging for Risk Stratification? PMID- 27561762 TI - Outcomes of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention. AB - BACKGROUND: Atrial fibrillation (AF) is increasing in prevalence, and patients with a history of AF commonly undergo percutaneous coronary intervention (PCI). There is a paucity of contemporary data on the association between AF and clinical outcomes after PCI. OBJECTIVES: The study sought to evaluate the association between AF and in-hospital adverse outcomes using a large, prospective multicenter registry. METHODS: Data for consecutive PCI cases from 47 hospitals performed between April 2011 and December 2014 were utilized for the analysis. Propensity-matched multivariate analysis was used to adjust for differences in baseline characteristics between patients with and without a history of AF. RESULTS: Of 113,283 PCI cases during the study period, a history of AF was present in 13,912 patients (12%), which varied by institution (range 2.5% to 18.4%). At baseline, patients with a history of AF were older and were more likely to have comorbid congestive heart failure, cardiomyopathy, cerebrovascular disease, and chronic lung disease. Patients with a history of AF were more likely to have in-hospital complications, including in-hospital mortality (3% vs. 1%). In propensity-matched analysis, patients with a history of AF were more likely to be treated with a bare-metal stent (27% vs. 18%). In the propensity-matched model, AF remained independently associated with an increased risk of developing post-procedural bleeding (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.15 to 1.52), heart failure (OR: 1.33; 95% CI: 1.17 to 1.52), cardiogenic shock (OR: 1.26; 95% CI: 1.08 to 1.48), and in-hospital mortality (OR: 1.41; 95% CI: 1.18 to 1.68). CONCLUSIONS: AF is common among patients undergoing PCI. AF is associated with older age, the presence of other comorbidities, and independently associated with in-hospital post-procedural heart failure, cardiogenic shock, and mortality. PMID- 27561763 TI - A Fresh Perspective on Atrial Fibrillation. PMID- 27561764 TI - Wait-List Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation in the U.S. AB - BACKGROUND: Heart failure represents a common end-stage syndrome for many adults with congenital heart disease (ACHD). These patients, however, have been excluded from most heart transplantation research. It is not known how current criteria, derived from non-ACHD populations, used to determine priority at the time of transplant listing, impact the outcomes for ACHD patients listed for heart transplantation. OBJECTIVES: The goal of this study was to investigate outcomes of ACHD in comparison to non-ACHD patients while listed for heart transplantation. METHODS: We conducted a retrospective study using the Scientific Registry of Transplant Recipients on patients >=18 years of age listed in the United States between 1999 and 2014. The probability of mortality or delisting due to clinical worsening was estimated using cumulative incidence functions, where transplantation was a competing event. RESULTS: Among 1,290 ACHD and 38,557 non-ACHD patients listed, 237 ACHD and 6,377 non-ACHD patients died or were delisted due to clinical worsening. Death or delisting for clinical worsening was more likely for ACHD patients initially listed as status 1A (24% ACHD vs. 17% non ACHD after 180 days; p < 0.001). There were no significant differences between ACHD and non-ACHD patients listed as status 1B or 2. In multivariable analysis, factors associated with death or delisting due to clinical worsening within 1 year in ACHD included: estimated glomerular filtration rate <60 ml/min/1.73 m(2) (hazard ratio [HR]: 1.4; 95% confidence interval [CI]: 1.0 to 1.9; p = 0.043); albumin <3.2 g/dl (HR: 2.0; 95% CI: 1.3 to 2.9; p <0.001); and hospitalization at the time of listing, whether in the intensive care unit (HR: 2.3; 95% CI: 1.6 to 3.5; p < 0.001) or not (HR: 1.9; 95% CI: 1.2 to 3.0; p = 0.006) relative to outpatients. CONCLUSIONS: Wait-list mortality or delisting due to worsening clinical status is disproportionately common for ACHD patients listed as status 1A. An allocation system that takes into account the distinctive aspects of ACHD patients may help better care for this growing population. PMID- 27561765 TI - Fitting Heart Transplantation to Adults With Congenital Heart Disease: Square Peg in a Round Hole? PMID- 27561766 TI - Discordances Between Pre-Natal and Post-Natal Diagnoses of Congenital Heart Diseases and Impact on Care Strategies. AB - BACKGROUND: Pre-natal diagnosis of congenital heart disease (CHD) allows anticipation of urgent neonatal treatment and provides adequate information to the parents on cardiac outcomes. OBJECTIVES: This study sought to analyze the discordances between expert fetal cardiac diagnosis and final diagnosis of CHD and their impact on neonatal and long-term care strategies. METHODS: We included 1,258 neonates with a pre-natally diagnosed CHD and 189 fetopsies following termination of pregnancy at our tertiary center over a 10-year period. Pre-natal echocardiographic and final diagnoses were compared. RESULTS: For live births, we identified 368 (29.3%) discordances between pre- and post-natal diagnoses. The pre-natal diagnosis was different from the post-natal diagnosis in 36 cases (2.9%) and partially different with a major impact on neonatal treatment of the CHD in 97 cases (7.7%). In 235 cases (18.7%), the diagnosis was partially different with no impact on neonatal planned treatment. The discordances had a negative impact on late care strategy in 62 cases (4.9%): more complex CHD that was unsuitable for biventricular repair, leading to unplanned compassionate care, additional surgery or increase of the complexity level of the Aristotle score. A positive impact was found in 31 cases (2.5%): less complex CHD that allowed biventricular repair, fewer surgical procedures, or decrease of the complexity of the Aristotle score. For 275 patients (21.9%), there was no impact on late care strategy. Of the 872 terminations of pregnancy and intrauterine fetal deaths, 189 fetopsies were available: 16 (8.5%) different diagnoses, 27 (14.3%) major differences, and 60 (31.7%) minor differences. CONCLUSIONS: Correcting fetal cardiac diagnosis after birth can lead to significant changes in neonatal (10.6%) and late (7.4%) care strategies. Tools should be developed to try to improve the accuracy of pre-natal diagnosis of CHD. Clinicians should be cautious when predicting required treatment and outcomes during pre-natal counseling. PMID- 27561767 TI - Discordant Fetal and Post-Natal Diagnosis: Can We Do Better? PMID- 27561769 TI - Cystatin C and Cardiovascular Disease: Causality, Association, and Clinical Implications of Knowing the Difference. PMID- 27561770 TI - Left Ventricular Noncompaction: A Distinct Genetic Cardiomyopathy? AB - Left ventricular noncompaction (LVNC) describes a ventricular wall anatomy characterized by prominent left ventricular (LV) trabeculae, a thin compacted layer, and deep intertrabecular recesses. Individual variability is extreme, and trabeculae represent a sort of individual "cardioprinting." By itself, the diagnosis of LVNC does not coincide with that of a "cardiomyopathy" because it can be observed in healthy subjects with normal LV size and function, and it can be acquired and is reversible. Rarely, LVNC is intrinsically part of a cardiomyopathy; the paradigmatic examples are infantile tafazzinopathies. When associated with LV dilation and dysfunction, hypertrophy, or congenital heart disease, the genetic cause may overlap. The prevalence of LVNC in healthy athletes, its possible reversibility, and increasing diagnosis in healthy subjects suggests cautious use of the term LVNC cardiomyopathy, which describes the morphology but not the functional profile of the cardiomyopathy. PMID- 27561771 TI - Aspirin and Cancer. AB - The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10 year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies. PMID- 27561772 TI - The Potential Impact of Expanding Cardiac Rehabilitation in Heart Failure. PMID- 27561768 TI - Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study. AB - BACKGROUND: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS: We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS: Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 * 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 * 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 * 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. PMID- 27561773 TI - Sex Differences in Cardiac Troponin and the Risk of Death or Major Cardiovascular Events. PMID- 27561774 TI - High Risk of Gastrointestinal Bleeding on Dual Antiplatelet Treatment. PMID- 27561775 TI - Reply: High Risk of Gastrointestinal Bleeding on Dual Antiplatelet Treatment. PMID- 27561776 TI - Nonobstructive Hypertrophic Cardiomyopathy: Low Mortality but Not Always Benign. PMID- 27561777 TI - Reply: Nonobstructive Hypertrophic Cardiomyopathy: Low Mortality but Not Always Benign. PMID- 27561778 TI - Tight coupling of leaf area index to canopy nitrogen and phosphorus across heterogeneous tallgrass prairie communities. AB - Nitrogen (N) and phosphorus (P) are limiting nutrients for many plant communities worldwide. Foliar N and P along with leaf area are among the most important controls on photosynthesis and hence productivity. However, foliar N and P are typically assessed as species level traits, whereas productivity is often measured at the community scale. Here, we compared the community-level traits of leaf area index (LAI) to total foliar nitrogen (TFN) and total foliar phosphorus (TFP) across nearly three orders of magnitude LAI in grazed and ungrazed tallgrass prairie in north-eastern Kansas, USA. LAI was strongly correlated with both TFN and TFP across communities, and also within plant functional types (grass, forb, woody, and sedge) and grazing treatments (bison or cattle, and ungrazed). Across almost the entire range of LAI values and contrasting communities, TFN:TFP ratios indicated co-limitation by N and P in almost all communities; this may further indicate a community scale trend of an optimal N and P allocation per unit leaf area for growth. Previously, results from the arctic showed similar tight relationships between LAI:TFN, suggesting N is supplied to canopies to maximize photosynthesis per unit leaf area. This tight coupling between LAI, N, and P in tallgrass prairie suggests a process of optimal allocation of N and P, wherein LAI remains similarly constrained by N and P despite differences in species composition, grazing, and canopy density. PMID- 27561779 TI - Cold and alone? Roost choice and season affect torpor patterns in lesser short tailed bats. AB - Seasonal changes in weather and food availability differentially impact energy budgets of small mammals such as bats. While most thermal physiological research has focused on species that experience extreme seasonal temperature variations, knowledge is lacking from less variable temperate to subtropical climates. We quantified ambient temperature (T a) and skin temperature (T sk) responses by individuals from a population of New Zealand lesser short-tailed bats (Mystacina tuberculata) during summer and winter using temperature telemetry. During summer, communal roosts were more thermally stable than T a. During winter, solitary roosts were warmer than T a indicating significant thermal buffering. Communal roost trees were used on 83 % of observation days during summer, and individuals occupying them rarely entered torpor. Solitary roosts were occupied on 93 % of observation days during winter, and 100 % of individuals occupying them used torpor. During summer and winter, bats employed torpor on 11 and 95 % of observation days, respectively. Maximum torpor bout duration was 120.8 h and winter torpor bout duration correlated negatively with mean T a. Torpor bout duration did not differ between sexes, although female minimum T sk was significantly lower than males. The summer Heterothermy Index varied, and was also significantly affected by T a. Mean arousal time was correlated with sunset time and arousals occurred most frequently on significantly warmer evenings, which are likely associated with an increased probability of foraging success. We provide the first evidence that torpor is used flexibly throughout the year by M. tuberculata, demonstrating that roost choice and season impact torpor patterns. Our results add to the growing knowledge that even small changes in seasonal climate can have large effects on the energy balance of small mammals. PMID- 27561781 TI - Immune modulation enables a specialist insect to benefit from antibacterial withanolides in its host plant. AB - The development of novel plant chemical defenses and counter adaptations by herbivorous insect could continually drive speciation, producing more insect specialists than generalists. One approach to test this hypothesis is to compare closely related generalist and specialist species to reveal the associated costs and benefits of these different adaptive strategies. We use the specialized moth Heliothis subflexa, which feeds exclusively on plants in the genus Physalis, and its close generalist relative H. virescens. Specialization on Physalis plants necessitates the ability to tolerate withanolides, the secondary metabolites of Physalis species that are known to have feeding deterrent and immune inhibiting properties for other insects. Here we find that only H. subflexa benefits from the antibacterial properties of withanolides, and thereby gains a higher tolerance of the pathogen Bacillus thuringiensis. We argue that the specialization in H. subflexa has been guided to a large extent by a unique role of plant chemistry on ecological immunology. PMID- 27561780 TI - Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention deficit/hyperactivity disorder. AB - It has been suggested that neurotrophins are involved in the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate whether there are differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and neurotrophin-3 (NTF3) levels between children with ADHD and healthy controls. A total of 110 treatment-naive children with the combined presentation of ADHD and 44 healthy controls aged 8-18 years were enrolled in this study. The severity of ADHD symptoms was determined by scores on the Conners' Parent Rating Scale Revised Short and Conners' Teacher Rating Scale-Revised Short. The severity of depression and anxiety symptoms of the children were evaluated by the self-report inventories. Serum levels of neurotrophins were measured using commercial enzyme linked immunosorbent assay kits. The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the levels of serum neurotrophins, an effect that was independent of age, sex, and the severity of the depression and anxiety. The analysis of covariance (ANCOVA) indicated that the mean serum GDNF and NTF3 levels of ADHD patients were significantly higher than that of controls. However, serum BDNF and NGF levels did not show any significant differences between groups. No correlations between the levels of serum neurotrophins and the severity of ADHD were observed. These results suggest that elevated serum GDNF and NTF3 levels may be related to ADHD in children. PMID- 27561782 TI - D27E mutation of VTC1 impairs the interaction with CSN5B and enhances ascorbic acid biosynthesis and seedling growth in Arabidopsis. AB - Our previous investigation revealed that GDP-Man pyrophosphorylase (VTC1), a vital ascorbic acid (AsA) biosynthesis enzyme, could be degraded through interaction with the photomorphogenic factor COP9 signalosome subunit 5B (CSN5B) in the darkness, demonstrating the posttranscriptional regulation of light signal in AsA production. Here, we further report that a point mutation in D27E of VTC1 disables the interaction with CSN5B, resulting in enhancement of AsA biosynthesis and seedling growth in Arabidopsis thaliana. To identify the interaction sites with CSN5B, we first predicted the key amino acids in VTC1 via bioinformatics analysis. And then we biochemically and genetically demonstrated that the 27th Asp was the amino acid that influenced the interaction of VTC1 with CSN5B in plants. Moreover, transgenic lines overexpressing the site-specific mutagenesis from D27 (Asp) into E27 (Glu) in VTC1 showed enhanced AsA accumulation and reduced H2O2 content in Arabidopsis seedlings, compared with the lines overexpressing the mutation from D27 into N27 (Asn) in VTC1. In addition, this regulation of VTC1 D27E mutation promoted seedling growth. Together, our data reveal that the 27th amino acid of VTC1 confers a key regulation in the interaction with CSN5B and AsA biosynthesis, as well as in Arabidopsis seedling growth. PMID- 27561783 TI - Cloning and characterization of soybean gene Fg1 encoding flavonol 3-O glucoside/galactoside (1->6) glucosyltransferase. AB - KEY MESSAGE: Flavonoids are important secondary metabolites in plants. Sugar sugar glycosyltransferases are involved in the final step of flavonoid biosynthesis and contribute to the structural diversity of flavonoids. This manuscript describes the first cloning of a sugar-sugar glucosyltransferase gene in the UGT family that attaches glucose to the 6"-position of sugar bound to a flavonol. The results provide a glimpse on the possible evolution of sugar-sugar glycosyltransferase genes and identify putative amino acids responsible for the recognition of the hydroxyl group of the sugar moiety and specification of sugar. A scheme for the genetic control of flavonol glycoside biosynthesis is proposed. Flavonol glycosides (FGs) are predominant in soybean leaves and they show substantial differences among genotypes. In previous studies, we identified two flavonoid glycoside glycosyltransferase genes that segregated in recombinant inbred lines developed from a cross between cultivars Nezumisaya and Harosoy; one was responsible for the attachment of glucose to the 2"-position of glucose or galactose that is bound to the 3-position of kaempferol and the other was involved in the attachment of glucose to the 6"-position. This study was conducted to clone and characterize the 6"-glucosyltransferase gene. Linkage mapping indicated that the gene was located in the molecular linkage group I (chromosome 20). Based on the genome sequence, we cloned a candidate cDNA, GmF3G6"Gt from Harosoy but the corresponding cDNA could not be amplified by PCR from Nezumisaya. The coding region of GmF3G6"Gt in Harosoy is 1386 bp long encoding 462 amino acids. This gene was not expressed in leaves of Nezumisaya. The GmF3G6"Gt recombinant protein converted UDP-glucose and kaempferol 3-O glucoside or kaempferol 3-O-galactoside to kaempferol 3-O-glucosyl-(1->6) glucoside or kaempferol 3-O-glucosyl-(1->6)-galactoside, respectively. These results indicate that GmF3G6"Gt encodes a flavonol 3-O-glucoside/galactoside (1 >6) glucosyltransferase and corresponds to the Fg1 gene. GmF3G6"Gt had an amino acid similarity of 82 % with GmF3G6"Rt encoding flavonol 3-O glucoside/galactoside (1->6) rhamnosyltransferase, suggesting a recent evolutionary divergence of the two genes. This may be the first cloning of a sugar-sugar glucosyltransferase gene in the UGT family that attaches glucose to the 6"-position of sugar bound to a flavonol. A scheme for the control of FG biosynthesis is proposed. PMID- 27561784 TI - Mastitis associated with Sjogren's syndrome: a series of nine cases. AB - Sjogren's syndrome is well known to target exocrine glands, especially lacrimal and salivary glands, which share with mammary glands anatomical, histological, and immunological features. Herein, we investigated the mammary involvement in patients with Sjogren's syndrome and compared the histological findings with minor salivary gland involvement. We reviewed the charts of patients with Sjogren's syndrome (followed in Montpellier University Hospital, between January 2000 and January 2015), in whom minor salivary gland and mammary tissues were available. Two expert pathologists analysed retrospectively these tissues in order to identify inflammatory patterns. Immunohistochemical stainings were performed to precise leucocyte distribution. Sixteen Sjogren's syndrome patients with available salivary and breast tissue samples were included. All were women, with a median age of 60.1 +/- 11.3 years at Sjogren's syndrome diagnosis. Mammary biopsy was conducted because of breast symptoms in 6 patients and following imaging screening strategies for breast cancer in 10 patients. Nine patients exhibited an inflammatory breast pattern (lymphocytic infiltrates or duct ectasia), close to minor salivary gland histological findings. Immunohistochemical stainings (n = 5) revealed B and T cell infiltrates within breast tissue, with a higher proportion of T CD4+ cells, but no IgG4-secreting plasma cells were found. This is the first series to describe breast inflammatory patterns in Sjogren's syndrome. Mastitis is in line with the classical involvement of exocrine glands in this disease. These findings are consistent with the literature data considering Sjogren's syndrome as an "autoimmune epithelitis". PMID- 27561785 TI - Postural tachycardia syndrome (POTS) with anti-NMDA receptor antibodies after human papillomavirus vaccination. AB - We describe a young woman who developed POTS with positive serum anti-NMDA receptor antibodies and no evidence of encephalitis after vaccination with HPV vaccine, Cervarix. Her symptoms improved significantly with immunomodulatory therapy and re-occurred after immunomodulatory therapy was stopped, suggesting an autoimmune etiology of POTS after vaccination. PMID- 27561786 TI - Irregular antibodies in no hemolytic autoimmune diseases are able to induce erythrophagocytosis. AB - Irregular antibodies are produced by alloimmunization because of pregnancies or blood transfusions. They are called "irregular" due to target erythrocyte antigens from "rare blood systems," those different from the ABO system. Irregular antibodies have been widely investigated in immunohematology since their presence in blood donors may lead to difficulties in blood typing and in blood cross-matching, or to induce hemolytic transfusion reactions. Nevertheless, their incidence and participation in the physiopathology of autoimmune diseases have not been thoroughly studied. In this work, we analyzed the presence and pro hemolytic capabilities of irregular antibodies in patients with different autoimmune diseases lacking signs of hemolytic anemia, in comparison with healthy multiparous women. Five of 141 autoimmune patients (3.5 %) and two of 77 multiparous women (2.6 %) were positive. Although frequency was relatively low and similar in both populations, the targeted antigens were Kell (k, Kpb, Jsb) and Luth (Lub) in multiparous women, and the same plus Duffy (Fya), Kidd (Jka) and MNS (M, s) in autoimmune patients. Irregular antibodies from autoimmune patients did not induce complement-mediated hemolysis (intravascular), but they were able to induce macrophages-mediated phagocytosis (extravascular hemolysis) in vitro. It is the first approach exploring the presence of irregular antibodies associated with the loss of immune tolerance and demonstrating their hemolytic potential in autoimmune patients without hemolytic manifestations. The presence of irregular antibodies targeted to Duffy (Fya), Kidd (Jka) and MNS (M, s) antigens only in autoimmune patients suggests a loss of immune tolerance to these erythrocyte antigens. PMID- 27561788 TI - Role of environmental factors in autoimmunity: pearls from the 10th international Congress on autoimmunity, Leipzig, Germany 2016. PMID- 27561787 TI - Pulmonary hyalinizing granuloma: a multicenter study of 5 new cases and review of the 135 cases of the literature. AB - Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by single or multiple benign lung nodules mimicking lung neoplasma. Histologic analysis reveals homogenous hyaline lamellae, usually surrounded by collection of plasma cells, lymphocytes and histiocytes in a perivascular distribution. The clinical and radiological findings have been described in small series, but the long-term outcomes have rarely been reported. The objectives were to describe the clinical, radiological and outcomes of PHG in new cases and through a literature review. Patients with PHG were found by a multicenter search among French departments of internal medicine, pulmonology and anatomo-pathology. Review of the literature was made through the National Library of Medicine's MEDLINE database using keywords "hyalinizing granuloma." Five news cases and 135 cases of the literature were found. There were 82 men and 57 women, mean age at the diagnosis 44.6 years (15-83). Patients were frequently asymptomatic (n = 39, 27.4 %). The nodule was unique in 37 cases (28.9 %) and multiple in 91 cases (71.1 %). 18FDG PET scan revealed hypermetabolism of the nodule in 9/15 cases (60 %). A systemic disease was associated in 65 cases (mainly mediastinal and retroperitoneal fibrosis, autoimmune, tumoral or infectious disease or thromboembolism). The outcomes were evaluated in 73 patients when follow-up was available: 14 patients had a surgical resection of the nodule. Forty-five patients did not receive any immunosuppressive drug. Among these patients, 2 improved, 29 were stable and 14 worsened. Corticosteroids were used as a monotherapy in 19 patients and led to radiological improvement in 8 cases, stabilization in 8 cases and worsening in 3 cases. Five patients were treated with corticosteroids and at least one immunosuppressive drug and 4 patients improved. PHG is a rare benign disease, mimicking lung neoplasma, frequently associated with systemic diseases. PMID- 27561789 TI - Active modulation of visible light with graphene-loaded ultrathin metal plasmonic antennas. AB - Electro-optical modulation of visible and near-infrared light is important for a wide variety of applications, ranging from communications to sensing and smart windows. However, currently available approaches result in rather bulky devices, suffer from low integrability, and can hardly operate at the low power consumption levels and fast switching rates required by microelectronic drivers. Here we show that planar nanostructures patterned in ultrathin metal-graphene hybrid films sustain highly tunable plasmons in the visible and near-infrared spectral regions. Strong variations in the reflection and absorption of incident light take place when the plasmons are tuned on- and off-resonance with respect to externally incident light. As a result, a remarkable modulation depth (i.e., the maximum relative variation with/without graphene doping) exceeding 90% in transmission and even more dramatic in reflection (>600%) is predicted for graphene-loaded silver films of 1-5 nm thickness and currently attainable lateral dimensions. These new structures hold great potential for fast low-power electro optical modulation. PMID- 27561790 TI - Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis. AB - KEY POINTS: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known. In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls. Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity. The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 +/- 9, 35 +/- 14, 37 +/- 8 bursts min-1 ) compared to NC (22 +/- 9 bursts min-1 ; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients [5(3-8), 4 (2-7), 6 (4-9) ms mmHg-1 ] compared to NC [11 (8-15) ms mmHg-1 ; P = 0.002]. HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events. PMID- 27561791 TI - Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury. AB - Exogenous Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective in animal models of brain injury, and has been considered as a potential therapeutic. Akt mTOR and MAPK are downstream targets of IGF-1 signaling that are activated after brain injury. However, both brain injury and mTOR are linked to epilepsy, raising the possibility that IGF-1 may be epileptogenic. Here, we considered the role of IGF-1 in development of epilepsy after brain injury, using the organotypic hippocampal culture model of post-traumatic epileptogenesis. We found that IGF-1 was neuroprotective within a few days of injury but that long-term IGF-1 treatment was pro-epileptic. Pro-epileptic effects of IGF-1 were mediated by Akt mTOR signaling. We also found that IGF-1 - mediated increase in epileptic activity led to neurotoxicity. The dualistic nature of effects of IGF-1 treatment demonstrates that anabolic enhancement through IGF-1 activation of mTOR cascade can be beneficial or harmful depending on the stage of the disease. Our findings suggest that epilepsy risk may need to be considered in the design of neuroprotective treatments for brain injury. PMID- 27561793 TI - 1,25(OH)2 D3 improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR-related mechanisms in type 1 diabetes. AB - SCOPE: Diabetic cardiomyopathy is one of the most important cardiac complications associated with diabetes. However, the mechanisms underlying diabetic cardiomyopathy remain unclear. The PARP1, SIRT1, and mTOR pathways have been implicated in cardiac diseases, and they are also associated with diabetes. 1,25(OH)2 D3 was recently recognized as a potential PARP1inhibitor in a macrophage cell line. The aim of our study was to investigate whether 1,25(OH)2 D3 can improve diabetic cardiomyopathy through a vitamin D receptor (VDR) dependent mechanism associated with the PARP1/SIRT1/mTOR pathway. METHODS AND RESULTS: 1,25(OH)2 D3 -treated diabetic rats displayed improved left ventricular wall thickness and end-diastolic/systolic diameter, end-diastolic/systolic volume, left ventricular ejection fraction, fractional shortening, atrial natriuretic peptide, and brain natriuretic peptide gene expression, and interstitial fibrosis compared with untreated diabetic rats, while silencing the VDR gene in DM rats blocked the above results. 1,25(OH)2 D3 treatment also decreased PARP1 and increased SIRT1 expression levels and repressed the phosphorylation of mTOR. Treating neonatal cardiomyocytes with 1,25(OH)2 D3 and a PARP1 inhibitor decreased PARP1 and increased SIRT1 protein expression. CONCLUSION: The present study demonstrates that 1,25(OH)2 D3 treatment has the potential to improve diabetic cardiomyopathy in rats and suggests that VD-VDR signaling induces this protective effect against diabetic cardiomyopathy might partly through the PARP1/SIRT1/mTOR pathway. PMID- 27561792 TI - A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity. AB - Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength. PMID- 27561794 TI - Mortality among tuberculosis patients under DOTS programme: a historical cohort study. AB - BACKGROUND: In high human immunodeficiency virus (HIV) prevalence population, tuberculosis (TB) is the leading cause of morbidity and mortality. HIV is driving the TB epidemic in many countries, especially those in sub-Saharan Africa. We assessed the survival time and predictors of mortality among tuberculosis patients under directly observed treatment, short course (DOTS) strategy in Dessie Referral Hospital tuberculosis clinic, Northeast Ethiopia. METHOD: A historical cohort design was utilized to assess survival time and determinants of mortality. A total of 1260 records of patients who started ant-tuberculosis treatment from January 2006 up to December 2010 were analyzed. Survival curves were estimated using Kaplan-Meier and were compared using the Log-rank test. The Cox proportional hazard model was used to assess the relationship between baseline variables and mortality. RESULTS: Out of the 1260 registered patients, 117 (9.3 %) died over the entire follow-up period. Among those died, 113 (18 %) were HIV positive and 4 (0.6 %) were HIV negative. The 1260 patients contributed a cumulative total of 634.25 person-years observation. CONCLUSION: The mortality of HIV positive tuberculosis patients was higher than those of HIV negative patients and the use of cotrimoxazole preventive therapy increased the survival time of patients. PMID- 27561796 TI - [Editorial: Lung Cancer with Brain Metastasis]. PMID- 27561795 TI - Room-temperature tetragonal non-collinear Heusler antiferromagnet Pt2MnGa. AB - Antiferromagnetic spintronics is a rapidly growing field, which actively introduces new principles of magnetic storage. Despite that, most applications have been suggested for collinear antiferromagnets. In this study, we consider an alternative mechanism based on long-range helical order, which allows for direct manipulation of the helicity vector. As the helicity of long-range homogeneous spirals is typically fixed by the Dzyaloshinskii-Moriya interactions, bi-stable spirals (left- and right-handed) are rare. Here, we report a non-collinear room temperature antiferromagnet in the tetragonal Heusler group. Neutron diffraction reveals a long-period helix propagating along its tetragonal axis. Ab-initio analysis suggests its pure exchange origin and explains its helical character resulting from a large basal plane magnetocrystalline anisotropy. The actual energy barrier between the left- and right-handed spirals is relatively small and might be easily overcome by magnetic pulse, suggesting Pt2MnGa as a potential candidate for non-volatile magnetic memory. PMID- 27561797 TI - [Research Progress of EGFR-TKI Therapy for Patients with Central Nervous System ?Metastases from Non-small Cell Lung Cancer]. AB - Approximately half of all patients with non-small cell lung cancer (NSCLC) develop central nervous system metastases during the course of their disease which indicate poor prognosis. A part of NSCLC patients demonstrates activating epidermal growth factor receptor gene (EGFR) mutations who represent effectiveness and well tolerance of EGFR-specific tyrosine kinase inhibitors (TKIs) therapy. Although the systemic efficacy of targeted agents is established, the efficacy of central nervous system (CNS) metastases is not as well characterized. In this article, we review recent data on the use of EGFR inhibitors for treatment of patients with NSCLC and CNS metastases. PMID- 27561798 TI - [Timing of Whole Brain Radiotherapy on Survival of Patients with EGFR-mutated ?Non-small Cell Lung Cancer and Brain Metastases]. AB - BACKGROUND: There is no high-level evidence for the time of whole brain radiotherapy (WBRT) for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) and brain metastases. The aim of this study is to assess the appropriate timing of WBRT for patients with EGFR-mutated NSCLC and brain metastases (BM). METHODS: There were 78 patients diagnosed with EGFR-mutated NSCLC and BM in Beijing Chest Hospital between August 2009 and May 2015. 48 untreated patients who received both WBRT and EGFR-tyrosine kinase inhibitors (TKIs) therapy. Prognostic factors of intracranial progression-free survival (PFS) and overall survival (OS) were identified by Cox proportional hazards modeling. RESULTS: Intracranial objective response rate was 81.3% and disease control rate was 93.8%. Median intracranial PFS was 10 months. Median OS was 18 months. Multivariate analysis of intracranial PFS revealed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (HR=30.436, 95%CI: 4.721-196.211, P<0.001) and early WBRT (HR=3.663, 95%CI: 1.657-8.098, P=0.001) had a better intracranial PFS. Multivariate analysis of OS revealed that PS 0-1 (HR=57.607, 95%CI: 6.135-540.953, P<0.001), early WBRT (HR=2.757, 95%CI: 1.140 6.669, P=0.024), and stereotactic radiosurgery (HR=5.964, 95%CI: 1.895-18.767, P=0.002) were independent prognostic factors of OS. CONCLUSIONS: Early WBRT combined with EGFR-TKIs can improve outcomes of patients with EGFR-mutated NSCLC and BM, but it needs to be confirmed by large-sample-size and multicenter prospective clinical trials. PMID- 27561799 TI - [Timing of Brain Radiation Therapy Impacts Outcomes in Patients with ?Non-small Cell Lung Cancer Who Develop Brain Metastases]. AB - BACKGROUND: Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. METHODS: Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. RESULTS: Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; P<0.01). Receiving tyrosine kinase inhibitor (TKI) therapy after the diagnosis of brain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; P<0.01), whereas receiving TKI as first line therapy did not (17.9 months vs 15.2 months; P=0.289). CONCLUSIONS: Our study suggests that the use of deferred brain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed. PMID- 27561800 TI - [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer ?with Brain Metastases]. AB - Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID- 27561801 TI - [Treatment of Patients with ALK-positive Non-small Cell Lung Cancer ?and Brain Metastases]. AB - BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is an important subtype of lung cancer. The standard modality of ALK positive NSCLC with brain metastases remains uncertain. METHODS: We collected data on clinical characteristics and treatment of patients with ALK-positive NSCLC and brain metastases between March 2013 and March 2016 and retrospectively analyzed patient outcomes. RESULTS: In 84 ALK-positive patients with advanced NSCLC, 22 (26.2%) had brain metastases during the initial diagnosis of lung cancer, among which 3 patients with EGFR mutation were excluded, and 19 patients were analyzed. Median intracranial progression-free survival (PFS) was 12.0 months. PFS for patients who received first-line local brain therapy (P=0.021) and crizotinib therapy (P=0.030) was superior to PFS for patients without such therapies. PFS for patients who received first-line crizotinib combined with local brain therapy was 27.0 months and only 4.2 months for those who received crizotinib alone. CONCLUSIONS: First-line crizotinib therapy combined with local brain treatment can improve intracranial PFS for ALK-positive NSCLC with brain metastases. This finding should be confirmed further through multicenter, prospective clinical trials with large sample size. PMID- 27561802 TI - [Crizotinib Treatment Combined with Resection and Whole-brain Radiation Therapy ?in A ROS1 Rearranged Lung Adenocarcinoma with Brain Metastasis: ?Case Report and Literature Review]. AB - BACKGROUND: Lung cancer with brain metastasis had poor prognosis. Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase) rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier. In the present study, we reported one case of ROS1 fusion lung adenocarcinoma with symptomatic brain matastasis, who was treated with brain metastases resection, crizotinib, and whole brain radiotherapy plus boost to residual brain metastasis. The safety and efficacy was summarized. METHODS: At first, surgical resection was used to relive mass effect and to biopsy. Then crizotinib (250 mg, bid) was chosen for the existence of ROS1 fusion gene. Whole brain radiotherapy plus boost to residual brain metastasis were used after surgery. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST) v1.1 and brain metastasis were evaluated by computer tomography (CT)/magnetic resonance imaging (MRI) image. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE) v4.0. RESULTS: After taking crizotinib for 3 months, the lung lesions were close to complete response (CR), the brain metastasis were partial response (PR), the abdomen metastasis were CR and the symptom of blurred vision relieved. CONCLUSIONS: Crizotinib combined with palliative operation and radiation therapy (WBRT plus boost to residual brain metastasis) in the treatment of ROS1 fusion gene positive lung adenocarcinoma with symptomatic brain metastases, can effectively control intracranial lesions with good tolerance. PMID- 27561803 TI - [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer ?with Brain Metastasis]. AB - Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work. PMID- 27561804 TI - [Analysis of Clinicopathological Feature and Prognosis for ?Leptomeningeal Metastasis in Non-small Cell Lung Cancer]. AB - BACKGROUND: Leptomeningeal metastases (LM) is one of the most serious complications of advanced non-small cell lung cancer (NSCLC) due to the lower quality of life and poor prognosis. The aim of this study is to analyze the clinicopathological features and prognosis of patients with LM from NSCLC (NSCLC LM). METHODS: Clinical data of 3 patients with NSCLC-LM collected from January 2015 to June 2016 were analyzed with a brief review. RESULTS: All 3 patients had adenocarcinoma histology harboring epidermal growth factor receptor (EGFR) exon 21 point mutations (m). Of the 3 cases, 1 was male, 2 were female. The mean age was 61.3 years (range, 59-64 years). The main clinical manifestations and positive physical examination included headache (3/3), dizziness (3/3), nausea (3/3) and vomiting (3/3), epilepsy (2/3), diplopia (1/3), hearing loss (1/3) and meningeal stimulation sign (3/3). The median time from symptom to diagnosis of LM was 2.3 months (range, 1 to 4 months). Except 1 patient with lung cancer and LM diagnosised at the same time, the other 2 cases received the diagnosis of LM after tyrosine kinase inhibitors (TKIs) therapy or chemotherapy respectively, the median time from diagnosis of NSCLC to LC was 8.5 months. The brain enhanced magnetic resonance imaging (MRI) manifestations of all 3 cases revealed linear meningeal enhancement. Cerebrospinal fluid in 3 cases were positive cytology in whom two cases had EGFR exon 21 L858R mutations, consistenting with the lung tissue. The symptom of the 2 cases improved after TKIs therapy, and temozolomide was used as supplement of 1 case of which the progression-free survival (PFS) and overall survival (OS) was 4.9 months and 13.9 months respectively. CONCLUSIONS: Lung adenocarcinoma with sensitive EGFR mutations are likely to appear LM. Lacking of typical symptoms, NSCLC-LM was easily to be missed and misdiagnosed. TKIs therapy combined with temozolomide may be effective therapies for EGFRm NSCLC-LM patients.?. PMID- 27561805 TI - [Clinical Features of Intradural Extramedullary Spinal Cord Metastases ?in Primary Lung Cancer]. AB - BACKGROUND: Intradural extramedullary spinal cord metastases in lung cancer is rare, and it leads to severe neurological damage. The aim of this study is to identify the clinical features of intradural extramedullary spinal cord metastases in primary lung cancer patients. METHODS: The 8 cases of lung cancer with intradural extramedullary metastases, who were hospitalized in Peking Union Medical College Hospital (PUMCH) during May 2013 to May 2016, were enrolled in the retrospective study. Medical charts of the 8 patients were reviewed systematically. RESULTS: Intradural extramedullary spinal cord metastases was diagnosed in 7 cases with non-small cell lung cancer (NSCLC) and 1 case with small cell lung cancer (SCLC). Cauda equina syndrome was the most common clinical manifestation. Malignant cells in cerebrospinal fluid were positive in all the 5 cases (100%) who underwent lumbar puncture. Contrast-enhanced magnetic resonance imaging (MRI) of spine manifested as diffuse abnormal enhancement of pial lining of spinal cordin 3 cases, intradural extramedullary nodules in 4 cases, and both of them in 1 case. Neurological symptoms were improved or stable in 4 cases who underwent targeted therapy and/or radiotherapy. The median overall survival was 5.8 months. CONCLUSIONS: Intradural extramedullary spinal cord metastases can be diagnosed with caution according to its neurological symptoms and contrast enhanced MRI presentation.Targeted therapy and/or radiotherapy may be effective for symptoms control. PMID- 27561806 TI - [Investigation of Gene Expression Profile of A549 Cells after Overexpression of GPC5 ?by High Throughput Transcriptome Sequencing]. AB - BACKGROUND: Glypican-5 (GPC5) is an important tumor suppressor, while little is known about the impact of GPC5 on proliferation ability and gene expression in lung adenocarcinoma cell lines. Here, we stably overexpressed GPC5 in A549 cells and investigated the impact of cell proliferation ability and gene expression. METHODS: A549 cells that stably overexpressed GPC5 were constructed by lentivirus. Cell counter kit 8 (CCK8), colony formation, EdU assay were conducted to analyze cell proliferation ability, and transcriptome sequencing was utilized to investigate gene expression profile. RESULTS: CCK8 assay showed that compared with empty vector, overexpression of GPC5 significantly inhibited cell proliferation rate in A549 cells and the number of colony was also decreased (181+/-17 vs 278+/-23). EdU assay also confirmed the percentage of positive staining cells decreased after GPC5 overexpression. Transcriptome sequencing revealed that 2,108 genes were differentially expressed after GPC5 overexpression. Among these differentially expressed genes, 47 genes of the Gene Ontology item "positive regulation of cell proliferation" were downregulated. CONCLUSIONS: Overexpression of GPC5 inhibited proliferation ability in lung adenocarcinoma A549 cells and genes with the function of "positive regulation of cell proliferation" were downregulated. PMID- 27561807 TI - [Serum CYFRA21-1 is Correlated with the Efficacy of Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor in Non-small Cell Lung Cancer Patients Harboring EGFR Mutations]. AB - BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) are the standard first-line treatment regimen for EGFR mutated non-small cell lung cancer (NSCLC) patients. However, the efficacy of EGFR-TKIs widely varies. The aim of this study is to determine whether the pretreatment serum cytokeratin-19 fragments (CYFRA21-1) and carcinoembryonic antigen (CEA) are associated with the efficacy of EGFR-TKIs in EGFR-mutated NSCLC patients. METHODS: We retrospectively enrolled 194 NSCLC patients harboring EGFR mutations who received EGFR-TKIs. Clinical characteristics were collected, and the relation between the efficacy of EGFR-TKIs and pretreatment serum CYFRA21-1 and CEA was analyzed. RESULTS: In all cases, progression-free survival (PFS) in patients with high CYFRA21-1 level was significantly shorter than PFS in patients with normal CYFRA21-1 (7.0 vs 11.9 months, P<0.001). Overall survival (OS) in patients with high CYFRA21-1 was significantly shorter than in the normal-CYFRA21-1 group (12.6 vs 28.0 months, P<0.001). In adenocarcinoma patients, PFS in the high-CYFRA21-1 level group was significantly shorter than in patients with normal CYFRA21-1 (7.0 vs 12.0 months, P<0.001). OS in patients with high CYFRA21-1 was significantly shorter than that in the normal-CYFRA21-1 group (13.1 vs 28.1 months, P<0.001). Among squamous carcinoma patients, CYFRA21-1 level did not affect survival. No significant difference in PFS and OS was observed between patients with high CEA and patients with normal CEA. CONCLUSIONS: EGFR-mutated patients with high CYFRA21-1 had significantly shorter PFS and OS than patients with normal CYFRA21 1 after receiving EGFR-TKIs. Pretreatment serum CYFR21-1 level was a predictive marker of EGFR-TKI treatment in EGFR-mutated NSCLC patients.?. PMID- 27561808 TI - [Application of Interventional Bronchoscopy in Pulmonary Peripheral Lesions]. AB - Lung cancer is the leading cause of cancer-related mortality worldwide. A low cure rate of lung cancer is not only attributed to intrinsic aggressive biological behavior, but also little attention to lung cancer screening. With lung screening methods continuous progress, peripheral pulmonary lesions detection rate gradually increased. Currently, a transbronchial approach using a bronchoscope or computed tompgraphy (CT) guided transthoracic needle aspiration/biopsy have been the most generally accepted methods for diagnosing peripheral pulmonary lesions. However, conventional bronchoscopy has a poor diagnostic yield and CT-guided approach has high rates of pneumothorax for such peripheral pulmonary lesions. Therefore, clinicians will be challenged with the task of providing the means to provide a safe and minimally invasive method of obtaining accurate tissue diagnostics for the pulmonary peripheral lesions. New bronchoscopic interventional diagnosis technologies have recommended in clinical gradually. They can effectively improve the peripheral pulmonary lesions diagnosis rate, shorten the time of diagnosis, and make the patients get timely and effective treatment. In this paper, we reviewed briefly available technologies to aid clinicians in attempts at minimally invasive techniques. PMID- 27561810 TI - An anatomical variation of the MSAP flap: Single direct cutaneous perforator in the posterior calf region. PMID- 27561813 TI - Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age. AB - With age, somatically derived mitochondrial DNA (mtDNA) deletion mutations arise in many tissues and species. In skeletal muscle, deletion mutations clonally accumulate along the length of individual fibers. At high intrafiber abundances, these mutations disrupt individual cell respiration and are linked to the activation of apoptosis, intrafiber atrophy, breakage, and necrosis, contributing to fiber loss. This sequence of molecular and cellular events suggests a putative mechanism for the permanent loss of muscle fibers with age. To test whether mtDNA deletion mutation accumulation is a significant contributor to the fiber loss observed in aging muscle, we pharmacologically induced deletion mutation accumulation. We observed a 1200% increase in mtDNA deletion mutation-containing electron transport chain-deficient muscle fibers, an 18% decrease in muscle fiber number and 22% worsening of muscle mass loss. These data affirm the hypothesized role for mtDNA deletion mutation in the etiology of muscle fiber loss at old age. PMID- 27561811 TI - Turmeric extract and its active compound, curcumin, protect against chronic CCl4 induced liver damage by enhancing antioxidation. AB - BACKGROUND: Curcumin, a major active component of turmeric, has previously been reported to alleviate liver damage. Here, we investigated the mechanism by which turmeric and curcumin protect the liver against carbon tetrachloride (CCl4) induced injury in rats. We hypothesized that turmeric extract and curcumin protect the liver from CCl4-induced liver injury by reducing oxidative stress, inhibiting lipid peroxidation, and increasing glutathione peroxidase activation. METHODS: Chronic hepatic stress was induced by a single intraperitoneal injection of CCl4 (0.1 ml/kg body weight) into rats. Turmeric extracts and curcumin were administered once a day for 4 weeks at three dose levels (100, 200, and 300 mg/kg/day). We performed ALT and AST also measured of total lipid, triglyceride, cholesterol levels, and lipid peroxidation. RESULT: We found that turmeric extract and curcumin significantly protect against liver injury by decreasing the activities of serum aspartate aminotransferase and alanine aminotransferase and by improving the hepatic glutathione content, leading to a reduced level of lipid peroxidase. CONCLUSIONS: Our data suggest that turmeric extract and curcumin protect the liver from chronic CCl4-induced injury in rats by suppressing hepatic oxidative stress. Therefore, turmeric extract and curcumin are potential therapeutic antioxidant agents for the treatment of hepatic disease. PMID- 27561814 TI - Folic Acid and Grape Seed Extract Prevent Azathioprine-induced Fetal Malformations and Renal Toxicity in Rats. AB - Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co-administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA-induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA-induced oxidative renal damages. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27561809 TI - A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study. AB - Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions. PMID- 27561815 TI - Pubertal Expression of alpha4betadelta GABAA Receptors Reduces Seizure-Like Discharges in CA1 Hippocampus. AB - More than half of children with epilepsy outgrow their seizures, yet the underlying mechanism is unknown. GABAergic inhibition increases at puberty in female mice due to expression of extrasynaptic alpha4betadelta GABAA receptors (GABARs). Therefore, we tested the role of these receptors in regulating seizure like discharges in CA1 hippocampus using a high K(+) (8.5 mM) seizure model. Spontaneous field potentials were recorded from hippocampus of pre-pubertal (~28 32 PND) and pubertal (~35-44 PND) female wild-type or alpha4-/- mice. The coastline length, a measure of burst intensity, was assessed. 8.5 mM K(+) induced seizure-like discharges in over 60% of pre-pubertal slices, but only in 7% of pubertal slices, where the coastline length was reduced by 70% (P = 0.04). However, the pubertal decrease in seizure-like discharges was not seen in the alpha4-/-, implicating alpha4betadelta GABARs as the cause of the decreased seizure-like activity during puberty. Administration of THIP or DS2, to selectively increase alpha4betadelta current, reduced activity in 8.5 mM K(+) at puberty, while blockade of alpha5-GABARs had no effect. GABAergic current was depolarizing but inhibitory in 8.5 mM K(+), suggesting a mechanism for the effects of alpha4betadelta and alpha5-GABARs, which exhibit different polarity dependent desensitization. These data suggest that alpha4betadelta GABARs are anti-convulsant during adolescence. PMID- 27561817 TI - A genome-wide loss-of-function screening method for minimizing false-negatives caused by functional redundancy. PMID- 27561816 TI - Structural basis of prokaryotic NAD-RNA decapping by NudC. PMID- 27561818 TI - The 17th Acute Disease Quality Initiative International Consensus Conference: Introducing Precision Renal Replacement Therapy. PMID- 27561819 TI - Shared Decision Making to Improve the Emergency Care of Older Adults: A Research Agenda. AB - Older emergency department patients have high rates of serious illness and injury, are at high risk for side effects and adverse events from treatments and diagnostic tests, and in many cases, have nuanced goals of care in which pursuing the most aggressive approach is not desired. Although some forms of shared decision making (SDM) are commonly practiced by emergency physicians caring for older adults, broader use of SDM in this setting is limited by a lack of knowledge of the types of patients and conditions for which SDM is most helpful and the approaches and tools that can best facilitate this process. We describe a research agenda to generate new knowledge to optimize the use of SDM during the emergency care of older adults. PMID- 27561820 TI - Some breast cancer patients with low genetic risk may not need chemotherapy, trial shows. PMID- 27561821 TI - Hyponatremia with Persistent Elevated Urinary Fractional Uric Acid Excretion: Evidence for Proximal Tubular Injury? AB - BACKGROUND/AIMS: Hyponatremia associated with high urinary fractional excretion of uric acid which persists after serum sodium is corrected is the cardinal feature of salt losing nephropathy (SLN). We hypothesize that low grade proximal tubular injury is present in SLN because the proximal tubule is the main site of uric acid and sodium transport. METHODS: Five subjects with SLN were compared to four subjects with recurrent hyponatremia and three healthy individuals. Urinary NGAL (neutrophil gelatinase associated lipocalin, a marker of tubular injury) and fasting urinary fructose levels (a marker of proximal tubular injury) were measured. RESULTS: Subjects with SLN (n=5) showed elevated fractional uric acid excretion (22 +/- 6 vs 4 +/- 2 percent, p<0.0001), elevated urinary NGAL levels (62 +/- 37 vs 9 +/- 7 ng/mg creatinine, p=0.001) and fasting urinary fructose levels compared with the 7 controls (383 +/- 465 vs 60 +/- 34umole/ug creatinine, p <0.001). A strong correlation between urinary NGAL levels and urinary fructose levels was observed (r =0.87, p<0.001). CONCLUSION: High urinary fractional excretion of uric acid in SLN is associated with elevated NGAL and fasting urinary fructose levels suggesting that SLN may involve tubular injury. PMID- 27561822 TI - Comparison of active treatments for impaired glucose regulation: a Salford Royal Foundation Trust and Hitachi collaboration (CATFISH): study protocol for a randomized controlled trial. AB - BACKGROUND: Diabetes is highly prevalent and contributes to significant morbidity and mortality worldwide. Behaviour change interventions that target health and lifestyle factors associated with the onset of diabetes can delay progression to diabetes, but many approaches rely on intensive one-to-one contact by specialists. Health coaching is an approach based on motivational interviewing that can potentially deliver behaviour change interventions by non-specialists at a larger scale. This trial protocol describes a randomized controlled trial (CATFISH) that tests whether a web-enhanced telephone health coaching intervention (IGR3) is more acceptable and efficient than a telephone-only health coaching intervention (IGR2) for people with prediabetes (impaired glucose regulation). METHODS: CATFISH is a two-parallel group, single-centre individually randomized controlled trial. Eligible participants are patients aged >=18 years with impaired glucose regulation (HbA1c concentration between 42 and 47 mmol/mol), have access to a telephone and home internet and have been referred to an existing telephone health coaching service at Salford Royal NHS Foundation Trust, Salford, UK. Participants who give written informed consent will be randomized remotely (via a clinical trials unit) to either the existing pathway (IGR2) or the new web-enhanced pathway (IGR3) for 9 months. The primary outcome measure is patient acceptability at 9 months, determined using the Client Satisfaction Questionnaire. Secondary outcome measures at 9 months are: cost of delivery of IGR2 and IGR3, mental health, quality of life, patient activation, self-management, weight (kg), HbA1c concentration, and body mass index. All outcome measures will be analyzed on an intention-to-treat basis. A qualitative process evaluation will explore the experiences of participants and providers with a focus on understanding usability of interventions, mechanisms of behaviour change, and impact of context on delivery and user acceptability. Qualitative data will be analyzed using Framework. DISCUSSION: The CATFISH trial will provide a pragmatic assessment of whether a web-based information technology platform can enhance acceptability of a telephone health coaching intervention for people with prediabetes. The data will prove critical in understanding the role of web applications to improve engagement with evidence-based approaches to preventing diabetes. TRIAL REGISTRATION: ISRCTN16534814 . Registered on 7 February 2016. PMID- 27561824 TI - [Academic carriers in oncology and radiotherapy: Explanations for the readers of Bulletin du Cancer]. PMID- 27561823 TI - Randomized clinical trial comparing surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy for the treatment of great saphenous varicose veins. AB - BACKGROUND: Endovenous ablation techniques and ultrasound-guided foam sclerotherapy (UGFS) have largely replaced open surgery for treatment of great saphenous varicose veins. This was a randomized trial to compare the effect of surgery, endovenous laser ablation (EVLA) (with phlebectomies) and UGFS on quality of life and the occlusion rate of the great saphenous vein (GSV) 12 months after surgery. METHODS: Patients with symptomatic, uncomplicated varicose veins (CEAP class C2-C4) were examined at baseline, 1 month and 1 year. Before discharge and at 1 week, patients reported a pain score on a visual analogue scale. Preoperative and 1-year assessments included duplex ultrasound imaging and the Aberdeen Varicose Vein Severity Score (AVVSS). RESULTS: The study included 214 patients: 65 had surgery, 73 had EVLA and 76 had UGFS. At 1 year, the GSV was occluded or absent in 59 (97 per cent) of 61 patients after surgery, 71 (97 per cent) of 73 after EVLA and 37 (51 per cent) of 72 after UGFS (P < 0.001). The AVVSS improved significantly in comparison with preoperative values in all groups, with no significant differences between them. Perioperative pain was significantly reduced and sick leave shorter after UGFS (mean 1 day) than after EVLA (8 days) and surgery (12 days). CONCLUSION: In comparison with open surgery and EVLA, UGFS resulted in equivalent improvement in quality of life but significantly higher residual GSV reflux at 12-month follow-up. PMID- 27561825 TI - Testing the cultural group selection hypothesis in Northern Ghana and Oaxaca. AB - We examine the cultural group selection (CGS) hypothesis in light of our fieldwork in Northern Ghana and Oaxaca, highly multi-ethnic regions. Our evidence fails to corroborate two central predictions of the hypothesis: that the cultural group is the unit of evolution, and that cultural homogenization is to be expected as the outcome of a selective process. PMID- 27561828 TI - Knockdown of Myosin 6 inhibits proliferation of oral squamous cell carcinoma cells. AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts for 95% of all oral cancer with higher mortality and morbidity rates worldwide. However, the potential molecular mechanism of OSCC remains largely unclear. Myosin VI (MYO6) is a unique actin motor and reported to be overexpressed in several cancers. This study aims to examine the functional relationship between OSCC and MYO6. METHODS: The mRNA expression of MYO6 was firstly investigated by analyzing data derived from Oncomine database. On the basis of the results, the expression of MYO6 was knocked down using lentivirus-delivered RNA interference in human OSCC cell line CAL27, as confirmed by qPCR and Western blot analysis. Stable MYO6 knockdown cells were employed to determine the effects of MYO6-silencing on cell growth by MTT, colony formation and cell cycle distribution and apoptosis by flow cytometry assay. Moreover, the expressions of cell apoptotic proteins were examined by Western blot analysis. RESULTS: We first observed MYO6 was overexpressed in tongue squamous cell carcinoma TSCC belongs to OSCC, compared with normal tissues. For cellular analysis, shRNA sequences against MYO6 could efficiently reduce its expression in CAL27 cells. Knockdown of MYO6 significantly decreased cell proliferation, caused cell cycle arrest at G2/M phase, and promoted cell apoptosis. Moreover, cell apoptosis-associated proteins, caspase-3 and PARP, were obviously upregulated in CAL27 after MYO6-silencing. CONCLUSION: MYO6 could play an essential role in the growth of OSCC cells via regulation of cell cycle progression and apoptosis. PMID- 27561827 TI - Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study. AB - BACKGROUND: Type 1 diabetes is associated with increased cardiovascular disease (CVD). Decreased endothelial progenitor cells (EPCs) number plays a pivotal role in reduced endothelial repair and development of CVD. We aimed to determine if cardioprotective effect of metformin is mediated by increasing circulating endothelial progenitor cells (cEPCs), pro-angiogenic cells (PACs) and decreasing circulating endothelial cells (cECs) count whilst maintaining unchanged glycemic control. METHODS: This study was an open label and parallel standard treatment study. Twenty-three type 1 diabetes patients without overt CVD were treated with metformin for 8 weeks (treatment group-TG). They were matched with nine type 1 diabetes patients on standard treatment (SG) and 23 age- and sex-matched healthy volunteers (HC). Insulin dose was adjusted to keep unchanged glycaemic control. cEPCs and cECs counts were determined by flow cytometry using surface markers CD45(dim)CD34(+)VEGFR-2(+) and CD45(dim)CD133(-)CD34(+)CD144(+) respectively. Peripheral blood mononuclear cells were cultured to assess changes in PACs number, function and colony forming units (CFU-Hill's colonies). RESULTS: At baseline TG had lower cEPCs, PACs, CFU-Hills' colonies and PACs adhesion versus HC (p < 0.001-all variables) and higher cECs versus HC (p = 0.03). Metformin improved cEPCs, PACs, CFU-Hill's colonies number, cECs and PACs adhesion (p < 0.05-all variables) to levels seen in HC whilst HbA1c (one-way ANOVA p = 0.78) and glucose variability (average glucose, blood glucose standard deviation, mean amplitude of glycaemic excursion, continuous overall net glycaemic action and area under curve) remained unchanged. No changes were seen in any variables in SG. There was an inverse correlation between CFU-Hill's colonies with cECs. CONCLUSIONS: Metformin has potential cardio-protective effect through improving cEPCs, CFU-Hill's colonies, cECs, PACs count and function independently of hypoglycaemic effect. This finding needs to be confirmed by long term cardiovascular outcome studies in type 1 diabetes. Trial registration ISRCTN26092132. PMID- 27561826 TI - The gastrointestinal tract - a central organ of cannabinoid signaling in health and disease. AB - BACKGROUND: In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract. Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors. After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity. In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARalpha) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer. PURPOSE: The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer. PMID- 27561829 TI - Body ownership and a new proprioceptive role for muscle spindles. AB - Knowledge of which body parts belong to us is referred to as the sense of body ownership. There is increasing evidence that this important aspect of human proprioception is highly malleable. Research into ownership of individual body parts was stimulated by Botvinick and Cohen's rubber-hand illusion (Nature 391,1998, 756), which demonstrated that an artificial body part can be incorporated in one's body representation and can cause real body parts to be sensed erroneously. Here, we review key studies that have advanced our understanding of the sense of body ownership, including the important role played by multisensory integration and spatiotemporal congruence of sensory signals. We also discuss our recent discovery that body ownership can be induced in response to movement stimuli by signals from a single class of sensory receptor, namely muscle spindles. PMID- 27561830 TI - Ultrasociality and the sexual divisions of labor. AB - The ultrasociality thesis proposes that the same "mechanistic evolutionary forces" may be at work in the evolution of insect eusociality and human ultrasociality in relation to agriculture. Wide variation in the reproductive division of labor among differing highly social phyla points to a resemblance of outcomes arising from very different selective environments and possibly different forces. PMID- 27561832 TI - Radiation Dose Reduction in 4D Cerebral CT Angiography by Individualized Estimation of Cerebral Circulation Time. AB - BACKGROUND AND PURPOSE: The novel technique of 4D CTA for dynamic assessment of the intracranial vessels has a greater radiation burden than conventional CTA. Previous descriptions of the technique used a fixed-duration exposure protocol. This study examines the potential for dose reduction by individualizing exposure time to patient physiology by the use of time-enhancement curve techniques as previously applied in CT angiography and venography. MATERIALS AND METHODS: 4D CTA examinations performed at our institution were retrospectively reviewed. Scan protocols used a test-bolus scan with either a subjective estimate of the main acquisition timing (estimated-duration method) or a quantitative measure (measured-duration method). The estimated-duration method used peak arterial enhancement to determine the start of exposure, with the duration chosen at the radiologist's discretion. The measured-duration method used arterial and venous time-enhancement curves to determine exposure start and duration. Exposure duration, study adequacy, quality score, and maximum venous enhancement were compared among groups. RESULTS: One hundred fifty-one examinations used the estimated-duration method, and 53 used measured-duration. The measured-duration method used a shorter exposure time (10 versus 15.8 seconds; P < .001). There was no statistically significant difference in the study adequacy rate, subjective quality score, or maximum venous enhancement. The radiation dose was reduced by 51% in the measured-duration method (3021 mGy * cm, 6.9 mSv, versus 1473 mGy * cm, 3.4 mSv). Both methods showed good agreement with DSA (kappa = 0.88 for estimated-duration, kappa = 1.0 for measured duration). CONCLUSIONS: Exposure time in 4D-CTA can be reduced with dual time-enhancement curves to match exposure to physiology without degrading study adequacy or quality. PMID- 27561831 TI - Improving the Grading Accuracy of Astrocytic Neoplasms Noninvasively by Combining Timing Information with Cerebral Blood Flow: A Multi-TI Arterial Spin-Labeling MR Imaging Study. AB - BACKGROUND AND PURPOSE: Systematic and accurate glioma grading has clinical significance. We present the utility of multi-TI arterial spin-labeling imaging and provide the bolus arrival time maps for grading astrocytomas. MATERIALS AND METHODS: Forty-three patients with astrocytomas (21 men; mean age, 51 years) were recruited. The classification abilities of conventional MR imaging features, normalized CBF value derived from multi-TI arterial spin-labeling imaging, normalized bolus arrival time, and normalized CBF derived from single-TI arterial spin-labeling were compared in patients with World Health Organization (WHO) grade II, III, and IV astrocytomas. RESULTS: The normalized CBF value derived from multi-TI arterial spin-labeling imaging was higher in patients with higher grade astrocytoma malignancies compared with patients with lower grade astrocytomas, while the normalized bolus arrival time showed the opposite tendency. The normalized CBF value derived from the multi-TI arterial spin labeling imaging showed excellent performance with areas under the receiver operating characteristic curve of 0.813 (WHO II versus III), 0.964 (WHO II versus IV), 0.872 (WHO III versus IV), and 0.883 (low-grade-versus-high-grade gliomas). The normalized CBF value derived from single-TI arterial spin-labeling imaging could statistically differentiate the WHO II and IV groups (area under the receiver operating characteristic curve = 0.826). The normalized bolus arrival time effectively identified the WHO grades II and III with an area under the receiver operating characteristic curve of 0.836. Combining the normalized CBF value derived from multi-TI arterial spin-labeling imaging and normalized bolus arrival time improved the diagnostic accuracy from 65.10% to 72.10% compared with the normalized CBF value derived from multi-TI arterial spin-labeling imaging being applied independently. The combination of multi-TI arterial spin-labeling imaging and conventional MR imaging had the best performance, with a diagnostic accuracy of 81.40%. CONCLUSIONS: Multi-TI arterial spin-labeling imaging can evaluate perfusion dynamics by combining normalized bolus arrival time and normalized CBF values derived from multiple TIs. It is superior to single-TI arterial spin-labeling imaging and conventional MR imaging features when applied independently and can improve the diagnostic accuracy when combined with conventional MR imaging for grading astrocytomas. PMID- 27561833 TI - Spectrum of Third Window Abnormalities: Semicircular Canal Dehiscence and Beyond. AB - Third window abnormalities are defects in the integrity of the bony structure of the inner ear, classically producing sound-/pressure-induced vertigo (Tullio and Hennebert signs) and/or a low-frequency air-bone gap by audiometry. Specific anatomic defects include semicircular canal dehiscence, perilabyrinthine fistula, enlarged vestibular aqueduct, dehiscence of the scala vestibuli side of the cochlea, X-linked stapes gusher, and bone dyscrasias. We discuss these various entities and provide key examples from our institutional teaching file with a discussion of symptomatology, temporal bone CT, audiometry, and vestibular-evoked myogenic potentials. PMID- 27561834 TI - A Simplified Model for Intravoxel Incoherent Motion Perfusion Imaging of the Brain. AB - BACKGROUND AND PURPOSE: Despite a recent resurgence, intravoxel incoherent motion MRI faces practical challenges, including limited SNR and demanding acquisition and postprocessing requirements. A simplified approach using linear fitting of a subset of higher b-values has seen success in other organ systems. We sought to validate this method for evaluation of brain pathology by comparing perfusion measurements using simplified linear fitting to conventional biexponential fitting. MATERIALS AND METHODS: Forty-nine patients with gliomas and 17 with acute strokes underwent 3T MRI, including DWI with 16 b-values (range, 0-900 s/mm2). Conventional intravoxel incoherent motion was performed using nonlinear fitting of the standard biexponential equation. Simplified intravoxel incoherent motion was performed using linear fitting of the log-normalized signal curves for subsets of b-values >200 s/mm2. Comparisons between ROIs (tumors, strokes, contralateral brain) and between models (biexponential and simplified linear) were performed by using 2-way ANOVA. The root mean square error and coefficient of determination (R2) were computed for the simplified model, with biexponential fitting as the reference standard. RESULTS: Perfusion maps using simplified linear fitting were qualitatively similar to conventional biexponential fitting. The perfusion fraction was elevated in high-grade (n = 33) compared to low-grade (n = 16) gliomas and was reduced in strokes compared to the contralateral brain (P < .001 for both main effects). Decreasing the number of b-values used for linear fitting resulted in reduced accuracy (higher root mean square error and lower R2) compared with full biexponential fitting. CONCLUSIONS: Intravoxel incoherent motion perfusion imaging of common brain pathology can be performed by using simplified linear fitting, with preservation of clinically relevant perfusion information. PMID- 27561835 TI - Regarding "Computer-Assisted Detection of Cerebral Aneurysms in MR Angiography in a Routine Image-Reading Environment: Effects on Diagnosis by Radiologists". PMID- 27561836 TI - Counterpoint: Appropriately Ambiguous-The Disc Osteophyte Complex. PMID- 27561837 TI - Point: Don't Call Me a DOC! PMID- 27561838 TI - Reply. PMID- 27561839 TI - Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception. AB - Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1MUg, 3MUg and 5MUg/0.2MUL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail flick test. Pre-treatment of the LC with 1MUg, 3MUg and 5MUg/0.2MUL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception. PMID- 27561840 TI - The New -474(C->T) Substitution Discovered in the HBG2 Promoter of a Sardinian deltabeta-Thalassemia Carrier. AB - During a screening for hemoglobinopathies, we found a carrier of the Sardinian deltabeta-thalassemia condition. The proband's hematology and hemoglobin (Hb) profile agreed with those of the other carriers previously identified during our diagnostic program except for the fetal Hb (HbF) composition, which consisted of both alpha2Agamma2 and alpha2Ggamma2 instead of nearly 100% alpha2Agamma2. In order to explain the unusual gamma-chain ratio, sequencing of the Ggamma promoter was carried out and revealed two nucleotide substitutions in cis: C->T at position -474 and A->G at position -309 from the Cap site. The latter had previously been observed in subjects with raised HbF levels, although it has not yet been evaluated at functional level. We used the luciferase assay to determine whether the two mutations modify the transcriptional activity of the Ggamma promoter. Results indicated that the observed in vivo Ggamma-globin production cannot be translated into increased in vitro promoter function, suggesting that the assessed mutations cannot be considered as functional single nucleotide polymorphisms per se; instead, a more complex regulatory mechanism might be involved. PMID- 27561841 TI - How long is now? The multiple timescales of language processing. AB - Christiansen & Chater (C&C) envision language function as a hierarchical chain of transformations, enabling rapid, continuous processing of input. Their notion of a "Now-or-Never" bottleneck may be elaborated by recognizing that timescales become longer at successive levels of the sensory processing hierarchy - that is, the window of "Now" expands. We propose that a hierarchical "process memory" is intrinsic to language processing. PMID- 27561842 TI - The role of hippocampal insulin signaling on postoperative cognitive dysfunction in an aged rat model of abdominal surgery. AB - AIMS: This study aimed to investigate the role of central insulin signaling, including glycogen synthase kinase 3beta (GSK-3beta), and its therapeutic potential for the prevention of postoperative neurocognitive deficits. MAIN METHODS: In non-insulin experiment, aged rats were divided into a sham group and abdominal surgery group. In insulin experiment, sham and surgically treated rats were distributed into two groups: an intranasal denatured insulin-treated group and intranasal insulin-treated group. Insulin administration started the day of surgery and continued for 3days. Fourteen-days after surgery, cognitive function was assessed using a novel object recognition test, followed by measurement of hippocampal levels of pro-inflammatory cytokines, GSK-3beta, and phosphorylated GSK-3beta (pGSK-3beta(ser9)). Under identical conditions, lipopolysaccharide (LPS)-induced cytokine release from isolated hippocampal microglia was also tested. KEY FINDINGS: In non-insulin experiment, compared with non-surgical animals, the rats that underwent abdominal surgery showed memory deficits and increased hippocampal cytokine levels. The hippocampal ratio of pGSK 3beta(ser9)/GSK-3beta decreased after surgery, a ratio that was positively correlated with novel object recognition performance in the testing phase. Insulin experiment revealed that perioperative intranasal insulin administration could restore the surgery-induced hippocampal neuroinflammation and hyperactivation of GSK-3beta, and prevent impairment in novel object recognition. Furthermore, ex vivo experiments indicated that intranasal insulin administration, as well as pretreatment with SB216763, a GSK-3beta inhibitor, resulted in reduction of the surgery-related microglial hyper-reactivity to LPS. SIGNIFICANCE: Our findings in aged rats suggest that surgical procedures could impair central insulin signaling including GSK-3beta, which makes the individual more susceptible to hippocampal neuroinflammation and related cognitive disorders. PMID- 27561843 TI - Reply to: Impact of laminar air flow on operating room contamination and surgical wound infection rates in clean and contaminated surgery. PMID- 27561844 TI - PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer. AB - PURPOSE: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. METHODS: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end points included safety, pathologic tumour response and overall survival. RESULTS: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64 175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. CONCLUSIONS: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov (NCT00844233). PMID- 27561846 TI - Rapid amelioration of severe manic episodes with right unilateral ultrabrief pulse ECT: a case series of four patients. AB - OBJECTIVE: The aim of this small case series is to describe four cases of severe mania, where ultrabrief pulse electroconvulsive therapy (ECT) was used as a primary mode of treatment. METHODS: A retrospective file review was undertaken of four patients identified as having received ultrabrief pulse ECT for severe mania. The outcome measures for treatment efficacy were the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI). RESULTS: All the patients showed significant clinical improvement. A comparison of pre- and post-treatment YMRS and CGI scores showed a dramatic decrease in all four cases. However, one patient was shifted to brief pulse ECT due to inadequate response. CONCLUSIONS: Ultrabrief pulse ECT may be an effective treatment in cases of severe mania. Due to the very small number of cases in the current case series, no specific conclusions regarding efficacy may be drawn; however, larger, controlled studies would be indicated. PMID- 27561847 TI - Infiltrating bladder cancer: prognostic factors, follow-up and treatment of relapses. AB - CONTEXT: Bladder cancer is the cause of more than 150,000 deaths per year. The overall rate of survival is approximately 45%, with a 10-year recurrence-free rate of 50-59%, with no changes in the last decade. OBJECTIVE: Due to a lack of agreement on the follow-up of cystectomy or on a uniform treatment when faced with the various types of recurrence, we have analysed the most recent literature in an attempt to unify the criteria for the diagnosis and treatment of bladder cancer. ACQUISITION OF EVIDENCE: Review of Spanish and English publications in the medical literature in the last 10 years, highlighting the most significant series in terms of the number of patients, follow-up time, as well as the existing meta-analyses. SYNTHESIS OF THE EVIDENCE: Recurrence after cystectomy can occur in the urinary apparatus (upper urinary tract or distal urethra) and local (cystectomy bed) and/or distant metastases. Despite strict control, more than 60% of the relapses are discovered based on symptoms and not by the routine follow-up test. Locoregional and distant relapses are more common the more advanced the stage at the time of cystectomy, going from 11-21% in pT2N0 to 52 72% when there is lymphocytic N+ involvement. Recurrence in the urethra and/or upper urinary track has other prognostic factors such as multiplicity, the presence of Cis and involvement of prostatic stroma. There are various treatments for tumour relapses. Increasingly, the patient's comorbidity is considered when deciding on the therapeutic strategy. Treatments are typically multimodal and include surgery, radiotherapy and chemotherapy. CONCLUSION: The follow-up of patients who undergo cystectomy should be individualised, taking into account the prognostic factors of recurrence and the patient's comorbidity, assuming that in some cases, multimodal treatment is indicated. PMID- 27561845 TI - The impact of family history on non-medullary thyroid cancer. AB - INTRODUCTION: Around 10% of patients with non-medullary thyroid cancer (NMTC) will have a positive family history for the disease. Although many will be sporadic, families where 3 first-degree relatives are affected can be considered to represent true familial non-medullary thyroid cancer (FNMTC). The genetic basis, impact on clinical and pathological features, and overall effect on prognosis are poorly understood. METHODS: A literature review identified articles which report on genetic, clinical, therapeutic and screening aspects of FNMTC. The results are presented to allow an understanding of the genetic basis and the impact on clinical-pathological features and prognosis in order to inform clinical decision making. RESULTS: The genetic basis of FNMTC is unknown. Despite this, significant progress has been made in identifying potential susceptibility genes. The lack of a test for FNMTC has led to a clinical definition requiring a minimum of 3 first-degree relatives to be diagnosed with NMTC. Although some have shown an association with multi-centric disease, younger age and increased rates of extra-thyroidal extension and nodal metastases, these findings are not supported by all. The impact of FNMTC is unclear with all groups reporting good outcome, and some finding an association with more aggressive disease. The role of screening remains controversial. CONCLUSION: FNMTC is rare but can be diagnosed clinically. Its impact on prognostic factors and the subsequent role in influencing management is debated. For those patients who present with otherwise low-risk differentiated thyroid cancer, FNMTC should be included in risk assessment when discussing therapeutic options. PMID- 27561849 TI - Editorial Comment. PMID- 27561848 TI - Dermatomyositis with anti-TIF-1gamma antibodies as a presenting symptom of underlying triple-negative breast cancer: a case report. AB - BACKGROUND: Dermatomyositis is an autoimmune myopathy characterized by proximal muscle weakness, muscle inflammation, and typical skin findings. It is a rare disease with an incidence of ~1/100 000. About 15-30 % of adult-onset cases are caused by underlying malignancy and dermatomyositis can be the first symptom of undiagnosed cancer, mainly in the case of anti-transcription intermediary factor 1gamma (anti-TIF-1gamma) antibodies presence. TIF-1gamma is a transcriptional cofactor which is implicated in TGFbeta signaling pathway that controls cell proliferation, differentiation, apoptosis, and tumorigenesis. Its expression was shown to be associated with younger age, higher tumor grade, more estrogen receptor negativity, tumors larger than 2 cm, and tendency towards poor outcome in early breast cancer. No association between anti-TIF-1gamma antibodies and prognosis has been proposed yet. CASE PRESENTATION: We report a case of a 43-year old premenopausal woman presenting with the symptoms of systemic rheumatic disease, the most prominent being a typical skin rash and muscle pain. After a series of investigations, the patient was diagnosed with anti-TIF-1gamma positive dermatomyositis and concurrent triple-negative breast cancer (cT1c N3c M0) as an underlying cause. Immediate intravenous corticosteroid therapy relieved the symptoms and enabled anticancer therapy to be commenced. Considering the tumor stage, neoadjuvant therapy with 4 courses of AC (Doxorubicin/Cyclophosphamide) followed by 4 courses of Paclitaxel/Carboplatin was administered. However, no tumor regression was documented and radiotherapy was chosen as the definitive treatment. CONCLUSION: Early detection of anti-TIF-1gamma autoantibodies can contribute to a rapid diagnosis of tumor-associated dermatomyositis and enable immediate anticancer treatment. We demonstrate the emerging role of anti-TIF 1gamma antibodies in the diagnostics of tumor-associated dermatomyositis. Furthermore, we propose a potential role of anti-TIF-1gamma antibodies as a prognostic marker in early breast cancer patients. PMID- 27561850 TI - Editorial Comment. PMID- 27561851 TI - Author Reply. PMID- 27561852 TI - Impact or Impact Factor? PMID- 27561853 TI - Plasma Volume Is Normal but Heterogeneously Distributed, and True Anemia Is Highly Prevalent in Patients With Stable Heart Failure. AB - BACKGROUND: Intravascular volume overload and depletion as well as anemia are associated with increased hospital admissions and mortality in patients with heart failure. This study aimed to accurately measure plasma volume and red cell mass (RCM) in stable patients with chronic heart failure with reduced ejection fraction (HFrEF) and gain more insight into plasma volume regulation and anemia in stable conditions of HFrEF. METHODS AND RESULTS: Plasma volume and RCM measurement based on 99Tc-labeled red blood cells, venous blood sample,s and clinical parameters were obtained in 24 stable HFrEF patients under optimal medical therapy. Measured plasma volume values were compared with predicted values based on body surface area. Plasma volume was on average normal (99.98% of predicted) but heterogeneously distributed (variations of 81%-133%). Neurohumoral activation and medication use were not associated with plasma volume status. Furthermore, anemia based on actual measurement of RCM was present in up to 75% of subjects, but rarely hemodilutional. CONCLUSIONS: In stable chronic HFrEF patients under optimal medical therapy, plasma volume is overall normal but heterogeneously distributed. Anticipated factors such as neurohumoral activation and heart failure medication were not associated with plasma volume. Furthermore, anemia is more common than as assessed by hemoglobin. PMID- 27561855 TI - Addiction Classics. PMID- 27561854 TI - Red LED photobiomodulation reduces pain hypersensitivity and improves sensorimotor function following mild T10 hemicontusion spinal cord injury. AB - BACKGROUND: The development of hypersensitivity following spinal cord injury can result in incurable persistent neuropathic pain. Our objective was to examine the effect of red light therapy on the development of hypersensitivity and sensorimotor function, as well as on microglia/macrophage subpopulations following spinal cord injury. METHODS: Wistar rats were treated (or sham treated) daily for 30 min with an LED red (670 nm) light source (35 mW/cm(2)), transcutaneously applied to the dorsal surface, following a mild T10 hemicontusion injury (or sham injury). The development of hypersensitivity was assessed and sensorimotor function established using locomotor recovery and electrophysiology of dorsal column pathways. Immunohistochemistry and TUNEL were performed to examine cellular changes in the spinal cord. RESULTS: We demonstrate that red light penetrates through the entire rat spinal cord and significantly reduces signs of hypersensitivity following a mild T10 hemicontusion spinal cord injury. This is accompanied with improved dorsal column pathway functional integrity and locomotor recovery. The functional improvements were preceded by a significant reduction of dying (TUNEL(+)) cells and activated microglia/macrophages (ED1(+)) in the spinal cord. The remaining activated microglia/macrophages were predominantly of the anti-inflammatory/wound-healing subpopulation (Arginase1(+)ED1(+)) which were expressed early, and up to sevenfold greater than that found in sham-treated animals. CONCLUSIONS: These findings demonstrate that a simple yet inexpensive treatment regime of red light reduces the development of hypersensitivity along with sensorimotor improvements following spinal cord injury and may therefore offer new hope for a currently treatment-resistant pain condition. PMID- 27561857 TI - Healthy Weight Knowledge and Body Size Disparities in Chinese Adults. AB - OBJECTIVES: This study was an exploration of whether raising the level of knowledge regarding healthy eating and physical activity at all socioeconomic status (SES) levels is vital to reducing the SES gradient in body size disparities. METHODS: This study uses longitudinal data with a total of 20,757 person-years drawn from 11,469 households of individuals aged 18-55 who participated in the 2004, 2006, 2009, and 2011 China Health and Nutrition Survey. Linear mixed-effects regression models capture the link among SES, knowledge of healthy eating and physical activity, and body mass index (BMI). All analyses are stratified by sex. RESULTS: The results show there are knowledge gaps among SES groups from 2004-2011 for both men and women. In addition, there is a positive association between knowledge and BMI for men and no association for women. Conversely, the results suggest differentiated effects of knowledge on women's BMI by educational attainment. CONCLUSIONS: Current intervention programs that focus on raising knowledge regarding what contributes to a healthy weight are limited to reducing body size disparities; understanding social and gender meanings of ideal body size may be the key to curbing the trend toward obesity disparities in China. PMID- 27561856 TI - Intracranial Rosai-Dorfman disease. AB - Rosai-Dorfman disease (RDD) is a rare histioproliferative disorder that only occasionally involves the central nervous system. We present the diagnosis and treatment of five patients with intracranial RDD. The patients were preoperatively misdiagnosed as meningioma or eosinophilic granuloma. All five patients were treated by total or subtotal surgical resection and none of them experienced recurrence. Histopathological examination showed a characteristic emperipolesis, the lymphocytes were engulfed in the S-100 protein and CD68 positive histiocytes, with negative expression of CD1a. Preoperative diagnosis of intracranial RDD is still challenging because the lesion is usually a dural-based lesion that mimics a meningioma. Surgical resection is an effective treatment and radiotherapy, steroid and chemotherapy has not demonstrated reliable therapeutic efficiency. PMID- 27561858 TI - Situational Pressures that Influence Firefighters' Decision Making about Personal Protective Equipment: A Qualitative Analysis. AB - OBJECTIVES: Firefighters are exposed to hazardous conditions as a result of their occupation and often understand the dangers of these toxic exposures; yet, it remains unclear why some refrain from wearing personal protective equipment (PPE) in dangerous situations. We were intrigued by the gap between demonstrated safety knowledge and lack of connection to observed or self-reported safety behaviors, an issue about which there is limited consensus among scholars. METHODS: In a national study of fire service safety climate, 123 firefighters across 12 fire departments participated in 62 interviews and 10 focus groups. RESULTS: Firefighter identity, goal seduction, and situation aversion were the strongest factors of PPE non-compliance, whereas PPE empowerment and individual will promoted PPE use within a fire department. CONCLUSIONS: Understanding situations where PPE use is both practiced and neglected is imperative to improving fire service safety culture. Peer-pressure and leading by example at the peer and organizational levels appear to be essential considerations firefighters undertake when choosing whether or not to engage in safety behavior. PMID- 27561859 TI - Changes in School Health Program Improve Middle School Students' Behaviors. AB - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of environmental activities in a school-based health program among 6th grade students (N = 2315). METHODS: Students enrolled in Project Healthy Schools, a school-based health program designed to reduce childhood obesity and improve cardiovascular health, completed a health questionnaire on recent lifestyle choices including diet, physical activity, and sedentary behaviors. Baseline and follow-up data were compared between students who received educational lessons and students who received educational lessons and additional activities in the schools' environment. We calculated descriptive and one-way ANOVA statistics. RESULTS: Students at schools with educational lessons and environmental activities reported more fruit intake (p = .046), fewer sugary beverages (p = .054) and servings of fatty/sugary foods (p = .002), and more moderate physical activity (p = .009) compared to students with educational lessons only. No beneficial effect was observed in decreasing TV viewing time. Mobile device time increased in both groups. CONCLUSIONS: The present study suggests school-based health programs combining educational lessons and additional environmental activities may improve diet and physical activity in middle school children to a greater degree than educational lessons alone. PMID- 27561860 TI - Primary Care Physicians' Characteristics and Attitudes on Smoking Cessation. AB - OBJECTIVES: Primary care physicians are uniquely positioned to initiate and promote smoking cessation. However, their attitude towards smoking cessation is influenced by many factors, including their own smoking habits and knowledge. The aim of the study was to assess the impact of smoking habits, knowledge, and personal characteristics of primary care physicians on their attitude towards smoking cessation in comparison to a previous study conducted a decade ago. METHODS: Overall, 302 primary care physicians filled out a questionnaire designed specifically to evaluate knowledge, smoking habits, and smoking cessation interventions they use. RESULTS: More never-smoking physicians initiate conversations about smoking cessation, recommend smoking cessation groups, and set quit date to their smoking patients. They also invest greater efforts in patients with smoking complications. More current-smoking physicians advise Nicotine Replacement Therapy and joining Internet forums and telephone consultations. Keeping good relations with the patients plays an important role in the willingness of physicians to initiate a talk. A large proportion of physicians state they would prescribe smoking cessation medications to patients even when contraindicated. CONCLUSION: The various approaches of primary care physicians emphasize the importance of physician education according to their own smoking habits. PMID- 27561861 TI - Nut Intake among Overweight and Obese African-American Women in the Rural South. AB - OBJECTIVE: Nut consumption decreases risk for obesity and chronic diseases, which are prevalent among African-American women in the rural southeastern United States. The quantity and quality of nut intake in this population is unclear. We examined the amount, source, and quality of nut consumption among overweight and obese African-American women in rural Alabama and Mississippi. METHODS: Two 24 hour dietary recalls were administered to 426 women. Mann-Whitney tests, t-tests, and linear regression models identified differences in added sugar and sodium intake between nut consumers and non-consumers, differences in mean nut, added sugar, and sodium intake between stand-alone and incorporated nut sources, and a relationship between nut intake and added sugar and sodium intake. RESULTS: Forty two percent of participants consumed nuts, and 16% met federal recommendations for nut intake. Nut consumption was mainly from incorporated sources (65%), which were higher in added sugar (p < .001) and sodium (p < .001), and lower in nut quantity (p < .001) than stand-alone sources. Nut consumers consumed more daily added sugar (p = .004) and sodium (p = .04) than non-consumers. CONCLUSION: Suboptimal quantity and quality of nut intake may impede the health benefits of nut consumption among African-American women in the rural South. PMID- 27561862 TI - Problematic Use of Video Games and Substance Abuse in Early Adolescence: A Cross sectional Study. AB - OBJECTIVES: Problematic use of video games (PUVG) is associated with substance use in middle school students. The aim of our study was to examine the association between PUVG and substance abuse in children and young adolescents. METHODS: A survey was conducted during the 2014-2015 school year in Padua (northeastern Italy). The sample consisted of 1156 students in grades 6 to 8. A multivariate logistic regression model was applied to seek associations between PUVG (dependent variable) and independent variables. RESULTS: Logistic regression showed that lifetime drunkenness, combined energy drink and alcohol consumption (lifetime), reading comics, and disrespect for rules increased the odds of PUVG, whereas playing competitive sport, eating fruit and/or vegetables daily, finding it easy to talk with fathers and being female lowered the odds of PUVG in early adolescence. CONCLUSIONS: Our findings show that PUVG is more likely in young adolescents at risk of substance abuse. Prevention schemes focusing on early adolescence should be based on a multicomponent intervention strategy that takes PUVG into account. PMID- 27561863 TI - Influences of Sex and BMI on the Weight Level Perception of Others. AB - OBJECTIVES: This study examines how the sex and body mass index (BMI) of both the observer (the interviewer) and the observed (the respondent) influence the way we perceive the weight level of others. METHODS: The study uses mixed-process IV regression and representative data from the Danish Longitudinal Survey of Youth - Children (DLSY-C) with 3015 respondents and 88 interviewers. Face-to-face interviews constitute the social setting, with interviewers estimating the weight level of the respondents, thereby avoiding bias from endogenous sorting of individuals into social contexts. The data include both male and female interviewers and respondents. RESULTS: Women are placed in higher weight categories than men, net of actual BMI. Men tend to underestimate the weight level of women more often than do women. The higher the BMI of the interviewer, the more likely the interviewer is to perceive respondents as belonging to a low weight level category. CONCLUSIONS: The findings underscore the role of own sex and own BMI when estimating the weight level of others, thereby broadening the perspective of weight perception to go beyond individual self-perception to instead capture a general view upon weight levels with possible implications for weight management. PMID- 27561864 TI - Weight Perception and Weight-control Intention among Youth in the COMPASS Study. AB - OBJECTIVES: Youth weight perceptions and the association with weight-control intentions were explored by sex and body mass index (BMI). METHODS: Cross sectional analyses (frequency, chi-square, multiple logistic regression) were conducted among 44,861 grade 9-12 students in Year 2(Y2:2013-2014) of the COMPASS study, adjusting for sex and race/ethnicity. RESULTS: Overall, weight underestimations were more common than overestimations, although there were differences by sex and race/ethnicity. Boys were relatively more likely to underestimate their weight status, and girls were more likely to overestimate. Compared to youth with normal-weight BMIs, students with overweight BMIs were more inclined to underestimate their weight, and those with BMIs in the obese range had higher odds of accurately perceiving their weight. Regardless of BMI, youth with overweight perceptions were more likely to report trying to lose weight than those who perceived their weight to be "about right," whereas youth with underweight perceptions tended to report efforts to gain weight. CONCLUSIONS: While youth with overweight BMIs did not necessarily perceive their weight as such, accurate perceptions were more likely once BMI reached the obese range. Results suggest weight perception is a more useful predictor of weight control intentions than self-reported weight status among youth. PMID- 27561865 TI - Limited Access to Healthcare among Hispanics in the US-Mexico Border Region. AB - OBJECTIVE: Using large national databases, we investigated how living in the US Mexico border region further limited access to healthcare among the non-elderly Hispanic adult population after controlling individual and county-level characteristics. METHODS: The 2008-2012 individual-level data of non-elderly Hispanic adults from the Behavioral Risk Factor Surveillance System (BRFSS) were merged with county-level data from Area Health Resources File (AHRF). Multivariate logistic analyses were performed to predict insurance status and access to doctors using residency in the US-Mexico border region as the key predictor, adjusting individual and county-level factors. RESULTS: Controlling only individual characteristic, Hispanics living in the US-Mexico border region had significantly lower odds of having health insurance (adjusted odds ratio [AOR] = 0.51; 95% confidence interval [CI], 0.49-0.54) and access to doctors (AOR = 0.69; 95% CI, 0.66-0.72). After including county-level measurements of healthcare system capacity and other local characteristics, the border region continued to be associated with lower likelihood of healthcare access. CONCLUSION: Hispanic residents in the U.S.-Mexico border had less access to healthcare than their inland counterparts. The findings highlight unique features in this region and support policies and initiatives to improve minority healthcare access, particularly among disadvantaged populations in this region. PMID- 27561866 TI - Cooking Up Energy with Predominately Latino Children during Afterschool Hours. AB - OBJECTIVES: We investigated the impact on body weight status and food-related behaviors following participation in the Cooking Up Energy(r) (CUE) Program. METHODS: Children 7-11 years old attended 10 cooking/nutrition education sessions. Baseline and post-program weight, height and waist circumference measurements, frequency of participation in meal preparation and food frequency questionnaires were obtained. Data were analyzed for the entire group as well as a subgroup of overweight and obese participants. RESULTS: Participants (N = 51) were predominately Latino (76%) and overweight (52%). Significant reduction in mean body mass index (BMI) percentile was found in the subgroup of overweight and obese participants (N = 27; p < .05). However, reduction in mean BMI z-score was non-significant. Reports of program enjoyment (98%) and an increased desire to cook more frequently at home (83%) were found; however, no significant increase in participation in meal preparation at home was found following program completion. CONCLUSION: The CUE program was well received by most participants, and there is indication that program participation has the potential to have a positive influence on body weight. However, more research is needed to explore ways to promote an increase in participation in food preparation at home by children. PMID- 27561867 TI - Unsupportive Social Interactions are Associated with Poorer Self-reported Health in Israeli Patients with Diabetes. AB - OBJECTIVES: Social support is associated with improved adherence to treatment recommendations among patients with diabetes. This research examines negative dimensions of social support such as interference and insensitivity which may interfere with appropriate lifestyle choices. METHODS: A telephone survey in Israel of 764 patients with type 1 and type 2 diabetes was conducted to assess social support and unsupportive social interactions, and correlate them with self reported current health status. RESULTS: Patients with higher levels of interference reported poorer health after adjusting for other factors including positive social support. Interference, which is a negative dimension of social support, was higher among Arabs than Jews (OR=2.12; 95% CI: 1.44, 3.10) after adjusting for factors, including positive social support, in a logistic regression model. Among Jews, the less educated, those not performing physical activity, and those with lower levels of social support reported significantly higher levels of interference. Insensitivity was lower among Arabs compared to Jews (OR=0.64, 95%CI: 0.44, 0.94) after adjusting for the variables in the regression model. CONCLUSIONS: Unsupportive social interactions can hamper adoption of a lifestyle needed for diabetes management, negatively influencing self-reported health. PMID- 27561868 TI - Application of the Smokeless Tobacco Expectancies Questionnaire to Snus. AB - OBJECTIVE: Measures of consumer perceptions of emerging tobacco products are needed for understanding the potential for product adoption and use. The purpose of this research was to evaluate the applicability of the Smokeless Tobacco Expectancies Questionnaire to snus, and examine its association with interest in using snus. METHODS: We recruited 116 adolescents (14-17 years of age), 463 young adults (18-34 years of age), and 596 older adults (35-65 years of age) from a Web based opt-in panel. Participants completed a 10-item Snus Expectancies Questionnaire and questions about their interest in trying snus in the next month. RESULTS: Confirmatory factor analysis supported a latent factor structure representing Positive Reinforcement (PR) and Negative Health Consequences (NHC) within each age group. The scales differentiate smokers and smokeless tobacco users and nonusers. Each scale was associated with interest in purchasing snus for younger (PR: OR 1.90; NHC: OR 0.66) and older (PR: OR 1.36; NHC: OR 0.69) adults controlling for tobacco use status. CONCLUSIONS: The modified Smokeless Tobacco Expectancies Questionnaire is a valid measure of snus-related outcome expectancies, which are in turn, associated with self-reported tobacco use, and may help to identify groups who are susceptible to snus initiation and use. PMID- 27561869 TI - Tobacco and Other Drug Use among Foster Care Adolescents in West Virginia. AB - OBJECTIVES: This study presents tobacco and other drug use prevalence data from a statewide health screening program of foster care (FC) children in West Virginia, and explores associations with demographic and placement variables. METHODS: Logistic regression analyses adjusted for age, sex, and body mass index were conducted to determine if placement type and geographic region were associated with tobacco and other drug use among FC adolescents screened in 2012-2013 by the Early Periodic Screening Diagnosis and Treatment (EPSDT), or HealthCheck WV. RESULTS: One-third of the 12-17 year-olds used tobacco and 24% used other drugs. Results from the logistic regression analyses showed that significant associations between tobacco and drug use and placement variables persisted after controlling for covariates. Adolescents in home placements were significantly less likely to use tobacco (AOR=0.294; 95% CI: 0.196-0.441) or drugs (AOR=0.269; 95%, CI: 0.164-0.443) than those in agency placements. Details of significant regional variations also are presented. CONCLUSIONS: This study provides evidence of tobacco and drug use in West Virginia's FC adolescents and highlights a need for appropriate interventions for this vulnerable population. PMID- 27561870 TI - The Effect of Re-randomization in a Smoking Cessation Trial. AB - OBJECTIVES: The purpose of this sub-study was to determine whether operating engineers (heavy equipment operators) who failed to quit smoking in a randomized controlled trial would benefit from re-exposure to the interventions one year later. METHODS: Operating Engineers attending workplace safety training groups during the winters of 2010 to 2012 were randomized by training group to either to the Tobacco Tactics Web-based intervention or the 1-800-QUIT-NOW telephone line. Of the 145 original participants, 41 reappeared in training groups one year later and were re-randomized with their group. Seven-day point prevalence quit rates at 30-days and 6-months post-intervention were analyzed using the chi-square test and Fisher's exact test. RESULTS: At 30-day follow-up, an additional 9.8% (4/41) of repeaters had quit smoking. At 6-month follow-up, 12.2% (5/41) of repeaters had quit smoking. At 30-day follow-up, increased quitting was more common among those re-randomized to the intervention group than among those who received the control treatment, although this was not statistically significant and was no longer true at 6-month follow-up. CONCLUSIONS: Because many smokers make multiple attempts to quit smoking, re-enrollment of participants in smoking cessation trials may produce additional quitters. PMID- 27561871 TI - Explaining the Aerobic Exercise Intention-behavior Gap in Cancer Survivors. AB - OBJECTIVES: We sought to quantify the aerobic exercise intention-behavior gap in hematologic cancer survivors (HCS), and examine the correlates of intention formation and translation using the multi-process action control framework. METHODS: HCS (N = 606) completed a survey reporting their aerobic exercise motivation and behavior. The correlates of intention formation and translation were analyzed using separate logistic regressions. RESULTS: Overall, 71% (N = 428/606) of HCS intended to do aerobic exercise, 44% (N = 267/606) met aerobic exercise guidelines, and 60% of intenders (N = 256/428) translated their intention into aerobic exercise. Attitude (OR = 1.9), perceived control (OR = 1.5), younger age (OR = 2.0), and higher education (OR = 2.1) explained intention formation (all ps <= .001). A sense of obligation/regret (OR = 2.8), self regulation over alternative activities (OR = 1.6), attitude (OR = 2.0), perceived control (OR = 1.7), planning (OR = 1.7), being female (OR = 2.0), and younger (OR = 3.0) explained intention translation (all ps < .005). CONCLUSIONS: Forming an intention is insufficient for many HCS to meet aerobic exercise guidelines. Interventions targeting the determinants of both intention formation and translation may be most effective in promoting aerobic exercise in cancer survivors. PMID- 27561873 TI - WITHDRAWN: 2016 Recipient ACC Distinguished Cytogeneticist Award: Kathleen W. Rao, PhD, FACMG. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27561872 TI - The use of rapid review methods in health technology assessments: 3 case studies. AB - BACKGROUND: Rapid reviews are of increasing importance within health technology assessment due to time and resource constraints. There are many rapid review methods available although there is little guidance as to the most suitable methods. We present three case studies employing differing methods to suit the evidence base for each review and outline some issues to consider when selecting an appropriate method. METHODS: Three recently completed systematic review short reports produced for the UK National Institute for Health Research were examined. Different approaches to rapid review methods were used in the three reports which were undertaken to inform the commissioning of services within the NHS and to inform future trial design. We describe the methods used, the reasoning behind the choice of methods and explore the strengths and weaknesses of each method. RESULTS: Rapid review methods were chosen to meet the needs of the review and each review had distinctly different challenges such as heterogeneity in terms of populations, interventions, comparators and outcome measures (PICO) and/or large numbers of relevant trials. All reviews included at least 10 randomised controlled trials (RCTs), each with numerous included outcomes. For the first case study (sexual health interventions), very diverse studies in terms of PICO were included. P-values and summary information only were presented due to substantial heterogeneity between studies and outcomes measured. For the second case study (premature ejaculation treatments), there were over 100 RCTs but also several existing systematic reviews. Data for meta-analyses were extracted directly from existing systematic reviews with new RCT data added where available. For the final case study (cannabis cessation therapies), studies included a wide range of interventions and considerable variation in study populations and outcomes. A brief summary of the key findings for each study was presented and narrative synthesis used to summarise results for each pair of interventions compared. CONCLUSIONS: Rapid review methods need to be chosen to meet both the nature of the evidence base of a review and the challenges presented by the included studies. Appropriate methods should be chosen after an assessment of the evidence base. PMID- 27561874 TI - WITHDRAWN: Scientific Program. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27561875 TI - WITHDRAWN: 2016 American Cytogenetics Conference. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27561876 TI - WITHDRAWN: 44th Biennial American Cytogenetics Conference. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27561879 TI - American Society of Nuclear Cardiology and Society of Nuclear Medicine and Molecular Imaging Joint Position Statement on the Clinical Indications for Myocardial Perfusion PET. PMID- 27561878 TI - Highly Increased 125I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst2 Targeting in Human Cancers. AB - : There is recent in vitro and in vivo evidence that somatostatin receptor subtype 2 (sst2) antagonists are better tools to target neuroendocrine tumors (NETs) than sst2 agonists. Indeed, antagonists bind to a greater number of sst2 sites than agonists. Whether sst2 antagonists could be used successfully to target non-NETs, expressing low sst2 density, is unknown. Here, we compare quantitatively 125I-JR11 sst2 antagonist binding in vitro with that of the sst2 agonist 125I-Tyr3-octreotide in large varieties of non-NET and NET. METHODS: In vitro receptor autoradiography was performed with 125I-JR11 and 125I-Tyr3 octreotide in cancers from prostate, breast, colon, kidney, thyroid, and lymphoid tissues as well as NETs as reference. RESULTS: In general, 125I-JR11 binds to many more sst2 sites than 125I-Tyr3-octreotide. In 13 breast cancers, 8 had a low binding (mean density, 844 +/- 168 dpm/mg of tissue) with the agonist whereas 12 had a high binding (mean density, 4,447 +/- 1,128 dpm/mg of tissue) with the antagonist. All 12 renal cell cancers showed a low binding of sst2 with the agonist (mean density, 348 +/- 49 dpm/mg of tissue) whereas all cases had a high sst2 binding with the antagonist (mean density, 3,777 +/- 582 dpm/mg of tissue). One of 5 medullary thyroid cancers was positive with the agonist, whereas 5 of 5 were positive with the antagonist. In 15 non-Hodgkin lymphomas, many more sst2 sites were labeled with the antagonist than with the agonist. In 14 prostate cancers, none had sst2 binding with the agonist and only 4 had a weak binding with the antagonist. None of 17 colon cancers showed sst2 sites with the agonist, and only 3 cases were weakly positive with the antagonist. In the various tumor types, adjacent sst2-expressing tissues such as vessels, lymphocytes, nerves, mucosa, or stroma were more strongly labeled with the antagonist than with the agonist. The reference NET cases, incubated with a smaller amount of tracer, were also found to have many more sst2 sites measured with the antagonist. CONCLUSION: All renal cell cancers and most breast cancers, non-Hodgkin lymphomas, and medullary thyroid cancers represent novel indications for the in vivo radiopeptide targeting of sst2 by sst2 antagonists, comparable to NET radiotargeting with sst2 agonists. PMID- 27561877 TI - Baicalein induces CD4(+)Foxp3(+) T cells and enhances intestinal barrier function in a mouse model of food allergy. AB - The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID- 27561880 TI - Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1 Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using 11C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging. AB - : HTLV-1-associated myelopathy (HAM; HTLV-1 is human T-lymphotropic virus type 1) is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic cord. Tissue damage is attributed to the cellular immune response to HTLV-1-infected lymphocytes. The brains of HTLV-1-infected patients, with and without HAM but no clinical evidence of brain involvement, were examined using a specific 18-kDa translocator protein ligand, 11C-PBR28, and T1-weighted and diffusion-weighted MRI. METHODS: Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigen antigen D related expression on circulating CD8+ lymphocytes. 11C-PBR28 PET and MRI were performed on the same day. 11C-PBR28 PET total volume of distribution and distribution volume ratio (DVR) were estimated using 2-tissue-compartment modeling. MRI data were processed using tools from the FMRIB Software Library to estimate mean diffusivity (MD) and gray matter (GM) fraction changes. The results were compared with data from age-matched healthy volunteers. RESULTS: Across the whole brain, the total volume of distribution for the subjects with HAM (5.44 +/- 0.84) was significantly greater than that of asymptomatic carriers (3.44 +/- 0.80). The DVR of the thalamus in patients with severe and moderate HAM was higher than that in the healthy volunteers, suggesting increased translocator protein binding (z > 4.72). Subjects with more severe myelopathy and with high DR expression on CD8+ lymphocytes had increased DVR and MD (near-significant correlation found for the right thalamus MD: P = 0.06). On the T1-weighted MRI scans, the GM fraction of the brain stem was reduced in all HTLV-1-infected patients compared with controls (P < 0.001), whereas the thalamus GM fraction was decreased in patients with HAM and correlated with the disease severity. There was no correlation between neurocognitive function and these markers of central nervous system inflammation. CONCLUSION: This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain, which can be detected and monitored by 11C-PBR28 PET together with structural and diffusion weighted MRI. PMID- 27561881 TI - In Vivo Dynamic Metabolic Changes After Transplantation of Induced Pluripotent Stem Cells for Ischemic Injury. AB - : This study aimed to investigate in vivo dynamic metabolic changes after transplantation of induced pluripotent stem cells (iPSCs) and iPSC-derived enriched cardiomyocytes (iPSC-CMs) in a rat model of ischemic injury. METHODS: Serial 18F-FDG PET, echocardiographic, immunohistochemical, and immunofluorescence studies were performed after transplantation of iPSCs and iPSC CMs and compared with embryonic stem cells (ESCs), ESC-CMs, and a phosphate buffered saline control group of rats with myocardial infarction. RESULTS: Increased glucose metabolism in periinfarct areas and improved myocardial function were observed in the stem cell transplantation groups compared with the control group, and serial immunofluorescence and immunohistochemical results exhibited the survival and migration of stem cells during the study period. CONCLUSION: Serial 18F-FDG PET and echocardiographic imaging studies demonstrated the dynamic metabolic changes and recovery of myocardial function after stem cell transplantation. 18F-FDG PET could be a potential approach to evaluating spatiotemporal dynamic metabolic changes in vivo after transplantation of iPSCs or iPSC-CMs for ischemic injury. PMID- 27561882 TI - Risk of Hodgkin lymphoma according to immigration status and origin: a migrant cohort study of 2.3 million Jewish Israelis. AB - Hodgkin Lymphoma (HL), a common early adulthood malignancy, has a complex etiology. We conducted a migrant cohort study to assess immigration status and origin as predictors of HL in Israel, which has among the highest rates of HL worldwide. Nationwide data on 2,285,009 16-19-year-old Jewish adolescents, collected from 1967-2011, were linked to Israel's Cancer Registry to obtain the incidence of HL until 2012. Two thousand and ninety-three HL cases were detected during 47.0 million person-years of follow-up. Using multivariable-adjusted Cox proportional hazards modeling, risk was higher for Israeli-born compared to immigrants, similarly across origin groups (HR = 1.59; 95%CI 1.32-1.92 for the dominant nodular sclerosis subtype). Risk of HL was greater for more recent year of birth, higher BMI, taller stature, and apparently for women. These findings suggest that exposure to as yet unidentified elements of the Israeli environment increase the risk of nodular sclerosis HL, and should aid in directing research efforts. PMID- 27561883 TI - Mild photothermal therapy/photodynamic therapy/chemotherapy of breast cancer by Lyp-1 modified Docetaxel/IR820 Co-loaded micelles. AB - Patients suffering from cancer have benefited from combination therapy. Nanocarriers are the ideal candidates for combination therapy. In this study, we constructed docetaxel (DTX) loaded micellar nanomedicines co-loaded with near infrared (NIR) dye-IR820 for photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy of breast cancer. Lyp-1, a tumor homing peptide, was introduced into the nanosystems to construct the active targeting nanomedicine. In order to deliver IR820 to the tumor site and overcome its short lifetime in vivo, a PEI derivative-PCL-g-PEI was introduced. IR820 with negative charge was formed stable static interaction with the amine groups, meanwhile, the absorption of IR820 in the NIR region was weakened. It indicated that the nanosystem constructed in this study may provide an alternative candidate for mild PTT. By the evaluation of the photothermal conversion in vivo, we can confirm that IR820 has been successfully delivered and effectively accumulated in the tumor site. Furthermore, the tumor cells targeting and anticancer performances of this nanosystem have been studied in vitro and in vivo. The results demonstrated Lyp-1 modification has enhanced the tumor targeting delivery of DTX and IR820. By combining PTT and PDT, DTX nanomedicine efficiently inhibited the growth and metastasis of breast cancer in mice. This nanosystem is a promising candidate for combination therapy of breast cancer. PMID- 27561884 TI - Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity, biocompatibility and gene transfection capability. AB - There is an increasing demand in developing of multifunctional materials with good antibacterial activity, biocompatibility and drug/gene delivery capability for next-generation biomedical applications. To achieve this purpose, in this work series of hydroxyl-rich hyperbranched polyaminoglycosides of gentamicin, tobramycin, and neomycin (HP and SS-HP with redox-responsive disulfide bonds) were readily synthesized via ring-opening reactions in a one-pot manner. Both HP and SS-HP exhibit high antibacterial activity toward Escherichia coli and Staphylococcus aureus. Meanwhile, the hemolysis assay of the above materials shows good biocompatibility. Moreover, SS-HPs show excellent gene transfection efficiency in vitro due to the breakdown of reduction-responsive disulfide bonds. For an in vivo anti-tumor assay, the SS-HP/p53 complexes exhibit potent inhibition capability to the growth of tumors. This study provides a promising approach for the design of next-generation multifunctional biomedical materials. PMID- 27561885 TI - Recent advances in different modal imaging-guided photothermal therapy. AB - Photothermal therapy (PTT) has recently attracted considerable attention owing to its controllable treatment process, high tumour eradication efficiency and minimal side effects on non-cancer cells. PTT can melt cancerous cells by localising tissue hyperthermia induced by internalised therapeutic agents with a high photothermal conversion efficiency under external laser irradiation. Numerous in vitro and in vivo studies have shown the significant potential of PTT to treat tumours in future practical applications. Unfortunately, the lack of visualisation towards agent delivery and internalisation, as well as imaging guided comprehensive evaluation of therapeutic outcome, limits its further application. Developments in combined photothermal therapeutic nanoplatforms guided by different imaging modalities have compensated for the major drawback of PTT alone, proving PTT to be a promising technique in biomedical applications. In this review, we introduce recent developments in different imaging modalities including single-modal, dual-modal, triple-modal and even multi-modal imaging guided PTT, together with imaging-guided multi-functional theranostic nanoplatforms. PMID- 27561886 TI - Portal vein aneurysm and portal biliopathy. AB - Highlight Kurtcehajic and colleagues present a rare case of congenital portal vein aneurysm (PVA) with biliopathy. Symptoms associated with PVA occur in less than 10% of cases. Imaging modalities showed the PVA partially compressing the common and right hepatic ducts. Conservative treatment markedly lowered bilirubin levels and relieved the abdominal pain. PMID- 27561887 TI - Satellite-based characterization of climatic conditions before large-scale general flowering events in Peninsular Malaysia. AB - General flowering (GF) is a unique phenomenon wherein, at irregular intervals, taxonomically diverse trees in Southeast Asian dipterocarp forests synchronize their reproduction at the community level. Triggers of GF, including drought and low minimum temperatures a few months previously has been limitedly observed across large regional scales due to lack of meteorological stations. Here, we aim to identify the climatic conditions that trigger large-scale GF in Peninsular Malaysia using satellite sensors, Tropical Rainfall Measuring Mission (TRMM) and Moderate Resolution Imaging Spectroradiometer (MODIS), to evaluate the climatic conditions of focal forests. We observed antecedent drought, low temperature and high photosynthetic radiation conditions before large-scale GF events, suggesting that large-scale GF events could be triggered by these factors. In contrast, we found higher-magnitude GF in forests where lower precipitation preceded large scale GF events. GF magnitude was also negatively influenced by land surface temperature (LST) for a large-scale GF event. Therefore, we suggest that spatial extent of drought may be related to that of GF forests, and that the spatial pattern of LST may be related to that of GF occurrence. With significant new findings and other results that were consistent with previous research we clarified complicated environmental correlates with the GF phenomenon. PMID- 27561888 TI - The empirical evidence that does not support cultural group selection models for the evolution of human cooperation. AB - I outline key empirical evidence from my research and that of other scholars, testing the role of cultural group selection (CGS) in the evolution of human cooperation, which Richerson et al. failed to mention and which fails to support the CGS hypothesis. PMID- 27561889 TI - The what, how much, and when of study strategies: comparing intended versus actual study behaviour. AB - The study behaviours of students can be assessed from several perspectives, such as what study strategies are used, the total number of hours of study, and the distribution of studying over time. Here, we present the results of a survey study that considered each of these perspectives by asking students to report the what, how much, and when of their study behaviours over the course of a semester. As important, to better understand students' use of study strategies, we also had students report at the beginning of the semester how they intended to study and their beliefs about the effectiveness of a variety of common strategies. Our results indicate that during the semester, students rely on relatively ineffective strategies and mass their studying the day or two before an exam. However, students intended to begin studying earlier and to use a mix of effective and ineffective study habits. Despite their use of some ineffective strategies, they did have a relatively accurate assessment of which strategies were less versus more effective. Taken together, our results suggest that students have some excellent intentions but may falter because massing study the evening before an exam limits their use of more effective study strategies. PMID- 27561890 TI - Establishment of primary bovine intestinal epithelial cell culture and clone method. AB - The aim of this study was to establish bovine intestinal epithelial cell (BIEC) line and provide a novel clone cell method. Although various strategies of bovine cell culture and clone techniques have been reported, these methods remain not established. Here, we culture successfully primary BIECs and establish a novel clone cell method. Our result showed that BIECs could be successfully cultured and passaged about generation 5. These cellular aggregates and clusters were adherent loosely at day 2 of culture. Cell aggregates and clusters start to proliferate after approximately 4 d. The BIECs showed positive reaction against cytokeratin 18, E-cadherin, and characteristics of epithelial-like morphology. In addition, the fatty acid-binding proteins (FABPs), villin, and intestinal peptidase (IP) band were positive in BIECs. Our results suggest that the establishment of culturing and clone BIEC methods will apply to isolate and clone other primary cells. These BIECs could therefore contribute to the study of bovine intestinal nutrient absorption and regulation, immune regulation, and the pathogenesis of the bovine intestinal disease, which will provide intestinal cell model in vitro. PMID- 27561892 TI - A Cross-Linking Succinonitrile-Based Composite Polymer Electrolyte with Uniformly Dispersed Vinyl-Functionalized SiO2 Particles for Li-Ion Batteries. AB - A cross-linking succinonitrile (SN)-based composite polymer electrolyte (referred to as "CLPC-CPE"), in which vinyl-functionalized SiO2 particles connect with trimethylolpropane propoxylate triacrylate (TPPTA) monomers by covalent bonds, was prepared by an ultraviolet irradiation (UV-curing) process successfully. Vinyl-functionalized SiO2 particles may react with TPPTA monomers to form a cross linking network within the SN-based composite polymer electrolyte under ultraviolet irradiation. Vinyl-functionalized SiO2 particles as the fillers of polymer electrolyte may improve both the thermal stability of CLPC-CPE and interfacial compatibility between CLPC-CPE and electrodes effectively. There is no weight loss for CLPC-CPE until above 230 degrees C. The ionic conductivity of CLPC-CPE may reach 7.02 * 10(-4) S cm(-1) at 25 degrees C. CLPC-CPE has no significant oxidation current until up to 4.6 V (vs Li/Li(+)). The cell of LiFePO4/CLPC-CPE/Li has presented superior cycle performance and rate capability. The cell of LiFePO4/CLPC-CPE/Li may deliver a high discharge capacity of 154.4 mAh g(-1) at a rate of 0.1 C after 100 charge-discharge cycles, which is similar than that of the control cell of LiFePO4/liquid electrolyte/Li. Furthermore, the cell of LiFePO4/CLPC-CPE/Li can display a high discharge capacity of 112.7 mAh g( 1) at a rate of 2 C, which is higher than that of the cells assembled with other plastic crystal polymer electrolyte reported before obviously. PMID- 27561891 TI - Effects of tetraploidy induction on rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) proteome at early stages of development. AB - The aim of the present study was to examine the effects of tetraploidy induction on proteome of rainbow trout during the early stages of development. After insemination, the eggs were incubated at 10 degrees C for 350min. Thereafter, half of the eggs were exposed to a heat-shock of 28 degrees C for 10min. The remainder were incubated normally and used as diploid controls. Fertilized egg specimens were selected 390min post-fertilization. Samples corresponding respectively to eyed embryos and fry stages were also taken on days 18 and 76 post-fertilization. Based on two-dimensional electrophoresis, all spots that were found to differ significantly in abundance between the untreated and heat-shock treated groups were selected for identification using MALDI-TOF/TOF mass spectrometry. Out of 19 protein spots showing altered abundance in the present study, 13 spots were successfully identified. Of the spots that were shown to change in abundance in the fertilized eggs with heat-shock treatment, three were identified as vitellogenin (spots 1, 2 and 3); while the others were creatine kinase (spot 5) and nucleoside diphosphate kinase (spot 6). All of the proteins identified in the embryos were related to vitellogenin (spots 8, 12 and 13). Among the identified spots from the fry muscle extracts, two were identified as beta-globin (spots 14 and 17); while the others were parvalbumin (spots 15 and 16) and creatine kinase (spot 19). The results obtained in our study may now set the ground for investigations on gene regulation and proteome modifications in polyploid fish. PMID- 27561893 TI - The occurrence of Salmonella spp. in duck eggs on sale at retail or from catering in England. AB - : Since 2010, human salmonellosis outbreaks in the UK have been detected as associated with the consumption of duck eggs. Little data are available on the rate of occurrence of Salmonella in duck eggs. The aim of this study was to investigate the occurrence of Salmonella spp. in duck eggs on sale and from catering in England during 2011, particularly those from small-scale production. All samples were collected independently of human salmonellosis outbreak investigations. Composite samples of 6-10 eggs (shells and contents were examined separately) were examined for the presence of Salmonella spp. using the ISO 6579:2002 method. Salmonella spp. was recovered from two of 145 samples (1.4%). In one sample, Salmonella Typhimurium DT 8 was isolated from the shells while Salm. Typhimurium DT 8 and Salm. Typhimurium DT30 were isolated from the contents. Salmonella Typhimurium DT8 was isolated from the egg shells only in the second contaminated sample. This study provides baseline data for risk assessors, regulators and the food industry and may be helpful in communicating risks associated with the consumption of this product as well as evaluating risk management options to control food safety including vaccination of ducks. SIGNIFICANCE AND IMPACT OF THE STUDY: Human salmonellosis outbreaks in England and Northern Ireland due to Salmonella enterica serovar Typhimurium definitive phage type (DT) 8 have been identified as associated with the consumption of duck eggs since 2010. This study has shown that Salmonella spp. was detected in 1.4% of ducks egg samples providing baseline data for risk assessors, regulators and the food industry. This may be helpful in communicating risks associated with the consumption of this product as well as evaluating risk management options to control food safety including vaccination of ducks. PMID- 27561896 TI - Genetic support for the causal role of insulin in coronary heart disease. AB - AIMS/HYPOTHESIS: Epidemiological studies have identified several traits associated with CHD, but few of these have been shown to be causal risk factors and thus suitable targets for treatment. Our aim was to evaluate the causal role of a large set of known CHD risk factors using single-nucleotide polymorphisms (SNPs) as instrumental variables. METHODS: Based on published genome-wide association studies (GWASs), we estimated the associations between the established risk factors (blood lipids, obesity, glycaemic traits and BP) and CHD with two complementary approaches: (1) using summary statistics from GWASs to analyse the accordance of SNP effects on risk factors and on CHD; and (2) individual-level analysis where we constructed genetic risk scores (GRSs) in a large Finnish dataset (N = 26,554, CHD events n = 4016). We used a weighted regression-based method for summary-level data to evaluate the causality of risk factors. The associations between the GRSs and CHD in the Finnish dataset were evaluated with logistic and conditional logistic regression models. RESULTS: The summary-level data analysis revealed causal effects between glycaemic traits (insulin and glucose) and CHD. The individual-level data analysis supported the causal role of insulin, but not of glucose, on CHD. The GRS for insulin was associated with CHD in the Finnish cohort (OR 1.06 per SD in GRS, 95% CI 1.02, 1.10, p = 0.002). CONCLUSIONS/INTERPRETATION: These results support the causal role of insulin in the pathogenesis of CHD. Efficient treatment and prevention of insulin resistance is essential to prevent future CHD events. PMID- 27561897 TI - Deep sexual dimorphism in adult medaka fish liver highlighted by multi-omic approach. AB - Sexual dimorphism describes the features that discriminate between the two sexes at various biological levels. Especially, during the reproductive phase, the liver is one of the most sexually dimorphic organs, because of different metabolic demands between the two sexes. The liver is a key organ that plays fundamental roles in various physiological processes, including digestion, energetic metabolism, xenobiotic detoxification, biosynthesis of serum proteins, and also in endocrine or immune response. The sex-dimorphism of the liver is particularly obvious in oviparous animals, as the female liver is the main organ for the synthesis of oocyte constituents. In this work, we are interested in identifying molecular sexual dimorphism in the liver of adult medaka fish and their sex-variation in response to hepatotoxic exposures. By developing an integrative approach combining histology and different high-throughput omic investigations (metabolomics, proteomics and transcriptomics), we were able to globally depict the strong sexual dimorphism that concerns various cellular and molecular processes of hepatocytes comprising protein synthesis, amino acid, lipid and polysaccharide metabolism, along with steroidogenesis and detoxification. The results of this work imply noticeable repercussions on the biology of oviparous organisms environmentally exposed to chemical or toxin issues. PMID- 27561899 TI - Ultrasociality and the division of cognitive labor. AB - Gowdy & Krall describe the development of ultrasociality in terms of economics and the division of labor. We propose that the division of cognitive labor allows humans to behave in an ultrasocial manner without the radical evolutionary changes that are experienced by other species, suggesting that species may traverse different paths to achieve ultrasociality. PMID- 27561898 TI - TERT rs2736100 genotypes are associated with differential risk of myeloproliferative neoplasms in Swedish and Chinese male patient populations. AB - The telomerase reverse transcriptase (TERT) gene rs2736100_C allele has recently been shown to be associated with an increased risk for myeloproliferative neoplasms (MPNs) among Caucasians. However, it is unknown if this association is present in other ethnical populations and whether rs2736100 allele frequencies mirror the incidence of MPNs in a population. Here we genotyped TERT rs2736100 variants in 126 Swedish and 101 Chinese MPN patients and their age-, sex-, and ethnically-matched healthy controls. Healthy Chinese adults had a higher frequency of the A allele and lower frequencies of the C allele compared to Swedish counterparts (57.4 vs 47.0 % for A, 42.6 vs 53.0 % for C, P = 0.006). Both Swedish and Chinese patients harbored significantly higher C allele frequency than their controls (62.7 vs 53.0 % and 57.4 vs 42.6 % for Swedish and Chinese, respectively, P = 0.004). Swedes and Chinese bearing the CC genotype had a significantly increased risk of MPN compared to AA carriers (OR = 2.47; 95 % CI: 1.33-4.57, P = 0.003, for Swedes, and OR = 3.45; 95 % CI: 1.52-7.85, P = 0.005, for Chinese). Further analyses showed that rs2736100_CC was associated with robustly enhanced risk in males only (CC vs AA, OR = 5.11; 95 % CI: 2.19 11.92, P < 0.0001). The CC-carrying MPN patients exhibited significantly higher TERT expression than patients with the AC genotype. Collectively, the rs2736100_C is a risk allele for MPNs in Swedish and Chinese males, and the lower incidence of MPNs in the Chinese population is correlated with a lower rs2736100_C risk allele frequency. PMID- 27561900 TI - A registration problem for functional fingerprinting. AB - Functional fingerprints aggregate over heterogeneous tasks, protocols, and controls. The appearance of functional diversity might be explained by task heterogeneity and conceptual imprecision. PMID- 27561901 TI - Comparison of two cooling protocols for llama semen: with and without collagenase and seminal plasma in the medium. AB - Seminal plasma (SP) of South American Camelids could interfere with the interaction of spermatozoa with the extenders; therefore it becomes necessary to improve semen management using enzymatic treatment. Our objective was to compare two cooling protocols for llama semen. Twelve ejaculates were incubated in 0.1% collagenase and then were divided into two aliquots. One was extended in lactose and egg yolk (LEY) (Protocol A: collagenase and SP present). The other aliquot was centrifuged, and the pellet was resuspended in LEY (Protocol B: collagenase and SP absent). Both samples were maintained at 5 degrees C during 24 hr. Routine and DNA evaluations were carried out in raw and cooled semen. Both cooling protocols maintained sperm viability, membrane function and DNA fragmentation, with Protocol A showing a significantly lowered total and progressive motility (p < .05) and Protocol B showing a significant increase in chromatin decondensation (p < .05). Protocol A avoids centrifugation, reducing processing times and making application in the field simpler. However, as neither protocol showed a significant superiority over the other, studies should be carried out in vivo to evaluate the effect on pregnancy rates of the presence of collagenase and SP in semen samples prior to either cooling or freeze-thawing. PMID- 27561903 TI - Corrigendum. PMID- 27561902 TI - Brief Report: Evaluation of an Intelligent Learning Environment for Young Children with Autism Spectrum Disorder. AB - Researchers are increasingly attempting to develop and apply innovative technological platforms for early detection and intervention of autism spectrum disorder (ASD). This pilot study designed and evaluated a novel technologically mediated intelligent learning environment with relevance to early social orienting skills. The environment was endowed with the capacity to administer social orienting cues and adaptively respond to autonomous real-time measurement of performance (i.e., non-contact gaze measurement). We evaluated the system with both toddlers with ASD (n = 8) as well as typically developing infants (n = 8). Children in both groups were able to ultimately respond accurately to social prompts delivered by the technological system. Results also indicated that the system was capable of attracting and pushing toward correct performance autonomously without user intervention. PMID- 27561904 TI - Geographic distribution of patients affected by Cryptococcus neoformans/Cryptococcus gattii species complexes meningitis, pigeon and tree populations in Southern Brazil. AB - Cryptococcal meningitis is mainly caused by members of the C. neoformans/C. gattii species complexes. The ecological niches of Cryptococcus species have extensively been studied, but its epidemiological relationship with meningitis cases is still unknown. In this study, we estimate the relationship between cryptococcal meningitis cases and tree and pigeon populations, the classical niches of members of C. neoformans/C. gattii sensu lato. We analysed the records of every patient whose cerebrospinal fluid culture yielded Cryptococcus spp. during the last 30 years at Clinical Hospital of Curitiba. Data about Curitiba's pigeon and tree distribution were obtained from Curitiba's Secretaries of Zoonosis and Environment archives. We used ArcGis9 software to plot the distribution of the pigeon and tree populations in this city as well as cryptococcal meningitis cases, distinguishing them according to the causal agent in C. neoformans or C. gattii s.l. In total, 489 cryptococcal cultures were documented, with 140 corresponding to patients eligible for this study (134 affected by C. neoformans s.l. and 6 by C. gattii s.l.). The map showed a relationship between C. neoformans s.l. patients and pigeon population. C. gattii s.l. patients were associated with neither tree nor pigeon populations, but lived close to large unbuilt, unforested areas. PMID- 27561905 TI - Social determinants of disability-based disadvantage in Solomon islands. AB - Development discourse widely recognises that disability is the result of economic and social processes and structures that fail to accommodate persons with disabilities. Empirical work on the relationship between disability and poverty however, conceptualize poverty through an economic resource lens in high-income countries. To address this conceptual gap this article uses a social determinants of health perspective to examine how socio-cultural, economic and political contexts shape disability-based disadvantage. This article draws upon ethnographic research and supplementary data collected using rapid assessment techniques in Solomon Islands. Findings suggest that the disability-poverty nexus and inequalities in health, wellbeing and quality of life must be understood within broader patterns of social vulnerability that are institutionalised in landownership and patterns of descent, gendered power relations and disability specific stigmas that preclude social and productive engagement . This article demonstrates how a social determinant of health perspective that closely examines lived experiences of disability provides critical analytical insights into the structural mechanisms that constitute disability-based disadvantage. This article provides foundation knowledge on which policies and further research to promote disability-inclusion and equity can be based. PMID- 27561906 TI - Automobile, construction and entertainment business sector influences on sedentary lifestyles. AB - Sedentary lifestyles contribute to premature death and health inequalities. Researchers have studied personal and community-level determinants of inactivity but few have analyzed corporate influences. To reframe the public health debate on inactivity and open new doors for public sector intervention, we conducted a scoping review of evidence from several disciplines to describe how the business and political practices of the automobile, construction, and entertainment sectors have encouraged sedentary lifestyles. In the last 50 years, these industries have found it profitable to produce motor vehicles, housing, and entertainment, which intentionally or unintentionally discourage physical activity. Ceding primary authority for policy decisions in these sectors to the market-based economy has enabled the growth of powerful lobbies that encourage and maintain sedentary lifestyles. To counteract these influences, public health and civil society need to confront more upstream economic and social determinants of sedentary lifestyles. Building on evidence from efforts to change harmful tobacco, alcohol and food industry practices, we propose the creation of research and policy agendas that contribute to public health practice that can modify corporate practices that contribute to physical, social and political environments that discourage physical activity. PMID- 27561907 TI - Use of Methylene Blue to Treat Hypovolemic Shock Followed by Ischemia-Reperfusion Injury in the Postoperative Orthotopic Liver Transplant Patient: A Case Report. AB - A 57-year-old female patient received elective liver transplant due to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma. Her preoperative Model for End-Stage Liver Disease score was 11. The total transplant ischemic time was 10 hours and 35 minutes, and the warm ischemic time was 35 minutes. Even with aggressive fluid overload and use of high concentrations of vasoactive amines, the patient developed possible primary graft dysfunction with poor response to fluids and vasopressor support, suggesting vasoplegic syndrome. On the basis of the hypothesis of vasoplegic syndrome, the patient received methylene blue intravenously (100 mg bolus for 12 h/1.5 mg/kg). The catastrophic situation was controlled. The patient's urine output markedly improved, she was subsequently weaned from vasoactive support, and mechanical ventilation was discontinued 2 days later. The patient was discharged on the 20th postoperative day. PMID- 27561908 TI - The structure proposed for apteniol D is different from that of the compound obtained by total synthesis. AB - We describe the synthesis of 4,4'-oxyneolignan, the proposed structure for naturally occurring apteniol D. The diphenyl ether moiety in 4,4'-oxyneolignan was formed via classical Ullmann ether synthesis using excess copper powder in N,N-dimethylacetamide. The spectral data of synthesised apteniol D show differences compared to those of naturally occurring apteniol D. PMID- 27561909 TI - Selective Versus Non-selective alpha-Blockade Prior to Laparoscopic Adrenalectomy for Pheochromocytoma. AB - BACKGROUND: The optimal preoperative alpha-blockade strategy is debated for patients undergoing laparoscopic adrenalectomy for pheochromocytomas. We evaluated the impact of selective versus non-selective alpha-blockade on intraoperative hemodynamics and postoperative outcomes. METHODS: We identified patients having laparoscopic adrenalectomy for pheochromocytomas from 2001 to 2015. As a marker of overall intraoperative hemodynamics, we combined systolic blood pressure (SBP) > 200, SBP < 80, SBP < 80 and >200, pulse > 120, vasopressor infusion, and vasodilator infusion into a single variable. Similarly, the combination of vasopressor infusion in the post-anesthesia care unit (PACU) and the need for intensive care unit (ICU) admission provided an overview of postoperative support. RESULTS: We identified 52 patients undergoing unilateral laparoscopic adrenalectomy for pheochromocytoma. Selective alpha-blockade (i.e. doxazosin) was performed in 35 % (n = 18) of patients, and non-selective blockade with phenoxybenzamine was performed in 65 % (n = 34) of patients. Demographics and tumor characteristics were similar between groups. Patients blocked selectively were more likely to have an SBP < 80 (67 %) than those blocked with phenoxybenzamine (35 %) (p = 0.03), but we found no significant difference in overall intraoperative hemodynamics between patients blocked selectively and non selectively (p = 0.09). However, postoperatively, patients blocked selectively were more likely to require additional support with vasopressor infusions in the PACU or ICU admission (p = 0.02). Hospital stay and complication rates were similar. CONCLUSION: Laparoscopic adrenalectomy for pheochromocytoma is safe regardless of the preoperative alpha-blockade strategy employed, but patients blocked selectively may have a higher incidence of transient hypotension during surgery and a greater need for postoperative support. These differences did not result in longer hospital stay or increased complications. PMID- 27561910 TI - Association between bone mineral density and nonalcoholic fatty liver disease in Korean adults. AB - PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is associated with various metabolic abnormalities that can increase the risk of an osteoporotic fracture. Across the few previous studies of the association between NAFLD and bone mineral density (BMD), the association was not consistent. We examined the association between BMD and NAFLD in generally healthy adults. METHODS: The subjects who visited the Seoul National University Hospital for health checkup between 2005 and 2015 were included. Men aged more than 40 and postmenopausal women were included. Lumbar spine and femoral neck (FN) BMD were measured using dual-energy X-ray absorptiometry. Liver ultrasonography was conducted to evaluate the extent of fatty changes. After excluding subjects with a secondary cause of liver disease such as heavy drinking or viral hepatitis, multivariable linear regression analysis adjusted for possible cofactors was performed to investigate the association between BMD and NAFLD. RESULTS: A total of 6634 subjects was included in this study (men:women = 3306:3328). Multivariate regression analysis revealed a significant negative association between FN BMD and NAFLD in men (beta = -0.013, p = 0.029). However, there was a positive correlation between lumbar spine BMD and NAFLD in postmenopausal women (beta = 0.022, p = 0.005). CONCLUSIONS: Moderate or severe NAFLD exerted a detrimental effect on FN BMD in men. However, moderate or severe NAFLD had a positive effect on lumbar spine BMD in postmenopausal women. Potential sex-specific differences of the effect of NAFLD on BMD need to be elucidated further. PMID- 27561912 TI - Erratum. PMID- 27561911 TI - ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD). AB - Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the basolateral compartment, which was more pronounced in cells from COPD patients than in non-COPD controls. CS transiently increased IL6R and AREG mRNA in ALI-PBEC to a similar extent in cultures from both groups, suggesting that posttranslational events determine differential shedding between COPD and non COPD cultures. We show for the first time by in situ proximity ligation (PLA) that CS strongly enhances interactions of phosphorylated ADAM17 with AREG and IL 6R in an intracellular compartment, suggesting that CS-induced intracellular trafficking events precede shedding to the extracellular compartment. Both EGFR and ADAM17 activity contribute to CS-induced IL-6R and AREG protein shedding and to mRNA expression, as demonstrated using selective inhibitors (AG1478 and TMI 2). Our data are consistent with an autocrine-positive feedback mechanism in which CS triggers shedding of EGFR agonists evoking EGFR activation, in ADAM17 dependent manner, and subsequently transduce paracrine signaling toward myeloid cells and connective tissue. Reducing ADAM17 and EGFR activity could therefore be a therapeutic approach for the tissue remodeling and inflammation observed in COPD. PMID- 27561913 TI - Transition-Metal Free Mechanochemical Approach to Polyyne Substituted Pyrroles. AB - In this contribution, the synthesis of long chain hexatriynyl- and octatetraynyl substituted pyrroles in one step from 1-halopolyyne precursors is reported. The products were obtained via a mechanochemical approach by simple grinding of 1 haloalkynes with N-substituted pyrroles and potassium carbonate which played a role of heterogeneous catalyst and this solvent- and transition metal-free approach is unprecedent in the synthesis of new, organic, long chain polyynes. Additionally, an extensive X-ray single crystal study of pyrrole end-capped polyynes is presented. Such compounds are possible substrates for different oligoheterocycles and have a significant application potential such as for instance molecular wires. PMID- 27561914 TI - Simultaneous atomic-resolution electron ptychography and Z-contrast imaging of light and heavy elements in complex nanostructures. AB - The aberration-corrected scanning transmission electron microscope (STEM) has emerged as a key tool for atomic resolution characterization of materials, allowing the use of imaging modes such as Z-contrast and spectroscopic mapping. The STEM has not been regarded as optimal for the phase-contrast imaging necessary for efficient imaging of light materials. Here, recent developments in fast electron detectors and data processing capability is shown to enable electron ptychography, to extend the capability of the STEM by allowing quantitative phase images to be formed simultaneously with incoherent signals. We demonstrate this capability as a practical tool for imaging complex structures containing light and heavy elements, and use it to solve the structure of a beam sensitive carbon nanostructure. The contrast of the phase image contrast is maximized through the post-acquisition correction of lens aberrations. The compensation of defocus aberrations is also used for the measurement of three dimensional sample information through post-acquisition optical sectioning. PMID- 27561915 TI - Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments. AB - We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice. PMID- 27561917 TI - Rapidly patterning micro/nano devices by directly assembling ions and nanomaterials. AB - The synthesis and assembly of components are key steps in micro/nano device manufacturing. In this article, we report an optically controlled assembly method that can rapidly pattern micro/nano devices by directly assembling ions and nanomaterials without expensive physical masks and complex etching processes. Utilizing this controllable process, different types of device components (e.g., metallic and semiconductor) can be fabricated and assembled in 10-30 seconds, which is far more rapid and cost-effective than any other micro/nano fabrication method. PMID- 27561916 TI - Endothelium-dependent vasodilatory signalling modulates alpha1 -adrenergic vasoconstriction in contracting skeletal muscle of humans. AB - KEY POINTS: 'Functional sympatholysis' describes the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction, and is critical to ensure proper blood flow and oxygen delivery to metabolically active skeletal muscle. The signalling mechanism responsible for sympatholysis in healthy humans is unknown. Evidence from animal models has identified endothelium-derived hyperpolarization (EDH) as a potential mechanism capable of attenuating sympathetic vasoconstriction. In this study, increasing endothelium-dependent signalling during exercise significantly enhanced the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction in humans. This is the first study in humans to identify endothelium-dependent regulation of sympathetic vasoconstriction in contracting skeletal muscle, and specifically supports a role for EDH-like vasodilatory signalling. Impaired functional sympatholysis is a common feature of cardiovascular ageing, hypertension and heart failure, and thus identifying fundamental mechanisms responsible for sympatholysis is clinically relevant. ABSTRACT: Stimulation of alpha-adrenoceptors elicits vasoconstriction in resting skeletal muscle that is blunted during exercise in an intensity dependent manner. In humans, the underlying mechanisms remain unclear. We tested the hypothesis that stimulating endothelium-dependent vasodilatory signalling will enhance the ability of contracting skeletal muscle to blunt alpha1 adrenergic vasoconstriction. Changes in forearm vascular conductance (FVC; Doppler ultrasound, brachial intra-arterial pressure via catheter) to local intra arterial infusion of phenylephrine (PE; alpha1 -adrenoceptor agonist) were calculated during (1) infusion of the endothelium-dependent vasodilators acetylcholine (ACh) and adenosine triphosphate (ATP), the endothelium-independent vasodilator (sodium nitroprusside, SNP), or potassium chloride (KCl) at rest; (2) mild or moderate intensity handgrip exercise; and (3) combined mild exercise + ACh, ATP, SNP, or KCl infusions in healthy adults. Robust vasoconstriction to PE was observed during vasodilator infusion alone and mild exercise, and this was blunted during moderate intensity exercise (DeltaFVC: -34 +/- 4 and -34 +/- 3 vs. -13 +/- 2%, respectively, P < 0.05). Infusion of ACh or ATP during mild exercise significantly attenuated PE vasoconstriction similar to levels observed during moderate exercise (ACh: -3 +/- 4; ATP: -18 +/- 4%). In contrast, infusion of SNP or KCl during mild exercise did not attenuate PE-mediated vasoconstriction (-32 +/- 5 and -46 +/- 3%). To further study the role of endothelium-dependent hyperpolarization (EDH), ACh trials were repeated with combined nitric oxide synthase and cyclooxygenase inhibition. Here, PE-mediated vasoconstriction was blunted at rest (blockade: -20 +/- 5 vs. CONTROL: -31 +/- 3% vs.; P < 0.05) and remained blunted during exercise (blockade: -15 +/- 5 vs. CONTROL: -14 +/- 5%). We conclude that stimulation of EDH-like vasodilatation can blunt alpha1 adrenergic vasoconstriction in contracting skeletal muscle of humans. PMID- 27561918 TI - Anti-inflammatory potential of black carrot (Daucus carota L.) polyphenols in a co-culture model of intestinal Caco-2 and endothelial EA.hy926 cells. AB - SCOPE: The present study was developed to determine the ability of polyphenol rich black carrot and its by-products, i.e., peel and pomace, to modulate the inflammatory response in tumor necrosis factor alpha (TNF-alpha) treated endothelial cells after gastrointestinal digestion and in a co-culture of intestinal Caco-2 and endothelial EA.hy926 cell model. RESULTS: The results indicated that after 4 h of treatment, the transport of anthocyanins and phenolic acids was higher for digested samples (1.3-7%) compared to the undigested samples (0-3.3%). The transported polyphenols were able to downregulate the secretion of pro-inflammatory markers, i.e. IL-8, monocyte chemoattractant protein 1, vascular endothelial growth factor, and intercellular adhesion molecule 1, under normal and tumor necrosis factor alpha induced inflammatory conditions. The most pronounced protective effects were observed with digested samples under inflammatory conditions, which significantly decreased the secretion of all markers from 120-203% down to 34-144% (p < 0.001). CONCLUSIONS: Overall, these results show that the polyphenol-rich black carrot absorption products may function through an inhibitory regulation of the inflammatory cascade in endothelial cells. PMID- 27561919 TI - Computational insight into complex structures of thorium coordination with N, N'- bis(3-allyl salicylidene)-o-phenylenediamine. AB - Theoretical calculations on the structure of Th(IV) complex containing N, N'- bis(3-allyl salicylidene)-o-phenylenediamine (BASPDA) were performed using density functional theory (DFT) at the B3LYP/6-311G** level. The geometrical structural parameters and infrared spectra results of the Th(BASPDA)2 from the calculation were compared with the parallel dislocated structure (PDS) obtained in laboratory. The calculated structural parameters were in good agreement with the experimental results. In addition, based on the calculations, a stereoisomer SFS (staggered finger " + " structure) of the Th(BASPDA)2 complex was forecasted by the analysis of a comprehensive method. The charge distribution, structural parameters, bond order indices, spectral properties and thermodynamic properties as well as the molecular orbitals of the two possible crystal structures of Th(BASPDA)2 were also systematically studied. It was expected that this work could provide insightful information for understanding the properties of Th (BASPDA)2 complex at the molecular level. PMID- 27561920 TI - Exploring 3D structure of human gonadotropin hormone receptor at antagonist state using homology modeling, molecular dynamic simulation, and cross-docking studies. AB - Human gonadotropin hormone receptor, a G-protein coupled receptor, is the target of many medications used in fertility disorders. Obtaining more structural information about the receptor could be useful in many studies related to drug design. In this study, the structure of human gonadotropin receptor was subjected to homology modeling studies and molecular dynamic simulation within a DPPC lipid bilayer for 100 ns. Several frames were thereafter extracted from simulation trajectories representing the receptor at different states. In order to find a proper model of the receptor at the antagonist state, all frames were subjected to cross-docking studies of some antagonists with known experimental values (Ki). Frame 194 revealed a reasonable correlation between docking calculated energy scores and experimental activity values (|r| = 0.91). The obtained correlation was validated by means of SSLR and showed the presence of no chance correlation for the obtained model. Different structural features reported for the receptor, such as two disulfide bridges and ionic lock between GLU90 and LYS 121 were also investigated in the final model. PMID- 27561921 TI - Medical Care Costs Associated With Long-term Weight Maintenance Versus Weight Gain Among Patients With Type 2 Diabetes. AB - OBJECTIVE: Weight loss is recommended for overweight patients with diabetes but avoidance of weight gain may be a more realistic goal. We calculated the 4-year economic impact of maintaining body weight versus gaining weight. RESEARCH DESIGN AND METHODS: Among 8,154 patients with type 2 diabetes, we calculated weight change as the difference between the first body weight measure in 2010 and the last measure in 2013 and calculated mean glycated hemoglobin (A1C) from all measurements from 2010 to 2013. We created four analysis groups: weight change <5% and A1C <7%; weight gain >=5% and A1C <7%; weight change <5% and A1C >=7%; and weight gain >=5% and A1C >=7%. We compared change in medical costs between 2010 and 2013, adjusted for demographic and clinical characteristics. RESULTS: Patients who maintained weight within 5% of baseline experienced a reduction in costs of about $400 regardless of A1C. In contrast, patients who gained >=5% of baseline weight and had mean A1C >=7% had an increase in costs of $1,473 (P < 0.001). Those who gained >5% of their baseline weight with mean A1C <7% had a modest increase in costs ($387, NS). CONCLUSIONS: Patients who gained at least 5% of their baseline body weight and did not maintain A1C <7% over 4 years experienced a 14% increase in medical costs, whereas those who maintained good glycemic control had a mean cost increase of 3.3%. However, patients who maintained weight within 5% of baseline had costs that were ~5% lower than baseline. Avoidance of weight gain may reduce costs in the long-term. PMID- 27561922 TI - Toward Precision Medicine: TBC1D4 Disruption Is Common Among the Inuit and Leads to Underdiagnosis of Type 2 Diabetes. AB - OBJECTIVE: A common nonsense mutation in TBC1D4 was recently found to substantially increase the odds of type 2 diabetes in Greenlandic Inuit, leading to exclusively increased postprandial glucose. We investigated the frequency and effect of the TBC1D4 mutation on glucose metabolism and type 2 diabetes diagnosis among Canadian and Alaskan Inuit. RESEARCH DESIGN AND METHODS: Exome sequencing of the TBC1D4 variant was performed in 114 Inuit from Nunavik, Canada, and Sanger sequencing was undertaken in 1,027 Alaskan Inuit from the Genetics of Coronary Artery Disease in Alaskan Natives (GOCADAN) Study. Association testing evaluated the effect of the TBC1D4 variant on diabetes-related metabolic traits and diagnosis. RESULTS: The TBC1D4 mutation was present in 27% of Canadian and Alaskan Inuit. It was strongly associated with higher glucose (effect size +3.3 mmol/L; P = 2.5 x 10-6) and insulin (effect size +175 pmol/L; P = 0.04) 2 h after an oral glucose load in homozygote carriers. TBC1D4 carriers with prediabetes and type 2 diabetes had an increased risk of remaining undiagnosed unless postprandial glucose values were tested (odds ratio 5.4 [95% CI 2.5-12]) compared with noncarriers. Of carriers with prediabetes or type 2 diabetes, 32% would remain undiagnosed without an oral glucose tolerance test (OGTT). CONCLUSIONS: Disruption of TBC1D4 is common among North American Inuit, resulting in exclusively elevated postprandial glucose. This leads to underdiagnosis of type 2 diabetes, unless an OGTT is performed. Accounting for genetic factors in the care of Inuit with diabetes provides an opportunity to implement precision medicine in this population. PMID- 27561923 TI - Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes. AB - OBJECTIVE: Insulin resistance is associated with mitochondrial dysfunction and decreased ATP synthesis. Treatment of individuals with type 2 diabetes mellitus (T2DM) with sodium-glucose transporter 2 inhibitors (SGLT2i) improves insulin sensitivity. However, recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i. The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1) mitochondrial ATP synthesis and 2) substrate oxidation rates and ketone production. RESEARCH DESIGN AND METHODS: The study randomized 18 individuals with T2DM to dapagliflozin (n = 9) or placebo (n = 9). Before and after 2 weeks, subjects received an insulin clamp with tritiated glucose, indirect calorimetry, and muscle biopsies. RESULTS: Dapagliflozin reduced fasting plasma glucose (167 +/- 13 to 128 +/- 6 mg/dL) and increased insulin-stimulated glucose disposal by 36% (P < 0.01). Glucose oxidation decreased (1.06 to 0.80 mg/kg ? min, P < 0.05), whereas nonoxidative glucose disposal (glycogen synthesis) increased (2.74 to 4.74 mg/kg ? min, P = 0.03). Dapagliflozin decreased basal glucose oxidation and increased lipid oxidation and plasma ketone concentration (0.05 to 0.19 mmol/L, P < 0.01) in association with an increase in fasting plasma glucagon (77 +/- 8 to 94 +/- 13, P < 0.01). Dapagliflozin reduced the ATP synthesis rate, which correlated with an increase in plasma ketone concentration. CONCLUSIONS: Dapagliflozin improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production. PMID- 27561924 TI - The Association Between Marijuana Usage and Discrimination Among Adult Black Men. AB - Black men may use marijuana as an externalizing coping mechanism to handle the chronic stress of discrimination. The aim of the study was to examine the relationship between everyday and major discrimination and marijuana use among a national sample of Black men. Using the National Survey of American Life, logistic regression analyses was used to determine the association between recent marijuana use and everyday discrimination, major discrimination, and a fully adjusted model that include everyday and major discrimination among adult Black men ( n = 1,833). Additionally, a multinomial logistic regression was used to examine the association between the frequency of marijuana usage and everyday discrimination and major discrimination among men who used marijuana in the past year. Everyday discrimination was not associated with marijuana use. In the fully adjusted model, men who experienced major discrimination had a higher odds of marijuana use ( OR: 1.19, 95% CI [1.05, 1.34]), than those who did not control for everyday discrimination and covariates of interest. Among recent marijuana users, men who used almost every day had a decreased risks for major discrimination (RRR: 0.72, 95% CI [0.56, 0.92]), compared with men who used less than once a month. The findings suggest that recent marijuana use among Black men is associated with experiences of major discrimination. Interestingly, men who used almost every day had a decreased risk for major discrimination. Marijuana may be used as a coping mechanism. PMID- 27561925 TI - Phosphodiesterase-5 Inhibitors and Vacuum Erection Device for Penile Rehabilitation After Laparoscopic Nerve-Preserving Radical Proctectomy for Rectal Cancer: A Prospective Controlled Trial. AB - The current study sought to clarify the role of phosphodiesterase type 5 inhibitors (PDE-5i) and a vacuum erection device (VED) in penile rehabilitation after laparoscopic nerve-preserving radical proctectomy (LNRP) for rectal cancer. Participants were assigned to one of the following arms-no-intervention, nightly use of sildenafil 25 mg for 3 months after surgery, or concurrent use of nightly sildenafil 25 mg/day for 3 months and a vacuum erection device (VED) 10 to 15 minutes/day for 3 months-in a nonrandomized fashion. All participants had a follow-up of over 12 months prospectively, and patients had baseline, 3-, 6-, and 12-month assessment based on the International Index of Erectile Function-5 (IIEF 5). Seventy-one cases were included in final analyses. In the no-intervention group, the mean baseline IIEF-5 score of 21.9 decreased rapidly to 5.0 at 3 months ( p < .001), 9.2 at 6 months ( p < .001), and stayed at 10.9 at 12 months ( p < .001). In the single therapy group, the mean baseline IIEF-5 score of 22.4 decreased dramatically to 9.0 at 3 months ( p < .001), 14.9 at 6 months ( p = .005), and stayed at 15.1 at 12 months ( p = .005). In the combined therapy group, the mean baseline IIEF-5 score of 23.0 decreased slightly to 15.0 at 3 months ( p = .005), 18.0 at 6 months ( p = .038), and maintained at 18.7 at 12 months ( p = .163). Findings suggested an over 50% decline in the quality of erection function of the patients after LNRP. The early use of PDE-5i alone or combined use of PDE-5i and VED after LNRP maintained erectile function at 12 months. PMID- 27561927 TI - PACAP Is Protective in a Rat Model of Retinopathy of Prematurity. AB - The oxygen-induced retinopathy (OIR) is a well-established rodent model of retinopathy of prematurity (ROP), which is one of the most common causes of childhood visual impairment affecting preterm babies. Pituitary adenylate cyclase activating polypeptide (PACAP) is known to have neuroprotective effects. Several studies have revealed the presence of PACAP and its receptors in the retina and reported its protective effects in ischemic and diabetic retinopathy. In this study, we investigated whether PACAP administration can influence the vascular changes in the rat OIR model. OIR was generated by placing the animals in daily alternating 10/50 oxygen concentrations from postnatal day (PD) 0 to PD14 then returned them to room air. Meanwhile, animals received PACAP or saline intraperitoneally or intravitreally from PD1 to PD8 or on PD11, PD14, and PD17, respectively. On PD19 +/- 1, the retinas were isolated and the vessels were visualized by isolectin staining. The percentage of avascular to whole retinal areas and the number of branching points were measured. Change in cytokine expression was also determined. Intravitreal treatment with PACAP remarkably reduced the extent of avascular area compared to the non- and saline-treated OIR groups. Intraperitoneal PACAP injection did not influence the vascular extent. Retinal images of room-air controls did not show vascular alterations. No changes in the number of vessel branching were observed after treatments. Alterations in cytokine profile after local PACAP injection further supported the protective role of the peptide. This is the first study to examine the effects of PACAP in ROP. Although the exact mechanism is still not revealed, the present results show that PACAP treatment can ameliorate the vascular changes in the animal model of ROP. PMID- 27561926 TI - Genetic Screening of Pediatric Cavernous Malformations. AB - Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Heterozygous loss of function mutations in CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10 genes are identified in about 90 % of familial cases of CCMs and two thirds of sporadic cases with multiple lesions. In this study, we performed genetic screening of a cohort of 31 patients, mainly pediatric. We analyzed the CCM1, CCM2, and CCM3 genes by multiplex ligation dependent probe amplification (MLPA) and direct sequencing of exons and intronic boundaries. A total of 9 typical pathogenic loss-of-function mutations were identified in 10 out 31 patients (32 %). The 75 % of familial cases were mutated and the percentage reached to 85 % when we consider only pediatric cases. Detection rate in sporadic cases with multiple lesions was considerably lower (16 %). We identified a novel variant of CCM3, the c.130-131insT (p.R45Efs*8), in 1 pediatric sporadic case with multiple lesions that introduced a premature termination codon into the messenger RNA (mRNA), most likely leading to mRNA decay. Similar to other CCM pediatric series, the main symptoms associated to clinical debut consisted of cerebral hemorrhage. In conclusion, the penetrance of CCM mutations in familial pediatric cases is high (85 %). The genetic workup could improve clinical and genetic counseling in CCM patients. Moreover, we confirmed the high risk of hemorrhage in children with CCMs. PMID- 27561928 TI - Secreted Protein Acidic and Rich in Cysteine Modulates Molecular Arterial Homeostasis of Human Arterial Smooth Muscle Cells In Vitro. AB - Secreted protein acidic and rich in cysteine (SPARC) is widely expressed in the vascular smooth muscle cells (VSMCs) of human intracranial aneurysms (IAs), but the effect and underlying mechanism of SPARC on VSMCs during the formation and progression of IAs needs to be probed. Human umbilical arterial smooth muscle cells (HUASMCs) were treated with a gradient concentrations of SPARC in vitro for different time. Cell counting kit-8 (CCK-8) assay, cell cycle, and cell apoptosis were used to investigate the effect of SPARC on HUASMCs. After exposure to 2 and 4 MUg/ml SPARC, cell viability were 89.3 +/- 2.00 %, and 87.57 +/- 2.17 % (P < 0.05 vs. control), respectively. Induced by 2 MUg/ml SPARC, the proportion of cells in G0/G1 phase was 74.77 +/- 1.33 % (P < 0.05 vs. control), and the early and late apoptosis ratio were 7.38 +/- 1.25 % and 4.86 +/- 0.81 % (P < 0.01 vs. control), respectively. After exposure to 2 MUg/ml SPARC for 2, 6, 12, 24, and 48 h, Western blot analysis showed that the protein level of p21 was upregulated significantly at 2-12 h (P < 0.05 vs. control), while the expression of p53 remained stable within 48 h. The expression of Bax protein increased markedly and peaked at 24 (P < 0.01 vs. control), while Bcl2 protein decreased significantly at 48 h (P < 0.01 vs. control). Cleaved caspase3 was also upregulated dramatically and peaked at 24 h (P < 0.05 vs. control). The protein level of MMP2 increased significantly and peaked at 24 h (P < 0.01 vs. control), while TIMP2 remained stable and even reduced at 48 h (P < 0.05 vs. control). Taken together, SPARC could arrest HUASMCs in G0/G1 phase by overexpression of p21 and induce mitochondria-mediated apoptosis in vitro, which could result in the decreased cell viability. Besides, SPARC might also lead to the activation of MMP2 instead of MMP9. These results indicated SPARC could reduce the self-repair capability and increase injury of media layer and internal elastic lamina of intracranial artery, which would disrupt the normal homeostatic mechanism controlling vascular repair, thus promoting the formation and progression of IAs. PMID- 27561931 TI - [Consensus of management of vaginal birth after cesarean (2016)]. PMID- 27561932 TI - [Guideline of operative vaginal delivery (2016)]. PMID- 27561929 TI - Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. AB - The response to hypoxia in animals involves the expression of multiple genes regulated by the alphabeta-hypoxia-inducible transcription factors (HIFs). The hypoxia-sensing mechanism involves oxygen limited hydroxylation of prolyl residues in the N- and C-terminal oxygen-dependent degradation domains (NODD and CODD) of HIFalpha isoforms, as catalysed by prolyl hydroxylases (PHD 1-3). Prolyl hydroxylation promotes binding of HIFalpha to the von Hippel-Lindau protein (VHL) elongin B/C complex, thus signalling for proteosomal degradation of HIFalpha. We reveal that certain PHD2 variants linked to familial erythrocytosis and cancer are highly selective for CODD or NODD. Crystalline and solution state studies coupled to kinetic and cellular analyses reveal how wild-type and variant PHDs achieve ODD selectivity via different dynamic interactions involving loop and C terminal regions. The results inform on how HIF target gene selectivity is achieved and will be of use in developing selective PHD inhibitors. PMID- 27561930 TI - Metadynamic metainference: Enhanced sampling of the metainference ensemble using metadynamics. AB - Accurate and precise structural ensembles of proteins and macromolecular complexes can be obtained with metainference, a recently proposed Bayesian inference method that integrates experimental information with prior knowledge and deals with all sources of errors in the data as well as with sample heterogeneity. The study of complex macromolecular systems, however, requires an extensive conformational sampling, which represents a separate challenge. To address such challenge and to exhaustively and efficiently generate structural ensembles we combine metainference with metadynamics and illustrate its application to the calculation of the free energy landscape of the alanine dipeptide. PMID- 27561934 TI - [Challenges in post-cesarean era: new issues about vaginal birth after cesarean]. PMID- 27561933 TI - [Expert opinion of diagnosis and treatment of cesarean scar pregnancy (2016)]. PMID- 27561935 TI - [Analysis of factors affecting vaginal birth after cesarean]. AB - OBJECTIVE: To investigate the factors affecting the vaginal birth after cesarean (VBAC). METHODS: Totaly 298 women who underwent trial of labor after cesarean section (TOLAC) from Jan 2015 to Dec 2015 were recruited from Beijing Obstetrics and Gynecology Hospital, FuXing Hospital, Tongzhou Maternal and Child Health Hospital of Beijing, the Second Affiliated Hospital of Chongqing Medical University and the People's Hospital of Chengyang District of Qingdao. The maternal age, the interval from the last cesarean section, the body mass index (BMI) before pregnancy, the weight gain during pregnancy, the way into labor, the Bishop score before labor, the gestational age and the birth weight of the neonate were recorded in a self-made form. The factors affecting VBAC were analyzed by univariate analysis and multivariable logistic regression. RESULTS: (1)The incidence of VBAC, uterine rupture, postpartum hemorrhage and neonatal asphyxia were 70.5% (210/298), 2.7% (8/298), 9.4% (28/298) and 1.3% (4/298), respectively. No maternal death and perinatal death occurred. (2)The univariate analysis suggested that the maternal age, the BMI before pregnancy, the Bishop score before labor, the labor induction, the gestational age at delivery and the neonatal weight were factors affecting VBAC. The maternal age and the Bishop score before labor were significantly higher in the VBAC group than in the unsuccessful TOLAC group(P<0.05). While the BMI before pregnancy, the induction rate, the gestational weeks at delivery and the birth weight of the neonate were significantly lower in the VBAC group than in the unsuccessful TOLAC group (P<0.05). Multivariable logistic regression analysis showed that successful VBAC was affected by the maternal age, the BMI before pregnancy, the Bishop score before labor and the birth weight of the neonates(P<0.05). CONCLUSION: The maternal age, the BMI before pregnancy, the Bishop score before labor and the birth weight of neonate are the main factors affecting VBAC. PMID- 27561936 TI - [Multi-centric clinical study of trial of labor after cesarean section]. AB - OBJECTIVE: To study the feasibility and safety of trial of labor after cesarean section (TOLAC). METHODS: Retrospective analysis of five medical center of Guangdong province from January 2011 to December 2015 hospitalized delivery information, compare the same scar TOLAC (research group) with the scar pregnancy (control group) pregnancy outcomes, to study the feasibility and safety of TOLAC. RESULTS: (1) During 2011-2015, total delivery 95 600 cases in five medical center, 13 824 cases of thme with uterine scar pregnancy, including 12 027 cases elective repeat cesarean section and 1 797 cases (13.00%, 1 797/13 824) with scar uterus vaginal trial of labor. Among 1 308 cases of vaginal delivery, the success for trial of labor rate was 72.79% (1 308/1 797). From 2011 to 2015, there were increased rate of pregnancy after cesarean section, which were respectively 10.71%, 13.28%, 14.45%, 15.54% and 16.98%. The will of vaginal birth were rising and the rate were respectively 11.85%, 12.25%, 13.49%, 13.82% and 12.93%. (2) There were 489 (27.21%, 489/1 797) cases of scar uterus maternal emergency cesarean section in the trial of labor, reason for "social factors" require for cesarean delivery have 68 cases, the percentage was 13.91% (68/489), compared with control group (7.18%, 206/2 869), the difference was statistically significant difference (chi(2)=27.356, P=0.000). Doctors diagnosed as "aura uterine rupture" in the labor was 11.86% (58/489), compared with that in control group (1.43%, 41/2 869), the differences were statistically significant difference (chi(2)=1 578.223, P=0.000). (3) The incidence of uterine rupture of the research group (0.74%, 9/1 211) was significantly higher than that of control group (0.01%,2/31 200; chi(2)> 2 000, P=0.000). The incidence of postpartum hemorrhage in research group was 6.94% (84/1 211), compared with that in the control group (3.05%, 951/31 200), there was statistically significant difference (chi(2)=16.328, P=0.000). While, there were no statistical significancefor the labor time limit, birth rate of severe asphyxia and neonatal birth weight average differences between two groups (P>0.05). CONCLUSIONS: The rate of pregnancy after cesarean section is increasing year by year, and the will of vaginal birth is increasing, while it still are generally low. TOLAC is safe and feasible, but also significantly higher risk, strictly labor monitoring and can proceed fast cesarean delivery in delivery room is an important guarantee of safe delivery. PMID- 27561937 TI - [Clinical study on vaginal birth after cesarean]. AB - OBJECTIVE: To investigate the incidence and pregnant outcome on vaginal birth after cesarean (VBAC). METHODS: From January 2005 to December 2015, clinical data of 507 cases with VBAC in West China Second Hospital were studied retrospectively. There were 370 cases of VBAC from January 2013 to December 2015 as study group (VBAC group), in contrast, 740 cases of elective repeat cesarean section (ERCS group) and 740 primiparas of vaginal delivery without history of cesarean section as control groups, the pregnancy outcome were analyzed between the study group and control groups respectively. RESULTS: (1) There were 76 547 total births from January 2005 to December 2015. Among these, 10 178 (13.296%, 10 178/76 547) patients had a single prior low transverse cesarean section, of which 4.981% (507/10 178) had VBAC. The incidence of VBAC was rising from 1.020%-3.704% during 2005-2012 to 6.028%-7.662% during 2013-2015. The rate of scared uterus during 2013-2015 was 18.269% (5 539/30 319), of which 9.26% (513/5 539) chose trial of labor after cesarean section (TOLAC). Successful VBAC occurred in 72.12% (370/513) of patients with TOLAC, and 27.88% (143/513) delivered by emergency cesarean. (2) The following parameters of the successful group and the unsuccessful VBAC group were compared, maternal age (29+/-4) versus (34+/-4) years, body mass index at prenatal visit (22.2+/-1.4) versus (22.6+/-1.4) kg/m(2), gestational age (38.7+/-0.9) versus (39.6+/-1.3) weeks, birth weight (3 326+/-317) versus (3 404+/-285) g, and the rate of induction of labor 0 (0/370) and 6.29% (9/143), there were significant differences (all P<0.01). There was no statistical difference between two group for lower uterine segment (P=0.947). (3) The duration of labor of VBAC group and 740 primiparas of vaginal delivery without history of cesarean section was compared, (10.3+/-1.8) versus (11.5+/ 2.0) hours, there was significant difference (P<0.01). There were no statistical difference between two groups for the following parameters, including postpartum hemorrhage, hospitalization duration, the ratio of 5-minute Apgar score>=8, neonatal admission rate (all P>0.05). (4) The postpartum hemorrhage and hospitalization duration in VBAC group incidence were respectively (194+/-34) ml and (2.32+/-0.49) days, and the indexes of the ERCS group were respectively (419+/-57) ml and (4.14+/-0.78) days, there were significant differences (all P<0.01). There were no statistical difference between two groups for the ratio of 5-minute Apgar score>=8 and neonatal admission rate (all P>0.05). CONCLUSIONS: The majority of patients choose ERCS rather than TOLAC. It's important to assess the indications and contraindications of patients for the successful VBAC, and to monitor maternal and fetal conditions during the delivery process. The premise of TOLAC is a comprehensive understanding of closely monitoring the progress of delivery. Compared with the ERCS, VBAC could reduce patients' postpartum hemorrhage and hospitalization duration, improve the outcomes of pregnancy, and the cesarean section rate could be reduced. PMID- 27561938 TI - [Application of array-based comparative genomic hybridization technique in genetic analysis of patients with spontaneous abortion]. AB - OBJECTIVE: To investigate the value of array-based comparative genomic hybridization (array-CGH) technique for the detection of chromosomal analysis of miscarried embryo, and to provide genetic counseling for couples with spontaneous abortion. METHODS: Totally 382 patients who underwent miscarriage were enrolled in this study. All aborted tissues were analyzed with conventional cytogenetic karyotyping and array-CGH, respectively. RESULTS: Through genetic analysis, all of the 382 specimens were successfully analyzed by array-CGH (100.0%, 382/382), and the detection rate of chromosomal aberrations was 46.6% (178/382). However, conventional karyotype analysis was successfully performed in 281 cases (73.6%, 281/382), and 113 (40.2%, 113/281) were found with chromosomal aberrations. Of these 178 samples identified by array-CGH, 163 samples (91.6%, 163/178) were aneuploidy, 15 samples (8.4%, 15/178) were segmental deletion and (or) duplication cases. Four of 10 cases with small segmental deletion and duplication were validated to be transferred from their fathers or mathers who were carriers of submicroscopic reciprocal translocation. Of these 113 abnormal karyotypes founded by conventional karyotyping, 108 cases (95.6%, 108/113) were aneuploidy and 5 cases (4.4%, 5/113) had chromosome structural aberrations. Most array-CGH results were consistent with conventional karyotyping but with 3 cases of discrepancy, which included 2 cases of triploids, 1 case of low-level mosaicism that undetcted by array-CGH. CONCLUSIONS: Compared with conventional karyotyping, there is an increased detection rate of chromosomal abnormalities when array-CGH is used to analyse the products of conception, primarilly because of its sucess with nonviable tissues. It could be a first-line method to determine the reason of miscarrage with higher accuracy and sensitivity. PMID- 27561939 TI - [Association between the C46T polymorphism of coagulation factor XII gene and the involvement of factor XII activity in patients with unexplained recurrent spontaneous abortion]. AB - OBJECTIVE: To explore the association between the C46T polymorphism of coagulation factor XII (FXII) gene and the involvement of FXII activity (FXII:C) in patients with unexplained recurrent spontaneous abortion (URSA), and to elucidate its role in the pathogenesis of URSA. METHODS: This study included 203 patients with URSA (URSA group) and 171 healthy women with at least one child and no history of infertility or miscarriage (control group) in the southern area of Zhejiang Province. The C46T polymorphism of the FXII gene was analyzed with matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS) in all subjects. The values of prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, FXII:C and other coagulant parameters were determined. The frequency distribution of the wild-type (CC), heterozygote (CT), homozygote (TT) genotypes and C and T alleles were compared between the patients and controls. A comprehensive analysis of association was conducted between C46T genotypes and the FXII:C levels in URSA patients. RESULTS: The CC, CT, TT genotypes of the FXII gene were observed in 7 (3.4%, 7/203), 83 (40.9%, 83/203) and 113 (55.7%, 113/203) patients with URSA versus 7 (4.1%, 7/171), 46 (26.9%, 46/171) and 118 (69.0%, 118/171) controls. The frequency of CT in the patients with URSA was significantly higher than that in controls, but the frequency of TT in the patients was lower than that in controls (chi(2)=7.939, OR=1.884, 95%CI: 1.210-2.935, P<0.05). The frequencies of allele C and allele T were observed in 97 (23.9%, 97/406) and 309 (76.1%, 309/406) patients with URSA versus 60 (17.5%, 60/342) and 282 (82.5%, 282/342) controls. The distribution frequency of allele T in URSA group was lower than that in control group (chi(2)=4.510, OR=1.475, 95%CI: 1.029-2.115, P<0.05). The FXII: C levels in the patients were (102+/-13)% in CC genotype, (78+/-11)% in CT genotype and (59+/-9)% in TT genotype, respectively. The differences of the FXII: C levels between the CC and CT, CT and TT, CC and TT genotypes in the patients were significant (all P<0.05). CONCLUSIONS: The low level of FXII:C maybe result from the T allele of the FXII gene in URSA patients. The CT genotype might be relative to the pathogenesis of URSA in a Chinese Han female population from the southern area of Zhejiang province. PMID- 27561940 TI - [Meta-analysis of prognosis of ovarian preserving in young patients with early endometrial cancer]. AB - OBJECTIVE: To discuss the effect of preserving ovaries on the prognosis of young early endometrial cancer patients. METHODS: Searched English and Chinese databases by computors, including Cochrane library, Embase, PubMed, Web of Science, China National Knowledge Internet (CNKI), data base of Wanfang, China Science and Technology Journal (CSTJ) , and also relevant journals and magazines by hand. Retrieval time from January 1996 to March 2016. In accordance with the inclusion criteria, two independent investigators screened the studies and extracted the relevant data respectively. Then evaluated the quality of included studies. Finally, conducted the meta-analysis with RevMan 5.3 software from cochrane collaboration network, in which heterogeneity test of enrolled studies firstly was completed and combined analysis with effect models according to the heterogeneity secondary. In the light of the result, effect of remaining ovaries on the prognosis (5-year recurrence rate and 5-year overall survival rate) of young early endometrial cancer patients was determined. RESULTS: Ten trials were included. All of them were cohort studies, a total of 5 299 patients, in which 916 patients' ovaries were remained. Quality assessment of all 10 studies were based on Newcastle-Ottawa Scale (NOS) scale. All of the studies enrolled were of high quality with a score of >=7. After quality assessment,all studies illustrated the higher the quality. Meta-analysis showed that there was no statistically significant difference between who had ovarian preservation and without preservation in terms of 5-year overall survival rate [96.00% (863/899) vs 96.51% (3 736/3 871); RR=1.00, 95%CI: 0.99-1.02, P=0.792] and the 5-year recurrence rate [2.58% (7/271) vs 4.43% (51/1 150); RR=1.01, 95%CI: 0.46-2.22, P=0.986]. CONCLUSION: Ovarian preservation in young early stage patients of endometrial cancer could not effect the 5-year overall survival rateand the 5 year recurrence rate. PMID- 27561941 TI - [Study of coenzyme Q10 in the liver of preeclampsia pregnant rats]. AB - OBJECTIVE: To investigate the protective effect of coenzyme Q10 (CoQ10) in the liver of preeclampsiapregnant rats and the potential etiology. METHODS: Fifty pregnant SD rats were equally divided into the normal pregnant (NP) group (n=10) and the preeclampsia (PE) group (n=40) randomly. The PE rats (n=40) were equally divided into four groups randomly, distilled water (DW) group, CoQ10 group, CoQ10 combined magnesium(CM) group and magnesium (Mg) group were established by treating the preeclampsia rats on day 15 to 21 of gestation with different measures. As for all the 50 rats, systolic blood pressure (SBP) of rat tail was detected on day 10, 15 and 21 of gestation respectively, 24 hours proteinuria analysis were detected on day 10, 15 and 21 of gestation respectively, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in blood andsuperoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), caspase-3, Bcl-2 and Bax protein expression in liver tissue were detected by western blot assay on day 21 of gestation. RESULTS: (1) SBP and 24 hours proteinuria analysis: there was no statistic difference among all the five groups on day 10 of gestation (P>0.05). Whereas, SBP and 24 hours proteinuria analysis were significantly higher in CoQ10 group, CoQ10 combined CM group, CM group and DW group than that in NP group on day 15, 21 of gestation (P<0.05). And SBP and 24 hours proteinuria analysis were significantly lower in CoQ10 group, CoQ10 combined CM group and CM group than that in DW group on day 21 of gestation (P<0.05). (2) Liver function: among CoQ10 group, CoQ10 combined CM group, CM group, DW group and NP group, serum levels of ALT were respectively (52+/-7) , (34+/-9) , (49+/-10) , (70+/-19) , (30+/-7) U/L; and serum levels of AST were respectively (169+/-25) , (84+/-11) , (159+/-20) , (281+/-26) and (78+/-18) U/L. ALT and AST serum levels were significantly higher in CoQ10 group, CM group and DW group than that in NP group (P<0.05). ALT and AST serum levels were significant lower in CoQ10 combined CM group than those in CoQ10 group, CM group and DW group, respectively (P<0.05). ALT and AST serum levels were significant lower in CoQ10 group and CM group than that in DW group, respectively (P<0.05). (3) SOD, GSH-PX, MDA, caspase-3, Bcl-2 and Bax expression in liver tissue of rats: SOD expression was significant higher in CoQ10 group, CoQ10 combined CM group than thoes in CM group, DW group and NP group (P<0.05) ; SOD expression was significant lower in CM group, DW grouo than thoes in NP group (P<0.05) ; and SOD expression was significant higher in CM group than that in DW group (P<0.05) . Compared with CoQ10 group, CoQ10 combined CM group, CW group and DW group respectively, the GSH-PX and Bcl-2 protein expressions were significant higher in NP group (P<0.05) , while MDA, caspase-3 and Bax protein expressions were significant lower in NP group (P<0.05) ; compared with CoQ10 group, CoQ10 combined CM group and CW group respectively, the GSH-PX and Bcl-2 protein expressions were significant lower in DW group (P<0.05) , while MDA, caspase-3 and Bax protein expressions were significant higher in DW group (P<0.05) . CONCLUSIONS: Oxidative stress and apoptosis levles were upregulated in PE pregnant liver tissues. CoQ10 could effectively protect the liver by improving the liver functions and decreasing the apoptosis of liver cells in PE pregnant rats, and markedly decrease the oxidative stress and apoptosis in the livers. The protective roles of CoQ10 in liver might through its function of anti-oxidative stress and inhibiting cell apoptosis by regulating the balance of Bcl-2/Bax. PMID- 27561943 TI - A novel splinting technique to protect flaps of the posterior lower extremity. PMID- 27561942 TI - Human serum miR-34a as an indicator of exposure to ionizing radiation. AB - Radiation exposure in industrial accidents or nuclear device attacks is a major public health concern. There is an urgent need for markers that rapidly identify people exposed to ionizing radiation (IR). Finding a blood-based marker is advantageous because of the ease of sample collection. This study was designed to test the hypothesis that serum miR-34a could serve as an indicator of exposure to IR. Therefore, 44 women with breast cancer, where radiotherapy was part of their therapeutic protocol, were investigated in this study. After demonstrating the appropriateness of our microRNA (miRNA) extraction efficiency and miRNA assay in human serum, we analyzed the miR-34a level in paired serum samples before and after radiotherapy. Fifty Gy X-ray irradiation in daily dose fractions of 2 Gy, 5 days per week, was used in this study. We demonstrated that IR significantly increased serum level of miR-34a. By measuring miR-34a in serum, we could distinguish irradiated patients with sensitivity of 65 % and specificity of 75 %. According to this study, serum miR-34a has the potential to be used as an indicator of radiation exposure. PMID- 27561944 TI - Differential effect of exposure-based therapy and cognitive therapy on post traumatic stress disorder symptom clusters: A randomized controlled trial. AB - : A question remains regarding differential effects of exposure-based versus non exposure-based therapies on specific post-traumatic stress disorder (PTSD) symptom clusters. Traumatized emergency room patients were randomized to receive prolonged exposure (PE) or cognitive therapy (CT) without exposure. PE/CT had no differential effect on individual symptom clusters, and change in total PTSD score remained significant even after controlling for the reductions in all three symptom clusters. In addition, baseline levels of PTSD avoidance/intrusion/hyperarousal did not moderate the effects of PE and CT on total PTSD symptom scores. Taken together, these findings challenge the notion that PE and CT are specifically, and differentially, useful in treating one particular PTSD symptom cluster. PRACTITIONER POINTS: Despite their different theoretical backgrounds and techniques, the notion that PE and CT (without exposure) target different PTSD symptoms was not confirmed in this study. Thus, both interventions may in fact be equally effective for treating intrusion, avoidance and hyperarousal symptoms. Baseline levels of avoidance, intrusion and hyperarousal may not be good a priori indicators for PTSD treatment selection. The effect of PE and CT on PTSD as a whole does not seem to depend on a reduction in any specific symptom cluster. These findings indicate that exposure and non exposure interventions may lead to similar results in terms of reductions in specific PTSD symptoms. It is quite possible that individual PTSD clusters may respond to therapy in an inter-related fashion, with one cluster affecting the other. PMID- 27561945 TI - A multilevel analysis of lifestyle variations in symptoms of acute respiratory infection among young children under five in Nigeria. AB - BACKGROUND: Nigeria has the second highest estimated number of deaths due to acute respiratory infection (ARI) among children under five in the world. A common hypothesis is that the inequitable distribution of socioeconomic resources shapes individual lifestyles and health behaviors, which leads to poorer health, including symptoms of ARI. This study examined whether lifestyle factors are associated with ARI risk among Nigerian children aged less than 5 years, taking individual-level and contextual-level risk factors into consideration. METHODS: Data were obtained from the nationally representative 2013 Nigeria Demographic and Health Survey. A total of 28,596 surviving children aged 5 years or younger living in 896 communities were analyzed. We employed two-level multilevel logistic regressions to model the relationship between lifestyle factors and ARI symptoms. RESULTS: The multivariate results from multilevel regressions indicated that the odds of having ARI symptoms were increased by a number of lifestyle factors such as in-house biomass cooking (OR = 2.30; p < 0.01) and no hand washing (OR = 1.66; p < 0.001). An increased risk of ARI symptoms was also significantly associated with living in the North West region and the community with a high proportion of orphaned/vulnerable children (OR = 1.74; p < 0.001). CONCLUSIONS: Our findings underscore the importance of Nigerian children's lifestyle within the neighborhoods where they reside above their individual characteristics. Program-based strategies that are aimed at reducing ARI symptoms should consider policies that embrace making available basic housing standards, providing improved cooking stoves and enhancing healthy behaviors. PMID- 27561947 TI - Validity of short food questionnaire items to measure intake in children and adolescents: a systematic review. AB - BACKGROUND: Short food questions are appealing to measure dietary intakes. METHODS: A review of studies published between 2004 and 2016 was undertaken and these were included in the present study if they reported on a question or short item questionnaire (<=50 items, data presented as <=30 food groups) measuring food intake or food-related habits, in children (aged 6 months to 18 years), and reported question validity or reliability. Thirty studies met the inclusion criteria. RESULTS: Most questions assessed foods or food groups (n = 29), with the most commonly assessed being fruit (n = 22) or vegetable intake (n = 23), dairy foods and discretionary foods (n = 20 studies each). Four studies assessed food habits, with the most common being breakfast and meal frequency (n = 4 studies). Twenty studies assessed reliability, and 25 studies determined accuracy and were most commonly compared against food records. Evaluation of question performance relied on statistical tests such as correlation. CONCLUSIONS: The present study has identified valid and reliable questions for the range of key food groups of interest to public health nutrition. Questions were more likely to be reliable than accurate, and relatively few questions were both reliable and accurate. Gaps in repeatable and valid short food questions have been identified that will provide direction for future tool development. PMID- 27561946 TI - Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-alpha production by mononuclear phagocytes. AB - Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-alpha production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF alpha production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-alpha in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-alpha production by increasing levels of CLEC5A. PMID- 27561948 TI - Effects of intermittent pressure imitating rolling manipulation on calcium ion homeostasis in human skeletal muscle cells. AB - BACKGROUND: Homeostasis imbalance of intracellular Ca(2+) is one of the key pathophysiological factors in skeletal muscle injuries. Such imbalance can cause significant change in the metabolism of Ca(2+)-related biomarkers in skeletal muscle, such as superoxide dismutase (SOD), malondialdehyde (MDA) and creatine kinase (CK). Measurements of these biomarkers can be used to evaluate the degree of damage to human skeletal muscle cells (HSKMCs) injury. Rolling manipulation is the most popular myofascial release technique in Traditional Chinese Medicine. The mechanism of how this technique works in ameliorating muscle injury is unknown. This study aimed to investigate the possible Ca(2+) mediated effects of intermittent pressure imitating rolling manipulation (IPIRM) of Traditional Chinese Medicine in the injured HSKMCs. METHODS: The normal HSKMCs was used as control normal group (CNG), while the injured HSKMCs were further divided into five different groups: control injured group (CIG), Rolling manipulation group (RMG), Rolling manipulation-Verapamil group (RMVG), static pressure group (SPG) and static pressure-Verapamil group (SPVG). RMG and RMVG cells were cyclically exposed to 9.5-12.5 N/cm(2) of IPIRM at a frequency of 1.0 Hz for 10 min. SPG and SPVG were loaded to a continuous pressure of 12.5 N/cm(2) for 10 min. Verapamil, a calcium antagonist, was added into the culture mediums of both RMVG and SPVG groups to block the influx of calcium ion. RESULT: Compared with the CNG (normal cells), SOD activity was remarkably decreased while both MDA content and CK activity were significantly increased in the CIG (injured cells). When the injured cells were treated with the intermittent rolling manipulation pressure (RMG), the SOD activity was significantly increased and MDA content and CK activity were remarkably decreased. These effects were suppressed by adding the calcium antagonist Verapamil into the culture medium in RMVG. On the other hand, exposure to static pressure in SPG and SPVG affected neither the SOD activity nor the MDA content and CK activity in the injured muscle cells regardless of the presence of verapamil or not in the culture medium. CONCLUSION: These data suggest that the intermittent rolling pressure with the manipulation could ameliorate HSKMCs injury through a Ca(2+) dependent pathway. Static pressure did not lead to the same results. PMID- 27561949 TI - Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells. AB - Cancer stem cells are a subpopulation of cancer cells characterized by self renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients. PMID- 27561950 TI - Iridium(III)-Catalyzed Regioselective Intermolecular Unactivated Secondary Csp(3) -H Bond Amidation. AB - For the first time, a highly regioselective intermolecular sulfonylamidation unactivated secondary Csp(3) -H bond has been achieved using Ir(III) catalysts. The introduced N,N'-bichelating ligand plays a crucial role in enabling iridium nitrene insertion into a secondary Csp(3) -H bond via an outer-sphere pathway. Mechanistic studies and density functional theory (DFT) calculations demonstrated that a two-electron concerted nitrene insertion was involved in this Csp(3) -H amidation process. This method tolerates a broad range of linear and branched chain N-alkylamides, and provides efficient access to diverse gamma-sulfonamido substituted aliphatic amines. PMID- 27561951 TI - Dissemination and Implementation of Shared Decision Making Into Clinical Practice: A Research Agenda. AB - Shared decision making (SDM) is essential to advancing patient-centered care in emergency medicine. Despite many documented benefits of SDM, prior research has demonstrated persistently low levels of patient engagement by clinicians across many disciplines, including emergency medicine. An effective dissemination and implementation (D&I) framework could be used to alter the process of delivering care and to facilitate SDM in routine clinical emergency medicine practice. Here we outline a research and policy agenda to support the D&I strategy needed to integrate SDM into emergency care. PMID- 27561952 TI - The ideomotor recycling theory for language. AB - For language acquisition and processing, the ideomotor theory predicts that the comprehension and the production of language are functionally based on their expected perceptual effects (i.e., linguistic events). This anticipative mechanism is central for action-perception behaviors in human and nonhuman animals, but a recent ideomotor recycling theory has emphasized a language account throughout an evolutionary perspective. PMID- 27561953 TI - GPR55-dependent stimulation of insulin secretion from isolated mouse and human islets of Langerhans. AB - AIMS: The novel cannabinoid receptor GPR55 is expressed by rodent islets and it has been implicated in beta-cell function in response to a range of ligands. This study evaluated the effects of GPR55 ligands on intracellular calcium ([Ca2+ ]i ) levels and insulin secretion from islets isolated from GPR55 knockout (GPR55 -/- ) mice, age-matched wildtype (WT) mice and human pancreas. MATERIALS AND METHODS: GPR55 expression was determined by Western blotting and fluorescent immunohistochemistry. Changes in [Ca2+ ]i were measured by Fura-2 microfluorimetry. Dynamic insulin secretion was quantified by radioimmunoassay following perifusion of isolated islets. RhoA activity was monitored using a Rho binding domain pull down assay. RESULTS: Western blotting indicated that MIN6 beta-cells, mouse and human islets express GPR55 and its localization on human beta-cells was demonstrated by fluorescent immunohistochemistry. The pharmacological GPR55 agonist O-1602 (10 MUM) significantly stimulated [Ca2+ ]i and insulin secretion from WT mouse islets and these stimulatory effects were abolished in islets isolated from GPR55 -/- mice. In contrast, while the putative endogenous GPR55 agonist lysophosphatidylinositol (LPI, 5 uM) and the GPR55 antagonist cannabidiol (CBD, 1 uM) also elevated [Ca2+ ]i and insulin secretion, these effects were sustained in islets from GPR55 -/- mice. Stimulatory effects of O-1602 on [Ca2+ ]i and insulin secretion were also observed in experiments using human islets, but O-1602 did not activate RhoA in MIN6 beta-cells. CONCLUSIONS: Our results therefore suggest that GPR55 plays an important role in the regulation of mouse and human islet physiology, but LPI and CBD exert stimulatory effects on islet function by a GPR55-independent pathway(s). PMID- 27561956 TI - Patient Selection and Timing of Continuous Renal Replacement Therapy. AB - When and in whom to initiate continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) remains a highly controversial topic with large practice variation around the world. Even within countries, practice variation exists and recommendations for clinical practice are not specific. In this article, we report the consensus recommendations for timing and patient selection for CRRT - the results of the 2016 Acute Disease Quality Initiative XVII conference on 'precision CRRT'. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for use of CRRT in patients with AKI. Finally, we identify and highlight the areas of ongoing uncertainty and propose an agenda for future research. PMID- 27561955 TI - [Abdominal re-operations: Prevalence in elective and emergency surgery]. AB - BACKGROUND: The word "re-laparotomy" defines the surgical procedure in which the abdominal cavity is re-explored to resolve the complications of the disease or initial surgery. OBJECTIVE: To determine the prevalence of abdominal re operations in patients undergoing elective and emergency surgery in the General Hospital of Matamoros. MATERIAL AND METHODS: A retrospective, observational, longitudinal study was conducted by reviewing the medical records of patients with a re-operation from January 2014 to January 2015, statistically analysing the variables: Age, sex, type of surgery, complications, and postoperative course. RESULTS: A total of 21 re-operated patients were found, the majority of whom were women (52.38%). The cases were more common in ages between 70 and 79 years old, in both sexes. Almost two-thirds (61.91%) of re-operations were after an emergency surgery. The residual abscess (23.8%) and evisceration (23.8%) were the most frequent indications for re-intervention. There were postoperative complications in 23.8%, with wound dehiscence (60%) being the most frequent. There was an 85.6% survival rate after the re-intervention. CONCLUSIONS: The study showed a low incidence of re-interventions and a low mortality. There is evidence of major occurrence of abdominal re-interventions in advanced ages, in female patients, and emergency surgery. PMID- 27561957 TI - Cultural evolution need not imply group selection. AB - Richerson et al. make a compelling case for cultural evolution. In focusing on cultural group selection, however, they neglect important individual-level accounts of cultural evolution. While scientific discourse typically links cultural evolution to group selection and genetic evolution to individual selection, this association is due to historical accident only. We thus call for more consideration of individual-level cultural evolution. PMID- 27561958 TI - Functional outcome of total knee arthroplasty in patients with haemophilia. AB - INTRODUCTION: Haemophilic arthropathy (HA) is a debilitating complication of haemophilia which leads to TKA in severe cases. AIM: We conducted a prospective study of the outcome of TKA in our haemophilia cohort to define the outcomes in this population and increase the cost effectiveness of the procedure in our developing country. METHODS: We reviewed patients with haemophilia who underwent TKA between April 2010 and April 2014. Patients with at least 6 months of follow up were included. Preoperative knee scores (KSS and WOMAC) and the scores of the quality of life were recorded. Radiographic indices were registered pre- and postoperatively. Any complications were recorded. The patients underwent TKA with medial parapatellar approach. We had a low threshold for quadriceps snip when exposure was difficult. As our routine we did not use suction drains postoperatively. RESULTS: We included 83 patients (all males, 103 knees). The mean age of the patients was 35.8 years. The mean follow-up period was 45.1 months. Three patients (3.6%) had factor inhibitors. Twenty patients (24.1%) underwent bilateral simultaneous TKA. The mean admission time was 13.87 days. We had two cases of wound infection and one case of haematoma. None of our patients needed transfusion. All knee scores were significantly improved (P < 0.000). CONCLUSION: Total knee replacement is an effective procedure in treatment of HA. Definition of standards of care for this procedure, which are tailored for resources of a developing country, can have major impact in improving outcomes while maximizing cost effectiveness of this surgery. PMID- 27561959 TI - Amyotrophic Lateral Sclerosis Incidence and Previous Prescriptions of Drugs for the Nervous System. AB - BACKGROUND: An increased frequency of psychotic disorders in amyotrophic lateral sclerosis (ALS) families compared to controls has been reported. Aim of our study was to assess the relationship between nervous system drugs prescriptions and subsequent onset of ALS in a large Italian population. METHODS: The study population consisted of all subjects over 15 years at the 2001 Italian census, resident in Turin since 1996 (n = 687,324), followed up for ALS occurrence from 2002 to 2014. Exposure to nervous system drugs was measured until 2012, or until 1 year before ALS onset. The association was estimated for ever and cumulative exposure, through Cox proportional Hazards models adjusted for sex, age, education, marital status and drug co-exposure. RESULTS: In the analysis for ever exposure, opioids were significantly inversely associated with ALS risk (hazard ratio (HR) 0.59; 95% CI 0.35-0.97), while antiepileptics (HR 1.35; 95% CI 0.92 2.00) showed a marginally significantly positive association. Examining cumulative exposure, the protective role of opioids associated with more than 4 prescriptions and the risk effect of antiepileptics for over 6 prescriptions was confirmed. CONCLUSIONS: The present study revealed associations of ALS onset with previous exposure to opioids, maybe through the activation of delta receptor and sigma receptors and antiepileptics, which are novel findings to our knowledge. PMID- 27561960 TI - Quantitative changes of melanoma-associated antigens as a biomarker for targeted therapy response. PMID- 27561963 TI - Head of radiology school to be re-appointed after complaints from royal college. PMID- 27561962 TI - Nitrogen regulation of the xyl genes of Pseudomonas putida mt-2 propagates into a significant effect of nitrate on m-xylene mineralization in soil. AB - The nitrogen species available in the growth medium are key factors determining expression of xyl genes for biodegradation of aromatic compounds by Pseudomonas putida. Nitrogen compounds are frequently amended to promote degradation at polluted sites, but it remains unknown how regulation observed in the test tube is propagated into actual catabolism of, e.g. m-xylene in soil, the natural habitat of this bacterium. To address this issue, we have developed a test-tube to-soil model system that exposes the end-effects of remediation practices influencing gene expression of P. putida mt-2. We found that NO3- compared with NH4+ had a stimulating effect on xyl gene expression in pure culture as well as in soil, and that this stimulation was translated into increased m-xylene mineralization in soil. Furthermore, expression analysis of the nitrogen regulated genes amtB and gdhA allowed us to monitor nitrogen sensing status in both experimental systems. Hence, for nitrogen sources, regulatory patterns that emerge in soil reflect those observed in liquid cultures. The current study shows how distinct regulatory traits can lead to discrete environmental consequences; and it underpins that attempts to improve bioremediation by nitrogen amendment should integrate knowledge on their effects on growth and on catabolic gene regulation under natural conditions. PMID- 27561964 TI - Contributions of family social structure to the development of ultrasociality in humans. AB - The evolution of ultrasociality in humans may have involved the evolutionarily significant mechanisms that govern family social structure in many animal species. Adverse effects of ultrasociality in humans may be mediated by maladaptive effects of modern civilization on family groups, as many of the effects on both families and societies are especially severe in dense populations made possible by agriculture. PMID- 27561967 TI - Body mass and immune function, but not bill coloration, predict dominance in female mallards. AB - Competition over indivisible resources is common and often costly. Therefore, selection should favor strategies, including efficient communication, that minimize unnecessary costs associated with such competition. For example, signaling enables competitors to avoid engaging in costly asymmetrical contests. Recently, bill coloration has been identified as an information-rich signal used by some birds to mediate aggressive interactions and we evaluated this possibility in female mallards Anas platyrhynchos. Specifically, we conducted two rounds of competitive interactions among groups of unfamiliar adult female ducks. By recording all aggressive behaviors exhibited by each individual, as well as the identity of attack recipients, we were able to assign dominance scores and evaluate links between numerous physiological, morphological, and experimental variables that we predicted would influence contest outcome and dominance. Contrary to our predictions, dominance was not linked to any aspect of bill coloration, access to dietary carotenoids during development, two of three measures of immune function, or ovarian follicle maturation. Instead, heavier birds were more dominant, as were those with reduced immune system responses to an experimentally administered external immunostimulant, phytohemagglutinin. These results suggest that visual signals are less useful during the establishment of dominance hierarchies within multi-individual scramble competitions, and that immune function is correlated with contest strategies in competitions for access to limited resources. PMID- 27561966 TI - Common dysregulated pathways in obese adipose tissue and atherosclerosis. AB - BACKGROUND: The metabolic syndrome is becoming increasingly prevalent in the general population that is at simultaneous risk for both type 2 diabetes and cardiovascular disease. The critical pathogenic mechanisms underlying these diseases are obesity-driven insulin resistance and atherosclerosis, respectively. To obtain a better understanding of molecular mechanisms involved in pathogenesis of the metabolic syndrome as a basis for future treatment strategies, studies considering both inherent risks, namely metabolic and cardiovascular, are needed. Hence, the aim of this study was to identify pathways commonly dysregulated in obese adipose tissue and atherosclerotic plaques. METHODS: We carried out a gene set enrichment analysis utilizing data from two microarray experiments with obese white adipose tissue and atherosclerotic aortae as well as respective controls using a combined insulin resistance-atherosclerosis mouse model. RESULTS: We identified 22 dysregulated pathways common to both tissues with p values below 0.05, and selected inflammatory response and oxidative phosphorylation pathways from the Hallmark gene set to conduct a deeper evaluation at the single gene level. This analysis provided evidence of a vast overlap in gene expression alterations in obese adipose tissue and atherosclerosis with Il7r, C3ar1, Tlr1, Rgs1 and Semad4d being the highest ranked genes for the inflammatory response pathway and Maob, Bckdha, Aldh6a1, Echs1 and Cox8a for the oxidative phosphorylation pathway. CONCLUSIONS: In conclusion, this study provides extensive evidence for common pathogenic pathways underlying obesity-driven insulin resistance and atherogenesis which could provide a basis for the development of novel strategies to simultaneously prevent type 2 diabetes and cardiovascular disease in patients with metabolic syndrome. PMID- 27561965 TI - The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis. AB - BACKGROUND: The intracellular bacteria Anaplasma phagocytophilum are emerging zoonotic pathogens affecting human and animal health, and a good model for the study of tick-host-pathogen interactions. This tick-borne pathogen is transmitted by Ixodes scapularis in the United States where it causes human granulocytic anaplasmosis. Tick midguts and salivary glands play a major role during tick feeding and development, and in pathogen acquisition, multiplication and transmission. Vertebrate host proteins are found in tick midguts after feeding and have been described in the salivary glands of fed and unfed ticks, suggesting a role for these proteins during tick feeding and development. Furthermore, recent results suggested the hypothesis that pathogen infection affects tick metabolic processes to modify host protein digestion and persistence in the tick with possible implications for tick physiology and pathogen life-cycle. METHODS: To address this hypothesis, herein we used I. scapularis female ticks fed on uninfected and A. phagocytophilum-infected sheep to characterize host protein content in midguts and salivary glands by proteomic analysis of tick tissues. RESULTS: The results evidenced a clear difference in the host protein content between tick midguts and salivary glands in response to infection suggesting that A. phagocytophilum selectively manipulates the levels of vertebrate host proteins in ticks in a tissue-specific manner to facilitate pathogen infection, multiplication and transmission while preserving tick feeding and development. The mechanisms by which A. phagocytophilum manipulates the levels of vertebrate host proteins are not known, but the results obtained here suggested that it might include the modification of proteolytic pathways. CONCLUSIONS: The results of this study provided evidence to support that A. phagocytophilum affect tick proteolytic pathways to selectively manipulate the levels of vertebrate host proteins in a tissue-specific manner to increase tick vector capacity. Investigating the biological relevance of host proteins in tick biology and pathogen infection and the mechanisms used by A. phagocytophilum to manipulate host protein content is essential to advance our knowledge of tick-host-pathogen molecular interactions. These results have implications for the identification of new targets for the development of vaccines for the control of tick-borne diseases. PMID- 27561968 TI - Pentafluorobenzyl bromide-A versatile derivatization agent in chromatography and mass spectrometry: I. Analysis of inorganic anions and organophosphates. AB - Pentafluorobenzyl bromide (PFB-Br) is a versatile derivatization agent. It is widely used in chromatography and mass spectrometry since several decades. The bromide atom is largely the single leaving group of PFB-Br. It is substituted by wide a spectrum of nucleophiles in aqueous and non-aqueous systems to form electrically neutral, in most organic solvents soluble, generally thermally stable, volatile, strongly electron-capturing and ultraviolet light-absorbing derivatives. Because of these greatly favoured physicochemical properties, PFB-Br emerged an ideal derivatization agent for highly sensitive analysis of endogenous and exogenous substances including various inorganic and organic anions by electron capture detection or after electron-capture negative-ion chemical ionization in GC-MS. The present article attempts an appraisal of the utility of PFB-Br in analytical chemistry. It reviews and discusses papers dealing with the use of PFB-Br as the derivatization reagent in the qualitative and quantitative analysis of endogenous and exogenous inorganic anions in various biological samples, notably plasma, urine and saliva. These analytes include nitrite, nitrate, cyanide and dialkyl organophosphates. Special emphasis is given to mass spectrometry-based approaches and stable-isotope dilution techniques. PMID- 27561969 TI - Neural constraints and flexibility in language processing. AB - Humans process language with their neurons. Memory in neurons is supported by neural firing and by short- and long-term synaptic weight change; the emergent behaviour of neurons, synchronous firing, and cell assembly dynamics is also a form of memory. As the language signal moves to later stages, it is processed with different mechanisms that are slower but more persistent. PMID- 27561970 TI - Targeting blood-brain-barrier transcytosis - perspectives for drug delivery. AB - Efficient transcytosis across the blood-brain-barrier (BBB) is an important strategy for accessing drug targets within the central nervous system (CNS). Despite extensive research the number of studies reporting successful delivery of macromolecules or macromolecular complexes to the CNS has remained very low. In order to expand current research it is important to know which receptors are selective and abundant on the BBB so that novel CNS-targeting antibodies or other ligands could be developed, targeting those receptors for transcytosis. To do that, we have set up a proteomics- and transcriptomics-based workflow within the COMPACT project (Collaboration on the Optimization of Macromolecular Pharmaceutical Access to Cellular Targets) of the Innovative Medicines Initiative (IMI) of the EU. Here we summarise our overall strategy in endothelial transcytosis research, describe in detail the related challenges, and discuss future perspectives of these studies. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders". PMID- 27561971 TI - Ca2+-permeable AMPA receptor: A new perspective on amyloid-beta mediated pathophysiology of Alzheimer's disease. AB - alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the primary conduits of excitatory synaptic transmission. AMPARs are predominantly Ca2+-impermeable in the matured excitatory synapse, except under certain circumstances. Growing evidence implicates the Ca2+ permeability of AMPARs in the regulation of long-term synaptic plasticity and in the pathophysiology of several neurological disorders. Therefore, the Ca2+ conductance of AMPARs may have both physiological and pathological roles at synapses. However, our understanding of the role of Ca2+ permeable AMPARs (CP AMPARs) in Alzheimer's disease is limited. Here we discuss insights into the potential CP-AMPAR mediated pathophysiology of Alzheimer's disease, including: 1. Ca2+-mediated aberrant regulation of synapse weakening mechanisms, and 2. neuronal network dysfunction in the brain. Consideration of CP-AMPARs as primary drivers of pathophysiology could help in understanding synaptopathologies, and highlights the potential of CP-AMPARs as therapeutic targets in Alzheimer's disease. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 27561954 TI - Population-based cohort study of outcomes following cholecystectomy for benign gallbladder diseases. AB - BACKGROUND: The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all-cause 30-day readmissions and complications in a prospective population-based cohort. METHODS: Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all-cause 30-day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two level hierarchical structure with patients (level 1) nested within hospitals (level 2). RESULTS: Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16.3 per cent) were performed as an emergency, 4165 (46.8 per cent) as elective operations, and 3293 patients (37.0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7.1 per cent (633 of 8909) and 10.8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. CONCLUSION: Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics. PMID- 27561972 TI - Role of glutamatergic neurotransmission in the enteric nervous system and brain gut axis in health and disease. AB - Several studies have been carried out in the last 30 years in the attempt to clarify the possible role of glutamate as a neurotransmitter/neuromodulator in the gastrointestinal tract. Such effort has provided immunohistochemical, biomolecular and functional data suggesting that the entire glutamatergic neurotransmitter machinery is present in the complex circuitries of the enteric nervous system (ENS), which participates to the local coordination of gastrointestinal functions. Glutamate is also involved in the regulation of the brain-gut axis, a bi-directional connection pathway between the central nervous system (CNS) and the gut. The neurotransmitter contributes to convey information, via afferent fibers, from the gut to the brain, and to send appropriate signals, via efferent fibers, from the brain to control gut secretion and motility. In analogy with the CNS, an increasing number of studies suggest that dysregulation of the enteric glutamatergic neurotransmitter machinery may lead to gastrointestinal dysfunctions. On the whole, this research field has opened the possibility to find new potential targets for development of drugs for the treatment of gastrointestinal diseases. The present review analyzes the more recent literature on enteric glutamatergic neurotransmission both in physiological and pathological conditions, such as gastroesophageal reflux, gastric acid hypersecretory diseases, inflammatory bowel disease, irritable bowel syndrome and intestinal ischemia/reperfusion injury. PMID- 27561973 TI - [Treatment of bilateral spontaneous pneumothorax during pazopanib therapy for pulmonary soft tissue sarcoma metastases. What to do when there is so few evidence?] AB - Soft tissue sarcomas are rare malignant tumors with a great variety of histological types and different response to multimodality treatment. Pazopanib has been recently introduced for the treatment of non-adipocytic metastatic soft tissue sarcomas which are resistant to conventional chemotherapy. Spontaneous pneumothorax is a rare but well recognized complication of this molecule and its treatment is quite challenging. The case reported herein describes the surgical management of a simultaneous bilateral spontaneous pneumothorax in a patient with pulmonary metastases treated with pazopanib. It underlines the fact that the main objective should be the maintenance of the treatment in patients who benefit from it. Close oncologic and surgical collaboration is crucial in order to deal with adverse effects due to the anti-angiogenic action of pazopanib. PMID- 27561975 TI - [Diagnostic means for tuberculosis]. AB - Tuberculosis is a public health problem. In recent years, there is a change in the epidemiological profile of tuberculosis. The diagnosis of tuberculosis is based on clinical and radiological arguments but confirmation is bacteriological and/or histological. Culture remains the gold standard. Technological progress especially in molecular biology provides the clinician now new means of tuberculosis diagnostics. PMID- 27561974 TI - [Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. AB - INTRODUCTION: Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated. OBSERVATION: We report here the case of an unexpected good response after pembrolizumab failure obtained with paclitaxel in a 68-year-old patient with stage IV lung adenocarcinoma. Moreover, the response duration with paclitaxel was more than fourteen months. CONCLUSION: Our case suggests a mutual potentiation of chemotherapy and immunotherapy, and raises the issue of the treatment sequence to favor. PMID- 27561976 TI - [How to differentiate a thymic hyperplasia from an anterior mediastinal tumor?] PMID- 27561977 TI - [Pulmonary embolism revealing systemic lupus erythematosus in immunocompetent 56 years old man]. PMID- 27561978 TI - [About an unusual case of lipoid pneumonia]. AB - Lipoid pneumonia, although uncommon, should be considered when patients had a chronic pneumonia. We report a case of a 40-year-old female who presented with a chronic pneumonia. The CT-scan analysis, then the bronchoalveolar lavage, revealed a lipoid pneumonia. This lipoid pneumonia was caused by chronic inhalation of niaoulis vapors. This etiology has not been described in the literature. Alveolar condensation disappeared one month after bronchoalveolar lavage. This suggests that bronchoalveolar lavage may contribute to opacity regression besides exogenous lipid eviction. PMID- 27561979 TI - Population health and nurse education - time to step-up. PMID- 27561980 TI - Impact of parity on the efficiency of ovulation synchronization protocols in Holstein cows. AB - The objective of this study was to elucidate the impact of parity on the efficiency of three different protocols to synchronize time of ovulation in Holstein cows. All cows enrolled in this trial were categorized into primiparous and multiparous (M1 = 2-3 and M2 >=3 parities). Conception (P/AI at Day 28) and pregnancy (P/AI at Day 75) rates in the Presynch and CIDRsynch (31.7% and 35.5%; 26.3% and 28.4%, respectively) groups were significantly greater than that in spontaneous estrus (SE; 24.7 and 20.4%, respectively) group (P = 0.048 and 0.024; 0.041 and 0.011, respectively); however, no significant differences were detected between the SE and Ovsynch group for conception, pregnancy, and embryonic loss rates. Conception and pregnancy rates in the Presynch group decreased from 37.8% and 33.5%, respectively in primiparous cows to 29.6% and 23.1%, respectively in M1 cows (P = 0.022 and 0.007, respectively). However, conception and pregnancy rates using the CIDRsynch regimen were increased from 31.1% and 23.8% in primiparous cows to 41.4% and 34.7% in M1 cows (P = 0.017 and 0.008, respectively), and 40.9% and 33.6% in M2 cows (P = 0.021 and 0.019, respectively). Embryonic loss rate using the CIDRsynch protocol was decreased from 22.9% in primiparous cows to 15.1% and 18.2% in M1 and M2 cows (P = 0.013 and 0.130, respectively). On the contrary, embryonic loss rate using the Ovsynch protocol was increased from 11.5% in primiparous cows to 22.1% and 21.8% in M1 and M2 cows (P = 0.001 and 0.003, respectively). The Cox proportional-hazards model of embryonic loss showed significant associations for parity and season of calving with the hazard of embryonic loss (P = 0.001 and 0.016, respectively). Multiparous cows (M1 and M2) had a higher risk of embryonic loss than primiparous cows (Hazard ratio = 1.32 and 1.89, respectively). Our results indicate that use of the CIDRsynch regimen may achieve satisfactory conception and pregnancy rates in multiparous Holstein cows. However, synchronizing time of ovulation in primiparous cows with use of the Presynch treatment increases the fertility indices. PMID- 27561981 TI - Etonogestrel-Releasing Contraceptive Implant for Postpartum Adolescents: A Randomized Controlled Trial. AB - STUDY OBJECTIVE: To compare immediate postpartum insertion of the contraceptive implant to placement at the 6-week postpartum visit among adolescent and young women. DESIGN: Non-blinded, randomized controlled trial. SETTING AND PARTICIPANTS: Postpartum adolescents and young women ages 14-24 years who delivered at an academic tertiary care hospital serving rural and urban populations in North Carolina. INTERVENTIONS: Placement of an etonogestrel releasing contraceptive implant before leaving the hospital postpartum, or at the 4-6 week postpartum visit. MAIN OUTCOME MEASURES: Contraceptive implant use at 12 months postpartum. RESULTS: Ninety-six participants were randomized into the trial. Data regarding use at 12 months were available for 64 participants, 37 in the immediate group and 27 in the 6-week group. There was no difference in use at 12 months between the immediate group and the 6-week group (30 of 37, 81% vs 21 of 27, 78%; P = .75). At 3 months, the immediate group was more likely to have the implant in place (34 of 37, 92% vs 19 of 27, 70%; P = .02). CONCLUSION: Placing the contraceptive implant in the immediate postpartum period results in a higher rate of use at 3 months postpartum and appears to have similar use rates at 12 months compared with 6-week postpartum placement. Providing contraceptive implants to adolescents before hospital discharge takes advantage of access to care, increases the likelihood of effective contraception in the early postpartum period, appears to have no adverse effects on breastfeeding, and might lead to increased utilization at 1 year postpartum. PMID- 27561982 TI - Food and Drug Administration approval of sustained-release buprenorphine for treatment of opioid dependence: realizing its potential. PMID- 27561983 TI - Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation. AB - 8,9-Dihydro-2,4,7,9a-tetraazabenzo[cd]azulen-6(7H)-ones were designed and synthesized as a new class of PARP-1/2 inhibitors. The compounds displayed a variable pattern of PARP-1/2 enzymes inhibition profile that, in part, paralleled the antiproliferative activity in cell lines. Among them, compound 9e exhibited not only the significant IC50 value of 28nM in the PARP-1 and 7.7nM in PARP-2 enzyme assay, but also a profound synergic efficacy combined with temozolomide with PF50 values of 2.6, 2.5, and 6.5 against MDA-MB-468, SW-620 and A549 and cell line, respectively. PMID- 27561984 TI - Toward chelerythrine optimization: Analogues designed by molecular simplification exhibit selective growth inhibition in non-small-cell lung cancer cells. AB - A series of novel chelerythrine analogues was designed and synthesized. Antitumor activity was evaluated against A549, NCI-H1299, NCI-H292, and NCI-H460 non-small cell lung cancer (NSCLC) cell lines in vitro. The selectivity of the most active analogues and chelerythrine was also evaluated, and we compared their cytotoxicity in NSCLC cells and non-tumorigenic cell lines, including human umbilical vein endothelial cells (HUVECs) and LL24 human lung fibroblasts. In silico studies were performed to establish structure-activity relationships between chelerythrine and the analogues. The results showed that analogue compound 3f induced significant dose-dependent G0/G1 cell cycle arrest in A549 and NCI-H1299 cells. Theoretical studies indicated that the molecular arrangement and electron characteristics of compound 3f were closely related to the profile of chelerythrine, supporting its activity. The present study presents a new and simplified chelerythrinoid scaffold with enhanced selectivity against NSCLC tumor cells for further optimization. PMID- 27561986 TI - Dimensionality of Helicopter Parenting and Relations to Emotional, Decision Making, and Academic Functioning in Emerging Adults. AB - The current study tests the underlying structure of a multidimensional construct of helicopter parenting (HP), assesses reliability of the construct, replicates past relations of HP to poor emotional functioning, and expands the literature to investigate links of HP to emerging adults' decision-making and academic functioning. A sample of 377 emerging adults (66% female; ages 17-30; 88% European American) were administered several items assessing HP as well as measures of other parenting behaviors, depression, anxiety, decision-making style, grade point average, and academic functioning. Exploratory factor analysis results suggested a four-factor, 23-item measure that encompassed varying levels of parental involvement in the personal and professional lives of their children. A bifactor model was also fit to the data and suggested the presence of a reliable overarching HP factor in addition to three reliable subfactors. The fourth subfactor was not reliable and item variances were subsumed by the general HP factor. HP was found to be distinct from, but correlated in expected ways with, other reports of parenting behavior. HP was also associated with poorer functioning in emotional functioning, decision making, and academic functioning. Parents' information-seeking behaviors, when done in absences of other HP behaviors, were associated with better decision making and academic functioning. PMID- 27561985 TI - MicroRNA-21 regulates prostaglandin E2 signaling pathway by targeting 15 hydroxyprostaglandin dehydrogenase in tongue squamous cell carcinoma. AB - BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive forms of head and neck/oral cancer (HNOC), and is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. Identifying the deregulation of microRNA-mRNA regulatory modules (MRMs) is crucial for understanding the role of microRNA in OTSCC. METHODS: A comprehensive bioinformatics analysis was performed to identify MRMs in HNOC by examining the correlation among differentially expressed microRNA and mRNA profiling datasets and integrating with 12 different sequence-based microRNA target prediction algorithms. Confirmation experiments were performed to further assess the correlation among MRMs using OTSCC patient samples and HNOC cell lines. Functional analyses were performed to validate one of the identified MRMs: miR-21 15-Hydroxyprostaglandin Dehydrogenase (HPGD) regulatory module. RESULTS: Our bioinformatics analysis revealed 53 MRMs that are deregulated in HNOC. Four high confidence MRMs were further defined by confirmation experiments using OTSCC patient samples and HNOC cell lines, including miR-21-HPGD regulatory module. HPGD is a known anti-tumorigenic effecter, and it regulates the tumorigenic actions of Prostaglandin E2 (PGE2) by converts PGE2 to its biologically inactive metabolite. Ectopic transfection of miR-21 reduced the expression of HPGD in OTSCC cell lines, and the direct targeting of the miR-21 to the HPGD mRNA was confirmed using a luciferase reporter gene assay. The PGE2-mediated upregulation of miR-21 was also confirmed which suggested the existence of a positive feed forward loop that involves miR-21, HPGD and PGE2 in OTSCC cells that contribute to tumorigenesis. CONCLUSIONS: We identified a number of high-confidence MRMs in OTSCC, including miR-21-HPGD regulatory module, which may play an important role in the miR-21-HPGD-PGE2 feed-forward loop that contributes to tumorigenesis. PMID- 27561987 TI - [Different types of injection in temporomandibular disorders (TMD) treatment]. AB - INTRODUCTION: Intramuscular injections of botulinum toxin of type A (BoNTA) can release tension from masticatory and cervical muscles. Intra-articular injections relieve pain and sometimes diminish joint clicking and locking that occur during mouth opening. METHODS: Intramuscular injection of BoNTA is performed in our department since 2002. Injected muscles are masseter and temporal muscles. Later on, intra-articular injections of sodium hyaluronate were added, followed on a later stage by intra-articular injections of BoNTA for patients presenting with pain higher than 5/10 on an analogic visual scale. RESULTS: Eighty-five percent of the patients treated with intramuscular BoNTA injection improved. Total or partial pain relief was obtained in 95 % of the patients after intra-articular sodium hyaluronate injections. Seventy-six percent of the 56 patients treated by mean of intra-articular BoNTA injections improved, sometimes with a complete pain relief. DISCUSSION: These different techniques allow for good results, even if they do not represent a revolution in the treatment of temporomandibular disorders. In the hands of experienced practitioners, they have a low morbidity, are well accepted and are cost-effective. PMID- 27561988 TI - [A well-articulated Congress 2016]. PMID- 27561989 TI - Hierarchical effects on target detection and conflict monitoring. AB - Previous neuroimaging studies have demonstrated a hierarchical functional structure of the frontal cortices of the human brain, but the temporal course and the electrophysiological signature of the hierarchical representation remains unaddressed. In the present study, twenty-one volunteers were asked to perform a nested cue-target task, while their scalp potentials were recorded. The results showed that: (1) in comparison with the lower-level hierarchical targets, the higher-level targets elicited a larger N2 component (220-350 ms) at the frontal sites, and a smaller P3 component (350-500 ms) across the frontal and parietal sites; (2) conflict-related negativity (non-target minus target) was greater for the lower-level hierarchy than the higher-level, reflecting a more intensive process of conflict monitoring at the final step of target detection. These results imply that decision making, context updating, and conflict monitoring differ among different hierarchical levels of abstraction. PMID- 27561991 TI - CIK immunotherapy in refractory hematologic malignancies. PMID- 27561990 TI - Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke. AB - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complications after thrombolysis. METHODS: A total of 189 ischemic stroke patients were prospectively enrolled. Blood samples for leukocyte, neutrophil, and lymphocyte counts were obtained at admission and at 3-6, 12-18, and 36-48 h after IVT. Head CT was performed on admission and repeated after 36-48 h, and a CT scan was done immediately in case of clinical worsening. Hemorrhagic events were categorized as symptomatic intracranial hemorrhage (sICH) and parenchymal hematomas (PH) according to previously published criteria. RESULTS: An increasing trend in the NLR was observed after stroke, and the NLR was higher in patients who developed PH or sICH at 3-6, 12-18, and 36-48 h after IVT (P < 0.01) than in those without PH or sICH. The optimal cutoff value for the serum NLR as an indicator for auxiliary diagnosis of PH and sICH was 10.59 at 12-18 h. Furthermore, the NLR obtained at 12-18-h post-treatment was independently associated with PH (adjusted odds ratio [OR] 1.14) and sICH (adjusted OR 1.14). In addition, patients with a NLR >=10.59 had an 8.50-fold greater risk for PH (95 % confidence interval [CI] 2.69-26.89) and a 7.93-fold greater risk for sICH (95 % CI 2.25-27.99) than patients with a NLR <10.59. CONCLUSIONS: NLR is a dynamic variable, and its variation is associated with HT after thrombolysis in stroke patients. PMID- 27561992 TI - Five novel species in the Lodderomyces clade associated with insects. AB - During a survey of yeasts associated with insects in Central China's natural ecosystems, 116 yeast strains were isolated from the gut of adult insects in two families and from one beetle larva. Among the yeasts isolated in this study, 102 strains were identified as 20 known species in the class Saccharomycetes. The remaining 14 strains were identified as representing five novel species in the Lodderomyces clade based on the combined sequences of the D1/D2 domains of the LSU rRNA gene and the internal transcribed spacer (ITS) regions, as well as other taxonomic characteristics. Lodderomyces beijingensis sp. nov. (type strain CBS 14171T=CICC 33087T=NYNU 15764T) formed a clade with Lodderomyces elongisporus and Candida oxycetoniae. The other four novel species, namely Candida margitis sp. nov. (type strain CBS 14175T=CICC 33091T=NYNU 15857T), Candida xiaguanensis sp. nov. (type strain CBS 13923T=CICC 33056T=NYNU 1488T), Candida parachauliodis sp. nov. (type strain CBS 13928T=CICC 33058T=NYNU 14959T) and Candida coleopterorum sp. nov. (type strain CBS 14180T=CICC 33084T=NYNU 1582T), showed close relationships to the species near Candida parapsilosis, Candida sakaeoensis, Candida chauliodes and Candida corydalis. Descriptions of these novel yeast species are provided as well as discussions of their ecology in relation to their insect hosts. PMID- 27561993 TI - Patient experiences with family medicine: a longitudinal study after the Dutch health care reforms in 2006. AB - BACKGROUND: In 2006 The Dutch Health Care system changed to a market oriented system. The GP remuneration changed from +/- 2/3 capitation patients and 1/3 private patients before 2006 to a mixed payment scheme. From 2006 onward every patient was insured and the GP received partly capitation, partly fees for consultations and for specific services. This change coincided with many other organisational changes in General Practice care. Our research question was if during the years after 2006 patient experiences of Dutch family practice had changed. We also wanted to explore the influence of patient and practice characteristics on patient experiences. Data on patient experiences were available from 2007 to 2012. METHOD: In a series of annual cross sectional patient surveys the performance of GPs and practices was measured. Patient sampling took place as a part of the Dutch accreditation program in 1657 practices involving 2966 GPs. Patients' experiences, gender, age, health status, and number of annual consultations were documented as well as the type and location of practices. Linear regression analysis was used to examine time trends in patient experiences and the impact of patient and practice characteristics. RESULTS: 78,985 patients assessed the performance of 2966 GPs, and 45,773 patients assessed the organisation of 1657 practices. The number of patients with positive experiences increased significantly between 2007 and 2012; respectively 4.8 % for GPs (beta 0.20 and p < 0.0001) and 6.6 % for practices (beta 0.10, p < 0.004). Higher age, having no chronic illness, more frequent consultations and attending single-handed practices, predicted better patient experiences. CONCLUSIONS: In our evaluation of patient experiences with general practice care from 2007 to 2012 we found an increase of 4.8 % for GPs and 6.6 % for practices respectively. This improvement is significant. While no direct causation can be made, possible explanations may be found in the various reforms in Dutch family practice since 2006. More insight is needed into key determinants of this improvement before policymakers and care providers can attribute the improvement to these reforms. PMID- 27561995 TI - The role of cultural group selection in explaining human cooperation is a hard case to prove. AB - We believe cultural group selection is an elegant theoretical framework to study the evolution of complex human behaviours, including large-scale cooperation. However, the empirical evidence on key theoretical issues - such as levels of within- and between-group variation and effects of intergroup competition - is so far patchy, with no clear case where all the relevant assumptions and predictions of cultural group selection are met, to the exclusion of other explanations. PMID- 27561994 TI - Electric pulses: a flexible tool to manipulate cytosolic calcium concentrations and generate spontaneous-like calcium oscillations in mesenchymal stem cells. AB - Human adipose mesenchymal stem cells (haMSCs) are multipotent adult stem cells of great interest in regenerative medicine or oncology. They present spontaneous calcium oscillations related to cell cycle progression or differentiation but the correlation between these events is still unclear. Indeed, it is difficult to mimic haMSCs spontaneous calcium oscillations with chemical means. Pulsed electric fields (PEFs) can permeabilise plasma and/or organelles membranes depending on the applied pulses and therefore generate cytosolic calcium peaks by recruiting calcium from the external medium or from internal stores. We show that it is possible to mimic haMSCs spontaneous calcium oscillations (same amplitude, duration and shape) using 100 MUs PEFs or 10 ns PEFs. We propose a model that explains the experimental situations reported. PEFs can therefore be a flexible tool to manipulate cytosolic calcium concentrations. This tool, that can be switched on and off instantaneously, contrary to chemicals agents, can be very useful to investigate the role of calcium oscillations in cell physiology and/or to manipulate cell fate. PMID- 27561996 TI - On-Resonance Fluorescence, Resonance Rayleigh Scattering, and Ratiometric Resonance Synchronous Spectroscopy of Molecular- and Quantum Dot-Fluorophores. AB - Existing studies on molecular fluorescence have almost exclusively been focused on Stokes-shifted fluorescence spectroscopy (SSF) in which the emitted photon is detected at the wavelengths longer than that for the excitation photons. Information on fluorophore on-resonance fluorescence (ORF) and resonance Rayleigh scattering (RRS) is limited and often problematic due to the complex interplay of the fluorophore photon absorption, ORF emission, RRS, and solvent Rayleigh scattering. Reported herein is a relatively large-scale systematic study on fluorophore ORF and RRS using the conventional UV-vis extinction and SSF measurements in combination with the recently reported ratiometric resonance synchronous spectroscopic (R2S2, pronounced as "R-Two-S-Two") method. A series of fundamental parameters including fluorophore ORF cross sections and quantum yields have been quantified for the first time for a total of 12 molecular and 6 semiconductor quantum dot (QD) fluorophores. All fluorophore spectra comprise a well-defined Gaussian peak with a full width at half-maximum ranging from 4 to 30 nm. However, the RRS features of fluorophores differ drastically. The effect of fluorophore aggregation on its RRS, UV-vis, R2S2, and SSF spectra was also discussed. This work highlights the critical importance of the combined UV-vis extinction, SSF, and R2S2 spectroscopic measurements for material characterizations. The method and insights described in this work can be directly used for improving the reliability of RRS spectroscopic methods in chemical analysis. In addition, it should pave the way for developing novel R2S2-based analytical applications. PMID- 27561997 TI - Mothers' perinatal and infant mental health knowledge in a Johannesburg township setting. AB - OBJECTIVE: This paper examines maternal knowledge regarding perinatal and infant mental health amongst mothers in Alexandra township, Johannesburg. The applicability and utility of these Western-derived concepts in a low socio economic South African setting is examined. METHOD: A concurrent mixed methods approach was used. Descriptive statistical analysis was conducted on the responses of 255 mothers on a structured questionnaire, designed to elicit levels of knowledge about the relational needs and awareness of infants and the psychosocial needs of mothers, to determine trends in mothers' knowledge. A thematic content analysis was also conducted on the responses to determine themes and understandings within the mothers' responses. RESULTS: Maternal knowledge in Alexandra regarding perinatal and infant mental health correlates with maternal education levels. Cultural, contextual and psychological factors appear to influence maternal understandings of infant sentience and maternal ambivalence. CONCLUSIONS: Further research is required to determine possible contributions of the denial of negative maternal affect post-birth to elevated levels of post natal depression found amongst South African mothers parenting in adverse circumstances. There is a need for education regarding key messages from the neuroscience of development, to give these parents opportunities to raise their children in a way that supports healthy cognitive and emotional development. PMID- 27561998 TI - The Ububele Baby Mat intervention: facilitating meaning in a multi-cultural context. AB - This paper expands on the continuing understanding of the Ububele Baby Mat Project - a community-based parent-infant mental health intervention now offered at six primary healthcare clinics in Alexandra, Johannesburg. This paper describes the influence of cultural diversity and the complex layers of meaning making involved in the Baby Mat intervention. Meaning-making is a collaborative process between the caregiver-infant dyad's cultural beliefs and experiences, the Baby Mat couple's relationship, knowledge and skills, and the additional minds of the multicultural supervision group. This paper aims to clarify these three layers of co-constructed meaning-making involved in the Baby Mat intervention. Three central themes are thus presented to discuss the impact of multi-cultural, multi-racial and multi-lingual therapeutic dyads on the process of the Baby Mat intervention. These core themes are the verbal and non-verbal meanings of presenting problems brought by caregiver-infant dyads; the value and obstacles involved within a cross-cultural baby mat couple; and the significance of a reflective group supervision space. Case extracts are used to illustrate these processes of multiple minds at play during a Baby Mat session. PMID- 27561999 TI - Behaviour planning and problem solving deficiencies in children with symptoms of attention deficit hyperactivity disorder from the Balobedu culture, Limpopo province, South Africa. AB - OBJECTIVE: To compare planning behaviour (frontal lobe functioning) in children with and without symptoms of attention deficit hyperactivity disorder (ADHD). METHOD: A total of 90 children (45 with symptoms of ADHD and 45 matched controls without ADHD symptoms) of both genders, who were medication naive, from the Balobedu culture (Limpopo province, South Africa), aged 7-13 years, participated in the study. The performance of the two groups was compared on a test of planning and problem solving, the Tower of London (ToL) task. The results were analysed as a function of gender and ADHD subtype. The Finger Tapping test (testing fine motor skills) was used as a control test to verify that the expected differences were not due to poor motor skills. RESULTS: The children with ADHD symptoms scored significantly lower than the non-ADHD comparison group which indicated deficiency in frontal lobe functioning (p = 0.00). The difference in performance was not due to poor motor control (p = 0.70). CONCLUSION: Children with ADHD symptoms show deficits in behavioural planning which indicates impairment of functions of the frontal areas supplied by the mesocortical dopamine branch. More so than others, the ADHD Inattentive and Combined subtypes showed poor performance in the Tower of London task, indicating poor organisational and planning skills in these groups. The results also did show that the difference was not due to problems with motor control and that the ToL task is a culture-fair instrument for testing planning behaviour. PMID- 27562000 TI - Towards a comprehensive test specification for normative adolescent fears: a conservation of resources perspective. AB - OBJECTIVE: This study assessed the extent to which the primary tenets of Conservation of Resources theory provide an adequate basis for categorising and conceptualising normative adolescent fears. METHOD: Initial descriptive research, using data obtained from a sample of South African adolescents (n = 163), used systematic emergent content analysis to develop a test specification (i.e., content domains and manifestations of content domains) relevant to measures of normative adolescent fears, with subsequent a priori content analyses being used to explore the content validity of the test specification with respect to the item-content of selected normative childhood and adolescent fear schedules. RESULTS: Analyses suggest that content domains proposed by Conservation of Resources theory provide an adequate (exhaustive and mutually exclusive) basis for reliably conceptualising and categorising normative adolescent fears and for predicting the valence of specific adolescent fears. CONCLUSIONS: A Conservation of Resources perspective was found to be of heuristic value in exploring content domains relevant to normative adolescent fears, and would appear to hold promise as a useful conceptual framework for future research in the field. PMID- 27562002 TI - The role of fortitude in relation to exposure to violence among adolescents living in lower socio-economic areas in South Africa. AB - OBJECTIVE: There is compelling evidence that a significant proportion of adolescents exposed to violence do not develop trauma-related symptoms, but adapt successfully. This differential vulnerability has propelled research into identifying factors that promote coping. This study focused on the role of fortitude in the relationship between violence and trauma-related symptoms among South African adolescents living in two low-income communities. Fortitude is derived from positive cognitive appraisals of the self, the family and external sources of support. METHOD: Adolescents (n = 498) completed an adapted version of the Harvard Trauma Scale (HTS) and the Fortitude Questionnaire (FORQ). RESULTS: Moderated regression analysis demonstrated that fortitude had a health-sustaining and stress-buffering role. Adolescents who displayed high levels of fortitude had lower levels of trauma symptoms in relation to exposure to violence (stress buffering) and were able to maintain their levels of wellbeing irrespective of the nature and extent of such exposure (health-sustaining). CONCLUSION: The study provides evidence for fortitude as a protective factor by highlighting the role of specific cognitive appraisals related to fortitude in facilitating adaptation in relation to trauma. The study also underscores the relevance of using clinical interventions that target problematic cognitive appraisals and strengthen perceptions of coping. PMID- 27562001 TI - Tobacco and alcohol use among adolescents in South Africa: shared and unshared risks. AB - OBJECTIVE: Tobacco and alcohol use by adolescents are major public health concerns in South Africa. However, the extent to which key psychosocial risk factors for tobacco use and alcohol use by adolescents in South Africa are shared or unshared is unclear. This study sought to examine the shared and unshared risk factors for tobacco and alcohol use among adolescents in Johannesburg. METHOD: Participants comprised 736 males and females aged 12-17 years who were recruited via a household survey conducted during 2004. The participants were interviewed using a questionnaire comprising measures of personal, family (parental bonding and family legal drug use) and contextual (school and neighbourhood) factors. Separate multiple logistic regression analyses were conducted to predict lifetime alcohol use and lifetime tobacco use from variables within each domain (personal, family and contextual), controlling for demographic factors. RESULTS: Personal, family (parental bonding) and contextual factors (school factors) were primarily shared risk factors for tobacco and alcohol use, while family legal drug use and neighbourhood factors were largely unshared. CONCLUSIONS: Interventions addressing personal, parenting and schooling factors are likely to have an impact on preventing both tobacco and alcohol use, whereas interventions focused on ameliorating family drug use and neighbourhood factors may need to be more substance-specific. PMID- 27562003 TI - "Every time that month comes, I remember": using cognitive interviews to adapt grief measures for use with bereaved adolescents in South Africa. AB - OBJECTIVE: To assess standard grief measures through cognitive interviews with bereaved adolescents in Free State, South Africa, and make recommendations designed to improve the measurement of grief in this and similar populations. METHODS: Twenty-one parentally bereaved adolescents participated in semi structured cognitive interviews about the Core Bereavement Items (CBI) questionnaire, Grief Cognitions Questionnaire for Children (GCQ-C), or Intrusive Griefs Thoughts Scale (IGTS). RESULTS: Interviewees offered valuable insights for improving grief measurement with this population (e.g., consensus that not thinking frequently about a deceased loved one was shameful, aversion to terms including "died"). Participants were better able to apply response options denoting specific frequencies (e.g., "once or twice a week") versus general ones (e.g., "a little bit of the time"). Questions intended to gauge grief commonly elicited responses reflecting the impact of loss on adolescents' basic survival instead of psychological wellbeing. CONCLUSIONS: The need for psychological support is high among orphans and vulnerable children. Tools for measuring psychological outcomes can provide evidence of programme effects and guide decision making about investment. Grief measures used with adolescents in South Africa should account for the issues raised by cognitive interviewees in the study, including question and response option complexity, linguistic preferences, and cultural norms. PMID- 27562004 TI - Parental HIV/AIDS and psychological health of younger children in South Africa. AB - OBJECTIVE: We examined several indicators of psychological health in a sample of orphans and vulnerable children (OVC) to determine if there were significant differences between those orphaned by AIDS and those orphaned by other causes, and if there were gender differences. METHOD: Our sample consisted of 119 young children (ages 6-10 years) who participated in a non-governmental organisation (NGO)-supported social services programme in a low-resource, non-urban community in South Africa. We collected data on three groups: non-orphans (OVC1; n = 45); orphans due to AIDS (OVC2; n = 43); and other orphans (OVC3; n = 31). Parents of non-orphans and legal guardians of orphans rated their children on a 112-item, age appropriate Child Behaviour Checklist (CBCL), South Africa version. RESULTS: Children in the OVC2 group were significantly different from their peers on Internalising Problems and Somatic Complaints, while OVC3 group had a higher proportion of children in the at-risk range on Social Problems compared to OVC2. Females had elevated scores on the anxious/depressed, internalising problems, total problems, and sluggish cognitive tempo scales compared to males. There was an interaction between factors, such that boys in OVC2 had elevated mean scores on Somatic Complaints. These findings suggest increased vulnerability for girls on emotional issues and for boys on somatic problems. PMID- 27562005 TI - Tech-savvy parenting: a guide to raising safe children in a digital world. PMID- 27562006 TI - The importance of the first 1 000 days of life. PMID- 27562007 TI - Dynamics of Heterocapsa sp. and the associated attached and free-living bacteria under the influence of dispersed and undispersed crude oil. AB - : While many studies have examined the impact of oil on phytoplankton or bacteria, very few considered the effects on the biological complex formed by phytoplankton and their associated phytoplankton-attached (PA) and free-living (FL) bacteria. However, associated bacteria can affect the physiology of phytoplankton and influence their stress responses. In this study, we monitored the growth of Heterocapsa sp., an armoured dinoflagellate, exposed to crude oil, Corexit dispersant, or both. Growth of Heterocapsa sp. is unaffected by crude oil up to 25 ppm, a concentration similar to the lower range measured on Florida beaches after the Deepwater Horizon oil spill. The PA bacteria community was resistant to exposure, whereas the FL community shifted towards oil degraders; both responses could contribute to Heterocapsa sp. oil resistance. The growth rate of Heterocapsa sp. decreased significantly only when exposed to dispersed oil at 25 ppm, indicating a synergistic effect of dispersant on oil toxicity in this organism. For the first time, we demonstrated the decoupling of the responses of the PA and FL bacteria communities after exposure to an environmental stress, in this case oil and dispersant. Our findings suggest new directions to explore in the understanding of interactions between unicellular eukaryotes and prokaryotes. SIGNIFICANCE AND IMPACT OF THE STUDY: In the environment, oil spills have the capacity to modify phytoplankton communities, with important consequences on the food web and the carbon cycle. We are just beginning to understand the oil resistance of phytoplankton species, making it difficult to predict community response. In this study we highlighted the strong resistance of Heterocapsa sp. to oil, which could be associated with its resilient attached bacteria and oil degradation by the free-living bacteria. This finding suggests new directions to explore in the understanding of oil impacts and interactions between eukaryotic and prokaryotic microbes. PMID- 27562008 TI - Gene-culture interaction and the evolution of the human sense of fairness. AB - How Darwinian evolution would produce creatures with the proclivity of Darwinian generosity, most of them voluntarily giving up the immediate benefit for themselves or their genes, remains a puzzle. This study targets a problem, the origin of human sense of fairness, and uses fairness-related genes and the social manipulation of Darwinian generosity as the key variables underlying the human sense of fairness, inequity aversion, as well as their relationships within cooperation, and the anticipation foresight of the way relationships are affected by resource division, given the assumption of randomly matched partners. Here we suggest a model in which phenotype will gradually converge towards the perfect sense of fairness along with the prospect of cooperation. Later, the sense of fairness will decrease but it is never extinct. Where social manipulation of Darwinian generosity overshadows genetics, the sense of fairness could be acute to the degree of social manipulation. Above all, there still exists a threshold in the degree of social manipulation, beyond which altruism dominates selfishness in human cooperation. Finally, we propose three new directions toward more realistic scenarios stimulated by recent development of the synergy between statistical physics, network science and evolutionary game theory. PMID- 27562009 TI - The day of reckoning: Does human ultrasociality continue? AB - To counter human ultrasociality, alternative communities can arise (ongoing), and, unlike insects, lower echelons can unite and rebel. Examples include movements such as: "Black Lives Matter," "Fight for $15," "Occupy," and the "Village Movement." To strengthen ultrasociality, a surplus bottom echelon can be reduced: for example, by means such as imprisoning Blacks, deporting immigrants, wars, and the Holocaust. Alternatively, a new structure could be created, for example, ISIL (even more ultrasocial?). PMID- 27562010 TI - The reification objection to bottom-up cognitive ontology revision. AB - Anderson (2014) proposes a bottom-up approach to cognitive ontology revision: Neuroscientists should revise their taxonomies of cognitive constructs on the basis of brain activation patterns across many tasks. We argue that such bottom up proposal is bound to commit a mistake of reification: It treats the abstract mathematical entities uncovered by dimension reduction techniques as if they were real psychological entities. PMID- 27562011 TI - Thiol/disulphide homeostasis levels in erectile dysfunction patients. AB - This study explored the use of thiol/disulphide homeostasis as a novel oxidative stress marker in patients with erectile dysfunction (ED). Fifty-five patients aged 40-57 were divided into two groups: Group I (International Index of Erectile Function [IIEF-5] score between 22 and 25, n = 20) and Group II (IIEF-5 score < 22, n = 35). Blood samples were used to evaluate hormone levels, lipid profile and thiol/disulphide levels. A novel, fully automated method measured plasma native thiol, total thiol and disulphide levels. Mean age, body mass index, total testosterone, HbA1c, triglyceride, atherogenic index (AIP) and total cholesterol levels did not significantly differ between Groups I and II (p > .05). IIEF-5 correlated weakly with native thiol level. Although non-statistically significant, native thiol (431 [SD: 105] MUmol/L vs. 404 [110] MUmol/L) and total thiol (426 [64] MUmol/L vs. 41 [78] MUmol/L) levels were lower in the ED group compared to the controls, and disulphide (14 [11] MUmol/L vs. 18 [9] MUmol/L) levels were higher. Mean disulphide/native thiol and mean disulphide/total thiol ratios did not statistically differ between groups. There was a weak positive correlation between AIP and total cholesterol/HDL and disulphide and disulphide/total thiol ratios. Thiol/disulphide haemostasis levels are not a single factor in ED pathophysiology but may contribute. PMID- 27562013 TI - A Downstream Voyage with Mercury. PMID- 27562012 TI - Gluten-free bread with an addition of freeze-dried red and purple potatoes as a source of phenolic compounds in gluten-free diet. AB - The basis for gluten-free diet is often gluten-free bread, which is usually characterized by a low-nutritional value, and lacks any pro-health properties. Only after an introduction of gluten-free raw materials, containing high level of bioactive compounds it would be possible to obtain the product with a pro-health potential. The aim of the study was to analyze the content of bioactive compounds (total phenolic content, phenolic acids, flavonoids, flavonols, anthocyanins and carotenoids) in gluten-free bread prepared with 5% addition of freeze-dried red and purple potatoes as well as to assess their antioxidant potential. Summarizing, among the analyzed gluten-free breads with an addition of freeze dried red and purple potatoes, the best results could be obtained by using variety Magenta Love (red potato), which provided the highest levels of phenolic compounds and carotenoids and also antioxidant and antiradical activity. PMID- 27562014 TI - Electrokinetic Properties of TiO2 Nanotubular Surfaces. AB - Surface charge is one of the most significant properties for the characterisation of a biomaterial, being a key parameter in the interaction of the body implant with the surrounding living tissues. The present study concerns the systematic assessment of the surface charge of electrochemically anodized TiO2 nanotubular surfaces, proposed as coating material for Ti body implants. Biologically relevant electrolytes (NaCl, PBS, cell medium) were chosen to simulate the physiological conditions. The measurements were accomplished as titration curves at low electrolytic concentration (10(-3) M) and as single points at fixed pH but at various electrolytic concentrations (up to 0.1 M). The results showed that all the surfaces were negatively charged at physiological pH. However, the zeta potential values were dependent on the electrolytic conditions (electrolyte ion concentration, multivalence of the electrolyte ions, etc.) and on the surface characteristics (nanotubes top diameter, average porosity, exposed surface area, wettability, affinity to specific ions, etc.). Accordingly, various explanations were proposed to support the different experimental data among the surfaces. Theoretical model of electric double layer which takes into account the asymmetric finite size of ions in electrolyte and orientational ordering of water dipoles was modified according to our specific system in order to interpret the experimental data. Experimental results were in agreement with the theoretical predictions. Overall, our results contribute to enrich the state-of-art on the characterisation of nanostructured implant surfaces at the bio-interface, especially in case of topographically porous and rough surfaces. PMID- 27562015 TI - Temperature and Exciton Concentration Induced Excimer Emission of 4,4'-Bis(4'' Triphenylsilyl) Phenyl-1,1'-Binaphthalene and Application for Sunlight-Like White Organic Light-Emitting Diodes. AB - This paper demonstrates the influence of temperature, exciton concentration, and electron transportation layers on the excimer emission of a novel deep-blue material: 4,4'-bis(4''-triphenylsilyl) phenyl-1,1'-binaphthalene (SiBN), by studying the photoluminescence and electroluminescence spectra of SiBN-based film. We have further developed sunlight-like and warm-light white organic light emitting diodes (WOLEDs) with high efficiency and wide-range spectra, using SiBN and bis(2-phenylbenzothiozolato-N,C2')iridium(acetylacetonate) (bt2Ir(acac)) as the blue excimer and yellow materials, respectively. The resulting device exhibited an excellent spectra overlap ratio of 82.9 % with sunlight, while the device peak current efficiency, external quantum efficiency, and power efficiency were 18.5 cd/A, 6.34 %, and 11.68 lm/W, respectively, for sunlight-like WOLEDs. PMID- 27562017 TI - Antimicrobial and antioxidant activity of the essential oil from the Carpathian Thymus alternans Klokov. AB - The genus Thymus includes several species that are used as flavouring, food preservative as well as in cosmetics. Their secondary metabolites have been extensively studied for pharmacological effects. Nonetheless, some species are neglected and deserve to be explored for chemical composition and biological activities. This is the case with Thymus alternans, a Carpathian bush used as a food additive and for the preparation of a traditional herbal medicine. In this work, we have analysed the chemical composition of T. alternans essential oil by GC and GC-MS and evaluated its antimicrobial and antioxidant activity by disc diffusion, DPPH, ABTS and FRAP methods, respectively. Results showed that T. alternans belongs to the nerolidol chemotype, being rich of this sesquiterpene alcohol (15.8%) which might contribute to the antimicrobial (particularly effective on C. albicans growth) and antioxidant (weak inhibition on ABTS radical and reducing power) activities observed. PMID- 27562016 TI - Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant. AB - Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (?162) relative to fluconazole (?500), posaconazole oral suspension (?8628) or voriconazole (?6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of ?4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided. PMID- 27562018 TI - Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015. AB - We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate binders from nonbinders in virtual screening and to more accurately predict the ligand binding modes prior to the more computationally expensive FEP calculations of binding affinity. PMID- 27562019 TI - Catalytic Asymmetric Decarboxylative Mannich Reaction of Malonic Acid Half Esters with Cyclic Aldimines: Access to Chiral beta-Amino Esters and Chroman-4-amines. AB - An enantioselective decarboxylative Mannich reaction of malonic acid half esters (MAHEs) with cyclic aldimines has been accomplished by employing the copper(I)/(R,R)-Ph-Box complex as chiral catalyst. The desired beta-amino esters were obtained in good to high yields with excellent enantioselectivities. Furthermore, one of the corresponding Mannich products could be readily transformed into chiral chroman-4-amines without loss of enantioselectivity, which is a key intermediate of the human Bradykinin B1 receptor antagonist. PMID- 27562020 TI - Minimizing the Number of Urological Complications After Kidney Transplant: A Comparative Study of Two Types of External Ureteral Stents. AB - OBJECTIVES: The aim of this study was to evaluate the effects of 2 types of external ureteral stents on the number of urological complications after kidney transplant. MATERIALS AND METHODS: Data were retrospectively collected from 366 consecutive transplants performed between January 2013 and January 2015 in our hospital, in which an external ureteral stent was placed during surgery and removed after 9 days. Urological complications were defined as urinary leakage or ureteral stenosis requiring percutaneous nephrostomy placement. RESULTS: A total of 197 patients received a straight stent with 2 larger side holes (type A; 8F "Covidien" tube; Covidien, Dublin, Ireland) and 169 patients received a single J stent with 7 smaller side holes (type B; 7F "Teleflex" single J stent; Teleflex Medical, Athlone, Ireland). We found a significantly higher number of percutaneous nephrostomy placements with type A stents, with 34 (17%) versus 16 (9%) in type B (P = .030). Reason for percutaneous nephrostomy placement, occurrence of stent dysfunction, and need for early removal (< 8 days) were equal in both groups (P = .397), whereas incidence of rejection and urinary tract infection were higher in type B stent group. Patient and graft survival did not differ between the groups. CONCLUSIONS: Use of the type B stent was associated with less urological complications compared with the type A stent. PMID- 27562022 TI - A moving contact line as a rheometer for nanometric interfacial layers. AB - How a liquid drop sits or moves depends on the physical and mechanical properties of the underlying substrate. This can be seen in the hysteresis of the contact angle made by a drop on a solid, which is known to originate from surface heterogeneities, and in the slowing of droplet motion on deformable solids. Here, we show how a moving contact line can be used to characterize a molecularly thin polymer layer on a solid. We find that the hysteresis depends on the polymerization index and can be optimized to be vanishingly small (<0.07 degrees ). The mechanical properties are quantitatively deduced from the microscopic contact angle, which is proportional to the speed of the contact line and the Rouse relaxation time divided by the layer thickness, in agreement with theory. Our work opens the prospect of measuring the properties of functionalized interfaces in microfluidic and biomedical applications that are otherwise inaccessible. PMID- 27562023 TI - Precipitation behavior of AlxCoCrFeNi high entropy alloys under ion irradiation. AB - Materials performance is central to the satisfactory operation of current and future nuclear energy systems due to the severe irradiation environment in reactors. Searching for structural materials with excellent irradiation tolerance is crucial for developing the next generation nuclear reactors. Here, we report the irradiation responses of a novel multi-component alloy system, high entropy alloy (HEA) AlxCoCrFeNi (x = 0.1, 0.75 and 1.5), focusing on their precipitation behavior. It is found that the single phase system, Al0.1CoCrFeNi, exhibits a great phase stability against ion irradiation. No precipitate is observed even at the highest fluence. In contrast, numerous coherent precipitates are present in both multi-phase HEAs. Based on the irradiation-induced/enhanced precipitation theory, the excellent structural stability against precipitation of Al0.1CoCrFeNi is attributed to the high configurational entropy and low atomic diffusion, which reduces the thermodynamic driving force and kinetically restrains the formation of precipitate, respectively. For the multiphase HEAs, the phase separations and formation of ordered phases reduce the system configurational entropy, resulting in the similar precipitation behavior with corresponding binary or ternary conventional alloys. This study demonstrates the structural stability of single phase HEAs under irradiation and provides important implications for searching for HEAs with higher irradiation tolerance. PMID- 27562024 TI - An overview of CEST MRI for non-MR physicists. AB - The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body's physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts. PMID- 27562025 TI - Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development. AB - Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure. PMID- 27562026 TI - Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin-1E. AB - KEY POINTS: Kv2 channels underlie delayed-rectifier potassium currents in various neurons, although their physiological roles often remain elusive. Almost nothing is known about Kv2 channel functions in medial entorhinal cortex (mEC) neurons, which are involved in representing space, memory formation, epilepsy and dementia. Stellate cells in layer II of the mEC project to the hippocampus and are considered to be space-representing grid cells. We used the new Kv2 blocker Guangxitoxin-1E (GTx) to study Kv2 functions in these neurons. Voltage clamp recordings from mEC stellate cells in rat brain slices showed that GTx inhibited delayed-rectifier K+ current but not transient A-type current. In current clamp, GTx had multiple effects: (i) increasing excitability and bursting at moderate spike rates but reducing firing at high rates; (ii) enhancing after depolarizations; (iii) reducing the fast and medium after-hyperpolarizations; (iv) broadening action potentials; and (v) reducing spike clustering. GTx is a useful tool for studying Kv2 channels and their functions in neurons. ABSTRACT: The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin-1E (GTx; 10-100 nm) in rat brain slices to investigate Kv2 channel functions in mEC layer II stellate cells (SCs). These neurons project to the hippocampus and are considered to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K+ current activating beyond -30 mV but not transient A-type current. In current clamp, GTx (i) had almost no effect on the first action potential but markedly slowed repolarization of late spikes during repetitive firing; (ii) enhanced the after-depolarization (ADP); (iii) reduced fast and medium after hyperpolarizations (AHPs); (iv) strongly enhanced burst firing and increased excitability at moderate spike rates but reduced spiking at high rates; and (v) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC SCs by affecting spike repolarization, after potentials, excitability and spike patterns. GTx is a useful tool and may serve to further clarify Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. The results of the present study may also be important for the accurate modelling of grid cells. PMID- 27562027 TI - Ultrafast Self-Limited Growth of Strictly Monolayer WSe2 Crystals. AB - The controllable synthesis of uniform tungsten diselenide (WSe2 ) is crucial for its emerging applications due to the high sensitivity of its extraordinary physicochemical properties to its layer numbers. However, undesirable multilayer regions inevitably form during the fabrication of WSe2 via the traditional chemical vapor deposition process resulted from the lack of significantly energetically favorable competition between layer accumulation and size expansion. This work innovatively introduces Cu to occupy the hexagonal site positioned at the center of the six membered ring of the WSe2 surface, thus filtrates the undesired reaction path through precisely thermodynamical control and achieves self-limited growth WSe2 crystals. The as-obtained WSe2 crystals are characterized as strictly single-layer over the entire wafer. Furthermore, the strictly self-limited growth behavior can achieve the "win-win" cooperation with the synthesis efficiency. The fastest growth (~15 times of the growth rate in the previous work) of strictly monolayer WSe2 crystals thus far is realized due to the high-efficiency simultaneous selenization process. The as-proposed ultrafast Cu-assisted self-limited growth method opens a new avenue to fabricate strictly monolayer transition metal dichalcogenides crystals and further promotes their practical applications in the future industrial applications. PMID- 27562028 TI - Asymmetric synthesis using chiral-encoded metal. AB - The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R) enantiomer when using (R)-imprinted electrodes and vice versa for the (S) imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID- 27562029 TI - Implications of atmospheric conditions for analysis of surface temperature variability derived from landscape-scale thermography. AB - Thermal infrared (TIR) cameras perfectly bridge the gap between (i) on-site measurements of land surface temperature (LST) providing high temporal resolution at the cost of low spatial coverage and (ii) remotely sensed data from satellites that provide high spatial coverage at relatively low spatio-temporal resolution. While LST data from satellite (LSTsat) and airborne platforms are routinely corrected for atmospheric effects, such corrections are barely applied for LST from ground-based TIR imagery (using TIR cameras; LSTcam). We show the consequences of neglecting atmospheric effects on LSTcam of different vegetated surfaces at landscape scale. We compare LST measured from different platforms, focusing on the comparison of LST data from on-site radiometry (LSTosr) and LSTcam using a commercially available TIR camera in the region of Bozen/Bolzano (Italy). Given a digital elevation model and measured vertical air temperature profiles, we developed a multiple linear regression model to correct LSTcam data for atmospheric influences. We could show the distinct effect of atmospheric conditions and related radiative processes along the measurement path on LSTcam, proving the necessity to correct LSTcam data on landscape scale, despite their relatively low measurement distances compared to remotely sensed data. Corrected LSTcam data revealed the dampening effect of the atmosphere, especially at high temperature differences between the atmosphere and the vegetated surface. Not correcting for these effects leads to erroneous LST estimates, in particular to an underestimation of the heterogeneity in LST, both in time and space. In the most pronounced case, we found a temperature range extension of almost 10 K. PMID- 27562030 TI - Assessing plant senescence reflectance index-retrieved vegetation phenology and its spatiotemporal response to climate change in the Inner Mongolian Grassland. AB - Plant phenology is a key link for controlling interactions between climate change and biogeochemical cycles. Satellite-derived normalized difference vegetation index (NDVI) has been extensively used to detect plant phenology at regional scales. Here, we introduced a new vegetation index, plant senescence reflectance index (PSRI), and determined PSRI-derived start (SOS) and end (EOS) dates of the growing season using Moderate Resolution Imaging Spectroradiometer data from 2000 to 2011 in the Inner Mongolian Grassland. Then, we validated the reliability of PSRI-derived SOS and EOS dates using NDVI-derived SOS and EOS dates. Moreover, we conducted temporal and spatial correlation analyses between PSRI-derived SOS/EOS date and climatic factors and revealed spatiotemporal patterns of PSRI-derived SOS and EOS dates across the entire research region at pixel scales. Results show that PSRI has similar performance with NDVI in extracting SOS and EOS dates in the Inner Mongolian Grassland. Precipitation regime is the key climate driver of interannual variation of grassland phenology, while temperature and precipitation regimes are the crucial controlling factors of spatial differentiation of grassland phenology. Thus, PSRI-derived vegetation phenology can effectively reflect land surface vegetation dynamics and its response to climate change. Moreover, a significant linear trend of PSRI-derived SOS and EOS dates was detected only at small portions of pixels, which is consistent with that of greenup and brownoff dates of herbaceous plant species in the Inner Mongolian Grassland. Overall, PSRI is a useful and robust metric in addition to NDVI for monitoring land surface grassland phenology. PMID- 27562031 TI - Influenza transmission during extreme indoor conditions in a low-resource tropical setting. AB - Influenza transmission occurs throughout the planet across wide-ranging environmental conditions. However, our understanding of the environmental factors mediating transmission is evaluated using outdoor environmental measurements, which may not be representative of the indoor conditions where influenza is transmitted. In this study, we examined the relationship between indoor environment and influenza transmission in a low-resource tropical population. We used a case-based ascertainment design to enroll 34 households with a suspected influenza case and then monitored households for influenza, while recording indoor temperature and humidity data in each household. We show that the indoor environment is not commensurate with outdoor conditions and that the relationship between indoor and outdoor conditions varies significantly across homes. We also show evidence of influenza transmission in extreme indoor environments. Specifically, our data suggests that indoor environments averaged 29 degrees C, 18 g/kg specific humidity, and 68 % relative humidity across 15 transmission events observed. These indoor settings also exhibited significant temporal variability with temperatures as high as 39 degrees C and specific and relative humidity increasing to 22 g/kg and 85 %, respectively, during some transmission events. However, we were unable to detect differences in the transmission efficiency by indoor temperature or humidity conditions. Overall, these results indicate that laboratory studies investigating influenza transmission and virus survival should increase the range of environmental conditions that they assess and that observational studies investigating the relationship between environment and influenza activity should use caution using outdoor environmental measurements since they can be imprecise estimates of the conditions that mediate transmission indoors. PMID- 27562032 TI - Circulating C3 levels predict renal and global outcome in patients with renal vasculitis. AB - Several studies have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis. We aimed to assess the association between baseline serum C3 (sC3) levels and long-term outcomes in patients with renal vasculitis. This retrospective study included 111 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Serum levels of C3 were measured at the onset and the study population was divided into three tertiles according to sC3 concentrations (tertile 1 <106 mg/dl; tertile 2 106-128 mg/dl; tertile 3 >128 mg/dl). Patients with lower sC3 (tertile 1) were compared with those having higher levels of sC3 (tertile 2 and tertile 3). Histological, clinical, and laboratory data were recorded for analysis. The primary end point was the composite of end-stage renal disease (ESRD) and death from any cause. Lower sC3 levels were associated with a higher need for dialysis and lower response rate to treatment (p = 0.04 and p = 0.007, respectively). Renal and global survival at 1 and 5 years was 53 and 46 % in patients with lower sC3 (tertile 1) compared with 72 and 65 % in patients with higher sC3 (upper two tertiles) (p = 0.04). In a multivariate Cox-regression model, when adjusted by renal function and histopatholologic categories, lower sC3 remained as an independent predictor of ESRD and death (HR, 1.9; 95 % CI, 1.1 to 3.4; p = 0.02). Baseline serum C3 levels have an independent prognostic value in predicting long-term renal and global survival in patients with renal vasculitis. PMID- 27562033 TI - Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients. AB - The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616-0.837 and AUC 0.824, p?0.001, 95 % CI 0.690-0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients. PMID- 27562034 TI - Low pretreatment levels of myeloid-related protein-8/14 and C-reactive protein predict poor adherence to treatment with tumor necrosis factor inhibitors in juvenile idiopathic arthritis. AB - Two thirds of patients with juvenile idiopathic arthritis (JIA) treated with tumor necrosis factor (TNF)-alpha inhibitors respond initially, but only about one third of patients achieve clinical remission at follow-up. We evaluated the 1 year response and long-term treatment adherence to TNF inhibitor treatment in JIA patients naive to biologics and investigated if baseline myeloid-related protein (MRP)-8/14 and C-reactive protein (CRP) were predictive of treatment response. One hundred fifty-two patients were included in a unicenter observational, prospective study from 2002 to 2015, excluding patients with systemic-onset JIA. One-year treatment response was evaluated by American College of Rheumatology pediatric (ACR-ped) and by the number of patients achieving inactive disease (ID). Medical charts were reviewed for reasons of treatment withdrawal. After one year of treatment ACR-ped 30, 50, 70, and 90 were achieved by 61, 55, 38, and 10 % of the patients, and 23 % achieved a status of ID. Treatment adherence: 51 % withdrew from treatment due to lack of clinical effect, while 32 % continued treatment or withdrew due to disease remission. Increased MRP-8/14 concentrations at treatment initiation was associated with ID after 1 year (OR 1.55, CI 1.06 2.25, p = 0.02). Treatment withdrawal due to lack of effect was associated with low baseline levels of both MRP-8/14 (685 vs. 1235 ng/ml, p < 0.001) and CRP (0.75 vs. 2.73 mg/l, p < 0.001), verified by multivariable logistic regression analysis (OR 0.51, CI 0.34-0.77/OR 0.63, CI 0.48-0.83). In conclusion, an association was found between ID after 1 year of treatment and increased baseline levels of MRP-8/14. Furthermore, low baseline MRP-8/14 and CRP concentrations were associated with treatment withdrawal due to lack of clinical effect. PMID- 27562035 TI - Serum CXCL4 increase in primary Sjogren's syndrome characterizes patients with microvascular involvement and reduced salivary gland infiltration and lymph node involvement. AB - CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjogren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2-11.18] vs 1.023 ng/ml [0.02-14.45], p < 0.05), particularly in those without anti-La/SSB antibodies (2.89 [1.01-11.18] vs 1.69 ng/ml [0.2-2.72], p < 0.05), while it was lower in pSS patients with a focus score >=1 at lip biopsy (1.44 [0.86-2.1] vs 2.24 ng/ml [1.64-3.25], p < 0.05) and clinically evident lymphadenopathy (1.53 [0.38-1.7] vs 2.08 ng/ml [1.45-3.03], p < 0.05). CXCL4 correlated with disease duration (r = 0.35, p < 0.05) and sE-selectin (r = 0.45, p < 0.01). Patients with Raynaud's phenomenon (RP) had more frequently abnormal CXCL4 levels than patients without RP (11/15 vs 3/21, p < 0.001), enlarged capillaries (14/16 vs 7/23, p < 0.001) and capillary loss at NVC (14/16 vs 6/23, p < 0.001). The hitherto unknown association of increased serum CXCL4 with features of microvascular impairment in pSS, along with the negative association with features of lymphocytic response (i.e., the absence of subset disease-specific autoantibodies, a low focus score, and the absence of lymphadenopathy) suggest clarifying the possible implication of this chemokine in pSS pathogenesis in larger studies. PMID- 27562037 TI - Identifying Common Practice Elements to Improve Social, Emotional, and Behavioral Outcomes of Young Children in Early Childhood Classrooms. AB - Educators are increasingly being encouraged to implement evidence-based interventions and practices to address the social, emotional, and behavioral needs of young children who exhibit problem behavior in early childhood settings. Given the nature of social-emotional learning during the early childhood years and the lack of a common set of core evidence-based practices within the early childhood literature, selection of instructional practices that foster positive social, emotional, and behavioral outcomes for children in early childhood settings can be difficult. The purpose of this paper is to report findings from a study designed to identify common practice elements found in comprehensive intervention models (i.e., manualized interventions that include a number of components) or discrete practices (i.e., a specific behavior or action) designed to target social, emotional, and behavioral learning of young children who exhibit problem behavior. We conducted a systematic review of early childhood classroom interventions that had been evaluated in randomized group designs, quasi-experimental designs, and single-case experimental designs. A total of 49 published articles were identified, and an iterative process was used to identify common practice elements. The practice elements were subsequently reviewed by experts in social-emotional and behavioral interventions for young children. Twenty-four practice elements were identified and classified into content (the goal or general principle that guides a practice element) and delivery (the way in which a teacher provides instruction to the child) categories. We discuss implications that the identification of these practice elements found in the early childhood literature has for efforts to implement models and practices. PMID- 27562036 TI - A Behavior-Based Intervention That Prevents Sexual Assault: the Results of a Matched-Pairs, Cluster-Randomized Study in Nairobi, Kenya. AB - DESIGN: The study's design was a cluster-randomized, matched-pairs, parallel trial of a behavior-based sexual assault prevention intervention in the informal settlements. METHODS: The participants were primary school girls aged 10-16. Classroom-based interventions for girls and boys were delivered by instructors from the same settlements, at the same time, over six 2-h sessions. The girls' program had components of empowerment, gender relations, and self-defense. The boys' program promotes healthy gender norms. The control arm of the study received a health and hygiene curriculum. The primary outcome was the rate of sexual assault in the prior 12 months at the cluster level (school level). Secondary outcomes included the generalized self-efficacy scale, the distribution of number of times victims were sexually assaulted in the prior period, skills used, disclosure rates, and distribution of perpetrators. Difference-in differences estimates are reported with bootstrapped confidence intervals. RESULTS: Fourteen schools with 3147 girls from the intervention group and 14 schools with 2539 girls from the control group were included in the analysis. We estimate a 3.7 % decrease, p = 0.03 and 95 % CI = (0.4, 8.0), in risk of sexual assault in the intervention group due to the intervention (initially 7.3 % at baseline). We estimate an increase in mean generalized self-efficacy score of 0.19 (baseline average 3.1, on a 1-4 scale), p = 0.0004 and 95 % CI = (0.08, 0.39). INTERPRETATION: This innovative intervention that combined parallel training for young adolescent girls and boys in school settings showed significant reduction in the rate of sexual assault among girls in this population. PMID- 27562040 TI - [The current status and rethinking of palliative care]. PMID- 27562038 TI - Adolescent Alcohol Use: Protective and Predictive Parent, Peer, and Self-Related Factors. AB - Adolescent alcohol use has been linked with a multitude of problems and a trajectory predictive of problematic use in adulthood. Thus, targeting factors that enhance early prevention efforts is vital. The current study highlights variables that mitigate or predict alcohol use and heavy episodic drinking. Using Monitoring the Future (MTF) data, multiple path analytic models revealed links between parental involvement and alcohol abstinence and initiation. Parental involvement predicted enhanced self-esteem and less self-derogation and was negatively associated with peer alcohol norms for each MTF grade sampled, with stronger associations for 8th and 10th graders than 12th graders. For younger groups, self-esteem predicted increased perceptions of alcohol risk and reduced drinking. Self-derogation was associated with peers' pro-alcohol norms, which was linked to lower risk perceptions, lower personal disapproval of use, and increased drinking. Peer influence had a stronger association with consumption for 8th and 10th graders, whereas 12th graders' drinking was related to personal factors of alcohol risk perception and disapproval. In all grades, general alcohol use had a strong connection to heavy episodic drinking within the past 2 weeks. Across-grade variations in association of parent, peer, and personal factors suggest the desirability of tailored interventions focused on specific factors for each grade level, with the overall goal of attenuating adolescent alcohol use. PMID- 27562041 TI - [Etiology analysis of 522 hospitalized cases with Cushing syndrome]. AB - OBJECTIVE: To summarize the characteristics of the etiology distribution of Cushing syndrome (CS) patients in Chinese PLA general hospital during the past 20 years. METHODS: All data of CS patients admitted to Chinese PLA General Hospital between 1995 and 2014 were collected. The sex ratio of patients, visiting age, final diagnosis were retrospectively analyzed. RESULTS: From January 1995 to December 2014, 522 patients with CS were admitted, of which, 134 (25.67%) were males and 388(74.33%) were females. The overall mean age was (42+/-13) years old. 46.36% of the cases were adrenocorticotropic hormone (ACTH) dependent, and ACTH independent CS accounted for 53.64%. At the 41-60 age group, the proportion of ACTH independent CS was higher than that of ACTH independent CS.The proportions of ACTH-independent macronodular adrenal hyperplasia (AIMAH), ectopic ACTH syndrome and adrenal cortical carcinoma were higher in male group than in female group. The number of CS patients was gradually increased during the past 20 years. The proportion of ACTH independent CS was increased (from 32.8% to 60.4%). The proportion of ACTH dependent CS was declined (from 67.2% to 39.6%). CONCLUSION: The etiology spectrum of CS has changed. There was significant gender related, age-related difference of etiology distribution in patients with CS. PMID- 27562039 TI - The Cytomegalovirus protein pUL37*1 targets mitochondria to mediate neuroprotection. AB - There is substantial evidence that mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson disease (PD). This contribution probably encompasses defects of oxidative phosphorylation, mitochondrial turnover (mitophagy), mitochondrial derived oxidative stress, and apoptotic signalling. Human cytomegalovirus immediate-early protein pUL37 * 1 induces Bax mitochondrial translocation and inactivation to prevent apoptosis. Over-expressing pUL37 * 1 in neuronal cells protects against staurosporin and 6-hydroxydopamine induced apoptosis and cell death. Protection is not enhanced by bax silencing in pUL37 * 1 over-expressing cells, suggesting a bax-dependent mechanism of action. pUL37 * 1 increases glycolysis and induces mitochondrial hyperpolarization, a bax independent anti-apoptotic action. pUL37 * 1 increases glycolysis through activation of phosphofructokinase by a calcium-dependent pathway. The dual anti apoptotic mechanism of pUL37 * 1 may be considered a novel neuroprotective strategy in diseases where mitochondrial dysfunction and apoptotic pathways are involved. PMID- 27562043 TI - [Value of ratio of sensory nerves conductive velocity along palm-median finger/wrist-palm in diagnosing the carpal tunnel syndrome]. AB - OBJECTIVE: To Verify the value of the ratio of sensory nerves conductive velocity along palm-median finger /wrist-palm minus 1 for diagnosis of the mild-moderate carpal tunnel syndrome(CTS). METHODS: The different value between 1 and the ratio of sensory nerves conductive velocity along palm-median finger/wrist-palm was defined as index-CTS which was used to assess the severity of CTS.The index-CTS of 100 palms from healthy controls and 58 palms from mild-moderate CTS patients were calculated and compared.Multiple regression was used to identify the relative factors of index-CTS.The ROC curve was used to evaluate the sensitivity and specificity of index-CTS at different values. RESULTS: The value of index-CTS from healthy controls and patients both fitted Gaussian distribution.The mean value were -0.053+/-0.042 vs 0.055+/-0.074 in the controls and the patients respectively.The difference was statistically significant between the two groups by T-test(P<0.001). Multiple regression analysis showed that Tinel sign, Phalen sign, laterality, clinical grade, electrical grade were identifiable factors related to index-CTS.When index-CTS was over 0.001 and IV-DL over 0.395 ms , specificity of diagnosis by both can get 92%, but index-CTS showed more higher sensitivity(98.3% vs 89.7%). CONCLUSIONS: Rising index-CTS could be the most significant electrophysiological feature in CTS.It can be used as a sensitive marker to assess the extent of conduction block of median nerve in carpal tunnel. PMID- 27562042 TI - [Use early morning serum cortisollevel to evaluate the effect of Cushing's disease after transsphenoidal surgery]. AB - OBJECTIVE: To predict the therapeutic effect of Cushing's disease after transsphenoidal surgery by using morning serum cortisol level. METHODS: The clinical data of 275 cases that had transsphenoidal surgery in Peking Union Medical College Hospital from 2010 to 2014 were analyzed retrospectively.Early morning serum cortisol level less than 140 nmol/L 3 days postoperation was usedto predict endocrinological remission. And long-term efficacy was evaluated by follow-up. RESULTS: Of the 275 patients, there were 49 males and 226 females; average age was 36.5 years old.Remission wasconfirmed in 201 cases, the remission rate was 73.1%, and 8 cases recurrent duringfollow-up.There were 17 macroadenomas, theremission rate was 47.1%; 258 microadenomas and MRI negative adenomas, the remission rate was 74.8%.And 43 recurrent cases had reoperations; the remission rate was 46.5%. CONCLUSION: Early morningserum cortisol 3 days post operation can evaluate the effectof transsphenoidal surgery, but even if the level of cortisol is less than 140 nmol/L, there is still tumor recurrence.Patients should be follow-up for a lifetime. PMID- 27562044 TI - [Comparison of calcar replacement arthroplasty and Intertan nail in treatment of intertrochanteric fracture in the aged]. AB - OBJECTIVE: To compare the clinical efficacy between calcar replacement arthroplasty and InterTan nail in treatment of intertrochanteric fractures in the aged. METHODS: From January 2008 to July 2013, a total of 58 elderly patients with intertrochanterie fracture , had been treated in Department of Orthopaedics, Tianjin Occupational Diseases Control and Treatment Hospital, were retrospectively compared.Half of them were treated with calcar replacement arthroplasty and half with InterTan nails.In the calcar replacement arthroplasty group, there were 8 men and 21 women, with an average age of (85.3+/-4.9) years, there were 8 A1, 16 A2 and 5 A3 fractures according to the AO classification.In the InterTan nail group, there were 10 men and 19 women, with an average age of (86.1+/-5.6) years, there were 11 A1, 15 A2 and 3 A3 fractures according to the AO classification.The 2 groups were compared in terms of the duration of the operation, intraoperative blood loss, hospitalization time, time of off-bed activity, complications, mortality rate, Harris hip score, short form 36 questionnaire score and ADL score. RESULTS: Twenty-seven patients in the calcar replacement arthroplasty group and twenty-six patients in the patients in each group were followed up InterTan nail group were follow-up for a period of 24 months.There were no significant differences between the 2 groups regarding hospitalization time, complications, mortality rate, Harris hip score, short form 36 questionnaire score and ADL score(P>0.05). However, the operative time, intraoperative blood loss, and the time of off-bed activity for the calcar replacement arthroplasty and InterTan nail groups was respectively (78+/-29) minutes vs (59+/-32) minutes, (316+/-185) ml vs (108+/-97) ml, and (15+/-5.8) days vs (32+/-12.7) days, all of them with a significant difierence(P<0.05). CONCLUSION: The patients in the calcar replacement arthroplasty group suffered longer operative time and more blood loss, but they can obtain early off-bed activity.The hospitalization time, complications, mortality rate, hip function and quality of Life between the two were the same. PMID- 27562045 TI - [Mechanism of the Piezo1 protein-induced apoptosis of the chondrocytes through the MAPK/ERK1/2 signal pathway]. AB - OBJECTIVE: To invstigate the mechanism of new mechanically-activated cation channel protein (Piezo1) can cause the apoptosis of the human chondrocytes under compressive loading, using a Flexercell unit by activating classical Mitogen activated protein kinase (MAPK) signal pathyway(ERK1/2). METHODS: Primary human chondrocytes were isolated, cultured, and then subjected to the static compressive loading for 0, 2, 12, 24, 48 h, respectively.The expressions of Piezo1 and the ERK1/2 were assessed by reverse transcription-polymerase chain reaction(PT-PCR), as well as the apoptosis gene B cell lymphoma/leukemia-2(Bcl-2) Bel-associated X protein(Bax). In addition, Piezo1inhibitor, Grammostola spatulata mechanotoxin 4(GsMTx4), was used to block Piezo1, served as a positive control.The immunofluorescence was used to locate the expression of Piezo1 protein and ERK1/2.AnnexinV-PI was used to detect the apoptosis of chondrocytes. RESULTS: The expression of the Piezo1 in chondrocytesis was weak, the 12 h group was significant increased(0.198 1 vs 0.021 4, P<0.05), the 24 h group was the highest expression while the expression of the 48 h group was lower than the 24 h group, as well as the ERK1/2, Bcl-2 and caspase3.The result of AV-PI had shown that the 2 h group had increased early stage of apoptosis.The 12 h group had increased late stage of apoptosis, and the 24 h group's apoptotic rate was the highest, while the apoptotic rate of the 48 h group was lower than the 24 h group(0.497 1 vs 0.743 1, q=0.035 9). The GsMTx4 could inhibit the late stage of apoptosis, and the location of the Piezo1 was expressed in the nucleus and cytoplasm of the chondrocytes. CONCLUSIONS: Piezo1 plays an important role in the apoptosis of the human chondrocyte through the classic MAPK/ERK1/2 signal pathway. PMID- 27562046 TI - [Imaging features analysis of Erdheim-Chester]. AB - OBJECTIVE: To investigate the imaging features of Erdheim-Chester. METHODS: A total of 7 patients with ECD confirmed by pathology were analyzed retrospectively.And the DR(n=5), CT(n=6, 3 patients underwent enhanced scan), MR(n=4, 2 patients underwent enhanced scan) and SPECT (n=3) features were observed. RESULTS: Among 7 cases of ECD, four cases of DR images showed luffa cystic changes.Five cases of CT images showed bone dissolved, four showed peripheral localized sclerosis, one showed symmetric sclerosis, No enhancement was found on CT scan.Four cases of MR images, three occurred as long T1 and long T2 signal, one occurred as short T1 and long T2 signal, and inhomogeneous enhancement.One case in soft tissue occurred as long T1 and long T2 signal, and inhomogeneous enhancement.Three cases of SPECT images were characterized by radioactive nuclide concentration of diseased region. CONCLUSION: When ECD lesions located in capitulum and metaphysis, most images of DR and CT show bone dissolved and peripheral localized sclerosis; MRI findings are complicated, the reason might be different proportion of mature and immature lipid components.SPECT would be a kind of effective measure of finding hidden lesion and monitoring curative effect. PMID- 27562047 TI - [Predictive value of sonographic features in preoperative evaluation of medullary thyroid carcinoma]. AB - OBJECTIVE: To summarize ultrasound features associated with medullary thyroid carcinoma (MTC) and investigate the predictive value of ultrasonography in preoperative diagnosis of MTC. METHODS: The sonographic and clinical data were studied in a series of nodules histologically proven as MTC collected from January 1993 to January 2013. RESULTS: A total of 86 patients (92 nodules proven as MTC) were enrolled in the study with an average age of (47+/-12) years.Among the MTCs, 21.7%(20/92) were excluded because of missing data and the remained 78.3%(72/92) had complete data with the average diameter of (2.1+/-1.3) cm.The common US findings for MTC were solid, hypoechogenicity, regular sharp, well defined margin, AP/ TR<1 and calcification (mostly microcalcification). Calcification and vascularization were more common in MTC nodules(48.6% vs 5.6%, P=0.001). Nodules with enlargement of cervical lymph node tended to be undergone FNAB(76.0% vs 55.3%, P=0.084), and ill-defined margin was more common in MTC nodules with cervical lymph node metastasis(36.4% vs 12.8%, P=0.009). CONCLUSION: Despite having a few US features closely linked to the malignant nodules such as solid, hypoechogenicity and with microcalcification, the MTC nodules also have specific US imaging characteristics as regular sharp, well-defined margin and AP/ TR<1. PMID- 27562048 TI - [A comparative study on characterizations of genetic recombination hotspots in PPARG gene between Kirgiz and Uyghur ethnic groups in Xinjiang]. AB - OBJECTIVE: To investigate the characterizations of genetic recombination hotspots and linkage disequilibrium (LD) patterns in peroxisome proliferative activated receptor gamma (PPARG) gene in Kirgiz and Uyghur ethnic groups. METHODS: Blood samples were collected from 100 Kirgiz (50 healthy controls and 50 patients with type 2 diabetes mellitus) residents in Halajun County, Artux City, Kizilsu Kirgiz Autonomous Prefecture, Xinjiang in August 2013, and 50 healthy Uyghur residents in Hotan Prefecture of Xinjiang Uygur Autonomous Region in May 2012.Thirty-one tagSNPs in PPARG gene were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) method.The recombination hotspots and LD patterns within the PPARG gene were estimated by analyzing the SNP genotying data using the Hotspot Fisher program and Haploview software, respectively. RESULTS: Eighteen tagSNPs (rs1151999, rs1175540, rs1875796, rs1899951, rs2292101, rs2921190, rs2938397, rs2959272, rs2959273, rs2972162, rs3856806, rs4135247, rs4135275, rs709151, rs4135354, rs6805419, rs17036700 and rs4135304) were same with relatively higher recombination rates between the patients with type 2 diabetes mellitus (T2DM) and healthy controls of Kirgiz ethnic group, and healthy controls of Uyghur ethnic group.Five haplotype blocks with LD coefficient D' value of 1, indicating no genetic recombination occurred within the region, were observed in the healthy controls of Kirgiz ethnic groups, whereas five haplotype blocks with LD coefficient D' value less than 1 were observed in the Kirgiz patients with T2DM, indicating historical recombination events occurred within the region.Four haplotype blocks with LD coefficient D' value of 1 were observed in the Uyghur healthy controls, indicating no genetic recombination occurred within the region.There were significantly different recombination hotspot profiles between the Kirgiz, Uyghur, Utah residents with Northern and Western European ancestry (CEU), Yoruban in Ibadan, Nigeria (YRI) and Han Chinese in Beijing (CHB) and Japanese in Tokyo (JPT) samples.There are six recombination hotspots in the HapMap profile of genetic recombination.The last 5 SNPs within the PPARG gene were shown with lower recombination rates in the Kirgiz, whereas no recombination hotspot was found in the Uyghur. CONCLUSIONS: Variable recombination rates may be present in certain chromosome region between patients and healthy controls within the same or between the different ethnic groups.There may be presence of recombination hotspots of ethnic specificity and with variable recombination rates. PMID- 27562049 TI - [Effect of uncoupling protein 2 on high-glucose induced mitochondrial damage and apoptosis of cardiomyocytes]. AB - OBJECTIVE: To observe the expression of uncoupling protein (UCP2) and its effect on modulation of mitochondrial function and apoptosis of cardiomyocytes exposed to high-glucose. METHODS: AC16 cardiomyoctyes were randomly divided into normal glucose group (NG), high-glucose group (HG), HG+ UCP2 siRNA group and HG+ negative control siRNA group.The expression of UCP2, succinodehydrogenase(SDH) activity, ATP content, reactive oxygen species (ROS) generation, cell apoptotic rate, caspase-3 activity and cell viability were detected. RESULTS: Compared with the cardiomyocytes in NG group, the ROS production, apoptotic rate and caspase-3 activity were significantly increased in HG group, accompanying with the decreases in SDH activity, ATP content and cell viability.The expression of UCP2 was increased in HG group. Furthermore, UCP2 siRNA inhibited the expression of UCP2 and aggravated high-glucose induced the ROS production (37.96+/-1.08 vs 27.68+/-0.60, P<0.05), cell apoptosis ((25.68+/-0.78)% vs (17.80+/-0.99)%, P<0.05), caspase-3 activity ((2.71+/-0.13)% vs (2.14+/-0.28)%, P<0.05) and cell inactivation (0.74+/-0.04 vs 0.62+/-0.03, P<0.05), but had no impact on SDH activity and ATP content in cardiomyocytes. CONCLUSION: The up-regulation of UCP2 expression in cardiomyocytes, induced by high-glucose, maybe a protective mechanism for the mitochondrial damage, and UCP2 may inhibit high-glucose induced cardiomyocytes apoptosis. PMID- 27562050 TI - [Protective effects of oxycodone on lipopolysaccharide-induced acute lung injury in rats]. AB - OBJECTIVE: To analyze the role of oxycodone in acute lung injury(ALI) induced by lipopolysaccharide (LPS) in rats. METHODS: Male SD rats were randomly allocated into 4 groups: control group, oxycodone group, LPS group, LPS+ oxycodone group. The effects of oxycodone on LPS-induced neutrophils influx, inflammatory cytokines release, pulmonary edema, apoptotic cell were examined. In addition, the toll-like receptor 4 (TLR4) in lung tissues was detected by Western blotting. RESULTS: Oxycodone significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratio, was markedly decreased by oxycodone(5.60+/-0.24 vs 6.80+/-0.27, P<0.05 ). Moreover, oxycodone decreased the productions of the inflammatory cytokines including IL-1beta, TNF-alpha, HMGB-1((1 208+/-18)pg/ml, (1 660+/-14) pg/ml, (61+/-4) pg/ml , all P<0.05). Oxycodone treatment also reduced the concentration of apoptosis in lung tissues(18.6%+/-0.5%, P<0.05). Furthermore, the expression of TLR4 was significantly suppressed by oxycodone treatment in lung tissues(1.20+/-0.15, P<0.05). CONCLUSIONS: Oxycodone exerts protective effects on LPS-induced ALI in rats. The potential mechanism of this action may attribute partly to the inhibition of TLR4 activation. PMID- 27562051 TI - [Impact of olmesartan medoxomil on atherosclerosis lesions in apolipoprotein E knockout mice]. AB - OBJECTIVE: To investigate the effect and possible mechanisms of olmesartan medoxomil on atherosclerosis of apolipoprotein E knockout (ApoE(-/-)) mice. METHODS: Sixteen 6-week-old male ApoE(-/-) mice were randomly divided into atherosclerosis model group fed with high fat diet, and olmesartan medoxomil intervention group fed with high fat diet and olmesartan medoxomil (10 mg.kg( 1).day(-1,) per gavage). Eight C57BL/6 mice were fed with normal diet, and treated for 12 weeks.The blood pressure and the serum level of lipid were detected; the aorta were removed, oil red staining for plaque area, Hematoxylin and eosin (HE) staining for plaque morphology, Elastica van Gieson (EVG) staining for elastin, and picrosirius red (PSR) for collagen respectively; and the expression of cathepsin S (Cat S), smooth action protein (ASMA) and macrophage surface molecule-3 (Mac-3) were detected by immunohistochemisty analysis. RESULTS: Serum cholesterol and low density lipoprotein levels were significantly higher in atherosclerosis model group than in control group[(15.08+/-1.64) vs (2.06+/-0.15) mmol/L, (15.60+/-1.05) vs (0.00+/-0.00) mmol/L] (all P<0.01), while triglyceride level was similar between the two group.In contrast to model group, the mice in intervention group showed no statistical difference in blood pressure and plasma lipid levels, while the plaque areas in the aorta were significantly decreased (P<0.05) as well as the expression of Cat S and Mac-3[(2.4+/-1.2) vs (8.8+/-3.2)%, (2.2+/-1.2) vs (7.2+/-2.8)%] (all P<0.01). In addition, the elastin levels, collagen contents, and the expression of ASMA remained significantly higher compared with model group (P<0.05). CONCLUSION: Olmesartan medoxomil could slow down the atherosclerosis process, the possible mechanism was implicated with the suppression of Cat S and decreased inflammatory responses alongside the increased elastin and collagen contents. PMID- 27562052 TI - Can severity of aortic stenosis be determined despite absent contractile reserve in low-flow low-gradient aortic stenosis? AB - A 79-year-old man presented with increasing breathlessness and his echocardiogram revealed severe left ventricular systolic dysfunction and low-flow low-gradient aortic stenosis. Low-dose dobutamine stress echocardiography revealed the absence of contractile reserve (increase of stroke volume by >=20% did not occur). The test would have therefore been inconclusive. However, the attainment of normal flow (FR>=200 mL/s) during dobutamine stress enabled the diagnosis of true severe aortic stenosis. PMID- 27562053 TI - Fracture Behavior of Minimally Invasive, Posterior, and Fixed Dental Prostheses Manufactured from Monolithic Zirconia. AB - OBJECTIVES: To compare ultimate fracture load (Fu ), load at first damage (F1d ), and fracture pattern for posterior fixed dental prostheses (FDPs) manufactured from translucent, yttria-stabilized zirconia polycrystal. METHODS: Premolar-size FDPs in 4 test groups (n = 16/group) were constructed as veneered complete crown retained (group 1), monolithic complete crown-retained (group 2), monolithic partial veneer crown-retained (group 3), or monolithic resin-bonded (group 4) prostheses with minimum zirconia wall thickness (0.5 mm). Adhesively cemented to metal abutments, half of the prostheses were artificially aged by use of 10,000 thermocycles (6.5 degrees C/60 degrees C) and 1,200,000 chewing cycles (F = 108 N), before fracture loading. Statistics included two-way non-parametric ANOVA and Dunn-Bonferroni post-hoc tests (alpha = 0.05). RESULTS: None of the restorations failed during artificial aging. Fu was affected by test group (p < 0.001); F1d was also affected by the factor combination of test group and aging (p = 0.001 for test group; p = 0.049 for test group*aging). Mean Fu for all groups exceeded 1000 N; it was comparable for group 1 and group 2 and statistically significantly higher for group 2 and group 3 than for group 4 (p < 0.01). Fracture usually occurred through the retainer wall. F1d = 200 N was determined for individual samples in group 1 (chipping) and group 3 (local debonding). CONCLUSIONS: Fu of all the restorations was adequate for clinical use. Complications might, however, be expected at forces below 500 N for veneered prostheses (chipping) as well as for monolithic partial veneer crown-retained prostheses (local debonding). CLINICAL SIGNIFICANCE: With regard to fracture behavior, all-ceramic complete crown-retained fixed dental prostheses (FDP) manufactured from monolithic zirconia, with a retainer wall thickness of 0.5 mm, might be suitable for use as a conservative alternative to their veneered counterparts in the rehabilitation of posterior tooth loss. Monolithic zirconia resin-bonded FDP might, moreover, be a viable alternative to resin-bonded FDPs with metal adhesive retainers in posterior arches, with improved esthetics and biocompatibility. The performance of both should, however, be verified in clinical trials. (J Esthet Restor Dent 28:367-381, 2016). PMID- 27562054 TI - Health Effects of Unemployment in Europe During the Great Recession: The Impact of Unemployment Generosity. AB - Social and economic security could be particularly important for health among the unemployed. Nevertheless, knowledge is still lacking as to whether and how different policy contexts affect health when people move into unemployment. This article investigates whether and to what degree the unemployment generosity explains why individual health effects of unemployment vary across Europe. The 2008-2011 longitudinal panel of the European Union statistics on income and living conditions (EU-SILC) and fixed-effects models are used to estimate the individual effects of unemployment on self-rated health (SRH). Social spending on unemployment is used as a proxy for unemployment generosity. The results show that unemployment generosity is associated with reduced negative effects of unemployment on SRH. For every increase in adjusted purchasing power standard spending, the negative effect of unemployment on SRH is reduced by 0.003 (SE = 0.001) and the change in SRH is improved by 0.002 (SE = 0.001) for each year following the transition, after controlling for time-variant confounders at the individual level and unemployment rate at the macro level. The association between spending on unemployment and cross-national differences in individual health changes that occur as people enter unemployment provides a robust indication of the mitigating health effects of unemployment generosity. PMID- 27562055 TI - Generation of a macroscopic entangled coherent state using quantum memories in circuit QED. AB - W-type entangled states can be used as quantum channels for, e.g., quantum teleportation, quantum dense coding, and quantum key distribution. In this work, we propose a way to generate a macroscopic W-type entangled coherent state using quantum memories in circuit QED. The memories considered here are nitrogen vacancy center ensembles (NVEs), each located in a different cavity. This proposal does not require initially preparing each NVE in a coherent state instead of a ground state, which should significantly reduce its experimental difficulty. For most of the operation time, each cavity remains in a vacuum state, thus decoherence caused by the cavity decay and the unwanted inter-cavity crosstalk are greatly suppressed. Moreover, only one external-cavity coupler qubit is needed, which simplifies the circuit. PMID- 27562056 TI - Feeding during the resting phase causes profound changes in physiology and desynchronization between liver and muscle rhythms of rats. AB - Shiftworkers run an increased risk of developing metabolic disorders, presumably as a result of disturbed circadian physiology. Eating at a time-of-day that is normally dedicated to resting and fasting, may contribute to this association. The hypothalamus is the key brain area that integrates different inputs, including environmental time information from the central biological clock in the suprachiasmatic nuclei, with peripheral information on energy status to maintain energy homeostasis. The orexin system within the lateral hypothalamus is an important output of the suprachiasmatic nuclei involved in the control of sleep/wake behavior and glucose homeostasis, among other functions. In this study, we tested the hypothesis that feeding during the rest period disturbs the orexin system as a possible underlying contributor to metabolic health problems. Male Wistar rats were exposed to an 8-week protocol in which food was available ad libitum for 24-h, for 12-h during the light phase (i.e., unnatural feeding time) or for 12-h during the dark phase (i.e., restricted feeding, but at the natural time-of-day). Animals forced to eat at an unnatural time, i.e., during the light period, showed no changes in orexin and orexin-receptor gene expression in the hypothalamus, but the rhythmic expression of clock genes in the lateral hypothalamus was absent in these animals. Light fed animals did show adverse changes in whole-body physiology and internal desynchronization of muscle and liver clock and metabolic gene expression. Eating at the 'wrong' time-of-day thus causes internal desynchronization at different levels, which in the long run may disrupt body physiology. PMID- 27562057 TI - Dysregulation of redox pathways in liver fibrosis. AB - Reactive oxygen species are implicated in physiological signaling and cell fate decisions. In chronic liver diseases persistent and increased production of oxidative radicals drives a fibrogenic response that is a common feature of disease progression. Despite our understanding the biology of the main prooxidant enzymes, their targets, and antioxidant mechanisms in the liver, there is still lack of knowledge concerning their precise role in the pathogenesis of fibrosis. This review will examine the role of physiological redox signaling in the liver, provide an overview on recent advances in prooxidant and antioxidant pathways that are dysregulated during fibrosis, and highlight possible novel treatment targets. PMID- 27562058 TI - Anti-inflammatory effects of Bifidobacterium longum subsp infantis secretions on fetal human enterocytes are mediated by TLR-4 receptors. AB - The therapeutic and preventive application of probiotics for necrotizing enterocolitis (NEC) has been supported by more and more experimental and clinical evidence in which Toll-like receptor 4 (TLR-4) exerts a significant role. In immune cells, probiotics not only regulate the expression of TLR-4 but also use the TLR-4 to modulate the immune response. Probiotics may also use the TLR-4 in immature enterocytes for anti-inflammation. Here we demonstrate that probiotic conditioned media (PCM) from Bifidobacterium longum supp infantis but not isolated organisms attenuates interleukin-6 (IL-6) induction in response to IL 1beta by using TLR-4 in a human fetal small intestinal epithelial cell line (H4 cells), human fetal small intestinal xenografts, mouse fetal small intestinal organ culture tissues, and primary NEC enterocytes. Furthermore, we show that PCM, using TLR-4, downregulates the mRNA expression of interleukin-1 receptor associated kinase 2 (IRAK-2), a common adapter protein shared by IL-1beta and TLR 4 signaling. PCM also reduces the phosphorylation of the activator-protein 1 (AP 1) transcription factors c-Jun and c-Fos in response to IL-1beta stimulation in a TLR-4-dependent manner. This study suggests that PCM may use TLR-4 through IRAK-2 and via AP-1 to prevent IL-1beta-induced IL-6 induction in immature enterocytes. Based on these observations, the combined use of probiotics and anti-TLR-4 therapy to prevent NEC may not be a good strategy. PMID- 27562060 TI - Aberrant fecal flora observed in guinea pigs with pressure overload is mitigated in animals receiving vagus nerve stimulation therapy. AB - Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. Stimulation of the vagus nerve, which innervates the heart and abdominal organs, is proving to be an effective therapeutic in heart failure. We hypothesized that cervical vagus nerve stimulation (VNS) could alter fecal flora and prevent aberrations observed in fecal samples from heart failure animals. To determine whether microbial abundances were altered by pressure overload (PO), leading to heart failure and VNS therapy, a VNS pulse generator was implanted with a stimulus lead on either the left or right vagus nerve before creation of PO by aortic constriction. Animals received intermittent, open-loop stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end-systolic and diastolic volumes, as well as cardiac output, were impaired in PO animals compared with baseline. VNS mitigated these effects. Metagenetic analysis was then performed using 16S rRNA sequencing to identify bacterial genera present in fecal samples. The abundance of 10 genera was significantly altered by PO, 8 of which were mitigated in animals receiving either left- or right-sided VNS. Metatranscriptomics analyses indicate that the abundance of genera that express genes associated with ATP-binding cassette transport and amino sugar/nitrogen metabolism was significantly changed following PO. These gut flora changes were not observed in PO animals subjected to VNS. These data suggest that VNS prevents aberrant gut flora following PO, which could contribute to its beneficial effects in heart failure patients. PMID- 27562059 TI - Anti-TNFalpha alters the natural history of experimental Crohn's disease in rats when begun early, but not late, in disease. AB - Anti-TNFalpha therapy decreases inflammation in Crohn's disease (CD). However, its ability to decrease fibrosis and alter the natural history of CD is not established. Anti-TNF-alpha prevents inflammation and fibrosis in the peptidoglycan-polysaccharide (PG-PS) model of CD. Here we studied anti-TNF-alpha in a treatment paradigm. PG-PS or human serum albumin (HSA; control) was injected into bowel wall of anesthetized Lewis rats at laparotomy. Mouse anti-mouse TNF alpha or vehicle treatment was begun day (d)1, d7, or d14 postlaparotomy. Rats were euthanized d21-23. Gross abdominal and histologic findings were scored. Cecal levels of relevant mRNAs were measured by quantitative real-time PCR. There was a stepwise loss of responsiveness when anti-TNFalpha was begun on d7 and d14 compared with d1 that was seen in the percent decrease in the median gross abdominal score and histologic inflammation score in PG-PS-injected rats [as %decrease; gross abdominal score: d1 = 75% (P = 0.003), d7 = 57% (P = 0.18), d14 = no change (P = 0.99); histologic inflammation: d1 = 57% (P = 0.006), d7 = 50% (P = 0.019), d14 = no change (P = 0.99)]. This was also reflected in changes in IL-1beta, IL-6, TNF-alpha, IGF-I, TGF-beta1, procollagen I, and procollagen III mRNAs that were decreased or trended downward in PG-PS-injected animals given anti-TNF-alpha beginning d1 or d7 compared with vehicle-treated rats; there was no effect if anti-TNF-alpha was begun d14. This change in responsiveness to anti TNFalpha therapy was coincident with a major shift in the cytokine milieu observed on d14 in the PG-PS injected rats (vehicle treated). Our data are consistent with the clinical observation that improved outcomes occur when anti TNF-alpha therapy is initiated early in the course of CD. PMID- 27562061 TI - Dual effects of a high-protein diet on DSS-treated mice during colitis resolution phase. AB - The impact of the dietary protein level on the process of colonic mucosal inflammation and subsequent recovery remains largely unknown. In this study, we fed DSS-treated mice with either a normoproteic (NP) or a high-protein (HP) isocaloric diet from the beginning of the 5-day dextran sulfate sodium (DSS) treatment to 14 days later. Measurements of colitis indicators (colon weight:length ratio, myeloperoxidase activity, cytokine expressions) showed a similar level of colonic inflammation in both DSS groups during the colitis induction phase. However, during the colitis resolution phase, inflammation intensity was higher in the DSS-HP group than in the DSS-NP group as evidenced by higher inflammatory score and body weight loss. This coincided with a higher mortality rate. In surviving animals, an increase in colonic crypt height associated with a higher number of colon epithelial cells per crypt, and TGF beta3 content was observed in the DSS-HP vs. DSS-NP group. Moreover, colonic expression patterns of tight junction proteins and E-cadherin were also different according to the diet. Altogether, our results indicate that the HP diet, when given during both the induction and resolution periods of DSS-induced colitis, showed deleterious effects during the post-induction phase. However, HP diet ingestion was also associated with morphological and biochemical differences compatible with higher colonic epithelium restoration in surviving animals, indicating an effect of the dietary protein level on colonic crypt repair after acute inflammation. These data highlight the potential impact of the dietary protein amount during the colitis course. PMID- 27562062 TI - Germinal centers and autoimmune disease in humans and mice. AB - Antibodies are involved in the pathogenesis of many autoimmune diseases. Although the mechanisms underlying the antibody response to infection or vaccination are reasonably well understood, we still have a poor understanding of the nature of autoimmune antibody responses. The most well studied are the anti-nuclear antibody responses characteristic of systemic lupus erythematosus and studies over the past decade or so have demonstrated a critical role for signaling by TLR7 and/or TLR9 in B cells to promote these responses. These Toll-like receptors (TLRs) can promote T-cell-independent extrafollicular antibody responses with a heavy-chain class switch and a low degree of somatic mutation, but they can also strongly boost the germinal center response that gives rise to high-affinity antibodies and long-lived plasma cells. TLRs have been shown to enhance affinity maturation in germinal center responses to produce high-affinity neutralizing antibodies in several virus infection models of mice. Although more data are needed, it appears that anti-nuclear antibodies in mouse models of lupus and in lupus patients can be generated by either pathway, provided there are genetic susceptibility alleles that compromise B-cell tolerance at one or another stage. Limited data in other autoimmune diseases suggest that the germinal center response may be the predominant pathway leading to autoantibodies in those diseases. A better understanding of the mechanisms of autoantibody production may ultimately be helpful in the development of targeted therapeutics for lupus or other autoimmune diseases. PMID- 27562065 TI - Dan David Prize: C. A. Mirkin and A. P. Alivisatos / SBIC Early Career Award: G. G. Hartinger / Royal Medal: J. M. Thomas. PMID- 27562063 TI - Immunometabolism and autoimmunity. AB - A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity. Additionally, some autoimmune diseases share alterations in metabolic pathways, key metabolites or metabolic byproducts such as reactive oxygen species. Other examples for metabolic changes in autoimmune settings include modifications in amino acid and cholesterol levels or glucose catabolism. Thus, the emerging field of immunometabolism may hold the potential to discover new therapeutic targets. Here, we discuss recent findings describing metabolic changes in autoimmune arthritis, multiple sclerosis as well as type 1 diabetes, focusing on pathophysiological aspects. PMID- 27562064 TI - Rare phenotypes in the understanding of autoimmunity. AB - The study of rare phenotypes has a long history in the description of autoimmune disorders. First Mendelian syndromes of idiopathic tissue destruction were defined more than 100 years ago and were later revealed to result from immune mediated reactivity against self. In the past two decades, continuous advances in sequencing technology and particularly the advent of next-generation sequencing have allowed to define the genetic basis of an ever-growing number of Mendelian forms of autoimmunity. This has provided unique insight into the molecular pathways that govern immunological homeostasis and that are indispensable for the prevention of self-reactive immune-mediated tissue damage and 'horror autotoxicus'. Here we will discuss selected examples of past and recent investigations into rare phenotypes of autoimmunity that have delineated pathways critical for central and peripheral control of the adaptive immune system. We will outline the implications of these findings for rare and common forms of autoimmunity and will discuss the benefits and potential pitfalls of the integration of next-generation sequencing into algorithms for clinical diagnostics. Because of the concise nature of this review, we will focus on syndromes caused by defects in the control of adaptive immunity as innate immune mediated autoinflammatory disorders have been covered in excellent recent reviews on Mendelian and polygenic forms of autoimmunity. PMID- 27562066 TI - Sex-related differences in reactivity of cerebral arterioles during moderate exercise training. AB - OBJECTIVE: Our goals were to determine the influence of sex on reactivity of cerebral arterioles and whether MExT could influence sex-related differences in reactivity of cerebral arterioles. MATERIALS AND METHODS: Responses of cerebral arterioles were measured in Sed and MExT adult male and female Sprague-Dawley rats to eNOS-dependent (ADP), nNOS-dependent (NMDA), and NOS-independent (nitroglycerin) agonists before and following L-NMMA. In addition, protein expression for eNOS and nNOS was determined. RESULTS: NOS-dependent vasodilation was enhanced in Sed and MExT female rats compared to their male counterparts. L NMMA produced a greater decrease in baseline diameter of arterioles in females compared to males, and produced less inhibition of NOS-dependent vasodilation in females. Expression of eNOS protein was significantly increased in Sed female when compared to Sed male rats; nNOS protein was similar in Sed males and females, but increased in MExT females. CONCLUSIONS: The findings from this study indicate that while NOS-dependent vascular reactivity is increased in females, MExT does not alter vasodilation in males or females. These studies provide insights into the influence of sex and MExT on the cerebral microcirculation and may have implications regarding mechanisms that protect the brain in females compared to males. PMID- 27562067 TI - The effects of different aerobic exercise intensities on serum serotonin concentrations and their association with Stroop task performance: a randomized controlled trial. AB - PURPOSE: Acute exercise improves selective aspects of cognition such as executive functioning. Animal studies suggest that some effects are based on exercise induced alterations in serotonin (5-HT) secretion. This study evaluates the impact of different aerobic exercise intensities on 5-HT serum levels as well as on executive functioning considering 5-HT as a potential mediator. METHODS: 121 young adults (23.8 +/- 3.6 years) were examined in a randomized controlled trial including three exercise intervention (35 min) groups (low intensity, 45 % of the maximal heart rate (HRmax); moderate intensity, 65 % HRmax; high intensity, 85 % HRmax) and one control group. 5-HT levels and response inhibition (measured by a computerized Stroop test) were assessed pre- and post-intervention. RESULTS: There was a significant (p = 0.022) difference between groups regarding serum Delta5-HT levels. Post hoc tests indicated significant (p = 0.013) higher 5-HT serum levels for the high-intensity group compared to the control group while other groups did not differ significantly from each other. Serum Delta5-HT levels and exercise intensity were shown to be linearly associated through polynomial contrast analysis (p = 0.003). Furthermore, ANOVA revealed a significant difference for Stroop parameter reading (p = 0.030) and a tendency for reverse Stroop effect (p = 0.061). Correlation analysis showed that augmented 5-HT levels were associated with improved results in response inhibition. CONCLUSIONS: This study indicates that intensive acute exercise increases serum 5-HT levels compared to a control group. These findings might be relevant for many other related research fields in exercise science, since 5-HT receptors are expressed on many different cell types including endothelia and immune cells. PMID- 27562068 TI - TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. AB - TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1-Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17-Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy. PMID- 27562069 TI - C. elegans midbodies are released, phagocytosed and undergo LC3-dependent degradation independent of macroautophagy. AB - In animals, the midbody coordinates the end of cytokinesis when daughter cells separate through abscission. The midbody was thought to be sequestered by macroautophagy, but recent evidence suggests that midbodies are primarily released and phagocytosed. It was unknown, however, whether autophagy proteins play a role in midbody phagosome degradation. Using a protein degradation assay, we show that midbodies are released in Caenorhabditis elegans Released midbodies are known to be internalized by actin-driven phagocytosis, which we show requires the RAB-5 GTPase to localize the class III phosphoinositide 3-kinase (PI3K) complex at the cortex. Autophagy-associated proteins, including the Beclin 1 homolog BEC-1 and the Atg8/LC3-family members LGG-1 and LGG-2, localize around the midbody phagosome and are required for midbody degradation. In contrast, proteins required specifically for macroautophagy, such as UNC-51 and EPG-8 (homologous to ULK1/Atg1 and Atg14, respectively) are not required for midbody degradation. These data suggest that the C. elegans midbody is degraded by LC3 associated phagocytosis (LAP), not macroautophagy. Our findings reconcile the two prevailing models on the role of phagocytic and autophagy proteins, establishing a new non-canonical role for autophagy proteins in midbody degradation. PMID- 27562070 TI - Triadin and CLIMP-63 form a link between triads and microtubules in muscle cells. AB - In skeletal muscle, the triad is a structure comprising a transverse (T)-tubule and sarcoplasmic reticulum (SR) cisternae. Triads constitute the basis of excitation-contraction coupling as the cradle of the Ca2+ release complex. We have shown previously that triadin, a member of this complex, has shaping properties on reticulum membrane and is indirectly involved in a link between triads and microtubules. We have identified here that CLIMP-63 (also known as CKAP4), as the partner of triadin, is responsible for this association of triads and microtubules. Triadin and CLIMP-63 interact through their respective luminal domains and the shaping properties of triadin depend on the capacity of CLIMP-63 to bind microtubules with its cytosolic portion. In skeletal muscle, CLIMP-63 is localized in the SR, including triads, and is associated with the Ca2+ release complex through its interaction with triadin. Knockout of triadin in muscles results in the delocalization of CLIMP-63 from triads, its dissociation from the Ca2+ release complex and a disorganization of the microtubule network. Our results suggest that the association of triadin and CLIMP-63 could be involved in the shaping of SR terminal cisternae and in the guidance of microtubules close to the triads. PMID- 27562073 TI - Language processing is not a race against time. AB - We agree with Christiansen & Chater (C&C) that language processing and acquisition are tightly constrained by the limits of sensory and memory systems. However, the human brain supports a range of cognitive functions that mitigate the effects of information processing bottlenecks. The language system is partly organised around these moderating factors, not just around restrictions on storage and computation. PMID- 27562072 TI - Determinants of timely initiation of complementary feeding among mothers with children aged 6-23 months in Lalibela District, Northeast Ethiopia, 2015. AB - BACKGROUND: Optimal complementary feeding alone prevents six percent of child mortality, but it has continued to be considered as sub-optimal in Ethiopia. Therefore, this study aimed to assess timely initiation of complementary feeding and associated factors among mothers with children aged 6-23 months in Lalibela District. METHODS: A community-based cross-sectional study was conducted from March 01 to April 29, 2015. Four hundred twenty-one mother-child pairs were selected by the systematic random sampling technique. An interviewer-administered questionnaire was used to collect data. A multivariable logistic regression analysis was employed to identify factors associated with timely initiation of complementary feeding. The Adjusted Odds Ratio (AOR) with a 95 % Confidence Interval (CI) was computed to assess the strength of association, and variables with a P-value of <0.05 were considered as statistically significant in the multivariable analysis. RESULTS: The study demonstrated that, the prevalence of timely initiation of complementary feeding was 63 %. In addition, mother's education [AOR = 4.33, 95 % CI: 1.99, 9.40], antenatal care follow up [AOR = 5.90, 95 % CI: 2.45, 14.21], and institutional delivery [AOR = 2.54, 95 % CI: 1.33, 4.82] were found key determinants of timely initiation of complementary feeding. CONCLUSION: In this community, timely initiation of complementary feeding was lower than the World Health Organization cut-off point for good practice of complementary feeding. Therefore, intensifying utilization of antenatal care and institutional delivery helps to improve the coverage of timely initiation of complementary feeding. Furthermore, the focus needs to be on uneducated women. PMID- 27562074 TI - In Infants' Hands: Identification of Preverbal Infants at Risk for Primary Language Delay. AB - Early identification of primary language delay is crucial to implement effective prevention programs. Available screening instruments are based on parents' reports and have only insufficient predictive validity. This study employed observational measures of preverbal infants' gestural communication to test its predictive validity for identifying later language delays. Pointing behavior of fifty-nine 12-month-old infants was analyzed and related to their language skills 1 year later. Results confirm predictive validity of preverbal communication for language skills with the hand shape of pointing being superior compared to the underlying motives for pointing (imperative vs. declarative). Twelve-month-olds who pointed only with their open hand but never with their index finger were at risk for primary language delay at 2 years of age. PMID- 27562071 TI - Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes. AB - Meiotic oocytes lack classic centrosomes and, therefore, bipolar spindle assembly depends on clustering of acentriolar microtubule-organizing centers (MTOCs) into two poles. However, the molecular mechanism regulating MTOC assembly into two poles is not fully understood. The kinase haspin (also known as GSG2) is required to regulate Aurora kinase C (AURKC) localization at chromosomes during meiosis I. Here, we show that inhibition of haspin perturbed MTOC clustering into two poles and the stability of the clustered MTOCs. Furthermore, we show that AURKC localizes to MTOCs in mouse oocytes. Inhibition of haspin perturbed the localization of AURKC at MTOCs, and overexpression of AURKC rescued the MTOC clustering defects in haspin-inhibited oocytes. Taken together, our data uncover a role for haspin as a regulator of bipolar spindle assembly by regulating AURKC function at acentriolar MTOCs in oocytes. PMID- 27562076 TI - The burden of proof for a cultural group selection account. AB - Richerson et al. establish cultural group selection as a plausible force in human social evolution. However, they do not demonstrate its causal precedence for any trait, let alone its "essentialness." To do so, they must show that a particular group trait was caused by cultural transmission, and directly caused differences in group fitness. PMID- 27562077 TI - Epidemiology of bleeding symptoms and hypermobile Ehlers-Danlos syndrome in paediatrics. PMID- 27562075 TI - Glucosamine sulfate suppresses the expression of matrix metalloproteinase-3 in osteosarcoma cells in vitro. AB - BACKGROUND: Glucosamine, a common dietary supplement, has a possible anti-sarcoma effect. However, an understanding of the underlying mechanism of such an effect is limited. For this study we hypothesized that glucosamine suppresses the basal level of matrix metalloproteinase expression in human osteosarcoma cell lines. METHODS: We examined the osteosarcoma cell lines, MG-63 and SaOS-2. Cells were exposed to 0, 10, 50 and 100 MUg/ml glucosamine sulfate for 48 h and treatment toxicity was determined through measurement of cell viability and proliferation. Relative gene expression of matrix metalloproteinase (MMP)-2, -3 and -9 was quantified by real-time polymerase chain reaction. Protein levels of MMP-2 and -9 were assessed by ELISA. RESULTS: Administration of 10, 50 or 100 MUg/ml glucosamine sulfate had no effect on the cell viability of MG-63 and SaOS-2 cells. A significant reduction of MMP expression in both cell lines was observed only for MMP-3, while a decrease in MMP-9 was seen in SaOS-2 cells. The expression of MMP-2 was not significantly affected in either cell line. Protein level of MMP-3 was reduced in both cell lines upon stimulation with 10 MUg/ml glucosamine sulfate whereas for MMP-9 a decrease could only be observed in SaOS-2 cells. CONCLUSION: In this study, we found a pronounced suppressive effect of glucosamine sulfate particularly on MMP-3 and also MMP-9 mRNA and protein levels in osteosarcoma cell lines in vitro. The data warrants further investigations into the potential anti-tumor efficacy of glucosamine sulfate in osteosarcoma. PMID- 27562079 TI - Precision Continuous Renal Replacement Therapy and Solute Control. AB - Continuous renal replacement therapy (CRRT) remains the dominant form of renal support among critically ill patients worldwide. Current clinical practice on CRRT prescription mostly relies on high quality studies suggesting no impact of CRRT dose on critically ill patients' outcomes. Recent clinical practice guidelines have been developed based on these studies recommending a static prescribed CRRT dose of 20-25 ml/kg/h. There is a rationale for renewed attention to CRRT prescription/practice based on the concept of dynamic solute control adapted to the changing clinical needs of critically ill patients. In response, Acute Disease Quality Initiative convened a 17th consensus meeting centered on re evaluation of CRRT. This work group developed 4 themes focused specifically on CRRT dose prescription, delivery and solute control that were summarized in a series of consensus statements, along with the identification of critical knowledge gaps. CRRT dose prescription and delivery can be based on effluent flow rate. Delivered dose should be routinely monitored to ensure coherence with prescribed dose. CRRT dose should be dynamic, in recognition of between- and within-patient variation in targeted solute control or unintended solute clearance. Quality measures specific for monitoring delivered CRRT dose have been proposed that require further validation, prior to implementation, into the practice of guiding optimal CRRT dosage. PMID- 27562080 TI - Differentiation of individual selves facilitates group-level benefits of ultrasociality. AB - Gowdy & Krall's target article complements our recent theorizing on group behavior. In our comment, we elucidate complementary aspects of the two theories and highlight the importance of differentiation of selves for human groups to reap the benefits of ultrasociality. We propose that achieving optimal group outcomes depends on the differentiation of individual selves. PMID- 27562081 TI - Sequence and phylogenetic analysis of the complete mitochondrial genome of Lasiopodomys mandarinus mandarinus (Arvicolinae, Rodentia). AB - Mandarin vole (Lasiopodomys mandarinus) is a subterranean rodent that is often used as a model for studying subterranean hypoxic stress in mammals. However the taxonomy of this species is still in dispute. Mitochondrial DNA (mtDNA) has long been used for phylogenetic reconstruction and, in this study, the complete mitochondrial genome of L. mandarinus mandarinus was sequenced. Our results showed that the mitochondrial genome of L. m. mandarinus is a circular molecule of 16,367bp, which contains 13 protein-coding genes, 22 tRNA and 2 rRNA genes. Except for the 8 tRNA and ND6 genes, all other mitochondrial genes are encoded on the heavy strand. We also analyzed the phylogenetic position of L. mandarinus in respect to the tribe Arvicolini using the sequence of complete Cytb gene, 2rRNA genes and 12 protein-coding genes, and maximum likelihood and Bayesian methods. Our results gave further support to the species status of L. mandarinus and the generic status of Lasiopodomys. PMID- 27562078 TI - Improvement of Bacillus subtilis for poly-gamma-glutamic acid production by genome shuffling. AB - Poly-gamma-glutamic acid (gamma-PGA) is a promising microbial polymer with potential applications in industry, agriculture and medicine. The use of high gamma-PGA-producing strains is an effective approach to improve productivity of gamma-PGA. In this study, we developed a mutant, F3-178, from Bacillus subtilis GXA-28 using genome shuffling. The morphological characteristics of F3-178 and GXA-28 were not identical. Compared with GXA-28 (18.4 +/- 0.8 g l-1 ), the yield of gamma-PGA was 1.9-fold higher in F3-178 (34.3 +/- 1.2 g l-1 ). Results from batch fermentation in 3.7 l fermenter showed that F3-178 was satisfactory for industrial production of gamma-PGA. Metabolic studies suggested that the higher gamma-PGA yield in F3-178 could be attributed to increased intracellular flux and uptake of extracellular glutamate. Real-time PCR indicated that mRNA level of pgsB in F3-178 was 18.8-fold higher than in GXA-28, suggesting the higher yield might be related to the overexpression of genes involved in gamma-PGA production. This study demonstrated that genome shuffling can be used for rapid improvement of gamma-PGA strains, and the possible mechanism for the improved phenotype was also explored at the metabolic and transcriptional levels. PMID- 27562082 TI - Association of oxidative stress gene polymorphisms with presbycusis. AB - INTRODUCTION: Presbycusis is characterised by etiopathological changes in the cochlea of the inner ear due to genetic and environmental factors and has a serious impact on quality of life. The present study was aimed to evaluate the role of oxidant stress gene polymorphisms in the development of presbycusis. SUBJECTS AND METHODS: 220 subjects with confirmed presbycusis from ENT specialists of MAA ENT hospital, Hyderabad, India from 2012 to 2014 were considered for the study. 270 age and sex matched controls were included in the study. Analysis of gene polymorphisms of SNPs cytochrome P450 1A1 (CYP1A1) 3801 T>C, 2455 A>G and 2453 A>C; glutathione S transferase (GST) T1 and M1; N-acetyl transferase (NAT2) 282 C>T and 857 G>A; uncoupled proteins (UCP1) (-3826) A>G and (UCP2) (866)G>A was carried out. Variations in the allelic and genotypic frequencies obtained were computed and analysed using appropriate statistical methods. RESULTS: The results of the study indicated that CYP1A1 gene polymorphism at 2453 C>A (adjusted OR: 1.59, 95% CI: 1.01-2.87) and 2455 A>G (adjusted OR: 1.87, 95% CI: 1.07-3.37), double null genotype of GSTM1 and GSTT1 (adjusted OR: 8.88, 95% CI: 4.10-19.19), NAT2 gene at C282T (adjusted OR: 1.77, 95% CI: 1.02-3.11) and G590 A (adjusted OR: 1.83, 95% CI 1.20-3.63) and UCP2 ( 866) G>A (adjusted OR: 12.39; 95% CI: 6.51-23.56) showed increased risk for presbycusis while CYP1A1 at 3801 T>C and UCP1 (-3286) A>G exhibited no association. The haplotype combinations of T-G-A of CYP1A1 at 3801, 2455 and 2453 positions as well as T-A of NAT2*6 at 282 and 590 positions were found to contribute significant risk for the onset of presbycusis. CONCLUSIONS: Gene polymorphisms of CYP1A1 (A2455G, C2453A), NAT2*6 (C282T, G590 A), GST T1/M1 (double null genotype) and UCP2 (G-866 A) were found to contribute significant risk to presbycusis. PMID- 27562083 TI - Sequence analyses and chromosomal distribution of the Tc1/Mariner element in Parodontidae fish (Teleostei: Characiformes). AB - Transposable elements are able to move along eukaryotic genomes. They are divided into two classes according to their transposition intermediate: RNA (class I or retrotransposons) or DNA (class II or DNA transposons). Most of these sequences are inactive or non-autonomous in eukaryotic genomes. Inactivate transposons can accumulate mutations at neutral rates until losing their molecular identity. They may either be eliminated from the genome or take on different molecular functions. Transposable elements may also participate in the differentiation of sex chromosomes. Therefore, the structural variations and nucleotide similarity of Tc1/Mariner sequences were analyzed along with their potential participation in the differentiation processes of sex chromosomes in the genomes of Parodontidae fish. All Parodontidae species presented non-autonomous copies of Tc1/Mariner with structural variation, different levels of deterioration (genetic distance), and variations in insertion and deletion patterns. The physical mapping of Tc1/Mariner on chromosomes revealed dispersed signals in euchromatins, with small accumulations in terminal regions and in the sex chromosomes. The gene dosage ratios indicated copy number variations of Tc1/Mariner among the genomes and high transposase open reading frame deterioration in Parodon hilarii and Parodon pongoensis genomes. This transposon presented transcriptional activity in gonads, but there was no significant difference between sexes. This may indicate non-functional protein expression or may correspond to DNA binding proteins derived from Tc1/Mariner. Thus, our results show Tc1/Mariner inactivation along with a diversity in Parodontidae genomes and its participation in the differentiation of the W sex chromosome. PMID- 27562084 TI - Power law incidence rate in epidemic models: Comment on: "Mathematical models to characterize early epidemic growth: A review" by Gerardo Chowell et al. PMID- 27562085 TI - A general theory of early growth?: Comment on: "Mathematical models to characterize early epidemic growth: A review" by Gerardo Chowell et al. PMID- 27562086 TI - How do biting disease vectors behaviourally respond to host availability? AB - BACKGROUND: Ecological theory predicts a diverse range of functional responses of species to resource availability; but in the context of human blood consumption by disease vectors, a simplistic, linear response is ubiquitously assumed. A simple and flexible model formulation is presented that extends the Holling's Types to account for a wider range of qualitatively distinct behaviours, and used to examine the impact of different vector responses to the relative availability of multiple blood-host species. RESULTS: Epidemiological models of falciparum malaria, Chagas disease and Lyme disease demonstrate that the standard, often implicit, assumption of a linear functional response can lead to spurious under- or over-estimates in disease transmission potential, across a full range of pathogen life-cycles. It is shown how the functional response in vector biting can augment disease intervention outcomes. Interactions between vector biting behaviour and uneven pathogen transmission probabilities between alternative hosts, as is the case for Chagas disease, can render infection more resilient to control. CONCLUSIONS: Both the novel response formula and the nested vector-borne disease structure offer a flexible framework that can be applied to other vector borne diseases in assessing the role of this newly identified aspect of biting behavioural ecology. PMID- 27562087 TI - Mechanisms for interaction: Syntax as procedures for online interactive meaning building. AB - We argue that to reflect participant interactivity in conversational dialogue, the Christiansen & Chater (C&C) perspective needs a formal grammar framework capturing word-by-word incrementality, as in Dynamic Syntax, in which syntax is the incremental building of semantic representations reflecting real-time parsing dynamics. We demonstrate that, with such formulation, syntactic, semantic, and morpho-syntactic dependencies are all analysable as grounded in their potential for interaction. PMID- 27562088 TI - 6-Shogaol, an active compound of ginger, alleviates allergic dermatitis-like skin lesions via cytokine inhibition by activating the Nrf2 pathway. AB - Allergic dermatitis (AD) clinically presents with skin erythematous plaques, eruption, and elevated serum IgE, and T helper cell type 2 and 1 (Th2 and Th1) cytokine levels. 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown anti-inflammatory effects, but its inhibitory effects on AD are unknown. The aim of this study was to examine whether 6-shogaol inhibits AD-like skin lesions and their underlying mechanism in vivo and in vitro. An AD-like response was induced by tumor necrosis factor-alpha (TNF-alpha)+IFN-gamma in human keratinocytes or by 2,4-dinitrochlorobenzene (DNCB) in mice. In vivo, 6-shogaol inhibited the development of DNCB-induced AD like skin lesions and scratching behavior, and showed significant reduction in Th2/1-mediated inflammatory cytokines, IgE, TNF-alpha, IFN-gamma, thymus and activation-regulated chemokine, IL-1, 4, 12, and 13, cyclooxygenase-2, and nitric oxide synthase levels. In vitro, 6-shogaol inhibited reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling, and increased the levels of total glutathione, heme oxygenase-1, and quinone 1 via nuclear factor erythroid 2 related factor 2 (Nrf2) activation. 6-Shogaol can alleviate AD-like skin lesions by inhibiting immune mediators via regulating the ROS/MAPKs/Nrf2 signaling pathway, and may be an effective alternative therapy for AD. PMID- 27562089 TI - Brazilian attorneys demand abortion rights for women infected with Zika. PMID- 27562090 TI - Achieving 90% Adoption of Clinical Practice Guidelines Using the Delphi Consensus Method in a Large Orthopedic Group. AB - BACKGROUND: Little is known about the implementation rate of clinical practice guidelines (CPGs). Our purpose was to report on the adoption rate of CPGs created and implemented by a large orthopedic group using the Delphi consensus method. METHODS: The draft CPGs were created before the group's annual meeting by 5 teams each assigned a subset of topics. The draft guidelines included a statement and a summary of the available evidence. Each guideline was debated in both small-group and plenary sessions. Voting was anonymous and a 75% supermajority was required for passage. A Likert scale was used to survey the patient's experience with the process at 1 week, and the Kirkpatrick evaluation model was used to gauge the efficacy of the process over a 6-month time frame. RESULTS: Eighty-five orthopedic surgeons attended the meeting. Fifteen guidelines grouped into 5 topics were created. All passed. Eighty-six percent of attendees found the process effective and 84% felt that participating in the process made it more likely that they would adopt the guidelines. At 1 week, an average of 62% of attendees stated they were practicing the guideline as written (range: 35%-72%), and at 6 months, 96% stated they were practicing them (range: 82%-100%). CONCLUSION: We have demonstrated that a modified Delphi method for reaching consensus can be very effective in both creating CPGs and leading to their adoption. Further we have shown that the process is well received by participants and that an inclusionary approach can be highly successful. PMID- 27562091 TI - Primary Total Knee Arthroplasty After Solid Organ Transplant: Survivorship and Complications. AB - BACKGROUND: Clinical outcomes remain largely unknown beyond perioperative and short-term follow-up of solid organ transplant (SOT) patients undergoing total knee arthroplasty (TKA). METHODS: Patient mortality, implant survivorship, and complications of 96 TKAs (76 patients) after SOT were retrospectively reviewed through an internal joint registry. Mean age at index arthroplasty was 66 years, and mean follow-up was 4 years. RESULTS: Overall mortality rates at 1 year, 2 years, and 5 years from TKA were 2.6%, 7.9%, and 13.2%, respectively, and combined SOT patient survivorship was 92% at 2 years and 82% at 5 years. Implant survivorship free of any component revision or implant removal was 98% at 2 years and 93% at 5 years. There was a high rate of perioperative complications (12.5%), including periprosthetic fractures (5.2%) and deep periprosthetic infection (3.2%). CONCLUSION: TKA does not appear to have any effect on SOT patient survivorship following the procedure. However, SOT patients may have a higher risk of perioperative complications and a lower implant survivorship than the general population of TKA patients at midterm follow-up. PMID- 27562092 TI - Lessons Learned During 48 Years of Orthopedic Practice. PMID- 27562093 TI - Inactivated coxsackievirus A10 experimental vaccines protect mice against lethal viral challenge. AB - Coxsackievirus A10 (CVA10) has become one of the major causative agents of hand, foot and mouth disease (HFMD). It is now recognized that CVA10 should be targeted for vaccine development. We report here that beta-propiolactone inactivated whole virus based CVA10 vaccines can elicit protective immunity in mice. We prepared two inactivated CVA10 experimental vaccines derived from the prototype strain CVA10/Kowalik and from a clinical isolate CVA10/S0148b, respectively. Immunization with the experimental vaccines elicited CVA10-specific serum antibodies in mice. The antisera from vaccinated mice could potently neutralize in vitro infection with either homologous or heterologous CVA10 strains. Importantly, passive transfer of the anti-CVA10 sera protected recipient mice against CVA10/Kowalik or CVA10/S0148b infections. Moreover, active immunization with the inactivated vaccines also conferred protection against homologous and heterologous infections in mice. Collectively, our results demonstrate the proof of-concept for inactivated whole-virus based CVA10 vaccines. PMID- 27562095 TI - A comparative historical and demographic study of the neuromodulation management techniques of deep brain stimulation for dystonia and cochlear implantation for sensorineural deafness in children. AB - : Cochlear implants for sensorineural deafness in children is one of the most successful neuromodulation techniques known to relieve early chronic neurodisability, improving activity and participation. In 2012 there were 324,000 recipients of cochlear implants globally. AIM: To compare cochlear implant (CI) neuromodulation with deep brain stimulation (DBS) for dystonia in childhood and explore relations between age and duration of symptoms at implantation and outcome. METHODS: Comparison of published annual UK CI figures for 1985-2009 with a retrospective cohort of the first 9 years of DBS for dystonia in children at a single-site Functional Neurosurgery unit from 2006 to 14. RESULTS: From 2006 to 14, DBS neuromodulation of childhood dystonia increased by a factor of 3.8 to a total of 126 cases over the first 9 years, similar to the growth in cochlear implants which increased by a factor of 4.1 over a similar period in the 1980s rising to 527 children in 2009. The CI saw a dramatic shift in practice from implantation at >5 years of age at the start of the programme towards earlier implantation by the mid-1990s. Best language results were seen for implantation <5 years of age and duration of cochlear neuromodulation >4 years, hence implantation <1 year of age, indicating that severely deaf, pre-lingual children could benefit from cochlear neuromodulation if implanted early. Similar to initial CI use, the majority of children receiving DBS for dystonia in the first 9 years were 5-15 years of age, when the proportion of life lived with dystonia exceeds 90% thus limiting benefits. CONCLUSION: Early DBS neuromodulation for acquired motor disorders should be explored to maximise the benefits of dystonia reduction in a period of maximal developmental plasticity before the onset of disability. Learning from cochlear implantation, DBS can become an accepted management option in children under the age of 5 years who have a reduced proportion of life lived with dystonia, and not viewed as a last resort reserved for only the most severe cases where benefits may be at their most limited. PMID- 27562094 TI - TNF-alpha induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice. AB - BACKGROUND: High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-alpha, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-alpha, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-alpha mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined. METHODS: Mesenteric vascular beds were isolated from C57Bl/6J and TNF-alpha KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-alpha and PTEN contribute to vascular dysfunction. RESULTS: Vasodilation in response to insulin was decreased in HFD fed mice and in ex vivo control arteries incubated with TNF-alpha. TNF-alpha receptors deficiency and TNF-alpha blockade with infliximab abolished the effects of HFD and TNF-alpha on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-alpha receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice. CONCLUSION: TNF-alpha induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-alpha and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity related conditions. PMID- 27562096 TI - Treatment of autistic spectrum disorder with insulin-like growth factors. AB - There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD like behavior defects. The molecular basis for a cerebellar contribution has been demonstrated in a mouse model. These have led to a potential mechanism-based use of drug targets and mouse models. Neurotrophic factors are potential candidates for the treatment. Insulin-like growth factor-1 (IGF-1) is altered in autism. It reduces neuro-inflammation: by causing changes of cytokines such as IL-6 and microglial function. IGF-1 reduces the defects in the synapse. It alleviates NMDA induced neurotoxicity via the IGF-AKT-mTor pathway in microglia. IGF-1 may rescue function in Rett syndrome and ASD caused by changes of the SCHANK3 gene. There are recently pilot studies of the treatment of Rett syndrome and of SCHANK3 gene deficiency syndromes. The FDA has granted Orphan drug designations for Fragile X syndrome, SCHANK3 gene deficiency syndrome and Rett syndrome. PMID- 27562097 TI - Stroke-like episodes, peri-episodic seizures, and MELAS mutations. AB - PURPOSE: Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC hyperintensity) or partial cytotoxic oedema (DWI hyperintensity, ADC hypointensity) in the acute and subacute stage, and with gyriform T1 hyperintensity (cortical necrosis) in the chronic stage. PRINCIPAL RESULTS: SLEs must be clearly distinguished from ischaemic stroke, since management of these two entities is different. SLEs may go along with or without seizures or epileptiform discharges on EEG. However, in MELAS syndrome seizures may also occur in the absence of SLEs. Focal and generalised seizures have been reported but it is currently unknown if the one or the other prevail. SLEs with and without seizures may respond to NO-precursors l-arginine, succinate, or citrulline. As a supportive measure a ketogenic diet should be initiated. Seizures prior to or during a SLE or paroxysmal EEG-activity during a SLE should be initially treated with antiepileptic drugs (AEDs) with low mitochondrion toxicity. Only in case these AEDs are ineffective, AEDs with higher mitochondrion toxicity should be added. MAJOR CONCLUSIONS: All patients with SLEs need to have an EEG recorded irrespective if they have manifesting seizures or not. There are no mtDNA or nDNA mutations which predispose for SLEs with seizures. PMID- 27562098 TI - Long-term safety and effectiveness of pramipexole in tetrahydrobiopterin deficiency. AB - Tetrahydrobiopterin (BH4) deficiencies are inherited neuro-metabolic disorders leading to monoamine neurotransmitters deficiency. An individualized replacement therapy with neurotransmitters precursors is necessary to restore dopaminergic and serotoninergic homeostasis. The correction of dopaminergic tone is complicated, like in Parkinson disease, by l-dopa short half-life and adverse effects. To improve this picture, since 2009 we introduced the non-ergot dopamine agonist pramipexole as an adjunct to l-dopa therapy in the treatment of the most common causes of BH4 deficiency, 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and dihydropteridine reductase (DHPR) deficiency. In the short-term period, this approach allowed substantial clinical advantages in affected patients, with amelioration and stabilization of the clinical picture on twice daily treatment administration and no adverse effect. Here we describe the long term clinical follow-up (83 +/- 24 months) of seven patients with BH4 deficiency treated with pramipexole. After a period of good clinical compensation (34 +/- 1 months), different impulse control disorders (gambling, compulsive buying, and hypersexuality) were observed in three patients treated with high-dose pramipexole (0.030-0.033 mg/kg/day) beyond adolescence. These psychiatric adverse effects promptly disappeared after curtailing pramipexole dose by 50-60%. Low dose pramipexole therapy has been safe and effective in the long-term period in all treated patients (59 +/- 9 months). High-dose pramipexole therapy in BH4 deficiency can be complicated, like in Parkinson disease, by psychiatric adverse effects. Low-dose pramipexole therapy (~0.010 mg/kg/day) has been safe and clinically effective on long-term follow-up, representing a helpful therapeutic option in patients with BH4 deficiency. PMID- 27562099 TI - Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish. AB - Alcoholic liver disease (ALD) results from alcohol overconsumption and is among the leading causes of liver-related morbidity and mortality worldwide. Elevated expression of vascular endothelial growth factor (VEGF) and its receptors has been observed in ALD, but how it contributes to ALD pathophysiology is unclear. Here, we investigated the impact of VEGF signaling inhibition on an established zebrafish model of acute alcoholic liver injury. Kdrl activity was blocked by chemical inhibitor treatment or by genetic mutation. Exposing 4-day-old zebrafish larvae to 2% ethanol for 24 h induced hepatic steatosis, angiogenesis and fibrogenesis. The liver started self-repair once ethanol was removed. Although inhibiting Kdrl did not block the initial activation of hepatic stellate cells during ethanol treatment, it suppressed their proliferation, extracellular matrix protein deposition and fibrogenic gene expression after ethanol exposure, thus enhancing the liver repair. It also ameliorated hepatic steatosis and attenuated hepatic angiogenesis that accelerated after the ethanol treatment. qPCR showed that hepatic stellate cells are the first liver cell type to increase the expression of VEGF ligand and receptor genes in response to ethanol exposure. Both hepatic stellate cells and endothelial cells, but not hepatic parenchymal cells, expressed kdrl upon ethanol exposure and were likely the direct targets of Kdrl inhibition. Ethanol-induced steatosis and fibrogenesis still occurred in cloche mutants that have hepatic stellate cells but lack hepatic endothelial cells, and Kdrl inhibition suppressed both phenotypes in the mutants. These results suggest that VEGF signaling mediates interactions between activated hepatic stellate cells and hepatocytes that lead to steatosis. Our study demonstrates the involvement of VEGF signaling in regulating sustained liver injuries after acute alcohol exposure. It also provides a proof of principle of using the zebrafish model to identify molecular targets for developing ALD therapies. PMID- 27562100 TI - Acute and long-term outcomes in a Drosophila melanogaster model of classic galactosemia occur independently of galactose-1-phosphate accumulation. AB - Classic galactosemia (CG) is a potentially lethal inborn error of metabolism that results from the profound loss of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme in the Leloir pathway of galactose metabolism. Neonatal detection and dietary restriction of galactose minimizes or resolves the acute sequelae of CG, but fails to prevent the long-term complications experienced by a majority of patients. One of the substrates of GALT, galactose-1-phosphate (Gal 1P), accumulates to high levels in affected infants, especially following milk exposure, and has been proposed as the key mediator of acute and long-term pathophysiology in CG. However, studies of treated patients demonstrate no association between red blood cell Gal-1P level and long-term outcome severity. Here, we used genetic, epigenetic and environmental manipulations of a Drosophila melanogaster model of CG to test the role of Gal-1P as a candidate mediator of outcome in GALT deficiency. Specifically, we both deleted and knocked down the gene encoding galactokinase (GALK) in control and GALT-null Drosophila, and assessed the acute and long-term outcomes of the resulting animals in the presence and absence of dietary galactose. GALK is the first enzyme in the Leloir pathway of galactose metabolism and is responsible for generating Gal-1P in humans and Drosophila Our data confirmed that, as expected, loss of GALK lowered or eliminated Gal-1P accumulation in GALT-null animals. However, we saw no concomitant rescue of larval survival or adult climbing or fecundity phenotypes. Instead, we saw that loss of GALK itself was not benign and in some cases phenocopied or exacerbated the outcome seen in GALT-null animals. These findings strongly contradict the long-standing hypothesis that Gal-1P alone underlies pathophysiology of acute and long-term outcomes in GALT-null Drosophila and suggests that other metabolite(s) of galactose, and/or other pathogenic factors, might be involved. PMID- 27562102 TI - Eye-tracking the time-course of novel word learning and lexical competition in adults and children. AB - Lexical competition is a hallmark of proficient, automatic word recognition. Previous research suggests that there is a delay before a new spoken word becomes engaged in this process, with sleep playing an important role. However, data from one method - the visual world paradigm - consistently show competition without a delay. We trained 42 adults and 40 children (aged 7-8) on novel word-object pairings, and employed this paradigm to measure the time-course of lexical competition. Fixations to novel objects upon hearing existing words (e.g., looks to the novel object biscal upon hearing "click on the biscuit") were compared to fixations on untrained objects. Novel word-object pairings learned immediately before testing and those learned the previous day exhibited significant competition effects, with stronger competition for the previous day pairings for children but not adults. Crucially, this competition effect was significantly smaller for novel than existing competitors (e.g., looks to candy upon hearing "click on the candle"), suggesting that novel items may not compete for recognition like fully-fledged lexical items, even after 24h. Explicit memory (cued recall) was superior for words learned the day before testing, particularly for children; this effect (but not the lexical competition effects) correlated with sleep-spindle density. Together, the results suggest that different aspects of new word learning follow different time courses: visual world competition effects can emerge swiftly, but are qualitatively different from those observed with established words, and are less reliant upon sleep. Furthermore, the findings fit with the view that word learning earlier in development is boosted by sleep to a greater degree. PMID- 27562101 TI - Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice. AB - Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte--specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus. PMID- 27562103 TI - Differences in erect sitting and natural sitting spinal alignment-insights into a new paradigm and implications in deformity correction. AB - BACKGROUND CONTEXT: Sitting spinal alignment is increasingly recognized as a factor influencing strategy for deformity correction. Considering that most individuals sit for longer hours in a "slumped" rather than in an erect posture, greater understanding of the natural sitting posture is warranted. PURPOSE: This study aimed to investigate the differences in sagittal spinal alignment between two common sitting postures: a natural, patient-preferred posture; and an erect, investigator-controlled posture that is commonly used in alignment studies. DESIGN/SETTING: This is a randomized, prospective study of 28 young, healthy patients seen in a tertiary hospital over a 6-month period. PATIENT SAMPLE: Twenty-eight patients (24 men, 4 women), with a mean age of 24 years (range 19 38), were recruited for this study. All patients with first episode of lower back pain of less than 3 months' duration were included. The exclusion criteria consisted of previous spinal surgery, radicular symptoms, red flag symptoms, previous spinal trauma, obvious spinal deformity on forward bending test, significant personal or family history of malignancy, and current pregnancy. OUTCOME MEASURES: Radiographic measurements included sagittal vertical axis (SVA), lumbar lordosis (LL), thoracolumbar angle (TL), thoracic kyphosis (TK), and cervical lordosis (CL). Standard spinopelvic parameters (pelvic incidence, pelvic tilt [PT], and sacral slope) and sagittal apex and end vertebrae were also measured. METHODS: Basic patient demographics (age, gender, ethnicity) were recorded. Lateral sitting whole spine radiographs were obtained using a slot scanner in the imposed erect and the natural sitting posture. Statistical analyses of the radiographical parameters were performed comparing the two sitting postures using chi-squared tests for categorical variables and paired t tests for continuous variables. RESULTS: There was forward SVA shift between the two sitting postures by a mean of 2.9 cm (p<.001). There was a significant increase in CL by a mean of 11.62 degrees (p<.001), and TL kyphosis by a mean of 11.48 degrees (p<.001), as well as a loss of LL by a mean of 21.26 degrees (p<.001). The mean PT increased by 17.68 degrees (p<.001). The entire thoracic and lumbar spine has the tendency to form a single C-shaped curve with the apex moving to L1 (p=.002) vertebra in the majority of patients. CONCLUSIONS: In a natural sitting posture, the lumbar spine becomes kyphotic and contributes to a single C-shaped sagittal profile comprising the thoracic and the lumbar spine. This is associated with an increase in CL and PT, as well as a constant SVA. These findings lend insight into the body's natural way of energy conservation using the posterior ligamentous tension band while achieving sitting spinal sagittal balance. It also provides information on one of the possible causes of proximal junctional kyphosis or proximal junctional failure. PMID- 27562104 TI - The use and reliability of SymNose for quantitative measurement of the nose and lip in unilateral cleft lip and palate patients. AB - INTRODUCTION: It is essential to have a reliable assessment method in order to compare the results of cleft lip and palate surgery. In this study the computer based program SymNose, a method for quantitative assessment of the nose and lip, will be assessed on usability and reliability. METHODS: The symmetry of the nose and lip was measured twice in 50 six-year-old complete and incomplete unilateral cleft lip and palate patients by four observers. For the frontal view the asymmetry level of the nose and upper lip were evaluated and for the basal view the asymmetry level of the nose and nostrils were evaluated. RESULTS: A mean inter-observer reliability when tracing each image once or twice was 0.70 and 0.75, respectively. Tracing the photographs with 2 observers and 4 observers gave a mean inter-observer score of 0.86 and 0.92, respectively. The mean intra observer reliability varied between 0.80 and 0.84. CONCLUSIONS: SymNose is a practical and reliable tool for the retrospective assessment of large caseloads of 2D photographs of cleft patients for research purposes. Moderate to high single inter-observer reliability was found. For future research with SymNose reliable outcomes can be achieved by using the average outcomes of single tracings of two observers. PMID- 27562105 TI - Telomere Length: The Intersection of Sociology, Molecular Biology, and Human Disease. PMID- 27562107 TI - All-Cause Mortality for Diabetics or Individuals with Hyperglycemia Applying for Life Insurance. AB - Diabetics and individuals with lab results consistent with a diagnosis of diabetes or hyperglycemia were extracted from data covering US residents who applied for life insurance between January 2007 and January 2014. Information about these applicants was matched to the Social Security Death Master File (SSDMF) and another commercially available death source file to determine vital status. Due to the inconsistencies of reporting within the death files, there were two cohorts of death cases, one including the imputed year of birth (full cohort of deaths), and the second where the date of birth was known (reduced cohort of deaths). The study had approximately 8.5 million person-years of exposure. Actual to expected (A/E) mortality ratios were calculated using the Society of Actuaries 2008 Valuation Basic Table (2008VBT) select table, age last birthday and the 2010 US population as expected mortality rates. With the 2008VBT as an expected basis, the overall A/E mortality ratio was 3.15 for the full cohort of deaths and 2.56 for the reduced cohort of deaths. Using the US population as the expected basis, the overall A/E mortality ratio was 0.98 for the full cohort of deaths and 0.79 for the reduced cohort. Since there was no smoking status information in this study, all expected bases were not smoker distinct. A/E mortality ratios varied by disease treatment category and were considerably higher in individuals using insulin. A/E mortality ratios decreased with increasing age and took on a J-shaped distribution with increasing BMI (Body Mass Index). The lowest mortality ratios were observed for overweight and obese individuals. The A/E mortality ratio based on the 2008VBT decreased with the increase in applicant duration, which was defined as the time since initial life insurance application. PMID- 27562108 TI - 2014 CRL Build Study of Life Insurance Applicants. AB - Objective .- Determine the impact of build on insurance applicant mortality accounting for smoking, laboratory test values and blood pressure. Method .- The study consisted of 2,051,370 applicants tested at Clinical Reference Laboratory between 1993 and 2007 with build and cotinine measurements available whose body mass index (BMI) was between 15 and 47. Vital status was determined as of September, 2011 by the Social Security Death Master File. Excluded from the primary study were applicants with HbA1c values >=6.5%, systolic BP >=141 mmHg, albumin values <=3.3 g/dL or total cholesterol values <=130 mg/dL. Relative mortality was determined by Cox regression analysis for bands of BMI split by age, sex and smoking status (urine cotinine positive). Results .- A majority of applicants had BMI >24 (overweight or obese by WHO criteria). After the exclusions noted above, relative mortality does not increase by >34% unless BMI is <20 (<18 for female non-smokers age 18 to 59) or BMI is >34. BMI values in the range of 22 to 24 and 25 to 29, overall, had similar and the lowest relative risks. For most nonsmokers, risk was lowest in the lower of these two BMI bands but for smokers (and non-smoking males age 60 to 89) risk was lowest in the higher BMI band. Additional analysis showed limited reduction in relative risk by accounting for all laboratory test values as well as continuing the exclusions. Eliminating the exclusions resulted in only a modest increase in relative risk because the mortality rate of the reference band increased as well. Conclusion .- After excluding elevated HbA1c and blood pressure (associated with high BMI) and low albumin and cholesterol (associated with low BMI) which are usually evaluated separately, mortality varies by a limited degree for BMI 20 to 34. Accounting for the mortality impact of other test values, in addition to the exclusions noted, reduced mortality associated with high BMI to a limited extent, but had little impact on mortality associated with low BMI. PMID- 27562109 TI - Regular Expressions: The Build Study Vignette. AB - The author creates a fictional vignette to illustrate how a medical director can use data analysis to help review cases comparing attending physician statement (APS) values for build vs those reported by the paramedical examiners for the same lives. In this first of two articles, a method for extracting suitable data is explored. PMID- 27562110 TI - Primary Sjogren's Syndrome White Matter Changes and Cognitive Dysfunction. AB - This case report describes a 52-year-old, female applicant for long term-care insurance with a history of an autoimmune connective tissue disease initially diagnosed as systemic lupus erythematosus (SLE). Over several years, the signs and symptoms evolved into a clear diagnosis of primary Sjogren's syndrome (PSS). The specific criteria for this diagnosis are reviewed including the symptoms, antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), abnormal salivary scintigraphy and positive Schirmer test. Symptoms of neuropathy and the possibility of a cognitive dysfunction are discussed as part of PSS. The association of white matter lesions (WML) with PSS is significant for underwriting consideration. PMID- 27562111 TI - Choroidal Nevi. AB - Choroidal nevi are common benign melanocytic lesions of the posterior uvea. PMID- 27562112 TI - Simulation of water impregnation through vertically aligned CNT forests using a molecular dynamics method. AB - The flow rate of water through carbon nanotube (CNT) membranes is considerably large. Hence, CNT membranes can be used in nanofluidic applications. In this work, we performed a molecular dynamics (MD) simulation of the introduction of water into CNTs in the CNT membranes, especially in vertically aligned CNT forests. The results showed that the Knudsen number (Kn) increased with an increasing volume fraction of CNT (VC) and was greater than 10(-3) for each VC. Beyond this value, the flow became a slip flow. Further, the permeability increased as VC increased in the actual state calculated by the MD simulation, whereas the permeability in the no-slip state predicted by the Hagen-Poiseuille relationship decreased. Thus, a clear divergence in the permeability trend existed between the states. Finally, the flow enhancement ranged from 0.1 to 23,800, and the results show that water easily permeates as VC increases. PMID- 27562113 TI - Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast. AB - BACKGROUND: T-lymphoma invasion and metastasis-inducing protein 1 (Tiam1) has been implicated in tumor occurrence and progression. Recent studies have shown that high expression levels of Tiam1 protein appear to be associated with the progression of numerous human tumors. This study attempted to explore the role of Tiam1 protein in tumor progression and the prognostic evaluation of breast cancer. METHODS: The localization of the Tiam1 protein was determined in the MDA MB-231 breast cancer cell line using immunofluorescence (IF) staining. In addition, a total of 283 breast tissue samples, including 153 breast cancer tissues, 67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues, were analyzed by immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics was evaluated by Chi-square test and Fisher's exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were performed by the Cox proportional hazards regression models. RESULTS: Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells; however, nuclear staining was also observed. Tiam1 protein expression was significantly higher in breast cancers (42.5 %, 65/153) and DCIS (40.3 %, 27/67) than in adjacent non-tumor tissues (12.7 %, 8/63). In addition, Tiam1 associated with tumor stage and Ki-67 expression, but negatively correlated with receptor tyrosine-protein kinase erbB-2 (Her2) expression. Moreover, survival analyses showed that DFS and 10-year OS rates were significantly lower in breast cancer patients with high Tiam1 expression than those with low Tiam1 expression. Univariate analysis suggested that molecular types, clinical stage, Her2 expression levels and Tiam1 expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients. Furthermore, multivariate analysis suggested that Tiam1 expression is a significant independent prognostic factor along with tumor stage in patients with breast cancer. CONCLUSIONS: Tiam1 expression is frequently up-regulated in breast cancer. Tiam1 expression correlated with clinicopathological parameters, suggesting that it may be a useful prognostic biomarker and potential therapeutic target for patients with breast cancer. PMID- 27562115 TI - Exercise barriers and the relationship to self-efficacy for exercise over 12 months of a lifestyle-change program for people with heart disease and/or diabetes. AB - BACKGROUND: Barriers to exercise are common in people with coronary heart disease (CHD) and/or diabetes mellitus (DM), and may influence self-efficacy for exercise. PURPOSE: The purpose of this study was to describe the exercise barriers experienced by people who have CHD and/or DM participating in the Healthy Eating and Exercise Lifestyle Program and to determine whether these barriers influence self-efficacy. METHODS: Participants ( n = 134) identified their barriers to exercise and completed the self-efficacy for exercise survey at baseline, at 4 months (following structured and supervised exercise) and at 12 months (following home-based exercise with three follow-up calls). RESULTS: The sample mean age was 63.6 years (SD 8.5) and 58% were male. Barriers to exercise were reported by 88% at baseline, 76% at 4 months, and 47% at 12 months. The most common barriers were lack of motivation (40.3%), lack of time overall (30.6%), and lack of time due to family commitments (17.2%). Only motivation changed significantly over time from baseline (40%) to 4 months (23%, p = 0.040). Lower self-efficacy for exercise was associated with lack of motivation at 12 months only, more depressive symptoms at baseline and 4 months, and a CHD diagnosis and higher body mass index at 12 months. In contrast, male gender and having higher self-efficacy at baseline were associated with higher self-efficacy for exercise at 4 and 12 months. CONCLUSION: Patients identified many exercise barriers despite participating in a lifestyle-change program. Lack of motivation negatively influenced self-efficacy for exercise at 12 months. Other factors needing attention include baseline self-efficacy, depressive symptoms, being female, being more overweight, and having CHD. PMID- 27562114 TI - Prognostic Value of Admission Blood Glucose in Diabetic and Non-diabetic Patients with Intracerebral Hemorrhage. AB - We aimed to validate prognostic value of elevated admission blood glucose (ABG) for clinical outcomes in diabetic and non-diabetic patients with intracerebral hemorrhage (ICH) in a representative large cohort. Data of ICH patients with onset time <=24 h were derived from the China National Stroke Registry. Clinical outcomes included 3-month poor outcome (death or dependency) and death. Logistic regression was performed for the association between ABG and clinical outcomes, both in the entire cohort and in patients with and without diabetes mellitus. 2951 ICH patients were enrolled, including 267 (9.0%) diabetics. In the entire cohort, there was a trend to increased risk of poor outcome with increasing ABG levels (adjusted OR 1.09; 95% CI, 1.04-1.15; P < 0.001). The risk of poor outcome was significantly greatest for the highest quartile (>=7.53 mmol/L) of ABG (adjusted OR 1.54; 95% CI, 1.17-2.03; p = 0.002, P for trend 0.004). We got similar association in non-diabetics but not in diabetics. Elevated ABG confers a higher risk of poor outcome in non-diabetics than diabetics with similar glucose level. Elevated ABG is an independent predictor of 3-month poor outcome in ICH patients, the prognostic value of which is greater in non-diabetics than diabetics with similar glucose level. PMID- 27562116 TI - The disunity of cultural group selection. AB - I argue that demographic selection, migration, and cultural diffusion, three mechanisms of institutional change, have little in common. Two of these lack the key features associated with group selection: they do not present us with group level selection pressures counteracting individual-level ones, need not produce behavioral altruism, and do not require competition between groups whose members cooperate preferentially with one another. Cultural norms vary, change, and influence cooperation; but that is not group selection. PMID- 27562118 TI - Label-Free Electric Monitoring of Human Cancer Cells as a Potential Diagnostic Tool. AB - Dielectrophoresis is widely used for cell characterization, and the exerted force on cells depends on the difference of polarizability between the latter and the surrounding medium. This physical phenomenon is translated by the real part of the Clausius-Mossotti factor. It is mostly modeled from the imaginary part, measured by electrorotation. The method described here measures experimentally the real part of the Clausius-Mossotti factor. It relies on the cell velocity when submitted to pure dielectrophoresis, and it was conducted on several human cell lines, at different times. A variety of cell lines was evaluated, from different organs or representative of different stages of cancer, with promising findings for early cancer detection. PMID- 27562119 TI - Reversible changes of canavalin solubility controlled by divalent cation concentration in crude sword bean extract. AB - Canavalin is a vicilin-class (7S) storage protein found in sword bean (Canavalia gladiata). Our previous report indicated that canavalin is precipitated by the addition of 20 mM MgCl2 to crude sword bean extract. Here, we examined the solubility changes induced by the addition of Mg2+ and Ca2+ at various concentrations. Canavalin tended to be insolubilized at relatively low concentrations of MgCl2 (< 20 mM) and solubilized at relatively high concentrations (> 20 mM). In addition, canavalin was slightly insolubilized in the presence of NaCl. Overall, the results revealed that solubility changes are reversible and depend on the concentration of divalent cations. Therefore, we suggested a reaction scheme that describes the effects of divalent cations on the solubility of canavalin, which would facilitate the study of its physiological function and the application of canavalin in the food processing industry. PMID- 27562117 TI - Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice. AB - BACKGROUND: Alphaviruses can cause fatal encephalitis in humans. Natural infections occur via the bite of infected mosquitos, but aerosol transmissibility makes some of these viruses potential bioterrorism agents. Central nervous system (CNS) host responses contribute to alphavirus pathogenesis in experimental models and are logical therapeutic targets. We investigated whether reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity within the CNS contributes to fatal alphavirus encephalitis in mice. METHODS: Infected animals were treated systemically with the angiotensin receptor-blocking drug, telmisartan, given its ability to cross the blood-brain barrier, selectively block type-1 angiotensin receptors (AT1R), and inhibit Nox-derived ROS production in vascular smooth muscle and other extraneural tissues. Clinical, virological, biochemical, and histopathological outcomes were followed over time. RESULTS: The importance of the angiotensin II (Ang II)/AT1R axis in disease pathogenesis was confirmed by demonstrating increased Ang II levels in the CNS following infection, enhanced disease survival when CNS Ang II production was suppressed, increased AT1R expression on microglia and tissue-infiltrating myeloid cells, and enhanced disease survival in AT1R deficient mice compared to wild-type (WT) controls. Systemic administration of telmisartan protected WT mice from lethal encephalitis caused by two different alphaviruses in a dose-dependent manner without altering virus replication or exerting any anti-inflammatory effects in the CNS. Infection triggered up regulation of multiple Nox subunits in the CNS, while drug treatment inhibited local Nox activity, ROS production, and oxidative neuronal damage. Telmisartan proved ineffective in Nox-deficient mice, demonstrating that this enzyme is its main target in this experimental setting. CONCLUSIONS: Nox-derived ROS, likely arising from CNS myeloid cells triggered by AT1R signaling, are pathogenic during fatal alphavirus encephalitis in mice. Systemically administered telmisartan at non-hypotensive doses targets Nox activity in the CNS to exert a neuroprotective effect. Disruption of this pathway may have broader implications for the treatment of related infections as well as for other CNS diseases driven by oxidative injury. PMID- 27562120 TI - Sphingoaurantiacus capsulatus sp. nov., isolated from mountain soil, and emended description of the genus Sphingoaurantiacus. AB - A novel Gram-stain-negative, strictly aerobic, non-motile, rod-shaped, capsule forming bacterium, designated strain YLT33T, that formed orange-red colonies was isolated from mountain cliff soil from Enshi Grand Canyon, southwest China. Growth occurred at 4-35 degrees C (optimum 28 degrees C) and at pH 6.0-10.0 (optimum 7.0). It showed maximum (99.3 %) 16S rRNA gene sequence similarity and formed a monophyletic clade with Sphingoaurantiacus polygranulatusMC 3718T (=CCTCC 2014274T). The DNA G+C content was 68.5 mol% and strain YLT33T showed a 50.5 % DNA-DNA relatedness value to S. polygranulatusMC 3718T. The major fatty acids (>5 %) were C17 : 1omega6c (40.7 %), C15 : 0 (10.4 %), C15 : 1omega6c (9.4 %), summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH; 8.6 %), C17 : 1omega8c (7.1 %), C18 : 1omega7c (6.1 %), and C15 : 0 2-OH (5.7 %). Ubiquinone-10 was the sole respiratory quinone. The polar lipids of strain YLT33T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid, two unknown glycolipids and one unknown phospholipid. Carotenoids were present in cells. Homospermidine was the major polyamine. In addition, strain YLT33T showed obvious differences from the closely related strain S. polygranulatusMC 3718T with respect to major polar lipids, fatty acids and other morphological, physiological and biochemical characteristics. These results from polyphasic taxonomic studies reveal that strain YLT33T represents a novel species of the genus Sphingoaurantiacus, for which the name Sphingoaurantiacuscapsulatus sp. nov. is proposed. The type strain is YLT33T (=CCTCC AB 2015150T=KCTC 42644T). PMID- 27562121 TI - Detection of selection signatures of population-specific genomic regions selected during domestication process in Jinhua pigs. AB - Chinese pigs have been undergoing both natural and artificial selection for thousands of years. Jinhua pigs are of great importance, as they can be a valuable model for exploring the genetic mechanisms linked to meat quality and other traits such as disease resistance, reproduction and production. The purpose of this study was to identify distinctive footprints of selection between Jinhua pigs and other breeds utilizing genome-wide SNP data. Genotyping by genome reducing and sequencing was implemented in order to perform cross-population extended haplotype homozygosity to reveal strong signatures of selection for those economically important traits. This work was performed at a 2% genome level, which comprised 152 006 SNPs genotyped in a total of 517 individuals. Population-specific footprints of selective sweeps were searched for in the genome of Jinhua pigs using six native breeds and three European breeds as reference groups. Several candidate genes associated with meat quality, health and reproduction, such as GH1, CRHR2, TRAF4 and CCK, were found to be overlapping with the significantly positive outliers. Additionally, the results revealed that some genomic regions associated with meat quality, immune response and reproduction in Jinhua pigs have evolved directionally under domestication and subsequent selections. The identified genes and biological pathways in Jinhua pigs showed different selection patterns in comparison with the Chinese and European breeds. PMID- 27562123 TI - Malthus redux, and still blind in the same eye. AB - Gowdy & Krall (G&K) essentially recapitulate Malthus's classic argument for ecological pessimism in modern biological dress. Their reasoning also reproduces Malthus's blindness to the implications of technological innovation. Agriculture might have suppressed human individualism as G&K insist, but technology has tended to foster it. This complicates human ecological prospects in a non Malthusian way, and it might additionally provide the resources for deliverance from disaster. PMID- 27562122 TI - The impact of intravenous thrombolysis on outcome of patients with acute ischemic stroke after 90 years old. AB - BACKGROUND: Age increases the risk of mortality and poor prognosis following stroke. The benefit of intravenous thrombolysis in very old patients remains uncertain. The purpose of the study was to evaluate the efficacy and safety of thrombolysis in very old patients considering their perfusion-imaging profile. METHODS: We conducted a retrospective study including patients older than 90 y.o. admitted for an acute ischemic stroke. A computed tomography perfusion-imaging (CTP) was performed in patients who received thrombolysis. Primary outcome was the functional status at 3 months, assessed by the modified Rankin scale (mRS). Secondary outcomes were the rate of hemorrhagic transformations, duration of hospitalization and the rate of death in the first 7 days. Patients receiving thrombolysis were compared with an age-matched group of non-thrombolysed patients. RESULTS: 78 patients were included (31 % male, aged 92 +/- 1.7 y.o). 37 patients received thrombolysis and among them, 30 had CTP with a mismatch. The three months mRS was not significantly different in the two groups (mRS 0-2: 5 % and 7 % in the thrombolysed and non-thrombolysed group, respectively). Hemorrhagic transformations were more frequent in the thrombolysed group (54 % versus 12 %, p = 0.002) and symptomatic intracranial hemorrhage tended to be associated with mRS at three months and death in the first 7 days. Duration of hospitalization was longer in the thrombolysed group (10 days +/- 12 versus 7 days +/- 9, p = 0.046). CONCLUSIONS: Patients who received thrombolysis did not have a better functional prognosis than non-thrombolysed patients. PMID- 27562124 TI - Reason for optimism: How a shifting focus on neural population codes is moving cognitive neuroscience beyond phrenology. AB - Multivariate pattern analysis can address many of the challenges for cognitive neuroscience highlighted in After Phrenology (Anderson 2014) by illuminating the information content of brain regions and by providing insight into whether functional overlap reflects the recruitment of common or distinct computational mechanisms. Further, failing to consider submaximal but reliable population responses can lead to an overly modular account of brain function. PMID- 27562125 TI - Rutin, an antioxidant flavonoid, induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium-induced oxidative stress in the testis of adult rats. AB - Exposure to cadmium (Cd) reduces sperm quality and induces oxidative stress in the testis. Rutin is an effective antioxidant flavonoid. We studied the effect of ethanol (EtOH, 5 g/kg b.wt.) intake on Cd (50 mg/kg b.wt.)-induced testicular toxicity with or without RUT pre-treatment (25, 50, 100 mg/kg b.wt.) in rats. At the end of the 15-day oral treatment, co-treatment with EtOH decreased the activities of glutathione (GSH), GSH-peroxidase and superoxide dismutase resulting to slight increase in the testicular MDA level compared to Cd-treated rats. The Cd+EtOH animals had higher levels of abnormal spermatozoa, decreased epididymal sperm number and serum testosterone levels (p < .05) compared to the Cd-treated animals. Rutin co-administration protected against the EtOH effects in a dose-dependent manner, with the Cd+EtOH+50 mg/kg RUT- and Cd+EtOH+100 mg/kg RUT treated animals having higher GSH and GSH-Px activities beyond the control values (p < .05). In a supplementary study, animals treated daily with RUT alone (25, 50, 100 mg/kg b.wt.) for 15 days dose-dependently increased testicular GSH peroxidase and GSH activities by 9.38%, 31.25%, 56.25% and 7.14%, 32.14%, 60.71%, respectively, compared to control values. Therefore, RUT induces GSH and GSH-Px activities to protect against Cd+EtOH-induced testis oxidative stress in rats. PMID- 27562126 TI - Oxidative stress equilibrium during obstetric event in normal pregnancy. AB - OBJECTIVE: The aim of this study was to determine malondialdehyde (MDA) concentration as an oxidative stress marker and total antioxidant capacity (TAC) in pregnancy before and after perinatal event. METHODS: This study was performed on 200 healthy full-term pregnant women admitted to pregnancy resolution in Maternal-Child Hospital of Durango, Mexico. Oxidative stress and TAC were assessed through detection of lipid peroxidation by quantitation of thiobarbituric acid-reactive substances (TBARS) and TAC through ferric reducing ability of the plasma (FRAP). RESULTS: Our results showed increased levels of MDA after vaginal delivery (VD). TAC was also increased after obstetric event, but it did not differ between VD and caesarean section. CONCLUSIONS: We demonstrated that MDA concentrations are increased two hours after obstetric event, and this increase correlates with VD. The TAC was increased as a compensatory mechanism during obstetric event. Another important finding is that women receiving analgesia administration in VD, as well as dexamethasone administration in caesarean section, experienced a protector effect that decreased MDA levels. PMID- 27562127 TI - [Approach to joint effusion]. AB - The fundamental components of the differential diagnostics of joint effusions are the patient history and clinical examination. In the case of unclear findings, arthrosonography can provide information for the distinction between intra articular and extra-articular pathologies. In atraumatic joint effusions inflammatory parameters in blood are determined in order to differentiate between systemic inflammatory and local inflammatory joint effusions. In the case of normal values further diagnostics are carried out using imaging. With elevated inflammatory parameters the main differential diagnoses are gouty arthritis, autoimmune joint processes and septic arthritis. When in doubt, a joint aspiration and synovial fluid analysis should be performed to rule out septic arthritis or if necessary confirmation of gouty arthritis. PMID- 27562128 TI - [Bizarre parosteal osteochondromatous proliferation of the metatarsal bone]. AB - A bizarre parosteal osteochondromatous proliferation (BPOP), also known as a Nora lesion, is a rare benign bone formation. It emanates mainly from the intact cortex of the metaphysis of short tubular bones (hands or feet). Conventional radiographs should be complemented using cross-sectional imaging modalities (CT/MRI). In the absence of symptoms a non-operative regime with radiological and clinical controls is possible. If symptomatic, excision biopsy is the treatment of choice, though a high recurrence rate has been reported. Histopathological examination confirms the diagnosis and typically shows an endochondral ossification zone and an unusually mineralized cartilaginous matrix referred to as "blue bone". PMID- 27562129 TI - Right Heart Function of Fetuses and Infants with Large Ventricular Septal Defect: A Longitudinal Case-Control Study. AB - The objective of this study was to detect the effect of a large ventricular septal defect (VSD) on right ventricular function before and after birth. All consecutive children with large VSD who were born in our hospital between January 2013-February 2016 and followed up throughout early infancy, and who lacked malformations or chromosomal abnormalities, were identified by a retrospective review of the medical records and included in this retrospective longitudinal case-control study (n = 30). Thirty normal control cases with an equivalent gestational age and gender served as controls. Tricuspid annular plane systolic excursion (TAPSE), right ventricle (RV) Tei index, and tricuspid E/E m were measured in the fetal, neonatal (day 1-28), and infant (day 29-70) periods. In all periods, the VSD and control groups did not differ in TAPSE values, but VSD associated with higher Tei indices and tricuspid E/E m values (in the fetal period: VSD group RV Tei was 0.48 +/- 0.12 and E/E m was 11.84 +/- 1.53, control group RV Tei was 0.42 +/- 0.16 and E/E m was 10.16 +/- 1.61; in neonatal period: VSD group RV Tei was 0.41 +/- 0.17 and E/E m was 12.21 +/- 1.59, control group RV Tei was 0.30 +/- 0.13 and E/E m was 7.20 +/- 1.28; in the infant period: VSD group RV Tei was 0.39 +/- 0.09 and E/E m was 11.89 +/- 2.80, control group RV Tei was 0.28 +/- 0.12 and E/E m was 5.26 +/- 1.90, all p < 0.05). In the fetal and neonatal periods, TAPSE correlated negatively with Tei index and tricuspid E/E m in both groups. However, in the infant period, only the control group exhibited correlations between TAPSE and Tei index or tricuspid E/E m. Tei index correlated positively with tricuspid E/E m in both groups in all three periods. The VSD group had smaller correlation coefficients than the control group. Large VSD may already start to impair RV diastolic and global function before birth. This impairment continued and increased after birth. These changes did not associate with obvious RV longitudinal systolic function impairment. Large VSD mainly affected RV function by decreasing diastolic function and myocardial performance. PMID- 27562130 TI - Evaluation of Impedance Cardiography for Measurement of Stroke Volume in Congenital Heart Disease. AB - Noninvasive measurement of cardiac output (CO) and particularly stroke volume (SV) remain difficult but potentially valuable. These variables can be particularly challenging to measure in children with congenital heart disease (CHD). Impedance cardiography (IC) is a technique shown to be accurate in measuring SV in adults and in children with structurally normal hearts. The ease of use and rapidity of SV measurement using IC makes it potentially attractive for young patients with CHD. Advances in IC technology have led to more sophisticated signal-morphology IC (SMIC) devices that may further improve accuracy. We tested the accuracy of SMIC to measure SV in 21 subjects with CHD by comparing measurements with those from cardiac magnetic resonance (CMR) imaging. There was good agreement between SMIC and CMR in measurement of SV: mean difference = 1.7 ml (p = 0.47); r = 0.89. The agreement and correlation persisted when controlling for the differences in blood pressure and heart rate during the two testing methods. We conclude that SMIC is accurate at measuring SV and thus CO when compared to CMR in a variety of forms of CHD. PMID- 27562131 TI - Radiofrequency Ablation in the Sinus of Valsalva for Ventricular Arrhythmia in Pediatric Patients. AB - The need to perform catheter ablation of ventricular arrhythmia from within the sinuses of Valsalva in a pediatric patient is uncommon. This has been reported in adults, but there are little data about the feasibility, safety or efficacy of catheter ablation in the sinuses of Valsalva in the pediatric patients. This is a retrospective review of all patients aged 18 years or less, at two separate institutions with no structural heart disease that underwent an ablation procedure for ventricular arrhythmia mapped to the sinus of Valsalva from 2010 to 2015. We identified 8 total patients meeting inclusion criteria. Median age was 16 years and the median weight was 61 kg. All patients were symptomatic or had developed arrhythmia-induced ventricular dysfunction. Ablation was performed in the left sinus in 4 patients and the right sinus in 4 patients. No ablations were required in the non-coronary sinus. All 8 patients had an acutely successful ablation using radiofrequency energy. There were no complications. At a mean follow-up of 7 months (4-15 months), all patients were known to be living. Follow up data regarding arrhythmia were available in 6 of the 8 patients, and none had recurrence of their ventricular arrhythmia off of all antiarrhythmic medications. Radiofrequency catheter ablation of ventricular arrhythmia in the sinus of Valsalva can be done safely and effectively in pediatric patients. PMID- 27562132 TI - Effectiveness of Radiofrequency Catheter Ablation of Outflow Tract Ventricular Arrhythmias in Children and Adolescents. AB - Outflow tract ventricular arrhythmias (OTVAs) are common in children; however, experience is limited on their radiofrequency catheter ablation (RFCA). The purpose of this study was to assess the outcomes of mapping and ablation of pediatric OTVAs and to evaluate the role of ECG algorithms in distinguishing the origin of OTVAs. We compared retrospectively collected single-center data on 92 consecutive pediatric patients (58 male; age, 8.2 +/- 2.9 [range 3.6-18] years) who underwent RFCA for OTVAs from 2009 to 2015. Two independent and blinded observers analyzed ECG data. Of these children, 69 (75 %) were of RVOT origin. RFCA was given up in 1 case, and the acute success rate was 92.3 % (84/91), the 1 year follow-up recurrence rate was 8.3 % (7/84) and the complications of the procedure were 2.2 % (2/92). And 3D versus 2D mapping-guided RFCA was associated with significantly (p < 0.05) higher acute success rate (96.1 % [49/51] vs. 87.5 % [35/40]), and lower X-ray exposure (742.5 +/- 323.1 vs. 1432.3 +/- 605.5 mGy cm2) and 1-year recurrence rate (4.1 % [2/49] vs. 14.3 % [5/35]). The positive predictive value of four types of ECG algorithms used in adults for LVOT origin was only 47.7-65.4 %. In these cases, four identified as RVOT origin and two identified as LVOT origin by ECG underwent successful ablation on the other side of outflow tract finally. And these six children who underwent successful RFCA in both sides of outflow tract had no follow-up recurrence. OTVAs in children originate mostly from RVOT. RFCA can be used for ablation of pediatric OTVAs effectively and safely. In some cases, successful RFCA should be ablated in both sides of outflow tract. ECG-based prediction of OTVA origin as used in adults is limited in children. PMID- 27562133 TI - Differences by Altitude in the Frequency of Congenital Heart Defects in Colombia. AB - More evidence is needed that links the diagnosis of different congenital heart diseases (CHD) identified after birth, with intermediate altitudes above sea level in geographically and ethnically diverse populations. Our aim was to estimate relative frequencies of CHD diagnosis by altitude and gender in the pediatric population of 12 cities in Colombia. This was a cross-sectional study based on the information collected between 2008 and 2013 in Colombia, during annual congenital heart disease (CHD) case detection campaigns in the post-natal period. All children underwent physical examination, pulse-oximetry, and echocardiography. The odds ratio (OR) was used as the summary statistic to assess associations with altitude in the relative frequency of CHD diagnosis. Data from 5900 children who attended the campaigns were evaluated (54.3 % male), out of which 3309 (56.1 %) were diagnosed with CHD. There were statistically significant differences in the relative distribution of the different CHD by city altitude and gender (p < 0.0001). When compared with sea level, altitudes between 1285 and 3000 m above sea level were associated with increased Patent Ductus Arteriosus (PDA) (ORmh 1.68, 95 % CI 1.34-2.09; p < 0.0001) and left ventricular outflow tract obstruction (LVOTO) diagnoses (ORmh 2.06, 95 % CI 1.63-2.61; p < 0.0001), while the opposite was true for right ventricular outflow tract (RVOTO) diagnosis (OR 0.60; 95 % CI 0.49-0.74, p < 0.0001). These associations were not modified by gender differences. In a geographically and ethnically diverse population, altitudes between 1285 and 3000 m above sea level carried an independent and clinically important excess diagnostic risk of PDA and of LVOTO, when compared to all other CHD. PMID- 27562134 TI - A Flexible Quasi-Solid-State Nickel-Zinc Battery with High Energy and Power Densities Based on 3D Electrode Design. AB - A flexible quasi-solid-state Ni-Zn battery is developed by using tiny ZnO nanoparticles and porous ultrathin NiO nanoflakes conformally deposited on hierar chical carbon-cloth-carbon-fiber (CC-CF) as the anode (CC-CF@ZnO) and cathode (CC CF@NiO), respectively. The device is able to deliver high performance (absence of Zn dendrite), superior to previous reports on aqueous Ni-Zn batteries and other flexible electrochemical energy-storage devices. PMID- 27562136 TI - Traceless OH-Directed Wacker Oxidation-Elimination, an Alternative to Wittig Olefination/Aldol Condensation: One-Pot Synthesis of alpha,beta-Unsaturated and Nonconjugated Ketones from Homoallyl Alcohols. AB - A new method for one-pot synthesis of beta-substituted and beta,beta disubstituted alpha,beta-unsaturated methyl ketones from homoallyl alcohols by sequential PdCl2/CrO3-promoted Wacker process followed by an acid-mediated dehydration reaction has been developed. Remarkably, internal homoallyl alcohols delivered regioselectively nonconjugated unsaturated carbonyl compounds under the same protocol. A new starting material-based synthesis of alpha,beta-unsaturated and nonconjugated methyl ketones is demonstrated. PMID- 27562135 TI - Automated Enrichment, Transduction, and Expansion of Clinical-Scale CD62L+ T Cells for Manufacturing of Gene Therapy Medicinal Products. AB - Multiple clinical studies have demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved patient survival. The continuously increasing interest in those advanced gene therapy medicinal products (GTMPs) leads to a manufacturing challenge regarding automation, process robustness, and cell storage. Therefore, this study addresses the proof of principle in clinical-scale selection, stimulation, transduction, and expansion of T cells using the automated closed CliniMACS(r) Prodigy system. Naive and central memory T cells from apheresis products were first immunomagnetically enriched using anti-CD62L magnetic beads and further processed freshly (n = 3) or split for cryopreservation and processed after thawing (n = 1). Starting with 0.5 * 108 purified CD3+ T cells, three mock runs and one run including transduction with green fluorescent protein (GFP) containing vector resulted in a median final cell product of 16 * 108 T cells (32 fold expansion) up to harvesting after 2 weeks. Expression of CD62L was downregulated on T cells after thawing, which led to the decision to purify CD62L+CD3+ T cells freshly with cryopreservation thereafter. Most important in the split product, a very similar expansion curve was reached comparing the overall freshly CD62L selected cells with those after thawing, which could be demonstrated in the T cell subpopulations as well by showing a nearly identical conversion of the CD4/CD8 ratio. In the GFP run, the transduction efficacy was 83%. In-process control also demonstrated sufficient glucose levels during automated feeding and medium removal. The robustness of the process and the constant quality of the final product in a closed and automated system give rise to improve harmonized manufacturing protocols for engineered T cells in future gene therapy studies. PMID- 27562137 TI - The metronomic therapy with prednisone, etoposide, and cyclophosphamide reduces the serum levels of VEGF and circulating endothelial cells and improves response rates and progression-free survival in patients with relapsed or refractory non Hodgkin's lymphoma. AB - PURPOSE: There is an urgent need for a better strategy in the management of relapsed or refractory non-Hodgkin's lymphoma (NHL). The present study was designed to evaluate the efficacy and safety of the regimen using metronomic prednisone, etoposide, and cyclophosphamide in the treatment of patients with relapsed or refractory NHL, in comparison with conventional salvage chemotherapy. METHODS: Eligible patients were randomized to the test group (n = 23) receiving metronomic prednisone, etoposide, and cyclophosphamide or the control group (n = 21) receiving conventional salvage chemotherapy. The serum levels of circulating endothelial cells (CECs) and vascular endothelial growth factor (VEGF) were measured before and after two cycles of treatment; overall response rate (ORR) and disease control rate (DCR) were evaluated at cycles 2, 4, 6, and 12 months after treatment. RESULTS: After two cycles of treatment, the ORRs of the test and control groups were statistically similar, while the DCR of the test group (87.0 %) was significantly higher than that of the control group (57.1 %). At 12 months after treatment, the ORR and DCR of the test group (47.8 and 69.6 %, respectively) were significantly higher than that of the control group (19.0 and 33.3 %, respectively). The serum CECs and VEGF levels in the test group after treatment were significantly lower than that before treatment or that of the control group. In the patients with ORR and DCR in the test group, the serum CECs and VEGF levels remained relatively low at cycles 2, 4, and 6 and at 12 months after treatment. There was a progression-free survival (PFS) benefit of 6.5 months in the test group, compared with the control group. CONCLUSION: Metronomic chemotherapy with prednisone, etoposide, and cyclophosphamide resulted in higher ORR and DCR, fewer adverse effects, and longer PFS in patients with relapsed or refractory NHL, with significant reduction in serum CECs and VEGF levels. PMID- 27562138 TI - Automated optogenetic feedback control for precise and robust regulation of gene expression and cell growth. AB - Dynamic control of gene expression can have far-reaching implications for biotechnological applications and biological discovery. Thanks to the advantages of light, optogenetics has emerged as an ideal technology for this task. Current state-of-the-art methods for optical expression control fail to combine precision with repeatability and cannot withstand changing operating culture conditions. Here, we present a novel fully automatic experimental platform for the robust and precise long-term optogenetic regulation of protein production in liquid Escherichia coli cultures. Using a computer-controlled light-responsive two component system, we accurately track prescribed dynamic green fluorescent protein expression profiles through the application of feedback control, and show that the system adapts to global perturbations such as nutrient and temperature changes. We demonstrate the efficacy and potential utility of our approach by placing a key metabolic enzyme under optogenetic control, thus enabling dynamic regulation of the culture growth rate with potential applications in bacterial physiology studies and biotechnology. PMID- 27562141 TI - Factors Influencing Health-Related Quality of Life of Living-Donor Kidney Transplant Recipients: A Population-Based Study. AB - OBJECTIVES: Our objective was to explore factors influencing health-related quality of life in living-donor kidney transplant recipients. MATERIALS AND METHODS: A total of 140 kidney transplant recipients, enrolled between December 2014 and April 2015, were administered questionnaires on medical outcomes, 36 item Short Form Health Survey, medical coping modes, cognitive appraisal of health scale, and adverse effects of medications. Path analysis was employed to verify the hypothesized model. RESULTS: Increased serum creatinine level and high economic burden had direct positive effects on negative appraisal (beta = 0.18, P < .05 and beta = 0.46, P < .01). Adverse effects of medication had direct positive effects on confrontation; whereas negative appraisal had direct positive effect on acceptance-resignation (beta = 0.21, P < .05) and direct negative effect on physical component summary (beta = -0.43, P < .001) and mental component summary (beta = -0.51, P < .001). In addition, confrontation directly affected mental component summary (beta = -0.15, P < .05). The enrolled variables accounted for 25.0% of physical component summary variance and 35.4% of mental component summary variance. CONCLUSIONS: In this study, economic burden, serum creatinine levels, and adverse effects of immunosuppressive therapy were the key external factors, whereas patients' cognitive appraisal and coping strategies were the main internal factors affecting patients' health-related quality of life. Medical care providers attending to transplant recipients should be able to identify patients developing negative coping strategies in response to stressors and plan individualized counseling programs for these patients. PMID- 27562139 TI - A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice. AB - Connective tissue growth factor (CTGF) has been recognized as a central mediator and promising therapeutic target in hepatic fibrosis. In this study, we generated a novel virus-like particle (VLP) CTGF vaccine by inserting the 138-159 amino acid (aa) fragment of CTGF into the central c/e1 epitope of C-terminus truncated hepatitis B virus core antigen (HBc, aa 1-149) using a prokaryotic expression system. Immunization of BALB/c mice with the VLP vaccine efficiently elicited the production of anti-CTGF neutralizing antibodies. Vaccination with this CTGF vaccine significantly protected BALB/c mice from carbon tetrachloride (CCl4) induced hepatic fibrosis, as indicated by decreased hepatic hydroxyproline content and lower fibrotic score. CCl4 intoxication-induced hepatic stellate cell activation was inhibited by the vaccination, as indicated by decreased alpha smooth muscle actin expression and Smad2 phosphorylation. Vaccination against CTGF also attenuated the over-expression of some profibrogenic factors, such as CTGF, transforming growth factor-beta1, platelet-derived growth factor-B and tissue inhibitor of metalloproteinase-1 in the fibrotic mouse livers, decreased hepatocyte apoptosis and accelerated hepatocyte proliferation in the fibrotic mouse livers. Our results clearly indicate that vaccination against CTGF inhibits fibrogenesis, alleviates hepatocyte apoptosis and facilitate hepatic regeneration. We suggest that the vaccine should be developed into an effective therapeutic measure for hepatic fibrosis. PMID- 27562140 TI - Repeat procedures after second-generation cryoballoon ablation as an index procedure for persistent atrial fibrillation: one-year follow-up. AB - PURPOSE: Data indicate that the second-generation cryoballoon (Arctic Front Advance, Medtronic, Minnesota, USA) could be effective for persistent atrial fibrillation. However, electrophysiological findings and the midterm clinical outcome of repeat procedures following second-generation cryoballoon ablation are lacking. METHODS: Consecutive patients with drug-resistant persistent atrial fibrillation who underwent a repeat ablation due to arrhythmia recurrence following an index procedure with second-generation cryoballoon were retrospectively included in our analysis. A total of 24 patients were included. Twenty underwent repeat procedures because of atrial fibrillation or left atrial arrhythmias and four because of typical atrial flutter. Mean time to recurrence of atrial tachyarrhythmias was 6.6 +/- 3 months. Mean redo procedural time was 122 +/- 23 min. RESULTS: At a mean follow-up of 11.8 +/- 6.5 months, 15 patients (75 %) did not experience recurrence of atrial arrhythmias. Of the five patients (25 %) who had recurrence of atrial tachyarrhythmia, four presented with persistent atrial fibrillation and one with a mitral isthmus-dependent flutter. Of note is that the four patients with typical flutter were free from atrial tachycardia recurrence after the redo procedure. Two patients (9 %) underwent a third procedure. Mean time to recurrence of atrial arrhythmias from the repeat procedure was 9 +/- 1 months. CONCLUSIONS: Our findings show that repeat ablation procedures following a second-generation cryoballoon ablation for persistent atrial fibrillation result in 75 % of freedom from any atrial tachycardia at 12 months follow-up. Of the recurrences, 63 % were due to new onset of atrial fibrillation and 37 % to organized tachycardias. PMID- 27562143 TI - Mechanically Stable Intraspinal Microstimulation Implants for Human Translation. AB - The goal of this study was to develop stable intraspinal microstimulation (ISMS) implants for use in humans to restore standing and walking after spinal cord injury. ISMS electrically activates locomotor networks within the lumbar region of the spinal cord. In animals, ISMS produced better functional outcomes than those obtained by other interventions, and recent efforts have focused on translating this approach to humans. This study used domestic pigs to: (1) quantify the movements and length changes of the implant region of the spinal cord during spine flexion and extension movements; and (2) measure the forces leading to the dislodgement of the ISMS electrodes. The displacement of the spinal cord implant region was 5.66 +/- 0.57 mm relative to the implant fixation point on the spine. The overall length change of the spinal cord implant region was 5.64 +/- 0.59 mm. The electrode dislodgment forces were 60.9 +/- 35.5 mN. Based on these results, six different coil types were fabricated and their strain relief capacity assessed. When interposed between the electrodes and the stimulator, five coil types successfully prevented the dislodgement of the electrodes. The results of this study will guide the design of mechanically stable ISMS implants for ultimate human use. PMID- 27562142 TI - Thromboxane A2 exacerbates acute lung injury via promoting edema formation. AB - Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca(2+) channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca(2+)- and Rho kinase-dependent signaling. PMID- 27562144 TI - Postural Control of Elderly Adults on Inclined Surfaces. AB - This study analyzed the postural control of older adults on inclined surfaces, and was conducted in 17 elderly adults and 18 young adults of both genders. Ground reaction forces and moments were collected using two AMTI force platforms, one of which was in a horizontal position (HOR), while the other was inclined 14 degrees in relation to the horizontal plane. Each participant executed three 70 s-trials of bipedal standing with their eyes open and eyes closed in three inclination conditions: the HOR, the inclined position at ankle dorsi-flexion (UP), and the inclined position at ankle plantar-flexion (DOWN). Spectral analysis, global (mean velocity-Velm, ellipse area-Area and F80), and structural stabilometric descriptors (sway density curve-SDC, detrended fluctuation analysis DFA, sample entropy-SEn) were employed to assess the center of pressure sway. Velm and F80 were greater for the elderly, whereas SDC, DFA, and SEn were smaller for this group. Global, SDC and DFA variables were sensitive to visual deprivation, however the relative difference from the EO to EC condition was higher in young than in elderly. The DOWN condition was more stable than the UP condition for both young and older adults. With regard to the UP condition, the challenge observed is essentially associated with the corresponding biomechanical constraints. In conclusion, the elderly showed significant differences compared to the young, but age per se may not necessarily result in compromised postural control. PMID- 27562145 TI - Walking a Tightrope: Balancing the Risk of Diagnostic Error in Inpatient Pediatrics. PMID- 27562146 TI - Gold Nanomaterials in Consumer Cosmetics Nanoproducts: Analyses, Characterization, and Dermal Safety Assessment. AB - Establishment of analytical methods of engineered nanomaterials in consumer products for their human and environmental risk assessment becomes urgent for both academic and industrial needs. Owing to the difficulties and challenges around nanomaterials in complex media, proper chemical separation and biological assays of nanomaterials from nanoproducts needs to be firstly developed. Herein, a facile and rapid method to separate and analyze gold nanomaterials in cosmetics is reported. Gold nanomaterials are successfully separated from different facial or eye creams and their physiochemical properties are analyzed by quantitative and qualitative state-of-the art techniques with high sensitivity or high spatial resolution. In turn, a protocol including quantification of gold by inductively coupled plasma mass spectrometry and thorough characterization of morphology, size distribution, and surface property by electron microscopes, atomic force microscope, and X-ray photoelectron spectroscope is developed. Subsequently, the preliminary toxicity assessment indicates that gold nanomaterials in cosmetic creams have no observable toxicity to human keratinocytes even after 24 h exposure up to a concentration of 200 MUg mL-1 . The environmental scanning electron microscope reveals that gold nanomaterials are mostly attached on the cell membrane. Thus, the present study provides a full analysis protocol for toxicity assessment of gold nanomaterials in consumer products (cosmetic creams). PMID- 27562147 TI - Early signet ring cell carcinoma of the stomach is related to favorable prognosis and low incidence of lymph node metastasis. AB - BACKGROUND: The aim of this study was to evaluate the clinical characteristics of early signet ring cell carcinoma of the stomach (SRC) and to investigate the optimal treatment strategy for early SRC. METHODS: A total of 746 patients with pT1 gastric cancer (GC), who had undergone surgical resection between 1997 and 2012 were analyzed. Of these, 190 patients with SRC were enrolled in this study. RESULTS: (i) The patients with SRC showed a significantly longer overall survival (P = 0.012) and disease free survival (P = 0.004) than patients with the other histological types. Multivariate analysis identified SRC as an independent factor predicting favorable prognosis in pT1 GC (HR = 0.38; 95% CI: 0.11-0.96; P = 0.041). Specifically, in undifferentiated pT1 GC, SRC was significantly less associated with lymph node metastasis (LNM) (OR = 0.39; 95% CI: 0.15-0.96; P = 0.042). (ii) From the viewpoint of a histological mixed-type, pure-SRC with pT1a was not associated with LNM regardless of tumor size (0.0%, 0/110), whereas mixed SRC was an independent risk factor for LNM (OR = 7.19; 95% CI: 1.51-43.9; P = 0.012). CONCLUSIONS: Patients with early SRC have a favorable prognosis with a low incidence of LNM. However, care should be taken with mixed-SRC, which consists of SRC and other histological types. J. Surg. Oncol. 2016;114:607-612. (c) 2016 Wiley Periodicals, Inc. PMID- 27562148 TI - Lithium-ion battery electrolyte mobility at nano-confined graphene interfaces. AB - Interfaces are essential in electrochemical processes, providing a critical nanoscopic design feature for composite electrodes used in Li-ion batteries. Understanding the structure, wetting and mobility at nano-confined interfaces is important for improving the efficiency and lifetime of electrochemical devices. Here we use a Surface Forces Apparatus to quantify the initial wetting of nanometre-confined graphene, gold and mica surfaces by Li-ion battery electrolytes. Our results indicate preferential wetting of confined graphene in comparison with gold or mica surfaces because of specific interactions of the electrolyte with the graphene surface. In addition, wetting of a confined pore proceeds via a profoundly different mechanism compared with wetting of a macroscopic surface. We further reveal the existence of molecularly layered structures of the confined electrolyte. Nanoscopic confinement of less than 4-5 nm and the presence of water decrease the mobility of the electrolyte. These results suggest a lower limit for the pore diameter in nanostructured electrodes. PMID- 27562149 TI - Corrigendum: Oligodendrocyte, Astrocyte and Microglia Crosstalk in Myelin Development, Damage, and Repair. AB - [This corrects the article DOI: 10.3389/fcell.2016.00071.]. PMID- 27562150 TI - Nocturnal Blood Pressure Variability in Patients with Obstructive Sleep Apnea Syndrome. AB - Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. Blood pressure variability may be a sign of risk of cardiovascular events. The aim of this study was to investigate the hypothesis that severe OSA syndrome is associated with increased blood pressure variability. Based on respiratory polygraphy, 58 patients were categorized into two groups: severe OSA with apnea/hypopnea index (AHI) greater than 29 episodes per hour (mean 52.2 +/- 19.0/h) and mild-to-moderate OSA with AHI between 5 and 30 episodes per hour (mean 20.2 +/- 7.8/h). A 24-h noninvasive blood pressure monitoring was performed. The standard deviation of mean blood pressure was used as the indicator of blood pressure variability. In patients with severe, compared with mild-to-moderate OSA, a higher mean nocturnal systolic blood pressure (133.2 +/- 17.4 mmHg vs. 117.7 +/- 31.2 mmHg, p < 0.05) and diastolic blood pressure (80.9 +/- 13.1 mmHg vs. 73.8 +/- 9.2, p < 0.01), nocturnal systolic blood pressure variability (12.1 +/- 6.0 vs. 7.6 +/- 4.3, p < 0.01) and diastolic blood pressure variability (10.5 +/- 6.1 vs. 7.3 +/- 4.0 p < 0.05), nocturnal mean blood pressure variability (9.1 +/- 4.9 mmHg vs. 6.8 +/- 3.5 mmHg) were detected. The findings of the study point to increased nocturnal systolic and diastolic arterial blood pressure and blood pressure variability as risk factors of cardiovascular complications in patients with severe OSA. PMID- 27562151 TI - Scaling crossover in thin-film drag dynamics of fluid drops in the Hele-Shaw cell. AB - We study both experimentally and theoretically the descending motion due to gravity of a fluid drop surrounded by another immiscible fluid in a confined space between two parallel plates, i.e., in the Hele-Shaw cell. As a result, we show a new scaling regime of a nonlinear drag friction in viscous liquid that replaces the well-known Stokes' drag friction through a clear collapse of experimental data thanks to the scaling law. In the novel regime, the dissipation in the liquid thin film formed between the drop and cell walls governs the dynamics. The crossover of this scaling regime to another scaling regime in which the dissipation inside the droplet is dominant is clearly demonstrated and a phase diagram separating these scaling regimes is presented. PMID- 27562152 TI - [Surgical strategy for postburn facial scar contracture]. AB - Postburn facial scar contracture, which can cause disfigurement and functional impairment, is a major therapeutic challenge. Except for some scars with severe functional impairments such as ectropion of lid, obstruction of nostril, microstomia, and so on, other kinds of facial scars are recommended to be reconstructed after they become sufficiently softened. The selection of specific methods depends on the characteristics of the facial scar. The methods includ direct closure after resection, full or split-thickness skin transplantation, pedicled flap, distant flap, and free flap transfer, and tissue expansion. For the resurfacing of subtotal or total face deformity, composite facial tissue allotransplantation and prefabricated flap combined with tissue expansion and autologous fat injection are increasingly used to improve the facial aesthetic and functional outcome. PMID- 27562153 TI - [To improve the effect of reconstruction of scar contracture deformity on face and neck]. AB - This article briefly summarizes the methods for repair of scar contracture deformity on face and neck in recent years, including new technologies in this field. We can choose non-surgical treatment or surgical treatment to achieve the purpose of repair and reconstruction of scar contracture deformity on face and neck after considering the factors of function and appearance. PMID- 27562154 TI - [Reconstruction of postburn facial scar contracture deformity with expanded flap containing cervical cutaneous branch of transverse cervical artery]. AB - OBJECTIVE: To observe the effect of expanded flap containing cervical cutaneous branch of transverse cervical artery (TCA) on reconstruction of postburn facial scar contracture deformity. METHODS: Six patients with postburn facial scar contracture deformity, hospitalized from September 2011 to January 2016, with the scar area ranging from 12 cm*10 cm to 20 cm*15 cm, were reconstructed with expanded flap containing cervical cutaneous branch of TCA. One expander of 300 mL or 350 mL implanted in anterior pectoral area was injected for excessive expanding; one patient was conducted with expansion in both sides of the anterior pectoral area. The volume of expansion varied from 1 260 to 2 010 mL after 6 to 15 months. Two flaps were delayed for their poor blood supply. After expansion, the flaps with the area ranging from 20 cm*7 cm to 25 cm*9 cm were transferred with no tension to cover the wounds after scar excision. The donor site was closed directly. Three to four weeks later, the vascular pedicle was dissected combined with local reconstruct surgery. RESULTS: All the flaps survived, with two wounds suffered delayed healing. During the follow-up for 4 to 15 months, the flaps were thin and soft with good sensation and color close to the facial skin. CONCLUSIONS: Expanded flap containing cervical cutaneous branch of TCA is a good choice for reconstruction of postburn facial scar contracture deformity because of its good texture and color, thin thickness, as well as it can provide large avaliable area while causing less injury to the donor site. PMID- 27562155 TI - [Classification of massive postburn scars on neck and the reconstruction strategy using pre-expanded perforator flaps from the back]. AB - OBJECTIVE: To explore the classification of massive postburn scars on neck and the reconstruction strategy using pre-expanded perforator flaps from the back. METHODS: Thirty-seven patients with massive postburn scars on neck were admitted from January 2010 to December 2014 and treated by our treatment group. The massive postburn scars on neck were categorized into three types according to their size and location. Based on the principles of reconstructive ladder, matching in color and texture between donor site skin and neck skin, large size and thinner thickness of tissue of donor site skin, donor-recipient sites balance, and dominant supplying vessel, we proposed the following treatment strategy for choosing perforator flaps from the back. (1) In view of central cervical scar involving the central area (mainly in this area) and one side of peripheral zone, the free circumflex scapular artery perforator flap was chosen. (2) In view of peripheral cervical scar involving the central area and one side of peripheral zone (mainly in this area), the pedicled superficial cervical artery perforator flap was the first choice. In case the pedicled superficial cervical artery perforator flap was unavailable because of the absence of superficial cervical artery perforator or scarring within its vascular territory, the pedicled occipital artery perforator flap, pedicled dorsal scapular artery perforator flap, and free circumflex scapular artery perforator flap were chosen as alternative options considering specific condition. (3) In view of total cervical scar involving the central area and both sides of peripheral zone, the circumflex scapular artery perforator supercharged pedicled superficial cervical artery perforator flap was chosen. Tissue expansion was performed in the first stage for all the patients. In the second stage, after excision of the cervical scars, the flaps were transferred to cover the wounds. RESULTS: Among the 37 patients, 7 were with central cervical scar, 12 with total cervical scar, and 18 with peripheral cervical scar. Among patients with peripheral cervical scar, the pedicled superficial cervical artery perforator flaps were used in 11 cases, pedicled occipital artery perforator flaps in 2 cases, pedicled dorsal scapular artery perforator flap in 1 case, and free circumflex scapular artery perforator flaps in 4 cases. Tip necrosis occurred in 3 flaps of patients after surgery, which were healed by dressing change. The other flaps of patients grew well after surgery. Patients were followed up for 1 to 6 years, and all patients were able to extend neck beyond 110 degrees with no sense of restricted neck flexion or rotation. No contracture of flap was observed. Thirty-five patients were satisfied with their appearance after surgery. CONCLUSIONS: Pre-expanded perforator flaps from the back are useful flaps for reconstruction of massive postburn scar on neck. Free circumflex scapular artery perforator flap is recommended for reconstruction of central cervical scar. Pedicled superficial cervical artery perforator flap is the first option for reconstruction of peripheral cervical scar, while the pedicled occipital artery perforator flap, pedicled dorsal scapular artery perforator flap and free circumflex scapular artery perforator flap are alternative options. For total cervical scar, the circumflex scapular artery perforator supercharged pedicled superficial cervical artery perforator flap is recommended. PMID- 27562156 TI - [Aesthetic reconstruction strategy for postburn facial scar and its clinical effect]. AB - OBJECTIVE: To explore the aesthetic reconstruction strategy for postburn facial scar and its clinical effect. METHODS: Three hundred and forty-two patients with postburn facial scars were hospitalized from January 2000 to December 2015. Local expanded flap or deltopectoral expanded flap was used for reconstruction according to the location and size of the facial scar. The forehead expanded flap could be chosen for the scar in dorsum nasi or inferior eyelid. The local expanded flap was chosen when the scar width was smaller than 5 cm in cheek, chin, and marginal mandible region. The expanded deltopectoral flap was chosen when the scar width was larger than 5 cm in cheek, chin, and marginal mandible region or the scar contracture was too serious to cause displacement of lips, nose, or eyelid, and the wound width was larger than 5 cm after release. The facial scars of 82 patients, with size ranged from 6.0 cm*2.5 cm to 15.0 cm*10.0 cm, were reconstructed with expanded local flaps. The facial scars of 260 patients, with size ranged from 8.0 cm*7.0 cm to 38.0 cm*13.0 cm, were reconstructed with expanded deltopectoral flaps. After expansion of 2 to 6 months, the facial scars were excised and completely released first of all. The transfer way of local flap and size of deltopectoral flap with pedicle were designed according to the size and shape of the wound. Three weeks after transfer of deltopectoral flap, flap delay procedure was conducted. One week later, the pedicle was severed from the flap to reconstruct the remaining scar. Anti-scar medicine, laser therapy, and elasticized fabric were used postoperatively on the scars in both donor and recipient sites. RESULTS: During the postoperative follow up for 3 to 12 months, the flaps of 40 out of 82 cases reconstructed with expanded local flaps were in good color and texture. Before 2008, mild scar hyperplasia was observed in the incision of 19 patients; with application of laser after 2008, the number of patients with scar hyperplasia was decreased. During the postoperative follow-up for 3 to 12 months, the flaps of 90 out of 260 cases reconstructed with expanded deltopectoral flaps were in good color and texture. The expander was exposed from the incision in 15 patients, while it did not affect the later treatment. Nine unilateral flaps showed poor blood circulation at the distal end, and they were healed after dressing change. In the early phase, necrosis was observed in one flap after transfer, and it was healed after transplantation of free skin graft. Scar hyperplasia was observed in the chest donor site of one patient, and it was improved after laser therapy. CONCLUSIONS: Postburn facial scar could be reconstructed with local or deltopectoral flaps, following the principle of similarity. The expansion could increase the size of the flaps, reduce the thickness of the flaps, and lower the donor site damage. PMID- 27562157 TI - [Clinical effects of different modes of ultra pulse carbon dioxide fractional laser used in combination on the treatment of hypertrophic scar on face and neck]. AB - OBJECTIVE: To explore the clinical effects of ultra pulse mode of ultra pulse carbon dioxide fractional laser combined with Deep FX mode or Scaar FX mode on the treatment of patients with hypertrophic scars on face and neck. METHODS: One hundred and fifty-eight patients with hypertrophic scars on face and neck who met the inclusion criteria were admitted to Hunan Provincial People's Hospital from January 2012 to January 2015. Firstly, the scar areas were cleaned and given compound lidocaine cream for surface anesthesia. Then the scar areas were treated with ultra pulse mode of ultra pulse carbon dioxide fractional laser, with energy from 150 to 175 mJ, frequency of 40 Hz, hole to hole distance of 4 mm or 5 mm, and the treatment time of each hole of 2 s or 3 s. For mild scar, Deep FX mode was added for treatment with energy from 30 to 50 mJ, frequency of 300 Hz, and density of 5%; for moderate and severe scar, Scaar FX mode was additionally used for therapy, with energy from 80 to 150 mJ, frequency of 300 Hz, and density of 3%. The above-mentioned treatments were performed per three months, totally for 3 times, 10-15 min per treatment. After each treatment, wounds were moisturized and given sun protection. Before the first treatment and 6 months after treatment of 3 times, the curative effect was assessed by Vancouver Scar Scale (VSS) and University of North Carolina Scar Scale. Six months after treatment of 3 times, satisfaction degree of patient and loss of working time were recorded. The adverse effects of whole treatment course were recorded. Data were processed with t test. RESULTS: (1) Six months after treatment of 3 times, VSS score of patients was (3.1+/-1.0) points, which was significantly lower than that before the first treatment [(9.4+/-1.8) points, t=53.096, P<0.05]; University of North Carolina Scar Scale score of patients was (1.6+/-0.7) points, which was significantly lower than that before the first treatment[(8.0+/-1.4) points, t=63.730, P<0.05]. (2) Six months after treatment of 3 times, 150 patients were very satisfied with the curative effect, 6 patients were satisfied, and 2 patients were relatively satisfied. The loss of working time of patients was 10-15 (10.5+/-0.3) d. (3) During the treatment, mild erythema appeared in 5 patients which disappeared without treatment; pigmentation appeared in 6 patients 2 weeks after the first treatment, and pruritus and rash appeared in 2 patients 3 days after the first treatment, which were all improved with pharmaceutical therapy. CONCLUSIONS: Ultra pulse mode of ultra pulse carbon dioxide fractional laser combined with Deep FX mode or Scaar FX mode has definitely clinical effect on patients with hypertrophic scars on face and neck with few adverse effects, which is worth to popularize and apply for clinic. PMID- 27562158 TI - [Application of percutaneous transluminal angioplasty in the surgical treatment of patients with diabetic feet]. AB - OBJECTIVE: To explore the application of percutaneous transluminal angioplasty (PTA) in the surgical treatment of patients with diabetic feet. METHODS: The clinical data of 83 patients with diabetic feet, 95 limbs (95 wounds) in total, hospitalized in our unit from September 2011 to September 2014, conforming to the study criteria, were retrospectively analyzed. Patients were divided into conventional treatment group (CT, n=43, 51 wounds) and PTA group (n=40, 44 wounds) according to whether receiving PTA treatment or not. Patients in two groups received conventional debridement after admission, and patients in PTA group received another PTA treatment before debridement. Granulation growing well rates of wounds of patients in two groups were calculated on post debridement day (PDD) 3, 6, 9, and 12. Two stage preoperative preparation time of wounds of patients in two groups was recorded. Status of free skin graft survival of wounds and wound healing of patients in two groups were recorded according to the grade of Wagner. Values of ankle-brachial index (ABI) and ulcer recurrence of patients in two groups checked every month during follow-up time of half a year were recorded. Data were processed with chi-square test and t test. RESULTS: Granulation growing well rate of wounds of patients in group CT rose slowly after treatment, which was less than 40% on PDD 12. Granulation growing well rate of wounds of patients in PTA group rose significantly on PDD 9 and all the granulation grew well on PDD 12. On PDD 9 and 12, Granulation growing well rates of wounds of patients in PTA group were significantly higher than those in group CT (with chi(2) values respectively 30.008 and 47.810, P values below 0.01). Two stage preoperative preparation time of wounds of patients in group CT [(24+/-10) d] was obviously longer than that in PTA group [(15+/-3) d, t=5.709, P<0.01]. The ratios of survived free skin graft and healed suture in Wagner 2, 3, and 4 wounds of patients in PTA group were significantly higher than those in corresponding Wagner of group CT (with chi(2) values from 6.741 to 24.498, P values below 0.01). During follow-up time of half a year, values of ABI of patients in PTA group every month were significantly higher than those in group CT (with t values from 5.411 to 9.583, P values below 0.01). During follow-up time of half a year, there was no ulcer recurrence in group CT in the first four months, but ulcer recurrence was observed in one patient in the fifth month and in two patients in the sixth month. While no ulcer recurrence was found in PTA group during follow up time of half a year. CONCLUSIONS: PTA has certain effect and clinical value for the treatment of diabetic foot. PMID- 27562159 TI - [Classification and corrective methods of obviously asymmetric palpebral fissure of single-fold eyelid]. AB - OBJECTIVE: To discuss the classification of obviously asymmetric palpebral fissure of single-fold eyelid and their corrective methods performed with double fold eyelid blepharoplasty simultaneously. METHODS: Forty patients with obviously asymmetric palpebral fissure of single-fold eyelid of two eyes were admitted to Linyi People's Hospital in Shandong province from January 2010 to September 2014, asking for double-fold eyelid blepharoplasty. The preoperative difference of palpebral fissure width between two eyes reached 1.0-2.0 (1.44+/-0.23) mm. Obviously asymmetric palpebral fissures of single-fold eyelid were divided into three types according to the characteristics of eyelids of two eyes and were corrected by following methods performed with double-fold eyelid blepharoplasty with total incision simultaneously. (1) Twenty-four patients only with different sagging skin of upper eyelids were corrected by resecting sagging skin of eyelids' margins, and the width of the widest position of resected eyelids' skin was twice as wide as that of the sagging skin of eyelids' margins (the same below). (2) Among 6 patients only with different palpebral fissure width, 4 patients whose difference of palpebral fissure width was not bigger than 1.4 mm were corrected by the method of resecting surplus skin, and the width of the widest position of resected eyelids' skin with narrower palpebral fissure was 1 mm wider than the difference of palpebral fissure width between two eyes (the same below). The other 2 patients whose difference of palpebral fissure width between two eyes was bigger than 1.4 mm were corrected by the method of resecting surplus skin and shortening aponeurosis of levator muscle of upper eyelid. The width of shortened aponeurosis of levator muscle of eyelids with narrower palpebral fissure was 1 mm wider than difference of palpebral fissure width between two eyes (the same below). (3) Among 10 patients with mixing symptoms of sagging upper eyelids skin and difference of palpebral fissure width bigger than 1.0 mm after smoothing sagging upper eyelids' skin, 7 patients whose difference of palpebral fissure width was not bigger than 1.4 mm were corrected by resecting sagging skin and the method of resecting surplus skin. The other 3 patients whose difference of palpebral fissure width was bigger than 1.4 mm were corrected by resecting sagging skin, shortening aponeurosis of levator muscle of upper eyelids and resecting surplus skin. Palpebral fissure widths of patients were measured during follow-up. Difference of palpebral fissure width between two eyes was calculated and the last difference was recorded. Data were processed with paired sample t test. RESULTS: Nine patients who showed incomplete closure of palpebral fissure on the sides of resected eyelids skin or shortened aponeurosis of levator muscle of upper eyelids after operations were treated with erythromycin eye ointment drop in eyes and recovered one week to one month after operations, with no complication of conjunctivitis or keratitis. Double-fold eyelids of all patients who were followed up for 8 to 12 months showed natural shape, smooth lines. No patient showed obvious asymmetry of palpebral fissure between two eyes, and no recurrence of asymmetric palpebral fissure was observed. Difference of palpebral fissure width was 0.1-0.5 (0.19+/-0.09) mm in the last follow-up, which was obviously smaller than that before operation (t=39.202, P<0.001). CONCLUSIONS: Obviously asymmetric palpebral fissure of single-fold eyelid can be corrected during the operation of double-fold eyelid blepharoplasty. Patients only with different sagging skin of upper eyelids can be corrected by resecting sagging skin of eyelids' margins. Patients only with different palpebral fissure width between two eyes can be corrected by the method of resecting surplus skin or combining the method of shortening aponeurosis of levator muscle of upper eyelids. Patients with different sagging skin of upper eyelids and different palpebral fissure width can be corrected by resecting sagging skin of eyelids' margins and the method of resecting surplus skin or combining the method of shortening aponeurosis of levator muscle of upper eyelids. PMID- 27562160 TI - [Abnormality in bone metabolism after burn]. AB - Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID- 27562161 TI - [Advances in the research of application of hydrogels in three-dimensional bioprinting]. AB - Hydrogels are three-dimensional networks made of hydrophilic polymer crosslinked through covalent bonds or physical intermolecular attractions, which can contain growth media and growth factors to support cell growth. In bioprinting, hydrogels are used to provide accurate control over cellular microenvironment and to dramatically reduce experimental repetition times, meanwhile we can obtain three dimensional cell images of high quality. Hydrogels in three-dimensional bioprinting have received a considerable interest due to their structural similarities to the natural extracellular matrix and polyporous frameworks which can support the cellular proliferation and survival. Meanwhile, they are accompanied by many challenges. PMID- 27562162 TI - [Advances in the research of acute kidney injury post burn]. AB - Acute kidney injury (AKI), one of the common and important complications post burn, shows a high incidence and mortality in severely burned patients. The common etiologic factors involved in the development of AKI post burn include hypovolaemia, denatured proteins, nephrotoxic agents, etc., while the molecular mechanisms include oxidative stress injury, systematic or local inflammation, apoptosis, and so on. Furthermore, quite a few signaling pathways participate in the regulation of the occurrence and development of AKI post burn. Existed researches on the treatment of AKI post burn focus on the fluid replacement, renal replacement therapy, anti-infection, and specific agents interfering pathophysiologic or molecular mechanisms of AKI. In this review, we summarize the new advances in the research of the occurrence, development, and diagnosis and treatment of AKI post burn. PMID- 27562163 TI - Highly photostable, reversibly photoswitchable fluorescent protein with high contrast ratio for live-cell superresolution microscopy. AB - Two long-standing problems for superresolution (SR) fluorescence microscopy are high illumination intensity and long acquisition time, which significantly hamper its application for live-cell imaging. Reversibly photoswitchable fluorescent proteins (RSFPs) have made it possible to dramatically lower the illumination intensities in saturated depletion-based SR techniques, such as saturated depletion nonlinear structured illumination microscopy (NL-SIM) and reversible saturable optical fluorescence transition microscopy. The characteristics of RSFPs most critical for SR live-cell imaging include, first, the integrated fluorescence signal across each switching cycle, which depends upon the absorption cross-section, effective quantum yield, and characteristic switching time from the fluorescent "on" to "off" state; second, the fluorescence contrast ratio of on/off states; and third, the photostability under excitation and depletion. Up to now, the RSFPs of the Dronpa and rsEGFP (reversibly switchable EGFP) families have been exploited for SR imaging. However, their limited number of switching cycles, relatively low fluorescence signal, and poor contrast ratio under physiological conditions ultimately restrict their utility in time-lapse live-cell imaging and their ability to reach the desired resolution at a reasonable signal-to-noise ratio. Here, we present a truly monomeric RSFP, Skylan NS, whose properties are optimized for the recently developed patterned activation NL-SIM, which enables low-intensity (~100 W/cm(2)) live-cell SR imaging at ~60-nm resolution at subsecond acquisition times for tens of time points over broad field of view. PMID- 27562164 TI - Prediction of multidimensional drug dose responses based on measurements of drug pairs. AB - Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments. PMID- 27562165 TI - Interplay between hydrophobicity and the positive-inside rule in determining membrane-protein topology. AB - The energetics of membrane-protein interactions determine protein topology and structure: hydrophobicity drives the insertion of helical segments into the membrane, and positive charges orient the protein with respect to the membrane plane according to the positive-inside rule. Until recently, however, quantifying these contributions met with difficulty, precluding systematic analysis of the energetic basis for membrane-protein topology. We recently developed the dsTbetaL method, which uses deep sequencing and in vitro selection of segments inserted into the bacterial plasma membrane to infer insertion-energy profiles for each amino acid residue across the membrane, and quantified the insertion contribution from hydrophobicity and the positive-inside rule. Here, we present a topology prediction algorithm called TopGraph, which is based on a sequence search for minimum dsTbetaL insertion energy. Whereas the average insertion energy assigned by previous experimental scales was positive (unfavorable), the average assigned by TopGraph in a nonredundant set is -6.9 kcal/mol. By quantifying contributions from both hydrophobicity and the positive-inside rule we further find that in about half of large membrane proteins polar segments are inserted into the membrane to position more positive charges in the cytoplasm, suggesting an interplay between these two energy contributions. Because membrane-embedded polar residues are crucial for substrate binding and conformational change, the results implicate the positive-inside rule in determining the architectures of membrane protein functional sites. This insight may aid structure prediction, engineering, and design of membrane proteins. TopGraph is available online (topgraph.weizmann.ac.il). PMID- 27562166 TI - Deconstructing the winding path to the recapitulation of mammalian oogenesis ex vivo. PMID- 27562167 TI - NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA. AB - Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host-pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches. PMID- 27562168 TI - Histone deacetylase HDA6 enhances brassinosteroid signaling by inhibiting the BIN2 kinase. AB - Glycogen synthase kinase 3 (GSK3)-like kinases play important roles in brassinosteroid (BR), abscisic acid, and auxin signaling to regulate many aspects of plant development and stress responses. The Arabidopsis thaliana GSK3-like kinase BR-INSENSITIVE 2 (BIN2) acts as a key negative regulator in the BR signaling pathway, but the mechanisms regulating BIN2 function remain unclear. Here we report that the histone deacetylase HDA6 can interact with and deacetylate BIN2 to repress its kinase activity. The hda6 mutant showed a BR repressed phenotype in the dark and was less sensitive to BR biosynthesis inhibitors. Genetic analysis indicated that HDA6 regulates BR signaling through BIN2. Furthermore, we identified K189 of BIN2 as an acetylated site, which can be deacetylated by HDA6 to influence BIN2 activity. Glucose can affect the acetylation level of BIN2 in plants, indicating a connection to cellular energy status. These findings provide significant insights into the regulation of GSK3 like kinases in plant growth and development. PMID- 27562169 TI - Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate. AB - Many secretory tissues release Zn(II) ions along with other molecules in response to external stimuli. Here we demonstrate that secretion of Zn(II) ions from normal, healthy prostate tissue is stimulated by glucose in fasted mice and that release of Zn(II) can be monitored by MRI. An ~50% increase in water proton signal enhancement is observed in T1-weighted images of the healthy mouse prostate after infusion of a Gd-based Zn(II) sensor and an i.p. bolus of glucose. Release of Zn(II) from intracellular stores was validated in human epithelial prostate cells in vitro and in surgically exposed prostate tissue in vivo using a Zn(II)-sensitive fluorescent probe known to bind to the extracellular surface of cells. Given the known differences in intracellular Zn(II) stores in healthy versus malignant prostate tissues, the Zn(II) sensor was then evaluated in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model in vivo. The agent proved successful in detecting small malignant lesions as early as 11 wk of age, making this noninvasive MR imaging method potentially useful for identifying prostate cancer in situations where it may be difficult to detect using current multiparametric MRI protocols. PMID- 27562171 TI - Prediction of Clearance, Volume of distribution, and Half-life of Drugs in Extremely Low to Low Birth Weight Neonates: An Allometric Approach. AB - BACKGROUND AND OBJECTIVES: More than 20 million infants worldwide (15.5 % of all births) are born with low birth weight. Low birth weight is associated with poor growth in childhood and a higher incidence of adult diseases, such as type 2 diabetes, hypertension and cardiovascular disease. The objective of this study was to evaluate the predictive performance of allometric models to predict clearance, volume of distribution, and half-life in extremely low to low birth weight neonates (<1 to 2.5 kg body weight). METHODS: Several allometric models were used to predict clearance (4 models), volume of distribution (2 models), and half-life (2 models) in extremely low to low birth weight neonates. From the literature, clearance, volume of distribution, and half-life values for 16 drugs for these neonates were obtained. The predictive performance of these allometric models was evaluated by comparing the predicted values of the aforementioned pharmacokinetic parameters with the observed pharmacokinetic parameters in an individual neonate. For the evaluation of the predictive performance of these allometric models, there were 16 drugs with 36 (n = 279), 34 (n = 261), and 31 (n = 197) weight groups for clearance, volume of distribution, and half-life, respectively. RESULTS: The prediction error of <=50 % for mean clearance, volume of distribution, and half-life values were 69, 79, and 58 %, respectively, by proposed allometric models. The prediction error of <=50 % for mean clearance, volume of distribution, and half-life values by theoretical allometric exponents were 0 % (exponent = 0.75), 71 % (exponent = 1.0), and 0 % (exponent = 0.25), respectively. In this analysis, out of 16 drugs, there were three drugs (ibuprofen, zidovudine, and buprenorphine) which are metabolized by glucuronidation and one drug (furosemide) is renally secreted. The predicted clearances of these four drugs were substantially higher by the proposed allometric methods. It seems that drugs of these physiological characteristics may require different method(s) to improve the prediction of clearance in the neonates. CONCLUSIONS: Overall, the proposed allometric methods can predict mean pharmacokinetic parameters of drugs in extremely low to low birth weight neonates with reasonable accuracy and are of practical value during neonatal drug development. PMID- 27562170 TI - Na+ coordination at the Na2 site of the Na+/I- symporter. AB - The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid the first step in thyroid hormone biosynthesis-with a 2 Na(+): 1 I(-) stoichiometry. The two Na(+) binding sites (Na1 and Na2) and the I(-) binding site interact allosterically: when Na(+) binds to a Na(+) site, the affinity of NIS for the other Na(+) and for I(-) increases significantly. In all Na(+) dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na(+) ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues-S66, D191, Q194, and Q263-are also involved in Na(+) coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I(-) These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance. PMID- 27562172 TI - Evolutionary and immediate effects of crude-oil pollution: depression of exploratory behaviour across populations of Trinidadian guppies. AB - Human-induced perturbations such as crude-oil pollution can pose serious threats to aquatic ecosystems. To understand these threats fully it is important to establish both the immediate and evolutionary effects of pollutants on behaviour and cognition. Addressing such questions requires comparative and experimental study of populations that have evolved under different levels of pollution. Here, we compared the exploratory, activity and social behaviour of four populations of Trinidadian guppies (Poecilia reticulata) raised in common garden conditions for up to three generations. Two of these populations originated from tributaries with a long history of human-induced chronic crude-oil pollution with polycyclic aromatic hydrocarbons due to oil exploitation in Trinidad, the two others originating from non-polluted control sites. Laboratory-raised guppies from the oil-polluted sites were less exploratory in an experimental maze than guppies from the non-polluted sites and in a similar manner for the two independent rivers. We then compared the plastic behavioural responses of the different populations after an acute short-term experimental exposure to crude oil and found a decrease in exploration (but not in activity or shoaling) in the oil exposed fish compared to the control subjects over all four populations. Taken together, these results suggest that both an evolutionary history with oil and an acute exposure to oil depressed guppy exploratory behaviour. We discuss whether the behavioural divergence observed represents adaptation to human-induced pollutants, the implications for conservation and the possible knock-on effects for information discovery and population persistence in fish groups. PMID- 27562173 TI - Upregulation of cyclin-dependent kinase 7 and matrix metalloproteinase-14 expression contribute to metastatic properties of gastric cancer. AB - The aim of this study was to evaluate the protein and mRNA expressions of matrix metalloproteinase-14 (MMP14) and CDK7 in gastric cancer (GC) tissues. Upregulation of MMP14 mRNA level was observed in GC tissues when compared with the matched normal tissues (mean +/- SD: 3.92 +/- 1.15 vs. 1.35 +/- 0.81, P < 0.001). This study indicated that mRNA levels of CDK7 were statistically overexpressed in GC when compared with matched normal tissues (4.12 +/- 0.84 vs. 1.43 +/- 0.71, P < 0.001). The protein levels of MMP14 were found to be increased in GC (60.41%; P < 0.001). The expression of CDK7 was higher in GC tissues than matched normal tissues (70.83; P < 0.001). We found that high MMP14 expression was related to advanced TNM stage (P = 0.004), tumor grade (P = 0.002), and lymph node metastasis (P = 0.015), but no association with other clinical variables (P > 0.05). In addition, high expression of CDK7 was significantly linked to advanced TNM stage (P = 0.001), pathological grade (P = 0.012), and presence of lymph node metastasis (P = 0.009), while no correlation between CDK7 expression and other clinical variables, such as age and gender, distance metastasis. The patients with high expression of MMP14 and CDK7 exhibited worse survival time than those with higher levels. Cox multivariate regression analysis clearly showed that high expression of MMP14 and CDK7 was independent prognostic factors for overall survival in patients with GC. Taken together, these results indicated the overexpression of above markers in the progression and the tumorigenesis of GC and overall patient survival. (c) 2016 IUBMB Life, 68(10):799-805, 2016. PMID- 27562174 TI - Role of echocardiography before cardiac resynchronization therapy: new advances and current developments. AB - The role of echocardiography in improving the selection of patients who will benefit from cardiac resynchronization therapy (CRT) remains a source of debate. Although previous landmark reports have demonstrated a link between mechanical dyssynchrony, assessed by delays between left ventricle (LV) walls and response to CRT, the predictive value of these findings has not yet been confirmed in multicenter trials. Indeed, recent studies demonstrated that the classical assessment of LV mechanical dyssynchrony using delay between walls by echocardiography depends not only on LV electrical activation delay (electrical dyssynchrony), but also on abnormalities in regional contractility of the LV and/or loading conditions, which do not represent an appropriate target for CRT. Recent reports highlighted the value of new indices of electromechanical dyssynchrony obtained by echocardiography, to predict LV response and outcome after CRT including septal flash, left bundle branch block-typical pattern by longitudinal strain, apical rocking, septal strain patterns, and systolic stretch index. This was achieved using a mechanistic approach, based on the contractile consequences of electrical dyssynchrony. These indices are rarely found in patients with narrow QRS (<120 ms), whereas their frequency rises in patients with an increase in QRS duration (>120 ms). Theses indices should improve candidate selection for CRT in clinical practice, especially for patients in whom the benefit of CRT remains uncertain, for example, patients with intermediate QRS width (120-150 ms). PMID- 27562175 TI - Aggressive Event Incidence using the Staff Observation of Aggression Scale Revised (SOAS-R): A Longitudinal Study. AB - The aim of this study was to identify aggressive event incidence rates in the inpatient psychiatric setting, describe characteristics of events and differences based on aggression target and type (verbal vs. physical). A longitudinal study was carried out of aggressive events identified by workers in four inpatient psychiatric units using the Staff Observation of Aggression Scale-Revised (SOAS R) over 6 weeks. A total of 113 aggressive events were recorded resulting in a rate of 13.27 events per bed per year. Verbal aggression was demonstrated in 86 % and physical aggression in 57 % of events. Most events (70.8 %, n = 81) targeted a worker. Compared to other targets, workers were 3.4 times more likely to feel threatened (95 % CI 1.2-9.6, chi2 = 5.08, p = 0.0242), and less likely to have a visible injury (OR 0.15, 95 % CI 0.04-0.6; chi2 = 7.1, p = 0.0078). Event severity ranged from 0 to 21 with a mean of 9.5(SD = 5.1), with 20 % considered severe. Verbal events had lower mean severity of 6.5(SD = 3.8) versus physical events with a severity of 11.8(SD = 4.8; t = 6.5, df = 111, p < 0.0001). In 57.5 % of events there was no consequence to the victim. For most events (76 %) resolution included workers talking to the patient, while 54 % involved use of medication. Restrictive measures (physical hold, seclusion or physical restraint) were involved in 24.8 % of events. Aggression incidence was similar to incidence found in other studies. Workers were the target of most aggressive events and many were identified as having no understandable provocation. Further understanding of event characteristics will promote more effective prevention and management of aggressive events. PMID- 27562177 TI - In allergic rhinitis, work, classroom and activity impairments are weakly related to other outcome measures. AB - BACKGROUND: The impact of grass pollen-induced allergic rhinitis (AR) on classroom/work productivity and activities can be assessed with a specific instrument: the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI-AS). This study evaluated the relationships between the WPAI-AS and other outcome measures in AR. METHODS: Adolescents (aged 12-17) and adults (aged 18-65) consulting specialists for AR were enrolled in a four-week, multicentre, observational study. The management of AR was left to the physicians' discretion. Participants regularly rated the WPAI AS, their symptoms (using the Rhinoconjunctivitis Total Symptom Score (RTSS) and a 0- to 100-mm visual analogue scale (VAS)) and quality of life (according to the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)). RESULTS: A total of 247 adolescents and 292 adults showed similar baseline impairments in classroom/work productivity and activities other than work. In both age groups, the WPAI-AS scores were moderately correlated with the RQLQ score and, to a lesser extent, with the VAS score and the RTSS. A multiple regression analysis indicated that the RQLQ score was a weak but statistically significant predictor of both impaired work/classroom productivity and daily activities. A 50-mm VAS cut-off categorized patients in whom AR had the greatest impact on productivity. CONCLUSIONS: Grass pollen-induced AR impairs work/classroom and daily activity to a similar extent in adults and adolescents. The weak-to-moderate correlations with AR symptom scores and quality-of-life scores suggest that a specific tool (such as the WPAI-AS) should be used to assess AR's impact on word/classroom productivity and daily activities. PMID- 27562176 TI - A novel mass spectrometric strategy "BEMAP" reveals Extensive O-linked protein glycosylation in Enterotoxigenic Escherichia coli. AB - The attachment of sugars to proteins via side-chain oxygen atoms (O-linked glycosylation) is seen in all three domains of life. However, a lack of widely applicable analytical tools has restricted the study of this process, particularly in bacteria. In E. coli, only four O-linked glycoproteins have previously been characterized. Here we present a glycoproteomics technique, termed BEMAP, which is based on the beta-elimination of O-linked glycans followed by Michael-addition of a phosphonic acid derivative, and subsequent titanium dioxide enrichment. This strategy allows site-specific mass-spectrometric identification of proteins with O-linked glycan modifications in a complex biological sample. Using BEMAP we identified cell surface-associated and membrane vesicle glycoproteins from Enterotoxigenic E. coli (ETEC) and non-pathogenic E. coli K-12. We identified 618 glycosylated Serine and Threonine residues mapping to 140 proteins in ETEC, including several known virulence factors, and 34 in E. coli K-12. The two strains had 32 glycoproteins in common. Remarkably, the majority of the ETEC glycoproteins were conserved in both strains but nevertheless were only glycosylated in the pathogen. Therefore, bacterial O linked glycosylation is much more extensive than previously thought, and is especially important to the pathogen. PMID- 27562179 TI - Proteome Analysis of Potential Synaptic Vesicle Cycle Biomarkers in the Cerebrospinal Fluid of Patients with Sporadic Creutzfeldt-Jakob Disease. AB - Sporadic Creutzfeldt-Jakob disease (sCJD) is the most frequent fatal human prion disease with a rapid progression and unknown mechanism. The synaptic vesicle (SV) cycle pathway has been a hot research field associated with many neurodegenerative diseases that affect synaptic function and thus may affect pathogenesis of the disorder. Here, we used the iTRAQ-based proteomic method and a KEGG pathway enrichment analysis to meticulously analyze all pathways involved in sCJD disease. In total, 1670 proteins were validated in pooled cerebrospinal fluid (CSF) from 20 patients with sCJD compared with that from 13 patients without CJD. The demographic analysis demonstrated that 557 proteins were upregulated and 595 proteins were downregulated with a 1.5-fold change, and 690 proteins involved in 39 pathways changed significantly (p <= 0.05) according to the enrichment analysis. The SV cycle pathway and proteins involved were further evaluated, and 14 proteins were confirmed to participate in the SV cycle pathway due to increased expression. Six key proteins, such as AP2A1, SYT1, SNAP25, STXBP1, CLTB, and Rab3a, showed the same trend by western blot as detected by iTRAQ. This is the first study to use high-throughput proteomics to accurately identify and quantify proteins in the SV cycle pathway of a neurodegenerative disease. These results will help define the mechanism and provide new insight into the pathogenetic factors involved in the SV cycle pathway in patients with sCJD. We hope that promising biomarkers can be identified in the CSF of patients with sCJD and other neurodegenerative disorders to help predict disease progression. PMID- 27562178 TI - Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1. AB - Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta = 5.72 * 10-4), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 * 10-16). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a "proxy phenotype" of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ~1.2 Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis. PMID- 27562180 TI - Rare Genetic Variants of the Transthyretin Gene Are Associated with Alzheimer's Disease in Han Chinese. AB - Alzheimer's disease (AD) is the most prevalent form of dementia in the world. The neuropathological characteristics of AD patients are the accumulation of extracellular plaques of beta-amyloid (Abeta) and intracellular hyperphosphorylated tau protein. Transthyretin (TTR) may alleviate AD symptom by reducing Abeta concentration in the brain. There were reports for a decreased TTR level in both AD brain and blood. However, there is still no robust evidence to support the genetic association of the TTR gene with AD. In this study, we aimed to investigate the potential association of TTR variation with AD by directly sequencing the whole exons and the promoter region of the TTR gene in 529 AD patients and 334 healthy controls from Han Chinese population. We found no association between TTR common variants and AD but observed an enrichment of TTR rare variants in AD patients relative to controls. Further in silico prediction analysis and functional assessment at the cellular level identified four potentially pathogenic rare variants in AD patients. In particular, variant c. 239C>A could potentially downregulate the TTR promoter activity; c.200+4A>G might influence the constitutive splicing of TTR mRNA; c.148G>A (p.V50M) and c.332C>T (p.A111V) would change the structure of TTR and decrease its Abeta-binding ability. Our results provided direct genetic evidence to support the active involvement of TTR in AD. PMID- 27562182 TI - Understanding the role of religious views in the discussion about resuscitation at the threshold of viability. PMID- 27562181 TI - A new experimentally validated formula to calculate the QT interval in the presence of left bundle branch block holds true in the clinical setting. AB - BACKGROUND: The evaluation of the QT interval in the presence of left bundle branch block (LBBB) is associated with the challenge to discriminate native QT interval from the prolongation due to the increase in QRS duration. The newest formula to evaluate QT interval in the presence of LBBB suggests: modified QT during LBBB = measured QT interval minus 50% of LBBB duration. The purpose of this study is therefore to validate the abovementioned formula in the clinical setting. METHODS: Validation in two separate groups of patients: Patients who alternated between narrow QRS and intermittent LBBB and patients with narrow QRS who developed LBBB after transcatheter aortic valve implantation (TAVI). RESULTS: The acquired mean native QTc intervals and those calculated by the presented formula displayed no significant differences (p > .99 and p > .75). CONCLUSIONS: In this study we proved for the first time the validity and applicability of the experimentally acquired formula for the evaluation of the QT interval in the presence of LBBB in a clinical setting. PMID- 27562183 TI - Targeting supernormal frequencies and very low tidal volumes in high-frequency oscillatory ventilation: can 'volume guarantee' deliver? PMID- 27562184 TI - Response to "Targeting supernormal frequencies and very low tidal volumes in high frequency oscillatory ventilation: can 'volume guarantee' deliver?". PMID- 27562185 TI - Assessment of endotracheal tube placement in newborn infants: a randomized controlled trial. PMID- 27562186 TI - Pro and con: Internal speech and the evolution of complex language. AB - The target article by Christiansen & Chater (C&C) offers an integrated framework for the study of language acquisition and, possibly, a novel role for internal speech in language acquisition. However, the "Now-or-Never bottleneck" raises a paradox for language evolution. It seems to imply that language complexity has been either reduced over time or has remained the same. How, then, could languages as complex as ours have evolved in prelinguistic ancestors? Linguistic Platonism could offer a solution to this paradox. PMID- 27562187 TI - Development of a voltage-dependent current noise algorithm for conductance-based stochastic modelling of auditory nerve fibres. AB - This study presents the development of an alternative noise current term and novel voltage-dependent current noise algorithm for conductance-based stochastic auditory nerve fibre (ANF) models. ANFs are known to have significant variance in threshold stimulus which affects temporal characteristics such as latency. This variance is primarily caused by the stochastic behaviour or microscopic fluctuations of the node of Ranvier's voltage-dependent sodium channels of which the intensity is a function of membrane voltage. Though easy to implement and low in computational cost, existing current noise models have two deficiencies: it is independent of membrane voltage, and it is unable to inherently determine the noise intensity required to produce in vivo measured discharge probability functions. The proposed algorithm overcomes these deficiencies while maintaining its low computational cost and ease of implementation compared to other conductance and Markovian-based stochastic models. The algorithm is applied to a Hodgkin-Huxley-based compartmental cat ANF model and validated via comparison of the threshold probability and latency distributions to measured cat ANF data. Simulation results show the algorithm's adherence to in vivo stochastic fibre characteristics such as an exponential relationship between the membrane noise and transmembrane voltage, a negative linear relationship between the log of the relative spread of the discharge probability and the log of the fibre diameter and a decrease in latency with an increase in stimulus intensity. PMID- 27562188 TI - The cooperative breeding perspective helps in pinning down when uniquely human evolutionary processes are necessary. AB - The cultural group selection (CGS) approach provides a compelling explanation for recent changes in human societies, but has trouble explaining why our ancestors, rather than any other great ape, evolved into a hyper-cooperative niche. The cooperative breeding hypothesis can plug this gap and thus complement CGS, because recent comparative evidence suggests that it promoted proactive prosociality, social transmission, and communication in Pleistocene hominins. PMID- 27562189 TI - Standardizing patient outcomes measurement to improve haemophilia care. PMID- 27562190 TI - Sedentary bout durations and metabolic syndrome among working adults: a prospective cohort study. AB - BACKGROUND: This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome. METHODS: We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having >= 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated >= 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome. RESULTS: During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 - 5.73), 2.42 (1.11 - 5.50), and 2.85 (1.31 - 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts. CONCLUSIONS: Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered. PMID- 27562191 TI - IL-33-driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity. AB - Group 2 innate lymphoid cells (ILC2s) in white adipose tissue (WAT) promote WAT browning and assist in preventing the development of obesity. However, how ILC2 in adipose tissue is regulated remains largely unknown. Here, our study shows that ILC2s are present in brown adipose tissue (BAT) as well as subcutaneous and epididymal WAT (sWAT and eWAT). The fractions of ILC2s, natural killer T (NKT) cells and eosinophils in sWAT, eWAT and BAT are significantly decreased by high fat-diet (HFD) feeding and leptin deficiency-induced obesity. Consistent with this, the adipose expression and circulating levels of IL-33, a key inducing cytokine of ILC2, are significantly downregulated by obesity. Furthermore, administration of IL-33 markedly increases the fraction of ILC2 and eosinophil as well as the expression of UCP1 and tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, in adipose tissue of HFD-fed mice. On the other hand, cold exposure induces the expression levels of IL-33 and UCP1 and the population of ILC2 and eosinophil in sWAT, and these promoting effects of cold stress are reversed by neutralization of IL-33 signaling in vivo Moreover, the basal and cold-induced IL-33 and ILC2/eosinophil pathways are significantly suppressed by sympathetic denervation via local injection of 6-hydroxydopamine (6 OHDA) in sWAT. Taken together, our data suggest that the ILC2/eosinophil axis in adipose tissue is regulated by sympathetic nervous system and obesity in IL-33 dependent manner, and IL-33-driven ILC2/eosinophil axis is implicated in the development of obesity. PMID- 27562193 TI - Autonomy in ants and humans. AB - Drawing lessons regarding the consequences of ultrasociality in ants and humans depends crucially on recognizing differences as well as similarities in the way that species are social. We focus on Gowdy & Krall's use of the concept of autonomy to explicate essential differences in the ways in which ants and humans are social. PMID- 27562192 TI - Water-, pH- and temperature relations of germination for the extreme xerophiles Xeromyces bisporus (FRR 0025), Aspergillus penicillioides (JH06THJ) and Eurotium halophilicum (FRR 2471). AB - Water activity, temperature and pH are determinants for biotic activity of cellular systems, biosphere function and, indeed, for all life processes. This study was carried out at high concentrations of glycerol, which concurrently reduces water activity and acts as a stress protectant, to characterize the biophysical capabilities of the most extremely xerophilic organisms known. These were the fungal xerophiles: Xeromyces bisporus (FRR 0025), Aspergillus penicillioides (JH06THJ) and Eurotium halophilicum (FRR 2471). High-glycerol spores were produced and germination was determined using 38 media in the 0.995 0.637 water activity range, 33 media in the 2.80-9.80 pH range and 10 incubation temperatures, from 2 to 50 degrees C. Water activity was modified by supplementing media with glycerol+sucrose, glycerol+NaCl and glycerol+NaCl+sucrose which are known to be biologically permissive for X. bisporus, A. penicillioides and E. halophilicum respectively. The windows and rates for spore germination were quantified for water activity, pH and temperature; symmetry/asymmetry of the germination profiles were then determined in relation to supra- and sub-optimal conditions; and pH- and temperature optima for extreme xerophilicity were quantified. The windows for spore germination were ~1 to 0.637 water activity, pH 2.80-9.80 and > 10 and < 44 degrees C, depending on strain. Germination profiles in relation to water activity and temperature were asymmetrical because conditions known to entropically disorder cellular macromolecules, i.e. supra-optimal water activity and high temperatures, were severely inhibitory. Implications of these processes were considered in relation to the in-situ ecology of extreme conditions and environments; the study also raises a number of unanswered questions which suggest the need for new lines of experimentation. PMID- 27562194 TI - Coping strategies and the Salutogenic Model in future oral health professionals. AB - BACKGROUND: Attention to the role of context in shaping individuals' coping strategies is necessary. This study used the Salutogenic Model (SM) as a framework to identify the coping strategies of oral health profession students from three countries. METHODS: Students from Australia, New Zealand and Chile were invited to participate in this cross-sectional study, and were given a questionnaire including socio-demographics, the Perceived Stress Scale, The SOC 13 and the Brief COPE. Descriptive analysis, correlation analysis and profile analysis were computed using SPSS v 20.0. RESULTS: Eight-hundred and ninety-seven valid questionnaires were returned, achieving a 44 % response rate. The coping dimension that the participants most commonly reported using was "Active Coping" with a mean value of 5.9 +/- 1.5. Chilean respondents reported higher stress levels (19.8 vs. 17.7) and a lower Sense of Coherence (55.6 vs. 58.0) compared to Australian/New Zealand participants (p < 0.001). The SOC was positively correlated with active coping (p < 0.01) and positive reframing (p < 0.01). Profile analysis showed that when the differences in responses by sex were accounted for, there was no significant effect by country on the coping strategies used (p < 0.32). CONCLUSION: This initial investigation provides insights into the students' coping strategies and the validity of the SM. Students reporting high SOC scores where those who demonstrated the use of active coping and positive reframing as strategies to deal with stressful situations, which indicates the accuracy of the theoretical framework of the SM in health education environments. The results also suggest that a distinctive coping strategy pattern may apply to all participants, regardless of their country and sex. PMID- 27562195 TI - The contribution of inferior colliculus activity to the auditory brainstem response (ABR) in mice. AB - In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P0 with peak latency 7-8 ms when recorded with adequate band-pass filtering. Wave P0 showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P0 in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV. PMID- 27562196 TI - Relationship between ecomorphology and trophic segregation in four closely related sympatric fish species (Teleostei, Sciaenidae). AB - This study explores the relationship between ecomorphology and trophic segregation in four closely related sympatric fish species (Teleostei, Sciaenidae) that are known to differ in their trophic habits. Only adult specimens were analyzed: 103 Cynoscion guatucupa, 77 Pogonias cromis, 61 Micropogonias furnieri, and 48 Menticirrhus americanus. The four species presented divergent ecomorphological traits related to swimming agility, prey spotting and capture, and the potential size of prey they were able to swallow. Results suggest that these sciaenid species can partition the food resources, even though they completely overlap in space. Differences in their ecomorphological traits appear to correlate closely with the diet and consequently could explain the trophic differentiation observed. Arguably, these ecomorphological differences play a significant role in the coexistence of the adults of these sympatric fish species. PMID- 27562197 TI - Neurocognitive performance following acute mephedrone administration, with and without alcohol. AB - Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters. PMID- 27562198 TI - The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants? AB - +/-3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that enhances sociability and feelings of closeness with others. These "prosocial" effects appear to motivate the recreational use of MDMA and may also form the basis of its potential as an adjunct to psychotherapy. However, the extent to which MDMA differs from prototypic stimulant drugs, such as dextroamphetamine, methamphetamine, and methylphenidate, in either its behavioral effects or mechanisms of action, is not fully known. The purpose of this review is to evaluate human laboratory findings of the social effects of MDMA compared to other stimulants, ranging from simple subjective ratings of sociability to more complex elements of social processing and behavior. We also review the neurochemical mechanisms by which these drugs may impact sociability. Together, the findings reviewed here lay the groundwork for better understanding the socially enhancing effects of MDMA that distinguish it from other stimulant drugs, especially as these effects relate to the reinforcing and potentially therapeutic effects of the drug. PMID- 27562199 TI - On the generalizability of the Chunk-and-Pass processing approach: Perspectives from language acquisition and music. AB - Christiansen & Chater (C&C) offer the Chunk-and-Pass strategy as a language processing approach allowing humans to make sense of incoming language in the face of cognitive and perceptual constraints. We propose that the Chunk-and-Pass strategy is not adequate to extend universally across languages (accounting for typologically diverse languages), nor is it sufficient to generalize to other auditory modalities such as music. PMID- 27562200 TI - A Plea for the Development of New Benign Prostatic Obstruction Follow-up Guidelines. PMID- 27562201 TI - Reply by the Authors. PMID- 27562202 TI - Risk Stratification by Urinary Prostate Cancer Gene 3 Testing Before Magnetic Resonance Imaging-Ultrasound Fusion-targeted Prostate Biopsy Among Men With No History of Biopsy. AB - OBJECTIVE: To determine whether a combination of prostate cancer gene 3 (PCA3) and magnetic resonance imaging (MRI) suspicion score (mSS) could further optimize detection of prostate cancer on MRI fusion-targeted biopsy (MRF-TB) among men with no history of biopsy. MATERIALS AND METHODS: We included in this study 187 men presenting to our institution between June 2012 and August 2014 who underwent multiparametric MRI (mpMRI) and PCA3 before MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics curves and multivariable logistic regressions were used to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS: PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (area under the curve: 0.67, 95% confidence interval: 0.59-0.76). Using a cutoff of >=35, PCA3 was associated with cancer risk among men with mSS 2-3 (P = .004), but not among those with mSS 4-5 (P = .340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (area under the curve: 0.83 vs 0.79, P = .0434). CONCLUSION: Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high-suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB, adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI. PMID- 27562203 TI - Splenogonadal Fusion Presenting as an Asymptomatic Testicular Mass. PMID- 27562204 TI - Diphallia in the Ancient World: Insights From a Pompeian Fresco (70-79 AD). PMID- 27562205 TI - When Physical Examination Signs Point to Sinister Causes. AB - A 55-year-old male presented with mild abdominal discomfort. On physical examination, a right upper quadrant abdominal mass was palpable and an obstructed right varicocele was evident. Ultrasonography and computed tomography revealed a 15 cm right renal tumor with a 2 cm aortocaval lymph node. The patient underwent an uneventful laparoscopic transperitoneal radical nephrectomy and lymphadenectomy and was discharged after 2 days. No complications or recurrence were noted at 6 months follow-up. This report signifies the importance of physical examination and attention to cardinal clinical signs and also the feasibility of laparoscopy in large renal tumor in expert hands. PMID- 27562206 TI - Role of Technology for the Management of AKI in Critically Ill Patients: From Adoptive Technology to Precision Continuous Renal Replacement Therapy. AB - This paper reports on the continuous renal replacement therapy (CRRT) technology group recommendations and research proposals developed during the 17th Acute Dialysis Quality Initiative Meeting in Asiago, Italy. The group was tasked to address questions related to the impact of technology on acute kidney injury management. We discuss technological aspects of the decision to initiate CRRT and the components of the treatment prescription and delivery, the integration of information technology (IT) on overall patient management, the incorporation of CRRT into other 'non-renal' extracorporeal technologies such as ECMO and ECCO2R and the use of sorbents in sepsis and propose new areas for future research. Instead of reviewing current knowledge, the group focused on developing a renovated research agenda that reflects current and future technological advances, centered on innovations in new equipment, membranes and IT that will permit the integration of patient care and decision-making processes for years to come. PMID- 27562207 TI - Host sanctions in Panamanian Ficus are likely based on selective resource allocation. AB - PREMISE OF THE STUDY: Fig trees and their pollinators, fig wasps, present a powerful model system for studying mutualism stability: both partners depend on each other for reproduction, cooperation levels can be manipulated, and the resulting field-based fitness quantified. Previous work has shown that fig trees can severely reduce the fitness of wasps that do not pollinate by aborting unpollinated figs or reducing the number and size of wasp offspring. Here we evaluated four hypotheses regarding the mechanism of sanctions in four Panamanian fig species. METHODS: We examined wasp and fig samples from field experiments with manipulated levels of pollination. KEY RESULTS: In unpollinated figs, the fig wall and the wasp offspring had a lower dry mass. Unpollinated figs had as many initiated wasp galls as pollinated figs but fewer galls that successfully produced live wasp offspring. Across three experimentally increasing levels of pollination, we found nonlinear increases in fig wall mass, the proportion of wasp galls that develop, and wasp mass. CONCLUSIONS: Our data did not support the hypotheses that lack of pollination prevents gall formation or that fertilized endosperm is required for wasp development. While our data are potentially consistent with the hypothesis that trees produce a wasp-specific toxin in response to lack of pollination, we found the hypothesis that sanctions are a consequence of trees allocating more resources to better-pollinated figs more parsimonious with the aggregate data. Our findings are completely analogous to the selective resource allocation to more beneficial tissues documented in other mutualistic systems. PMID- 27562208 TI - Enhanced rhizobial symbiotic capacity in an allopolyploid species of Glycine (Leguminosae). AB - PREMISE OF THE STUDY: Previous studies have shown that polyploidy can alter biotic interactions, and it has been suggested that these effects may contribute to the increased ability for colonization of new habitats shown by many allopolyploids. Little is known, however, about the effects of allopolyploidy, which combines hybridity and genome doubling, on symbiotic interactions with rhizobial bacteria. METHODS: We examined interactions of the allopolyploid Glycine dolichocarpa (designated T2) with novel rhizobial partners, such as might occur in a context of colonization, and compared these with the responses of its diploid progenitors, G. tomentella (D3) and G. syndetika (D4). We assessed root hair response, nodule formation, nodule mass, nodule number, and plant biomass. KEY RESULTS: The allopolyploid (T2) showed a greater root hair deformation response when exposed to rhizobia, compared with either diploid. T2 had a greater probability of forming nodules with NGR234 compared with diploid D4, and greater total nodule mass per nodulated plant compared with diploid D3. T2 also had greater plant biomass responses to nitrogen and when exposed to NGR234. CONCLUSIONS: The allopolyploid is characterized by transgressive responses to rhizobia for some variables, while also combining certain parental diploid responses such that its capacity for interactions with rhizobia appears to be greater than for either diploid progenitor. This overall enhanced nodulation capacity and the ability to make greater gains from exposure to both rhizobia and additional nitrogen indicate a greater potential of the allopolyploid to benefit from these factors both generally and in a context of colonization. PMID- 27562209 TI - Type I Pleuropulmonary Blastoma versus Congenital Pulmonary Airway Malformation Type IV. PMID- 27562210 TI - Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture. AB - Hepatitis C virus (HCV) infection is a major biomedical problem worldwide. Although new direct antiviral agents (DAAs) have been developed for the treatment of chronic HCV infection, the potential emergence of resistant virus variants and the difficulties to implement their administration worldwide make the development of novel antiviral agents an urgent need. Moreover, no effective vaccine is available against HCV and transmission of the virus still occurs particularly when prophylactic measures are not taken. We used a cell-based system to screen a battery of polyanionic carbosilane dendrimers (PCDs) to identify compounds with antiviral activity against HCV and show that they inhibit effective virus adsorption of major HCV genotypes. Interestingly, one of the PCDs irreversibly destabilized infectious virions. This compound displays additive effect in combination with a clinically relevant DAA, sofosbuvir. Our results support further characterization of these molecules as nanotools for the control of hepatitis C virus spread. PMID- 27562211 TI - Osteotropic nanoscale drug delivery systems based on small molecule bone targeting moieties. AB - Bone-targeted drug delivery is an active research area because successful clinical applications of this technology can significantly advance the treatment of bone injuries and disorders. Molecules with bone-targeting potential have been actively investigated as promising moieties in targeted drug delivery systems. In general, bone-targeting molecules are characterized by their high affinity for bone and their predisposition to persist in bone tissue for prolonged periods, while maintaining low systemic concentrations. Proteins, such as monoclonal antibodies, have shown promise as bone-targeting molecules; however, they suffer from several limitations including large molecular size, high production cost, and undesirable immune responses. A viable alternative associated with significantly less side effects is the use of small molecule-based targeting moieties. This review provides a summary of recent findings regarding small molecule compounds with bone-targeting capacity, as well as nanoscale targeted drug delivery approaches employing these molecules. PMID- 27562212 TI - Magnetically-induced elimination of Staphylococcus aureus by magnetotactic bacteria under a swing magnetic field. AB - This study aims to explore a therapeutic tool that kills pathogens by using mechanical force other than temperature. We fabricated a device that generates a swing magnetic field (sMF) with low-heat production and then evaluated the killing effect of magnetotactic bacteria MO-1 on Staphylococcus aureus (S. aureus) under the sMF. S. aureus was only killed under the sMF when attached to MO-1 cells. The killing efficiency increased with increasing attachment ratio of MO-1 cells to S. aureus. Treatment with antibody-coated MO-1 cells under the sMF improved the healing of S. aureus-infected wound. The theoretical analysis demonstrated that MO-1 cells generated a mechanical force of approximately 8kPa under the sMF, thereby exerting on S. aureus and inducing cell death. The proposed platform, which uses magnetotactic bacteria under the sMF to generate mechanical force, provides a basis for development of therapeutic tools to treat infectious diseases. PMID- 27562214 TI - Trends and regional inequalities in mortality from stroke in the context of health care reform in Lithuania. AB - BACKGROUND AND OBJECTIVE: The objective of the study was to analyze mortality from stroke in Lithuania the context of health care reform with particular interest in urban/rural and regional inequalities. Based on the analysis of trends in mortality, and to detection of break-points over two decades of socioeconomic transition, it focused on the challenges in stroke care provision. MATERIALS AND METHODS: The analysis covered the entire country. Information on deaths from 1991 to 2012 was gathered from death certificates held by the Lithuanian Department of Statistics. The joinpoint analysis was used to identify the best-fitting points, wherever a statistically significant change in mortality occurred. Age-standardized mortality rates were calculated for 60 municipalities of Lithuania. RESULTS: The positive break-points in mortality from stroke were registered in 2007 for females and 2008 for males, when the increasing trends reversed to the declining. More positive changes occurred in urban areas, where stroke mortality is lower compare to rural since 1996. Considerable inequalities were disclosed among administrative regions of Lithuania: ratio between the highest and the lowest rates in different municipalities reached 4.88 for males and 3.35 for females. CONCLUSIONS: There are good reasons to expect the favorable stroke mortality trends observed will follow the same direction in the future. Stroke centers are growing up in their competence while networking is also under the development. The new strategies in stroke care should result not only in the declining mortality rates and numbers of severely handicapped stroke patients, but also in diminishing regional and urban/rural inequalities. PMID- 27562213 TI - VARPRISM: incorporating variant prioritization in tests of de novo mutation association. AB - BACKGROUND: Patients with certain genetic diseases, such as autism spectrum disorder, have increased rates of de novo mutations within some protein-coding genes. RESULTS: We introduce the VARiant PRIoritization SuM (VARPRISM), a software package which incorporates functional variant prioritization information to improve the power to detect de novo mutations influencing disease risk. VARPRISM evaluates the consequence of any given exonic mutation on the protein sequence to estimate the likelihood that the mutation is benign or damaging and conducts a likelihood ratio test on the gene level. We analyzed the Simons Simplex Collection of 2508 parent-offspring autism trios using VARPRISM, replicating 44 genes previously implicated in autism susceptibility and identifying 20 additional candidate genes, including MYO1E, KCND3, PDCD1, DLX3, and TSPAN4 (false discovery rate < 0.3). CONCLUSION: By incorporating functional predictions, VARPRISM improved the statistical power to identify de novo mutations increasing disease risks. VARPRISM is available at http://www.hufflab.org/software/VARPRISM . PMID- 27562215 TI - Association between fertilizer-mediated changes in microbial communities and Aedes albopictus growth and survival. AB - Contamination of aquatic habitats with anthropogenic nutrients has been associated with an increase in mosquito larval populations but the underlying mechanisms remain poorly understood. We examined the individual and combined effects of two synthetic fertilizers (ammonium sulfate and potassium chloride) on Aedes albopictus survival, development time, and sex ratio. The bacterial and fungal communities of water samples from different fertilizer treatments were also characterized by MiSeq sequencing of the 16S rRNA gene (bacteria) and internal transcribed spacer 1 (fungi) and their relationship with mosquito survival and development determined. Mosquitoes from ammonium sulfate treatment had significantly lower survival rates and longer development times compared to those from control, potassium chloride or a mixture of the two fertilizers. Fertilizer treatment had no significant effects on Ae. albopictus sex ratio although ammonium sulfate treatment tended to be more biased towards males relative to the other treatments. There were no significant effects of fertilizer treatment on fungal communities. However, potassium chloride treatments had lower bacterial diversity compared to the other treatments and the bacterial community structure of control and potassium chloride treatments differed significantly from that of ammonium sulfate and a mixture of the two fertilizers. Microbial composition but not diversity was significantly associated with mosquito survival and development. These findings suggest that anthropogenic nutrients can have a profound impact on mosquito survival and development. In addition to any potential direct effects on mosquito physiology, our results suggest that fertilizers can act indirectly by disrupting the microbial communities that provide a critical food resource for mosquito larvae. PMID- 27562217 TI - NHS trusts cut overall deficit but remain at "breaking point," leaders warn. PMID- 27562216 TI - Selection of N86F184D1246 haplotype of Pfmrd1 gene by artemether-lumefantrine drug pressure on Plasmodium falciparum populations in Senegal. AB - BACKGROUND: The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia. Monitoring of artemisinin combination therapy (ACT) is critical in order to detect and prevent the spread of resistance in endemic areas. Ex vivo studies and genotyping of molecular markers of resistance can be used as part of this routine monitoring strategy. One gene that has been associated in some ACT partner drug resistance is the Plasmodium falciparum multidrug resistance protein 1 (pfmdr1) gene. The purpose of this study was to assess the drug susceptibility of P. falciparum populations from Thies, Senegal by ex vivo assay and typing molecular markers of resistance to drug components of ACT currently used for treatment. METHODS: The ex vivo susceptibility of 170 P. falciparum isolates to chloroquine, amodiaquine, lumefantrine, artesunate, and artemether was determined using the DAPI ex vivo assay. The high resolution melting technique was used to genotype the pfmdr1 gene at codons 86, 184 and 1246. RESULTS: A significant decrease in IC50 values was observed between 2012 and 2013: from 13.84 to 6.484 for amodiaquine, 173.4 to 113.2 for lumefantrine, and 39.72 to 18.29 for chloroquine, respectively. Increase of the wild haplotype NYD and the decrease of the mutant haplotype NFD (79 and 62.26 %) was also observed. A correlation was observed between the wild type allele Y184 in pfmdr1 and higher IC50 for all drugs, except amodiaquine. CONCLUSION: This study has shown an increase in sensitivity over the span of two transmission seasons, marked by an increase in the WT alleles at pfmdr1. Continuous the monitoring of the ACT used for treatment of uncomplicated malaria will be helpful. PMID- 27562218 TI - Declined Expression of Histone Deacetylase 6 Contributes to Periodontal Ligament Stem Cell Aging. AB - BACKGROUND: Identification of regulators for aging-associated stem cell (SC) dysfunctions is a critical topic in SC biology and SC-based therapies. Periodontal ligament stem cell (PDLSC), a kind of dental mesenchymal SC with dental regeneration potential, ages with functional deterioration in both in vivo and ex vivo expansion. However, little is known about regulators for PDLSC aging. METHODS: Expression changes of a potential regulator for PDLSC aging, histone deacetylase 6 (HDAC6), were evaluated within various models. Senescence associated phenotypic and functional alternations of PDLSC in loss-of-function models for HDAC6 were examined using HDAC6-specific pharmacologic inhibitors or RNA interference-based knockdown. Involvement of p27Kip1 in HDAC6-associated aging was demonstrated by its acetylation and stability changes along with overexpression or functional inhibition of HDAC6. RESULTS: Expression of HDAC6 decreased significantly in replicative senescence and induced SC aging models. Loss-of-function experiments suggested that pharmacologic inhibition of deacetylase activity of HDAC6 accelerated PDLSC senescence and impaired its SC activities, which showed reduced osteogenic differentiation and diminished migration capacities. Examination of markers for proliferative exhaustion of SCs revealed that protein level of p27Kip1 was specifically elevated after HDAC6 inhibition. HDAC6 physically interacted with p27Kip1 and could deacetylate p27Kip1. Importantly, acetylation of p27Kip1 was negatively regulated by HDAC6, which correlated with alteration of p27Kip1 protein levels. CONCLUSION: Data suggest that HDAC6 plays an important role in PDLSC aging, which is dependent, at least partially, on regulation of p27Kip1 acetylation. PMID- 27562219 TI - Comparison Between Dexamethasone and Ibuprofen for Postoperative Pain Prevention and Control After Surgical Implant Placement: A Double-Masked, Parallel-Group, Placebo-Controlled Randomized Clinical Trial. AB - BACKGROUND: Postoperative pain is a potential adverse side effect of oral surgeries, and attempts should be made to prevent or minimize it. This study compares efficacy of preemptive ibuprofen and dexamethasone protocols for pain prevention or control after surgical implant placement. METHODS: This prospective, double-masked, parallel-group, placebo-controlled, randomized clinical trial included 117 patients with planned dental implant placement. Patients were assigned to receive one of three different protocols: 1) 600 mg ibuprofen 1 hour before surgery and another 600 mg 6 hours after the first dose; 2) 4 mg dexamethasone 1 hour before surgery and another 4 mg 6 hours after the first dose; or 3) placebo. Rescue medication (1,000 mg acetaminophen) was made available to each patient, and they were instructed to take it as necessary. Pain intensity was evaluated via a 101-point numeric rating scale and a visual analog scale, and discomfort was evaluated using a four-point verbal rating scale hourly for the first 8 hours after surgery and three times daily for the following 3 days. RESULTS: Ibuprofen and dexamethasone significantly reduced pain (Kruskal Wallis; P <0.05) up to 3 days after surgery and discomfort (P <0.05) up to 2 days after surgery compared with placebo treatment. Both treatments reduced the number of painkillers taken and increased time before the first painkiller was taken (P <0.01). CONCLUSION: Steroidal dexamethasone is as effective as non-steroidal ibuprofen for preventing or controlling postoperative pain and discomfort after surgical implant placement. PMID- 27562220 TI - Influence of Periodontal Disease on Changes of Glycated Hemoglobin Levels in Patients With Type 2 Diabetes Mellitus: A Retrospective Cohort Study. AB - BACKGROUND: Little evidence is available regarding the effects of long-term periodontal infection on diabetes mellitus (DM) control. The aim of this retrospective cohort study is to evaluate influence of periodontal status on changes of glycated hemoglobin (HbA1c) levels of patients with type 2 DM (DMt2). METHODS: Eighty patients (mean age: 56.0 +/- 8.9 years) with DMt2 were included. Patients were non-smokers, aged >=40 years, and using antidiabetic drugs. Demographics, health history, and HbA1c levels were retrieved from medical charts. Probing depth and clinical attachment loss (AL) were recorded. RESULTS: Patients were examined at two time points within a mean interval of 38.6 +/- 6.6 months. Increase in HbA1c over time was statistically significant when severe periodontitis was diagnosed at baseline (2.32%, 95% confidence interval [CI]: 1.50% to 3.15%), in patients showing at least one tooth with >=2 mm of AL progression (2.24%, 95% CI: 1.56% to 2.91%), in males (2.75%, 95% CI: 1.72% to 3.78%), and in those with HbA1c <6.5% at baseline (3.08%, 95% CI: 2.47% to 3.69%). After adjusting for baseline HbA1c, significant changes were still observed for severe periodontitis and progression of AL with increases of 0.85% and 0.9%, respectively. After adjusting for sex and HbA1c, AL progression was also statistically significant, with increases of 0.84%. CONCLUSIONS: Periodontitis progression was associated with increase in HbA1c in patients with DMt2. Identification of these risk factors suggests that periodontal treatment may improve glycemic control of patients with DMt2 by eliminating periodontal infection. PMID- 27562221 TI - Synergistic Approach Using Platelet-Rich Fibrin and 1% Alendronate for Intrabony Defect Treatment in Chronic Periodontitis: A Randomized Clinical Trial. AB - BACKGROUND: Platelet-rich fibrin (PRF) is a reservoir of concentrated platelets that provides a pool of biologic growth-promoting factors and cytokines, which help in mediating regeneration of lost bone and soft tissue maturation. Alendronate (ALN), a member of the amino-bisphosphonate group, is known to enhance periodontal tissue regeneration by inhibiting osteoclast-mediated bone resorption and promoting osteoblast-mediated osteogenesis. The current intervention aims to assess combined effectiveness of PRF and 1% ALN with access therapy in intrabony defect (IBD) treatment in patients with chronic periodontitis (CP). METHODS: Single IBDs in 90 patients were categorized into three groups: 1) group 1 had access therapy alone; 2) group 2 had access therapy with PRF; and 3) group 3 had access therapy with PRF + 1% ALN. Site-specific plaque index, modified sulcus bleeding index, probing depth (PD), clinical attachment level (CAL), and gingival marginal level, included as parameters for clinical assessment, were evaluated before surgery at baseline and 9 months postoperatively. Percentage IBD depth reduction, assessed using radiographs, was evaluated at baseline and postoperatively. RESULTS: Compared with groups 1 and 2, group 3 exhibited significantly greater reduction in PD and gain in CAL postoperatively. Significantly greater IBD depth reduction was shown in group 3 (54.05% +/- 2.88%) compared with group 2 (46% +/- 1.89%) and group 1 (7.33% +/- 4.86%) postoperatively. CONCLUSION: Combined approach therapy of PRF + 1% ALN for IBD treatment in patients with CP showed better clinical parameter outcomes with greater IBD depth reduction compared with PRF and access therapy alone. PMID- 27562223 TI - PCSK9 inhibitors and diabetes risk: a question worth asking? PMID- 27562222 TI - The functional and predictive roles of miR-210 in cryptorchidism. AB - Idiopathic diseases of the reproductive system are important factors leading to male infertility. Many studies have shown that microRNAs (miRNAs) regulate the expression of multiple genes that play a significant role in spermatogenesis and development. We previously showed that microRNA-210 (miR-210) is one of the markedly upregulated microRNAs in the testes of sterile males with maturation arrest (MA). However, the role of miR-210 in spermatogenesis remains unknown. In this study, we found that miR-210 is highly expressed not only in patients with MA but also in patients with cryptorchidism. In addition, miR-210 inhibits the expression of Nuclear Receptor Subfamily 1, Group D, Member 2 (NR1D2) both in vitro and in vivo, particularly in cryptorchidic tissues. To facilitate further research, we established a mouse model of cryptorchidism and were surprised to discover that the miR-210 expression pattern was in accordance with that of patients with cryptorchidism. Thus, we propose that miR-210 may serve as a biomarker of cryptorchidism in clinical tests. PMID- 27562224 TI - Systems-level thinking for nanoparticle-mediated therapeutic delivery to neurological diseases. AB - Neurological diseases account for 13% of the global burden of disease. As a result, treating these diseases costs $750 billion a year. Nanotechnology, which consists of small (~1-100 nm) but highly tailorable platforms, can provide significant opportunities for improving therapeutic delivery to the brain. Nanoparticles can increase drug solubility, overcome the blood-brain and brain penetration barriers, and provide timed release of a drug at a site of interest. Many researchers have successfully used nanotechnology to overcome individual barriers to therapeutic delivery to the brain, yet no platform has translated into a standard of care for any neurological disease. The challenge in translating nanotechnology platforms into clinical use for patients with neurological disease necessitates a new approach to: (1) collect information from the fields associated with understanding and treating brain diseases and (2) apply that information using scalable technologies in a clinically-relevant way. This approach requires systems-level thinking to integrate an understanding of biological barriers to therapeutic intervention in the brain with the engineering of nanoparticle material properties to overcome those barriers. To demonstrate how a systems perspective can tackle the challenge of treating neurological diseases using nanotechnology, this review will first present physiological barriers to drug delivery in the brain and common neurological disease hallmarks that influence these barriers. We will then analyze the design of nanotechnology platforms in preclinical in vivo efficacy studies for treatment of neurological disease, and map concepts for the interaction of nanoparticle physicochemical properties and pathophysiological hallmarks in the brain. WIREs Nanomed Nanobiotechnol 2017, 9:e1422. doi: 10.1002/wnan.1422 For further resources related to this article, please visit the WIREs website. PMID- 27562225 TI - Effect of living with patients on caregiver burden of individual with schizophrenia in China. AB - Caregiver burden may be especially high in China. However, there has been no empirical study comparing burden experienced by caregivers who live with their patient kin and caregivers live separately from their kin. This study compared caregiver burden in cohabiting and non-cohabiting families and examined characteristics that may account for observed differences ion experienced burden. Patients were evaluated on symptoms, insight, attitudes toward medication before discharge and their prime caregivers were evaluated on family burden shortly after admission. Bivariate analysis of covariance and multiple regression analyses were used to compare burden between these two groups and to identify factors that might account for observed differences between them. Of 243 schizophrenic patients, 4.9% lived with their primary caregivers. Caregiver burden was greater among caregivers living with patient kin on three factors, caregiver distress, disrupted routines and assistance provided by caregivers, but not on caregiver perceptions of behavioral problems or suicidality. Multiple regression analysis showed that living with caregiver explained 6.7%, 8.3% and 6.7% of the variance in distress, disrupted routines and helpfulness. Living with a patient was by far the strongest correlate of increased burden experienced by schizophrenia caregivers in this study and these caregivers should be offered community-based support. PMID- 27562226 TI - Determining the effectiveness of the third person interview in the level of insight psychotic patients. AB - The goal of this study was to determine the effectiveness of the third person interview in increasing the level of insight and cooperation in psychotic patients. We used a quasi-experimental posttest design with an alternative method group. A number of 40 individuals with a definite diagnosis of psychosis were selected using a simple random sampling, and were put randomly in an experimental group (third person interview) and an alternative control group (clinical interview). The results indicated that using the third person interview, the insight level of the psychotic patients increased in all dimensions of insight, except awareness of flat or blunted affect and awareness of unsociability. The results of the independent t-test samples showed no significant difference in cooperation between the two groups of psychotic patients. It seems that the ability to consider one's mental viewpoint from other's, is dependent on the relative ability of psychotic patients to represent other's mental states (theory of mind). But, psychotic patients have severe impairment in the ability to represent their own mental states, resulting in an impairment in the recognition of their mental disorder, psychotic symptoms, the need for therapy, and social consequences of their mental disorder. PMID- 27562227 TI - A spiral plasmonic lens with directional excitation of surface plasmons. AB - Conventional plasmonic lenses are composed of curved slits carved through metallic films. Here, we propose a new plasmonic lens based on a metallic slit with an auxiliary groove. When the lens is illumined normally, only inward surface plasmon polaritons (SPPs) can be generated and then focused into a hot spot at the center of the lens. The focusing effect is theoretically investigated by varying the groove parameters and incident polarizations. It is found that this phenomenon exists for both the circular and linear polarizations of incidence. Under optimal groove parameters, the intensity of the focal spot in our lens can be 2.5 times of that in one without grooves for both linearly and circularly polarized illuminations. PMID- 27562228 TI - Is cultural group selection enough? AB - Richerson et al. propose cultural group selection (CGS) as the basis for understanding the evolution of cultural systems. Their proposal does not take into account the nature of cultural idea systems as being constituted at an organizational, rather than an individual level. The sealing partners of the Netsilik Inuit exemplify the problem with their account. PMID- 27562230 TI - Determination of Polycyclic Aromatic Hydrocarbons in Sediment by Pressure Balanced Cold Fiber Solid Phase Microextraction. AB - An improved performance of the cold fiber solid phase microextraction (CF-SPME) technique was accomplished with the use of the pressure-balanced procedure. In order to obtain a pressure-balanced state during extraction at 200 degrees C, 7 mL of air volume was withdrawn from 10 mL commercial vials, while 15 mL was withdrawn from vials where 5 MUL of diethylamine was added as a modifier/displacer. The benefits of the balanced system were demonstrated for determination of polycyclic aromatic hydrocarbons (PAHs) from solid matrixes, including sand and certified sediment samples. Results showed the pressure balanced procedure enhanced the extraction efficiency of the method, especially for high volatility compounds, as the leakage of analytes was mitigated under sample temperature conditions of 200 degrees C. Analytical precision was also improved, with relative standard deviations (RSDs) ranging from 4% to 8% for all analytes under study. For the determination of PAHs in certified sediment samples, pressure-balanced CF-SPME yielded more accurate results in comparison to nonpressure-balanced CF-SPME. The proposed methodology provided the additional benefit of improved recoveries at lower pressures. PMID- 27562229 TI - High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer. AB - BACKGROUND: The progression of colorectal cancer (CRC) involves recurrent amplifications/mutations in the epidermal growth factor receptor (EGFR) and downstream signal transducers of the Ras pathway, KRAS and BRAF. Whether genetic events predicted to result in increased and constitutive signaling indeed lead to enhanced biological activity is often unclear and, due to technical challenges, unexplored. Here, we investigated proliferative signaling in CRC using a highly sensitive method for protein detection. The aim of the study was to determine whether multiple changes in proliferative signaling in CRC could be combined and exploited as a "complex biomarker" for diagnostic purposes. METHODS: We used robotized capillary isoelectric focusing as well as conventional immunoblotting for the comprehensive analysis of epidermal growth factor receptor signaling pathways converging on extracellular regulated kinase 1/2 (ERK1/2), AKT, phospholipase Cgamma1 (PLCgamma1) and c-SRC in normal mucosa compared with CRC stage II and IV. Computational analyses were used to test different activity patterns for the analyzed signal transducers. RESULTS: Signaling pathways implicated in cell proliferation were differently dysregulated in CRC and, unexpectedly, several were downregulated in disease. Thus, levels of activated ERK1 (pERK1), but not pERK2, decreased in stage II and IV while total ERK1/2 expression remained unaffected. In addition, c-SRC expression was lower in CRC compared with normal tissues and phosphorylation on the activating residue Y418 was not detected. In contrast, PLCgamma1 and AKT expression levels were elevated in disease. Immunoblotting of the different signal transducers, run in parallel to capillary isoelectric focusing, showed higher variability and lower sensitivity and resolution. Computational analyses showed that, while individual signaling changes lacked predictive power, using the combination of changes in three signaling components to create a "complex biomarker" allowed with very high accuracy, the correct diagnosis of tissues as either normal or cancerous. CONCLUSIONS: We present techniques that allow rapid and sensitive determination of cancer signaling that can be used to differentiate colorectal cancer from normal tissue. PMID- 27562231 TI - Functional analyses of chitinases in the moss Physcomitrella patens: chitin oligosaccharide-induced gene expression and enzymatic characterization. AB - Plant chitinases play diverse roles including defense against pathogenic fungi. Using reverse-transcription quantitative PCR analysis, we found that six chitinase (PpChi) genes and two genes for chitin elicitor receptor kinases (PpCERKs) are expressed at considerable levels in the moss Physcomitrella patens subsp. patens. The expressed PpChis belonged to glycoside hydrolase family 19 (class I: PpChi-Ia and -Ib; class II: PpChi-IIa and -IIc; and class IV: PpChi-IV) and to glycoside hydrolase family 18 (class V: PpChi-Vb). Treatment with chitin tetramer or hexamer increased the expression of class I and IV PpChi genes and decreased that of class II PpChi genes. Recombinant PpChi-Ia, PpChi-IV, and PpChi Vb were characterized. PpChi-IV exhibited higher activity against chitin tetramer and pentamer than PpChi-Ia did. PpChi-Vb showed transglycosylation activity and PpChi-Ia inhibited fungal growth. These results suggest that chitinases of different classes play different roles in defense mechanism of moss plant against fungal pathogens. PMID- 27562232 TI - Human agricultural economy is, and likely always was, largely based on kinship - Why? AB - We question the sequence of evolutionary transitions leading to ultrasociality in humans proposed by Gowdy & Krall. Evidence indicates that families are, and likely always have been, the primary productive units in human agricultural economies, suggesting that genetic relatedness is key to understanding when the suppression of individual autonomy to the benefit of subsistence groups, that is, extended families, evolved. PMID- 27562233 TI - Prevention of progression to cirrhosis in hepatitis C with fibrosis: effectiveness and cost effectiveness of sequential therapy with new direct-acting anti-virals. AB - BACKGROUND: The new direct-acting anti-virals (DAAs) for hepatitis C virus (HCV) infection offer higher cure rates, but at a much higher cost than the standard interferon-based treatments. AIM: To identify the cost-effective treatment for patients with HCV infection with F3 liver fibrosis who are at high risk of progression to cirrhosis. METHODS: A decision-analytic Markov model compared the health benefits and costs of all currently licensed treatments as single treatments and in sequential therapy of up to three lines. Costs were expressed in pound sterling from the perspective of the UK National Health Service. Health benefits were expressed in quality-adjusted life years. RESULTS: Treatment before progression to cirrhosis always offers the most health benefits for the least costs. Sequential therapy with multiple treatment lines cures over 89% of patients across all HCV genotypes while ensuring a cost-effective use of resources. Cost-effective regimes for HCV genotype 1 patients include first-line oral therapy with sofosbuvir-ledipasvir while peginterferon continues to have a role in other genotypes. CONCLUSIONS: The cost-effective treatment for HCV can be established using decision analytic modelling comparing single and sequential therapies. Sequential therapy with DAAs is effective and cost-effective in HCV patients with F3 fibrosis. This information is of significant benefit to health care providers with budget limitations and provides a sound scientific basis for drug treatment choices. PMID- 27562234 TI - Multisensory integration substantiates distributed and overlapping neural networks. AB - The hypothesis that highly overlapping networks underlie brain functions (neural reuse) is decisively supported by three decades of multisensory research. Multisensory areas process information from more than one sensory modality and therefore represent the best examples of neural reuse. Recent evidence of multisensory processing in primary visual cortices further indicates that neural reuse is a basic feature of the brain. PMID- 27562235 TI - Codon optimization of antigen coding sequences improves the immune potential of DNA vaccines against avian influenza virus H5N1 in mice and chickens. AB - BACKGROUND: Highly pathogenic avian influenza viruses are a serious threat to domestic poultry and can be a source of new human pandemic and annual influenza strains. Vaccination is the main strategy of protection against influenza, thus new generation vaccines, including DNA vaccines, are needed. One promising approach for enhancing the immunogenicity of a DNA vaccine is to maximize its expression in the immunized host. METHODS: The immunogenicity of three variants of a DNA vaccine encoding hemagglutinin (HA) from the avian influenza virus A/swan/Poland/305-135V08/2006 (H5N1) was compared in two animal models, mice (BALB/c) and chickens (broilers and layers). One variant encoded the wild type HA while the other two encoded HA without proteolytic site between HA1 and HA2 subunits and differed in usage of synonymous codons. One of them was enriched for codons preferentially used in chicken genes, while in the other modified variant the third position of codons was occupied in almost 100 % by G or C nucleotides. RESULTS: The variant of the DNA vaccine containing almost 100 % of the GC content in the third position of codons stimulated strongest immune response in two animal models, mice and chickens. These results indicate that such modification can improve not only gene expression but also immunogenicity of DNA vaccine. CONCLUSION: Enhancement of the GC content in the third position of the codon might be a good strategy for development of a variant of a DNA vaccine against influenza that could be highly effective in distant hosts, such as birds and mammals, including humans. PMID- 27562237 TI - Macrophage Activation Syndrome. PMID- 27562236 TI - In Vitro Effects of Lead on Gene Expression in Neural Stem Cells and Associations between Up-regulated Genes and Cognitive Scores in Children. AB - BACKGROUND: Lead (Pb) adversely affects neurodevelopment in children. Neural stem cells (NSCs) play an essential role in shaping the developing brain, yet little is known about how Pb perturbs NSC functions and whether such perturbation contributes to impaired neurodevelopment. OBJECTIVES: We aimed to identify Pb induced transcriptomic changes in NSCs and to link these changes to neurodevelopmental outcomes in children who were exposed to Pb. METHODS: We performed RNA-seq-based transcriptomic profiling in human NSCs treated with 1 MUM Pb. We used qRT-PCR, Western blotting, ELISA, and ChIP (chromatin immunoprecipitation) to characterize Pb-induced gene up-regulation. Through interrogation of a genome-wide association study, we examined the association of gene variants with neurodevelopment outcomes in the ELEMENT birth cohort. RESULTS: We identified 19 genes with significantly altered expression, including many known targets of NRF2-the master transcriptional factor for the oxidative stress response. Pb induced the expression of SPP1 (secreted phosphoprotein 1), which has known neuroprotective effects. We demonstrated that SPP1 is a novel direct NRF2 target gene. Single nucleotide polymorphisms (SNPs) (rs12641001) in the regulatory region of SPP1 exhibited a statistically significant association (p = 0.005) with the Cognitive Development Index (CDI). CONCLUSION: Our findings revealed that Pb induces an NRF2-dependent transcriptional response in neural stem cells and identified SPP1 up-regulation as a potential novel mechanism linking Pb exposure with neural stem cell function and neurodevelopment in children. PMID- 27562238 TI - Reviewing the epigenetics of schizophrenia. AB - BACKGROUND: Epigenetic research in mental health has grown exponentially during the last decade and holds what some claim are "revolutionary" potentials for the development of new interdisciplinary models of mental ill health. Schizophrenia is the most appropriate diagnosis against which to assess progress in this regard. METHOD: Papers on epigenetics and schizophrenia identified in a systematic literature search are subject to a conceptually-driven narrative review that assesses the relations between schizophrenia and epigenetics; considers some issues associated with empirical studies; and thereby identifies key assumptions guiding this research. FINDINGS: The revolutionary potentials of epigenetics are thus far not being realised due to various influences, including a preponderance of hypotheses that begin from a primarily biological question; the "condensation" of environmental influences and their effective reduction to their molecular consequences; and a frequent reliance upon animal studies that effectively preclude some important influences already established as relevant to this diagnosis. CONCLUSION: Epigenetic research in schizophrenia (and mental health generally) could benefit from being more thoroughly interdisciplinary, from testing hypotheses that foreground social as well as biological influences, and from reconsidering its reliance upon psychiatric diagnoses. PMID- 27562239 TI - Thalassospira indica sp. nov., isolated from deep seawater. AB - A taxonomic study using a polyphasic approach was carried out on strain PB8BT, which was isolated from the deep water of the Indian Ocean. Cells of the bacterium were Gram-stain-negative, oxidase- and catalase-positive, curved rods and motile. Growth was observed at salinities of 0-15 % and at temperatures of 10 41 degrees C. The isolate could reduce nitrate to nitrite and degrade Tween 80, but not degrade gelatin. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PB8BT belonged to the genus Thalassospira, with the highest sequence similarity to the closely related type strain Thalassospira tepidiphila 1-1BT (99.7 %), followed by Thalassospira profundimaris WP0211T (99.6 %). Multilocus sequence analysis demonstrated low similarities of 94.1 and 93.7 % between strain PB8BT and the two reference type strains. Digital DNA-DNA hybridization values between strain PB8BT and the two above-mentioned type strains were, respectively, 56.3 and 55.3 %. The principal fatty acids of strain PB8BT were C18 : 1omega6c/C18 : 1omega7c, C19 : 0 cyclo omega8c and C16 : 0. The G+C content of the chromosomal DNA was 54.9 mol%. The quinone was determined to be Q-10 (100 %). Phosphatidylglycerol, phosphatidylethanolamine, and several unidentified phospholipids and lipids were present. Based on phenotypic and genotypic characteristics, strain PB8BT represents a novel species within the genus Thalassospira, for which the name Thalassospira indica sp. nov. is proposed. The type strain of the novel species is PB8BT (=MCCC 1A01103T=LMG 29620T). PMID- 27562240 TI - Gd-Hybridized Plasmonic Au-Nanocomposites Enhanced Tumor-Interior Drug Permeability in Multimodal Imaging-Guided Therapy. AB - An original gadolinium-hybridized plasmonic gold nanocomposite is fabricated to provide an insightful and attractive strategy to overcome both the physiological and pathological barriers of tumor, and increase the transportation and permeability of imaging agents and drugs in tumor interior for achieving high sensitive multimodal imaging and simultaneously improving the therapeutic efficacy of cancer. PMID- 27562242 TI - Cardiorespiratory fitness effect may be under-estimated in 'fat but fit' hypothesis studies. AB - BACKGROUND: Both cardiorespiratory fitness and body fat have been independently related to metabolic syndrome in adolescents; however, the strength of these relationships seems to be dependent on the outcome composition. AIM: To analyse the relationship between cardiorespiratory fitness and body fat combined with different indicators of metabolic risk in adolescents. SUBJECTS AND METHODS: The sample was composed of 957 adolescents (58.7% girls). Cardiorespiratory fitness was obtained using the 20-metre shuttle run test and skinfold thickness was collected for body fat estimation. Metabolic risk score was calculated from waist circumference, systolic and diastolic blood pressure, glucose, HDL cholesterol and triglycerides measurements and an alternative outcome without the central obesity indicator was adopted. Chronological age and somatic maturity were used as covariates. RESULTS: Higher metabolic risk was observed in the highest fat/lowest fit adolescents (p < .05), regardless of sex and outcome. In the regression models, for full metabolic risk score, body fat presented higher coefficients compared to cardiorespiratory fitness in both sexes (boys: 0.501 vs 0.097; girls: 0.485 vs -0.087); however, in the metabolic risk without waist circumference, the coefficients became closer (boys: 0.290 vs -0.146; girls: 0.265 vs -0.120), with a concomitant decrease in body fat and increase in cardiorespiratory fitness coefficients. CONCLUSION: These findings suggest that body fat is strongly related to cardiovascular risk, but, when the outcome is calculated without the central obesity indicator, cardiorespiratory fitness becomes more related to metabolic risk. PMID- 27562241 TI - Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. AB - BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. METHODS: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. RESULTS: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. CONCLUSIONS: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed. PMID- 27562243 TI - Asynchrony index in pressure support ventilation (PSV) versus neurally adjusted ventilator assist (NAVA) during non-invasive ventilation (NIV) for respiratory failure: systematic review and meta-analysis. PMID- 27562244 TI - Ten reasons why ICU patients should be mobilized early. PMID- 27562245 TI - Increased rate of DNR status in hospitalized end-of-life patients in Taiwan. PMID- 27562246 TI - Coherence and multimode correlations from vacuum fluctuations in a microwave superconducting cavity. AB - The existence of vacuum fluctuations is one of the most important predictions of modern quantum field theory. In the vacuum state, fluctuations occurring at different frequencies are uncorrelated. However, if a parameter in the Lagrangian of the field is modulated by an external pump, vacuum fluctuations stimulate spontaneous downconversion processes, creating squeezing between modes symmetric with respect to half of the frequency of the pump. Here we show that by double parametric pumping of a superconducting microwave cavity, it is possible to generate another type of correlation, namely coherence between photons in separate frequency modes. The coherence correlations are tunable by the phases of the pumps and are established by a quantum fluctuation that stimulates the simultaneous creation of two photon pairs. Our analysis indicates that the origin of this vacuum-induced coherence is the absence of which-way information in the frequency space. PMID- 27562247 TI - Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children. AB - BACKGROUND: Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. OBJECTIVE: To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. MATERIALS AND METHODS: We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. RESULTS: We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. CONCLUSION: Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. PMID- 27562248 TI - New insights into negative effects of lithium on sea urchin Paracentrotus lividus embryos. AB - The diffuse use of lithium in a number of industrial processes has produced a significant contamination of groundwater and surface water with it. The increased use of lithium has generated only scarce studies on its concentrations in ambient waters and on its effects on aquatic organisms. Only few contributions have focused on the toxicity of lithium in marine organisms (such as marine animals, algae and vegetables), showing that the toxic effect depends on the animal species. In the present study we describe the morphological and the molecular effects of lithium chloride (LiCl), using the sea urchin Paracentrotus lividus as a model organism. We show that LiCl, if added to the eggs before fertilization, induces malformations in the embryos in a dose-dependent manner. We have also followed by RT qPCR the expression levels of thirty seven genes (belonging to different classes of functional processes, such as stress, development, differentiation, skeletogenesis and detoxifications) to identify the molecular targets of LiCl. This study opens new perspectives for the understanding of the mechanism of action of lithium on marine organisms. The findings may also have relevance outside the world of marine organisms since lithium is widely prescribed for the treatment of human bipolar disorders. PMID- 27562249 TI - AMPK-independent inhibition of human macrophage ER stress response by AICAR. AB - Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear. In a setting of hypoxia-potentiated inflammation induced by SFA palmitate, we found that the AMP-mimetic AMPK activator 5-aminoimidazole-4 carboxamide-1-beta-D-ribofuranoside (AICAR) potently suppressed upregulation of ER stress marker mRNAs and pro-inflammatory cytokines. Furthermore, AICAR inhibited macrophage ER stress responses triggered by ER-stressors thapsigargin or tunicamycin. Surprisingly, AICAR acted independent of AMPK or AICAR conversion to 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl monophosphate (ZMP) while requiring intracellular uptake via the equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) CNT3. AICAR did not affect the initiation of the ER stress response, but inhibited the expression of major ER stress transcriptional effectors. Furthermore, AICAR inhibited autophosphorylation of the ER stress sensor inositol-requiring enzyme 1alpha (IRE1alpha), while activating its endoribonuclease activity in vitro. Our results suggest that AMPK-independent inhibition of ER stress responses contributes to anti-inflammatory and anti-diabetic effects of AICAR. PMID- 27562250 TI - Single Anastomosis Gastric Bypass-Comparative Short-Term Outcome Study of Conversional and Primary Procedures. AB - BACKGROUND: Single anastomosis gastric bypass (SAGB) has been established as a safe and effective bariatric procedure. SAGB has also been suggested as a conversion option from other procedures, but so far not extensively explored in that direction. METHODS: The study retrospectively reviewed and analyzed 154 consecutive SAGB procedures, including 48 conversional SAGB (cSAGB) and 106 primary SAGB (pSAGB). Preoperative physical dimensions and perioperative complications were obtained. Patients were followed 1, 3, and 6 months postoperatively, with weight measurements compared between groups. RESULTS: Operative times were longer in the cSAGB group but length of hospital stay was the same for both groups. Sixty-five percent of the cSAGB group had adjustable banding as a primary operation, and 94 % opted for conversion due to insufficient weight loss or regain thereof. Follow-up data availability was 98, 82, and 79 % for the three checkpoints. Three and 6 months postoperatively, cSAGB had inferior mean excess weight loss (EWL) compared to pSAGB, though both groups were successful after 6 months (mean EWL >50 %). Body mass index loss was significantly higher for pSAGB for the first postoperative 3 months. Low complication rates in both groups precluded statistical comparison in that respect. DISCUSSION: Initial weight loss after conversional SAGB is inferior to primary SAGB after 6 months. The observed safety of cSAGB is comparable to previous evidence for this procedure in the conversional settings. CONCLUSION: SAGB may be considered as a safe and effective conversional procedure, but not as effective as pSAGB for initial weight loss. PMID- 27562251 TI - Size-Dependent Cellular Uptake of DNA Functionalized Gold Nanoparticles. AB - The extensive use of gold nanoparticles (AuNPs) in nanomedicine, especially for intracellular imaging, photothermal therapy, and drug delivery, has necessitated the study of how functionalized AuNPs engage with living biological interfaces like the mammalian cell. Nanoparticle size, shape, surface charge, and surface functionality can affect the accumulation of functionalized AuNPs in cells. Confocal microscopy, flow cytometry, and inductively coupled plasma mass spectrometry demonstrate that CaSki cells, a human cervical cancer cell line, internalize AuNPs functionalized with hairpin, single stranded, and double stranded DNA differently. Surface charge and DNA conformation are shown to have no effect on the cell-nanoparticle interaction. CaSki cells accumulate small DNA AuNPs in greater quantities than large DNA-AuNPs, demonstrating that size is the major contributor to cellular uptake properties. These data suggest that DNA AuNPs can be easily tailored through modulation of size to design functional AuNPs with optimal cellular uptake properties and enhanced performance in nanomedicine applications. PMID- 27562252 TI - Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival. AB - BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. (c) 2016 Wiley Periodicals, Inc. PMID- 27562253 TI - Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes. AB - The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-alpha and gamma receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments. PMID- 27562254 TI - Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. AB - Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies. PMID- 27562255 TI - Cell division licensing in the multi-chromosomal Vibrio cholerae bacterium. AB - Cell division must be coordinated with chromosome replication and segregation to ensure the faithful transmission of genetic information during proliferation. In most bacteria, assembly of the division apparatus, the divisome, starts with the polymerization of a tubulin homologue, FtsZ, into a ring-like structure at mid cell, the Z-ring(1). It typically occurs at half of the cell cycle when most of the replication and segregation cycle of the unique chromosome they generally harbour is achieved(2). The chromosome itself participates in the regulation of cell division, at least in part because it serves as a scaffold to position FtsZ polymerization antagonists(3). However, about 10% of bacteria have more than one chromosome(4), which raises questions about the way they license cell division(3). For instance, the genome of Vibrio cholerae, the agent of cholera, is divided between a 3 Mbp replicon that originates from the chromosome of its mono-chromosomal ancestor, Chr1, and a 1 Mbp plasmid-derived replicon, Chr2 (ref. 5). Here, we show that Chr2 harbours binding motifs for an inhibitor of Z-ring formation, which helps accurately position the V. cholerae divisome at mid-cell and postpones its assembly to the very end of the cell cycle. PMID- 27562256 TI - Caulobacter crescentus intrinsic dimorphism provides a prompt bimodal response to copper stress. AB - Stress response to fluctuating environments often implies a time-consuming reprogramming of gene expression. In bacteria, the so-called bet hedging strategy, which promotes phenotypic stochasticity within a cell population, is the only fast stress response described so far(1). Here, we show that Caulobacter crescentus asymmetrical cell division allows an immediate bimodal response to a toxic metals-rich environment by allocating specific defence strategies to morphologically and functionally distinct siblings. In this context, a motile swarmer cell favours negative chemotaxis to flee from a copper source, whereas a sessile stalked sibling engages a ready-to-use PcoAB copper homeostasis system, providing evidence of a prompt stress response through intrinsic bacterial dimorphism. PMID- 27562257 TI - High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice. AB - Immunoglobulin A (IgA) is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defence against pathogens and in the maintenance of intestinal homeostasis. However, how secreted IgA regulates gut microbiota is not completely understood. In this study, we isolated monoclonal IgA antibodies from the small intestine of healthy mouse. As a candidate for an efficient gut microbiota modulator, we selected a W27 IgA, which binds to multiple bacteria, but not beneficial ones such as Lactobacillus casei. W27 could suppress the cell growth of Escherichia coli but not L. casei in vitro, indicating an ability to improve the intestinal environment. Indeed W27 oral treatment could modulate gut microbiota composition and have a therapeutic effect on both lymphoproliferative disease and colitis models in mice. Thus, W27 IgA oral treatment is a potential remedy for inflammatory bowel disease, acting through restoration of host-microbial symbiosis. PMID- 27562258 TI - Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare. AB - Whole metagenome analysis has the potential to reveal functional triggers of skin diseases, but issues of cost, robustness and sampling efficacy have limited its application. Here, we have established an alternative, clinically practical and robust metagenomic analysis protocol and applied it to 80 skin microbiome samples epidemiologically stratified for atopic dermatitis (AD). We have identified distinct non-flare, baseline skin microbiome signatures enriched for Streptococcus and Gemella but depleted for Dermacoccus in AD-prone versus normal healthy skin. Bacterial challenge assays using keratinocytes and monocyte-derived dendritic cells established distinct IL-1-mediated, innate and Th1-mediated adaptive immune responses with Staphylococcus aureus and Staphylococcus epidermidis. Bacterial differences were complemented by perturbations in the eukaryotic community and functional shifts in the microbiome-wide gene repertoire, which could exacerbate a dry and alkaline phenotype primed for pathogen growth and inflammation in AD-susceptible skin. These findings provide insights into how the skin microbial community, skin surface microenvironment and immune system cross-modulate each other, escalating the destructive feedback cycle between them that leads to AD flare. PMID- 27562259 TI - The physiology and habitat of the last universal common ancestor. AB - The concept of a last universal common ancestor of all cells (LUCA, or the progenote) is central to the study of early evolution and life's origin, yet information about how and where LUCA lived is lacking. We investigated all clusters and phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes in order to reconstruct the microbial ecology of LUCA. Among 286,514 protein clusters, we identified 355 protein families (~0.1%) that trace to LUCA by phylogenetic criteria. Because these proteins are not universally distributed, they can shed light on LUCA's physiology. Their functions, properties and prosthetic groups depict LUCA as anaerobic, CO2-fixing, H2-dependent with a Wood-Ljungdahl pathway, N2-fixing and thermophilic. LUCA's biochemistry was replete with FeS clusters and radical reaction mechanisms. Its cofactors reveal dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosyl methionine dependent methylations. The 355 phylogenies identify clostridia and methanogens, whose modern lifestyles resemble that of LUCA, as basal among their respective domains. LUCA inhabited a geochemically active environment rich in H2, CO2 and iron. The data support the theory of an autotrophic origin of life involving the Wood-Ljungdahl pathway in a hydrothermal setting. PMID- 27562260 TI - Model-based projections of Zika virus infections in childbearing women in the Americas. AB - Zika virus is a mosquito-borne pathogen that is rapidly spreading across the Americas. Due to associations between Zika virus infection and a range of fetal maladies(1,2), the epidemic trajectory of this viral infection poses a significant concern for the nearly 15 million children born in the Americas each year. Ascertaining the portion of this population that is truly at risk is an important priority. One recent estimate(3) suggested that 5.42 million childbearing women live in areas of the Americas that are suitable for Zika occurrence. To improve on that estimate, which did not take into account the protective effects of herd immunity, we developed a new approach that combines classic results from epidemiological theory with seroprevalence data and highly spatially resolved data about drivers of transmission to make location-specific projections of epidemic attack rates. Our results suggest that 1.65 (1.45-2.06) million childbearing women and 93.4 (81.6-117.1) million people in total could become infected before the first wave of the epidemic concludes. Based on current estimates of rates of adverse fetal outcomes among infected women(2,4,5), these results suggest that tens of thousands of pregnancies could be negatively impacted by the first wave of the epidemic. These projections constitute a revised upper limit of populations at risk in the current Zika epidemic, and our approach offers a new way to make rapid assessments of the threat posed by emerging infectious diseases more generally. PMID- 27562261 TI - Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. AB - The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene. PMID- 27562262 TI - Surveys, simulation and single-cell assays relate function and phylogeny in a lake ecosystem. AB - Much remains unknown about what drives microbial community structure and diversity. Highly structured environments might offer clues. For example, it may be possible to identify metabolically similar species as groups of organisms that correlate spatially with the geochemical processes they carry out. Here, we use a 16S ribosomal RNA gene survey in a lake that has chemical gradients across its depth to identify groups of spatially correlated but phylogenetically diverse organisms. Some groups had distributions across depth that aligned with the distributions of metabolic processes predicted by a biogeochemical model, suggesting that these groups performed biogeochemical functions. A single-cell genetic assay showed, however, that the groups associated with one biogeochemical process, sulfate reduction, contained only a few organisms that have the genes required to reduce sulfate. These results raise the possibility that some of these spatially correlated groups are consortia of phylogenetically diverse and metabolically different microbes that cooperate to carry out geochemical functions. PMID- 27562264 TI - Microbiome: Ecology of eczema. PMID- 27562263 TI - Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47. AB - Suppression of major histocompatibility complex (MHC) class II antigen presentation is believed to be among the major mechanisms used by Mycobacterium tuberculosis to escape protective host immune responses. Through a genome-wide screen for the genetic loci of M. tuberculosis that inhibit MHC class II restricted antigen presentation by mycobacteria-infected dendritic cells, we identified the PE_PGRS47 protein as one of the responsible factors. Targeted disruption of the PE_PGRS47 (Rv2741) gene led to attenuated growth of M. tuberculosis in vitro and in vivo, and a PE_PGRS47 mutant showed enhanced MHC class II-restricted antigen presentation during in vivo infection of mice. Analysis of the effects of deletion or over-expression of PE_PGRS47 implicated this protein in the inhibition of autophagy in infected host phagocytes. Our findings identify PE_PGRS47 as a functionally relevant, non-redundant bacterial factor in the modulation of innate and adaptive immunity by M. tuberculosis, suggesting strategies for improving antigen presentation and the generation of protective immunity during vaccination or infection. PMID- 27562266 TI - A cure for germophobia. PMID- 27562265 TI - Digging the dirt. PMID- 27562267 TI - Evolution: A four billion year old metabolism. PMID- 27562268 TI - Quantifying human impact on Earth's microbiome. PMID- 27562269 TI - Epidemiology: Making high-res Zika maps. PMID- 27562271 TI - Transparency in our decision making. PMID- 27562270 TI - Microbial ecology: Seeing growth without culture. PMID- 27562272 TI - Improved Outcomes Following a Single Session Web-Based Intervention for Problem Gambling. AB - Research suggests online interventions can have instant impact, however this is yet to be tested with help-seeking adults and in particular those with problem gambling. This study seeks to determine the immediate impact of a single session web-based intervention for problem gambling, and to examine whether sessions evaluated positively by clients are associated with greater improvement. The current study involved 229 participants classified as problem gamblers who agreed to participate after accessing Gambling Help Online between November 2010 and February 2012. Almost half were aged under 35 years of age (45 %), male (57 %) as well as first time treatment seekers (62 %). Participants completed measures of readiness to change and distress both prior to and post-counselling. Following the provision of a single-session of counselling, participants completed ratings of the character of the session (i.e., degree of depth and smoothness) post counselling. A significant increase in confidence to resist and urge to gamble and a significant decrease in distress (moderate effect size; d = .56 and .63 respectively) was observed after receiving online counselling. A hierarchical regression indicated the character of the session was a significant predictor of change in confidence, however only the sub-scale smoothness was a significant predictor of change in distress. This was the case even after controlling for pre session distress, session word count and client characteristics (gender, age, preferred gambling activity, preferred mode of gambling, gambling severity, and preferred mode of help-seeking). These findings suggest that single session web based counselling for problem gambling can have immediate benefits, although further research is required to examine the impact on longer-term outcomes. PMID- 27562273 TI - Individual-based approach to epidemic processes on arbitrary dynamic contact networks. AB - The dynamics of contact networks and epidemics of infectious diseases often occur on comparable time scales. Ignoring one of these time scales may provide an incomplete understanding of the population dynamics of the infection process. We develop an individual-based approximation for the susceptible-infected-recovered epidemic model applicable to arbitrary dynamic networks. Our framework provides, at the individual-level, the probability flow over time associated with the infection dynamics. This computationally efficient framework discards the correlation between the states of different nodes, yet provides accurate results in approximating direct numerical simulations. It naturally captures the temporal heterogeneities and correlations of contact sequences, fundamental ingredients regulating the timing and size of an epidemic outbreak, and the number of secondary infections. The high accuracy of our approximation further allows us to detect the index individual of an epidemic outbreak in real-life network data. PMID- 27562274 TI - [Excessive medical problems in the treatment of common eye diseases in children]. AB - In this paper, some typical excessive medical problems in the treatment of common eye diseases in children were listed as follows: unnecessary examinations carried out for children with little or no corresponding complaints; prescription for spectacles for physiological hyperopia or astigmatism in children; over diagnosis, over-or nonstandard-treatment for amblyopia; strabismus surgeries performed in children with esotropia but without full optical correction of hyperopic refractive error, in children with monocular strabismus and amblyopia but without standard cover therapy, in children with intermittent exotropia but without optical correction of myopic refractive errors and myopic anisometropia, and without evaluation of their fusional control ability; exaggerated the harm of myopia and the curative effect of Orthokeratology contact lenses without considering the patient's compliance; cataract surgery performed in infants with partial opacity of the lens that has little effect on the vision. Every ophthalmologist should work based on evidence-based preferred practice pattern, professional standards and expert consensus to promote the standardization of the diagnosis and treatment of children's common eye diseases in China. (Chin J Ophthalmol, 2016, 52: 561-564). PMID- 27562275 TI - [When and how to perform the superior oblique tucking surgery]. AB - Either superior oblique weakening or strengthening surgery is the most complicated and most difficult to perform in the field of strabismus surgery. The effect of superior oblique surgery is also unpredictable. In addition, improper superior oblique strengthening surgery may produce limited elevation in adduction (iatrogenic Brown syndrome). In this article, we reviewed the history of superior oblique surgery, especially on when and how to perform the superior oblique strengthening surgery for providing reference to the clinicians in the field of strabismus and pediatric ophthalmology. (Chin J Ophthalmol, 2016, 52: 565-567). PMID- 27562276 TI - [The application of anterior segment optical coherence tomography in residual strabismus surgery]. AB - OBJECTIVE: To evaluate the application of anterior segment optical coherence tomography (ASOCT) in surgical design for residual horizontal strabismus patients. METHODS: This article was a retrospective case series analysis. Total 20 residual strabismus patients (13 with residual exotropia and 7 with residual esotropia) in Eye Hospital of Wenzhou Medical University from Jan 2009 to Jan 2011 were studied. Routine strabismus examinations were completed preoperatively. The distance between insertion of horizontal rectus muscles and corneal limbus were measured with ASOCT preoperatively and calipers intraoperatively. Reoperational amount and method for residual strabismus patients were designed according to the limbus-insertion distance. The paired t test was used to compare the agreement between two methods of measurement of limbus-insertion distance. The cure rates of reoperation were analyzed. RESULTS: No statistical significance was observed between the measurements with ASOCT (7.7+/-1.7) mm and calipers (7.8+/-1.1)mm (t=-1.37, P=0.19). According to ASOCT image, the second surgical method was re-recession muscle for 4 patients; re-recession of original performed muscle combined with antagonist muscle resection for 10 patients and antagonist muscle resection combined with horizontal rectus muscle recession in fellow eye for 6 patients. All the surgical processes went on successfully, no severe intraoperative and postopereative complications were noted. Sixteen cases were cured (80%) . CONCLUSIONS: Horizontal rectus muscle evaluation with ASOCT preoperatively may benefit the choice of performed muscle, calculation of surgical amount, reduction of unnecessary surgical procedure and optimization second surgical design for residual strabismus patients. (Chin J Ophthalmol, 2016, 52: 568-573). PMID- 27562277 TI - [Clinical characteristics and surgical treatment of idiopathic congenital nystagmus in 224 patients]. AB - OBJECTIVE: To study clinical characteristics and surgical treatment of idiopathic congenital nystagmus (ICN). METHODS: A retrospective study was conducted in 224 patients with ICN in Tianjin eye hospital from July 2007 to February 2013. RESULTS: There were 224 patients, 158 (70.54%) males and 66 (29.5%) females, mean age was (11.6+/-8.4) years and (11.4+/-6.4) years separately. Horizontal nystgamus happened in 215 cases, 3 cases were vertical type and 6 cases were mixed. 214 cases were with no history of operation and 10 patients had ever underwent surgeries before. Furthermore, 151 patients combined with strabismus and refractive error, anterior segment or retinal disorders, which accounting for 67.4% of all the patients. 48 patients were associated myopia, 30 patients with hyperopia, 43 patients with strabismus. Among them, 153 cases of compensatory head position direction were horizontal with face turn, 43 cases (43/153, 28.1%) showed face turning to the left, 110 cases (110/153, 71.9%) showed face turning to the right. Surgeries were designed according to the compensatory head position and head retroversion angle. For 15 patients with double intermediate zones, the position which was often used with good visual function was chosen for operation design. As for the patients with nystagmus and strabismus, the transfer null zone to primary position for the dominant eye and strabismus surgery for the other eye was chosen. And for complicated patients with compensative head position, the dominant head posture were designed for surgery. CONCLUSIONS: ICN is dominated by male with variable clinical manifestations. Surgical choice for ICN depends on the direction of head position and if there is strabismus accompanying it.The aim of ocular muscle surgery is to transfer null zone to primary position. (Chin J Ophthalmol, 2016, 52: 574-578). PMID- 27562278 TI - [Clinical observation of the graduated "hang-back" recession of superior oblique in a-pattern strabismus with superior oblique overaction]. AB - OBJECTIVE: To investigate the effect and safety of the graduated "hang-back" recession of superior oblique (SO) in treatment of A-pattern strabismus with superior oblique overaction (SOOA). METHODS: Retrospective study. The clinical data of 15 cases (28 eyes), who underwent graduated "hang-back" recession of SO depending on the scales of SOOA, were collected and analyzed. The principle we carried on was hang-back recession 8-10mm for SOOA+4, 6 to 8 mm for SOOA+3, 5 to 6 mm for SOOA+2 and 4 mm for SOOA+1. The pre-operative and post-operative outcomes, including the ocular alignment, ocular motility, A-pattern and objective torsion demonstrated by fundus photographs were evaluated and compared. RESULTS: In 15 cases (28 eyes), 2 cases had unilateral hang-back recession of SO for unilateral SOOA. Thirteen cases had bilaterally symmetric or asymmetric hang back procedure. All the patients had no A pattern after surgery. The average difference of pre- and post-operative A-patterns were (24.5+/-11.9) PD and (3.2+/ 4.2) PD in 13 cases with bilateral SOOA (t=8.01, P=0.00). The bilateral SO hang back procedure could correct A-pattern in an amount of 21.3+/-10.3 PD in average. The average amount of pre- and post-operative SOOA were +3.0+/-2.0 and +0.5+/-1.0 in 28 eyes (Z=-4.70, P=0.00). Only 1 case remained residual SOOA+2.0. Fundus photos were measured by SigmascanPro5.0 program and the average pre- and post operative torsion were +5.4 degrees +/-3.9 degrees and +0.3 degrees +/-5.6 degrees (The baseline was the line across the center of optic disc. The torsional angle was measured between the line across the fovea and and the line across the center of optic.) in 28 eyes (t=5.76, P=0.00). The average corrected torsion was 5.2 degrees +/-4.8 degrees . The pre-operative SOOA was related with the pre-operative torsion (Spearman correlation coefficient=0.47, P=0.01). The surgical amounts in 28 eyes were various from 4 to 10 mm (8+/-12 mm in average), which were not related with the corrected torsion (Spearman correlation coefficient=0.17, P=0.39), but related with pre-operative torsion (Spearman correlation coefficient=0.44, P=0.02). The total amounts on both eyes in patients operated by bilateral SO hang-back procedure were also not related with the corrected A-pattern (Spearman correlation coefficient=0.55, P=0.05). No case had secondary SO palsy and V-pattern after surgery. CONCLUSIONS: The graduated "hang back" recession of SO is optional for treatment of mild to moderate SOOA and A pattern. It corrected objectively in-torsion without risks of secondary SO palsy and V-pattern. It is a safe and effective SO weakening procedure. (Chin J Ophthalmol, 2016, 52: 579-583). PMID- 27562279 TI - [Application of disparity discriminating accuracy test in evaluating the stereopsis of postoperative intermittent exotropia]. AB - OBJECTIVE: To discuss the application of disparity discriminating accuracy test in evaluating the stereopsis of postoperative intermittent exotropia. METHODS: Patients with intermittent exotropia who underwent surgery during July 2011 to June 2013 were followed up. The stereoacuity was examined by Titmus Stereotest, Randot Stereotest and Frisby Stereotest. Twenty adult cases whose stereoacuity reached normal were chosen as experimental group. Twenty healthy adults were selected as normal control group. Both groups were examined with disparity discriminating accuracy test. Discriminating accuracy of the two groups were analyzed with Two-Way ANOVA method. Test-retest reliability was analyzed with Intraclass Correlation Coefficient analysis. RESULTS: The test-retest reliability of disparity discriminating accuracy test is excellent (ICC=0.99, P<0.01) . Discriminating accuracy under different disparities in experimental group were 0.56+/-0.09, 0.67+/-0.14, 0.77+/-0.15, 0.82+/-0.14, 0.85+/-0.11, 0.85+/-0.14, 0.87+/-0.10, 0.84+/-0.16, while those in control group were 0.77+/-0.09, 0.88+/ 0.09, 0.93+/-0.08, 0.91+/-0.09, 0.95+/-0.08, 0.96+/-0.05, 0.97+/-0.06, 0.96+/ 0.04. There were statistically significant differences between them (F=38.06, P<0.01) . The discriminating ability of group grating in both groups was affected by the size of disparity. Under situation of small disparity, a large difference was found between the experimental group (0.67+/-0.12)and control group(0.86+/ 0.07) (F=4.84, P<0.05). CONCLUSIONS: Stereoscopic function can be evaluated comprehensively with disparity discriminating accuracy test. Use this test, a certain degree of dysfunction in stereopsis can still be found in postoperative intermittent exotropic patients who reached normal stereoacuity examined with traditional stereotests. (Chin J Ophthalmol, 2016, 52: 584-588). PMID- 27562280 TI - [The effect of superior oblique tucking on the Bielschowsky head tilt test]. AB - OBJECTIVE: To investigate the effect of superior oblique tucking on the Bielschowsky head tilt test. METHODS: A retrospective analysis of 22 patients with congenital unilateral superior oblique palsy, who underwent tucking of the superior oblique tendon in Tianjin Eye Hospital, depending on vertical deviation in the primary position, ocular motility, objective cyclotorsion and abnormal head posture. Bielschowsky head tilt test was evaluated quantitatively by the prism cover test. Alpha positive Bielschowsky head tilt test was defined as one in which the vertical deviation when the head tilt to the side of the paresis was at least 5. 0(?) greater than that on tilt to the uninvolved side. The follow-up period ranged from 3 to 12 months (mean 4.6 months). Kolmogorov-Smirnov (K-S), Rank sum test and Spearman correlation analysis statistical methods were used in this study. RESULTS: All patients had vertical deviation and significant abnormal head posture before operation. After the procedure of superior oblique tucking,vertical deviation and symptom of unacceptable abnormal head posture were ameliorated or disappeared. OBJECTIVE torsion was 15.62 degrees +/-7.36 degrees before the surgery, 9.91 degrees +/-10.09 degrees 1d after the surgery and 11.25 degrees +/-9.17 degrees at the last follow-up visit, respectively (P<0.05). We found that there were positive correlations between the objective cyclotorsion and the vertical deviation difference value between the paralyzed side and uninvolved side at 1 d after the surgery and last follow-up visit(P<0.05). The vertical deviation of the paresised eye when the head tilted to the side of paresis side and uninvolved side difference were 5.00(?)-17.00(?), average 8.68(?)+/-3.23(?), 1.00(?)-8.00(?),average 3.36(?)+/-2.01(?) and 0.00(?) 14.00(?),average 3.77(?)+/-3.01(?), preoperatively, 1d after the surgery and at the last follow-up visit respectively. Using Rank sum test, the pre-and postoperative difference was statistically significant (Z=-4.64, P<0.01). A positive Bielschowsky head tilt test was found in all cases preoperatively. The results of Bielschowsky tilt test was still positive in 5 cases and negative in 17 cases (77.3%). CONCLUSIONS: In most cases with unilateral superior oblique paresis, the results of Bielschowsky tilt test became negative after superior oblique tucking. The long-standing results is worthy of observation. (Chin J Ophthalmol, 2016, 52: 589-595). PMID- 27562281 TI - [Utilization of Quality-of-life assessment Questionnaires for Intermittent Exotropia in China]. AB - OBJECTIVE: To evaluate the reliability and validity of Chinese version of Quality of-life assessment Questionnaires for Intermittent Exotropia (CIXTQ). METHODS: Cross-sectional study. The original English version of the IXTQ was translated into Chinese. The final Chinese version of the IXTQ (CIXTQ) consists of 3 parts: the 12-item child CIXTQ (for children >=5 and<8 years old and >=8 and<18 years old, respectively, to assess their health quality of life (HRQoL)), the 12-item proxy CIXTQ (for parents to assess children's HRQoL), and the 17-item parent CIXTQ (containing functional, psychosocial, and surgery subscales; for parents to assess their HRQoL). 175 IXT children and 151 control children along with one of their parents were recruited to answer the CIXTQ. Cronbach's alpha coefficient and split-half reliability were used to test the internal consistency reliability of the CIXTQ. Kappa coefficient was used to assess the test-retest reliability. Scale-level content validity index/average (S-CVI/Ave) was used to evaluate the content validity of the CIXTQ. Principal component analysis (PCA) was used to verify the construct validity of the parent CIXTQ. Comparison of different CIXTQ scores in IXT patients with controls was conducted by independent-samples t test to evaluate the discriminate validity of the CIXTQ. RESULTS: For all scales and subscales of the CIXTQ in different age groups, the Cronbach's alpha ranged from 0.804 to 0.963; the split-half reliability ranged from 0.658 to 0.963 and was higher than 0.7 except for the proxy CIXTQ for children aged >=5 and<8 years old; the test-retest reliability ranged from 0.569 to 0.944. The S-CVI/Ave of the child, proxy and parent CIXTQ was 0.988, 0.988 and 0.966, respectively. Principal factors identified by PCA for the parent CIXTQ could be regrouped into the originally described 3 subscales which was functional, social psychology and surgery in different age groups. The mean scores of all the scales and subscales among IXT children and their parents (8.0+/-12.5-81.6 +/-15.1) were significantly lower than these among control children and their parents (83.1+/-11.3-99.6+/ 1.2) (t values range from -50.36 to -6.93, P<0.001). CONCLUSIONS: The CIXTQ are useful tools to evaluate the influence of IXT on HRQoL among Chinese children and their parents. (Chin J Ophthalmol, 2016, 52: 596-603). PMID- 27562282 TI - [The effect of long-term contact lens wear on the morphology of meibomian glands]. AB - OBJECTIVE: To evaluate the effect of long-term contact lens (CL) wear on the morphology of meibomian glands (MGs) using meiboscore and digital analysis. METHODS: Retrospective study. Sixty right eyes of sixty patients were involved in this study, and the data were analyzed retrospectively. According to the duration of CL wear, all patients were divided into three groups, nonwear group (n=21), short-term group (duration of CL wear <=3 years, n=19) and long-term group (duration of CL wear>3 years, n=20). Digital images of MGs obtained by meibography were analyzed using Image J software, providing the area percentage of MGs loss. The meiboscores were also examined, and the data were analyzed using one-way ANOVA and Kruskal-Wallis test. RESULTS: Ten out of 21 nonwearers were scored 0 point, and 11 were scored 1 point in the upper lid meiboscores, while 7 were scored 0 point, 9 were scored 1 point, and 5 were scored 2 points in the total meiboscores. Seven out of 19 short-term wearers were scored 0 point, 10 were scored 1 point, and 2 were scored 2 points in the upper lid meiboscores, while 5 were scored 0 point, 6 were scored 1 point, 6 were scored 2 points, and 2 were scored 3 points in the total meiboscores. Four out of 20 long-term wearers were scored 0 point, 7 were scored 1 point, and 9 were scored 2 points in the upper lid meiboscores, while 3 were scored 0 point, 4 were scored 1 point, 4 were scored 2 points, 4 were scored 3 points, 4 were scored 4 points, and 1 was scored 5 points in the total meiboscores. The meiboscores of the upper eyelid and total meiboscores among the three groups were significantly different (Hc=9.967, P=0.007; Hc=9.725, P=0.008). The meiboscores of the upper eyelid and total meiboscores were significantly higher in the long-term group compared to the nonwear group (Z=102.500, P=0.003, Z=100.500, P=0.003) and the short-term group (Z=120.500, P=0.050, Z=117.500, P=0.041). No significant difference was found between the short-term group and the nonwear group. The median of the MGs loss area percentage in the upper eyelid of the nonwear, short-term and long-term groups was 9.2%, 13.3% and 16.7%, respectively. The median of the total MGs loss area percentage in the nonwear, short-term and long-term groups were 6.6%, 8.8% and 13.0%, respectively. The above medians were significantly different among the three groups (Hc=6.390, P=0.041; Hc=7.019, P=0.030). They were significantly larger in the long-term wearers than the nonwearers (Z=120.500, P=0.019, Z=120.500, P=0.009). No significant difference was found between the short-term group and the nonwear group, or between the short-term group and the long-term group. No significant differences in the meiboscores or MGs loss area percentage in the lower eyelid were noticed among the three groups. The area under the curve of total area percentage of MGs loss in receiver operating characteristic analysis was 0.981 (P<0.001). CONCLUSIONS: Long-term (more than 3 years) CL wear can cause MGs loss. Digital analysis is helpful in the morphologic evaluation of MGs. (Chin J Ophthalmol, 2016, 52: 604-609). PMID- 27562283 TI - [Craniosynostosis and strabismus]. AB - Craniosynostosis(CS), the premature fusion of cranial sutures leading to an abnormal shape and precocious maturity of skull, is classified into Non-syndromic Craniosynostosis (NSC) and Syndromic Craniosynostoses(SC).NCS only has different abnormality of skull according to which cranial suture is involved while extra malformation of midface and limbs present in SCS. Common SCS contains Crouzon Syndrome, Apert Syndrome, Pfeiffer Sydrome, and etc. The clinical manifestation of CS includes malformation of skull, intracranial hypertension, brain hernia, developmental disorder of cerebral function, strabismus, and etc, while SCS has more complex manifestation. Along with the improvement of multidisciplinary cooperation, the ophthalmic complication of CS, like strabismus, is recognised by oculists gradually. This review is summarizing the clinical manifestation, complicated strabismus, pathogenesis and multidisciplinary cure of CS. (Chin J Ophthalmol, 2016, 52: 626-630). PMID- 27562284 TI - [Recent studies on corneal epithelial barrier function]. AB - Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635). PMID- 27562285 TI - [Behcet's disease and infection]. AB - Behcet's disease (BD) is a systemic vasculitis of unknown etiology. Uveitis, which is common and therapeutically challenging, is the major ocular manifestation of BD. Researches have shown that, in addition to the genetic components (e.g. HLA-B51), environmental factors such as infection also play important roles in the pathogenesis of BD. In recent years, with the advances in bio-detecting technologies, accumulating evidence has shown an association between microbial infections and previously believed non-infectious immune disorders. Specifically, there has been increasing research interest in roles of infection in pathogenesis of BD. A variety of microbes, including streptococcus sanguis, staphylococcus aureus, intestinal flora, herpes simplex virus and etc., have been suggested to be involved. The objective of this article is to review current research progress concerning BD and infection, as well as to provide some recommendations for future investigations into this subject. (Chin J Ophthalmol, 2016, 52: 636-640). PMID- 27562286 TI - Can a seed-sized tool from Texas spare clinically node positive breast cancer patients from a complete axillary dissection? PMID- 27562287 TI - Ophiostomatoid fungi associated with mangroves in South Africa, including Ophiostoma palustre sp. nov. AB - Mangrove trees are continuously under stress due to environmental and/or anthropogenic pressures, which expose them to attack by pathogens, compromising their survival. Ophiostomatoid fungi cause sap stain and diseases of a wide spectrum of tree species globally. These fungi infect trees through natural, insect, animal and/or human made wounds. During routine surveys of mangrove trees in South Africa, wounds on branches and stems of Avicennia marina were regularly monitored for the presence of ophiostomatoid fungi at ten study sites in the country. The stems of four mangrove species, A. marina, Bruguiera gymnorrhiza, Rhizophora mucronata and Barringtonia racemosa were also wounded and evaluated for the appearance of these fungi. Ophiostomatoid fungi were obtained from the mangrove associate B. racemosa, but not from any of the true mangroves. Analyses of DNA sequence data for the internal transcribed spacer, beta-tubulin, calmodulin and translation elongation factor gene regions revealed that the fungi isolated from the wounds on B. racemosa belong to three species in the Ophiostomataceae, including a new taxon described here as Ophiostoma palustre sp. nov. These results suggest that the mangrove associate B. racemosa is more prone to colonization by ophiostomatoid fungi than the true mangroves. PMID- 27562288 TI - Two liquid chromatographic approaches for the simultaneous determination of xipamide and its degradation product (2,6-xylidine) using time-programmed fluorescence detection. AB - A study of the performance of reversed-phase chromatography with a programmable multiwavelength fluorimetric technique using either conventional hydro-organic or micellar eluent is established for the determination of xipamide (XIP) in the presence of its degradation product, 2,6-xylidine (XY). In conventional liquid chromatography (CLC), the analyses were carried out on a Promosil ODS 100 A column (250 mm * 4.6 mm i.d., 5 MUm) using a mobile phase consisting of methanol/0.1 M phosphate buffer (65: 35, v/v) at pH 4.0. For micellar liquid chromatography (MLC), a short Spherisorb column (150 mm * 4.6 mm i.d., 5 MUm) was employed in conjunction with a greener mobile phase (pH 5.0) containing 0.1 M sodium dodecyl sulfate and 15% n-propanol. CLC proved to be superior to MLC in terms of sensitivity for the determination of the degradation product because it could detect trace amounts down to 10.0 ng/ml of XY as a degradation product in XIP. However, MLC represents an eco-friendly approach for the simultaneous determination of XIP and XY. In addition, the opportunity for the direct introduction of biological matrices into the chromatographic system is one of the distinctive benefits of MLC. The proposed methods were applied for the determination of XIP in its tablets, human urine and content uniformity testing. The results of the proposed methods were statistically compared with those obtained using the comparison fluorimetric method, revealing no significant differences in the performance of the methods regarding accuracy and precision. PMID- 27562289 TI - Ovarian ageing: the role of mitochondria in oocytes and follicles. AB - BACKGROUND: There is a great inter-individual variability of ovarian ageing, and almost 20% of patients consulting for infertility show signs of premature ovarian ageing. This feature, taken together with delayed childbearing in modern society, leads to the emergence of age-related ovarian dysfunction concomitantly with the desire for pregnancy. Assisted reproductive technology is frequently inefficacious in cases of ovarian ageing, thus raising the economic, medical and societal costs of the procedures. OBJECTIVE AND RATIONAL: Ovarian ageing is characterized by quantitative and qualitative alteration of the ovarian oocyte reserve. Mitochondria play a central role in follicular atresia and could be the main target of the ooplasmic factors determining oocyte quality adversely affected by ageing. Indeed, the oocyte is the richest cell of the body in mitochondria and depends largely on these organelles to acquire competence for fertilization and early embryonic development. Moreover, the oocyte ensures the uniparental transmission and stability of the mitochondrial genome across the generations. This review focuses on the role played by mitochondria in ovarian ageing and on the possible consequences over the generations. SEARCH METHODS: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning mitochondria and ovarian ageing, in animal and human species. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA'; 'ovarian reserve', 'oocyte', 'ovary' or 'cumulus cells'; and 'ageing' or 'ovarian ageing'. These keywords were combined with other search phrases relevant to the topic. References from these articles were used to obtain additional articles. OUTCOMES: There is a close relationship, in mammalian models and humans, between mitochondria and the decline of oocyte quality with ageing. Qualitatively, ageing-related mitochondrial (mt) DNA instability, which leads to the accumulation of mtDNA mutations in the oocyte, plays a key role in the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality. WIDER IMPLICATIONS: A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future. PMID- 27562291 TI - Magneto-elasto-electroporation (MEEP): In-vitro visualization and numerical characteristics. AB - A magnetically controlled elastically driven electroporation phenomenon, or magneto-elasto-electroporation (MEEP), is discovered while studying the interactions between core-shell magnetoelectric nanoparticles (CSMEN) and biological cells in the presence of an a.c. magnetic field. In this paper we report the effect of MEEP observed via a series of in-vitro experiments using core (CoFe2O4)-shell (BaTiO3) structured magnetoelectric nanoparticles and human epithelial cells (HEP2). The cell electroporation phenomenon and its correlation with the magnetic field modulated CSMEN are described in detail. The potential application of CSMEN in electroporation is confirmed by analyzing crystallographic phases, multiferroic properties of the fabricated CSMEN, influences of d.c. and a.c. magnetic fields on the CSMEN and cytotoxicity tests. The mathematical formalism to quantitatively describe the phenomena is also reported. The reported findings provide insights into the underlying MEEP mechanism and demonstrate the utility of CSMEN as an electric pulse-generating nano-probe in electroporation experiments with a potential application toward accurate and efficient targeted cell permeation. PMID- 27562292 TI - Application of human factors engineering (HFE) to the design of a naloxone auto injector for the treatment of opioid emergencies. AB - The increased use of opioids for chronic treatment of pain and the resulting epidemic of opioid overdoses have created a major public health challenge. Parenteral naloxone has been used since the 1970's to treat opioid overdose. Recently, a novel naloxone auto-injector device (EVZIO, kaleo, Inc., Richmond, VA) was approved by the Food and Drug Administration. In this article, we review the Human Factors Engineering (HFE) process used in the development and testing of this novel naloxone auto-injector currently used in nonmedical settings for the emergency treatment of known or suspected opioid overdose. HFE methods were employed throughout the product development process for the naloxone auto injector including formative and summative studies in order to optimize the auto injector's user interface, mitigate use-related hazards and increase reliability during an opioid emergency use scenario. HFE was also used to optimize the product's design and user interface in order to reduce or prevent user confusion and misuse. The naloxone auto-injector went through a rigorous HFE process that included perceptual, cognitive, and physical action analysis; formative usability evaluations; use error analysis and summative design validation studies. Applying HFE resulted in the development of a product that is safe, fast, easy and predictably reliable to deliver a potentially life-saving dose of naloxone during an opioid overdose emergency. The naloxone auto-injector may be considered as a universal precaution option for at-risk patients prescribed opioids or those who are at increased risk for an opioid overdose emergency. PMID- 27562293 TI - Assessing the effect of a nude mouse model on nanoparticle-mediated gene delivery. AB - The relevance of using nude mouse models for evaluating drug delivery to human tumors has recently been questioned by numerous researchers. While the immune response is known to play a critical role in cancer, this study assesses the effect of using immunocompromised "nude" mice on drug delivery. By inoculating both nude and immunocompetent mice with a mouse mammary carcinoma cell line (4T1), differences in the "first pass effect", distribution, and reporter gene expression due to the use of the nude mouse model could be elucidated. Our results indicate that initial tumor deposition (5 min) was slightly lower in nude mice but comparable after 24 h. In addition, some small differences in tissue deposition/accumulation and reporter gene expression were observed between the two mouse models. The results with this one tumor model suggest that delivery studies conducted in nude mice can provide comparable results to those in immunocompetent mouse models. PMID- 27562294 TI - Novel in situ forming hydrogel microneedles for transdermal drug delivery. AB - Novel in situ forming hydrogel microneedles were evaluated for transdermal drug delivery using a biocompatible non-ionic triblock amphiphilic thermosensitive copolymer. The transition property of poloxamer from solution at room temperature to gel at skin temperature (32 degrees C) was utilized in preparation of in situ forming hydrogel microneedles. Methotrexate has been used to treat solid tumors, but because of its narrow safety margin, it requires sustained delivery within the therapeutic window. Formulations with and without poloxamer at different methotrexate concentrations were prepared and evaluated for drug permeation across skin using vertical Franz diffusion cell for 72 h. Sol-gel transition, skin resistance and thickness, microneedles geometry, microchannel depth, shape, formation and uniformity, viscoelasticity of skin, and in vitro drug permeation were characterized and tested. An average cumulative drug amount of 32.2 +/- 15.76 and 114.54 +/- 40.89 MUg/cm2 for porcine ear skin and 3.89 +/- 0.60 and 10.27 +/- 6.98 MUg/cm2 for dermatomed human skin from 0.2 % w/w and 0.4 % w/w methotrexate formulations was delivered by the in situ forming hydrogel microneedles. These in situ hydrogel microneedles embedded within the porated site of the skin provided a steady and sustained drug delivery. PMID- 27562296 TI - Erratum to: Variables associated with physical health-related quality of life in Parkinson's disease patients presenting for deep brain stimulation. PMID- 27562295 TI - l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells. AB - BACKGROUND: Asthma is associated with reduced systemic levels of l-arginine and increased asymmetric dimethylarginine (ADMA). This imbalance leads to nitric oxide synthase (NOS) uncoupling with reduced nitric oxide (NO) formation and greater oxidative and nitrosative stress. Whether this imbalance also occurs in bronchial epitheliumof asthmatics is unknown. OBJECTIVES: We used primary human bronchial epithelial cells (HBECs) from asthmatics and healthy controls to evaluate: (i) ADMA-mediated NOS uncoupling reduces epithelial production of NO and increases oxygen and nitrogen reactive species, and (ii) l-citrulline can reverse this mechanism by recoupling NOS, restoring NO production and reducing oxidative and nitrosative stress. RESULTS: In HBECsIL-13 and INFgamma stimulated NOS2 and increased NOx levels. The addition of ADMA reduced NOx and increased H2 O2 levels (p<0.001). Treatment with l-citrulline (800, 1600 MUm) rescued NOx when the l-arginine media concentration was 25 MUm but failed to do so with higher concentrations (100 MUm). Under reduced l-arginine media conditions, HBECs treated with l-citrulline increased the levels of argininosuccinate, an enzyme that metabolizes l-citrulline to l-arginine. l-citrulline prevented the ADMA mediated increase in nitrotyrosine in HBECs in cells from asthmatics and controls. CONCLUSIONS AND CLINICAL RELEVANCE: Increasing ADMA reduces NO formation and increases oxidative and nitrosative stress in airway epithelial cells. l-citrulline supplementation restores NO formation, while preventing nitrosative stress. These results, suggest that l-citrulline supplementation may indeed be a powerful approach to restore airway NO production and may have a therapeutic potential in diseases in which there is a defective production of NO. PMID- 27562297 TI - Biochemical and structural characterization of the novel sialic acid-binding site of Escherichia coli heat-labile enterotoxin LT-IIb. AB - The structurally related AB5-type heat-labile enterotoxins of Escherichia coli and Vibrio cholerae are classified into two major types. The type I group includes cholera toxin (CT) and E. coli LT-I, whereas the type II subfamily comprises LT-IIa, LT-IIb and LT-IIc. The carbohydrate-binding specificities of LT IIa, LT-IIb and LT-IIc are distinctive from those of cholera toxin and E. coli LT I. Whereas CT and LT-I bind primarily to the GM1 ganglioside, LT-IIa binds to gangliosides GD1a, GD1b and GM1, LT-IIb binds to the GD1a and GT1b gangliosides, and LT-IIc binds to GM1, GM2, GM3 and GD1a. These previous studies of the binding properties of type II B-subunits have been focused on ganglio core chain gangliosides. To further define the carbohydrate binding specificity of LT-IIb B subunits, we have investigated its binding to a collection of gangliosides and non-acid glycosphingolipids with different core chains. A high-affinity binding of LT-IIb B-subunits to gangliosides with a neolacto core chain, such as Neu5Gcalpha3- and Neu5Acalpha3-neolactohexaosylceramide, and Neu5Gcalpha3- and Neu5Acalpha3-neolactooctaosylceramide was detected. An LT-IIb-binding ganglioside was isolated from human small intestine and characterized as Neu5Acalpha3 neolactohexaosylceramide. The crystal structure of the B-subunit of LT-IIb with the pentasaccharide moiety of Neu5Acalpha3-neolactotetraosylceramide (Neu5Ac-nLT: Neu5Acalpha3Galbeta4GlcNAcbeta3Galbeta4Glc) was determined providing the first information for a sialic-binding site in this subfamily, with clear differences from that of CT and LT-I. PMID- 27562298 TI - Variations in supportive care needs of patients after diagnosis of localised cutaneous melanoma: a 2-year follow-up study. AB - PURPOSE: We aimed to describe variations in unmet supportive care needs of patients diagnosed with localised melanoma at high risk of recurrence and factors associated with initial and persisting moderate-to-high needs. METHODS: We ascertained 386 patients diagnosed with clinical stage IB-II melanoma and administered surveys every 6 months for 2 years. The proportion experiencing at least one moderate-to-high need was assessed among salient subgroups: 306 patients with no previous melanoma and 80 with previous melanoma at enrolment, 30 who experienced disease recurrence during follow-up and 31 who developed another primary. Baseline factors associated with (a) needs at enrolment and (b) persistent needs over 2 years (or as long as disease-free) were identified by logistic regression analyses. RESULTS: The proportion of patients with needs substantially declined over the first 6 months (if no previous melanoma, from 48 to 22 %, p < 0.001; previous melanoma, 35 to 17 %, p = 0.007), and in those remaining disease-free, needs declined further by 24 months (to 14 and 6 % respectively). By contrast, 50 % of those experiencing recurrence, and 39 % of those who developed another primary, reported needs. Stressful life events and anxiety were associated with needs at enrolment. At least one need, mainly fear of recurrence, persisted in 22 % of disease-free participants. Persistent needs were predicted by age, depression, anxiety and other stressful life events. CONCLUSIONS: Melanoma patients' needs peak when first diagnosed and if disease recurs. Younger people or those experiencing additional stressful events, anxiety or depression are more likely to experience persistent needs and may benefit from tailored support. PMID- 27562304 TI - Non-genetic sources of variation and temporal variability in growth and feed efficiency traits among phylogenetically distinct clusters of indigenous chicken in Kenya. AB - This study aims to investigate the influence of non-genetic factors on feed efficiency in indigenous chicken. Residual feed intake (RFI), residual gain (RG) and residual intake and gain (RIG) were used as measures of feed efficiency. Feed intake and body weight data were collected on 107 experimental birds on a daily and weekly basis, respectively, from ages 11 to 20 weeks. A general linear model was fitted to determine the effect of sex, cluster, genotype and hatch group on mean performance and to assess temporal variation across clusters. The overall mean performance for daily gain (ADG), daily feed intake (ADFI), weekly metabolic body weight (MBW), RFI, RG and RIG was 10.38 g/day, 133.01 g/day, 164.12 g/day, 0.00 (+/-14.23), 0.00 (+/-1.83) and 0.00 (+/-14.64), respectively. Sex significantly influenced variation in ADG and RG while hatch group influenced all traits except ADFI. Cluster and genotype had no effect on the traits. Interaction between sex and cluster significantly influenced ADFI, RFI and RIG. There was a significant temporal variation within and among clusters resulting in re-ranking of the phylogenetic groups in efficiency across the test period. Results indicate that growth and feed efficiency traits are influenced by non-genetic factors which should be accounted for, to reduce bias and improve accuracy of performance evaluations in the indigenous chicken. PMID- 27562303 TI - Supplementation with Ca salts of soybean oil interacts with concentrate level in grazing dairy cows: milk production and milk composition. AB - In this study, we investigated the associative effects of concentrate levels and Ca salts of soybean oil (CSSO) supplementation on milk production, milk composition, and milk fatty acids of mid-lactation dairy cows grazing on tropical pasture. Twenty-four Jersey * Holstein cows were used in a randomized block design and assigned to four treatments arranged in a 2 * 2 factorial design. Factors evaluated were concentrate levels (low, 3 kg/day vs. high, 7 kg/day of concentrate) and CSSO supplementation (without CSSO vs. with 250 g CSSO cow/day). All cows grazed on elephant grass (Pennisetum purpureum cv. Cameroon) and received the supplemental treatments for a 90-day period. Interactions between concentrate level and CSSO were detected for milk yield, milk yield components, energy-corrected milk (ECM) and 3.5 % fat-corrected milk (FCM). Milk yield increased when CSSO was fed in a low concentrate level, while it decreased milk production in a high concentrate level. Yields of fat, protein, lactose, 3.5 % FCM, and ECM were not affected with CSSO in the low concentrate, but reduced in the high concentrate level. CSSO increased proportions of monounsaturated milk FA, C18:2 trans-10 cis-12, and polyunsaturated FA, and reduced proportions of saturated milk FA in milk. In conclusion, feeding the high level of concentrate was an effective strategy to improve milk yield and solid production. CSSO supplementation increased milk production when fed at low concentrate level but did not affect yield of solids. PMID- 27562306 TI - Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells. PMID- 27562307 TI - Response to: Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells. PMID- 27562308 TI - Neurotoxicity of paraquat and paraquat-induced mechanisms of developing Parkinson's disease. PMID- 27562309 TI - Response to: Neurotoxicity of paraquat and paraquat-induced Parkinson's disease. PMID- 27562310 TI - Hypoxia-stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-beta1 signaling pathway. PMID- 27562311 TI - Socio-demographic influences on language structure and change: Not all learners are the same. AB - The Now-or-Never bottleneck has important consequence for understanding why languages have the structures they do. However, not addressed by C&C is that the bottleneck may interact with who is doing the learning: While some languages are mostly learned by infants, others have a large share of adult learners. We argue that such socio-demographic differences extend and qualify C&C's thesis. PMID- 27562312 TI - Equity, barriers and cancer disparities: study of the Spanish Society of Medical Oncology on the access to oncologic drugs in the Spanish Regions. AB - PURPOSE: The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. METHODS: An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. RESULTS: 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. CONCLUSIONS: The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions. PMID- 27562313 TI - Cadaveric validation of a finite element modeling approach for studying scapular notching in reverse shoulder arthroplasty. AB - Cadaveric experiments were undertaken to validate a finite element (FE) modeling approach for studying impingement-related scapular notching in reverse shoulder arthroplasty (RSA). The specific focus of the validation was contact at the site of impingement between the humeral polyethylene component and the inferior aspect of the scapula during an adduction motion. Lateralization of the RSA center of rotation was varied because it has been advocated clinically to reduce impingement and presumably decrease the risk of scapular notching. Tekscan sensors were utilized to directly measure contact stress at the impingement site, and FE was used to compute contact stresses. Favorable agreement was seen between physically measured and FE-computed impingement site location (within one sensing element of the Tekscan sensor) and contact loads (mean absolute difference of 14.9%). Contact stresses and contact areas were difficult to compare directly due to the disparate spatial resolutions of the Tekscan sensor and the FE model. FE computed contact at the impingement site was highly focal, with a total contact area comparable to the area of an individual Tekscan sensing element. The good agreement between the physically measured and FE-computed contact data (i.e., contact load and location) support the use of FE modeling as a tool for computationally testing the efficacy of changing various surgical variables associated with RSA. PMID- 27562314 TI - Mother-infant cultural group selection. AB - Richerson et al. argue that "cultural group selection plays an essential role in explaining human cooperation." We believe that cooperation came first, making culture and thus cultural group selection possible. Cooperation and culture began - and begins - in mother-infant interaction. PMID- 27562315 TI - Non-genetic risk factors in haemophilia A inhibitor management - the danger theory and the use of animal models. AB - In haemophilia A (HA) management, antidrug antibodies, or inhibitors, are a serious complication that renders factor VIII (FVIII) replacement therapy ineffective, increases morbidity and reduces quality of life for affected patients. Inhibitor development aetiology is multifactorial and covers both genetic and therapy related risk factors. Many therapy-related risk factors have proven difficult to confirm due to several confounding factors and the small study populations available. However, clinical studies indicate that e.g. on demand treatment and surgery affect inhibitor development, and explanations for this association are being investigated. A potential explanation is the danger signal effect, where the immune response is activated by endogenous or exogenous danger or damage signals present at the time and site of FVIII administration. The danger theory explains how alarm signals from stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass unnoticed. This role of danger in HA inhibitor formation has previously been suggested, but a thorough discussion of this subject is lacking. The present review will discuss the potential role of danger signals in haemophilia and inhibitor development, with focus on treatment related risk factors with a suspected danger signal aetiology; on-demand treatment, treatment during major bleeds or surgery, and treatment during infection or vaccination. Clinical studies as well as animal experiments addressing these factors will be reviewed. PMID- 27562316 TI - Latitudinal distribution of microbial communities in anaerobic biological stabilization ponds: effect of the mean annual temperature. AB - Considering wide utilization and high methane fluxes from anaerobic biological stabilization ponds (ABSPs), understanding the methanogenesis in ABSPs is of fundamental importance. Here we investigated the variation and impact factors of methanogenesis in seven ABSPs that spanned from the north to the south of China. Results showed that methanogen abundance (7.7 * 109 -8.7 * 1010 copies g-1 dry sediment) and methanogenic activities (2.2-21.2 MUmol CH4 g-1 dry sediment h-1 ) were considerable for all sediments. Statistical analysis demonstrated that compared with other factors (ammonium, pH, COD and TOC), mean annual temperature (MAT) showed the lowest P value and thus was the most important influencing factor for the methanogenic process. Besides, with the increasing MAT, methanogenic activity was enhanced mainly due to the shift of the dominant methanogenic pathway from acetoclastic (49.8-70.7%) in low MAT areas to hydrogenotrophic (42.0-54.6%) in high MAT areas. This shift of methanogenic pathway was also paralleled with changes in composition of bacterial communities. These results suggested that future global warming may reshape the composition of methanogen communities and lead to an increasing methane emission from ABSPs. Therefore, further research is urgently needed to globally estimate methane emissions from ABSPs and re-examine the role of ABSPs in wastewater treatment. PMID- 27562317 TI - Cattell-Braasch maneuver combined with local hypothermia during superior mesenteric artery resection in pancreatectomy. AB - BACKGROUND: The recent development of new neo-adjuvant treatment regimens associated with a higher success rate of down-staging has increased the interest of pancreatic surgeons on the role of extended surgery for patients affected by locally advanced pancreatic cancer. Pancreatectomy together with resection of the portal/superior mesenteric vein is considered nowadays standard of care for patients affected by pancreatic cancer. However, the resection of major abdominal arteries is still debatable. In particular, the short- and long-term results after resection of the superior mesenteric artery (SMA) remain controversial and only few cases have been described in literature. The present paper describes a new, quick, and easy technique for resection of the SMA. CLINICAL CASE: A 71-year old patient affected by IPMN cancer with infiltration of the SMA received FOLFIRINOX-based neo-adjuvant treatment. After 4 months of treatment, the patient underwent total pancreatectomy with en bloc resection of the SMA and direct end to-end anastomosis. The vascular resection was performed combining a complete Cattell-Braasch maneuver with local bowel hypothermia in an attempt to avoid graft interposition by facilitating an end-to-end anastomosis and to reduce the warm ischemia time. The post-operative course was uneventful and the patient was discharged 8 days post-operatively. PMID- 27562318 TI - The convergent and divergent evolution of social-behavioral economics. AB - Human hunter-gatherers share a suite of traits with social insects, which demonstrates convergent social evolution of these taxa prior to agriculture. Humans differ from social insects in that their divisions of labor are more competitive than cooperative. Resulting higher within-group competition in humans has been alleviated by religion and culturally imposed monogamy, both of which also find parallels among social insects. PMID- 27562319 TI - Cerbera manghas methanol extract exerts anti-inflammatory activity by targeting c Jun N-terminal kinase in the AP-1 pathway. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cerbera manghas L. (Apocynaceae) is a medicinal plant traditionally used to ameliorate the clinical signs of inflammatory diseases and hypertension. AIM OF STUDY: Although C. manghas L. has long been used as a traditional remedy for various diseases, the underlying molecular and cellular mechanisms are poorly understood. A detailed investigation of these mechanisms is necessary to demonstrate the ethnopharmaceutical utility of this plant. MATERIALS AND METHODS: The effects of C. manghas methanol extract (Cm-ME) on the production of inflammatory mediators and the expression of proinflammatory cytokines and identification of molecular targets were investigated using lipopolysaccharide (LPS)-treated macrophages in vitro. In addition, the inhibitory effects of Cm-ME orally administered were tested by LPS/D galactosamine (D-GalN)-induced hepatitis and LPS-induced peritonitis mouse models in vivo. RESULTS: Cm-ME downregulated the production of prostaglandin (PG)E2 and the mRNA expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta in LPS-stimulated RAW264.7 cells under non-toxic concentration of Cm-ME. This extract inhibited the nuclear translocation of c-Jun and p-ATF2, the phosphorylation of JNK and p38, and AP-1 activity. Western blot analysis and in vitro kinase assay confirmed that JNK is a direct pharmacological target of Cm-ME action. In addition, Cm-ME significantly ameliorated the clinical signs of LPS/D-GalN-induced hepatitis and lowered the production of nitric oxide (NO) and the phosphorylation of JNK in LPS-induced peritonitis conditions. CONCLUSION: Cm-ME exerts anti-inflammatory actions on LPS-stimulated macrophages and in mouse models of acute inflammatory disease. These actions are predominantly mediated by targeting JNK in the AP-1 signaling pathway. PMID- 27562320 TI - Bufei Yishen granules combined with acupoint sticking therapy suppress oxidative stress in chronic obstructive pulmonary disease rats: Via regulating peroxisome proliferator-activated receptor-gamma signaling. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is clinically used under the guidance of its unique theory system. Bufei Yishen (BY) granules, an oral Chinese herbal formula, is confirmed effective for treating the syndrome of lung-kidney qi deficiency in chronic obstructive pulmonary disease (COPD) patients. Shu-Fei Tie ointment is another prescription for acupoint sticking (AS) therapy based on the theory of treating an internal disease by external treatment on proper acupoints. The beneficial effects of BY granules combined with Shu-Fei Tie have been proved in previous clinical trials. However, the underlying mechanism remains unclear. The present study was initiated to explore the antioxidative mechanism of the integrated therapy of BY granules and acupoint sticking via regulating by peroxisome proliferator activated receptor-gamma (PPARgamma) signaling in a cigarette-smoke/bacterial exposure induced COPD rat model. MATERIALS AND METHODS: Rats were randomized into Control, Model, BY, AS, BY+AS and aminophylline (APL) groups. COPD rats were induced by cigarette-smoke and bacterial exposures, and were administrated with normal saline, BY granules, AS, BY+AS or aminophylline from week 9 and sacrificed at week 20. Activity of superoxide dismutase (SOD) and levels of methane dicarboxylic aldehyde (MDA) in peripheral blood and bronchoalveolar lavage fluid (BALF) were determined by hydroxylamine and thiobarbituric acid methods. The gene and protein expressions of PPARgamma in the lung tissues were analyzed by quantitative polymerase chain reaction and western blot. RESULTS: Serum and BALF SOD decreased significantly in Model group (P<0.01), while MDA increased (P<0.01). Compared to COPD rats, serum SOD was higher in all treatment groups (P<0.01), and BALF SOD was higher in BY and BY+AS groups (P<0.01); serum and BALF MDA was lower in all treatment groups (P<0.01). Serum and BALF SOD was higher in BY+AS group than in AS group, while MDA was lower (P<0.05). BALF SOD increased in BY+AS group compared with APL group, while MDA decreased (P<0.05). PPARgamma mRNA and protein and the phosphorylation of PPARgamma (p-PPARgamma) decreased in COPD rats (P<0.01), and increased in all treatment groups (P<0.01). PPARgamma mRNA was higher in BY+AS group than in AS group (P<0.05), PPARgamma and p-PPARgamma were higher in BY+AS group than in AS and APL groups (P<0.05, P<0.01); PPARgamma protein was higher in BY group than in APL group (P<0.05). CONCLUSION: Bufei Yishen granules, Shu-Fei Tie and their combination have beneficial effects in stable COPD, and can attenuate the oxidative stress, and the activation of PPARgamma signaling might be involved in the underlying mechanisms, but there are no obvious synergistic effect of Bufei Yishen granules and Shu-Fei Tie. PMID- 27562321 TI - MicroRNA-146a and miR-99a are potential biomarkers for disease activity and clinical efficacy assessment in psoriasis patients treated with traditional Chinese medicine. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a common chronic inflammatory skin disease. A number of clinical investigations have indicated that traditional Chinese medicine (TCM) is an effective and safe treatment for psoriasis. Zhuhuang Granule (ZG) is a modified formulation of Zhuhuang Decoction, which is used traditionally in China for the treatment of psoriasis in clinical practice. AIM OF THE STUDY: Recent studies have found that microRNAs (miRNAs) play important roles in the pathogenesis of some skin diseases. The objective of our study was to investigate the effect of ZG on the expression of miRNAs in peripheral blood mononuclear cells (PBMCs) from psoriasis patients and to identify specific miRNA biomarkers for psoriasis disease activity and assessment of clinical efficacy. MATERIALS AND METHODS: Twenty-five psoriasis patients and 15 healthy control subjects were recruited to participate in this study from October 2013 to October 2014. Microarray and quantitative real-time PCR (qRT-PCR) were used to measure the global miRNA expression in PBMCs from psoriasis patients and healthy control subjects. We also measured the changes in the Psoriasis Area and Severity Index (PASI) score and miRNA expression of patients before and after treatment with ZG. RESULTS: The microarray results showed that 26 miRNAs were upregulated and 13 miRNAs were decreased in psoriasis patients. qRT-PCR validated 3 upregulated miRNAs (miR-146a, miR-31, miR-192-5p) and 2 downregulated miRNAs (miR-99a, miR 200c) in PBMCs from psoriasis patients compared with healthy controls (p<0.01). Moreover, after 8 weeks of ZG treatment, patients achieved a significant reduction in PASI scores. QRT-PCR analysis indicated that the expression of miR 146a and miR-99a is closely correlated with psoriasis severity (R2=0.772, p<0.01; R2=0.672, p<0.01). CONCLUSION: We suggest that both miR-146a and miR-99a may serve as potential biomarkers for disease activity and clinical efficacy in psoriasis patients treated with ZG. PMID- 27562322 TI - DNA methylation signature of intergenic region involves in nucleosome remodeler DDM1-mediated repression of aberrant gene transcriptional read-through. AB - The strict and efficient transcription termination is required to prevent production of aberrant read-through transcripts that may cause transcriptional interference at neighboring genes. However, the exact regulatory mechanism remains poorly understood. Through a genetic screening of a LUCIFERASE (LUC) reporter system, we found that Arabidopsis nucleosome remodeler DECREASE IN DNA METHYLATION1 (DDM1) is a key component of this regulatory machinery and plays an important role in transcription termination, thus limiting transcriptional read through (TRT). By whole-genome strand-specific RNA sequencing, we identified and confirmed 43 endogenous TRTs between genes, transposable elements (TEs), or genes and TEs in the ddm1-10 mutant, which mainly occurred at heterochromatin regions. The DNA methylation analysis of these TRT regions revealed that TRT occurred frequently at the intergenic regions with a higher methylation level in wild type comparing to the regions where TRT did not occur. Our results suggest that the level of intergenic DNA methylation may involve in preventing aberrant gene TRT or producing new gene during evolution. PMID- 27562323 TI - Small scale water treatment practice and associated factors at Burie Zuria Woreda Rural Households, Northwest Ethiopia, 2015: cross sectional study. AB - BACKGROUND: Consuming unsafe water results in infections that lead to illness or death from water borne diseases. Though there is an increasing effort from Ethiopian government to access safe water still there are households with limited access of safe water as a result, they depend on rain, well and spring water source for domestic use. However, the water treatment practice with the available technology is not studied before in the study area. This study was conducted in rural area where there was no improved water source for domestic consumption. Households' access water from rain, spring, river and well water which need some ways of action to make water safe for the intended utilization termed as treatment. Hence, the aim of this study was to assess magnitude of small scale water treatment practices and associated factors at household level in Burie zuria woreda, North West Ethiopia, 2015. METHODS: Community based cross-sectional study design with multi-stage sampling technique was used to evaluate water treatment practice and associated factors among rural households in Burie Zuria Woreda. A total of 797 households included in the study. Completeness of questionnaires were checked daily and data were coded and entered into Epi-Data and transported to SPSS version 16 software package for further analysis. Binary and multivariable logistic regression models fit to identify associated factors at 95 % CI and P-value <0.05. RESULT: A total of 797 out of 846 participants responded to a questionnaire with a response rate of 94.2 %. The mean age of respondents was 44.9(SD +/-10.7) years. Among the total study participants, 357(44.8 %) of them were practicing small scale water treatment at household level. Methods of water treatment at household level were; chlorine, boiling and let stand and settle. Associated factors were female headed households practice water treatment than male headed households (AOR = 1.80, 95 % CI = 1.24-2.62), educational status of being literate was associated with water treatment than illiterates (AOR = 2.07, 95 % CI = 1.51-2.83), dipping of water was associated with water treatment practice than pouring from the water collection jar (AOR = 4.11, 95 % CI = 2.89-5.85) and those households more frequently fetch water were practicing water treatment than those fetch less frequently (AOR = 4.90, 95 % CI = 2.92-8.22) and (AOR = 3.76, 95 % CI = 1.97-7.18) respectively were found to be significantly associated with small scale water treatment practice at household level. CONCLUSIONS: Small scale water treatment at household level is still low in the study area. Females headed households, educated people, dipping from the jar and those who fetch water more than twice a day were significant factors for water treatment. Therefore females' practice should be maintained and scale up for male headed households. Those with no primary education need special emphasis to educate them on the importance of water treatment. Encourage education through non formal mechanisms for rural people are also recommended. PMID- 27562324 TI - "Process and perish" or multiple buffers with push-down stacks? AB - This commentary raises two issues: (1) Language processing is hastened not only by internal pressures but also externally by turn-taking in language use; (2) the theory requires nested levels of processing, but linguistic levels do not fully nest; further, it would seem to require multiple memory buffers, otherwise there's no obvious treatment for discontinuous structures, or for verbatim recall. PMID- 27562325 TI - CD200R, a co-inhibitory receptor on immune cells, predicts the prognosis of human hepatocellular carcinoma. AB - The inhibitory CD200:CD200 receptor axis is essential in preventing inflammatory responses during early microbial infection. It was reported in several tumor models that CD200 expression is closely associated to tumor progression and the blockade of this pathway may restore anti-tumor responses. Our study for the first time investigates the role of CD200:CD200R axis in relation to tumor progression and prognosis of human hepatocellular carcinoma. CD200 and CD200R protein expressions were evaluated by immunostaining on liver tissue specimens and we found higher expressions of CD200 and CD200R in HCC patients comparing to healthy controls. CD200 expresses in peritumoral, peritumoral stroma and intratumoral regions of HCC while CD200R predominantly expresses in peritumoral stroma. Furthermore, protein intensity of CD200R is positively associated to the diameter of tumor and alpha-fetoprotein level, in addition, patients with higher pathological grade and absence of tumor capsule exhibit higher CD200R expression. CD200R predominantly expresses on infiltrating macrophages and may associate with liver injury. Moreover, both overall and recurrence-free survival rates are significantly lower in patients with high CD200R expression comparing to those with low CD200R expression. Our findings suggest a promising role of CD200R as a prognostic marker in predicting elevated recurrence and reduced survival, and a potential therapeutic target in treating hepatocellular carcinoma. PMID- 27562326 TI - Matrine downregulates IL-33/ST2 expression in the central nervous system of rats with experimental autoimmune encephalomyelitis. AB - Interleukin (IL)-33 is a recently described member of the IL-1 family and functions as a ligand for ST2, a member of the IL-1 receptor family. The role of IL-33/ST2 axis in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), remains controversial. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, the underlying immunoregulatory mechanisms have not been fully elucidated, and whether this effect of MAT is through inhibiting the function of the IL-33/ST2 axis is not known. In this study, we investigated the relationship between the therapeutic effects of MAT and IL-33/ST2 expression. MAT treatment successfully attenuated severe clinical deficit and histopathological changes, compared to untreated controls. While IL-33/ST2 mRNA expression was largely increased in spinal cord of EAE rats compared to naive rats, this expression was significantly inhibited in rats treated with MAT. These results were further confirmed by their protein levels tested with immunohistochemistry. Together, our study demonstrates that MAT treatment regulates the inflammatory IL-33/ST2 axis, thus being a novel mechanism underlying the effect of MAT. PMID- 27562327 TI - The Doctor of Medicine curriculum review at the School of Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania: a tracer study report from 2009. AB - BACKGROUND: The School of Medicine (SoM) is one among five at Muhimbili University of Health and Allied Sciences (MUHAS). It currently houses eight undergraduate and many post-graduate programmes. The Doctor of Medicine (MD) programme reported herein is the oldest having ten semesters (5 years) followed by a 1 year compulsory rotatory internship at a hospital approved by the Medical Council of Tanganyika (MCT). However, this training was largely knowledge-based and thus the need to shift towards competency-based education (CBE) and full modularization necessitated this study. METHODS: A cross-sectional tracer study of MUHAS MD graduates from SoM who completed training between 2006 and 2008 was conducted using quantitative (structured interviewer-administered questionnaires) as well as qualitative methods [In-depth questionnaire (IDI) and Focus group discussions (FGDs)]. RESULTS: A total of 147 MD graduates were traced and interviewed, representing 29 % of the 510 students who graduated from the SoM between 2006 and 2008. Majority (70.1 %, n = 103/147) were males. About 70 % graduated in 2008 and majority (68 %, n = 100/147) were doing internship. Majority (60.5 % n = 89/147) were based in/near Dar es Salaam at district, regional or referral hospitals. With reasonable concordance, most competencies ranked low except on four aspects. Teaching, System-based Practice and Good Practice had the lowest. Seminars/Tutorials, Laboratory Skills/Practicals, Theatre Skills, Outpatients clinics, Family Case Studies, Visits/Excursions and Self Reflection were rated less useful teaching methods compared to Lectures, Teaching Ward Rounds, Elective Studies, Field Work, Presentations, Continuous Assessments Tests, Final Examinations, Short Answers, Clinical/Practical Examinations. ICT and Library facilities were not considered to meet the students learning needs and Clinical Logbooks also ranked low. Teachers were generally ranked less favorably including in professional role-modelling and accessibility outside scheduled teaching sessions. CONCLUSIONS: This tracer study results allowed subsequent curriculum review and the introduction of full modularization and competency-based learning at MUHAS. It is envisioned that these tracer study findings will improve teaching, learning and inform next curriculum review at MUHAS leading to increased output of appropriately trained health professionals to fill the big gap in human resources for health (HRH) in Tanzania. The revised curricula are also being processed through TCU for accreditation as required. PMID- 27562328 TI - Atypical Location of a Thymoma. PMID- 27562329 TI - High Flow Therapy in Post-Lung Transplant Patients. PMID- 27562330 TI - [Pasteurella multocida cellulitis after cat bite and subsequent erythema nodosum]. PMID- 27562331 TI - [Current aspects of prostate cancer screening]. AB - Screening programs for prostate cancer based on the determination of serum prostate specific antigen has led to overdiagnosis, and consequently overtreatment. A percentage of men diagnosed with prostate cancer have a tumour that will not progress, or do so slowly (overdiagnosis or pseudo-disease). This overdiagnosis rate ranges from 17-50%. Mass screening is defined as the systematic examination of asymptomatic men. Early detection or opportunistic screening involves the pursuit of individual cases being initiated by the doctor or the patient. In the case of a patient who requests a prostate specific antigen from their general practitioner, a number of issues on overdiagnosis, over treatment and possible damage from the biopsy, should be explained to him. With data from randomised studies on prostate specific antigen and prostate cancer screening, population screening is not recommended by any urological society. PMID- 27562332 TI - Psychoanalysis and the law. AB - The paper discusses Freud's view of the law as the implementation of collective violence on the individual violator. I focus on the implications of the link between the superego (as the source of moral judgment) and the aggressive drive and suggest that we need to be ever vigilant regarding the danger of employing the law as a disguised means of taking pleasure in collective violence. The paper also discusses Freud's conception of personal responsibility, according to which we are responsible for all our behavior, including unconsciously motivated behavior (such as slips and dreams). However, the kind of responsibility Freud has in mind is not the moral responsibility of blameworthiness or praiseworthiness, but rather responsibility in the sense that, whether or not acknowledged, all our behavior reflects our personal desires and motives. PMID- 27562333 TI - Contribution of mexAB-oprM and mexXY (-oprA) efflux operons in antibiotic resistance of clinical Pseudomonas aeruginosa isolates in Tabriz, Iran. AB - Overexpression of efflux pumps is one of the most important mechanisms that contributes to intrinsic and acquired resistance to antibiotics in Pseudomonas aeruginosa. The present study evaluated the role of MexAB-OprM and MexXY (-OprA) efflux pump overexpression in antibiotics resistance of P. aeruginosa clinical isolates. One-hundred clinical isolates of P. aeruginosa were obtained from four hospitals of Tabriz city in Northwest Iran. Isolates were identified and evaluated by the disk diffusion method and agar dilution in order to determine antibiotic resistance. Effect of Phenylalanine Arginine beta-Naphthylamide (PAbetaN) on susceptibility to various anti-Pseudomonas antimicrobials and expression levels of mexB and mexY using quantitative real-time PCR were determined in the clinical isolates. Random Amplified Polymorphic DNA Typing (RAPD-PCR) was used for genotyping of the isolates. The most and least effective antibiotics tested were colistin and ofloxacin, respectively. Seventy-one percent of the isolates were found as multidrug resistant (resistant to at least three different classes of antibiotics). Among ciprofloxacin and levofloxacin resistant isolates, 39.6% and 28.5% of them showed four-fold reduction in MIC with PAbetaN, respectively. Sixty-two percent and 65% of isolates overexpressed mexB and mexY, respectively. Sixty six isolates showed overexpression of both mexB and mexY efflux genes. Moreover, 76% and 88.7% of MDR isolates were mexB and mexY overexpressed, respectively. There were 30 different RAPD types in this study which were clustered into 6 clones. The study indicated that there is a significant correlation between the expression of efflux pumps and the resistance to most anti-pseudomonal antibiotics. PMID- 27562334 TI - Dynamic changes of Plasmodium vivax population structure in South Korea. AB - The vivax malaria epidemic has persisted in South Korea since its reemergence in 1993. Although there has been a significant decrease in the number of malaria cases in recent years, vivax malaria is still a major public health concern. To gain in-depth insight into the genetic makeup of Korean Plasmodium vivax, we analyzed polymorphic patterns of two major antigens, merozoite surface protein-1 (MSP-1) and MSP-3alpha, in 255 Korean P. vivax isolates collected over an extended period from 1998 to 2013. Combinational genetic analysis of polymorphic patterns of MSP-1 and MSP-3alpha in the isolates suggests that the P. vivax population in South Korea has been diversifying rapidly, with the appearance of parasites with new genotypes, despite the recent reduction of disease incidence. These results highlight the importance of molecular epidemiological investigations to supervise the genetic variation of the parasite in South Korea. PMID- 27562335 TI - Dopaminergic inhibition by G9a/Glp complex on tyrosine hydroxylase in nerve injury-induced hypersensitivity. AB - The neural balance between facilitation and inhibition determines the final tendency of central sensitization. Nerve injury-induced hypersensitivity was considered as the results from the enhanced ascending facilitation and the diminished descending inhibition. The role of dopaminergic transmission in the descending inhibition has been well documented, but its underlying molecular mechanisms are unclear. Previous studies demonstrated that the lysine dimethyltransferase G9a/G9a-like protein (Glp) complex plays a critical role in cocaine-induced central plasticity, and given cocaine's role in the nerve system is relied on its function on dopamine system, we herein proposed that the reduced inhibition of dopaminergic transmission was from the downregulation of tyrosine hydroxylase expression by G9a/Glp complex through methylating its gene Th After approval by the Animal Care and Use Committee, C57BL/6 mice were used for pain behavior using von Frey after spared nerve injury, and Th CpG islands methylation was measured using bisulfite sequencing at different nerve areas. The inhibitor of G9a/Glp, BIX 01294, was administered intraventricularly daily with bolus injection. The protein levels of G9a, Glp, and tyrosine hydroxylase were measured with immunoblotting. Dopamine levels were detected using high-performance liquid chromatography. The expression of G9a but not Glp was upregulated in ventral tegmental area at post-injury day 4 till day 49 (the last day of the behavioral test). Correspondingly, the Th CpG methylation is increased, but the tyrosine hydroxylase expression was downregulated and the dopamine level was decreased. After the intracerebroventriclar injection of BIX 01294 since the post-injury days 7 and 14 for consecutive three days, three weeks, and six weeks, the expression of tyrosine hydroxylase was upregulated with a significant decrease in Th methylation and increase in dopamine level. Moreover, the pain after G9a/Glp inhibitor was attenuated significantly. In sum, methytransferase G9a/Glp complex partially controls dopaminergic transmission by methylating Th in peripheral nerve injury-induced neuropathic pain. PMID- 27562336 TI - Precision Fluid Management in Continuous Renal Replacement Therapy. AB - Fluid management during continuous renal replacement therapy (CRRT) in critically ill patients is a dynamic process that encompasses 3 inter-related goals: maintenance of the patency of the CRRT circuit, maintenance of plasma electrolyte and acid-base homeostasis and regulation of patient fluid balance. In this article, we report the consensus recommendations of the 2016 Acute Disease Quality Initiative XVII conference on 'Precision Fluid Management in CRRT'. We discuss the principles of fluid management, describe various prescription methods to achieve circuit integrity and introduce the concept of integrated fluid balance for tailoring fluid balance to the needs of the individual patient. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for fluid management in patients undergoing CRRT. Finally, we identify and highlight areas of uncertainty in fluid management and set an agenda for future research. PMID- 27562338 TI - Cell-Free Placental DNA in Maternal Plasma in Relation to Placental Health and Function. AB - BACKGROUND: While cell-free placental DNA (cfp-DNA) increases in response to certain pathological conditions, confounding variables, such as placental size, may also contribute to its release. Furthermore, the relationship between cfp-DNA and maternal serum proteins has not been well investigated. OBJECTIVE: To analyze plasma cfp-DNA levels and correlate with measurable placental parameters, maternal serum proteins, or pathologic conditions reflecting placental dysfunction. METHOD: Methylated fraction of RASSF1A was quantified in maternal plasma as a measure of cfp-DNA in a cohort of 86 pregnant women. RESULTS: Placental dimensions or weight had no impact on cfp-DNA levels in noncomplicated pregnancies (n = 63). However, an association between beta-hCG and cfp-DNA levels (p = 0.0012) was detected. Complications occurred in 23 pregnancies including chromosomal abnormalities, gestational hypertension, intrauterine growth restriction, and preterm birth. There was overall a skewed distribution (<-1 SD or >1 SD from mean) for cfp-DNA in the abnormal group, although due to the small number of samples for each pathology, we provide only descriptive data to assess possible trends in cfp-DNA variation. CONCLUSION: While cfp-DNA levels outside of the normal range may reflect placental distress, this relationship may be masked by a number of physiological confounders. The independence of cfp-DNA from beta hCG levels commonly assessed in pregnancy need to be further addressed. PMID- 27562337 TI - Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis. AB - Sphingolipids (SL) are both fundamental structural components of the eukaryotic membranes and signaling molecules that regulate a variety of biological functions. The highly-bioactive lipids, ceramide and sphingosine-1-phosphate, have emerged as important regulators of cardiovascular function in health and disease. In this review we discuss recent insights into the role of SLs, particularly ceramide and sphingosine-1-phosphate, in the pathophysiology of the cardiovascular system. We also highlight advances into the molecular mechanisms regulating serine palmitoyltransferase, the first and rate-limiting enzyme of de novo SL biosynthesis, with an emphasis on the recently discovered inhibitors of serine palmitoyltransferase, ORMDL and NOGO-B proteins. Understanding the molecular mechanisms regulating this biosynthetic pathway may lead to the development of novel therapeutic approaches for the treatment of cardiovascular diseases. PMID- 27562339 TI - Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer. AB - BACKGROUND: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life threatening complications. METHODS: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive lung cancer patients with brain metastases. RESULTS: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p < 0.001 and p < 0.001, respectively). There was a positive correlation between the size of metastasis and the thickness of peritumoral brain edema (p < 0.001). It was thicker in supratentorial tumors (p = 0.019), in younger patients (<=50 years) (p = 0.042), and in females (p = 0.016). The time to development of brain metastasis was shorter in central than in peripheral lung cancer (5.3 vs. 9.0 months, p = 0.035). Early brain metastasis was characteristic for adenocarcinomas. A total of 135 patients had brain only metastases (N0 disease) characterized by peripheral lung cancer predominance (p < 0.001) and a longer time to development of brain metastasis (9.2 vs. 4.4 months, p < 0.001). OS was longer in the brain only subgroup than in patients with N1-3 diseases (p < 0.001). CONCLUSIONS: The clinicopathological characteristics of lung cancer are related to the development and radiographic features of brain metastases. Our results might be helpful in selecting patients who might benefit from prophylactic cranial irradiation. PMID- 27562340 TI - How tissue damage MET metabolism: Regulation of the systemic damage response. AB - Living organisms experience tissue damage from both, the surrounding environment and from inside their bodies. Tissue repair/regeneration is triggered by local tissue injury to restore an injured, or lost, part of the body. Tissue damage results in a series of responses, not only locally but also systemically in distant tissues. In our recent publication, we established a "dual system" that induces spatiotemporal tissue damage simultaneously with gene manipulation in surrounding tissues. With this system, we demonstrated that appropriate regulation of methionine metabolism in the fat body is required for tissue repair in Drosophila wing discs, thus highlighting the importance of systemic damage response (SDR) in tissue repair. This "Extra View" aims to discuss our recent reports that propose methionine metabolism to be an essential part of SDR, together with related topics in several model organisms. PMID- 27562341 TI - Novel synthesized 2, 4-DAPG analogues: antifungal activity, mechanism and toxicology. AB - 2, 4-Diacetylphloroglucinol (2,4-DAPG), a natural phenolic compound, has been investigated in light of its biological activities against plant pathogens. To improve its potential application, fourteen 2,4-DAPG analogous were synthesized through the Friedel-Crafts reaction using acyl chlorides and phloroglucinol. Of the 2,4-DAPG derivatives, MP4 exhibited much higher antifungal activity against Penicillium digitatum and P. italicum, the major pathogenic fungi in citrus fruit, than 2, 4-DAPG in vitro, and significantly inhibited the development of decay in harvested mandarin (Citrus reticulata Blanco cv. Shatang.) fruit in vivo. It was found that MP4 resulted in the wrinkle of the hyphae in both fungi with serious folds and breakage. In addition, the expression of several cytochrome P450 (CYP) genes were also modified in both fungi by MP4, which might be associated with the disorder of cell membrane formation. Furthermore, the toxicology of MP4 by evaluating the cell proliferation effect on human normal lung epithelial (16HBE) and kidney 293 (HEK293) cells, was significantly lower than that of albesilate, a widely used fungicide in harvested citrus fruit. In summary, the synthesized MP4 has shown a great potential as a novel fungicide that might be useful for control of postharvest decay in citrus fruit. PMID- 27562342 TI - International Meniscus Reconstruction Experts Forum (IMREF) 2015 Consensus Statement on the Practice of Meniscal Allograft Transplantation. AB - Meniscal allograft transplantation (MAT) has become relatively commonplace in specialized sport medicine practice for the treatment of patients with a symptomatic knee after the loss of a functional meniscus. The technique has evolved since the 1980s, and long-term results continue to improve. However, there still remains significant variation in how MAT is performed, and as such, there remains opportunity for outcome and graft survivorship to be optimized. The purpose of this article was to develop a consensus statement on the practice of MAT from key opinion leaders who are members of the International Meniscus Reconstruction Experts Forum so that a more standardized approach to the indications, surgical technique, and postoperative care could be outlined with the goal of ultimately improving patient outcomes. PMID- 27562343 TI - The multi-omic landscape of transcription factor inactivation in cancer. AB - BACKGROUND: Hypermethylation of transcription factor promoters bivalently marked in stem cells is a cancer hallmark. However, the biological significance of this observation for carcinogenesis is unclear given that most of these transcription factors are not expressed in any given normal tissue. METHODS: We analysed the dynamics of gene expression between human embryonic stem cells, fetal and adult normal tissue, as well as six different matching cancer types. In addition, we performed an integrative multi-omic analysis of matched DNA methylation, copy number, mutational and transcriptomic data for these six cancer types. RESULTS: We here demonstrate that bivalently and PRC2 marked transcription factors highly expressed in a normal tissue are more likely to be silenced in the corresponding tumour type compared with non-housekeeping genes that are also highly expressed in the same normal tissue. Integrative multi-omic analysis of matched DNA methylation, copy number, mutational and transcriptomic data for six different matching cancer types reveals that in-cis promoter hypermethylation, and not in cis genomic loss or genetic mutation, emerges as the predominant mechanism associated with silencing of these transcription factors in cancer. However, we also observe that some silenced bivalently/PRC2 marked transcription factors are more prone to copy number loss than promoter hypermethylation, pointing towards distinct, mutually exclusive inactivation patterns. CONCLUSIONS: These data provide statistical evidence that inactivation of cell fate-specifying transcription factors in cancer is an important step in carcinogenesis and that it occurs predominantly through a mechanism associated with promoter hypermethylation. PMID- 27562345 TI - Pioneers in Pediatric Psychology: Smashing Silos and Breaking Boundaries. AB - As part of the Pioneers in Pediatric Psychology series, this article provides a brief personal account of my career as a pediatric psychologist. Educational and professional experiences often involved confrontations with silos and boundaries set by traditions limiting understanding and impact on children's healthy development. A pedigree in developmental psychology clashed with identity, guild, and loyalty dimensions of clinical psychology. A research emphasis challenged the emergent harmony of the scientist-practitioner models. The medical center and its silos collided with those of arts and sciences academia. Evolving as an applied developmental scientist specializing in pediatric psychology allowed for a gratifying and meaningful career with a range of scientific, pedagogical, and policy contributions. An abiding orientation toward human rights and social justice sustained progress and generativity. PMID- 27562344 TI - Microtubule-based force generation. AB - Microtubules are vital to many important cell processes, such as cell division, transport of cellular cargo, organelle positioning, and cell migration. Owing to their diverse functions, understanding microtubule function is an important part of cell biological research that can help in combating various diseases. For example, microtubules are an important target of chemotherapeutic drugs such as paclitaxel because of their pivotal role in cell division. Many functions of microtubules relate to the generation of mechanical forces. These forces are generally either a direct result of microtubule polymerization/depolymerization or generated by motor proteins that move processively along microtubules. In this review, we summarize recent efforts to quantify and model force generation by microtubules in the context of microtubule function. WIREs Nanomed Nanobiotechnol 2017, 9:e1428. doi: 10.1002/wnan.1428 For further resources related to this article, please visit the WIREs website. PMID- 27562346 TI - Commentary: Integrated Pediatric Primary Care: Moving From Why to How. AB - Whether to address behavioral health issues in pediatric primary care is no longer debated; instead, we are challenged to determine "how" and who can best deliver services in an effective and sustainable manner. This commentary explores how pediatric psychology can contribute to this discussion by developing and evaluating innovative clinical models (such as a hybrid Collaborative Care/Primary Care Behavioral Health model) and expanding workforce and teaching initiatives. PMID- 27562347 TI - High mobility, low access thwarts interventions among seasonal workers in the Greater Mekong Sub-region: lessons from the malaria containment project. AB - BACKGROUND: During the process of malaria elimination in the Greater Mekong Sub region, mobile and migrant populations (MMPs) have been identified as the most at risk demographic. An important sub-group of MMPs are seasonal workers, and this paper presents an evaluation of the reach and effectiveness of interventions tailored towards this group and was carried out as part of the Containment Project from 2009-11. METHODS: A mixed-methods study was conducted in Pailin Province in Western Cambodia. Three-hundred-and-four seasonal workers were surveyed using a structured questionnaire. Qualitative data were gathered through a total of eight focus group discussions and 14 in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis. RESULTS: High mobility and low access of the target population to the interventions, as well as lack of social and anthropological research that led to implementation oversights, resulted in under-exposure of seasonal workers to interventions. Consequently, their reach and impact were severely limited. Some services, particularly Mobile Malaria Workers, had the ability to significantly impact key factors, such as risky behaviours among those they did reach. Others, like Listening and Viewing Clubs and mass media campaigns, showed little impact. CONCLUSIONS: There is potential in two of the interventions assessed, but high mobility and inadequate exposure of seasonal workers to these interventions must be considered in the development and planning of future interventions to avoid investing in low-impact activities and ensure that all interventions perform according to their maximum potential. This will be critical in order for Cambodia to achieve its aim of malaria elimination. The lessons learned from this study can be extrapolated to other areas of health care in Cambodia and other countries in order to reduce the gap between healthcare provided to MMPs, especially seasonal workers, and to the general population. PMID- 27562348 TI - Dielectric barrier discharge atmospheric cold plasma inhibits Escherichia coli O157:H7, Salmonella, Listeria monocytogenes, and Tulane virus in Romaine lettuce. AB - The present study investigated the effects of dielectric barrier discharge atmospheric cold plasma (DACP) treatment on the inactivation of Escherichia coli O157:H7, Salmonella, Listeria monocytogenes, and Tulane virus (TV) on Romaine lettuce, assessing the influences of moisture vaporization, modified atmospheric packaging (MAP), and post-treatment storage on the inactivation of these pathogens. Romaine lettuce was inoculated with E. coli O157:H7, Salmonella, L. monocytogenes (~6logCFU/g lettuce), or TV (~2logPFU/g lettuce) and packaged in either a Petri dish (diameter: 150mm, height: 15mm) or a Nylon/polyethylene pouch (152*254mm) with and without moisture vaporization. Additionally, a subset of pouch-packaged leaves was flushed with O2 at 5% or 10% (balance N2). All of the packaged lettuce samples were treated with DACP at 34.8kV for 5min and then analyzed either immediately or following post-treatment storage for 24h at 4 degrees C to assess the inhibition of microorganisms. DACP treatment inhibited E. coli O157:H7, Salmonella, L. monocytogenes, and TV by 1.1+/-0.4, 0.4+/-0.3, 1.0+/ 0.5logCFU/g, and 1.3+/-0.1logPFU/g, respectively, without environmental modifications of moisture or gas in the packages. The inhibition of the bacteria was not significantly affected by packaging type or moisture vaporization (p>0.05) but a reduced-oxygen MAP gas composition attenuated the inhibition rates of E. coli O157:H7 and TV. L. monocytogenes continued to decline by an additional 0.6logCFU/g in post-treatment cold storage for 24h. Additionally, both rigid and flexible conventional plastic packages appear to be suitable for the in-package decontamination of lettuce with DACP. PMID- 27562349 TI - Change of Optical Intensity during Healing Process of Corneal Wound on Anterior Segment Optical Coherence Tomography. AB - The purpose of this study is to investigate the process of corneal wound healing after penetrating injury with the change in optical intensity on anterior segment optical coherence tomography (AS-OCT) and to investigate factors associated with severity of corneal scar. Forty-seven eyes from 47 patients with repaired corneal laceration were included. AS-OCT was performed on 1day, 1week, 1, 3 and 6 months after primary repair. Internal aberrations of wound edges were observed on AS-OCT images. Parameters including height of steps, width of gaps, maximal corneal thickness, area and optical intensity of corneal wound/scar were measured. The relationship between the parameters at day 1 and the optical intensity at 6 months were analyzed. The results showed that optical intensity of corneal wound/scar increased from 124.1 +/- 18.8 on day 1 postoperatively to 129.3 +/- 18.7, 134.2 +/- 23.4, 139.7 +/- 26.5, 148.2 +/- 26.4 at 1 week, 1 month, 3 months and 6 months postoperatively. Height of steps at 1 day after surgery was the only factor identified as correlated with optical intensity of corneal scar at 6 months (beta = 0.34, p = 0.024). The increase of optical intensity represents the process of fibrosis of corneal wound healing. Higher step after suturing is associated with more severity of corneal scar at last. PMID- 27562350 TI - Only married heterosexual Indian couples will be allowed to use surrogate mothers under proposed new law. PMID- 27562351 TI - Cultural differentiation does not entail group-level structure: The case for geographically explicit analysis. AB - Richerson et al. argue that relatively large cultural F ST values provide evidence for group structure and therefore scope for group selection. However, recent research on spatial patterns of cultural variation demonstrates that, as in the genetic case, apparent group structure can be a consequence of geographic clines, not group barriers. Such a pattern limits the scope for cultural group selection. PMID- 27562352 TI - Daily consumption of tea catechins improves aerobic capacity in healthy male adults: a randomized double-blind, placebo-controlled, crossover trial. AB - Our previous studies demonstrated that dietary supplementation with tea catechins combined with exercise improved endurance capacity in mice. This study aimed to demonstrate the effect of daily tea catechin consumption on aerobic capacity in humans. Sixteen Japanese non-athlete male subjects (aged 25-47 years) took 500 mL of a test beverage with or without tea catechins (570 mg) daily for 8 weeks and attended a training program twice a week. Aerobic capacity was evaluated by indirect calorimetry and near-infrared spectroscopy during graded cycle exercise. Catechin beverage consumption was associated with a significantly higher ventilation threshold during exercise and a higher recovery rate of oxygenated hemoglobin and myoglobin levels after graded cycle exercise when compared to subjects receiving the placebo beverage. These results indicate that daily consumption of tea catechins increases aerobic capacity when combined with semiweekly light exercise, which may be due to increased skeletal muscle aerobic capacity. PMID- 27562353 TI - Second-Generation Tunable pH-Sensitive Phosphoramidate-Based Linkers for Controlled Release. AB - We developed a second generation of tunable pH-sensitive linkers based on our phosphoramidate scaffold to release amine-containing drugs under acidic conditions. The pH-triggered phosphoramidate-based linkers are responsive to pH and do not require intracellular enzymatic action to initiate drug release. On the basis of the model scaffolds examined, phosphoramidate-based linkers were selected for particular properties for controlled release applications such as amine type, stability under physiological conditions, or release rates at various pH values such as intracellular endosomal conditions. Key to the pH-triggered amine release from these linker is a proximal carboxylic acid to promote hydrolysis of the phosphoramidate P-N bond, presumably through an intramolecular general acid-type mechanism. Phosphoramidate hydrolysis is largely governed by the pKa of the leaving amine. However, the proximity of the neighboring carboxylic acid attenuates the stability of the P-N bond to hydrolysis, thus allowing for control over the release of an amine from the phosphoramidate center. In addition, we observed that the Thorpe-Ingold effect and rigidification of the scaffold could further enhance the rate of release. Esterification of the neighboring carboxylic acid was found to protect the scaffold from rapid release at low pH. This latter observation is particularly noteworthy as it suggests that the phosphoramidate-based drug-conjugate scaffold can be protected as an ester prodrug for oral administration. While the tunability phosphoramidate linkers is attractive for applications in intracellular trafficking studies in which pH changes can trigger release of turn-on dyes, antibody drug conjugates, small molecule drug conjugates, and drug eluting stents (DES), the promise of oral delivery of drug conjugates is expected to have broad impact in controlled release applications. PMID- 27562354 TI - Biological markets explain human ultrasociality. AB - The evidence Gowdy & Krall (G&K) provide is more consistent with a biological markets explanation of human ultrasociality than a group selection explanation. Specifically, large-scale societies provide a better biological market for cooperation than do small-scale societies, allowing individuals to increase their fitness. Importantly, many of the quality-of-life costs G&K discuss (e.g., patriarchy) are not fitness costs. PMID- 27562355 TI - Systematic review with meta-analysis: prevalent vs. incident oesophageal adenocarcinoma and high-grade dysplasia in Barrett's oesophagus. AB - BACKGROUND: The proportion of oesophageal adenocarcinoma that is detected concurrently with initial Barrett's oesophagus diagnosis is not well studied. AIM: To compare the proportion of prevalent adenocarcinoma vs. incident adenocarcinoma found during surveillance of Barrett's. METHODS: We performed a systematic search of MEDLINE, EMBASE and Web of Science (from their inception to 31 May 2015) for cohort studies in adults with Barrett's (nondysplastic Barrett's +/- Barrett's with low-grade dysplasia) with minimum average follow-up of 3 years, and providing numbers of prevalent adenocarcinoma detected (concurrently with Barrett's diagnosis and up to 1 year afterwards) vs. incident adenocarcinoma detected (greater than 1 year after Barrett's diagnosis). Pooled weighted proportions of prevalent and incident adenocarcinoma were calculated, using a random effects model. RESULTS: On meta-analysis of 13 studies reporting on 603 adenocarcinomas in 9657 Barrett's patients, 85.1% of adenocarcinomas were classified as prevalent [95% confidence interval (CI), 78.1-90.2%) and 14.9% as incident (95% CI, 9.8-21.9%), with substantial heterogeneity (I(2) = 66%). Among nine studies reporting on 787 high-grade dysplasia and oesophageal adenocarcinomas in 8098 Barrett's patients, the proportion of prevalent high grade dysplasia-oesophageal adenocarcinoma was similar at 80.5% (95% CI, 68.1 88.8%, I(2) = 87%). These results remained stable across multiple subgroup analyses including study quality, setting, duration of follow-up and presence of baseline dysplasia. CONCLUSIONS: In our meta-analysis, four of five patients diagnosed with adenocarcinoma or high-grade dysplasia at index endoscopy or within 1 year of Barrett's follow-up were considered to be prevalent cases. Continued efforts are needed to identify patients with Barrett's before the development of adenocarcinoma. PMID- 27562356 TI - Scientific intuitions about the mind are wrong, misled by consciousness. AB - Logic is a fundamental reason why computational accounts of the mind have failed. Combinatorial complexity preventing computational accounts is equivalent to the Godelian incompleteness of logic. The mind is not logical, but only logical states and processes in the mind are accessible to subjective consciousness. For this reason, intuitions of psychologists, cognitive scientists, and mathematicians modeling the mind are biased toward logic. This is also true about the changes proposed in After Phrenology (Anderson 2014). PMID- 27562357 TI - The insulin-like growth factor system is modulated by exercise in breast cancer survivors: a systematic review and meta-analysis. AB - BACKGROUND: Insulin-like growth factors (IGF's) play a crucial role in controlling cancer cell proliferation, differentiation and apoptosis. Exercise has been postulated as an effective intervention in improving cancer-related outcomes and survival, although its effects on IGF's are not well understood. This meta-analysis aimed to determine the effects of exercise in modulating IGF's system in breast cancer survivors. METHODS: Databases of PuMed, EMBASE, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, SPORTDiscus, LILACS and Scopus were systematically searched up to November 2014. Effect estimates were calculated through a random-effects model of meta-analysis according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I (2) test. Risk of bias and methodological quality were evaluated using the PEDro score. RESULTS: Five randomized controlled trials (n = 235) were included. Most women were post-menopausal. High-quality and low risk of bias were found (mean PEDro score = 6.2 +/- 1). Exercise resulted in significant improvements on IGF-I, IGF-II, IGFBP-I, IGFBP-3, Insulin and Insulin resistance (P < 0.05). Non significant differences were found for Glucose. Aerobic exercise improved IGF-I, IGFBP-3 and Insulin. No evidence of publication bias was detected by Egger's test (p = 0.12). CONCLUSIONS: Exercise improved IGF's in breast cancer survivors. These findings provide novel insight regarding the molecular effects of exercise on tumoral microenvironment, apoptosis and survival in breast cancer survivors. PMID- 27562358 TI - Development of computerized masticatory force measurement system. AB - PURPOSE: The aim of this study was to assess the Maximum Voluntary Bite Force (MVBF) in Indian population with normal occlusion and after treatment of mandibular angle fracture. MATERIALS AND METHODS: This paper discusses the development of a sensor fork with modified load cell and computer-based bite force measuring system that generates force profile on the computer. This is a powerful diagnostic tool in response to the needs of dentists seeking an accurate way to dynamically measure occlusion. RESULTS: This study was carried out to evaluate the maximum voluntary bite force generated by the patients after the treatment of mandibular angle fracture. The in vivo measurements were repeated on the following day, week and two months later. The measurements of the device were highly repeatable. CONCLUSION: This development provides the cost effective and handy equipment for bite force measurement further, if again sensor thickness reduced, we will be able to get more close results of forces that are exactly generated during the mastication process. Our study shows a significant difference in mean bite force efficiency between the all the treatment weeks and increased with time at alpha = 0.05 level. The gender difference was statistically significant in the male and female. PMID- 27562359 TI - 3D Porous Graphene by Low-Temperature Plasma Welding for Bone Implants. AB - 3D scaffolds of graphene, possessing ultra-low density, macroporous microstructure, and high yield strength and stiffness can be developed by a novel plasma welding process. The bonding between adjacent graphene sheets is investigated by molecular dynamics simulations. The high degree of biocompatibility along with high porosity and good mechanical properties makes graphene an ideal material for use as body implants. PMID- 27562360 TI - Perspectives on the methods of a large systematic mapping of maternal health interventions. AB - BACKGROUND: Mapping studies describe a broad body of literature, and differ from classical systematic reviews, which assess more narrowly-defined questions and evaluate the quality of the studies included in the review. While the steps involved in mapping studies have been described previously, a detailed qualitative account of the methodology could inform the design of future mapping studies. OBJECTIVES: Describe the perspectives of a large research team on the methods used and collaborative experiences in a study that mapped the literature published on maternal health interventions in low- and middle-income countries (2292 full text articles included, after screening 35,048 titles and abstracts in duplicate). METHODS: Fifteen members of the mapping team, drawn from eight countries, provided their experiences and perspectives of the study in response to a list of questions and probes. The responses were collated and analysed thematically following a grounded theory approach. RESULTS: The objectives of the mapping evolved over time, posing difficulties in ensuring a uniform understanding of the purpose of the mapping among the team members. Ambiguity of some study variables and modifications in data extraction codes were the main threats to the quality of data extraction. The desire for obtaining detailed information on a few topics needed to be weighed against the benefits of collecting more superficial data on a wider range of topics. Team members acquired skills in systematic review methodology and software, and a broad knowledge of maternal health literature. Participation in analysis and dissemination was lower than during the screening of articles for eligibility and data coding. Though all respondents believed the workload involved was high, study outputs were viewed as novel and important contributions to evidence. Overall, most believed there was a favourable balance between the amount of work done and the project's outputs. CONCLUSIONS: A large mapping of literature is feasible with a committed team aiming to build their research capacity, and with a limited, simplified set of data extraction codes. In the team's view, the balance between the time spent on the review, and the outputs and skills acquired was favourable. Assessments of the value of a mapping need, however, to take into account the limitations inherent in such exercises, especially the exclusion of grey literature and of assessments of the quality of the studies identified. PMID- 27562361 TI - Cardiovascular Benefits of Wearing Particulate-Filtering Respirators: A Randomized Crossover Trial. AB - BACKGROUND: Practical approaches to protect individuals from ambient particulate matter (PM) are urgently needed in developing countries. Evidence on the health benefits of wearing particulate-filtering respirators is limited. OBJECTIVES: We evaluated the short-term cardiovascular health effects of wearing respirators in China. METHODS: A randomized crossover trial was performed in 24 healthy young adults in Shanghai, China in 2014. The subjects were randomized into two groups and wore particulate-filtering respirators for 48 hr alternating with a 3-week washout interval. Heart rate variability (HRV) and ambulatory blood pressure (BP) were continuously monitored during the 2nd 24 hr in each intervention. Circulating biomarkers were measured at the end of each intervention. Linear mixed-effect models were applied to evaluate the effects of wearing respirators on health outcomes. RESULTS: During the intervention periods, the mean daily average concentration of PM with an aerodynamic diameter < 2.5 MUm (PM2.5) was 74.2 MUg/m3. Compared with the absence of respirators, wearing respirators was associated with a decrease of 2.7 mmHg [95% confidence interval (CI): 0.1, 5.2 mmHg] in systolic BP and increases of HRV parameters, including 12.5% (95% CI: 3.8%, 21.2%) in high frequency (HF) power, 10.9% (95% CI: 1.8%, 20.0%) in the root mean square of the successive differences, and 22.1% (95% CI: 3.6%, 40.7%) in the percentage of normal RR intervals with duration > 50 msec different from the previous normal RR interval (pNN50). The presence of respirators was also associated with a decrease of 7.8% (95% CI: 3.5%, 12.1%) in the ratio of low frequency (LF)/HF power. CONCLUSIONS: Short-term wearing of particulate-filtering respirators may produce cardiovascular benefits by improving autonomic nervous function and reducing BP. Citation: Shi J, Lin Z, Chen R, Wang C, Yang C, Cai J, Lin J, Xu X, Ross JA, Zhao Z, Kan H. 2017. Cardiovascular benefits of wearing particulate-filtering respirators: a randomized crossover trial. Environ Health Perspect 125:175-180; http://dx.doi.org/10.1289/EHP73. PMID- 27562363 TI - Centering Transgender Voices in Research as a Fundamental Strategy Toward Expansion of Access to Care and Social Support. PMID- 27562362 TI - Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease. AB - Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage. We also found evidence that both complement and anti-M protein antibodies in serum from rM5-immunized rats have the potential to contribute to inflammation in heart valves by activating cardiac endothelium. More importantly, we have demonstrated by electrocardiography for the first time in the RAV model that elongation of P-R interval follows repetitive boost with rM5. Our observations provide experimental evidence for cardiac alterations following repeated exposure to GAS M protein with immunological and electrophysiological features resembling that seen in humans following recurrent GAS infection. PMID- 27562364 TI - Hearing Screening and Prevention of Hearing Loss in Adolescents. PMID- 27562365 TI - The Changing Landscape of Adolescent Marijuana Use Risk. PMID- 27562366 TI - Reaction-induced rheological weakening enables oceanic plate subduction. AB - Earth is the only terrestrial planet in our solar system where an oceanic plate subducts beneath an overriding plate. Although the initiation of plate subduction requires extremely weak boundaries between strong plates, the way in which oceanic mantle rheologically weakens remains unknown. Here we show that shear enhanced hydration reactions contribute to the generation and maintenance of weak mantle shear zones at mid-lithospheric depths. High-pressure friction experiments on peridotite gouge reveal that in the presence of hydrothermal water, increasing strain and reactions lead to an order-of-magnitude reduction in strength. The rate of deformation is controlled by pressure-solution-accommodated frictional sliding on weak hydrous phyllosilicate (talc), providing a mechanism for the 'cutoff' of the high peak strength at the brittle-plastic transition. Our findings suggest that infiltration of seawater into transform faults with long lengths and low slip rates is an important controlling factor on the initiation of plate tectonics on terrestrial planets. PMID- 27562367 TI - Shewanella inventionis sp. nov., isolated from deep-sea sediment. AB - A novel Gram-stain-negative, rod-shaped bacterial strain, designated KX27T, was isolated from deep-sea sediment of the Okinawa Trough and characterized on the basis of a polyphasic taxonomic approach. The phenotypic features of strain KX27T were similar to those of members of the genus Shewanella. Strain KX27T exhibited highest 16S rRNA gene sequence similarity (98.37 %) to Shewanellabasaltis JCM 14937T. Levels of gyrB gene sequence similarity between strain KX27T and its closest genetic neighbours were lower than 90 %, the species cut-off value for Shewanella. The DNA-DNA hybridization value between strain KX27T and S. basaltis JCM 14937T (54 %) was lower than the accepted species threshold. The predominant cellular fatty acids of strain KX27T were summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), C17 : 1omega8c, summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and iso-C15 : 0. The major polar lipids of strain KX27T were phosphatidylethanolamine and phosphatidylglycerol. On the basis of combined phenotypic, chemotaxonomic and phylogenetic analysis, strain KX27T represents a novel species of the genus Shewanella, for which the name Shewanella inventionis sp. nov. is proposed. The type strain is KX27T (=KCTC 42807T=CGMCC 1.15339T). PMID- 27562368 TI - Health research participants' preferences for receiving research results. AB - BACKGROUND: Participants in health research studies typically express interest in receiving the results from the studies in which they participate. However, participants' preferences and experiences related to receiving the results are not well understood. In general, the existing studies have had relatively small sample sizes and typically address specific and often sensitive issues within targeted populations. METHODS: This study used an online survey to explore attitudes and experiences of registrants in ResearchMatch, a large database of past, present, and potential health research participants. Survey respondents provided information related to whether or not they received research results from studies in which they participated, the methods used to communicate the results, their satisfaction with the results, and when and how they would like to receive research results from future studies. In all, 70,699 ResearchMatch registrants were notified of the study's topic. Of the 5207 registrants who requested full information about the study, 3381 respondents completed the survey. RESULTS: Approximately 33% of respondents with previous health research participation reported receiving the results. Approximately half of respondents with previous research participation reported no opportunity to request the results. However, almost all respondents said researchers should always or sometimes offer the results to participants. Respondents expressed particular interest in the results related to their (or a loved one's) health, as well as information about studies' purposes and any medical advances based on the results. In general, respondents' most preferred dissemination methods for the results were email and website postings. The least desirable dissemination methods for the results included Twitter, conference calls, and text messages. Across all the results, we compare the responses of respondents with and without previous research participation experience and those who have worked in research organizations versus those who have not. Compared to respondents who have previous participation experience, a greater proportion of respondents with no participation experience indicated that the results should always be shared with participants. Likewise, respondents with no participation experience placed higher importance on the receipt of each type of results' information included in the survey. CONCLUSION: We present findings from a survey assessing attitudes and experiences of a broad sample of respondents that addresses gaps in knowledge related to participants' preferences for receiving the results. The study's findings highlight the potential for inconsistency between respondents' expressed preferences to receive specific types of results via specific methods and researchers' unwillingness or inability to provide them. We present specific recommendations to shift the approach of new studies to investigate participants' preferences for receiving research results. PMID- 27562369 TI - Risk of MERS importation and onward transmission: a systematic review and analysis of cases reported to WHO. AB - BACKGROUND: The continuing circulation of MERS in the Middle East makes the international dissemination of the disease a permanent threat. To inform risk assessment, we investigated the spatiotemporal pattern of MERS global dissemination and looked for factors explaining the heterogeneity observed in transmission events following importation. METHODS: We reviewed imported MERS cases worldwide up to July 2015. We modelled importations in time based on air travel combined with incidence in Middle East. We used the detailed history of MERS case management after importation (time to hospitalization and isolation, number of hospitals visited,...) in logistic regression to identify risk factors for secondary transmission. We assessed changes in time to hospitalization and isolation in relation to collective and public health attention to the epidemic, measured by three indicators (Google Trends, ProMED-mail, Disease Outbreak News). RESULTS: Modelled importation events were found to reproduce both the temporal and geographical structure of those observed - the Pearson correlation coefficient between predicted and observed monthly time series was large (r = 0.78, p < 10(-4)). The risk of secondary transmission following importation increased with the time to case isolation or death (OR = 1.7 p = 0.04) and more precisely with the duration of hospitalization (OR = 1.7, p = 0.02). The average daily number of secondary cases was 0.02 [0.0,0.12] in the community and 0.20 [0.03,9.0] in the hospital. Time from hospitalisation to isolation decreased in periods of high public health attention (2.33 +/- 0.34 vs. 6.44 +/- 0.97 days during baseline attention). CONCLUSIONS: Countries at risk of importation should focus their resources on strict infection control measures for the management of potential cases in healthcare settings and on prompt MERS cases identification. Individual and collective awareness are key to substantially improve such preparedness. PMID- 27562370 TI - Site-specific Isopeptide Bridge Tethering of Chimeric gp41 N-terminal Heptad Repeat Helical Trimers for the Treatment of HIV-1 Infection. AB - Peptides derived from the N-terminal heptad repeat (NHR) of HIV-1 gp41 can be potent inhibitors against viral entry when presented in a nonaggregating trimeric coiled-coil conformation via the introduction of exogenous trimerization motifs and intermolecular disulfide bonds. We recently discovered that crosslinking isopeptide bridges within the de novo helical trimers added exceptional resistance to unfolding. Herein, we attempted to optimize (CCIZN17)3, a representative disulfide bond-stabilized chimeric NHR-trimer, by incorporating site-specific interhelical isopeptide bonds as the redox-sensitive disulfide surrogate. In this process, we systematically examined the effect of isopeptide bond position and molecular sizes of auxiliary trimeric coiled-coil motif and NHR fragments on the antiviral potency of these NHR-trimers. Pleasingly, (IZ14N24N)3 possessed promising inhibitory activity against HIV-1 infection and markedly increased proteolytic stability relative to its disulfide-tethered counterpart, suggesting good potential for further development as an effective antiviral agent for treatment of HIV-1 infection. PMID- 27562371 TI - Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human. AB - The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with alpha-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target. PMID- 27562374 TI - Controlling the Placement of Spherical Nanoparticles in Electrically Driven Polymer Jets and its Application to Li-Ion Battery Anodes. AB - Employing circumferentially uniform air flow through the sheath layer of the concentric coaxial nozzle, the gas-assisted electrospinning (GAES) utilizes both high electric field and controlled air flow to produce nanofibers. The ability to tailor the distribution of various nanofillers (1.85-12.92 vol% of spherical SiO2 and Si nanoparticles) in a polyvinyl alcohol jet is demonstrated by varying airflow rates in GAES. The distribution of nanofillers is measured from transmission electron microscopy and is analyzed using an image processing technique to perform the dispersion area analysis and obtain the most probable separation between nanoparticles using fast Fourier transform (FFT). The analysis in this study indicates an additional 350% improvement in dispersion area with the application of high but controlled airflow, and a 75 percent decrease in separation between nanoparticles from the FFT. The experiments in this study are in good agreement with a coarse-grained MD simulation prediction for a polymer nanocomposite system subjected to extensional deformation. Lastly, utilizing the sheath layer air flow in production of Li-battery anode material, a 680 mAh g-1 improvement is observed in capacity for nanofibers spun via GAES compared to ES at the same Si NP loading, which is associated with better dispersion of the electrochemically active nanoparticles. PMID- 27562372 TI - Psychological factors are important to return to pre-injury sport activity after anterior cruciate ligament reconstruction: expect and motivate to satisfy. AB - PURPOSE: To describe individuals' expectations, motivation, and satisfaction before, during, and after rehabilitation for ACL reconstruction and to explore how these factors were associated with return to pre-injury sport activity at 1 year follow-up. METHODS: Sixty-five individuals (34 males), median age 22 (15-45) years, scheduled for ACL reconstruction participated. Participants completed the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) and questions about expectations, satisfaction, and motivation pre-operatively and at 16 and 52 weeks after surgery. RESULTS: Prior to surgery, 86 % of participants stated that their goal was to return to their pre-injury sport activity. Those who had returned to their pre-injury sport activity at 52 weeks were more motivated during rehabilitation to return to their pre-injury activity level, more satisfied with their activity level and knee function at 52 weeks, and scored significantly higher on the IKDC-SKF [median 92.0 (range 66.7-100.0)] at 52 weeks, compared to those who had not returned [median 77.6 (range 50.6-97.7)]. CONCLUSION: Prior to ACL reconstruction, most participants expected to return to their pre-injury activity level. Higher motivation during rehabilitation was associated with returning to the pre-injury sport activity. The participants who had returned to their pre-injury sport activity were more satisfied with their activity level and knee function 1 year after the ACL reconstruction. Facilitating motivation might be important to support individuals in achieving their participation goals after ACL reconstruction. LEVEL OF EVIDENCE: Prospective cohort study, Level II. PMID- 27562373 TI - Preoperative CT planning of screw length in arthroscopic Latarjet. AB - PURPOSE: The Latarjet procedure has shown its efficiency for the treatment of anterior shoulder dislocation. The success of this technique depends on the correct positioning and fusion of the bone block. The length of the screws that fix the bone block can be a problem. They can increase the risk of non-union if too short or be the cause of nerve lesion or soft tissue discomfort if too long. Suprascapular nerve injuries have been reported during shoulder stabilisation surgery up to 6 % of the case. Bone block non-union depending on the series is found around 20 % of the cases. The purpose of this study was to evaluate the efficiency of this CT preoperative planning to predict optimal screws length. The clinical importance of this study lies in the observation that it is the first study to evaluate the efficiency of CT planning to predict screw length. METHODS: Inclusion criteria were patients with chronic anterior instability of the shoulder with an ISIS superior to 4. Exclusion criteria were patients with multidirectional instability or any previous surgery on this shoulder. Thirty patients were included prospectively, 11 of them went threw a CT planning, before their arthroscopic Latarjet. Optimal length of both screws was calculated, adding the size of the coracoid at 5 and 15 mm from the tip to the glenoid. Thirty-two mm screws were used for patients without planning. On a post-operative CT scan with 3D reconstruction, the distance between the screw tip and the posterior cortex was measured. A one-sample Wilcoxon test was used to compare the distance from the tip of the screw to an acceptable positioning of +/-2 mm from the posterior cortex. RESULTS: In the group without planning, screw 1 tended to differ from the acceptable positioning: mean 3.44 mm +/- 3.13, med 2.9 mm, q1; q3 [0.6; 4.75] p = 0.1118, and screw 2 differed significantly from the acceptable position: mean 4.83 mm +/- 4.11, med 3.7 mm, q1; q3 [1.7; 5.45] p = 0.0045. In the group with planning, position of screw 1 or 2 showed no significant difference from the acceptable position: mean 2.45 mm +/- 2.07 med 1.8 mm, q1; q3 [1; 3.3] p = 1; mean 2.75 mm +/- 2.32 med 2.3 mm, q1; q3 [1.25; 3.8] p = 0.5631. CONCLUSION: Unplanned Latarjet can lead to inaccurate screw length especially in the lower screw and can increase the risk of non-union and nerve damage. The clinical relevance of this article is that CT planning of screw length before surgery showed good results on post-operative CT. PMID- 27562375 TI - Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice. AB - BACKGROUND: Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium enriched rice) with a high resistant starch content (SRRS). RESULTS: Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-kappaB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-kappaB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. CONCLUSION: These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. (c) 2016 Society of Chemical Industry. PMID- 27562376 TI - Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction. AB - The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the NOP/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal, and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin, and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125, or 0.5 mg/infusion) both under a fixed ratio 1 and a progressive ratio schedule of reinforcement compared with wild-type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 MUg/infusion) and ethanol (10% v/v) self-administration, they showed significantly lower drug intake compared with Wt. Conversely, saccharin self administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction. PMID- 27562377 TI - Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H MRS and pCASL study. AB - The neurobiology of schizophrenia (SZ) may be altered in older versus younger adults with SZ, as less frequent episodes of symptom exacerbation and increased sensitivity to medications are observed in older age. The goal of this study was to examine the effect of age and diagnosis on glutamate and cerebral blood flow (rCBF) in adults with SZ and healthy controls. Young and older adults with SZ and healthy controls were recruited to participate in this study. Participants completed a neuropsychological battery and neuroimaging that included optimized magnetic resonance spectroscopy to measure anterior cingulate (AC) glutamate (Glu) and glutamine (Gln) and arterial spin labeling evaluation for rCBF. Regression analyses revealed significant effects of age with Glu, Gln, Gln/Glu, and AC white matter (WM) rCBF. Glu and WM rCBF decreased linearly with age while Gln and Gln/Glu increased linearly with age. Glu was lower in adults with SZ compared with healthy controls and in older adults versus younger adults but there was no interaction. Glu and WM rCBF were correlated with the UCSD Performance-Based Skills Assessment (UPSA) and processing speed, and the correlations were stronger in the SZ group. In the largest sample to date, lower Glu and elevated Gln/Glu levels were observed in adults with SZ and in older subjects. Contrary to expectation, these results do not show evidence of accelerated Glu aging in the anterior cingulate region in SZ compared with healthy controls. PMID- 27562378 TI - Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss. AB - The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies. PMID- 27562379 TI - Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection. AB - Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura. PMID- 27562380 TI - In vivo dissolution of levothyroxine soft gel capsules. PMID- 27562381 TI - Drastic anthocyanin increase in response to PAP1 overexpression in fls1 knockout mutant confers enhanced osmotic stress tolerance in Arabidopsis thaliana. AB - KEY MESSAGE : pap1 - D/fls1ko double mutant plants that produce substantial amounts of anthocyanin show tolerance to abiotic stress. Anthocyanins are flavonoids that are abundant in various plants and have beneficial effects on both plants and humans. Many genes in flavonoid biosynthetic pathways have been identified, including those in the MYB-bHLH-WD40 (MBW) complex. The MYB gene Production of Anthocyanin Pigment 1 (PAP1) plays a particularly important role in anthocyanin accumulation. PAP1 expression in many plant systems strongly increases anthocyanin levels, resulting in a dark purple color in many plant organs. In this study, we generated double mutant plants that harbor fls1ko in the pap1-D background (i.e., pap1-D/fls1ko plants), to examine whether anthocyanins can be further enhanced by blocking flavonol biosynthesis under PAP1 overexpression. We also wanted to examine whether the increased anthocyanin levels contribute to defense against osmotic stresses. The pap1-D/fls1ko mutants accumulated higher anthocyanin levels than pap1-D plants in both control and sucrose-treated conditions. However, flavonoid biosynthesis genes were slightly down-regulated in the pap1-D/fls1ko seedlings as compared to their expression in pap1-D seedlings. We also report the performance of pap1-D/fls1ko seedlings in response to plant osmotic stresses. PMID- 27562383 TI - Editorial: A brief Food & Nutrition Research status update. PMID- 27562384 TI - Contralateral prophylactic mastectomy and its impact on quality of life. PMID- 27562385 TI - Nuclear Dynamics and Electronic Effects of Hydrogen on Solid Surfaces. AB - Hydrogen is involved in a variety of chemical processes on surfaces. While hydrogen exhibits vibrational and rotational dynamics in its adsorption state, it in some cases undergoes diffusion into the substrate as well as on the surface, and participates in chemical reactions. Furthermore, hydrogen exchanges an electron with surfaces having a significant effect on the surface electronic structure. In this personal account, we review our recent studies on surface nuclear dynamics of hydrogen, hydrogen transport across surfaces, catalytic hydrogenation/isotope exchange reactions, and charge transfer between the surface and hydrogen by using a depth-resolved technique of nuclear reaction analysis and a quantum-state-selective detection of resonance enhanced multiphoton ionization in combination with surface science techniques. As a future prospect, we refer to ultraslow MU spin rotation spectroscopy for a direct probe of the hydrogen charge state at surfaces. PMID- 27562382 TI - Transcriptomic analysis reveals key early events of narciclasine signaling in Arabidopsis root apex. AB - KEY MESSAGE: Histochemical staining and RNA-seq data demonstrated that the ROS- and plant hormone-regulated stress responses are the key early events of narciclasine signaling in Arabidopsis root cells. Narciclasine, an amaryllidaceae alkaloid isolated from Narcissus tazetta bulbs, employs a broad range of functions on plant development and growth. However, its molecular interactions that modulate these roles in plants are not fully understood. To elucidate the global responses of Arabidopsis roots to short-term narciclasine exposure, we first measured the accumulation of H2O2 and O2- with histochemical staining, and then profiled the gene expression pattern in Arabidopsis root tips treated with 0.5 uM narciclasine across different exposure times by RNA-seq. Physiological measurements showed a significant increase in H2O2 began at 30-60 min of narciclasine treatment and O2- accumulated by 120 min. Compared with controls, 236 genes were upregulated and 54 genes were downregulated with 2 h of narciclasine treatment, while 968 genes were upregulated and 835 genes were downregulated with 12 h of treatment. The Gene Ontology analysis revealed that the differentially expressed genes were highly enriched during oxidative stress, including those involved in the "regulation of transcription", "response to oxidative stress", "plant-pathogen interaction", "ribonucleotide binding", "plant cell wall organization", and "ribosome biogenesis". Moreover, Kyoto Encyclopedia of Genes and Genomes pathway enrichment statistics suggested that carbohydrate metabolism, amino acid metabolism, amino sugar and nucleotide sugar metabolism, and biosynthesis of phenylpropanoid and secondary metabolites were significantly inhibited by 12 h of narciclasine exposure. Hence, our results demonstrate that hormones and H2O2 are important regulators of narciclasine signaling and help to uncover the factors involved in the molecular interplay between narciclasine and phytohormones in Arabidopsis root cells. PMID- 27562386 TI - The Psychological Consequences of Pre-Emigration Trauma and Post-Migration Stress in Refugees and Immigrants from Africa. AB - Over 50 million people have been displaced, some as a result of conflict, which exposure can lead to psychiatric sequelae. The aims of this study were to provide estimates of pre-emigration trauma, post-migration stress, and psychological sequelae of immigrants and refugees from predominantly Sub-Saharan Africa who immigrated to Sweden. We also examined the predictors of the psychiatric sequelae as well as acculturation within the host country. A total of 420 refugees and immigrants were enrolled using stratified quota sampling. A battery of questionnaires including the Harvard Trauma Questionnaire, Post-Migration Living Difficulties Scale, the Cultural Lifestyle Questionnaire; and the Hopkins Checklist were administered. Descriptive statistics, Chi square analyses, Pearson correlations, analysis of variance, and logistic and linear regression were performed to test the aims of the study. Eighty-nine percent of participants reported at least one traumatic experience prior to emigration. Forty-seven percent of refugees reported clinically significant PTSD and 20 % reported clinically significant depressive symptoms. Males reported a significantly greater number of traumatic events [F(1, 198) = 14.5, p < 0.001] and post migration stress than females [F(1, 414) = 5.3, p = 0.02], particularly on the financial, discrimination, and healthcare subscales. Females reported a higher prevalence of depressive symptoms when compared to males [F(1, 419) = 3.9, p = 0.05]. Those with a shorter duration in Sweden reported higher rates of PTSD [F(63, 419) = 1.7, p < 0.001]. The greater number of traumatic events was found to be significantly associated with the severity of PTSD symptoms [F(34, 419) = 9.6, p < 0.001]. Using regression analysis, 82 and 83 % of the variances associated with anxiety and depression, respectively, was explained by gender, education, religion, PTSD and post-migration stress. Sixty-nine percent of the variance associated with PTSD included education, number of traumatic events, depressive symptoms and post-migration stress. Forty-seven percent of the variance for acculturation was accounted for by a model that included age, education, duration in Sweden, anxiety, depression, and post-migration stress. These predictors were also significant for employment status with the exception of depressive symptoms. Multidimensional interventions that provide treatments to improve psychiatric symptoms in combination with advocacy and support to reduce stress (e.g., financial, access to health care) are recommended. The focus of the intervention may also be modified based on the gender of the participants. PMID- 27562387 TI - GLUT-1 Expression in Proliferative Endometrium, Endometrial Hyperplasia, Endometrial Adenocarcinoma and the Relationship Between GLUT-1 Expression and Prognostic Parameters in Endometrial Adenocarcinoma. AB - OBJECTIVE: Malignant cells show increased glucose uptake in in vitro and in vivo studies. This uptake is mediated by glucose transporter proteins. GLUT-1 is the most common transporter protein, and its expression is reported to be increase in many human cancers. The aim of this study is to determine the GLUT-1 overexpression in benign, hyperplastic, and malignant endometrial tissues, to evaluate the usefulness of GLUT-1 expression in endometrial hyperplasia, and to determine its role in the neoplastic progression to endometrioid type adenocarcinoma. We also aimed to analyze prognostic clinical parameters, predict prognosis, and survival. MATERIAL AND METHOD: We examined immunohistochemical expression of GLUT-1 in 91 cases of endometrial hyperplasia, 100 cases of endometrioid type adenocarcinoma, and 10 proliferative endometrial tissues. The percentage of positive cells and staining intensity were assessed in a semi quantitative fashion and scored (1+ to 3+). RESULTS: GLUT-1 immunoreactivity was not present in proliferative endometrium. Twenty-nine (31.9%) of 91 endometrial hyperplasia cases showed positive immunoreactivity, of which only six were cases of hyperplasia without atypia while 23 of them were cases with atypia. We found GLUT-1 positivity of 95% in endometrioid type adenocarcinoma. GLUT-1 overexpression was not significantly correlated with any of the clinicopathological parameters except histological grade in endometrioid adenocarcinoma; the survival was not found to be correlated with GLUT-1 expression. CONCLUSION: GLUT-1 immunostaining may be useful in distinguishing hyperplasia without atypia from hyperplasia with atypia; GLUT-1 overexpression is a consistent feature of endometrioid adenocarcinoma. A correlation between GLUT 1 expression and tumor grade has been found, although other prognostic parameters and survival has no meaningful correlation. PMID- 27562388 TI - Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms. AB - OBJECTIVE: Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms. MATERIAL AND METHOD: In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay. RESULTS: Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p < 0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T > C (rs3746444) polymorphisms and circulating tumor cell positivity were observed. CONCLUSION: The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size. PMID- 27562389 TI - Expression of Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Wilms Tumor. AB - OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) and Kidney injury molecule-1 (KIM-1) play important roles in both immunity and cell proliferation. It was reported previously that they are overexpressed in various human cancers. The present study was undertaken to examine the expressions of NGAL and KIM-1 in Wilms Tumors. MATERIAL AND METHOD: Tissue samples of 50 Wilms Tumors were evaluated and underwent immunhistochemical staining for NGAL and KIM-1 protein expressions. The correlations between them, and some clinical prognostic factors such as tumor weight, stage and histological features were also evaluated. RESULTS: Twenty-three (46%) of the cases were male while 27 (54%) were female. The mean age was found to be 3.26+/-2 years. The average tumor size was 9.16 +/- 2.9 cm in diameter and the average weight of the kidney was 478+/-312 gr. Thirteen (26%) cases were stage I, 18 (36%) cases were stage II, 7 (14%) cases were stage III, and 6 (12%) cases were stage IV. Thirty-nine cases were alive (78%), while 11 cases (22%) were deceased. Mean overall survival time was 68.2+/ 39.5 (2-148) months. NGAL expression was negative in all tumors except the neutrophils within the tumors. KIM-1 expression was positive in 37 tumors (74%), while it was absent in 13 tumors (26%). Using Mann-Whitney U Analysis, KIM-1 expression was found to be associated with the stage of the tumor (p=0.027). CONCLUSION: The preliminary data indicates that KIM-1 expression may be associated with stage in Wilms Tumor. However, further studies are needed to validate these pilot observations and to clarify the functional and mechanistic significance of this relevance. PMID- 27562390 TI - Comparison of Microvessel Density with Prognostic Factors in Invasive Ductal Carcinomas of the Breast. AB - OBJECTIVE: Angiogenesis plays a key role in tumor growth and metastasis. Determination of microvessel density is the most common technique used to evaluate the amount of the intratumoral angiogenesis in breast cancer. We have aimed to investigate the relationship with tumor angiogenesis and prognostic parameters in breast invasive ductal carcinomas. MATERIAL AND METHOD: In this study, a total of 100 invasive ductal carcinoma patients, who were diagnosed at the Department of Pathology, Ataturk University Faculty of Medicine between the years 2003-2008, were re-evaluated. Patient characteristics and clinicopathological findings were obtained from archival records. In the present study, microvessel density was determined by immunohistochemical staining by using anti-CD34 monoclonal antibody in the paraffin blocks. First, the most vascular area was selected in the tumor under a low magnification (40x) by a light microscope and then microvessels were counted under a higher magnification (200x). Patients were classified as low and high microvessel density depending on their microvessel counts. Chi-square test and multivariate linear regression analysis were used for statistical analysis (p<=0.05). RESULTS: We have determined that microvessel density increases as tumor size increases (p=0.001). Microvessel density was higher in patients with at least 10 lymph node metastases compared to those with no metastasis (p=0.05). However, there was no statistically significant difference between microvessel density and other prognostic factors such as histological grade, nuclear grade, patient age, vascular invasion, estrogen, progesterone receptor status, HER2/neu expression. CONCLUSION: In our study, we have found that microvessel density is associated with tumor size and lymph node metastasis in patients with invasive ductal carcinoma. PMID- 27562391 TI - A Six Sigma Trial For Reduction of Error Rates in Pathology Laboratory. AB - OBJECTIVE: A major target of quality assurance is the minimization of error rates in order to enhance patient safety. Six Sigma is a method targeting zero error (3.4 errors per million events) used in industry. The five main principles of Six Sigma are defining, measuring, analysis, improvement and control. Using this methodology, the causes of errors can be examined and process improvement strategies can be identified. The aim of our study was to evaluate the utility of Six Sigma methodology in error reduction in our pathology laboratory. MATERIAL AND METHOD: The errors encountered between April 2014 and April 2015 were recorded by the pathology personnel. Error follow-up forms were examined by the quality control supervisor, administrative supervisor and the head of the department. Using Six Sigma methodology, the rate of errors was measured monthly and the distribution of errors at the preanalytic, analytic and postanalytical phases was analysed. Improvement strategies were reclaimed in the monthly intradepartmental meetings and the control of the units with high error rates was provided. RESULTS: Fifty-six (52.4%) of 107 recorded errors in total were at the pre-analytic phase. Forty-five errors (42%) were recorded as analytical and 6 errors (5.6%) as post-analytical. Two of the 45 errors were major irrevocable errors. The error rate was 6.8 per million in the first half of the year and 1.3 per million in the second half, decreasing by 79.77%. CONCLUSION: The Six Sigma trial in our pathology laboratory provided the reduction of the error rates mainly in the pre-analytic and analytic phases. PMID- 27562392 TI - Comparison Between HER2, Estrogen Receptors and Progesterone Receptors in Primary Breast Carcinomas and Matched Lymph Node Metastases. AB - OBJECTIVE: In the current work, we compared HER2 by fluorescence in situ hybridization and estrogen and progesterone receptors by immunohistochemistry in matched primary breast carcinomas and their lymph node metastases. MATERIAL AND METHOD: Thirty-nine cases of primary and lymph node metastases were assessed for HER2. Primary tumors of the cases selected were known to be HER2 negative. Also, immunohistochemistry for estrogen and progesterone receptors was performed on 36 cases from the same cohort to assess any discrepancy between the primary tumor and the lymph node metastases. RESULTS: Out of 39 cases, one case was HER2 amplified in lymph node metastasis compared to non-amplified primary tumor. Approximately eight percent of cases (3/36) were estrogen receptor-negative in LN metastasis and 5.55% (2/36) were less strongly positive compared to the positive primary tumors. Nineteen percent (7/36) were progesterone receptor-negative in lymph node metastasis in contrast to the matched positive primary tumors, and 5.55% (2/36) were progesterone receptor-positive in lymph node as compared to their corresponding negative primary tumors. CONCLUSION: While most matched primary breast tumors and lymph node metastases show concordance in HER2, estrogen and progesterone receptor status, we confirmed the multiple reports that identified discordant results in a subset of cases. These results support the newly adopted guidelines that require testing for HER2 on metastatic lesions. PMID- 27562393 TI - Management and Outcome of Uveal Melanoma in a Single Tertiary Cancer Center in Jordan. AB - OBJECTIVE: The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an example of a referral tertiary cancer center in the Middle East. MATERIAL AND METHOD: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality. RESULTS: There was slight female preference, and the median age at diagnosis was 45 years. Eighteen (39%) eyes were treated by primary enucleation, and 28 (61%) eyes were treated by I-125 radioactive plaque. The melanoma was in the choroid in 40 (87%) eyes and in the ciliary body in 6 (13%) eyes, with no single tumor in the iris. According to the 7th edition of the American Joint Committee on Cancer staging system (UICC/AJCC); 8 (17%) were T1, 17 (36%) were T2, 16 (35%) were T3, and 5 (11%) were T4. One (2%) patient showed lymph node metastasis (N1), and 6 (13%) patients showed distant metastasis (M1). Pathologically, 2 (10%) of the enucleated eyes were spindle cell type, 4 (20%) were epithelioid cell type, and 14 (70%) were mixed type. Extrascleral extension was seen in three (15%) eyes, and optic nerve invasion in two (10%) eyes. After brachytherapy, 26 (93%) eyes were salvaged, and 2 eyes were consecutively enucleated; one for tumor recurrence, and one for uncontrolled painful neovascular glaucoma. The eye salvage rate post plaque was 93% (26/28), and the visual acuity for the salvaged eyes was equal or better than 0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than 0.1 in 10 (38%) eyes. CONCLUSION: The incidence of uveal melanomas in our region is low compared to that in the West with a younger age at presentation. Candidate tumors for radioactive plaque therapy were successfully controlled in 93% of cases. PMID- 27562394 TI - Nasal Polyp - An Incidental Paraganglioma. AB - The nose is an uncommon site for head and neck paraganglioma. The diagnosis is seldom established pre-operatively; its rarity, infrequent functionality and often benign biologic outcome underlie this fact. We present one such case in a 60-year-old man who presented with right nasal obstruction and episodic epistaxis. Rhinoscopy revealed a fleshy polypoid mass arising from the anterior cartilaginous nasal septum. Imaging studies excluded extra-nasal extension. The tumor was highly vascular showing numerous variable sized, mostly thin walled branching blood vessels akin to stag-horn shape simulating a vascular neoplasm. There were large areas of hyalinization. The typical tumor morphology was discernible only in focal areas. Immuno-histochemistry confirmed the diagnosis. The tumor cells expressed neuron specific enolase; S-100 stain demonstrated a vague zell-ballen pattern. Paraganglioma is a rare histologic diagnosis in nasal polypectomy specimen. We discuss the approach to exclude its morphologic mimics including vascular tumors. PMID- 27562395 TI - Adrenocortical Oncocytic Carcinoma: A Case Report and Review of the Histopathologic Diagnostic Criteria. AB - Oncocytic tumors are rare in the adrenal gland. The histopathological diagnosis of adrenocortical carcinoma is difficult due to the lack of precise diagnostic criteria for malignancy. A 44-year-old man was admitted to our hospital with left flank pain. Radiologically an adrenal mass was detected. After the excision and histopathologic evaluation of the mass, a diagnosis of adrenocortical oncocytic carcinoma was made. At least one of the features of more than 5 mitoses in 50 high power fields, atypical mitotic figures or venous invasion is required for the diagnosis of malignancy in adrenocortical tumors. It has been suggested that tumors that have more than one of the minor criteria of large size ( > 10 cm or > 200 gr), necrosis, capsular or sinusoidal invasion, should be evaluated as having uncertain malignant potential. PMID- 27562396 TI - Skeletal muscle ATP synthesis and cellular H(+) handling measured by localized (31)P-MRS during exercise and recovery. AB - (31)P magnetic resonance spectroscopy (MRS) is widely used for non-invasive investigation of muscle metabolism dynamics. This study aims to extend knowledge on parameters derived from these measurements in detail and comprehensiveness: proton (H(+)) efflux, buffer capacity and the contributions of glycolytic (L) and oxidative (Q) rates to ATP synthesis were calculated from the evolutions of phosphocreatine (PCr) and pH. Data are reported for two muscles in the human calf, for each subject and over a wide range of exercise intensities. 22 subjects performed plantar flexions in a 7T MR-scanner, leading to PCr changes ranging from barely noticeable to almost complete depletion, depending on exercise protocol and muscle studied by localized MRS. Cytosolic buffer capacity was quantified for the first time non-invasively and individually, as was proton efflux evolution in early recovery. Acidification started once PCr depletion reached 60-75%. Initial and end-exercise L correlated with end-exercise levels of PCr and approximately linear with pH. Q calculated directly from PCr and pH derivatives was plausible, requiring fewer assumptions than the commonly used ADP model. In conclusion, the evolution of parameters describing cellular energy metabolism was measured over a wide range of exercise intensities, revealing a relatively complete picture of muscle metabolism. PMID- 27562397 TI - Progesterone Response Element Variation in the OXTR Promoter Region and Paternal Care in New World Monkeys. AB - Paternal care is a complex social behavior common in primate species with socially monogamous mating systems and twin births. Evolutionary causes and consequences of such behavior are not well understood, nor are their neuroendocrine and genetic bases. However, the neuropeptide oxytocin (OXT) and its receptor (OXTR) are associated with parental care in mammalian lineages. Here we investigated the interspecific variation in the number of progesterone response elements (PREs) in the OXTR promoter region of 32 primate species, correlating genetic data with behavior, social systems, and ecological/life history parameters, while controlling for phylogeny. We verified that PREs are only present in New World monkeys and that PRE number is significantly correlated with the presence of paternal care in this branch. We suggest that PRE number could be an essential part of the genetic repertoire that allowed the emergence of taxon-specific complex social behaviors, such as paternal care in marmosets and tamarins. PMID- 27562399 TI - Novel Strategies to Discover Effective Drug Targets in Metabolic and Immune Therapy for Glioblastoma. AB - Glioblastoma multiforme is a common primary brain tumor, which exhibits an imbalance between glioma cell growth and glucose metabolism. Recent discoveries have found that the multiple pathways and downstream genes involved in the dysregulated metabolic pathway allow tumor to manifest and progress, which is critical to patients with glioblastoma associated with significant systemic and immunosuppression. Moreover, immune microenvironment is considered a major obstacle to generating an effective antitumor immune response. Therefore, identification of patient-specific tumor antigens through highly personalized approach, and effective combination with other therapeutic modalities such as molecular agents targeting tumor metabolic oncogene addiction and potent host immune modulators, may provide targets for more effective therapeutic strategies for glioblastoma. In this review, we aim to highlight the most recent findings regarding glucose uptake and proliferation, cell mobility and to expand our investigations and more comprehensively examine different aspects of glucose metabolism in glioblastoma, such as pentose phosphate pathway (PPP) and its enzymes, metabolic modulation of genetics and epigenetics and key metabolic regulators, importantly, tumor cell-induced glucose deprivation inhibits T-cell glycolysis and immunogenic functions. Furthermore, this review will concentrate on how to discover effective drug targets to regulate glucose metabolism in tumor and T cell growth for future glioblastoma therapies, and the challenges faced by the field of metabolism in tumor immune microenviroment. PMID- 27562398 TI - Subgroup differences in the associations between dog exposure during the first year of life and early life allergic outcomes. AB - BACKGROUND: The effect of dog exposure on the risk of children developing allergic disease remains controversial. Many analyses have not considered that associations may vary within population subgroups. OBJECTIVE: To examine whether associations between living with a dog in the first year of life and allergic outcomes vary within subgroups selected a priori (race, gender and delivery mode). METHODS: Black (n = 496) and White (n = 196) children enrolled in the WHEALS birth cohort study had a clinical examination at age 2 years to assess eczema and allergen-specific IgE (sIgE) and perform skin prick testing (SPT). Whether the child lived with an indoor dog in the first year of life was assessed through interview, as was doctor diagnosis of asthma at ages 3-6 years. RESULTS: Living with a dog was associated with decreased odds of having >= 1 positive SPT (OR = 0.56, 95% CI: 0.34, 0.91) and having eczema (OR = 0.34, 95% CI: 0.20, 0.60). The association with SPT was stronger in those children born via caesarean section (c-section) vs. vaginally (OR = 0.29, 95% CI: 0.12, 0.74 vs. OR = 0.76, 95% CI: 0.43, 1.37, respectively, interaction P = 0.087) and in those who were firstborn vs. not (OR = 0.27, 95% CI: 0.11, 0.67 vs. OR = 0.82, 95% CI: 0.45, 1.47, respectively, interaction P = 0.044). The association with eczema was stronger in children born vaginally compared with those born via caesarean section (OR = 0.17, 95% CI: 0.06, 0.43 vs. OR = 0.65, 95% CI: 0.31, 1.35, respectively, interaction P = 0.025) and was stronger in Black vs. White children (OR = 0.30, 95% CI: 0.15, 0.61 vs. OR = 0.78, 95% CI: 0.29, 2.11, respectively, interaction P = 0.12). Dog keeping was not significantly inversely associated with having >= 1 elevated sIgE and only approached statistical significance with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Results likely vary between studies due to variability of specific exposure-outcome associations in subgroups defined by other factors as well as the relative distributions of those subgroups. Important allergic disorder associations will be missed without subgroup analyses. PMID- 27562400 TI - Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI. AB - OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy). PMID- 27562401 TI - Impact of proton pump inhibitor treatment on pancreatic beta-cell area and beta cell proliferation in humans. AB - INTRODUCTION: Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS: Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined. The group was subdivided into patients without diabetes (n = 27), pre-diabetic patients (n = 31) and patients with diabetes (n = 35). RESULTS: Fasting glucose and HbA1c levels were not different between patients with and without PPI therapy (P = 0.34 and P = 0.30 respectively). Beta-cell area was higher in patients without diabetes than in patients with pre-diabetes or diabetes (1.33 +/- 0.12%, 1.05 +/- 0.09% and 0.66 +/- 0.07% respectively; P < 0.0001). There was no difference in beta-cell area between patients with and without PPI treatment (1.05 +/- 0.08% vs 0.87 +/- 0.08%, respectively; P = 0.16). Beta-cell replication was rare and not different between patients with and without PPI therapy (P = 0.20). PPI treatment was not associated with increased duct-cell replication (P = 0.18), insulin expression in ducts (P = 0.28) or beta-cell size (P = 0.63). CONCLUSIONS: These results suggest that in adult humans, chronic PPI treatment does not enhance beta cell mass or beta-cell function to a relevant extent. PMID- 27562404 TI - The influence of age on positions of the conus medullaris, Tuffier's line, dural sac, and sacrococcygeal membrane in infants, children, adolescents, and young adults. AB - BACKGROUND: The purpose of this study was to analyze the distances between the conus medullaris and the Tuffier's line, and between the dural sac and the sacrococcygeal membrane (SCM) in the same pediatric population. METHODS: Spinal magnetic resonance images and simple X-ray images of 350 patients aged from 1 month to 20 years were reviewed. Positions of the conus medullaris, Tuffier's line, the dural sac, and the SCM were identified. Each position was recorded in relation to the corresponding vertebral body segments. The distances between the conus medullaris and Tuffier's line, and between the dural sac and the SCM, were measured and then assessed according to age using an analysis of variance and a linear regression analysis. RESULTS: The median levels of the conus medullaris and Tuffier's line were in the lower third of L1 [the first lumbar vertebral body] and the middle third of L5, respectively. The levels of the conus medullaris and Tuffier's line were lower in younger populations. The distance between the conus medullaris and Tuffier's line ranged from 1.5 to 4.75 vertebral body height. However, a narrow range of 1.5-2.5 vertebral height was observed only in children younger than 2 years. The level of the dural sac did not differ greatly by age, but the upper limit of the SCM was lower in older populations. The distance between the dural sac and the upper limit of the SCM increased with age. CONCLUSIONS: In children, there is a distance of 1.5-4.75 vertebral body height between the conus medullaris and the Tuffier's line. However, these distances were narrower among younger populations. The distance between the dural sac and the upper limit of the SCM increased with age. PMID- 27562402 TI - Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome. AB - OBJECTIVE: McCune-Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. DESIGN: Retrospective cohort analysis. METHODS: Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height. RESULTS: Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 +/- 2.6 years (mean +/- 1 s.d.) (range: 0.5 10.9) and mean follow-up was 6.0 +/- 3.3 years (range: 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (DeltaBA/DeltaCA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P < 0.0001), and growth velocity Z-scores, which declined from 2.2 +/ 2.3 to -0.6 +/- 1.6 (P = 0.0004). Predicted adult height Z-scores increased significantly from -2.9 +/- 3.2 to -0.8 +/- 1.5 for subjects on treatment (P = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from -1.5 to 1.7 (median: -0.6), which were increased in comparison with untreated historical controls (P = 0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. CONCLUSIONS: In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height. PMID- 27562403 TI - Stress hormone release is a key component of the metabolic response to lipopolysaccharide: studies in hypopituitary and healthy subjects. AB - OBJECTIVE: Acute and chronic inflammatory and metabolic responses are generated by lipopolysaccharide (LPS) during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but whether these responses depend on intact pituitary release of hormones are not clearly identified. We compared the metabolic effects of LPS in hypopituitary patients (HPs) (in the absence of growth hormone (GH) and ACTH responses) and healthy control subjects (CTR) (with normal pituitary hormone responses). DESIGN: Single blind randomized. METHODS: We compared the effects of LPS on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic-euglycemic clamp conditions with muscle and fat biopsies in each period during infusion with saline or LPS. RESULTS: LPS increased cortisol and GH levels in CTR but not in HP. Also, it increased whole-body palmitate fluxes (3 fold) and decreased palmitate-specific activity (SA) 40-50% in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue (AT) mRNA was decreased in CTR. Although LPS increased phenylalanine fluxes significantly more in CTR, there was no difference in glucose metabolism between groups and intramyocellular insulin signaling was unaltered in both groups. CONCLUSIONS: LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared with HP and decreased adipocyte G0S2 mRNA only in CTR. Thus, in humans intact pituitary function and appropriate cortisol and GH release are crucial components of the metabolic response to LPS. PMID- 27562405 TI - Beta-amylase gene variability in introgressive wheat lines. AB - Variability of the beta-amylase gene in bread wheat, artificial amphidiploids, and derived introgression wheat lines was analyzed. Variation in homeologous beta amylase sequences caused by the presence of MITE (Miniature Inverted-Repeat Transposable Element) and its footprint has been identified in bread wheat. The previously unknown location of MITE in Triticum urartu and T. aestivum L. beta amylase gene has been found. These species have a MITE sequence in the third intron of beta-amylase, as opposed to Aegilops comosa and a number of other Triticeae species, which have it in the fourth intron. These two MITEs from Ae. comosa and T. aestivum were shown to have low identity scores. Miosa, an artificial amphidiploid, which has the M genome from Ae. comosa was shown to lose the MITE sequences. This loss might be caused by genomic shock due to allopolyploidization. PMID- 27562407 TI - Dalbavancin for the treatment of paediatric infectious diseases. AB - To review the topics of interest related to the use of dalbavancin in paediatric patients. PubMed was used to search for all of the studies published over the last 15 years using the key word "dalbavancin". A total of 36 manuscripts were selected, and due to the limited pediatric experience a further research was performed in order to identify clinical trials ongoing. Three studies that concerned children were found in clinicaltrials.gov. This review considers also the manuscripts published on the adult population in order to highlight the gaps requiring further research at pediatric age. Dalbavancin has emerged as a promising agent against resistant Gram-positive invasive infections. It is approved in the United States and Europe for the treatment of adult patients with acute bacterial skin and skin structure infections (SSTIs). Compared to other available antibiotics that are active against multi-resistant bacteria, the advantages of dalbavancin include a lower potential for drug interactions and the possibility of fewer required doses due to a longer half-life. Pharmacokinetic characteristics of dalbavacin are attractive for its clinical impact, especially for children who may avoid prolonged hospitalization and central venous access. However, further studies are needed to establish its appropriate paediatric dosage before it can be licensed for use in newborns and children. For younger patients, at a time when infections due to multidrug-resistant Gram-positive pathogens are increasing, dosage, efficacy and safety data for dalbavancin are needed to ensure the highest antimicrobial efficacy while also minimizing the risk of adverse events. PMID- 27562406 TI - Typhoidal and non-typhoidal Salmonella infections in Africa. AB - Salmonella infections in humans can range from self-limiting gastroenteritis typically associated with non-typhoidal Salmonella (NTS) to typhoidal fever, which can be life-threatening. Salmonellosis causes considerable morbidity and mortality in both humans and animals, and has a significant socioeconomic impact worldwide. In Africa, it is difficult to evaluate the situation of salmonellosis due to the non-availability of facilities capable of performing the tests essential for the diagnosis of typhoidal and non-typhoidal Salmonella infections. This article reviews important work in the literature, including the epidemiology, disease burden, pathogenesis, genomics, diagnosis, treatment, emergence and tracking of multidrug-resistant (MDR) Salmonella infections and intercontinental transmission of Salmonella to Africa. Searches of PubMed and Google Scholar were completed and the retrieved list of relevant publications were further screened. The literature revealed that the most common form of the disease in Africa is gastroenteritis, with bacterial multiplication in intestinal submucosa and diarrhoea caused by the inflammatory response and, perhaps, also by toxins. In addition to the high burden of Salmonella infection in Africa, MDR Salmonella species is on the rise in the continent, which might pose difficulties in the treatment of the disease. PMID- 27562408 TI - What is the (p-) value of the P-value? PMID- 27562409 TI - Effect of lung-protective ventilation-induced respiratory acidosis on the duration of neuromuscular blockade by rocuronium. AB - PURPOSE: The purpose of this study was to elucidate whether lung-protective ventilation-induced respiratory acidosis increased the duration of neuromuscular blockade by rocuronium. METHODS: A total of 72 patients were enrolled. After the induction of general anesthesia, rocuronium 0.6 mg/kg real body weight was administered. Tidal volume and positive end-expiratory pressure were randomly assigned as either 10 ml/kg predicted body weight and 0 cmH2O (group S) or 6 ml/kg and 5 cmH2O (group L), respectively. Respiratory rate was started at 10/min. Neuromuscular blockade was monitored by acceleromyography at the adductor pollicis with train-of-four stimulation. The time from the initial bolus injection of rocuronium to first recovery of the first twitch was defined as DUR1. Immediately, rocuronium 0.15 mg/kg was administered. The time from first recovery of the first twitch to second recovery of the first twitch was defined as DUR2. We also measured arterial pH (pH1 and pH2, respectively). RESULTS: Data from 66 patients (33 each in groups L and S) were eventually available. pH1 and pH2 were significantly lower in group L compared with group S [pH1: 7.308 (7.288 7.334) vs. 7.439 (7.423-7.466); p < 0.01, pH2: 7.306 (7.285-7.330) vs. 7.453 (7.436-7.476); p < 0.01]. DUR1 and DUR2 were significantly prolonged in group L compared with group S [DUR1: 31 (24-36) vs. 24 (20-30) min; p = 0.029, DUR2: 19 (15-22) vs. 15 (12-17) min; p = 0.020]. CONCLUSIONS: Lung-protective ventilation induced respiratory acidosis increased the duration of neuromuscular blockade by rocuronium. PMID- 27562410 TI - Erratum to: Clinical characteristics and outcomes of HIV-seropositive men treated with surgery for prostate cancer. PMID- 27562411 TI - Many important language universals are not reducible to processing or cognition. AB - Christiansen & Chater (C&C) ignore the many linguistic universals that cannot be reduced to processing or cognitive constraints, some of which we present. Their claim that grammar is merely acquired language processing skill cannot account for such universals. Their claim that all other universal properties are historically and culturally based is a nonsequitur about language evolution, lacking data. PMID- 27562412 TI - What are kids vaping? Results from a national survey of US adolescents. AB - OBJECTIVE: To examine what substances US youth vape. METHODS: Data come from Monitoring the Future, an annual, nationally representative survey of USA 12th grade, 10th-grade and 8th-grade students. Respondents reported what substance they vaped the last time they used a vaporiser such as an e-cigarette. RESULTS: Among students who had ever used a vaporiser, 65-66% last used 'just flavouring' in 12th, in 10th and in 8th grade, more than all other responses combined. In all three grades, the percentage using 'just flavouring' was above 57% for males, females, African-Americans, Hispanics, Whites, and students both with and without a parent with a college degree. Nicotine use came in a distant second, at about 20% in 12th and 10th grade and 13% in 8th grade. Taking into account youth who vaped nicotine at last use increases national estimates of tobacco/nicotine prevalence in the past 30 days by 24-38% above and beyond cigarette smoking, which is substantial but far less than estimates that assume all vaporiser users inhale nicotine. CONCLUSIONS: These results challenge the common assumption that all vaporiser users inhale nicotine. They (a) call into question the designation of vaporisers and e-cigarettes as ENDS ('Electronic Nicotine Delivery System'), (b) suggest that the recent rise in adolescent vaporiser use does not necessarily indicate a nicotine epidemic, and (c) indicate that vaporiser users can be candidates for primary prevention programmes. Finally, the results suggest the importance of developing different rationales for the regulation of vaporiser devices as compared to the regulation of substances marketed for vaporiser use. PMID- 27562413 TI - A prospective study contrasting the psychiatric outcome in drug-resistant epilepsy between patients who underwent surgery and a control group. AB - OBJECTIVE: Psychiatric morbidity in drug-resistant epilepsy is frequent and has a negative influence on quality of life. Surgery is proven to be the best therapeutic alternative for treating seizures. However, it is inconclusive with the current evidence whether surgery, per se, is a risk factor or promotes amelioration of psychiatric disorders. Until now, most studies have been cross sectional with small or heterogeneous groups. In addition, the few prospective studies did not have an identical control group. The present study aims to clarify the role of surgery in psychopathologic alterations. METHODS: We analyzed, through a prospective case-control study, the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery and those who continued with pharmacologic treatment due to not being suitable for surgery. The assessments were performed during presurgical evaluation and 6 months after surgery. We studied psychiatric changes for each group, compared differences between groups, and also analyzed de novo and remission cases. Finally, we determined associated factors for postsurgical psychiatric disturbances. RESULTS: The surgical group experienced a significant decrease in psychopathologic alterations in comparison with the control group. In addition, distress perception of surgical patients also improved, whereas it did not decrease in the control group. Patients who underwent surgery presented a decrease in depressive and anxiety symptoms, whereas the nonsurgical group increased its anxiety levels. De novo disturbances that appeared after surgery were less frequent than in nonsurgical patients. We observed significant favorable outcomes considering de novo versus remission cases for anxiety, depression, and total symptoms only in the surgical group. The two main predictors for psychiatric disorders after surgery were presurgical psychiatric functioning and surgery. SIGNIFICANCE: Provides evidence that surgery improves psychiatric functioning in drug-resistant epilepsy through a prospective controlled study. PMID- 27562414 TI - Intergroup competition may not be needed for shaping group cooperation and cultural group selection. AB - Because intergroup interactions often are mixed-motive rather than strictly zero sum, groups often negotiate settlements that enable both cultures to thrive. Moreover, group prosperity rests on in-group love (rather than out-group hate) that emerges also absent intergroup competition or comparison. It follows that cultural group selection (CGS) reflects group effectiveness in organizing in group trust and cooperation, rather than winning (in)direct intergroup competitions. PMID- 27562415 TI - Online solid phase extraction with liquid chromatography-tandem mass spectrometry for determination of estrogens and glucocorticoids in water. AB - The present work describes the development of a novel fully automated online solid phase extraction (SPE) coupled with high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) using negative electrospray ionisation (ESI) for the simultaneous determination of six estrogens and six glucocorticoids in water. Filtered water samples (5mL) were preconcentrated on a HyperSepTM Retain PEP SPE cartridge, eluted in back-flush mode, and separated on an LC column before analysis by tandem mass spectrometry. The total analysis time for each sample was 17min. Different experimental parameters such as the type of online SPE cartridge, loading flow rate, and composition of methanol in the loading phase were optimised. The intra-day repeatability of method ranged from 1.48 to 9.68% for all analytes, and the inter-day reproducibility ranged from 2.03 to 8.63% for all analytes, except for dexamethasone at 11.95%. These were calculated based on the peak area responses of the targeted analytes spiked at 50ng/L in ultrapure water. The method also showed good linearity from 1 to 100ng/L, with the limits of detection (LODs) ranging from 0.16 to 2.14ng/L. The proposed method was applied to the analysis of municipal wastewater. This fully automated online SPE extraction coupled with LC-MS/MS method is effective and reliable to measure estrogens and glucocorticoids simultaneously due to its high throughput, relatively low solvent consumption, reusability of the online SPE cartridge, and reduction of manual labor. PMID- 27562416 TI - Fluorescent derivatization combined with aqueous solvent-based dispersive liquid liquid microextraction for determination of butyrobetaine, l-carnitine and acetyl l-carnitine in human plasma. AB - A novel aqueous solvent-based dispersive liquid-liquid microextraction (AS-DLLME) method was combined with narrow-bore liquid chromatography and fluorescence detection for the determination of hydrophilic compounds. A remover (non-polar solvent) and extractant (aqueous solution) were introduced into the derivatization system (acetonitrile) to obtain a water-in-oil emulsion state that increased the mass transfer of analytes. As a proof of concept, three quaternary ammonium substances, including butyrobetaine, l-carnitine and acetyl-l-carnitine, were also used as analytes and determined in pharmaceuticals, personal care products, food and human plasma. The analytes were derivatized with 4 bromomethylbiphenyl for fluorescence detection and improved retention in the column. The linear response was 10-2000nM for l-carnitine and acetyl-l-carnitine with a good determination coefficient (r(2)>0.998) in the standard solution. The detection limit for l-carnitine and acetyl-l-carnitine was 4.5 fmol. The method was also successfully applied to a 1MUL sample of human plasma. In the linearity calculations for determining butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma, the determination coefficients ranged from 0.996 to 0.999. Linear regression exhibited good reproducibility and a relative standard deviation better than 7.50% for the slope and 9.06% for the intercept. To characterize highly hydrophilic compounds in various samples, the proposed method provides good sensitivity for a small sample volume with a low consumption of toxic solvents. PMID- 27562417 TI - Imaging features of immunoglobulin G4-related disease. AB - Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that was first recognised as a systemic disease in 2003, when patients with autoimmune pancreatitis were found to have extrapancreatic manifestations. Since 2003, IgG4 RD has been described in a diverse range of other organs including the biliary tree, orbits, lacrimal glands, salivary glands, lungs, kidneys, aorta, retroperitoneum, lymph nodes, pachymeninges, prostate and pituitary gland. The disease frequently occurs in the absence of pancreatic involvement. The imaging manifestations of IgG4-RD are broad and variable depending on the organ involved. The majority of individual organ appearances are non-specific and differentiation between IgG4-RD and potentially more serious conditions is not usually possible based on radiological findings in one organ alone. However, if there are simultaneous findings typical of IgG4-RD in multiple organs then this is a key diagnostic clue and IgG4-RD should be considered as one of the main differentials. This review article examines the spectrum of imaging appearances of IgG4-RD. Increased awareness of the spectrum of radiological appearances of IgG4-RD throughout the body and subsequent consideration of the condition may potentially avoid invasive treatment and lead to more prompt corticosteroid therapy. PMID- 27562419 TI - The continuing evolution of ultrasocial economic organization. AB - Ultrasociality, as expressed in agricultural, monetary, and fossil fuel economies, has spurred exponential growth in population and in resource use that now threaten civilization. These threats take the form of prisoner's dilemmas. Avoiding collapse requires more cooperative economic organization that must be informed by knowledge of human behavior and cultural evolution. The evolution of a cooperative information economy is one possibility. PMID- 27562418 TI - Functional characterization of tissue factor in von Willebrand factor-dependent thrombus formation under whole blood flow conditions. AB - Von Willebrand factor (VWF) plays an important role in mediating platelet adhesion and aggregation under high shear rate conditions. Such platelet aggregates are strengthened by fibrin-network formation triggered by tissue factor (TF). However, little is known about the role of TF in VWF-dependent thrombus formation under blood flow conditions. We evaluated TF in thrombus formation on immobilized VWF under whole blood flow conditions in an in vitro perfusion chamber system. Surface-immobilized TF amplified intra-thrombus fibrin generation significantly under both low and high shear flow conditions, while TF in sample blood showed no appreciable effects. Furthermore, immobilized TF enhanced VWF-dependent platelet adhesion and aggregation significantly under high shear rates. Neutrophil cathepsin G and elastase increased significantly intra thrombus fibrin deposition on immobilized VWF-TF complex, suggesting the involvement of leukocyte inflammatory responses in VWF/TF-dependent mural thrombogenesis under these flow conditions. These results reveal a functional link between VWF and TF under whole blood flow conditions, in which surface immobilized TF and VWF mutually contribute to mural thrombus formation, which is essential for normal hemostasis. By contrast, TF circulating in blood may be involved in systemic hypercoagulability, as seen in sepsis caused by severe microbial infection, in which neutrophil inflammatory responses may be active. PMID- 27562420 TI - Association of inflammation with specific symptoms of depression in a general population of older people: The English Longitudinal Study of Ageing. AB - Elevated levels of inflammatory markers, such as C-reactive protein, are well documented in people with depression. Few studies have examined whether the association between inflammation and depression is symptom specific, and differs according to antidepressant treatment. Using data from the English Longitudinal Study of Ageing (N=5909), cross-sectional analyses revealed a significant dose response association between C-reactive protein and the symptoms of fatigue (P<0.001), restless sleep (P=0.03), low energy (P=0.02) and feeling depressed (P=0.04), but not other symptoms. These associations were absent in users of anti depressant medication. Our findings suggest the C-reactive protein-depression association is symptom-specific and modified by antidepressant treatment. PMID- 27562421 TI - Microglial production of TNF-alpha is a key element of sustained fear memory. AB - The proinflammatory cytokine productions in the brain are altered in a process of fear memory formation, indicating a possibility that altered microglial function may contribute to fear memory formation. We aimed to investigate whether and how microglial function contributes to fear memory formation. Expression levels of M1 and M2-type microglial marker molecules in microglia isolated from each conditioned mice group were assessed by real-time PCR and immunohistochemistry. Levels of tumor necrosis factor (TNF)-alpha, but not of other proinflammatory cytokines produced by M1-type microglia, increased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Administration of inhibitors of TNF-alpha production facilitated extinction of fear memory. On the other hand, expression levels of M2-type microglia-specific cell adhesion molecules, CD206 and CD209, were decreased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Our findings indicate that microglial TNF-alpha is a key element of sustained fear memory and suggest that TNF-alpha inhibitors can be candidate molecules for mitigating posttraumatic reactions caused by persistent fear memory. PMID- 27562423 TI - Linguistic structure emerges through the interaction of memory constraints and communicative pressures. AB - If memory constraints were the only limitation on language processing, the best possible language would be one with only one word. But to explain the rich structure of language, we need to posit a second constraint: the pressure to communicate informatively. Many aspects of linguistic structure can be accounted for by appealing to equilibria that result from these two pressures. PMID- 27562422 TI - In vitro adherence of Lactobacillus strains isolated from the vaginas of healthy Iranian women. AB - BACKGROUND: The lactobacilli are a part of the bacterial flora of the human vagina. Detection of normal Lactobacillus species in the vaginas of healthy women in different geographical locations, and evaluation of their specific properties, can aid in the selection of the best species for preventing sexually transmitted diseases in the future. This study was performed to isolate and identify the Lactobacillus species in the vaginas of healthy women and to evaluate the adherence of these lactobacilli to Vero and HeLa cell lines. METHODS: The study included 100 women. Bacteria were isolated from healthy women and purified. Phenotypic and biochemical tests were performed to identify the lactobacilli. The Lactobacillus species were detected by molecular methods using polymerase chain reaction amplification of the full length of the 16S rDNA of the isolated bacteria. Several isolates of each species were then selected to study their adherence to Vero and HeLa cell lines. RESULTS: Among the 50 samples taken from healthy women meeting the inclusion criteria, Lactobacillus species were identified in 33 (66%) samples. Of these lactobacilli, 14 isolates were Lactobacillus crispatus, six (18.2%) were Lactobacillus gasseri, nine (27%) were Lactobacillus rhamnosus, and the rest were either Lactobacillus salivarius (6%) or Lactobacillus plantarum (6%). L. rhamnosus showed the greatest adhesion to the cells when compared to the other tested species. All the lactobacilli isolated in this study showed a smaller capacity for cell adherence when compared with control species. CONCLUSION: L. crispatus, L. rhamnosus, and L. gasseri were the dominant Lactobacillus species in the vaginas of healthy women in Iran. L. rhamnosus attached more readily to the cells than did the other species; therefore, this isolate is a good candidate for further studies on the potential health benefits and application of lactobacilli as probiotics. PMID- 27562424 TI - Expectation of nocebo hyperalgesia affects EEG alpha-activity. AB - Changes in EEG activity have been related to clinical and experimental pain. Expectation of a negative outcome can lead to pain enhancement (nocebo hyperalgesia) and can alter the response to therapeutic interventions. The present study characterizes EEG alteration related to pain facilitation by nocebo. Thirty healthy subjects were randomly assigned to the nocebo or control group. Five-minute EEG was recorded under: resting state, tonic innocuous heat and tonic noxious heat before and after the application of a sham inert cream to the non-dominant volar forearm combined with cognitive manipulation. The intensity and unpleasantness of heat-induced pain increased after cognitive manipulation in the nocebo group compared to control and was associated with enhanced low alpha (8-10Hz) activity. However, changes in alpha activity were predicted by catastrophizing but not by pain intensity or unpleasantness, which suggest that low alpha power might reflect brain activity related to negative cognitive-affective responses to pain. PMID- 27562426 TI - Mitochondrial haplogroups and expression studies of commonly used human cell lines. AB - We developed a multiplex fragment length analysis (MFLA) for clearly assigning mitochondrial haplogroups mostly endemic in Europe for future cardiac diagnostics. As a technical proof, 23 commonly used human cell lines were haplotyped as reference standards. The functional analysis on mtDNA copies per cell revealed no correlation to haplogroups but a relatively high rate of mitochondria per cell and at the same time a very low expression of all mitochondrial and some nuclear encoded mitochondrial related genes. Established MFLA is an easy to handle method for analysing European mitochondrial haplogroups to perform epidemic studies and elucidate correlations to distinct diseases. PMID- 27562425 TI - H,K-ATPase type 2 contributes to salt-sensitive hypertension induced by K(+) restriction. AB - In industrialized countries, a large part of the population is daily exposed to low K(+) intake, a situation correlated with the development of salt-sensitive hypertension. Among many processes, adaptation to K(+)-restriction involves the stimulation of H,K-ATPase type 2 (HKA2) in the kidney and colon and, in this study, we have investigated whether HKA2 also contributes to the determination of blood pressure (BP). By using wild-type (WT) and HKA2-null mice (HKA2 KO), we showed that after 4 days of K(+) restriction, WT remain normokalemic and normotensive (112 +/- 3 mmHg) whereas HKA2 KO mice exhibit hypokalemia and hypotension (104 +/- 2 mmHg). The decrease of BP in HKA2 KO is due to the absence of NaCl-cotransporter (NCC) stimulation, leading to renal loss of salt and decreased extracellular volume (by 20 %). These effects are likely related to the renal resistance to vasopressin observed in HKA2 KO that may be explained, in part by the increased production of prostaglandin E2 (PGE2). In WT, the stimulation of NCC induced by K(+)-restriction is responsible for the elevation in BP when salt intake increases, an effect blunted in HKA2-null mice. The presence of an activated HKA2 is therefore required to limit the decrease in plasma [K(+)] but also contributes to the development of salt-sensitive hypertension. PMID- 27562428 TI - Evaluation of a new community-based curriculum in disaster medicine for undergraduates. AB - BACKGROUND: Nowadays, many medical schools include training in disaster medicine in undergraduate studies. This study evaluated the efficacy of a disaster medicine curriculum recently designed for Saudi Arabian medical students. METHODS: Participants were 15 male and 14 female students in their fourth, fifth or sixth year at Jazan University Medical School, Saudi Arabia. The course was held at the Research Center in Emergency and Disaster Medicine and Computer Sciences Applied to the Medical Practice in Novara, Italy. RESULTS: The overall mean score on a test given before the course was 41.0 % and it increased to 67.7 % on the post-test (Wilcoxon test for paired samples: z = 4.71, p < 0.0001). There were no significant differences between the mean scores of males and females, or between students in their fourth, fifth or sixth year of medical school. CONCLUSIONS: These results show that this curriculum is effective for teaching disaster medicine to undergraduate medical students. Adoption of this course would help to increase the human resources available for dealing with disaster situations. PMID- 27562427 TI - Drop-out rate among patients treated with omalizumab for severe asthma: Literature review and real-life experience. AB - BACKGROUND: In patients with asthma, particularly severe asthma, poor adherence to inhaled drugs negatively affects the achievement of disease control. A better adherence rate is expected in the case of injected drugs, such as omalizumab, as they are administered only in a hospital setting. However, adherence to omalizumab has never been systematically investigated. The aim of this study was to review the omalizumab drop-out rate in randomized controlled trials (RCTs) and real-life studies. A comparative analysis was performed between published data and the Italian North East Omalizumab Network (NEONet) database. RESULTS: In RCTs the drop-out rate ranged from 7.1 to 19.4 %. Although the reasons for withdrawal were only occasionally reported, patient decision and adverse events were the most frequently reported causes. In real-life studies the drop-out rate ranged from 0 to 45.5 %. In most cases lack of efficacy was responsible for treatment discontinuation. According to NEONet data, 32 % of treated patients dropped out, with an increasing number of drop outs observed over time. Patient decision and lack of efficacy accounted for most treatment withdrawals. CONCLUSIONS: Treatment adherence is particularly crucial in patients with severe asthma considering the clinical impact of the disease and the cost of non-adherence. The risk of treatment discontinuation has to be carefully considered both in the experimental and real-life settings. Increased knowledge regarding the main reasons for patient withdrawal is important to improve adherence in clinical practice. PMID- 27562429 TI - Commentary: the role of epidemiologists in funding biomedical education and research. AB - Melissa Perry served as the president of the American College of Epidemiology from September 2014 to September 2015. This is a written version of her Presidential Address at the 2015 Annual Meeting. Her speech was inspired by a 2014 Wall Street Journal commentary by Dr. Ferric Fang of the Washington University School of Medicine and Dr. Arturo Casadevall of the Albert Einstein College of Medicine of Yeshiva University. They likened the process of submitting a research proposal to the National Institutes of Health to playing the Powerball lottery. In her speech, Dr. Perry argued for the urgent need for epidemiology researchers to reach out to policymakers and the public in support of our field to ensure the continuation of research projects that can help improve the health of citizens everywhere. PMID- 27562430 TI - The Enigmatic Cornea and Intraocular Lens Calculations: The LXXIII Edward Jackson Memorial Lecture. AB - PURPOSE: To review the progress and challenges in obtaining accurate corneal power measurements for intraocular lens (IOL) calculations. DESIGN: Personal perspective, review of literature, case presentations, and personal data. METHODS: Through literature review findings, case presentations, and data from the author's center, the types of corneal measurement errors that can occur in IOL calculation are categorized and described, along with discussion of future options to improve accuracy. RESULTS: Advances in IOL calculation technology and formulas have greatly increased the accuracy of IOL calculations. Recent reports suggest that over 90% of normal eyes implanted with IOLs may achieve accuracy to within 0.5 diopter (D) of the refractive target. Though errors in estimation of corneal power can cause IOL calculation errors in eyes with normal corneas, greater difficulties in measuring corneal power are encountered in eyes with diseased, scarred, and postsurgical corneas. For these corneas, problematic issues are quantifying anterior corneal power and measuring posterior corneal power and astigmatism. Results in these eyes are improving, but 2 examples illustrate current limitations: (1) spherical accuracy within 0.5 D is achieved in only 70% of eyes with post-refractive surgery corneas, and (2) astigmatism accuracy within 0.5 D is achieved in only 80% of eyes implanted with toric IOLs. CONCLUSION: Corneal power measurements are a major source of error in IOL calculations. New corneal imaging technology and IOL calculation formulas have improved outcomes and hold the promise of ongoing progress. PMID- 27562431 TI - Influence of Patient Age on Intraocular Lens Power Prediction Error. AB - PURPOSE: To examine whether intraocular lens (IOL) power prediction error (PE) after cataract surgery differs according to patient age. DESIGN: Prospective cohort study. METHODS: We consecutively enrolled 75 eyes of 75 patients 59 years of age or younger, and 150 eyes of 150 patients in each of 3 age groups (60-69, 70-79, and 80-89 years), for whom phacoemulsification and implantation of a single-piece acrylic IOL was planned. The IOL power was calculated using the optimized SRK/T formula. Objective refraction was measured using an autorefractometer at approximately 3 months postoperatively, and the mean arithmetic PE and median absolute PE were compared among age groups. RESULTS: The mean preoperative refractive error predicted by the SRK/T formula was similar among age groups (P = .4179). The mean postoperative spherical equivalent was significantly more myopic in younger patients (P < .0001). Mean PE was -0.24 diopters (D) in those <=59 years of age, -0.17 D in those 60-69 years of age, 0.11 D in those 70-79 years of age, and -0.05 D in those 80-89 years of age; the mean PE was less myopic in older patients (P = .0008). The median absolute PE did not differ significantly among groups (P = .6192). Mean PE was positively correlated with age (P < .0001). Multiple regression analysis revealed that age, preoperative axial length, average corneal curvature, and anterior chamber depth were independent predictors of the age-related difference in PE. CONCLUSION: PE was less myopic by approximately 0.06 D per decade as age increased, suggesting that patient age should be considered when selecting IOL power. PMID- 27562432 TI - Arabinogalactan protein motif-containing receptor-like kinases are likely to play the negative feedback factor to maintain proper root hair length. AB - Coordination of the events between cytoplasm and cell wall is necessary for the proper cellular activity of plants. Cell wall-associated receptor kinases are likely to play the interface for the extra-to-internal signaling process. Arabidopsis ROOT HAIR SPECIFIC 10 (RHS10), belonging to the proline-rich extensin like receptor kinase (PERK) family, is a Ser/Thr protein kinase with arabinogalactan protein (AGP) motifs in its extracellular domain (ECD). RHS10 and other angiosperm PERK homologs are inhibitory in root hair tip growth. The ECD deletion analysis of RHS10 indicates that proline residues, including AGP motifs, in the ECD are required for the root hair inhibition. The kinase domain of RHS10 physically interacts with an RNase (RNS2), and both RHS10 and RNS2 show the consistent genetic interaction in terms of root hair phenotype and root RNA levels. The root hair-inhibitory function of the cell wall-associated receptor kinase RHS10 may provide a negative feedback tool between cell wall and cytoplasm for the determination of proper length of the root hair. PMID- 27562433 TI - Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. AB - The CRISPR/Cas9 system provides a flexible approach for genome engineering of genetic loci. Here, we successfully achieved precise gene targeting in sheep by co-injecting one-cell-stage embryos with Cas9 mRNA and RNA guides targeting three genes (MSTN, ASIP, and BCO2). We carefully examined the sgRNAs:Cas9-mediated targeting effects in injected embryos, somatic tissues, as well as gonads via cloning and sequencing. The targeting efficiencies in these three genes were within the range of 27-33% in generated lambs, and that of simultaneously targeting the three genes was 5.6%, which demonstrated that micro-injection of zygotes is an efficient approach for generating gene-modified sheep. Interestingly, we observed that disruption of the MSTN gene resulted in the desired muscle hypertrophy that is characterized by enlarged myofibers, thereby providing the first detailed evidence supporting that gene modifications had occurred at both the genetic and morphological levels. In addition, prescreening for the off-target effect of sgRNAs was performed on fibroblasts before microinjection, to ensure that no detectable off-target mutations from founder animals existed. Our findings suggested that the CRISPR/Cas9 method can be exploited as a powerful tool for livestock improvement by simultaneously targeting multiple genes that are responsible for economically significant traits. PMID- 27562434 TI - Comparison of glycemic variability in Japanese patients with type 1 diabetes receiving insulin degludec versus insulin glargine using continuous glucose monitoring: A randomized, cross-over, pilot study. AB - AIMS: To compare glucose variability in patients with type 1 diabetes (T1D) treated with insulin glargine (IGla) versus insulin degludec (IDeg) using continuous glucose monitoring (CGM). METHODS: Thirteen patients with T1D were randomly assigned to receive IDeg once-daily followed by IGla twice-daily or vice versa. They were evaluated for glucose variability by CGM after >4weeks of treatment with either insulin, and then were crossed over to the other, and evaluated by CGM after >4weeks. RESULTS: The total daily insulin dose (TDD) (U/kg/day) and the total daily basal insulin dose (U/kg/day) in the patients were significantly lower while taking IDeg than while taking IGla (mean [95% confidence interval] 0.72 [0.61-0.83] vs. 0.76 [0.64-0.88]; P=0.001, 0.29 [0.22 0.36] vs. 0.33 [0.26-0.40]; P=0.001), although no significant difference was noted in the patients while on IDeg versus while on IGla in 24-h mean glucose and SDs of 24-h glucose. Again, the range of postprandial glucose increase was not significantly different between the meals in the patients while taking IDeg (P=0.288) but significantly different in the patients while taking IGla (P=0.033). CONCLUSIONS: The use of once-daily IDeg leads not only to similar glycemic control to that seen with twice-daily IGla even in those who received IGla prior to the study, but also to significant decreases in TDD and long-acting basal insulin dose. PMID- 27562435 TI - A RNA nanotechnology platform for a simultaneous two-in-one siRNA delivery and its application in synergistic RNAi therapy. AB - Incorporating multiple copies of two RNAi molecules into a single nanostructure in a precisely controlled manner can provide an efficient delivery tool to regulate multiple gene pathways in the relation of mutual dependence. Here, we show a RNA nanotechnology platform for a two-in-one RNAi delivery system to contain polymeric two RNAi molecules within the same RNA nanoparticles, without the aid of polyelectrolyte condensation reagents. As our RNA nanoparticles lead to the simultaneous silencing of two targeted mRNAs, of which biological functions are highly interdependent, combination therapy for multi-drug resistance cancer cells, which was studied as a specific application of our two in-one RNAi delivery system, demonstrates the efficient synergistic effects for cancer therapy. Therefore, this RNA nanoparticles approach has an efficient tool for a simultaneous co-delivery of RNAi molecules in the RNAi-based biomedical applications, and our current studies present an efficient strategy to overcome multi-drug resistance caused by malfunction of genes in chemotherapy. PMID- 27562437 TI - When is the spread of a cultural trait due to cultural group selection? The case of religious syncretism. AB - The reproduction of cultural systems in cases where cultural group selection may occur is typically incomplete, with only certain cultural traits being adopted by less successful cultural groups. Why a particular trait and not another is transmitted might not be explained by cultural group selection. We explore this issue through the case of religious syncretism. PMID- 27562436 TI - Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens. AB - BACKGROUND: Ocular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~50 % of presumed infectious uveitis cases. The objective of this study is to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis. METHODS: This is a proof-of-concept study, in which intraocular fluid samples were obtained from five subjects with known diagnoses, and one subject with bilateral chronic uveitis without a known etiology. Samples were subjected to MDS, and results were compared with those from conventional diagnostic tests. Pathogens were identified using a rapid computational pipeline to analyze the non-host sequences obtained from MDS. RESULTS: Unbiased MDS of intraocular fluid produced results concordant with known diagnoses in subjects with (n = 4) and without (n = 1) uveitis. Samples positive for Cryptococcus neoformans, Toxoplasma gondii, and herpes simplex virus 1 as tested by a Clinical Laboratory Improvement Amendments-certified laboratory were correctly identified with MDS. Rubella virus was identified in one case of chronic bilateral idiopathic uveitis. The subject's strain was most closely related to a German rubella virus strain isolated in 1992, one year before he developed a fever and rash while living in Germany. The pattern and the number of viral identified mutations present in the patient's strain were consistent with long-term viral replication in the eye. CONCLUSIONS: MDS can identify fungi, parasites, and DNA and RNA viruses in minute volumes of intraocular fluid samples. The identification of chronic intraocular rubella virus infection highlights the eye's role as a long-term pathogen reservoir, which has implications for virus eradication and emerging global epidemics. PMID- 27562438 TI - Left-handed polyproline-II helix revisited: proteins causing proteopathies. AB - Left-handed polyproline-II type helix is a regular conformation of polypeptide chain not only of fibrous, but also of folded and natively unfolded proteins and peptides. It is the only class of regular secondary structure substantially represented in non-fibrous proteins and peptides on a par with right-handed alpha helix and beta-structure. In this study, we have shown that polyproline-II helix is abundant in several peptides and proteins involved in proteopathies, the amyloid-beta peptides, protein tau and prion protein. Polyproline-II helices form two interaction sites in the amyloid-beta peptides, which are pivotal for pathogenesis of Alzheimer's disease (AD). It also with high probability is the structure of the majority of tau phosphorylation sites, important for tau hyperphosphorylation and formation of neurofibrillary tangles, a hallmark of AD. Polyproline-II helices form large parts of the structure of the folded domain of prion protein. They can undergo conversion to beta-structure as a result of relatively small change of one torsional angle of polypeptide chain. We hypothesize that in prions and amyloids, in general polyproline-II helices can serve as structural elements of the normal structure as well as dormant nuclei of structure conversion, and thus play important role in structure changes leading to the formation of fibrils. PMID- 27562439 TI - Outflow monitoring of a pneumatic ventricular assist device using external pressure sensors. AB - BACKGROUND: In this study, a new algorithm was developed for estimating the pump outflow of a pneumatic ventricular assist device (p-VAD). The pump outflow estimation algorithm was derived from the ideal gas equation and determined the change in blood-sac volume of a p-VAD using two external pressure sensors. OBJECTIVES: Based on in vitro experiments, the algorithm was revised to consider the effects of structural compliance caused by volume changes in an implanted unit, an air driveline, and the pressure difference between the sensors and the implanted unit. METHODS: In animal experiments, p-VADs were connected to the left ventricles and the descending aorta of three calves (70-100 kg). Their outflows were estimated using the new algorithm and compared to the results obtained using an ultrasonic blood flow meter (UBF) (TS-410, Transonic Systems Inc., Ithaca, NY, USA). RESULTS: The estimated and measured values had a Pearson's correlation coefficient of 0.864. The pressure sensors were installed at the external controller and connected to the air driveline on the same side as the external actuator, which made the sensors easy to manage. PMID- 27562440 TI - Effect of CO2 on Microbial Denitrification via Inhibiting Electron Transport and Consumption. AB - Increasing anthropogenic CO2 emissions have been reported to influence global biogeochemical processes; however, in the literature the effects of CO2 on denitrification have mainly been attributed to the changes it causes in environmental factors, while the direct effects of CO2 on denitrification remain unknown. In this study, increasing CO2 from 0 to 30 000 ppm under constant environmental conditions decreased total nitrogen removal efficiency from 97% to 54%, but increased N2O generation by 240 fold. A subsequent mechanistic study revealed that CO2 damaged the bacterial membrane and directly inhibited the transport and consumption of intracellular electrons by causing intracellular reactive nitrogen species (RNS) accumulation, suppressing the expression of key electron transfer proteins (flavoprotein, succinate dehydrogenase, and cytochrome c) and the synthesis and activity of key denitrifying enzymes. Further study indicated that the inhibitory effects of CO2 on the transport and consumption of electrons were caused by the decrease of intracellular iron due to key iron transporters (AfuA, FhuC, and FhuD) being down-regulated. Overall, this study suggests that the direct effect of CO2 on denitrifying microbes via inhibition of intracellular electron transport and consumption is an important reason for its negative influence on denitrification. PMID- 27562441 TI - Does ultrasociality really exist - and is it the best predictor of human economic behaviors? AB - We agree that human economic structures can be informed by comparative analyses; however, we do not agree with several of Gowdy & Krall's specific assertions, which may hinder the generative potential of their model. We discuss these limitations from both biological and economic perspectives, and offer an alternative explanation for the expression of human economic behaviors based on individual optimization strategies. PMID- 27562442 TI - Beyond disjoint brain networks: Overlapping networks for cognition and emotion. AB - It is taken for granted that the brain is composed of a set of networks. But what is a brain network? How should we characterize them? Adding to Anderson's (2014) persuasive anti-modular framework, I propose that (1) networks do not have a single, unique function; (2) networks are highly overlapping and not disjoint; and (3) tasks reconfigure networks found at rest. PMID- 27562443 TI - Deconstructing Pediatric Blenderized Tube Feeding: Getting Started and Problem Solving Common Concerns. AB - Blenderized tube feeding has been steadily gaining in popularity among parents and caregivers of tube-fed children. Numerous websites and social media accounts are devoted to the topic, and the parent may be the one to initially broach the subject of implementing this type of feeding plan. This article discusses several different approaches to planning a blenderized tube feeding. As practitioners build their knowledge of and familiarity with blenderized tube feeding, they may feel more comfortable recommending this method to a wider variety of patients. PMID- 27562444 TI - Hypophosphatemia in Enterally Fed Patients in the Surgical Intensive Care Unit. AB - INTRODUCTION: Hypophosphatemia has been associated with refeeding malnourished patients, but its clinical significance is unclear. We investigated the incidence of refeeding hypophosphatemia (RH) in the surgical intensive care unit (SICU) and its association with early enteral nutrition (EN) administration and clinical outcomes. METHODS: We performed a retrospective review of a 2-year database of patients receiving EN in the SICU. RH was defined as a post-EN phosphorus (PHOS) level decrement of >0.5 mg/dL to a nadir <2.0 mg/dL within 8 days from EN initiation. We investigated the risk factors for RH and examined its association with clinical outcomes using multivariable regression analyses. RESULTS: In total, 213 patients comprised our analytic cohort. Eighty-three of 213 (39%) individuals experienced RH and 43 of 130 (33%) of the remaining patients experienced non-RH hypophosphatemia (nadir PHOS level <2.0 mg/dL). Overall, there was a total 59% incidence of hypophosphatemia of any cause (N = 126). Nutrition parameters did not differ between groups; most patients were initiated on EN within 48 hours of SICU admission, and timing of EN initiation was not a significant predictor for the development of RH. The median hospital length of stay (LOS) was 21 and 24 days for those with and without RH, respectively ( P = .79); RH remained a nonsignificant predictor for hospital LOS in the multivariable analysis. CONCLUSIONS: RH is common in the SICU but is not related to timing or amount of EN. Hypophosphatemia is also common in the critically ill, but regardless of etiology, it was not found to be a predictor of worse clinical outcomes. PMID- 27562445 TI - Idelalisib in Waldenstrom macroglobulinemia: high incidence of hepatotoxicity. PMID- 27562446 TI - Flexible Ultrafast Aqueous Rechargeable Ni//Bi Battery Based on Highly Durable Single-Crystalline Bismuth Nanostructured Anode. AB - A new type of ultrafast Ni//Bi battery with high flexibility and impressive electrochemical performance is demonstrated for the first time based on an as prepared Bi electrode as the anode and a NiCo2 O4 nanowire electrode as the cathode. The NiCo2 O4 //Bi battery is able to deliver a remarkable energy density of 85.8 W h kg-1 at a power density of 1.02 kW kg-1 , and still retains 55.4 W h kg-1 when the power density is increased to 21.2 kW kg-1 . PMID- 27562447 TI - Conflicts of interest common among US cancer guideline authors, study finds. PMID- 27562448 TI - Young People's Sexual and Reproductive Health Interventions in Developing Countries: Making the Investments Count. PMID- 27562449 TI - Interventions to Prevent Child Marriage Among Young People in Low- and Middle Income Countries: A Systematic Review of the Published and Gray Literature. AB - Child marriage, defined as marriage before the age of 18 years, is a human rights violation that can have lasting adverse educational and economic impacts. The objective of this review was to identify high-quality interventions and evaluations to decease child marriage in low- and middle-income countries. PubMed, Embase, PsycInfo, CINAHL Plus, Popline, and the Cochrane Databases were searched without language limitations for articles published through November 2015. Gray literature was searched by hand. Reference tracing was used, as well as the unpacking of systematic reviews. Retained articles were those that were evaluated as having high-quality interventions and evaluations using standardized scoring. Eleven high-quality interventions and evaluations were abstracted. Six found positive results in decreasing the proportion married or increasing age at marriage, one had both positive and negative findings, and four had no statistical impact on the proportion married or age at marriage. There is wide range of high-quality, impactful interventions included in this review which can inform researchers, donors, and policy makers about where to make strategic investments to eradicate marriage, a current target of the Sustainable Development Goals. Despite the cultural factors that promote child marriage, the diversity of interventions can allow decision makers to tailor interventions to the cultural context of the target population. PMID- 27562450 TI - Interventions to Prevent Sexually Transmitted Infections, Including HIV, Among Young People in Low- and Middle-Income Countries: A Systematic Review of the Published and Gray Literature. AB - Sexually transmitted infections (STIs), including HIV, are prevalent among adolescents and can have lasting adverse health consequences. The objective of this review is to identify high-quality interventions and evaluations to decrease STI transmission and related risky behaviors among young people in low- and middle-income countries. PubMed, Embase, PsycInfo, Cinahl Plus, Popline, and the Cochrane Databases were searched without language limitations for articles published through November 2015. Gray literature was searched by hand. Reference tracing was utilized, as well as the unpacking of systematic reviews. Retained articles were those that were evaluated as having high-quality interventions and evaluations using standardized scoring. Twenty-one high-quality interventions and evaluations were abstracted. Three reported declines in STI diagnoses, three reported declines in STI symptoms, six showed declines in risky sexual behavior, seven reported increases in abstinence, 11 found increases in condom use, and five reported increases in health care utilization. There is a wide range of rigorously evaluated high-quality interventions included in this review that can inform researchers, donors, and policy makers about where to make strategic investments to decrease the spread of STIs, including HIV. With the recent advent of biomarkers, researchers can use a gold standard measure to assess intervention impact. The diversity of interventions can allow decision makers to tailor interventions to the context, age range, and gender of the target population. PMID- 27562451 TI - Detailed Methodology for Systematic Reviews of Interventions to Improve the Sexual and Reproductive Health of Young People in Low- and Middle-Income Countries. AB - The goal of this project was to systematically review and compile evidence on interventions in low- and middle-income countries, which targeted three adverse health-related outcomes for young people (ages 10-24): (1) early pregnancy and repeat pregnancy; (2) child marriage; and (3) sexually transmitted infections including human immunodeficiency virus. We searched the gray and published literature to identify interventions and developed a scoring system to assess whether these interventions and their evaluations were of high quality. The three review articles in this volume focus on behavioral outcomes and provide a summary of interventions and evaluations that were both successful and unsuccessful in their impact on the targeted outcomes. This commentary provides the details of the methodology that are common across all three review articles. PMID- 27562452 TI - Interventions to Prevent Unintended and Repeat Pregnancy Among Young People in Low- and Middle-Income Countries: A Systematic Review of the Published and Gray Literature. AB - Adolescent pregnancy, particularly unintended pregnancy, can have lasting social, economic, and health outcomes. The objective of this review is to identify high quality interventions and evaluations to decrease unintended and repeat pregnancy among young people in low- and middle-income countries. PubMed, Embase, PsycInfo, Cinahl Plus, Popline, and the Cochrane Databases were searched for all languages for articles published through November 2015. Gray literature was searched by hand. Reference tracing was utilized, as well as unpacking systematic reviews. Selected articles were those that were evaluated as having high-quality interventions and evaluations using standardized scoring. Twenty-one high-quality interventions and evaluations were abstracted. Nine reported statistically significant declines in pregnancy rates (five cash transfer programs, one education curriculum, two life-skills curricula, and a provision of contraception intervention), seven reported increases in contraceptive use (three provision of contraception interventions, two life-skills curricula, a peer education program, and a mass media campaign), two reported decreases in sexual activity (a cash transfer program and an education and life-skills curriculum), and two reported an increase in age of sexual debut (both cash transfer programs). The selected high quality, effective interventions included in this review can inform researchers, donors, and policy makers about where to make strategic investments to decrease unintended pregnancy during young adulthood. Additionally, this review can assist with avoiding investments in interventions that failed to produce significant impact on the intended outcomes. The diversity of successful high-quality interventions, implemented in a range of venues, with a diversity of young people, suggests that there are multiple strategies that can work to prevent unintended pregnancy. PMID- 27562454 TI - An in-house multilocus SNP genotyping assay for evaluation of complex genetic diseases. AB - BACKGROUND: With an increase in the discovery of newer genetic loci/polymorphisms in complex multifactorial diseases, there is also an increased need for methods that can simultaneously genotype multiple loci in a cost-effective manner. Using coronary artery disease (CAD) as a model, the study aimed to develop an in-house multilocus assay for simultaneous detection of 17 genetic variants in 11 genes implicated in CAD. METHODS: A multiplex polymerase chain reaction (PCR)-based reverse line blot hybridization (MPCR-RLBH) approach was used, where each DNA sample was amplified using two separate MPCRs, and the alleles were genotyped using covalently immobilized, amino-linked sequence-specific oligonucleotide probes using an enhanced chemiluminescence system. The assay performance was tested on 75 healthy controls and 75 angiographically proven CAD cases. Validation was done by automated Sanger sequencing. RESULTS: The assay could successfully discriminate both the alleles at CETP (I405V), LPL (D9N), NOS3 (T 786G and E298D), LIPC (C-514T), FGB (G-455A), ITGB3 (L33P), AGT (M235T), and MTR (A2756G) loci. Certain mutations included in this assay such as ins242G, ins397G, E387K, L393K in the LDLR; N291S in the LPL; D442G in the CETP; and T833C in the CBS genes were found to be absent. The genotype results obtained using this assay showed 100% concordance with sequencing. CONCLUSION: The study demonstrated development and validation of a multiplex SNP genotyping assay that can be used to assess genetic risk factors in CAD. The assay provides a cost-effective alternative to expensive high throughput genotyping systems in common molecular research laboratories. PMID- 27562453 TI - Cep295 is a conserved scaffold protein required for generation of a bona fide mother centriole. AB - Centrioles surrounded by pericentriolar material (PCM) serve as the core structure of the centrosome. A newly formed daughter centriole grows into a functional mother centriole. However, the underlying mechanisms remain poorly understood. Here we show that Cep295, an evolutionarily conserved protein, is required for generation of a bona fide mother centriole organizing a functional centrosome. We find that Cep295 is recruited to the proximal centriole wall in the early stages of procentriole assembly. Cep295 then acts as a scaffold for the proper assembly of the daughter centriole. We also find that Cep295 binds directly to and recruits Cep192 onto the daughter centriole wall, which presumably endows the function of the new mother centriole for PCM assembly, microtubule-organizing centre activity and the ability for centriole formation. These findings led us to propose that Cep295 acts upstream of the conserved pathway for centriole formation and promotes the daughter-to-mother centriole conversion. PMID- 27562455 TI - Quantitative analysis of diet structure by real-time PCR, reveals different feeding patterns by two dominant grasshopper species. AB - Studies on grasshopper diets have historically employed a range of methodologies, each with certain advantages and disadvantages. For example, some methodologies are qualitative instead of quantitative. Others require long experimental periods or examine population-level effects, only. In this study, we used real-time PCR to examine diets of individual grasshoppers. The method has the advantage of being both fast and quantitative. Using two grasshopper species, Oedaleus asiaticus and Dasyhippus barbipes, we designed ITS primer sequences for their three main host plants, Stipa krylovii, Leymus chinensis and Cleistogenes squarrosa and used real-time PCR method to test diet structure both qualitatively and quantitatively. The lowest detection efficiency of the three grass species was ~80% with a strong correlation between actual and PCR-measured food intake. We found that Oedaleus asiaticus maintained an unchanged diet structure across grasslands with different grass communities. By comparison, Dasyhippus barbipes changed its diet structure. These results revealed why O. asiaticus distribution is mainly confined to Stipa-dominated grassland, and D. barbipes is more widely distributed across Inner Mongolia. Overall, real-time PCR was shown to be a useful tool for investigating grasshopper diets, which in turn offers some insight into grasshopper distributions and improved pest management. PMID- 27562457 TI - Yolk-Shell MnO@ZnMn2 O4 /N-C Nanorods Derived from alpha-MnO2 /ZIF-8 as Anode Materials for Lithium Ion Batteries. AB - Manganese oxides (MnOx ) are promising anode materials for lithium ion batteries, but they generally exhibit mediocre performances due to intrinsic low ionic conductivity, high polarization, and poor stability. Herein, yolk-shell nanorods comprising of nitrogen-doped carbon (N-C) coating on manganese monoxide (MnO) coupled with zinc manganate (ZnMn2 O4 ) nanoparticles are manufactured via one step carbonization of alpha-MnO2 /ZIF-8 precursors. When evaluated as anodes for lithium ion batteries, MnO@ZnMn2 O4 /N-C exhibits an reversible capacity of 803 mAh g-1 at 50 mA g-1 after 100 cycles, excellent cyclability with a capacity of 595 mAh g-1 at 1000 mAg-1 after 200 cycles, as well as better rate capability compared with those non-N-C shelled manganese oxides (MnOx ). The outstanding electrochemical performance is attributed to the unique yolk-shell nanorod structure, the coating effect of N-C and nanoscale size. PMID- 27562456 TI - Functional evaluation of rat hearts transplanted after preservation in a high pressure gaseous mixture of carbon monoxide and oxygen. AB - We recently succeeded in resuscitating an extracted rat heart following 24-48 hours of preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). This study aimed to examine the function of rat hearts transplanted after being preserved in the high-pressure CO and O2 gas mixture. The hearts of donor rats were preserved in a chamber filled with CO and O2 under high pressure for 24 h (CO24h) or 48 h at 4 degrees C. For the positive control (PC) group, hearts immediately extracted from donor rats were used for transplantation. The preserved hearts were transplanted into recipient rats by heterotopic cervical heart transplantation. CO toxicity does not affect the grafts or the recipients. Light microscopy and [(18)F]-fluorodeoxyglucose positron emission tomography revealed that there were no significant differences in the size of the myocardial infarction or apoptosis of myocardial cells in post transplant hearts between the PC and CO24h groups. Furthermore, at 100 days after the transplantation, the heart rate, weight and histological staining of the post transplanted hearts did not differ significantly between the PC and CO24h groups. These results indicate that the function of rat hearts is well preserved after 24 hours of high-pressure preservation in a CO and O2 gas mixture. Therefore, high pressure preservation in a gas mixture can be a useful method for organ preservation. PMID- 27562459 TI - Pelobium manganitolerans gen. nov., sp. nov., isolated from sludge of a manganese mine. AB - A Gram-staining-negative, rod-shaped, motile by gliding and facultative anaerobic bacterial strain, YS-25T, was isolated from a sludge of a manganese mine. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain YS 25T formed a single branch within the strains of the family Sphingobacteriaceae and showed low similarities to Pedobacter arcticus CCTCC AB 2010223T (91.7 %), 'Pedobacter zeaxanthinifaciens' TDMA-5 (91.5 %), Pedobacter terricola DS-45T (90.9 %), Pedobacter ureilyticus THG-T11T (90.9 %), Pseudopedobacter beijingensis MCCC 1A01299T (90.8 %) and Pedobacter heparinus CCTCC AB 209030T (88.5 %). Strain YS-25T had some unique physiological and biochemical characteristics: facultative anaerobic, able to hydrolyse Tween 40, positive for cystine arylamidase and negative for mannose assimilation and beta-galactosidase. The polar lipids of strain YS-25T were phosphatidylethanolamine, aminolipid, two unknown lipids and two glycolipids. The presence of glycolipids and absence of sphingolipid were different from the Pedobacter and Pseudopedobacter strains. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1omega7c), unknown ECL 13.565, iso-C17 : 0 3-OH, iso-C17 : 1omega9c and anteiso C15 : 0. The genomic DNA G+C content was 42.0 mol%, and the only respiratory quinone was menaquinone 7. On the basis of polyphasic taxonomic analyses, strain YS-25T is considered to represent a novel genus and species, for which the name Pelobium manganitolerans gen. nov., sp. nov. is proposed. The type strain is YS 25T (=KCTC 52203T=CCTCC AB 2016051T). PMID- 27562458 TI - Clinical outcomes with ABO antibody titer variability in a multicenter study of ABO-incompatible kidney transplantation in the United Kingdom. AB - BACKGROUND: ABO blood group-incompatible kidney transplantation (ABOiKTx) outcomes are good, but complications are more common than in conventional transplantation. Regimens that use extracorporeal antibody removal therapy (EART) and enhanced immunosuppression are guided by titration of ABO blood group antibodies (using hemagglutination [HA] dilution assays), and these assays vary significantly in performance between centers. This study aims to describe the differences in titer measurement and the effect on clinical practice and outcomes. STUDY DESIGN AND METHODS: This multicentre, prospective cohort study of 100 ABOiKTx recipients assessed treatment and outcome data, including HA assay results measured retrospectively in a single central laboratory. RESULTS: Patient and allograft survival at 1 year was 99% and 94%, respectively. There were significant differences in the number of pretransplantation EART sessions in centers undertaking plasma exchange (PEx), compared with immunoadsorption (IA) (median, 6 vs. 4 sessions; p = 0.007). The pre-EART HA titer in both groups was the same when centrally assayed. The local HA assay used to guide treatment yielded significantly higher titers in centers undertaking PEx compared with IA (median, 128 vs. 32; p < 0.005). Patients undergoing PEx rather than IA were significantly more likely to suffer postoperative hematoma (12.9% vs. 1.8%; p = 0.05) or any perioperative collection requiring drainage (19.4% vs. 3.6%; p = 0.02). CONCLUSION: The colinearity of HA assay sensitivity with the receipt of PEx and EART limits some conclusions regarding the likely direction of causation. However, the association of differences in clinical practice with recognized perioperative complications of ABOiKTx identifies targets for further investigation and quality improvement. PMID- 27562460 TI - Changes in the prevalence and biofilm formation of Haemophilus influenzae and Haemophilus parainfluenzae from the respiratory microbiota of patients with sarcoidosis. AB - BACKGROUND: Healthy condition and chronic diseases may be associated with microbiota composition and its properties. The prevalence of respiratory haemophili with respect to their phenotypes including the ability to biofilm formation in patients with sarcoidosis was assayed. METHODS: Nasopharynx and sputum specimens were taken in 31 patients with sarcoidosis (average age 42.6 +/- 13), and nasopharynx specimens were taken in 37 healthy people (average age 44.6 +/- 11.6). Haemophili were identified by API-NH microtest and by the matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system. Biofilm was visualised by crystal violet staining and confocal scanning laser microscopy (CSLM). The statistical analysis was performed with Statgraphics Plus for Windows. RESULTS: In total, 30/31 patients with sarcoidosis and 31/37 healthy people were colonized by Haemophilus influenzae (6/30 vs. 1/31) and Haemophilus parainfluenzae (28/30 vs. 31/31) in the nasopharynx. The overall number of nasopharyngeal haemophili isolates was 59 in patients with sarcoidosis and 67 in healthy volunteers (H. influenzae 6/59 vs. 1/67, P = 0.05; H. parainfluenzae 47/59 vs. 65/67, P = 0.0032). Moreover, the decreased number of H. parainfluenzae biofilm-producing isolates was shown in nasopharyngeal samples in patients with sarcoidosis as compared to healthy people (19/31 vs. 57/65, P = 0.006), especially with respect to isolates classified as strong and very strong biofilm-producers (8/31 vs. 39/65, P = 0.002). CONCLUSIONS: The obtained data suggest that the qualitative and quantitative changes within the respiratory microbiota concerning the overall prevalence of H. influenzae together with the decreased number of H. parainfluenzae strains and the decreased rate of H. parainfluenzae biofilm-producing isolates as compared to healthy people may be associated with sarcoidosis. PMID- 27562462 TI - Tumour metabolism: Adapting to harsh conditions. PMID- 27562461 TI - The metabolic fate of acetate in cancer. AB - Recent high-profile reports have reignited an interest in acetate metabolism in cancer. Acetyl-CoA synthetases that catalyse the conversion of acetate to acetyl CoA have now been implicated in the growth of hepatocellular carcinoma, glioblastoma, breast cancer and prostate cancer. In this Review, we discuss how acetate functions as a nutritional source for tumours and as a regulator of cancer cell stress, and how preventing its (re)capture by cancer cells may provide an opportunity for therapeutic intervention. PMID- 27562464 TI - Tumour metabolism: Feeding your friends. PMID- 27562465 TI - Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-alpha and the RFC. AB - Folate deficiency in fetal life is strongly associated with structural malformations and linked to intrauterine growth restriction. In addition, limited availability of methyl donors, such as folate, during pregnancy may result in abnormal gene methylation patterns and contribute to developmental programming. The fetus is dependent on placental transfer of folate, however the molecular mechanisms regulating placental folate transport are unknown. We used cultured primary human trophoblast cells to test the hypothesis that mechanistic target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate folate transport by post translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal folate uptake. Folate uptake stimulated by insulin + IGF-1 was mediated by mTORC2 but did not involve mTORC1. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of FR-alpha and RFC transporter isoforms without affecting global protein expression. Inhibition of the ubiquitin ligase Nedd4-2 had no effect on folate transport. In conclusion, we report for the first time that mTORC1/C2 are positive regulators of cellular folate uptake by modulating the cell surface abundance of specific transporter isoforms. We propose that regulation of placental folate transport by mTOR signaling provide a direct link between placental function, gene methylation and fetal programming. PMID- 27562466 TI - Mesh complications and failure rates after transvaginal mesh repair compared with abdominal or laparoscopic sacrocolpopexy and to native tissue repair in treating apical prolapse. AB - OBJECTIVE: Our objective was to quantitate the extent of complications and failure rate for apical prolapse repair with transvaginal mesh (TVM) use versus sacrocolpopexy over a minimum of 2 years of follow-up. METHODS: Truven CCAE and Medicare Supplemental databases 2008-2013 were used for analysis. Patients with apical prolapse repair via transvaginal mesh (TVMR), abdominal sacrocolpopexy (ASCP), laparoscopic sacrocolpopexy (LSCP), or native tissue repair (NTR) and continuously enrolled for years were in the study cohort. Surgical failures were identified by reoperation for any prolapse or subsequent use of pessary. SAS(r) 9.3 was used for analysis. RESULTS: Mesh removal/revision was reported highest in TVMR (5.1 %), followed by LSCP (1.7 %) and ASCP (1.2 %). In those with concomitant sling, combined rates for mesh/sling revision were high, at 9.0 % in TVMR + sling, 5.6 % in ASCP + sling, and 4.5 % LSCP + sling. Sling-alone cases reported a 3.5 % revision rate. Pelvic pain (16.4-22.7 %) and dyspareunia (5.6 7.5 %) were high in all three approaches for apical prolapse repairs. Reoperation for apical prolapse was more common for TVMR (2.9 %) compared with NTR (2.3 %) [odds ratio (OR) 1.27; confidence interval (CI) 1.1-1.47; p 0.002]. Both ASCP and LSCP were superior to NTR (ASCP 1.5 %, OR 0.63, CI 0.46-0.86; p 0.003) and LSCP 1.8 % (OR 0.79, CI 0.62-1.01; p 0.07). Overall prolapse recurrence, as indicated by any compartment surgery for prolapse and/or pessary use, was also noted highest in TVMR (5.9 % OR 1.23, CI 1.11-1.36; p <0.0001). Laparoscopic sacrocolpopexies were slightly superior at 4.0 % overall recurrence (OR 0.83, CI 0.7-0.98); p 0.03). Failure of incontinence surgery was higher when the initial procedure combined prolapse and sling surgery (1.97 %) versus sling alone (1.6 %). CONCLUSIONS: Reoperation for apical prolapse is more common with TVMR than with sacrocolpopexies and NTR. Incontinence procedures are more likely to fail when performed along with prolapse repair than when performed alone. When mesh is used for repair, mesh revision is highest with TVMR and lowest with ASCP. PMID- 27562468 TI - Special Issue on New Challenges for Catalysis from Theory to Experiment. PMID- 27562467 TI - Finite element model focused on stress distribution in the levator ani muscle during vaginal delivery. AB - INTRODUCTION AND HYPOTHESIS: During vaginal delivery, the levator ani muscle (LAM) undergoes severe deformation. This stress can lead to stretch-related LAM injuries. The objective of this study was to develop a sophisticated MRI-based model to simulate changes in the LAM during vaginal delivery. METHODS: A 3D finite element model of the female pelvic floor and fetal head was developed. The model geometry was based on MRI data from a nulliparous woman and 1-day-old neonate. Material parameters were estimated using uniaxial test data from the literature and by least-square minimization method. The boundary conditions reflected all anatomical constraints and supports. A simulation of vaginal delivery with regard to the cardinal movements of labor was then performed. RESULTS: The mean stress values in the iliococcygeus portion of the LAM during fetal head extension were 4.91-7.93 MPa. The highest stress values were induced in the pubovisceral and puborectal LAM portions (mean 27.46 MPa) at the outset of fetal head extension. The last LAM subdivision engaged in the changes in stress was the posteromedial section of the puborectal muscle. The mean stress values were 16.89 MPa at the end of fetal head extension. The LAM was elongated by nearly 2.5 times from its initial resting position. CONCLUSIONS: The cardinal movements of labor significantly affect the subsequent heterogeneous stress distribution in the LAM. The absolute stress values were highest in portions of the muscle that arise from the pubic bone. These areas are at the highest risk for muscle injuries with long-term complications. PMID- 27562463 TI - The interplay between cell signalling and the mevalonate pathway in cancer. AB - The mevalonate (MVA) pathway is an essential metabolic pathway that uses acetyl CoA to produce sterols and isoprenoids that are integral to tumour growth and progression. In recent years, many oncogenic signalling pathways have been shown to increase the activity and/or the expression of MVA pathway enzymes. This Review summarizes recent advances and discusses unique opportunities for immediately targeting this metabolic vulnerability in cancer with agents that have been approved for other therapeutic uses, such as the statin family of drugs, to improve outcomes for cancer patients. PMID- 27562469 TI - Nitrogen removal from synthetic wastewater using single and mixed culture systems of denitrifying fungi, bacteria, and actinobacteria. AB - The aim of this study was to investigate the effects of single and mixed culture of denitrifying fungi, bacteria, and actinobacteria on nitrogen removal and N2O emission in treatment of wastewater. Denitrifying endophytes of Pseudomonas sp. B2, Streptomyces sp. A9, and Fusarium sp. F3 isolated from rice plants were utilized for treatment of synthetic wastewater containing nitrate and nitrite. Experiments were conducted under shaking and static conditions. Results showed that under the static condition, more than 97 % of nitrate removal efficiencies were reached in all the treatments containing B2. The nitrate removal rates within the first 12 h in the treatments of B2, B2+A9, B2+F3, and B2+A9+F3 were 7.3, 9.8, 11, and 11 mg L-1 h-1, respectively. Under the shaking condition, 100 % of nitrite was removed in all the treatments containing B2. The presence of A9 and F3 with B2 increased the nitrite removal rates under both the shaking and static conditions. Compared to the B2 system, the mixed systems of B2+A9, B2+F3, and B2+A9+F3 reduced N2O emission (78.4 vs. 19.4, 1.80, and 0.03 MUM in 4 weeks, respectively). Our results suggested that B2 is an important strain that enhances nitrogen removal from wastewater. Mixed cultures of B2 with A9 and F3 can remove more nitrate and nitrite from wastewater and reduce nitrite accumulation and N2O emission in the denitrification process. PMID- 27562470 TI - Antimicrobial activity, cytotoxicity and chemical analysis of lemongrass essential oil (Cymbopogon flexuosus) and pure citral. AB - The aim of this study was to determine the antimicrobial effects of lemongrass essential oil (C. flexuosus) and to determine cytotoxic effects of both test compounds on human dermal fibroblasts. Antimicrobial susceptibility screening was carried out using the disk diffusion method. Antimicrobial resistance was observed in four of five Acinetobacter baumannii strains with two strains confirmed as multi-drug-resistant (MDR). All the strains tested were susceptible to both lemongrass and citral with zones of inhibition varying between 17 to 80 mm. The mean minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of citral (mic-0.14 % and mbc-0.3 % v/v) was lower than that of Lemongrass (mic-0.65 % and mbc-1.1 % v/v) determined using the microtitre plate method. Cell viability using human dermal fibroblasts (HDF; 106-05a) was determined following exposure to both compounds and a control (Grapeseed oil) using the XTT assay and the IC50 determined at 0.095 % (v/v) for citral and 0.126 % (v/v) for lemongrass. Grapeseed oil had no effect on cell viability. Live cell imaging was performed using the LumaScope 500 imaging equipment and changes in HDF cell morphology such as necrotic features and shrinkage were observed. The ability of lemongrass essential oil (EO) and citral to inhibit and kill MDR A. baumannii highlights its potential for use in the management of drug-resistant infections; however, in vitro cytotoxicity does suggest further tests are needed before in vivo or ex vivo human exposure. PMID- 27562471 TI - Long-term effects of CuO nanoparticles on the surface physicochemical properties of biofilms in a sequencing batch biofilm reactor. AB - In this study, we examined the long-term effects of copper oxide nanoparticles (CuO NPs) on the production and properties of EPS and the resulting variations in surface physicochemical characteristics of biofilms in a sequencing batch biofilm reactor. After exposure to 50 mg/L CuO NPs for 45 days, the protein (PRO) and polysaccharide (PS) contents in loosely bound EPS (LB-EPS) decreased as the production of LB-EPS decreased from 34.4 to 30 mg TOC/g EPS. However, the production of tightly bound EPS (TB-EPS) increased by 16.47 % as the PRO and PS contents increased. The content of humic-like substances (HS) increased significantly, becoming the predominant constituent in EPS with the presence of 50 mg/L CuO NPs. Furthermore, the results of three-dimensional excitation emission fluorescence spectra confirmed the various changes in terms of the LB EPS and TB-EPS contents after exposure to CuO NPs. Fourier transform infrared spectroscopy showed that the -OH and -NH2 groups of proteins in EPS were involved in the reaction with CuO NPs. Moreover, the chronic exposure to CuO NPs induced a negative impact on the flocculating efficiency of EPS and on the hydrophobicity and aggregation ability of microbial cells. The PRO/PS ratios of different EPS fractions were consistent with their hydrophobicities (R 2 >0.98) and bioflocculating efficiencies (R 2 >0.95); however, there was no correlation with aggregation ability. Additionally, the presence of bovine serum albumin (BSA) prevented the physical contact between CuO NPs and EPS as a result of NP aggregation and electrostatic repulsion. PMID- 27562472 TI - Impact of different type of cancer treatment on the effectiveness of breast reconstruction. AB - For women undergoing mastectomy as part of their breast cancer treatment, breast reconstruction is an important part of therapy. However, neoadjuvant, adjuvant treatments as well as other patient-related factors can compromise the results of breast reconstruction techniques. In this article we have reviewed current approaches to the management of complications and risks that neoadjuvant and adjuvant therapies pose on breast reconstruction after mastectomy for breast cancer. Non-treatment related factors influencing reconstruction techniques were reviewed as well. PMID- 27562473 TI - Alarming attrition rates among HIV-infected individuals in pre-antiretroviral therapy care in Myanmar, 2011-2014. AB - BACKGROUND: High retention rates have been documented among patients receiving antiretroviral therapy (ART) in Myanmar. However, there is no information on human immunodeficiency virus (HIV)-infected individuals in care before initiation of ART (pre-ART care). We assessed attrition (loss-to-follow-up [LTFU] and death) rates among HIV-infected individuals in pre-ART care and their associated factors over a 4-year period. DESIGN: In this retrospective cohort study, we extracted routinely collected data of HIV-infected adults (>15 years old) entering pre-ART care (June 2011-June 2014) as part of an Integrated HIV Care (IHC) programme, Myanmar. Attrition rates per 100 person-years and cumulative incidence of attrition were calculated. Factors associated with attrition were examined by calculating hazard ratios (HRs). RESULTS: Of 18,037 HIV-infected adults enrolled in the IHC programme, 11,464 (63%) entered pre-ART care (60% men, mean age 37 years, median cluster of differentiation 4 (CD4) cell count 160 cells/uL). Of the 11,464 eligible participants, 3,712 (32%) underwent attrition of which 43% were due to deaths and 57% were due to LTFU. The attrition rate was 78 per 100 person years (95% CI, 75-80). The cumulative incidence of attrition was 70% at the end of a 4-year follow-up, of which nearly 90% occurred in the first 6 months. Male sex (HR 1.5, 95% CI 1.4-1.6), WHO clinical Stage 3 and 4, CD4 count <200 cells/uL, abnormal BMI, and anaemia were statistically significant predictors of attrition. CONCLUSIONS: Pre-ART care attrition among persons living with HIV in Myanmar was alarmingly high - with most attrition occurring within the first 6 months. Strategies aimed at improving early HIV diagnosis and initiation of ART are needed. Suggestions include comprehensive nutrition support and intensified monitoring to prevent pre-ART care attrition by tracking patients who do not return for pre-ART care appointments. It is high time that Myanmar moves towards a 'test and treat' approach and ultimately eliminates the need for pre-ART care. PMID- 27562474 TI - Examining the prevalence of metabolic syndrome among overweight/obese African American breast cancer survivors vs. matched non-cancer controls. AB - PURPOSE: Metabolic Syndrome (MetS) is more predominant in overweight, obese and minority populations. This study examined the prevalence of MetS in an exclusively African-American (AA) cohort of breast cancer (BC) survivors; an underrepresented group in previous studies demonstrating negative BC outcomes disparities for females with MetS. METHODS: Using a case-control design, overweight/obese AA women with treated Stage I-IIIa BC were matched 1:1 on age, race, sex, and body mass index (BMI) category with non-cancer population controls (n = 444). Three of the following conditions were used to define MetS: HDL cholesterol <50 mg/dL (1.3 mmol/L), serum triglycerides >=150 mg/dL (1.7 mmol/L), blood glucose >=100 mg/dL (or on treatment), waist circumference >=88 cm, or >=130 mmHg systolic or >=85 mmHg diastolic blood pressure (or on treatment). Matched-pairs analyses were conducted. RESULTS: For BC cases, most women had self reported Stage I (n = 76) or Stage II (n = 91) disease and were 6.9 (+/-5.2) years post-diagnosis. MetS was significantly lower in BC survivors vs. their non cancer population controls (43.2 vs. 51.4 %, respectively; p < 0.05). The diagnosis of MetS did not differ by BMI stratification. A lower prevalence of >=2 risk factors (80.2 vs. 85.6 %, p < 0.05) was observed for all cases vs. CONTROLS: CONCLUSIONS: While MetS occurred less frequently in our BC cases vs. non-cancer controls, our estimates are nearly two times those reported in other BC survivors, suggesting important racial/ethnic differences. IMPLICATIONS FOR CANCER SURVIVORS: The prognostic implications of MetS among AA BC survivors remain unknown and warrant further investigation. PMID- 27562475 TI - Quality of life and symptoms in long-term survivors of colorectal cancer: results from NSABP protocol LTS-01. AB - PURPOSE: Little is known about health-related quality of life (HRQL) in long-term survivors (LTS) of colorectal cancer (CRC). METHODS: Long-term CRC survivors (>=5 years) treated in previous National Surgical Adjuvant Breast and Bowel Project trials were recruited from 60 sites. After obtaining consent, a telephone survey was administered, which included HRQL instruments to measure physical health (Instrumental Activities of Daily Living [IADL], SF-12 Physical Component Scale [PCS], SF-36 Vitality Scale), mental health (SF-12 Mental Component Scale [MCS], Life Orientation Test, and Impact of Cancer), and clinical symptoms (Fatigue Symptom Inventory [FSI], European Organization for Research and Treatment of Cancer Colorectal Module [EORTC-CR38], and Brief Pain Inventory). A multivariable model identified predictors of overall quality of life (global health rating). RESULTS: Participants (N = 708) had significantly higher HRQL compared with age group-matched non-cancer controls with higher mean scores on SF-12 PCS (49.5 vs. 43.7, p = <0.05), MCS (55.6 vs. 52.1, p = <0.05), and SF-36 Vitality Scale (67.1 vs. 59.9, p = <0.05). Multivariable modeling has demonstrated that better overall physical and mental health (PCS and MCS), positive body image (EORTC-CR38 scale), and less fatigue (FSI), were strongly associated with overall quality of life as measured by the global health rating. Interestingly, ability to perform IADLs, experience of cancer, gastrointestinal complaints, and pain, were not important predictors. CONCLUSIONS: In long-term CRC survivors, overall physical and mental health was excellent compared with general population. Other disease-related symptoms did not detract from good overall health. IMPLICATIONS FOR CANCER SURVIVORS: LTS of CRC within the setting of a clinical trial have higher HRQL than the general population, and treatment regimens do not appear to be associated with any significant late effects on quality of life. TRIAL REGISTRATION: NSABP LTS-01: NCT00410579. PMID- 27562476 TI - Ice VII from aqueous salt solutions: From a glass to a crystal with broken H bonds. AB - It has been known for decades that certain aqueous salt solutions of LiCl and LiBr readily form glasses when cooled to below ~160 K. This fact has recently been exploited to produce a " salty " high-pressure ice form: When the glass is compressed at low temperatures to pressures higher than 4 GPa and subsequently warmed, it crystallizes into ice VII with the ionic species trapped inside the ice lattice. Here we report the extreme limit of salt incorporation into ice VII, using high pressure neutron diffraction and molecular dynamics simulations. We show that high-pressure crystallisation of aqueous solutions of LiCl?RH2O and LiBr?RH2O with R = 5.6 leads to solids with strongly expanded volume, a destruction of the hydrogen-bond network with an isotropic distribution of water dipole moments, as well as a crystal-to-amorphous transition on decompression. This highly unusual behaviour constitutes an interesting pathway from a glass to a crystal where translational periodicity is restored but the rotational degrees of freedom remaining completely random. PMID- 27562477 TI - Therapeutic exercises for affecting post-treatment swallowing in people treated for advanced-stage head and neck cancers. AB - BACKGROUND: Head and neck cancer treatment has developed over the last decade, with improved mortality and survival rates, but the treatments often result in dysphagia (a difficulty in swallowing) as a side effect. This may be acute, resolving after treatment, or remain as a long-term negative sequela of head and neck cancer (HNC) treatment. Interventions to counteract the problems associated with dysphagia include swallowing exercises or modification of diet (bolus texture, size), or both. OBJECTIVES: To determine the effects of therapeutic exercises, undertaken before, during and/or immediately after HNC treatment, on swallowing, aspiration and adverse events such as chest infections, aspiration pneumonia and profound weight loss, in people treated curatively for advanced stage (stage III, stage IV) squamous cell carcinoma of the head and neck. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6); MEDLINE; PubMed; Embase; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; Web of Science; ClinicalTrials.gov; ICTRP; speechBITE; Google Scholar; Google and additional sources for published and unpublished trials. The date of the search was 1 July 2016. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of adults with head and neck cancer (stage III, stage IV) who underwent therapeutic exercises for swallowing before, during and/or immediately after HNC treatment to help produce safe and efficient swallowing. The main comparison was therapeutic exercises versus treatment as usual (TAU). Other possible comparison pairs included: therapeutic exercises versus sham exercises and therapeutic exercises plus TAU versus TAU. TAU consisted of reactive management of a patient's dysphagia, when this occurred. When severe, this included insertion of either a percutaneous endoscopic gastroscopy or nasogastric tube for non-oral feeding. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: safety and efficiency of oral swallowing, as measured by reduced/no aspiration; oropharyngeal swallowing efficiency (OPSE) measures, taken from videofluoroscopy swallowing studies; and adverse events, such as chest infections, aspiration pneumonia and profound weight loss. Secondary outcomes were time to return to function (swallowing); self-reported changes to quality of life; changes to psychological well-being - depression, anxiety and stress; patient satisfaction with the intervention; patient compliance with the intervention; and cost-effectiveness of the intervention. MAIN RESULTS: We included six studies (reported as seven papers) involving 326 participants whose ages ranged from 39 to 83 years, with a gender bias towards men (73% to 95% across studies), reflecting the characteristics of patients with HNC. The risk of bias in the studies was generally high.We did not pool data from studies because of significant differences in the interventions and outcomes evaluated. We found a lack of standardisation and consistency in the outcomes measured and the endpoints at which they were evaluated.We found no evidence that therapeutic exercises were better than TAU, or any other treatment, in improving the safety and efficiency of oral swallowing (our primary outcome) or in improving any of the secondary outcomes.Using the GRADE system, we classified the overall quality of the evidence for each outcome as very low, due to the limited number of trials and their low quality. There were no adverse events reported that were directly attributable to the intervention (swallowing exercises). AUTHORS' CONCLUSIONS: We found no evidence that undertaking therapeutic exercises before, during and/or immediately after HNC treatment leads to improvement in oral swallowing. This absence of evidence may be due to the small participant numbers in trials, resulting in insufficient power to detect any difference. Data from the identified trials could not be combined due to differences in the choice of primary outcomes and in the measurement tools used to assess them, and the differing baseline and endpoints across studies.Designing and implementing studies with stronger methodological rigour is essential. There needs to be agreement about the key primary outcomes, the choice of validated assessment tools to measure them and the time points at which those measurements are made. PMID- 27562478 TI - Radiation doses to operators performing transjugular intrahepatic portosystemic shunt using a flat-panel detector-based system and ultrasound guidance for portal vein targeting. AB - OBJECTIVES: The aim of this study was to prospectively evaluate effective dose (E) of operators performing transjugular intrahepatic portosystemic shunts (TIPS) in a single centre. Patients' radiation exposure was also collected. METHODS: Between 8/2015 and 6/2016, 45 consecutive TIPS were performed in adult patients using a flat-panel detector-based system (FPDS) and real-time ultrasound guidance (USG) for portal vein targeting. Electronic personal dosimeters were used to measure radiation doses to the primary and assistant operators, anaesthesia nurse and radiographer. Patients' radiation exposure was measured with dose area product (DAP); fluoroscopy time (FT) was also collected. RESULTS: Mean E for the primary operator was 1.40 MUSv (SD 2.68, median 0.42, range 0.12 - 12.18), for the assistant operator was 1.29 MUSv (SD 1.79, median 0.40, range 0.10 - 4.89), for the anaesthesia nurse was 0.21 MUSv (SD 0.67, median 0.10, range 0.03 - 3.99), for the radiographer was 0.42 MUSv (SD 0.71, median 0.25, range 0.03 - 2.67). Mean patient DAP was 59.31 GyCm2 (SD 56.91, median 31.58, range 7.66 - 281.40); mean FT was 10.20 min (SD 7.40, median 10.40, range 3.8 - 31.8). CONCLUSION: The use of FPDS and USG for portal vein targeting allows a reasonably low E to operators performing TIPS. KEY POINTS: * The operators' E vary according to the complexity of the procedure. * FPDS and USG allow a reasonably low E to TIPS operators. * FPDS and USG have an important role in reducing the occupational exposure. PMID- 27562479 TI - CT imaging before transcatheter aortic valve implantation (TAVI) using variable helical pitch scanning and its diagnostic performance for coronary artery disease. AB - OBJECTIVES: To evaluate the effectiveness of CT before TAVI using variable helical pitch (VHP) scanning and its diagnostic performance for coronary artery disease (CAD). METHODS: Sixty patients (84.4 +/- 4.6 years) scheduled for TAVI underwent CT using VHP scanning with the contrast material (CM) volume calculated as scanning time * weight [kg] * 0.06 mL. Retrospective electrocardiography (ECG) gated scanning was utilized to examine the thorax, and non-ECG-gated scanning of the abdomen immediately followed. We analyzed CT attenuation values of the coronary arteries, aorta, iliac and femoral arteries. The coronary CT angiography images were evaluated for the presence of stenosis (>=50 %); invasive coronary angiography served as a reference standard. RESULTS: The average attenuations of all of the arteries were greater than 400 HU. We could evaluate the peripheral access vessels and dimensions of the ascending aorta, aortic root, and aortic annulus in all patients. The average volume of CM was 38.7 +/- 8.5 mL. On per patient and vessel analysis, CT showed 91.7 % and 89.5 % sensitivity, and 91.3 % and 97.4 % negative predictive value (NPV). CONCLUSIONS: CT using VHP scanning with an average CM volume of 38.7 mL is useful before TAVI and had a high sensitivity and NPV in excluding obstructive CAD. KEY POINTS: * TAVI-planning CT using variable helical pitch (VHP) scanning is useful. * The average volume of contrast material was 38.7 +/- 8.5 mL. * The average attenuations of all the arteries were >400 HU. * This CT had a high sensitivity and NPV for excluding obstructive CAD. PMID- 27562480 TI - Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus 90Y-radioembolization for hepatocellular carcinoma. AB - OBJECTIVE: To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 (90Y) radioembolization for hepatocellular carcinoma (HCC). METHODS: Studies comparing conventional (c)TACE versus 90Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. RESULTS: Fourteen studies comparing DEB-TACE or 90Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. CONCLUSION: DEB-TACE and 90Y radioembolization are efficacious treatments for patients suffering from HCC; DEB TACE demonstrated survival benefit at 1-year compared to 90Y-radioembolization but direct comparison is warranted for further evaluation. KEY POINTS: * This meta-analysis shows greater 1-year survival benefit for DEB-TACE over 90 Y radioembolization. * DEB-TACE has a favourable 2- & 3-year survival benefit trend over 90 Y-radioembolization. * No significant difference for tumour response was detected. * Direct comparison of these methods for a more robust evaluation is warranted. PMID- 27562481 TI - Effects of maternal dietary egg intake during early lactation on human milk ovalbumin concentration: a randomized controlled trial. AB - BACKGROUND: There is limited understanding of how maternal diet affects breastmilk food allergen concentrations, and whether exposure to allergens through this route influences the development of infant oral tolerance or sensitization. OBJECTIVE: To investigate how maternal dietary egg ingestion during early lactation influences egg protein (ovalbumin) levels detected in human breastmilk. METHODS: In a randomized controlled trial, women were allocated to a dietary group for the first six weeks of lactation: high-egg diet (> 4 eggs per week), low-egg diet (one-three eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6 weeks of lactation for the measurement of ovalbumin. The permeability of the mammary epithelium was assessed by measuring the breastmilk sodium : potassium ratio. Egg-specific IgE and IgG4 were measured in infant plasma at 6 weeks, and prior to the introduction of egg in solids at 16 weeks. RESULTS: Average maternal egg ingestion was associated with breastmilk ovalbumin concentration. Specifically, for each additional egg ingested per week, there was an average 25% increase in ovalbumin concentration (95% CI: 5-48%, P = 0.01). Breastmilk ovalbumin concentrations were significantly higher in the 'high egg' group (> 4 eggs per week) compared with the 'egg-free' group (P = 0.04). However, one-third of women had no breastmilk ovalbumin detected. No detectable associations were found between mammary epithelium permeability and breastmilk ovalbumin concentrations. Infant plasma egg-specific IgG4 levels were also positively associated with maternal egg ingestion, with an average 22% (95% CI: 3 45%) increase in infant egg-specific IgG4 levels per additional egg consumed per week (P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Increased maternal egg ingestion is associated with increased breastmilk ovalbumin, and markers of immune tolerance in infants. These results highlight the potential for maternal diet to benefit infant oral tolerance development during lactation. PMID- 27562482 TI - Towards Interactive Medical Content Delivery Between Simulated Body Sensor Networks and Practical Data Center. AB - With the development of IoT (Internet of Thing), big data analysis and cloud computing, traditional medical information system integrates with these new technologies. The establishment of cloud-based smart healthcare application gets more and more attention. In this paper, semi-physical simulation technology is applied to cloud-based smart healthcare system. The Body sensor network (BSN) of system transmit has two ways of data collection and transmission. The one is using practical BSN to collect data and transmitting it to the data center. The other is transmitting real medical data to practical data center by simulating BSN. In order to transmit real medical data to practical data center by simulating BSN under semi-physical simulation environment, this paper designs an OPNET packet structure, defines a gateway node model between simulating BSN and practical data center and builds a custom protocol stack. Moreover, this paper conducts a large amount of simulation on the real data transmission through simulation network connecting with practical network. The simulation result can provides a reference for parameter settings of fully practical network and reduces the cost of devices and personnel involved. PMID- 27562483 TI - A Distinguishing Arterial Pulse Waves Approach by Using Image Processing and Feature Extraction Technique. AB - Traditional Chinese Medicine (TCM) is based on five main types of diagnoses methods consisting of inspection, auscultation, olfaction, inquiry, and palpation. The most important one is palpation also called pulse diagnosis which is to measure wrist artery pulse by doctor's fingers for detecting patient's health state. In this paper, it is carried out by using a specialized pulse measuring instrument to classify one's pulse type. The measured pulse waves (MPWs) were segmented into the arterial pulse wave curve (APWC) by image proposing method. The slopes and periods among four specific points on the APWC were taken to be the pulse features. Three algorithms are proposed in this paper, which could extract these features from the APWCs and compared their differences between each of them to the average feature matrix, individually. These results show that the method proposed in this study is superior and more accurate than the previous studies. The proposed method could significantly save doctors a large amount of time, increase accuracy and decrease data volume. PMID- 27562484 TI - Cooperative wireless network control based health and activity monitoring system. AB - A real-time cooperative communication based wireless network is presented for monitoring health and activity of an end-user in their environment. The cooperative communication offers better energy consumption and also an opportunity to aware the current location of a user non-intrusively. The link between mobile sensor node and relay node is dynamically established by using Received Signal Strength Indicator (RSSI) and Link Quality Indicator (LQI) based on adaptive relay selection scheme. The study proposes a Linear Acceleration based Transmission Power Decision Control (LA-TPDC) algorithm to further enhance the energy efficiency of cooperative communication. Further, the occurrences of false alarms are carefully prevented by introducing three stages of sequential warning system. The real-time experiments are carried-out by using the nodes, namely mobile sensor node, relay nodes and a destination node which are indigenously developed by using a CC430 microcontroller integrated with an in built transceiver at 868 MHz. The wireless node performance characteristics, such as energy consumption, Signal-Noise ratio (SNR), Bit Error Rate (BER), Packet Delivery Ratio (PDR) and transmission offset are evaluated for all the participated nodes. The experimental results observed that the proposed linear acceleration based transmission power decision control algorithm almost doubles the battery life time than energy efficient conventional cooperative communication. PMID- 27562485 TI - Intermittent Demand Forecasting in a Tertiary Pediatric Intensive Care Unit. AB - Forecasts of the demand for medical supplies both directly and indirectly affect the operating costs and the quality of the care provided by health care institutions. Specifically, overestimating demand induces an inventory surplus, whereas underestimating demand possibly compromises patient safety. Uncertainty in forecasting the consumption of medical supplies generates intermittent demand events. The intermittent demand patterns for medical supplies are generally classified as lumpy, erratic, smooth, and slow-moving demand. This study was conducted with the purpose of advancing a tertiary pediatric intensive care unit's efforts to achieve a high level of accuracy in its forecasting of the demand for medical supplies. On this point, several demand forecasting methods were compared in terms of the forecast accuracy of each. The results confirm that applying Croston's method combined with a single exponential smoothing method yields the most accurate results for forecasting lumpy, erratic, and slow-moving demand, whereas the Simple Moving Average (SMA) method is the most suitable for forecasting smooth demand. In addition, when the classification of demand consumption patterns were combined with the demand forecasting models, the forecasting errors were minimized, indicating that this classification framework can play a role in improving patient safety and reducing inventory management costs in health care institutions. PMID- 27562486 TI - Repeated nonanesthetic malignant hyperthermia reactions in a child. AB - A series of life-threatening nonanesthetic-related MH reactions in a child was the inspiration for a proactive, novel solution allowing for early prehospital, potentially lifesaving intravenous dantrolene administration. Multidisciplinary collaboration is essential and parent education must be comprehensive and ongoing. This case underlines the importance of considering nonanesthetic MH susceptibility in the child who has a history of unspecified myopathy and who presents with fever and total body stiffness. PMID- 27562487 TI - RETRACTED ARTICLE: Molecular Characterization of Prunus angustifolia Genotypes from Turkey. PMID- 27562488 TI - Distinct patterns of primary and motile cilia in Rathke's cleft cysts and craniopharyngioma subtypes. AB - Cilia are highly conserved organelles, which serve critical roles in development and physiology. Motile cilia are expressed in a limited range of tissues, where they principally regulate local extracellular fluid dynamics. In contrast, primary cilia are expressed by many vertebrate cell types during interphase, and are intimately involved in the cell cycle and signal transduction. Notably, primary cilia are essential for vertebrate hedgehog pathway activity. Improved detection of motile cilia may assist in the diagnosis of some pathologic entities such as Rathke's cleft cysts, whereas characterizing primary cilia in neoplastic tissues may implicate cilia-dependent signaling pathways as critical for tumorigenesis. We show that immunohistochemistry for the nuclear transcription factor FOXJ1, a master regulator of motile ciliogenesis, robustly labels the motile ciliated epithelium of Rathke's cleft cysts. FOXJ1 expression discriminates Rathke's cleft cysts from entities in the sellar/suprasellar region with overlapping histologic features such as craniopharyngiomas. Co immunohistochemistry for FOXJ1 and markers that highlight motile cilia such as acetylated tubulin (TUBA4A) and the small GTPase ARL13B further enhance the ability to identify diagnostic epithelial cells. In addition to highlighting motile cilia, ARL13B immunohistochemistry also robustly highlights primary cilia in formalin-fixed paraffin-embedded sections. Primary cilia are present throughout the neoplastic epithelium of adamantinomatous craniopharyngioma, but are limited to basally oriented cells near the fibrovascular stroma in papillary craniopharyngioma. Consistent with this differing pattern of primary ciliation, adamantinomatous craniopharyngiomas express significantly higher levels of SHH, and downstream targets such as PTCH1 and GLI2, compared with papillary craniopharyngiomas. In conclusion, motile ciliated epithelium can be readily identified using immunohistochemistry for FOXJ1, TUBA4A, and ARL13B, facilitating the diagnosis of Rathke's cleft cysts. Primary cilia can be identified by ARL13B immunohistochemistry in routine pathology specimens. The widespread presence of primary cilia in adamantinomatous craniopharyngioma implicates cilia-dependent hedgehog signaling in the pathogenesis of adamantinomatous craniopharyngioma. PMID- 27562489 TI - Evaluation of three commercial progesterone receptor assays in a single tamoxifen treated breast cancer cohort. AB - Estrogen receptor and progesterone receptor status are routinely assessed using immunohistochemistry assays to assist in patient prognosis and clinical management. Three commonly utilized autostainer vendors-Dako, Leica and Ventana provide ready-to-use progesterone receptor assays; however, they have never been directly compared in a single breast cancer cohort. We looked at three immunohistochemical progesterone receptor assays, in addition to original ligand binding assay results, in a single retrospective, tamoxifen-treated breast cancer cohort to investigate inter- and intra-observer agreement, concordance, prognostic ability and measures of test performance. All immunohistochemical assays utilized the manufacturer's specified protocols. Five-year disease-free survival was the endpoint of interest, and multivariate models were adjusted for lymph node status, tumor grade, tumor size and human epidermal growth factor 2 status. All assays showed substantial to almost perfect agreement between the three observers (Dako kappa=0.69-0.90; Leica kappa=0.70-0.89; and Ventana kappa=0.78-0.94) and concordance (Dako/Leica kappa=0.81; Dako/Ventana kappa=0.78; and Leica/Ventana kappa=0.82). Univariate survival analyses showed that only the ligand-binding assay, Dako and Ventana assays achieved statistical significance. No statistically significant results were seen in multivariate models, although a strong trend was seen with the Ventana progesterone receptor assay. All assays performed similarly with regards to measures of test performance with ligand binding assay set as the reference, and all immunohistochemical assays outperformed the ligand-binding assay in regards to 5-year disease-free survival. Despite similar agreement and concordance with the progesterone receptor assays, clear differences were noted with regards to 5-year disease-free survival. Additional survival analyses suggest that clinical utility of estrogen receptor assays vary when investigated in combination with progesterone receptor. PMID- 27562490 TI - TERT promoter mutations and prognosis in solitary fibrous tumor. AB - Solitary fibrous tumor is a mesenchymal neoplasm exhibiting a broad spectrum of biological behavior and harboring the NAB2-STAT6 fusion. Clinicopathologic parameters are currently used in risk-prediction models for solitary fibrous tumor, but the molecular determinants of malignancy in solitary fibrous tumors remain unknown. We proposed that the activation of telomere maintenance pathways confers a perpetual malignant phenotype to these tumors. Therefore, we investigated telomerase reverse transcriptase (TERT) reactivation induced by promoter mutations as a potential molecular mechanism for aggressive clinical behavior in solitary fibrous tumor. The retrospective study included tumor samples from 94 patients with solitary fibrous tumor (31 thoracic and 63 extra thoracic). Follow-up information was available for 68 patients (median, 46 months). TERT promoter mutation analysis was performed by PCR and Sanger sequencing, and TERT mRNA expression was assessed by real-time quantitative reverse transcription PCR. Patients were stratified into clinicopathologic subgroups (high-risk (n=20), moderate-risk (n=28), and low-risk (n=46)) according to the risk-stratification model proposed by Demicco et al. TERT promoter mutations were identified in 26 of 94 (28%) solitary fibrous tumors: -124C>T in 23 tumors (88%), -124C>A in 1 tumor (4%), and -146C>T in 2 tumors (8%). Real-time quantitative reverse transcription PCR revealed that TERT mRNA expression was higher in all solitary fibrous tumors with the mutant TERT promoter than those with the wild-type TERT promoter. TERT promoter mutations were strongly associated with high-risk clinicopathologic characteristics and outcome. An adverse event (relapse, death) occurred in 16 of 68 (24%) patients, 12 with solitary fibrous tumors with TERT promoter mutations and 4 with the wild-type TERT promoter. TERT promoter mutations were strongly associated with older age (P=0.006), larger tumor size (P=0.000002), higher risk classifications (P=2.9 * 10-9), and a worse event-free survival (P=0.0082). Thus, TERT promoter mutations in solitary fibrous tumor influence gene expression and are associated with adverse patient outcome. Integrating TERT promoter mutational status with existing multivariable risk-prediction models might improve risk prediction in patients with solitary fibrous tumor. PMID- 27562491 TI - Concurrent ARID1A and ARID1B inactivation in endometrial and ovarian dedifferentiated carcinomas. AB - Dedifferentiated carcinoma of the endometrium or the ovary is an aggressive epithelial malignancy that comprises an endometrioid carcinoma together with an undifferentiated carcinoma. We recently reported that inactivation of BRG1 or INI1, core subunits of the switch/sucrose non-fermenting (SWI/SNF) complex, was the likely molecular event underlying dedifferentiation in about half of dedifferentiated carcinomas. In this study, we performed a genomic screen that included other members of the SWI/SNF complex to better delineate the molecular basis in the remainder of these tumours. We identified concurrent inactivating mutations involving ARID1A and ARID1B in 12 of 24 BRG1/INI1-intact, 0 of 3 INI1 deficient and 0 of 16 BRG1-deficient dedifferentiated carcinomas. All ARID1A and ARID1B co-mutated tumours displayed loss of ARID1A expression in the undifferentiated component with 11 of 12 tumours also displaying absent staining in the endometrioid component. ARID1B expression was absent in the undifferentiated component in all 12 tumours, whereas the corresponding endometrioid component showed intact expression. Clinically, ARID1A/ARID1B co inactivated tumours showed similar aggressive behaviour to BRG1 or INI1 inactivated tumours. Given that ARID1A and ARID1B are the only known DNA-binding subunits of the SWI/SNF-A complex, additional inactivation of ARID1B in an ARID1A deficient background appears to represent an alternative mechanism of disruption of SWI/SNF-mediated transcriptional regulation, resulting in arrested cellular differentiation in endometrial and ovarian endometrioid cancer. PMID- 27562492 TI - Erythroleukemia shares biological features and outcome with myelodysplastic syndromes with excess blasts: a rationale for its inclusion into future classifications of myelodysplastic syndromes. AB - Erythroleukemia was considered an acute myeloid leukemia in the 2008 World Health Organization (WHO) classification and is defined by the presence of >=50% bone marrow erythroblasts, having <20% bone marrow blasts from total nucleated cells but >=20% bone marrow myeloblasts from nonerythroid cells. Erythroleukemia shares clinicopathologic features with myelodysplastic syndromes, especially with erythroid-predominant myelodysplastic syndromes (>=50% bone marrow erythroblasts). The upcoming WHO revision proposes to eliminate the nonerythroid blast cell count rule and to move erythroleukemia patients into the appropriate myelodysplastic syndrome category on the basis of the absolute blast cell count. We conducted a retrospective study of patients with de novo erythroleukemia and compared their clinico-biological features and outcome with those of de novo myelodysplastic syndromes, focusing on erythroid-predominant myelodysplastic syndromes. Median overall survival of 405 erythroid-predominant myelodysplastic syndromes without excess blasts was significantly longer than that observed in 57 erythroid-predominant refractory anemias with excess blasts-1 and in 59 erythroleukemias, but no significant difference was observed between erythroid predominant refractory anemias with excess blasts-1 and erythroleukemias. In this subset of patients with >=50% bone marrow erythroblasts and excess blasts, the presence of a high-risk karyotype defined by the International Prognostic Scoring System or by the Revised International Prognostic Scoring System was the main prognostic factor. In the same way, the survival of 459 refractory anemias with excess blasts-2, independently of having >=20% bone marrow blasts from nonerythroid cells or not, was almost identical to the observed in 59 erythroleukemias. Interestingly, 11 low-blast count erythroleukemias with 5 to <10% bone marrow blasts from total nucleated cells showed similar survival than the rest of erythroleukemias. Our data suggest that de novo erythroleukemia is in the spectrum of myelodysplastic syndromes with excess blasts and support its inclusion into future classifications of myelodysplastic syndromes. PMID- 27562493 TI - MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. AB - Recurrent mutations in the myogenic transcription factor MYOD1 and PIK3CA were initially described in a subset of embryonal rhabdomyosarcomas. Recently, two independent studies demonstrated presence of MYODI (L122R) mutations as the basis to re-classify a spindle cell rhabdomyosarcoma, along with a sclerosing rhabdomyosarcoma, distinct from an embryonal rhabdomyosarcoma. We analyzed a much larger cohort of 49 primary rhabdomyosarcoma tumor samples of various subtypes, collected over a period of 9 years, for the presence of MYOD1 (L122R), PIK3CA (H1047), and PIK3CA (E542/E545) mutations, along with immunohistochemical analysis of desmin, myogenin, and MYOD1. Although activating PIK3CA mutations were absent across the sample set analyzed, we report 20% MYOD1 (L122R) mutation in rhabdomyosarcomas, found exclusively in 10 of 21 spindle cell and sclerosing rhabdomyosarcomas, occurring mostly in the head and neck region along with extremity sites (64%), than the paratesticular and intra-abdominal sites. Furthermore, while all 10 MYOD1 mutant spindle cell and sclerosing rhabdomyosarcoma samples showed diffuse and strong MYOD1 immunoexpression, 7 of 31 samples of rhabdomyosarcoma with wild-type MYOD1 were negative for MYOD1 expression. Clinically, a striking correlation was found between MYOD1 mutation and the clinical outcomes available for 15 of 21 cases: 5 of 7 patients with spindle cell and sclerosing rhabdomyosarcomas, harboring MYOD1 mutation, were alive-with-disease and 2 of 8 patients with spindle cell and sclerosing rhabdomyosarcomas, with mutant MYOD1, were free-of-disease. Taken together, we present the first report of MYOD1 (L122R) mutation in the largest cohort of 49 rhabdomyosarcomas reported so far, that are associated with a relatively aggressive clinical course. Moreover, consistent with the earlier two studies, this study further reinforces a relationship between spindle cell and the sclerosing rhabdomyosarcoma-now recognized as a single subtype, distinct from an embryonal rhabdomyosarcoma. PMID- 27562494 TI - ETV4 is a useful marker for the diagnosis of CIC-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions. AB - Subsets of primitive round-cell sarcomas remain difficult to diagnose and classify. Among these is a rare round-cell sarcoma that harbors a CIC gene rearrangement known as CIC-rearranged undifferentiated round-cell sarcoma, which is most commonly fused to the DUX4 gene. Owing to its aggressive clinical behavior and potential therapeutic implications, accurate identification of this novel soft tissue sarcoma is necessary. Definitive diagnosis requires molecular confirmation, but only a few centers are as yet able to perform this test. Several studies have shown that PEA3 subfamily genes, notably ETV4 (belonging to the family of ETS transcription factors), are upregulated in CIC-rearranged undifferentiated round-cell sarcomas. We performed a detailed immunohistochemical analysis to investigate ETV4 expression in CIC-rearranged undifferentiated round cell sarcomas and their potential mimics (especially Ewing sarcomas). The study cohort included 17 cases of CIC-rearranged undifferentiated round-cell sarcomas, and 110 tumors that morphologically mimic CIC-rearranged undifferentiated round cell sarcomas: 43 Ewing sarcomas, 25 alveolar rhabdomyosarcomas, 20 poorly differentiated round-cell synovial sarcomas, 10 desmoplastic round-cell tumors, 5 BCOR-CCNB3 sarcomas, 5 lymphoblastic lymphomas, and 2 rhabdoid tumors. All CIC rearranged undifferentiated round-cell sarcomas (on core needle biopsies and open biopsies) were ETV4-positive with a strong diffuse nuclear pattern. Among the other 110 tumors, only six cases (four Ewing sarcomas, one alveolar rhabdomyosarcoma, and one desmoplastic round-cell tumor) showed focal (<5% of tumor cells) and very weak nuclear expression of ETV4; all other tumors were completely negative for ETV4. We conclude that systematic immunohistochemical analysis of ETV4 makes it possible to diagnose undifferentiated round-cell sarcomas (with no molecular markers for sarcoma-associated translocation) such as CIC-rearranged undifferentiated round-cell sarcoma. PMID- 27562496 TI - Influence of decalcification procedures on immunohistochemistry and molecular pathology in breast cancer. AB - Distant breast cancer metastases are nowadays routinely biopsied to reassess receptor status and to isolate DNA for sequencing of druggable targets. Bone metastases are the most frequent subgroup. Decalcification procedures may negatively affect antigenicity and DNA quality. We therefore evaluated the effect of several decalcification procedures on receptor status and DNA/RNA quality. In 23 prospectively collected breast tumors, we compared ERalpha, PR and HER2 status by immunohistochemistry in (non-decalcified) tissue routinely processed for diagnostic purposes and in parallel tissue decalcified in Christensen's buffer with and without microwave, EDTA and Formical-4. Furthermore, HER2 fluorescence in situ hybridization and DNA/RNA quantity and quality were assessed. We found that the percentage of ERalpha-positive cells were on average lower in EDTA (P=0.049) and Formical-4 (P=0.047) treated cases, compared with controls, and PR expression showed decreased antigenicity after Christensen's buffer treatment (P=0.041). Overall, a good concordance (weighted kappa) was seen for ERalpha, PR and HER2 immunohistochemistry when comparing the non-decalcified control tissues with the decalcified tissues. For two patients (9%), there was a potential influence on therapeutic decision making with regard to hormonal therapy or HER2 targeted therapy. HER2 fluorescence in situ hybridization interpretation was seriously hampered by Christensen's buffer and Formical-4, and DNA/RNA quantity and quality were decreased after all four decalcification procedures. Validation on paired primary breast tumor specimens and EDTA-treated bone metastases showed that immunohistochemistry and fluorescence in situ hybridization were well assessable and DNA and RNA yield and quality were sufficient. With this, we conclude that common decalcification procedures have only a modest negative influence on hormone and HER2 receptor immunohistochemistry in breast cancer. However, they may seriously affect DNA/RNA-based diagnostic procedures. Overall, EDTA-based decalcification is therefore to be preferred as it best allows fluorescence in situ hybridization and DNA/RNA isolation. PMID- 27562495 TI - QSOX1 expression is associated with aggressive tumor features and reduced survival in breast carcinomas. AB - The biological role of quiescin sulfhydryl oxidase 1 (QSOX1) in tumor development is not well known, and its relation to breast cancer progression and prognosis is controversial. Here, our aim was to study the expression pattern and prognostic impact of QSOX1 in breast cancer, in relation to molecular subgroups and tumor cell proliferation. We examined a population-based series as part of the prospective Norwegian Breast Cancer Screening Program, including all women (50-69 years) diagnosed with breast cancer in one county of Norway during 1996-2003. QSOX1 expression was assessed by immunohistochemistry on tissue microarrays (n=458). Median follow-up time was 13 years. High expression of QSOX1 protein was associated with features of poor prognosis including high histologic grade, hormone receptor negativity, HER2 positivity, and increased tumor cell proliferation. High QSOX1 expression was further associated with reduced breast cancer-specific survival in both univariate and multivariate analysis, independent of molecular subtypes. High QSOX1 expression is a strong and independent factor of reduced survival in breast cancer, also reflected by elevated levels in more aggressive molecular subgroups. QSOX1 expression may represent a biomarker for aggressive disease and a potential treatment target. PMID- 27562499 TI - BioCatNet: A Database System for the Integration of Enzyme Sequences and Biocatalytic Experiments. AB - The development of novel enzymes for biocatalytic processes requires knowledge on substrate profile and selectivity; this can be derived from databases and from publications. Often, these sources lack time-course data for the substrate or product, and an unambiguous link between experiment and enzyme sequence. The lack of integrated, original data hampers the comprehensive analysis of enzyme kinetics and the evaluation of sequence-function relationships. In order to accelerate enzyme engineering, BioCatNet integrates protein sequence, protein structure, and experimental data for a given enzyme family. BioCatNet explicitly assigns the enzyme sequence to the experimental data, which consists of information on reaction conditions and time-course data. BioCatNet facilitates the consistent documentation of reaction conditions, the archiving of time-course data, and the efficient exchange of experimental data among collaborators. Data integration is demonstrated for three case studies by using the TEED (Thiamine diphosphate-dependent Enzymes Engineering Database). PMID- 27562497 TI - PD-L1 expression in basaloid squamous cell lung carcinoma: Relationship to PD-1+ and CD8+ tumor-infiltrating T cells and outcome. AB - PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8+ and PD-1+ tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8+ and PD-1+ tumor infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (kappa range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (kappa=0.883, and kappa=0.721). Expression of PD-L1 correlated with a high content of CD8+ and PD-1+ tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8+ and PD-1+ tumor infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8+ and PD-1+ tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay. PMID- 27562498 TI - Loss of PTEN expression in ERG-negative prostate cancer predicts secondary therapies and leads to shorter disease-specific survival time after radical prostatectomy. AB - The clinical course of prostate cancer is highly variable. Current prognostic variables, stage, and Gleason score have limitations in assessing treatment regimens for individual patients, especially in the intermediate-risk group of Gleason score 7. ERG:TMPRSS2 fusion and loss of PTEN are some of the most common genetic alterations in prostate cancer. Immunohistochemistry of PTEN and ERG has generated interest as a promising method for more precise outcome prediction but requires further validation in population-based cohorts. We studied the predictive value of ERG and PTEN expression by immunohistochemistry in two large radical prostatectomy cohorts comprising 815 patients with extensive follow-up information. Clinical end points were initiation of secondary therapy, overall survival, and disease-specific survival. Predictions of clinical outcomes were also assessed according to androgen receptor (AR) activity. PTEN loss, especially in ERG-negative cancers, predicted initiation of secondary treatments and shortened disease-specific survival time, as well as stratifying Gleason score 7 patients into different prognostic groups with regard to secondary treatments and disease-specific survival. High AR immunoreactivity in ERG-negative cancers with PTEN loss predicted worse disease-specific survival. We also observed that in Gleason score 7 ERG-negative cases with PTEN loss and high AR expression have significantly shorter disease-specific survival time compared with ERG-positive cases. Our conclusion is that loss of PTEN is a strong determining factor for shorter disease-specific survival time and initiation of secondary therapies after radical prostatectomy. The predictive value of PTEN immunoreactivity is further accentuated in ERG-negative cancers with high AR expression. Negative PTEN expression, accompanied by ERG status, can be used to stratify patients with Gleason score 7 into different survival groups. Assessment of PTEN and ERG status could provide an additional tool for initial diagnostics when determining the prognosis and subsequent follow-up regimen for patients treated by radical prostatectomy. PMID- 27562500 TI - Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms. AB - Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques. Graphical Abstract ?. PMID- 27562501 TI - Distance-of-Flight Mass Spectrometry: What, Why, and How? AB - Distance-of-flight mass spectrometry (DOFMS) separates ions of different mass-to charge (m/z) by the distance they travel in a given time after acceleration. Like time-of-flight mass spectrometry (TOFMS), separation and mass assignment are based on ion velocity. However, DOFMS is not a variant of TOFMS; different methods of ion focusing and detection are used. In DOFMS, ions are driven orthogonally, at the detection time, onto an array of detectors parallel to the flight path. Through the independent detection of each m/z, DOFMS can provide both wider dynamic range and increased throughput for m/z of interest compared with conventional TOFMS. The iso-mass focusing and detection of ions is achieved by constant-momentum acceleration (CMA) and a linear-field ion mirror. Improved energy focus (including turn-around) is achieved in DOFMS, but the initial spatial dispersion of ions remains unchanged upon detection. Therefore, the point source nature of surface ionization techniques could put them at an advantage for DOFMS. To date, three types of position-sensitive detectors have been used for DOFMS: a microchannel plate with a phosphorescent screen, a focal plane camera, and an IonCCD array; advances in detector technology will likely improve DOFMS figures-of-merit. In addition, the combination of CMA with TOF detection has provided improved resolution and duty factor over a narrow m/z range (compared with conventional, single-pass TOFMS). The unique characteristics of DOFMS can enable the intact collection of large biomolecules, clusters, and organisms. DOFMS might also play a key role in achieving the long-sought goal of simultaneous MS/MS. Graphical Abstract ?. PMID- 27562502 TI - Online Monitoring of Methanol Electro-Oxidation Reactions by Ambient Mass Spectrometry. AB - Online detection of methanol electro-oxidation reaction products [e.g., formaldehyde (HCHO)] by mass spectrometry (MS) is challenging, owing to the high salt content and extreme pH of the electrolyte solution as well as the difficulty in ionizing the reaction products. Herein we present an online ambient mass spectrometric approach for analyzing HCHO generated from methanol electro oxidation, taking the advantage of high salt tolerance of desorption electrospray ionization mass spectrometry (DESI-MS). It was found that HCHO can be detected as PhNHNH+=CH2 (m/z 121) by DESI after online derivatization with PhNHNH2. With this approach, the analysis of HCHO from methanol electro-oxidation by MS was carried out not only in acidic condition but also in alkaline media for the first time. Efficiencies of different electrodes for methanol oxidation at different pHs were also evaluated. Our results show that Au electrode produces more HCHO than Pt based electrodes at alkaline pH, while the latter have higher yields at acidic solution. The presented methodology would be of great value for elucidating fuel cell reaction mechanisms and for screening ideal fuel cell electrode materials. Graphical Abstract ?. PMID- 27562503 TI - Enhanced Lipidome Coverage in Shotgun Analyses by using Gas-Phase Fractionation. AB - A high resolving power shotgun lipidomics strategy using gas-phase fractionation and data-dependent acquisition (DDA) was applied toward comprehensive characterization of lipids in a hen ovarian tissue in an untargeted fashion. Using this approach, a total of 822 unique lipids across a diverse range of lipid categories and classes were identified based on their MS/MS fragmentation patterns. Classes of glycerophospholipids and glycerolipids, such as glycerophosphocholines (PC), glycerophosphoethanolamines (PE), and triglycerides (TG), are often the most abundant peaks observed in shotgun lipidomics analyses. These ions suppress the signal from low abundance ions and hinder the chances of characterizing low abundant lipids when DDA is used. These issues were circumvented by utilizing gas-phase fractionation, where DDA was performed on narrow m/z ranges instead of a broad m/z range. Employing gas-phase fractionation resulted in an increase in sensitivity by more than an order of magnitude in both positive- and negative-ion modes. Furthermore, the enhanced sensitivity increased the number of lipids identified by a factor of ~4, and facilitated identification of low abundant lipids from classes such as cardiolipins that are often difficult to observe in untargeted shotgun analyses and require sample-specific preparation steps prior to analysis. This method serves as a resource for comprehensive profiling of lipids from many different categories and classes in an untargeted manner, as well as for targeted and quantitative analyses of individual lipids. Furthermore, this comprehensive analysis of the lipidome can serve as a species- and tissue-specific database for confident identification of other MS-based datasets, such as mass spectrometry imaging. Graphical Abstract ?. PMID- 27562505 TI - Now or ... later: Perceptual data are not immediately forgotten during language processing. AB - Christiansen & Chater (C&C) propose that language comprehenders must immediately compress perceptual data by "chunking" them into higher-level categories. Effective language understanding, however, requires maintaining perceptual information long enough to integrate it with downstream cues. Indeed, recent results suggest comprehenders do this. Although cognitive systems are undoubtedly limited, frameworks that do not take into account the tasks that these systems evolved to solve risk missing important insights. PMID- 27562504 TI - Effect of LED photobiomodulation on fluorescent light induced changes in cellular ATPases and Cytochrome c oxidase activity in Wistar rat. AB - BACKGROUND: Fluorescent light exposure at night alters cellular enzyme activities resulting in health defects. Studies have demonstrated that light emitting diode photobiomodulation enhances cellular enzyme activities. OBJECTIVE: The objectives of this study are to evaluate the effects of fluorescent light induced changes in cellular enzymes and to assess the protective role of pre exposure to 670 nm LED in rat model. METHODS: Male Wistar albino rats were divided into 10 groups of 6 animals each based on duration of exposure (1, 15, and 30 days) and exposure regimen (cage control, exposure to fluorescent light [1800 lx], LED preexposure followed by fluorescent light exposure and only LED exposure). Na+-K+ ATPase, Ca2+ ATPase, and cytochrome c oxidase of the brain, heart, kidney, liver, and skeletal muscle were assayed. RESULTS: Animals of the fluorescent light exposure group showed a significant reduction in Na+-K+ ATPase and Ca2+ ATPase activities in 1 and 15 days and their increase in animals of 30-day group in most of the regions studied. Cytochrome c oxidase showed increase in their level at all the time points assessed in most of the tissues. LED light preexposure showed a significant enhancement in the degree of increase in the enzyme activities in almost all the tissues and at all the time points assessed. CONCLUSIONS: This study demonstrates the protective effect of 670 nm LED pre exposure on cellular enzymes against fluorescent light induced change. PMID- 27562506 TI - A code within a code: how codons influence mRNA stability. PMID- 27562507 TI - Hippocampal malrotation is an anatomic variant and has no clinical significance in MRI-negative temporal lobe epilepsy. AB - OBJECTIVE: There is considerable difficulty in diagnosing hippocampal malrotation (HIMAL), with different criteria of variable reliability. Here we assess qualitative and quantitative criteria in HIMAL diagnosis and explore the role of HIMAL in magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). METHODS: We studied the MRI of 155 adult patients with MRI-negative TLE and 103 healthy volunteers, and we asked (1) what are the qualitative and quantitative features that allow a reliable diagnosis of HIMAL, (2) how common is HIMAL in a normal control population, and (3) is HIMAL congruent with the epileptogenic side in MRI-negative TLE. RESULTS: We found that the features that are most correlated with the expert diagnosis of HIMAL are hippocampal shape change with hippocampal diameter ratio > 0.8, lack of normal lateral convex margin, and a deep dominant inferior temporal sulcus (DITS) with DITS height ratio > 0.6. In a blinded analysis, a consensus diagnosis of unilateral or bilateral HIMAL was made in 25 of 103 controls (24.3% of people, 14.6% of hippocampi-14 left, six right, 10 bilateral) that did not differ from 155 lesion-negative TLE patients where 25 had HIMAL (16.1% of patients, 11.6% of hippocampi-12 left, two right, 11 bilateral). Of the 12 with left HIMAL only, 9 had seizures arising from the left temporal lobe, whereas 3 had right-sided seizures. Of the two with right HIMAL only, both had seizures arising from the left temporal lobe. SIGNIFICANCE: HIMAL is an anatomic variant commonly found in controls. HIMAL is also an incidental nonpathologic finding in adult MRI-negative TLE and should not influence surgical decision making. PMID- 27562508 TI - The Melin school: a personal memoir by Edward Hacskaylo. AB - One of the pioneers of research on ectomycorrhizas in the mid-1900s was Elias Melin in Uppsala Sweden. The author spent a year in the Melin lab conducting his doctoral research. Here he describes that experience and the work of some others of the next generation of mycorrhiza researchers who also were members of the Melin lab. PMID- 27562510 TI - Human evolutionary history and contemporary evolutionary theory provide insight when assessing cultural group selection. AB - Richerson et al. provide a much needed roadmap for assessing cultural group selection (CGS) theory and for applying it to understanding variation between contemporary human groups. However, the current proposal lacks connection to relevant evidence from the human evolutionary record and requires a better integration with contemporary evolutionary theory. The article also misapplies the F st statistic. PMID- 27562509 TI - Clavulina-Membranomyces is the most important lineage within the highly diverse ectomycorrhizal fungal community of Abies religiosa. AB - Abies religiosa is an endemic conifer of Mexico, where its monodominant forests are the winter refuge of the monarch butterfly. Due to climate change, it has been estimated that by 2090, A. religiosa populations will decline by 96.5 %. To achieve success, reforestation programs should consider its ectomycorrhizal (ECM) fungi. We used ITS nrDNA sequences to identify the ECM fungi associated with A. religiosa and, based on its abundance and frequency, determined the diversity and community structure in a pure A. religiosa forest near Mexico City. Using sequence metadata, we inferred the species geographic distribution and host preferences. We conducted phylogenetic analyses of the Clavulinaceae (the most important family). The ECM community held 83 species, among which the richest genera were Inocybe (21 species), Tomentella (10 species), and Russula (8 species). Besides its low species richness, the Clavulina-Membranomyces lineage was the most dominant family. Clavulina cf. cinerea and Membranomyces sp. exhibited the highest relative abundance and relative frequency values. Phylogenetic analyses placed the Clavulinaceae genotypes in three different clades: one within Membranomyces and two within Clavulina. A meta-analysis showed that the majority of the ECM fungi (45.78 %) associated with A. religiosa in Mexico have also been sequenced from North America and are shared by Pinaceae and Fagaceae. In contrast, because they have not been sequenced previously, 32.2 % of the species have a restricted distribution. Here, we highlight the emerging pattern that the Clavulina-Membranomyces lineage is dominant in several ECM communities in the Neotropics, including Aldinia and Dicymbe legume tropical forests in the Guyana Shield, the Alnus acuminata subtropical communities, and the A. religiosa temperate forests in Mexico. PMID- 27562511 TI - Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead. AB - Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead. PMID- 27562512 TI - Simulation of phase explosion in the nanosecond laser ablation of aluminum. AB - HYPOTHESIS: Vaporization, spallation and phase explosion are considered to be the main mechanisms contributing to the nanosecond laser ablation of metals. The theory of homogeneous nucleation, together with the dynamics of target heating, allows a space-time resolved simulation of the phase explosion mechanism. METHODS: The thermal phenomena occurring at the target surface are studied within the framework of a thermodynamic continuum approach. A 20ns laser pulse of variable fluence and Gaussian time dependence was assumed. The temperature profile in the target external layers is studied through the heat diffusion equation. The vaporization from the surface is modeled assuming unsteady adiabatic expansion (UAE) of the vapor and a Monte Carlo (MC) method is used to describe the formation of liquid nanodroplets through phase explosion. RESULTS: Liquid nanodroplets in the ablated material are studied at different laser fluences. The size distribution of the nanodroplets formed in the phase explosion process is here reported and connections with experiments are discussed. PMID- 27562514 TI - Human and ant social behavior should be compared in a very careful way to draw valid parallels. AB - Gowdy & Krall provide an interesting discussion of evolutionary origins and consequences of ultrasociality. However, some of their statements concerning various features of ant and human social behavior do not adequately reflect present knowledge about the discussed issues, which include, among others, polyethism, cultural information transfer, within-group conflicts and resistance in ant societies, and reproductive division of labor in humans. Gowdy & Krall (G&K) provide an interesting discussion of evolutionary origins and consequences of ultrasociality, an advanced form of social behavior that evolved independently in both social insects and humans. Their reflections are thought-provoking, but some statements concerning various features of ant and human social behavior do not reflect adequately the present knowledge about the discussed issues. PMID- 27562513 TI - Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA. AB - We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes. A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycaemic controls. miRNAs were identified using microarray profiling and literature review and validated by quantitative PCR (qPCR). In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, miR-452 5p, miR-126-3p, miR-130b-3p, miR-148a-3p, miR-let-7a-5p and miR-let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase alpha1 (AMPKalpha1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKalpha1 expression was also decreased in placental tissues of IGDM. The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycaemia was very well controlled by current standards. Decreased expression of AMPKalpha1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at 1 month of age and, if persistent, may predispose offspring to future metabolic disease. PMID- 27562516 TI - The bottleneck may be the solution, not the problem. AB - As a highly consequential biological trait, a memory "bottleneck" cannot escape selection pressures. It must therefore co-evolve with other cognitive mechanisms rather than act as an independent constraint. Recent theory and an implemented model of language acquisition suggest that a limit on working memory may evolve to help learning. Furthermore, it need not hamper the use of language for communication. PMID- 27562517 TI - Analysis of the expression of the Wnt family of proteins and its modulatory role on cytokine expression in non activated and activated astroglial cells. AB - Despite the essential functions of astrocytes and the emerging relevance of the Wnt family of proteins in the CNS under physiological and pathological conditions, the astroglial expression of this family of proteins and its potential modulatory role on astroglial activation is almost unknown. Thus, we have evaluated the expression of all Wnt ligands, receptors and regulators, and the activation state of Wnt-related signaling pathways in non-activated and differentially activated astroglial cultures. We found that numerous Wnt ligands, receptors and regulators were expressed in non-activated astrocytes, while the Wnt-dependent pathways were constitutively active. Moreover, the expression of most detectable Wnt-related molecules and the activity of the Wnt-dependent pathways suffered post-activation variations which frequently depended on the activation system. Finally, the analysis of the effects exerted by Wnt1 and 5a on the astroglial expression of prototypical genes related to astroglial activation showed that both Wnt ligands increased the astroglial expression of interleukin 1beta depending on the experimental context, while did not modulate tumor necrosis factor alpha, interleukin 6, transforming growth factor beta1 and glial fibrillary acidic protein expression. These results strongly suggest that the Wnt family of proteins is involved in how astrocytes modulate and respond to the physiological and pathological CNS. PMID- 27562515 TI - Neurochemical compartmentalization within the pigeon basal ganglia. AB - The goals of this study were to use multiple informative markers to define and characterize the neurochemically distinct compartments of the pigeon basal ganglia, especially striatum and accumbens. To this end, we used antibodies against 12 different neuropeptides, calcium-binding proteins or neurotransmitter related enzymes that are enriched in the basal ganglia. Our results clarify boundaries between previously described basal ganglia subdivisions in birds, and reveal considerable novel heterogeneity within these previously described subdivisions. Sixteen regions were identified that each displayed a unique neurochemical organization. Four compartments were identified within the dorsal striatal region. The neurochemical characteristics support previous comparisons to part of the central extended amygdala, somatomotor striatum, and associational striatum of mammals, respectively. The medialmost part of the medial striatum, however, has several unique features, including prominent pallidal-like woolly fibers and thus may be a region unique to birds. Four neurochemically distinct regions were identified within the pigeon ventral striatum: the accumbens, paratubercular striatum, ventrocaudal striatum, and the ventral area of the lateral part of the medial striatum that is located adjacent to these regions. The pigeon accumbens is neurochemically similar to the mammalian rostral accumbens. The pigeon paratubercular and ventrocaudal striatal regions are similar to the mammalian accumbens shell. The ventral portions of the medial and lateral parts of the medial striatum, which are located adjacent to accumbens shell-like areas, have neurochemical characteristics as well as previously reported limbic connections that are comparable to the accumbens core. Comparisons to neurochemically identified compartments in reptiles, mammals, and amphibians indicate that, although most of the basic compartments of the basal ganglia were highly conserved during tetrapod evolution, uniquely avian compartments may exist as well. PMID- 27562519 TI - [Hospital-acquired anemia: Facts, consequences and prevention]. AB - Hospital-acquired anemia is common, especially in the most critically ill patients. It may be associated with poor patient outcomes. It may result from increased blood loss, impaired red cell production or reduced red cell life span. Multiple associated factors may contribute simultaneously or sequentially to the decrease in hemoglobin level. Some of them are related to the underlying disease and others are iatrogenic. Clinicians should be aware of the importance and consequences of iatrogenic anemia caused by diagnostic blood sampling. Strategies and measures to minimize iatrogenic blood loss should be prioritized. They may reduce the risk of developing anemia and then red blood cells transfusion requirement. PMID- 27562520 TI - [Red blood transfusion in palliative care situation]. AB - Anemia is frequent in oncology. We debate the decision-making process of erythrocyte transfusion in palliative care situation from a case report. A patient with a prostatic metastatic cancer was in palliative situation with asthenia and coronary symptom. We analyze, in this particular case that does not describe reality of normal practice, the decision-making process of erythrocyte transfusion. These transfusions were based, in this case, on the evaluation of oncology prognosis, the short-term vital threats, life project and clinical safety of the transfusion. The patient has received 5 erythrocyte transfusions in 4 months until a multidisciplinary meeting decided to stop transfusion because of poor prognostic situation and bad tolerance of the act. This patient could be a collegial model used to measure the reasonable nature of prescription depending on the purpose and the goal of the patient but does not allow generalization. Although there is low risk of erythrocyte shortage, it seems important to train doctors to reduce abusive transfusion and define transfusion thresholds. Different levels of erythrocyte transfusion security would raise the issue of management of several stocks. Erythrocyte transfusion in palliative care can be considered subject to prognostic information and the palliative aim of the transfusions, multidisciplinary decision-making, during short hospitalizations and with evaluation of the act and consequences for the patient. PMID- 27562518 TI - Ginkgolides and bilobalide protect BV2 microglia cells against OGD/reoxygenation injury by inhibiting TLR2/4 signaling pathways. AB - Ginkgolide and bilobalide are major trilactone constituent of Ginkgo biloba leaves and have been shown to exert powerful neuroprotective properties. The aims of this study were to observe the inhibitory effects of ginkgolide and bilobalide on the activation of microglial cells induced by oxygen-glucose deprivation and reoxygenation (OGD/R) and the specific mechanisms by which these effects are mediated. For detecting whether ginkgolide and bilobalide increased cell viability in a dose-dependent manner, BV2 cells were subjected to oxygen-glucose deprivation for 4 h followed by 3 h reoxygenation with various concentrations of drugs (6.25, 12.5, 25, 50, and 100 MUg/ml). The extent of apoptosis effect of OGD/R with or without ginkgolide and bilobalide treatment were also measured by Annexin V-FITC/PI staining. Similarly, the levels of pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 were detected using a specific Bio Plex ProTM Reagent Kit. The effects of ginkgolide and bilobalide on protein levels of TLR2/4, MyD88, p-TAK1, p-IKKbeta, p-IkBalpha, NF-kappaB p65, Bcl-2, Bax, Bak, RIP3, cleaved-Caspase-3, cleaved PARP-1 and cellular localization of NF kappaB p65 were evaluated by Western blot and double-labeled immunofluorescence staining, respectively. OGD/R significantly decreased the cell viability and increased the release of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha in BV2 microglia cells; these effects were suppressed by ginkgolide and bilobalide. Meanwhile, ginkgolide and bilobalide also attenuated the OGD/R-induced increases in TLR2, TLR4, MyD88, Bak, RIP3 levels and reversed cleaved caspase-3/caspase-3, Bax/Bcl-2 and cleaved PARP-1/PARP-1 ratio. Furthermore, ginkgolide and bilobalide also downregulated p-TAK1, p-IkBalpha, and p-IKKbeta and inhibited the OGD/R-induced transfer of NF-kappaB p65 from cytoplasm to nucleus in BV2 microglia cells. The results showed that ginkgolide and bilobalide can inhibit OGD/R-induced production of inflammatory factors in BV2 microglia cells by regulating the TLRs/MyD88/NF-kappaB signaling pathways and attenuating inflammatory response. The possible mechanism of anti-inflammatory and neuroprotective effects of ginkgolides results from the synergistic reaction among each monomer constituents. PMID- 27562521 TI - The neural control of respiration in lampreys. AB - This review focuses on past and recent findings that have contributed to characterize the neural networks controlling respiration in the lamprey, a basal vertebrate. As in other vertebrates, respiration in lampreys is generated centrally in the brainstem. It is characterized by the presence of a fast and a slow respiratory rhythm. The anatomical and the basic physiological properties of the neural networks underlying the generation of the fast rhythm have been more thoroughly investigated; less is known about the generation of the slow respiratory rhythm. Comparative aspects with respiratory generators in other vertebrates as well as the mechanisms of modulation of respiration in association with locomotion are discussed. PMID- 27562522 TI - Updating a gas dynamics model using estimates for California sea lions (Zalophus californianus). AB - Theoretical models are used to predict how breath-hold diving vertebrates manage O2, CO2, and N2 while underwater. One recent gas dynamics model used available lung and tracheal compliance data from various species. As variation in respiratory compliance significantly affects alveolar compression and pulmonary shunt, the current study objective was to evaluate changes in model output when using species-specific parameters from California sea lions (Zalophus californianus). We explored the effects of lung and dead space compliance on the uptake of N2, O2, and CO2 in various tissues during a series of hypothetical dives. The updated parameters allowed for increased compliance of the lungs and an increased stiffness in the trachea. When comparing updated model output with a model using previous compliance values, there was a large decrease in N2 uptake but little change in O2 and CO2 levels. Therefore, previous models may overestimate N2 tensions and the risk of gas-related disease, such as decompression sickness (DCS), in marine mammals. PMID- 27562523 TI - Infant lower extremity long bone growth rates: comparison of contemporary with early 20th century data using mixed effect models. AB - OBJECTIVES: Modern reference standards for long bone growth are lacking for infants (<=1 year). This study develops a quantitative framework to characterize lower extremity bone shaft growth during infancy based on radiographic images, and compares it to data from the 1930s. METHODS: Femoral, tibial, and fibular shaft length measurements (diaphysis plus metaphysis) were collected retrospectively from 70 infants on initial and follow-up skeletal surveys performed for suspected abuse (7/2005-2/2013). These serial skeletal survey data (SSSD) were compared to the Denver Child Research Council data (DCRCD), a 1930's longitudinal dataset from 80 infants. Mixed effects regression models were developed to estimate growth trajectories from these data. Growth trajectories and short-term (<=2 months) growth rates were compared. RESULTS: Statistically distinct models described the contemporary (SSSD) and historic (DCRCD) datasets; however, there was substantial overlap (77-90%) between their confidence bands for the three measured bones. Based on developed models, the average long bone shafts of the DCRCD are shorter at birth than SSSD (femur: 77.0 vs. 82.3 mm; tibia: 64.4 vs. 68.2 mm; fibula: 61.0 vs. 64.4 mm), but the DCRCD long bone growth rates are faster than SSSD (femur: 0.21 vs. 0.17 mm/day; tibia: 0.16 vs. 0.14 mm/day; fibula: 0.15 vs. 0.14 mm/day). Short-term growth rates of these bones decreased with age. The effect of sexual dimorphism on long bone growth during infancy was non-significant. CONCLUSION: This study provides reference standards for long bone growth rates during the dynamic period of infancy that may aid clinical assessment, and also inform research studies of disorders associated with altered skeletal growth. PMID- 27562525 TI - Detection of Choroidal Neovascularization in Central Serous Chorioretinopathy Using Optical Coherence Tomographic Angiography. AB - PURPOSE: To demonstrate the detection of choroidal neovascularization (CNV) in clinically diagnosed central serous chorioretinopathy (CSC) by optical coherence tomographic angiography (OCTA). METHODS: Seventy-five eyes of 70 patients were included. OCTA was performed on each patient. Two trained readers evaluated the images independently to confirm the diagnosis and identify CNV at the level of the outer retina. RESULTS: All studied eyes presented characteristics consistent with CSC based on eye examination and traditional imaging technologies, including fundus fluorescein angiography, which showed no evidence of CNV. However, OCTA revealed definite abnormal vascularization at the level of the outer retina in 8 eyes (10.7%) of 8 patients (11.4%). CONCLUSION: This study suggests that in some cases of CSC, OCTA could be an alternative option to detect CNV that is undetectable by other conventional imaging techniques. PMID- 27562524 TI - Lipid transfer proteins: classification, nomenclature, structure, and function. AB - The non-specific lipid transfer proteins (LTPs) constitute a large protein family found in all land plants. They are small proteins characterized by a tunnel-like hydrophobic cavity, which makes them suitable for binding and transporting various lipids. The LTPs are abundantly expressed in most tissues. In general, they are synthesized with an N-terminal signal peptide that localizes the protein to spaces exterior to the plasma membrane. The in vivo functions of LTPs are still disputed, although evidence has accumulated for a role in the synthesis of lipid barrier polymers, such as cuticular waxes, suberin, and sporopollenin. There are also reports suggesting that LTPs are involved in signaling during pathogen attacks. LTPs are considered as key proteins for the plant's survival and colonization of land. In this review, we aim to present an overview of the current status of LTP research and also to discuss potential future applications of these proteins. We update the knowledge on 3D structures and lipid binding and review the most recent data from functional investigations, such as from knockout or overexpressing experiments. We also propose and argument for a novel system for the classification and naming of the LTPs. PMID- 27562526 TI - Examining ubiquitinated peptide enrichment efficiency through an epitope labeled protein. AB - Ubiquitination is a dynamic process that is responsible for regulation of cellular responses to stimuli in a number of biological systems. Previous efforts to study this post-translational modification have focused on protein enrichment; however, recent research utilizes the presence of the di-glycine (Gly-Gly) remnants following trypsin digestion to immuno-enrich ubiquitinated peptides. Monoclonal antibodies developed to the cleaved ubiquitin modification epitope, (tert-butoxycarbonyl) glycylglycine (Boc-Gly-Gly-NHS)(1), are used to identify the Gly-Gly signature. Here, we have successfully generated the Boc-Gly-Gly-NHS modification and showed that when conjugated to a lysine containing protein, such as lysozyme, it can be applied as a standard protein to examine ubiquitinated peptide enrichment within a complex background. PMID- 27562528 TI - Cultural group selection in the light of the selection of extended behavioral patterns. AB - The cultural group selection hypothesis is supported by considerations of short term and long-term behavioral patterns of group members, and the short-term and long-term consequences of that behavior. The key to understanding cooperation lies in understanding that the effect of an extended behavioral pattern does not equal - and might even be opposite to - the added effects of its parts. PMID- 27562527 TI - Arabidopsis immune secretory pathways to powdery mildew fungi. AB - Innate immune responses in host plants begin with the recognition of pathogen specific nonself molecules and terminate with the secretion of immune molecules. In the dicotyledonous model plant, Arabidopsis thaliana, two distinct secretory pathways required for disease resistance to powdery mildew fungi have been identified so far. One is an exocytic pathway consisting of PEN1, SNAP33 and VAMP721/722 SNARE proteins, but the other is an efflux-mediated one composed of PEN2 atypical myrosinase and PEN3 ABC transporter. Based on the conservation of the mechanically same exocytic pathway in the monocotyledonous plant barely, the former is regarded as an ancient secretory pathway, whereas the latter is considered as a newly evolved one in the Brassicaceae family including Arabidopsis. We recently identified synaptotagmin 1 as an additional regulator of these two secretory pathways. With current results, we discuss how these two secretory pathways contribute to Arabidopsis immunity depending on fungal adaptedness to Arabidopsis. PMID- 27562530 TI - The interaction of beta-lactoglobulin with ciprofloxacin and kanamycin; a spectroscopic and molecular modeling approach. AB - A vast research has been conducted to find suitable and safe carriers for vital and pH-sensitive drugs including antibiotics. This article reports the use of easily accessible and abundant purified beta-lactoglobulin (beta-LG) protein as the potential carrier of widely used Kanamycin (Kana) and Ciprofloxacin (Cip) antibiotics. Spectroscopic techniques (Fluorescence, UV-vis, Circular Dichroism) combined with molecular docking were used to determine the binding mechanism of these drugs. Fluorescence studies showed moderate binding affinity with the calculated binding constants KCip = 60.1 (+/-0.2) * 103 M-1 and Kkana = 2.5 (+/ 0.6) * 103 M-1 with the order of Cip > Kana. Results of UV-vis were consistent with fluorescence measurements and demonstrated a stronger complexation for Cip rather than Kana. The secondary structure of beta-LG was preserved upon interaction with Kana; however, a reduction in beta-sheet content from 39.1 to 31.9% was convoyed with an increase in alpha-helix from 12.8 to 20.5% due to complexation of Cip. Molecular docking studies demonstrated that preferred binding sites of these drugs are not the same and several amino acids are involved in stabilizing the interaction. Based on the achieved results, Kana and Cip can spontaneously bind to beta-LG and this protein may serve as their transport vehicle. PMID- 27562529 TI - Obesity associated with increased brain age from midlife. AB - Common mechanisms in aging and obesity are hypothesized to increase susceptibility to neurodegeneration, however, direct evidence in support of this hypothesis is lacking. We therefore performed a cross-sectional analysis of magnetic resonance image-based brain structure on a population-based cohort of healthy adults. Study participants were originally part of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) and included 527 individuals aged 20-87 years. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white-matter volume, cortical thickness, and surface area. Results indicated that cerebral white-matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase of brain age of 10 years. There were no similar body mass index-related changes in cortical parameters. This study suggests that at a population level, obesity may increase the risk of neurodegeneration. PMID- 27562531 TI - Selenate and Nitrate Bioreductions Using Methane as the Electron Donor in a Membrane Biofilm Reactor. AB - Selenate (SeO4(2-)) bioreduction is possible with oxidation of a range of organic or inorganic electron donors, but it never has been reported with methane gas (CH4) as the electron donor. In this study, we achieved complete SeO4(2-) bioreduction in a membrane biofilm reactor (MBfR) using CH4 as the sole added electron donor. The introduction of nitrate (NO3(-)) slightly inhibited SeO4(2-) reduction, but the two oxyanions were simultaneously reduced, even when the supply rate of CH4 was limited. The main SeO4(2-)-reduction product was nanospherical Se(0), which was identified by scanning electron microscopy coupled to energy dispersive X-ray analysis (SEM-EDS). Community analysis provided evidence for two mechanisms for SeO4(2-) bioreduction in the CH4-based MBfR: a single methanotrophic genus, such as Methylomonas, performed CH4 oxidation directly coupled to SeO4(2-) reduction, and a methanotroph oxidized CH4 to form organic metabolites that were electron donors for a synergistic SeO4(2-)-reducing bacterium. PMID- 27562532 TI - Cellulose as an adhesion agent for the synthesis of lignin aerogel with strong mechanical performance, Sound-absorption and thermal Insulation. AB - The lignin aerogels that are both high porosity and compressibility would have promising implications for bioengineering field to sound-adsorption and damping materials; however, creating this aerogel had a challenge to adhesive lignin. Here we reported cellulose as green adhesion agent to synthesize the aerogels with strong mechanical performance. Our approach-straightforwardly dissolved in ionic liquids and simply regenerated in the deionized water-causes assembly of micro-and nanoscale and even molecule level of cellulose and lignin. The resulting lignin aerogels exhibit Young's modulus up to 25.1 MPa, high-efficiency sound-adsorption and excellent thermal insulativity. The successful synthesis of this aerogels developed a path for lignin to an advanced utilization. PMID- 27562534 TI - Agriculture and the energy-complexity spiral. AB - The study of cultural complexity is entwined with ancestors myths from contemporary cosmology. Gowdy & Krall expose this mythology by arguing that complexity emerged from economic changes following cultivation. There is more, however, to the development of cultural complexity. Complexity can emerge from abundant energy or from addressing societal problems, which compels still further energy production. PMID- 27562533 TI - Gene transduction in mammalian cells using Bombyx mori nucleopolyhedrovirus assisted by glycoprotein 64 of Autographa californica multiple nucleopolyhedrovirus. AB - Autographa californica multiple nucleopolyhedrovirus (AcMNPV), an alphabaculovirus, has been widely utilized for protein expression in not only insect cells but also mammalian cells. AcMNPV is closely related to Bombyx mori nucleopolyhedrovirus (BmNPV), and nucleotide sequences of AcMNPV genes have high similarity with those of BmNPV. However, the transduction of BmNPV into mammalian cells has not been reported. In this study, we constructed a recombinant BmNPV (BmNPVDeltabgp/AcGP64/EGFP) whose surface 64 kDa glycoprotein (BmGP64) was substituted with that from AcMNPV (AcGP64). BmNPVDeltabgp/AcGP64/EGFP also carried an EGFP gene under the control of the CMV promoter. BmNPVDeltabgp/AcGP64/EGFP successfully transduced HEK293T cells. In comparison, a control construct (BmNPVDeltabgp/BmGP64/EGFP) which possessed BmGP64 instead of AcGP64 did not express EGFP in HEK293T cells. The transduction efficiency of BmNPVDeltabgp/AcGP64/EGFP was lower than that of an AcMNPV based-BacMam GFP transduction control. This result indicates that AcGP64 facilitates BmNPV transduction into HEK293T cells. BmNPV can be prepared easily on a large scale because BmNPV can infect silkworm larvae without any special equipment, even though specific diet is needed for silkworm rearing. BmNPV gene transduction into mammalian cells can potentially be applied easily for gene delivery into mammalian cells. PMID- 27562535 TI - Transcriptomic SNP discovery for custom genotyping arrays: impacts of sequence data, SNP calling method and genotyping technology on the probability of validation success. AB - BACKGROUND: Single nucleotide polymorphism (SNP) discovery is an important goal of many studies. However, the number of 'putative' SNPs discovered from a sequence resource may not provide a reliable indication of the number that will successfully validate with a given genotyping technology. For this it may be necessary to account for factors such as the method used for SNP discovery and the type of sequence data from which it originates, suitability of the SNP flanking sequences for probe design, and genomic context. To explore the relative importance of these and other factors, we used Illumina sequencing to augment an existing Roche 454 transcriptome assembly for the Antarctic fur seal (Arctocephalus gazella). We then mapped the raw Illumina reads to the new hybrid transcriptome using BWA and BOWTIE2 before calling SNPs with GATK. The resulting markers were pooled with two existing sets of SNPs called from the original 454 assembly using NEWBLER and SWAP454. Finally, we explored the extent to which SNPs discovered using these four methods overlapped and predicted the corresponding validation outcomes for both Illumina Infinium iSelect HD and Affymetrix Axiom arrays. RESULTS: Collating markers across all discovery methods resulted in a global list of 34,718 SNPs. However, concordance between the methods was surprisingly poor, with only 51.0 % of SNPs being discovered by more than one method and 13.5 % being called from both the 454 and Illumina datasets. Using a predictive modeling approach, we could also show that SNPs called from the Illumina data were on average more likely to successfully validate, as were SNPs called by more than one method. Above and beyond this pattern, predicted validation outcomes were also consistently better for Affymetrix Axiom arrays. CONCLUSIONS: Our results suggest that focusing on SNPs called by more than one method could potentially improve validation outcomes. They also highlight possible differences between alternative genotyping technologies that could be explored in future studies of non-model organisms. PMID- 27562536 TI - Toward mechanistic models of action-oriented and detached cognition. AB - To be successful, the research agenda for a novel control view of cognition should foresee more detailed, computationally specified process models of cognitive operations including higher cognition. These models should cover all domains of cognition, including those cognitive abilities that can be characterized as online interactive loops and detached forms of cognition that depend on internally generated neuronal processing. PMID- 27562538 TI - Acute leukemia in pregnancy: a single institution experience with 23 patients. AB - Management of acute leukemia during pregnancy presents a considerable challenge. Herein, we review our experience of 23 patients diagnosed with acute leukemia; during pregnancy at the Mayo Clinic between 1962 and 2016. Ten (43.4%), seven (30.4%), and six (26.2%) patients were diagnosed in first, second, and third trimester, respectively. In approximately, 50% (n = 11) therapeutic terminations or spontaneous abortions occurred. Fifty percent (2/4) of patients diagnosed during either first or second trimester who delayed chemotherapy by greater than one week died during induction therapy. Eleven patients received chemotherapy while pregnant which led to four fetal losses and seven deliveries (five full term and two preterm deliveries). No congenital malformations were reported. Eighteen patients (78%) achieved complete remission. At a median follow up of 55 months, seven patients (30%) remain alive. In summary, we provide a comprehensive description of maternal and fetal outcomes and insight into management of acute leukemia during pregnancy. PMID- 27562537 TI - Equivalence between solar irradiance and solar simulators in aging tests of sunglasses. AB - BACKGROUND: This work is part of a broader research that focuses on ocular health. Three outlines are the basis of the pyramid that comprehend the research as a whole: authors' previous work, which has provided the public to self-check their own sunglasses regarding the ultraviolet protection compatible to their category; Brazilian national survey in order to improve nationalization of sunglasses standards; and studies conducted on revisiting requirements of worldwide sunglasses standards, in which this work is inserted. It is still controversial on the literature the ultraviolet (UV) radiation effects on the ocular media, but the World Health Organization has established safe limits on the exposure of eyes to UV radiation based on the studies reported in literature. Sunglasses play an important role in providing safety, and their lenses should provide adequate UV filters. Regarding UV protection for ocular media, the resistance-to-irradiance test for sunglasses under many national standards requires irradiating lenses for 50 uninterrupted hours with a 450 W solar simulator. This artificial aging test may provide a corresponding evaluation of exposure to the sun. METHODS: Calculating the direct and diffuse solar irradiance at a vertical surface and the corresponding radiant exposure for the entire year, we compare the latter with the 50-h radiant exposure of a 450 W xenon arc lamp from a solar simulator required by national standards. RESULTS: Our calculations indicate that this stress test is ineffective in its present form. CONCLUSIONS: We provide evidence of the need to re-evaluate the parameters of the tests to establish appropriate safe limits for UV irradiance. SIGNIFICANCE: This work is potentially significant for scientists and legislators in the field of sunglasses standards to improve the requirements of sunglasses quality and safety. PMID- 27562539 TI - Multibit MoS2 Photoelectronic Memory with Ultrahigh Sensitivity. AB - A novel multibit MoS2 photoelectronic nonvolatile memory device is developed by synergistically combining rational device designs and the efficient transfer of large-area MoS2 flakes. The MoS2 photoelectronic memory exhibits excellent memory characteristics, including a large programming/erasing current ratio that exceeds 107 , multilevel data storage of 3 bits (corresponding to eight levels), performance stability over 200 cycles, and stable data retention over 104 s. PMID- 27562540 TI - Adopting Quality Criteria for Websites Providing Medical Information About Rare Diseases. AB - BACKGROUND: The European Union considers diseases to be rare when they affect less than 5 in 10,000 people. It is estimated that there are between 5000 and 8000 different rare diseases. Consistent with this diversity, the quality of information available on the Web varies considerably. Thus, quality criteria for websites about rare diseases are needed. OBJECTIVE: The objective of this study was to generate a catalog of quality criteria suitable for rare diseases. METHODS: First, relevant certificates and quality recommendations for health information websites were identified through a comprehensive Web search. Second, all considered quality criteria of each certification program and catalog were examined, extracted into an overview table, and analyzed by thematic content. Finally, an interdisciplinary expert group verified the relevant quality criteria. RESULTS: We identified 9 quality certificates and criteria catalogs for health information websites with 304 single criteria items. Through this, we aggregated 163 various quality criteria, each assigned to one of the following categories: thematic, technical, service, content, and legal. Finally, a consensus about 13 quality criteria for websites offering medical information on rare diseases was determined. Of these categories, 4 (data protection concept, imprint, creation and updating date, and possibility to contact the website provider) were identified as being the most important for publishing medical information about rare diseases. CONCLUSIONS: The large number of different quality criteria appearing within a relatively small number of criteria catalogs shows that the opinion of what is important in the quality of health information differs. In addition, to define useful quality criteria for websites about rare diseases, which are an essential source of information for many patients, a trade off is necessary between the high standard of quality criteria for health information websites in general and the limited provision of information about some rare diseases. Finally, transparently presented quality assessments can help people to find reliable information and to assess its quality. PMID- 27562542 TI - Measurement and Modeling of Short and Medium Range Order in Amorphous Ta2O5 Thin Films. AB - Amorphous films and coatings are rapidly growing in importance. Yet, there is a dearth of high-quality structural data on sub-micron films. Not understanding how these materials assemble at atomic scale limits fundamental insights needed to improve their performance. Here, we use grazing-incidence x-ray total scattering measurements to examine the atomic structure of the top 50-100 nm of Ta2O5 films; mirror coatings that show high promise to significantly improve the sensitivity of the next generation of gravitational-wave detectors. Our measurements show noticeable changes well into medium range, not only between crystalline and amorphous, but also between as-deposited, annealed and doped amorphous films. It is a further challenge to quickly translate the structural information into insights into mechanisms of packing and disorder. Here, we illustrate a modeling approach that allows translation of observed structural features to a physically intuitive packing of a primary structural unit based on a kinked Ta-O-Ta backbone. Our modeling illustrates how Ta-O-Ta units link to form longer 1D chains and even 2D ribbons, and how doping and annealing influences formation of 2D order. We also find that all the amorphousTa2O5 films studied in here are not just poorly crystalline but appear to lack true 3D order. PMID- 27562541 TI - Single-molecule imaging of UvrA and UvrB recruitment to DNA lesions in living Escherichia coli. AB - Nucleotide excision repair (NER) removes chemically diverse DNA lesions in all domains of life. In Escherichia coli, UvrA and UvrB initiate NER, although the mechanistic details of how this occurs in vivo remain to be established. Here, we use single-molecule fluorescence imaging to provide a comprehensive characterization of the lesion search, recognition and verification process in living cells. We show that NER initiation involves a two-step mechanism in which UvrA scans the genome and locates DNA damage independently of UvrB. Then UvrA recruits UvrB from solution to the lesion. These steps are coordinated by ATP binding and hydrolysis in the 'proximal' and 'distal' UvrA ATP-binding sites. We show that initial UvrB-independent damage recognition by UvrA requires ATPase activity in the distal site only. Subsequent UvrB recruitment requires ATP hydrolysis in the proximal site. Finally, UvrA dissociates from the lesion complex, allowing UvrB to orchestrate the downstream NER reactions. PMID- 27562543 TI - GPs report missing payments for trainees' pay. PMID- 27562544 TI - Faithful conditional quantum state transfer between weakly coupled qubits. AB - One of the strengths of quantum information theory is that it can treat quantum states without referring to their particular physical representation. In principle, quantum states can be therefore fully swapped between various quantum systems by their mutual interaction and this quantum state transfer is crucial for many quantum communication and information processing tasks. In practice, however, the achievable interaction time and strength are often limited by decoherence. Here we propose and experimentally demonstrate a procedure for faithful quantum state transfer between two weakly interacting qubits. Our scheme enables a probabilistic yet perfect unidirectional transfer of an arbitrary unknown state of a source qubit onto a target qubit prepared initially in a known state. The transfer is achieved by a combination of a suitable measurement of the source qubit and quantum filtering on the target qubit depending on the outcome of measurement on the source qubit. We experimentally verify feasibility and robustness of the transfer using a linear optical setup with qubits encoded into polarization states of single photons. PMID- 27562545 TI - Lipid profiles in schizophrenia associated with clinical traits: a five year follow-up study. AB - BACKGROUND: Alterations in serum and membrane lipids may be involved in schizophrenia pathophysiology. It is not known whether lipid profiles are associated with disease severity or current symptom level. METHODS: Clinical and lipid data were gathered from 55 patients with schizophrenia admitted to psychiatric emergency wards in an acute stage of the disease (T1). The patients were re-examined after 5 years at a stable phase (T2). The clinical assessments included Positive and Negative Syndrome Scale (PANSS total, positive, negative) and Global Assessment of Functioning (GAF S, symptom and F, function). Serum lipids (cholesterol and triglyceride) and membrane polyunsaturated fatty acids (PUFA, LCPUFA) were measured. Healthy controls were recruited among hospital workers. RESULTS: Serum triglyceride was significantly higher in patients with schizophrenia compared to healthy controls both at T1 and T2 (p < 0.001), while serum cholesterol did not differ significantly. The levels of serum lipids in patients remained stable over time. At T1, serum lipids and symptoms were not significantly correlated. At T2, higher serum lipids were associated with more severe symptoms and poorer functioning. Higher serum lipid levels at T1 were associated with more severe symptoms and poorer functioning at T2; cholesterol with GAF-S (p < 0.05), triglyceride with PANSS total (p < 0.05), GAF-S (p < 0.01) and GAF-F (p < 0.01). Membrane lipids were significantly lower in the patient group compared to healthy controls at T1 (PUFA p < 0.001, LCPUFA p < 0.001), but not at T2. Membrane lipids were not significantly correlated with symptoms at T1, but significantly associated with negative symptoms and functioning at T2 as previously reported. CONCLUSIONS: The present findings suggest different roles of membrane and serum lipids in schizophrenia pathophysiology. To further elucidate the relation of lipid biology to disease traits, replication in independent studies of longitudinal samples are warranted. PMID- 27562547 TI - Stroke: Aortic stiffness predicts cognitive impairment. PMID- 27562548 TI - Neuromuscular disease: Mitochondrial dysfunction could precipitate motor neuron loss in spinal muscular atrophy. PMID- 27562546 TI - Eradication rates, risk factors, and implant selection in two-stage revision knee arthroplasty: a mid-term follow-up study. AB - BACKGROUND: Two-stage revision (TSR) knee arthroplasty is an established treatment, but failure to control infection still occurs in 4-50 % of cases. The aim of this study was to assess the infection eradication rate, risk factors for failure, and the clinical outcome after two-stage revision knee arthroplasty. METHODS: This retrospective study included 59 patients who had undergone at least one two-stage revision procedure due to periprosthetic joint infection (PJI). Demographic data, comorbidities, types of implant, and complications were analyzed. Univariate and multivariate logistic regression analysis were used to identify risk factors for failure. RESULTS: The infections were controlled in 55 patients (93.2 %). The follow-up period was 4.1 (+/-2.7) years. Infection control was achieved after the first TSR in 42 patients (71.2 %) and after the second TSR in 13 (76.5 %). The percentage of arthrodesis procedures in patients with infection control increased from 16.75 % after one TSR to 69.2 % after two TSRs. Multivariate logistic regression analysis identified body mass index (BMI) (odds ratio 1.22; 95 % confidence intervals, 1.07 to 1.40; p = 0.004) and smoking (OR 21.52; 95 % CI, 2.60 to 178.19; p = 0.004) as risk factors for failure. CONCLUSIONS: Two-stage revision protocols can achieve acceptable results even after a second procedure. It is still unclear whether the choice of implant influences failure rates. Risk factors for failure after two-stage revision were identified. Studies with larger sample sizes are needed in order to support these findings and identify further risk factors. To reduce failure rates, programs should be established to treat or minimize risk factors in patients with PJI. PMID- 27562549 TI - Epilepsy: Tau pathology found in temporal lobe epilepsy. PMID- 27562550 TI - Alzheimer disease: TREM-2 signalling and Alzheimer disease - striking the right balance. PMID- 27562551 TI - Neuromuscular disease: Benefit of thymectomy in myasthenia gravis. PMID- 27562552 TI - Multiple sclerosis: Successful trial of amiselimod for multiple sclerosis. PMID- 27562553 TI - A novel method to predict visual field progression more accurately, using intraocular pressure measurements in glaucoma patients. AB - Visual field (VF) data were retrospectively obtained from 491 eyes in 317 patients with open angle glaucoma who had undergone ten VF tests (Humphrey Field Analyzer, 24-2, SITA standard). First, mean of total deviation values (mTD) in the tenth VF was predicted using standard linear regression of the first five VFs (VF1-5) through to using all nine preceding VFs (VF1-9). Then an 'intraocular pressure (IOP)-integrated VF trend analysis' was carried out by simply using time multiplied by IOP as the independent term in the linear regression model. Prediction errors (absolute prediction error or root mean squared error: RMSE) for predicting mTD and also point wise TD values of the tenth VF were obtained from both approaches. The mTD absolute prediction errors associated with the IOP integrated VF trend analysis were significantly smaller than those from the standard trend analysis when VF1-6 through to VF1-8 were used (p < 0.05). The point wise RMSEs from the IOP-integrated trend analysis were significantly smaller than those from the standard trend analysis when VF1-5 through to VF1-9 were used (p < 0.05). This was especially the case when IOP was measured more frequently. Thus a significantly more accurate prediction of VF progression is possible using a simple trend analysis that incorporates IOP measurements. PMID- 27562554 TI - Past, Present, and Future of Informed Consent in Pain and Genomics Research: Challenges Facing Global Medical Community. AB - In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5-Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally. PMID- 27562555 TI - The status of the genus Pseudoroseovarius Sun et al. 2015. AB - The results of phylogenetic analyses of the genera Aliiroseovarius Park et al. 2015 and Pseudoroseovarius Sun et al. 2015 and comparison of the phenotypic features of their members showed that these genera should be united. Based on nomenclatural priority of the genus Aliiroseovarius, it is proposed to reclassify Pseudoroseovarius crassostreae as a later homotypic synonym of Aliiroseovarius crassostreae, Pseudoroseovarius halocynthiae as a later homotypic synonym of Aliiroseovarius halocynthiae, Pseudoroseovarius sediminilitoris as a later homotypic synonym of Aliiroseovarius sediminilitoris and Pseudoroseovarius zhejiangensis as Aliiroseovarius zhejiangensis comb. nov. PMID- 27562556 TI - Editor's Highlight: Metformin Protects Against Acetaminophen Hepatotoxicity by Attenuation of Mitochondrial Oxidant Stress and Dysfunction. AB - Overdose of acetaminophen (APAP) causes severe liver injury and even acute liver failure in both mice and human. A recent study by Kim et al. (2015, Metformin ameliorates acetaminophen hepatotoxicity via Gadd45beta-dependent regulation of JNK signaling in mice. J. Hepatol. 63, 75-82) showed that metformin, a first-line drug to treat type 2 diabetes mellitus, protected against APAP hepatotoxicity in mice. However, its exact protective mechanism has not been well clarified. To investigate this, C57BL/6J mice were treated with 400 mg/kg APAP and 350 mg/kg metformin was given 0.5 h pre- or 2 h post-APAP. Our data showed that pretreatment with metformin protected against APAP hepatotoxicity, as indicated by the over 80% reduction in plasma alanine aminotransferase (ALT) activities and significant decrease in centrilobular necrosis. Metabolic activation of APAP, as indicated by glutathione depletion and APAP-protein adducts formation, was also slightly inhibited. However, 2 h post-treatment with metformin still reduced liver injury by 50%, without inhibition of adduct formation. Interestingly, neither pre- nor post-treatment of metformin inhibited c-jun N-terminal kinase (JNK) activation or its mitochondrial translocation. In contrast, APAP-induced mitochondrial oxidant stress and dysfunction were greatly attenuated in these mice. In addition, mice with 2 h post-treatment with metformin also showed significant inhibition of complex I activity, which may contribute to the decreased mitochondrial oxidant stress. Furthermore, the protection was reproduced in JNK activation-absent HepaRG cells treated with 20 mM APAP followed by 0.5 or 1 mM metformin 6 h later, confirming JNK-independent protection mechanisms. Thus, metformin protects against APAP hepatotoxicity by attenuating the mitochondrial oxidant stress and subsequent mitochondrial dysfunction, and may be a potential therapeutic option for APAP overdose patients. PMID- 27562558 TI - From the Cover: Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats. AB - Volatile anesthetics can cause neuronal and glial toxicity in the developing mammalian brain, as well as long-term defects in learning and memory. The goals of this study were to compare anesthetics using a clinically relevant exposure paradigm, and to assess the anesthetic effects on hippocampal development and behavior. Our hypothesis was that volatile anesthetics disrupt hippocampal development, causing neurobehavioral defects later in life. Bromodeoxyuridine (BrdU) was administered to rats on postnatal day (P)1, and the rats were exposed to volatile anesthetics (isoflurane, sevoflurane, or desflurane) for 2 h on P2. On days P7 and P14, the BrdU-labeled cells were quantified in the hippocampal dentate gyrus using immunohistochemical assays and fluorescent microscopy. Caspase-3 positive cells were quantified on P2 to evaluate apoptosis. The remaining animals underwent behavioral testing at ages 6 weeks and 6 months, using the Morris Water Maze. Significantly fewer BrdU-positive cells were detected in the hippocampal dentate gyrus in both isoflurane and desflurane treated animals compared with controls at P7, but there were no changes in cell numbers after sevoflurane exposure. Cell counts for all three anesthetics compared with controls were equivalent at P14. Isoflurane or desflurane exposure yielded slight differences in the behavioral tests at 6 weeks, but no differences at 6 months post-exposure. We conclude that a single 2-h exposure at P2 to either isoflurane or desflurane causes a transient disruption of hippocampal neuronal development with no significant detectable long-term effects on learning and memory, whereas the same exposure to sevoflurane has no effects. PMID- 27562557 TI - Dose-Dependent Metabolic Reprogramming and Differential Gene Expression in TCDD Elicited Hepatic Fibrosis. AB - We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis, and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28 d or 92 d. RNA-Seq, ChIP-Seq (2 h), and 28 d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92 d. Additional vehicle and 30 ug/kg treatment groups were allowed to recover for 36 d following the 92-d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92 days, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1beta, -2, -4, -6, and -10, as well as TNF-alpha and IFN-gamma, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNA-Seq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. In summary, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD. PMID- 27562559 TI - Compensatory Renal Hypertrophy and the Uptake of Cysteine S-Conjugates of Hg2+ in Isolated S2 Proximal Tubular Segments. AB - Chronic kidney disease is characterized by a progressive and permanent loss of functioning nephrons. In order to compensate for this loss, the remaining functional nephrons undergo significant structural and functional changes. We hypothesize that luminal uptake of inorganic mercury (Hg2+), as a conjugate of cysteine (Cys; Cys-S-Hg-S-Cys), is enhanced in S2 segments of proximal tubules from the remnant kidney of uninephrectomized (NPX) rabbits. To test this hypothesis, we measured uptake and accumulation of Cys-S-Hg-S-Cys in isolated perfused S2 segments of proximal tubules from normal (control) and NPX rabbits. The remnant kidney in NPX rabbits undergoes significant hypertrophy during the initial 3 weeks following surgery. Tubules isolated from NPX rabbits were significantly larger in diameter and volume than those from control rabbits. Moreover, real-time PCR analyses of proximal tubules indicated that the expression of selected membrane transporters was greater in kidneys of NPX animals than in kidneys of control animals. When S2 segments from control and NPX rabbits were perfused with cystine or Cys-S-Hg-S-Cys, we found that the rates of luminal disappearance and tubular accumulation of Hg2+ were greater in tubules from NPX animals. These increases were inhibited by the addition of various amino acids to the perfusate. Taken together, our data suggest that hypertrophic changes in proximal tubules lead to an enhanced ability of these tubules to take up and accumulate Hg2. PMID- 27562560 TI - Editor's Highlight: Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded Samples. AB - Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here, we evaluated transcriptomic dose responses using RNA-sequencing in paired FFPE and frozen (FROZ) samples from 2 archival studies in mice, one <2 years old and the other >20 years old. Experimental treatments included 3 different doses of di(2 ethylhexyl)phthalate or dichloroacetic acid for the recently archived and older studies, respectively. Total RNA was ribo-depleted and sequenced using the Illumina HiSeq platform. In the recently archived study, FFPE samples had 35% lower total counts compared to FROZ samples but high concordance in fold-change values of differentially expressed genes (DEGs) (r2 = 0.99), highly enriched pathways (90% overlap with FROZ), and benchmark dose estimates for preselected target genes (<5% difference vs FROZ). In contrast, older FFPE samples had markedly lower total counts (3% of FROZ) and poor concordance in global DEGs and pathways. However, counts from FFPE and FROZ samples still positively correlated (r2 = 0.84 across all transcripts) and showed comparable dose responses for more highly expressed target genes. These findings highlight potential applications and issues in using RNA-sequencing data from FFPE samples. Recently archived FFPE samples were highly similar to FROZ samples in sequencing quality metrics, DEG profiles, and dose-response parameters, while further methods development is needed for older lower-quality FFPE samples. This work should help advance the use of archival resources in chemical safety and translational science. PMID- 27562561 TI - Chloride content of solutions used for regional citrate anticoagulation might be responsible for blunting correction of metabolic acidosis during continuous veno venous hemofiltration. AB - BACKGROUND: Citrate, the currently preferred anticoagulant for continuous veno venous hemofiltration (CVVH), may influence acid-base equilibrium. METHODS: The effect of 2 different citrate solutions on acid-base status was assessed according to the Stewart-Figge approach in two consecutive cohorts of critically ill adult patients. The first group received Prismocitrate 10/2 (PC10/2; 10 mmol citrate/L). The next group was treated with Prismocitrate 18/0 (PC18; 18 mmol citrate/L). Both groups received bicarbonate-buffered fluids in post-dilution. RESULTS: At similar citrate flow, the metabolic acidosis present at baseline in both groups was significantly attenuated in PC18 patients but persisted in PC10/2 patients after 24 h of treatment (median pH 7,42 vs 7,28; p = 0.0001). Acidosis in the PC10/2 group was associated with a decreased strong ion difference and an increased strong ion gap (respectively 43 vs. 51 mmol/L and 17 vs. 12 mmol/L, PC10/2 vs. PC18; both p = 0.001). Chloride flow was higher in PC10/2 than in PC18 subjects (25.9 vs 14.3 mmol/L blood; p < 0.05). CONCLUSION: Correction of acidosis was blunted in patients who received 10 mmol citrate/L as regional anticoagulation during CVVH. This could be explained by differences in chloride flow between the applied citrate solutions inducing hyperchloremic acidosis. PMID- 27562562 TI - Reply to "Implications of abnormal preoperative axillary imaging in the post Z011 era". PMID- 27562563 TI - Rooming-in for new mother and infant versus separate care for increasing the duration of breastfeeding. AB - BACKGROUND: Mother-infant proximity and interactions after birth and during the early postpartum period are important for breast-milk production and breastfeeding success. Rooming-in and separate care are both traditional practices. Rooming-in involves keeping the mother and the baby together in the same room after birth for the duration of hospitalisation, whereas separate care is keeping the baby in the hospital nursery and the baby is either brought to the mother for breastfeeding or she walks to the nursery. OBJECTIVES: To assess the effect of mother-infant rooming-in versus separation on the duration of breastfeeding (exclusive and total duration of breastfeeding). SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) investigating the effect of mother infant rooming-in versus separate care after hospital birth or at home on the duration of breastfeeding, proportion of breastfeeding at six months and adverse neonatal and maternal outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included one trial (involving 176 women) in this review. This trial included four groups with a factorial design. The factorial design took into account two factors, i.e. infant location in relation to the mother and the type of infant apparel. We combined three of the groups as the intervention (rooming-in) group and the fourth group acted as the control (separate care) and we analysed the results as a single pair-wise comparison. Primary outcomesThe primary outcome, duration of any breastfeeding, was reported by authors as median values because the distribution was found to be skewed. They reported the overall median duration of any breastfeeding to be four months, with no difference found between groups. Duration of exclusive breastfeeding and the proportion of infants being exclusively breastfed at six months of age was not reported in the trial. There was no difference found between the two groups in the proportion of infants receiving any breastfeeding at six months of age (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.51 to 1.39; one trial; 137 women; low-quality evidence). Secondary outcomesThe mean frequency of breastfeeds per day on day four postpartum for the rooming-in group was 8.3 (standard deviation (SD) 2.2), slightly higher than the separate care group, i.e. seven times per day. However, between-group comparison of this outcome was not appropriate since every infant in the separate care group was breastfed at a fixed schedule of seven times per day (SD = 0) resulting in no estimable comparison. The rate of exclusive breastfeeding on day four postpartum before discharge from hospital was significantly higher in the rooming-in group 86% (99 of 115) compared with separate care group, 45% (17 of 38), (RR 1.92; 95% CI 1.34 to 2.76; one trial, 153 women; low-quality evidence). None of our other pre-specified secondary outcomes were reported. AUTHORS' CONCLUSIONS: We found little evidence to support or refute the practice of rooming-in versus mother-infant separation. Further well-designed RCTs to investigate full mother-infant rooming-in versus partial rooming-in or separate care including all important outcomes are needed. PMID- 27562565 TI - Quantifying Phishing Susceptibility for Detection and Behavior Decisions. AB - OBJECTIVE: We use signal detection theory to measure vulnerability to phishing attacks, including variation in performance across task conditions. BACKGROUND: Phishing attacks are difficult to prevent with technology alone, as long as technology is operated by people. Those responsible for managing security risks must understand user decision making in order to create and evaluate potential solutions. METHOD: Using a scenario-based online task, we performed two experiments comparing performance on two tasks: detection, deciding whether an e mail is phishing, and behavior, deciding what to do with an e-mail. In Experiment 1, we manipulated the order of the tasks and notification of the phishing base rate. In Experiment 2, we varied which task participants performed. RESULTS: In both experiments, despite exhibiting cautious behavior, participants' limited detection ability left them vulnerable to phishing attacks. Greater sensitivity was positively correlated with confidence. Greater willingness to treat e-mails as legitimate was negatively correlated with perceived consequences from their actions and positively correlated with confidence. These patterns were robust across experimental conditions. CONCLUSION: Phishing-related decisions are sensitive to individuals' detection ability, response bias, confidence, and perception of consequences. Performance differs when people evaluate messages or respond to them but not when their task varies in other ways. APPLICATION: Based on these results, potential interventions include providing users with feedback on their abilities and information about the consequences of phishing, perhaps targeting those with the worst performance. Signal detection methods offer system operators quantitative assessments of the impacts of interventions and their residual vulnerability. PMID- 27562564 TI - Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution. AB - Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC tau 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB. PMID- 27562566 TI - Serum creatine kinase isoenzymes in children with osteogenesis imperfecta. AB - : This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. INTRODUCTION: The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. METHODS: This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. RESULTS: Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. CONCLUSIONS: This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs. PMID- 27562567 TI - Comparative efficacy of parathyroidectomy and active surveillance in patients with mild primary hyperparathyroidism: a systematic review and meta-analysis. AB - Counseling for patients with primary hyperparathyroidism (PHPT) and mild hypercalcemia without indications for surgical intervention requires accurate estimates of the potential benefits of parathyroidectomy. We aim to summarize the available evidence regarding the benefits of parathyroidectomy that patients with mild PHPT without indications for surgery experience compared to observation. We searched multiple databases from inception to August 2015. We included randomized controlled trials (RCT) and observational studies that evaluated changes in bone health, quality of life or neuropsychiatric symptoms, or in the risk of nephrolithiasis, cardiovascular events, or death between patients undergoing parathyroidectomy or active surveillance. Eight studies were eligible. Risk differences were not significant, in part due to lack of events (fractures, nephrolithiasis, cardiovascular events, or deaths). No significant differences were observed across measures of bone health, quality of life, and neuropsychiatric symptoms. A single RCT evaluating bone mineral density (BMD) changes at 5 years found a small statistically significant effect favoring parathyroidectomy. Patients with mild PHPT without indications for surgery experience a limited number of adverse consequences during short-term follow-up limiting our ability to estimate the benefit of surgery during this timeframe. This information is helpful as these patients consider surgery versus active surveillance. Long-term data is warranted to determine who benefits in the long run from surgical intervention and the extent to which this benefit affects outcomes that matter to patients. PMID- 27562569 TI - Arterial calcification due to CD73 deficiency (ACDC): imaging manifestations of ectopic mineralization. AB - Arterial calcification due to CD73 deficiency (ACDC) is a recently identified rare and debilitating adult-onset disorder caused by autosomal recessive NT5E gene mutations. ACDC is characterized by progressive and painful arterial calcifications primarily affecting the lower extremities, as well as calcifications affecting small joint capsules of the hands and feet. In this case report, the authors provide clinical follow-up for one of the first individuals identified by the National Institutes of Health (NIH) as having ACDC, focusing mainly on the imaging manifestations of periarticular joint mineralization, which are bilateral but slightly asymmetric, bulky up to the levels of the metacarpophalangeal and metatarsophalangeal joints, but smaller and more capsular in distribution at the proximal and distal interphalangeal joints, without erosive change or intra-articular mineralization. Differential considerations for similar appearing joint mineralization are provided. PMID- 27562570 TI - Potential use of (18)F-FDG-PET/CT to visualize hypermetabolism associated with muscle pain in patients with adult spinal deformity: a case report. AB - Patients with adult spinal deformity (ASD) are surgically treated for pain relief; however, visualization of the exact origin of the pain with imaging modalities is still challenging. We report the first case of a 60-year-old female patient who presented with painful degenerative kyphoscoliosis and was evaluated with flourine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) preoperatively. Because her low back pain was resistant to conservative treatment, she was treated with posterior spinal correction and fusion surgery from Th2 to the ilium. One year after the surgery, her low back pain had disappeared completely. In accordance with her clinical course, (18)F-FDG-PET imaging revealed the uptake of (18)F-FDG in the paravertebral muscles preoperatively and showed the complete absence of uptake at 1 year after surgery. The uptake site coincided with the convex part of each curve of the lumbar spine and was thought to be the result of the increased activity of paravertebral muscles due to their chronic stretched state in the kyphotic posture. This case report suggests the possibility of using (18)F-FDG PET/CT to visualize increased activity in paravertebral muscles and the ensuing pain in ASD patients. PMID- 27562568 TI - Sex-specific association between obesity and self-reported falls and injuries among community-dwelling Canadians aged 65 years and older. AB - : This study investigated the relationship between body mass index (BMI) and falls among community-dwelling elderly. Results indicate that obesity is associated with increased falls and there appears to be a sex-specific difference with obese men at higher risk of falling. Obesity is identified as a risk factor for falls in men. INTRODUCTION: The prevalence of falls, fall-related injuries, and obesity has increased over the last decade. The objectives of this study were to investigate sex-specific association and dose-response relationship between BMI and falls (and related injuries) among community-dwelling elderly. METHODS: Our study sample consisted of 15,860 adults aged 65 years or older (6399 men and 9461 women) from the 2008-2009 Canadian Community Health Survey-Healthy Aging (CCHS-HA). Falls, fall-related injuries, and BMI measures were self-reported. For both sex, dose-response curves presenting the relationship between BMI, falls, and fall-related injuries were first examined. Thereafter, multivariate logistic regression analyses were also performed to investigate these relationships after adjustment for potentially confounding variables. RESULTS: Of women, 21.7 % reported a fall and 16.9 % of men. The dose-response relationship between BMI and prevalence of falls showed that underweight and obese individuals reported falling more than normal and overweight individuals; this being more apparent in men than women. Finally, the dose relationship between BMI and prevalence of fall related injuries showed that only obese men seem more likely to have sustained a fall-related injury. Results from the multivariate analysis showed that obesity in men was significantly associated with higher odds of falling odds ratio (OR) 1.33 (1.04-1.70) and was not significantly associated with higher odds of fall related injuries OR 1.10 (0.66-1.84) over a 12-month period compared to normal weight men. For women, obesity was not significantly associated with higher fall prevalence OR 0.99 (0.79-1.25) and fall-related injuries OR 0.71 (0.51-1.00). CONCLUSION: Obesity is associated with self-reported falls, and there appears to be a sex-specific difference in elderly persons. PMID- 27562572 TI - New risks: the intended and unintended effects of mental health reform. AB - In crisis situations, the authority of the nurse is legitimised by legal powers and professional knowledge. Crisis stakeholders include those who directly use services and their families, and a wide range of health, social service and justice agencies. Alternative strategies such as therapeutic risk taking from the perspective of socially inclusive recovery policy coexist in a sometimes uneasy relationship with mental health legislation. A critical discourse analysis was undertaken to examine mental health policies and guidelines, and we interviewed service users, families, nurses and the police about experiences of accessing services. For those who attempt to access services early in crisis, as is suggested to lead to a better outcome, provision of services and rights appear to be reversed by an attempt to exclude them through practices that screen them out, rather than prioritising a choice in access. PMID- 27562571 TI - Early-life antibiotic use and subsequent diagnosis of food allergy and allergic diseases. AB - BACKGROUND: Antibiotic use in early life has been linked to disruptions in the microbiome. Such changes can disturb immune system development. Differences have been observed in the microbiota of children with and without allergies, but there have been few studies on antibiotic use and allergic disease. OBJECTIVE: We evaluated associations of early-life antibiotic use with subsequent occurrence of food allergy and other allergies in childhood using electronic health record data. METHODS: We used longitudinal data on 30 060 children up to age 7 years from Geisinger Clinic's electronic health record to conduct a sex- and age matched case-control study to evaluate the association between antibiotic use and milk allergy, non-milk food allergies, and other allergies. For each outcome, we estimated conditional logistic regression models adjusting for race/ethnicity, history of Medical Assistance, and mode of birth delivery. Models were repeated separately for penicillins, cephalosporins and macrolides. RESULTS: There were 484 milk allergy cases, 598 non-milk food allergy cases and 3652 other allergy cases. Children with three or more antibiotic orders had a greater odds of milk allergy (Odds Ratio; 95% Confidence interval) (1.78; 1.28-2.48), non-milk food allergy (1.65; 1.27-2.14), and other allergies (3.07; 2.72-3.46) compared with children with no antibiotic orders. Associations were strongest at younger ages and differed by antibiotic class. CONCLUSIONS AND CLINICAL RELEVANCE: We observed associations between antibiotic orders and allergic diseases, providing evidence of a potentially modifiable clinical practice associated with paediatric allergic disease. Differences by antibiotic class should be further explored, as this knowledge could inform paediatric treatment decisions. PMID- 27562573 TI - Political representation for social justice in nursing: lessons learned from participant research with destitute asylum seekers in the UK. AB - The concept of social justice is making a revival in nursing scholarship, in part in response to widening health inequalities and inequities in high-income countries. In particular, critical nurse scholars have sought to develop participatory research methods using peer researchers to represent the 'voice' of people who are living in marginalized spaces in society. The aim of this paper is to report on the experiences of nurse and peer researchers as part of a project to explore the experiences of people who find themselves destitute following the asylum process in the UK. In seeking to explore social injustice, three challenges are identified: lack of a robust political theory, institutional/professional constraints and an absence of skills to engage with the politics of social (in)justice. Each challenge is presented, opposing voices outlined and some possible solutions are suggested. The work of political theorist Nancy Fraser is used as a conceptual framework, in particular her focus on mis/framing and political representation for social justice. In addition, it is suggested that social justice needs to be further embedded in nursing policy and curriculum. Finally, nurses are encouraged to develop practical political skills to engage with both politics and the media in a neoliberal globalizing world. PMID- 27562574 TI - Gestational diabetes mellitus in Greenland: a national study of prevalence and testing efficacy. AB - BACKGROUND: Within the last 20 years, the prevalence of gestational diabetes mellitus (GDM) has been reported to be increasing worldwide in correlation with ethnic and geographic variations. The actual prevalence of GDM throughout all of Greenland remains unknown. OBJECTIVE: The aim of this study was to estimate the prevalence of GDM among Greenlanders and non-Greenlanders living in Greenland and to estimate the efficacy of testing for GDM. DESIGN: This study was performed as an observational, cross-sectional study including all women with permanent address in Greenland who had given birth to a singleton during 2014. The prevalence of GDM was calculated as the proportion of all pregnant women tested with a 75-g 2-h glucose tolerance test who had a 2-h capillary whole-blood glucose value of 8.5 mmol/l or above. Testing efficacy was calculated as the proportion of women who fulfilled the testing criteria who were actually tested in Greenland in 2014. RESULTS: A total of 794 women (727 Greenlanders and 67 non Greenlanders) were included in the study. The prevalence of GDM among tested women was 3.3% (confidence interval, CI: 0.9-5.6) among Greenlanders and 12.5% (CI: 0-25.7) among non-Greenlanders, corresponding, respectively, to 1.0% (CI: 0.3-1.3) and 4.5% (CI: 0-9.4) of all singleton pregnancies in Greenland in 2014. The overall testing efficacy was 69.0% among all eligible residents of Greenland and 85.1% among eligible residents in the capital city, Nuuk. CONCLUSION: In conclusion, the prevalence of GDM seems quite low in Greenland. Although diagnostic testing activity has improved within the last 6 years, still around one-third of all pregnant women in all Greenland fulfilling the testing criteria were not tested. Universal testing for GDM may be needed to improve testing of GDM in Greenland. PMID- 27562575 TI - Impact of insurance status on ability to return for outpatient management of pediatric supracondylar humerus fractures. AB - PURPOSE: Outcomes are excellent following surgical management of displaced supracondylar humerus fractures. Short delays until surgical fixation have been shown to be equivalent to immediate fixation with regards to complications. We hypothesized that insurance coverage may impact access to care and the patient's ability to return to the operating room for outpatient surgery. METHODS: A retrospective review of supracondylar humerus fractures treated at a large urban pediatric hospital from 2008 to 2012 was performed. Fractures were classified by the modified Gartland classification and baseline demographics were collected. Time from discharge to office visits and subsequent surgical fixation was calculated for all type II fractures discharged from the emergency department. Insurance status and primary carrier were collected for all patients. RESULTS: 2584 supracondylar humerus fractures were reviewed, of which 584 were type II fractures. Of the 577 type II fractures with complete records, 383 patients (61 %) were admitted for surgery and the remaining 194 were discharged with plans for outpatient follow-up. There was no difference in insurance status between patients admitted for immediate surgery. Of the 194 patients who were discharged with type 2 fractures after gentle reduction, 59 patients (30.4 %) ultimately underwent surgical fixation. Of these, 42 patients were privately insured (58.3 % of patients with private insurance), 16 had governmental insurance (15.1 %), and 1 was uninsured (6.3 %). Patients with private insurance were 2.46 times more likely to have surgery than patients with public or no insurance (p = 0.005). Of the 135 patients who did not eventually have surgery, 92 (68.1 %) were seen in the clinic. Patients with private insurance were 2.78 times more likely to be seen back in the clinic when compared to publicly insured or uninsured patients (p = 0.0152). CONCLUSIONS: Despite an equivalent number of privately insured and publicly insured patients undergoing immediate surgery for type II fractures, those with public or no insurance who were discharged were 2.46 times less likely to obtain outpatient surgery when compared to privately insured patients. Patient insurance status and the ability to follow up in a timely manner should be assessed at the time of initial evaluation in the emergency department. Level of evidence Level 3. PMID- 27562576 TI - Complications of banded laparoscopic Roux-en-Y gastric bypass in a 33-week pregnant woman. AB - Women desiring pregnancy might fail to conceive due to their obesity. Bariatric surgery has shown to reduce this infertility up to 58% and is therefore considered a successful strategy for morbidly obese infertile women. Nevertheless, when pregnancy has succeeded, surgery-related complications might occur.Banded laparoscopic Roux-en-Y gastric bypass (B-LRYGB) is a relatively new technique in which a band is placed around the small gastric pouch. We report a case of a 30-year-old woman who succeeded to become pregnant after weight loss due to B-LRYGB, but presented with acute abdominal pain in Week 33 of her pregnancy. PMID- 27562577 TI - Synchronous invasive ductal carcinoma in encapsulated papillary ductal carcinoma. AB - Encapsulated papillary ductal carcinoma (EPC) of the breast is a rare form of cancer with defining histopathology of encapsulation. These lesions are typically indolent but may rarely have concomitant, synchronous invasive lesions.This report details a 56-year-old black female who presented with a palpable left breast mass. Adenosis with focal fibrous and ductal hyperplasia characteristics were found on core needle biopsy. Excisional biopsy showed EPC with invasive components. A simple mastectomy was performed and a second lesion was identified as invasive ductal carcinoma.EPC typically has good prognosis and a low incidence of invasion. The risk increases in the presence of a second, synchronous lesion as in our case. Management is typically performed with breast conserving methods; however, missing a second lesion is possible. This report provides an overview of the literature and discussion of the role of MRI in preoperative workup. PMID- 27562578 TI - Ciliated muconodular papillary tumor of the lung: report of five cases. AB - We report five serial cases of ciliated muconodular papillary tumor (CMPT) of the lung. CMPT is characterized as a low-grade malignant tumor with ciliated columnar epithelial cells combined with goblet cells, typically presenting as peripheral lung tumor and often causing diagnostic or therapeutic problems. In the cases described here, all patients presented with abnormal chest shadow but no definitive symptoms. Although all tumors were peripheral, computed tomography (CT) revealed various radiographic findings including small lung nodules, ground grass opacity or irregular-shaped consolidation. All patients underwent complete surgical resection, and no recurrence has been noted over follow-up. In all cases, pathological findings included columnar ciliated cells with mucus lakes, consistent with the immunohistochemical staining. As there are few reports on this tumor entity, which has not yet received a WHO classification, we believe our case series may be of interest. PMID- 27562579 TI - The effect of urethral transection on erectile function after anterior urethroplasty. AB - PURPOSE: To prospectively assess the effect of urethral transection on erectile function after anterior urethroplasty. METHODS: From February 2012 to December 2014, 104 patients were enrolled in a prospective study assessing erectile function (EF) after anterior urethroplasty. Participants completed the International Index of Erectile Function (IIEF) questionnaire preoperatively and 6 months postoperatively. Outcome measures were the incidence of erectile dysfunction (ED) defined by >=5-point change in EF and mean change in the EF domain. Factors examined were urethral transection, stricture location, patient age and other demographics. Fisher's exact test, Student's t test and linear regression were used to evaluate associations when appropriate. RESULTS: Seventeen patients were excluded because of poor EF, leaving 87 patients for analysis. Twenty-two patients (25.3 %) had urethral transection during urethroplasty, while 65 underwent non-transecting techniques (74.7 %). For the entire cohort, IIEF scores remain unchanged (20.16 versus 20.14; p = 0.98). Eighteen patients (20.7 %) developed ED, while 15 (17.2 %) experienced an improvement in EF. Urethral transection was not associated with ED (p = 0.22) or mean change in EF (-0.8 versus +0.2; p = 0.71). Stricture location was not associated with ED, but patient age >=50 was associated with a decrease in mean postoperative EF (-2.84 versus +1.85; p = 0.04). On linear regression analysis patient age remained independently associated with adverse change in EF (p = 0.05). CONCLUSIONS: Urethroplasty can result in a decline in erectile function in some patients but overall is associated with minimal change in erectile function. Urethral transection is not associated with adverse change in erectile dysfunction after urethroplasty however, advanced patient age is. PMID- 27562580 TI - De novo formation of cerebral cavernous malformation adjacent to existing developmental venous anomaly - an effect of change in venous pressure associated with management of a complex dural arterio-venous fistula. AB - This is a case report of de novo development of two cerebral cavernous malformations adjacent to existing developmental venous anomalies. The development of cavernomas was noted over a follow-up period of 10 years. These developments happened during the course of staged endovascular management of a complex dural arterio-venous fistula along the right sphenoid wing. The patient presented with a proptosis secondary to lympho-haemangiomatous lesion of the fronto-orbital region and a high-flow right sphenoid wing dural arterio-venous fistula. During the initial period of conservative management of the dural arterio-venous fistula, he developed de novo cavernous malformations in the left mesial temporal lobe adjacent to a developmental venous anomaly in the temporal lobe, and along with this there was engorgement of deep veins related to another existing developmental venous anomaly in the brainstem. Later during the course of endovascular treatment of the dural arterio-venous fistula, a large brainstem cavernoma developed adjacent to the brainstem developmental venous anomaly. This case report discusses the cause-effect relationship of venous pressure changes related to management of dural arterio-venous fistula and de novo formation of cerebral cavernous malformations adjacent to existing developmental venous anomalies. PMID- 27562581 TI - Structural sex differences at disease onset in multiple sclerosis patients. AB - BACKGROUND: Male sex is associated with worsening disability and a more rapid progression of multiple sclerosis (MS). This study analysed structural sex differences in magnetic resonance images of the brain, comparing women whose disease started before and after the menopause with a control group of men. METHODS: This was a case control study in which female patients whose MS started before (Group 1) and after (Group 2) the menopause were included. The control group was matched by age, disease duration, Expanded Disability Status Scale and disease-modifying treatment. Patients were analysed according to demographic and clinical variables, as well as in terms of radiological measurements at disease onset and during the first 12 months of follow-up. These measurements included normalised total brain volume (NTBV), normalised cortical volume (NCV), normalised white matter volume, left and right hippocampus, the thalamus, brain stem volume, lesion load and percentage brain volume change. A linear regression model was used to analyse the data. RESULTS: A total of 97 patients were included: 53 in Group 1 (27 females) and 44 in Group 2 (22 females). In Group 1, we observed a reduction in brain volume in males compared with females at disease onset in NTBV (p = 0.01), NCV (p = 0.001) and brain stem volume (p = 0.01). We did not observe differences in Group 2 at disease onset in the brain volumes analysed. CONCLUSION: We observed structural sex differences in brain volume at disease onset in the pre-menopausal group. However, no structural differences were observed at disease onset between the sexes after the menopause had started. PMID- 27562582 TI - Assessment of diffusion tensor imaging metrics in differentiating low-grade from high-grade gliomas. AB - AIM: The aim of this article is to assess diffusion tensor imaging (DTI) metrics in differentiating low-grade from high-grade gliomas. PATIENTS AND METHODS: A prospective study was conducted on 35 patients with gliomas who underwent DTI. Gliomas were classified into low-grade and high-grade gliomas. The fractional anisotropy (FA), mean diffusivity (MD), linear coefficient (CL), planar coefficient (CP) and spherical coefficient (CS) of the solid tumoral part and peri-tumoral regions were calculated. RESULTS: There was significant difference (p = 0.001) in MD of the solid tumoral part of low-grade (1.78 +/- 0.33 * 10(-3 )mm(2)/s) and high-grade (1.16 +/- 0.22 * 10(-3 )mm(2)/s) gliomas. The selection of 1.42 * 10(-3 )mm(2)/s as a cutoff value of MD of the tumoral part was used to differentiate low-grade and high-grade gliomas; the best results were obtained with area under the curve (AUC) of 0.957 and accuracy of 91.4%. There was a significant difference in FA, MD, CP and CS of peri-tumoral regions of both groups with p values of 0.006, 0.042, 0.030 and 0.037, respectively. The cutoff values of MD, FA, CS and CP of the peri-tumoral region used to differentiate low grade from high-grade gliomas were 1.24, 0.315, 0.726 and 0.321 with AUC of 0.694, 0.773, 0.734 and 0.724 and accuracy of 68.6%, 80.0%, 74.3% and 74.3%, respectively. The combined MD of the solid tumoral part and FA of the peri tumoral region used to differentiate low-grade from high-grade gliomas revealed AUC of 0.974 and accuracy of 88.6%. CONCLUSION: We conclude that the combination of MD of the solid tumoral part and FA of the peri-tumoral region is a noninvasive method to differentiate low-grade from high-grade gliomas. PMID- 27562583 TI - Development of the Return-to-Work Obstacles and Self-Efficacy Scale (ROSES) and Validation with Workers Suffering from a Common Mental Disorder or Musculoskeletal Disorder. AB - Introduction Common mental disorders (CMDs) and musculoskeletal disorders (MSDs) lead the list of causes for work absence in several countries. Current research is starting to look at workers on sick leave as a single population, regardless of the nature of the disease or accident. The purpose of this study is to report the validation of the Return to Work Obstacles and Self-Efficacy Scale (ROSES) for people with MSDs and CMDs, based on the disability paradigm. Methods From a prospective design, the ROSES' reliability and validity were investigated in a Canadian sample of workers on sick leave due to MSDs (n = 206) and CMDs (n = 157). Results Exploratory and confirmatory factor analyses revealed that 46 items spread out on 10 conceptual dimensions (e.g., Fears of a relapse, Job demands, Difficult relation with the immediate supervisor), with satisfactory alpha coefficients and test-retest reliability for all subscales. Finally, several dimensions of ROSES also predict the participant's RTW within 6 months for MSDs (e.g., job demands), and CMDs (e.g., difficult relation with the immediate supervisor), even when adjusted by several variables (e.g., age, severity of symptoms). Apart from the job demands dimension, when the ROSES dimension is more external to the individual, only the perception of obstacles remains significant to predict RTW whereas it is the opposite result when the dimension is more internal (e.g., fears of a relapse). Conclusion The ROSES demonstrated satisfactory results regarding its validity and reliability with people having MSDs or CMDs, at the time of the return-to-work process. PMID- 27562585 TI - Descriptive epidemiology of breast cancer in China: incidence, mortality, survival and prevalence. AB - Breast cancer is the most common neoplasm diagnosed amongst women worldwide and is the leading cause of female cancer death. However, breast cancer in China is not comprehensively understood compared with Westernised countries, although the 5-year prevalence statistics indicate that approximately 11 % of worldwide breast cancer occurs in China and that the incidence has increased rapidly in recent decades. This paper reviews the descriptive epidemiology of Chinese breast cancer in terms of incidence, mortality, survival and prevalence, and explores relevant factors such as age of manifestation and geographic locations. The statistics are compared with data from the Westernised world with particular emphasis on the United States and Australia. Potential causal agents responsible for differences in breast cancer epidemiology between Chinese and other populations are also explored. The need to minimise variability and discrepancies in methods of data acquisition, analysis and presentation is highlighted. PMID- 27562584 TI - Employer Policies and Practices to Manage and Prevent Disability: Foreword to the Special Issue. AB - Purpose Employer policies and practices have been shown to impact workplace disability, but research in this area has waned in recent years despite an aging workforce, a growing prevalence of chronic health conditions, and a larger proportion of working-age adults on permanent work disability in many jurisdictions. The purpose of this article is to describe the background rationale and methodology for an invited conference designed to improve research of employer strategies to curtail work disability. Methods A multidisciplinary team of 26 international researchers with published research in employer-based disability management or related fields were invited to attend a 3-day conference in Hopkinton, Massachusetts, USA. The overall goal was to review the status of current research of workplace disability management and prevention, examine its relevance for employer decision-making, compare conceptual frameworks or theoretical perspectives, and recommend future research directions. Working groups were organized and draft manuscripts were prepared in advance. Conference activities included working group presentations and critiques, discussions with a panel of industry consultants and advisors, group interaction and debate, generation of final recommendations, and manuscript revision. Results/Conclusion Six principal domains were established with respect to future research: (a) further elucidation of the key workplace factors that buffer the disabling effects of injury and illness; (b) more innovative and feasible options for workplace intervention; (c) measurement of workplace-relevant disability outcomes; (d) a stronger theoretical framework for understanding the factors behind employer uptake and implementation; (e) a focus on special clinical populations and occupations where disability risk is most troubling; and (f) better representation of workers and employers that reflect the diverse and changing nature of work. Final comments and recommendations of the working groups are presented in the following six articles in this special issue of the Journal of Occupational Rehabilitation. Conference attendees recommended changes in methodology, collaboration strategies, and theoretical perspectives to improve the practical and scientific impact of future research of employer practices. PMID- 27562586 TI - In Vivo Gene Delivery to Lymph Node Stromal Cells Leads to Transgene-specific CD8+ T Cell Anergy in Mice. AB - Lymph node stromal cells play a role in self-tolerance by presenting tissue antigens to T cells. Yet, immunomodulatory properties of lymphoid tissue stroma, particularly toward CD4+ T cells, remain insufficiently characterized by lack of tools to target antigens for presentation by stromal cells. A lentiviral vector was therefore designed for antigen delivery to MHC class II+ cells of nonhematopoietic origin. Following intravenous vector delivery, the transgene was detected in lymph node gp38+ stromal cells which were CD45- MHCII+ and partly positive for CD86 and CTLA4 or B7-H4. The transgene was not detected in classical dendritic cells of lymph nodes or spleen. Transgene-specific CD4+ and CD8+ T cell responses were primed and regulatory T cells were also induced but effector T cell response did not develop, even after a peptide boost. Antigen-specific CD8+ T cells were not cytolytic in vivo. Thus, expressing a neo-antigen in MHC-II+ lymph node stroma seems to trigger blunt CD4 T cell responses leading to antigen specific CD8+ T cell anergy. These results open up new perspectives to further characterize lymph node stromal cell functional properties and to develop gene transfer protocols targeting lymph node stroma to induce peripheral tolerance. PMID- 27562587 TI - NFkappaB activation demarcates a subset of hepatocellular carcinoma patients for targeted therapy. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. It is a heterogeneous disorder and >80 % of the tumors develop in patients with liver cirrhosis, resulting from chronic inflammation and/or fibrosis. Here, we set out to identify novel targets for HCC therapy and to define a subgroup of patients that might benefit most from it. METHODS: Cellular pathway activation profiling of 45 transcription factors in a HCC-derived cell line (HEP3B), in vitro analysis of NFkappaB reporter activity in additional HCC-derived cell lines and pathway-focused integrative analyses of publicly available primary HCC-derived expression profiling data (GSE6764, GSE9843, E-TABM-36 and E-TABM-292) were employed to reveal a role of NFkappaB in HCC development. In order to identify potential targeting agents, a luciferase based NFkappaB reporter screening assay was established in HEP3B cells. After screening of a drug library through this assay, a potent NFkappaB pathway inhibitor was identified and characterized using an array of additional in vitro assays. RESULTS: Using cellular pathway activation profiling, we found a high activation of NFkappaB-mediated signaling in HCC-derived cell lines and in primary HCC tumors. Through NFkappaB inhibitor screening we observed a highly efficacious NFkappaB pathway inhibitory potential of ornithogalum in HCC-derived HEP3B cells. Although its active component still remains to be defined, ornithogalum has been found to inhibit endoplasmic reticulum (ER) and oxidative stress responses. ER stress, oxidative stress and NFkappaB signaling were found to be enhanced in a subset of HCCs, as well as in (precancerous) liver cirrhosis tissues. CONCLUSION: From our data we conclude that NFkappaB signaling is activated in precancerous cirrhosis tissues and in a subset of HCCs. We found that ornithogalum exhibits NFkappaB targeting and stress relieving activities. NFkappaB inhibitors, including the active component of ornithogalum, may serve as putative preventive and targeted therapeutic agents for at least a subset of HCCs in which the NFkappaB pathway is activated. These latter notions require further investigation in a translational context. PMID- 27562588 TI - Reducing intraoperative duration and ionising radiation exposure during the insertion of distal locking screws of intramedullary nails: a small-scale study comparing the current fluoroscopic method against radiation-free, electromagnetic navigation. AB - BACKGROUND: Intramedullary nailing is the standard surgical treatment for mid diaphyseal fractures of long bones; however, it is also a high radiation dose procedure. Distal locking is regularly cited as a demanding element of the procedure, and there remains a reliance on X-ray fluoroscopy to locate the distal holes. A recently developed electromagnetic navigation (EMN) system allows radiation-free distal locking, with a virtual on-screen image. OBJECTIVE: To compare operative duration, fluoroscopy time and radiation dose when using EMN over fluoroscopy, for the distal locking of intramedullary nails. METHOD: Consecutive patients with mid-diaphyseal fractures of the tibia and femur, treatable with intramedullary nails, were prospectively enrolled during a 9-month period. The sample consisted of 29 individuals, 19 under fluoroscopic guidance and 10 utilising EMN. Participants were allocated depending on the type of intramedullary nail used and surgeon's preference. These were further divided into tibial and femoral subcategories, relative to the fracture site. RESULTS: EMN reduced fluoroscopy time by 49 (p = 0.038) and 28 s during tibial and femoral nailings, respectively. Radiation dose was reduced by 18 cGy/cm2 (p = 0.046) during tibial and 181 cGy/cm2 during femoral nailings when utilising EMN. Operative duration was 11 min slower during tibial nailings using EMN, but 38 min faster in respect of femoral nailings. CONCLUSIONS: This study has evidenced statistically significant reductions in both fluoroscopy time and radiation dose when using EMN for the distal locking of intramedullary nails. It is expected that overall operative duration would also decrease in line with similar studies, with increased usage and a larger sample. PMID- 27562589 TI - Sagittal balance parameters correlate with spinal conformational type and MRI changes in lumbar degenerative disc disease: results of a retrospective study. AB - PURPOSE: Spinopelvic parameters can be useful in identifying risk factors for lumbar degenerative disc disease, but few studies assess patients with single level disc herniation and most do not evaluate symptoms. This comparative retrospective study was aimed to analyse spinopelvic parameters, symptoms and MRI changes in patients with single-level lumbar disc herniation undergoing conservative or surgical treatment. METHODS: Patients with clinical and radiological assessment (Japanese Orthopaedic Association Score) and an MRI evaluation of the lumbar spine were identified and divided into two groups: surgically treated (group A) and not requiring surgery (group B). Spinopelvic parameters were determined on standing profile radiographs of the lumbar spine and pelvis, and mean values were compared to those reported in the literature for normal subjects. MRI findings were graded according to the system described by Pfirrmann et al. RESULTS: The study included 71 patients with single-level lumbar disc herniation: 26 in group A (39.4 +/- 12.1 years) and 45 in group B (51.4 +/- 17.2 years). The notable differences in spinopelvic parameter means between the two groups did not reach statistical significance. A positive correlations of age with pelvic tilt and Pfirrmann changes with pelvic incidence was only found in group A, while both groups showed highly significant positive correlations of pelvic incidence with the spine's conformational type (p = 0.001). CONCLUSIONS: Characteristic changes in spinopelvic parameters identified in patients with lumbar degenerative disc disease were a reduction in pelvic incidence, sacral slope and lumbar lordosis, with an increased pelvic tilt. These were found to correlate with MRI changes in surgically treated patients. PMID- 27562590 TI - Posterior shoulder fracture-dislocation: an update with treatment algorithm. AB - Posterior shoulder fracture-dislocation is a rare injury accounting for approximately 0.9 % of shoulder fracture-dislocations. Impression fractures of the articular surface of the humeral head, followed by humeral neck fractures and fractures of the lesser and grater tuberosity, are the more common associated fractures. Multiple mechanisms have been implicated in the etiology of this traumatic entity most commonly resulting from forced muscle contraction as in epileptic seizures, electric shock or electroconvulsive therapy, major trauma such as motor vehicle accidents or other injuries involving axial loading of the arm, in an adducted, flexed and internally rotated position. Despite its' scarce appearance in daily clinical practice, posterior shoulder dislocation is of significant diagnostic and therapeutic interest because of its predilection for age groups of high functional demands (35-55 years old), in addition to high incidence of missed initial diagnosis ranging up to 79 % in some studies. Several treatment options have also been proposed to address this type of injury, ranging from non-surgical methods to humeral head reconstruction procedures or arthroplasty with no clear consensus over definitive treatment guidelines, reflecting the complexity of this injury in addition to the limited evidence provided by the literature. To enhance the literature, this article aims to present the current concepts for the diagnosis, evaluation and treatment of the patients with posterior fracture-dislocation shoulder, and to present a treatment algorithm based on the literature review and our own experience. PMID- 27562591 TI - Propensity for Japanese-American older adults' use of medical alert services in Hawaii. AB - AIM: Hawaii is a fast-aging, multi-ethnic state. At present, ethnic Japanese represent the largest segment of the elderly population (aged >=65 years). Studies in Western countries have identified an association between ethnicity and the use of homecare services. The present study sought to substantiate this association in relation to the use of a personal emergency response system service by older ethnic Japanese adults in Hawaii. METHODS: Questionnaires were mailed to 585 elderly subscribers of a company providing personal emergency response system services in Hawaii in 2014. The questionnaire inquired about the subscriber's ethnicity, functional disability, number of medications taken and falls experienced. Additional information on the sex, age and service payer was obtained for each of the responding subscribers from the corporate database. The chi2 -test and t-test were carried out to assess the associations between factors. RESULTS: A total of 244 questionnaires were analyzed (41.7% response rate; mean age of respondents 86.1 + 7.8 years). Compared with non-Japanese older adults, ethnic Japanese older adults had a higher propensity to use the personal emergency response system services, were older, used fewer prescribed medications and were more likely to have these services paid for by family members or to pay themselves. CONCLUSIONS: Japanese culture might influence the use of personal emergency response system services. Ethnic Japanese older adults might want to receive homecare services focusing on preventing minor accidents from becoming medical crises because of their high level of concern for health, their independence and the availability of family support. Healthcare planners should consider such factors in the provision of care in Hawaii. Geriatr Gerontol Int 2017; 17: 1392-1398. PMID- 27562592 TI - Comparison of microbial communities during the anaerobic digestion of Gracilaria under mesophilic and thermophilic conditions. AB - Mesophilic and thermophilic anaerobic digesters (MD and TD, respectively) utilizing Gracilaria and marine sediment as the substrate and inoculum, respectively, were compared by analyzing their performances and microbial community changes. During three successive transfers, the average cumulative methane yields in the MD and TD were 222.6 +/- 17.3 mL CH4/g volatile solids (VS) and 246.1 +/- 11 mL CH4/g VS, respectively. The higher hydrolysis rate and acidogenesis in the TD resulted in a several fold greater accumulation of volatile fatty acids (acetate, propionate, and butyrate) followed by a larger pH drop with a prolonged recovery than in the MD. However, the operational stability between both digesters remained comparable. Pyrosequencing analyses revealed that the MD had more complex microbial diversity indices and microbial community changes than the TD. Interestingly, Methanomassiliicoccales, the seventh methanogen order was the predominant archaeal order in the MD along with bacterial orders of Clostridiales, Bacteriodales, and Synergistales. Meanwhile, Coprothermobacter and Methanobacteriales dominated the bacterial and archaeal community in the TD, respectively. Although the methane yield is comparable, both MD and TD show a different profile of pH, VFA and the microbial communities. PMID- 27562593 TI - Bacillus aryabhattai BA03: a novel approach to the production of natural value added compounds. AB - A strain designated as BA03, with the ability to transform ferulic acid into vanillin and 4-vinylguaiacol, was isolated from contaminated cryovials. The production of natural value-added compounds was dependent on the media employed. The morphological and physiological characteristics of this strain were compared with those of the typical vanillin-producer strain Amycolatopsis sp. ATCC 39116. According to a partial 16S rRNA sequence, we determined that BA03 belonged to Bacillus aryabhattai. In addition, analysis of the results showed that this strain exhibited interesting enzymatic activity, including cellulases, laccases, lipases and pectinases. In light of this, we propose new functions for this multitasking microorganism. We suggest that it may be used for converting lignocellulosic wastes into byproducts with industrial uses, and also for treating disposal residues such as dyes in the textile industry. Hence, the possibility for novel research with B. aryabhattai opens up in the fields of biodegradation and/or revalorization of wastes. PMID- 27562594 TI - Effect of red and blue light emitting diodes "CRB-LED" on in vitro organogenesis of date palm (Phoenix dactylifera L.) cv. Alshakr. AB - The objective of the present study is to determine the effect of light source on enhancement of shoot multiplication, phytochemicals, as well as, antioxidant enzyme activities of in vitro cultures of date palm cv. Alshakr. In vitro-grown buds were cultured on Murashige and Skoog (MS) medium and incubated under a conventional white fluorescent light (control), and combinations of red + blue light emitting diode (18:2) (CRB-LED). Results revealed that the treatment of CRB LED showed a significant increase in the number of shoots compared with the white florescent light. Total soluble carbohydrate "TSCH" (7.10 mg g(-1) DW.), starch (1.63 mg g(-1) DW.) and free amino acids (2.90 mg g(-1) DW.) were significantly higher in CRB-LED (p < 0.05). Additionally, CRB-LED induced a higher peroxidase activity (25.50 U ml(-1)) compared with the white fluorescent light treatment (19.74 U ml(-1)) as control treatment. Potassium, magnesium and sodium contents in (3.62, 13.99 and 2.76 mg g(-1) DW.) were increased in in vitro shoots under CRB-LED treatment in comparison with fluorescent light (p < 0.05). Protein profile showed the appearance of newly bands with the molecular weight of 38 and 60 kDa at the treatment CRB-LED compared with control treatment. Our results demonstrate the positive effects of CRB-LED light during the course of date palm tissue cultures. PMID- 27562595 TI - Terpenoid bioactive compound from Streptomyces rochei (M32): taxonomy, fermentation and biological activities. AB - The present study emphasized the production of biologically active terpenoid compound from Streptomyces rochei M32, which was isolated from Western Ghats ecosystem, South India. The presence of resistant genes like mecA, vanA of Staphylococcus aureus and bla SHV, bla TEM of Pseudomonas aeruginosa was confirmed by molecular studies. The isolated compound from Streptomyces rochei M32 inhibited wide range of standard and clinical drug resistant pathogens and enteric pathogens. The rice bran supplemented basal medium influenced the active compound production on 8th day of fermentation and yielded 1875 mg of crude extract from 10 g of rice bran substrate. Purification and characterization of crude ethyl acetate extract was achieved by preparative thin layer chromatography. The active fraction was identified as terpenoid class compound by chemical screening. Based on the results of spectral studies (NMR, LC-MS, FTIR, etc.), the active compound was tentatively identified as 1, 19-bis (3 hydroxyazetidin-1-yl) nonadeca-5, 14-diene-1, 8, 12, 19-tetraone with molecular weight 462.41 g/mol. Minimum inhibitory concentration value ranges between 7.6 and 31.2 ug/mL against test organisms was observed. The cytotoxicity results on cervical cancer (HeLa) cell line showed IC50 value of 2.034 ug/mL. The corresponding compound is not previously reported from any microbial resources. PMID- 27562596 TI - Characterization of Staphylococcus aureus isolates from pediatric patients with cystic fibrosis. AB - Staphylococcus aureus is one of the major respiratory pathogens associated with cystic fibrosis (CF) patients. In this study, we collected sputum and isolated fifty S. aureus isolates from CF patients with the median age of 9.5 years old. Then we determined the profiles of these isolates by antibiotic susceptibility testing, examining their cytotoxicity and ability to internalize into an epithelial cell line (A549), as well as multiple loci sequencing typing. Predominant CF S. aureus isolates were resistant to penicillin; however, these isolates were sensitive to various antibiotics, such as vancomycin and minocycline. Different CF S. aureus isolates showed distinct cytotoxic activities, and 90 % of CF S. aureus isolates possessed the enterotoxin genes, sea and hlg. Moreover, we found that multiple different CF S. aureus isolates appeared to have the distinct capacity of invading A549 cells. ST5 (14 %), ST30 (14 %), and ST8 (10 %) were prevalent ST types in these isolates. Further analysis revealed that ST5 and ST30 isolates were less toxic than ST8 and ST15 isolates, and that the ST5, ST15, ST59, and ST87 types of CF S. aureus were less capable of invading A549 cells. Our results suggest that the ST typing method may be useful in predicting cytotoxicity and the invading capacity of S. aureus isolates from patients with CF. PMID- 27562597 TI - Aurintricarboxylic acid structure modifications lead to reduction of inhibitory properties against virulence factor YopH and higher cytotoxicity. AB - Yersinia sp. bacteria owe their viability and pathogenic virulence to the YopH factor, which is a highly active bacterial protein tyrosine phosphatase. Inhibition of YopH phosphatase results in the lack of Yersinia sp. pathogenicity. We have previously described that aurintricarboxylic acid inhibits the activity of YopH at nanomolar concentrations and represents a unique mechanism of YopH inactivation due to a redox process. This work is a continuation of our previous studies. Here we show that modifications of the structure of aurintricarboxylic acid reduce the ability to inactivate YopH and lead to higher cytotoxicity. In the present paper we examine the inhibitory properties of aurintricarboxylic acid analogues, such as eriochrome cyanine R (ECR) and pararosaniline. Computational docking studies we report here indicate that ATA analogues are not precluded to bind in the YopH active site and in all obtained binding conformations ECR and pararosaniline bind to YopH active site. The free binding energy calculations show that ECR has a stronger binding affinity to YopH than pararosaniline, which was confirmed by experimental YopH enzymatic activity studies. We found that ATA analogues can reversibly reduce the enzymatic activity of YopH, but possess weaker inhibitory properties than ATA. The ATA analogues induced inactivation of YopH is probably due to oxidative mechanism, as pretreatment with catalase prevents from inhibition. We also found that ATA analogues significantly decrease the viability of macrophage cells, especially pararosaniline, while ATA reveals only slight effect on cell viability. PMID- 27562598 TI - Acorus calamus Linn.: phytoconstituents and bactericidal property. AB - Acorus calamus Linn. of the family Araceae (Acoraceae), commonly known as Sweet Flag and Vacha. The rhizome of this plant has medicinal properties against bugs, moths, lice and emetic stomach in dyspepsia. Chemical composition of the hydro distilled essential oil obtained from the rhizomes of A. calamus was analyzed by gas chromatography equipped with flame ionization detector and gas chromatography coupled with mass spectrometry. The essential oil of A. calamus and its major compound beta-asarone were tested against five Gram-positive, eight Gram-negative bacteria, and three fungi by the tube-dilution method at a concentration rang of 5.0-0.009 mg/mL. Forty constituents were identified which comprised 98.3 % of the total oil. The major compound beta-asarone (80.6 %) was identified and confirm by NMR ((1)H- & (13)C-) in rhizome oil of A. calamus. The organism Micrococcus luteus was found to be more susceptible to the oil with minimum bactericidal concentration (MBC) value of 0.032 +/- 0.004 mg/mL, followed by Aspergillus fumigatus, Aspergillus niger and Micrococcus flavus with MBC values of 0.104 +/- 0.016, 0.117 +/- 0.017 and 0.143 +/- 0.013 mg/mL, respectively. The compound beta asarone was susceptible to the microorganism A. niger with MBC value 0.416 +/- 0.065 mg/mL. The present study revealed that tetraploid variety of A. calamus is growing in this region with substantial amount of beta-asarone. The oil showed bactericidal property against tested bacteria and fungi. The beta-asarone exhibited poorer bactericidal activity against test microorganisms. PMID- 27562599 TI - The feather-degrading bacterial community in two soils as revealed by a specific primer targeting serine-type keratinolytic proteases. AB - Feather waste represents a huge resource of protein, but is underutilized due to its recalcitrant nature. Feather-degrading bacteria can biologically degrade feathers and have great potential for industries. In this study, we first designed a primer set (BC) suitable for exploring the diversity of the keratinolytic bacterial community with denatured gradient gel electrophoresis (DGGE). With the BC primer set, the difference in the keratinolytic bacterial community between a feather-dumping (FD) soil and a non feather-dumping (NFD) soil and the influence of feather addition (enrichment culture) on the keratinolytic bacterial community were investigated. DGGE and sequencing showed that keratinolytic bacteria in these soils belong to 2 phyla (Actinobacteria and Proteobacteria) and 9 genera (Micromonospora, Verrucosispora, Actinopolymorpha, Knoellia, Hyalangium, Stigmatella, Archangium, Cystobacter, and Luteimonas). Feather addition decreased the species richness of the keratinolytic bacteria in FD soil, but greatly increased the diversity, species richness and abundance in NFD soil. Moreover, feather addition to NFD soil induced some keratinolytic bacteria that were absent in all of the other soils. Collectively, these data indicate that keratinolytic bacteria are diverse in both FD and NFD soil, and some novel keratinolytic bacteria taxa might be revealed by using the BC primer set. PMID- 27562600 TI - RNAi-mediated silencing of TNF-alpha converting enzyme to down-regulate soluble TNF-alpha production for treatment of acute and chronic colitis. AB - Elevated level of tumor necrosis factor-alpha (TNF-alpha), one of the inflammatory cytokines, is considered to be a potential target for the inflammatory bowel disease (IBD) therapy. Recently, TNF-alpha converting enzyme (TACE), a sheddase playing an important role in cleaving and releasing bioactive soluble TNF-alpha, has been challenged with inhibitors to treat inflammatory diseases. Here, we report a novel anti-TNF-alpha strategy using a short hairpin RNA silencing TACE (shTACE) to prevent and treat colitis. The shTACE formed stable complexes with nona-arginine-based bio-cleavable disulfide bond-linked poly (arginine) (PAs-s) for enhanced gene delivery. Systemically administered shTACE/PAs-s peptoplexes efficiently decreased TNF-alpha levels, increased survival and alleviated pathophysiological parameters representing colitis severity. Our results demonstrate effectiveness and safety of shTACE/PAs-s peptoplexes with the capacity of overcoming acute and chronic ulcerative colitis through modulation of excessive inflammatory responses in the colon, providing a strong potential as a therapeutic agent for a broad variety of inflammatory diseases. PMID- 27562603 TI - Quantifying antiepileptic drug effects using intrinsic excitability measures. AB - Pathologic increases in excitability levels of cortical tissue commonly underlie the initiation and spread of seizure activity in patients with epilepsy. By reducing the excitability levels in neural tissue, antiepileptic drug (AED) pharmacotherapy aims to reduce seizure severity and frequency. However, AEDs may also bring about adverse effects, which have been reported to increase with higher AED load. Measures that monitor the dose-dependent effects of AEDs on cortical tissue and quantify its excitability level are therefore of prime importance for efficient clinical care and treatment but have been difficult to identify. Here, we systematically analyze continuous multiday electrocorticography (ECoG) data from 10 patients under different levels of AED load and derive the recently proposed intrinsic excitability measures (IEMs) from different brain regions and across different frequency bands. We find that IEMs are significantly negatively correlated with AED load (prescribed daily dose/defined daily dose). Furthermore, we demonstrate that IEMs derived from different brain regions can robustly capture global changes in the degree of excitability. These results provide a step toward the ultimate goal of developing a reliable quantitative measure of central physiologic effects of AEDs in patients with epilepsy. PMID- 27562602 TI - Structure-function relationship of the mammarenavirus envelope glycoprotein. AB - Mammarenaviruses, including lethal pathogens such as Lassa virus and Junin virus, can cause severe hemorrhagic fever in humans. Entry is a key step for virus infection, which starts with binding of the envelope glycoprotein (GP) to receptors on target cells and subsequent fusion of the virus with target cell membranes. The GP precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite GP complex (GPC) formed by a stable signal peptide (SSP), GP1 and GP2. The unique retained SSP interacts with GP2 and plays essential roles in virion maturation and infectivity. GP1 is responsible for binding to the cell receptor, and GP2 is a class I fusion protein. The native structure of the tripartite GPC is unknown. GPC is critical for the receptor binding, membrane fusion and neutralization antibody recognition. Elucidating the molecular mechanisms underlining the structure function relationship of the three subunits is the key for understanding their function and can facilitate novel avenues for combating virus infections. This review summarizes the basic aspects and recent research of the structure-function relationship of the three subunits. We discuss the structural basis of the receptor-binding domain in GP1, the interaction between SSP and GP2 and its role in virion maturation and membrane fusion, as well as the mechanism by which glycosylation stabilizes the GPC structure and facilitates immune evasion. Understanding the molecular mechanisms involved in these aspects will contribute to the development of novel vaccines and treatment strategies against mammarenaviruses infection. PMID- 27562604 TI - On the effectiveness of multilevel selection. AB - Experimental studies of group selection show that higher levels of selection act on indirect genetic effects, making the response to group and community selection qualitatively different from that of individual selection. This suggests that multilevel selection plays a key role in the evolution of supersocial societies. Experiments showing the effectiveness of community selection indicate that we should consider the possibility that selection among communities may be important in the evolution of supersocial species. PMID- 27562601 TI - ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules. AB - Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation. In this report, we show that ASPM may control spindle positioning by interacting with citron kinase (CITK), a protein whose loss is also responsible for severe microcephaly in mammals. We show that the absence of CITK leads to abnormal spindle orientation in mammals and insects. In mouse cortical development, this phenotype correlates with increased production of basal progenitors. ASPM is required to recruit CITK at the spindle, and CITK overexpression rescues ASPM phenotype. ASPM and CITK affect the organization of astral microtubules (MT), and low doses of MT stabilizing drug revert the spindle orientation phenotype produced by their knockdown. Finally, CITK regulates both astral-MT nucleation and stability. Our results provide a functional link between two established microcephaly proteins. PMID- 27562605 TI - Thermal limits of leaf metabolism across biomes. AB - High-temperature tolerance in plants is important in a warming world, with extreme heat waves predicted to increase in frequency and duration, potentially leading to lethal heating of leaves. Global patterns of high-temperature tolerance are documented in animals, but generally not in plants, limiting our ability to assess risks associated with climate warming. To assess whether there are global patterns in high-temperature tolerance of leaf metabolism, we quantified Tcrit (high temperature where minimal chlorophyll a fluorescence rises rapidly and thus photosystem II is disrupted) and Tmax (temperature where leaf respiration in darkness is maximal, beyond which respiratory function rapidly declines) in upper canopy leaves of 218 plant species spanning seven biomes. Mean site-based Tcrit values ranged from 41.5 degrees C in the Alaskan arctic to 50.8 degrees C in lowland tropical rainforests of Peruvian Amazon. For Tmax , the equivalent values were 51.0 and 60.6 degrees C in the Arctic and Amazon, respectively. Tcrit and Tmax followed similar biogeographic patterns, increasing linearly (~8 degrees C) from polar to equatorial regions. Such increases in high temperature tolerance are much less than expected based on the 20 degrees C span in high-temperature extremes across the globe. Moreover, with only modest high temperature tolerance despite high summer temperature extremes, species in mid latitude (~20-50 degrees ) regions have the narrowest thermal safety margins in upper canopy leaves; these regions are at the greatest risk of damage due to extreme heat-wave events, especially under conditions when leaf temperatures are further elevated by a lack of transpirational cooling. Using predicted heat-wave events for 2050 and accounting for possible thermal acclimation of Tcrit and Tmax , we also found that these safety margins could shrink in a warmer world, as rising temperatures are likely to exceed thermal tolerance limits. Thus, increasing numbers of species in many biomes may be at risk as heat-wave events become more severe with climate change. PMID- 27562606 TI - Developing competence and confidence in midwifery-focus groups with Swedish midwives. AB - BACKGROUND: Midwives have a significant impact on the clinical outcome and the birthing experience of women. However, there has been a lack of research focusing specifically on clinical midwives' learning and development of professional competence. AIM: The objective of the study was to describe how midwives reflect on learning and the development of professional competence and confidence. METHODS: A qualitative study based on focus groups with midwives employed in maternity services. FINDINGS: Four categories describe the results: (1) Feelings of professional safety evolve over time; (2) Personal qualities affect professional development; (3) Methods for expanding knowledge and competence; and (4) Competence as developing and demanding. The meaning of competence is to feel safe and secure in their professional role. There was a link between the amount of hands-on intrapartum experience and increasing confidence that is, assisting many births made midwives feel confident. Internal rotation was disliked because the midwives felt they had less time to deepen their knowledge and develop competence in a particular field. The midwives felt they were not seen as individuals, and this system made them feel split between different assignments. DISCUSSION: External factors that contribute to the development of knowledge and competence include the ability to practise hands-on skills in an organisation that is supportive and non-threatening. Internal factors include confidence, self efficacy, and a curiosity for learning. CONCLUSIONS: Midwives working within an organisation should be supported to develop their professional role in order to become knowledgeable, competent and confident. PMID- 27562607 TI - Linguistic representations and memory architectures: The devil is in the details. AB - Attempts to explain linguistic phenomena as consequences of memory constraints require detailed specification of linguistic representations and memory architectures alike. We discuss examples of supposed locality biases in language comprehension and production, and their link to memory constraints. Findings do not generally favor Christiansen & Chater's (C&C's) approach. We discuss connections to debates that stretch back to the nineteenth century. PMID- 27562608 TI - Development of Dipeptidic hGPR54 Agonists. AB - A series of dipeptides were designed as potential agonists of the human KiSS1 derived peptide receptor (hGPR54). While the sequence Arg-Trp-NH2 was the most efficient in terms of affinity, we established a convergent synthetic strategy to optimize the N terminus. Using two successive Sonogashira cross-coupling reactions on a solid-supported peptide, we were able to introduce various alkynes at the N terminus to afford compounds with sub-micromolar affinities for hGPR54. However, functional assays indicated the benzoylated dipeptide Bz-Arg-Trp-NH2 as the most promising compound in terms of agonistic properties. Interestingly, this compound appeared much more stable than the endogenous neuropeptide kisspeptin, both in serum and in liver microsomes of rats. This compound was also found to be able to induce a significant in vivo increase in testosterone levels in male rats. PMID- 27562609 TI - Functional hyaluronate collagen scaffolds induce NSCs differentiation into functional neurons in repairing the traumatic brain injury. AB - : The traumatic brain injury (TBI) usually causes brain tissue defects, including neuronal death or loss, which ultimately results in dysfunction in some degree. The cell replacement therapy is now one of the most promising methods for such injury. There are currently various methods to induce the differentiation of stem cells into neurons, but all extremely complex, slow and unstable. Here we report that the sodium hyaluronate collagen scaffold loaded with bFGF (bFGF-controlled releasing system, bFGF-CRS) can induce neural stem cells (NSCs) to differentiate into multi-type and mature functional neurons at a high percentage of 82+/-1.528% in two weeks. The quantitative real-time (QRT) PCR results reveal that a long term activation of bFGF receptors could up-regulate ERK/MAPK signal pathways, thus facilitating the formation of presynaptic and postsynaptic structure among the induced neuronal cells (iN cells). The functional synaptic connections established among iN cells were detected by the planar multielectrode dish system. When jointly transplanting the bFGF-CRS and NSCs into the CA1 zone of the rat TBI area, the results suggested that bFGF-CRS provided an optimal microenvironment, which promoted survival, neuronal differentiation of transplanted NSCs and functional synapse formation not only among iN cells but also between iN cells and the host brain tissue in TBI rats, consequently leading to the cognitive function recovery of TBI rats. These findings in vitro and in vivo may lay a foundation for the application of bFGF-CRS and shed light on the delivery of exogenous cells or nutrients to the CNS injury or disease area. STATEMENT OF SIGNIFICANCE: A sodium hyaluronate collagen scaffold was specifically functionalized with nutrient-bFGF which can induce the differentiation of neural stem cells (NSCs) into multi-type and mature functional neurons at a high percentage in two week. When jointly transplanting the bFGF-CRS and NSCs into the CA1 zone of the traumatic brain injured area of adult rats, the bFGF-CRS could provide an optimal microenvironment, which promoted survival, migration and neuronal differentiation of transplanted NSCs and functional synapse formation among iN cells, as well as between iN cells and host brain tissue in TBI rats, consequently leading to the cognitive function recovery of TBI rats. PMID- 27562610 TI - Cell sheet mechanics: How geometrical constraints induce the detachment of cell sheets from concave surfaces. AB - : Despite of the progress made to engineer structured microtissues such as BioMEMS and 3D bioprinting, little control exists how microtissues transform as they mature, as the misbalance between cell-generated forces and the strength of cell-cell and cell-substrate contacts can result in unintended tissue deformations and ruptures. To develop a quantitative perspective on how cellular contractility, scaffold curvature and cell-substrate adhesion control such rupture processes, human aortic smooth muscle cells were grown on glass substrates with submillimeter semichannels. We quantified cell sheet detachment from 3D confocal image stacks as a function of channel curvature and cell sheet tension by adding different amounts of Blebbistatin and TGF-beta to inhibit or enhance cell contractility, respectively. We found that both higher curvature and higher contractility increased the detachment probability. Variations of the adhesive strength of the protein coating on the substrate revealed that the rupture plane was localized along the substrate-extracellular matrix interface for non-covalently adsorbed adhesion proteins, while the collagen-integrin interface ruptured when collagen I was covalently crosslinked to the substrate. Finally, a simple mechanical model is introduced that quantitatively explains how the tuning of substrate curvature, cell sheet contractility and adhesive strength can be used as tunable parameters as summarized in a first semi-quantitative phase diagram. These parameters can thus be exploited to either inhibit or purposefully induce a collective detachment of sheet-like microtissues for the use in tissue engineering and regenerative therapies. STATEMENT OF SIGNIFICANCE: Despite of the significant progress in 3D tissue fabrication technologies at the microscale, there is still no quantitative model that can predict if cells seeded on a 3D structure maintain the imposed geometry while they form a continuous microtissue. Especially, detachment or loss of shape control of growing tissue is a major concern when designing 3D-structured scaffolds. Utilizing semi cylindrical channels and vascular smooth muscle cells, we characterized how geometrical and mechanical parameters such as curvature of the substrate, cellular contractility, or protein-substrate adhesion strength tune the catastrophic detachment of microtissue. Observed results were rationalized by a theoretical model. The phase diagram showing how unintended tissue detachment progresses would help in designing of mechanically-balanced 3D scaffolds in future tissue engineering applications. PMID- 27562611 TI - Binder-jetting 3D printing and alloy development of new biodegradable Fe-Mn-Ca/Mg alloys. AB - : 3D printing of various biomaterials including titanium and stainless steel has been studied for treating patients with cranio-maxillofacial bone defect. The potential long term complications with use of inert biometals have opened the opportunities for use of biodegradable metals in the clinical arena. The authors previously reported that binder-jet 3D printing technique enhanced the degradation rates of biodegradable Fe-Mn alloy by creating engineered micropores rendering the system attractive as biodegradable implantable devices. In the present study, the authors employed CALPHAD modeling to systematically study and modify the Fe-Mn alloy composition to achieve enhanced degradation rates. Accordingly, Ca and Mg addition to Fe-35wt% Mn solid solution predicted increase in degradation rates. In order to validate the CALPHAD results, Fe - (35-y)wt% Mn - ywt% X (X=Ca, Mg, and y=0, 1, 2) were synthesized by using high energy mechanical alloying (HEMA). Sintered pellets of Fe-Mn-Ca and Fe-Mn-Mg were then subjected to potentiodynamic polarization (PDP) and live/dead cell viability tests. Sintered pellets of Fe-Mn, Fe-Mn-Ca, and Fe-Mn-Mg also exhibited MC3T3 murine pre-osteoblast cells viability in the live/dead assay results. Fe-Mn and Fe-Mn-1Ca were thus accordingly selected for 3D printing and the results further confirmed enhanced degradation of Ca addition to 3D printed constructs validating the theoretical and alloy development studies. Live/dead and MTT cell viability results also confirmed good cytocompatibility of the 3D-printed Fe-Mn and Fe-Mn 1Ca constructs. STATEMENT OF SIGNIFICANCE: Bone grafting is widely used for the treatment of cranio-maxillofacial bone injuries. 3D printing of biodegradable Fe alloy is anticipated to be advantageous over current bone grafting techniques. 3D printing offers the fabrication of precise and tailored bone grafts to fit the patient specific bone defect needs. Biodegradable Fe alloy is a good candidate for 3D printing synthetic grafts to regenerate bone tissue without eliciting complications. CALPHAD theoretical models were used to develop new Fe-Mn-Ca/Mg alloys to enhance the degradation rates of traditional Fe-Mn alloys. In vitro experimental results also showed enhanced degradation rates and good cytocompatibility of sintered Fe-Mn-Ca/Mg compacts. 3D printing of Fe-Mn and Fe Mn-1Ca alloys further demonstrated their feasibility as potentially viable bone grafts for the future. PMID- 27562612 TI - Societal threat as a moderator of cultural group selection. AB - As scholars have rushed to either prove or refute cultural group selection (CGS), the debate lacks sufficient consideration of CGS's potential moderators. We argue that pressures for CGS are particularly strong when groups face ecological and human-made threat. Field, experimental, computational, and genetic evidence are presented to substantiate this claim. PMID- 27562613 TI - Mean telomere length is not associated with current health status in a 50-year old population sample. AB - OBJECTIVES: Telomeres are nucleoprotein complexes that cap the ends of linear chromosomes. Telomeric DNA decreases with age and shows considerable heterogeneity in the wider population. There is interest in the application of telomere length measures as a biomarker of general health or "biological age," and the possibility of using mean telomere length to gauge individual disease risk, and to promote lifestyle changes to improve health. This study examined the effectiveness of telomere length as a biomarker for an individual's current overall health status by assessing several measures of general health including SF-36v2 score, current smoking status and a comprehensive obesity phenotype. METHODS: Participants were from the Canterbury Health, Ageing and Lifecourse (CHALICE) cohort, a New Zealand population based multidisciplinary study of aging. Telomere length measurements were obtained on DNA from peripheral blood samples at age 49-51 (n = 351), using a quantitative polymerase chain reaction assay. RESULTS: No associations were found between telomere length measured at age 49-51 and any measures of current health status. The only significant association observed was between telomere length and gender, with females having longer telomere length than men. CONCLUSIONS: Our results suggest that telomere length measurements are unlikely to provide information of much predictive significance for an individual's health status. PMID- 27562615 TI - Anomalous Self-Experiences and positive symptoms are independently associated with emotion processing deficits in schizophrenia. AB - Social-cognitive models posit a role of Anomalous Self-Experiences (ASEs), disturbances in the subjective experience of the self, in the development and maintenance of psychosis. Theorists have suggested that ASEs may underlie the social-cognitive deficits that are common in people with schizophrenia. Positive symptoms, negative symptoms, and ASEs may interfere with the ability to perceive, use, understand, and manage emotions. In the current study, 45 people with schizophrenia and 28 healthy controls completed the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE), the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), and were rated on the Positive and Negative Syndrome Scale (PANSS). Participants with schizophrenia had higher IPASE scores and lower MSCEIT scores than the comparison group. In a series of simultaneous regressions, ASEs, but not positive or negative symptoms, were associated with Total MSCEIT scores and the Using Emotions branch score. In contrast, positive symptoms, but not ASEs or negative symptoms were associated with Perceiving and Managing Emotions branches. Both ASEs and positive symptoms independently contributed to Emotional Experiencing scores. The severity of negative symptoms was not associated with deficits in any MSCEIT scores. These results suggest unique roles for ASEs and positive symptoms in emotion processing deficits in people with schizophrenia. PMID- 27562614 TI - Developmental profiling of ASD-related shank3 transcripts and their differential regulation by valproic acid in zebrafish. AB - SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood. Here, we investigated temporal, spatial, and isoform-specific expression patterns of shank3 during zebrafish development on the basis of previous researches and the differential effects of each shank3 transcript expression after exposure to valproic acid (VPA), an ASD-associated drug. At first, we observed that both shank3a and shank3b were barely expressed at very early ages (before 24 h post-fertilization (hpf)), whereas their expression levels were increased and mainly enriched in the nervous system after 24 hpf. Secondly, all of the six shank3 transcripts gradually increased during the first 7 hpf and then decreased. Subsequently, they exhibited a second increasing peak between 1 month post-fertilization (mpf) and adulthood. Thirdly, VPA treatment affected the isoform-specific expression of zebrafish shank3. In particular, the mRNA expression levels of those isoforms that contain a SAM domain were significantly increased, whereas the mRNA expression level of those which contained an ANK domain but without a SAM domain was decreased. To conclude, our findings support the molecular diversity of shank3 in zebrafish and provide a molecular framework to understand the isoform-specific function of shank3 in zebrafish. PMID- 27562616 TI - Bayesian regression analyses of radiation modality effects on pericardial and pleural effusion and survival in esophageal cancer. AB - BACKGROUND AND PURPOSE: To evaluate radiation modality effects on pericardial effusion (PCE), pleural effusion (PE) and survival in esophageal cancer (EC) patients. MATERIALS AND METHODS: We analyzed data from 470 EC patients treated with definitive concurrent chemoradiotherapy (CRT). Bayesian semi-competing risks (SCR) regression models were fit to assess effects of radiation modality and prognostic covariates on the risks of PCE and PE, and death either with or without these preceding events. Bayesian piecewise exponential regression models were fit for overall survival, the time to PCE or death, and the time to PE or death. All models included propensity score as a covariate to correct for potential selection bias. RESULTS: Median times to onset of PCE and PE after RT were 7.1 and 6.1months for IMRT, and 6.5 and 5.4months for 3DCRT, respectively. Compared to 3DCRT, the IMRT group had significantly lower risks of PE, PCE, and death. The respective probabilities of a patient being alive without either PCE or PE at 3-years and 5-years were 0.29 and 0.21 for IMRT compared to 0.13 and 0.08 for 3DCRT. In the SCR regression analyses, IMRT was associated with significantly lower risks of PCE (HR=0.26) and PE (HR=0.49), and greater overall survival (probability of beneficial effect (pbe)>0.99), after controlling for known clinical prognostic factors. CONCLUSIONS: IMRT reduces the incidence and postpones the onset of PCE and PE, and increases survival probability, compared to 3DCRT. PMID- 27562618 TI - Memory limitations and chunking are variable and cannot explain language structure. AB - Both the Now-or-Never bottleneck and the chunking mechanisms hypothesized to cope with it are more variable than Christiansen & Chater (C&C) suggest. These constructs are, therefore, too weak to support C&C's claims for the nature of language. Key aspects of the hierarchical nature of language instead arise from the nature of sequencing of subgoals during utterance planning in language production. PMID- 27562617 TI - Spinal growth velocity versus height velocity in predicting curve progression in peri-pubertal girls with idiopathic scoliosis. AB - BACKGROUND: Height velocity (HV) is traditionally used to monitor the residual growth potential in idiopathic scoliosis (IS). The temporal timing of rapid increase in standing height often does not match exactly that of the increase in spine height. The purposes of this study were to analyze the correlation between change of angle velocity (AV) vs the changes of spinal growth velocity (SGV) and HV, and the associated predictive value on curve progression in IS. METHODS: Pre pubertal IS girls with single curve receiving standardized bracing treatment followed longitudinally with documented curve progression >5 degrees were retrospectively reviewed. The age, standing height, Cobb angle (main curve), spinal length, Risser sign, HV, SGV and AV at each visit were measured and calculated. The visit with the highest AV value of each patient was selected for the final analysis and correlated with the corresponding peak height velocity (PHV) and peak spinal growth velocity (PSGV). RESULTS: Sixty-two IS girls were reviewed. Chi-square test revealed PSGV contributed more to the highest AV than PHV (P = 0.001). Pearson correlation analysis demonstrated that AV was correlated with SGV (r = 0.454, P < 0.001) and HV (r = 0.280, P = 0.027). Multiple linear regression analysis showed that high AV was better predicted by higher SGV (B = 0.321, P = 0.007) rather than higher HV (B = 0.259, P = 0.362) (R = 0.467). CONCLUSIONS: Variations of spinal growth velocity exerted more direct influence over changes in angle velocity as compared with height velocity. High spinal growth velocity predisposed to more rapid curve progression in patients with idiopathic scoliosis. PMID- 27562619 TI - Human carbonyl reductase 1 as efficient catalyst for the reduction of glutathionylated aldehydes derived from lipid peroxidation. AB - Human recombinant carbonyl reductase 1 (E.C. 1.1.1.184, hCBR1) is shown to efficiently act as aldehyde reductase on glutathionylated alkanals, namely 3 glutathionyl-4-hydroxynonanal (GSHNE), 3-glutathionyl-nonanal, 3-glutathionyl hexanal and 3-glutathionyl-propanal. The presence of the glutathionyl moiety appears as a necessary requirement for the susceptibility of these compounds to the NADPH-dependent reduction by hCBR1. In fact the corresponding alkanals and alkenals, and the cysteinyl and gamma-glutamyl-cysteinyl alkanals adducts were either ineffective or very poorly active as CBR1 substrates. Mass spectrometry analysis reveals the ability of hCBR1 to reduce GSHNE to the corresponding GS dihydroxynonane (GSDHN) and at the same time to catalyze the oxidation of the hemiacetal form of GSHNE, generating the 3-glutathionylnonanoic-delta-lactone. These data are indicative of the ability of the enzyme to catalyze a disproportion reaction of the substrate through the redox recycle of the pyridine cofactor. A rationale for the observed preferential activity of hCBR1 on different GSHNE diastereoisomers is given by molecular modelling. These results evidence the potential of hCBR1 acting on GSHNE to accomplish a dual role, both in terms of HNE detoxification and, through the production of GSDHN, in terms of involvement into the signalling cascade of the cellular inflammatory response. PMID- 27562620 TI - Feasibility and Midterm Results of Endovascular Treatment of Hepatic Artery Occlusion within 24 Hours after Living-Donor Liver Transplantation. AB - PURPOSE: To evaluate the feasibility and midterm results of endovascular treatment of hepatic artery occlusion within 24 hours after living-donor liver transplantation (LDLT). MATERIALS AND METHODS: From January 2012 to June 2014, 189 consecutive patients at a single institution underwent LDLT with right-lobe grafts. Among them, 10 were diagnosed with hepatic artery occlusion within 24 hours after LDLT. All 10 underwent endovascular treatment, including drug-eluting stent placement (n = 2), intraarterial thrombolysis (n = 5), or both (n = 3). Every patient received regular follow-up with multidetector computed tomography (CT). Data on primary technical success, primary and assisted primary patency, and biliary complications were analyzed. RESULTS: Primary technical success was achieved in all 10 cases. Primary patency rates at 1 week, 3 months, and 6 months were all 70% (7 of 10), and the respective assisted primary patency rates were all 80% (8 of 10). Bleeding at the anastomotic site developed in 2 failed cases, prompting repeat liver transplantation. All 8 successfully recanalized cases showed hepatic artery patency on CT throughout follow-up (mean, 643.6 d; range, 236-1,081 d). Six of these cases had anastomotic biliary stricture, 4 of which were successfully treated by multisession biliary intervention. One patient had nonanastomotic biliary stricture and died of hepatic failure despite lifelong external drainage. CONCLUSIONS: Endovascular treatment could be an alternative therapeutic option for patients with hepatic artery occlusion within 24 hours after LDLT. It could help achieve long-term patency of the hepatic artery, but biliary stricture can potentially occur, and bleeding at the anastomotic site is a serious complication. PMID- 27562621 TI - Validation of Clinical Scoring Systems ART and ABCR after Transarterial Chemoembolization of Hepatocellular Carcinoma. AB - PURPOSE: To perform an external validation of the Assessment for Retreatment with Transarterial Chemoembolization (ART) and alpha-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC), Child-Pugh, and response (ABCR) scores and to compare them in terms of prognostic power. MATERIALS AND METHODS: From 2000 to 2015, 871 patients with hepatocellular carcinoma underwent transarterial chemoembolization at a tertiary referral hospital, and 176 met all inclusion and exclusion criteria for both scores and were analyzed. Nineteen percent (n = 34) had BCLC stage A disease and 81% had stage B disease. Thirty-nine patients (22%) presented with elevated AFP levels. Overall survival was calculated. Scores were validated and compared with a Harrell C-index, integrated Brier score (IBS), and prediction error curves. RESULTS: Before the second chemoembolization procedure, 22 patients (12%) showed an increase of 1 point in Child-Pugh score and 51 patients (22%) had an increase of >= 2 points. Thirty-one patients (23%) showed a > 25% increase in aspartate aminotransferase level, and 114 (65%) showed a response to treatment. Consequently, 127 patients (72%) had a low ART score and 49 (28%) had a high ART score. One hundred fifty-eight patients (90%) had a low ABCR score, whereas 18 (10%) had a high ABCR score. Low and high ART score groups had median survival durations of 20.8 and 15.3 mo, respectively. Harrell C-indexes were 0.572 and 0.608, and IBSs were 0.135 and 0.128, for ART and ABCR, respectively. For both scores, an increase in Child-Pugh score >= 2 points and a radiologic response were significantly associated with survival. CONCLUSIONS: Both scores were of limited predictive value, and neither was sufficient to support clear-cut clinical decisions. Further effort is necessary to determine criteria for making valid clinical predictions. PMID- 27562623 TI - Nomenclature for factors of the HLA system, update January 2016. PMID- 27562622 TI - ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation. AB - Hepatocyte growth factor (HGF) is a potent signaling factor that acts on epithelial cells, causing them to dissociate and scatter. This migration is coordinated by a number of small GTPases, such as ARF6 and Rac1. Active ARF6 is required for HGF-stimulated migration and intracellular levels of ARF6-GTP and Rac1-GTP increase following HGF treatment. During migration, cross talk between ARF6 and Rac1 occurs through formation of a multi-protein complex containing the ARF-GEF cytohesin-2, the scaffolding protein GRASP/Tamalin, and the Rac1-GEF Dock180. Previously, the role of ARF6 in this process was unclear. We have now found that ARF6 and ARF1 regulate trafficking of GRASP and Dock180 to the plasma membrane following HGF treatment. Trafficking of GRASP and Dock180 is impaired by blocking ARF6-mediated recycling pathways and is required for HGF-stimulated Rac1 activation. Finally, HGF treatment stimulates association of GRASP and Dock180. Inhibition of ARF6 trafficking pathways traps GRASP and Dock180 as a complex in the cell. PMID- 27562624 TI - Nomenclature for factors of the HLA system, update February 2016. PMID- 27562625 TI - Nomenclature for factors of the HLA system, update March 2016. PMID- 27562626 TI - Corrigendum. PMID- 27562627 TI - Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system. AB - Mechanical stimuli and neovascularization are closely coupled to osteogenic differentiation and new bone formation. The purpose of present study was to detect the effect of cyclic mechanical strain on a co-culture system of bone marrow stromal cells (BMSCs) and vascular endothelial cells (VECs) and to clarify the related mechanisms. Primary BMSCs and VECs were isolated from Sprague-Dawley rats and co-cultured at various ratios (1:0, 1:2, 1:4, 4:1, 2:1, 1:1, and 0:1). To determine optimized loading conditions, the cells were then subjected to various cyclic tensile strains (0%, 3%, 6% and 9%) using a Flexcell 5000 mechanical loading system. A protocol of 6% strain on the co-cultured cells at a 1:1 ratio was selected as the optimized culture conditions based on the best osteogenic effects, which included increased ALP activity, matrix mineralization and the expressions of VEGF, Runx-2 and Col-1. The VEGF-R inhibitor tivozanib was used to analyze the paracrine role of VEGF, and the osteogenesis-promoting effects of 6% tensile strain were abrogated in the co-cultured cells treated with tivozanib. These results demonstrate that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC mediated paracrine effect of VEGF on BMSCs. PMID- 27562628 TI - Effects of Chronic Stress on Cognition in Male SAMP8 Mice. AB - BACKGROUND/AIMS: Chronic stress can lead to cognitive impairment. Senescence accelerated mouse prone 8 (SAMP8) is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. METHODS: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1) mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS) groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM) test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95) and synaptophysin (SYN), which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis of SYN and PSD95. RESULTS: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. CONCLUSION: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic plasticity. PMID- 27562629 TI - Self-interested agents create, maintain, and modify group-functional culture. AB - We agree that institutions and rules are crucial for explaining human sociality, but we question the claim of there not being "alternatives to CGS [that] can easily account for the institutionalized cooperation that characterizes human societies" (target article, sect. 7). Hypothesizing that self-interested individuals coercively and collaboratively create rules, we propose that agent based hypotheses offer viable alternatives to cultural group selection (CGS). PMID- 27562630 TI - Immunomodulation and Mobilization of Progenitor Cells by Extracellular Matrix Bioscaffolds for Volumetric Muscle Loss Treatment. AB - Acellular bioscaffolds composed of extracellular matrix (ECM) have been effectively used to promote functional tissue remodeling in both preclinical and clinical studies of volumetric muscle loss, but the mechanisms that contribute to such outcomes are not fully understood. Thirty-two C57bl/6 mice were divided into eight groups of four animals each. A critical-sized defect was created in the quadriceps muscle and was repaired with a small intestinal submucosa ECM bioscaffold or left untreated. Animals were sacrificed at 3, 7, 14, or 56 days after surgery. The spatiotemporal cellular response in both treated and untreated groups was characterized by immunolabeling methods. Early time points showed a robust M2-like macrophage phenotype following ECM treatment in contrast to the predominant M1-like macrophage phenotype present in the untreated group. ECM implantation promoted perivascular stem cell mobilization, increased presence of neurogenic progenitor cells, and was associated with myotube formation. These cell types were present not only at the periphery of the defect near uninjured muscle, but also in the center of the ECM-filled defect. ECM bioscaffolds modify the default response to skeletal muscle injury, and provide a microenvironment conducive to a constructive healing response. PMID- 27562631 TI - Qualitative study on the implementation of professional pharmacy services in Australian community pharmacies using framework analysis. AB - BACKGROUND: Multiple studies have explored the implementation process and influences, however it appears there is no study investigating these influences across the stages of implementation. Community pharmacy is attempting to implement professional services (pharmaceutical care and other health services). The use of implementation theory may assist the achievement of widespread provision, support and integration. The objective was to investigate professional service implementation in community pharmacy to contextualise and advance the concepts of a generic implementation framework previously published. METHODS: Purposeful sampling was used to investigate implementation across a range of levels of implementation in community pharmacies in Australia. Twenty-five semi structured interviews were conducted and analysed using a framework methodology. Data was charted using implementation stages as overarching themes and each stage was thematically analysed, to investigate the implementation process, the influences and their relationships. Secondary analyses were performed of the factors (barriers and facilitators) using an adapted version of the Consolidated Framework for Implementation Research (CFIR), and implementation strategies and interventions, using the Expert Recommendations for Implementing Change (ERIC) discrete implementation strategy compilation. RESULTS: Six stages emerged, labelled as development or discovery, exploration, preparation, testing, operation and sustainability. Within the stages, a range of implementation activities/steps and five overarching influences (pharmacys' direction and impetus, internal communication, staffing, community fit and support) were identified. The stages and activities were not applied strictly in a linear fashion. There was a trend towards the greater the number of activities considered, the greater the apparent integration into the pharmacy organization. Implementation factors varied over the implementation stages, and additional factors were added to the CFIR list and definitions modified/contextualised for pharmacy. Implementation strategies employed by pharmacies varied widely. Evaluations were lacking. CONCLUSIONS: The process of implementation and five overarching influences of professional services implementation in community pharmacy have been outlined. Framework analysis revealed, outside of the five overarching influences, factors influencing implementation varied across the implementation stages. It is proposed at each stage, for each domain, the factors, strategies and evaluations should be considered. The Framework for the Implementation of Services in Pharmacy incorporates the contextualisation of implementation science for pharmacy. PMID- 27562632 TI - Protein Adsorption and Reorganization on Nanoparticles Probed by the Coffee-Ring Effect: Application to Single Point Mutation Detection. AB - The coffee-ring effect denotes the accumulation of particles at the edge of an evaporating sessile drop pinned on a substrate. Because it can be detected by simple visual inspection, this ubiquitous phenomenon can be envisioned as a robust and cost-effective diagnostic tool. Toward this direction, here we systematically analyze the deposit morphology of drying drops containing polystyrene particles of different surface properties with various proteins (bovine serum albumin (BSA) and different forms of hemoglobin). We show that deposit patterns reveal information on both the adsorption of proteins onto particles and their reorganization following adsorption. By combining pattern analysis with adsorption isotherm and zeta potential measurements, we show that the suppression of the coffee-ring effect and the formation of a disk-shaped pattern is primarily associated with particle neutralization by protein adsorption. However, our findings also suggest that protein reorganization following adsorption can dramatically invert this tendency. Exposure of hydrophobic (respectively charged) residues can lead to disk (respectively ring) deposit morphologies independently of the global particle charge. Surface tension measurements and microscopic observations of the evaporating drops show that the determinant factor of the deposit morphology is the accumulation of particles at the liquid/gas interface during evaporation. This general behavior opens the possibility to probe protein adsorption and reorganization on particles by the analysis of the deposit patterns, the formation of a disk being the robust signature of particles rendered hydrophobic by protein adsorption. We show that this method is sensitive enough to detect a single point mutation in a protein, as demonstrated here by the distinct patterns formed by human native hemoglobin h HbA and its mutant form h-HbS, which is responsible for sickle cell anemia. PMID- 27562634 TI - Directional Reflective Surface Formed via Gradient-Impeding Acoustic Meta Surfaces. AB - Artificially designed acoustic meta-surfaces have the ability to manipulate sound energy to an extraordinary extent. Here, we report on a new type of directional reflective surface consisting of an array of sub-wavelength Helmholtz resonators with varying internal coiled path lengths, which induce a reflection phase gradient along a planar acoustic meta-surface. The acoustically reshaped reflective surface created by the gradient-impeding meta-surface yields a distinct focal line similar to a parabolic cylinder antenna, and is used for directive sound beamforming. Focused beam steering can be also obtained by repositioning the source (or receiver) off axis, i.e., displaced from the focal line. Besides flat reflective surfaces, complex surfaces such as convex or conformal shapes may be used for sound beamforming, thus facilitating easy application in sound reinforcement systems. Therefore, directional reflective surfaces have promising applications in fields such as acoustic imaging, sonic weaponry, and underwater communication. PMID- 27562633 TI - Proteomic comparison reveals the contribution of chloroplast to salt tolerance of a wheat introgression line. AB - We previously bred a salt tolerant wheat cv. SR3 with bread wheat cv. JN177 as the parent via asymmetric somatic hybridization, and found that the tolerance is partially attributed to the superior photosynthesis capacity. Here, we compared the proteomes of two cultivars to unravel the basis of superior photosynthesis capacity. In the maps of two dimensional difference gel electrophoresis (2D DIGE), there were 26 differentially expressed proteins (DEPs), including 18 cultivar-based and 8 stress-responsive ones. 21 of 26 DEPs were identified and classified into four categories, including photosynthesis, photosynthesis system stability, linolenic acid metabolism, and protein synthesis in chloroplast. The chloroplast localization of some DEPs confirmed that the identified DEPs function in the chloroplast. The overexpression of a DEP enhanced salt tolerance in Arabidopsis thaliana. In line with these data, it is concluded that the contribution of chloroplast to high salinity tolerance of wheat cv. SR3 appears to include higher photosynthesis efficiency by promoting system protection and ROS clearance, stronger production of phytohormone JA by enhancing metabolism activity, and modulating the in chloroplast synthesis of proteins. PMID- 27562635 TI - Enhanced synergistic anti-Lewis lung carcinoma effect of a DNA vaccine harboring a MUC1-VEGFR2 fusion gene used with GM-CSF as an adjuvant. AB - In order to achieve a synergistic effect on anti-tumour and anti-angiogenesis activity, we designed and constructed a DNA vaccine that expresses MUC1and VEGFR2 in the same reading frame. The aim of this study was to investigate the anti tumour activity of this DNA vaccine. Furthermore, we also investigated the enhanced synergistic anti-Lewis lung carcinoma effect of this DNA vaccine by using GM-CSF as an adjuvant. A series of DNA plasmids encoding MUC1, VEGFR2, GM CSF, and their conjugates were constructed and injected into mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were detected by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT), respectively. To evaluate the anti-tumour efficacy of these plasmids, murine models with MUC1-expressing tumours were generated. After injection into the tumour-bearing mouse model, the plasmid carrying the fusion gene of MUC1 and VEGFR2 showed stronger inhibition of tumour growth than the plasmid expressing MUC1 or VEGFR2 alone, which indicated that MUC1 and VEGFR2 could exert a synergistic anti-tumour effect. Furthermore, mice vaccinated with the combination of the GM-CSF expressing plasmid and the plasmid carrying the fusion gene of MUC1 and VEGFR2 showed an increased inhibition in the growth of MUC1-expressing tumours and prolonged mouse survival. These observations emphasize the potential of the synergistic anti-tumour and anti angiogenesis strategy used in DNA vaccines, and the potential of the GM-CSF gene as an adjuvant for DNA vaccines, which could represent a promising approach for tumour immunotherapy. PMID- 27562636 TI - Differences in autonomy of humans and ultrasocial insects. AB - The target article is built on an analogy between humans and ultrasocial insects. We argue that there are many important limitations to the analogy that make any possible inferences from the analogy questionable. We demonstrate the issue using an example of the difference between a loss of autonomy in humans and in social insects. PMID- 27562637 TI - Computational specificity in the human brain. AB - Although meta-analytic neuroimaging studies demonstrate a relative lack of specificity in the brain, this evidence may be the result of limits inherent to these types of studies. From this perspective, we review recent findings that suggest that brain function is most appropriately categorized according to the computational capacity of each brain system, rather than the specific task states that elicit its activity. PMID- 27562638 TI - Abnormal white matter tracts resembling pencil fibers involving prefrontal cortex (Brodmann area 47) in autism: a case report. AB - BACKGROUND: Autism is not correlated with any neuropathological hallmark as the brain of autistic individuals lack defined lesions. However, previous investigations have reported cortical heterotopias and local distortion of the cytoarchitecture of the neocortex in some cases of autism. CASE PRESENTATION: Our patient was a 40-year-old white woman diagnosed at an early age with autism and mental retardation. Pencil fibers were present within the prefrontal cortex (Brodmann area 47) and its composition resembled that of the underlying white matter region. Pencil fibers encompassed most of the extent of the cortical grey matter and were populated by oligodendrocytes, astrocytes, and microglial cells, but not by neurons. CONCLUSIONS: Here we report a new cytoarchitectural abnormality that has not been previously described in autism. Future pathological examinations should keep in mind the potential presence of pencil fibers within the prefrontal cortex of cases with autism. PMID- 27562639 TI - Heart blood flow simulation: a perspective review. AB - Cardiovascular disease (CVD), the leading cause of death today, incorporates a wide range of cardiovascular system malfunctions that affect heart functionality. It is believed that the hemodynamic loads exerted on the cardiovascular system, the left ventricle (LV) in particular, are the leading cause of CVD initiation and propagation. Moreover, it is believed that the diagnosis and prognosis of CVD at an early stage could reduce its high mortality and morbidity rate. Therefore, a set of robust clinical cardiovascular assessment tools has been introduced to compute the cardiovascular hemodynamics in order to provide useful insights to physicians to recognize indicators leading to CVD and also to aid the diagnosis of CVD. Recently, a combination of computational fluid dynamics (CFD) and different medical imaging tools, image-based CFD (IB-CFD), has been widely employed for cardiovascular functional assessment by providing reliable hemodynamic parameters. Even though the capability of CFD to provide reliable flow dynamics in general fluid mechanics problems has been widely demonstrated for many years, up to now, the clinical implications of the IB-CFD patient specific LVs have not been applicable due to its limitations and complications. In this paper, we review investigations conducted to numerically simulate patient specific human LV over the past 15 years using IB-CFD methods. Firstly, we divide different studies according to the different LV types (physiological and different pathological conditions) that have been chosen to reconstruct the geometry, and then discuss their contributions, methodologies, limitations, and findings. In this regard, we have studied CFD simulations of intraventricular flows and related cardiology insights, for (i) Physiological patient-specific LV models, (ii) Pathological heart patient-specific models, including myocardial infarction, dilated cardiomyopathy, hypertrophic cardiomyopathy and hypoplastic left heart syndrome. Finally, we discuss the current stage of the IB-CFD LV simulations in order to mimic realistic hemodynamics of patient-specific LVs. We can conclude that heart flow simulation is on the right track for developing into a useful clinical tool for heart function assessment, by (i) incorporating most of heart structures' (such as heart valves) operations, and (ii) providing useful diagnostic indices based hemodynamic parameters, for routine adoption in clinical usage. PMID- 27562640 TI - A Multirelational Social Network Analysis of an Online Health Community for Smoking Cessation. AB - BACKGROUND: Online health communities (OHCs) provide a convenient and commonly used way for people to connect around shared health experiences, exchange information, and receive social support. Users often interact with peers via multiple communication methods, forming a multirelational social network. Use of OHCs is common among smokers, but to date, there have been no studies on users' online interactions via different means of online communications and how such interactions are related to smoking cessation. Such information can be retrieved in multirelational social networks and could be useful in the design and management of OHCs. OBJECTIVE: To examine the social network structure of an OHC for smoking cessation using a multirelational approach, and to explore links between subnetwork position (ie, centrality) and smoking abstinence. METHODS: We used NetworkX to construct 4 subnetworks based on users' interactions via blogs, group discussions, message boards, and private messages. We illustrated topological properties of each subnetwork, including its degree distribution, density, and connectedness, and compared similarities among these subnetworks by correlating node centrality and measuring edge overlap. We also investigated coevolution dynamics of this multirelational network by analyzing tie formation sequences across subnetworks. In a subset of users who participated in a randomized, smoking cessation treatment trial, we conducted user profiling based on users' centralities in the 4 subnetworks and identified user groups using clustering techniques. We further examined 30-day smoking abstinence at 3 months postenrollment in relation to users' centralities in the 4 subnetworks. RESULTS: The 4 subnetworks have different topological characteristics, with message board having the most nodes (36,536) and group discussion having the highest network density (4.35*10(-3)). Blog and message board subnetworks had the most similar structures with an in-degree correlation of .45, out-degree correlation of .55, and Jaccard coefficient of .23 for edge overlap. A new tie in the group discussion subnetwork had the lowest probability of triggering subsequent ties among the same two users in other subnetworks: 6.33% (54,142/855,893) for 2-tie sequences and 2.13% (18,207/855,893) for 3-tie sequences. Users' centralities varied across the 4 subnetworks. Among a subset of users enrolled in a randomized trial, those with higher centralities across subnetworks generally had higher abstinence rates, although high centrality in the group discussion subnetwork was not associated with higher abstinence rates. CONCLUSIONS: A multirelational approach revealed insights that could not be obtained by analyzing the aggregated network alone, such as the ineffectiveness of group discussions in triggering social ties of other types, the advantage of blogs, message boards, and private messages in leading to subsequent social ties of other types, and the weak connection between one's centrality in the group discussion subnetwork and smoking abstinence. These insights have implications for the design and management of online social networks for smoking cessation. PMID- 27562641 TI - Rationale and motivating factors for treatment-free remission in chronic myeloid leukemia. AB - With BCR-ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, many patients with chronic myeloid leukemia in chronic phase (CML-CP) can expect to live near-normal life spans. Current treatment recommendations of the National Comprehensive Cancer Network and the European LeukemiaNet state that patients with CML-CP should remain on TKI therapy indefinitely. However, there is increasing evidence from clinical trials that some patients with sustained deep molecular responses may be able to achieve treatment-free remission (TFR), whereby they can suspend TKI therapy without losing previously achieved responses. With many patients achieving deep molecular responses to TKI therapy, there is growing interest in whether such patients can achieve TFR. In addition, adverse events (AEs) with long-term TKI therapy, including both the potential for later-emerging AEs and chronic, low-grade AEs, represent a major motivator for oncologists and their patients to investigate the feasibility of TFR. In this review, we provide an overview of data from TFR clinical trials, discuss the importance of achieving a deep molecular response to TKI treatment, and consider potential reasons for investigating TFR following TKI therapy. PMID- 27562642 TI - Surface Monocrystallization of Copper Foil for Fast Growth of Large Single Crystal Graphene under Free Molecular Flow. AB - Wafer-sized single-crystalline Cu (100) surface can be readily achieved on stacked polycrystalline Cu foils via simple oxygen chemisorption-induced reconstruction, enabling fast growth of large-scale millimeter-sized single crystalline graphene arrays under molecular flow. The maximum growth rate can reach 300 MUm min-1 , several orders of magnitude higher than previously reported values for millimeter-sized single-crystalline graphene growth on Cu foils. PMID- 27562643 TI - Dietary change mediates relationships between stress during pregnancy and infant head circumference measures: the QF2011 study. AB - Prenatal maternal stress can adversely affect birth outcomes, likely reflecting effects of maternal stress hormones on fetal development. Maternal stress might also induce behavioural changes, such as dietary change, that might influence fetal development. Few studies have documented relationships between stress and dietary change in pregnancy. We analysed stress and dietary change among 222 pregnant women exposed to the 2011 Queensland Floods. We assessed women's objective hardship, subjective distress and cognitive appraisal of the disaster; changes in their diets and their associations with infants' gestational age, weight, length and head circumference at birth, head circumference to birth length ratio (HC/BL) and ponderal index. Greater objective hardship was correlated with more negative dietary change, skipped meals and skipped multivitamins. There were no direct effects of stress or dietary change on birth outcomes. However, we observed an interactive effect of dietary change and exposure timing on head circumference for gestational age (HC for GA) (p = 0.010) and a similar trend for HC/BL (p = 0.064). HC for GA and HC/BL were larger among children whose mothers experienced negative changes to their diet in early pregnancy compared with later pregnancy, consistent with a 'head-sparing' response with early gestation exposure. Further analyses indicated that dietary change mediates the relationship between objective hardship because of the floods and these outcomes. This is the first report of relationships among an independent stressor, dietary change and birth outcomes. It highlights another possible mechanism in the relationship between prenatal maternal stress and child development that could guide future research and interventions. PMID- 27562644 TI - Frida Kahlo: Portrait of Chronic Pain. AB - The Mexican artist Frida Kahlo (1907-1954) is one of the most celebrated artists of the 20th century. Although famous for her colorful self-portraits and associations with celebrities Diego Rivera and Leon Trotsky, less known is the fact that she had lifelong chronic pain. Frida Kahlo developed poliomyelitis at age 6 years, was in a horrific trolley car accident in her teens, and would eventually endure numerous failed spinal surgeries and, ultimately, limb amputation. She endured several physical, emotional, and psychological traumas in her lifetime, yet through her art, she was able to transcend a life of pain and disability. Of her work, her self-portraits are conspicuous in their capacity to convey her life experience, much of which was imbued with chronic pain. Signs and symptoms of chronic neuropathic pain and central sensitization of nociceptive pathways are evident when analyzing her paintings and medical history. This article uses a narrative approach to describe how events in the life of this artist contributed to her chronic pain. The purpose of this article is to discuss Frida Kahlo's medical history and her art from a modern pain sciences perspective, and perhaps to increase our understanding of the pain experience from the patient's perspective. PMID- 27562645 TI - The drosomycin multigene family: three-disulfide variants from Drosophila takahashii possess antibacterial activity. AB - Drosomycin (DRS) is a strictly antifungal peptide in Drosophila melanogaster, which contains four disulfide bridges (DBs) with three buried in molecular interior and one exposed on molecular surface to tie the amino- and carboxyl termini of the molecule together (called wrapper disulfide bridge, WDB). Based on computational analysis of genomes of Drosophila species belonging to the Oriental lineage, we identified a new multigene family of DRS in Drosphila takahashii that includes a total of 11 DRS-encoding genes (termed DtDRS-1 to DtDRS-11) and a pseudogene. Phylogenetic tree and synteny analyses reveal orthologous relationship between DtDRSs and DRSs, indicating that orthologous genes of DRS-1, DRS-2, DRS-3 and DRS-6 have undergone duplication in D. takahashii and three amplifications (DtDRS-9 to DtDRS-11) of DRS-3 have lost WDB. Among the 11 genes, five are transcriptionally active in adult fruitflies. The ortholog of DRS (DtDRS 1) shows high structural and functional similarity to DRS while two WDB-deficient members display antibacterial activity accompanying complete loss or remarkable reduction of antifungal activity. To the best of our knowledge, this is the first report on the presence of three-disulfide antibacterial DRSs in a specific Drosophila species, suggesting a potential role of DB loss in neofunctionalization of a protein via structural adjustment. PMID- 27562647 TI - Automated Ki-67 Quantification of Immunohistochemical Staining Image of Human Nasopharyngeal Carcinoma Xenografts. AB - Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches. PMID- 27562646 TI - TNIK inhibition abrogates colorectal cancer stemness. AB - Canonical Wnt/beta-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and beta-catenin transcriptional complex. Consistent with this, Tnik deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik(-/-)/Apc(min/+) mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB 0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apc(min/+) mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID- 27562648 TI - Liposomal angiogenic peptides for ischemic limb perfusion: comparative study between different administration methods. AB - BACKGROUND: We investigated the therapeutic effectiveness of PEGylated liposomes loaded with angiogenic peptides for treating hindlimb ischemia. METHODS: Rats received a femoral artery occlusion. Red blood cells collected from the animals were labeled with technetium-99m. Limb perfusion gamma imaging was performed. PEGylated liposomes loaded with angiogenic peptides were administered intra arterially. Technetium-99m red blood cell imaging was repeated 1 week later. The animals were sacrificed the next day. The expression of angiogenic proteins was studied. Later, changes in limb perfusion after intra-arterial infusion versus intra-muscular injection were also compared to determine the therapeutic effectiveness of different administration methods. RESULTS: Femoral artery occlusion dramatically reduced ischemic limb perfusion (by an average of 69%, compared to contralateral limb). This was not different among groups (p > 0.05). Liposomes loaded with angiogenic peptides significantly improved ischemic limb perfusion, compared to controls (210% of baseline, versus 100% of baseline in control; p < 0.05 versus controls). The enhanced ischemic limb perfusion was accompanied by an increased expression of CD 31 (an average of 1.6-fold increase of controls; p < 0.05). The liposomes or peptides treatment alone did not affect ischemic perfusion (liposomes alone: 100% of baseline; peptides alone: 120% of baseline; p > 0.05 versus controls, respectively) or the angiogenic response (1.1 fold of controls in liposomes alone; 1.0-fold of controls in peptides alone; p > 0.05 versus controls, respectively). Intra-muscular injection induced similar liposomal treatment effects on ischemic limb perfusion (230% of baseline) as those by intra-arterial infusion (210% of baseline; p < 0.05 versus intra muscular). CONCLUSIONS: PEGylated liposomes loaded with angiogenic peptides improved ischemic limb perfusion and promoted angiogenic responses. Liposomal angiogenic treatment via intra-arterial infusion resulted in an equally effective therapeutic efficacy compared to that of intra-muscular injection. These results show the therapeutic potential of our liposomal strategy for treating peripheral limb ischemia. PMID- 27562649 TI - The influence of floral traits on specialization and modularity of plant pollinator networks in a biodiversity hotspot in the Peruvian Andes. AB - BACKGROUND AND AIMS: Modularity is a ubiquitous and important structural property of ecological networks which describes the relative strengths of sets of interacting species and gives insights into the dynamics of ecological communities. However, this has rarely been studied in species-rich, tropical plant-pollinator networks. Working in a biodiversity hotspot in the Peruvian Andes we assessed the structure of quantitative plant-pollinator networks in nine valleys, quantifying modularity among networks, defining the topological roles of species and the influence of floral traits on specialization. METHODS: A total of 90 transects were surveyed for plants and pollinators at different altitudes and across different life zones. Quantitative modularity (QuanBiMo) was used to detect modularity and six indices were used to quantify specialization. KEY RESULTS: All networks were highly structured, moderately specialized and significantly modular regardless of size. The strongest hubs were Baccharis plants, Apis mellifera, Bombus funebris and Diptera spp., which were the most ubiquitous and abundant species with the longest phenologies. Species strength showed a strong association with the modular structure of plant-pollinator networks. Hubs and connectors were the most centralized participants in the networks and were ranked highest (high generalization) when quantifying specialization with most indices. However, complementary specialization d' quantified hubs and connectors as moderately specialized. Specialization and topological roles of species were remarkably constant across some sites, but highly variable in others. Networks were dominated by ecologically and functionally generalist plant species with open access flowers which are closely related taxonomically with similar morphology and rewards. Plants associated with hummingbirds had the highest level of complementary specialization and exclusivity in modules (functional specialists) and the longest corollas. CONCLUSIONS: We have demonstrated that the topology of networks in this tropical montane environment was non-random and highly organized. Our findings underline that specialization indices convey different concepts of specialization and hence quantify different aspects, and that measuring specialization requires careful consideration of what defines a specialist. PMID- 27562651 TI - Assessment of personality-related levels of functioning: a pilot study of clinical assessment of the DSM-5 level of personality functioning based on a semi structured interview. AB - BACKGROUND: The personality disorder categories in the Diagnostic and Statistical Manual of Mental Disorders IV have been extensively criticized, and there is a growing consensus that personality pathology should be represented dimensionally rather than categorically. The aim of this pilot study was to test the Clinical Assessment of the Level of Personality Functioning Scale, a semi-structured clinical interview, designed to assess the Level of Personality Functioning Scale of the DSM-5 (Section III) by applying strategies similar to what characterizes assessments in clinical practice. METHODS: The inter-rater reliability of the assessment of the four domains and the total impairment in the Level of Personality Functioning Scale were measured in a patient sample that varied in terms of severity and type of pathology. Ratings were done independently by the interviewer and two experts who watched a videotaped Clinical Assessment of the Level of Personality Functioning Scale interview. RESULTS: Inter-rater reliability coefficients varied between domains and were not sufficient for clinical practice, but may support the use of the interview to assess the dimensions of personality functioning for research purposes. CONCLUSIONS: While designed to measure the Level of Personality Functioning Scale with a high degree of similarity to clinical practice, the Clinical Assessment of the Level of Personality Functioning Scale had weak reliabilities and a rating based on a single interview should not be considered a stand-alone assessment of areas of functioning for a given patient. PMID- 27562652 TI - Stroke: Are care and outcomes better for participants of stroke trials? PMID- 27562653 TI - Complete De Novo Assembly of Monoclonal Antibody Sequences. AB - De novo protein sequencing is one of the key problems in mass spectrometry-based proteomics, especially for novel proteins such as monoclonal antibodies for which genome information is often limited or not available. However, due to limitations in peptides fragmentation and coverage, as well as ambiguities in spectra interpretation, complete de novo assembly of unknown protein sequences still remains challenging. To address this problem, we propose an integrated system, ALPS, which for the first time can automatically assemble full-length monoclonal antibody sequences. Our system integrates de novo sequencing peptides, their quality scores and error-correction information from databases into a weighted de Bruijn graph to assemble protein sequences. We evaluated ALPS performance on two antibody data sets, each including a heavy chain and a light chain. The results show that ALPS was able to assemble three complete monoclonal antibody sequences of length 216-441 AA, at 100% coverage, and 96.64-100% accuracy. PMID- 27562654 TI - The childhood obesity strategy. PMID- 27562656 TI - Acupuncture for stroke rehabilitation. AB - BACKGROUND: Stroke is the second most common cause of death in the world and in China it has now become the main cause of death. It is also a main cause of adult disability and dependency. Acupuncture for stroke has been used in China for hundreds of years and is increasingly practiced in some Western countries. This is an update of the Cochrane review originally published in 2006 . OBJECTIVES: To determine the efficacy and safety of acupuncture therapy in people with subacute and chronic stroke. We intended to test the following hypotheses: 1) acupuncture can reduce the risk of death or dependency in people with subacute and chronic stroke at the end of treatment and at follow-up; 2) acupuncture can improve neurological deficit and quality of life after treatment and at the end of follow up; 3) acupuncture can reduce the number of people requiring institutional care; and 4) acupuncture is not associated with any intolerable adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library 2015, Issue 7), MEDLINE (1966 to July 2015, Ovid), EMBASE (1980 to July 2015, Ovid), CINAHL (1982 to July 2015, EBSCO), and AMED (1985 to July 2015, Ovid). We also searched the following four Chinese medical databases: China Biological Medicine Database (July 2015); Chinese Science and Technique Journals Database (July 2015); China National Infrastructure (July 2015), and Wan Fang database (July 2015). SELECTION CRITERIA: Truly randomised unconfounded clinical trials among people with ischaemic or haemorrhagic stroke, in the subacute or chronic stage, comparing acupuncture involving needling with placebo acupuncture, sham acupuncture, or no acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed quality, extracted and cross-checked the data. MAIN RESULTS: We included 31 trials with a total of 2257 participants in the subacute or chronic stages of stroke. The methodological quality of most of the included trials was not high. The quality of evidence for the main outcomes was low or very low based on the assessment by the system of Grades of Recommendation, Assessment, Development and Evaluation (GRADE).Two trials compared real acupuncture plus baseline treatment with sham acupuncture plus baseline treatment. There was no evidence of differences in the changes of motor function and quality of life between real acupuncture and sham acupuncture for people with stroke in the convalescent stage.Twenty-nine trials compared acupuncture plus baseline treatment versus baseline treatment alone. Compared with no acupuncture, for people with stroke in the convalescent phase, acupuncture had beneficial effects on the improvement of dependency (activity of daily living) measured by Barthel Index (nine trials, 616 participants; mean difference (MD) 9.19, 95% confidence interval (CI) 4.34 to 14.05; GRADE very low), global neurological deficiency (seven trials, 543 participants; odds ratio (OR) 3.89, 95% CI 1.78 to 8.49; GRADE low), and specific neurological impairments including motor function measured by Fugl-Meyer Assessment (four trials, 245 participants; MD 6.16, 95% CI 4.20 to 8.11; GRADE low), cognitive function measured by the Mini-Mental State Examination (five trials, 278 participants; MD 2.54, 95% CI 0.03 to 5.05; GRADE very low), depression measured by the Hamilton Depression Scale (six trials, 552 participants; MD -2.58, 95% CI -3.28 to -1.87; GRADE very low), swallowing function measured by drinking test (two trials, 200 participants; MD -1.11, 95% CI -2.08 to -0.14; GRADE very low), and pain measured by the Visual Analogue Scale (two trials, 118 participants; MD -2.88, 95% CI 3.68 to -2.09; GRADE low). Sickness caused by acupuncture and intolerance of pain at acupoints were reported in a few participants with stroke in the acupuncture groups. No data on death, the proportion of people requiring institutional care or requiring extensive family support, and all-cause mortality were available in all included trials. AUTHORS' CONCLUSIONS: From the available evidence, acupuncture may have beneficial effects on improving dependency, global neurological deficiency, and some specific neurological impairments for people with stroke in the convalescent stage, with no obvious serious adverse events. However, most included trials were of inadequate quality and size. There is, therefore, inadequate evidence to draw any conclusions about its routine use. Rigorously designed, randomised, multi-centre, large sample trials of acupuncture for stroke are needed to further assess its effects. PMID- 27562655 TI - Midterm outcome after surgical correction of anomalous left coronary artery from the pulmonary artery. AB - BACKGROUND: This study was undertaken to determine the midterm outcome in patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) undergoing coronary reimplantation and Takeuchi repair. METHODS: A retrospective review of patients who had ALCAPA repair between January 2009 and December 2015. Mortality, echocardiography assessment of left ventricular function including ejection fractionand, shortening fraction, severity of mitral regurgitation, stenosis of the coronary ostium were studied retrospectively. RESULTS: Sixteen patients were described. The mean age at the time of surgery was 22.5 +/- 10.3 years (range, 9 months-35.6 years) and 2 patients were younger than 1 year old, Surgical interventions included left coronary artery reimplantation in 13 patients (81 %) and Takeuchi repair in 3 (19 %). Concomitant mitral valve repair was performed in 2 cases, no cases required mechanical circulatory support postoperatively. There was no mortality. At median follow-up of 4.6 years, EF improved from 33.2 % +/-6.8 % to 60.9 % +/- 8.1 % (p <0.05), mean SF from 28.5 % +/- 12.1 % to 40.2 % +/- 5.4 % (p <0.05). Only one patient was with moderate mitral regurgitation. All 16 cases had normal ejection fraction and shortening fraction without stenosis of the coronary ostium at last follow-up. CONCLUSIONS: Early establishment of a 2-coronary artery achieved excellent outcomes without morbidity and mechanical circulatory support. Normal ejection fraction and shortening fraction recovered smoothly. There is no stenosis of the coronary ostium at the midterm follow-up. PMID- 27562657 TI - Nitratireductor lacus sp. nov., isolated from Yuncheng Salt Lake, China. AB - This is the taxonomic study of a novel bacterial strain, designated GSS14T, isolated from a sediment sample of Yuncheng Salt Lake, China. Cells were Gram negative, ovoid to rod-shaped and motile by means of flagella. The isolate could grow at 10-45 degrees C, at pH 6.5-11.0 and in the presence of 0-12 % (w/v) NaCl. The dominant fatty acids were summed feature 8 (consisting of C18 : 1omega7c and/or C18 : 1omega6c; 76.7 %) and the DNA G+C content was 61 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain GSS14T was affiliated with the genus Nitratireductor, and it was most closely related to Nitratireductor kimnyeongensis KY 101T (98.2 % 16S rRNA gene sequence similarity) and Nitratireductor aquibiodomus JCM 21793T (96.6 %). DNA-DNA hybridization between strains GSS14T and N. kimnyeongensis KY 101T revealed 52 % relatedness. Phenotypic, chemotaxonomic and phylogenetic data support assignment of this isolate to the genus Nitratireductor as a representative of a novel species. The name Nitratireductor lacus sp. nov. is proposed, with strain GSS14T (=KCTC 52186T=MCCC 1K02481) as the type strain. PMID- 27562658 TI - Sharp Contradiction for Local-Hidden-State Model in Quantum Steering. AB - In quantum theory, no-go theorems are important as they rule out the existence of a particular physical model under consideration. For instance, the Greenberger Horne-Zeilinger (GHZ) theorem serves as a no-go theorem for the nonexistence of local hidden variable models by presenting a full contradiction for the multipartite GHZ states. However, the elegant GHZ argument for Bell's nonlocality does not go through for bipartite Einstein-Podolsky-Rosen (EPR) state. Recent study on quantum nonlocality has shown that the more precise description of EPR's original scenario is "steering", i.e., the nonexistence of local hidden state models. Here, we present a simple GHZ-like contradiction for any bipartite pure entangled state, thus proving a no-go theorem for the nonexistence of local hidden state models in the EPR paradox. This also indicates that the very simple steering paradox presented here is indeed the closest form to the original spirit of the EPR paradox. PMID- 27562659 TI - Difficulties Choosing Control Points in Acupuncture Research. Response: Commentary: Differential Cerebral Response, Measured with Both an EEG and fMRI, to Somatosensory Stimulation of a Single Acupuncture Point vs. Two Non Acupuncture Points. PMID- 27562661 TI - Knowledge translation: What it is and the relevance to evidence-based healthcare and nursing. PMID- 27562660 TI - Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness. AB - BACKGROUND: Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in airway hyperresponsiveness (AHR) and inflammation. However, the role of nociceptin at modulating the inflammatory immune microenvironment in asthma is still unclear. OBJECTIVE: To understand the role of N/OFQ in the regulation of a Th2-like environment, we used a conventional murine model of AHR. METHODS: Balb/c and CD1 mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. A group of Balb/c mice were killed at 7 and 14 days from the first sensitization for the inflammatory profile evaluation while a group of Balb/c and CD1 mice were aerosol-challenged from day 21 to 23 with OVA and killed 24 h later for functional evaluations. RESULTS: In OVA-sensitized mice, N/OFQ significantly reduced IL-4+ CD4+ T cells in lymph nodes (LN) and IL 13 in the lungs, while it induced IFN-gamma increase in the lung. The efflux of dendritic cells (DCs) to the mediastinic LN and into the lung of OVA-sensitized mice was reduced in N/OFQ-treated and sensitized mice. N/OFQ reduced the expression of CD80 on DCs, indicating its ability to modulate the activation of DCs. In a less prone Th2-like environment mice strain, such as CD1 mice, N/OFQ did not modify lung resistances as observed in BALB/c mice. Finally, spectroscopic data showed the N/OFQ was able to interact onto the membrane of DCs obtained from Balb/c rather than CD1 mice, indicating its ability to modulate AHR in a Th2-like environment with a direct activity on DCs. CONCLUSIONS AND CLINICAL RELEVANCE: Our data confirmed the capability of N/OFQ to modulate the immune microenvironment in the lung of Th2-biased, OVA-sensitized Balb/c mice, suggesting N/OFQ-NOP axis as a novel pharmacological tool to modulate the inflammatory immune microenvironment in asthma. PMID- 27562663 TI - The effect of hospital nurse staffing models on patient and staff-related outcomes. PMID- 27562662 TI - Evidence implementation: Development of an online methodology from the knowledge to-action model of knowledge translation. AB - This paper describes an online facilitation for operationalizing the knowledge-to action (KTA) model. The KTA model incorporates implementation planning that is optimally suited to the information needs of clinicians. The can-implement((c)) is an evidence implementation process informed by the KTA model. An online counterpart, the can-implement.pro((c)) , was developed to enable greater dissemination and utilization of the can-implement((c)) process. The driver for this work was health professionals' need for facilitation that is iterative, informed by context and localized to the specific needs of users. The literature supporting this paper includes evaluation studies and theoretical concepts relevant to KTA model, evidence implementation and facilitation. Nursing and other health disciplines require a skill set and resources to successfully navigate the complexity of organizational requirements, inter-professional leadership and day-to-day practical management to implement evidence into clinical practice. The can-implement.pro((c)) provides an accessible, inclusive system for evidence implementation projects. There is empirical support for evidence implementation informed by the KTA model, which in this phase of work has been developed for online uptake. Nurses and other clinicians seeking to implement evidence could benefit from the directed actions, planning advice and information embedded in the phases and steps of can-implement.pro((c)) . PMID- 27562664 TI - Implementation of evidence-based health care using action research: An emancipatory approach. AB - The aim of the study is to discuss the emancipatory approach to action research as an appropriate methodology for workers' meaningful implementation of evidence based health care. Implementation of evidence-based health care using action research is well supported by the literature. There are various approaches to action research, and they are coherent with the objectives and methods elected to develop the investigation. It is not clear which approach of action research is responsible for meaningful worker engagement in changing praxis. This is a discussion paper based on our experiences and supported by literature on collective health. Health care is defined as a social praxis, dependent upon the capitalist mode of production in which health workers engage themselves in a labour process that has negative (as alienation) as well as positive (as creativity) meanings. Emancipatory changes of social praxis through implementation of evidence-based health care require that participants understand the positive and negative meanings of their work and engage health workers in a conscious and intentional collaborative educational process. Implementation of evidence-based health care through emancipatory action research is capable of overcoming alienation and changing social practice through a participatory meaningful process of knowledge translation. PMID- 27562665 TI - Implementation of evidence-based practice by nurses working in community settings and their strategies to mentor student nurses to develop evidence-based practice: A qualitative study. AB - The aim of the study was to explore how community nurses apply the best available evidence to their practice, and how they mentor student nurses to conceptualize and implement evidence-based practice in community settings. In the UK, the expansion of health-care provision in the community has supported the development of highly skilled community nurses. However, there is limited literature regarding the strategies used by community nurses to implement evidence-based practice and mentor student nurses to conceptualize evidence-based practice in community placements. An exploratory qualitative approach applying inductive reasoning to focus group data was used. As a result, nurses working for a community NHS Foundation Trust in South England with a mentor qualification were invited to participate in one of the seven focus groups, 33 nurses participated. Data were analyzed with thematic analysis. The themes discussed in this paper are: 'our practice is evidence-based' as guidelines and policies provided structure, but occasionally stifled autonomous clinical decision-making, and 'time' as a barrier and facilitator to mentoring student nurses in community settings. In conclusion, nurses need to develop the ability to incorporate patients' needs and wishes within evidence-based care. Time was a facilitator for some community mentors, but protected time is required to complete the necessary practice documentation of student nurses. PMID- 27562667 TI - Proposal of an integrative model of adjustment to chronic conditions: An understanding of the process of psychosocial adjustment to living with type 2 diabetes. AB - Psychosocial adjustment to living with a chronic condition was explored in this grounded theory study, focusing on type 2 diabetes. Despite a range of relevant theories, there is limited understanding of the process of adjustment. The study aimed to address this issue. That was achieved through collecting and analysing personal narratives using individual interviews and focus groups. This allowed for the development of a normative integrative model of adjustment to chronic conditions based on biopsychosocial principles. The integrative model of adjustment to chronic condition has the potential to lead to improved understanding of adjustment processes. PMID- 27562666 TI - Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline. AB - RATIONALE: Several model organisms have been employed to study the impacts of stress on biological systems. Different models of unpredictable chronic stress (UCS) have been established in rodents; however, these protocols are expensive, long-lasting, and require a large physical structure. Our group has recently reported an UCS protocol in zebrafish with several advantages compared to rodent models. We observed that UCS induced behavioral, biochemical, and molecular changes similar to those observed in depressed patients, supporting the translational relevance of the protocol. OBJECTIVES: Considering that a pharmacological assessment is lacking in this zebrafish model, our aim was to evaluate the effects of anxiolytic (bromazepam) and antidepressant drugs (fluoxetine and nortriptyline) on behavioral (novel tank test), biochemical (whole-body cortisol), and molecular parameters (cox-2, tnf-alpha, il-6, and il 10 gene expression) in zebrafish subjected to UCS. RESULTS: We replicated previous data showing that UCS induces behavioral and neuroendocrine alterations in zebrafish, and we show for the first time that anxiolytic and antidepressant drugs are able to prevent such effects. Furthermore, we extended the molecular characterization of the model, revealing that UCS increases expression of the pro inflammatory markers cox-2 and il-6, which was also prevented by the drugs tested. CONCLUSIONS: This study reinforces the use of zebrafish as a model organism to study the behavioral and physiological effects of stress. The UCS protocol may also serve as a screening tool for evaluating new drugs that can be used to treat psychiatric disorders with stress-related etiologies. PMID- 27562668 TI - Expanding the use of Twitter for medical education. PMID- 27562669 TI - Comments on Van den Wyngaert et al., The EANM practice guidelines for bone scintigraphy. PMID- 27562670 TI - Assessing Quality of Care for the Myelodysplastic Syndromes. AB - Measuring the quality of care for patients with chronic cancers is difficult, especially for heterogeneous malignancies such as the myelodysplastic syndromes (MDS). Recent work suggests that improvements may be needed in the quality of diagnostic, treatment, and end-of-life care for patients with these syndromes. Moreover, rigorous assessment of factors that are necessary to deliver high quality care such as preferred method of decision-making and pre-treatment quality of life are often overlooked. Finally, a key component of quality care is that it is received equitably across different patient populations, yet several recent studies suggest that there are financial, educational, race-ethnic, and age-related barriers to equitable MDS care. PMID- 27562672 TI - Risk of cancer in Asian Americans: a Kaiser Permanente cohort study. AB - PURPOSE: To supplement published cohort data about incident cancer in Asian Americans (Asians) including risk of specific Asian ethnic groups. METHODS: A cohort study in 124,193 persons (13,344 Asians) with baseline examination data in 1978-1985 used Cox proportional hazards models with seven covariates to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: Through 2012 cancer was diagnosed in 18,687 persons including 1,522 Asians. Compared to Whites, the HR (CIs) for any cancer in Asians was 0.8 (0.7-0.9, p < 0.001). Lower Asian risk was stronger for men (HR = 0.7, p < 0.001) than for women (HR = 0.9, p = 0.003). Lower Asian vs. White risks with p < 0.05 were found for cancers of the upper airway digestive area, hematologic malignancies, melanoma, and cancers of the prostate, bladder, and brain. Melanoma contributed substantially to lower Asian risk, especially in women. HRs for specific Asian groups versus Whites follow: Chinese = 0.9 (p < 0.001), Japanese = 0.9 (p = 0.01), Filipinos = 0.8 (p < 0.001), South Asians = 0.5 (p < 0.001), and Other Asians = 0.7 (p = 0.006). Both South Asian men and women had lower risk than Whites, and South Asians had lower risk than any other racial/ethnic group. CONCLUSIONS: Asians had lower cancer risk than Whites, due to lower risk of several cancer types. Each Asian ethnic group had lower risk than Whites with South Asians at the lowest risk. PMID- 27562671 TI - A Cell-type-resolved Liver Proteome. AB - Parenchymatous organs consist of multiple cell types, primarily defined as parenchymal cells (PCs) and nonparenchymal cells (NPCs). The cellular characteristics of these organs are not well understood. Proteomic studies facilitate the resolution of the molecular details of different cell types in organs. These studies have significantly extended our knowledge about organogenesis and organ cellular composition. Here, we present an atlas of the cell-type-resolved liver proteome. In-depth proteomics identified 6000 to 8000 gene products (GPs) for each cell type and a total of 10,075 GPs for four cell types. This data set revealed features of the cellular composition of the liver: (1) hepatocytes (PCs) express the least GPs, have a unique but highly homogenous proteome pattern, and execute fundamental liver functions; (2) the division of labor among PCs and NPCs follows a model in which PCs make the main components of pathways, but NPCs trigger the pathways; and (3) crosstalk among NPCs and PCs maintains the PC phenotype. This study presents the liver proteome at cell resolution, serving as a research model for dissecting the cell type constitution and organ features at the molecular level. PMID- 27562673 TI - Height is an indicator of vascular maintenance capacity in older men. AB - AIM: Bone-derived circulating CD34-positive cells are reported to play an important role in vascular maintenance. Additionally, height might influence age related hematopoietic bone marrow decline, as it positively correlates with total bone marrow volume. As hypertension should mask the beneficial effects of circulating CD34-positive cells, hypertension status should account for this correlation. The present study aimed to clarify the clinical importance of height on vascular maintenance in older Japanese men. METHODS: We carried out a cross sectional study of 343 older men aged 65-69 years who underwent a general health checkup from 2013 to 2015. RESULTS: Independent of known cardiovascular risk factors, height was found to be slightly, but significantly, positively correlated with the log number of circulating CD34-positive cells in systolic, but not non-systolic, hypertensive men. Multilinear regression analysis showed a parameter estimate (B) and standardized parameter estimate (beta) of 3.23 * 10-2 , 0.28 (P = 0.003) for systolic hypertensive men and -0.49 * 10-2 , -0.04 (P = 0.495) for non-systolic hypertensive men. CONCLUSIONS: Height positively correlates with circulating CD34-positive cells in systolic, but not non systolic, hypertensive men. As the beneficial effects of circulating CD34 positive cells on endothelial repair might be masked by hypertension where the production of CD34-positive cells is stimulated by hypertension-induced vascular damage, among individuals with systolic hypertension, circulating CD34-positive cells should indicate the limits of endothelial repair. Therefore, height might indicate the capacity for adequate vascular maintenance in older men. Geriatr Gerontol Int 2017; 17: 1729-1736. PMID- 27562674 TI - Sensory determinants of stated liking for vegetable names and actual liking for canned vegetables: A cross-country study among European adolescents. AB - Sensory properties are reported as one of the main factors hindering an appropriate vegetable intake by the young. In the present work the sensory determinants of likings for vegetables were explored in adolescents of four European countries (Denmark, n = 88; France, n = 206; Italy, n = 110 and United Kingdom, n = 93). A questionnaire was designed to study cross country differences in stated liking for and familiarity with a list of vegetables popular among European markets (between-vegetable approach). A within-vegetable comparison approach with actual tasting was used to analyze differences and similarities in liking for canned pea and sweet corn samples across the countries. A close positive relationship between stated liking and familiarity was found. Irrespective of the country, one group of highly liked vegetables (carrots, tomatoes, green salad) was identified, characterized by innately liked tastes (sweet, umami), delicate flavour and bright appealing colour. A second group of highly disliked vegetables consists of cauliflowers and broccoli, characterized by disliked sensations such as bitter taste and objectionable flavour. Internal Preference Maps from actual liking scores indicate that the generally disliked tastes (bitter, sour), are clearly correlated with a negative hedonic response for both peas and sweet corn. The hedonic valence of a generally well accepted taste such as salty and texture descriptors depends on the type of vegetable. Internal preference maps from actual liking data indicate that flavour and appearance descriptors of the distinct sensory properties of each type of vegetable positively affect liking, while the intensity of unusual flavours is related to sample disliking. PMID- 27562675 TI - Introduction to the special issue. PMID- 27562676 TI - Multisensory integration of redundant trisensory stimulation. AB - Integration of sensory information across modalities can confer behavioral advantages by decreasing perceptual ambiguity, increasing reaction time, and increasing detection accuracy relative to unisensory stimuli. We asked how combinations of auditory, visual, and somatosensory events alter response time. Participants detected stimulation on one side of space (right or left) while ignoring stimulation on the other side of space. There were seven types of suprathreshold stimuli: auditory (tones from speakers), visual (sinusoidal contrast gratings), somatosensory (fingertip vibrations), audio-visual, somato visual, audio-somatosensory, and audio-somato-visual. Response enhancement and race model analysis confirmed that bisensory and trisensory trials enhanced response time relative to unisensory trials. Exploratory analysis of individual differences in intersensory facilitation revealed that participants fit into one of two groups: those who benefitted from trisensory information and those who did not. PMID- 27562677 TI - Water-deficit stress-responsive microRNAs and their targets in four durum wheat genotypes. AB - MicroRNAs (miRNAs) guide regulation at the post-transcriptional level by inducing messenger RNA (mRNA) degradation or translational inhibition of their target protein-coding genes. Durum wheat miRNAs may contribute to the genotypic water deficit stress response in different durum varieties. Further investigation of the interactive miRNA-target regulatory modules and experimental validation of their response to water stress will contribute to our understanding of the small RNA-mediated molecular networks underlying stress adaptation in durum wheat. In this study, a comprehensive genome-wide in silico analysis using the updated Triticum transcriptome assembly identified 2055 putative targets for 113 conserved durum miRNAs and 131 targets for four novel durum miRNAs that putatively contribute to genotypic stress tolerance. Predicted mRNA targets encode various transcription factors, binding proteins and functional enzymes, which play vital roles in multiple biological pathways such as hormone signalling and metabolic processes. Quantitative PCR profiling further characterised 43 targets and 5 miRNAs with stress-responsive and/or genotype-dependent differential expression in two stress-tolerant and two stress-sensitive durum genotypes subjected to pre-anthesis water-deficit stress. Furthermore, a 5' RLM RACE approach validated nine mRNA targets cleaved by water-deficit stress responsive miRNAs, which, to our knowledge, has not been previously reported in durum wheat. The present study provided experimental evidence of durum miRNAs and target genes in response to water-deficit stress in contrasting durum varieties, providing new insights into the regulatory roles of the miRNA-guided RNAi mechanism underlying stress adaptation in durum wheat. PMID- 27562680 TI - Rome was not built in one day: Underlying biological and cognitive factors responsible for the emergence of agriculture and ultrasociality. AB - Agriculture represented a major transition in human evolution, but the appearance of ultrasociality must have included previous steps. We argue that ultrasociality would not have suddenly emerged with agriculture, but rather developed from pre existing cognitive and social mechanisms. Discussions must include necessary depth about the historical origins of human ultrasociality, and agriculture's aftereffects on large-scale social organization. PMID- 27562678 TI - Characterization of VvPAL-like promoter from grapevine using transgenic tobacco plants. AB - A 2000-bp 5'-flanking region of VvPAL-like was isolated from 'Summer Black' grapevine by PCR amplification, named pVvPAL-like. To gain a better understanding of the expression and regulatory mechanism of VvPAL-like, a chimeric expression unit consisting of the beta-glucuronidase (GUS) reporter gene under the control of a 2000-bp fragment of the VvPAL-like promoter was transformed into tobacco via Agrobacterium tumefaciens. Histochemical staining showed that the full-length promoter directs efficient expression of the reporter gene in cotyledons and hypocotyls, stigma, style, anthers, pollen, ovary, trichomes, and vascular bundles of transgenic plants. A series of 5' progressive deletions of the promoter revealed the presence of a negative regulatory region (-424 to -292) in the VvPAL-like promoter. Exposure of the transgenic tobacco plants to various abiotic stresses demonstrated that the full-length construct could be induced by light, copper (Cu), abscisic acid (ABA), indole-3-acetic (IAA), methyl jasmonate (MeJA) (N-1-naphthylphthalamic acid), ethylene, and drought. Furthermore, the ethylene-responsive region was found to be located in the -1461/-930 fragment, while the element(s) for the MeJA-responsive expression may be present in the 424/-292 region in the VvPAL-like promoter. These findings will help us to better understand the molecular mechanisms by which VvPAL-like participates in biosynthesis of flavonoids and stress responses. PMID- 27562681 TI - The mechanism underlying combined medial and lateral plantar and tibial intraneural ganglia in the tarsal tunnel. AB - Intraneural ganglion cysts in the tarsal tunnel are rare. We present a patient who had an intraneural ganglion cyst involving the medial and lateral plantar and distal tibial nerves. Magnetic resonance imaging revealed evidence to support the joint-related (i.e., subtalar) origin of the cyst. Careful reinterpretation of the imaging supported a phasic mechanism (i.e., cross-over) to explain the interrelated pathogenesis of the intraneural cyst within the three nerves. This mechanism is analogous to that described for the prototypes-the peroneal, tibial and sciatic nerves in the knee region-and can be generalized to other nerves in the foot and ankle region. We believe that understanding the pathogenesis sheds light on the effective treatment. PMID- 27562679 TI - Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcRgamma from LIR-1+ NK cells. AB - While it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR 1, NKp30, NKp46, and FcRgamma, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-alpha and CD107a expression. The most active NK cells were FcRgamma- LIR-1+ NKG2C- and displayed high antibody dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRgamma but express LIR-1. PMID- 27562682 TI - Electrophysiological interpretations of the clinical response to stimulation parameters of pallidal deep brain stimulation for cervical dystonia. AB - OBJECTIVE: Deep brain stimulation (DBS) at the posterolateral ventral portion of the globus pallidus internus (GPi) has been regarded as a good therapeutic modality. Because the theoretical principle behind the stimulation parameters is yet to be determined, this study aimed to interpret analyses of the stimulation parameters used in our department based on an electrophysiological review. METHODS: Nineteen patients with medically refractory idiopathic cervical dystonia who underwent GPi DBS were enrolled. The baseline and follow-up parameters were analyzed according to their dependence on time after DBS. The pattern of changes in the stimulation parameters over time, the differences across the four active contacts, and the relationship between the stimulation parameters and clinical benefits were evaluated. RESULTS: Mean age and disease duration were 50.9 years and 54.7 months, respectively. Mean follow-up duration was 22.6 months. The amplitude and frequency exhibited significant increasing temporal patterns, i.e., a mean amplitude and frequency of 3.1 V and 132.2 Hz at the initial setting and 4.0 V and 142.6 Hz at the last follow-up, respectively. The better clinical response group (clinical improvement rate of 65-100 %) used a narrower pulse width (mean value of 78.4 MUs) than the worse clinical response group (clinical improvement rate of 5-60 %, mean of value of 88.6 MUs). Active contact at the GPe was used more often in the worse clinical response group than in the better response group. CONCLUSIONS: Based on electrophysiological considerations, these patterns of stimulation parameters could be interpreted. This interpretation was based on a theoretical understanding of the mechanisms of action of DBS, i.e., that the abnormal neural signal is substituted by an induced neural signal, which is generated by therapeutic DBS. PMID- 27562683 TI - Unilateral endonasal transcribriform approach with septal transposition for olfactory groove meningioma: can olfaction be preserved? AB - BACKGROUND: Loss of olfaction has been considered inevitable in endoscopic endonasal resection of olfactory groove meningiomas. Olfaction preservation may be feasible through an endonasal unilateral transcribriform approach, with the option for expansion using septal transposition and contralateral preservation of the olfactory apparatus. METHODS: An expanded unilateral endonasal transcribriform approach with septal transposition was performed in five cadaver heads. The approach was applied in a surgical case of a 24 * 26-mm olfactory groove meningioma originating from the right cribriform plate with partially intact olfaction. RESULTS: The surgical approach offered adequate exposure to the anterior skull base bilaterally. The nasal/septal mucosa was preserved on the contralateral side. Gross total resection of the meningioma was achieved with the successful preservation of the contralateral olfactory apparatus and preoperative olfaction. Six months later, the left nasal cavity showed no disruption of the mucosal lining and the right side was at the appropriate stage of healing for a harvested nasoseptal flap. One year later, the preoperative olfactory function was intact and favorably viewed by the patient. Objective testing of olfaction showed microsomia. CONCLUSIONS: Olfaction preservation may be feasible in the endoscopic endonasal resection of a unilateral olfactory groove meningioma through a unilateral transcribriform approach with septal transposition and preservation of the contralateral olfactory apparatus. PMID- 27562684 TI - Vegetation carbon sequestration in Chinese forests from 2010 to 2050. AB - Forests store a large part of the terrestrial vegetation carbon (C) and have high C sequestration potential. Here, we developed a new forest C sequestration (FCS) model based on the secondary succession theory, to estimate vegetation C sequestration capacity in China's forest vegetation. The model used the field measurement data of 3161 forest plots and three future climate scenarios. The results showed that logistic equations provided a good fit for vegetation biomass with forest age in natural and planted forests. The FCS model has been verified with forest biomass data, and model uncertainty is discussed. The increment of vegetation C storage in China's forest vegetation from 2010 to 2050 was estimated as 13.92 Pg C, while the average vegetation C sequestration rate was 0.34 Pg C yr 1 with a 95% confidence interval of 0.28-0.42 Pg C yr-1 , which differed significantly between forest types. The largest contributor to the increment was deciduous broadleaf forest (37.8%), while the smallest was deciduous needleleaf forest (2.7%). The vegetation C sequestration rate might reach its maximum around 2020, although vegetation C storage increases continually. It is estimated that vegetation C sequestration might offset 6-8% of China's future emissions. Furthermore, there was a significant negative relationship between vegetation C sequestration rate and C emission rate in different provinces of China, suggesting that developed provinces might need to compensate for undeveloped provinces through C trade. Our findings will provide valuable guidelines to policymakers for designing afforestation strategies and forest C trade in China. PMID- 27562685 TI - Estimating and mapping the incidence of dengue and chikungunya in Honduras during 2015 using Geographic Information Systems (GIS). AB - Geographical information systems (GIS) use for development of epidemiological maps in dengue has been extensively used, however not in other emerging arboviral diseases, nor in Central America. Surveillance cases data (2015) were used to estimate annual incidence rates of dengue and chikungunya (cases/100,000 pop) to develop the first maps in the departments and municipalities of Honduras. The GIS software used was Kosmo Desktop 3.0RC1(r). Four thematic maps were developed according departments, municipalities, diseases incidence rates. A total of 19,289 cases of dengue and 85,386 of chikungunya were reported (median, 726 cases/week for dengue and 1460 for chikungunya). Highest peaks were observed at weeks 25th and 27th, respectively. There was association between progression by weeks (p<0.0001). The cumulated crude national rate was estimated in 224.9 cases/100,000 pop for dengue and 995.6 for chikungunya. The incidence rates ratio between chikungunya and dengue is 4.42 (ranging in municipalities from 0.0 up to 893.0 [San Vicente Centenario]). Burden of both arboviral diseases is concentrated in capital Central District (>37%, both). Use of GIS-based epidemiological maps allow to guide decisions-taking for prevention and control of diseases that still represents significant issues in the region and the country, but also in emerging conditions. PMID- 27562687 TI - Gestalt-like representations hijack Chunk-and-Pass processing. AB - Christiansen & Chater (C&C) make two related and somewhat contradictory claims, namely that the ever abstract language representations built during Chunk-and Pass processing allow for ever greater interference from extra-linguistic information, and that it is nevertheless the language system that re-codes incoming information into abstract representations. I analyse these claims and discuss evidence suggesting that Gestalt-like representations hijack Chunk-and Pass processing. PMID- 27562686 TI - Imaging alpha4beta2 Nicotinic Acetylcholine Receptors (nAChRs) in Baboons with [18F]XTRA, a Radioligand with Improved Specific Binding in Extra-Thalamic Regions. AB - PURPOSE: Currently available positron-emitting radiotracers for imaging of the alpha4beta2 subtype of nicotinic acetylcholine receptors (nAChRs) exhibit high and moderate specific binding in the thalamus and extra-thalamic brain regions, respectively. In many neuropsychiatric disorders, alpha4beta2-nAChRs are altered in the extra-thalamic brain regions, but not necessarily in the thalamus. The purpose of this study was to evaluate [18F]XTRA, a new alpha4beta2-nAChR positron emission tomography (PET) radioligand with improved specific binding in extra thalamic brain regions, in non-human primates. PROCEDURES: The regional distribution of [18F]XTRA in the brain of Papio anubis baboons was evaluated in baseline and blocking experiments. Various PET modeling procedures were used for determination of volume of distribution (V T), binding potential (BPND), and receptor occupancy. Radiation dosimetry for [18F]XTRA was studied in male CD-1 mice and extrapolated to human dosimetry estimates using OLINDA/EXM software. RESULTS: [18F]XTRA was synthesized using an automated radiochemistry module with 25 % decay-corrected radiochemical yield. [18F]XTRA readily enters the baboon brain and specifically labels alpha4beta2-nAChRs. Mathematical modeling demonstrates high binding potential values (BPND = 7 and 1.3 in the thalamus and frontal cortex, respectively). A PET scanning time of 90-120 min was sufficient to obtain stable V T values in the extra-thalamic regions. The extrapolated human effective dose was 0.041 mSv/MBq (0.15 Rem/mCi). CONCLUSION: [18F]XTRA exhibits improved specific binding in the baboon brain including extra-thalamic regions and it is considered radiologically acceptable for human studies. Further evaluations of [18F]XTRA in human subjects are under way. PMID- 27562689 TI - The future of surgical training in the context of the 'Shape of Training' Review: Consensus recommendations by the Association of Surgeons in Training. AB - ASiT has long maintained that in order to provide the best quality care to patients in the UK and Republic of Ireland, it is critical that surgeons are trained to the highest standards. In addition, it is imperative that surgery remains an attractive career choice, with opportunities for career progression and job satisfaction to attract and retain the best candidates. In 2013, the Shape of Training review report set out recommendations for the structure and delivery of postgraduate training in light of an ever increasingly poly-morbid and ageing population. This consensus statement outlines ASIT's position regarding recommendations for improving surgical training and aims to help guide discussions with regard to future proposed changes to surgical training. PMID- 27562688 TI - Generation of Febrile Seizures and Subsequent Epileptogenesis. AB - Febrile seizures (FSs) occur commonly in children aged from 6 months to 5 years. Complex (repetitive or prolonged) FSs, but not simple FSs, can lead to permanent brain modification. Human infants and immature rodents that have experienced complex FSs have a high risk of subsequent temporal lobe epilepsy. However, the causes of FSs and the mechanisms underlying the subsequent epileptogenesis remain unknown. Here, we mainly focus on two major questions concerning FSs: how fever triggers seizures, and how epileptogenesis occurs after FSs. The risk factors responsible for the occurrence of FSs and the epileptogenesis after prolonged FSs are thoroughly summarized and discussed. An understanding of these factors can provide potential therapeutic targets for the prevention of FSs and also yield biomarkers for identifying patients at risk of epileptogenesis following FSs. PMID- 27562690 TI - Anaesthetics and analgesics; neurocognitive effects, organ protection and cancer reoccurrence an update. AB - Available general and local anaesthetics, third generation inhaled anaesthetics, propofol and amide class local anaesthetics are effective and reassuringly safe. They are all associated to low incidence of toxicology and or adverse-effects. There is however a debate whether anaesthetic drug and technique could exhibit effects beyond the primary effects; fully reversible depression of the central nervous system, dose dependent anaesthesia. Anaesthetics may be involved in the progression of neurocognitive side effects seen especially in the elderly after major surgery, so called Postoperative Cognitive Dysfunction. On the other hand anaesthetics may exhibit organ protective potential, reducing ischemia reperfusion injury and improving survival after cardiac surgery. Anaesthetics and anaesthetic technique may also have effects of cancer reoccurrence and risk for metastasis. The present paper provides an update around the evidence base around anaesthesia potential contributing effect on the occurrence of postoperative cognitive adverse-effects, organ protective properties and influence on cancer re occurrence/metastasis. PMID- 27562692 TI - Regioselective Functionalization of 3-Hydroxy-pyridine Carboxylates by Neighboring Group Assistance. AB - Regioselective hydrolysis, transesterification, and aminolysis of unactivated, highly substituted pyridine esters were realized under mild conditions by employing neighboring group assisted catalysis. Excellent yields were achieved without active removal of the alcohol byproduct. Regioselective aminolysis had a considerable substrate scope ([hetero]aryl, alkyl and amino acid). A mechanism involving assistance by the deprotonated phenolic OH-group is suggested for hydrolysis and transesterification. PMID- 27562691 TI - Recommendation for axillary lymph node dissection in women with early breast cancer and sentinel node metastasis: A systematic review and meta-analysis of randomized controlled trials using the GRADE system. AB - BACKGROUND: In 2014, the American Society of Clinical Oncology published an updated clinical practice guideline on axillary lymph node dissection (ALND) for early-stage breast cancer patients. However, these recommendations have been challenged because they were based on data from only one randomized controlled trial (RCT). We evaluated the rationale of these recommendations by systematically reviewing RCTs using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. METHODS: We searched articles in the PubMed, EMBASE, CINAHL, Scopus, and Cochrane databases. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were recurrence rate and surgical complications of axillary dissection. The quality of evidence was assessed using the GRADE profiler. RESULTS: Five eligible studies were retrieved and analyzed. We divided sentinel lymph node (SLN) metastasis into two categories: SLN micrometastasis and SLN macrometastasis. In patients with 1 or 2 SLN micrometastasis, no significant difference was observed in OS, DFS, or recurrence rate between the ALND and non ALND groups. For patients with 1 or 2 SLN marcometastasis, only one trial with a moderate risk of bias was included, and non-ALND was the preferred management overall. However, ALND might be appropriate for patients who placed a greater emphasis on longer-term survival at any cost. CONCLUSION: We recommend non-ALND management for early breast cancer patients with 1 or 2 SLN micrometastasis or macrometastasis on the basis of a systematic review of the current evidence conducted using the GRADE system. However, the optimal practice of evidence-based medicine should incorporate patient preferences, particularly when evidence is limited. PMID- 27562693 TI - Minimal energetic expenditure of women walking burdened on gradients in urban environments. AB - OBJECTIVES: The objective is to understand the walking energy expenditure of women in urban environments (i.e., over-ground), using mass, velocity, gradient (incline and decline), and burden as predictors. In addition, we use an equation to determine the gradient associated with the minimum energy expenditure of walking. METHODS: To do this, we assessed the volumetric consumption of oxygen (VO2 ) of ten females (ages: 22-40 years) with a portable Cosmed K4b2 device. Participants walked at three self-selected, over-ground velocities (slow, normal, and fast) on five gradients (0%, +/-7.5%, +/- 12.4%) in different urban community settings burdened (10 kg) and unburdened. We performed a multilinear regression controlling for repeated measures to determine the best predictive equation for VO2 . The first derivative of our equation was used to find the gradient for minimal VO2 . RESULTS: Our equation explains 79% of the variation in VO2 and indicates that over-ground walking is similar to treadmill walking, except that the gradient associated with the minimal energy expenditure of walking is steeper (-11% to -20%) than that established from treadmill walking. CONCLUSIONS: Although our overall equation is an accurate predictor of VO2 for all velocities, burden, incline, and decline in this group, further research needs to be conducted to examine kinetic, kinematic, and velocity interactions in over-ground walking. PMID- 27562694 TI - Sensory Processing Sensitivity: Factors of the Highly Sensitive Person Scale and Their relationships to Personality and Subjective Health Complaints. AB - The aim of the present study was to examine the factor structure of a Norwegian version of the Highly Sensitive Person Scale (HSPS) and to investigate how sensory processing sensitivity (SPS) is related to personality traits of neuroticism, extraversion, and openness and to subjective health complaints (SHC) in a sample of 167 undergraduate psychology students. The results showed that the variance in a shortened version of the HSPS was best described by three separate factors: ease of excitation (EOE), aesthetic sensitivity (AES), and low sensory threshold (LST). Furthermore, the result showed than an overall SPS factor (EOE, LST, and AES combined) was predicted positively by neuroticism and openness and negatively by extraversion. With respect to SHC, the results showed that EOE and LST were positively associated with psychological health complaints. However, the personality trait of neuroticism contributed more than the SPS factors as predictor of SHC. In conclusion, the present study supported a shortened version of the HSPS and its relation to personality factors and SHC. PMID- 27562695 TI - The Rate of Expanded Inner Speech During Spontaneous Sentence Productions. AB - The rate of expanded inner speech and speech aloud was compared in 20 typical adults (3 males, 17 females; M age = 24 years, SD = 4). Participants generated and timed spontaneous sentences with both expanded inner speech and speech aloud following the instruction to say "the first thing that comes to mind." The rate of expanded inner speech was slightly, but significantly, faster than the rate of speech aloud. The findings supported the hypothesis that expanded inner speech was faster than speech aloud because of the time required to move the articulators in the latter. Physical measures of speaking rate are needed to validate self-timed measures. Limitations of the study and directions for research are discussed. PMID- 27562696 TI - Antifungal susceptibilities of non-Aspergillus filamentous fungi causing invasive infection in Australia: support for current antifungal guideline recommendations. AB - Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre((r)) YeastOne((r)) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of <=0.25 mg/L, followed by posaconazole and itraconazole at <=1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of <=0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre((r)) YeastOne((r)) offers a practical alternative to the reference methodology for susceptibility testing of moulds. PMID- 27562697 TI - Exploring some edges: Chunk-and-Pass processing at the very beginning, across representations, and on to action. AB - We identify three "working edges" for fruitful elaboration of the Chunk-and-Pass proposal: (a) accounting for the earliest phases of language acquisition, (b) explaining diversity in the stability and plasticity of different representational types, and PMID- 27562698 TI - Bactericidal and virucidal mechanisms in the alkaline disinfection of compost using calcium lime and ash. AB - In the present study, the bactericidal and virucidal mechanisms in the alkaline disinfection of compost with calcium lime and ash were investigated. Two indicator microorganisms, Escherichia coli and MS2 coliphage, were used as surrogates for enteric pathogens. The alkaline-treated compost with calcium oxide (CaO) or ash resulted primarily in damage to the outer membrane and enzyme activities of E. coli. The alkaline treatment of compost also led to the infectivity loss of the coliphage because of the partial capsid damage and RNA exteriorization due to a raised pH, which is proportional to the amount of alkaline agents added. These results indicate that the alkaline treatment of compost using calcium oxide and ash is effective and can contribute to the safe usage of compost from a mixing type dry toilet. PMID- 27562699 TI - Greywater as a sustainable water source: A photocatalytic treatment technology under artificial and solar illumination. AB - Greywater considers being a highly reclaimable water source particularly important for water-stressed nations. In this work, heterogeneous photocatalysis using artificial and solar illumination has been applied for the mineralization of simulated light greywater (effluents from dishwashers and kitchen sinks were excluded from the study). The effects on the process' efficiency of TiO2 P25 catalyst's concentration, initial concentration of H2O2 and Fe3+, pH of the solution, as well as the type of radiation, were evaluated in a bench-scale Pyrex reactor and a pilot-scale slurry fountain photoreactor. The treatment efficiency has been followed through the evolution of the organic matter content expresses as dissolved organic carbon (DOC). Best results were obtained with the photo Fenton-assisted TiO2 photocatalytic process with 72% DOC removal after 210 min of bench scale treatment, while under the same photocatalytic conditions in the pilot reactor the DOC removal reached almost 64%. Moreover, the decrease in toxicity, phytotoxicity and biodegradability of the simulated wastewater has been observed after solar-induced photocatalytic treatment. PMID- 27562700 TI - Optimization of operating parameters for gas-phase photocatalytic splitting of H2S by novel vermiculate packed tubular reactor. AB - Hydrogen production by gas-phase photocatalytic splitting of Hydrogen Sulphide (H2S) was investigated on four semiconductor photocatalysts including CuGa1.6Fe0.4O2, ZnFe2O3, (CdS + ZnS)/Fe2O3 and Ce/TiO2. The CdS and ZnS coated core shell particles (CdS + ZnS)/Fe2O3 shows the highest rate of hydrogen (H2) production under optimized conditions. Packed bed tubular reactor was used to study the performance of prepared photocatalysts. Selection of the best packing material is a key for maximum removal efficiency. Cheap, lightweight and easily adsorbing vermiculate materials were used as a novel packing material and were found to be effective in splitting H2S. Effect of various operating parameters like flow rate, sulphide concentration, catalyst dosage, light irradiation were tested and optimized for maximum H2 conversion of 92% from industrial waste H2S. PMID- 27562701 TI - Review of remediation practices regarding cadmium-enriched farmland soil with particular reference to China. AB - Cadmium-enrichment of farmland soil greatly threatens the sustainable use of soil resources and the safe cultivation of grain. This review paper briefly introduces the status of farmland soil as well as grain, which are both often polluted by cadmium (Cd) in China, and illustrates the major sources of Cd contaminants in farmland soil. In order to meet soil environmental quality standards and farmland environmental quality evaluation standards for edible agricultural products, Cd enriched farmland soil is frequently remediated with the following prevailing techniques: dig and fill, electro-kinetic remediation, chemical elution, stabilisation and solidification, phytoremediation, field management and combined remediation. Most remediation techniques are still at the stage of small-scale trial experiments in China and few techniques are assessed in field trials. After comparing the technical and economical applicability among different Cd-enriched farmland soil remediation techniques, a novel ecological and hydraulic remediation technique has been proposed, which integrated the advantages of chemical elution, solidification and stabilisation, phytoremediation and field management. The ecological and hydraulic remediation concept is based on existing irrigation and drainage facilities, ecological ditches (ponds) and agronomic measures, which mainly detoxify the Cd-enriched soil during the interim period of crop cultivation, and guarantee the grain safety during its growth period. This technique may shift the challenge from soil to water treatment, and thus greatly enhances the remediation efficiency and shortens the remediation duration. Moreover, the proposed ecological and hydraulic remediation method matches well with the practical choice of cultivation while remediation for Cd-enriched soil in China, which has negligible impacts on the normal crop cultivation process, and thus shows great potential for large area applications. PMID- 27562702 TI - In vitro effect of nicorandil on the carbachol-induced contraction of the lower esophageal sphincter of the rat. AB - The lower esophageal sphincter (LES) is a specialized region of the esophageal smooth muscle that allows the passage of a swallowed bolus into the stomach. Nitric oxide (NO) plays a major role in LES relaxation. Nicorandil possesses dual properties of a NO donor and an ATP-sensitive potassium channel (KATP channel) agonist, and is expected to reduce LES tone. This study investigated the mechanisms underlying the effects of nicorandil on the LES. Rat LES tissues were placed in an organ bath, and activities were recorded using an isometric force transducer. Carbachol-induced LES contraction was significantly inhibited by KATP channel agonists in a concentration-dependent manner; pinacidil >> nicorandil ~ diazoxide. Nicorandil-induced relaxation of the LES was prevented by pretreatment with glibenclamide, whereas N(G)-nitro-l-arginine methyl ester (l-NAME), 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin were ineffective at preventing nicorandil-induced LES relaxation. Furthermore, nicorandil did not affect high K(+)-induced LES contraction. Reverse-transcription polymerase chain reaction analysis and immunohistochemistry revealed expression of KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1) and ABCC9 (SUR2) subunits of the KATP channel in the rat lower esophagus. These findings indicate that nicorandil causes LES relaxation chiefly by activating the KATP channel, and that it may provide an additional pharmacological tool for the treatment of spastic esophageal motility disorders. PMID- 27562703 TI - Water-extracted Perilla frutescens increases endometrial receptivity though leukemia inhibitory factor-dependent expression of integrins. AB - The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways. Adhesion between Ishikawa cells and trophoblastic JAr cells stimulated by PF treatment was abolished by knock down of LIF expression or antagonism of LIFR. In addition, the expressions of integrin beta3 and beta5 were increased by PF treatment in Ishikawa cells. The PF-induced expression of integrin beta3 and beta5 was reduced with an LIFR antagonist. Neutralization of both integrins successfully blocked PF-stimulated adhesion of JAr cells and Ishikawa cells. These results suggest that PF enhanced the adhesion between Ishikawa cells and JAr cells by increasing the expression of integrin beta3 and beta5 via an LIF dependent pathway. Given the importance of endometrial receptivity in successful pregnancy, PF can be a novel and effective candidate for improving pregnancy rate. PMID- 27562704 TI - 5-HT1A receptor agonists, xaliproden and tandospirone, inhibit the increase in the number of cutaneous mast cells involved in the exacerbation of mechanical allodynia in oxaliplatin-treated mice. AB - Oxaliplatin causes peripheral neuropathy as a major dose-limiting side effect, and the control of this neuropathy is difficult. This study was designed to investigate whether prophylactic repetitive administration of 5-HT1A receptor agonists inhibits oxaliplatin-induced mechanical allodynia in mice. Repetitive administration of 5-HT1A receptor agonists (xaliproden and tandospirone) inhibited mechanical allodynia induced by a single intraperitoneal injection of oxaliplatin. These agonists also inhibited oxaliplatin-induced mast cell migration, which is involved in the induction of mechanical allodynia. These results suggest that the prophylactic repetitive administration of 5-HT1A receptor agonists attenuates oxaliplatin-induced mechanical allodynia by inhibiting the cutaneous mast cell migration. PMID- 27562705 TI - Cutaneous presentation of hepatosplenic T-cell lymphoma-a potential mimicker of primary cutaneous gamma-delta T-cell lymphoma. PMID- 27562706 TI - ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemistry and fluorescence in situ hybridization. AB - ALK gene rearrangements are identified in 2-5 % of all non-small cell lung cancer and are more common in lifetime non-smokers with adenocarcinoma, but the prevalence of ALK rearrangements is not as well characterized in long-term ex smokers (quit >10 years prior to diagnosis). Accurate and timely diagnosis of ALK rearranged tumors is of clinical importance given the remarkable response to targeted inhibitors. ALK gene rearrangement may be detected by fluorescence in situ hybridization (FISH), and abnormal expression of ALK protein may be detected by immunohistochemistry (IHC), the latter of which is faster and less expensive. The aim of this study is to evaluate the prevalence of ALK rearrangement in non smokers and long-term ex-smokers with lung adenocarcinoma and to assess the performance of IHC for the detection of ALK+ tumors when compared to FISH. Two hundred fifty-one cases of resected lung adenocarcinoma were retrospectively reviewed, including non-smokers (n = 79) or long-term ex-smokers (n = 172). ALK IHC and ALK FISH were performed on each case. Four cases demonstrated ALK rearrangement by FISH (4/251; 1.6 %). All cases were non-smokers (4/79; 5.1 %), and all were positive for ALK by IHC. No additional cases were considered positive by IHC, and only 26 (10.4 %) cases were considered equivocal using a conservative approach to interpretation, resulting in a sensitivity of 100 % and specificity of 89.5 %. ALK rearrangement was not observed in lung adenocarcinoma arising in long-term ex-smokers, whereas it is seen in up to 5.1 % of lifetime non-smokers. ALK IHC using the 5A4 antibody demonstrates high sensitivity, supporting its use as a screening test. PMID- 27562707 TI - Applicability of near-infrared spectroscopy in the monitoring of film coating and curing process of the prolonged release coated pellets. AB - Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit(r) RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at line NIR was capable to predict the thickness of Eudragit(r) RS/RL film coating in a wide range (up to 40MUm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms. PMID- 27562708 TI - Three dimensional structural insight of laser drilled orifices in osmotic pump tablets. AB - The orifice drilled in the membrane as a channel for drug delivery is the key functional part of the osmotic pumps for a controlled drug release system. Reported conventional microscopic evaluations of these orifices have been limited to measurement of two-dimensional cross-section diameters. This study was aimed at establishing a novel method to measure quantitatively the three-dimensional architectures of orifices based on synchrotron radiation X-ray microcomputed tomography (SR-MUCT). Quantitative analysis of architectures extracted from captopril osmotic pumps drilled by a range of operating parameters indicated that laser power correlated with the cross section area, volume, surface area and depth of the orifices, while scanning speed of laser beam showed inverse relationships with the above structure characters. The synchrotron radiation based Fourier transform infrared microspectroscopy mapping showed that there was no apparent chemical change in the surrounding area of the orifice compared with the normal membrane region. Thus SR-MUCT was successfully applied to marketed felodipine osmotic pumps for architectural evaluation of the orifices. In conclusion, the first three-dimensional structural insight of orifices in osmotic pump tablets by SR-MUCT and structural reconstruction for the architectures has provided deeper insight into improving the design of advanced osmotic pumps for controlled drug release. PMID- 27562709 TI - Resolving Thrombus in the Left Atrial Appendage by Edoxaban Treatment after Acute Ischemic Stroke: Report of 2 Cases. AB - Here we report first 2 cases of patients with nonvalvular atrial fibrillation with acute cardioembolic stroke in whom thrombi in the left atrial appendage (LAA) were resolved by edoxaban administration. Case 1 reports an 86-year-old woman who suddenly showed right hemiparesis and aphasia due to occlusion of the left middle cerebral artery. She received mechanical thrombectomy and recovered neurologically. Transesophageal echocardiography (TEE) performed on day 1 demonstrated thrombus in the LAA. The thrombus was resolved on day 13 after initiation of edoxaban (30 mg once daily) instead of warfarin, which was administered before stroke onset. Case 2 reports a 49-year-old man who was admitted because of the sudden onset of left hemiparesis and aphasia. TEE demonstrated thrombus in the LAA on day 4, and edoxaban therapy (60 mg once daily) was initiated. The thrombus resolution was observed on day 16, and no embolic stroke occurred. PMID- 27562710 TI - Cerebral Venous Sinus Thrombosis May Follow a Seasonal Pattern. AB - BACKGROUND: Several studies have demonstrated seasonal and temporal variations in the incidence of arterial stroke; however, for cerebral venous sinus thrombosis (CVST), such study seems lacking. The main aim of this study was to investigate whether there is any seasonal variation for CVST, and association between CVST occurrence and temperature. METHODS: This retrospective study was conducted from January 2004 to July 2015 in 2 referral centers for the patients with cerebrovascular disorders. One hundred and sixty-six consecutive patients with a hospital admission or discharge diagnosis of definite CVST were included. The incidence of CVST was compared between high-temperature and low-temperature months. RESULTS: The mean age of patients was 36.71 +/- 12.44 and 130 (78.31%) subjects were female. The highest frequency of CVST was seen in 3 months of July to September (1.69/month per year); and the lowest frequency of CVST was seen from December to April (.83/month per year). Additionally, there was a significant correlation between the mean average of temperature in each month and the frequency of CVST occurrence (r = .60, P = .03). Moreover, we found a cluster of patients, mostly females, in whom CVST occurred in cold months and accompanied visible cerebral infarct with higher occurrence of seizure, focal neurological deficit, and loss of consciousness. CONCLUSIONS: It seems that the incidence of CVST increases in high-temperature months of the year and dehydration and ensuing consequences may play an important role in such augmentation; however, the visible cerebral infarct is again more observed in low-temperature months. PMID- 27562712 TI - Detection of a novel HLA-B*46:01 variant, HLA-B*46:01:22, in a Taiwanese individual. AB - One nucleotide replacement at residue 606 of HLA-B*46:01:01 results in a new allele, HLA-B*46:01:22. PMID- 27562711 TI - Enterococcus faecalis readily colonizes the entire gastrointestinal tract and forms biofilms in a germ-free mouse model. AB - The mammalian gastrointestinal (GI) tract is a complex organ system with a twist a significant portion of its composition is a community of microbial symbionts. The microbiota plays an increasingly appreciated role in many clinically-relevant conditions. It is important to understand the details of biofilm development in the GI tract since bacteria in this state not only use biofilms to improve colonization, biofilm bacteria often exhibit high levels of resistance to common, clinically relevant antibacterial drugs. Here we examine the initial colonization of the germ-free murine GI tract by Enterococcus faecalis-one of the first bacterial colonizers of the naive mammalian gut. We demonstrate strong morphological similarities to our previous in vitro E. faecalis biofilm microcolony architecture using 3 complementary imaging techniques: conventional tissue Gram stain, immunofluorescent imaging (IFM) of constitutive fluorescent protein reporter expression, and low-voltage scanning electron microscopy (LV SEM). E. faecalis biofilm microcolonies were readily identifiable throughout the entire lower GI tract, from the duodenum to the colon. Notably, biofilm development appeared to occur as discrete microcolonies directly attached to the epithelial surface rather than confluent sheets of cells throughout the GI tract even in the presence of high (>109) fecal bacterial loads. An in vivo competition experiment using a pool of 11 select E. faecalis mutant strains containing sequence-defined transposon insertions showed the potential of this model to identify genetic factors involved in E. faecalis colonization of the murine GI tract. PMID- 27562714 TI - Hydrogen sulfide protects against TNF-alpha induced neuronal cell apoptosis through miR-485-5p/TRADD signaling. AB - BACKGROUND AND OBJECTIVE: Increasing studies suggest that miRNAs are served as responders and regulators for pathological change in human. miR-485-5p is such a miRNA that has been proved to be affected by spinal cord I/R injury. This study was to investigate the functional involvement and mechanism of miR-485-5p in sulfuretted hydrogen (H2S) protecting neural cell from injury. METHODS: In this study, serum tumor necrosis factor (TNF-alpha) and miR-485-5p were detected in 20 patients with spinal cord ischemia/reperfusion (I/R) injury and in 20 healthy control. H2S was administered by GYY4137 treatment. Two TNF-alpha-stimulated neural human cell lines, AGE1.HN and SY-SH-5Y, were used for in vitro I/R experiments. Quantitative RT-PCR was performed to determine miR-485-5p expression. QRT-PCR and western blot were respectively performed to evaluate expression of tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD). RESULTS: The result showed that serum TNF-alpha was significantly reduced in patients compared with healthy control. In vitro TNF alpha treatment dose dependently caused GE1.HN and SY-SH-5Y apoptosis, whereas this promotion action was reversed by CYY4137. Moreover, we found that H2S protected neuronal cell against apoptosis via TRADD dependent. By luciferase reporting gene assay, western blot and qRT-PCR, we confirmed that TRADD expression was regulated by miR-485-5p. Such miR-485-5p/TRADD axis was proved to be involved in GE1.HN and SY-SH-5Y neural cell-protective process of H2S. CONCLUSION: In summary, our data for the first time identifies miR-485-5p/TRADD axis in hydrogen sulfide protecting against TNF-alpha-induced neuronal cell apoptosis. PMID- 27562715 TI - Short-chain C6 ceramide sensitizes AT406-induced anti-pancreatic cancer cell activity. AB - Our previous study has shown that AT406, a first-in-class small molecular antagonist of IAPs (inhibitor of apoptosis proteins), inhibits pancreatic cancer cell proliferation in vitro and in vivo. The aim of this research is to increase AT406's sensitivity by adding short-chain C6 ceramide. We show that co-treatment of C6 ceramide dramatically potentiated AT406-induced caspase/apoptosis activation and cytotoxicity in established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells. Reversely, caspase inhibitors largely attenuated C6 ceramide plus AT406-induced above cancer cell death. Molecularly, C6 ceramide downregulated Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. Intriguingly, C6 ceramide-mediated AT406 sensitization was nullified with Bcl-2 shRNA knockdown or pretreatment of the Bcl-2 inhibitor ABT 737. In vivo, liposomal C6 ceramide plus AT406 co-administration dramatically inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) mice. The combined anti-tumor activity was significantly more potent than either single treatment. Expressions of IAPs (cIAP1/XIAP) and Bcl-2 were downregulated in Panc-1 xenografts with the co-administration. Together, we demonstrate that C6 ceramide sensitizes AT406-mediated anti-pancreatic cancer cell activity possibly via downregulating Bcl-2. PMID- 27562713 TI - Effects of a DXA result letter on satisfaction, quality of life, and osteoporosis knowledge: a randomized controlled trial. AB - BACKGROUND: Undiagnosed, or diagnosed and untreated osteoporosis (OP) increases the likelihood that falls result in hip fractures, decreased quality of life (QOL), and significant medical expenditures among older adults. We tested whether a tailored dual energy x-ray absorptiometry (DXA) test result letter and an accompanying educational bone-health brochure affected patient satisfaction, QOL, or OP knowledge. METHODS: The Patient Activation after DXA Result Notification (PAADRN) study was a double-blinded, pragmatic, randomized trial which enrolled patients from 2012 to 2014. We randomized 7,749 patients presenting for DXA at three health care institutions in the United States who were >= 50 years old and able to understand English. Intervention patients received a tailored letter four weeks after DXA containing their results, 10-year fracture risk, and a bone health educational brochure. Control patients received the results of their DXA per the usual practices of their providers and institutions. Satisfaction with bone health care, QOL, and OP knowledge were assessed at baseline and 12- and 52 weeks after DXA. Intention-to-treat analyses used multiple imputation for missing data and random effects regression models to adjust for clustering within providers and covariates. RESULTS: At 12-weeks 6,728 (86.8 %) and at 52-weeks 6,103 participants (78.8 %) completed their follow-up interviews. The intervention group was more satisfied with their bone health care compared to the usual care group at both their 12- and 52-week follow-ups (standardized effect size = 0.28 at 12-weeks and 0.17 at 52-weeks, p < 0.001). There were no differences between the intervention and usual care groups in QOL or OP knowledge at either time point. CONCLUSIONS: A tailored DXA result letter and bone-health educational brochure sent to patients improved patient satisfaction with bone related health care. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01507662 First received: December 8, 2011. PMID- 27562716 TI - Metabolic biomarkers for non-alcoholic fatty liver disease induced by high-fat diet: In vivo magnetic resonance spectroscopy of hyperpolarized [1-13C] pyruvate. AB - Hyperpolarized 13C magnetic resonance spectroscopy (MRS) to assess hepatic metabolism in non-alcoholic fatty liver disease (NAFLD) has not been reported. This study searched for cellular metabolism-based biomarkers for NAFLD induced by a high-fat diet (HFD) in rats. Also, correlations of the biomarkers with enzyme levels and histopathology were identified during a 6-week follow-up. Six rats were fed a control diet (CD) and seven rats were fed the HFD for 6 weeks. Hyperpolarized 13C dynamic MRS was performed on rat liver following an injection of hyperpolarized [1-13C] pyruvate. Compared with CD-fed rats, HFD-fed rats showed significant increases in the levels of serum alanine aminotransferase and low-density lipoprotein cholesterol at weeks 4 and 6 of follow-up. After the 6 week HFD, the ratios of [1-13C] alanine/pyruvate and [1-13C] lactate/pyruvate were significantly increased, as were the levels of alanine aminotransferase and lactate dehydrogenase, which are potentially associated with hepatosteatosis. The results implicate [1-13C] alanine and [1-13C] lactate as potentially useful noninvasive biomarkers of hepatosteatosis occurring in NAFLD. PMID- 27562717 TI - Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice. AB - Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity. PMID- 27562718 TI - The selective social learner as an agent of cultural group selection. AB - Developmental research characterizes even the youngest learners as critical and selective, capable of preserving or culling cultural information on the bases of informant accuracy, reasoning, or coherence. We suggest that Richerson et al. adjust their account of social learning in cultural group selection (CGS) by taking into consideration the role of the selective learner in the cultural inheritance system. PMID- 27562719 TI - Is salivary cortisol moderating the relationship between salivary testosterone and hand-grip strength in healthy men? AB - This study examined the moderating effect of cortisol (C) on the relationship between testosterone (T) and hand-grip strength (HGS) in healthy young men. Sixty five males were monitored for salivary T, C and HGS before and 15 min after a short bout (5 * 6-s trials) of sprint cycling exercise. Sprint exercise promoted (p < .05) positive changes in T (6.1 +/- 24.9%) and HGS (3.4 +/- 7.5%), but a negative C response (-14.4 +/- 33.1%). The T and C measures did not independently predict HGS, but a significant T * C interaction was found in relation to these outcomes. Further testing revealed that pre-test T and HGS were negatively associated (p < .05), but only in men with high C levels. The exercise changes in T and HGS were also negatively related in men with low C levels (p < .05), but no relationship was seen in men with high C levels. In summary, complex relationships between T and HGS emerged when considering C as a moderating variable. The pre-test combination of high C and low T levels favoured absolute HGS, whereas low pre-test C levels and a smaller T change were linked to larger HGS changes. These associations suggest that, in the current format, T is not necessarily anabolic to muscle strength in healthy young men. Such complexities could also explain some of the inconsistent T relationships with physical performance in lesser trained male populations. PMID- 27562720 TI - Three dimensional tubular structure self-assembled by vascular mesenchymal cells at stiffness interfaces of hydrogels. AB - In this study, we report a rational and robust methodology to construct three dimensional (3D) tubular-structures solely by self-assembly of vascular mesenchymal cells (VMCs). Using the cell-laden hyaluronic acid hydrogel surrounded by cell-free gel with a higher stiffness, VMCs spontaneously migrated across the interface and assembled into 3D tubes, which composes of numerous cells. Based on turing instability which describes the reaction-diffusion processes of inhibitors and activators, this result of 3D tubular structure formation agrees with theoretical predictions from simulations of the reaction diffusion of morphogens and cells under the initial conditions of patterned cell laden hydrogel. We showed that this combination of theoretical prediction and experiments is able to produce multi-cellular 3D tubes with desired dimensions and determinate orientation in hydrogel mimicking the 3D features of tubular tissue. This work provides a reliable methodology for creating tubular structures with controllable sizes inside the 3D hydrogel through multi-cellular self organization. PMID- 27562721 TI - Activator protein 1 promotes the transcriptional activation of IRAK-M. AB - Interleukin-1 receptor-associated kinase M (IRAK-M) is a well-known negative regulator for Toll-like receptor signaling, which can regulate immune homeostasis and tolerance in a number of pathological settings. However, the mechanism for IRAK-M regulation at transcriptional level remains largely unknown. In this study, a 1.4kb upstream sequence starting from the major IRAK-M transcriptional start site was cloned into luciferase reporter vector pGL3-basic to construct the full-length IRAK-M promoter. Luciferase reporter plasmids harboring the full length and the deletion mutants of IRAK-M were transfected into 293T and A549 cells, and their relative luciferase activity was measured. The results demonstrated that activator protein 1(AP-1) cis-element plays a crucial role in IRAK-M constitutive gene transcription. Silencing of c-Fos and/or c-Jun expression suppressed the IRAK-M promoter activity as well as its mRNA and protein expressions. As a specific inhibitor for AP-1 activation, SP600125 also significantly suppressed the basal transcriptional activity of IRAK-M, the binding activity of c-Fos/c-Jun with IRAK-M promoter, and IRAK-M protein expression. Taken together, the result of this study highlights the importance of AP-1 in IRAK-M transcription, which offers more information on the role of IRAK-M in infectious and non-infectious diseases. PMID- 27562722 TI - Long non-coding RNA UCA1 promotes the tumorigenesis in pancreatic cancer. AB - The contribution of long non-coding RNAs (lncRNAs) to tumorigenesis and metastasis of pancreatic cancer (PC) remains largely unknown. Urothelial cancer associated 1 (UCA1), which is an originally identified lncRNA in bladder cancer, has be proved to play a pivotal role in bladder cancer progression and embryonic development. In this study, we detected the mRNA expression of UCA1 in 128 PC patients by qRT-PCR, and found that UCA1 expression was significantly, up regulated in tumor tissues than that in matched adjacent non-tumor tissues (p<0.05). Clinicopathological analysis demonstrated that UCA1 expression in PC significantly correlated with malignant potential factors such as tumor size (p=0.021), depth of invasion (p=0.033), CA19-9 level (p=0.034) and tumor stage (p=0.013). Cox proportional hazards regression analysis also confirmed that high UCA1 expression was an independent prognostic biomarker of PC (p=0.046), which led to an obviously shorter 5-year overall survival (OS) compared to those patients with low UCA1 expressions (p=0.018). Furthermore, we effectively down regulated UCA1 mRNA expression by transfecting RNA interfere fragments into SW 1990 cells, and our results in vitro indicated that down-regulation of UCA1 could effectively inhibit the cell proliferative activities, induce apoptotic rate and cause cell cycle arrest in PC cells (p<0.05). Meanwhile, UCA1 expression negative correlated with p27 in PC tissues (r2=0.46, p<0.01), and knockdown of p27 partly abrogated the cell proliferative activities caused by UCA1 (p<0.05). Our results raised the possibility of using UCA1 as a potential prognostic biomarker and therapy target of PC, and down-regulation of UCA1 might be considered to be a novel molecular treatment strategy for patients with PC. PMID- 27562724 TI - Biaryl Phosphine Based Pd(II) Amido Complexes: The Effect of Ligand Structure on Reductive Elimination. AB - Kinetic studies conducted under both catalytic and stoichiometric conditions were employed to investigate the reductive elimination of RuPhos (2 dicyclohexylphosphino-2',6'-diisopropoxybiphenyl) based palladium amido complexes. These complexes were found to be the resting state in Pd-catalyzed cross-coupling reactions for a range of aryl halides and diarylamines. Hammett plots demonstrated that Pd(II) amido complexes derived from electron-deficient aryl halides or electron-rich diarylamines undergo faster rates of reductive elimination. A Hammett study employing SPhos (2-dicyclohexylphosphino-2',6' dimethoxybiphenyl) and analogues of SPhos demonstrated that electron donation of the "lower" aryl group is key to the stability of the amido complex with respect to reductive elimination. The rate of reductive elimination of an amido complex based on a BrettPhos-RuPhos hybrid ligand (2-(dicyclohexylphosphino)-3,6 dimethoxy-2',6'-diisopropoxybiphenyl) demonstrated that the presence of the 3 methoxy substituent on the "upper" ring of the ligand slows the rate of reductive elimination. These studies indicate that reductive elimination occurs readily for more nucleophilic amines such as N-alkyl anilines, N,N-dialkyl amines, and primary aliphatic amines using this class of ligands. PMID- 27562723 TI - MicroRNA-199a Targets the Fatty Acid Transport Protein 1 Gene and Inhibits the Adipogenic Trans-Differentiation of C2C12 Myoblasts. AB - BACKGROUND/AIMS: Muscle cells are able to trans-differentiate into adipocytes with adipogenesis induction. MicroRNAs (miRNAs), a class of small non-coding RNAs, widely participate in the regulation of growth and development of cells. However, the expression and regulatory role of miRNAs in the trans differentiation of muscle cell are largely unknown. METHODS: C2C12 myoblasts were inducted to adipogenesis trans-differentiation and microarrays were used to assay the changes of expression profile of miRNAs. MiR-199a, a miRNA showed significant change in the trans-differentiation, was selected for the subsequent function study via over- expression and knock down. RESULTS: Dozens of miRNAs showed different changes followed the adipogenesis trans-differentiation of C2C12 cells. In which, miR-199a was decreased in the adipogenic cells and miR-199a over expression inhibited the trans-differentiation and decreased lipid accumulation in the cells. Moreover, Fatty acid transport protein 1 (Fatp1), a major regulator of trans-membrane transportation and the oxidative metabolism of free fatty acids, was showed to be a target of miR-199a by computational and luciferase reporter assays. Additionally, Fatp1 knock-down by small interfering RNA had similar inhibitory effects on the trans-differentiation in C2C12 cells. CONCLUSION: Our study reveals an important role for miR-199a in the regulation of adipogenic trans-differentiation in muscle cells via suppression of Fatp1 gene. PMID- 27562725 TI - Bacopa monnieri (Brahmi) improved novel object recognition task and increased cerebral vesicular glutamate transporter type 3 in sub-chronic phencyclidine rat model of schizophrenia. AB - Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be a new treatment and prevention for cognitive deficits in schizophrenia by acting on cerebral VGLUT3 density. We aimed to study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups for cognitive enhancement effect study: Group 1, Control; Group 2, PCP administration; Group 3, PCP+Brahmi. A neuroprotective effect study was also carried out. Rats were again assigned to three groups: Group 1, Control; Group 2, PCP administration; Group 3, Brahmi+PCP. Discrimination ratio (DR) representing cognitive ability was obtained from a novel object recognition task. VGLUT3 immunodensity was measured in the prefrontal cortex, striatum and cornu ammonis fields 1-3 (CA1-3) using immunohistochemistry. We found reduced DR in the PCP group, which occurred alongside VGLUT3 reduction in all brain areas. PCP+Brahmi showed higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex and striatum. Brahmi+PCP group showed a higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex, striatum and CA1-3. We concluded that reduced cerebral VGLUT3 was involved in cognitive deficit in PCP-administrated rats. Receiving Brahmi after PCP restored cognitive deficit by increasing VGLUT3 in the prefrontal cortex and striatum. Receiving Brahmi before PCP prevented cognitive impairment by elevating VGLUT3 in prefrontal cortex, striatum and CA1-3. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia. PMID- 27562726 TI - Humans are ultrasocial and emotional. AB - Given the highly social nature of the human emotion system, it is likely that it subserved the evolution of ultrasociality. We review how the experience and functions of human emotions enable social processes that promote ultrasociality (e.g., cooperation). We also point out that emotion may represent one route to redress one of the negative consequences of ultrasociality: ecosystem domination. PMID- 27562727 TI - The implications of neural reuse for the future of both cognitive neuroscience and folk psychology. AB - If neural reuse is true, then: (1) fully escaping phrenology will eventually require an even less brain-centric and mechanistic cognitive neuroscience that focuses on relations and interactions between brain, body, and environment at many different scales and levels across both space and time, and (2) although scientific psychology must be heavily revised, the autonomy and irreducibility of folk psychology are assured. PMID- 27562728 TI - Social media use in healthcare: A systematic review of effects on patients and on their relationship with healthcare professionals. AB - BACKGROUND: Since the emergence of social media in 2004, a growing percentage of patients use this technology for health related reasons. To reflect on the alleged beneficial and potentially harmful effects of social media use by patients, the aim of this paper is to provide an overview of the extant literature on the effects of social media use for health related reasons on patients and their relationship with healthcare professionals. METHODS: We conducted a systematic literature review on empirical research regarding the effects of social media use by patients for health related reasons. The papers we included met the following selection criteria: (1) published in a peer-reviewed journal, (2) written in English, (3) full text available to the researcher, (4) contain primary empirical data, (5) the users of social media are patients, (6) the effects of patients using social media are clearly stated, (7) satisfy established quality criteria. RESULTS: Initially, a total of 1,743 articles were identified from which 22 were included in the study. From these articles six categories of patients' use of social media were identified, namely: emotional, information, esteem, network support, social comparison and emotional expression. The types of use were found to lead to seven identified types of effects on patients, namely improved self-management and control, enhanced psychological well-being, and enhanced subjective well-being, diminished subjective well-being, addiction to social media, loss of privacy, and being targeted for promotion. Social media use by patients was found to affect the healthcare professional and patient relationship, by leading to more equal communication between the patient and healthcare professional, increased switching of doctors, harmonious relationships, and suboptimal interaction between the patient and healthcare professional. CONCLUSIONS: Our review provides insights into the emerging utilization of social media in healthcare. In particular, it identifies types of use by patients as well as the effects of such use, which may differ between patients and doctors. Accordingly, our results framework and propositions can serve to guide future research, and they also have practical implications for healthcare providers and policy makers. PMID- 27562729 TI - Who Are the Young People Choosing Web-based Mental Health Support? Findings From the Implementation of Australia's National Web-based Youth Mental Health Service, eheadspace. AB - BACKGROUND: The adolescent and early adult years are periods of peak prevalence and incidence for most mental disorders. Despite the rapid expansion of Web-based mental health care, and increasing evidence of its effectiveness, there is little research investigating the characteristics of young people who access Web-based mental health care. headspace, Australia's national youth mental health foundation, is ideally placed to explore differences between young people who seek Web-based mental health care and in-person mental health care as it offers both service modes for young people, and collects corresponding data from each service type. OBJECTIVE: The objective of this study was to provide a comprehensive profile of young people seeking Web-based mental health care through eheadspace (the headspace Web-based counseling platform), and to compare this with the profile of those accessing help in-person through a headspace center. METHODS: Demographic and clinical presentation data were collected from all eheadspace clients aged 12 to 25 years (the headspace target age range) who received their first counseling session between November 1, 2014 and April 30, 2015 via online chat or email (n=3414). These Web-based clients were compared with all headspace clients aged 12 to 25 who received their first center-based counseling service between October 1, 2014 and March 31, 2015 (n=20,015). RESULTS: More eheadspace than headspace center clients were female (78.1% compared with 59.1%), and they tended to be older. A higher percentage of eheadspace clients presented with high or very high levels of psychological distress (86.6% compared with 73.2%), but they were at an earlier stage of illness on other indicators of clinical presentation compared with center clients. CONCLUSIONS: The findings of this study suggest that eheadspace is reaching a unique client group who may not otherwise seek help or who might wait longer before seeking help if in-person mental health support was their only option. Web-based support can lead young people to seek help at an earlier stage of illness and appears to be an important component in a stepped continuum of mental health care. PMID- 27562732 TI - Time for NHS England to accept responsibility for PrEP. PMID- 27562730 TI - TGFbeta-induced switch from adipogenic to osteogenic differentiation of human mesenchymal stem cells: identification of drug targets for prevention of fat cell differentiation. AB - BACKGROUND: Patients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis. METHODS: In order to be able to interfere with this process, we have investigated in-vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted. By means of gene expression microarray analysis, we have investigated genes which are potential targets for prevention of fat cell differentiation. RESULTS: Our data show that BMP2 promotes both adipogenic and osteogenic differentiation of hMSCs, while transforming growth factor beta (TGFbeta) inhibits differentiation into both lineages. However, when cells are cultured under adipogenic differentiation conditions, which contain cAMP enhancing agents such as IBMX of PGE2, TGFbeta promotes osteogenic differentiation, while at the same time inhibiting adipogenic differentiation. Gene expression and immunoblot analysis indicated that IBMX-induced suppression of HDAC5 levels plays an important role in the inhibitory effect of TGFbeta on osteogenic differentiation. By means of gene expression microarray analysis, we have investigated genes which are downregulated by TGFbeta under adipogenic differentiation conditions and may therefore be potential targets for prevention of fat cell differentiation. We thus identified nine genes for which FDA-approved drugs are available. Our results show that drugs directed against the nuclear hormone receptor PPARG, the metalloproteinase ADAMTS5, and the aldo-keto reductase AKR1B10 inhibit adipogenic differentiation in a dose-dependent manner, although in contrast to TGFbeta they do not appear to promote osteogenic differentiation. CONCLUSIONS: The approach chosen in this study has resulted in the identification of new targets for inhibition of fat cell differentiation, which may not only be relevant for prevention of osteoporosis, but also of obesity. PMID- 27562733 TI - Making waves: safety and efficacy of ART in women. PMID- 27562731 TI - One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men. AB - BACKGROUND: Sleep deprivation has been associated with obesity among adults, and accumulating data suggests that stearoyl-CoA desaturase 1 (SCD1) expression has a relevant impact on fatty acid (FA) composition of lipid pools and obesity. The aim of this study was to investigate the effect of one-night total sleep deprivation (TSD) on DNA methylation in the 5'-prime region of SCD1, and whether detected changes in DNA methylation are associated with SCD activity indices (product to precursor FA ratios; 16:1n-7/16:0 and 18:1n-9/18:0) derived from serum phospholipids (PL). METHODS: Sixteen young, normal-weight, healthy men completed two study sessions, one with one-night TSD and one with one-night normal sleep (NS). Sleep quality and length was assessed by polysomnography, and consisted of electroencephalography, electrooculography, and electromyography. Fasting whole blood samples were collected on the subsequent morning for analysis of DNA methylation and FAs in serum PL. Linear regression analyses were performed to assess the association between changes in DNA methylation and SCD activity indices. RESULTS: Three CpG sites close to the transcription start site (TSS) of SCD1 (cg00954566, cg24503796, cg14089512) were significantly differentially methylated in dependency of sleep duration (-log10 P-value > 1.3). Both SCD-16 and SCD-18 activity indices were significantly elevated (P < 0.05) following one night TSD, and significantly associated with DNA methylation changes of the three mentioned probes in the 5' region of SCD1. CONCLUSION: Our results suggest a relevant link between TSD, hepatic SCD1 expression and de-novo fatty acid synthesis via epigenetically driven regulatory mechanisms. PMID- 27562734 TI - A breather from daily antiretroviral therapy for adolescents. PMID- 27562735 TI - Time to accommodate antiretroviral-based HIV prevention. PMID- 27562736 TI - A cost-effective and focused model for HIV prevention. PMID- 27562737 TI - From Durban to Durban: end of AIDS further than hoped. PMID- 27562738 TI - Pharmacology supports on-demand PrEP. PMID- 27562739 TI - PrEP introduction for adolescent girls and young women. PMID- 27562740 TI - Correction to Lancet HIV 2016; 3: e361-87. PMID- 27562741 TI - The impact and cost of ending AIDS in Botswana. PMID- 27562742 TI - Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. AB - BACKGROUND: Women are under-represented in HIV antiretroviral therapy (ART) studies. Guidelines for selection of ART as initial therapy in patients with HIV 1 infection do not contain sex-specific treatment. We aimed to assess the safety and efficacy of the single tablet integrase inhibitor regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate compared with a boosted protease inhibitor regimen of ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate. METHODS: In this international, randomised, controlled, double-blind, phase 3 study (Women AntiretroViral Efficacy and Safety study [WAVES]), we recruited treatment-naive HIV-infected women with an estimated creatinine clearance of 70 mL/min or higher from 80 centres in 11 countries. Women were randomly assigned (1:1) to receive elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (integrase inhibitor regimen) or ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate (protease inhibitor based regimen); regimens were masked with matching placebos. Randomisation was done by a computer generated allocation sequence (block size four) and was stratified by HIV-1 RNA viral load and race. Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary efficacy and safety analyses. The main outcome was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by US Food and Drug Administration snapshot algorithm (prespecified non-inferiority margin of 12%). This study is registered with ClinicalTrials.gov, number NCT01705574. FINDINGS: Between Nov 28, 2012, and March 12, 2014, 575 women were enrolled. 289 were randomly assigned to receive the integrase inhibitor regimen and 286 to receive the protease inhibitor based regimen. 252 (87%) women in the integrase inhibitor group had plasma HIV-1 RNA less than 50 copies per mL at week 48 compared with 231 (81%) women in the protease inhibitor group (adjusted difference 6.5%; 95% CI 0.4-12.6). No participant had virological failure with resistance in the integrase inhibitor group compared with three participants ([1%]; all Met184Val/Ile) in the protease inhibitor group. 19 women in the protease inhibitor group discontinued because of adverse events compared with five in the integrase inhibitor group. INTERPRETATION: WAVES shows that clinical trials of ART regimens in global and diverse populations of treatment-naive women are possible. The findings support guidelines recommending integrase inhibitor based regimens in first-line antiretroviral therapy. FUNDING: Gilead Sciences. PMID- 27562743 TI - Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non inferiority, phase 2/3 trial. AB - BACKGROUND: For HIV-1-infected young people facing lifelong antiretroviral therapy (ART), short cycle therapy with long-acting drugs offers potential for drug-free weekends, less toxicity, and better quality-of-life. We aimed to compare short cycle therapy (5 days on, 2 days off ART) versus continuous therapy (continuous ART). METHODS: In this open-label, non-inferiority trial (BREATHER), eligible participants were aged 8-24 years, were stable on first-line efavirenz with two nucleoside reverse transcriptase inhibitors, and had HIV-1 RNA viral load less than 50 copies per mL for 12 months or longer. Patients were randomly assigned (1:1) to remain on continuous therapy or change to short cycle therapy according to a computer-generated randomisation list, with permuted blocks of varying size, stratified by age and African versus non-African sites; the list was prepared by the trial statistician and randomisation was done via a web service accessed by site clinician or one of the three coordinating trials units. The primary outcome was the proportion of participants with confirmed viral load 50 copies per mL or higher at any time up to the 48 week assessment, estimated with the Kaplan-Meier method. The trial was powered to exclude a non-inferiority margin of 12%. Analyses were intention to treat. The trial was registered with EudraCT, number 2009-012947-40, ISRCTN, number 97755073, and CTA, number 27505/0005/001-0001. FINDINGS: Between April 1, 2011, and June 28, 2013, 199 participants from 11 countries worldwide were randomly assigned, 99 to the short cycle therapy and 100 to continuous therapy, and were followed up until the last patient reached 48 weeks. 105 (53%) were men, median age was 14 years (IQR 12 18), and median CD4 cell count was 735 cells per MUL (IQR 576-968). Six (6%) patients assigned to the short cycle therapy versus seven (7%) assigned to continuous therapy had confirmed viral load 50 copies per mL or higher (difference -1.2%, 90% CI -7.3 to 4.9, non-inferiority shown). 13 grade 3 or 4 events occurred in the short cycle therapy group and 14 in the continuous therapy group (p=0.89). Two ART-related adverse events (one gynaecomastia and one spontaneous abortion) occurred in the short cycle therapy group compared with 14 (p=0.02) in the continuous therapy group (five lipodystrophy, two gynaecomastia, one suicidal ideation, one dizziness, one headache and syncope, one spontaneous abortion, one neutropenia, and two raised transaminases). INTERPRETATION: Non inferiority of maintaining virological suppression in children, adolescents, and young adults was shown for short cycle therapy versus continous therapy at 48 weeks, with similar resistance and a better safety profile. This short cycle therapy strategy is a viable option for adherent HIV-infected young people who are stable on efavirenz-based ART. FUNDING: UK National Institute for Health Research Health Technology Assessment; UK Medical Research Council; European Commission; PENTA Foundation; INSERM SC10-US19, France. PMID- 27562744 TI - Sexual behaviours, HIV testing, and the proportion of men at risk of transmitting and acquiring HIV in London, UK, 2000-13: a serial cross-sectional study. AB - BACKGROUND: HIV incidence in men who have sex with men (MSM) in the UK has remained unchanged over the past decade despite increases in HIV testing and antiretroviral therapy (ART) coverage. In this study, we examine trends in sexual behaviours and HIV testing in MSM and explore the risk of transmitting and acquiring HIV. METHODS: In this serial cross-sectional study, we obtained data from ten cross-sectional surveys done between 2000 and 2013, consisting of anonymous self-administered questionnaires and oral HIV antibody testing in MSM recruited in gay social venues in London, UK. Data were collected between October and January for all survey years up to 2008 and between February and August thereafter. All men older than 16 years were eligible to take part and fieldworkers attempted to approach all MSM in each venue and recorded refusal rates. Data were collected on demographic and sexual behavioural characteristics. We analysed trends over time using linear, logistic, and quantile regression. FINDINGS: Of 13 861 questionnaires collected between 2000 and 2013, we excluded 1985 (124 had completed the survey previously or were heterosexual reporting no anal intercourse in the past year, and 1861 did not provide samples for antibody testing). Of the 11 876 eligible MSM recruited, 1512 (13%) were HIV positive, with no significant trend in HIV positivity over time. 35% (531 of 1505) of HIV positive MSM had undiagnosed infection, which decreased non-linearly over time from 34% (45 of 131) to 24% (25 of 106; p=0.01), while recent HIV testing (ie, in the past year) increased from 26% (263 of 997) to 60% (467 of 777; p<0.0001). The increase in recent testing in undiagnosed men (from 29% to 67%, p<0.0001) and HIV negative men (from 26% to 62%, p<0.0001) suggests that undiagnosed infection might increasingly be recently acquired infection. The proportion of MSM reporting unprotected anal intercourse (UAI) in the past year increased from 43% (513 of 1187) to 53% (394 of 749; p<0.0001) and serosorting (exclusively) increased from 18% (207 of 1132) to 28% (177 of 6369; p<0.0001). 268 (2%) of 11 570 participants had undiagnosed HIV and reported UAI in the past year were at risk of transmitting HIV. Additionally 259 (2%) had diagnosed infection and reported UAI and non-exclusive serosorting in the past year. Although we did not collect data on antiretroviral therapy or viral load, surveillance data suggests that a small proportion of men with diagnosed infection will have detectable viral load and hence might also be at risk of transmitting HIV. 2633 (25%) of 10 364 participants were at high risk of acquiring HIV (defined as HIV-negative MSM either reporting one or more casual UAI partners in the past year or not exclusively serosorting). The proportions of MSM at risk of transmission or acquisition changed little over time (p=0.96 for MSM potentially at risk of transmission and p=0.275 for MSM at high risk of acquiring HIV). Undiagnosed men reporting UAI and diagnosed men not exclusively serosorting had consistently higher partner numbers than did other MSM over the period (median ranged from one to three across surveys in undiagnosed men reporting UAI, two to ten in diagnosed men not exclusively serosorting, and none to two in other men). INTERPRETATION: An increasing proportion of undiagnosed HIV infections in MSM in London might have been recently acquired, which is when people are likely to be most infectious. High UAI partner numbers of MSM at risk of transmitting HIV and the absence of a significant decrease in the proportion of men at high risk of acquiring the infection might explain the sustained HIV incidence. Implementation of combination prevention interventions comprising both behavioural and biological interventions to reduce community-wide risk is crucial to move towards eradication of HIV. FUNDING: Public Health England. PMID- 27562746 TI - Building systems that change clinical practice and advance health sciences research. PMID- 27562745 TI - Optimum resource allocation to reduce HIV incidence across sub-Saharan Africa: a mathematical modelling study. AB - BACKGROUND: Advances in HIV prevention methods offer promise to accelerate declines in incidence, but how these methods can be deployed to have the best effect on the heterogeneous landscape and drivers of the pandemic remains unclear. We postulated that use of epidemic heterogeneity to inform the allocation of resources for combination HIV prevention could enhance the impact of HIV funding across sub-Saharan Africa. METHODS: We developed a compartmental mathematical model of HIV transmission and disease progression by risk group to subnational resolution in 18 countries, capturing 80% of the adult HIV burden in sub-Saharan Africa. Adults aged 15-49 years were grouped by risk of HIV acquisition and transmission, and those older than 50 years were assumed to have negligible risk. For each top-level administrative division, we calibrated the model to historical data for HIV prevalence, sexual behaviours, treatment scale up, and demographics. We then evaluated four strategies for allocation of prevention funding over a 15 year period from 2016 to 2030, which exploited epidemic differences between subnational regions to varying degrees. FINDINGS: For a $US20 billion representative expenditure over the 15 year period, scale-up of prevention along present funding channels could avert 5.3 million infections relative to no scale-up. Prioritisation of key populations could avert 3.7 million more infections than present funding channels, and additional prioritisation by within-country geography could avert 400 000 more infections. Removal of national constraints could avert a further 600 000 infections. Risk prioritisation has greater marginal impact than geographical prioritisation across multiple expenditure levels. However, targeting by both risk and geography is best for total impact and could achieve gains of up to three times more than present channels. A shift from the present pattern to the optimum pattern would rebalance resources towards more cost-effective interventions and emerging epidemics. INTERPRETATION: If domestic and international funders were to align strategically to build an aggregate funding pattern that is guided by the epidemiology of HIV, and particularly by the emerging understanding of local dynamics and epidemic drivers, more cost-effective and impactful HIV prevention investments could be achieved across sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation. PMID- 27562747 TI - Crafting the third century of the National Library of Medicine. PMID- 27562748 TI - Evidence-based public policy comes to Washington. PMID- 27562750 TI - [18F] Positron emission tomography response after rituximab-containing induction therapy in follicular lymphoma is an independent predictor of survival after adjustment for FLIPI in academic and community-based practice. AB - Positron emission tomography (PET) after induction therapy in follicular lymphoma (FL) is predictive of survival in clinical trials. We describe use of PET and computed tomography (CT) after rituximab-based induction therapy in FL patients followed by the National LymphoCare Study and explore the association between imaging response assessment and survival. Among 1289 patients, imaging consisted of: PET +/- CT (35%), CT alone (42%), other/no imaging (24%). Median follow-up was 7.6 years. In unadjusted analyses, positive PET +/- CT and CT were prognostic of inferior OS (HR 1.78; 95% CI: 1.16-2.72 and HR 1.61, 95% CI: 1.13-2.29, respectively) and PFS (HR 1.63, 95% CI: 1.21-2.20 and HR 1.45, 95% CI: 1.12-1.89, respectively). Adjusting for FL International Prognostic Index, PET remained predictive of OS (HR 1.54, 95% CI: 1.01-2.36) and PFS (HR 1.54, 95% CI: 1.14 2.07). Residual disease via PET in FL is prognostic of survival in clinical practice. PMID- 27562751 TI - An integrated lab-on-a-chip-based electrochemical biosensor for rapid and sensitive detection of cancer biomarkers. AB - Recent advances in the area of biosensor technology and microfluidic applications have enabled the miniaturisation of the sensing platforms. Here we describe a new integrated and fully automated lab-on-a-chip-based biosensor device prototype (MiSens) that has potential to be used for point-of-care cancer biomarker testing. The key features of the device include a new biochip, a device integrated microfluidic system and real-time amperometric measurements during the flow of enzyme substrate. For ease of use, a new plug and play type sensor chip docking station has been designed. This system allows the formation of an ~7 MUL capacity flow cell on the electrode array with the necessary microfluidic and electronic connections with one move of a handle. As a case study, the developed prototype has been utilised for the detection of prostate-specific antigen (PSA) level in serum that is routinely used as a biomarker for the diagnosis of prostate cancer. The patient samples from a nearby hospital have been collected and tested using the MiSens device, and the results have been compared to the hospital results. The obtained results indicate the potential of the MiSens device as a useful tool for point-of-care testing. Graphical abstract Microfluidics integrated and automated electrochemical biosensor device "MiSens" has been designed and fabricated by a multidisciplinary team and utilised to detect PSA from clinical samples. PMID- 27562749 TI - Animal NLRs provide structural insights into plant NLR function. AB - Background: The plant immune system employs intracellular NLRs (nucleotide binding [NB], leucine-rich repeat [LRR]/nucleotide-binding oligomerization domain [NOD]-like receptors) to detect effector proteins secreted into the plant cell by potential pathogens. Activated plant NLRs trigger a range of immune responses, collectively known as the hypersensitive response (HR), which culminates in death of the infected cell. Plant NLRs show structural and functional resemblance to animal NLRs involved in inflammatory and innate immune responses. Therefore, knowledge of the activation and regulation of animal NLRs can help us understand the mechanism of action of plant NLRs, and vice versa. Scope: This review provides an overview of the innate immune pathways in plants and animals, focusing on the available structural and biochemical information available for both plant and animal NLRs. We highlight the gap in knowledge between the animal and plant systems, in particular the lack of structural information for plant NLRs, with crystal structures only available for the N-terminal domains of plant NLRs and an integrated decoy domain, in contrast to the more complete structures available for animal NLRs. We assess the similarities and differences between plant and animal NLRs, and use the structural information on the animal NLR pair NAIP/NLRC4 to derive a plausible model for plant NLR activation. Conclusions: Signalling by cooperative assembly formation (SCAF) appears to operate in most innate immunity pathways, including plant and animal NLRs. Our proposed model of plant NLR activation includes three key steps: (1) initially, the NLR exists in an inactive auto-inhibited state; (2) a combination of binding by activating elicitor and ATP leads to a structural rearrangement of the NLR; and (3) signalling occurs through cooperative assembly of the resistosome. Further studies, structural and biochemical in particular, will be required to provide additional evidence for the different features of this model and shed light on the many existing variations, e.g. helper NLRs and NLRs containing integrated decoys. PMID- 27562752 TI - Improved specificity of serum phosphatidylcholine detection based on side-chain losses during negative electrospray ionization tandem mass spectrometry. AB - Many current tandem mass spectrometry (MS) methods for measuring phosphatidylcholines (PtdChos) rely only on precursor ion scanning of the common 184 m/z phosphocholine fragment with positive electrospray ionization (+ESI), and thus measure pools of PtdChos rather than specific isoforms. In this paper, we developed and compared an isotope dilution, tandem MS method capable of quantifying PtdChos based on specific fatty acid side-chains to the traditional 184 m/z method. The method is based on the detection of PtdCho ammonium formate (AmF) adduct as parent ions and fatty acid fragment daughter ions under negative electrospray ionization (-ESI). Accuracy, imprecision, and recovery were below 15 %, with acceptable linearity (R 2 > 0.99) up to 5 MUg/mL. We used the method to analyze the distributions of PtdChos with common side-chain combinations among 60 subjects and showed that it was possible for two individuals to have the same PtdCho pool concentration based on detection of the 184 m/z fragment, but up to a fourfold difference in the levels of specific isoforms comprising the pool based on our method. We then compared the results of both methods across 572 patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), or no impairment (NI), which showed that statistically significant associations between specific PtdCho isoforms and AD were masked with the 184 m/z method. Our findings demonstrate the importance of isoform specificity for quantifying PtdChos, and suggest caution when interpreting analytical data based on pools of biomarkers. PMID- 27562753 TI - Development of a novel ultrasonic-assisted magnetic dispersive solid-phase microextraction method coupled with high performance liquid chromatography for determination of mirtazapine and its metabolites in human urine and water samples employing experimental design. AB - Ultrasonic-assisted magnetic dispersive solid-phase microextraction coupled with high performance liquid chromatography has been developed for extraction and determination of mirtazapine, N-desmethyl mirtazapine, and 8-hydroxy mirtazapine in human urine and water samples. Magnetic graphene oxide-polyaniline nanocomposite (MGOPA) as a novel SPME sorbent was synthesized and used for the microextraction process. The analytical performance of MGOPA was compared with magnetic graphene oxide nanocomposite and indicated that the new sorbent was quite effective for extraction of mirtazapine, N-desmethyl mirtazapine, and 8 hydroxy mirtazapine. A two-stage experimental design approach, Plackett-Burman screening design and Box-Behnken optimization design, was used for screening and optimizing of significant variables in the microextraction process. The practical applicability of the proposed method was assessed by studying the linearity, intra-day and inter-day accuracy, enrichment factor, and precision. This method can be satisfactorily applied to the determination of mirtazapine and its metabolites in human urine and environmental water samples. Graphical Abstract Magnetic graphene oxide-polyaniline nanocomposite. PMID- 27562755 TI - Anatomy of cranial nerves in the first Turkish illustrated anatomy manuscript. PMID- 27562754 TI - Anti-inflammatory Effects of Phyllanthus emblica L on Benzopyrene-Induced Precancerous Lung Lesion by Regulating the IL-1beta/miR-101/Lin28B Signaling Pathway. AB - BACKGROUND: Phyllanthus emblica L (PEL), a well-known medical plant, has been used in Asian countries for a long time. Increasing evidence suggests that it can prevent the tumorigenesis of cancer associated with nonresolving inflammation. However, the possible anti-inflammatory mechanism responsible for preventing tumorigenesis of precancerous lung lesions is not well elucidated. MATERIALS AND METHODS: Male A/J mice were randomly divided into 5 groups with 10 mice in each group: (1) blank group (saline), (2) benzo(a)pyrene [B(a)P] group, (3) and (4) B(a)P + PEL (5 g/kg/d, 10 g/kg/d, administered by gavage), (5) B(a)P + celecoxib (30 mg/kg/d, administered by gavage). Nodes on the lung surface were observed and calculated. The levels of macrophage inflammatory protein (MIP-2), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-1beta were detected by enzyme-linked immunosorbent assay (ELISA) kits. Cyclo-oxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-alpha), IL-1beta, miR-101, and Lin28B protein levels were evaluated by immunohistochemistry and Western blotting. RESULTS: PEL extract treatment significantly reduced the number of nodes on the lung surface and attenuated B(a)P-induced levels of proinflammatory cytokines MIP-2, TNF alpha, IL-6, and IL-1beta in lung tissue. The protein expressions of COX-2 and HIF-alpha were significantly decreased by the treatment of PEL. In addition, both PEL extract and celecoxib markedly upregulate the expression of miR-101 while downregulating IL-1beta and Lin28B levels. CONCLUSION: Our study indicated that treatment with PEL extract can not only protect the lung from inflammatory injury but effectively prevent precancerous lung lesions through regulating the IL 1beta/miR-i101/Lin28B signaling pathway. PMID- 27562756 TI - The Reliability and Validity of Prostate Cancer Fatalism Inventory in Turkish Language. AB - This study aimed to conduct the reliability and validity study of the Prostate Cancer Fatalism Inventory in Turkish language. The study carried out in methodological type and consisted of 171 men. The ages of the participants ranged between 40 and 82. The content validity index was determined to be 0.80, Kaiser Meyer-Olkin value 0.825, Bartlett's test X 2 = 750.779 and p = 0.000. Then the principal component analysis was applied to the 15-item inventory. The inventory consisted of one dimension, and the load factors were over 0.30 for all items. The explained variance of the inventory was found 33.3 %. The Kuder-Richardson-20 coefficient was determined to be 0.849 and the item-total correlations ranged between 0.335 and 0.627. The Prostate Cancer Fatalism Inventory was a reliable and valid measurement tool in Turkish language. Integrating psychological strategies for prostate cancer screening may be required to strengthen the positive effects of nursing education. PMID- 27562757 TI - Enhancing Sense of Coherence and Mindfulness in an Ecclesiastical, Intercultural Group Training Context. AB - Sense of coherence (SOC) and mindfulness (MI) are believed to promote the health and well-being of individuals and organisations. The aim of this longitudinal study was to contribute to the literature on the development of SOC through training and interventions and thereby explore the development of these constructs in a group of senior professionals in the German Catholic Church. A sample of eight participants voluntarily enrolled for a 12-day training programme spread over a period of nine months to develop intercultural and inter-religious competencies, SOC and MI. Quantitative scores of the pre- and post-test SOC and MI questionnaires were qualitatively analysed. Results indicate that the majority of participants scored lower in the post-test on SOC and slightly higher in MI. The discussion explores the pitfalls in the development of these constructs in the study's participants and highlights the implications for theory and practice. Practical training implications for developing SOC and MI are offered. PMID- 27562758 TI - Bioresorbable vascular scaffold fracture in the overlapping zone as cause of accelerated neoatherosclerosis and in-scaffold very-late thrombosis. PMID- 27562759 TI - Identification of candidate miRNAs and expression profile of yak oocytes before and after in vitro maturation by high-throughput sequencing. AB - Small RNA represents several unique non-coding RNA classes that have important function in a wide range of biological processes including development of germ cells and early embryonic, cell differentiation, cell proliferation and apoptosis in diverse organisms. However, little is known about their expression profiles and effects in yak oocytes maturation and early development. To investigate the function of small RNAs in the maturation process of yak oocyte and early development, two small RNA libraries of oocytes were constructed from germinal vesicle stage (GV) and maturation in vitro to metaphase II-arrested stage (M II) and then sequenced using small RNA high-throughput sequencing technology. A total of 9,742,592 and 12,168,523 clean reads were obtained from GV and M II oocytes, respectively. In total, 801 and 1,018 known miRNAs were acquired from GV and M II oocytes, and 75 miRNAs were found to be significantly differentially expressed: 47 miRNAs were upregulated and 28 miRNAs were downregulated in the M II oocytes compared to the GV stage. Among the upregulated miRNAs, miR-342 has the largest fold change (9.25-fold). Six highly expressed miRNAs (let-7i, miR-10b, miR-10c, miR-143, miR-146b and miR-148) were validated by real-time quantitative PCR (RT qPCR) and consistent with the sequencing results. Furthermore, the expression patterns of two miRNAs and their potential targets were analysed in different developmental stages of oocytes and early embryos. This study provides the first miRNA profile in the mature process of yak oocyte. Seventy-five miRNAs are expressed differentially in GV and M II oocytes as well as among different development stages of early embryos, suggesting miRNAs involved in regulating oocyte maturation and early development of yak. These results showed specific miRNAs in yak oocytes had dynamic changes during meiosis. Further functional and mechanistic studies on the miRNAs during meiosis may beneficial to understanding the role of miRNAs on meiotic division. PMID- 27562760 TI - People adopt optimal policies in simple decision-making, after practice and guidance. AB - Organisms making repeated simple decisions are faced with a tradeoff between urgent and cautious strategies. While animals can adopt a statistically optimal policy for this tradeoff, findings about human decision-makers have been mixed. Some studies have shown that people can optimize this "speed-accuracy tradeoff", while others have identified a systematic bias towards excessive caution. These issues have driven theoretical development and spurred debate about the nature of human decision-making. We investigated a potential resolution to the debate, based on two factors that routinely differ between human and animal studies of decision-making: the effects of practice, and of longer-term feedback. Our study replicated the finding that most people, by default, are overly cautious. When given both practice and detailed feedback, people moved rapidly towards the optimal policy, with many participants reaching optimality with less than 1 h of practice. Our findings have theoretical implications for cognitive and neural models of simple decision-making, as well as methodological implications. PMID- 27562761 TI - Confirming the appearance of excess success: Reply to van Boxtel and Koch (2016). AB - van Boxtel and Koch (Psychonomic Bulletin & Review. doi: 10.3758/s13423-016-1010 0 , 2016) reported finding problems in the Test for Excess Success (TES) analysis in Francis (Psychonomic Bulletin & Review, 21, 1180-1187, 2014). They argued that their findings undermined the general analysis and the conclusions of the specific TES analysis for their article (van Boxtel & Koch in Psychological Science, 23(4), 410-418, 2012). As shown in this paper, their reported problems reflect misunderstandings about both the general properties of a TES analysis and how it was applied to their specific set of findings. Another look at the findings and theoretical claims in van Boxtel and Koch (Psychological Science, 23(4), 410-418, 2012) confirms the appearance of excess success. PMID- 27562762 TI - Estimating valence from the sound of a word: Computational, experimental, and cross-linguistic evidence. AB - It is assumed linguistic symbols must be grounded in perceptual information to attain meaning, because the sound of a word in a language has an arbitrary relation with its referent. This paper demonstrates that a strong arbitrariness claim should be reconsidered. In a computational study, we showed that one phonological feature (nasals in the beginning of a word) predicted negative valence in three European languages (English, Dutch, and German) and positive valence in Chinese. In three experiments, we tested whether participants used this feature in estimating the valence of a word. In Experiment 1, Chinese and Dutch participants rated the valence of written valence-neutral words, with Chinese participants rating the nasal-first neutral-valence words more positive and the Dutch participants rating nasal-first neutral-valence words more negative. In Experiment 2, Chinese (and Dutch) participants rated the valence of Dutch (and Chinese) written valence-neutral words without being able to understand the meaning of these words. The patterns replicated the valence patterns from Experiment 1. When the written words from Experiment 2 were transformed into spoken words, results in Experiment 3 again showed that participants estimated the valence of words on the basis of the sound of the word. The computational study and psycholinguistic experiments indicated that language users can bootstrap meaning from the sound of a word. PMID- 27562763 TI - McGurk stimuli for the investigation of multisensory integration in cochlear implant users: The Oldenburg Audio Visual Speech Stimuli (OLAVS). AB - The concurrent presentation of different auditory and visual syllables may result in the perception of a third syllable, reflecting an illusory fusion of visual and auditory information. This well-known McGurk effect is frequently used for the study of audio-visual integration. Recently, it was shown that the McGurk effect is strongly stimulus-dependent, which complicates comparisons across perceivers and inferences across studies. To overcome this limitation, we developed the freely available Oldenburg audio-visual speech stimuli (OLAVS), consisting of 8 different talkers and 12 different syllable combinations. The quality of the OLAVS set was evaluated with 24 normal-hearing subjects. All 96 stimuli were characterized based on their stimulus disparity, which was obtained from a probabilistic model (cf. Magnotti & Beauchamp, 2015). Moreover, the McGurk effect was studied in eight adult cochlear implant (CI) users. By applying the individual, stimulus-independent parameters of the probabilistic model, the predicted effect of stronger audio-visual integration in CI users could be confirmed, demonstrating the validity of the new stimulus material. PMID- 27562764 TI - Using parameter space partitioning to evaluate a model's qualitative fit. AB - Parameter space partitioning (PSP) is a versatile tool for model analysis that detects the qualitatively distinctive data patterns a model can generate, and partitions a model's parameter space into regions corresponding to these patterns. In this paper, we propose a PSP fit measure that summarizes the outcome of a PSP analysis into a single number, which can be used for model selection. In contrast to traditional model selection methods, PSP-based model selection focuses on qualitative data. We demonstrate PSP-based model selection by use of application examples in the area of category learning. A large-scale model recovery study reveals excellent recovery properties, suggesting that PSP fit is useful for model selection. PMID- 27562766 TI - Preparing for when things go wrong. PMID- 27562765 TI - A clinical evaluation of renal amyloidosis in the Japan renal biopsy registry: a cross-sectional study. AB - BACKGROUND AND AIM: The available clinical data are limited in a rare glomerular disease, renal amyloidosis. We aimed to clarify the clinical features of renal amyloidosis from database of the Japan Renal Biopsy Registry (J-RBR). METHODS: We performed a cross-sectional study with database of the J-RBR of the Japanese Society of Nephrology. We identified 281 cases of renal amyloidosis from 20,997 cases enrolled into the J-RBR from 2007 to 2014. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were compared among the levels of ages, amount of urine protein excretion (AUPE) or CKD G stages. RESULTS: The prevalence of renal amyloidosis was 1.3 % (281/20,997). DBP significantly decreased in higher age quartiles (P = 0.034). SBP and DBP did not increase in the progression of AUPE levels and CKD G stages. In multiple regression analysis, eGFR was a significant independent factor for SBP in all cases and a subgroup without hypertensive agents. There was a reverse significant relationship between SBP and eGFR. CONCLUSION: Blood pressure did not significantly increase in elderly and much proteinuric condition in renal amyloidosis. The progression of CKD and decrease of eGFR did not produce the higher SBP. The mechanism underlying these results remains unclear; however, they are unique features of renal amyloidosis. The couple of hypotensive and hypertensive conditions might produce no relationship between blood pressure and CKD stages. PMID- 27562767 TI - Sphingobacterium chuzhouense sp. nov., isolated from farmland soil. AB - A novel Gram-staining-negative bacterium, designated DH-5T, was isolated from a farmland soil in Chuzhou, Anhui province, China. Cells of strain DH-5T were aerobic, non-motile, non-spore-forming and rod-shaped. The organism grew at 20-37 degrees C, pH 6.0-9.0 and with 0-5 % NaCl (w/v). The DNA G+C content was 42.8 mol%. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), iso-C17 : 0 3-OH and C16 : 0. The respiratory quinone was MK-7, and the major polar lipids were phosphatidylethanolamine and phosphoglycolipid. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain DH-5T was a member of the genus Sphingobacterium and shared the highest similarity with Sphingobacterium gobiense H7T (96.0 %), followed by Sphingobacterium arenae H-12T (94.5 %). Strain DH-5T exhibited low DNA-DNA relatedness with S. gobiense H7T (35.1+/-1.4 %) and S. arenae H-12T (21.4+/-1.0 %). On the basis of phenotypic, genotypic and phylogenetic evidence, DH-5T is considered to represent a novel species of the genus Sphingobacterium, for which the name Sphingobacterium chuzhouense sp. nov. is proposed. The type strain is DH 5T (=ACCC 19856T=KCTC 42746T). PMID- 27562768 TI - The utility of quantitative ADC values for differentiating high-risk from low risk prostate cancer: a systematic review and meta-analysis. AB - PURPOSE: The purpose of the study is to perform a meta-analysis of studies investigating the diagnostic performance of apparent diffusion coefficient (ADC) values in separating high-risk from low-risk prostate cancer (PCa). METHODS: MEDLINE and EMBASE databases were searched in December 2015 for studies reporting diagnostic performance of ADC values for discriminating high-risk from low-risk PCa and providing sufficient data to construct 2 * 2 contingency tables. Diagnostic performance was quantitatively pooled using a bivariate random-effects model including subgroup analysis and assessment of study heterogeneity and methodological quality. RESULTS: 13 studies were included, providing 1107 tumor foci in 705 patients. Heterogeneity among studies was moderate (tau2 = 0.222). Overall sensitivity was 76.9% (95% CI 68.6-83.6%); overall specificity was 77.0% (95% CI 69.9-82.8%); and summary AUC was 0.67. Inverse correlation between sensitivity and specificity (rho = -0.58) indicated interstudy heterogeneity was partly due to variation in threshold for test positivity. Primary biases were readers' knowledge of Gleason score during ADC measurement, lack of prespecified ADC thresholds, and lack of prostatectomy as reference in some studies. Higher sensitivity was seen in studies published within the past 2 years and studies not using b value of at least 2000; higher specificity was associated with involvement of one, rather than two, readers measuring ADC. Field strength, coil selection, and advanced diffusion metrics did not significantly impact diagnostic performance. CONCLUSION: ADC values show moderate accuracy in separating high risk from low-risk PCa, although important biases may overestimate performance and unexplained sources of heterogeneity likely exist. Further studies using a standardized methodology and addressing identified weaknesses may help guide the use of ADC values for clinical decision-making. PMID- 27562770 TI - Psychological Distance Moderates the Amplification of Shared Experience. AB - Sharing an experience with another person can amplify that experience. Here, we propose for the first time that amplification is moderated by the psychological distance between co-experiencers. We predicted that experiences would be amplified for co-experiencers who are psychologically proximate but not for co experiencers who are psychologically distant. In two studies we manipulated both (a) whether or not a pleasant experience was shared and (b) the psychological distance between co-experiencers, via social distance (Study 1) and spatial distance (Study 2). In Study 1, co-experiencers either were unacquainted (i.e., strangers, socially distant) or became acquainted in the laboratory (i.e., socially proximate). In Study 2, co-experiencers were either in different rooms (i.e., spatially distant) or in the same room (i.e., spatially proximate). In both studies, the pleasant experience was amplified when shared compared with when not shared, but only when co-experiencers were psychologically proximate (vs. distant) to one another. PMID- 27562769 TI - Atherosclerotic Cardiovascular Disease and Anti-Retroviral Therapy. AB - In the current era of available therapy for human immunodeficiency virus (HIV), life expectancy for persons living with HIV (PLWH) nears that of the general population. Atherosclerotic cardiovascular disease (ASCVD) has become a particular burden for PLWH and society at large. PLWH have historically been shown to have an excess of cardiovascular risk and subsequent events when compared to the general population. Potential explanations include the increased prevalence of traditional risk factors, direct inflammatory and immunological effects from the HIV virus itself, and metabolic adverse effects of anti retroviral therapy (ART). Over the past few years, there has been building evidence that chronic inflammation and immune activation independent of virologic suppression contribute significantly to excess ASCVD risk. Although independent agents and combination therapies have varying metabolic effects, the evidence from major randomized controlled trials (RCTs) supports the benefits of early initiation of ART. In this review, we will discuss the epidemiology of ASCVD in HIV-infected patients compared with the general population, give an overview of potential pathogenesis of high-risk plaque in HIV-infected patients, discuss different metabolic effects of individual anti-retrovirals, and discuss the limitations in current screening models for assessing cardiovascular disease (CVD) risk and future directions for treatment. PMID- 27562771 TI - Erratum to: The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach. PMID- 27562772 TI - Beneficial effects of increased lysozyme levels in Alzheimer's disease modelled in Drosophila melanogaster. AB - Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer's disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Abeta1-42 or AbetaPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Abeta1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Abeta1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Abeta1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Abeta1-42 , which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD. PMID- 27562773 TI - Can treatment with statins have a negative influence on the tolerance of mandibular advancement devices? AB - BACKGROUND: Statins are considered the most effective drugs used in the treatment of dyslipidemias. Some of their adverse effects are related to muscle problems. Myalgias produced by statins appear more often during exercise. Mandibular advancement devices (MAD) force the propulsory and elevatory musculature of the mandible to exercise by making the jaw move forward. The aim of this study is to evaluate the incidence of muscular side effects (referred, spontaneous, or under palpation pain, myofascial pain, mandibular rigidity and fatigue, tension and sensitivity of the masticatory muscles) in a group of patients with a diagnosis of obstructive sleep apnea being treated with MAD. METHODS: This was a prospective study, involving consecutively 104 patients with a diagnosis of OSAS, and who had begun treatment with a custom made oral device. Muscular side effects were collected by anamnesis (verbal request and questionnaires), psychological status and clinical assessment (manual muscle palpation in the masticatory and cervical muscle groups), before and during MAD treatment. RESULTS: Of the total sample, 22.1 % presented muscular side effects with the oral device. However, in patients taking statins, this percentage was 57.1 %, as opposed to 16.7 % of the non-statins patients (p < 0.001). The risk of suffering muscular alterations during oral device treatment is higher in statin patients (odds ratio 6.67, p = 0.002). CONCLUSION: Treatment with statins can give rise to the appearance of undesirable side effects among patients being treated with oral devices. PMID- 27562774 TI - Diverse macrophages polarization in tumor microenvironment. AB - Macrophages are traditional innate immune cells that play critical roles in the clearance of pathogens and the maintenance of tissue homeostasis. Accumulating evidence proves that macrophages affect cancer initiation and malignancy. Macrophages can be categorized into two extreme subsets, classically activated (M1) and alternatively activated (M2) macrophages based on their distinct functional abilities in response to microenvironmental stimuli. In a tumor microenvironment, tumor associated macrophages (TAMs) are considered to be of the polarized M2 phenotype that enhances tumor progression and represent a poor prognosis. Furthermore, TAMs enhance tumor angiogenesis, growth, metastasis, and immunosuppression by secreting a series of cytokines, chemokines, and proteases. The regulation of macrophage polarization is considered to be a potential future therapy for cancer management. PMID- 27562775 TI - In situ evidence for metabolic and chemical microdomains in the structured polymer matrix of bacterial microcolonies. AB - CLSM and fluorescent probes were applied to assess the structure, composition, metabolic activity and gradients within naturally occurring beta-proteobacteria microcolonies. Extracellular polymeric substances (EPS) as defined by lectin binding analyses had three regions: (i) cell associated, (ii) intercellular and (iii) an outer layer covering the entire colony. We assessed structural, microenvironmental and metabolic implications of this complex EPS structure. Permeability studies indicated that the outer two layers were permeable to 20 nm beads, intercellular EPS to <40 nm beads and the outer layer was permeable to <100 nm beads. Phosphatase activity occurred at the cell surface and associated polymer. Glucose oxidase activity was only detected inside the cells and the cell associated polymer. Rhodamine 123 suggested that activity was highest near the cell surface. The potential sensitive dye JC-1 concentrated within the outer EPS layer and the gradient was responsive to inhibition by KCN, dispersion using KCl and enhanced by addition of nutrients (nutrient broth). pH gradients occurred from the cell interior (pH 7) to the microcolony interior (pH 4+) with a gradient of increasing pH (pH 7+) to the colony exterior. The EPS provides a physical and chemical structuring mechanism forming microdomains that segregate extracellular activities at the microscale, possibly resulting in a microcolony with unitary structure and function. PMID- 27562776 TI - Distribution and activity of the anaerobic methanotrophic community in a nitrogen fertilized Italian paddy soil. AB - In order to mitigate methane emissions from paddy fields, it is important to understand the sources and sinks. Most paddy fields are heavily fertilized with nitrite and nitrate, which can be used as electron acceptors by anaerobic methanotrophs. Here we show that slurry incubations of Italian paddy field soil with nitrate and 13C-labelled methane have the potential for nitrate-dependent anaerobic oxidation of methane (79.9 nmol g-1dw d-1). Community analysis based on 16S rRNA amplicon sequencing and qPCR of the water-logged soil and the rhizosphere showed that anaerobic oxidation of methane-associated archaea (AAA), including Methanoperedens nitroreducens, comprised 9% (bulk soil) and 1% (rhizosphere) of all archaeal reads. The NC10 phylum bacteria made up less than 1% of all bacterial sequences. The phylogenetic analysis was complemented by qPCR showing that AAA ranged from 0.28 * 106 to 3.9 * 106 16S rRNA gene copies g-1dw in bulk soil and 0.27 * 106 to 2.8 * 106 in the rhizosphere. The abundance of NC10 phylum bacteria was an order of magnitude lower. Revisiting published diversity studies, we found that AAA have been detected, but not linked to methane oxidation, in several paddy fields. Our data suggest an important role of AAA in methane cycling in paddy fields. PMID- 27562777 TI - Factors influencing the reinforcing value of fruit and unhealthy snacks. AB - OBJECTIVE: The present study investigated the reinforcing value of healthy and unhealthy snack food in adolescents (n = 108, aged 14-16 years). Moderation by access to different foods, sex and the personality trait reward sensitivity is tested. METHODS: In a computerized Food Reinforcement Task, adolescents could earn portions of a healthy and an unhealthy snack following an identical progressive reinforcement schedule for both food types. Reinforcing value of food was indexed by the number of button presses for each food type. Participants were allocated randomly to two-order condition: fruit-snack versus snack-fruit. Reward sensitivity was assessed with the Dutch age-downward version of Carver and White's BIS/BAS scale. RESULTS: Results showed that the reinforcing value of an unhealthy snack is higher than that of fruit, with participants making more button presses for unhealthy snacks, M = 1280.40, SD = 1203.53, than for fruit, M = 488.04, SD = 401.45, F(1,48) = 25.37, p < 0.001. This effect is stronger in boys (beta = -1367.67) than in girls (beta = -548.61). The effect is only present in the snack-fruit condition, not in the fruit-snack condition, indicating that access to food moderates the effect of food type. There is no evidence for moderation by reward sensitivity. CONCLUSIONS: Results point to the importance of simultaneously increasing barriers to obtain unhealthy food and promoting access to healthy food in order to facilitate healthy food choices. PMID- 27562779 TI - Local morphology informs location of activation during navigation within the parahippocampal region of the human brain. AB - The relationship between the local morphological features that define the entorhinal and parahippocampal cortex in the medial temporal region of the human brain and activation as measured during a navigation task with functional magnetic resonance imaging was examined individually in healthy participants. Two functional activation clusters were identified one within the caudal end of the collateral sulcus proper and the other in the parahippocampal extension of the collateral sulcus, clearly establishing the activation in the posterior parahippocampal cortex. A third activation cluster was identified where the anterior segment of the collateral sulcus proper gives way to the posterior segment, demonstrating also activation within the middle parahippocampal cortex. No activation was observed in the entorhinal cortex that lies medial to the rhinal sulcus or in the anterior part of the parahippocampal cortex along the anterior branch of the collateral sulcus proper. The activations could also be clearly differentiated from the cortex of the fusiform and lingual gyri that lie laterally and posteriorly. These findings demonstrated specific activation in the middle and posterior part of the parahippocampal cortex when information necessary for navigation was retrieved from a previously established cognitive map and demonstrate that the sulci that comprise the collateral sulcal complex represent important landmarks that can provide an accurate localization of activation foci along the parahippocampal cortex and allow identification of subdivisions involved in the processing of spatial information. PMID- 27562778 TI - Trimethylamine-N-oxide and its biological variations in vegetarians. AB - PURPOSE: Restriction of animal foods and choline may affect plasma trimethylamine N-oxide (TMAO). In vegetarians, we investigated the association between TMAO concentrations and the strictness of the diet or sex. We also studied the biological variations of TMAO in vegans. METHODS: Concentrations of plasma TMAO and choline metabolites were measured in 38 vegans and 67 lacto-ovo-vegetarians (group 1: mean age +/- SD = 50 +/- 15 years). Group 2 consisted of 66 vegans (29.2 +/- 7.3 years) that was tested twice within 3 months of intervention with vitamin B12 or a placebo. RESULTS: In group 1, plasma TMAO did not differ according to the strictness of the diet (both means 3.7 umol/L). In lacto-ovo vegetarians, men had higher TMAO and betaine, but lower trimethylamine than women. In group 2, the intervention with vitamin B12 had no effect on plasma TMAO or choline metabolites. The mean within-subject change of TMAO within 3 months was -0.3 (95 % confidence intervals = -0.7-0.1 umol/L). TMAO increased after 3 months (mean 1.7 to 2.8 umol/L) in vegans with a lower baseline dimethylglycine (2.2 umol/L), while it declined (from 2.7 to 1.9 umol/L) in vegans with a higher dimethylglycine (3.1 umol/L). The intra-class correlation coefficients were 0.819 for TMAO, 0.885 for betaine and 0.860 for dimethylglycine. CONCLUSIONS: Plasma TMAO was not related to the strictness of the vegetarian diet. Metabolisms of TMAO and dimethylglycine are interrelated. Intra-individual variations of TMAO are low in vegans. Changes of fasting plasma TMAO >80 % upon retesting are likely to exceed the biological variations. PMID- 27562780 TI - Halopiger thermotolerans sp. nov., a thermo-tolerant haloarchaeon isolated from commercial salt. AB - Three thermo-tolerant halophilic archaeal strains, SR-441T, SR-412 and SR-188, were isolated from commercial salt samples. Cells were non-motile pleomorphic rod shaped, and stained Gram-negative. Colonies were pink-pigmented. The three strains were able to grow with 1.7-4.6 M NaCl (optimum, 2.5 M), at pH 6.5-9.0 (optimum, pH 8.0) and at 35-60 degrees C (optimum, 45 degrees C). The orthologous 16S rRNA gene sequence similarities amongst the three strains were 98.8-99.3 %, and the level of DNA-DNA relatedness was 71-74 and 72-75 % (reciprocally). The closest relative was Halopiger aswanensis JCM 11628T with 98.6 %-99.1 % similarity in the orthologous 16S rRNA gene sequences, followed by two more Halopiger species, Halopiger xanaduensis JCM 14033T (98.5 %-99.1 %) and Halopiger salifodinae JCM 9578T (95.5 %-95.6 %). DNA-DNA relatednesses between the three strains and H. aswanensis JCM 11628T and H. xanaduensis JCM 14033T were 61 and 54 %, respectively. The polar lipids of the three novel strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, and bis sulfated diglycosyl archaeol-1. The most distinctive feature of the three strains was the ability to grow at 60 degrees C, while the maximum growth temperature of H. aswanensis is 55 degrees C. Based on phenotypic and phylogenetic analyses, the isolates are considered to represent a novel species of the genus Halopiger, for which the name Halopiger thermotolerans sp. nov. is proposed. The type strain is SR-441T (=JCM 19583T=KCTC 4248T) isolated from solar salt produced in Australia. SR-412 (=JCM 19582) and SR-188 (=JCM 19581) isolated from commercial salt samples are additional strains of the species. PMID- 27562781 TI - Two years of sunshine: has openness about payments reduced industry influence in healthcare? PMID- 27562782 TI - Imaging of Headache in Pregnancy. AB - Pregnant women are most likely to have primary headaches, such as migraine and tension-type headaches, which can be diagnosed and treated without brain imaging. Primary headaches may even start de novo during pregnancy, especially in the first few months. However, when the headache occurs late in pregnancy or in the peripartum period, secondary causes of headaches need to be considered and evaluated by brain and/or vascular imaging, generally using magnetic resonance techniques. There is considerable overlap between the cerebrovascular complications of pregnancy, including preeclampsia/eclampsia, posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), and both hemorrhagic and ischemic strokes; although, their imaging may be distinctive. Imaging is necessary to distinguish between arterial and venous pathology causing headache in the peripartum patient, as there can be similar presenting symptoms. Mass lesions, both neoplastic and inflammatory, can enlarge and produce headaches and neurological symptoms late in pregnancy. PMID- 27562784 TI - Expression of cell polarity protein scribble differently affects prognosis in primary tumor and lymph node metastasis of breast cancer patients. AB - BACKGROUND: We evaluated the relationship between the immunohistochemically determined expression of the cell polarity protein scribble to prognosis in different environments of estrogen receptor (ER) expression and epithelial-to mesenchymal transition (EMT). METHODS: We immunohistochemically evaluated the expression level of scribble in primary tumors and lymph node metastases of 225 node-positive breast cancer patients who had received chemotherapy. We then evaluated metastasis-free survival (MFS) in the absence or presence of ER and the EMT-related protein vimentin. RESULTS: Among patients with ER-positive tumors, patients with low scribble expression in the primary tumor had a significantly shorter MFS than patients with high scribble expression (p = 0.0225). Furthermore, among patients with vimentin-negative tumors, patients with low expression of scribble in the primary tumor had significantly shorter MFS than patients with high expression of scribble (p = 0.0463). In contrast, among patients with vimentin-positive tumors, patients with high expression of scribble in the primary tumor had significantly shorter MFS than patients with low expression of scribble (p = 0.0343). Moreover, among patients with ER-negative tumors, patients with high expression of scribble in lymph node metastases showed significantly higher expression of E-cadherin in metastases (p = 0.0407) and had significantly shorter MFS than patients with low expression of scribble (p = 0.0064). CONCLUSIONS: The prognostic significance of cell polarity depended on the ER expression and EMT. Furthermore, the preservation of cell polarity in metastases was associated with mesenchymal-to-epithelial transition and worse prognosis. Cell polarity promotes the diversity of metastasis in combination with malignancy grade in breast cancer patients. PMID- 27562783 TI - beta-1,3-Glucans are components of brown seaweed (Phaeophyceae) cell walls. AB - LAMP is a cell wall-directed monoclonal antibody (mAb) that recognizes a beta (1,3)-glucan epitope. It has primarily been used in the immunolocalization of callose in vascular plant cell wall research. It was generated against a brown seaweed storage polysaccharide, laminarin, although it has not often been applied in algal research. We conducted in vitro (glycome profiling of cell wall extracts) and in situ (immunolabeling of sections) studies on the brown seaweeds Fucus vesiculosus (Fucales) and Laminaria digitata (Laminariales). Although glycome profiling did not give a positive signal with the LAMP mAb, this antibody clearly detected the presence of the beta-(1,3)-glucan in situ, showing that this epitope is a constituent of these brown algal cell walls. In F. vesiculosus, the beta-(1,3)-glucan epitope was present throughout the cell walls in all thallus parts; in L. digitata, the epitope was restricted to the sieve plates of the conductive elements. The sieve plate walls also stained with aniline blue, a fluorochrome used as a probe for callose. Enzymatic digestion with an endo-beta (1,3)-glucanase removed the ability of the LAMP mAb to label the cell walls. Thus, beta-(1,3)-glucans are structural polysaccharides of F. vesiculosus cell walls and are integral components of the sieve plates in these brown seaweeds, reminiscent of plant callose. PMID- 27562785 TI - Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO). AB - BACKGROUND AND OBJECTIVE: The hypoxia PET tracer, 1-[18F]fluoro-3-(2-nitro 1Himidazol- 1-yl)-propan-2-ol ([18F]FMISO) is the first radiotracer developed for hypoxia PET imaging and has shown promising for cancer diagnosis and prognosis. However, access to [18F]FMISO radiotracer is limited due to the needed cyclotron and radiochemistry expertise. The study aimed to develop the automated production method on the [18F]FMISO radiotracer with the novel fully automated platform of the BG75 system and validate its usage on animal tumor models. METHOD: [18F]FMISO was produced with the dose synthesis cartridge automatically on the BG75 system. Validation of [18F]FMISO hypoxia imaging functionality was conducted on two tumor mouse models (FaDu/U87 tumor). The distribution of [18F]FMISO within tumor was further validated by the standard hypoxia marker EF5. RESULTS: The average radiochemical purity was (99+/-1) % and the average pH was 5.5+/-0.2 with other quality attributes passing standard criteria (n=12). Overall biodistribution for [18F]FMISO in both tumor models was consistent with reported studies where bladder and large intestines presented highest activity at 90 min post injection. High spatial correlation was found between [18F]FMISO autoradiography and EF5 hypoxia staining, indicating high hypoxia specificity of [18MF]FMISO. CONCLUSION: This study shows that qualified [18F]FMISO can be efficiently produced on the BG75 system in an automated "dose-on-demand" mode using single dose disposable cards. The possibilities of having a low-cost, automated system manufacturing ([18F]Fluoride production + synthesis + QC) different radiotracers will greatly enhance the potential for PET technology to reach new geographical areas and underserved patient populations. PMID- 27562786 TI - Pearls: Snakes in the Grass and Other Surgical Gems. PMID- 27562787 TI - Surgical Risks and Costs of Care are Greater in Patients Who Are Super Obese and Undergoing THA. AB - BACKGROUND: Patients with morbid obesity, defined as a BMI greater than 40 kg/m2, and super obesity, defined as a BMI greater than 50 kg/m2, increasingly present for total hip replacement. There is disagreement in the literature whether these individuals have greater surgical risks and costs for the episode of care, and the magnitude of those risks and costs. There also is no established threshold for obesity as defined by BMI in identifying increased complications, risks, and costs of care. Until recently, analysis of higher BMI data was limited to small cohorts from hospital-based data banks, based on BMI or height and weight only, often as part of a multivariate analysis. On October 1, 2010 the Centers for Medicare & Medicaid Services added a fifth digit to the BMI data, V85.xx, in the Medicare data bank, which allowed data mining of cases of patients with higher BMI. To our knowledge, our study is the first large retrospective Medicare data mining study, which allows us to examine BMI levels greater than 40 and 50 kg/m2 to delineate risks, complications, and costs for these patients. QUESTIONS/PURPOSES: We sought to quantify (1) the surgical risk, and (2) the costs associated with complications after THA in patients who were morbidly obesity (BMI >= 40 kg/m2) or super obese (BMI >= 50 kg/m2). METHODS: This is a retrospective study of patients, using Medicare hospital claims data, who underwent THA. The ICD-9 Clinical Modification (CM) diagnosis code V85.4x was used to identify patients with morbid obesity and with super obesity from October 1, 2010 through December 31, 2014. Patients without any BMI-related diagnosis codes were used as the control group. Twelve complications occurring during the 90 days after THA were analyzed using multivariate Cox models adjusting for patient demographic, comorbidities, and institutional factors. In addition, hospital charges and payments were compared from primary surgery through the subsequent 90 days. RESULTS: Patients with morbid obesity had increased postoperative complications including prosthetic joint infection (hazard ratio [HR], 3.71; 95% CI, 3.2-4.31; p < 0.001), revision (HR, 1.91; 95% CI, 1.69-2.16; p < 0.001), and wound dehiscence (HR, 3.91; 95% CI, 3.14-4.86; p < 0.001). In addition, patients with morbid obesity had increased risk of deep vein thrombosis (HR, 1.43; 95% CI, 1.14-1.79; p < 0.002), pulmonary embolism (HR, 1.57; 95% CI, 1.25-1.99; p < 0.001), implant failure (HR, 1.48; 95% CI, 1.3-1.68; p < 0.001), acute renal failure (HR, 1.68; 95% CI, 1.56-1.80; p < 0.001), and all-cause readmission (HR, 1.48; 95% CI, 1.40-1.56; p < 0.001). However, death (HR, 0.94 95% CI, 0.73-1.19 p < 0.592), acute myocardial infarction (HR, 0.94; 95% CI, 0.74 1.2 p < 0.631), and dislocation (HR 1.07; 95% CI, 0.85-1.34; p < 0.585) were not different between patients in the control and morbidly obese groups. Super obese patients had an increased risk of infection (HR, 6.48; 95% CI, 4.54-9.25; p < 0.001), wound dehiscence (HR, 9.81; 95% CI, 6.31-15.24; p < 0.001), and readmission (HR, 2.16; 95% CI, 1.84-2.54; p < 0.001) compared with patients with normal BMI. Controlling for patient and institutional factors, each THA had mean total hospital charges of USD 88,419 among patients who were super obese compared with USD 73,827 for the control group, a difference of USD 14,591. Medicare payment for the patients who were super obese also was higher, but only by USD 3631. CONCLUSIONS: Patients who are super obese are at increased risk for serious complications compared with patients with morbid obesity, whose risks are elevated relative to patients whose BMI is less than 40 kg/m2. Costs of care for patients who were super obese, likewise, were increased. We present BMI outcomes to allow an objective basis for patient counseling, risk stratification, maintaining access to orthopaedic surgical care, and maintaining hospital operating margins. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27562788 TI - CORR Insights(r): Hips With Protrusio Acetabuli Are at Increased Risk for Failure After Femoroacetabular Impingement Surgery: A 10-year Followup. PMID- 27562789 TI - Letter to the Editor: Editor's Spotlight/Take 5: Physicians' Attire Influences Patients' Perceptions in the Urban Outpatient Orthopaedic Surgery Setting. PMID- 27562790 TI - ArtiFacts: Jean Louis Petit's Screw Tourniquet. PMID- 27562791 TI - Heuristic Description of Magnetoelectricity of Cu2OSeO3. AB - CuO2SeO3 is an insulating material that hosts topologically nontrivial spin whirls, so-called skyrmions, and exhibits magnetoelectric coupling allowing to manipulate these skyrmions by means of electric fields. We report magnetic force microscopy imaging of the real-space spin structure on the surface of a bulk single crystal of CuO2SeO3. Based on measurements of the electric polarization using Kelvin-probe force microscopy, we develop a heuristic description of the magnetoelectric properties in CuO2SeO3. The model successfully describes the dependency of the electric polarization on the magnetization in all magnetically modulated phases. PMID- 27562792 TI - Dietary methyl donors affect in vivo methionine partitioning between transmethylation and protein synthesis in the neonatal piglet. AB - Methionine metabolism is critical during development with significant requirements for protein synthesis and transmethylation reactions. However, separate requirements of methionine for protein synthesis and transmethylation are difficult to define because after transmethylation, demethylated methionine is either irreversibly oxidized to cysteine during transsulfuration, or methionine is regenerated by the dietary methyl donors, choline (via betaine) or folate during remethylation. We hypothesized that remethylation contributes significantly to methionine availability and affects partitioning between protein and transmethylation. 4-8-day-old neonatal piglets were fed a diet devoid (MD-) (n = 8) or replete (MS+) (n = 8) of folate, choline and betaine to limit remethylation. After 5 days, dietary methionine was reduced to 80 % of requirement in both groups of piglets to ensure methionine availability was limited. On day 7, an intragastric infusion of [13C1]methionine and [2H3 methyl]methionine was administered to measure methionine cycle flux. In MD- piglets, in vivo remethylation was 60 % lower despite 23-fold greater conversion of choline to betaine (P < 0.05) and transmethylation was 56 % lower (P < 0.05), suggesting dietary methyl donors spared 425 umol methyl/day for transmethylation. The priority of protein synthesis versus transmethylation was clear during MD- feeding (P < 0.05), as an additional 6 % of methionine flux was for protein synthesis in those piglets (P < 0.05). However, whole body transsulfuration was unaffected in vivo despite reduced in vitro cystathionine-beta-synthase capacity in MD- piglets (P < 0.05). Our data show that remethylation contributes significantly to methionine availability and that transmethylation is sacrificed to maintain protein synthesis when methionine is limiting in neonates, which should be considered when determining the methionine requirement. PMID- 27562794 TI - Transglutaminase-2: evolution from pedestrian protein to a promising therapeutic target. AB - The ability of cancer cells to metastasize represents the most devastating feature of cancer. Currently, there are no specific biomarkers or therapeutic targets that can be used to predict the risk or to treat metastatic cancer. Many recent reports have demonstrated elevated expression of transglutaminase 2 (TG2) in multiple drug-resistant and metastatic cancer cells. TG2 is a multifunctional protein mostly known for catalyzing Ca2+-dependent -acyl transferase reaction to form protein crosslinks. Besides this transamidase activity, many Ca2+ independent and non-enzymatic activities of TG2 have been identified. Both, the enzymatic and non-enzymatic activities of TG2 have been implicated in diverse pathophysiological processes such as wound healing, cell growth, cell survival, extracellular matrix modification, apoptosis, and autophagy. Tumors have been frequently referred to as 'wounds that never heal'. Based on the observation that TG2 plays an important role in wound healing and inflammation is known to facilitate cancer growth and progression, we discuss the evidence that TG2 can reprogram inflammatory signaling networks that play fundamental roles in cancer progression. TG2-regulated signaling bestows on cancer cells the ability to proliferate, to resist cell death, to invade, to reprogram glucose metabolism and to metastasize, the attributes that are considered important hallmarks of cancer. Therefore, inhibiting TG2 may offer a novel therapeutic approach for managing and treatment of metastatic cancer. Strategies to inhibit TG2-regulated pathways will also be discussed. PMID- 27562795 TI - Metastatic pleural mesothelioma presenting in a breast fine needle aspiration specimen. PMID- 27562793 TI - P2X7 receptor-mediated TG2 externalization: a link to inflammatory arthritis? AB - Transglutaminases have important roles in stabilizing extracellular protein assemblies in tissue repair processes but some reaction products can stimulate immune activation, leading to chronic inflammatory conditions or autoimmunity. Exacerbated disease in models of inflammatory arthritis has been ascribed to sustained extracellular enzyme activity alongside formation of select protein modifications. Here, we review the evidence, with a focus on the link between P2X7R signaling and TG2 export, a pathway that we have recently discovered which ties extracellular protein modifications into the danger signal-mediated innate immune response. These recent insights offer new opportunities for therapeutic intervention. PMID- 27562796 TI - Differential selection on pollen and pistil traits in relation to pollen competition in the context of a sexual conflict over timing of stigma receptivity. AB - Sexual conflict and its evolutionary consequences are understudied in plants, but the theory of sexual conflict may help explain how selection generates and maintains variability. Here, we investigated selection on pollen and pistil traits when pollen arrives sequentially to partially receptive pistils in relation to pollen competition and a sexual conflict over timing of stigma receptivity in the mixed-mating annual Collinsia heterophylla (Plantaginaceae). In this species the conflict is generated by early fertilizing pollen that reduces seed production, which is counteracted by delaying receptivity in the recipient. We performed sequential two-donor pollinations at early floral developmental stages involving two pollen deposition schedules (with or without a time lag of 1 day), using only outcross or self and outcross pollen. We investigated pollen and pistil traits in relation to siring success (male fitness) and seed production (female fitness). In contrast to previous findings in receptive pistils in C. heterophylla and in other species, last arriving pollen donors showed highest siring success in partially receptive pistils. The last male advantage was weaker when self pollen was the first arriving donor. Two measures of germination rate (early and late) and pollen tube growth rate of first arriving donors were important for siring success in crosses with a time lag, while only late germination rate had an effect in contemporary crosses. Curiously, late stigma receptivity was negatively related to seed production in our contemporary crosses, which was opposite to expectation. Our results in combination with previous studies suggest that pollen and pistil traits in C. heterophylla are differentially advantageous depending on stage of floral development and varying pollen deposition schedules. Variation in success of these traits over floral development time may result from sexually antagonistic selection. PMID- 27562797 TI - Predictors of Non-Attendance to the Postpartum Follow-up Visit. AB - Objectives This study aimed to measure the incidence and identify predictors of postpartum visit non-attendance, using medical records of women who received prenatal care and went on to deliver live births at Montefiore Hospital in 2013. Methods Pearson's Chi square tests were used to assess the association between maternal demographics, insurance status, and delivery information with non attendance of a postpartum visit. Logistic regression and modified Poisson regression models were then used to identify statistically significant predictors of postpartum visit non-attendance. Results We found that one-third of all women who attended a prenatal visit at Montefiore Hospital did not return for a postpartum visit. Variables significantly associated with non-attendance include having Medicaid or no insurance (RR 1.4, 95 % CI 1.2-1.6), being Hispanic or Latino (RR 1.2, 95 % CI 1.1-1.3), having a vaginal delivery (RR 1.2, 95 % CI 1.1 1.4), and age <20 years (RR 0.77, 95 % CI 0.64-0.92). Conclusions for Practice We conclude that the risk of postpartum visit non-attendance disproportionately impacts socially and economically vulnerable patients who are: younger, part of a minority ethnic background, and depend on state funded health insurance. Our results highlight the disparity in access to postpartum care and the importance of identifying barriers to attendance as well as developing creative strategies of providing postpartum care outside of the traditional postpartum visit framework. PMID- 27562798 TI - Maternal Health Risk Assessment and Behavioral Intervention in the NICU Setting Following Very Low Birth Weight Delivery. AB - Objectives To investigate whether maternal health risk assessment and behavioral intervention in the neonatal intensive care unit (NICU) improves women's health care seeking and health behaviors following the birth of a very low birth weight (VLBW) infant. Methods Using a quasi-experimental non-equivalent control group pretest/posttest design, 80 women who had given birth to a VLBW infant that was admitted to the NICU were enrolled into one of two cohorts: 40 into a 'Minimal Intervention' cohort, who received a single session risk assessment and health education pamphlets, and 40 into an 'Enhanced Intervention' cohort, who received five counseling sessions targeting identified risks. The proportion of women with specific health care seeking and health behaviors in the two cohorts were compared at baseline and 3- and 9-months post-intervention. Results Women in the Enhanced Intervention cohort were more likely to attend the postpartum visit (73 % vs. 48 %; p = 0.04), ingest folic acid daily (65 % vs. 19 %, p < 0.001), and correctly and consistently use a method of contraception (82 % vs. 63 %, p = 0.03) over the 9-month follow-up period. In multivariate analysis, the between cohort differences in daily folic acid use (aOR = 3.45, 95 % CI 1.61-7.40) and correct and consistent use of a method of contraception (aOR = 1.46, 95 % CI 1.05 2.06) remained statistically significant at 9-months and the reduction in risk of unintended pregnancy nearly achieved statistical significance (aOR = 0.62, 95 % CI 0.12-1.0). Conclusions for Practice This study provides support for the implementation of maternal risk assessment and behavioral intervention in the NICU setting to promote women's positive health care seeking and health behaviors. PMID- 27562799 TI - The Availability and Use of Postpartum LARC in Mexico and Among Hispanics in the United States. AB - Objectives In the 1980s, policy makers in Mexico led a national family planning initiative focused, in part, on postpartum IUD use. The transformative impact of this initiative is not well known, and is relevant to current efforts in the United States (US) to increase women's use of long-acting reversible contraception (LARC). Methods Using six nationally representative surveys, we illustrate the dramatic expansion of postpartum LARC in Mexico and compare recent estimates of LARC use immediately following delivery through 18 months postpartum to estimates from the US. We also examine unmet demand for postpartum LARC among 321 Mexican-origin women interviewed in a prospective study on postpartum contraception in Texas in 2012, and describe differences in the Mexican and US service environments using a case study with one of these women. Results Between 1987 and 2014, postpartum LARC use in Mexico doubled, increasing from 9 to 19 % immediately postpartum and from 13 to 26 % by 18 months following delivery. In the US, <0.1 % of women used an IUD or implant immediately following delivery and only 9 % used one of these methods at 18 months. Among postpartum Mexican-origin women in Texas, 52 % of women wanted to use a LARC method at 6 months following delivery, but only 8 % used one. The case study revealed provider and financial barriers to postpartum LARC use. Conclusions Some of the strategies used by Mexico's health authorities in the 1980s, including widespread training of physicians in immediate postpartum insertion of IUDs, could facilitate women's voluntary initiation of postpartum LARC in the US. PMID- 27562800 TI - The effect of temperature exposure during shipment on a commercially available demineralized bone matrix putty. AB - During August and September of 2013, temperature data loggers were shipped to and from an AATB accredited and FDA registered allograft tissue processing facility in Belgrade, MT (Bacterin International, Inc.) to five warm climate cities (Dallas, TX, El Paso, TX, New Orleans, LA, Phoenix, AZ, and Tampa, FL). Shipping data acquired from 72 independent shipments were analyzed to generate an assessment of temperature exposure, shipment times, and shipping event durations experienced during routine distribution. Overall the packages experienced an average temperature of 26.2 +/- 2.3 degrees C which mirrored the average external ambient temperature of 25.8 +/- 3.0 degrees C. However, temperature spikes above 40 degrees C were frequently observed. The data from the model shipments were extrapolated to provide a worst-case high temperature spike of 52.9 degrees C for 12 h and 14 min. Multiple lots of a commercially available demineralized bone matrix (DBM) putty (OsteoSelect(r) DBM Putty) were subjected to continuous heating at 50 degrees C, to multiple worst-case temperature spikes, and to multiple freeze-thaw cycles to assess the effects of these temperature extremes on the handling and osteoinductivity of the allograft tissue. Five weeks of continuous exposure to 50 degrees C and 12 simulated worst case one-way shipments did not adversely affect the handling characteristics or the in vivo osteoinductivity of the product. PMID- 27562801 TI - Identification of Signet Ring Cell Change in Colonic Subserosa in the Setting of Clostridium difficile Colitis. AB - Signet ring cell change of intestinal epithelial cells is a rare but well-known mimicker of signet ring cell carcinoma and is often associated with ischemic and/or pseudomembranous colitis. Instead, signet ring cell change involving nonepithelial cells in the subserosa of the intestine is an extremely rare finding with only a single case report in the literature to date. We report a new case of benign signet ring cell change localized in the subserosa of the large bowel incidentally identified in a resection specimen for Clostridium difficile colitis mimicking a metastatic signet ring cell carcinoma. Based on the morphologic features and immunohistochemical profile, we propose that these signet ring cells may possibly represent modified/degenerated fat cells. Furthermore, we discuss how to differentiate benign signet ring cells from a signet ring cell carcinoma. PMID- 27562802 TI - Assessment of lymphocyte proliferation for diagnostic purpose: Comparison of CFSE staining, Ki-67 expression and 3H-thymidine incorporation. AB - The capability of lymphocytes to respond to antigenic or mitogenic stimulation is an important feature in the diagnosis of various immunodeficiencies and immune disorders. We used large cohorts of both immune compromised patients and healthy controls to measure lymphocyte proliferations by means of three methods: CFSE staining, Ki-67 expression and 3H-thymidine incorporation. The advantages and disadvantages of each method was then evaluated for use in routine clinical diagnostic. The statistical analysis was performed between the outcomes and the correlation between all three methods was computed. CFSE and Ki-67 assay correlated well with the r=0.767, correlation between Ki-67 expression and 3H thymidine incorporation was 0.546 and correlation between CFSE staining and 3H thymidine incorporation was 0.337. The differences between these three methods concerning complexity, sensitivity and reliability as well as the financial aspects are discussed hereafter. CFSE and its analogues provide the cheapest and reasonable choice for measuring lymphocyte proliferation, while Ki-67 represents a more expensive, but more sensitive and robust method. The original 3H-thymidine assay does not bring any advantages and cannot compare to the competition presented by modern flow cytometric methods available today. PMID- 27562803 TI - The Binaural Interaction Component in Barn Owl (Tyto alba) Presents few Differences to Mammalian Data. AB - The auditory brainstem response (ABR) is an evoked potential that reflects the responses to sound by brainstem neural centers. The binaural interaction component (BIC) is obtained by subtracting the sum of the monaural ABR responses from the binaural response. Its latency and amplitude change in response to variations in binaural cues. The BIC is thus thought to reflect the activity of binaural nuclei and is used to non-invasively test binaural processing. However, any conclusions are limited by a lack of knowledge of the relevant processes at the level of individual neurons. The aim of this study was to characterize the ABR and BIC in the barn owl, an animal where the ITD-processing neural circuits are known in great detail. We recorded ABR responses to chirps and to 1 and 4 kHz tones from anesthetized barn owls. General characteristics of the barn owl ABR were similar to those observed in other bird species. The most prominent peak of the BIC was associated with nucleus laminaris and is thus likely to reflect the known processes of ITD computation in this nucleus. However, the properties of the BIC were very similar to previously published mammalian data and did not reveal any specific diagnostic features. For example, the polarity of the BIC was negative, which indicates a smaller response to binaural stimulation than predicted by the sum of monaural responses. This is contrary to previous predictions for an excitatory-excitatory system such as nucleus laminaris. Similarly, the change in BIC latency with varying ITD was not distinguishable from mammalian data. Contrary to previous predictions, this behavior appears unrelated to the known underlying neural delay-line circuitry. In conclusion, the generation of the BIC is currently inadequately understood and common assumptions about the BIC need to be reconsidered when interpreting such measurements. PMID- 27562804 TI - Symmetric Electrode Spanning Narrows the Excitation Patterns of Partial Tripolar Stimuli in Cochlear Implants. AB - In cochlear implants (CIs), standard partial tripolar (pTP) mode reduces current spread by returning a fraction of the current to two adjacent flanking electrodes within the cochlea. Symmetric electrode spanning (i.e., separating both the apical and basal return electrodes from the main electrode by one electrode) has been shown to increase the pitch of pTP stimuli, when the ratio of intracochlear return current was fixed. To explain the pitch increase caused by symmetric spanning in pTP mode, this study measured the electrical potentials of both standard and symmetrically spanned pTP stimuli on a main electrode EL8 in five CI ears using electrical field imaging (EFI). In addition, the spatial profiles of evoked compound action potentials (ECAP) and the psychophysical forward masking (PFM) patterns were also measured for both stimuli. The EFI, ECAP, and PFM patterns of a given stimulus differed in shape details, reflecting the different levels of auditory processing and different ratios of intracochlear return current across the measurement methods. Compared to the standard pTP stimuli, the symmetrically spanned pTP stimuli significantly reduced the areas under the curves of the normalized EFI and PFM patterns, without shifting the pattern peaks and centroids (both around EL8). The more focused excitation patterns with symmetric spanning may have caused the previously reported pitch increase, due to an interaction between pitch and timbre perception. Being able to reduce the spread of excitation, pTP mode symmetric spanning is a promising stimulation strategy that may further increase spectral resolution and frequency selectivity with CIs. PMID- 27562805 TI - Financial burden and quality of life of informal caregivers of patients with wet age-related macular degeneration. AB - PURPOSE: The purpose of this research is to quantify the cost burden, care times and the impact on the quality of life (QoL) of informal caring relatives caring for patients with wet age-related macular degeneration (wet AMD). Moreover we investigated the impact of care times on the QoL. METHODS: Through a specifically designed questionnaire, 150 caring relatives were interviewed retrospectively on all accrued financial costs, caring times incurred and the current QoL, assessed by a Visual Analogue Scale for happiness (VAS). RESULTS: The caring time incurred was on average 6.4 +/- 8.5 (mean +/- SD) hours per week. The QoL was on average rated at 6.7 +/- 1.9 on a ten point scale. Financial strain was incurred by the direct non-medical costs of on average ? 405 +/- 1104 and the direct medical costs of on average ? 134 +/- 340 per year. Indirect costs were stated by two caregivers as amounting to ? 2400 and ? 6000 net income loss per year respectively. Caregivers of privately insured patients with wet AMD carried a financial cost burden which was up to six times higher than caregivers of patients who were on state insurance while showing the same visual acuity. CONCLUSION: The evaluation shows that caregivers of privately insured patients with wet AMD have higher costs than caregivers of patients with state insurance coverage. This burden seems to be a factor to be considered independently since it does not appear to have any relation to patients AMD acuity. PMID- 27562806 TI - Micro/Nanospheres Generation by Fluid-Fluid Interaction Technology: A Literature Review. AB - This review focuses on the fundamental fluid mechanics which governs the generation of micro/nanospheres. The micro/nanosphere generation process has gathered significant attention in the past two decades, since micro/nanospheres are widely used in drug delivery, food science, cosmetics, and other application areas. Many methods have been developed based on different operating principles, such as microfluidic methods, electrospray methods, chemical methods, and so forth. This paper focuses on microfluidic methods. Although the structure of the microfluidic devices may be different, the operating principles behind them are often very similar. Following an initial discussion of the fluid mechanics related to the generation of microspheres, various design approaches are discussed, including T-junction, flow focusing, membrane emulsification, modified T-junction, and double emulsification methods. The advantages and problems associated with each method are also discussed. Next, the most commonly used computational fluid dynamics (CFD) methods are reviewed at three different levels: microscopic, mesoscopic, and macroscopic. Finally, the issues identified in the current literature are discussed, and some suggestions are offered regarding the future direction of technology development related to micro/nanosphere generation. Few relevant patents to the topic have been reviewed and cited. PMID- 27562807 TI - Orthopaedic disorders of pycnodysostosis: a report of five clinical cases. AB - PURPOSE: Pycnodysostosis is a rare autosomal recessive genetic disorder usually diagnosed at an early age. The few previously published case series have generally focused on maxillofacial manifestations and genetic considerations. The purpose of this study was to evaluate the clinical characteristics and differential diagnosis of pycnodysostosis focusing on its orthopaedic manifestations, which have been poorly described in the literature. METHODS: We evaluated clinical and radiographic characteristics of five patients with pycnodysostosis. RESULTS: Three male and two female patients were included in the study. One patient had consanguineous parents and two had a family history of pycnodysostosis. One patient was of normal height; four with short stature underwent growth hormone treatment. Most patients had bone fractures. All had typical cranial and orofacial manifestations, partial dysplasia of the terminal phalanges and increased bone density. Aplastic acromial ends and spondylolysis were not seen in any patient. Some patients had genu valgus, ankle valgus or sleep apnea; two required tympanic drains for serous otitis media. Two patients experienced nonunion. CONCLUSIONS: Short stature is a consistent feature of pycnodysostosis that can be treated with growth hormone. To our knowledge, serous otitis media, nonunion and other orthopaedic manifestations have not been previously described in pycnodysostosis patients. Intramedullary nailing osteosynthesis can be difficult in these patients because of skeletal sclerosis; therefore, other surgical options should be considered. Nonunion is common in this population. Pycnodysostosis is a poorly described disease, but clinicians should be aware of its potential manifestations in order to appropriately diagnose, manage and follow-up patients. PMID- 27562808 TI - Toxicity and oxidative stress induced by chromium in workers exposed from different occupational settings around the globe: A review. AB - The present review focused on the levels and toxicological status of heavy metals especially chromium (Cr) in the exposed workers from different occupational settings around the globe and in Pakistan. It was found that exposed workers from leather tanning and metal plating units showed elevated levels of Cr than the workers from other occupational settings. Cr and other heavy metals level in biological matrices of the exposed workers in different occupational settings revealed that developing countries are severely contaminated. Occupational settings from the Sialkot district, Pakistan exhibited elevated level of Cr in biological entities of the exposed workers. Review suggested that higher level of Cr exposure to the workers enhance the oxidative stress (reactive oxygen species (ROS) and hydroxyl (OH) radical generation) which may cause; cellular and molecular damage such as genotoxicity and chromosomal aberration formations, and carcinogenic effects. This review will help to understand the Cr contamination mechanisms and associated health implications in different occupational settings around the globe in general and particularly to Pakistan. This study will also assist occupational health and safety management authorities to devise or change the Cr recommended exposure limits (REL) for different occupational settings. PMID- 27562809 TI - Heterogeneous UV/Fenton degradation of bisphenol A catalyzed by synergistic effects of FeCo2O4/TiO2/GO. AB - A new method for bisphenol A (BPA) degradation in aqueous solution was developed. The characteristics of BPA degradation in a heterogeneous ultraviolet (UV)/Fenton reaction catalyzed by FeCo2O4/TiO2/graphite oxide (GO) were studied. The properties of the synthesized catalysts were characterized using scanning electron microscopy, X-ray diffraction, and vibrating sample magnetometry. FeCo2O4 and TiO2 were grown as spherical shape, rough surface, and relatively uniform on the surface of GO (FeCo2O4/TiO2/GO). Batch tests were conducted to evaluate the effects of the initial pH, FeCo2O4/TiO2/GO dosage, and H2O2 concentration on BPA degradation. In a system with 0.5 g L-1 of FeCo2O4/TiO2/GO and 10 mmol L-1 of H2O2, approximately 90 % of BPA (20 mg L-1) was degraded within 240 min of UV irradiation at pH 6.0. The reused FeCo2O4/TiO2/GO catalyst retained its activity after three cycles, which indicates that it is stable and reusable. The heterogeneous UV/Fenton reaction catalyzed by FeCo2O4/TiO2/GO is a promising advanced oxidation technology for treating wastewater that contains BPA. PMID- 27562810 TI - Influence of the presence of ruthenium on the activity and stability of Co-Mg-Al based catalysts in CO2 reforming of methane for syngas production. AB - Hydrogen production by methane dry reforming is an important yet challenging process. A performing catalyst will favor the thermodynamic equilibrium while ensuring good hydrogen selectivity. We hereby report the synthesis of Co x Mg6-x Al2 (with x = 2 and 6) mixed oxide catalysts synthesized via hydrotalcite precursors and the synthesis of a ruthenium-based catalyst on a cobalt, magnesium, and aluminum mixed oxide supports Ru/Co x Mg6-x Al2 (with x = 2 and 6). The impregnation of ruthenium on the hydrotalcites was performed in two ways: by impregnation on the dried hydrotalcite and by memory effect on hydrotalcite calcined at 500 degrees C. The deposition of ruthenium by memory effect of the magnesium and cobalt support allows the generation of both metallic and basic sites which provides an active and stable catalyst for the dry reforming reaction of methane. PMID- 27562812 TI - Electrolytic removal of alizarin red S by Fe/Al composite hydrogel electrode for electrocoagulation toward a new wastewater treatment. AB - This paper studies Fe/Al composite hydrogel electrode electrocoagulation (EC) and adsorption of alizarin red S (ARS). ARS removal efficiency and degradation mechanism when applying Fe/Al composite hydrogel electrode were investigated. The optimum experimental factors and degradation of ARS were discussed. ARS degradation was optimal operation at initial pH 3 with O2.The experimental results showed that the COD removal efficiency was better, reaching to about 90 % when applying the novel electrode system. The discoloration rate also reached the best effect of 99 % in the superior technical conditions. The optimum electrolysis time is about 30 min. Results revealed that the efficiency in the EC process with Fe/Al composite hydrogel electrodes were much better than that in conventional electrode system. In addition, Fe/Al composite hydrogel electrodes are environment-friendly material, which reuse waste and reduce cost. Hydrogel has certain iron exchange capacity to eliminate the residual metal irons. It is found that the application of ultrasonic helps to accelerate the electrocoagulation of ARS. This study not only realizes the ultrasonic, flotation, coagulation, and adsorption of the combination but also gains economy and environment. Consequently, the unique performance of Fe/Al composite hydrogel electrodes opens promising perspectives for fast, high, and economical treatment of wastewater containing dyes or/and organic contaminants. PMID- 27562811 TI - Enhanced excess sludge hydrolysis and acidification in an activated sludge side stream reactor process with single-stage sludge alkaline treatment: a pilot scale study. AB - A pilot-scale side-stream reactor process with single-stage sludge alkaline treatment was employed to systematically investigate characteristics of excess sludge hydrolysis and acidification with alkaline treatment and evaluate feasibility of recovering a carbon source (C-source) from excess sludge to enhance nutrient removal at ambient temperature. The resulting C-source and volatile fatty acid specific yields reached 349.19 mg chemical oxygen demand (COD)/g volatile suspended solids (VSS) d-1 and 121.3 mg COD/g VSS d-1, respectively, the process had excellent C-source recovery potential. The propionic-to-acetic acid ratio of the recovered C-source was 3.0 times that in the influent, which beneficially enhanced biological phosphorus removal. Large populations and varieties of hydrolytic acid producing bacteria cooperated with alkaline treatment to accelerate sludge hydrolysis and acidification. Physicochemical characteristics indicated that recovered C-source was derived primarily from extracellular polymeric substances hydrolysis rather than from cells disruption during alkaline treatment. This study showed that excess sludge as carbon source was successfully recycled by alkaline treatment in the process. PMID- 27562813 TI - Dual mechanochemical immobilization of heavy metals and decomposition of halogenated compounds in automobile shredder residue using a nano-sized metallic calcium reagent. AB - Simultaneous immobilization of heavy metals and decomposition of halogenated organic compounds in different fractions of automobile shredder residue (ASR) were achieved with a nano-sized metallic calcium through a 60-min ball milling treatment. Heavy metal (HM) immobilization and chlorinated/brominated compound (CBC) decomposition efficiencies both reached 90-100 %, after ball milling with nanometallic calcium/calcium oxide (Ca/CaO) dispersion, regardless of ASR particle size (1.0, 0.45-1.0, and 0.250 mm). Concentrations of leachable HMs substantially decreased to a level lower than the regulatory standard limits (Co and Cd 0.3 mg L-1; Cr 1.5 mg L-1; Fe, Pb, and Zn 3.0 mg L-1; Mn and Ni 1 mg L-1) proposed by the Korean hazardous waste elution standard regulatory threshold. Scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS) element maps/spectra showed that while the amounts of HMs and CBCs detectable in ASR significantly decreased, the calcium mass percentage increased. X-ray powder diffraction (XRD) patterns indicate that the main fraction of enclosed/bound materials on ASR includes Ca-associated crystalline complexes that remarkably inhibit HM desorption and simultaneously transform dangerous CBCs into harmless compounds. The use of a nanometallic Ca/CaO mixture in a mechanochemical process to treat hazardous ASR (dry conditions) is an innovative approach to remediate cross-contaminated residues with heavy metals and halogenated compounds. PMID- 27562814 TI - Government employees' perception of urban air pollution and willingness to pay for improved quality: a cross-sectional survey study in Nanchang, China. AB - To improve the public's awareness of urban air pollution and promote establishment of more efficient policy toward urban air pollution, we investigated the government employees' perceptions of current urban air pollution and their willingness to pay (WTP) taxes for improved quality in Nanchang, China. Stratified cluster sampling strategy was used to distribute 629 questionnaires, and 608 were completed anonymously, yielding a 96.7 % response rate. Descriptive statistics frequencies and proportions were used to summarize the sample characteristics, and logistic regression models were performed to assess the associations of perception of urban air quality and WTP versus demographic variables. We found low awareness of urban air pollution (34.5 %) as well as low WTP (44.9 %), especially among the middle aged people (age 30-39 and age 40-49). Our study shows that female employees have better awareness of urban air pollution but much less willingness to pay for air quality improvement. Majority of the government employees showed their support to the government for more effective policies toward environmental protection, indicating more enhanced public education and environmental protection campaigns to improve the public's awareness of air pollution and work with every citizen to improve air quality. This study also obtained baseline information useful to the local regional and even national government in developing nations in their attempt to control urban air pollution in future. PMID- 27562815 TI - Ovarian sex steroid receptors and sex hormones in androgenized rats. AB - This study evaluated for the first time the effects of different doses of the anabolic steroid nandrolone decanoate (ND) on the expression of ovarian steroid receptors (AR, ER-alpha (ESR1) and ER-beta (ESR2)) and related sex hormones after treatment and recovery periods in adult rats. The animals were injected subcutaneously with doses of ND (1.87, 3.75, 7.5 or 15 mg/kg b.w.) or mineral oil (control group) for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment and recovery for a period of 30 days and (c) ND treatment and recovery for a period of 60 days. Estrous cycle was monitored daily. At the end of each period, rats were killed for collection of blood and ovaries. Persistent diestrus occurred in all rats during ND treatment and after 30-day recovery. The highest dose of ND was able to maintain all rats arrested at diestrus until 60-day recovery. The expression of steroid receptors varied in a dose- and period-dependent manner, having a more pronounced response with the dose of 15 mg ND/kg. ND treatment increased serum levels of testosterone, 17beta-estradiol and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg. No change was observed in the levels of follicle-stimulating hormone (FSH), whereas levels of the luteinizing hormone (LH) varied according to the dose and period. In conclusion, the ovarian sex steroid receptors and sex hormones were restored only at lower doses of ND and after a longer period of recovery. PMID- 27562816 TI - Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP). AB - BACKGROUND/AIMS: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. METHODS: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. RESULTS: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26MUM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3beta signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. CONCLUSIONS: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer. PMID- 27562817 TI - Protective role of heme oxygenase-1 in atrial remodeling. AB - Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 cell line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-beta (TGF-beta) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-beta enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up regulation of collagen by TGF-beta, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1(-/-) mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1(-/-) mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development. PMID- 27562818 TI - CuO Nanoparticles Inhibited Root Growth from Brassica nigra Seedlings but Induced Root from Stem and Leaf Explants. AB - Interests associated with nanoparticles (NPs) are budding due to their toxicity to living species. The lethal effect of NPs depends on their nature, size, shape, and concentration. Present investigation reports that CuO NPs badly affected Brassica nigra seed germination and seedling growth parameters. However, variation in antioxidative activities and nonenzymatic oxidants is observed in plantlets. Culturing the leaf and stem explants on MS medium in presence of low concentration of CuO NPs (1-20 mg l-1) produces white thin roots with thick root hairs. These roots also show an increase in DPPH radical scavenging activity (up to 80 % at 10 mg l-1), total antioxidant, and reducing power potential (maximum in presence of 10 mg l-1 CuO NPs in the media). Nonenzymatic antioxidative molecules, phenolics and flavonoids, are observed elevated but NPs concentration dependent. We can conclude that CuO NPs can induce rooting from plant explants cultured on appropriate medium. These roots can be explored for the production of active chemical constituents. PMID- 27562819 TI - Gastric microbiota and carcinogenesis - Current evidence and controversy. AB - Growing research on the human microbiome, even beyond the gastrointestinal area, is not surprising mainly due to significant advances in study methods. Current reporting in this area is so intensive that clinicians are changing the unsuitable "bacterial flora" expression for more appropriate terms such as "microbiota" (the entire microbial community colonizing an ecologic niche), "microbiome" (their collective genome), or "dysbiosis" (microbial composition imbalance with respect to the normatively considered pattern). Since the diseases involved in the altered microbiota hypothesis are increasing, its implication for cancer should come as no surprise to us. PMID- 27562820 TI - Shape-selective Valorization of Biomass-derived Glycolaldehyde using Tin containing Zeolites. AB - A highly selective self-condensation of glycolaldehyde to different C4 molecules has been achieved using Lewis acidic stannosilicate catalysts in water at moderate temperatures (40-100 degrees C). The medium-sized zeolite pores (10 membered ring framework) in Sn-MFI facilitate the formation of tetrose sugars while hindering consecutive aldol reactions leading to hexose sugars. High yields of tetrose sugars (74 %) with minor amounts of vinyl glycolic acid (VGA), an alpha-hydroxyacid, are obtained using Sn-MFI with selectivities towards C4 products reaching 97 %. Tin catalysts having large pores or no pore structure (Sn Beta, Sn-MCM-41, Sn-SBA-15, tin chloride) led to lower selectivities for C4 sugars due to formation of hexose sugars. In the case of Sn-Beta, VGA is the main product (30 %), illustrating differences in selectivity of the Sn sites in the different frameworks. Under optimized conditions, GA can undergo further conversion, leading to yields of up to 44 % of VGA using Sn-MFI in water. The use of Sn-MFI offers multiple possibilities for valorization of biomass-derived GA in water under mild conditions selectively producing C4 molecules. PMID- 27562821 TI - Optic disc optical coherence tomography imaging through a black intraocular lens. PMID- 27562822 TI - Internal dressings for healing perianal abscess cavities. AB - BACKGROUND: A perianal abscess is a collection of pus under the skin, around the anus. It usually occurs due to an infection of an anal gland. In the UK, the annual incidence is 40 per 100,000 of the adult population, and the standard treatment is admission to hospital for incision and drainage under general anaesthetic. Following drainage of the pus, an internal dressing (pack) is placed into the cavity to stop bleeding. Common practice is for community nursing teams to change the pack regularly until the cavity heals. Some practitioners in the USA and Australia make a small stab incision under local anaesthetic and place a catheter into the cavity which drains into an external dressing. It is removed when it stops draining. Elsewhere in the USA, simple drainage is performed in an outpatient setting under local anaesthetic. OBJECTIVES: To assess the effects of internal dressings in healing wound cavities resulting from drainage of perianal abscesses. SEARCH METHODS: In May 2016 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL Plus. We also searched clinical trial registries to identify ongoing and unpublished studies, and searched reference lists of relevant reports to identify additional studies. We did not restrict studies with respect to language, date of publication, or study setting. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) comparing any type of internal dressing (packing) used in the post operative management of perianal abscess cavities with alternative treatments or different types of internal dressing. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment, and data extraction. MAIN RESULTS: We included two studies, with a total of 64 randomised participants (50 and 14 participants) aged 18 years or over, with a perianal abscess. In both studies, participants were enrolled on the first post operative day and randomised to continued packing by community district nursing teams or to no packing. Participants in the non-packing group managed their own wounds in the community and used absorbant dressings to cover the area. Fortnightly follow-up was undertaken until the cavity closed and the skin re epithelialised, which constituted healing. For non-attenders, telephone follow-up was conducted.Both studies were at high risk of bias due to risk of attrition, performance and detection bias.It was not possible to pool the two studies for the outcome of time to healing. It is unclear whether continued post-operative packing of the cavity of perianal abscesses affects time to complete healing. One study reported a mean time to wound healing of 26.8 days (95% confidence interval (CI) 22.7 to 30.7) in the packing group and 19.5 days (95% CI 13.6 to 25.4) in the non-packing group (it was not clear if all participants healed). We re analysed the data and found no clear difference in the time to healing (7.30 days longer in the packing group, 95% CI -2.24 to 16.84; 14 participants). This was assessed as very low quality evidence (downgraded three levels for very serious imprecision and serious risk of bias). The second study reported a median time to complete wound healing of 24.5 days (range 10 to 150 days) in the packing group and 21 days (range 8 to 90 days) in the non-packed group. There was insufficient information to be able to recreate the analysis and the original analysis was inappropriate (did not account for censoring). This second study also provided very low quality evidence (downgraded four levels for serious risk of bias, serious indirectness and very serious imprecision).There was very low quality evidence (downgraded for risk of bias, indirectness and imprecision) of no difference in wound pain scores at the initial dressing change. Both studies also reported patients' retrospective judgement of wound pain over the preceding two weeks (visual analogue scale, VAS) as lower for the non-packed group (2; both studies) compared with the packed group (0; both studies); (very low quality evidence) but we have been unable to reproduce these analyses as no variance data were published.There was no clear evidence of a difference in the number of post operative fistulae detected between the packed and non-packed groups (risk ratio (RR) 2.31, 95% CIs 0.56 to 9.45, I(2) = 0%) (very low quality evidence downgraded three levels for very serious imprecision and serious risk of bias).There was no clear evidence of a difference in the number of abscess recurrences between the packed and non-packed groups over the variable follow-up periods (RR 0.72, 95% CI 0.22 to 2.37, I(2) = 0%) (very low quality evidence downgraded three levels for serious risk of bias and very serious imprecision).No study reported participant health-related quality of life/health status, incontinence rates, time to return to work or normal function, resource use in terms of number of dressing changes or visits to a nurse, or change in wound size. AUTHORS' CONCLUSIONS: It is unclear whether using internal dressings (packing) for the healing of perianal abscess cavities influences time to healing, wound pain, development of fistulae, abscess recurrence or other outcomes. Despite this absence of evidence, the practice of packing abscess cavities is commonplace. Given the lack of high quality evidence, decisions to pack may be based on local practices or patient preferences. Further clinical research is needed to assess the effects and patient experience of packing. PMID- 27562823 TI - The role of emotion regulation in the experience of menstrual symptoms and perceived control over anxiety-related events across the menstrual cycle. AB - Hormonal variation throughout the menstrual cycle is posited to impact various physical and mental health symptoms; however, this is not observed in all women and mechanisms are not well understood. Difficulty in emotion regulation may elucidate differences that women experience in physical and mental health functioning between menstrual phases. We examined the moderating role of difficulty in emotion regulation in the relation between menstrual phase and menstrual symptom severity and perceived control over anxiety-related events, in healthy, regularly menstruating women. The participants were 37 women (Mage = 26.5, SD = 9.6). A series of regression analyses were used to examine whether individual differences in emotion regulation difficulties moderate the relation between menstrual phase and our outcomes, severity of menstrual symptoms and perceived control over anxiety-related events, using a within-subjects design. The analyses revealed that difficulty in emotion regulation significantly moderated the relation between menstrual phase and perceived control over anxiety related events (beta = -0.42, p < .05), but not menstrual symptom severity. Women who reported higher emotion regulation difficulty experienced greater differences in perceived control over anxiety-related events between menstrual phases. Specifically, women with lower difficulty in emotion regulation report greater increase in control over anxiety during the late luteal phase compared to women with higher emotion regulation difficulty. Difficulty in emotion regulation may play an important role in understanding differences in menstrual phase-associated impairments, thereby informing the development of targeted interventions for vulnerable women. PMID- 27562824 TI - Are participants in face-to-face and internet support groups the same? Comparison of demographics and depression levels among women bereaved by stillbirth. AB - Support groups can help individuals cope with difficult health situations but have been understudied for women with perinatal bereavement. An early study suggested those using internet support groups had high rates of positive depression screens, raising the question whether these users were more symptomatic than those in similar face-to-face support groups. We therefore conducted two convenience sample surveys of women bereaved by perinatal loss, one looking at use of online support groups and the other in-person support groups. The surveys identified demographics, use of peer support, potential confounders, and current depression symptoms using the Edinburgh Postnatal Depression Scale (EPDS). Four hundred sixteen women from 18 internet groups and 60 women from 13 in-person groups met inclusion criteria. Participants in both groups were predominantly Caucasian, highly educated, and had private insurance. Severe depression symptoms were similar in the two groups despite the different modalities. Women in both face-to-face or internet groups for pregnancy and perinatal loss demonstrated similar scores on depression screens. Women of color, poor, and less-educated women were starkly underrepresented in both types of groups, raising questions about knowledge of support options, barriers to use, preferences for bereavement support, and optimization of groups for a broader population. PMID- 27562826 TI - Risky substance use among young adults in the nightlife arena: An underused setting for risk-reducing interventions? AB - AIMS: Alcohol and illicit substance use among young adults carries the risk of adverse consequences like violence, injuries, risky sexual behaviour and, ultimately, the development of possible addiction. The nightlife arena is a high risk setting for excessive substance use and the aims of this study were to examine prevalence rates and identify high-risk subgroups in this context. METHODS: Patrons ( n = 1099, response rate 76%) entering or exiting 12 popular licensed premises in downtown Oslo, Norway, completed an anonymous self administered questionnaire and their blood alcohol concentration (BAC) levels were measured using a Breathalyzer. RESULTS: The average BAC levels were similar ( t = 1.67, degrees of freedom (df)= 936, non-significant (ns)) and high both for males (1.030/00) and females (0.970/00). A total of 67% reported ever using illicit drugs, 43% reported last-year use, 25% last-month use and 14% use during the last 48 hours. High-risk groups included the youngest patrons (16-20 years) where 50% reported illicit drug use in the last year. Males reported more use of illicit drugs than females, whereas females had equally high alcohol consumption frequency and intoxication levels as males. Young age, male gender, frequent alcohol intoxications and age < 15 for first alcohol intoxication experience were associated with increased risk of illegal substance use in multivariate analyses. CONCLUSIONS: The high levels of alcohol and illicit drug use, particularly among patrons younger than 21 years, should be of concern to the community, policymakers and the nightlife industry. The nightlife arena may be an under utilized setting for the implementation of risk-reducing interventions. PMID- 27562827 TI - Fathers' depressive symptoms in the postnatal period: Prevalence and correlates in a population-based Swedish study. AB - AIMS: The aim of this study was to investigate the prevalence and correlates of depression in new fathers. METHODS: A population-based sample of 885 Swedish fathers and their partners completed a questionnaire, including the Edinburgh Postnatal Depression Scale at three months postpartum. Correlates of depressive symptoms were analysed with univariate and multiple variable regression models. RESULTS: Symptoms of depression were found in 6.3% of the fathers and 12.0% of the mothers, and the point prevalence of major depression in fathers was 1.3%. The strongest correlates of depressive symptoms in fathers were problems in the partner relationship, a low educational level, previous depression, stressful life events and low partner support. The cross-sectional design could affect the magnitude of the results, and causal inferences cannot be made. CONCLUSIONS: Although the rate of depressive symptoms is lower in fathers than in mothers at three months postpartum, the associated factors are similar to those found in studies of mothers. The first visits at the child health centre could include a discussion with both parents about normal transition problems; balancing work, personal and family needs; and distress. When signs of distress or partner relationship difficulties are picked up, this should be followed up and support interventions offered. PMID- 27562825 TI - Androgens induce a distinct response of epithelial-mesenchymal transition factors in human prostate cancer cells. AB - Inhibition of the androgen receptor (AR) is a major target of prostate cancer (PCa) therapy. However, prolonged androgen deprivation results eventually in castration-resistant PCa (CRPC) with metastasis and poor survival. Emerging evidence suggests that epithelial-mesenchymal transition (EMT) may facilitate castration-resistance and cancer metastasis in PCa. The human androgen-dependent, castration-sensitive prostate cancer (CSPC) cell line LNCaP and the CRPC cell line C4-2 are often used as a model system for human PCa. However, the role of the AR and the effect of AR antagonist (antiandrogen) treatment on the RNA expression of key factors of EMT including the long non-coding RNAs (lncRNAs) DRAIC in PCa cells remain elusive. Although as expected the established AR target genes PSA and FKBP5 are strongly induced by androgens in both cell lines, both E cadherin and vimentin mRNA levels are upregulated by androgens in LNCaP but not in C4-2 cells by short- and long-term treatments. The mRNA levels of E-cadherin and vimentin remain unchanged by antiandrogen treatment in both cell lines. The expression of transcription factors that regulate EMT including Slug, Snail and ZEB1 and the lncRNA DRAIC were affected by androgen treatment in both cell lines. The mRNA level of Slug is upregulated by androgens and interestingly downregulated by antiandrogens in both cell lines. On the other hand, ZEB1 mRNA levels are strongly upregulated by androgens but remain unchanged by antiandrogens. In contrast, Snail mRNA levels are repressed by androgen treatment similar to DRAIC RNA levels. However, while antiandrogen treatment seems not to change Snail mRNA levels, antiandrogen treatments induce DRAIC RNA levels. Moreover, despite the strong upregulation of Zeb1 mRNA, no significant increase of the ZEB1 protein was observed indicating that despite androgen upregulation, posttranscriptional regulation of EMT controlling transcription factors occurs. SLUG protein was enhanced in both cell lines by androgens and reduced by antiandrogens. Taken together, our data suggest that the ligand-activated AR regulates the expression of several EMT key factors and antiandrogens counteract AR activity only on selected genes. PMID- 27562828 TI - The similarity and difference between ant and human ultrasocieties: From the viewpoint of scaling laws. AB - Complementary to Gowdy & Krall's comparison between ants and humans, I use economy scaling laws to discuss the similarity and difference between them quantitatively. I hypothesize that individual variations in society result in higher energetic efficiency in larger groups, and that the difference in the sustainability between these species originates from the driving forces of growth with different scaling powers. PMID- 27562829 TI - Type A ganglion cysts of the radiocapitellar joint may involve compression of the superficial radial nerve. AB - INTRODUCTION: Two types of ganglion cysts at the elbow have been described depending on their anatomic location. Type A ganglion cyst is located proximal to the arcade of Frohse, and type B distal to it. Compressive neuropathies of the radial nerve at the level of the radial tunnel may lead to two different clinical entities with different clinical manifestations. These different conditions depend on which branch is involved. Although compression of the deep motor branch due to a ganglion cyst has been previously described, affection of the superficial sensory branch is considered much rarer. The aim of this study was to describe a series of patients in which painful and dysesthetic symptoms arose from superficial radial nerve compression due to type A ganglion cysts coming from the radiocapitellar joint. METHODS: A review of currently available literature about the disease was carried out. The clinical, histological and radiological records of a series of eight cases (seven patients) with compression of the superficial radial nerve diagnosed and treated between 2008 and 2011 were retrospectively reviewed. All patients complained of pain and dysesthesia at the lateral aspect of the elbow. All patients were initially diagnosed and managed as lateral epicondylitis. Persistence of the symptoms was evidenced in all patients after a course of six months of non-operative management. Magnetic resonance imaging was performed and revealed the presence of a mass compatible with a ganglion cyst coming from the radiocapitellar joint, pushing up the superficial sensory branch of the radial nerve and compressing it against the extensor carpi radialis brevis. Surgical excision was performed in all cases. RESULTS: Histology confirmed the diagnosis of ganglion cysts. Histological findings consisted of dense fibrous tissue, with no synovial or epithelial lining and mucoid material with foamy macrophages. The mean follow-up after surgical excision was 28months (range 24-30). The symptoms subsided in all cases. No complications were registered during the follow-up. CONCLUSION: Type A ganglion cysts of the radiocapitellar joint may involve compression of the superficial radial nerve. Our series of eight cases may suggest that this pathology might not be as rare as it was thought before. This evidence may be useful for the orthopaedic population, who may have another differential diagnosis when managing cases of painful symptoms located in the lateral aspect of the elbow. TYPE OF STUDY: Therapeutic study. LEVEL OF EVIDENCE: IV. PMID- 27562830 TI - Locally induced laminar convection in liquid nitrogen and silicone oils. AB - We present an experimental study of a laminar convective phenomenon induced by a centimetric heater totally immersed in a liquid pool (Rayleigh number ranging from 10(4) to 10(7)). This local heating is observed to induce a laminar convection that differs from the classical Rayleigh-Benard cells created by heating the whole bottom of the fluid: the convection pattern is no more periodic. In order to obtain a complete map of the velocity field, we use Particle Image Velocimetry technique. The vertical velocity between the counter rotating convective cells is used as the relevant physical parameter to describe the phenomenon. The potential cooling applications of this problem lead us to choose liquid nitrogen as an experimental fluid. We thus compare the results obtained for various temperature gradients in liquid nitrogen with experiments performed at room temperature with silicone oils of various viscosities. The theoretical law for the maximal vertical velocity from classical Rayleigh-Benard experiments is adapted to the specific geometry investigated by using a new definition for the characteristic wavelength. This length is studied and appears to be dependent on the liquid properties. We finally obtain a remarkable agreement between theory and experimental data. PMID- 27562831 TI - Active Brownian motion of emulsion droplets: Coarsening dynamics at the interface and rotational diffusion. AB - A micron-sized droplet of bromine water immersed in a surfactant-laden oil phase can swim (S. Thutupalli, R. Seemann, S. Herminghaus, New J. Phys. 13 073021 (2011). The bromine reacts with the surfactant at the droplet interface and generates a surfactant mixture. It can spontaneously phase-separate due to solutocapillary Marangoni flow, which propels the droplet. We model the system by a diffusion-advection-reaction equation for the mixture order parameter at the interface including thermal noise and couple it to fluid flow. Going beyond previous work, we illustrate the coarsening dynamics of the surfactant mixture towards phase separation in the axisymmetric swimming state. Coarsening proceeds in two steps: an initially slow growth of domain size followed by a nearly ballistic regime. On larger time scales thermal fluctuations in the local surfactant composition initiates random changes in the swimming direction and the droplet performs a persistent random walk, as observed in experiments. Numerical solutions show that the rotational correlation time scales with the square of the inverse noise strength. We confirm this scaling by a perturbation theory for the fluctuations in the mixture order parameter and thereby identify the active emulsion droplet as an active Brownian particle. PMID- 27562832 TI - On the interaction of dipolar filaments. AB - The interactions of dipolar filaments such as magnetic needles and chains in strong homogeneous magnetic/electric field are investigated theoretically. Revisiting the case of uniformly magnetized/polarized parallel needles of finite size L and separated by a distance R , all the relevant regimes of attraction and/or repulsion are properly addressed and discussed. At short inter-needle separation ( R/L ? 0.2, the repuive pair potential of two facing needles is governed by R(-1) in strong contrast with R(-3) at long separations (R/L ? 2.5). This softening is attributed to an efficient long-range screening owing to the relatively long needle extension in this regime. This whole understanding of dipolar needles effective interaction is then used to grasp that of dipolar chains made up of spherical dipolar beads. When excluded-volume correlations are weak (i.e., the chains are a few beads apart), chains and needles possess virtually the same effective interaction. However, at short separation there is a remarkable hardening upon approaching two chains in registry in qualitative contrast to the needles case. PMID- 27562833 TI - Consequences of the Now-or-Never bottleneck for signed versus spoken languages. AB - Signed and spoken languages emerge, change, are acquired, and are processed under distinct perceptual, motor, and memory constraints. Therefore, the Now-or-Never bottleneck has different ramifications for these languages, which are highlighted in this commentary. The extent to which typological differences in linguistic structure can be traced to processing differences provides unique evidence for the claim that structure is processing. PMID- 27562834 TI - Fat Grafting with Tissue Liquefaction Technology as an Adjunct to Breast Reconstruction. AB - BACKGROUND: Tissue liquefaction technology (TLT) delivers warmed saline from the liposuction cannula tip at low pressure pulses to disaggregate adipocytes. This technology differs significantly from that used in other liposuction devices including water jet-assisted liposuction. Here we introduce our early experience with this technology in the setting of fat transfer for revision breast reconstruction. METHODS: A retrospective chart review of 136 consecutive patients who underwent fat harvest with TLT and subsequent transfer into 237 breast reconstructions was conducted at a single institution. This two-surgeon series examined donor and recipient site complication rates over a median follow-up of 143 days [87-233]. RESULTS: The overall complication rate was 28.7 %, of which the majority (22.1 %) was fat necrosis at the recipient site as documented by any clinical, imaging, or pathologic evidence. The abdomen served as the donor site for half of the cases. Donor site complications were limited to widespread ecchymosis of the donor site notable in 10.4 % of cases. Twenty-five percent of patients had received postmastectomy radiotherapy prior to fat transfer. Prior to revision with fat transfer, implant-based breast reconstruction was used in 75.5 % of cases, and autologous flaps in the remainder. Fat transfer was combined with other reconstructive procedures 94.1 % of the time. CONCLUSIONS: TLT can be used to harvest adipocytes for fat transfer with donor site morbidity and recipient site complications comparable to other modalities. The efficiency and quality of harvested fat makes this technology appealing for wide spread adoption during fat transfer. LEVEL OF EVIDENCE IV: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27562836 TI - Erratum to: Comparative Analysis of Length of Stay and Inpatient Costs for Orthopedic Surgery Patients Treated with IV Acetaminophen and IV Opioids vs. IV Opioids Alone for Post-Operative Pain. PMID- 27562835 TI - Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy. AB - : Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective alpha2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects. FUNDING: Galderma International S.A.S., Paris, France. PMID- 27562837 TI - Natural history and life-threatening complications in Myhre syndrome and review of the literature. AB - Myhre syndrome (OMIM 139210) is a rare developmental disorder inherited as an autosomal dominant trait and caused by a narrow spectrum of missense mutations in the SMAD4 gene. The condition features characteristic face, short stature, skeletal anomalies, muscle pseudohypertrophy, restricted joint mobility, stiff and thick skin, and variable intellectual disability. While most of the clinical features manifest during childhood, the diagnosis may be challenging during the first years of life. We report on the evolution of the clinical features of Myhre syndrome during childhood in a subject with molecularly confirmed diagnosis. The clinical records of 48 affected patients were retrospectively analysed to identify any early clinical signs characterizing this disorder and to better delineate its natural history. We also note that pericarditis and laryngotracheal involvement represent important life-threatening complications of Myhre syndrome that justify the recommendation for cardiological and ENT follow-up for these patients. CONCLUSION: Short length/stature, short palpebral fissures, and brachydactyly with hyperconvex nails represent signs/features that might lead to the correct diagnosis in the first years of life and direct to the proper molecular analysis. We underline the clinical relevance of pericarditis and laryngotracheal stenosis as life-threatening complications of this disorder and the need for careful monitoring, in relation to their severity. WHAT IS KNOWN: * The clinical and radiological signs of the disease in children older than 7-8 years. * Pericarditis, sometimes occurring with constrictive pericardium requiring pericardiectomy, has been reported as a recurrent feature but has not been adequately stressed in previous literature. What is New: * Short length/stature, short palpebral fissures, brachydactyly with hyperconvex nails represent clinical signs that might lead to diagnosis in the first years of life. * Review of the literature showed that pericarditis and laryngotracheal complications represent major recurrent issues in patients with Myhre syndrome. PMID- 27562838 TI - The effect of kangaroo ward care in comparison with "intermediate intensive care" on the growth velocity in preterm infant with birth weight <1100 g: randomized control trial. AB - Kangaroo mother care (KMC) reduces neonatal mortality, neonatal sepsis and improves growth outcome in preterm infants. In this study, we compared the efficacy of "baby care in kangaroo ward (KWC)" with "baby care in intermediate intensive care (IIC)" in stable preterm infants (birth weight <1100 g) for improving the growth velocity till term corrected age. One hundred and forty-one infants were randomized to KWC (n = 71) or IIC (n = 70) once the infant reached a weight of 1150 g. Infants in the KWC group were shifted to the KWC immediately after randomization and those in the IIC group were given care in the IIC till they attained a weight of 1250 g and then shifted to the KWC. The average weight gains as well as weight, length, and head circumference at term corrected age were comparable in both the groups. There was significant reduction in IIC stay post randomization and increase in weight gain before discharge in the KWC group. There was a significant increase in incidence of apnea in the IIC group. CONCLUSION: Early KWC is equally efficacious as IIC in improving the growth outcomes of stable preterm (birth weight <1100 g) infants at term gestational age. CLINICAL TRIAL REGISTRATION: Clinical trial registry of India CTRI/2014/05/004625 WHAT IS KNOWN: * Kangaroo mother care (KMC) reduces neonatal mortality, neonatal sepsis and improves growth outcome in VLBW infants. What is new: * Baby care by mother can be given safely in kangaroo ward from a weight of 1150 g in stable preterm infants without any adverse effects. PMID- 27562839 TI - Comparison of photopic negative response measurements in the time and time frequency domains. AB - PURPOSE: To compare measurements of the full-field photopic negative response (PhNR), as well as intra-subject variation in the PhNR, using time and time frequency domain analyses. METHODS: Full-field ERGs were recorded from 20 normally sighted subjects (aged 24-65 years) elicited by a long-wavelength pulse (3 cd s m-2) presented against a short-wavelength adapting field (12.5 cd m-2). Three to 10 waveforms were obtained from each subject, and each waveform was analyzed using standard time domain analyses of the PhNR, as well as a discrete wavelet transform (DWT) to extract time-frequency components that correspond to the PhNR. Three different measures of the PhNR were derived and compared: (1) amplitude at the PhNR trough; (2) amplitude at 72 ms following stimulus onset; (3) energy in the 11 Hz, 60-120 ms DWT frequency bin that corresponds to the PhNR. In addition, the effect of normalizing the PhNR by the b-wave was evaluated for each of the measures. Coefficients of variation (CVs) were computed for each definition to evaluate intra-subject variation. RESULTS: PhNR amplitudes measured at the trough and at 72 ms were significantly correlated (r = 0.88, p < 0.001). Additionally, PhNR energy derived by DWT was significantly correlated with the amplitude measured at the trough (r = 0.64, p = 0.002) and at 72 ms (r = 0.60, p = 0.005). Mean (+/-SD) intra-subject CVs were 26 % (15 %), 49 % (26 %), and 30 % (15 %), for measures at the trough, 72 ms, and DWT, respectively. Normalization by the b-wave amplitude (i.e., PhNR/b) had minimal effect on the intra-subject CVs, whereas normalization by the sum of the b-wave and PhNR amplitudes (i.e., PhNR/[b + PhNR]) substantially reduced the CVs for all three measures (mean CVs were less than 17 % for all conditions). CONCLUSIONS: Although each PhNR definition has advantages and disadvantages, all three metrics provide similar estimates of the PhNR. Intra-subject CVs, however, were relatively high for measurements made at 72 ms, indicating that definitions based on a fixed time point may introduce variability. The substantial decrease in intra-subject variation after normalization by the sum of the PhNR and b-wave amplitudes may be advantageous under some conditions. PMID- 27562840 TI - CD40L expression by CD4+ but not CD8+ T cells regulates antiviral immune responses in acute LCMV infection in mice. AB - CD40-CD40 ligand (CD40L) signaling plays multiple indispensable roles in cellular and humoral immunity. Impaired memory T-cell responses in the absence of CD40L have been well documented, but the requirement of this interaction for efficient priming of CD8+ T cells especially under inflammatory conditions has been under debate. In contrast to previous publications, we report here that virus-specific CD8+ T-cell responses as well as viral clearance are affected not only in the memory but also in the effector phase in CD40L-/- mice infected with lymphocytic choriomeningitis virus (LCMV) Armstrong strain. Interestingly, a considerable part of the LCMV-specific effector and memory T cells consists of CD40L+ CD8+ T cells. However, deficiency of CD40L in CD8+ T cells did influence neither the quantity nor the quality of primary T-cell responses in LCMV infection. Virus specific CD8+ T cells in conditional knockout mice, with a selective deletion of the CD40L in CD8+ T cells, were fully functional regarding cytokine production and efficient pathogen clearance. Thus, our results unambiguously demonstrate that while CD40L is critical to generate effective primary CD8+ T-cell responses also under inflammatory conditions, CD40L expression by CD8+ T cells themselves is dispensable in acute LCMV infection. PMID- 27562841 TI - Effect of irradiation on Akt signaling in atrophying skeletal muscle. AB - Muscle irradiation (IRR) exposure can accompany unloading during spaceflight or cancer treatment, and this has been shown to be sufficient by itself to induce skeletal muscle signaling associated with a remodeling response. Although protein kinase B/Akt has an established role in the regulation of muscle growth and metabolism, there is a limited understanding of how Akt signaling in unloaded skeletal muscle is affected by IRR. Therefore, we examined the combined effects of acute IRR and short-term unloading on muscle Akt signaling. Female C57BL/6 mice were subjected to load bearing or hindlimb suspension (HS) for 5 days (n = 6/group). A single, unilateral hindlimb IRR dose (0.5 Gy X-ray) was administered on day 3 Gastrocnemius muscle protein expression was examined. HS resulted in decreased AktT308 phosphorylation, whereas HS+IRR resulted in increased AktT308 phosphorylation above baseline. HS resulted in reduced AktS473 phosphorylation, which was rescued by HS+IRR. Interestingly, IRR alone resulted in increased phosphorylation of AktS473, but not that of AktT308 HS resulted in decreased mTORC1 signaling, and this suppression was not altered by IRR. Both IRR and HS resulted in increased MuRF-1 expression, whereas atrogin-1 expression was not affected by either condition. These results demonstrate that either IRR alone or when combined with HS can differentially affect Akt phosphorylation, but IRR did not disrupt suppressed mTORC1 signaling by HS. Collectively, these findings highlight that a single IRR dose is sufficient to disrupt the regulation of Akt signaling in atrophying skeletal muscle. PMID- 27562842 TI - Connective tissue regeneration in skeletal muscle after eccentric contraction induced injury. AB - Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury. PMID- 27562844 TI - It's in our interests not to be in conflict-of interest, that is. PMID- 27562843 TI - Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans. AB - In humans, acute aerobic exercise elicits a sustained postexercise vasodilation within previously active skeletal muscle. This response is dependent on activation of histamine H1 and H2 receptors, but the source of intramuscular histamine remains unclear. We tested the hypothesis that interstitial histamine in skeletal muscle would be increased with exercise and would be dependent on de novo formation via the inducible enzyme histidine decarboxylase and/or mast cell degranulation. Subjects performed 1 h of unilateral dynamic knee-extension exercise or sham (seated rest). We measured the interstitial histamine concentration and local blood flow (ethanol washout) via skeletal muscle microdialysis of the vastus lateralis. In some probes, we infused either alpha fluoromethylhistidine hydrochloride (alpha-FMH), a potent inhibitor of histidine decarboxylase, or histamine H1/H2-receptor blockers. We also measured interstitial tryptase concentrations, a biomarker of mast cell degranulation. Compared with preexercise, histamine was increased after exercise by a change (Delta) of 4.2 +/- 1.8 ng/ml (P < 0.05), but not when alpha-FMH was administered (Delta-0.3 +/- 1.3 ng/ml, P = 0.9). Likewise, local blood flow after exercise was reduced to preexercise levels by both alpha-FMH and H1/H2 blockade. In addition, tryptase was elevated during exercise by Delta6.8 +/- 1.1 ng/ml (P < 0.05). Taken together, these data suggest that interstitial histamine in skeletal muscle increases with exercise and results from both de novo formation and mast cell degranulation. This suggests that exercise produces an anaphylactoid signal, which affects recovery, and may influence skeletal muscle blood flow during exercise.NEW & NOTEWORTHY Blood flow to previously active skeletal muscle remains elevated following an acute bout of aerobic exercise and is dependent on activation of histamine H1 and H2 receptors. The intramuscular source of histamine that drives this response to exercise has not been identified. Using intramuscular microdialysis in exercising humans, we show both mast cell degranulation and formation of histamine by histidine decarboxylase contributes to the histamine-mediated vasodilation that occurs following a bout of aerobic exercise. PMID- 27562845 TI - Records of Bat Flies (Diptera: Nycteribiidae and Streblidae) in the Semi-Arid Caatinga in the State of Paraiba, Northeastern Brazil. AB - One of the largest gaps in the knowledge of ectoparasitic flies of the families Nycteribiidae and Streblidae in Brazil is the northeastern region, where most states do not have any record. Here, we present the first records of those two bat fly families for the state of Paraiba. We recorded a total of 10 species of five genera parasitizing eight bat species of four families. Trichobius diphyllae Wenzel (Streblidae) was the most abundant species, found parasitizing Diphylla ecaudata (Phyllostomidae), and T. dugesioides dugesioides Wenzel, the second, found on Trachops cirrhosus (Phyllostomidae). Three species were recorded for the first time in northeastern Brazil and seven species are new for the semi-arid Caatinga. We collected T. galei Wenzel and T. pallidus (Curran) on Natalus macrourus (Natalidae) and Furipterus horrens (Furipteridae), respectively, two endangered bat species, and the species-specific relationship with their hosts points out to some degree of vulnerability. In addition, we present information on host-parasite relationship, and data that extend the known geographic distribution of some species. PMID- 27562846 TI - Angiotensin Converting Enzyme Inhibitors Ameliorate Brain Inflammation Associated with Microglial Activation: Possible Implications for Alzheimer's Disease. AB - Angiotensin converting enzyme (ACE) converts Angiotensin I to a potent vasoconstrictor angiotensin II (ANG II). ACE inhibitors (ACEIs) are widely used for the management of hypertension. All components of the renin-angiotensin system (RAS) have also been identified in the brain. In addition to cytokines, neuromodulators such as ANG II can induce neuroinflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs and is thought to contribute to the propagation of the disease, increased levels of ANG II and ACE have been detected. However, the specific effect of ACEIs on neuroinflammation and AD remains obscure. The present study suggests that captopril and perindopril, centrally active ACEIs, may serve as modulators for microglial activation associated with AD. Our in vitro study investigated the effect of both ACEIs on nitric oxide (NO), tumor necrosis factor- alpha (TNF-alpha) release and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 microglia. Exposure of BV2 microglia to ACEIs significantly attenuated the LPS induced NO and TNF-alpha release. In vivo, short term intranasal administration of perindopril or captopril to 5 Familial AD (5XFAD) mice significantly reduced amyloid burden and CD11b expression (a microglial marker) or only CD11b expression respectively, in the cortex of 5XFAD. Long-term intranasal administration of captopril to mice reduced amyloid burden with no effect on CD11b expression. We provide evidence that intranasal delivery of ACEI may serve as an efficient alternative for their systemic administration, as it results in the attenuation of microglial accumulation and even the reduction of Amyloid beta (Abeta) plaques. PMID- 27562847 TI - Efficacy of N-Acetylserotonin and Melatonin in the EAE Model of Multiple Sclerosis. AB - Melatonin and N-acetylserotonin (NAS) are tryptophan metabolites that have potent anti-oxidant, anti-inflammatory and neuroprotective properties in several animal models of neurological injury and disease including multiple sclerosis (MS). The therapeutic effect of NAS has not been reported previously in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS. Using a MOG-peptide induced EAE mouse model we examined the effects of melatonin and NAS on clinical score, inflammatory markers, free radical generation, and sparing of axons, oligodendrocytes and myelin. We found that NAS and melatonin reduced clinical scores when administered prior to or after symptom onset. This effect was more pronounced when melatonin and NAS were administrated prior to symptom onset whereby the appearance of motor symptoms was significantly delayed. Activated microglia and CD4+ T-cells were increased in the white matter of untreated EAE mice, with a return to near control levels after melatonin or NAS treatment. The expression of the NADPH oxidase component p67phox and inducible nitric oxide synthase (iNOS) was increased in the EAE mice as compared with controls, and both drug treated groups had significant reductions in their expression. Melatonin and NAS treatment significantly reduced the loss of mature oligodendrocytes, demyelination and axonal injury. Both compounds also significantly attenuated iNOS induction and reactive oxygen species (ROS) generation in lipopolysaccharide-activated microglia in culture. Our results show for the first time the therapeutic effects of NAS and confirm previous reports on the effectiveness of melatonin in the EAE model of MS. PMID- 27562848 TI - Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain. AB - Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfalpha and decreased Trem2 mRNA, increased GFAP protein, and increased NFkappaB phosphorylation. Some of these effects were also observed in brains injected with mtDNA (decreased Trem2 mRNA, increased GFAP protein, and increased NFkappaB phosphorylation), and mtDNA injection also caused several unique changes including increased CSF1R protein and AKT phosphorylation. To further establish the potential relevance of this response to Alzheimer's disease (AD), a brain disorder characterized by neurodegeneration, mitochondrial dysfunction, and neuroinflammation we also measured App mRNA, APP protein, and Abeta1-42 levels. We found mitochondria (but not mtDNA) injections increased these parameters. Our data show that in the mouse brain extracellular mitochondria and its components can induce neuroinflammation, extracellular mtDNA or mtDNA-associated proteins can contribute to this effect, and mitochondria derived-DAMP molecules can influence AD-associated biomarkers. PMID- 27562850 TI - Council of Europe dismisses claim that abortion in Italy is harder because more doctors are objecting. PMID- 27562849 TI - MiR-139-5p is Increased in the Peripheral Blood of Patients with Prostate Cancer. AB - BACKGROUND: Emerging evidence suggested that microRNAs (miRNAs) play a causal role in cancer tumorigenesis. Aberrant expression of miRNA (miR)-139-5p has been observed in various types of cancers. The present study evaluated the relationship between miR-139-5p expression levels and prostate cancer (PCa), to assess the feasibility of using peripheral blood miR-139-5p as a potential non invasive biomarker for PCa. METHODS: Total RNA was extracted from peripheral whole blood samples from 45 PCa patients, 45 benign prostatic hyperplasia (BPH) patients and 50 healthy controls (HC). The expression of miR-139-5p was assessed by reverse transcription quantitative polymerase chain reaction. RESULTS: MiR-139 5p in peripheral blood was significantly higher in PCa patients than in patients with BPH and HC individuals (P<0.001). Higher miR-139-5p expression was observed to be associated with certain clinicopathological parameters, including PSA>20ng/ml (P<0.05), pathological tumor stage 3/4 (P<0.05) and Gleason score >7 (P<0.01). A receiver operating characteristic (ROC) curve analysis revealed that miR-139-5p distinguished PCa patients from BPH patients [area under the curve (AUC), 0.936; 95% CI, 0.878-0.993; P<0.001]. CONCLUSIONS: Peripheral blood miR 139-5p may be utilized as a potential novel non-invasive biomarker for PCa screening. PMID- 27562852 TI - Phenotyping at hot spots and tagging of QTLs conferring spot blotch resistance in bread wheat. AB - Spot blotch is a major foliar disease of wheat caused by Bipolaris sorokiniana in warm and humid environments of the world including South Asian countries. In India, it has a larger impact in Indo-Gangetic plains of the country. Therefore, the present study was undertaken to phenotype a mapping population at different hot spots of India and to detect quantitative trait loci (QTL) for resistance to spot blotch in wheat. For this study, 209 single seed descent (SSD) derived F8, F9, F10 recombinant inbred lines (RILs) of the cross 'Sonalika' (an Indian susceptible cultivar)/'BH 1146' (a Brazilian resistant cultivar) were assessed for spot blotch resistance at two hot spot locations (Coochbehar and Kalyani) for three years and for two years under controlled conditions in the polyhouse (Karnal). The population showed large variation in spot blotch reaction for disease severity in all the environments indicating polygenic nature of the disease. Microsatellite markers were used to create the linkage maps. Joint and/or individual year analysis by composite interval mapping (CIM) and likelihood of odds ratio (LOD) >2.1, detected two consistent QTLs mapped on chromosome 7BL and 7DL and these explained phenotypic variation of 11.4 percent and 9.5 percent over the years and locations, respectively. The resistance at these loci was contributed by the parent 'BH 1146' and shown to be independent of plant height and earliness. Besides, association of some agro-morphological traits has also been observed with percent disease severity. These identified genomic regions may be used in future wheat breeding programs through marker assisted selection for developing spot blotch resistant cultivars. PMID- 27562853 TI - Chromogenic media for MRSA diagnostics. AB - For the past decade, a number of chromogenic media for methicillin-resistance Staphylococcus aureus (MRSA) detection have been developed and applied, including Oxoid BrillianceTM MRSA, CHROMagarTM MRSA, BBLTM CHROMagarTM MRSA, MRSASelect and chromID MRSA. The advantages of these chromogenic media offers direct detection of visible staphylococcal colonies, coupled with the use of chromogenic enzymatic substrates that can be hydrolyzed by S. aureus to confirm species or strain identification. BBLTM CHROMagarTM MRSA and MRSASelect are designed for detection of nasal colonization by MRSA, while CHROMagarTM MRSA, Oxoid BrillianceTM MRSA and chromID MRSA are readily applied in bacterial screening. This review summarizes the characteristics, principles and capacities of these selective media, and focuses on comparison of different chromogenic media. PMID- 27562854 TI - A molecular genome scan to identify DNA segments associated with live weight in Japanese quail. AB - Japanese quail is an animal model in biological studies and also a commercial bird for eggs and meat production. This study was conducted to map quantitative trait loci (QTL) affecting live weight in Japanese quail. An F2 mapping population was developed by crossing two diverse lines (meat type and egg layer) of Japanese quail. A total number of 34 F1 and 422 F2 progeny were produced by reciprocal crossing of eight pairs of parental birds. All the birds from three generations were genotyped for SSR markers that were spread across all the autosomal linkage groups. The studied traits were hatching weight and live weights at 1-5 weeks of age. QTL analysis was conducted by the regression interval mapping. Significant QTL were detected on chromosomes 1, 2, 3 (chromosome-wide significant) and 5 (genome-wide significant, P < 0.05) for body weight. Although the additive effect of the detected QTL on chromosome 5 was significant, the dominance and imprinting effects were not significant. This finding is the first report of a genome-wide significant QTL associated with live weight in Japanese quail. Our results point out to candidate DNA regions affecting live weight, a trait of great economic relevance to the Japanese quail breeding. Although these results enhance our current knowledge about the genetic control of live weight in the Japanese quail, it should be noted that the initial QTL results from the experimental designs such as backcross or F2 cannot be applied directly to the breeding programs and require further validation within the commercial lines. PMID- 27562855 TI - Physical Activity Levels and Psychosis: A Mediation Analysis of Factors Influencing Physical Activity Target Achievement Among 204 186 People Across 46 Low- and Middle-Income Countries. AB - Physical activity (PA) can help reduce cardiovascular disease and premature mortality in people with psychosis. However, there is a paucity of representative data on PA in people with psychosis, especially from low- and middle-income countries (LMICs). Moreover, data on subclinical psychosis and PA is absent. This study explored whether complying with PA recommendations of 150 minutes of moderate-vigorous PA per week is related to: (1) psychotic symptoms without a psychosis diagnosis (subclinical psychosis); and (2) clinical psychosis (psychosis diagnosis). A total of 204 186 participants aged 18-64 years from 46 LMICs recruited via the World Health Survey were subdivided into those with (1) no psychosis diagnosis and no psychotic symptoms in the past 12 months (controls); (2) subclinical psychosis; and (3) psychosis diagnosis. People with a psychosis diagnosis had significantly higher odds for low PA in the overall sample (OR = 1.36; 95% CI = 1.04-1.78; P = .024) and among males (OR = 2.29; 95% CI = 1.57-3.34; P < .0001) but not females (OR = 0.93; 95% CI = 0.67-1.30; P = .6712). No difference was found among those with subclinical psychosis vs controls. Mediation analyses demonstrated that mobility difficulties explained the largest amount of low PA among males (18.5%) followed by self-care difficulties (16.3%), depression (16.1%), cognition (11.8%), pain and discomfort (11.4%), interpersonal activities (8.6%), sleep and energy (7.2%), and vision (3.0%). The results from the largest dataset on PA and psychosis and first in LMICs, found that psychosis diagnosis (especially among males) but not subclinical psychosis, is associated with physical inactivity. Population level interventions seeking to increase PA among people with psychosis may help improve health outcomes. PMID- 27562856 TI - Headache yesterday in Karnataka state, India: prevalence, impact and cost. AB - BACKGROUND: The Global Campaign against Headache has pioneered evaluation of the prevalence and impact of headache on the preceding day ("headache yesterday") as a new approach to the estimation of headache-attributed burden, avoiding recall error. We report its application in Karnataka State, southern India. METHODS: In a door-to-door survey, biologically unrelated adults (aged 18-65 years) were randomly sampled from urban and rural areas in and around Bengaluru and interviewed by trained researchers using a validated, structured questionnaire. Enquiry into headache applied ICHD-II diagnostic criteria and included questions about headache on the day preceding the interview (headache yesterday [HY]). RESULTS: There were 2329 participants (participation proportion 92.6 %; males 1141 [49.0 %], females 1188 [51.0 %]; mean age 38.0 [+/-12.7] years; 1103 [47.4 %] from rural areas, 1226 [52.6 %] urban). HY was reported by 138 participants (males 33 [2.9 %], females 105 [8.8 %]): the 1-day prevalence of headache was 5.9 %. Mean duration of HY was 7.0 +/- 8.5 h, so that 1.7 % of the population (5.9 % * 7.0/24), on average, had headache at any moment in time yesterday. Mean intensity on a scale of 1-3 was 2.0 [+/-0.8]. Lost productivity due to HY was reported by 83.3 % of participants with HY: 37.7 % able to do less than half of what they had planned and 13.0 % able to do nothing. Productivity loss at population level (being the productivity loss within the entire adult population, every single day, attributable to headache) was 3.0 %. CONCLUSIONS: This method of enquiry, free from recall error, confirmed a very high level of headache attributed burden in Karnataka: previous estimates based on 3-month recall may even have been too low. Until another study is done in the country, these are the best data for all India. They demonstrate need for action nationwide to mitigate this burden, and correct action will ultimately almost certainly be cost-saving. PMID- 27562857 TI - Estradiol Valerate and Remifemin ameliorate ovariectomy-induced decrease in a serotonin dorsal raphe-preoptic hypothalamus pathway in rats. AB - Perimenopausal syndromes begin as ovarian function ceases and the most common symptoms are hot flushes. Data indicate that the projections of serotonin to hypothalamus may be involved in the mechanism of hot flushes. Therefore, the aim of this study is to investigate the potential role of the serotonin dorsal raphe preoptic hypothalamus pathway for hot flushes in an animal model of menopause. We determined the changes in serotonin expression in the dorsal raphe (DR) and preoptic anterior hypothalamus (POAH) in ovariectomized rats. We also explored the therapeutical effects of estradiol valerate and Remifemin in this model. Eighty female Sprague-Dawley rats were randomly assigned to sham-operated (SHAM) group, ovariectomy (OVX) group with vehicle, ovariectomy with estradiol valerate treatment (OVX+E) group and ovariectomy with Remifemin (OVX+ICR) group. Serotonin expression was evaluated in the DR and POAH using immunofluorescence and quantified in the DR using an enzyme-linked immunosorbent assay (ELISA). Apoptosis was analyzed in the DR by TUNEL assay. The number of serotonin immunoreactive neurons and the level of serotonin expression in the DR decreased significantly following OVX compared to the SHAM group. No TUNEL-positive cells were detected in the DR in any group. In addition, following OVX, the number of serotonin-positive fibers decreased significantly in the ventromedial preoptic nucleus (VMPO), especially in the ventrolateral preoptic nucleus (VLPO). Treatment with either estradiol or Remifemin for 4 weeks countered the OVX induced decreases in serotonin levels in both the DR and the hypothalamus, with levels in the treated rats similar to those in the SHAM group. A fluorescently labeled retrograde tracer was injected into the VLPO at the 4-week time point. A significantly lower percentage of serotonin with CTB double-labeled neurons in CTB-labeled neurons was demonstrated after ovariectomy, and both estradiol and Remifemin countered this OVX-induced decrease. We conclude that serotonin pathway is changed after ovariectomy, including the serotonin synthesis in DR and serotonin fibers in PO/AH, both E and Remifemin have an equivalent therapeutic effect on it. PMID- 27562858 TI - First and second order stereology of hyaline cartilage: Application on mice femoral cartilage. AB - Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes matrix (chondrocyte clustering/dispersing), respectively. The mean+/-standard deviation of the cartilage volume, surface area, and thickness were 1.4+/-0.1mm3, 26.2+/-5.4mm2, and 52.8+/-6.7MUm, respectively. Besides, the mean number of chondrocytes was 680+/-200 (*103). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (p<0.03). Estimates of g(r) for the cells and matrix against the dipole distances, r, have been plotted. This plot showed that the chondrocytes and the matrix were neither dispersed nor clustered in the two study groups. Application of design-based stereological methods and also evaluation of spatial arrangement of the cartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. PMID- 27562859 TI - Integration of the musculature in the course "functional anatomy of the locomotor system"-Preparing medical students for the dissection course. AB - PURPOSE: To enhance the efficacy of the preclinical first-year course for medical and dental students 'functional anatomy of the locomotor system' (demo course) which serves as a preparation for the dissection course at the Friedrich Alexander University of Erlangen-Nurnberg, Germany. METHODS: The muscular system was integrated into the curriculum of the demo course. Moreover, the number of tutors was increased from around 5 to 15 for approximately 120 students. A detailed course agenda, which had been lacking hitherto, was developed for each course day. Extensive preparation and briefing of course tutors was introduced. Self-prepared questionnaires were applied to compare student attitudes towards the demo course before and after the restructuring process. Surveys were conducted at the end of the unchanged demo course, at the end of the dissection course in the following term (same students) and at the end of the restructured demo course. RESULTS: The mark given for overall course quality improved from 3 ("satisfactory") to 2 ("good"). The students felt significantly better prepared for the dissection course after the restructuring process, although they perceived the work load as more challenging in relation to the limited time available. They assessed the new course as better structured and stated that the muscular system had been important for the functional comprehension of the locomotor system. CONCLUSIONS: According to student opinion, the attempt to improve the demo course quality by providing a detailed course agenda and enhanced tutelage had been successful. As expected, the musculature is critical to functional understanding of the locomotor system. PMID- 27562860 TI - Use of calcofluor-blue brightener for the diagnosis of Pneumocystis jirovecii pneumonia in bronchial-alveolar lavage fluids: A single-center prospective study. AB - The biological diagnosis of Pneumocystis jirovecii pneumonia (PjP) is based on the investigation of respiratory fluids by conventional staining methods and/or molecular biology. Diagnostic performance of an in-house technique based on calcofluor-blue brightener for the direct detection of P. jirovecii cysts was prospectively assessed in bronchial-alveolar lavage fluids (BALF) from patients with a suspected PjP infection over a three-year period in a single center: the diagnostic yield was compared to that of a commercial kit based on monoclonal immunofluorescence assay (IFA) on replicate smears. May-Grunwald Giemsa (MGG) staining and quantitative Polymerase Chain Reaction (qPCR) were also performed. The gold standard for each patient was the definitive diagnosis of PjP infection by an independent committee based on clinical, radiological, and biological data. Overall, 481 BALF were assessed: 42 were found to be positive for the detection of P. jirovecii by at least one laboratory technique, but only 35 were actually judged to be in agreement with the definitive diagnosis of PjP infection. The sensitivity of the calcofluor-blue brightener technique was 74.3% vs. 60.0%, 34.6%, and 82.9% for IFA, MGG, and qPCR, respectively; and its specificity was 99.6% vs. 99.3%, 100.0%, and 99.4% for IFA, MGG, and qPCR. No technique was shown to be statistically superior to calcofluor-blue brightener. Further validation of the test through multicenter studies is now required, but in light of its low cost and easy preparation, the use of calcofluor-blue brightener in BALF appears to be a valuable alternative method for the routine first-line diagnosis of PjP infection. PMID- 27562861 TI - Breakthrough invasive fungal diseases during voriconazole treatment for aspergillosis: A 5-year retrospective cohort study. AB - Breakthrough invasive fungal diseases (bIFDs) during voriconazole treatment are concerning, as they are associated with high rates of mortality and pathogen distribution. To evaluate the prevalence, incidence, patient characteristics, including IFD events, and overall mortality of bIFDs during voriconazole treatment for invasive aspergillosis (IA). We retrospectively analyzed the medical records of consecutive patients who had undergone voriconazole treatment for IA and who had bIFD events between January 2011 and December 2015. Eleven bIFD events occurred in 9 patients. The prevalence and incidence of bIFDs were 2.25% (9/368) and 0.22 cases per year, respectively. Overall mortality was 44.4% (4/9). The severity of the illness and persistence of immunodeficiency, mixed infection, and low concentration of the treatment drug at the site of infection were identified as possible causes of bIFDs. Seven of 11 events (63.6%) required continued voriconazole treatment with drug level monitoring. In 4 (36.3%) cases, the treatment was changed to liposomal amphotericin B. Two cases resulted in surgical resection (18.2%). Clinicians should be aware that bIFDs during voriconazole treatment for IA can occur, and active therapeutic approaches are required in these cases. PMID- 27562862 TI - The anti-Aspergillus drug pipeline: Is the glass half full or empty? AB - Aspergillosis has emerged as important human mycoses, in view of the ever expanding population at risk. The emergence of resistance to the most commonly used drugs for aspergillosis, the azoles, the mediocre activity, and frequent toxicity of the current antifungal armamentarium, support the need for development of novel antifungals for treatment of this disease. In this minireview, we describe recent efforts by small drug companies and University research labs to develop novel therapies for invasive aspergillus infections. We specifically discuss four small-molecule antifungals (T-2307, E1210/APX001, ASP2397, and F901318) with novel modes-of-action, which are currently entering phase I clinical trials. In addition, we provide a nonexhaustive discussion of some interesting, yet early developments in the quest for improved therapeutic strategies such as (i) novel formulations of amphotericin B including AMB nanoparticle suspensions and AMB-arabinogalactan or AMB-PEG conjugates that show low toxicity and high efficacy in preclinical animal models, (ii) repurposed drugs that synergize with existing antifungals (clozafimine, trichostatin A, MGCD290, geldanamycin, tacrolimus, cyclosporin), (iii) natural products (psoriasin, humidimycin), and (iv) immunotherapy using adoptive transfer of activated immune cells with antifungal activity. We argue that despite the plethora of candidates, the extremely low success rates of drug development leading to clinically useful drugs reinforces the need for continued clinical reliance on mainstream antifungals and their improved derivatives. PMID- 27562863 TI - The cytotoxic T cells may contribute to the in situ immune response in Jorge Lobo's Disease human lesions. AB - Jorge Lobo's Disease (JLD) is a cutaneous chronic granulomatous disease caused by the pathogenic fungus Lacazia loboi. It is characterized by a granulomatous reaction with multinucleated giant cells and high number of fungal cells. In order to contribute to the comprehension of immune mechanisms in JLD human lesions, we studied the cytotoxic immune response, focusing on TCD8+ and NK cells, and granzyme B. Forty skin biopsies of lower limbs were selected and an immunohistochemistry protocol was developed to detect CD8+ T cells, NK cells and Granzyme B. In order to compare the cellular populations, we also performed a protocol to visualize TCD4+ cells. Immunolabeled cells were quantified in nine randomized fields in the dermis. Lesions were characterized by inflammatory infiltrate of macrophages, lymphocytes, epithelioid and multinucleated giant cells with intense number of fungal forms. There was a prevalence of CD8 over CD4 cells, followed by NK cells. Our results suggest that in JLD the cytotoxic immune response could represent another important mechanism to control Lacazia loboi infection. We may suggest that, although CD4+ T cells are essential for host defense in JLD, CD8+ T cells could play a role in the elimination of the fungus. PMID- 27562864 TI - Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy. AB - Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles - EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. PMID- 27562865 TI - MiR-26a and miR-138 block the G1/S transition by targeting the cell cycle regulating network in prostate cancer cells. AB - PURPOSE: The tumor-suppressive microRNAs miR-26a and miR-138 are significantly down-regulated in prostate cancer (PCa) and have been identified as direct regulators of enhancer of zeste homolog 2 (EZH2), which is a known oncogene in PCa. In the present study, the influence of miR-26a and miR-138 on EZH2 and cellular function including the impact on the cell cycle regulating network was evaluated in PCa cells. METHODS: PC-3 and DU-145 PCa cells were transfected with 100 nM of miRNA mimics, siRNA against EZH2 (siR-EZH2) or control constructs for 4 h. Analyses of gene expression and cellular function were conducted 48 h after transfection. RESULTS: Both miRNAs influenced the EZH2 expression and activity only marginally, whereas siR-EZH2 led to a notable decrease of the EZH2 expression and activity. Both miRNAs inhibited short- and/or long-term proliferation of PCa cells but showed no effect on viability and apoptosis. In PC 3 cells, miR-26a and miR-138 caused a significant surplus of cells in the G0/G1 phase of 6 and 12 %, respectively, thus blocking the G1/S-phase transition. Treatment with siR-EZH2 was without substantial influence on cellular function and cell cycle. Therefore, alternative target genes involved in cell cycle regulation were identified in silico. MiR-26a significantly diminished the expression of its targets CCNE1, CCNE2 and CDK6, whereas CCND1, CCND3 and CDK6 were suppressed by their regulator miR-138. CONCLUSIONS: The present findings suggest an anti-proliferative role for miR-26a and miR-138 in PCa by blocking the G1/S-phase transition independent of EZH2 but via a concerted inhibition of crucial cell cycle regulators. PMID- 27562866 TI - Heterogeneous incidence and propagation of spreading depolarizations. AB - Spreading depolarizations are implicated in a diverse set of neurologic diseases. They are unusual forms of nervous system activity in that they propagate very slowly and approximately concentrically, apparently not respecting the anatomic, synaptic, functional, or vascular architecture of the brain. However, there is evidence that spreading depolarizations are not truly concentric, isotropic, or homogeneous, either in space or in time. Here we present evidence from KCl induced spreading depolarizations, in mouse and rat, in vivo and in vitro, showing the great variability that these depolarizations can exhibit. This variability can help inform the mechanistic understanding of spreading depolarizations, and it has implications for their phenomenology in neurologic disease. PMID- 27562867 TI - Metabolic demands of neural-hemodynamic associated and disassociated areas in brain. AB - Interpretation of regional blood oxygenation level-dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is contingent on whether local field potential (LFP) and multi-unit activity (MUA) is either dissociated or associated. To examine whether neural-hemodynamic associated and dissociated areas have different metabolic demands, we recorded sensory-evoked responses of BOLD signal, blood flow (CBF), and blood volume (CBV), which with calibrated fMRI provided oxidative metabolism (CMRO2) from rat's ventral posterolateral thalamic nucleus (VPL) and somatosensory forelimb cortex (S1FL) and compared these neuroimaging signals to neurophysiological recordings. MUA faithfully recorded evoked latency differences between VPL and S1FL because evoked MUA in these regions were similar in magnitude. Since evoked LFP was significantly attenuated in VPL, we extracted the time courses of the weaker thalamic LFP to compare with the stronger cortical LFP using wavelet transform. BOLD and CBV responses were greater in S1FL than in VPL, similar to LFP regional differences. CBF and CMRO2 responses were both comparably larger in S1FL and VPL. Despite different levels of CBF-CMRO2 and LFP-MUA couplings in VPL and S1FL, the CMRO2 was well matched with MUA in both regions. These results suggest that neural-hemodynamic associated and dissociated areas in VPL and S1FL can have similar metabolic demands. PMID- 27562868 TI - Adding checkpoint inhibitors to tyrosine kinase inhibitors targeting EGFR/ALK in non-small cell lung cancer: a new therapeutic strategy. AB - After the massive approval of checkpoint inhibitors in the treatment of numerous malignancies and settings, checkpoint inhibitors-based combination therapies are emerging as a new therapeutic modality. Nivolumab and pembrolizumab (anti-PD1 agents) were recently approved as second-line treatment in NSCLC after progression on platinum-doublets. In parallel, targeting EGFR/ALK in NSCLC using tyrosine kinase inhibitors (TKI) demonstrated remarkable outcomes and was approved as standard treatment, in patients with EGFR mutation or ALK rearrangement. Combining TKI targeting EGFR/ALK with checkpoint inhibitors seems a promising therapeutic option and is being evaluated in different trials. We aimed in this paper to elucidate the rationale behind this combination, to report the premilinary results of ongoing trials evaluating this association and finally, to discuss briefly the possible future indication of this treatment modality. PMID- 27562869 TI - Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer. AB - PURPOSE: Serum markers with increased sensitivity and specificity for endometrial cancer are required. To date, no good marker has met this standard. The aims of our study were to evaluate the utility of tumor markers HE4, CA125, CA724, and CA19-9 as potential markers in patients diagnosed with endometrial cancer. METHODS: Blood samples from 105 patients with endometrial cancer and 87 healthy women were analyzed by Roche electrochemiluminescent immunoassay, and serum values were measured for the following biomarkers: HE4, CA125, CA724, and CA19-9. RESULTS: Serum HE4, CA125, CA724, and CA19-9 concentrations were significantly higher in patients with endometrial cancer, compared with controls ( P < .001). In the receiver operating characteristic analysis, the area under the curve value for combination of HE4, CA125, CA724, and CA19-9 was 82.1% (95% confidence interval: 75.3%-86.2%), the maximum area of the test groups. For all stages of patients with endometrial cancer, HE4 had higher sensitivity (58%), positive predictive value (60%), and negative predictive value (67%) than any other single tumor marker, and in the combination of HE4, CA125, CA724, and CA19-9, the sensitivity and positive predictive values reached 59.1% and 88%, respectively. Meanwhile, the receiver operating characteristic area under the curve of the combination of the 4 markers was significantly increased than any other group, either in stage I or in stage II to IV cases. HE4 and CA125 both correlate with advanced age; in addition, HE4 was related to pathology subtypes and positive adnexal involvement, CA125 was related to International Federation of Gynecology and Obstetrics stage, CA19-9 was related to International Federation of Gynecology and Obstetrics stage, and CA724 was correlated with positive lymph node. CONCLUSION: Combination of HE4, CA125, CA724, and CA19-9 has the highest value in diagnosing endometrial cancer, and they can be a useful tissue immune marker for patients with endometrial cancer. PMID- 27562874 TI - Anthropogenic N deposition increases soil organic matter accumulation without altering its biochemical composition. AB - Accumulating evidence indicates that future rates of atmospheric N deposition have the potential to increase soil C storage by reducing the decay of plant litter and soil organic matter (SOM). Although the microbial mechanism underlying this response is not well understood, a decline in decay could alter the amount, as well as biochemical composition of SOM. Here, we used size-density fractionation and solid-state 13 C-NMR spectroscopy to explore the extent to which declines in microbial decay in a long-term (ca. 20 yrs.) N deposition experiment have altered the biochemical composition of forest floor, bulk mineral soil, as well as free and occluded particulate organic matter. Significant amounts of organic matter have accumulated in occluded particulate organic matter (~20%; oPOM); however, experimental N deposition had not altered the abundance of carboxyl, aryl, alkyl, or O/N-alkyl C in forest floor, bulk mineral soil, or any soil fraction. These observations suggest that biochemically equivalent organic matter has accumulated in oPOM at a greater rate under experimental N deposition, relative to the ambient treatment. Although we do not understand the process by which experimental N deposition has fostered the occlusion of organic matter by mineral soil particles, our results highlight the importance of interactions among the products of microbial decay and the chemical and physical properties of silt and clay particles that occlude organic matter from microbial attack. Because oPOM can reside in soils for decades to centuries, organic matter accumulating under future rates of anthropogenic N deposition could remain in soil for long periods of time. If temperate forest soils in the Northern Hemisphere respond like those in our experiment, then unabated deposition of anthropogenic N from the atmosphere has the potential to foster greater soil C storage, especially in fine-texture forest soils. PMID- 27562873 TI - Drug-Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV. AB - Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with HIV worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability, and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized. PMID- 27562875 TI - Higher protein intake is associated with increased risk for incident end-stage renal disease among blacks with diabetes in the Southern Community Cohort Study. AB - BACKGROUND AND AIMS: Diabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes. METHODS AND RESULTS: We conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002-2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (+/-SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 +/- 3.3 vs. 15.1 +/- 3.1%, P < 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02-1.10) for blacks with diabetes, 1.02 (0.98-1.06) for blacks without diabetes, 0.99 (0.90-1.09) for whites with diabetes and 0.94 (0.84-1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17-2.65). CONCLUSION: Our results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed. PMID- 27562876 TI - Prevalence and incidence of toxoplasmosis: a retrospective analysis of mother child examinations, Styria, Austria, 1995 to 2012. AB - In Austria, mandatory screening for the prevention of congenital toxoplasmosis stipulates a serological test for antibodies against Toxoplasma gondii as early as possible in pregnancy. In the case of a seronegative result, subsequent tests at intervals of 8 weeks are requested. We analysed serological data from Styria, an Austrian federal state, to determine the seroprevalence and incidence of Toxoplasma infections. The study included 353,599 tests from 103,316 women during 158,571 pregnancies from 1995 to 2012. The age-adjusted seroprevalence decreased from 43.3% in 1995 to 31.5% in 2012, with a yearly decline of 0.84% (95% confidence interval (CI): 0. 79 -0.88). The intergravid incidence showed an annual decrease of 4.2%. The average yearly incidence of intragravid and intergravid seroconversions was 0.52% (95% CI 0.45-0.61) and 0.72% (95% CI 0.67 0.77), respectively. If the difference between these rates (p < 0.001) can be explained by the effect of primary prevention such as avoiding raw meat and taking hygiene precautions when encountering cats or preparing vegetables, only ca two of seven (28%) infections were avoided by hygiene measures taken by pregnant women. Primary prevention may therefore have its limits. PMID- 27562877 TI - Bizarre cause for abdominal pain in a young female. PMID- 27562878 TI - Third Places for Health Promotion with Older Adults: Using the Consolidated Framework for Implementation Research to Enhance Program Implementation and Evaluation. AB - This study extends the concept of third places to include community sites where older adults gather, often for meals or companionship. The Consolidated Framework for Implementation Research guided program implementation and evaluation. Depending upon health promotion program needs, the physical infrastructure of a site is important, but a supportive director (champion) can often overcome identified deficits. Senior centers may be locally classified into four types based upon eligibility requirements of residents in affiliated housing and services offered. Participants who attend these centers differ in important ways across types by most sociodemographic as well as certain health and health care characteristics. PMID- 27562879 TI - Monoclonal antibodies for the treatment of osteoarthritis. AB - INTRODUCTION: Osteoarthritis (OA) is a multifactorial chronic joint disease, and so far, there are no approved disease-modifying anti-OA drugs (DMOADs). There is an urgent need to develop therapies for different phenotypes of OA. Monoclonal antibodies (mAb) may slow structural progression, control inflammation and relieve pain, and thus have the potential to be DMOADs. Areas covered: In this review, the authors searched the literature on PubMed, EMBASE and the Cochrane Library using keywords, including mAbs, biological agents, OA and osteoarthritis, electronically up to May 2016. They also included abstracts of international conferences. Furthermore, they reviewed experimental and clinical studies of various mAbs targeting different pathological mechanisms of OA, including ADAMTS, Interleukine-1, tumour necrosis factor, never growth factor and vascular endothelial growth factor. Expert opinion: MAbs for the treatment of OA are under intense investigation and the results for some mAbs (e.g., anti-nerve growth factor mAbs, anti- vascular endothelial growth factor mAbs) are promising. The authors believe that mAb therapy can be a targeted therapeutic approach for the treatment of OA. Future clinical trials are required to evaluate the therapeutic efficacy of these agents by the appropriate selection of specific phenotype for targeted therapy based on the mechanism of drug action. PMID- 27562880 TI - Processing cost and its consequences. AB - I focus on two challenges that processing-based theories of language must confront: the need to explain why language has the particular properties that it does, and the need to explain why processing pressures are manifested in the particular way that they are. I discuss these matters with reference to two illustrative phenomena: proximity effects in word order and a constraint on contraction. PMID- 27562881 TI - Rapeseed napin and cruciferin are readily digested by poultry. AB - Rapeseed proteins have been considered as being poorly digestible in the gut of non-ruminants. The aim of the study was to assess the digestibility of napin and cruciferin in ileal digesta of broiler chickens, testing sixteen samples of rapeseed co-products with protein levels ranging from 293 g/kg to 560 g/kg dry matter. Each sample was included into a semi-synthetic diet at a rate of 500 g/kg and evaluated with broiler chickens in a randomised design. Dietary and ileal digesta proteins were extracted and identified by gel-based liquid chromatography tandem mass spectrometry (LC-MS/MS). Three isomers of napin (a 2S albumin) and nine cruciferins (an 11S globulin) were identified in the rapeseed co-products, whereas six endogenous enzymes such as trypsin (I-P1, II-P29), chymotrypsin (elastase and precursor), carboxypeptidase B and alpha-amylase were found in the ileal digesta. It is concluded that as none of the rapeseed proteins were detected in the ileal digesta, rapeseed proteins can be readily digested by broiler chickens, irrespective of the protein content in the diet. PMID- 27562882 TI - Synthesis of Co(II)-NO(-) Complexes and Their Reactivity as a Source of Nitroxyl. AB - Metal-nitroxyl (M-HNO/M-NO(-)) coordination units are found in denitrification enzymes of the global nitrogen cycle, and free HNO exhibits pharmacological properties related to cardiovascular physiology that are distinct from nitric oxide (NO). To elucidate the properties that control the binding and release of coordinated nitroxyl or its anion at these biological metal sites, we synthesized {CoNO}(8) (1, 2) and {CoNO}(9) (3, 4) complexes that contain diimine-dipyrrolide supporting ligands. Experimental (NMR, IR, MS, EPR, XAS, XRD) and computational data (DFT) support an oxidation state assignment for 3 and 4 of high spin Co(II) (SCo = 3/2) coordinated to (3)NO(-) (SNO = 1) for Stot = 1/2. As suggested by DFT, upon protonation, a spin transition occurs to generate a putative low spin Co(II)-(1)HNO (SCo = Stot = 1/2); the Co-NO bond is ~0.2 A longer, more labile, and facilitates the release of HNO. This property was confirmed experimentally through the detection and quantification of N2O (~70% yield), a byproduct of the established HNO self-reaction (2HNO -> N2O + H2O). Additionally, 3 and 4 function as HNO donors in aqueous media at pH 7.4 and react with known HNO targets, such as a water-soluble Mn(III)-porphyrin ([Mn(III)(TPPS)](3-); TPPS = meso-tetrakis(4 sulfonatophenyl)porphyrinate) and ferric myoglobin (metMb) to quantitatively yield [Mn(TPPS)(NO)](4-) and MbNO, respectively. PMID- 27562884 TI - Where Medical Education matters. PMID- 27562885 TI - Revisiting 'Assessing professional competence: from methods to programmes'. PMID- 27562886 TI - Integration, continuity and longitudinality: the 'what' that makes patient centred learning in clinical clerkships. PMID- 27562887 TI - Effective feedback and the educational alliance. PMID- 27562888 TI - Context, time, and building relationships: bringing in situ feedback into the conversation. PMID- 27562889 TI - When I say ... leadership. PMID- 27562890 TI - A systematic review of assessment and intervention strategies for effective clinical communication in culturally and linguistically diverse students. AB - OBJECTIVE: Culturally and linguistically diverse (CALD) students often experience difficulties with the clinical communication skills that are essential for successful interactions in the workplace. However, there is little evidence on the effectiveness of assessment and intervention strategies for this population. The two aims of this study were: to evaluate the effectiveness of assessment tools in identifying and describing the clinical communication difficulties of CALD health care students; and to determine whether communication programmes improved their clinical communication skills. METHODS: Systematic review based on the Cochrane protocol. Articles were identified through a search of established databases using MeSH and key search terms. Studies published in English from 1990 to March 2015 were included if they described assessment strategies or a training programme for communication skills of CALD students. Studies were excluded if they did not describe implementation of a specific assessment or intervention programme. Data were extracted independently by the first author and verified by the second author. Quality was measured by the Best Evidence Medical Education guide and the Educational Interventions Critical Appraisal Tool. The Kirkpatrick hierarchy was used to measure impact. Meta-analysis was not conducted because of the heterogeneity of programme design and outcome measures. RESULTS: One hundred and twenty-nine articles met the criteria for full text review. Eighty-six articles were excluded. Thirteen articles addressing assessment and 30 articles reporting on communication training programmes were included in this review. Assessment tools used rubrics and rating scales effectively. Intervention studies focused on speech and language skills (n = 20), interpersonal skills (n = 7) and faculty-level support (n = 5). Although 17 studies reported positive findings on student satisfaction, only eight reported improved skills post-training. CONCLUSIONS: The development of effective assessment and intervention programmes should have an integrated design and include specific outcome measures to increase educational impact. PMID- 27562891 TI - Dimensions of integration, continuity and longitudinality in clinical clerkships. AB - CONTEXT: Over the past few decades, longitudinal integrated clerkships (LICs) have been proposed to address many perceived short-coming of traditional block clerkships. This growing interest in LICs has raised broader questions regarding the role of integration, continuity and longitudinality in medical education. A study with complementary theoretical and empirical dimensions was conducted to derive a more precise way of defining these three underlying concepts within the design of medical education curricula. METHODS: The theoretical dimension involved a thematic review of the literature on integration, continuity and longitudinality in medical education. The empirical dimension surveyed all 17 Canadian medical schools on how they have operationalised integration, continuity and longitudinality in their undergraduate programmes. The two dimensions were iteratively synthesised to explore the meaning and expression of integration, continuity and longitudinality in medical education curriculum design. RESULTS: Integration, continuity and longitudinality were expressed in many ways and forms, including: integration of clinical disciplines, combined horizontal integration and vertical integration, and programme-level integration. Types of continuity included: continuity of patients, continuity of teaching, continuity of location and peer continuity. Longitudinality focused on connected or repeating episodes of training or on connecting activities, such as encounter logging across educational episodes. Twelve of the 17 schools were running an LIC of some kind, although only one school had a mandatory LIC experience. An ordinal scale of uses of integration, continuity and longitudinality during clerkships was developed, and new definitions of these concepts in the clerkship context were generated. CONCLUSIONS: Different clerkship designs embodied different forms and levels of integration, continuity and longitudinality. A dichotomous view of LICs and rotation-based clerkships was found not to represent current practices in Canada, which instead tended to fall along a continuum of integration, continuity and longitudinality. PMID- 27562893 TI - Feedback and the educational alliance: examining credibility judgements and their consequences. AB - CONTEXT: Several recent studies have documented the fact that, in considering feedback, learners are actively making credibility judgements about the feedback and its source. Yet few have intentionally explored such judgements to gain a deeper understanding of how the process works or how these judgements might interact to influence engagement with and interpretation of feedback. Using the educational alliance framework, we sought to elaborate an understanding of learners' credibility judgements and their consequences. METHODS: Using constructivist grounded theory we conducted semi-structured interviews with psychiatry residents. We used a theoretical sampling approach that invited participants with diverse scores based on a previously published feedback survey and an investigator-developed educational alliance inventory. Consistent with the principles of grounded theory analysis, data were collected and analysed in an iterative process to identify themes. RESULTS: Participants depicted themselves as actively contemplating feedback and considering it thoughtfully in light of complex judgements regarding their supervisor, the relationship with their supervisor and the larger context in which the feedback interactions were occurring. These judgements focused on the supervisor's credibility both as a clinician and as a partner in the educational alliance. The educational alliance is judged by trainees in relation to the supervisor's engagement as an educator, commitment to promoting growth of residents and positive attitude toward them. CONCLUSIONS: Our findings suggest that credibility is a multifaceted judgement that occurs not only at the moment of the feedback interaction but early in and throughout an educational relationship. It not only affects a learner's engagement with a particular piece of feedback at the moment of delivery, but also has consequences for future engagement with (or avoidance of) further learning interactions with the supervisor. These findings can help medical educators develop a more meaningful understanding of the context in which feedback takes place. PMID- 27562894 TI - Investigating conditions for meaningful feedback in the context of an evidence based feedback programme. AB - CONTEXT: We developed, implemented and evaluated an evidence-based programme of feedback designed to address limitations identified in the current literature. OBJECTIVES: We sought to advance understanding about how and why feedback processes might be more effective in clinical education. METHODS: Three faculty members and nine first-year internal medicine residents participated in the pilot programme. To counter challenges identified in the literature, feedback was based on direct observation, grounded in longitudinal faculty-resident relationships, and devoid of summative assessment. We used a qualitative case study design to address three research questions: (i) What benefits did the participants describe? (ii) What elements of the programme facilitated these benefits? (iii) What were the limitations and challenges of the programme? Collected data included audiotapes of interactions between faculty members and residents, field notes written during observations, and semi-structured interviews and focus groups with resident participants. Data analysis moved cyclically and iteratively through inductive and deductive analysis. RESULTS: Residents described benefits relating to their ways of working (clinical skills), ways of learning (accountability for learning) and ways of feeling (emotional well-being). According to participants, specific elements of the programme that achieved these benefits included the direct observation of authentic clinical work, the longitudinal relationship with a faculty member and the emergence of feedback as a conversation between the faculty member and learner. CONCLUSIONS: We conclude that the conditions established within our pilot feedback programme influenced the learning culture for first-year internal medicine residents by grounding direct observation in authentic clinical work and setting the observations in the context of a longitudinal, non-assessment-based relationship between a faculty member and resident. These conditions appeared to influence residents' participation in the feedback process, their ways of approaching their daily clinical work, their emotional well-being and their engagement in their own learning. PMID- 27562892 TI - A typology of longitudinal integrated clerkships. AB - CONTEXT: Longitudinal integrated clerkships (LICs) represent a model of the structural redesign of clinical education that is growing in the USA, Canada, Australia and South Africa. By contrast with time-limited traditional block rotations, medical students in LICs provide comprehensive care of patients and populations in continuing learning relationships over time and across disciplines and venues. The evidence base for LICs reveals transformational professional and workforce outcomes derived from a number of small institution-specific studies. OBJECTIVES: This study is the first from an international collaborative formed to study the processes and outcomes of LICs across multiple institutions in different countries. It aims to establish a baseline reference typology to inform further research in this field. METHODS: Data on all LIC and LIC-like programmes known to the members of the international Consortium of Longitudinal Integrated Clerkships were collected using a survey tool developed through a Delphi process and subsequently analysed. Data were collected from 54 programmes, 44 medical schools, seven countries and over 15 000 student-years of LIC-like curricula. RESULTS: Wide variation in programme length, student numbers, health care settings and principal supervision was found. Three distinct typological programme clusters were identified and named according to programme length and discipline coverage: Comprehensive LICs; Blended LICs, and LIC-like Amalgamative Clerkships. Two major approaches emerged in terms of the sizes of communities and types of clinical supervision. These referred to programmes based in smaller communities with mainly family physicians or general practitioners as clinical supervisors, and those in more urban settings in which subspecialists were more prevalent. CONCLUSIONS: Three distinct LIC clusters are classified. These provide a foundational reference point for future studies on the processes and outcomes of LICs. The study also exemplifies a collaborative approach to medical education research that focuses on typology rather than on individual programme or context. PMID- 27562895 TI - Thrive or overload? The effect of task complexity on novices' simulation-based learning. AB - CONTEXT: Fidelity is widely viewed as an important element of simulation instructional design based on its purported relationship with transfer of learning. However, higher levels of fidelity may increase task complexity to a point at which novices' cognitive resources become overloaded. OBJECTIVES: In this experiment, we investigate the effects of variations in task complexity on novices' cognitive load and learning during simulation-based procedural skills training. METHODS: Thirty-eight medical students were randomly assigned to simulation training on a simple or complex lumbar puncture (LP) task. Participants completed four practice trials on this task (skill acquisition). After 10 days of rest, all participants completed one additional trial on their assigned task (retention) and one trial on a 'very complex' simulation designed to be similar to the complex task (transfer). We assessed LP performance and cognitive load on each trial using multiple measures. RESULTS: In both groups, LP performance improved significantly during skill acquisition (p <= 0.047, f = 0.29 0.96) and was maintained at retention. The simple task group demonstrated superior performance compared with the complex task group throughout these phases (p <= 0.002, d = 1.13-2.31). Cognitive load declined significantly in the simple task group (p < 0.009, f = 0.48-0.76), but not in the complex task group during skill acquisition, and remained lower at retention (p <= 0.024, d = 0.78-1.39). Between retention and transfer, LP performance declined and cognitive load increased in the simple task group, whereas both remained stable in the complex task group. At transfer, no group differences were observed in LP performance and cognitive load, except that the simple task group made significantly fewer breaches of sterility (p = 0.023, d = 0.80). CONCLUSIONS: Reduced task complexity was associated with superior LP performance and lower cognitive load during skill acquisition and retention, but mixed results on transfer to a more complex task. These results indicate that task complexity is an important factor that may mediate (via cognitive overload) the relationship between instructional design elements (e.g. fidelity) and simulation-based learning outcomes. PMID- 27562897 TI - Cognitive load measures mainly have meaning when they are combined with learning outcome measures. PMID- 27562896 TI - Influence of learner knowledge and case complexity on handover accuracy and cognitive load: results from a simulation study. AB - CONTEXT: The handover represents a high-risk event in which errors are common and lead to patient harm. A better understanding of the cognitive mechanisms of handover errors is essential to improving handover education and practice. OBJECTIVES: This paper reports on an experiment conducted to study the effects of learner knowledge, case complexity (i.e. cases with or without a clear diagnosis) and their interaction on handover accuracy and cognitive load. METHODS: Participants were 52 Dutch medical students in Years 2 and 6. The experiment employed a repeated-measures design with two explanatory variables: case complexity (simple or complex) as the within-subject variable, and learner knowledge (as indicated by illness script maturity) as the between-subject covariate. The dependent variables were handover accuracy and cognitive load. Each participant performed a total of four simulated handovers involving two simple cases and two complex cases. RESULTS: Higher illness script maturity predicted increased handover accuracy (p < 0.001) and lower cognitive load (p = 0.007). Case complexity did not independently affect either outcome. For handover accuracy, there was no interaction between case complexity and illness script maturity. For cognitive load, there was an interaction effect between illness script maturity and case complexity, indicating that more mature illness scripts reduced cognitive load less in complex cases than in simple cases. CONCLUSIONS: Students with more mature illness scripts performed more accurate handovers and experienced lower cognitive load. For cognitive load, these effects were more pronounced in simple than complex cases. If replicated, these findings suggest that handover curricula and protocols should provide support that varies according to the knowledge of the trainee. PMID- 27562898 TI - Cord and blood levels of newborn IgE: Correlation, role and influence of maternal IgE. AB - The role of cord blood immunoglobulin E (IgE) levels in predicting the development of atopy has been widely investigated. The aim of the study was to evaluate the correlation between serum and cord blood total IgE in newborns and the possible influence of the atopic status of the mother on them. It was also investigated the possible role of gestational age on neonatal total IgE levels. We considered 763 deliveries, 724>=37 weeks of gestation and 39<37 weeks of gestation. 14% of mothers (13.7% at term, 15.4% preterm) showed high total IgE levels. The results showed a significant correlation between serum and cord IgE levels both in preterm and term newborns. The data revealed also that mother's total IgE levels affect both neonatal serum and cord total IgE levels. For the latters we also found child gender as an additional independent predictor. On the contrary total IgE levels are not affected by gestational age. Clinical limitations of total IgE is known but their determination can be useful to define atopy and to suggest follow-up of the children. PMID- 27562900 TI - Installation of multiple automated external defibrillators to prevent sudden death in school-aged children. AB - BACKGROUND: Recently, a student died of idiopathic ventricular fibrillation in a school where an automated external defibrillator (AED) had been installed. The tragedy could not be prevented because the only AED in the school was installed in the teachers' office, far from the school ground where the accident took place. This prompted establishment of a multiple AED system in schools. The aim of this study was to analyze the efficacy of the multiple AED system to prevent sudden death in school-aged children. METHODS: Assumed accident sites consisted of the school ground, gymnasium, Judo and Kendo hall, swimming pool, and classrooms on the first and the fourth floor. Multiple AED were installed in the teachers' office, gymnasium, some classrooms, and also provided as a portable AED in a rucksack. The time from the accident site to the teachers' office for single AED, and from the accident site to the nearest AED for multiple AED, was calculated. RESULTS: The AED retrieval time was significantly shorter in 55 elementary schools and in 29 junior high schools when multiple AED were installed compared with single AED. Except for the classroom on the fourth floor, the number of people who took >120 s to bring the AED to the accident site was lower when multiple AED were installed compared with the single AED. CONCLUSION: Multiple AED provided in appropriate sites can reduce the time to reach the casualty and hence prevent sudden death in school-aged children. PMID- 27562899 TI - Molecular and immunological characterization of cathepsin L-like cysteine protease of Paragonimus pseudoheterotremus. AB - Cathepsin L is a cysteine protease belonging to the papain family. In parasitic trematodes, cathepsin L plays essential roles in parasite survival and host parasite interactions. In this study, cathepsin L of the lung fluke Paragonimus pseudoheterotremus (PpsCatL) was identified and its molecular biological and immunological features characterized. A sequence analysis of PpsCatL showed that the gene encodes a 325-amino-acid protein that is most similar to P. westermani cathepsin L. The in silico three-dimensional structure suggests that PpsCatL is a pro-enzyme that becomes active when the propeptide is cleaved. A recombinant pro PpsCatL lacking the signal peptide (rPpsCatL), with a molecular weight of 35 kDa, was expressed in E. coli and reacted with P. pseudoheterotremus-infected rat sera. The native protein was detected in crude worm antigens and excretory secretory products and was localized in the cecum and in the lamellae along the intestinal tract of the adult parasite. Enzymatic activity of rPpsCatL showed that the protein could cleave the fluorogenic substrate Z-Phe-Arg-AMC after autocatalysis but was inhibited with E64. The immunodiagnostic potential of the recombinant protein was evaluated with an enzyme-linked immunosorbent assay (ELISA) and suggested that rPpsCatL can detect paragonimiasis with high sensitivity and specificity (100 and 95.6 %, respectively). This supports the further development of an rPpsCatL-ELISA as an immunodiagnostic tool. PMID- 27562901 TI - Bayesian inference for agreement measures. AB - The agreement of different measurement methods is an important issue in several disciplines like, for example, Medicine, Metrology, and Engineering. In this article, some agreement measures, common in the literature, were analyzed from a Bayesian point of view. Posterior inferences for such agreement measures were obtained based on well-known Bayesian inference procedures for the bivariate normal distribution. As a consequence, a general, simple, and effective method is presented, which does not require Markov Chain Monte Carlo methods and can be applied considering a great variety of prior distributions. Illustratively, the method was exemplified using five objective priors for the bivariate normal distribution. A tool for assessing the adequacy of the model is discussed. Results from a simulation study and an application to a real dataset are also reported. PMID- 27562902 TI - Intratonsillar abscess, a rare cause of odynophagia. PMID- 27562903 TI - Cervical vagus nerve neurilemmoma mimicking parathyroid adenoma. PMID- 27562904 TI - A Long-Term Follow-Up Investigation of Endobronchial Valves in Emphysema (the LIVE Study): Study Protocol and Six-Month Interim Analysis Results of a Prospective Five-Year Observational Study. AB - BACKGROUND: Randomized controlled trials indicate that significant lung volume reduction (ELVR) can be obtained with Zephyr(r) valves by occluding the target lobe in the absence of collateral ventilation, leading to relevant functional benefits in advanced emphysema patients. OBJECTIVES: To observe the long-term effects of endobronchial valve (EBV) implantation in emphysema patients screened by Chartis assessment in the context of daily pulmonology practice. METHODS: The LIVE Study is a prospective, observational, open-label, single-arm, multicenter trial conducted in Germany. 498 patients included in this interim analysis were enrolled between July 2, 2012, and September 16, 2014. The 6-month follow-up visit data were recorded for 343 patients (safety population), and complete data sets were available for 321 treated patients (efficacy population) - 56.4% male, age: 64.5 years, forced expiratory volume in 1 s (FEV1) % predicted: 31.3%, residual volume (RV) % predicted: 252%. RESULTS: Efficacy results at 6 months: FEV1 (l) increased by +100 ml (+11.9%), RV (l) decreased by -0.42 liter, and the COPD Assessment Test score decreased by -3.14 points (each p < 0.0001). Safety outcomes: A total of 66 adverse events (AEs; with 50 serious AEs - SAEs) were reported in 55 patients (16%) during the hospital stay for EBV placement - pneumothorax (35 cases), chronic obstructive pulmonary disease (COPD) exacerbation (5 cases), and pneumonia (4 cases). During the subsequent 6-month follow-up window, 170 SAEs were recorded in 125 patients (36.4%), predominantly COPD exacerbation (53% of the SAEs). CONCLUSION: The current results of this large-scale German observational study performed in the context of daily practice further demonstrates that ELVR with Zephyr(r) valves is an effective and well tolerated treatment option in advanced emphysema. PMID- 27562906 TI - Intraperitoneal lipomatosis: a rare clinicoradiological entity in a child. PMID- 27562905 TI - A Dyadic Behavioral Intervention to Optimize Same Sex Male Couples' Engagement Across the HIV Care Continuum: Development of and Protocol for an Innovative Couples-based Approach (Partner Steps). AB - BACKGROUND: An estimated one- to two-thirds of new human immunodeficiency virus (HIV) infections among US men who have sex with men (MSM) occur within the context of primary partnerships. Thus, HIV interventions that recognize and harness the power of relationships are needed. Increasingly, HIV prevention efforts are being directed toward improving engagement across the HIV care continuum from testing to linkage to care, antiretroviral therapy (ART) adherence, engagement in care, and viral suppression. However, to our knowledge, no behavioral interventions have attempted to address the HIV care continuum using a dyadic approach. OBJECTIVE: The objective of this paper is to describe the development of and protocol for an innovative couples-based approach to improving treatment adherence and engagement in care among HIV serodiscordant and concordant HIV-positive same sex male couples in the United States. METHODS: We developed the Partner Steps intervention by drawing from relationship-oriented theory, existing efficacious individual-level ART adherence interventions, couple focused HIV prevention interventions, and expert consultation. We incorporated new content to address all aspects of the HIV care continuum (eg, linkage to and retention in care) and to draw on relationship strengths through interactive activities. RESULTS: The resulting theory-based Partner Steps intervention is delivered by a trained bachelors-level counselor (interventionist) over 2 in person sessions with male-male dyads in which at least 1 partner has recent suboptimal engagement in HIV care. Each session is designed to use relationship strengths to increase motivation for HIV care and treatment, and cover sequential intervention "steps" relating to specific challenges in HIV care engagement and barriers to ART adherence. For each step, couples work with a trained interventionist to identify their unique challenges, actively problem-solve with the interventionist, and articulate and commit to working together to implement a plan in which each partner agrees to complete specific tasks. CONCLUSIONS: We drew on theory and evidence to develop novel intervention strategies that leverage strengths of relationships to address engagement across the entire HIV care continuum. We provide details on intervention development and content that may be of use to researchers as well as medical and mental health professionals for whom a dyadic approach to HIV prevention and care may best suit their patient population. PMID- 27562907 TI - Influence of tumor cell lines derived from different tissue on sonoporation efficiency under ultrasound microbubble treatment. AB - To reveal the effect of tumor cell lines derived from different tissue on sonoporation efficiency under ultrasound microbubble (USMB) treatment, and meanwhile to determine the optimum parameter combination for each tumor cell line. Human breast tumor (MCF-7), ovarian tumor (A2780), liver tumor (Bel7402) and thyroid tumor (ARO) were exposed to ultrasound in the presence of SonoVue MBs. The major parameters for the designed experiments including MB concentration (A1:10%, A2:20%, A3:30%), sound intensity (B1:0.5, B2:1.0, B3:1.5W/cm2), irradiation time (C1:30, C2:60, C3:90s). An orthogonal array experimental design based on three levels L9 (33) of the above three parameters was employed to optimize the sonoporation efficiency. MTT experiment was used to calculate cell survival rate. FD500 uptake assay and cytometry were performed to evaluate transference percentage. The optimum parameter combination for each tumor cell line was different (MCF-7: A3B1C1, A2780: A1B3C3, Bel7402: A2B3C2, ARO: A2B3C2). Under their own optimum parameter combination, four kinds of tumor cell line exhibited different optimum sonoporation efficiency (MCF-7: 55.05+/-5.29%; A2780: 45.62+/-7.35%; Bel7402: 39.37+/-4.11%; ARO: 53.37+/-3.94%). Multiple comparison with LSD-t test showed that the sonoporation efficiency between four kinds of cell line was statistically significant (P<0.05), with the exception of MCF-7 VS. ARO (P=0.487). Tumor cell lines derived from different tissue can impact the sonoporation efficiency, and optimizing the exposure parameters can safely and efficiently increase the cell membrane permeability. PMID- 27562908 TI - Degradation of 2,4-dichlorophenol using combined approach based on ultrasound, ozone and catalyst. AB - The present work investigates the application of ultrasound and ozone operated individually and in combination with catalyst (ZnO and CuO) for establishing the possible synergistic effects for the degradation of 2,4-dichlorophenol. The dependency of extent of degradation on the operating parameters like temperature (over the range of 30-36 degrees C), initial pH (3-9), catalyst as ZnO (loading of 0.025-0.15g/L) and CuO (loading of 0.02-0.1g/L) and initial concentration of 2,4-DCP (20-50ppm) has been established to maximize the efficacy of ultrasound (US) induced degradation. Using only US, the maximum degradation of 2,4-DCP obtained was 28.85% under optimized conditions of initial concentration as 20ppm, pH of 5 and temperature of 34 degrees C. Study of effect of ozone flow rate for approach of only ozone revealed that maximum degradation was obtained at 400mg/h ozone flow rate. The combined approaches such as US+O3, US+ZnO, US+CuO, O3+ZnO, O3+CuO, US+O3+ZnO and US+O3+CuO have been subsequently investigated under optimized conditions and observed to be more efficient as compared to individual approaches. The maximum extent of degradation for the combined operation of US+O3 (400mg/h)+ZnO (0.1g/L) and US+O3 (400mg/h)+CuO (0.08g/L) has been obtained as 95.66% and 97.03% respectively. The degradation products of 2,4-DCP have been identified using GC-MS analysis and the toxicity analysis has also been performed based on the anti-microbial activity test (agar-well diffusion method) for the different treatment strategies. The present work has conclusively established that the combined approach of US+O3+CuO was the most efficient treatment scheme resulting in near complete degradation of 2,4-DCP with production of less toxic intermediates. PMID- 27562909 TI - Synthesis and application of magnetic deep eutectic solvents: Novel solvents for ultrasound assisted liquid-liquid microextraction of thiophene. AB - Two novel magnetic deep eutectic solvents (MDESs), comprised of cheap and simple components named [choline chloride/phenol] [FeCl4] and [choline chloride/ethylene glycol] [FeCl4] were prepared and characterized by CHN elemental analysis, proton nuclear magnetic resonance (1H NMR), vibrating sample magnetometery (VSM), Raman, Fourier transform-infrared (FT-IR) and UV-Vis spectrometery. The extraction efficiency of the prepared MDESs has been investigated in ultrasound assisted liquid-liquid microextraction based MDES (UALLME-MDES). Briefly, MDESs were added to n-heptan containing thiophene. Then, MDESs were dispersed in n-heptane by sonication. After that, microdroplets of MDESs were collected by a magnet and the remained concentration of thiophene in n-heptane phase was analyzed by GC-FID. The results indicated that [choline chloride/phenol] [FeCl4] has higher extraction efficiency than [choline chloride/ethylene glycol] [FeCl4]. This work opens a new way to the application of MDESs. PMID- 27562910 TI - Repeatedly using the decomposition product of struvite by ultrasound stripping to remove ammonia nitrogen from landfill leachate. AB - In this study, the decomposition of struvite by ultrasound stripping and the recycle use of the decomposition product for the treatment of landfill leachate were investigated. The results indicated that when the decomposition of struvite by ultrasound stripping was performed at 55 degrees C for 40min, the ammonium in the struvite could be almost completely eliminated from the solution system. The characterization analysis showed that magnesium phosphate and the dissolved phosphate ions were the main active derivatives. Approximately 90% of the total ammonia nitrogen (TAN) in landfill leachate can be removed by reusing the decomposition product at pH 9 for 60min. Repeated use of the struvite decomposition product revealed that the TAN removal efficiency decreased with an increase in the number of recycles. However, in the process of multiple recycling, about 90% of TAN removal could be maintained by supplementing a certain amount of the preformed struvite to the solution for every recycle. An economic analysis demonstrated that 79.3% of the treatment cost could be saved by the proposed process compared to the non-recycling process. PMID- 27562911 TI - Selection of red deer spermatozoa with different cryoresistance using density gradients. AB - The objective of sperm selection media is selecting the best spermatozoa and to remove seminal plasma and diluent for using them in assisted reproductive techniques. It is known that individuals show different cryoresistance in response to the same freezing procedure. Our hypothesis was that the efficacy of selection media could be dissimilar for samples with different sperm quality after thawing. Epididymal sperm samples from mature Iberian red deer were collected and frozen. Males were classified as with high post-thaw sperm quality when sperm motility (SM) >= 70%, or as with low post-thaw sperm quality when SM <= 69%. Samples were centrifuged using the following density gradients (DG): Percoll(r) , Puresperm(r) and BovipureTM , and several functional sperm parameters were assessed after sperm selecting and washing. Males classified with high sperm quality had higher post-thawing values (p > .05) for all parameters evaluated, except for linearity index, than those categorized as low sperm quality. After selection, some sperm characteristics improved (viability, apoptosis and mitochondrial activity) for both groups, showing the males with high sperm quality higher values in all sperm parameters except for kinematic traits and DNA fragmentation index (%DFI), regardless of DG. BovipureTM yield lower values of sperm motility, viability, apoptosis and mitochondrial activity in relation to Percoll(r) and Puresperm(r) considering both quality groups. There was an interaction between the type of DG and sperm quality group for sperm viability (p = .040) and apoptosis (p = .003). Thus, Percoll(r) selected less live and more apoptotic spermatozoa than Puresperm(r) and BovipureTM for males with low sperm quality. In conclusion, the DG are more efficient selecting spermatozoa from samples with high sperm quality, acting differently depending on initial sperm quality. PMID- 27562912 TI - Post-traumatic stress symptoms in Swedish obstetricians and midwives after severe obstetric events: a cross-sectional retrospective survey. AB - OBJECTIVE: To examine post-traumatic stress reactions among obstetricians and midwives, experiences of support and professional consequences after severe events in the labour ward. DESIGN: Cross-sectional online survey from January 7 to March 10, 2014. POPULATION: Members of the Swedish Society of Obstetrics and Gynaecology and the Swedish Association of Midwives. METHODS: Potentially traumatic events were defined as: the child died or was severely injured during delivery; maternal near-miss; maternal mortality; and other events such as violence or threat. The validated Screen Questionnaire Posttraumatic Stress Disorder (SQ-PTSD), based on DSM-IV (1994) 4th edition, was used to assess partial post-traumatic stress disorder (PTSD) and probable PTSD. MAIN OUTCOME MEASURES: Partial or probable PTSD. RESULTS: The response rate was 47% for obstetricians (n = 706) and 40% (n = 1459) for midwives. Eighty-four percent of the obstetricians and 71% of the midwives reported experiencing at least one severe event on the delivery ward. Fifteen percent of both professions reported symptoms indicative of partial PTSD, whereas 7% of the obstetricians and 5% of the midwives indicated symptoms fulfilling PTSD criteria. Having experienced emotions of guilt or perceived insufficient support from friends predicted a higher risk of suffering from partial or probable PTSD. Obstetricians and midwives with partial PTSD symptoms chose to change their work to outpatient care significantly more often than colleagues without these symptoms. CONCLUSIONS: A substantial proportion of obstetricians and midwives reported symptoms of partial or probable PTSD after severe traumatic events experienced on the labour ward. Support and resilience training could avoid suffering and consequences for professional carers. TWEETABLE ABSTRACT: In a survey 15% of Swedish obstetricians and midwives reported PTSD symptoms after their worst obstetric event. PMID- 27562913 TI - Measuring the effects of structural turnout suits on firefighter range of motion and comfort. AB - Range of motion (ROM) can be restricted by wearing stiff and bulky clothing. This is particularly true of firefighter suits that are constructed using fabric layers to provide thermal protection from fire. This study developed an evaluation technique to quantify the loss of mobility associated with wearing firefighters' protective suits that were deliberately selected to represent similar ergonomic design features. The ROM of 10 firefighters was measured using electro-goniometers attached to their bodies while they wore uniforms and a reference outfit, and performed specific movements. The most restrictive uniform is the Bulky suit that contained additional layers of materials in sleeves and on the knees. The Traditional Suit was more ROM restrictive than Ergonomic. The subjective evaluation of suits supported the objective assessments provided by the electro-goniometers. A 3-D body scanning technique was employed to establish a correlation between the bulkiness of firefighter outfits and subject ROM. Practitioner Summary: This study presents a methodology for measurements of range of motion (ROM) in firefighters wearing personal protective equipment (PPE). Even small differences in designs of PPE may impact firefighters' ROM, which can be detected by electro-goniometers providing measurements if they are attached along the joint to measure limb angular movement. PMID- 27562915 TI - Hypoxia-Inducible Factor-1alpha in Smooth Muscle Cells Protects Against Aortic Aneurysms-Brief Report. AB - OBJECTIVE: The purpose of this study was to determine the role of smooth muscle cell-derived hypoxia-inducible factor-1alpha (Hif-1alpha) in the pathogenesis of aortic aneurysms. APPROACH AND RESULTS: Control mice and smooth muscle cell specific hypoxia-inducible factor-1alpha-deficient mice were infused with beta aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. Mutant mice experienced increased levels of aneurysm formation of the thoracic or abdominal aorta with more severe elastin disruption, compared with control mice. Smooth muscle cell-specific hypoxia-inducible factor 1alpha deficiency did not affect matrix metalloproteinase-2 activity; however, the activity of lysyl oxidase and the levels of tropoelastin mRNA in the angiotensin II- and beta-aminopropionitrile-treated aortae, associated with elastin fiber formation, were suppressed. Furthermore, we observed reduced volumes of mature cross-linked elastin in the thoracoabdominal aorta after treatment with angiotensin II and beta-aminopropionitrile. CONCLUSIONS: Deficiency of smooth muscle cell-derived hypoxia-inducible factor-1alpha augments aortic aneurysms, accompanied by disruption of elastin fiber formation, but not changes of elastin fiber degradation. PMID- 27562914 TI - Delta-Like Ligand 4-Notch Signaling in Macrophage Activation. AB - The Notch signaling pathway regulates the development of various cell types and organs, and also contributes to disease mechanisms in adults. Accumulating evidence suggests its role in cardiovascular and metabolic diseases. Notch signaling components also control the phenotype of immune cells. Delta-like ligand 4 (Dll4) of the Notch pathway promotes proinflammatory activation of macrophages in vitro and in vivo. Dll4 blockade attenuates chronic atherosclerosis, vein graft disease, vascular calcification, insulin resistance, and fatty liver in mice. The Dll4-Notch axis may, thus, participate in the shared mechanisms for cardiometabolic disorders, serving as a potential therapeutic target for ameliorating these global health problems. PMID- 27562916 TI - GLP-1-Based Therapies Have No Microvascular Effects in Type 2 Diabetes Mellitus: An Acute and 12-Week Randomized, Double-Blind, Placebo-Controlled Trial. AB - OBJECTIVE: To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus. APPROACH AND RESULTS: We studied 57 patients with type 2 diabetes mellitus (mean+/-SD age: 62.8+/-6.9 years; body mass index: 31.8+/-4.1 kg/m(2); HbA1c [glycated hemoglobin] 7.3+/-0.6%) in an acute and 12-week randomized, placebo-controlled, double-blind trial conducted at the Diabetes Center of the VU University Medical Center. In the acute study, the GLP-1 receptor agonist exenatide (therapeutic concentrations) or placebo (saline 0.9%) was administered intravenously. During the 12-week study, patients received the GLP-1 receptor agonist liraglutide (1.8 mg daily), the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg daily), or matching placebos. Capillary perfusion was assessed by nailfold skin capillary videomicroscopy and vasomotion by laser Doppler fluxmetry, in the fasting state and after a high-fat mixed meal. In neither study, treatment affected fasting or postprandial capillary perfusion compared with placebo (P>0.05). In the fasting state, acute exenatide infusion increased neurogenic vasomotion domain power, while reducing myogenic domain power (both P<0.05). After the meal, exenatide increased endothelial domain power (P<0.05). In the 12-week study, no effects on vasomotion were observed. CONCLUSIONS: Despite modest changes in vasomotion, suggestive of sympathetic nervous system activation and improved endothelial function, acute exenatide infusion does not affect skin capillary perfusion in type 2 diabetes mellitus. Twelve-week treatment with liraglutide or sitagliptin has no effect on capillary perfusion or vasomotion in these patients. Our data suggest that the effects of GLP-1-based therapies on glucose are not mediated through microvascular responses. PMID- 27562917 TI - Autotaxin-Lysophosphatidic Acid Axis Acts Downstream of Apoprotein B Lipoproteins in Endothelial Cells. AB - OBJECTIVE: As they travel through the blood stream, plasma lipoproteins interact continuously with endothelial cells (ECs). Although the focus of research has mostly been guided by the importance of lipoproteins as risk factors for atherosclerosis, thrombosis, and other cardiovascular diseases, little is known about the mechanisms linking lipoproteins and angiogenesis under physiological conditions, and particularly, during embryonic development. In this work, we performed global mRNA expression profiling of endothelial cells from hypo-, and hyperlipidemic zebrafish embryos with the goal of uncovering novel mediators of lipoprotein signaling in the endothelium. APPROACH AND RESULTS: Microarray analysis was conducted on fluorescence-activated cell sorting-isolated fli1:EGFP(+) ECs from normal, hypo-, and hyperlipidemic zebrafish embryos. We found that opposed levels of apoprotein B lipoproteins result in differential expression of the secreted enzyme autotaxin in ECs, which in turn affects EC sprouting and angiogenesis. We further demonstrate that the effects of autotaxin in vivo are mediated by lysophosphatidic acid (LPA)-a well-known autotaxin activity product-and that LPA and LPA receptors participate as well in the response of ECs to lipoprotein levels. CONCLUSIONS: Our findings provide the first in vivo gene expression profiling of ECs facing different levels of plasma apoprotein B lipoproteins and uncover a novel lipoprotein-autotaxin-LPA axis as regulator of EC behavior. These results highlight new roles for lipoproteins as signaling molecules, which are independent of their canonical function as cholesterol transporters. PMID- 27562918 TI - Tularemia Masquerading as Ecthyma. PMID- 27562919 TI - Reply. PMID- 27562920 TI - Multiplex polymerase chain reaction testing in pediatric inpatients with febrile seizures. PMID- 27562922 TI - Guest Editorial. PMID- 27562921 TI - Diagnostic Testing and Hospital Outcomes of Children with Neurologic Impairment and Bacterial Pneumonia. AB - OBJECTIVE: To assess hospital-level variability in diagnostic testing and outcomes for children with neurologic impairment hospitalized with pneumonia. STUDY DESIGN: A retrospective cohort study of 27 455 children ages 1-18 years with neurologic impairment hospitalized with pneumonia at 39 children's hospitals. K-means clustering was used to assign each hospital to 1 of 3 groups (termed A, B, and C) based on similar diagnostic testing patterns. Outcomes of hospital-level median length of stay (LOS), 30-day readmissions, and pneumonia associated complications were compared while controlling for patient differences. RESULTS: Overall, 48.5% had comorbid complex chronic conditions, and 25.4% were assisted with medical technology. Outcomes and diagnostic testing varied across hospitals: median hospital-level LOS, 3.2 days (IQR 2.8-3.8); median readmission, 8.4% (IQR 6.8,-10.0); and median pneumonia-associated complication rate, 23.1% (IQR 18.7-26.8). Despite similar populations, hospitals in group A tended to perform fewer tests than those in groups B and C. Across hospital groups, there was a significant difference in adjusted readmission rates (group A 7.2%, group B 9.0%, group C 7.7%, P = .003). There was no significant difference in adjusted median LOS (group A 3.4 days, group B 3.2 days, group C 3.3 days, P = .3) or adjusted pneumonia-associated complication rates (group A 22.5%, group B 22.5%, group C 25.0%, P = .6). CONCLUSIONS: For children with neurologic impairment hospitalized with pneumonia, across hospital differences in diagnostic testing were not associated with clinically meaningful differences in outcomes. High utilizing hospitals may be able to decrease diagnostic testing for children with neurologic impairment hospitalized with pneumonia without adversely impacting outcomes. PMID- 27562923 TI - Hypotrophic muscle ipsilateral to the bending side is not a therapeutic target in recurrent and alternating lateral trunk flexion in Parkinson disease: Case report. PMID- 27562924 TI - Modularity in network neuroscience and neural reuse. AB - Neural reuse allegedly stands in stark contrast against a modular view of the brain. However, the development of unique modularity algorithms in network science has provided the means to identify functionally cooperating, specialized subsystems in a way that remains consistent with the neural reuse view and offers a set of rigorous tools to fully engage in Anderson's (2014) research program. PMID- 27562926 TI - Human cooperation shows the distinctive signatures of adaptations to small-scale social life. AB - The properties of individual carbon atoms allow them to chain into complex molecules of immense length. They are not limited to structures involving only a few atoms. The design features of our evolved neural adaptations appear similarly extensible. Individuals with forager brains can link themselves together into unprecedentedly large cooperative structures without the need for large group beneficial modifications to evolved human design. Roles need only be intelligible to our social program logic, and judged better than alternatives. PMID- 27562925 TI - Chemotherapy for post-myelofibrosis acute myeloid leukemia: eradication of the leukemic clone but not the MPN clone. PMID- 27562927 TI - Laying the foundation for evonomics. AB - The target article is a major step toward integrating the biological and human related sciences. It is highly relevant to economics and public policy formulation in the real world, in addition to its basic scientific import. My commentary covers a number of points, including avoiding an excessively narrow focus on agriculture, the importance of multilevel selection and complex systems theory, and utopic versus dystopic scenarios for the future. PMID- 27562928 TI - Nutritional risk screening 2002 should be used in hospitalized patients with chronic obstructive pulmonary disease with respiratory failure to determine prognosis: A validation on a large Chinese cohort. PMID- 27562930 TI - Validation of hospital discharge diagnoses for hypertensive disorders of pregnancy. AB - INTRODUCTION: A correct diagnosis of preeclampsia and gestational hypertension is important for treatment and epidemiological studies. Changes in diagnostic criteria and underreporting in certain subsets of patients may hamper validity of the diagnoses. MATERIALS AND METHODS: We validated the discharge diagnoses of preeclampsia and gestational hypertension, which are reported to the Danish National Patient Registry, in a cohort of 2163 pregnant women by retrospective evaluation of electronic hospital data. RESULTS: A preeclampsia discharge diagnosis was found in 113 (5.2%) of the participants. After validation, significantly more patients fulfilled criteria for diagnosis of preeclampsia (n = 163, 7.5%, p = 0.002); more had severe preeclampsia, 14 (0.6%) vs. 70 (3.2%), p < 0.001 and gestational hypertension, 62 (2.9%) vs. 46 (2.1%), p = 0.12. The diagnostic sensitivity for preeclampsia by discharge diagnosis was 55.8%; severe preeclampsia 18.6%; gestational hypertension 39.1%. Corresponding positive predictive values were 80.5, 92.9 and 29.0%. Misclassification occurred in 4.3, 2.7 and 3.3%, respectively. Misclassification was more prevalent in obese compared to lean women (10% vs. 3.6%, p < 0.0001). CONCLUSIONS: Discharge diagnoses substantially underestimated the prevalence of preeclampsia, especially severe preeclampsia. Misclassification was most common in obese preeclamptic women. These findings depict the limitations associated with the direct use of discharge diagnoses of hypertensive disorders in pregnancy for research purposes. PMID- 27562929 TI - Evaluation of titanium dioxide nanocrystal-induced genotoxicity by the cytokinesis-block micronucleus assay and the Drosophila wing spot test. AB - Titanium dioxide nanocrystals (TiO2 NCs) crystalline structures include anatase, rutile and brookite. This study evaluated the genotoxic effects of 3.4 and 6.2 nm anatase TiO2 NCs and 78.0 nm predominantly rutile TiO2 NCs through an in vitro micronucleus (MN) assay using V79 cells and an in vivo somatic mutation and recombination test in Drosophila wings. The MN assay was performed with nontoxic concentrations of TiO2 NCs. Only anatase (3.4 nm) at the highest concentration (120 MUM) induced genotoxicity in V79 cells. In the in vivo test, Drosophila melanogaster larvae obtained from standard (ST) or high bioactivation (HB) crosses were treated with TiO2 NCs. In the ST cross, no mutagenic effects were observed. However, in the HB cross, TiO2 NCs (3.4 nm) were mutagenic at 1.5625 and 3.125 mM, while 78.0 nm NCs increased mutant spots at all concentrations tested except 3.125 mM. Only the smallest anatase TiO2 NCs induced mutagenic effects in vitro and in vivo. For rutile TiO2 NCs, no clastogenic/aneugenic effects were observed in the MN assay. However, they were mutagenic in Drosophila. Therefore, both anatase and rutile TiO2 NCs induced mutagenicity. Further research is necessary to clarify the TiO2 NCs genotoxic/mutagenic action mechanisms. PMID- 27562931 TI - First human case of tick-borne encephalitis virus infection acquired in the Netherlands, July 2016. AB - In July 2016, the first autochthonous case of tick-borne encephalitis was diagnosed in the Netherlands, five days after a report that tick-borne encephalitis virus (TBEV) had been found in Dutch ticks. A person in their 60s without recent travel history suffered from neurological symptoms after a tick bite. TBEV serology was positive and the tick was positive in TBEV qRT-PCR. TBEV infection should be considered in patients with compatible symptoms in the Netherlands. PMID- 27562933 TI - Recommended screening and preventive evaluation practices of adult candidates for hematopoietic stem cell transplantation. AB - INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is associated with a substantial risk of morbidity and mortality. Better selection of HSCT patients for intensive treatment, and consequently reduction of non-beneficial care, may improve the therapeutic outcome. AREAS COVERED: This manuscript provides a systematic review which examines t he current criteria for selection of HSCT patients. EXPERT OPINION: Identifying patients who may benefit from HSCT involves many factors, including overall health, prior therapies, age, disease, and stage. The decision regarding transplant eligibility should be made on a case by case basis, based on a risk-benefit assessment. The advent of the comorbidity index as a measure of health status at the time of HSCT has facilitated the incorporation of comorbidities into the pre-transplant assessment of patients. Many HSCT protocols are still age-dependent, with criteria limited to patients either younger or older than arbitrary age cut-offs.The prognostic role of age in the transplant setting has never been consistent. As physicians and researchers continue improving the HSCT process and outcomes, optimization of the delivery of a comprehensive treatment plan should become an important component of overall patient management. PMID- 27562932 TI - The opposing roles of laminin-binding integrins in cancer. AB - Integrins play an important role in cell adhesion by linking the cytoskeleton of cells to components in the extracellular matrix. In this capacity, integrins cooperate with different cell surface receptors, including growth factor receptors and G-protein coupled receptors, to regulate intracellular signaling pathways that control cell polarization, spreading, migration, survival, and gene expression. A distinct subfamily of molecules in the integrin family of adhesion receptors is formed by receptors that mediate cell adhesion to laminins, major components of the basement membrane that lie under clusters of cells or surround them, separating them from other cells and/or adjacent connective tissue. During the past decades, many studies have provided evidence for a role of laminin binding integrins in tumorigenesis, and both tumor-promoting and suppressive activities have been identified. In this review we discuss the dual role of the laminin-binding integrins alpha3beta1 and alpha6beta4 in tumor development and progression, and examine the factors and mechanisms involved in these opposing effects. PMID- 27562934 TI - Urine Cytology: Collection, Film Preparation, and Evaluation. AB - Cytologic examination of the urine sediment in animals suspected of having urinary tract disease or lower urinary tract masses is one of the best means of distinguishing inflammation, infection, and neoplasia and can help determine if a positive dipstick result for hemoglobin/blood is due to hemorrhage or blood contamination. The quality of the specimen collection and handling plays an important role in the quality of results, the validity of interpretations, and selection of appropriate course of action. The method of sample collection aids localization of pathology. Air dry but do not heat fix, freeze, or expose films to formalin fumes, temperature extremes, or condensation. PMID- 27562937 TI - Pseudoinvasion appearing as a deeply invasive malignant colorectal polyp. PMID- 27562938 TI - Safety and feasibility of an endoluminal-suturing device for endoscopic gastric reduction (with video). AB - BACKGROUND AND AIMS: Obesity is a major pandemic disease. Surgical therapy is highly effective, but its availability will likely be overwhelmed by the burden of the disease. Endoscopic technologies that could reproduce some of the clinical effects of surgery may become part of the treatment armamentarium. A simple transoral restrictive procedure could play a role in first-line surgical management. METHODS: We evaluated the safety and feasibility of transmural suturing using a simple triangulation platform for gastric volume reduction through the creation of multiple double plicatures. RESULTS: Between May and July 2015, 11 obese (body mass index 34.6 +/- 2.1 kg/m2) patients (mean age, 36 +/- 10 years) underwent gastroplasty through transmural endoscopic sutures (performed using a triangulation platform and an endoscopic stitcher). The median duration of the procedure was 2.00 hours (range, 1.15-3.15 hours) and dramatically decreased after the first 5 cases. No severe adverse events were observed. Mean (standard deviation) weight loss and percentage of excess weight loss were 5.8 kg (2.7%) and 21% (9%) at 1 month (n = 11), 8.8 kg (4.9%) and 33% (22%) at 3 months (n = 10), and 10.9 kg (7.3%) and 41% (33%) at 6 months (n = 10). CONCLUSIONS: Transoral endoscopic gastroplasty performed using a simple triangulation platform and a dedicated suturing device appears to be safe and effective at mid-term follow-up in creating gastric restriction and inducing weight loss in this first in-humans experience. (Clinical trials registration number: NCT02534662.). PMID- 27562939 TI - Clinical utility of rapid on-site cytopathology. PMID- 27562940 TI - Asymmetric Alternating Copolymerization of Meso-epoxides and Cyclic Anhydrides: Efficient Access to Enantiopure Polyesters. AB - Synthesis of stereoregular polyesters with main-chain chirality was achieved for the first time by the asymmetric copolymerization of meso-epoxides and cyclic anhydrides using catalyst systems based on enantiopure bimetallic complexes. The combination of the biphenol-linked dinuclear aluminum complex with tert-butyl groups in the phenolate ortho-positions and a nucleophilic co-catalyst was found to be more efficient in catalyzing this asymmetric copolymerization, affording enantiomerically enriched polyesters (up to 91% ee) with completely alternating structure and narrow molecular weight distribution. It was discovered that the isotactic-enriched poly(cyclopentene phthalate) is a typical semicrystalline material with a melting endothermic peak at 221 degrees C. This study is expected to provide a promising route to prepare various stereoregular polyesters having a wide variety of physical properties and degradability. PMID- 27562941 TI - Predictive Factors for Verbal Memory Performance Over Decades of Aging: Data from the Women's Healthy Ageing Project. AB - BACKGROUND: Abnormalities in brain structure and function can occur several decades prior to the onset of cognitive decline. It is in the preceding decades that an intervention is most likely to be effective, when informed by an understanding of factors contributing to the disease prodrome. Few studies, however, have sufficient longitudinal data on relevant risks to determine the optimum targets for interventions to improve cognition in aging. In this article we examine the timing and exposure of factors contributing to verbal memory performance in later life. METHODS: 387 participants from the population-based Women's Healthy Ageing Project, mean age at baseline of 49.6 years (range: 45-55 years), had complete neuropsychiatric assessments, clinical information, physical measures, and biomarkers collected at baseline, with at least three follow-up visits that included at least one cognitive reassessment. Mixed linear models were conducted to assess the significance of risk factors on later-life verbal memory. We explored the influence of early, contemporaneous, and cumulative exposures. RESULTS: Younger age and better education were associated with baseline memory test performance (CERAD). Over the 20 years of study follow-up, cumulative mid- to late-life physical activity had the strongest effect on better later life verbal memory (0.136 [0.058, 0.214]). The next most likely contributors to verbal memory in late life were the negative effect of cumulative hypertension (-0.033 [-0.047, -0.0.18] and the beneficial effect of HDL cholesterol (0.818 [0.042, 1.593]). CONCLUSIONS: Findings suggest that midlife interventions focused on physical activity, hypertension control, and achieving optimal levels of HDL cholesterol will help maintain later-life verbal memory skills. PMID- 27562942 TI - A Window of MHM Demethylation Correlates with Key Events in Gonadal Differentiation in the Chicken. AB - The MHM (male hypermethylated) region on the chicken Z chromosome is of interest in terms of sex determination both because hypermethylation of the promoter in males results in female-specific expression, and in females the non-coding transcripts accumulate in the region of a locus that encodes a key candidate gene for testis differentiation in birds - DMRT1. However, it has yet to be established whether MHM plays a role in either sex determination or gonadal development in chicken. Here, we sought to establish the MHM methylation pattern during chicken gonadal development and determine how this pattern correlates with the expression profiles of genes involved in sex determination and gonadal differentiation. As expected, we found that MHM methylation levels were higher in male than in female gonads at most stages of development. We also showed that there was no significant difference in the methylation patterns between the right and left gonad and that the pattern of methylation in female gonads was not affected by sex reversal. However, we did find an unexpected window where MHM promoter methylation levels were very low in both males and females. This developmental window coincided with a stage of gonad development where there is a dramatic increase in expression of key testis genes in males and of key ovary genes in females. The current study raises the possibility that the non-coding RNA transcripts of MHM may affect testis and ovary differentiation by influencing sex-specific gene expression. PMID- 27562943 TI - Waste production and regional growth of marine activities an econometric model. AB - Coastal regions are characterized by intense human activity and climatic pressures, often intensified by competing interests in the use of marine waters. To assess the effect of public spending on the regional economy, an econometric model is here proposed. Not only are the regional investment and the climatic risks included in the model, but also variables related to the anthropogenic pressure, such as population, economic activities and waste production. Feedback effects of economic and demographic expansion on the pollution of coastal areas are also considered. It is found that dangerous waste increases with growing shipping and transportation activities and with growing population density in non touristic coastal areas. On the other hand, the amount of non-dangerous wastes increases with marine mining, defense and offshore energy production activities. However, lower waste production occurs in areas where aquaculture and touristic industry are more exploited, and accompanied by increasing regional investment in waste disposal. PMID- 27562945 TI - Corrigendum. PMID- 27562944 TI - Left Ventricular Mechanics in Patients with Abnormal Origin of the Left Main Coronary Artery from the Pulmonary Trunk Late after Successful Repair. AB - OBJECTIVE: Our aim was to evaluate left ventricular (LV) mechanics by using speckle tracking echocardiography (STE) in asymptomatic patients with abnormal origin of the left main coronary artery from the pulmonary trunk (ALCAPA), late after successful repair, in the presence of LV ejection fraction (EF) >50%. METHODS: We studied 30 ALCAPA patients (median age 4 years, range 1-25 years, NYHA class I, LVEF >50%) and 16 healthy age- and sex-matched controls (median age 5 years, range 1-25 years). All underwent standard echocardiographic evaluation and STE. RESULTS: LV dimensions and LVEF (63.6 +/- 8.2% vs. 64.1 +/- 5.1%, p = 0.826) were not different between patients and controls. Diastolic parameters were significantly abnormal in our patients versus controls (E/e' average: 11.9 +/- 5.8 vs. 6.6 +/- 3.0, p = 0.0014). Global LV longitudinal strain was significantly lower in ALCAPA patients versus controls (-17.6 +/- 3.5% vs. -23.4 +/- 3.1%, p < 0.0001). LV torsion (9.1 +/- 4.9 degrees vs. 11.9 +/- 3.3 degrees , p = 0.046) was significantly impaired in ALCAPA patients. CONCLUSIONS: After successful repair in asymptomatic ALCAPA patients, despite an LVEF >50%, diastolic function, LV longitudinal deformation and LV torsion remain impaired. We suggest including a detailed study of the diastolic function and cardiac mechanics in the clinical follow-up of these patients to identify the subgroup of patients at higher risk. PMID- 27562946 TI - KIDS SAVE LIVES implementation in Europe: A survey through the ERC Research NET. PMID- 27562947 TI - Is investing on social networks a winning strategy to promote cardiopulmonary resuscitation guidelines? A supportive example from Italy. PMID- 27562948 TI - Augmented survival of out-of-hospital cardiac arrest victims with the use of mobile phones for emergency communication under the DA-CPR protocol getting information from callers beside the victim. AB - PURPOSE: To investigate the impacts of emergency calls made using mobile phones on the quality of dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) and survival from out-of-hospital cardiac arrests (OHCAs) that were not witnessed by emergency medical service (EMS). METHODS: In this prospective study, we collected data for 2530 DA-CPR-attempted medical emergency cases (517 using mobile phones and 2013 using landline phones) and 2980 non-EMS-witnessed OHCAs (600 using mobile phones and 2380 using landline phones). Time factors and quality of DA CPR, backgrounds of callers and outcomes of OHCAs were compared between mobile and landline phone groups. RESULTS: Emergency calls are much more frequently placed beside the arrest victim in mobile phone group (52.7% vs. 17.2%). The positive predictive value and acceptance rate of DA-CPR in mobile phone group (84.7% and 80.6%, respectively) were significantly higher than those in landline group (79.2% and 70.9%). The proportion of good-quality bystander CPR in mobile phone group was significantly higher than that in landline group (53.5% vs. 45.0%). When analysed for all non-EMS-witnessed OHCAs, rates of 1-month survival and 1-year neurologically favourable survival in mobile phone group (7.8% and 3.5%, respectively) were higher than those in landline phone group (4.6% and 1.9%; p<0.05). Multiple logistic regression analysis, including other backgrounds, revealed that mobile phone calls were associated with increased 1 month survival in the subgroup of OHCAs receiving bystander CPR (adjusted odds ratio, 1.84; 95% CI, 1.15-2.92). CONCLUSION: Emergency calls made using mobile phones are likely to augment the survival from OHCAs by improving DA-CPR. PMID- 27562949 TI - Barriers to Care in Elderly Chinese Adults with Heart Disease. PMID- 27562951 TI - Therapeutic applications of CRISPR RNA-guided genome editing. AB - The rapid development of programmable nuclease-based genome editing technologies has enabled targeted gene disruption and correction both in vitro and in vivo This revolution opens up the possibility of precise genome editing at target genomic sites to modulate gene function in animals and plants. Among several programmable nucleases, the type II clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated nuclease 9 (Cas9) system has progressed remarkably in recent years, leading to its widespread use in research, medicine and biotechnology. In particular, CRISPR-Cas9 shows highly efficient gene editing activity for therapeutic purposes in systems ranging from patient stem cells to animal models. However, the development of therapeutic approaches and delivery methods remains a great challenge for biomedical applications. Herein, we review therapeutic applications that use the CRISPR-Cas9 system and discuss the possibilities and challenges ahead. PMID- 27562950 TI - The health and economic burden of bloodstream infections caused by antimicrobial susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study. AB - We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34 2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13 2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae. PMID- 27562952 TI - Mouse models for pre-clinical drug testing in leukemia. AB - INTRODUCTION: The development of novel drugs which specifically target leukemic cells, with the overall aim to increase complete remission and to reduce toxicity and morbidity, is the most important prerequisite for modern leukemia treatment. In this regard, the current transition rate of potential novel drugs from bench to bedside is remarkably low. Although many novel drugs show promising data in vitro and in vivo, testing of these medications in clinical phase I trials is often sobering with intolerable toxic side effects leading to failure in FDA approval. Areas covered: In this review, the authors discuss the development of murine model generation in the context of targeted therapy development for the treatment of childhood leukemia, aiming to decrease the attrition rate of progressively complex targeted therapies ranging from small molecules to cell therapy. As more complex therapeutic approaches develop, more complex murine models are needed, to recapitulate closely the human phenotype. Expert opinion: Combining xenograft models for efficacy testing and GEMMs for toxicity testing will be a global approach for pre-clinical testing of complex therapeutics and will contribute to the clinical approval of novel compounds. Finally, this approach is likely to increase clinical approval of novel compounds. PMID- 27562953 TI - Effect of Playing Kick Shuttlecock on the Estrogen Levels, Bone Mineral Density, and Postural Balance of Postmenopausal Women. PMID- 27562954 TI - The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia. AB - Body temperature homeostasis is critical for survival and requires precise regulation by the nervous system. The hypothalamus serves as the principal thermostat that detects and regulates internal temperature. We demonstrate that the ion channel TRPM2 [of the transient receptor potential (TRP) channel family] is a temperature sensor in a subpopulation of hypothalamic neurons. TRPM2 limits the fever response and may detect increased temperatures to prevent overheating. Furthermore, chemogenetic activation and inhibition of hypothalamic TRPM2 expressing neurons in vivo decreased and increased body temperature, respectively. Such manipulation may allow analysis of the beneficial effects of altered body temperature on diverse disease states. Identification of a functional role for TRP channels in monitoring internal body temperature should promote further analysis of molecular mechanisms governing thermoregulation and foster the genetic dissection of hypothalamic circuits involved with temperature homeostasis. PMID- 27562955 TI - Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. AB - The activated spliceosome (Bact) is in a catalytically inactive state and is remodeled into a catalytically active machine by the RNA helicase Prp2, but the mechanism is unclear. Here, we describe a 3D electron cryomicroscopy structure of the Saccharomyces cerevisiae Bact complex at 5.8-angstrom resolution. Our model reveals that in Bact, the catalytic U2/U6 RNA-Prp8 ribonucleoprotein core is already established, and the 5' splice site (ss) is oriented for step 1 catalysis but occluded by protein. The first-step nucleophile-the branchsite adenosine-is sequestered within the Hsh155 HEAT domain and is held 50 angstroms away from the 5'ss. Our structure suggests that Prp2 adenosine triphosphatase-mediated remodeling leads to conformational changes in Hsh155's HEAT domain that liberate the first-step reactants for catalysis. PMID- 27562957 TI - Tensions of refugee politics in Europe. PMID- 27562956 TI - Replication of human noroviruses in stem cell-derived human enteroids. AB - The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack of a robust and reproducible in vitro cultivation system. HuNoVs are the leading cause of gastroenteritis worldwide. We report the successful cultivation of multiple HuNoV strains in enterocytes in stem cell-derived, nontransformed human intestinal enteroid monolayer cultures. Bile, a critical factor of the intestinal milieu, is required for strain-dependent HuNoV replication. Lack of appropriate histoblood group antigen expression in intestinal cells restricts virus replication, and infectivity is abrogated by inactivation (e.g., irradiation, heating) and serum neutralization. This culture system recapitulates the human intestinal epithelium, permits human host-pathogen studies of previously noncultivatable pathogens, and allows the assessment of methods to prevent and treat HuNoV infections. PMID- 27562958 TI - Estimating true hospital morbidity of complications associated with mumps outbreak, England, 2004/05. AB - Mumps outbreaks in highly vaccinated populations continue to be reported globally. Therefore, quantifying the burden of mumps morbidity accurately will be necessary to better assess the impact of mumps vaccination programmes. We aim to estimate the true morbidity resulting from mumps complications in terms of hospitalised orchitis, meningitis, oophoritis and pancreatitis in England during the outbreak in 2004/05. This outbreak in England led to a clear increase in hospitalisations coded to mumps for complications of orchitis in those born in the 1970s and 1980s and possibly for meningitis in those born in the 1980s. A simple statistical model, based on analysing time trends for diagnosed complications in hospital databases with routine laboratory surveillance data, found that the actual morbidity was much higher. There were 2.5 times (166 cases) more mumps orchitis cases in the 1970s cohort and 2.0 times (708 cases) more mumps orchitis cases in the 1980s cohort than complications coded to mumps in hospital databases. Our study demonstrated that the mumps outbreak in England 2004/05 resulted in a substantial increase in hospitalised mumps complications, and the model we used can improve the ascertainment of morbidity from a mumps outbreak. PMID- 27562959 TI - Preparation of Underrepresented Males for Scientific Careers: A Study of the Dr. John H. Hopps Jr. Defense Research Scholars Program at Morehouse College. AB - Equal representation within higher education science, technology, engineering, and mathematics (STEM) fields and the STEM workforce in the United States across demographically diverse populations is a long-standing challenge. This study uses two-to-one nearest-neighbor matched-comparison group design to examine academic achievement, pursuit of graduate science degree, and classification of graduate institution attended by students participating in the Hopps Scholars Program (Hopps) at Morehouse College. Hopps is a highly structured enrichment program aimed at increasing participation of black males in STEM fields. Morehouse institutional records, Hopps Program records, and National Student Clearinghouse data were used to examine differences between Hopps and non-Hopps STEM graduates of Morehouse. Two-way sample t tests and chi-square tests revealed significant differences in academic achievement, likelihood of STEM degree pursuit, and the classification of graduate institutions attended by Hopps versus non-Hopps students. Hopps Scholars were significantly more likely than non-Hopps STEM graduates both to pursue STEM doctoral degrees and to attend doctoral-granting institutions with higher research activity. The Hopps Program's approach to training black male students for scientific careers is a model of success for other programs committed to increasing the number of black males pursuing advanced degrees in STEM. PMID- 27562961 TI - Psychosocial Pathways to STEM Engagement among Graduate Students in the Life Sciences. AB - Despite growing diversity among life sciences professionals, members of historically underrepresented groups (e.g., women) continue to encounter barriers to academic and career advancement, such as subtle messages and stereotypes that signal low value for women, and fewer opportunities for quality mentoring relationships. These barriers reinforce the stereotype that women's gender is incompatible with their science, technology, engineering, and mathematics (STEM) field, and can interfere with their sense of belonging and self-efficacy within STEM. The present work expands this literature in two ways, by 1) focusing on a distinct period in women's careers that has been relatively understudied, but represents a critical period when career decisions are made, that is, graduate school; and 2) highlighting the buffering effect of one critical mechanism against barriers to STEM persistence, that is, perceived support from advisors. Results of the present study show that perceived support from one's advisor may promote STEM engagement among women by predicting greater gender-STEM identity compatibility, which in turn predicts greater STEM importance among women (but not men). STEM importance further predicts higher sense of belonging in STEM for both men and women and increased STEM self-efficacy for women. Finally, we describe the implications of this work for educational policy. PMID- 27562960 TI - Principles and Practices Fostering Inclusive Excellence: Lessons from the Howard Hughes Medical Institute's Capstone Institutions. AB - Best-practices pedagogy in science, technology, engineering, and mathematics (STEM) aims for inclusive excellence that fosters student persistence. This paper describes principles of inclusivity across 11 primarily undergraduate institutions designated as Capstone Awardees in Howard Hughes Medical Institute's (HHMI) 2012 competition. The Capstones represent a range of institutional missions, student profiles, and geographical locations. Each successfully directed activities toward persistence of STEM students, especially those from traditionally underrepresented groups, through a set of common elements: mentoring programs to build community; research experiences to strengthen scientific skill/identity; attention to quantitative skills; and outreach/bridge programs to broaden the student pool. This paper grounds these program elements in learning theory, emphasizing their essential principles with examples of how they were implemented within institutional contexts. We also describe common assessment approaches that in many cases informed programming and created traction for stakeholder buy-in. The lessons learned from our shared experiences in pursuit of inclusive excellence, including the resources housed on our companion website, can inform others' efforts to increase access to and persistence in STEM in higher education. PMID- 27562962 TI - The Benefits of Attending the Annual Biomedical Research Conference for Minority Students (ABRCMS): The Role of Research Confidence. AB - The Annual Biomedical Research Conference for Minority Students (ABRCMS) is designed to support undergraduate students' professional development as future scientists. Juniors, seniors, and postbaccalaureates who attended ABRCMS during 2008-2011 were emailed a link to an online questionnaire in which they reported their experiences at the conference. Attendees reported many ABRCMS-provided benefits. Frequency of attending or presenting at ABRCMS is positively related to science self-efficacy, research confidence, sense of belonging in science, and intentions to pursue a research degree in graduate school. Increased research confidence predicts graduate school plans and intentions for a research career in science; however, men were slightly more likely to intend to pursue a research career than women, likely due to higher research confidence. Although all attendees benefited from ABRCMS, underrepresented minority (URM) students had higher science self-efficacy and sense of belonging in science after attending ABRCMS than non-URM students. This finding demonstrates the effectiveness of ABRCMS as an intervention to increase the representation and success of URMs in science. Results highlight the importance of attending a minority-oriented research conference where URMs can develop their science self-efficacy, research confidence, and sense of belonging in science. However, changes to the conference and undergraduate research experiences may be necessary to reduce gender gaps. PMID- 27562963 TI - Recent advances in sequence-based protein structure prediction. AB - The most accurate characterizations of the structure of proteins are provided by structural biology experiments. However, because of the high cost and labor intensive nature of the structural experiments, the gap between the number of protein sequences and solved structures is widening rapidly. Development of computational methods to accurately model protein structures from sequences is becoming increasingly important to the biological community. In this article, we highlight some important progress in the field of protein structure prediction, especially those related to free modeling (FM) methods that generate structure models without using homologous templates. We also provide a short synopsis of some of the recent advances in FM approaches as demonstrated in the recent Computational Assessment of Structure Prediction competition as well as recent trends and outlook for FM approaches in protein structure prediction. PMID- 27562964 TI - Quetiapine Carboxylic Acid and Quetiapine Sulfoxide Prevalence in Patient Urine. AB - Treatment adherence is often an issue with mental health patients. For those prescribed quetiapine (Seroquel(r)), the low levels of parent drug and plasma metabolite(s) (e.g., 7-hydroxyquetiapine) typically used in urine drug monitoring can result in false negatives with concomitant unfavorable impacts on patient care. Literature review coupled with liquid chromatography/time-of-flight mass spectrometry analysis of patient positive urine samples indicated the presence of quetiapine carboxylic acid and quetiapine sulfoxide as significant urinary metabolites of quetiapine. Analysis of these two metabolites determined that they are abundant in the urine of quetiapine patients and can result in apparent adherence rates that are improved relative to those determined using only quetiapine and 7-hydroxyquetiapine. For example, analysis of a random set of 114 patients who were prescribed quetiapine exhibited an apparent adherence rate of 47% using the quetiapine carboxylic acid and quetiapine sulfoxide metabolites. Traditional metabolite testing with quetiapine and 7-hydroxyquetiapine yielded apparent adherence rates of ~31% while all four analytes resulted in apparent adherence of 48%. The prevalence of these metabolites suggests that quetiapine urine drug testing would be more consistent with prescriptions when they are included in the analysis. PMID- 27562965 TI - Analysis of Valproic Acid, Salicylic Acid and Ibuprofen in Whole Blood by GC-MS. AB - The Georgia Bureau of Investigation utilized a silylation method of analysis for low molecular weight carboxylic acids in the past. Due to the negative impact such derivatizations can have on gas chromatography-mass spectrometry (GC-MS) systems an alternative means of analysis was investigated. The described method is a whole blood solid phase extraction of valproic acid, salicylic acid and ibuprofen utilizing butylation for sensitivity and improved chromatography by GC MS. The method produced a limit of detection and limit of quantitation at 1 mg/L for valproic acid, 2 mg/L for salicylic acid and 0.25 mg/L for ibuprofen. The variability based upon the middle of the calibration curve estimated to be 7% for valproic acid, 8% for salicylic acid and 11% for ibuprofen established upon a 95% confidence interval, with the highest percent coefficient of variation being 5.3% for ibuprofen. PMID- 27562966 TI - LC-MS-MS Method for the Analysis of Miscellaneous Drugs in Wastewater During Football Games III. AB - Continuing our previous studies analyzing drugs of abuse in municipal wastewater, a method was developed for the analysis of miscellaneous drugs of abuse in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Eight drugs and metabolites were analyzed including 2 ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine (EDDP), fentanyl, norfentanyl, meperidine, normeperidine, methadone, phencyclidine and tramadol. These drugs were chosen because of their widespread abuse. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. These wastewater samples were collected on weekends in which the University of Mississippi football team (colloquially the "Ole Miss Rebels" football team) held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain tramadol in 25 samples at quantifiable levels. EDDP, meperidine, normeperidine and methadone were also detected but were under the limit of quantitation. PMID- 27562967 TI - Illicit Drug Analysis Using Two-Dimension Liquid Chromatography/Tandem Mass Spectrometry. AB - For the identification of illicit drugs in forensic toxicological casework, analysis can be delayed and potentially compromised due to lengthy sample preparation techniques. For a complete forensic identification, a robust methodology is required and the current trend in forensic laboratories is the use of liquid chromatography coupled to mass spectrometry (LC/MS or LC/MS-MS). However, to achieve satisfactory results, extensive and time-consuming sample preparation protocols are required to reach sub-ng/mL levels. The concept of sequential 2D extraction was designed to capture the retention behavior of a target analyte in response to various extraction parameters. Therefore, optimized conditions can be selected to excise a region of interest during extraction. The utilization of multi-dimensional chromatography combined with a micro-extraction technique was evaluated to decrease sample preparation time while enhancing the separation integrity observed with current single-dimensional chromatography techniques. A wide range of illicit drugs were spiked in human urine and extracted using three extraction protocols for performance evaluation. The extraction process was performed using a reversed-phase solid phase extraction (SPE) in 1D, 2D-optimized, 2D-sequential and cumulative elution modes. The chosen 2D chromatography conditions that were used in this application were identified using a 6 * 6 automated methods development protocol (144 methods total). The extraction of urine samples containing target analytes was completed in less than 20 min. The analysis was performed using 200 uL of the final organic solvent (MeOH) extracts. The limit of detection for all drugs was measured at 100 pg/mL (ppt) from a 1 mL sample volume. Several analytes showed excellent signal at 10 pg/mL (ppt). PMID- 27562968 TI - Definitive Drug and Metabolite Screening in Urine by UPLC-MS-MS Using a Novel Calibration Technique. AB - Drug screening is an essential analytical tool for detection of therapeutic, illicit and emerging drug use. Presumptive immunoassay screening is widely used, while initial definitive testing by chromatography-coupled mass spectrometry is hampered due to complex pre-analysis steps, long chromatography time and matrix effects. The aim of this study is to develop and validate a definitive test for rapid and threshold accurate screening of 33 drugs or metabolites (analytes) in urine. Sample preparation in a 96-well plate format involves rapid glucuronidase hydrolysis followed by dilution, filtration and ultra-performance liquid chromatography-MS-MS analysis. Chromatographic separation, on an ACQUITY UPLC(r) BEH phenyl column is optimized for a 3-min MS-MS ion acquisition. Matrix effect was normalized by an innovative technique called threshold accurate calibration employing an additional analysis with an analyte spike as an internal standard undergoing the same matrix effect as an analyte in a drug-positive donor specimen. Accuracy and precision, at above and below threshold concentrations, were determined by replicate analysis of control urine pools containing 50, 75, 125 and 150% of threshold concentrations. Accuracy and selectivity were further demonstrated by concordant findings in proficiency and confirmatory testing. The study shows the applicability of definitive testing as an alternative to immunoassay screening and demonstrates a new approach to normalization of matrix effect. PMID- 27562969 TI - Evaluation of a Newly Formulated Enzyme Immunoassay for the Detection of Hydrocodone and Hydromorphone in Pain Management Compliance Testing. AB - A new Hydrocodone Enzyme Immunoassay (HEIA; Lin-Zhi International, Inc.) was evaluated for the detection of hydrocodone and its main metabolite, hydromorphone. All specimens were tested with two different cutoff calibrators, 100 and 300 ng/mL, on an ARCHITECT Plus c4000 Clinical Chemistry Analyzer. Controls containing -25% (negative control) and +25% (positive control) of the cutoff calibrators and a drug-free control were analyzed with each batch. All 1,025 urine specimens were previously analyzed by ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS-MS) for opiates. Approximately, 33% (337/1,019) of the specimens yielded positive results by the HEIA assay at a cutoff concentration of 100 ng/mL and 19% (190/1,025) yielded positive results at the 300 ng/mL cutoff concentration. Of these presumptive positive specimens, UPLC-MS-MS confirmed the presence of hydrocodone and/or hydromorphone >100 ng/mL in 241 specimens and >300 ng/mL in 162 specimens, for each respective cutoff. With the 100 ng/mL cutoff, the HEIA demonstrated a sensitivity of 0.959, a specificity of 0.846 and an overall agreement with the UPLC-MS-MS of 87%. At 300 ng/mL cutoff, the HEIA demonstrated a sensitivity of 0.880, a specificity of 0.966 and an overall agreement of UPLC-MS-MS results of 95%. The Lin-Zhi HEIA 100 ng/mL cutoff assay demonstrated sensitivity for the detection of hydrocodone and hydromorphone in urine. The 300 ng/mL cutoff was less sensitive, but more selective, and should be part of an initial immunoassay screen, particularly in pain management compliance testing. PMID- 27562970 TI - Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Decomposition in Different Microclimate Conditions. AB - The effects of decomposition microclimate on the distribution of dextromethorphan (DXM) and dextrorphan (DXT) in skeletonized remains of rats acutely exposed to DXM were examined. Animals (n = 10) received DXM (75 mg/kg, i.p.), were euthanized 30 min post-dose and immediately allowed to decompose at either Site A (shaded forest microenvironment on a grass-covered soil substrate) or Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Ambient temperature and relative humidity were automatically recorded 3 cm above rats at each site. Skeletal elements (vertebral columns, ribs, pelvic girdles, femora, tibiae, humeri and scapulae) were harvested, and analyzed using microwave assisted extraction, microplate solid phase extraction, and GC/MS. Drug levels, expressed as mass-normalized response ratios, and the ratios of DXT and DXM levels were compared across bones and between microclimate sites. No significant differences in DXT levels or metabolite/parent ratios were observed between sites or across bones. Only femoral DXM levels differed significantly between microclimate sites. For pooled data, microclimate was not observed to significantly affect analyte levels, nor the ratio of levels of DXT and DXM. These data suggest that microclimate conditions do not influence DXM and metabolite distribution in skeletal remains. PMID- 27562972 TI - Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold Normal Saline). AB - BACKGROUND: Patients successfully resuscitated by paramedics from out-of-hospital cardiac arrest often have severe neurologic injury. Laboratory and observational clinical reports have suggested that induction of therapeutic hypothermia during cardiopulmonary resuscitation (CPR) may improve neurologic outcomes. One technique for induction of mild therapeutic hypothermia during CPR is a rapid infusion of large-volume cold crystalloid fluid. METHODS: In this multicenter, randomized, controlled trial we assigned adults with out-of-hospital cardiac arrest undergoing CPR to either a rapid intravenous infusion of up to 2 L of cold saline or standard care. The primary outcome measure was survival at hospital discharge; secondary end points included return of a spontaneous circulation. The trial was closed early (at 48% recruitment target) due to changes in temperature management at major receiving hospitals. RESULTS: A total of 1198 patients were assigned to either therapeutic hypothermia during CPR (618 patients) or standard prehospital care (580 patients). Patients allocated to therapeutic hypothermia received a mean (SD) of 1193 (647) mL cold saline. For patients with an initial shockable cardiac rhythm, there was a decrease in the rate of return of a spontaneous circulation in patients who received cold saline compared with standard care (41.2% compared with 50.6%, P=0.03). Overall 10.2% of patients allocated to therapeutic hypothermia during CPR were alive at hospital discharge compared with 11.4% who received standard care (P=0.71). CONCLUSIONS: In adults with out-of-hospital cardiac arrest, induction of mild therapeutic hypothermia using a rapid infusion of large-volume, intravenous cold saline during CPR may decrease the rate of return of a spontaneous circulation in patients with an initial shockable rhythm and produced no trend toward improved outcomes at hospital discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01173393. PMID- 27562973 TI - Sonography of Morton Neuromas: What Are We Really Looking At? AB - OBJECTIVES: To determine what accounts for the sonographic appearance of a Morton neuroma by correlating preoperative sonograms with the sonographic appearance of the resected surgical specimen, the surgical findings, and the pathologic examination. METHODS: Ten Morton neuromas that had preoperative sonograms underwent postoperative specimen sonography and histologic evaluation. The appearance and size of the neuromas were compared between the preoperative and postoperative specimen images and were compared to the surgical and pathologic appearances. RESULTS: Preoperative images showed a fibrillar echogenic nerve coursing into a heterogeneous hypoechoic mass measuring 14.3 mm in average length (range, 9.0-24.0 mm) that contained a round, mildly echogenic mass within it measuring 7.6 mm in average length (range, 4.5-12.0 mm). Surgically, the specimens showed scarred intermetatarsal bursas and tangled vessels surrounding the nerve. Specimen sonography showed echogenic focal enlargement of the nerve at the site of the neuroma, measuring 6.8 mm in average length (range, 3.5-11.0 mm). The size of the resected neuroma was smaller than the hypoechoic mass on the presurgical images (P < .001). Within the hypoechoic mass, the small echogenic focus showed no difference in size compared to the specimen (P = .40), but the shape of the echogenic specimen was fusiform, whereas the preoperative appearance was round. Histologically, the resected specimens showed sclerosis and mucoid degeneration of the nerve fascicles and fibrotic thickening of the perineurium. CONCLUSIONS: The hypoechoic heterogeneous mass that is referred to as a Morton neuroma sonographically is really a "neuroma-bursal complex" that is much larger than the actual neuroma itself. PMID- 27562971 TI - Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1. AB - BACKGROUND: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1). METHODS: RNA sequencing, quantitative polymerase chain reaction,13C-nuclear magnetic resonance, fluorescence-lifetime imaging, mass spectrometry-based metabolomics, and tracing experiments with U-13C-glucose were used to assess glycolytic reprogramming and to measure the NADH/NAD+ ratio in bovine and human adventitial fibroblasts and mouse lung tissues. Immunohistochemistry was used to assess CtBP1 expression in the whole-lung tissues. CtBP1 siRNA and the pharmacological inhibitor 4 methylthio-2-oxobutyric acid (MTOB) were used to abrogate CtBP1 activity in cells and hypoxic mice. RESULTS: We found that adventitial fibroblasts from calves with severe hypoxia-induced PH and humans with idiopathic pulmonary arterial hypertension (PH-Fibs) displayed aerobic glycolysis when cultured under normoxia, accompanied by increased free NADH and NADH/NAD+ ratios. Expression of the NADH sensor CtBP1 was increased in vivo and in vitro in fibroblasts within the pulmonary adventitia of humans with idiopathic pulmonary arterial hypertension and animals with PH and cultured PH-Fibs, respectively. Decreasing NADH pharmacologically with MTOB or genetically blocking CtBP1 with siRNA upregulated the cyclin-dependent genes (p15 and p21) and proapoptotic regulators (NOXA and PERP), attenuated proliferation, corrected the glycolytic reprogramming phenotype of PH-Fibs, and augmented transcription of the anti-inflammatory gene HMOX1. Chromatin immunoprecipitation analysis demonstrated that CtBP1 directly binds the HMOX1 promoter. Treatment of hypoxic mice with MTOB decreased glycolysis and expression of inflammatory genes, attenuated proliferation, and suppressed macrophage numbers and remodeling in the distal pulmonary vasculature. CONCLUSIONS: CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target. PMID- 27562974 TI - Is Ultrasonography More Sensitive Than Computed Tomography for Identifying Calcifications in Thyroid Nodules? AB - OBJECTIVES: The primary objective of this study was to evaluate the difference and agreement between ultrasonography (US) and computed tomography (CT) for identifying calcifications in thyroid nodules. METHODS: Data from the medical records of 20,248 patients were reviewed for preoperative diagnostic investigations and postoperative pathologic diagnoses. In total, 5247 records were selected for analysis based on the presence of calcifications reported in any of the following 3 modes: US, CT, and pathologic analysis. All 5247 patients underwent US examinations, whereas 3827 underwent cervical CT examinations. All patients had a postoperative pathologic diagnosis serving as a reference. The value of US for identification of calcifications and prediction of malignancy was analyzed on the basis of the entire cohort of 5247 records, whereas that of CT was based on 3827 records. The agreement between US and CT was analyzed on the basis of the 3827 common records. RESULTS: Of the 5247 patients who underwent US, 4855 (92.5%) were found to have calcifications, whereas of the 3827 patients who underwent CT, 2040 (53.3%) were found to have calcifications (P < .0005). Among the 404 cases with calcifications reported by pathologic analysis, the agreement rate between US and pathologic findings was significantly higher than that between CT and pathologic findings (87.9% versus 81.9%, respectively; P = .018). CONCLUSIONS: US is more sensitive and accurate than CT for detecting calcifications in thyroid nodules. Hence, US is recommended as the preferred imaging modality for calcification detection in thyroid nodules. PMID- 27562975 TI - Methodology for Using 3-Dimensional Sonography to Measure Fetal Adrenal Gland Volumes in Pregnant Women With and Without Early Life Stress. AB - Fetal adrenal gland volumes on 3-dimensional sonography have been studied as potential predictors of preterm birth. However, no consistent methodology has been published. This article describes the methodology used in a study that is evaluating the effects of maternal early life stress on fetal adrenal growth to allow other researchers to compare methodologies across studies. Fetal volumetric data were obtained in 36 women at 20 to 22 and 28 to 30 weeks' gestation. Two independent examiners measured multiple images of a single fetal adrenal gland from each sonogram. Intra- and inter-rater consistency was examined. In addition, fetal adrenal volumes between male and female fetuses were reported. The intra- and inter-rater reliability was satisfactory when the mean of 3 measurements from each rater was used. At 20 weeks' gestation, male fetuses had larger average adjusted adrenal volumes than female fetuses (mean, 0.897 versus 0.638; P = .004). At 28 weeks' gestation, the fetal weight was more influential in determining values for adjusted fetal adrenal volume (0.672 for male fetuses versus 0.526 for female fetuses; P = .034). This article presents a methodology for assessing fetal adrenal volume using 3-dimensional sonography that can be used by other researchers to provide more consistency across studies. PMID- 27562976 TI - Ultrasound-Guided Ureteral Stent Removal in Women. AB - OBJECTIVES: The purpose of this study was to develop a fast, comfortable, and safe method of ureteral stent removal in women. METHODS: From February 2014 to July 2015, a retrospective multicenter controlled study including 82 female outpatients was conducted. The control group was composed of 46 patients who underwent stent removal using a 22F cystoscope. The experimental group was composed of 36 patients who underwent stent removal under ultrasound guidance with a 15F spiral-ending device. Exclusion criteria were pelvic organ prolapse quantification stage II or higher and complicated stents (with migration or encrustation). RESULTS: All studied patients had successful ureteral stent removal. No complications were seen in both groups. Differences between mean visual analog pain scale scores and stent removal durations were statistically significant in favor of the experimental group (P = .0077 and .0075, respectively). CONCLUSIONS: The proposed method for ureteral stent removal in women under ultrasound guidance was shown to be faster and to have lower visual analog pain scale scores, in comparison with removal by a cystoscope, which makes it an attractive option for outpatient urologic praxis in uncomplicated cases, and because it is free of the risk of ionizing radiation and more comfortable, it can be used in pregnant patients. PMID- 27562977 TI - Color Doppler Imaging of the Appendix: Criteria to Improve Specificity for Appendicitis in the Borderline-Size Appendix. AB - OBJECTIVES: To test the hypothesis that continuous intramural vascular signal measuring at least 3 mm on color Doppler imaging is highly specific for appendicitis in patients with diagnostically borderline-size appendices. METHODS: Two blinded observers independently reviewed color Doppler images of the appendix in 94 consecutive patients who had undergone sonography for suspected appendicitis and whose appendices were of diagnostically borderline size (6-8 mm maximum outer diameter). Intramural vascular flow on color Doppler images was classified as absent, type 1 (only punctate and dispersed signal), or type 2 (continuous linear or curvilinear signal measuring at least 3.0 mm in long- or short-axis views). Histopathologic examination and clinical follow-up served as reference standards. Proportions were assessed by the exact binomial test. RESULTS: Of the 94 patients, 33 (35.1%) had type 1 flow (of whom 5 [15.2%] had appendicitis); 23 (24.5%) had type 2 flow (of whom 20 [87.0%] had appendicitis); and 38 (40.4%) had absent flow (of whom 10 [26.3%] had appendicitis). The sensitivity, specificity, and odds ratio of type 2 flow as an indicator of appendicitis were 57.1%, 94.9%, and 24.9 (P< .001), respectively; the corresponding values for type 1 flow as an indicator of normal appendices were and 47.5%, 85.7%, and 5.4 (P = .002). CONCLUSIONS: Continuous intramural linear or curvilinear signal measuring at least 3 mm on color Doppler imaging is a highly specific, although relatively insensitive, sign of acute appendicitis in noncompressible appendices of diagnostically borderline size (6-8 mm). PMID- 27562978 TI - Measurement of the Human Calcaneus In Vivo Using Ultrasonic Backscatter Spectral Centroid Shift. AB - OBJECTIVES: The aim of this study was to determine the relationship between the backscattered spectral centroid shift and the bone mineral density (BMD) in vivo and investigate the feasibility of using the backscattered spectral centroid shift to characterize the cancellous bone status. METHODS: Ultrasonic backscatter measurements were performed in vivo on 1216 participants at the right calcaneus using an ultrasonic backscattered bone diagnostic system, and the backscattered spectral centroid shift was calculated at central frequencies of 3.5 and 5.0 MHz. The BMD values were measured at the sites of the lumbar spine and left hip by dual energy x-ray absorptiometry. RESULTS: The study population included 592 male and 624 female participants aged 20 to 89 years. The correlations between the backscattered spectral centroid shift in the calcaneus and the spine and hip BMD were found to be statistically significant in both the male and female groups (P < .0001). Linear regression showed that the spectral centroid shift at 3.5 MHz had negative correlations with the spine BMD (R = -0.65 for male participants; R = -0.67 for female participants) and hip BMD (R = -0.64 for male participants; R = -0.64 for female participants). The spectral centroid shift at 5.0 MHz was also found to be closely related to the spine BMD (R = -0.68 for male participants; R = -0.68 for female participants) and hip BMD (R = -0.66 for male participants; R = -0.64 for female participants). CONCLUSIONS: The moderate correlations observed between the spectral centroid shift and the spine and hip BMD demonstrate that the ultrasonic backscattered spectral centroid shift may be a useful measurement for assessment of the cancellous bone status. PMID- 27562979 TI - Development and initial validation of the Cat HEalth and Wellbeing (CHEW) Questionnaire: a generic health-related quality of life instrument for cats. AB - OBJECTIVES: The aims of the study were to define factors that owners consider relevant to the health-related quality of life (HRQoL) of cats, to develop an instrument based on this information, and to evaluate the validity and reliability of the final instrument (the Cat HEalth and Wellbeing [CHEW] Questionnaire). METHODS: Psychometric research techniques and guidance from the US Food and Drug Administration on outcome measures were used to develop a valid and reliable instrument. Fifty-four cat owners and caregivers participated in the qualitative research, while 1303 cat owners were included in the quantitative validation phase (development dataset, n = 648; validation dataset, n = 655). A random subset of cat owners (n = 391) also participated in test-retest evaluation. Qualitative research was used to generate a draft instrument, which was then subjected to quantitative validation techniques. These included item reduction, domain identification, data quality assessment, and exploratory and confirmatory analysis to develop a final instrument, which underwent confirmatory reliability and validity assessment. RESULTS: A draft instrument with 11 domains and 100 items based on qualitative research underwent online quantitative validation testing which refined the instrument to eight domains and 33 items. Confirmatory reliability and validity assessment showed that the final instrument had good validity, was able to discriminate between cats by age and overall health status, and demonstrated good internal and test-retest reliability. CONCLUSIONS AND RELEVANCE: The CHEW Questionnaire was developed and validated. Additional research is needed to verify its ability to differentiate cats with and without disease, and to assess its potential as a screening tool. PMID- 27562980 TI - Eye examination in the cat: Step-by-step approach and common findings. AB - PRACTICAL RELEVANCE: The ability to perform a complete eye examination in the cat is critically important for patients with an ocular disorder or a systemic disease, as well as for the geriatric cat. CLINICAL CHALLENGES: Cats may need short breaks between portions of the eye exam in order to minimize stress. For the clinician, use of ophthalmic equipment and interpretation of normal vs abnormal findings may take some practice in order to develop proficiency. AUDIENCE: This review is aimed at veterinary practitioners and outlines all the steps and equipment necessary to perform a complete ophthalmic examination in the cat. EQUIPMENT: Although some specialized equipment is required, a complete eye exam can be performed with a modest investment in equipment and supplies. EVIDENCE BASE: This article draws on published references for normal parameters measured in the feline eye exam, as well as the experience of the authors. PMID- 27562981 TI - Feline Calcium Oxalate Urolithiasis: Risk factors and rational treatment approaches. AB - PRACTICAL RELEVANCE: Uroliths occur commonly in the bladder and/or urethra of cats and can be lifethreatening if urethral obstruction occurs. Calcium oxalate accounts for 40-50% of urocystoliths and these stones are not amenable to medical dissolution; therefore, removal by surgery or minimally invasive techniques is required if uroliths must be treated. Medical protocols for prevention involve decreasing urine saturation for minerals that form uroliths. ETIOPATHOGENESIS: Formation of uroliths is not a disease, but rather a complication of several disorders. Some disorders can be identified and corrected (such as infection induced struvite urolith formation); others can be identified but not corrected (such as idiopathic hypercalcemia). In most cats with calcium oxalate urolith formation the underlying etiopathogenesis is not known. A common denominator of all these disorders is that they can from time to time create oversaturation of urine with one or more crystal precursors, resulting in formation of crystals. BASIC CONCEPTS: In order to develop rational and effective approaches to treatment, abnormalities that promote urolith formation must be identified, with the goal of eliminating or modifying them. It is important, therefore, to understand several basic concepts associated with urolithiasis and the factors that promote urolith formation that may be modified with medical treatment; for example, the state of urinary saturation, modifiers of crystal formation, potential for multiple crystal types, and presence of bacterial infection or urinary obstruction. PMID- 27562982 TI - New Approaches to Feline Diabetes Mellitus: Glucagon-like peptide-1 analogs. AB - CLINICAL RELEVANCE: Incretin-based therapies are revolutionizing the field of human diabetes mellitus (DM) by replacing insulin therapy with safer and more convenient long-acting drugs. MECHANISM OF ACTION: Incretin hormones (glucagon like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) are secreted from the intestinal tract in response to the presence of food in the intestinal lumen. GLP-1 delays gastric emptying and increases satiety. In the pancreas, GLP-1 augments insulin secretion and suppresses glucagon secretion during hyperglycemia in a glucose-dependent manner. It also protects beta cells from oxidative and toxic injury and promotes expansion of beta cell mass. ADVANTAGES: Clinical data have revealed that GLP-1 analog drugs are as effective as insulin in improving glycemic control while reducing body weight in people suffering from type 2 DM. Furthermore, the incidence of hypoglycemia is low with these drugs because of their glucose-dependent mechanism of action. Another significant advantage of these drugs is their duration of action. While insulin injections are administered at least once daily, long-acting GLP-1 analogs have been developed as once-a-week injections and could potentially be administered even less frequently than that in diabetic cats. OUTLINE: This article reviews the physiology of incretin hormones, and the pharmacology and use of GLP-1 analogs, with emphasis on recent research in cats. Further therapies that are based on incretin hormones, such as DPP-4 inhibitors, are also briefly discussed, as are some other treatment modalities that are currently under investigation. PMID- 27562983 TI - 2016 AAFP Guidelines for the Management of Feline Hyperthyroidism. PMID- 27562984 TI - News & Views. PMID- 27562985 TI - Violence against emergency department employees and the attitude of employees towards violence. AB - INTRODUCTION: This study was conducted to evaluate the occurrence of violent incidents in the workplace among the various professional groups working in the emergency department. We characterised the types of violence encountered by different occupation groups and the attitude of individuals working in different capacities. METHODS: This cross-sectional study included 323 people representing various professional groups working in two distinct emergency departments in Turkey. The participants were asked to complete questionnaires prepared in advance by the researchers. The data were analysed using the Statistical Package for the Social Sciences (Windows version 15.0). RESULTS: A total of 323 subjects including 189 (58.5%) men and 134 (41.5%) women participated in the study. Their mean (+/- standard deviation) age was 31.5 +/- 6.5 years and 32.0 +/- 6.9 years, respectively. In all, 74.0% of participants had been subjected to verbal or physical violence at any point since starting employment in a medical profession. Moreover, 50.2% of participants stated that they had been subjected to violence for more than 5 times. Among those who reported being subjected to violence, 42.7% had formally reported the incident(s). Besides, 74.3% of participants did not enjoy their profession, did not want to work in the emergency department, or would prefer employment in a non-health care field after being subjected to violence. According to the study participants, the most common cause of violence was the attitude of patients or their family members (28.7%). In addition, 79.6% (n=257) of participants stated that they did not have adequate safety protection in their working area. According to the study participants, there is a need for legal regulations to effectively deter violence and increased safety measures designed to reduce the incidence of violence in the emergency department. CONCLUSION: Violence against employees in the emergency department is a widespread problem. This situation has a strong negative effect on employee satisfaction and work performance. In order to reduce the incidence of violence in the emergency department, both patients and their families should be better informed so they have realistic expectations as an emergency patient, deterrent legal regulations should be put in place, and increased efforts should be made to provide enhanced security for emergency department personnel. These measures will reduce workplace violence and the stress experienced by emergency workers. We expect this to have a positive impact on emergency health care service delivery. PMID- 27562986 TI - Primary ventriculoperitoneal shunting outcomes: a multicentre clinical audit for shunt infection and its risk factors. AB - OBJECTIVES: To determine the frequency of primary ventriculoperitoneal shunt infection among patients treated at neurosurgical centres of the Hospital Authority and to identify underlying risk factors. METHODS: This multicentre historical cohort study included consecutive patients who underwent primary ventriculoperitoneal shunting at a Hospital Authority neurosurgery centre from 1 January 2009 to 31 December 2011. The primary endpoint was shunt infection, defined as: (1) the presence of cerebrospinal fluid or shunt hardware culture that yielded the pathogenic micro-organism with associated compatible symptoms and signs of central nervous system infection or shunt malfunction; or (2) surgical incision site infection requiring shunt reinsertion (even in the absence of positive culture); or (3) intraperitoneal pseudocyst formation (even in the absence of positive culture). Secondary endpoints were shunt malfunction, defined as unsatisfactory cerebrospinal fluid drainage that required shunt reinsertion, and 30-day mortality. RESULTS: A primary ventriculoperitoneal shunt was inserted in 538 patients during the study period. The mean age of patients was 48 years (range, 13-88 years) with a male-to-female ratio of 1:1. Aneurysmal subarachnoid haemorrhage was the most common aetiology (n=169, 31%) followed by intracranial tumour (n=164, 30%), central nervous system infection (n=42, 8%), and traumatic brain injury (n=27, 5%). The mean operating time was 75 (standard deviation, 29) minutes. Shunt reinsertion and infection rates were 16% (n=87) and 7% (n=36), respectively. The most common cause for shunt reinsertion was malfunction followed by shunt infection. Independent predictors for shunt infection were: traumatic brain injury (adjusted odds ratio=6.2; 95% confidence interval, 2.3 16.8), emergency shunting (2.3; 1.0-5.1), and prophylactic vancomycin as the sole antibiotic (3.4; 1.1-11.0). The 30-day all-cause mortality was 6% and none were directly procedure-related. CONCLUSIONS: This is the first Hong Kong territory wide review of infection in primary ventriculoperitoneal shunts. Although the ventriculoperitoneal shunt infection rate met international standards, there are areas of improvement such as vancomycin administration and the avoidance of scheduling the procedure as an emergency. PMID- 27562987 TI - Management of health care workers following occupational exposure to hepatitis B, hepatitis C, and human immunodeficiency virus. AB - INTRODUCTION: Needlestick injury or mucosal contact with blood or body fluids is well recognised in the health care setting. This study aimed to describe the post exposure management and outcome in health care workers following exposure to hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) during needlestick injury or mucosal contact. METHODS: This case series study was conducted in a public clinic in Hong Kong. All health care workers with a needlestick injury or mucosal contact with blood or body fluids who were referred to the Therapeutic Prevention Clinic of Department of Health from 1999 to 2013 were included. RESULTS: A total of 1525 health care workers were referred to the Therapeutic Prevention Clinic following occupational exposure. Most sustained a percutaneous injury (89%), in particular during post-procedure cleaning or tidying up. Gloves were worn in 62.7% of instances. The source patient could be identified in 83.7% of cases, but the infection status was usually unknown, with baseline positivity rates of hepatitis B, hepatitis C, and HIV of all identified sources, as reported by the injured, being 7.4%, 1.6%, and 3.3%, respectively. Post-exposure prophylaxis of HIV was prescribed to 48 health care workers, of whom 14 (38.9%) had been exposed to known HIV-infected blood or body fluids. The majority (89.6%) received HIV post-exposure prophylaxis within 24 hours of exposure. Drug-related adverse events were encountered by 88.6%. The completion rate of post-exposure prophylaxis was 73.1%. After a follow-up period of 6 months (or 1 year for those who had taken HIV post-exposure prophylaxis), no hepatitis B, hepatitis C, or HIV seroconversions were detected. CONCLUSIONS: Percutaneous injury in the health care setting is not uncommon but post-exposure prophylaxis of HIV is infrequently indicated. There was no hepatitis B, hepatitis C, and HIV transmission via sharps or mucosal injury in this cohort of health care workers. PMID- 27562988 TI - Diabetic retinopathy screening: global and local perspective. AB - Diabetes mellitus has become a global epidemic. It causes significant macrovascular complications such as coronary artery disease, peripheral artery disease, and stroke; as well as microvascular complications such as retinopathy, nephropathy, and neuropathy. Diabetic retinopathy is known to be the leading cause of blindness in the working-age population and may be asymptomatic until vision loss occurs. Screening for diabetic retinopathy has been shown to reduce blindness by timely detection and effective laser treatment. Diabetic retinopathy screening is being done worldwide either as a national screening programme or hospital-based project or as a community-based screening programme. In this article, we review different methods of screening including grading used to detect the severity of sight-threatening retinopathy and the newer screening methods. This review also includes the method of systematic screening being carried out in Hong Kong, a system that has helped to identify diabetic retinopathy among all attendees in public primary care clinics using a Hong Kong wide public patients' database. PMID- 27562989 TI - [Prospects for the design of new therapeutically significant protease inhibitors based on knottins and sunflower seed trypsin inhibitor (SFTI 1)]. AB - Plant seed knottins, mainly from the Cucurbitacea family, and sunflower seed trypsin inhibitor (SFTI 1) are the most low-molecular canonical peptide inhibitors of serine proteases. High efficiency of inhibition of various serine proteases, structure rigidity together with the possibility of limited variations of amino acid sequences, high chemical stability, lack of toxic properties, opportunity of production by either chemical synthesis or use of heterologous expression systems make these inhibitors attractive templates for design of new compounds for regulation of therapeutically significant serine protease activities. Hence the design of such compounds represents a prospective research field. The review considers structural characteristics of these inhibitors, their properties, methods of preparation and design of new analogs. Examples of successful employment of natural serine protease inhibitors belonging to knottin family and SFTI 1 as templates for the design of highly specific inhibitors of certain proteases are given. PMID- 27562990 TI - [Composition and biological activity of triterpenes and steroids from Inonotus obliquus (chaga)]. AB - Data on the chemical composition of triterpenic and steroid compounds, isolated from the chaga mushroom grown in natural environment or in a synthetic culture have been summarized. Special attention has been paid to the biological activity of chaga mushroom extracts and these particular compounds against various cancer cell lines in vitro and in vivo. This analysis has demonstrated some common features in inhibition of growth of various cell lines by chaga mushroom components. In this context, the most active are triterpene compounds containing OH group at C-22 and a side chain unsaturated bond. PMID- 27562991 TI - [Oncolytic viruses for therapy of malignant glioma]. AB - Effective treatment of malignant brain tumors is still an open problem. Location of tumor in vital areas of the brain significantly limits capasities of surgical treatment. The presence of tumor stem cells resistant to radiation and anticancer drugs in brain tumor complicates use of chemoradiotherapy and causes a high rate of disease recurrence. A technological improvement in bioselection and production of recombinant resulted in creation of viruses with potent oncolytic properties against glial tumors. Recent studies, including clinical trials, showed, that majority of oncolytic viruses are safe. Despite the impressive results of the viral therapy in some patients, the treatment of other patients is not effective; therefore, further improvement of the methods of oncolytic virotherapy is necessary. High genetic heterogeneity of glial tumor cells even within a single tumor determines differences in individual sensitivity of tumor cells to oncolytic viruses. This review analyses the most successful oncolytic virus strains, including those which had reached clinical trials, and discusses the prospects for new approaches to virotherapy of gliomas. PMID- 27562992 TI - [Atherogenic modification of low-density lipoproteins]. AB - One of the first manifestations of atherosclerosis is accumulation of extra- and intracellular cholesterol esters in the arterial intima. Formation of foam cells is considered as a trigger in the pathogenesis of atherosclerosis. Low density lipoprotein (LDL) circulating in human blood is the source of lipids accumulated in the arterial walls. This review considered features and role in atherogenesis different modified forms of LDL: oxidized, small dense, electronegative and especially desialylated LDL. Desialylated LDL of human blood plasma is capable to induce lipid accumulation in cultured cells and it is atherogenic. LDL possesses numerous alterations of protein, carbohydrate and lipid moieties and therefore can be termed multiple-modified LDL. Multiple modification of LDL occurs in human blood plasma and represents a cascade of successive changes in the lipoprotein particle: desialylation, loss of lipids, reduction in the particle size, increase of surface electronegative charge, etc. In addition to intracellular lipid accumulation, stimulatory effects of naturally occurring multiple-modified LDL on other processes involved in the development of atherosclerotic lesions, namely cell proliferation and fibrosis, were shown. PMID- 27562993 TI - [Digital droplet PCR - a prospective technological approach to quantitative profiling of microRNA]. AB - MicroRNA is a special type of regulatory molecules governing gene expression. Circulating microRNAs found in blood and other biological fluids are considered today as potential biomarkers of human pathology. Presently, quantitative alterations of particular microRNAs are revealed for a large number of oncological diseases and other disorders. The recently emerged method of digital droplet PCR (ddPCR) possesses a number of advantages making this method the most suitable for verification and validation of perspective microRNA markers of human pathologies. Among these advantages are the high accuracy and reproducibility of microRNA quantification as well as the capability to directly measure the absolute number of microRNA copies with the large dynamic range and a high throughput. The paper reviews microRNA biogenesis, the origin of circulating microRNAs, and methods used for their quantification. The special technical features of ddPCR, which make it an attractive method both for studying microRNAs as biomarkers of human pathologies and for basic research devoted to aspects of gene regulation by microRNA molecules, are also discussed. PMID- 27562994 TI - [DNA aptamers selection for breast cancer]. AB - A method of selection of DNA aptamers to breast tumor tissue based on the use of postoperative material has been developed. Breast cancer tissues were used as the positive target; the negative targets included benign tumor tissue, adjacent healthy tissues, breast tissues from mastopathy patients, and also tissues of other types of malignant tumors. During selection a pool of DNA aptamers demonstrating selective binding to breast cancer cells and tissues and insignificant binding to breast benign tissues has been obtained. These DNA aptamers can be used for identification of protein markers, breast cancer diagnostics, and targeted delivery of anticancer drugs. PMID- 27562995 TI - [Tumor necrosis fastor-alpha - potential target for neuroprotector dimebon]. AB - Dimebon (Dimebolin) is an antihistamine drug which has been used in Russia since 1983. Recently Dimebolin has attracted renewed interest after being shown to have positive effects on persons suffering from Alzheimer's disease. Animal studies have shown that dimebon acts through multiple mechanisms, both blocking the action of neurotoxic beta-amyloid peptides and inhibiting L-type calcium channels, modulating the action of AMPA and NMDA glutamate receptors. Our experiments with cell culture L929 and mice have shown that dimebon may exert its neuroprotective effect by blocking cytotoxic signals induced by proinflammatory cytokines such as TNF-a which are believed to play a central role in Alzheimer's disease. Dimebon (10 mg/ml) protected mouse fibroblasts L929 against the toxic action of TNF-a. Our study included 65 male mice. TNF-a (10 mg per mouse), dimebon (0,2 mg/kg) and their combination were injected intraperitonealy. Changes in the level of molecular species of sphingomyelin and galactosyl ceramide in hippocampus, cerebellum and cerebral cortex within 30 min, 2 h, 4 h, and 24 h after injection were detected by chromato-mass-spectrometry. Maximal changes in sphingomyelin and galactosyl ceramides contents of different molecular species after single TNF-a administration were found in the hippocampus, and were less expressed in the cerebral cortex and cerebellum after 24 h. Dimebon itself did not induce changes in the sphingolipid spectrum in brain sections, but protected them against disorders induced by TNF-a in the brain. Modern strategies in the search of new therapeutic approaches are based on the multitarget properties of new drugs. According to our results TNF-a may serve as a new target for dimebon. PMID- 27562996 TI - [The effect of fenofibrate on expression of genes involved in fatty acids beta oxidation and associated free-radical processes]. AB - Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria. Enhancement of oxidative processes caused a 2-fold increase in the rate of reactive oxygen species (ROS) production, as evidenced by determination of the level of lipid peroxidation (LPO) products in the liver. Mitochondrial antioxidant systems are more sensitive to elevated ROS production, as they respond by increased expression of SOD2 and PRDX3 genes, than cytoplasmic and peroxisomal antioxidant systems, where expression of CAT1, SOD1, PRDX5 genes remained unaltered. PMID- 27562997 TI - [Thiol peroxidase activities in rat blood plasma determined with hydrogen peroxide and 5,5'-dithio-bis(2-nitrobenzoic acid)]. AB - Earlier it has been shown that extracellular glutathione peroxidase (GPx3) from human plasma is able to use cysteine (Cys-SH) instead of glutathione (GSH) as a thiol substrate. In the present study, the ability of rat plasma to utilize not only GSH, but also Cys-SH and homocysteine (Hcy-SH), in the thiol peroxidase reaction has been confirmed. The molar ratio between thiol and H2O2 in the catalyzed reaction was 2:1. The specific activity increased with fractionation of proteins. At a fixed thiol concentration of 0.23 mM, the saturation by H2O2 with vmax app of 100, 128, and 132 nmol H2O2 / s per 1 ml of plasma was found for DL Cys-SH, L-GSH, and DL-Hcy-SH, respectively. Rank distributions of activities towards all three thiol substrates within plasma protein fractions are fully identical (the probability of random full coincidence was less than 0.01). The statistical analysis confirms that Cys-SH peroxidase, Hcy-SH peroxidase, and GSH peroxidase activities are closely associated with each other. The most probable outcome of this result is the ability of rat GPx3 to utilize all three thiols as substrates for oxidation. Probably, thiol peroxidase is a participant of formation of plasma cystine (Cys-SS-Cys) from Cys-SH in plasma. If the forms of Hcy exhibit different toxic effects, it can be suggested that thiol peroxidase regulates Hcy toxicity in hyperhomocysteinemia through Hcy-SH oxidation to homocystine (Hcy-SS-Hcy). PMID- 27562998 TI - [AFM fishing of proteins under impulse electric field]. AB - A combination of (atomic force microscopy)-based fishing (AFM-fishing) and mass spectrometry allows to capture protein molecules from solutions, concentrate and visualize them on an atomically flat surface of the AFM chip and identify by subsequent mass spectrometric analysis. In order to increase the AFM-fishing efficiency we have applied pulsed voltage with the rise time of the front of about 1 ns to the AFM chip. The AFM-chip was made using a conductive material, highly oriented pyrolytic graphite (HOPG). The increased efficiency of AFM fishing has been demonstrated using detection of cytochrome b5 protein. Selection of the stimulating pulse with a rise time of 1 ns, corresponding to the GHz frequency range, by the effect of intrinsic emission from water observed in this frequency range during water injection into the cell. PMID- 27562999 TI - [Pathogenetic significance of C774T single nucleotide polymorphism of the endothelial NO synthase gene in the development of metabolic syndrome]. AB - The relationship between nitric oxide production and metabolic disorders and the role of endothelial nitric oxide synthase (eNOS or NOS3) in metabolic syndrome (MS) remain poorly understood and need deeper investigation. In this context the role of the NOS3 gene in pathogenesis of MS is of special interest. The aim of the study was to investigate association of NOS3 single nucleotide polymorphism C774T with risk of MS in the Slavic population of the Kaliningrad region and the relationship of this polymorphic variant with some parameters of endothelial dysfunction. The study included 128 patients (48 men and 80 women aged from 36 to 52 years) with MS. The control group consisted of 126 healthy volunteers (60 men and 66 women aged from 30 to 40 years). Genotyping was performed by real-time PCR. Serum nitrite levels were determined spectrophotometrically by the Griess method. Serum levels of endothelin-1 and eNOS were evaluated by ELISA. The study has shown association of T allele (OR=2.06; p=0.0004; CI: 1.38-3.08) and CT genotype (OR=1.97; p=0.014; CI: 1.14-3.40 ) C774T polymorphism of the NOS3 gene with risk of MS in the Slavic population of the Kaliningrad region. Allele C (OR=0.48; p=0.0004; CI: 0.32-0.72) and homozygous CC genotype (OR=0.41; p=0.001; CI: 0.24-0,69) C774T polymorphism of the NOS3 gene were associated with reduced risk of the development of MS. Significant differences in serum levels of eNOS and endothelin-1 depended on the CT and TT genotypes of C774T polymorphism of the NOS3 gene in MS. PMID- 27563000 TI - [Mammaglobin in peripheral blood and tumor in breast cancer patients]. AB - Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p=0.0019). The maximal expression level was in the samples T1 (p=0.013), stage I BC (p=0.037), GI (p=0.0019). The MGB1 expression positively correlated with expression of estrogen (p = 0,034) and progesterone (p=0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6% and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method. PMID- 27563001 TI - [Biochemical and immunological markers of autoimmune thyroiditis]. AB - Correlations between biochemical and immunological markers of programmed cell death (apoptosis), and the functional state of the thyroid gland (hyperthyroidism, euthyroidism, hypothyroidism) have been investigated in autoimmune thyroiditis (AT) (also known as chronic autoimmune thyroiditis). Annexin V, TRAIL and TNF-a, as well as DNA-hydrolyzing antibodies were used as the main markers. Increased levels of TRAIL were found in the serum of AT patients (hyperthyroidism>hypothyroidism>euthyroidism) compared with healthy individuals. The highest frequency of antibodies to denatured DNA (Abs-dDNA) had the highest frequency in AT patients (97%) compared with healthy controls. Among these patients, 75% had hyperthyroidism, 85% had hypothyroidism, and 84.7% had euthyroidism. Abs hydrolyzing activity demonstrated correlation dependence with symptoms of the thyroid dysfunction. PMID- 27563002 TI - [The maternal effect in infantile autism: elevated DNA damage degree in patients and their mothers]. AB - Infantile autism is a common disorder of mental development, which is characterized by impairments in the communicative, cognitive and speech spheres and obsessional stereotyped behaviour. Although in most cases, pathogenic factors remain unclear, infantile autism has a significant hereditary component, however, its etiology is also under the influence of environmental factors, including the condition of the mother's body during pregnancy ("maternal effect"). Oxidative stress is assumed to play a key role in the pathogenesis of infantile autism. It is known that oxidative stress has a prominent genotoxic effect, which is realized through inducing single and double strand breaks of the nuclear DNA. We evaluated the degree of DNA damage in patients with infantile autism and their mothers using DNA comet assay. The comet tail moment and DNA per cent ratio in the tail were assessed for each individual. The two parameters appeared to be strongly correlated (r=0.90). Mean and median values of both parameters were considerably higher in the sample of autistic children, than in age-matching healthy controls. Interestingly, these parameters were also elevated in healthy mothers of autistic children, with no difference from the values in the group of autistic children. The control group of healthy women of reproductive age, who had no children with autism, differed by the DNA comet tail moment from the group of mothers of autistic children, but did not differ significantly from the control group of healthy children. The results suggest that there are genotoxic factors in mentally healthy mothers of autistic children, which can determine the pathological process in the foeti via environmental "maternal effect" during gestation. PMID- 27563003 TI - [Antibodies against modified low-density lipoproteins and their complexes in blood of patients with various manifestations of atherosclerosis]. AB - The study included 79 patients with coronary artery disease, 25 individuals with preclinical atherosclerosis and 59 healthy controls. Key lipid parameters were examined in all the participants. Levels of antibodies (Abs) against (IgG and IgM) LDL modified by malondialdehyde (MDA), acetic anhydride and hypochlorite, were determined by the enzyme-linked immunosorbent assay (ELISA). Abs specificity was tested by competitive ELISA. Circulating immune complexes (CIC) were isolated by precipitation in polyethylene glycol. Abs to hypochlorite-modified low density lipoprotein (hypochlorite-LDL) were detected in the serum samples. These Abs did not demonstrate cross-reactivity with MDA-modified LDL (MDA-LDL) and acetylated LDL (acetyl-LDL). Patients with coronary artery disease had increased levels of CIC (p<0.0001) and decreased levels of Abs (IgM) to hypochlorite-LDL, compared with healthy controls and patients with preclinical atherosclerosis (p=0.006). A correlation between the levels of Abs (IgG) to the hypochlorite-LDL and Abs to MDA- and acetyl-LDL was found. There was a correlation between the content of the Abs (IgM) to MDA- and acetyl-LDL and the concentration of CIC-cholesterol. Lipid parameters did not correlate with Abs levels. PMID- 27563004 TI - Structure features of GH10 xylanase from Caldicellulosiruptor bescii: implication for its thermophilic adaption and substrate binding preference. AB - Caldicellulosiruptor bescii is the most thermophilic cellulolytic species of organisms known to date. In our previous study, GH10 xylanase CbXyn10B from C. bescii displayed outstanding hydrolytic activity toward various xylans at high temperatures. To understand the structural basis for this protein's catalysis and thermostability, we solved the crystal structures of CbXyn10B and its complexes with xylooligosaccharides. These structural models were used to guide comparison with its mesophilic counterpart PbXyn10B. A distinctive structural feature is that thermophilic CbXyn10B presents a relatively stable interaction between the extended loops L7 and L8 in the catalytic cleft by an extensive hydrogen bonding network, which is mediated by Lys306, Arg314 and three well-ordered water molecules. Moreover, a unique aromatic cluster consisting of Try17, Phe20, Phe21, and Phe337 may enhance the interaction between the N- and C- terminus. Targeted mutagenesis demonstrated that these interactions substantially contribute to enzyme stabilization, as indicated by a considerable decrease in the melting temperature (Tm) of CbXyn10B by substituting critical residues with Ala. Therefore, it was shown that not only the aromatic interaction connecting protein termini but also the extensive hydrogen bonding network formed between surface loops could restrict the local structural flexibility and contribute significantly to the overall stability of enzymes. Furthermore, the xylooligosaccharides were found to tightly bind to the glycone subsites of xylanase, indicating higher affinities at these subsites and reflecting its substrate binding preference. Our results suggest that CbXyn10B is stabilized with distinct rigidity at the catalytic cleft as well as the terminal regions, which provides insights into the evolutionary strategy for accommodating the functional needs of GH10 enzymes to high temperature. PMID- 27563005 TI - miR-378 attenuates muscle regeneration by delaying satellite cell activation and differentiation in mice. AB - Skeletal muscle mass and homeostasis during postnatal muscle development and regeneration largely depend on adult muscle stem cells (satellite cells). We recently showed that global overexpression of miR-378 significantly reduced skeletal muscle mass in mice. In the current study, we used miR-378 transgenic (Tg) mice to assess the in vivo functional effects of miR-378 on skeletal muscle growth and regeneration. Cross-sectional analysis of skeletal muscle tissues showed that the number and size of myofibers were significantly lower in miR-378 Tg mice than in wild-type mice. Attenuated cardiotoxin-induced muscle regeneration in miR-378 Tg mice was found to be associated with delayed satellite cell activation and differentiation. Mechanistically, miR-378 was found to directly target Igf1r in muscle cells both in vitro and in vivo These miR-378 Tg mice may provide a model for investigating the physiological and pathological roles of skeletal muscle in muscle-associated diseases in humans, particularly in sarcopenia. PMID- 27563006 TI - Anti-nociceptive roles of the glia-specific metabolic inhibitor fluorocitrate in paclitaxel-evoked neuropathic pain. AB - Paclitaxel (Taxol) is a powerful chemotherapy drug used in breast cancers, but it often causes neuropathic pain, leading to the early cessation of therapy and poor treatment outcomes. Approaches for the management of paclitaxel-induced neuropathic pain are urgently needed. The involvement of spinal astrocytes in the pathogenesis of paclitaxel-induced neuropathy has been reported, but little is known about the role of fluorocitrate (FC), a selective inhibitor of astrocyte activation, during neuropathic pain related to paclitaxel treatment. In this study, we investigated the effects of FC on paclitaxel-induced neuropathic pain. Glial fibrillary acidic protein (GFAP) expression was determined to assess astrocyte activation. To explore the mechanisms involved, the expression of glial glutamate transporter 1 (GLT-1) and the activation of mitogen-activated protein kinases in the spinal dorsal horn were analyzed. The results showed that paclitaxel decreased the mechanical nociceptive thresholds and increased GFAP expression, leading to spinal astrocyte activation. After paclitaxel treatment, GLT-1 was significantly down-regulated, and the phosphorylation of ERK1/2 and JNK were obviously up-regulated. However, paclitaxel treatment did not increase p38 phosphorylation. Additional studies showed that paclitaxel-evoked mechanical hypersensitivity was reduced by FC treatment. Moreover, FC treatment inhibited the activation of astrocytes and reversed the changes in GLT-1 expression and MAPK phosphorylation. Further study indicated that FC did not influence the antitumor effect of paclitaxel, suggesting that FC blocked paclitaxel-induced neuropathic pain without antagonizing its antitumor effect. Together, these results suggested that paclitaxel induced astrocyte-specific activation, which may contribute to mechanical allodynia and hyperalgesia, and that FC could be a potential therapeutic agent for paclitaxel-induced neuropathic pain. PMID- 27563007 TI - Activation of Na+/K+-ATPase attenuates high glucose-induced H9c2 cell apoptosis via suppressing ROS accumulation and MAPKs activities by DRm217. AB - Hyperglycemia is one of the major factors responsible for the myocardial apoptosis and dysfunction in diabetes. Many studies have proved that there is a close relationship between decreased Na+/K+-ATPase activity and diabetic cardiomyopathy. However, the effect of directly activated Na+/K+-ATPase on high glucose-induced myocardial injury is still unknown. Here we found that DRm217, a Na+/K+-ATPase's DR-region specific monoclonal antibody and direct activator, could prevent high glucose-induced H9c2 cell injury, reactive oxygen species (ROS) release, and mitochondrial dysfunction. High glucose-treatment decreased Na+/K+-ATPase activity and increased intracellular Ca2+ level, whereas DRm217 increased Na+/K+-ATPase activity and alleviated Ca2+ overload. Inhibition of Ca2+ overload or closing sodium calcium exchanger (NCX channel) could reverse high glucose-induced ROS increasing and cell injury. In addition, DRm217 could significantly attenuate high glucose-induced p38, JNK and ERK1/2 phosphorylation, which were involved in high glucose-induced cell injury and ROS accumulation. Our findings suggest that DRm217 may protect against the deleterious effects of high glucose in the heart. Prevention of high glucose-induced myocardial cell injury by specific Na+/K+-ATPase activator may be an attractive therapeutic option. PMID- 27563008 TI - Human galectin-2 interacts with carbohydrates and peptides non-classically: new insight from X-ray crystallography and hemagglutination. AB - Galectin-2 (Gal-2) plays a role in cancer, myocardial infarction, immune response, and gastrointestinal tract diseases. The only reported crystal structure of Gal-2 shows that it is a dimer in which the monomer subunits have almost identical structures, each binding with one molecule of lactose. In this study, we crystallized Gal-2 under new conditions that produced three crystal structures. In each Gal-2 dimer structure, lactose was shown to be bound to only one of the carbohydrate recognition domain subunits. In solution studies, the thermal shift assay demonstrated that inequivalent monomer subunits in the Gal-2 dimer become equivalent upon ligand binding. In addition, galectin-mediated erythrocyte agglutination assays using lactose and larger complex polysaccharides as inhibitors showed the structural differences between Gal-1 and Gal-2. Overall, our results reveal some novel aspects to the structural differentiation in Gal-2 and expand the potential for different types of molecular interactions that may be specific to this lectin. PMID- 27563009 TI - NEK7: a novel promising therapy target for NLRP3-related inflammatory diseases. PMID- 27563010 TI - A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages. AB - Mycobacterium tuberculosis (Mtb) is a Gram-positive pathogen which causes tuberculosis in both animals and humans. All tested rH-NS formulations induced a specific Th1 response, as indicated by increased production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) by lymphocytes in the spleen of mice which were immunized with rH-NS alone or with rH-NS and the adjuvant cyclic GMP-AMP (cGAMP). Serum from mice immunized with rH-NS with or without adjuvant also had higher levels of IL-12p40 and TNF-alpha, compared with those from control mice immunized with phosphate-buffered saline. Both vaccines increased protective efficacy in mice which were challenged with Mtb H37Rv, as measured by reduced relative CFU counts in the lungs. We found that rH-NS induced the production of TNF-alpha, IL-6, and IL-12p40, which relied on the activation of mitogen activated protein kinases by stimulating the rapid phosphorylation of ERK1/2, p38, and JNK, and on the activation of transcription factor NF-kappaB in macrophages. Additionally, we also found that rH-NS could interact with TLR2 but not TLR4 in pull-down assays. The rH-NS-induced cytokine production from TLR2 silenced RAW264.7 cells was lower than that from BALB/c macrophages. Prolonged exposure (>24 h) of RAW264.7 cells to rH-NS resulted in a significant enhancement in IFN-gamma-induced MHC II expression, which was not found in shTLR2-treated RAW264.7 cells. These results suggest that rH-NS is a TLR2 agonist which induces the production of cytokines by macrophages and up-regulates macrophage function. PMID- 27563011 TI - MiR-630 inhibits invasion and metastasis in esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is among the most aggressive malignancies and has a high incidence in China. MicroRNAs (miRNAs) are small endogenous RNAs that regulate multiple tumorigenic processes, including proliferation, invasion, metastasis and prognosis. Using miRNA expression profiling analysis, we found that miR-630 was markedly down-regulated in three ESCC tissue samples compared with that in paired normal esophageal tissues. Differential miR-630 expression was subsequently confirmed using quantitative real-time PCR. To determine whether miR-630 down-regulation could be considered as a diagnostic indicator and adverse prognostic factor, we investigated the association between miR-630 and clinicopathological characteristics in patients with ESCC. It was found that decreased miR-630 expression was associated with poor overall survival in these patients. In addition, we also explored the biological function of miR-630 by targeting Slug and investigated the correlation between miR-630 expression and epithelial-mesenchymal transition (EMT) progression in vivo and in vitro Ectopic miR-630 expression could inhibit proliferation, invasion and metastasis, whereas miR-630 knockdown induced proliferation, invasion, metastasis and EMT traits. Overall, our study supports a role for miR-630 as a critical novel modulator in ESCC. PMID- 27563012 TI - Factors Influencing Parent Reports of Facilitators and Barriers to Human Milk Supply in Neonatal Intensive Care Units. AB - BACKGROUND: Successful human milk supply in neonatal intensive care units (NICUs) requires the development of family-centered services. OBJECTIVE: This study aimed to assess parent perceptions of factors that help or hinder providing human milk to very preterm infants (VPI) in the NICU according to sociodemographic, reproductive, and obstetric characteristics. METHODS: This cross-sectional quantitative study included 120 mothers and 91 fathers of VPI hospitalized in a level 3 NICU located in the Northern Health Region of Portugal (July 2013-June 2014). Interviewers administered structured questionnaires regarding parent characteristics and the provision and perception of factors that help or hinder human milk supply in the NICU, 15 to 22 days after birth. RESULTS: The main facilitators of human milk supply were its contribution to infant growth and well being (51.4%) and parents' knowledge of breastfeeding benefits (27.6%). The main barriers were worries related to inadequate milk supply (35.7%), difficulties with expressing breast milk (24.8%), and physical separation from infants (24.3%). Fathers referred less frequently to the contribution of human milk to infant growth and well-being (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.32-1.00) but more frequently to knowledge of breastfeeding benefits as facilitators (OR = 2.31; 95% CI, 1.23-4.32). Participants with > 12 years of education (OR = 1.91; 95% CI, 1.05-3.47) and those with an extremely low birth weight infant (OR = 1.90; 95% CI, 1.02-3.54) highlighted worries related to inadequate milk supply. Fathers (OR = 2.16; 95% CI, 1.11-4.19) and participants with <= 12 years of education (OR = 0.25; 95% CI, 0.11-0.57) more frequently reported difficulties with expressing as the main barrier. CONCLUSION: The parent's gender and education and the infant's birth weight are crucial considerations for establishing optimal practices for supporting breastfeeding. PMID- 27563013 TI - Maternal Buprenorphine Maintenance and Lactation. AB - BACKGROUND: In addition to the well-known benefits of human milk and breastfeeding for the mother and infant, breastfeeding may mitigate neonatal abstinence syndrome severity in prenatally opioid-exposed infants. However, lack of conclusive data regarding the extent of the presence of buprenorphine and active metabolites in human milk makes the recommendation of breastfeeding for buprenorphine-maintained women difficult for many providers. OBJECTIVE: This study seeks to determine the concentrations of buprenorphine and its active metabolites (norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine glucuronide) in human milk, maternal plasma, and infant plasma of buprenorphine maintained women and their infants. METHODS: Up to 10 buprenorphine-maintained women provided paired breast milk and plasma samples at 2, 3, 4, 14, and 30 days postdelivery, and 9 infants provided plasma samples on day 14 of life. All samples were analyzed via liquid chromatography tandem mass spectrometry to determine concentrations of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine-glucuronide by a fully validated method. RESULTS: Concentrations of buprenorphine and metabolites are low in human milk and maternal plasma. Breastfed infant plasma concentrations of buprenorphine were low or undetectable and metabolite concentrations undetectable at 14 days of infant age. There were significant correlations between maternal buprenorphine dose and maternal plasma and human milk buprenorphine concentrations. CONCLUSION: These data find low concentrations of buprenorphine and metabolites in human milk and lend support to the recommendation for lactation among stable buprenorphine maintained women. However, the correlation between maternal dose and maternal plasma and human milk buprenorphine concentrations bears further study. PMID- 27563014 TI - How Can We Propagate the National Endoscopy Quality Improvement Program and Improve the Quality of Endoscopic Screening? PMID- 27563015 TI - Helicobacter pylori Eradication Therapy, the Reasonable First Line Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Irrespective of Infection Status and Disease Stages. PMID- 27563016 TI - Nonzero Risk of Hepatocellular Carcinoma Even after Sustained Virological Response. PMID- 27563017 TI - The Clinical Utility of MicroRNA as a Prognostic Biomarker of Pancreatobiliary Cancers. PMID- 27563018 TI - The Role of Common Pharmaceutical Agents on the Prevention and Treatment of Pancreatic Cancer. AB - Survival from pancreatic cancer remains poor. Conventional treatment has resulted in only marginal improvements in survival compared with survival in the previous several decades. Thus, considerable interest has emerged regarding the potential use of common pharmaceutical agents as chemopreventative and chemotherapeutic options. Aspirin, metformin, statins, beta-blockers, and bisphosphonates have biologically plausible mechanisms to inhibit pancreatic neoplasia, whereas dipeptidyl-peptidase 4 inhibitors may promote it. Regardless, real-world epidemiological data remain inconclusive. This review examines the hypotheses, evidence, and current state of the literature for each of these medications and their potential roles in the prevention and treatment of pancreatic cancer. PMID- 27563019 TI - Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions. AB - Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including nonalcoholic fatty liver disease, will be elaborated. PMID- 27563022 TI - Survey of Anxiety in Ordinary Workers and Doctors Regarding Sedative Use during Endoscopic Examination in the Seoul Metropolitan Area. AB - BACKGROUND/AIMS: Sedative use is common in endoscopic examinations. The anxiety regarding sedative use may be different between doctors and nonmedical individuals. METHODS: A questionnaire survey was conducted by a research company (DOOIT Survey), and responses were collected from 649 doctors and 1,738 individuals who perform typical jobs in nonmedical fields. In this study, these ordinary workers are considered to represent nonmedical individuals. Anxiety was measured using a 5-point Likert scale. RESULTS: The nonmedical individuals exhibited more anxiety regarding the sedative use than the doctors. Age <40 years (odds ratio [OR], 2.27; p<0.001), female sex (OR, 1.62; p=0.002), experience of an adverse event (OR, 1.79; p=0.049), and insufficient explanation (OR, 2.05; p<0.001) were the significant factors that increased the anxiety of the nonmedical individuals. The doctors who experienced a sedative-related adverse event reported increased anxiety compared with the doctors who did not report this experience (OR, 1.73; p=0.031). CONCLUSIONS: Anxiety regarding sedative use during an endoscopic examination was significantly different between doctors and non-medical individuals. A younger age, female sex, an adverse event, and insufficient explanation affect the anxiety of nonmedical individuals. An adverse event also affects the anxiety of doctors. PMID- 27563021 TI - The Efficacy of a Newly Designed, Easy-to-Manufacture Training Simulator for Endoscopic Biopsy of the Stomach. AB - BACKGROUND/AIMS: We developed a new endoscopic biopsy training simulator and determined its efficacy for improving the endoscopic biopsy skills of beginners. METHODS: This biopsy simulator, which presents seven biopsy sites, was constructed using readily available materials. We enrolled 40 participants: 14 residents, 11 first-year clinical fellows, 10 second-year clinical fellows, and five staff members. We recorded the simulation completion time for all participants, and then simulator performance was assessed via a questionnaire using the 7-point Likert scale. RESULTS: The mean times for completing the five trials were 417.7+/-138.8, 145.2+/-31.5, 112.7+/-21.9, and 90.5+/-20.0 seconds for the residents, first-year clinical fellows, second-year clinical fellows, and staff members, respectively. Endoscopists with less experience reported that they found this simulator more useful for improving their biopsy technique (6.8+/-0.4 in the resident group and 5.7+/-1.0 in the first-year clinical fellow group). The realism score of the simulator for endoscopic handling was 6.4+/-0.5 in the staff group. CONCLUSIONS: This new, easy-to-manufacture endoscopic biopsy simulator is useful for biopsy training for beginner endoscopists and shows good efficacy and realism. PMID- 27563020 TI - Biology of Cholangiocytes: From Bench to Bedside. AB - Cholangiocytes, the lining epithelial cells in bile ducts, are an important subset of liver cells. They are activated by endogenous and exogenous stimuli and are involved in the modification of bile volume and composition. They are also involved in damaging and repairing the liver. Cholangiocytes have many functions including bile production. They are also involved in transport processes that regulate the volume and composition of bile. Cholangiocytes undergo proliferation and cell death under a variety of conditions. Cholangiocytes have functional and morphological heterogenecity. The immunobiology of cholangiocytes is important, particularly for understanding biliary disease. Secretion of different proinflammatory mediators, cytokines, and chemokines suggests the major role that cholangiocytes play in inflammatory reactions. Furthermore, paracrine secretion of growth factors and peptides mediates extensive cross-talk with other liver cells, including hepatocytes, stellate cells, stem cells, subepithelial myofibroblasts, endothelial cells, and inflammatory cells. Cholangiopathy refers to a category of chronic liver diseases whose primary disease target is the cholangiocyte. Cholangiopathy usually results in end-stage liver disease requiring liver transplant. We summarize the biology of cholangiocytes and redefine the concept of cholangiopathy. We also discuss the recent progress that has been made in understanding the pathogenesis of cholangiopathy and how such progress has influenced therapy. PMID- 27563023 TI - The Effect of the First Spontaneous Bacterial Peritonitis Event on the Mortality of Cirrhotic Patients with Ascites: A Nationwide Population-Based Study in Taiwan. AB - BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) contributes to poorer short-term mortality in cirrhotic patients with ascites. However, it is unknown how long the effect of the first SBP event persists in these patients. METHODS: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify and enroll 7,892 cirrhotic patients with ascites who were hospitalized between January 1 and December 31, 2007. All patients were free from episodes of SBP from 1996 to 2006. RESULTS: The study included 1,176 patients with SBP. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in this group were 21.8%, 38.9%, 57.5%, and 73.4%, respectively. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in the non-SBP group were 15.7%, 32.5%, 53.3%, and 72.5%, respectively. After adjusting for gender, age, and other medical comorbidities, the adjusted hazard ratios of SBP for 30-day, 30- to 90-day, 90-day to 1-year, and 1- to 3-year mortality were 1.49 (95% confidence interval [CI], 1.30 to 1.71), 1.19 (95% CI, 1.02 to 1.38), 1.04 (95% CI, 0.90 to 1.20), and 0.90 (95% CI, 0.77 to 1.05), respectively, compared with the non-SBP group. CONCLUSIONS: The effect of SBP on the mortality of cirrhotic patients with ascites disappeared in those surviving more than 90 days after the first SBP event. PMID- 27563024 TI - MUC Expression in Gallbladder Epithelial Tissues in Cholesterol-Associated Gallbladder Disease. AB - BACKGROUND/AIMS: Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. METHODS: The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. RESULTS: MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. CONCLUSIONS: The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression. PMID- 27563025 TI - The construction of three-dimensional composite fibrous macrostructures with nanotextures for biomedical applications. AB - The development of modern biomedical nanotechnology requires three-dimensional macrostructures with nanotextures to meet the requirements for practical applications in intricate biological systems. Additionally, the restoration and regeneration of some specific body tissues and organs rely on the function of conductive polymers, which can provide electrical cues for cells. In this study, we fabricated three-dimensional composite nanofibre macrostructures of polycaprolactone (PCL) with different concentrations of polyaniline (PANi) by employing an improved electrospinning technology with a specially designed collector. The 3D structures possessed cap-like macrostructures with centimetre scale thickness and interconnected pore nanotextures with nanometre-scale nanofibres. To estimate the biocompatibility of the 3D PCL/PANi composite nanofibre macrostructures, mouse myoblasts (C2C12 cells) were cultured as model cells. The initial responses of C2C12 cells to the 3D PCL/PANi composite macrostructures were significantly superior to those to pure PCL, that is, the cells exhibited typical myoblast-like morphologies with obvious pseudopodia and the moderate incorporation (less than 2.0 wt%) of conductive PANi facilitated cell proliferation, which indicated that PANi has appreciable cell affinity. Moreover, the addition of conductive PANi to the 3D composite nanofibre macrostructures considerably enhanced myoblast differentiation and myotube maturation. These results suggest that electrospun 3D PCL/PANi composite nanofibre macrostructures would have promising applications in tissue engineering. PMID- 27563026 TI - LoFtool: a gene intolerance score based on loss-of-function variants in 60 706 individuals. AB - Motivation: Depletion of loss-of-function (LoF) mutations may provide a rank of genic functional intolerance and consequently susceptibility to disease. Results: Here we have studied LoF mutations in 60 706 unrelated individuals and show that the most intolerant quartile of ranked genes is enriched in rare and early onset diseases and explains 87% of de novo haploinsufficient OMIM mutations, 17% more than any other gene scoring tool. We detected particular enrichment in expression of the depleted LoF genes in brain (odds ratio = 1.5; P -value = 4.2e-07). By searching for de novo haploinsufficient mutations putatively associated with neurodevelopmental disorders in four recent studies, we were able to explain 81% of them. Taken together, this study provides a novel gene intolerance ranking system, called LoFtool, which may help in ranking genes of interest based on their LoF intolerance and tissue expression. Availability and implementation: The LoFtool gene scores are available in the Supplementary data . Contact: joaofadista@gmail.com. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 27563028 TI - Menstruating Mice. PMID- 27563029 TI - Fabrication of type I collagen microcarrier using a microfluidic 3D T-junction device and its application for the quantitative analysis of cell-ECM interactions. AB - We presented a new quantitative analysis for cell and extracellular matrix (ECM) interactions, using cell-coated ECM hydrogel microbeads (hydrobeads) made of type I collagen. The hydrobeads can carry cells as three-dimensional spheroidal forms with an ECM inside, facilitating a direct interaction between the cells and ECM. The cells on hydrobeads do not have a hypoxic core, which opens the possibility for using as a cell microcarrier for bottom-up tissue reconstitution. This technique can utilize various types of cells, even MDA-MB-231 cells, which have weak cell-cell interactions and do not form spheroids in conventional spheroid culture methods. Morphological indices of the cell-coated hydrobead visually present cell-ECM interactions in a quantitative manner. PMID- 27563027 TI - Prediction of nucleosome positioning by the incorporation of frequencies and distributions of three different nucleotide segment lengths into a general pseudo k-tuple nucleotide composition. AB - MOTIVATION: Nucleosome positioning plays important roles in many eukaryotic intranuclear processes, such as transcriptional regulation and chromatin structure formation. The investigations of nucleosome positioning rules provide a deeper understanding of these intracellular processes. RESULTS: Nucleosome positioning prediction was performed using a model consisting of three types of variables characterizing a DNA sequence-the number of five-nucleotide sequences, the number of three-nucleotide combinations in one period of a helix, and mono- and di-nucleotide distributions in DNA fragments. Using recently proposed stringent benchmark datasets with low biases for Saccharomyces cerevisiae, Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster, the present model was shown to have a better prediction performance than the recently proposed predictors. This model was able to display the common and organism-dependent factors that affect nucleosome forming and inhibiting sequences as well. Therefore, the predictors developed here can accurately predict nucleosome positioning and help determine the key factors influencing this process. CONTACT: awa@hiroshima-u.ac.jpSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27563030 TI - An in vitro vascular chip using 3D printing-enabled hydrogel casting. AB - An important unsolved challenge in tissue engineering has been the inability to replicate the geometry and function of vascular networks and blood vessels. Here, we engineer a user-defined 3D microfluidic vascular channel using 3D printing enabled hydrogel casting. First, a hollow L-shaped channel is developed using a template casting process. In this process, murine 10T1/2 cells are encapsulated within gelatin methacrylate (GelMA) hydrogel using UV photocrosslinking, and upon removal of the template results in a hollow channel within GelMA. Second, human umbilical vein endothelial cells (HUVECs) were cultured within the channel and immunostaining was used to visualize endothelial monolayers. Third, diffusion/permeability studies on endothelialized channels were carried out to demonstrate the barrier function of HUVEC monolayer. Taken together, we develop a facile, cytocompatible and rapid approach to engineer a user-defined multicellular vascular chip that could be potentially useful in developing new vascular model systems. PMID- 27563031 TI - The birth of the DS lineshape. PMID- 27563032 TI - Complete Genome Sequence of Pseudomonas aeruginosa Phage AAT-1. AB - Aspects of the interaction between phages and animals are of interest and importance for medical applications. Here, we report the genome sequence of the lytic Pseudomonas phage AAT-1, isolated from mammalian serum. AAT-1 is a double stranded DNA phage, with a genome of 57,599 bp, containing 76 predicted open reading frames. PMID- 27563034 TI - Isolating Viable Ancient Bacteria: What You Put In Is What You Get Out. PMID- 27563033 TI - Genome Sequence of Jumbo Phage vB_AbaM_ME3 of Acinetobacter baumanni. AB - Bacteriophage (phage) vB_AbaM_ME3 was previously isolated from wastewater effluent using the propagating host Acinetobacter baumannii DSM 30007. The full genome was sequenced, revealing it to be the largest Acinetobacter bacteriophage sequenced to date with a size of 234,900 bp and containing 326 open reading frames (ORFs). PMID- 27563035 TI - Reply to "Isolating Viable Ancient Bacteria: What You Put In Is What You Get Out". PMID- 27563036 TI - Draft Genome Sequences of Acinetobacter baumannii Isolates from Wounded Military Personnel. AB - Acinetobacter baumannii is a Gram-negative bacterium capable of causing hospital acquired infections that has been grouped with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as ESKAPE pathogens because of their extensive drug resistance phenotypes and increasing risk to human health. Twenty-four multidrug-resistant A. baumannii strains isolated from wounded military personnel were sequenced and annotated. PMID- 27563037 TI - Complete Genome Sequence of Foot-and-Mouth Disease Virus Serotype SAT3 Zimbabwe/4/81. AB - The complete genome sequence of a foot-and-mouth disease (FMD) serotype SAT3 virus ZIM/4/81, which belongs to a topotype 1 (SEZ), is reported here. PMID- 27563038 TI - Draft Genome Sequence of Lactobacillus reuteri Strain CRL 1098, an Interesting Candidate for Functional Food Development. AB - We report here the draft genome sequence of Lactobacillus reuteri strain CRL 1098. This strain represents an interesting candidate for functional food development because of its proven probiotic properties. The draft genome sequence is composed of 1,969,471 bp assembled into 45 contigs and an average G+C content of 38.8%. PMID- 27563039 TI - Complete Genome Sequence of Neisseria weaveri Strain NCTC13585. AB - Neisseria weaveri is a commensal organism of the canine oral cavity and an occasional opportunistic human pathogen which is associated with dog bite wounds. Here we report the first complete genomic sequence of the N. weaveri NCTC13585 (CCUG30381) strain, which was originally isolated from a patient with a canine bite wound. PMID- 27563040 TI - Complete Genome Sequence of a Cylindrospermopsin-Producing Cyanobacterium, Cylindrospermopsis raciborskii CS505, Containing a Circular Chromosome and a Single Extrachromosomal Element. AB - Cylindrospermopsis raciborskii is a freshwater cyanobacterium producing bloom events and toxicity in drinking water source reservoirs. We present the first genome sequence for C. raciborskii CS505 (Australia), containing one 4.1-Mbp chromosome and one 110-Kbp plasmid having G+C contents of 40.3% (3933 genes) and 39.3% (111 genes), respectively. PMID- 27563041 TI - Multiple Genome Sequences of the Important Beer-Spoiling Species Lactobacillus backii. AB - Lactobacillus backii is an important beer-spoiling species. Five strains isolated from four different breweries were sequenced using single-molecule real-time sequencing. Five complete genomes were generated, which will help to understand niche adaptation to beer and provide the basis for consecutive analyses. PMID- 27563042 TI - Draft Genome Sequence of the Aureocin A53-Producing Strain Staphylococcus aureus A53. AB - Here, we present the 2,658,363-bp draft genome sequence of the aureocin A53 producing strain Staphylococcus aureus A53. This genome information may contribute to the optimal and rational exploitation of aureocin A53 as an antimicrobial agent and to its production in large scale. PMID- 27563043 TI - Draft Genome Sequences of Two Bacillus anthracis Strains from Etosha National Park, Namibia. AB - Bacillus anthracis strains K1 and K2 were isolated from two plains zebra anthrax carcasses in Etosha National Park, Namibia. These are draft genomes obtained by Illumina MiSeq sequencing of isolates collected from culture of blood-soaked soil from each carcass. PMID- 27563044 TI - Complete Genome Sequences of the Historical Legionella pneumophila Strains OLDA and Pontiac. AB - Here, we report the complete genome sequences of Legionella pneumophila serogroup 1 strains OLDA and Pontiac, which predate the 1976 Philadelphia Legionnaires' disease outbreak. Strain OLDA was isolated in 1947 from an apparent sporadic case, and strain Pontiac caused an explosive outbreak at a Michigan health department in 1968. PMID- 27563045 TI - Draft Genome Sequences of Pseudoalteromonas telluritireducens DSM 16098 and P. spiralis DSM 16099 Isolated from the Hydrothermal Vents of the Juan de Fuca Ridge. AB - This report describes the draft genome sequences of two strains, Pseudoalteromonas telluritireducens DSM 16098 and P. spiralis DSM 16099, which were isolated from hydrothermal vents of the Juan de Fuca Ridge. The reads generated by an Ion Torrent PGM were assembled into contigs with total sizes of 4.4 Mb and 4.1 Mb for DSM 16098 and DSM 16099, respectively. PMID- 27563046 TI - Draft Genome Sequence of Alcanivorax sp. Strain KX64203 Isolated from Deep-Sea Sediments of Iheya North, Okinawa Trough. AB - This report describes the draft genome sequence of Alcanivorax sp. strain KX64203, isolated from deep-sea sediment samples. The reads generated by an Ion Torrent PGM were assembled into contigs, with a total size of 4.76 Mb. The data will improve our understanding of the strain's function in alkane degradation. PMID- 27563047 TI - Complete Genome Sequence of Streptomyces parvulus 2297, Integrating Site Specifically with Actinophage R4. AB - Streptomyces parvulus 2297, which is a host for site-specific recombination according to actinophage R4, is derived from the type strain ATCC 12434. Species of S. parvulus are known as producers of polypeptide antibiotic actinomycins and have been considered for industrial applications. We herein report for the first time the complete genome sequence of S. parvulus 2297. PMID- 27563048 TI - First Complete Genome Sequence of a Chikungunya Virus Strain Isolated from a Patient Diagnosed with Dengue Virus Infection in Malaysia. AB - Here, we report the complete genome sequence of a chikungunya virus coinfection strain isolated from a dengue virus serotype 2-infected patient in Malaysia. This coinfection strain was determined to be of the Asian genotype and contains a novel insertion in the nsP3 gene. PMID- 27563049 TI - Genome Sequence of a Lactococcus lactis Strain Isolated from Salmonid Intestinal Microbiota. AB - Lactococcus lactis is a common inhabitant of the intestinal microbiota of salmonids, especially those in aquaculture systems. Here, we present a genome sequence of a Lactococcus lactis strain isolated from the intestinal contents of rainbow trout reared in Chile. PMID- 27563050 TI - Draft Genome Sequence of Cellulolytic and Xylanolytic Cellulomonas sp. Strain B6 Isolated from Subtropical Forest Soil. AB - Cellulomonas sp. strain B6 was isolated from a subtropical forest soil sample and presented (hemi)cellulose-degrading activity. We report here its draft genome sequence, with an estimated genome size of 4 Mb, a G+C content of 75.1%, and 3,443 predicted protein-coding sequences, 92 of which are glycosyl hydrolases involved in polysaccharide degradation. PMID- 27563051 TI - Genome Sequence of Enterobacter cloacae Strain SENG-6, a Bacterium Producing Histo-Blood Group Antigen-Like Substances That Can Bind with Human Noroviruses. AB - Enterobacter sp. strain SENG-6, isolated from healthy human feces, produces histo blood group antigen (HBGA)-like substances that can bind with human noroviruses. Based on the genome sequence analysis, strain SENG-6 belongs to the species Enterobacter cloacae The genome sequence of this strain should help identify genes associated with the production of HBGA-like substances. PMID- 27563052 TI - Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution. AB - How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. PMID- 27563055 TI - The Histamine H3 Receptor: Structure, Pharmacology, and Function. AB - Among the four G protein-coupled receptors (H1-H4) identified as mediators of the biologic effects of histamine, the H3 receptor (H3R) is distinguished for its almost exclusive expression in the nervous system and the large variety of isoforms generated by alternative splicing of the corresponding mRNA. Additionally, it exhibits dual functionality as autoreceptor and heteroreceptor, and this enables H3Rs to modulate the histaminergic and other neurotransmitter systems. The cloning of the H3R cDNA in 1999 by Lovenberg et al. allowed for detailed studies of its molecular aspects. In this work, we review the characteristics of the H3R, namely, its structure, constitutive activity, isoforms, signal transduction pathways, regional differences in expression and localization, selective agonists, antagonists and inverse agonists, dimerization with other neurotransmitter receptors, and the main presynaptic and postsynaptic effects resulting from its activation. The H3R has attracted interest as a potential drug target for the treatment of several important neurologic and psychiatric disorders, such as Alzheimer and Parkinson diseases, Gilles de la Tourette syndrome, and addiction. PMID- 27563053 TI - The Roles of Mutation, Selection, and Expression in Determining Relative Rates of Evolution in Mitochondrial versus Nuclear Genomes. AB - Eukaryotes rely on proteins encoded by the nuclear and mitochondrial (mt) genomes, which interact within multisubunit complexes such as oxidative phosphorylation enzymes. Although selection is thought to be less efficient on the asexual mt genome, in bilaterian animals the ratio of nonsynonymous to synonymous substitutions (omega) is lower in mt- compared with nuclear-encoded OXPHOS subunits, suggesting stronger effects of purifying selection in the mt genome. Because high levels of gene expression constrain protein sequence evolution, one proposed resolution to this paradox is that mt genes are expressed more highly than nuclear genes. To test this hypothesis, we investigated expression and sequence evolution of mt and nuclear genes from 84 diverse eukaryotes that vary in mt gene content and mutation rate. We found that the relationship between mt and nuclear omega values varied dramatically across eukaryotes. In contrast, transcript abundance is consistently higher for mt genes than nuclear genes, regardless of which genes happen to be in the mt genome. Consequently, expression levels cannot be responsible for the differences in omega Rather, 84% of the variance in the ratio of omega values between mt and nuclear genes could be explained by differences in mutation rate between the two genomes. We relate these findings to the hypothesis that high rates of mt mutation select for compensatory changes in the nuclear genome. We also propose an explanation for why mt transcripts consistently outnumber their nuclear counterparts, with implications for mitonuclear protein imbalance and aging. PMID- 27563057 TI - Classic Spotlight: Seeing Is Believing-Imaging the Active Bacterial Flagellar Filaments. PMID- 27563056 TI - 3.9 A structure of the nucleosome core particle determined by phase-plate cryo EM. AB - The Volta phase plate is a recently developed electron cryo-microscopy (cryo-EM) device that enables contrast enhancement of biological samples. Here we have evaluated the potential of combining phase-plate imaging and single particle analysis to determine the structure of a small protein-DNA complex. To test the method, we made use of a 200 kDa Nucleosome Core Particle (NCP) reconstituted with 601 DNA for which a high-resolution X-ray crystal structure is known. We find that the phase plate provides a significant contrast enhancement that permits individual NCPs and DNA to be clearly identified in amorphous ice. The refined structure from 26,060 particles has an overall resolution of 3.9 A and the density map exhibits structural features consistent with the estimated resolution, including clear density for amino acid side chains and DNA features such as the phosphate backbone. Our results demonstrate that phase-plate cryo-EM promises to become an important method to determine novel near-atomic resolution structures of small and challenging samples, such as nucleosomes in complex with nucleosome-binding factors. PMID- 27563054 TI - Molecular Determinants of Mutant Phenotypes, Inferred from Saturation Mutagenesis Data. AB - Understanding how mutations affect protein activity and organismal fitness is a major challenge. We used saturation mutagenesis combined with deep sequencing to determine mutational sensitivity scores for 1,664 single-site mutants of the 101 residue Escherichia coli cytotoxin, CcdB at seven different expression levels. Active-site residues could be distinguished from buried ones, based on their differential tolerance to aliphatic and charged amino acid substitutions. At nonactive-site positions, the average mutational tolerance correlated better with depth from the protein surface than with accessibility. Remarkably, similar results were observed for two other small proteins, PDZ domain (PSD95pdz3) and IgG-binding domain of protein G (GB1). Mutational sensitivity data obtained with CcdB were used to derive a procedure for predicting functional effects of mutations. Results compared favorably with those of two widely used computational predictors. In vitro characterization of 80 single, nonactive-site mutants of CcdB showed that activity in vivo correlates moderately with thermal stability and solubility. The inability to refold reversibly, as well as a decreased folding rate in vitro, is associated with decreased activity in vivo. Upon probing the effect of modulating expression of various proteases and chaperones on mutant phenotypes, most deleterious mutants showed an increased in vivo activity and solubility only upon over-expression of either Trigger factor or SecB ATP-independent chaperones. Collectively, these data suggest that folding kinetics rather than protein stability is the primary determinant of activity in vivo This study enhances our understanding of how mutations affect phenotype, as well as the ability to predict fitness effects of point mutations. PMID- 27563058 TI - Classic Spotlight: Putting Things in Order-Matching Genes to Flagellar Motor Images. PMID- 27563061 TI - Impact of Domestic Violence on Children's Education in Colombia: Methodological Challenges. AB - We explore the methodological challenges of estimating the effects of intimate partner violence (IPV) against the mother on the educational outcomes of her children. We tackle the problem of potential endogeneity and non-random selection of children into situations where they are exposed to IPV using non-parametric matching methods and parametric instrumental variable methods. Using Colombia's 2005 Demographic and Health Survey (DHS), we find that IV and non-IV estimators produce qualitatively similar results at varying degrees of precision, for some educational outcomes. Therefore, exogeneity of IPV to various education outcomes cannot be taken for granted; appropriate methods need to be used to study its causal effects. PMID- 27563062 TI - "Till Death Us Do Part": Homicide Defenses for Women in Abusive Relationships Similar Problems-Different Responses in Germany and Australia. AB - Cases in which women have killed their sleeping or otherwise inattentive abusive partners to "escape" domestic violence have arisen in both Germany and Australia. In this context, the availability of defenses including provocation and self defense for abused defendants is controversially debated due to their traditional application and interpretation. It appears that these cases have driven law reform and changed judicial interpretation of defenses to some degree in Australia, whereas the situation in Germany remains stagnant. This article argues that while the situation in Australia is not without criticism, the recent legislative developments aimed at affording abused defendants greater access to defenses could serve as food for legal thought in the German debate. PMID- 27563063 TI - Regulation of Amyloid beta Oligomer Binding to Neurons and Neurotoxicity by the Prion Protein-mGluR5 Complex. AB - The prion protein (PrPC) has been suggested to operate as a scaffold/receptor protein in neurons, participating in both physiological and pathological associated events. PrPC, laminin, and metabotropic glutamate receptor 5 (mGluR5) form a protein complex on the plasma membrane that can trigger signaling pathways involved in neuronal differentiation. PrPC and mGluR5 are co-receptors also for beta-amyloid oligomers (AbetaOs) and have been shown to modulate toxicity and neuronal death in Alzheimer's disease. In the present work, we addressed the potential crosstalk between these two signaling pathways, laminin-PrPC-mGluR5 or AbetaO-PrPC-mGluR5, as well as their interplay. Herein, we demonstrated that an existing complex containing PrPC-mGluR5 has an important role in AbetaO binding and activity in neurons. A peptide mimicking the binding site of laminin onto PrPC (Ln-gamma1) binds to PrPC and induces intracellular Ca2+ increase in neurons via the complex PrPC-mGluR5. Ln-gamma1 promotes internalization of PrPC and mGluR5 and transiently decreases AbetaO biding to neurons; however, the peptide does not impact AbetaO toxicity. Given that mGluR5 is critical for toxic signaling by AbetaOs and in prion diseases, we tested whether mGlur5 knock-out mice would be susceptible to prion infection. Our results show mild, but significant, effects on disease progression, without affecting survival of mice after infection. These results suggest that PrPC-mGluR5 form a functional response unit by which multiple ligands can trigger signaling. We propose that trafficking of PrPC-mGluR5 may modulate signaling intensity by different PrPC ligands. PMID- 27563064 TI - Molecular Architecture of Full-length TRF1 Favors Its Interaction with DNA. AB - Telomeres are specific DNA-protein structures found at both ends of eukaryotic chromosomes that protect the genome from degradation and from being recognized as double-stranded breaks. In vertebrates, telomeres are composed of tandem repeats of the TTAGGG sequence that are bound by a six-subunit complex called shelterin. Molecular mechanisms of telomere functions remain unknown in large part due to lack of structural data on shelterins, shelterin complex, and its interaction with the telomeric DNA repeats. TRF1 is one of the best studied shelterin components; however, the molecular architecture of the full-length protein remains unknown. We have used single-particle electron microscopy to elucidate the structure of TRF1 and its interaction with telomeric DNA sequence. Our results demonstrate that full-length TRF1 presents a molecular architecture that assists its interaction with telometic DNA and at the same time makes TRFH domains accessible to other TRF1 binding partners. Furthermore, our studies suggest hypothetical models on how other proteins as TIN2 and tankyrase contribute to regulate TRF1 function. PMID- 27563066 TI - The Lysosomal Trafficking Transmembrane Protein 106B Is Linked to Cell Death. AB - A common genetic variation in the transmembrane protein 106B (TMEM106B) gene has been suggested to be a risk factor for frontotemporal lobar degeneration (FTLD) with inclusions of transactive response DNA-binding protein-43 (TDP-43) (FTLD TDP), the most common pathological subtype in FTLD. Furthermore, previous studies have shown that TMEM106B levels are up-regulated in the brains of FTLD-TDP patients, although the significance of this finding remains unknown. In this study, we show that the overexpression of TMEM106B and its N-terminal fragments induces cell death, enhances oxidative stress-induced cytotoxicity, and causes the cleavage of TDP-43, which represents TDP-43 pathology, using cell-based models. TMEM106B-induced death is mediated by the caspase-dependent mitochondrial cell death pathways and possibly by the lysosomal cell death pathway. These findings suggest that the up-regulation of TMEM106B may increase the risk of FTLD by directly causing neurotoxicity and a pathological phenotype linked to FTLD TDP. PMID- 27563065 TI - The Polyadenosine RNA-binding Protein, Zinc Finger Cys3His Protein 14 (ZC3H14), Regulates the Pre-mRNA Processing of a Key ATP Synthase Subunit mRNA. AB - Polyadenosine RNA-binding proteins (Pabs) regulate multiple steps in gene expression. This protein family includes the well studied Pabs, PABPN1 and PABPC1, as well as the newly characterized Pab, zinc finger CCCH-type containing protein 14 (ZC3H14). Mutations in ZC3H14 are linked to a form of intellectual disability. To probe the function of ZC3H14, we performed a transcriptome-wide analysis of cells depleted of either ZC3H14 or the control Pab, PABPN1. Depletion of PABPN1 affected ~17% of expressed transcripts, whereas ZC3H14 affected only ~1% of expressed transcripts. To assess the function of ZC3H14 in modulating target mRNAs, we selected the gene encoding the ATP synthase F0 subunit C (ATP5G1) transcript. Knockdown of ZC3H14 significantly reduced ATP5G1 steady state mRNA levels. Consistent with results suggesting that ATP5G1 turnover increases upon depletion of ZC3H14, double knockdown of ZC3H14 and the nonsense mediated decay factor, UPF1, rescues ATP5G1 transcript levels. Furthermore, fractionation reveals an increase in the amount of ATP5G1 pre-mRNA that reaches the cytoplasm when ZC3H14 is depleted and that ZC3H14 binds to ATP5G1 pre-mRNA in the nucleus. These data support a role for ZC3H14 in ensuring proper nuclear processing and retention of ATP5G1 pre-mRNA. Consistent with the observation that ATP5G1 is a rate-limiting component for ATP synthase activity, knockdown of ZC3H14 decreases cellular ATP levels and causes mitochondrial fragmentation. These data suggest that ZC3H14 modulates pre-mRNA processing of select mRNA transcripts and plays a critical role in regulating cellular energy levels, observations that have broad implications for proper neuronal function. PMID- 27563067 TI - Alternative Processing of the Amyloid Precursor Protein Family by Rhomboid Protease RHBDL4. AB - The amyloid precursor protein (APP) is an ubiquitously expressed cell surface protein and a key molecule in the etiology of Alzheimer disease. Amyloidogenic processing of APP through secretases leads to the generation of toxic amyloid beta (Abeta) peptides, which are regarded as the molecular cause of the disease. We report here an alternative processing pathway of APP through the mammalian intramembrane rhomboid protease RHBDL4. RHBDL4 efficiently cleaves APP inside the cell, thus bypassing APP from amyloidogenic processing, leading to reduced Abeta levels. RHBDL4 cleaves APP multiple times in the ectodomain, resulting in several N- and C-terminal fragments that are not further degraded by classical APP secretases. Knockdown of endogenous RHBDL4 results in decreased levels of C terminal fragments derived from endogenous APP. Similarly, we found the APP family members APLP1 and APLP2 to be substrates of RHBDL4. We conclude that RHBDL4-mediated APP processing provides insight into APP and rhomboid physiology and qualifies for further investigations to elaborate its impact on Alzheimer disease pathology. PMID- 27563069 TI - An Evaluation of the Honey Bee (Hymenoptera: Apidae) Safety Profile of a New Systemic Insecticide, Flupyradifurone, Under Field Conditions in Florida. AB - Flupyradifurone (Sivanto) is a novel systemic insecticide from the butenolide class developed by Bayer. Based on available data (USEPA 2014), this insecticide appears to have a favorable safety profile for honey bee colonies. As a result, the label permits the product to be applied during prebloom and bloom in various crops, including citrus, except when mixed with azole fungicides during the blooming period. We placed 24 honey bee (Apis mellifera L.) colonies adjacent to eight flowering buckwheat (Fagopyrum esculentum Moench) fields that either had been sprayed with the maximum label rate of flupyradifurone or with water only (control fields), with three colonies placed adjacent to each field. We conducted colony strength assessments during which the number of adult bees, eggs, uncapped brood cells, capped brood cells, food storage cells, and weights of honey supers and brood chambers were determined prior to, during, and after the flowering period. We also analyzed bee-collected pollen and nectar for flupyradifurone residues. Overall, there were no differences in any colony strength parameter for colonies placed at control and flupyradifurone-treated buckwheat fields. Residue analyses showed that pollen (x = 565.8 ppb) and nectar (x = 259.4 ppb) gathered by bees on fields treated with flupyradifurone contained significantly higher flupyradifurone residues than did bee bread and unprocessed nectar collected by bees from control fields (75% of samples 120 mg/L after delivery) 6 months (p = 0.02) and 12 months postpartum (p < 0.0001) compared to controls. Also reduced GFR (glomerular filtration rate) persisted up to 6 months postpartum in PE patients compared to controls (p < 0.001). Prepartum sFlt-1 levels indeed correlated with impaired renal function parameters. Conclusion. A significant proportion of our PE patients had lower GFR levels and persistent proteinuria up to 12 months postpartum. Prepartum sFlt-1 is a trend-setting marker for impaired renal function postpartum, but it is not sufficient enough to predict renal impairment after PE. An evaluation of 24-month follow-up data is scheduled. PMID- 27563164 TI - Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus. AB - Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus. PMID- 27563167 TI - Contrasting species and functional beta diversity in montane ant assemblages. AB - AIM: Beta diversity describes the variation in species composition between sites and can be used to infer why different species occupy different parts of the globe. It can be viewed in a number of ways. First, it can be partitioned into two distinct patterns: turnover and nestedness. Second, it can be investigated from either a species identity or a functional-trait point of view. We aim to document for the first time how these two aspects of beta diversity vary in response to a large environmental gradient. LOCATION: Maloti-Drakensberg Mountains, southern Africa. METHODS: We sampled ant assemblages along an extensive elevational gradient (900-3000 m a.s.l.) twice yearly for 7 years, and collected functional-trait information related to the species' dietary and habitat-structure preferences. We used recently developed methods to partition species and functional beta diversity into their turnover and nestedness components. A series of null models were used to test whether the observed beta diversity patterns differed from random expectations. RESULTS: Species beta diversity was driven by turnover, but functional beta diversity was composed of both turnover and nestedness patterns at different parts of the gradient. Null models revealed that deterministic processes were likely to be responsible for the species patterns but that the functional changes were indistinguishable from stochasticity. MAIN CONCLUSIONS: Different ant species are found with increasing elevation, but they tend to represent an increasingly nested subset of the available functional strategies. This finding is unique and narrows down the list of possible factors that control ant existence across elevation. We conclude that diet and habitat preferences have little role in structuring ant assemblages in montane environments and that some other factor must be driving the non-random patterns of species turnover. This finding also highlights the importance of distinguishing between different kinds of beta diversity. PMID- 27563166 TI - Elevated Plasma alpha-Defensins (HNP1-3) Levels Correlated with IgA1 Glycosylation and Susceptibility to IgA Nephropathy. AB - Aim. IgA nephropathy (IgAN) is the most common form of glomerulonephritis. Recent genome-wide association study (GWAS) suggested that DEFA locus (which encodes alpha-defensins) may play a key role in IgAN. Methods. The levels of alpha defensins in 169 IgAN patients and 83 healthy controls were tested by ELISA. Results. We observed that alpha-defensins human neutrophil peptides 1-3 (HNP1-3) in IgAN patients were elevated compared with healthy controls. The mean levels of alpha-defensins of 83 healthy controls and 169 IgAN patients were 50 ng/mL and 78.42 ng/mL. When the results were adjusted to the mean levels of alpha-defensins of IgAN patients, the percentage of individuals with high levels of alpha defensins increased in IgAN patients (22.5%) compared to healthy controls (9.6%) (p = 0.013). The elevation of alpha-defensins in IgAN patients was independent of renal function or neutrophil count, which were major sources of alpha-defensins in circulation. More importantly, negative correlation was observed between galactose-deficient IgA1and alpha-defensins. Conclusion. As alpha-defensin is a lectin-like peptide, we speculated that it might be involved in IgA galactose deficiency. The data implied that patients with IgAN had higher plasma alpha defensins levels and high alpha-defensins correlated with IgA galactose deficiency, further suggesting a pathogenic role of alpha-defensins in IgAN. PMID- 27563168 TI - Mapping Viscoelastic and Plastic Properties of Polymers and Polymer-Nanotube Composites using Instrumented Indentation. AB - An instrumented indentation method is developed for generating maps of time dependent viscoelastic and time-independent plastic properties of polymeric materials. The method is based on a pyramidal indentation model consisting of two quadratic viscoelastic Kelvin-like elements and a quadratic plastic element in series. Closed-form solutions for indentation displacement under constant load and constant loading-rate are developed and used to determine and validate material properties. Model parameters are determined by point measurements on common monolithic polymers. Mapping is demonstrated on an epoxy-ceramic interface and on two composite materials consisting of epoxy matrices containing multi-wall carbon nanotubes. A fast viscoelastic deformation process in the epoxy was unaffected by the inclusion of the nanotubes, whereas a slow viscoelastic process was significantly impeded, as was the plastic deformation. Mapping revealed considerable spatial heterogeneity in the slow viscoelastic and plastic responses in the composites, particularly in the material with a greater fraction of nanotubes. PMID- 27563169 TI - Effective Partnership is an underpinning of ANSI/ASSE Z88.2-2015 Practices for Respiratory Protection. AB - In the U.S., respiratory protection is broadly supported by a system of coordinated efforts among governmental organizations, professional associations, researchers, industrial hygienists, manufacturers, and others who produce knowledge, best practice guidance, standards, regulations, technologies, and products to assure workers can be effectively protected. Ultimately, the work of these partners is applied by employers in establishing and implementing an effective ANSI/ASSE Z88.2-2015 conforming respirator program. This article describes key partners and their activities and/or responsibilities to assure an effective respirator program. PMID- 27563171 TI - Polymer-Free Films of Inorganic Halide Perovskite Nanocrystals as UV-to-White Color-Conversion Layers in LEDs. PMID- 27563170 TI - QM/MM free energy simulations: recent progress and challenges. AB - Due to the higher computational cost relative to pure molecular mechanical (MM) simulations, hybrid quantum mechanical/molecular mechanical (QM/MM) free energy simulations particularly require a careful consideration of balancing computational cost and accuracy. Here we review several recent developments in free energy methods most relevant to QM/MM simulations and discuss several topics motivated by these developments using simple but informative examples that involve processes in water. For chemical reactions, we highlight the value of invoking enhanced sampling technique (e.g., replica-exchange) in umbrella sampling calculations and the value of including collective environmental variables (e.g., hydration level) in metadynamics simulations; we also illustrate the sensitivity of string calculations, especially free energy along the path, to various parameters in the computation. Alchemical free energy simulations with a specific thermodynamic cycle are used to probe the effect of including the first solvation shell into the QM region when computing solvation free energies. For cases where high-level QM/MM potential functions are needed, we analyze two different approaches: the QM/MM-MFEP method of Yang and co-workers and perturbative correction to low-level QM/MM free energy results. For the examples analyzed here, both approaches seem productive although care needs to be exercised when analyzing the perturbative corrections. PMID- 27563172 TI - Negative Impact of Hypoxia on Tryptophan 2,3-Dioxygenase Function. AB - Tryptophan is an essential amino acid for hosts and pathogens. The liver enzyme tryptophan 2,3-dioxygenase (TDO) provokes, by its ability to degrade tryptophan to N-formylkynurenine, the precursor of the immune-relevant kynurenines, direct and indirect antimicrobial and immunoregulatory states. Up to now these TDO mediated broad-spectrum effector functions have never been observed under hypoxia in vitro, although physiologic oxygen concentrations in liver tissue are low, especially in case of infection. Here we analysed recombinant expressed human TDO and ex vivo murine TDO functions under different oxygen conditions and show that TDO-induced restrictions of clinically relevant pathogens (bacteria, parasites) and of T cell proliferation are abrogated under hypoxic conditions. We pinpointed the loss of TDO efficiency to the reduction of TDO activity, since cell survival and TDO protein levels were unaffected. In conclusion, the potent antimicrobial as well as immunoregulatory effects of TDO were substantially impaired under hypoxic conditions that pathophysiologically occur in vivo. This might be detrimental for the appropriate host immune response towards relevant pathogens. PMID- 27563173 TI - TLR2-Dependent Signaling for IL-15 Production Is Essential for the Homeostasis of Intestinal Intraepithelial Lymphocytes. AB - TLR2 signaling is related to colitis and involved in regulation of innate immunity in the intestinal tract, but the mechanisms remain unclear. The aim of this study is to investigate how TLR2 affects differentiation of intraepithelial lymphocytes (IELs) and regulates the susceptibility of colitis. IELs were isolated from the small intestine and colon of mice, respectively. The IEL phenotype, activation, and apoptosis were examined using flow cytometry and RT PCR. IL-15 expression and IEL location were detected through immunohistochemistry. The experimental colitis was induced by administration of dextran sulfate sodium (DSS). We found that the numbers of CD8alphaalpha (+), CD8alphabeta (+), and TCRgammadelta (+) IELs were significantly decreased in TLR2 deficient mice and the residual IELs displayed reduced activation and proliferation and increased apoptosis, accompanied with impaired IL-15 expression by intestinal epithelial cells (IECs). Further study showed that TLR2 signaling maintained the expression of IL-15 in IEC via NF-kappaB activation. Moreover, TLR2-deficient mice were found to be more susceptible to DSS-induced colitis as shown by the increased severity of colitis. Our results demonstrate that IECs contribute to the maintenance of IELs at least partly via TLR2-dependent IL-15 production, which provides a clue that may link IECs to innate immune protection of the host via IELs. PMID- 27563174 TI - Interplay between Oxidative Stress and Inflammation in Cardiometabolic Syndrome. PMID- 27563175 TI - Comparative evaluation of the efficacy of two modes of delivery of Piroxicam (Dolonex((r))) for the management of postendodontic pain: A randomized control trial. AB - BACKGROUND: Alleviating pain is of utmost importance when treating patients with endodontic pain. AIM: To compare and evaluate the efficacy of two modes of delivery of pretreatment Piroxicam (Dolonex((r)), Pfizer) for the management of postendodontic pain. MATERIALS AND METHODS: Sixty-six patients with symptomatic irreversible pulpitis were randomly divided into three groups of 22 subjects Group I - control group, no pharmacological intervention, Group II - patients received pretreatment oral Piroxicam (40 mg), Group III - patients received pretreatment intraligamentary injections totaling 0.4 mL of Piroxicam. Single visit endodontic therapy was performed by a single endodontist. Visual analogue scale was used to record pain before treatment and 4, 8, 12, 24, and 48 h postoperatively. Mann-Whitney U-test and Kruskal-Wallis tests were used to analyze the data. RESULTS: The patients in Groups II and III perceived less postendodontic pain as compared to Group I (P < 0.05), at all the time intervals. At 12, 24, and 48 h, pain experience in patients of Group III was significantly less. CONCLUSIONS: Intraligamentary mode of delivery of Piroxicam was more efficacious. PMID- 27563176 TI - Two-year clinical evaluation of resin composite in posterior teeth: A randomized controlled study. AB - BACKGROUND: Clinical evaluations as fundamental method to prove the efficiency of restorative materials. AIM: This study evaluated the clinical performance of restorative systems during 2 years of clinical service. MATERIALS AND METHODS: This study assessed the clinical performance of restorative systems (Filtek Z250 and P60), during 2 years of clinical service, using the US Public Health Service system. The randomized and double-blind study comprising thirty volunteers. The restorations were evaluated at baseline, 6, 12, and 24 months. It was used the following criteria: marginal discoloration (MD), marginal integrity (MI), superficial texture (ST), wear (W), postoperative sensitivity (PS) and recurrent caries (RC). RESULTS: Statistic analysis was performed using Fisher's and McNemar's exact tests and Pearsons's Chi-square in a significance level of 5%. The results at baseline and 24 months for Group I were: MD - 100, 100%; MI - 100, 88.6%; ST - 100, 94.3%; W - 100, 94.3%; PS - 100, 100%; RC - 100, 100%, of alpha scores; Group II: MD - 100, 97.1%; MI - 100, 91.4%; ST - 100, 94.3%; W - 100, 91.4%; PS - 100, 100%; RC - 100, 100%, of alpha scores. It was observed no statistical difference in the evaluated criteria and period. CONCLUSIONS: After 24 months of evaluation, both restorative systems exhibited acceptable clinical performance. PMID- 27563177 TI - Influence of three Ni-Ti cleaning and shaping files on postinstrumentation endodontic pain: A triple-blinded, randomized, controlled trial. AB - AIM: This randomized, controlled trial evaluated the incidence of postinstrumentation pain on using two different rotary Ni-Ti and one reciprocating Ni-Ti cleaning and shaping systems. MATERIALS AND METHODS: Asfter sample size estimation, a total of 152 patients were randomized to three groups (Group WO [WaveOne], Group PU [ProTaper Universal], and Group Mt [Mtwo]). Selection of patients was based on root curvature, periapical lesion, vitality, gender, and diagnosis of the patient. A similar clinical protocol was followed and endodontic treatment was performed. Pre- and post-instrumentation pain scores (2, 4, 6, 8, 12, 36, and 48 h) were recorded using visual analog scale score. Kruskal-Wallis test was done for overall comparison of the groups. Bonferroni corrected Mann-Whitney test was done for pair-wise comparisons and Friedman test was done to compare pain between time points in each file system (P < 0.05). RESULTS: All preinstrumentation pain values were higher than postinstrumentation pain values (P < 0.05). At 48 h, patients in Group WO experienced more pain compared to the other two groups. Pain scores of nonvital teeth were significantly higher when compared to vital teeth. Among nonvital teeth, patients in Group WO had early onset of pain at 6 h and lasted till 48 h, whereas pain started at 12 h and lasted till 36 and 48 h for Group Mt and Group PU, respectively. CONCLUSION: Patients treated with WaveOne files experienced more pain when compared to the other files. Nonvital teeth experienced more pain compared to vital teeth. Group Mt had the lowest postinstrumentation pain. PMID- 27563178 TI - Expansion of Gutta-percha in contact with various concentrations of zinc oxide eugenol sealer: A three-dimensional volumetric study using spiral computed tomography. AB - AIM: The purpose of this study was to evaluate the three-dimensional expansion of Gutta-percha (GP), at various powder/liquid ratios, of a zinc oxide-eugenol (ZOE) based sealer using spiral computed tomography (SCT). MATERIALS AND METHODS: Thirty-five freshly extracted human mandibular premolars were selected for this study. Cleaning and shaping were performed in all the teeth initially with hand K files up to #25 and finally with RaCe rotary instruments (25/06). Teeth were randomly divided into five groups of 7 teeth each. Specimens were scanned using SCT. They were then viewed both cross-sectionally and longitudinally, with a constant thickness of 1 mm/slice. The volume of root canal in each tooth was estimated. Obturation was performed by GP points (25/04) and ZOE-based root canal sealer in all groups with different powder-liquid ratio. Groups 1, 2, 3, and 4, had powder/liquid ratio of 1:1, 1:2, 1:3, and 1:4, respectively, while in the control group, no sealer was used. The obturation was performed by sealer coated single cone GP. A second SCT scan was performed to determine the volume of GP and sealer in all four groups 1 day after obturation. The third and fourth SCT scans were taken 7 and 30 days after obturation, respectively. The mean volume of GP per group was calculated. Data were statistically analyzed using one-way ANOVA. Inter-group comparisons were done using Scheffe post hoc multiple comparisons test. RESULTS: All groups with sealer showed expansion of GP at both 7(th) day and 30(th) day, which was statistically significant from the GP volume at 1(st) day. Groups 2 and 3 with powder/liquid ratio of 1:2 and 1:3 gave the highest mean volume values during 30 days period and showed significant expansion in comparison with Groups 1 and 4 with powder/liquid ratio of 1:1 and 1:4, respectively. CONCLUSION: Increasing the ratio of eugenol in sealer resulted in the volumetric expansion of GP. However, further studies should be performed to confirm the expansion of GP, leading to the achievement of fluid impervious seal. PMID- 27563179 TI - Effectiveness of conventional syringe irrigation, vibringe, and passive ultrasonic irrigation performed with different irrigation regimes in removing triple antibiotic paste from simulated root canal irregularities. AB - BACKGROUND: This study evaluated the efficacy of a sonic device (Vibringe), passive ultrasonic irrigation (PUI), and conventional syringe irrigation (CSI) in the removal of triple antibiotic paste (TAP) from artificial standardized grooves in the apical and coronal thirds of a root canal. MATERIALS AND METHODS: One hundred eighteen root canals were prepared using the ProTaper system. The roots were split longitudinally, and a standardized groove was prepared in the apical and coronal parts of one segment. The grooves were filled with TAP, and the roots were reassembled. The roots were randomly divided into nine experimental groups and two control groups, according to the following irrigation methods: (1) CSI with sodium hypochlorite (NaOCl) + ethylenediaminetetraacetic acid (EDTA), (2) CSI/EDTA, (3) CSI/NaOCl, (4) PUI/NaOCl + EDTA, (5) PUI/EDTA, (6) PUI/NaOCl, (7) Vibringe/NaOCl + EDTA, (8) Vibringe/EDTA, and (9) Vibringe/NaOCl. The amount of remaining medicament was evaluated under a stereomicroscope. RESULTS: In the apical third, Vibringe/NaOCl + EDTA and PUI/NaOCl + EDTA were superior to the other groups (P < 0.05); there was no significant difference between the other experimental groups (P > 0.05). In the coronal third, there was no significant difference between the experimental groups (P > 0.05). CONCLUSIONS: The use of the NaOCl/EDTA combination together with sonic or ultrasonic agitation improved the removal of TAP from the apical third. PMID- 27563180 TI - In vitro evaluation of remineralization efficacy of different calcium- and fluoride-based delivery systems on artificially demineralized enamel surface. AB - BACKGROUND: Caries is the most common dental disease facing the world population. Caries can be prevented by remineralizing early enamel lesions. AIM: To evaluate remineralization efficacy of stannous fluoride (SnF2), casein phosphopeptide amorphous calcium phosphate with fluoride (CPP-ACPF) and calcium sucrose phosphate (CaSP). MATERIALS AND METHODS: Fifty enamel samples were taken; they were divided into five groups (n = 10). Demineralization was carried out with Groups A, B, C, and E. Remineralization was carried out with Groups A, B, and C for 7 days using SnF2, CPP-ACPF, and CaSP, respectively. In Group D, no surface treatment was carried out, to mark as positive control whereas Group E was kept as negative control with only surface demineralization of enamel. Enamel microhardness was tested using Vickers's microhardness tester after 7 day remineralization regime. STATISTICAL ANALYSIS: One-way analysis of variance and post hoc Tukey tests were performed. RESULTS: The mean microhardness values in descending order: Positive control > SnF2> CaSP > CPP-ACPF > negative control. CONCLUSION: All remineralizing agents showed improved surface remineralization. However, complete remineralization did not occur within 7 days. SnF2 showed the highest potential for remineralization followed by CaSP and CPP-ACPF. PMID- 27563181 TI - The effectiveness of eucalyptus oil, orange oil, and xylene in dissolving different endodontic sealers. AB - OBJECTIVE: The objective of this study was to evaluate the dissolution effectiveness of eucalyptus oil, orange oil, xylene, and distilled water on three different endodontic sealers. MATERIALS AND METHODS: About 240 samples of root canal sealers (eighty for each sealer) were prepared and divided into four groups of 20 each for immersion in different organic solvents. Each group was further subdivided into two subgroups (n = 10) for 2 and 10 min of immersion time. The mean percentage of weight loss was determined for each sealer in each solvent at both time periods. Data were statistically analyzed by two factor analysis of variance and significance of mean difference was obtained by Tukey's post hoc test (P < 0.05). RESULTS: The lowest level of solubility was observed for Adseal followed by Apexit Plus and Endomethasone N at both time periods in all solvents. Apexit Plus showed no significant (P > 0.05) difference in its dissolution in all the organic solvents except distilled water at both the time periods. The solubility profile of Endomethasone N and Adseal did not differ significantly among eucalyptus oil, orange oil, and xylene at 2 min and between eucalyptus oil and orange oil at 10 min. However, at 10 min, Endomethasone N and Adseal showed a more pronounced solubility in xylene as compared to both eucalyptus oil and orange oil. CONCLUSIONS: In general, xylene was the most effective in dissolving root canal sealers than other organic solvents. Essential oils (eucalyptus oil and orange oil) were found similar in their ability to dissolve Apexit Plus and Endomethasone N. PMID- 27563182 TI - Effects of thermal fatigue on shear punch strength of tooth-colored restoratives. AB - AIMS: This study investigated the effect of thermal fatigue on the shear strength of a range of tooth-colored restorative materials including giomers, zirconia reinforced glass ionomer cement (GIC), nano-particle resin-modified GIC, highly viscous GICs, and composite resin. MATERIALS AND METHODS: Twenty specimens of each material were fabricated in standardized washers (17 mm outer diameter, 9 mm internal diameter, 1 mm thick). The specimens were cured, stored in 100% humidity at 37.5 degrees C for 24 h, and randomly divided into two groups of 10. Group A specimens were nonthermocycled (NT) and stored in distilled water at 37 degrees C for 168 h. Group B specimens were thermocycled (TC) for 10,000 cycles (168 h) with baths X, Y, and Z adjusted to 35 degrees C, 15 degrees C, and 45 degrees C, respectively. Each cycle had dwell times of 28 s in X, and 2s in Y/Z in the order XYXZ. Specimens then underwent shear punch testing at a crosshead speed of 0.5 mm/min with a 2 kN load cell. Statistical analysis of shear strength was done using t-test and two-way ANOVA/Scheffe's post hoc test at significance level P < 0.05. RESULTS: The effect of thermal fatigue on shear strength was material dependent. Except for the "sculptable" giomer (Beautifil II) and a highly viscous GIC (Fuji IX GP Fast), no significant differences in shear strength were generally observed between the NT and TC groups. For both groups, the composite resin (Filtek Z250XT) had the highest shear strength while the zirconia reinforced (zirconomer) and a highly viscous GIC (Ketac Molar Quick) had the lowest. CONCLUSIONS: The effect of thermocycling on shear strength was material dependent. Thermal fatigue, however, did not significantly influence the shear strength of most materials assessed. The "sculptable" composite and giomer were significantly stronger than the other materials evaluated. Shear strength of the "flowable" injectable hybrid giomer was intermediate between the composite and GICs. PMID- 27563183 TI - A systematic review of randomized controlled trials on sterilization methods of extracted human teeth. AB - AIM OF THIS STUDY: The aim was to evaluate the efficiency of different sterilization methods on extracted human teeth (EHT) by a systematic review of in vitro randomized controlled trials. METHODOLOGY: An extensive electronic database literature search concerning the sterilization of EHT was conducted. The search terms used were "human teeth, sterilization, disinfection, randomized controlled trials, and infection control." Randomized controlled trials which aim at comparing the efficiency of different methods of sterilization of EHT were all included in this systematic review. RESULTS: Out of 1618 articles obtained, eight articles were selected for this systematic review. The sterilization methods reviewed were autoclaving, 10% formalin, 5.25% sodium hypochlorite, 3% hydrogen peroxide, 2% glutaraldehyde, 0.1% thymol, and boiling to 100 degrees C. Data were extracted from the selected individual studies and their findings were summarized. CONCLUSION: Autoclaving and 10% formalin can be considered as 100% efficient and reliable methods. While the use of 5.25% sodium hypochlorite, 3% hydrogen peroxide, 2% glutaraldehyde, 0.1% thymol, and boiling to 100 degrees C was inefficient and unreliable methods of sterilization of EHT. PMID- 27563184 TI - Dental unit waterlines disinfection using hypochlorous acid-based disinfectant. AB - OBJECTIVE: The purpose of the study was to investigate the efficacy of a new disinfectant to disinfect the dental unit waterlines. MATERIALS AND METHODS: New dental unit waterlines were installed in 13 dental chairs, and biofilm was allowed to grow for 10 days. Disinfection treatment procedure was carried out in the 12 units, and one unit was left untreated. The dental unit waterlines were removed and analyzed using the scanning electron microscope (SEM) (TESCAN VEGA3 SBU). RESULT: On examination, SEM images showed that there was no slime layer or bacterial cells seen in any of the 12 cut sections obtained from the treated dental waterlines which mean that there was no evident of biofilm formation. Untreated dental unit waterlines showed a microbial colonization with continuous filamentous organic matrix. There was significant biofilm formation in the control tube relative to the samples. CONCLUSION: The tested disinfectant was found to be effective in the removal of biofilm from the dental unit waterlines. PMID- 27563185 TI - Comparison of the amount of apical debris extrusion associated with different retreatment systems and supplementary file application during retreatment process. AB - BACKGROUND: The type of instrument affects the amount of debris extruded. The aim of this study was to compare the effect of retreatment systems and supplementary file application on the amount of apical debris extrusion. MATERIALS AND METHODS: Forty-eight extracted mandibular premolars with a single canal and similar length were selected. The root canals were prepared with the ProTaper Universal system with a torque-controlled engine. The root canals were dried and were obturated using Gutta-percha and sealer. The specimens were randomly divided into four equal groups according to the retreatment procedures (Group 1, Mtwo retreatment files; Group 2, Mtwo retreatment files + Mtwo rotary file #30 supplementary file; Group 3, ProTaper Universal retreatment (PTUR) files; and Group 4, PTUR files + ProTaper F3 supplementary file). The extruded debris during instrumentation were collected into preweighed Eppendorf tubes. The amount of apically extruded debris was calculated by subtracting the initial weight of the tube from the final weight. Three consecutive weights were obtained for each tube. RESULTS: No statistically significant difference was found in the amount of apically extruded debris between Groups 1 and 3 (P = 0.590). A significant difference was observed between Groups 1 and 2 (P < 0.05), and between Groups 3 and 4 (P < 0.05). CONCLUSIONS: The use of supplementary file significantly increased the amount of apically extruded debris. PMID- 27563186 TI - Mouthrinses affect color stability of composite. AB - AIM: The aim of this study is to evaluate the effect of alcohol and nonalcohol containing mouth rinses on the color stability of a nanofilled resin composite restorative material. MATERIALS AND METHODS: A total of 120 samples of a nanofilled resin composite material (Tetric N-Ceram, Ivoclar Vivadent AG, FL-9494 Schaan/Liechtenstein) were prepared and immersed in distilled water for 24 h. Baseline color values were recorded using Color Spectrophotometer 3600d (Konica Minolta, Japan). Samples were then randomly distributed into six groups: Group I distilled water (control group), Group II - Listerine, Group III - Eludril, Group IV - Phosflur, Group V - Amflor, and Group VI - Rexidin. The postimmersion color values of the samples were then recorded, respectively. RESULTS: Significant reduction in the mean color value (before and after immersion) was observed in nonalcohol containing mouth rinses (P < 0.001). CONCLUSION: All mouthrinses tested in the present in-vitro study caused a color shift in the nanofilled resin composite restorative material, but the color shift was dependent on the material and the mouthrinse used. Group VI (Rexidin) showed maximum color change. PMID- 27563187 TI - Marginal adaptation of newer root canal sealers to dentin: A SEM study. AB - AIM: This in vitro study evaluated and compared the marginal adaptation of three newer root canal sealers to root dentin. MATERIALS AND METHODS: Thirty freshly extracted human single-rooted teeth with completely formed apices were taken. Teeth were decoronated, and root canals were instrumented. The specimens were randomly divided into three groups (n = 10) based upon the sealer used. Group 1 - teeth were obturated with epoxy resin sealer (MM-Seal). Group 2 - teeth were obturated with mineral trioxide aggregate (MTA) based sealer (MTA Fillapex), Group 3 - teeth were obturated with bioceramic sealer (EndoSequence BC sealer). Later samples were vertically sectioned using hard tissue microtome and marginal adaptation of sealers to root dentin was evaluated under coronal and apical halves using scanning electron microscopy (SEM) and marginal gap values were recorded. RESULTS: The data were statistically analyzed by two-way ANOVA and Tukey's multiple post hoc test. The highest marginal gap was seen in Group 2 (apical-16680.00 nm, coronal-10796 nm) and the lowest marginal gap was observed in Group 1 (apical-599.42 nm, coronal-522.72 nm). Coronal halves showed superior adaptation compared to apical halves in all the groups under SEM. CONCLUSION: Within the limitations of this study epoxy resin-based MM-Seal showed good marginal adaptation than other materials tested. PMID- 27563188 TI - Comparison of fracture resistance of endodontically treated teeth restored with nanohybrid, silorane, and fiber reinforced composite: An in vitro study. AB - BACKGROUND: The present study was undertaken to evaluate the most suitable restorative for badly mutilated endodontically treated teeth. AIMS: To evaluate and compare the fracture resistance of endodontically treated premolars restored with conventional nanohybrid, silorane composite with glass fibers and newer fiber-reinforced composite in mesio-occluso-distal (MOD) cavities. MATERIALS AND METHODS: Sixty extracted human maxillary premolars were selected. Fifteen intact teeth served as positive controls (Group 1). Endodontic therapy was done in the remaining 45 teeth. MOD cavities were prepared in all the teeth with standardized dimensions and were randomly divided into three groups (Group 2 - nanohybrid + glass fibers, Group 3 - silorane + glass fibers, and Group 4 - fiber-reinforced composite). Restorations were done for all groups. Fracture resistance was measured by Instron universal testing machine. STATISTICAL ANALYSIS USED: One-way anova test and Tukey's post hoc test. RESULTS: Highest fracture resistance was shown by intact teeth group followed by fiber-reinforced composite, nanohybrid, and silorane, respectively. Statistically Significant difference was revealed by anova test (P < 0.0001) and Tukey's post hoc test (P < 0.0001). CONCLUSIONS: Among the experimental groups, fiber-reinforced composite showed the highest fracture resistance. Statistically significant difference was observed for all the groups. PMID- 27563189 TI - Ultrasonic versus sonic activation of the final irrigant in root canals instrumented with rotary/reciprocating files: An in-vitro scanning electron microscopy analysis. AB - AIM: To compare the smear layer and debris removal in root canals instrumented with two different kinematic motions after ultrasonic and sonic irrigation activation. MATERIALS AND METHODS: Eighty freshly extracted teeth were selected for the study and randomly divided the samples into two groups (n = 40) for instrumentation with either rotary ProTaper NEXT (PTN) or reciprocating WaveOne (WO) file systems. These (n = 40) were further divided into two groups (n = 20) where the final irrigant was activated using either Ultrasonics (Passive Ultrasonic Irrigation; PUI) or Sonics (EndoActivator; EA). Group 1: PTN + EA; Group 2: PTN + PUI; Group 3: WO + EA; and Group 4: WO + PUI. During instrumentation, a total of 4 ml of 5.25% NaOCl was used for irrigation. The final irrigation protocol included NaOCl and Smear Clear Solution. The samples were processed by scanning electron microscopic examination for debris and smear layer scoring, and statistical analysis was done. RESULTS: The mean debris and smear layer score was less in the group instrumented by PTN with sonic activation of the irrigant. CONCLUSION: A combination of PTN instrumentation with sonic irrigation activation by EA is more effective in debris and smear layer removal in the groups tested. PMID- 27563190 TI - Four cuspal maxillary second premolar with single root and three root canals: Case report. AB - Traditional configuration of maxillary second premolars has been described to have two cusps, one root and one or two root canals. The endodontic literature reports considerable anatomic aberrations in the root canal morphology of maxillary second premolar but the literature available on the variation in cuspal anatomy and its relationship to the root canal anatomy is sparse. The purpose of this clinical report was to describe the root and root canal configuration of a maxillary second premolar with four cusps. PMID- 27563192 TI - A recipe for health: The dental health quotient? PMID- 27563191 TI - Mineral trioxide aggregate apexification: A novel approach. AB - The treatment of choice for necrotic teeth with immature root is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). MTA offers the option of a two-visit apexification procedure so that the fragile tooth can be restored immediately. However, difficulty in placing the material in the wide apical area requires the use of an apical matrix. Materials such as collagen, calcium sulfate, and hydroxyapatite have been used for this purpose. This article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials. PMID- 27563193 TI - Climbing higher. PMID- 27563194 TI - Accuracy and precision of cone beam computed tomography in periodontal defects measurement (systematic review). AB - Systematic review of literature was made to assess the extent of accuracy of cone beam computed tomography (CBCT) as a tool for measurement of alveolar bone loss in periodontal defect. A systematic search of PubMed electronic database and a hand search of open access journals (from 2000 to 2015) yielded abstracts that were potentially relevant. The original articles were then retrieved and their references were hand searched for possible missing articles. Only articles that met the selection criteria were included and criticized. The initial screening revealed 47 potentially relevant articles, of which only 14 have met the selection criteria; their CBCT average measurements error ranged from 0.19 mm to 1.27 mm; however, no valid meta-analysis could be made due to the high heterogeneity between the included studies. Under the limitation of the number and strength of the available studies, we concluded that CBCT provides an assessment of alveolar bone loss in periodontal defect with a minimum reported mean measurements error of 0.19 +/- 0.11 mm and a maximum reported mean measurements error of 1.27 +/- 1.43 mm, and there is no agreement between the studies regarding the direction of the deviation whether over or underestimation. However, we should emphasize that the evidence to this data is not strong. PMID- 27563195 TI - Effects of scaling and root planing on gingival crevicular fluid vascular endothelial growth factor level in chronic periodontitis patients with and without diabetes mellitus: A clinicobiochemical study. AB - AIM: To estimate the gingival crevicular fluid (GCF) level of vascular endothelial growth factor (VEGF) in periodontally healthy controls and chronic periodontitis (CP) patients with and without diabetes mellitus (DM) and also to investigate the effect of scaling and root planing (SRP) on the GCF VEGF level. MATERIALS AND METHODS: One hundred and five patients were divided into three groups: Healthy (Group 1), CP (Group 2), and CP with DM (Group 3). Group 2 and Group 3 patients underwent SRP planning, and the cases were followed for 6 weeks. Periodontal clinical parameters such as plaque index, gingival index, probing pocket depth, and clinical attachment level were recorded at baseline and 6-week posttherapy. GCF samples collected from each patient were quantified for VEGF level using enzyme-linked immunosorbent assay. RESULTS: The mean GCF VEGF level was increased in CP patients with and without DM compared to healthy patients and SRP therapy caused a statistically significant (P < 0.001) reduction in GCF VEGF level. CONCLUSION: VEGF is increased in GCF of CP patients with and without DM and that SRP substantially reduces its level in GCF. PMID- 27563196 TI - Comparison of serum erythropoietin levels in smokers and nonsmokers with periodontitis: A biochemical study. AB - AIMS: This study was carried out to compare serum erythropoietin (Epo) levels in smokers and nonsmokers with periodontitis. MATERIALS AND METHODS: Fifty-one subjects of both sexes (age range: 30-65 years) with chronic periodontitis (CP) participated in this study. Seventeen patients with generalized CP, nonsmokers without anemia were included in Group I (control group), 17 patients with generalized CP, nonsmokers with anemia were included in Group II, and 17 patients who were smokers, having generalized CP were included in Group III. Peripheral blood samples were obtained and assessed for the number of erythrocytes (total red blood cell [TRBC]), hemoglobin (Hb), and Epo levels. STATISTICAL ANALYSIS USED: One-way analysis of variance and Tukey-Kramer multiple comparisons test to assess the statistical difference between groups. RESULTS: Epo levels varied considerably between the 3 groups. Highest values of Epo were seen in Group III with mean Epo value = 42.81 +/- 15, followed by Group II Epo value = 35.21 +/- 10.9, then Group I Epo value = 22.06 +/- 4.19. Smokers in Group III with CP showed more prevalence toward higher values of Hb% (mean Hb = 12.06 +/- 0.84) while there was no statistical difference in the values of TRBC values among the 3 groups (Group I TRBC value = 3.87 +/- 0.38, Group II TRBC value = 4.01 +/- 0.83, and Group III TRBC value = 3.88 +/- 0.45). CONCLUSION: Periodontitis patients were seen to have lower Epo values further strengthening the hypothesis that CP may lead to anemia of chronic disease. In smokers, higher Hb values were seen with higher Epo levels. It indicates that periodontitis individually and along with smoking may affect anemic status of smokers. Thus, Epo levels may be better means to assess anemic status of smokers than relying only on Hb values. PMID- 27563197 TI - Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis. AB - CONTEXT: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. AIM: To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. MATERIALS AND METHODS: Study population included 15 smoker male patients in the age group of 35-55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. STATISTICAL ANALYSIS USED: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. RESULTS: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. CONCLUSION: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy. PMID- 27563198 TI - Estimation of interleukin-18 in the gingival crevicular fluid and serum of Bengali population with periodontal health and disease. AB - CONTEXT: Host's immune response elicits cytokines in response to bacterial challenge. We explore role of one such cytokine interleukin-18 (IL-18) in periodontal health and disease. AIMS: IL-18 is a pro-inflammatory and tumor suppressive cytokine. Dental literatures suggest that IL-18 might have a role to play in the progression from oral health to periodontal disease. Therefore, this study was undertaken to elucidate the level and role of IL-18 in the gingival crevicular fluid (GCF) and serum of individuals with healthy gingiva, chronic gingivitis, chronic periodontitis, and aggressive periodontitis before and after periodontal therapy. SETTINGS AND DESIGN: Eighty individuals chosen for the study were divided into healthy control group (1A), chronic gingivitis (2A), chronic periodontitis (3A), and aggressive periodontitis (4A) with twenty individuals each. Criteria for the division were the subject's gingival index, probing pocket depth, clinical attachment loss, and radiographic evidence of bone loss. MATERIALS AND METHODS: The individuals underwent treatment (scaling in case of Groups 1A and 2A and scaling and root planing followed by flap surgery in Groups 3A and 4A) to form posttreatment Groups 1B, 2B, 3B, and 4B, respectively. Thus, a total of 160 GCF and 160 serum samples were collected and tested by ELISA. STATISTICAL ANALYSIS USED: Intergroup comparison was done by post hoc Tukey's test. RESULTS: The mean IL-18 concentration was greatest in Group 3A (GCF 144.61 pg/MUl, serum 55.12 pg/ml) followed by Group 4A (GCF 98.55 pg/MUl, serum 39.06 pg/ml), Group 2A (GCF 22.27 pg/MUl, serum 27.73 pg/ml) and lowest (GCF 17.94 pg/MUl, serum 11.49 pg/ml) in Group 1A. Posttreatment groups (1B-4B) showed reduction in the mean IL-18 concentration in both GCF and serum. CONCLUSIONS: As the inflammation increased, there was a concomitant increase in the level of IL 18 and vice versa following periodontal therapy. PMID- 27563199 TI - Evaluation of the relation between anemia and periodontitis by estimation of blood parameters: A cross-sectional study. AB - BACKGROUND: Anemia of chronic disease is defined as anemia occurring in chronic infections, inflammatory conditions, or neoplastic disorders which are not due to marrow deficiencies or other diseases, and occurring despite the presence of adequate iron stores and vitamins. AIMS: To evaluate the relation between anemia and periodontitis by estimation of blood parameters and to assess whether periodontitis like other inflammatory conditions can lead to anemia. It is a randomized controlled clinical trial. MATERIALS AND METHODS: A total of 50 healthy controls, 50 chronic generalized gingivitis, and 50 chronic generalized periodontitis patients were selected. Hemoglobin levels (Hb), erythrocyte count red blood cell, erythrocyte sedimentation rate (ESR), mean corpuscular volu e (MCV), mean corpuscular Hb (MCH) and MCH concentration (MCHC), gingival index, plaque index, probing pocket depth, and clinical attachment level were recorded. Intergroup comparison of blood parameters is by one-way ANOVA. Intergroup pair wise comparison of the three groups is by Newman-Keuls multiple post-hoc procedures. Karl Pearsons's correlation coefficient method is used for correlation between different parameters for three groups. RESULTS: The results revealed a decrease in Hb and erythrocyte counts and increase in white blood corpuscles counts in chronic generalized periodontitis when compared to healthy controls and chronic generalized gingivitis group. There was no statistically significant difference in MCV, MCH, MCHC, and ESR among the groups. CONCLUSIONS: The treatment of periodontitis can lead to an improvement in hematocrit and other related blood parameters in chronic generalized periodontitis patients with anemia. This provides evidence that periodontitis like other chronic diseases may also cause anemia. PMID- 27563200 TI - Microbial contamination of contact lenses after scaling and root planing using ultrasonic scalers with and without protective eyewear: A clinical and microbiological study. AB - BACKGROUND: Ultrasonic scaler is a preferential treatment modality among the clinicians. However, the aerosol/splatter generated is a concern for patients and practitioners. Therefore, the purpose of this study was to evaluate contamination of contact lenses of the dentist after scaling and root planing using ultrasonic scalers with and without protective eyewear. MATERIALS AND METHODS: Thirty patients were randomly selected for scaling and root planing and divided into 2 groups of 15 each. Group A - dentist wearing contact lenses and protective eyewear. Group B - dentist wearing only contact lenses. After scaling and root planing using ultrasonic scalers, the lenses were subjected to culture and 16S rRNA (16S ribosomal RNA) gene sequencing. RESULTS: In Group A - 15 out of thirty samples were contaminated, in Group B - all the thirty samples were contaminated. Most of the samples showed Gram-positive bacteria and 5 samples were contaminated with fungi. 16S rRNA gene sequencing of forty contaminated samples showed that 31 were contaminated with Streptococcus mutans and 9 with Staphylococcus aureus. CONCLUSION: Keeping in mind the limitation of the study for the absence of negative control, we would like to conclude that dental practitioners should better avoid contact lenses in a dental setup because of the risk of contamination of the contact lenses from the various dental procedures which can produce aerosol/splatter and if worn, it is recommended to wear protective eyewear. PMID- 27563201 TI - Prevalence of herpesviruses in gingivitis and chronic periodontitis: relationship to clinical parameters and effect of treatment. AB - BACKGROUND: Assess the prevalence of herpesviruses in healthy subjects, gingivitis, and chronic periodontitis patients, to assess the relationship between the prevalence of herpesviruses and periodontal clinical parameters, and to evaluate the effect of phase-I therapy on the level of viral detection. MATERIALS AND METHODS: Hundred patients consisting of 20 healthy subjects, 40 gingivitis, and 40 chronic periodontitis were included in the study. Clinical parameters recorded included plaque index, gingival index, sulcus bleeding index, probing depth, and clinical attachment level. The gingivitis and chronic periodontitis patients received phase-I periodontal therapy including oral hygiene instructions, full mouth scaling for gingivitis patients and scaling and root planing for chronic periodontitis patients. Gingival crevicular fluid (GCF) was collected, and the presence of herpes simplex virus-1 (HSV-1), HSV-2, cytomegalovirus, and Epstein-Barr virus (EBV) was analyzed using polymerase chain reaction (PCR). Recording of periodontal parameters as well as GCF collection was performed at baseline and 6 weeks postphase-I therapy. RESULTS: At baseline, the levels of HSV-1 and EBV detection were lower in healthy controls as compared to gingivitis (P < 0.05) and chronic periodontitis cases (P < 0.001). Phase-I therapy led to reduction in the amount of HSV-1 and EBV in gingivitis patients (P < 0.05) and for HSV-1, human cytomegalovirus and EBV in chronic periodontitis patients (P < 0.05) in comparison to baseline. The prevalence of EBV in chronic periodontitis patients was positively associated with increased gingival index, probing depth and loss of clinical attachment (P < 0.05). CONCLUSIONS: Higher prevalence of HSV-1 and EBV viruses in GCF of gingivitis and chronic periodontitis suggests a strong association between these viruses and periodontal diseases and periodontal therapy can lead to a reduction in herpesviruses at infected sites. PMID- 27563202 TI - Detection and comparison of Selenomonas sputigena in subgingival biofilms in chronic and aggressive periodontitis patients. AB - BACKGROUND: With the advent of DNA-based culture-independent techniques, a constantly growing number of Selenomonas phylotypes have been detected in patients with destructive periodontal diseases. However, the prevalence levels that have been determined in different studies vary considerably. AIM: The present study was undertaken to detect and compare the presence of Selenomonas sputigena in the subgingival plaque samples from generalized aggressive periodontitis (GAP), chronic generalized periodontitis, and periodontally healthy patients using conventional polymerase chain reaction (PCR) technique. MATERIALS AND METHODS: A total of 90 patients were categorized as periodontally healthy individuals (Group I, n = 30), chronic generalized periodontitis (Group II, n = 30), and GAP (Group III, n = 30). The clinical parameters were recorded and subgingival plaque samples were collected. These were then subjected to conventional PCR analysis. STATISTICAL ANALYSIS USED: Kruskal-Wallis ANOVA test was used for multiple group comparisons followed by Mann-Whitney U-test for pairwise comparison. RESULTS: On comparison between three groups, all the clinical parameters were found to be statistically highly significant. Comparing Groups I-II and I-III, the difference in detection was found to be statistically highly significant whereas in Groups II-III, it was statistically nonsignificant. On comparison of S. sputigena detected and undetected patients to clinical parameters in various study groups, the difference was found to be nonsignificant. CONCLUSION: S. sputigena was found to be significantly associated with chronic and aggressive periodontitis. Although the difference in its detection frequency in both groups was statistically nonsignificant when compared clinically, S. sputigena was more closely associated with the GAP. PMID- 27563203 TI - Histochemical detection and comparison of apoptotic cells in the gingival epithelium using hematoxylin and eosin and methyl green-pyronin: A pilot study. AB - BACKGROUND: Apoptosis plays a critical role in the regulation of inflammation and host immune response. It helps in tissue homeostasis and a disturbance in this is often associated with disease. The use of histochemical stains like hematoxylin and eosin (H and E) and methyl green-pyronin (MGP) can provide a simple and cost effective method for the detection of apoptotic cells. AIM: Study intended to analyze the expression of apoptosis in the gingival epithelium of healthy subjects and in patients with chronic periodontitis, using H and E and MGP. It is also proposed to correlate the apoptotic index (AI) of healthy individuals and those with chronic periodontitis. MATERIALS AND METHODS: Twenty gingival biopsies were harvested from which ten samples were of healthy subjects and ten subjects who suffered from chronic periodontitis. Apoptotic cells were analyzed using MGP and H and E under light microscopy. RESULTS: Apoptotic cells were identified at *100 magnification and AI was calculated. Apoptotic cells were easily distinguishable in MGP stained sections when compared to those stained using H and E. Moreover, apoptotic cell count was higher in chronic periodontitis. Statistical analyses were done by Tukey's multiple post hoc procedure. CONCLUSION: The study reveals that MGP staining can be used in a routine basic laboratory set up as one of the cost-effective methods for the detection of apoptotic cells. PMID- 27563204 TI - Comparative evaluation of probing depth and clinical attachment level using a manual probe and Florida probe. AB - BACKGROUND: To compare and evaluate the intra- and inter-examiner efficacy and reproducibility of the first-generation manual (Williams) probe and the third generation Florida probe in terms of measuring pocket probing depth (PD) and clinical attachment level (CAL). MATERIALS AND METHODS: Forty subjects/4000 sites were included in this comparative, cross-sectional study. Group- and site-wise categorizations were done. Based on gingival index, PD, and CAL, patients were divided into four groups, i.e., periodontally healthy, gingivitis, mild to moderate periodontitis, and severe periodontitis. Further, based on these parameters, a total of 4000 sites, with 1000 sites in each category randomly selected from these 40 patients, were taken. Full mouth PD and CAL measurements were recorded with two probes, by Examiner 1 and on Ramfjord teeth by Examiner 2. RESULTS: Full mouth and Ramfjord teeth group- and site-wise PD obtained with the manual probe by both the examiners were statistically significantly deeper than that obtained with the Florida probe. The full mouth and Ramfjord teeth mean CAL measurement by Florida probe was higher as compared to manual probe in mild to moderate periodontitis group and sites, whereas in severe periodontitis group and sites, manual probe recorded higher CAL as compared to Florida probe. CONCLUSION: Mean PD and CAL measurements were deeper with the manual probe as compared to the Florida probe in all the groups and sites, except for the mild-moderate periodontitis group and sites where the CAL measurements with the manual probe were less than the Florida probe. Manual probe was more reproducible and showed less interexaminer variability as compared to the Florida probe. PMID- 27563205 TI - A comparative evaluation to assess the efficacy of 5% sodium fluoride varnish and diode laser and their combined application in the treatment of dentin hypersensitivity. AB - BACKGROUND: Dentin hypersensitivity (DH) is an age old complaint with a great number of treatment modalities, but none of these are totally effective till date. Lasers being one of the latest treatment options in periodontics, a study was conducted to test the efficacy of diode laser (DL) in DH alone and in comparison with 5% sodium fluoride (NaF) varnish. AIM: The aim of the present study was to compare the effectiveness of 5% topical NaF varnish and 980 nm gallium aluminum arsenide (GaAlAs) DL alone and combination of 5% NaF + 980 nm GaAlAs DL in the management of DH. MATERIALS AND METHODS: The study was conducted on 120 teeth in thirty patients with DH assessed by tactile and air blast (AB) stimuli measured by visual analog scale (VAS). Teeth were randomly divided into Group 1 (P) placebo-treated control group, Group 2 (NaF) treated by 5% NaF varnish, Group 3 (DL) treated with 980 nm DL, and Group 4 (NaF + DL) treated with both 5% NaF varnish and 980 nm DL (combination group). RESULTS: There was a significant reduction in DH. The VAS reduction percentages were calculated, and there was a significant decrease in DH above all in G4 (NaF + DL) than G3 (DL) and G2 (NaF). CONCLUSION: Even though all the three groups (2, 3, and 4) showed improvement in terms of DH reduction, 5% NaF varnish with DL showed the best results among all the groups. PMID- 27563206 TI - Morphological study of proximal root grooves and their influence on periodontal attachment loss. AB - BACKGROUND: The etiology of periodontal diseases is multifactorial including both systemic and local causes. Local factors such as grooves on root surfaces contribute a great deal to the causation of periodontal diseases. MATERIALS AND METHODS: Proximal radicular grooves were studied in 150 extracted maxillary and mandibular anterior teeth. Periodontal attachment loss was measured after staining the root surfaces with 0.1% toluidine blue stain. The relationship of the presence and absence of grooves with periodontal attachment loss was also studied. RESULTS: The prevalence of proximal root grooves was found to be 86.67%. The prevalence of grooves on maxillary teeth was 43.42% and on mandibular teeth was 56.67%. A greater loss of attachment was present on grooved surfaces than on nongrooved surfaces. CONCLUSION: The proximal radicular grooves present as one of the major etiological factors in periodontal diseases. PMID- 27563207 TI - Variations in the frenal morphology in the diverse population: A clinical study. AB - BACKGROUND: The upper labial frenum is a normal anatomic structure with inherent morphological variations. Frenum has variations depending upon the attachment of fibers along with the presence of structural variations. AIM: The aim of this study was to evaluate the prevalence of frenal variations in a diverse ethnic population of Sundernagar, Himachal Pradesh. MATERIALS AND METHODS: This study was conducted on 500 subjects within age group of 16-40 years (285 females, 215 males). Intraoral examination was done to evaluate the variations in frenum and photographs were taken. RESULTS: In this study, depending upon structural variations, normal frenum was most common followed by frenum with nodule while frenum with appendix was found to be least common. However, no significant difference was found between males and females (P > 0.05) with respect to all frenal attachments. Furthermore, other structural variations were found in the diverse population of Sundernagar, Himachal Pradesh. CONCLUSION: Upper labial frenum is a small anatomical landmark in the oral cavity found to have diverse morphology. The dentist needs to give due importance for frenum assessment during the oral examination. PMID- 27563208 TI - Association of chronic periodontitis with metabolic syndrome: A cross-sectional study. AB - BACKGROUND: Prevalence of metabolic syndrome (MeS) is high among Asians, including Indians and is rising, particularly with the adoption of modernized lifestyle. Various studies have reported a significant relationship between periodontal status and MeS. The objective of this study is to investigate the association between periodontitis and MeS. MATERIALS AND METHODS: The study included 259 subjects (130 cases with chronic periodontitis, 129 controls without chronic periodontitis) who underwent medical and periodontal checkup. Five components (obesity, high blood pressure, low- and high-density lipoproteins, cholesterol, hypertriglyceridemia, and high plasma glucose) of MeS were evaluated, and individuals with >=3 positive components were defined as having MeS. The periodontal parameter was clinical attachment level (CAL) on the basis of which cases were selected with moderate (CAL loss 3-4 mm) and severe (CAL loss >=5 mm) generalized chronic periodontitis. The association between chronic periodontitis and MeS components was investigated using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The association of MeS and chronic periodontitis was strong and significant with OR: 2.64, 95% CI: 1.36-5.18, and P < 0.003. Comparison of mean values of components of MeS between cases and controls reveals that the mean waist circumference (mean difference: -4.8 [95% CI: 7.75--1.84], P < 0.002) and mean triglycerides level (mean difference: -25.75 [95% CI: -49.22--2.28], P < 0.032) were significantly higher in cases than in control groups. Although mean systolic blood pressure, diastolic blood pressure, and fasting blood sugar level were higher in cases (125.77, 82.99 and 86.38, respectively) compared with control (122.81, 81.3 and 83.68, respectively), it was statistically insignificant. CONCLUSION: The results of this study suggest that there is a strong association between chronic periodontitis and MeS. The association was independent of the various potential confounding risk factors affecting the chronic periodontitis such as age, sex, residential background, and tobacco consumption. PMID- 27563209 TI - The impact of lifestyles on the periodontal health of adults in Udupi district: A cross sectional study. AB - OBJECTIVES: (1) To assess the impact of different lifestyle factors on periodontal health of adults. (2) To assess the impact of overall/combined lifestyle variable (calculated by health practice index [HPI]) on periodontal health of adults. MATERIALS AND METHODS: A cross-sectional study consisting of a structured questionnaire on HPI, oral health-related behavior, and personal habits as well as sociodemographic variables was conducted on 800 subjects aged 20-50 years attending dental outreach set-ups of Manipal College of Dental Sciences, Manipal. Clinical examination for periodontal status was done by recording loss of attachment scores using community periodontal index (FDI/WHO 1982). Statistical analysis was done by bivariate analysis using Chi-square followed by multivariate analysis to obtain adjusted odds ratio with 95% confidence interval. RESULTS: After adjusting for all the confounding variables in multivariate logistic regression analysis, the variables that showed an independent association with periodontitis were age, location, marital status, smoking, hours of sleep per night, physical activity, and overall poor lifestyles. CONCLUSION: Our results support studying a combined approach using various lifestyle behaviors for controlling chronic periodontitis. Necessary public health action on conditions which determine unhealthy lifestyle behaviors across population is needed which is possible by patient's involvement in self care by promoting healthy lifestyles. PMID- 27563210 TI - Management of a rare case of peripheral squamous odontogenic tumor of the gingiva. AB - Odontogenic tumors (OTs) arising from the periodontium are quite rare. Squamous OT (SOT) is one such neoplasm which has an exceedingly rare occurrence. According to the literature, there have been very few reported cases of SOT with a very small percentage involving the gingiva. Most of the times, these tumors are located within the bone, only a very few peripheral cases been noted so far. Although predominantly benign, the possibility of a malignant transformation prevails. Our case describes a rare presentation of a peripheral SOT involving the upper anterior gingiva in a 59-year-old patient, which presented clinically as a firm and fibrotic swelling. An excisional biopsy was performed as a part of surgical management and for microscopic evaluation to confirm the clinical diagnosis. A soft tissue graft was harvested from an edentulous area to cover the deficit at the surgical site. The patient was evaluated at periodic intervals to assess the healing outcome and for any recurrence of the lesion. PMID- 27563211 TI - Desquamative gingivitis as only presenting sign of mucous membrane pemphigoid. AB - Desquamative gingivitis (DG) is a clinical condition in which the gingiva appears reddish, glazed, and friable with loss of superficial epithelium. DG is considered a clinical manifestation of many gingival diseases and hence not identified as a diagnosis itself. Mucous membrane pemphigoid (MMP) is an autoimmune vesiculobullous disorder of mucous membrane characterized by subepithelial bullae formation. MMP can affect the mucous membranes of oral cavity, conjunctiva, nasopharynx, larynx, esophagus, genitourinary tract, and anus and vary in its severity. The most commonly affected sites are oral cavity and conjunctiva. Since DG may be the early sign or only presenting sign of these conditions, most of the times, dental surgeon plays a key role in the diagnosis and prevention of the systemic complications of these diseases. We report a case of a 41-year-old male patient presented with DG. Histopathological examination revealed subepithelial clefting suggestive of MMP. The patient was treated with topical application of triamcinolone acetonide 0.1% 3-4 times a day for 1 month. PMID- 27563212 TI - "United Pedicle Flap" for management of multiple gingival recessions. AB - Numerous surgical procedures have evolved and are being modified with time to treat gingival recession by manipulating gingival or mucosal tissues in various ways. However, the decision to choose the most appropriate technique for a given recession site still remains a challenging task for clinicians. Mucogingival deformities such as shallow vestibule, frenal pull, or inadequate attached gingiva complicate the decision and limit the treatment options to an invasive procedure involving soft tissue grafts. The situation is further comprised if there is a nonavailability of adequate donor tissue and patients' unwillingness for procedures involving a second surgical site. In such situations, the recession either remains untreated or has poor treatment outcomes. This case report presents a modified pedicle graft technique for treatment of multiple gingival recessions with shallow vestibule and inadequate attached gingiva. The technique is a promising therapeutic alternative to invasive surgical procedures such as soft tissue grafts for treatment of multiple gingival recessions. PMID- 27563213 TI - Periodontium bestows vision!! AB - The role of periodontium in supporting the tooth structures is well-known. However, less is known about its contribution to the field of ophthalmology. Corneal diseases are among major causes of blindness affecting millions of people worldwide, for which synthetic keratoprosthesis was considered the last resort to restore vision. Yet, these synthetic keratoprosthesis suffered from serious limitations, especially the foreign body reactions invoked by them resulting in extrusion of the whole prosthesis from the eye. To overcome these shortcomings, an autologous osteo-odonto keratoprosthesis utilizing intraoral entities was introduced that could positively restore vision even in cases of severely damaged eyes. The successful functioning of this prosthesis, however, predominantly depended on the presence of a healthy periodontium for grafting. Therefore, the following short communication aims to acknowledge this lesser-known role of the periodontium and other oral structures in bestowing vision to the blind patients. PMID- 27563214 TI - A New Sucrase Enzyme Inhibitor from Azadirachta indica. AB - BACKGROUND: Sucrase enzyme inhibitor considered as an oral anti-diabetic therapy that delays the absorption of eaten carbohydrates, reducing the postprandial glucose and insulin peaks to reach normoglycemia. MATERIALS AND METHODS: Chromatographic fractionation of the hydroalcoholic extract of leaves of Azadirachta indica growing in KSA, followed by in-vitro assay of sucrase enzyme inhibition activity. RESULTS: This investigation led to the isolation of a new remarkable sucrase enzyme inhibitor; 4'-methyl Quercetin-7-O-beta-D glucuronopyranoside (1) alongside with four known compounds; 2,3 hexahydroxydiphenoyl-(alpha/beta)-D-(4)C1-glucopyranose (2), Avicularin (3), Castalagin (4) and Quercetin-3-O-glucoside (5). The structure of the new compound (1) was elucidated on the basis of its spectral data, including ESI-MS, UV, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, HSQC, NOESY and HMBC. CONCLUSION: Under the assay conditions, hydroalcoholic extract of A. indica and compounds 1-5 exhibited significant sucrase enzyme inhibitory activity. SUMMARY: Chromatographic fractionation of the hydroalcoholic extract of leaves of Azadirachta indica, led to the Isolation of a new flavonoid glycoside named 4'-methyl Quercetin-7-O-beta D-glucuronopyranoside, alongside to other 4 known polyphenols. The hydroalcoholic extract as well as the isolated compounds exhibited significant sucrase enzyme inhibitory activity. Abbreviations used: ESI-MS; electrospray ionization-mass spectrometry, UV; ultraviolet, NMR; nuclear magnetic resonance, 1H-1H COSY; 1H-1H correlation spectroscopy, NOESY; nuclear overhauser effect spectroscopy, and HSQC; heteronuclear multiple bond correlation. A. indica; Azadirachta indica. PMID- 27563215 TI - Screening of Chonemorpha fragrans Bioactive Extracts for Cytotoxicity Potential and Inhibition Studies of Key Enzymes Involved in Replication. AB - BACKGROUND: Chonemorpha fragrans (Moon) Alston, a liana belonging to family Apocynaceae, is used in traditional medicinal systems for the treatment of various ailments. It is an unexplored medicinal plant with respect to its anticancer potential. OBJECTIVE: Cytotoxicity of sequential as well as crude extracts of in vivo plant parts (leaves, bark, and roots), in vitro cultures, and callus were compared. MATERIALS AND METHODS: 3-(4,5- dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell proliferation assay was used to compare the extracts of various in vivo plant parts (leaves, bark, and roots) along with in vitro culture systems (in vitro plantlets, callus). Furthermore, the extracts were used to evaluate inhibition of key enzymes involved in replication, i.e. topoisomerase (Topo) I and II, DNA polymerase, to check the probable mechanism of action for this cytotoxicity. RESULTS: MTT assay showed that the chloroform extract of callus has potent anticancer potential. The plant has a promising anticancer activity against human colon epithelium, lung carcinoma, and epidermoidal carcinoma cell lines. It was found to possess Topo as well as DNA polymerase inhibitory activity. CONCLUSION: The results have pointed toward pharmaceutical importance of this plant. This study is the first report of exploring the antiproliferative potential as well as inhibition studies of key enzymes involved in replication, which was useful to point out probable mechanism of action for extracts of C. fragrans. SUMMARY: It's a first report of cytotoxicity studies and inhibition of enzyme involved in the replication process by Chonemorpha fragrans plant extracts. The results reveal the pharmaceutical importance of this plant. From various assays performed here, a potent anticancer potential of chloroform extract of callus was revealed showing Topo I (E. coli and human) inhibitory activity, DNA pol inhibitory activity. Considering the importance of these activities, plant further needs to be explored in detail for in vivo cancer studies as well as for its metabolite content. Abbreviations used: CPT: Camptothecin, EDTA: Ethylenediaminetetraacetic acid, MTT: 3-4,5 dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, Pol: Polymerase, Topo - Topoisomerase. PMID- 27563216 TI - Storing of Extracts in Polypropylene Microcentrifuge Tubes Yields Contaminant Peak During Ultra-flow Liquid Chromatographic Analysis. AB - BACKGROUND AND AIM: This study was designed to understand the effect of storage in polypropylene microcentrifuge tubes and glass vials during ultra-flow liquid chromatographic (UFLC) analysis. MATERIALS AND METHODS: One ml of methanol was placed in polypropylene microcentrifuge tubes (PP material, Autoclavable) and glass vials (Borosilicate) separately for 1, 2, 4, 8, 10, 20, 40, and 80 days intervals stored at -4 degrees C. RESULTS: Contaminant peak was detected in methanol stored in polypropylene microcentrifuge tubes using UFLC analysis. The contaminant peak detected was prominent, sharp detectable at 9.176 +/- 0.138 min on a Waters 250-4.6 mm, 4 MU, Nova-Pak C18 column with mobile phase consisting of methanol:water (70:30). CONCLUSION: It was evident from the study that long-term storage of biological samples prepared using methanol in polypropylene microcentrifuge tubes produce contaminant peak. Further, this may mislead in future reporting an unnatural compound by researchers. SUMMARY: Long-term storage of biological samples prepared using methanol in polypropylene microcentrifuge tubes produce contaminant peakContamination peak with higher area under the curve (609993) was obtained in ultra-flow liquid chromatographic run for methanol stored in PP microcentrifuge tubesContamination peak was detected at retention time 9.113 min with a lambda max of 220.38 nm and 300 mAU intensity on the given chromatographic conditionsGlass vials serve better option over PP microcentrifuge tubes for storing biological samples. Abbreviations used: UFLC: Ultra Flow Liquid Chromatography; LC: Liquid Chromatography; MS: Mass spectrometry; AUC: Area Under Curve. PMID- 27563217 TI - Isolation and Structure Determination of 24-Methylenecycloartanyl Ferulate from Indian Rice Bran and Its Quantitative Analysis. AB - BACKGROUND: gamma-oryzanol is a major bioactive constituent in rice. Most of the literature reports isolation of 24-methylenecycloartanyl ferulate (24-mCAF) from rice bran oil (RBO) of other than Indian variety. Current research has successfully applied high-performance thin layer chromatography (HPTLC) method for isolation of 24-mCAF from Indian variety (Indrayani) of RBO. MATERIALS AND METHODS: HPTLC method was developed for standard gamma-oryzanol using tinidazole as an internal standard. The proposed HPTLC method was optimized and validated as per the guidelines stated by the International Conference on Harmonization Q2 R1 recommendations. The mobile phase composed of toluene:ethyl acetate:methanol (15.0:1.7:3.3, (v/v/v) was selected because well-resolved peaks were obtained. The optimum wavelength chosen for detection and quantitation was 317 nm. RESULTS: The retention factors for tinidazole, 24-mCAF, and CAF were found to be 0.27 +/- 0.02, 0.72 +/- 0.02, and 0.79 +/- 0.02, respectively. The percent content of 24 mCAF in ethanol fraction was found to be 1.02%. The 24-mCAF was isolated from RBO using HPTLC method. CONCLUSION: The characterization data of 1D, 2D spectral analysis confirm that the isolated compound 1 is 24-mCAF. SUMMARY: HPTLC method was developed for standard gamma-oryzanol using tinidazole as an internal standardThe proposed HPTLC method was optimized and validated as per the guidelines stated by the ICH Q2 R1 recommendationsThe characterization data of 1D, 2D spectral analysis confirms that the isolated compound is 24 methylenecycloartanyl ferulateIn this work, high purity 24-mCAF was successfully isolated from crude RBO using HPTLC with a solvent system composed toluene: ethyl acetate: methanol (15.0:1.7:3.3, v/v/v) Abbreviations used: RBO: Rice Bran Oil, CAF: Cycloartenol ferulic acid, 24-mCAF: 24-Methylcycloartenol ferulic acid, HPLC: High-Performance Liquid Chromatography, HPTLC: High-Performance Thin Layer Chromatography, 1H: Proton nuclear magnetic resonance spectroscopy, 13C: Carbon 13 nuclear magnetic resonance spectroscopy, COSY: Correlation spectroscopy, NOESY: Nuclear overhauser effect spectroscopy, HMBC: Heteronuclear multiple bond correlation nuclear magnetic resonance spectroscopy, HSQC: heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy. PMID- 27563218 TI - Elicitation Based Enhancement of Secondary Metabolites in Rauwolfia serpentina and Solanum khasianum Hairy Root Cultures. AB - BACKGROUND: Rauwolfia serpentina and Solanum khasianum are well-known medicinally important plants contained important alkaloids in their different parts. Elicitation of these alkaloids is important because of associated pharmaceutical properties. Targeted metabolites were ajmaline and ajmalicine in R. serpentina; solasodine and alpha-solanine in S. khasianum. OBJECTIVE: Enhancement of secondary metabolites through biotic and abiotic elicitors in hairy root cultures of R. serpentina and S. khasianum. MATERIALS AND METHODS: In this report, hairy root cultures of these two plants were established through Agrobacterium rhizogenes mediated transformation by optimizing various parameters as age of explants, duration of preculture, and co-cultivation period. NaCl was used as abiotic elicitors in these two plants. Cellulase from Aspergillus niger was used as biotic elicitor in S. khasianum and mannan from Saccharomyces cerevisiae was used in R. serpentina. RESULTS: First time we have reported the effect of biotic and abiotic elicitors on the production of important metabolites in hairy root cultures of these two plants. Ajmalicine production was stimulated up to 14.8 fold at 100 mM concentration of NaCl after 1 week of treatment. Ajmaline concentration was also increased 2.9-fold at 100 mg/l dose of mannan after 1 week. Solasodine content was enhanced up to 4.0-fold and 3.6-fold at 100 mM and 200 mM NaCl, respectively, after 6 days of treatments. CONCLUSION: This study explored the potential of the elicitation strategy in A. rhizogenes transformed cell cultures and this potential further used for commercial production of these pharmaceutically important secondary metabolites. SUMMARY: Hairy roots of Rauwolfia serpentina were subjected to salt (abiotic stress) and mannan (biotic stress) treatment for 1 week. Ajmaline and ajmalicine secondary metabolites were quantified before and after stress treatmentAjmalicine yield was enhanced up to 14.8-fold at 100 mM concentration of NaCl. Ajmaline content was also stimulated 2.9-fold at 100 mg/l dose of mannan after 1 weekHairy roots of Solanum khasianum were treated with cellulase (biotic elicitor) and salt (abiotic stress)Solasodine content was improved up to 4.0-fold and 3.6-fold at 100 mM and 200 mM NaCl, respectively, after 6.days of treatmentsThe alpha-solanine content increased to 1.6-fold after 24 h of treatment at 100 MUg/mL cellulase concentration. Abbreviations used: MS medium: Murashige and Skoog medium, B5 medium: Gamborg B5 medium, OD: Optical Density, NaCl: Sodium Chloride. PMID- 27563219 TI - Catha edulis Extract Induces H9c2 Cell Apoptosis by Increasing Reactive Oxygen Species Generation and Activation of Mitochondrial Proteins. AB - BACKGROUND: Catha edulis (Khat) is an evergreen shrub or small tree, traditionally used by various peoples of the Arabian Peninsula and Africa as an integral component of the socioeconomic traditions. It is believed that the psychostimulant nature and toxic nature of khat is primarily due to the presence of cathinone and cathine respectively. Studies have shown that khat chewing is closely associated with cardiac complications, especially myocardial infarction. Hence in this study, we exposed cathine-rich khat extract in a cardiomyoblast H9c2 (2-1) cell line to check the cell death mechanism. MATERIALS AND METHODS: Extraction of Catha edulis leaves was done and the presence of cathine was confirmed with LC-MS-MS. The anti-proliferative activity was assayed using MTT and apoptosis detection by acridine orange/propidium iodide assay. The expression of Bcl-2 and Bax protein and caspase-3/7 expression were analyzed. The level of reactive oxygen species generation was also evaluated. RESULTS: The khat extract showed an IC50 value of 86.5 MUg/ml at 48 hours treatment. We have observed significant early apoptosis events by intervened acridine orange within the fragmented DNA with bright green fluorescence upon treatment. The Bcl-2 expression in the treatment with IC50 concentration of khat extract for 24, 48 and 72 hours of incubation significantly decreased with increase in bax level. The increased activation of caspase-3/7 was significantly observed upon treatment together with significant increase of ROS was detected at 24 and 48 hours treatment. CONCLUSION: Collectively, our results provide insight into the mechanisms by which Catha edulis leaves mediate cell death in cardiomyocytes. SUMMARY: Catha edulis (Khat) is an evergreen psychotropic shrub or small treeExtraction of khat leaves was done and the presence of cathine was confirmed with liquid chromatography-mass spectrometry-mass spectrometryThe khat extract showed an IC(50) value of 86.5 MUg/ml at 48 h treatment in H9c2 (2-1) cell lineThe observed cell death was associated with increased expression of Bcl2 and caspase-3Significant increase of reactive oxygen species was also detected in the cell with treatment. Abbreviations used: CNS: central nervous system; AMI: acute myocardial infarction; TLC: thin layer chromatography; ESI: electrospray ionization; FBS: fetal bovine serum; DMSO: dimethylsulfoxide; AO; acridine orange; PI; propidium iodide; HRP: horseradish peroxidase; HBSS: hank's balanced salt solution; DCFH-DA: 2',7'-dichlorofluorescin diacetate; NAC, 10 mM: NAC: N acetyl cysteine; ROS: reactive oxygen species. PMID- 27563220 TI - Purified Essential Oil from Ocimum sanctum Linn. Triggers the Apoptotic Mechanism in Human Breast Cancer Cells. AB - BACKGROUND: Essential oil of Ocimum sanctum Linn. exhibited various pharmacological activities including antifungal and antimicrobial activities. In this study, we analyzed the anticancer and apoptosis mechanisms of Ocimum sanctum essential oil (OSEO). OBJECTIVE: To trigger the apoptosis mechanism in human breast cancer cells using OSEO. MATERIALS AND METHODS: OSEO was extracted using hydrodistillation of the leaves. Cell proliferation was determined using different concentrations of OSEO. Apoptosis studies were carried out in human breast cancer cells using propidium iodide (PI) and Hoechst staining. RESULTS: We found that OSEO inhibited proliferation (IC50 = 170 MUg/ml) of Michigan cancer foundation-7 (MCF-7) cells in a dose-dependent manner. The OSEO also induced apoptosis as evidenced by the increasing number of PI-stained apoptotic nucleic of MCF-7 cells. Flow cytometry analysis revealed that treatment with OSEO (50-500 MUg/ml) increased the apoptotic cells population (16-84%) dose dependently compared to the control. OSEO has the ability to up-regulate the apoptotic genes p53 and Bid and as well as elevates the ratio of Bax/Bcl-2. CONCLUSION: Our findings indicate that OSEO has the ability as proapoptotic inducer and it could be developed as an anticancer agent. SUMMARY: OSEO inhibited proliferation of MCF 7 cells with an IC50 of 170 MUg/mLOSEO at 500 MUg/mL increased the population of apoptotic cells by 84%OSEO up-regulated the expression of apoptotic genes and as well increased the Bax/Bcl2 ratio. Abbreviations used: BAX: BAX BCL2-associated X protein; BCL2: B-cell CLL/lymphoma 2; BID: BH3 Interacting domain death agonist; OSEO: Ocimum sanctum essential oil; DMSO: Dimethyl sulfoxide; DMEM: Dulbecco's modified Eagle medium; MCF-7: Michigan cancer foundation-7; RT-PCR: Real Time Polymerase Chain Reaction. PMID- 27563221 TI - A New Octadecenoic Acid Derivative from Caesalpinia gilliesii Flowers with Potent Hepatoprotective Activity. AB - BACKGROUND: Caesalpinia gilliesii Hook is an ornamental shrub with showy yellow flowers. It was used in folk medicine due to its contents of different classes of secondary metabolites. In our previous study, dichloromethane extract of C. gilliesii flowers showed a good antioxidant activity. AIM OF THE STUDY: Isolation and identification of bioactive hepatoprotective compounds from C. gilliesii flowers dichloromethane fraction. MATERIALS AND METHODS: The hepatoprotective activity of dichloromethane fraction and isolated compounds were studied in CCl4 intoxicated rat liver slices by measuring liver injury markers (alanine aminotransferase, aspartate aminotransferase and glutathione [GSH]). All compounds were structurally elucidated on the basis of electron ionization-mass spectrometry, one- and two-dimensional nuclear magnetic resonance. RESULTS: A new 12,13,16-trihydroxy-14(Z)-octadecenoic acid was identified in addition to the known beta-sitosterol-3-O-butyl, daucosterol, isorhamnetin, isorhamnetin-3-O rhamnoside, luteolin-7,4'-dimethyl ether, genistein-5-methyl ether, luteolin-7-O rhamnoside, isovanillic acid, and p-methoxybenzoic acid. Dichloromethane fraction and isorhamnetin were able to significantly protect the liver against intoxication. Moreover, the dichloromethane fraction and the isolated phytosterols induced GSH above the normal level. CONCLUSION: The hepatoprotective activity of C. gilliesii may be attributed to its high content of phytosterols and phenolic compounds. SUMMARY: Bioactive Hepatoprotective phytosterols and phenolics from chloroform extract of Caesalpinia gilliesii Abbreviations used: ALT: Alanine Aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione; SC50: Scavenging Capacity 50 (SC 50); COSY: Correlation spectroscopy; NMR: Nuclear Magnetic Resonance; CC: Column chromatography; EI-MS: Electron-impact mass spectrometry; HSQC: Heteronuclear single-quantum correlation. PMID- 27563223 TI - New Abietane Diterpenes from Euphorbia Pseudocactus Berger (Euphorbiaceae) and Their Antimicrobial Activity. AB - BACKGROUND: Euphorbia is the largest genus in Euphorbiaceae. Terpenoids were isolated from most species of this genus. OBJECTIVE: Since no previous study was reported about Euphorbia pseudocactus Berger, we started here a phytochemical investigation on this species to isolate and identify its terpenoid constituents and to estimate the antimicrobial activity of the isolated compounds. MATERIALS AND METHODS: The n-hexane fraction of the ethanolic extract of E. pseudocactus Berger was chromatographed on silica gel columns, the structures of the isolated compounds (1-5) were identified based on their MS, 1 D, and 2 D NMR spectral data. The antimicrobial activity of the n-hexane fraction and the isolated compounds (1-4) was investigated using diffusion plate method against Gram positive (Staphylococcus aureus [12600] and Bacillus subtilis [6051]) and Gram negative (Pseudomonas aeruginosa [10145] and Escherichia coli [11775]) bacteria, yeast (Candida albicans [7102]), and fungi (Aspergillus flavus). RESULTS: Two triterpenes (glut-5-en-3 beta-ol [1] and olean-12,15-diene-3 beta-ol [2]) and three abietane diterpene (3-hydoxy-19-cyclopropenoyloxy-abietane [3], ent-abieta 9,12,14-triene-12,16-olide [4], and 12,19-dihydroxy-abieta-5-ene [5]) were isolated. Compound 1 exhibited no antibacterial activity against the tested bacteria, compound 2 and n-hexane fraction exhibited weak activity, whereas compounds 3 and 4 showed moderate activity. All samples showed no activity against the tested yeast and fungi. DISCUSSION AND CONCLUSION: Five compounds were isolated for the 1(st) time from E. pseudocactus Berger, three of them (3-5) are new natural compounds. As the major isolated compound (1) exhibited no antimicrobial activity, the observed activity of the n-hexane fraction is mainly due to its diterpenoid constituents. SUMMARY: Two known triterpenes and three new diterpenes were isolated from n-hexane fraction of Euphorbia pseudocactusThe abietane diterpenoids showed higher antimicrobial activity than n-hexane fraction. Abbreviations used: EtOAc: Ethyl acetate, TLC: Thin layer chromatography. PMID- 27563222 TI - Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity. AB - OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl4)-induced injury. MATERIALS AND METHODS: Hepatotoxicity was induced by a single dose of CCl4 (1 ml/kg, IP). One day after, rats were received SIL (200 mg/kg) alone or in combination with CA (60 mg/kg) and/or ME (20 mg/kg) for 21 days. RESULTS: SIL significantly decreased serum alanine aminotransferase, inflammatory cytokines, and vascular endothelial growth factor levels. Histological alterations, fibrogenesis, oxidative DNA damage, inflammatory mediators, and caspase-3 activity were significantly attenuated in SIL treated CCl4-intoxicated rats. On the other hand, cytochrome P450 2E1 activity showed a significant decrease in the liver of CCl4-intoxicated rats, an effect that was reversed following treatment with SIL. All beneficial effects of SIL were markedly potentiated when combined with CA and/or ME. CONCLUSIONS: These data indicate that SIL, alone and combined with CA and/or ME, protected the liver against CCl4-induced hepatotoxicity via attenuating inflammation, oxidative DNA damage, apoptosis, and fibrotic changes. The significantly intensified hepatoprotective effects of SIL when combined with both CA and ME suggest a possible synergism. These synergistic effects need to be further confirmed using detailed studies. SUMMARY: Silymarin, chlorogenic acid and melatonin possess in vivo hepatoprotective activitySilymarin, chlorogenic acid and melatonin attenuate fibrogenesis, oxidative DNA damage, inflammation and apoptosisChlorogenic acid and melatonin enhance the hepatoprotective effect of silymarin. Abbreviations used: SIL: silymarin, CA: chlorogenic acid, ME: melatonin, CCl4: carbon tetrachloride, CYP2E1, cytochrome P450 2E1, ALT: alanine aminotransferase, IL-6: interleukin 6, IFN-gamma: interferon gamma, VEGF: vascular endothelial growth factor, TNF-alpha: tumor necrosis factor alpha, CRP: C-reactive protein, 8-OxodG: 8-Oxo-2'-deoxyguanosine, TGF-B1: transforming growth factor beta 1, HSCs: hepatic stellate cells. PMID- 27563224 TI - Cocculus hirsutus: Molecular Docking to Identify Suitable Targets for Hepatocellular Carcinoma by In silico Technique. AB - BACKGROUND: Protein-ligand interaction plays a major role in identification of the possible mechanism by which a ligand can bind with the target and exerts the pharmacological action. OBJECTIVE: The aim is to identify the best candidate of Cocculus hirsutus which binds with the hepatocellular carcinoma (HCC) targets by docking studies. MATERIALS AND METHODS: The reported phytoconstituents such as coclaurine, hirsutine, cohirsine, cohirsinine, lirioresinol, cohirsitinine, haiderine, jamtinine, isotrilobine, shaheenine, jamtine, and cocsoline present in the plant, C. hirsutus were docked with the HCC targets such as Aurora kinase, c Kit, fibroblast growth factor, nuclear factor kappa B (NF-kB), B-cell lymphoma extra large, and vascular endothelial growth factor (VEGF) using in silico technique with the software Grid-Based Ligand Docking with Energies. RESULTS: Haiderine, shaheenine, and coclaurine had good interaction with Aurora kinase with the glide score and glide energy of - 7.632, -7.620, -7.464; and - 56.536, 55.203, -52,822, respectively. Coclaurine, lirioresinol, and haiderine possess good binding with c-Kit with the glide score and glide energy of - 8.572, -6.640, -6.478; and - 56.527, -57.138, -20,522, respectively. Lirioresinol, hirsutine, and coclaurine exhibit good binding with c-Kit with the glide score and glide energy of - 5.702, -5.694, -5.678; and - 48.666, -35.778, -41,673, respectively. Similarly, coclaurine, haiderine, and hisutine had good interaction with NF-kB. Haiderine, jamtinine, and coclaurine had good binding with VEGF receptors (VEGFR) and coclaurine, lirioresinol, and haiderine exhibit good bonding with VEGFR. CONCLUSION: Coclaurine, haiderine, and lirioresinol exibited good hydrogen bonding interactions and binding energy with the select targets. Hence, these compounds have to be taken up for experimental work against hepatocellular carcinoma. SUMMARY: Compounds of interest showed good interaction and binding with the selected targets. Hence these compounds has to be explored further to study their anticancer potentials. Abbreviations used: HCC: Hepatocellular Carcinoma, Bcl-xL: B-cell lymphoma-extra large, FGF: Fibroblast Growth Factor, VEGF: Vascular Endothelial Growth Factor, DLA: Dalton's Lymphoma Ascites. PMID- 27563225 TI - Assessment of the Polyphenolic Content, Free Radical Scavenging, Anti inflammatory, and Antimicrobial Activities of Acetone and Aqueous Extracts of Lippia javanica (Burm.F.) Spreng. AB - BACKGROUND: Lippia javanica (Burm.F.) Spreng is one of the spice plants commonly found in almost every part of South Africa. Apart from its culinary uses, it is also traditionally used as an insect repellant and infusion for fever, flu, kidney stone treatment, cough, common cold, and chest pain. MATERIALS AND METHODS: The antioxidant activities of the aqueous and acetone extracts were determined by measuring their effects against 1,1-Diphenyl-2-picryl-hydrazyl, 2,2'azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), nitric oxide, phosphomolybdate, lipid peroxidation, hydrogen peroxide, and reducing power. The antimicrobial activities were evaluated against four bacterial (two Gram positive, two Gram-negative) strains and 9 fungal pathogens using the agar well diffusion and microdilution methods. Anti-inflammatory activity was assessed by determining the inhibition against protein denaturation and membrane stabilizing effects. OBJECTIVE: The polyphenolic content, free radical scavenging, anti inflammatory, and antimicrobial activities of the aqueous and acetone extracts of the plant were evaluated. RESULTS: A significantly high total phenolic content and free radical scavenging activities were observed in the acetone extracts of the plants. The study also revealed a concentration-dependent inhibition of protein denaturation and membrane stabilization effects by both the aqueous and acetone extracts at the concentrations studied. The ability of L. javanica extracts to inhibit protein denaturation and maintain membrane stability could be responsible for its folkloric use. The overall antimicrobial activity indicates that both extracts were active against the bacterial strains but the acetone extract exhibited the most potent antifungal activity higher than even the reference drugs. CONCLUSION: Overall, the acetone extract of L. javanica exhibited a more pronounced antioxidant, anti-inflammatory, and antimicrobial effects than the aqueous extract. SUMMARY: The polyphenolic content and biological activities of the spice plant, Lippia javanica from South Africa was evaluatedSignificantly high polyphenolic content and free radical scavenging activities were observed for both extractsModerate antimicrobial action, concentration-dependent inhibition of protein denaturation and membrane haemolysis were also observed. Abbreviations used: AA: ascorbic acid, ABTS: 2,2'azino-bis (3-ethylbenthiazoline-6-sulfonic acid), BHT: Butylated hydroxytoluene, DPPH: 1,1-Diphenyl-2-picryl-hydrazyl, NBT: 2,2'-di-pnitrophenyl 5,5'-diphenyl-(3,3'-dimethoxy-4,4'-diphenylene)- ditetrazolium chloride, PMS: Potassium metabisulfite, ROS: Reactive oxygen species, TBA: Thiobarbituric acid, TCA: Trichloroacetic acid. PMID- 27563226 TI - Potency of Massoia Bark in Combating Immunosuppressed-related Infection. AB - BACKGROUND: As part of our search for new potential natural resources to eradicate infection, we have revealed the prominent potency of massoia bark (Massoia aromatica Becc, Lauraceae) in combating immunosuppressed-related infection. MATERIALS AND METHODS: The extract was prepared by macerating the pulverized dried bark in ethanol 95%, followed by solvent evaporation. The oil was extracted from the dried bark by steam-hydrodistillation of which preparative thin-layer chromatography was performed on the oil to isolate the active constituent, C-10 massoia lactone (ML). Anti-biofilm assay against Candida albicans was conducted on polystyrene 96 wells microtiter plates, followed by a confocal laser scanning microscope observation to get three-dimensional profiles of the affected biofilms. Effects on the hyphae development inoculated on RPMI 1640 agar plates were observed for 7 days. Influences of samples on mice macrophage phagocytosis were examined by an in vitro technique. Samples concentration tested were in the range of 2.0-0.0625 mg/mL and done in triplicate. RESULTS: Massoia bark extracts (oil and solid phase) and ML exhibited promising activities as anti-biofilm against C. albicans at IC50 0.074% v/v, 271 MUg/mL and 0.026 MUg/mL, respectively. The ML did not inhibit the hyphae development at the concentration tested; however, the extracts showed inhibition at 62.5 MUg/mL. Macrophage phagocytosis stimulation was correlated to the ML content. CONCLUSION: Massoia bark is potential to be developed as anti-infective in immunosuppressed condition of which the C10 ML (C10H16O2) plays a major role in exerting activity. SUMMARY: Massoia bark extracts (oily and solid phase) and C 10 Massoia lactone exhibited promising activities as antibiofilm against Candida albicans at IC50 are 0.074 %v/v, 271 MUg/mL and 0.026 MUg/mL respectively. The major constituent, C-10 Massoia lactone (C10H16O2) plays major role in exerting anticandida activity and potentially acts as an immunomodulator as well. However extracts showed inhibition of hyphae development of C. albicans which showed no correlation to the content of the Massoia lactone. Abbreviations used: GC/MS: Gas Chromatography/Mass Spectrometry, ML: Massoia Lactone, TLC: Thin Layer Chromatography, ATCC: American Type Culture Collection, RPMI: Roswell Park Memorial Institute, PBS: Phosphate Buffer Sterile, LSM: Laser scanning microscope, DMSO: Dimethyl sulfoxide, UV: Ultra violet, SDB: Sabouraud dextrose agar, MeOH: Methanol, LB: Luria Bertani, EtOAc: Ethyl acetate, CLSM: Confocal Laser Scanning Microscope, PI: Propidium iodide. PMID- 27563227 TI - The Antioxidant Potential of Azadirachta indica Ameliorates Cardioprotection Following Diabetic Mellitus-Induced Microangiopathy. AB - BACKGROUND: Cardiac complications associated with diabetes mellitus have become major cause of concern. Antidiabetic drugs, with varied mode of action, are although available, apprehensions exist for their limited action or side effects upon prolonged use. Efforts are therefore inclined toward finding other alternatives. The present study was, thus, undertaken to evaluate the cardioprotective effect of Azadirachta indica (AI) on microangiopathic changes in rat model of diabetes. MATERIALS AND METHODS: Diabetes was induced in male rats by single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Seven days after glucose levels are stabilized, aqueous leaf extract of AI (ALE) (600 mg/kg(1) body weight) was administered orally to diabetic animals every day for 7 days. RESULTS: High blood glucose characterizing diabetes in these animals was found to show increased lipid peroxidation (LPO), altered antioxidant biomarkers together with microangiopathic alterations. The treatment of diabetic rats with ALE reduced the levels of blood glucose, LPO, and restored the activities of antioxidant enzyme. Light and transmission electron microscopic analysis revealed reduced necrotic areas and inflammation in tissue architecture of ALE treated heart in comparison to untreated diabetic group. CONCLUSION: AI provides cardioprotection by ameliorating oxidative stress in rat model of diabetic mellitus. SUMMARY: The streptozotocin (STZ) treatment (60 mg/kg body weight) to animals induced diabetic changes such as elevated blood glucose levels, decreased body weight, altered lipid profiles together with development of proxidant state evidenced by elevated levels of lipid peroxidation (LPO), depletion in reduced glutathione (GSH) levels and altered antioxidant enzymes with consequent microangiopathic alterations in heart tissue evinced by localization of necrotic and inflamed areas in heart tissueThe treatment of animals with Azadirachta indica leaf extract (ALE) (600 mg/kg body weight) post STZ treatment significantly reversed the adverse effects witnessed by normalized blood glucose levels, improvement in reduced body weight and stabilized lipid profilesFurther, ALE treatment also significantly reduced the LPO indices, improvement in GSH content and restoration of antioxidant enzyme activities, suggesting antioxidatant potential of ALEThe microangiopathic changes in the heart tissue consequent to induction of diabetes and oxidative stress by STZ as reiterated through light microscopy and transmission electron microscopy were found to be reversed by ALE treatment. These observations pointed toward cardiopreventive effects of ALE following microangiopathic changes as seen following induction of diabetes mellitus. Abbreviations used: AI: Azadirachta indica, ALE: Azadirachta indica Leaves Extract. STZ: Streptozotocin, LPO Lipid per oxidation, GSH: Glutathione, GSSG: Glutathione disulphide, SOD: Superoxide dismutase, GP: Glutathione peroxidase, GR: Glutathione reductase. PMID- 27563228 TI - DNA-based Simultaneous Identification of Three Terminalia Species Targeting Adulteration. AB - BACKGROUND: Various parts of three Terminalia species, namely, Terminalia arjuna (stem bark), Terminalia bellirica (fruit), and Terminalia chebula (fruit) are widely known for their therapeutic principles and other commercial values. However, stem bark of T. bellirica and T. chebula along with Terminalia tomentosa are reported as adulterants of T. arjuna. Correct botanical identification is very critical for safe and effective herbal drugs. DNA-based identification approaches are advancing the conventional methods and sometime proved more beneficial. OBJECTIVE: The purpose of the study was to develop polymerase chain reaction (PCR) method using internal transcribed spacer (ITS) region to ascertain the identity of T. arjuna herbal material as well as detection of mixing of other three Terminalia species. MATERIALS AND METHODS: DNA from stem barks samples were isolated and subjected to ITS region amplification and sequencing. Sequences were compared for polymorphic nucleotides determination to develop species-specific primers. Final primers were selected on the basis of in silico analysis and experimentally validated. PCR assays for botanical identification of Terminalia species were developed. Sensitivity testing and assay validation were also performed. RESULTS: The PCR assays developed for Terminalia species were resulted in definite amplicons of the corresponding species. No cross-reactivity of the primers was detected. Sensitivity was found enough to amplify as low as 2 ng of DNA. Mixing of DNA in various concentrations for validation also proved the sensitivity of assay to detect original botanicals in the mixture. The developed methods proved very specific and sensitive to authenticate Arjuna bark to develop evidence-based herbal medicines. SUMMARY: Internal transcribed spacer-based species-specific polymerase chain reaction.(PCR) assays were developed to authenticate Terminalia arjuna stem bark and to identify substitution/adulteration of Terminalia bellirica and Terminalia chebula in the genuine starting materialDefinite amplicons were obtained specific to particular species and the assay was found of profound sensitivity to amplify as low as 2 ng of DNAResults of method validation proved that the assay can identify adulterant Terminalia species even when present in lower amountsThe DNA barcodes and PCR methods can also be used to identify Terminalia bellirica and T. chebula related herbal medicinal material. Abbreviations used: ITS: Internal transcribed spacer, BSA: Bovine serum albumin, DMSO: Dimethyl sulfoxide. PMID- 27563229 TI - Efficiency of matK, rbcL, trnH-psbA, and trnL-F (cpDNA) to Molecularly Authenticate Philippine Ethnomedicinal Apocynaceae Through DNA Barcoding. AB - BACKGROUND: The Philippines is home to some ethnomedicinal Apocynaceae that has been used to cure common ailments. They are perceived to be safe, but misidentification can lead to substitution and adulteration. Morphological characters are primarily utilized to identify these species but a new method utilizing molecular characters called DNA barcoding has emerged. In this study, the efficiency of matK, rbcL, trnH-psbA, and trnL-F to molecularly authenticate selected Apocynaceae species were tested. MATERIALS AND METHODS: Genomic DNA from silica-dried leaf samples were isolated and used as a template for generating DNA barcodes. Pair-wise sequence divergence using Kimura-2-Parameter was used to analyze inter-specific and intraspecific variations among the barcodes, whereas basic local alignment search tool (BLAST) and neighbor-joining (NJ) analyses were employed to examine discrimination success. RESULTS: The results show that matK is the best barcode for Apocynaceae as it has the highest amplification and sequencing success together with rbcL while having high inter-specific and low intra-specific divergence relative to the other candidate barcodes. Furthermore, matK provided the highest discrimination both in BLAST and NJ analyses. CONCLUSION: This study proposes the use of matK as the principal barcode for Apocynaceae. SUMMARY: Both matK and rbcL have higher universality compared to trnH-psbA and trnL-F matK has relatively high inter-specific divergence and very minimal intra-specific divergencematK is the best barcode to molecularly authenticate Apocynaceae with either trnH-psbA or trnL-F as supplements. Abbreviations used: K2P: Kimura-2-parameter, BLAST: Basic local alignment search tool, NJ: Neighbor-joining. PMID- 27563230 TI - Beyond Sub-Gaussian Measurements: High-Dimensional Structured Estimation with Sub Exponential Designs. AB - We consider the problem of high-dimensional structured estimation with norm regularized estimators, such as Lasso, when the design matrix and noise are drawn from sub-exponential distributions. Existing results only consider sub-Gaussian designs and noise, and both the sample complexity and non-asymptotic estimation error have been shown to depend on the Gaussian width of suitable sets. In contrast, for the sub-exponential setting, we show that the sample complexity and the estimation error will depend on the exponential width of the corresponding sets, and the analysis holds for any norm. Further, using generic chaining, we show that the exponential width for any set will be at most [Formula: see text] times the Gaussian width of the set, yielding Gaussian width based results even for the sub-exponential case. Further, for certain popular estimators, viz Lasso and Group Lasso, using a VC-dimension based analysis, we show that the sample complexity will in fact be the same order as Gaussian designs. Our general analysis and results are the first in the sub-exponential setting, and are readily applicable to special sub-exponential families such as log-concave and extreme-value distributions. PMID- 27563231 TI - Contact-mediated control of radial migration of corneal epithelial cells. AB - PURPOSE: Patients with a heterozygous mutation in the gene encoding the transcription factor, PAX6, have a degenerative corneal opacity associated with failure of normal radial epithelial cell migration across the corneal surface and a reported wound healing defect. This study investigated the guidance mechanisms that drive the directed migration of corneal epithelial cells. METHODS: In vivo corneal epithelial wounding was performed in adult wild-type and Pax6(+/-) mice, and the healing migration rates were compared. To investigate the control of the cell migration direction, primary corneal epithelial cells from wild-type and Pax6(+/-) mice were plated on grooved quartz substrates, and alignment relative to the grooves was assayed. A reconstructed corneal culture system was developed in which dissociated wild-type and genetically mutant corneal epithelial cells could be cultured on a de-epithelialized corneal stroma or basement membrane and their migration assayed with time-lapse microscopy. RESULTS: The Pax6(+/-) cells efficiently re-epithelialized corneal wounds in vivo but had mild slowing of healing migration compared to the wild-type. Cells aligned parallel to quartz grooves in vitro, but the Pax6(+/-) cells were less robustly oriented than the wild-type. In the reconstructed corneal culture system, corneal epithelial cells continued to migrate radially, showing that the cells are guided by contact mediated cues from the basement membrane. Recombining wild-type and Pax6 mutant corneal epithelial cells with wild-type and Pax6 mutant corneal stroma showed that normal Pax6 dosage was required autonomously in the epithelial cells for directed migration. Integrin-mediated attachment to the substrate, and intracellular PI3Kgamma activity, were required for migration. Pharmacological inhibition of cAMP signaling randomized migration tracks in reconstructed corneas. CONCLUSIONS: Striking patterns of centripetal migration of corneal epithelial cells observed in vivo are driven by contact-mediated cues operating through an intracellular cAMP pathway, and failure to read these cues underlies the migration defects that accompany corneal degeneration in patients with mutations in PAX6. PMID- 27563232 TI - Increased levels of IL-6, sIL-6R, and sgp130 in the aqueous humor and serum of patients with diabetic retinopathy. AB - PURPOSE: Trans-signaling of interleukin (IL)-6 through its soluble receptor (sIL 6R) is critically involved in the promotion of chronic inflammatory diseases. The aim of the present study was to estimate IL-6, sIL-6R, and soluble gp130 (sgp130, a natural antagonist of IL-6 trans-signaling) concentrations in the serum and aqueous humor (AqH) of patients with diabetic retinopathy (DR). METHODS: Paired AqH and serum samples were collected from 152 consecutive diabetic patients (105 with DR and 47 without DR, NDR) and 51 healthy controls. The IL-6, sIL-6R, and sgp130 concentrations were measured with multiplex bead immunoassay. RESULTS: The sgp130 concentrations in the serum and AqH were statistically significantly elevated in patients with DR compared with the NDR patients and the healthy controls (p<0.001). The sgp130 concentrations in the serum and AqH increased as the DR severity increased (p = 0.008, p<0.001, respectively). Higher serum and AqH concentrations of IL-6 and sIL-6R were also observed in patients with DR when compared with the NDR patients and the healthy controls (p<0.001). The AqH concentration of sgp130 was found to be statistically significantly correlated with sIL-6R and IL-6. Similarly, the IL-6 concentration in the AqH was statistically significantly correlated with sIL-6R (p<0.001). Elevated sgp130, sIL-6R, and IL-6 concentrations in the AqH were associated with longer disease duration and higher body mass index, plasma glucose, and glycosylated hemoglobin (HbA1c). CONCLUSIONS: The sgp130, IL-6, and sIL-6R concentrations were statistically significantly elevated in patients with DR, suggesting a probable contributing role of the IL-6 trans-signaling pathway to the pathophysiology of DR. PMID- 27563233 TI - Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes. AB - AIM: Our specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists' diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes. METHODS: We evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation. We focused on extraocular thrombotic events, particularly pregnancy complications, including unexplained spontaneous abortion, pre-eclampsia eclampsia. Thrombophilia measurements in the 76 females were compared with 62 healthy normal females without ocular vascular occlusions (OVOs). RESULTS: The 76 females with OVO were more likely than 62 normal female controls to have high homocysteine (24% vs 0%, P<0.0001), high anticardiolipin antibody (immunoglobulin M, 17% vs 3%, P=0.012), high (>150%) factor VIII (42% vs 11%, P<0.0001), and high (>150%) factor XI (22% vs 4%, P=0.004). Of the 76 females, 26 (34%) had >=1 spontaneous abortion; 17 (22%) had >=2 spontaneous abortions and/or pre-eclampsia eclampsia. Compared to 62 healthy female controls, these 17 females with pregnancy complications had high homocysteine (29% vs 0%, P=0.0003), high anticardiolipin antibody immunoglobulin M (24% vs 3%, P=0.02), high factor VIII (38% vs 11%, P=0.02), and were marginally more likely to be heterozygous for the factor V Leiden mutation (19% vs 3%, P=0.058). CONCLUSION: In females lacking typical risk factors for retinal vascular occlusion or severely ischemic presentation, by diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy, with particular relevance to pregnancy outcomes and venous thromboembolism. PMID- 27563234 TI - Effects of salvianolate on bone metabolism in glucocorticoid-treated lupus-prone B6.MRL-Fas (lpr) /J mice. AB - AIM: To investigate the bone-protective effects of salvianolate (Sal), a total polyphenol from Radix Salviae miltiorrhizae, on bone tissue in the spontaneous lupus-prone mouse model, B6.MRL-Fas (lpr) /J, undergoing glucocorticoid (GC) treatment. METHODS: Fifteen-week-old female B6.MRL-Fas (lpr) /J mice were administered either a daily dose of saline (lupus group), prednisone 6 mg/kg (GC group), Sal 60 mg/kg (Sal group); or GC plus Sal (GC + Sal group) for a duration of 12 weeks. Age-matched female C57BL/6J wild-type (WT) mice were used for control. Micro-computed tomography assessments, bone histomorphometry analysis, bone biomechanical test, immunohistochemistry and immunoblotting analysis for bone markers, and renal histology analysis were performed to support our research endeavor. RESULTS: Lupus mice developed a marked bone loss and deterioration of mechanical properties of bone due to an increase in bone resorption rather than suppression of bone formation. GC treatment strongly inhibited bone formation in lupus mice. Sal treatment significantly attenuated osteogenic inhibition, and also suppressed hyperactive bone resorption, which recovered the bone mass and mechanical properties of bone in both the untreated and GC-treated lupus mice. CONCLUSION: The data support further preclinical investigation of Sal as a potential therapeutic strategy for the treatment of systemic lupus erythematosus related bone loss. PMID- 27563235 TI - Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy. AB - Fibroblast growth factor receptors (FGFRs) are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V), was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE), and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody-drug conjugates. The FGF1V-valine-citrulline-MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE) upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V-vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. PMID- 27563236 TI - PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome. AB - The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Mullerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting <=15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (<=75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women <35 years and was 33.2% for the group aged 35-39 years. Routine use of both algorithms led to only 11.6% of women generating >15 oocytes, significantly lower than recently published data applying conventional dosages (38.2%; P<0.0001). When comparing both specific algorithms to each other, the outcomes were mainly comparable for pregnancy, live birth, and miscarriage rate. However, there were significant differences in relation to number of oocytes retrieved, but the mean for both the algorithms remained well below 15 oocytes. Consequently, application of both these algorithms in our in vitro fertilization clinic allows the use of both the rFSH products, with very similar results, and they can be considered validated on the basis of effectiveness and safety, clearly avoiding ovarian hyperstimulation syndrome. PMID- 27563237 TI - Schizophrenia relapse, patient considerations, and potential role of lurasidone. AB - When treating persons with schizophrenia, delaying time to relapse is a main goal. Antipsychotic medication has been the primary treatment approach, and there are a variety of different choices available. Lurasidone is a second-generation (atypical) antipsychotic agent that is approved for the treatment of schizophrenia and bipolar depression. Three long-term studies of lurasidone have examined time to relapse in persons with schizophrenia, including a classic placebo-controlled randomized withdrawal study and two 12-month active comparator studies (vs risperidone and vs quetiapine extended-release). Lurasidone 40-80 mg/d evidenced superiority over placebo (number needed to treat [NNT] vs placebo for relapse, 9). Lurasidone 40-160 mg/d was noninferior to quetiapine extended release 200-800 mg/d on the outcome of relapse, and was superior on the outcome of avoidance of hospitalization (NNT 8) and the outcome of remission (NNT 7). Lurasidone demonstrated a lower risk for long-term weight gain than the active comparators. Demonstrated differences in tolerability profiles among the different choices of antipsychotics make it possible to attempt to match up an individual patient to the best choice for such patient based on past history of tolerability, comorbidities, and personal preferences, potentially improving adherence. PMID- 27563238 TI - Evaluating the fall risk among elderly population by choice step reaction test. AB - Falls during daily activities are often associated with injuries and physical disabilities, thereby affecting quality of life among elder adults. Balance control, which is crucial in avoiding falls, is composed of two elements: muscle strength and central nervous system (CNS) control. A number of studies have reported that reduced muscle strength raises the risk of falling. However, to date there has been only limited research focused on the relationship between fall risk and the CNS. This study aimed to investigate the relationship between CNS and risk of falling among the elderly. A total of 140 elderly people (92 females and 48 males) were divided into faller and nonfaller groups based on questionnaire responses concerning falls in their daily life. Participants undertook a choice step reaction test in which they were required to respond to random visual stimuli using foot movements as fast as possible in the left or right directions. Response time was quantified as premotor time (PMT) and motor time (MT). In addition, the participants' electro-myography data were recorded during the choice step reaction test. A maximal isokinetic torque test was also performed. PMT was greater in the fallers than in the nonfallers group. There was a significant difference between fall status and direction on PMT. PMT of the left limb in nonfallers was faster than the right, but in fallers there was no difference between left and right limbs. A similar phenomenon was also observed for MT. There were significant differences between fallers and nonfallers in maximum isokinetic torque at knee and ankle joints. The correct rate of PMT was higher than other variables, such as MT and maximal isokinetic torque, in evaluating elderly fall risk by using logistic regression analyses. The results suggest that PMT in the choice step reaction test could be a useful parameter to assess risk of fall among elder adults. In addition, decreased maximal isokinetic torque was related to greater PMT and disappearance of asymmetry in older adults who were at higher risk of fall, especially in the lower limb. PMID- 27563239 TI - Community-acquired pneumonia and survival of critically ill acute exacerbation of COPD patients in respiratory intensive care units. AB - PURPOSE: The aim of this study was to appraise the effect of community-acquired pneumonia (CAP) on inhospital mortality in critically ill acute exacerbation of COPD (AECOPD) patients admitted to a respiratory intensive care unit. PATIENTS AND METHODS: A retrospective observational study was performed. Consecutive critically ill AECOPD patients receiving treatment in a respiratory intensive care unit were reviewed from September 1, 2012, to August 31, 2015. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed by Mann-Whitney U-test. Kaplan-Meier analysis was used to assess the association of CAP with survival of critically ill AECOPD patients for univariate analysis. Cox's proportional hazards regression model was performed to identify risk factors for multivariate analysis. RESULTS: A total of 80 consecutive eligible individuals were reviewed. These included 38 patients with CAP and 42 patients without CAP. Patients with CAP had a higher inhospital rate of mortality than patients without CAP (42% vs 33.3%, P<0.05). Kaplan-Meier survival analysis showed that patients with CAP had a worse survival rate than patients without CAP (P<0.05). Clinical characteristics, including Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein, and CAP, were found to be closely associated with survival of AECOPD individuals. Further multivariate Cox regression analysis confirmed that CAP and APACHE II were independent risk factors for inhospital mortality in critically ill AECOPD patients (CAP: hazard ratio, 5.29; 95% CI, 1.50-18.47, P<0.01 and APACHE II: hazard ratio, 1.20; 95% CI, 1.06-1.37, P<0.01). CONCLUSION: CAP may be an independent risk factor for higher inhospital mortality in critically ill AECOPD patients. PMID- 27563240 TI - Inhibition of E. coli and S. aureus with selenium nanoparticles synthesized by pulsed laser ablation in deionized water. AB - Nosocomial diseases are mainly caused by two common pathogens, Escherichia coli and Staphylococcus aureus, which are becoming more and more resistant to conventional antibiotics. Therefore, it is becoming increasingly necessary to find other alternative treatments than commonly utilized drugs. A promising strategy is to use nanomaterials such as selenium nanoparticles. However, the ability to produce nanoparticles free of any contamination is very challenging, especially for nano-medical applications. This paper reports the successful synthesis of pure selenium nanoparticles by laser ablation in water and determines the minimal concentration required for ~50% inhibition of either E. coli or S. aureus after 24 hours to be at least ~50 ppm. Total inhibition of E. coli and S. aureus is expected to occur at 107+/-12 and 79+/-4 ppm, respectively. In this manner, this study reports for the first time an easy synthesis process for creating pure selenium to inhibit bacterial growth. PMID- 27563241 TI - Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis. AB - BACKGROUND: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges. PURPOSE: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases. MATERIALS AND METHODS: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, zeta-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals. RESULTS: Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart. CONCLUSION: These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity. PMID- 27563242 TI - Decreased Pseudomonas aeruginosa biofilm formation on nanomodified endotracheal tubes: a dynamic lung model. AB - Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation that has been shown to be associated with increased mortality rates and medical costs in the pediatric intensive care unit. Currently, there is no cost-effective solution to the problems posed by VAP. Endotracheal tubes (ETTs) that are resistant to bacterial colonization and that inhibit biofilm formation could provide a novel solution to the problems posed by VAP. The objective of this in vitro study was to evaluate differences in the growth of Pseudomonas aeruginosa on unmodified polyvinyl chloride (PVC) ETTs and on ETTs etched with a fungal lipase, Rhizopus arrhizus, to create nanoscale surface features. These differences were evaluated using an in vitro model of the pediatric airway to simulate a ventilated patient in the pediatric intensive care unit. Each experiment was run for 24 hours and was supported by computational models of the ETT. Dynamic conditions within the ETT had an impact on the location of bacterial growth within the tube. These conditions also quantitatively affected bacterial growth especially within the areas of tube curvature. Most importantly, experiments in the in vitro model revealed a 2.7 log reduction in the number (colony forming units/mL) of P. aeruginosa on the nanoroughened ETTs compared to the untreated PVC ETTs after 24 hours. This reduction in total colony forming units/mL along the x-axis of the tube was similar to previous studies completed for Staphylococcus aureus. Thus, this dynamic study showed that lipase etching can create surface features of nanoscale roughness on PVC ETTs that decrease bacterial attachment of P. aeruginosa without the use of antibiotics and may provide clinicians with an effective and inexpensive tool to combat VAP. PMID- 27563244 TI - Association of depression with sleep quality might be greater than that of pain intensity among outpatients with chronic low back pain. AB - PURPOSE: No study to date has compared the associations of pain intensity, depression, and anxiety with insomnia among outpatients with chronic low back pain (CLBP). This study aimed to investigate this issue. PATIENTS AND METHODS: A total of 225 outpatients with CLBP were enrolled from a general orthopedics clinic. The Insomnia Severity Index was used to evaluate sleep quality. Major depressive disorder (MDD) and anxiety disorders were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, Axis I Disorders. Two psychometric scales were used to evaluate depression and anxiety. The Visual Analog Scale was employed to assess pain intensity. Multiple linear regressions were performed to determine the association of insomnia with pain intensity, depression, and anxiety. RESULTS: Among the 225 subjects, 58 (25.8%) had clinical insomnia; 83 (36.9%) had severe low back pain; 49 (21.8%) had MDD, including 21 (9.3%) with a current major depressive episode (MDE); and 52 (23.1%) had anxiety disorders. More than half (56.9%) of the subjects with CLBP and clinical insomnia had MDD and/or anxiety disorders. Subjects with a current MDE or anxiety disorders had greater severities of pain and insomnia as compared with subjects without these conditions. After controlling for demographic variables, MDE was more strongly associated with insomnia than severe low back pain; moreover, the severity of depression had a greater association with insomnia than pain intensity. CONCLUSION: The association of depression with insomnia was not inferior to that of pain intensity with insomnia. Among patients with CLBP and insomnia, integration of depression and anxiety treatment into treatment of pain might help to improve sleep quality. PMID- 27563243 TI - The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5. AB - Diseases caused by bacterial and fungal pathogens are among the major health problems in the world. Newer antimicrobial therapies based on novel molecules urgently need to be developed, and this includes the antimicrobial peptides. In spite of the potential of antimicrobial peptides, very few of them were able to be successfully developed into therapeutics. The major problems they present are molecule stability, toxicity in host cells, and production costs. A novel strategy to overcome these obstacles is conjugation to nanomaterial preparations. The antimicrobial activity of different types of nanoparticles has been previously demonstrated. Specifically, magnetic nanoparticles have been widely studied in biomedicine due to their physicochemical properties. The citric acid modified manganese ferrite nanoparticles used in this study were characterized by high-resolution transmission electron microscopy, which confirmed the formation of nanocrystals of approximately 5 nm diameter. These nanoparticles were able to inhibit Candida albicans growth in vitro. The minimal inhibitory concentration was 250 ug/mL. However, the nanoparticles were not capable of inhibiting Gram negative bacteria (Escherichia coli) or Gram-positive bacteria (Staphylococcus aureus). Finally, an antifungal peptide (Cm-p5) from the sea animal Cenchritis muricatus (Gastropoda: Littorinidae) was conjugated to the modified manganese ferrite nanoparticles. The antifungal activity of the conjugated nanoparticles was higher than their bulk counterparts, showing a minimal inhibitory concentration of 100 ug/mL. This conjugate proved to be nontoxic to a macrophage cell line at concentrations that showed antimicrobial activity. PMID- 27563245 TI - Prognostic indicators for failed nonsurgical reduction of intussusception. AB - PURPOSE: To identify the risk factors for failure of nonsurgical reduction of intussusception. METHODS: Data from intussusception patients who were treated with nonsurgical reduction in Chiang Mai University Hospital and Siriraj Hospital between January 2006 and December 2012 were collected. Patients aged 0-15 years and without contraindications (peritonitis, abdominal X-ray signs of perforation, and/or hemodynamic instability) were included for nonsurgical reduction. The success and failure groups were divided according to the results of the reduction. Prognostic indicators for failed reduction were identified by using generalized linear model for exponential risk regression. The risk ratio (RR) was used to report each factor. RESULTS: One hundred and ninety cases of intussusception were enrolled. Twenty cases were excluded due to contraindications. A total of 170 cases of intussusception were included for the final analysis. The significant risk factors for reduction failure clustered by an age of 3 years were weight <12 kg (RR =1.48, P=0.004), symptom duration >3 days (RR =1.26, P<0.001), vomiting (RR =1.63, P<0.001), rectal bleeding (RR =1.50, P<0.001), abdominal distension (RR =1.60, P=0.003), temperature >37.8 degrees C (RR =1.51, P<0.001), palpable abdominal mass (RR =1.26, P<0.001), location of mass (left over right side) (RR =1.48, P<0.001), poor prognostic signs on ultrasound scans (RR =1.35, P<0.001), and method of reduction (hydrostatic over pneumatic) (RR =1.34, P=0.023). The prediction ability of this model was 82.21% as assessed from the area under the receiver operating characteristic curve. CONCLUSION: The identified prognostic factors for the nonsurgical reduction failure may help to predict the reduction outcome and provide information to the parents. PMID- 27563246 TI - Risk impact of edoxaban in the management of stroke and venous thromboembolism. AB - The new generation of target-specific oral anticoagulants is being prescribed for increasing numbers of patients at risk of stroke or venous thromboembolism (VTE). These drugs offer valuable benefits due to fast onset anticoagulation, a fixed anticoagulation effect (allowing administration of specified doses), and no requirement for routine monitoring. Edoxaban is a fast-acting oral anticoagulant, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and in the treatment of acute VTE. Like many of the new oral anticoagulants, it selectively inhibits factor Xa, in a concentration-dependent manner. Multiple Phase II clinical trials have shown edoxaban to be noninferior to vitamin K antagonists in the prevention of stroke and VTE, with a good safety profile. To date, the pivotal studies to endorse edoxaban's clinical use have been ENGAGE AF-TIMI and Hokusai-VTE, both of which have compared its efficacy to standard warfarin treatment. This paper aims at reviewing the use of edoxaban in the management of stroke and thromboembolic disease, highlighting the key study results that have led to its current license. PMID- 27563247 TI - Oncogenic NanogP8 expression regulates cell proliferation and migration through the Akt/mTOR signaling pathway in human gastric cancer - SGC-7901cell line. AB - BACKGROUND: Although elevated expression of NanogP8 has been detected in many human tumor tissues, its role in gastric tumorigenesis remains unclear. Therefore, this study aimed to investigate the function and regulatory mechanism of NanogP8 in gastric cancer. METHODS: In this study, NanogP8 cDNA was amplified by real time polymerase chain reaction from the human gastric cancer cell line SGC-7901. The shRNA for RNA interference was established. The NanogP8, pAkt, Akt, pERK, ERK, p-mTOR, and mTOR proteins were detected by using the Western blot assay. Cell viability was evaluated by using the CCK-8 assay. Cell migration and invasion were also examined by using the transwell assay. RESULTS: The results indicated that the NanogP8 overexpression promoted proliferation and migration of SGC-7901 cell line, whereas its ablation exerted opposite effects. Interestingly, NanogP8 activated Akt, a key mediator of survival signals, and without affecting total Akt protein level. The NanogP8-increased gastric cell proliferation was downregulated by Akt inhibition. Our results further showed that increasing NanogP8 expression in human gastric cancer cells promoted cell proliferation by activating the AKT/mTOR pathway and further maintained gastric cell survival. CONCLUSION: Our findings extend the knowledge regarding the oncogenic functions and proved that the NanogP8 regulates cell proliferation and migration by Akt/mTOR signaling pathway in human gastric cancer SGC-7901cell line. PMID- 27563248 TI - A rare case report of primary bone lymphoma and a brief review of the literature. AB - Primary bone lymphoma is a rare and peculiar extranodal presentation of non Hodgkin's lymphoma, which threatens human health. It can be defined as a lymphoma that occurs in the bone, consisting of a single bone lesion with or without regional lymphadenopathies, and its underlying causes are largely unknown. In this case report, we describe a male who presented with left-sided distal forearm pain, swelling of 2 months duration, and progressive limited wrist motion for about 1 month. The patient had no significant medical history except diabetes. Magnetic Resonance Imaging demonstrated a sheet-like bone destruction area in the left-sided radius, localized discontinuous bone cortex, and adjacent soft tissue masses. Finally, a bone biopsy examined by histopathological and immunochemical methods confirmed a diagnosis of primary bone diffuse large B-cell lymphoma. Due to the rarity of this disease, the level of evidence supporting some diagnostic and therapeutic decisions remains low, and therefore, the details of the rare case may facilitate treatment of similar diseases and provide insight about this obscure lymphoproliferative malignancy. Also, related recent literature reports of primary bone lymphoma are reviewed. PMID- 27563249 TI - Antihormonal treatment associated musculoskeletal pain in women with breast cancer in the adjuvant setting. AB - PURPOSE: Antihormonal treatment is an effective therapy in the adjuvant setting. However, musculoskeletal pain is a common adverse effect encountered in patients receiving this treatment. We aimed to evaluate the risk factors for the development of antihormonal treatment-associated musculoskeletal pain (AHAMP) and its impact on the health-related quality of life (HRQOL). PATIENTS AND METHODS: A cross-sectional survey of 78 consecutive breast cancer patients receiving adjuvant antihormonal treatment for early-stage breast cancer in an academic medical oncology clinic was conducted. AHAMP was assessed by Health Assessment Questionnaire (HAQ) and 10 cm visual analog scale (VAS). HRQOL was assessed by self-administered short form 36 and Functional Assessment of Cancer Therapy Breast subscale surveys. RESULTS: AHAMP was found to be present in 37 (47.7%) patients. In multivariate regression analysis, having a normal body mass index (<30 kg/m(2)), cigarette smoking, and low serum vitamin D level (20 ng/mL) were found to be independent risk factors. In HRQOL assessment, physical and mental scores were found to be significantly lower in patients with joint arthralgia. CONCLUSION: AHAMP has an adverse effect on the quality of life of breast cancer patients receiving adjuvant antihormonal treatment, and assessment of predictive factors is important for identification of patient groups at risk of developing this condition. PMID- 27563250 TI - Anorectal melanoma metastatic to the breast: a case report and review of the literature. AB - Melanoma develops from melanocytes and typically occurs on the skin and mucosa with a high degree of malignancy. Intensive local invasion and distant metastasis of melanoma result in poor patient prognosis, owing to frequent metastases to the lungs, bones, brains, and other parts of the body. In the present study, we report a case of anorectal melanoma in a 56-year-old woman who was admitted to our hospital because of local recurrence 9 months after local resection. She subsequently underwent radical surgery. Metastasis to the left breast occurred within 4 months after radical surgery. Metastasis of anorectal melanoma to the breast is very rare. In the present case report and literature review, we analyzed the clinical manifestation, diagnosis, and treatment of anorectal melanoma metastatic to the breast. PMID- 27563251 TI - ATG7 promotes the tumorigenesis of lung cancer but might be dispensable for prognosis predication: a clinicopathologic study. AB - Lung cancer is the most frequent cause of cancer-related death worldwide. Dysregulated autophagy is often observed in lung cancer. Autophagy-related 7 (ATG7) is an autophagy gene that is essential for the biogenesis of autophagosomes. Although ATG7-deficient mouse models have demonstrated that ATG7 dependent autophagy is required for lung cancer tumorigenesis, the relationship between ATG7 expression levels and human lung cancer is unclear. Here, we demonstrate that ATG7 was overexpressed in human lung cancer tissues compared with normal tissues. However, ATG7 expression was not associated with tumor differentiation, tumor size, or TNM stage. Moreover, the overexpression of ATG7 did not influence the overall survival of the lung cancer patients. Therefore, our results indicate that ATG7 might be dispensable for tumor growth and chemotherapy efficacy in human lung cancer. PMID- 27563252 TI - Clinical implications of transforming growth factor-beta-induced gene-h3 protein expression in lung cancer. AB - AIM: The clinical implications of transforming growth factor-beta-induced gene-h3 (beta-IGH3) protein expression in lung cancer remain unclear. This study investigated beta-IGH3 protein expression levels and biological function, as well as lung cancer prognosis. METHODS: Beta-IGH3 protein expression levels were measured in 236 lung cancers and were matched with adjacent noncancerous tissues by immunohistochemical staining. Subsequently, the relationship between beta-IGH3 protein expression, clinical-pathological parameters, and lung cancer prognosis was evaluated. RESULTS: Beta-IGH3 protein expression was significantly higher in lung cancer tissues compared with adjacent noncancerous tissues (61.86% vs 22.88%; P=0.01). Of the 236 enrolled cases, 146 (61.86%) showed high beta-IGH3 levels. Tumor size, clinical stage, and lymph node metastasis were significantly related to beta-IGH3 protein expression in univariate analysis (P=0.001, 0.044, and 0.029, respectively), whereas age, sex, and histological type were not (P=0.038, 0.756, and 0.889, respectively). Finally, a Cox regression model also identified beta-IGH3 as an independent prognostic factor (P=0.01). CONCLUSION: Beta-IGH3 is highly expressed in lung cancers and may be a potential target for lung cancer treatments. PMID- 27563253 TI - Successful treatment of angiosarcoma of the scalp with apatinib: a case report. AB - Angiosarcoma is a rare and aggressive vascular malignancy with a poor prognosis. There is no standard chemotherapy regime for advanced angiosarcoma. Here, we report a case of advanced angiosarcoma that was successfully treated with apatinib, an oral tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2 (VEGFR-2). To our knowledge, this is the first case to report the successful use of apatinib for angiosarcoma. Furthermore, the administration of apatinib results in fewer toxic effects than traditional cytotoxic chemotherapy. Quantitative polymerase chain reaction analysis revealed high expression of VEGFR-2 mRNA, suggesting that apatinib leads to clinical response by inhibiting VEGFR-2 tyrosine kinase activity and that VEGFR-2 plays a crucial role for angiosarcoma. Apatinib may be an additional option for angiosarcoma especially for the aged and patients with poor performance status. Further prospective studies are required to optimize the use of apatinib in patients with angiosarcoma and to identify which patients will benefit from the agent. PMID- 27563254 TI - Comparison of efficacy and safety of two starting insulin regimens in non-Asian, Asian Indian, and East Asian patients with type 2 diabetes: a post hoc analysis of the PARADIGM study. AB - OBJECTIVE: The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L) in insulin-naive patients with type 2 diabetes from different racial/ethnic groups. METHODS: Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89). RESULTS: All subgroups recorded glycated hemoglobin (HbA1c) reductions: non-Asian (LM25, -2.07%; G+L, -2.05%), Asian Indian (LM25, -1.75%; G+L, -1.60%), and East Asian (LM25, -2.03%; G+L, 1.76%); end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%) reached HbA1c <7% versus non-Asians (LM25, 51.7%; G+L, 48.1%); differences were not significant (P=0.12 and P=0.06, respectively). The mean total daily insulin dose (U/kg) for non-Asians was 0.67 (LM25) and 0.61 (G+L), for Asian Indians was 0.91 (LM25) and 0.90 (G+L), and for East Asians was 0.53 (LM25) and 0.59 (G+L). The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.19+/-0.23, for Asian Indians was 0.33+/-0.25, and for East Asians was 0.34+/-0.27. Overall incidence (%) of hypoglycemia in non Asians was 94.1 (LM25) and 91.8 (G+L), in Asian Indians was 90.4 (LM25) and 88.5 (G+L), and in East Asians was 69.8 (LM25) and 77.3 (G+L). CONCLUSION: Asian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the LM25 arm with a lower rate of hypoglycemia. Asians required more mealtime insulin coverage than non-Asians. This study added important insight into the effect of ethnicity on insulin treatment outcomes in patients with type 2 diabetes. PMID- 27563255 TI - Algorithm linking patients and general practices in Denmark using the Danish National Health Service Register. AB - BACKGROUND: The patient list system in Denmark assigns virtually all residents to a general practice. Nevertheless, historical information on this link between patient and general practice is not readily available for research purposes. OBJECTIVES: To develop, implement, and evaluate the performance of an algorithm linking individual patients to their general practice by using information from the Danish National Health Service Register and the Danish Civil Registration System. MATERIALS AND METHODS: The National Health Service Register contains information on all services provided by general practitioners from 1990 and onward. On the basis of these data and information on migration history and death obtained from the Civil Registration System, we developed an algorithm that allocated patients to a general practice on a monthly basis. We evaluated the performance of the algorithm between 2002 and 2007. During this time period, we had access to information on the link between patients and general practices. Agreement was assessed by the proportion of months for which the algorithm allocated patients to the correct general practice. We also assessed the proportion of all patients in the patient list system for which the algorithm was able to suggest an allocation. RESULTS: The overall agreement between algorithm and patient lists was 98.6%. We found slightly higher agreement for women (98.8%) than for men (98.4%) and lower agreement in the age group 18-34 years (97.1%) compared to all other age groups (>=98.6%). The algorithm had assigned 83% of all patients in the patient list system after 1 year of follow-up, 91% after 2 years of follow-up, and peaked at 94% during the fourth year. CONCLUSION: We developed an algorithm that enables valid and nearly complete linkage between patients and general practices. The algorithm performs better in subgroups of patients with high health care needs. The algorithm constitutes a valuable tool for primary health care research. PMID- 27563256 TI - Adherence to a flexible extended regimen for oral hormonal contraception provided in blister packaging compared with an adherence-supporting digital tablet dispenser: historical comparison of data from two clinical studies. AB - BACKGROUND: The ClykTM digital pill dispenser helps ensure correct and consistent administration of a flexible extended regimen of the combined oral contraceptive, ethinylestradiol (EE) 20 MUg/drospirenone 3 mg (EE/drospirenone ; YAZ((r)) Flex Flex), guiding users through the intake cycle and 4-day pill break and providing visible and acoustic daily reminders when pill intake is due. A study showed that the audible alarm function of the dispenser could help reduce the number of missed pills, but it lacked an appropriate "non-dispenser" group for a meaningful assessment of the impact of the dispenser on adherence. This study indirectly assessed the overall effect of the digital dispenser on adherence by comparing data from a treatment with standard blister packaging. MATERIALS AND METHODS: One year adherence data were compared from two similarly designed, Phase III, open label, randomized trials of EE/drospirenoneFlex. In study 1, women used diary cards to record adherence with EE/drospirenoneFlex dispensed in blister packs (n=640), and in study 2 the dispenser was used with the alarm activated (n=250) or deactivated (n=248) in addition to using diary cards. RESULTS: A mean (+/-SD) of 4.3 (+/-4.24) missed pills over 1 year were recorded in diary cards among women who dispensed their pills from the blister packages (study 1) compared with 1.0 (+/-2.4) recorded by the alarm-activated dispenser (study 2). In study 2, a mean of 1.9 (+/-4.2) missed pills were reported in the diaries over 1 year compared with 4.4 (+/-9.1) from automatic recording by the dispenser (both arms of study 2), indicating underreporting of missed pills in diary cards vs the digital dispenser. Adjusting for this rate of underreporting, an estimated mean of ten pills were missed over 1 year by women using EE/drospirenoneFlex in blister packs, or ten times more than with the digital dispenser with activated acoustic alarm. CONCLUSION: The digital dispenser helps reduce the number of missed pills and increases adherence. PMID- 27563257 TI - Prevalence and associated factors of female genital cutting among young adult females in Jigjiga district, eastern Ethiopia: a cross-sectional mixed study. AB - PURPOSE: The aim of this study was to assess the prevalence and associated factors of female genital cutting (FGC) among young adult (10-24 years of age) females in Jigjiga district, eastern Ethiopia. METHODS: A school-based cross sectional mixed method combining both quantitative and qualitative research methods was employed among 679 randomly selected young adult female students from Jigjiga district, Somali regional state, eastern Ethiopia, from February to March 2014 to assess the prevalence and associated factors with FGC. A pretested structured questionnaire was used to collect data. The qualitative data were collected using focus group discussion. RESULTS: This study depicted that the prevalence of FGC among the respondents was found to be 82.6%. The dominant form of FGC in this study was type I FGC, 265 (49.3%). The majority of the respondents, 575 (88.3%), had good knowledge toward the bad effects of FGC. Four hundred and seven (62.7%) study participants had positive attitude toward FGC discontinuation. Religion, residence, respondents' educational level, maternal education, attitude, and belief in religious requirement were the most significant predictors of FGC. The possible reasons for FGC practice were to keep virginity, improve social acceptance, have better marriage prospects, religious approval, and have hygiene. CONCLUSION: Despite girls' knowledge and attitude toward the bad effects of FGC, the prevalence of FGC was still high. There should be a concerted effort among women, men, religious leaders, and other concerned bodies in understanding and clarifying the wrong attachment between the practice and religion through behavioral change communication and advocacy at all levels. PMID- 27563258 TI - Sildenafil citrate for the management of fetal growth restriction and oligohydramnios. AB - Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full term healthy baby with uneventful neonatal course. PMID- 27563259 TI - Arterial stiffness, as monitored by cardio-ankle vascular index, is affected by obstructive sleep apnea, blood glucose control, and body weight - a case with 8 years follow up. AB - The cardio-ankle vascular index (CAVI) is an indicator of arterial stiffness from the heart to the ankles. The CAVI increases as arteriosclerosis progresses, but it can be decreased by appropriate treatment. There are several risk factors for coronary artery disease, however, the degree of stress caused by each separate risk factor to arteries cannot be assessed. CAVI increases with age and according to the severity of atherosclerosis. We found that CAVI also changes in response to the control of risk factors, which may be associated with the functional stiffness of arteries. CAVI can be a useful indicator of risk control for coronary artery disease. We followed a patient aged 71 years who had diabetes mellitus and obstructive sleep apnea (OSA) by measuring CAVI for 8 years from age 63. He underwent coronary artery bypass grafting due to angina pectoris when he was 63 years old. Before coronary artery bypass grafting, CAVI was 11.8 on the right and 11.5 on the left. Three years later he was found to have OSA and received treatment with continuous positive airway pressure. There was a marked improvement in CAVI after continuous positive airway pressure (age 68; right 10.4, left 10.2). However, following a gradual increase in body weight and worsening of diabetes mellitus, CAVI showed an increasing trend. CAVI decreased with biguanides treatment, but increased again with an increase in body weight. In conclusion, CAVI responded to the patient's conditions including obesity, diabetes mellitus, and OSA. CAVI is not only a marker of arterial stiffness, but can also be a useful indicator of physiological status; it may be effective in total risk control for coronary artery disease. PMID- 27563260 TI - Balancing innovation and medical device regulation: the case of modern metal-on metal hip replacements. AB - Due to problems with wear particle generation and subsequent loosening using conventional metal-on-polyethylene total hip replacements, there has been a shift toward alternative bearing systems, including metal-on-metal (MoM), for younger, more active patients with degenerative joint disease. Based on positive results from early short-term clinical studies, MoM hip replacements were readily adopted by orthopedic surgeons with thousands being implanted worldwide over the past decade. Unacceptably high revision rates reported by two national joint registries called into question the rigorousness of the regulatory approval process for these implants, particularly with respect to premarket data requirements to prove safety, effectiveness, and the appropriateness of the regulatory pathway chosen. The purpose of this review was to investigate the balance between facilitating the introduction of new medical technologies and the need to ensure safety and effectiveness through comprehensive regulatory assessment. The case of MoM hip replacement devices was used to frame the investigation and subsequent discussions. The regulatory approval processes and post-market surveillance requirements associated with three common MoM hip replacements (two resurfacings: the Birmingham and articular surface replacement and the articular surface replacement XL total hip replacement) were investigated. With respect to modern MoM hip replacement devices, the balance between facilitating the introduction of these new medical technologies and the need to ensure safety and effectiveness through comprehensive regulatory assessment was not achieved. The lessons learned from these experiences have application beyond joint replacements to the introduction of new medical technologies in general, particularly for those who have a significant potential for harm. In this regard, a series of recommendations have been developed to contribute to the evolution of the medical device regulatory process. PMID- 27563261 TI - D3D augmented reality imaging system: proof of concept in mammography. AB - PURPOSE: The purpose of this article is to present images from simulated breast microcalcifications and assess the pattern of the microcalcifications with a technical development called "depth 3-dimensional (D3D) augmented reality". MATERIALS AND METHODS: A computer, head display unit, joystick, D3D augmented reality software, and an in-house script of simulated data of breast microcalcifications in a ductal distribution were used. No patient data was used and no statistical analysis was performed. RESULTS: The D3D augmented reality system demonstrated stereoscopic depth perception by presenting a unique image to each eye, focal point convergence, head position tracking, 3D cursor, and joystick fly-through. CONCLUSION: The D3D augmented reality imaging system offers image viewing with depth perception and focal point convergence. The D3D augmented reality system should be tested to determine its utility in clinical practice. PMID- 27563262 TI - Shoulder injuries in soccer goalkeepers: review and development of a FIFA 11+ shoulder injury prevention program. AB - In the last years, shoulder injuries have represented an increasing health problem in soccer players. The goalkeepers are more exposed to shoulder disorders than other field players. Injury prevention exercises for upper limbs were cited in few studies involving throwing athletes, but we know that goalkeepers need a specific program. The purpose of this study is to describe the development of an adapted Federation Internationale de Football Association (FIFA) 11+ program, namely the FIFA 11+ shoulder, which targets the prevention of shoulder injuries in soccer goalkeepers. The FIFA 11+ shoulder program is structured into three parts: general warming-up exercises, exercises to improve strength and balance of the shoulder, elbow, wrist, and finger muscles, and advanced exercises for core stability and muscle control. The exercises were selected based on recommendations from studies demonstrating high electromyographic activity. PMID- 27563263 TI - Factor structure and external correlates of posttraumatic stress disorder symptoms among African American firefighters. AB - This study compared the relative goodness of fit of three well-established factorial models of posttraumatic stress disorder (PTSD) symptoms among 477 African American male firefighters in a large city in the US. The compared models were the two four-factor emotional numbing and dysphoria models and a five-factor dysphoric arousal model. The study also examined the convergent and discriminant validity of PTSD symptom clusters in relation to depression and alcohol dependence symptoms. Both the emotional numbing and dysphoric arousal PTSD models provided a superior fit to the data compared to the dysphoria model. Findings also indicated a good fit for factor models that included PTSD, depression, and alcohol dependence latent factors, which provides support for the specificity of PTSD symptom clusters. Depression symptoms were more strongly correlated with PTSD symptom clusters than alcohol dependence. In the dysphoric arousal model, depression and alcohol dependence were equally related to the emotional numbing and dysphoric arousal clusters; however, both depression and alcohol dependence were more highly correlated with dysphoric arousal than with anxious arousal. Even though the emotional numbing and dysphoric arousal models demonstrated a superior fit to the data, the four-factor dysphoria model may provide a more parsimonious representation of PTSD's latent structure than the five-factor dysphoric arousal model. In conclusion, this study extends support for the well established PTSD symptom factor models among African Americans, a population with whom these models had not been examined earlier. PMID- 27563265 TI - Self-assessment of nursing competency among final year nursing students in Thailand: a comparison between public and private nursing institutions. AB - INTRODUCTION AND OBJECTIVES: Nurses play a major role in Thailand's health care system. In recent years, the production of nurses, in both the public and private sectors, has been growing rapidly to respond to the shortage of health care staff. Alongside concerns over the number of nurses produced, the quality of nursing graduates is of equal importance. This study therefore aimed to 1) compare the self-assessed competency of final year Thai nursing students between public and private nursing schools, and 2) explore factors that were significantly associated with competency level. METHODS: A cross-sectional clustered survey was conducted on 40 Thai nursing schools. Data were collected through self-administered questionnaires. The questionnaire consisted of questions about respondents' background, their education profile, and a self measured competency list. Descriptive statistics, factor analysis, and multivariate regression analysis were applied. RESULTS: A total of 3,349 students participated in the survey. Approximately half of the respondents had spent their childhood in rural areas. The majority of respondents reported being "confident" or "very confident" in all competencies. Private nursing students reported a higher level of "public health competency" than public nursing students with statistical significance. However, there was no significant difference in "clinical competency" between the two groups. CONCLUSION: Nursing students from private institutions seemed to report higher levels of competency than those from public institutions, particularly with regard to public health. This phenomenon might have arisen because private nursing students had greater experience of diverse working environments during their training. One of the key limitations of this study was that the results were based on the subjective self-assessment of the respondents, which might risk respondent bias. Further studies that evaluate current nursing curricula in both public and private nursing schools to assess whether they meet the health needs of the population are recommended. PMID- 27563264 TI - A simple heuristic for Internet-based evidence search in primary care: a randomized controlled trial. AB - BACKGROUND: General practitioners (GPs) are confronted with a wide variety of clinical questions, many of which remain unanswered. METHODS: In order to assist GPs in finding quick, evidence-based answers, we developed a learning program (LP) with a short interactive workshop based on a simple three-step-heuristic to improve their search and appraisal competence (SAC). We evaluated the LP effectiveness with a randomized controlled trial (RCT). Participants (intervention group [IG] n=20; control group [CG] n=31) rated acceptance and satisfaction and also answered 39 knowledge questions to assess their SAC. We controlled for previous knowledge in content areas covered by the test. RESULTS: Main outcome - SAC: within both groups, the pre-post test shows significant (P=0.00) improvements in correctness (IG 15% vs CG 11%) and confidence (32% vs 26%) to find evidence-based answers. However, the SAC difference was not significant in the RCT. OTHER MEASURES: Most workshop participants rated "learning atmosphere" (90%), "skills acquired" (90%), and "relevancy to my practice" (86%) as good or very good. The LP-recommendations were implemented by 67% of the IG, whereas 15% of the CG already conformed to LP recommendations spontaneously (odds ratio 9.6, P=0.00). After literature search, the IG showed a (not significantly) higher satisfaction regarding "time spent" (IG 80% vs CG 65%), "quality of information" (65% vs 54%), and "amount of information" (53% vs 47%). CONCLUSION: Long-standing established GPs have a good SAC. Despite high acceptance, strong learning effects, positive search experience, and significant increase of SAC in the pre-post test, the RCT of our LP showed no significant difference in SAC between IG and CG. However, we suggest that our simple decision heuristic merits further investigation. PMID- 27563266 TI - Local generalised method of moments: an application to point process-based rainfall models. AB - Long series of simulated rainfall are required at point locations for a range of applications, including hydrological studies. Clustered point process-based rainfall models have been used for generating such simulations for many decades. These models suffer from a major limitation, however: their stationarity. Although seasonality can be allowed by fitting separate models for each calendar month or season, the models are unsuitable in their basic form for climate impact studies. In this paper, we develop new methodology to address this limitation. We extend the current fitting approach by allowing the discrete covariate, calendar month, to be replaced or supplemented with continuous covariates that are more directly related to the incidence and nature of rainfall. The covariate-dependent model parameters are estimated for each time interval using a kernel-based nonparametric approach within a generalised method-of-moments framework. An empirical study demonstrates the new methodology using a time series of 5-min rainfall data. The study considers both local mean and local linear approaches. While asymptotic results are included, the focus is on developing useable methodology for a complex model that can only be solved numerically. Issues including the choice of weighting matrix, estimation of parameter uncertainty and bandwidth and model selection are considered from this perspective. (c) 2015 The Authors. Environmetrics Published by John Wiley & Sons Ltd. PMID- 27563267 TI - Validation and comparison of geostatistical and spline models for spatial stream networks. AB - Scientists need appropriate spatial-statistical models to account for the unique features of stream network data. Recent advances provide a growing methodological toolbox for modelling these data, but general-purpose statistical software has only recently emerged, with little information about when to use different approaches. We implemented a simulation study to evaluate and validate geostatistical models that use continuous distances, and penalised spline models that use a finite discrete approximation for stream networks. Data were simulated from the geostatistical model, with performance measured by empirical prediction and fixed effects estimation. We found that both models were comparable in terms of squared error, with a slight advantage for the geostatistical models. Generally, both methods were unbiased and had valid confidence intervals. The most marked differences were found for confidence intervals on fixed-effect parameter estimates, where, for small sample sizes, the spline models underestimated variance. However, the penalised spline models were always more computationally efficient, which may be important for real-time prediction and estimation. Thus, decisions about which method to use must be influenced by the size and format of the data set, in addition to the characteristics of the environmental process and the modelling goals. (c)2015 The Authors. Environmetrics published by John Wiley & Sons, Ltd. PMID- 27563268 TI - A new species of Ceratoteleas Kozlov (Hymenoptera, Scelionidae) from Japan, with a description of the male of Ceratoteleas. AB - Ceratoteleas cornus sp. n. is described from Japan. The male of the genus is described for the first time. PMID- 27563269 TI - Calosoma aethiops (Jeannel, 1940) as a new synonym of Calosoma imbricatum hottentotum Chaudoir, 1852, a new status of Calosoma roeschkei Breuning, 1927, and a revision of the Calosoma senegalense group sensu Hackel, 2012 (Coleoptera, Carabidae, Carabini). AB - Calosoma aethiops (Jeannel, 1940) as a new synonym of Calosoma imbricatum hottentotum Chaudoir, 1852, a new status of Calosoma roeschkei Breuning, 1927, and a revision of the Calosoma senegalense group sensu Hackel, 2012 (Coleoptera: Carabidae: Carabini). Conducted is a taxonomic revision of the Calosoma senegalense group sensu Hackel, 2012. Placed in the group sensu stricto are four species: Calosoma planicolle Chaudoir, 1869, Calosoma scabrosum Chaudoir, 1843, Calosoma senegalense Dejean, 1831, and Ctenosta strandi Breuning, 1934. Calosoma aethiops Jeannel, 1940 is synonymized with Calosoma imbricatum hottentotum Chaudoir, 1852, and Calosoma roeschkei Breuning, 1927 is newly regarded as a subspecies of Calosoma scabrosum. The taxonomic conclusions are based on morphometry of the holotypes and 10 male and 10 female specimens of each taxon, and on morphology of the aedeagus including inflated endophalus. PMID- 27563270 TI - Three new species of the subgenus Leipopleura Seidlitz from Tibet, China (Coleoptera, Tenebrionidae, Bioramix Bates). AB - Three new species of darkling beetles (Tenebrionidae) belonging to the subgenus Leipopleura of the genus Bioramix Bates, 1879, Bioramix (Leipopleura) baqenensis Li & Egorov, sp. n., Bioramix (Leipopleura) nyainrongensis Li & Egorov, sp. n., and Bioramix (Leipopleura) banbarensis Li & Egorov, sp. n. are described from the Tibet Autonomous Region in China. Additionally, a new identification key is provided to all known Chinese representatives of the subgenus Leipopleura. PMID- 27563271 TI - Revision of the genus Ptomaphagus Hellwig (Coleoptera, Leiodidae, Cholevinae) from Taiwan Island. AB - Ptomaphagus (s. str.) chenggongi sp. n. and Ptomaphagus (s. str.) tingtingae sp. n. (Coleoptera, Leiodidae, Cholevinae, Ptomaphagini) are described from Taiwan Island. In addition, a new subjective synonym is proposed, Ptomaphagus (s. str.) yasutoshii Nishikawa, 1993 = Ptomaphagus (s. str.) smetanai Perreau, 1996, syn. n. Relevant morphological characters of the examined Ptomaphagus species are illustrated with colour plates, and their known distributions are mapped. PMID- 27563272 TI - A new species of the genus Falsoibidion Pic (Coleoptera, Cerambycidae) from Korea. AB - A new species of the genus Falsoibidion Pic, 1922 (Coleoptera, Cerambycidae, Cerambycinae, Callidiopini) from Korea is described. Habitus and genitalia of male and female of the new species are illustrated. PMID- 27563273 TI - Herniosina Rohacek: revised concept, two new species, new key and atlas of male and female terminalia (Diptera, Sphaeroceridae). AB - The taxonomic concept of Herniosina Rohacek, 1983 (Diptera: Sphaeroceridae) is revised on the basis of five W. Palaearctic species, thus excluding the E. Nearctic Herniosina voluminosa Marshall, 1987 whose inclusion caused the paraphyly of the genus. Two new species, Herniosina erymantha sp. n. (male only, Greece: Peloponnese) and Herniosina hamata sp. n. (both sexes, Cyprus), are described and illustrated, and the other three species, Herniosina bequaerti (Villeneuve, 1917), Herniosina horrida (Rohacek, 1978) and Herniosina pollex Rohacek, 1993, are diagnosed with an atlas of their male and female terminalia. The relationships of the redefined genus and of all its species are discussed, and their biology and distribution are reviewed. A new illustrated key to Herniosina species is given. PMID- 27563274 TI - Molecular phylogeny of the forensically important genus Cochliomyia (Diptera: Calliphoridae). AB - Cochliomyia Townsend includes several abundant and one of the most broadly distributed, blow flies in the Americas, and is of significant economic and forensic importance. For decades, Cochliomyia hominivorax (Coquerel) and Cochliomyia macellaria (Fabricius) have received attention as livestock parasites and primary indicator species in forensic entomology. However, Cochliomyia minima Shannon and Cochliomyia aldrichi Del Ponte have only been subject to basic taxonomy and faunistic studies. Here we present the first complete phylogeny of Cochliomyia including numerous specimens per species, collected from 13 localities in the Caribbean. Four genes, the mitochondrial COI and the nuclear EF 1alpha, 28S rRNA, and ITS2, were analyzed. While we found some differences among gene trees, a concatenated gene matrix recovered a robustly supported monophyletic Cochliomyia with Compsomyiops Townsend as its sister group and recovered the monophyly of Cochliomyia hominivorax, Cochliomyia macellaria and Cochliomyia minima. Our results support a close relationship between Cochliomyia minima and Cochliomyia aldrichi. However, we found Cochliomyia aldrichi containing Cochliomyia minima, indicating recent speciation, or issues with the taxonomy of the group. We provide basic information on habitat preference, distribution and feeding habits of Cochliomyia minima and Cochliomyia aldrichi that will be useful for future forensic studies in the Caribbean. PMID- 27563275 TI - Taxonomic notes on the genus Orthobrachia Warren, with description of a new species from China and Thailand (Lepidoptera, Geometridae). AB - All seven members of the genus Orthobrachia Warren, 1895 are recorded, with description of a new species from Sichuan Province, China and N. Thailand, including Orthobrachia latifasciata (Moore, 1888) and Orthobrachia flavidior (Hampson, 1898) from northern India, Nepal and China, Orthobrachia tenebrosa Yazaki, 1992 from Nepal and India, Orthobrachia owadai Yazaki, 1992 from India, Orthobrachia simpliciata Yazaki, 2002 from China, and Orthobrachia maoershanensis Huang, Xin & Wang, 2003 from South China. A key to the Orthobrachia species is provided, along with a distributional map of all nominal species. The type specimens of the new species are deposited in Hunan Agricultural University (China), South China Agricultural University (China) and Zoological Research Museum Alexander Koenig (Germany). PMID- 27563276 TI - Corrigenda: Cesar Marcial Escobedo-Bonilla, Jose Luis Ibarra Rangel (2014) Susceptibility to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV) in three batches of whiteleg shrimp Litopenaeus vannamei (Boone, 1931). ZooKeys 457: 355-365. doi: 10.3897/zookeys.457.6715. AB - [This corrects the article DOI: 10.3897/zookeys.457.6715.]. PMID- 27563277 TI - Two new species of Prionomastix Mayr (Hymenoptera: Encyrtidae) with a key to Indian species. AB - BACKGROUND: Species of Prionomastix Mayr were not known from India when Manickavasagam and Rameshkumar 2011 and Rameshkumar and Poorani 2015 misidentified a new species as P. siccarius. Now it is corrected by explaining the characters as to why it is new and not P. siccarius along with another new species. As we have one another new species, P. orientialis, described by Rameshkumar and Poorani 2015 our two new species are compared with P. orientalis also. NEW INFORMATION: Two new species of Prionomastix Mayr (Hymenoptera: Encyrtidae), one from Bihar state and the other from Tamil Nadu state, India, are described viz., P. tamilnadensis sp. nov and P. biharensis sp. nov. and a key to all known Indian species is provided. PMID- 27563278 TI - Quantitative Mapping of Stress Heterogeneity in Polycrystalline Alumina using Hyperspectral Fluorescence Microscopy. AB - The microstructurally-induced heterogeneous stress fields arising in a series of Cr-doped polycrystalline alumina materials are mapped with sub-micrometer sub grain size resolution using fluorescence microscopy. Analysis of the hyperspectral data sets generated during imaging enabled both the amplitude and position of the characteristic Cr R1 fluorescence peak to be determined at every pixel in an image. The peak amplitude information was used to segment the images into individual grains and grain boundary regions. The peak position information, in conjunction with measurements on single-crystal controls, was used to quantify overall stress distributions in the materials and provide stress scales for maps. The combined information enabled spatial variations in the stress fields in crystallographic axes to be mapped and compared directly with microstructural features such as grains and grain boundaries. The mean c-axis stresses in these materials were approximately 200 MPa with stress distribution widths of about 70 MPa, both increasing with average grain size. Greatest variations in stress were observed at grain junctions; no trend in the stress for individual grains with grain size was observed. PMID- 27563279 TI - It is difficult to tell if there is a Condorcet spanning tree. AB - We apply the well-known Condorcet criterion from voting theory outside of its classical framework and link it with spanning trees of an undirected graph. In situations in which a network, represented by a spanning tree of an undirected graph, needs to be installed, decision-makers typically do not agree on the network to be implemented. Instead, each of these decision-makers has her own ideal conception of the network. In order to derive a group decision, i.e., a single spanning tree for the entire group of decision-makers, the goal would be a spanning tree that beats each other spanning tree in a simple majority comparison. When comparing two dedicated spanning trees, a decision-maker will be considered to be more satisfied with the one that is "closer" to her proposal. In this context, the most basic and natural measure of distance is the usual set difference: we simply count the number of edges the spanning tree has in common with the proposal of the decision-maker. In this work, we show that it is computationally intractable to decide (1) if such a spanning tree exists, and (2) if a given spanning tree satisfies the Condorcet criterion. PMID- 27563280 TI - Likelihood-free simulation-based optimal design with an application to spatial extremes. AB - In this paper we employ a novel method to find the optimal design for problems where the likelihood is not available analytically, but simulation from the likelihood is feasible. To approximate the expected utility we make use of approximate Bayesian computation methods. We detail the approach for a model on spatial extremes, where the goal is to find the optimal design for efficiently estimating the parameters determining the dependence structure. The method is applied to determine the optimal design of weather stations for modeling maximum annual summer temperatures. PMID- 27563281 TI - Ambiguous participation in older hospitalized patients: gaining influence through active and passive approaches-a qualitative study. AB - BACKGROUND: Patient participation is required by law in Norway and in several western countries. Current participation ideology is based on individualism, which may conflict with the older generation's commonly held values of solidarity and community. Hence, different values and ideologies may come in conflict when older patients receive treatment and rehabilitation in geriatric wards. Participation is a guiding principle in rehabilitation. Criteria for admission of older patients to geriatric wards are complex health problems, acute illness and/or acute physical and/or cognitive functional failure. The ideal is an active and engaged patient. The aim of the study was to describe the difficulties experienced by older patients on acute geriatric wards when involving themselves with their own treatment and care. METHODS: In this qualitative study older patients were interviewed during hospitalization in geriatric wards and asked to tell about their experiences with participation. Data analysis was conducted using a phenomenological hermeneutic method. RESULTS: The patients experienced difficulties in participating in decisions and care. They linked their difficulties to their own diminishing capabilities, and cited the ward's busy schedule as a reason for abstaining from participation. However, despite their reservations, they did participate in decisions in different ways. Their participatory practices appeared ambiguous and they employed various strategies to put themselves in a position of influence. The most important of these involved their relatives. The patients delegated to family the tasks of seeking, receiving and giving information to the nurses and the staff, and, to some extent, for the dialogues with hospital staff about their needs and plan of care. The family appeared to accept the responsibility willingly. CONCLUSIONS: The patients addressed their difficulties by authorizing family members to act and participate on their behalf. This underlines the family's important role in patient participation and the role that nurses and other staff must play in collaborating with the patient and their family to facilitate participation independently of the patients' performances of participation. PMID- 27563283 TI - The Transition from Animal to Linguistic Communication. AB - Darwin's theory predicts that linguistic behavior gradually evolved out of animal forms of communication (signaling). However, this prediction is confronted by the conceptual problem that there is an essential difference between signaling and linguistic behavior: using words is a normative practice. It is argued that we can resolve this problem if we (1) note that language evolution is the outcome of an evolutionary transition, and (2) observe that the use of words evolves during ontogenesis out of babbling. It is discussed that language evolved as the result of an expansion of the vocalizing powers of our ancestors. This involved an increase in the volitional control of our speech apparatus (leading to the ability to produce new combinations of vowels and consonants), but also the evolution of socially guided learning. It resulted in unique human abilities, namely doing things with words and later reasoning and giving reasons. PMID- 27563282 TI - Acidification changes affect the inflammasome in human nucleus pulposus cells. AB - BACKGROUND: Interleukin (IL)-1beta is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1beta is present in cells in an inactive form (pro-IL-1beta). However, under pathological conditions, pro-IL 1beta is turned into its active form (IL-1beta) by the inflammasome, a multi protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored. METHODS: Here we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture. RESULTS: In this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL 1beta. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1beta. CONCLUSIONS: Taken together, these findings suggest that the inflammatory response through IL-1beta experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification. PMID- 27563284 TI - Ethics in Community-University-Artist Partnered Research: Tensions, Contradictions and Gaps Identified in an 'Arts for Social Change' Project. AB - Academics from diverse disciplines are recognizing not only the procedural ethical issues involved in research, but also the complexity of everyday "micro" ethical issues that arise. While ethical guidelines are being developed for research in aboriginal populations and low-and-middle-income countries, multi partnered research initiatives examining arts-based interventions to promote social change pose a unique set of ethical dilemmas not yet fully explored. Our research team, comprising health, education, and social scientists, critical theorists, artists and community-activists launched a five-year research partnership on arts-for-social change. Funded by the Social Science and Humanities Research Council in Canada and based in six universities, including over 40 community-based collaborators, and informed by five main field projects (circus with street youth, theatre by people with disabilities, dance for people with Parkinson's disease, participatory theatre with refugees and artsinfused dialogue), we set out to synthesize existing knowledge and lessons we learned. We summarized these learnings into 12 key points for reflection, grouped into three categories: community-university partnership concerns (n = 3), dilemmas related to the arts (n = 5), and team issues (n = 4). In addition to addressing previous concerns outlined in the literature (e.g., related to consent, anonymity, dangerous emotional terrain, etc.), we identified power dynamics (visible and hidden) hindering meaningful participation of community partners and university based teams that need to be addressed within a reflective critical framework of ethical practice. We present how our team has been addressing these issues, as examples of how such concerns could be approached in community-university partnerships in arts for social change. PMID- 27563285 TI - Experiences of COPD patients with existing smoking cessation programs and their preferences for improvement - a qualitative analysis. AB - BACKGROUND: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). For current smokers who are diagnosed with COPD, their first treatment option is to stop smoking. Motivation is necessary for long-term smoking cessation; therefore, when designing smoking cessation programs, the patients' needs and preferences should be considered. We focused on COPD patients' experiences with existing smoking cessation programs and evaluated their preferences for the improvement of these programs. METHODS: We conducted 18 guideline-based interviews with COPD patients between April and June 2014 in Germany. Each patient with COPD, who was a current or past smoker and had made at least one attempt to quit smoking in the past 5 years, was included in the study. We audiotaped, verbatim transcribed, and evaluated the interviews, using content analysis. RESULTS: The patients had broad and different experiences with pharmaceutical, behavioral, and alternative approaches that supported or negatively influenced the smoking cessation process. Pharmaceuticals were viewed as an expensive alternative with many side effects although they helped to stop cravings for a few moments. Furthermore, the bad structure and impersonal content of the seminars for smoking cessation negatively influenced group cohesion, and therefore degrading the patients' motivation to stop smoking. Alternative methods, such as acupuncture and hypnosis were mostly ineffective in smoking cessation, but in some cases, served as motivational strategies. CONCLUSION: Negative experiences with smoking cessation were explained by the patients' lack of motivation or resolution. Other negative experiences, such as the structure of seminars for smoking cessation and the high price of pharmaceuticals should be addressed through policy changes to increase the patients' motivation to quit smoking. PMID- 27563287 TI - The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice. AB - Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID- 27563286 TI - Organization of the Zone of Transition between the Pretectum and the Thalamus, with Emphasis on the Pretectothalamic Lamina. AB - The zone of transition between the pretectum, derived from prosomere 1, and the thalamus, derived from prosomere 2, is structurally complex and its understanding has been hampered by cytoarchitectural and terminological confusion. Herein, using a battery of complementary morphological approaches, including cytoarchitecture, myeloarchitecture and the expression of molecular markers, we pinpoint the features or combination of features that best characterize each nucleus of the pretectothalamic transitional zone of the rat. Our results reveal useful morphological criteria to identify and delineate, with unprecedented precision, several [mostly auditory] nuclei of the posterior group of the thalamus, namely the pretectothalamic lamina (PTL; formerly known as the posterior limitans nucleus), the medial division of the medial geniculate body (MGBm), the suprageniculate nucleus (SG), and the ethmoid, posterior triangular and posterior nuclei of the thalamus. The PTL is a sparsely-celled and fiber rich flattened nucleus apposed to the lateral surface of the anterior pretectal nucleus (APT) that marks the border between the pretectum and the thalamus; this structure stains selectively with the Wisteria floribunda agglutinin (WFA), and is essentially immunonegative for the calcium binding protein parvalbumin (PV). The MGBm, located medial to the ventral division of the MGB (MGBv), can be unequivocally identified by the large size of many of its neurons, its dark immunostaining for PV, and its rather selective staining for WFA. The SG, which extends for a considerable caudorostral distance and deviates progressively from the MGB, is characterized by its peculiar cytoarchitecture, the paucity of myelinated fibers, and the conspicuous absence of staining for calretinin (CR); indeed, in many CR-stained sections, the SG stands out as a blank spot. Because most of these nuclei are small and show unique anatomical relationships, the information provided in this article will facilitate the interpretation of the results of experimental manipulations aimed at the auditory thalamus and improve the design of future investigations. Moreover, the previously neglected proximity between the MGBm and the caudal region of the scarcely known PTL raises the possibility that certain features or roles traditionally attributed to the MGBm may actually belong to the PTL. PMID- 27563289 TI - MINC 2.0: A Flexible Format for Multi-Modal Images. AB - It is often useful that an imaging data format can afford rich metadata, be flexible, scale to very large file sizes, support multi-modal data, and have strong inbuilt mechanisms for data provenance. Beginning in 1992, MINC was developed as a system for flexible, self-documenting representation of neuroscientific imaging data with arbitrary orientation and dimensionality. The MINC system incorporates three broad components: a file format specification, a programming library, and a growing set of tools. In the early 2000's the MINC developers created MINC 2.0, which added support for 64-bit file sizes, internal compression, and a number of other modern features. Because of its extensible design, it has been easy to incorporate details of provenance in the header metadata, including an explicit processing history, unique identifiers, and vendor-specific scanner settings. This makes MINC ideal for use in large scale imaging studies and databases. It also makes it easy to adapt to new scanning sequences and modalities. PMID- 27563288 TI - Short-Term High-Fat Diet (HFD) Induced Anxiety-Like Behaviors and Cognitive Impairment Are Improved with Treatment by Glyburide. AB - Obesity-associated comorbidities such as cognitive impairment and anxiety are increasing public health burdens that have gained prevalence in children. To better understand the impact of childhood obesity on brain function, mice were fed with a high-fat diet (HFD) from weaning for 1, 3 or 6 weeks. When compared to low-fat diet (LFD)-fed mice (LFD-mice), HFD-fed mice (HFD-mice) had impaired novel object recognition (NOR) after 1 week. After 3 weeks, HFD-mice had impaired NOR and object location recognition (OLR). Additionally, these mice displayed anxiety-like behavior by measure of both the open-field and elevated zero maze (EZM) testing. At 6 weeks, HFD-mice were comparable to LFD-mice in NOR, open field and EZM performance but they remained impaired during OLR testing. Glyburide, a second-generation sulfonylurea for the treatment of type 2 diabetes, was chosen as a countermeasure based on previous data exhibiting its potential as an anxiolytic. Interestingly, a single dose of glyburide corrected deficiencies in NOR and mitigated anxiety-like behaviors in mice fed with HFD-diet for 3 weeks. Taken together these results indicate that a HFD negatively impacts a subset of hippocampal-independent behaviors relatively rapidly, but such behaviors normalize with age. In contrast, impairment of hippocampal-sensitive memory takes longer to develop but persists. Since single-dose glyburide restores brain function in 3-week-old HFD-mice, drugs that block ATP-sensitive K(+) (KATP) channels may be of clinical relevance in the treatment of obesity-associated childhood cognitive issues and psychopathologies. PMID- 27563290 TI - Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson's Disease? AB - BACKGROUND: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson's disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. OBJECTIVE: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD. METHODS: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1-normal cognition (score 27-30), group 2-mild cognitive impairment (score 21-26), group 3-moderate or severe cognitive impairment (score <= 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score >=13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS). RESULTS: All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score. CONCLUSIONS: Patients gain benefit in the rehabilitative outcomes, regardless of cognition. Our data suggest that rehabilitation could be effective also in Parkinsonian subjects with cognitive impairment, as well as with dysexecutive syndrome. PMID- 27563292 TI - The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes. AB - Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90 min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically. PMID- 27563293 TI - Autism and Classical Eyeblink Conditioning: Performance Changes of the Conditioned Response Related to Autism Spectrum Disorder Diagnosis. AB - Changes in the timing performance of conditioned responses (CRs) acquired during trace and delay eyeblink conditioning (EBC) are presented for diagnostic subgroups of children having autism spectrum disorder (ASD) aged 6-15 years. Children diagnosed with autistic disorder (AD) were analyzed separately from children diagnosed with either Asperger's syndrome or Pervasive developmental disorder (Asp/PDD) not otherwise specified and compared to an age- and IQ-matched group of children who were typically developing (TD). Within-subject and between groups contrasts in CR performance on sequential exposure to trace and delay EBC were analyzed to determine whether any differences would expose underlying functional heterogeneities of the cerebral and cerebellar systems, in ASD subgroups. The EBC parameters measured were percentage CRs, CR onset latency, and CR peak latency. Neither AD nor Asp/PDD groups were impaired in CR acquisition during trace or delay EBC. Both AD and Asp/PDD altered CR timing, but not always in the same way. Although the AD group showed normal CR timing during trace EBC, the Asp/PDD group showed a significant 27 and 28 ms increase in CR onset and peak latency, respectively, during trace EBC. In contrast, the direction of the timing change was opposite during delay EBC, during which the Asp/PDD group showed a significant 29 ms decrease in CR onset latency and the AD group showed a larger 77 ms decrease in CR onset latency. Only the AD group showed a decrease in CR peak latency during delay EBC, demonstrating another difference between AD and Asp/PDD. The difference in CR onset latency during delay EBC for both AD and Asp/PDD was due to an abnormal prevalence of early onset CRs that were intermixed with CRs having normal timing, as observed both in CR onset histograms and mean CR waveforms. In conclusion, significant heterogeneity in EBC performance was apparent between diagnostic groups, and this may indicate that EBC performance can report the heterogeneity in the neurobiological predispositions for ASD. The findings will inform further explorations with larger cohorts, different sensory modalities, and different EBC paradigms and provide a reference set for future EBC studies of children having ASD and non-human models. PMID- 27563291 TI - Chocolate, Air Pollution and Children's Neuroprotection: What Cognition Tools should be at Hand to Evaluate Interventions? AB - Millions of children across the world are exposed to multiple sources of indoor and outdoor air pollutants, including high concentrations of fine particulate matter (PM2.5) and ozone (O3). The established link between exposure to PM2.5, brain structural, volumetric and metabolic changes, severe cognitive deficits (1.5-2 SD from average IQ) in APOE 4 heterozygous females with >75 - < 94% BMI percentiles, and the presence of Alzheimer's disease (AD) hallmarks in urban children and young adults necessitates exploration of ways to protect these individuals from the deleterious neural effects of pollution exposure. Emerging research suggests that cocoa interventions may be a viable option for neuroprotection, with evidence suggesting that early cocoa interventions could limit the risk of cognitive and developmental concerns including: endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, and metabolic detrimental brain effects. Currently, however, it is not clear how early we should implement consumption of cocoa to optimize its neuroprotective effects. Moreover, we have yet to identify suitable instruments for evaluating cognitive responses to these interventions in clinically healthy children, teens, and young adults. An approach to guide the selection of cognitive tools should take into account neuropsychological markers of cognitive declines in patients with Alzheimer's neuropathology, the distinct patterns of memory impairment between early and late onset AD, and the key literature associating white matter integrity and poor memory binding performance in cases of asymptomatic familial AD. We highlight potential systemic and neural benefits of cocoa consumption. We also highlight Working Memory Capacity (WMC) and attention control tasks as opened avenues for exploration in the air pollution scenario. Exposures to air pollutants during brain development have serious brain consequences in the short and long term and reliable cognition tools should be at hand to evaluate interventions. PMID- 27563294 TI - An Observational Investigation of Behavioral Contagion in Common Marmosets (Callithrix jacchus): Indications for Contagious Scent-Marking. AB - Behavioral contagion is suggested to promote group coordination that may facilitate activity transitions, increased vigilance, and state matching. Apart from contagious yawning, however, very little attention has been given to this phenomenon, and studies on contagious yawning in primates have so far only focused on Old World monkeys and apes. Here we studied behavioral contagion in common marmosets, a species for which group coordination and vigilance are paramount. In particular, we investigated the contagiousness of yawning, stretching, scratching, tongue protrusion, gnawing, and scent-marking. We coded these behaviors from 14 adult marmosets, from two different social groups. During testing sessions, animals were separated into groups of four individuals for 20 min observation periods, across three distinct diurnal time points (morning, midday, and afternoon) to test for circadian patterns. We observed almost no yawning (0.12 yawns/h) and very little stretching behavior. For all other behaviors, which were more common, we found several temporal and inter-individual differences (i.e., sex, age, dominance status) predictive of these responses. Moreover, we found that gnawing and scent-marking, which almost always co occurred as a fixed-action pattern, were highly temporally clustered within observation sessions. We discuss the relative absence of yawning in marmosets as well as the possible function of contagious scent-marking, and provide suggestions for future research into the proximate and ultimate functions of these behaviors in marmosets. PMID- 27563295 TI - The Development of a Bi-Lingual Assessment Instrument to Measure Agentic and Communal Consumer Motives in English and French. AB - Consumer behavior is driven, in part, by the degree to which goods and services appeal to underlying motives for agency and communion. The purpose of this research was to develop a brief individual differences measure of these motivations for use in behavioral research and theoretical and applied consumer psychology and marketing studies. We employed a bi-lingual scale development procedure to create the 10-item Agentic and Communal Consumer Motivation Inventory (ACCMI) in English and French. Two studies show that the ACCMI is language invariant, demonstrates convergent and discriminant validity with consumer, motivational, and interpersonal constructs, and predicts evaluations of products described in agentic and communal terms, respectively, in both languages. The general conclusion of this research is that agency and communion provide a useful framework for understanding and studying consumer buying motivations. Discussion focuses on the relevance of motivational factors for studying human behavior and the applied utility of the ACCMI. PMID- 27563297 TI - Is There an Increased Risk for Ischemic Stroke in Patients with Multiple Sclerosis, and If So, Should Preventive Treatment Be Considered? PMID- 27563296 TI - Effects of Physical Rehabilitation Integrated with Rhythmic Auditory Stimulation on Spatio-Temporal and Kinematic Parameters of Gait in Parkinson's Disease. AB - Movement rehabilitation by means of physical therapy represents an essential tool in the management of gait disturbances induced by Parkinson's disease (PD). In this context, the use of rhythmic auditory stimulation (RAS) has been proven useful in improving several spatio-temporal parameters, but concerning its effect on gait patterns, scarce information is available from a kinematic viewpoint. In this study, we used three-dimensional gait analysis based on optoelectronic stereophotogrammetry to investigate the effects of 5 weeks of supervised rehabilitation, which included gait training integrated with RAS on 26 individuals affected by PD (age 70.4 +/- 11.1, Hoehn and Yahr 1-3). Gait kinematics was assessed before and at the end of the rehabilitation period and after a 3-month follow-up, using concise measures (Gait Profile Score and Gait Variable Score, GPS and GVS, respectively), which are able to describe the deviation from a physiologic gait pattern. The results confirm the effectiveness of gait training assisted by RAS in increasing speed and stride length, in regularizing cadence and correctly reweighting swing/stance phase duration. Moreover, an overall improvement of gait quality was observed, as demonstrated by the significant reduction of the GPS value, which was created mainly through significant decreases in the GVS score associated with the hip flexion-extension movement. Future research should focus on investigating kinematic details to better understand the mechanisms underlying gait disturbances in people with PD and the effects of RAS, with the aim of finding new or improving current rehabilitative treatments. PMID- 27563298 TI - Degradation of Zearalenone by Essential Oils under In vitro Conditions. AB - Essential oils are volatile compounds, extracted from plants, which have a strong odor. These compounds are known for their antibacterial and antifungal properties. However, data concerning degradation of mycotoxins by these metabolites are very limited. The aim of the present study was to investigate the effect of essential oils (cedarwood, cinnamon leaf, cinnamon bark, white grapefruit, pink grapefruit, lemon, eucalyptus, palmarosa, mint, thymic, and rosemary) on zearalenone (ZEA) reduction under various in vitro conditions, including the influence of temperature, pH, incubation time and mycotoxin and essential oil concentrations. The degree of ZEA reduction was determined by HPLC method. It was found that the kind of essential oil influences the effectiveness of toxin level reduction, the highest being observed for lemon, grapefruit, eucalyptus and palmarosa oils, while lavender, thymic and rosemary oils did not degrade the toxin. In addition, the decrease in ZEA content was temperature, pH as well as toxin and essential oil concentration dependent. Generally, higher reduction was observed at higher temperature in a wide range of pH, with clear evidence that the degradation rate increased gradually with time. In some combinations (e.g., palmarosa oil at pH 6 and 4 or 20 degrees C) a toxin degradation rate higher than 99% was observed. It was concluded that some of the tested essential oils may be effective in detoxification of ZEA. We suggested that essential oils should be recognized as an interesting and effective means of ZEA decontamination and/or detoxification. PMID- 27563299 TI - Mycorrhizal Symbiotic Efficiency on C3 and C4 Plants under Salinity Stress - A Meta-Analysis. AB - A wide range of C3 and C4 plant species could acclimatize and grow under the impact of salinity stress. Symbiotic relationship between plant roots and arbuscular mycorrhizal fungi (AMF) are widespread and are well known to ameliorate the influence of salinity stress on agro-ecosystem. In the present study, we sought to understand the phenomenon of variability on AMF symbiotic relationship on saline stress amelioration in C3 and C4 plants. Thus, the objective was to compare varied mycorrhizal symbiotic relationship between C3 and C4 plants in saline conditions. To accomplish the above mentioned objective, we conducted a random effects models meta-analysis across 60 published studies. An effect size was calculated as the difference in mycorrhizal responses between the AMF inoculated plants and its corresponding control under saline conditions. Responses were compared between (i) identity of AMF species and AMF inoculation, (ii) identity of host plants (C3 vs. C4) and plant functional groups, (iii) soil texture and level of salinity and (iv) experimental condition (greenhouse vs. field). Results indicate that both C3 and C4 plants under saline condition responded positively to AMF inoculation, thereby overcoming the predicted effects of symbiotic efficiency. Although C3 and C4 plants showed positive effects under low (EC < 4 ds/m) and high (>8 ds/m) saline conditions, C3 plants showed significant effects for mycorrhizal inoculation over C4 plants. Among the plant types, C4 annual and perennial plants, C4 herbs and C4 dicot had a significant effect over other counterparts. Between single and mixed AMF inoculants, single inoculants Rhizophagus irregularis had a positive effect on C3 plants whereas Funneliformis mosseae had a positive effect on C4 plants than other species. In all of the observed studies, mycorrhizal inoculation showed positive effects on shoot, root and total biomass, and in nitrogen, phosphorous and potassium (K) uptake. However, it showed negative effects in sodium (Na) uptake in both C3 and C4 plants. This influence, owing to mycorrhizal inoculation, was significantly higher in K uptake in C4 plants. For our analysis, we concluded that AMF inoculated C4 plants showed more competitive K(+) ions uptake than C3 plants. Therefore, maintenance of high cytosolic K(+)/Na(+) ratio is a key feature of plant salt tolerance. Studies on the detailed mechanism for the selective transport of K in C3 and C4 mycorrhizal plants under salt stress is lacking, and this needs to be explored. PMID- 27563300 TI - High Heating Rates Affect Greatly the Inactivation Rate of Escherichia coli. AB - Heat resistance of microorganisms can be affected by different influencing factors. Although, the effect of heating rates has been scarcely explored by the scientific community, recent researches have unraveled its important effect on the thermal resistance of different species of vegetative bacteria. Typically heating rates described in the literature ranged from 1 to 20 degrees C/min but the impact of much higher heating rates is unclear. The aim of this research was to explore the effect of different heating rates, such as those currently achieved in the heat exchangers used in the food industry, on the heat resistance of Escherichia coli. A pilot plant tubular heat exchanger and a thermoresistometer Mastia were used for this purpose. Results showed that fast heating rates had a deep impact on the thermal resistance of E. coli. Heating rates between 20 and 50 degrees C/min were achieved in the heat exchanger, which were much slower than those around 20 degrees C/s achieved in the thermoresistometer. In all cases, these high heating rates led to higher inactivation than expected: in the heat exchanger, for all the experiments performed, when the observed inactivation had reached about seven log cycles, the predictions estimated about 1 log cycle of inactivation; in the thermoresistometer these differences between observed and predicted values were even more than 10 times higher, from 4.07 log cycles observed to 0.34 predicted at a flow rate of 70 mL/min and a maximum heating rate of 14.7 degrees C/s. A quantification of the impact of the heating rates on the level of inactivation achieved was established. These results point out the important effect that the heating rate has on the thermal resistance of E. coli, with high heating rates resulting in an additional sensitization to heat and therefore an effective food safety strategy in terms of food processing. PMID- 27563301 TI - Antibody-Dependent NK Cell Activation Is Associated with Late Kidney Allograft Dysfunction and the Complement-Independent Alloreactive Potential of Donor Specific Antibodies. AB - Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1(+) cytotoxic granules, resulting from the recognition of rituximab coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1 year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of immunosuppressive treatments, robust ADCC responsiveness can be maintained in some KTRs. Because it evaluates both the Fab recognition of alloantigens and Fc-driven NK cell activation, the NK-CHAT represents a potentially valuable tool for the non-invasive and individualized evaluation of humoral risk during transplantation. PMID- 27563302 TI - Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable! AB - Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials. PMID- 27563303 TI - Alternative Oxidase Gene Family in Hypericum perforatum L.: Characterization and Expression at the Post-germinative Phase. AB - Alternative oxidase (AOX) protein is located in the inner mitochondrial membrane and is encoded in the nuclear genome being involved in plant response upon a diversity of environmental stresses and also in normal plant growth and development. Here we report the characterization of the AOX gene family of Hypericum perforatum L. Two AOX genes were identified, both with a structure of four exons (HpAOX1, acc. KU674355 and HpAOX2, acc. KU674356). High variability was found at the N-terminal region of the protein coincident with the high variability identified at the mitochondrial transit peptide. In silico analysis of regulatory elements located at intronic regions identified putative sequences coding for miRNA precursors and trace elements of a transposon. Simple sequence repeats were also identified. Additionally, the mRNA levels for the HpAOX1 and HpAOX2, along with the ones for the HpGAPA (glyceraldehyde-3-phosphate dehydrogenase A subunit) and the HpCAT1 (catalase 1), were evaluated during the post-germinative development. Gene expression analysis was performed by RT-qPCR with accurate data normalization, pointing out HpHYP1 (chamba phenolic oxidative coupling protein 1) and HpH2A (histone 2A) as the most suitable reference genes (RGs) according to GeNorm algorithm. The HpAOX2 transcript demonstrated larger stability during the process with a slight down-regulation in its expression. Contrarily, HpAOX1 and HpGAPA (the corresponding protein is homolog to the chloroplast isoform involved in the photosynthetic carbon assimilation in other plant species) transcripts showed a marked increase, with a similar expression pattern between them, during the post-germinative development. On the other hand, the HpCAT1 (the corresponding protein is homolog to the major H2O2-scavenging enzyme in other plant species) transcripts showed an opposite behavior with a down-regulation during the process. In summary, our findings, although preliminary, highlight the importance to investigate in more detail the participation of AOX genes during the post-germinative development in H. perforatum, in order to explore their functional role in optimizing photosynthesis and in the control of reactive oxygen species (ROS) levels during the process. PMID- 27563304 TI - Epigenetic Control of Defense Signaling and Priming in Plants. AB - Immune recognition of pathogen-associated molecular patterns or effectors leads to defense activation at the pathogen challenged sites. This is followed by systemic defense activation at distant non-challenged sites, termed systemic acquired resistance (SAR). These inducible defenses are accompanied by extensive transcriptional reprogramming of defense-related genes. SAR is associated with priming, in which a subset of these genes is kept at a poised state to facilitate subsequent transcriptional regulation. Transgenerational inheritance of defense related priming in plants indicates the stability of such primed states. Recent studies have revealed the importance and dynamic engagement of epigenetic mechanisms, such as DNA methylation and histone modifications that are closely linked to chromatin reconfiguration, in plant adaptation to different biotic stresses. Herein we review current knowledge regarding the biological significance and underlying mechanisms of epigenetic control for immune responses in plants. We also argue for the importance of host transposable elements as critical regulators of interactions in the evolutionary "arms race" between plants and pathogens. PMID- 27563305 TI - Large-Scale Public Transcriptomic Data Mining Reveals a Tight Connection between the Transport of Nitrogen and Other Transport Processes in Arabidopsis. AB - Movement of nitrogen to the plant tissues where it is needed for growth is an important contribution to nitrogen use efficiency. However, we have very limited knowledge about the mechanisms of nitrogen transport. Loading of nitrogen into the xylem and/or phloem by transporter proteins is likely important, but there are several families of genes that encode transporters of nitrogenous molecules (collectively referred to as N transporters here), each comprised of many gene members. In this study, we leveraged publicly available microarray data of Arabidopsis to investigate the gene networks of N transporters to elucidate their possible biological roles. First, we showed that tissue-specificity of nitrogen (N) transporters was well reflected among the public microarray data. Then, we built coexpression networks of N transporters, which showed relationships between N transporters and particular aspects of plant metabolism, such as phenylpropanoid biosynthesis and carbohydrate metabolism. Furthermore, genes associated with several biological pathways were found to be tightly coexpressed with N transporters in different tissues. Our coexpression networks provide information at the systems-level that will serve as a resource for future investigation of nitrogen transport systems in plants, including candidate gene clusters that may work together in related biological roles. PMID- 27563306 TI - Evolution and Molecular Control of Hybrid Incompatibility in Plants. AB - Postzygotic reproductive isolation (RI) plays an important role in speciation. According to the stage at which it functions and the symptoms it displays, postzygotic RI can be called hybrid inviability, hybrid weakness or necrosis, hybrid sterility, or hybrid breakdown. In this review, we summarized new findings about hybrid incompatibilities in plants, most of which are from studies on Arabidopsis and rice. Recent progress suggests that hybrid incompatibility is a by-product of co-evolution either with "parasitic" selfish elements in the genome or with invasive microbes in the natural environment. We discuss the environmental influences on the expression of hybrid incompatibility and the possible effects of environment-dependent hybrid incompatibility on sympatric speciation. We also discuss the role of domestication on the evolution of hybrid incompatibilities. PMID- 27563307 TI - Anti-Trimeresurus albolabris venom IgY antibodies: preparation, purification and neutralization efficacy. AB - BACKGROUND: Snakebite incidence in southwestern China is mainly attributed to one of the several venomous snakes found in the country, the white-lipped green pit viper Trimeresurus albolabris. Since antivenom produced from horses may cause numerous clinical side effects, the present study was conducted aiming to develop an alternative antivenom antibody (immunoglobulin Y - IgY) from leghorn chickens. METHODS: IgY in egg yolk from white leghorn chicken previously injected with T. albolabris venom was extracted by water, precipitated by ammonium sulfate and purified by affinity chromatographic system. IgY was identified by SDS-PAGE, ELISA and Western blot, and its neutralizing assay was conducted on mice. RESULTS: Chickens injected multiple times with T. albolabris venom elicited strong antibody responses, and from their egg yolk IgY was isolated and purified, which exhibited a single protein band on SDS-PAGE and two bands (about 65 and 35 kDa, respectively) under reduced conditions. Immunoblot analysis revealed that these IgY are polyclonal antibodies since they bind with most venom components. In the neutralizing assay, all mice survived while the ratios of IgY/venom reached up to 3.79 (50.0 mg/13.2 mg). CONCLUSIONS: IgY antibody response was successfully conducted in white leghorn chicken injected with T. albolabris venom. IgY against T. albolabris venom was obtained for the first time, and it exhibited strong neutralizing potency on mice. These results may lay a foundation for the development of IgY antivenom with clinical applications in the future. PMID- 27563309 TI - The Adrenal Gland Volume Measurements in Manifestation of the Metabolic Status in Type-2 Diabetes Mellitus Patients. AB - Objectives. The aim of our study was to investigate the differences in adrenal gland volume between nondiabetic controls and Type-2 diabetic patients and to examine the influence of glycemic control in diabetes mellitus on adrenal gland volume. Methods. From March 2 to November 25, 2015, 62 consecutive patients with Type-2 DM along with 62 nondiabetics matched by age, gender, and BMI were enrolled in this prospective study. Our diabetes patients were categorized into two groups, well-controlled and poorly controlled diabetes groups. Adrenal volumetric measurements were performed by two radiologists, prospectively and independently, with semiautomatic software. Interobserver reliability was studied using the interobserver correlation coefficient (ICC). Results. The total adrenal volume (TAV) was significantly higher in Type-2 diabetic patients when compared with nondiabetic patients (p < 0.05). When we investigated diabetic patients according to glycemic controls, the TAVs in controlled diabetic patients were significantly higher than in those of the poorly controlled or uncontrolled diabetic patients (p < 0.05). Nondiabetic control patients have significantly smaller TAVs when compared to controlled and poorly or noncontrolled diabetic patients (p < 0.05). Conclusion. Our study suggests that adrenal gland volume measurement may be used as an indirect marker of glycemic control in patients with diabetes. PMID- 27563308 TI - PPAR Ligands Function as Suppressors That Target Biological Actions of HMGB1. AB - High mobility group box 1 (HMGB1), which has become one of the most intriguing molecules in inflammatory disorders and cancers and with which ligand-activated peroxisome proliferator-activated receptors (PPARs) are highly associated, is considered as a therapeutic target. Of particular interest is the fact that certain PPAR ligands have demonstrated their potent anti-inflammatory activities and potential anticancer effects. In this review article we summarize recent experimental evidence that PPAR ligands function as suppressors that target biological actions of HMGB1, including intracellular expression, receptor signaling cascades, and extracellular secretion of HMGB1 in cell lines and/or animal models. We also propose the possible mechanisms underlying PPAR involvement in inflammatory disorders and discuss the future therapeutic value of PPAR ligands targeting HMGB1 molecule for cancer prevention and treatment. PMID- 27563310 TI - Identification of Common Bacterial Pathogens Causing Meningitis in Culture Negative Cerebrospinal Fluid Samples Using Real-Time Polymerase Chain Reaction. AB - Background. Meningitis is a serious communicable disease with high morbidity and mortality rates. It is an endemic disease in Egypt caused mainly by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. In some settings, bacterial meningitis is documented depending mainly on positive cerebrospinal fluid (CSF) culture results or CSF positive latex agglutination test, missing the important role of prior antimicrobial intake which can yield negative culture and latex agglutination test results. This study aimed to utilize molecular technology in order to diagnose bacterial meningitis in culture-negative CSF samples. Materials and Methods. Forty culture-negative CSF samples from suspected cases of bacterial meningitis were examined by real-time polymerase chain reaction (real-time PCR) for the presence of lytA, bexA, and ctrA genes specific for Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, respectively. Results. Positive real-time PCR results for Streptococcus pneumoniae were detected in 36 (90%) of culture-negative CSF samples while no positive results for Haemophilus influenzae or Neisseria meningitidis were detected. Four (10%) samples were negative by real-time PCR for all tested organisms. Conclusion. The use of molecular techniques as real-time PCR can provide a valuable addition to the proportion of diagnosed cases of bacterial meningitis especially in settings with high rates of culture-negative results. PMID- 27563311 TI - Tympanometric Findings among Children with Adenoid Hypertrophy in Port Harcourt, Nigeria. AB - Introduction. Adenoid hypertrophy (AH) is a common childhood disorder. Adenoid plays a significant role in the pathogenesis of otitis media with effusion (OME). The aim of this study is to critically appraise the tympanometric finding among children with adenoid hypertrophy in Port Harcourt, Nigeria. Methodology. A Prospective, controlled study carried out among newly diagnosed cases of adenoid hypertrophy at the ENT clinic of the UPTH, between November 2014 and June 2015. Tympanometry was done on each child and each ear was considerably studied as a single entity. Types B and C tympanograms were used as indicators of OME. Data was collected and analyzed using SPSS version 20. Results. Sixty-eight cases of adenoid hypertrophy were seen within the study period and 136 ears were studied. Forty (29.4%) ears had type B tympanogram, while 36 (26.5%) ears had type C. The incidence of OME was 55.9%; there were 12 (17.6%) unilateral OME, while bilateral OME was 32 (47.1%). Grade 3 AH was prevalent and was statistically significant with the OME. Conclusion. This study had shown adenoidal hypertrophy as a significant risk factor for OME in children. There was more bilateral OME than unilateral. The more severe grade of AH was more prevalent and it was shown to be statistically significant with OME, thus being a significant risk factor for OME in children. This establishes the need for prompt hearing evaluation and management. PMID- 27563313 TI - Mesenchymal Transitions in Development and Disease. PMID- 27563312 TI - The Aryl Hydrocarbon Receptor Relays Metabolic Signals to Promote Cellular Regeneration. AB - While sensing the cell environment, the aryl hydrocarbon receptor (AHR) interacts with different pathways involved in cellular homeostasis. This review summarizes evidence suggesting that cellular regeneration in the context of aging and diseases can be modulated by AHR signaling on stem cells. New insights connect orphaned observations into AHR interactions with critical signaling pathways such as WNT to propose a role of this ligand-activated transcription factor in the modulation of cellular regeneration by altering pathways that nurture cellular expansion such as changes in the metabolic efficiency rather than by directly altering cell cycling, proliferation, or cell death. Targeting the AHR to promote regeneration might prove to be a useful strategy to avoid unbalanced disruptions of homeostasis that may promote disease and also provide biological rationale for potential regenerative medicine approaches. PMID- 27563314 TI - Clinical and Laboratory Findings That Differentiate Herpes Simplex Virus Central Nervous System Disease from Enteroviral Meningitis. AB - Background. It can be difficult for clinicians to distinguish between the relatively benign enteroviral (EnV) meningitis and potentially lethal herpes simplex virus (HSV) central nervous system (CNS) disease. Very limited evidence currently exists to guide them. Objective. This study sought to identify clinical features and cerebrospinal fluid (CSF) findings associated with HSV CNS disease. Methods. Given that PCR testing often is not immediately available, this chart review study sought to identify clinical and cerebrospinal fluid (CSF) findings associated with HSV meningitis over a 6-year period. In cases where PCR was not performed, HSV and EnV were assigned based on clinical criteria. Results. We enrolled 166 consecutive patients: 40 HSV and 126 EnV patients. HSV patients had a mean 40.4 versus 31.3 years for EnV, p = 0.005, seizures 21.1% versus 1.6% for EnV, p < 0.001, altered mental status 46.2% versus 3.2% for EnV, p < 0.001, or neurological deficits 44.7% versus 3.9% for EnV, p < 0.001. CSF neutrophils were lower in HSV (median 3.0% versus 9.5%, p = 0.0002); median lymphocytes (87.0% versus 67.0%, p = 0.0004) and protein (0.9 g/L versus 0.6 g/L, p = 0.0005) were elevated. Conclusion. Our study found that HSV patients were older and more likely to have seizure, altered mental status, or neurological deficits than patients with benign EnV meningitis. HSV cases had lower CSF neutrophils, higher lymphocytes, and higher protein levels. PMID- 27563315 TI - Investigating the effect of an empowerment program on physical activity of the elderly in Rezaeian Health Center, Iran, in 2014. AB - BACKGROUND: Reaching geriatric period is one of the greatest successes in human Beings. The older adults are predisposed to risk of many diseases and disabilities, and physical activity is one of the most efficient methods to prevent geriatric period disorders. Therefore, the present study aimed define the effect of an empowerment program on physical activity of the elderly residing in Shahid Rezaian health care center in 2014. MATERIALS AND METHODS: This quasi experimental study was conducted on 70 older adults, age 65 years and over, selected through convenient sampling and assigned to groups of study and control. Study group was divided into 5 seven-member subgroups and a one-hour session of physical exercises was administrated for them once a week for eight sequential weeks. All subjects evaluated before and after intervention by International Physical Activity Questionnaire. Subjects' physical activity was scored, based on the personal activity protocol,and the results were compared. Significance level was considered as P<0.05. RESULTS: Frequency distributions of the female subjects were 29 (82%) and 28 (80%) in study and control groups respectively. Mean (SD) scores of physical activity were 347.8 (174.1) and 321.7 (119.2) before intervention, and 641.3 (240.6) and 331.3 (101.5) after intervention in study and control groups respectively. Independent t-test showed a significant increase in physical activity score in study group, compared to control (t=4.06, P<0.001). CONCLUSIONS: The level of physical activity can be improved in the elderly through application of an empowerment program so as to take steps toward solving their immobility related problems and promoting their health through application of an empowerment program at this period of their life. PMID- 27563316 TI - Comparing the quality of life in insulin recipient and refusal patients with type 2 diabetes. AB - BACKGROUND: Better control of blood sugar and reduction of diabetes complications through insulin therapy could convince people to choose this method. However, patients might refuse insulin therapy due to its painful injection, limitations in daily activities, and hypoglycemia. Thus, insulin therapy could have both positive and negative effects on patients' quality of life (QOL). Therefore, the aim of this study was to compare the QOL of insulin recipient and insulin refusal patients with type 2 diabetes. MATERIALS AND METHODS: This study was a descriptive and comparative research conducted on 126 patients; 63 were insulin recipients and 63 had refused insulin therapy. Participants were under the care of the Endocrine and Metabolism Research Center of Isfahan, Iran. Data were gathered using the Diabetes Quality of Life (DQOL) questionnaire. In this tool, higher scores indicated lower QOL in patients. Data were analyzed using independent t-test, analysis of covariance, Mann-Whitney, Chi-square, and Pearson and Spearman's correlation. RESULTS: There was a significant difference (P < 0.001) between insulin recipient patients (mean = 2.02, SD = 0.31) and insulin refusal patients (mean = 1.74, SD = 0.41) in terms of mean QOL score. In addition, men and participants with higher educational levels reported a better QOL (P < 0.001). CONCLUSIONS: Results showed that insulin refusal patients had a better QOL. It seems that QOL is associated with the acceptance or refusal of insulin therapy. Therefore, enhancement of QOL could be related to all aspects of the disease, especially its treatment method and solving the therapeutic problems. PMID- 27563317 TI - The effect of mothers' empowerment program on premature infants' weight gain and duration of hospitalization. AB - BACKGROUND: The readiness of mothers to take care for infants at discharge is a critical issue. Poor readiness of mothers in taking care of premature infants at the time of discharge is associated with potential adverse consequences. This study examined the effect of implementing mothers' empowerment program on the weight gain and duration of hospitalization in premature infants. MATERIALS AND METHODS: This study was a quasi-experimental before-after study with a control group, in which 80 mothers with premature infants who were hospitalized in NICU Level II of two hospitals were recruited in the study. Mothers' empowerment program was implemented as a three-stage training program for the intervention group. Mothers' readiness questionnaire was completed by the mothers before the intervention and at the discharge time. The changes in mean of mothers' readiness scores were compared in both the groups. RESULTS: The mean of daily weight gain in infants of the intervention group (3.95 g) was significantly higher than that of the infants in the control group (-0.9 g) (P = 0.003). The average duration of hospitalization for infants in the intervention and control groups was 15.45 days and 20.95 days, respectively, showing a statistically significant difference (P = 0.003). CONCLUSIONS: Providing training to the mothers regarding how to care for premature infants can be a useful and effective method in the process of weight gain of premature and low-birth newborns, and may shorten the duration of infants' hospitalization. PMID- 27563318 TI - Evaluation of mint efficacy regarding dysmenorrhea in comparison with mefenamic acid: A double blinded randomized crossover study. AB - BACKGROUND: Menthol is the most important active material in mint and different mechanisms have been suggested for the way mint functions, most of which emphasize its analgesic effect owing to the presence of a group of temporary protein receptors. This study investigates the efficacy of peppermint capsule in the treatment of primary dysmenorrhea, in comparison with Mefenamic Acid and placebo. MATERIALS AND METHODS: This was a prospective, double-blinded, crossover study and was conducted on 127 girl students studying in Hamadan University of Medical Sciences who had experienced primary dysmenorrhea. Each participant was asked to take one of the drugs including Mefenamic Acid and Mint, starting from the first menstruation for 3 days. At the end of each period, a questionnaire was used to gather information; through the volunteer herself, pain intensity was recorded according to visual analog scale (VAS), duration of pain according to COX questionnaire, and bleeding amount according to pictorial blood loss assessment chart (PBAC) chart (Hygham). RESULTS: Average pain intensity and duration of pain were significantly lower after intake of Mefenamic Acid and Mint (P < 0.05). Average bleeding was significantly lower in those taking Mefenamic Acid capsule than in those taking peppermint extract (P < 0.05). Nausea and diarrhea were lower in the mint group than in Mefenamic Acid group. But analgesic usage was lower in Mefenamic Acid group than in peppermint group (P < 0.05). CONCLUSIONS: While the bleeding amount did not significantly change, pain and its severity and all the clinical signs and symptoms decreased after taking peppermint extract. Because the side effect of herbal drugs is lower than other medicinal drugs, using mint is advised for treating dysmenorrhea symptoms. PMID- 27563319 TI - Association between infertility factors and non-physical partner abuse in infertile couples. AB - BACKGROUND: Infertility predisposes the couples to mental and psychological problems such as anxiety, depression, anger, and partner abuse. This study aimed to investigate the association between infertility factors and the non-physical abuse between infertile spouses. MATERIALS AND METHODS: This is a descriptive cross-sectional study conducted on 262 infertile couples (131 female and 131 male), selected through convenient sampling, who referred to infertility centers in Isfahan. Data were collected by Partner Abuse Scale: Non-physical (PASNP), designed to measure the non-physical abuse experienced in relationship with partner and Non-physical Abuse of Partner Scale (NPAPS), designed to measure the non-physical abuse delivered upon the partner. All data were analyzed through SPSS version 16. RESULTS: Mean scores of NPAPS were 23.1% and 21.3% in men and women, respectively. Mean scores of PASNP were 13.8% and 20.3% among men and women, respectively. There was a significant difference in the mean scores of perceived non-physical partner abuse between men and women (P < 0.001). There was also a significant difference in the mean scores of perceived non-physical partner abuse and factor of infertility (P < 0.01). CONCLUSIONS: Perceived non physical abuse and delivered non-physical abuse upon the partner were low among infertile couples. Women had a higher perception of abuse when the cause of infertility was female factor, compared to men. However, special attention should be paid to infertile couples. Marital counseling, besides infertility counseling, should be conducted for these couples. PMID- 27563320 TI - Comparative study on the influence of three delivery positions on pain intensity during the second stage of labor. AB - BACKGROUND: Labor is a physiologic process, and consideration of labor pain and relieving that is among the major components of maternal care. Application of some labor position can lay the fetus better in pelvic canal direction. The present study aimed to investigate the effect of laying the mother in three labor positions on the pain severity in the second, third, and fourth stages of labor. MATERIALS AND METHODS: This is a clinical trial conducted on 96 primiparous pregnant women randomly selected through convenient sampling from those who were hospitalized in the hospitals of Isfahan and Jahrom. Women with a gestational age of 37-42 weeks, singleton pregnancy, who had passed the first labor stage through physiologic process, and with cephalic presentation were selected. The subjects were randomly allocated to be in the groups of lithotomy, sitting, and squatting positions. Pain severity in the second, third, and fourth labor stages was measured with visual analog scale (VAS) as well as McGill present pain intensity (PPI). The data were collected through interviews and observations with the help of VAS. The data were analyzed by Chi-square and Kruskal-Wallis statistical tests. RESULTS: In the latent phase of the second labor stage, mean pain severity in lithotomy (2.27) and squatting positions (2.48) was significantly less than the mean pain severity in sitting (5.33) position (P = 0.001). Pain severity in the active phase of the second and third labor stages was significantly less in squatting position (6.14) group compared to the other two groups (7.59 and 7.41 in sitting and lithotomy positions, respectively) (P = 0.024). Pain severity in the fourth labor stage showed no significant difference in all three groups. CONCLUSIONS: Application of various labor positions as one of the non medicational methods to reduce pain in the second and third stages of labor leads to labor pain reduction. PMID- 27563321 TI - Women's beliefs about infertility and sexual behaviors: A qualitative study. AB - BACKGROUND: Infertility is a reproductive health problem and its prevalence is increasing in developing countries. This problem has some significant effects on the sexual behaviors of infertile women, especially during infertility treatment periods. Discovering the existing beliefs in the field of sexual and reproductive health and also determining the misconceptions would define the educational needs for providing sexual health programs for infertile women. Women should be able to distinguish risky behaviors from healthy behaviors that falsely have been marked as infertility-related behaviors. This qualitative study was conducted to determine women's beliefs about infertility and sexual behaviors among Iranian infertile women. MATERIALS AND METHODS: The present study was a qualitative conventional content analysis study conducted on 15 infertile women and 8 key informants until reaching data saturation. Guba and Lincoln evaluative criteria were used for ensuring rigor of the study. RESULTS: Data analysis defined three classes of beliefs that directly or indirectly affected sexual behaviors in infertile women: 1) Cultural, religious, or ethnic beliefs, 2) believing in the effect of diet on infertility, and 3) effect of the type of intercourse on getting pregnant. CONCLUSIONS: Three themes of religious, cultural, and ethnic beliefs, believing in the effect of diet on infertility, and the effect of the type of intercourse were the most important factors indicating sexual behaviors among infertile women. It seems that cultural and social matters are the most effective factors on sexual behaviors of infertile Iranian women. PMID- 27563322 TI - Relationship between fatigue and sleepiness with general health of mothers in the postpartum period. AB - BACKGROUND: Fatigue and changes in sleep patterns are one of the impressive features in the first year after birth, which have negative effects on work, family life, and social relationships. Therefore, the objective of this research was to investigate the relationship between fatigue and Stanford sleepiness with the general health of mothers in the postpartum period. MATERIALS AND METHODS: The current research is a descriptive correlational study which was performed on 190 mothers between 2 and 24 postpartum weeks, referring to the health centers of Isfahan in 2014. All mothers meeting the inclusion criteria were selected through cluster purposive sampling. Data were collected by use of four questionnaires including profile and fertility, fatigue, Stanford sleepiness, and general health. Data were analyzed by statistical tests at a significance level of <=0.05. RESULTS: The results showed that 5.3%, 59.5%, and 35.3% of subjects had mild, moderate, and severe fatigue, respectively. In addition, 26.3% of women showed a public health disorder, and according to Stanford sleepiness, 20.5% of subjects had sleepiness. The statistical results indicated that there were significant relationships between fatigue (P <= 0.001, r = 0.52) and Stanford sleepiness (P = 0.04, r = 0.14), and mothers' general health. CONCLUSIONS: According to prevalence of fatigue and sleepiness in the postpartum period and its relationship with maternal health, application of sleep health education and appropriate counseling during pregnancy and after delivery is recommended to prevent mothers' mental complications in order to achieve a safe pregnancy. PMID- 27563323 TI - Effects of music therapy on pain responses induced by blood sampling in premature infants: A randomized cross-over trial. AB - BACKGROUND: Premature infants are subjected to many painful procedures during care and treatment. The aim of this study was to assess the effect of music therapy on physiological and behavioral pain responses of premature infants during and after blood sampling. MATERIALS AND METHODS: This study was a cross over clinical trial conducted on 20 infants in a hospital affiliated to Tehran University of Medical Sciences for a 5-month period in 2011. In the experimental group, Transitions music was played from 5 min before until 10 min after blood sampling. The infants' facial expressions and physiological measures were recorded from 10 min before until 10 min after sampling. All steps and measurements, except music therapy, were the same for the control group. Data were analyzed using SAS and SPSS software through analysis of variance (ANOVA) and Chi-square tests. RESULTS: There were significant differences between the experimental and control groups (P = 0.022) in terms of heart rate during needle extraction and at the first 5 min after sampling (P = 0.005). Considering the infant's sleep-wake state in the second 5 min before sampling, the statistical difference was significant (P = 0.044). Difference was significant (P = 0.045) during injection of the needle, in the first 5 min after sampling (P = 0.002), and in the second 5 min after sampling (P = 0.005). There were significant difference in infants' facial expressions of pain in the first 5 min after sampling (P = 0.001). CONCLUSIONS: Music therapy reduces the physiological and behavioral responses of pain during and after blood sampling. PMID- 27563324 TI - Effect of lavender essence inhalation on the level of anxiety and blood cortisol in candidates for open-heart surgery. AB - BACKGROUND: Surgery, as a treatment, is a stressful experience. The anxiety is more severe in open-heart surgery patients due to its risk and complications. The present study aimed to determine the effect of lavender essence on the levels of anxiety and blood cortisol in candidates for open-heart surgery. MATERIALS AND METHODS: This was a single-blind clinical trial, a random allocation study with a control group conducted on 90 candidates for open-heart surgery in two groups of study and control. The study and control groups inhaled two drops of lavender and distilled water for 20 min, respectively. Spielberger questionnaire was filled by the patients. A 2 ml blood sample was taken to measure the cortisol level and patients' vital signs were recorded before and after intervention. Data were analyzed by chi-square in the form of mean, SD, and frequency distribution, independent t-test, paired t-test, and analysis of covariance (ANCOVA), with a significance level of P = 0.05 to modify the pre-test scores. RESULTS: Results showed a significant reduction in mean anxiety score from 56.73 (5.67) to 54.73 (5.42) after intervention in the study group, compared to the control group [1.11 (1.17)] (P < 0.001). There was also a higher difference in cortisol level in the study group compared to the control group [1.88 (0.56) vs. 0.42 (0.45)]. ANCOVA test showed that the 10.8% variance in anxiety score and 69.6% decrease in blood cortisol resulted from inhalation of lavender. CONCLUSIONS: Results showed the positive effect of lavender essence on anxiety and blood cortisol level among the patients. Aromatherapy with lavender is suggested to be considered as a nursing intervention in clinical settings. PMID- 27563325 TI - Comparing the effects of two Swedish massage techniques on the vital signs and anxiety of healthy women. AB - BACKGROUND: Anxiety is an inseparable part of our lives and a serious threat to health. Therefore, it is necessary to use certain strategies to prevent disorders caused by anxiety and adjust the vital signs of people. Swedish massage is one of the most recognized techniques for reducing anxiety. This study aims to compare the effects of two massage techniques on the vital signs and anxiety of healthy women. MATERIALS AND METHODS: This quasi-experimental study with a two-group, crossover design was conducted on 20 healthy women who were selected by simple sampling method and were randomly assigned to BNC (Back, Neck, and Chest) or LAF (Leg, Arm, and Face) groups. Massage therapy was carried out for a 14-week period (two 4-week massage therapy sessions and 6 weeks washout stage). Gathered data were analyzed using paired t-test with a significance level of P < 0.05. RESULTS: Both BNC and LAF methods caused a significant decrease in systolic BP in the first stage (P = 0.02, 0.00); however, diastolic BP showed significant decrease only in BNC group (P = 0.01). The mean average of body temperature of LAF group showed a significant decrease in the first stage (P = 0.0.3), and pulse and respiratory rate showed significant decrease in both groups during the second stage (P = 0.00). In addition, anxiety scores showed no significant difference before and after massage therapy (P < 0.05). CONCLUSIONS: Massage therapy caused a decrease in systolic BP, pulse, and respiratory rate. It can be concluded that massage therapy was useful for decreasing the vital signs associated with anxiety in healthy women. PMID- 27563326 TI - The main concern of burn survivors in Iran. AB - BACKGROUND: The present work was conducted to study the burn patients' experiences to get an insight into their main concerns when they suffer the tragic event, recover from it, and adjust back in the society, so that better rehabilitation programs can be planned corresponding to their needs as well as to the needs of the society and the existing situations. MATERIALS AND METHODS: In this qualitative study, 17 burn survivors were enrolled. Unstructured interviews were used for data collection. All the interviews were recorded, transcribed, and analyzed using qualitative content analysis method. RESULTS: Based on the existing elements of the explicit textual meanings, two categories of threat and disturbance were formed. The category of threat was extracted from the following five subcategories: (a) Threat to physical life; (b) threat to the process of living; (c) psychological threat; (d) spiritual threat; and (e) social threat. The category of disturbance was extracted from the following three subcategories: (a) Sensory disturbance: Suffering pain; (b) self-concept disturbance; and (c) behavioral disturbance. CONCLUSIONS: Burn survivors experience severe pain, enduring and suffering in their daily activities after burn. Passing through these difficult trajectories is perceived as a threat and disturbance in self integrity. PMID- 27563327 TI - Cross-cultural adaptation and validation of the Persian version of the Intermittent and Constant Osteoarthritis Pain Measure for the knee. AB - OBJECTIVE: The present study aimed to translate and evaluate the reliability and validity of the Persian version of the 11-item Intermittent and Constant Osteoarthritis Pain (ICOAP) measure in Iranian subjects with Knee Osteoarthritis (KOA). MATERIALS AND METHODS: The ICOAP questionnaire was translated according to the Manufacturers Alliance for Productivity and Innovation (MAPI) protocol. The procedure consisted of forward and backward translation, as well as the assessment of the psychometric properties of the Persian version of the questionnaire. A sample of 230 subjects with KOA was asked to complete the Persian versions of ICOAP and Knee injury and Osteoarthritis Outcome Score (KOOS). The ICOAP was readministered to forty subjects five days after the first visit. Test-retest reliability was assessed using Intraclass Correlation Coefficient (ICC), and internal consistency was assessed by Cronbach's alpha and item-total correlation. The correlation between ICOAP and KOOS was determined using Spearman's correlation coefficient. RESULT: Subjects found the Persian version of the ICOAP to be clear, simple, and unambiguous, confirming its face validity. Spearman correlations between ICOAP total and subscale scores with KOOS scores were between 0.5 and 0.7, confirming construct validity. Cronbach's alpha, used to assess internal consistency, was 0.89, 0.93, and 0.92 for constant pain, intermittent pain, and total pain scores, respectively. The ICC was 0.90 for constant pain and 0.91 for the intermittent pain and total pain score. CONCLUSION: The Persian version of the ICOAP is a reliable and valid outcome measure that can be used in Iranian subjects with KOA. PMID- 27563328 TI - The relationship between nurses' clinical competence and burnout in neonatal intensive care units. AB - BACKGROUND: Nurses' clinical competency plays an important role in the care of preterm infants. On the other hand, burnout is one of the most important factors in reducing the nurses' efficiency. With regard to the importance of the role of nurses, and the vulnerability of the infants, the purpose of this study was to investigate the relationship between nurses' burnout and clinical competency in NICUs. MATERIALS AND METHODS: The descriptive cross-sectional study was conducted with the participation of 86 nurses working in the NICUs of hospitals in Isfahan, Iran. Census sampling method was used in the NICUs of educational hospitals in 2014. Data were collected by a questionnaire including demographic characteristics, Patricia clinical competency, and Maslach burnout scales. Data were analyzed by the statistical tests of independent t-test and Pearson correlations test with the significance level of alpha < 0.05. RESULTS: Six dimensions of clinical competency and three dimensions of nurses' burnout were assessed at three levels (weak, moderate, and strong levels). Statistical tests showed that clinical competency was at a moderate level in all fields. Of the dimensions of nurses' burnout, emotional exhaustion was moderate, depersonalization was weak, and personal performance was strong. The results showed that nurses' burnout and clinical competency in the NICUs were at a moderate level and had a significant negative relationship (r = -0.322, P = 0.003). CONCLUSIONS: Results showed that burnout had a negative relationship with competency. Therefore, managers are suggested to improve nurses' competency and diminish their job burnout through better and more applicable planning. PMID- 27563329 TI - Investigating the effect of education based on need to prevent falling during activities of daily living among the elderlies referring to health centers of Isfahan. AB - BACKGROUND: Falling has a great importance among the elderlies. Even if no physical injury occurs, it can cause fear of falling down again and, consequently, reduce older adults' activities. With regard to the prevalence of falling among older adults, its prevention is essential. Therefore, the present study was aimed to define the effect of need-based education on prevention of older adults' falling during their everyday life activities. MATERIALS AND METHODS: This is a quasi-experimental study. Study population comprised all the older adults of age 60 years and over referring to health care centers in Isfahan. Through multiple random sampling, 15 older adults were selected from four health care centers. Data collection tool in the present study was Daily Activity Questionnaire. RESULTS: Results showed a significant difference between the mean of daily activity scores in the intervention group before, immediately after, and 1 month after the intervention (12, 13.6, and 13.5, respectively; P = 0.01). Meanwhile, there was no significant deference between the scores immediately after and 1 month after the intervention. There was no significant difference observed between the three time points in the control group (mean = 12.3; P = 0.907). CONCLUSION: Implementation of education concerning prevention of older adults' falling led to improvement of their daily activity in the intervention group. PMID- 27563330 TI - The effect of teacher's presence at children's bedside on the anxiety of mothers with hospitalized children: A randomized clinical trial. AB - BACKGROUND: The hospitalization of a child is a stressful experience for parents, especially mothers. Not having access to the teacher and not being able to continue school studies within the hospital by hospitalized children is a common reason for anxiety in them and their parents. The current study aimed to determine the effect of teacher's presence at children's bedside on the anxiety of mothers with hospitalized children. MATERIALS AND METHODS: In a randomized clinical trial, a total of 50 mothers with children admitted to pediatric ward of one teaching hospital in Mashhad, Iran, were randomly allocated to two equal groups. In the intervention group, the teacher was present at children's bedside for daily education and practices, but the control group received standard routine care. The mothers' level of anxiety was evaluated using the Spielberger State-Trait Anxiety Inventory, which was completed at both admission and prior to child's discharge. Data were analyzed using SPSS. RESULTS: The results showed that before intervention, the means and standard deviations of the mothers' trait anxiety scores in the experimental and control groups were not significantly different (P = 0.164). However, after intervention, the mothers' mean trait anxiety scores decreased significantly in the intervention group compared to the control group (P < 0.001) and compared to the pre-intervention phase (P < 0.001). CONCLUSIONS: It seems that the presence of a teacher at children's bedside is an easy and effective strategy to reduce anxiety in mothers regarding their children hospitalization. PMID- 27563331 TI - Investigation of the relationship between personality characteristics and vasomotor symptoms in menopausal women. AB - BACKGROUND: Research demonstrates that most of the menopausal symptoms and problems are the reflection of individual and social circumstances rather than the endocrine events of the menopause. As majority of women live 30 years or more through postmenopausal period, treatment and following up their problems during this period is among the main duties of a midwife. The aim of this study is to determine the relationship between personality traits and vasomotor symptoms in postmenopausal women. MATERIALS AND METHODS: This correlation study was conducted on 400 postmenopausal women referring to the training maternity centers of Mashhad, Iran. Subjects were selected through simple sampling method and filled NEO Five-Factor Inventory (NEO-FFI (questionnaire. Their daily records of hot flashes and night sweats were also collected. NEO-FFI questionnaire assesses the five personality aspects of neuroticism, extraversion, openness to experience, conscientiousness, and agreeableness. After the data were collected, they were analyzed by Pearson and Spearman correlation coefficients, Mann-Whitney, Kruskal Wallis, and linear regression statistical tests. P < 0.05 was considered as a statistically significant value. RESULTS: Most of the women were in average level of personality traits. Among the aspects of personality traits, there was a significant correlation between intensity of hot flashes (P = 0.041) and night sweats (P = 0.028), and conscientiousness. CONCLUSIONS: According to the results of the study, during treatment of the vasomotor symptoms, a midwife should pay close attention to the personality of postmenopausal women to achieve an effective treatment. These women should also be referred to a psychologist, if needed. PMID- 27563332 TI - Ligustrazine Inhibits Cartilage Endplate Hypertrophy via Suppression of TGF beta1. AB - CEP hypertrophy is one of the characteristics of intervertebral disc degeneration (IDD). LIG exerts a protective effect on IDD in animal model. The effect of LIG on CEP hypertrophy is further investigated in the present study. Cells were isolated from hypertrophic samples obtained from patients during vertebral fusion surgery. Cellular proliferation and the expression of type I collagen (Col I) and TGF-beta1 were tested. In the bipedal rats, the edges of the CEP and the sizes of noncartilaginous outgrowth, as well as the expression of osteogenic markers, Col1a, ALP, Runx2, and TGF-beta1, were detected. Within two passages, the condensed hypertrophic CEP cells exhibited osteogenic capacity by bony-like nodules and ALP positive staining, along with increased expression of Col I and TGF-beta1. LIG inhibited proliferation of CEP cells and downregulated the expression of Col I and TGF-beta1 in vitro. Furthermore, LIG attenuated CEP hypertrophy on the lumbar spine of bipedal rats by reducing Col1a, ALP, Runx2, and TGF-beta1 mRNA expression and TGF-beta1 distribution in vivo. We concluded LIG exerted a preventive effect on CEP hypertrophy via suppression of TGF-beta1 levels. This information could be used to develop alternative therapeutic methods to treat spinal CEP hypertrophy. PMID- 27563333 TI - Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats. AB - Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1beta, IL-6, and IL-10, and tumor necrosis factor- (TNF-) alpha expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14-18 days. All biomarkers were improved in treated groups with shorter recovery times of 4-10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID- 27563334 TI - Anti-Inflammatory Activity of Bee Venom in BV2 Microglial Cells: Mediation of MyD88-Dependent NF-kappaB Signaling Pathway. AB - Bee venom has long been used as a traditional folk medicine in Korea. It has been reportedly used for the treatment of arthritis, cancer, and inflammation. Although its anti-inflammatory activity in lipopolysaccharide- (LPS-) stimulated inflammatory cells has been reported, the exact mechanism of its anti inflammatory action has not been fully elucidated. Therefore, the aim of this study was to investigate the anti-inflammatory mechanism of bee venom in BV2 microglial cells. We first investigated whether NO production in LPS-activated BV2 cells was inhibited by bee venom, and further iNOS mRNA and protein expressions were determined. The mRNA and protein levels of proinflammatory cytokines were examined using semiquantitative RT-PCR and immunoblotting, respectively. Moreover, modulation of the transcription factor NF-kappaB by bee venom was also investigated using a luciferase assay. LPS-induced NO production in BV2 microglial cells was significantly inhibited in a concentration-dependent manner upon pretreatment with bee venom. Bee venom markedly reduced the mRNA expression of COX-2, TNF-alpha, IL-1beta, and IL-6 and suppressed LPS-induced activation of MyD88 and IRAK1 and phosphorylation of TAK1. Moreover, NF-kappaB translocation by IKKalpha/beta phosphorylation and subsequent IkappaB-alpha degradation were also attenuated. Thus, collectively, these results indicate that bee venom exerts its anti-inflammatory activity via the IRAK1/TAK1/NF-kappaB signaling pathway. PMID- 27563335 TI - Phytochemical Profile and Antibacterial and Antioxidant Activities of Medicinal Plants Used by Aboriginal People of New South Wales, Australia. AB - Aboriginal people of Australia possess a rich knowledge on the use of medicinal plants for the treatment of sores, wounds, and skin infections, ailments which impose a high global disease burden and require effective treatments. The antibacterial and antioxidant activities and phytochemical contents of extracts, obtained from eight medicinal plants used by Aboriginal people of New South Wales, Australia, for the treatment of skin related ailments, were assessed to add value to and provide an evidence-base for their traditional uses. Extracts of Acacia implexa, Acacia falcata, Cassytha glabella, Eucalyptus haemastoma, Smilax glyciphylla, Sterculia quadrifida, and Syncarpia glomulifera were evaluated. All extracts except that of S. quadrifida showed activity against sensitive and multidrug resistant strains of Staphylococcus aureus with minimum inhibitory concentration values ranging from 7.81 to 1000 MUg/mL. The sap of E. haemastoma and bark of A. implexa possessed high total phenolic contents (TPC) and strong DPPH radical scavenging abilities. A positive correlation was observed between TPC and free radical scavenging ability. GC-MS analysis of the n-hexane extract of S. glomulifera identified known antimicrobial compounds. Together, these results support the traditional uses of the examined plants for the treatment of skin related ailments and infections by Aboriginal people of New South Wales, Australia. PMID- 27563336 TI - Influence of Temperature on Free Radical Generation in Propolis-Containing Ointments. AB - Free radicals thermally generated in the ointments containing propolis were studied by electron paramagnetic resonance (EPR) spectroscopy. The influence of temperature on the free radical concentration in the propolis ointments was examined. Two ointment samples with different contents of propolis (5 and 7%, resp.) heated at temperatures of 30 degrees C, 40 degrees C, 50 degrees C, and 60 degrees C, for 30 min., were tested. Homogeneously broadened EPR lines and fast spin-lattice interactions characterized all the tested samples. Free radicals concentrations in the propolis samples ranged from 10(18) to 10(20) spin/g and were found to grow in both propolis-containing ointments along with the increasing heating temperature. Free radical concentrations in the ointments containing 5% and 7% of propolis, respectively, heated at temperatures of 30 degrees C, 40 degrees C, and 50 degrees C were only slightly different. Thermal treatment at the temperature of 60 degrees C resulted in a considerably higher free radical formation in the sample containing 7% of propolis when related to the sample with 5% of that compound. The EPR examination indicated that the propolis ointments should not be stored at temperatures of 40 degrees C, 50 degrees C, and 60 degrees C. Low free radical formation at the lowest tested temperatures pointed out that both examined propolis ointments may be safely stored up to the temperature of 30 degrees C. PMID- 27563338 TI - CytoJournal Quiz Cases: Publishing open-access, PubMed-searchable cytopathology cases with educational messages. PMID- 27563339 TI - Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor. AB - Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42 year-old female had a history of bilateral SBT and postbilateral salpingo oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis. PMID- 27563337 TI - The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress. AB - ER stress has been implicated in pathophysiological development of many diseases. Persistent overwhelming stimuli trigger ER stress to initiate apoptosis, autophagy, and cell death. IRE1-JNK and eIF2alpha-CHOP signaling pathways are the two important players of ER stress, which is also modulated by ROS production, calcium disturbance, and inflammatory factors. ER stress has been developed as a novel strategy for diseases management. Recently, a vast of research focuses on the natural occurring compounds targeting ER stress, which results in medical benefits to human diseases. These small reported molecules mainly include polyphenols, alkaloids, and saponins. Many of them have been developed for use in clinical applications. To better understand the pharmacological mechanism of these molecules in ER stress in diseases, efforts have been made to discover and deliver medical merits. In this paper, we will summarize the natural occurring compounds targeting ER stress. PMID- 27563340 TI - Tuberculous lymphadenitis: Comparison of cytomorphology, Ziehl-Neelsen staining, and rapid mycobacterial culture at a pediatric superspecialty hospital. AB - BACKGROUND: To evaluate and compare the role of Ziehl-Neelsen (ZN) staining and mycobacterial culture in diagnosis of tuberculous lymphadenitis. MATERIALS AND METHODS: A total of 56 fine needle aspirations (FNAs) from patients who were clinically suspected to have tuberculous lymphadenitis were included. Acid-fast Bacilli detection was attempted by ZN staining on smears as well as culture on Middlebrook 7H9 broth. Percentage positivity of both smears and culture was calculated. RESULTS: Of the 56 cases, 46 showed cytomorphological features consistent with tuberculosis (TB). The most common pattern was only necrosis in 37 cases followed by necrotizing granulomas in 13 cases. ZN-stained smears were positive in 40 cases while culture was positive in only 27 cases. The highest smear and culture positivity was noted in cases with only necrosis. In six cases, diagnosis of TB was made on culture alone since smear was negative in these cases. CONCLUSION: FNA is a reliable technique for early and accurate diagnosis of tuberculous lymphadenitis in many cases. Mycobacterial culture by newer rapid techniques can assist in bacillary detection in smear-negative cases and also allows for drug sensitivity testing. Hence, culture should be resorted to in such cases. PMID- 27563341 TI - Resolving the evolution of the mammalian middle ear using Bayesian inference. AB - BACKGROUND: The minute, finely-tuned ear ossicles of mammals arose through a spectacular evolutionary transformation from their origins as a load-bearing jaw joint. This involved detachment from the postdentary trough of the mandible, and final separation from the dentary through resorption of Meckel's cartilage. Recent parsimony analyses of modern and fossil mammals imply up to seven independent postdentary trough losses or even reversals, which is unexpected given the complexity of these transformations. Here we employ the first model based, probabilistic analysis of the evolution of the definitive mammalian middle ear, supported by virtual 3D erosion simulations to assess for potential fossil preservation artifacts. RESULTS: Our results support a simple, biologically plausible scenario without reversals. The middle ear bones detach from the postdentary trough only twice among mammals, once each in the ancestors of therians and monotremes. Disappearance of Meckel's cartilage occurred independently in numerous lineages from the Late Jurassic to the Late Cretaceous. This final separation is recapitulated during early development of extant mammals, while the earlier-occurring disappearance of a postdentary trough is not. CONCLUSIONS: Our results therefore suggest a developmentally congruent and directional two-step scenario, in which the parallel uncoupling of the auditory and feeding systems in northern and southern hemisphere mammals underpinned further specialization in both lineages. Until ~168 Ma, all known mammals retained attached middle ear bones, yet all groups that diversified from ~163 Ma onwards had lost the postdentary trough, emphasizing the adaptive significance of this transformation. PMID- 27563342 TI - Recent Advances in Statistical Data and Signal Analysis: Application to Real World Diagnostics from Medical and Biological Signals. PMID- 27563343 TI - IASM: A System for the Intelligent Active Surveillance of Malaria. AB - Malaria, a life-threatening infectious disease, spreads rapidly via parasites. Malaria prevention is more effective and efficient than treatment. However, the existing surveillance systems used to prevent malaria are inadequate, especially in areas with limited or no access to medical resources. In this paper, in order to monitor the spreading of malaria, we develop an intelligent surveillance system based on our existing algorithms. First, a visualization function and active surveillance were implemented in order to predict and categorize areas at high risk of infection. Next, socioeconomic and climatological characteristics were applied to the proposed prediction model. Then, the redundancy of the socioeconomic attribute values was reduced using the stepwise regression method to improve the accuracy of the proposed prediction model. The experimental results indicated that the proposed IASM predicted malaria outbreaks more close to the real data and with fewer variables than other models. Furthermore, the proposed model effectively identified areas at high risk of infection. PMID- 27563344 TI - The Hybrid Feature Selection Algorithm Based on Maximum Minimum Backward Selection Search Strategy for Liver Tissue Pathological Image Classification. AB - We propose a novel feature selection algorithm for liver tissue pathological image classification. To improve the efficiency of feature selection, the same feature values of positive and negative samples are removed in rough selection. To obtain the optimal feature subset, a new heuristic search algorithm, which is called Maximum Minimum Backward Selection (MMBS), is proposed in precise selection. MMBS search strategy has the following advantages. (1) For the deficiency of Discernibility of Feature Subsets (DFS) evaluation criteria, which makes the class of small samples invalid for unbalanced samples, the Weighted Discernibility of Feature Subsets (WDFS) evaluation criteria are proposed as the evaluation strategy of MMBS, which is also available for unbalanced samples. (2) For the deficiency of Sequential Forward Selection (SFS) and Sequential Backward Selection (SBS), which can only add or only delete feature, MMBS decides whether to add the feature to feature subset according to WDFS criteria for each feature firstly; then it decides whether to remove the feature from feature subset according to SBS algorithm. In this way, the better feature subset can be obtained. The experiment results show that the proposed hybrid feature selection algorithm has good classification performance for liver tissue pathological image. PMID- 27563345 TI - The International College of Psychosomatic Medicine - a personal history. AB - This is a history of the International College of Psychosomatic Medicine from 1970 to the present. PMID- 27563346 TI - Laparoscopic radical prostatectomy outcome data: how should surgeon's performance be reported? A retrospective learning curve analysis of two surgeons. AB - OBJECTIVE: To document the learning curve for the laparoscopic radical prostatectomy (LRP) procedure and discuss the optimal usage of prospectively documented outcome data for reporting a surgeon's performance. MATERIALS AND METHODS: Using prospectively collected data from the first series of patients to undergo LRP by two surgeons in the same institution, linear and logistic regression multivariate analyses per 25 patients were carried out to graphically represent the surgical learning curve for operative time, blood loss, complications, length of stay (LOS), and positive margins. Surgeon A carried out 275 operations between 2003-2009; Surgeon B carried out 225 between 2008-2012. RESULTS: Learning curves showing continuous improvement of each of the above outcomes were demonstrated for both cohorts. For surgeon A, a plateau was observed for LOS and T2 positive margins after 100 and 150 surgeries respectively. No such plateau was observed for surgeon B. CONCLUSION: On documenting these learning curves and discussion of the reporting methods used, we concluded that the most informative outcome measure, with the least potential observer bias was T2 positive margins. Whether as a single measure or in combination with others, this has potential for use as an objective outcome representative of improvement in a surgeon's skill over time. PMID- 27563347 TI - Best practices in developing a national palliative care policy in resource limited settings: lessons from five African countries. AB - Given the high unmet need for palliative care in Africa and other resource limited settings, it is important that countries embrace the public health approach to increasing access through its integration within existing healthcare systems. To give this approach a strong foundation that would ensure sustainability, the World Health Organisation urges member states to ensure that policy environments are suitable for this intervention. The development, strengthening, and implementation of national palliative care policies is a priority. Given the lack of a critical mass of palliative care professionals in the region and deficiency in documenting and sharing best practices as part of information critical for regional development, policy development becomes a complex process. This article shares experiences with regard to best practices when advocating the national palliative care policies. It also tells about policy development process, the important considerations, and cites examples of policy content outlines in Africa. PMID- 27563348 TI - Interventions geared towards strengthening the health system of Namibia through the integration of palliative care. AB - The high burden of non-communicable diseases and communicable diseases in Africa characterised by late presentation and diagnosis makes the need for palliative care a priority from the point of diagnosis to death and through bereavement. Palliative care is an intervention that requires a multidisciplinary team to address the multifaceted needs of the patient and family. Thus, its development takes a broad approach that involves engaging all key stakeholders ranging from policy makers, care providers, educators, the public, patients, and families. The main focus of stakeholder engagement should address some core interventions geared towards improving knowledge and awareness, strengthening skills and attitudes about palliative care. These interventions include educating health and allied healthcare professionals on the palliative care-related problems of patients and best practices for care, explaining palliative care as a clinical and holistic discipline and demonstrating its effectiveness, the need to include palliative care into national policies, strategic plans, training curriculums of healthcare professionals and the engagement of patients, families, and communities. Interventions from a five-year programme that was aimed at strengthening the health system of Namibia through the integration of palliative care for people living with HIV and AIDS and cancer in Namibia are shared. This article illustrates how a country can implement the World Health Organisation's public health strategy for developing palliative care services, which recommends four pillars: government policy, education, drug availability, and implementation. PMID- 27563349 TI - The Island Hospice model of palliative care. AB - There has been a substantial increase in cancer detections in Africa over years, and it has also been noted that higher number of individuals are affected by the later stages of cancer that lead to death. When it comes to cancer care, Zimbabwe is no exception with its ongoing palliative care related research, though still in its infancy. The need for advanced and more accessible palliative care to assist the vulnerable has been intensified by this increase in cancer prevalence. Island Hospice, which is a centre of excellence in palliative care has varying elements of the models that it employs to engage those most in need of palliative assistance, especially children and financially-challenged individuals. PMID- 27563350 TI - Kenya Hospices and Palliative Care Association: integrating palliative care in public hospitals in Kenya. AB - BACKGROUND: In Kenya, cancers as a disease group rank third as a cause of death after infectious and cardiovascular diseases. It is estimated that the annual incidence of cancer is about 37,000 new cases with an annual mortality of 28,000 cases (Kenya National Cancer Control Strategy 2010). The incidence of non communicable diseases accounts for more than 50% of total hospital admissions and over 55% of hospital deaths (Kenya National Strategy for the Prevention and Control of Non Communicable Diseases 2015-2020). The prevalence of HIV is 6.8 (KIAS 2014). Most of these patients will benefit from palliative care services, hence the need to integrate palliative care services in the public healthcare system. METHOD: The process of integrating palliative care in public hospitals involved advocacy both at the national level and at the institutional level, training of healthcare professionals, and setting up services within the hospitals that we worked with. Technical support was provided to each individual institution as needed. RESULTS: Eleven provincial hospitals across the country have now integrated palliative care services (Palliative Care Units) and are now centres of excellence. Over 220 healthcare providers have been trained, and approximately, over 30,000 patients have benefited from these services. Oral morphine is now available in the hospital palliative care units. CONCLUSION: As a success of the pilot project, Kenya Hospices and Palliative Care Association (KEHPCA) is now working with the Ministry of Health Kenya to integrate palliative care services in 30 other county hospitals across the country, thus ensuring more availability and access to more patients. Other developing countries can learn from Kenya's successful experience. PMID- 27563351 TI - Integration of legal aspects and human rights approach in palliative care delivery-the Nyeri Hospice model. AB - Palliative care is patient and family-centred care that optimises quality of life by anticipating, preventing, and treating suffering. Open Society Foundation public health program (2011) notes that people facing life-threatening illnesses are deeply vulnerable: often in severe physical pain, worried about death, incapacitation, or the fate of their loved ones. Legal issues can increase stress for patients and families and make coping harder, impacting on the quality of care. In the absence of a clear legal provision expressly recognising palliative care in Kenya, providers may face numerous legal and ethical dilemmas that affect the availability, accessibility, and delivery of palliative care services and commodities. In order to ensure positive outcomes from patients, their families, and providers, palliative care services should be prioritised by all and includes advocating for the integration of legal support into those services. Palliative care service providers should be able to identify the various needs of patients and their families including specific issues requiring legal advice and interventions. Access to legal services remains a big challenge in Kenya, with limited availability of specialised legal services for health-related legal issues. An increased awareness of the benefits of legal services in palliative care will drive demand for easily accessible and more affordable direct legal services to address legal issues for a more holistic approach to quality palliative care. PMID- 27563352 TI - Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience. AB - The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy. PMID- 27563353 TI - Highlights from the first International ecancer Conference on Oncology and Radiotherapy, 6-7 May 2016, Santiago, Chile. AB - The first international ecancer conference on oncology and radiotherapy was held in Santiago de Chile on 6 and 7 May 2016. It was chaired by Dr Beatriz Amendola, Professor Gordon McVie and Professor Umberto Veronesi. Specialists from Europe and America were invited as guest lecturers. Over 300 people are attended the conference from all areas of oncology, doctors, physicists, medical technologists, nurses, residents, students, social workers, journalists, pharmaceutical chemists, from all over the country and abroad, including India. The success was achieved as a result of the multidisciplinary approach to the pathologies, which prompted significant interest from the audience. The 'eContouring' course (radio-oncologists) was taken by a large number of participants, the result of great interest in the subject, and the undoubtable merit of the guest instructors. For the opening ceremony, we were honoured with the presence of Professor Gordon McVie, Founder of ecancer, Dr Beatriz Amendola, President of the symposium and Dr Jorge Jimenez, President of Foro Nacional de Cancer Chile, and former Minister of Health. PMID- 27563354 TI - A web-based interactive tool to improve breast cancer patient centredness. AB - The uniqueness of a patient as determined by the integration of clinical data and psychological aspects should be the aspired aim of a personalized medicine approach. Nevertheless, given the time constraints usually imposed by the clinical setting, it is not easy for physicians to collect information about the patient's unique mental dimensions and needs related to her illness. Such information may be useful in tailoring patient-physician communication, improving the patient's understanding of provided information, her involvement in the treatment process, and in general her empowerment during and after the therapeutic journey. The primary objective of this study is to evaluate the effect of an interactive empowerment tool (IEm) on enhancing the breast cancer patient-physician experience, in terms of increasing empowerment, i.e. by providing physicians with a personalised patient's profile, accompanied by specific recommendations to advise them how to interact with each individual patient on the basis of her personal profile. The study will be implemented as a two-arm randomised controlled trial with 100 adult breast cancer patients who fill in the ALGA-BC questionnaire, a computerised validated instrument to evaluate the patient's physical and psychological characteristics following a breast cancer diagnosis. The IEm tool will collect and analyse the patient's answers in real time and send them, together with specific recommendations to the physician's computer immediately before physician's first encounter with the patient. Patients will be randomised to either the intervention group using the IEm tool or to a control group who will only fill in the questionnaire without taking advantage of the tool (physicians will not receive the patient's profile). The proposed approach is supposed to improve the patient-physician communication leading to increased patient participation in the therapeutic process as a consequence leading to improvement in patient empowerment and personalisation of care. PMID- 27563355 TI - beta-Cell death is decreased in women with gestational diabetes mellitus. AB - BACKGROUND: Gestational diabetes mellitus (GDM) affects approximately 7-17 % of all pregnancies and has been recognized as a significant risk factor to neonatal and maternal health. Postpartum, GDM significantly increases the likelihood of developing type 2 diabetes (T2D). While it is well established that insulin resistance and impaired beta-cell function contribute to GDM development, the role of active beta-cell loss remains unknown. Differentially methylated circulating free DNA (cfDNA) is a minimally invasive biomarker of beta-cell loss in type 1 diabetes mellitus. Here we use cfDNA to examine the levels of beta-cell death in women with GDM. METHODS: Second to third-trimester pregnant women with GDM were compared with women with normal pregnancy (PRG), women at postpartum (PP), and non-pregnant (NP) women. Fasting glucose levels, insulin, and C-peptide levels were measured. Serum samples were collected and cfDNA purified and bisulfite treated. Methylation-sensitive probes capable of differentiating between beta-cell-derived DNA (demethylated) and non-beta-cell-derived DNA (methylated) were used to measure the presence of beta-cell loss in the blood. RESULTS: GDM was associated with elevated fasting glucose levels (GDM = 185.9 +/- 5.0 mg/dL) and reduced fasting insulin and c-peptide levels when compared with NP group. Interestingly, beta-cell derived insulin DNA levels were significantly lower in women with GDM when compared with PRG, NP, and PP groups (demethylation index: PRG = 7.74 * 10(-3) +/- 3.09 * 10(-3), GDM = 1.01 * 10(-3) +/- 5.86 * 10( 4), p < 0.04; NP = 4.53 * 10(-3) +/- 1.62 * 10(-3), PP = 3.24 * 10(-3) +/- 1.78 * 10(-3)). CONCLUSIONS: These results demonstrate that beta-cell death is reduced in women with GDM. This reduction is associated with impaired insulin production and hyperglycemia, suggesting that beta-cell death does not contribute to GDM during the 2nd and 3rd trimester of pregnancy. PMID- 27563357 TI - A spectral optical flow method for determining velocities from digital imagery. AB - We present a method for determining surface flows from solar images based upon optical flow techniques. We apply the method to sets of images obtained by a variety of solar imagers to assess its performance. The opflow3d procedure is shown to extract accurate velocity estimates when provided perfect test data and quickly generates results consistent with completely distinct methods when applied on global scales. We also validate it in detail by comparing it to an established method when applied to high-resolution datasets and find that it provides comparable results without the need to tune, filter or otherwise preprocess the images before its application. PMID- 27563356 TI - Building Evidence-Based Tobacco Treatment in the Eastern Mediterranean Region: Lessons Learned by the Syrian Center for Tobacco Studies. AB - The tobacco epidemic in Syria is characterized by high rates of cigarettes smoking in men and dramatic reemergence of waterpipe smoking, especially among youths and women. The Syrian Center for Tobacco Studies (SCTS), an NIH-funded pioneer research and capacity building institution, has developed a research infrastructure and conducted three randomized clinical trials to develop and rigorously test culturally-appropriate tobacco treatment programs integrated into primary healthcare (PHC) centers. This review aimed to discuss challenges and lessons learned from the Syrian experience. Addressing these challenges may inform future cessation research activities in Syria and other developing countries. To develop a research infrastructure, the SCTS has established Syria's first IRB and trained physicians/medical students in both tobacco treatment and research methods. Main challenges to conduct the cessation trials were difficulties of coordination between the local and international collaborators; high Smoking Rates among PHC providers; lack of pharmacological agents used in tobacco treatment; and difficulties of conducting research in a politically volatile region. Strategies to overcome these challenges were ensuring an active and regular involvement of all investigator; and advocating for a national smoking-cessation plan that involves training health care providers in smoking cessation treatment and make pharmacological agents used in smoking cessation available. PMID- 27563358 TI - Toward Self-Referential Autonomous Learning of Object and Situation Models. AB - Most current approaches to scene understanding lack the capability to adapt object and situation models to behavioral needs not anticipated by the human system designer. Here, we give a detailed description of a system architecture for self-referential autonomous learning which enables the refinement of object and situation models during operation in order to optimize behavior. This includes structural learning of hierarchical models for situations and behaviors that is triggered by a mismatch between expected and actual action outcome. Besides proposing architectural concepts, we also describe a first implementation of our system within a simulated traffic scenario to demonstrate the feasibility of our approach. PMID- 27563359 TI - From Spin to Swindle: Identifying Falsification in Financial Text. AB - Despite legislative attempts to curtail financial statement fraud, it continues unabated. This study makes a renewed attempt to aid in detecting this misconduct using linguistic analysis with data mining on narrative sections of annual reports/10-K form. Different from the features used in similar research, this paper extracts three distinct sets of features from a newly constructed corpus of narratives (408 annual reports/10-K, 6.5 million words) from fraud and non-fraud firms. Separately each of these three sets of features is put through a suite of classification algorithms, to determine classifier performance in this binary fraud/non-fraud discrimination task. From the results produced, there is a clear indication that the language deployed by management engaged in wilful falsification of firm performance is discernibly different from truth-tellers. For the first time, this new interdisciplinary research extracts features for readability at a much deeper level, attempts to draw out collocations using n grams and measures tone using appropriate financial dictionaries. This linguistic analysis with machine learning-driven data mining approach to fraud detection could be used by auditors in assessing financial reporting of firms and early detection of possible misdemeanours. PMID- 27563360 TI - Multilingual Sentiment Analysis: State of the Art and Independent Comparison of Techniques. AB - With the advent of Internet, people actively express their opinions about products, services, events, political parties, etc., in social media, blogs, and website comments. The amount of research work on sentiment analysis is growing explosively. However, the majority of research efforts are devoted to English language data, while a great share of information is available in other languages. We present a state-of-the-art review on multilingual sentiment analysis. More importantly, we compare our own implementation of existing approaches on common data. Precision observed in our experiments is typically lower than the one reported by the original authors, which we attribute to the lack of detail in the original presentation of those approaches. Thus, we compare the existing works by what they really offer to the reader, including whether they allow for accurate implementation and for reliable reproduction of the reported results. PMID- 27563361 TI - Nutritional Alterations Associated with Neurological and Neurosurgical Diseases. AB - Neurological and neurosurgical diseases lead to complications producing malnutrition increasing pathology and mortality. In order to avoid complications because of malnutrition or overcome deficiencies in nutrients supplements are often used for these subjects. The physiopathological mechanisms of malnutrition, methods of nutritional assessment and the supplemental support are reviewed in this paper based on the assumption that patients need to receive adequate nutrition to promote optimal recovery, placing nutrition as a first line treatment and not an afterthought in the rehabilitation. PMID- 27563363 TI - OHRQoL in a Sample of Alcohol and Drug Abusers. AB - AIMS: To determine oral health related quality of life (OHRQoL) in a large sample of substance abusers and to evaluate the effect of dental treatment on OHRQoL. DESIGN: A longitudinal observational study. SETTINGS: A dental care clinic specialized in treating severely addicted patients. PARTICIPANTS: A sample of severely addicted substance abusers. MEASUREMENTS: OHRQoL was measured using the OHIP-14, which was filled out at baseline (T0), prior to the first treatment session (T1), after about 6 treatment sessions (T2) and on the last day of treatment (T3). FINDINGS: Mean OHIP scores did not change from T0 to T1. At T1, a mean OHIP-14 total score = 37.1 (sd=12.4, N = 392) was found. The highest mean scores were observed for the subscales physical pain and psychological discomfort. Data from 129 patients was available on both T1 and T2. The mean OHIP 14 total score reduced significantly (mean difference = 5.63, 95% CI 3.76 - 7.51), t(128)=5.94, p <0.001. The highest reduction in mean score was found for the subscale physical pain (mean difference = 1.24, 95%CI 0.81 - 1.66). Also between T2 and T3 a significant reduction in OHIP-14 total score (mean difference = 2.41, 95%CI 0.06-4.76) took place. CONCLUSION: The oral health status of substance abusers does have a substantial effect on their quality of life, which can be improved to a great extent by dental treatment based on a model tailored to addicted patients. PMID- 27563362 TI - Potential Role of Caffeine in the Treatment of Parkinson's Disease. AB - Parkinson's disease [PD] is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of alpha-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from both in vivo and in vitro studies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2A receptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials. PMID- 27563364 TI - Lower Extremity Near-infrared Spectroscopy After Popliteal Block For Orthopaedic Foot Surgery. AB - BACKGROUND: Noninvasive measurement of cutaneous tissue oxygenation using near infrared spectroscopy (NIRS) has become common in peri-operative care. Following institution of peripheral nerve blocks, neurovascular alterations in the blocked region have been described. OBJECTIVE: The primary aim of this study encompassed the assessment of the influence of a popliteal block on changes in regional oxygen saturation (SrO2), and the location of most prominent changes. METHOD: We conducted a prospective randomised controlled trial. Hundred twenty patients who received a popliteal block for foot surgery were included. Popliteal block was performed under echographic guidance. The patients were randomized in 3 groups according to the location of the SrO2 electrodes on the legs. Bilateral SrO2 measurements were performed simultaneously. SrO2 in the operated leg and in the control leg was measured at baseline and 1, 5, 10, 15, and 30 minutes after the perineural injection. We quantified the evolution in SrO2 by calculating over time the differences in SrO2 values between the operated and control leg (=DeltaSrO2). RESULTS: At 30 minutes, DeltaSrO2 increased significantly (p<0.05) at the plantar side of the foot (11.3% +/- 2.9%), above the ankle (4.9% +/- 1.3%) and the popliteal fossa (3.6% +/- 1.2%). CONCLUSION: At 30 minutes after institution of the popliteal block, DeltaSrO2 was most prominent at the plantar side of the foot as compared with measurement performed above the ankle or under the knee. PMID- 27563365 TI - Anatomic Versus Mechanically Aligned Total Knee Arthroplasty for Unicompartmental Knee Arthroplasty Revision. AB - OBJECTIVES: The purpose of this study was to compare the intra-operative benefits and the clinical outcomes from kinematic or mechanical alignment for total knee arthroplasty (TKA) in patients undergoing revision of failed unicompartmental kneel arthroplasty (UKA) to TKA. METHODS: Ten revisions were performed with a kinematic alignment technique and 11 with a mechanical alignment. Measurements of the hip-knee-ankle angle (HKA), the lateral distal femoral angle (LDFA), and the medial proximal tibial angle (MPTA) were performed using long-leg radiographs. The need for augments, stems, and constrained inserts was compared between groups. Clinical outcomes were compared using the WOMAC score along with maximum distance walked as well as knee range of motion obtained prior to discharge. All data was obtained by a retrospective review of patient files. RESULTS: The kinematic group required less augments, stems, and constrained inserts than the mechanical group and thinner polyethylene bearings. There were significant differences in the lateral distal femoral angle (LDFA) and the medial proximal tibial angle (MPTA) between the two groups (p<0.05). The mean WOMAC score obtained at discharge was better in the kinematic group as was mean knee flexion. At last follow up of 34 months for the kinematic group and 58 months for the mechanical group, no orthopedic complications or reoperations were recorded. CONCLUSION: Although this study has a small patient cohort, our results suggest that kinematic alignment for TKA after UKA revision is an attractive method. Further studies are warranted. PMID- 27563367 TI - Quality Partitioned Meshing of Multi-Material Objects. AB - We present a simple but effective algorithm for generating topologically and geometrically consistent quality triangular surface meshing of compactly packed multiple heterogeneous domains in [Formula: see text]. By compact packing we imply that adjacent homogeneous domains or materials share some 0, 1, and/or 2 dimensional boundary. Such packed multiple material (or multi-material) solids arise naturally from classification/partitioning/segmentation of homogeneous domains in [Formula: see text] into different sub-regions. The multi-materials may also represent separate functionally classified sections or just be multiple component copies tightly fused together as perhaps by layered manufacturing processes. The input to our algorithm is a geometric representation of the entire multi-material solid, and a volumetric classification map identifying the individual materials. As output, each individual material region is represented by a triangulated 2-manifold boundary, with adjacent material regions having shared boundaries. Our algorithm has been implemented, and applied to different multi-material solids, and the results are additionally presented with quantitative analysis of detection and cure of non-manifold interfaces as well as spurious small components. These meshes are useful for combined boundary element analysis, however these simulation results are not presented. PMID- 27563366 TI - Exploratory Analysis for the Evaluation of Estimated Glomerular Filtration Rate, Cholesterol and Triglycerides after Switching from Tenofovir/Emtricitabine plus Atazanavir/Ritonavir (ATV/r) to Abacavir/Lamivudine plus ATV/r in Patients with Preserved Renal Function. AB - BACKGROUND AND OBJECTIVES: Renal toxicity due to tenofovir (TDF) has been largely described in patients with HIV infection. However, other antiretroviral drugs (such as atazanavir [ATV], especially when boosted by ritonavir, ATV/r) could perpetuate some degrees of renal impairment with or without TDF co administration. Also, possible benefits of stopping TDF in patients without renal diseases is not well known. This study aimed at exploring evolution of renal function and lipid profile after switching from tenofovir/emtricitabine (TDF/FTC) to abacavir/lamivudine (ABC/3TC), maintaining the ATV/r component of the regimen. METHODS: Patients in the Italian MASTER Cohort, who switched from TDF/FTC plus ATV/r to ABC/3TC plus ATV/r were included, provided that major renal diseases were not diagnosed before switching (i.e., baseline). Serum creatinine, estimated glomerular filtration rate (eGFR), total cholesterol, HDL and triglycerides were evaluated at baseline and at month 18 after switching. RESULTS: 126 patients were selected (80% males). Patients were mostly Italians (92%). 79% had undetectable HIV-RNA and 44% were co-infected by HBV and/or HCV. Median age at switch was 47 years (IQR 43-55). A small but significant decrease in serum creatinine [from 1.06 mg/dl (SD: 0.3) to 0.94 mg/dl (SD: 0.2); p<0.001] with an improvement in eGFR [from 86.8 ml/min (SD: 33) to 96.4 ml/min (SD: 37); p<0.001] were observed in per protocol analysis at month 18. Also ITT analysis showed a decrease in mean serum creatinine [from 1.08 mg/dl (SD: 0.35) to 0.95 mg/dl (SD: 0.24); p<0.001] with an improvement in mean eGFR [from 86.9 ml/min/1.73m2 (SD: 24.11) to 95.8 ml/min/1.73m2 (SD: 19.99); p<0.001]. Total cholesterol increased [from 188 mg/dl (SD: 42) to 206 mg/dl (SD: 44); p<0.001] but also HDL increased as well [from 46 mg/dl (SD: 14) to 54 mg/dl (SD: 19); p=0.015]. An increase in triglycerides concentration was observed [from 162 mg/dl (SD: 144) to 214 mg/dl (SD: 109); p=0.027] in per protocol analysis. Also ITT analysis showed increases of both total cholesterol [from 187 mg/dl (SD: 43.69) to 203 mg/dl (SD: 44.10); p<0.001] and HDL fraction [from 46 mg/dl (SD: 15.49) to 52 mg/dl (SD: 17.13); p=0.002] at month 18. CONCLUSION: This analysis reports an improvement in eGFR and an increase in total cholesterol and HDL fraction at month 18 after switching to ABC/3TC plus ATV/r. Given the fact that renal function was not significantly affected at baseline, our findings may suggest the utility of a proactive switch from TDF to ABC, when otherwise indicated, in patients who cannot avoid using a nucleoside backbone. PMID- 27563368 TI - Highly Symmetric and Congruently Tiled Meshes for Shells and Domes. AB - We describe the generation of all possible shell and dome shapes that can be uniquely meshed (tiled) using a single type of mesh face (tile), and following a single meshing (tiling) rule that governs the mesh (tile) arrangement with maximal vertex, edge and face symmetries. Such tiling arrangements or congruently tiled meshed shapes, are frequently found in chemical forms (fullerenes or Bucky balls, crystals, quasi-crystals, virus nano shells or capsids), and synthetic shapes (cages, sports domes, modern architectural facades). Congruently tiled meshes are both aesthetic and complete, as they support maximal mesh symmetries with minimal complexity and possess simple generation rules. Here, we generate congruent tilings and meshed shape layouts that satisfy these optimality conditions. Further, the congruent meshes are uniquely mappable to an almost regular 3D polyhedron (or its dual polyhedron) and which exhibits face-transitive (and edge-transitive) congruency with at most two types of vertices (each type transitive to the other). The family of all such congruently meshed polyhedra create a new class of meshed shapes, beyond the well-studied regular, semi regular and quasi-regular classes, and their duals (platonic, Catalan and Johnson). While our new mesh class is infinite, we prove that there exists a unique mesh parametrization, where each member of the class can be represented by two integer lattice variables, and moreover efficiently constructable. PMID- 27563369 TI - Inadequate Sleep as a Mediating Variable between Exposure to Interparental Violence and Depression Severity in Adolescents. AB - Exposure to violence, including interparental and peer dating violence, is a public health concern associated with negative outcomes, including depression. However, little is known about mechanisms by which exposure to violence influences depressive symptoms. One factor that may help explain this association is problematic sleep. This study sought to determine whether short sleep duration mediates the relationship between exposure to violence (interparental and peer dating violence) and depressive symptoms. Structural equation modeling was used to examine the mediating role of short sleep duration from a 3-year longitudinal study of 1,042 high school students. Results demonstrated interparental violence was negatively related to sleep duration (friends dating violence was not), and sleep duration negatively associated with depressive symptoms. Adolescents exposed to violence between their parents obtained less sleep on school nights. In turn, they reported more depressive symptoms. Short sleep duration mediated the relationship between exposure to interparental violence and depression severity. PMID- 27563370 TI - Pilomatrixoma Arising Juxtaposed to Congenital Melanocytic Nevi: Concern for Malignant Degeneration? A Previously Unreported Association. PMID- 27563371 TI - Acute Marjolin's Ulcer Arising in a Split-Thickness Skin Graft Postburn Injury. PMID- 27563372 TI - Posterior, Extended, Pedicled Latissimus Dorsi Flap for the Reconstruction of a Large Complicated Lower Back Wound. PMID- 27563373 TI - Square Root Graphical Models: Multivariate Generalizations of Univariate Exponential Families that Permit Positive Dependencies. AB - We develop Square Root Graphical Models (SQR), a novel class of parametric graphical models that provides multivariate generalizations of univariate exponential family distributions. Previous multivariate graphical models (Yang et al., 2015) did not allow positive dependencies for the exponential and Poisson generalizations. However, in many real-world datasets, variables clearly have positive dependencies. For example, the airport delay time in New York-modeled as an exponential distribution-is positively related to the delay time in Boston. With this motivation, we give an example of our model class derived from the univariate exponential distribution that allows for almost arbitrary positive and negative dependencies with only a mild condition on the parameter matrix-a condition akin to the positive definiteness of the Gaussian covariance matrix. Our Poisson generalization allows for both positive and negative dependencies without any constraints on the parameter values. We also develop parameter estimation methods using node-wise regressions with l1 regularization and likelihood approximation methods using sampling. Finally, we demonstrate our exponential generalization on a synthetic dataset and a real-world dataset of airport delay times. PMID- 27563375 TI - HIV-1 Tat Regulates Occludin and Abeta Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway. AB - HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Abeta) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining. The mRNA levels of occludin, RAGE, and LRP1 were measured using quantitative real-time polymerase chain reaction. HIV-1 Tat at 1 ug/mL and the Rho inhibitor hydroxyfasudil (HF) at 30 umol/L, with 24 h exposure, had no significant effect on hCMEC/D3 cell viability. Treatment with HIV-1 Tat protein decreased mRNA and protein levels of occludin and LRP1 and upregulated the expression of RAGE; however, these effects were attenuated by HF. These data suggest that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-mediated changes in occludin, RAGE, and LRP1 in hCMEC/D3 cells. HF may have a beneficial influence by protecting the integrity of the blood-brain barrier and the expression of Abeta transfer receptors. PMID- 27563377 TI - Editors' Note. AB - The Spring 2015 issue of the International Journal of Telerehabilitation (IJT) contains original research that analyzes provider perspectives on the use of telepractice to serve the families of children who are deaf or hard of hearing. Two case studies examine the utility of administering Facial Affect Training through telepractice to individuals with chronic traumatic brain injury. An article in IJT's policy section describes the process for the formulation of the World Federation of Occupational Therapists (WFOT) international telehealth position statement for occupational therapy. The World Federation of Occupational Therapists (WFOT) consists of 84 member organizations representing over 420,000 occupational therapists internationally (WFOT, 2014). The Spring 2015 issue also contains announcements of upcoming conferences. As of May 2015, the International Journal of Telerehabilitation (IJT) is live on PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/journals/2411/. Articles from all past issues were indexed, as will be the current and future issues. PMID- 27563378 TI - Provider Perspectives on Telepractice for Serving Families of Children Who are Deaf or Hard of Hearing. AB - Telepractice to deliver remote Part C early intervention (EI) services to families in their home is a rapidly-growing strategy under the Individuals with Disabilities Education Act (IDEA) to meet the needs of infants and toddlers who are deaf or hard of hearing. A survey was completed within a "learning community" comprised of staff from EI programs that were implementing telepractice to learn about their specific implementation strategies and challenges they faced. Twenty seven individuals representing 11 programs responded. The results showed great variability in hardware and software, with many raising concerns regarding security. Primary challenges reported were internet connectivity and training in skills required to deliver telepractice services. The findings from this survey were valuable in guiding future areas of investigation for the learning community and ultimately improving telepractice in the field. PMID- 27563374 TI - Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches. AB - The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context. PMID- 27563379 TI - Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury. AB - The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI). The modified FAR training was administered via telepractice to target social communication skills. Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play. Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication. Both participants with chronic TBI showed gains on identifying facial emotions on the static photos. PMID- 27563376 TI - Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review. AB - Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD. PMID- 27563380 TI - The Process for the Formulation of the International Telehealth Position Statement for Occupational Therapy. AB - The World Federation of Occupational Therapists (WFOT) consists of 84 member organizations representing over 420,000 occupational therapists internationally (WFOT, 2014). In 2014, WFOT published the WFOT Telehealth Position Statement on the use of telehealth in occupational therapy. The process for the formulation of the official document involved reviewing WFOT member organizations' telehealth position statements and data collected from a survey sent to member organizations' delegates in April 2014. Qualitative data from 39 countries yielded factors to consider in five key areas: licensure/registration requirements, the cost of technology, privacy and security, reimbursement/payment models, and other issues (e.g., need for collaboration/transfer of knowledge, client selection, provider competencies, standard of care). The WFOT Telehealth Position Statement addressed each of these areas. The collaborative effort resulting in the development of the WFOT Telehealth Position Statement serves as a model for other international organizations. PMID- 27563381 TI - Editors' Note. AB - The Fall 2015 issue of the International Journal of Telerehabilitation (IJT) presents original articles in the areas of Research; Privacy and Security; and Technology Review. As of May 2015, the International Journal of Telerehabilitation (IJT) is live on PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/journals/2411/. Articles from all past issues are indexed, as will be the current and future issues. PMID- 27563382 TI - Consumer Satisfaction with Telerehabilitation Service Provision of Alternative Computer Access and Augmentative and Alternative Communication. AB - Telerehabilitation (TR) services for assistive technology evaluation and training have the potential to reduce travel demands for consumers and assistive technology professionals while allowing evaluation in more familiar, salient environments for the consumer. Sixty-five consumers received TR services for augmentative and alternative communication or alternative computer access, and consumer satisfaction was compared with twenty-eight consumers who received exclusively in-person services. TR recipients rated their TR services at a median of 6 on a 6-point Likert scale TR satisfaction questionnaire, although individual responses did indicate room for improvement in the technology. Overall satisfaction with AT services was rated highly by both in-person (100% satisfaction) and TR (99% satisfaction) service recipients. PMID- 27563383 TI - Protocol for a Systematic Review of Telehealth Privacy and Security Research to Identify Best Practices. AB - Healthcare professionals engaged in telehealth are faced with complex US federal regulations (e.g., HIPAA/HITECH) and could benefit from the guidance provided by best practices in Privacy and Security (P&S). This article describes a systematic review protocol to address this need. The protocol described herein uses the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The PRISMA-P contains 17 items that are considered essential, as well as minimum components to include in systematic reviews. PICOS (participants, interventions, comparisons, outcome(s) and study design of the systematic review) are also relevant to the development of best practices in P&S in telehealth systems. A systematic process can best determine what information should be included and how this information should be retrieved, condensed, analyzed, organized, and disseminated. PMID- 27563385 TI - Editors' Note. AB - The Spring 2016 issue of the International Journal of Telerehabilitation (IJT) presents original and innovative work in three diverse sections: usability, intervention, and pedagogy, followed by a book review on teleaudiology. The contributors to this issue are notably multi-disciplinary and include an audiologist, computer scientists, engineers, an epidemiologist, occupational therapists, a rehabilitation counselor, a physician (physical medicine and rehabilitation), and speechlanguage pathologists. The common thread linking the Journal's authors and their manuscripts, is excellence in telerehabilitation related innovation. PMID- 27563384 TI - Feasibility of a Customized, In-Home, Game-Based Stroke Exercise Program Using the Microsoft Kinect(r) Sensor. AB - The objective of this study was to determine the feasibility of a 6-week, game based, in-home telerehabilitation exercise program using the Microsoft Kinect(r) for individuals with chronic stroke. Four participants with chronic stroke completed the intervention based on games designed with the customized Mystic Isle software. The games were tailored to each participant's specific rehabilitation needs to facilitate the attainment of individualized goals determined through the Canadian Occupational Performance Measure. Likert scale questionnaires assessed the feasibility and utility of the game-based intervention. Supplementary clinical outcome data were collected. All participants played the games with moderately high enjoyment. Participant feedback helped identify barriers to use (especially, limited free time) and possible improvements. An in-home, customized, virtual reality game intervention to provide rehabilitative exercises for persons with chronic stroke is practicable. However, future studies are necessary to determine the intervention's impact on participant function, activity, and involvement. PMID- 27563386 TI - Development of the Telehealth Usability Questionnaire (TUQ). AB - Current telehealth usability questionnaires are designed primarily for older technologies, where telehealth interaction is conducted over dedicated videoconferencing applications. However, telehealth services are increasingly conducted over computer-based systems that rely on commercial software and a user supplied computer interface. Therefore, a usability questionnaire that addresses the changes in telehealth service delivery and technology is needed. The Telehealth Usability Questionnaire (TUQ) was developed to evaluate the usability of telehealth implementation and services. This paper addresses: (1) the need for a new measure of telehealth usability, (2) the development of the TUQ, (3) intended uses for the TUQ, and (4) the reliability of the TUQ. Analyses indicate that the TUQ is a solid, robust, and versatile measure that can be used to measure the quality of the computer-based user interface and the quality of the telehealth interaction and services. PMID- 27563387 TI - Iterative Design and Usability Testing of the Imhere System for Managing Chronic Conditions and Disability. AB - A novel mobile health platform, Interactive Mobile Health and Rehabilitation (iMHere), is being developed to support wellness and self-management among people with chronic disabilities. The iMHere system currently includes a smartphone app with six modules for use by persons with disabilities and a web portal for use by medical and rehabilitation professionals or other support personnel. Our initial clinical research applying use of this system provides insight into the feasibility of employing iMHere in the development of self-management skills in young adults (ages 18-40 years) with spina bifida (SB) (Dicianno, Fairman, et al., 2015). This article describes the iterative design of the iMHere system including usability testing of both the app modules and clinician portal. Our pilot population of persons with SB fostered the creation of a system appropriate for people with a wide variety of functional abilities and needs. As a result, the system is appropriate for use by persons with various disabilities and chronic conditions, not only SB. In addition, the diversity of professionals and support personnel involved in the care of persons with SB also enabled the design and implementation of the iMHere system to meet the needs of an interdisciplinary team of providers who treat various conditions. The iMHere system has the potential to foster communication and collaboration among members of an interdisciplinary healthcare team, including individuals with chronic conditions and disabilities, for a client-centered approach to support self-management skills. PMID- 27563388 TI - An Exploratory Investigation of E-Rest: Teletherapy for Chronically Aphasic Speakers. AB - Delivering aphasia therapy via telecommunication may provide a means to deliver intensive therapy in a cost-effective way. Teletherapy, remotely-administered (language) treatment, may support the repetitive drill practices that people with chronic aphasia need to perform when learning to compensate for their lasting language difficulties. The use of teletherapy may allow speech and language pathologists (SLPs) to focus in-person sessions more strongly on the generalisation of therapy effects to daily life. This single subject study is an investigation whether a teletherapy application called e-REST meets the criteria of accessibility, user-friendliness, as well as effectiveness. e-REST, the teletherapy version of the Dutch and adapted Reduced Syntax Therapy, teaches chronically aphasic speakers of Dutch who experience difficulties in sentence production to convey their messages in a kind of telegraphic style. The results obtained suggest that it is reasonable to conduct a larger study into the user friendliness, accessibility, effectiveness, and cost-effectiveness of e-REST. PMID- 27563389 TI - Occupational Therapy Home Safety Intervention via Telehealth. AB - Photography can be an effective addition for education-based telehealth services delivered by an occupational therapist. In this study, photography was used as antecedent to telehealth sessions delivered by an occupational therapist focused on narrative learning about home safety. After taking photographs of past home safety challenges, six participants experienced three web-based occupational therapy sessions. Sessions were recorded and transcribed. Data were examined using content analysis. The content analysis identified the following themes: the value of photos to support learning; the value of narrative learning related to home safety education; and abstract versus concrete learners. Procedural findings are included to support future endeavors. Findings indicate that within a wellness context, home safety education for older adults can be delivered effectively via telehealth when using photography as a part of an occupational therapy intervention. PMID- 27563390 TI - A Pedagogical Note: Use of Telepractice to Link Student Clinicians to Diverse Populations. AB - Telepractice is the application of telecommunications technology to the delivery of telehealth services via the online connection of clinicians, clients, and patients for assessment, intervention, or consultation. This article describes a pilot project in which speech-language pathology students in a university training program gained experience in working with culturally diverse preschool students using telepractice technology. The preschool students benefited by making gains in communication skills, while the university students acquired competency in the use of telepractice and in working with children whose cultural and linguistic backgrounds were outside of their experience. To assess the training experience, a Likert-scale survey administered to student clinicians revealed a high degree of satisfaction and improved familiarity with the use of telepractice, and an increased comfort level working with multi-cultural populations. PMID- 27563391 TI - PROBABILISTIC FIBER TRACKING USING A MODIFIED LASSO BOOTSTRAP METHOD. AB - Diffusion MRI (dMRI) provides a noninvasive tool for investigating white matter tracts. Probabilistic fiber tracking has been proposed to represent the fiber structures as 3D streamlines while taking the uncertainty introduced by noise into account. In this paper, we propose a probabilistic fiber tracking method based on bootstrapping a multi-tensor model with a fixed tensor basis. The fiber orientation (FO) estimation is formulated as a Lasso problem. Then by resampling the residuals calculated using a modified Lasso estimator to create synthetic diffusion signals, a distribution of FOs is estimated. Probabilistic fiber tracking can then be performed by sampling from the FO distribution. Experiments were performed on a digital crossing phantom and brain dMRI for validation. PMID- 27563392 TI - Targeting the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein for the Treatment of Cystic Fibrosis. PMID- 27563393 TI - Inhibitors of BRD4 as Potential Cancer Therapy. PMID- 27563394 TI - Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket. AB - Mixed lineage leukemia (MLL) gene rearrangement induces leukemic transformation by ectopic recruitment of disruptor of telomeric silencing 1-like protein (DOT1L), a lysine histone methyltransferase, leading to local hypermethylation of H3K79 and misexpression of genes (including HoxA), which drive the leukemic phenotype. A weak fragment-based screening hit identified by SPR was cocrystallized with DOT1L and optimized using structure-based ligand optimization to yield compound 8 (IC50 = 14 nM). This series of inhibitors is structurally not related to cofactor SAM and is not interacting within the SAM binding pocket but induces a pocket adjacent to the SAM binding site. PMID- 27563395 TI - Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach. AB - Oncogenic MLL fusion proteins aberrantly recruit Dot1L, a histone methyltransferase, to ectopic loci, leading to local hypermethylation of H3K79 and misexpression of HoxA genes driving MLL-rearranged leukemias. Inhibition of the methyltransferase activity of Dot1L in this setting is predicted to reverse aberrant H3K79 methylation, leading to repression of leukemogenic genes and tumor growth inhibition. In the context of our Dot1L drug discovery program, high throughput screening led to the identification of 2, a weak Dot1L inhibitor with an unprecedented, induced pocket binding mode. A medicinal chemistry campaign, strongly guided by structure-based consideration and ligand-based morphing, enabled the discovery of 12 and 13, potent, selective, and structurally completely novel Dot1L inhibitors. PMID- 27563396 TI - Modulation of Backbone Flexibility for Effective Dissociation of Antibacterial and Hemolytic Activity in Cyclic Peptides. AB - Bacterial resistance to antibiotic therapy is on the rise and threatens to evolve into a worldwide emergency: alternative solutions to current therapies are urgently needed. Cationic amphipathic peptides are potent membrane-active agents that hold promise as the next-generation therapy for multidrug-resistant infections. The peptides' behavior upon encountering the bacterial cell wall is crucial, and much effort has been dedicated to the investigation and optimization of this amphipathicity-driven interaction. In this study we examined the interaction of a novel series of nine-membered flexible cyclic AMPs with liposomes mimicking the characteristics of bacterial membranes. Employed techniques included circular dichroism and marker release assays, as well as microbiological experiments. Our analysis was aimed at correlating ring flexibility with their antimicrobial, hemolytic, and membrane activity. By doing so, we obtained useful insights to guide the optimization of cyclic antimicrobial peptides via modulation of their backbone flexibility without loss of activity. PMID- 27563397 TI - Investigation of Proposed Activity of Clarithromycin at GABAA Receptors Using [(11)C]Flumazenil PET. AB - Clarithromycin is a potential treatment for hypersomnia acting through proposed negative allosteric modulation of GABAA receptors. We were interested whether this therapeutic benefit might extend to Parkinson's disease (PD) patients because GABAergic neurotransmission is implicated in postural control. Prior to initiating clinical studies in PD patients, we wished to better understand clarithromycin's mechanism of action. In this work we investigated whether the proposed activity of clarithromycin at the GABAA receptor is associated with the benzodiazepine binding site using in vivo [(11)C]flumazenil positron emission tomography (PET) in primates and ex vivo [(3)H]flumazenil autoradiography in rat brain. While the studies demonstrate that clarithromycin does not change the K d of FMZ, nor does it competitively displace FMZ, there is preliminary evidence from the primate PET imaging studies that clarithromycin delays dissociation and washout of flumazenil from the primate brain in a dose-dependent fashion. These findings would be consistent with the proposed GABAA allosteric modulator function of clarithromycin. While the results are only preliminary, further investigation of the interaction of clarithromycin with GABA receptors and/or GABAergic medications is warranted, and therapeutic applications of clarithromycin alone or in combination with flumazenil, to treat hyper-GABAergic status in PD at minimally effective doses, should also be pursued. PMID- 27563398 TI - Synthesis and Antitubercular Activity of New Benzo[b]thiophenes. AB - In vitro and ex vivo efficacies of four series of benzo[b]thiophene-2-carboxylic acid derivatives were studied against Mycobacterium tuberculosis H37Ra (MTB). Benzo[b]thiophenes were also tested in vitro against multidrug resistant Mycobacterium tuberculosis H37Ra (MDR-MTB), and 7b was found to be highly active against A- and D-MDR-MTB/MTB (MIC ranges 2.73-22.86 MUg/mL). The activity of all benzo[b]thiophenes against M. bovis BCG (BCG) was also assessed grown under aerobic and under conditions of oxygen depletion. Compounds 8c and 8g showed significant activity with MICs of 0.60 and 0.61 MUg/mL against dormant BCG. The low cytotoxicity and high selectivity index data against human cancer cell lines, HeLa, Panc-1, and THP-1 indicate the potential importance of the development of benzo[b]thiophene-based 1,3-diketones and flavones as lead candidates to treat mycobacterial infections. Molecular docking studies into the active site of DprE1 (Decaprenylphosphoryl-beta-d-ribose-2'-epimerase) enzyme revealed a similar binding mode to native ligand in the crystal structure thereby helping to understand the ligand-protein interactions and establish a structural basis for inhibition of MTB. In summary, its good activity in in vitro and ex vivo model, as well as its activity against multidrug-resistant M. tuberculosis H37Ra in a potentially latent state, makes 7b an attractive drug candidate for the therapy of tuberculosis. PMID- 27563399 TI - Stereochemistry Balances Cell Permeability and Solubility in the Naturally Derived Phepropeptin Cyclic Peptides. AB - Cyclic peptide (CP) natural products provide useful model systems for mapping "beyond-Rule-of-5" (bRo5) space. We identified the phepropeptins as natural product CPs with potential cell permeability. Synthesis of the phepropeptins and epimeric analogues revealed much more rapid cellular permeability for the natural stereochemical pattern. Despite being more cell permeable, the natural compounds exhibited similar aqueous solubility as the corresponding epimers, a phenomenon explained by solvent-dependent conformational flexibility among the natural compounds. When analyzing the polarity of the solution structures we found that neither the number of hydrogen bonds nor the total polar surface area accurately represents the solvation energies of the high and low dielectric conformations. This work adds to a growing number of natural CPs whose solvent-dependent conformational behavior allows for a balance between aqueous solubility and cell permeability, highlighting structural flexibility as an important consideration in the design of molecules in bRo5 chemical space. PMID- 27563400 TI - Discovery and Pharmacological Characterization of Novel Quinazoline-Based PI3K Delta-Selective Inhibitors. AB - Inhibition of the lipid kinase PI3Kdelta is a promising principle to treat B and T cell driven inflammatory diseases. Using a scaffold deconstruction reconstruction strategy, we identified 4-aryl quinazolines that were optimized into potent PI3Kdelta isoform selective analogues with good pharmacokinetic properties. With compound 11, we illustrate that biochemical PI3Kdelta inhibition translates into modulation of isoform-dependent immune cell function (human, rat, and mouse). After oral administration of compound 11 to rats, proximal PD markers are inhibited, and dose-dependent efficacy in a mechanistic plaque forming cell assay could be demonstrated. PMID- 27563401 TI - CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. AB - CZ415, a potent ATP-competitive mTOR inhibitor with unprecedented selectivity over any other kinase is described. In addition to a comprehensive characterization of its activities in vitro, in vitro ADME, and in vivo pharmacokinetic data are reported. The suitability of this inhibitor for studying in vivo mTOR biology is demonstrated in a mechanistic mouse model monitoring mTOR proximal downstream phosphorylation signaling. Furthermore, the compound reported here is the first ATP-competitive mTOR inhibitor described to show efficacy in a semitherapeutic collagen induced arthritis (CIA) mouse model. PMID- 27563402 TI - Selective AKR1C3 Inhibitors Potentiate Chemotherapeutic Activity in Multiple Acute Myeloid Leukemia (AML) Cell Lines. AB - We report the design, synthesis, and evaluation of potent and selective inhibitors of aldo-keto reductase 1C3 (AKR1C3), an important enzyme in the regulatory pathway controlling proliferation, differentiation, and apoptosis in myeloid cells. Combination treatment with the nontoxic AKR1C3 inhibitors and etoposide or daunorubicin in acute myeloid leukemia cell lines, elicits a potent adjuvant effect, potentiating the cytotoxicity of etoposide by up to 6.25-fold and the cytotoxicity of daunorubicin by >10-fold. The results validate AKR1C3 inhibition as a common adjuvant target across multiple AML subtypes. These compounds in coadministration with chemotherapeutics in clinical use enhance therapeutic index and may avail chemotherapy as a treatment option to the pediatric and geriatric population currently unable to tolerate the side effects of cancer drug regimens. PMID- 27563403 TI - Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1. AB - Hint1 has recently emerged to be an important target of interest due to its involvement in the regulation of a broad range of CNS functions including opioid signaling, tolerance, neuropathic pain, and nicotine dependence. A series of inhibitors were rationally designed, synthesized, and tested for their inhibitory activity against hHint1 using isothermal titration calorimetry (ITC). The studies resulted in the development of the first small-molecule inhibitors of hHint1 with submicromolar binding affinities. A combination of thermodynamic and high resolution X-ray crystallographic studies provides an insight into the biomolecular recognition of ligands by hHint1. These novel inhibitors have potential utility as molecular probes to better understand the role and function of hHint1 in the CNS. PMID- 27563404 TI - Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer. AB - After a high-throughput screening campaign identified thioether 1 as an antagonist of the nuclear androgen receptor, a zone model was developed for structure-activity relationship (SAR) purposes and analogues were synthesized and evaluated in a cell-based luciferase assay. A novel thioether isostere, cyclopropane (1S,2R)-27, showed the desired increased potency and structural properties (stereospecific SAR response, absence of a readily oxidized sulfur atom, low molecular weight, reduced number of flexible bonds and polar surface area, and drug-likeness score) in the prostate-specific antigen luciferase assay in C4-2-PSA-rl cells to qualify as a new lead structure for prostate cancer drug development. PMID- 27563405 TI - Aligning Potency and Pharmacokinetic Properties for Pyridine-Based NCINIs. AB - Optimization of pyridine-based noncatalytic site integrase inhibitors (NCINIs) based on compound 2 has led to the discovery of molecules capable of inhibiting virus harboring N124 variants of HIV integrase (IN) while maintaining minimal contribution of enterohepatic recirculation to clearance in rat. Structure activity relationships at the C6 position established chemical space where the extent of enterohepatic recirculation in the rat is minimized. Desymmetrization of the C4 substituent allowed for potency optimization against virus having the N124 variant of integrase. Combination of these lessons led to the discovery of compound 20, having balanced serum-shifted antiviral potency and minimized excretion in to the biliary tract in rat, potentially representing a clinically viable starting point for a new treatment option for individuals infected with HIV. PMID- 27563406 TI - Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors. AB - ATG4B or autophagin-1 is a cysteine protease that cleaves ATG8 family proteins. ATG4B plays essential roles in the autophagosome formation and the autophagy pathway. Herein we disclose the design and structural modifications of a series of fluoromethylketone (FMK)-based peptidomimetics as highly potent ATG4B inhibitors. Their structure-activity relationship (SAR) and protease selectivity are also discussed. PMID- 27563407 TI - Mitochondrial-Targeting MET Kinase Inhibitor Kills Erlotinib-Resistant Lung Cancer Cells. AB - Lung cancer cells harboring activating EGFR mutations acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) by activating several bypass mechanisms, including MET amplification and overexpression. We show that a significant proportion of activated MET protein in EGFR TKI-resistant HCC827 lung cancer cells resides within the mitochondria. Targeting the total complement of MET in the plasma membrane and mitochondria should render these cells more susceptible to cell death and hence provide a means of circumventing drug resistance. Herein, the mitochondrial targeting triphenylphosphonium (TPP) moiety was introduced to the selective MET kinase inhibitor PHA665752. The resulting TPP analogue rapidly localized to the mitochondria of MET-overexpressing erlotinib-resistant HCC827 cells, partially suppressed the phosphorylation (Y1234/Y1235) of MET in the mitochondrial inner membrane and was as cytotoxic and apoptogenic as the parent compound. These findings provide support for the targeting of mitochondrial MET with a TPP-TKI conjugate as a means of restoring responsiveness to chemotherapy. PMID- 27563408 TI - Diverging Novobiocin Anti-Cancer Activity from Neuroprotective Activity through Modification of the Amide Tail. AB - Novobiocin is a natural product that binds the Hsp90 C-terminus and manifests Hsp90 inhibitory activity. Structural investigations on novobiocin led to the development of both anti-cancer and neuroprotective agents. The varied pharmacological activity manifested by these novobiocin analogs prompted the investigation of structure-function studies to identify these contradictory effects, which revealed that modifications to the amide side chain produce either anti-cancer or neuroprotective activity. Compounds that exhibit neuroprotective activity contain a short alkyl or cycloalkyl amide side chain. In contrast, anti cancer agents contain five or more carbons, disrupt interactions between Hsp90alpha and Aha1, and induce the degradation of Hsp90-dependent client proteins. PMID- 27563409 TI - New Generation of Psychotherapies Inspired by Cognitive Neuroscience Development: Emergence of Neurocognitive Therapies. PMID- 27563410 TI - Neuropsychiatric Consequences of Deep Brain Stimulation in Patients with Chronic Movement Disorders. PMID- 27563411 TI - A Review on Brain Stimulation Using Low Intensity Focused Ultrasound. AB - Brain stimulation techniques are important in both basic and clinical studies. Majority of well-known brain stimulating techniques have low spatial resolution or entail invasive processes. Low intensity focused ultrasound (LIFU) seems to be a proper candidate for dealing with such deficiencies. This review recapitulates studies which explored the effects of LIFU on brain structures and its function, in both research and clinical areas. Although the mechanism of LIFU action is still unclear, its different effects from molecular level up to behavioral level can be explored in animal and human brain. It can also be coupled with brain imaging assessments in future research. PMID- 27563412 TI - Papaver Rhoeas L. Hydroalcoholic Extract Exacerbates Forced Swimming Test-Induced Depression in Mice. AB - INTRODUCTION: Depression is one of the most frequent psychiatric disorders in the world with occurs with higher incidence in women. In the present study, the effect of water-alcoholic extract of Papaver rhoeas L. on forced swimming test (FST) in Swiss-Webster mice were examined. METHODS: We used Swiss-Webster mice (20-25 g) to execute FST on them. The plant extract (1, 10, 30, and 100 mg/kg) was injected to the animals 30 minutes before each session. Fluoxetine (20 mg/kg) was used as standard antidepressant drug. In another group of animals, 30 minutes after extract administration, blood samples were taken from retro-orbital sinus for corticosterone assay. Yet in third group, the drugs were injected to the animals and 30 minutes later, their activities were tested in an open field apparatus. RESULTS: Our experiments showed that the extract efficiently reduced FST time both in male and female mice dose-dependently. This effect was comparable with fluoxetine. In addition, corticosterone assay indicated that plasma corticosterone in animals which received extract was higher than those amounts in fluoxetine and saline controls. Moreover, the animals did not show any motor activity deficit in all doses of the extract and fluoxetine compared to saline control. CONCLUSION: The extract of Papaver rhoeas can reduce immobility time which is comparable to the effect of fluoxetine. Also the effect of the extract is contrary to its effects on plasma corticosterone level and or animals' activity. PMID- 27563413 TI - Age-Related Differences in Neuropathic Pain Behavior and Spinal Microglial Activity after L5 Spinal Nerve Ligation in Male Rats. AB - INTRODUCTION: Several studies have reported the involvement of age-related changes in the development of neuropathic pain behaviors. However, limited data are available on the role of age in establishing and maintaining chronic neuropathic pain after peripheral nerve injury. METHODS: In the present study, we examined age-related neuropathic behavior among rats in 4 age groups: pups (4 weeks old; weight, 60-80 g), juvenile rats (6 weeks old; weight, 120-140 g), and mature rats (10-12 weeks old; weight, 200-250 g). Because the exact contribution of spinal microglia and its association with the development of neuropathic pain remains unknown, we also evaluated the expression of spinal Iba1, a microglial marker, by using western blotting before and 5 days after spinal nerve ligation (SNL) as well as after the daily IP administration of minocycline (30 mg/kg). RESULTS: Our results showed that SNL-induced mechanical allodynia but not thermal hyperalgesia in mature rats but not in pups (P<0.05 and P<0.01, respectively). The expression of spinal Iba1 in the juvenile rats was significantly lower than that in pups and mature rats (P<0.01). Moreover, administration of minocycline decreased the expression of spinal Iba1 in the pup rats more than in juvenile rats (P<0.001) and in the juvenile rats more than in the mature rats (P<0.05). CONCLUSION: These data suggest that the development of neuropathic behaviors and microglial activation after SNL could be age dependent. PMID- 27563414 TI - Effects of Dimethyl Sulfoxide on Neuronal Response Characteristics in Deep Layers of Rat Barrel Cortex. AB - INTRODUCTION: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for water-insoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200-1500 MUm depth) of the rat barrel cortex. METHODS: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. RESULTS: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. CONCLUSION: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex. PMID- 27563415 TI - Neural Correlates of Craving in Methamphetamine Abuse. AB - INTRODUCTION: Methamphetamine is a powerful psychostimulant that causes significant neurological impairments with long-lasting effects and has provoked serious international concerns about public health. Denial of drug abuse and drug craving are two important factors that make the diagnosis and treatment extremely challenging. Here, we present a novel and rapid noninvasive method with potential application for differentiation and monitoring methamphetamine abuse. METHODS: Visual stimuli comprised a series of images with neutral and methamphetamine related content. A total of 10 methamphetamine abusers and 10 age-gender matched controls participated in the experiments. Event-related potentials (ERPs) were recorded and compared using a time window analysis method. The ERPs were divided into 19 time windows of 100 ms with 50 ms overlaps. The area of positive sections below each window was calculated to measure the differences between the two groups. RESULTS: Significant differences between two groups were observed from 250 to 500 ms (P300) in response to methamphetamine-related visual stimuli and 600 to 800 ms in response to neutral stimuli. CONCLUSION: This study presented a novel and noninvasive method based on neural correlates to discriminate healthy individuals from methamphetamine drug abusers. This method can be employed in treatment and monitoring of the methamphetamine abuse. PMID- 27563416 TI - The Role of C Fibers in Spinal Microglia Induction and Possible Relation with TRPV3 Expression During Chronic Inflammatory Arthritis in Rats. AB - INTRODUCTION: Stimulation of peptidergic fibers activates microglia in the dorsal horn. Microglia activation causes fractalkine (FKN) release, a neuron-glia signal, which enhances pain. The transient vanilloid receptor 1 (TRPV1) mediates the release of neuropeptides, which can subsequently activate glia. TRPV1 and TRPV2 are generally expressed on C and Adelta fibers, respectively. Expression of both proteins is upregulated during inflammation, but expression of TRPV3 after induction of inflammation is unclear. METHODS: Adult male Wistar rats were used in all experiments. Arthritis was induced in them by single subcutaneous injection of complete Freund's adjuvant (CFA) in their right hindpaws. Resiniferatoxin (RTX) was used to eliminate peptidergic fibers. We examined the relation between FKN and TRPV3 expression by administration of anti-FKN antibody. RESULTS: Our study findings indicated that 1) spinal TRPV3 was mostly expressed on nonpeptidergic fibers, 2) expression of spinal TRPV3 increased following inflammation, 3) elimination of peptidergic fibers decreased spinal TRPV3 expression, 4) alteration of hyperalgesia was compatible with TRPV3 changes in RTX-treated rat, and 5) anti-FKN antibody reduced spinal TRPV3 expression. DISCUSSION: It seems that the hyperalgesia variation during different phases of CFA-induced arthritis correlates with spinal TRPV3 expression variation on peptidergic fibers. Moreover, spinal microglial activation during CFA inflammation is involved in TRPV3 expression changes via FKN signaling. PMID- 27563417 TI - Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex. AB - INTRODUCTION: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of MU-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at mRNA levels in rat striatum and prefrontal cortex (PFC) after induction of morphine tolerance. METHODS: Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1 gene expression was examined with a semi-quantitative RT-PCR method. RESULTS: The results showed that long-term morphine a administration induces tolerance to analgesic effect of the opioid, as revealed by a significant decrease in morphine induced analgesia on day 8 compared to day 1 of the injections (P<0.001). The results also showed that the NR1 gene expression at mRNA level in rats tolerant to morphine was significantly increased in the striatum (P<0.01) but decreased in the PFC (P<0.001). CONCLUSION: Therefore, changes in the NR1 gene expression in rat striatum and PFC have a region-specific association with morphine-induced analgesic tolerance. PMID- 27563418 TI - 5-HT2A Serotonin Receptor Density in Adult Male Rats' Hippocampus after Morphine based Conditioned Place Preference. AB - INTRODUCTION: A close interaction exists between the brain opioid and serotonin (5-HT) neurotransmitter systems. Brain neurotransmitter 5-HT plays an important role in the regulation of reward-related processing. However, a few studies have investigated the potential role of 5-HT2A receptors in this behavior. Therefore, the aim of the present study was to assess the influence of morphine and Conditioned Place Preference (CPP) on the density of 5-HT2A receptor in neurons of rat hippocampal formation. METHODS: Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1 gene expression was examined with a semi-quantitative RT PCR method. RESULTS: Our data showed that the maximum response was obtained with 2.5 mg/kg of morphine. The density of 5-HT2A receptor in different areas of the hippocampus increased significantly at sham-morphine and CPP groups (P<0.05). On the other hand, the CPP groups had more 5-HT2A receptors than sham-morphine groups and also the sham-morphine groups had more 5-HT2A receptors than the control groups. CONCLUSION: We concluded that the phenomenon of conditioned place preference induced by morphine can cause a significant increase in the number of serotonin 5-HT2A receptors in neurons of all areas of hippocampus. PMID- 27563420 TI - Repetitive Arm Movements During Sleep: A Polysomnographic Assessment. AB - Sleep-related movement disorders should be differentiated from parasomnias, sleep associated behavioral disorders, and epilepsy. Polysomnography (PSG) is the gold standard in evaluating such disorders. Periodic leg movement disorder during sleep (PLMS), hypnic jerks, bruxism, rhythmic movement disorder, restless legs syndrome, and nocturnal leg cramps have broadly been discussed in the literature. However, periodic arm movement disorder in sleep (PAMS) is a less-appreciated entity perhaps because arm surface electromyography is not an integral part of the standard polysomnography. Results from our PSG study in a case suspected for PAMS prompted us to herewith discuss this problem. PMID- 27563419 TI - The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats. AB - INTRODUCTION: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. METHODS: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. RESULTS: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). CONCLUSION: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID- 27563421 TI - Future Directions for Translation of Tissue Engineering Products into Clinic. PMID- 27563422 TI - Development of a Single Stranded DNA Aptamer as a Molecular Probe for LNCap Cells Using Cell-SELEX. AB - BACKGROUND: Nowadays, highly specific aptamers generated by cell SELEX technology (systematic evolution of ligands by exponential enrichment) are being applied for early detection of cancer cells. Prostate Specific Membrane Antigen (PSMA), over expressed in prostate cancer, is a highly specific marker and therefore can be used for diagnosis of the prostate cancer cells. The aim of the present study was to select single-stranded DNA aptamers against LNCap cells highly expressing PSMA, using cell-SELEX method which can be used as a diagnostic tool for the detection of prostate cancer cells. METHODS: After 10 rounds of cell-SELEX, DNA aptamers were isolated against PSMA using LNCaP cells as a target and PC-3 cell lines for counter SELEX. Five DNA aptamers with more than 70% affinity were selected up on flow cytometry analysis of positive clones. RESULTS: Dissociation constants of two selected sequences (A12-B1) were estimated in the range of 33.78+/-3.77 and 57.49+/-2.214 pmol, respectively. Conserved secondary structures of A12 and B1 sequences suggest the necessity of these structures for binding with high affinity to native PSMA. Comparison of the secondary structures of our isolated aptamers and aptamer A10 obtained by protein SELEX showed similar stem loop structures which could be responsible for the recognition of PSMA on LNCap cell surface. CONCLUSION: Our results indicated that selected aptamers may turn out to be ideal candidates for the development of a detection tool and also can be used in targeted drug delivery for future smart drugs. PMID- 27563423 TI - The Cytotoxicity of Dacarbazine Potentiated by Sea Cucumber Saponin in Resistant B16F10 Melanoma Cells through Apoptosis Induction. AB - BACKGROUND: Malignant melanoma is a highly aggressive malignant melanocytic neoplasm which resists against the most conventional therapies. Sea cucumber as one of marine organisms contains bioactive compounds such as polysaccharide, terpenoid and other metabolites which have anti-cancer, anti-tumor, anti inflammatory and antioxidant properties. The present study was designed to investigate the anticancer potential of saponin extracted from sea cucumber Holothuria leucospilata alone and in combination with dacarbazine on B16F10 melanoma cell line. METHODS: The B16F10 cell line was treated with different concentrations of saponin (0, 4, 8, 12, 16, 20 MUg/ml), dacarbazine (0, 1200, 1400, 1600, 18000, 1200, 1400, 1600, 2000 MUg/ml) and co-administration of saponin-dacarbazine (1200 da+8 sp, 1200 da+4 sp) for 24 and 48 hr and the cytotoxic effect was examined by MTT, DAPI, acridine orange/propodium iodide, flow cytometry and caspase colorimetric assay. RESULTS: The results exhibited that sea cucumber saponin, dacarbazine, and co-administration of saponin dacarbazine inhibited the proliferation of melanoma cells in a dose and time dependent manner with IC50 values of 10, 1400 and 4+1200 MUg/ml, respectively. Morphological observation of DAPI and acridine orange/propodium iodide staining documented typical characteristics of apoptotic cell death. Flow cytometry assay indicated accumulation of IC50 treated cells in sub-G1 peak. Additionally, saponin extracted induced intrinsic apoptosis via up-regulation of caspase-3 and caspase-9. CONCLUSION: These results revealed that the saponin extracted from sea cucumber as a natural anti-cancer compound may be a new treatment modality for metastatic melanoma and the application of sea cucumber saponin in combination with dacarbazine demonstrated the strongest anti-cancer activity as compared with the drug alone. PMID- 27563424 TI - Neuroprotective Effects of Herbal Extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on Rat Model of Sporadic Alzheimer's Disease. AB - BACKGROUND: Sporadic Alzheimer's Disease (SAD) is caused by genetic risk factors, aging and oxidative stresses. The herbal extract of Rosa canina (R. canina), Tanacetum vulgare (T. vulgare) and Urtica dioica (U. dioica) has a beneficial role in aging, as an anti-inflammatory and anti-oxidative agent. In this study, the neuroprotective effects of this herbal extract in the rat model of SAD was investigated. METHODS: The rats were divided into control, sham, model, herbal extract -treated and ethanol-treated groups. Drug interventions were started on the 21(st) day after modeling and each treatment group was given the drugs by intraperitoneal (I.P.) route for 21 days. The expression levels of the five important genes for pathogenesis of SAD including Syp, Psen1, Mapk3, Map2 and Tnf alpha were measured by qPCR between the hippocampi of SAD model which were treated by this herbal extract and control groups. The Morris Water Maze was adapted to test spatial learning and memory ability of the rats. RESULTS: Treatment of the rat model of SAD with herbal extract induced a significant change in expression of Syp (p=0.001) and Psen1 (p=0.029). In Morris Water Maze, significant changes in spatial learning seen in the rat model group were improved in herbal-treated group. CONCLUSION: This herbal extract could have anti-dementia properties and improve spatial learning and memory in SAD rat model. PMID- 27563425 TI - Inhibitory Effects of Some Carbohydrates on Nano-Globular Aggregation of both Normal and Glycated Albumin. AB - BACKGROUND: Protein aggregation is one of the important, common and troubling problems in biotechnology, pharmaceutical industries and amyloid-re-lated disorders. METHODS: In the present study, the inhibitory effects of some carbohydrates (alginate, beta-cyclodextrin and trehalose) on the formation of nano-globular aggregates from normal (HSA) and glycated (GHSA) human serum albumin were studied; when the formation of aggregates was induced by the simultaneous heating and addition of dithiotheritol. For the investigations, the biophysical methods of UV-vis spectrophotometry, circular dichroism spectroscopy, transmission electron microscopy and tensiometry were employed. RESULTS: The effect of inhibitory mechanism of these inhibitors on the aggregation of HSA and GHSA was expressed and compared together. CONCLUSION: The results showed that the nucleus formation step of the aggregation process of HSA and GHSA was different in the presence of alginate (compared to beta-cyclodextrin and trehalose). The inhibition efficiencies of the carbohydrates on the aggregate formation of HSA and GHSA were different, arising from the differences in the hydrophobicities of HSA and GHSA, and also, the differences between HSA- and GHSA-carbohydrate interactions. PMID- 27563426 TI - Effect of Removal of Spermatogonial Stem Cells (SSCs) from In Vitro Culture on Gene Expression of Niche Factors in Bovine. AB - BACKGROUND: Niche cells, regulating Spermatogonial Stem Cells (SSCs) fate are believed to have a reciprocal communication with SSCs. The present study was conducted to evaluate the effect of SSC elimination on the gene expression of Glial cell line-Derived Neurotrophic Factor (GDNF), Fibroblast Growth Factor 2 (FGF2) and Kit Ligand (KITLG), which are the main growth factors regulating SSCs development and secreted by niche cells, primarily Sertoli cells. METHODS: Following isolation, bovine testicular cells were cultured for 12 days on extracellular matrix-coated plates. In the germ cell-removed group, the SSCs were removed from the in vitro culture using differential plating; however, in the control group, no intervention in the culture was performed. Colony formation of SSCs was evaluated using an inverted microscope. The gene expression of growth factors and spermatogonia markers were assessed using quantitative real time PCR. RESULTS: SSCs colonies were developed in the control group but they were rarely observed in the germ cell-removed group; moreover, the expression of spermatogonia markers was detected in the control group while it was not observed in the germ cell-removed group, substantiating the success of SSCs removal. The expression of Gdnf and Fgf2 was greater in the germ cell-removed than control group (p<0.05), whereas the expression of Kitlg was lower in the germ cell removed than control group (p< 0.05). CONCLUSION: In conclusion, the results revealed that niche cells respond to SSCs removal by upregulation of GDNF and FGF2, and downregulation of KITLG in order to stimulate self-renewal and arrest differentiation. PMID- 27563427 TI - The Effect of Media Supplementation with Angiotensin on Developmental Competence of Ovine Embryos Derived from Vitrified-warmed Oocytes. AB - BACKGROUND: This study was aimed to assess the effects of angiotensin II (Ang II) supplementation to the In Vitro Maturation (IVM) and In Vitro Culture (IVC) media of vitrified-warmed ovine oocytes on their developmental competence and expression of Na(+)/K(+)/ATPase in resulting embryos. METHODS: The slaughterhouse derived immature oocytes (n=1069) were randomly distributed into four experimental groups: groups I and II) IVM/IVF and IVC of fresh and vitrified oocytes without angiotensin supplementation (Control-Fresh and Control-Vit groups, respectively); group III) IVM of vitrified oocytes in the presence of Ang II followed by IVF/IVC (Vit-IVM group); and group IV) IVM/IVF of vitrified oocytes followed by IVC wherein the embryos were exposed to Ang II on day 4 of IVC (Vit-D4 group). The embryos were immunostained with primary antibodies against Na(+)/K(+)/ATPase alpha1 and beta1 subunits. RESULTS: In Vit-IVM and Vit D4 groups, the rates of expanded and total blastocysts on day 7 as well as the proportion of blastocysts on day 8 were increased. The expression of Na(+)/K(+)/ATPase alpha1 and beta1 subunits were positively influenced by the addition of Ang II on day 4 (Vit-D4 group). CONCLUSION: The addition of Ang II to the IVM and IVC media could improve blastocysts formation in vitrified sheep oocytes. This improvement might be related to the greater expression of Na(+)/K(+)/ATPase alpha1 and beta1 subunits when Ang II was added during IVC. PMID- 27563428 TI - Leptin Receptor Gene Polymorphism may Affect Subclinical Atherosclerosis in Patients with Acromegaly. AB - BACKGROUND: Acromegaly is associated with increased morbidity and mortality related to cardiovascular diseases. Leptin (LEP) and Leptin Receptor (LEPR) gene polymorphisms can increase cardiovascular risks. The aim of this study was to investigate association between the frequencies of LEP and LEPR gene polymorphisms and subclinical atherosclerosis in acromegalic patients. METHODS: Forty-four acromegalic patients and 30 controls were admitted to study. The polymorphisms were identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose, fasting insulin, IGF-I, GH, IGFBP3, leptin, triglyceride, carotid Intima Media Thickness (cIMT) and HDL and LDL cholesterol concentrations were evaluated. RESULTS: There was statistically significant difference between the LEPR genotypes of acromegalic patients (GG 11.4%, GA 52.3%, and AA 36.4%) and controls (GG 33.3%, GA 50%, and AA 16.7%) although their LEP genotype distribution was similar. In addition, the prevalence of the LEPR gene G and A alleles was significantly different between patients and controls. No significant difference was found among the G(-2548) A leptin genotypes of groups in terms of the clinical parameters. cIMT significantly increased homozygote LEPR GG genotype group compared to AA subjects in patients. But the other parameters were not different between LEPR genotypes groups of patients and controls. CONCLUSION: It can be said that the LEPR gene polymorphism may affect cIMT in patients. The reason is that LEPR GG genotype carriers may have more risk than other genotypes in the development of subclinical atherosclerosis in acromegaly. PMID- 27563429 TI - Experiences of Cigarette Smoking among Iranian Educated Women: A Qualitative Study. AB - BACKGROUND: Smoking is a well-known public health problem in women as well as men. In many countries including Iran, there is an increase in tobacco use among women. Exploring the experience of smoking by educated women in order to develop effective tobacco prevention programs in these women is necessary. This study aimed to explore the experiences of smoking among Iranian educated women. METHODS: This study used a method of qualitative content analysis with the deep individual, semi-structured interviews on a sample of 14 educated female smokers, selected purposefully. Data were analyzed using qualitative content analysis with conventional approach while being collected. RESULTS: The data analysis led to 16 subcategories which were divided into four main categories: (1) Personal factors including subcategories of imitation, show-off and independence, inexperience and curiosity, personal interest and desire, improved mood, and social defiance; (2) family factors including smokers in the family, intrafamily conflicts, and family strictures and limitations; (3) social factors including subcategories of effects of work and school environment, gender equality symbols, peer pressure, and acceptance among friends; and (4) negative consequences of smoking including subcategories of a sense of being physically hurt, psychological and emotional stress, and being looked upon in a negative and judgmental manner. CONCLUSIONS: The findings of this study showed that smoking among Iranian educated women is a multifactorial problem. Thus, it is necessary to address smoking among educated women in a holistic approach that focuses on different determinants including personal, family, and social factors particularly the gender roles and stereotypes. PMID- 27563431 TI - Effect of Garlic and Lemon Juice Mixture on Lipid Profile and Some Cardiovascular Risk Factors in People 30-60 Years Old with Moderate Hyperlipidaemia: A Randomized Clinical Trial. AB - BACKGROUND: This study was performed to effects of garlic and lemon juice mixture on lipid profile and some cardiovascular risk factors in people 30-60 years old with moderate hyperlipidemia. METHODS: In a parallel-designed randomized controlled clinical trial, a total of 112 hyperlipidemic patients 30-60 years, were recruited from Isfahan Cardiovascular Research Center. People were selected and randomly divided into four groups. Control blood samples were taken and height, weight, and blood pressure were recorded. (1) Received 20 g of garlic daily, plus 1 tablespoon lemon juice, (2) received 20 g garlic daily, (3) received 1 tablespoon of lemon juice daily, and (4) did not receive garlic or lemon juice. A study technician was done the random allocations using a random numbers table. All participants presented 3 days of dietary records and 3 days of physical activity records during 8 weeks. Blood samples were obtained at study baseline and after 8 weeks of intervention. RESULTS: Results showed a significant decrease in total cholesterol (changes from baseline: 40.8 +/- 6.1, P < 0.001), low-density lipoprotein-cholesterol (29.8 +/- 2.6, P < 0.001), and fibrinogen (111.4 +/- 16.1, P < 0.001) in the Group 1, in comparison with other groups. A greater reduction in systolic and diastolic blood pressure was observed in Group 1 compared with the Groups 3 and 4 (37 +/- 10, P = 0.01) (24 +/- 1, P = 0.02); respectively. Furthermore, a great reduction in body mass index was observed in the mixed group compared with the lemon juice and control groups (1.6 +/- 0.1, P = 0.04). CONCLUSIONS: Administration of garlic plus lemon juice resulted in an improvement in lipid levels, fibrinogen and blood pressure of patients with hyperlipidemia. PMID- 27563430 TI - Effect of Tetanus-diphtheria Vaccine on Immune Response to Hepatitis B Vaccine in Low-responder Individuals. AB - BACKGROUND: Conventional hepatitis B virus (HBV) vaccination fails to achieve efficient protection in about 5-10% of the world population. Hence, different strategies have been adopted to ameliorate HBV antibody titers. This study aimed to evaluate the concurrent application of tetanus-diphtheria (Td) and HBV vaccination on hepatitis B surface (HBs) antibody titer in low-responder healthy individuals. METHODS: This was a randomized clinical trial, which was implemented among 140 of medical staff working as health-care workers assumed as low responders. The subjects were randomly allocated to either control or interventional groups. The control and interventional groups received HBV recombinant vaccine while the latter group was also vaccinated through Td. Enzyme linked immunosorbent assay was applied to measure HBs antibody (HBsAb) titers just before and 6 months after the last vaccination. All data were entered into SPSS software. Independent t-test, paired t-test, and Chi-square or Fisher's exact test were applied for data comparison. RESULTS: Antibody titers of the subjects in the intervention and control groups soared from 49.08 +/- 20.08 IU/L to 917.78 +/- 204.80 IU/L and from 46.95 +/- 18.55 to 586.81 +/- 351.77 IU/L, respectively (both P < 0.001); nevertheless, by comparison with control group, variation of antibody titer in the interventional group was significantly higher (P < 0.001). CONCLUSIONS: Concurrent application of Td and HBV vaccine could effectively enhance protective levels of HBsAb titers in low-responder individuals. PMID- 27563432 TI - Death Portrait of Isfahan Province in Years 2007-2011. AB - BACKGROUND: The rapid rise in noncommunicable diseases (NCDs) is one of the main health challenges affecting the global development in the present era. This raising challenge is a major threat to countries' socioeconomic development as well as millions of people health. METHODS: It was a retrospective study with analysis of reported death in Isfahan Province during a 5-year period from 2007 to 2011. Required data were collected from statistics provided by Deputy of Health in Kashan and Isfahan Universities of Medical Sciences in 2012. Excel software was used for data analysis. RESULTS: During this period, the cardiovascular events, cancers and tumors, unintentional injuries, respiratory diseases, and prenatal mortality were the main reasons of mortality in Isfahan Province. The overall rate of cardiovascular events rose 5.10% in the 5-years of the study observation, and Khor - Biabanak was on the top of the list; while in cancer rating Khor - Biabanak, Golpayegan, and Khansar both stood at the outset (per 1,000 people). For injuries, the highest rate belonged to Golpayegan, Tiran Kervan, and Chadegan. Meanwhile, for mental illnesses, the highest rate was observed in Khomeini Shahr. Moreover, the highest maternal and fetal mortality was reported in Fereydunshahr, Khor - Biabanak and Mobarakeh. CONCLUSIONS: Given the sharp rise of NCD, programs by health care system should be directed toward lifestyle modification while a proper framework should be determined to deal with these kinds of disease. Furthermore, optimal allocation of resources based on needs can provide better facilities for different cities. PMID- 27563433 TI - Anticonvulsant Effects of Lippia citriodora (Verbenaceae) Leaves Ethanolic Extract in Mice: Role of GABAergic System. AB - BACKGROUND: Lippia citriodora Kunth is one of the Iranian traditional medicines for the treatment of convulsive disorders. The goal of this study is to investigate the anticonvulsant activity of the plant's leave ethanolic extract against electro- and chemoconvulsant-induced seizures in mice. METHODS: The anticonvulsant activity of the extract (200, 400, 800 mg/kg, per os, p.o.) was investigated in pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures in mice. Diazepam (1 mg/kg) and phenytoin (25 mg/kg) intraperitoneally (i.p.) were used as reference drugs. In addition, for investigating the role of GABAergic system, flumazenil (2 mg/kg, i.p.) was also injected before L. citriodora. RESULTS: The extract had not any toxicity and significantly decreased the duration and increased the latency of the seizures induced by PTZ (90 mg/kg). In the MES test, L. citriodora displayed statistically significant reduction in hind limb tonic extension duration in a nondose-dependent manner. Flumazenil reversed the anticonvulsant activity of the plant's extract in the PTZ model. CONCLUSIONS: The results propose that L. citriodora leave ethanolic extract has anticonvulsant activity against convulsive disorders. It seems that this plant's extract generates its antiseizure effect through GABAergic system potentiation. Further studies will be needed in order to investigate the exact mechanisms of it. Moreover, one may conclude that the present results are in accordance with the positive effect of L. citriodora extract to treat convulsion mentioned in old Iranian literature. PMID- 27512559 TI - Terminal investment induced by a bacteriophage in a rhizosphere bacterium. AB - Despite knowledge about microbial responses to abiotic stress, few studies have investigated stress responses to antagonistic species, such as competitors, predators and pathogens. While it is often assumed that interacting populations of bacteria and phage will coevolve resistance and exploitation strategies, an alternative is that individual bacteria tolerate or evade phage predation through inducible responses to phage presence. Using the microbial model Pseudomonas fluorescens SBW25 and its lytic DNA phage SBW25Phi2, we demonstrate the existence of an inducible response in the form of a transient increase in population growth rate, and found that the response was induced by phage binding. This response was accompanied by a decrease in bacterial cell size, which we propose to be an associated cost. We discuss these results in the context of bacterial ecology and phage-bacteria co-evolution. PMID- 27563435 TI - Erratum to: Use of near-infrared reflectance spectroscopy for the rapid determination of the digestible energy and metabolizable energy content of corn fed to growing pigs. AB - [This corrects the article DOI: 10.1186/s40104-016-0105-9.]. PMID- 27563436 TI - Modulating In Vivo Degradation Rate of Injectable Extracellular Matrix Hydrogels. AB - Extracellular matrix (ECM) derived hydrogels are increasingly used as scaffolds to stimulate endogenous repair. However, few studies have examined how altering the degradation rates of these materials affect cellular interaction in vivo. This study sought to examine how crosslinking or matrix metalloproteinase (MMP) inhibition by doxycycline could be employed to modulate the degradation rate of an injectable hydrogel derived from decellularized porcine ventricular myocardium. While both approaches were effective in reducing degradation in vitro, only doxycycline significantly prolonged hydrogel degradation in vivo without affecting material biocompatibility. In addition, unlike crosslinking, incorporation of doxycycline into the hydrogel did not affect mechanical properties. Lastly, the results of this study highlighted the need for development of novel crosslinkers for in situ modification of injectable ECM derived hydrogels, as none of the crosslinking agents investigated in this study were both biocompatible and effective. PMID- 27563437 TI - Initiating therapeutic relaxation in Britain: a twentieth-century strategy for health and wellbeing. AB - In 1972, a British charity, Relaxation for Living, was established "to promote the teaching of physical relaxation, to combat stress, strain, anxiety and the tension of modern life, and to reduce fatigue". This article explores the origins and development of "physical relaxation" techniques and ideologies, starting in the interwar period, and the development of practical, therapeutic, social and cultural frameworks necessary for such an organization to come into being in 1970s Britain. It traces how relaxation was reconstituted as a scientifically based skill that could be learnt and taught, imbued with therapeutic value for combating and preventing specific physical ailments and enhancing individual health and wellbeing. The article explores how relaxation techniques gained currency among particular demographic and clinical groups, ranging from middle class, child-bearing women to middle-aged, "coronary-prone" men. This analysis highlights the role that relaxation practitioners played in both creating and responding to demand for individualistic health-management strategies, many of which have shaped contemporary health and wellbeing agendas. This article is published as part of a collection entitled "On balance: lifestyle, mental health and wellbeing". PMID- 27563438 TI - Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience. AB - BACKGROUND: Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity. METHODS: HER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression. RESULTS: Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01-5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5-53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population. CONCLUSIONS: In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted. PMID- 27563439 TI - Use of positron emission tomography scan response to guide treatment change for locally advanced gastric cancer: the Memorial Sloan Kettering Cancer Center experience. AB - BACKGROUND: Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non responders. METHODS: Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m(2), cisplatin 60 mg/m(2) day 1, and capecitabine 625 mg/m(2) bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., >=35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m(2), irinotecan 50 mg/mg(2) day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders. RESULTS: Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30-85%] in responders compared with 56% in the non responder group (95% CI, 20-80%, P=0.93). CONCLUSIONS: The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial. PMID- 27563440 TI - Esophagojejunal anastomosis leakage after total gastrectomy for esophagogastric junction adenocarcinoma: options of treatment. AB - BACKGROUND: Esophagojejunal anastomosis leakage after total gastrectomy (TG) for esophagogastric junction (EGJ) adenocarcinoma (ADC) constitutes one of the most serious and sometimes life-threatening complications. Management remains controversial and still challenging. METHODS: A total of 198 patients operated for type I and II EGJ ADC were reviewed. Diagnosis of leakage was based on a combination of clinical and radiological findings. It was classified including objective endoscopic and clinical parameters requiring different type of treatment. RESULTS: Anastomotic leakage was diagnosed in 14 patients (7%). Two cases recovered with conservative therapy. Six cases underwent endoscopy with clips placement in 2 and partially covered self-expandable metal stent placement in 4. Other two cases underwent reoperation with reconstruction of anastomosis and primary repair respectively. In the last four cases emergency surgery with total esophagectomy and diversion was required. Mortality occurred only in 3 of these patients and overall treatment was successful in 11 patients (78.5%). CONCLUSIONS: No consensus has been reached on the best method of esophagojejunal anastomosis leakage management and the rate of failure remains significant. Different options of treatment are available but early detection and multidisciplinary approaches are the keys to obtain successful results irrespective of the employed strategy. PMID- 27563441 TI - Hyperthermic intraperitoneal chemotherapy (HIPEC) and neoadjuvant chemotherapy as prophylaxis of peritoneal carcinosis from advanced gastric cancer-effects on overall and disease free survival. AB - BACKGROUND: The possibility to enlarge criteria for intra-peritoneal chemotherapy (IPC) to all patients at high-risk to develop peritoneal carcinosis (i.e., with serosal invasion) is still discussed. METHODS: Retrospective case-control study. Three-groups: advanced-gastric-cancer (AGC) (pT4) without proven carcinosis: prophylactic group (PG), those with PC: treatment group (TG), AGC (pT3-pT4) operated without hyperthermic intraperitoneal chemotherapy (HIPEC), surgery alone group (SG T3, SG T4). RESULTS: Forty four patients. 26 (59.1%) were male. Sixteen (36%) patients underwent 16 HIPEC: 6 (38%) had AGC (pT4) without PC (PG), 10 (62%) had carcinosis (TG), 28 were operated without HIPEC (SG T3, SG T4). The mean disease free survival (DFS): TG: 7.7 months, SG T4: 21.6 months, SG T3: 27.7 months, PG: 34.5 months. DFS was significantly different for TG (P=0.03, P=0.021, P=0.013 respectively). The mean OS TG: 10 months, SG T4: 27.1 months, SG T3: 28.2 months, PG: 34.6 months. OS was significantly different for TG (P=0.04, P=0.04, P=0.045 respectively). Severe complication rate: TG: 60%, PG: 16.7%, SG T3: 7.7% and SG T4: 25% (P=0.035). Length-of-stay differs significantly (P=0.003); overall length-of-stay: 19.41 days [standard deviation (SD) +/-15.03]; TG: 33.01 (SD +/ 23.08), PG: 20.17 (SD +/-6.21), SG T3: 11.33 (SD +/-3.22), SG T4: 15.36 (SD +/ 5.48). CONCLUSIONS: Prophylactic intraperitoneal chemotherapy associated to neoadjuvant chemotherapy increases the DFS and OS in patients with AGC without carcinosis. More data are needed in order to confirm these results. PMID- 27563442 TI - Administered activity and outcomes of glass versus resin (90)Y microsphere radioembolization in patients with colorectal liver metastases. AB - BACKGROUND: Given the differences in size, specific activity, and dosing methods for glass yttrium-90 microspheres ((90)Y-glass) and resin (90)Y microspheres ((90)Y-resin), these therapies may expose the liver to different amounts of radiation, thereby affecting their efficacy and tolerability. We aimed to compare the prescribed activity of (90)Y-glass and (90)Y-resin for real-world patients undergoing selective internal radiation therapy (SIRT) for liver-dominant metastatic colorectal cancer (mCRC) and to assess efficacy and safety outcomes in these patients. METHODS: We examined the records of 28 consecutive patients with unresectable colorectal liver metastases treated with SIRT between June 2008 and May 2011 at our institution. Using baseline CT and MR images, we calculated a projected activity as if we had used the other product and compared it to the actual prescribed activity of (90)Y-glass and (90)Y-resin for each SIRT treatment per manufacturer guidelines. Progression and adverse events were evaluated at follow up visits. Survival was analyzed by the Kaplan-Meier method. RESULTS: For (90)Y-glass treatments with a mean prescribed (90)Y activity of 1.77 GBq, the mean projected (90)Y-resin activity was 0.84 GBq. For (90)Y-resin treatments with a mean prescribed (90)Y activity of 1.05 GBq, the mean projected (90)Y-glass activity was 2.48 GBq. The median survival was 9.3 months versus 18.2 months for (90)Y-glass and (90)Y-resin, respectively (P=0.292). During the second year after SIRT, the hazard ratio of death for patients treated with (90)Y-glass versus (90)Y-resin was 4.0 (95% CI: 1.3, 12.3; P=0.017). No significant difference in progression, adverse events or liver toxicity was observed. CONCLUSIONS: Using manufacturer recommended guidelines, (90)Y-resin delivers significantly less activity than (90)Y-glass to patients with liver-dominant mCRC undergoing SIRT with no significant difference in adverse events and a trend toward improved survival. PMID- 27563443 TI - Clinical outcomes of pancreaticoduodenectomy in octogenarians: a surgeon's experience from 2007 to 2015. AB - BACKGROUND: As the number of elderly people in our population increases, there will be a greater number of octogenarians who will need pancreaticoduodenectomy as the only curative option for periampullary malignancies. This study evaluated clinical outcomes of pancreaticoduodenectomy in octogenarians, in comparison to younger patients. METHODS: A retrospective review was conducted of 216 consecutive patients who underwent pancreaticoduodenectomy from January 2007 to April 2015. A two-sided Fisher's exact statistical analysis was used to compare pre-operative comorbidities, intra-operative factors, surgical pathology, and post-operative complication rates between non-octogenarians and octogenarians. RESULTS: One hundred and eighty three non-octogenarians and 33 octogenarians underwent pancreaticoduodenectomy. Of patients with periampullary adenocarcinoma, octogenarians were more likely to present with advanced disease state (P=0.01). The two cohorts had similar ASA scores (P=0.62); however, octogenarians were more likely to have coronary artery disease (P=0.03). The length of operation was shorter in octogenarians (P=0.002). Mortality rates (P=0.49) and overall postoperative complication rates (P=1.0) were similar in two cohorts; however octogenarians had a higher incidence of pulmonary embolism (P=0.02). CONCLUSIONS: Our data demonstrates that octogenarians can undergo pancreaticoduodenectomy with outcomes similar to those in younger patients. Thus, patients should not be denied a curative surgical option for periampullary malignancy based on advanced age alone. PMID- 27563444 TI - Favorable perioperative outcomes after resection of borderline resectable pancreatic cancer treated with neoadjuvant stereotactic radiation and chemotherapy compared with upfront pancreatectomy for resectable cancer. AB - BACKGROUND: Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) are utilized to increase margin negative (R0) resection rates in borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) patients. Concerns persist that these neoadjuvant therapies may worsen perioperative morbidities and mortality. METHODS: Upfront resection patients (n=241) underwent resection without neoadjuvant treatment for resectable disease. They were compared to BRPC or LAPC patients (n=61) who underwent resection after chemotherapy and 5 fraction SBRT. Group comparisons were performed by Mann-Whitney U or Fisher's exact test. Overall Survival (OS) was estimated by Kaplan-Meier and compared by log-rank methods. RESULTS: In the neoadjuvant therapy group, there was significantly higher T classification, N classification, and vascular resection/repair rate. Surgical positive margin rate was lower after neoadjuvant therapy (3.3% vs. 16.2%, P=0.006). Post-operative morbidities (39.3% vs. 31.1%, P=0.226) and 90-day mortality (2% vs. 4%, P=0.693) were similar between the groups. Median OS was 33.5 months in the neoadjuvant therapy group compared to 23.1 months in upfront resection patients who received adjuvant treatment (P=0.057). CONCLUSIONS: Patients with BRPC or LAPC and sufficient response to neoadjuvant multi-agent chemotherapy and SBRT have similar or improved peri-operative and long-term survival outcomes compared to upfront resection patients. PMID- 27563445 TI - BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype. AB - BACKGROUND: BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. METHODS: The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. RESULTS: Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. CONCLUSIONS: BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1 targeted therapies need to be investigated. PMID- 27563446 TI - Outcomes in patients with brain metastasis from esophageal carcinoma. AB - BACKGROUND: Brain metastases from esophageal carcinoma have historically been rare and associated with poor prognosis. With improvements in systemic disease control, the incidence of brain metastases is expected to rise. To better inform management decisions, we sought to identify factors associated with survival in patients with brain metastasis from esophageal cancer. METHODS: We retrospectively identified 49 patients with brain metastasis from stage I-IV primary esophageal cancer treated with surgery, radiation, or a combination of modalities at our tertiary referral center between 1998 and 2015. Medical records were reviewed to collect demographic and clinical information. RESULTS: Median age at diagnosis of the primary esophageal cancer was 60 years. Forty-one (84%) patients were male and forty patients (82%) had adenocarcinoma. Median overall survival (MS) following esophageal cancer diagnosis was 24 months (range, 3-71 months), and median survival after the identification of brain metastases was 5 months (range, 1-52 months). On univariate analysis, only patients with poor Karnofsky performance status (KPS <70), recursive partitioning analysis (RPA) classification (III), or 3 or more brain metastases were found to have worsened survival after the diagnosis of brain metastases (all P<0.01). Factors not associated with survival were age, gender, histology (adenocarcinoma vs. other), palliative-intent treatment of the primary tumor, time to diagnosis of brain metastases from initial diagnosis, uncontrolled primary tumor at time of brain metastasis diagnosis, or extracranial metastases. On multivariate analysis (MVA, KPS excluded), patients with RPA class I (MS, 14.6 months) or II (MS, 5.0 months) disease had significantly improved overall survival compared to class III disease (MS, 1.6 months, P<0.01). Also on MVA, patients with 1 (MS, 10.7 months) or 2 (MS, 4.7 months) brain metastases had significantly improved overall survival compared to patients with 3 or more brain metastases (MS, 0.3 months, P<0.01). For the 36 patients with 1-2 brain metastases and KPS >=70, MS was 11.1 months. CONCLUSIONS: While the prognosis for esophageal cancer metastatic to brain remains poor overall, we found that patients with good performance status and limited number of brain lesions have superior survival. Aggressive management may further improve outcomes in these patients. PMID- 27563447 TI - A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma. AB - BACKGROUND: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database. METHODS: To evaluate the genetic associations with each variable we utilized GeneCards((r)), The Human Gene Compendium (http://www.genecards.org). The results of our search were entered into the Pathway Interaction Database from the National Cancer Institute (PID-NCI) (http://pid.nci.nih.gov), to generate a biomolecule interaction map. RESULTS: The results of our query yielded 690 genes for HCC, 98 genes for CC and 50 genes for HCC-CC. Genes depicted in this analysis demonstrate the role of hormonal regulation, embryonic development, cell surface adhesion, cytokeratin stability, mucin production, metalloproteinase regulation, Ras signaling, metabolism and apoptosis. Examples of previously described markers included hepatocyte growth factor (HGF), mesenchymal epithelial transition (MET) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Novel markers included phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), GPC3, choline kinase alpha (CHKA), prostaglandin-endoperoxide synthase 2 (PTGS2), telomerase reverse transcriptase (TERT), myeloid cell leukemia 1 (MCL1) and N acetyltransferase 2 (NAT2). CONCLUSIONS: GeneCards is a useful research tool in the genetic analysis of low frequency malignancies. Utilizing this tool we identified several biomarkers are methods for diagnosing HCC-CC. Finally, utilizing these methods, HCC-CC was found to be predominantly a subtype of CC. PMID- 27563448 TI - Comparison of external beam radiation and brachytherapy to external beam radiation alone for unresectable extrahepatic cholangiocarcinoma. AB - BACKGROUND: Extrahepatic cholangiocarcinoma (EHC) is a rare malignancy with a relatively poor prognosis. There are no randomized, prospective data to help define the optimal method of radiation delivery for unresectable EHC. The purpose of this study was to evaluate the benefit of adding brachytherapy to external beam radiation therapy (EBRT) for unresectable EHC. METHODS: A retrospective review of 1,326 patients with unresectable EHC using the Surveillance, Epidemiology, and End Results (SEER) database was completed. Kaplan-Meier methods were used to analyze the primary endpoint, overall survival. Univariate and multivariate analysis was performed to identify and control for potential confounding variables, including age at diagnosis, sex, stage, grade, histology, race, year of diagnosis, and reason for no surgery. RESULTS: Of the 1,326 patients with unresectable EHC, 1,188 (92.9%) received EBRT only, while 91 (7.1%) received both EBRT and brachytherapy. Patients receiving combined modality radiation therapy were more likely to be treated prior to the year 2000. Median overall survival for patients receiving EBRT and EBRT plus brachytherapy was 9 and 11 months, respectively (P=0.04). Cause specific survival was 12 months for those receiving EBRT only, and 15 months for those who received EBRT + brachytherapy (P=0.10). Survival analysis performed on patients with locoregional disease only revealed a trend towards prolonged overall survival with those receiving EBRT + brachytherapy (P=0.08). Multivariate analysis revealed grade and stage of disease were correlated with both overall survival and cause specific survival (P<=0.05). CONCLUSIONS: Among patients with unresectable EHC, the addition of brachytherapy to EBRT is associated with a prolonged median overall survival. However, the use of brachytherapy boost decreased in the last decade of the study. PMID- 27563449 TI - Nab-paclitaxel as alternative treatment regimen in advanced cholangiocellular carcinoma. AB - BACKGROUND: Advanced cholangiocellular carcinoma has a poor prognosis with limited therapeutic options. Nab-paclitaxel has recently been described to be beneficial in metastatic pancreatic cancer improving overall and progression free survival (PFS). The potential antitumor activity of nab-paclitaxel in cholangiocellular carcinoma is hitherto unknown. METHODS: We retrospectively analyzed an institutional cholangiocellular carcinoma registry to determine the potential biological activity of nab-paclitaxel in advanced intrahepatic cholangiocellular carcinoma. Disease control rate (DCR), PFS and overall survival (OS) upon nab-paclitaxel based treatment, after failure of platinum-containing first-line combination chemotherapy, was assessed. RESULTS: Twelve patients were identified. Five of 12 patients (42%) received nab-paclitaxel as second line, and 7 patients (56%) as third-line treatment. The objective DCR with nab-paclitaxel was 83% (10/12 patients). One patient had a complete remission (CR), two patients had a partial remission (PR) and 7 patients had stable disease (SD). Disease was rated progressive in two patients. In all 12 patients receiving nab-paclitaxel the median time to progression was 6 months (range, 2.1-19.5 months). Median OS after initiation of nab-paclitaxel treatment was 9 months (2.1-28.4 months). The median time of survival after diagnosis of advanced disease was 21.5 months, whereby 3 patients were alive at the date of censoring (04/01/2015). CONCLUSIONS: This is the first report suggesting substantial antitumor activity of nab paclitaxel in advanced cholangiocellular carcinoma. In this small series, nab paclitaxel based salvage chemotherapy appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this disease entity and subgroup of patients are urged. PMID- 27563451 TI - Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome. AB - BACKGROUND: Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. METHODS: A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. RESULTS: 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4-9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. CONCLUSIONS: The majority of patients showed some response to neoadjuvant treatment. Findings of this study indicate tumour response to neoadjuvant CRT improves the long-term outcome, with a better result in patients with pCR. PMID- 27563450 TI - Comparative effectiveness of chemopreventive interventions for colorectal cancer: protocol for a systematic review and network meta-analysis of randomised controlled trials. AB - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with substantial socioeconomic burden. Despite considerable research, including numerous randomised controlled trials (RCTs) and systematic reviews assessed the effect of various chemopreventive interventions for CRC, there remains uncertainty regarding the comparative effectiveness of these agents. No network meta-analytic study has been published to evaluate the efficacies of these agents for CRC. Therefore, the aim of this study is to summarise the direct and indirect evidence for these interventions to prevent CRC in average-high risk individuals, and to rank these agents for practical consideration. METHODS: We will acquire eligible studies through a systematic search of MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, CINAHL plus, IPA and clinicaltrials.gov website. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are the incidence of CRC, the incidence/recurrence of any adenoma or change in polyp burden (number or size). Quantitative synthesis or meta-analysis will be considered. We will also construct a network meta-analysis (NMA) to improve precision of the comparisons among chemo-preventive interventions by combining direct and indirect evidence. The probability of each treatment being the best and/or safest, the number-needed-to-treat [NNT; 95% credible interval (CrIs)], and the number-needed-to-harm (NNH; 95% CrIs) will be calculated to provide measures of treatment efficacy. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA. RESULTS: This protocol has been registered (registration number: CRD42015025849) with the PROSPERO (International Prospective Register of Systematic Reviews). The procedures of this systematic review and NMA will be conducted in accordance with the PRISMA compliant guideline. The results of this systematic review and NMA will be submitted to a peer-reviewed journal for publication. CONCLUSIONS: To the best of our knowledge, this study will be the first NMA to identify the comparative effectiveness of interventions for the prevention of CRC. The results of our study will update evidence for chemoprevention of CRC, identify key areas for future research, and provide a framework for conducting large systematic reviews involving indirect comparisons. PMID- 27563452 TI - Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas. AB - BACKGROUND: Limited knowledge exists about the effects chronic hepatitis C virus (HCV) infection has in the development of colorectal adenomas (CRA). Data regarding the association between chronic HIV infection and the development of CRA is scarce as well. We aim to determine if there is an association between the development of CRA and chronic infection with HCV and HCV/HIV co-infection. METHODS: From July 1, 2009 to March 31, 2011 a total of 2,051 patients that underwent colonoscopy were included in our study. The population was divided into 2 study groups: those patients who tested positive for HCV, and HCV/HIC; the control groups consisted of patients whose results were negative. Fisher's exact chi(2) test for categorical variables and t-test for continuous variables was used to analyze data between groups. Logistic regression was performed to obtain odds ratios (OR). RESULTS: CRA detection was higher in the HCV than in the control group (26.3% vs. 20.2%; P=1.02); Likewise, the incidence of CRA (25.5% vs. 20.8%; P=0.63) was higher in the co-infection group. However, in both of the study groups this difference was non-statistical. CONCLUSIONS: A higher detection rate of CRP was seen in the HCV population; however, it failed to reach statistical significance. Whether co-infection with HIV/HCV increases the incidence of CRA and/or has a synergistic effect remains to be determined. The small sample population and the retrospective single institution nature of our study, as well as other confounders may have contributed to our negative results. However, our findings question whether HCV and HIV/HCV co-infected patients will benefit from screening colonoscopy at an earlier age. This issue merits further investigation with a large multi-center prospective study. PMID- 27563453 TI - The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis. AB - BACKGROUND: Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis. METHODS: Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment. RESULTS: Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH. CONCLUSIONS: We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy. PMID- 27563454 TI - Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib. AB - BACKGROUND: Multimodality treatment of gastrointestinal stromal tumor (GIST) with surgery and adjuvant imatinib mesylate (IM), along with an emerging role for neoadjuvant IM prior to evaluation for resectability has resulted in high survival rates. METHODS: We conducted a retrospective analysis of prospectively collected data of patients who underwent surgery for GIST, prior to or followed by IM therapy. A total of 112 patients underwent surgery between January 2009 and March 2015 at our centre. This included 27 patients with upfront resectable disease, 76 patients with locally advanced GIST who received neoadjuvant IM followed by surgery and 9 patients with metastatic disease who had excellent response to IM and were taken for surgery. RESULTS: The primary tumor in the non metastatic patients was in the stomach (53%), duodenum (16%), rectum (12%), jejunum (11%), ileum (7%), and others (2%). Median duration of neoadjuvant IM was 5 months with 4 patients showing disease progression during neoadjuvant IM. Ninety-three percent of all patients had R0 resections, while 7% had R+ resections. The estimated 3- and 5-year DFS in non-metastatic patients was 86.1% and 67% respectively with a 3- and 5-year median OS of 95.4% and 91.7% respectively. Five-year PFS and OS for the metastatic patients was 88.8% and 100% respectively. Lack of adjuvant IM was the only factor related to inferior PFS and OS. CONCLUSIONS: Longer duration of neoadjuvant IM should be considered in locally advanced GIST prior to surgery and resection may be considered in responding metastatic patients. PMID- 27563455 TI - Treatment of non-resectable and metastatic gastrointestinal stromal tumors: experience with the use of tyrosine kinase inhibitors in a third level hospital in Mexico. AB - BACKGROUND: Stromal tumors of the digestive tract are uncommon malignant diseases, are subclassified as leiomyosarcomas and Gastrointestinal Stromal Tumors (GIST) depending on the molecular expression of tyrosine kinase receptor KIT (CD117). GISTs represent 1% of malignant tumors affecting this anatomical site. Localized tumours diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since tyrosine kinase inhibitors (TKIs) were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. METHODS: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. RESULTS: We obtained information of 71 patients with metastatic, non-resectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%) with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%), most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 30.6 months and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400 mg per day. Treatment was well-tolerated in most cases. CONCLUSIONS: Metastatic GIST evaluated in our center shows a different affection in gender and age, and our population shows a different response to TKIs, compared to those reported in other series with superior overall survival. Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors. PMID- 27563456 TI - Pazopanib in metastatic multiply treated progressive gastrointestinal stromal tumors: feasible and efficacious. AB - BACKGROUND: A median progression free survival (PFS) of 18-20 months and median overall survival (OS) of 51-57 months can be achieved with the use of imatinib, in metastatic or advanced gastrointestinal stromal tumor (GIST). Sunitinib and regorafenib are approved options for patients progressing on imatinib, but with markedly decreased survival. pazopanib is a broad spectrum TKI targeting KIT, PDGFR and VEGFR receptors and has shown promising activity in phase 2 trials in GIST. METHODS: All patients who received pazopanib for GIST between March 2014 and September 2015 in our institution were reviewed. Patients were assessed for response with CT or PET CT scans. Patients continued pazopanib until progression or unacceptable toxicity. Survival was evaluated by Kaplan Meier product method. RESULTS: A total of 11 consecutive patients were included in our study. Median duration of follow up was seven months. The median lines of prior therapy was 2 [1-5]. Partial response (PR) was observed in seven patients and two had stable disease (SD). Two patients died within one month of start of pazopanib. Five of ten patients had progressed during the study with eight patients still alive. The median PFS was 11.9 months and the median OS was not reached. Common adverse events seen were hand-foot-syndrome (HFS) in four patients, anemia in four patients and fatigue in three patients. Grade 3/4 adverse events were uncommon. Three patients required dose modification of pazopanib. CONCLUSIONS: Pazopanib is a reasonably efficacious well tolerated TKI and can be explored as a treatment option in advanced GIST that has progressed on imatinib. PMID- 27563457 TI - Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review. AB - BACKGROUND: Proton beam radiotherapy (PBT) is frequently shown to be dosimetrically superior to photon radiotherapy (RT), though supporting data for clinical benefit are severely limited. Because of the potential for toxicity reduction in gastrointestinal (GI) malignancies, we systematically reviewed the literature on clinical outcomes (survival/toxicity) of PBT. METHODS: A systematic search of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology was conducted for publications from 2000-2015. Thirty-eight original investigations were analyzed. RESULTS: Although results of PBT are not directly comparable to historical data, outcomes roughly mirror previous data, generally with reduced toxicities for PBT in some neoplasms. For esophageal cancer, PBT is associated with reduced toxicities, postoperative complications, and hospital stay as compared to photon radiation, while achieving comparable local control (LC) and overall survival (OS). In pancreatic cancer, numerical survival for resected/unresected cases is also similar to existing photon data, whereas grade >=3 nausea/emesis and post-operative complications are numerically lower than those reported with photon RT. The strongest data in support of PBT for HCC comes from phase II trials demonstrating very low toxicities, and a phase III trial of PBT versus transarterial chemoembolization demonstrating trends towards improved LC and progression-free survival (PFS) with PBT, along with fewer post-treatment hospitalizations. Survival and toxicity data for cholangiocarcinoma, liver metastases, and retroperitoneal sarcoma are also roughly equivalent to historical photon controls. There are two small reports for gastric cancer and three for anorectal cancer; these are not addressed further. CONCLUSIONS: Limited quality (and quantity) of data hamper direct comparisons and conclusions. However, the available data, despite the inherent caveats and limitations, suggest that PBT offers the potential to achieve significant reduction in treatment-related toxicities without compromising survival or LC for multiple GI malignancies. Several randomized comparative trials are underway that will provide more definitive answers. PMID- 27563458 TI - A comparison between 5-fluorouracil/mitomycin and capecitabine/mitomycin in combination with radiation for anal cancer. AB - BACKGROUND: There are no randomized phase III trials comparing 5 fluorouracil/mitomycin (FM) versus capecitabine/mitomycin (CM) in combination with radiotherapy (RT) for locally advanced anal cancer. We aim to evaluate the outcomes of patients treated with FM and CM at our institution. METHODS: Patients with stage I-III anal cancer who initiated curative-intent RT (50-54 Gy) with either CM or FM between 1998 and 2013 at the BC Cancer Agency were reviewed. Cox proportional models were used to analyze the impact of regimen on disease-free survival (DFS) and anal cancer-specific survival (ACSS). RESULTS: A total of 300 patients were included. Baseline characteristics were well-distributed between the groups. A total of 194 patients (64.6%) received FM and 106 (35.3%) CM. The 2 year DFS was 79.7% for CM [95% confidence intervals (95% CI), 71.1-88.3%] and 78.8% for FM (95% CI, 73-84.6%); 2-year ACSS was 88.7% for CM (95% CI, 81.8 95.5%) and 87.5% for FM (95% CI, 82.8-92.2%). On multivariate analysis, only HIV status, clinical T size (<=5 vs. >5 cm), and N status (negative vs. positive) remained as significant prognostic factors for both DFS and ACSS. Chemotherapy regimen (CM vs. FM) had no impact on either DFS [P=0.995; hazard ratios (HR) =0.99; 95% CI, 0.57-1.74] or ACSS (P=0.847; HR =0.93; 95% CI, 0.46-1.86). CONCLUSIONS: In our population-based study, CM and FM concomitant with RT achieved similar DFS and ACSS. Substitution of capecitabine for infusional 5-FU may therefore be a reasonable option for patients and physicians who prefer to avoid the inconvenience and potential complications of a central infusional device. PMID- 27563459 TI - Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans. AB - Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD. PMID- 27563460 TI - Visual Performance after Bilateral Implantation of a Four-Haptic Diffractive Toric Multifocal Intraocular Lens in High Myopes. AB - Background. The vision with diffractive toric multifocal intraocular lenses after cataract surgery in long eyes has not been studied previously. Objectives. To report visual performance after bilateral implantation of a diffractive toric multifocal intraocular lens in high myopes. Methods. Prospective, observational case series to include patients with axial length of >=26 mm and corneal astigmatism of >1 dioptre who underwent bilateral AT LISA 909M implantation. Postoperative examinations included photopic and mesopic distance, intermediate, and near visual acuity; photopic contrast sensitivity; visual symptoms (0-5); satisfaction (1-5); and spectacle independence rate. Results. Twenty-eight eyes (14 patients) were included. Postoperatively, mean photopic monocular uncorrected distance, intermediate, and near visual acuities (logMAR) were 0.12 +/- 0.20 (standard deviation), 0.24 +/- 0.16, and 0.29 +/- 0.21, respectively. Corresponding binocular values were -0.01 +/- 0.14, 0.13 +/- 0.12, and 0.20 +/- 0.19, respectively. One eye (4%) had one-line loss in vision. Under mesopic condition, intermediate vision and near vision decreased significantly (all P <= 0.001). Contrast sensitivity at all spatial frequencies did not improve significantly under binocular condition (all P > 0.05). Median scores for halos, night glare, starbursts, and satisfaction were 0.50, 0.00, 0.00, and 4.25, respectively. Ten patients (71%) reported complete spectacle independence. Conclusions. Bilateral implantation of the intraocular lens in high myopes appeared to be safe and achieved good visual performance and high satisfaction. PMID- 27563461 TI - An eco-friendly method of synthesizing gold nanoparticles using an otherwise worthless weed pistia (Pistia stratiotes L.). AB - A biomimetic method of gold nanoparticles synthesis utilizing the highly invasive aquatic weed pistia (Pistia stratiotes) is presented. In an attempt to utilize the entire plant, the efficacy of the extracts of all its parts - aerial and submerged - was explored with different proportions of gold (III) solution in generating gold nanoparticles (GNPs). The progress of the synthesis, which occurred at ambient temperature and pressure and commenced soon after mixing the pistia extracts and gold (III) solutions, was tracked using UV-visible spectrophotometry. The electron micrographs of the synthesized GNPs revealed that, depending on the metal-extract concentrations used in the synthesis, GNPs of either monodispersed spherical shape were formed or there was anisotropy resulting in a mixture of triangular, hexagonal, pentagonal, and truncated triangular shaped GNPs. This phenomenon was witnessed with the extracts of aerial parts as well as submerged parts of pistia. The presence of gold atoms in the nanoparticles was confirmed from the EDAX and X-ray diffraction studies. The FT IR spectral study indicated that the primary and secondary amines associated with the polypeptide biomolecules could have been responsible for the reduction of the gold (III) ions to GNPs and their subsequent stabilization. PMID- 27563462 TI - Eliciting Challenges on Social Connectedness among Filipino Nurse Returnees: A Cross-Sectional Mixed-Method Research. AB - This cross-sectional study utilized a nested concurrent design to determine the association of Filipino nurse returnees' length of stay since they returned and their social connectedness as well as the essence of communication from their perspective. The respondents, who are Filipino nurses (n = 107) who worked abroad and returned to the Philippines for good, were employed from June to July of 2015 via referrals from colleges and institutions in Metro Manila and Bulacan areas in the Philippines. The quantitative results revealed, in one hand, significant but weak correlation between the respondent's length of stay and social connectedness (r = 0.224, p = 0.021, alpha = 0.05). On the other hand, three themes were generated from the qualitative analysis, namely, (1) Taking-In, (2) Taking-Hold, and (3) Letting-Go. The Social Connection System (SCS) provides a visual depiction of the social connectedness of a person. This research is geared towards the understanding of the interesting phenomenon of migration and social coherence of Filipino professionals. PMID- 27563463 TI - Load Handling and Repetitive Movements Are Associated with Chronic Low Back Pain among Jute Mill Workers in India. AB - Introduction. WHO recognizes low back pain as one of the most important ergonomic stressors. Therefore, the present study was designed to find out the magnitude of the problem among jute mill workers in India and identify possible associations. Methodology. This cross-sectional workplace based study was conducted among eight (8) selected jute mills of India. Subjects with self-reported back pain for at least last 12 weeks were included and n = 717 male jute mill workers actively engaged in work entered the study and completed all assessments. Results. Among all participants 55% (n = 392) had current chronic low back pain. Age was an important association with subjects in the age group of 40-59 years more likely to have pain (p = 0.02, OR 1.44). Regarding ergonomic risk factors lifting of load of more than 20 kg (p = 0.04, OR 1.42) and repetitive movements of limbs (p = 0.03, OR 0.67) were significant associations of chronic low back pain. Conclusion. This study identified a significant prevalence of current chronic low back pain among jute mill workers. Regarding ergonomic risk factors the present study has identified two significant associations: lifting of load above 20 kg and repetitive movements of limbs. Therefore, this study has identified need for workplace interventions in this occupational group employing approximately 3,50,000 workers in India. PMID- 27563464 TI - Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection. AB - Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n = 13) or hepatic resection (n = 26) were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (p = 0.011). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS's time-activity-curve (p = 0.001). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX. PMID- 27563465 TI - A Few Observations on Health Service for Immigrants at a Primary Health Care Centre. AB - Objective. Icelandic society is rapidly changing, from being an ethnically homogeneous population towards a multicultural immigrant society. In the hope of optimizing the service for immigrants at the health care centre, we decided to evaluate health care utilization by immigrants. Methods. As a case control study we invited all immigrants that attended the health care centre during a two-week period to participate. Paired controls of Icelanders were invited for comparison. Results. There were 57 immigrants, 48 females and 9 males, from 27 countries. Significantly more of the immigrant women were married, P < 0.001. Interpreters were needed in 21% of the consultations. The immigrants often attended the clinic and had the same diagnoses as did the nonimmigrants. The immigrants evaluated the quality of the service in Iceland as 4.3 and the service in their homeland as 1.68, P < 0.001. Conclusion. Immigrants attending a health care centre in Iceland came from all over the world, had the same diagnoses, and attended the clinic as often per annum as the nonimmigrants. Only one-fifth of them needed translators. The health and health care utilization of immigrants were similar to those of nonimmigrants. PMID- 27563466 TI - EVASEP: A Noninterventional Study Describing the Perception of Neurologists, Patients, and Caregivers on Caregivers' Role in the Support of Patients Suffering from Multiple Sclerosis Treated with Subcutaneous Interferon Beta 1a. AB - Background. The perception of the role of caregivers for people with multiple sclerosis (MS) is important but poorly studied, particularly in patients with low levels of disability. Objectives. To describe the perceptions of the role of caregivers from the perspective of the caregiver, the patient, and neurologists. Methods. This observational study was conducted in France on patients with relapsing remitting MS treated with subcutaneous (SC) interferon-beta-1a (IFN beta-1a) for more than 24 months. Results. Caregiver, patients, and neurologists all considered providing moral support and fighting against the disease as the most important role of the care provider. Moral support was considered significantly more important by caregivers than the patients and neurologists (p = 0.002) and caregivers considered their role in helping patients to fight disease more important than did the neurologists (p = 0.006). Knowledge of disease and available treatments were less important among support providers than patients (p = 0.007 and p = 0.001). Conclusion. There are many unmet needs in the perception of the role of caregivers for people with MS which need to be addressed to deliver the most effective care package for patients and to support the needs of the support provider. PMID- 27563467 TI - Trauma Simulation Training Increases Confidence Levels in Prehospital Personnel Performing Life-Saving Interventions in Trauma Patients. AB - Introduction. Limited evidence is available on simulation training of prehospital care providers, specifically the use of tourniquets and needle decompression. This study focused on whether the confidence level of prehospital personnel performing these skills improved through simulation training. Methods. Prehospital personnel from Alachua County Fire Rescue were enrolled in the study over a 2- to 3-week period based on their availability. Two scenarios were presented to them: a motorcycle crash resulting in a leg amputation requiring a tourniquet and an intoxicated patient with a stab wound, who experienced tension pneumothorax requiring needle decompression. Crews were asked to rate their confidence levels before and after exposure to the scenarios. Timing of the simulation interventions was compared with actual scene times to determine applicability of simulation in measuring the efficiency of prehospital personnel. Results. Results were collected from 129 participants. Pre- and postexposure scores increased by a mean of 1.15 (SD 1.32; 95% CI, 0.88-1.42; P < 0.001). Comparison of actual scene times with simulated scene times yielded a 1.39-fold difference (95% CI, 1.25-1.55) for Scenario 1 and 1.59 times longer for Scenario 2 (95% CI, 1.43-1.77). Conclusion. Simulation training improved prehospital care providers' confidence level in performing two life-saving procedures. PMID- 27563468 TI - Synchrotron Radiation X-Ray Phase-Contrast Tomography Visualizes Microvasculature Changes in Mice Brains after Ischemic Injury. AB - Imaging brain microvasculature is important in plasticity studies of cerebrovascular diseases. Applying contrast agents, traditional MUCT and MUMRI methods gain imaging contrast for vasculature. The aim of this study is to develop a synchrotron radiation X-ray inline phase-contrast tomography (SRXPCT) method for imaging the intact mouse brain (micro)vasculature in high resolution (~3.7 MUm) without contrast agent. A specific preparation protocol was proposed to enhance the phase contrast of brain vasculature by using density difference over gas-tissue interface. The CT imaging system was developed and optimized to obtain 3D brain vasculature of adult male C57BL/6 mice. The SRXPCT method was further applied to investigate the microvasculature changes in mouse brains (n = 14) after 14-day reperfusion from transient middle cerebral artery occlusion (tMCAO). 3D reconstructions of brain microvasculature demonstrated that the branching radius ratio (post- to preinjury) of small vessels (radius < 7.4 MUm) in the injury group was significantly smaller than that in the sham group (p < 0.05). This result revealed the active angiogenesis in the recovery brain after stroke. As a high-resolution and contrast-agent-free method, the SRXPCT method demonstrates higher potential in investigations of functional plasticity in cerebrovascular diseases. PMID- 27563471 TI - Ventricular Septal Defect from Takotsubo Syndrome. AB - Takotsubo Syndrome is a transient condition characterized by left ventricular systolic dysfunction with apical akinesis/dyskinesis and ballooning. Although the prognosis with medical management is excellent in most cases, rare cases of serious complications can occur. We present here a case of a 71-year-old woman presenting with acute decompensated heart failure with initial findings consistent with a myocardial infarction, who was found instead to have an acute ventricular septal defect as a complication of Takotsubo Syndrome. PMID- 27563470 TI - Mirror Visual Feedback to Improve Bradykinesia in Parkinson's Disease. AB - Mirror visual feedback (MVF) therapy has been applied to improve upper limb function in stroke. When combined with motor training, MVF improves the performance of the trained and untrained hand by enhancing the excitability of both primary motor cortices (M1s). Bradykinesia is a typical feature of Parkinson's disease (PD), characterized by slowness in the execution of movement. This condition is often asymmetrical and possibly supported by a volitional hypoactivation of M1. MVF therapy could tentatively treat bradykinesia since the untrained hand, which benefits from the exercise, is generally more severely impaired in undertaking sequential movements. Aim of the study was to evaluate whether MVF therapy may improve bradykinesia of the more affected hand in PD patients. Twelve PD patients and twelve healthy controls performed for 10 minutes a finger sequence, receiving MVF of the more affected/nondominant hand. Before and after MVF training, participants performed a finger sequence at their spontaneous pace with both hands. M1 excitability was assessed in the trained and untrained hemispheres by means of transcranial magnetic stimulation. Movement speed increased after MVF training in either hand of both groups. MVF therapy enhanced cortical excitability of M1s in both groups. Our preliminary data support the use of MVF therapy to improve bradykinesia in PD patients. PMID- 27563472 TI - Severe Methemoglobinemia due to Sodium Nitrite Poisoning. AB - Case. We report a case of severe methemoglobinemia due to sodium nitrite poisoning. A 28-year-old man was brought to our emergency department because of transient loss of consciousness and cyanosis. He was immediately intubated and ventilated with 100% oxygen. A blood test revealed a methemoglobin level of 92.5%. Outcome. We treated the patient with gastric lavage, activated charcoal, and methylene blue (2 mg/kg) administered intravenously. Soon after receiving methylene blue, his cyanosis resolved and the methemoglobin level began to decrease. After relocation to the intensive care unit, his consciousness improved and he could recall ingesting approximately 15 g sodium nitrite about 1 hour before he was brought to our hospital. The patient was discharged on day 7 without neurologic impairment. Conclusion. Severe methemoglobinemia may be fatal. Therefore, accurate diagnosis of methemoglobinemia is very important so that treatment can be started as soon as possible. PMID- 27563469 TI - Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons. AB - High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth. PMID- 27563473 TI - A Rare Cause of Hemophagocytic Lymphohistiocytosis: Fusobacterium Infection-A Case Report and Review of the Literature. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by excessive activation of the immune system. Bacterial infections are very rare precipitants of this disease. A 19-year-old gentleman presented with headache, fatigue, and malaise. He was found to be hypotensive, tachycardic, and febrile. Broad spectrum antibiotics were initiated, and a lumbar puncture ruled out meningitis. Patient progressively developed shock that required use of vasopressors, as well as renal and respiratory failure. Blood cultures grew Fusobacterium necrophorum. Given continued fevers despite appropriate antimicrobials, a bone marrow biopsy was performed revealing increased histiocytes with hemophagocytosis. Dexamethasone was added with dramatic clinical improvement. Our case highlights Fusobacterium as a rare precipitant of HLH and proves that a high index of clinical suspicion is crucial for early diagnosis of HLH, allowing for prompt initiation of HLH-specific immunosuppressive therapy that can be life-saving. PMID- 27563474 TI - Steroid Refractory Autoimmune Haemolytic Anaemia Secondary to Sarcoidosis Successfully Treated with Rituximab and Mycophenolate Mofetil. AB - Autoimmune haemolytic anaemia is not a well-recognised complication of sarcoidosis. We describe the case of a 30-year-old female who presented with acute warm haemolytic anaemia and widespread lymphadenopathy. Sarcoidosis was diagnosed on lymph node biopsy and further investigation. The haemolytic anaemia responded only to a high dose of steroids. Evidence regarding treatment of steroid refractory autoimmune haemolysis secondary to sarcoidosis is lacking. Based on the emergent evidence that both disorders share common immunopathogenic mechanisms involving Th1 and Th17 lymphocytes, our patient was given rituximab and mycophenolate mofetil to successfully suppress the haemolysis and sarcoid activity. PMID- 27563475 TI - Gastric Medullary Carcinoma: A Rare Case Report. AB - A case of 64-year-old female patient with early stage gastric medullary carcinoma has been presented, along with a review of the literature. PMID- 27563476 TI - Synovial Lipomatosis of the Glenohumeral Joint. AB - Synovial lipomatosis (also known as lipoma arborescens) is a rare and benign lesion affecting synovium-lined cavities. It is characterized by hyperplasia of mature fat tissue in the subsynovial layer. Although the most commonly affected site is the knee joint, rarely additional locations such as tendon sheath and other joints are involved. We present a case of synovial lipomatosis of the glenohumeral joint in a 44-year-old man. The clinical data radiological studies and histopathologic results are described, as well as a review of the current literature. PMID- 27563477 TI - A Scaphoid Stress Fracture in a Female Collegiate-Level Shot-Putter and Review of the Literature. AB - Scaphoid stress fractures are rare injuries that have been described in young, high-level athletes who exhibit repetitive loading with the wrist in extension. We present a case of an occult scaphoid stress fracture in a 22-year-old female Division I collegiate shot-putter. She was successfully treated with immobilization in a thumb spica splint for 6 weeks. Loaded wrist extension activities can predispose certain high-level athletes to sustain scaphoid stress fractures, and a high index of suspicion in this patient population may aid prompt diagnosis and management of this rare injury. PMID- 27563478 TI - Orbital Metastasis of Breast Cancer Mimicking Invasive Fungal Rhinosinusitis. AB - Introduction. A range of traumatic, vascular, inflammatory, infectious, and neoplastic processes can affect the orbit and its structures. In the area of otolaryngology, the rhino-orbital-cerebral involvement of invasive fungal rhinosinusitis can affect the orbit, which may look like initially a rhinosinusitis or even mimic malignancy. Case Presentation. Female patient, 32 years old, with headache and ocular proptosis. She was using prednisone in immunosuppressive doses for a year and had breast cancer treated three years earlier. The initial CT scan showed opacification of the sphenoid and ethmoid sinuses, left intraorbital involvement and contrast impregnation in the cavernous sinus. The biopsy resulted positive for invasive ductal carcinoma of the breast. Discussion. The initial CT scan of our patient showed both signs of early changes of invasive fungal rhinosinusitis (IFR) and possible metastatic involvement. The intracranial extension and ocular involvement are usually the most common signs of IFR (first hypothesis). Among metastases at the orbit and the eye, breast and lung carcinomas are the most frequent. Conclusion. Although several studies on the differential diagnosis of orbital lesions exist, especially when it concerns the involvement of the nasal cavity, the diagnosis by imaging is still a challenge. PMID- 27563479 TI - Undifferentiated Pleomorphic Sarcoma Presenting as Abdominal Pain with a Pulsatile Mass. AB - Malignant fibrous histiocytoma (MFH) is a rare tumor that mostly involves adults aged 50 to 70. The most common anatomic location is the lower extremities. MFH of the retroperitoneum usually manifests late in its course and may be initially mistaken with other more common diagnosis. Here, the authors describe a 60-year old man that was brought to the emergency department with a chief complaint of periumbilical abdominal pain. Our patient presented with symptoms consistent with a symptomatic aortic aneurysm, but a mass was encountered during surgery. In such circumstances the diagnosis of malignant sarcoma must be kept in mind and attempts at full resection with tumor-free margins are necessary. PMID- 27563480 TI - Impact of Rosuvastatin Treatment on HDL-Induced PKC-betaII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure. AB - Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser(1177), dephosphorylation at Thr(495), and diminished phosphorylation of PKC-betaII at Ser(660). The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-betaII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-betaII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-betaII. Conclusion. HDL mediated eNOS and PKC-betaII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function. PMID- 27563481 TI - Interpretation Criteria for Comparative Intradermal Tuberculin Test for Diagnosis of Bovine Tuberculosis in Cattle in Maroua Area of Cameroon. AB - Intradermal tuberculin test (TST) is the choice method for diagnosis of bovine tuberculosis (Tb) in live animals. This work was done to assess the performance of single intradermal comparative cervical tuberculin (SICCT) test in randomly selected cattle in Maroua, Cameroon, against detection of Tb lesions and detection of Tb lesions plus acid fast bacilli in lesions. While 22.28% of slaughtered cattle presented Tb lesions at meat inspection, detection rates of anti-bovine-Tb antibody, Tb lesions, and Tb lesions plus acid fast bacilli were 68.57%, 32.95%, and 22.35%, respectively. SICCT-bovine-Tb positive cattle were 35.29%, 29.41%, 25.88%, 24.7%, and 21.18% at >=2 mm, >=2.5 mm, >=3 mm, >=3.5 mm, and >=4 mm cut-offs, respectively. Higher sensitivity and predictive values were obtained at severe interpretations. The best performance was at >=3 mm and >=3.5 mm cut-offs. Against detection of Tb lesions, >=3 mm and >=3.5 mm showed sensitivity of 67.8% and specificity of 94.7% and 96.5%, respectively. For detection of Tb lesions accompanied with acid fast bacilli in lesions, >=3 mm and >=3.5 mm showed sensitivity of 89.4% and specificity of 92.4% and 93.9%, respectively. These findings revealed that interpretations of SICCT-bovine-Tb should be at >=3 mm and/or >=3.5 mm cut-offs. Severe interpretation of TST is essential for optimal diagnosis of bovine Tb in cattle in Maroua, Cameroon. PMID- 27563482 TI - Integration of Andrographis paniculata as Potential Medicinal Plant in Chir Pine (Pinus roxburghii Sarg.) Plantation of North-Western Himalaya. AB - The integration of Andrographis paniculata under Pinus roxburghii (Chir pine) plantation has been studied to evaluate the growth and yield for its economic viability and conservation. It was grown on three topographical aspects, namely, northern, north-western, and western, at a spacing of 30 cm * 30 cm, followed by three tillage depths, namely, minimum (0 cm), medium (up to 10 cm), and deep (up to 15 cm) tillage. The growth parameters, namely, plant height and number of branches per plant, were recorded as significantly higher on western aspect and lowest on northern aspect except for leaf area index which was found nonsignificant. However under all tillage practices all the growth parameters in both understorey and open conditions were found to be nonsignificant except for plant height which was found to be significantly highest under deep tillage and lowest under minimum tillage. The study of net returns for Andrographis paniculata revealed that it had positive average annual returns even in understorey conditions which indicate its possible economic viability under integration of Chir pine plantations. Hence net returns can be enhanced by integrating Andrographis paniculata and this silvimedicinal system can be suggested which will help utilizing an unutilized part of land and increase total productivity from such lands besides conservation of the A. paniculata in situ. PMID- 27563483 TI - Clinical Behavior of Bladder Urothelial Carcinoma in Young Patients: A Single Center Experience. AB - Background. There is not enough evidence about clinical behavior of bladder cancer in younger patients. Objective. We aimed to evaluate the clinical characteristics and prognosis of bladder urothelial carcinoma patients under the age of 40 years. Methods. Medical records of patients listed in our cancer database were retrospectively reviewed. A total of 40 patients who were initially diagnosed with bladder urothelial carcinoma at the age less than 40 years were included in the study. Patients' records were reviewed for recurrence and progression rates, demographic data, medical history, and treatment modalities. Results. Pathological results revealed 33 (82.5%) Ta low-grade, 6 (15%) T1 high grade, and 1 (2.5%) T2 high-grade urothelial carcinomas. Recurrence was detected in 14/39 (35.9%) patients but progression was not observed in any patients. The mean age of recurrent patients was significantly higher than nonrecurrent patients (34.8 versus 28.5 years; p < 0.05). Besides, recurrence was detected in only 1 patient with the age under 30 years (6.2%) and 13 patients (54.1%) between 30 and 40 years old, respectively (p < 0.05). Conclusion. Bladder urothelial carcinoma diagnosed at young age tends to be a low pathologic stage, with relatively low rate of recurrence and progression. PMID- 27563485 TI - Brain abscess caused by Nocardia asiatica. AB - BACKGROUND: Nocardia infection of the central nervous system leading to brain abscess is a rare condition but has a high mortality rate. Among the species of Nocardia, only three cases of brain abscess due to Nocardia asiatica infection have been reported. CASE DESCRIPTION: A 65-year-old man with a history of autoimmune hemolytic anemia treated with prednisolone presented to our hospital because of occipital headache. Brain magnetic resonance imaging showed bilateral occipital lesions. The patient underwent craniotomy and resection of the left occipital lobe lesion. N. asiatica was identified by 16S rRNA sequencing of the resected specimen. Treatment with trimethoprim/sulfamethoxazole led to a complete resolution of the brain lesion. CONCLUSION: Because of the different antimicrobial sensitivity patterns among Nocardia species, both appropriate subtyping and susceptibility testing of uncommon species such as N. asiatica are required for the successful treatment of nocardial infections. PMID- 27563487 TI - Clinically-inspired automatic classification of ovarian carcinoma subtypes. AB - CONTEXT: It has been shown that ovarian carcinoma subtypes are distinct pathologic entities with differing prognostic and therapeutic implications. Histotyping by pathologists has good reproducibility, but occasional cases are challenging and require immunohistochemistry and subspecialty consultation. Motivated by the need for more accurate and reproducible diagnoses and to facilitate pathologists' workflow, we propose an automatic framework for ovarian carcinoma classification. MATERIALS AND METHODS: Our method is inspired by pathologists' workflow. We analyse imaged tissues at two magnification levels and extract clinically-inspired color, texture, and segmentation-based shape descriptors using image-processing methods. We propose a carefully designed machine learning technique composed of four modules: A dissimilarity matrix, dimensionality reduction, feature selection and a support vector machine classifier to separate the five ovarian carcinoma subtypes using the extracted features. RESULTS: This paper presents the details of our implementation and its validation on a clinically derived dataset of eighty high-resolution histopathology images. The proposed system achieved a multiclass classification accuracy of 95.0% when classifying unseen tissues. Assessment of the classifier's confusion (confusion matrix) between the five different ovarian carcinoma subtypes agrees with clinician's confusion and reflects the difficulty in diagnosing endometrioid and serous carcinomas. CONCLUSIONS: Our results from this first study highlight the difficulty of ovarian carcinoma diagnosis which originate from the intrinsic class-imbalance observed among subtypes and suggest that the automatic analysis of ovarian carcinoma subtypes could be valuable to clinician's diagnostic procedure by providing a second opinion. PMID- 27563486 TI - Pathology Informatics Essentials for Residents: A flexible informatics curriculum linked to Accreditation Council for Graduate Medical Education milestones. AB - CONTEXT: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics have been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. OBJECTIVE: The objective of the study is to develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills and meets Accreditation Council for Graduate Medical Education Informatics Milestones. DESIGN: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. RESULTS: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). CONCLUSIONS: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time. PMID- 27563488 TI - Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases. AB - BACKGROUND: Deep learning (DL) is a representation learning approach ideally suited for image analysis challenges in digital pathology (DP). The variety of image analysis tasks in the context of DP includes detection and counting (e.g., mitotic events), segmentation (e.g., nuclei), and tissue classification (e.g., cancerous vs. non-cancerous). Unfortunately, issues with slide preparation, variations in staining and scanning across sites, and vendor platforms, as well as biological variance, such as the presentation of different grades of disease, make these image analysis tasks particularly challenging. Traditional approaches, wherein domain-specific cues are manually identified and developed into task specific "handcrafted" features, can require extensive tuning to accommodate these variances. However, DL takes a more domain agnostic approach combining both feature discovery and implementation to maximally discriminate between the classes of interest. While DL approaches have performed well in a few DP related image analysis tasks, such as detection and tissue classification, the currently available open source tools and tutorials do not provide guidance on challenges such as (a) selecting appropriate magnification, (b) managing errors in annotations in the training (or learning) dataset, and (c) identifying a suitable training set containing information rich exemplars. These foundational concepts, which are needed to successfully translate the DL paradigm to DP tasks, are non trivial for (i) DL experts with minimal digital histology experience, and (ii) DP and image processing experts with minimal DL experience, to derive on their own, thus meriting a dedicated tutorial. AIMS: This paper investigates these concepts through seven unique DP tasks as use cases to elucidate techniques needed to produce comparable, and in many cases, superior to results from the state-of-the art hand-crafted feature-based classification approaches. RESULTS: Specifically, in this tutorial on DL for DP image analysis, we show how an open source framework (Caffe), with a singular network architecture, can be used to address: (a) nuclei segmentation (F-score of 0.83 across 12,000 nuclei), (b) epithelium segmentation (F-score of 0.84 across 1735 regions), (c) tubule segmentation (F score of 0.83 from 795 tubules), (d) lymphocyte detection (F-score of 0.90 across 3064 lymphocytes), (e) mitosis detection (F-score of 0.53 across 550 mitotic events), (f) invasive ductal carcinoma detection (F-score of 0.7648 on 50 k testing patches), and (g) lymphoma classification (classification accuracy of 0.97 across 374 images). CONCLUSION: This paper represents the largest comprehensive study of DL approaches in DP to date, with over 1200 DP images used during evaluation. The supplemental online material that accompanies this paper consists of step-by-step instructions for the usage of the supplied source code, trained models, and input data. PMID- 27563489 TI - Comparing whole slide digital images versus traditional glass slides in the detection of common microscopic features seen in dermatitis. AB - BACKGROUND: The quality and limitations of digital slides are not fully known. We aimed to estimate intrapathologist discrepancy in detecting specific microscopic features on glass slides and digital slides created by scanning at *20. METHODS: Hematoxylin and eosin and periodic acid-Schiff glass slides were digitized using the Mirax Scan (Carl Zeiss Inc., Germany). Six pathologists assessed 50-71 digital slides. We recorded objective magnification, total time, and detection of the following: Mast cells; eosinophils; plasma cells; pigmented macrophages; melanin in the epidermis; fungal bodies; neutrophils; civatte bodies; parakeratosis; and sebocytes. This process was repeated using the corresponding glass slides after 3 weeks. The diagnosis was not required. RESULTS: The mean time to assess digital slides was 176.77 s and 137.61 s for glass slides (P < 0.001, 99% confidence interval [CI]). The mean objective magnification used to detect features using digital slides was 18.28 and 14.07 for glass slides (P < 0.001, 99.99% CI). Parakeratosis, civatte bodies, pigmented macrophages, melanin in the epidermis, mast cells, eosinophils, plasma cells, and neutrophils, were identified at lower objectives on glass slides (P = 0.023-0.001, 95% CI). Average intraobserver concordance ranged from kappa = 0.30 to kappa = 0.78. Features with poor to fair average concordance were: Melanin in the epidermis (kappa = 0.15 0.58); plasma cells (kappa = 0.15-0.49); and neutrophils (kappa = 0.12-0.48). Features with moderate average intrapathologist concordance were: parakeratosis (kappa = 0.21-0.61); civatte bodies (kappa = 0.21-0.71); pigment-laden macrophages (kappa = 0.34-0.66); mast cells (kappa = 0.29-0.78); and eosinophils (kappa = 0.31-0.79). The average intrapathologist concordance was good for sebocytes (kappa = 0.51-1.00) and fungal bodies (kappa = 0.47-0.76). CONCLUSIONS: Telepathology using digital slides scanned at *20 is sufficient for detection of histopathologic features routinely encountered in dermatitis cases, though less efficient than glass slides. PMID- 27563490 TI - NDER: A novel web application using annotated whole slide images for rapid improvements in human pattern recognition. AB - CONTEXT: Whole-slide images (WSIs) present a rich source of information for education, training, and quality assurance. However, they are often used in a fashion similar to glass slides rather than in novel ways that leverage the advantages of WSI. We have created a pipeline to transform annotated WSI into pattern recognition training, and quality assurance web application called novel diagnostic electronic resource (NDER). AIMS: Create an efficient workflow for extracting annotated WSI for use by NDER, an attractive web application that provides high-throughput training. MATERIALS AND METHODS: WSI were annotated by a resident and classified into five categories. Two methods of extracting images and creating image databases were compared. Extraction Method 1: Manual extraction of still images and validation of each image by four breast pathologists. Extraction Method 2: Validation of annotated regions on the WSI by a single experienced breast pathologist and automated extraction of still images tagged by diagnosis. The extracted still images were used by NDER. NDER briefly displays an image, requires users to classify the image after time has expired, then gives users immediate feedback. RESULTS: The NDER workflow is efficient: annotation of a WSI requires 5 min and validation by an expert pathologist requires An additional one to 2 min. The pipeline is highly automated, with only annotation and validation requiring human input. NDER effectively displays hundreds of high-quality, high-resolution images and provides immediate feedback to users during a 30 min session. CONCLUSIONS: NDER efficiently uses annotated WSI to rapidly increase pattern recognition and evaluate for diagnostic proficiency. PMID- 27563484 TI - TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. AB - Transforming growth factor-beta (TGF-beta) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-betas and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-beta/BMP ligands, receptors, and Smads) and the non-canonical-Smad independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-beta and BMP signaling is controlled by multiple factors, including the ubiquitin-proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-beta and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-beta and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-beta/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-beta/BMP signaling and several critical cytokines' signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-beta/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-beta/BMP signaling. PMID- 27563491 TI - Improving the creation and reporting of structured findings during digital pathology review. AB - BACKGROUND: Today, pathology reporting consists of many separate tasks, carried out by multiple people. Common tasks include dictation during case review, transcription, verification of the transcription, report distribution, and report the key findings to follow-up registries. Introduction of digital workstations makes it possible to remove some of these tasks and simplify others. This study describes the work presented at the Nordic Symposium on Digital Pathology 2015, in Linkoping, Sweden. METHODS: We explored the possibility to have a digital tool that simplifies image review by assisting note-taking, and with minimal extra effort, populates a structured report. Thus, our prototype sees reporting as an activity interleaved with image review rather than a separate final step. We created an interface to collect, sort, and display findings for the most common reporting needs, such as tumor size, grading, and scoring. RESULTS: The interface was designed to reduce the need to retain partial findings in the head or on paper, while at the same time be structured enough to support automatic extraction of key findings for follow-up registry reporting. The final prototype was evaluated with two pathologists, diagnosing complicated partial mastectomy cases. The pathologists experienced that the prototype aided them during the review and that it created a better overall workflow. CONCLUSIONS: These results show that it is feasible to simplify the reporting tasks in a way that is not distracting, while at the same time being able to automatically extract the key findings. This simplification is possible due to the realization that the structured format needed for automatic extraction of data can be used to offload the pathologists' working memory during the diagnostic review. PMID- 27563492 TI - Ruthenium-Catalyzed C-H Bond Activation Approach to Azolyl Aminals and Hemiaminal Ethers, Mechanistic Evaluations, and Isomer Interconversion. AB - C(sp3)-N bond-forming reactions between benzotriazole and 5,6 dimethylbenzotriazole with N-methylpyrrolidinone, tetrahydrofuran, tetrahydropyran, diethyl ether, 1,4-dioxane, and isochroman have been conducted using RuCl3*3H2O/t-BuOOH in 1,2-dichloroethane. In all cases, N1 and N2 alkylation products were obtained, and these are readily separated by chromatography. One of these products, 1-(isochroman-1-yl)-5,6-dimethyl-1H benzotriazole, was examined by X-ray crystallography. It is the first such compound to be analyzed by this method, and notably, the benzotriazolyl moiety is quasi-axially disposed, consistent with the anomeric effect. This has plausible consequences, not observed previously. In contrast to other hemiaminal ether forming reactions, which proceed via radicals, this Ru-catalyzed process is not suppressed in the presence of a radical inhibitor. Therefore, an oxoruthenium species-mediated rapid formation of an oxocarbenium intermediate is believed to occur. In the radical-trapping experiment, previously unknown products containing both the benzotriazole and the TEMPO unit have been identified. In these products, it is likely that the benzotriazole is introduced via a Ru-catalyzed C N bond formation, whereas C-O bond-formation with TEMPO occurs via a radical reaction. We show that reactions of THF with TEMPO are influenced by ambient light. A competitive reaction of THF and THF-d8 with benzotriazole indicated that C-H bond cleavage occurs ca. 5 times faster than C-D cleavage. This is comparable to other metal-mediated radical reactions of THF, but lower than that observed for a reaction catalyzed by n-Bu4N+I-. Detailed mechanistic experiments and comparisons are described. The catalytic system was also evaluated for reactions of benzimidazole, imidazole, 1,2,4-triazole, and 1,2,3-triazole with THF, and successful reactions were achieved in each case. In the course of our studies, we discovered an unexpected but significant isomerization of some of the benzotriazolyl hemiaminal ethers. This is plausibly attributable to the pseudoaxial orientation of the heterocycle in the products and the stability of oxocarbenium ions, both of which can contribute to C-N bond cleavage and reformation. Predominantly, the N2-isomers rearrange to the N1-isomers even upon storage at low temperature! This previously unknown phenomenon has also been studied and described. PMID- 27563493 TI - Correlating Calmodulin Landscapes with Chemical Catalysis in Neuronal Nitric Oxide Synthase using Time-Resolved FRET and a 5-Deazaflavin Thermodynamic Trap. AB - A major challenge in enzymology is the need to correlate the dynamic properties of enzymes with, and understand the impact on, their catalytic cycles. This is especially the case with large, multicenter enzymes such as the nitric oxide synthases (NOSs), where the importance of dynamics has been inferred from a variety of structural, single-molecule, and ensemble spectroscopic approaches but where motions have not been correlated experimentally with mechanistic steps in the reaction cycle. Here we take such an approach. Using time-resolved spectroscopy employing absorbance and Forster resonance energy transfer (FRET) and exploiting the properties of a flavin analogue (5-deazaflavin mononucleotide (5-dFMN)) and isotopically labeled nicotinamide coenzymes, we correlate the timing of CaM structural changes when bound to neuronal nitric oxide synthase (nNOS) with the nNOS catalytic cycle. We show that remodeling of CaM occurs early in the electron transfer sequence (FAD reduction), not at later points in the reaction cycle (e.g., FMN reduction). Conformational changes are tightly correlated with FAD reduction kinetics and reflect a transient "opening" and then "closure" of the bound CaM molecule. We infer that displacement of the C-terminal tail on binding NADPH and subsequent FAD reduction are the likely triggers of conformational change. By combining the use of cofactor/coenzyme analogues and time-resolved FRET/absorbance spectrophotometry, we show how the reaction cycles of complex enzymes can be simplified, enabling a detailed study of the relationship between protein dynamics and reaction cycle chemistry-an approach that can also be used with other complex multicenter enzymes. PMID- 27563494 TI - Interleukin-4 Expressed By Neoplastic Cells Provokes an Anti-Metastatic Myeloid Immune Response. AB - OBJECTIVE: Interleukin-4 (IL-4) can induce macrophages to undergo alternative activation and polarize toward an M2-like or wound healing phenotype. Tumor associated macrophages (TAMs) are thought to assume M2-like properties, and it has been suggested they promote tumor growth and metastasis through effects on the tumor stroma, including extracelluar matrix remodeling and angiogenesis. IL-4 also promotes macrophage survival and formation of multinucleated giant cells, which have enhanced phagocytic behavior. This study was designed to explore the effect of cancer cell derived IL-4 on the tumor immune stroma and metastasis. METHODS: The metastatic mouse mammary carcinoma cell line AC2M2 was transduced with control or IL-4 encoding retroviruses and employed in orthotopic engraftment models. Tumor growth and metastasis were assessed. The cellular composition and biomarker expression of tumors were examined by immunohistochemical staining and flow cytometry; the transcriptome of the immune stroma was analyzed by nanoString based transcript quantitation; and in vivo and in vitro interactions between cancer cells and macrophages were assessed by flow cytometry and co-culture with video-time lapse microscopy, respectively. RESULTS: Unexpectedly, tumors from IL 4 expressing AC2M2 engrafted cells grew at reduced rates, and most surprising, they lost all metastatic potential relative to tumors from control AC2M2 cells. Myeloid cell numbers were not increased in IL-4 expressing tumors, but their expression of the M2 marker arginase I was elevated. Transcriptome analysis revealed an immune signature consistent with IL-4 induced M2 polarization of the tumor microenvironment and a generalized increase in myeloid involvement in the tumor stroma. Flow cytometry analysis indicated enhanced cancer cell phagocytosis by TAMs from IL-4 expressing tumors, and co-culture studies showed that IL-4 expressing cancer cells supported the survival and promoted the in vitro phagocytic behavior of macrophages. CONCLUSIONS: Although M2-like TAMs have been linked to enhanced tumorigenesis, this study shows that IL-4 production by cancer cells is associated with suppressed tumor growth and loss of metastatic potential as well as enhanced phagocytic behavior of TAMs. PMID- 27563495 TI - Transjugular Intrahepatic Portosystemic Shunt Dysfunction: Concordance of Clinical Findings, Doppler Ultrasound Examination, and Shunt Venography. AB - OBJECTIVES: The objective of this study was to evaluate the concordance between clinical symptoms, Doppler ultrasound (US), and shunt venography for the detection of stent-graft transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. MATERIALS AND METHODS: Forty-one patients (M:F 30:11, median age 55 years) who underwent contemporaneous clinical exam, Doppler US, and TIPS venography between 2003 and 2014 were retrospectively studied. Clinical symptoms (recurrent ascites or variceal bleeding) were dichotomously classified as present/absent, and US and TIPS venograms were categorized in a binary fashion as normal/abnormal. US abnormalities included high/low (>190 or <90 cm/s) TIPS velocity, significant velocity rise/fall (>50 cm/s), absent flow, and return of antegrade intra-hepatic portal flow. Venographic abnormalities included shunt stenosis/occlusion and/or pressure gradient elevation. Clinical and imaging concordance rates were calculated. RESULTS: Fifty-two corresponding US examinations and venograms were assessed. The median time between studies was 3 days. Forty of 52 (77%) patients were symptomatic, 33/52 (64%) US examinations were abnormal, and 20/52 (38%) TIPS venograms were abnormal. Concordance between clinical symptoms and TIPS venography was 48% (25/52), while the agreement between US and shunt venography was 65% (34/52). Clinical symptoms and the US concurred in 60% (31/52) of the patients. The sensitivity of clinical symptoms and US for the detection of venographically abnormal shunts was 80% (16/20) and 85% (17/20), respectively. Both clinical symptoms and the US had low specificity (25%, 8/32 and 50%, 16/32) for venographically abnormal shunts. CONCLUSION: Clinical findings and the US had low concordance rates with TIPS venography, with acceptable sensitivity but poor specificity. These findings suggest the need for improved noninvasive imaging methods for stent-graft TIPS surveillance. PMID- 27563496 TI - CORRIGENDUM. AB - [This corrects the article on p. 888 in vol. 9, PMID: 25540704.]. PMID- 27563497 TI - Caring for Pregnant Women with Opioid Use Disorder in the USA: Expanding and Improving Treatment. AB - PURPOSE OF THE REVIEW: Opioid use disorder in the USA is rising at an alarming rate, particularly among women of childbearing age. Pregnant women with opioid use disorder face numerous barriers to care, including limited access to treatment, stigma, and fear of legal consequences. This review of opioid use disorder in pregnancy is designed to assist health care providers caring for pregnant and postpartum women with the goal of expanding evidence-based treatment practices for this vulnerable population. RECENT FINDINGS: We review current literature on opioid use disorder among US women, existing legislation surrounding substance use in pregnancy, and available treatment options for pregnant women with opioid use disorder. Opioid agonist treatment (OAT) remains the standard of care for treating opioid use disorder in pregnancy. Medically assisted opioid withdrawal ("detoxification") is not recommended in pregnancy and is associated with high maternal relapse rates. Extended release naltrexone may confer benefit for carefully selected patients. Histories of trauma and mental health disorders are prevalent in this population; and best practice recommendations incorporate gender-specific, trauma-informed, mental health services. Breastfeeding with OAT is safe and beneficial for the mother-infant dyad. SUMMARY: Further research investigating options of OAT and the efficacy of opioid antagonists in pregnancy is needed. The US health care system can adapt to provide quality care for these mother-infant dyads by expanding comprehensive treatment services and improving access to care. PMID- 27563498 TI - The Association Between Socio-demographic Factors, Dental Problems, and Preterm Labor for Pregnant Women Residing in Hawai'i. AB - Periodontal disease during pregnancy has the potential to increase the risk of adverse perinatal outcomes including preterm labor (PTL), prematurity, and low birth weight (LBW). Despite professional recommendations on the importance and safety of dental assessments and treatments, the rate of dental care utilization during pregnancy remains low. The purpose of this study was to document the utilization of dental services and explore the relationships among socio demographic factors, dental problems, and PTL in pregnant women residing in Hawai'i. Hawai'i Pregnancy Risk Assessment Monitoring System (PRAMS) survey results were analyzed from 4,309 women who experienced live births between the years 2009-2011. Results revealed that 2 in 5 women in Hawai'i had their teeth cleaned during pregnancy, while 1 in 5 reported seeing a dentist for a dental problem. Women who reported having a dental problem during pregnancy were more likely to experience PTL (OR=1.46, 95% CI=1.10-1.94, P=.008) compared to women without a dental problem. In addition, Native Hawaiian and Part-Hawaiian women were more likely to experience PTL (OR=1.73, 95% CI=1.22-2.46, P=.002) compared to Caucasian women. These findings document the underutilization of dental services in pregnant women in Hawai'i and reveal an association between poor dental care and PTL. Identification of groups at risk for maternal complications may assist in the development of programs that are sensitive to the diverse cultures and variability of community resources that exist throughout Hawai'i. PMID- 27563499 TI - Disparate Rates of Utilization and Progression to Combined Heart Failure and Chronic Obstructive Pulmonary Disease among Asians and Pacific Islanders in Hawai'i. AB - The objectives of the study were to compare ethnic differences in the rates of emergency department (ED) visits and hospitalizations, and to examine ethnic differences in how quickly patients with either chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) developed both diseases. A large health plan in Hawai.i provided administrative data (2007 to 2010) on patients of Native Hawaiian, Japanese, Chinese, Filipino, and White race/ethnicity. The study found distinct patterns of health risks among the multi-ethnic population of patients with COPD, CHF, or both conditions. Native Hawaiians had the highest rates of ED visits and hospitalizations. Japanese, the largest ethnic group and relatively low health risks, were selected as the reference population. In adjusted regression models, Filipino patients with CHF developed COPD the most rapidly; 71% faster than Japanese patients. Compared to Japanese, Native Hawaiians with COPD transitioned to CHF 68% faster. The study highlights ethnic disparities in adverse events and disease progression in patients with COPD and CHF, with important implications for clinical practice. Health care providers may want to inform patients of ways to mitigate the risks. PMID- 27563501 TI - Medical School Hotline: A Canadian's Journey through JABSOM's Waters. PMID- 27563500 TI - What's the Plan? Needing Assistance with Plan of Care Is Associated with In Hospital Death for ICU Patients Referred for Palliative Care Consultation. AB - To inform earlier identification of intensive care unit (ICU) patients needing palliative care, we examined factors associated with in-hospital death among ICU patients (N=260) receiving palliative care consultations at a 542-bed tertiary care hospital (2005-2009). High pre-consultation length of stay (LOS, >=7 days) (adjusted odds ratio (aOR)=5.0, 95% confidence interval (95% CI)=2.5-9.9, P<.01) and consultations for assistance with plan of care (aOR=11.6, 95% CI=5.6-23.9, P<.01) were independently associated with in-hospital death. Patients with both consultation for plan of care and high pre-consult LOS had the highest odds of in hospital death (aOR=36.3, 95% CI=14.9-88.5, P<.001), followed by patients with consultation for plan of care and shorter pre-consult LOS (aOR=9.8, 95% CI=4.3 22.1, P<.001), and patients with long pre-consult LOS but no consultation for plan of care (aOR=4.7, 95% CI=1.8-12.4, P=.002). Our findings suggest that ICU patients who require assistance with plan of care need to be identified early to optimize end-of-life care and avoid in-hospital death. PMID- 27563502 TI - Insights in Public Health: Climate Change: A Public Health Challenge and Opportunity for Hawai'i. PMID- 27563504 TI - A Treatment Planning Study of Stereotactic Body Radiotherapy for Atrial Fibrillation. AB - PURPOSE: To explore the feasibility of using stereotactic body radiotherapy (SBRT) to irradiate the antra of the four pulmonary veins while protecting nearby critical organs, such as the esophagus. MATERIALS AND METHODS: Twenty patients who underwent radiofrequency catheter ablation for atrial fibrillation were selected. For each patient, the antra of the four pulmonary veins were identified as the target volumes on a pre-catheterization contrast or non-contrast CT scan. On each CT scan, the esophagus, trachea, heart, and total lung were delineated and the esophagus was identified as the critical organ. For each patient, three treatment plans were designed with 0, 2, and 5 mm planning margins around the targets while avoiding overlap with a planning organ at risk volume (PRV) generated by a 2 mm expansion of the esophagus. Using three non-coplanar volumetric modulated arcs (VMAT), 60 plans were created to deliver a prescription dose of 50 Gy in five fractions, following the SBRT dose regimen for central lung tumors. With greater than 97% of the planning target volumes (PTV) receiving the prescription doses, we examined dosimetry to 0.03 cc and 5 cc of the esophagus PRV volume as well as other contoured structures. RESULTS: The average PTV-0 mm, PTV-2 mm, and PTV-5 mm volumes were 3.05 +/- 1.90 cc, 14.70 +/- 5.00 cc, and 40.85 +/- 10.20 cc, respectively. With three non-coplanar VMAT arcs, the average conformality indices (ratio of prescription isodose volume to the PTV volume) for the PTV-0 mm, PTV-2 mm and PTV-5 mm were 4.81 +/- 2.0, 1.71 +/- 0.19, and 1.23 +/ 0.08, respectively. Assuming patients were treated under breath-hold with 2 mm planning margins to account for cardiac motion, all plans met esophageal PRV maximum dose limits < 50 Gy to 0.03 cc and 16 plans (80%) met < 27.5 Gy to 5 cc of the esophageal PRVs. For PTV-5 mm plans, 18 plans met the maximum dose limit < 50 Gy to 0.03 cc and only two plans met the maximum dose limit < 27.5 Gy to 5 cc of the esophageal PRV. CONCLUSIONS: The anatomical relationship between the antra of the four pulmonary veins and the esophagus varies from patient to patient. Adding 2 mm planning margins and a 2 mm PRV to the esophagus can meet the dose constraints developed for SBRT central lung tumors. Future studies are needed to validate the safety and efficacy of the planning dose, tolerance dose to normal cardiac tissue, and adequate planning margins. PMID- 27563505 TI - Spine Stereotactic Body Radiotherapy Outcomes in Patients with Concurrent Brain Metastases. AB - OBJECTIVES: Stereotactic body radiotherapy (SBRT) is an emerging technique for maximizing tumor and pain control in selected patients with spinal metastases. Outcomes for those with concurrent brain metastases (CBM) have not been well described previously. The goal of this study was to compare outcomes for patients with or without CBM treated with spine SBRT. METHODS: Records of all patients treated with SBRT for spine metastases at our institution from January 2008 to January 2014 were reviewed. Chi-square analyses and the Mann-Whitney test were used to assess the association of CBM (defined as brain metastasis present prior to or at the time of spinal SBRT) with potential covariates. The log-rank test and Cox proportional hazards regression were used to evaluate the impact of CBM on overall survival and local control from the time of the first course of spine SBRT. RESULTS: Seventy-eight patients and a total of 86 SBRT lesions were treated. Median patient age was 60 years (range: 38-84 years); 28.2% had radioresistant histologies. A single fraction was used in 91.0% of treatments. One-year local control was 89.4%, and one-year overall survival was 45.8%. A total of 19 patients (24.4%) had CBM. Among these CBM patients, 18 (94.7%) underwent intracranial radiosurgery and nine (47.4%) were diagnosed synchronously with their spine metastases. Local control was not significantly different between patients with or without CBM on univariable (median: 58 months vs. not reached, p = 0.53) or multivariable analyses (HR 0.52, 95% CI 0.06-4.33). Overall survival was also not significantly different between patients with or without CBM on univariable (median: 7 vs. 11 months, log-rank p = 0.12) or multivariable analyses (HR 1.62, 95% CI 0.87-3.03). CONCLUSIONS: Patients with CBM do not appear to have a statistically significant detriment in clinical outcomes, suggesting that CBM should not necessarily be considered a contraindication for spine SBRT. Although our study is limited by significant heterogeneity in tumor type within our series, future work should focus on the development of reliable survival prognosticators for patients undergoing spinal radiosurgery. Nearly half of the patients with CBM were diagnosed synchronously with their spine metastases, emphasizing the usefulness of obtaining a brain MRI for complete staging prior to spine SBRT. PMID- 27563506 TI - Wait Time from Suspicion to Surgery for Breast Cancer in Manitoba. AB - INTRODUCTION: Breast cancer (BC) is the most common cancer in women. The pathway for its diagnosis and treatment is relatively standardized. Nevertheless, there can be significant delays affecting the journey. The aim of this retrospective study is to describe the BC wait times (WT) from suspicion to first surgery in Manitoba and to examine factors associated with WT variability. METHODS: The cohort is composed of patients with stages I-III breast cancer who were diagnosed between September 1, 2009, and August 31, 2010, and referred to a cancer center. Patients' journeys were tracked and divided into three sequential intervals from suspicion to first diagnostic test, from first diagnostic test to diagnosis and from diagnosis to first surgery. RESULTS: Four hundred and four patients were included of whom 134 presented through the screening program. There was no difference between the study cohort and population data from the provincial Cancer Registry concerning the distribution of age, stage of cancer or residence. The median WT from suspicion to surgery was 78 days. In the screen-detected group (SD), a difference in median WT from suspicion to first diagnostic test was found for distance. This finding was first to test location, where those who travel less had longer WT than those who have longer journeys. Patients who went to centers that offer both imaging and biopsy services, even if the required test is imaging only, had to wait longer than those who went to centers that provide imaging only. SD patients needing more than one diagnostic test had a longer WT from the first test to pathological diagnosis if the first test did not include a biopsy. Patients who were seen by surgeons before final pathological diagnosis had a shorter WT from diagnosis to first surgery than those who had the surgical consult after tissue diagnosis was made. A delay to surgery was observed in the whole cohort if a plastic surgeon is required in addition to the surgical oncologist and the non-screen detected group if a radiologist is necessary. CONCLUSIONS: Variability in WT from suspicion to surgical management was found between various BC patient groups and between diagnostic centers with different types of services. The order of the provided diagnostic and surgical services may have contributed to WT. Addressing this variability by restructuring the care pathway and improving communication between different disciplines, has the potential to reduce WT. PMID- 27563507 TI - Types of Azygos Distal Anterior Cerebral Artery Branching Patterns: Relevance in Aneurysmal Surgery. AB - Azygos distal anterior cerebral artery (Az.DACA) is a rare anatomical variant. This variant has been found to be associated with aneurysms in a significant proportion of patients. We present two cases of Az.DACA aneurysms associated with this anatomical variant with different branching patterns and the corresponding technical difficulties in clipping such aneurysms. Aneurysms associated with Az.DACA present unique technical challenges in proportion to the number of branches arising near the neck and should be managed at high volume centres with the best of facilities. PMID- 27563508 TI - Propolis, A Hope for the Future in Treating Resistant Periodontal Pathogens. AB - INTRODUCTION: Periodontitis is one of the most common causes of tooth loss worldwide. Recently, special attention has been paid to natural medication for its treatment. For this purpose, propolis (bee glue) activity has also been investigated. Its antibacterial properties are mainly attributed to flavonones pinocembrin, flavonols galangin and to the caffeic acid phenethyl ester. This study is aimed at evaluating the antimicrobial effects of propolis from Pakistan on 35 clinical isolates of pigmented anaerobic periodontal pathogens. METHODS: This study was conducted in the Microbiology department, University of Health Sciences, Lahore, Pakistan. Pathogens included were Porphyromonas asaccharolytica (n=9), Porphyromonas gingivalis (n=13), Prevotella intermedia (n=9), Prevotella melaninogenica (n=4). Minimum inhibitory concentration (MIC) to three antibiotics was obtained by E-test method. All strains were sensitive to amoxicillin plus clavulanic acid and metronidazole, but 100% of P asaccharolytica and P melaninogenica strains displayed intermediate resistance to tetracycline while 69.2% P gingivalis and 100% P intermedia strains exhibited complete resistance to tetracycline. Screening for antibacterial activity of propolis extract was done by agar well diffusion assay, and all strains were found sensitive to ethanolic extract of propolis. RESULTS: MIC was obtained by agar incorporation technique with values ranging from 0.064 to 0.512 mg/ml. It was also noticed that percentage yield of ethanolic extract of propolis prepared from ultrasonic extraction method was higher compared to extract obtained with maceration. CONCLUSION: These results indicate that propolis from this region has potent antimicrobial activity against pigmented anaerobic periodontal pathogens. Taking into consideration the increasing resistance in anaerobic bacteria, this effective antimicrobial activity of propolis gives hope in the treatment of oral cavity diseases. PMID- 27563509 TI - Sibling sleep-What can it tell us about parental sleep reports in the context of autism? AB - Sleep problems are common in families raising children with Autism Spectrum Disorder (ASD). Clinicians often depend on parent reports of child sleep but minimal research exists to address the accuracy or biases in these reports. To isolate parent-report accuracy (from differences in sleep behaviors), the sleep of younger siblings were assessed within a two-group design. The present study compared parent diary reports of infant sibling sleep to videosomnography and actigraphy. In the high-risk group, families had at least one child with ASD and a younger sibling (n = 33). The low-risk comparison group had no family history of ASD (n = 42). We confirmed comparable sleep behaviors between the groups and used paired t tests, two-one-sided-tests (TOST), and Bland-Altman plots to assess parent report accuracy. The parameters of sleep onset, nighttime sleep duration, awakenings, morning rise time, and daytime sleep duration were evaluated. Diary and videosomnography estimates were comparable for nighttime sleep duration, morning rise time, and awakenings for both groups. Diary and actigraph estimates were less comparable for both groups. Daytime sleep duration estimates had the largest discrepancy with both groups reporting (on average) 40 additional minutes of sleep when compared to actigraphy estimates. In the present study, families raising children with ASD were just as accurate as other families when reporting infant sleep behaviors. Our findings have direct clinical implications and support the use of parent nighttime sleep reports. PMID- 27563510 TI - Photochemical Reactions of Aminonaphthols Caused by Laser Desorption/Ionization. AB - The formation of monomeric and dimeric ions of seven different aminonaphthols (ANLs) has been studied by using laser desorption/ionization (LDI) with a nitrogen laser. The positive-ion data of all the ANLs merely showed molecular ion M(.+) without protonated molecule [M+H](+), while 1-amino-2-naphthol (1,2-ANL) and 2-amino-1-naphthol (2,1-ANL) showed an intense dimeric ion [2 M-2H2O+H](+). The negative-ion data showed deprotonated molecule [M-H](-) in common, while the spectra of 1,2-ANL, 2,1-ANL and 8-amino-2-naphthol (8,2-ANL) accompanied an intense peak corresponding to negative molecular ion M(.-) and the 8,2-ANL and 4 amino-1-naphthol (4,1-ANL) accompanied dehydrogenated anion [M-2H](.-). The formation of monomeric ions was discussed from the standpoints of thermochemical properties such as ionization energy, gas-phase acidity, electron affinity, and bond dissociation energy. The formation of dimeric ions [2 M-2H2O+H](+) observed in the 1,2-ANL and 2,1-ANL could be explained by the radical combination in the amino groups. An isomer 5-amino-1-naphthol (1-ANL) did not give any dimeric ions in the both positive- and negative-ion spectra. The influence of laser fluence upon the appearance of the monomeric ions such as M(.+), [M+H](+), [M-H](-) and [M-2H](.-) of the 5,1-ANL has been examined. PMID- 27563511 TI - Description of full-range strain hardening behavior of steels. AB - Mathematical expression describing plastic behavior of steels allows the execution of parametric studies for many purposes. Various formulas have been developed to characterize stress strain curves of steels. However, most of those formulas failed to describe accurately the strain hardening behavior of steels in the full range which shows various distinct stages. For this purpose, a new formula is developed based on the well-known Ramberg-Osgood formula to describe the full range strain hardening behavior of steels. Test results of all the six types of steels show a three-stage strain hardening behavior. The proposed formula can describe such behavior accurately in the full range using a single expression. The parameters of the formula can be obtained directly and easily through linear regression analysis. Excellent agreements with the test data are observed for all the steels tested. Furthermore, other formulas such as Ludwigson formula, Gardner formula, UGent formula are also applied for comparison. Finally, the proposed formula is considered to have wide suitability and high accuracy for all the steels tested. PMID- 27563512 TI - On a more accurate half-discrete Hardy-Hilbert-type inequality related to the kernel of arc tangent function. AB - By means of weight functions and Hermite-Hadamard's inequality, and introducing a discrete interval variable, a more accurate half-discrete Hardy-Hilbert-type inequality related to the kernel of arc tangent function and a best possible constant factor is given, which is an extension of a published result. The equivalent forms and the operator expressions are also considered. PMID- 27563513 TI - Adjuvant FOLFOX treatment for stage III colon cancer: how many cycles are enough? AB - PURPOSE: Adjuvant FOLFOX (5-fluorouracil and oxaliplatin) chemotherapy benefits stage III colon cancer patients. However, it still results in side effects and increased cost. Reducing cycles had been thought to decrease these problems. This retrospective study aimed to find the appropriate number of treatment cycles that are sufficient for treating these patients. PATIENTS AND METHODS: A total of 213 stage III colon cancer patients receiving adjuvant FOLFOX therapy were retrospectively recruited. Demographic data were collected for analysis. Survival analyses were performed between all cases of patients receiving above and below a certain cycle number. If a significant difference was reached at that cycle number, multivariate Cox Regression was performed with those factors resulting in p < 0.2 to assess the independent prognostic factors. RESULTS: The 5-year overall survival rate of patients was 77.9 %, and the 3-year disease-free survival was 76.7 %. For overall survival, a significant benefit was noted for treatment of at least 8 cycles, for disease-free survival, significant differences were apparent from patient data of those who underwent from 7 to 12 treatment cycles. Multivariate survival analysis of that patient data at cycle 8 for overall survival and cycle 7 for disease free survival revealed cycle number as the only independent prognostic factor (p = 0.04, 0.048). CONCLUSION: Cycle number of adjuvant FOLFOX is a significant prognostic factor for stage III colon cancer patients. At least 8 cycles are needed to have an overall survival benefit, and 7 to disease-free survival. PMID- 27563514 TI - Color Doppler ultrasound morphology of glomus tumors of the extremities. AB - OBJECTIVE: The aim of this study was to investigate the value of color Doppler flow imaging (CDFI) in the diagnosis of glomus tumors in the extremities. METHODS: Sonography results of 62 nodules of 50 patients with glomus tumors in the extremities confirmed by surgery and pathology were analyzed retrospectively. RESULTS: The sex ratio in the group of 50 patients was (female:male) = 5.25:1. Glomus tumors were more common in women aged 30-40 years. 84 % (42/50) of glomus tumors occurred in the fingers, with the thumb being the most common. 2D results showed that 64.52 % (40/62) of 62 nodules were hypoechoic, 30.65 % (19/62) were heterogeneous echo, 4.84 % (3/62) were hyperechoic; 64.52 % (40/62) had a clear border, while 35.48 % (22/62) had an unclear border. CDFI showed that 38.71 % (24/62) had visible rich blood in the tumor, 35.48 % (22/62) had little visible blood in the tumor, and 25.81 % (16/62) had no significant intratumoral blood flow. Of the 50 patients, 92 % (46/50) showed a fixed contact pain, were sensitive to cold stimuli, which was improved by hot water and air, and for which anti-inflammatory treatment was ineffective. CONCLUSION: Glomus tumors in the extremities had certain ultrasound features, and its internal blood flow was diverse. Understanding this feature may be helpful for the diagnosis of non typical glomus tumors. PMID- 27563515 TI - A practical application of CP-ABE for mobile PHR system: a study on the user accountability. AB - BACKGROUND: Attribute based encryption has been widely applied for secure data protection in PHR systems. However, since different users may share the same attributes in the system, a user may leaks his private key for illegal data sharing without being detected. This will add more threat to the private data stored in PHR system. FINDING: To help users achieve higher efficiency and more secure data sharing in mobile PHR system, based on previous works, we study the traitor tracing mechanism in attribute based cryptosystem and propose a high efficient attribute based encryption with user accountability in mobile PHR system. If a malicious PHR user exposes his private key for illegal data sharing, his identity can be accurately pinpointed by the system manager. During the whole process of data sharing, no bilinear pairing operations are needed, hence this will the mobile terminal devices from heavy computation burden. CONCLUSION: As a further study, in this short report, we show that using a novel attribute based encryption with user accountability can help users achieve better efficiency and more secure data sharing in mobile PHR system. PMID- 27563516 TI - Japanese traditional dietary fungus koji Aspergillus oryzae functions as a prebiotic for Blautia coccoides through glycosylceramide: Japanese dietary fungus koji is a new prebiotic. AB - BACKGROUND: The Japanese traditional cuisine, Washoku, considered to be responsible for increased longevity among the Japanese, comprises various foods fermented with the non-pathogenic fungus Aspergillus oryzae (koji). We have recently revealed that koji contains an abundant amount of glycosylceramide. Intestinal microbes have significant effect on health. However, the effects of koji glycosylceramide on intestinal microbes have not been studied. MATERIALS AND METHODS: Glycosylceramide was extracted and purified from koji. C57BL/6N mice were fed a diet containing 1 % purified koji glycosylceramide for 1 week. Nutritional parameters and faecal lipid constituents were analyzed. The intestinal microbial flora of mice on this diet was investigated. RESULTS: Ingested koji glycosylceramide was neither digested by intestinal enzymes nor was it detected in the faeces, suggesting that koji glycosylceramide was digested by the intestinal microbial flora. Intestinal microbial flora that digested koji glycosylceramide had an increased ratio of Blautia coccoides. Stimulation of B. coccoides growth by pure koji glycosylceramide was confirmed in vitro. CONCLUSIONS: Koji functions as a prebiotic for B. coccoides through glycosylceramide. Since there are many reports of the effects of B. coccoides on health, an increase in intestinal B. coccoides by koji glycosylceramide might be the connection between Japanese cuisine, intestinal microbial flora, and longevity. PMID- 27563517 TI - The effect of Bongardia Chrysogonum on prostate tissue in a rat model of STZ induced diabetes. AB - BACKGROUND: Bongardia chrysogonum is widely used in Turkey for treating urinary tract infections and prostate hypertrophy, and it also has potent hypoglycemic effects and aids glucose homeostasis. Because of the inflammatory conditions in diabetes mellitus (DM), the prostate tissue of men with diabetes is particularly susceptible to developing hypoplasia, and DM produces characteristic pathological changes in prostate tissue. Here, we examined the effects of B. chrysogonum on the prostate tissue of rats with streptozotocin (STZ)-induced diabetes. RESULTS: The glucose levels were statistically significantly higher in the diabetic rats than in healthy controls (P < 0.001). Further, they were significantly lower in the healthy and diabetic rats administered B. chrysogonum than in the untreated diabetic rats (P < 0.001 and 0.05, respectively). The total cholesterol levels were significantly lower in the healthy rats administered B. chrysogonum than the healthy controls (P < 0.05) and diabetic rats (P < 0.01). They were also significantly lower in the diabetic rats administered B. chrysogonum than those that were left untreated (P < 0.05). The testosterone levels were significantly lower in the untreated diabetic rats than in the controls (untreated ones and those administered B. chrysogonum) and diabetic rats administered the herb (P < 0.001, 0.05 and 0.01, respectively). The oxidative stress index was significantly higher in the untreated diabetic rats than the healthy controls (P < 0.05). It was also significantly lower in the healthy and diabetic groups treated with B. chrysogonum than the untreated diabetic rats (P < 0.05). Histological examination showed no changes in the prostate tissue of the non-diabetic rats. In the diabetic group, the glandular lumens were filled with cellular debris and leucocytic infiltrate, and the glandular epithelium was degenerated and thickened. In the diabetic group treated with B. chrysogonum, the epithelium was better preserved and less debris was seen in the glandular lumen. CONCLUSION: To our knowledge, this is the first study to histologically prove the effects of B. chrysogonum on prostate tissue in diabetes. Our findings may be useful in developing B. chrysogonum into a therapeutic agent against diabetes and benign prostate hyperplasia. PMID- 27563518 TI - Fullerenes synthesis by combined resistive heating and arc discharge techniques. AB - The two main electrode techniques for fullerenes production; the direct arc technique and the resistive heating of graphite rod were employed in this work. One of the electrodes was resistively heated to high temperature and subjected to arc discharge along its length by the second graphite rod. Fullerenes solid were extracted from carbon soot samples collected from an installed arc discharge system using the solvent extraction method. The fullerenes solid obtained from carbon soot collected for 2 min of arc discharge run when one of the electrodes was resistively heated at different voltages all gave higher yields (maximum of 67 % higher, at 150 A arc current and 200 Torr chamber pressure) compared to when no resistive heating was carried out. Scanning electron microscopy and ultraviolet visible spectroscopy analysis carried out on all fullerenes solid indicated the presence of fullerenes. The enhancement of fullerenes production by combined resistive and direct arc techniques shows prospect for possible use at industrial level for large scale production. PMID- 27563519 TI - Performance analysis of CRF-based learning for processing WoT application requests expressed in natural language. AB - BACKGROUND: In this paper, we investigate the effectiveness of a CRF-based learning method for identifying necessary Web of Things (WoT) application components that would satisfy the users' requests issued in natural language. For instance, a user request such as "archive all sports breaking news" can be satisfied by composing a WoT application that consists of ESPN breaking news service and Dropbox as a storage service. FINDINGS: We built an engine that can identify the necessary application components by recognizing a main act (MA) or named entities (NEs) from a given request. We trained this engine with the descriptions of WoT applications (called recipes) that were collected from IFTTT WoT platform. IFTTT hosts over 300 WoT entities that offer thousands of functions referred to as triggers and actions. There are more than 270,000 publicly available recipes composed with those functions by real users. Therefore, the set of these recipes is well-qualified for the training of our MA and NE recognition engine. CONLUSIONS: We share our unique experience of generating the training and test set from these recipe descriptions and assess the performance of the CRF based language method. Based on the performance evaluation, we introduce further research directions. PMID- 27563520 TI - (1 + u)-Constacyclic codes over Z 4 + uZ 4. AB - Constacyclic codes are an important class of linear codes in coding theory. Many optimal linear codes are directly derived from constacyclic codes. In this paper, (1 + u)-constacyclic codes over Z 4 + uZ 4 of any length are studied. A new Gray map between Z 4 + uZ 4 and Z 4 (4) is defined. By means of this map, it is shown that the Z 4 Gray image of a (1 + u)-constacyclic code of length n over Z 4 + uZ 4 is a cyclic code over Z 4 of length 4n. Furthermore, by combining the classical Gray map between Z 4 and F 2 (2), it is shown that the binary image of a (1 + u) constacyclic code of length n over Z 4 + uZ 4 is a distance invariant binary quasi-cyclic code of index 4 and length 8n. Examples of good binary codes are constructed to illustrate the application of this class of codes. PMID- 27563521 TI - Do three years make a difference? An updated review and analysis of self initiated expatriation. AB - Self-initiated expatriates (SIEs) were initially described by Inkson et al. (J World Bus 32:351-368, 1997) as individuals who move abroad on their own volition, with personal funding, oriented towards development and career goals. After almost two decades of research, it is imperative to review the knowledge that has been developed and identify future areas of intervention. Doherty (Int J Manag Rev 15:447-469, 2013. doi:10.1111/ijmr.12005) initiated the review and this paper aims to update it and explore some unapproached aspects. Five different data bases were targeted and searched for peer-reviewed articles published in English, between 1997 and 2014, which recognized self-initiated expatriation as a distinguished form of mobility and used this terminology in the title and/or keywords list. A total of 94 articles met these inclusion criteria, 45 of which were published between 2012 and 2014. By systematically analyzing them, it was observed a surpassing growth in the number of published articles in the last 3 years. This signalizes an increase of the academic interest in studying the SIEs all over the world, involving bidirectional moves between developed and developing countries. The constructs identified by Doherty (2013) at the three different levels (micro, meso and macro) continued to be explored, using qualitative or quantitative approaches. Besides this, a multi-informant approach has been adopted in some studies, while others focused on concept clarification, taking into consideration some of Doherty's (2013) suggestions for future research. Three years of research made an enormous contribution to the development of knowledge about SIEs, but some aspects can be further explored; hence they are identified and thoroughly discussed. PMID- 27563522 TI - Solutions to some congruence equations via suborbital graphs. AB - We relate the connection between the sizes of circuits in suborbital graph for the normalizer of [Formula: see text] in PSL(2,[Formula: see text]) and the congruence equations arising from related group action. We give a number theoretic result which says that all prime divisors of [Formula: see text] for any integer u must be congruent to [Formula: see text]. PMID- 27563523 TI - On an open question of V. Colao and G. Marino presented in the paper "Krasnoselskii-Mann method for non-self mappings". AB - Let H be a Hilbert space and let C be a closed convex nonempty subset of H and [Formula: see text] a non-self nonexpansive mapping. A map [Formula: see text] defined by [Formula: see text]. Then, for a fixed [Formula: see text] and for [Formula: see text], Krasnoselskii-Mann algorithm is defined by [Formula: see text] where [Formula: see text]. Recently, Colao and Marino (Fixed Point Theory Appl 2015:39, 2015) have proved both weak and strong convergence theorems when C is a strictly convex set and T is an inward mapping. Meanwhile, they proposed a open question for a countable family of non-self nonexpansive mappings. In this article, authors will give an answer and will prove the further generalized results with the examples to support them. PMID- 27563524 TI - Hospital acquired Clostridium difficile infection in pediatric wards: a retrospective case-control study. AB - BACKGROUND: Clostridium difficile is a major cause of antibiotic-associated diarrhea and frequently results in healthcare-associated infections. The aim of this study was to determine the incidence and potential risk factors for C. difficile infection (CDI) in hospitalized children who developed diarrhea. A retrospective study was performed at a university hospital in Istanbul over a three-year period (2012-2014). RESULTS: During the study period 12,196 children were hospitalized, among them 986 (8 %) children with diarrhea were investigated for CDI and 100 (0.8 %) children were diagnosed with CDI. The incidence of CDI in hospitalized children was 4/1000, 9/1000 and 9/1000 patients per year in year 2012, 2013 and 2014, respectively (p = 0.008, p < 0.01). The mean age of children with CDI (2.6 +/- 2.6 months) was lower than children without CDI (57.5 +/- 63.5 months) [p = 0.001]. In the multivariate analysis, the presence of underlying chronic diseases [presence of malnutrition (OR 7, 95 % CI 1.33-36.7, p = 0.021), presence of solid organ tumors (OR 6, 95 % CI 2.4-15.7, p < 0.00), presence of congenital heart diseases (OR 4.6, 95 % CI 1.13-18.7, p = 0.03), hospitalization in PICU (OR 15.6, 95 % CI 3.2-75.8, p = 0.001) and hospitalization in hematology and oncology ward (OR 7.8, 95 % CI 2-29.9, p = 0.002)] were found to be independent risk factors for CDI. CONCLUSION: This is the first description of the incidence and associated risk factors of CDI in Turkish children. One of the most important risk factor was prior antibiotic exposure which emphasizes the importance of antibiotic stewardship programs. PMID- 27563527 TI - The analysis of a reactive hydromagnetic internal heat generating poiseuille fluid flow through a channel. AB - In this paper, the analysis of a reactive hydromagnetic Poiseuille fluid flow under different chemical kinetics through a channel in the presence of a heat source is carried out. An exothermic reaction is assumed while the concentration of the material is neglected. The Adomian decomposition method together with Pade approximation technique are used to obtain the solutions of the governing nonlinear non-dimensional differential equations. Effects of various physical parameters on the velocity and temperature fields of the fluid flow are investigated. The entropy generation analysis, irreversibility distribution ratio, Bejan number and the conditions for thermal criticality for different chemical kinetics are also presented. PMID- 27563526 TI - Incidence and risk factors of urinary incontinence in women visiting Family Health Centers. AB - BACKGROUND: The objective of this study is to determine the incidence and the risk factors of the urinary incontinence in women visiting the Health Family Center. METHODS: 430 women, who visited three Family Health Centers in the city center of Erzurum for any reason between 25 November and 20 January 2016, were included in this study without any sampling. The data were collected by using the face-to-face interview method. Percentage distribution, Chi square test, and logistic regression analysis were used in order to analyze the data. RESULTS: It was determined that 37.2 % of these women had urinary incontinence, but only 29.3 % of them visited a physician because of this complaint. Among a total of 160 women with urinary incontinence findings, stress type incontinence was observed at the highest rate (33.7 %), which was followed by mixed type (31.8 %), urge type (20.6 %) and other types (overflow, continuous urinary incontinence) (13.7 %). It was found that urinary incontinence had a significant correlation with the number of children, genital prolapse, duration of delivery longer than 24 h, diabetes and urogenital infection, but not with the age at the first and last childbirth, presence of the episiotomy, birth weight over 4 kg, and smoking. CONCLUSIONS: It was determined that one-third of the women had urinary incontinence and certain medical and obstetric conditions were affecting the development of urinary incontinence. It is thought that it is important for the healthcare personnel to take the progression of the urinary incontinence under control by preventing the risk factors and to encourage the patients to seek treatment with the help of the proper information indicating that urinary incontinence is a treatable and preventable condition. PMID- 27563525 TI - Prevalence of sensitization to food allergens and challenge proven food allergy in patients visiting allergy centers in Rawalpindi and Islamabad, Pakistan. AB - In this study, we estimated the prevalence of food allergy in the adult allergic patients of Rawalpindi and Islamabad , Pakistan, based on self-report, skin prick test (SPT) and oral food challenge test (OFC). SPT was used for the estimation of sensitization to wheat, egg, milk, beef, chicken, mutton, fish, corn, lentils, rice, soya, peanut and banana. Among 689 patients, 39.19 % showed sensitivity to one or more foods, where, sensitization to wheat (156; 22.6 %) was highest, followed by egg (148; 21.48 %) and milk (138; 20.03 %). Sensitization to various proteins ranged between 15.53-15.97 %, while lentils, corn, rice, soya and peanut sensitization was 15.4, 16, 12.5, 12 and 11.5 % respectively. Only 7.1 % patients were SPT positive for banana allergen. SPT was performed in patients with self reported food allergy (341/689) and also with no self-reported history of food allergy (348/689). SPT results were positive in 69.8 % of the self-report group, whereas, in the patients with no self-reported food allergy 9.2 % were found sensitized to one or more tested food allergens. 101 patients were recruited for OFC, 61 % of these were confirmed of food allergy. The prevalence of food allergy in the study population was 9 %. Food specific OFC results show that wheat allergy is affecting 1.6 % (95 % CI 0.9-2.84 %) of the total allergy patients, followed by egg allergy 1.31 % (95 % CI 0.70-2.47 %). Furthermore, corn allergy, rice allergy and peanut allergy were 1.02, 0.87 and 0.73 %, respectively. In conclusion, wheat allergy is the most prevalent, followed by egg, chicken, beef and fish allergy, respectively. PMID- 27563528 TI - Predictors of doping intentions, susceptibility, and behaviour of elite athletes: a meta-analytic review. AB - Research in doping has focused on potential intervention strategies, increasingly targeting predicting factors. Yet, findings are inconsistent, mostly athlete centred and explain only limited variances in behaviour. This critical review aims to (a) summarize studies that identified predictors of doping intentions, susceptibility, and behaviour in elite athletes and to (b) analyse in how far previous research included aspects beyond athlete-centred approaches, such as context and sporting culture. We reviewed 14 studies that focused on elite athletes. Situational temptation, attitudes, and subjective norms seem to be strong predicting variables of doping intentions (r >= 0.50), but intention was no predictor for behaviour. Attitudes were a significant predictor for both, doping susceptibility (r = 0.47) and behaviour (r = 0.30). Most of the predictors are athlete-centred and ignore macro-level factors that might help to explain how certain individual traits impact on the decision making process. The findings from this review call for a critical discussion of whether current doping prevention research needs to take new directions. We propose future research to bridge findings of psychologists and sociologists, as it appears that doping behaviour cannot be explained by ignoring the one or the other. Impacts of sporting culture that have been identified in qualitative approaches need to be integrated in future quantitative approaches to test for its external validity. Inclusion of both, micro- and macro level factors may enable an integrative prevention program that creates a sporting culture without doping. PMID- 27563529 TI - Prenatal diagnosis of a variant of the azygos venous system. AB - BACKGROUND: The azygos venous system consists of the azygos vein on the right side and the hemiazygos and accessory hemiazygos on the left side. The azygos vein runs through the abdominal cavity along the right side of the vertebral bodies, in a cranial direction, passes through the diaphragm and reaches the mediastinum, where it forms the arch of the azygos which flows into the superior vena cava. Along its course, the azygos vein communicates with the intercostal veins on the right, the hemiazygos vein that collects blood from the left lower intercostal veins, and accessory hemiazygos vein that drains into the left upper intercostal veins. The last two, at the level of the seventh thoracic vertebra, unite and end in the azygos vein. The accessory hemiazygos vein is normally included in the length between T4 and T8. The embryological origin of the accessory hemiazygos vein is the result of an expansion in the direction of the cranial hemiazygos vein, which comes from the left upper sovracardinale vein (Dudiak et al. in Semin Roentgenol 24(1):47-55, 1989; Radiographics 11(2):233 246, 1991; Webb et al. in Am J Roentgenol 139(1):157-161, 1982). FINDINGS: This case report describes a rare variant of azygos vein system identified in prenatal diagnosis and confirmed by postnatal ultrasonography. CONCLUSIONS: The observation of the patient has excluded hemodynamic alterations associated with vascular anomaly. PMID- 27563530 TI - Maxilla-nasion-mandible (MNM) angle: an indicator to assess fetal facial profile in first-trimester of pregnancy. AB - OBJECTIVE: The aim of this study was to observe whether there existed significant differences in the maxilla-nasion-mandible angle (MNM) between the first- and second-trimester of pregnancy, and to observe its predictive values for trisomy 18. METHODS: Two experienced ultrasonologists used 2D and 3D ultrasound imaging techniques to obtain the facial sagittal sections of fetuses in the first trimester of pregnancy (crown-rump length 45-84 mm), respectively, so as to measure MNM. RESULTS: MNM could be measured in 91 % of normal fetuses, and the measurement differences by different operators in different groups were <1.1 degrees ; average MNM was 11.0 degrees , and no significant change was observed in different gestational ages (P = 0.15). The average of MNMs in fetuses with trisomy 18 was 16.6 degrees , which were all higher than the 95th percentile of normal measurement data. The sensitivity and specificity of increased MNM on the abnormal detection of trisomy 18 were 54.7 and 97.4 %, respectively. CONCLUSIONS: The feasibility and reproducibility of measuring MNM in early pregnancy were good. MNM had certain suggestive roles for aneusomic chromosomal abnormalities, especially for fetuses with trisomy 18. PMID- 27563531 TI - Multiperiod Maximum Loss is time unit invariant. AB - Time unit invariance is introduced as an additional requirement for multiperiod risk measures: for a constant portfolio under an i.i.d. risk factor process, the multiperiod risk should equal the one period risk of the aggregated loss, for an appropriate choice of parameters and independent of the portfolio and its distribution. Multiperiod Maximum Loss over a sequence of Kullback-Leibler balls is time unit invariant. This is also the case for the entropic risk measure. On the other hand, multiperiod Value at Risk and multiperiod Expected Shortfall are not time unit invariant. PMID- 27563532 TI - Timely stereotactic body radiotherapy (SBRT) for spine metastases using a rapidly deployable automated planning algorithm. AB - PURPOSE/OBJECTIVES: The complex planning and quality assurance required for spine SBRT are a barrier to implementation in time-sensitive or limited resource clinical situations. We developed and validated an automated inverse planning algorithm designed to streamline planning and allow rapid delivery of conformal single fraction spine SBRT using widely available technology. MATERIALS/METHODS: The Rapid Spine (RaSp) automated script successfully generated single fraction SBRT plans for fourteen complex spinal lesions previously treated at a single high-volume institution. Automated RaSp plans were limited to 5 beams with a total of 15 segments (allowing calculation-based verification) and optimized based on RTOG 0631 objectives. Standard single fraction (16 Gy) stereotactic IMRT plans were generated for the same set of complex spinal lesions and used for comparison. A conservative 2 mm posterior isocenter shift was used to simulate minor set-up error. RESULTS: Automated plans were generated in under 5 min from target definition and had a mean dose to the PTV of 1663 cGy (SD 131.5), a dose to 90 % of PTV (D90) of 1358 cGy (SD 111.0), and a maximum point dose (Dmax) to the PTV of 2055 cGy (SD 195.2) on average. IMRT plans took longer to generate but yielded more favorable dose escalation with a mean dose to the PTV of 1891 cGy (SD 117.6), D90 of 1731 cGy (SD 126.5), and Dmax of 2218 cGy (SD 195.7). A 2 mm posterior shift resulted in a 20 % (SD 10.5 %) increase in cord dose for IMRT plans and a 10 % (SD 5.3 %) increase for RaSp plans. The 2 mm perturbation caused 3 cord dose violations for the IMRT plans and 1 violation for corresponding RaSp plans. CONCLUSION: The Rapid Spine plan method yields timely and dosimetrically reasonable SBRT plans which meet RTOG 0631 objectives and are suitable for rapid yet robust pretreatment quality assurance followed by expedited treatment delivery. RaSp plans reduce the tradeoff between rapid treatment and optimal dosimetry in urgent cases and limited resource situations. PMID- 27563533 TI - Influenza-like illness outbreaks in nursing homes in Corsica, France, 2014-2015: epidemiological and molecular characterization. AB - BACKGROUND: To study the molecular epidemiology of the influenza outbreaks in nursing homes (NHs) to determine whether multiple influenza strains were involved. METHODS: From September to December 2014, NHs in Corsica were invited to participate in an ongoing daily epidemiological and microbiological surveillance for influenza-like illness (ILI) among residents and health care workers (HCWs). RESULTS: The study involved 12 NHs. Respiratory illness meeting the ILI case definition was observed among 44 residents from whom 22 specimens were collected. Of the 22 residents with a nasopharyngeal sample, 13 (59 %) were positive for at least one of the 11 pathogens analysed. Among these 13 patients, 11 (92 %) presented a confirmed influenza (A/H3N2) and two had another respiratory virus: one human metapneumovirus and one human coronavirus. Of patients with a confirmed influenza A(H3N2), 10 (91 %) were vaccinated against influenza during the 2014-2015 season. Two influenza outbreaks were reported in two NHs, caused by influenza A(H3N2) strains belonging to cluster 3C.3 and 3C.2a. Although antivirals were available, prophylaxis was not used. CONCLUSIONS: Phylogenetic analysis seems to suggest no multiple introduction into the two NHs reporting the two influenza A(H3N2) outbreaks. A number of factors could have contributed to transmitting influenza in NHs including, the absence of administration of antiviral treatment for prophylaxis of all residents/staff regardless of immunization status because of the poor vaccine match during each outbreak, the intensive contacts with incompletely protected residents and HCWs, and the low adherence of NHs to notification of ILI outbreaks to the health authorities. PMID- 27563534 TI - Multiple Meningiomas in a Patient with Cowden Syndrome. AB - BACKGROUND: Cowden syndrome is a rare, multisystem disease manifesting with increased hamartomas and neoplasms. Though meningioma has been documented in patients with Cowden syndrome, the relationship between these two phenomena is still unclear. CASE DESCRIPTION: We report a case of a 43-year-old female patient with a known PTEN mutation and clinical history of Cowden syndrome. A workup of headache demonstrated two skull base meningiomas. At the time of surgery, several additional tiny meningiomas were detected in the same region. CONCLUSIONS: The development of multiple meningiomas in a patient with predisposition for tumor is more than coincidental. Though PTEN mutations and deletions have not been shown to be critical for meningioma development, this case challenges that conclusion. In light of recent genetic advances in meningioma molecular pathogenesis, the role of the PTEN/AKT/PI3K pathway is discussed. PMID- 27563535 TI - Potential Effects on Cardiorespiratory and Metabolic Status After a Concurrent Strength and Endurance Training Program in Diabetes Patients - a Randomized Controlled Trial. AB - BACKGROUND: Concurrent aerobic and resistance training (CART) programs have been widely recommended as an important strategy to improve physiologic and functional performance in patients with chronic diseases. However, the impact of a personalized CART program in patients with type 2 diabetes (T2D) requires investigation. Therefore, the primary aim of the current study is to investigate the impact of CART programs on metabolic profile, glycemic control, and exercise capacity in patients with diabetes. METHODS: We evaluated 41 subjects with T2D (15 females and 19 males, 50.8 +/- 7 years); subjects were randomized into two groups; sedentary (SG) and CART (CART-G). CART was performed over 1.10-h sessions (30-min aerobic and 30-min resistance exercises) three times/week for 12 weeks. Body composition, biochemical analyses, peripheral muscular strength, and cardiopulmonary exercise testing were primary measurements. RESULTS: The glycated hemoglobin HbA1c (65.4 +/- 17.9 to 55.9 +/- 12.7 mmol/mol), cholesterol (198.38.1 +/- 50.3 to 186.8 +/- 35.1 mg/dl), and homeostasis model assessment insulin resistance (HOMA-IR) (6.4 +/- 6.8 to 5.0 +/- 1.4) decreased in the CART-G compared to the SG. Although body weight did not significantly change after training, skinfold measurement indicated decreased body fat in the CART-G only. CART significantly enhanced muscle strength compared to the SG (p < 0.05). CART was also associated with significant increase in peak oxygen uptake and maximal workload compared to the SG (p < 0.05). CONCLUSIONS: These data support CART as an important strategy in the treatment of patients with T2D, producing both physiologic and functional improvements. TRIAL REGISTRATION: Ensaiosclinicos.gov.br, RBR492q8z. PMID- 27563536 TI - Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape. AB - Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors" (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell's intrinsic immune defenses. RFs include nuclear proteins IFN-gamma inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID- 27563538 TI - Genotyping and pathotyping of diversified strains of infectious bronchitis viruses circulating in Egypt. AB - AIM: To characterize the circulating infectious bronchitis virus (IBV) strains in Egypt depending on the sequence of the spike-1 (S1) gene [hypervariable region-3 (HVR-3)] and to study the pathotypic features of these strains. METHODS: In this work, twenty flocks were sampled for IBV detection using RRT-PCR and isolation of IBV in specific pathogen free (SPF) chicks during the period from 2010 to 2015. Partial sequencing and phylogenetic analysis of 400 bp representing the HVR-3 of the S1 gene was conducted. Pathotypic characterization of one selected virus from each group (Egy/Var-I, Egy/Var-II and classic) was evaluated in one day old SPF chicks. The chicks were divided into 4 groups 10 birds each including the negative control group. Birds were inoculated at one day by intranasal instillation of 10(5)EID50/100 MUL of IBV viruses [IBV-EG/1212B-2012 (Egy/Var II), IBV/EG/IBV1-2011 (Egy/Var-I) and IBV-EG/11539F-2011 (classic)], while the remaining negative control group was kept uninfected. The birds were observed for clinical signs, gross lesions and virus pathogenicity. The real-time rRT-PCR test was performed for virus detection in the tissues. Histopathological examinations were evaluated in both trachea and kidneys. RESULTS: The results revealed that these viruses were separated into two distinct groups; variant (GI-23) and classic (GI-1), where 16 viruses belonged to a variant group, including 2 subdivisions [Egy/Var-I (6 isolates) and Egy/Var-II (10 isolates)] and 4 viruses clustered to the classic group (Mass-like). IBV isolates in the variant group were grouped with other IBV strains from the Middle East. The variant subgroup (Egy/Var-I) was likely resembling the original Egyptian variant strain (Egypt/Beni-Suif/01) and the Israeli strain (IS/1494/2006). The second subgroup (Egy/Var-II) included the viruses circulating in the Middle East (Ck/EG/BSU-2 and Ck/EG/BSU-3/2011) and the Israeli strain (IS/885/00). The two variant subgroups (Egy/Var-I and Egy/Var-II) found to be highly pathogenic to SPF chicks with mortalities up to 50% than those of the classic group which was of low virulence (10% mortality). Pathogenicity indices were 25 (Egy/Var-II), 24 (Egy/Var-I) and 8 (classic); with clinical scores 3, 2 and 1 respectively. CONCLUSION: These findings indicated that the recent circulating Egyptian IBVs have multiple heterogeneous origins in marked diversifying nature of their spread, with high pathotype in specific pathogen free chicks. PMID- 27563539 TI - Surgical repair of Stanford type A aortic dissection in elderly patients: a contemporary systematic review and meta-analysis. AB - BACKGROUND: The results of surgical treatment of type A aortic dissection (AAD) in the elderly are controversial and aggravated by a higher operative mortality rate. The studies published in this subset of patients are mainly retrospective analyses or small samples from international registries. We sought to investigate this topic by conducting a contemporary meta-analysis of the most recent observational studies. METHODS: A systematic literature search was conducted for any study published in the last five years on aortic dissection treated surgically in patients 70 years and older. A pooled risk-ratio meta-analysis has been conducted three main post-operative outcomes: short-term mortality, stroke and acute kidney injury. RESULTS: A total of 11 retrospective observational studies have been included in the quantitative meta-analysis. Pooled meta analysis showed an increased risk of short term mortality for the elderly population [relative risk (RR) =2.25; 95% CI, 1.79-2.83; I (2)=0%; P<0.0001], and this has been confirmed in a sub-analysis of patients 80 years and older. The risk of having stroke (RR =1.15; 95% CI, 0.89-1.5; I (2)=0%; P=0.28) and acute kidney injury (RR =0.79; 95% CI, 0.5-1.25, I (2)=14%, P=0.31) after surgery were comparable to the younger cohort of patients. CONCLUSIONS: Although affected by an increased risk of short-term mortality in the elderly, surgical repair remains the treatment of choice for AAD. The main post-operative outcomes are comparable to younger patients and the mid-term survival rates are acceptable. PMID- 27563540 TI - Management of type A dissection with malperfusion. AB - Malperfusion is a common lethal complication of acute aortic dissection following rupture, for which the optimal management strategy has yet to be clearly established. The objective of this study was to reassess the management of acute type A aortic dissection (Type A-AAD) with malperfusion. We retrospectively analyzed the outcomes of all patients with Type A-AAD with malperfusion at the University of Michigan and compared the results from patients that directly underwent open surgical repair versus those who had percutaneous reperfusion prior to open surgical repair. Based on the results, we developed a patient care protocol for the treatment of all patients with acute type A dissection. We later re-analyzed the long-term outcomes for patients using the protocol. The present study demonstrated that, although the outcomes for patients with acute type A aortic dissection with malperfusion syndrome treated with initial percutaneous reperfusion and delayed open surgical intervention are not as good as the results for patients with uncomplicated Type A-AAD that undergo immediate surgical repair, their outcomes continue the long-term outcomes of the former group are superior. To outdo patients with acute type A aortic dissection with malperfusion syndrome treated with immediate open surgical intervention. In conclusion, at the University of Michigan we continue to use our patient care protocol to treat patients with Type A-AAD. PMID- 27563542 TI - Surgical management and outcomes of type A dissection-the Mayo Clinic experience. AB - BACKGROUND: Type A aortic dissection (TAAD) is a complex cardiovascular disease that is associated with high perioperative morbidity and mortality. The most effective approach is still being debated-such as the best cannulation technique, and conservative versus extensive initial surgery. We reviewed our experience over the last 20 years and examined for variables that correlated with observed outcomes. METHODS: All patients who underwent TAAD repair were reviewed. Chi Square tests, Fisher Exact tests and Wilcoxon tests were performed where appropriate. Survival and freedom from reoperations were analyzed with the Kaplan Meier actuarial method. RESULTS: Acute TAAD was associated with a higher incidence of permanent stroke (P=0.010), renal failure (P=0.025), prolonged mechanical ventilator support (P=0.004), higher operative mortality (P=0.039) and higher 30-day mortality (P=0.003) compared to chronic TAAD. There was a trend towards higher risk for transient neurologic events among patients who were reoperated on (P=0.057). Extensive proximal repair led to longer perfusion and cross clamp times (P<0.001) and the need for temporary mechanical support post operatively (P=0.011). More patients that had extensive distal repair underwent circulatory arrest (P=0.009) with no significant differences in the incidence of peri-operative complications, early, middle and long-term survival compared to the conservative management group. Overall survival in our series was 66.73% and 46.30% at 5 and 10 years respectively (median survival time: 9.38 years). There was a significant improvement in operative mortality (P=0.002) and 30-day mortality (P=0.033) in the second decade of our study. DISCUSSION: TAAD is a complex disease with several options for its surgical management. Each technique has its own advantages and complications and surgical management should be individualized depending on the clinical presentation. We propose our present approach to maximize benefits in both the short and long term. PMID- 27563541 TI - Evolution of surgical therapy for Stanford acute type A aortic dissection. AB - Acute type A aortic dissection (AcA-AoD) is a surgical emergency associated with very high morbidity and mortality. Unfortunately, the early outcome of emergency surgical repair has not improved substantially over the last 20 years. Many of the same debates occur repeatedly regarding operative extent and optimal conduct of the operation. The question remains: are patients suffering from too large an operation or too small? The pendulum favoring routine aortic valve resuspension, when feasible, has swung towards frequent aortic root replacement. This already aggressive approach is now being challenged with the even more extensive valve sparing aortic root replacement (V-SARR) in selected patients. Distally, open replacement of most of the transverse arch is best in most patients. The need for late aortic re-intervention has not been shown to be affected by more extensive distal operative procedures, but the contemporary enthusiasm for a distal frozen elephant trunk (FET) only seems to build. It must be remembered that the first and foremost goal of the operation is to have an operative survivor; additional measures to reduce late morbidity are secondary aspirations. With increasing experience, true contraindications to emergency surgical operation have dwindled, but patients with advanced age, multiple comorbidities, and major neurological deficits do not fare well. The endovascular revolution, moreover, has spawned innovative options for modern practice, including ascending stent graft and adaptations of the old flap fenestration technique. Despite the increasingly complex operations and ever expanding therapies, this life-threatening disease remains a stubborn challenge for all cardiovascular surgeons. Development of specialized thoracic aortic teams and regionalization of care for patients with AcA-AoD offers the most promise to improve overall results. PMID- 27563543 TI - Is the outcome in acute aortic dissection type A influenced by of femoral versus central cannulation? AB - BACKGROUND: The purpose of this study was to evaluate the single-center experience in initial femoral versus central cannulation of the extracorporeal circulation for acute aortic dissection type A (AADA). METHODS: Between January 2003 and December 2015, 235 patients underwent repair of AADA. All patients were evaluated for the type of arterial cannulation (femoral vs. central) for initial bypass. Demographic data and outcome parameters were accessed. RESULTS: One hundred and twenty seven (54.0%) were initially cannulated in the central aortic vessels (ascending aorta or subclavian/axillary artery) and 108 (46.0%) in the femoral artery. Patients were comparable between age (62.4+/-14.4 vs. 62.9+/-14.4 years, P=0.805), gender (male, 62.2 vs. 69.4%, P=0.152) and previous sternotomy (15.7 vs. 16.7%, P=0.861) between both cannulation groups; while EuroSCORE I (11.5+/-4.0 vs. 12.7+/-4.2, P=0.031) and ASA Score (3.5+/-0.81 vs. 3.8+/-0.57, P=0.011) were significantly higher in the femoral artery cannulation group. Bypass (249+/-102 vs. 240+/-81 min, P=0.474), X-clamp (166+/-85 vs. 157+/-67 min, P=0.418) and circulatory arrest time (51.6+/-28.7 vs. 48.3+/-21.7 min, P=0.365) were similar between the groups as were lowest temperature (18.1+/-2.0 vs. 18.1+/ 2.2, P=0.775). Postoperative neurologic deficit and 30-day mortality were comparable between both cannulation groups (11.7 vs. 7.2%, P=0.449 and 20.2 vs. 16.9%, P=0.699, central vs. peripheral cannulation). Multivariate analysis revealed only EuroScore I above 13 as single preoperative predictor for mortality. CONCLUSIONS: AADA can be operated with both femoral and central cannulation with similar results. Risk for early mortality was driven by the preoperative clinical and hemodynamic status before operation rather than the cannulation technique. PMID- 27563544 TI - Outcomes and management of type A intramural hematoma. AB - BACKGROUND: Initial optimal management of acute type A aortic dissection (ATAAD) with intramural hematoma (ATAIMH) remains controversial, especially between centers in the Eastern vs. Western worlds. We examined the literature and our experience to report outcomes after repair of ATAIMH. METHODS: We reviewed the hospital, follow-up clinic records and online mortality databases for all patients who presented to our center for open repair of ATAAD between 1999 and 2014. Preoperative characteristics, early and long-term outcomes were compared between classic ATAAD vs. ATAIMH. Survival was analyzed using Kaplan-Meier and log-rank statistics. RESULTS: Of the 523 repaired ATAAD, 101 patients (19%) presented with IMH and 422 (81%) had classic dissection. ATAIMH were significantly older (64.8+/-12.9 vs. 56.8+/-14.6 years; P<0.001), more commonly females (39% vs. 26%; P=0.010), had poor baseline renal function (i.e., glomerular filtration rate) (P<0.017), more retrograde dissections (27% vs. 8.3%; P<0.001), and less distal malperfusion (5% vs. 15%; P<0.001). Age greater than 60 years, female sex, retrograde dissection, and Marfan syndrome were strongly correlated with ATAIMH. Time to repair for ATAIMH was longer (median, 55.3 vs. 9.8 hours; P<0.001) with one death in ATAIMH within three days of presentation (0.9% vs. 6%; P=0.040). In all, 30-day mortality in ATAIMH was not different from classic ATAAD (12% vs.16%; P=0.289). A significantly lower incidence of postoperative dialysis in ATAIMH was noted (10% vs. 19%; P=0.034). When adjusted for age and renal function, late survival was improved with IMH (P<0.039). CONCLUSIONS: ATAIMH continues to be associated with significant morbidity and mortality, comparable to classic aortic dissection. A multidisciplinary management approach involving aggressive medical management and risk stratification for timely surgical intervention, along with genetic profiling, is recommended for optimal care. Long-term monitoring is mandatory to assess compliance to medical therapy and recognition of evolving complications. PMID- 27563545 TI - Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection. AB - BACKGROUND: The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. METHODS: A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. RESULTS: Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102-0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962-1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). CONCLUSIONS: During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection. PMID- 27563537 TI - Microbiology laboratory and the management of mother-child varicella-zoster virus infection. AB - Varicella-zoster virus, which is responsible for varicella (chickenpox) and herpes zoster (shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella (particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times: (1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection; (2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear (atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation; (3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and (4) when the baby is born and it is necessary to confirm a diagnosis of varicella (and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn. PMID- 27563546 TI - Associated bare stenting of distal aorta with a Djumbodis((r)) system versus conventional surgery in type A aortic dissection. AB - BACKGROUND: The effectiveness of additional stenting of the distal aorta as compared to conventional surgery alone in type A aortic dissection (TAD) has yet to be proven. METHODS: We conducted this multicenter comparative study to evaluate the effects of antegrade bare stenting of the dissected aorta beyond the distal anastomosis with a Djumbodis((r)) device system (DDS). Outcomes that were measured included early outcomes, overall mortality from aortic cause and late aortic events including re-interventions. A consecutive series of 134 patients operated on in two participating centers were distributed into study and control groups according to the treatment received: conventional surgery with DDS (DJ group, n=42) or without (control group, n=92). RESULTS: Operative mortality was 21.4% and 17.6% in the DJ and control groups, respectively (P=0.9), and was within pre-specified alarm lines for both groups. In multivariate analysis, the only independent predictor of operative mortality was the presence of any complication (cardiac tamponade or malperfusion, P=0.05), which occurred more in the DJ group (OR =1.3; non-significant). Sixty patients were included into the matched survivors cohorts study (propensity scoring). The aortic event-free survival at 7 years for early survivors was 77%+/-10% and 48%+/-11% in the matched DJ group and control group, respectively (HR =0.66). Late mortality from an aortic cause was 10% and 20% in the matched DJ group and control group, respectively (RR =0.5). Actuarial freedom from aortic or vascular interventions was 71%+/-10% and 67%+/-9% in the matched DJ and control group, respectively. Operative mortality was not influenced by the use of DDS as compared to conventional surgery alone for TAD. CONCLUSIONS: We observed a trend towards better organ perfusion in the DJ group postoperatively, and more aortic events and deaths of aortic cause in the control group during follow-up. PMID- 27563547 TI - IRAD experience on surgical type A acute dissection patients: results and predictors of mortality. AB - Type A acute aortic dissection (TAAD) is a disease that has a catastrophic impact on a patient's life and emergent surgery represents a key goal of early treatment. Despite continuous improvements in imaging techniques, medical therapy and surgical management, early mortality in patients undergoing TAAD repair still remains high, ranging from 17% to 26%. In this setting, the International Registry of Acute Aortic Dissection (IRAD), the largest worldwide registry for acute aortic dissection, was established to assess clinical characteristics, management and outcomes of TAAD patients. The present review aimed to evaluate and comment on outcomes of TAAD surgery as reported from IRAD series. PMID- 27563548 TI - Differential aspects of ascending thoracic aortic dissection and its treatment: the North American experience. AB - Acute type A aortic dissection is a deadly disease with significant morbidity and mortality. We describe the differential aspects of the disease and the North American experience with its treatment. PMID- 27563549 TI - Differential aspects of the disease and treatment of Thoracic Acute Aortic Dissection (TAAD)-the European experience. AB - The management of patients with acute aortic dissection continues to be a challenge. It is an uncommon but lethal condition which continues to be under diagnosed and under-treated. In this review, the term acute aortic syndrome is preferred in order to embrace the closely related pathologies of intramural hematoma (IMH) and penetrating aortic ulcer (PAU). PMID- 27563550 TI - Current surgical results of acute type A aortic dissection in Japan. AB - Current surgical results of acute type A aortic dissection in Japan are presented. According to the annual survey by the Japanese Association of Thoracic Surgery, 4,444 patients with acute type A aortic dissection underwent surgical procedures and the overall hospital mortality was 9.1% in 2013. The prevalence of aortic root replacement with a valve sparing technique, total arch replacement (TAR), and frozen stent graft are presented and strategies for thrombosed dissection or organ malperfusion syndrome secondary to acute aortic dissection are discussed. PMID- 27563551 TI - When and how to replace the aortic root in type A aortic dissection. AB - Management of aortic root pathology during repair of acute type A aortic dissection (TAAD) requires a comprehensive evaluation of the patient's anatomy, demographics, comorbidities and physiologic status at the time of emergent operative intervention. Surgical options include conservative repair of the root (CRR) (with or without replacement of the aortic valve), replacement of the native valve and aortic root using a composite valve-conduit and valve sparing root replacement (VSRR). The primary objective of this review is to provide data for surgeons to aid in their decision-making process regarding management of the aortic root during repair of TAAD. No time or language restrictions were imposed and references of the selected studies were checked for additional relevant citations. Multiple retrospective reviews have demonstrated equivalent operative mortality between aortic root repair and replacement during TAAD. There is a higher incidence of aortic root reintervention with aortic root repair compared to aortic root replacement (ARR). Experienced, high-volume aortic centers have demonstrated the safety of VSRR in young, hemodynamically stable patients presenting with TAAD. In conclusion, aortic root repair can safely be performed in the vast majority of patients with TAAD. Despite the increased surgical complexity, ARR does not increase operative mortality and improves the freedom from root reintervention. VSRR can be performed in highly selected populations of patients with TAAD with durable mid-term valve function. PMID- 27563552 TI - When and how to replace the aortic arch for type A dissection. AB - Acute type A aortic dissection (AAAD) remains one of the most challenging diseases in cardiothoracic surgery and despite numerous innovations in medical and surgical management, early mortality remains high. The standard treatment of AAAD requires emergency surgery of the proximal aorta, preventing rupture and consequent cardiac tamponade. Resection of the primary intimal tear and repair of the aortic root and aortic valve are well-established surgical principles. However, the dissection in the aortic arch and descending untreated aorta remains. This injury is associated with the risk of subsequent false lumen dilatation potentially progressing to rupture, true lumen compression and distal malperfusion. Additionally, the dilatation of the aortic arch, the presence of a tear and retrograde dissection can all be considered indication for a total arch replacement in AAAD. In such cases a more aggressive strategy may be used, from the classic aortic arch operation to a single stage frozen elephant trunk (FET) technique or a two-stage approach such as the classical elephant trunk (ET) or the recent Lupiae technique. Although these are all feasible solutions, they are also complex and time demanding techniques requiring experience and expertise, with an in the length of cardiopulmonary bypass and both myocardial and visceral ischemia. Effective methods of cerebral, myocardial as well visceral protection are necessary to obtain acceptable results in terms of hospital mortality and morbidity. Moreover, a correct assessment of the anatomy of the dissection, through the preoperative angio CT scan, in addition to the clinical condition of the patients, remain the decision points for the best arch repair strategy to use in AAAD. PMID- 27563553 TI - Thoracic endovascular repair for acute type A aortic dissection: operative technique. AB - Acute type A aortic dissection is a potentially lethal condition which requires immediate diagnostic and therapeutic intervention. Open surgical repair remains the standard of care as survival rates continue to improve in the modern surgical era. Unfortunately, up to twenty percent of patients are denied surgical therapy because they are deemed medically unfit to undergo open repair. The application of thoracic endovascular aortic repair (TEVAR) has changed the treatment paradigm for aortic disease involving the descending thoracic aorta and may be a viable rescue option for patients with type A dissection who are not eligible for open surgical repair. New endovascular devices and advanced image-guided procedures are continually evolving. This article summarizes the pathology of aortic dissection and focuses on currently available endovascular solutions for transapical and transfemoral stent graft deployment for acute aortic dissection involving the ascending aorta for selected patients who are ineligible for open surgical repair. PMID- 27563554 TI - Valve sparing-aortic root replacement with the reimplantation technique in acute type A aortic dissection. PMID- 27563555 TI - The direct aortic cannulation for acute type A aortic dissection. PMID- 27563556 TI - Aortic valve reimplantation using Kuban Cuff modification in a patient with acute type A aortic dissection and aortic valve insufficiency. PMID- 27563557 TI - Thoracic aortic aneurysm. PMID- 27563558 TI - Breast reconstruction after mastectomy: does it decrease depression at the long term? AB - BACKGROUND: Depression is associated with breast cancer survivors in 22%. Although breast reconstruction (BR) is intended to provide psychological improvements such as reducing depression, literature is inconclusive and without long-term follow-up. The objective is to evaluate the impact of BR after breast cancer related mastectomy on the long-term depression risk and assess predictive factors for depression. METHODS: Women who underwent a curative mastectomy between 1999 and 2009 were included. After a mean follow-up of more than 6 years after operation, the Beck Depression Inventory-13 (BDI-13) evaluated depressive symptoms. Multivariable regression analysis provided predictors for depression. RESULTS: A total of 139 patients, 34 (24.5%) with and 105 (75.5%) without BR, were analyzed. Seventy-seven patients (48.2%) were at high risk for mild (n=58), moderate (n=5) or severe (n=4) depression. There was a trend for slightly better BDI-13 outcomes for women who underwent BR (2 vs. 4; P=0.06). Living alone [odds ratio (OR): 2.16; P=0.04], low educational level (OR: 3.70; P<0.01) and adjuvant hormonal/endocrine-therapy (OR: 2.36; P=0.02) were associated with an increased depression risk. CONCLUSIONS: BR has no clear influence on depressive symptoms on the long-term. Predictive factors should alert clinicians to assess depressive symptoms in specific breast cancer patients during follow-up. PMID- 27563559 TI - Factors associated with patients in the Scottish Highlands who chose mastectomy when suitable for breast conservation. AB - BACKGROUND: Despite being suitable for breast conservation surgery (BCS) a proportion of women choose mastectomy. This study aimed to assess the pre operative pathological and geographic factors associated with choosing mastectomy rather than BCS in a single centre that serves a large geographical area encompassing urban, rural and remote island populations. METHODS: A retrospective analysis of all patients suitable for BCS between January 2011 and December 2013 was undertaken. Pre-operative pathological features were compared using the Pearson chi squared test as was distance to the treatment centre from the patient's home. A questionnaire was sent to all those who chose mastectomy to identify the factors that influenced their decision. RESULTS: A total of 446 patients suitable for BCS were identified of which 46 (11%) chose to undergo mastectomy. Patients choosing mastectomy were more likely to present symptomatically (P=0.009), have tumours larger than 20 mm at diagnostic imaging (P=0.001) and have positive axillary staging (P=0.004). Patients choosing mastectomy were more likely to live remotely (P=0.051). Those patients who chose mastectomy felt this gave a better long-term outcome (18 patients, 44%) and peace of mind (14 patients, 34%). CONCLUSIONS: Adverse pre-operative pathological features were associated with patients choosing mastectomy rather than BCS. There was a trend for patients who chose mastectomy to live remotely from the treatment centre. Patients choosing mastectomy most commonly cited a better long-term outcome and peace of mind as the reason behind their decision. Understanding what influences a patient's surgical choice will allow clinicians and patients to engage in a fully informed pre-operative decision making process. PMID- 27563560 TI - Circumcision with Glubran((r)) 2 in children: experience of Italian Center. AB - BACKGROUND: Circumcision is one of the most common surgical procedures in the world. Despite it is known its wide prevalence for religious and medical reasons in children, it remains a controversial practice in paediatric age. To date, there is no described the gold standard technique to circumcise paediatric patients. We started to use glue for circumcision about 2 years ago. We designed this prospective study with the aim to compare two surgical techniques, which were used in our hospital to perform circumcision in children. The implication for practice was the understanding if there were differences between these approaches related to patient's and parents benefits to manage this condition and benefits for surgeon and hospital in term of saving money and time. METHODS: This is a randomized, single-blind one-center study. It was conducted at the Department of Paediatric Surgery of Siena. Data were collected between March 2011 and December 2012. Study's population involved all patients who required circumcision. Two randomizes groups: group one which involved patients who underwent circumcision using sutures and group two, which involved patients who underwent circumcision using surgical glue (Glubran((r)) 2). Two exclusion criteria were used: the redo-circumcision and the allergy or hyper-sensibility to cyanoacrylate (main component of glue). RESULTS: We report 99 patients who underwent circumcision with Glubran((r)) 2 in comparison with a group of children circumcised with sutures (vycril rapide). We measured three outcomes (operating time, postoperative pain and assessment of cosmetic), which, even if not all statistically significant, allowed us to draw any conclusions about the use of glue in circumcision. CONCLUSIONS: Traditional circumcision is performed using a standard sleeve technique with sutures for the approximation of the skin edges. However, since some years a tissue adhesive as N-butyl-2-cyanoacrylate (NBCA) (Glubran((r)) 2) is used in many centers to circumcise children. Based on our results we can conclude that, glue (Glubran((r)) 2) application is an excellent alternative to circumcision in paediatric age for a faster surgery, less postoperative pain and good early cosmetic. PMID- 27563561 TI - Are there disparities in the presentation, treatment and outcomes of patients diagnosed with medullary thyroid cancer?-An analysis of 634 patients from the California Cancer Registry. AB - BACKGROUND: Race, gender and socioeconomic disparities have been suggested to adversely influence stage at presentation, treatment options and outcomes in patients with cancer. Underserved minorities and those with a low socioeconomic status (SES) present with more advanced disease and have worse outcomes for differentiated thyroid cancer, but this relationship has never been evaluated for medullary thyroid cancer (MTC). METHODS: We used the California Cancer Registry (CCR) to evaluate disparities in the presentation, treatment and outcomes of patients diagnosed with MTC. RESULTS: We identified 634 patients with MTC diagnosed between 1988 and 2011. Almost everyone (85%) underwent thyroidectomy with 50% having a central lymph node dissection (CLND). There were no statistically significant differences by age, race or SES in mean tumor size or the proportion of patients diagnosed with localized disease, but men were diagnosed with larger tumors than women and were less likely to be diagnosed at a localized stage. Younger patients and women were more likely to be treated with a thyroidectomy. There were no statistically significant differences in surgical treatment by race or SES. Patients in the highest SES category had a better overall survival, but not disease specific survival, than those in the lowest SES (HR =0.3, CI =0.1-0.7). Patients treated with thyroidectomy had a better overall and cause specific survival, but the effect of CLND was not statistically significant after adjustment for other factors. CONCLUSIONS: In MTC, we did not find that race, gender or SES influenced the presentation, treatment or outcomes of patients with MTC. Men with MTC present with larger tumors and are less likely to have localized disease. Half of the MTC patients in California do not undergo a CLND at the time of thyroidectomy, which may suggest a lack appropriate care across a range of healthcare systems. PMID- 27563562 TI - Complications and oncologic outcomes of pedicled transverse rectus abdominis myocutaneous flap in breast cancer patients. AB - BACKGROUND: There are several techniques for harvesting the pedicled transverse rectus abdominis myocutaneous (TRAM) flap after mastectomy in breast cancer patients. We examined the whole muscle with partial sheath sparing technique and determined factors associated with its complications and oncological outcomes. METHODS: We retrospectively reviewed the results of 168 TRAM flaps performed between January 2003 and December 2010, focusing on complications and oncologic outcomes. RESULTS: Among the 168 pedicled TRAM flap procedures in 158 patients, flap complications occurred in 34%. Most of the flap complications included some degree of fat necrosis. There was no total flap loss. Flap complications were associated with elderly patients and the presence of major donor site complications. Abdominal bulging and hernia occurred in 12% of patients. The bi pedicled TRAM flap and higher body mass index (BMI) were significant factors associated with increased donor site complications. Seven patients (4%) developed loco-regional recurrence. Within a median follow-up of 27 months, distant metastasis and death occurred in 6% and 4% of patients, respectively. CONCLUSIONS: The pedicled TRAM flap using the whole muscle with partial sheath sparing technique in the present study is consistent with the results from previous studies in flap complication rates and oncological outcomes. PMID- 27563563 TI - Breast reconstruction at the MD Anderson Cancer Center. AB - The introduction of the transverse rectus abdominis myocutaneous flap in the 1970s marks the beginning of modern breast reconstruction although implants were available even earlier mainly for breast augmentation. Mastectomy techniques have evolved from the early Halsted radical mastectomy to the modern skin sparing mastectomy. The latter made possible using implants for breast reconstruction. Although prosthetic reconstruction provides a simpler procedure with quick recovery, autologous reconstruction offers more natural and long-lasting results especially in the setting of radiotherapy. Both forms have been extensively used at the MD Anderson Cancer Center (MDACC) while microsurgical breast reconstruction has been the hallmark of the MDACC experience. One of the most challenging areas of breast reconstruction is how to achieve good results without compromising adjuvant therapy when post-mastectomy radiotherapy is required. Managing upper extremity lymphedema following breast cancer treatment is another difficult issue which has gained great attention in recent years. This article highlights the important work in various aspects of breast reconstruction that has been done at the MDACC. PMID- 27563564 TI - Oncoplastic central quadrantectomies. AB - Tumors localized in the central quadrant (centrally located breast tumors) have always represented a challenge for the surgeon because of the critical aesthetical matters related to the nipple-areola complex (NAC). Many years of experience with breast cancer patients treated by using various oncoplastic techniques, has allowed us to develop the modified hemibatwing for the treatment of central breast tumors, where the NAC is involved. Modified hemibatwing-along with the removal of the NAC-is a useful oncoplastic technique and it represents an ideal option for the treatment of central tumors because it assures oncological safety, a reduced surgical timetable and greater aesthetical results. PMID- 27563565 TI - Hepatic artery reinforcement after post pancreatectomy haemorrhage caused by pancreatitis. AB - Post-pancreatectomy hemorrhage (PPH) is a major complication occurring in 6-8% of patients after pancreaticoduodenectomy (PD). Arterial bleeding is the most frequent cause. Mortality rate could reach 30% after grade C PPH according to ISGPS classification. Complete interruption of hepatic arterial flow has to be a salvage procedure because of the high risk of intrahepatic abscess following the procedure. We report a technique to perform an artery reinforcement after PPH caused by pancreatitis. A PD according to Whipple's procedure with child's reconstruction was performed in a 68-year-old man. At postoperative day 12, the patient presented a sudden violent abdominal pain with arterial hypotension and tachycardia. Computed tomography (CT) with intravenous contrast injection was performed. Arterial and venous phases showed a contrast extravasation on the hepatic artery. Origin of PPH was found as an erosion of hepatic artery caused by pancreatic leak. A peritoneal patch was placed around hepatic artery to reinforce damaged arterial wall. The peritoneal patch was harvested from right hypochondrium with a thin preperitoneal fat layer. The patch was sutured around hepatic artery with musculoaponeurotic face placed on the arterial wall. A CT was performed and hepatic artery was permeable with normal caliber in the portion of peritoneal patch reinforcement. The technique described in the present case consists in reinforcing directly arterial wall after occurrence of PPH. The use of a peritoneal patch during pancreatic surgery has first been described to replace a portion of portal vein after venous resection with the peritoneal layer placed on the intraluminal side of the vein. The present case describes a salvage technique to reinforce damaged artery after PPH in context of pancreatic leak. This simple technique could be useful to avoid complex arterial reconstruction and recurrent bleeding in septic context. PMID- 27563566 TI - Management dilemma of thyroid nodules in patients with malignant struma ovarii. AB - Struma ovarii is a rare type of ovarian teratoma comprised of at least 50% thyroid tissue. While most are benign, 70% of malignant cases are diagnosed as papillary carcinoma. Management of patients with thyroid nodules following gynecologic surgery remains controversial and variable. Historically, the treatment of choice has been surgical removal to rule out ovarian carcinoma. Thyroid follow-up and further treatment options are guided by tumor characteristics. The patient in this case presented to the endocrine surgeon with multiple thyroid nodules, dysphagia and a history of struma ovarii that was surgically treated at an outside hospital. Fine needle aspiration demonstrated benign histology. However, due to compressive symptoms and uncertainty of other nodules, the patient underwent a total thyroidectomy. Due to limited published data and treatment guidelines regarding thyroid nodules in patients with a history of malignant struma ovarii, surgery was recommended to rule out papillary thyroid carcinoma and relieve the patient's dysphagia. More research focused on treatment and outcomes of struma ovarii patients with thyroid nodules is essential to establish treatment guidelines for these patients. PMID- 27563567 TI - Bilateral giant juvenile fibroadenomas of the breasts-a rare indication for bilateral skin reducing mastectomy. AB - Fibroadenoma is the most common benign tumor of the breast but giant juvenile fibroadenoma represent only 0.5% of all fibroadenomas and when bilateral are much more rare. We describe the case of a 25 years old girl that presented with bilateral giant juvenile fibroadenomas and was treated by bilateral skin reducing mastectomy using the inferior dermal flap, implant, and free nipple graft. PMID- 27563568 TI - Interdisciplinary Researches in Iran V: Toward Interdisciplinary Technologies. PMID- 27563569 TI - Performance Improvement of the Goertzel Algorithm in Estimating of Protein Coding Regions Using Modified Anti-notch Filter and Linear Predictive Coding Model. AB - The aim of this paper is to improve the performance of the conventional Goertzel algorithm in determining the protein coding regions in deoxyribonucleic acid (DNA) sequences. First, the symbolic DNA sequences are converted into numerical signals using electron ion interaction potential method. Then by combining the modified anti-notch filter and linear predictive coding model, we proposed an efficient algorithm to achieve the performance improvement in the Goertzel algorithm for estimating genetic regions. Finally, a thresholding method is applied to precisely identify the exon and intron regions. The proposed algorithm is applied to several genes, including genes available in databases BG570 and HMR195 and the results are compared to other methods based on the nucleotide level evaluation criteria. Results demonstrate that our proposed method reduces the number of incorrect nucleotides which are estimated to be in the noncoding region. In addition, the area under the receiver operating characteristic curve has improved by the factor of 1.35 and 1.12 in HMR195 and BG570 datasets respectively, in comparison with the conventional Goertzel algorithm. PMID- 27563570 TI - Application of Hyperelastic-based Active Mesh Model in Cardiac Motion Recovery. AB - Considering the nonlinear hyperelastic or viscoelastic nature of soft tissues has an important effect on modeling results. In medical applications, accounting nonlinearity begets an ill posed problem, due to absence of external force. Myocardium can be considered as a hyperelastic material, and variational approaches are proposed to estimate stiffness matrix, which take into account the linear and nonlinear properties of myocardium. By displacement estimation of some points in the four-dimensional cardiac magnetic resonance imaging series, using a similarity criterion, the elementary deformations are estimated, then using the Moore-Penrose inverse matrix approach, all point deformations are obtained. Using this process, the cardiac wall motion is quantized to mechanically determine local parameters to investigate the cardiac wall functionality. This process was implemented and tested over 10 healthy and 20 patients with myocardial infarction. In all patients, the process was able to precisely determine the affected region. The proposed approach was also compared with linear one and the results demonstrated its superiority respect to the linear model. PMID- 27563571 TI - Extraction of the Best Frames in Coronary Angiograms for Diagnosis and Analysis. AB - X-ray coronary angiography has been a gold standard in the clinical diagnosis and interventional treatment of coronary arterial diseases for decades. In angiography, a sequence of images is obtained, a few of which are suitable for physician inspection. This paper proposes an automatic algorithm for the extraction of one or more frames from an angiogram sequence, which is most suitable for diagnosis and analysis by experts or processors. The algorithm consists of two stages: In the first stage, the background and illumination in the angiogram sequence are omitted. By analyzing the histogram of the sequence, a feature is attributed to each frame. These features, determining the visibility of the vessel tree, are clustered by a fuzzy c-means method. In the second stage, the cardiac phase for each frame is specified. Using the results of both stages, the best frames in an angiogram sequence are obtained. To evaluate the proposed method, it has been tested on angiogram sequences from several patients. The results demonstrate the accuracy of the method. The performance and speed of our method indicate its usefulness in clinical applications. PMID- 27563572 TI - Detecting Gait Phases from RGB-D Images Based on Hidden Markov Model. AB - Gait contains important information about the status of the human body and physiological signs. In many medical applications, it is important to monitor and accurately analyze the gait of the patient. Since walking shows the reproducibility signs in several phases, separating these phases can be used for the gait analysis. In this study, a method based on image processing for extracting phases of human gait from RGB-Depth images is presented. The sequence of depth images from the front view has been processed to extract the lower body depth profile and distance features. Feature vector extracted from image is the same as observation vector of hidden Markov model, and the phases of gait are considered as hidden states of the model. After training the model using the images which are randomly selected as training samples, the phase estimation of gait becomes possible using the model. The results confirm the rate of 60-40% of two major phases of the gait and also the mid-stance phase is recognized with 85% precision. PMID- 27563573 TI - Three-dimensional Segmentation of Retinal Cysts from Spectral-domain Optical Coherence Tomography Images by the Use of Three-dimensional Curvelet Based K-SVD. AB - This paper presents a new three-dimensional curvelet transform based dictionary learning for automatic segmentation of intraretinal cysts, most relevant prognostic biomarker in neovascular age-related macular degeneration, from 3D spectral-domain optical coherence tomography (SD-OCT) images. In particular, we focus on the Spectralis SD-OCT (Heidelberg Engineering, Heidelberg, Germany) system, and show the applicability of our algorithm in the segmentation of these features. For this purpose, we use recursive Gaussian filter and approximate the corrupted pixels from its surrounding, then in order to enhance the cystoid dark space regions and future noise suppression we introduce a new scheme in dictionary learning and take curvelet transform of filtered image then denoise and modify each noisy coefficients matrix in each scale with predefined initial 3D sparse dictionary. Dark pixels between retinal pigment epithelium and nerve fiber layer that were extracted with graph theory are considered as cystoid spaces. The average dice coefficient for the segmentation of cystoid regions in whole 3D volume and with-in central 3 mm diameter on the MICCAI 2015 OPTIMA Cyst Segmentation Challenge dataset were found to be 0.65 and 0.77, respectively. PMID- 27563574 TI - Breathomics for Gastric Cancer Classification Using Back-propagation Neural Network. AB - Breathomics is the metabolomics study of exhaled air. It is a powerful emerging metabolomics research field that mainly focuses on health-related volatile organic compounds (VOCs). Since the quantity of these compounds varies with health status, breathomics assures to deliver noninvasive diagnostic tools. Thus, the main aim of breathomics is to discover patterns of VOCs related to abnormal metabolic processes occurring in the human body. Classification systems, however, are not designed for cost-sensitive classification domains. Therefore, they do not work on the gastric carcinoma (GC) domain where the benefit of correct classification of early stages is more than that of later stages, and also the cost of wrong classification is different for all pairs of predicted and actual classes. The aim of this work is to demonstrate the basic principles for the breathomics to classify the GC, for that the determination of VOCs such as acetone, carbon disulfide, 2-propanol, ethyl alcohol, and ethyl acetate in exhaled air and stomach tissue emission for the detection of GC has been analyzed. The breath of 49 GC and 30 gastric ulcer patients were collected for the study to distinguish the normal, suspected, and positive cases using back propagation neural network (BPN) and produced the accuracy of 93%, sensitivity of 94.38%, and specificity of 89.93%. This study carries out the comparative study of the result obtained by the single- and multi-layer cascade-forward and feed forward BPN with different activation functions. From this study, the multilayer cascade-forward outperforms the classification of GC from normal and benign cases. PMID- 27563575 TI - Automatic Recognition of Acute Myelogenous Leukemia in Blood Microscopic Images Using K-means Clustering and Support Vector Machine. AB - Acute myelogenous leukemia (AML) is a subtype of acute leukemia, which is characterized by the accumulation of myeloid blasts in the bone marrow. Careful microscopic examination of stained blood smear or bone marrow aspirate is still the most significant diagnostic methodology for initial AML screening and considered as the first step toward diagnosis. It is time-consuming and due to the elusive nature of the signs and symptoms of AML; wrong diagnosis may occur by pathologists. Therefore, the need for automation of leukemia detection has arisen. In this paper, an automatic technique for identification and detection of AML and its prevalent subtypes, i.e., M2-M5 is presented. At first, microscopic images are acquired from blood smears of patients with AML and normal cases. After applying image preprocessing, color segmentation strategy is applied for segmenting white blood cells from other blood components and then discriminative features, i.e., irregularity, nucleus-cytoplasm ratio, Hausdorff dimension, shape, color, and texture features are extracted from the entire nucleus in the whole images containing multiple nuclei. Images are classified to cancerous and noncancerous images by binary support vector machine (SVM) classifier with 10 fold cross validation technique. Classifier performance is evaluated by three parameters, i.e., sensitivity, specificity, and accuracy. Cancerous images are also classified into their prevalent subtypes by multi-SVM classifier. The results show that the proposed algorithm has achieved an acceptable performance for diagnosis of AML and its common subtypes. Therefore, it can be used as an assistant diagnostic tool for pathologists. PMID- 27563576 TI - Student assessment: Moving over to programmatic assessment. PMID- 27563577 TI - Concept maps: A tool for knowledge management and synthesis in web-based conversational learning. AB - Web-based conversational learning provides an opportunity for shared knowledge base creation through collaboration and collective wisdom extraction. Usually, the amount of generated information in such forums is very huge, multidimensional (in alignment with the desirable preconditions for constructivist knowledge creation), and sometimes, the nature of expected new information may not be anticipated in advance. Thus, concept maps (crafted from constructed data) as "process summary" tools may be a solution to improve critical thinking and learning by making connections between the facts or knowledge shared by the participants during online discussion This exploratory paper begins with the description of this innovation tried on a web-based interacting platform (email list management software), FAIMER-Listserv, and generated qualitative evidence through peer-feedback. This process description is further supported by a theoretical construct which shows how social constructivism (inclusive of autonomy and complexity) affects the conversational learning. The paper rationalizes the use of concept map as mid-summary tool for extracting information and further sense making out of this apparent intricacy. PMID- 27563578 TI - Professionalism and ethics: A proposed curriculum for undergraduates. AB - Professionalism is the attributes, behaviors, commitments, values, and goals that characterize a profession. In medical professional, it encompasses strong societal role and involves emotional component too. On the other hand, ethics is the study of morality - careful and systematic analysis of moral decisions and behaviors and practicing those decisions. Medical ethics focuses primarily on issues arising out of the practice of medicine. It is generally believed that professionalism and ethics are caught by watching your teachers and seniors and not taught formally. Professionalism and ethics are previously diffused passively to the students through "the hidden curriculum," leaving a lot to chance. However, over the time, it has been advocated that graduates need to be formally trained in the concepts of professionalism and ethics. In this paper, we propose a formal curriculum on professionalism and ethics, tailor-made for Indian medical graduates. PMID- 27563579 TI - Role of computer-based learning in tooth carving in dentistry: An Indian perspective. AB - Tooth carving is an important practical preclinical exercise in the curriculum in Indian dental education setup. It forms the basis of introduction to tooth anatomy, morphology and occlusion of primary and permanent teeth through practical approach. It requires enormous time and manpower to master the skill. Therefore, there is an imminent necessity to incorporate computer-based learning of the art of tooth carving for effective teaching and efficient student learning. This will ensure quality time to be spent on other academic and research activities by students and faculty in addition to adding value as a teaching aid. PMID- 27563580 TI - Finding self-directed learning readiness and fostering self-directed learning through weekly assessment of self-directed learning topics during undergraduate clinical training in ophthalmology. AB - BACKGROUND: To know the individual's current level of readiness and to manage self-directed learning (SDL) not only help learners but also the instructors. The objectives of this study were to find SDL readiness among 4(th) year medical student and to analyze the effect of weekly assessment of SDL topics. METHODOLOGY: This was a cross-sectional study to analyze the effect of weekly assessment of SDL topics in fostering SDL. The 51 4(th) year students during a clinical posting in ophthalmology participated for this study. Each recruited student was tested for SDL readiness through the SDL readiness scale (SDLRS) developed by Lucy Guglielmino (1978), which was validated in our local setting and responses were collected from students on the 1(st) day of the clinical posting. The students chose SDL topics which were assessed on a weekly basis in the form of scenario-based multiple choice questionnaires. Written feedback was collected from each student regarding such activity during their clinical posting, especially to know the actual utilization of SDL hours provided in teaching schedule, satisfaction on the type of questions and motivation for SDL. RESULTS: The mean SDLRS score in male students were 214.15 +/- 19.73 and in female 207.95 +/- 17.983, which falls under average score as defined in Guglielmino scale. The majority of study population expressed better utilization of SDL study hours because of weekly assessment than when they had no assessment for SDL. CONCLUSIONS: Majority of the study population were found to be ready for SDL. The weekly assessment of SDL topics was found to stimulate proper utilization of SDL slots in teaching schedule thereby fostering SDL habits. PMID- 27563581 TI - Item analysis of in use multiple choice questions in pharmacology. AB - BACKGROUND: Multiple choice questions (MCQs) are a common method of assessment of medical students. The quality of MCQs is determined by three parameters such as difficulty index (DIF I), discrimination index (DI), and distracter efficiency (DE). OBJECTIVES: The objective of this study is to assess the quality of MCQs currently in use in pharmacology and discard the MCQs which are not found useful. MATERIALS AND METHODS: A class test of central nervous system unit was conducted in the Department of Pharmacology. This test comprised 50 MCQs/items and 150 distracters. A correct response to an item was awarded one mark with no negative marking for incorrect response. Each item was analyzed for three parameters such as DIF I, DI, and DE. RESULTS: DIF of 38 (76%) items was in the acceptable range (P = 30-70%), 11 (22%) items were too easy (P > 70%), and 1 (2%) item was too difficult (P < 30%). DI of 31 (62%) items was excellent (d > 0.35), of 12 (24%) items was good (d = 0.20-0.34), and of 7 (14%) items was poor (d < 0.20). A total of 50 items had 150 distracters. Among these, 27 (18%) were nonfunctional distracters (NFDs) and 123 (82%) were functional distracters. Items with one NFD were 11 and with two NFDs were 8. Based on these parameters, 6 items were discarded, 17 were revised, and 27 were kept for subsequent use. CONCLUSION: Item analysis is a valuable tool as it helps us to retain the valuable MCQs and discard the items which are not useful. It also helps in increasing our skills in test construction and identifies the specific areas of course content which need greater emphasis or clarity. PMID- 27563582 TI - Impact of patient-based teaching in improving prescription writing skills of II MBBS students. AB - BACKGROUND: Although prescription writing is a part of the medical students' curriculum, their prescribing skills are still poor either as a part of their examinations or as they go out as qualified health professionals which may be due to inadequate training. Educational intervention like patient-based teaching in pharmacology offers lifelike preparation and provides more relevance, easier recall, and help in improving prescribing skills. This study aims to determine the role of patient-based teaching in improving the prescribing skill of II year medical students compared to conventional case-based teaching. MATERIALS AND METHODS: This prospective, comparative study was carried out after giving orientation to prescription writing as per the WHO prescribing guidelines (N = 50). The 25 students in control group were given case-based teaching and 25 students in test group were given patient-based teaching of prescription writing for the same five common clinical conditions. The prescription writing skill (knows how level) was assessed by evaluating the prescriptions written in the prescribed format and scored by a 14-point scoring system. RESULTS: The mean scores obtained by the control (9.6) and test (12.04) groups were compared by unpaired Student's t-test (P < 0.001). On comparing the individual parameters in the 14-point scoring by Chi-square test, significant difference was found regarding patient and doctor's particulars, diagnosis, quantity, duration of therapy, and signature between study groups. Student feedback revealed that patient-based teaching enhanced responsibility, focus, and memory. CONCLUSION: Patient-based approach for prescription writing enables students to develop prescribing skills in a complete and professional way. PMID- 27563583 TI - Students' feedback: An effective tool in teachers' evaluation system. AB - BACKGROUND: Evaluation is an integral part of medical education. Although there are various methods of teachers' evaluation, student's feedback is considered as the most effective and reliable method albeit a controversial one. In this study, we have tried to evaluate the effectiveness of the students' feedback in teachers' evaluation in an upcoming medical college. AIM: The aim of this study was to improve the quality of teaching by introducing students' feedback as a teachers' evaluation system in a new medical college. MATERIALS AND METHODS: A feedback of second professional teachers was obtained from the fourth-semester students. This feedback was obtained through a proforma which was validated through peer review. Based on the feedback, teachers were informed about their strengths and weaknesses in a confidential manner. A uniform opportunity was then provided to these teachers for 3 months to improve their teaching skills. At the end of the period, again a questionnaire was administered to both the students and the teachers to assess the effectiveness of the feedback system. RESULTS: More than two-third of the students and teachers alike agreed that the student's feedback is an effective tool for the faculty development. Majority of the teachers were satisfied with the present format of the feedback system and agreed that it sensitized them toward the students need. CONCLUSIONS: Student's feedback is an effective tool for teachers' evaluation resulting in faculty development. However, other sources of feedback may also be utilized for the overall assessment of a teacher. PMID- 27563584 TI - Vertical integration of basic science in final year of medical education. AB - BACKGROUND: Development of health professionals with ability to integrate, synthesize, and apply knowledge gained through medical college is greatly hampered by the system of delivery that is compartmentalized and piecemeal. There is a need to integrate basic sciences with clinical teaching to enable application in clinical care. AIM: To study the benefit and acceptance of vertical integration of basic science in final year MBBS undergraduate curriculum. MATERIALS AND METHODS: After Institutional Ethics Clearance, neuroanatomy refresher classes with clinical application to neurological diseases were held as part of the final year posting in two medical units. Feedback was collected. Pre- and post-tests which tested application and synthesis were conducted. Summative assessment was compared with the control group of students who had standard teaching in other two medical units. In-depth interview was conducted on 2 willing participants and 2 teachers who did neurology bedside teaching. RESULTS: Majority (>80%) found the classes useful and interesting. There was statistically significant improvement in the post-test scores. There was a statistically significant difference between the intervention and control groups' scores during summative assessment (76.2 vs. 61.8 P < 0.01). Students felt that it reinforced, motivated self-directed learning, enabled correlations, improved understanding, put things in perspective, gave confidence, aided application, and enabled them to follow discussions during clinical teaching. CONCLUSION: Vertical integration of basic science in final year was beneficial and resulted in knowledge gain and improved summative scores. The classes were found to be useful, interesting and thought to help in clinical care and application by majority of students. PMID- 27563585 TI - Introduction of active learning method in learning physiology by MBBS students. AB - CONTEXT: Active learning has received considerable attention over the past several years, often presented or perceived as a radical change from traditional instruction methods. Current research on learning indicates that using a variety of teaching strategies in the classroom increases student participation and learning. AIM AND OBJECTIVES: To introduce active learning methodology, i.e., "jigsaw technique" in undergraduate medical education and assess the student and faculty response to it. SUBJECTS AND METHODS: This study was carried out in the Department of Physiology in a Medical College of North India. A topic was chosen and taught using one of the active learning methods (ALMs), i.e., jigsaw technique. An instrument (questionnaire) was developed in English through an extensive review of literature and was properly validated. The students were asked to give their response on a five-point Likert scale. The feedback was kept anonymous. Faculty also provided their feedback in a separately provided feedback proforma. The data were collected, compiled, and analyzed. RESULTS: Of 150 students of MBBS-first year batch 2014, 142 participated in this study along with 14 faculty members of the Physiology Department. The majority of the students (>90%) did welcome the introduction of ALM and strongly recommended the use of such methods in teaching many more topics in future. 100% faculty members were of the opinion that many more topics shall be taken up using ALMs. CONCLUSION: This study establishes the fact that both the medical students and faculty want a change from the traditional way of passive, teacher-centric learning, to the more active teaching-learning techniques. PMID- 27563586 TI - Experience of Delphi technique in the process of establishing consensus on core competencies. AB - INTRODUCTION: The Department of Community Medicine and Family Medicine (CMFM) has been started as a new model for imparting the components of family medicine and delivering health-care services at primary and secondary levels in all six newly established All India Institute of Medical Sciences (AIIMS), but there is no competency-based curriculum for it. The paper aims to share the experience of Delphi method in the process of developing consensus on core competencies of the new model of CMFM in AIIMS for undergraduate medical students in India. METHODS: The study adopted different approaches and methods, but Delphi was the most critical method used in this research. In Delphi, the experts were contacted by e mail and their feedback on the same was analyzed. RESULTS: Two rounds of Delphi were conducted in which 150 participants were contacted in Delphi-I but only 46 responded. In Delphi-II, 26 participants responded whose responses were finally considered for analysis. Three of the core competencies namely clinician, primary care physician, and professionalism were agreed by all the participants, and the least agreement was observed in the competencies of epidemiologist and medical teacher. The experts having more experience were less consistent as responses were changed from agree to disagree in more than 15% of participants and 6% changed from disagree to agree. CONCLUSION: Within the given constraints, the final list of competencies and skills for the discipline of CMFM compiled after the Delphi process will provide a useful insight into the development of competency-based curriculum of the subject. PMID- 27563587 TI - Effectiveness of modified seminars as a teaching-learning method in pharmacology. AB - CONTEXT: Student-led seminars (SLS) are adopted as a teaching-learning (T-L) method in pharmacology. Previous studies assessing the feedback on T-L methods in pharmacology points out that the traditional seminars consistently received poor feedbacks as they were not favorite among the students. AIMS: This study aimed to obtain feedback on traditional SLS, introduce modified SLS and compare the modified seminars with the traditional ones. SETTINGS AND DESIGN: This was a prospective interventional study done for 2 months in medical undergraduates of fifth semester attending Pharmacology seminars at a Government Medical College in South India. SUBJECTS AND METHODS: Structured questionnaire was used to elicit feedback from participants. The responses were coded on 5-point Likert scale. Modifications in seminar sessions such as role plays, quiz, tests, group discussion, and patient-oriented problem-solving exercises were introduced along with SLS. STATISTICAL ANALYSIS USED: The data were analyzed using SPSS version 16. The descriptive data were expressed using frequencies and percentages. Wilcoxon signed rank test, and Friedman tests were used to compare traditional with modified seminars. RESULTS: The participants identified interaction as the most important component of a seminar. Majority opined that the teacher should summarize at the end of SLS. Student feedback shows that modified seminars created more interest, enthusiasm, and inspiration to learn the topic when compared to traditional SLS. They also increased peer coordination and group dynamics. Students opined that communication skills and teacher-student interactions were not improved with modified seminars. CONCLUSIONS: Interventions in the form of modified SLS may be adopted to break the monotony of traditional seminars through active participation, peer interaction, and teamwork. PMID- 27563588 TI - Developing competency in interns for endotracheal intubation: An educational article. AB - BACKGROUND: Our existing undergraduate curriculum lacks developing competency for endotracheal intubation. Even though it is a lifesaving procedure, interns are exposed only during their posting in anesthesia or emergency medicine and so, when need arises, they fail to perform endotracheal intubation and it leads to catastrophes. AIMS AND OBJECTIVES: The aim of this study was to develop competency in interns for endotracheal intubation. MATERIALS AND METHODS: A study was conducted on fifty interns of medical college. Lecture and demonstration were used for cognitive domain and one-to-one training and practice on manikin for affective and psychomotor domains, respectively. Live demonstration on patients was done whenever possible. Gain in knowledge was evaluated by pre- and post-test using standardized validated questionnaire. Skills were assessed by direct observation of procedural skill on manikin, split in steps: Laryngoscopy, intubation, and ventilation. Session was evaluated using feedback questionnaire and Likert scale. RESULTS: Interns showed mean marks of 8.12 +/- 1.63 in pretest compared to 13.86 +/- 1.06 of posttest with a gain of 34.8% (P = 0.0001), which is highly significant. Twenty-two percent interns completed all steps correctly in the first attempt, 62% in the second attempt, while 16% required third attempt to correctly complete all steps. CONCLUSION: This training developed competency for basic knowledge and practice of endotracheal intubation in interns adequately on manikin. Training for endotracheal intubation should be carried out at the beginning of internship before they go for clinical practice and repeated during their rotation of Anesthesia and Emergency Medicine Department, so they can retain their competency for it and can do later on whenever required. PMID- 27563589 TI - Evaluation of impact of teaching clinical pharmacology and rational therapeutics to medical undergraduates and interns. AB - OBJECTIVES: To find out the impact of teaching clinical pharmacology and rational therapeutics (CPT) to medical undergraduates (UGs) and interns. MATERIALS AND METHODS: This cross-sectional, prospective study was conducted on three UGs batches and interns using two pretested validated structured questionnaires, modified from the work of Tobaiqy et al. The study was approved by the Institutional Ethics Committee. ANOVA and Chi-square test were used for statistical analysis. The value of P < 0.05 was considered statistically significant. RESULTS: A total of 379 UGs and 96 interns participated in this study. Mean knowledge score of interns was significantly reduced as compared to UGs (P < 0.0001). A significant increase in confidence for unsupervised prescribing of nonsteroidal anti-inflammatory drugs (99%), oral rehydration salt, iron salts was perceived among interns as compared to UGs (P < 0.05). However, 63.5% confessed problems in selection of drugs, drug-drug interactions, prescribing in special patient population. Although they were confident prescribing fixed dose combination for adult patients (89.5%), majority were hesitant to prescribe opioids (77%), steroids (76%), vaccines (75%), and antihypertensives (62%). CONCLUSION: The theoretical CPT teaching transfers knowledge to UGs; however, it is not retained in internship and does not adequately prepare interns to prescribe safe and rational drugs. PMID- 27563590 TI - Is "modular" the way to go for small group learning in community medicine in undergraduate clinical postings? AB - CONTEXT: There is a need to shift from the didactic lecture-based instruction to more student-centered active learning methods for undergraduate teaching in community medicine. AIMS: To compare didactic and modular method of learning on Level 1 and 2 on Kirkpatrick's training evaluation model. SETTINGS AND DESIGN: This was a two-arm educational intervention study for a small group of the 2(nd) year MBBS students in their 4(th) semester during clinical posting in the subject of community medicine. SUBJECTS AND METHODS: The topic chosen was "rabies prophylaxis" in the 2(nd) clinical posting during 4(th) semester. With permission from Institutional Ethics Committee, first batch of 17 students was taught this topic by didactic method. Next batch of 22 students was taught by the modular method. A self-reading module was prepared for this study and validated by three teachers. What was different in modular teaching was a circular sitting arrangement, module reading by students, video presentation, and exercise using case vignettes. STATISTICAL ANALYSIS USED: Student's t-test was used for pre- and post-test score comparison and Mann-Whitney U-test for students' responses on Likert scale. RESULTS: The mean gain in obtained marks after modular learning (7.9/15) was significantly higher as compared to gain after didactic teaching (5.9/15) (P = 0.0038); more students asserted to be confident to manage a case in modular group compared to the didactic group (P < 0.05) indicating a higher level of learning through modular teaching. CONCLUSIONS: Modular teaching fares better than didactic method and hence should be used more frequently in community medicine clinical posting. PMID- 27563591 TI - Effectiveness of integrated teaching module in pharmacology among medical undergraduates. AB - CONTEXT: Over the years with advancement of science and technology, each subject has become highly specialized. Teaching of medical students has still remained separate in various departments with no scope of integration in majority of medical institutes in India. Study was planned to have an experience of integration in institute and sensitize faculty for integrated teaching-learning (TL) method. AIMS: To prepare and test effectiveness of integrated teaching module for 2(nd) year MBBS student in pharmacology and to sensitize and motivate faculties toward advantages of implementing integrated module. SETTINGS AND DESIGN: Education intervention project implemented 2(nd) year MBBS students of Government Medical College and New Civil Hospital, Surat. SUBJECTS AND METHODS: Students of second MBBS were divided into two groups. One group was exposed to integrated teaching sessions and another to traditional method. Both the groups were assessed by pre- and post-test questionnaire, feedback and focus group discussions were conducted to know their experience about process. RESULTS: A total of 165 students of the 2(nd) year MBBS were exposed to the integrated teaching module for two topics in two groups. One group was taught by traditional teaching, and another group was exposed to the integrated TL session. Both the groups have shown a significant improvement in posttest scores but increase in mean score was more in integrated group. During analysis of feedback forms, it was noted that students preferred integrated TL methods since they help in better understanding. Faculty feedback shows consensus over the adaptation of integrated TL methods. CONCLUSIONS: Integrated TL sessions were well-appreciated by students and faculties. To improve the critical reasoning skills and self-directed learning of students, integrated TL is highly recommended for must know areas of curriculum. PMID- 27563592 TI - Impact of structured verbal feedback module in medical education: A questionnaire and test score-based analysis. AB - INTRODUCTION: Feedback is a divalent bond between the supplier (teacher) and the recipient (student). The strength of the bond depends on the instructional design of the feedback. Feedback is central to medical education in promoting self directed learning in students. In the present study, a structured verbal feedback module was prepared, implemented, and evaluated. METHODS: The study was done on 280 students from four consecutive batches (2011 to 2014) of the 1(st) year MBBS students exposed to different types and modes of feedback. Analysis was done using student feedback questionnaire for the perception of students to verbal feedback. Quantitative analysis using post hoc test and ANOVA for the impact of type of feedback (verbal or written) and effect of modes (individual or group) of verbal feedback on test score performance were done. RESULT: In this study, >=95% of the students preferred verbal feedback of both positive and negative attributes in student questionnaires. It was observed that verbal feedback sessions made a difference of up to 2-2.4 grade points in the mean score of batch when compared to the written feedback. The initial mean test score (T1) of 2011 + 2012 and 2013 + 2014 was not statistically significant (P = 0.113). But, in all subsequent tests (T2, T3, and T4), there was a statistically significant difference in the mean test scores (P = 0.000). CONCLUSION: (1) Students prefer verbal one-to-one feedback over written feedback. (2) Verbal feedback changes learning process and causes sustained improvement in learning strategies. PMID- 27563593 TI - Impact of self-assessment by students on their learning. AB - CONTEXT: Tutor assessment is sometimes also considered as an exercise of power by the assessor over assesses. Student self-assessment is the process by which the students gather information about and reflect on their own learning and is considered to be a very important component of learning. AIM: The primary objective of this study was to analyze the impact of self-assessment by undergraduate medical students on their subsequent academic performance. The secondary objective was to obtain the perception of students and faculty about self-assessment as a tool for enhanced learning. MATERIALS AND METHODS: The study was based on the evaluation of two theory tests consisting of both essay type and short answer questions, administered to students of the 1(st) year MBBS (n = 89). They self-assessed their performance after 3 days of the first test followed by marking of faculty and feedback. Then, a nonidentical theory test on the same topic with the same difficulty level was conducted after 7 days and assessed by the teachers. The feedback about the perception of students and faculty about this intervention was obtained. RESULTS: Significant improvement in the academic performance after the process of self-assessment was observed (P < 0.001). There was a significantly positive correlation between student and teacher marking (r = 0.79). Both students and faculty perceived it to be helpful for developing self directed learning skills. CONCLUSIONS: Self-assessment can increase the interest and motivation level of students for the subjects leading to enhanced learning and better academic performance, helping them in development of critical skills for analysis of their own work. PMID- 27563594 TI - Autopsy as a tool for learning gross anatomy during 1(st) year MBBS. AB - INTRODUCTION: Embalmed cadavers are the primary tool for teaching anatomy. However, difficulties are encountered due to changed color/texture of organs, hardening of tissues, and smell of formaldehyde. To overcome these difficulties, dissections on a fresh human body were shown to the 1(st) year MBBS students, and their perception was noted. MATERIALS AND METHODS: After taking universal precautionary measures, postmortem dissections were shown to students on voluntary donated bodies in the dissection hall, in addition to the traditional teaching on embalmed cadavers. Feedback was taken from students and faculty regarding the utility of these sessions. RESULTS: Better appreciation of texture, orientation, location, and relations of organs in fresh body, integration of teaching, awareness of the process and laws related to body donations were the outcomes of the study. However, the smell and sight of blood was felt to be nauseating by some students, and some students were worried about the spread of infectious diseases. CONCLUSIONS: Visualizing single fresh body dissection during 1(st) year professional MBBS is recommended either on medicolegal autopsy or on voluntarily-donated bodies. PMID- 27563595 TI - Erratum: Effectiveness of discharge planning on physical quality of life of patients with ischemic heart disease. AB - [This corrects the article on p. 129 in vol. 6, PMID: 27127744.]. PMID- 27563596 TI - In situ vasculogenesis: The potential role of mesenchymal stem cells in craniofacial reconstruction. PMID- 27563597 TI - Unfavorable outcome of unilateral cleft lip repair. PMID- 27563598 TI - The use of superficial cervical plexus block in oral and maxillofacial surgical practice as an alternative to general anesthesia in selective cases. AB - AIM: (1) To assess the feasibility, safety, and effectiveness of superficial cervical plexus (SCP) block in oral and maxillofacial surgical (OMFS) practice as an alternative to general anesthesia in selective cases. (2) To assess any associated complication specifically related to the procedure. SUBJECTS AND METHODS: The total number of patients was 10, out of which 6 were male and 4 were female patients. Six patients had incision and drainage of perimandibular space infections, two patients had Level Ib cervical lymph node biopsies, one patient had enucleation of cyst in the body of mandible, one patient had open reduction and internal fixation isolated angle fracture. Informed written consent was obtained from the patients after they had the procedure explained to them. Exclusion criteria included patient's refusal to undergo the procedure under regional anesthesia, allergy to local anesthetic, excessively anxious, and apprehensive patients, significant upper airway compromise warranting an endotracheal intubation to secure airway. All patients had the procedure done by the same operating surgeon. All patients had their surgical procedures under regional anesthesia (SCP block with supplemental nerve blocks) performed by the same surgeon with satisfactory anesthesia and analgesia without any complication. RESULTS: SCP block with concomitant mandibular nerve and long buccal nerve block has a high success rate, low complication rate, and high patient acceptability as shown in the study. CONCLUSION: The notable anesthetic effect and adequate working time, summed with the low risk of accidents and complications, make this technique a good alternative for sensitive blockage of part of the cranial and cervical regions and have positive outcomes in selective OMFS cases. PMID- 27563599 TI - Radiographic and histological evaluation of ectopic application of deproteinized bovine bone matrix. AB - OBJECTIVE: To evaluate, through radiographic and histological analysis, the tissue reaction induced by a biomaterial based on deproteinized bovine bone matrix (DBBM) in the muscle of sheep. MATERIALS AND METHODS: Sixteen sheep were used. The animals underwent surgery to insert polyethylene tubes containing the biomaterial in the muscle of the lower back (ectopic site) and were euthanized after 3 and 6 months. Each sheep received three tubes: Group 1 - sham group (negative control - tube without biomaterial), Group 2 - particulate autogenous bone (positive control), and Group 3 - DBBM biomaterial (GenOx Inorg). The material removed was evaluated by radiographic, macroscopic, and microscopic analysis, descriptively. RESULTS: Macroscopic analysis showed that Group 3 had a greater tissue volume maintenance. Microscopic analysis indicated that Group 1 had a higher concentration of dense, thin collagen fibers (3 and 6 months); in Group 2, there was a decrease in the inflammatory process and the deposition of dense, thin collagen fibers (3 and 6 months); in Group 3, the presence of a dense connective tissue was noted, in which the DBBM particles (3 months) were found. On the periphery of these particles, a deposition of basophilic material was found, indicating the formation of mineral particles and the formation of tissues with osteoid characteristics (6 months). CONCLUSION: Based on the results obtained, it can be concluded that the biomaterial based on DBBM led to the formation of tissue with similar characteristics to an osteoid matrix in a postoperative period of 6 months. However, none of the groups evaluated showed ectopic bone neoformation. PMID- 27563600 TI - Large ameloblastic fibro-odontoma in a 7-year-old girl with analysis of 108 cases. AB - BACKGROUND: Odontogenic tumors such as ameloblastic fibro-odontoma (AFO) are rare conditions in children and are often asymptomatic. AFOs are found by routine clinical and radiological examination or when they cause obvious intra- or extra oral swelling. MATERIALS AND METHODS: A case of an AFO in a 7-year-old girl is described, and 107 cases from the literature and this report are analyzed. RESULTS: The total of 108 cases revealed the average age at presentation of AFO to be 6.3 years in boys and 9.6 years in girls. There was a slight male predilection and AFO lesions most often occurred in the posterior mandible. AFO was almost always associated with an unerupted tooth or teeth. CONCLUSIONS: While the recurrence rate of AFO was found to be 5.5%, long-term postoperative clinical and radiological follow-up is advised to ensure no future signs of aggressive recurrence. PMID- 27563601 TI - Primary rhinocheiloplasty: Comparison of open and closed methods of alar cartilage reposition. AB - AIMS: To establish which rhinoplasty method for primary repairing of unilateral cleft lip (UCL) is better. SETTINGS AND DESIGN: Two patient groups with cleft lip were compared. Each group was operated on either by McComb's technique as closed rhinoplasty method or by Vissarionov-Kosin technique as an open method. SUBJECTS AND METHODS: First group included 29 patients and the second consisted of 31. All patients were operated on by single surgeon over 10 years. Randomization was based on wishes and intention of surgeon to use one of two methods. Evaluation of results was based on impartial data, and subjective information collected from respondents with different levels of knowledge about UCL. The objective scale was based on the evaluation of five noticeable residual deformations of nose that usually appear after primary lip-nose surgery: Alar flattening, low position of alar, widening or narrowing of nostril, and deformation of the upper part of nostril rim. Subjective evaluation was based on the opinion of respondents who were ranged every case depending on own judgment. STATISTICAL ANALYSIS: Was performed using Fisher method and Chi-square by Statistica 10.0, StatSoft Inc. RESULTS: Approach with general analysis indicated no difference between two methods. Despite of absence of clear differences between two groups we consider the closed rhinoplasty more favorable due to less damage to alar cartilages and no scars inside nostrils. CONCLUSIONS: We think that mentioned scarring may complicate secondary rhinoplasty, which is often needed to correct nose deformation. PMID- 27563602 TI - Intermaxillary fixation screws versus Erich arch bars in mandibular fractures: A comparative study and review of literature. AB - OBJECTIVE: Various techniques have been employed from time to time to achieve maxillomamdibular fixation. Although arch bars provide an effective and versatile means of maxillomandibular fixation, their use is not without shortcomings. However the introduction of intermaxillary fixation screws (IMF) has eliminated many of these issues of arch bars. The aim of the present study was to compare the advantages and disadvantages of intermaxillary fixation screws over the Erich arch bars in mandibular fractures. MATERIALS AND METHODS: Sixty dentulous patients who reported to Department of Oral and Maxillofacial Surgery, Al-Ameen Dental College and Hospital, Bijapur with mandibular fractures and required intermaxillary fixation as a part of treatment plan followd by open reduction and internal fixation under GA were selected and randomly divided into 2 groups of 30 patients each that is Group A and Group B. Group A included patients who received intermaxillary fixation with Erich arch bars. Group B includes patients who received intermaxillary fixation with IMF Screws. The parameters compared in both the groups included, surgical time taken, gloves perforation, post-operative occlusion, IMF stability, oral hygiene, patient acceptance and comfort and non vitality characteristics. RESULTS: The average surgical time taken and gloves perforations were more in Group A,the patient acceptance and oral hygiene was better in Group B, there was not much statistically significant difference in postoperative occlusion and IMF stability in both groups. Accidental root perforation was the only limitation of IMF screws. CONCLUSION: Intermaxillary fixation with IMF screws is more efficacious compared to Erich arch bars in the treatment of mandibular fractures. PMID- 27563603 TI - Pierre Robin sequence: Subdivision, data, theories, and treatment - Part 1: History, subdivisions, and data. AB - CONTEXT: The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists not only about the appropriate terminology and etiopathogenesis of the disorder but also about its management. Therefore, clinical findings and treatment outcomes of a large database of 266 PRS cases were compared with the current state of knowledge in scientific literature related to history, clinical description, diagnostic criteria, epidemiology, theories of oligohydramnios, mandibular catch-up growth, midfacial hyperplasia, and the timing of management. AIMS OF PART 1: Display disparities of the widely published subject of PRS that exist within the literature. SUBJECTS AND METHODS: A literature search related to diagnostic criteria was compared to findings of one of the largest PRS databases worldwide. RESULTS: Regarding diagnostic criteria two subdivisions, the Fairbairn-Robin triad (FRT) and the Siebold-Robin sequence (SRS) can be clearly distinguished. Both present with micrognathia and glossoptosis, the former with, the latter, however, without a palatal cleft. CONCLUSIONS: According to clear diagnostic criteria, PRS has to be subdivided in the future into FRT and SRS cases, as they may require different treatment approaches. PMID- 27563604 TI - Pierre Robin sequence: Subdivision, data, theories, and treatment - Part 2: Syndromic and nonsyndromic Pierre Robin sequence. AB - CONTEXT: The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists not only about the appropriate terminology and etiopathogenesis of the disorder but also about its management. Clinical findings and treatment outcomes of a large database of 266 PRS cases were compared with the current state of knowledge in the scientific literature, relating to history, clinical description, diagnostic criteria, epidemiology, theories of oligohydramnios, mandibular catch-up growth, midfacial hyperplasia, and the early management. AIMS OF PART 2: Contribute to the sparse scientific knowledge about pathogenesis and involved genetics. SUBJECTS AND METHODS: An analysis of this large database was conducted focusing on genetic involvement, family history, and the incidence of additional syndromes. RESULTS: Beside of differences related to clinical signs of dyspnea, feeding problems and mortality rates, various concomitant syndromes, and genetic abnormalities were found in cases of Fairbairn-Robin triad (FRT) and Siebold-Robin sequence (SRS), in addition to differences in relation to clinical signs of dyspnea, feeding problems, and mortality rates. CONCLUSION: Multiple FRT cases presented with various concomitant syndromes and genetic abnormalities, but only one type occurred in two SRS cases. The latter presented a significantly different mortality rate when compared to the FRT subgroup. PMID- 27563605 TI - Pierre Robin sequence: Subdivision, data, theories, and treatment - Part 3: Prevailing controversial theories related to Pierre Robin sequence. AB - CONTEXT: The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists not only about the appropriate terminology and etiopathogenesis of the disorder but also about its management. Therefore, clinical findings and treatment outcomes of a large database of 266 PRS cases were compared with the current state of knowledge in the scientific literature related to history, clinical description, diagnostic criteria, epidemiology, theories of oligohydramnios, mandibular catch-up growth, midfacial hyperplasia, and the early management. AIM: The aims of Part 3 debate the controversial biological theories relating to PRS. MATERIALS AND METHODS: Oligo /poly-hydramnios, mandibular catch-up growth, and midfacial hyperplasia, the three in the literature most prevailing theories related to PRS, have been compared and discussed with the findings provided by this large database of 266 Siebold-Robin sequence (SRS) and Fairbairn-Robin triad (FRT) cases. RESULTS: History and clinical findings evaluated in this database refute the first two theories. Although manifold midfacial appearances were demonstrated in FRT cases, a third of all SRS cases presented with mid-facial hyperplasia. CONCLUSION: The three main biological theories regarding PRS could not be verified after thorough analysis of the database. PMID- 27563607 TI - Lateral canthal repositioning in syndromic, antimongoloid slant. AB - INTRODUCTION: To report a single center's experience in correcting antimongoloid slant in Asian eyes using a minimally invasive approach. METHODS: Retrospective analysis of patients undergoing correction for antimongoloid slant at author's center, from 2007 to 2013 formed the study group. Concomitant surgical procedures were recorded. Pre- and post-operative photographs at the longest follow-up visit were analyzed and graded for functional and cosmetic outcomes. RESULTS: A total of 38 patients (76 eyelids) underwent successful correction to correct eyelid malposition. All patients' eyelids underwent exclusive lateral canthoplasty through a small incision in the upper eyelid crease and re-suspension technique, and 6 of them underwent bilateral slant correction simultaneously with additional cosmetic or corrective surgeries including hemifacial microsomia and Crouzon's syndrome. Of the 38 patients, 25 were females and 13 were males. The age of the population ranged from 7 to 48 years with a mean age of 27 years. Few instances of transient postoperative chemosis lasting up to 2 weeks and minor infections were reported. All cases showed improvement in eyelid position (as assessed clinically and on photographs), 2 pediatric cases required reoperation in the following 2 years for the recurrent lower eyelid malposition and/or lateral canthal deformity owing to deviated basal bone growth. DISCUSSION: Lateral canthoplasty with resuspension technique can effectively address antimongoloid slant for an esthetically desirable lateral canthus. PMID- 27563606 TI - Pierre Robin sequence: Subdivision, data, theories, and treatment - Part 4: Recommended management and treatment of Pierre Robin sequence and its application. AB - CONTEXT: The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists not only about the appropriate terminology and etiopathogenesis of the disorder but also about its management. Therefore, clinical findings and treatment outcomes of a large database of 266 PRS cases were compared with the current state of knowledge in the scientific literature related to history, clinical description, diagnostic criteria, epidemiology, theories of oligohydramnios, mandibular catch-up growth, midfacial hyperplasia, and early management. AIMS OF PART 4: To provide a systematic treatment protocol for Fairbairn-Robin triad (FRT) and Siebold Robin sequence (SRS) patients based on clinical findings and experience with 266 PRS cases. SUBJECTS AND METHODS: A plethora of treatment modalities and their outcome in literature have been compared to those applied in this database and their outcomes. RESULTS: The management of SRS/FRT depends on various factors including compromised airways, feeding difficulties, as well as the sequence of the reconstructive ladder. CONCLUSION: Based on the novel PRS subdivisions, a stepwise sequential treatment approach is outlined, addressing the particular needs of each disorder systematically. PMID- 27563608 TI - Retrospective evaluation of airway management with blind awake intubation in temporomandibular joint ankylosis patients: A review of 48 cases. AB - AIM: The aim was to determine the morbidity or mortality associated with the blind awake intubation technique in temporomandibular ankylosis patients. SETTINGS AND DESIGN: A total of 48 cases with radiographically and clinically confirmed cases of temporomandibular joint (TMJ) ankylosis were included in the study for evaluation of anesthetic management and its complications. MATERIALS AND METHODS: Airway assessment was done with standard proforma including Look externally, evaluate 3-3-2 rule, Mallampati classification, Obstruction, Neck mobility (LEMON) score assessment in all TMJ ankylosis patients. The intubation was carried out with the standard departmental anesthetic protocol in all the patients. The preoperative difficulty assessment and postoperative outcome were recorded. RESULTS: Blind awake intubation was done in 92% of cases, 6% of cases were intubated by fiberoptic awake intubation, and 2% patient required surgical airway. Ninety-eight percent of the patients were cooperative during the awake intubation. The frequent complications encountered during the blind awake intubation were epistaxis and sore throat. CONCLUSION: In an anesthetic setup, where fiberoptic intubation is not available, blind awake intubation could be considered in the anesthetic management algorithm. PMID- 27563609 TI - Warfare-related secondary anterior cranioplasty. AB - BACKGROUND: Anterior cranial bone defects secondary to global war cranial defects pose a unique reconstructive challenge. The objective of this study was to evaluate the outcomes of alloplastic reconstructions of cranial bone with titanium mesh and fat graft after warfare-related cranial trauma. PATIENTS AND METHODS: Thirty-five patients at the plastic and reconstructive surgery ward of our hospital underwent anterior cranioplasty with titanium mesh with or without fat grafts from lower abdominal wall. Inclusion criteria were anterior cranial bone defect due to warfare injuries, the mean age of these patients was 31 years (range, 23-48 years). Ninety-five percent were male, and 5% were female. Average follow-up was 12 months. Fat grafts were used to help obliterate endocranial dead spaces. RESULTS: Twenty-five patients (71%) had more than 0.5 cm dead space under cranial defects, and we used fat graft under the titanium mesh. The majority groups of patients (80%) were injured as a result of previous explosive device blasts with or without neurosurgical procedures in the past. The average patient age was 31 years, and 95% of patients were male. The mean anterior cranial defect size was 6 cm * 8 cm, and there were no wound infection or flap necrosis after operations. CONCLUSION: We recommend this procedure (titanium mesh with or without fat graft) for warfare injured cranial defects in secondary anterior cranial reconstructions. Fat grafts eliminates dead space and reduce secondary complications. PMID- 27563610 TI - Cleft Rhinoplasty- Columellar lengthening prolabial reconstruction with Abbe flap. AB - INTRODUCTION: A single center's experience of correction of cleft lip/palate associated rhinoplasty using Abbe flap is relatively rare in literature. The outcome and perception of the Abbe flap for cleft rhinoplasty at patient, surgeons, and patient's caregiver level have not been found in literature. This manuscript aims to address this lacuna through the use of rhinoplasty outcomes evaluation questionnaire (ROEQ). MATERIALS AND METHODS: A retrospective analysis of preoperative satisfaction and prospective analysis of postoperative satisfaction of patients who underwent cleft rhinoplasty were carried out using ROEQ. This was used twice measuring the pre- and post-operative periods. RESULTS: Twenty-one cases of bilateral cleft lip and palate who had earlier undergone (0.5 3 years back) cleft rhinoplasty and lip revision with Abbe's flap formed the study group. The mean age of the 21 subjects was 22.87 +/- 4.23 years. There were 13 males and 8 females forming the study group. The mean presurgical ROEQ score was 19.8 +/- 11.2, while the postsurgical score was 78.5 +/- 21.2. This difference was statistically significant (P = 0.001). The difference in score between the time period was 58.7%. DISCUSSION: From the ROEQ and other qualitative parameters, it is possible to demonstrate the impact of Abbe flap for cleft rhinoplasty and its impact on the quality of life of patients. Most of the patients and caregivers believed that this approach achieved a good or excellent postoperative result. The biological and operators factors behind such a success are discussed in light of previously published literature. PMID- 27563611 TI - Distraction osteogenesis in the treatment of temporomandibular joint ankylosis with mandibular micrognathia. AB - AIMS: The aims of the study were to evaluate the efficacy of simultaneous interpositional arthroplasty with distraction osteogenesis (DO) as a single procedure and to give the patient acceptable functional rehabilitation with correction of the gross facial asymmetry. MATERIALS AND METHODS: Nine patients of temporomandibular joint (TMJ) ankylosis with micrognathia were treated with interpositional arthroplasty and simultaneous DO and followed for a period of minimum 3 years. Preoperative, immediate postoperative, at the end of distraction, at 6 months and 3 years postdistraction consolidation radiographs were taken along with the clinical examination for mouth opening, deviation, length of the mandible and ramus, midline shift, occlusal cant, and occlusion. RESULTS: The results showed an increase in the mouth opening, length of the mandible and ramus height, correction of deviation, occlusion, and midline shift. Relapse was not seen in any case, rather one patient developed infection at the distractor site and two patients had fracture of the roots of the teeth at the osteotomy site. There was an overall improvement in the facial asymmetry. CONCLUSION: Simultaneous interpositional arthroplasty with DO should be used to correct TMJ ankylosis associated with facial asymmetry/micrognathia, as it reduces the need for second surgery, thereby saving the trauma of a second surgery and difficulty in intubation, increases the length of the mandible, corrects the deformity, thereby resulting in an acceptable facial esthetics and function. PMID- 27563612 TI - Autotransplantation donor tooth site harvesting using piezosurgery. AB - BACKGROUND: The harvesting of a tooth as a candidate for tooth autotransplantation requires that the delicate dental tissues around the tooth be minimally traumatized. This is especially so for the periradicular tissues of the tooth root and the follicular tissues surrounding the crown. The aim of this report is to describe the use of piezosurgery as an attempt at morbidity reduction in the harvesting of teeth for autotransplantation. METHODS: A piezosurgical handpiece and its selection of tips were easily adapted to allow the harvesting and delivery of teeth for autotransplantation purposes. RESULTS: Twenty premolar teeth were harvested using a piezosurgical device. The harvested teeth were subsequently successfully autotransplanted. All twenty teeth healed in a satisfactory manner without excessive mobility or ankyloses. CONCLUSIONS: Piezosurgery avoids some of the traumatic aspects of harvesting teeth and removing bone which are associated with thermal damage from the use of conventional rotary instruments or saws. Piezosurgery can be adapted to facilitate the predictable harvesting of teeth for autotransplantation purposes. PMID- 27563614 TI - Forgotten triangles of neck. AB - The purpose of this manuscript is to add some more information in the present scientific literature on these nearly forgotten triangles of surgical importance. The neck is an area that lends itself to anatomical geometry, such as triangles. Many triangles of the neck have been described, and some are well-known, yet, some have been nearly forgotten, i.e., Lesser's triangle, Farabeuf triangle, Pirogoff's triangle, and Beclard's triangle. From the anatomic and surgical point of view, the neck is an amazingly interesting place. It is like a connection where crucial functional units meet and pass. Added surgical landmarks are always helpful to the surgeon while dealing with the neck. Described triangles of neck in this article are always reliable and constant landmarks for head and neck surgeons. PMID- 27563613 TI - Success rate of implants placed in autogenous bone blocks versus allogenic bone blocks: A systematic literature review. AB - The aim of this study is to review and compare survival/success rate of dental implants inserted in autogenous and allogenic bone blocks (ALBs). A PubMed search was performed from January 1990 to June 2014 limited to English language and human studies. Studies that reported treatment outcome of implants inserted in augmented alveolar ridges with autogenous or ALBs were included. Primary search identified 470 studies. For autogenous bone block (ABB) 36 articles and for ALB 23 articles met the inclusion criteria. Evidence on implant survival/success rate of both techniques was limited to observational studies with relatively small sample sizes. Study design, treatment methods, follow-ups, defect location, and morphology varied among studies. The range of implant survival and success rates in ABB was from 73.8% to 100% and 72.8% to 100%, respectively. The corresponding numbers for ALB were 95.3-100% and 93.7-100%, respectively. A definite conclusion could not be reached. Future studies with long-term follow-ups are required to further elucidate this issue. PMID- 27563615 TI - Piezo harvesting of bone grafts from the anterior iliac crest: A technical note. AB - BACKGROUND: Autogenous bone graft harvesting from the iliac crest is associated with donor site morbidity. The aim of this report is to describe the use of piezosurgery as an attempt at morbidity reduction. MATERIALS AND METHODS: A piezosurgical handpiece and its selection of tips can easily be accommodated in an iliac crest wound to osteotomize and allow the harvest and delivery of autogenous bone grafts. RESULTS: Corticocancellous blocks or cancellous strips of autogenous bone can be readily harvested using a piezosurgical technique at the anterior iliac crest. CONCLUSION: Piezosurgery avoids some of the traumatic aspects of harvesting bone associated with the use of conventional rotary instruments or saws. PMID- 27563616 TI - Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction. AB - Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14 year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. PMID- 27563617 TI - Zurich pediatric distractor for ramal condylar unit distraction in temporomandibular joint ankylosis. AB - Temporomandibular joint (TMJ) Ankylosis is an extremely disabling condition characterized by difficulty or inability to open the mouth resulting in facial asymmetry, malocclusion and dental problems. Surgical excision of the ankylosed mass is the only treatment option available to gain mouth opening. The loss in vertical height of ramus following release of ankylosis is difficult to manage in both unilateral and bilateral TMJ ankylosis. Out of all the methods to restore this height Distraction Osteogenesis (DO) is gaining popularity because of predictable gain in the length without any associated morbidity. Recurrent bilateral TMJ ankylosis in a 32 year old male was treated by osteoarthrectomy and temporal fascia interpositioning arthroplasty. Bilateral reconstruction of ramal condylar unit (RCU) was carried out by Zurich paediatric distractor (KLS Martin, Tuttlingen Germany). Following a latency period of 7 days distraction was carried out at a rate of 1mm/day for 8 days. Distractors were removed after 12 weeks of consolidation period. The case was followed up for 12 months during which the mouth opening was maintained at 38 mm and there was no anterior open bite. PMID- 27563618 TI - The use of three-dimensional imaging to evaluate the effect of conventional orthodontic approach in treating a subject with facial asymmetry. AB - The growth of the craniofacial skeleton takes place from the 3(rd) week of intra uterine life until 18 years of age. During this period, the craniofacial complex is affected by extrinsic and intrinsic factors which guide or alter the pattern of growth. Asymmetry can be encountered due to these multifactorial effects or as the normal divergence of the hemifacial counterpart occurs. At present, an orthodontist plays a major role not only in diagnosing dental asymmetry but also facial asymmetry. However, an orthodontist's role in treating or camouflaging the asymmetry can be limited due to the severity. The aim of this research is to report a technique for facial three-dimensional (3D) analysis used to measure the progress of nonsurgical orthodontic treatment approach for a subject with maxillary asymmetry combined with mandibular angular asymmetry. The facial analysis was composed of five parts: Upper face asymmetry analysis, maxillary analysis, maxillary cant analysis, mandibular cant analysis, and mandibular asymmetry analysis which were applied using 3D software InVivoDental 5.2.3 (Anatomage Company, San Jose, CA, USA). The five components of the facial analysis were applied in the initial cone-beam computed tomography (T1) for diagnosis. Maxillary analysis, maxillary cant analysis, and mandibular cant analysis were applied to measure the progress of the orthodontics treatment (T2). Twenty-two linear measurements bilaterally and sixteen angular criteria were used to analyze the facial structures using different anthropometric landmarks. Only angular mandibular asymmetry was reported. However, the subject had maxillary alveolar ridge cant of 9.96 degrees and dental maxillary cant was 2.95 degrees in T1. The mandibular alveolar ridge cant was 7.41 degrees and the mandibular dental cant was 8.39 degrees . Highest decrease in the cant was reported maxillary alveolar ridge around 2.35 degrees and in the mandibular alveolar ridge around 3.96 degrees in T2. Facial 3D analysis is considered a useful adjunct in evaluating inter-arch biomechanics. PMID- 27563619 TI - The use of a dynamic real-time jaw tracking device and cone beam computed tomography simulation. AB - BACKGROUND: The aim was to introduce and preliminarily evaluate a new software application, SICAT Function, which can directly combine and merge three dimensional cone beam computed tomography (CBCT) and electronic SICAT jaw motion tracking (JMT) data. METHODS: A detailed description of the methods and dynamic clinical simulation of mandibular movements of a patient are demonstrated. Functional jaw movements on 3 days were recorded by JMT tracking system. The simulation was performed by merging CBCT and JMT data in the software SICAT Function suite. The condylar position simulated by SICAT Function suite was compared with real condyle position showed by a CBCT of the patient. RESULTS: The incisor ranges of functional movements were displayed by JMT tracking system. The visualization of patient-specific mandibular movement including the translation of the condyles was displayed after data merge. The recordings of mandibular movements of the patient were similar on 3 different days. The condylar position simulated by SICAT was coincident with real condyle position by CBCT data with the same amount of mouth opening. CONCLUSIONS: The SICAT Function software is a system capable of measuring and visualizing patient-specific jaw movement relative to the patient-specific anatomy of the jaw. Further studies are needed to validate its accuracy and its potential for future use. PMID- 27563620 TI - Gorlin-Goltz syndrome: An often missed diagnosis. AB - Gorlin-Goltz syndrome due to its high variability in expression are often not diagnosed as the syndrome and often managed same as that of odontogenic keratocyst. But a more careful approach for the syndrome is needed as there is high chance of malignant changes owing to improper management of the syndrome. In this manuscript a case report of Gorlin-Goltz syndrome with the diagnostic features of the same in Indian population along with the difference in treatment protocol from treating an odontogenic keratocyst is described with review of literature. PMID- 27563621 TI - A rare case of regression of brown tumors of tertiary hyperparathyroidism after parathyroidectomy and renal transplant: A 5-year follow-up. AB - Tertiary hyperparathyroidism (HPT) is a rare condition that affects patients with secondary HPT, which develop hyperplasia of the parathyroid glands, thus causing an increase in parathyroid hormone levels. Bone alterations are the main consequences of this condition including the development of osteolytic lesions called brown tumor. This article reports an unusual case of brown tumors located in the maxilla and mandible in a 19-year-old man with chronic renal failure with hyperplasia of the parathyroid glands. The lesions regressed approximately 5 months after the parathyroidectomy. At this same time, the patient underwent renal transplant. The patient was followed for 5 years, showing improvement in overall clinical status. There was also improvement of the results of laboratory tests and the pattern of trabecular bone. The correct diagnosis of oral lesions was of great relevance for the conservative treatment could have been chosen. PMID- 27563622 TI - A multidisciplinary approach to the management of temporomandibular joint ankylosis in a sickle-cell anemia patient in a resource-limited setting. AB - This report describes the multidisciplinary management of a 35-year-old female sickle-cell anemia patient who had unilateral bony ankylosis of the left temporomandibular joint secondary to septic arthritis. She was managed by a team comprising of maxillofacial surgeons, anesthetists, otorhinolaryngologist, and hematologist. Unilateral left interpositional arthroplasty and ipsilateral coronoidectomy through a postrami approach were done and followed by aggressive jaw physiotherapy in the postsurgical period. No perioperative morbidity was encountered. Mouth opening of 3.5 cm was achieved and maintained 7 months after surgery. Challenges and rationale for the use of a multidisciplinary team approach in treatment of such cases were discussed. PMID- 27563623 TI - Crouzon syndrome: Virtual planning of surgical treatment by application of internal distractors. AB - Crouzon syndrome is one of the frequent pathologies within craniosynostosis syndrome. Current progress in computers and biotechnologies allows improving surgical approach and forecasting final result of reconstruction as well. We present a case of successful surgical treatment of Crouzon syndrome, done by application of virtual planning allowing determining "monobloc" features, type of reconstruction and distraction protocol as well. A 20-year-old female had presented with craniofacial deformity. Clinical and radiological investigation revealed Crouzon syndrome. The "monobloc" creation, cranioplasty and internal distractors positioning, direction and schedule of advancement were done according to preoperative virtual planning data achieved by Materialise Mimics Research software. Nine months postoperative functional and esthetic result and radiological findings showed to be reasonable. That application of virtual simulation significantly allows to determine best direction of distraction and improves postoperative outcomes of surgical treatment of Crouzon syndrome. PMID- 27563624 TI - Congenital facial teratoma in a neonate: Surgical management and outcome. AB - Teratomas are among the most common tumors of childhood, but craniofacial teratomas are rare. They can be diagnosed antenatally. Craniofacial teratomas may cause airway obstruction in the newborn. We present a case of a newborn male child who was diagnosed to have a facial tumor in the 8(th) month of gestation. He was delivered normally and had no respiratory or feeding difficulties. He was also found to have a cleft palate. Serum alpha fetoprotein levels were normal. He underwent excision on day of life 9. At 11 months follow-up, he is well with no evidence of recurrence and good functional outcome. PMID- 27563625 TI - Metastatic clear cell variant of renal cell carcinoma of the mandible: Review and case report. AB - A case of metastatic renal cell carcinoma (RCC) to the mandible is reported. A 22 year-old man consulted us for hypoesthesia of the right lower lip. Panorama X-ray film showed a radiolucent lesion in the right mandibular body. A diagnosis of a metastatic tumor to the mandible from the right kidney was made after evaluation by computed tomography and bone scan with Tc99 methyl diphosphonate which also revealed multiple bone metastases. Histologically diagnosis was clear cell variant of RCC. Patient has been put on radiotherapy for symptomatic treatment and a molecularly targeted drug. The therapy effectively stopped the progressive growth of oral and other metastatic lesions. The quality of life is relatively well maintained with tolerable adverse effects. The patient is still on our follow-up with an improved quality of life. PMID- 27563626 TI - Papular elastorrhexis localized to the wrist, the intravenous infusion drip site. PMID- 27563627 TI - Aberrant Promoter Hypomethylation in CLL: Does It Matter for Disease Development? AB - Over the last 30 years, studies of aberrant DNA methylation in hematologic malignancies have been dominated by the primary focus of understanding promoter hypermethylation. These efforts not only resulted in a better understanding of the basis of epigenetic silencing of tumor suppressor genes but also resulted in approval of hypomethylating agents for the treatment of several malignancies, such as myelodysplastic syndrome and acute myeloid leukemia. Recent advances in global methylation profiling coupled with the use of mouse models suggest that aberrant promoter hypomethylation is also a frequent event in hematologic malignancies, particularly in chronic lymphocytic leukemia (CLL). Promoter hypomethylation affects gene expression and, therefore, may play an important role in disease pathogenesis. Here, we review recent findings and discuss the potential involvement of aberrant promoter hypomethylation in CLL. PMID- 27563628 TI - Association of E-selectin with hematological, hormonal levels and plasma proteins in children with end stage renal disease. AB - BACKGROUND: Hypercoagulable state is a common serious problem in patients with end-stage renal disease (ESRD). ESRD patients are in a condition of chronic inflammation. An increased level of E-selectin, "a key adhesion molecule that regulates leukocyte bindings to endothelium at damaged sites," accompanies the higher risk of inflammation in ESRD patients. We aimed to investigate the possible correlation among E-selectin as an adhesion molecule, coagulation factors, and inflammatory factors in children with ESRD. MATERIALS AND METHODS: Thirty-five child patients with ESRD who had been on regular dialysis treatment were registered in our study. Nighteen sex- and age-matched healthy volunteers were used as the control group. Laboratory tests were requested for the evaluation of hematological and biochemical parameters, and parathyroid hormone (PTH), and for coagulation state; fibrinogen, protein C, and protein S were measured. The enzyme-linked immunosorbent assay (ELISA) (Biomerica, CA, and IDS, UK). for serum E-selectin assay was provided by R and D Systems (Abingdon, UK). RESULTS: Hemoglubolin (Hb), blood urea nitrogen (BUN), creatinine, calcium, PTH, triglyceride (TG) concentrations in serum as well as E-selectin showed significant difference between the two study groups, as indeed was expected. Serum E-selectin was significantly higher (P value = 0.033) in dialysis patients than in healthy subjects. E-selectin was positively correlated only with phosphorus in ESRD children (r = 0.398, P = 0.018). No association was found for other parameters. CONCLUSION: Although in our study circulating E-selectin concentration "as an inflammatory maker" is independently positively associated with limited blood markers, for better evaluation, well-designed cohort studies should be examined in ESRD children. PMID- 27563629 TI - Diagnostic and prognostic significance of serum soluble endoglin levels in preeclampsia and eclampsia. AB - BACKGROUND: Preeclampsia is a multisystem disorder of unknown etiology that affects 4-5% of all pregnancies. The aim of the study was to evaluate the diagnostic accuracy of serum soluble endoglin (sEng) in preeclampsia and eclampsia and also to evaluate its prognostic significance. MATERIALS AND METHODS: This prospective case-control study carried out over a period of 1 year in the Department of Obstetrics and Gynaecology, King George Medical University, Lucknow. After written informed consent and ethical clearance, total 90 subjects were enrolled. Among them, 30 subjects of eclampsia, 15 of nonsevere preeclampsia, 15 of severe preeclampsia served as cases, and 30 healthy pregnant normotensive women served as controls. Levels were estimated by enzyme-linked immunosorbent assay technique in both cases and controls. RESULTS: Mean level was highest in eclampsia group (14.96 +/- 1.96 ng/mL) and lowest in controls (2.08 +/ 0.56 ng/mL). At cut-off value of sEng levels of >=6.26 ng/mL, it was found to be 100% sensitive and 100% specific for the diagnosis of preeclampsia (area under curve =1) at 95% confidence interval. sEng levels were strongly correlated with systolic (r = 0.928) and diastolic blood pressure (r = 0.916), serum lactate dehydrogenase (r = 0.791) and serum uric acid (r = 0.722). All four maternal deaths were reported within eclampsia group, in whom the mean sEng level was significantly higher (17.84 +/- 0.22) as compared to other subjects (9.50 +/- 5.80). CONCLUSION: sEng is a novel marker for diagnosis of preeclampsia, and it can also be used as a prognostic marker to predict the severity of preeclampsia. PMID- 27563630 TI - Effect of extracorporeal shock wave therapy on the treatment of patients with carpal tunnel syndrome. AB - BACKGROUND: The carpal tunnel syndrome (CTS) is the most common neuropathy. The aim of this study was to evaluate the effect of a new and noninvasive treatment including extracorporeal shock wave therapy (ESWT) in the treatment of CTS. MATERIALS AND METHODS: This study is a clinical trial conducted on 60 patients with moderate CTS in selected health centers of Isfahan Medical University from November 2014 to April 2015. Patients with CTS were randomly divided into two groups. Conservative treatment including wrist splint at night for 3 months, consumption of nonsteroidal anti-inflammatory drugs for 2 weeks, and oral consumption of Vitamin B1 for a month was recommended for both groups. The first group was treated with ESWT, one session per week for 4 weeks. Focus probe with 0.05, 0.07, 0.1, and 0.15 energy and shock numbers 800, 900, 1000, and 1100 were used from the first session to the fourth, respectively. The evaluated parameters were assessed before treatment and after 3 and 6 months. Data were analyzed using SPSS version 19, Student's t-test, and Chi-square test. RESULTS: All parameters were significantly decreased in the ESWT group after 3 months. These results remained almost constant after 6 months compared with 3 months after treatment. However, only two parameters considerably improved after 3 months of treatment in the control group. The entire indexes in the control group implicated the regression of results in long-term period. CONCLUSION: It is recommended to use ESWT as a conservative treatment in patients with CTS. PMID- 27563632 TI - Association between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in middle age patient with non-alcoholic fatty liver disease. AB - BACKGROUND: Liver biopsy is required to diagnose non-alcoholic steatohepatitis in patients with suspected non-alcoholic fatty liver disease (NAFLD). This study aimed to examine the relationship between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in patient with NAFLD. MATERIALS AND METHODS: In this cross-sectional study, a total of 180 patients, with an age range of 18-60 year old, with NAFLD based on ultrasonograghic findings were evaluated. Age, sex, body mass index, diabetes mellitus, hypertension, family history of liver disease and laboratory parameters recorded for all patients. Hence, grade of steatosis and stage of fibrosis were evaluated by liver biopsy. RESULTS: A total of 220 patients were enrolled. Liver biopsy was performed in 180 patients. Mean age was 43 +/- 10.6 years old and 66% were male. Ultrasonograghic findings showed mild, moderate and severe NAFLD was define in 100 (55.5%), 72 (40%) and 8 (4.5%) of patients, respectively. Liver biopsies showed that steatosis scores of <5%, 5-33% and 33-66% was define in 56 (31%), 116 (64%) and 9 (5%) of patients, respectively. Furthermore, fibrosis was defined as follow; none 92 (51%), mild 68 (38%), moderate 11 (6%), bridging 5 (3%) and cirrhosis 3 (2%) patients. There was no statistically significant relationship between ultrasonograghic findings and steatosis scores (P = 0.44), but statistically significant relationship was found between ultrasonograghic findings and fibrosis stage (P = 0.017). CONCLUSION: Findings revealed that, in patients with NAFLD, ultrasonographic finding were not in associate to steatosis, but were in relation with fibrosis stage. PMID- 27563631 TI - A comparison of outcome of medical and surgical treatment of migraine headache: In 1 year follow-up. AB - BACKGROUND: This study was designed to compare the efficacy of the medical treatment versus the surgical treatment approach to decompression of trigger point nerves in patients with migraine headaches. MATERIALS AND METHODS: Fifty volunteers were randomly assigned to the medical treatment group (n = 25) or the surgical treatment group (n = 25) after examination by the team neurologist to ensure a diagnosis of migraine headache. All patients received botulinum toxin type A to confirm the trigger sites. The surgical treatment group underwent surgical deactivation of the trigger site(s). The medical treatment group underwent prophylactic pharmacologic interventions by the neurologist. Pretreatment and 12-month posttreatment migraine headache frequency, duration, and intensity were analyzed and compared to determine the success of the treatments. RESULTS: Nineteen of the 25 patients (76%) in the surgical treatment group and 10 of the 25 patients (40%) in the medical treatment group experienced a successful outcome (at least a 50% decrease in migraine frequency, duration, or intensity) after 1 year from surgery. Surgical treatment had a significantly higher success rate than medical treatment (P < 0.001). Nine patients (36%) in the surgical treatment group and one patient (4%) in the medical treatment group experienced cessation of migraine headaches. The elimination rate was significantly higher in the surgical treatment group than in the medical treatment group (P < 0.001). CONCLUSIONS: Based on the 1-year follow-up data, there is strong evidence that surgical manipulation of one or more migraine trigger sites can successfully eliminate or reduce the frequency, duration, and intensity of migraine headaches in a lasting manner. PMID- 27563633 TI - Protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments in ovariectomized rats. AB - BACKGROUND: Regarding the anti-oxidative effects on the central nervous system, the possible protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments was investigated in ovariectomized (OVX) rats. MATERIALS AND METHODS: The OVX rats treated by (1) vehicle, (2) scopolamine, and (3-4) scopolamine plus estradiol (20 or 20 or 60 MUg/kg). Estradiol was administered (20 or 60 MUg/kg, intraperitoneally) daily for 6 weeks after ovariectomy. The rats were examined for learning and memory using passive avoidance test. Scopolamine (2 mg/kg) was injected 30 min after training in the test. The brains were then removed to determine malondialdehyde (MDA) and thiol contents. RESULTS: Scopolamine shortened the time latency to enter the dark compartment in (P < 0.01). Compared to scopolamine, pretreatment by both doses of estradiol prolonged the latency to enter the dark compartment (P < 0.01). The brain tissues MDA concentration as an index of lipid peroxidation was decreased (P < 0.05). Pretreatment by estradiol lowered the concentration of MDA, while it increased thiol content compared to scopolamine (P < 0.05 and P < 0.01). CONCLUSIONS: These results allow us to suggest a protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments in OVX rats. PMID- 27563634 TI - Antibiotic resistance pattern and evaluation of metallo-beta lactamase genes (VIM and IMP) in Pseudomonas aeruginosa strains producing MBL enzyme, isolated from patients with secondary immunodeficiency. AB - BACKGROUND: One of the most common causes of hospital-acquired secondary infections in hospitalized patients is Pseudomonas aeruginosa. The aim of this study is to evaluate the expression of IMP and VIM in Pseudomonas aeruginosa strains (carbapenem resistant and producer MBL enzyme) in patients with secondary immunodeficiency. MATERIALS AND METHODS: In a cross sectional study, 96 patients with secondary immunodeficiency hospitalized in the Al-Zahra hospital were selected. Carbapenem resistant strains isolated and modified Hodge test was performed in order to confirm the presence of the metallo carbapenemase enzyme. Under the standard conditions they were sent to the central laboratory for investigating nosocomial infection Multiplex PCR. RESULTS: Of 96 samples 28.1% were IMP positive, 5.2% VIM positive and 3.1% both VIM and IMP positive. The prevalence of multidrug resistance in the IMP and/or VIM negative samples was 29%, while all 5 VIM positive samples have had multidrug resistance. Also the prevalence of multi-drug resistance in IMP positive samples were 96.3% and in IMP and VIM positive samples were 100%. According to Fisher's test, the prevalence of multi-drug resistance based on gene expression has significant difference (P < 0.001). CONCLUSION: Based on the results of this study it can be concluded that, a significant percentage of patients with secondary immunodeficiency that suffer nosocomial infections with multidrug resistance, especially Pseudomonas aeruginosa, are probably MBL-producing gene positive. Therefore the cause of infection should be considered in the hospital care system to identify their features, the presence of genes involved in the development of multi-drug resistance and antibiotic therapy. PMID- 27563635 TI - The comparison between modified kligman formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation. AB - BACKGROUND: Post inflammatory hyperpigmentation (PIH) is a common problem occurs following many dermatologic diseases and medical interventions. Different modalities including topical agents, lasers and intense pulsed light (IPL) are suggested for treatment of the post-burn PIH. In the current study, we evaluated the efficacy of IPL plus modified Kligman cream (MODIFIED KLIGMAN CREAM) versus MODIFIED KLIGMAN CREAM alone in the treatment of the post-burn PIH. MATERIALS AND METHODS: This was a randomized, non-blinded clinical trial. A total of 53 patches of post-burn PIP in 14 patients were randomized to receive either two sessions of IPL plus modified Kligman formula or kligman formula for 2 months. The patients were recommended to apply MODIFIED KLIGMAN CREAM cream for 12 h at night. RESULTS: According to our results, the patients in the MODIFIED KLIGMAN CREAM + IPL group had higher satisfaction as compared with MODIFIED KLIGMAN CREAM alone (P = 0.000) (Mann-Whitney test). In addition, according to physician evaluation, the patients in the MODIFIED KLIGMAN CREAM + IPL group had higher satisfaction as compared with MODIFIED KLIGMAN CREAM alone (P = 0.000) (Mann-Whitney test). No side effects except a little irritation, erythema and exfoliation due to MODIFIED KLIGMAN CREAM cream were seen in the patients. CONCLUSIONS: The results of our study showed the better efficacy and faster response of the IPL plus modified Kligman formula versus modified Kligman formula in the treatment of the post-burn PIH. To better determine the efficacy of IPL in treatment of the post-burn PIP, more extensive studies as randomized, double-blinded clinical trial are recommended. PMID- 27563636 TI - In vivo/In vitro immune responses to L. major isolates from patients with no clinical response to Glucantime. AB - BACKGROUND: Leishmaniasis is a major health problem in some endemic areas of tropical and subtropical areas of the world. Interleukin-12 (IL-12) and interferon gamma (IFN-gamma) are essential cytokines associated with initiation of Th1 response. The main objective of this study was to evaluate of the type of immune response to L. major isolates from patients with no clinical response to antimonite (Glucantime). MATERIALS AND METHODS: This experimental study was carried out during 2013-2014. In the current study Leishmania major were isolated from 10 CL patients with a history of at least one course of treatment with Meglumine antimonate (Sb5). The isolates were used to evaluate in vitro and in vivo response to Sb5. J774 murine macrophage cell line was used for in vitro tests and Balb/c mice was used for in vivo studies. IL-12 gene expression was evaluated using Real-time PCR and IFN-gamma serum level was quantified using ELISA technique. SPSS (version: 20), analysis of Covariance (ANCOVA) was used for statistical analysis. RESULTS: PCR results confirmed that all 10 isolates were L. major. The mean of IL-12 gene expression in vitro, in vivo and IFN-gamma serum levels (pg/ml) after 2 and 3 weeks treatment in vivo, increased significantly following the treatment with Glucantime in the two groups of Balb/c mice infected either with patients' isolates or standard L. major. No significant difference was seen between the patients' isolates and standard species. CONCLUSIONS: Although the L. major were isolated from patients with active lesion and no clinical response to Glucantime after at least one courses of Glucantime treatment but in vivo and in vitro immune response of L. major isolates showed no difference between the patients' isolates and standard L. major. PMID- 27563637 TI - Leptin serves as angiogenic/mitogenic factor in melanoma tumor growth. AB - BACKGROUND: Tumor development is angiogenesis dependent. There is evidence that leptin contributes to tumor growth. However, all the mechanisms by which leptin does this has not been clearly established. The objective of the present study was to test the hypothesis that leptin enhances melanoma tumor growth through inducing angiogenesis and cell proliferation. MATERIALS AND METHODS: We injected 2 * 10(6) B16F10 melanoma cells subcutaneously to 32 C57BL6 mice. The mice were randomly divided into four groups of eight animals, on day 8. Two groups received twice daily intraperitoneal (i.p.) injections of either phosphate buffered saline or recombinant murine leptin (1 MUg/g initial body weight). Two groups received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 MUg/injection every 3 consecutive days. By the end of the 2(nd) week, the animals were euthanized and blood samples and tumors were analyzed. Angiogenesis and proliferation were assessed by immunohistochemical staining for CD31 and Ki-67 respectively. RESULTS: Tumors size, capillary density, plasma levels of vascular endothelial growth factor, and the number of Ki-67-positive stained cells were significantly more in the leptin than 9F8 and both control groups (P < 0.05). CONCLUSION: Taken together, our findings reinforce the idea that leptin acts as an angiogenic and mitogenic factor to promote melanoma growth. PMID- 27563638 TI - Trend and manifestations of falciparum malaria in a tertiary care hospital of India. AB - BACKGROUND: The recent focus is on the increase in the burden of falciparum cases with a varied spectrum of presentation and outcome, especially in developing countries like India. This study was undertaken to analyze the trend and manifestations of falciparum malaria in a tertiary care hospital. MATERIALS AND METHODS: This descriptive study was carried out at the Gauhati Government Medical College and Hospital from June 2006 to May 2007. The data were collected on demographic and time characteristics, clinical and laboratory findings, the outcome of disease and expressed in proportion or percentages. RESULTS: Out of the 100 cases, around 2(nd)/3(rd) (63%) of cases were in the age group of 15-30 years and the mean age was found to be 29.51 years. About 66% of them were males. Clinical presentations included pain abdomen (42, 42%), nausea and vomiting (35, 35%), jaundice (34, 34%), oliguria (24, 24%), altered sensorium (24, 24%), breathing difficulty (10, 10%), and seizures (5, 5%). Number of cases and mortality were more with a peak in the month of May and September. Manifestations of severe falciparum malaria included hepatopathy (38%), renal failure (28%), shock (9%), acute respiratory distress syndrome (7%), hypoglycemia (3%), and severe anemia (1%). Eighty-two cases (82%) recovered and 18 cases (18%) expired. CONCLUSION: Falciparum malaria is more among younger adult age group and males. Complications and mortality are also more due to falciparum malaria. PMID- 27563640 TI - Design, formulation, and evaluation of ginger medicated chewing gum. AB - BACKGROUND: Various ginger compounds improve gastrointestinal problems and motion sickness. The main effects of ginger allocate to some phenolics such as gingerols and shogaols that act as their active agents. Chewing gums are among convenient dosage forms which patients prefer due to their advantages. Hence, this study tried to design, formulate, and evaluate ginger chewing gum of favorable taste and texture to avoid motion sickness and have gastro-protective and anti-oxidant effect. MATERIALS AND METHODS: Dried ginger rhizomes were percolated to extract ginger compounds. Total phenolics were measured in 70% hydro-alcoholic extract of ginger by gallic and tannic acid standards using Folin-Ciocalteu's reagent. Chewing gums containing 50 mg of concentrated extract were prepared. Content uniformity, weight variation, release pattern, organoleptic, and mechanical properties were evaluated. RESULTS: Phenolic content was measured 61.50 +/- 5.27 mg/g and 76.75 +/- 5.45 mg/g of concentrated extract as gallic acid and tannic acid equivalents, respectively. Release pattern of formulations with different gum bases and sweeteners demonstrated almost 100% release of drug. Evaluation of organoleptic properties was on 10 healthy volunteers and later prepared formulations exhibited better characteristics. Formulations without any flavorants have higher acceptability. Evaluation of mechanical properties showed higher stiffness of F15. CONCLUSION: Ginger chewing gum comprises admissible properties to be used as a modern drug delivery system due to its advantageous results in motion sickness. It passed all the specified tests for an acceptable chewing gum. Thus, it may be successfully produced to help GI problems. PMID- 27563639 TI - Expression of microRNA-370 in human breast cancer compare with normal samples. AB - BACKGROUND: Breast cancer is the second leading cause of deaths from cancer in the woman. MicroRNAs (miRNAs) are endogenous noncoding RNAs that are known critical player in carcinogenesis. The role of miR-370 in malignancies remains controversial because of its levels varying in different cancers according to its targets while the role of miR-370 in breast cancer has not been addressed so far. The aim of this study was to identify the expression pattern of miR-370 in human breast cancer tissue compared to adjacent healthy tissue. MATERIALS AND METHODS: Twenty-two fresh frozen tissues (normal and malignant) from patients with breast cancer were examined for miR-370 by quantitative real-time polymerase chain reaction method at 2013. RESULTS: We observed up-regulation (six-fold higher) of miR-370 in breast cancer tissue compared with normal adjacent tissue. Tumor samples in stage III, invasive ductal type, larger tumor size, human epidermal growth-factor receptor 2+, estrogen receptor/progesterone receptor-, P53 - status showed significantly increased expression in miR-370. CONCLUSION: Together, miR 370 may acts as an onco-miRNA, and it may have a novel role in breast cancer. Detection of miR-370 and its targets could be helpful as a diagnostic biomarker and therapeutic target. PMID- 27563641 TI - Program and Abstracts from the Canadian Digestive Diseases WeekTM 2016. PMID- 27563642 TI - Power Imbalances, Food Insecurity, and Children's Rights in Canada. AB - Increasingly, food is provided through an industrial food system that separates people from the source of their food and results in high rates of food insecurity, particularly for the most vulnerable in society. A lack of food is a symptom of a lack of power in a system that privileges free market principles over social justice and the protection of human rights. In Canada, the high rates of food insecurity among Canadian children is a reflection of their lack of power and the disregard of their human rights, despite the adoption of the United Nations (UN) Convention on the Rights of the Child in 1991 and ratification of the International Covenant on Social, Economic and Cultural Rights in 1976, which established the right to food for all Canadians. Dueling tensions between human rights and market forces underpin this unacceptable state of affairs in Canada. Gaventa's "power cube" that describes different facets of power - including spaces, levels, and forms - is used to help understand the power imbalances that underlie this injustice. The analysis considers the impact of neoliberal free market principles on the realization of human rights, and the negative impacts this can have on health and well-being for the most vulnerable in society. Canadian case studies from both community organizations provide examples of how power can be shifted to achieve more inclusive, rights-based policy and action. Given increased global pressures toward more open trade markets and national austerity measures that hollow out social supports, Canada provides a cautionary tale for countries in the EU and the US, and for overall approaches to protect the most vulnerable in society. PMID- 27563643 TI - Corrigendum: Voice Pathology Detection Using Modulation Spectrum-Optimized Metrics. AB - [This corrects the article on p. 1 in vol. 4, PMID: 26835449.]. PMID- 27563645 TI - DNA-Binding Proteins Regulating pIP501 Transfer and Replication. AB - pIP501 is a Gram-positive broad-host-range model plasmid intensively used for studying plasmid replication and conjugative transfer. It is a multiple antibiotic resistance plasmid frequently detected in clinical Enterococcus faecalis and Enterococcus faecium strains. Replication of pIP501 proceeds unidirectionally by a theta mechanism. The minimal replicon of pIP501 is composed of the repR gene encoding the essential rate-limiting replication initiator protein RepR and the origin of replication, oriR, located downstream of repR. RepR is similar to RepE of related streptococcal plasmid pAMbeta1, which has been shown to possess RNase activity cleaving free RNA molecules in close proximity of the initiation site of DNA synthesis. Replication of pIP501 is controlled by the concerted action of a small protein, CopR, and an antisense RNA, RNAIII. CopR has a dual function: It acts as transcriptional repressor at the repR promoter and, in addition, prevents convergent transcription of RNAIII and repR mRNA (RNAII), which indirectly increases RNAIII synthesis. CopR binds asymmetrically as a dimer at two consecutive binding sites upstream of and overlapping with the repR promoter. RNAIII induces transcriptional attenuation within the leader region of the repR mRNA (RNAII). Deletion of either control component causes a 10- to 20 fold increase of plasmid copy number, while simultaneous deletions have no additional effect. Conjugative transfer of pIP501 depends on a type IV secretion system (T4SS) encoded in a single operon. Its transfer host-range is considerably broad, as it has been transferred to virtually all Gram-positive bacteria including Streptomyces and even the Gram-negative Escherichia coli. Expression of the 15 genes encoding the T4SS is tightly controlled by binding of the relaxase TraA, the transfer initiator protein, to the operon promoter overlapping with the origin of transfer (oriT). The T4SS operon encodes the DNA-binding proteins TraJ (VirD4-like coupling protein) and the VirB4-like ATPase, TraE. Both proteins are actively involved in conjugative DNA transport. Moreover, the operon encodes TraN, a small cytoplasmic protein, whose specific binding to a sequence upstream of the oriT nic-site was demonstrated. TraN seems to be an effective repressor of pIP501 transfer, as conjugative transfer rates were significantly increased in an E. faecalis pIP501DeltatraN mutant. PMID- 27563646 TI - Ruminal Fermentation of Anti-Methanogenic Nitrate- and Nitro-Containing Forages In Vitro. AB - Nitrate, 3-nitro-1-propionic acid (NPA) and 3-nitro-1-propanol (NPOH) can accumulate in forages and be poisonous to animals if consumed in high enough amounts. These chemicals are also recognized as potent anti-methanogenic compounds, but plants naturally containing these chemicals have been studied little in this regard. Presently, we found that nitrate-, NPA-, or NPOH containing forages effectively decreased methane production, by 35-87%, during in vitro fermentation by mixed cultures of ruminal microbes compared to fermentation by cultures incubated similarly with alfalfa. Methane production was further decreased during the incubation of mixed cultures also inoculated with Denitrobacterium detoxificans, a ruminal bacterium known to metabolize nitrate, NPA, and NPOH. Inhibition of methanogens within the mixed cultures was greatest with the NPA- and NPOH-containing forages. Hydrogen accumulated in all the mixed cultures incubated with forages containing nitrate, NPA or NPOH and was dramatically higher, exceeding 40 MUmol hydrogen/mL, in mixed cultures incubated with NPA-containing forage but not inoculated with D. detoxificans. This possibly reflects the inhibition of hydrogenase-catalyzed uptake of hydrogen produced via conversion of 50 MUmol added formate per milliliter to hydrogen. Accumulations of volatile fatty acids revealed compensatory changes in fermentation in mixed cultures incubated with the nitrate-, NPA-, and NPOH-containing forages as evidenced by lower accumulations of acetate, and in some cases, higher accumulations of butyrate and lower accumulations of ammonia, iso-buytrate, and iso-valerate compared to cultures incubated with alfalfa. Results reveal that nitrate, NPA, and NPOH that accumulate naturally in forages can be made available within ruminal incubations to inhibit methanogenesis. Further research is warranted to determine if diets can be formulated with nitrate-, NPA-, and NPOH containing forages to achieve efficacious mitigation in ruminant methane emissions without adversely affecting fermentative efficiency or risking toxicity to animals. PMID- 27563647 TI - Overview of advances in cancer immunotherapy. PMID- 27563644 TI - Replisome Assembly at Bacterial Chromosomes and Iteron Plasmids. AB - The proper initiation and occurrence of DNA synthesis depends on the formation and rearrangements of nucleoprotein complexes within the origin of DNA replication. In this review article, we present the current knowledge on the molecular mechanism of replication complex assembly at the origin of bacterial chromosome and plasmid replicon containing direct repeats (iterons) within the origin sequence. We describe recent findings on chromosomal and plasmid replication initiators, DnaA and Rep proteins, respectively, and their sequence specific interactions with double- and single-stranded DNA. Also, we discuss the current understanding of the activities of DnaA and Rep proteins required for replisome assembly that is fundamental to the duplication and stability of genetic information in bacterial cells. PMID- 27563648 TI - Harnessing the immune system to improve cancer therapy. AB - Cancer immunotherapy uses the immune system and its components to mount an anti tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments. Prominent examples of passive immunotherapy include administration of monoclonal antibodies and cytokines and adoptive cell transfer of ex vivo "educated" immune cells. Active immunotherapy refers, among others, to anti-cancer vaccines [peptide, dendritic cell (DC)-based and allogeneic whole cell vaccines], immune checkpoint inhibitors and oncolytic viruses, whereas new approaches that can further enhance anti-cancer immune responses are also widely explored. Herein, we present the most popular cancer immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure. PMID- 27563649 TI - Neoantigen-based cancer immunotherapy. AB - Emerging clinical evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy in all cancer types. Recent clinical data clearly demonstrated that human tumor cells express antigenic peptides (epitopes) that can be recognized by autologous tumor-specific T cells and that enhancement of such immune reactivity can potentially lead to cancer control and cancer regression in patients with advanced disease. However, in most cases, it is unclear which tumor antigens (Ags) mediated cancer regression. Mounting evidence indicates that numerous endogenous mutated cancer proteins, a hallmark of tumor cells, can be processed into peptides and presented on the surface of tumor cells, leading to their immune recognition in vivo as "non-self" or foreign. Massively parallel sequencing has now overcome the challenge of rapidly identifying the comprehensive mutational spectrum of individual tumors (i.e., the "mutanome") and current technologies, as well as computational tools, have emerged that allow the identification of private epitopes derived from their mutanome and called neoantigens (neoAgs). On this basis, both CD4(+) and CD8(+) neoantigen-specific T cells have been identified in multiple human cancers and shown to be associated with a favorable clinical outcome. Notably, emerging data also indicate that neoantigen recognition represents a major factor in the activity of clinical immunotherapies. In the post-genome era, the mutanome holds promise as a long-awaited 'gold mine' for the discovery of unique cancer cell targets, which are exclusively tumor-specific and unlikely to drive immune tolerance, hence offering the chance for highly promising clinical programs of cancer immunotherapy. PMID- 27563650 TI - Towards tumor immunodiagnostics. AB - Immunodiagnostic markers applicable on tissue or cytologic material may be prognostic or predictive of response to immunomodulatory drugs and may also be classified according to whether they are cell-specific or tumor-tissue-specific. Cell-specific markers are evaluated under the microscope as (I) morphological, corresponding to the assessment of tumor infiltrating immune cells on routine hematoxylin & eosin (H&E) sections; and (II) immunophenotypic, including the immunohistochemical (IHC) assessment of markers characteristic for tumor infiltrating immune cells. Tumor-tissue-specific markers are assessed in tissue extracts that may be enriched in neoplastic cells but almost inevitably also contain stromal and immune cells infiltrating the tumor. Such markers include (I) immune-response-related gene expression profiles, and (II) tumor genotype characteristics, as recently assessed with large-scale genotyping methods, usually next generation sequencing (NGS) applications. Herein, we discuss the biological nature of immunodiagnostic markers, their potential clinical relevance and the shortcomings that have, as yet, prevented their clinical application. PMID- 27563651 TI - DNA damage, tumor mutational load and their impact on immune responses against cancer. AB - Advances in immunotherapy have changed the therapeutic landscape in many malignancies. Immune checkpoint inhibitors have already received regulatory approval in melanomas, lung, renal and bladder carcinomas. A common feature of these neoplasms is the increased mutational load, related to a possible increase number of tumor neoantigens that are recognized by the immune system. The mechanisms that DNA damage could confer to the mutational load and the formation of neoantigens and how this could be exploited to advance our immunotherapeutic strategies is discussed in this review. PMID- 27563652 TI - The dual role of complement in cancer and its implication in anti-tumor therapy. AB - Chronic inflammation has been linked to the initiation of carcinogenesis, as well as the advancement of established tumors. The polarization of the tumor inflammatory microenvironment can contribute to either the control, or the progression of the disease. The emerging participation of members of the complement cascade in several hallmarks of cancer, renders it a potential target for anti-tumor treatment. Moreover, the presence of complement regulatory proteins (CRPs) in most types of tumor cells is known to impede anti-tumor therapies. This review focuses on our current knowledge of complement's potential involvement in shaping the inflammatory tumor microenvironment and its role on the regulation of angiogenesis and hypoxia. Furthermore, we discuss approaches using complement-based therapies as an adjuvant in tumor immunotherapy. PMID- 27563653 TI - Optimized tumor cryptic peptides: the basis for universal neo-antigen-like tumor vaccines. AB - The very impressive clinical results recently obtained in cancer patients treated with immune response checkpoint inhibitors boosted the interest in immunotherapy as a therapeutic choice in cancer treatment. However, these inhibitors require a pre-existing tumor specific immune response and the presence of tumor infiltrating T cells to be efficient. This immune response can be triggered by cancer vaccines. One of the main issues in tumor vaccination is the choice of the right antigen to target. All vaccines tested to date targeted tumor associated antigens (TAA) that are self-antigens and failed to show a clinical efficacy because of the immune self-tolerance to TAA. A new class of tumor antigens has recently been described, the neo-antigens that are created by point mutations of tumor expressing proteins and are recognized by the immune system as non-self. Neo-antigens exhibit two main properties: they are not involved in the immune self-tolerance process and are immunogenic. However, the majority of the neo antigens are patient specific and their use as cancer vaccines requires their previous identification in each patient individualy that can be done only in highly specialized research centers. It is therefore evident that neo-antigens cannot be used for patient vaccination worldwide. This raises the question of whether we can find neo-antigen like vaccines, which would not be patient specific. In this review we show that optimized cryptic peptides from TAA are neo antigen like peptides. Optimized cryptic peptides are recognized by the immune system as non-self because they target self-cryptic peptides that escape self tolerance; in addition they are strongly immunogenic because their sequence is modified in order to enhance their affinity for the HLA molecule. The first vaccine based on the optimized cryptic peptide approach, Vx-001, which targets the widely expressed tumor antigen telomerase reverse transcriptase (TERT), has completed a large phase I clinical study and is currently being tested in a randomized phase II trial in non-small cell lung cancer (NSCLC) patients. PMID- 27563654 TI - The European Organization for Research and Treatment of Cancer perspective on designing clinical trials with immune therapeutics. AB - Cancer immunotherapy has had a major impact on the established paradigms of drug development and clinical trial research. The innovative mechanism of action of these compounds has resulted in new patterns of response and safety profiles, which pose challenges for the classical trial methodology. In this review we report on the search for the maximum tolerated dose, the recommended phase II dose and the appropriate target population in phase I trials. We provide some statistical considerations on the choice of endpoints for phase II and III trials and the limitations of frequently used trial designs in the presence of a delayed treatment effect, which may be induced by the immune modulating effect of the checkpoint inhibitors. We summarize the currently available data on the safety profile of these new compounds, which can guide protocol safety recommendations. Finally, we report on the current evidence of biomarker development. PMID- 27563655 TI - Immunotherapy in non-small cell lung cancer: the clinical impact of immune response and targeting. AB - Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. In recent years, through a better understanding of the interactions between the immune system and tumor cells (TC), immunotherapy has emerged as a promising therapeutic strategy. Chemotherapy has long been reported to interfere with the immune response to the tumor and conversely, anti-tumor immunity may add to those effects. Anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, tumor cell vaccines and dendritic cell (DC) vaccines emerged as potent inducers of the immune response against the tumor. More recently the approval of the anti-programmed cell death 1 (anti-PD-1) monoclonal antibodies nivolumab and pembrolizumab for previously treated advanced squamous and non-squamous NSCLC, as well as other immune checkpoint inhibitors delivering promising results, has radically transformed the therapeutic landscape of NSCLC. Combination strategies now appear as the next step. Notwithstanding these successes, immunotherapy still holds significant drawbacks and currently several improvements are needed before routine use in clinical practice, including identification of robust biomarkers for optimal patient selection, as well as defining the best way to evaluate response. PMID- 27563657 TI - Immunobiology and immunotherapy in genitourinary malignancies. AB - Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guerin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo. The immune checkpoint inhibitor nivolumab (anti-PD-1) recently received FDA approval for the management of patients with advanced RCC patients previously treated with anti-angiogenic therapy, based on OS benefit compared to everolimus. Recently, large clinical trials demonstrated meaningful clinical benefit, including durable responses, as well as a good tolerability/safety profile with the use of immune checkpoint inhibitors in advanced RCC and chemotherapy-resistant advanced urothelial carcinoma (UC), while FDA just approved atezolizumab for platinum-treated advanced UC. Numerous interesting trials in different cancers are ongoing. Several combinations of immune checkpoint blockade with chemotherapeutics, vaccines, targeted tyrosine kinase inhibitors & monoclonal antibodies, epigenetic modifiers, anti-angiogenic agents, tumor microenvironment & myeloid cell targeting therapies, metabolic modification strategies, radiation, and others, are being tested in clinical trials. Comprehensive understanding of the factors underlying antitumor immune responses in physiologically relevant animal models and humans will refine further the clinical benefit of immunotherapy. Discovery and validation of appropriate molecular biomarkers via coordinated translational research efforts, rational clinical trial designs with suitable endpoints and well-defined eligibility criteria, prospective registries/databases, careful evaluation of cost-effectiveness and safety/tolerability, adequate funding and open continuous discussions among all stakeholders will support the revolutionary nature of immunotherapy in GU cancers. PMID- 27563656 TI - Melanoma immunotherapy dominates the field. AB - The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID- 27563658 TI - The significance of tumor-associated immune response in molecular taxonomy, prognosis and therapy of colorectal cancer patients. AB - The importance of host immune response in colorectal cancer (CRC) has been constantly revealed through the last 10 years. A number of relevant immune markers have been introduced as prognostic and are now been used alone or in combination with each other in clinical practice. Efforts establishing a worldwide consensus on the implications of immune-profiles in conjunction to other factors are designed in the right direction in order to more effectively categorize patients with CRC in groups that might benefit from currently used or future applied therapies. On the other hand, a number of clinical trials have evolved the application of immunotherapies in patients with CRC both in the adjuvant and palliative setting. PMID- 27563660 TI - Future perspectives in cancer immunotherapy. AB - The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors. In particular, immune check-point inhibition in melanoma, non-small-cell lung cancer and renal cancer, peptide vaccination in prostate cancer and glioblastoma, and oncolytic immunotherapy in melanoma are well-established therapeutic modalities that have obtained approval by regulatory authorities and are already in clinical use. A large number of ongoing clinical trials involving thousands of patients are currently seeking to define the appropriate tumor type, therapeutic setting, treatment combination and patient populations in order to maximize clinical benefit from immunotherapeutic agents. In this context, identification of the patients whose tumors are most likely to respond to immunotherapy by the use of appropriate biomarkers will be crucial for the optimal implementation of immunotherapy into the therapeutic armamentarium. PMID- 27563659 TI - Toxicity management of immunotherapy for patients with metastatic melanoma. AB - Checkpoint inhibitors have revolutionized the treatment of patients with metastatic melanoma offering improved responses and significant survival benefit. These agents are now approved for the treatment of metastatic melanoma, squamous and non-squamous non-small cell lung cancer (NSCLC) and kidney cancer, while they are now being investigated in a range of other malignancies. In addition, another anti-PD-L1 monoclonal antibody (atezolizumab) was recently approved for urothelial cancer. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody and the anti-PD-1 agents nivolumab and pembrolizumab have followed large clinical development programs, therefore, information regarding their safety and toxicity profile is readily available. Unique toxicities have been observed, which stem from and relate to the immune activation by these agents and are thus termed as immune-related adverse events (irAEs). Clinicians and patients should be aware of this different toxicity profile, so as to promptly recognize, identify and manage symptoms related to irAEs. Indeed, clinical experience has shown that these immune events, when they are early recognized and timely managed, are mostly reversible otherwise they can evoke severe or even life-threatening situations. Several recommendations and guidelines have been developed for the management of irAEs and algorithms have been published based primarily on our knowledge from the ipilimumab trials. PMID- 27563661 TI - Therapeutic Strategies in HCC: Radiation Modalities. AB - Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID- 27563662 TI - Expression of miRNA-122 Induced by Liver Toxicants in Zebrafish. AB - MicroRNA-122 (miRNA-122), also known as liver-specific miRNA, has recently been shown to be a potent biomarker in response to liver injury in mammals. The objective of this study was to examine its expression in response to toxicant treatment and acute liver damage, using the zebrafish system as an alternative model organism. For the hepatotoxicity assay, larval zebrafish were arrayed in 24 well plates. Adult zebrafish were also tested and arrayed in 200 mL cages. Animals were exposed to liver toxicants (tamoxifen or acetaminophen) at various doses, and miRNA-122 expression levels were analyzed using qRT-PCR in dissected liver, brain, heart, and intestine, separately. Our results showed no significant changes in miRNA-122 expression level in tamoxifen-treated larvae; however, miRNA 122 expression was highly induced in tamoxifen-treated adults in a tissue specific manner. In addition, we observed a histological change in adult liver (0.5 MUM) and cell death in larval liver (5 MUM) at different doses of tamoxifen. These results indicated that miRNA-122 may be utilized as a liver-specific biomarker for acute liver toxicity in zebrafish. PMID- 27563663 TI - A Gram-Negative Bacterial Secreted Protein Types Prediction Method Based on PSI BLAST Profile. AB - Prediction of secreted protein types based solely on sequence data remains to be a challenging problem. In this study, we extract the long-range correlation information and linear correlation information from position-specific score matrix (PSSM). A total of 6800 features are extracted at 17 different gaps; then, 309 features are selected by a filter feature selection method based on the training set. To verify the performance of our method, jackknife and independent dataset tests are performed on the test set and the reported overall accuracies are 93.60% and 100%, respectively. Comparison of our results with the existing method shows that our method provides the favorable performance for secreted protein type prediction. PMID- 27563664 TI - The Modulatory Effect of Ischemia and Reperfusion on Arginine Vasopressin-Induced Arterial Reactions. AB - Aim of the Study. The purpose of this study was to investigate the impact of ischemia and reperfusion on the resistance of arteries to AVP (arginine vasopressin), with a particular emphasis on the role of smooth muscle cells in the action of vasopressin receptors and the role of the cGMP-associated signalling pathway. Materials and Methods. Experiment was performed on the perfunded tail arteries from male Wistar rats. The constriction triggered by AVP after 30 minutes of ischemia and 30 and 90 minutes of reperfusion was analysed. Analogous experiments were also carried out in the presence of 8Br-cGMP. Results. Ischemia reduces and reperfusion increases in a time-dependent manner the arterial reaction to AVP. The presence of 8Br-cGMP causes a significant decrease of arterial reactivity under study conditions. Conclusions. Ischemia and reperfusion modulate arterial contraction triggered by AVP. The effect of 8Br cGMP on reactions, induced by AVP after ischemia and reperfusion, indicates that signalling pathway associated with nitric oxide (NO) and cGMP regulates the tension of the vascular smooth muscle cells. PMID- 27563665 TI - Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico. AB - The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans. PMID- 27563667 TI - Stress Signaling Responses in Plants. PMID- 27563666 TI - Development of Primer Pairs from Molecular Typing of Rabies Virus Variants Present in Mexico. AB - Nucleoprotein (N) gene from rabies virus (RABV) is a useful sequence target for variant studies. Several specific RABV variants have been characterized in different mammalian hosts such as skunk, dog, and bats by using anti-nucleocapsid monoclonal antibodies (MAbs) via indirect fluorescent antibody (IFA) test, a technique not available in many laboratories in Mexico. In the present study, a total of 158 sequences of N gene from RABV were used to design eight pairs of primers (four external and four internal primers), for typing four different RABV variants (dog, skunk, vampire bat, and nonhematophagous bat) which are most common in Mexico. The results indicate that the primer and the typing variant from the brain samples, submitted to nested and/or real-time PCR, are in agreement in all four singleplex reactions, and the designed primer pairs are an alternative for use in specific variant RABV typing. PMID- 27563668 TI - A Retrospective Observational Study to Assess Prescription Pattern in Patients with Type B Aortic Dissection and Treatment Outcome. AB - Aortic dissection is a life-threatening condition. However, the use of medication to treat it remains unclear in our population, particularly in patients with a type B aortic dissection (TBAD) who do not receive surgery. This retrospective cohort study evaluated antihypertensive prescription patterns and outcomes in patients with nonsurgical TBAD. We reviewed the hospital records of patients with TBAD at a medical center in Taiwan from January 2008 to June 2013 to assess the baseline information, prescribing pattern, event rate, and clinical effectiveness of different antihypertensive treatment strategies. A Cox proportional hazards model was used to estimate outcomes in different antihypertensive strategies. The primary endpoints were all-cause mortality and hospital admission for an aortic dissection. We included 106 patients with a mean follow-up period of 2.75 years. The most common comorbidity was hypertension followed by dyslipidemia and diabetes mellitus. Study endpoints mostly occurred within 6 months after the index date. Over 80% of patients received dual or triple antihypertensive strategies. Patients treated with different treatment strategies did not have a significantly increased risk of a primary outcome compared with those treated with a monotherapy. We found no significant difference in the primary outcome following the use of different antihypertensive medication regimes. PMID- 27563669 TI - Relationship between Antibody Levels, IgG Binding to Plasmodium falciparum Infected Erythrocytes, and Disease Outcome in Hospitalized Urban Malaria Patients from Dakar, Senegal. AB - Background. Management of clinical malaria requires the development of reliable diagnostic methods and efficient biomarkers for follow-up of patients. Protection is partly based on IgG responses to parasite antigens exposed at the surface of infected erythrocytes (iRBCs). These IgG responses appeared low during clinical infection, particularly in severe disease. Methods. We analyzed the IgG binding capacity to the surface of live erythrocytes infected by knob positive FCR3 strain. Sera from 69 cerebral malaria (CM) and 72 mild malaria (MM) cases were analyzed by ELISA for IgG responses to five antigens from iRBC and by flow cytometry for IgG binding as expressed in labeling index ratio (LIR). The relationship between IgG levels, LIR, parasitemia, age, and the clinical outcomes was evaluated. Results. We found a significant decrease of LIR in adult CM fatal cases compared to surviving patients (p = 0.019). In MM, LIRs were correlated to IgG anti-iRBC and anti-PfEMP3/5 levels. In CM, no correlation was found between LIR, IgG levels, and parasitemia. Conclusion. The IgG binding assay was able to discriminate outcome of cerebral malaria cases and it deserves further development as a potential functional-associated assay for symptomatic malaria analysis. PMID- 27563670 TI - Effects of 8-Week Hatha Yoga Training on Metabolic and Inflammatory Markers in Healthy, Female Chinese Subjects: A Randomized Clinical Trial. AB - We aimed to determine the effects of an 8 wk Hatha yoga training on blood glucose, insulin, lipid profiles, endothelial microparticles (EMPs), and inflammatory status in healthy, lean, and female Chinese subjects. A total of 30 healthy, female Chinese subjects were recruited and randomized into control or yoga practice group. The yoga practice included 8 wks of yoga practice (2 times/wk) for a total of 16 times. Fasting blood samples were collected before and after yoga training. Plasma was isolated for the measurement of lipid profiles, glucose, insulin, EMPs, and inflammatory cytokines. Whole blood was cultured ex vivo and stimulated with lipopolysaccharide (LPS) and Pam3Cys-SK4. Peripheral blood mononuclear cells (PBMCs) were isolated for the measurement of TLR2 and TLR4 protein expression. Yoga practice significantly reduced plasma cholesterol, LDL-cholesterol, insulin levels, and CD31+/CD42b- EMPs. Cultured whole blood from the yoga group has reduced proinflammatory cytokines secretion both at unstimulated condition and when stimulated with Pam3Cys-SK4; this might be associated with reduced TLR2 protein expression in PBMCs after yoga training. Hatha yoga practice in healthy Chinese female subjects could improve hallmarks related to MetS; thus it can be considered as an ancillary intervention in the primary MetS prevention for the healthy population. This trial is registered with ChiCTR-IOR-14005747. PMID- 27563671 TI - Efficient Catalyst One-Pot Synthesis of 7-(Aryl)-10,10-dimethyl-10,11 dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione Derivatives Complemented by Antibacterial Activity. AB - The problem of bacteria resistance to many known agents has inspired scientists and researchers to discover novel efficient antibacterial drugs. Three rapid, clean, and highly efficient methods were developed for one-pot synthesis of 7 (aryl)-10,10-dimethyl-10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione derivatives. Three components are condensed in the synthesis, 4-hydroxycoumarin, 5,5-dimethyl-1,3-cyclohexanedione, and aromatic aldehydes, using tetrabutylammonium bromide (TBAB), diammonium hydrogen phosphate (DAHP), or ferric chloride (FeCl3), respectively. Each method has different reaction mechanisms according to the catalyst. The present methods have advantages, including one-pot synthesis, excellent yields, short reaction times, and easy isolation of product. All catalysts utilized in our study could be reused several times without losing their catalytic efficiency. All synthesized compounds were fully characterized and evaluated for their antibacterial activity. PMID- 27563672 TI - Association between TLR4 and PTEN Involved in LPS-TLR4 Signaling Response. AB - In this study, we explored the potential mechanisms of how PTEN regulating LPS induced TLR4 signaling pathway. The initial findings from ELISA demonstrate that PTEN influences TNF-alpha secretion by its lipid phosphatase activity. Subsequently, western blot, immunoprecipitation assay, and immunofluorescence were performed to explore the activation process of PTEN by stimulation with LPS. As early as 20 minutes after LPS stimulation, reduced phosphorylation of PTEN was found obviously. Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. Moreover, the weak physical association between PTEN and TLR4 in resting RAW264.7 cells increased gradually after the stimulation of LPS. Furthermore, our study showed PTEN decreased LPS-induced Akt activity and upregulated NF-kappaB-dependent gene transcription, identifying indirectly that the PTEN could regulate the activation of NF-kappaB by its downstream Akt kinase. In summary, our study illustrates the potential signal transduction process of PTEN while stimulated by LPS: by increasing the association of TLR4, PTEN recruits to its phosphoinositide substrate PI(3,4,5)P3 located on the cell membrane and exerts its dephosphorylated function and subsequently depresses the activity of downstream molecule Akt and results in activation of NF-kappaB, followed by the secretion of inflammatory mediators TNF-alpha. PMID- 27563674 TI - Detection of Extended Spectrum Beta-Lactamases Resistance Genes among Bacteria Isolated from Selected Drinking Water Distribution Channels in Southwestern Nigeria. AB - Extended Spectrum Beta-Lactamases (ESBL) provide high level resistance to beta lactam antibiotics among bacteria. In this study, previously described multidrug resistant bacteria from raw, treated, and municipal taps of DWDS from selected dams in southwestern Nigeria were assessed for the presence of ESBL resistance genes which include bla TEM, bla SHV, and bla CTX by PCR amplification. A total of 164 bacteria spread across treated (33), raw (66), and municipal taps (68), belonging to alpha-Proteobacteria, beta-Proteobacteria, gamma-Proteobacteria, Flavobacteriia, Bacilli, and Actinobacteria group, were selected for this study. Among these bacteria, the most commonly observed resistance was for ampicillin and amoxicillin/clavulanic acid (61 isolates). Sixty-one isolates carried at least one of the targeted ESBL genes with bla TEM being the most abundant (50/61) and bla CTX being detected least (3/61). Klebsiella was the most frequently identified genus (18.03%) to harbour ESBL gene followed by Proteus (14.75%). Moreover, combinations of two ESBL genes, bla SHV + bla TEM or bla CTX + bla TEM, were observed in 11 and 1 isolate, respectively. In conclusion, classic bla TEM ESBL gene was present in multiple bacterial strains that were isolated from DWDS sources in Nigeria. These environments may serve as foci exchange of genetic traits in a diversity of Gram-negative bacteria. PMID- 27563673 TI - Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options. AB - Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy. PMID- 27563675 TI - ChSte7 Is Required for Vegetative Growth and Various Plant Infection Processes in Colletotrichum higginsianum. AB - Colletotrichum higginsianum is an important hemibiotrophic phytopathogen that causes crucifer anthracnose in various regions of the world. In many plant pathogenic fungi, the Ste11-Ste7-Fus3/Kss1 kinase pathway is essential to pathogenicity and various plant infection processes. To date, the role of ChSte7 in C. higginsianum encoding a MEK orthologue of Ste7 in Saccharomyces cerevisiae has not been elucidated. In this report, we investigated the function of ChSte7 in the pathogen. The ChSte7 is predicted to encode a 522-amino-acid protein with a S_TKc conserved domain that shares 44% identity with Ste7 in S. cerevisiae. ChSte7 disruption mutants showed white colonies with irregularly shaped edges and extremely decreased growth rates and biomass productions. The ChSte7 disruption mutants did not form appressoria and showed defects in pathogenicity on leaves of Arabidopsis thaliana. When inoculated onto wounded leaf tissues, the ChSte7 disruption mutants grew only on the surface of host tissues but failed to cause lesions beyond the wound site. In contrast, both the wild-type and complementation strains showed normal morphology, produced appressoria, and caused necrosis on leaves of Arabidopsis. Analysis with qRT-PCR suggested that ChSte7 was highly expressed during the late stages of infection. Taken together, our results demonstrate that ChSte7 is involved in regulation of vegetative growth, appressorial formation of C. higginsianum, and postinvasive growth in host tissues. PMID- 27563676 TI - The Midterm Surgical Outcome of Modified Expansive Open-Door Laminoplasty. AB - Laminoplasty is a standard technique for treating patients with multilevel cervical spondylotic myelopathy. Modified expansive open-door laminoplasty (MEOLP) preserves the unilateral paraspinal musculature and nuchal ligament and prevents facet joint violation. The purpose of this study was to elucidate the midterm surgical outcomes of this less invasive technique. We retrospectively recruited 65 consecutive patients who underwent MEOLP at our institution in 2011 with at least 4 years of follow-up. Clinical conditions were evaluated by examining neck disability index, Japanese Orthopaedic Association (JOA), Nurick scale, and axial neck pain visual analog scale scores. Sagittal alignment of the cervical spine was assessed using serial lateral static and dynamic radiographs. Clinical and radiographic outcomes revealed significant recovery at the first postoperative year and still exhibited gradual improvement 1-4 years after surgery. The mean JOA recovery rate was 82.3% and 85% range of motion was observed at the final follow-up. None of the patients experienced aggravated or severe neck pain 1 year after surgery or showed complications of temporary C5 nerve palsy and lamina reclosure by the final follow-up. As a less invasive method for reducing surgical dissection by using various modifications, MEOLP yielded satisfactory midterm outcomes. PMID- 27563677 TI - Outcomes of a Management Strategy in Eyes with Corneal Irregularity and Cataract. AB - Purpose. To evaluate the outcomes of a management strategy in patients with irregular corneas and cataract. Methods. Six eyes of four patients presented for cataract surgery with irregular corneas following corneal refractive surgery. Topoguided ablation regularised the cornea, followed by phacoemulsification and intraocular lens implantation. Zonal keratometric coefficient of variation (ZKCV) measured structural changes and visual quality metrics measured functional improvement. Results. The mean duration after corneal refractive surgery was 7.83 +/- 2.40 years. The logmar uncorrected distance visual acuity (0.67 +/- 0.25) and the corrected distance visual acuity (0.38 +/- 0.20) improved to 0.34 +/- 0.14 and 0.18 +/- 0.10, respectively. The changes in the standard deviations of the zonal keratometry values and the ZKCV were statistically significant in the 2, 3, and 4 mm zones. The changes in the Strehl ratio (ANOVA p = 0.043) were also statistically significant. Conclusions. Corneal regularisation followed by phacoemulsification resulted in lower residual refractive error with improved visual quality metrics. This strategy is a viable option in patients with symptomatic cataracts and irregular corneas. PMID- 27563678 TI - Structural Changes of Lignin after Liquid Hot Water Pretreatment and Its Effect on the Enzymatic Hydrolysis. AB - During liquid hot water (LHW) pretreatment, lignin is mostly retained in the pretreated biomass, and the changes in the chemical and structural characteristics of lignin should probably refer to re-/depolymerization, solubilization, or glass transition. The residual lignin could influence the effective enzymatic hydrolysis of cellulose. The pure lignin was used to evaluate the effect of LHW process on its structural and chemical features. The surface morphology of LHW-treated lignin observed with the scanning electron microscopy (SEM) was more porous and irregular than that of untreated lignin. Compared to the untreated lignin, the surface area, total pore volume, and average pore size of LHW-treated lignin tested with the Brunner-Emmet-Teller (BET) measurement were increased. FTIR analysis showed that the chemical structure of lignin was broken down in the LHW process. Additionally, the impact of untreated and treated lignin on the enzymatic hydrolysis of cellulose was also explored. The LHW-treated lignin had little impact on the cellulase adsorption and enzyme activities and somehow could improve the enzymatic hydrolysis of cellulose. PMID- 27563679 TI - The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus. AB - This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients. PMID- 27563680 TI - Social Support Groups in the Maintenance of Glycemic Control after Community Based Intervention. AB - Native Hawaiians and other Pacific Islanders (NH/PI; e.g., Samoan and Chuukese) have higher type 2 diabetes prevalence compared to other groups in Hawai'i. Partners in Care (PIC), a culturally tailored, community-based, diabetes self management education intervention (DSME), is effective at improving participants' glycemic control and self-care behaviors. Maintenance of improvements is challenging. Diabetes-related social support groups (SSG) are a promising maintenance component for DSME. This study examined the effects of a diabetes specific SSG component relative to a control group, after the receipt of the 3 month PIC intervention, which was delivered to 47 adult NH/PI with type 2 diabetes. Participants were then randomized to either a 3-month, 6-session SSG or a control group. Hemoglobin A1c (HbA1c), blood pressure, triglycerides, cholesterol, and diabetes self-management knowledge and behaviors were assessed at baseline, 3 months, and 6 months. Results indicated significant improvements in HbA1c, diabetes-related self-management knowledge, and behaviors from baseline to 3-month assessment. However, no differences between the SSG and control group from 3-month to 6-month assessment suggest that all participants were able to maintain initial improvements. The SSG group had a significant decrease in systolic blood pressure from 3-month to 6-month assessment while the control group did not. Study limitations and future directions are discussed. PMID- 27563681 TI - Predictors of Diabetes Self-Management among Type 2 Diabetes Patients. AB - Diabetes mellitus is a public health concern in Malaysia. Treatment of diabetes is costly and can lead to complications if disease is poorly controlled. Diabetes self-management (DSM) is found to be essential for optimal glycemic control. This cross-sectional study was conducted among samples from four randomly selected diabetes clinics in Sarawak, Malaysia. The aim was to determine the predictors for DSM. Face-to-face interview using questionnaire was used to collect data. Four hundred respondents with type 2 diabetes mellitus (T2DM) were recruited. Majority of the respondents were Sarawak Bumiputra (Iban and Bidayuh, 48.6%) and female (68.6%). The mean age was 58.77 years (SD = 11.46) and approximately half of the respondents (50.6%) had T2DM for six years (SD = 4.46). The mean fasting blood glucose (FBG) was 8.06 mmol/L (SD = 2.94), with majority (76.1%) having the level higher than 6.1 mmol/L. Multiple logistic regression tests showed significant linear relationship between DSM and belief in treatment effectiveness (p = 0.001), family support (p = 0.007), and self-efficacy (p = 0.027). Health care personnel must convince patients with T2DM of the effectiveness of the treatment, empower and enhance their self-efficacy, and enlist the family support so as to ensure patients sustain their DSM efforts. PMID- 27563683 TI - Collecting, Integrating, and Disseminating Patient-Reported Outcomes for Research in a Learning Healthcare System. AB - INTRODUCTION: Advances in health policy, research, and information technology have converged to increase the electronic collection and use of patient-reported outcomes (PROs). Therefore, it is important to share lessons learned in implementing PROs in research information systems. CASE DESCRIPTION: The purpose of this case study is to describe a novel information system for electronic PROs and lessons learned in implementing that system to support research in an academic health center. The system incorporates freely available and commercial software and involves clinical and research workflows that support the collection, transformation, and research use of PRO data. The software and processes that comprise the system serve three main functions, (i) collecting electronic PROs in clinical care, (ii) integrating PRO data with non-patient generated clinical data, and (iii) disseminating data to researchers through the institution's research informatics infrastructure, including the i2b2 (Informatics for Integrating Biology and the Bedside) system. STRATEGIES: Our successful design and implementation was driven by three overarching strategies. First, we selected and implemented multiple interfaced technologies to support PRO collection, management, and research use. Second, we aimed to use standardized approaches to measuring PROs, sending PROs between systems, and disseminating PROs. Finally, we focused on using technologies and processes that aligned with existing clinical research information management strategies within our organization. CONCLUSION: These experiences and lessons may help future implementers and researchers enhance the scale and sustainable use of systems for research use of PROs. PMID- 27563684 TI - Applying Sequential Analytic Methods to Self-Reported Information to Anticipate Care Needs. AB - PURPOSE: Identifying care needs for newly enrolled or newly insured individuals is important under the Affordable Care Act. Systematically collected patient reported information can potentially identify subgroups with specific care needs prior to service use. METHODS: We conducted a retrospective cohort investigation of 6,047 individuals who completed a 10-question needs assessment upon initial enrollment in Kaiser Permanente Colorado (KPCO), a not-for-profit integrated delivery system, through the Colorado State Individual Exchange. We used responses from the Brief Health Questionnaire (BHQ), to develop a predictive model for cost for receiving care in the top 25 percent, then applied cluster analytic techniques to identify different high-cost subpopulations. Per-member, per-month cost was measured from 6 to 12 months following BHQ response. RESULTS: BHQ responses significantly predictive of high-cost care included self-reported health status, functional limitations, medication use, presence of 0-4 chronic conditions, self-reported emergency department (ED) use during the prior year, and lack of prior insurance. Age, gender, and deductible-based insurance product were also predictive. The largest possible range of predicted probabilities of being in the top 25 percent of cost was 3.5 percent to 96.4 percent. Within the top cost quartile, examples of potentially actionable clusters of patients included those with high morbidity, prior utilization, depression risk and financial constraints; those with high morbidity, previously uninsured individuals with few financial constraints; and relatively healthy, previously insured individuals with medication needs. CONCLUSIONS: Applying sequential predictive modeling and cluster analytic techniques to patient-reported information can identify subgroups of individuals within heterogeneous populations who may benefit from specific interventions to optimize initial care delivery. PMID- 27563682 TI - Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis. AB - Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic "hygiene hypothesis," has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis. PMID- 27563685 TI - What Causes Care Coordination Problems? A Case for Microanalysis. AB - INTRODUCTION: Care coordination (CC) is an important fulcrum for pursuing a range of health care goals. Current research and policy analyses have focused on aggregated data rather than on understanding what happens within individual cases. At the case level, CC emerges as a complex network of communications among providers over time, crossing and recrossing many organizational boundaries. Micro-level analysis is needed to understand where and how CC fails, as well as to identify best practices and root causes of problems. COORDINATION PROCESS DIAGRAMMING: Coordination Process Diagramming (CPD) is a new framework for representing and analyzing CC arcs at the micro level, separating an arc into its participants and roles, communication structure, organizational structures, and transitions of care, all on a common time line. CONCLUSION: Comparative CPD analysis across a sample of CC arcs identifies common CC problems and potential root causes, showing the potential value of the framework. The analyses also suggest intervention strategies that could be applied to attack the root causes of CC problems, including organizational changes, education and training, and additional health information technology development. PMID- 27563686 TI - A Framework to Support the Sharing and Reuse of Computable Phenotype Definitions Across Health Care Delivery and Clinical Research Applications. AB - INTRODUCTION: The ability to reproducibly identify clinically equivalent patient populations is critical to the vision of learning health care systems that implement and evaluate evidence-based treatments. The use of common or semantically equivalent phenotype definitions across research and health care use cases will support this aim. Currently, there is no single consolidated repository for computable phenotype definitions, making it difficult to find all definitions that already exist, and also hindering the sharing of definitions between user groups. METHOD: Drawing from our experience in an academic medical center that supports a number of multisite research projects and quality improvement studies, we articulate a framework that will support the sharing of phenotype definitions across research and health care use cases, and highlight gaps and areas that need attention and collaborative solutions. FRAMEWORK: An infrastructure for re-using computable phenotype definitions and sharing experience across health care delivery and clinical research applications includes: access to a collection of existing phenotype definitions, information to evaluate their appropriateness for particular applications, a knowledge base of implementation guidance, supporting tools that are user-friendly and intuitive, and a willingness to use them. NEXT STEPS: We encourage prospective researchers and health administrators to re-use existing EHR-based condition definitions where appropriate and share their results with others to support a national culture of learning health care. There are a number of federally funded resources to support these activities, and research sponsors should encourage their use. PMID- 27563687 TI - Using anti-biofilm peptides to treat antibiotic-resistant bacterial infections. AB - Host defense (antimicrobial) peptides (HDPs) are produced by virtually all organisms and have an important role in protection against microbial infections. Some naturally occurring peptides such as the human cathelicidin LL-37 and the bovine peptide indolicidin have been shown to inhibit bacterial biofilm development. Rearrangement and substantial modification of the amino acid sequence of these and other HDPs has led to the identification of small synthetic peptides with increased, broad-spectrum anti-biofilm activity that is independent of activity vs. planktonic cells. Some of these peptides have also been shown to act in synergy with antibiotics commonly used in the clinic to prevent biofilm formation and eradicate pre-existing biofilms. Recently, the mechanism of action of one of these peptides (i.e., 1018) was shown to involve binding to and causing degradation of the second messenger stress response nucleotide ppGpp, which plays an important role in biofilm formation and maintenance. Here, we review recent progress in the field of anti-biofilm peptides and propose future directions to further develop these therapeutic agents. PMID- 27563688 TI - Harmonics Generation by Surface Plasmon Polaritons on Single Nanowires. AB - We present experimental observations of visible wavelength second- and third harmonic generation on single plasmonic nanowires of variable widths. We identify that near-infrared surface plasmon polaritons, which are guided along the nanowire, act as the source of the harmonics generation. We discuss the underlying mechanism of this nonlinear process, using a combination of spatially resolved measurements and numerical simulations to show that the visible harmonics are generated via a combination of both local and propagating plasmonic modes. Our results provide the first demonstration of nanoscale nonlinear optics with guided, propagating plasmonic modes on a lithographically defined chip, opening up new routes toward integrated optical circuits for information processing. PMID- 27563689 TI - Dimethoate Induced Behavioural Changes in Juveniles of Cyprinus carpio var. communis under Temperate Conditions of Kashmir, India. AB - The present study was designed to investigate acute toxicity of dimethoate on juvenile Cyprinus carpio var. communis. Fishes weighing 10 +/- 2 gms were selected and mortality data was statistically evaluated by Finney's Probit Method. The 96-hour LC50 value for Cyprinus carpio was found as 1.1 ppm in static bioassay system. Mean values of physicochemical parameters of aquarium waters determined during bioassay depicted slight variation indicating that the mortality in aquarium fishes occurred due to pesticide exposure and not suffocation. Lab. temperature ranged from 12 to 13 degrees C; water temperature ranged from 11 to 12 degrees C; dissolved oxygen ranged from 3.90 to 4.56 mg/L; pH ranged from 6.90 to 7.05; total dissolved solids ranged from 2.66 to 3.0 * 10(3) mg/L, while CO2 remained at a constant value of 2.0 mg/L. The fishes elicited various behavioural responses such as uncoordinated movements, convulsions, excessive mucus secretion, and imbalanced swimming which ended in a collapse to the bottom of the aquarium. Prior to death, the clinical signs like scale erosion, pale body colour, and hemorrhagic patches over the body were noticed which became more vivid up to the termination of experiments. Results of the study indicate potential toxicity of dimethoate in fingerlings of common carp for which the natural waterbodies must be continuously monitored to reduce its impact across food chains. PMID- 27563690 TI - Using panel data to examine pregnancy attitudes over time. AB - There is a lack of research examining changes in women's fertility attitudes over relatively short periods of time. The aim of this study was to determine whether and how women's attempts to get pregnant and their desire to avoid pregnancy changed over six months' time as well as which characteristics and circumstances were associated with these changes. Using multinomial regression, we analyzed two panels of data from a sample of approximately 3,000 U.S. adult women gathered within six months apart. Only 4% of the women were trying to get pregnant at both time points, but six percent went from trying to not or vice versa. Two-thirds reported a strong desire to avoid pregnancy at both points, but 9% transitioned from strong to not strong and an additional 7% transitioned from not strong to strong. Women who transitioned to a more serious romantic relationship were at increased risk of transitioning to trying to become pregnant and, not surprisingly, to a weaker pregnancy avoidance. Some of the variables we tested, including changes in employment status and race/ethnicity, were associated with one outcome but not the other. The results highlight the importance of taking a holistic perspective of women's lives when studying pregnancy intentions and in reproductive health care services such as contraceptive counseling. Context matters and it may change rapidly. PMID- 27563691 TI - Effects of corexit oil dispersants and the WAF of dispersed oil on DNA damage and repair in cultured human bronchial airway cells, BEAS-2B. AB - Large quantities of dispersants were used as a method to disperse the roughly 210 million gallons of spilled crude oil that consumed the Gulf of Mexico. Little is known if the oil-dispersant and oil-dispersant mixtures on human airway BEAS-2B epithelial cells. Here we present the cytotoxic and genotoxic in vitro effects on the human lung cells BEAS-2B following exposure to and oil-dispersant mixtures on human airway BEAS-2B epithelial cells. Here we present the cytotoxic and genotoxic in vitro effects on the human lung cells BEAS-2B following exposure to Corexit dispersants EC9500 and EC9527, Water Accommodated Fraction (WAF) -crude, WAF-9500 + Oil, and WAF-9527 + Oil. Cellular cytotoxicity to WAF-dispersed oil samples was observed at concentrations greater than 1000 ppm with over 70% of observed cellular death. At low concentration exposures (100 and 300 ppm) DNA damage was evidenced by the detection of single strand breaks (SSBs) and double strand breaks (DSBs) as measured by alkaline and neutral comet assay analyses. Immunoblot analyses of the phosphorylated histone H2A.X (gamma-H2A.X) and tumor suppressor p53 protein confirmed activation of the DNA damage response due to the exposure-induced DNA breaks. Although, many xenobiotics interfere with DNA repair pathways, in vitro evaluation of the nucleotide excision repair (NER) and DSB repair pathways appear to be unaffected by the oil-dispersant mixtures tested. Overall, this study supports that oil-dispersant mixtures induce genotoxic effects in culture. PMID- 27563692 TI - Engaging African Americans in developing an intervention to reduce breast cancer recurrence: A brief report. AB - BACKGROUND: To develop a culturally appropriate lifestyle intervention, involvement of its intended users is needed. METHODS: Members of an African American (AA) breast cancer support group participated in two 4-hour guided discussions, which were audiotaped, transcribed, and analyzed to guide the content. RESULTS: The support group collaborated with researchers to develop 24 experiential nutrition education sessions using a social cognitive framework and incorporating self-regulation skills (goal-setting, self-monitoring, problem solving, stimulus control) and social support to enhance self-efficacy for changes in dietary intake. CONCLUSIONS: Community engagement fostered autonomy, built collaboration, and enhanced the capacity of AA breast cancer survivors to participate in developing a lifestyle intervention. PMID- 27563693 TI - Macronutrient Composition and Management of Non-Insulin-Dependent Diabetes Mellitus (NIDDM): A New Paradigm for Individualized Nutritional Therapy in Diabetes Patients. AB - Medical nutrition therapy constitutes an important lifestyle intervention in diabetes management. Several nutrition patterns have been effective in improving diabetes control, but there has been a debate about the optimal macronutrient composition in diabetes meal planning. For many years, the recommended diets for persons with and without diabetes were similar, i.e. heart-healthy and low in fat. For almost three decades, carbohydrates have been lauded, lipids demonized, and proteins considered of little importance. However, in the past few years, this concept has been questioned and reassessed. Modern nutritional recommendations for people with diabetes are headed towards individualization, but lack specific guidelines. Nutritional algorithms may help nutritionists in diabetes meal planning. This review aims to discuss: 1) the effects of the three major macronutrients (carbohydrates, proteins, and lipids) on glucose levels, 2) current recommendations for macronutrient intake for people with diabetes, and 3) specific parameters that need to be taken into consideration when determining the macronutrient composition for a person with diabetes, for example body mass index, degree of insulin resistance, HbA1c value, and lipid profile (especially triglycerides and HDL cholesterol). These aspects are analyzed in the context of the results of recent studies, especially randomized controlled trials (RCTs). Finally, we introduce an individualized nutritional concept that proposes carbohydrate over lipid restriction, substitution of SFAs with MUFAs and PUFAs, and adequate intake of dietary fiber, which are key factors in optimizing diabetes management. PMID- 27563694 TI - Understanding Genetic Heterogeneity in Type 2 Diabetes by Delineating Physiological Phenotypes: SIRT1 and its Gene Network in Impaired Insulin Secretion. AB - Type 2 diabetes (T2D) is a chronic metabolic disease which shows an exponential increase in all parts of the world. However, the disease is controllable by early detection and modified lifestyle. A series of factors have been associated with the pathogenesis of diabetes, and genes are considered to play a critical role. The individual risk of developing T2D is determined by an altered genetic background of the en-zymes involved in several metabolism-related biological mechanisms, including glucose homeostasis, insulin metab-olism, the glucose and ion transporters involved in glucose uptake, transcription factors, signaling intermediates of insulin signaling pathways, insulin production and secretion, pancreatic tissue development, and apoptosis. However, many candidate genes have shown heterogeneity of associations with the disease in different populations. A possible approach to resolving this complexity and under-standing genetic heterogeneity is to delineate the physiological phenotypes one by one as studying them in combination may cause discrepancies in association studies. A systems biology approach involving regulatory proteins, transcription factors, and microRNAs is one way to understand and identify key factors in complex diseases such as T2D. Our earlier studies have screened more than 100 single nucleotide polymorphisms (SNPs) belonging to more than 60 globally known T2D candidate genes in the Indian population. We observed that genes invariably involved in the activity of pancreatic beta-cells provide susceptibility to type 2 diabetes (T2D). Encouraged by these results, we attempted to delineate in this review one of the commonest physiological phenotypes in T2D, namely impaired insulin secretion, as the cause of hyperglycemia. This review is also intended to explain the genetic basis of the pathophysiology of insulin secretion in the context of variations in the SIRT1 gene, a major switch that modulates insulin secretion, and a set of other genes such as HHEX, PGC-alpha, TCF7L2, UCP2, and ND3 which were found to be in association with T2D. The review aims to look at the genotypic and transcriptional regulatory relationships with the disease phenotype. PMID- 27563695 TI - Chronic Exposure to Proline Causes Aminoacidotoxicity and Impaired Beta-Cell Function: Studies In Vitro. AB - BACKGROUND: Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary beta-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed beta-cell function, gene expressions, and cell death after long-term exposure of pancreatic beta-cells to excess proline in vitro. METHODS: Isolated mouse islets and INS-1E cells were incubated with and without excess proline. After 72 h, we examined: (1) beta-cell function, including basal insulin secretion (BIS) and glucose stimulated insulin secretion (GSIS), (2) transcription factors related to insulin gene expression and enzymes involved in the tricarboxylic acid cycle and cholesterol biogenesis, (3) cellular triglycerides (TG) and cholesterol content, (4) the death of INS-1E cells and 3H thymidine incorporation, and (5) protein expression of INS-1E cells in response to proline by proteomics. RESULTS: We found that high doses of proline increased BIS and decreased GSIS in both isolated mouse islets and INS-1E cells. MafA, insulin 1, and the cytochrome c oxidase subunit VIa polypeptide 2 mRNA expressions were all downregulated, indicating that proline impaired insulin gene transcription and mitochondrial oxidative phosphorylation. In contrast, mevalonate decarboxylase gene expression was upregulated, and simultaneously, cholesterol content in INS-1E cells was enhanced. Protein profiling of INS-1E cells revealed that cytosolic non-specific dipeptidase and alpha enolase were differentially expressed. CONCLUSIONS: Our results indicate that proline-induced insulin transcription and mitochondrial oxidative phosphorylation impairment may contribute to the beta-cell dysfunction observed in type 2 diabetes. Caution should be applied in interpreting the pathophysiological role of proline since very high proline concentrations were used in the experiments. PMID- 27563696 TI - Esophageal and Gastric Dysmotilities are Associated with Altered Glucose Homeostasis and Plasma Levels of Incretins and Leptin. AB - BACKGROUND: Gastrointestinal complications in diabetes may affect glucose and endocrine homeostasis. Glucose-dependent insulinotropic peptide (GIP), glucagon like peptide-1 (GLP-1), and leptin regulate glucose homeostasis, food intake, and gastric emptying. AIM: The aim was to investigate associations between diabetes complications and glucose homeostasis and plasma levels of GIP, GLP-1, and leptin. METHODS: Sixteen diabetes patients (seven men) were examined with gastric emptying scintigraphy and 72-h continuous subcutaneous glucose monitoring, 14 with the deep-breathing test, and 12 with esophageal manometry. A fiber-rich breakfast was given during the second day of glucose registration. Blood samples were taken 10 min and right before a fat-rich breakfast, as well as 10, 20, 30, 45, 60, 90, 120, 150, and 180 min afterwards. 20 healthy volunteers acted as controls. Plasma was analyzed regarding GIP, GLP-1, and leptin by Luminex. RESULTS: Gastroparesis lowered maximal concentration (c-max) (p = 0.003) and total area under the curve (tAUC) (p = 0.019) of glucose levels as well as d-min (p = 0.043) of leptin levels. It tended to lower baseline (p = 0.073), c-max (p = 0.066), change from baseline (d-max) (p = 0.073), and tAUC (p = 0.093) of GLP-1 concentrations. Esophageal dysmotility tended to lower tAUC of glucose levels (p = 0.063), and c-min (p = 0.065) and tAUC (p = 0.063) of leptin levels. Diabetes patients had a higher baseline concentration of glucose (p = 0.013), GIP (p = 0.023), and leptin (p = 0.019) compared with healthy subjects. CONCLUSIONS: Gastric and esophageal dysmotility are associated with both lesser increases in postprandial glucose elevations and decreased postprandial changes in GLP-1 and leptin. PMID- 27563697 TI - Functional recovery after stroke in Benin: A six-month follow-up study. AB - OBJECTIVE: Stroke is a major public health problem in developing countries. However, few studies have quantified the functional recovery of stroke patients in sub-Saharan Africa. This study examined the functional recovery of stroke patients in the Republic of Benin. METHODS: A total of 68 patients with acute stroke were recruited from hospitals and health centres in Benin. Patients were evaluated at enrolment and 1, 3 and 6 months post-stroke. The ACTIVLIM-Stroke scale, Barthel Index, and modified Rankin Scale were used to assess activity limitations, functional autonomy, and overall level of disability, respectively. RESULTS: Over the 6-month follow-up period, 18 patients died and 9 dropped out. Overall, the 3 measures highlighted progressive and significant functional recovery during the first 6 months. At enrolment, the mean score on ACTIVLIM Stroke was 16% (standard deviation (SD) 9), indicating that patients were almost totally dependent and unable to perform most activities of daily living. At 6 months, the mean score for activity limitation reached 67% (SD 15) and most patients were able to perform some basic tasks easily. Patients had difficulty with tasks requiring walking and remained unable to perform certain activities requiring manual dexterity. CONCLUSION: The study sample showed significant functional recovery (~50%) during the first 6 months post-stroke. We recommend the integration of group-based brisk walking into a cost-effective rehabilitation programme as a suitable way to increase functional recovery of chronic stroke patients in sub-Saharan Africa after hospital discharge. PMID- 27563698 TI - Sideways walk test: Reliability and association with lower limb motor function after stroke. AB - OBJECTIVES: To investigate (i) the intra-rater, inter-rater and test-retest reliability of sideways walk test times and counts in individuals with stroke; (ii) their correlations with stroke-specific measures of impairment; (iii) the cut-off sideways walk test times and counts between stroke survivors and healthy controls; and (iv) the minimum detectable changes in the sideways walk test times and counts. DESIGN: Cross-sectional study. SETTING: University-based rehabilitation centre. SUBJECTS: Twenty-nine older adults with stroke and 32 healthy controls. METHODS: The sideways walk test was conducted together with Fugl-Meyer motor assessments of the lower extremities, lower limb muscle strength tests, the Five-Times-Sit-To-Stand test, Berg Balance Scale, Timed Up-and-Go test, and Activity-based Confidence and Community Integration Measure questionnaires. RESULTS: The sideways walk test times and counts demonstrated good to excellent intra-rater, inter-rater, and test-retest reliabilities. The sideways walk test times and counts were significantly correlated with motor control and ankle dorsiflexor and plantarflexor strength of the affected leg, balance performance and functional mobility. The cut-off sideways walk test time and count that best discriminated between individuals with stroke and controls were 10.74 s and 8.83 steps, respectively. The minimal detectable change in the sideways walk test time in that situation was 1.85 s, and the count minimum detectable change was 1.12 steps. CONCLUSION: The sideways walk test is a reliable and easy-to-administer clinical test for assessing sideways walking ability of individuals with chronic stroke. PMID- 27563699 TI - Early access to vocational rehabilitation for inpatients with spinal cord injury: A qualitative study of staff perceptions. AB - INTRODUCTION: Early intervention is among the factors frequently associated with more positive vocational rehabilitation outcomes; however, vocational rehabilitation is not generally a core component of inpatient rehabilitation following spinal cord injury. OBJECTIVE: This qualitative study explored the opinions and perceptions of health professionals regarding InVoc, an early vocational rehabilitation intervention provided to spinal cord injury unit inpatients. The aim of this evaluation was to determine the critical elements of the InVoc programme, and whether it was perceived as successfully implemented in the hospital setting. METHODS: Twenty-five medical and allied health staff working in the 3 Spinal Cord Injury Units in New South Wales, Australia, participated in the qualitative study. Three staff focus-group discussions were conducted and data analysed thematically. RESULTS: Four themes emerged: timeliness of the intervention, support and advocacy, value of early intervention, and conflicting messages to patients. Three critical programme elements were identified: flexibility, coordinators working on the ward, and good communication between all staff. CONCLUSION: Early vocational rehabilitation was perceived as appropriate and successfully implemented in the spinal injury unit in-patient setting, addressing an existing gap in patient care. The InVoc programme was seen to assist patients identify the possibility of returning to work and/or education. The importance of programme flexibility was highlighted. PMID- 27563700 TI - Functional electrical stimulation versus ankle foot orthoses for foot-drop: A meta-analysis of orthotic effects. AB - OBJECTIVE: To compare the effects on walking of functional electrical stimulation (FES) and ankle foot orthoses for foot-drop of central neurological origin, assessed in terms of unassisted walking behaviours compared with assisted walking following a period of use (combined-orthotic effects). DATA SOURCES: MEDLINE, AMED, CINAHL, Cochrane Central Register of Controlled Trials, Scopus, REHABDATA, PEDro, NIHR Centre for Reviews and Dissemination and clinicaltrials.gov, plus reference list, journal, author and citation searches. STUDY SELECTION: English language comparative randomized controlled trials (RCTs). DATA SYNTHESIS: Seven RCTs were eligible for inclusion. Two of these reported different results from the same trial and another 2 reported results from different follow-up periods and were therefore combined, resulting in 5 synthesized trials with 815 stroke participants. Meta-analyses of data from the final assessment in each study and 3 overlapping time-points showed comparable improvements in walking speed over 10 m (p = 0.04-0.79), functional exercise capacity (p = 0.10-0.31), timed up-and-go (p = 0.812 and p = 0.539) and perceived mobility (p = 0.80) for both interventions. CONCLUSION: Data suggest that, in contrast to assumptions that predict FES superiority, ankle foot orthoses have equally positive combined-orthotic effects as FES on key walking measures for foot-drop caused by stroke. However, further long-term, high-quality RCTs are required. These should focus on measuring the mechanisms-of-action; whether there is translation of improvements in impairment to function, plus detailed reporting of the devices used across diagnoses. Only then can robust clinical recommendations be made. PMID- 27563701 TI - Scoring of Hand Eczema: Good Reliability of Hand Eczema Extent Score (HEES). AB - There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter- and intra observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a self-assessment twice. Inter- and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists' assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients' own assessments were 24.9 (range 4.0-54.0). Inter observer reliability in the dermatologists' observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists' ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients' 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema. PMID- 27563702 TI - Self-Inflicted Lesions in Dermatology: A Management and TherapeuticApproach - A Position Paper From the European Society for Derma-tology and Psychiatry. AB - The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new psychotherapies and psychotropic drugs without forgetting the most important relational characteristics required for dealing with people with these disorders. The management of self-inflicted skin lesions necessitates empathy and a doctor patient relationship based on trust and confidence. Cognitive behavioural therapy and/or psychodynamic and psychoanalytic psychotherapy (alone, or combined with the careful use of psychotropic drugs) seem to achieve the best results in the most difficult cases. Relatively new therapeutic techniques, such as habit reversal and mentalization-based psychotherapy, may be beneficial in the treatment of skin picking syndromes. PMID- 27563703 TI - Keloids, Spontaneous or After Minor Skin Injury: Importance of Not Missing Bethlem Myopathy. PMID- 27563704 TI - Chronic Pruritus in Primary Sjogren's Syndrome: Characteristics and Effect on Quality of Life. PMID- 27563705 TI - Interplay of mitochondrial metabolism and microRNAs. AB - Mitochondria are important organelles in cellular metabolism. Several crucial metabolic pathways such as the energy producing electron transport chain or the tricarboxylic acid cycle are hosted inside the mitochondria. The proper function of mitochondria depends on the import of proteins, which are encoded in the nucleus and synthesized in the cytosol. Micro-ribonucleic acids (miRNAs) are short non-coding ribonucleic acid (RNA) molecules with the ability to prevent messenger RNA (mRNA)-translation or to induce the degradation of mRNA transcripts. Although miRNAs are mainly located in the cytosol or the nucleus, a subset of ~150 different miRNAs, called mitomiRs, has also been found localized to mitochondrial fractions of cells and tissues together with the subunits of the RNA-induced silencing complex (RISC); the protein complex through which miRNAs normally act to prevent translation of their mRNA-targets. The focus of this review is on miRNAs and mitomiRs with influence on mitochondrial metabolism and their possible pathophysiological impact. PMID- 27563708 TI - Workers' Memorial Day - April 28, 2016. AB - Workers' Memorial Day, observed annually on April 28, recognizes workers who suffered or died because of exposures to hazards at work. In 2014, 4,679 U.S. workers died from work-related injuries. Although deaths from work-related injuries are captured by surveillance systems, most deaths from work-related illness are not. In 2007, an estimated 53,445 deaths from work-related illness occurred. In 2014, employers reported approximately 3 million nonfatal injuries and illnesses to private industry workers and 722,000 to state and local government workers; an estimated 2.7 million work-related injuries were treated in emergency departments, resulting in 113,000 hospitalizations (National Institute for Occupational Safety and Health (CDC-NIOSH), unpublished data, 2016). PMID- 27563709 TI - Moonlighting: Dip your toes. PMID- 27563710 TI - Q & A: Trade talk: Binational liaison. PMID- 27563706 TI - Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut. AB - Selenium is an essential micronutrient that is incorporated into at least 25 selenoproteins encoded by the human genome, many of which serve antioxidant functions. Because patients with inflammatory bowel disease (IBD) demonstrate nutritional deficiencies and are at increased risk for colon cancer due to heightened inflammation and oxidative stress, selenoprotein dysfunction may contribute to disease progression. Over the years, numerous studies have analyzed the effects of selenoprotein loss and shown that they are important mediators of intestinal inflammation and carcinogenesis. In particular, recent work has focused on the role of selenoprotein P (SEPP1), a major selenium transport protein which also has endogenous antioxidant function. These experiments determined SEPP1 loss altered immune and epithelial cellular function in a murine model of colitis-associated carcinoma. Here, we discuss the current knowledge of SEPP1 and selenoprotein function in the setting of IBD, colitis, and inflammatory tumorigenesis. PMID- 27563707 TI - Aptamer and its applications in neurodegenerative diseases. AB - Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathy, Huntington's disease and multiple sclerosis. PMID- 27563711 TI - Adopting Technology. PMID- 27563712 TI - The 2016 version of the gene table of monogenic neuromuscular disorders (nuclear genome). PMID- 27563713 TI - Author reply. PMID- 27563714 TI - ALK-positive anaplastic large-cell lymphoma with marked leukemoid reaction and hemophagocytic lymphohistiocytosis. PMID- 27563715 TI - Gallium(III)-Containing, Sandwich-Type Heteropolytungstates: Synthesis, Solution Characterization, and Hydrolytic Studies toward Phosphoester and Phosphoanhydride Bond Cleavage. AB - The gallium(III)-containing heteropolytungstates [Ga4(H2O)10(beta-XW9O33)2](6-) (X = As(III), 1; Sb(III), 2) were synthesized in aqueous acidic medium by reaction of Ga(3+) ions with the trilacunary, lone-pair-containing [XW9O33](9-). Polyanions 1 and 2 are isostructural and crystallized as the hydrated sodium salts Na6[Ga4(H2O)10(beta-AsW9O33)2].28H2O (Na-1) and Na6[Ga4(H2O)10(beta SbW9O33)2].30H2O (Na-2) in the monoclinic space group P21/c, with unit cell parameters a = 16.0218(12) A, b = 15.2044(10) A, c = 20.0821(12) A, and beta = 95.82(0) degrees , as well as a = 16.0912(5) A, b = 15.2178(5) A, c = 20.1047(5) A, and beta = 96.2(0) degrees , respectively. The corresponding tellurium(IV) derivative [Ga4(H2O)10(beta-TeW9O33)2](4-) (3) was also prepared, by direct reaction of sodium tungstate, tellurium(IV) oxide, and gallium nitrate. Polyanion 3 crystallized as the mixed rubidium/sodium salt Rb2Na2[Ga4(H2O)10(beta TeW9O33)2].28H2O (RbNa-3) in the triclinic space group P1 with unit cell parameters a = 12.5629(15) A, b = 13.2208(18) A, c = 15.474(2) A, alpha = 80.52(1) degrees , beta = 84.37(1) degrees , and gamma = 65.83(1) degrees . All polyanions 1-3 were characterized in the solid state by single-crystal XRD, FT IR, TGA, and elemental analysis, and polyanion 2 was also characterized in solution by (183)W NMR and UV-vis spectroscopy. Polyanion 2 was used as a homogeneous catalyst toward adenosine triphosphate (ATP) and the DNA model substrate 4-nitrophenylphosphate, monitored by (1)H and (31)P NMR spectroscopy. The encapsulated gallium(III) centers in 2 promote the Lewis acidic synergistic activation of the hydrolysis of ATP and DNA model substrates at a higher rate in near-physiological conditions. A strong interaction of 2 with the P-O bond of ATP was evidenced by changes in chemical shift values and line broadening of the (31)P nucleus in ATP upon addition of the polyanion. PMID- 27563716 TI - Study on the Diffusion-Dominated Solid-Phase Microextraction Kinetics in Semisolid Sample Matrix. AB - Solid-phase microextraction (SPME) kinetics in semisolid samples should be different from that in aqueous and gaseous samples, as convection is negligible in semisolid samples but dominates mass transfer in bulk phases of aqueous and gaseous samples. This study developed a mathematical model for describing SPME kinetics in semisolid samples by considering the diffusion of analytes in two compartments, i.e., the fiber coating and the ever-increasing diffusion domain in the sample matrix. The mathematical model predicted that SPME and the desorption of preloaded analytes from the fiber would be isotropic in semisolid samples, while SPME in semisolid samples would not follow the first order kinetics as in aqueous and gaseous samples. The predictions were proven true in the experiment of four pharmaceuticals in agarose gel. In return, it was observed in the experiment that SPME kinetics would deviate more significantly from the first order kinetics for the analytes with higher partition coefficients between the fiber and the sample matrix, which was well explained by the mathematical model developed in this study. In addition, SPME kinetics predicted by the model coincided well with the experimental results when the diffusion coefficients were at reasonable levels, which demonstrated that the model could be satisfactory for describing SPME kinetics in semisolid samples. The illustration of the nonfirst order SPME kinetics in semisolid samples can be valuable for evaluating the applicability of the existing pre-equilibrium calibration methods in semisolid samples. PMID- 27563717 TI - Compound Prioritization in Single-Concentration Screening Data Using Ligand Efficiency Indexes. AB - The triage of compounds at the single-concentration screening phase of high throughput screening (HTS) requires multiobjective optimization in order to achieve the best selection of hits, both in terms of potency and physicochemical properties, for a given number of compounds to test. In this regard, ligand efficiency indexes, well established as guides for hit prioritization in the dose response phase of HTS, are less studied in the single-concentration phase. In the present work the use of ligand efficiency indexes in the prioritization of compounds in single-concentration is investigated. Formulas for deriving them from single-concentration screening data are provided. The statistical association between the single-concentration and dose-response ligand efficiency indexes is evaluated with a wide historical data set including multiple screens of different target classes and screening technologies. The results show Pearson's correlation coefficients r above 0.9 for compounds with dose-response curves, and areas under the curve (AUC) of receiver operating characteristic (ROC) curves above 0.85 after including compounds with no dose-response curves. This good statistical association contains the contribution of both the physicochemical parameter(s) in the ligand efficiency indexes, as well as the biological activity, as demonstrated by permutation tests. The "cost/benefit" of using different thresholds of single-concentration ligand efficiency indexes in rescuing different numbers of efficient compounds is systematically investigated, and cost/benefit curves are provided. Approximate thresholds are proposed for the different ligand efficiency parameters that results in large percentages of efficient compounds rescued while attempting to reduce the cost of compounds to test in dose-response mode. Finally, a practical example of implementation of these indexes that considers clustering of compounds is described, where the rescue of efficient compounds is higher and with a much lower cost than a typical response-driven selection. PMID- 27563719 TI - Integration of Next Generation Sequencing and EPR Analysis to Uncover Molecular Mechanism Underlying Shell Color Variation in Scallops. AB - The Yesso scallop Patinopecten yessoensis displays polymorphism in shell colors, which is of great interest for the scallop industry. To identify genes involved in the shell coloration, in the present study, we investigate the transcriptome differences by Illumina digital gene expression (DGE) analysis in two extreme color phenotypes, Red and White. Illumina sequencing yields a total of 62,715,364 clean sequence reads, and more than 85% reads are mapped into our previously sequenced transcriptome. There are 25 significantly differentially expressed genes between Red and White scallops. EPR (Electron paramagnetic resonance) analysis has identified EPR spectra of pheomelanin and eumelanin in the red shells, but not in the white shells. Compared to the Red scallops, the White scallops have relatively higher mRNA expression in tyrosinase genes, but lower expression in other melanogensis-associated genes. Meantime, the relatively lower tyrosinase protein and decreased tyrosinase activity in White scallops are suggested to be associated with the lack of melanin in the white shells. Our findings highlight the functional roles of melanogensis-associated genes in the melanization process of scallop shells, and shed new lights on the transcriptional and post-transcriptional mechanisms in the regulation of tyrosinase activity during the process of melanin synthesis. The present results will assist our molecular understanding of melanin synthesis underlying shell color polymorphism in scallops, as well as other bivalves, and also help the color-based breeding in shellfish aquaculture. PMID- 27563718 TI - Clonal Evolution of Enterocytozoon bieneusi Populations in Swine and Genetic Differentiation in Subpopulations between Isolates from Swine and Humans. AB - Enterocytozoon bieneusi is a widespread parasite with high genetic diversity among hosts. Its natural reservoir remains elusive and data on population structure are available only in isolates from primates. Here we describe a population genetic study of 101 E. bieneusi isolates from pigs using sequence analysis of the ribosomal internal transcribed spacer (ITS) and four mini- and microsatellite markers. The presence of strong linkage disequilibrium (LD) and limited genetic recombination indicated a clonal structure for the population. Bayesian inference of phylogeny, structural analysis, and principal coordinates analysis separated the overall population into three subpopulations (SP3 to SP5) with genetic segregation of the isolates at some geographic level. Comparative analysis showed the differentiation of SP3 to SP5 from the two known E. bieneusi subpopulations (SP1 and SP2) from primates. The placement of a human E. bieneusi isolate in pig subpopulation SP4 supported the zoonotic potential of some E. bieneusi isolates. Network analysis showed directed evolution of SP5 to SP3/SP4 and SP1 to SP2. The high LD and low number of inferred recombination events are consistent with the possibility of host adaptation in SP2, SP3, and SP4. In contrast, the reduced LD and high genetic diversity in SP1 and SP5 might be results of broad host range and adaptation to new host environment. The data provide evidence of the potential occurrence of host adaptation in some of E. bieneusi isolates that belong to the zoonotic ITS Group 1. PMID- 27563720 TI - Efficient Reconstruction of Predictive Consensus Metabolic Network Models. AB - Understanding cellular function requires accurate, comprehensive representations of metabolism. Genome-scale, constraint-based metabolic models (GSMs) provide such representations, but their usability is often hampered by inconsistencies at various levels, in particular for concurrent models. COMMGEN, our tool for COnsensus Metabolic Model GENeration, automatically identifies inconsistencies between concurrent models and semi-automatically resolves them, thereby contributing to consolidate knowledge of metabolic function. Tests of COMMGEN for four organisms showed that automatically generated consensus models were predictive and that they substantially increased coherence of knowledge representation. COMMGEN ought to be particularly useful for complex scenarios in which manual curation does not scale, such as for eukaryotic organisms, microbial communities, and host-pathogen interactions. PMID- 27563721 TI - Being an identity-release donor: a qualitative study exploring the motivations, experiences and future expectations of current UK egg donors. AB - The objective of this study was to examine the motivations, experiences and future expectations of identity-release egg donors in the UK following the removal of donor anonymity and the increase in financial compensation for egg donation. This exploratory, in-depth qualitative study comprised semi-structured interviews with 11 women who had attended an egg donation screening appointment at a UK clinic during a four-month period in 2014. Interviews were conducted two to six weeks after the woman had donated or had withdrawn/been rejected from the donation process. Participants' primary motivation for donating was to help infertile women have their 'own child', and the recent increase in financial compensation did not seem to play a significant role in their decision. All were happy to be identifiable and contacted by children born as a result of their donation. However, some were hesitant about providing non-identifying information about themselves for these offspring and wished for further information about the recipient(s) of their eggs and the outcome of their donation. Whilst this study was limited due to the small sample size, it is the first study of UK egg donors following the rise in donor compensation and suggests that other strategies may be more effective in increasing donor numbers. PMID- 27563722 TI - Cranial Morphology of the Carboniferous-Permian Tetrapod Brachydectes newberryi (Lepospondyli, Lysorophia): New Data from uCT. AB - Lysorophians are a group of early tetrapods with extremely elongate trunks, reduced limbs, and highly reduced skulls. Since the first discovery of this group, general similarities in outward appearance between lysorophians and some modern lissamphibian orders (specifically Urodela and Gymnophiona) have been recognized, and sometimes been the basis for hypotheses of lissamphibian origins. We studied the morphology of the skull, with particular emphasis on the neurocranium, of a partial growth series of the lysorophian Brachydectes newberryi using x-ray micro-computed tomography (MUCT). Our study reveals similarities between the braincase of Brachydectes and brachystelechid recumbirostrans, corroborating prior work suggesting a close relationship between these taxa. We also describe the morphology of the epipterygoid, stapes, and quadrate in this taxon for the first time. Contra the proposals of some workers, we find no evidence of expected lissamphibian synapomorphies in the skull morphology in Brachydectes newberryi, and instead recognize a number of derived amniote characteristics within the braincase and suspensorium. Morphology previously considered indicative of taxonomic diversity within Lysorophia may reflect ontogenetic rather than taxonomic variation. The highly divergent morphology of lysorophians represents a refinement of morphological and functional trends within recumbirostrans, and is analogous to morphology observed in many modern fossorial reptiles. PMID- 27563723 TI - Adverse Mucocutaneous Reaction to Pertuzumab in a Patient with HER2-Positive Metastatic Breast Cancer. PMID- 27563724 TI - Strength Is in Numbers: Can Concordant Artificial Listeners Improve Prediction of Emotion from Speech? AB - Humans can communicate their emotions by modulating facial expressions or the tone of their voice. Albeit numerous applications exist that enable machines to read facial emotions and recognize the content of verbal messages, methods for speech emotion recognition are still in their infancy. Yet, fast and reliable applications for emotion recognition are the obvious advancement of present 'intelligent personal assistants', and may have countless applications in diagnostics, rehabilitation and research. Taking inspiration from the dynamics of human group decision-making, we devised a novel speech emotion recognition system that applies, for the first time, a semi-supervised prediction model based on consensus. Three tests were carried out to compare this algorithm with traditional approaches. Labeling performances relative to a public database of spontaneous speeches are reported. The novel system appears to be fast, robust and less computationally demanding than traditional methods, allowing for easier implementation in portable voice-analyzers (as used in rehabilitation, research, industry, etc.) and for applications in the research domain (such as real-time pairing of stimuli to participants' emotional state, selective/differential data collection based on emotional content, etc.). PMID- 27563725 TI - Distinct Bacterial Microbiomes in Sexual and Asexual Potamopyrgus antipodarum, a New Zealand Freshwater Snail. AB - Different reproductive strategies and the transition to asexuality can be associated with microbial symbionts. Whether such a link exists within mollusks has never been evaluated. We took the first steps towards addressing this possibility by performing pyrosequencing of bacterial 16S rRNA genes associated with Potamopyrgus antipodarum, a New Zealand freshwater snail. A diverse set of 60 tissue collections from P. antipodarum that were genetically and geographically distinct and either obligately sexual or asexual were included, which allowed us to evaluate whether reproductive mode was associated with a particular bacterial community. 2624 unique operational taxonomic units (OTU, 97% DNA similarity) were detected, which were distributed across ~30 phyla. While alpha diversity metrics varied little among individual samples, significant differences in bacterial community composition and structure were detected between sexual and asexual snails, as well as among snails from different lakes and genetic backgrounds. The mean dissimilarity of the bacterial communities between the sexual and asexual P. antipodarum was 90%, largely driven by the presence of Rickettsiales in sexual snails and Rhodobacter in asexual snails. Our study suggests that there might be a link between reproductive mode and the bacterial microbiome of P. antipodarum, though a causal connection requires additional study. PMID- 27563726 TI - Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development. AB - The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers-waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin-in mid-life. We used data from the Medical Research Council's National Survey of Health and Development-the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16-51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn't have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences ( 4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women. PMID- 27563727 TI - High pi-Facial and exo-Selectivity for the Intramolecular Diels-Alder Cycloaddition of Dodeca-3,9,11-trien-5-one Precursors to 2-epi-Symbioimine and Related Compounds. AB - An unconstrained exocyclic stereogenic center and a removable trimethylsilyl group are combined to induce high pi-facial selectivity and near-exclusive exo selectivity in the intramolecular Diels-Alder cycloaddition of dodeca-3,9,11 trien-5-ones. This strategy provides direct access to polysubstituted trans-1 decalones related to the symbioimines in good yield and acceptable diastereoselectivity. PMID- 27563729 TI - Schincalide A, a Schinortriterpenoid with a Tricyclo[5.2.1.0(1,6)]decane-Bridged System from the Stems and Leaves of Schisandra incarnate. AB - Schincalide A (1), an unprecedented schinortriterpenoid possessing a tricyclo[5.2.1.0(1,6)]decane-bridged system, was isolated from the stems and leaves of Schisandra incarnate. The structure with absolute configuration of 1 was determined by extensive spectroscopic analyses and single-crystal X-ray diffraction. A hypothetical biosynthetic pathway of 1 was postulated. PMID- 27563730 TI - Electrochemical Protein Cleavage in a Microfluidic Cell with Integrated Boron Doped Diamond Electrodes. AB - Specific electrochemical cleavage of peptide bonds at the C-terminal side of tyrosine and tryptophan generates peptides amenable to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis for protein identification. To this end we developed a microfluidic electrochemical cell of 160 nL volume that combines a cell geometry optimized for a high electrochemical conversion efficiency (>95%) with an integrated boron doped diamond (BDD) working electrode offering a wide potential window in aqueous solution and reduced adsorption of peptides and proteins. Efficient cleavage of the proteins bovine insulin and chicken egg white lysozyme was observed at 4 out of 4 and 7 out of 9 of the predicted cleavage sites, respectively. Chicken egg white lysozyme was identified based on 5 electrochemically generated peptides using a proteomics database searching algorithm. These results show that electrochemical peptide bond cleavage in a microfluidic cell is a novel, fully instrumental approach toward protein analysis and eventually proteomics studies in conjunction with mass spectrometry. PMID- 27563728 TI - RANK-Independent Osteoclast Formation and Bone Erosion in Inflammatory Arthritis. AB - OBJECTIVE: Proinflammatory molecules promote osteoclast-mediated bone erosion by up-regulating local RANKL production. However, recent evidence suggests that combinations of cytokines, such as tumor necrosis factor (TNF) plus interleukin-6 (IL-6), induce RANKL-independent osteoclastogenesis. The purpose of this study was to better understand TNF/IL-6-induced osteoclast formation and to determine whether RANK is absolutely required for osteoclastogenesis and bone erosion in murine inflammatory arthritis. METHODS: Myeloid precursors from wild-type (WT) mice or mice with either germline or conditional deletion of Rank, Nfatc1, Dap12, or Fcrg were treated with either RANKL or TNF plus IL-6. Osteoprotegerin, anti-IL 6 receptor (anti-IL-6R), and hydroxyurea were used to block RANKL, the IL-6R, and cell proliferation, respectively. Clinical scoring, histologic assessment, micro computed tomography, and quantitative polymerase chain reaction (qPCR) were used to evaluate K/BxN serum-transfer arthritis in WT and RANK-deleted mice. Loss of Rank was verified by qPCR and by osteoclast cultures. RESULTS: TNF/IL-6 generated osteoclasts in vitro that resorbed mineralized tissue through a pathway dependent on IL-6R, NFATc1, DNAX-activation protein 12, and cell proliferation, but independent of RANKL or RANK. Bone erosion and osteoclast formation were reduced, but not absent, in arthritic mice with inducible deficiency of RANK. TNF/IL-6, but not RANKL, induced osteoclast formation in bone marrow and synovial cultures from animals deficient in Rank. Multiple IL-6 family members (IL-6, leukemia inhibitory factor, oncostatin M) were up-regulated in the synovium of arthritic mice. CONCLUSION: The persistence of bone erosion and synovial osteoclasts in Rank-deficient mice, and the ability of TNF/IL-6 to induce osteoclastogenesis, suggest that more than one cytokine pathway exists to generate these bone resorbing cells in inflamed joints. PMID- 27563731 TI - Effects of TiO2 and TiC Nanofillers on the Performance of Dye Sensitized Solar Cells Based on the Polymer Gel Electrolyte of a Cobalt Redox System. AB - Polymer gel electrolytes (PGEs) of cobalt redox system are prepared for dye sensitized solar cell (DSSC) applications. Poly(vinylidene fluoride-co hexafluoropropylene) (PVDF-HFP) is used as a gelator of an acetonitrile (ACN) liquid electrolyte containing tris(2,2'-bipyridine)cobalt(II/III) redox couple. Titanium dioxide (TiO2) and titanium carbide (TiC) nanoparticles are utilized as nanofillers (NFs) of this PGE, and the effects of the two NFs on the conductivity of the PGEs, charge-transfer resistances at the electrode/PGE interface, and the performance of the gel-state DSSCs are studied and compared. The results show that the presence of TiC NFs significantly increases the conductivity of the PGE and decreases the charge-transfer resistance at the Pt counter-electrode (CE)/PGE interface. Therefore, the gel-state DSSC utilizing TiC NFs can achieve a conversion efficiency (6.29%) comparable to its liquid counterpart (6.30%), and, furthermore, the cell efficiency can retain 94% of its initial value after a 1000 h stability test at 50 degrees C. On the contrary, introduction of TiO2 NFs in the PGE causes a decrease of cell performances. It shows that the presence of TiO2 NFs increases the charge-transfer resistance at the Pt CE/PGE interface, induces the charge recombination at the photoanode/PGE interface, and, furthermore, causes a dye desorption in a long-term-stability test. These results are different from those reported for the iodide redox system and are ascribed to a specific attractive interaction between TiO2 and cobalt redox ions. PMID- 27563732 TI - Bimanual Capacity of Children With Cerebral Palsy: Intra- and Interrater Reliability of a Revised Edition of the Bimanual Fine Motor Function Classification. AB - AIMS: To develop a revised edition of the Bimanual Fine Motor Function (BFMF 2), as a classification of fine motor capacity in children with cerebral palsy (CP), and establish intra- and interrater reliability of this edition. METHODS: The content of the original BFMF was discussed by an expert panel, resulting in a revised edition comprising the original description of the classification levels, but in addition including figures with specific explanatory text. Four professionals classified fine motor function of 79 children (3-17 years; 45 boys) who represented all subtypes of CP and Manual Ability Classification levels (I V). Intra- and inter-rater reliability was assessed using overall intra-class correlation coefficient (ICC), and Cohen's quadratic weighted kappa. RESULTS: The overall ICC was 0.86. Cohen's weighted kappa indicated high intra-rater (kw: >0.90) and inter-rater (kw: >0.85) reliability. CONCLUSIONS: The revised BFMF 2 had high intra- and interrater reliability. The classification levels could be determined from short video recordings (<5 minutes), using the figures and precise descriptions of the fine motor function levels included in the BFMF 2. Thus, the BFMF 2 may be a feasible and useful classification of fine motor capacity both in research and in clinical practice. PMID- 27563733 TI - Near-Unity Absorption in van der Waals Semiconductors for Ultrathin Optoelectronics. AB - We demonstrate near-unity, broadband absorbing optoelectronic devices using sub 15 nm thick transition metal dichalcogenides (TMDCs) of molybdenum and tungsten as van der Waals semiconductor active layers. Specifically, we report that near unity light absorption is possible in extremely thin (<15 nm) van der Waals semiconductor structures by coupling to strongly damped optical modes of semiconductor/metal heterostructures. We further fabricate Schottky junction devices using these highly absorbing heterostructures and characterize their optoelectronic performance. Our work addresses one of the key criteria to enable TMDCs as potential candidates to achieve high optoelectronic efficiency. PMID- 27563734 TI - Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D. AB - Loxoscelism refers to the clinical symptoms that develop after brown spider bites. Brown spider venoms contain several phospholipase-D isoforms, which are the main toxins responsible for both the cutaneous and systemic effects of loxoscelism. Understanding of the phospholipase-D catalytic mechanism is crucial for the development of specific treatment that could reverse the toxic effects caused by the spider bite. Based on enzymatic, biological, structural, and thermodynamic tests, we show some features suitable for designing drugs against loxoscelism. Firstly, through molecular docking and molecular dynamics predictions, we found three different molecules (Suramin, Vu0155056, and Vu0359595) that were able to bind the enzyme's catalytic site and interact with catalytically important residues (His12 or His47) and with the Mg2+ co-factor. The binding promoted a decrease in the recombinant brown spider venom phospholipase-D (LiRecDT1) enzymatic activity. Furthermore, the presence of the inhibitors reduced the hemolytic, dermonecrotic, and inflammatory activities of the venom toxin in biological assays. Altogether, these results indicate the mode of action of three different LiRecDT1 inhibitors, which were able to prevent the venom toxic effects. This strengthen the idea of the importance of designing a specific drug to treat the serious clinical symptoms caused by the brown spider bite, a public health problem in several parts of the world, and until now without specific treatment. J. Cell. Biochem. 118: 726-738, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27563735 TI - The discovery of the lymphatic system in the seventeenth century. Part II: the discovery of Chyle vessels. AB - In the seventeenth century, opportunities to discover chyle came about through the revival of vivisection. Gaspare Aselli discovered chyle vessels in a living well-fed dog in 1622. He introduced the term 'lacteals' or milky veins. According to Aselli, the lacteals passed through a mesenteric gland which he called 'pancreas'. The 1627 edition of Aselli's booklet was the start of a 'lymphomania', which led to the dissection and vivisection of hundreds of animals, with the University of Leiden being the clear leader in this field. The prominent researchers in Leiden were Jacobus Sylvius and Johannes Walaeus, who performed diverse experiments to support Harvey's theories on systemic circulation, and to find out the correct anatomy and physiology of lacteals and mesenteric glands. Another centre of excellence was Padua, where Veslingius and Wirsung introduced the idea of the prominent role of the 'real pancreas', and its duct in the transformation of digested food into clear chyle. The idea of the transport of chyle to the liver was an additional support for Galen's theories regarding the function of the liver. Nevertheless, as time went on, there were fewer and fewer believers in Galenic doctrine. PMID- 27563737 TI - Deficits in the 30-Hz auditory steady-state response in patients with major depressive disorder. AB - The auditory steady-state response (ASSR) is an auditory evoked potential that occurs in response to periodically presented auditory stimuli. The ASSR has drawn attention as a biomarker of psychiatric disorders owing to its connection with neural oscillations as well as its easy and noninvasive recording. Abnormalities in the gamma band ASSR have been found consistently in patients with schizophrenia and bipolar disorder. However, although major depressive disorder (MDD) is also part of the common psychiatric diseases, the relationship between the ASSR and MDD has not been characterized sufficiently. Thus, the aim of the present study was to examine the ASSRs from patients with MDD and compare them with those from healthy control (HC) participants. The experiment was designed to obtain the ASSRs elicited by 20-, 30-, and 40-Hz click trains. Patients and HCs were evaluated separately. The response power and phase synchronization were measured at each stimulation frequency. Patients with MDD showed significantly reduced ASSR power for 30-Hz stimuli compared with HC participants, whereas no significant differences in the power were observed at 20 and 40 Hz for patients with MDD. In addition, no significant difference in the phase synchronization was observed for 20-, 30-, and 40-Hz stimuli. Conclusively, patients with MDD were characterized by deficits in 30-Hz ASSR power, which may be associated with spontaneous gamma activity dysfunction. The present findings suggest that ASSR could potentially be used as a biomarker for MDD. PMID- 27563736 TI - The role of trigeminal nucleus caudalis orexin 1 receptor in orofacial pain induced anxiety in rat. AB - The relationship between anxiety and pain has received special attention. Orexins (A and B) are hypothalamic neuropeptides that have diverse functions in the regulation of different physiological and behavioral responses. This study was designed to evaluate the role of orexin 1 receptors (OX1R) within trigeminal nucleus caudalis (TNC) in anxiety following the induction of orofacial pain. The subcutaneous injection of capsaicin (CAP) into the rat upper lip region produced pain responses. OX1R agonist (orexin A) and antagonist (SB-334867) were microinjected into the TNC before the administration of CAP. Anxiety behaviors were investigated using elevated plus maze (EPM) and open-field tests. The results showed that CAP injection significantly decreases the percentage of time spent in the open arms of the EPM and the time spent in the center of the open field. Surprisingly, orexin (50, 100, and 150 pM/rat) significantly exaggerated the CAP effects, whereas SB-334867 (20, 40 nM/rat) significantly inhibited the CAP-induced anxiety. The CAP-injected group showed a significant decrease in the percentage of entries to open arms in the EPM and the number of visits in the center area of the open field compared with the control group. Orexin significantly potentiated the mentioned effects of CAP, whereas SB-334867 (40, 80 nM/rat) exerted a significant inhibitory effect on CAP-induced anxiety. The overall results indicated that the TNC OX1Rs play an important role in orofacial pain-induced anxiety. PMID- 27563738 TI - The dysfunction of face processing in patients with internet addiction disorders: an event-related potential study. AB - To investigate face processing in patients with internet addiction disorders (IAD), an event-related brain potential experiment was conducted in IAD patients and healthy age-matched controls in which participants were instructed to classify each stimulus (face vs. nonface object) as quickly and accurately as possible. Although we did not find a significant difference in the performance between two groups, both the N110 and the P2 components in response to faces were larger in the IAD group than in the control group, whereas the N170 to faces decreased in the IAD group than in the control group. In addition, the source analysis of event-related potential components showed different generators between two groups. These data indicated that there was a dysfunction of face processing in IAD patients and the underlying mechanism of processing faces could be different from healthy individuals. PMID- 27563739 TI - Control of Electronic Symmetry and Rectification through Energy Level Variations in Bilayer Molecular Junctions. AB - Two layers of molecular oligomers were deposited on flat carbon electrode surfaces by electrochemical reduction of diazonium reagents, then a top contact applied to complete a solid-state molecular junction containing a molecular bilayer. The structures and energy levels of the molecular layers included donor molecules with relatively high energy occupied orbitals and acceptors with low energy unoccupied orbitals. When the energy levels of the two molecular layers were similar, the device had electronic characteristics similar to a thick layer of a single molecule, but if the energy levels differed, the current voltage behavior exhibited pronounced rectification. Higher current was observed when the acceptor molecule was biased negatively in eight different bilayer combinations, and the direction of rectification was reversed if the molecular layers were also reversed. Rectification persisted at very low temperature (7 K), and was activationless between 7 and 100 K. The results are a clear example of a "molecular signature" in which electronic behavior is directly affected by molecular structure and orbital energies. The rectification mechanism is discussed, and may provide a basis for rational design of electronic properties by variation of molecular structure. PMID- 27563740 TI - Do causes of stress differ in their association with problem drinking by sex in Korean adolescents? AB - BACKGROUND: Previous studies have focused mainly on whether stress causes present drinking or excessive drinking. However, few studies have been conducted on the relationship between stress and problem drinking in adolescents. The objective of this study was to examine the stress level and the cause of stress related to problem drinking behavior according to sex among Korean youth. METHOD: Data for this study were pooled from cross-sectional data collected annually from 2007 through 2012 from the Korea Youth Risk Behavior Web-based Survey. A representative sample of 442,113 students from 800 randomly selected middle and high schools in Korea were included. Multiple logistic regression models were used in the analysis. RESULTS: Both male and female students with extremely high stress were more likely to engage in problem drinking than were students with no stress (odds ratios [OR], 1.73 in males and 1.41 in females). The major causes of stress in male students that were associated with problem drinking were conflict with a teacher, trouble with parents, and peer relationships (ORs, 2.47, 1.72, and 1.71, respectively), whereas there are no statistically significant association between causes of stress and problem drinking among female students. Considering stress level, Male students with extremely high stress level were associated with problem drinking regardless of causes of stress, while Female students who felt extremely high levels of stress were more likely to engage in problem drinking due to stress from a conflict with parents, peer relationships, appearance, and financial difficulty (ORs, 1.53, 1.53, 1.46, and 1.47, respectively). CONCLUSION: Adolescents who engage in problem drinking may be affected by different causes of stress according to sex. Thus, appropriate approaches that reflect sex differences will be helpful to alleviate problem drinking in adolescents and educational authorities need to arrange more effective education program for drinking given positive associations between drinking education and problem drinking. PMID- 27563742 TI - The Advantages of Adding Hyaluronic Acid or Mannitol to Hypertonic Saline Inhalation Treatment in Cystic Fibrosis. PMID- 27563741 TI - Descriptive and injunctive network norms associated with nonmedical use of prescription drugs among homeless youth. AB - BACKGROUND: Nonmedical use of prescription drugs (NMUPD) among youth and young adults is being increasingly recognized as a significant public health problem. Homeless youth in particular are more likely to engage in NMUPD compared to housed youth. Studies suggest that network norms are strongly associated with a range of substance use behaviors. However, evidence regarding the association between network norms and NMUPD is scarce. We sought to understand whether social network norms of NMUPD are associated with engagement in NMUPD among homeless youth. METHODS: 1046 homeless youth were recruited from three drop-in centers in Los Angeles, CA and were interviewed regarding their individual and social network characteristics. Multivariate logistic regression was employed to evaluate the significance of associations between social norms (descriptive and injunctive) and self-reported NMUPD. RESULTS: Approximately 25% of youth reported past 30-day NMUPD. However, more youth (32.28%) of youth believed that their network members engage in NMUPD, perhaps suggesting some pluralistic ignorance bias. Both descriptive and injunctive norms were associated with self-reported NMUPD among homeless youth. However, these varied by network type, with presence of NMUPD engaged street-based and home-based peers (descriptive norm) increasing the likelihood of NMUPD, while objections from family-members (injunctive norm) decreasing that likelihood. CONCLUSIONS: Our findings suggest that, like other substance use behaviors, NMUPD is also influenced by youths' perceptions of the behaviors of their social network members. Therefore, prevention and interventions programs designed to influence NMUPD might benefit from taking a social network norms approach. PMID- 27563743 TI - A Class of Multiresponsive Colorimetric and Fluorescent pH Probes via Three Different Reaction Mechanisms of Salen Complexes: A Selective and Accurate pH Measurement. AB - We report a class of multiresponsive colorimetric and fluorescent pH probes based on three different reaction mechanisms including cation exchange, protonation, and hydrolysis reaction of K(I), Ca(II), Zn(II), Cu(II), Al(III), and Pd(II) Salen complexes. Compared with traditional pure organic pH probes, these complex based pH probes exhibited a much better selectivity due to the shielding function of the filled-in metal ion in the complex. Their pH sensing performances were affected by the ligand structure and the central metal ion. This work is the first report of "off-on-on'-off" colorimetric and fluorescent pH probes that possess three different reaction mechanisms and should inspire the design of multiple-responsive probes for important analytes in biological systems. PMID- 27563744 TI - 2017 Clinical trials update: Innovations in hemophilia therapy. AB - A surge in therapeutic clinical trials over recent years is paving the way for transformative treatment options for patients with hemophilia. The introduction of recombinant factor concentrates in the early 1990s facilitated the use of prophylactic replacement as standard care for hemophilia rather than on-demand treatment. This has revolutionized health outcomes for hemophilia patients, enabling participation in physical activities and reducing debilitating, chronic joint damage. Challenges of prophylactic factor infusion include the frequency of infusions needed to maintain factor levels greater than 1%, patient adherence, reliable intravenous access, and development of neutralizing alloantibodies ("inhibitors"). Novel therapeutics seek to improve upon current factor concentrates by several different mechanisms: (1) extending the half-life of circulating exogenous factor protein, (2) replacing the gene necessary for production of endogenous factor protein, (3) employing bispecific antibody technology to mimic the coagulation function of factor VIII, (4) disrupting anticoagulant proteins, such as tissue factor pathway inhibitor (TFPI) or antithrombin (AT3) with antibodies, aptamers, or RNA interference technology. Emerging treatment options may reduce the frequency of (extended half-life products) or eliminate (gene therapy) the need for scheduled factor concentrate infusions, or provide a subcutaneous administration option (bispecific antibody, AT3, and TFPI targeting therapies). In addition, the nonfactor replacement strategies provide a promising treatment option for patients with inhibitors, presently the greatest unmet medical need in hemophilia. This review highlights current and recently completed clinical trials that are driving a paradigm shift in our approach to hemophilia care for patients with and without inhibitors. Am. J. Hematol. 91:1252-1260, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27563746 TI - Early history of circular RNAs, children of splicing. AB - In this commentary we briefly summarize early work on circular RNAs derived from spliceosome mediated circularization. We highlight how this early work inspired work on the basic mechanisms of nuclear RNA splicing, the possible function of circular RNAs and the potential uses of circular RNAs as tools in biomedicine. Recent developments in the study of circular RNAs, summarized in this volume, have brought these questions back to the foreground. PMID- 27563747 TI - Decolonisation of meticillin-resistant Staphylococcus aureus (MRSA) carriage in adopted children with cleft lip and palate. AB - This study aimed to determine the percentage success and to investigate influencing factors of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation treatment in children with cleft lip and/or palate (CLP) who are adopted to The Netherlands. This was a historic cohort study in nine Dutch hospitals with a CLP treatment centre of children who were adopted from abroad in 2005-2012 who had CLP and MRSA carriage upon arrival in The Netherlands. A total of 55 adopted children with CLP and MRSA carriage were eligible for the study. Most children were adopted from China and had cheilognathopalatoschisis. Fourteen children were not treated for MRSA carriage, of whom six became MRSA-negative spontaneously. Forty-one children received decolonisation treatment (either topical treatment and disinfectant body wash or these combined with oral antibiotics). Overall, eighteen children [44%; 95% confidence interval (CI) 29 59%] became MRSA-negative after treatment. Treatment success was higher (56%; 95% CI 33-77%) in the group of children treated according to the Dutch guideline for treatment of MRSA carriage (odds ratio=6.1, 95% CI 4.4-26.4; p=0.017). In conclusion, MRSA decolonisation treatment in adopted children with CLP was successful in 44% of cases and the success percentage was higher in the group of children treated in accordance with the national guideline for treatment of MRSA carriage. However, given the percentage of children who turned MRSA-negative without treatment, waiting for spontaneous clearance of MRSA carriage can be advised after careful consideration of the benefits and risks of decolonisation treatment. PMID- 27563745 TI - Baclofen in the Therapeutic of Sequele of Traumatic Brain Injury: Spasticity. AB - Traumatic brain injury (TBI) is an alteration in brain function, caused by an external force, which may be a hit on the skull, rapid acceleration or deceleration, penetration of an object, or shock waves from an explosion. Traumatic brain injury is a major cause of morbidity and mortality worldwide, with a high prevalence rate in pediatric patients, in which treatment options are still limited, not available at present neuroprotective drugs. Although the therapeutic management of these patients is varied and dependent on the severity of the injury, general techniques of drug types are handled, as well as physical and surgical. Baclofen is a muscle relaxant used to treat spasticity and improve mobility in patients with spinal cord injuries, relieving pain and muscle stiffness. Pharmacological support with baclofen is contradictory, because disruption of its oral administration may cause increased muscle tone syndrome and muscle spasm, prolonged seizures, hyperthermia, dysesthesia, hallucinations, or even multisystem organ failure. Combined treatments must consider the pathophysiology of broader alterations than only excitation/inhibition context, allowing the patient's reintegration with the greatest functionality. PMID- 27563748 TI - Prevalence of O25b-ST131 clone among Escherichia coli strains producing CTX-M-15, CTX-M-14 and CTX-M-92 beta-lactamases. AB - BACKGROUND: Dissemination of multidrug-resistant Escherichia coli is closely associated with the worldwide spread of a single clone ST131, which is the main cause of urinary tract and bloodstream infections in patients from nursing homes and immunocompromised patients. The aim of our study was to determine the prevalence of ST131 clone and the replicons involved in the spread of blaCTX-M genes among O25b-ST131 CTX-M-producing E. coli isolates in Lithuania. METHODS: The strains included in this study were screened for CTX-M beta-lactamase encoding genes, phylogenetic groups and ST131 clone by PCR. Bacterial conjugation was performed to identify plasmid replicon types responsible for blaCTX-M genes dissemination. RESULTS: A total of 158 E. coli clinical non-duplicate ESBL isolates were analyzed. Nearly half (n = 67, 42.4%) of the investigated E. coli isolates belonged to phylogenetic group B2. The isolates producing CTX-M-92 beta lactamases were identified to be the ST131 clone more frequently than the non ST131 clone (11.5% vs. 3.1%, p = .035). The CTX-M-15 isolates were identified as ST131 isolates less frequently than non-ST131 isolates (50.8% vs. 71.1%; p = .015). The ST131 clone isolates contained type L/M and A/C replicons; a fused FII/FIB replicon was found in four isolates (23.5%). Type HI1 replicon was identified in ST131 E. coli isolates producing CTX-M-15 beta-lactamases. CONCLUSIONS: This study demonstrates the predominance of the ST131 clone among CTX-M beta-lactamase-producing E. coli isolates. Dissemination of blaCTX-M genes in ST131 strains can be linked not only to highly adapted IncF plasmids such as FII/FIB and FII, but also to plasmid replicon types A/C, L/M and HI1. PMID- 27563749 TI - New insight into determining indicators of metabolic status in women: Expression of PPARgamma and FABP4 in PBMCs. AB - Adiposity and its metabolic disturbances could be regulated by adipocyte-specific peroxisome proliferator-activated receptor gamma and fatty acid-binding protein4. Although these two proteins are mainly expressed in adipose tissues, they can also be expressed in peripheral blood mononuclear cells, which could be useful for predicting body composition and blood parameters. Thus, this cross-sectional study was performed during January 2013-January 2014 with 229 women (age range, 22-52 years) who were classified as obese or nonobese. Serum glucose, insulin, lipids, and body composition were measured in the fasting state. Peripheral blood mononuclear cells were isolated to extract ribonucleic acid (RNA) and to determine gene expression by real time polymerase chain reaction (PCR). All serum parameters and components of body composition were significantly higher in obese than in nonobese women. Gene expression analysis showed that serum levels of glucose and lipids, except high-density lipoprotein (HDL), were higher in the group that expressed high fatty acid-binding protein4. Increased expression of the peroxisome proliferator-activated receptor gamma was associated with a significant reduction of blood sugar and increased HDL and other lipids and visceral fat. Therefore, it seems that the level of expression of these genes in peripheral blood mononuclear cells may indicate metabolic status. PMID- 27563750 TI - Graphene Oxide-Silver Nanocomposite: Novel Agricultural Antifungal Agent against Fusarium graminearum for Crop Disease Prevention. AB - Nanoparticle-based antibacterial agents have emerged as an interdisciplinary field involving medicine, material science, biology, and chemistry because of their size-dependent qualities, high surface-to-volume ratio, and unique physiochemical properties. Some of them have shown great promise for their application in plant protection and nutrition. Here, GO-AgNPs nanocomposite was fabricated through interfacial electrostatic self-assembly and its antifungal activity against phytopathogen Fusarium graminearum was investigated in vitro and in vivo for the first time. The results demonstrated that the GO-AgNPs nanocomposite showed almost a 3- and 7-fold increase of inhibition efficiency over pure AgNPs and GO suspension, respectively. The spore germination inhibition was stimulated by a relatively low concentration of 4.68 MUg/mL (minimum inhibition concentration (MIC)). The spores and hyphae were damaged, which might be caused by an antibacterial mechanism from the remarkable synergistic effect of GO-AgNPs, inducing physical injury and chemical reactive oxygen species generation. More importantly, the chemical reduction of GO mediated by fungal spores was possibly contributed to the high antimicrobial activity of GO-AgNPs. Furthermore, the GO-AgNPs nanocomposite showed a significant effect in controlling the leaf spot disease infected by F. graminearum in the detached leaf experiment. All the results from this research suggest that the GO-AgNPs nanocomposite developed in this work has the potential as a promising material for the development of novel antimicrobial agents against pathogenic fungi or bacteria. PMID- 27563752 TI - A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice, key challenges, and recommendations for the future. AB - OBJECTIVES: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain. METHODS: The search strategy was designed to identify peer-reviewed cost effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines. RESULTS: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled. CONCLUSIONS: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged. PMID- 27563751 TI - An Innovative Approach to Health Care Delivery for Patients with Chronic Conditions. AB - Although the health care reform movement has brought about positive changes, lingering inefficiencies and communication gaps continue to hamper system-wide progress toward achieving the overarching goal-higher quality health care and improved population health outcomes at a lower cost. The multiple interrelated barriers to improvement are most evident in care for the population of patients with multiple chronic conditions. During transitions of care, the lack of integration among various silos and inadequate communication among providers cause delays in delivering appropriate health care services to these vulnerable patients and their caregivers, diminishing positive health outcomes and driving costs ever higher. Long-entrenched acute care-focused treatment and reimbursement paradigms hamper more effective deployment of existing resources to improve the ongoing care of these patients. New models for care coordination during transitions, longitudinal high-risk care management, and unplanned acute episodic care have been conceived and piloted with promising results. Utilizing existing resources, Mobile Integrated Healthcare is an emerging model focused on closing these care gaps by means of a round-the-clock, technologically sophisticated, physician-led interprofessional team to manage care transitions and chronic care services on-site in patients' homes or workplaces. PMID- 27563754 TI - Chiroptical Properties of Streptorubin B: The Synergy Between Theory and Experiment. PMID- 27563753 TI - Simple Isocratic HPLC Method for Determination of Enantiomeric Impurity in Besifloxacin Hydrochloride. AB - Besifloxacin is a unique chiral broad-spectrum flouroquinolone used in the treatment of bacterial conjunctivitis. R-form of besifloxacin hydrochloride shows higher antibacterial activity as compared to the S-isomer. Therefore, it is necessary to establish chiral purity. To establish chiral purity a high performance liquid chromatography (HPLC) method for determination of R besifloxacin and S-besifloxacin (BES impurity A) was developed and validated for in-process quality control and stability studies. The analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD), and lower limit of quantification (LOQ) were determined according to International Council for Harmonization ICH Q2(R1) guidelines. HPLC separation was achieved on Chiralpak AD-H (250 x 4.6 mm, 5 MUm) column using n heptane: ethanol: ethylenediamine: acetic acid (800:200:0.5:0.5) (v/v/v/v) as the mobile phase in an isocratic elution. The eluents were monitored by UV/Visible detector at 290 nm. The resolution between S-isomer and besifloxacin hydrochloride was more than 2.0. Based on a signal-to-noise ratio of 3 and 10 the LOD of besifloxacin was 0.30 MUg/mL, while the LOQ was 0.90 MUg/mL. The calibration curves were linear in the range of 0.9-7.5 MUg/mL. Precision of the method was established within the acceptable range. The method was suitable for the quality control enantiomeric impurity in besifloxacin hydrochloride. Chirality 28:628-632, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27563755 TI - Uric acid transporters hiding in the intestine. AB - CONTEXT: Hyperuricaemia is known as an abnormally increased uric acid level in the blood. Although it was observed many years ago, since uric acid excretion via the intestine pathway accounted for approximately one-third of total elimination of uric acid, the molecular mechanism of 'extra-renal excretion' was poorly understood until the finding of uric acid transporters. OBJECTIVE: The objective of this study was to gather all information related to uric acid transporters in the intestine and present this information as a comprehensive and systematic review article. METHODS: A literature search was performed from various databases (e.g., Medline, Science Direct, Springer Link, etc.). The key terms included uric acid, transporter and intestine. The period for the search is from the 1950s to the present. The bibliographies of papers relating to the review subject were also searched for further relevant references. RESULTS: The uric acid transporters identified in the intestine are discussed in this review. The solute carrier (SLC) transporters include GLUT9, MCT9, NPT4, NPT homolog (NPT5) and OAT10. The ATP binding cassette (ABC) transporters include ABCG2 (BCRP), MRP2 and MRP4. Bacterial transporter YgfU is a low-affinity and high-capacity transporter for uric acid. CONCLUSION: The present review may be helpful for further our understanding of hyperuricaemia and be of value in designing future studies on novel therapeutic pathways. PMID- 27563756 TI - Fishing in acid waters: A vulnerability assessment of the Norwegian fishing industry in the face of increasing ocean acidification. AB - Ocean acidification (OA) describes a change in the ocean's carbonate chemistry. Whereas its chemical processes are largely understood, the biological and socioeconomic consequences particularly in relation to fisheries are less known. Norway is a major fishing nation worldwide and is potentially affected by OA. To improve the understanding of the socioeconomic consequences of OA, we conducted a risk assessment among the Norwegian counties using a modified version of a risk assessment framework introduced in the Intergovernmental Panel on Climate Change's "Special Report: Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation," which considers risk to be the sum of hazard, exposure, and vulnerability. Our results show that about 13 of 19 counties are likely to experience moderate to high risk from OA. We highlight that the success of integrated risk assessments highly depends on the availability of detailed environmental, economic, and societal data. In the case of Norway, modeling data regarding the progress of OA, improved information on potential biological impacts on a larger number of species, and statistical data on social variables are required. We conclude that although still in its infancy, integrated risk assessments are important prerequisites for any form of interdisciplinary research on OA and the development of successful response strategies. Integr Environ Assess Manag 2017;13:778-789. (c)2016 SETAC. PMID- 27563800 TI - Repellence of the main components from the essential oil of Glycosmis lucida Wall. ex Huang against two stored product insects. AB - A screening of Chinese medicinal herbs and wild plants for agrochemicals was carried out; the essential oil of Glycosmis lucida leaves was found to possess significant repellent activity against Tribolium castaneum and Liposcelis bostrychophila. It was found that the main components included elixene (19.81%), spathulenol (10.68%), anethole (12.05%), verbenone (10.32%) followed by beta caryophyllene (6.87%). The essential oil, anethole and verbenone were strongly repellent against T. castaneum (96, 86 and 94%, respectively, at 15.73 nL cm-2) and L. bostrychophila (100, 68 and 72%, respectively, at 31.58 nL cm-2) after a 2h treatment. The results indicate that anethole and verbenone had the potential to be developed as natural repellents for control of stored product insects. PMID- 27563802 TI - Rasburicase for Tumor Lysis Syndrome. PMID- 27563801 TI - Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome. AB - BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a constellation of signs and symptoms that occur when a patient is upright and relieved by recumbence. Currently, no drugs are labeled for the treatment for POTS. Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance. STUDY QUESTION: To appraise the effect of Droxidopa in a clinical setting in patients with POTS refractory to other forms of treatment. STUDY DESIGN: A retrospective study of patients with POTS at our Syncope and Autonomic Disorders Center. Three hundred fifty-two patients were screened, 54 of them were prescribed Droxidopa and found to be eligible to include in our study. MEASURES AND OUTCOME: Symptoms of orthostatic intolerance, side effects of therapy and response to treatment. Statistical analyses were done using SPSS software. Thirty seven patients were included in data analysis. Patients who failed to follow up, didn't obtain Droxidopa due to insurance and cost concerns, had hypertensive response to therapy or had allergic reaction were excluded from data analysis. RESULTS: The most frequently reported symptom was dizziness in 91.9% of patients, followed by syncope and fatigue in 70.3% and 67.6% of patients, respectively. Symptoms of dizziness, syncope and fatigue were reported less after treatment; 75.7%, 51.4% and 40.5%, respectively. There was no statistically significant difference in standing or sitting blood pressure before and after treatment. Despite the improvement in some symptoms. Only 27% of patients reported improved quality of life after treatment. Of total, 40.5% of patients stopped the treatment either due to side effects or ineffectiveness. CONCLUSION: Droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS but has diminutive impact on quality of life and blood pressure. Further assessment in large clinical trials is needed to evaluate its efficacy. PMID- 27563803 TI - Charge-Induced Long-Range Order in a Room-Temperature Ionic Liquid. AB - We report direct evidence for charge-induced long-range (ca. 100 MUm) order in the room-temperature ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM(+)BF4(-)), supported on a silica surface. We have measured the rotational diffusion dynamics of anionic, cationic, and neutral chromophores as a function of distance from a silica surface. The results reflect the excess charge density gradient induced in the IL by the (negative) charge present on the silica surface. Identical measurements in ethylene glycol reveal spatially invariant reorientation dynamics for all chromophores. Capping the silica support with Me2SiCl2 results in spatially invariant reorientation dynamics in the IL. We understand these data in the context of the IL exhibiting a spatially damped piezoelectric response mediated by IL fluidity and disorder. PMID- 27563804 TI - Prevention of Transition Metal Dichalcogenide Photodegradation by Encapsulation with h-BN Layers. AB - Transition metal dichalcogenides (TMDs) have recently received increasing attention because of their potential applications in semiconducting and optoelectronic devices exhibiting large optical absorptions in the visible range. However, some studies have reported that the grain boundaries of TMDs can be easily degraded by the presence of oxygen in water and by UV irradiation, ozone, and heating under ambient conditions. We herein demonstrate the photodegradation of WSe2 and MoSe2 by laser exposure (532 nm) and the subsequent prevention of this photodegradation by encapsulation with hexagonal boron nitride (h-BN) layers. The photodegradation was monitored by variation in peak intensities in the Raman and photoluminescence spectra. The rapid photodegradation of WSe2 under air occurred at a laser power of >=0.5 mW and was not observed to any extent at <=0.1 mW. However, in the presence of a water droplet, the photodegradation of WSe2 was accelerated and took place even at 0.1 mW. We examined the encapsulation of WSe2 with h-BN and found that this prevented photodegradation. However, a single layer of h-BN was not sufficient to fully prevent this photodegradation, and so a triple layer of h-BN was employed. We also demonstrated that the photodegradation of MoSe2 was prevented by encapsulation with h-BN layers. On the basis of X-ray photoelectron spectroscopy and scanning photoemission microscopy data, we determined that this degradation was caused by the photoinduced oxidation of TMDs. These results can be used to develop a general strategy for improving the stability of 2D materials in practical applications. PMID- 27563805 TI - (99m)Tc-3PRGD2 SPECT/CT Imaging for Monitoring Early Response of EGFR-TKIs Therapy in Patients with Advanced-Stage Lung Adenocarcinoma. AB - OBJECTIVE: This study was aimed to assess the efficacy of (99m)Tc-3PRGD2 imaging for evaluating both early treatment response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and prognosis in advanced-stage lung adenocarcinoma. MATERIAL AND METHODS: Eighteen patients with lung adenocarcinoma were enrolled for EGFR-TKIs therapy. (99m)Tc-3PRGD2 SPECT/CT and planar imaging were performed pre- and post-therapy. The tumor to nontumor (T/NT) ratio and percentage change in T/NT ratio were assessed for the treatment response. Receiver operator characteristic (ROC) analysis was utilized to analyze the power of identifying responders based on the changes in T/NT ratios. RESULTS: After treatment, 10 patients had partial response (PR), and 6 patients stable disease (SD), while 2 patients progressive disease (PD). The mean changes in T/NT ratios on SPECT/CT and planar images in PR group were 35.8% and 15.0% and in SD group were 8.9% and 0.7%, while in PD group were 76.1% and 18.7%, respectively. For ROC analysis, using a cutoff value of 23.8% decrease in T/NT ratio on SPECT/CT images, the sensitivity and specificity in identifying responders were 80.0% and 87.5%, respectively. The median progression-free survival (PFS) for patients with responders and nonresponders (on (99m)Tc-3PRGD2 SPECT/CT) was 18 months (95% CI 5.8-30.2 months) and 7 months (95% CI 5.2-8.8 months), respectively (p = 0.006). CONCLUSION: (99m)Tc-3PRGD2 imaging can evaluate the early response to EGFR targeted therapy and predict the PFS of lung adenocarcinoma patients. PMID- 27563806 TI - Progression of Voice Breaks in a Nonpathological Voice as an Indicator of Aerodigestive Health. PMID- 27563807 TI - Prognostic value of microRNA-9 in cancers: a systematic review and meta-analysis. AB - Recent studies revealed that different microRNA-9 (miR-9) expressions were associated with prognoses of different cancers. We conducted this meta-analysis to evaluate the prognostic value of miR-9. PubMed, Embase, Web of Science, and Cochrane Library (last update by November 30, 2015) were searched for literatures. A total of 17 studies from 16 articles were finally qualified and enrolled in this meta-analysis. Pooled analyses showed that a higher expression of miR-9 might predict poor overall survival (HR: 2.17, 95% CI: 1.39 - 3.41, P < 0.001 (7.23 * 10-4)), disease-free survival (HR: 5.22, 95% CI: 2.17 - 12.53, P < 0.001 (2.21 * 10-4)), and recurrence-free survival (HR: 1.57, 95% CI: 1.32 - 1.85, P < 0.001 (1.80*10-7)) in various carcinomas. However, results of subgroup analyses revealed that down-regulated miR-9 was associated with poor overall survival (HR: 0.45, 95% CI: 0.28 - 0.73, P < 0.001 (1.13*10-3)) and progress-free survival (HR: 0.46, 95% CI: 0.34 - 0.62, P < 0.001 (5.03*10-7)) in ovarian cancer patients. By subgroup analyses we also found that sample collecting time and patients' origin had little influence on the result of OS. These results indicate that in most cancer types the highly expressed miR-9 is associated with poor survival of patients, whereas the down-regulated miR-9 may predict poor prognosis in patients with ovarian cancer. PMID- 27563808 TI - NOD2 up-regulates TLR2-mediated IL-23p19 expression via NF-kappaB subunit c-Rel in Paneth cell-like cells. AB - IL-23p19 plays important roles in intestinal antimicrobial immunity, while its over-expression can lead to intestinal inflammation. However, the bacterial compounds and the type of pattern recognition receptor involved in the inducible expression of IL-23p19 in Paneth cells remain unclear. Here we show that the mRNA expression of IL-23p19 was increased in Paneth cell (PC)-like cells stimulated by Toll-like receptor 2 (TLR2) ligands, peptidoglycan (PGN) and Pam3CSK4, and was further increased in the presence of nucleotide-binding oligomerization domain 2 (NOD2)-ligand muramyl dipeptide (MDP). However, its mRNA expression was decreased in NOD2-knockdown PC-like cells. Additionally, the c-Rel activation was increased in Pam3CSK4- or PGN-stimulated PC-like cells, but the PGN-induced c-Rel activation was decreased in NOD2-knockdown PC-like cells and had no significant difference compared with Pam3CSK4-induced c-Rel activation. Our results suggest that NOD2 up-regulates TLR2-mediated IL-23p19 expression via increasing c-Rel activation in PC-like cells. This finding might provide us with a novel therapeutic target for inflammatory bowel disease to inhibit IL-23p19 over expression via the NOD2-c-Rel pathway. PMID- 27563810 TI - Efficacy of bortezomib in sarcomas with high levels of MAP17 (PDZK1IP1). AB - Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients with metastatic disease are treated with systemic chemotherapy. Many tumors display marginal levels of chemoresponsiveness, and new treatment approaches are needed. MAP17 is a small non-glycosylated membrane protein overexpressed in carcinomas. The levels of MAP17 could be used as a prognostic marker to predict the response to bortezomib in hematological malignancies and in breast tumors. Therefore, we analyzed the expression of this oncogene in sarcomas and its relationship with clinico-pathological features, as well as tested whether it can be used as a new biomarker to predict the therapeutic response to bortezomib and new therapies for sarcomas. We found that the levels of MAP17 were related to clinical features and poor survival in a cohort of 69 patients with different sarcoma types, not being restricted to any special subtype of tumor. MAP17 expression is associated with poor overall survival (p<0.001) and worse disease-free survival (p=0.002). Cell lines with high levels of MAP17 show a better response to bortezomib in vitro. Furthermore, patient-derived xenografts (PDX) with high levels of MAP17 respond to bortezomib in vivo. Our results showed that this response is due to the lower levels of NFkappaB and autophagy activation. Therefore, we suggest that MAP17 is a new biomarker to predict the efficacy of bortezomib as a new therapy for sarcomas. PMID- 27563811 TI - Prognostic significance and the role in TNM stage of extranodal metastasis within regional lymph nodes station in gastric carcinoma. AB - The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p<0.05) than ENMN group in all patients, TNM I-II stages and TNM III stage. ENM>2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage. PMID- 27563812 TI - New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity. AB - Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA database indicated that high OPN expression correlated with poor survival in GBM patients. In this study, we explored the role of OPN in GBM radioresistance using an OPN-depletion strategy in U87-MG, U87-MG vIII and U251-MG human GBM cell lines. Clonogenic experiments showed that OPN-depleted GBM cells were sensitized to irradiation. In comet assays, these cells displayed higher amounts of unrepaired DNA fragments post-irradiation when compared to control. We next evaluated the phosphorylation of key markers of DNA double-strand break repair pathway. Activating phosphorylation of H2AX, ATM and 53BP1 was significantly decreased in OPN deficient cells. The addition of recombinant OPN prior to irradiation rescued phospho-H2AX foci formation thus establishing a new link between DNA repair and OPN expression in GBM cells. Finally, OPN knockdown improved mice survival and induced a significant reduction of heterotopic human GBM xenograft when combined with radiotherapy. This study reveals a new function of OPN in DNA damage repair process post-irradiation thus further confirming its major role in GBM aggressive disease. PMID- 27563813 TI - Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins. AB - INTRODUCTION: Multiple myeloma is still incurable in most cases. Polyclonal anti T lymphocyte globulins (ATG) have been reported to kill human myeloma cells in vitro and in mouse models. METHODS: Anti-human-myeloma globulins (AMG) were produced by immunizing rabbits with human myeloma cell lines RPMI-8226 (AMG-8226) or KMS-12-BM (AMG-12-BM). Cytotoxicity of the polyclonal antibodies was analyzed in vitro and in a xenograft NOD-SCID mouse model. RESULTS: Both AMG had stronger cytotoxicity against myeloma cells compared to ATG. In primary T cells, AMG-8226 showed greater complement-dependent cytotoxicity (CDC) than ATG, whereas complement-independent cytotoxicity did not differ. Effects on non-hematopoietic cell lines were also similar. Competitive blocking assays revealed fourfold more antibodies against CD38 in AMG-8226 compared to ATG. Low concentrations of AMG 8226 and ATG increased ADCC. At higher concentrations, ATG inhibited ADCC more potently than AMG-8226. Combinations of ATG and AMG-8226 with melphalan or bortezomib showed additive to synergistic cytotoxicity on myeloma cells. The cytotoxic effects of AMG and ATG were confirmed in the xenograft NOD-SCID mouse model. CONCLUSION: Our data show more potent antimyeloma effects of AMG compared to ATG. These results lay the ground for the development of polyclonal antibodies for the treatment of multiple myeloma. PMID- 27563814 TI - Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. AB - The mechanistic target of rapamycin (mTOR) is a rational target for cancer treatment. While the mTORC1-selective rapalogs have shown significant benefits in the clinic, antitumor response may be further improved by inhibiting both mTORC1 and mTORC2. Herein, we established target profile of a novel mTOR kinase inhibitor (mTOR-KI) MTI-31 and employed it to study new therapeutic mechanism in breast cancer. MTI-31 demonstrated a potent mTOR binding affinity with >5000 fold selectivity over the related PI3K family isoforms. MTI-31 inhibited mTORC1- and mTORC2 function at <=120 nM in cellular assays or 5 mg/kg orally in tumor-bearing mice. In a panel of breast cancer lines, the antitumor efficacy of MTI-31 was dependent on HER2+ and/or PIK3CAmut (HER2+/PIK3CAmut) status of the tumors and required mTORC2-specific modulation of Bim, MCL-1 and GSK3. Inactivation of Bim or GSK3 each attenuated apoptotic death resulting in mTOR-KI resistance. The antitumor response also required a suppression of lipid metabolism in therapy sensitive tumors. Treatment with MTI-31 or AZD8055 substantially reduced lipogenesis and acetyl-CoA homeostasis, which was mechanistically linked to a blockade of mTORC2-dependent glucose-to-lipid conversion rate. We also found that the basal levels of carnitine palmitoyltransferase 1A and lipid catabolism were elevated in HER2+/PIK3CAmut breast cells and were inhibited upon mTOR-KI treatment. A CPT1A inhibitor etomoxir mimicked MTI-31 action in selective downregulation of cellular lipid catabolism. Co-treatments with MTI-31 and etomoxir enhanced the suppression of cyclin D1, c-Myc and cell growth in HER2+/PIK3CAmut tumors. These new mechanistic findings provide a rationale for targeting mTORC1 and mTORC2 in HER2+/PIK3CAmut breast cancer. PMID- 27563816 TI - Gene status and clinicopathologic characteristics of lung adenocarcinomas with mediastinal lymph node metastasis. AB - Lung cancer with mediastinal lymph node metastasis is more likely to develop recurrence and metastasis after complete resection and targeted therapy is a promising treatment strategy. We performed amplification refractory mutation system (ARMS) fluorescence quantitative PCR to detect the gene status of EGFR, ALK, ROS1 and RET in resected samples from 280 patients who were confirmed to have primary lung adenocarcinomas with N1-N2 lymph node metastasis. Of the 280 patients enrolled, the frequency of EGFR mutations, ALK fusions, ROS1 fusions, RET fusions and no mutations was 42.9%, 10.7%, 1.8%, 3.6% and 42.9%, respectively. Five patients exhibited the coexistence of the EGFR and ALK alterations. ALK, ROS1 and RET fusions were mutually exclusive. The frequency of EGFR mutation was significantly lower among patients with poor differentiation, while the rates of ALK and ROS1 fusions were the opposite. RET fusions also tended to be more prevalent in poorly differentiated patients. EGFR and ALK double positive tumors were characterized by significantly smaller size compared with those had single gene alteration. Our study comprehensively analyzed the distinct and common clinicopathologic characteristics according to genotypes of the cohort, which should help in categorizing patients for efficient screening. PMID- 27563815 TI - KIF-2C expression is correlated with poor prognosis of operable esophageal squamous cell carcinoma male patients. AB - To determine the prognostic significance of Kinesin family member 2C (KIF-2C) expression in patients with operable esophageal squamous cell carcinoma (ESCC), we conducted an immunohistochemical analysis of KIF-2C expression in 415 surgically resected primary tumor tissues and 40 adjacent non-cancerous tissues from patients with operable ESCC. The median duration of postoperative follow-up was 76.0 months. Higher KIF-2C expression was associated with significantly increased risks of higher pathologic tumor (pT) status (P=0.038) and poorer tumor differentiation (P=0.022). For the entire cohort, KIF-2C expression was not an independent factor significantly associated with overall survival (OS) (P=0.097) or disease-free survival (DFS) (P=0.152). In female patients, KIF-2C expression had no effect on OS (P=0.880) and DFS (P=0.864). However, OS (hazard ratio (HR)=1.480, P=0.013) and DFS (HR=1.418, P=0.024) were worse for male patients with high KIF-2C expression compared with male patients with low KIF-2C expression. Moreover, the OS and DFS of male patients with high KIF-2C expression were also significantly shorter compared with female patients with low KIF-2C expression (P=0.022, P=0.029) and female patients with high KIF-2C expression (P=0.014, P=0.018). Based on these findings, KIF-2C expression in tumor tissues promises to serve as an independent prognostic marker for male, but not female, patients with operable ESCC. Prognosis was worse for male patients with high KIF 2C expression compared with patients with the same pathologic tumor-node metastasis (pTNM) stage. PMID- 27563817 TI - EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells. AB - Cancer cells acquire essential characteristics for metastatic dissemination through the process of epithelial-to-mesenchymal transition (EMT), which is regulated by gene expression and chromatin remodeling changes. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3) to repress gene transcription. Here we report the functional roles of EZH2-catalyzed H3K27me3 during EMT in ovarian cancer (OC) cells. TGF-beta-induced EMT in SKOV3 OC cells was associated with decreased levels of EZH2 and H3K27me3 (P<0.05). These effects were delayed (~72 h relative to EMT initiation) and coincided with increased (>15-fold) expression of EMT-associated transcription factors ZEB2 and SNAI2. EZH2 knockdown (using siRNA) or enzymatic inhibition (by GSK126) induced EMT-like changes in OC cells. The EMT regulator ZEB2 was upregulated in cells treated with either approach. Furthermore, TGF-beta enhanced expression of ZEB2 in EZH2 siRNA- or GSK126-treated cells (P<0.01), suggesting that H3K27me3 plays a role in TGF-beta-stimulated ZEB2 induction. Chromatin immunoprecipitation assays confirmed that TGF-beta treatment decreased binding of EZH2 and H3K27me3 to the ZEB2 promoter (P<0.05). In all, these results demonstrate that EZH2, by repressing ZEB2, is required for the maintenance of an epithelial phenotype in OC cells. PMID- 27563818 TI - Cadherin-6 type 2, K-cadherin (CDH6) is regulated by mutant p53 in the fallopian tube but is not expressed in the ovarian surface. AB - High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy and may arise in either the fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). A mutation in p53 is reported in 96% of HGSOC, most frequently at R273 and R248. The goal of this study was to identify specific gene targets in the FTE that are altered by mutant p53, but not in the OSE. Gene analysis revealed that both R273 and R248 mutant p53 reduces CDH6 expression in the oviduct, but CDH6 was not detected in murine OSE cells. p53R273H induced SLUG and FOXM1 while p53R248W did not induce SLUG and only modestly increased FOXM1, which correlated with less migration as compared to p53R273H. An oviduct specific PAX8Cre/+/p53R270H/+ mouse model was created and confirmed that in vivo mutant p53 repressed CDH6 but was not sufficient to stabilize p53 expression alone. Overexpression of mutant p53 in the p53 null OVCAR5 cells decreased CDH6 levels indicating this was a gain-of-function. SLUG knockdown in murine oviductal cells with p53R273H restored CDH6 repression and a ChIP analysis revealed direct binding of mutant p53 on the CDH6 promoter. NSC59984, a small molecule that degrades mutant p53R273H, rescued CDH6 expression. In summary, CDH6 is expressed in the oviduct, but not the ovary, and is repressed by mutant p53. CDH6 expression with further validations may aide in establishing markers that inform upon the cell of origin of high grade serous tumors. PMID- 27563819 TI - Cytokines can counteract the inhibitory effect of MEK-i on NK-cell function. AB - Oncogene-targeted therapies based on mutated BRAF- and/or MEK-specific inhibitors have been developed for melanoma treatment. Although these drugs induce tumor regression in a high percentage of patients, clinical responses are frequently limited in time and tumors often recur. Recent studies suggested that the combination of BRAF/MEK inhibition with immunotherapy could represent a promising strategy for the cure of melanoma. NK cells are suitable effectors for tumor immunotherapy. Here we show that PLX4032 (a mutant BRAFV600 inhibitor) had no effect on the functional properties of NK cells cultured in the presence of IL-2 or IL-15. In contrast, PD0325901 (a MEK inhibitor) induced the down-regulation of the main activating NK receptors and inhibited NK cell function. Importantly, PD0325901 did not affect the anti-tumor activity of NK cells that had been exposed to a combination of IL-15 and IL-18. In addition, both PLX4032 and PD0325901 did not exert any inhibitory effect on in vitro IL-2 or IL-15 pre activated NK cells.Our data may provide a rationale for future clinical protocols that combine IL-15/IL-18 cytokine administration with MEK inhibitors. In addition, they suggest that oncogene-targeting drugs are compatible with NK-based adoptive therapy. PMID- 27563820 TI - ATF6alpha regulates morphological changes associated with senescence in human fibroblasts. AB - Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated beta galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated shape changes and organelle alterations. However, the underlying molecular mechanisms responsible for these last changes remain still uncharacterized. Herein, we have identified the Unfolded Protein Response (UPR) as a player controlling some morphological aspects of the senescent phenotype. We show that senescent fibroblasts exhibit ER expansion and mild UPR activation, but conserve an ER stress adaptive capacity similar to that of exponentially growing cells. By genetically invalidating the three UPR sensors in senescent fibroblasts, we demonstrated that ATF6alpha signaling dictates senescence-associated cell shape modifications. We also show that ER expansion and increased secretion of the pro-inflammatory mediator IL6 were partly reversed by silencing ATF6alpha in senescent cells. Moreover, ATF6alpha drives the increase of senescence associated-beta-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6alpha in the establishment of morphological features of senescence in normal human primary fibroblasts. PMID- 27563821 TI - AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma. AB - AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains.The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p < 0.05). Vaccination against MAGEB2 induced higher frequency of MAGEB2-specific CTL and exerted higher protective effect against melanoma development in mice bearing the CC AIRE genotype than in those bearing the TT one (p < 0.05). These findings show that allelic variants of one AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma. PMID- 27563822 TI - The BCR-ABL/NF-kappaB signal transduction network: a long lasting relationship in Philadelphia positive Leukemias. AB - The Nuclear Factor-kappa B (NF-kappaB) family of transcription factors plays a key role in cancer pathogenesis due to the ability to promote cellular proliferation and survival, to induce resistance to chemotherapy and to mediate invasion and metastasis. NF-kappaB is recruited through different mechanisms involving either canonical (RelA/p50) or non-canonical pathways (RelB/p50 or RelB/p52), which transduce the signals originated from growth-factors, cytokines, oncogenic stress and DNA damage, bacterial and viral products or other stimuli. The pharmacological inhibition of the NF-kappaB pathway has clearly been associated with significant clinical activity in different cancers. Almost 20 years ago, NF-kappaB was described as an essential modulator of BCR-ABL signaling in Chronic Myeloid Leukemia and Philadelphia-positive Acute Lymphoblastic Leukemia. This review summarizes the role of NF-kappaB in BCR-ABL-mediated leukemogenesis and provides new insights on the long lasting BCR-ABL/NF-kappaB connection. PMID- 27563823 TI - Fusion between cancer cells and macrophages occurs in a murine model of spontaneous neu+ breast cancer without increasing its metastatic potential. AB - Cell fusion between neoplastic and normal cells has been suggested to play a role in the acquisition of a malignant phenotype. Several studies have pointed to the macrophage as the normal partner in this fusion, suggesting that the fused cells could acquire new invasive properties and become able to disseminate to distant organs. However, this conclusion is mainly based on studies with transplantable cell lines. We tested the occurrence of cell fusion in the MMTV-neu model of mouse mammary carcinoma. In the first approach, we generated aggregation chimeras between GFP/neu and RFP/neu embryos. Tumor cells would display both fluorescent proteins only if cell fusion with normal cells occurred. In addition, if cell fusion conferred a growth/dissemination advantage, cells with both markers should be detectable in lung metastases at increased frequency. We confirmed that fused cells are present at low but consistent levels in primary neoplasms and that the macrophage is the normal partner in the fusion events. Similar results were obtained using a second approach in which bone marrow from mice carrying the Cre transgene was transplanted into MMTV-neu/LoxP-tdTomato transgenic animals, in which the Tomato gene is activated only in the presence of CRE recombinase. However, no fused cells were detected in lung metastases in either model. We conclude that fusion between macrophages and tumor cells does not confer a selective advantage in our spontaneous model of breast cancer, although these data do not rule out a possible role in models in which an inflammation environment is prominent. PMID- 27563825 TI - Two subtypes of colorectal tumor with distinct molecular features in familial adenomatous polyposis. AB - While sporadic colorectal cancer (CRC) is classified into several molecular subtypes, stratification of familial colorectal tumors is yet to be well investigated. We previously established two groups of methylation markers through genome-wide DNA methylation analysis, which classified sporadic CRC and adenoma into three distinct subgroups: high-, intermediate-, and low-methylation epigenotypes. Here, we investigated familial adenomatous polyposis (FAP), through quantitative methylation analysis of 127 samples (16 cancers, 96 adenomas, and 15 benign mucosa from 14 patients with FAP) using six Group-1 and 14 Group-2 methylation markers, APC, BRAF, and KRAS mutation analysis, and CTNNB1 and TP53 immunohistochemical analysis. All the 14 patients presented with APC germline mutation. Three were from the same family and presented the same APC mutation. FAP tumors lacked BRAF-mutation(+) high-methylation epigenotype and were classified into two methylation epigenotypes. While 24 of 112 tumor samples showed intermediate-methylation epigenotype significantly correlating with KRAS mutation(+) (P=3*10-4), 88 tumor samples showed low-methylation epigenotype correlating with the absence of KRAS- and BRAF-mutations. Similar to sporadic CRC, CTNNB1 was frequently activated at the adenoma stage, and TP53 mutation occurred during cancer development from adenoma. Whereas some patients showed a single epigenotype in all tumors throughout the colon, tumors with two distinct epigenotypes developed within a family with the same APC mutation or even within one patient. Methylation accumulation significantly correlated with proximal location and older age. These results indicate that there are at least two distinct molecular subtypes of FAP tumors, resembling sporadic CRC and independent from the APC germline mutation status. PMID- 27563826 TI - A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct. AB - MASTL (microtubule-associated serine/threonine kinase-like), more commonly known as Greatwall (GWL), has been proposed as a novel cancer therapy target. GWL plays a crucial role in mitotic progression, via its known substrates ENSA/ARPP19, which when phosphorylated inactivate PP2A/B55 phosphatase. When over-expressed in breast cancer, GWL induces oncogenic properties such as transformation and invasiveness. Conversely, down-regulation of GWL selectively sensitises tumour cells to chemotherapy. Here we describe the first structure of the GWL minimal kinase domain and development of a small-molecule inhibitor GKI-1 (Greatwall Kinase Inhibitor-1). In vitro, GKI-1 inhibits full-length human GWL, and shows cellular efficacy. Treatment of HeLa cells with GKI-1 reduces ENSA/ARPP19 phosphorylation levels, such that they are comparable to those obtained by siRNA depletion of GWL; resulting in a decrease in mitotic events, mitotic arrest/cell death and cytokinesis failure. Furthermore, GKI-1 will be a useful starting point for the development of more potent and selective GWL inhibitors. PMID- 27563824 TI - Pediatric Hodgkin lymphoma: biomarkers, drugs, and clinical trials for translational science and medicine. AB - Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-kappaB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF kappaB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging. Targeted HL therapy with the antibody-drug conjugate Brentuximab vedotin (Bv) has proven to be superior to conventional salvage chemotherapy and clinical trials are being conducted to incorporate Bv into frontline therapy that substitutes Bv for alkylating agents to minimize secondary malignancies. The appearance of secondary malignancies has been a concern in pediatric HL, as these patients are at highest risk among all childhood cancer survivors. The risk of developing secondary leukemia following childhood HL treatment is 10.4 to 174.8 times greater than the risk in the general pediatric population and the prognosis is significantly poorer than the other hematological malignancies with a mortality rate of nearly 100%. Therefore, identifying clinically valuable biomarkers is of utmost importance to stratify and select patients who may or may not need intensive regimens to maintain optimal balance between maximal survival rates and averting late effects. Here we discuss epidemiology, risk factors, staging, molecular and genetic prognostic biomarkers, treatment for low and high-risk patients, and the late occurrence of secondary malignancies in pediatric HL. PMID- 27563827 TI - Integrin beta1, myosin light chain kinase and myosin IIA are required for activation of PI3K-AKT signaling following MEK inhibition in metastatic triple negative breast cancer. AB - The effectiveness of targeted therapies against the Ras-ERK signaling pathway are limited due to adaptive resistance of tumor cells. Inhibition of the Ras-ERK pathway can result in activation of the PI3K-AKT pathway, thereby diminishing the therapeutic effects of targeting ERK signaling. Here we investigated the crosstalk between the Ras-ERK and PI3K-AKT pathways in MDA-MB-231 breast cancer cell lines that have a preference to metastasize to lung (LM2), brain (BrM2) or bone (BoM2). Inhibition of the Ras-ERK pathway reduced motility in both parental and BoM2 cells. In contrast, inhibition of the Ras-ERK pathway in BrM2 and LM2 cells resulted in activation of PI3K-AKT signaling that was responsible for continued cell motility. Analysis of the cross talk between Ras-ERK and PI3K-AKT signaling pathways revealed integrin beta1, myosin light chain kinase (MLCK) and myosin IIA are required for the activation of PI3K-AKT following inhibition of the Ras-ERK pathway. Furthermore, feedback activation of the PI3K-AKT pathway following MEK suppression was independent of the epidermal growth factor receptor. Thus, integrin beta1, MLCK, and myosin IIA are factors in the development of resistance to MEK inhibitors. These proteins could provide an opportunity to develop markers and therapeutic targets in a subgroup of triple negative breast cancer (TNBC) that exhibit resistance against MEK inhibition. PMID- 27563828 TI - IPMK and beta-catenin mediate PLC-beta1-dependent signaling in myogenic differentiation. AB - In previous studies, we have reported that phospholipase C (PLC)-beta1 plays a crucial role in myogenic differentiation and we determined the importance of its catalytic activity for the initiation of this process. Here we define the effectors that take part to its signaling pathway. We show that the Inositol Polyphosphate Multikinase (IPMK) is able to promote myogenic differentiation since its overexpression determines the up-regulation of several myogenic markers. Moreover, we demonstrate that IPMK activates the same cyclin D3 promoter region targeted by PLC-beta1 and that IPMK-induced promoter activation relies upon c-jun binding to the promoter, as we have shown previously for PLC-beta1. Furthermore, our data shows that IPMK overexpression causes an increase in beta catenin translocation and accumulation to the nuclei of differentiating myoblasts resulting in higher MyoD activation. Finally, we describe that PLC-beta1 overexpression determines too an increase in beta-catenin translocation and that PLC-beta1, IPMK and beta-catenin are mediators of the same signaling pathway since their overexpression results in cyclin D3 and myosin heavy chain (MYH) induction. PMID- 27563829 TI - Variations of Leaf Cuticular Waxes Among C3 and C4 Gramineae Herbs. AB - Modern C4 plants are commonly distributed in hot and dry environments whereas C3 plants predominate in cool and shade areas. At the outmost of plant surface, the deposition and chemical composition of cuticular waxes vary under different environmental conditions. However, whether such variation of cuticular wax is related to the distribution of C3 and C4 under different environmental conditions is still not clear. In this study, leaves of six C3 Gramineae herbs distributed in spring, Roegneria kamoji, Polypogon fugax, Poa annua, Avena fatua, Alopecurus aequalis, and Oplismenus undulatifolius, and four C4 and one C3 Gramineae herbs distributed in summer, Digitaria sanguinalis, Eleusine indica, Setaria viridis, S. plicata, and O. undulatifolius, were sampled and analyzed for cuticular wax. Plates were the main epicuticular wax morphology in both C3 and C4 plants except S. plicata. The plates melted in C4 plants but not in C3 plants. The total cuticular wax amounts in C4 plants were significantly lower than those in C3 plants, except for O. undulatifolius. Primary alcohols were the most abundant compounds in C3 plants, whereas n-alkanes were relatively the most abundant compounds in C4 plants. C29 was the most abundant n-alkane in C3 plants except for O. undulatifolius, whereas the most abundant n-alkane was C31 or C33 in C4 plants. The average chain length (ACL) of n-alkanes was higher in C4 than in C3 plants, whereas the ACL of n-alkanoic acids was higher in C3 than C4 plants. The cluster analysis based on the distribution of n-alkanes clearly distinguished C3 and C4 plants into two groups, except for O. undulatifolius which was grouped with C4 plants. These results suggest that the variations of cuticular waxes among C3 and C4 Gramineae herbs are related to the distribution of C3 and C4 plants under different environmental conditions. PMID- 27563830 TI - Long-Term Clinical and Histological Effects of a Bipolar Fractional Radiofrequency System in the Treatment of Facial Atrophic Acne Scars and Acne Vulgaris in Japanese Patients: A Series of Eight Cases. AB - OBJECTIVE: This retrospective case series was designed to compare the long-term safety and efficacy of bipolar fractional radiofrequency (FRF) therapy as a treatment for atrophic acne scars (ASs) and acne vulgaris. BACKGROUND DATA: Few clinical and histological studies have examined the long-term utility of bipolar FRF therapy as a treatment for ASs and acne in people with darker skin. MATERIALS AND METHODS: Eight Japanese patients with ASs and mild-to-severe acne on both cheeks were treated with a bipolar FRF system (eMatrix; Syneron). Five treatment sessions with the same settings (coverage rate: 10%; peak energy: 62 mJ/pin; two passes) were carried out at 1-month intervals, and the patients were followed up for at least 1 year after the final treatment. Assessments of ASs and acne severity were performed and samples were removed for histological examination. RESULTS: We demonstrated that mild ASs responded better than moderate and severe ASs, and at least 50% improvement in scar severity was seen in 50% of patients after the final treatment. Six patients remained disease free at 1.5 years without the use of any additional therapies. The biopsy specimens showed a marked improvement characterized by a decrease in dermal pilosebaceous units and perivascular inflammatory cell infiltrates with an increase in elastin content and collagen deposition in the upper dermis. CONCLUSIONS: Bipolar FRF treatment showed long-term effectiveness against mild ASs and acne in Asian patients and had minimal side effects. PMID- 27563831 TI - Efficacy of Tailored Exercise Therapy on Physical Functioning in Patients With Knee Osteoarthritis and Comorbidity: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities. METHODS: In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index >=30 kg/m2 ), with severity score >=2 on the Cumulative Illness Rating Scale. The intervention group received a 20-week, individualized, comorbidity-adapted exercise program consisting of aerobic and strength training and training of daily activities. The control group received their current medical care for knee OA and were placed on a waiting list for exercise therapy. Primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index, subscale physical functioning (WOMAC-pf), and the 6-minute walk test (6MWT). Measurements were performed at baseline, after 20 weeks (directly posttreatment), and at 3 months posttreatment. RESULTS: Statistically significant physical functioning differences over time were found between the intervention and control group (WOMAC: B = -7.43 [95% confidence interval (95% CI) -9.99, -4.87], P < 0.001; and 6MWT: B = 34.16 [95% CI 17.68, 50.64], P < 0.001) in favor of the intervention group. At 3 months followup, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention. CONCLUSION: This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with knee OA and severe comorbidities. PMID- 27563832 TI - Survival kinetics of Mycobacterium bovis during manufacture and ripening of raw milk Cheddar and Caerphilly cheese produced on a laboratory-scale. AB - AIMS: Persistence of Mycobacterium bovis was investigated in UK raw milk cheeses. METHODS AND RESULTS: Replicating traditional cheese production methods under stringent CL3 containment conditions, Cheddar and Caerphilly cheeses were produced with Myco. bovis inoculated raw milk. High-inoculum investigations used three Myco. bovis genotypes; later low-inoculum investigations used only Myco. bovis AF2122/97. High-inoculum Cheddar (n = 9) and Caerphilly (n = 9) were matured for a minimum of 12 and 4 months respectively; maturation of low-inoculum Cheddar (n = 3) and Caerphilly (n = 3) was up to 11 weeks. Survival of Myco. bovis was monitored by enumeration at different points throughout cheese manufacture and ripening. D values were calculated as follows: 57 and 59 days in high-inoculum Cheddar and Caerphilly, respectively, and 41 and 24 days in low inoculum Cheddar and Caerphilly respectively. CONCLUSIONS: Mycobacterium bovis is concentrated in cheese curd and a proportion lost with the whey. Reduction in viability during manufacturing is limited, while significant Myco. bovis inactivation occurs during maturation. Inactivation was improved, during Caerphilly ripening, when acid development was enhanced by increasing the proportion of starter culture. SIGNIFICANCE AND IMPACT OF THE STUDY: Mycobacterium bovis inactivation data obtained could be used to inform assessment of the risk posed to consumers by raw milk dairy products. PMID- 27563833 TI - Focused Library Approach to Discover Discrete Dipeptide Bolaamphiphiles for siRNA Delivery. AB - In this study, we report a new dipeptide functionalization strategy for developing new dendritic bolaamphiphile vectors for efficient siRNA transfection. A focused library of dipeptides was constructed using four amino acids: l arginine, l-histidine, l-lysine, and l-tryptophan. The dipeptides were coupled to two dendritic bolaamphiphile scaffolds that we developed previously, allowing us to quickly access a focused library of discrete vectors with multivalent dendritic dipeptide functionalities. The resulting discrete bolaamphiphiles were screened for siRNA delivery in vitro in HEK-293 and HeLa cells. Bolaamphiphiles functionalized with dipeptides containing Lys or Arg and either His or Trp were the most effective for in vitro siRNA delivery. Necessary cationic charge to ensure efficient siRNA binding are provided by Arg and Lys residues, whereas endosomal escape is provided through pH responsive buffering of His or membrane interactions of Trp. The most effective vectors (F10 HR/RH) exhibited greater than 75% gene silencing in multiple cell lines and exhibited serum stability. PMID- 27563834 TI - Effects of botulinum toxin A injections in spinal cord injury patients with detrusor overactivity and detrusor sphincter dyssynergia. AB - OBJECTIVE: To evaluate the safety and effect of botulinum toxin A injection in the detrusor and external urethral sphincter in male patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. METHODS: A multicentre trial was conducted from June 2012 to August 2015. A total of 65 spinal cord injury patients with DO and DESD participated in the study. Of these, 59 received 200 U botulinum toxin Aintradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD, VDO-DESD, maximum urethral closure pressure, duration of first DO and DESD, Incontinence Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness. Adverse events were recorded. RESULTS: All patients experienced a significant mean reduction in PdetmaxDO -DESD (46.60%), maximum urethral closure pressure (29.61%), duration of first DO and DESD (42.93%) and a significant mean increase in VDO-DESD (38.11%) 12-weeks post injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness were found in all patients at 2 weeks and were sustained at 8 weeks and 16 weeks. CONCLUSION: Botulinum toxin A injection in the detrusor and external urethral sphincter is an effective treatment to protect the upper urinary tract and improve quality of life for patients with DO and DESD secondary to spinal cord injury. PMID- 27563835 TI - Combined Effect of Body Mass Index and Renal Function on Long-Term Clinical Outcomes in Elderly Adults After Percutaneous Coronary Intervention. PMID- 27563836 TI - Composite metric R2 - R1rho (1/T2 - 1/T1rho ) as a potential MR imaging biomarker associated with changes in pain after ACL reconstruction: A six-month follow-up. AB - This study looked to investigate a new quantitative metric, R2 - R1rho (1/T2 - 1/T1rho ), using magnetic resonance (MR) images and voxel-based relaxometry (VBR) for detecting early cartilage degeneration and explore the association with patient-reported outcomes measures (PROMs) in patients 6 months after ACL reconstruction. Sixty-four patients from three sites were bilaterally scanned on a 3T MR with a combined T1rho /T2 protocol to calculate R1rho (1/T1rho ) and R2 (1/T2 ) values at baseline and 6 months after reconstructive surgery. Non-rigid registration was applied to align images onto a template, allowing VBR to determine VBR rate differences and explore cross-sectional and longitudinal differences between injured and uninjured knees, generating Statistical Parametric Maps (SPMs). Baseline R2 - R1rho differences were further correlated with change in PROMs from the Knee Injury and Osteoarthritis Outcome Score (KOOS) from baseline to 6 months. Cross-sectional results demonstrated low relaxation rate differences in the injured patella (baseline: 21%, p = 0.01; 6-months: 18%, p = 0.02), lateral tibia (baseline: 25%, p = 0.01; 6-months: 24%, p = 0.01), and weight-bearing regions of the tibia and femur. The uninjured patella showed significant longitudinal changes (17%, p = 0.02). R2 - R1rho differences showed significant correlations with KOOS PROMs, particularly in the lateral tibia, patella, and trochlea. R2 - R1rho difference VBR analyses provide new and highly sensitive parameters for assessing early cartilage degeneration in patients after ACL injury by integrating findings from both T1rho and T2 , commonly used relaxation time parameters, into a single metric. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:718-729, 2017. PMID- 27563837 TI - Single dose and repeated administrations of liraglutide alter energy metabolism in the brains of young and adult rats. AB - Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue that was recently approved to treat obesity in some countries. Considering that liraglutide effects on brain energy metabolism are little known, we evaluated the effects of liraglutide on the energy metabolism. Animals received a single or daily injection of saline or liraglutide during 7 days (25, 50, 100, or 300 MUg/kg i.p.). Twenty-four hours after the single or last injection, the rats were euthanized and the hypothalamus, prefrontal cortex, cerebellum, hippocampus, striatum, and posterior cortex were isolated. Our results demonstrated that a single dose of liraglutide in young rats increased the activity of complexes and inhibited creatine kinase activity. Repeated administrations of liraglutide in young rats reduced the activity of complexes and activated creatine kinase activity. In adult rats, a single dose of liraglutide reduced the activity of complex I and creatine kinase and increased the activity of complexes II and IV. Repeated administrations of liraglutide in adult rats increased the activity of complexes I and IV and reduced the activity of complex II and creatine kinase. We concluded that liraglutide may interfere in energy metabolism, because analysis of different times of administrations, concentrations, and level of brain development leads to divergent results. PMID- 27563838 TI - Investigational glucagon-like peptide-1 agonists for the treatment of obesity. AB - INTRODUCTION: Obesity is a worldwide problem predisposing to type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, cancer and other comorbidities. Lifestyle modification is the first line intervention but adjunctive pharmacotherapy is often required. The GLP-1 receptor agonists (GLP 1RAs) were developed primarily for T2DM and they also reduce body weight. Liraglutide was approved for the treatment of obesity and other GLP-1RAs are likely to be suitable for this indication. AREAS COVERED: This review describes the GLP-1RAs that have been approved for the treatment of T2DM as potential candidates for the treatment of obesity and the new agents currently under development which may have advantages in patient adherence. EXPERT OPINION: The GLP-1RAs offer a welcome addition to obesity pharmacotherapy. They appear to be free of serious adverse effects although uncertainty remains about possible risks of pancreatitis and neoplasms. However, they have frequent gastrointestinal side effects, particularly nausea, which limits their tolerability. Cardiovascular outcome studies in T2DM support their use and this is likely to increase in both T2DM and obesity. Other GLP-1RAs which can be given by subcutaneous injection once weekly or less frequently or by oral administration would have advantages especially if nausea is less frequent than with liraglutide. PMID- 27563839 TI - Epidemiology of cutaneous melanoma in Sweden-Stage-specific survival and rate of recurrence. AB - Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care even more urgent. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3,554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted 5-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with 5-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stages I and IV patients, respectively. In addition to stage, male gender, and age, circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments. PMID- 27563840 TI - Staging liver fibrosis in chronic hepatitis B with T1 relaxation time index on gadoxetic acid-enhanced MRI: Comparison with aspartate aminotransferase-to platelet ratio index and FIB-4. AB - PURPOSE: To assess the accuracy of the T1 relaxation time index on gadoxetic acid enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B (CHB), in comparison and combination with the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4). MATERIALS AND METHODS: A retrospective study of gadoxetic acid-enhanced T1 mapping and serum biochemical tests was performed on 126 CHB patients who underwent gadoxetic acid-enhanced 1.5T MRI, and the histological score used as the gold standard. The reduction rate of T1 relaxation time before and 20 minutes after gadoxetic acid injection (DeltaT1 , DeltaR1%), the contrast uptake rate (KHep ), APRI, and FIB-4 were calculated. The diagnostic efficacy of DeltaT1 , DeltaR1%, KHep , APRI, and FIB-4 for predicting stage 2 or greater (>=S2), stage 3 or greater (>=S3), and stage 4 (S4) was compared. RESULTS: DeltaT1 (r = -0.513, P < 0.001), DeltaR1% (r = -0.626, P < 0.001), KHep (r = -0.527, P < 0.001), APRI (r = 0.519, P < 0.001), and FIB-4 (r = 0.476, P < 0.001) correlated significantly with fibrosis stages. Areas under the curves (AUCs) of DeltaR1% for detecting >=S2, >=S3, and S4 were 0.849, 0.827, and 0.809, which were greater than that of APRI (0.763, 0.745, 0.787) and FIB-4 (0.727, 0.738, 0.772), but significant difference was found only in discriminating >=S2 between DeltaR1% and FIB-4 (P = 0.027). The combination of all five indices performed best, with AUC, sensitivity, and specificity of 0.860, 87.21%, and 72.50% for diagnosing >=S2, 0.878, 82.81%, and 85.48% for >=S3, and 0.867, 80.00%, and 83.95% for S4. CONCLUSION: The gadoxetic acid-enhanced T1 relaxation time index appears to be superior to APRI and FIB-4 for predicting hepatic fibrosis. The combined use of gadoxetic acid-enhanced T1 mapping, APRI, and FIB-4 may be more reliable for staging liver fibrosis in CHB. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:1186-1194. PMID- 27563841 TI - Synthesis and glycosidase inhibition evaluation of (3S,4S)-3-((R)-1,2 dihydroxyethyl)pyrrolidine-3,4-diol. AB - A new azasugar (3S,4S)-3-((R)-1,2-dihydroxyethyl)pyrrolidine-3,4-diol (1) was obtained from commercially available d-glucose using one-pot reductive cyclization as a key step. The target product, i.e., the iminosugar isomer, was obtained in 10 steps and 24.3% overall yield. Only three column chromatography purifications were needed in this synthesis. The biological activity of the target molecule as glycosidase inhibitor was studied, but the inhibitory activity against four glycosidases was not good (IC50 > 100 MUM). PMID- 27563842 TI - Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging-A prospective trial. AB - BACKGROUND: Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single-photon emission computed tomography/computed tomography (SPECT-CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET-CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT-CT with PET-CT for the identification of nodal metastases in pediatric and AYA patients. METHODS: Twenty eight pediatric and AYA sarcoma patients underwent SLNB with SPECT-CT. The histological findings of the excised lymph nodes were then correlated with preoperative PET-CT imaging. RESULTS: A median of 2.4 sentinel nodes were sampled per patient. No wound infections or chronic lymphedema occurred. SLNB identified tumors in 7 of the 28 patients (25%), including 3 patients who had normal PET-CT imaging of the nodal basin. In contrast, PET-CT demonstrated hypermetabolic regional nodes in 14 patients, and this resulted in a positive predictive value of only 29%. The sensitivity and specificity of PET-CT for detecting histologically confirmed nodal metastases were only 57% and 52%, respectively. CONCLUSIONS: SLNB can safely guide the rational selection of nodes for biopsy in pediatric and AYA sarcoma patients and can identify therapy-changing nodal disease not appreciated with PET-CT. Cancer 2017;155-160. (c) 2016 American Cancer Society. PMID- 27563843 TI - Knee Extensor Strength and Risk of Structural, Symptomatic, and Functional Decline in Knee Osteoarthritis: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: To perform a systematic review and meta-analysis on the association between knee extensor strength and the risk of structural, symptomatic, or functional deterioration in individuals with or at risk of knee osteoarthritis (KOA). METHODS: We systematically identified and methodologically appraised all longitudinal studies (>=1-year followup) reporting an association between knee extensor strength and structural (tibiofemoral, patellofemoral), symptomatic (self-reported, knee replacement), or functional (subjective, objective) decline in individuals with or at risk of radiographic or symptomatic KOA. Results were pooled for each of the above associations using meta-analysis, or if necessary, summarized according to a best-evidence synthesis. RESULTS: Fifteen studies were included, evaluating >8,000 participants (51% female), with a followup time between 1.5 and 8 years. Meta-analysis revealed that lower knee extensor strength was associated with an increased risk of symptomatic (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain: odds ratio [OR] 1.35, 95% confidence interval [95% CI] 1.10-1.67) and functional decline (WOMAC function: OR 1.38, 95% CI 1.00-1.89, and chair-stand task: OR 1.03, 95% CI 1.03 1.04), but not increased risk of radiographic tibiofemoral joint space narrowing (JSN) (OR 1.15, 95% CI 0.84-1.56). No trend in risk was observed for KOA status (present versus absent). Best-evidence synthesis showed inconclusive evidence for lower knee extensor strength being associated with increased risk of patellofemoral deterioration. CONCLUSION: Meta-analysis showed that lower knee extensor strength is associated with an increased risk of symptomatic and functional deterioration, but not tibiofemoral JSN. The risk of patellofemoral deterioration in the presence of knee extensor strength deficits is inconclusive. PMID- 27563845 TI - Biotechnology and Bioengineering: Volume 113, Number 10, October 2016. PMID- 27563844 TI - Co-delivery of cell-wall-forming enzymes in the same vesicle for coordinated fungal cell wall formation. AB - Fungal cells are surrounded by an extracellular cell wall. This complex matrix of proteins and polysaccharides protects against adverse stresses and determines the shape of fungal cells. The polysaccharides of the fungal wall include 1,3-beta glucan and chitin, which are synthesized by membrane-bound synthases at the growing cell tip. A hallmark of filamentous fungi is the class V chitin synthase, which carries a myosin-motor domain. In the corn smut fungus Ustilago maydis, the myosin-chitin synthase Mcs1 moves to the plasma membrane in secretory vesicles, being delivered by kinesin-1 and myosin-5. The myosin domain of Mcs1 enhances polar secretion by tethering vesicles at the site of exocytosis. It remains elusive, however, how other cell-wall-forming enzymes are delivered and how their activity is coordinated post secretion. Here, we show that the U. maydis class VII chitin synthase and 1,3-beta-glucan synthase travel in Mcs1-containing vesicles, and that their apical secretion depends on Mcs1. Once in the plasma membrane, anchorage requires enzyme activity, which suggests co-synthesis of chitin and 1,3-beta-glucan polysaccharides at sites of exocytosis. Thus, delivery of cell-wall-forming enzymes in Mcs1 vesicles ensures local foci of fungal cell wall formation. PMID- 27563846 TI - Effective utilization of green algae for production of antioxidants. PMID- 27563847 TI - Bio-separation optimization via microscale filtration and DOE. PMID- 27563848 TI - A general post-translational tool for metabolic engineering. PMID- 27563849 TI - 13 organ human surrogate for drug development. PMID- 27563850 TI - A new paradigm for producing astaxanthin from the unicellular green alga Haematococcus pluvialis. AB - The unicellular green alga Haematococcus pluvialis has been exploited as a cell factory to produce the high-value antioxidant astaxanthin for over two decades, due to its superior ability to synthesize astaxanthin under adverse culture conditions. However, slow vegetative growth under favorable culture conditions and cell deterioration or death under stress conditions (e.g., high light, nitrogen starvation) has limited the astaxanthin production. In this study, a new paradigm that integrated heterotrophic cultivation, acclimation of heterotrophically grown cells to specific light/nutrient regimes, followed by induction of astaxanthin accumulation under photoautotrophic conditions was developed. First, the environmental conditions such as pH, carbon source, nitrogen regime, and light intensity, were optimized to induce astaxanthin accumulation in the dark-grown cells. Although moderate astaxanthin content (e.g., 1% of dry weight) and astaxanthin productivity (2.5 mg L(-1) day(-1) ) were obtained under the optimized conditions, a considerable number of cells died off when subjected to stress for astaxanthin induction. To minimize the susceptibility of dark-grown cells to light stress, the algal cells were acclimated, prior to light induction of astaxanthin biosynthesis, under moderate illumination in the presence of nitrogen. Introduction of this strategy significantly reduced the cell mortality rate under high-light and resulted in increased cellular astaxanthin content and astaxanthin productivity. The productivity of astaxanthin was further improved to 10.5 mg L(-1) day(-1) by implementation of such a strategy in a bubbling column photobioreactor. Biochemical and physiological analyses suggested that rebuilding of photosynthetic apparatus including D1 protein and PsbO, and recovery of PSII activities, are essential for acclimation of dark-grown cells under photo induction conditions. Biotechnol. Bioeng. 2016;113: 2088-2099. (c) 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID- 27563852 TI - Optimization of biomolecule separation by combining microscale filtration and design-of-experiment methods. AB - There is considerable interest in developing microscale (i.e., high-throughput) methods that enable multiple filtration experiments to be run in parallel with smaller sample amounts and thus reduce the overall required time and associated cost to run the filtration tests. Previous studies to date have focused on simply evaluating the filtration capacity, not the separation performance. In this work, the stirred-well filtration (SWF) method was used in combination with design-of experiment (DOE) methods to optimize the separation performance for three binary mixtures of bio-molecules: protein-protein, protein-polysaccharide, and protein DNA. Using the parallel based format of the SWF method, eight constant-flux ultrafiltration experiments were conducted at once to study the effects of stirring conditions, permeate flux, and/or solution conditions (pH, ionic strength). Four separate filtration tests were conducted for each combination of process variables; in total, over 100 separate tests were conducted. The sieving coefficient and selectivity results are presented to match the DOE design format and enable a greater understanding of the effects of the different process variables that were studied. The method described herein can be used to rapidly determine the optimal combination of process factors that give the best separation performance for a range of membrane-based separations applications and thus obviate the need to run a large number of traditional lab-scale tests. Biotechnol. Bioeng. 2016;113: 2131-2139. (c) 2016 Wiley Periodicals, Inc. PMID- 27563851 TI - Concentrating membrane proteins using ultrafiltration without concentrating detergents. AB - Membrane proteins (MPs) are of rapidly growing interest in the design of pharmaceutical products, novel sensors, and synthetic membranes. Ultrafiltration (UF) using commercially available centrifugal concentrators is typically employed for laboratory-scale concentration of low-yield MPs, but its use is accompanied by a concomitant increase in concentration of detergent micelles. We present a detailed analysis of the hydrodynamic processes that control detergent passage during ultrafiltration of MPs and propose methods to optimize detergent passage during protein concentration in larger-scale membrane processes. Experiments were conducted using nonionic detergents, octyl-beta-D glucoside (OG), and decyl-beta D maltoside (DM) with the bacterial water channel protein, Aquaporin Z (AqpZ) and the light driven chloride pump, halorhodopsin (HR), respectively. The observed sieving coefficient (So ), a measure of detergent passage, was evaluated in both stirred cell and centrifugal systems. So for DM and OG increased with increasing filtrate flux and decreasing shear rates in the stirred cell, that is, with increasing concentration polarization (CP). Similar effects were observed during filtration of MP-detergent (MPD) micelles. However, lower transmission was observed in the centrifugal system for both detergent and MPD systems. This is attributed to free convection-induced shear and hence reduced CP along the membrane surface during centrifugal UF. Thus to concentrate MPs without retention of detergent, design of UF systems that promote CP is required. Biotechnol. Bioeng. 2016;113: 2122-2130. (c) 2016 Wiley Periodicals, Inc. PMID- 27563854 TI - Multi-omic profiling of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production. PMID- 27563855 TI - Comparative lipid production by oleaginous yeasts in hydrolyzates of lignocellulosic biomass and process strategy for high titers. PMID- 27563853 TI - Plasmonic activation of gold nanorods for remote stimulation of calcium signaling and protein expression in HEK 293T cells. AB - Remote activation of specific cells of a heterogeneous population can provide a useful research tool for clinical and therapeutic applications. Here, we demonstrate that photostimulation of gold nanorods (AuNRs) using a tunable near infrared (NIR) laser at specific longitudinal surface plasmon resonance wavelengths can induce the selective and temporal internalization of calcium in HEK 293T cells. Biotin-PEG-Au nanorods coated with streptavidin Alexa Fluor-633 and biotinylated anti-His antibodies were used to decorate cells genetically modified with His-tagged TRPV1 temperature-sensitive ion channel and AuNRs conjugated to biotinylated RGD peptide were used to decorate integrins in unmodified cells. Plasmonic activation can be stimulated at weak laser power (0.7 4.0 W/cm(2) ) without causing cell damage. Selective activation of TRPV1 channels could be controlled by laser power between 1.0 and 1.5 W/cm(2) . Integrin targeting robustly stimulated calcium signaling due to a dense cellular distribution of nanoparticles. Such an approach represents a functional tool for combinatorial activation of cell signaling in heterogeneous cell populations. Our results suggest that it is possible to induce cell activation via NIR-induced gold nanorod heating through the selective targeting of membrane proteins in unmodified cells to produce calcium signaling and downstream expression of specific genes with significant relevance for both in vitro and therapeutic applications. Biotechnol. Bioeng. 2016;113: 2228-2240. (c) 2016 Wiley Periodicals, Inc. PMID- 27563857 TI - DNA Three Way Junction Core Decorated with Amino Acids-Like Residues-Synthesis and Characterization. AB - Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5'-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post synthetic CuACC reaction with either protected imidazolyl-, hydroxyl- or carboxyl azide. Structural impacts of 5'-C(S)-functionalization were investigated to evaluate how 3WJ flexibility/stability is affected. PMID- 27563858 TI - Plant Cell Cancer: May Natural Phenolic Compounds Prevent Onset and Development of Plant Cell Malignancy? A Literature Review. AB - Phenolic compounds (PCs) are known as a chemically diverse category of secondary and reactive metabolites which are produced in plants via the shikimate phenylpropanoid pathways. These compounds-ubiquitous in plants-are an essential part of the human diet, and are of considerable interest due to their antioxidant properties. Phenolic compounds are essential for plant functions, because they are involved in oxidative stress reactions, defensive systems, growth, and development. A large body of cellular and animal evidence carried out in recent decades has confirmed the anticancer role of PCs. Phytohormones-especially auxins and cytokinins-are key contributors to uncontrolled growth and tumor formation. Phenolic compounds can prevent plant growth by the endogenous regulation of auxin transport and enzymatic performance, resulting in the prevention of tumorigenesis. To conclude, polyphenols can reduce plant over-growth rate and the development of tumors in plant cells by regulating phytohormones. Future mechanistic studies are necessary to reveal intracellular transcription and transduction agents associated with the preventive role of phenolics versus plant pathological malignancy cascades. PMID- 27563859 TI - Elucidation of Differential Accumulation of 1-Phenylethanol in Flowers and Leaves of Tea (Camellia sinensis) Plants. AB - 1-Phenylethanol (1PE) is a major aromatic volatile in tea (Camellia sinensis) flowers, whereas it occurs in a much smaller amounts in leaves. Enzymes involved in the formation of 1PE in plants and the reason why 1PE differentially accumulates in plants is unknown. In the present study, enzymes in the last step leading from acetophenone to 1PE were isolated from tea flowers by traditional biochemical chromatography. The two types of partially purified enzymes were proposed to be responsible for formations of (R)-1PE and (S)-1PE, respectively. Tea leaves also contained such enzymes having equivalent activities with flowers. Stable isotope labeling experiments indicated that weak transformation from l phenylalanine to acetophenone in leaves mainly resulted in little occurrence of 1PE in leaves. This study provided an example that differential distribution of some metabolites in plant tissues was not only determined by enzyme(s) in the last step of metabolite formation, but also can be due to substrate availability. PMID- 27563860 TI - Three New Isoprenylated Flavonoids from the Root Bark of Morus alba. AB - Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated flavonoids: euchrenone a7 (4), sanggenon J (5), kuwanon E (6), and kuwanon S (7). All compounds were isolated by repeated silica gel (SiO2), octadecyl SiO2 (ODS), and Sephadex LH-20 open column chromatography. The structure of the compounds were determined based on spectroscopic analyses, including nuclear magnetic resonance (NMR), mass spectrometry (MS), circular dichroism (CD), and infrared (IR). In addition, compounds 1-4 were isolated for the first time from the root bark of M. alba in this study. PMID- 27563861 TI - Ball Milling Assisted Solvent and Catalyst Free Synthesis of Benzimidazoles and Their Derivatives. AB - Benzoic acid and o-phenylenediamine efficiently reacted under the green solvent free Ball Milling method. Several reaction parameters were investigated such as rotation frequency; milling balls weight and milling time. The optimum reaction condition was milling with 56.6 g weight of balls at 20 Hz frequency for one hour milling time. The study was extended for synthesis of a series of benzimidazol-2 one or benzimidazol-2-thione using different aldehydes; carboxylic acids; urea; thiourea or ammonium thiocyanate with o-phenylenediamine. Moreover; the alkylation of benzimidazolone or benzimidazolthione using ethyl chloroacetate was also studied. PMID- 27563862 TI - In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats. AB - Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch. Ham.ex D. Don. The present study was designed to investigate the metabolic profiles of FR429 in rats in vivo. Using liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF), total eight metabolites were found in rat bile and urine after intravenous administration of FR429, but could not be detected in plasma. These metabolites were ellagic acid, mono methylated FR429, ellagic acid methyl ether glucuronide, ellagic acid methyl ether diglucuronide, ellagic acid dimethyl ether glucuronide, and ellagic acid dimethyl ether diglucuronide. It was concluded that methylation and subsequent glucuronidation were the major metabolic pathways of FR429 in rats in vivo. This is the first report on the in vivo metabolism of the purified ellagitannin in rats. PMID- 27563863 TI - Stability, Antioxidant Capacity and Degradation Kinetics of Pelargonidin-3 glucoside Exposed to Ultrasound Power at Low Temperature. AB - As an alternative preservation method to thermal treatment, ultrasound is a novel non-thermal processing technology that can significantly avoid undesirable nutritional changes. However, recently literature indicated that anthocyanin degradation occurred when high amplitude ultrasound was applied to juice. This work mainly studied the effect of ultrasound on the stability and antioxidant capacity of pelargonidin-3-glucoside (Pg-3-glu) and the correlation between anthocyanin degradation and *OH generation in a simulated system. Results indicated that the spectral intensities of Pg-3-glu decreased with increasing ultrasound power (200-500 W) and treatment time (0-60 min). The degradation trend was consistent with first-order reaction kinetics (R2 > 0.9100). Further study showed that there was a good linear correlation between Pg-3-glu degradation and *OH production (R2 = 0.8790), which indicated the important role of *OH in the degradation of anthocyanin during ultrasound exposure. Moreover, a decrease in the antioxidant activity of solution(s) containing Pg-3-glu as evaluated by the DPPH and FRAP methods was observed after ultrasound treatment. PMID- 27563864 TI - Marine Toxin Okadaic Acid Affects the Immune Function of Bay Scallop (Argopecten irradians). AB - Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on the immune responses of bay scallop, Argopecten irradians. Various immunological parameters were assessed (total hemocyte counts (THC), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), and nitric oxide (NO) in the hemolymph of scallops at 3, 6, 12, 24, and 48 h post-exposure (hpe) to different concentrations of OA (50, 100, and 500 nM). Moreover, the expression of immune-system-related genes (CLT-6, FREP, HSP90, MT, and Cu/ZnSOD) was also measured. Results showed that ROS, MDA, and NO levels and LDH activity were enhanced after exposure to different concentrations of OA; however, both THC and GSH decreased between 24-48 hpe. The expression of immune-system-related genes was also assessed at different time points during the exposure period. Overall, our results suggest that exposure to OA had negative effects on immune system function, increased oxygenic stress, and disrupted metabolism of bay scallops. PMID- 27563865 TI - Neuroprotective Effects of a Standardized Flavonoid Extract from Safflower against a Rotenone-Induced Rat Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD. PMID- 27563867 TI - Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole. AB - Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also proceeded smoothly with several other synthetically useful activated trisubstituted olefins. The mild reaction conditions, short reaction times, and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting spiro-architectures. PMID- 27563866 TI - Quantification of Oxidized and Unsaturated Bile Alcohols in Sea Lamprey Tissues by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry. AB - A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted by n-hexane. Gradient UHPLC separation was performed using an Acquity BEH C18 column with a mobile phase of water and methanol containing 20 mM triethylamine. Multiple reaction monitoring modes of precursor-product ion transitions for each analyte was used. This method displayed good linearity, with correlation coefficients greater than 0.99, and was validated. Precision and accuracy (RSD %) were in the range of 0.31%-5.28%, while mean recoveries were between 84.3%-96.3%. With this technique, sea lamprey tissue samples were analyzed for unsaturated bile alcohol analytes. This method is practical and particularly suitable for widespread putative pheromone residue analysis. PMID- 27563868 TI - Truncation Derivatives of the S-Layer Protein of Sporosarcina ureae ATCC 13881 (SslA): Towards Elucidation of the Protein Domain Responsible for Self-Assembly. AB - The cell surface of Sporosarcina ureae ATCC 13881 is covered by an S-layer (SslA) consisting of identical protein subunits that assemble into lattices exhibiting square symmetry. In this work the self-assembly properties of the recombinant SslA were characterised with an emphasis on the identification of protein regions responsible for self-assembly. To this end, recombinant mature SslA (aa 31-1097) and three SslA truncation derivatives (one N-terminal, one C-terminal and one CN terminal) were produced in a heterologous expression system, isolated, purified and their properties analysed by in vitro recrystallisation experiments on a functionalised silicon wafer. As a result, recombinant mature SslA self-assembled into crystalline monolayers with lattices resembling the one of the wild-type SslA. The study identifies the central protein domain consisting of amino acids 341-925 self-sufficient for self-assembly. Neither the first 341 amino acids nor the last 172 amino acids of the protein sequence are required to self-assemble into lattices. PMID- 27563869 TI - Ionic Liquids as Solvents for Rhodium and Platinum Catalysts Used in Hydrosilylation Reaction. AB - A group of imidazolium and pyridinium based ionic liquids has been synthetized, and their ability to dissolve and activate the catalysts used in hydrosilylation reaction of 1-octane and 1,1,1,3,5,5,5-heptamethyltrisiloxane was investigated. An organometallic catalyst as well as inorganic complexes of platinum and rhodium dissolved in ionic liquids were used, forming liquid solutions not miscible with the substrates or with the products of the reaction. The results show that application of such a simple biphasic catalytic system enables reuse of ionic liquid phase with catalysts in multiple reaction cycles reducing the costs and decreasing the amount of catalyst needed per mole of product. PMID- 27563870 TI - Identification of a New Morpholine Scaffold as a P2Y12 Receptor Antagonist. AB - The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For this reason, ticagrelor-a new chemical class of P2Y12 receptor antagonist-was developed, but it can cause shortness of breath and various types of bleeding. Moreover, ticagrelor is a cytochrome P450 3A4 substrate/inhibitor and, therefore, caution should be exercised when it is used concomitantly with strong CYP3A4 inducers/inhibitors. There is a need for novel P2Y12 receptor antagonist scaffolds that are reversible and have high efficacy without associated side effects. Here, we describe a novel antagonist containing a morpholine moiety that was identified by screening libraries of commercially available compounds. The molecule, Compound E, acted on P2Y12, but not P2Y1 and P2Y13, and exhibited pharmacological characteristics that were distinct from those of ticagrelor, acting instead on P2Y12 via an allosteric mechanism. These results provide a basis for the development/optimization of a new class of P2Y12 antagonists. PMID- 27563871 TI - Adaptive Responses to Oxidative Stress in the Filamentous Fungal Shiraia bambusicola. AB - Shiraia bambusicola can retain excellent physiological activity when challenged with maximal photo-activated hypocrellin, which causes cellular oxidative stress. The protective mechanism of this fungus against oxidative stress has not yet been reported. We evaluated the biomass and hypocrellin biosynthesis of Shiraia sp. SUPER-H168 when treated with high concentrations of H2O2. Hypocrellin production was improved by nearly 27% and 25% after 72 h incubation with 10 mM and 20 mM H2O2, respectively, while the inhibition ratios of exogenous 20 mM H2O2 on wild S. bambusicola and a hypocrellin-deficient strain were 20% and 33%, respectively. Under exogenous oxidative stress, the specific activities of catalase, glutathione reductase, and superoxide dismutase were significantly increased. These changes may allow Shiraia to maintain normal life activities under oxidative stress. Moreover, sufficient glutathione peroxidase was produced in the SUPER-H168 and hypocrellin-deficient strains, to further ensure that S. bambusicola has excellent protective abilities against oxidative stress. This study creates the possibility that the addition of high H2O2 concentrations can stimulate fungal secondary metabolism, and will lead to a comprehensive and coherent understanding of mechanisms against oxidative stresses from high hydrogen peroxide concentrations in the filamentous fungal Shiraia sp. SUPER H168. PMID- 27563872 TI - Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate Derived Actinomycete Streptomyces sp. AB - As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3 isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC50 of 1.5 MUg/mL, while 1-10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives. PMID- 27563873 TI - Human TRIB2 Oscillates during the Cell Cycle and Promotes Ubiquitination and Degradation of CDC25C. AB - Tribbles homolog 2 (TRIB2) is a member of the mammalian Tribbles family of serine/threonine pseudokinases (TRIB1-3). Studies of TRIB2 indicate that many of the molecular interactions between the single Drosophila Tribbles (Trbl) protein and interacting partners are evolutionary conserved. In this study, we examined the relationship between TRIB2 and cell division cycle 25 (CDC25) family of dual specificity protein phosphatases (mammalian homologues of Drosophila String), which are key physiological cell cycle regulators. Using co-immunoprecipitation we demonstrate that TRIB2 interacts with CDC25B and CDC25C selectively. Forced overexpression of TRIB2 caused a marked decrease in total CDC25C protein levels. Following inhibition of the proteasome, CDC25C was stabilized in the nuclear compartment. This implicates TRIB2 as a regulator of nuclear CDC25C turnover. In complementary ubiquitination assays, we show that TRIB2-mediated degradation of CDC25C is associated with lysine-48-linked CDC25C polyubiquitination driven by the TRIB2 kinase-like domain. A cell cycle associated role for TRIB2 is further supported by the cell cycle regulated expression of TRIB2 protein levels. Our findings reveal mitotic CDC25C as a new target of TRIB2 that is degraded via the ubiquitin proteasome system. Inappropriate CDC25C regulation could mechanistically underlie TRIB2 mediated regulation of cellular proliferation in neoplastic cells. PMID- 27563874 TI - Antiplatelet Usage Impacts Clot Density in Acute Anterior Circulation Ischemic Stroke. AB - We explored whether clot density in middle cerebral artery (MCA) occlusion is related to clinical variables, stroke etiology, blood constituents, and prestroke medication. We performed a retrospective chart review of patients with acute ischemic stroke of the anterior circulation admitted to two Central European stroke centers. The acquisition of non-contrast enhanced CT (NECT) and CT angiography (CTA) within 4.5 h of symptom onset was obligatory. We assessed the site of MCA occlusion as well as density, area, and length of the clot in 150 patients. The Hounsfield unit values for the clot were divided with contralateral MCA segment to yield relative Hounsfield Unit ratio (rHU). The site of the vessel occlusion (M1 vs. M2) and antiplatelet usage, but not stroke etiology, significantly influenced rHU. We found an inverse correlation of rHU with erythrocyte count (p < 0.001). The multivariate analysis revealed that a higher rHU (i.e., clot being more hyperdense) was more likely with the use of antiplatelets (OR 4.24, CI 1.10-16.31, p = 0.036). Erythrocyte (OR 0.18, CI 0.05 0.55, p = 0.003), and thrombocyte counts (OR 0.99, CI 0.98-0.99, p = 0.029) were associated with odds for more hypodense clots (lower rHU). Our study disclosed that antiplatelet therapy impacts the composition of intracranial clots of the anterior circulation. PMID- 27563876 TI - Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells. AB - Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active oxygen species. Endothelial MT is not induced by inorganic zinc. Adequate tools are required to investigate the mechanisms underlying endothelial MT induction. In the present study, we found that an organoantimony compound, tris(pentafluorophenyl)stibane, induces gene expression of MT-1A and MT-2A, which are subisoforms of MT in bovine aortic endothelial cells. The data reveal that MT 1A is induced by activation of both the MTF-1-MRE and Nrf2-ARE pathways, whereas MT-2A expression requires only activation of the MTF-1-MRE pathway. The present data suggest that the original role of MT-1 is to protect cells from heavy metal toxicity and oxidative stress in the biological defense system, while that of MT 2 is to regulate intracellular zinc metabolism. PMID- 27563877 TI - MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression. AB - Chondrocyte hypertrophy, regulated by Runt-related transcription factor 2 (RUNX2) and matrix metalloproteinase 13 (MMP13), is a crucial step in cartilage degeneration and osteoarthritis (OA) pathogenesis. We previously demonstrated that microRNA-381 (miR-381) promotes MMP13 expression during chondrogenesis and contributes to cartilage degeneration; however, the mechanism underlying this process remained unclear. In this study, we observed divergent expression of miR 381 and histone deacetylase 4 (HDAC4), an enzyme that directly inhibits RUNX2 and MMP13 expression, during late-stage chondrogenesis of ATDC5 cells, as well as in prehypertrophic and hypertrophic chondrocytes during long bone development in E16.5 mouse embryos. We therefore investigated whether this miRNA regulates HDAC4 expression during chondrogenesis. Notably, overexpression of miR-381 inhibited HDAC4 expression but promoted RUNX2 expression. Moreover, transfection of SW1353 cells with an miR-381 mimic suppressed the activity of a reporter construct containing the 3'-untranslated region (3'-UTR) of HDAC4. Conversely, treatment with a miR-381 inhibitor yielded increased HDAC4 expression and decreased RUNX2 expression. Lastly, knockdown of HDAC4 expression resulted in increased RUNX2 and MMP13 expression in SW1353 cells. Collectively, our results indicate that miR-381 epigenetically regulates MMP13 and RUNX2 expression via targeting of HDAC4, thereby suggesting the possibilities of inhibiting miR-381 to control chondrocyte hypertrophy and cartilage degeneration. PMID- 27563875 TI - Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID- 27563878 TI - Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury. AB - Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL 1beta), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-alpha, IL-1beta, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-alpha and IL-1beta by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-alpha, IL-1beta, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI. PMID- 27563879 TI - Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form. AB - As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis. PMID- 27563881 TI - Physical, Chemical and Biochemical Modifications of Protein-Based Films and Coatings: An Extensive Review. AB - Protein-based films and coatings are an interesting alternative to traditional petroleum-based materials. However, their mechanical and barrier properties need to be enhanced in order to match those of the latter. Physical, chemical, and biochemical methods can be used for this purpose. The aim of this article is to provide an overview of the effects of various treatments on whey, soy, and wheat gluten protein-based films and coatings. These three protein sources have been chosen since they are among the most abundantly used and are well described in the literature. Similar behavior might be expected for other protein sources. Most of the modifications are still not fully understood at a fundamental level, but all the methods discussed change the properties of the proteins and resulting products. Mastering these modifications is an important step towards the industrial implementation of protein-based films. PMID- 27563882 TI - Hypoxia Suppresses Spontaneous Mineralization and Osteogenic Differentiation of Mesenchymal Stem Cells via IGFBP3 Up-Regulation. AB - Hypoxia has diverse stimulatory effects on human adipose-derived stem cells (ASCs). In the present study, we investigated whether hypoxic culture conditions (2% O2) suppress spontaneous mineralization and osteogenic differentiation of ASCs. We also investigated signaling pathways and molecular mechanisms involved in this process. We found that hypoxia suppressed spontaneous mineralization and osteogenic differentiation of ASCs, and up-regulated mRNA and protein expression of Insulin-like growth factor binding proteins (IGFBPs) in ASCs. Although treatment with recombinant IGFBPs did not affect osteogenic differentiation of ASCs, siRNA-mediated inhibition of IGFBP3 attenuated hypoxia-suppressed osteogenic differentiation of ASCs. In contrast, overexpression of IGFBP3 via lentiviral vectors inhibited ASC osteogenic differentiation. These results indicate that hypoxia suppresses spontaneous mineralization and osteogenic differentiation of ASCs via intracellular IGFBP3 up-regulation. We determined that reactive oxygen species (ROS) generation followed by activation of the MAPK and PI3K/Akt pathways play pivotal roles in IGFBP3 expression under hypoxia. For example, ROS scavengers and inhibitors for MAPK and PI3K/Akt pathways attenuated the hypoxia-induced IGFBP3 expression. Inhibition of Elk1 and NF-kappaB through siRNA transfection also led to down-regulation of IGFBP3 mRNA expression. We next addressed the proliferative potential of ASCs with overexpressed IGFBP3, but IGFBP3 overexpression reduced the proliferation of ASCs. In addition, hypoxia reduced the osteogenic differentiation of bone marrow-derived clonal mesenchymal stem cells. Collectively, our results indicate that hypoxia suppresses the osteogenic differentiation of mesenchymal stem cells via IGFBP3 up-regulation. PMID- 27563880 TI - Guidance of Signaling Activations by Cadherins and Integrins in Epithelial Ovarian Cancer Cells. AB - Epithelial ovarian cancer (EOC) is the deadliest tumor among gynecological cancer in the industrialized countries. The EOC incidence and mortality have remained unchanged over the last 30 years, despite the progress in diagnosis and treatment. In order to develop novel and more effective therapeutic approaches, the molecular mechanisms involved in EOC progression have been thoroughly investigated in the last few decades. At the late stage, peritoneal metastases originate from the attachment of small clusters of cancer cells that shed from the primary site and carried by the ascites adhere to the abdominal peritoneum or omentum. This behavior suggests that cell-cell or cell-matrix adhesion mechanisms regulate EOC growth and dissemination. Complex downstream signalings, which might be influenced by functional cross-talk between adhesion molecules and co expressed and activated signaling proteins, can affect the proliferation/survival and the migration/invasion of EOC cells. This review aimed to define the impact of the mechanisms of cell-cell, through cadherins, and cell-extracellular matrix adhesion, through integrins, on the signaling cascades induced by membrane receptors and cytoplasmic proteins known to have a role in the proliferation, migration and invasion of EOC cells. Finally, some novel approaches using peptidomimetic ligands to cadherin and integrins are summarized. PMID- 27563884 TI - Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model. AB - Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-kappaB (NFkappaB) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NFkappaB and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NFkappaB/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC. PMID- 27563883 TI - Effects of Hormone Therapy on Oxidative Stress in Postmenopausal Women with Metabolic Syndrome. AB - The aim of this study was to determine the effect of oral hormone therapy (HT) on oxidative stress (OS) in postmenopausal women with metabolic syndrome (MetS). A randomized, double blind, placebo-controlled trial was carried out. We formed four groups of 25 women each; healthy (HW) and MetS women (MSW) were assigned to HT (1 mg/day of estradiol valerate plus 5 mg/10 day of medroxiprogesterone) or placebo. We measured plasma lipoperoxides, erythrocyte superoxide dismutase and glutathione peroxidase, total plasma antioxidant status and uric acid, as OS markers. Alternative cut-off values of each parameter were defined and a stress score (SS) ranging from 0 to 7 was used as total OS. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. Participants were seen at baseline, 3 and 6 months. After 6 months, MetS decreased in MSW-HT (48%), their triglycerides and high-density lipoprotein cholesterol (HDL-c) improved; in the other groups no difference was found. SS in MSW-HT decreased (3.8 +/- 0.3 to 1.7 +/- 0.3, p < 0.05) and OS was also reduced (44%), this effect was evident since 3 mo. HW-HT with high OS also decreased (40%). In placebo groups there was no change. Our findings suggest that HT improve lipids and OS associated to MetS in postmenopausal women. PMID- 27563885 TI - Assessing the Effects of Acute Amyloid beta Oligomer Exposure in the Rat. AB - Alzheimer's disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid beta oligomers (AbetaO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AbetaO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Abeta, microglia, and cholinergic neurons. Rats exposed to AbetaO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Abeta was only observed in the corpus callosum surrounding the lateral ventricles. AbetaO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AbetaO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AbetaO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD. PMID- 27563886 TI - Bone Density as a Marker of Response to Radiotherapy in Bone Metastatic Lesions: A Review of the Published Data. AB - Metastases to the bone are presenting in a great percentage of patients with cancer, causing a variety of symptoms, affecting the quality of life and survival of patients. A multidisciplinary approach from different health providers is required for treatment, including radiation oncologists, medical oncologists and surgeons. The role of radiotherapy in the management of bone metastases has long been established through multiple randomized trials. The estimation of response to the therapy is subjective and is based on the palliation of the symptoms that the patients report. However, a quantification of the tumor burden and response to the treatment with the use of an objective method to measure those parameters is a clinical expectation in oncology. The change in bone density in affected areas (mainly lytic) after local radiotherapy, representing the cellular changes that have occurred, is a promising marker of response to treatment. PMID- 27563887 TI - Enhancing Signal Output and Avoiding BOD/Toxicity Combined Shock Interference by Operating a Microbial Fuel Cell Sensor with an Optimized Background Concentration of Organic Matter. AB - In the monitoring of pollutants in an aquatic environment, it is important to preserve water quality safety. Among the available analysis methods, the microbial fuel cell (MFC) sensor has recently been used as a sustainable and on line electrochemical microbial biosensor for biochemical oxygen demand (BOD) and toxicity, respectively. However, the effect of the background organic matter concentration on toxicity monitoring when using an MFC sensor is not clear and there is no effective strategy available to avoid the signal interference by the combined shock of BOD and toxicity. Thus, the signal interference by the combined shock of BOD and toxicity was systematically studied in this experiment. The background organic matter concentration was optimized in this study and it should be fixed at a high level of oversaturation for maximizing the signal output when the current change (DeltaI) is selected to correlate with the concentration of a toxic agent. When the inhibition ratio (IR) is selected, on the other hand, it should be fixed as low as possible near the detection limit for maximizing the signal output. At least two MFC sensors operated with high and low organic matter concentrations and a response chart generated from pre-experiment data were both required to make qualitative distinctions of the four types of combined shock caused by a sudden change in BOD and toxicity. PMID- 27563888 TI - Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound. AB - Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field. PMID- 27563889 TI - CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis. AB - The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05), when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR) domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA CTHRSSVVC) was synthesized and labeled with (111)InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases. PMID- 27563890 TI - Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload. AB - Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 MUM. Time of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 MUM, respectively. CW-33 significantly moderated JEV-triggered Ca(2+) overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt/mTOR and Jak/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I 2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt/mTOR and Jak/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents. PMID- 27563892 TI - Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF-kappaB Signaling Pathway. AB - Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-kappaB pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD(3+), CD(4+) and CD(8+) T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-kappaB pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-kappaB pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment. PMID- 27563893 TI - Performance and Durability of Thin Film Thermocouple Array on a Porous Electrode. AB - Management of solid oxide fuel cell (SOFC) thermal gradients is vital to limit thermal expansion mismatch and thermal stress. However, owing to harsh operation conditions of SOFCs and limited available space in stack configuration, the number of techniques available to obtain temperature distribution from the cell surface is limited. The authors previously developed and studied a thermocouple array pattern to detect surface temperature distribution on an SOFC in open circuit conditions. In this study, the performance in terms of mechanical durability and oxidation state of the thin film thermoelements of the thermocouple array on the porous SOFC cathode is investigated. A thin-film multi junction thermocouple array was sputter deposited using a magnetron sputter coater. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) characterisation techniques were carried out to understand characteristics of the thin film before and after temperature (20 degrees C-800 degrees C) measurement. Temperature readings from the sensor agreed well with the closely placed commercial thermocouple during heating segments. However, a sensor failure occurred at around 350 degrees C during the cooling segment. The SEM and XPS tests revealed cracks on the thin film thermoelements and oxidation to the film thickness direction. PMID- 27563891 TI - TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function. AB - Migration of vascular smooth muscle cells (VSMCs) into the intima is considered to be a vital event in the pathophysiology of atherosclerosis. Despite substantial evidence supporting the pathogenic role of Toll-like receptor 4 (TLR4) in the progression of atherogenesis, its function in the regulation of VSMC migration remains unclear. The goal of the present study was to elucidate the mechanism by which TLR4 regulates VSMC migration. Inhibitor experiments revealed that TLR4-induced IL-6 secretion and VSMC migration were mediated via the concerted actions of MyD88 and TRIF on the activation of p38 MAPK and ERK1/2 signaling. Neutralizing anti-IL-6 antibodies abrogated TLR4-driven VSMC migration and F-actin polymerization. Blockade of p38 MAPK or ERK1/2 signaling cascade inhibited TLR4 agonist-mediated activation of cAMP response element binding protein (CREB). Moreover, siRNA-mediated suppression of CREB production repressed TLR4-induced IL-6 production and VSMC migration. Rac-1 inhibitor suppressed TLR4 driven VSMC migration but not IL-6 production. Importantly, the serum level of IL 6 and TLR4 endogenous ligand HMGB1 was significantly higher in patients with coronary artery diseases (CAD) than in healthy subjects. Serum HMGB1 level was positively correlated with serum IL-6 level in CAD patients. The expression of both HMGB1 and IL-6 was clearly detected in the atherosclerotic tissue of the CAD patients. Additionally, there was a positive association between p-CREB and HMGB1 in mouse atherosclerotic tissue. Based on our findings, we concluded that, upon ligand binding, TLR4 activates p38 MAPK and ERK1/2 signaling through MyD88 and TRIF in VSMCs. These signaling pathways subsequently coordinate an additive augmentation of CREB-driven IL-6 production, which in turn triggers Rac-1 mediated actin cytoskeleton to promote VSMC migration. PMID- 27563894 TI - Sensitive Bioanalysis Based on in-Situ Droplet Anodic Stripping Voltammetric Detection of CdS Quantum Dots Label after Enhanced Cathodic Preconcentration. AB - We report a protocol of CdS-labeled sandwich-type amperometric bioanalysis with high sensitivity, on the basis of simultaneous chemical-dissolution/cathodic enrichment of the CdS quantum dot biolabel and anodic stripping voltammetry (ASV) detection of Cd directly on the bioelectrode. We added a microliter droplet of 0.1 M aqueous HNO3 to dissolve CdS on the bioelectrode and simultaneously achieved the potentiostatic cathodic preconcentration of Cd by starting the potentiostatic operation before HNO3 addition, which can largely increase the ASV signal. Our protocol was used for immunoanalysis and aptamer-based bioanalysis of several proteins, giving limits of detection of 4.5 fg.mL(-1) for human immunoglobulin G, 3.0 fg.mL(-1) for human carcinoembryonic antigen (CEA), 4.9 fg.mL(-1) for human alpha-fetoprotein (AFP), and 0.9 fM for thrombin, which are better than many reported results. The simultaneous and sensitive analysis of CEA and AFP at two screen-printed carbon electrodes was also conducted by our protocol. PMID- 27563895 TI - Introduction to the Special Issue on "State-of-the-Art Sensor Technology in Japan 2015". AB - This Special Issue, "State-of-the-Art Sensor Technology in Japan 2015", collected papers on different kinds of sensing technology: fundamental technology for intelligent sensors, information processing for monitoring humans, and information processing for adaptive and survivable sensor systems.[...]. PMID- 27563896 TI - Queuing Theory Based Co-Channel Interference Analysis Approach for High-Density Wireless Local Area Networks. AB - Increased co-channel interference (CCI) in wireless local area networks (WLANs) is bringing serious resource constraints to today's high-density wireless environments. CCI in IEEE 802.11-based networks is inevitable due to the nature of the carrier sensing mechanism however can be reduced by resource optimization approaches. That means the CCI analysis is basic, but also crucial for an efficient resource management. In this article, we present a novel CCI analysis approach based on the queuing theory, which considers the randomness of end users' behavior and the irregularity and complexity of network traffic in high density WLANs that adopts the M/M/c queuing model for CCI analysis. Most of the CCIs occur when multiple networks overlap and trigger channel contentions; therefore, we use the ratio of signal-overlapped areas to signal coverage as a probabilistic factor to the queuing model to analyze the CCI impacts in highly overlapped WLANs. With the queuing model, we perform simulations to see how the CCI influences the quality of service (QoS) in high-density WLANs. PMID- 27563897 TI - A Wideband Circularly Polarized Pixelated Dielectric Resonator Antenna. AB - The design of a wideband circularly polarized pixelated dielectric resonator antenna using a real-coded genetic algorithm (GA) is presented for far-field wireless power transfer applications. The antenna consists of a dielectric resonator (DR) which is discretized into 8 * 8 grid DR bars. The real-coded GA is utilized to estimate the optimal heights of the 64 DR bars to realize circular polarization. The proposed antenna is excited by a narrow rectangular slot etched on the ground plane. A prototype of the proposed antenna is fabricated and tested. The measured -10 dB reflection and 3 dB axial ratio bandwidths are 32.32% (2.62-3.63 GHz) and 14.63% (2.85-3.30 GHz), respectively. A measured peak gain of 6.13 dBic is achieved at 3.2 GHz. PMID- 27563898 TI - Practical Performance Analysis for Multiple Information Fusion Based Scalable Localization System Using Wireless Sensor Networks. AB - In practical localization system design, researchers need to consider several aspects to make the positioning efficiently and effectively, e.g., the available auxiliary information, sensing devices, equipment deployment and the environment. Then, these practical concerns turn out to be the technical problems, e.g., the sequential position state propagation, the target-anchor geometry effect, the Non line-of-sight (NLOS) identification and the related prior information. It is necessary to construct an efficient framework that can exploit multiple available information and guide the system design. In this paper, we propose a scalable method to analyze system performance based on the Cramer-Rao lower bound (CRLB), which can fuse all of the information adaptively. Firstly, we use an abstract function to represent all of the wireless localization system model. Then, the unknown vector of the CRLB consists of two parts: the first part is the estimated vector, and the second part is the auxiliary vector, which helps improve the estimation accuracy. Accordingly, the Fisher information matrix is divided into two parts: the state matrix and the auxiliary matrix. Unlike the theoretical analysis, our CRLB can be a practical fundamental limit to denote the system that fuses multiple information in the complicated environment, e.g., recursive Bayesian estimation based on the hidden Markov model, the map matching method and the NLOS identification and mitigation methods. Thus, the theoretical results are approaching the real case more. In addition, our method is more adaptable than other CRLBs when considering more unknown important factors. We use the proposed method to analyze the wireless sensor network-based indoor localization system. The influence of the hybrid LOS/NLOS channels, the building layout information and the relative height differences between the target and anchors are analyzed. It is demonstrated that our method exploits all of the available information for the indoor localization systems and serves as an indicator for practical system evaluation. PMID- 27563899 TI - A New Approach of Oil Spill Detection Using Time-Resolved LIF Combined with Parallel Factors Analysis for Laser Remote Sensing. AB - In hope of developing a method for oil spill detection in laser remote sensing, a series of refined and crude oil samples were investigated using time-resolved fluorescence in conjunction with parallel factors analysis (PARAFAC). The time resolved emission spectra of those investigated samples were taken by a laser remote sensing system on a laboratory basis with a detection distance of 5 m. Based on the intensity-normalized spectra, both refined and crude oil samples were well classified without overlapping, by the approach of PARAFAC with four parallel factors. Principle component analysis (PCA) has also been operated as a comparison. It turned out that PCA operated well in classification of broad oil type categories, but with severe overlapping among the crude oil samples from different oil wells. Apart from the high correct identification rate, PARAFAC has also real-time capabilities, which is an obvious advantage especially in field applications. The obtained results suggested that the approach of time-resolved fluorescence combined with PARAFAC would be potentially applicable in oil spill field detection and identification. PMID- 27563900 TI - Querying and Extracting Timeline Information from Road Traffic Sensor Data. AB - The escalation of traffic congestion in urban cities has urged many countries to use intelligent transportation system (ITS) centers to collect historical traffic sensor data from multiple heterogeneous sources. By analyzing historical traffic data, we can obtain valuable insights into traffic behavior. Many existing applications have been proposed with limited analysis results because of the inability to cope with several types of analytical queries. In this paper, we propose the QET (querying and extracting timeline information) system-a novel analytical query processing method based on a timeline model for road traffic sensor data. To address query performance, we build a TQ-index (timeline query index) that exploits spatio-temporal features of timeline modeling. We also propose an intuitive timeline visualization method to display congestion events obtained from specified query parameters. In addition, we demonstrate the benefit of our system through a performance evaluation using a Busan ITS dataset and a Seattle freeway dataset. PMID- 27563901 TI - Remote Bridge Deflection Measurement Using an Advanced Video Deflectometer and Actively Illuminated LED Targets. AB - An advanced video deflectometer using actively illuminated LED targets is proposed for remote, real-time measurement of bridge deflection. The system configuration, fundamental principles, and measuring procedures of the video deflectometer are first described. To address the challenge of remote and accurate deflection measurement of large engineering structures without being affected by ambient light, the novel idea of active imaging, which combines high brightness monochromatic LED targets with coupled bandpass filter imaging, is introduced. Then, to examine the measurement accuracy of the proposed advanced video deflectometer in outdoor environments, vertical motions of an LED target with precisely-controlled translations were measured and compared with prescribed values. Finally, by tracking six LED targets mounted on the bridge, the developed video deflectometer was applied for field, remote, and multipoint deflection measurement of the Wuhan Yangtze River Bridge, one of the most prestigious and most publicized constructions in China, during its routine safety evaluation tests. Since the proposed video deflectometer using actively illuminated LED targets offers prominent merits of remote, contactless, real-time, and multipoint deflection measurement with strong robustness against ambient light changes, it has great potential in the routine safety evaluation of various bridges and other large-scale engineering structures. PMID- 27563902 TI - An Adaptive Ship Detection Scheme for Spaceborne SAR Imagery. AB - With the rapid development of spaceborne synthetic aperture radar (SAR) and the increasing need of ship detection, research on adaptive ship detection in spaceborne SAR imagery is of great importance. Focusing on practical problems of ship detection, this paper presents a highly adaptive ship detection scheme for spaceborne SAR imagery. It is able to process a wide range of sensors, imaging modes and resolutions. Two main stages are identified in this paper, namely: ship candidate detection and ship discrimination. Firstly, this paper proposes an adaptive land masking method using ship size and pixel size. Secondly, taking into account the imaging mode, incidence angle, and polarization channel of SAR imagery, it implements adaptive ship candidate detection in spaceborne SAR imagery by applying different strategies to different resolution SAR images. Finally, aiming at different types of typical false alarms, this paper proposes a comprehensive ship discrimination method in spaceborne SAR imagery based on confidence level and complexity analysis. Experimental results based on RADARSAT 1, RADARSAT-2, TerraSAR-X, RS-1, and RS-3 images demonstrate that the adaptive scheme proposed in this paper is able to detect ship targets in a fast, efficient and robust way. PMID- 27563904 TI - Influence of Experimental Conditions on Electronic Tongue Results-Case of Valsartan Minitablets Dissolution. AB - A potentiometric electronic tongue was applied to study the release of valsartan from pharmaceutical formulations, i.e., minitablets uncoated and coated with Eudragit E. Special attention was paid to evaluate the influence of medium temperature and composition, as well as to compare the performances of the sensor arrays working in various hydrodynamic conditions. The drug dissolution profiles registered with the ion-sensitive electrodes were compared with standard dissolution tests performed with USP Apparatus 2 (paddle). Moreover, the signal changes of all sensors were processed by principal component analysis to visualize the release modifications, related to the presence of the coating agent. Finally, the importance and influence of the experimental conditions on the results obtained using potentiometric sensor arrays were discussed. PMID- 27563903 TI - Towards a Graphene-Based Low Intensity Photon Counting Photodetector. AB - Graphene is a highly promising material in the development of new photodetector technologies, in particular due its tunable optoelectronic properties, high mobilities and fast relaxation times coupled to its atomic thinness and other unique electrical, thermal and mechanical properties. Optoelectronic applications and graphene-based photodetector technology are still in their infancy, but with a range of device integration and manufacturing approaches emerging this field is progressing quickly. In this review we explore the potential of graphene in the context of existing single photon counting technologies by comparing their performance to simulations of graphene-based single photon counting and low photon intensity photodetection technologies operating in the visible, terahertz and X-ray energy regimes. We highlight the theoretical predictions and current graphene manufacturing processes for these detectors. We show initial experimental implementations and discuss the key challenges and next steps in the development of these technologies. PMID- 27563906 TI - Are We Ready to Build a System for Assisting Blind People in Tactile Exploration of Bas-Reliefs? AB - Nowadays, the creation of methodologies and tools for facilitating the 3D reproduction of artworks and, contextually, to make their exploration possible and more meaningful for blind users is becoming increasingly relevant in society. Accordingly, the creation of integrated systems including both tactile media (e.g., bas-reliefs) and interfaces capable of providing the users with an experience cognitively comparable to the one originally envisioned by the artist, may be considered the next step for enhancing artworks exploration. In light of this, the present work provides a description of a first-attempt system designed to aid blind people (BP) in the tactile exploration of bas-reliefs. In detail, consistent hardware layout, comprising a hand-tracking system based on Kinect((r)) sensor and an audio device, together with a number of methodologies, algorithms and information related to physical design are proposed. Moreover, according to experimental test on the developed system related to the device position, some design alternatives are suggested so as to discuss pros and cons. PMID- 27563905 TI - Ultrasensitive, Label Free, Chemiresistive Nanobiosensor Using Multiwalled Carbon Nanotubes Embedded Electrospun SU-8 Nanofibers. AB - This paper reports the synthesis and fabrication of aligned electrospun nanofibers derived out of multiwalled carbon nanotubes (MWCNTs) embedded SU-8 photoresist, which are targeted towards ultrasensitive biosensor applications. The ultrasensitivity (detection in the range of fg/mL) and the specificity of these biosensors were achieved by complementing the inherent advantages of MWCNTs such as high surface to volume ratio and excellent electrical and transduction properties with the ease of surface functionalization of SU-8. The electrospinning process was optimized to precisely align nanofibers in between two electrodes of a copper microelectrode array. MWCNTs not only enhance the conductivity of SU-8 nanofibers but also act as transduction elements. In this paper, MWCNTs were embedded way beyond the percolation threshold and the optimum percentage loading of MWCNTs for maximizing the conductivity of nanofibers was figured out experimentally. As a proof of concept, the detection of myoglobin, an important biomarker for on-set of Acute Myocardial Infection (AMI) has been demonstrated by functionalizing the nanofibers with anti-myoglobin antibodies and carrying out detection using a chemiresistive method. This simple and robust device yielded a detection limit of 6 fg/mL. PMID- 27563907 TI - The Finite Element Analysis for a Mini-Conductance Probe in Horizontal Oil-Water Two-Phase Flow. AB - Oil-water two-phase flow is widespread in petroleum industry processes. The study of oil-water two-phase flow in horizontal pipes and the liquid holdup measurement of oil-water two-phase flow are of great importance for the optimization of the oil production process. This paper presents a novel sensor, i.e., a mini conductance probe (MCP) for measuring pure-water phase conductivity of oil-water segregated flow in horizontal pipes. The MCP solves the difficult problem of obtaining the pure-water correction for water holdup measurements by using a ring shaped conductivity water-cut meter (RSCWCM). Firstly, using the finite element method (FEM), the spatial sensitivity field of the MCP is investigated and the optimized MCP geometry structure is determined in terms of the characteristic parameters. Then, the responses of the MCP for the oil-water segregated flow are calculated, and it is found that the MCP has better stability and sensitivity to the variation of water-layer thickness in the condition of high water holdup and low flow velocity. Finally, the static experiments for the oil-water segregated flow were carried out and a novel calibration method for pure-water phase conductivity measurements was presented. The validity of the pure-water phase conductivity measurement with segregated flow in horizontal pipes was verified by experimental results. PMID- 27563908 TI - Design Methodology for Magnetic Field-Based Soft Tri-Axis Tactile Sensors. AB - Tactile sensors are essential if robots are to safely interact with the external world and to dexterously manipulate objects. Current tactile sensors have limitations restricting their use, notably being too fragile or having limited performance. Magnetic field-based soft tactile sensors offer a potential improvement, being durable, low cost, accurate and high bandwidth, but they are relatively undeveloped because of the complexities involved in design and calibration. This paper presents a general design methodology for magnetic field based three-axis soft tactile sensors, enabling researchers to easily develop specific tactile sensors for a variety of applications. All aspects (design, fabrication, calibration and evaluation) of the development of tri-axis soft tactile sensors are presented and discussed. A moving least square approach is used to decouple and convert the magnetic field signal to force output to eliminate non-linearity and cross-talk effects. A case study of a tactile sensor prototype, MagOne, was developed. This achieved a resolution of 1.42 mN in normal force measurement (0.71 mN in shear force), good output repeatability and has a maximum hysteresis error of 3.4%. These results outperform comparable sensors reported previously, highlighting the efficacy of our methodology for sensor design. PMID- 27563909 TI - Interference Confocal Microscope Integrated with Spatial Phase Shifter. AB - We present an interference confocal microscope (ICM) with a new single-body four step simultaneous phase-shifter device designed to obtain high immunity to vibration. The proposed ICM combines the respective advantages of simultaneous phase shifting interferometry and bipolar differential confocal microscopy to obtain high axis resolution, large dynamic range, and reduce the sensitivity to vibration and reflectance disturbance seamlessly. A compact single body spatial phase shifter is added to capture four phase-shifted interference signals simultaneously without time delay and construct a stable and space-saving simplified interference confocal microscope system. The test result can be obtained by combining the interference phase response and the bipolar property of differential confocal microscopy without phase unwrapping. Experiments prove that the proposed microscope is capable of providing stable measurements with 1 nm of axial depth resolution for either low- or high-numerical aperture objective lenses. PMID- 27563910 TI - Investigation of a Fiberoptic Device Based on a Long Period Grating in a Ring Resonator. AB - A fiberoptic architecture based on a ring resonator (RR) including a typical long period grating (LPG) was investigated. The interactions between the fundamental core mode (LP01 or HE11) coupled to the RR and the cladding mode (LP08), excited into the cavity by means of the LPG, allow a peculiar spectral response characterized by two splitting resonances to be achieved. The new LPGRR architecture is investigated theoretically and a mathematical modelling based on the transfer matrix method (TMM) is proposed. The theoretical results are compared with the experiments measured by an open-loop LPG, while the performance of the relative LPGRR was estimated by a theoretical parametric analysis. Finally, an overview of the possible LPGRR sensing applications is provided by investigating the features of a strain sensor operating in different environmental conditions. PMID- 27563911 TI - A Participatory Agent-Based Simulation for Indoor Evacuation Supported by Google Glass. AB - Indoor evacuation systems are needed for rescue and safety management. One of the challenges is to provide users with personalized evacuation routes in real time. To this end, this project aims at exploring the possibilities of Google Glass technology for participatory multiagent indoor evacuation simulations. Participatory multiagent simulation combines scenario-guided agents and humans equipped with Google Glass that coexist in a shared virtual space and jointly perform simulations. The paper proposes an architecture for participatory multiagent simulation in order to combine devices (Google Glass and/or smartphones) with an agent-based social simulator and indoor tracking services. PMID- 27563912 TI - Recent Advances of MEMS Resonators for Lorentz Force Based Magnetic Field Sensors: Design, Applications and Challenges. AB - Microelectromechanical systems (MEMS) resonators have allowed the development of magnetic field sensors with potential applications such as biomedicine, automotive industry, navigation systems, space satellites, telecommunications and non-destructive testing. We present a review of recent magnetic field sensors based on MEMS resonators, which operate with Lorentz force. These sensors have a compact structure, wide measurement range, low energy consumption, high sensitivity and suitable performance. The design methodology, simulation tools, damping sources, sensing techniques and future applications of magnetic field sensors are discussed. The design process is fundamental in achieving correct selection of the operation principle, sensing technique, materials, fabrication process and readout systems of the sensors. In addition, the description of the main sensing systems and challenges of the MEMS sensors are discussed. To develop the best devices, researches of their mechanical reliability, vacuum packaging, design optimization and temperature compensation circuits are needed. Future applications will require multifunctional sensors for monitoring several physical parameters (e.g., magnetic field, acceleration, angular ratio, humidity, temperature and gases). PMID- 27563914 TI - Evaluation of the Accuracy of Capillary Hydroxybutyrate Measurement Compared with Other Measurements in the Diagnosis of Diabetic Ketoacidosis: A Systematic Review. AB - A complication of diabetes is diabetic ketoacidosis (DKA), which if left untreated is a life threatening condition. Prompt and accurate diagnosis of DKA is required for the commencement of life saving interventions. Measurements of ketone bodies in DKA have usually been through nitroprusside urine acetoacetate testing. The aim of this systematic review was to examine whether capillary beta hydroxybutyrate (beta-OHB) testing is more accurate compared to other diagnostic methods of DKA. The following electronic databases were searched: EBSCO Host, MEDLINE, PSYCHInfo, CINAHL and Science Direct for publications from 1 January 2005 and up to and including 1 January 2016. Inclusion criteria were: Adults 18 years and over and known type 1 or type 2 diabetes. Retrospective and prospective observation studies were included. A total of nine studies met the inclusion criteria. Capillary beta-OHB was found to have high sensitivity, specificity, positive predictive value and negative predictive value in identifying DKA compared to urinary ketone testing. PMID- 27563913 TI - TRPV1: A Target for Rational Drug Design. AB - Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective, Ca(2+) permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX). Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures. PMID- 27563915 TI - Confirming the Environmental Concerns of Community Members Utilizing Participatory-Based Research in the Houston Neighborhood of Manchester. AB - In the last few decades, there has been an increase in community-based participatory research being conducted within the United States. Recent research has demonstrated that working with local community organizations, interest groups, and individuals can assist in the creation of, and sustainability in, health initiatives, adoption of emergency protocols, and potentially improve health outcomes for at-risk populations. However little research has assessed if communal concerns over environmental contaminants would be confirmed through environmental research. This cross-sectional study collected survey data and performed surface water analysis for heavy metals in a small neighborhood in Houston, TX, which is characterized by industrial sites, unimproved infrastructure, nuisance flooding, and poor air quality. Surveys were completed with 109 residents of the Manchester neighborhood. Water samples were taken from thirty zones within the neighborhood and assessed for arsenic (As), barium (Ba), cadmium (Cd), chromium (Cr), lead (Pb), selenium (Se), silver (Ag), and mercury (Hg). Survey results showed that the vast majority of all respondents were concerned over proximity to industry and waste facilities, as well as exposure to standing surface water. Barium was discovered in every sample and many of the zones showed alarming levels of certain metals. For example, one zone, two blocks from a public park, showed levels of arsenic at 180 (MUg/L), barium at 3296 (MUg/L), chromium at 363 (MUg/L), lead at 1448 (MUg/L), and mercury at 10 (MUg/L). These findings support the hypothesis that neighborhood members are aware of the issues affecting their community and can offer researchers valuable assistance in every stage of study design and execution. PMID- 27563916 TI - Evaluating Mobile Survey Tools (MSTs) for Field-Level Monitoring and Data Collection: Development of a Novel Evaluation Framework, and Application to MSTs for Rural Water and Sanitation Monitoring. AB - Information and communications technologies (ICTs) such as mobile survey tools (MSTs) can facilitate field-level data collection to drive improvements in national and international development programs. MSTs allow users to gather and transmit field data in real time, standardize data storage and management, automate routine analyses, and visualize data. Dozens of diverse MST options are available, and users may struggle to select suitable options. We developed a systematic MST Evaluation Framework (EF), based on International Organization for Standardization/International Electrotechnical Commission (ISO/IEC) software quality modeling standards, to objectively assess MSTs and assist program implementers in identifying suitable MST options. The EF is applicable to MSTs for a broad variety of applications. We also conducted an MST user survey to elucidate needs and priorities of current MST users. Finally, the EF was used to assess seven MSTs currently used for water and sanitation monitoring, as a validation exercise. The results suggest that the EF is a promising method for evaluating MSTs. PMID- 27563917 TI - Nutrition in the First 1000 Days: The Origin of Childhood Obesity. AB - Childhood obesity is a major global issue. Its incidence is constantly increasing, thereby offering a threatening public health perspective. The risk of developing the numerous chronic diseases associated with this condition from very early in life is significant. Although complex and multi-factorial, the pathophysiology of obesity recognizes essential roles of nutritional and metabolic aspects. Particularly, several risk factors identified as possible determinants of later-life obesity act within the first 1000 days of life (i.e., from conception to age 2 years). The purpose of this manuscript is to review those key mechanisms for which a role in predisposing children to obesity is supported by the most recent literature. Throughout the development of the human feeding environment, three different stages have been identified: (1) the prenatal period; (2) breast vs. formula feeding; and (3) complementary diet. A deep understanding of the specific nutritional challenges presented within each phase might foster the development of future preventive strategies. PMID- 27563918 TI - Association between Serum Uric Acid and Elevated Alanine Aminotransferase in the General Population. AB - BACKGROUND: Both the serum uric acid (SUA) level and elevated alanine aminotransferase (ALT) are related to metabolic syndrome. However, the association between SUA and elevated ALT has not been elucidated in the general population. The objective of this study was to investigate the association between SUA and elevated ALT in the general population of China; METHODS: A total of 11,572 adults (>=35 years of age) participated in this survey. Elevated ALT was defined as >40 U/L. SUA >= 7.0 mg/dL in males or >=6.0 mg/dL in females was defined as hyperuricemia. SUA within the reference range was divided into quartiles, and its associations with elevated ALT were evaluated by logistic regressions; RESULTS: A total of 7.4% participants had elevated ALT. The prevalence of hyperuricemia was 14.9% in males and 7.3% in females. There was a significantly positive dose-response association between SUA levels and the prevalence of elevated ALT. After adjusting for potential confounders, a positive relationship for elevated ALT was observed in subjects with hyperuricemia (odds ratio [OR]: 2.032, 95% confidence interval [CI]: 1.443-2.861 for men; OR: 2.045, 95% CI: 1.221-3.425 for women, both p < 0.05). Within the reference range, the association between SUA and elevated ALT persisted in the fourth quartile (OR: 1.467, 95% CI: 1.063-2.025 for men; OR: 1.721, 95% CI: 1.146-2.585 for women, both p < 0.05); CONCLUSIONS: Our results indicated that an increased SUA level, even within the reference range, was independently associated with elevated ALT in Chinese adults. PMID- 27563919 TI - The Relationships between Human Fatigue and Public Health: A Brief Commentary on Selected Papers from the 9th International Conference on Managing Fatigue in Transportation, Resources and Health. AB - The 9th International Conference on Managing Fatigue in Transportation, Resources and Health was held in Fremantle, Western Australia in March 2015. The purpose of the conferences in this series is to provide a forum for industry representatives, regulators, and scientists to discuss recent advances in the field of fatigue research. We have produced a Special Issue of the International Journal of Environmental Research and Public Health based on papers from the conference that were focused on various aspects of public health. First, the Special Issue highlights the fact that working long shifts and/or night shifts can affect not only cognitive functioning, but also physical health. In particular, three papers examined the potential relationships between shiftwork and different aspects of health, including the cardiovascular system, sleep disordered breathing, and eating behaviour. Second, the Special Issue highlights the move away from controlling fatigue through prescriptive hours of service rules and toward the application of risk management principles. In particular, three papers indicated that best-practice fatigue risk management systems should contain multiple redundant layers of defense against fatigue-related errors and accidents. PMID- 27563920 TI - Iodine Nutritional Status of School Children in Nauru 2015. AB - Little is known about iodine nutritional status in island countries in the Pacific Ocean. The primary objective of this study was to report for the first time the iodine nutritional status of people in Nauru. In addition, sources of iodine nutrition (i.e., water and salt) were investigated. A school-based cross sectional survey of children aged 6-12 years was conducted in three primary schools of Nauru. Urinary iodine concentration (UIC) was determined by spot urine samples. Available water and salt samples in Nauru were collected for the measurement of iodine content. A food frequency questionnaire was conducted. The median UIC was 142 MUg/L, and 25.2% and 7.4% of the population had median UIC below 100 MUg/L and 50 MUg/L, respectively. Natural iodine-containing foods such as seaweeds and agar were rare. Iodine was undetectable in Nauruan tank water, filtered tap water, and raindrops. Of the analyzed salt products, five kinds were non-iodized, and three were iodized (iodine content: 15 ppm, 65 ppm, and 68 ppm, respectively). The results indicate that the iodine status in Nauruan school children is adequate. Iodized salt may serve as an important source of iodine nutrition in Nauru. PMID- 27563921 TI - The Reproducibility and Relative Validity of a Mexican Diet Quality Index (ICDMx) for the Assessment of the Habitual Diet of Adults. AB - The study of diet quality in a population provides information for the development of programs to improve nutritional status through better directed actions. The aim of this study was to assess the reproducibility and relative validity of a Mexican Diet Quality Index (ICDMx) for the assessment of the habitual diet of adults. The ICDMx was designed to assess the characteristics of a healthy diet using a validated semi-quantitative food frequency questionnaire (FFQ-Mx). Reproducibility was determined by comparing 2 ICDMx based on FFQs (one year interval). Relative validity was assessed by comparing the ICDMx (2nd FFQ) with that estimated based on the intake averages from dietary records (nine days). The questionnaires were answered by 97 adults (mean age in years = 27.5, SD = 12.6). Pearson (r) and intraclass correlations (ICC) were calculated; Bland Altman plots, Cohen's kappa coefficients and blood lipid determinations complemented the analysis. Additional analysis compared ICDMx scores with nutrients derived from dietary records, using a Pearson correlation. These nutrient intakes were transformed logarithmically to improve normality (log10) and adjusted according to energy, prior to analyses. The ICDMx obtained ICC reproducibility values ranged from 0.33 to 0.87 (23/24 items with significant correlations; mean = 0.63), while relative validity ranged from 0.26 to 0.79 (mean = 0.45). Bland-Altman plots showed a high level of agreement between methods. ICDMx scores were inversely correlated (p < 0.05) with total blood cholesterol (r = -0.33) and triglycerides (r = -0.22). ICDMx (as calculated from FFQs and DRs) obtained positive correlations with fiber, magnesium, potassium, retinol, thiamin, riboflavin, pyridoxine, and folate. The ICDMx obtained acceptable levels of reproducibility and relative validity in this population. It can be useful for population nutritional surveillance and to assess the changes resulting from the implementation of nutritional interventions. PMID- 27563922 TI - Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring. AB - Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 +/- 0.84 vs. 2.99 +/- 0.47 MUg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID- 27563923 TI - Aflatoxin B1 and M1 Degradation by Lac2 from Pleurotus pulmonarius and Redox Mediators. AB - Laccases (LCs) are multicopper oxidases that find application as versatile biocatalysts for the green bioremediation of environmental pollutants and xenobiotics. In this study we elucidate the degrading activity of Lac2 pure enzyme form Pleurotus pulmonarius towards aflatoxin B1 (AFB1) and M1 (AFM1). LC enzyme was purified using three chromatographic steps and identified as Lac2 through zymogram and LC-MS/MS. The degradation assays were performed in vitro at 25 degrees C for 72 h in buffer solution. AFB1 degradation by Lac2 direct oxidation was 23%. Toxin degradation was also investigated in the presence of three redox mediators, (2,2'-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid]) (ABTS) and two naturally-occurring phenols, acetosyringone (AS) and syringaldehyde (SA). The direct effect of the enzyme and the mediated action of Lac2 with redox mediators univocally proved the correlation between Lac2 activity and aflatoxins degradation. The degradation of AFB1 was enhanced by the addition of all mediators at 10 mM, with AS being the most effective (90% of degradation). AFM1 was completely degraded by Lac2 with all mediators at 10 mM. The novelty of this study relies on the identification of a pure enzyme as capable of degrading AFB1 and, for the first time, AFM1, and on the evidence that the mechanism of an effective degradation occurs via the mediation of natural phenolic compounds. These results opened new perspective for Lac2 application in the food and feed supply chains as a biotransforming agent of AFB1 and AFM1. PMID- 27563924 TI - The Dinoflagellate Toxin 20-Methyl Spirolide-G Potently Blocks Skeletal Muscle and Neuronal Nicotinic Acetylcholine Receptors. AB - The cyclic imine toxin 20-methyl spirolide G (20-meSPX-G), produced by the toxigenic dinoflagellate Alexandrium ostenfeldii/Alexandrium peruvianum, has been previously reported to contaminate shellfish in various European coastal locations, as revealed by mouse toxicity bioassay. The aim of the present study was to determine its toxicological profile and its molecular target selectivity. 20-meSPX-G blocked nerve-evoked isometric contractions in isolated mouse neuromuscular preparations, while it had no action on contractions elicited by direct electrical stimulation, and reduced reversibly nerve-evoked compound muscle action potential amplitudes in anesthetized mice. Voltage-clamp recordings in Xenopus oocytes revealed that 20-meSPX-G potently inhibited currents evoked by ACh on Torpedo muscle-type and human alpha7 nicotinic acetylcholine receptors (nAChR), whereas lower potency was observed in human alpha4beta2 nAChR. Competition-binding assays showed that 20-meSPX-G fully displaced [3H]epibatidine binding to HEK-293 cells expressing the human alpha3beta2 (Ki = 0.040 nM), whereas a 90-fold lower affinity was detected in human alpha4beta2 nAChR. The spirolide displaced [(125)I]alpha-bungarotoxin binding to Torpedo membranes (Ki = 0.028 nM) and in HEK-293 cells expressing chick chimeric alpha7-5HT3 nAChR (Ki = 0.11 nM). In conclusion, this is the first study to demonstrate that 20-meSPX-G is a potent antagonist of nAChRs, and its subtype selectivity is discussed on the basis of molecular docking models. PMID- 27563925 TI - Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90. AB - BACKGROUND: Prostate cancer-associated fibroblasts (CAF) can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; METHODS: We isolated CAF from prostate cancer patients of Gleason Score 6-10 and confirmed their cancer promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90) inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; RESULTS: HSP90 inhibitors dipalmitoyl-radicicol and 17 dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFbeta2) levels in CAF; CONCLUSIONS: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment. PMID- 27563926 TI - A Good Death? Report of the Second Newcastle Meeting on Laboratory Animal Euthanasia. AB - Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there is a lack of consensus regarding what methods of killing are humane for many species and stages of development. In 2013, an international group of researchers and stakeholders met at Newcastle University, United Kingdom to discuss the latest research and which methods could currently be considered most humane for the most commonly used laboratory species (mice, rats and zebrafish). They also discussed factors to consider when making decisions about appropriate techniques for particular species and projects, and priorities for further research. This report summarises the research findings and discussions, with recommendations to help inform good practice for humane killing. PMID- 27563927 TI - Three-Class EEG-Based Motor Imagery Classification Using Phase-Space Reconstruction Technique. AB - Over the last few decades, brain signals have been significantly exploited for brain-computer interface (BCI) applications. In this paper, we study the extraction of features using event-related desynchronization/synchronization techniques to improve the classification accuracy for three-class motor imagery (MI) BCI. The classification approach is based on combining the features of the phase and amplitude of the brain signals using fast Fourier transform (FFT) and autoregressive (AR) modeling of the reconstructed phase space as well as the modification of the BCI parameters (trial length, trial frequency band, classification method). We report interesting results compared with those present in the literature by utilizing sequential forward floating selection (SFFS) and a multi-class linear discriminant analysis (LDA), our findings showed superior classification results, a classification accuracy of 86.06% and 93% for two BCI competition datasets, with respect to results from previous studies. PMID- 27563928 TI - Adult Status Epilepticus: A Review of the Prehospital and Emergency Department Management. AB - Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second- and third-line pharmacological agents. PMID- 27563929 TI - Biopsychosocial Characteristics, Using a New Functional Measure of Balance, of an Elderly Population with CLBP. AB - This study examined the biopsychosocial characteristics of chronic low back pain (CLBP) in an understudied but increasingly larger part of the population: the elderly (i.e., 65 years and older). A new innovative physical functioning measure (postural control, which is a proxy for the common problem of slips and falls in the elderly) was part of this biopsychosocial evaluation. Also, the National Institutes of Health (NIH)-developed Patient-Reported Outcome Measurement Information System (PROMIS) was also part of this comprehensive evaluation. Two demographically-matched groups of elderly participants were evaluated: one with CLBP (n = 24); and the other without (NCLBP, n = 24). Results revealed significant differences in most of these measures between the two groups, further confirming the importance of using a biopsychosocial approach for future studies of pain and postural control in the elderly. PMID- 27563930 TI - Orientation selectivity in rat primary visual cortex emerges earlier with low contrast and high-luminance stimuli. AB - In natural vision, rapid and sustained variations in luminance and contrast change the reliability of information available about a visual scene, and markedly affect both neuronal and behavioural responses. The hallmark property of neurons in primary visual cortex (V1), orientation selectivity, is unaffected by changes in stimulus contrast, but it remains unclear how sustained differences in mean luminance and contrast affect the time-course of orientation selectivity, and the amount of information that neurons carry about orientation. We used reverse correlation with characterize the temporal dynamics of orientation selectivity in rat V1 neurons under four luminance-contrast conditions. We show that orientation selectivity and mutual information between neuronal responses and stimulus orientation are invariant to contrast or mean luminance. Critically, the time-course of the emergence of orientation selectivity was affected by both factors; response latencies were longer for low- than high-luminance gratings, and surprisingly, response latencies were also longer for high- than low-contrast gratings. Modelling suggests that luminance-modulated changes in feedforward gain, in combination with hyperpolarization caused by high contrasts can account for our physiological data. The hyperpolarization at high contrasts may increase signal-to-noise ratios, whereas a more depolarized membrane may lead to greater sensitivity to weak stimuli. PMID- 27563931 TI - Correction to Measuring Personal Exposure to Organophosphate Flame Retardants using Silicone Wristbands and Hand Wipes. PMID- 27563932 TI - High-Conductance Pathways in Ring-Strained Disilanes by Way of Direct sigma-Si-Si to Au Coordination. AB - A highly conducting electronic contact between a strained disilane and Au is demonstrated through scanning tunneling microscope-based single-molecule measurements. Conformationally locked cis diastereomers of bis(sulfide)-anchor equipped 1,2-disilaacenaphthenes readily form high-conducting junctions in which the two sulfide anchors bind in a bipodal fashion to one gold electrode, providing enough stability for a stable electrical contact between the Si-Si sigma bond and the other electrode. PMID- 27563933 TI - Vanadium(V) Complexes with Substituted 1,5-bis(2 hydroxybenzaldehyde)carbohydrazones and Their Use As Catalyst Precursors in Oxidation of Cyclohexane. AB - Six dinuclear vanadium(V) complexes have been synthesized: NH4[(VO2)2((H)LH)] (NH4[1]), NH4[(VO2)2((t-Bu)LH)] (NH4[2]), NH4[(VO2)2((Cl)LH)] (NH4[3]), [(VO2)(VO)((H)LH)(CH3O)] (4), [(VO2)(VO)((t-Bu)LH)(C2H5O)] (5), and [(VO2)(VO)((Cl)LH)(CH3O)(CH3OH/H2O)] (6) (where (H)LH4 = 1,5-bis(2 hydroxybenzaldehyde)carbohydrazone, (t-Bu)LH4 = 1,5-bis(3,5-di-tert-butyl-2 hydroxybenzaldehyde)carbohydrazone, and (Cl)LH4 = 1,5-bis(3,5-dichloro-2 hydroxybenzaldehyde)carbohydrazone). The structures of NH4[1] and 4-6 have been determined by X-ray diffraction (XRD) analysis. In all complexes, the triply deprotonated ligand accommodates two V ions, using two different binding sites ONN and ONO separated by a diazine unit -N-N-. In two pockets of NH4[1], two identical VO2(+) entities are present, whereas, in those of 4-6, two different VO2(+) and VO(3+) are bound. The highest oxidation state of V ions was corroborated by X-ray data, indicating the presence of alkoxido ligand bound to VO(3+) in 4-6, charge density measurements on 4, magnetic susceptibility, NMR spectroscopy, spectroelectrochemistry, and density functional theory (DFT) calculations. All four complexes characterized by XRD form dimeric associates in the solid state, which, however, do not remain intact in solution. Compounds NH4[1], NH4[2], and 4-6 were applied as alternative selective homogeneous catalysts for the industrially significant oxidation of cyclohexane to cyclohexanol and cyclohexanone. The peroxidative (with tert-butyl hydroperoxide, TBHP) oxidation of cyclohexane was performed under solvent-free and additive-free conditions and under low-power microwave (MW) irradiation. Cyclohexanol and cyclohexanone were the only products obtained (high selectivity), after 1.5 h of MW irradiation. Theoretical calculations suggest a key mechanistic role played by the carbohydrazone ligand, which can undergo reduction, instead of the metal itself, to form an active reduced form of the catalyst. PMID- 27563934 TI - Dry Powder Inhaler Delivery of Tobramycin in In Vitro Models of Tracheostomized Children. AB - BACKGROUND: Pediatric tracheostomies are not uncommon and aerosols allow for targeted lung therapy. However, there is little literature that quantifies aerosol delivery through tracheostomies. Nebulizers are commonly used in delivering tobramycin, but there are drawbacks, for example, time burden. Dry powder inhalers (DPIs) can deliver higher payloads in less time. However, no data exist assessing DPIs with tracheostomies. OBJECTIVE: The study's aim was to quantify the amount of aerosolized tobramycin delivered to the lungs of in vitro tracheostomized spontaneously breathing pediatric models with the TOBI(r) PodhalerTM (Podhaler) and the PARI LC Plus(r) (LC Plus). METHODS: In vitro tracheostomized models of a 6- and 12-year-old trachea were created. Tobramycin aerosol was delivered to the models using either the LC Plus or Podhaler and captured on a filter at the trachea's distal end. A colorimetric tobramycin assay was used to quantify the amount. Three devices of each type were tested in triplicate to ensure repeatability. RESULTS: A total of 36 runs were completed and showed that the Podhaler was more efficient compared with the LC Plus. Mass and percentage of nominal dose, mean +/- standard deviation (LC Plus vs. Podhaler with single capsule), was 72.4 +/- 11.1 mg (24.1% +/- 3.7%) versus 24.2 +/- 2.4 mg (86.6% +/- 8.7%); p < 0.001. CONCLUSIONS: The study's results show that the Podhaler was significantly more efficient compared with the LC Plus, and three Podhaler capsules delivered approximately the same amount of drug as the Tobramycin inhalation solution. These results suggest that Podhaler's tobramycin delivery is a feasible option in tracheostomized pediatric patients and a clinical study is warranted. PMID- 27563935 TI - Formation of meta-Substituted Phenols by Transition Metal-Free Aromatization: Use of 2-Bromocyclohex-2-en-1-ones. AB - Addition of Grignard or other organometallic reagents to 2-halocyclohex-2-en-1 ones bearing an alkyl or aryl group at C-5, followed by mild acid treatment and exposure to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature, generates meta-substituted phenols in which the newly introduced meta substituent originates from the Grignard reagent. The range of effective organometallic reagents includes alkyl, allyl, alkynyl, aryl, and heteroaryl compounds including those with fluorine substituents. The initial halocyclohexenone can be deprotonated at C-6 and reacted with carbon, fluorine, or sulfur electrophiles before the Grignard addition so as to generate highly substituted phenols. PMID- 27563936 TI - The experience of infertility treatment: the male perspective. AB - Current research surrounding infertility is focused primarily on women alone, thus removing men from the fertility equation. However, alternative research has indicated that, although men also experience infertility, there is a paucity of research on men. Therefore, very little is understood about the experiences of infertility from the male perspective. This study adopted a qualitative approach in an attempt to explore the infertility experience from the perspective of men. Fifteen men who had experienced infertility were interviewed to explore their experiences. Interpretative phenomenological analysis was used to analyse the data. Five superordinate themes were developed, and these included: (1) the influence of society on infertility; (2) feeling unacknowledged; (3) natural verses assisted conception; (4) emotional reactions; and (5) improving the infertility experience. The findings of this research indicated that men experience infertility as a mentally, physically and socially demanding condition. Comparisons to previous research have been made, and future research is proposed. PMID- 27563937 TI - IFNGR2 genetic polymorphism associated with sex-specific paranoid schizophrenia risk. AB - BACKGROUND: Considering current scientific evidence about the significant role of chronic low grade inflammation in the physiopathology of schizophrenia, it has been hypothesized that changes in pro-inflammatory cytokines such as interferon gamma may have a significant role in the predisposition to schizophrenia. AIM: This study focuses on identifying whether the functional polymorphism of interferon gamma receptor 2 (IFNGR2) is a risk factor for the development of schizophrenia. METHODS: This study was conducted by the RFLP-PCR on a Tunisian population composed of 225 patients with different sub-types of schizophrenia and 166 controls. RESULTS: The IFNGR2 (Q64R) polymorphism analysis showed higher frequencies of minor homozygous genotype (RR) and allele (R) in all patients compared to controls (21.8% vs 10.2%; p = .006, OR = 2.54) and (44% vs 34.9%; p = .01; OR = 1.46), respectively. This correlation was confirmed only for males. This study also noted a significant increase of the mutated homozygous (RR) genotype and (R) allele frequencies of IFNGR2 in paranoid schizophrenics compared to controls (31.4% vs 10.2%; p = .001; OR = 3.34 and 47.2% vs 34.9%; p = .009; OR = 1.66, respectively). This increase remains significant after using binary logistic regression to eliminate confounding factors such as age and sex. Additionally, carriers of RR genotype have significant lower scores on the Scale of Assessment of Positive (SAPS) and negative (SANS) symptoms comparatively to the carrier of the QQ + QR genotypes, suggesting that the R recessive allele carriers could have milder symptoms. CONCLUSION: The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia. It is suggested that a chronic neuroinflammation may predispose to the paranoid schizophrenia development in men. PMID- 27563938 TI - From Classical Nonlinear Integrable Systems to Quantum Shortcuts to Adiabaticity. AB - Using shortcuts to adiabaticity, we solve the time-dependent Schrodinger equation that is reduced to a classical nonlinear integrable equation. For a given time dependent Hamiltonian, the counterdiabatic term is introduced to prevent nonadiabatic transitions. Using the fact that the equation for the dynamical invariant is equivalent to the Lax equation in nonlinear integrable systems, we obtain the counterdiabatic term exactly. The counterdiabatic term is available when the corresponding Lax pair exists and the solvable systems are classified in a unified and systematic way. Multisoliton potentials obtained from the Korteweg de Vries equation and isotropic XY spin chains from the Toda equations are studied in detail. PMID- 27563939 TI - Analytic and Nearly Optimal Self-Testing Bounds for the Clauser-Horne-Shimony Holt and Mermin Inequalities. AB - Self-testing refers to the phenomenon that certain extremal quantum correlations (almost) uniquely identify the quantum system under consideration. For instance, observing the maximal violation of the Clauser-Horne-Shimony-Holt (CHSH) inequality certifies that the two parties share a singlet. While self-testing results are known for several classes of states, in many cases they are only applicable if the observed statistics are almost perfect, which makes them unsuitable for practical applications. Practically relevant self-testing bounds are much less common and moreover they all result from a single numerical method (with one exception which we discuss in detail). In this work we present a new technique for proving analytic self-testing bounds of practically relevant robustness. We obtain improved bounds for the case of self-testing the singlet using the CHSH inequality (in particular we show that nontrivial fidelity with the singlet can be achieved as long as the violation exceeds beta^{*}=(16+14sqrt[2])/17~2.11). In the case of self-testing the tripartite Greenberger-Horne-Zeilinger state using the Mermin inequality, we derive a bound which not only improves on previously known results but turns out to be tight. We discuss other scenarios to which our technique can be immediately applied. PMID- 27563940 TI - Exact Short-Time Height Distribution in the One-Dimensional Kardar-Parisi-Zhang Equation and Edge Fermions at High Temperature. AB - We consider the early time regime of the Kardar-Parisi-Zhang (KPZ) equation in 1+1 dimensions in curved (or droplet) geometry. We show that for short time t, the probability distribution P(H,t) of the height H at a given point x takes the scaling form P(H,t)~exp[-Phi_{drop}(H)/sqrt[t]] where the rate function Phi_{drop}(H) is computed exactly for all H. While it is Gaussian in the center, i.e., for small H, the probability distribution function has highly asymmetric non-Gaussian tails that we characterize in detail. This function Phi_{drop}(H) is surprisingly reminiscent of the large deviation function describing the stationary fluctuations of finite-size models belonging to the KPZ universality class. Thanks to a recently discovered connection between the KPZ equation and free fermions, our results have interesting implications for the fluctuations of the rightmost fermion in a harmonic trap at high temperature and the full counting statistics at the edge. PMID- 27563941 TI - Demonstration of Einstein-Podolsky-Rosen Steering Using Single-Photon Path Entanglement and Displacement-Based Detection. AB - We demonstrate the violation of an Einstein-Podolsky-Rosen steering inequality developed for single-photon path entanglement with displacement-based detection. We use a high-rate source of heralded single-photon path-entangled states, combined with high-efficiency superconducting-based detectors, in a scheme that is free of any postselection and thus immune to the detection loophole. This result conclusively demonstrates single-photon entanglement in a one-sided device independent scenario, and opens the way towards implementations of device independent quantum technologies within the paradigm of path entanglement. PMID- 27563942 TI - Foliated Quantum Error-Correcting Codes. AB - We show how to construct a large class of quantum error-correcting codes, known as Calderbank-Steane-Shor codes, from highly entangled cluster states. This becomes a primitive in a protocol that foliates a series of such cluster states into a much larger cluster state, implementing foliated quantum error correction. We exemplify this construction with several familiar quantum error-correction codes and propose a generic method for decoding foliated codes. We numerically evaluate the error-correction performance of a family of finite-rate Calderbank Steane-Shor codes known as turbo codes, finding that they perform well over moderate depth foliations. Foliated codes have applications for quantum repeaters and fault-tolerant measurement-based quantum computation. PMID- 27563943 TI - Entropy Production of Nanosystems with Time Scale Separation. AB - Energy flows in biomolecular motors and machines are vital to their function. Yet experimental observations are often limited to a small subset of variables that participate in energy transport and dissipation. Here we show, through a solvable Langevin model, that the seemingly hidden entropy production is measurable through the violation spectrum of the fluctuation-response relation of a slow observable. For general Markov systems with time scale separation, we prove that the violation spectrum exhibits a characteristic plateau in the intermediate frequency region. Despite its vanishing height, the plateau can account for energy dissipation over a broad time scale. Our findings suggest a general possibility to probe hidden entropy production in nanosystems without direct observation of fast variables. PMID- 27563944 TI - Evading Vacuum Noise: Wigner Projections or Husimi Samples? AB - The accuracy in determining the quantum state of a system depends on the type of measurement performed. Homodyne and heterodyne detection are the two main schemes in continuous-variable quantum information. The former leads to a direct reconstruction of the Wigner function of the state, whereas the latter samples its Husimi Q function. We experimentally demonstrate that heterodyne detection outperforms homodyne detection for almost all Gaussian states, the details of which depend on the squeezing strength and thermal noise. PMID- 27563946 TI - Combined Search for Lorentz Violation in Short-Range Gravity. AB - Short-range experiments testing the gravitational inverse-square law at the submillimeter scale offer uniquely sensitive probes of Lorentz invariance. A combined analysis of results from the short-range gravity experiments HUST-2015, HUST-2011, IU-2012, and IU-2002 permits the first independent measurements of the 14 nonrelativistic coefficients for Lorentz violation in the pure-gravity sector at the level of 10^{-9} m^{2}, improving by an order of magnitude the sensitivity to numerous types of Lorentz violation involving quadratic curvature derivatives and curvature couplings. PMID- 27563945 TI - Characteristics of Four Upward-Pointing Cosmic-Ray-like Events Observed with ANITA. AB - We report on four radio-detected cosmic-ray (CR) or CR-like events observed with the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload. Two of the four were previously identified as stratospheric CR air showers during the ANITA-I flight. A third stratospheric CR was detected during the ANITA-II flight. Here, we report on characteristics of these three unusual CR events, which develop nearly horizontally, 20-30 km above the surface of Earth. In addition, we report on a fourth steeply upward-pointing ANITA-I CR like radio event which has characteristics consistent with a primary that emerged from the surface of the ice. This suggests a possible tau-lepton decay as the origin of this event, but such an interpretation would require significant suppression of the standard model tau-neutrino cross section. PMID- 27563947 TI - Satellite Test of the Equivalence Principle as a Probe of Modified Newtonian Dynamics. AB - The proposed satellite test of the equivalence principle (STEP) will detect possible violations of the weak equivalence principle by measuring relative accelerations between test masses of different composition with a precision of one part in 10^{18}. A serendipitous by-product of the experimental design is that the absolute or common-mode acceleration of the test masses is also measured to high precision as they oscillate along a common axis under the influence of restoring forces produced by the position sensor currents, which in drag-free mode lead to Newtonian accelerations as small as 10^{-14} g. This is deep inside the low-acceleration regime where modified Newtonian dynamics (MOND) diverges strongly from the Newtonian limit of general relativity. We show that MOND theories (including those based on the widely used "n family" of interpolating functions as well as the covariant tensor-vector-scalar formulation) predict an easily detectable increase in the frequency of oscillations of the STEP test masses if the strong equivalence principle holds. If it does not hold, MOND predicts a cumulative increase in oscillation amplitude which is also detectable. STEP thus provides a new and potentially decisive test of Newton's law of inertia, as well as the equivalence principle in both its strong and weak forms. PMID- 27563948 TI - Consistent Perturbative Fixed Point Calculations in QCD and Supersymmetric QCD. AB - We suggest how to consistently calculate the anomalous dimension gamma_{*} of the psi[over -]psi operator in finite order perturbation theory at an infrared fixed point for asymptotically free theories. If the n+1 loop beta function and n loop anomalous dimension are known, then gamma_{*} can be calculated exactly and fully scheme independently in a Banks-Zaks expansion through O(Delta_{f}^{n}), where Delta_{f}=N[over -]_{f}-N_{f}, N_{f} is the number of flavors, and N[over -]_{f} is the number of flavors above which asymptotic freedom is lost. For a supersymmetric theory, the calculation preserves supersymmetry order by order in Delta_{f}. We then compute gamma_{*} through O(Delta_{f}^{2}) for supersymmetric QCD in the dimensional reduction scheme and find that it matches the exact known result. We find that gamma_{*} is astonishingly well described in perturbation theory already at the few loops level throughout the entire conformal window. We finally compute gamma_{*} through O(Delta_{f}^{3}) for QCD and a variety of other nonsupersymmetric fermionic gauge theories. Small values of gamma_{*} are observed for a large range of flavors. PMID- 27563949 TI - Superintegrability of d-Dimensional Conformal Blocks. AB - We observe that conformal blocks of scalar four-point functions in a d dimensional conformal field theory can be mapped to eigenfunctions of a two particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions. We conclude with a short outlook, in particular, on the consequences of integrability for the theory of conformal blocks. PMID- 27563951 TI - Impact of Nonstandard Interactions on Sterile-Neutrino Searches at IceCube. AB - We analyze the energy and zenith angle distributions of the latest two-year IceCube data set of upward-going atmospheric neutrinos to constrain sterile neutrinos at the eV scale in the 3+1 scenario. We find that the parameters favored by a combination of LSND and MiniBooNE data are excluded at more than the 99% C.L. We explore the impact of nonstandard matter interactions on this exclusion and find that the exclusion holds for nonstandard interactions (NSIs) that are within the stringent model-dependent bounds set by collider and neutrino scattering experiments. However, for large NSI parameters subject only to model independent bounds from neutrino oscillation experiments, the LSND and MiniBooNE data are consistent with IceCube. PMID- 27563952 TI - Protophobic Fifth-Force Interpretation of the Observed Anomaly in ^{8}Be Nuclear Transitions. AB - Recently a 6.8sigma anomaly has been reported in the opening angle and invariant mass distributions of e^{+}e^{-} pairs produced in ^{8}Be nuclear transitions. The data are explained by a 17 MeV vector gauge boson X that is produced in the decay of an excited state to the ground state, ^{8}Be^{*}->^{8}Be X, and then decays through X->e^{+}e^{-}. The X boson mediates a fifth force with a characteristic range of 12 fm and has millicharged couplings to up and down quarks and electrons, and a proton coupling that is suppressed relative to neutrons. The protophobic X boson may also alleviate the current 3.6sigma discrepancy between the predicted and measured values of the muon's anomalous magnetic moment. PMID- 27563953 TI - Vector-Boson Fusion Higgs Production at Three Loops in QCD. AB - We calculate the next-to-next-to-next-to-leading-order (N^{3}LO) QCD corrections to inclusive vector-boson fusion Higgs production at proton colliders, in the limit in which there is no color exchange between the hadronic systems associated with the two colliding protons. We also provide differential cross sections for the Higgs transverse momentum and rapidity distributions. We find that the corrections are at the 10/00-20/00 level, well within the scale uncertainty of the next-to-next-to-leading-order calculation. The associated scale uncertainty of the N^{3}LO calculation is typically found to be below the 20/00 level. We also consider theoretical uncertainties due to missing higher order parton distribution functions, and provide an estimate of their importance. PMID- 27563954 TI - Massive Photons: An Infrared Regularization Scheme for Lattice QCD+QED. AB - Standard methods for including electromagnetic interactions in lattice quantum chromodynamics calculations result in power-law finite-volume corrections to physical quantities. Removing these by extrapolation requires costly computations at multiple volumes. We introduce a photon mass to alternatively regulate the infrared, and rely on effective field theory to remove its unphysical effects. Electromagnetic modifications to the hadron spectrum are reliably estimated with a precision and cost comparable to conventional approaches that utilize multiple larger volumes. A significant overall cost advantage emerges when accounting for ensemble generation. The proposed method may benefit lattice calculations involving multiple charged hadrons, as well as quantum many-body computations with long-range Coulomb interactions. PMID- 27563955 TI - Enhancing the Effect of Lorentz Invariance and Einstein's Equivalence Principle Violation in Nuclei and Atoms. AB - Local Lorentz invariance violating (LLIV) and Einstein equivalence principle violating (EEPV) effects in atomic experiments are discussed. The EEPV effects are strongly enhanced in the narrow 7.8 eV transition in the _{90}^{229}Th nucleus. The nuclear LLIV tensors describing the anisotropy in the maximal attainable speed for massive particles (analog of the Michelson-Morley experiment for light) are expressed in terms of the experimental values of the nuclear quadrupole moments. Calculations for nuclei of experimental interest _{55}^{133}Cs, _{37}^{85}Rb, _{37}^{87}Rb, _{80}^{201}Hg, _{54}^{131}Xe, and _{10}^{21}Ne are performed. The results for _{10}^{21}Ne are used to improve the limits on the proton LLIV interaction constants by 4 orders of magnitude. PMID- 27563956 TI - Accurate Semilocal Density Functional for Condensed-Matter Physics and Quantum Chemistry. AB - Most density functionals have been developed by imposing the known exact constraints on the exchange-correlation energy, or by a fit to a set of properties of selected systems, or by both. However, accurate modeling of the conventional exchange hole presents a great challenge, due to the delocalization of the hole. Making use of the property that the hole can be made localized under a general coordinate transformation, here we derive an exchange hole from the density matrix expansion, while the correlation part is obtained by imposing the low-density limit constraint. From the hole, a semilocal exchange-correlation functional is calculated. Our comprehensive test shows that this functional can achieve remarkable accuracy for diverse properties of molecules, solids, and solid surfaces, substantially improving upon the nonempirical functionals proposed in recent years. Accurate semilocal functionals based on their associated holes are physically appealing and practically useful for developing nonlocal functionals. PMID- 27563957 TI - Superradiance in a Large and Dilute Cloud of Cold Atoms in the Linear-Optics Regime. AB - Superradiance has been extensively studied in the 1970s and 1980s in the regime of superfluorescence, where a large number of atoms are initially excited. Cooperative scattering in the linear-optics regime, or "single-photon superradiance," has been investigated much more recently, and superradiant decay has also been predicted, even for a spherical sample of large extent and low density, where the distance between atoms is much larger than the wavelength. Here, we demonstrate this effect experimentally by directly measuring the decay rate of the off-axis fluorescence of a large and dilute cloud of cold rubidium atoms after the sudden switch off of a low-intensity laser driving the atomic transition. We show that, at large detuning, the decay rate increases with the on resonance optical depth. In contrast to forward scattering, the superradiant decay of off-axis fluorescence is suppressed near resonance due to attenuation and multiple-scattering effects. PMID- 27563958 TI - Observation of Single-Photon Superradiance and the Cooperative Lamb Shift in an Extended Sample of Cold Atoms. AB - We report direct, time-resolved observations of single-photon superradiance in a highly extended, elliptical sample of cold ^{87}Rb atoms. The observed rapid decay rate is accompanied by its counterpart, the cooperative Lamb shift. The rate of the strongly directional decay, and the associated shift, scale linearly with the number of atoms, demonstrating the collective nature of the observed quantities. PMID- 27563960 TI - Electrostatically Guided Rydberg Positronium. AB - We report experiments in which positronium (Ps) atoms were guided using inhomogeneous electric fields. Ps atoms in Rydberg-Stark states with principal quantum number n=10 and electric dipole moments up to 610 D were prepared via two color two-photon optical excitation in the presence of a 670 V cm^{-1} electric field. The Ps atoms were created at the entrance of a 0.4 m long electrostatic quadrupole guide, and were detected at the end of the guide via annihilation gamma radiation. When the lasers were tuned to excite low-field-seeking Stark states, a fivefold increase in the number of atoms reaching the end of the guide was observed, whereas no signal was detected when high-field-seeking states were produced. The data are consistent with the calculated geometrical guide acceptance. PMID- 27563959 TI - Determination of Energy-Transfer Distributions in Ionizing Ion-Molecule Collisions. AB - The ionization and fragmentation of the nucleoside thymidine in the gas phase has been investigated by combining ion collision with state-selected photoionization experiments and quantum chemistry calculations. The comparison between the mass spectra measured in both types of experiments allows us to accurately determine the distribution of the energy deposited in the ionized molecule as a result of the collision. The relation of two experimental techniques and theory shows a strong correlation between the excited states of the ionized molecule with the computed dissociation pathways, as well as with charge localization or delocalization. PMID- 27563961 TI - Genuine Quantum Signatures in Synchronization of Anharmonic Self-Oscillators. AB - We study the synchronization of a Van der Pol self-oscillator with Kerr anharmonicity to an external drive. We demonstrate that the anharmonic, discrete energy spectrum of the quantum oscillator leads to multiple resonances in both phase locking and frequency entrainment not present in the corresponding classical system. Strong driving close to these resonances leads to nonclassical steady-state Wigner distributions. Experimental realizations of these genuine quantum signatures can be implemented with current technology. PMID- 27563962 TI - Observation of Nondegenerate Two-Photon Gain in GaAs. AB - Two-photon lasers require materials with large two-photon gain (2PG) coefficients and low linear and nonlinear losses. Our previous demonstration of large enhancement of two-photon absorption in semiconductors for very different photon energies translates directly into enhancement of 2PG. We experimentally demonstrate nondegenerate 2PG in optically excited bulk GaAs via femtosecond pump probe measurements. 2PG is isolated from other pump induced effects through the difference between measurements performed with parallel and perpendicular polarizations of pump and probe. An enhancement in the 2PG coefficient of nearly 2 orders of magnitude is reported. The results point a possible way toward two photon semiconductor lasers. PMID- 27563950 TI - Searches for Sterile Neutrinos with the IceCube Detector. AB - The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous nu_{MU} or nu[over -]_{MU} disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3+1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin^{2}2theta_{24}<=0.02 at Deltam^{2}~0.3 eV^{2} at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of |U_{e4}|^{2}. PMID- 27563963 TI - Phonon-Mediated Nonclassical Interference in Diamond. AB - Quantum interference of single photons is a fundamental aspect of many photonic quantum processing and communication protocols. Interference requires that the multiple pathways through an interferometer be temporally indistinguishable to within the coherence time of the photon. In this Letter, we use a diamond quantum memory to demonstrate interference between quantum pathways, initially temporally separated by many multiples of the optical coherence time. The quantum memory can be viewed as a light-matter beam splitter, mapping a THz-bandwidth single photon to a variable superposition of the output optical mode and stored phononic mode. Because the memory acts both as a beam splitter and as a buffer, the relevant coherence time for interference is not that of the photon, but rather that of the memory. We use this mechanism to demonstrate nonclassical single-photon and two photon interference between quantum pathways initially separated by several picoseconds, even though the duration of the photons themselves is just ~250 fs. PMID- 27563964 TI - Preparation of Ultracold Atom Clouds at the Shot Noise Level. AB - We prepare number stabilized ultracold atom clouds through the real-time analysis of nondestructive images and the application of feedback. In our experiments, the atom number N~10^{6} is determined by high precision Faraday imaging with uncertainty DeltaN below the shot noise level, i.e., DeltaN